PMID- 10059355
TI  - Nonlinear bubble dynamics in a slowly driven foam.

PMID- 10059356
TI  - Analytical study of time series generation by feed-forward networks.

PMID- 10059358
TI  - Stationary striations developed in the ionospheric modification.

PMID- 10059357
TI  - Cooperative molecular motors.

PMID- 10059359
TI  - Comment on "Superinstantons and the reliability of perturbation theory in non
      Abelian models"

PMID- 10059361
TI  - Comment on "Observation of oscillatory magnetic order in the antiferromagnetic
      superconductor HoNi2Ba2C"

PMID- 10059360
TI  - Patrascioiu and Seiler reply.

PMID- 10059362
TI  - Grigereit et al. reply.

PMID- 10059366
TI  - Atom wave interferometry with diffraction gratings of light.

PMID- 10059368
TI  - Doppler peaks from cosmic texture.

PMID- 10059367
TI  - Atom interferometer based on Bragg scattering from standing light waves.

PMID- 10059369
TI  - Making ends meet: String unification and low-energy data.

PMID- 10059370
TI  - Candidate events in a search for nu -bar micro--> nu -bare oscillations.

PMID- 10059371
TI  - An alternative analysis of the LSND neutrino oscillation search data on nu -bar
      micro--> nu -bare.

PMID- 10059372
TI  - Search for narrow sum-energy lines in electron-positron pair emission from heavy
      ion collisions near the Coulomb barrier.

PMID- 10059373
TI  - Radial flow in Au+Au collisions at E=(0.25-1.15)A GeV.

PMID- 10059375
TI  - Shattering of clusters upon surface impact: An experimental and theoretical
      study.

PMID- 10059374
TI  - Direct observation of s-wave atomic collisions.

PMID- 10059376
TI  - Observation of visible and infrared luminescence of xenon cluster ions: Role of
      radiative processes in the formation of cluster ions and their size and
      temperature dependence.

PMID- 10059377
TI  - Photonic-wire laser.

PMID- 10059379
TI  - Effect of an insoluble surfactant on capillary oscillations of bubbles in water:
      Observation of a maximum in the damping.

PMID- 10059378
TI  - Ray chaos and Q spoiling in lasing droplets.

PMID- 10059380
TI  - Viscous effects on inertial range scalings in a dynamical model of turbulence.

PMID- 10059381
TI  - Self-consistent treatment of repulsive and attractive forces in nonuniform
      liquids.

PMID- 10059382
TI  - Stick-slip transition at polymer melt/solid interfaces.

PMID- 10059383
TI  - Negative diffusion and clustering of growing particles.

PMID- 10059385
TI  - Scaling of the specific heat in superfluid films.

PMID- 10059384
TI  - Nonuniversal dynamical crossover in pure and binary fluids near a critical point.

PMID- 10059387
TI  - Six-dimensional quantum dynamics of adsorption and desorption of H2 at Pd(100):
      Steering and steric effects.

PMID- 10059386
TI  - Numerical evidence for bcc ordering at the surface of a critical fcc nucleus.

PMID- 10059388
TI  - Self-organized critical and synchronized states in a nonequilibrium percolation
      model.

PMID- 10059389
TI  - Template structure at the silicon/amorphous-silicide interface.

PMID- 10059390
TI  - Step-bunching instability of vicinal surfaces under stress.

PMID- 10059392
TI  - Atomic size effects in pressure-induced amorphization of a binary covalent
      lattice.

PMID- 10059391
TI  - Theory of nickel and nickel-hydrogen complexes in silicon.

PMID- 10059393
TI  - Surfactant mediated crystal growth of semiconductors.

PMID- 10059394
TI  - Longer living majority than minority image state at Fe(110).

PMID- 10059395
TI  - Semiclassical analysis of the conductance of mesoscopic systems.

PMID- 10059396
TI  - Direct vortex lattice imaging and tunneling spectroscopy of flux lines on
      YBa2Cu3O7- delta.

PMID- 10059397
TI  - Two phase transitions in the fully frustrated XY model.

PMID- 10059398
TI  - Self-similarity and localization.

PMID- 10059399
TI  - Microscopic model of nonreciprocal optical effects in Cr2O3.

PMID- 10059400
TI  - Linear viscoelasticity of colloidal hard sphere suspensions near the glass
      transition.

PMID- 10059401
TI  - Mechanisms of protein crystal growth: An atomic force microscopy study of
      canavalin crystallization.

PMID- 10059402
TI  - Investigation of virus crystal growth mechanisms by in situ atomic force
      microscopy.

PMID- 10059403
TI  - Controlling nonchaotic neuronal noise using chaos control techniques.

PMID- 10059405
TI  - Convergent strong-coupling expansions from divergent weak-coupling perturbation
      theory.

PMID- 10059407
TI  - Does the time-of-swing method give a correct value of the newtonian gravitational
      constant?

PMID- 10059406
TI  - Invaded cluster algorithm for equilibrium critical points.

PMID- 10059408
TI  - CP violating metastable states and baryogenesis in the hot standard model.

PMID- 10059410
TI  - New method for determining ||Vub||/||Vts|| by the processes B-bar--> rho l nu 
      bar and B-bar-->K*ll-bar.

PMID- 10059411
TI  - Soft photons from off-shell particles in a hot plasma.

PMID- 10059409
TI  - New measurement of the CP violation parameter eta +- gamma.

PMID- 10059412
TI  - Coherent control of isotope separation in HD+ photodissociation by strong fields.

PMID- 10059413
TI  - Role of electron localization in intense-field molecular ionization.

PMID- 10059414
TI  - Bragg scattering from atoms in optical lattices.

PMID- 10059415
TI  - Aggregation, fragmentation, and the nonlinear dynamics of electrorheological
      fluids in oscillatory shear.

PMID- 10059416
TI  - Stationary shear flow in boundary driven Hamiltonian systems.

PMID- 10059417
TI  - Stability of a uniform-density breathing beam with circular cross section.

PMID- 10059418
TI  - Cold kilo-electron ball as probe for charge-proportional cyclotron frequency
      shift in Penning trap cavity.

PMID- 10059419
TI  - Evidence for a pronounced local orientational order in the high temperature phase
      of C60.

PMID- 10059420
TI  - Structural glass transition and the entropy of the metastable states.

PMID- 10059421
TI  - Rate memory of structural relaxation in glasses and its detection by
      multidimensional NMR.

PMID- 10059422
TI  - Proton and deuteron field-cycling NMR relaxometry of liquids in porous glasses:
      Evidence for Levy-walk statistics.

PMID- 10059423
TI  - In-plane lattice reconstruction of Cu(100).

PMID- 10059424
TI  - Density Profile of Polyelectrolyte Brushes.

PMID- 10059425
TI  - Order-N multiple scattering approach to electronic structure calculations.

PMID- 10059426
TI  - Total energy calculation of the magnetocrystalline anisotropy energy in the
      ferromagnetic 3d metals.

PMID- 10059427
TI  - Precursors and transition to chaos in a quantum well in a tilted magnetic field.

PMID- 10059428
TI  - Pair tunneling in semiconductor quantum dots.

PMID- 10059430
TI  - Monte Carlo simulation of the ferromagnetic order-disorder transition in a
      Heisenberg fluid.

PMID- 10059429
TI  - Photoelectron diffraction in magnetic linear dichroism.

PMID- 10059431
TI  - Heterogeneous catalysis on a disordered surface.

PMID- 10059432
TI  - Tracking unstable turing patterns through mixed-mode spatiotemporal chaos.

PMID- 10059433
TI  - Cooperative formation of chiral patterns during growth of bacterial colonies.

PMID- 10059434
TI  - Comment on "Role of a new type of correlated disorder in extended electronic
      states in the Thue-Morse lattice"

PMID- 10059435
TI  - Transmission through organic thin films.

PMID- 10059436
TI  - Kadyshevitch and Naaman reply.

PMID- 10059437
TI  - Comment on "Pressure-induced structural metastability in crystalline C60".

PMID- 10059441
TI  - Velocity peaks in the cold dark matter spectrum on Earth.

PMID- 10059438
TI  - Wolk, Horoyski, and Thewalt reply.

PMID- 10059443
TI  - Intermediate-mass fragment decay of the neck zone formed in peripheral
      209Bi+136Xe collisions at Elab/A=28MeV.

PMID- 10059442
TI  - Understanding proton emission in central heavy-ion collisions.

PMID- 10059444
TI  - Resonant two-photon detachment through the lowest singlet D state in H-

PMID- 10059445
TI  - Semiclassical quantization of intermittency in helium.

PMID- 10059446
TI  - Reconstruction of the quantum mechanical state of a trapped ion.

PMID- 10059448
TI  - Pressure broadening of gas phase molecular at very low temperature.

PMID- 10059447
TI  - Evidence for a molecule-rotation-dependent spin polarization transfer mechanism
      in the photon-induced autoionization of HCl and DCl.

PMID- 10059449
TI  - Optimal quantum measurements for phase estimation.

PMID- 10059451
TI  - Controlling chaos using differential geometric method.

PMID- 10059450
TI  - Finding regular orbits.

PMID- 10059452
TI  - Model for plane turbulent Couette flow.

PMID- 10059454
TI  - Atom condensation on surface clusters: Adsorption or incorporation?

PMID- 10059453
TI  - Tunneling spectroscopy of bcc (001) surface states.

PMID- 10059455
TI  - Spontaneous ordering of arrays of coherent strained islands.

PMID- 10059456
TI  - Free-running droplets.

PMID- 10059457
TI  - Direct observation of a new growth mode: Subsurface island growth of Cu on
      Pb(111).

PMID- 10059458
TI  - Kinetic anisotropy and dendritic growth in electrochemical deposition.

PMID- 10059459
TI  - Hot electrons in amorphous silicon.

PMID- 10059461
TI  - Peak effect in twinned superconductors.

PMID- 10059460
TI  - Apparent inconsistency of observed composite Fermion geometric resonances and
      measured effective mass.

PMID- 10059462
TI  - Ab initio calculations of the giant magnetoresistance.

PMID- 10059464
TI  - Nonreciprocal optical rotation in antiferromagnets.

PMID- 10059463
TI  - Origin of pure spin superradiance.

PMID- 10059465
TI  - Evidence of quantum correlation effects of protons and deuterons in the Raman
      spectra of liquid H2O-D2O.

PMID- 10059467
TI  - Dynamics of a meandering river.

PMID- 10059466
TI  - Real space measurement of structure in phase separating binary fluid mixtures.

PMID- 10059468
TI  - Comment on "Reduced dynamics need not be completely positive"

PMID- 10059469
TI  - Pechukas replies.

PMID- 10059470
TI  - Photoproduction of eta mesons near threshold.

PMID- 10059471
TI  - Krusche et al. reply.

PMID- 10059472
TI  - Comment on "Piezophotonic switching due to local field effects in a coherently
      prepared medium of three-level atoms"

PMID- 10059473
TI  - Manka et al. reply.

PMID- 10059474
TI  - Comment on "Magnetoresistance associated with antiferromagnetic interlayer
      coupling spaced by a semiconductor in Fe/Si multilayers"

PMID- 10059477
TI  - Kink drift motion in the Phi 4 model.

PMID- 10059478
TI  - Complementarity and the quantum eraser.

PMID- 10059479
TI  - Properties of consistent histories.

PMID- 10059480
TI  - Restoration of isotropy on fractals.

PMID- 10059481
TI  - General relativistic gravitational field of a rigidly rotating disk of dust:
      solution in terms of ultraelliptic functions.

PMID- 10059482
TI  - Volume operator in discretized quantum gravity.

PMID- 10059483
TI  - Origin of the high energy extragalactic diffuse gamma ray background.

PMID- 10059485
TI  - Gauge invariance and unstable particles.

PMID- 10059484
TI  - Arrival directions of the most energetic cosmic rays.

PMID- 10059486
TI  - A method for determining the CP violating phase gamma.

PMID- 10059487
TI  - Measurement of the polarization in the decays Bd-->J/ psi K*0 and Bs-->J/ psi
      phi.

PMID- 10059488
TI  - Analyzing power measurement in inclusive Lambda 0 production with a 200 GeV/c
      polarized proton beam.

PMID- 10059489
TI  - Search for new metastable particles produced in Au+Au collisions at 10.8A GeV/c.

PMID- 10059491
TI  - Universality of symmetry and mixed-symmetry collective nuclear states.

PMID- 10059490
TI  - Time relationships between direct particle emission and fragmentation: A probe
      for nuclear expansion prior to fragment freeze-out.

PMID- 10059493
TI  - Intercollisional interference effect in the light scattering spectrum of xenon
      gas.

PMID- 10059492
TI  - Effective charges and octupole collectivity in the 132Sn region.

PMID- 10059494
TI  - Molecular lifetime changes induced by nanometer scale optical fields.

PMID- 10059496
TI  - Acoustic transmission spectra in the Penrose lattice.

PMID- 10059495
TI  - Experimental demonstration of high-efficiency cyclotron-autoresonance-maser
      operation.

PMID- 10059497
TI  - Experimental evidence for differences in the extended self-similarity scaling
      laws between fluid and magnetohydrodynamic turbulent flows.

PMID- 10059499
TI  - Experimental evidence for chaotic transport in a positron trap.

PMID- 10059498
TI  - Persistent small scale anisotropy in homogeneous shear flows.

PMID- 10059500
TI  - Strong x-ray emission from high-temperature plasmas produced by intense
      irradiation of clusters.

PMID- 10059501
TI  - Novel spectroscopic method for analysis of nonthermal electric fields in plasmas.

PMID- 10059503
TI  - 2D coarsening in phase-separated polymer solutions: Dependence on distance from
      criticality.

PMID- 10059504
TI  - Dynamics and morphology of brittle cracks: A molecular-dynamics study of silicon
      nitride.

PMID- 10059502
TI  - Areal density measurement of imploded cryogenic target by energy peak shift of DD
      produced protons.

PMID- 10059505
TI  - Site occupation reversal in the Fe-Cr sigma phase.

PMID- 10059507
TI  - Cavitation versus vortex nucleation in a superfluid model.

PMID- 10059506
TI  - Nature of crossover between ising-like and mean-field critical behavior in fluids
      and fluid mixtures.

PMID- 10059508
TI  - Solvent effects on the monolayer structure of long n-alkane molecules adsorbed on
      graphite.

PMID- 10059509
TI  - Diffusion of clusters of atoms and vacancies on surfaces and the dynamics of
      diffusion-driven coarsening.

PMID- 10059510
TI  - Ising-like description of structurally relaxed ordered and disordered alloys.

PMID- 10059511
TI  - First-principles study of excitonic self-trapping in diamond.

PMID- 10059512
TI  - Influence of s-d exchange interaction on universal conductance fluctuations in
      Cd1-xMnxTe:In.

PMID- 10059514
TI  - Direct numerical experiment on two-dimensional pinning dynamics of a three
      dimensional vortex line in layered superconductors.

PMID- 10059513
TI  - Observation of midgap interface states in buried metal/GaAs junctions.

PMID- 10059515
TI  - X-ray magnetic scattering from nonmagnetic Lu in a DyLu alloy.

PMID- 10059516
TI  - Quadrupolar effect in X-ray magnetic circular dichroism.

PMID- 10059517
TI  - Dephasing and bursting in coupled neural oscillators.

PMID- 10059518
TI  - Comment on "Superluminality, parelectricity, and Earnshaw's theorem in media with
      inverted populations"

PMID- 10059519
TI  - Comment on "Stopping power theory for screened Coulomb binary collisions in a
      nondegenerate plasma"

PMID- 10059521
TI  - Comment on "Radiation-induced Tc reduction and pair breaking in High-Tc
      superconductors"

PMID- 10059520
TI  - Ordonez and Molina reply.

PMID- 10059523
TI  - Jackson et al. reply.

PMID- 10059524
TI  - Comment on "Attractive potential between confined colloids at low ionic strength"

PMID- 10059522
TI  - Comment on "Radiation-induced Tc reduction and pair breaking in high-Tc
      superconductors"

PMID- 10059525
TI  - Reconstructing the density operator via simple projectors.

PMID- 10059526
TI  - Multiphoton exchange amplitudes observed by neutron interferometry.

PMID- 10059527
TI  - Universality in random-walk models with birth and death.

PMID- 10059529
TI  - Warm inflation.

PMID- 10059528
TI  - Choptuik spacetime as an eigenvalue problem.

PMID- 10059530
TI  - Proposal to search for a monochromatic component of solar axions using 57Fe.

PMID- 10059533
TI  - Anomalous structure in the beta decay of gaseous molecular tritium.

PMID- 10059531
TI  - Study of the strong coupling constant using W+jet processes.

PMID- 10059532
TI  - Observation of the isospin-violating decay Ds*+-->D+s pi 0.

PMID- 10059534
TI  - Neutron skin of Na isotopes studied via their interaction cross sections.

PMID- 10059535
TI  - Strong interaction shift and width of the 1s level in pionic hydrogen.

PMID- 10059536
TI  - Precision separated-oscillatory-field measurement of the n=10 F3-+G4 interval in
      helium: A precision test of long-range relativistic, radiative, and retardation
      effects.

PMID- 10059537
TI  - Laser-guided atoms in hollow-core optical fibers.

PMID- 10059539
TI  - Kinetic energy distribution of H(2p) atoms from dissociative excitation of H2.

PMID- 10059538
TI  - Combined trap with the potential for antihydrogen production.

PMID- 10059540
TI  - Yoked superfluorescence.

PMID- 10059541
TI  - Dynamical behavior of a dissipative particle in a periodic potential subject to
      chaotic noise: Retrieval of chaotic determinism with broken parity.

PMID- 10059542
TI  - Domain walls in wave patterns.

PMID- 10059543
TI  - Relaxation of 2D turbulence to vortex crystals.

PMID- 10059544
TI  - An invariant measure of disorder in patterns.

PMID- 10059545
TI  - Sheared flow stabilization of the m=1 kink mode in Z pinches.

PMID- 10059546
TI  - Crystallization of molecular liquids in computer simulations: Carbon dioxide.

PMID- 10059547
TI  - What forces bind liquid crystals?

PMID- 10059548
TI  - New features of two-dimensional soft matter domains: Dips and quasicusps.

PMID- 10059550
TI  - Overshooting effects in nonequilibrium ordering dynamics.

PMID- 10059549
TI  - Cluster irradiation of multilayers: Mixing by electronic energy deposition.

PMID- 10059551
TI  - Rotating frame nuclear magnetic relaxation in TlH2AsO4.

PMID- 10059552
TI  - Polarizable quantum systems in crossed electric and magnetic fields.

PMID- 10059554
TI  - Phase diagram of vortices in superfluid 3He-A.

PMID- 10059553
TI  - Low damping of micron capillary waves on superfluid 4He.

PMID- 10059555
TI  - Observation of a new surface state on 4He crystal interfaces.

PMID- 10059557
TI  - Time-resolved cuspidal structure in the wave front of surface acoustic pulses on
      (111) gallium arsenide.

PMID- 10059556
TI  - Chemical potential maps and spatial correlations in 2D-island ripening on
      Si(001).

PMID- 10059558
TI  - Low temperature magnetoresistance and the magnetic phase diagram of La1-xCaxMnO3.

PMID- 10059559
TI  - Temporal correlation of electrons: Suppression of shot noise in a ballistic
      quantum point contact.

PMID- 10059560
TI  - Dynamical simulation of transport in one-dimensional quantum wires.

PMID- 10059561
TI  - Quantum Monte Carlo approach to elementary excitations of antiferromagnetic
      Heisenberg chains.

PMID- 10059562
TI  - Low-energy yield spectroscopy as a novel technique for determining band offsets:
      Application to the c-Si(100)/a-Si:H-heterostructure.

PMID- 10059563
TI  - Local unbinding of pinched membranes.

PMID- 10059564
TI  - Spinodal fluctuations of budding vesicles.

PMID- 10059565
TI  - Depletion forces in the presence of electrostatic double layer repulsion.

PMID- 10059566
TI  - Feedback-controlled dynamics of meandering spiral waves.

PMID- 10059567
TI  - Translational order and neutron diffraction studies of magnetic flux lattices.

PMID- 10059568
TI  - Yaron et al. reply.

PMID- 10059571
TI  - Einstein and Yang-Mills theories in hyperbolic form without gauge fixing.

PMID- 10059573
TI  - Pair creation of black holes joined by cosmic strings.

PMID- 10059572
TI  - Pair production of black holes on cosmic strings.

PMID- 10059574
TI  - Breaking cosmic strings without monopoles.

PMID- 10059575
TI  - QCD corrections from the top quark to relations between electroweak parameters up
      to order alpha 2s.

PMID- 10059576
TI  - Delta I=4 fifurcation without explicit fourfold symmetry.

PMID- 10059577
TI  - Absolute calibration of electric fields using Stark spectroscopy.

PMID- 10059578
TI  - Problems with the standard semiclassical impact line-broadening theory.

PMID- 10059579
TI  - Selective excitation of vibrational wave packet motion using chirped pulses.

PMID- 10059580
TI  - Low energy (<5 eV) F+ and F- ion transmission through condensed layers of water:
      Enhancement and attenuation processes.

PMID- 10059581
TI  - Observation of structure in differential transfer ionization of argon atoms by
      positrons.

PMID- 10059582
TI  - Quantum nondemolition demonstration via repeated backaction evading measurements.

PMID- 10059583
TI  - Nonclassical excitation for atoms in a squeezed vacuum.

PMID- 10059584
TI  - Optical "multiexcitons": Quantum gap solitons in nonlinear Bragg reflectors.

PMID- 10059585
TI  - Universal behavior of Lyapunov exponents in unstable systems.

PMID- 10059586
TI  - Power law wave-number spectra of scum on the surface of a flowing fluid.

PMID- 10059587
TI  - Transport properties of random media: A new effective medium theory.

PMID- 10059588
TI  - Atomic interferometry with the micromaser.

PMID- 10059589
TI  - Transition between positive and negative hexagons in optical pattern formation.

PMID- 10059590
TI  - Lateral capillary forces measured by torsion microbalance.

PMID- 10059592
TI  - Elastic isotropy and anisotropy in quasicrystalline and cubic AlCuLi.

PMID- 10059591
TI  - Breaking of rotational symmetry during decomposition of elastically anisotropic
      alloys.

PMID- 10059593
TI  - Crystallization of opals from polydisperse nanoparticles.

PMID- 10059594
TI  - Yield strength of diamond.

PMID- 10059595
TI  - Theoretical confirmation of the high pressure simple cubic phase in calcium.

PMID- 10059596
TI  - One-stage continuous melting transition in two dimensions.

PMID- 10059597
TI  - Entropic expulsion in vesicles.

PMID- 10059598
TI  - Commensurate and incommensurate phases at reconstructed (In,Ga)As(001) surfaces:
      x-ray diffraction evidence for a composition lock-in.

PMID- 10059599
TI  - Quasiparticle band structure of CdS.

PMID- 10059600
TI  - Adaptive renormalization group approach to electron correlations.

PMID- 10059601
TI  - Spectral weight transfer of the optical conductivity in doped Mott insulators.

PMID- 10059602
TI  - Hidden Breit-Wigner distribution and other properties of random matrices with
      preferential basis.

PMID- 10059603
TI  - Friedel oscillations for interacting fermions in one dimension.

PMID- 10059604
TI  - Continuum quantum ferromagnets at finite temperature and the quantum Hall effect.

PMID- 10059605
TI  - Single domain switching investigated using telegraph noise spectroscopy: possible
      evidence for macroscopic quantum tunneling.

PMID- 10059606
TI  - Oblique confinement and phase transitions in Chern-Simons gauge theories.

PMID- 10059607
TI  - Vortex-motion-induced voltage noise in YBa2Cu3O7- delta single crystals.

PMID- 10059608
TI  - Direct shear probe of vortex lattice melting in Bi2Sr2CaCu2O8 single crystals.

PMID- 10059609
TI  - Quasiparticle mean free path in YBa2Cu3O7 measured by the thermal Hall
      conductivity.

PMID- 10059611
TI  - Thermodynamic limit of density matrix renormalization.

PMID- 10059610
TI  - Observation of maximum supercurrent quantization in a superconducting quantum
      point contact.

PMID- 10059612
TI  - Large magnetovolume effect in yttrium doped La-Ca-Mn-O perovskite.

PMID- 10059614
TI  - Observation of isotope effects in sonoluminescence.

PMID- 10059613
TI  - Determination of the nuclear quadrupole moment of 57Fe.

PMID- 10059615
TI  - Band effect on inelastic rare gas collisions with solid surfaces.

PMID- 10059616
TI  - Growth and structure of random fibre clusters and cluster networks.

PMID- 10059618
TI  - Delay-induced chaos in catalytic surface reactions: NO reduction on Pt(100).

PMID- 10059617
TI  - Observation of front bifurcations in controlled geometries: From one to two
      dimensions.

PMID- 10059619
TI  - Effect of the Condensed Phase on Dissociative Electron Attachment: CH3Cl
      Condensed on a Kr Surface.

PMID- 10059620
TI  - Observation of accelerated nucleation in dense colloidal fluids of hard sphere
      particles.

PMID- 10059622
TI  - Comment on "Acoustic band structure of periodic elastic composites"

PMID- 10059621
TI  - Correlation between shear viscosity and anisotropic domain growth during spinodal
      decomposition under shear flow.

PMID- 10059623
TI  - Kushwaha et al. reply.

PMID- 10059624
TI  - Comment on "Invariant measure and turbulent pinch in tokamaks"

PMID- 10059625
TI  - Isichenko, Gruzinov, and Diamond reply.

PMID- 10059626
TI  - Comment on "Transverse gauge interactions and the vanquished Fermi liquid"

PMID- 10059627
TI  - Chakravarty, Norton, and Syljuasen reply.

PMID- 10059628
TI  - Comment on "13C NMR study of layered organic superconductors based on BEDT-TTF
      molecules"

PMID- 10059629
TI  - Kawamoto et al. reply.

PMID- 10059631
TI  - Exact solution to the mean exit time problem for free inertial processes driven
      by Gaussian white noise.

PMID- 10059632
TI  - Universal scaling functions in critical phenomena.

PMID- 10059633
TI  - Two-dimensional magnetotransport according to the classical Lorentz model.

PMID- 10059634
TI  - Cosmology with a TeV mass Higgs field breaking the grand-unified-theory gauge
      symmetry.

PMID- 10059635
TI  - Hidden symmetries of two-dimensional string effective action.

PMID- 10059636
TI  - Anomalous diffusion in chaotic scattering.

PMID- 10059637
TI  - Reducibility and thermal scaling of charge distributions in multifragmentation.

PMID- 10059638
TI  - Do hollow atoms exist in front of an insulating LiF(100) surface?

PMID- 10059639
TI  - Quantum shell effect on dissociation energies, shapes, and thermal properties of
      metallic clusters from the random matrix model.

PMID- 10059641
TI  - Kink arrays and solitary structures in an optically biased phase transition.

PMID- 10059640
TI  - Solitonlike propagation of exciton-polariton pulses supported by biexciton two
      photon dispersion.

PMID- 10059642
TI  - Stokes drag at the molecular level.

PMID- 10059644
TI  - Scaling relations for a randomly advected passive scalar field.

PMID- 10059643
TI  - Hydrodynamic convection in a two-dimensional Couette cell.

PMID- 10059645
TI  - Two-dimensional Navier-Stokes simulation of deformation and breakup of liquid
      patches.

PMID- 10059646
TI  - Large-amplitude ion acoustic waves in a laser-produced plasma.

PMID- 10059647
TI  - Absorption of ultrashort laser pulses by solid targets heated rapidly to
      temperatures 1-1000 eV.

PMID- 10059649
TI  - Fluctuating fluid interfaces.

PMID- 10059648
TI  - Transparent nondiffracting polarization rotation regime: A synchrotron x-ray
      study.

PMID- 10059650
TI  - Abnormal thickness and stability of nonequilibrium liquid films.

PMID- 10059651
TI  - Atomic scale studies of segregation at ceramic/metal heterophase interfaces.

PMID- 10059652
TI  - Branching of critical conditions for Si(111)-(7 x 7) oxidation.

PMID- 10059653
TI  - Interface depinning, self-organized criticality, and the Barkhausen effect.

PMID- 10059654
TI  - Anomalous fcc crystal structure of thorium metal.

PMID- 10059655
TI  - Quantitative transmission electron microscopy in substitutionally disordered
      alloys.

PMID- 10059656
TI  - Molecular geometry optimization with a genetic algorithm.

PMID- 10059657
TI  - Interplay of disorder and nonlinearity on carrier ground state.

PMID- 10059659
TI  - Kondo effect in a Luttinger liquid: Exact results from conformal field theory.

PMID- 10059658
TI  - Towards the identification of the dominant donor in GaN.

PMID- 10059660
TI  - Weak levitation of 2D delocalized states in a magnetic field.

PMID- 10059662
TI  - Deviations from Fermi-liquid behavior above Tc in 2D short coherence length
      superconductors.

PMID- 10059661
TI  - Nonequilibrium acoustic phonon-assisted tunneling in GaAs/(AlGa)As double barrier
      devices.

PMID- 10059663
TI  - Phonon and magnetic neutron scattering at 41 meV in YBa2Cu3O7.

PMID- 10059664
TI  - Topology of the order parameter in the Little-Parks experiment.

PMID- 10059665
TI  - Anisotropy of upper critical field and pairing symmetry.

PMID- 10059666
TI  - Magnetic anisotropy of 3d transition-metal clusters.

PMID- 10059667
TI  - Suppression of biquadratic coupling in Fe/Cr(001) superlattices below the Neel
      transition of Cr.

PMID- 10059668
TI  - Impulsive light scattering by coherent phonons in LaAlO3: Disorder and boundary
      effects.

PMID- 10059669
TI  - Ultrafast traveling spike autosolitons in reaction-diffusion systems.

PMID- 10059670
TI  - Survival probability of H2(v=1,J=1) scattered from Cu(110).

PMID- 10059671
TI  - Almost any quantum logic gate is universal.

PMID- 10059672
TI  - Comment on "Decoherence, chaos, and the second law"

PMID- 10059673
TI  - Zurek and Paz reply.

PMID- 10059674
TI  - Comment on "Thermodynamics of a one-dimensional ideal gas with fractional
      exclusion statistics"

PMID- 10059675
TI  - Murthy and Shankar reply.

PMID- 10059679
TI  - Neural network differential equation and plasma equilibrium solver.

PMID- 10059678
TI  - Statistical-mechanical foundation of the ubiquity of Levy distributions in
      Nature.

PMID- 10059680
TI  - Determination of the electron's atomic mass and the proton/electron mass ratio
      via Penning trap mass spectroscopy.

PMID- 10059682
TI  - Supersymmetric contributions to the quark-lepton universality violation in
      charged currents.

PMID- 10059681
TI  - Multiparticle dynamics in an expanding universe.

PMID- 10059684
TI  - E1+/M1+ and S1+/M1+ from an analysis of p(e,e'p) pi 0 in the region of the Delta
      (1232) resonance at Q2=3.2(GeV/c)2.

PMID- 10059683
TI  - Measurement of the left-right forward-backward asymmetry for charm quarks with
      D*+ and D+ mesons.

PMID- 10059685
TI  - Second generation leptoquark search in pp-bar collisions at sqrt s=1.8 TeV.

PMID- 10059687
TI  - Possible enhancement of magnetic dipole transitions between Gamow-Teller and
      isobaric analog states.

PMID- 10059686
TI  - Measurement of the average B hadron lifetime in Z0 decays using reconstructed
      vertices.

PMID- 10059689
TI  - Measurement of the 1s2s1S0-1s2p3P1 interval in heliumlike nitrogen.

PMID- 10059688
TI  - Centrality dependence of antiproton production in Au+Au collisions.

PMID- 10059690
TI  - Single atom quasi-Penning trap.

PMID- 10059692
TI  - Inducing coherent oscillations in the electron transfer dynamics of a strongly
      dissipative system with pulsed monochromatic light.

PMID- 10059691
TI  - Giant K doubling in the infrared spectrum of CH3OH: A sensitive probe for CH3
      rock/CO-stretch/OH-bend vibrational coupling.

PMID- 10059693
TI  - Charge transfer from the negative-energy continuum: Alternative mechanism for
      pair production in relativistic atomic collisions.

PMID- 10059694
TI  - Time-delayed second harmonic generation.

PMID- 10059695
TI  - Semiclassical description of tunneling in mixed systems: Case of the annular
      billiard.

PMID- 10059696
TI  - Attracting manifold for a viscous topology transition.

PMID- 10059697
TI  - Global diffusion in a realistic three-dimensional time-dependent nonturbulent
      fluid flow.

PMID- 10059698
TI  - Momentum and energy transfer in an ionospheric critical ionization velocity
      experiment.

PMID- 10059699
TI  - Three-dimensional single mode Rayleigh-Taylor experiments on nova.

PMID- 10059700
TI  - Second harmonic generation of stimulated raman scattered light in underdense
      plasmas.

PMID- 10059701
TI  - Enhanced transport during pellet injection in the Rijnhuizen tokamak RTP.

PMID- 10059702
TI  - Measurements of the production and transport of helium ash in the TFTR tokamak.

PMID- 10059703
TI  - Ordering of C60 on anisotropic surfaces.

PMID- 10059704
TI  - Synchronization in a lattice model of pulse-coupled oscillators.

PMID- 10059706
TI  - Heat capacity measurements of 3He-4He mixtures in aerogel.

PMID- 10059705
TI  - Glass transition singularities.

PMID- 10059707
TI  - Contact angle of liquid 4He on a Cs surface.

PMID- 10059709
TI  - Topological interaction of Coulombic impurity centers with dislocations in
      semiconductors.

PMID- 10059708
TI  - Novel edge magnetoplasmons in a two-dimensional sheet of 4He+ ions.

PMID- 10059710
TI  - Hydrogen-induced generation of acceptorlike defects in polycrystalline silicon.

PMID- 10059712
TI  - Observation of the "Dark exciton" in CdSe quantum dots.

PMID- 10059711
TI  - Random matrix model and the Calogero-Sutherland model: A novel current-density
      mapping.

PMID- 10059713
TI  - Coupling between planes and chains in YBa2Cu3O7: A possible solution for the
      order parameter controversy.

PMID- 10059714
TI  - Vortex dynamics and the Hall anomaly: A microscopic analysis.

PMID- 10059715
TI  - Resistance anomaly and excess voltage near superconducting interfaces.

PMID- 10059716
TI  - Neutron experiments on antiferromagnetic nuclear order in silver at Picokelvin
      temperatures.

PMID- 10059717
TI  - Determination of spin- and orbital-moment anisotropies in transition metals by
      angle-dependent x-ray magnetic circular dichroism.

PMID- 10059718
TI  - Microscopic origin of magnetic anisotropy in Au/Co/Au probed with x-ray magnetic
      circular dichroism.

PMID- 10059719
TI  - Experimental observation of magnetic surface polaritons in FeF2 by attenuated
      total reflection.

PMID- 10059720
TI  - Enhanced compressibility and pressure-induced structural changes of
      nanocrystalline iron: in situ Mossbauer spectroscopy.

PMID- 10059721
TI  - Raman scattering enhancement by optical confinement in a semiconductor planar
      microcavity.

PMID- 10059722
TI  - Points, walls, and loops in resonant oscillatory media.

PMID- 10059723
TI  - Bounds for predictive errors in the statistical mechanics of supervised learning.

PMID- 10059724
TI  - Comment on "Phase separation in two-dimensional fluid mixtures"

PMID- 10059725
TI  - Kinetics of cluster-cluster colloidal aggregation.

PMID- 10059726
TI  - Thorn and Seesselberg reply.

PMID- 10059731
TI  - Photon scattering from atoms in an atom interferometer: Coherence lost and
      regained.

PMID- 10059732
TI  - Decoherence, continuous observation, and quantum computing: A cavity QED model.

PMID- 10059734
TI  - Primordial magnetic fields from string cosmology.

PMID- 10059733
TI  - Observation of cosmic-ray antiprotons at energies below 500 MeV.

PMID- 10059735
TI  - Flavor changing neutral scalar currents at micro+ micro- colliders.

PMID- 10059736
TI  - Measurement of the D+s--> eta

PMID- 10059739
TI  - Multiple time scales in the microwave ionization of Rydberg atoms.

PMID- 10059737
TI  - Measurements of the decays tau --->h-h+h- nu tau and tau --->h-h+h- pi 0 nu tau.

PMID- 10059738
TI  - Transverse energy production in 208Pb+Pb collisions at 158 GeV per nucleon.

PMID- 10059740
TI  - Measuring coherence while observing noise.

PMID- 10059742
TI  - Coherent and incoherent drifting pulse dynamics in a complex Ginzburg-Landau
      equation.

PMID- 10059741
TI  - Observation of polarization of the soft x-ray laser line in neonlike germanium
      ions.

PMID- 10059743
TI  - Anomalous scaling of the passive scalar.

PMID- 10059744
TI  - Hexagons, kinks, and disorder in oscillated granular layers.

PMID- 10059745
TI  - Analysis of the thermal equilibrium state of bunched beams with a streak camera.

PMID- 10059746
TI  - An electron-positron beam-plasma experiment.

PMID- 10059747
TI  - Ion-controlled collisionless magnetic reconnection.

PMID- 10059748
TI  - Experimental evidence of interpenetration and high ion temperature in colliding
      plasmas.

PMID- 10059749
TI  - Evaluation of a foam buffer target design for spatially uniform ablation of laser
      irradiated plasmas.

PMID- 10059750
TI  - Generation of hot solid-density plasmas by laser radiation pressure confinement.

PMID- 10059751
TI  - Measurement of magnetic fluctuation induced energy transport in a tokamak.

PMID- 10059752
TI  - Structure and stability of molecular carbon: Importance of electron correlation.

PMID- 10059754
TI  - Rayleigh waves at vicinal surfaces.

PMID- 10059753
TI  - Are nanophase grain boundaries anomalous?

PMID- 10059755
TI  - Universal short-time behavior in critical dynamics near surfaces.

PMID- 10059756
TI  - Viscous bursting of suspended films.

PMID- 10059757
TI  - Energetics of Ni-induced vacancy line defects on Si(001).

PMID- 10059758
TI  - Anisotropic Kuramoto-Sivashinsky equation for surface growth and erosion.

PMID- 10059759
TI  - Shape of the tip and the formation of sidebranches of xenon dendrites.

PMID- 10059760
TI  - Magnetopolarizability at the metal-insulator transition.

PMID- 10059761
TI  - Controlled Exciton-Photon Interaction in Semiconductor Bulk Microcavities.

PMID- 10059763
TI  - ac-Field-controlled Anderson localization in disordered semiconductor
      superlattices.

PMID- 10059764
TI  - Electronic structure of monolayer hexagonal boron nitride physisorbed on metal
      surfaces.

PMID- 10059762
TI  - Electron localization in mixed-valence manganites.

PMID- 10059765
TI  - Statistical distributions of level widths and conductance peaks in irregularly
      shaped quantum dots.

PMID- 10059766
TI  - Fractional quantum Hall effect around nu =3/2: Composite fermions with a spin.

PMID- 10059767
TI  - Phases of Josephson junction ladders.

PMID- 10059768
TI  - Microwave Fabry-Perot transmission through YBaCuO superconducting thin films.

PMID- 10059769
TI  - Impurity scattering and triplet superconductivity in UPt3.

PMID- 10059770
TI  - Vortex lock-in deep in the Bose glass.

PMID- 10059771
TI  - Spin-echo double resonance NMR evidence for preferential like-cation clustering
      in mixed-alkali disilicate glasses.

PMID- 10059772
TI  - Band structure effects in ejection of Ni atoms in fine structure states.

PMID- 10059773
TI  - Kinetics of simple reactions in a dichotomic barrier model.

PMID- 10059774
TI  - Pseudocritical behavior and unbinding of phospholipid bilayers.

PMID- 10059775
TI  - Comment on "Direct determination of the electron-electron-hole Auger threshold
      energy in silicon"

PMID- 10059777
TI  - Comment on "Crossover between dissipative and nondissipative electron transport
      in metal wires"

PMID- 10059776
TI  - Chen et al. reply.

PMID- 10059778
TI  - Wybourne and Kanskar reply.

PMID- 10059779
TI  - Comment on "Formation of crystalline AgxNi1-x solid solutions of unusually high
      supersaturation by laser ablation deposition"

PMID- 10059780
TI  - van Ingen, Fastenau, and Mittemeijer reply.

PMID- 10059783
TI  - Gravitational waves generated by the vacuum stress.

PMID- 10059782
TI  - Bose-Einstein condensation in a gas of sodium atoms.

PMID- 10059784
TI  - Big Bang nucleosynthesis in crisis?

PMID- 10059785
TI  - Assessing Big-Bang nucleosynthesis.

PMID- 10059786
TI  - Geometric model of the generations.

PMID- 10059787
TI  - Upper bound on the WR mass in automatically R-conserving supersymmetric models.

PMID- 10059788
TI  - Limits on nu micro( nu micro)--> nu tau ( nu tau ) and nu micro( nu micro)-->( nu
      e) nu e oscillations from a precision measurement of neutrino-nucleon neutral
      current interactions.

PMID- 10059790
TI  - Hydrodynamics near the QCD phase transition: Looking for the longest-lived
      fireball.

PMID- 10059791
TI  - Enhancement of low-mass dileptons in heavy ion collisions.

PMID- 10059789
TI  - Study of tp-bar collisions using total transverse energy.

PMID- 10059792
TI  - Resolved-sideband Raman cooling of a bound atom to the 3D zero-point energy.

PMID- 10059793
TI  - Nonspreading electronic wave packets and conductance fluctuations.

PMID- 10059794
TI  - Sub-poissonian photon statistics in a three-wave interaction starting in the out
      of-phase regime.

PMID- 10059795
TI  - Controlling complexity.

PMID- 10059797
TI  - Lattice Boltzmann study of hydrodynamic spinodal decomposition.

PMID- 10059796
TI  - Spatiotemporal dynamics of lasers with a large fresnel number.

PMID- 10059798
TI  - Coexisting pulses in a model for binary-mixture convection.

PMID- 10059799
TI  - Observation of plasma satellite lines in laser produced plasmas.

PMID- 10059800
TI  - Surface tension of liquid metals: Results from measurements on ground and in
      space.

PMID- 10059801
TI  - Periodic in-layer director modulations responsible for the stripe texture
      formation in chiral smectic-C phase.

PMID- 10059802
TI  - Generic rigidity percolation: The pebble game.

PMID- 10059803
TI  - Stressed backbone and elasticity of random central-force systems.

PMID- 10059804
TI  - Effect of container size on gelation time: Experiments and simulations.

PMID- 10059806
TI  - Effect of the interface on the properties of composite media.

PMID- 10059805
TI  - Direct imaging of spatially varying potential and charge across internal
      interfaces in solids.

PMID- 10059807
TI  - Self-organized branching processes: Mean-field theory for avalanches.

PMID- 10059809
TI  - Dynamics of the formation of an electron bubble in liquid helium.

PMID- 10059808
TI  - Percolation-enhanced localization in the disordered bosonic Hubbard model.

PMID- 10059810
TI  - Thermal evolution of spin-polarons.

PMID- 10059811
TI  - Continuous wetting transitions in Xe adsorbed on NaF and on plated Cs and Rb
      substrates.

PMID- 10059812
TI  - Optical dispersion by Wannier excitons.

PMID- 10059813
TI  - Hall resistance in the Hopping regime: A "Hall insulator"?

PMID- 10059814
TI  - Photon-assisted electric field domains and multiphoton-assisted tunneling in
      semiconductor superlattices.

PMID- 10059816
TI  - Temperature dependent scattering of composite fermions.

PMID- 10059815
TI  - Dynamic localization, absolute negative conductance, and stimulated, multiphoton
      emission in sequential resonant tunneling semiconductor superlattices.

PMID- 10059817
TI  - Ensemble density functional theory of the fractional quantum Hall effect.

PMID- 10059818
TI  - Thermoelectric power: A simple, instructive probe of high-Tc superconductors.

PMID- 10059819
TI  - Electric-field-induced electronic instability in amorphous Mo3Si superconducting
      films.

PMID- 10059820
TI  - Superconducting state of kappa -(ET)2CUBr studied by 13C NMR: Evidence for vortex
      core-induced nuclear relaxation and unconventional pairing.

PMID- 10059821
TI  - Theory of the resonant neutron scattering of high-Tc superconductors.

PMID- 10059822
TI  - Theory of neutron scattering in the normal and superconducting states of
      YBa2Cu3O6+x.

PMID- 10059823
TI  - Neutron scattering and superconducting order parameter in YBa2Cu3O7.

PMID- 10059824
TI  - Aging in a magnetic particle system.

PMID- 10059825
TI  - Macroscopic quantum coherence and quasidegeneracy in antiferromagnets.

PMID- 10059826
TI  - Self-diffusion of an entangled DNA molecule by reptation.

PMID- 10059827
TI  - Comment on "Nonlocal symmetry for QED" and "Relativistically covariant symmetry
      in QED"

PMID- 10059828
TI  - Lavelle and McMullan reply.

PMID- 10059829
TI  - Tang and Finkelstein reply.

PMID- 10059830
TI  - Surface relaxation below the roughening temperature.

PMID- 10059834
TI  - Mean Switching Frequency Locking in Stochastic Bistable Systems Driven by a
      Periodic Force.

PMID- 10059835
TI  - Instabilities in Close Neutron Star Binaries.

PMID- 10059836
TI  - All the Four-Dimensional Static, Spherically Symmetric Solutions of Abelian
      Kaluza-Klein Theory.

PMID- 10059837
TI  - Equation of State for the SU(3) Gauge Theory.

PMID- 10059839
TI  - Relation between the Scissors Mode and the Interacting Boson Model Deformation.

PMID- 10059838
TI  - First Measurement of the T-Odd Correlation between the Z0 Spin and the Three-Jet
      Plane Orientation in Polarized Z0 Decays into Three Jets.

PMID- 10059840
TI  - Half-Life Measurements of Bare, Mass-Resolved Isomers in a Storage-Cooler Ring.

PMID- 10059841
TI  - Scaling Laws, Shell Effects, and Transient Times in Fission Probabilities.

PMID- 10059842
TI  - Measurement of Compound Nucleus Space-Time Extent with Two-Neutron Correlation
      Functions.

PMID- 10059843
TI  - Three-Dimensional Laser Cooling of Helium Beyond the Single-Photon Recoil Limit.

PMID- 10059844
TI  - Long-Range Order in Laser-Cooled, Atomic-Ion Wigner Crystals Observed by Bragg
      Scattering.

PMID- 10059845
TI  - Nature of Quantum Localization in Atomic Momentum Transfer Experiments.

PMID- 10059846
TI  - Robust Acoustic Time Reversal with High-Order Multiple Scattering.

PMID- 10059847
TI  - Coherent Radiation Reaction in Free-Electron Sources.

PMID- 10059848
TI  - Plasma-Dust Crystals and Brownian Motion.

PMID- 10059849
TI  - Unified Theory of Stimulated Raman Scattering and Two-Plasmon Decay in
      Inhomogeneous Plasmas: High Frequency Hybrid Instability.

PMID- 10059850
TI  - Nonlinear Self-Sustained Drift-Wave Turbulence.

PMID- 10059852
TI  - Orientational Ordering of Solid C70.

PMID- 10059851
TI  - Role of Hydrogen in C and Si (001) Homoepitaxy.

PMID- 10059853
TI  - Forced Brillouin Spectroscopy Using Frequency-Tunable Continuous Wave Lasers.

PMID- 10059854
TI  - Quasiparticle Excitations, Bose Condensation, and the f-Sum Rule.

PMID- 10059855
TI  - Near-Surface Buckling in Strained Metal Overlayer Systems.

PMID- 10059857
TI  - Transition to Multilayer Kinetic Roughening for Metal (100) Homoepitaxy.

PMID- 10059856
TI  - Coarsening of Unstable Surface Features during Fe(001) Homoepitaxy.

PMID- 10059858
TI  - Observation of a Distributed Epitaxial Oxide in Thermally Grown SiO2 on Si(001).

PMID- 10059859
TI  - Direct Observation of Compositionally Homogeneous a-C:H Band-Gap-Modulated
      Superlattices.

PMID- 10059860
TI  - Tunneling Evidence for the Quasiparticle Gap in Kondo Semiconductors CeNiSn and
      CeRhSb.

PMID- 10059861
TI  - Direct Observation of the Coulomb Correlation Gap in a Nonmetallic Semiconductor,
      Si:B.

PMID- 10059862
TI  - Temporal Order in Dirty Driven Periodic Media.

PMID- 10059863
TI  - Finite-Temperature Fermi-Edge Singularity in Tunneling Studied Using Random
      Telegraph Signals.

PMID- 10059864
TI  - Coulomb Interaction and Disorder at q=2kF: A Novel Instability of the Fermi Sea
      and Implications for Amorphous Alloys.

PMID- 10059865
TI  - Scaling of the Coulomb Energy Due to Quantum Fluctuations in the Charge on a
      Quantum Dot.

PMID- 10059866
TI  - Giant Peaks of the Conductance in Polycrystalline Bi Nanobridges.

PMID- 10059867
TI  - Evidence for Skyrmions and Single Spin Flips in the Integer Quantized Hall
      Effect.

PMID- 10059868
TI  - Edge and Bulk of the Fractional Quantum Hall Liquids.

PMID- 10059869
TI  - Exact Ground States of Generalized Hubbard Models.

PMID- 10059870
TI  - Random Quantum Spin Chains: A Real-Space Renormalization Group Study.

PMID- 10059871
TI  - Oscillatory Interlayer Exchange Coupling with the Cu Cap Layer Thickness in
      Co/Cu/Co/Cu(100).

PMID- 10059872
TI  - Quantum Dynamical Echoes in the Spin Diffusion in Mesoscopic Systems.

PMID- 10059873
TI  - Three-Dimensional Apollonian Packing as a Model for Dense Granular Systems.

PMID- 10059874
TI  - Differential Flow Induced Chemical Instability on a Rotating Disk.

PMID- 10059875
TI  - Demonstration of Marginal Stability Theory by a 200-kW Second-Harmonic Gyro-TWT
      Amplifier.

PMID- 10059877
TI  - Comment on "Preroughening and Reentrant Layering Transitions on Triangular
      Lattice Substrates"

PMID- 10059876
TI  - Long-Range Order in a Two-Dimensional Dynamical XY Model: How Birds Fly Together.

PMID- 10059878
TI  - Weichman and Goodstein Reply.

PMID- 10059879
TI  - Comment on "Optical Response of Arrays of Spheres from the Theory of Hypercomplex
      Variables"

PMID- 10059880
TI  - Vagov, Radchik, and Smith Reply.

PMID- 10059884
TI  - New high-intensity source of polarization-entangled photon pairs.

PMID- 10059885
TI  - Power series expansion for the time evolution operator with a harmonic-oscillator
      reference system.

PMID- 10059886
TI  - Semiclassical trace formulas of near-integrable systems: Resonances.

PMID- 10059887
TI  - Reconciling sterile neutrinos with Big Bang nucleosynthesis.

PMID- 10059888
TI  - String radiative backreaction.

PMID- 10059891
TI  - Elastic electron scattering from the deuteron using the gross equation.

PMID- 10059889
TI  - Upsilon production in pp-bar collisions at sqrt s=1.8 TeV.

PMID- 10059890
TI  - Observation of a narrow state decaying into Xi +c pi -

PMID- 10059893
TI  - Nuclear spin-rotation interaction in the hydrogen molecular ion.

PMID- 10059892
TI  - Multifragmentation in E/A=35m MeV collisions: Evidence for a Coulomb driven
      breakup?

PMID- 10059894
TI  - Observation of enhanced electron-ion recombination rates at very low energies.

PMID- 10059895
TI  - Elimination of optical self-focusing by population trapping.

PMID- 10059897
TI  - Quasiperiodic motion in the billiard problem with a softened boundary.

PMID- 10059896
TI  - Spectral statistics: From disordered to chaotic systems.

PMID- 10059898
TI  - Long-wavelength instability in surface-tension-driven Benard convection.

PMID- 10059899
TI  - Radial electric fields during L-to-H transition and edge-localized modes from
      charge-exchange diagnostics of Ripple-trapped particles.

PMID- 10059900
TI  - Nonlocal electron transport in a plasma.

PMID- 10059901
TI  - Dipole moments on dust particles immersed in anisotropic plasmas.

PMID- 10059902
TI  - Effect of filamentation of Brillouin scattering in large underdense plasmas
      irradiated by incoherent laser light.

PMID- 10059903
TI  - Improved confinement with reversed magnetic shear in TFTR.

PMID- 10059904
TI  - Enhanced confinement and stability in DIII-D discharges with reversed magnetic
      shear.

PMID- 10059905
TI  - Elasticity of semiflexible biopolymer networks.

PMID- 10059906
TI  - Isotropic Lifshitz behavior in block copolymer-homopolymer blends.

PMID- 10059907
TI  - Direct imaging of the percolation network in a three-dimensional disordered
      conductor-insulator composite.

PMID- 10059908
TI  - Internal friction of subnanometer a-SiO2 films.

PMID- 10059909
TI  - Anomalous spin diffusion in a two-dimensional percolating ising antiferromagnet.

PMID- 10059910
TI  - Nature of dislocations in silicon.

PMID- 10059911
TI  - Elastic effects on phase segregation in alloys with external stresses.

PMID- 10059912
TI  - Hydrogen in GaN: Novel aspects of a common impurity.

PMID- 10059914
TI  - Bulk versus surface transport of nickel and cobalt on silicon.

PMID- 10059913
TI  - Faceting through the propagation of nucleation.

PMID- 10059915
TI  - Stochastic model for surface erosion via ion sputtering: Dynamical evolution from
      ripple morphology to rough morphology.

PMID- 10059916
TI  - Preroughening, diffusion, and growth of a fcc(111) surface.

PMID- 10059917
TI  - Electrochemical deposition of copper on a gold electrode in sulfuric acid:
      resolution of the interfacial structure.

PMID- 10059919
TI  - Electron-ion correlation in liquid metals from first principles: Liquid Mg and
      liquid Bi.

PMID- 10059918
TI  - Oscillatory surface in-plane lattice spacing during growth of Co and of Cu on a
      Cu(001) single crystal.

PMID- 10059920
TI  - Identification of Se2 and Se-As pairs in silicon by elemental transmutation.

PMID- 10059921
TI  - Simultaneous structural, magnetic, and electronic transitions in La1-xCaxMnO3
      with x=0.25 and 0.50.

PMID- 10059922
TI  - Exact perturbative solution of the Kondo problem.

PMID- 10059923
TI  - Three-dimensional disordered conductors in a strong magnetic field: Surface
      states and quantum Hall plateaus.

PMID- 10059924
TI  - Evidence for Gamma -X transport in type-I GaAs/AlAs semiconductor superlattices.

PMID- 10059925
TI  - Isotope effect in d-wave superconductors.

PMID- 10059926
TI  - Theory for the excitation spectrum of high-Tc superconductors: quasiparticle
      dispersion and shadows of the Fermi surface.

PMID- 10059927
TI  - Collective Josephson plasma resonance in the vortex state of Bi2Sr2CaCu2O8+
      delta.

PMID- 10059928
TI  - In-plane and c-circumflex-axis microwave penetration depth of Bi2Sr2Ca1Cu2O8+
      delta crystals.

PMID- 10059929
TI  - First-order decoupling transition in the vortex lattice of Bi2Sr2CaCu2O8 from
      local mutual inductance measurements.

PMID- 10059930
TI  - Meron-cluster simulation of the theta vacuum in the 2D O(3) model.

PMID- 10059931
TI  - Avalanches, Barkhausen noise, and plain old criticality.

PMID- 10059932
TI  - Spatially-distributed pulsed gradient spin echo NMR using single-wire proximity.

PMID- 10059933
TI  - Dynamics and transport of electronic carriers in thin gold films.

PMID- 10059934
TI  - Electronic band dispersion and pseudogap in quasicrystals: Angular-resolved
      photoemission studies on icosahedral Al70Pd21.5Mn8.5.

PMID- 10059935
TI  - Electrophoretic mobility of asymmetric reptating polymers.

PMID- 10059936
TI  - Depletion stabilization by semidilute rods.

PMID- 10059937
TI  - Transport at a van Hove singularity in cuprate superconductors.

PMID- 10059938
TI  - Newns et al. reply.

PMID- 10059939
TI  - Evidence for complex subleading exponents from the high-temperature expansion of
      Dyson's hierarchical ising model.

PMID- 10059940
TI  - Symmetry nonrestoration at high temperature and the monopole problem.

PMID- 10059942
TI  - Kaon energies in dense matter.

PMID- 10059941
TI  - Numerical evidence for the observation of a scalar glueball.

PMID- 10059943
TI  - Intruder states and the onset of deformation in the neutron-deficient even-even
      polonium isotopes.

PMID- 10059944
TI  - Raman cooling of cesium below 3 nK: New approach inspired by Levy flight
      statistics.

PMID- 10059945
TI  - Far-infrared multiphoton ionization of lithium Rydberg atoms bypassing a Cooper
      minimum.

PMID- 10059947
TI  - Adaptive phase measurements of optical modes: Going beyond the marginal Q
      distribution.

PMID- 10059946
TI  - Bragg diffraction in an atomic lattice bound by light.

PMID- 10059949
TI  - Chaotic masking scheme with a linear inverse system.

PMID- 10059948
TI  - Magnetic control of optical spatial solitons.

PMID- 10059950
TI  - Atom optics realization of the quantum delta -kicked rotor.

PMID- 10059951
TI  - Universal classical mechanism of free-electron lasing without inversion.

PMID- 10059953
TI  - Azimuthally propagating ring vortices in a model for nonaxisymmetric Taylor
      vortex flow.

PMID- 10059952
TI  - Squeezing and intermode correlations in laser diodes.

PMID- 10059954
TI  - Viscous flow at infinite Marangoni number.

PMID- 10059955
TI  - Memory-induced low frequency oscillations in closed convection boxes.

PMID- 10059956
TI  - Relativistic ponderomotive force, Uphill acceleration, and transition to chaos.

PMID- 10059957
TI  - Dynamics of runaway electrons in the magnetic field of a tokamak.

PMID- 10059958
TI  - Flux quantization in magnetic nanowires imaged by electron holography.

PMID- 10059959
TI  - Violation of adiabatic scaling in the distribution of particles nucleated in a
      rapid quench.

PMID- 10059960
TI  - Glass formation in a lattice model for living polymers.

PMID- 10059961
TI  - Core structure of a vortex in superfluid 4He.

PMID- 10059962
TI  - Low energy ion scattering investigation of the order-disorder transition in the
      first atomic layer of the Cu3Au(100) surface.

PMID- 10059963
TI  - Singular quasiparticle scattering in the proximity of charge instabilities.

PMID- 10059964
TI  - Direct evidence of the role of hybridization in the x-ray magnetic circular
      dichroism of alpha -Ce.

PMID- 10059965
TI  - New phases in an extended Hubbard model explicitly including atomic
      polarizabilities.

PMID- 10059966
TI  - Logarithmic divergence of both in-plane and out-of-plane normal-state
      resistivities of superconducting La2-xSrxCuO4 in the zero-temperature limit.

PMID- 10059967
TI  - Bose and vortex glasses in high temperature superconductors.

PMID- 10059968
TI  - Resistive hysteresis and nonlinear I-V characteristics at the first-order melting
      of the Abrikosov vortex lattice.

PMID- 10059969
TI  - Length-scale-dependent layer decoupling in layered systems.

PMID- 10059971
TI  - Investigation of spin chirality by polarized neutrons.

PMID- 10059970
TI  - Ferromagnetism in Hubbard models.

PMID- 10059972
TI  - Phase shifts in the oscillatory interlayer exchange coupling across Cu layers.

PMID- 10059973
TI  - Non-Fermi-liquid behavior in transport in (TMTSF)2PF6.

PMID- 10059975
TI  - Dynamic exchange effects in broadband dielectric spectroscopy.

PMID- 10059974
TI  - Reproducibility of magnetic avalanches in an Fe-Ni-Co ferromagnet.

PMID- 10059976
TI  - Electron dynamics in copper metallic nanoparticles probed with femtosecond
      optical pulses.

PMID- 10059977
TI  - Accelerated expansion of laser-ablated materials near a solid surface.

PMID- 10059978
TI  - Measurement of conditional phase shifts for quantum logic.

PMID- 10059979
TI  - Demonstration of a fundamental quantum logic gate.

PMID- 10059980
TI  - Thermodynamic analysis of inhomogeneous random walks: Localization and phase
      transitions.

PMID- 10059981
TI  - Dirichlet Branes and Ramond-Ramond charges.

PMID- 10059982
TI  - New value of the alpha 3 electron anomalous magnetic moment.

PMID- 10059984
TI  - Nondipolar asymmetries of photoelectron angular distributions.

PMID- 10059983
TI  - Heated nuclear matter, condensation phenomena, and the hadronic equation of
      state.

PMID- 10059985
TI  - Novel structure in the H alpha -line profile of hydrogen in a dense helium
      plasma.

PMID- 10059986
TI  - Near atomic scale studies of electronic structure at grain boundaries in Ni3Al.

PMID- 10059988
TI  - A new phase of tethered membranes: Tubules.

PMID- 10059987
TI  - First principles simulations of silicon nanoindentation.

PMID- 10059990
TI  - Crystal surfaces with correlated disorder: Phase transitions between roughening
      and super-roughening.

PMID- 10059989
TI  - Binding sites, migration paths, and barriers for hydrogen on Si(111)-(7 x 7).

PMID- 10059991
TI  - Temperature-induced smearing of the Coulomb gap: Experiment and computer
      simulation.

PMID- 10059992
TI  - Phase diagram for splay glass superconductivity.

PMID- 10059993
TI  - Single molecule emission characteristics in near-field microscopy.

PMID- 10059994
TI  - State-resolved characterization of a surface reaction: Evidence for concerted
      dynamics.

PMID- 10059995
TI  - Foam mechanics at the bubble scale.

PMID- 10059996
TI  - Comment on "Determining the phase of a strong scattering amplitude from its
      momentum dependence to better than 1 degrees "

PMID- 10059997
TI  - Briere and Winstein reply.

PMID- 10059999
TI  - Van den Broeck, Parrondo, and Toral reply.

PMID- 10059998
TI  - Comment on "Noise-induced nonequilibrium phase transition"

PMID- 10060001
TI  - Breathing solitary waves in a Sine-Gordon two-dimensional lattice.

PMID- 10060002
TI  - Phase space entropy and global phase space structures of (chaotic) quantum
      systems.

PMID- 10060003
TI  - Thermodynamics of anomalous diffusion.

PMID- 10060004
TI  - Quantum breaking of elastic string.

PMID- 10060005
TI  - Cooperative transport of Brownian particles.

PMID- 10060006
TI  - Kosterlitz-Thouless phase transition in the two dimensional linear sigma model.

PMID- 10060008
TI  - Cosmological gamma-ray bursts and the highest energy cosmic rays.

PMID- 10060007
TI  - Vanishing Hawking radiation from a uniformly accelerated black hole.

PMID- 10060010
TI  - Low Hubble constant from the physics of type Ia supernovae.

PMID- 10060009
TI  - Cosmic ray positrons at high energies: A new measurement.

PMID- 10060011
TI  - Supersymmetry breaking in the early universe.

PMID- 10060012
TI  - Determining the phase of a strong scattering amplitude from its momentum
      dependence to better than 1 degrees : The example of kaon regeneration.

PMID- 10060014
TI  - Renormalized proton-neutron quasiparticle random-phase approximation and its
      application to double beta decay.

PMID- 10060013
TI  - Rotation of an eight-quasiparticle isomer.

PMID- 10060015
TI  - Electron affinity of strontium.

PMID- 10060016
TI  - Creating metastable Schrodinger cat states.

PMID- 10060017
TI  - Transverse diffusion of light in Faraday-active media.

PMID- 10060018
TI  - Phase instabilities in the laser vector complex Ginzburg-Landau equation.

PMID- 10060019
TI  - Transversely pumped counterpropagating optical parametric oscillation and
      amplification.

PMID- 10060020
TI  - Scaling properties of circulation in moderate-Reynolds-number turbulent wakes.

PMID- 10060021
TI  - Measured local-velocity fluctuations in turbulent convection.

PMID- 10060022
TI  - Renormalized dissipation in plasmas with finite collisionality.

PMID- 10060024
TI  - X-Ray photon correlation spectroscopy study of Brownian motion of gold colloids
      in glycerol.

PMID- 10060023
TI  - Measurement of velocity distributions and recombination kinetics in tunnel
      ionized helium plasmas.

PMID- 10060025
TI  - Corrugational instabilities of thin copolymer films.

PMID- 10060026
TI  - Spontaneous chiral segregation in bidimensional films.

PMID- 10060027
TI  - Adsorption of colloidal particles in the presence of external fields.

PMID- 10060028
TI  - Renormalization group approach to the critical behavior of the forest-fire model.

PMID- 10060029
TI  - Many-body nature of the Meyer-Neldel compensation law for diffusion.

PMID- 10060030
TI  - Helium atoms in zeolite cages: Novel Mott-Hubbard and Bose-Hubbard systems.

PMID- 10060031
TI  - Experimental evidence of the wetting-nonwetting crossover for coherent quantum
      precession in superfluid 3He-B.

PMID- 10060032
TI  - Reconstruction and deconstruction of an sp metal surface.

PMID- 10060033
TI  - Role of surface states for the epitaxial growth on metal surfaces.

PMID- 10060034
TI  - Atomic-scale determination of misfit dislocation loops at metal-metal interfaces.

PMID- 10060036
TI  - Nonlinear screening and metallic islands created by defects of density waves in
      quasi-one-dimensional conductors.

PMID- 10060035
TI  - Photoemission spectra and structures of Si clusters at finite temperature.

PMID- 10060037
TI  - Dissipative dynamics of a two-state system, the Kondo problem, and the inverse
      square ising model.

PMID- 10060039
TI  - Magnetic nanostructures:4d clusters on Ag(001).

PMID- 10060038
TI  - Enhanced spin interactions in digital magnetic heterostructures.

PMID- 10060040
TI  - Tunneling potential barrier dependence of electron spin polarization.

PMID- 10060041
TI  - Spectral weight function for the half-filled Hubbard model: A singular value
      decomposition approach.

PMID- 10060042
TI  - Longitudinal superconductivity in vortex-line phases: A Monte Carlo study.

PMID- 10060043
TI  - Frequency and field variation of vortex dynamics in YBa2Cu3O7- delta.

PMID- 10060045
TI  - Critical fluctuations and disorder at the vortex liquid to crystal transition in
      type-II superconductors.

PMID- 10060044
TI  - Observation of paramagnetic Meissner effect in niobium disks.

PMID- 10060046
TI  - Tunneling in mesoscopic magnetic molecules.

PMID- 10060047
TI  - Silent satellites: Critical fluctuations in chromiun.

PMID- 10060048
TI  - Evidence for magnetic interactions between distant cations in yittrium iron
      garnet.

PMID- 10060049
TI  - Nuclear scattering of synchrotron radiation by 181TA.

PMID- 10060050
TI  - Magnetic raman scattering in two-dimensional spin-1/2 Heisenberg
      antiferromagnets: Spectral shape anomaly and magnetostrictive effects.

PMID- 10060051
TI  - Atomic structure of acceptors in Cd0.22Hg0.78Te: Discrimination between vacancies
      and ions based on positron lifetime and Hall data.

PMID- 10060052
TI  - Parity-broken dendrites.

PMID- 10060053
TI  - Fluctuations and stability of fisher waves.

PMID- 10060054
TI  - Complex electrical conductivity of water-in-oil microemulsions.

PMID- 10060055
TI  - Magnetic resonance images of coarsening inside a foam.

PMID- 10060057
TI  - Comment on "Exponential sensitivity and chaos in quantum systems"

PMID- 10060056
TI  - Continuum model for river networks.

PMID- 10060059
TI  - Comment on "Polaron origin for anharmonicity of the axial oxygen in YBa2Cu3O7"

PMID- 10060058
TI  - Blumel replies.

PMID- 10060060
TI  - Mustre de Leon et al. reply.

PMID- 10060061
TI  - Comment on "Pair and triple correlations in the A+B-->B diffusion-controlled
      reaction"

PMID- 10060062
TI  - Comment on "Pair and triple correlations in the A+B-->B diffusion-controlled
      reaction"

PMID- 10060063
TI  - Kuzovkov and Kotomin reply.

PMID- 10060065
TI  - Gleiser replies.

PMID- 10060064
TI  - Comment on "Dynamics of weak first order phase transitions"

PMID- 10060066
TI  - Instability of solitons governed by quadratic nonlinearities.

PMID- 10060067
TI  - Incorporation of quantum statistical features in molecular dynamics.

PMID- 10060068
TI  - New formalism for numerical relativity.

PMID- 10060069
TI  - Analysis of small- and medium-scale cosmic microwave background measurements.

PMID- 10060070
TI  - Properties of high-mass multijet events at the Fermilab proton-antiproton
      collider.

PMID- 10060071
TI  - Search for squarks and gluinos via radiative decays of neutralinos in proton
      antiproton collisions at sqrt s=1.8TeV.

PMID- 10060072
TI  - Search for squarks and gluinos in pp-bar collisions at sqrt s=1.8TeV.

PMID- 10060074
TI  - Realization of a magnetic mirror for cold atoms.

PMID- 10060073
TI  - Form factor ratio measurement in Lambda +c--> Lambda e+ nu e.

PMID- 10060075
TI  - Observation of continuum-continuum Autler-Townes splitting.

PMID- 10060076
TI  - Complexity of the minimum energy configurations.

PMID- 10060077
TI  - In-Beam polarization of light radioactive nuclei using grazing surface
      scattering.

PMID- 10060078
TI  - Direct measurement of the damping of toroidicity-induced Alfven eigenmodes.

PMID- 10060079
TI  - Confined alpha distribution measurements in a deuterium-tritium tokamak plasma.

PMID- 10060080
TI  - Diffusion in model disordered media.

PMID- 10060081
TI  - Mechanisms of chain diffusion in lamellar block copolymers.

PMID- 10060083
TI  - Structure of GaAs(100)-c(8 x 2)-Ga.

PMID- 10060082
TI  - Homogeneous equal-spin pairing superfluid state of 3He in aerogel.

PMID- 10060084
TI  - Electron Standing Wave at a Surface during Reflection High Energy Electron
      Diffraction and Adatom Height Determination.

PMID- 10060086
TI  - Interlayer mass transport in homoepitaxial and heteroepitaxial metal growth.

PMID- 10060085
TI  - Femtosecond desorption dynamics probed by time-resolved velocity measurements.

PMID- 10060087
TI  - New short-range ordered structure in Ni-Ge alloy.

PMID- 10060088
TI  - Common electronic structure and pentagon pairing in extractable fullerenes.

PMID- 10060089
TI  - Static response and local field factor of the electron gas.

PMID- 10060090
TI  - Resonant exchange scattering in dipole-forbidden d-d excitations in NiO(100).

PMID- 10060091
TI  - Viscosity of quantum Hall fluids.

PMID- 10060092
TI  - Localized excitons and breaking of chemical bonds at III-V (110) surfaces.

PMID- 10060093
TI  - Single-electron charging in double and triple quantum dots with tunable coupling.

PMID- 10060094
TI  - Coulomb blockade oscillations of conductance in the regime of strong tunneling.

PMID- 10060095
TI  - Possible glassiness in a periodic long-range Josephson array.

PMID- 10060096
TI  - Transformer configuration in three dimensional Josephson lattices at zero
      magnetic field.

PMID- 10060097
TI  - Influence of controlled quantum-mechanical charge and phase fluctuations on
      Josephson tunneling.

PMID- 10060099
TI  - Ab initio spin dynamics in magnets.

PMID- 10060098
TI  - Non-Fermi-liquid scaling of the magnetic response in UCu5-xPdx(x=1,1.5).

PMID- 10060100
TI  - Temperature variation of the interfilm exchange in magnetic multilayers: the
      influence of spin wave interactions.

PMID- 10060101
TI  - Evidence for the existence of long-range magnetic ordering in a liquid
      undercooled metal.

PMID- 10060103
TI  - Nuclear quadrupole resonance spectrum of La2CuO4.

PMID- 10060102
TI  - Soft x-ray resonant magnetic scattering from a magnetically coupled Ag/Ni
      multilayer.

PMID- 10060104
TI  - Simple realization of the Fredkin gate using a series of two-body operators.

PMID- 10060105
TI  - Exact first-passage exponents of 1D domain growth: Relation to a reaction
      diffusion model.

PMID- 10060106
TI  - Electro-osmosis on inhomogeneously charged surfaces.

PMID- 10060108
TI  - Neutron diffraction from shear ordered colloidal dispersions.

PMID- 10060107
TI  - Tracer diffusion in a Brownian fluid permeating a porous medium.

PMID- 10060109
TI  - Nuclear multifragmentation critical exponents.

PMID- 10060110
TI  - Gilkes et al. reply for the EOS Collaboration.

PMID- 10060111
TI  - Comment on "2-channel Kondo scaling in conductance signals from 2-level tunneling
      systems"

PMID- 10060112
TI  - Ralph et al. reply.

PMID- 10060113
TI  - Specific heat analysis of the spin-Peierls transition in CuGeO3.

PMID- 10060115
TI  - Lower bound for mutual information of a quantum channel.

PMID- 10060116
TI  - Bubble wall velocity in a first order electroweak phase transition.

PMID- 10060117
TI  - Quark mass textures within a finite non-Abelian dicyclic group.

PMID- 10060119
TI  - Hadronic light-by-light scattering effect on muon g-2.

PMID- 10060120
TI  - Measurements of the antineutrino spin asymmetry in beta decay of the neutron and
      restrictions on the mass of a right-handed gauge boson.

PMID- 10060121
TI  - Dilepton decay of giant resonances built on excited states of 28Si.

PMID- 10060118
TI  - Search for B-->

PMID- 10060122
TI  - Laser-stimulated recombination spectroscopy for the study of long-range
      interactions in highly charged Rydberg ions.

PMID- 10060123
TI  - Extremely cold positrons accumulated electronically in ultrahigh vacuum.

PMID- 10060124
TI  - Studies of electron-molecule scattering at microelectronvolt energies using very
      high-n Rydberg atoms.

PMID- 10060125
TI  - Measurement of branching ratios for the dissociative recombination of cold HD+
      using fragment imaging.

PMID- 10060126
TI  - Ab initio calculations of the quasiparticle and absorption spectra of clusters:
      The sodium tetramer.

PMID- 10060127
TI  - Experimental studies of chaos and localization in quantum wave functions.

PMID- 10060128
TI  - Direct observation of transfer of angular momentum to absorptive particles from a
      laser beam with a phase singularity.

PMID- 10060129
TI  - Lattice Boltzmann simulation of nonideal fluids.

PMID- 10060130
TI  - Defect dynamics for spiral chaos in Rayleigh-Benard convection.

PMID- 10060131
TI  - Charging of dust grains in plasma with energetic electrons.

PMID- 10060132
TI  - Ion cyclotron range of frequency heating of a deuterium-tritium plasma via the
      second-harmonic tritium cyclotron resonance.

PMID- 10060133
TI  - Measurements of fast confined alphas on TFTR.

PMID- 10060134
TI  - Collective dynamics in water by high energy resolution inelastic X-ray
      scattering.

PMID- 10060135
TI  - Generalized Gibbs-Thomson equation and surface stiffness for materials with an
      orientational order parameter.

PMID- 10060136
TI  - Low-energy floppy modes in high-temperature ceramics.

PMID- 10060137
TI  - Discontinuous precipitation in the copper-indium system from the viewpoint of
      nuclear 111In probes in grain boundaries.

PMID- 10060139
TI  - Intrinsic localized anharmonic modes at crystal edges.

PMID- 10060138
TI  - Type I band alignment in Si1-xGex/Si(001) quantum wells: photoluminescence under
      applied

PMID- 10060140
TI  - Periodic spinodal decomposition in a binary polymeric fluid mixture.

PMID- 10060142
TI  - Misfit dislocation structure for close-packed metal-metal interfaces.

PMID- 10060141
TI  - Surface structure, lattice dynamics, and Raman spectroscopy of sulphur passivated
      InP(001).

PMID- 10060144
TI  - Bosonization of one-dimensional exclusons and characterization of Luttinger
      liquids.

PMID- 10060143
TI  - Experimental determination of the turning point of thermal energy helium atoms
      above a Cu(001) surface.

PMID- 10060145
TI  - Spectral function of the 1D Hubbard model in the U-->+

PMID- 10060146
TI  - Theory of copper-oxide metals.

PMID- 10060147
TI  - Spectral statistics beyond random matrix theory.

PMID- 10060148
TI  - Magnetic-field-induced metal-insulator transitions in multiple-quantum-well
      structures.

PMID- 10060149
TI  - Global phase diagram for the quantum Hall effect: An experimental picture.

PMID- 10060150
TI  - Lattice effects on the magnetoresistance in doped LaMnO3.

PMID- 10060151
TI  - Interaction coupled cyclotron transitions of two-dimensional electron systems in
      GaAs at high temperatures.

PMID- 10060152
TI  - Evidence for two-dimensional thermal fluctuations of the vortex structure in
      Bi2.15Sr1.85CaCu2O8+ delta from muon spin rotation experiments.

PMID- 10060153
TI  - Evidence for a superfluid density in t-J ladders.

PMID- 10060155
TI  - Impurities in S=1/2 Heisenberg antiferromagnetic chains: Consequences for neutron
      scattering and knight shift.

PMID- 10060154
TI  - Anisotropic ferromagnetic quantum domains.

PMID- 10060156
TI  - Spin dependence of correlations in two-dimensional square-lattice quantum
      Heisenberg antiferromagnets.

PMID- 10060157
TI  - Determination of anomalous superexchange in MnCl2 and its graphite intercalation
      compound.

PMID- 10060158
TI  - Magnetic structures of uranium compounds: Effects of relativity and symmetry.

PMID- 10060159
TI  - Domain structures in ultrathin magnetic films.

PMID- 10060160
TI  - Bubble shape oscillations and the onset of sonoluminescence.

PMID- 10060161
TI  - Viscosity and structural relaxation in suspensions of hard-sphere colloids.

PMID- 10060162
TI  - Neural networks, lattice instantons, and the anti-integrable limit.

PMID- 10060163
TI  - Proportion regulation of biological cells in globally coupled nonlinear systems.

PMID- 10060164
TI  - Comment on "Threshold for dissipative fission"

PMID- 10060165
TI  - Thoennessen and Bertsch reply.

PMID- 10060166
TI  - Comment on "Lagrange equilibrium points in celestial mechanics and nonspreading
      wave packets for strongly driven Rydberg electrons"

PMID- 10060167
TI  - Bialynicki-Birula, Kalinski, and Eberly reply.

PMID- 10060168
TI  - Comment on "From Feynman's wave function to the effective theory of vortex
      dynamics"

PMID- 10060169
TI  - Niu, Ao, and Thouless reply.

PMID- 10060170
TI  - Comment on "Equilibrium properties of a Diblock copolymer Lamellar phase confined
      between flat plates"

PMID- 10060171
TI  - Turner replies.

PMID- 10060172
TI  - Relation of Li(NH3)4 to electrides.

PMID- 10060173
TI  - Comment on "Quasiclassical transport at a van Hove singularity in cuprate
      superconductors"

PMID- 10060174
TI  - Newns et al. reply.

PMID- 10060176
TI  - Ray and Jan reply.

PMID- 10060175
TI  - Comment on "Life at the edge of chaos"

PMID- 10060179
TI  - Stability of matter in magnetic fields.

PMID- 10060180
TI  - Long-time evolution of semiclassical states in anharmonic potentials.

PMID- 10060181
TI  - Renormalized coupling constant for the three-dimensional ising model.

PMID- 10060183
TI  - Finite width effects and gauge invariance in radiative W production and decay.

PMID- 10060182
TI  - Fermions destabilize electroweak strings.

PMID- 10060184
TI  - Measurement of charged and neutral current e-p deep inelastic scattering cross
      sections at high Q2.

PMID- 10060185
TI  - Search for second generation leptoquarks in pp-bar collisions at sqrt s=1.8 TeV.

PMID- 10060186
TI  - Limits on WWZ and WW gamma couplings from WW and WZ production in pp-bar
      collisions at sqrt s=1.8TeV.

PMID- 10060187
TI  - Search for W boson pair production in pp-bar collisions at sqrt s=1.8 TeV.

PMID- 10060188
TI  - Limits on the anomalous ZZ gamma and Z gamma gamma couplings in pp-bar collisions
      at sqrt s=1.8 TeV.

PMID- 10060189
TI  - Measurement of the WW gamma gauge boson couplings in pp-bar collisions at sqrt
      s=1.8 TeV.

PMID- 10060191
TI  - Temperature fluctuations in multiparticle production.

PMID- 10060192
TI  - pi NN coupling from high precision np charge exchange at 162 MeV.

PMID- 10060190
TI  - Probing the nuclear liquid-gas phase transition.

PMID- 10060193
TI  - Contrasting behavior in octupole structures observed at high spin in 220Ra and
      222Th.

PMID- 10060194
TI  - Observation of direct ionization of He by highly charged ions at low velocity.

PMID- 10060195
TI  - Novel time of flight instrument for doppler free kinetic energy release
      spectroscopy.

PMID- 10060196
TI  - Large angle elastic scattering of electrons from Ar+

PMID- 10060197
TI  - Dissociative recombination of HD+ with an ultracold electron beam in a cooler
      ring.

PMID- 10060198
TI  - Chaoticlike behavior in a quantum system without classical counterpart.

PMID- 10060199
TI  - Efficient soft X-ray lasing at 6 to 8 nm with nickel-like lanthanide ions.

PMID- 10060200
TI  - Influence of spatial and temporal laser beam smoothing on stimulated brillouin
      scattering in filamentary laser light.

PMID- 10060201
TI  - Time-dependent channel formation in a laser-produced plasma.

PMID- 10060202
TI  - Effect of collisionality and diamagnetism on the plasma dynamo.

PMID- 10060203
TI  - Internal magnetic turbulence measurement in plasma by cross polarization
      scattering.

PMID- 10060204
TI  - Nonlinear dynamics of stiff polymers.

PMID- 10060205
TI  - Anomalous ion diffusion in dense dipolar liquids.

PMID- 10060206
TI  - Scattering of second sound waves by quantum vorticity.

PMID- 10060207
TI  - Superfluid-insulator transition in 4He films adsorbed in vycor glass.

PMID- 10060208
TI  - Relaxation kinetics of nonlinear systems coupled to a nonequilibrium bath.

PMID- 10060209
TI  - Monte Carlo studies of ternary semiconductor alloys: Application to the Si1-x
      yGexCy system.

PMID- 10060210
TI  - Chemistry and structure of CdO/Ag{222} heterophase interfaces.

PMID- 10060211
TI  - Real time spectroellipsometry study of the evolution of bonding in diamond thin
      films during nucleation and growth.

PMID- 10060212
TI  - Band theory for ground-state properties and excitation spectra of perovskite
      LaMO3 (M=Mn, Fe, Co, Ni).

PMID- 10060213
TI  - Size dependence of excitons in silicon nanocrystals.

PMID- 10060214
TI  - Bulk lattice instability in II-VI semiconductors and its effect on impurity
      compensation.

PMID- 10060215
TI  - Resonant optical second harmonic generation at the steps of vicinal Si(001).

PMID- 10060216
TI  - Manifestations of classical chaos in the energy level spectrum of a quantum well.

PMID- 10060217
TI  - Direct creation of quantum well excitons by electron resonant tunneling.

PMID- 10060218
TI  - Energy gap induced by impurity scattering: New phase transition in anisotropic
      superconductors.

PMID- 10060219
TI  - Parity fluctuations between Coulomb blockaded superconducting islands.

PMID- 10060220
TI  - Nonadiabatic superconductivity: Electron-phonon interaction beyond Migdal's
      theorem.

PMID- 10060221
TI  - Microwave-induced "Somersault effect" in flow of Josephson current through a
      quantum constriction.

PMID- 10060222
TI  - Separation of the irreversibility and melting lines in Bi2Sr2CaCu2O8 crystals.

PMID- 10060223
TI  - Energy barriers to motion of flux lines in random media.

PMID- 10060225
TI  - Antiferromagnetism and its relation to the superconducting phases of UPt3.

PMID- 10060224
TI  - Antiferromagnetic ordering and spin structure in the organic conductor, kappa 
      (BEDT-TTF)2Cu

PMID- 10060226
TI  - Surface states and angle-resolved photoemission spectra from Nd2-xCexCuO4
      superconductor.

PMID- 10060227
TI  - Broken symmetry of two-component nu =1/2 quantum Hall states.

PMID- 10060228
TI  - Glassiness in a Model without Energy Barriers.

PMID- 10060229
TI  - Low-energy excitations and the electronic specific heat of YbBiPt.

PMID- 10060230
TI  - X-ray and neutron scattering, magnetization, and heat capacity study of the 3D
      random field ising model.

PMID- 10060232
TI  - Interference of crossing trigger waves in multilayer reaction-diffusion systems.

PMID- 10060231
TI  - Neutron scattering studies of Y1-xUxPd3 compounds.

PMID- 10060233
TI  - Solitary waves of molecular distributions in liquids generated by electrophoresis
      and optical fields.

PMID- 10060235
TI  - Interaction of multipactor discharge and rf circuit.

PMID- 10060234
TI  - Efficient conversion of the energy of intense relativistic electron beams into rf
      waves.

PMID- 10060236
TI  - Earthquake cycles and neural reverberations: Collective oscillations in systems
      with pulse-coupled threshold elements.

PMID- 10060237
TI  - Novel type of phase transition in a system of self-driven particles.

PMID- 10060239
TI  - Comment on "Direct observation of transition from delayed ionization to direct
      ionization for free C60 and C70: Thermionic emission?"

PMID- 10060238
TI  - Evidence for determinism in ventricular fibrillation.

PMID- 10060243
TI  - Quantum cryptography based on orthogonal states.

PMID- 10060240
TI  - Stuke and Zhang reply.

PMID- 10060244
TI  - Invariant Tori and Heisenberg matrix mechanics: A new window on the quantum
      classical correspondence.

PMID- 10060245
TI  - Confirmation of the asymptotic Bethe Ansatz.

PMID- 10060246
TI  - Young's double-slit interferometry within an atom.

PMID- 10060247
TI  - Black hole singularities: A numerical approach.

PMID- 10060248
TI  - Thermodynamics of spacetime: The Einstein equation of state.

PMID- 10060249
TI  - Field ordering and energy density in texture cosmology.

PMID- 10060250
TI  - In search for signs of chaos in branching processes.

PMID- 10060251
TI  - Enhanced production of low-mass electron pairs in 200 GeV/nucleon S-Au collisions
      at the CERN super proton synchrotron.

PMID- 10060253
TI  - Anharmonic vibrator description of yrast states of rotational and vibrational
      nuclei.

PMID- 10060252
TI  - Effects of pair correlations in statistical gamma -decay spectra.

PMID- 10060254
TI  - Diagonalization of Hamiltonians for many-body systems by auxiliary field quantum
      Monte Carlo technique.

PMID- 10060256
TI  - Nonlinear dynamics of chirped pulse excitation and dissociation of diatomic
      molecules.

PMID- 10060255
TI  - Two-body mechanisms in pion photoproduction on the trinucleon.

PMID- 10060257
TI  - Optical dipole noise of two-level atoms.

PMID- 10060258
TI  - Generation of streamwise vortical structures in bluff body wakes.

PMID- 10060259
TI  - Startup methods for single-mode gyrotron operation.

PMID- 10060260
TI  - Effects of magnetic ripple on lower-hybrid wave propagation.

PMID- 10060262
TI  - Large-scale molecular dynamics study of entangled hard-chain fluids.

PMID- 10060261
TI  - Pressure heating of electrons in capacitively coupled rf discharges.

PMID- 10060263
TI  - Spin-polarization-induced structural selectivity in Pd3X and Pt3X (X=3d)
      compounds.

PMID- 10060265
TI  - Critical behavior of superfluid 4He in aerogel.

PMID- 10060264
TI  - Linear scaling method for phonon calculations from electronic structure.

PMID- 10060266
TI  - Surface freezing in binary mixtures of alkanes: New phases and phase transitions.

PMID- 10060267
TI  - Superhard and elastic carbon nitride thin films having fullerenelike
      microstructure.

PMID- 10060268
TI  - Universal charge and spin response in optimally doped antiferromagnets.

PMID- 10060269
TI  - Quasiparticle dispersion of the 2D Hubbard model: From an insulator to a metal.

PMID- 10060270
TI  - Berry phase, hyperorbits, and the Hofstadter spectrum.

PMID- 10060272
TI  - Mean-field theory of the localization transition of hard-core bosons.

PMID- 10060271
TI  - Electrophonon resonances in mesoscopic structures.

PMID- 10060273
TI  - Sensitivity of quantum chaotic wave-function intensities to changes in external
      perturbations.

PMID- 10060275
TI  - Quantum Hall effect in spin-degenerate Landau levels: Spin-orbit enhancement of
      the conductivity.

PMID- 10060274
TI  - Optical Larmor beat detection of high-resolution nuclear magnetic resonance in a
      semiconductor heterostructure.

PMID- 10060276
TI  - Lorentz contraction of flux quanta observed in experiments with annular Josephson
      tunnel junctions.

PMID- 10060277
TI  - Microscopic description of the vortex state near the upper critical field.

PMID- 10060278
TI  - Vortex entanglement and broken symmetry.

PMID- 10060279
TI  - Charged vortices in high temperature superconductors.

PMID- 10060280
TI  - Spatially varying energy gap in the CuO chains of YBa2Cu3O7-x detected by
      scanning tunneling spectroscopy.

PMID- 10060282
TI  - Exact soliton solutions for a spin chain with an easy plane.

PMID- 10060281
TI  - Violation of Kohler's rule in the normal-state magnetoresistance of YBa2Cu3O7-
      delta and La2SrxCuO4.

PMID- 10060283
TI  - Light scattering study of the coupled soft-optic and acoustic mode in hexagonal
      barium titanate.

PMID- 10060284
TI  - Dark states in coherent semiconductor spectroscopy.

PMID- 10060285
TI  - Transition from linear to nonlinear sputtering of solid xenon.

PMID- 10060286
TI  - Radial electron-beam-breakup transit-time oscillator.

PMID- 10060288
TI  - Comment on "Matched optical solitary waves for three and five level systems"

PMID- 10060287
TI  - Local and global convergence of on-line learning.

PMID- 10060290
TI  - Tanabe and Kaneko reply.

PMID- 10060289
TI  - Comment on "Behavior of a falling paper"

PMID- 10060291
TI  - Comment on "Vortex lattice symmetry and electronic structure in YBa2Cu3O7"

PMID- 10060297
TI  - Monte Carlo Updating of Space-Time Configurations: New Algorithm for Stochastic,
      Classical Dynamics.

PMID- 10060292
TI  - Keimer et al. reply.

PMID- 10060298
TI  - Quantum Particle on a Rotating Loop: Topological Quenching due to a Coriolis
      Aharonov-Bohm Effect.

PMID- 10060300
TI  - Search for Magnetic Monopoles Trapped in Matter.

PMID- 10060299
TI  - Measurement of the Solar Gravitational Deflection of Radio Waves Using Very-Long
      Baseline Interferometry.

PMID- 10060301
TI  - Hadronic Light-by-Light Contribution to the Muon g-2.

PMID- 10060302
TI  - Measurement of the B Meson Differential Cross Section d sigma /dpT in pp-bar
      Collisions at sqrt s=1.8 TeV.

PMID- 10060304
TI  - s-Channel Higgs Boson Production at a Muon-Muon Collider.

PMID- 10060303
TI  - W and Z Boson Production in pp-bar Collisions at sqrt s=1.8 TeV.

PMID- 10060305
TI  - Extraction of the Ratio Fn2/Fp2 from Muon-Deuteron and Muon-Proton Scattering at
      Small x and Q2.

PMID- 10060306
TI  - Identification and Quadrupole-Moment Measurement of a Superdeformed Band in 84Zr.

PMID- 10060307
TI  - Assessing the Evolutionary Nature of Multifragment Decay.

PMID- 10060308
TI  - Decay Paths of Interfering Two-Electron Excitations in Helium.

PMID- 10060309
TI  - Photoionization Experiments with an Atomic Beam of Tungsten in the Region of the
      5p and 4f excitation.

PMID- 10060310
TI  - Nondispersive Electronic Wave Packets in Multiphoton Processes.

PMID- 10060312
TI  - Kinematic Isotope Effects in Low Energy Electron Capture.

PMID- 10060311
TI  - Multiphoton Ionization Enhancement Using Two Phase-Coherent Laser Pulses.

PMID- 10060313
TI  - Experimental Demonstration of Laser Oscillation without Population Inversion via
      Quantum Interference in Rb.

PMID- 10060314
TI  - Statistics of Topological Defects and Spatiotemporal Chaos in a Reaction
      Diffusion System.

PMID- 10060315
TI  - Photonic Band Gaps: Noncommuting Limits and the "Acoustic Band"

PMID- 10060316
TI  - Measurement of the Nonlinear Goos-Hanchen Effect for Gaussian Optical Beams.

PMID- 10060317
TI  - Pump-Probe Experiments with a Single Molecule: ac-Stark Effect and Nonlinear
      Optical Response.

PMID- 10060318
TI  - Stable Coexistence of Spiral and Target Patterns in Freely Suspended Films of
      Smectic-C Liquid Crystals.

PMID- 10060320
TI  - Beam-Photoelectron Interactions in Positron Storage Rings.

PMID- 10060319
TI  - Fluctuations in Quasi-Two-Dimensional Fast Dynamos.

PMID- 10060321
TI  - Opacity of Dense, Cold, and Strongly Coupled Plasmas.

PMID- 10060322
TI  - Coexistence Curve of Poly(dimethylsiloxane)- Poly(ethylmethylsiloxane) Mixture.

PMID- 10060323
TI  - Oscillating Interatomic Potentials and Growth of Icosahedral Quasicrystals.

PMID- 10060324
TI  - Neutrino-Recoil-Induced Frenkel Pairs in InSb Observed by Mossbauer Spectroscopy.

PMID- 10060326
TI  - Exactly Solved Model of Self-Organized Criticality.

PMID- 10060325
TI  - Spectral Statistics of Acoustic Resonances in Aluminum Blocks.

PMID- 10060327
TI  - Density and Temperature Relaxation in the Two-Phase Region near the Critical
      Point of a Pure Fluid.

PMID- 10060328
TI  - Anomalous Phase Separation Kinetics Observed in a Micelle Solution.

PMID- 10060329
TI  - Vortex Core Size in Submonolayer Superfluid 4He Films.

PMID- 10060330
TI  - Rotationally Resolved Spectroscopy of SF6 in Liquid Helium Clusters: A Molecular
      Probe of Cluster Temperature.

PMID- 10060331
TI  - Enhanced Step Waviness on SiGe(001)-(2 x 1) Surfaces under Tensile Strain.

PMID- 10060333
TI  - Strongly Inhomogeneous Surface Growth on Polymers.

PMID- 10060332
TI  - Single Jump Mechanisms for Large Cluster Diffusion on Metal Surfaces.

PMID- 10060334
TI  - Step Instabilities: A New Kinetic Route to 3D Growth.

PMID- 10060335
TI  - Self-Organized Formation of Compositionally Modulated ZnSe1-xTex Superlattices.

PMID- 10060336
TI  - Tunneling Ionization of Autolocalized DX- Centers in Terahertz Fields.

PMID- 10060337
TI  - Radioactive Isotopes in Photoluminescence Experiments: Identification of Defect
      Levels.

PMID- 10060338
TI  - h/2e Oscillations for Correlated Electron Pairs in Disordered Mesoscopic Rings.

PMID- 10060339
TI  - Enhancement of Orbital Magnetism at Surfaces: Co on Cu(100).

PMID- 10060341
TI  - Shot-Noise Suppression in the Single-Electron Tunneling Regime.

PMID- 10060340
TI  - Be Delta-Doped Layers in GaAs Imaged with Atomic Resolution Using Scanning
      Tunneling Microscopy.

PMID- 10060342
TI  - Observation of Resonant Tunneling between Macroscopically Distinct Quantum
      Levels.

PMID- 10060344
TI  - Theory of One-Channel versus Multichannel Kondo Effects for Ce3+ Impurities.

PMID- 10060343
TI  - Interface Delocalization Transition in Type-I Superconductors.

PMID- 10060345
TI  - Direct Observation of a Magnetic Gap in Superconducting La1.85Sr0.15CuO4
      (Tc=37.3K).

PMID- 10060346
TI  - Competing Instabilities and the High Field Phases of (TMTSF)2ClO4.

PMID- 10060347
TI  - Determination of Magnetostrictive Stresses in Magnetic Rare-Earth Superlattices
      by a Cantilever Method.

PMID- 10060348
TI  - Spin Density Wave Instability for Chromium in Fe/Cr(100) Multilayers.

PMID- 10060349
TI  - Conversion Electron Mossbauer Spectroscopy Study of Epitaxial beta -FeSi2 Grown
      by Molecular Beam Epitaxy.

PMID- 10060350
TI  - Raman Study of Cluster Dynamics in Disordered Ferroelectrics.

PMID- 10060351
TI  - Quantum Channeling Effects for 1 MeV Positrons.

PMID- 10060353
TI  - Boltzmann Fluctuations in Numerical Simulations of Nonequilibrium Lattice
      Threshold Systems.

PMID- 10060352
TI  - Trajectory-Dependent Charge Exchange in Alkali Ion Scattering from a Clean Metal
      Surface.

PMID- 10060354
TI  - Experimental Phase Diagram of a Binary Colloidal Hard-Sphere Mixture with a Large
      Size Ratio.

PMID- 10060355
TI  - Folding Transitions of Self-Avoiding Membranes.

PMID- 10060356
TI  - Silicon-Neuron Junction: Capacitive Stimulation of an Individual Neuron on a
      Silicon Chip.

PMID- 10060357
TI  - Comment on "Monte Carlo Simulations of Phase Separation in Chemically Reactive
      Binary Mixtures"

PMID- 10060359
TI  - Comment on "Superconducting Pairing Symmetry and Josephson Tunneling"

PMID- 10060358
TI  - Glotzer, Stauffer, and Jan Reply.

PMID- 10060360
TI  - Xu et al. Reply.

PMID- 10060361
TI  - Comment on "Quenching of the Nonlinear Susceptibility at a T=0 Spin Glass
      Transition"

PMID- 10060362
TI  - Bitko, Rosenbaum, and Aeppli Reply.

PMID- 10060365
TI  - New Method of Solving the Traveling Salesman Problem Based on Real Space
      Renormalization Theory.

PMID- 10060366
TI  - Evidence of Bose-Einstein Condensation in an Atomic Gas with Attractive
      Interactions.

PMID- 10060367
TI  - Reentrance Phenomena in Noise Induced Transitions.

PMID- 10060368
TI  - Electroweak Baryogenesis from a Classical Force.

PMID- 10060369
TI  - Coulomb Phase of N=2 Supersymmetric QCD.

PMID- 10060370
TI  - CP Asymmetry Relations between B-bar0--> pi pi and B-bar0--> pi K Rates.

PMID- 10060371
TI  - Glueballs and Instantons.

PMID- 10060372
TI  - Precision Measurement of Charge Symmetry Breaking in <?PubEqn>np Elastic
      Scattering at 347 MeV.

PMID- 10060373
TI  - Charge State Blocking of K-Shell Internal Conversion in 125Te.

PMID- 10060375
TI  - Transient Molecular-Ion Formation in Rydberg-Electron Capture.

PMID- 10060376
TI  - Structure of Binary Quantum Clusters.

PMID- 10060374
TI  - Study of the Unstable Nucleus 10Li in Stripping Reactions of the Radioactive
      Projectiles 11Be and 11Li.

PMID- 10060377
TI  - Temperature Dependence of the Optical Response of Small, Open Shell Sodium
      Clusters.

PMID- 10060378
TI  - Chaos in Andreev Billiards.

PMID- 10060379
TI  - Coherent Backscattering of Light from Amplifying Random Media.

PMID- 10060381
TI  - Stability of a Solitary Pulse against Wave Packet Disturbances in an Active
      Medium.

PMID- 10060380
TI  - Thermally Induced Fluctuations below the Onset of Rayleigh-Benard Convection.

PMID- 10060382
TI  - k Spectrum of Passive Scalars in Lagrangian Chaotic Fluid Flows.

PMID- 10060384
TI  - Dynamics of Core Electron Temperature Fluctuations during Sawtooth Oscillations
      on TEXT-U.

PMID- 10060383
TI  - Intense Far-Infrared Free-Electron Laser Pulses with a Length of Six Optical
      Cycles.

PMID- 10060385
TI  - High- beta Disruption in Tokamaks.

PMID- 10060386
TI  - Dynamic Evolution of Pyramid Structures during Growth of Epitaxial Fe(001) Films.

PMID- 10060387
TI  - Atomic Structure of the c(4 x 2) Surface Reconstruction of Ge(001) as Determined
      by X-Ray Diffraction.

PMID- 10060388
TI  - Hysteresis and Instability of a Driven Interface in a Periodic Potential.

PMID- 10060389
TI  - Microscopic Structure and Intermolecular Potential in Liquid Deuterium.

PMID- 10060391
TI  - Diffusion and Drift of Charge Carriers in Molecularly Doped Polymers.

PMID- 10060390
TI  - Glass States and Freezing Transition in (NH4I)x(KI)1-x.

PMID- 10060392
TI  - Phase Separation Dynamics under Stirring.

PMID- 10060394
TI  - Pumping Liquid Crystals.

PMID- 10060393
TI  - Driven Interfaces with Phase Disorder.

PMID- 10060395
TI  - Phase Diagram and Orientational Order in a Biaxial Lattice Model: A Monte Carlo
      Study.

PMID- 10060396
TI  - Zn under Pressure: A Singularity in the hcp Structure at c/a= sqrt 3.

PMID- 10060397
TI  - Signatures of Bulk and Surface Arsenic Antisite Defects in GaAs(110).

PMID- 10060398
TI  - Impulsive Softening of Coherent Phonons in Tellurium.

PMID- 10060400
TI  - Quantum Magnetism of CuGeO3.

PMID- 10060399
TI  - Anharmonic Phonon Lifetimes in Semiconductors from Density-Functional
      Perturbation Theory.

PMID- 10060401
TI  - Observation of Plasmon-Optic Phonon Coupled Modes in GaAs/AlGaAs Resonant
      Tunneling Structures via Acoustic Phonon Decay Products.

PMID- 10060402
TI  - ac Josephson Effect in a Single Quantum Channel.

PMID- 10060403
TI  - Nature of the Irreversibility Line in High-Temperature Superconductors.

PMID- 10060404
TI  - Magnetic Domain Structure in Ultrathin Films.

PMID- 10060405
TI  - Evidence of a Surface-Mediated Magnetically Induced Miscibility Gap in Co-Pt
      Alloy Thin Films.

PMID- 10060407
TI  - Long-Range Electrostatic Attraction between Similar, Charge-Neutral Walls.

PMID- 10060406
TI  - Giant Near-90 degrees Coupling in Epitaxial CoFe/Mn/CoFe Sandwich Structures.

PMID- 10060408
TI  - Scattering and Imaging with Diffusing Temporal Field Correlations.

PMID- 10060410
TI  - Neurocomputation by Reaction Diffusion.

PMID- 10060409
TI  - Aggregation Patterns in Stressed Bacteria.

PMID- 10060411
TI  - Comment on "Absorption of Sound by Vortex Filaments"

PMID- 10060413
TI  - Comment on "3D X-Y Scaling of the Specific Heat of YBa2Cu3O7- delta Single
      Crystals"

PMID- 10060412
TI  - Nazarenko Replies.

PMID- 10060414
TI  - Overend, Howson, and Lawrie Reply.

PMID- 10060419
TI  - Minimum decision cost for quantum ensembles.

PMID- 10060420
TI  - Ground-state properties of magnetically trapped Bose-condensed rubidium gas.

PMID- 10060422
TI  - Surface critical phenomena and scaling in the eight-vertex model.

PMID- 10060421
TI  - Superfluidity of spin-polarized 6Li.

PMID- 10060423
TI  - First phase-coherent frequency measurement of visible radiation.

PMID- 10060424
TI  - Study of Lambda 0 polarization in pp-->p Lambda 0K+ pi + pi - pi + pi - at 27.5
      GeV.

PMID- 10060425
TI  - First study of heavy-ion mirror charge exchange.

PMID- 10060427
TI  - Temperature and density mapping of supersonic jet expansions using linear Raman
      spectroscopy.

PMID- 10060426
TI  - First experimental determination and theoretical calculation of partial
      photoionization cross sections of lithium over the energy region of hollow Atomic
      States.

PMID- 10060428
TI  - Do solitons exchange conserved quantities during collisions?

PMID- 10060430
TI  - Square patterns in Benard-Marangoni convection.

PMID- 10060429
TI  - Criticality in droplet fragmentation.

PMID- 10060431
TI  - Harmonic generation by femtosecond laser-solid interaction: A coherent "water
      window" light source?

PMID- 10060433
TI  - Theory of chiral order in random copolymers.

PMID- 10060432
TI  - Localized magnetism in molten icosahedral and approximant AlPdMn phases.

PMID- 10060434
TI  - Mode coupling theory and the glass transition in molecular dynamics simulated
      NiZr.

PMID- 10060436
TI  - Non-Arrhenius conductivity in glass: Mobility and conductivity saturation
      effects.

PMID- 10060435
TI  - Medium-range order in silica, the canonical network glass.

PMID- 10060437
TI  - Structure of deuterated phase-IV ammonia.

PMID- 10060438
TI  - Exact distribution of energies in the two-dimensional ising model.

PMID- 10060439
TI  - Self-consistent-field lattice gas model for the surface ordering transition of n
      hexadecane.

PMID- 10060440
TI  - Microscopic model of upward creep of an ultrathin wetting film.

PMID- 10060441
TI  - Theory for the (1 x 1) rumpled relaxations at TiC(001) and TaC(001) surfaces.

PMID- 10060442
TI  - Dynamical step edge stiffness on the Si(111) surface.

PMID- 10060443
TI  - Experimental observation of ballistic atom exchange on metal surfaces.

PMID- 10060444
TI  - van der Waals interactions in density-functional theory.

PMID- 10060445
TI  - Observation of a magnetic-field-induced transition in the behavior of extremely
      shallow quantum well excitons.

PMID- 10060446
TI  - Transmission through a quantum dot in an Aharonov-Bohm ring.

PMID- 10060447
TI  - Aharonov-Bohm oscillations and resonant tunneling in strongly correlated quantum
      dots.

PMID- 10060448
TI  - Numerical tests of the chiral Luttinger liquid theory for fractional Hall edges.

PMID- 10060449
TI  - Angular dependence of the c-axis normal state magnetoresistance in single crystal
      Tl2Ba2CuO6.

PMID- 10060450
TI  - In-plane and out-of-plane optical spectra of Sr2RuO4.

PMID- 10060452
TI  - Superfluid anisotropy in YBCO: Evidence for pair tunneling superconductivity.

PMID- 10060451
TI  - Long-range coherence in a mesoscopic metal near a superconducting interface.

PMID- 10060453
TI  - Negative local permeability in Bi2Sr2CaCu2O8 crystals.

PMID- 10060454
TI  - Nucleation and growth of the normal phase in thin superconducting strips.

PMID- 10060455
TI  - Geometry of developing flame fronts: Analysis with pole decomposition.

PMID- 10060456
TI  - Phase behavior of small attractive colloidal particles.

PMID- 10060457
TI  - Extraction of 1 GW of rf power from an injection locked relativistic klystron
      oscillator.

PMID- 10060458
TI  - Comment on "Theory of spinodal decomposition"

PMID- 10060460
TI  - Finite-size scaling and universality above the upper critical dimensionality.

PMID- 10060461
TI  - Salty water Cerenkov detectors for solar neutrinos.

PMID- 10060462
TI  - New scenario for string unification.

PMID- 10060463
TI  - Measurement of the B semileptonic branching fraction with lepton tags.

PMID- 10060464
TI  - Confirmation of the sigma meson.

PMID- 10060465
TI  - Measurement of the longitudinal, transverse, and longitudinal-transverse
      structure functions in the 2H(e,e'p)n reaction.

PMID- 10060467
TI  - Experimental fusion barrier distributions reflecting projectile octupole state
      coupling to prolate and oblate target nuclei.

PMID- 10060466
TI  - Excitation energies and spins of a superdeformed band in 194Hg from one-step
      discrete decays to the yrast line.

PMID- 10060468
TI  - Extensive electron-nuclear angular momentum exchange in vibrational
      autoionization of np and nf Rydberg states of NO.

PMID- 10060470
TI  - How "magic" is a magic metal cluster?

PMID- 10060469
TI  - Positronium-argon scattering.

PMID- 10060471
TI  - Wigner random banded matrices with sparse structure: Local spectral density of
      states.

PMID- 10060473
TI  - Coherent and incoherent quantum stochastic resonance.

PMID- 10060472
TI  - Manifestation of classical bifurcation in the spectrum of the integrable quantum
      dimer.

PMID- 10060474
TI  - Penumbra diffraction in the quantization of dispersing billiards.

PMID- 10060476
TI  - Optical bullet holes: Robust controllable localized states of a nonlinear cavity.

PMID- 10060475
TI  - Spiral waves in chaotic systems.

PMID- 10060477
TI  - Bragg grating solitons.

PMID- 10060478
TI  - New scenario for transition to turbulence?

PMID- 10060479
TI  - Electron acceleration by a transverse electromagnetic wave supplemented with a
      crossed static magnetic field.

PMID- 10060480
TI  - How a wave flips its energy sign by linear conversion.

PMID- 10060482
TI  - Mode conversion heating experiments on the Tore Supra tokamak.

PMID- 10060481
TI  - Measurement and simulation of laser imprinting and consequent Rayleigh-Taylor
      growth.

PMID- 10060483
TI  - An explanation of the density maximum in water.

PMID- 10060484
TI  - Nonlinear effects in vibrating smectic films.

PMID- 10060485
TI  - Separating thermal, electronic, and topographic effects in pulsed laser melting
      and sputtering of gold.

PMID- 10060486
TI  - Extended infrared studies of high pressure hydrogen.

PMID- 10060488
TI  - Cs-induced relaxation of the Cu(110) surface.

PMID- 10060487
TI  - Synchrotron infrared spectroscopy to 0.15 eV of H2 and D2 at megabar pressures.

PMID- 10060489
TI  - Self-organization in growth of quantum dot superlattices.

PMID- 10060490
TI  - Kinetic pathways of order-disorder and order-order transitions in weakly
      segregated microstructured systems.

PMID- 10060491
TI  - Equilibrium dynamics of the dissipative two-state system.

PMID- 10060492
TI  - Dimensionality dependence of the metal-insulator transition in the Anderson model
      of localization.

PMID- 10060493
TI  - One-center small polarons as short-lived precursors in self-trapping processes of
      holes and electron-hole pairs in alkali iodides.

PMID- 10060494
TI  - Non-Gaussian distribution of Coulomb blockade peak heights in quantum dots.

PMID- 10060495
TI  - Statistics and parametric correlations of Coulomb blockade peak fluctuations in
      quantum dots.

PMID- 10060496
TI  - Coherent control of photocurrent generation in bulk semiconductors.

PMID- 10060497
TI  - Haldane's fractional statistics and the lowest Landau level on a torus.

PMID- 10060498
TI  - Universal parametric correlations of conductance peaks in quantum dots.

PMID- 10060499
TI  - Zero-bias anomalies and boson-assisted tunneling through quantum dots.

PMID- 10060501
TI  - Linear ac response of thin superconductors during flux creep.

PMID- 10060500
TI  - Field dependence of c-axis plasma resonance in Josephson-coupled superconductors.

PMID- 10060502
TI  - Proximity effects in superconductor/insulating-ferromagnet NbN/GdN multilayers.

PMID- 10060503
TI  - Spin dynamics of hole doped Y2-xCxBaNiO5.

PMID- 10060504
TI  - Singlet semiconductor to ferromagnetic metal transition in FeSi.

PMID- 10060505
TI  - Energetic and thermodynamic aspects of hysteresis.

PMID- 10060506
TI  - Finite-size effects and uncompensated magnetization in thin antiferromagnetic CoO
      layers.

PMID- 10060507
TI  - Dephasing-rephasing balancing in photon echoes by excitation induced frequency
      shifts.

PMID- 10060508
TI  - Adsorbate-localized excitation in surface photochemistry: Methane on Pt(111).

PMID- 10060510
TI  - Comment on "Overdamped phonons in fluid helium at 4 K"

PMID- 10060509
TI  - Rapid phase locking in systems of pulse-coupled oscillators with delays.

PMID- 10060511
TI  - Crevecoeur, de Schepper, and Montfrooij reply.

PMID- 10060512
TI  - Core hole effects in resonant inelastic x-ray scattering of graphite.

PMID- 10060515
TI  - Dimensional Hausdorff properties of singular continuous spectra.

PMID- 10060513
TI  - Carlisle et al. reply.

PMID- 10060516
TI  - Geometric phase in quantum billiards with a pointlike scatterer.

PMID- 10060517
TI  - Spectrum of light scattered from a weakly interacting Bose-Einstein condensed
      gas.

PMID- 10060518
TI  - Creation of strange matter at low initial microT.

PMID- 10060520
TI  - Streak-camera probing of rubidium Rydberg wave packet decay in an electric field.

PMID- 10060519
TI  - Constraint satisfaction in local and gradient susceptibility approximations:
      Application to a van der Waals density functional.

PMID- 10060521
TI  - Gauge structures in atom-laser interaction: Bloch oscillations in a dark lattice.

PMID- 10060522
TI  - Molecular dynamics simulation for the formation of magic-number clusters with a
      Lennard-Jones potential.

PMID- 10060523
TI  - Generation of nonclassical motional states of a trapped atom.

PMID- 10060524
TI  - Quantum Rabi oscillation: A direct test of field quantization in a cavity.

PMID- 10060525
TI  - Phase synchronization of chaotic oscillators.

PMID- 10060526
TI  - Universal scaling law for the largest Lyapunov exponent in coupled map lattices.

PMID- 10060527
TI  - Lyapunov exponent of a many body system and its transport coefficients.

PMID- 10060528
TI  - Generalized synchronization, predictability, and equivalence of unidirectionally
      coupled dynamical systems.

PMID- 10060529
TI  - Quantum kinetics of semiconductor light emission and lasing.

PMID- 10060530
TI  - Threshold dynamics of singular gravity-capillary waves.

PMID- 10060531
TI  - Extended self-similarity in turbulent systems: An analytically soluble example.

PMID- 10060532
TI  - Efficient extreme UV harmonics generated from picosecond laser pulse interactions
      with solid targets.

PMID- 10060533
TI  - Frequency separation method for relaxation problems.

PMID- 10060534
TI  - Wall association and recirculation in expanding thermal arc plasmas.

PMID- 10060535
TI  - Frozen phases of random heteropolymers in disordered media.

PMID- 10060536
TI  - Rough growth and morphological instability of compact electrodeposits.

PMID- 10060537
TI  - Crystal symmetry lowering at an order-disorder transition.

PMID- 10060538
TI  - Resonant-coherent excitation of channeled ions.

PMID- 10060539
TI  - Metallization of fluid molecular hydrogen at 140 GPa (1.4 Mbar).

PMID- 10060540
TI  - Spectral signature of low temperature hopping between two impurity-induced
      elastic configurations.

PMID- 10060541
TI  - Electrothermal effect in nematic liquid crystal.

PMID- 10060542
TI  - Study of the dynamic structure factor in the beta relaxation regime of
      polybutadiene.

PMID- 10060544
TI  - Fluctuative mechanism of vortex nucleation in the flow of 4He.

PMID- 10060543
TI  - Thermal expansion study of ordered and disordered Fe3Al: An effective approach
      for the determination of vibrational entropy.

PMID- 10060545
TI  - Heat capacity study of the quantum antiferromagnetism of a 3He monolayer.

PMID- 10060547
TI  - Formation of surface ternary alloys by coadsorption of alkali metals on Al(111).

PMID- 10060546
TI  - Tip-assisted diffusion on Ag(110) in scanning tunneling microscopy.

PMID- 10060548
TI  - Semiclassical limits of the spectrum of Harper's equation.

PMID- 10060549
TI  - Direct measurement of conjugated polymer electronic excitation energies using
      metal/polymer/metal structures.

PMID- 10060550
TI  - Resonant polaron coupling of high index electron Landau levels in GaAs
      heterostructures.

PMID- 10060551
TI  - Polarizability of small metal particles: "Weak localization" effects.

PMID- 10060552
TI  - Multivalley electron population dynamics on the Ge(111):As surface.

PMID- 10060553
TI  - Resonant photon-assisted tunneling through a double quantum dot: An electron pump
      from spatial Rabi oscillations.

PMID- 10060554
TI  - Quasiparticle tunneling properties of planar YBa2Cu3O7- delta /PrBa2Cu3O7- delta
      /HoBa2Cu3O7- delta heterostructures.

PMID- 10060555
TI  - Meissner-like response of type-II superconductors in the mixed state.

PMID- 10060556
TI  - Thermal depinning of flux lines in HgBa2CuO4+ delta from 199Hg spin-lattice
      relaxation.

PMID- 10060557
TI  - Plaquette resonating-valence-bond ground state of CaV4O9.

PMID- 10060558
TI  - Local magnetism and crystal fields of Pr in PrBa2Cu3O7 studied by 141Pr NMR.

PMID- 10060560
TI  - Evidence for a direct d-d hybridization mechanism for the interlayer exchange
      coupling in epitaxial Co/Mn multilayers.

PMID- 10060559
TI  - Morphology-induced oscillations of the magnetic anisotropy in ultrathin Co films.

PMID- 10060561
TI  - Spatiotemporal near-field spin microscopy in patterned magnetic heterostructures.

PMID- 10060562
TI  - Plasmon dispersion and damping at the surface of a semimetal.

PMID- 10060563
TI  - Wave-unlocking transition in resonantly coupled complex Ginzburg-Landau
      equations.

PMID- 10060564
TI  - Surface enhanced photodissociation of physisorbed molecules.

PMID- 10060566
TI  - Negative resistance and rectification in Brownian transport.

PMID- 10060565
TI  - Mean field approach to Bayes learning in feed-forward neural networks.

PMID- 10060567
TI  - Comment on "Amplification under the standard quantum limit"

PMID- 10060569
TI  - Comment on "Exact results on scaling exponents in the 2D enstrophy cascade"

PMID- 10060568
TI  - D'Ariano et al. Reply.

PMID- 10060570
TI  - Eyink Replies.

PMID- 10060571
TI  - Can Zipf distinguish language from noise in noncoding DNA?

PMID- 10060572
TI  - No signs of hidden language in noncoding DNA.

PMID- 10060573
TI  - Comment on "Linguistic features of noncoding DNA sequences"

PMID- 10060578
TI  - Observation of moving wave packets reveals their quantum state.

PMID- 10060574
TI  - Mantegna et al. reply.

PMID- 10060579
TI  - Globally uniform semiclassical expressions for time-independent wave functions.

PMID- 10060580
TI  - Emissivities of neutrinos in neutron star cores.

PMID- 10060581
TI  - Dynamical determination of the fundamental couplings in supergravity models.

PMID- 10060582
TI  - Searching for invisible and almost invisible particles at e+e- colliders.

PMID- 10060583
TI  - Search for gluino and squark cascade decays at the Fermilab tevatron collider.

PMID- 10060584
TI  - Glueball spectroscopy in a relativistic many-body approach to hadronic structure.

PMID- 10060585
TI  - Reconstruction of B0-->J/ psi K0S and measurement of ratios of branching ratios
      involving B-->J/ psi K* and B+-->J/ psi K+

PMID- 10060587
TI  - Giant dipole resonance built on highly excited states of 120Sn nuclei populated
      by inelastic alpha scattering.

PMID- 10060586
TI  - Production of phi mesons in central 28Si+196Au collisions at 14.6A GeV/c.

PMID- 10060588
TI  - First observation of the scissors mode in a gamma -soft nucleus: The case of
      196Pt.

PMID- 10060589
TI  - Polarization dependence of optical suppression in photoassociative ionization
      collisions in a sodium magneto-optic trap.

PMID- 10060590
TI  - Laser cooling in the condensed phase by frequency up-conversion.

PMID- 10060591
TI  - Spin exchange and recombination in a gas of atomic hydrogen at 1.2 K.

PMID- 10060593
TI  - Observation of superradiant and subradiant spontaneous emission of two trapped
      ions.

PMID- 10060592
TI  - Synchronous collapses and revivals of atomic dipole fluctuations and photon Fano
      factor beyond the standard quantum limit.

PMID- 10060594
TI  - Laser oscillation without population inversion in a sodium atomic beam.

PMID- 10060595
TI  - Suppression of chaos in a simplified nonlinear dynamo model.

PMID- 10060596
TI  - Identification of intermittent ordered patterns as heteroclinic connections.

PMID- 10060597
TI  - Observation of energy transfer between frequency-mismatched laser beams in a
      large-scale plasma.

PMID- 10060598
TI  - Heating mode transition induced by a magnetic field in a capacitive rf discharge.

PMID- 10060600
TI  - Dynamics, spin fluctuations, and bonding in liquid silicon.

PMID- 10060599
TI  - Laser injection of ultrashort electron pulses into Wakefield plasma waves.

PMID- 10060601
TI  - Anisotropic a-C:H from compression of polyacetylene.

PMID- 10060602
TI  - Two-level system dynamics in the long-time limit: A power-law time dependence.

PMID- 10060604
TI  - Formation of avalanches and critical exponents in an Abelian sandpile model.

PMID- 10060603
TI  - Direct determination of the interaction between vacancies on InP(110) surfaces.

PMID- 10060605
TI  - Ordering and roughening during the epitaxial growth of alloys.

PMID- 10060606
TI  - Critical behavior of n-vector spins derived from cluster structure.

PMID- 10060607
TI  - Parametric generation of second sound by first sound in superfluid helium.

PMID- 10060608
TI  - High-temperature study of the Schwoebel effect in Au(111).

PMID- 10060609
TI  - Decay of two-dimensional Ag islands on Ag(111).

PMID- 10060610
TI  - Energy dissipation in dynamic fracture.

PMID- 10060611
TI  - Chiral conductivities of nanotubes.

PMID- 10060612
TI  - Spin fluctuations in (Y0.97Sc0.03)Mn2: A geometrically frustrated, nearly
      antiferromagnetic, itinerant electron system.

PMID- 10060613
TI  - Fluctuations of transmission distribution in disordered conductors.

PMID- 10060614
TI  - Low temperature dynamics of an Nf-flavor two level system in a metal: Equivalence
      with the Nf-channel Kondo model to 1/N2f order.

PMID- 10060615
TI  - Linear temperature dependence of electrical resistivity in a single-impurity
      model.

PMID- 10060616
TI  - CO chemisorption at metal surfaces and overlayers.

PMID- 10060618
TI  - Inductive probing of the integer quantum Hall effect.

PMID- 10060617
TI  - Giant backscattering magnetoresistance resonance and quantum dot electronic
      structure.

PMID- 10060619
TI  - Skyrmions without sigma models in quantum Hall ferromagnets.

PMID- 10060620
TI  - Study of the SiO2-Si interface using variable energy positron two-dimensional
      angular correlation of annihilation radiation.

PMID- 10060621
TI  - Pair tunneling from c-axis YBa2Cu3O7-x to Pb: Evidence for s-wave component from
      microwave induced steps.

PMID- 10060622
TI  - Doped planar quantum antiferromagnets with striped phases.

PMID- 10060623
TI  - Charge and magnetic order in La0.5Sr1.5MnO4.

PMID- 10060624
TI  - Dynamics in the S=1 one-dimensional antiferromagnet AgVP2S6 via 31P and 51V NMR.

PMID- 10060625
TI  - Novel approach to the analysis of broadband dielectric spectra.

PMID- 10060626
TI  - Electronic excitation during sputtering of silver atoms.

PMID- 10060627
TI  - Systematic derivation of a rotationally covariant extension of the two
      dimensional Newell-Whitehead-Segel equation.

PMID- 10060628
TI  - Unsupervised learning by examples: On-line versus off-line.

PMID- 10060629
TI  - Avalanches in the lung: A statistical mechanical model.

PMID- 10060630
TI  - Comment on "Correlation inequalities and hidden variables"

PMID- 10060631
TI  - Mermin and Garg reply.

PMID- 10060632
TI  - Comment on "Sheared flow stabilization of the m=1 kink mode in Z pinches"

PMID- 10060633
TI  - Shumlak and Hartman reply.

PMID- 10060634
TI  - Comment on "Nucleation and wetting near surface spinodals"

PMID- 10060635
TI  - Bonn and Indekeu reply.

PMID- 10060640
TI  - Off-diagonal long-range order, restricted gauge transformations, and Aharonov
      Bohm effect in conductors.

PMID- 10060641
TI  - Extreme state of a charged black hole in a grand canonical ensemble.

PMID- 10060642
TI  - Universality and clustering in 1+1 dimensional superstring-bit models.

PMID- 10060643
TI  - Hierarchies and textures in supergravity unification.

PMID- 10060644
TI  - Search for light top squarks in pp-bar collisions at sqrt s=1.8 TeV.

PMID- 10060646
TI  - Breakdown of conventional factorization for isolated photon cross sections.

PMID- 10060647
TI  - Power corrections in QCD: A matter of energy resolution.

PMID- 10060645
TI  - Search for W-tilde1Z-tilde2 production via trilepton final states in pp-bar
      collisions at sqrt s=1.8 TeV.

PMID- 10060648
TI  - Unified description of NN and YN interactions in a quark model with effective
      meson-exchange potentials.

PMID- 10060650
TI  - Core hole double-excitation and atomiclike Auger decay in N2.

PMID- 10060649
TI  - Measured magnetic moments and shape coexistence in the neutron-deficient nuclei
      184,186,188Pt.

PMID- 10060651
TI  - Optimal periodic orbits of chaotic systems.

PMID- 10060653
TI  - Propagation of dark stripe beams in nonlinear media: Snake instability and
      creation of optical vortices.

PMID- 10060652
TI  - Transition from Poisson regularity to chaos in a time-reversal noninvariant
      system.

PMID- 10060654
TI  - Observation of spontaneous spin polarization in an optically pumped cesium vapor.

PMID- 10060656
TI  - Evidence for poloidal asymmetry of core electron temperature fluctuations in the
      Texas experimental tokamak.

PMID- 10060655
TI  - Nature of magnetic dynamo growth in the high magnetic Reynolds number limit.

PMID- 10060657
TI  - Simultaneous measurements of hard x-rays and second harmonic emission in fs laser
      target interactions.

PMID- 10060658
TI  - Formation of a composite pinch.

PMID- 10060659
TI  - First evidence of collective alpha particle effect on toroidal Alfven eigenmodes
      in the TFTR D-T experiment.

PMID- 10060660
TI  - Controlling the chaotic regime of nonlinear ionization waves using the time-delay
      autosynchronization method.

PMID- 10060661
TI  - Squeezed phonon states: Modulating quantum fluctuations of atomic displacements.

PMID- 10060662
TI  - Quantum wells and electron interference phenomena in Al due to subsurface noble
      gas bubbles.

PMID- 10060663
TI  - Atomic-sized metallic contacts: Mechanical properties and electronic transport.

PMID- 10060664
TI  - Direct tests of microscopic growth models using hot scanning tunneling microscopy
      movies.

PMID- 10060665
TI  - Low-density fluid phase of dipolar hard spheres.

PMID- 10060666
TI  - Ground state structural anomalies in cuprous halides: CuCl.

PMID- 10060667
TI  - Dynamic crack processes via molecular dynamics.

PMID- 10060668
TI  - Zippering and intermeshing: Novel phase diagrams for interfaces and films.

PMID- 10060669
TI  - Transitions in nonconserving models of self-organized criticality.

PMID- 10060670
TI  - Static freezing transition at a finite temperature in a quasi-one-dimensional
      deuteron glass.

PMID- 10060671
TI  - Excess low temperature specific heat and related phonon density of states in a
      modulated incommensurate dielectric.

PMID- 10060672
TI  - Mixed alkali effect in crystals of beta - and beta "-alumina structure.

PMID- 10060674
TI  - Polarity effect of electromigration in Ni2Si contacts on Si.

PMID- 10060673
TI  - Ga self-diffusion in GaAs isotope heterostructures.

PMID- 10060675
TI  - Triple point dewetting transitions of helium mixtures on cesium.

PMID- 10060677
TI  - Strain relief at metal interfaces with square symmetry.

PMID- 10060676
TI  - Nanoparticle arrays in freely suspended vitrified films.

PMID- 10060678
TI  - Dynamics and nucleation of Si Ad-dimers on the Si(100) surface.

PMID- 10060680
TI  - Geometric phase in Jahn-Teller crystals.

PMID- 10060679
TI  - Atomic processes in low temperature Pt-dendrite growth on Pt(111).

PMID- 10060681
TI  - Renormalization of the Drude conductivity by the electron-phonon interaction.

PMID- 10060682
TI  - Spin-orbit-induced magnetic anisotropy for impurities in metallic samples of
      reduced dimensions: Finite size dependence in the Kondo effect.

PMID- 10060684
TI  - Impurity states and the absence of quasiparticle localization in disordered d
      wave superconductors.

PMID- 10060683
TI  - Undressing a collective intersubband excitation in a quantum well.

PMID- 10060685
TI  - Large time out-of-equilibrium dynamics of a manifold in a random potential.

PMID- 10060686
TI  - Nonequilibrium dynamics following a quench to the critical point in a semi
      infinite system.

PMID- 10060687
TI  - Goldstone modes and low-frequency dynamics of incommensurate chromium alloys.

PMID- 10060689
TI  - Baker and Kawashima reply.

PMID- 10060688
TI  - Comment on "Renormalized coupling constant for the three-dimensional ising model"

PMID- 10060690
TI  - Comment on "Generalized field propagator for electromagnetic scattering and light
      confinement"

PMID- 10060692
TI  - Time-frequency transfer with quantum fields.

PMID- 10060691
TI  - Martin, Girard, and Dereux reply.

PMID- 10060693
TI  - Subthreshold pion dynamics as a source for hard photons beyond proton-neutron
      Bremsstrahlung in heavy-ion collisions.

PMID- 10060695
TI  - Monte Carlo computation of pair correlations in excited nuclei.

PMID- 10060694
TI  - Neutron drops and Skyrme energy-density functionals.

PMID- 10060696
TI  - Onset and near threshold evolution of the Cu K alpha x-ray satellites.

PMID- 10060697
TI  - Observation of temporal behavior of an atomic wave packet localized in an optical
      potential.

PMID- 10060698
TI  - Subrecoil laser cooling with adiabatic transfer.

PMID- 10060699
TI  - Ionization of Rydberg wave packets by subpicosecond, half-cycle electromagnetic
      pulses.

PMID- 10060700
TI  - Vibrational dephasing mechanisms in hydrogen-bonded systems.

PMID- 10060701
TI  - Population pumping of excited vibrational states by spontaneous surface-enhanced
      Raman scattering.

PMID- 10060702
TI  - Resonant x-ray emission spectroscopy of molecular oxygen.

PMID- 10060703
TI  - Spontaneous generation of a longitudinal atomic density grating in sodium vapor.

PMID- 10060704
TI  - Differential cross-section representation from dispersion relations: A Regge Pole
      Approach.

PMID- 10060706
TI  - Photon chopping: New way to measure the quantum state of light.

PMID- 10060705
TI  - Selective measurements of pion transfer processes in alcohols and carboxylic
      acids using deuterated compounds.

PMID- 10060707
TI  - Observation of laser assisted photoelectric effect and femtosecond high order
      harmonic radiation.

PMID- 10060708
TI  - High-order harmonic generation in atom clusters.

PMID- 10060709
TI  - Ray splitting and quantum chaos.

PMID- 10060710
TI  - 3D Wire mesh photonic crystals.

PMID- 10060711
TI  - Resonant nonlinear dielectric response in a photonic band gap material.

PMID- 10060713
TI  - Composite power laws in shock fragmentation.

PMID- 10060712
TI  - Carrier wave shocking of femtosecond optical pulses.

PMID- 10060714
TI  - Magnetic field of a plasma wake driven by a laser pulse.

PMID- 10060715
TI  - Invariance of divertor retention on external particle flow in detached ASDEX
      upgrade discharges.

PMID- 10060716
TI  - Observed surface energy effects in confined diblock copolymers.

PMID- 10060717
TI  - Phason related stacking disorder in decagonal Al-Co-Ni.

PMID- 10060718
TI  - Nanomechanics of carbon tubes: Instabilities beyond linear response.

PMID- 10060719
TI  - Polyyne ring nucleus growth model for single-layer carbon nanotubes.

PMID- 10060720
TI  - Existence of electronic excitation enhanced crystallization in GeSb amorphous
      thin films upon ultrashort laser pulse irradiation.

PMID- 10060721
TI  - Self-diffusion coefficients in plastic crystals by multiple-pulse NMR in large
      static field gradients.

PMID- 10060722
TI  - Fluctuation-stabilized surface freezing of chain molecules.

PMID- 10060723
TI  - Diffusion of particles in free-standing liquid films.

PMID- 10060724
TI  - Island assisted surface alloying observed after Ni deposition on Au(110)-(1 x 2).

PMID- 10060725
TI  - Atomic view of the upward movement of step-edge and In-layer atoms of Ir
      surfaces.

PMID- 10060727
TI  - Plasmon-assisted electron emission from Al and Mg surfaces by slow ions.

PMID- 10060726
TI  - Intraband dynamics at the semiconductor band edge: Shortcomings of the Bloch
      equation method.

PMID- 10060728
TI  - Dynamic scaling of magnetic flux noise near the Kosterlitz-Thouless-Berezinskii
      transition in overdamped Josephson junction arrays.

PMID- 10060729
TI  - Vortex-lattice phase transitions in Bi2Sr2CaCu2 O8 crystals with different oxygen
      stoichiometry.

PMID- 10060730
TI  - Vortex pinning by competing disorder: Bose-glass to vortex-glass crossover.

PMID- 10060732
TI  - Enhancement of Bose-glass superconductivity in YBa2Cu3O7- delta thin films.

PMID- 10060731
TI  - Enhanced pinning with controlled splay configurations of columnar defects: rapid
      vortex motion at large angles.

PMID- 10060733
TI  - Long-range order versus random-singlet phases in quantum antiferromagnetic
      systems with quenched disorder.

PMID- 10060734
TI  - Observation of diamagnetic domains in beryllium by muon spin rotation
      spectroscopy.

PMID- 10060735
TI  - Singularities in optical spectra of quantum spin chains.

PMID- 10060736
TI  - Spin structure in magnetic multilayers with rough interfaces.

PMID- 10060737
TI  - Topological contributions to nonlinear elasticity in branched polymers.

PMID- 10060738
TI  - Similarity detection and localization.

PMID- 10060739
TI  - Collision of a field-driven polymer with a post: Electrophoresis in
      microlithographic arrays.

PMID- 10060740
TI  - Self-affine asperity model for earthquakes.

PMID- 10060741
TI  - Comment on "Role of hydrogen in C and Si(001) homoepitaxy"

PMID- 10060742
TI  - Ogitsu et al. reply.

PMID- 10060743
TI  - Semiclassical quantization using diffractive orbits.

PMID- 10060744
TI  - Spatiotemporal stochastic resonance in a phi4 model of kink-antikink nucleation.

PMID- 10060745
TI  - Monte Carlo renormalization of the 3D Ising model: Analyticity and convergence.

PMID- 10060746
TI  - Doppler peaks from active perturbations.

PMID- 10060747
TI  - Nucleon spin fluctuations and the supernova emission of neutrinos and axions.

PMID- 10060748
TI  - Weak interactions in supernova cores and saturation of nucleon spin fluctuations.

PMID- 10060750
TI  - New astrophysical constraints on the light-pseudoscalar-photon coupling.

PMID- 10060749
TI  - Signal for supernova nu micro and nu tau neutrinos in water C-caronerenkov
      detectors.

PMID- 10060752
TI  - Shell model Monte Carlo method for two-neutrino double beta decay.

PMID- 10060751
TI  - Tau decays into three charged leptons and two neutrinos.

PMID- 10060753
TI  - Circumstantial evidence for critical behavior in peripheral Au+Au collisions at
      35 MeV/nucleon.

PMID- 10060754
TI  - Wavelets in self-consistent electronic structure calculations.

PMID- 10060755
TI  - Ratio of cross sections for double to single ionization of He by 85-400 eV
      photons.

PMID- 10060756
TI  - Raman cooling of atoms in an optical dipole trap.

PMID- 10060757
TI  - Precision lifetime measurements in H2: Disagreement with theory.

PMID- 10060758
TI  - Global Franck-Condon breakdown resulting from Cooper minima.

PMID- 10060759
TI  - Bose-Einstein condensation in trapped atomic gases.

PMID- 10060760
TI  - Convergent close-coupling method: A "Complete scattering theory"?

PMID- 10060761
TI  - Supershells in metal clusters: Self-consistent calculations and their
      semiclassical interpretation.

PMID- 10060762
TI  - Direct observation of coherent medium response under the condition of two-photon
      excitation of krypton by femtosecond UV-laser pulses.

PMID- 10060764
TI  - Classical chaos as an environment for dissipation.

PMID- 10060763
TI  - Relationship between delayed and spatially extended dynamical systems.

PMID- 10060765
TI  - Two-mode laser power spectra.

PMID- 10060767
TI  - Long wavelength instability for uniform shear flow.

PMID- 10060766
TI  - Three dimensional bright spatial soliton collision and fusion in a saturable
      Nonlinear Medium.

PMID- 10060768
TI  - Anomalous scaling exponents of a white-advected passive scalar.

PMID- 10060769
TI  - Theory of hybrid contact discontinuities.

PMID- 10060770
TI  - Crossing intrinsic depolarizing resonances by varying a partial Siberian snake.

PMID- 10060772
TI  - Fusion heating in a deuterium-tritium tokamak plasma.

PMID- 10060771
TI  - Experimental demonstration of high efficiency electron cyclotron autoresonance
      acceleration.

PMID- 10060773
TI  - High genus periodic gyroid surfaces of nonpositive Gaussian curvature.

PMID- 10060775
TI  - Nature of the collapse transition for polymers.

PMID- 10060774
TI  - Slow dynamics of water molecules in supercooled states.

PMID- 10060776
TI  - Propagating and localized elementary excitations in decagonal quasicrystals.

PMID- 10060777
TI  - Elastic forces that do no work and the dynamics of fast cracks.

PMID- 10060778
TI  - Roughening transition in a one-dimensional growth process.

PMID- 10060779
TI  - Soluble infinite-range model of kinetic roughening.

PMID- 10060780
TI  - Scaling properties of the critical nucleus in classical and molecular-based
      theories of vapor-liquid nucleation.

PMID- 10060781
TI  - Free energy contributions to the hcp-bcc transformation in transition metals.

PMID- 10060782
TI  - Single-file diffusion observation.

PMID- 10060783
TI  - Observation of nonlinear propagation of spin-entropy wave in superfluid 3He.

PMID- 10060784
TI  - Nucleation in Si(001) homoepitaxial growth.

PMID- 10060785
TI  - Detection of compressible and incompressible states in quantum dots and antidots
      by far-infrared spectroscopy.

PMID- 10060787
TI  - Chiral surface states in the bulk quantum Hall effect.

PMID- 10060786
TI  - Experimental test of the quantum shot noise reduction theory.

PMID- 10060788
TI  - Drag in paired electron-hole layers.

PMID- 10060789
TI  - Vortex glass and lattice melting transitions in a YNi2B2C single crystal.

PMID- 10060790
TI  - Interaction of ultrasound with vortices in type-II superconductors.

PMID- 10060791
TI  - Upper limit of the Bose-glass transition in YBa2Cu3O7 at high density of columnar
      defects.

PMID- 10060792
TI  - Oxygen induced suppression of the surface magnetization of Gd(0001).

PMID- 10060793
TI  - Impurity NMR study of the acceptor band in Si(B).

PMID- 10060795
TI  - Stability and the fractal structure of a spherical flame in a self-similar
      regime.

PMID- 10060794
TI  - Reflectance difference spectroscopy: Experiment and theory for the model system
      Si(001):As and application to Si(001).

PMID- 10060796
TI  - Noncommuting mixed states cannot be broadcast.

PMID- 10060797
TI  - Comment on "Probing the nuclear liquid-gas phase transition"

PMID- 10060798
TI  - Pochodzalla et al. reply.

PMID- 10060799
TI  - Comment on "Screening in semiconductor nanocrystallites and its consequences for
      porous silicon"

PMID- 10060803
TI  - Impossibility of measuring the wave function of a single quantum system.

PMID- 10060802
TI  - Exactly solvable hierarchical optimization problem related to percolation.

PMID- 10060804
TI  - DNA molecular cousin of Schrodinger's cat: A curious example of quantum
      measurement.

PMID- 10060805
TI  - Test of the symmetrization postulate for spin-0 particles.

PMID- 10060806
TI  - Spectroscopic test of the symmetrization postulate for spin-0 nuclei.

PMID- 10060807
TI  - Nucleosynthesis and the mass of the tau neutrino.

PMID- 10060808
TI  - Search for the rare decay W+/---> pi +/-+ gamma.

PMID- 10060809
TI  - Long range potentials for two Na3p atoms including ionic-covalent interaction and
      fine structure: Application to two-color photoassociation spectroscopy.

PMID- 10060810
TI  - Precision lifetime measurements on NaI3p 2P1/2 and 3p 2P 3/2 by beam-gas-laser
      spectroscopy.

PMID- 10060811
TI  - High precision linewidth measurement of laser-cooled atoms: Resolution of the Na
      3p 2P3/2 lifetime discrepancy.

PMID- 10060812
TI  - Two-photon detachment of negative ions via magnetic dipole transitions.

PMID- 10060813
TI  - Nonstationary, nondispersive wave packets in a Rydberg atom.

PMID- 10060814
TI  - Anomalous spectroscopy of Li4- clusters.

PMID- 10060815
TI  - Ionization of hydrogen and hydrogenic ions by antiprotons.

PMID- 10060816
TI  - Experimental observation of laser control: Electronic branching in the
      photodissociation of Na2.

PMID- 10060817
TI  - Computation of the Arnol'd web for the hydrogen atom in crossed electric and
      magnetic fields.

PMID- 10060818
TI  - Wave-mixing and vector phase conjugation by polarization-dependent saturable
      absorption in Cr 4+:YAG.

PMID- 10060820
TI  - Interface pinning and the dynamics of capillary rise in porous media.

PMID- 10060819
TI  - Fusion rules in turbulent systems with flux equilibrium.

PMID- 10060821
TI  - Density fluctuations in an electrolyte from generalized Debye-Huckel theory.

PMID- 10060823
TI  - Random walks on bundled structures.

PMID- 10060822
TI  - Monte Carlo studies of helicity modulus and heat capacity of a coupled XY model
      in two dimensions.

PMID- 10060824
TI  - Exact solution of an octagonal random tiling model.

PMID- 10060826
TI  - Fundamental role of creation and activation in radiation-induced defect
      production in high-purity amorphous SiO2.

PMID- 10060825
TI  - 13C Magic-angle-spinning NMR study of the electronic properties of the AC60
      polymers (A=K,Rb,Cs).

PMID- 10060827
TI  - Phase transition in the Peierls model and the possibility of one-dimensional
      melting.

PMID- 10060828
TI  - New high-pressure phase of ice.

PMID- 10060830
TI  - Local vs average behavior on inhomogeneous structures: Recurrence on the average
      and a further extension of Mermin-Wagner theorem on graphs.

PMID- 10060829
TI  - One-dimensional disordered bosonic Hubbard model: A density-matrix
      renormalization group study.

PMID- 10060831
TI  - Nuclear magnetic ordering of 3He clusters in solid 4He.

PMID- 10060832
TI  - Initial process of Si homoepitaxial growth on Si(001).

PMID- 10060833
TI  - Adsorbate induced change of equilibrium surface during crystal growth: Si on
      Si(111)/H.

PMID- 10060834
TI  - Physical nature of critical wave functions in Fibonacci systems.

PMID- 10060835
TI  - Nature of luminescent surface states of semiconductor nanocrystallites.

PMID- 10060836
TI  - Enhanced binding energy of one-dimensional excitons in quantum wires.

PMID- 10060837
TI  - Fast and slow electrons in liquid neon.

PMID- 10060839
TI  - Particle-hole symmetry and the Bose glass to superfluid transition.

PMID- 10060838
TI  - Inverse Bloch oscillator: Strong terahertz-photocurrent resonances at the Bloch
      frequency.

PMID- 10060840
TI  - Effect of the coupling to a superconductor on the level statistics of a metal
      grain in a magnetic field.

PMID- 10060841
TI  - Metastable filamentary vortex flow in thin film superconductors.

PMID- 10060842
TI  - Nature of phase transitions of superconducting wire networks in a magnetic field.

PMID- 10060844
TI  - Evidence of in-plane superstructure formation in phase-separated and staged
      single crystal La2CuO4+ delta.

PMID- 10060843
TI  - Pinning strength dependence of mixed-state Hall effect in YBa2Cu3O7 crystals with
      columnar defects.

PMID- 10060845
TI  - Critical properties of random quantum Potts and clock models.

PMID- 10060846
TI  - Fine structure splitting in the optical spectra of single GaAs quantum dots.

PMID- 10060848
TI  - Strong coupling between diffusive and elastic instabilities in directional
      solidification.

PMID- 10060847
TI  - Extended Van Hove singularity in a noncuprate layered superconductor Sr2RuO4.

PMID- 10060849
TI  - Anomalous viscous loss in emulsions.

PMID- 10060851
TI  - Conditions for adaptation of an evolving population.

PMID- 10060850
TI  - On-line Gibbs learning.

PMID- 10060852
TI  - Large discrete transition in a single DNA molecule appears continuous in the
      ensemble.

PMID- 10060854
TI  - Comment on "Gaussian orthogonal ensemble statistics in a microwave stadium
      billiard with chaotic dynamics: Porter-Thomas distribution and algebraic decay of
      time correlations"

PMID- 10060853
TI  - Single cell motion in aggregates of embryonic cells.

PMID- 10060855
TI  - Alt et al. reply.

PMID- 10060856
TI  - Comment on "Size dependence of excitons in silicon nanocrystals"

PMID- 10060857
TI  - Hill and Whaley reply.

PMID- 10060858
TI  - Comment on "Tunneling in mesoscopic magnetic molecules"

PMID- 10060859
TI  - Politi et al. reply.

PMID- 10060863
TI  - Dynamical current redistribution and non-Gaussian 1/f noise.

PMID- 10060862
TI  - External fluctuations in front propagation.

PMID- 10060864
TI  - Sagnac interferometer for gravitational-wave detection.

PMID- 10060866
TI  - Test of the running of alpha s in tau decays.

PMID- 10060865
TI  - Measurement of 0.25-3.2 GeV antiprotons in the cosmic radiation.

PMID- 10060867
TI  - Limits on flavor changing neutral currents in D0 meson decays.

PMID- 10060868
TI  - Measurement of sigma B(W-->e nu ) and sigma B(Z0-->e+e-) in pp-bar collisions at
      sqrt s =1.8 TeV.

PMID- 10060869
TI  - Multiple interactions in two-photon collisions.

PMID- 10060870
TI  - Lifetime of quasiparticles in hot QED plasmas.

PMID- 10060871
TI  - Anomalous mesonic interactions near a chiral phase transition.

PMID- 10060872
TI  - Effects of non-nucleonic degrees of freedom in the D(p

PMID- 10060873
TI  - Many-body calculations of the electron affinity for Ca and Sr.

PMID- 10060874
TI  - Analysis of triply excited states of atoms in hyperspherical coordinates.

PMID- 10060875
TI  - Raman versus non-Raman behavior in resonant Auger spectra of HCl.

PMID- 10060876
TI  - Electronic stopping in a He-H2 mixture substantially exceeds Bragg's rule value.

PMID- 10060877
TI  - Inversion of quantum jumps in quantum optical systems under continuous
      observation.

PMID- 10060878
TI  - Nonlinear perturbation theory of the incompressible Richtmyer-Meshkov
      instability.

PMID- 10060879
TI  - Observation of nonlinear effects in Compton scattering.

PMID- 10060880
TI  - Collisionless breakdown of magnetic insulation in plasmas.

PMID- 10060881
TI  - XUV amplification in a recombining z-pinch plasma.

PMID- 10060882
TI  - Fast ion production by laser filamentation in laser-produced plasmas.

PMID- 10060883
TI  - Multiple-energy x-ray holography: Atomic images of hematite (Fe2O3).

PMID- 10060884
TI  - Evidence for the importance of interactions between active defects in glasses.

PMID- 10060886
TI  - New hydrodynamic mechanism for drop coarsening.

PMID- 10060885
TI  - L12-D022 competition in the pseudobinary (Pt, Rh)3V, Pt3(V, Ti), and (Pd, Rh)3V
      alloys: Phase stability and electronic structure.

PMID- 10060887
TI  - Generalized helimagnets between two and four dimensions.

PMID- 10060888
TI  - Monolayer spreading of polydimethylsiloxane oil on surfactant solutions.

PMID- 10060889
TI  - Interplay of stress, structure, and stoichiometry in Ge-covered Si(001).

PMID- 10060890
TI  - Single adatom exchange in surfactant-mediated epitaxial growth.

PMID- 10060891
TI  - Morphology transition and layer-by-layer growth of Rh(111).

PMID- 10060892
TI  - Density functional and density matrix method scaling linearly with the number of
      atoms.

PMID- 10060893
TI  - Observation of hidden Fermi surface nesting in a two dimensional conductor.

PMID- 10060895
TI  - Dynamical localization-delocalization transition in the infinite-dimensional
      Hubbard-Holstein model.

PMID- 10060894
TI  - Insulator-metal transition in the one- and two-dimensional Hubbard models.

PMID- 10060896
TI  - Competing instabilities and metastable states in (Nd,Sm)1/2Sr1/2MnO3.

PMID- 10060897
TI  - Thermodynamic and electron diffraction signatures of charge and spin ordering in
      La1- xCaxMnO3.

PMID- 10060899
TI  - Non-Gaussian transport measurements and the Einstein relation in amorphous
      silicon.

PMID- 10060898
TI  - Thermal transport in a Luttinger liquid.

PMID- 10060900
TI  - Imaging hot-electron emission from metal-oxide-semiconductor structures.

PMID- 10060901
TI  - Thermodynamics of quantum Hall ferromagnets.

PMID- 10060902
TI  - Spin polarization and magnetic circular dichroism in photoemission from the 2p
      core level of ferromagnetic Ni.

PMID- 10060903
TI  - Magnetic susceptibility of ideal spin 1/2 Heisenberg antiferromagnetic chain
      systems, Sr2CuO3 and SrCuO2.

PMID- 10060904
TI  - Giant magnetoresistance from an electron waveguide effect in cobalt-copper
      multilayers.

PMID- 10060905
TI  - Time domain study of 57Fe diffusion using nuclear forward scattering of
      synchrotron radiation.

PMID- 10060906
TI  - Transient linear birefringence in GaAs quantum wells: Magnetic field dependence
      of coherent exciton spin dynamics.

PMID- 10060907
TI  - Semiclassical Fourier transform for quantum computation.

PMID- 10060908
TI  - Comment on "Reduced system dynamics from the N-body Schrodinger equation"

PMID- 10060909
TI  - Comment on "Reduced system dynamics from the N-body Schrodinger equation"

PMID- 10060910
TI  - Comment on "Kinematic scaling and crossover to scale invariance in martensite
      growth"

PMID- 10060911
TI  - Rao and Sengupta reply.

PMID- 10060912
TI  - Comment on "Quasiparticle decay effects in the superconducting density of states:
      Evidence for d-wave pairing in the cuprates"

PMID- 10060913
TI  - Coffey and Coffey reply.

PMID- 10060919
TI  - From soliton equations to integrable cellular automata through a limiting
      procedure.

PMID- 10060921
TI  - Absence of open strings in a lattice-free simulation of cosmic string formation.

PMID- 10060920
TI  - Superparamagnetic clustering of data.

PMID- 10060922
TI  - Extracting Rb and Rc without flavor tagging.

PMID- 10060923
TI  - New type of beam size effect in the W boson production at micro+ micro-
      colliders.

PMID- 10060924
TI  - Electroweak corrections to the muon anomalous magnetic moment.

PMID- 10060925
TI  - Search for right-handed W bosons and heavy W' in pp-bar collisions at sqrt s=1.8
      TeV.

PMID- 10060926
TI  - Search for the weak decay of an H dibaryon.

PMID- 10060927
TI  - Observation of an intense quasicontinuum of superdeformed rotational transitions
      in 143Eu.

PMID- 10060928
TI  - Reversal of radiation reaction force and instability of the ground state of an
      atom located above the surface of an active medium.

PMID- 10060929
TI  - Collision energy dependence of molecular fusion and fragmentation in C60 ++ C60
      collisions.

PMID- 10060930
TI  - Observation of two-photon decay of Rydberg atoms in a driven cavity.

PMID- 10060931
TI  - Quantum dynamical tunneling suppression by a laser field.

PMID- 10060932
TI  - Universal diffusion near the golden chaos border.

PMID- 10060933
TI  - Can a single-pulse standing wave induce chaos in atomic motion?

PMID- 10060934
TI  - Period doubling and strange attractors in quantum wells.

PMID- 10060935
TI  - Nonlinear control of dynamical systems from time series.

PMID- 10060936
TI  - Control of patterns in spatiotemporal chaos in optics.

PMID- 10060938
TI  - One-dimensional modulational instability in a crossed-field gap.

PMID- 10060937
TI  - Turbulence of capillary waves.

PMID- 10060939
TI  - Ion acceleration and direct ion heating in three-component magnetic reconnection.

PMID- 10060940
TI  - Anomalous absorption and scattering of short-pulse high-intensity lasers in
      underdense plasmas.

PMID- 10060942
TI  - Covariant relativistic hydrodynamics of multispecies plasma and generalized Ohm's
      law.

PMID- 10060941
TI  - Phase-matched high-order difference-frequency mixing in plasmas.

PMID- 10060944
TI  - Theory of chain association versus liquid condensation.

PMID- 10060943
TI  - Mechanism for disorder on GaAs(001)-(2 x 4) surfaces.

PMID- 10060945
TI  - Scale covariance of the Wrinkling law of turbulent propagating interfaces.

PMID- 10060946
TI  - Observation of large momentum phononlike modes in glasses.

PMID- 10060947
TI  - Mechanism for global optimization of river networks from local erosion rules.

PMID- 10060948
TI  - Thermodynamics of fractal networks.

PMID- 10060949
TI  - Critical behavior of the sandpile model as a self-organized branching process.

PMID- 10060950
TI  - Diffusion of Sb in strained and relaxed Si and SiGe.

PMID- 10060951
TI  - Time of flight spectra and chaotic dynamics in predesorption of physisorbed
      molecules.

PMID- 10060952
TI  - Mechanism of poisoning the catalytic activity of Pd(100) by a sulfur adlayer.

PMID- 10060954
TI  - Time correlations in 1D quantum impurity problems.

PMID- 10060953
TI  - Linear and nonlinear optical characteristics of the Falicov-Kimball model.

PMID- 10060955
TI  - Spin-glass insulator state in (Tb-La)2/3Ca1/3MnO3 perovskite.

PMID- 10060956
TI  - "Fermi liquid" shell model approach to composite fermion excitation spectra in
      fractional quantum Hall states.

PMID- 10060957
TI  - Nonuniversal metallic behavior of superconducting wires.

PMID- 10060958
TI  - Generation of a population inversion between quantum states of a macroscopic
      variable.

PMID- 10060959
TI  - Moving glass phase of driven lattices.

PMID- 10060961
TI  - Continuous 3D freezing transition in layered superconductors.

PMID- 10060960
TI  - Determination of the local lattice distortions in the CuO2 plane of
      La1.85Sr0.15CuO4.

PMID- 10060962
TI  - Random matrix theory of a chaotic Andreev quantum dot.

PMID- 10060964
TI  - Periodicity of the spin structure observed in the optical response of CeBi single
      crystals.

PMID- 10060963
TI  - Oscillatory magnetic anisotropy and quantum well states in Cu/Co/Cu(100) films.

PMID- 10060965
TI  - Sub-poissonian photon-state generation by Stark-effect blockade of emissions in a
      semiconductor diode driven by a constant-voltage source.

PMID- 10060967
TI  - Diffusion-controlled reactions at polymer-polymer interfaces.

PMID- 10060966
TI  - Regular and chaotic transport in asymmetric periodic potentials: Inertia
      ratchets.

PMID- 10060968
TI  - Polymer reaction kinetics at interfaces.

PMID- 10060969
TI  - Model for the elasticity of compressed emulsions.

PMID- 10060970
TI  - Limitation on the amount of accessible information in a quantum channel.

PMID- 10060971
TI  - Rifts in spreading wax layers.

PMID- 10060973
TI  - Comment on "Microscopic origin of magnetic anisotropy in Au/Co/Au probed with x
      ray magnetic circular dichroism"

PMID- 10060972
TI  - Quasirandom spanning tree model for the early river network.

PMID- 10060976
TI  - Dynamic linear response theory for a nonextensive system based on the Tsallis
      prescription.

PMID- 10060977
TI  - Local flux of low-energy antiprotons from evaporating primordial black holes.

PMID- 10060978
TI  - Shock emission model for gamma-ray bursts.

PMID- 10060979
TI  - Gauge theory of supergravity based only on a self-dual spin connection.

PMID- 10060981
TI  - Simple supersymmetric solution to the strong CP problem.

PMID- 10060980
TI  - Solution to the strong CP problem: Supersymmetry with parity.

PMID- 10060982
TI  - Experimental signatures of low energy gauge-mediated supersymmetry breaking.

PMID- 10060983
TI  - Supersymmetric analysis and predictions based on the collider detector at
      Fermilab ee gamma gamma + missing energy event.

PMID- 10060984
TI  - Studies of xi (2230) in J/ psi radiative decays.

PMID- 10060986
TI  - Relative deformations of superdeformed bands in 131,132Ce.

PMID- 10060985
TI  - Limits on the production of direct protons in 200A GeV 32S+Au collisions.

PMID- 10060987
TI  - Supersymmetric multiphonon structure.

PMID- 10060988
TI  - Energy properties of alpha -cluster matter in a microscopic description.

PMID- 10060989
TI  - Magneto-optic trapping of 210Fr.

PMID- 10060991
TI  - Fractional Stark state selective electric field ionization of very high-n Rydberg
      states of molecules.

PMID- 10060990
TI  - Electric field ionization of high Rydberg states of Ar with sequences of
      identical pulses.

PMID- 10060992
TI  - Resonant mechanisms in the vibrational excitation of ground state O2.

PMID- 10060993
TI  - Oscillations in the photoionization cross section of C60.

PMID- 10060994
TI  - Electromagnetic radiation by a tunneling charge.

PMID- 10060995
TI  - Laser-generated cavitation in absorbing liquid induced by acoustic diffraction.

PMID- 10060996
TI  - Measurement of dielectric suppression of bremsstrahlung.

PMID- 10060997
TI  - Pair correlation function and nonlinear kinetic equation for a spatially uniform
      polarizable nonideal plasma.

PMID- 10060999
TI  - Electron vortices produced by ultraintense laser pulses.

PMID- 10060998
TI  - Bursty wave instabilities in open driven plasmas.

PMID- 10061000
TI  - Temporal and spatial measurements of the electron density perturbation produced
      in the wake of an ultrashort laser pulse.

PMID- 10061001
TI  - Laser wakefield excitation and measurement by femtosecond longitudinal
      interferometry.

PMID- 10061002
TI  - Measurement of 0.35 microm laser imprint in a thin Si foil using an x-ray laser
      backlighter.

PMID- 10061003
TI  - Plasma-based inverse free-electron laser for high-gradient acceleration of
      electrons.

PMID- 10061004
TI  - Cellular structures in catalytic reactions with global coupling.

PMID- 10061005
TI  - Fluctuation-induced anisotropic pattern relaxation in critical polymer blends.

PMID- 10061006
TI  - Ab initio molecular dynamics simulations for collision between C60 - and alkali
      metal ions: A possibility of Li@C60.

PMID- 10061007
TI  - Cleavage anisotropy in tungsten single crystals.

PMID- 10061008
TI  - Quantum breathers in a nonlinear lattice.

PMID- 10061009
TI  - A theory of premelting dynamics for all power law forces.

PMID- 10061010
TI  - Adequacy of the Lifshitz theory for certain thin adsorbed films.

PMID- 10061011
TI  - The Sham-Schluter equation in time-dependent density-functional theory.

PMID- 10061012
TI  - Localization in highly anisotropic systems.

PMID- 10061013
TI  - Stark-cyclotron resonance in a semiconductor superlattice.

PMID- 10061015
TI  - Charge accumulation at InAs surfaces.

PMID- 10061014
TI  - Time resolved spectroscopy of single quantum dots: Fermi gas of excitons?

PMID- 10061016
TI  - Even denominator filling factors in the thermoelectric power of a two-dimensional
      electron gas.

PMID- 10061017
TI  - Boundary effects and the order parameter symmetry of high-Tc superconductors.

PMID- 10061018
TI  - NMR evidence for 1D antiferromagnetic properties in Cs1C60 and Rb1C60 polymers.

PMID- 10061019
TI  - Coulomb-induced suppression of band-edge singularities in the optical spectra of
      realistic quantum-wire structures.

PMID- 10061020
TI  - Colloidal flocculation in near-critical binary mixtures.

PMID- 10061022
TI  - Comment on "Levinson's theorem for the dirac equation"

PMID- 10061021
TI  - Melting of phospholipid tubules.

PMID- 10061024
TI  - Comment on "Collective dynamics in water by high energy resolution inelastic x
      ray scattering"

PMID- 10061023
TI  - Poliatzky replies.

PMID- 10061025
TI  - Sette et al. reply.

PMID- 10061026
TI  - Comment on "In-plane lattice reconstruction of Cu(001)"

PMID- 10061027
TI  - Comment on "In-plane lattice reconstruction of Cu(100)"

PMID- 10061028
TI  - Muller et al. reply.

PMID- 10061031
TI  - Quantum phase of a Bose-Einstein condensate with an arbitrary number of atoms.

PMID- 10061032
TI  - Fractional exclusion statistics and two dimensional electron systems.

PMID- 10061033
TI  - Partition function zeros of the square lattice Potts model.

PMID- 10061034
TI  - Directed compact lattice animals, restricted partitions of an integer, and the
      infinite-state Potts model.

PMID- 10061035
TI  - A measurement of the shape of the solar disk: The solar quadrupole moment, the
      solar octopole moment, and the advance of perihelion of the planet Mercury.

PMID- 10061036
TI  - Nonperturbative effects on nucleation.

PMID- 10061038
TI  - An attempt to construct the standard model with monopoles.

PMID- 10061037
TI  - Compositeness condition at the next-to-leading order in the Nambu-Jona-Lasinio
      model.

PMID- 10061039
TI  - Relative J/ psi to psi ' suppression in proton-nucleus and nucleus-nucleus
      collisions.

PMID- 10061040
TI  - Suppression of psi ' and J/ psi in high-energy heavy-ion collisions.

PMID- 10061041
TI  - Improved limit on the branching ratio of micro-->e conversion on lead.

PMID- 10061043
TI  - Spin-dependent orientation propensities revealed in polarized-electron-polarized
      photon coincidence studies.

PMID- 10061042
TI  - Two-electron Lamb-shift calculations on heliumlike ions.

PMID- 10061044
TI  - Electronic structure of small titanium clusters: Emergence and evolution of the
      3d band.

PMID- 10061045
TI  - Many-dimensional quantum energy flow at low energy.

PMID- 10061046
TI  - Fast pulsing and chaotic itinerancy with a drift in the coherence collapse of
      semiconductor lasers.

PMID- 10061047
TI  - Turbulent thermal diffusion of small inertial particles.

PMID- 10061048
TI  - Ratcheting motion of concentric rings in cellular flames.

PMID- 10061049
TI  - Novel x-ray source using rear side x-ray emission from the foil target.

PMID- 10061050
TI  - Luminosity-limiting coherent phenomena in electron-positron colliders.

PMID- 10061051
TI  - Ferroelectric order in model discotic nematic liquid crystals.

PMID- 10061053
TI  - Scaling of island distributions, percolation, and criticality in contour cuts
      through wrinkled surfaces.

PMID- 10061052
TI  - Molecular origin of friction in liquids.

PMID- 10061054
TI  - Complex fractal dimensions describe the hierarchical structure of diffusion
      limited-aggregate clusters.

PMID- 10061055
TI  - Computer simulation study of the melting transition in two dimensions.

PMID- 10061056
TI  - Surface region of superfluid helium as an inhomogeneous Bose-condensed gas.

PMID- 10061057
TI  - First observation of (100) and (211) facets on 3He crystals.

PMID- 10061058
TI  - Coupled-barrier diffusion: The case of oxygen in silicon.

PMID- 10061059
TI  - Numerical renormalization-group study of particle-hole symmetry breaking in two
      channel Kondo problem: Effect of repulsion among conduction electrons and
      potential scattering.

PMID- 10061060
TI  - Particle-hole asymmetry in the two-impurity Kondo model.

PMID- 10061061
TI  - Heavy quasiparticles in the Anderson lattice model.

PMID- 10061063
TI  - Integrability and coherence of hopping between 1D correlated electron systems.

PMID- 10061062
TI  - Anomalous magnetic properties of metallic V2O3 under pressure.

PMID- 10061064
TI  - Interacting electrons in disordered potentials: Conductance versus persistent
      currents.

PMID- 10061065
TI  - Effect of pressure on the magnetoresistance of single crystal
      Nd0.5Sr0.36Pb0.14MnO3- delta.

PMID- 10061066
TI  - Evidence for the formation of unoccupied states in poly(2,3-diphenylphenylene
      vinylene) following the deposition of metal.

PMID- 10061067
TI  - Near-band-edge photoluminescence from pseudomorphic Si1-yCy/Si quantum well
      structures.

PMID- 10061068
TI  - Gap anisotropy in the layered high temperature superconductors.

PMID- 10061069
TI  - Inelastic light scattering from magnetic fluctuations in CuGeO3.

PMID- 10061070
TI  - Photonic band structure of fcc colloidal crystals.

PMID- 10061071
TI  - Origin of traveling rolls in electroconvection of nematic liquid crystals.

PMID- 10061072
TI  - New algorithm for protein design.

PMID- 10061073
TI  - Neuron adhesion on a silicon chip probed by an array of field-effect transistors.

PMID- 10061074
TI  - Comment on "Limits on Dark Matter Using Ancient Mica"

PMID- 10061075
TI  - Snowden-Ifft, Freeman, and Price Reply.

PMID- 10061076
TI  - Comment on "Restricted Diffusion of the Conduction Electrons in Quasi-One
      Dimensional Organic Conductors"

PMID- 10061077
TI  - Dormann and Kaplan Reply.

PMID- 10061078
TI  - Gravitational breaking of the grand unified theory group and the grand unified
      theory-Planck hierarchy.

PMID- 10061079
TI  - Asymmetries for elastic scattering of pi + from polarized 3He and the Delta 
      neutron spin-spin interaction.

PMID- 10061080
TI  - Energy staggering in superdeformed bands in 131Ce, 132Ce, and 133Ce.

PMID- 10061081
TI  - Strong hyperfine induced quenching of a metastable state in Xe+ observed by
      hyperfine selective laser probing of a stored ion beam.

PMID- 10061082
TI  - State-selective electron capture in low velocity multiply charged ion, helium
      collisions.

PMID- 10061083
TI  - Measurement induced localization from spontaneous decay.

PMID- 10061084
TI  - Index of refraction for an optical medium with clamped quantum phase.

PMID- 10061085
TI  - Role of the environment in chaotic quantum dynamics.

PMID- 10061086
TI  - Doppler shift of self-reflected optical pulses at an interface: Dynamic nonlinear
      optical skin effect.

PMID- 10061087
TI  - Observation of Manakov spatial solitons in AlGaAs planar waveguides.

PMID- 10061088
TI  - Nonequilibrium brittle fracture propagation: Steady state, oscillations, and
      intermittency.

PMID- 10061090
TI  - Scalings and relative scalings in the Navier-Stokes turbulence.

PMID- 10061089
TI  - Nonuniversality of the scaling exponents of a passive scalar convected by a
      random flow.

PMID- 10061091
TI  - Plasma suppression of beam-beam interaction in circular colliders.

PMID- 10061092
TI  - Reduction of proton losses in HERA by compensating tune ripple due to power
      supplies.

PMID- 10061093
TI  - Demonstration of emittance compensation through the measurement of the slice
      emittance of a 10-ps electron bunch.

PMID- 10061094
TI  - Location of ion-acoustic waves from back and side stimulated Brillouin
      scattering.

PMID- 10061095
TI  - New phase-sensitive method of single-crystal characterization under x-ray
      diffraction conditions.

PMID- 10061096
TI  - Investigation of the phase shift in x-ray forward diffraction using an x-ray
      interferometer.

PMID- 10061097
TI  - Lyapunov spectra, instantaneous normal mode spectra, and relaxation in the
      Lennard-Jones liquid.

PMID- 10061099
TI  - Nucleation initiated spinodal decomposition in a polymerizing system.

PMID- 10061098
TI  - Fluid mixtures of parallel hard cubes.

PMID- 10061100
TI  - Invasion percolation and global optimization.

PMID- 10061101
TI  - Invasion percolation and Eden growth: Geometry and universality.

PMID- 10061102
TI  - Transverse force on a quantized vortex in a superfluid.

PMID- 10061103
TI  - Evidence for convective effects in breath figure formation on volatile fluid
      surfaces.

PMID- 10061104
TI  - Simulating the spreading of a drop in the terraced wetting regime.

PMID- 10061105
TI  - Formation of condensed phase patterns in adsorption layers.

PMID- 10061106
TI  - Noise-induced roughening evolution of amorphous Si films grown by thermal
      evaporation.

PMID- 10061108
TI  - New model of the initial stages of Si(111)-(7 x 7) oxidation.

PMID- 10061107
TI  - Dimensionally induced structural transformations in titanium-aluminum
      multilayers.

PMID- 10061109
TI  - Quantum oscillations in the layered perovskite superconductor Sr2RuO4.

PMID- 10061110
TI  - Diffusion and charge dynamics of negatively charged muonium in n-type GaAs.

PMID- 10061112
TI  - Photorefractive Gunn effect.

PMID- 10061111
TI  - Quantum localization effects on spin transport in semiconductor quantum wells
      with zinc-blende crystal structure.

PMID- 10061113
TI  - Direct measurement of the band structure of a one-dimensional surface
      superlattice.

PMID- 10061114
TI  - Observation of hot-electron shot noise in a netallic resistor.

PMID- 10061116
TI  - Supercurrent noise in quantum point contacts.

PMID- 10061115
TI  - Measurement of the far-infrared magnetoconductivity tensor of superconducting
      YBa2Cu3O7- delta thin films.

PMID- 10061117
TI  - Current-loop model for the intermediate state of type-I superconductors.

PMID- 10061118
TI  - Phase diagram of depleted Heisenberg model for CaV4O9.

PMID- 10061119
TI  - Lattice effects and magnetic order in the canted ferromagnetic insulator
      La0.875>Sr0.125MnO 3+ delta.

PMID- 10061120
TI  - Macroscopic measurement of resonant magnetization tunneling in high-spin
      molecules.

PMID- 10061121
TI  - New type of oscillatory exchange coupling induced by ordering in the magnetic
      layers.

PMID- 10061123
TI  - Sonoluminescence as quantum vacuum radiation.

PMID- 10061122
TI  - Direct observation of the spin-density-wave gap in (TMTSF)2PF 6.

PMID- 10061124
TI  - Enhanced resonant x-ray emissions of mechanically milled hexagonal boron nitride
      in boron K-shell excitation.

PMID- 10061125
TI  - Resonant coherent excitation of surface channeled ions.

PMID- 10061126
TI  - Dense and sparse vortices in excitable media drift in opposite directions in
      electric field.

PMID- 10061127
TI  - Simultaneous action of electric fields and nonelectric forces on a
      polyelectrolyte: Motion and deformation.

PMID- 10061128
TI  - Melting of metastable crystallites in charge-stabilized colloidal suspensions.

PMID- 10061130
TI  - Collective motion in a system of motile elements.

PMID- 10061129
TI  - Extremely dilute lyotropic 3D crystalline phase in a
      water/oil/surfactant/cosurfactant mixture.

PMID- 10061131
TI  - Comment on "Universal scaling functions in critical phenomena"

PMID- 10061133
TI  - Comment on "Brown dwarfs, quark stars, and quark-hadron phase transition"

PMID- 10061132
TI  - Hu replies.

PMID- 10061134
TI  - Cottingham, Kalafatis, and Vinh Mau reply.

PMID- 10061135
TI  - Comment on the origin of the high energy diffuse gamma -ray background.

PMID- 10061136
TI  - Dar and Shaviv reply.

PMID- 10061138
TI  - Dispersion velocity of galactic dark matter particles.

PMID- 10061137
TI  - Entropy of the K-satisfiability problem.

PMID- 10061139
TI  - Massless string theory black holes as black diholes and quadruholes.

PMID- 10061140
TI  - Electromagnetic splittings and light quark masses in lattice QCD.

PMID- 10061142
TI  - Matter radii of light halo nuclei.

PMID- 10061141
TI  - Measurement of the form factors for B-bar0-->D*+

PMID- 10061143
TI  - Strangelet search in Pb-Pb interactions at 158 GeV/c per nucleon.

PMID- 10061144
TI  - In-plane retardation of collective expansion in Au+Au collisions.

PMID- 10061145
TI  - High resolution measurements of partial photoionization cross sections in hollow
      lithium: A critical comparison with advanced many-body calculations.

PMID- 10061146
TI  - Photoelectron soft x-ray fluorescence coincidence spectroscopy on free molecules.

PMID- 10061147
TI  - Spin polarized Auger electrons: The Xe M4,5N4,5N4,5 case.

PMID- 10061148
TI  - Creating and probing electronic wave packets using half-cycle pulses.

PMID- 10061149
TI  - Fluorescence of oriented molecules in a microcavity.

PMID- 10061150
TI  - Experimental demonstration of enhanced index of refraction via quantum coherence
      in Rb.

PMID- 10061151
TI  - Is there a unique operator for the phase difference of two quantum fields?

PMID- 10061152
TI  - Response of a two-level system driven by two strong fields.

PMID- 10061153
TI  - Quantum chaos, irreversible classical dynamics, and random matrix theory.

PMID- 10061154
TI  - Generic behavior of grazing impact oscillators.

PMID- 10061155
TI  - Optical solitons in presence of Kerr dispersion and self-frequency shift.

PMID- 10061156
TI  - Dissipative solitary states in driven surface waves.

PMID- 10061157
TI  - Scaling behavior in turbulence is doubly anomalous.

PMID- 10061159
TI  - Chaotic transport in time-dependent symplectic maps.

PMID- 10061158
TI  - Prediction of turbulent velocity profile in couette and poiseuille flows from
      first principles.

PMID- 10061160
TI  - Relativistic magnetic self-channeling of light in near-critical plasma: Three
      dimensional particle-in-cell simulation.

PMID- 10061161
TI  - Low energy off-axis holography in electron microscopy.

PMID- 10061162
TI  - 14N nuclear quadrupole dips in the proton spin-lattice relaxation dispersion in
      the smectic-C phase of HpAB.

PMID- 10061163
TI  - Is heteropolymer freezing well described by the random energy model?

PMID- 10061164
TI  - Landau-Ginzburg theory of self-organized criticality.

PMID- 10061165
TI  - Dynamics of rough Ge(001) surfaces at low temperatures.

PMID- 10061166
TI  - Epitaxial growth of Omega-Titanium on the (111) surface of Alpha-Iron.

PMID- 10061167
TI  - Diffusive spreading of chainlike molecules on surfaces.

PMID- 10061168
TI  - 1D generalized statistics gas: A gauge theory approach.

PMID- 10061170
TI  - Effects of electron-electron interactions on the integer quantum Hall
      transitions.

PMID- 10061169
TI  - Strongly driven quantum wells: An analytical solution to the time-dependent
      Schrodinger equation.

PMID- 10061171
TI  - Thermodynamics and spin polarizations of the fractional quantum Hall states.

PMID- 10061172
TI  - Vortex dynamics in two-dimensional Amorphous Mo77Ge23 films.

PMID- 10061173
TI  - ac long-range phase-coherent effects in mesoscopic superconductor-normal metal
      structures.

PMID- 10061174
TI  - Universality of flux creep in superconductors with arbitrary shape and current
      voltage law.

PMID- 10061175
TI  - Coincidence of vortex-lattice melting and loss of vortex correlation along the c
      direction in untwinned YBa2 Cu3O7- delta single crystals.

PMID- 10061176
TI  - Phase diagram of S=1 bond-alternating XXZ chains.

PMID- 10061177
TI  - Commensurate to incommensurate charge ordering and its real space images in
      La0.5Ca0.5MnO3.

PMID- 10061178
TI  - Unconventional ferromagnetic transition in La1-xCaxMnO3.

PMID- 10061179
TI  - Density matrix renormalization group applied to the ground state of the XY spin
      Peierls system.

PMID- 10061180
TI  - Resonant inelastic x-ray scattering in hexagonal boron nitride observed by soft-x
      ray fluorescence spectroscopy.

PMID- 10061181
TI  - Fractal formation and ordering in random sequential adsorption.

PMID- 10061183
TI  - Probing potential-tuned resonant tunneling through redox molecules with scanning
      tunneling microscopy.

PMID- 10061182
TI  - Fingerlike aggregates in thin-layer electrodeposition.

PMID- 10061184
TI  - Criterion that determines the foldability of proteins.

PMID- 10061186
TI  - Buckling microtubules in vesicles.

PMID- 10061185
TI  - Subthreshold dynamics in periodically stimulated squid giant axons.

PMID- 10061187
TI  - Multifractal structure of auroral electrojet index data.

PMID- 10061189
TI  - Comment on "Quantum backreaction on 'Classical' variables."

PMID- 10061188
TI  - Comment on "Statistical mechanics of non-abelian Chern-Simons particles"

PMID- 10061190
TI  - Comment on "Quantum backreaction on 'Classical' variables."

PMID- 10061191
TI  - Can classical and quantum variables have a consistent mutual interaction?

PMID- 10061192
TI  - Anderson replies.

PMID- 10061193
TI  - Comment on "Direct observation of transition from delayed ionization to direct
      ionization for free C60 and C70: thermionic emission?"

PMID- 10061194
TI  - Stuke and Zhang reply.

PMID- 10061195
TI  - Comment on "Nature of crossover between ising-like and mean-field critical
      behavior in fluids and fluid mixtures"

PMID- 10061196
TI  - Anisimov et al. reply.

PMID- 10061197
TI  - Comment on "Anomalous tracer diffusion on surfaces"

PMID- 10061202
TI  - Novel correlations in two dimensions: Some exact solutions.

PMID- 10061203
TI  - Nonperturbative renormalization group equation and beta function in N=2
      supersymmetric Yang-Mills theory.

PMID- 10061204
TI  - Detecting light-gluino-containing hadrons.

PMID- 10061205
TI  - Signatures for squarks in the light gaugino scenario.

PMID- 10061207
TI  - Two-loop QCD corrections to b-->c transitions at zero recoil.

PMID- 10061208
TI  - Color-octet contributions to J/ psi photoproduction.

PMID- 10061206
TI  - First observation of the decay tau --->K- eta nu tau.

PMID- 10061209
TI  - Unified description of collective bands of even-even nuclei and fingerprint of
      the nuclear gamma shape.

PMID- 10061210
TI  - Ultrashort-lived non-Rydberg doubly excited resonances observed in molecular
      photoionization.

PMID- 10061211
TI  - Observation of enhanced ionization of molecular ions in intense laser fields.

PMID- 10061213
TI  - Phase measurement by projection synthesis.

PMID- 10061212
TI  - Induced emission due to the quantized motion of ultracold atoms passing through a
      micromaser cavity.

PMID- 10061214
TI  - Stokes phenomenon in chaotic systems: Pruning trees of complex paths with
      principle of exponential dominance.

PMID- 10061216
TI  - Observation of nondegenerate photorefractive parametric amplification.

PMID- 10061215
TI  - New method for computing topological pressure.

PMID- 10061217
TI  - Observation of stimulated transition radiation.

PMID- 10061218
TI  - Lagrangian formalism for the Rayleigh-Taylor instability.

PMID- 10061219
TI  - Observation of controlled intermittent chaos in ion-beam-plasma instabilities.

PMID- 10061220
TI  - Atomic-scale observations of alloying at the Cr-Fe(001) interface.

PMID- 10061221
TI  - Scanning tunneling spectroscopy of one-dimensional surface states on a metal
      surface.

PMID- 10061222
TI  - Island of vapor-liquid coexistence in dipolar hard-core systems.

PMID- 10061223
TI  - Facet growth of 4He crystals at mK temperatures.

PMID- 10061224
TI  - Networks of steps on crystal surfaces.

PMID- 10061226
TI  - Collective effects of excitons in multiple-quantum-well Bragg and anti-Bragg
      structures.

PMID- 10061225
TI  - Correlated jump-exchange processes in the diffusion of Ag on Ag(110).

PMID- 10061227
TI  - Order-N Green's function technique for local environment effects in alloys.

PMID- 10061228
TI  - Disordered electrons in a strong magnetic field: Transfer matrix approaches to
      the statistics of the local density of states.

PMID- 10061229
TI  - Inelastic x-ray scattering study of the metal-antiferromagnetic insulator
      transition in V2O3.

PMID- 10061230
TI  - Electronic aspects of the ferromagnetic transition in manganese perovskites.

PMID- 10061231
TI  - Fermi edge singularities in doped quantum wells with strong in-plane type I
      modulation.

PMID- 10061232
TI  - Finite size analysis of Luttinger liquids with a source of 2k f scattering.

PMID- 10061233
TI  - Quantized Hall effect in ultrathin metallic films.

PMID- 10061234
TI  - Enhancement of the tunneling density of states in Tomonaga-Luttinger liquids.

PMID- 10061235
TI  - Resonance-assisted hot electron femtochemistry at surfaces.

PMID- 10061236
TI  - Spin gap in HgBa2Ca2Cu3O8+ delta single crystals from 63Cu NMR.

PMID- 10061237
TI  - Exact solution and spectral flow for twisted Haldane-Shastry model.

PMID- 10061239
TI  - Ultrafast spin dynamics in ferromagnetic nickel.

PMID- 10061238
TI  - Magnetic susceptibility of insulators from first principles.

PMID- 10061240
TI  - Interlayer exchange coupling: The effect of substitutional disorder.

PMID- 10061241
TI  - Nuclear resonance energy analysis of inelastic x-ray scattering.

PMID- 10061243
TI  - Valence-band dispersion in angle-resolved resonant photoemission from LaSb.

PMID- 10061242
TI  - Positron quantum reflection in thin metal films and efficient generation of high
      brightness low energy positron beams at 4.2 K.

PMID- 10061244
TI  - Shear induced displacement of the spinodal of Brownian systems.

PMID- 10061245
TI  - Experimental observation of coherent millimeter wave radiation in a folded
      waveguide employed with a gyrating electron beam.

PMID- 10061246
TI  - Biasing Brownian motion in different directions in a 3-state fluctuating
      potential and an application for the separation of small particles.

PMID- 10061247
TI  - Quantum bit regeneration.

PMID- 10061248
TI  - Dynamics of a traveling density wave model for earthquakes.

PMID- 10061249
TI  - Comment on "Electronic model for superconductivity"

PMID- 10061250
TI  - Essler, Korepin, and Schoutens reply.

PMID- 10061252
TI  - Kolosov replies.

PMID- 10061251
TI  - Comment on "Nanoscale visualization and control of ferroelectric domains by
      atomic force microscopy"

PMID- 10061254
TI  - Quantum phase in interferometry.

PMID- 10061255
TI  - Dynamical entropies applied to stochastic resonance.

PMID- 10061256
TI  - Cauchy-characteristic matching: A new approach to radiation boundary conditions.

PMID- 10061257
TI  - Search for chargino-neutralino production in pp-bar collisons at sqrt s=1.8 TeV.

PMID- 10061259
TI  - Collective T- and P-odd electromagnetic moments in nuclei with octupole
      deformations.

PMID- 10061258
TI  - First evidence for the decay KL-->e+e- micro+ micro-

PMID- 10061260
TI  - Final ion-charge resolving electron spectroscopy: Photoionization studies on Sm
      and Eu.

PMID- 10061261
TI  - Double ionization of He by fast protons at large energy transfer.

PMID- 10061263
TI  - Spin configuration of Gd13 clusters.

PMID- 10061262
TI  - Absolute electron-impact ionization cross section measurements using a magneto
      optical trap.

PMID- 10061264
TI  - Numerical evidence of an embryonic orientational phase transition in small
      nitrogen clusters.

PMID- 10061265
TI  - Zeno effect in parametric down-conversion.

PMID- 10061266
TI  - Direct probing of quantum phase space by photon counting.

PMID- 10061267
TI  - Strange nonattracting chaotic sets, crises, and fluctuating Lyapunov exponents.

PMID- 10061269
TI  - Small beam nonparaxiality arrests self-focusing of optical beams.

PMID- 10061268
TI  - Origin of power-law spatial correlations in distributed oscillators and maps with
      nonlocal coupling.

PMID- 10061270
TI  - Test-particle transport in strong electrostatic drift turbulence with finite
      Larmor radius effects.

PMID- 10061271
TI  - Theory of high-mode phenomena for stellarators.

PMID- 10061272
TI  - Dimensional crossover in the phase separation kinetics of thin polymer blend
      films.

PMID- 10061273
TI  - Anomalous diffusion properties of wave packets on quasiperiodic chains.

PMID- 10061274
TI  - Phase structure of systems with multiplicative noise.

PMID- 10061275
TI  - Tricritical and critical end-point phenomena under random bonds.

PMID- 10061276
TI  - Pressure-induced structural transformations in Si nanocrystals: Surface and shape
      effects.

PMID- 10061277
TI  - Wall tension and heterogeneous substrate.

PMID- 10061278
TI  - Femtosecond infrared emission resulting from coherent charge oscillations in
      quantum wells.

PMID- 10061280
TI  - Quantum Monte Carlo evidence for superconductivity in the three-band hubbard
      Model in Two Dimensions.

PMID- 10061279
TI  - Anomalous flux quantization in a hubbard ring with correlated hopping.

PMID- 10061281
TI  - Berry's phase and a possible new topological current drive in certain weak link
      superconducting systems.

PMID- 10061282
TI  - Quantum-limited electrometer based on single cooper pair tunneling.

PMID- 10061283
TI  - Multicritical crossovers near the dilute bose gas quantum critical point.

PMID- 10061284
TI  - Isotropic spin-wave theory of short-range magnetic order.

PMID- 10061285
TI  - Noncollinear intra-atomic magnetism.

PMID- 10061286
TI  - Isolated spin pairs and two dimensional magnetism in SrCr9pGa12-9pO19.

PMID- 10061287
TI  - Surfactant-mediated modification of the magnetic properties of Co/Cu(111) thin
      films and superlattices.

PMID- 10061288
TI  - "Tuliplike" scattering patterns in wormlike micelles under shear flow.

PMID- 10061289
TI  - Nontopological saddle-splay and curvature instabilities from anisotropic membrane
      inclusions.

PMID- 10061290
TI  - RNA virus evolution via a fitness-space model.

PMID- 10061291
TI  - Shape deformation and phase separation dynamics of two-component vesicles.

PMID- 10061292
TI  - Comment on "Large-scale molecular dynamics study of entangled hard-chain fluids"

PMID- 10061293
TI  - Smith, Hall, and Freeman Reply.

PMID- 10061295
TI  - Radzihovsky Replies.

PMID- 10061294
TI  - Comment on "Theory of continuous Hc2 normal-to-superconducting transition"

PMID- 10061296
TI  - Zero-dispersion nonlinear resonance in dissipative systems.

PMID- 10061297
TI  - Higgsino cold dark matter motivated by collider data.

PMID- 10061299
TI  - Determining the CP nature of a neutral Higgs boson at the CERN large hadron
      collider.

PMID- 10061300
TI  - Random matrix model of QCD at finite density and the nature of the quenched
      limit.

PMID- 10061298
TI  - Measurements of the B- and B-bar0 meson lifetimes using semileptonic decays.

PMID- 10061301
TI  - Effects from changes in the final state spectrum on the neutrino mass
      determination from T2 beta decay experiments.

PMID- 10061302
TI  - Lifetime measurements of superdeformed bands in 148-149Gd and 152Dy: Evidence for
      structure-dependent elongations.

PMID- 10061303
TI  - Microscopic simulations of gamma cascades in warm rotating nuclei.

PMID- 10061304
TI  - Spin decomposition of the Delta resonance cross section using the 12C(p

PMID- 10061306
TI  - First angle-resolved photoelectron measurements following inner-shell resonant
      excitation in a singly charged ion.

PMID- 10061305
TI  - Isospin dependence of collective flow in heavy-ion collisions at intermediate
      energies.

PMID- 10061307
TI  - Laser spectroscopy of atoms guided by evanescent waves in micron-sized hollow
      optical fibers.

PMID- 10061308
TI  - Atomic Landau-Zener tunneling and Wannier-Stark ladders in optical potentials.

PMID- 10061310
TI  - Observation of atomic Wannier-Stark ladders in an accelerating optical potential.

PMID- 10061309
TI  - Bloch oscillations of atoms in an optical potential.

PMID- 10061311
TI  - Hyperfine-induced lifting of parity degeneracy in noninverting molecules.

PMID- 10061312
TI  - Quantum nondemolition measurement of the motional energy of a trapped atom.

PMID- 10061313
TI  - Kolmogorov and nonstationary spectra of optical turbulence.

PMID- 10061314
TI  - Diffusing light photography of fully developed isotropic ripple turbulence.

PMID- 10061315
TI  - Direct observation of beam bunching produced by a high power microwave free
      electron laser.

PMID- 10061317
TI  - Formation of duct and self-focusing in plasma by high power microwave.

PMID- 10061316
TI  - Experimental comparison of classical versus ablative Rayleigh-Taylor instability.

PMID- 10061318
TI  - Spectroscopic evidence for large ( >> 1 microm) lithium-colloid creation in
      electron-irradiated Li2O single crystals.

PMID- 10061319
TI  - Dynamic exponent of the two-dimensional Ising model and Monte Carlo computation
      of the subdominant eigenvalue of the stochastic matrix.

PMID- 10061320
TI  - Freezing between two and three dimensions.

PMID- 10061321
TI  - Scaling of 6n-fold bond-orientational order parameters in a hexatic liquid
      crystal thin film.

PMID- 10061322
TI  - Direct spectroscopic observation of elementary excitations in superfluid He
      droplets.

PMID- 10061323
TI  - Scaling of self-avoiding tethered membranes: 2-loop renormalization group
      results.

PMID- 10061325
TI  - Crystallization of the one-component plasma at finite temperature.

PMID- 10061324
TI  - Theory of tricriticality for miscut surfaces.

PMID- 10061326
TI  - Dynamical Franz-Keldysh effect.

PMID- 10061327
TI  - Strongly localized electrons in a magnetic field: Exact results on quantum
      interference and magnetoconductance.

PMID- 10061328
TI  - Giant low temperature heat capacity of GaAs quantum wells near Landau level
      filling nu =1.

PMID- 10061329
TI  - Critical fluctuations in superconductors and the magnetic field penetration
      depth.

PMID- 10061330
TI  - Sample-specific conductance fluctuations modulated by the superconducting phase.

PMID- 10061331
TI  - Vortex shear modulus and lattice melting in twin boundary channels of YBa2Cu3O7-
      delta.

PMID- 10061333
TI  - Spectral properties of one dimensional insulators and superconductors.

PMID- 10061334
TI  - Soliton lattice in pure and diluted CuGeO3.

PMID- 10061332
TI  - Reentrant peak effect and the melting of a flux line lattice in 2H-NbSe2.

PMID- 10061335
TI  - Dynamics in the S=1/2 one-dimensional antiferromagnet Sr2CuO3 via 63Cu NMR.

PMID- 10061336
TI  - Two-dimensional ising spin glasses with nonzero ordering temperatures.

PMID- 10061337
TI  - Magnetic order-disorder transition mediated by a temperature-driven structural
      transformation.

PMID- 10061338
TI  - Positive exchange bias in FeF2-Fe bilayers.

PMID- 10061340
TI  - The homologous contraction of a sonoluminescing bubble.

PMID- 10061339
TI  - Magnetoelectric spectroscopy of electronic transitions in antiferromagnetic
      Cr2O3.

PMID- 10061341
TI  - L-shell filling rates of highly charged ions in metals.

PMID- 10061342
TI  - Neutron scattering study of depletion interactions in a colloid-polymer mixture.

PMID- 10061343
TI  - New mechanism for neural pattern formation.

PMID- 10061347
TI  - Optimization on rugged landscapes: A new general purpose Monte Carlo approach.

PMID- 10061344
TI  - Comment on "Glassiness in a model without energy barriers"

PMID- 10061348
TI  - Dense coding in experimental quantum communication.

PMID- 10061350
TI  - Generalized nonextensive thermodynamics applied to the cosmic background
      radiation in a Robertson-Walker universe.

PMID- 10061349
TI  - Dissipation and decoherence in mean field theory.

PMID- 10061351
TI  - First-order symmetric hyperbolic Einstein equations with arbitrary fixed gauge.

PMID- 10061352
TI  - Species doubling and chiral Lagrangians.

PMID- 10061353
TI  - Search for flavor-changing neutral current B meson decays in pp-bar collisions at
      sqrt s=1.8 TeV.

PMID- 10061354
TI  - Test of parity-conserving time-reversal invariance using polarized neutrons and
      nuclear spin aligned holmium.

PMID- 10061355
TI  - Double and single ionization of helium by 58-keV x rays.

PMID- 10061356
TI  - Raman-induced avoided crossings in adiabatic optical potentials: Observation of
      lambda /8 spatial frequency in the distribution of atoms.

PMID- 10061358
TI  - Intensity interference of ultrashort pulsed fluorescence.

PMID- 10061357
TI  - Excited state muon transfer in hydrogen/deuterium mixtures.

PMID- 10061359
TI  - Coherent control over Liouville-space pathways interference in transient four
      wave mixing spectroscopy.

PMID- 10061360
TI  - Detecting unstable periodic orbits in chaotic experimental data.

PMID- 10061361
TI  - Parametric correlations of scattering phase shifts and fluctuations of delay
      times in few-channel chaotic scattering.

PMID- 10061362
TI  - Generalizing the poynting vector.

PMID- 10061363
TI  - Relative particle motion in capillary waves.

PMID- 10061364
TI  - Quantitative measurements of thermal relaxation of isolated silicon hillocks and
      craters on the Si(111)-7 x 7 surface by scanning tunneling microscopy.

PMID- 10061365
TI  - Charge injection and STM-induced vacancy migration on GaAs(110).

PMID- 10061366
TI  - Weakly nonlinear theory of pattern-forming systems with spontaneously broken
      isotropy.

PMID- 10061367
TI  - Orientation of adsorbed C60 molecules determined via x-ray photoelectron
      diffraction.

PMID- 10061368
TI  - Boron nitride nanotubes with reduced numbers of layers synthesized by arc
      discharge.

PMID- 10061369
TI  - Experimental evidence for self-similar structures in the aggregation of
      porphyrins in aqueous solutions.

PMID- 10061370
TI  - Scattering of superfluid vortex rings.

PMID- 10061371
TI  - Adsorption-induced bending of a triatomic molecule: Near-edge x-ray absorption
      fine-structure spectroscopy investigation of N2O adsorbed on different Ni(111)
      surfaces.

PMID- 10061373
TI  - Chemically induced step edge diffusion barriers: Dendritic growth in 2D alloys.

PMID- 10061372
TI  - Complex dynamical phenomena in heavily arsenic doped silicon.

PMID- 10061374
TI  - Out-of-equilibrium step meandering on a vicinal surface.

PMID- 10061375
TI  - Nucleation of a complex oxide during epitaxial film growth: SmBa2Cu3Oy on SrTiO3.

PMID- 10061376
TI  - Average local order parameter in partially ordered GaInP2.

PMID- 10061377
TI  - Extremely low frequency plasmons in metallic mesostructures.

PMID- 10061379
TI  - Low frequency spectroscopy of the correlated metallic system CaxSr1 -xVO3.

PMID- 10061378
TI  - Higher-dimensional bosonization with nonlinear energy dispersion.

PMID- 10061380
TI  - Antiferromagnetic phase of the d=

PMID- 10061381
TI  - Influence of hydrostatic pressure on the insulator-metal transition in
      BaCo0.9Ni0.1S1.9.

PMID- 10061382
TI  - Spin gratings and the measurement of electron drift mobility in multiple quantum
      well semiconductors.

PMID- 10061383
TI  - Suppression of charge carrier tunneling through organic self-assembled
      monolayers.

PMID- 10061384
TI  - Degenerate Bose liquid in a fluctuating gauge field.

PMID- 10061386
TI  - Thermodynamic evidence for a flux line lattice melting transition in YBa2 Cu3O7-
      delta.

PMID- 10061385
TI  - Glass formation in a periodic long-range Josephson array.

PMID- 10061387
TI  - Correlation functions in a corner-shaped Ising model.

PMID- 10061388
TI  - Hysteresis in the incommensurate phase of the spin-Peierls compound CuGeO3:
      Electron spin resonance in high field.

PMID- 10061389
TI  - Spatial inhomogeneity and thermodynamic chaos.

PMID- 10061390
TI  - Crucial role of the lattice distortion in the magnetism of LaMnO3.

PMID- 10061391
TI  - Perturbed angular correlation measurements in 2D spin-frustrated CuFeO2.

PMID- 10061393
TI  - Biquadratic exchange coupling in sputtered (100) Fe/Cr/Fe.

PMID- 10061392
TI  - Observation and characterization of ferromagnetic amorphous nickel.

PMID- 10061394
TI  - Unconventional electronic structure evolution with hole doping in Bi2Sr2CaCu2O8+
      delta : Angle-resolved photoemission results.

PMID- 10061395
TI  - Fermi surface and extended van Hove singularity in the noncuprate superconductor
      Sr2RuO4.

PMID- 10061397
TI  - Sequential oxygen atom chemisorption on surfaces of small iron clusters.

PMID- 10061396
TI  - What happens when you leave the car lights on overnight: Violation of local
      electroneutrality in slow, steady discharge of a lead-acid cell.

PMID- 10061398
TI  - Structure and pertinent length scale of a discotic clay gel.

PMID- 10061400
TI  - First-order phase transition in a model for earthquakes.

PMID- 10061399
TI  - Statistics of kinetic pathways on biased rough energy landscapes with
      applications to protein folding.

PMID- 10061401
TI  - Phase Loss in WKB Waves Due to Reflection by a Potential.

PMID- 10061402
TI  - Diffusion of periodically forced Brownian particles moving in space-periodic
      potentials.

PMID- 10061403
TI  - Tidal Stablization of Neutron Stars and White Dwarfs.

PMID- 10061404
TI  - Prototype Direction-Sensitive Solid-State Detector for Dark Matter.

PMID- 10061405
TI  - First Study of Rapidity Gaps in e+e- Annihilation.

PMID- 10061406
TI  - Spectral Decorrelation of Nuclear Levels in the Presence of Continuum Decay.

PMID- 10061407
TI  - Properties of Very Hot Nuclei Formed in 64Zn+natTi Collisions at Intermediate
      Energies.

PMID- 10061408
TI  - Hyperfine-Induced 1s2s 1S0-1s2p 3P0 Transition and Fine-Structure Measurement in
      Heliumlike Nitrogen.

PMID- 10061409
TI  - Analytic Evaluation of the Orthopositronium-to-Three-Photon Decay Amplitudes to
      One-Loop Order.

PMID- 10061410
TI  - Periodic Orbit Origins of Dynamical Localization.

PMID- 10061411
TI  - Shape of the Tail of a Two-Dimensional Sandpile.

PMID- 10061412
TI  - Effects of Doping on the Vibrational Properties of C60 from First Principles:
      K6C60.

PMID- 10061413
TI  - Critical Phenomena of the Spin-Peierls Transition in CuGeO3.

PMID- 10061415
TI  - Dimer Shearing as a Novel Mechanism for Cluster Diffusion and Dissociation on
      Metal (100) Surfaces.

PMID- 10061414
TI  - Theoretical and Experimental Optical Spectroscopy Study of Hydrogen Adsorption at
      Si(111)-(7 x 7).

PMID- 10061416
TI  - Instability of Kinetic Roughening in Sputter-Deposition Growth of Pt on Glass.

PMID- 10061418
TI  - Intrasublattice Hopping in the Extended t-J Model and Tmaxc in the Cuprates.

PMID- 10061417
TI  - Polyacetylene in Diamond Films Evidenced by Surface Enhanced Raman Scattering.

PMID- 10061419
TI  - Subgap Structures in Intrinsic Josephson Junctions of Tl2Ba2Ca2Cu3O10+ delta and
      Bi2Sr2CaCu2O8+ delta.

PMID- 10061420
TI  - One-Dimensional Mott Insulator Formed by Quantum Vortices in Josephson Junction
      Arrays.

PMID- 10061421
TI  - Two-Dimensional Vortex Melting in BEDT Organic Superconductors and NMR Relaxation
      Induced by Vortex Structure Defects.

PMID- 10061422
TI  - Critical Behavior of the S=3/2 Antiferromagnetic Heisenberg Chain.

PMID- 10061423
TI  - The Kondo Screening Cloud: What Can We Learn from Perturbation Theory?

PMID- 10061424
TI  - Role of Orbital Polarization in Weak Ferromagnetism.

PMID- 10061425
TI  - Heavy Electrons at Metallic Fermi Surfaces, a Superlattice Property.

PMID- 10061426
TI  - Structural Investigations with the Dipolar Demagnetizing Field in Solution NMR.

PMID- 10061427
TI  - Localization of 3d and 4d Electrons in Small Clusters: The "Roots" of Magnetism.

PMID- 10061428
TI  - Interfacial Sliding of Polymer Brushes: A Molecular Dynamics Simulation.

PMID- 10061431
TI  - Periodic orbit quantization beyond the semiclassical theory.

PMID- 10061429
TI  - Branching Processes and Evolution at the Ends of a Food Chain.

PMID- 10061432
TI  - Condition of correspondence between quantum and classical dynamics for a chaotic
      system.

PMID- 10061434
TI  - Exact results for spatiotemporal correlations in a self-organized critical model
      of punctuated equilibrium.

PMID- 10061433
TI  - Solvability of some statistical mechanical systems.

PMID- 10061435
TI  - Pulsar recoil and gravitational radiation due to asymmetrical stellar collapse
      and explosion.

PMID- 10061437
TI  - CP asymmetry in the neutral B system at symmetric colliders.

PMID- 10061436
TI  - Membranes in the two-Higgs-doublet standard model.

PMID- 10061439
TI  - Medium modifications of the rho meson at CERN super proton synchrotron energies
      (200 GeV/nucleon).

PMID- 10061438
TI  - Search for the flavor-changing neutral-current decays D+--> pi + micro+ micro-
      and D+--> pi +e+e-

PMID- 10061440
TI  - Phase coexistence in multifragmentation?

PMID- 10061442
TI  - Exotic cluster states in actinide nuclei.

PMID- 10061441
TI  - Identification of T=0 and T=1 bands in the N=Z=37 nucleus 74Rb.

PMID- 10061443
TI  - High resolution spectroscopy of the hydrogen atom: Determination of the 1S Lamb
      shift.

PMID- 10061445
TI  - Close-coupling symmetrized variational continuum distorted-wave theory: Electron
      capture to excited states in p-H collisions.

PMID- 10061444
TI  - Spectral line elimination and spontaneous emission cancellation via quantum
      interference.

PMID- 10061446
TI  - Local scaling in homogeneous Hamiltonian systems.

PMID- 10061447
TI  - Parametric feedback resonance in chaotic systems.

PMID- 10061449
TI  - Exponential growth of the energy of a wave in a 1D vibrating cavity: Application
      to the quantum vacuum.

PMID- 10061448
TI  - Synchronization transitions in a disordered Josephson series array.

PMID- 10061450
TI  - Quantum cascade lasers without intersubband population inversion.

PMID- 10061451
TI  - Demonstration of soft x-ray lasing with neonlike argon and nickel-like xenon ions
      using a laser-irradiated gas puff target.

PMID- 10061452
TI  - Singular perturbation of smoothly evolving Hele-Shaw solutions.

PMID- 10061453
TI  - Active-site motion and pattern formation in self-organized interface depinning.

PMID- 10061454
TI  - Controlling domain patterns far from equilibrium.

PMID- 10061455
TI  - Radiative cooling of ion beams in storage rings by broad-band lasers.

PMID- 10061456
TI  - Li-beam-heated hohlraum experiments at Particle Beam Fusion Accelerator II.

PMID- 10061457
TI  - Dopant and temperature induced structural phase transitions in La2-xSrxCuO4.

PMID- 10061459
TI  - Charge modulation in La1.67Sr0.33NiO4: A bulk thermodynamic study.

PMID- 10061458
TI  - Direct imaging of charge modulation.

PMID- 10061460
TI  - Critical behavior of systems with many absorbing states.

PMID- 10061462
TI  - Direct measurement of surface diffusion using atom-tracking scanning tunneling
      microscopy.

PMID- 10061461
TI  - Hydrodynamic mapping of two-dimensional electric fields in monolayers.

PMID- 10061463
TI  - Rotational alignment in associative desorption of D2(v"=0 and 1) from Pd(100).

PMID- 10061464
TI  - Hydrodynamic slip: Polymer adsorption and desorption at melt/solid interfaces.

PMID- 10061465
TI  - Polarizabilities of isolated semiconductor clusters.

PMID- 10061466
TI  - Spin-dependent electronic transport in granular ferromagnets.

PMID- 10061467
TI  - Quantum transport in a multiwalled carbon nanotube.

PMID- 10061468
TI  - Energy dependence of electron lifetime in graphite observed with femtosecond
      photoemission spectroscopy.

PMID- 10061469
TI  - ac response in the nonequilibrium Anderson impurity model.

PMID- 10061470
TI  - Interaction-induced delocalization of two particles in a random potential:
      Scaling properties.

PMID- 10061471
TI  - Charge transfer induced persistent current and capacitance oscillations.

PMID- 10061472
TI  - Charge density wave in two-dimensional electron liquid in weak magnetic field.

PMID- 10061473
TI  - Theory of underdoped cuprates.

PMID- 10061474
TI  - Observation of a pair-breaking field at the Ni site in nonsuperconducting
      ReNi2B2C.

PMID- 10061475
TI  - Normal modes and soliton resonance for vortices in 2D classical antiferromagnets.

PMID- 10061476
TI  - Non-mean-field behavior of realistic spin glasses.

PMID- 10061477
TI  - Nonequilibrium magnetization near the reorientation phase transition of
      Fe/Ag(100) films.

PMID- 10061479
TI  - Observation of CH3 tunneling manifold by level-crossing NMR.

PMID- 10061478
TI  - Antiferromagnetic correlations and weak ferromagnetism in a TDAE+-C60 - single
      crystal.

PMID- 10061480
TI  - Al NMR probe of local moments induced by an Al impurity in high-Tc cuprate La
      1.85Sr0.15CuO4.

PMID- 10061481
TI  - Ultrafast electron dynamics at Cu(111): Response of an electron gas to optical
      excitation.

PMID- 10061483
TI  - Internal constraints induce localization in an isolated polymer molecule.

PMID- 10061482
TI  - Quantum confined luminescence in Si/SiO2 superlattices.

PMID- 10061484
TI  - Wave-induced chemical chaos.

PMID- 10061485
TI  - Control of voltage-dependent biomolecules via nonequilibrium kinetic focusing.

PMID- 10061486
TI  - Comment on "Quasiclassical Transport at a van Hove Singularity in Cuprate
      Superconductors"

PMID- 10061487
TI  - Newns et al. reply.

PMID- 10061490
TI  - Quantum corrections to the Thomas-Fermi theory for fractional-statistics
      particles.

PMID- 10061491
TI  - Noise enhanced stability in an unstable system.

PMID- 10061493
TI  - Black holes have no short hair.

PMID- 10061492
TI  - Magnetohydrodynamic continua and stratification induced Alfven eigenmodes in
      coronal magnetic loops.

PMID- 10061494
TI  - Looking for a cosmological constant with the Rees-Sciama effect.

PMID- 10061495
TI  - Doppler peaks in the angular power spectrum of the cosmic microwave background: A
      fingerprint of topological defects.

PMID- 10061496
TI  - Formation of topological defects with explicit symmetry breaking.

PMID- 10061497
TI  - Measurements of the proton and deuteron spin structure function g2 and asymmetry
      A2.

PMID- 10061499
TI  - Infrared laser spectrum of the Si2- anion in a silane plasma.

PMID- 10061498
TI  - Proton decay of an intruder state in 185Bi.

PMID- 10061500
TI  - Electron emission from aligned superexcited O* atoms produced in
      photodissociation of O2 in the 22.20-22.36 eV region.

PMID- 10061502
TI  - Even and odd coherent states of the motion of a trapped ion.

PMID- 10061501
TI  - Experimental observation of surface modes of quasifree clusters.

PMID- 10061503
TI  - Broken ergodicity and glassy behavior in a deterministic chaotic map.

PMID- 10061505
TI  - Direct measurement of diffusion rates in high energy synchrotrons using
      longitudinal beam echoes.

PMID- 10061504
TI  - Properties of velocity circulation in three-dimensional turbulence.

PMID- 10061506
TI  - Classical theory of nonlinear Compton scattering.

PMID- 10061507
TI  - Kinetic ballooning mode with negative shear.

PMID- 10061509
TI  - An EXAFS calculation using known four-body correlations.

PMID- 10061508
TI  - Steady-state hollow electron temperature profiles in the Rijnhuizen Tokamak
      Project.

PMID- 10061510
TI  - Devil's staircase, critical thickness, and propagating fingers in
      antiferroelectric liquid crystals.

PMID- 10061512
TI  - Penetration depths of photomobilized F atoms from a sandwich experiment.

PMID- 10061511
TI  - Orientational relaxation in a random dipolar lattice: Role of spatial density
      fluctuations in supercooled liquids.

PMID- 10061513
TI  - Coarsening mechanisms in a metal film: From cluster diffusion to vacancy
      ripening.

PMID- 10061515
TI  - Generalized gradient theory for silica phase transitions.

PMID- 10061514
TI  - NMR observation of diffusion barriers for lithium adsorbed on Ru(001).

PMID- 10061516
TI  - Giant and composition-dependent optical bowing coefficient in GaAsN alloys.

PMID- 10061517
TI  - Observation of a discontinuous transition from strong to weak localization in 1D
      granular metal wires.

PMID- 10061518
TI  - Binding of quasi-two-dimensional biexcitons.

PMID- 10061519
TI  - Electron tunneling study in the NbSe3 charge density wave state.

PMID- 10061520
TI  - Evidence of Skyrmion excitations about nu =1 in n-modulation-doped single quantum
      wells by interband optical transmission.

PMID- 10061521
TI  - Universal superconductor-insulator transition and Tc depression in Zn-substituted
      high-Tc cuprates in the underdoped regime.

PMID- 10061522
TI  - Spectroscopy of the superconducting gap in individual nanometer-scale aluminum
      particles.

PMID- 10061523
TI  - New mapping for particles on lattices with hard-core interactions.

PMID- 10061525
TI  - Low shear viscosity of a dense ionic micellar solution.

PMID- 10061524
TI  - Normal state ac Hall effect in YBa2Cu3O7 thin films.

PMID- 10061526
TI  - Overlaps between RNA secondary structures.

PMID- 10061527
TI  - Multistability and delayed recurrent loops.

PMID- 10061528
TI  - Comment on "Controlling Extended Systems of Chaotic Elements"

PMID- 10061530
TI  - Comment on "Longitudinal Superconductivity in Vortex-Line Phases: A Monte Carlo
      Study"

PMID- 10061529
TI  - Auerbach replies.

PMID- 10061531
TI  - Carneiro replies.

PMID- 10061533
TI  - Merons and Thomas precession.

PMID- 10061534
TI  - Purification of noisy entanglement and faithful teleportation via noisy channels.

PMID- 10061535
TI  - Semiclassical analysis of energy level correlations for a disordered mesoscopic
      system.

PMID- 10061536
TI  - Signature for color-octet production of JZ psi in e+e- annihilation.

PMID- 10061538
TI  - Spin structure of the nucleon in the asymptotic limit.

PMID- 10061539
TI  - Structural properties of the negative calcium ion: Binding energies and fine
      structure splitting.

PMID- 10061537
TI  - Jet production via strongly interacting color-singlet exchange in pp-bar
      collisions.

PMID- 10061540
TI  - Transverse diffusion in isotropic light slowing.

PMID- 10061541
TI  - Enhanced high-harmonic generation using 25 fs laser pulses.

PMID- 10061542
TI  - Observation of coexisting upflow and downflow hexagons in Boussinesq Rayleigh
      Benard convection.

PMID- 10061543
TI  - Slow thermal waves in impurity seeded radiative plasmas.

PMID- 10061544
TI  - Mode conversion heating and current drive experiments in TFTR.

PMID- 10061545
TI  - Microscopic structure of tetrahedral amorphous carbon.

PMID- 10061546
TI  - Numerical simulation of alpha -quartz under nonhydrostatic compression: Memory
      glass and five-coordinated crystalline phases.

PMID- 10061547
TI  - Kinetic role of a surfactant in island formation.

PMID- 10061548
TI  - Dynamical scaling and phase separation in growth models with a diffusion bias.

PMID- 10061549
TI  - Observation of Fano interference in high-pressure ice VII.

PMID- 10061550
TI  - Universality of viscoelastic phase separation in dynamically asymmetric fluid
      mixtures.

PMID- 10061551
TI  - Dynamic visualization of a metal-oxide-surface/gas-phase reaction: Time-resolved
      observation by scanning tunneling microscopy at 800 K.

PMID- 10061552
TI  - Diffusion and atomic hopping of N atoms on Ru(0001) studied by scanning tunneling
      microscopy.

PMID- 10061553
TI  - Real-time observation of the dynamics of single Pb atoms on Si(111)- (7 x 7) by
      scanning tunneling microscopy.

PMID- 10061555
TI  - Elastic scattering and the lateral resolution of ballistic electron emission
      microscopy: Focusing effects on the Au/Si interface.

PMID- 10061554
TI  - Sliding friction of solid xenon monolayers and bilayers on Ag(111).

PMID- 10061556
TI  - Anomalous Hall effect in YBa2Cu3O7.

PMID- 10061557
TI  - Correlations and disorder in arrays of magnetically coupled superconducting
      rings.

PMID- 10061558
TI  - Excitation of the Josephson plasma mode in Bi2Sr2CaCu2O8+ delta in an oblique
      field.

PMID- 10061559
TI  - Diffusive conductors as Andreev interferometers.

PMID- 10061560
TI  - Long-range fluctuation-induced attraction of vortices to the surface in layered
      superconductors.

PMID- 10061561
TI  - Structure of a moving vortex lattice.

PMID- 10061562
TI  - Discontinuity of reversible magnetization in untwinned YBCO single crystals at
      the first order vortex melting transition.

PMID- 10061563
TI  - Random bonds and topological stability in gapped quantum spin chains.

PMID- 10061564
TI  - Numerical evidence for spontaneously broken replica symmetry in 3D spin glasses.

PMID- 10061566
TI  - Autocorrelation functions of driven reaction-diffusion processes.

PMID- 10061565
TI  - Femtosecond relaxation of photoexcitations in a poly(para-phenylene)-type ladder
      polymer.

PMID- 10061567
TI  - Comment on "Relationship between the Coulomb integral U and the Stoner parameter
      I"

PMID- 10061568
TI  - Severin, Brooks, and Johansson Reply.

PMID- 10061569
TI  - Integrability, monodromy evolving deformations, and self-dual Bianchi IX systems.

PMID- 10061570
TI  - Hawking radiation and unitary evolution.

PMID- 10061571
TI  - Test of the equivalence principle from neutrino oscillation experiments.

PMID- 10061572
TI  - Implications for supersymmetry of the reported deviations from the standard model
      for Gamma (Z-->bb-bar) and alpha s(m2Z).

PMID- 10061573
TI  - Finite-temperature phase structure of lattice QCD with Wilson quark action.

PMID- 10061574
TI  - Color-octet quarkonium production at the Z pole.

PMID- 10061575
TI  - Up-down quark mass difference effect in nuclear many-body systems.

PMID- 10061576
TI  - Observation of isovector-isoscalar two-body currents in deuteron knockout from
      3He.

PMID- 10061578
TI  - Polarization independence of microwave "ionization" thresholds of excited
      hydrogen atoms near the principal resonance.

PMID- 10061577
TI  - Stability of 10050Sn50 deduced from excited states in 9948Cd51.

PMID- 10061580
TI  - Single-mode generation of quantum photon states by excited single molecules in a
      microcavity trap.

PMID- 10061579
TI  - Triple ionization of carbon monoxide.

PMID- 10061581
TI  - Synchronizing hyperchaos with a scalar transmitted signal.

PMID- 10061582
TI  - Turbulent convection over rough surfaces.

PMID- 10061583
TI  - Femtosecond x-ray pulses of synchrotron radiation.

PMID- 10061584
TI  - Experimental measurements of the current, temperature, and density profile
      changes during a disruption in the DIII-D tokamak.

PMID- 10061586
TI  - Thermotropic transition from a state of liquid order to a macrolattice in
      asymmetric diblock copolymers.

PMID- 10061585
TI  - Edge localized modes as new bifurcation in tokamaks.

PMID- 10061587
TI  - Effect of environment on hydrogen bond dynamics in liquid water.

PMID- 10061588
TI  - Role of network topology on the vibrational lifetime of an H2O molecule in the Ge
      As-Se glass series.

PMID- 10061589
TI  - Self-organized criticality and synchronization in a forest-fire model.

PMID- 10061590
TI  - Simplest possible self-organized critical system.

PMID- 10061592
TI  - Spatial probability distribution of adsorbate atoms.

PMID- 10061591
TI  - Heat capacity and thermal relaxation of bulk helium very near the lambda point.

PMID- 10061593
TI  - Vertically aligned and electronically coupled growth induced InAs islands in
      GaAs.

PMID- 10061594
TI  - The nature of a wet electron.

PMID- 10061595
TI  - Electronic structure of the perovskite oxides: La1-xCaxMnO3.

PMID- 10061596
TI  - Emergence of deep levels in n-type ZnSe under hydrostatic pressure.

PMID- 10061597
TI  - Spin motive force and Faraday law for electrons in mesoscopic rings.

PMID- 10061598
TI  - Pure carbon nanoscale devices: Nanotube heterojunctions.

PMID- 10061599
TI  - Weak field phase diagram for an integer quantum Hall liquid.

PMID- 10061600
TI  - Correlation energy and tunneling density of states in the fractional quantum Hall
      regime.

PMID- 10061601
TI  - Resistive upper critical field of high-Tc single crystals of Bi2Sr2CaCu2O8.

PMID- 10061602
TI  - Overtone vibrational dephasing in liquids studied by femtosecond fifth-order
      nonlinear spectroscopy.

PMID- 10061603
TI  - Structural determination of beta -SiC(100)-c(2 x 2) from C-1s surface-core
      exciton and Si-2p absorption.

PMID- 10061604
TI  - Scattering of rare-gas atoms at a metal surface: Evidence of anticorrugation of
      the helium-atom potential energy surface and the surface electron density.

PMID- 10061605
TI  - Biological effects of stellar collapse neutrinos
AB  - Massive stars in their final stages of collapse radiate most of their binding
      energy in the form of MeV neutrinos.  The recoil atoms that they produce in
      elastic scattering off nuclei in organic tissue create radiation damage which is
      highly effective in the production of irreparable DNA harm, leading to cellular
      mutation, neoplasia, and oncogenesis. Using a conventional model of the galaxy
      and of the collapse mechanism, the periodicity of nearby stellar collapses and
      the radiation dose are calculated. The possible contribution of this process to
      the paleontological record of mass extinctions is examined.

PMID- 10061606
TI  - Comment on "Intermittency in tokamak edge turbulence"

PMID- 10061610
TI  - Weighing the universe with the cosmic microwave background.

PMID- 10061607
TI  - Jha et al. reply.

PMID- 10061611
TI  - Nonthermal phase transitions after inflation.

PMID- 10061612
TI  - Almost-Goldstone bosons from extra-dimensional gauge theories.

PMID- 10061613
TI  - High density QCD with static quarks.

PMID- 10061615
TI  - Linking dynamical and thermal models of ultrarelativistic nuclear scattering.

PMID- 10061614
TI  - Polarized Compton scattering from the proton.

PMID- 10061616
TI  - Trapped-ion technique for measuring the nuclear charge radii of highly charged
      radioactive isotopes.

PMID- 10061617
TI  - Collective dipole motion in highly excited 272Hs (Z=108) nuclei.

PMID- 10061618
TI  - Direct determination of the quantum-mechanical density matrix using the density
      equation.

PMID- 10061619
TI  - Collective behavior of electrons emitted in multiply ionizing collisions of 5.9
      MeV/u U65+ with Ne.

PMID- 10061620
TI  - Bonding of CO to metal particles: Photoelectron spectra of Nin(CO)m - and
      Ptn(CO)m - clusters.

PMID- 10061621
TI  - Complex quantum structure of nonclassical superposition states and quantum
      instability in resonance fluorescence.

PMID- 10061622
TI  - Arbitrary control of a quantum electromagnetic field.

PMID- 10061623
TI  - Bohr-Sommerfeld quantization of periodic orbits.

PMID- 10061624
TI  - Domain coexistence in two-dimensional optical patterns.

PMID- 10061625
TI  - Observation of multiple kinetic Alfven eigenmodes.

PMID- 10061627
TI  - Direct observation of Friedel oscillations around incorporated SiGa dopants in
      GaAs by low-temperature scanning tunneling microscopy.

PMID- 10061626
TI  - First observation of alpha particle loss induced by kinetic ballooning modes in
      TFTR deuterium-tritium experiments.

PMID- 10061628
TI  - Blocking technique for emulating very large polyelectrolytes.

PMID- 10061629
TI  - No evidence for size-dependent icosahedral --> fcc structural transition in rare
      gas clusters.

PMID- 10061630
TI  - Dynamic instabilities in fracture.

PMID- 10061631
TI  - Universal properties of spectral dimension.

PMID- 10061632
TI  - Exact macroscopic description of phase segregation in model alloys with long
      range interactions.

PMID- 10061633
TI  - Quantum algebraic nature of the phonon spectrum in 4He.

PMID- 10061634
TI  - Observation of the predicted behavior of nonlinear pulse propagation in
      disordered media.

PMID- 10061636
TI  - Dewetting at the liquid-liquid interface.

PMID- 10061635
TI  - Interfacial roughening induced by phase separation.

PMID- 10061637
TI  - Microscopic theory of electromigration on semiconductor surfaces.

PMID- 10061638
TI  - Role of layering oscillations at liquid metal surfaces in bulk recrystallization
      and surface melting.

PMID- 10061639
TI  - Colossal magnetoresistance of ferromagnetic manganites: Structural tuning and
      mechanisms.

PMID- 10061640
TI  - Electronic correlations in one-dimensional superlattices.

PMID- 10061642
TI  - Cyclotron resonance of localized electron systems in the magnetic quantum limit.

PMID- 10061641
TI  - What is the Thouless energy for ballistic systems?

PMID- 10061643
TI  - Effect of adsorbed helium on electron tunneling between metal electrodes.

PMID- 10061644
TI  - Nonperturbative approach to correlations in two-dimensional vortex liquids.

PMID- 10061645
TI  - Real space renormalization group methods and quantum groups.

PMID- 10061646
TI  - k-space mapping of majority and minority bands on the Fermi surface of Nickel
      below and above the Curie temperature.

PMID- 10061647
TI  - Correct assignment of the hydrogen vibrations of the donor-hydrogen complexes in
      Si: A new example of Fermi resonance.

PMID- 10061648
TI  - Mechanisms for stable single bubble sonoluminescence.

PMID- 10061649
TI  - Reaction-induced ordering phenomena in binary polymer mixtures.

PMID- 10061651
TI  - Spiral competition in three-component excitable media.

PMID- 10061650
TI  - Precise numerics versus theory for correlation ratchets.

PMID- 10061652
TI  - Competing patterns of signaling activity in dictyostelium discoideum.

PMID- 10061653
TI  - Comment on "Asymptotic scaling in the two-dimensional O(3) sigma model at
      correlation length 10 "

PMID- 10061654
TI  - Caracciolo et al. reply:

PMID- 10061655
TI  - Commment on "Vortex nucleation in superfluid 4He"

PMID- 10061657
TI  - Diffeomorphism groups, anyon fields, and q commutators.

PMID- 10061658
TI  - Finite size and dimensional dependence in the Euclidean traveling salesman
      problem.

PMID- 10061659
TI  - Unitary evolution between pure and mixed states.

PMID- 10061660
TI  - Modular invariance of finite size corrections and a vortex critical phase.

PMID- 10061661
TI  - Determining the Cabibbo-Kobayashi-Maskawa unitarity triangle from B decays to
      charged pions and kaons.

PMID- 10061662
TI  - Possible conservation of the K-quantum number in excited rotating nuclei.

PMID- 10061663
TI  - Two-phonon octupole excitation in 208Pb.

PMID- 10061664
TI  - Excitation energies from time-dependent density-functional theory.

PMID- 10061665
TI  - Precision measurements in helium at 58 nm: Ground state lamb shift and the 1 S-2
      P transition isotope shift.

PMID- 10061666
TI  - Photoionization and Compton double ionization of helium from threshold to 20 keV.

PMID- 10061667
TI  - Femtosecond two-dimensional spectroscopy of molecular motion in liquids.

PMID- 10061669
TI  - Estimating model parameters from time series by autosynchronization.

PMID- 10061668
TI  - Fine structure effect in electron impact ionization.

PMID- 10061670
TI  - Measurements of higher order photon bunching of light beams.

PMID- 10061672
TI  - Transition undulator radiation as bright infrared source.

PMID- 10061671
TI  - Molecular dissociation in hot, dense hydrogen.

PMID- 10061673
TI  - Experimental observations of steep temperature steps in dense magnetized plasmas.

PMID- 10061674
TI  - Feedback control of major disruptions in tokamaks.

PMID- 10061675
TI  - Nonlinear dynamics of a driven mode near marginal stability.

PMID- 10061677
TI  - Two-dimensional electron magnetohydrodynamic turbulence.

PMID- 10061676
TI  - Two-dimensional convective turbulence.

PMID- 10061679
TI  - Compliance measurements of confined polystyrene solutions by atomic force
      microscopy.

PMID- 10061678
TI  - High ion temperature mode in Heliotron-E.

PMID- 10061680
TI  - Quantitative scanning tunneling microscopy at atomic resolution: Influence of
      forces and tip configuration.

PMID- 10061681
TI  - Static nonlocal dielectric function of liquid water.

PMID- 10061683
TI  - Systematic technique for the study of interphase boundaries in structural phase
      transitions.

PMID- 10061682
TI  - First principles simulation of grain boundary sliding.

PMID- 10061685
TI  - Parameterless explanation of the non-Arrhenius conductivity in glassy fast ionic
      conductors.

PMID- 10061684
TI  - First-order transition between weak and strong pinning in clean superconductors
      with enhanced spin susceptibility.

PMID- 10061686
TI  - New dissipative region below the superfluid transition of 4He in a heat current.

PMID- 10061687
TI  - New approach for determination of diffusion parameters of adatoms.

PMID- 10061688
TI  - de Haas-van Alphen effect in canonical and grand canonical multiband Fermi
      liquid.

PMID- 10061689
TI  - Incipient antiferromagnetism and low-energy excitations in the half-filled two
      dimensional Hubbard model.

PMID- 10061690
TI  - Floating of extended states and localization transition in a weak magnetic field.

PMID- 10061691
TI  - Quantum optical spin-glass state of impurity two-level atoms in a photonic band
      gap.

PMID- 10061692
TI  - Phenomenological transport equation for the cuprate metals.

PMID- 10061694
TI  - Composite fermion theory of collective excitations in fractional quantum Hall
      effect.

PMID- 10061693
TI  - Spin splitting of single 0D impurity states in semiconductor heterostructure
      Quantum Wells.

PMID- 10061695
TI  - Direct imaging of integer and half-integer Josephson vortices in high-Tc grain
      boundaries.

PMID- 10061696
TI  - Mechanism of thermally activated c-axis dissipation in layered high-Tc
      superconductors at high fields.

PMID- 10061697
TI  - Comparison of the high-frequency magnetic fluctuations in insulating and
      superconducting La2-xSrxCuO4.

PMID- 10061698
TI  - Dependence of superconducting transition temperature on doping and structural
      distortion of the CuO2 planes in La2-xMxCuO4 (M=Nd, Ca, Sr).

PMID- 10061699
TI  - High-precision evaluation of the static exponents of the classical Heisenberg
      ferromagnet.

PMID- 10061700
TI  - Lattice effects in the colossal-magnetoresistance manganites.

PMID- 10061702
TI  - Prediction of a giant dielectric anomaly in ultrathin polydomain ferroelectric
      epitaxial films.

PMID- 10061701
TI  - Fluctuation effects in low-dimensional spin-Peierls systems: Theory and
      experiment.

PMID- 10061703
TI  - Probability of reflection by a random laser.

PMID- 10061704
TI  - Large local-field corrections in optical rotatory power of quartz and selenium.

PMID- 10061705
TI  - Observation of coupled vibrational modes of a semiconductor nanocrystal.

PMID- 10061706
TI  - One-step and two-step description of deexcitation processes in weakly interacting
      systems.

PMID- 10061707
TI  - Rotating chemical waves in small circular domains.

PMID- 10061708
TI  - Direct chemisorption site selectivity for molecular halogens on the Si(111)-(7 x
      7) surface.

PMID- 10061709
TI  - Hydrodynamic screening in sedimenting suspensions of non-Brownian spheres.

PMID- 10061710
TI  - Polydispersity and ordered phases in solutions of rodlike macromolecules.

PMID- 10061711
TI  - Comment on "Negative transport lifetime of electrons in quantum wires"

PMID- 10061712
TI  - Telang and Bandyopadhyay Reply.

PMID- 10061713
TI  - Comment on "Phase controlled conductance of mesoscopic structures with
      superconducting mirrors"

PMID- 10061715
TI  - Moment of inertia and superfluidity of a trapped Bose gas.

PMID- 10061716
TI  - Chaos around a Henon-Heiles-inspired exact perturbation of a black hole.

PMID- 10061717
TI  - Causality, randomness, and the microwave background.

PMID- 10061718
TI  - On the convergence of perturbative QCD at high temperature.

PMID- 10061719
TI  - Search for the decay K+--> pi + nu nu -bar.

PMID- 10061720
TI  - Importance of one- and two-body dissipation at intermediate energies studied by
      hard photons.

PMID- 10061721
TI  - Missing isoscalar monopole strength in 58Ni.

PMID- 10061722
TI  - Self-energy correction to the hyperfine structure splitting of hydrogenlike
      Atoms.

PMID- 10061723
TI  - Electron correlation in multiple excitation of atoms by high-energy ions.

PMID- 10061724
TI  - Surface-enhanced magnetism in nickel clusters.

PMID- 10061725
TI  - New spectroscopic tool for cluster science: Nonexponential laser fluence
      dependence of photofragmentation.

PMID- 10061726
TI  - Local optimal metrics and nonlinear modeling of chaotic time series.

PMID- 10061728
TI  - Optical wave-packet propagation in nonisotropic media.

PMID- 10061727
TI  - Overcoming the wall in the semiclassical Baker's map.

PMID- 10061729
TI  - Passive scalars, random flux, and chiral phase fluids.

PMID- 10061731
TI  - Helicity and transport in electron MHD heat pulses.

PMID- 10061730
TI  - Thermal turbulence in mercury.

PMID- 10061732
TI  - Quantitative study of the ionization-induced refraction of picosecond laser
      pulses in gas-jet targets.

PMID- 10061734
TI  - Directed surfaces in disordered media.

PMID- 10061733
TI  - Structure in a confined smectic liquid crystal with competing surface and sample
      elasticities.

PMID- 10061735
TI  - Apparent barrier height in scanning tunneling microscopy revisited.

PMID- 10061736
TI  - Superspace groups without the embedding: The link between superspace and Fourier
      space crystallography.

PMID- 10061738
TI  - Stability of quasiequilibrium cracks under uniaxial loading.

PMID- 10061737
TI  - Trap-limited migration of Si self-interstitials at room temperature.

PMID- 10061739
TI  - Formation of AgHe2 exciplex in liquid helium.

PMID- 10061740
TI  - Boundary effects on spectral properties of interacting electrons in one
      dimension.

PMID- 10061741
TI  - Effective sigma model formulation for two interacting electrons in a disordered
      metal.

PMID- 10061742
TI  - Exciton dynamics in poly(p-pyridyl vinylene).

PMID- 10061743
TI  - Electronic energy transfer in CdSe quantum dot solids.

PMID- 10061744
TI  - In situ measurements of interface states at silicon surfaces in fluoride
      solutions.

PMID- 10061746
TI  - Observation of quantum dissipation in the vortex state of a highly disordered
      superconducting thin film.

PMID- 10061745
TI  - Grazing incidence infrared reflectivity of La1.85Sr0.15CuO4 and NbN.

PMID- 10061747
TI  - Electronic excitations in Bi2Sr 2CaCu2O8: Fermi surface, dispersion, and absence
      of bilayer splitting.

PMID- 10061748
TI  - Observation of magnetism and Kondo effect for Sc ions in metallic hosts.

PMID- 10061749
TI  - Magnetic order in two-dimensional arrays of nanometer-sized superparamagnets.

PMID- 10061750
TI  - Femtosecond carrier dynamics in GaAs far from equilibrium.

PMID- 10061751
TI  - Magnetic field diagnostic for sonoluminescence.

PMID- 10061752
TI  - Comment on "Dynamic viscosity of a simple glass-forming liquid"

PMID- 10061754
TI  - Comment on "Superconductivity in bad metals"

PMID- 10061753
TI  - Menon, Nagel, and Venerus reply.

PMID- 10061755
TI  - Influence of s-d exchange interaction on universal conductance fluctuations in
      Cd1-xMnxTe:In

PMID- 10061756
TI  - Average Entropy of a Quantum Subsystem.

PMID- 10061757
TI  - Atomic Wave Diffraction and Interference Using Temporal Slits.

PMID- 10061758
TI  - Universal Scaling Functions for Numbers of Percolating Clusters on Planar
      Lattices.

PMID- 10061759
TI  - Energy-Dependent Polarization Variability as a Black Hole Signature.

PMID- 10061760
TI  - QCD Corrections to Supersymmetric Higgs Boson Production: The Role of Squark
      Loops.

PMID- 10061761
TI  - Implications of the B-->X

PMID- 10061762
TI  - Temperature Dependence of the Coupling of Nucleons to the Nuclear Surface.

PMID- 10061763
TI  - New Type of Collective Motion for N~Z Nuclei.

PMID- 10061764
TI  - New Spontaneous Fission Mode for 252Cf: Indication of Hyperdeformed 144,145,146Ba
      at Scission.

PMID- 10061766
TI  - Propagating Elementary Excitation in a Dilute Optical Lattice.

PMID- 10061765
TI  - alpha Decay of Deformed Actinide Nuclei.

PMID- 10061767
TI  - Angular Momentum of Supersymmetric Cold Rydberg Atoms.

PMID- 10061768
TI  - Atom-Molecule Scattering: Classical Simplicity beneath Quantum Complexity.

PMID- 10061769
TI  - Dimer Growth, Structural Transition, and Antiferromagnetic Ordering of Small
      Chromium Clusters.

PMID- 10061770
TI  - Riddling Bifurcation in Chaotic Dynamical Systems.

PMID- 10061772
TI  - Noise and Dynamical Pattern Selection.

PMID- 10061771
TI  - Exponential Divergence and Long Time Relaxation in Chaotic Quantum Dynamics.

PMID- 10061773
TI  - Thomson Scattering Measurements of the Langmuir Wave Spectra Resulting from
      Stimulated Raman Scattering.

PMID- 10061774
TI  - Scalings of Ion-Temperature-Gradient-Driven Anomalous Transport in Tokamaks.

PMID- 10061775
TI  - Experimental Confirmation of Ponderomotive-Force Electrons Produced by an
      Ultrarelativistic Laser Pulse on a Solid Target.

PMID- 10061776
TI  - Onset and Saturation of the Spectral Intensity of Stimulated Brillouin Scattering
      in Inhomogeneous Laser-Produced Plasmas.

PMID- 10061777
TI  - Transition from Normal to Fast Sound in Liquid Water.

PMID- 10061778
TI  - Homoepitaxial Growth of Pt on Pt(100)-hex: Effects of Strongly Anisotropic
      Diffusion and Finite Island Sizes.

PMID- 10061780
TI  - Density Profile of Spherical Polymer Brushes.

PMID- 10061779
TI  - Nanometer-Scale Creation and Characterization of Trapped Charge in SiO2 Films
      Using Ballistic Electron Emission Microscopy.

PMID- 10061781
TI  - Size-Dependent Melting Properties of Small Tin Particles: Nanocalorimetric
      Measurements.

PMID- 10061782
TI  - Inversion Domain and Stacking Mismatch Boundaries in GaN.

PMID- 10061783
TI  - Tracer Dispersion in a Self-Organized Critical System.

PMID- 10061784
TI  - Universality in Sandpiles, Interface Depinning, and Earthquake Models.

PMID- 10061786
TI  - Structure of the As Vacancies on GaAs(110) Surfaces.

PMID- 10061785
TI  - Kinetic Energy of Liquid and Solid 4He.

PMID- 10061787
TI  - Existence of a 'Hot' Atom Mechanism for the Dissociation of O2 on Pt(111).

PMID- 10061788
TI  - Giant Surface Stress in Heteroepitaxial Films: Invalidation of a Classical Rule
      in Epitaxy.

PMID- 10061789
TI  - New Iterative Perturbation Scheme for Lattice Models with Arbitrary Filling.

PMID- 10061790
TI  - Possible Spin Polarization in a One-Dimensional Electron Gas.

PMID- 10061791
TI  - Matrix Treatment of Electrical Current: Current Echoes.

PMID- 10061792
TI  - Low Frequency Admittance of a Quantum Point Contact.

PMID- 10061793
TI  - Anisotropic Magnetoresistance of a Classical Antidot Array.

PMID- 10061794
TI  - Thermopower of Cuprate Superconductors under Hydrostatic Pressure.

PMID- 10061795
TI  - Implications of Charge Ordering for Single-Particle Properties of High-Tc
      Superconductors.

PMID- 10061796
TI  - Size Effects in Flow of Flux-Line Solids and Liquids.

PMID- 10061797
TI  - Breakdown of de Gennes Scaling in (R1-xR'x)Ni2B2C Compounds.

PMID- 10061798
TI  - Tc vs Carrier Concentration in Cubic Fulleride Superconductors.

PMID- 10061799
TI  - Path-Summation Representations in Planar Uniaxial Ferromagnets.

PMID- 10061800
TI  - Dynamic Jahn-Teller Effect and Colossal Magnetoresistance in La 1-xSrxMnO3.

PMID- 10061801
TI  - Direct Hopf Bifurcation in Parametric Resonance of Hybridized Waves.

PMID- 10061802
TI  - Nuclear Exciton Echo Produced by Ultrasound in Forward Scattering of Synchrotron
      Radiation.

PMID- 10061803
TI  - Visible-Light-Emitting Layered BC2N Semiconductor.

PMID- 10061805
TI  - Chemically Driven Motility of Brownian Particles.

PMID- 10061804
TI  - Breathing Spots in a Reaction-Diffusion System.

PMID- 10061806
TI  - Perfect Quantum Error Correcting Code.

PMID- 10061807
TI  - Comment on "Observation of Continuum-Continuum Autler-Townes Splitting"

PMID- 10061808
TI  - Walker et al. Reply.

PMID- 10061809
TI  - Comment on "Pressure-Induced Intercalation and Amorphization in the Spin-Peierls
      Compound CuGeO3"

PMID- 10061810
TI  - Jayaraman et al. Reply.

PMID- 10061811
TI  - Excitation of an Atomic Electron to a Coherent Superposition of Macroscopically
      Distinct States.

PMID- 10061812
TI  - Can Two-Photon Interference be Considered the Interference of Two Photons?

PMID- 10061813
TI  - Solution of a Coupled Channel Inverse Scattering Problem at Fixed Energy by a
      Modified Newton-Sabatier Method.

PMID- 10061814
TI  - Stochastic Resonance with Sensitive Frequency Dependence in Globally Coupled
      Continuous Systems.

PMID- 10061815
TI  - Back Reaction and Graceful Exit in String Inflationary Cosmology.

PMID- 10061816
TI  - Non-Gaussian Fixed Point in Four-Dimensional Pure Compact U(1) Gauge Theory on
      the Lattice.

PMID- 10061818
TI  - Inclusive Jet ET Distributions and Light Gluinos.

PMID- 10061817
TI  - Probing Lepton Flavor Violation at Future Colliders.

PMID- 10061820
TI  - Shell Model Studies of the Double Beta Decays of 76Ge, 82Se, and 136Xe.

PMID- 10061819
TI  - Measurement of the Lifetime of the B0s Meson Using the Exclusive Decay Mode B0s-
      >J/ psi phi.

PMID- 10061822
TI  - Electron Cooling of Protons in a Nested Penning Trap.

PMID- 10061821
TI  - Giant Microwave Absorption in Metallic Grains: Relaxation Mechanism.

PMID- 10061823
TI  - Ionization and Fragmentation of C60 via Multiphoton-Multiplasmon Excitation.

PMID- 10061824
TI  - Model of Quantum Chaotic Billiards: Spectral Statistics and Wave Functions in Two
      Dimensions.

PMID- 10061825
TI  - Lyapunov Exponents from Kinetic Theory for a Dilute, Field-Driven Lorentz Gas.

PMID- 10061826
TI  - Plasma Response to Strongly Sheared Flow.

PMID- 10061827
TI  - Generation of Large Area, Sheet Plasma Mirrors for Redirecting High Frequency
      Microwave Beams.

PMID- 10061828
TI  - Molecular Imaging and Local Density of States Characterization at the
      Si(111)/NaOH Interface.

PMID- 10061829
TI  - Temperature Gradients Induced Phase Separation in a Miscible Polymer Solution.

PMID- 10061830
TI  - Wetting and Anchoring of a Nematic Liquid Crystal on a Rough Surface.

PMID- 10061831
TI  - Thermopower of Decagonal Al73Ni17Co10 Single Quasicrystals: Evidence for a
      Strongly Enhanced Electron-Phonon Coupling in the Quasicrystalline Plane.

PMID- 10061832
TI  - Effect of Free Surfaces on the Glass Transition Temperature of Thin Polymer
      Films.

PMID- 10061833
TI  - Observation of Exploding Electron Bubbles in Liquid Helium.

PMID- 10061834
TI  - Strain in Nanoscale Germanium Hut Clusters on Si(001) Studied by X-Ray
      Diffraction.

PMID- 10061835
TI  - Atomic Structure of the beta -SiC(100)-(3 x 2) Surface.

PMID- 10061836
TI  - Stress-Driven Alloy Decomposition during Step-Flow Growth.

PMID- 10061837
TI  - Strain-Direction-Dependent Growth Morphology of Vicinal Si(001) Surface.

PMID- 10061838
TI  - Confined Phonons in Metallic Superlattices: Raman Study of Co/Ru.

PMID- 10061839
TI  - Density Functional for van der Waals Forces at Surfaces.

PMID- 10061841
TI  - Current-Dependent Exchange-Correlation Potential for Dynamical Linear Response
      Theory.

PMID- 10061840
TI  - Dynamics of Long-Lived Polarons in Poly(para-phenylene)-Type Ladder Polymers.

PMID- 10061842
TI  - Spin-Polarized Intergrain Tunneling in La2/3Sr1/3MnO3.

PMID- 10061843
TI  - Electrical Conductivity in Dynamically Orientationally Disordered Systems: ac and
      dc Measurements in Ferromagnetic Single Crystals of TDAE-C60.

PMID- 10061844
TI  - New Hydrogen Distribution in a-Si:H: An NMR Study.

PMID- 10061845
TI  - Conduction-Valence Landau Level Mixing Effect.

PMID- 10061846
TI  - Mesoscopic Fluctuations of Elastic Cotunneling.

PMID- 10061847
TI  - Textured Edges in Quantum Hall Systems.

PMID- 10061848
TI  - Metallic In-Plane and Divergent Out-of-Plane Resistivity of a High-Tc Cuprate in
      the Zero-Temperature Limit.

PMID- 10061849
TI  - Magnetic Excitations of the Doped-Hole State in Diamagnetic La2Cu0.5Li0.5O4.

PMID- 10061850
TI  - Static and Dynamic Vortex Phases in YBa2Cu3O7- delta.

PMID- 10061851
TI  - Metastability and Glassy Behavior of a Driven Flux-Line Lattice.

PMID- 10061852
TI  - Optical Evidence for the Dynamic Jahn-Teller Effect in Nd0.7Sr0.3MnO3.

PMID- 10061853
TI  - Interaction-Induced Spin Coplanarity in a Kagome Magnet: SrCr9pGa 12-9pO19.

PMID- 10061854
TI  - Optically Induced Polarization Anisotropy in Porous Si.

PMID- 10061855
TI  - Detection of Interstitial Oxygen Molecules in SiO2 Glass by a Direct
      Photoexcitation of the Infrared Luminescence of Singlet O2.

PMID- 10061856
TI  - Increased Elemental Specificity of Positron Annihilation Spectra.

PMID- 10061857
TI  - Sulfur K-Edge X-Ray-Absorption Study of the Charge Transfer upon Lithium
      Intercalation into Titanium Disulfide.

PMID- 10061858
TI  - Transition from Simple Rotating Chemical Spirals to Meandering and Traveling
      Spirals.

PMID- 10061860
TI  - Scanning Tunneling Microscopy Manipulation of Native Substrate Atoms: A New Way
      to Obtain Registry Information on Foreign Adsorbates.

PMID- 10061859
TI  - Domain Growth and Reaction Kinetics in Adsorbed Overlayers.

PMID- 10061861
TI  - Formation of a Highly Ordered Colloidal Microstructure upon Flow Cessation from
      High Shear Rates.

PMID- 10061862
TI  - Shear-Induced Gelation and Fracture in Micellar Solutions.

PMID- 10061863
TI  - Segregation in a One-Dimensional Model of Interacting Species.

PMID- 10061864
TI  - Self-Organized Collective Displacements of Self-Driven Individuals.

PMID- 10061866
TI  - Quantum Cryptography Based on Two Mixed States.

PMID- 10061865
TI  - Phase Transition and Phase Segregation in a Single Double-Stranded DNA Molecule.

PMID- 10061867
TI  - Model for the Leading Waves of Tsunamis.

PMID- 10061868
TI  - Comment on "Vortex Glass and Lattice Melting Transitions in a YNi2B2C Single
      Crystal"

PMID- 10061869
TI  - Mun, Lee, and Lee Reply.

PMID- 10061872
TI  - Fringe Visibility and Which-Way Information: An Inequality.

PMID- 10061871
TI  - Can a Local Repulsive Potential Trap an Electron?

PMID- 10061873
TI  - Collapses and Revivals of Bose-Einstein Condensates Formed in Small Atomic
      Samples.

PMID- 10061875
TI  - Are Nontopological Strings Produced at the Electroweak Phase Transition?

PMID- 10061874
TI  - Noise-Controlled Resonance Behavior in Nonlinear Dynamical Systems with Broken
      Symmetry.

PMID- 10061876
TI  - Limits on Spin-Mass Couplings within the Axion Window.

PMID- 10061877
TI  - Exact Solution of the One-Dimensional Non-Abelian Coulomb Gas at Large N.

PMID- 10061879
TI  - Three-Jet Cross Section in Hadron Collisions at Next-to-Leading Order: Pure Gluon
      Processes.

PMID- 10061878
TI  - Systematics of Soft Final State Interactions in B Decays.

PMID- 10061880
TI  - Time-Dependent Calculation of Photoelectron Spectra in Mg Involving Multiple
      Continua.

PMID- 10061881
TI  - Adiabatic Transfer between Hyperfine Levels in Combined Electric and Magnetic
      Fields.

PMID- 10061883
TI  - Endoscopy in the Paul Trap: Measurement of the Vibratory Quantum State of a
      Single Ion.

PMID- 10061882
TI  - First Photoexcitation Measurements and R-Matrix Calculations of Even-Parity
      Hollow States in Laser-Excited Lithium Atoms.

PMID- 10061884
TI  - Phase Conjugation of Weak Continuous-Wave Optical Signals.

PMID- 10061886
TI  - Gaussian Pulse Propagation in a Dispersive, Absorbing Dielectric.

PMID- 10061885
TI  - Synchronizing Spatiotemporal Chaos in Coupled Nonlinear Oscillators.

PMID- 10061887
TI  - Turbulent Bursts in Couette-Taylor Flow.

PMID- 10061888
TI  - Statistical Dependence of Inertial Range Properties on Large Scales in a High
      Reynolds-Number Shear Flow.

PMID- 10061889
TI  - Turbulent Pressure Structure Function.

PMID- 10061890
TI  - Molecular Chaos, Pair Correlations, and Shear-Induced Ordering of Hard Spheres.

PMID- 10061891
TI  - Multiple Light Scattering in Nematic Liquid Crystals.

PMID- 10061892
TI  - Observation of Light Diffusion and Correlation Transport in Nematic Liquid
      Crystals.

PMID- 10061893
TI  - Simultaneous Observation of Electric Field Coupling to Longitudinal and
      Transverse Ferroelectricity in a Chiral Liquid Crystal.

PMID- 10061894
TI  - Amorphization and Fracture in Silicon Diselenide Nanowires: A Molecular Dynamics
      Study.

PMID- 10061895
TI  - Conductance and Mechanical Properties of Atomic-Size Metallic Contacts: A Simple
      Model.

PMID- 10061896
TI  - Perturbation Theory for Classical Solids.

PMID- 10061898
TI  - O Binding Sites on Stepped Pt(111) Surfaces.

PMID- 10061897
TI  - Molecular Dynamics Simulation of Spinodal Decomposition in Three-Dimensional
      Binary Fluids.

PMID- 10061900
TI  - Density-Polarization-Functional Theory and Long-Range Correlation in Dielectrics.

PMID- 10061899
TI  - Glasslike Transition of a Confined Simple Fluid.

PMID- 10061901
TI  - Multiple Plasmon Satellites in Na and Al Spectral Functions from Ab Initio
      Cumulant Expansion.

PMID- 10061902
TI  - Magnetic Focusing of Composite Fermions through Arrays of Cavities.

PMID- 10061903
TI  - Asymmetric Nonlinear Differential Resistance of Mesoscopic AuFe Spin-Glass Wires.

PMID- 10061904
TI  - Sign Change of c-Axis Magnetoconductivity in YBa2Cu3O7- delta Single Crystals.

PMID- 10061905
TI  - Unconventional s-Pairing Wave Superconductivity.

PMID- 10061906
TI  - Coupling to Optical Phonons in the One-Dimensional t-J Model: Effects on the
      Superconducting Fluctuations and Phase Separation.

PMID- 10061908
TI  - Low-Temperature Upper-Critical-Field Anomalies in Clean Superconductors.

PMID- 10061907
TI  - Voltage Rectification by a SQUID Ratchet.

PMID- 10061909
TI  - Field-Driven Topological Glass Transition in a Model Flux Line Lattice.

PMID- 10061911
TI  - Magnetization Wrinkle in Thin Ferromagnetic Films.

PMID- 10061910
TI  - Suppression of the Superconducting Condensate in the High-Tc Cuprates by Zn
      Substitution and Overdoping: Evidence for an Unconventional Pairing State.

PMID- 10061912
TI  - Surface Dynamics of Liquids in Nanopores.

PMID- 10061913
TI  - Concentration Dependence of Linear Self-Assembly and Exactly Solvable Models.

PMID- 10061914
TI  - Gyrotron Experiments Employing a Field Emission Array Cathode.

PMID- 10061915
TI  - Entropic Barriers, Frustration, and Order: Basic Ingredients in Protein Folding.

PMID- 10061916
TI  - Effect of Nutrient Diffusion and Flow on Coral Morphology.

PMID- 10061917
TI  - Comment on "Confirmation of the Sigma Meson"

PMID- 10061918
TI  - Tornqvist and Roos Reply.

PMID- 10061919
TI  - Comment on "Observation of the Transition from Thomson to Compton Scattering in
      Multiphoton Interactions with Low-Energy Electrons"

PMID- 10061920
TI  - Moore, Knauer, and Meyerhofer Reply.

PMID- 10061921
TI  - Comment on "Creating Metastable Schrodinger Cat States"

PMID- 10061922
TI  - Milburn replies.

PMID- 10061923
TI  - Comment on "First-Order Transition in Random-Field Ising Systems"

PMID- 10061924
TI  - Hill et al. Reply.

PMID- 10061925
TI  - Comment on "Specific Heat of Random-Field Ising Systems"

PMID- 10061926
TI  - Comment on "X-Ray and Neutron Scattering, Magnetization, and Heat Capacity Study
      of the 3D Random Field Ising Model"

PMID- 10061927
TI  - Birgeneau et al. Reply.

PMID- 10061931
TI  - Asymptotic Integrability of Water Waves.

PMID- 10061932
TI  - Complementarity and Fundamental Limit in Precision Phase Measurement.

PMID- 10061933
TI  - Multiple Beam Atomic Interferometer.

PMID- 10061934
TI  - Collective Excitations of a Trapped Bose-Condensed Gas.

PMID- 10061935
TI  - Thermal Ratchets in 1+1 Dimensions.

PMID- 10061936
TI  - Counting States of Near-Extremal Black Holes.

PMID- 10061938
TI  - Quarkonium Decay Matrix Elements from Quenched Lattice QCD.

PMID- 10061937
TI  - Gamma Rays from SN 1987A due to Pseudoscalar Conversion.

PMID- 10061939
TI  - Search for the Flavor Changing Neutral Current Decay D0--> micro+ micro- in 800
      GeV Proton-Silicon Interactions.

PMID- 10061940
TI  - Search for D0D-bar0 Mixing in Semileptonic Decay Modes.

PMID- 10061941
TI  - Forward Cross Sections for Production of D+, D0, Ds, D*+, and Lambda c in 250 GeV
      pi +/-, K+/-, and p Interactions with Nuclei.

PMID- 10061942
TI  - Feynman-x and Transverse Momentum Dependence of D Meson Production in 250 GeV pi,
      K, and p Interactions with Nuclei.

PMID- 10061943
TI  - Forward-Angle 3He(e,e' pi +/-) Coincident Electroproduction and the Search for
      Delta 's in the Ground State of 3He.

PMID- 10061944
TI  - Mass Measurement of 100Sn.

PMID- 10061945
TI  - Observation of Fine Structure in Nuclear Level Densities and gamma -Ray Strength
      Functions.

PMID- 10061947
TI  - Photonic Band Structure of Atomic Lattices.

PMID- 10061946
TI  - Pionic Fusion of Heavy Ions.

PMID- 10061948
TI  - Product State Control through Interfering Excitation Routes.

PMID- 10061950
TI  - Multiphoton Resonance with One to Many Cycles.

PMID- 10061949
TI  - New States of Hydrogen in a Circularly Polarized Electromagnetic Field.

PMID- 10061951
TI  - New Method for Treating Slow Multielectron, Multicenter Atomic Collisions.

PMID- 10061952
TI  - Branching Ratios for Dissociative Recombination of 15N14 N+

PMID- 10061953
TI  - Evolution of the Electronic Structure of Small Vanadium Clusters from Molecular
      to Bulklike.

PMID- 10061954
TI  - Plasmon Enhanced Electron and Atom Emission from a Spherical Sodium Cluster: Na91

PMID- 10061955
TI  - Sum Rule for Modified Spontaneous Emission Rates.

PMID- 10061956
TI  - Quasiclassical Random Matrix Theory.

PMID- 10061958
TI  - Walking Solitons in Quadratic Nonlinear Media.

PMID- 10061957
TI  - Phase Diffusion in Localized Spatio-Temporal Amplitude Chaos.

PMID- 10061959
TI  - Elastic Instability and Curved Streamlines.

PMID- 10061960
TI  - Symmetry and Scaling of Turbulent Mixing.

PMID- 10061961
TI  - Crossover from Two- to Three-Dimensional Turbulence.

PMID- 10061962
TI  - Radiographic Evidence for k-5/3 Scaling of Density Power Spectra.

PMID- 10061963
TI  - Chaotic Localized States near the Onset of Electroconvection.

PMID- 10061964
TI  - Ion Transport in Turbulent Edge Plasmas.

PMID- 10061965
TI  - Interaction Physics of the Fast Ignitor Concept.

PMID- 10061966
TI  - High Confinement and High Density with Stationary Plasma Energy and Strong Edge
      Radiation in the TEXTOR-94 Tokamak.

PMID- 10061968
TI  - Mechanical Instability of Oxidized Metal Clusters.

PMID- 10061967
TI  - Theory of the Anomalous Rayleigh Dispersion at H/W(110) Surfaces.

PMID- 10061969
TI  - Frequency Dependent Electrorheological Properties: Origin and Bounds.

PMID- 10061970
TI  - Self-Organization and Annealed Disorder in Fracturing Process.

PMID- 10061971
TI  - First-Order Transitions and Hexatic Ordering in the Aerogel-Confined Liquid
      Crystal 650BC.

PMID- 10061972
TI  - Observation of 2D Polarons and Magnetopolarons on Superfluid Helium Films.

PMID- 10061973
TI  - Evidence of 4He Crystallization via Quantum Tunneling at mK Temperatures.

PMID- 10061974
TI  - Experimental and Theoretical Study of the Rotation of Si Ad-dimers on the Si(100)
      Surface.

PMID- 10061975
TI  - Real-Time Microscopy of Two-Dimensional Critical Fluctuations: Disordering of the
      Si(113)-(3 x 1) Reconstruction.

PMID- 10061976
TI  - Growth of Wetting Layers from Liquid Mixtures.

PMID- 10061978
TI  - Far-Infrared Radiation Generated by Current Carrying Nanowires.

PMID- 10061977
TI  - Direct Observation of the Magnetic-Breakdown Induced Quantum Interference in the
      Quasi-Two-Dimensional Organic Metal kappa -( BEDT -TTF )2Cu(NCS)2.

PMID- 10061979
TI  - Observation of Chiral Luttinger Behavior in Electron Tunneling into Fractional
      Quantum Hall Edges.

PMID- 10061980
TI  - Direct Observation of the Current-Phase Relation of an Adjustable Superconducting
      Point Contact.

PMID- 10061981
TI  - Phonon-Induced Spin Flip in Extremely Thin Superconducting Al Tunneling Junctions
      in High Magnetic Fields.

PMID- 10061982
TI  - Spin-Orbit Scattering Effects on the Phonon Emission and Absorption in
      Superconducting Tunneling Junctions.

PMID- 10061983
TI  - Spin Diffusion in 2D XY Ferromagnet with Dipolar Interaction.

PMID- 10061984
TI  - Origin of Spin Gap in CaV4O9: Effects of Frustration and Lattice Distortions.

PMID- 10061985
TI  - Chaos in the Ferromagnetic Phase of a Reentrant Ferromagnet.

PMID- 10061986
TI  - Film Stress and Domain Wall Pinning in Sesquilayer Iron Films on W(110).

PMID- 10061987
TI  - Symmetry-Induced Magnetic Anisotropy in Fe Films Grown on Stepped Ag(001).

PMID- 10061988
TI  - Coherent Control of Collisional Events: Bimolecular Reactive Scattering.

PMID- 10061989
TI  - Observations of First-Order Liquid-to-Hexatic and Hexatic-to-Solid Phase
      Transitions in a Confined Colloid Suspension.

PMID- 10061990
TI  - Radial Distribution Function of Semiflexible Polymers.

PMID- 10061991
TI  - Quantum Error Correction for Communication.

PMID- 10061992
TI  - Comment on "Thermodynamics of Anomalous Diffusion"

PMID- 10061993
TI  - Zanette and Alemany Reply.

PMID- 10061994
TI  - Comment on "Ground State Structural Anomalies in Cuprous Halides: CuCl"

PMID- 10061995
TI  - Park and Chadi Reply.

PMID- 10061996
TI  - Comment on "Detection of Compressible and Incompressible States in Quantum Dots
      and Antidots by Far-Infrared Spectroscopy"

PMID- 10061997
TI  - Bollweg, Kurth, Heitmann, and Gudmundsson Reply.

PMID- 10061999
TI  - Positive Quantum Brownian Evolution.

PMID- 10061998
TI  - Local Spin-Gauge Symmetry of the Bose-Einstein Condensates in Atomic Gases.

PMID- 10062000
TI  - Defect Lines in the Ising Model and Boundary States on Orbifolds.

PMID- 10062001
TI  - Burgers Velocity Fields and Dynamical Transport Processes.

PMID- 10062002
TI  - Three-Family SO(10) Grand Unification in String Theory.

PMID- 10062003
TI  - Forward-Backward Charge Asymmetry of Electron Pairs above the Z0 Pole.

PMID- 10062004
TI  - Theorem on the Lightest Glueball State.

PMID- 10062005
TI  - Single-Spin Asymmetries in Inclusive Charged Pion Production by Transversely
      Polarized Antiprotons.

PMID- 10062006
TI  - Measurement of Tensor Analyzing Powers for Elastic Electron Scattering from a
      Polarized 2H Target Internal to a Storage Ring.

PMID- 10062007
TI  - Charge Correlations and Dynamical Instabilities in the Multifragment Emission
      Process.

PMID- 10062008
TI  - Path-Integral Monte Carlo Scheme for Rigid Tops: Application to the Quantum
      Rotator Phase Transition in Solid Methane.

PMID- 10062009
TI  - Magnetic Dichroism in the Angular Distribution of Atomic Oxygen 2p
      Photoelectrons.

PMID- 10062011
TI  - Partitioning of Momentum in Electron-Impact Double Ionization of Magnesium.

PMID- 10062010
TI  - Interference Effects in the Auger Decay of the Resonantly Excited 2p3/2-13d State
      of Argon.

PMID- 10062012
TI  - Direct Evidence for the Sequential Decay C60z+-->C58z+-->C56z+ -->.

PMID- 10062014
TI  - Semiclassical Quantization of Nonseparable Systems Without Periodic Orbits.

PMID- 10062013
TI  - Magnetic Tomography of a Cavity State.

PMID- 10062015
TI  - Radiative Corrections and Quantum Chaos.

PMID- 10062017
TI  - Dissipation Independence of the Inertial-Convective Range in a Passive Scalar
      Model.

PMID- 10062016
TI  - Full Photonic Band Gap for Surface Modes in the Visible.

PMID- 10062018
TI  - Phase Defects as a Measure of Disorder in Traveling-Wave Convection.

PMID- 10062019
TI  - Role of Lobes in Chaotic Mixing of Miscible and Immiscible Impurities.

PMID- 10062020
TI  - Single-Mode Operations of a Circular Free-Electron Laser.

PMID- 10062021
TI  - Observation of Energy Gain at the BNL Inverse Free-Electron-Laser Accelerator.

PMID- 10062022
TI  - Overcoming the Backreaction on Turbulent Motions in the Presence of Magnetic
      Fields.

PMID- 10062023
TI  - Phase Transition between Coherent and Incoherent Three-Wave Interactions.

PMID- 10062024
TI  - Observed Dependence of Stimulated Raman Scattering on Ion-Acoustic Damping in
      Hohlraum Plasmas.

PMID- 10062025
TI  - Effect of Ion-Wave Damping on Stimulated Raman Scattering in High-Z Laser
      Produced Plasmas.

PMID- 10062026
TI  - Resistive Interchange Modes in Negative Central Shear Tokamaks with Peaked
      Pressure Profiles.

PMID- 10062027
TI  - Higher Fusion Power Gain with Current and Pressure Profile Control in Strongly
      Shaped DIII-D Tokamak Plasmas.

PMID- 10062029
TI  - Lower Bound for the Scale Reduction in Nonlinear Dynamo Process.

PMID- 10062028
TI  - Measuring Implosion Symmetry and Core Conditions on the National Ignition
      Facility.

PMID- 10062030
TI  - Effects of Quantum Fluctuations on Contact Probabilities of a Tunneling Pair in
      Dense Coulomb Liquids.

PMID- 10062031
TI  - Rigidity and Dynamics of Random Spring Networks.

PMID- 10062033
TI  - Experimental Realization of Critical Thermal Fuse Rupture.

PMID- 10062032
TI  - Intrinsic Doping: A New Approach for n-Type Modulation Doping in InP-Based
      Heterostructures.

PMID- 10062034
TI  - Approach to Scaling in Phase-Ordering Kinetics.

PMID- 10062036
TI  - Nature of Layer-by-Layer Freezing in Free-Standing 4O.8 Films.

PMID- 10062035
TI  - Anomalous Behavior of Isotropic Raman Line Shapes near Gas-Liquid Critical
      Points.

PMID- 10062037
TI  - Vortex Excitation in Superfluid 4He: A Diffusion Monte Carlo Study.

PMID- 10062039
TI  - Hybridization versus Local Exchange Interaction in the Kondo Problem: A Two-Band
      Model.

PMID- 10062038
TI  - Photoemission Extended Fine Structure Study of the SiO2/Si(111) Interface.

PMID- 10062040
TI  - Crossover in Electrical Frequency Response through an Insulator-Metal Transition.

PMID- 10062041
TI  - Nonlinear Conductance in Resonant Tunneling.

PMID- 10062042
TI  - Anomalous Spin Scattering Effects in the Badly Metallic Itinerant Ferromagnet
      SrRuO3.

PMID- 10062043
TI  - Dynamical Phases of Driven Vortex Systems.

PMID- 10062044
TI  - Generation of Magnetic Flux by Single Grain Boundaries of YBa2Cu3O7-x.

PMID- 10062045
TI  - Inertial Mass and Viscosity of Tilted Vortex Lines in Layered Superconductors.

PMID- 10062046
TI  - Dynamics of Coupled Quantum Spin Chains.

PMID- 10062047
TI  - Convergent Expansions for Properties of the Heisenberg Model for CaV4 O9.

PMID- 10062048
TI  - Ordering Temperatures and Critical Exponents in Ising Spin Glasses.

PMID- 10062049
TI  - Electron Paramagnetic Resonance Knight Shift in Semimagnetic (Diluted Magnetic)
      Semiconductors.

PMID- 10062050
TI  - Magnetic Behavior of Fe Impurities in Tc and Re, and Its Relevance to the General
      Problem of the Magnetism of Fe in d-Band Metal Hosts.

PMID- 10062051
TI  - Theory for Spin-Polarized Oscillations in Nonlinear Optics due to Quantum Well
      States.

PMID- 10062052
TI  - Terahertz Spin Precession and Coherent Transfer of Angular Momenta in Magnetic
      Quantum Wells.

PMID- 10062054
TI  - First-Order Disorder-to-Order Transition in an Isolated Homopolymer Model.

PMID- 10062053
TI  - Quantum Privacy Amplification and the Security of Quantum Cryptography over Noisy
      Channels.

PMID- 10062055
TI  - Chiral Symmetry Breaking in Crystal Growth: Is Hydrodynamic Convection Relevant?

PMID- 10062056
TI  - Breakdown of Ovchinnikov-Zeldovich Segregation in the A+B-->0 Reaction under Levy
      Mixing.

PMID- 10062057
TI  - Crossover between Spatially Confined Precipitation and Periodic Pattern Formation
      in Reaction Diffusion Systems.

PMID- 10062058
TI  - Comment on the APEX e+e- Experiment.

PMID- 10062059
TI  - Ahmad et al. Reply.

PMID- 10062060
TI  - Comment on "Laser Cooling in the Condensed Phase by Frequency Up-Conversion"

PMID- 10062061
TI  - Rumbles and Clark Reply.

PMID- 10062062
TI  - Comment on "Chaotic Masking Scheme with a Linear Inverse System"

PMID- 10062063
TI  - Oksasoglu and Akgul Reply.

PMID- 10062064
TI  - Comment on "Quantum Monte Carlo Approach to Elementary Excitations of
      Antiferromagnetic Heisenberg Chains"

PMID- 10062065
TI  - Yamamoto Replies.

PMID- 10062067
TI  - Variational Principle for Eigenvalue Problems of Hamiltonian Systems.

PMID- 10062068
TI  - Geometry of Quantum Statistical Inference.

PMID- 10062069
TI  - Simulations of Two-Dimensional Kadomtsev-Petviashvili Soliton Dynamics in Three
      Dimensional Space.

PMID- 10062070
TI  - Construction of the Strong Coupling Expansion for the Ground State Energy of the
      Quartic, Sextic, and Octic Anharmonic Oscillator via a Renormalized Strong
      Coupling Expansion.

PMID- 10062071
TI  - Divergent Signal-to-Noise Ratio and Stochastic Resonance in Monostable Systems.

PMID- 10062072
TI  - Nontrivial Exponent for Simple Diffusion.

PMID- 10062073
TI  - Persistent Spins in the Linear Diffusion Approximation of Phase Ordering and
      Zeros of Stationary Gaussian Processes.

PMID- 10062074
TI  - Gravitational Lensing of Gravitational Waves from Merging Neutron Star Binaries.

PMID- 10062075
TI  - Gravitational Wave Background From Hybrid Topological Defects.

PMID- 10062076
TI  - How Anisotropic is Our Universe?

PMID- 10062077
TI  - Is There a Hot Electroweak Phase Transition at mH >~ mW?

PMID- 10062078
TI  - Off-Shell Supersymmetry versus Hermiticity in Superstrings.

PMID- 10062079
TI  - First Observation of the Tz=-7/2 Nuclei 45Fe and 49Ni.

PMID- 10062081
TI  - Normal Mode Line Shapes for Atoms in Standing-Wave Optical Resonators.

PMID- 10062082
TI  - Vacuum Ultraviolet Spectroscopy of H- in a Heavy Ion Storage Ring: The Region
      near the H(n=2) Threshold.

PMID- 10062080
TI  - Multifragment Production in Reactions of 112Sn+112Sn and 124Sn+124Sn at E/A=40
      MeV.

PMID- 10062083
TI  - Spontaneous Emission from Tunneling Two-Level Atoms.

PMID- 10062084
TI  - Influence of Nearly Resonant Light on the Scattering Length in Low-Temperature
      Atomic Gases.

PMID- 10062085
TI  - Light Absorption in Strongly Irradiated Long Range Polar Electron Transfer
      Systems.

PMID- 10062086
TI  - Three-Body Recombination of Ultracold Atoms to a Weakly Bound s Level.

PMID- 10062088
TI  - Temperature Dependence of Positron Annihilation Rates in Noble Gases.

PMID- 10062087
TI  - Effect of Nuclear Size on the Stopping Power of Ultrarelativistic Heavy Ions.

PMID- 10062089
TI  - Quantum Statistics of the Squeezed Vacuum by Measurement of the Density Matrix in
      the Number State Representation.

PMID- 10062091
TI  - Chaotic Focusing Billiards in Higher Dimensions.

PMID- 10062090
TI  - Equivalence of Synchronization and Control of Chaotic Systems.

PMID- 10062092
TI  - Entropy Production for Open Dynamical Systems.

PMID- 10062093
TI  - Larger Two-Dimensional Photonic Band Gaps.

PMID- 10062094
TI  - Energy and Momentum Growth Rates in Breaking Water Waves.

PMID- 10062095
TI  - Resonant Seeding of Stimulated Brillouin Scattering by Crossing Laser Beams.

PMID- 10062096
TI  - Quantitative Phase Imaging Using Hard X Rays.

PMID- 10062098
TI  - Phase Diagram of Isobutyric Acid and Water in Dilute Silica Gel.

PMID- 10062097
TI  - Thermodynamic Criterion for the Stability of Amorphous Intergranular Films in
      Covalent Materials.

PMID- 10062099
TI  - Properties of 2D 3He on Very Thin 4He Films.

PMID- 10062100
TI  - Surface Alloy Formation by Interdiffusion across a Linear Interface.

PMID- 10062101
TI  - A General Minimum Principle for Correlated Densities in Quantum Many-Particle
      Systems.

PMID- 10062102
TI  - A Novel Direct Method of Fermi Surface Determination Using Constant Initial
      Energy Angle-Scanned Photoemission Spectroscopy.

PMID- 10062103
TI  - Use of the Rigid Band Formalism to Interpret the Relationship between O Chemical
      Potential and Electron Concentration in La 1-xSrxCoO3- delta.

PMID- 10062104
TI  - Conductivity of a Disordered Wigner Crystal.

PMID- 10062105
TI  - Contribution of Surface Resonances to Scanning Tunneling Microscopy Images: (110)
      Surfaces of III-V Semiconductors.

PMID- 10062106
TI  - Synchronization and Chaos Induced by Resonant Tunneling in GaAs/AlAs
      Superlattices.

PMID- 10062107
TI  - Mesoscopic Capacitors: A Statistical Analysis.

PMID- 10062108
TI  - Gauge Fields and Pairing in Double-Layer Composite Fermion Metals.

PMID- 10062109
TI  - Nonzero Fermi Level Density of States for a Disordered d-Wave Superconductor in
      Two Dimensions.

PMID- 10062110
TI  - Vortex Corrections in Antiferromagnetic Spin Fluctuation Theories.

PMID- 10062111
TI  - Spin and Charge Texture around In-Plane Charge Centers in the CuO2 Planes.

PMID- 10062112
TI  - Superconducting Proximity Effect Probed on a Mesoscopic Length Scale.

PMID- 10062113
TI  - Anomalous Proximity Effect in the Nb-BiSb-Nb Junctions.

PMID- 10062115
TI  - A Field Theory for Finite-Dimensional Site-Disordered Spin Systems.

PMID- 10062114
TI  - Magnetic-Field Induced Superconductor-Insulator Transition in the La2-xSrxCuO4
      System.

PMID- 10062116
TI  - The Twelve-Line 1.682 eV Luminescence Center in Diamond and the Vacancy-Silicon
      Complex.

PMID- 10062117
TI  - Quantum Coherence of Continuum States in the Valence Band of GaAs Quantum Wells.

PMID- 10062119
TI  - First Observation of the Molten Globule State of a Single Homopolymer Chain.

PMID- 10062118
TI  - Gas-Surface Dynamics and Profile Evolution during Etching of Silicon.

PMID- 10062120
TI  - Comment on "Classical Chaos as an Environment for Dissipation"

PMID- 10062121
TI  - de Aguiar and de Carvalho Reply.

PMID- 10062123
TI  - Yu et al. Reply.

PMID- 10062122
TI  - Comment on "Tensor Magnetothermal Resistance in YBa2Cu3O7-x via Andreev
      Scattering of Quasiparticles"

PMID- 10062124
TI  - Large Angular Scale Anisotropy in Cosmic Microwave Background Induced by Cosmic
      Strings.

PMID- 10062125
TI  - New Supernova Constraints on Sterile-Neutrino Production.

PMID- 10062126
TI  - Experimental Consequences of a Minimal Messenger Model for Supersymmetry
      Breaking.

PMID- 10062127
TI  - Vacuum Nodes in QCD at theta = pi : Exact Results.

PMID- 10062128
TI  - Q2 Evolution of Chiral-Odd Twist-3 Distributions hL(x,Q2) and e(x,Q2) in Large-Nc
      QCD.

PMID- 10062129
TI  - Evidence for nu -bar micro--> nu -bare Oscillations from the LSND Experiment at
      the Los Alamos Meson Physics Facility.

PMID- 10062131
TI  - Observation of Two-Atom Correlation of an Ultracold Neon Atomic Beam.

PMID- 10062130
TI  - Observation of New Rydberg Series and Resonances in Doubly Excited Helium at
      Ultrahigh Resolution.

PMID- 10062132
TI  - Rydberg atom-Ion Collisions: Quantum Theory of Intrashell Transitions.

PMID- 10062134
TI  - Critical Exponent for Gap Filling at Crisis.

PMID- 10062133
TI  - Simultaneous Ionization and Excitation to the He+ 2(2)P State.

PMID- 10062135
TI  - Longitudinal, Degenerate, and Transversal Parametric Oscillation in
      Photorefractive Media.

PMID- 10062137
TI  - Universal Statistics of Nonlinear Energy Transfer in Turbulent Models.

PMID- 10062136
TI  - Stress Fluctuations for Continuously Sheared Granular Materials.

PMID- 10062138
TI  - Algebraic Tails of Probability Density Functions in the Random-Force-Driven
      Burgers Turbulence.

PMID- 10062139
TI  - Coupled Wakes of Cylinders.

PMID- 10062140
TI  - Spiral-Defect Chaos in Rayleigh-Benard Convection with Small Prandtl Numbers.

PMID- 10062142
TI  - Analytic Three-Dimensional Solutions of the Magnetohydrostatic Equations with
      Twisted Field Lines.

PMID- 10062141
TI  - Tunable X-Ray Generation in a Free-Electron Laser by Intracavity Compton
      Backscattering.

PMID- 10062143
TI  - Dispersion of Plasma Dust Acoustic Waves in the Strong-Coupling Regime.

PMID- 10062144
TI  - Energy Transport in Tokamak Plasmas with Central Current Density Control Using
      Fast Waves.

PMID- 10062146
TI  - Ab initio Molecular Dynamics Simulation of Laser Melting of Silicon.

PMID- 10062145
TI  - Turbulent Fluctuations in TFTR Configurations with Reversed Magnetic Shear.

PMID- 10062147
TI  - Temperature and Pressure Dependence of the Order Parameter Fluctuations,
      Conformational Compressibility, and the Phase Diagram of the PEP-PDMS Diblock
      Copolymer.

PMID- 10062148
TI  - Adsorption-Freezing Transition for Random Heteropolymers near Disordered 2D
      Manifolds due to "Pattern Matching"

PMID- 10062150
TI  - Two-Dimensional Needle Growth of Electrodeposited Ni on Reconstructed Au(111).

PMID- 10062149
TI  - Hydrogen Molecules in Crystalline Silicon Treated with Atomic Hydrogen.

PMID- 10062151
TI  - Roughening Transition of an Amorphous Metal Surface: A Molecular Dynamics Study.

PMID- 10062152
TI  - Density of States in Quasicrystals and Approximants: Tunneling Experiment on Bare
      and Oxidized Surfaces.

PMID- 10062153
TI  - Carrier Dynamics in the Quantum Kinetic Regime.

PMID- 10062154
TI  - Thermodynamics of a Charged Fermion Layer at High rs Values.

PMID- 10062155
TI  - Single Spin Superconductivity.

PMID- 10062156
TI  - Parity-Effected Superconductivity in Ultrasmall Metallic Grains.

PMID- 10062158
TI  - Persistent Metastable States in Vortex Flow at the Peak Effect in NbSe2.

PMID- 10062157
TI  - Anisotropic Magnetic Response in the Superconducting Mixed State of UPt3.

PMID- 10062159
TI  - Anomalous Density of States of a Luttinger Liquid in Contact with a
      Superconductor.

PMID- 10062160
TI  - Ground-State Roughness of the Disordered Substrate and Flux Lines in d=2.

PMID- 10062161
TI  - Surface Instabilities and Plastic Deformation of Vortex Lattices.

PMID- 10062162
TI  - Evolution of the Pseudogap State of High-Tc Superconductors with Doping.

PMID- 10062163
TI  - Effect of Radiation-Induced Oxygen Disorder on the Superconducting Transition
      Temperature in YBa2Cu3O7 Superconductors.

PMID- 10062164
TI  - Direct Measurement of the Conduction Electron Spin-Lattice Relaxation Time T1 in
      Gold.

PMID- 10062165
TI  - Emery-Kivelson Line and Universality of Wilson Ratio of Spin Anisotropic Kondo
      Model.

PMID- 10062166
TI  - Competing Anisotropies in the Ferromagnetic Kondo-Lattice Compound YbNiSn:
      Observation of a Complex Magnetic Ground State under High Pressure.

PMID- 10062167
TI  - Storage of Nuclear Excitation Energy through Magnetic Switching.

PMID- 10062168
TI  - Electronic-Structure Modification and the Adsorption Site of Oxygen on Alkali
      (Cs) Covered Surfaces Studied by Normal Exit Li- Ion Spectroscopy.

PMID- 10062169
TI  - Decoherence Bounds on Quantum Computation with Trapped Ions.

PMID- 10062170
TI  - Spiral Wave Formation in Three-Dimensional Excitable Media.

PMID- 10062171
TI  - Evidence for Newton Black Films between Adhesive Emulsion Droplets.

PMID- 10062172
TI  - The Possibility of Flux Flow Spectroscopy.

PMID- 10062173
TI  - Noise-Induced Coherence in Neural Networks.

PMID- 10062175
TI  - Comment on "Quantum Cryptography with Orthogonal States?"

PMID- 10062174
TI  - Fault-Tolerant Error Correction with Efficient Quantum Codes.

PMID- 10062178
TI  - Nonlinear Coherent Multiwave Modes: Universal Integrals of Motion and Effective
      Hamiltonian.

PMID- 10062176
TI  - Goldenberg and Vaidman Reply.

PMID- 10062179
TI  - Reduced Dynamics with Initial Correlations, and Time-Dependent Environment and
      Hamiltonians.

PMID- 10062180
TI  - Binary Mixtures of Bose Condensates of Alkali Atoms.

PMID- 10062181
TI  - Expansion for the Moments of a Nonlinear Stochastic Model.

PMID- 10062183
TI  - Black Hole Entropy from Loop Quantum Gravity.

PMID- 10062182
TI  - The Boundary Value Problem for the Stationary and Axisymmetric Einstein Equations
      is Generically Solvable.

PMID- 10062184
TI  - New Mechanism for Leptogenesis.

PMID- 10062185
TI  - Summing up Dirichlet Instantons.

PMID- 10062186
TI  - Left-Handed Neutrino Disappearance Probe of Neutrino Mass and Character.

PMID- 10062187
TI  - Search for Anomalous WW and WZ Production in pp-bar Collisions at sqrt s=1.8 TeV.

PMID- 10062189
TI  - Nuclear Shell Model by the Quantum Monte Carlo Diagonalization Method.

PMID- 10062190
TI  - Evidence for Naturally Occurring Electron Capture of 123Te.

PMID- 10062188
TI  - Measurement of the W Boson Mass.

PMID- 10062191
TI  - Correlation and Negative Continuum Effects for the Relativistic M1 Transition in
      Two-Electron Ions using the Multiconfiguration Dirac-Fock Method.

PMID- 10062193
TI  - Low-Velocity Intense Source of Atoms from a Magneto-optical Trap.

PMID- 10062192
TI  - Dipole-Dipole Broadened Line Shape in a Partially Excited Dense Atomic Gas.

PMID- 10062194
TI  - Photoelectron-Photofragment Angular Correlation and Energy Partitioning in
      Dissociative Photodetachment.

PMID- 10062195
TI  - Velocity and Charge State Dependences of Molecular Dissociation Induced by Slow
      Multicharged Ions.

PMID- 10062196
TI  - Multi-keV Electron Generation in the Interaction of Intense Laser Pulses with Xe
      Clusters.

PMID- 10062197
TI  - Intense Field-Matter Interactions: Multiple Ionization of Clusters.

PMID- 10062198
TI  - Near-Field Optical Holography.

PMID- 10062199
TI  - Nonlinear Interaction of Light with Transversely Moving Medium.

PMID- 10062201
TI  - Interface Roughening in a Hydrodynamic Lattice-Gas Model with Surfactant.

PMID- 10062200
TI  - Time- and Space-Resolved Optical Probing of Femtosecond-Laser-Driven Shock Waves
      in Aluminum.

PMID- 10062202
TI  - Interfacial Control of Reaction Kinetics in Oxides.

PMID- 10062204
TI  - TiC(001) Surface Relaxation.

PMID- 10062203
TI  - Structure and Stability of a High-Coverage (1 x 1) Oxygen Phase on Ru(0001).

PMID- 10062205
TI  - Congruent Phase Transition at a Twist Boundary Induced by Solute Segregation.

PMID- 10062207
TI  - Critical Role of Crystalline Anisotropy in the Stability of Cellular Array
      Structures in Directional Solidification.

PMID- 10062206
TI  - Local Structure of the Amorphous Precursor to Ba-Hexaferrite Thin Films: An
      Anisotropic Octahedral Fe-O Glass Network.

PMID- 10062208
TI  - Kosterlitz-Thouless Transition and Short Range Spatial Correlations in an
      Extended Hubbard Model.

PMID- 10062210
TI  - Electron Tunneling Study of Coulomb Correlations across the Metal-Insulator
      Transition in Si:B.

PMID- 10062209
TI  - Electronic Transport Processes in Heavily Doped Uncompensated and Compensated
      Silicon as Probed by the Thermoelectric Power.

PMID- 10062211
TI  - Topological Dislocations and Mixed State of Charge Density Waves.

PMID- 10062212
TI  - Identification of the Native Vacancy Defects in Both Sublattices of ZnSx Se1-x by
      Positron Annihilation.

PMID- 10062213
TI  - Point-Contact Study of Fast and Slow Two-Level Fluctuators in Metallic Glasses.

PMID- 10062215
TI  - Spin Splitting of an Au(111) Surface State Band Observed with Angle Resolved
      Photoelectron Spectroscopy.

PMID- 10062214
TI  - Temperature Dependence of the Exchange Splitting of the Surface State on
      Gd(0001): Evidence against Spin-Mixing Behavior.

PMID- 10062216
TI  - Mutual Exclusion Statistics between Quasiparticles in the Fractional Quantum Hall
      Effect.

PMID- 10062217
TI  - Trap-Limited Electronic Transport in Assemblies of Nanometer-Size TiO2 Particles.

PMID- 10062218
TI  - NMR in Copper-Oxide Metals.

PMID- 10062219
TI  - Thermal Activation above a Dissipation Barrier: Switching of a Small Josephson
      Junction.

PMID- 10062221
TI  - Phase Transitions in Staggered Spin Ladders.

PMID- 10062220
TI  - Temperature and Spin Dependent Correlation Length of the Quantum Heisenberg
      Antiferromagnet on the Square Lattice.

PMID- 10062222
TI  - New Mechanism of f-f Exchange Interactions Controlled by Fermi Level Position.

PMID- 10062223
TI  - Thermodynamic measurements of magnetic ordering in antiferromagnetic
      superlattices.

PMID- 10062224
TI  - Quantum Well States and Short Period Oscillations of the Density of States at the
      Fermi Level in Cu Films Grown on fcc Co(100).

PMID- 10062225
TI  - High-Frequency Electron Paramagnetic Resonance of Tm3+ Ions in Lanthanum and
      Thulium Ethylsulphate Single Crystals.

PMID- 10062226
TI  - Single-Electron Subpicosecond Coherent Dynamics in KBr F Centers.

PMID- 10062227
TI  - Acoustic Energy Storage in Single Bubble Sonoluminescence.

PMID- 10062229
TI  - Nonphotochemical, Polarization-Dependent, Laser-Induced Nucleation in
      Supersaturated Aqueous Urea Solutions.

PMID- 10062228
TI  - Femtosecond Spectroscopic Signatures of Electronic Correlations in Conjugated
      Polyenes and Semiconductor Nanostructures.

PMID- 10062230
TI  - Anomalous Phase Fluctuations Accompanying the Crystallographic Phase Transition
      in UNi2Sn.

PMID- 10062232
TI  - Squeezing of Oil-Swollen Surfactant Bilayers by a Membrane Protein.

PMID- 10062231
TI  - Emulsification in Viscoelastic Media.

PMID- 10062233
TI  - Quantum Phase Diffusion of a Bose-Einstein Condensate.

PMID- 10062235
TI  - Statistical Hair on Black Holes.

PMID- 10062234
TI  - Stability of Quantum Electrodynamics with Nonrelativistic Matter.

PMID- 10062236
TI  - Do About Half the Top Quarks at Fermilab Come from Gluino Decays?

PMID- 10062237
TI  - Multilepton Signal for Supersymmetric Particles in the Fermilab Tevatron Data?

PMID- 10062238
TI  - Search for the Production of Pionium Atoms near Threshold.

PMID- 10062239
TI  - Dynamical Fragment Production as a Mode of Energy Dissipation in Heavy-Ion
      Reactions.

PMID- 10062240
TI  - Wave Packet Isotope Separation.

PMID- 10062241
TI  - Insertion of Be Atoms in C60 Fullerene Cages: Be@ C60.

PMID- 10062242
TI  - Cold Metal Clusters: Helium Droplets as a Nanoscale Cryostat.

PMID- 10062244
TI  - Holographic Laser Oscillator Which Adaptively Corrects for Polarization and Phase
      Distortions.

PMID- 10062243
TI  - Cage Destruction in Metal-Fullerene Clusters.

PMID- 10062245
TI  - New Amplitude Equations for Thin Elastic Rods.

PMID- 10062246
TI  - Viscous Lengths in Hydrodynamic Turbulence are Anomalous Scaling Functions.

PMID- 10062247
TI  - The Rosseland Mean Opacity of a Mixture of Gold and Gadolinium at High
      Temperatures.

PMID- 10062248
TI  - Nonlinear Saturation of an Electrostatic Wave: Mobile Ions Modify Trapping
      Scaling.

PMID- 10062249
TI  - Off-Axis Sawteeth and Double-Tearing Reconnectionin Reversed Magnetic Shear
      Plasmas in TFTR.

PMID- 10062250
TI  - Charge-Exchange Atoms and Ion Source Divergence in a 20 TW Applied-B Ion Diode.

PMID- 10062251
TI  - Ginzburg Criterion for Coulombic Criticality.

PMID- 10062253
TI  - Correlation between Free Volume and Ionic Conductivity in Fast Ion Conducting
      Glasses.

PMID- 10062252
TI  - Freezing Transition of Compact Polyampholytes.

PMID- 10062254
TI  - First Principles Study of a New Large-Gap Nonoporous Silicon Crystal: Hex-Si40.

PMID- 10062255
TI  - Probabilistic Fragmentation and Effective Power Law.

PMID- 10062256
TI  - Frozen Disorder in a Driven System.

PMID- 10062257
TI  - bcc Symmetry in the Crystal-Melt Interface of Lennard-Jones Fluids Examined
      through Density Functional Theory.

PMID- 10062258
TI  - Unconventional Quasiparticle Lifetime in Graphite.

PMID- 10062259
TI  - Anderson Transition in Three-Dimensional Disordered Systems with Symplectic
      Symmetry.

PMID- 10062260
TI  - Optical Josephson Effect in Semiconductors.

PMID- 10062262
TI  - Schrodinger's Equation as a Model Approach to Short Time-Scale Quantum Kinetics
      in a Semiconductor.

PMID- 10062261
TI  - Mechanisms of Impurity Deactivation in GaAs during Reactive Ion Etching.

PMID- 10062263
TI  - Low Energy Properties of M-State Tunneling Systems in Metals: New Candidates for
      Non-Fermi-Liquid Systems.

PMID- 10062265
TI  - Giant Radiation Linewidth of Multifluxon States in Long Josephson Junctions.

PMID- 10062264
TI  - Shell Filling and Spin Effects in a Few Electron Quantum Dot.

PMID- 10062266
TI  - Gap States in Dilute Magnetic Alloy Superconductors.

PMID- 10062268
TI  - Exact Single Spin Flip for the Hubbard Model in d=

PMID- 10062267
TI  - Vortex Plastic Motion in Twinned Superconductors.

PMID- 10062269
TI  - Spin Gaps in a Frustrated Heisenberg Model for CaV4O9.

PMID- 10062270
TI  - Possible Correlated-Electron Behavior from Quadrupolar Fluctuations in PrInAg2.

PMID- 10062271
TI  - Order-Parameter Distribution Function of Finite O(n) Symmetric Systems.

PMID- 10062272
TI  - Near-Surface Long-Range Order at the Ordinary Transition.

PMID- 10062273
TI  - Quantum Spin Excitations in the Spin-Peierls System CuGeO3.

PMID- 10062274
TI  - Magnetization Reversal in Ultrathin Films with Monolayer-Scale Surface Roughness.

PMID- 10062275
TI  - Nonequilibrium Dynamics in a Quasi-Two-Dimensional Electron Plasma after
      Ultrafast Intersubband Excitation.

PMID- 10062276
TI  - Coherent THz Phonons Driven by Light Pulses and the Sb Problem: What is the
      Mechanism?

PMID- 10062277
TI  - Inelastic X-Ray Scattering Study of Solid and Liquid Li and Na.

PMID- 10062278
TI  - Correlated Prediction of the Photoelectron Spectrum of Polyethylene: Explanation
      of XPS and UPS Measurements.

PMID- 10062279
TI  - Dynamic Properties of Semidilute Solutions at the Theta Point.

PMID- 10062281
TI  - Cell Dynamics of Model Proteins.

PMID- 10062280
TI  - Grain Growth and Defect Annihilation in Block Copolymers.

PMID- 10062282
TI  - Fluid Vesicles in Shear Flow.

PMID- 10062284
TI  - Comment on "Singlet Semiconductor to Ferromagnetic Metal Transition in FeSi"

PMID- 10062283
TI  - Scaling Laws for Fracture of Heterogeneous Materials and Rock.

PMID- 10062285
TI  - Quantum Monte Carlo Calculations for a Large Number of Bosons in a Harmonic Trap.

PMID- 10062286
TI  - Absence of Self-Averaging and Universal Fluctuations in Random Systems near
      Critical Points.

PMID- 10062287
TI  - Global Persistence Exponent for Nonequilibrium Critical Dynamics.

PMID- 10062288
TI  - Limits on Models of the Ultrahigh Energy Cosmic Rays Based on Topological
      Defects.

PMID- 10062290
TI  - Preheating, Supersymmetry Breaking, and Baryogenesis.

PMID- 10062289
TI  - Solving the Crisis in Big-Bang Nucleosynthesis by the Radiative Decay of an
      Exotic Particle.

PMID- 10062291
TI  - Probability of a Solution to the Solar Neutrino Problem within the Minimal
      Standard Model.

PMID- 10062292
TI  - Continuum Study of Deconfinement at Finite Temperature.

PMID- 10062293
TI  - Anomalous U(1) as a Mediator of Supersymmetry Breaking.

PMID- 10062294
TI  - Triple Pseudoscalar Decay Mode of the Z Boson.

PMID- 10062295
TI  - Percolation Approach to Quark-Gluon Plasma and J/ psi Suppression.

PMID- 10062296
TI  - Mass Dependence of Directed Collective Flow.

PMID- 10062297
TI  - Yrast Excitations around Doubly Magic 132Sn from Fission Product gamma -ray
      Studies.

PMID- 10062298
TI  - Selective Nuclear Transparency Induced by Chaotic Scattering.

PMID- 10062300
TI  - The Photodetachment Microscope.

PMID- 10062299
TI  - Observation of Doubly Excited States in Li-

PMID- 10062301
TI  - Multiply Charged Negative Ions of Hydrogen Induced by Superintense Laser Fields.

PMID- 10062302
TI  - Excitation of Small Quantum Systems by High-Frequency Fields.

PMID- 10062303
TI  - Doubly Differential Final-State Momentum Distributions of the Ionization Products
      in Collision of Bare Ions with Hydrogen.

PMID- 10062304
TI  - Vibrationally Resolved Electron Attachment to Oxygen Clusters.

PMID- 10062305
TI  - Observation of Optical Soliton Photon-Number Squeezing.

PMID- 10062307
TI  - Observation of Pulse Splitting in Nonlinear Dispersive Media.

PMID- 10062306
TI  - Nonlinear Control of Remote Unstable States in a Liquid Bridge Convection
      Experiment.

PMID- 10062308
TI  - High Transmission through Sharp Bends in Photonic Crystal Waveguides.

PMID- 10062309
TI  - Observation of Stability Boundaries in the Parameter Space of Single Bubble
      Sonoluminescence.

PMID- 10062311
TI  - Scaling of Low-Order Structure Functions in Homogeneous Turbulence.

PMID- 10062310
TI  - Scale Distributions and Fractal Dimensions in Turbulence.

PMID- 10062312
TI  - Anomalous Temperature Reduction of Electron-Cooled Heavy Ion Beams in the Storage
      Ring ESR.

PMID- 10062313
TI  - Detailed Characterization of Electron Plasma Waves Produced by Stimulated Raman
      Scattering.

PMID- 10062314
TI  - Observation of Nonclassical Radial Current Diffusion in a Fully Bootstrap Current
      Driven Tokamak.

PMID- 10062315
TI  - Direct Measurement of X-Ray Drive from Surrogate Targets in Nova Hohlraums.

PMID- 10062316
TI  - Efficient Co-Generation of Seventh-Harmonic Radiation in Cyclotron Autoresonance
      Acceleration.

PMID- 10062317
TI  - Direct Experimental Evidence of the Relationship between Intermediate-Range Order
      in Topologically Disordered Matter and Discernible Features in the Static
      Structure Factor.

PMID- 10062318
TI  - Evidence for a Cluster-Based Structure of AIPdMn Single Quasicrystals.

PMID- 10062319
TI  - Scattering Investigation of Acoustic Localization in Fused Silica.

PMID- 10062320
TI  - Evidence of High Frequency Propagating Modes in Vitreous Silica.

PMID- 10062322
TI  - Nonuniversal Scaling Behavior of Barkhausen Noise.

PMID- 10062321
TI  - Anharmonic Decay of Vibrational States in Amorphous Silicon.

PMID- 10062323
TI  - Early Stages of Nucleation and Growth in a Polymer Blend.

PMID- 10062324
TI  - Surface Structure of 1 x 2 Reconstructed TiO2(110) Studied Using Electron
      Stimulated Desorption Ion Angular Distribution.

PMID- 10062325
TI  - Self-Similar Barkhausen Noise in Magnetic Domain Wall Motion.

PMID- 10062326
TI  - Pressure Dependence (10(-10)-700 Torr) of the Vibrational Spectra of Adsorbed CO
      on Pt(111) Studied by Sum Frequency Generation.

PMID- 10062328
TI  - Generalized Gradient Approximation Made Simple.

PMID- 10062327
TI  - Growth Processes in Si/Si(111) Epitaxy Observed by Scanning Tunneling Microscopy
      during Epitaxy.

PMID- 10062329
TI  - Dynamics-Induced Surface Metallization of Si(100).

PMID- 10062330
TI  - Photoluminescence Spectroscopy of Single CdSe Nanocrystallite Quantum Dots.

PMID- 10062331
TI  - Imaging of Surface Plasmon Scattering by Lithographically Created Individual
      Surface Defects.

PMID- 10062332
TI  - Giant Quantum Oscillations of Acoustoelectric Effect in Nanostructures.

PMID- 10062333
TI  - Fractal Conductance Fluctuations in Gold Nanowires.

PMID- 10062335
TI  - Evidence of Momentum Conservation at a Nonepitaxial Metal/Semiconductor Interface
      using Ballistic Electron Emission Microscopy.

PMID- 10062334
TI  - Charging in Solitary, Voltage Biased Tunnel Junctions.

PMID- 10062336
TI  - Friedel Transition in Layered Superconductors.

PMID- 10062338
TI  - Dynamic Measurement of Percolative Critical Exponents in Disordered Josephson
      Junction Arrays.

PMID- 10062337
TI  - Plasma Resonance and Remaining Josephson Coupling in the "Decoupled Vortex Liquid
      Phase" in Layered Superconductors.

PMID- 10062339
TI  - Theory of Thermal Conductivity in YBa2Cu3O7- delta.

PMID- 10062340
TI  - ab-Plane Anisotropy of Transport Properties in Unidirectionally Twinned YBa2Cu3O7
      delta Films.

PMID- 10062341
TI  - On the Magnetic Interactions in Metal-Be13 Compounds.

PMID- 10062342
TI  - Evidence for Ferromagnetic Order at the FeO(111) Surface.

PMID- 10062343
TI  - Element Specific Magnetization of Buried Interfaces Probed by Diffuse X-Ray
      Resonant Magnetic Scattering.

PMID- 10062345
TI  - Adsorption and Dissociation of O2 on Ag(110).

PMID- 10062344
TI  - Symmetry Analysis of the Nonlinear Optical Response: Second Harmonic Generation
      at Surfaces of Antiferromagnets.

PMID- 10062346
TI  - Structure of Polyelectrolyte Solutions.

PMID- 10062349
TI  - Ising Model with a Boundary Magnetic Field on a Random Surface.

PMID- 10062348
TI  - Asymptotic Behavior of N-Soliton Trains of the Nonlinear Schrodinger Equation.

PMID- 10062350
TI  - Real-Time History of the Cosmological Electroweak Phase Transition.

PMID- 10062351
TI  - Nonfactorizable QCD and Electroweak Corrections to the Hadronic Z Boson Decay
      Rate.

PMID- 10062353
TI  - Relativistic Hartree-Bogoliubov Description of the Neutron Halo in 11Li.

PMID- 10062352
TI  - Structure Analysis of the fJ(1710) in the Radiative Decay J/ psi --> gamma K+K-

PMID- 10062354
TI  - New Region of Deformation: The Neutron-Rich Sulfur Isotopes.

PMID- 10062355
TI  - Demonstration of a Two Species Noble Gas Maser.

PMID- 10062356
TI  - Experimental Evidence for Circular Dichroism in the Double Photoionization of
      Helium.

PMID- 10062357
TI  - Single Molecule Dynamics Studied by Polarization Modulation.

PMID- 10062358
TI  - Observation of Negative Ion Resonances in Amorphous Ice via Low-Energy (5-40 eV)
      Electron-Stimulated Production of Molecular Hydrogen.

PMID- 10062359
TI  - Energy-Loss-Straggling Experiments with Relativistic Heavy Ions in Solids.

PMID- 10062360
TI  - Radiative Cooling of C60.

PMID- 10062361
TI  - Ultranarrow Spectral Lines via Quantum Interference.

PMID- 10062362
TI  - Generic Structure of Multilevel Quantum Beats.

PMID- 10062363
TI  - Universal Critical Behavior in Two-Dimensional Coupled Map Lattices.

PMID- 10062364
TI  - Stabilization, Selection, and Tracking of Unstable Patterns by Fourier Space
      Techniques.

PMID- 10062366
TI  - Global Instability in Fully Nonlinear Systems.

PMID- 10062365
TI  - Investigation of Black-Gray Soliton Interaction.

PMID- 10062367
TI  - Correlation of Charged Fluids Separated by a Wall.

PMID- 10062368
TI  - Polarization Effects, Network Dynamics, and the Infrared Spectrum of Amorphous
      SiO2.

PMID- 10062370
TI  - Observation of Moving Dislocation Kinks and Unpinning.

PMID- 10062369
TI  - Incommensurate Intermodulation of an Organic Intergrowth Compound Observed by
      Neutron Scattering.

PMID- 10062371
TI  - Is the Fast Process at the Glass Transition Mainly due to Long Wavelength
      Excitations?

PMID- 10062372
TI  - Critical Behavior of the Restricted Primitive Model.

PMID- 10062373
TI  - High-Resolution Measurements of Rotons in 4He.

PMID- 10062374
TI  - Structural Transition in Large-Lattice-Mismatch Heteroepitaxy.

PMID- 10062375
TI  - Numerical Simulation of Three-Dimensional Dendritic Growth.

PMID- 10062376
TI  - Observation of Spin-Charge Separation in One-Dimensional SrCuO2.

PMID- 10062378
TI  - Generation and Relaxation of Coherent Majority Plasmons.

PMID- 10062377
TI  - Hopping Conduction and Metal-Insulator Transition in Isotopically Enriched
      Neutron-Transmutation-Doped 70Ge:Ga.

PMID- 10062379
TI  - Electronic Structure Calculations for YBa2Cu3O7 within the Slave Boson Formalism.

PMID- 10062381
TI  - Star-Shaped Local Density of States around Vortices in a Type-II Superconductor.

PMID- 10062380
TI  - Low-Temperature Anomaly in the Josephson Critical Current of Junctions in d-Wave
      Superconductors.

PMID- 10062382
TI  - Dynamic Matching of Vortex Lattice in Superconducting Multilayers.

PMID- 10062383
TI  - Energy Gap in Superconducting Fullerides: Optical and Tunneling Studies.

PMID- 10062384
TI  - Magnetic Raman Scattering from 1D Antiferromagnets.

PMID- 10062385
TI  - Pseudogap and Charge Dynamics in CuO2 Planes in YBCO.

PMID- 10062386
TI  - Nonequilibrium Critical Dynamics of a Three Species Monomer-Monomer Model.

PMID- 10062387
TI  - Stochastic Resonance in a Neuronal Network from Mammalian Brain.

PMID- 10062388
TI  - Propulsion of Microorganisms by Surface Distortions.

PMID- 10062389
TI  - Comment on "Phonons in Glasses: Numerical Simulations and Phenomenological
      Theory"

PMID- 10062390
TI  - Caprion, Jund, and Jullien Reply.

PMID- 10062393
TI  - Perturbative Expansion for Coherence Loss.

PMID- 10062394
TI  - Transformation of the Bethe Equations for Finite Cycles into Secular Polynomials
      in Energy.

PMID- 10062395
TI  - Does Chaotic Mixing Facilitate Omega <1 Inflation?

PMID- 10062396
TI  - Classical Decay of the Inflaton.

PMID- 10062397
TI  - New Interpretation of the Observed Heavy Baryons.

PMID- 10062398
TI  - Charm Correlation as a Diagnostic Probe of Quark Matter.

PMID- 10062399
TI  - Jet Quenching in the Direction Opposite to a Tagged Photon in High-Energy Heavy
      Ion Collisions.

PMID- 10062401
TI  - Decay Out of the Yrast and Excited Highly Deformed Bands in the Even-Even Nucleus
      134Nd.

PMID- 10062400
TI  - Dynamics of the Multifragmentation of 1A GeV Gold on Carbon.

PMID- 10062402
TI  - Diagnostic Value of Photofragment Anisotropy Measurements: Predissociation
      Mechanisms of the e 1 Pi u State of N2.

PMID- 10062403
TI  - Ab Initio Photoabsorption Spectra and Structures of Small Semiconductor and Metal
      Clusters.

PMID- 10062404
TI  - Experimental Evidence for the Entropy Effect in Coulombic Cluster Fission.

PMID- 10062406
TI  - Invariant Measures as Lagrangian Variables: Their Application to Time Series
      Analysis.

PMID- 10062405
TI  - Two-Photon Spectroscopy of Trapped Atomic Hydrogen.

PMID- 10062407
TI  - Quantum Chaos and the Limits of Semiclassical Prediction.

PMID- 10062408
TI  - Winding Number Instability in the Phase-Turbulence Regime of the Complex Ginzburg
      Landau Equation.

PMID- 10062409
TI  - Interacting Self-Guided Beams viewed as Particles: Lorentz Force Derivation.

PMID- 10062411
TI  - Tribology of Sliding Elastic Media.

PMID- 10062410
TI  - Force Distributions in Dense Two-Dimensional Granular Systems.

PMID- 10062412
TI  - Short-Wave Limit of Hydrodynamics: A Soluble Example.

PMID- 10062413
TI  - Taylor Vortices in Wide Spherical Shells.

PMID- 10062414
TI  - Experimental Investigation of the Sedimentation of a Dilute Fiber Suspension.

PMID- 10062415
TI  - Experimental Observation of rf Driven Plasma Flow in the Phaedrus-T Tokamak.

PMID- 10062416
TI  - Temporally Resolved Measurement of Electron Densities (>10(23) cm-3) with High
      Harmonics.

PMID- 10062418
TI  - Force-Extension Relation and Plateau Modulus for Wormlike Chains.

PMID- 10062417
TI  - Liquid-Crystalline Phases of Semiflexible Diblock Copolymer Melts.

PMID- 10062419
TI  - Surface-Mediated Disorder in Aligned Liquid Crystal Films Caused by Collisions
      with He.

PMID- 10062420
TI  - Pressure-Induced Crossover from Long- to Short-Range Order in Compositionally
      Disordered Soft Mode Ferroelectrics.

PMID- 10062421
TI  - Fast Dynamics of Glass-Forming Glycerol Studied by Dielectric Spectroscopy.

PMID- 10062422
TI  - Observation of Ferromagnetic Ordering in hcp 3He.

PMID- 10062423
TI  - Measurement of Interface-Induced Optical Anisotropies of a Semiconductor
      Heterostructure: ZnSe/GaAs(100).

PMID- 10062424
TI  - Striped Phase and Temperature Dependent Step Shape Transition on Highly B-Doped
      Si(001)-(2 x 1) Surfaces.

PMID- 10062425
TI  - Exchange-Coupled Spin-Fluctuation Theory: Application to Fe, Co, and Ni.

PMID- 10062426
TI  - Quantum Gap Solitons and Many-Polariton-Atom Bound States in Dispersive Medium
      and Photonic Band Gap.

PMID- 10062428
TI  - Valence-Electron Resonances in Alkali-Metal Overlayers Observed via Photoemission
      Line-Shape Changes.

PMID- 10062427
TI  - Zeeman Effect in Parabolic Quantum Dots.

PMID- 10062429
TI  - Coulomb Blockade as a Noninvasive Probe of Local Density of States.

PMID- 10062430
TI  - Shell Structure and Electronic Excitations of Quantum Dots in a Magnetic Field
      Probed by Inelastic Light Scattering.

PMID- 10062431
TI  - Electron-Phonon Interactions on a Single-Branch Quantum Hall Edge.

PMID- 10062432
TI  - Logarithmic Temperature Dependence of Conductivity at Half Filled Landau Level.

PMID- 10062433
TI  - Sign Reversals of the Quantum Hall Effect in Quasi-1D Conductors.

PMID- 10062434
TI  - Incommensurate One-Dimensional Fluctuations in YBa2 Cu3O6.93.

PMID- 10062435
TI  - Bulk Superconductivity at 10 K in the Layered Compounds Y2C 2I2 and Y2C2Br2.

PMID- 10062436
TI  - Mixed Phase of a Longitudinal Ferromagnetism and a Transverse Antiferromagnetism
      in a Site-Random Heisenberg Model.

PMID- 10062437
TI  - Effect of Chiral Domain Walls on the Specific Heat of Gd(hfac)3NITR
      (R=Ethyl,Isopropyl,Methyl,Phenyl) Molecular Magnetic Chains.

PMID- 10062438
TI  - Stabilization of Long-Range Magnetic Order in 2D Easy-Plane Antiferromagnets.

PMID- 10062439
TI  - Two Mechanisms and a Scaling Relation for Dynamics in Ferrofluids.

PMID- 10062440
TI  - Surface Spin Disorder in NiFe2O4 Nanoparticles.

PMID- 10062441
TI  - Deviations from Drude Response in Low-Dimensional Metals: Electrodynamics of the
      Metallic State of (TMTSF)2PF6.

PMID- 10062442
TI  - Comment on "Anomalous Spin Diffusion in a Two-Dimensional Percolating Ising
      Antiferromagnet"

PMID- 10062443
TI  - Ikeda, Itoh, and Adams Reply.

PMID- 10062444
TI  - Comment on "Six-Dimensional Quantum Dynamics of Adsorption and Desorption of H2
      at Pd(100): Steering and Steric Effects"

PMID- 10062445
TI  - Gross and Scheffler Reply.

PMID- 10062446
TI  - Comment on "Suppression of Molecular Interactions in Periodic Dielectric
      Structures"

PMID- 10062448
TI  - Comment on "Collisional Deexcitation at Ion-Bombarded Surfaces"

PMID- 10062447
TI  - Kurizki, Kofman, and Genack Reply.

PMID- 10062449
TI  - Fine et al. Reply.

PMID- 10062452
TI  - Multiple-Scale Analysis of the Quantum Anharmonic Oscillator.

PMID- 10062451
TI  - Asymptotic Conservation Laws in Classical Field Theory.

PMID- 10062454
TI  - Quantum Proximity Resonances.

PMID- 10062453
TI  - Ground State Wave Function of a Schrodinger-Like Equation in a Time Periodic
      Potential.

PMID- 10062455
TI  - Global Minimum Principle for Schrodinger Equation Inverse Scattering.

PMID- 10062457
TI  - Gravitational Waves and Pulsating Stars: What Can We Learn from Future
      Observations?

PMID- 10062456
TI  - Traversable Wormholes in Geometries of Charged Shells.

PMID- 10062458
TI  - A Causal Source Which Mimics Inflation.

PMID- 10062459
TI  - Signals for Double Parton Scattering at the Fermilab Tevatron.

PMID- 10062460
TI  - Analysis of the Z0 Resonant Amplitude in General R xi Gauges.

PMID- 10062461
TI  - Two-Electron Dissociative Ionization of H2 and D2 in Infrared Laser Fields.

PMID- 10062462
TI  - Calculated Electron Dynamics in a Strong Electric Field.

PMID- 10062463
TI  - Parametric Variation of Chaotic Eigenstates and Phase Space Localization.

PMID- 10062464
TI  - Synchronization of Spatiotemporal Chaos and Its Application to Spread-Spectrum
      Communication.

PMID- 10062465
TI  - Spontaneous Wave Pattern Formation in Vibrated Granular Materials.

PMID- 10062466
TI  - Hydrodynamic Irreversibility in Creeping Flow.

PMID- 10062467
TI  - Mixing and Thermal Equilibrium in the Dynamical Relaxation of a Vortex Ring.

PMID- 10062468
TI  - Streamer Propagation as a Pattern Formation Problem: Planar Fronts.

PMID- 10062469
TI  - X-Ray Based Subpicosecond Electron Bunch Characterization Using 90 degrees
      Thomson Scattering.

PMID- 10062470
TI  - Guiding of High Intensity Laser Pulses in Straight and Curved Plasma Channel
      Experiments.

PMID- 10062471
TI  - Improved Particle Confinement Mode in the H-1 Heliac Plasma.

PMID- 10062473
TI  - Metastability and Crystallization in Hard-Sphere Systems.

PMID- 10062472
TI  - Localization in Two Dimensions, Gaussian Field Theories, and Multifractality.

PMID- 10062474
TI  - Width of the Darwin Table for Forbidden Reflections.

PMID- 10062476
TI  - Medium-Range Order in Permanently Densified SiO2 and GeO2 Glass.

PMID- 10062475
TI  - Epitaxial Growth of SiO2 Produced in Silicon by Oxygen Ion Implantation.

PMID- 10062477
TI  - Identification of Grown-In Efficient Nonradiative Recombination Centers in
      Molecular Beam Epitaxial Silicon.

PMID- 10062478
TI  - Nematic-Smectic Transition of Semiflexible Chains.

PMID- 10062479
TI  - Spatially Extended Avalanches in a Hysteretic Capillary Condensation System:
      Superfluid 4He in Nuclepore.

PMID- 10062480
TI  - Imaging the Dimers in Si(111)-(7 x 7).

PMID- 10062481
TI  - Dynamics of the C-O Stretch Overtone Vibration of CO/Ru(001).

PMID- 10062482
TI  - Interacting Arrays of Lines and Steps in Random Media.

PMID- 10062483
TI  - Novel Analytic Calculation of Electron Gas Properties.

PMID- 10062484
TI  - Coherence and Localization in 2D Luttinger Liquids.

PMID- 10062485
TI  - Acoustic Edge Modes of the Degenerate Two-Dimensional Electron Gas Studied by
      Time-Resolved Magnetotransport Measurements.

PMID- 10062486
TI  - Nonlocal Photorefractive Screening from Hot Electron Velocity Saturation in
      Semiconductors.

PMID- 10062488
TI  - One-Dimensional Localization of Quantum Vortices in Disordered Josephson Junction
      Arrays.

PMID- 10062487
TI  - Transport Properties of a YBa2Cu4O8 Crystal under High Pressure.

PMID- 10062489
TI  - Magnetic Hyperfine Fields at Se Adatoms on Ni Surfaces.

PMID- 10062490
TI  - Electron Capture Processes on Oxidized Surfaces: H- Formation on Mg/O2 and Al/O2.

PMID- 10062491
TI  - Low-Energy Electronic Structure of the Kondo Insulator YbB12.

PMID- 10062493
TI  - Flyvbjerg Replies.

PMID- 10062492
TI  - Comment on "Simplest Possible Self-Organized Critical System"

PMID- 10062494
TI  - Collapse of Randomly Linked Polymers.

PMID- 10062495
TI  - Comment on "Internal Constraints Induce Localization in an Isolated Polymer
      Molecule"

PMID- 10062496
TI  - Bryngelson and Thirumalai Reply.

PMID- 10062500
TI  - Experimental Determination of the Motional Quantum State of a Trapped Atom.

PMID- 10062501
TI  - 3He Transport in the Sun and the Solar Neutrino Problem.

PMID- 10062502
TI  - Grand-Unified-Theory Baryogenesis after Preheating.

PMID- 10062503
TI  - Nonspreading Wave Packets for Rydberg Electrons in Rotating Molecules with
      Electric Dipole Moments.

PMID- 10062504
TI  - Variation of Cross-Section Enhancement in Decay Spectra of CO under Resonant
      Raman Conditions.

PMID- 10062505
TI  - Double Rydberg States Formed in Stabilized Triple Electron Capture.

PMID- 10062506
TI  - Strong Induced-Dipole-Field Oscillations of the dt micro System above the t
      micro(n=2) Threshold.

PMID- 10062507
TI  - Resonance of Quantum Noise in an Unstable Cavity Laser.

PMID- 10062508
TI  - Why do Chaotic Orbits Converge under a Random Velocity Reset?

PMID- 10062509
TI  - Chaotic Properties of Quantum Many-Body Systems in the Thermodynamic Limit.

PMID- 10062510
TI  - Efficient Nonlinear Frequency Conversion with Maximal Atomic Coherence.

PMID- 10062511
TI  - Friction Fluctuations and Friction Memory in Stick-Slip Motion.

PMID- 10062512
TI  - Extension of Onsager's Reciprocity to Large Fields and the Chaotic Hypothesis.

PMID- 10062514
TI  - Small-Scale-Field Dynamo.

PMID- 10062513
TI  - Steady Viscous Flow with Fractal Power Spectrum.

PMID- 10062515
TI  - Dipole Density Solitons and Solitary Dipole Vortices in an Inhomogeneous Space
      Plasma.

PMID- 10062516
TI  - Measurements of Electron Temperature by Spectroscopy in Hohlraum Targets.

PMID- 10062517
TI  - New Mechanism for Three-Dimensional Current Dissipation/Reconnection in
      Astrophysical Plasmas.

PMID- 10062518
TI  - Event-Based Relaxation of Continuous Disordered Systems.

PMID- 10062519
TI  - H

PMID- 10062521
TI  - Modeling of Covalent Bonding in Solids by Inversion of Cohesive Energy Curves.

PMID- 10062520
TI  - Rigid H2O Molecule Model of Anomalous Thermal Expansion of Ices.

PMID- 10062522
TI  - Plastic Flow Induced by Single Ion Impacts on Gold.

PMID- 10062524
TI  - Anomalous Temperature Dependence of the X-Ray Diffuse Scattering Intensity of
      Cu>3Au.

PMID- 10062523
TI  - Scaling Behavior of Block Copolymers in Spontaneous Growth of Lamellar Domains.

PMID- 10062525
TI  - Liquid-Liquid Immiscibility in Pure Fluids: Polyamorphism in Simulations of a
      Network-Forming Fluid.

PMID- 10062527
TI  - Early Stage of Spinodal Decomposition in 2D.

PMID- 10062526
TI  - Shear-Induced Sponge-to-Lamellar Transition in a Hyperswollen Lyotropic System.

PMID- 10062528
TI  - Disappearance of Roton Propagation in Superfluid 4He at T lambda.

PMID- 10062529
TI  - Atomic Structure of the Sb-Stabilized GaAs(100)-(2 x 4) Surface.

PMID- 10062531
TI  - Dispersive-Transport-Controlled Luminescence in Hydrogenated Amorphous Silicon.

PMID- 10062530
TI  - Anyons and Chiral Solitons on a Line.

PMID- 10062532
TI  - Diffusion of Electrons in Quasi-1D Polymer Structures with Random Interchain
      Couplings.

PMID- 10062533
TI  - Quantum Numbers of Textured Hall Effect Quasiparticles.

PMID- 10062534
TI  - Bragg Resonances for Tunneling Between Edges of a 2D Quantum Hall System.

PMID- 10062535
TI  - Critical Conductance and Its Fluctuations at Integer Hall Plateau Transitions.

PMID- 10062536
TI  - Linear-Response Calculation of the Electron-Phonon Coupling in Doped CaCuO2.

PMID- 10062537
TI  - Resonance Raman Study of the Superconducting Gap and Low Energy Excitations in
      Tl2Ba2CuO6+ delta Superconductors.

PMID- 10062538
TI  - Large Dynamical Fluctuations in the Microwave Conductivity of YBa2Cu3O7- delta
      above Tc.

PMID- 10062539
TI  - Velocity Selection for Propagating Fronts in Superconductors.

PMID- 10062540
TI  - Dimensional Crossover in Quantum Antiferromagnets.

PMID- 10062541
TI  - In-Plane Magnetic Anisotropy of Ultrathin bcc (110) Transition-Metal Films.

PMID- 10062542
TI  - Hydrodynamic Solutions for a Sonoluminescing Gas Bubble.

PMID- 10062543
TI  - Voltage Fluctuations and Collective Effects in Ion-Channel Protein Ensembles.

PMID- 10062544
TI  - Front Propagation and Local Ordering in One-Dimensional Irreversible
      Autocatalytic Reactions.

PMID- 10062545
TI  - Oscillatory Hydrodynamic Flow due to Concentration Dependence of Surface Tension.

PMID- 10062546
TI  - Subdiffusion and Anomalous Local Viscoelasticity in Actin Networks.

PMID- 10062547
TI  - Charge Localization and Dynamics in Rhodopsin.

PMID- 10062548
TI  - Control of Radical Pair Lifetime by a Switched Magnetic Field.

PMID- 10062549
TI  - Vortex Dynamics in Two-Dimensional Amorphous Mo77Ge23 Films

PMID- 10062550
TI  - Colliding Black Holes: How Far Can the Close Approximation Go?

PMID- 10062551
TI  - Gravitomagnetic Induction during the Coalescence of Compact Binaries.

PMID- 10062552
TI  - Four-Dimensional Greybody Factors and the Effective String.

PMID- 10062553
TI  - Analytic Scaling Solutions for Cosmic Domain Walls.

PMID- 10062554
TI  - Supersymmetric Grand Unified Theory Contributions and Model Independent
      Extractions of CP Phases.

PMID- 10062556
TI  - Investigating the Evolution of Multifragmenting Systems with Fragment Emission
      Order.

PMID- 10062555
TI  - Search for Nonresonant B+-->h+h-h+ Decays.

PMID- 10062558
TI  - Hydrogen Molecule as a Classical Restricted Four-Body Problem.

PMID- 10062557
TI  - Radiative Muon Capture on Hydrogen and the Induced Pseudoscalar Coupling.

PMID- 10062559
TI  - Imaging of Saddle Point Electron Emission in Slow p-He Collisions.

PMID- 10062560
TI  - Energy Dissipation in Small Clusters: Direct Photoemission, Dissociation, and
      Thermionic Emission.

PMID- 10062561
TI  - Photoelectron Spectra and Geometric Structures of Small Niobium Cluster Anions.

PMID- 10062563
TI  - Field Theory of the Quantum Kicked Rotor.

PMID- 10062562
TI  - Spin Polarized Alkali Clusters: Observation of Quartet States of the Sodium
      Trimer.

PMID- 10062564
TI  - Propagation of Waves in the Spectrum of a Multimode Laser.

PMID- 10062565
TI  - Vortex Evolution and Bound Pair Formation in Anisotropic Nonlinear Optical Media.

PMID- 10062566
TI  - Isotropic Turbulence: Important Differences between True Dissipation Rate and Its
      One-Dimensional Surrogate.

PMID- 10062567
TI  - Do Hydrodynamic Dispersion Coefficients Exist?

PMID- 10062568
TI  - Propagation of Subpicosecond Laser Pulses through a Fully Ionized Plasma.

PMID- 10062569
TI  - Renormalization of Nonequilibrium Systems with Critical Stationary States.

PMID- 10062570
TI  - Liquid-Crystal Phase Transitions Induced by Microtextured Substrates.

PMID- 10062571
TI  - Effect of Magnetic Scattering on the 3He Superfluid State in Aerogel.

PMID- 10062572
TI  - Edward-Wilkinson Behavior of Crystal Surfaces Grown By Sedimentation of SiO2
      Nanospheres.

PMID- 10062573
TI  - Femtosecond Laser-Induced Desorption of CO from Cu(100): Comparison of Theory and
      Experiment.

PMID- 10062574
TI  - Epitaxial Growth of Metastable Co-Cu Alloys by a Surface Pump Mechanism.

PMID- 10062575
TI  - Step-Adatom Attraction as a New Mechanism for Instability in Epitaxial Growth.

PMID- 10062576
TI  - The Anharmonic Electron-Phonon Problem.

PMID- 10062577
TI  - Quantum Transition between an Antiferromagnetic Mott Insulator and dx2 -y2
      Superconductor in Two Dimensions.

PMID- 10062578
TI  - Self-Pulse-Shaping Coherent Control of Excitons in a Semiconductor Microcavity.

PMID- 10062579
TI  - Electronic Structure of Band-Tail Electrons in a Si:H.

PMID- 10062580
TI  - Spin Excitations of a Two-Dimensional Electron Gas in the Limit of Vanishing
      Lande g Factor.

PMID- 10062581
TI  - Nonlinear Magneto-Optical Response from Quantum Well States in Noble Metals:
      Double Period and Interface Localization.

PMID- 10062582
TI  - Nonuniversal Conductance Quantization in Quantum Wires.

PMID- 10062583
TI  - New Concept for the Reduction of Impurity Scattering in Remotely Doped GaAs
      Quantum Wells.

PMID- 10062584
TI  - Optical Study on Phonon Anomalies and Spin Gap in YBa2(Cu1-xZnx)3O6.6.

PMID- 10062585
TI  - Evidence for Large Static and Dynamic Distortions in High Tc Superconducting
      YBa2Cu3O 7- delta Crystals over a Wide Temperature Range.

PMID- 10062586
TI  - Anomalous Phonon Scattering Below Tc in YNi2 11B2C.

PMID- 10062587
TI  - c Axis Superfluid Response of Copper Oxide Superconductors.

PMID- 10062588
TI  - Strong Pinning and Plastic Deformations of the Vortex Lattice.

PMID- 10062589
TI  - Thermodynamic Density Matrix Renormalization Group Study of the Magnetic
      Susceptibility of Half-Integer Quantum Spin Chains.

PMID- 10062590
TI  - Thresholds of Envelope Soliton Formation in a Weakly Dissipative Medium.

PMID- 10062591
TI  - Spin Glass Dynamics under a Change in Magnetic Field.

PMID- 10062592
TI  - Metal-Insulator Transition and Giant Negative Magnetoresistance in Amorphous
      Magnetic Rare Earth Silicon Alloys.

PMID- 10062593
TI  - Chemical Bonding and Size-Scaling of Nonlinear Polarizabilities of Conjugated
      Polymers.

PMID- 10062594
TI  - Continuous Shear Thickening and Colloid Surfaces.

PMID- 10062595
TI  - Measurement of Phase and Magnitude of the Reflection Coefficient of a Quantum
      Dot.

PMID- 10062597
TI  - On-line versus Off-line Learning from Random Examples: General Results.

PMID- 10062596
TI  - Two-Dimensional Child-Langmuir Law.

PMID- 10062598
TI  - Size Enhancement of Transition Dipoles to One- and Two-Exciton Bands in a
      Photosynthetic Antenna.

PMID- 10062600
TI  - Quantum Logical Operations on Encoded Qubits.

PMID- 10062599
TI  - Noise-Mediated Spike Timing Precision from Aperiodic Stimuli in an Array of
      Hodgekin-Huxley-Type Neurons.

PMID- 10062602
TI  - Comment on "Local Magnetism and Crystal Fields of Pr in PrBa2Cu3O7 Studied by
      141Pr NMR"

PMID- 10062601
TI  - Comment on "Transverse Force on a Quantized Vortex in a Superfluid"

PMID- 10062603
TI  - Nehrke and Pieper Reply.

PMID- 10062605
TI  - Eberlein Replies.

PMID- 10062604
TI  - Comment on "Sonoluminescence as Quantum Vacuum Radiation"

PMID- 10062607
TI  - Field Theories for Learning Probability Distributions.

PMID- 10062609
TI  - Gravitational Instantons and Minimal Surfaces.

PMID- 10062608
TI  - Spatiotemporal Stochastic Resonance in a System of Coupled Diode Resonators.

PMID- 10062610
TI  - Observational Constraints on Open Inflation Models.

PMID- 10062612
TI  - Nonperturbative Relations in N=2 Supersymmetric Yang-Mills Theory and the Witten
      Dijkgraaf-Verlinde-Verlinde Equation.

PMID- 10062611
TI  - The Russian-American gallium experiment (SAGE) Cr Neutrino source measurement.

PMID- 10062613
TI  - Model-Independent Extraction of the N*(1535) Electrostrong Form Factor from Eta
      Electroproduction.

PMID- 10062614
TI  - Alpha-Particle Angular Distributions of At and Rn Isotopes and Their Relation to
      Nuclear Structure.

PMID- 10062615
TI  - Calculation of the beta -Decay Spectrum of the T2 Molecule beyond the Sudden
      Impulse Approximation.

PMID- 10062616
TI  - Quantum Reservoir Engineering with Laser Cooled Trapped Ions.

PMID- 10062617
TI  - Level-Crossing Resonances in Nuclear Spin Conversion of Molecules.

PMID- 10062618
TI  - Quantum Optical Effects and Nonlinear Dynamics in Interacting Electron Systems.

PMID- 10062619
TI  - Sustaining Chaos by Using Basin Boundary Saddles.

PMID- 10062620
TI  - Diffusion and Localization in Chaotic Billiards.

PMID- 10062622
TI  - Double Butterfly Spectrum for Two Interacting Particles in the Harper Model.

PMID- 10062621
TI  - Suppression of Chaotic Diffusion by Quenched Disorder.

PMID- 10062623
TI  - Spatial Coherence Measurement of Soft X-Ray Radiation Produced by High Order
      Harmonic Generation.

PMID- 10062624
TI  - Propagation of Elastic Waves in Deep Vertically Shaken Particle Beds.

PMID- 10062626
TI  - Hysteretic Creep of Elastic Manifolds.

PMID- 10062625
TI  - Demonstration of Microwave Generation from a Static Field by a Relativistic
      Ionization Front in a Capacitor Array.

PMID- 10062627
TI  - Direct Observation of (B12)(B12)12 Supericosahedra as the Basic Structural
      Element in YB66.

PMID- 10062628
TI  - Breather Mobility in Discrete phi4 Nonlinear Lattices.

PMID- 10062629
TI  - Theory of Branching and Annihilating Random Walks.

PMID- 10062630
TI  - Diffusion of Boron in Copper by Direct-Exchange Mechanism.

PMID- 10062631
TI  - Undulations and Dynamic Structure Factor of Membranes.

PMID- 10062632
TI  - Motional Narrowing in Semiconductor Microcavities.

PMID- 10062633
TI  - Coherent ab and c Transport Theory of High-Tc Cuprates.

PMID- 10062634
TI  - Spin-Peierls States of Quantum Antiferromagnets on the CaV4O9 Lattice.

PMID- 10062635
TI  - Exact Results for Quantum Phase Transitions in Random XY Spin Chains.

PMID- 10062636
TI  - Transverse X-Ray Coherence in Nuclear Scattering of Synchrotron Radiation.

PMID- 10062637
TI  - Interstitial-Carbon Hydrogen Interaction in Silicon.

PMID- 10062638
TI  - Sonoluminescence in High Magnetic Fields.

PMID- 10062639
TI  - Theory of Exciton Migration and Field-Induced Dissociation in Conjugated
      Polymers.

PMID- 10062640
TI  - Charge Redistribution in Pd-Ag Alloys from a Local Perspective.

PMID- 10062642
TI  - Phase Diagram of Colloidal Solutions.

PMID- 10062641
TI  - Ab Initio Ammonia and CO Lateral Interactions on Pt(111).

PMID- 10062643
TI  - Experimental Operation of a Cyclotron Autoresonance Maser Oscillator at the
      Second Harmonic.

PMID- 10062644
TI  - Magnetic Levitation and Noncoalescence of Liquid Helium.

PMID- 10062645
TI  - Emergence of Chaos in Asymmetric Networks.

PMID- 10062646
TI  - Comment on "Extreme State of a Charged Black Hole in a Grand Canonical Ensemble"

PMID- 10062647
TI  - Comment on "Two Phase Transitions in the Fully Frustrated XY Model"

PMID- 10062648
TI  - Olsson Replies.

PMID- 10062649
TI  - 1D Generalized Statistics Gas: A Gauge Theory Approach

PMID- 10062650
TI  - Electromagnetic Beam Breakup: Multiple Filaments, Single Beam Equilibria, and
      Radiation

PMID- 10062651
TI  - Spiral-Defect Chaos in Rayleigh-Benard Convection with Small Prandtl Numbers

PMID- 10062652
TI  - Algebraic Relaxation Laws for Classical Particles in 1D Anharmonic Potentials.

PMID- 10062653
TI  - Oscillatory Behavior of the Rate of Escape through an Unstable Limit Cycle.

PMID- 10062654
TI  - Large Quantum Gravity Effects: Unforeseen Limitations of the Classical Theory.

PMID- 10062656
TI  - Pulsar Velocities and Neutrino Oscillations.

PMID- 10062655
TI  - Universal Formula for Noncommutative Geometry Actions: Unification of Gravity and
      the Standard Model.

PMID- 10062657
TI  - Macroscopic Universality: Why QCD in Matter is Subtle.

PMID- 10062658
TI  - 1P1 Charmonium Production at the Fermilab Tevatron.

PMID- 10062660
TI  - Observing the Progressive Decoherence of the "Meter" in a Quantum Measurement.

PMID- 10062659
TI  - K+ Emission in Symmetric Heavy Ion Reactions at Subthreshold Energies.

PMID- 10062661
TI  - Production of Water Molecules from Dissociative Recombination of H3O + with
      Electrons.

PMID- 10062662
TI  - Thermal Isomerization in Isolated Cesium-Halide Clusters.

PMID- 10062663
TI  - Early Crisis Induced in Maps with Parametric Noise.

PMID- 10062664
TI  - Lower and Upper Bounds on Internal-Wave Frequencies in Stratified Rotating
      Fluids.

PMID- 10062665
TI  - Study of Laser-Hole Boring into Overdense Plasmas.

PMID- 10062666
TI  - Network Domain Structure in Viscoelastic Phase Separation.

PMID- 10062667
TI  - Structural Evidence for a Fast-Ion Transition in the High-Pressure Rocksalt Phase
      of Silver Iodide.

PMID- 10062668
TI  - Symmetry Breaking and Spectral Statistics of Acoustic Resonances in Quartz
      Blocks.

PMID- 10062670
TI  - Novel Dopant Activation of Heavily Doped p+-Si by High Current Densities.

PMID- 10062669
TI  - Surface Structure and Relaxation at the Pt(110)/Electrolyte Interface.

PMID- 10062671
TI  - An Exactly Solvable Kondo Problem for Interacting One-Dimensional Fermions.

PMID- 10062673
TI  - Luminescence Hole Burning and Quantum Size Effect of Charged Excitons in CuCl
      Quantum Dots.

PMID- 10062674
TI  - Quantum Size Effects in Epitaxial ErAs on GaAs(001).

PMID- 10062672
TI  - Electric Field Scaling at a B=0 Metal-Insulator Transition in Two Dimensions.

PMID- 10062675
TI  - Reentrance of the Metallic Conductance in a Mesoscopic Proximity Superconductor.

PMID- 10062676
TI  - Transport in MultiTerminal Normal-Superconductor Devices: Reciprocity Relations,
      Negative and Nonlocal Resistances, and Reentrance of the Proximity Effect.

PMID- 10062677
TI  - Van der Waals Attraction of Vortices in Anisotropic and Layered Superconductors.

PMID- 10062678
TI  - Effect of Level Statistics on Superconductivity in Ultrasmall Metallic Grains.

PMID- 10062679
TI  - Origin of Entropy Convergence in Hydrophobic Hydration and Protein Folding.

PMID- 10062680
TI  - Two-state, r=1 Cellular Automaton that Classifies Density.

PMID- 10062681
TI  - Comment on "Measurements of Higher Order Photon Bunching of Light Beams"

PMID- 10062682
TI  - Singh and Cantrell Reply.

PMID- 10062684
TI  - Complex Periodic Orbits and Tunneling in Chaotic Potentials.

PMID- 10062685
TI  - Atom Waves in Crystals of Light.

PMID- 10062687
TI  - Temporally Disordered Bond Percolation on the Directed Square Lattice.

PMID- 10062686
TI  - Bose-Einstein Condensation in a Dilute Gas: Measurement of Energy and Ground
      State Occupation.

PMID- 10062688
TI  - Moduli, Scalar Charges, and the First Law of Black Hole Thermodynamics.

PMID- 10062689
TI  - Resonant CP-Violating Scalar-Pseudoscalar Transitions at micro+ micro- Colliders.

PMID- 10062691
TI  - Measurement of the gamma +D*+/- Cross Section in p-barp Collisions at sqrt s=1.8
      TeV.

PMID- 10062690
TI  - First Measurement of the B--> pi l nu and B--> rho ( omega )l nu Branching
      Fractions.

PMID- 10062692
TI  - Isolated Photon Cross Section in the Central and Forward Rapidity Regions in pp
      bar Collisions at sqrt s=1.8 TeV.

PMID- 10062693
TI  - Measurements of Spectroscopic Quadrupole Moments of Neutron Deficient Ir Isotopes
      and Shape Coexistence in 186Ir.

PMID- 10062694
TI  - Study of the Breakup Reaction 8B-->7Be+p: Absorption Effects and E2 Strength.

PMID- 10062696
TI  - Anomalous Peaklike Structure in the Fission Fragment Anisotropies at Sub-barrier
      Energies in 11B, 12C, 16O, 19F+232Th Reactions.

PMID- 10062695
TI  - Energy-Averaged Parity Nonconserving Effect in Neutron Scattering from Heavy
      Nuclei.

PMID- 10062697
TI  - Elastic Rescattering in the Strong Field Tunneling Limit.

PMID- 10062698
TI  - Quenching of Symmetry Breaking in Resonant Inelastic X-Ray Scattering by Detuned
      Excitation.

PMID- 10062699
TI  - Blowout Bifurcation Route to Strange Nonchaotic Attractors.

PMID- 10062700
TI  - Susceptibility of Chaotic Systems to Perturbations.

PMID- 10062701
TI  - Noise-Induced Riddling in Chaotic Systems.

PMID- 10062702
TI  - Origin of Spiral Wave Formation in Excitable Optical Systems.

PMID- 10062703
TI  - Experimental Evidence for Chaotic Scattering in a Fluid Wake.

PMID- 10062704
TI  - Formation of Electric Field Spikes in Electron-Beam-Plasma Interaction.

PMID- 10062705
TI  - Improved Symmetry Greatly Increases X-Ray Power from Wire-Array Z-Pinches.

PMID- 10062706
TI  - Thermal Diffusion Processes in Metal-Tip-Surface Interactions: Contact Formation
      and Adatom Mobility.

PMID- 10062707
TI  - Real Space Investigation of the Roughening and Deconstruction Transitions of
      Au(110).

PMID- 10062708
TI  - Localization-Delocalization Transition for Drift Diffusion in a Random
      Environment.

PMID- 10062709
TI  - Eulerian Walkers as a Model of Self-Organized Criticality.

PMID- 10062710
TI  - Ionic Diffusion in a Ternary Superionic Conductor: An Ab Initio Molecular
      Dynamics Study.

PMID- 10062712
TI  - Reconstruction and Thermal Stability of the Cubic SiC (001) Surfaces.

PMID- 10062711
TI  - Vortex Mutual Friction, Orbital Inertia, and History-Dependent Textures in
      Rotating Superfluid 3He -A.

PMID- 10062713
TI  - Anisotropic Surface Growth Model in Disordered Media.

PMID- 10062715
TI  - Exact Shape of the Lowest Landau Level in a Double-Layer System and a
      Superlattice with Uncorrelated Disorder.

PMID- 10062714
TI  - Phase String Effect in a Doped Antiferromagnet.

PMID- 10062716
TI  - Mesoscopic Effects in the Fractional Quantum Hall Regime: Chiral Luttinger Liquid
      versus Fermi Liquid.

PMID- 10062718
TI  - Vortex Lattice Structure in Bi2Sr2CaCu2O8+ delta at High Temperatures.

PMID- 10062717
TI  - Dynamical Phase Transition in a Driven Disordered Vortex Lattice.

PMID- 10062719
TI  - Monte Carlo Simulations of a Disordered Lattice London Model.

PMID- 10062720
TI  - Kondo Screening and Magnetic Ordering in Frustrated UNi4B.

PMID- 10062721
TI  - Simulations of Discrete Quantum Systems in Continuous Euclidean Time.

PMID- 10062722
TI  - Onsager Reaction Field in Itinerant Magnetism.

PMID- 10062723
TI  - Temperature-Dependent Spin Polarization of Magnetic Surface State at Gd(0001).

PMID- 10062724
TI  - First Order Transition in the Frustrated Antiferromagnetic Heisenberg S=1 Quantum
      Spin Chain.

PMID- 10062725
TI  - Comment on the "Lack of Destructive Interference of Landau Edge States in the
      Quantum Hall Regime"

PMID- 10062726
TI  - Muller Replies.

PMID- 10062728
TI  - New Monitoring Parameter for the Traveling Salesman Problem.

PMID- 10062729
TI  - Two-Ion Interference: Bragg Scattering and Superradiance.

PMID- 10062730
TI  - Quantum Action-Angle Variables for the Harmonic Oscillator.

PMID- 10062731
TI  - Coherent Frequency Shift of Atomic Matter Waves.

PMID- 10062732
TI  - Dirty Black Holes and Hairy Black Holes.

PMID- 10062733
TI  - Supersymmetric Photonic Signals at the CERN e+e- Collider LEP in Light Gravitino
      Models.

PMID- 10062734
TI  - Determining the tt-bar and ZZ Couplings of a Neutral Higgs Boson of Arbitrary CP
      Nature at the Next Linear Collider.

PMID- 10062735
TI  - Measurement of the Branching Fraction B(B+u-->J/ psi pi +) and Search for B+c-
      >J/ psi pi +

PMID- 10062736
TI  - Additivity of Quadrupole Moments in Superdeformed Bands: Single-Particle Motion
      at Extreme Conditions.

PMID- 10062737
TI  - Double Beta Decay of 48Ca.

PMID- 10062738
TI  - Observation of Bound-State beta - Decay of Fully Ionized 187Re: 187Re-187Os
      Cosmochronometry.

PMID- 10062739
TI  - Observation of a Shape Resonance in Cold-Atom Scattering by Pulsed
      Photoassociation.

PMID- 10062740
TI  - High Intensity Pulse Propagation in the Extreme Sharp-Line Limit.

PMID- 10062741
TI  - Partial Dynamical Symmetry and Mixed Dynamics.

PMID- 10062742
TI  - Demonstration of Soft X-Ray Lasing to Ground State in Li III.

PMID- 10062743
TI  - Stability of Three-Wave Parametric Solitons in Diffractive Quadratic Media.

PMID- 10062744
TI  - Abrupt Changes in Confinement in the JET Tokamak.

PMID- 10062745
TI  - Persistence Length for a PSSNa Polyion in Semidilute Solution as a Function of
      the Ionic Strength.

PMID- 10062746
TI  - Orientational Wetting in Hybrid Liquid Crystalline Block Copolymers.

PMID- 10062747
TI  - Slow Relaxation Phenomena Induced by Breathers in Nonlinear Lattices.

PMID- 10062748
TI  - Corrals and Critical Behavior of the Distribution of Fluctuational Paths.

PMID- 10062749
TI  - Mn Self-Diffusion in Single Grain Icosahedral Al70Pd21.5Mn8.5 Quasicrystals.

PMID- 10062750
TI  - Role of Bilayer Tilt Difference in Equilibrium Membrane Shapes.

PMID- 10062751
TI  - Substrate-Adsorbate Coupling in CO-Adsorbed Copper.

PMID- 10062752
TI  - Probing the A-B Phase Interface in Superfluid 3He by Andreev Reflection of a
      Quasiparticle Beam.

PMID- 10062753
TI  - Overpotential-Controlled Nucleation of Ni Island Arrays on Reconstructed Au(111)
      Electrode Surfaces.

PMID- 10062754
TI  - Mechanism of the Giant Magnetoresistance in UNiGa from First-Principles
      Calculations.

PMID- 10062755
TI  - Excitonic Nonlinearities of Semiconductor Microcavities in the Nonperturbative
      Regime.

PMID- 10062756
TI  - Third Angular Effect of Magnetoresistance in Quasi-One-Dimensional Conductors.

PMID- 10062758
TI  - Imaging and Spectroscopy of Single InAs Self-Assembled Quantum Dots using
      Ballistic Electron Emission Microscopy.

PMID- 10062757
TI  - Universal Crossover between Efros-Shklovskii and Mott Variable-Range-Hopping
      Regimes.

PMID- 10062759
TI  - "Spectator" Modes and Antidot Molecules.

PMID- 10062760
TI  - Random Matrix Model for Superconductors in a Magnetic Field.

PMID- 10062762
TI  - Square Lattice Self-Avoiding Walks and Corrections to Scaling.

PMID- 10062761
TI  - Unusual Vortex Dynamics in Nb-a-Si Multilayers with Strong Interlayer Coupling.

PMID- 10062764
TI  - Higher Dimensional Realizations of Activated Dynamic Scaling at Random Quantum
      Transitions.

PMID- 10062763
TI  - Scaling Properties of Suboptimal Interfaces.

PMID- 10062765
TI  - EPR Evidence of Jahn-Teller Polaron Formation in La1-xCaxMnO3+y.

PMID- 10062766
TI  - Ab Initio Theory of NMR Chemical Shifts in Solids and Liquids.

PMID- 10062767
TI  - Strong Critical Enhancement of the Shear Viscosity of Colloidal Systems.

PMID- 10062768
TI  - Comment on "Nuclear Magnetic Ordering of 3He Clusters in Solid 4He"

PMID- 10062769
TI  - Schrenk, Konig, and Pobell Reply.

PMID- 10062770
TI  - Comment on "Nuclear Magnetic Ordering of 3He Clusters in Solid 4He"

PMID- 10062771
TI  - Schrenk, Konig, and Pobell Reply.

PMID- 10062773
TI  - Bose-Einstein Condensates in Time Dependent Traps.

PMID- 10062774
TI  - Low Energy Excitations of a Bose-Einstein Condensate: A Time-Dependent
      Variational Analysis.

PMID- 10062775
TI  - Path Integral Solution of the Kramers Problem.

PMID- 10062776
TI  - Kramers Rate for Thermal Plus Dichotomous Noise Applied to Ratchets.

PMID- 10062777
TI  - Observation of Light Confinement Effects with a Near-Field Optical Microscope.

PMID- 10062779
TI  - Precise Determination of the Pion-Nuclear Coupling Parameter from Weak Processes
      in 3He.

PMID- 10062780
TI  - P,T-Odd Spin-Rotational Hamiltonian for YbF Molecule.

PMID- 10062778
TI  - Measurement of Dijet Angular Distributions by the Collider Detector at Fermilab.

PMID- 10062781
TI  - Element 118: The First Rare Gas with an Electron Affinity.

PMID- 10062782
TI  - Observation of Lifetime-Limited X-Ray Linewidths in Cold Highly Charged Ions.

PMID- 10062783
TI  - Electromagnetically Induced Transparency in an Ideal Plasma.

PMID- 10062785
TI  - Light Induced Single Molecule Frequency Shift.

PMID- 10062784
TI  - Transitions to Bubbling of Chaotic Systems.

PMID- 10062786
TI  - Developed Turbulence: From Full Simulations to Full Mode Reductions.

PMID- 10062787
TI  - Self-Excitation of Fluctuations of Inertial Particle Concentration in Turbulent
      Fluid Flow.

PMID- 10062789
TI  - Temporal Characterization of a Self-Modulated Laser Wakefield.

PMID- 10062788
TI  - Temporal Evolution of Self-Modulated Laser Wakefields Measured by Coherent
      Thomson Scattering.

PMID- 10062790
TI  - Dynamics of Random Hydrophobic-Hydrophilic Copolymers with Implications for
      Protein Folding.

PMID- 10062791
TI  - Straightening of Thermal Fluctuations in Semiflexible Polymers by Applied
      Tension.

PMID- 10062792
TI  - Scaling Relations for the Lengths and Widths of Fractures.

PMID- 10062793
TI  - Phonon Poiseuille Flow in Quasi-One-Dimensional Single Crystals.

PMID- 10062794
TI  - Rotons and Roton Wave Packets in Superfluid 4He.

PMID- 10062795
TI  - Band-Gap Engineering by III-V Infill in Sodalite.

PMID- 10062796
TI  - Isolated Hydrogen Molecules in GaAs.

PMID- 10062797
TI  - Carrier-Controlled Doping Efficiency in La2CuO4+ delta.

PMID- 10062798
TI  - Insulator-to-Metal Crossover in the Normal State of La2-xSrxCuO 4 Near Optimum
      Doping.

PMID- 10062799
TI  - Muon Spin Relaxation Studies of Zn-Substitution Effects in High-Tc Cuprate
      Superconductors.

PMID- 10062800
TI  - Magnetic Dynamics in Underdoped YBa2Cu3O7-x: Direct Observation of a
      Superconducting Gap.

PMID- 10062801
TI  - Ultrafast Electron Redistribution through Coulomb Scattering in Undoped GaAs:
      Experiment and Theory.

PMID- 10062802
TI  - Chain Length Scaling of Protein Folding Time.

PMID- 10062803
TI  - Photon Correlation Spectroscopy of Colloidal Palladium Using a Coherent X-Ray
      Beam.

PMID- 10062806
TI  - All-Optical Model for the Generation and the Detection of Macroscopic Quantum
      Coherence.

PMID- 10062804
TI  - Comment on "Stability of a Solitary Pulse against Wave Packet Disturbances in an
      Active Medium"

PMID- 10062807
TI  - Bose-Einstein Condensation in a Tightly Confining dc Magnetic Trap.

PMID- 10062808
TI  - Collective Excitations of a Bose-Einstein Condensate in a Dilute Gas.

PMID- 10062809
TI  - Critical Behavior in Gravitational Collapse of a Yang-Mills Field.

PMID- 10062810
TI  - Statistical Entropy of Four-Dimensional Extremal Black Holes.

PMID- 10062811
TI  - Statistical Entropy of Nonextremal Four-Dimensional Black Holes and U-Duality.

PMID- 10062812
TI  - Proposed micro-->e gamma Search with Polarized Muons.

PMID- 10062813
TI  - Inclusive Jet Cross Section in p-barp Collisions at sqrt s=1.8 TeV.

PMID- 10062814
TI  - Large Transverse Momentum Jet Production and the Gluon Distribution inside the
      Proton.

PMID- 10062816
TI  - Beta-Decay Half-Lives and Neutron-Emission Probabilities of Very Neutron-Rich Y
      to Tc Isotopes.

PMID- 10062815
TI  - Properties of Jets in Z Boson Events from 1.8 TeV p-barp Collisions.

PMID- 10062817
TI  - Direct Measurement of Dissipation in the 35Cl+12C Reaction at 43 MeV/nucleon.

PMID- 10062818
TI  - Critical Phenomena for Electronic Structure at the Large-Dimension Limit.

PMID- 10062819
TI  - Evidence for a Resonance State of H2-

PMID- 10062821
TI  - Interaction between Two-Level Atoms and a Squeezed Vacuum in a Cavity: Effect on
      the Mean Photon Number.

PMID- 10062820
TI  - Double Scattering Effects in the Ionization Spectrum Produced by Single Energetic
      Atomic Collisions.

PMID- 10062822
TI  - Geometrical Resonance as a Chaos Eliminating Mechanism.

PMID- 10062823
TI  - Cluster Expansion for Collective Behavior in Discrete-Space Dynamical Systems.

PMID- 10062824
TI  - Self-Trapping of Partially Spatially Incoherent Light.

PMID- 10062825
TI  - Local Negative Shear and the Formation of Transport Barriers.

PMID- 10062826
TI  - Supersonic Ionization Wave Driven by Radiation Transport in a Short-Pulse Laser
      Produced Plasma.

PMID- 10062827
TI  - An Explanation for Positive Differential dc Voltage-Current Characteristics in
      Weakly Ionized, Low-Pressure Positive Column Gas Discharge Plasmas.

PMID- 10062829
TI  - Inner Patterns and Front Propagation of a Dynamic Random Impurity Model.

PMID- 10062828
TI  - Thermodynamic Effects on Internal Relaxation in Diblock Copolymers.

PMID- 10062830
TI  - Phase Transitions in Driven Bilayer Systems: A Monte Carlo Study.

PMID- 10062831
TI  - First-Principles Calculations of Absolute Concentrations and Self-Diffusion
      Constants of Vacancies in Lithium.

PMID- 10062832
TI  - Evidence of a Phenomenon of Epitaxy at the Interface between a Lamellar L alpha
      Phase and a L3 Sponge.

PMID- 10062833
TI  - Vicinal Surfaces and the Calogero-Sutherland Model.

PMID- 10062834
TI  - Entropic Step Doubling on W(430).

PMID- 10062835
TI  - Coadsorbate Induced Reconstruction of a Stepped Pt(111) Surface by Sulfur and CO:
      A Novel Surface Restructuring Mechanism Observed by Scanning Tunneling
      Microscopy.

PMID- 10062837
TI  - Charge-Dipole Model for the Universal Field Dependence of Mobilities in
      Molecularly Doped Polymers.

PMID- 10062836
TI  - Voltage-Biased Quantum Wire with Impurities.

PMID- 10062838
TI  - Ab Initio Study of N Impurity in Amorphous Germanium.

PMID- 10062839
TI  - Dynamic Evolution of Spatiotemporally Localized Electronic Wave Packets in
      Semiconductor Quantum Wells.

PMID- 10062840
TI  - Random Walks through the Ensemble: Linking Spectral Statistics with Wave-Function
      Correlations in Disordered Metals.

PMID- 10062841
TI  - Evidence of Nonlocal Breakdown of the Integer Quantum Hall Effect.

PMID- 10062842
TI  - Effects of Geometric Phases in Josephson Junction Arrays.

PMID- 10062843
TI  - Electrostatics of Vortices in Type-II Superconductors.

PMID- 10062844
TI  - Localization Transitions in Non-Hermitian Quantum Mechanics.

PMID- 10062845
TI  - Resonant X-Ray Fluorescence Spectroscopy of Correlated Systems: A Probe of Charge
      Transfer Excitations.

PMID- 10062846
TI  - Origin of Stratification in Creaming Emulsions.

PMID- 10062847
TI  - Kink Drift in Oscillating Fields.

PMID- 10062848
TI  - Sukstanskii and Primak Reply.

PMID- 10062849
TI  - Comment on "Viscosity and Structural Relaxation in Suspensions of Hard-Sphere
      Colloids"

PMID- 10062850
TI  - Segre et al. Reply.

PMID- 10062852
TI  - A Low-Density Closed Universe.

PMID- 10062853
TI  - A Dark Matter Solution from the Supersymmetric Axion Model.

PMID- 10062855
TI  - Quark Resonances and High Et Jets.

PMID- 10062857
TI  - Temperature Dependence of the Width of the Giant Dipole Resonance in 120Sn and
      208Pb.

PMID- 10062854
TI  - Azimuthal Decorrelation of Jets Widely Separated in Rapidity.

PMID- 10062856
TI  - A Dependence of the ( pi +, pi + pi +/-) Reaction near the 2m pi Threshold.

PMID- 10062858
TI  - Angular Distribution for the 7Be(d,n)8B Reaction at Ec.m.=5.8 MeV and the S17(0)
      Factor for the 7Be(p, gamma )8B Reaction.

PMID- 10062859
TI  - Motion Induced Radiation from a Vibrating Cavity.

PMID- 10062860
TI  - Highly Accurate Solution for a Hydrogen Atom in a Uniform Magnetic Field.

PMID- 10062861
TI  - Efficient, Indirect Transverse Laser Cooling of a Fast Stored Ion Beam.

PMID- 10062862
TI  - Experimental Observation of a Large Excess Quantum Noise Factor in the Linewidth
      of a Laser Oscillator Having Nonorthogonal Modes.

PMID- 10062863
TI  - Photon Correlation Spectroscopy.

PMID- 10062864
TI  - Improved Surrogate Data for Nonlinearity Tests.

PMID- 10062865
TI  - Anisotropic Light Diffusion in Oriented Nematic Liquid Crystals.

PMID- 10062866
TI  - Motion of an Asymmetric Ferrofluid Drop under a Homogeneous Time-Dependent
      Magnetic Field.

PMID- 10062867
TI  - Cooperative Particle Motions and Dynamical Behaviors of Free Dislocations in
      Strongly Coupled Quasi-2D Dusty Plasmas.

PMID- 10062868
TI  - Spherical Stellarator Configuration.

PMID- 10062869
TI  - Model for Melt Fracture Instabilities in the Capillary Flow of Polymer Melts.

PMID- 10062870
TI  - Neutron Scattering Evidence for Localized Soft Modes in Amorphous Polymers.

PMID- 10062871
TI  - Identity of InSb-II and InSb-III.

PMID- 10062872
TI  - Measurement of MeV Ion Track Structure in an Organic Solid.

PMID- 10062873
TI  - Simulation of Fracturing Reinforced Polymer Blends.

PMID- 10062874
TI  - Phonons in Glasses: Numerical Simulations and Phenomenological Theory.

PMID- 10062876
TI  - Stick-Slip Motion and Force Fluctuations in a Driven Two-Wave Potential.

PMID- 10062875
TI  - Generalized Dynamic Scaling for Critical Relaxations.

PMID- 10062877
TI  - Structure and Stability of Si(114)-(2 x 1).

PMID- 10062879
TI  - Inhibited Al Diffusion and Growth Roughening of Ga-Coated Al(100).

PMID- 10062878
TI  - Scanning Tunneling Microscopy Study of InP(100)-(2 x 4): An Exception to the
      Dimer Model.

PMID- 10062880
TI  - Formation of Ion Irradiation-Induced Small-Scale Defects on Graphite Surfaces.

PMID- 10062881
TI  - Anisotropy in the Adsorption of H2O at Low Coordination Sites on Pt(111).

PMID- 10062882
TI  - Liouville Theory as a Model for Prelocalized States in Disordered Conductors.

PMID- 10062883
TI  - Spin Waves throughout the Brillouin Zone of a Double-Exchange Ferromagnet.

PMID- 10062884
TI  - Direct Observation of Lattice Polaron Formation in the Local Structure of La1
      xCaxMnO3.

PMID- 10062886
TI  - Occurrence of d-Wave Pairing in the Phonon-Mediated Mechanism of High Temperature
      Superconductivity in Cuprates.

PMID- 10062885
TI  - Parametric Excitation of Edge Waves in the Quantum Hall Effect.

PMID- 10062887
TI  - Superconducting Gap Anisotropy vs Doping Level in High-Tc Cuprates.

PMID- 10062888
TI  - Fine Structure in a High-Resolution Vortex Dissipation Study of YBa2 Cu3O7-
      delta.

PMID- 10062889
TI  - a-b Plane Microwave Surface Impedance of a High-Quality Bi2Sr2CaCu2O8 Single
      Crystal.

PMID- 10062890
TI  - Phase Diagram for a Magnetic Thin Film with Dipolar Interactions and Magnetic
      Surface Anisotropy.

PMID- 10062891
TI  - Surface Magnetism of Ultrathin gamma -Fe Films Investigated by Nonlinear Magneto
      optical Kerr Effect.

PMID- 10062893
TI  - X-Ray Scattering Study of the Magnetic Structure near the (001) Surface of UO2.

PMID- 10062892
TI  - Resonant Surface Magnetic X-Ray Diffraction from Co3Pt(111).

PMID- 10062894
TI  - Tunneling States and Resonant Light Interaction in an Oxide Glass.

PMID- 10062895
TI  - Optical Properties of Ordered As Layers on InP(110) Surfaces.

PMID- 10062896
TI  - Influence of Quantum Confinement on the Critical Points of the Band Structure of
      Si.

PMID- 10062897
TI  - Links, Knots, and Knotted Labyrinths in Bistable Systems.

PMID- 10062899
TI  - Traveling-Wave Chemotaxis.

PMID- 10062898
TI  - Scaling of the Dynamic Scattering Function of Concentrated Colloidal Suspensions.

PMID- 10062900
TI  - Magic Numbers in Protein Structures.

PMID- 10062901
TI  - Polymer Translocation through a Pore in a Membrane.

PMID- 10062902
TI  - Comment on: "Breathers and Kink-Antikink Nucleation"

PMID- 10062903
TI  - Buttiker and Christen Reply.

PMID- 10062908
TI  - Error Correcting Codes in Quantum Theory.

PMID- 10062909
TI  - There is No Quantum Regression Theorem.

PMID- 10062910
TI  - Holographic Manipulation of a Cold Atomic Beam.

PMID- 10062911
TI  - C-caronerenkov Radiation by Neutrinos in a Supernova Core.

PMID- 10062913
TI  - Nonperturbative Study of Generalized Ladder Graphs in a Phi 2 chi Theory.

PMID- 10062914
TI  - Partial Dynamical Symmetry in Deformed Nuclei.

PMID- 10062912
TI  - Observation of an Excited Charmed Baryon Decaying into Xi 0c pi +

PMID- 10062915
TI  - Reducibility and Thermal and Mass Scaling in Angular Correlations from
      Multifragmentation Reactions.

PMID- 10062917
TI  - Simultaneous Measurement of Recoil Velocity and Alignment of S(1D2) Atoms in
      Photodissociation of OCS.

PMID- 10062916
TI  - Direct Observation of the Spontaneous Emission of the Hyperfine Transition F=4 to
      F=3 in Ground State Hydrogenlike 165Ho66+ in an Electron Beam Ion Trap.

PMID- 10062918
TI  - Freedom and Constraints of a Metal Atom Encapsulated in Fullerene Cages.

PMID- 10062919
TI  - Quantum Chaos in Terms of Entropy for Periodically Kicked Top.

PMID- 10062920
TI  - Asymmetry of Operation and Energy Trapping in a Superradiant Laser.

PMID- 10062921
TI  - Experimental Determination of the Long-Range Potential of Argon Pairs by Means of
      Small-Angle Neutron Diffraction.

PMID- 10062922
TI  - Demonstration of Laser Induced X-Ray Generation in an Expanding Laser Produced
      Plasma.

PMID- 10062923
TI  - Suppression of Rayleigh-Taylor Instability in Z-Pinch Loads with Tailored Density
      Profiles.

PMID- 10062924
TI  - Many-Wave Light Scattering Features in Blue-Phase Kossel Diagrams and the Phase
      Problem.

PMID- 10062925
TI  - Core Structure of Thermal Donors in Silicon.

PMID- 10062926
TI  - Shallow Thermal Donor Defects in Silicon.

PMID- 10062927
TI  - Dynamics of Brittle Fracture with Variable Elasticity.

PMID- 10062928
TI  - Critical Equation of State from the Average Action.

PMID- 10062929
TI  - Gap Independence and Lacunarity in Percolation Clusters.

PMID- 10062930
TI  - Chlorine on Si(001)-(2 x 1): Bridge versus Terminal Bonding.

PMID- 10062931
TI  - Magic Size Effects for Heteroepitaxial Island Diffusion.

PMID- 10062932
TI  - Spatial Period-Doubling Instability of Dendritic Arrays in Directional
      Solidification.

PMID- 10062933
TI  - Thermodynamic Properties of the Planar t-J Model.

PMID- 10062934
TI  - Directed Beam of Excitons Produced by Stimulated Scattering.

PMID- 10062935
TI  - Excitonic Instability and Electric-Field-Induced Phase Transition Towards a Two
      Dimensional Exciton Condensate.

PMID- 10062936
TI  - Polaron Ordering in Low-Doping La1-x SrxMnO3.

PMID- 10062938
TI  - Long-Range Correlations in the Wave Functions of Chaotic Systems.

PMID- 10062937
TI  - Unexpected Negative Exchange Splitting of the Fe(001) Image State.

PMID- 10062940
TI  - Electron Photoinjection from Silicon to Ultrathin SiO2 Films via Ambient Oxygen.

PMID- 10062939
TI  - Enhanced Spin Dependent Scattering at Interfaces.

PMID- 10062941
TI  - Probing the Superconducting Proximity Effect in NbSe2 by Scanning Tunneling
      Microscopy.

PMID- 10062942
TI  - c-Axis Conductivity and Intrinsic Josephson Effects in YBa2Cu3O7- delta.

PMID- 10062944
TI  - Reversible Magnetization of Irradiated High-Tc Superconductors.

PMID- 10062943
TI  - Dimensional Crossover for Intrinsic dc Josephson Effect in Bi2Sr2CaCu2O8 2212
      Single Crystal Whiskers.

PMID- 10062945
TI  - Quantum Critical Behavior for a Model Magnet.

PMID- 10062947
TI  - Probing the Highly Correlated Mixed-Valent State via Charge Transfer with Atoms
      Moving Out from a Surface.

PMID- 10062946
TI  - Discovery of 90 degrees Magneto-optical Polar Kerr Rotation in CeSb.

PMID- 10062948
TI  - Observation of a Mesostructure in Calcium Silicate Hydrate Gels of Portland
      Cement.

PMID- 10062949
TI  - Wall-Slip and Polymer-Melt Flow Instability.

PMID- 10062950
TI  - Field Theory of Electromagnetic Brain Activity.

PMID- 10062952
TI  - Synchronization by Disorder in Coupled Systems.

PMID- 10062951
TI  - Decoherence in Ion Trap Quantum Computers.

PMID- 10062953
TI  - Slip Complexity in a Crustal-Plane Model of an Earthquake Fault.

PMID- 10062954
TI  - Comment on "Flux Quantization in Magnetic Nanowires Imaged by Electron
      Holography"

PMID- 10062955
TI  - Comment on "Flux Quantization in Magnetic Nanowires Imaged by Electron
      Holography"

PMID- 10062956
TI  - Beeli, Doudin, and Stadelmann Reply.

PMID- 10062958
TI  - Haussmann and Dohm Reply.

PMID- 10062957
TI  - Comment on "Heat-Flow Induced Anomalies in Superfluid 4He near T lambda "

PMID- 10062961
TI  - Adiabatic Measurements on Metastable Systems.

PMID- 10062962
TI  - Collective Excitations of a Bose-Einstein Condensate in a Magnetic Trap.

PMID- 10062963
TI  - Topology of the Support of the Two-Dimensional Lattice Random Walk.

PMID- 10062964
TI  - Self-Consistent Ornstein-Zernike Approximation for Lattice Gases.

PMID- 10062966
TI  - Zero-Brane Quantum Mechanics.

PMID- 10062965
TI  - Possible Clustering of the Most Energetic Cosmic Rays within a Limited Space
      Angle Observed by the Akeno Giant Air Shower Array.

PMID- 10062967
TI  - Nucleon Strangeness Content through Vector Meson Dominance.

PMID- 10062968
TI  - Measurement of the p

PMID- 10062969
TI  - Momentum Content of Single-Nucleon Halos.

PMID- 10062970
TI  - Single-neutron states in 133Sn.

PMID- 10062971
TI  - Fully Differential Cross Sections for Double Photoionization of He Measured by
      Recoil Ion Momentum Spectroscopy.

PMID- 10062972
TI  - Annihilation Dynamics of Positrons in Molecular Environments: Theoretical Study
      of Low-Energy Positron-C2 H4 Scattering.

PMID- 10062974
TI  - Enhanced Isotope Discrimination Using Electromagnetically Induced Transparency.

PMID- 10062973
TI  - Experimental Observation of Spontaneous Emission Cancellation.

PMID- 10062975
TI  - Inhibition and Enhancement of Two Photon Absorption.

PMID- 10062976
TI  - Dynamics of Dispersive and Nonlinear Media.

PMID- 10062977
TI  - Order Parameter for the Transition from Phase to Amplitude Turbulence.

PMID- 10062978
TI  - Diffusion due to Beam-Beam Interaction and Fluctuating Fields in Hadron
      Colliders.

PMID- 10062979
TI  - Electron Temperature Measurements of Solid Density Plasmas Produced by Intense
      Ultrashort Laser Pulses.

PMID- 10062980
TI  - Surface Holography by Angle-Resolved Electron-Energy-Loss Spectroscopy.

PMID- 10062982
TI  - Novel Monte Carlo Approach to the Dynamics of Fluids: Single-Particle Diffusion,
      Correlation Functions, and Phase Ordering of Binary Fluids.

PMID- 10062981
TI  - Theoretical Scanning Tunneling Microscopy Images of the As Vacancy on the
      GaAs(110) Surface.

PMID- 10062983
TI  - Low-Temperature Thermodynamic and Thermal-Transport Properties of Decagonal
      Al65Cu20Co15.

PMID- 10062984
TI  - Observation of Atomlike Nitrogen in Nitrogen-Implanted Solid C60.

PMID- 10062985
TI  - Pressure-Temperature Phase Diagram of the Spin-Peierls Compound CuGeO3.

PMID- 10062986
TI  - Critical Adsorption at the Free Surface of a Smectic Liquid Crystal Possessing a
      Second-Order Phase Transition.

PMID- 10062987
TI  - Site Exchange of Ge and Sb on Si(100) during Surfactant-Mediated Epitaxial
      Growth.

PMID- 10062989
TI  - Anisotropy of Growth of the Close-Packed Surfaces of Silver.

PMID- 10062988
TI  - Size Scaling in the Decay of Metastable Structures.

PMID- 10062990
TI  - Quantum Monte Carlo Calculations of the Energy of the Relativistic Homogeneous
      Electron Gas.

PMID- 10062991
TI  - Determination of the Critical Conductivity Exponent for the Metal-Insulator
      Transition at Nonzero Temperatures: Universality of the Transition.

PMID- 10062993
TI  - Pressure Dependence of Hole-Mn and Mn-Mn Exchange Interactions in Cd0.95Mn0.05Se.

PMID- 10062992
TI  - Optical Coherence in Semiconductors: Strong Emission Mediated by Nondegenerate
      Interactions.

PMID- 10062994
TI  - Generalization of Thermal Conductivity and Lorenz Number to Hot-Carrier
      Conditions in Nondegenerate Semiconductors.

PMID- 10062995
TI  - Quantum Steering Effects in the Dissociative Adsorption of H2 on Rh(100).

PMID- 10062996
TI  - Mesoscopic Fluctuations in the Ground State Energy of Disordered Quantum Dots.

PMID- 10062997
TI  - Electronic Shell Structure and Relative Abundances of Cesium-Coated C60.

PMID- 10062998
TI  - Terahertz Dynamics of Excitons in GaAs/AlGaAs Quantum Wells.

PMID- 10062999
TI  - Observation of Internal Transitions of Confined Excitons in GaAs/AlGaAs Quantum
      Wells.

PMID- 10063001
TI  - Phonon Emission from a 2D Electron Gas: Evidence of Transition to the
      Hydrodynamic Regime.

PMID- 10063000
TI  - Zeeman Splitting of the Coulomb Anomaly: A Tunneling Study in Two Dimensions.

PMID- 10063002
TI  - Increased "Bulk" NiO Resistivity in Fe3/NiO Modulated Structures as a Function of
      Modulation Wavelength.

PMID- 10063003
TI  - Phonon Softening and Superconductivity in Tellurium under Pressure.

PMID- 10063004
TI  - Local Electrodynamics in Heavy Ion Irradiated Bi2Sr2CaCu 2O8+ delta.

PMID- 10063005
TI  - Unusual Electric Field Effects in Nd0.7Sr0.3MnO3.

PMID- 10063006
TI  - Collective Theory for Surface Enhanced Raman Scattering.

PMID- 10063007
TI  - Interference between Bulk and Surface Photoemission Transitions in Ag(111).

PMID- 10063008
TI  - Speed of Fronts of the Reaction-Diffusion Equation.

PMID- 10063010
TI  - Nuclear Magnetic Resonance Measurements of Diffusion in Granular Media.

PMID- 10063009
TI  - Experimental Determination of the Dispersion Relation for Spiral Waves.

PMID- 10063011
TI  - Infinite Series of Exact Equations in the Bak-Sneppen Model of Biological
      Evolution.

PMID- 10063013
TI  - Comment on "Thermoelectric Power: A Simple, Instructive Probe of High-Tc
      Superconductors"

PMID- 10063012
TI  - Theoretical Approach to Identify Carcinogenic Activity of Polycyclic Aromatic
      Hydrocarbons.

PMID- 10063014
TI  - Tallon et al. Reply.

PMID- 10063015
TI  - Stability Criterion for Dark Solitons.

PMID- 10063016
TI  - Long Time Asymptotics for Quantum Particles in a Periodic Potential.

PMID- 10063017
TI  - Onsager Reciprocity Relations without Microscopic Reversibility.

PMID- 10063018
TI  - Common Trends in the Critical Behavior of the Ising and Directed Walk Models.

PMID- 10063019
TI  - Conversion of Neutron Stars to Strange Stars as a Possible Origin of gamma -Ray
      Bursts.

PMID- 10063020
TI  - Zero Temperature Chiral Phase Transition in SU(N) Gauge Theories.

PMID- 10063021
TI  - Proposal for Detecting Top Spin Correlation Effects at the Fermilab Tevatron.

PMID- 10063022
TI  - Nuclear Gluon Shadowing via Continuum Lepton Pairs in p+A at sqrt s=200A GeV.

PMID- 10063023
TI  - Amplification of Pionic Instabilities in High-Energy Collisions?

PMID- 10063024
TI  - Heating of Nuclei with Energetic Antiprotons.

PMID- 10063025
TI  - Attosecond Pulse Trains Using High-Order Harmonics.

PMID- 10063026
TI  - Molecular Ion Geometries from Inversion of Coulomb Explosion Imaging Data.

PMID- 10063028
TI  - Analysis of Collision Induced Dissociation of Na2+ Molecular Ions.

PMID- 10063027
TI  - Double Ionization of Helium and Neon for Fast Heavy-Ion Impact: Correlated Motion
      of Electrons from Bound to Continuum States.

PMID- 10063029
TI  - Near-Threshold Ionization of He and H2 by Positron Impact.

PMID- 10063030
TI  - Tachyonlike Excitations in Inverted Two-Level Media.

PMID- 10063031
TI  - Linear Response of Hamiltonian Chaotic Systems as a Function of the Number of
      Degrees of Freedom.

PMID- 10063032
TI  - Growth of Noninfinitesimal Perturbations in Turbulence.

PMID- 10063033
TI  - Measured Velocity Boundary Layers in Turbulent Convection.

PMID- 10063034
TI  - Practical Kinetic Model for Hard Sphere Dynamics.

PMID- 10063035
TI  - Faraday Wave Turbulence on a Spherical Liquid Shell.

PMID- 10063036
TI  - Stimulated Brillouin Scattering in Multispecies Laser-Produced Plasmas.

PMID- 10063037
TI  - Electromagnetic Beam Breakup: Multiple Filaments, Single Beam Equilibria, and
      Radiation.

PMID- 10063038
TI  - Enhanced Radio Frequency Field Penetration in an Inductively Coupled Plasma.

PMID- 10063039
TI  - Wide Solitons in an Ion-Beam-Plasma System.

PMID- 10063041
TI  - Laser Beam Deflection Induced by Transverse Plasma Flow.

PMID- 10063040
TI  - First Optical Observation of Intensity Dependent Laser Beam Deflection in a
      Flowing Plasma.

PMID- 10063042
TI  - Anomalous Isotope Effect in the Relaxation of the SD and SH Vibrational Stretch
      Modes in Amorphous As2S3.

PMID- 10063043
TI  - Dopant Segregation at Semiconductor Grain Boundaries through Cooperative Chemical
      Rebonding.

PMID- 10063044
TI  - Domain-Wall Scaling Study of the Structural Glass Transition.

PMID- 10063045
TI  - Nonlinear Spin Dynamics and Magnetic Field Distortion of the Superfluid 3He-B
      Order Parameter.

PMID- 10063046
TI  - Evidence for Size Effects on Interfacial Widths in Confined Thin Films.

PMID- 10063048
TI  - Dimer and String Formation during Low Temperature Silicon Deposition on Si(100).

PMID- 10063047
TI  - Evidence for the Tunneling Site on Transition-Metal Oxides: TiO2(110).

PMID- 10063049
TI  - Morphological Evolution of Strained Films by Cooperative Nucleation.

PMID- 10063051
TI  - Direct Observation of the Crossover from Single to Multiple Excitations in
      Femtosecond Surface Photochemistry.

PMID- 10063050
TI  - Atom Movement and Binding on Surface Clusters: Pt on Pt(111) Clusters.

PMID- 10063052
TI  - Exact Results for a 1D Kondo Lattice from Bosonization.

PMID- 10063053
TI  - Inelastic X-Ray Scattering as a Probe of the Many-Body Local-Field Factor in
      Metals.

PMID- 10063054
TI  - Hall-Velocity Limited Magnetoconductivity in a Classical Two-Dimensional Wigner
      Crystal.

PMID- 10063055
TI  - Two-Electron State in a Disordered 2D Island: Pairing Caused by the Coulomb
      Repulsion.

PMID- 10063056
TI  - Charge Density Wave Behavior in the Integer Quantum Hall Effect Edge States.

PMID- 10063057
TI  - Reversible Manipulations of Room Temperature Mechanical and Quantum Transport
      Properties in Nanowire Junctions.

PMID- 10063059
TI  - Transitions in the Vortex Lattice in YBa2Cu3O7- delta Single Crystal.

PMID- 10063058
TI  - Magneto-Coulomb Drag: Interplay of Electron-Electron Interactions and Landau
      Quantization.

PMID- 10063060
TI  - Odd-Parity Superconductivity with Parallel Spin Pairing in UPt3: Evidence from
      195Pt Knight Shift Study.

PMID- 10063061
TI  - Hole Doping of the CuO2 Chains in (La,Sr,Ca)14Cu24O41.

PMID- 10063062
TI  - Spin-Density-Wave Antiferromagnetism of Cr in Fe/Cr(001) Superlattices.

PMID- 10063063
TI  - Probing the Spin-Spin Dynamical Autocorrelation Function in a Spin Glass above Tg
      via Muon Spin Relaxation.

PMID- 10063064
TI  - Shadow Band in the One-Dimensional Infinite-U Hubbard Model.

PMID- 10063066
TI  - Stochastic Analysis of Limit Cycle Behavior in Spatially Extended Systems.

PMID- 10063065
TI  - Theory of Coupled First-Order Phase Transformations: Application to Bainitic
      Transformations.

PMID- 10063068
TI  - Multibranch Entrainment and Scaling in Large Populations of Coupled Oscillators.

PMID- 10063067
TI  - Rotationally Inelastic Scattering of C2H2 from LiF(100): Translational Energy
      Dependence.

PMID- 10063069
TI  - Comment on "Energy Dependence of Electron Lifetime in Graphite Observed with
      Femtosecond Photoemission Spectroscopy"

PMID- 10063070
TI  - Xu et al. Reply.

PMID- 10063072
TI  - Separability Criterion for Density Matrices.

PMID- 10063073
TI  - Laser-Driven Collisions between Atoms in a Bose-Einstein Condensed Gas.

PMID- 10063074
TI  - Survival Probability of a Gaussian Non-Markovian Process: Application to the T=0
      Dynamics of the Ising Model.

PMID- 10063075
TI  - Black Hole Criticality in the Brans-Dicke Model.

PMID- 10063076
TI  - Superfluidity in beta -Stable Neutron Star Matter.

PMID- 10063077
TI  - The Gravitational Constant, the Chandrasekhar Limit, and Neutron Star Masses.

PMID- 10063078
TI  - High Energy Processes in Clusters of Galaxies and the Origin of Cosmic Rays.

PMID- 10063079
TI  - Measurement of Lambda 0b Lifetime Using Lambda 0b--> Lambda +c

PMID- 10063080
TI  - Shell Model Monte Carlo Studies of gamma -Soft Nuclei.

PMID- 10063081
TI  - Pre-Equilibrium Effects in the Population of Giant Dipole Resonances.

PMID- 10063082
TI  - Observation of Hollow Atoms or Ions above Insulator and Metal Surfaces.

PMID- 10063083
TI  - Optical Activity of Anisotropic Achiral Surfaces.

PMID- 10063084
TI  - Long-Range Predissociation in Two-Color Photoassociation of Ultracold Na Atoms.

PMID- 10063085
TI  - Measurement of the van der Waals Force in an Atomic Mirror.

PMID- 10063086
TI  - Self-Organization, Broken Symmetry, and Lasing in an Atomic Vapor: The
      Interdependence of Gratings and Gain.

PMID- 10063087
TI  - Gutzwiller's Trace Formula and Spectral Statistics: Beyond the Diagonal
      Approximation.

PMID- 10063089
TI  - Couette-Taylor Flow in a Dilute Polymer Solution.

PMID- 10063088
TI  - Energy Extraction and Achievement of the Saturation Limit in a Discharge-Pumped
      Table-Top Soft X-Ray Amplifier.

PMID- 10063090
TI  - q Divergence of Nonequilibrium Fluctuations and Its Gravity-Induced Frustration
      in a Temperature Stressed Liquid Mixture.

PMID- 10063092
TI  - Stimulated Coherent Emission from Short Electron Bunches in Free Space.

PMID- 10063091
TI  - Asymmetry of Velocity Increments in Fully Developed Turbulence and the Scaling of
      Low-Order Moments.

PMID- 10063093
TI  - Observation of Two Ion-Acoustic Waves in a Two-Species Laser-Produced Plasma with
      Thomson Scattering.

PMID- 10063094
TI  - Double-Cross Instability: An Absolute Instability Caused by Counter-Propagating
      Positive- and Negative-Energy Waves.

PMID- 10063095
TI  - Equilibrium and Fluctuations in a Plasma Confined in a Pure Toroidal Field.

PMID- 10063096
TI  - Polarized X-ray Fluorescence as a Probe of Ground State Properties.

PMID- 10063097
TI  - Phase Separation in Nearly Symmetric Polymer Mixtures.

PMID- 10063098
TI  - Structure, Barriers, and Relaxation Mechanisms of Kinks in the 90 degrees Partial
      Dislocation in Silicon.

PMID- 10063099
TI  - Elastic Theory Has Zero Radius of Convergence.

PMID- 10063101
TI  - Microscopic Explanation of the Non-Arrhenius Conductivity in Glassy Fast Ionic
      Conductors.

PMID- 10063100
TI  - Critical Diffusivity in Restricted Geometry: Decoupled Mode Approximation.

PMID- 10063102
TI  - Experimental Observation of Critical Wetting.

PMID- 10063103
TI  - Dewetting Modes of Thin Metallic Films: Nucleation of Holes and Spinodal
      Dewetting.

PMID- 10063104
TI  - hcp and bcc Cu and Pd Films.

PMID- 10063105
TI  - Studies of Charged Excitations in pi -Conjugated Oligomers and Polymers by
      Optical Modulation.

PMID- 10063106
TI  - Electron-Exchange Processes in the Excitations of NiO(100) Surface d States.

PMID- 10063107
TI  - Crossover from Critical Orthogonal to Critical Unitary Statistics at the Anderson
      Transition.

PMID- 10063108
TI  - Level Statistics and Localization for Two Interacting Particles in a Random
      Potential.

PMID- 10063109
TI  - Local Isoelectronic Reactivity of Solid Surfaces.

PMID- 10063110
TI  - Charged "Few-Electron-Single Spatially Separated Hole" Complexes in a Double
      Quantum Well near a Metal Plate.

PMID- 10063111
TI  - A First-Landau-Level Laughlin/Jain Wave Function for the Fractional Quantum Hall
      Effect.

PMID- 10063112
TI  - Internal Excitations and Dissipative Damping of Quantum Hall Skyrmions.

PMID- 10063113
TI  - Quantized Hall Currents in the High Field Phase of alpha -(BEDT-TTF)2TlHg(SCN)4.

PMID- 10063114
TI  - Giant Magnetoresistive Effects in a Single Element Magnetic Thin Film.

PMID- 10063115
TI  - Hall Voltage Fluctuations as a Diagnostic of Internal Magnetic Field Fluctuations
      in High Temperature Superconductors and the Half-Filled Landau Level.

PMID- 10063116
TI  - Effect of Disorder on the Vortex-Lattice Melting Transition.

PMID- 10063117
TI  - Vortex-Loop Unbinding and Flux-Line Lattice Melting in Superconductors.

PMID- 10063119
TI  - Evidence for Extreme Gap Anisotropy in Ho0.1Y0.9Ba2Cu3O7 from Neutron
      Spectroscopy of Ho3+

PMID- 10063118
TI  - Plastic Vortex Creep in YBa2Cu3O7-x Crystals.

PMID- 10063120
TI  - New Magnetic Coherence Effect in Superconducting La2-xSrxCuO4.

PMID- 10063121
TI  - Tricritical Behavior of Ising Spin Glasses with Charge Fluctuations.

PMID- 10063122
TI  - Two-Channel Kondo Lattice: An Incoherent Metal.

PMID- 10063123
TI  - Experimental Evidence of a Haldane Gap in an S=2 Quasi-Linear-Chain
      Antiferromagnet.

PMID- 10063124
TI  - Braids Plaited by Magnetic Holes.

PMID- 10063126
TI  - Giant Permittivity in Epitaxial Ferroelectric Heterostructures.

PMID- 10063125
TI  - Magnetic Frustration Induced Formation of the Spin-Peierls Phase in CuGeO3:
      Experimental Evidence.

PMID- 10063127
TI  - Observation of Interband Two-Photon Absorption Saturation in CdS.

PMID- 10063128
TI  - New Evidence for Localized Electronic States on Atomically Sharp Field Emitters.

PMID- 10063130
TI  - Power-Law Distributions in Some Random Boolean Networks.

PMID- 10063129
TI  - Competing Reactions with Initially Separated Components.

PMID- 10063131
TI  - Vibrational Echo Studies of Protein Dynamics.

PMID- 10063133
TI  - Comment on "Quantum Phase of Induced Dipoles Moving in a Magnetic Field"

PMID- 10063132
TI  - Adhesion of Membranes via Anchored Stickers.

PMID- 10063135
TI  - Comment on "Fixed-Point Structure of Scalar Fields"

PMID- 10063134
TI  - Wei et al. Reply.

PMID- 10063136
TI  - Halpern and Huang Reply.

PMID- 10063137
TI  - Comment on "Raman Modes of 6H Polytype of Silicon Carbide to Ultrahigh Pressures"

PMID- 10063138
TI  - Liu and Vohra Reply.

PMID- 10063139
TI  - Salty Water Cerenkov Detectors for Solar Neutrinos

PMID- 10063140
TI  - Atom de Broglie Wave Deflection by a Single Cavity Mode in the Few-Photon Limit:
      Quantum Prism.

PMID- 10063141
TI  - Collective Excitations of a Confined Bose Condensate.

PMID- 10063142
TI  - Collective Excitations of Atomic Bose-Einstein Condensates.

PMID- 10063143
TI  - Cellular Automaton Model for Random Walkers.

PMID- 10063144
TI  - Riemannian Geometrical Analysis of the Motion of a Vortex Filament: A System of C

PMID- 10063146
TI  - A New Test of Inflation.

PMID- 10063145
TI  - Solar Neutrino Data Covering Solar Cycle 22.

PMID- 10063147
TI  - Photon Splitting in a Very Strong Magnetic Field.

PMID- 10063148
TI  - Photon Splitting in a Strong Magnetic Field: Recalculation and Comparison with
      Previous Calculations.

PMID- 10063149
TI  - Horizontal Symmetry for Quark and Squark Masses in Supersymmetric SU(5).

PMID- 10063150
TI  - J/ psi Suppression in Pb-Pb Collisions: A Hint of Quark-Gluon Plasma Production?

PMID- 10063151
TI  - Fragmentation of the Decay from the Superdeformed Yrast Band in 192Hg.

PMID- 10063153
TI  - QED Corrections of O(mc2 alpha 7 ln alpha ) to the Fine Structure Splittings of
      Helium and He-like Ions.

PMID- 10063152
TI  - Spin-Dependent Triaxial Deformation in Neutron-Rich Mo Isotopes.

PMID- 10063154
TI  - Critical Analysis of Non-Nuclear Electron-Density Maxima and the Maximum Entropy
      Method.

PMID- 10063156
TI  - Atomic Transport in an Optical Lattice: An Investigation through Polarization
      Selective Intensity Correlations.

PMID- 10063155
TI  - Differential Double Ionization of He by Compton Photons and Charged Particles at
      Large Energy Transfers.

PMID- 10063157
TI  - Spatial Mode Control of High-Order Harmonics.

PMID- 10063158
TI  - Measurement of Charge Exchange between H2 and Low-Energy Ions with Charge States
      35 <~ q <~ 80.

PMID- 10063159
TI  - Field Commutation Relations in Optical Cavities.

PMID- 10063160
TI  - Nonadiabatic Effects in High-Harmonic Generation with Ultrashort Pulses.

PMID- 10063161
TI  - Experimental Demonstration of Antimonotonicity: The Concurrent Creation and
      Destruction of Periodic Orbits in a Driven Nonlinear Electronic Resonator.

PMID- 10063162
TI  - Intermittent Loss of Synchronization in Coupled Chaotic Oscillators: Toward a New
      Criterion for High-Quality Synchronization.

PMID- 10063164
TI  - Long Internal Waves of Finite Amplitude.

PMID- 10063163
TI  - Experimental Determination of a Topological Invariant in a Pattern of Optical
      Singularities.

PMID- 10063166
TI  - Hybrid Simulation of the Nonlinear Evolution of a Collisionless, Large Larmor
      Radius Z Pinch.

PMID- 10063165
TI  - Spin Flipping through an Intrinsic Depolarizing Resonance by Strengthening It.

PMID- 10063167
TI  - Observation of an Opticlike Phase Mode in an Antiferroelectric Liquid Crystal.

PMID- 10063168
TI  - Kinetics and Jamming Coverage in a Random Sequential Adsorption of Polymer
      Chains.

PMID- 10063169
TI  - Electronic Structure of Icosahedral Alloys Studied by Ultrahigh Energy Resolution
      Photoemission Spectroscopy.

PMID- 10063170
TI  - "Hidden" High-to-Low Cristobalite Type Transition in HgSe and HgTe at High
      Pressure.

PMID- 10063172
TI  - Order-Parameter Relaxation Times of Finite Three-Dimensional Ising-like Systems.

PMID- 10063171
TI  - Network Approach to Void Percolation in a Pack of Unequal Spheres.

PMID- 10063173
TI  - Heat Capacity Anomalies of Superfluid 4He under the Influence of a Counterflow
      near T lambda.

PMID- 10063174
TI  - Film/Substrate Orientation Relationship in the AlN/6H-SiC Epitaxial System.

PMID- 10063175
TI  - Direct Measurements of Free Crystal Growth in Deeply Undercooled Melts of
      Semiconducting Materials.

PMID- 10063176
TI  - First-Principles Calculation of the Anomalous Perpendicular Anisotropy in a Co
      Monolayer on Au(111).

PMID- 10063177
TI  - Momentum-Dependent Charge Transfer Excitations in Sr2CuO 2Cl2 Angle-Resolved
      Electron Energy Loss Spectroscopy.

PMID- 10063178
TI  - Evidence for a Bilayer Quantum Wigner Solid.

PMID- 10063179
TI  - Magnetoresistance of Two-Dimensional Fermions in a Random Magnetic Field.

PMID- 10063180
TI  - Solution of an ac Kondo Model.

PMID- 10063181
TI  - Destruction of Conductance Fluctuations in a Dirty Wire.

PMID- 10063182
TI  - Giant Optical Anisotropy of Semiconductor Heterostructures with No Common Atom
      and the Quantum-Confined Pockels Effect.

PMID- 10063183
TI  - New Class of Resonances at the Edge of the Two Dimensional Electron Gas.

PMID- 10063184
TI  - Coexistence of Superconductivity and Localization in Bi2Sr2(Caz,Pr1-z)Cu2O8+y.

PMID- 10063185
TI  - Theory of Scanning Tunneling Microscopy Probe of Impurity States in a D-Wave
      Superconductor.

PMID- 10063186
TI  - Glassy Motion of Elastic Manifolds.

PMID- 10063187
TI  - Nonmagnetic Impurity Scattering in a dx2-y 2 Superconductor near a Van Hove
      Point: Zn versus Ni in the Cuprates.

PMID- 10063188
TI  - Optical Conductivity of High Tc Superconductors: From Underdoped to Overdoped.

PMID- 10063189
TI  - Possible Origin for Oscillatory Superconducting Transition Temperature in
      Superconductor/Ferromagnet Multilayers.

PMID- 10063190
TI  - NMR Evidence for a Magnetic Soliton Lattice in the High-Field Phase of CuGeO.

PMID- 10063191
TI  - Monte Carlo Study of Correlations in Quantum Spin Ladders.

PMID- 10063193
TI  - Nucleation of Magnetization Reversal in Individual Nanosized Nickel Wires.

PMID- 10063192
TI  - Ferromagnetic Ordering and Unusual Magnetic Ion Dynamics in La0.67Ca0.33MnO3.

PMID- 10063194
TI  - Frequency Shifts of the Internal Phonon Modes in La0.7Ca0.3MnO3.

PMID- 10063195
TI  - Singlet Intrachain Exciton Generation and Decay in Poly (p-phenylenevinylene).

PMID- 10063196
TI  - Conditions of Elaboration of Luminescent Porous Silicon from Hydrogenated
      Amorphous Silicon.

PMID- 10063197
TI  - Local Excitation, Scattering, and Interference of Surface Plasmons.

PMID- 10063198
TI  - Diabatic Energy Level Confluence: The Mechanism of Negative Ion Conversion of
      Neutral Atoms in Grazing Scattering from Insulator Surfaces.

PMID- 10063199
TI  - When Like Charges Attract: The Effects of Geometrical Confinement on Long-Range
      Colloidal Interactions.

PMID- 10063200
TI  - Optimal Protein Design Procedure.

PMID- 10063201
TI  - Large Amplitude Elastic Motions in Proteins from a Single-Parameter, Atomic
      Analysis.

PMID- 10063202
TI  - Random Secretion of Growth Hormone in Humans.

PMID- 10063204
TI  - Current bibliography of the history of science and its cultural influences. 1998.

PMID- 10063205
TI  - Follow-up of clinical efficacy of iontophoresis therapy for postherpetic
      neuralgia (PHN).
AB  - A great variety of therapies have been attempted for PHN, including
      pharmacotherapy and physical therapy. However, there has been no decisive
      treatment, and reports of the clinical efficacy of all available therapies have
      been rather controversial. Almost all studies conducted so far have looked only
      at short-term therapeutic efficacy, and only a few investigators have conducted
      long-term observations or studies on long-term outcome. We followed up the
      clinical efficacy of iontophoresis therapy using lidocaine and methylprednisolone
      in 197 PHN patients. Monitoring conducted for an average of 4 years after
      completion of the treatment showed that pain remained unchanged or improved
      compared to pain observed upon completion of the treatment in 90.4% of patients.
      Although 42.6% of patients were still continuing some treatment, 90.9% were found
      to be able to take care of themselves. Findings obtained were reviewed and
      discussed from various viewpoints. Our findings showed that iontophoresis therapy
      is not only effective at the end of the treatment, but its efficacy is maintained
      over a long period of time, indicating that it is clinically very useful for the
      treatment of PHN.

PMID- 10063206
TI  - Topical tocoretinate improved hypertrophic scar, skin sclerosis in systemic
      sclerosis and morphea.
AB  - Four patients with systemic scleroderma (SSc), 4 patients with morphea, and 4
      patients with hypertrophic scar were treated with topical tocoretinate for 6
      months to 3 years and studied clinically and histopathologically. Clinically, all
      of the lesions responded to this therapy. The stiffness of the skin lesions,
      glossy appearance of the lesions, and telangiectasia improved.
      Histopathologically, the proliferated collagen fibers decreased in thickness, and
      the inter-fiber spaces increased. Immunoreactive tenascin-C expressed in the
      proliferated deep dermal fibers of the SSc and hypertrophic scar lesions was
      markedly decreased compared with the level before the topical tocoretinate
      therapy. Topical tocoretinate has been used for the treatment of ulcers; it is
      also a potent treatment for sclerotic skin diseases.

PMID- 10063207
TI  - Clinical and immunological characterization of patients with systemic sclerosis
      overlapping primary biliary cirrhosis: a comparison with patients with systemic
      sclerosis alone.
AB  - Limited cutaneous systemic sclerosis (lSSc) or CREST syndrome is sometimes
      complicated by primary biliary cirrhosis (PBC). To characterize the clinical and
      immunological features of patients with SSc overlapping PBC (SSc-PBC), the
      clinical and laboratory data of 11 SSc-PBC were studied. Since all of the SSc-PBC
      were lSSc, the features of SSc-PBC were compared with those of 266 patients with
      lSSc alone. The sera from SSc-PBC showed a significantly higher positivity for
      anti-centromere antibody (ACA) (p < 0.0005) and higher reactivity to centromere
      protein-C. Although SSc-PBC more frequently exhibited calcinosis and
      telangiectasia (p < 0.05), there was no statistical difference in other features
      of CREST syndrome. There was no statistical difference in other scleroderma
      related features either. SSc-PBC were more frequently complicated with Sjogren
      syndrome (p < 0.05). The most prominent feature of SSc-PBC was a higher incidence
      of ACA than in lSSc alone.

PMID- 10063209
TI  - A Japanese case of dengue fever with lymphocytic vasculitis: diagnosis by
      polymerase chain reaction.
AB  - A 37-year-old Japanese male was admitted to Nagasaki University Hospital with
      abrupt onset of biphasic fever, general malaise and myalgia 9 days after coming
      back to Japan from Manila. He developed a rubella like erythematous rash 3 days
      after admission and purpuric eruption one week after admission. A biopsied
      specimen from the purpura revealed lymphocytic vasculitis with T cell dominance
      and without immunoglobulin or complement deposition around the blood vessels. RT
      PCR analysis on peripheral blood mononuclear cells using dengue virus specific
      primers confirmed the diagnosis of type 3 dengue fever. PCR analysis using virus
      specific primers is a rapid and valuable method for making a correct diagnosis of
      dengue fever.

PMID- 10063208
TI  - Differential expression of interferon gamma by mitogen-stimulated peripheral
      blood mononuclear cells among Kuwaiti psoriasis patients.
AB  - Most diseases exhibit characteristic profiles of cytokine expression, broadly
      subdivided into Th1, involving primarily cell-mediated responses, of which
      Interferon-gamma (INF-gamma), Interleukin-2 (IL-2) and Tumor Necrosis Factor
      alpha (TNF-alpha) are hallmarks, and Th2 processes, which often involve
      activation of the humoral arm of the immune system, resulting in elevated levels
      of IL-4, IL-5 and IL-10. Psoriasis, a disorder characterized by disfiguring skin
      lesions and elevated levels of activated CD4+ T helper lymphocytes in both
      peripheral blood and lesional tissue, exhibits a profile of cytokine expression
      that includes high levels of TNF-alpha and IFN-gamma, with low IL-5 and IL-10,
      indicating that immunologically, the pathogenesis of the disease is Th1. In this
      study, we report the results of an investigation of peripheral blood mononuclear
      cell cytokine expression among Kuwaiti psoriasis patients; we demonstrated two
      patterns of IFN-gamma production which may suggest differing pathogeneses. Whole,
      haparinized blood was donated by 17 patients with active psoriasis and 11 healthy
      control subject. Mononuclear cells were isolated by density centrifugation and
      cultured for 3 days in the presence or absence of a mitogen (PHA). Supernatants
      were assayed for IFN-gamma (a Th1 marker) and IL-10 (a Th2 marker) by enzyme
      linked immunoabsorption assay (ELISA). IFN-gamma expression by both PHA
      stimulated and unstimulated cultures from psoriatics significantly exceeded that
      of controls (p < 0.001), whereas no significant differences in IL-10 expression
      were noted between psoriatic and control subjects. Stimulation indices (cytokine
      concentration in PHA-stimulated/unstimulated cultures, SI) for psoriatic subjects
      were significantly higher than those of controls for IFN-gamma (p = 0.000), but
      not for IL-10. Ratios of SI (SI IFN-gamma/SL IL-10) for the psoriatic subjects
      also were significantly greater for the psoriatic subjects than for the controls
      (p = 0.003). However, within the psoriatic group, eight patients failed to show
      the expected elevation of IFN-gamma/IL-10 ratio as a result of high unstimulated
      levels of IFN-gamma production. The divergence of IFN-gamma expression within the
      psoriatic group may indicate two different modes of T lymphocyte activation
      contributing to the pathogenesis of psoriasis in this study.

PMID- 10063210
TI  - Juvenile chronic myelogenous leukemia, neurofibromatosis 1, and xanthoma.
AB  - The triple association of leukemia, xanthomatous skin lesions, and
      neurofibromatosis 1 (NF) was first described by Royer et al. in 1958. Most of the
      leukemias were of the juvenile chronic myelogenous type (JCML). We describe a 7
      year-old male child with xanthoma, neurofibromatosis 1, and juvenile chronic
      myelogenous leukemia. His mother also had NF1. We suggest that the presence of
      xanthomas and NF1 in a young child should raise awareness of the possible
      development of JCML, especially in patients with a family history of NF1.

PMID- 10063211
TI  - A reactive acrosyringeal proliferation in a patient with ectodermal dysplasia:
      eccrine syringofibroadenoma-like lesion.
AB  - A 33-year-old man with ectodermal dysplasia (ED) has suffered from keratotic,
      exudative, erythematous plaques on the genital area, thighs, and soles since age
      17. Verrucous soft nodules in a cobblestone arrangement developed on the
      erythematous plaque on his left thigh when he was 31 years old. Histologic
      examination of the verrucous nodules demonstrated that they were composed of
      anastomosing thin cords of uniform, cuboidal, epithelial cells and a
      fibrovascular stroma. The changes are indicative of eccrine syringofibroadenoma
      of Mascaro (ESFA), which has been reported as a neoplasm, a hamartoma, or a
      nevus. With etretinate treatment, the verrucous nodules completely disappeared
      within two months. Similar, but much flatter, verrucous lesions recurred and
      disappeared twice during the subsequent two years period. These verrucous lesions
      were likely induced by irritation from urine, stool, and/or mechanical friction.
      This case of ESFA in a patient with ED clearly showed a reactive process which
      was successfully managed with oral etretinate.

PMID- 10063212
TI  - A case of hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (HED) is a rare, hereditary, congenital disease
      that affects several ectodermal structures. It is characterised by the following:
      anhidrosis or hypohidrosis, dental abnormalities, hypotrichosis, and a
      characteristic facies. The face shows prominent frontal bosses, supraorbital
      ridges and depressed bridges. We experienced a case of hypohidrotic ectodermal
      dysplasia in a 43-year-old male who had four characteristic features. A skin
      biopsy from the palm showed a total absence of the eccrine glands. The diagnosis
      was made on the basis of clinical features and skin biopsy findings.

PMID- 10063213
TI  - Localized soft tissue angiomatosis with subsequent development of angiolymphoid
      hyperplasia with eosinophilia.
AB  - We report an unusual case of arteriovenous (AV) malformation (localized form of
      soft tissue angiomatosis): a reaction of angiolymphoid hyperplasia with
      eosinophilia (ALHE) developed over the lesion of this pre-existing AV
      malformation. To the best of our knowledge, there is no other report of ALHE in
      association with a pre-existing bona fide AV malformation. A 71-year-old woman
      consulted our clinic because a reddish, dome-shaped tumor on her preauricular
      region, present as a slightly elevated, skin-colored tumor since her childhood,
      had rapidly enlarged and become more elevated with color change during the
      preceding two months. The histological features of most of the lesion
      corresponded to those of soft tissue angiomatosis (localized form). The
      proliferative vessels underlying the soft tissue angiomatosis streamed out and
      welled into the dermis with an accompanying prominent inflammatory infiltrate
      composed of lymphoid cells and eosinophils: these histological features were
      characteristic of ALHE. The recent abrupt clinical changes in the tumor were
      considered to represent a reaction to the angiomatosis with development of ALHE.

PMID- 10063214
TI  - Hydroxyurea-related leg ulcers in a patient with chronic myelogenous leukemia: a
      case report and review of the literature.
AB  - The unusual appearance of extensive skin ulcerations has been reported in
      patients with chronic myelogenous leukemia (CML) undergoing continuous
      chemotherapy with hydroxyurea. It is thought that hydroxyurea, an antineoplastic
      agent with selective cytotoxicity for cells that divide most actively (such as
      those of the skin), causes these ulcerations through impairment of normal wound
      healing in areas of common trauma. The most common site of ulcers is the leg,
      where the ulcers are often extremely painful, with violaceous macules surrounding
      them, and are associated with extensive edema. On biopsy, histological vascular
      changes include leukocytoclastic vasculitis, perivascular lymphocytic
      infiltration, formation of thrombus, swelling of the endothelial cells, and
      thickening of the vascular walls. We report successful split-thickness skin
      grafting on hydroxyurea-related leg ulcers after preoperative discontinuation of
      hydroxyurea treatment in a patient with CML. The possible pathogenesis of
      hydroxyurea-related leg ulcers is discussed.

PMID- 10063215
TI  - A case of Unna-Thost disease accompanied by Epidermophyton floccosum infection.
AB  - We report herein a case of 61-year-old man with Unna-Thost disease
      (nonepidermolytic hereditary palmoplantar keratoderma) who had been suffering
      from refractory dermatophyte infection. Diffuse palmoplantar hyperkeratosis
      developed in his infancy. Coarse scaling, fissures, marked erythema, and nail
      deformities appeared in his early adult life. Microscopic examination revealed
      fungal elements in scales and nail particles. Cultures of those scales isolated
      Epidermophyton floccosum. Genealogical study demonstrated that his mother,
      sister, brother, daughter, and niece had had similar tylosis, and all of the
      affected individuals except his daughter had been proved to have E. floccosum or
      Trichophyton rubrum infection. Oral itraconazole (100mg/day) was highly effective
      in treating his dermatophytosis without any adverse effects. Scaling, fissures
      and underlying erythema disappeared within four months.

PMID- 10063216
TI  - Acanthotic type of eccrine poroma on the arm: report of a case.
AB  - A 72-year-old Japanese man with eccrine poroma on the arm is described. To the
      best of our knowledge, he is the fifth patient with this tumor on the arm
      reported from Japan. The histopathological type of the tumor of our patient was
      unique because it was acanthotic; those of the previous patients were all of the
      intradermal type.

PMID- 10063217
TI  - Localized hypopigmented mycosis fungoides in a 12-year-old caucasian boy.
AB  - Mycosis fungoides is uncommon during childhood. We describe a Caucasian child who
      presented a single hypopigmented lesion of mycosis fungoides.

PMID- 10063218
TI  - Subungual exostosis.

PMID- 10063219
TI  - Public relations: a shared responsibility.

PMID- 10063220
TI  - Addressing nicotine addiction in women. Role of the midwife.
AB  - Smoking is the leading preventable cause of cancer, cardiovascular disease, and
      other premature deaths among women in the United States. Tobacco use accounts for
      10% of perinatal mortality and is 100% preventable. Smoking is now more common
      among adolescent girls than among boys. Women's health care providers are in an
      excellent position to intervene in this growing epidemic. This article addresses
      the health consequences of smoking as well as the social, economic, and emotional
      toll of cigarette smoking on the woman and her family. The reasons women begin
      and continue smoking in spite of known risks are examined. The role of the
      midwife in treating nicotine addiction in women throughout the life span is
      examined. A theoretical model based on the woman's stage of change is presented
      as a framework for intervention. Behavioral and pharmacologic treatment
      recommendations are included. Opportunities for professional activities for
      community education and advocacy for a tobacco-free society are presented.

PMID- 10063221
TI  - Clostridium difficile-associated disease. Implications for midwifery practice.
AB  - Clostridium difficile-associated disease (CDAD), a gastrointestinal infection
      with a wide range of manifestations whose primary symptom is diarrhea, occurs
      when antibiotic medications, or rarely other drugs or conditions, disrupt the
      normal colonic microflora, making it susceptible to the growth of toxigenic C
      difficile. It is a significant nosocomial infection and an increased incidence
      has been noted in recent years. Although infrequently seen in midwifery
      practices, it does occur and may increase with the growing usage of intrapartal
      antibiotics. Midwives may evaluate and treat a client with an initial episode of
      mild to moderate CDAD; they also may manage collaboratively or refer for medical
      management those clients with recurrent or severe disease. This article reviews
      the epidemiology, pathogenesis, clinical presentation, prevention, and midwifery
      management of initial and recurrent CDAD. The limitation in the use of oral
      vancomycin due to the emergence of vancomycin-resistant enterococcus, resulting
      in metronidazole becoming the primary agent for treatment of CDAD, and the
      implications of this in the treatment of CDAD during pregnancy and lactation are
      addressed.

PMID- 10063222
TI  - The cost-effectiveness of home birth.
AB  - As health care costs increase and a growing number of women are without
      insurance, the one health service that every family needs deserves further
      attention. Even for the 40% of births covered by Medicaid, safe birthing
      alternatives that permit a reduction in the $150 billion Medicaid burden would
      allow the United States to devote more resources to other urgent priorities.
      Informed birthing decisions cannot be made without information on costs, success
      rates, and any necessary tradeoffs between the two. This article provides the
      relevant information for hospital, home, and birth center births. The average
      uncomplicated vaginal birth costs 68% less in a home than in a hospital, and
      births initiated in the home offer a lower combined rate of intrapartum and
      neonatal mortality and a lower incidence of cesarean delivery.

PMID- 10063223
TI  - Spontaneous pushing during birth. Relationship to perineal outcomes.
AB  - Vaginal birth is a recognized factor in perineal tissue damage and postpartum
      perineal pain. This study examined outcomes of 39 primiparous women who had
      spontaneous vaginal births. In a retrospective survey, women were asked to
      describe the type of pushing used to give birth and what the level of pain had
      been in the perineal (or vaginal) area during the first week postpartum. Labor
      and delivery chart data documented extent of episiotomy and/or laceration
      sustained. Eleven (28%) women reported using spontaneous bearing down efforts,
      and the remaining 28 (72%) were directed. Women who used spontaneous pushing were
      more likely to have intact perineums postpartum and less likely to have
      episiotomies, and second or third degree lacerations (chi 2 [3, N = 39] = 8.1, P
      = .043). Other variables, such as maternal age, infant birth weight, length of
      second stage, provider type, and use of epidural, did not demonstrate a
      significant difference in perineal outcome. Further analysis showed a significant
      relationship between the extent of perineal disruption and pain (F [3,30] = 5.08,
      P = .005).

PMID- 10063224
TI  - The effect of uterine rupture on fetal heart rate patterns.
AB  - The high success rate of vaginal birth after cesarean section (VBAC) and its low
      association with complications has led to VBACs being attempted at all types of
      facilities, including birth centers. It must be kept in mind that unpredictable
      uterine rupture can occur and that uterine rupture necessitates emergency
      intervention. The only reported predictable feature of fetal heart rate patterns
      in response to uterine rupture is the sudden onset of fetal bradycardia. Fetal
      patterns are presented to illustrate this finding.

PMID- 10063225
TI  - Public education: promoting the midwifery model of care in partnership with the
      Maternity Center Association.
AB  - Most people who are ignorant or misinformed about midwifery are also misinformed
      about birth, the needs of pregnant women, and problems related to the care
      provided to most pregnant women in this country. An understanding of these issues
      is the conceptual substrate that makes it possible to understand and value
      midwifery. Although midwives need to educate people about midwives and midwifery,
      it is also necessary for them to educate people about the nature of childbirth,
      the needs of pregnant women in general, and appropriate (and inappropriate)
      maternity care. Midwives are experts in these subjects, but they have to go
      beyond talking about midwifery--beyond talking about themselves. To maximize
      their effectiveness, midwives should work in partnership with individuals and
      organizations that support the midwifery model of care--regardless of the
      professional background of the person who practices this model. Midwives can
      advance public education by collaborating with organizations, such as the
      Maternity Center Association (MCA), which supports family-centered maternity
      care, based on the midwifery model. MCA's current public education activities are
      described and two new MCA brochures are presented. Information that supports
      midwifery care may be particularly effective when it is presented by an
      organization with broader objectives.

PMID- 10063226
TI  - Creating off-campus/distance learning courses for midwifery education. A brief
      introduction.
AB  - Midwifery education is undergoing a curriculum revolution that is reflective of
      current trends in other fields. Distance learning programs have developed in
      response to these changes. This article provides an overview of a student
      centered transactional educational model, discusses the role of faculty as
      midwife-teachers, and reviews the factors influencing technology decisions for
      distance education. Curricular structure is discussed and ideas for learning
      activities are presented to assist faculty considering the development of off
      campus, distance learning courses.

PMID- 10063227
TI  - Postpartum depression. The lived experiences of Middle Eastern migrant women in
      Australia.
AB  - The aim of this study was to explore the lived experiences of postpartum
      depression among the Middle Eastern women living in Sydney, Australia. A
      phenomenologic research design was used to conduct in-depth, unstructured
      interviews with a purposive sample of 45 mothers who had experienced postpartum
      depression. The interviews were conducted in the mothers' homes. Transcriptions
      of these interviews were analyzed using Colaizzi's (1978) phenomenologic method.
      Five themes emerged that illustrated the Middle Eastern woman's experiences of
      postpartum depression: 1) loneliness due to feelings of isolation and lack of
      social support, 2) helplessness due to inability to cope with the overwhelming
      task of fulfilling her traditional role as mother and wife, 3) fear of failure
      and being labeled a "bad mother" by in-laws, 4) insufficient knowledge about
      postpartum depression and available support services, and 5) coming to terms with
      postpartum depression by undertaking diversional activities and learning new
      skills. The exhaustive description of postpartum depression as experienced by the
      women that emerged from this phenomenologic study will help midwives and other
      health care professionals to be more sensitive to and understanding of women from
      different cultural backgrounds so that appropriate interventions can be designed
      that meet their specific needs and beliefs.

PMID- 10063228
TI  - The midwifery solution to contemporary problems in American obstetrics.
AB  - This article focuses on midwifery as one solution to many of the problems that
      confront contemporary American obstetrics. Documented evidence with historic
      perspective that supports the view that midwifery should become the mainstream in
      maternity care in the United States, not an alternative, is presented. The role
      differences and conflicts that tend to arise between doctors and midwives are
      discussed and collaboration between the two professional groups is suggested as
      yet another solution to the problem.

PMID- 10063229
TI  - Outcomes of intended home births in nurse-midwifery practice: a prospective
      descriptive study.

PMID- 10063230
TI  - Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection.

PMID- 10063231
TI  - The effects of self-administering emergency contraception.

PMID- 10063232
TI  - An immunohistochemical study of cadherin 5 (VE-cadherin) in vascular endothelial
      cells in placentas with gestosis.
AB  - OBJECTIVE: To evaluate vascular endothelial-cell functioning in placentas with
      gestosis, using the monoclonal antibody to cadherin 5. METHODS: The extra
      cellular moiety of cadherin 5 was transfected into L-cells to enable us to
      examine their cell-adhesion activity. The expression of cadherin 5 was evaluated
      in human umbilical-vein endothelial cells and in placentas with gestosis by
      immunostaining using the anti-cadherin 5 antibody. A microspectrophotometric
      study also was conducted of the placentas with gestosis. RESULTS: We determined
      the total base sequence for cadherin 5 and found that it is homologous with a
      known cadherin but is a new, unique clone. Cadherin 5 has cell-adhesion activity
      and is expressed in endothelial cells at the cell-adhesion surface. The
      expression of cadherin 5 in endothelial cells took place in the placentas with
      gestosis, but to a lesser extent than in normal placental endothelial cells.
      CONCLUSIONS: The reduced expression of cadherin 5 in placentas with gestosis
      suggests that endothelial cell functioning is impaired in placentas with
      gestosis. Cadherin 5 in endothelial cells might influence placental functions and
      fetal development.

PMID- 10063233
TI  - Detection of numerical chromosome abnormalities in human spermatozoa by three
      color fluorescence in situ hybridization.
AB  - Three-color fluorescence in situ hybridization (FISH) was used to detect
      numerical X, Y, and 17 chromosomal aberrations in human sperm nuclei.
      Digoxigeninlabeled alpha satellite chromosome X-specific probe DXZ1, biotin
      labeled classical satellite chromosome Y-specific probe DYZ1, and biotin plus
      digoxigenin-labeled alpha satellite chromosome 17-specific probe D17Z1 were
      simultaneously hybridized to sperm preparations from donors with normal semen
      (group A) and abnormal semen (group B) characteristics. The proportions of
      haploid X, Y, 17 and disomy, diploidy of them before and after swim-up were
      determined. At least 3,000 sperm were analyzed for each sample. Overall, up to
      98% of sperm were labeled with the probes, and all statistical analyses were
      performed using chi 2 tests. A significant difference was observed between group
      A and group B in frequency of sex chromosome disomy (p < 0.05). In group B, there
      were significant differences in frequencies of sex chromosomes disomy (p < 0.05)
      and diploidy (p < 0.01) before to after swim-up. There was no significant
      difference in frequency of disomy 17 between the 2 groups. In group A and B, the
      ratios of X- to Y-bearing sperm were 1:1 (neat semen), but in both groups there
      was a significant increase in Y-bearing sperm after swim-up. The results of this
      study demonstrated that abnormal semen has sex chromosome disomy more frequently
      than does normal semen and that portion of sex chromosome disomic and diploid
      sperm is removed by swim-up, especially for abnormal semen. These findings
      suggest that we should be careful in using abnormal semen for IVF, especially for
      ICSI, and should perform swim-up if possible.

PMID- 10063234
TI  - Fertility outcome after reversal of sterilization.
AB  - OBJECTIVE: The study was designed to evaluate the fertility outcome in
      sterilization reversals and a variety of factors that have been suggested to
      influence the successful outcome of sterilization reversal procedures. METHOD: It
      is a retrospective study involving all sterilization reversals performed between
      January 1991 and December 1995 in our hospital. A total of 58 cases were treated.
      Tubal anastomosis was performed according to rules of microsurgery. The loupe
      microsurgical technique with 4 x magnification comprising two main phases,
      preparation of healthy tubal segments and anastomosis carried out in two layers.
      RESULTS: It was possible to study subsequent fertility of 50 patients in all, as
      8 patients were lost to follow-up (13.76%). The overall conception rate was 68%
      (34 cases), out of which intrauterine pregnancy rate was 62% (31 cases), ectopic
      pregnancy rate was 6% and the abortion rate was 6%. Fifty percent of patients
      conceived within first 12 months of reversal of sterilization. The isthmic
      isthmic type of anastomosis has maximum incidence of pregnancies (88.88%).
      CONCLUSION: Laparoscopic (Falope ring) sterilization should be preferred in women
      who are willing for interval sterilization and it should be done at isthmic
      segment of the tube, whereas the Pomeroy's method is to be reserved for
      occasional postpartum procedure. Reversal of sterilization should be done with
      strict adherence to principles of microsurgery.

PMID- 10063235
TI  - Single agent versus combination chemotherapy in recurrent cervical cancer.
AB  - OBJECTIVE: Cisplatin and ifosfamide are two most active agents in patients with
      recurrent and metastatic cervical cancer. Combination of bleomycin, ifosfamide
      and cisplatinum (BIP) was compared with cisplatinum alone. PATIENTS AND METHODS:
      One hundred and six patients with recurrent/persistent and metastatic cervical
      cancer received either a combination of bleomycin, ifosfamide and cisplatinum,
      (Group A, n = 50) or cisplatinum alone (Group B, n = 56) every 3 weeks for up to
      6 courses. Ninety-seven patients were evaluable and were analysed for response
      and survival. RESULTS: Patients receiving BIP (Group A) had a higher response
      rate (complete and partial responses), 52.2% vs 29.4%, p < 0.01 with overall
      median survival, 8 months (1 to 92+ months) vs 6 months (1 to 40+ months), p =
      0.18. Chemotherapy responders had a significantly higher survival in both groups
      compared to the non-responders (Group A: 17 vs 6 months, p < 0.001, Group B: 20.5
      months vs 5 months, p < 0.001). Patients in good performance status (ECOG, 0-2)
      had a significantly higher response rate to chemotherapy (Group A: 70.3% vs
      26.3%, p < 0.01, Group B: 38.2% vs 11.7%, p < 0.05). In Group A, patients with
      extrapelvic disease responded better compared to pelvic disease (83.3% vs 34.5%,
      p < 0.01). Chemotherapy side effects were mainly nausea/vomiting, alopecia,
      myelosuppression, reversible encephalopathy (in Group A), and impaired renal
      functions. Chemotherapy toxicity was higher for patients receiving BIP, 2
      patients died of BIP toxicity. Currently, in 'Group A' 8 patients are alive, 7
      disease-free and one with disease at a median interval of 51 months after
      chemotherapy treatment. While in Group B, 3 patients are alive, 2 disease-free
      and one with disease. CONCLUSIONS: Bleomycin, ifosfamide and cisplatin improved
      the response rate in recurrent and metastatic cervical cancer compared with
      cisplatinum alone. However, the toxicity was moderate and survival was not
      significantly improved. These results need to be confirmed in a phase III,
      randomized study in larger number of patients.

PMID- 10063236
TI  - Evaluation of insulin-like growth factor binding protein-1 as a diagnostic tool
      for rupture of the membranes.
AB  - OBJECTIVE: To evaluate the diagnostic value of insulin-like growth factor binding
      protein-1 (IGFBP-1) as an indicator of ruptured fetal membranes. METHODS: IGFBP-1
      concentrations were measured on 42 paired cervicovaginal samples before and after
      membrane rupture, using an immunoenzymatic assay. A PROM test [dipstick detecting
      IGFBP-1 with a cutoff value of 25 micrograms/l (A)], a BTB test (B), a ROM-Check
      (C), and a fern test (D) were compared in diagnosing ruptures of the membranes in
      48 patients. RESULTS: The optimal cutoff concentration was between 20.1
      micrograms/l and 148.4 micrograms/l by receiver operating characteristic curve
      analysis. The PROM test had the highest sensitivity (94.7%) and highest
      specificity (93.3%) (sensitivity of A-D, B-D, C-D and specificity of A-B: p <
      0.05 by chi 2-test). Unlike the other tests, the PROM test is unaffected by
      contamination, cervical dilatation, or uterine contraction. CONCLUSIONS: The
      measurement of IGFBP-1 in vaginal fluids is useful for the diagnosis of ruptured
      fetal membranes.

PMID- 10063237
TI  - Current status in intrauterine fetal stem cell therapy.
AB  - In utero fetal stem cell transplantation, a today experimental treatment option,
      represents a new therapeutic strategy with broad implications for diseases
      related to the hematopoietic system. The object of the present paper is to give a
      review of the published literature on fetal stem cell therapy with special
      reference to immunological and strategical considerations. Furthermore, ethical
      considerations on account of the use of fetal cells are pointed out and a
      prospective view concerning experimental and clinical future perspectives is
      presented.

PMID- 10063238
TI  - The necessity for a progressing dialog between basic science and clinical
      research in obstetrics and gynecology.
AB  - Scientific breakthroughs and basic research are frequently published in
      prestigious journals and praised for their impact. However, progress in clinical
      medicine is tedious and slow. There is still a distinct and even widening gap
      between basic science and clinical application. The dialog between basic science
      and clinical research has therefore to be intensified and a new culture of
      cooperation between basic and physician-scientists will become necessary to
      accelerate the transfer of new drugs into clinical practice.

PMID- 10063239
TI  - Conservative surgery for microinvasive carcinoma of the cervix.
AB  - OBJECTIVE: To evaluate the prognosis of patients with stage IA1 and IA2
      microcarcinoma of the cervix according to the 1994 FIGO classification. METHODS:
      The histologic specimens of 494 patients who underwent conization for
      microcarcinoma of the cervix between 1958 and 1992 were reviewed and classified
      according to the 1994 FIGO system. RESULTS: After a mean follow-up of 14 years
      (range, 1-35) 2 patients with stage IA1 tumors and 2 patients with stage IA2
      tumors died of disease. Patients with early stromal invasion only accounted for
      70% of patients with stage IA1 lesions. If these patients are excluded from stage
      IAI, the mortality rates for stage IA1 and IA2 did not differ significantly.
      Surgical radicality declined markedly during the study period. CONCLUSION:
      Neither the 1985 nor the 1994 FIGO classification of microcarcinoma can be used
      as a guide to therapy. Conization only suffices for patients with early stromal
      invasion or a depth of invasion of 1-3 mm without lymph vascular space
      involvement. Additional pelvic lymphadenectomy can be considered for patients
      with stage IA1 lesions with lymph vascular space involvement. Removal of the
      tumor and pelvic lymphadenectomy is indicated for all patients with stage IA2
      lesions, regardless of lymph vascular space involvement. Radical vaginal or
      radical abdominal hysterectomy represent overtreatment for patients with
      microcarcinomas because parametrial involvement in these patients has not been
      demonstrated.

PMID- 10063240
TI  - Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical
      study of 54 cases.
AB  - OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras
      expression and ploidy in borderline tumors of the ovary by assessing their
      frequency, and relationship to histologic type, tumor recurrence and survival.
      METHODS: Fifty-four patients with borderline tumors were followed 3-140 months
      (median: 38 months). Paraffin-embedded sections were stained using monoclonal
      antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and
      ras. The immunohistochemical findings were correlated to histologic subtype,
      tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24%
      (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive,
      Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl
      2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases,
      respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER
      2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with
      ovarian borderline tumors. Further studies to evaluate their prognostic value are
      warranted.

PMID- 10063241
TI  - Operative results after primary and secondary debulking-operations in advanced
      ovarian cancer (AOC).
AB  - OBJECTIVE: To assess the role of primary and secondary radical surgery in
      advanced ovarian cancer (AOC). DESIGN: Retrospective study. METHODS: One hundred
      and fifty-one patients with AOC (FIGO III/IV) underwent altogether 191 extended
      multivisceral operations between 1/1992 and 2/1998. The statistic analysis
      compared the primary with the secondary operations. RESULTS: One hundred and
      seventeen patients had a primary, 63 patients had a secondary and 18 patients a
      tertiary operation because of relapse of ovarian cancer. Surgical procedures
      entailed respectively: small-bowel-resection (21%/48%), colon resection
      (39%/58%), colostomy (9%/11%), ileostomy (2%/4%), ileum-pouch (0%/6), splenectomy
      (3%/3%), pelvic floor-covering (4%/6%), peritoneal removal (24%/21%), infrared
      contact coagulation (4%/6%). Seventy-five percent of the patients had no
      complications: relaparotomy (3%/3%), fistula (3%/6%), short-bowel-syndrome
      (5%/11%), postoperatively mortality (2%/6%). Postoperative tumor-free were
      26%/22%, 57% and 65% had residual disease < or = 2 cm, 16%/13% > 2 cm.
      CONCLUSIONS: Radical multivisceral surgery is feasible, safe and efficient in
      primary as well in secondary situation of advanced ovarian cancer.

PMID- 10063242
TI  - Intrauterine fetal death during pregnancy: limitations of fetal surveillance.
AB  - OBJECTIVE: Perinatal statistics in Germany have shown that fetal death during
      pregnancy remained unchanged during the past 12 years. The question arises
      whether the quality of prenatal care can be improved and contributing factors to
      ante partum mortality (APM) reduced. METHODS: The perinatal data base from Hesse
      was evaluated for 1990-1995. It comprises 347,463 deliveries in a population
      based survey from the state of Hesse/Germany. Antepartum death occurred in 1,133
      cases (0.33%). Pregnancy care was evaluated in a longitudinal investigation
      analysed from 1982 to 1995. RESULTS: Fetal surveillance showed during the past
      years a steady improvement demonstrated by the number antenatal visits of more
      than 10: it rose from 54 to 75%, by the CTG recordings ante partum: it increased
      from 55 to 90% and ultrasound examinations more than 5: it rose from 12 to 26%.
      Despite the increase of ante partum care fetal death during pregnancy remained
      constant since 1985 at 0.5 to 0.6%. Malformations contribute to APM in 8.3%. In
      44.4% various risk factors could be identified, whereas in 47.4% no causes could
      be shown. Special risk factors are hydramnios, diabetes, placenta praevia,
      multiple pregnancy, IUGR and others. Fetal death occurs preferentially during the
      last weeks of pregnancy with a maximum at 40 weeks of gestation. Social burden
      and insufficient prenatal care are contributing factors to APM. CONCLUSION: APM
      can still be improved by using simple clinical estimates and by defined
      application of surveillance tools at present available.

PMID- 10063243
TI  - Child drawing: hospital--an instrument designed to measure the emotional status
      of hospitalized school-aged children.
AB  - Hospitalization has long been accepted as a stressful experience for children,
      but the degree of anxiety experienced by any child is unknown. Physiological
      status is routinely measured, but the same is not true for emotional status. "The
      Child Drawing: Hospital" was developed as a means of measuring the emotional
      status of the hospitalized school-aged child. This report presents the validity
      and reliability of the "Child Drawing: Hospital" as a measure of anxiety for
      hospitalized children.

PMID- 10063244
TI  - Child drawing: hospital manual.

PMID- 10063245
TI  - Preverbal, Early Verbal Pediatric Pain Scale (PEPPS): development and early
      psychometric testing.
AB  - The Pre-Verbal, Early Verbal Pediatric Pain Scale (PEPPS) is conceptualized to
      measure the established pain response in toddlers, a pediatric group void of pain
      assessment scales. It consists of seven categories, each with weighted
      indicators. Scores can range from 0 to 26. Using a blinded, cross-sectional
      design, 40 children, aged 12 to 24 months, were videotaped throughout their
      postoperative stay in the postanesthesia care unit. Vignettes were randomly
      selected and viewed by four experienced pediatric nurses. Results indicated that
      the PEPPS was easy to use and demonstrated acceptable inter-rater and intrarater
      reliability. Early evidence of construct validity was established by
      statistically significant differences in premedication and postmedication pain
      scores.

PMID- 10063246
TI  - Thematic instrument for measuring death anxiety in children (TIMDAC).
AB  - Few instruments measure death anxiety in children, especially, children of color.
      This article describes the development and psychometric properties of the
      projective instrument, the Thematic Instrument for Measuring Death Anxiety in
      Children (TIMDAC), a culturally sensitive tool that was developed to compare
      levels of death anxiety in children diagnosed with acquired immune deficiency
      syndrome (AIDS) and health peers. Many of the children with AIDS are African
      Americans and Latinos.

PMID- 10063247
TI  - A Multidimensional Sense of Humor Scale for school-aged children: issues of
      reliability and validity.
AB  - The Multidimensional Sense of Humor Scale (MSHS) was revised to assess sense of
      humor in school-aged children. One hundred sixteen children completed the
      modified MSHS. Chronbach alpha coefficients were .88 for the total scale and
      ranged from .78 to .85 for the subscales. Item to total MSHS score correlations
      ranged from .35 to .71. Concurrent validity was supported with a positive
      correlation between total MSHS score and children's rating of their degree of
      sense of humor (r = .42, P < .001). Although further testing is suggested, the
      modified MSHS can be used in clinical and research settings to assess a child's
      sense of humor and determine the appropriateness and effectiveness of using humor
      with children as they cope with childhood stressors.

PMID- 10063248
TI  - The nurse parent support tool.
AB  - This report describes the development of an instrument, the Nurse-Parent Support
      Tool (NPST) designed to measure parents' perception of nursing support during
      their child's hospitalization. The NPST was based on the Nurse Parent Support
      Model developed from House's conceptualizations of four domains of support. Thus,
      the 21-item NPST assesses four dimensions of support: (1) supportive
      communication and provision of information related to the child's illness,
      treatments, care, and related issues; (2) parental esteem support focused on
      respecting, enhancing, and supporting the parental role; (3) emotional support to
      help the parents cope with their own emotional responses and needs related to the
      child's illness; and (4) caregiving support involving the quality of care
      provided to the child. Strong support for the content validity of the NPST
      derives from the steps used in constructing the instrument. This includes use of
      a conceptual framework, generating items from the literature, using data from
      interviews with parents of hospitalized children, and pilot testing with parents
      and experts. Factor analysis provides support for the underlying construct and
      significant correlations with another instrument measuring a similar construct
      provides support for the concurrent validity. The internal consistency
      reliability is very high. The NPST holds promise for use in nursing research and
      quality improvement programs in pediatric and neonatal in-patient settings.

PMID- 10063249
TI  - American and Korean adolescents' physical and mental health self-efficacy.
AB  - Self-efficacy beliefs are thought to have causal influence on behavior, helping
      to explain what tasks people approach, persevere at, or abandon. Few cross
      cultural studies of adolescents' self-efficacy beliefs have been conducted or
      reported. We compared physical and mental health self-efficacy beliefs of Korean
      and American high school students. A Korean translation of the English language
      School Health Efficacy Questionnaire (SHEQ) was used in data collection. The
      translated version of the SHEQ showed psychometric estimates similar to the
      original English language version. Sizable age and culturally related differences
      were found on both physical and emotional health self-efficacy perceptions
      between the two groups of adolescents.

PMID- 10063250
TI  - An adolescent and young adult condom self-efficacy scale.
AB  - The purpose of this study was to initially test the psychometric properties of an
      adolescent and young adult condom self-efficacy scale. The sample consisted of
      209 participants (13 to 26 years old) who voluntarily completed a 19-item scale.
      The items were developed based on a review of the literature and a review by
      experts in adolescents' and young adults' condom use. Item analysis was conducted
      and five items were deleted. Principal axis factor analysis with varimax rotation
      yielded three factors: communication abilities related to condom use, consistent
      condom use abilities, and correct condom use abilities. The three factors
      accounted for 42% of the variance. The alpha coefficient was .85 for the total
      scale. The scale could be used to assess perceived condom self-efficacy and to
      evaluate effectiveness of strategies to increase perceived condom self-efficacy
      among adolescents and young adults.

PMID- 10063251
TI  - Federally supported programs for children and their families.

PMID- 10063262
TI  - Typical household vacuum cleaners: the collection efficiency and emissions
      characteristics for fine particles.
AB  - The issue of fine particle (PM2.5) exposures and their potential health effects
      is a focus of scientific research because of the recently promulgated National
      Ambient Air Quality Standard for PM2.5. Before final implementation, the health
      and exposure basis for the standard will be reviewed by the U.S. Environmental
      Protection Agency within the next five years. As part of this process, it is
      necessary to understand total particle exposure issues and to determine the
      relative importance of the origin of PM2.5 exposure in various micro
      environments. The results presented in this study examine emissions of fine
      particles from a previously uncharacterized indoor source: the residential vacuum
      cleaner. Eleven standard vacuum cleaners were tested for the emission rate of
      fine particles by their individual motors and for their efficiency in collecting
      laboratory-generated fine particles. An aerosol generator was used to introduce
      fine potassium chloride (KCl) particles into the vacuum cleaner inlet for the
      collection efficiency tests. Measurements of the motor emissions, which include
      carbon, and the KCl aerosol were made using a continuous HIAC/Royco 5130 A light
      scattering particle detector. All tests were conducted in a metal chamber
      specifically designed to completely contain the vacuum cleaner and operate it in
      a stationary position. For the tested vacuum cleaners, fine particle motor
      emissions ranged from 9.6 x 10(4) to 3.34 x 10(8) particles/min, which were
      estimated to be 0.028 to 176 micrograms/min for mass emissions, respectively. The
      vast majority of particles released were in the range of 0.3-0.5 micron in
      diameter. The lowest particle emission rate was obtained for a vacuum cleaner
      that had a high efficiency (HEPA) filter placed after the vacuum cleaner bag and
      the motor within a sealed exhaust system. This vacuum cleaner removed the KCl
      particles that escaped the vacuum cleaner bag and the particles emitted by the
      motor. Results obtained for the KCl collection efficiency tests show > 99% of the
      fine particles were captured by the two vacuum cleaners that used a HEPA filter.
      A series of tests conducted on two vacuum cleaners found that the motors also
      emitted ultra-fine particles above 0.01 micron in diameter at rates of greater
      than 10(8) ultra-fine particles/CF of air. The model that had the best collection
      efficiency for fine particles also reduced the ultra-fine particle emissions by a
      factor of 1 x 10(3).

PMID- 10063267
TI  - Opportunistic hepatic infections in AIDS patients with fever of unknown origin.
AB  - The clinical features and histopathologic manifestations of hepatic opportunistic
      infections in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan
      remain unexplored. We report 28 AIDS patients (25 men, 3 women; mean age, 34
      years) with fever of unknown origin who underwent 31 liver biopsies from December
      1995 to May 1997. In most cases, the biochemical tests showed moderate to
      markedly elevated alkaline phosphatase concentrations, but normal or mildly
      elevated aminotransferase concentrations. The most common histopathologic finding
      was macrosteatosis, which was noted in 15 of the 28 patients. Another important
      histopathologic finding indicating the etiology of hepatic opportunistic
      infection was granuloma, which was found in 11 patients. Histochemical stain and
      culture of liver specimens yielded Mycobacterium avium complex (MAC) in eight
      patients, Mycobacterium tuberculosis in two patients, Histoplasma capsulatum in
      one patient, and cytomegalovirus in one patient with concomitant MAC infection.
      Therefore, a definitive diagnosis in AIDS patients with fever of unknown origin
      was made in 11 of the 28 cases with the assistance of liver biopsy. During follow
      up, late extrahepatic involvement by the same infectious agents was found in six
      patients. Thus, hepatic manifestations could be a harbinger of disseminated
      opportunistic infections in AIDS patients.

PMID- 10063268
TI  - Human leukocyte antigen polymorphisms in the Taiwanese population.
AB  - Polymorphisms of human leukocyte antigens (HLA) are important in transplantation
      medicine, anthropologic studies, and paternity testing. We investigated the
      polymorphisms of HLA classes I and II in the Taiwanese population by means of
      serologic typing and polymerase chain reaction (PCR) analysis with sequence
      specific primers. We calculated the HLA-A, -B, and -C gene frequencies in 673
      Taiwanese subjects and the HLA-DRB1, and HLA-DQB1 gene frequencies in 204
      subjects with available DNA samples. Haplotype frequencies and linkage
      disequilibrium were analyzed on the basis of these data. The common HLA class I
      antigens were A11 (gene frequency, 34.9%), A2 (29.3%), A24 (15.8%), and A33
      (9.8%); B60 (21.9%), B46 (13.1%), B58 (9.7%), and B13 (8.5%); and Cw1 (18.8%),
      Cw7 (15.3%), and Cw10 (10.7%). The common HLA-DRB1 and HLA-DQB1 alleles were
      DRB1*12 (15.2%), DRB1*09 (15.2%), DRB1*08 (12.0%), and DRB1*04 (12.0%); and
      DQB1*0301 (23.5%), DQB1*0303 (15.2%), DQB1*0601 (14.5%), and DQB1*02 (10.8%). The
      common two-locus haplotypes were A2-B46 (frequency, 9. 7%), A11-B60 (9.6%), and
      A33-B58 (6.8%); DRB1*09-DQB1*0303 (14.9%), DRB1*12-DQB1*0301 (14.2%), and DRB1*08
      DQB1*0601 (10.7%). This study is the first to report the gene frequencies of HLA
      DQB1 alleles and the common HLA-DR-DQ haplotypes among Taiwanese. Comparison of
      our results with those from two other Chinese populations in mainland China
      reveals that Taiwanese are more closely related to southern Han than to northern
      Han Chinese.

PMID- 10063269
TI  - Cognition and utilization of Papanicolaou testing after the implementation of
      National Health Insurance in rural Taiwan.
AB  - Previous reports have indicated that knowledge and utilization of Papanicolaou
      (Pap) testing in Taiwan are low, especially among residents of rural areas.
      However, those studies were conducted before the implementation of National
      Health Insurance (NHI), which now covers Pap testing. To assess the cognition and
      utilization of Pap testing after the implementation of NHI in 1995, 708 women
      aged 40 years or more were interviewed by the Yang-Ming Crusade in July 1997. Of
      these women, 276 (39%) had heard of the Pap test, 226 (32%) had had the test, and
      156 (22%) had had the test in the last 3 years (1995-1997). Of those who had
      never had the Pap test before 1995, 17% underwent it for the first time after the
      implementation of NHI. In contrast to an earlier comparable study, the present
      study shows a significant increase in both the cognition and utilization rates of
      Pap testing (from 27% to 39%, and 18% to 32%, respectively) among women in rural
      areas after the test was covered by NHI. However, both knowledge and use of the
      test among older and lower-educated women are still low.

PMID- 10063270
TI  - T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies.
AB  - The activation status of T lymphocytes and the presence of various cytokines in
      ascitic fluid were examined to test peritoneal immunity in women with ovarian
      malignancies. Peripheral blood and peritoneal fluid were collected from 12
      patients with primary ovarian cancer with ascites and 27 normal control subjects
      during laparoscopic examination. Lymphocyte subpopulations and the expression of
      activation markers on T lymphocytes were analyzed by dual-color flow cytometry.
      The concentrations of various cytokines and soluble interleukin (IL)-2 receptor
      alpha were measured. CD8 T lymphocytes were the main component of peritoneal
      lymphocytes. CD69 and HLA-DR, but not CD25, were highly expressed on peritoneal T
      lymphocytes compared to those in peripheral blood. In ascitic fluid of ovarian
      malignancies, CD4 T lymphocyte concentrations were further decreased, resulting
      in a decreased CD4/CD8 ratio. Decreased expression of CD69 and CD25 was also
      noted on T lymphocytes from ascites compared with T lymphocytes in normal
      peritoneal fluid. IL-1b, tumor necrosis factor-alpha, IL-6, and soluble IL-2
      receptor-alpha concentrations were increased significantly in the ascitic fluid
      of women with ovarian cancer. The decrease in activation markers on T lymphocytes
      is suggestive of an immunosuppressive state, despite the presence of abundant
      stimulatory cytokines. The immunosuppression may be multifactorial, attributed,
      in part, to the increased concentrations of soluble IL-2 receptor-alpha and other
      inhibitors.

PMID- 10063271
TI  - Expression and mutation analysis of the p53 gene in astrocytoma.
AB  - The role of p53 gene mutations in the formation or progression of human
      astrocytic tumors is controversial. We studied the distribution pattern of p53
      immunoreactivity and analyzed p53 gene mutations to define the significance of
      p53 gene mutations in astrocytoma tumorigenesis or malignant progression. Twenty
      three astrocytic tumors were evaluated with immunohistochemistry, single-strand
      conformation polymorphism (SSCP) analysis, and sequence analysis. We also
      searched MEDLINE to collect data on p53 gene mutation frequencies in astrocytic
      tumors in order to evaluate the association of p53 mutations and tumor grade.
      Strong immunoreactivity with a diffuse clustering pattern was found in three of
      five glioblastomas and seven of 12 anaplastic astrocytomas. Three of four low
      grade astrocytomas were immunonegative. The p53 immunopositive cells in the only
      positively staining low-grade astrocytoma in our study appeared sparsely
      scattered. The results of immunostaining suggested that clonal expansion was
      associated with astrocytoma progression. Mutations of the p53 gene were detected
      in four of the 23 astrocytomas (one glioblastoma and three anaplastic
      astrocytomas). In the genetic data analysis, 76 of 367 astrocytomas had p53 gene
      mutations. A significantly greater p53 gene mutation frequency was found in
      anaplastic astrocytomas or glioblastomas than in the low-grade astrocytomas. The
      results of these immunohistochemical and genetic studies support the view that
      p53 gene mutation is associated with the malignant progression from low-grade to
      high-grade astrocytomas rather than with tumor initiation or promotion.

PMID- 10063272
TI  - Modulatory effect of blood cells on hypoxic vasoconstriction response and nitric
      oxide release in rat lungs.
AB  - In this study, we investigated the modulatory effects of different types of blood
      cells on hypoxic pulmonary vasoconstrictive (HPV) response and nitric oxide (NO)
      release in isolated rat lungs. The lungs were perfused at a constant flow with
      physiologic saline solution (PSS). The changes in pulmonary arterial pressure
      (PAP) and NO release were observed. Two hypoxic challenges with a 5% CO2-95% N2
      gas mixture were carried out in each experiment. Hypoxia induced pulmonary
      vasoconstriction, as reflected by an increase in PAP (0.88 +/- 0.22 cmH2O). At
      the same time, NO (342.9 +/- 78.3 mv) release from the lungs was also increased.
      Addition of white blood cells (WBCs, 0.70 to 0.88 x 10(5)/mL), platelets (1.48 to
      1.96 x 10(5)/mL), or red blood cells (RBCs, 4.6 to 6.6 x 10(5)/mL) into the
      perfusate produced different effects on PAP and NO changes. WBCs decreased the
      pulmonary vasoconstriction response and this was accompanied by an increase in NO
      release. Platelets had no significant effects on either PAP or NO. RBCs
      significantly potentiated the PAP increase and attenuated the NO release. The
      results indicate that NO release during hypoxia tends to offset pulmonary
      vasoconstriction and that NO release and HPV response are modulated by different
      cell elements.

PMID- 10063273
TI  - Antimicrobial susceptibilities of clinical isolates of vancomycin-resistant
      enterococci in Taiwan.
AB  - To understand the antimicrobial resistance patterns of vancomycin-resistant
      enterococci in Taiwan, we tested the in vitro activities of 10 antimicrobial
      agents against 71 clinical isolates (39 of Enterococcus faecalis and 32 of
      Enterococcus faecium) by means of the agar dilution method. Resistance was
      determined on the basis of the minimum inhibitory concentration (MIC) of each
      antimicrobial agent--MIC50 and MIC90 (minimum concentrations required to inhibit
      growth of 50% and 90% of isolates, respectively) were determined. No beta
      lactamase producers were identified with the cefinase test. All E. faecalis
      isolates were susceptible to penicillin and ampicillin, and 97% of these isolates
      were resistant to teicoplanin (vanA phenotype). Of the E. faecium isolates, 75%
      were susceptible to teicoplanin (vanB phenotype) and most were resistant to
      penicillin (94%) and ampicillin (94%). Quinupristin/dalfopristin was markedly
      less active against E. faecalis than E. faecium isolates (MIC50, 64 vs 2
      micrograms/mL; MIC90, 128 vs 8 micrograms/mL; susceptibility rates, 3% vs 81%).
      Five of the eight vanA phenotype E. faecium isolates and one of the 24 vanB
      phenotype E. faecium isolates were resistant to quinupristin/dalfopristin. The
      activity of rifampin was also species-specific, with E. faecium being markedly
      less susceptible to this agent than E. faecalis (MIC50, 16 vs 1 microgram/mL;
      MIC90, 64 vs 4 micrograms/mL). Our data suggest the potential of teicoplanin and
      quinupristin/dalfopristin as appropriate antimicrobial agents in the treatment of
      infections caused by vanB phenotype E. faecium. Penicillin, ampicillin, and
      rifampin alone, or preferably in combination with other agents, appear to be the
      most appropriate agents for the treatment of vancomycin-resistant E. faecalis
      infections in Taiwan.

PMID- 10063274
TI  - Gd(DTPA-BBA) as a contrast agent in magnetic resonance imaging in rats.
AB  - Gadolinium (III)-di(benzyl carbamoylmethyl) diethylenetrinitrilotriacetic acid
      [Gd(DTPA-BBA)] is a newly developed paramagnetic complex designed for use as a
      hepatobiliary-specific contrast agent. The purpose of this study was to examine
      the relaxivity, biodistribution, and magnetic resonance (MR) imaging
      characteristics of Gd(DTPA-BBA) in rats. Our results showed that the T1
      relaxivity of Gd(DTPA-BBA) (3.89 dm3/mmol/s in aqueous solution) was similar to
      that of Gd(III) diethylenetriamine-pentaacetate [Gd(DTPA)]2- (4.08 dm3/mmol/s)
      and Gd(III) benzyloxypropionicte-traacetate [Gd(BOPTA)]2- (4.40 dm3/mmol/s).
      Biodistribution studies indicated that Gd(DTPA-BBA) exhibited hepatobiliary and
      urinary elimination. In MR imaging studies, Gd(DTPA-BBA) provided biphasic
      enhancement of normal liver parenchyma, which was characterized by an initial
      steep increase in enhancement followed by a plateau. The initial relative
      enhancement (RE%) of the liver, at 1 minute after administration of 0.2 mmol/kg
      Gd(DTPA-BBA) was 113 +/- 19. The plateau RE% of the liver (48 +/- 13) occurred
      within 10 minutes and persisted for at least 60 minutes after injection of the
      contrast agent. In addition, Gd(DTPA-BBA) provided better RE% of the liver than
      [Gd(DTPA)]2-. The contrast RE% of liver abscess capsules reached a plateau within
      5 minutes after injection of 0.1 mmol/kg Gd(DTPA-BBA). Although the hepatic
      enhancement of Gd(DTPA-BBA) was inferior to that of [Gd(BOPTA)]2-, the results
      suggest that Gd(DTPA-BBA) has potential as an MR contrast agent for nonspecific
      and hepatobiliary uses.

PMID- 10063275
TI  - Ultrasonographic assessment of posterior heel pain.
AB  - To investigate the value of ultrasonography in the diagnosis of posterior heel
      pain, 68 patients with normal plain x-ray findings of the posterior heel
      underwent ultrasonographic examination with a 10-MHz linear array probe. The
      findings included Achilles tendinosis (31 patients), retrocalcaneal bursitis
      (12), superficial Achilles bursitis (7), soft tissue mass (7), Achilles tendon
      rupture (4), xanthoma (3), tenosynovitis of the flexor hallucis longus tendon
      (2), and negative findings (2). Sixteen of these patients underwent surgery after
      ultrasonographic examination. The surgical diagnoses were consistent with the
      ultrasonographic diagnoses in all cases. With high-resolution ultrasonography,
      pathologic conditions of the posterior heel can be readily differentiated.

PMID- 10063276
TI  - Disseminated Mycobacterium genavense infection in a patient with acquired
      immunodeficiency syndrome: first case report in Taiwan.
AB  - Mycobacterium genavense is a recently described fastidious mycobacterium
      identified as a pathogen causing disseminated infection in patients with advanced
      human immunodeficiency virus (HIV) disease. In this report, we describe the first
      reported case of disseminated M. genavense infection in a patient with acquired
      immunodeficiency syndrome (AIDS) in Taiwan. A 22-year-old Chinese man was found
      to be seropositive for HIV at age 18, in 1993. In 1997, he presented with
      abdominal pain, weight loss, low CD4 lymphocyte count, hepatomegaly, and
      generalized lymphadenopathy. Microscopic examination of a biopsy specimen from an
      inguinal lymph node showed both ill- and well-formed noncaseating granulomas.
      Numerous acid-fast bacilli were present in the histiocyte cytoplasm. Although the
      organism did not grow on conventional solid media used in our laboratory, two
      molecular biology techniques, including polymerase chain reaction (PCR) followed
      by sequencing of 16S rRNA, and PCR together with restriction enzyme fragment
      polymorphism analysis, confirmed the M. genavense infection. The patient's
      abdominal symptoms responded well to a chemotherapy regimen that included
      ethambutol, ciprofloxacin, and clarithromycin, and he survived more than 6 months
      after diagnosis. However, the lymphadenopathy was still present at his final
      follow-up. Our report indicates that disseminated infection with M. genavense
      should be added to the list of differential diagnoses of secondary infections in
      advanced AIDS patients in Taiwan.

PMID- 10063277
TI  - Successfully treated central nervous system Burkitt's lymphoma with minimal
      extraneural disease in a child.
AB  - Burkitt's lymphoma, the most common childhood non-Hodgkin's lymphoma, usually
      presents with abdominal tumors. Central nervous system (CNS) involvement in
      Burkitt's lymphoma is mostly secondary to advanced systemic disease, rarely with
      brain parenchymal lesions, and was previously recalcitrant to treatment. We
      report an unusual case of CNS Burkitt's lymphoma with minimal extraneural
      disease. This 10-year-old immunocompetent boy presented with increased
      intracranial pressure and seizures and was found to have multifocal intracerebral
      lesions on brain imaging studies. Cerebrospinal fluid studies confirmed the
      presence of Burkitt's lymphoma cells. Abdominal computed tomography showed
      bilateral nephromegaly with left intrarenal lesions that disappeared after three
      doses of intravenous dexamethasone. The patient was treated for 6.5 months
      according to the LMB 89 group C protocol of the French Pediatric Oncology
      Society. The response was brisk and complete. The patient has been disease free
      for more than 4 years, and is believed to be cured.

PMID- 10063278
TI  - Prognostic value of Doppler-derived mitral deceleration time in postinfarction
      patients with left ventricular ejection fractions of 35% or more.
AB  - Short Doppler-derived mitral deceleration time of early filling has been proved
      to be an independent predictor of poor prognosis in patients with left
      ventricular dysfunction. However, the prognostic value of Doppler-derived mitral
      deceleration time in postinfarction patients without overt left ventricular
      dysfunction is poorly understood. A total of 27 survivors of acute myocardial
      infarction with left ventricular ejection fractions of 35% or more, as determined
      by radionuclide ventriculography, were prospectively studied. Doppler study was
      performed 5 to 7 days after the index infarction. The patients were divided into
      two groups. Group A included 10 patients whose mitral deceleration time was 125
      msec or less and group B consisted of 17 patients whose mitral deceleration time
      was 125 msec or more. The two groups were similar in terms of age and gender
      distribution and there were no statistically significant differences in coronary
      risk factors, peak creatine kinase concentration, location of infarction, Killip
      classification, thrombolytic therapy, left ventricular ejection fraction, or
      medications. After a mean follow-up period of 30 months, the rate of congestive
      heart failure (New York Heart Association, NYHA, class II or above) was
      significantly higher in group A (5/10) than in group B (1/17) (p < 0.01). These
      results suggest that a short mitral deceleration time could be a useful early
      predictor of the potential development of future congestive heart failure in
      postinfarction patients with left ventricular ejection fractions of 35% or more.

PMID- 10063280
TI  - Evolution of cardiac surgery.

PMID- 10063279
TI  - Adrenal cancer with hypertension but low plasma renin and aldosterone.
AB  - Patients with malignant lesions of the adrenal gland may present with a syndrome
      of excess mineralocorticoids. Both primary hyperaldosteronism and excess
      mineralocorticoids other than aldosterone resulting from adrenal carcinoma have
      rarely been reported. In most patients with adrenal tumors secreting
      mineralocorticoids other than aldosterone, distant metastasis had already
      occurred at the time of diagnosis and the prognosis was poor. We present a rare
      case of adrenal cancer with hypertension in a patient with low plasma renin
      activity and a low plasma aldosterone concentration. The patient's blood pressure
      returned to normal after removal of the tumor. The patient is still alive and
      without recurrence 6 years after surgery. This case illustrates the value of
      thorough evaluation of hypertension and prompt surgical treatment for patients
      with adrenal cancer.

PMID- 10063281
TI  - Clinicopathologic study of lupus nephritis.
AB  - Needle biopsies of kidney were done in 35 cases of systemic lupus erythematosus
      (SLE) with renal lesions. The lupus nephritis were classified according to WHO
      classification and were correlated with response to therapy and prognosis.
      Detailed clinical features, routine haematological, biochemical tests (e.g.,
      serum urea, creatinine, total protein and albumin, cholesterol, etc), examination
      of urine (degree of proteinuria and cells) and occurrence of various auto
      antibodies e.g., antinuclear antibody (ANA), anti double stranded DNA (anti
      DsDNA) by enzyme immunoassay (EIA) method, LE cells and rheumatoid factor (RF)
      were studied in all cases. Clinically hypertension was present in 19 (54.3%)
      cases and nephrotic range of proteinuria was detected in 20 (57.2%) cases. ANA
      was found in 31 (88.5%) cases, anti DsDNA 24 (68.5%) and LE cells were detected
      in 25 (71.5%) cases. RF was detected in 2 (5.7%) cases. Histologically the most
      frequent lesions were class IV occurring in 15 cases (42.8%) with initial
      complete remission achieved only 4 cases by immunosuppressive therapy. Active
      lesions were also most frequent in this class. Class III lesions were found in 8
      (22.8%) cases with 6 cases had complete remission. The best prognosis was noted
      in class II cases with 4 out of 5 (14.3%) cases had complete remission. Class V
      lesions were found in 6 (17.2%) cases with complete remission achieved in 3
      cases. Only one patient presented with class VI lesion. RF positive cases had
      milder renal lesions.

PMID- 10063282
TI  - A study of the effects of pulsed electromagnetic field therapy with respect to
      serological grouping in rheumatoid arthritis.
AB  - The positive role of pulsed electromagnetic field (PEMF) therapy in rheumatoid
      arthritis (RA) is known. The differential role of serological status of patients
      in RA is also well known. This paper presents a study of the differential effects
      of PEMF therapy on the two serological groups of patients. The responses of the
      seropositive patients are found to be more subdued. Varying effects of the
      therapy in alleviating the different symptomatologies indicate that the
      rheumatoid factor (RF) is more resistant to PEMF.

PMID- 10063283
TI  - Cryptosporidium and HIV.
AB  - To study the importance of cryptosporidium as a diarrhoea causing pathogen (using
      stool samples), a cohort study was conducted from 14-9-1994 to 14-3-1995 on
      injecting drug users in Imphal. Stool samples were also collected from close
      contacts of the patients of human immunodeficiency virus (HIV) infected
      cryptosporidium diarrhoea cases and patients of paediatric medicine ward of
      Regional Institute of Medical Sciences (RIMS), Imphal. A total of 9 cases of
      cryptosporidium diagnosed out of 11 HIV infected diarrhoea cases and 2 out of 11
      personal contacts were found to be positive. Two cases with history of close
      contacts with HIV infected cryptosporidium diarrhoea cases were not suffering
      from diarrhoea. One out of 7 paediatric diarrhoea cases was found to be positive.
      Five out of 9 HIV infected cryptosporidial cases died within one month of
      diagnosis of cryptosporidium. The remaining 4 had improved and diarrhoea was
      controlled. One of the 4 did not show cryptosporidium any more in the stool
      sample.

PMID- 10063284
TI  - HIV infection among dental patients.
AB  - Oral manifestations may be the important indicators of ongoing human
      immunodeficiency virus (HIV) infection. Serum samples were collected from 100
      patients repeatedly attending dental outpatients' department of SV Medical
      College and SVRR Hospital, Tirupati and tested for the presence of HIV
      antibodies. HIV 1 antibodies were detected in one person, the seropositivity rate
      being 1%.

PMID- 10063285
TI  - Paediatric HIV infection: a brief review.

PMID- 10063286
TI  - Citizen charter versus medical ethics and health legislation.

PMID- 10063287
TI  - Sezary syndrome--a case report.

PMID- 10063288
TI  - Craniopharyngioma presenting as cavernous sinus thrombosis.

PMID- 10063289
TI  - A variant of fracture dislocation of Monteggia.

PMID- 10063290
TI  - Medical profession--points to ponder.

PMID- 10063291
TI  - Separate obstetricians from abortionists.

PMID- 10063292
TI  - Hypothyroidism with multiple serous effusions.

PMID- 10063293
TI  - Distance learning for health professionals' education.

PMID- 10063294
TI  - Oils for the heart.

PMID- 10063295
TI  - Awareness of hypertension among a north Indian population.
AB  - Developing countries are going through a demographic transition. Non-communicable
      diseases like hypertension are emerging in epidemic proportions. Education and
      awareness among people is the key to reduce the burden of the disease. To see the
      levels of awareness and characteristic of aware and unaware hypertensives, 7630
      employees in Shimla town were screened for hypertension. Hypertension was
      detected in 2535 cases of which 559 (22.05%) were aware. The aware hypertensives
      were predominantly symptomatic and had higher age and blood pressure than the
      unaware hypertensives. The aware hypertensives were predominantly overweight.
      This low level of awareness highlights the need for a comprehensive hypertension
      education programme to be taken up at the national level.

PMID- 10063296
TI  - Comparison between two different modes of oxygen therapy during immediate
      postoperative period following mitral commisurotomy.
AB  - Hypoxaemia is a common postoperative problem after thoracotomy. Oxygen therapy
      with continuous monitoring by pulse oximetry should be a routine practice. This
      study was conducted to compare the efficacy between nasal cannula and ventimask
      for post-thoracotomy oxygen supplementation on 20 patients divided into 2 groups
      of 10 each undergoing closed mitral commisurotomy. The study period was of 5
      months duration from March to July, 1996. The mean oxygen saturation remained
      above 98% in both the groups receiving oxygen either by nasal cannula or
      ventimask. As there was adequate oxygenation, the cost benefit ratio favours the
      use of nasal cannula for routine postoperative oxygen supplementation in the
      closed mitral commisurotomy patients.

PMID- 10063297
TI  - Clinical significance of pituitary apoplexy.
AB  - A retrospective analysis of 280 cases of pituitary adenoma operated on over a
      period of 10 years from 1985-94 revealed 15 cases (5.3%) presenting with
      apoplexy, though there were 48 cases in which haemorrhage in pituitary adenoma
      was confirmed at operation. In the apoplectic group all but one had abrupt onset
      of severe headache. Seven of these 15 patients had diminution of vision and
      ocular motility defects were detected in 5 patients. There were 5 patients of
      amenorrhoea/galactorrhoea syndrome and 2 had acromegalic features. In the
      remaining 8 patients retrospective analysis failed to reveal any conclusive
      evidence of pituitary dysfunction. Trans-sphenoidal surgery was performed in 9
      cases and the rest had transcranial surgery. Visual acuity loss improved in most
      of the affected patients, residual ocular motility defects were mild. Urgent
      trans-sphenoidal surgery to decompress the expanding mass seems to be the
      preferred mode of surgery.

PMID- 10063298
TI  - Choice of cooking oils--myths and realities.
AB  - In contrast to earlier epidemiologic studies showing a low prevalence of
      atherosclerotic heart disease (AHD) and type-2 dependent diabetes mellitus (Type
      2 DM) in the Indian subcontinent, over the recent years, there has been an
      alarming increase in the prevalence of these diseases in Indians--both abroad and
      at home, attributable to increased dietary fat intake. Replacing the traditional
      cooking fats condemned to be atherogenic, with refined vegetable oils promoted as
      "heart-friendly" because of their polyunsaturated fatty acid (PUFA) content,
      unfortunately, has not been able to curtail this trend. Current data on dietary
      fats indicate that it is not just the presence of PUFA but the type of PUFA that
      is important--a high PUFA n-6 content and high n-6/n-3 ratio in dietary fats
      being atherogenic and diabetogenic. The newer "heart-friendly" oils like
      sunflower or safflower oils possess this undesirable PUFA content and there are
      numerous research data now available to indicate that the sole use or excess
      intake of these newer vegetable oils are actually detrimental to health and
      switching to a combination of different types of fats including the traditional
      cooking fats like ghee, coconut oil and mustard oil would actually reduce the
      risk of dyslipidaemias, AHD and Type-2 DM.

PMID- 10063299
TI  - Nalidixic acid induced pseudotumour cerebri in children.
AB  - Nalidixic acid, the quinolone frequently used in the treatment of acute
      dysentery, is now emerging as an important cause of pseudotumour cerebri in
      infants and young children. A study of 20 such cases showed that all the patients
      had received a higher than recommended dose of nalidixic acid and that 85% of
      them were given the drug unnecessarily (i.e., for acute watery diarrhoea). A high
      concentration of the drug in the commercial preparations as well as the lack of
      awareness about this among doctors, especially the general practitioners, is the
      possible contributory factor leading to this situation. A simple measure of
      bringing down the concentration of nalidixic acid in the available preparations
      and sticking to oral rehydration solution alone in the treatment of acute watery
      diarrhoea, can bring down the incidence of this condition.

PMID- 10063300
TI  - Simple closure of perforated duodenal ulcer.
AB  - A study was undertaken to evaluate the efficacy of simple closure followed by
      drug therapy in cases of perforated duodenal ulcer and to identify the risk
      factors in relation to the mortality. The male to female ratio was 5:1. Of the
      patients 59.2% were up to 50 years of age, while 40.8% were above the age of 50
      years. Of the patients 47% were admitted 24 hours after the onset of peritonitis.
      All these patients were surgically treated with simple closure of the perforation
      with omental patch. Nine patients expired leading to 7.5% mortality. The risk
      factors identified for mortality were age 60 years and above, presence of shock
      on admission and delayed presentation. The mortality is directly related to the
      number of risk factors present in a given patient. At the time of discharge the
      patients were advised to take orally famotidine 40 mg at bed time for a period of
      8 weeks. Eighty-one patients could be followed up and Visick grading was done.
      Sixty-two patients were in grade I, 11 in grade II, 3 in grade III and 5 in grade
      IV. The results indicate that simple closure followed by drug therapy is
      acceptable treatment for perforated duodenal ulcer.

PMID- 10063301
TI  - The ultimate panacea--relief of pain.

PMID- 10063302
TI  - Medicine in the Internet: should you be a participant?

PMID- 10063303
TI  - Splenic tuberculosis--a case report.

PMID- 10063304
TI  - Cystic nephroma--a case report and review of literature.

PMID- 10063305
TI  - Breast filariasis--an unusual presentation.

PMID- 10063306
TI  - Lipoleiomyoma of uterus--an uncommon lesion.

PMID- 10063307
TI  - T cell subsets in chronic hepatitis B and the effect of prednisolone withdrawal
      and interferon alpha-2b.
AB  - OBJECTIVES: The evaluations of the pathogenetic roles of cell mediated immunity
      and of the preventive effect for disease progression with interferon(IFN)
      treatment in patients with chronic active hepatitis-B(CAH-B) are the objectives
      of this study. METHODS: Thirty-two patients with CAH-B were treated with
      interferon alpha-2b(IFN alpha-2b) with prednisolone withdrawal and 30 control
      patients were treated with conventional hepatotonics for 6 months. Peripheral
      total T cell fractions and T cell subsets of the patients with CAH-B, treated
      with IFN alpha-2b with prednisolone withdrawal, were examined 1 month before
      administration of prednisolone, and compared with 12 normal controls for
      assessing the potential role of cellular immunity in the development of CAH-B. To
      estimate the effectiveness of IFN therapy for the patients with CAH-B, levels of
      various liver function tests, HBsAg, anti-HBs, HBeAg, anti-HBe, HBV DNA, anti-HCV
      and others were assessed for the treatment group and compared with control
      patients at pre- and post-treatment period each. RESULTS: The value of CD4 was
      significantly lower in patients with CAH-B than normal controls (36.3 +/- 7.7% vs
      42.1 +/- 5.7%, p < 0.05) and the value of CD8 was significantly higher in
      patients with CAH-B than normal controls (30.6 +/- 10.3% vs 24.3 +/- 5.2%, p <
      0.05) before prednisolone administration. The patients in responder group (n =
      26) had significantly lower CD4 cells compared with normal controls, but non
      responders (n = 6) did not have. The levels of liver function test(LFT) in the
      patients with IFN alpha-2b treatment with prednisolone withdrawal were not
      different from the control patient group at pretreatment, but significantly lower
      than control patient group's after treatment, regardless of response to IFN alpha
      2b treatment with prednisolone withdrawal. CONCLUSIONS: The cellular immunity of
      the host may have a potential role in the pathogenesis of chronicity of hepatitis
      B infection. IFN alpha-2b treatment with prednisolone withdrawal may be regarded
      as one of the effective treatment modalities for the inhibition of disease
      progression in patients with CAH-B.

PMID- 10063308
TI  - Changes in the evolution of the antigenic profiles and morphology during coccoid
      conversion of Helicobacter pylori.
AB  - OBJECTIVES: The significance of the coccoid forms of H. pylori is still
      controversial and the questions of whether these forms are viable and infective
      or degenerative are still open. We induced conversion from rod to coccoid forms
      and studied morphological changes and antigenic evolutions during this conversion
      and, thereby, elucidated the viability of coccoid forms. METHODS: The H. pylori
      strain (C001) used for Western blotting was isolated from the patient with
      gastric cancer. The antigenic evolution during coccoid conversion of H. pylori
      was studied by Western blotting, using different sera from thirty patients known
      to be culture positive. These sera were used to reveal the total antigens of the
      strain cultured for 2 days (100% rod) and 15 days (> 99% coccoid). After SDS
      PAGE, with 10% separating gel of total antigens (rod and coccoid), transblotting
      (Trans-Blot electrophoretic cell, Bio-Rad) was taken onto a nitrocellulose
      membrane (Bio-Rad). Then, the blots, with human sera diluted at 1/100, were
      developed with color reaction by goat serum anti-human IgG with alkaline
      phosphatase and BCIP. RESULTS: The antigenic profiles were not changed in 46.7%
      (14/30 cases) and were changed in 53.3% (16/30 cases) during coccoid conversion.
      Antigenic fractions changed during coccoid conversion were protein band at 120
      kDa and band at 35 kDa, and were not detected in coccus forms. The rest of the
      profiles were identical between rod and coccoid forms. The protein which
      disappeared include CagA (120 kDa) and porin, or adhesin (35 kDa). The
      morphological changes during coccoid conversion were U shaped at day 7, doughnut
      shaped at day 9 and full coccoid at day 15. CONCLUSIONS: The results showed that
      coccoid forms of H. pylori retain cellular structures similar to rod form, and
      some of the antigens (CagA and porin) disappeared during coccoid conversion.
      Therefore, coccoid form might be viable and represent one of the stages of H.
      pylori biological cycle.

PMID- 10063309
TI  - Effect of Helicobacter pylori infection on antral gastrin and somatostatin cells
      and on serum gastrin concentrations.
AB  - OBJECTIVES: Helicobacter pylori infection induces selective reduction of the
      number of antral D-cells and results in abnormal regulation of serum gastrin
      secretion. The purpose of this study was to investigate the relationship between
      H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers
      of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum
      gastrin concentrations were compared between 37 patients with (29 with duodenal
      ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with
      duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were
      measured using the radioimmunoassay technique. Antral mucosal biopsy specimens
      were examined using immunohistochemical staining with antibodies specific for
      gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland
      were counted. RESULTS: Fasting serum gastrin concentrations were significantly
      higher in patients with H. pylori infection compared to patients without
      infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p < 0.001). The number of G
      cells per gastric gland was similar in infected and uninfected patients (7.1 +/-
      3.1 vs 7.3 +/- 3.9, respectively, p > 0.5). The number of D-cells was
      significantly lower in patients with H. pylori infection than in uninfected
      patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6,
      respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly
      higher in infected patients compared with uninfected patients for both gastric
      and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001).
      CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection
      induces reduction of the number of antral D-cells. The resulting relative
      hypofunction of the inhibitory action of D-cells against G-cells may be
      responsible for increased serum gastrin secretion.

PMID- 10063310
TI  - Altered renal expression of nitric oxide synthase isozymes in spontaneously
      hypertensive rats.
AB  - OBJECTIVES: The present study was aimed at exploring whether the pathogenesis of
      hypertension is related with an altered expression of nitric oxide synthase (NOS)
      isozymes, i.e., bNOS, iNOS and ecNOS. METHOD: By Western blot analysis, the
      expression of NOS isozymes were determined in the kidney isolated from
      spontaneously hypertensive rats (SHR) and their normotensive control, Wistar
      Kyoto rats (WKY). The NOx (nitrite/nitrate) contents were also determined in the
      kidney and plasma. RESULTS: The plasma NOx was significantly increased in SHR
      compared with that in WKY. The basal level of NOx was higher in the medulla and
      cortex of the kidney in SHR compared with that in WKY rat. bNOS proteins were
      expressed higher in the outer medulla and cortex, and iNOS proteins were higher
      in the inner medulla, outer medulla and cortex in SHR. ecNOS expression did not
      significantly differ between the SHR and WKY. CONCLUSIONS: These results indicate
      that the NO generation may not be impaired, but rather increased. It is likely
      that the increased expression of NOS isozymes is a counter-reactive phenomenon
      secondary to the increased blood pressure in this model of hypertension.

PMID- 10063311
TI  - Drug-resistant pulmonary tuberculosis in a tertiary referral hospital in Korea.
AB  - OBJECTIVES: To estimate the resistance rate and to correlate the clinical
      characteristics of resistant tuberculosis with the patients of pulmonary
      tuberculosis who were referred to the university hospital. METHODS: We
      prospectively performed sensitivity tests for all patients who were diagnosed as
      active tuberculosis by sputum smear or sputum culture from January, 1995 to June,
      1996. Patients profile, previous treatment history, patterns of drug resistance,
      initial chest films and other clinical findings were analysed. RESULTS: Overall,
      24(26.0%) of the 92 patients had resistance to at least one drug and 8(8.6%) had
      resistance to isoniazid(INH) and rifampin(RFP). Among the 66 patients without
      previous tuberculosis therapy, 11(16.6%) were drug-resistant and 2(3.0%) were
      multi-drug resistant. Among the 26 patients with previous therapy, 13(50.0%) were
      drug-resistant and 6(23.0%) were multi-drug resistant. For all 92, resistance to
      INH was most common (19.5%), followed by RFP (9.7%) and ethambutol (9.7%). Drug
      resistance was significantly high in previously treated patients and in cavity
      positive patients. Treatment failure was also high in previously treated patients
      with resistant tuberculosis. In patients with primary resistance, treatment
      failure was not observed. CONCLUSION: Sensitivity tests are strongly recommended
      in all culture positive patients with previous therapy but, in patients with
      primary resistance, sensitivity tests are not required. Proper combination
      chemotherapy should be given under careful surveillance.

PMID- 10063312
TI  - Role of nitric oxide in the pathogenesis of diabetic nephropathy in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: Several reports suggest that enhanced generation or actions of nitric
      oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration
      and hyperperfusion that occurs in early diabetes. However, the precise role of
      altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The
      present study was aimed at investigating the role of nitric oxide in the
      pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin
      induced diabetic rats. METHODS: To evaluate the role of NO in diabetic
      hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable
      metabolic products of NO and protein expressions of three isoforms of nitric
      oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also
      investigated renal hemodynamic changes, such as glomerular filtration rate (GFR)
      and renal plasma flow (RPF), in responses to acute and chronic administration of
      NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and
      control rats. RESULTS: Diabetic rats exhibited significantly elevated plasma and
      urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total
      excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than
      controls. Insulin and L-NAME treatment prevented the increases in plasma and
      urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three
      isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex,
      whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were
      significantly elevated in diabetic rats, and acute and chronic inhibition of NO
      synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR
      and RPF) in diabetic rats, respectively. CONCLUSIONS: NO synthesis was increased
      due to enhanced NOS expression in diabetic rats, and chronic NO blockade
      attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In
      addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute
      NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest
      that excessive NO production may contribute to renal hyperfiltration and
      hyperperfusion in early diabetes.

PMID- 10063313
TI  - The relationship between cisplatin-induced apoptosis and p53, bcl-2 and bax
      expression in human lung cancer cells.
AB  - OBJECTIVES: Given the roles of bcl-2, bax and p53 in apoptosis, we investigated
      the effect of their expression on the response to cisplatin in order to
      understand the molecular events of cisplatin-resistance in lung cancers. METHODS:
      Three parental human lung cancer cell lines (PC9, PC14 and H69) and their in
      vitro selected cisplatin-resistant sublines were examined. Cells treated with
      cisplatin were processed for acridine orange and ethidium bromide staining and
      DNA gel electrophoresis for the morphologic detection of apoptosis. The
      endogenous levels of bcl-2, bax and p53 protein expression in lung cancer cells
      were assessed by Western blot analysis and DNA of polymerase chain reaction
      amplified exon 5 to 8 of p53 gene was directly sequenced. RESULTS: H69, which had
      bcl-2 expression, p53 mutation and decreased expression of p53 and bax, was
      relatively resistant to cisplatin and delayed and reduced apoptosis. Although
      apoptosis was markedly reduced in cisplatin-resistant sublines compared to their
      parental cells, there were no significant differences in the expression of p53,
      bcl-2 and bax. CONCLUSIONS: Cisplatin-resistance was associated with the reduced
      cellular susceptibility to apoptosis. Cancer cells with the natural expression of
      bcl-2 and p53 mutation may be more resistant to cisplatin and less susceptible to
      apoptosis.

PMID- 10063314
TI  - The effects of transferring tumor suppressor gene p16INK4A to p16INK4A-deleted
      cancer cells.
AB  - OBJECTIVES: p16 is known to be an important tumor suppressor gene and is also
      called MTS1 (multiple tumor suppressive gene 1). Especially in the case of non
      small cell lung cancer, it was not expressed in more than 70% of cell lines
      examined. To determine changes in cell-cycle related proteins and the tumorigenic
      effect, we, therefore, transfected p16INK4A gene into lung cancer cell lines.
      METHODS: We transfected p16INK4A gene into lung cancer cell lines which do not
      express p16 protein. We evaluated the effect by clonogenic assay and observed the
      changes of cell-cycle related proteins. RESULTS: The newly-expressed p16 formed a
      complex with cdk4, and phosphorylated pRB was decreased, although cyclin D1 and
      pRB:cyclin D1 complex were unchanged. Clonogenic assay after selection with G418
      showed that, in the cell lines transfected with p16, tumorigenicity was
      significantly less than in the control. CONCLUSION: These results suggest that
      the p16INK4A gene can be a candidate for gene therapy in cases of NSCLC in which
      p16INK4A gene is inactivated.

PMID- 10063315
TI  - Expression of p53 protein in rheumatoid arthritis synovium. An
      immunohistochemical analysis.
AB  - OBJECTIVES: Mutation of p53 may play a role in manifestation of rheumatoid
      arthritis synovium, but several studies on p53 expression in synovial tissues of
      rheumatoid arthritis showed conflicting results. We investigated the amount and
      pattern of p53 positive cells in rheumatoid arthritis synovium, in comparison
      with osteoarthritis synovium, by using immunohistochemistry with two other
      monoclonal antibodies for p53. METHODS: Synovial tissues from 9 patients with
      rheumatoid arthritis and 5 patients with osteoarthritis were examined for p53
      expression by immunohistochemistry with 2 monoclonal antibodies for p53, DO-1 and
      DO-7. Histologic features of inflammation were also scored and compared with p53
      expression. RESULTS: There was no significant difference between inflammatory
      scores in both groups. In the synovial tissues of rheumatoid arthritis patients,
      p53 positive cells were detected in 3 out of 9 samples(33%) and p53 expressions
      were restricted to inflammatory mononuclear cells, but synovial lining cells,
      subsynovial fibroblast-like cells and vascular endothelial cells were p53
      negative. p53 expressions in osteoarthritis synovial tissues as control were
      observed in 2 out of 5 samples(40%) and the amount and pattern of p53 positive
      cells were comparable to those seen in rheumatoid arthritis synovial tissues.
      There was no demonstrable correlation between the synovial tissues of both groups
      with respect to inflammation scores and expression of p53 protein. CONCLUSION:
      Our findings suggest that altered p53 expression may not play a significant role
      in the manifestation of rheumatoid arthritis synovium. However these data need to
      be strengthened by increasing the number of samples and molecular biology
      approaches.

PMID- 10063316
TI  - Clinical analysis of Behcet disease: arthritic manifestations in Behcet disease
      may present as seronegative rheumatoid arthritis or palindromic rheumatism.
AB  - OBJECTIVES: To analyze arthritic manifestations in Behcet disease, which is one
      of the most common manifestations of Behcet disease. METHODS: Among the patients
      who visited the Rheumatology Division, Keimyung University Dongsan Medical
      Center, Taegu, Korea from March 1997 to February 1998, 35 patients, with more
      than 3 months follow-up, were compatible for the diagnosis of Behcet disease
      according to the Shimizu criteria, after exclusion of uncertain or possible
      Behcet cases. The presence of various manifestations was evaluated. Regarding the
      joint manifestations, the involved joint, signs and the pattern of the articular
      symptoms were examined. Basic laboratory tests, HLA studies and simple radiologic
      studies were done. RESULTS: All 35 patients had evident, recurrent, painful oral
      ulcers by the study definition. Genital ulcers were found in 29%, skin lesions in
      77%, uveitis in 9%, gastrointestinal ulcerations in 6% and vascular
      manifestations in 6%. Joint manifestations appeared in 97%. Knee(91%), proximal
      interphalangeal (53%) and metacarpophalangeal joints(21%) were the main sites.
      Tenderness was prominent in 91% and swelling in 44%. Polyarticular presentation
      was found in 47%. In most cases (76.4%), the articular symptom was short-lasting.
      C-reactive protein was likely to be positive in active Behcet disease. HLA B51
      was positive in 46%. CONCLUSIONS: In Behcet disease, various manifestations can
      be found. The arthritic manifestation seems quite common. It may present as
      seronegative rheumatoid arthritis. Otherwise, it may present as palindromic
      rheumatism.

PMID- 10063317
TI  - Pylephlebitis associated with appendicitis.
AB  - Pylephlebitis usually occurs secondary to infection in the region drained by the
      portal venous system. A most common antesecent focus of infection is
      diverticulitis and the most common blood isolate is E. coli (54%), followed by
      Proteus mirabilis (23%). Overall mortality is 32% and most of the patients who
      had died had severe sepsis prior to the initiation of antibiotic therapy. We
      describe a case of pylephlebitis which had appendicitis and consequent septic
      thrombosis of the portal vein and its branches, with dissemination of infection
      to the liver. The patient had recovered due to timely antibiotic treatment alone
      and resulted in complete resolution. Early diagnosis and treatment are basic to a
      favorable clinical course.

PMID- 10063318
TI  - Changes of glomerular basement membrane components in Vacor-induced diabetic
      nephropathy.
AB  - OBJECTIVES: The thickening of the glomerular basement membrane in rats after
      Vacor ingestion was examined by electron microscopy. This study was performed to
      elucidate which biochemical components changed in the glomerular basement
      membrane after Vacor-induced diabetic glomerulopathy. METHODS:
      Immunohistochemical analyses of type IV collagen, laminin, fibronectin and
      chondroitin sulfate proteoglycan were performed. A single dose of Vacor
      (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by
      orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56
      days after administration. RESULTS: Mild thickening of the glomerular basement
      membrane was evident 7 days after Vacor administration, and the width of the
      glomerular basement membrane was more than twice that of normal controls at 28
      and 56 days. Significantly increased expressions of type IV collagen, laminin,
      fibronectin and neutral polysaccharide in the thickened glomerular basement
      membrane were noted 14 to 56 days after administration, and a mildly increased
      expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days.
      CONCLUSION: These abnormally increased glomerular basement membrane components
      might be part of what causes diabetic nephropathy after Vacor administration.

PMID- 10063319
TI  - A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a
      patient with rheumatoid arthritis and renal insufficiency.
AB  - Most reports on serious MTX toxicity have focused on hepatic abnormalities, while
      other effects, including hematologic reactions, have not been emphasized. We
      experienced a case of pancytopenia secondary to MTX therapy in a patient with RA
      and renal insufficiency. A 67-year-old woman with a 12-year history of active
      seropositive RA that was a response to non-steroidal anti-inflammatory drugs,
      hydroxychloroquinine and intra-articular steroid injections, had been followed up
      and was diagnosed as early chronic renal failure in October, 1993. Recently,
      because of significant morning stiffness and polyarthralgia, the decision was
      made to institute MTX treatment. This was begun as a single oral dose of
      5mg/week. After 2 doses, the patient was admitted to the hospital with general
      weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count
      1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1
      mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal,
      but the serum albumin level was 2.7 g/dl. The patient subsequently developed
      fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and
      intravenous prophylactic antibiotic therapy were required. Her condition was
      improved. In summary, Low-dose MTX-related adverse hematologic side effects,
      including fatal pancytopenia, are rare but are a cause of increasing concern in
      patients with RA and renal insufficiency. Close monitoring of associated risk
      factors, particularly impaired renal function, should be mandatory for all
      patients who are receiving MTX therapy.

PMID- 10063320
TI  - A case of primary leiomyosarcoma of the lesser omentum.
AB  - Leiomyosarcoma is a rare tumor that originates in the smooth muscle, usually in
      the gastrointestinal tract, the retroperitoneum and the genitourinary tract. The
      omentum has been rarely reported as a primary site of occurrence with
      leiomyosarcoma. A 72 year-old woman, with palpable mass on the left upper
      quadrant of abdomen and weight loss, was admitted to St. Paul's Hospital.
      Abdominal CT scan showed a 12 x 8 x 8 cm-sized cystic mass in the left upper
      quadrant of the abdomen. Endoscopic ultrasonography showed a large cystic mass
      between the stomach and the liver, which was 1.6 cm length in wall thickness.
      Laparotomy and resection of the mass was performed. A 12 x 8 x 8 cm-sized mass,
      originated from the lesser omentum, was discovered near the lesser curvature of
      the stomach. Microscopic examination revealed spindle-shaped cells with 7-8
      mitoses per high power field. She was diagnosed as primary leiomyosarcoma
      originated from the lesser omentum.

PMID- 10063321
TI  - Successful treatment with ganciclovir for cytomegalovirus duodenitis following
      allogenic bone marrow transplantation.
AB  - Cytomegalovirus(CMV) disease is a major cause of morbidity and mortality in
      immunocompromised patients. CMV enteritis should be considered when nausea and
      vomiting continue 3 to 4 weeks after bone marrow transplantation(BMT). The
      treatment of CMV enteritis is not well established. We report a CMV duodenitis
      patient following allogenic bone marrow transplantation. The patient had
      prolonged nausea and vomiting for 5 weeks after bone marrow transplantation and
      CMV duodenitis was diagnosed by the gastroduodenoscopic mucosal biopsy which
      showed cytomegalic cells. Ganciclovir treatment for 3 weeks resulted in the
      resolution of symptoms and promoted healing of the lesion. The patient was free
      of CMV infection until 288 days after allogenic BMT without maintenance
      ganciclovir treatment.

PMID- 10063322
TI  - Hyperimmunoglobulin E-recurrent infection syndrome in a patient with juvenile
      dermatomyositis.
AB  - A 13-year-old girl presented with multiple skin abscesses. She was diagnosed as
      having juvenile dermatomyositis (DM) at the age of 7 years. She had suffered from
      recurrent skin infections, atypical pruritic dermatitis and pneumonia since the
      age of 8 years. Bacteriologic and fungal cultures for skin abscesses and oral
      mucosa were positive S. aureus and C. albicans, respectively. Chemotactic defect
      in peripheral blood neutrophils was observed. The level of serum IgE was markedly
      elevated, and anti-S.aureus specific IgE was found. A diagnosis of
      hyperimmunoglobulin E-recurrent infection syndrome (HIE) was made and she was
      successfully treated with surgical drainage and antibiotics. To our knowledge,
      this is the first case report of HIE in a patient with juvenile dermatomyositis.

PMID- 10063323
TI  - [Increased body mass index increase and insulin resistance parameters in
      dyslipidemia. Risk and positive correlation in essential obesity].
AB  - BACKGROUND: Obesity is frequently characterized by hyperinsulinemia with insulin
      resistance, tendency to impaired glucose tolerance and by impaired lipidic
      picture. The relationship existing between some obesity parameters i.e. BMI and
      weight excess (EP) regarding ideal weight calculated according Lorenz's formula
      and main parameters both of insulin-resistance and lipidic picture can be
      interesting. METHODS: 58 obese subject (10 M e 48 F) age 38 +/- 6.2 years (mean
      +/- DS) with BMI 34.3 +/- 5.3 and EP 33.7 +/- 15; they didn't suffer from
      hypertension and diabetes; they was subjected to an OGTT and evaluation of
      glycemia and insulinemia after 0', 60', 90', 120', 150', 180'. Moreover an
      assessment of lipidic state (cholesterol, triglyceride, HDL, LDL) was carried
      out. Glycemia and insulinemia with respective areas under curve (AUC glyc. e AUC
      ins.) and increases (AUCI glyc. e AUCI ins.) were compared with BMI and EP for
      searching relationship. The same was done for lipidic state. RESULTS: BMI was
      found positively related with glycemia after 0' (r = 0.3043, p < 0.05) 60' (r =
      0.3465, p < 0.05) 120' (r = 0.2895, p < 0.05) with AUC glyc. (r = 0411, p < 0.01)
      and AUCI glyc. (r = 0.276, p < 0.05), with insulinemia after 0' (r = 0.365, p <
      0.01) 60' (r = 0.350, p < 0.01) and with AUC ins. (r = 0.272, p < 0.05). HDL is
      negatively (r = -0.307, p < 0.05) instead of triglyceride positive related (r =
      0.338, p < 0.05) with BMI. EP is positively related with glycemia after 0' (r =
      0.376, p < 0.01), 60' (r = 0.362, p < 0.01), 120' (r = 0.290, p < 0.05), with AUC
      glyc. (r = 0.422, p < 0.01), with insulinemia after 0' (r = 0.512, p < 0.01), 60'
      (r = 0.473, p < 0.01) with AUC ins. (r = 0.420, p < 0.01) and AUCI ins. (r =
      0.354, p < 0.01). Triglyceride was positively related (r = 0.365 p < 0.01) with
      EP. CONCLUSIONS: These relationships suggest that BMI and EP can be considered as
      indicators not only of obesity degree, but also of hyperinsulinemia and, to a
      lesser extent, dyslipidemia severity.

PMID- 10063324
TI  - [Gliclazide and metformin combination in patients with type 2 diabetes.
      Preliminary data].
AB  - BACKGROUND: This preliminary study is aimed at the evaluation of the efficacy and
      tolerability of combined therapy with gliclazide and metformin in the treatment
      of patients with type 2 diabetes mellitus inadequately controlled with maximal
      doses of gliclazide. METHODS: A prospective, uncontrolled study, with a follow-up
      of 3 months, was performed in two Outpatient Diabetes Care Units. Fifty-seven
      patients affected by type 2 diabetes for at least 5 years, aged 61.0 +/- 3.4
      years, with a duration of diabetes of 9.2 +/- 3.9 years, Body Mass Index (BMI)
      30.5 +/- 3.7 kg/m2, previously treated with gliclazide 240 mg/day, and with HbA1c
      > 8.5%, were studied. The patients were treated with gliclazide 120 mg/day and
      metformin 1500 mg/day for 3 months; HbA1c, 24-hour glycosuria, and fasting and
      post-prandial glycaemia, were determined at the beginning and at the end of the
      study. RESULTS: After a 3-month treatment, a reduction of fasting and post
      prandial glycaemia, glycosuria (15.0 +/- 5.3 versus 5.7 +/- 4.0 g/l, p < 0.01),
      and HbA1c (9.9 +/- 1.1 versus 8.4 +/- 1.0%, p < 0.01) was observed, while no
      significant changes occurred in body weight. The treatment was generally well
      tolerated. CONCLUSIONS: In conclusion, the combination of gliclazide and
      metformin, which could theoretically show some advantages over the association of
      glibenclamide and metformin with regards to lipid and haemorheologic profiles,
      resulted to be effective and well tolerated in patients with type 2 diabetes
      inadequately controlled with sulphonylurea monotherapy.

PMID- 10063325
TI  - [Benign thyroid nodules in the elderly. Medical treatment].
AB  - BACKGROUND AND AIM: Benign thyroid nodules are a frequent pathology in the
      general population and in particular in the aged, but their treatment is still
      controversial. The percentage by which volume and/or the number of nodules is
      reduced using L-thyroxine treatment reported in the literature varies widely:
      from 9 to 68%. The aim of this study was to study the therapeutic efficacy of
      thyroxine treatment in the aged. METHODS: A retrospective study was performed in
      105 elderly out-patients (mean age 68 +/- 6 years) suffering from thyroid nodules
      forming part of a population of 7452 thyroid patients from central Italy
      attending the 2nd Medical Clinic at "La Sapienza" University of Rome from 1986 to
      1994. Other diseases which might influence treatment were excluded in all
      subjects. Thyroid hormones, TSH and antithyroid antibodies were assayed using RIA
      techniques; patients also underwent ultrasonography of the gland, 131I thyroid
      captation with scintigraphy and cytological analysis using fine needle
      aspiration. Patients were treated with L-thyroxine (75-150 micrograms/day) and
      controlled after 6, 12 and 24 months. No collateral effects were reported.
      RESULTS: The majority of patients (some 85%) remained stationary; just under 10%
      improved and only a few showed a deterioration of symptoms. CONCLUSIONS: Medical
      therapy continues, in the authors' opinion, to be the first choice in the
      treatment of benign thyroid nodules also in elderly patients owing to its easy
      management, low cost and scarce collateral effects.

PMID- 10063326
TI  - [A case of familial Bardet-Biedl syndrome (obesity, slight mental retardation,
      polydactyly, retinitis pigmentosum and renal failure) with insulin-resistant
      diabetes mellitus].
AB  - A case of familial Bardet-Biedl syndrome (BBS) in a 64-year-old woman is
      presented; it is characterized by abdominal obesity (BMI: 38.28; WHR: 0.98),
      slight mental retardation, polydactyly, pigmentary retinopathy and moderate renal
      failure, with insulin-resistant diabetes mellitus and severe inflammation of the
      left limb with necrosis of the last toe (the sixth) of the left foot. Four
      brothers and sisters of the patient presented the same syndrome. The patient had
      had healthy offsprings. The review of current literature indicates that BBS is a
      genetic autosomal recessive disease, formerly grouped with Laurence-Moon-Biedl
      syndrome but today considered as a separate entity. It is characterized by
      obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or
      polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism in males,
      and renal structural abnormalities or functional impairment. Extra- and
      intrafamilial variability of expressivity and severity of the various clinical
      manifestations was reported, among affected families and also in the same family.
      BBS is a rare but important syndrome, that should be known by the endocrinologist
      and the specialist in internal medicine, because it has an adverse prognosis,
      with early onset of blindness, insulin-resistant diabetes mellitus and severe
      renal impairment. Renal failure is a frequent cause of death early in life, even
      in the infant-juvenile years.

PMID- 10063327
TI  - [A particular case of iodine-induced hypothyroidism].
AB  - A surplus of iodine taken through drugs or food can cause a functional thyroidal
      deficiency, especially if there are pre-existent alterations in the gland. The
      case described of a young woman with a iodine-induced hypothyroidism without
      goitre due to an excessive trans-cutaneous/trans-mucous absorption of iodine in
      sea-bath salts. The woman, aged 32, showed a symptomatology characterized by
      asthenia, ponderal increase, constipation and bradypsychia. The thyroid appears
      normal after echography and scintigraphy. Iodized sea-bath salts have been used
      for three months in a hot water bath for a slimming effect. A complete regression
      is noticed with their suspension after one year. An excessive supply of iodine
      can even if rarely cause a hypothyroidism with/without goitre, because of an
      intrinsic defect in the mechanism of the organic link which permits a persistent
      Wolff-Chaickoff effect. A genetic predisposition is supposed and also a higher
      frequency in patients with a preceding thyroiditis, Basedow disease or Hashimoto
      disease. Particular attention should be given to a differential diagnosis in case
      of hypothyroidism in young women with a normal thyroid and negative antibodies.
      It is clear that a careful pharmacological anamnesis is essential as well as a
      careful anamnesis on the way of life.

PMID- 10063328
TI  - The genetics of cystic fibrosis.

PMID- 10063329
TI  - alpha 1-antitrypsin deficiency.

PMID- 10063330
TI  - Genetics of sarcoidosis.

PMID- 10063332
TI  - Introduction to the mechanism of obstructive sleep apnoea and snoring.

PMID- 10063331
TI  - Genetics of chronic obstructive pulmonary disease and disseminated
      bronchiectasis.

PMID- 10063333
TI  - Autocontinuous positive airway pressure in the diagnosis and treatment of
      obstructive sleep apnoea.

PMID- 10063334
TI  - Non-CPAP treatment of obstructive sleep apnoea.
AB  - Obstructive sleep apnoea is a frequently occurring disease that can have
      important consequences including disabling hypersomnolence and sleepiness as well
      as cardiovascular diseases like hypertension. Treatment modalities are, however,
      limited. The efficacy of nasal continuous positive airway pressure (CPAP) stands
      out, but not all patients can tolerate this treatment or be compliant with it.
      Efficacious alternative therapies are still remarkably few in number. It is
      demonstrated and concluded that only patients with mild forms of the disease can
      currently be considered for non-CPAP treatments. Patients with predominantly
      breathing pattern abnormalities can be cured with medical therapy. Those with
      predominantly upper airway collapse and with mildly elevated critical closing
      pressure can be treated with surgical procedures such as
      uvulopalatopharyngoplasty (UPPP). The exact indications for electrical
      stimulation of the hypoglossal nerve are still to be determined, although
      preliminary results seem to be promising for well-selected patients.

PMID- 10063335
TI  - What is the evidence that obstructive sleep apnoea is an important illness?
AB  - Obstructive sleep apnoea (OSA) is described by some authors as a potentially
      lethal disease and by others as an almost harmless condition. Excessive daytime
      sleepiness, neuropsychological dysfunction, altered quality of life,
      cardiovascular disease (systemic and pulmonary hypertension, cardiac arrhythmias,
      stroke and ischaemic heart disease) and increased mortality have been described
      as OSA complications. There is little argument that OSA may determine sleepiness,
      alter cognitive functions, and worsen quality of life, although with great
      interindividual variability: this should induce OSA to be considered an important
      illness per se, since sleepiness in OSA was shown to lead to important
      consequences, like road traffic accidents. Besides, OSA may interact with
      coexisting cardiac and respiratory disease and favour the appearance of heart and
      respiratory failure. Therefore, OSA is certainly also worth careful consideration
      as an important aggravating factor of other diseases. The evidence that
      obstructive sleep apnoea is an independent risk factor for cardiovascular
      complications other than owing to the recurrent transient blood pressure surges
      associated with apnoeas during sleep, and for an increased mortality is more
      conflicting. More studies are necessary to identify which characteristics of
      obstructive sleep apnoea may be considered important markers of its severity and
      as risk factors for different possible complications.

PMID- 10063336
TI  - Monitoring respiratory muscles.
AB  - The respiratory system consists of two main parts, the lung and the ventilatory
      pump. The latter consists of the bony structure of the thorax, the central
      respiratory controllers, the inspiratory and expiratory muscles, and the nerves
      innervating these muscles. Respiratory muscle fatigue occurs when respiratory
      muscle endurance is exceeded. Muscle fatigue is defined as a condition in which
      there is a reduction in the capacity for developing force and/or velocity of a
      muscle, resulting from muscle activity, and which is reversible by rest. The
      respiratory muscles are somewhat difficult to assess and the techniques employed
      are still relatively primitive. The most important methods of respiratory muscles
      function assessment are: 1) the vital capacity manoeuvre, which depends on
      maximum inspiratory and expiratory effort by the muscles and may be a useful
      indicator of respiratory muscle function; 2) radiological screening has been
      proposed for the detection of diaphragm paralysis. This may be helpful if the
      paralysis is unilateral, but bilateral paralysis is difficult to detect; and 3)
      respiratory muscles strength may be assessed with either voluntary or
      nonvoluntary manoeuvres. The function of the inspiratory muscles is assessed with
      3 voluntary dependent manoeuvres. They are the so called Muller manoeuvre (or
      maximal inspiratory pressure), the sniff test and the combined test. All these
      three manoeuvres generate a pressure that is a reflection of complex interactions
      between several muscle groups since the efforts produce different mechanisms of
      activity of inspiratory and expiratory muscles. Two techniques are presently
      employed to assess diaphragm function, not being dependent on the patient's
      motivation: electrical phrenic nerve stimulation and cervical magnetic
      stimulation. Since it is less painful, magnetic cervical stimulation overcomes
      some of the difficulties encountered during electrical stimulation. With these
      two techniques recordings of diaphragmatic force are possible, and at the same
      time useful information about the conduction time of both phrenic nerves can be
      obtained.

PMID- 10063337
TI  - Protective ventilatory strategy for ARDS: physiological evaluation of the
      clinical trials.

PMID- 10063338
TI  - Mechanical ventilation in acute respiratory distress syndrome: evolving concepts.

PMID- 10063339
TI  - Sense of effort and dyspnoea.

PMID- 10063340
TI  - Measurement of dyspnoea.

PMID- 10063341
TI  - The language of breathlessness.

PMID- 10063342
TI  - Dyspnoea in chronic obstructive pulmonary disease.

PMID- 10063343
TI  - Dyspnoea and asthma.

PMID- 10063344
TI  - Dyspnoea: some physiological and practical aspects for treatment.

PMID- 10063345
TI  - Epidemiology of tuberculosis in Europe.
AB  - The regular decline in tuberculosis (TB) notification rates observed in several
      industrialized countries over the past two decades has levelled off or reversed
      in recent years. The aim of the present study is to review the epidemiological
      situation in Europe (updated to 1996), focusing on the annual risk of TB
      infection, mortality, notifications and age distribution of new smear-positive
      cases. Epidemiological data were obtained from national statistical reports
      produced by the Ministry of Health, the Global Tuberculosis Programme and
      Monitoring Project of the World Health Organization and the Euro TB Report on the
      feasibility study of Surveillance of Tuberculosis in Europe. The increasingly
      high mortality rates notified by the Baltic States, Romania, the Russian
      Federation and the countries previously belonging to the USSR and a few countries
      of the former Yugoslavia have been attributed to late patient detection and low
      cure rates, compounded, in some cases, with a lack of first-line drugs, resulting
      in the use of suboptimal regimens. In addition, higher death rates than in the
      general population have been described in risk groups, including prisoners and
      exprisoners, alcohol addicts and the unemployed. The analysis of notification
      rates and trends in Europe indicates that a stabilization in the number of
      notified cases or even a new decline had been achieved where efficient TB control
      programmes had been established or revitalized (e.g. in the majority of Western
      European and in several Central European countries).

PMID- 10063346
TI  - Tuberculosis in patients infected with the human immunodeficiency virus.

PMID- 10063347
TI  - Nontuberculous mycobacteria and human infections.

PMID- 10063348
TI  - Evidence-based medicine: a means of improving clinical outcome and cost-benefit
      ration.
AB  - Evidence-based medicine (EBM) is a new way of conceiving clinical practice based
      on the need to both improve the approach to the patient's care and rationalize
      the costs. EBM is thus defined as "the conscientious, explicit and judicious use
      of current best evidence in making decisions about the care of individual
      patients". To realize this project a cultural change is mandatory, involving
      doctors, health planners, and users, whose empowerment seems pivotal. Reasoning
      in terms of efficacy or even better of cost-benefit ratio will certainly improve
      the clinical outcome and the allocation of resources.

PMID- 10063349
TI  - Diagnosis and treatment of asthma. What's true?

PMID- 10063350
TI  - Diagnosis and treatment of chronic obstructive pulmonary disease: evidence-based
      medicine.
AB  - Chronic obstructive pulmonary disease (COPD) is a very common disorder caused
      primarily by cigarette smoking. Recently national and international guidelines
      were produced in order to standardize the management of the disease. It became
      apparent that only a few items in these documents are based on evidence-based
      studies. Diagnosis should be made in relation to the definitions, symptoms, signs
      and routine investigation. Spirometry is essential for the diagnosis of COPD. The
      two well documented modes of treatment, namely cessation of smoking and long-term
      oxygen therapy are discussed in detail.

PMID- 10063351
TI  - Evidence-based aspects of lung volume reduction surgery.

PMID- 10063352
TI  - Mucoactive drugs in the management of chronic obstructive pulmonary disease.
AB  - In chronic obstructive pulmonary disease (COPD), mucus hypersecretion is
      considered one of the main symptoms. Recently the natural history of COPD has
      been better defined and chronic mucus hypersecretion is now viewed as linked to
      the acceleration of forced expiratory volume in one second (FEV1) decline and not
      merely as an "innocent disorder". In the past, mucoactive drugs were claimed to
      treat mucus hypersecretion. However, since most mucoactive drugs have not been
      evaluated in large clinical studies, European Respiratory Society and American
      Thoracic Society COPD guidelines discourage their use for treatment of COPD
      patients. Clinical trials have been often disappointing because improvement in
      lung function has been adopted as the main outcome, despite bronchial obstruction
      in COPD patients being frequently irreversible or poorly reversible. Thus, goals
      for treatment in COPD patients should include not only improvement in lung
      function, but also clinical symptoms and quality of life. Moreover, to rightly
      allocate these drugs in COPD management and to try to modify the natural history
      and progression of COPD, mucus hypersecretion might require treatment in the
      first stage of the disease. In conclusion, mucoactive treatments for chronic
      obstructive pulmonary disease patients should be re-evaluated in the future in
      patients selected according to demographic factors such as degree and
      reversibility of bronchial obstruction due to mucus hypersecretion, patient
      smoking habits and other socioeconomic parameters which have proved to be
      relevant to the progression of the disease, according to the latest
      recommendations for guidelines on clinical trials of mucoactive drugs in chronic
      bronchitis and chronic obstructive pulmonary disease.

PMID- 10063353
TI  - Combination therapy of fasudil hydrochloride and ozagrel sodium for cerebral
      vasospasm following aneurysmal subarachnoid hemorrhage.
AB  - Fasudil hydrochloride is a new type of intracellular calcium antagonist,
      different from the calcium entry blockers that are commonly employed for clinical
      use. Since September 1995, the combination of fasudil hydrochloride and ozagrel
      sodium, an inhibitor of thromboxane A2 synthesis, has been used to treat 60
      patients at risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
      The effectiveness of this combination therapy was investigated by comparison with
      the outcome of 57 patients previously treated with only ozagrel sodium. The
      combination therapy was significantly more effective (p < 0.01) in reducing the
      incidence of low density areas on computed tomography scans, and reduced, but not
      significantly, the occurrence of symptomatic vasospasm. The combination therapy
      of fasudil hydrochloride and ozagrel sodium has superior effectiveness over only
      ozagrel sodium in treating patients at risk of vasospasm after aneurysmal
      subarachnoid hemorrhage.

PMID- 10063354
TI  - In vitro inhibition of binding of tumor necrosis factor (TNF)-alpha by monoclonal
      antibody to TNF receptor on glioma cell and monocyte.
AB  - The use of monoclonal antibodies to the tumor necrosis factor (TNF) receptors,
      the TNF-p55 receptor (TNF-p55R) and the TNF-p75 receptor (TNF-p75R), was
      evaluated to reduce the effects of TNF caused by binding to TNF-p75R. Competitive
      binding of anti-TNF-p55R (mAbp55R) and anti-TNF-p75R monoclonal antibodies
      (mAbp75R) with iodine-125-labeled TNF-alpha to GL-9 glioma cells and U937
      histiocytic lymphoma cells was evaluated. The effects of mAbp55R and mAbp75R on
      the growth suppression by TNF-alpha of GL-9 cells and TNF-alpha production in
      U937 cells were also examined. mAbp75R bound to U937 cells competitively with TNF
      alpha and suppressed TNF-alpha production by U937, but had no effect on the
      growth inhibition of GL-9 human glioma cell by TNF-alpha in vitro. These findings
      suggest that co-administration of TNF-p75R antagonist with TNF-alpha may decrease
      the toxicity of TNF-alpha administration resulting in a better therapeutic
      result.

PMID- 10063355
TI  - Ultramicroscopic structures of the leptomeninx of mice with communicating
      hydrocephalus induced by human recombinant transforming growth factor-beta 1.
AB  - An experimental model of communicating hydrocephalus was developed based on
      intrathecal injection of human recombinant transforming growth factor-beta 1
      (hrTGF-beta 1) in the mouse. To clarify the mechanism of this hydrocephalus
      model, the ultrastructure of the leptomeninx in the process of ventricular
      dilation was examined in C57/BL6 mice injected intrathecally with 60 ng of hrTGF
      beta 1. The leptomeninx was examined at various periods after injection by light
      and electron microscopy. Immunostaining for fibroblasts and macrophages was also
      performed. Leptomeninx within a week after injection showed that the thin
      cytoplasmic processes of leptomeningeal cells formed a laminated structure with a
      meshwork, which was almost the same as the controls. In the second week, many
      cells with a round nucleus appeared in the leptomeninx. Immunohistochemically,
      these cells were positive for anti-fibroblast antibody and negative for anti-Mac
      1 and anti-macrophage BM-8 antibodies. Three weeks later, the laminated structure
      was disrupted and abundant deposition of collagen fibers was found in the inter
      cellular space of the leptomeninx. Such inter-meningeal fibrosis would disturb
      cerebrospinal fluid flow in the mouse leptomeninx and cause slowly progressive
      ventricular dilation.

PMID- 10063356
TI  - Large and giant middle to lower basilar trunk aneurysms treated by surgical and
      interventional neuroradiological methods.
AB  - Treatment of large and giant aneurysms of the basilar artery remains difficult
      and controversial. Three large or giant aneurysms of the lower basilar artery
      were treated with a combination of surgical and interventional neuroradiological
      procedures. All patients underwent the balloon occlusion test with hypotensive
      challenge (blood pressure reduced to 70% of the control value). The third patient
      did not tolerate the test. In the first patient, both vertebral arteries were
      occluded through a craniotomy. In the second patient, both the aneurysm and the
      basilar artery were occluded by detached balloons. In the third patient, one
      vertebral artery was occluded by surgical clipping and the other by detached
      helical coils and fiber coils. In spite of anti-coagulation and anti-platelet
      therapy, postoperative thrombotic or embolic ischemia occurred in the second and
      third patients. Fibrinolytic therapy promptly corrected the ischemic symptoms,
      but the second patient developed hemorrhagic complications at the craniotomy area
      2 hours later. At follow-up examination, the first patient had only 8th cranial
      nerve paresis, the second patient who had a hemorrhagic complication was bed
      ridden, and the third patient had no deficit. Interventional occlusion requires a
      longer segment of the parent artery compared to surgical occlusion of the parent
      artery and might cause occlusion of the perforating arteries. However, selected
      use of various coils can occlude only a short segment of the parent artery. Thus,
      the postoperative management of thromboembolic ischemia after the occlusion of
      the parent artery is easier using the interventional technique.

PMID- 10063357
TI  - Combined carotid endarterectomy and coronary artery bypass graft.
AB  - Atherosclerosis is a generalized disease which afflicts a considerable number of
      patients in both the carotid and coronary arteries. Although the risk of stroke
      or death use to combined carotid endarterectomy (CEA) and coronary artery bypass
      graft (CABG) is thought to be higher than that of each individual operation, the
      combined procedure is generally preferred over staged operations to treat such
      patients. We performed the combined procedure safely with the aid of
      intraoperative portable digital subtraction angiography (DSA). This report
      describes our experience with the operative strategy of simultaneous CEA and
      CABG. Ninety CEA and 404 CABG were carried out between January 1989 and December
      1997. A total of six patients received the combined procedure with the aid of
      intraoperative DSA; they were studied retrospectively. Postoperative mortality
      and morbidity after the combined procedure was 0%. In the combined procedure,
      neurological complications are difficult to detect after CEA because the patient
      must be maintained under general anesthesia and extracorporeal circulation during
      the subsequent CABG. However, intraoperative DSA can confirm patency of the
      internal carotid artery and absence of flap formation after CEA, and the CABG can
      be performed safely. Intraoperative portable DSA between CEA and CABG is helpful
      in preventing perioperative stroke in the combined procedure.

PMID- 10063358
TI  - Significance of acute cerebral swelling in patients with sylvian hematoma due to
      ruptured middle cerebral artery aneurysm, and its management.
AB  - A retrospective study of 75 patients treated surgically for ruptured middle
      cerebral artery (MCA) aneurysm within 48 hours evaluated clinical grade at
      admission, secondary development and management of cerebral swelling associated
      with space-occupying hematoma, cerebral infarction caused by vasospasm,
      development of hydrocephalus, and clinical outcome. Clinical grade at admission
      was significantly better in patients without than in those with hematoma (p <
      0.01). Twenty-seven patients with sylvian hematoma caused by ruptured MCA
      aneurysm often developed ipsilateral cerebral swelling in the early period after
      subarachnoid hemorrhage. Seventeen of these patients developed serious cerebral
      swelling and received barbiturate therapy. Nine of these 17 patients had good
      outcome, but six patients died of cerebral swelling. The incidence of
      hydrocephalus was significantly higher in patients with than in those without
      hematoma (p < 0.01). The incidence of infarction was more pronounced in patients
      with sylvian hematoma. Clinical outcome was significantly better in patients
      without than in those with sylvian hematoma (p < 0.01). Development of cerebral
      swelling in patients with sylvian hematoma due to ruptured MCA aneurysm has a
      significant effect on outcome, and improvements in management are required.

PMID- 10063359
TI  - Clinical importance of c-Met protein expression in high grade astrocytic tumors.
AB  - The clinical importance of the expression of c-Met protein, the receptor of
      hepatocyte growth factor/scatter factor, was evaluated in neuroepithelial tissue
      tumors. c-Met immunohistochemistry was performed using the streptavidin-biotin
      peroxidase complex method with anti-c-Met polyclonal antibody. Specimens were
      classified as c-Met negative (< 30%) or c-Met positive (> or = 30%) according to
      the proportion of immunopositive cells under microscopic examination. All c-Met
      positive cases occurred in high grade astrocytic tumors, not in other
      neuroepithelial tissue tumors. Most c-Met-positive astrocytic tumors were
      classified histologically as high grade tumors. Epidermal growth factor-receptor
      (EGFR) and MIB-1 immunohistochemistry were also performed for high grade
      astrocytic tumors. Survival analysis was performed for patients with these tumors
      with variables including c-Met positivity, EGFR positivity, and MIB-1 labeling
      index. Positivity of c-Met was independent from EGFR positivity and MIB-1
      labeling index, and the c-Met-positive group showed a significant shorter
      survival (p < 0.05). c-Met immunopositivity may be a parameter of biological
      aggressiveness in high grade astrocytic tumors. Examination of c-Met expression
      in astrocytic tumors provides significant clinical information, especially as a
      prognostic factor.

PMID- 10063360
TI  - Rupture mechanism of a thrombosed slow-growing giant aneurysm of the vertebral
      artery--case report.
AB  - A 76-year-old male developed left hemiparesis in July 1991. The diagnosis was
      thrombosed giant vertebral artery aneurysm. He showed progressive symptoms and
      signs of brainstem compression, but refused surgery and was followed up without
      treatment. He died of rupture of the aneurysm and underwent autopsy in March
      1995. Histological examination of the aneurysm revealed fresh clot in the
      aneurysmal lumen, old thrombus surrounding the aneurysmal lumen, and more recent
      hemorrhage between the old thrombus and the inner aneurysmal wall. The most
      important histological feature was the many clefts containing fresh blood clots
      in the old thrombus near the wall of the distal neck. These clefts were not lined
      with endothelial cells, and seemed to connect the lumen of the parent artery with
      the most peripheral fresh hemorrhage. However, the diameter of each of these
      clefts is apparently not large enough to transmit the blood pressure of the
      parent artery. Simple dissection of the aneurysmal wall by blood flow in the
      lumen through many clefts in the old thrombus of the distal neck may be involved
      in the growth and rupture of thrombosed giant aneurysms of the vertebral artery.

PMID- 10063361
TI  - Secondary glioblastoma remarkably reduced by steroid administration after
      anaplastic transformation from gliomatosis cerebri--case report.
AB  - A 45-year-old female presented with gliomatosis cerebri manifesting as
      hemiballismus-like involuntary movement in the arm, motor weakness in the leg,
      and hypesthesia in her left side. Computed tomography showed only diffuse
      swelling of the right cerebral hemisphere, but T2-weighted magnetic resonance
      imaging revealed a diffuse lesion spreading from the right thalamus to the
      temporal, parietal, and occipital lobes on the same side. No abnormal enhancement
      was recognized. Cerebral angiography showed no specific finding. A right
      occipital lobectomy was performed to confirm the diagnosis of gliomatosis
      cerebri. Anaplastic transformation was recognized 5 months later. The disease did
      not resolve with radiation or interferon administration, but steroid therapy
      achieved remarkably effective tumor regression. The patient died due to
      pneumonia. Autopsy showed the features of diffuse glioblastoma. Steroid therapy
      may be an effective treatment for gliomatosis cerebri before the terminal stage.

PMID- 10063362
TI  - Contralateral deafness following unilateral suboccipital brain tumor surgery in a
      patient with large vestibular aqueduct--case report.
AB  - A 68-year-old female developed contralateral deafness following extirpation of a
      left cerebellopontine angle epidermoid cyst. Computed tomography showed that
      large vestibular aqueduct was present. This unusual complication may have been
      caused by an abrupt pressure change after cerebrospinal fluid release, which was
      transmitted through the large vestibular aqueduct and resulted in cochlear
      damage.

PMID- 10063363
TI  - Pneumocephalus associated with ethmoidal sinus osteoma--case report.
AB  - A 35-year-old female suffered sudden onset of severe headache upon blowing her
      nose. No rhinorrhea or signs of meningeal irritation were noted. Computed
      tomography (CT) with bone windows clearly delineated a bony mass in the right
      ethmoid sinus, extending into the orbit and intracranially. Conventional CT
      demonstrated multiple air bubbles in the cisterns and around the mass in the
      right frontal skull base, suggesting that the mass was associated with entry of
      the air bubbles into the cranial cavity. T1- and T2-weighted magnetic resonance
      (MR) imaging showed a low-signal lesion that appeared to be an osteoma but did
      not show any air bubbles. Through a wide bilateral frontal craniotomy, the
      cauliflower-like osteoma was found to be protruding intracranially through the
      skull base and the overlying dura mater. The osteoma was removed, and the dural
      defect was covered with a fascia graft. Histological examination confirmed that
      the lesion was an osteoma. The operative procedure resolved the problem of air
      entry. CT is superior to MR imaging for diagnosing pneumocephalus, by providing a
      better assessment of bony destruction and better detection of small amounts of
      intracranial air.

PMID- 10063364
TI  - Rethinking the Tuskegee Syphilis Study. Nurse Rivers, silence and the meaning of
      treatment.

PMID- 10063365
TI  - Full circle. The nurse-midwifery careers of Elizabeth Berryhill and Gabriela
      Olivera.

PMID- 10063366
TI  - Nurse-midwives, the mass media, and the politics of maternal health care in the
      United States, 1925-1955.

PMID- 10063367
TI  - Frances Elisabeth Crowell and the politics of nursing in Czechoslovakia after the
      first world war.
AB  - The firmly entrenched, negative attitude regarding the nurse in Czechoslovakia
      was a major deterrent to the development of nursing education in that country
      after the First World War. Social work was the culturally acceptable form of
      caring activity for educated women who perceived nursing as a hospital function
      performed by the religious orders and the less educated. Alice Masaryk, an
      innovative force in addressing social welfare problems after the war, reinforced
      this perception. Despite her early investigative experience in social welfare in
      American settlements before the war, Masaryk gave no indication that she was
      aware of the recent progress in the development of nursing in America. Her
      attitude fostered the indecisiveness of the ministers who lacked a clear
      understanding of nursing and who were reluctant to make any innovative changes
      that would modernize the profession. Furthermore, older physicians were content
      with the current nursing situation and did not share younger physicians' visions
      of a public health team that included well-educated nurses. Crowell had to
      negotiate within this political and cultural environment where the major figures
      struggled against proposed changes that may have seemed not only expensive, but
      also unsettling to their way of life. She recognized the necessity of respecting
      the Czech position and cooperating with them in attaining an amicable solution.
      Her educational and professional background, and the European cultural insights
      she had gained during her years in the U.S. supported her well in meeting this
      challenge.

PMID- 10063368
TI  - Vivian Bullwinkel. Sole survivor of the 1942 massacre of Australian nurses.

PMID- 10063369
TI  - Refuge and rescue. Jewish nurse refugees and the International Council of Nurses,
      1947-1965.

PMID- 10063370
TI  - High ideals versus harsh reality. A historical analysis of mental health nursing
      in Dutch asylums, 1890-1920.

PMID- 10063371
TI  - Asylum nursing and institutional service. A case study of the south of England,
      1861-1881.

PMID- 10063372
TI  - Entering the professional domain. The making of the modern nurse in 17th century
      France.

PMID- 10063373
TI  - [Heterotopic pancreatic tissues--a rare differential diagnostic problem in
      stomach tumors].

PMID- 10063374
TI  - [Skeletal scintigraphy in Paget disease and bone metastases from bronchial
      carcinoma: differential diagnostic aspects].

PMID- 10063375
TI  - [Nephrolithiasis in "disk-variant" cross-over renal dystopia. Report of a case].
AB  - Renal dystopia is a frequent urogenital anomality. Renal dystopia encloses pelvic
      kidney or malascending kidney, but also rare anomalities like renal duplication
      or crossed renal dystopia. These allotopias are often diagnosed on routine
      examination of the urogenital system. We report a case with fused crossed renal
      dystopia on the left with atypical symptoms of nephrolithiasis and give a summery
      of the embryological origin.

PMID- 10063376
TI  - [Case report: gastric duplication--two cases and review of the literature].

PMID- 10063377
TI  - [Atraumatic Clostridium infection with fulminant psoas rhabdomyolysis and liver
      abscess].

PMID- 10063378
TI  - The advantages of limited resection vs. suture in the primary management of
      penetrating lung war wounds.
AB  - The aim of this study was to prove the advantage of the limited lung resection
      vs. suture in the primary management of penetrating lung war wounds. A
      prospective clinical study was presented about the results of primary surgical
      treatment of 50 injured with penetrating lung wounds, operated at the Military
      Medical Academy. The patients were divided into two groups: primary group was
      comprised of the wounded with limited resection, and the control group of the
      wounded with lung suture. Among the observed parameters, special attention had
      been paid to the specific postoperative complications, observed in 48% of the
      wounded from the group with lung suture (p < 0.01). The results of the
      investigation have demonstrated the significant advantage of limited resection
      vs. suture, and the method itself revealed all the features of radical and
      definite management of severe lung injuries. Precise indications for the use of
      both treatment methods are given.

PMID- 10063379
TI  - [Coronarography in the diagnosis of left atrial thrombosis].
AB  - Thrombosis of left atrium is frequent in the patients with mitral defect.
      Systemic embolism that generates by separated thrombus parts is a possible
      complication during the disease. Echocardiography is routinely used in the
      diagnosis of left atrial thrombosis. On the basis of angiographic experience, we
      have set the hypothesis: coronary angiography has a great sensitivity, but small
      specificity in the diagnosis of left atrial thrombosis. The presence of thrombus
      in left atrium was analyzed in 60 operated patients with mitral valve disease.
      During the surgery, thrombus was found in 13, and not found in 47 patients.
      Coronary angiography was preoperatively performed in all patients. In 9 out of 13
      patients with intraoperatively observed left atrial thrombus, thrombus was also
      found by angiography. In 47 patients thrombus was found neither intraoperatively,
      and in 45 nor by angiography. The sensitivity of angiography in the diagnosis of
      left atrial thrombosis is 69%, specificity is 97%, and the accuracy is 90%.
      Positive index of anticipation is 81%, and negative index of anticipation is 91%.

PMID- 10063380
TI  - [Radiotherapy of local recurrence of rectal carcinoma].
AB  - In retrospective, non-randomized study were analyzed 45 patients with local
      recurrences of rectal carcinoma treated by combined external beam radiotherapy
      (EBRT) and "High dose rate (HDR) remote afterloading" brachytherapy in the period
      from January 1st, 1988 to May 1st, 1988. Depending on the localization of the
      local recurrent disease, 20 patients were with vaginal relapse, 13 with vaginal
      and presacral, 9 with perineal and 3 with presacral and rectal. Combined
      radiotherapy was applied as follows: 33 patients (73.3%) had EBRT with
      endovaginal brachytherapy, 3 (6.7%) EBRT plus intraluminal brachytherapy and 9
      (20%) patients EBRT plus interstitial brachytherapy. Techniques with 3 and 4
      field for EBRT were used and doses ranged 45-65 Gy with convenient fractionation
      were applied, combined with the doses ranged 15-35 Gy for brachytherapy.
      Radiotherapy was planned according to the computer tomography cross image on
      simulator with computer planning. Complete regression of the tumor was observed
      in 19 patients (42.2%), and partial in 23 patients (51.1%). Median follow-up
      period was 34 months (8-72). Acute radiation adverse effects were registered in
      32 patients, and late sequels in 6 (13.3%). Overall 3-year survival rate was 54%
      and disease-free survival rate was 34% in the same period.

PMID- 10063381
TI  - [Propofol and thiopentone in elective cesarean section: effect on the mother and
      neonate].
AB  - All the anesthetics used for induction of anesthesia in cesarean section cross
      the placenta and can induce neonatal depression. The aim of this investigation
      was to compare intravenous anesthetics propofol and thiopentone as induction
      agents in patients scheduled for elective cesarean section and studying of their
      affection of mothers and new-born children. A total of 40 female patients were
      scheduled for elective cesarean section. They were randomly divided in two equal
      groups, each of them was to receive different anesthetic: propofol 2.5 mg/kg (n =
      20) or thiopentone 5 mg/kg (n = 20). Orotracheal intubation was facilitated with
      suxamethonium 1.5 mg/kg. Anesthesia was maintained by controlled ventilation with
      mixture of nitrous oxide and oxygen (50%:50%) and pancuronium 4 mg. After
      extraction of the foetus, anesthesia was maintained with mixture of nitrous oxide
      and oxygen (70%:30%), fentanyl 0.15-0.20 mg and pancuronium 1-2 mg. At the end of
      operation, competitive neuromuscular block was antagonised with neostigmine.
      There were no significant differences among the groups, as regards age, body
      weight and height, ASA classification grade and week of gestation. Following
      induction of anesthesia, a significantly greater decrease of blood pressure and
      heart rate was found in the propofol group, when compared with the patients in
      thiopentone group. During the induction and maintenance of anesthesia, the
      frequency of adverse effects was greater in thiopentone, than in propofol group
      (6/20 versus 2/20 patients). There was no significant difference between the
      groups when induction-delivery (l-D) interval was concerned. The new-borns from
      the propofol group had significantly higher Apgar score in the 1st minute (8.35)
      and 5th minute (9.25), than the new-borns in thiopentone group (7.90 and 8.90,
      respectively).

PMID- 10063382
TI  - [Total allergen-specific IgE antibodies in the serum and skin reactivity induced
      by a mixture of pollens in allergic individuals].
AB  - Skin puncture test is fast and precise method for revealing IgE-mediated allergen
      hypersensitivity. In the diagnosis of pollinosis and other atrophic diseases,
      expensive tests for revealing the allergen-specific IgE antibodies in the serum
      are frequently inaccessible. The subject of our investigation was how and if the
      skin test with mixture of pollen could replace the expensive in-vitro method in
      diagnostic procedure. In 41 patients with pollinosis were performed skin tests by
      the mixture of pollen of grass, weeds and trees (produced by Torlak Institute,
      Belgrade) and determined the concentration of overall and allergen-specific IgE
      serum (EIA, enzyme immuno-assay, Pharmacia Uppsala; RAST Phadesim, multidisk,
      Pharmacia). Obtained results pointed out that the sex of investigated subjects
      did not influence the size of skin reaction in case when the pollen mixture
      (grass, weed or trees) was used. With high significance rate was established that
      in skin puncture test, just the size of the reaction, defined by 5 mm papule or
      larger, indicated the hypersensitive person. We consider that this can be taken
      as the diagnostic criterion and replace in-vitro method for determination of
      allergen-specific IgE antibodies in serum. Also, overall IgE of serum positively
      correlated (p < 0.05) with the size of skin reaction only in the persons with
      extremely high concentrations (RAST class 4) allergen-specific IgE antibodies in
      serum.

PMID- 10063383
TI  - [Efficacy of continuous ambulatory peritoneal dialysis in treatment of children
      with end-stage renal insufficiency].
AB  - Three children (2 girls and 1 boy) with end-stage renal failure were put in
      program of continuous ambulatory peritoneal dialysis in the period of 2.5 years
      (January 1995-September 1997). The age of the children at the treatment onset was
      5-12 years. One of three children died due to cardiovascular failure after six
      month treatment. Two out of three children had a total of 8 episodes of
      peritonitis in the period of 37 months during the treatment with peritoneal
      dialysis. The incidence of peritonitis occurrence in our patients was one episode
      in 4 patients/months. Most frequent cause for peritonitis occurrence was
      Staphylococcus aureus in 50% of isolated bacteria. Obtained results in peritoneal
      equilibration test revealed that the transport and ultrafiltration rate of
      peritoneal membrane decreased after recurrent peritonitis episodes.

PMID- 10063384
TI  - [Genetic basis of Parkinson's disease: are we changing our thinking?].

PMID- 10063385
TI  - [Recognition of cardiovascular drug interactions in general medical practice].

PMID- 10063386
TI  - [Hematopoietic stem cells--biology and therapeutic use].

PMID- 10063387
TI  - [Ten new lessons in hemostasis].

PMID- 10063388
TI  - [Viral hepatitis G--current knowledge].

PMID- 10063389
TI  - [Chronic encapsulated intracerebral hematoma].
AB  - Radiological-morphologic features of chronic intracerebral hematomas are observed
      by computed tomography (CT) and magnetic resonance (MR), and in angiographic
      examination are particularly characterized by the absence of pathologic
      vascularization. The patient, aged 61, with confirmed diagnosis of encapsulated
      intracerebral hematoma, treated at the Clinic of Neurology and Clinic of
      Neurosurgery of the Military Medical Academy was presented. The patient was
      released after recovery, and was consequently followed up in an outpatient
      department by a neurosurgeon. Six-month follow-up demonstrated the regression of
      the clinical signs of the disease, as well as the alterations in CT and MR images
      in the same sense.

PMID- 10063390
TI  - [Therapeutic embolization of the spleen].
AB  - Spleen embolization is a method of percutaneous occlusion of instrasplenic
      vascular network, by which is achieved a partial embolization of arterial
      branches with the convenience of controlled circulation reduction. Reduction
      achieved in this way corrects clinical and laboratory symptoms of hypersplenism
      and improves hematologic status in the diseases of lymphopoietic tissues where
      splenectomy is otherwise the therapeutic solution. This method had been applied
      experimentally, and afterward clinically since 1973, but with numerous
      complications and incidents. The authors had discussed those complications,
      commented the method development, so as physiopathologic and hemodynamic
      circumstances, and considering them, the method had become efficacious and safe.
      Using the modified methodologic principle, they had performed the first
      transcatheter spleen embolization at the Institute for Radiology of Military
      Medical Academy in the patient with liver cirrhosis, hypersplenism, splenomegaly
      and the signs of portal hypertension. The authors described the applied methods,
      postintervention effects and clinical and laboratory condition in six months
      after the intervention. Considering the positive clinical and laboratory results,
      the authors are of the opinion that the method of transcatheter spleen
      embolization is useful therapeutic alternative to splenectomy.

PMID- 10063391
TI  - [Dislocation of the Lisfranc joint in a military skier].
AB  - The case of Lisfranc's dislocation in soldiers-skiers has been presented. The aim
      of the study is to realize the role of skiing equipment in generation of the
      injuries in soldiers-skiers. Early therapeutic intervention provides good
      results.

PMID- 10063392
TI  - Children, youth, and families: building on the cultural strengths of Hispanic and
      Latino communities.

PMID- 10063393
TI  - Elevated asthma morbidity in Puerto Rican children: a review of possible risk and
      prognostic factors.
AB  - Latino children represent a significant proportion of all US children, and asthma
      is the most common chronic illness affecting them. Previous research has revealed
      surprising differences in health among Latino children with asthma of varying
      countries of family origin. For instance, Puerto Rican children have a higher
      prevalence of asthma than Mexican American or Cuban American children. In
      addition, there are important differences in family structure and socioeconomic
      status among these Latino populations: Cuban Americans have higher levels of
      education and family income than Mexican-Americans and Puerto Ricans; mainland
      Puerto Rican children have the highest proportion of households led by a single
      mother. Our review of past research documents differences in asthma outcomes
      among Latino children and identifies the possible genetic, environmental, and
      health care factors associated with these differences. Based on this review, we
      propose research studies designed to differentiate between mutable and immutable
      risk and prognostic factors. We also propose that the sociocultural milieus of
      Latino subgroups of different ethnic and geographic origin are associated with
      varying patterns of risk factors that in turn lead to different morbidity
      patterns. Our analysis provides a blue-print for future research, policy
      development, and the evaluation of multifactorial interventions involving the
      collaboration of multiple social sectors, such as health care, public health,
      education, and public and private agencies.

PMID- 10063394
TI  - Latino children's health and the family-community health promotion model.
AB  - A majority of Latino children in the US live in poverty. However, unlike other
      poor children, Latino children do not seem to have a consistent association
      between poverty and poor health. Instead, many poor Latino children have
      unexpectedly good health outcomes. This has been labeled an epidemiologic
      paradox. This paper proposes a new model of health, the family-community health
      promotion model, to account for this paradox. The family-community health
      promotion model emphasizes the family-community milieu of the child, in contrast
      to traditional models of health. In addition, the family-community model expands
      the outcome measures from physical health to functional health status, and
      underscores the contribution of cultural factors to functional health outcomes.
      In this paper, we applied the family-community health promotion model to four
      health outcomes: low birthweight, infant mortality, chronic and acute illness,
      and perceived health status. The implications of this model for research and
      policy are discussed.

PMID- 10063395
TI  - Placebo medication use in patient care: a survey of medical interns.
AB  - The use of placebo medication, long recognized by clinicians, often has serious
      practical implications, such as patient deception. Past evidence has suggested
      that resident physicians tend to misuse placebo medication. Interns from two
      consecutive years of a residency program were surveyed anonymously to assess
      their knowledge and use of placebos. Of the 74 interns surveyed, 44 (59%) were
      familiar with placebo use in patient care. Fifty percent of these interns
      familiar with placebo use had learned about placebos from another physician. All
      interns who had learned about placebos during their internships had learned from
      another physician, whereas interns who had gained their knowledge of placebos as
      medical students were as likely to have learned from the medical literature as
      they were to have learned from a physician (P = 0.027). Interns aware of placebo
      use were more likely to consider placebo administration for suspected, factitious
      pain (P = 0.022). The present study uncovered no relationship between interns'
      estimations of placebo efficacy and the utility they attributed to placebos in
      assessing a complaint of pain. This suggests that conceptual inconsistencies
      underlie their use of placebos. Interns often learn of placebos as medical
      students and are influenced by physician-mentors. Placebo use in patient care is
      an area of attention for medical educators.

PMID- 10063396
TI  - International travel and vaccinations.
AB  - With the increase in global travel, no disease is beyond the reach of any
      population. Traveling patients should be advised to follow food and water
      precautions and encouraged to receive the recommended immunizations. Travel
      medicine plays a vital role not only in limiting the morbidity of travel-related
      illnesses but also in limiting the spread of diseases. This article addresses the
      common issues related to travel, reviews the care of the immunocompromised
      traveler, and updates the available vaccinations and prophylactic regimens
      available to limit sickness abroad.

PMID- 10063397
TI  - Amebic liver abscess: epidemiology, clinical features, and outcome.
AB  - Amebic liver abscess (ALA) is a serious, but readily treatable form of hepatic
      infection. In order to understand the clinical features of this condition in the
      United States, we reviewed the medical histories of 56 patients with ALA at two
      large San Francisco Hospitals from 1979 to 1994. Patients were divided into the
      following groups based on the presumed manner in which they had acquired ALA:
      those born or raised in the United States, with a history of travel to an endemic
      area (Tr-ALA); those from an endemic area, but living in the United States for
      less than one year (En-ALA); and those neither from nor having traveled to an
      endemic area (N-ALA). We found distinct clinical patterns in patients from
      different epidemiological groups. Patients with Tr-ALA were a decade older than
      those from endemic regions, were more likely to be male, and tended to have an
      insidious onset. Furthermore, compared to patients with En-ALA, those with Tr-ALA
      were more likely to have hepatomegaly (P < 0.0001) and large abscesses (ALA > 10
      cm; P < 0.01). One third of the patients studied had no associated travel history
      or endemic origin as risk factors. Of these, 63% had a condition consistent with
      severe immunosuppression, such as infection with the human immunodeficiency virus
      (HIV), malnourishment with severe hypoalbuminemia, or chronic infection. In
      patients with N-ALA, the presence of a presumed immunosuppressed state increased
      significantly, as compared to patients with endemic or travel risk factors for
      ALA. During the last five years of the study, one third of all patients diagnosed
      with ALA were HIV positive (including 2 with a new diagnosis of AIDS), many of
      whom were discovered to be HIV-infected only after presentation with ALA. We
      conclude that travel to and origin in an endemic area are important risk factors
      for the development of ALA, and patients in these different epidemiological
      groups appear to have distinct clinical features. Further, in the absence of
      recognized risk factors, the development of ALA may suggest an immunocompromised
      host.

PMID- 10063398
TI  - Yersinia pseudotuberculosis bacteremia and splenic abscess in a patient with non
      insulin-dependent diabetes mellitus.

PMID- 10063399
TI  - High-dose praziquantel with cimetidine for refractory neurocysticercosis: a case
      report with clinical and MRI follow-up.

PMID- 10063400
TI  - Diabetic ketoacidosis in pregnancy with a recent normal screening test.

PMID- 10063401
TI  - Parathyroid cyst: an uncommon cause of a palpable neck mass and hypercalcemia.

PMID- 10063402
TI  - Non-cardiogenic pulmonary oedema in vascular surgery.
AB  - Non-cardiogenic pulmonary oedema, an early manifestation of the adult respiratory
      disease syndrome, is a serious complication following major vascular surgery.
      Hypovolaemia, ischaemia-reperfusion injury, massive blood transfusion, transient
      sepsis and transient endotoxaemia are insults responsible for initiating the
      process in vascular surgical patients. Free radicals, cytokines and humoral
      factors released secondary to the above insults activate neutrophils and
      facilitate their interaction with the endothelium. Activated neutrophils
      marginate through the endothelium where they are responsible for tissue injury by
      the release of free-radicals and proteases. The lungs are a large reservoir of
      neutrophils and bear a significant part of the injury. Conventional therapy
      includes treating the underlying condition and providing respiratory support. A
      better understanding of the pathophysiology of this process has led to new
      experimental treatment options. Novel therapeutic interventions have included the
      use of compounds to scavenge free radicals, anti-cytokine antibodies,
      extracorporeal lung support, nitric oxide and artificial surfactant therapy. The
      multifactorial nature of this process makes it unlikely that a single "magic
      bullet" will solve this problem. It is more likely that a combination of
      preventative, prophylactic and therapeutic modalities may reduce the mortality of
      this condition.

PMID- 10063403
TI  - The endovascular management of blue finger syndrome.
AB  - OBJECTIVES: To review our experience of the endovascular management of upper limb
      embolisation secondary to an ipsilateral proximal arterial lesion. DESIGN: A
      retrospective study. MATERIALS AND METHODS: Over 3 years, 17 patients presented
      with blue fingers secondary to an ipsilateral proximal vascular lesion. These
      have been managed using transluminal angioplasty (14) and arterial stenting
      (five), combined with embolectomy (two) and anticoagulation (three)/anti-platelet
      therapy (14). RESULTS: All the patients were treated successfully. There have
      been no further symptomatic embolic episodes originating from any of the treated
      lesions, and no surgical amputations. Complications were associated with the use
      of brachial arteriotomy for vascular access. CONCLUSIONS: Endovascular techniques
      are safe and effective in the management of upper limb embolic phenomena
      associated with an ipsilateral proximal focal vascular lesion.

PMID- 10063404
TI  - Venous ulceration and continuous flow in the long saphenous vein.
AB  - OBJECTIVE: To determine the clinical significance of continuous flow in the long
      saphenous vein in limbs with venous ulceration. DESIGN: Retrospective review.
      PATIENTS AND METHODS: Review of 1608 consecutive limbs undergoing colour duplex
      scanning for venous disease over a 43 month period. RESULTS: Continuous flow in
      the long saphenous vein is seen in 8% of limbs with venous ulceration and in 37%
      of limbs with deep venous obstruction. Sixty-six per cent of ulcerated limbs with
      continuous flow in the long saphenous vein had deep venous obstruction, 27% had
      deep venous reflux with cellulitis and 7% had lymphoedema in addition to venous
      ulceration. CONCLUSION: Continuous flow in the long saphenous vein in patients
      with venous ulceration should alert the clinician to the possibility of deep
      venous obstruction. Such limbs should be treated by compression bandaging with
      extreme caution.

PMID- 10063405
TI  - Does soluble intercellular adhesion molecule-1 (ICAM-1) affect neutrophil
      activation and adhesion following ischaemia-reperfusion?
AB  - OBJECTIVES: To examine the effect of reperfusion plasma and sICAM-1 on neutrophil
      integrin expression and neutrophil adhesion to determine if sICAM-1 has a
      potential role in the regulation of neutrophil adhesion. MATERIALS: Twenty-seven
      patients, 17 men and 10 women undergoing femorodistal surgery. Blood was taken
      preoperatively and from the femoral vein following the release of the cross
      clamp. Neutrophils were obtained from five volunteers and incubated with
      phosphate buffered saline (PBS), preoperative plasma or reperfusion plasma with
      and without sICAM-1. Neutrophil expression of CD11b and adhesion were measured.
      MAIN RESULTS: Neutrophil CD11b expression did not change following incubation in
      the three media. Neutrophil adhesion increased significantly following exposure
      to reperfusion plasma compared to PBS or preoperative plasma (45.5 adhesion vs.
      12.75%, p < 0.01 Mann-Whitney U-test). Soluble ICAM-1 decreased CD11b expression
      and adhesion in neutrophils exposed to reperfusion plasma only (CD11b expression
      fell from 15.9 to 3.4 mcf, p < 0.01 Mann-Whitney U-test and adhesion fell to
      11.6% cells adhered, p < 0.01). CONCLUSION: An increase in CD11b expression is
      not required for an increase in neutrophil adhesion. The change in neutrophil
      adhesion produced by reperfusion plasma can be blocked by sICAM-1. Soluble ICAM-1
      may have a physiological role in the regulation of neutrophil adhesion.

PMID- 10063406
TI  - Infrainguinal revascularisation in the era of vein-graft surveillance--do
      clinical factors influence long-term outcome?
AB  - OBJECTIVES: To investigate the variables affecting the long-term outcome of
      infrainguinal vein bypass grafts that have undergone postoperative surveillance.
      DESIGN: A retrospective analysis. PATIENTS AND METHODS: Details of 299
      consecutive infrainguinal vein grafts performed in 275 patients from a single
      university hospital were collected and analysed. All grafts underwent
      postoperative duplex surveillance. Factors affecting patency, limb salvage and
      survival rates were examined. These factors were gender, diabetes, hypertension,
      aspirin, warfarin, ischaemic heart disease, run-off, graft type, early
      thrombectomy, level of anastomoses and indication for surgery. RESULTS: The 6
      year primary, primary assisted and secondary patency rates were 23, 47, and 57%,
      respectively. Six-year limb salvage and patient survival were 68 and 45%,
      respectively. Primary patency was adversely influenced by the use of composite
      vein grafts. Early thrombectomy was the only factor that significantly influenced
      secondary patency. Limb salvage was worse in diabetic limbs, limbs with poor run
      off and in grafts that required early thrombectomy. Postoperative survival was
      better in males, claudicants and in patients who took aspirin. CONCLUSIONS:
      Although co-morbid factors did not influence graft patency rates, diabetes did
      adversely effect limb salvage. This study, like others before it, confirms that
      aspirin significantly reduces long-term mortality in patients undergoing
      infrainguinal revascularisation.

PMID- 10063407
TI  - Ruptured abdominal aortic aneurysms: selecting patients for surgery.
AB  - OBJECTIVES: Mortality from ruptured abdominal aortic aneurysm (RAAA) remains
      high. Despite this, withholding surgery on poor-prognosis patients with RAAA may
      create a difficult dilemma for the surgeon. Hardman et al. identified five
      independent, preoperative risk factors associated with mortality and proposed a
      model for preoperative patient selection. The aim of this study was to test the
      validity of the same model in an independent series of RAAA patients. METHODS: A
      consecutive series of patients undergoing surgery for RAAA was analysed
      retrospectively by case-note review. Thirty-day operative mortality and the
      presence of the five risk factors: age (> 76 years), creatinine (Cr) (> 190
      mumol/l), haemoglobin (Hb) (< 9 g/dl), loss of consciousness and
      electrocardiographic (ECG) evidence of ischaemia were recorded for each patient.
      RESULTS: Complete data sets existed for 69 patients (mean age: 73 years, range:
      38-86 years, male to female ratio: 6:1). Operative mortality was 43%. The
      cumulative effect of 0, 1 and 2 risk factors on mortality was 18%, 28% and 48%,
      respectively. All patients with three or more risk factors died (eight patients).
      CONCLUSIONS: These results lend support to the validity of the model. The
      potential to avoid surgery in patients with little or no chance of survival would
      spare unnecessary suffering, reduce operative mortality and enhance use of scarce
      resources.

PMID- 10063408
TI  - Incisional hernias in patients with aortic aneurysmal disease: the importance of
      suture technique.
AB  - OBJECTIVE: To study the rate of incisional hernia at 12 months in patients
      undergoing abdominal aortic aneurysm repair compared with others undergoing other
      surgery through midline incisions. METHODS: A prospective study of 1023 patients,
      85 of these with aneurysmal disease. Wounds were continuously closed and the
      suture technique was monitored by the suture length to wound length ratio.
      RESULTS: Wound incisions were longer and operations lasted longer in aneurysm
      patients than in others. Incisional hernia was less common if closure was with a
      suture length to wound length ratio of at least four. Wounds were closed with a
      ratio of four or more in 39% (33 of 85) of aneurysm patients and in 59% (546 of
      923) of others (p < 0.01). In aneurysm patients no wound dehiscence was recorded,
      the rate of wound infection was low and incisional hernia occurred in the same
      amount as in others. CONCLUSIONS: It is concluded that the rate of incisional
      hernia is similar in patients with abdominal aortic aneurysmal disease and
      others. Wounds are closed with a less meticulous suture technique in aneurysm
      patients.

PMID- 10063409
TI  - Arterial damage induced by cryopreservation is irreversible following organ
      culture.
AB  - OBJECTIVES: The aim of the present study was to investigate the changes which
      occur to the arterial wall following cryopreservation and thawing and to
      determine whether these changes are reversible after a week of culture in an
      organ bath. MATERIALS AND METHODS: Rat iliac arterial segments were
      cryopreserved. Once thawed, the arterial segments were cultured for a period of
      0, 1, 2, 4 or 7 days. Freshly isolated rat iliac vessels cultured for 7 days
      served as the control group. Evaluation was made of ultrastructural changes, the
      expression of metalloproteinase activity (MMP-1, MMP-3 and MMP-9) and the
      apoptotic state of cells. RESULTS: The freezing-thawing process induced damage to
      the arterial segments compared to fresh control vessels. After 1 week of culture,
      arteries showed a high degree of tissue degeneration. Only a few individual
      endothelial cells remained on the luminal surface. There was a gradual increase
      in the proportion of apoptotic cells. The sequential expression of MMP-1 during
      the first 2 days and subsequent expression of MMP-3 and MMP-9 were of most
      significance. CONCLUSIONS: Cryopreservation induced damage to the vessels which
      could not be reversed by organ culture. The changes observed in the expression of
      metalloproteinases may be indicative of the degenerative process which occurs in
      the extracellular matrix.

PMID- 10063410
TI  - Age-related outcome for peripheral thrombolysis.
AB  - OBJECTIVES: To investigate the age-related outcome of peripheral thrombolysis and
      determine for which patient group this treatment is worthwhile. DESIGN AND
      METHODS: A combined retrospective and prospective analysis of consecutive
      patients undergoing thrombolysis for acute lower-limb ischaemia was made with
      respect to age-related outcome and other risk factors. RESULTS: One hundred and
      two patients underwent thrombolysis for acute limb ischaemia. In the under 60 age
      group there was a 40% amputation rate. Seventy-three per cent of this group
      smoked. In the over 80 age group, the amputation rate was 15% and only 8% were
      smokers. CONCLUSION: Advancing age is not an adverse risk factor for thrombolysis
      which appears to be safe and effective in this patient group. There is a high
      incidence of smoking in the younger age group (< 60 years), in whom failed
      thrombolysis frequently leads to amputation.

PMID- 10063411
TI  - Is there a relationship between abdominal aortic aneurysms and alpha1-antitrypsin
      deficiency (PiZ)?
AB  - OBJECTIVE: To determine if the frequency of alpha 1AT deficiency (PiZ) is
      increased in patients with abdominal aortic aneurysm (AAA), and, to investigate
      whether aneurysmal stiffness and other clinical characteristics differ in AAA
      patients with and without alpha 1AT deficiency. METHODS: We identified alpha 1AT
      deficient individuals by a monoclonal-antibody ELISA technique, in 102
      consecutive patients with AAA. Positive ELISA samples were further phenotyped by
      isoelectric focusing to differentiate between the heterozygosity (PiZ) and
      homozygosity (PiZZ) state. Aneurysmal diameter and stiffness was measured using
      echotracking sonography and blood pressure measurements. RESULTS: The frequency
      of heterozygous alpha 1AT deficiency (PiZ) in patients with AAA was similar to
      that in the general population (6.8% and 4.7%, respectively, p > 0.3). The
      frequency of popliteal and femoral aneurysm was similar in male PiZ-carriers and
      non-carriers with AAA, as were age at diagnosis of AAA, aneurysmal diameter,
      aneurysmal stiffness, and presence of factors that may be associated with AAA
      (i.e. smoking, hypertension, diabetes mellitus, and family history of AAA).
      Occurrence of ischaemic heart disease was more frequent in male non-PiZ-carriers
      than in male PiZ-carriers with AAA (p = 0.03). CONCLUSIONS: The frequency of
      alpha 1AT deficiency (PiZ) was not increased in our series of patients with AAA
      and patients in whom the two disorders coexisted did not appear to have different
      clinical characteristics except for the lower occurrence of ischaemic heart
      disease among the PiZ-carriers.

PMID- 10063412
TI  - Perceived health in a randomised trial of treatment for chronic venous
      ulceration.
AB  - STUDY OBJECTIVE: To observe changes in perceived health in patients during a
      clinical trial of treatments for venous leg ulceration. DESIGN: Randomised
      prospective factorial trial in patients with venous ulceration. Each patient
      randomised to a bandage, dressing and a drug. Perceived health assessed at entry
      and after 24 weeks. SETTING: Outpatient departments and patient's home. PATIENTS:
      Two hundred patients presenting to two vascular services in Falkirk and Edinburgh
      with chronic (duration > 2 months) non-healing venous ulceration. STATISTICAL
      ANALYSIS AND MAIN RESULTS: Analysis using the Nottingham Health Profile revealed
      that after 24 weeks there were significant improvements in all subscores (p <
      0.01) with the exception of social isolation (p = 0.081). Patients with healed
      ulceration had improved in energy, pain, emotion, sleep and mobility compared
      with those whose ulceration failed to heal (p < 0.05). Patients randomised to
      four layer bandaging had significantly better energy (diff = 7.9, 95% CI 0.2,
      15.6, p = 0.04) and mobility (diff = 4.5, 95% CI 0.0, 9.0, p = 0.046). This
      difference could be explained largely by the improved healing of patients
      randomised to this bandage system (67/97 vs. 50/103, OR = 2.37, 95% CI 1.31,
      4.27). CONCLUSIONS: Improvements in perceived health were significantly greater
      in patients whose ulcers had completely healed. Methods of treatment which offer
      improved healing for patients with venous leg ulceration are likely to improve
      patients' perceived health status.

PMID- 10063413
TI  - Repair of ruptured thoracoabdominal aortic aneurysm is worthwhile in selected
      cases.
AB  - INTRODUCTION: The risks and benefits of operating on patients with ruptured
      thoracoabdominal aortic aneurysm (TAAA) have not been defined. The aim of the
      present study is to report this unit's experience with operations performed for
      ruptured TAAA over a 10-year period. METHODS: Interrogation of a prospectively
      gathered computerised database. PATIENTS: Between 1 January 1983 and 30 June
      1996, 188 consecutive patients with TAAA were operated on, of whom 23 (12%) were
      operated for rupture. RESULTS: There were nine survivors (40%). Patients whose
      preoperative systolic blood pressure remained above 100 mmHg were significantly
      more likely to survive (4/8 vs. 13/15, p = 0.03 by Fisher's exact test). Survival
      was also related to Crawford type: type I (two of three survived); II (none of
      six); III (two of six); and IV (five of eight). All non-type II, non-shocked
      patients survived operation. Survivors spent a median of 28 (range 10-66)
      postoperative days in hospital, of which a median of 6 (range 2-24) days were
      spent in the intensive care unit. Survivor morbidity comprised prolonged
      ventilation (> 5 days) (n = 3); tracheostomy (n = 1); and temporary
      haemofiltration (n = 2). No survivor developed paraplegia or required permanent
      dialysis. CONCLUSIONS: Patients in shock with a Crawford type II aneurysm have
      such a poor prognosis that intervention has to be questioned except in the most
      favourable of circumstances. However, patients with types I, III and IV who are
      not shocked on presentation can be salvaged and, where possible, should be
      transferred to a unit where appropriate expertise and facilities are available.

PMID- 10063414
TI  - Association between age and survival following major amputation. The Scottish
      Vascular Audit Group.
AB  - OBJECTIVES: To determine whether age is associated with survival following major
      amputation and whether this association is independent or simply reflects
      selection bias in amputation level. DESIGN AND MATERIALS: Computer linkage of
      routine discharge and death data on the 2759 patients undergoing major amputation
      in Scotland between 1989 and 1993 for peripheral arterial disease. METHODS: Cox's
      proportional hazards model and multivariate logistic regression analysis using
      death as the outcome variable and age, sex, urgency, amputation level and recent
      arterial reconstructive surgery as predictor variables. RESULTS: Proximal
      amputation was more common in older patients. Survival was associated with both
      age (p < 0.001) and amputation level (p < 0.001). Age was an independent
      predictor of death at 30 days (p < 0.0001), 6 months (p < 0.001), 12 months (p <
      0.0001) and 2 years (p < 0.0001) postoperation. CONCLUSIONS: Survival following
      amputation was poor, with only half the patients alive at 2 years. Above-knee
      amputation was associated with poorer survival, presumably due to the presence of
      more severe and widespread disease, and was undertaken more commonly in older
      patients. However, age remained a predictor of survival after adjustment for
      amputation level. Higher early mortality suggest that a worse prognosis in
      elderly patients cannot be attributed wholly to actuarial considerations.

PMID- 10063415
TI  - Temporary surgical arterial closure technique with tourniquet allows transfemoral
      endovascular repair of aortic aneurysm in local anaesthesia.

PMID- 10063416
TI  - Coronary stent embolisation: when do we intervene?

PMID- 10063417
TI  - Thoracoscopic sympathectomy for ischaemic lesions related to bleomycin therapy
      for acquired immune deficiency syndrome-related Kaposi's sarcoma.

PMID- 10063418
TI  - Angiolymphoid hyperplasia presenting as a radial artery aneurysm.

PMID- 10063420
TI  - American Society for Neurochemistry 30th annual meeting. New Orleans, Louisiana,
      USA. March 14-17, 1999. Abstracts.

PMID- 10063419
TI  - A popliteal false aneurysm caused by an avulsion fracture of the femur: a case
      presenting with deep venous thrombosis.

PMID- 10063421
TI  - 4th International Symposium on High-dose Chemotherapy and Stem Cell
      Transplantation in Solid Tumors. Berlin, Germany, 18-19 April 1998. Abstracts.

PMID- 10063422
TI  - 21st Annual San Antonio Breast Cancer Symposium. December 12-15, 1998. Abstracts.

PMID- 10063424
TI  - 15th International Congress on Thrombosis. Antalya, Turkey, October 16-21, 1998.
      Abstracts.

PMID- 10063423
TI  - XI Congress of the European College of Neuropsychopharmacology. Paris, France,
      October 31-November 4, 1998. Abstracts.

PMID- 10063425
TI  - 73rd Annual meeting of the Canadian Dermatology Association. Toronto, Ontario,
      Canada. June 30-July 4, 1998. Abstracts.

PMID- 10063426
TI  - 7th Annual meeting of the Israel Society for Neurosciences. Eilat, Israel,
      December 6-8, 1998. Abstracts.

PMID- 10063427
TI  - Three-dimensional echocardiography: the future today!
AB  - Three-dimensional echocardiography depicts the heart and its structures in their
      realistic forms. This capability decreases variability both in the quality and
      the interpretation of complex pathology, among investigators. Therefore, it is
      likely that the method will become the standard echocardiography examination in
      the future. The availability and versatility in use of the volumetric data set
      allows to retrieve an infinite number of cardiac cross-sections which allow more
      accurate and reproducible measurements of valve areas, masses and cavity volumes
      by obviating geometric assumptions. In the future new physiologic parameters will
      provide additional information and will allow to address new clinical questions.

PMID- 10063428
TI  - Mild to moderate hyperhomocysteinaemia in cardiovascular disease.
AB  - Elevated serum levels of homocysteine, a sulphur-containing amino acid, are
      increasingly recognized as an independent risk factor for atherosclerotic and
      thrombotic vascular disease. Presence of a thermolabile variant of
      methylenetetrahydrofolatereductase and an inadequate folate status are the most
      common causes of hyperhomocysteinaemia. Homocysteine damages the vessel wall
      mainly through generation of oxygen radicals and creates a prothrombotic
      environment. In the majority of cases, normalization of homocysteine levels can
      be achieved with administration of vitamins of the B-group. The effect of this
      treatment on cardiovascular outcome, however, remains undefined.

PMID- 10063429
TI  - Relationship between serum C3 levels and traditional risk factors for myocardial
      infarction.
AB  - OBJECTIVE: Serum C3, a complement component produced by macrophages, the liver
      and the adipose tissue, is associated with the risk of myocardial infarction in
      men. This study was performed to ascertain the relationships between serum C3 and
      traditional risk factors in an unselected population sample. METHODS AND RESULTS:
      A random population of 1,068 subjects (537 men and 531 women, 23 to 90 years old)
      was examined for risk factor assessment. Serum C3 was measured by nephelometry.
      C3 was independently associated with body mass index (P < 0.0005, especially in
      women), LDL-cholesterol (P = 0.0014 in men and 0.0215 in women), systolic blood
      pressure (P < 0.05) and, in women, with triglycerides (P = 0.0133) and blood
      glucose (P = 0.0383), as assessed by multivariate analysis (multiple linear
      regression). The overall R2 were 0.07 and 0.21 for men and women, respectively.
      Women over 50 years of age had significantly higher C3 levels, LDL-cholesterol
      and body mass index than younger women. The correlation of C3 with LDL
      cholesterol was present after the age of 40 in men, and 2 decades later in women.
      CONCLUSIONS: These data show that serum C3 correlates with a cluster of
      conventional risk factors for myocardial infarction resembling insulin
      resistance. Such correlations may be either independent of, or mediated by the
      development of coronary atherosclerosis.

PMID- 10063430
TI  - The effect of electroconvulsive therapy on QT dispersion.
AB  - Electroconvulsive therapy (ECT) is used frequently in psychiatric practice and
      various electrocardiographic (ECG) changes have been described during ECT. QT
      dispersion (defined as maximal QT interval minus minimal QT interval) as assessed
      on the surface electrocardiogram has been demonstrated to reflect regional
      inhomogeneity of ventricular repolarization. The aim of this study is to examine
      the effect of electroconvulsive therapy on QT dispersion. We studied 27 patients
      (age range 24-42 y, mean age 34 y, 11 men) without heart disease who were treated
      with ECT. Structural heart disease was eliminated with routine clinical
      examination and laboratory tests, echocardiography, and exercise treadmill test.
      QT interval and corrected QT (QTc) dispersion was measured on a 12-lead ECG
      before and just after ECT. QTc dispersion increased from 28.9 +/- 7.4 ms at
      baseline to 81.4 +/- 12.8 ms after the procedure (P < 0.0001). This result
      demonstrated that QTc dispersion increased significantly during ECT. This finding
      may explain that increased inhomogeneity of ventricular repolarization is
      associated with enhanced vulnerability to arrhythmias during ECT.

PMID- 10063431
TI  - Nutritional habits and serum lipid levels in a low-fat intake Chinese population
      sample.
AB  - The dietary intake of macronutrients and of specific minerals and vitamins was
      measured in a low-fat intake adult population living in a rural area in
      northwestern China. The total intake of fat amounted to +/- 12% of total energy.
      The P/S ratio was 2.5 and the U/S ratio 3.8. Carbohydrates provide about 75% of
      total energy. The mean total serum cholesterol was 148 mg/dl in men and 163 mg/dl
      in women. The mean HDL-cholesterol level was 38.6 mg/dl in men and 39.4 mg/dl in
      women, confirming the absence of a significant sex difference in HDL-cholesterol
      in low-fat consuming populations. Triglyceride levels were similar to those of
      Western populations. For both sexes taken together a positive correlation was
      found between the serum cholesterol level and saturated fat intake (p < 0.001)
      and a negative correlation with the P/S ratio (p < 0.05). Calcium intake was low:
      346 mg/d in men and 245 mg/d in women.

PMID- 10063432
TI  - Creating yourself a disease.

PMID- 10063433
TI  - Primary pulmonary hypertension in a patient with HIV infection.
AB  - Several case-reports and small series suggest a causal relationship between human
      immunodeficiency virus (HIV) infection and pulmonary hypertension. We report on a
      HIV seropositive man with a high and stable CD4 lymphocyte count (+/- 600/mm3)
      who developed severe pulmonary hypertension, not attributable to other known
      causes. This case report underscores the fact that the degree of
      immunosuppression secondary to the HIV-infection seems to be of little relevance
      in the pathophysiology of the syndrome. HIV-infected patients with dyspnoea, not
      related to pulmonary infection, with exercise intolerance, syncope or precordial
      pain should receive an electrocardiogram and echocardiographic assessment. The
      exact pathogenetic mechanism of this rapidly progressive disease and whether anti
      viral therapy should be promoted is still under investigation.

PMID- 10063434
TI  - Red blood cell substitutes: evolution of approaches to demonstrating efficacy.
AB  - There has been a striking advancement in our understanding of red cell
      substitutes over the past decade. Throughout this period, regulatory oversight
      influenced many aspects of product development. The approach to demonstrating
      efficacy was an important example. I will review some events of the decade so
      that we may consider the question, "If we had it to do over again, could we do
      any better?" At the start of the decade, there were sufficient data on the
      mechanism of hemoglobin-induced renal toxicity to reach consensus among
      investigators that the content of alpha beta-dimers in any hemoglobin product
      must be strictly limited. An array of additional, unexpected reactions were seen
      in early clinical studies, reactions that led to several conclusions: hemoglobin
      is a pharmacologically active material; more basic studies are needed; and it
      would all be so much easier if communications between investigators were open and
      unhindered. Meaningful studies of efficacy could not be approached until the
      safety issues had been solved or until the community was convinced that they were
      not serious. The initial approach was based on the meager experience gained with
      previous products, e.g., Fluosol. That experience led to policies which required
      that, for example, if the product was to be used as a red cell substitute, it
      must be compared with red cells, and if it was to be used as an oxygen carrier,
      it must be shown to support organ function. Endpoints of clinical trials were
      based on delivery of a clear clinical benefit to the patient--surrogate endpoints
      could be used only if their relationship to clinical benefit had been
      demonstrated.

PMID- 10063435
TI  - Physiologic responses of cross-linked hemoglobin in endotoxin-treated rats.
AB  - Purified human cross-linked hemoglobin (alpha alpha Hb) as well as recombinant
      human hemoglobin is undergoing clinical trials in the setting of acute blood loss
      and perioperative hemodilution. We have previously demonstrated that in rabbits
      with circulating plasma Hb, such as alpha alpha Hb, infusion of endotoxin (LPS)
      impairs myocardial contractility which results in hypotension, tissue
      hypoperfusion and increased mortality. The untoward cardiovascular effects
      occurring after the combined infusion of LPS and alpha alpha Hb in this model are
      similar to those reported for other agents that inhibit nitric oxide (NO)
      availability. To determine if the deleterious effects of alpha alpha Hb and LPS
      were species specific, we performed similar studies in rats. Anesthetized Sprague
      Dawley rats received LPS (4 mg/kg or 40 mg/kg) alone or in combination with alpha
      alpha Hb (0.7 g/kg). Mean arterial blood pressures (MAP) increased in the group
      that received alpha alpha Hb alone (105 +/- 8 to 120 +/- 7 mm Hg, p = 0.2) and a
      decrease was noted in the groups that received low dose LPS (4 mg/kg, p = 0.5)
      and high dose LPS (40 mg/kg, p = 0.016). MAP in rats treated with the LPS at
      either dose combined with alpha alpha Hb remained unchanged. Levels of urine
      nitrite, which was measured as a surrogate marker for plasma NO, were
      significantly decreased at 2 hr in groups that received the combination of alpha
      alpha Hb and LPS at 4 mg/kg (p = 0.022) and 40 mg/kg (p = 0.003). No significant
      decrease was observed in animals treated only with alpha alpha Hb (p = 0.21) or
      LPS (4 mg/kg; p = 0.78 and 40 mg/kg; p = 0.65). Survival was evaluated during 72
      hr in animals that were infused with high dose LPS (40 mg/kg) alone or in
      combination with alpha alpha Hb and then allowed to recover. The survival of rats
      treated with LPS alone or the combination was 29% at the end of 24 hr and was
      100% for rats receiving only alpha alpha Hb. The data suggest that the toxicity
      of alpha alpha Hb appears to be a species specific phenomenon.

PMID- 10063436
TI  - Complement-mediated acute effects of liposome-encapsulated hemoglobin.
AB  - Recent studies on liposome-encapsulated hemoglobin (LEH) have indicated that this
      potential blood substitute can activate the complement (C) system of rats, pigs
      and man. The reaction can involve both the classical and the alternative
      pathways, and is mediated, in part, by the binding of natural anti-lipid
      antibodies to the lipid membrane of liposomes. The significance of these
      discoveries lies in the fact that C activation appears to be the primary cause of
      the acute physiological, hematological and laboratory changes that have been
      observed previously in rats and pigs following the administration of LEH or
      liposomes, which changes include pulmonary vasoconstriction with decreased
      cardiac output. In light of the proposed use of LEH as an emergency blood
      substitute, the latter impairment of cardiopulmonary function may warrant
      particular circumspection as it could aggravate the clinical state of trauma
      patients who are prone to develop respiratory distress partly as a consequence of
      C activation by the injury. Our studies on rats and pigs suggest that the above
      acute side effects of LEH, including the cardiopulmonary distress, can be
      efficiently inhibited with soluble complement receptor type I, a specific
      inhibitor of C activation.

PMID- 10063437
TI  - Blood program and the possibility of applying red cell substitutes in Indonesia.

PMID- 10063438
TI  - The effects of stroma-free and dextran-conjugated hemoglobin on hemodynamics and
      carotid blood flow in hemorrhaged guinea pigs.
AB  - Hemoglobin solutions are potential resuscitative fluids with volume expanding and
      oxygen delivery abilities developed to reduce the use of blood transfusion. Most
      hemoglobin solutions in clinical trials increase transiently arterial pressure by
      inhibiting nitric oxide-dependent vasodilation. Our objective was to compare the
      effects on central hemodynamics and carotid blood flow of two hemoglobin
      solutions after resuscitation from hemorrhage in anesthetized guinea pigs. After
      anesthesia and instrumentation, severe hemorrhage was induced by withdrawing 50%
      of the blood volume. Resuscitation was performed after 15 min of hypovolemia with
      5% albumin, stroma-free hemoglobin, or hemoglobin conjugated to dextran
      benzenetetracarboxylate (Dex-BTC-Hb). The mean arterial pressure (MAP), carotid
      blood flow (CBF), vascular resistance index and heart rate (HR) were monitored
      for 3 hours after resuscitation. After hemorrhage, MAP and CBF dropped to 57.6 +/
      4.4% and 58.9 +/- 3.7% of control values respectively. Albumin failed to
      maintain hemodynamics in the decompensatory phase of shock. Both hemoglobin
      solutions gave rise to a transient increase in MAP (35%); stroma-free hemoglobin
      increased the CBF (150%) and resistance index (24%) whereas Dex-BTC-Hb had no
      effect on CBF and vascular resistances. None of the solutions affected the HR.
      Modified hemoglobin has attenuated effects on CBF and resistance index compared
      to stroma-free hemoglobin. This may be due to a balance between the stimulation
      of nitric oxide synthesis by shear-stress and the inhibition of vasodilation by
      nitric oxide trapping.

PMID- 10063439
TI  - Release and retention of biomolecules in collagen deposited on orthopedic
      biomaterials.
AB  - Delivery of osteotropic biomolecules directly to the bone-implant interface can
      alter initial interactions between tissue and biomaterial. To this end, type I
      collagen coatings containing a model biomolecule, lysozyme, were deposited on Co
      Cr-Mo and Ti-6Al-4V. Two deposition methods were examined. In the first, lysozyme
      was deposited concurrently with collagen, while in the second, protein was
      impregnated into previously deposited collagen coatings. The amount of collagen
      and the amount of lysozyme loaded into collagen were varied to provide different
      amounts of weakly and strongly bound protein. Release and retention of lysozyme
      were monitored over a 7 d period of incubation in physiological saline. For both
      methods, larger amounts of collagen in the coatings allowed incorporation of more
      lysozyme. Additionally, loading collagen coatings with greater amounts of
      lysozyme resulted in release of more protein. During the first 24-96 h of
      incubation, loosely bound protein was eluted, resulting in release of 2
      micrograms to 55 mg (5-75% of the amount available) of enzymatically active
      lysozyme. This left 25-95% of the protein bound to the collagen-coated
      biomaterials and, thus, available for later release during degradation of the
      collagen.

PMID- 10063440
TI  - Induction of superficial bladder tumors in the female Fischer 344 rats with AY-27
      tumor cells for the study of diffusion and localization of hemoglobin derived
      components (hematoporphyrin derivative) in view of photochemotherapy.
AB  - Photochemotherapy (PCT) consists in administration of a photosensitizer and
      subsequent irradiation of the tumor with visible light. Routinely, the
      photosensitizer is given intravenously (i.v.), but the major drawback of this
      procedure is the resulting skin photosensitivity. The goal of our study is to
      examine whether intravesical (i.b.) instillation of the photosensitizer for PDT
      of bladder cancer might be feasible in order to target the tumors and to avoid
      the photosensitization phenomenon. After first studying the biodistribution of
      hematoporphyrin derivative (HpD) in vivo in the rat bladder, two and four hours
      after intravesical administration, by fluorescence microscopy, we compared two
      different methods for the induction of superficial bladder tumors in rats with AY
      27 tumor cell line in order to perform the same study on bladder tumors. The best
      results for the penetration depth of HpD in the normal bladder wall were obtained
      two hours after the bladder instillation where the photosensitizer was detected
      only in the bladder surface (urothelium and small part of the chorion). That's
      why we must choose the most appropriate bladder tumor model in order to obtain
      superficial bladder tumors that mimic the clinical behavior of superficial
      bladder cancer in man. Both techniques used in this study gave a high tumor take
      rate in a short time (> 90%). But we really obtained superficial bladder tumors
      directly attached to the bladder surface with one of the two methods of tumor
      induction consisting in the abrasion of the bladder surface prior to the
      administration of the tumoral cells in the bladder cavity.

PMID- 10063441
TI  - Effect of dental material HEMA monomer on human dental pulp cells.
AB  - The purpose of this study was the cytotoxicity assay of dental material HEMA
      monomer to human dental pulp cell by MTT method and application of the flow
      cytometry to analyze effect of dental material on the cell cycle progression. The
      result of MTT method showed the inhibition of cell growth and 50% inhibitory
      concentration (IC50) of HEMA monomer in human dental pulp cell was 815.19
      micrograms/ml. The result of the flow cytometry showed that there was a
      perturbation on human dental pulp cell cycle progression at the phases of Sand
      G2M with a dose-dependent manner. Biomaterials including dental materials should
      be safety to human bodies. Presently, many methods for testing the cytotoxicity
      of biomaterials were suggested. [1-2] MTT method is one of the cytotoxicity
      assay. It was provided by Monsmnn. [3] MTT is a kind of tetrazolium salt [3-(4,5
      dimethylthiazol-2yi)-2,5-diphenyl tetrazolium bromide]. MTT method is the rapid,
      precision and quantitative colorimetric assay for cytotoxicity. It can be used to
      measure the proliferation, cytotoxicity or activation of living cells and is
      capable of handling large number of samples. Many investigators have used this
      advanced method.[4] Flow cytometry (FCM) analyzes the quantity of DNA bonded with
      dyes in each cell. It can provided the information of the cell cycle progression
      in detail. Currently, flow cytometry has been widely and successfully used in
      various fields of basic science research and clinical medicine. This FCM
      technology also can be used to study the cytotoxicity of dental materials and
      evaluate the biocompatibility of dental materials.[5-6] The contents of the study
      were (1) cytotoxicity assay on dental material HEMA monomer in human dental pulp
      cells by MTT method. (2) application flow cytometry to analyze the effect of
      dental material HEMA monomer on the cell cycle progression of the human dental
      pulp cells.

PMID- 10063442
TI  - The anatomy of a crisis. One perspective.
AB  - In this article, the author analyzes the influx of breast implant class action
      lawsuits in the past decade. He discusses the responses of the medical community
      and the manufacturers as well as the impact the media has had on this issue. The
      author recounts the steps he took in his representation of the defense and
      examines the significance of these lawsuits for the industry and the general
      public.

PMID- 10063443
TI  - Basic medical legal principles.
AB  - A contract exists, either expressed or implied, between the physician and the
      patient. If a duty of care was owed by the physician to the patient and the
      standard of care was violated, resulting in the patients' injury, then the
      damages, injury, or loss the patient suffered can be compensated. This article
      reviews the elements of a medical malpractice claim and the factors that may lead
      to such a claim.

PMID- 10063444
TI  - The wheel of misfortune. Genesis of malpractice claims.
AB  - Unlike other surgical specialists, plastic surgeons attending patients who seek
      aesthetic improvement are not trying to make sick patients well, but rather well
      patients better. This not only places a much heavier burden of responsibility on
      the operating surgeons, but also subjects them to a much broader range of a
      patient's reasons for unhappiness. This article examines various fields of
      plastic surgery in terms of liability and offers advice on how best to reduce the
      frequency of such medical liability claims.

PMID- 10063445
TI  - The insurance carrier's viewpoint. Practicing brinksmanship.
AB  - The author presents a guide to the most common elements of the insurance
      industry. A working familiarity of the provisions of one's policy would prevent
      the frequent quarrels between the insurance carrier and the insured. Thus, the
      author attempts to clear up the misconceptions many physicians have about the
      industry. Finally, he offers a word of advice to physicians when choosing an
      insurance carrier.

PMID- 10063446
TI  - Avoiding malpractice in private practice and the hospital setting.
AB  - An overview of very real considerations for the practicing plastic surgeon with
      regards to potential areas of risk and liability have been presented. As one can
      see, the hospital environment presents many potential sources of liability that
      can involve the attending or consulting plastic surgeon.

PMID- 10063447
TI  - Patient selection criteria.
AB  - Most malpractice claims are based on failures of communication and patient
      selection criteria, not on technical faults. This article examines the
      psychological aspects of plastic surgery and then discusses the role of effective
      communication as a claims prevention technique. The authors delineate general
      characteristics of trouble-prone patient groups so that the surgeon may
      distinguish those patients whose body image and personality characteristics make
      them simply unsuitable for the elective aesthetic surgery that they seek.

PMID- 10063448
TI  - Failure in communication. The common denominator.
AB  - Structural changes in the practice of medicine are placing pressures on
      physicians to alter their relations with patients. Most notable among these
      changes are those brought about by managed care organizations. For legal and
      ethical reasons, communication between the doctor and patient is essential.
      Furthermore, there are certain time periods in which this communication is
      especially important.

PMID- 10063449
TI  - Doctor-patient relationship. The consultation.
AB  - This article deals primarily with the office consultation involving a new
      patient. The consultation lays the groundwork for the physician/patient
      relationship in a number of ways. The authors consider the objective and
      subjective assessments which take place between the doctor and the patient and
      offer advice on how to decide on a course of treatment with the patient.

PMID- 10063450
TI  - The medical record. Informing your patients before they consent.
AB  - In the language of medical liability, no concept has received as much
      misinterpretation as "informed consent." In the last five years, most medical
      liability carriers have experienced a significant increase in claims that allege
      failure to obtain a proper informed consent prior to treatment. The authors
      discuss forensic testing of the medical record and offer recommendations for
      record-keeping. These suggestions, if followed, will help establish the
      reliability of the record as an accurate reflection of the treatment of the
      patient in any given case.

PMID- 10063451
TI  - How to handle the stress of litigation.
AB  - The article describes the psychological repercussions of being sued for
      malpractice. Although most physicians experience at least some emotional
      disruption during the process, they usually cope effectively. Factors that
      contribute to stress vulnerability as well as preventive measures are described.
      The influence of commonly shared personality features and the fact that tort law
      is fault based are explored in order to provide a psychological understanding of
      the litigation experience. General and specific approaches toward coping,
      including the importance of social support during the process, are offered.

PMID- 10063452
TI  - How to select counsel and participate in your own defense. The plaintiff's
      perspective.
AB  - The most important initial step a physician can take in a malpractice case is to
      secure the best possible representation for his or her defense. This article
      enumerates the criteria for obtaining quality representation. Among other points,
      the author cautions the physician to consider the motivation of those who are
      defending him or her and explains how to determine if an attorney has one's best
      interests in mind.

PMID- 10063453
TI  - How to select counsel and participate in your own defense. The defendant's
      perspective.
AB  - The successful defense of a medical malpractice case is a team effort between the
      defendant doctor and his or her attorney. However, the most common complaint
      voiced by physicians is the failure, real or perceived, of the selected attorney
      to keep them involved in the preparation of the case and its progress. To
      ameliorate this situation, the author explains how to participate in one's
      defense in a helpful and meaningful fashion.

PMID- 10063454
TI  - The deposition. The defendant's perspective.
AB  - A positive, well-prepared deposition may be the best defense in a medical
      malpractice suit that ultimately may change the course of a physician's career.
      In this article, the author explains the purpose, format, and overall
      significance of the deposition and offers advice on how best to handle it. The
      author enumerates the steps that the defendant should take before, during, and
      after the deposition.

PMID- 10063455
TI  - The expert witness.
AB  - The worst mistake any attorney or physician involved in a case of medical
      negligence can make is to underestimate the opponent. The expert witness may know
      a lot more about a certain field than the physician, or at least a lot more about
      what the basic standard of care is for a particular case. This article discusses
      the importance of the deposition and delineates four aspects of the deposition
      that are of utmost importance in a medical negligence case.

PMID- 10063456
TI  - Trials, settlements, and arbitration. The plaintiff's perspective.
AB  - From a plaintiff's perspective, a jury trial and verdict are prepared for in
      every case. Experienced trial lawyers know, however, that it is preferable for
      both sides to reach an equitable compromise as to the value of a case, rather
      than risk the unknowns involved in a jury determination of a verdict. There are
      legal elements that require an independent analysis to determine whether a trial,
      settlement, or some form of arbitration is the appropriate strategy for a
      plaintiff to pursue.

PMID- 10063457
TI  - Trials, settlements, and arbitration. The defendant's perspective.
AB  - Knowledge, preparation, and planning can greatly increase a physician's chances
      of success in a medical malpractice trial. In this article, the author presents
      an overview of the many questions that must be addressed in any medical
      negligence case in order to determine the many possible strategies that the
      physician and his or her defense attorney must consider. The author addresses the
      strategies of mediation, arbitration, settlements, and trial.

PMID- 10063458
TI  - Continuing issues. Ultrasound-assisted lipoplasty.
AB  - Ultrasound-assisted lipoplasty (UAL), the newest technological advancement in
      cosmetic surgery, has created significant discussion and controversy over the
      past few years. This article provides the reader with an update on the current
      status and continuing issues associated with UAL. The author discusses the role
      of the Task Force that was created to evaluate this new technology, reviews the
      regulatory issues and clinical studies concerning UAL and describes its benefits
      and limitations.

PMID- 10063459
TI  - The risks of laser surgery.
AB  - The science and art of laser surgery are changing rapidly, secondary to a variety
      of socioeconomic and technological forces. Thus, the risks and complications
      continue to be defined. Frequently, it is difficult to determine if an event is a
      side effect, a complication, or an exaggerated or temporary state that occurs
      prior to the desired outcome. Knowledge of the dynamic development of laser
      induced changes and their outcomes can lead to prompt intervention which can
      prevent and/or minimize untoward results.

PMID- 10063460
TI  - The ethics of managed care financial incentives to limit care. Some thoughts for
      specialists.
AB  - This article supplies an introduction to the structure and purpose of managed
      care financial incentives, with particular attention to those affecting referrals
      to specialists. It then addresses some of the ethical problems attending such
      incentive schemes and discusses the characteristics that make some financial
      incentives preferable to others. An agenda for specialists such as plastic
      surgeons who are often on the "receiving end" of incentive schemes designed to
      limit the use of specialty care is outlined. This proposed agenda encourages
      specialists to participate actively in shaping incentive schemes in ways that
      help keep health care costs down without sacrificing patients' interests in
      obtaining necessary specialty care.

PMID- 10063461
TI  - The genesis of plastic surgeon claims. A review of recurring problems.
AB  - The authors examine several cases in which malpractice claims are the result of
      either poor documentation, lack of preoperative photographs, inadequate informed
      consent, or poor patient-selection criteria. In each case, they discuss what
      errors took place and the end result of the claim. The cases presented in the
      article are intended to help readers avoid potential medical malpractice traps in
      the future and be diligent with office documentation.

PMID- 10063462
TI  - The role of communication in the physician's office.
AB  - The apparent cause of a medical malpractice claim almost always fails to reveal
      the unseen emotional and psychologic factors that triggered the patient's visit
      to an attorney; however, the most common element in an adversarial doctor-patient
      relationship is failed communication. By concentrating on using good listening
      skills, physicians can greatly improve their relationship with their patients.
      Furthermore, communication between the physician and the nurse is vital for
      quality patient care as well as avoidance of medical malpractice.

PMID- 10063463
TI  - Anger as the root cause of malpractice claims.
AB  - The virtually unrelenting stress of practicing medicine in the United States
      today is undoubtedly exerting powerful negative effects on the mood and, by
      implication, the effectiveness of American plastic surgeons. The author points
      out that anger is at the root of malpractice claims and offers physicians advice
      on how to prepare their patients for the realities of plastic surgery. By
      creating an atmosphere of trust and partnership, physicians can relieve their
      patients' anxieties and diffuse their anger.

PMID- 10063464
TI  - Plastic surgery pitfalls.
AB  - As a founding member of the physician-owned insurance carrier The Doctors'
      Company, the author has reviewed many plastic surgery policy claims. In this
      article, he presents an overview of the plastic surgery procedures that produce
      the most severe losses. He then offers suggestions on how to proceed with these
      "medical malpractice favorites." The author discusses potential antitrust traps
      and legal recourse for plastic surgeons.

PMID- 10063465
TI  - Between myth and madness: the premigration dream of leaving among young Somali
      refugees.
AB  - Many young Somali refugees experience long premigration waits and a poorly
      delimited transition period in a succession of countries before reaching their
      final destination. During this difficult passage, a myth dealing with departure
      and exodus is collectively constructed, and it serves as a dynamic, mobilizing
      dream that orients individual strategies. This substitution of "dream travel" for
      real travel during the transition period, especially if it is prolonged, may
      cause Somali youths to lose contact with reality and eventually to slide into
      madness. The authors' approach is based on three assumptions: (a) that
      pastoralism predisposes the Somali to value travel as a way of maturing, (b) that
      age-based peer groups create special migratory dynamics, and (c) that an ethic of
      solidarity involves many people in the adventure of a migrant youth. When trapped
      in an indefinite transition period, young men share khat-chewing sessions during
      which they relate success stories and dreams of leaving. Many grow frustrated
      with the delay, and if their departure plans fall through, the "dream trip" often
      becomes "dream madness." Actual cases illustrate how some young Somali get lost
      in their dreams. A young Somali's vulnerability is heightened when he extricates
      himself from the system of reciprocal obligations or when the liminal stage ends
      with the mourning of the impossible dream. In the universe of madness visited by
      some young Somali migrants, the boundaries between the real and the imaginary are
      poorly marked. The paper is based on fieldwork carried out in the Horn of Africa
      and in Canada, interviews with Somali immigrants and members of the community,
      and clinical psychiatric data collected in Montreal.

PMID- 10063466
TI  - The psychologizing of Chinese healing practices in the United States.
AB  - This paper explores ways in which Chinese healing practices have undergone
      acculturation in the United States since the early 1970s. Reacting to what is
      perceived as biomedicine's focus on the physiological, those who describe
      themselves as favoring a holistic orientation often use the language of "energy
      blockage" to explain illness, whether thought of as "physical," "emotional," or
      "spiritual." Acupuncture in particular has been appropriated as one modality with
      which to "unblock" such conditions, leading to its being used by some
      practitioners in conjunction with more psychotherapeutic approaches which include
      valuing the verbalizing of feelings. Some non-Chinese practitioners in the United
      States, returning to older Chinese texts to develop "an American acupuncture,"
      are reinserting diagnoses eliminated from Traditional Chinese Medicine (TCM) by
      the People's Republic of China as "superstition." The assumption has been that
      many such diagnostic categories refer to psychological or spiritual conditions,
      and therefore may be useful in those American contexts which favor this
      orientation. Among these categories are those drawn from traditions of demonology
      in Chinese medicine. What was once a religious category in China turns
      psychological in the American setting. At the same time, many who use these terms
      have, since the late 1960s, increasingly conflated the psychological and the
      religious, the latter being reframed as "spiritual." Thus, this indigenization of
      Chinese practices is a complex synthesis which can be described as simultaneously
      medical, psychotherapeutic, and religious.

PMID- 10063467
TI  - A Moroccan woman suffering from depression: migration as an attempt to escape
      sorcellerie.

PMID- 10063468
TI  - The 'schizophrenic' and the liminal persona in modern society. Essay review.

PMID- 10063469
TI  - Interpreting schizophrenia: construal or construction? A reply to Robert J.
      Barrett.

PMID- 10063470
TI  - Diagnosis of ventilator-associated pneumonia.
AB  - The diagnosis of ventilator-associated pneumonia (VAP) is problematic despite
      numerous attempts at defining acceptable diagnostic criteria and the optimal
      technique for routine respiratory sampling. Clinical criteria have imperfect
      diagnostic reliability in ventilated patients, but remain crucial for defining
      those patients who may require respiratory sampling. Quantitative clinical
      scoring systems may improve the accuracy of clinical diagnosis in some ventilated
      patients. Review of published studies suggest that fibreoptic bronchoscopic
      techniques have greater diagnostic reliability than qualitative endotracheal
      aspirates, despite inconsistent results when comparing the same techniques in
      different centres. However, the cost and invasive nature of bronchoscopic methods
      precludes their use as first-line techniques in VAP. Non-bronchoscopic, non
      directed techniques are cheaper, safer and more widely available alternatives to
      fibreoptic bronchoscopy techniques and have comparable accuracy. Quantitation of
      respiratory tract cultures is useful in excluding VAP in patients with equivocal
      signs of pneumonia. The diagnostic threshold of bacterial load that defines the
      presence of VAP should vary according to the pre-test probability of pneumonia,
      length of ventilation, antibiotic administration and immunocompetence of the
      patient.

PMID- 10063471
TI  - Evaluation of microbicidal activity of a new disinfectant: Sterilox 2500 against
      Clostridium difficile spores, Helicobacter pylori, vancomycin resistant
      Enterococcus species, Candida albicans and several Mycobacterium species.
AB  - The microbicidal activity of a new disinfectant Sterilox, a super-oxidized water,
      containing a mixture of oxidizing substances, was tested against Clostridium
      difficile spores, Helicobacter pylori, vancomycin resistant Enterococcus species,
      Candida albicans and several Mycobacterium species using membrane filters. All
      tests were performed in duplicate with and without added horse serum at 1% and 5%
      v/v. Distilled water, 0.35% peracetic acid (Nu-Cidex) and 2% glutaraldehyde were
      included as controls. Sterilox: spore suspension (9:1 v/v) achieved log10 kill of
      > 5 with 5% horse serum in 2 min against H. pylori, vancomycin resistant
      Enterococcus species, C. albicans and four atypical Mycobacterium species: M.
      avium, M. chelonei, M. xenopi and M. smegmatis. Sporicidal activity of Sterilox
      against Clostridium difficile was markedly diminished in the presence of 5% horse
      serum. Sterilox may be an effective alternative in endoscopy units, as it is a
      potent microbicidal agent and the manufacturer claims it is not corrosive to
      metal and is nontoxic to biological tissues.

PMID- 10063472
TI  - An assessment of triclosan susceptibility in methicillin-resistant and
      methicillin-sensitive Staphylococcus aureus.
AB  - Triclosan is widely used to reduce skin colonization with staphylococci and is
      incorporated into methicillin-resistant Staphylococcus aureus (MRSA) eradication
      regimes. Using an agar dilution method, the minimum inhibitory concentration
      (MIC) to triclosan was determined for 186 isolates of MRSA and methicillin
      sensitive Staphylococcus aureus (MSSA). Fourteen isolates (7.5%) were detected
      with a MIC > or = 1.0 part per million (ppm). There was no significant difference
      between the incidence of triclosan resistance in strains of MSSA and MRSA. None
      of 16 strains of MRSA which exhibited low-level mupirocin resistance had MIC's >
      or = 1.0 ppm. Increased MIC's of staphylococci to triclosan may contribute to
      treatment failure when used to eradicate staphylococcal carriage. We suggest that
      routine susceptibility testing of staphylococci against triclosan might now be
      indicated.

PMID- 10063473
TI  - Mycobactericidal activity of selected disinfectants using a quantitative
      suspension test.
AB  - In this study, a quantitative suspension test carried out under both clean and
      dirty conditions was used to assess the activity of various instrument and
      environmental disinfectants against the type strain NCTC 946 and an endoscope
      washer disinfector isolate of Mycobacterium chelonae, Mycobacterium fortuitum
      NCTC 10,394, Mycobacterium tuberculosis H37 Rv NCTC 7416 and a clinical isolate
      of Mycobacterium avium-intracellulare (MAI). The disinfectants tested were; a
      chlorine releasing agent, sodium dichloroisocyanurate (NaDCC) at 1000 ppm and
      10,000 ppm av Cl; chlorine dioxide at 1100 ppm av ClO2 (Tristel, MediChem
      International Limited); 70% industrial methylated spirits (IMS); 2% alkaline
      glutaraldehyde (Asep, Galan); 10% succinedialdehyde and formaldehyde mixture
      (Gigasept, Schulke & Mayr); 0.35% peracetic acid (NuCidex, Johnson & Johnson);
      and a peroxygen compound at 1% and 3% (Virkon, Antec International). Results
      showed that the clinical isolate of MAI was much more resistant than M.
      tuberculosis to all the disinfectants, while the type strains of M. chelonae and
      M. fortuitum were far more sensitive. The washer disinfector isolate of M.
      chelonae was extremely resistant to 2% alkaline activated glutaraldehyde and
      appeared to be slightly more resistant than the type strain to Nu-Cidex,
      Gigasept, Virkon and the lower concentration of NaDCC. This study has shown
      peracetic acid (Nu-Cidex), chlorine dioxide (Tristel), alcohol (IMS) and high
      concentrations of a chlorine releasing agent (NaDCC) are rapidly
      mycobactericidal. Glutaraldehyde, although effective, is a slow mycobactericide.
      Gigasept and Virkon are poor mycobactericidal agents and are not therefore
      recommended for instruments or spillage if mycobacteria are likely to be present.

PMID- 10063474
TI  - A Norwegian nosocomial outbreak of methicillin-resistant Staphylococcus aureus
      resistant to fusidic acid and susceptible to other antistaphylococcal agents.
AB  - In Norway, infections caused by methicillin resistant Staphylococcus aureus
      (MRSA) are still uncommon. From December 1993 to January 1997, MRSA was isolated
      from 22 people in Oslo county; 17 patients and five carriers (healthcare
      workers). A cluster of ten people (five patients and five healthcare workers)
      were associated with an outbreak at two hospitals in Oslo. The five patients were
      all admitted to the same intensive care unit (ICU) at Ulleval University Hospital
      between May-July 1995 (they were not transferred from abroad) and treated for
      acute neurological lesions. After surgery, four of them (one died) were
      transferred to another hospital for rehabilitation and training. The presence of
      MRSA was discovered in the patients and the five healthcare workers during the 10
      months June 1995-March 1996. All cluster strains showed an unusual antibiotic
      resistance pattern in vitro, with a relatively low degree of methicillin
      resistance, resistance to fusidic acid, but sensitivity to all other anti
      staphylococcal agents. A clonal spread of this fusidic acid resistant MRSA was
      supported by strain typing using pulsed-field gel electrophoresis (PFGE), which
      showed that all ten cluster strains belonged to one type or its subtype.

PMID- 10063475
TI  - Evaluation of tube coagulase and a fluorogenic substrate for rapid detection of
      methicillin-resistant Staphylococcus aureus from selective enrichment broth in an
      outbreak of EMRSA 15.
AB  - We investigated the use of tube coagulase and a fluorescent substrate, N-t-BOC
      val-pro-arg-7-amido-4-methylcoumarin for the rapid detection of MRSA in selective
      broth enrichment cultures during an outbreak. These methods were compared with
      direct plating of swabs and plating a selective broth enrichment culture using
      200 screening swabs collected from forty patients during the investigation of an
      outbreak of E-MRSA 15. Overall 66 swabs were positive for MRSA following
      subculture of broth enrichment culture. Direct plating detected 25 (38%)
      positives, tube coagulase 37 (56%), and fluorescent substrate 49 (74%)
      respectively, although nine of the 49 turned out to be false reactions. When
      detection from individual patients was analyzed, selective broth subculture
      identified 28 patients colonized with MRSA. Direct plating detected only 12 (43%)
      of these patients. The tube coagulase and fluorescence methods detected MRSA in
      17 (60%) and 19 (68%) patients respectively. The tube coagulase method was found
      to be 100% specific for MRSA suggesting its use as a rapid method for the
      detection of MRSA from selective enrichment broth.

PMID- 10063476
TI  - Isolation and epidemiological study of vancomycin-resistant Enterococcus faecium
      from patients of a haematological unit in Poland.
AB  - Enterococcus faecium has recently emerged as a serious nosocomial pathogen.
      Vancomycin resistant enterococci (VRE) have been isolated in Europe and the USA
      since 1988. This is the first report on isolation of vancomycin resistant E.
      faecium (VREM) strains in Poland, from Haematological Unit patients in the
      Clinical Hospital in Gdansk. In total, 6412 samples were examined between
      December 1996 and October 1997. Five hundred and five isolates of Enterococcus
      spp. were collected. One hundred and one were classified as Enterococcus faecium
      of which 49 were resistant to vancomycin (MIC > 256 mg/L) and teicoplanin (MIC >
      256 mg/L), characteristic of the VanA phenotype. Twenty-nine patients were
      infected or colonized. A PCR-based specific diagnostic assay confirmed the
      phenotype. The multiplex PCR-restriction fragment length polymorphism patterns
      were consistent with VanA-type of vancomycin-resistant E. faecium for all
      isolates examined. These isolates were epidemiologically-related as shown by PCR
      fingerprinting.

PMID- 10063477
TI  - Rapid detection of toxigenic Clostridium difficile from stool samples by a nested
      PCR of toxin B gene.
AB  - Toxigenic Clostridium difficile is the aetiologic agent of most cases of
      antibiotic-associated diarrhoea and pseudomembranous colitis. The present
      standard method for C. difficile diagnosis is a cytotoxicity assay, performed on
      human fibroblast cultures. It is time consuming and requires special facilities.
      A nested-PCR assay detecting toxin B gene within a few hours was designed. One
      hundred and two stool samples were collected during four months. All samples were
      processed for toxin B-PCR, cultured for C. difficile and tested for cytotoxicity.
      This approach achieved 99% concordance with the cytotoxic assay. The sensitivity
      and specificity for the new PCR assay were 96.3% and 100% respectively. The
      procedure described is easy to perform, does not require special equipment and
      has produced excellent results. It deserves serious consideration for routine
      clinical microbiology laboratory use.

PMID- 10063478
TI  - A survey of percutaneous/mucocutaneous injury reporting in a public teaching
      hospital.
AB  - Our objective was to determine if healthcare workers were reporting all
      percutaneous and/or mucocutaneous injuries and to use such data to formulate
      appropriate interventions. The Infection Control Department distributed anonymous
      surveys of healthcare personnel between 1992 and 1995. The elicited information
      included the number of percutaneous and mucocutaneous injuries experienced and
      reported in the last five years and the reasons for not reporting every exposure
      when applicable. Five hundred and forty nine surveys were received, from
      physicians, dentists, registered nurses, licensed vocational nurses, nurses
      aides, and operating room technicians. Overall, of the 549 respondents, 45% (245)
      had no injuries, 30% (163) had been injured and had reported all injuries, and
      26% (141) had not reported all injuries. Reasons for not reporting included
      sterile/clean needlestick (39%), little or no perception of risk to employee
      (26%), too busy (9%), and dissatisfaction with follow-up procedures (8%). Reasons
      stated for not reporting injuries indicate a need for continued education in the
      risk of acquiring blood-borne pathogens from such injuries. The results also
      illustrate the importance of targeting prevention efforts to specific groups,
      such as physicians, that would not be identified by routine reporting mechanisms.

PMID- 10063479
TI  - Waterbirths: regional audit of infection control practices.
AB  - Waterbirths are increasingly being offered as an option, although concerns about
      associated infection risks have been expressed. We undertook an audit of current
      practice in our region to help formulate an infection control policy.
      Questionnaires were sent to the Infection Control Nurses at 16 centres, with a
      request for completion in conjunction with the Infection Control Doctor. Fourteen
      (88%) centres responded, 11 of which carried out waterbirthing. Eight had
      permanent on-site pools, of which five were permanently plumbed in and provided
      with separate water inlets and outlets. All eight centres had infection control
      policies for waterbirthing. Six policies included care of the pool using
      detergent and disinfectant (chlorine-releasing compounds) and two using detergent
      alone. In none of the centres were the mothers tested for blood-borne viruses.
      Six centres collected data on infection in mother or child, and two carried out
      regular microbiological testing of pools. Infection control policies for
      waterbirths should include instructions for pool maintenance and decontamination,
      for prevention of legionella, for universal precautions and for use of personal
      protective equipment. Post-natal surveillance of mothers and babies is required
      in order to ascertain infection rates.

PMID- 10063480
TI  - Is routine screening for conventional enteric pathogens necessary in sporadic
      hospital-acquired diarrhoea?

PMID- 10063481
TI  - Catheter-related bacteraemia in children in Greece.

PMID- 10063482
TI  - The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to
      the dopamine hypothesis of schizophrenia.
AB  - Administration of noncompetitive NMDA/glutamate receptor antagonists, such as
      phencyclidine (PCP) and ketamine, to humans induces a broad range of
      schizophrenic-like symptomatology, findings that have contributed to a
      hypoglutamatergic hypothesis of schizophrenia. Moreover, a history of
      experimental investigations of the effects of these drugs in animals suggests
      that NMDA receptor antagonists may model some behavioral symptoms of
      schizophrenia in nonhuman subjects. In this review, the usefulness of PCP
      administration as a potential animal model of schizophrenia is considered. To
      support the contention that NMDA receptor antagonist administration represents a
      viable model of schizophrenia, the behavioral and neurobiological effects of
      these drugs are discussed, especially with regard to differing profiles following
      single-dose and long-term exposure. The neurochemical effects of NMDA receptor
      antagonist administration are argued to support a neurobiological hypothesis of
      schizophrenia, which includes pathophysiology within several neurotransmitter
      systems, manifested in behavioral pathology. Future directions for the
      application of NMDA receptor antagonist models of schizophrenia to preclinical
      and pathophysiological research are offered.

PMID- 10063483
TI  - Meta-analysis of the reversible inhibitors of monoamine oxidase type A
      moclobemide and brofaromine for the treatment of depression.
AB  - The reversible inhibitors of monoamine oxidase type A (RIMAs) are a newer group
      of antidepressants that have had much less impact on clinical psychopharmacology
      than another contemporary class of medications, the selective serotonin reuptake
      inhibitors (SSRIs). The RIMAs agents are distinguished from the older monoamine
      oxidase inhibitors (MAOIs) by their selectivity and reversibility. As a result,
      dietary restrictions are not required during RIMA therapy, and hypertensive
      crises are quite rare. In this article, we describe a series of meta-analyses of
      studies of the two most widely researched RIMAs, moclobemide (MOC; Aurorex) and
      brofaromine (BRO). Our findings confirm that both BRO and MOC are as effective as
      the tricyclic antidepressants, and they are better tolerated. However, BRO is not
      being studied at present for reasons unrelated to efficacy or side effects. MOC,
      which is available throughout much of the world (but not the United States), is
      significantly more effective than placebo and, at the least, comparable to the
      SSRIs in both efficacy and tolerability. For MOC, higher dosages may enhance
      efficacy for more severe depressions. We also found evidence that supports
      clinical impressions that MOC is somewhat less effective, albeit better
      tolerated, than older MAOIs, such as phenelzine or tranylcypromine. Little
      evidence has yet emerged to suggest that the RIMAs share older MAOIs' utility for
      treatment of depressions characterized by prominent reverse neurovegetative
      features. Based on available evidence, the RIMAs appear to have a limited, but
      useful, role in the differential therapeutics of the depressive disorders.

PMID- 10063484
TI  - The Ca2+ channel blockade changes the behavioral and biochemical effects of
      immobilization stress.
AB  - We investigated how the effects of chronic immobilization stress in rats are
      modified by Ca2+ channel blockade preceding restraint sessions. The application
      of nifedipine (5 mg/kg) shortly before each of seven daily 2 h restraint sessions
      prevented the development of sensitized response to amphetamine as well as the
      stress-induced elevation of the densities of L-type Ca2+ channel in the
      hippocampus and significantly reduced the elevation of the densities of
      [3H]nitrendipine binding sites in the cortex and D1 dopamine receptors in the
      limbic forebrain. Neither stress, nor nifedipine affected the density of alpha 1
      adrenoceptors and D1 receptors in the cerebral cortex nor D2 dopamine receptors
      in the striatum. A single restraint session caused an elevation of blood
      corticosterone level that remained unaffected by nifedipine pretreatment, but the
      reduction of this response during the eighth session was significantly less
      expressed in nifedipine-treated rats. We conclude that L-type calcium channel
      blockade prevents development of several stress-induced adaptive responses.

PMID- 10063485
TI  - Regional differences in the inhibition of mouse in vivo [3H]Ro 15-1788 binding
      reflect selectivity for alpha 1 versus alpha 2 and alpha 3 subunit-containing
      GABAA receptors.
AB  - The benzodiazepines flunitrazepam, diazepam, and Ro 15-1788 and the beta
      carboline DMCM bind with equivalent affinity to the benzodiazepine binding site
      of GABAA receptors containing different alpha subunits (i.e., alpha 1, alpha 2,
      alpha 3, or alpha 5); whereas, the triazolopyridazine CL 218,872 and
      imidazopyridine zolpidem have higher affinity for alpha 1 subunit-containing
      GABAA receptors. In the present study, the in vivo binding of [3H]Ro 15-1788 in
      mouse cerebellum and spinal cord was used to establish the occupancy of the
      benzodiazepine binding site of GABAA receptors containing primarily alpha 1 and
      alpha 2/alpha 3 subunits, respectively. Thus, the nonselective compounds
      flunitrazepam, diazepam, and DMCM all produced a similar inhibition of binding in
      cerebellum and spinal cord (respective ID50 values of 0.2 to 0.3 mg/kg, 2 mg/kg,
      and 10 mg/kg i.p.); whereas, the alpha 1 selective compounds CL 218,872 and
      zolpidem were more potent at inhibiting [3H]Ro 15-1788 binding in the cerebellum
      (ID50 values 4.5 mg/kg and 10 mg/kg i.p.) compared to the spinal cord (ID50
      values 12 mg/kg and > 30 mg/kg i.p.). Thus, the reduction of in vivo f[3H]Ro 15
      1788 binding in tissues containing alpha 1 and alpha 2/alpha 3 receptor
      populations reflects the in vitro affinities of subtype selective compounds and
      should help to interpret the behavioral profile of such compounds.

PMID- 10063486
TI  - Mixed agonist-antagonist properties of clozapine at different human cloned
      muscarinic receptor subtypes expressed in Chinese hamster ovary cells.
AB  - We recently reported that clozapine behaves as a partial agonist at the cloned
      human m4 muscarinic receptor subtype. In the present study, we investigated
      whether the drug could elicit similar effects at the cloned human m1, m2, and m3
      muscarinic receptor subtypes expressed in the Chinese hamster ovary (CHO) cells.
      Clozapine elicited a concentration-dependent stimulation of [3H]inositol
      phosphates accumulation in CHO cells expressing either the m1 or the m3 receptor
      subtype. Moreover, clozapine inhibited forskolin-stimulated cyclic AMP
      accumulation and enhanced [35S] GTP gamma S binding to membrane G proteins in CHO
      cells expressing the m2 receptor. These agonist effects of clozapine were
      antagonized by atropine. The intrinsic activity of clozapine was lower than that
      of the full cholinergic agonist carbachol, and, when the compounds were combined,
      clozapine potently reduced the receptor responses to carbachol. These data
      indicate that clozapine behaves as a partial agonist at different muscarinic
      receptor subtypes and may provide new hints for understanding the receptor
      mechanisms underlying the antipsychotic efficacy of the drug.

PMID- 10063487
TI  - Carbamazepine-induced upregulation of adenosine A1-receptors in astrocyte
      cultures affects coupling to the phosphoinositol signaling pathway.
AB  - The anticonvulsant and antibipolar drug carbamazepine (CBZ) is known to act as a
      specific antagonist at adenosine A1-receptors. After a 3-week application of CBZ,
      A1-receptors are upregulated in the rat brain. We have investigated the
      consequences of this upregulation for the A1-receptor-mediated signal
      transduction in primary astrocyte cultures from different regions of the rat
      brain. CBZ treatment for 10 days had no effect on adenosine A1-receptor mRNA
      expression in cultures with high basal A1-receptor mRNA levels, but increased A1
      receptor mRNA in cultures exhibiting low basal A1-receptor mRNA levels. This
      upregulation of A1-receptor mRNA was accompanied by an upregulation or induction
      of A1-receptor-mediated potentiation of PLC activity, a property that was not
      found in these cultures before CBZ treatment. Thus, CBZ treatment for 10 days
      induces a new quality of adenosine A1-receptor-mediated signal transduction in
      cells that express low basal A1-receptor numbers.

PMID- 10063488
TI  - Ethanol as a hypnotic in insomniacs: self administration and effects on sleep and
      mood.
AB  - The purpose of this study was to assess the effects of low ethanol doses on sleep
      and mood and to assess its reinforcing effects used as a hypnotic. Twenty healthy
      adults, aged 21-45 yrs, all moderate social drinkers, were studied: eleven
      subjects had insomnia and nine were normal sleepers, as documented by clinical
      polysomnography. On two sampling nights each, ethanol (0.5 g/kg) or placebo was
      administered before sleep in color-coded cups presented in three doses (0.2, 0.2,
      and 0.1 g/kg) separated by 15 min. On three subsequent nights subjects chose
      their preferred presleep beverage (0.2 g/kg ethanol or placebo) based on cup
      color and were given an opportunity for 3 additional refills (0.2 g/kg each) of
      the chosen beverage at 15 min intervals, yielding a total possible dose of 0.8
      g/kg. Insomniacs chose ethanol 67% of nights and normals 22%. Insomniacs chose
      significantly more ethanol refills than normals for an average nightly dose of
      0.45 g/kg and normals took significantly more placebo refills. On the sampling
      nights 0.5 g/kg ethanol reduced REM sleep for both groups for the 8-hr sleep
      period and in insomniacs increased stage 3-4 sleep and reduced stage 1 sleep
      during the first half of the night to the level seen in the normals. Other sleep
      variables were not altered in either group or halves of the night. Presleep
      improvements in the Profile of Mood States tension and concentration factors were
      also associated with ethanol administration. Thus, acutely, both sleep and mood
      effects appear to be associated with the reinforcing effects of ethanol as a
      hypnotic for insomniacs.

PMID- 10063489
TI  - Effects of mCPP on the extracellular concentrations of serotonin and dopamine in
      rat brain.
AB  - Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5
      mg/kg) induced a marked and dose-related increase in extracellular concentrations
      of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo
      microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH)
      strain. Indicating that the effect of mCPP was caused by a reversal of the
      serotonin transporter, it was antagonized by pretreatment with the serotonin re
      uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration
      of the sodium channel blocker tetrodotoxin (TTX; 1 microns). mCPP was also shown
      to induce an increase in extracellular concentrations of dopamine in the nucleus
      accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the
      Sprague-Dawley (SD) strain; this effect of mCPP was, however, much weaker (125
      170% of baseline) than the effect on serotonin; moreover, it seems to be TTX
      sensitive. In anesthetized SD rats, mCPP induced a moderate reduction of nigral
      dopamine cell firing rate; supporting the assumption that this effect is
      secondary to the observed increase in dopamine release, it was blocked by
      pretreatment either with the dopamine synthesis inhibitor alpha-methyl-para
      tyrosine or with the dopamine D2 receptor antagonist haloperidol. In conclusion,
      the results suggest that mCPP induces a marked, TTX-insensitive increase in
      serotonin release in rat brain, but only a modest and TTX-sensitive increase in
      the extracellular levels of dopamine.

PMID- 10063490
TI  - A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in
      cocaine-dependent subjects.
AB  - We have previously shown that nicotine enhances cue-induced cocaine craving. In
      the present study, the effects of a nicotine antagonist, mecamylamine, on cue
      induced cocaine craving were investigated. Twenty-three cocaine-dependent
      patients, all cigarette smokers, were randomly assigned to mecamylamine (2.5 mg
      tablet) or placebo in a single-dose, placebo-controlled, crossover, double-blind
      study. Craving and anxiety were measured before and after cocaine cues with
      visual analog scales for desire to use cocaine and mood. Skin conductance, skin
      temperature and heart rate were recorded before and during cocaine cues.
      Following exposure to cocaine cues, all patients reported an increase in cocaine
      craving and anxiety relative to the precue measures. Cue exposure also produced
      an increase in skin conductance and decrease in skin temperature. The cue-induced
      increase in cocaine craving was reduced, while the cue-induced skin conductance
      and temperature responses were unaffected, by mecamylamine. These findings show
      that cue-induced cocaine craving is attenuated by mecamylamine. Further study on
      the use of mecamylamine in relapse prevention programs are suggested.

PMID- 10063491
TI  - [Basic approaches in minimally invasive cardiac surgery (MICS) and its
      selection].
AB  - Recently, minimally invasive cardiac surgery (MICS) has been developed and
      popularized as a less stressful and less invasive technique in the field of
      cardiac surgery. There are eight currently available MICS approaches for open
      heart surgery. The optimum approach should be selected for each patient based on
      the results of preoperative examination including chest X-ray, computed
      tomography, and angiography. Between December 1996, when we first introduced MICS
      for mitral repair, and the end of November 1998, we performed MICS in 67 patients
      [excluding cases of MIDCAB]. These included 11 patients who received the Port
      Access (Heartport, Inc.) system. Although no patients died in hospital stay, one
      died of cerebrovascular bleeding eight months later. All patients were evaluated
      in the outpatient department as being NYHA class I. In view of future
      technological progress, we expect that MICS will gradually become more widespread
      in cardiac surgery.

PMID- 10063492
TI  - [Minimally invasive mitral surgery: mitral valve repair with a right-sided
      partial sternotomy].
AB  - We describe our concept and the results of mitral valve repair using a right
      sided partial sternotomy. We performed mitral valve repair using this method in
      50 patients with severe MR between April 1997 and October 1998. In 10 patients in
      whom good exposure was not attained, we changed to the ordinary full-sternotomy
      or T-shaped partial sternotomyprocedure. Forty patients with good exposure
      underwent successful mitral valve repair. The sites of repair were anterior in 15
      cases, posterior in 16, and both in 9. There was no mortality, and intraoperative
      TEE performed in all 40 patients revealed that all had trivial or no
      regurgitation. The right-sided partial sternotomy (open door method) is a safe
      and useful method for minimally invasive valve Surgery. A better quality of life
      compared with traditional median sternotomy can be ensured for patients
      undergoing minimally invasive cardiac surgery only when receive the best-quality
      Surgery is performed.

PMID- 10063493
TI  - [Minimally invasive cardiac surgery for aortic valve disease].
AB  - Recent surgical advances leading to good operative results have contributed to
      the trend to useminimally invasive approaches, even in cardiac surgery. Smaller
      incisions are clearly more cosmetically acceptable to patients. When using a
      minimally invasive approach, it is most important to maintain surgical quality
      without jeopardizing patients. A good operative visual field leads to good
      surgical results. In the parasternal approach, we use a retractor to harvest an
      internal thoracic artery in coronary artery bypass surgery. Retracting the
      sternum upward allows for a good surgical view and permits the use of an arch
      cannula rather than femoral cannulation. When reoperating for aortic valve
      repair, the j-sternotomy approach requires less adhesiolysis compared with the
      traditional full sternotomy. No special technique is necessary to perform aortic
      valve surgery using the j-sternotomy approach. However, meticulous attention must
      be paid to avoiding left ventricular air embolisms to prevent postoperative
      stroke or neurocognitive deficits, especially when utilizing a minimally invasive
      approach. Transesophageal echo is useful not only for monitoring cardiac function
      but also for monitoring the persence of air in the left ventricle and atrium.
      This paper compare as the degree of invasion of minimally invasive cardiac
      surgery and the traditional full sternotomy. No differences were found in the
      occurrence of systemic inflammatory response syndrome between patients undergoing
      minimally invasive cardiac surgery and the traditional technique. Therefore it is
      concluded that minimally invasive surgery for patients with aortic valve disease
      may become the standard approach in the near future.

PMID- 10063494
TI  - [Minimally invasive cardiac surgery--the efficacy of right parasterna approach].
AB  - The recent concepts of minimally invasive surgery have affected even
      cardiovascular surgery. Especially, the desire to lessen incisional pain and
      hospital stay has made minimally invasive cardiac surgery (MICS) desirable.
      However, its efficacy is still controversial. To investigate this goal, we
      assessed the efficacy of avoidance of median sternotomy through right parasternal
      approach in view of the postoperative bleeding, % transfusion, postoperative
      intubation period, degree of incisional pain and serum level of cytokines.
      Patients with mitral valve disease or atrial septal defects were divided into the
      MICS (M) group and the control (C) group. In the M group, operations were
      performed through right parasternal incision under cardiopulmonary bypass (CPB)
      instituted by placing a venous cannula directly into superior vena cava and
      arterial and the other venous cannulae into femoral artery and vein. On the other
      hand, in the C group, operations were performed through median sternotomy under
      conventional CPB. There were no significant differences in CPB and AXC time
      between two groups. The M group showed significantly lower value in the
      postoperative bleeding volume, % transfusion, postoperative intubation time.
      Patients in the M group showed higher satisfaction of small incision as compared
      with those in the C group. Serum level of IL-8 after CPB was significantly lower
      in the M group than in the C group. These results suggested that MICS for mitral
      disease or ASD appears to be less invasive when median sternotomy is avoided.
      This suggest that MICS is a promising and contributed approach for open heart
      surgery to improve the QOL of the patients.

PMID- 10063495
TI  - [Indications for and limitations of minimally invasive cardiac surgery with the
      lower ministernotomy approach].
AB  - The chief benefits of small skin incisions are reduced patient discomfort,
      accelerated recovery, and cosmetic satisfaction without compromising the quality
      of surgery. Since April 1997, the lower ministernotomy approach without femoral
      cannulation has been performed in 43 patients in the authors' institutions. The
      indications for this approach were initial single valve surgery and secundum-type
      atrial septal defect. Cases of aortic valve regurgitation that could be repaired,
      and aortic stenosis that necessitated annular enlargement were excluded. Among
      patients with mitral valve disease, those with chronic atrial fibrillation were
      excluded frpm undergoing the Maze procedure and those reguiring chordal
      reconstruction for anterior leaflet were also excluded. Mitral valve repair for
      mitral regurgitation was performed in 8 patients, and open mitral commissurotomy
      in 2. Mitral valve replacement was performed in 3 patients and aortic valve
      replacement in 13. Closure of an atrial septal defect was carried out in 18
      cases. An approximately 10-cm median skin incision was made, and a ministernotomy
      with a lower semitransverse division (inverted L-shape) was carried out.
      Cardiopulmonary bypass was initiated with ascending aortic cannulation and right
      angled venous cannulae in the superior and inferior vena cava for mitral valve
      disease. Single venous cannulae from the right atrial appendage was used for
      aortic valve disease. Surgery was performed with mild hypothermia and
      intermittent tepid blood cardioplegia with diltiazem. A rigid 30-degree angle
      scope held by a videoscope holder with a flexible arm was used for mitral valve
      surgery. There were one hospital death due to perioperative myocardial infarction
      and pulmonary embolism. There was one reopening for bleeding which resulted in
      methicillin-resistant Staphylococcus aureus mediastinitis. However, the patients
      was discharged after rectal muscle flap repair. There was one reoperation for
      mitral valve repair due to hemolysis. The improvement of surgical instruments and
      materials will further facilitate this procedure.

PMID- 10063496
TI  - [Lower mid-line skin incision and minimal sternotomy in pediatric open heart
      surgery--an alternative cosmetic approach].
AB  - Full median sternotomy has been the standard approach for open heart surgery.
      However, it leaves an unsightly surgical scar. We therefore designed a lower mid
      line skin incision and minimal sternotomy approach as a cosmetic alternative.
      Since February 1993, 78 pediatric patients with congenital heart disease have
      undergone this open heart surgery procedure. Their ages ranged from 1 month to 13
      years (median: 2 years and 7 months) and body weights ranged from 2.4 to 43 kg
      (median: 11.5 kg). Thirty-one patients had atrial septal defect, 34
      perimembranous ventricular septal defect, 9 subpulmonary ventricular septal
      defect, and 4 other cardiac anomalies. All cannulations for cardiopulmonary
      bypass could be performed through this approach. No patients required conversion
      to standard median sternotomy and no peri- or postoperative complications related
      to this approach, such as injury to the great artery and vein, air embolism, or
      sternal deherence, were noted. This approach is technically easy and an excellent
      cosmetic approach in pediatric open heart surgery.

PMID- 10063497
TI  - [Partial median sternotomy for pediatric cardiac surgery].
AB  - In order to minimize scarring and thereby improve the postoperative cosmetic
      appearance of pediatric cardiac surgery patients, we perform partial median
      sternotomy incisions. A short midline skin incision, from 1 to 2 cm below the
      articular notch of the second rib to the xiphoid process, is made. The sternum
      was divided from the xiphoid process to the articular notch of the second rib.
      The thymus is mobilized and the pericardium incised longitudinally. The aorta and
      superior and inferior vena cava are mobilized to facilitate direct cannulation.
      Cardiopulmonary bypass is instituted in the usual fashion. Twenty-four pediatric
      patients underwent repair of cardiac anomalies through a partial median
      sternotomy incision at our institution between June 1997 and September 1998. The
      average age of the patients was 4 years and 4 months (range, 4 days to 12 years)
      and the average weight was 16.0 kg (range, 3.2 to 40.5 kg). Cases included 13 VSD
      (ventricular septal defect) [including one DCRV (double chambered right
      ventricle) and one PS (pulmonary stenosis)], 9 ASD (atrial septal defect), one
      ECD (endocardial cushion defect), and one DORV (double outlet right ventricle)
      with mitral atresia. All patients were extubated within 3 hours after surgery and
      the average length of the ICU stay was within 24 hours (except for one 4-day-old
      baby who died of LOS (low cardiac output syndrome) on the 16th postoperative
      day). There were no wound infections or hospital mortalities. In our experience,
      this approach is safe, provides good exposure, and provides excellent cosmetic
      results.

PMID- 10063498
TI  - [Attitude of surgeons].

PMID- 10063499
TI  - [Surgical management of pulmonary metastases].
AB  - The results of surgical resection for pulmonary metastases from colorectal,
      breast, and renal cell carcinomas, soft tissue sarcoma, and osteosarcoma are
      reviewed. The number of pulmonary metastases, the presence of hilar or
      mediastinal involvement, and extrapulmonary foci are discussed in terms of
      surgical treatment. The size of pulmonary tumors or tumor doubling time has no
      significant effect on survival, while the number of metastatic foci does.
      Although a slight survival advantage has been noted for patients without hepatic
      metastases from colorectal cancer before pulmonary metastases occur, the
      difference in survival rates among patients with and without hepatic metastases
      is not significant. The role of surgery is less clear in breast cancer patients,
      and therefore further prospective study is considered essential. Higher relapse
      rates have been reported in patients with soft tissue sarcoma and osteosarcoma,
      although patients with these metastases can achieve long-term survival after a
      second metastasectomy. VATS is not be recommended for metastatic cancer surgery,
      because intraoperative identification of metastatic foci is often difficult.

PMID- 10063500
TI  - [A case of idiopathic intussusception of the stomach].
AB  - A 73-year-old man was admitted to our hospital because of vomiting. A fist-sized
      tumor with tenderness was palpated on his epigastric region. Fluoroscopic
      examination of the stomach showed narrow body and dilated antrum with
      intussusception. Endoscopic findings revealed fold convergence to the antrum.
      Intraoperatively, the body of the stomach was invaginated into the antrum with
      hepatoduodenal ligament. It was difficult to repair or resect, and a
      gastrojejunostomy was performed. On the 10th operative day, fluoroscopic
      examination of the stomach showed no intussusception of the stomach and no lesion
      in the upper gastrointestinal tract. To our knowledge, such cases of idiopathic
      intussusception of the stomach are rare.

PMID- 10063501
TI  - [A case of fibrous histiocytoma of the appendix with twisted stalk].
AB  - A 74-year-old man consulted this hospital with the chief complaint of lower right
      abdominal pain on February 13, 1998. He was hospitalized, subjected to
      abdominalechography and CT, and diagnosed as having subileus caused by an
      intraperitoneal tumor. Surgery was performed on February 25, 1998. When the
      abdomen was incised, a chicken egg-sized tumor at the end of theappendix were
      found. In addition, the stalk of the appendix was twisted. Appendectomy was
      therefore performed. Upon histopathological examination, it was found that the
      submucosal tumor originated at the end of the appendix, and proliferation of
      spindle-shaped fibroblast-like cells and histocytic oval cells was observed in
      the tumor. Since various histiocyte markers were positive upon immunohistological
      examination, the tumor was considered to be of histiocytic origin. However, the
      tumordid not exhibit polymorphism, heteromorphism, or mitotic figures which would
      confirm a diagnosis of malignant fibrous histiocytoma. It was thus diagnosed as a
      fibrous histiocytic tumor on the borderline between malignant and benign. We
      report the present case because the occurrence of a primary fibrous histiocytoma
      in an appendix of which the stalk is twisted is very rare.

PMID- 10063502
TI  - [Mitral regurgitation due to mitral valve prolapse associated with epidermolysis
      bullosa: case report].
AB  - Mitral valve prolapse (MVP) has been associated with several connective tissue
      disorders, including Marfan's syndrome, Ehlers-Danlos syndrome, and
      pseudoxanthoma elasticum. We present a case of MVP in a patient with
      epidermolysis bullosa. The authors are aware of only one previously reported case
      of this association. A 49-year-old man with a history of epidermolysis bullosa
      since childhood was admitted to our institution due to dyspnea on effort. On
      general examination he was observed to have alopecia, deformities in his nails,
      and fusions of his fingers. Transesophageal echocardiography confirmed the
      presence of MVP. In addition, coronary angiography showed three-vessel disease.
      Mitral valve replacement (ATS valve 25 mm) and coronary artery bypass grafting
      (left internal thoracic artery-LAD) were performed. The resected mitral valve
      (anterior leaflet) contained the area of the myxomatous lesion histologically.
      The pathological mechanism of epidermolysis bullosa is thought to be the
      destruction of collagen fibers due to increased levels of enzyme collagenase.
      Therefore there may be a common cause of MVP and epidermolysis bullosa based upon
      an abnormality of collagen metabolism.

PMID- 10063503
TI  - [Efficacy of temporary heart arrest induced by intravenous ATP in endoluminal
      grafting].

PMID- 10063504
TI  - [New research and considerations in managing minimally conscious coma patients].
AB  - The "Wachkoma", minimally conscious state (synonyms in use: "apallic syndrome",
      "vegetative state"), is a severe, complex condition arising from brain damage of
      diverse etiologies, for which definitional consensus does not exist
      internationally; it gives rise to frequent misdiagnosis and carries substantial
      insecurities concerning treatment outcomes. In the framework of expanding early
      rehabilitation, however, recent years have seen a distinct shift away from a
      defect-oriented, reductionist view towards a relational-medicine based
      understanding of patients with severe brain damage, seeking to gain a
      comprehensive perception of the patient's altered physical existence and taking a
      multidisciplinary--nursing, medical, therapeutic and neuropsychological-
      perspective which includes the patient's relatives and family. Historically, a
      transition is under way away from the classical brain-pathology focus toward a
      neuropsychologically grounded, differentiated perspective. Along with in-depth
      differential diagnostics and assessment of rehab potentials (early intervention
      diagnostics), comprehensive intervention measures are initiated as early as
      possible by an interdisciplinary team. These include "coma stimulation" measures,
      body language forms of interaction ("dialogue management"), and technical
      communication devices. By building long-term care assistance in ambulatory and
      residential service delivery systems ("small social network"), social
      reintegration of these very severely affected patients is attempted, involving
      the familial and social resources available. Recurrently raised within the
      bioethical discourse, demands to consider doctor-assisted dying or food
      withdrawal are to be rejected from a clinical, medical and social-ethical
      perspective.

PMID- 10063505
TI  - [Minimally conscious coma patients--patient positioning systems in general
      practice].
AB  - With a view to optimizing the positional management of patients with severe
      neurological damage, five positioning systems with different operating principles
      were submitted to suitability trials in a clinical neurological rehabilitation
      setting. The patients included were in the "Wachkoma", the minimally conscious
      state (i.e., in neurological early rehabilitation phase B). The experience
      collected by the various professions involved in positional management over a
      trial period of six months is summarized in the present report, indicating that
      none of the positioning systems used has been suitable for all patients alike.
      Hence, various items were compiled in a checklist to enable better estimation of
      each system's suitability in light of the individual patient, with muscle tone,
      body weight, skin condition, degree of mobilization and spontaneous movement the
      essential criteria in patient assessment. This checklist now permits identifying
      the positioning systems suitable for the individual patient in an economical
      manner, and lengthy positioning trials can be dispensed with to a large extent.

PMID- 10063506
TI  - [Service expectations facing Saxony's newly established social psychiatric
      services. Attitudes of established neurologists, physicians in psychiatric
      clinics and social psychiatry service staff].
AB  - In the wake of the disintegration of the policlinical system which had prevailed
      in the former German Democratic Republic, far-reaching restructuring has become
      necessary in the "new" German laender in the field of complementary psychiatric
      care. Establishment throughout the state of Saxony of a uniform outreach-based
      ambulatory service ranks as a first component towards building regionalized
      community psychiatric networks. In light of some twenty years of experience in
      the old laender, this function is considered a task of the Social Psychiatric
      Services ("Sozialpsychiatrische Dienste", SPDIs). The present study had been
      directed at a state-wide investigation of the expectations community-practice
      psychiatrists (n = 165), physicians in psychiatric clinics (n = 95) and staff
      working in SPDIs (n = 138) in Saxony hold regarding service programmes and
      operating methods of these newly established service delivery structures. Given
      the high return rates in this anonymous postal questionnaire study, the findings
      presented are considered near-representative. A concurrent finding for all of the
      groups interviewed, expectations concerning the client population to be serviced
      by the SPDIs focus on the group of persons with chronic mental illness. Also, the
      expectations expressed concerning major care/therapeutic services to be rendered
      by the SPDIs concur in their emphasis on a core area of immediately client
      oriented SPDI activities. Between the two medical groups, a major difference
      found is that community-practice psychiatrists more frequently expect high SPDI
      commitment regarding sociotherapeutic programmes at an institutional level,
      whereas clinical physicians expect them to focus on taking over medical therapies
      in the narrower sense. The expectations SPDI staff hold relative to the
      therapeutic services to be rendered by themselves go beyond the scope of what has
      so far been implemented in their current activity, and qualitative content
      analyses are presented in the article for each of the areas concerned. Along with
      better staffing levels, removal of in-service organizational and further
      education deficits are identified by SPDI staff as the two main requirements for
      stabilizing their operations. In order to counter undue burdening of the SPDI
      with service expectations and to enable a more clear-cut positioning of its
      programme structures within a complex psychosocial service delivery system, it is
      necessary--at least in the state of Saxony--that further needs-oriented
      establishment and/or extension of community-based psychiatric services and
      agencies take place.

PMID- 10063507
TI  - [Rehabilitation for psychiatric and handicapped patients."Haus Schutz" study of
      experiences and follow-up of rehabilitation of psychiatric and handicapped
      patient care 1992-1995].
AB  - In the framework of a 1992-1995 follow-up study at the Hessian RPK facility Haus
      Schutz for medical/vocational rehabilitation of persons with mental illness, a
      total of 216 rehabilitees are described on a number of parameters:
      success/failure, community-relatedness/remoteness, vocational
      training/occupation, duration of occupational activity, duration of mental
      illness, living situation, duration of service provision, as well as symptom
      change in different syndromes. It is found that a holistic, individualized
      treatment approach will enable more effective use of client resources as well as
      reducing total stay to a more manageable length, without adverse influence on
      treatment outcome.

PMID- 10063508
TI  - [Rehabilitation of psychiatric patients by half-way house admission--a
      catamnestic study].
AB  - In order to observe the course of rehabilitation of mentally ill persons a
      catamnestic study was done of 16 mainly schizophrenic former residents of the
      halfway house for mentally ill in Nuremberg. Along with the rehospitalization
      rate, the criteria for success were progress in the living and working fields.
      Concerning the course of illness and independent living very good results were
      found for the rehabilitation course. Reintegration into the working process could
      be advanced during the stay, stagnated however after the stay. Classifying the
      course of rehabilitation, overall or partial success was achieved in more than
      80% of the patients interviewed. The stay in a halfway house, hence, is a good
      possibility for medical rehabilitation of younger patients with long-term mental
      illness. However, it also turned out that out-patient follow-up treatment and
      care is of great importance for the social relationships of the often isolated
      patients.

PMID- 10063509
TI  - [Occupational rehabilitation of former drug addicts--experiences of the Isney
      Stephanuswerk].
AB  - Rehabilitees who have completed substance withdrawal treatment are among the
      special target groups for vocational rehabilitation measures. It in particular is
      at the transition from the primarily medically focussed phase of substance
      withdrawal treatment into the phase of vocational rehabilitation that this
      population has to cope with substantial adjustment problems, with the consequence
      of frequent, and occasionally massive, relapse into substance abuse, and hence
      not only temporary interruption of the vocational rehabilitation measure. From
      the long years of experience in working with this population at the Stephanuswerk
      Isny rehabilitation centre, an absolute need has emerged to offer particularly
      intensive social-educational and psychological follow-along supports during the
      phase of vocational rehabilitation. In response to these insights, cause-oriented
      action strategies have been devised seeking to prevent relapse among ex-dependent
      rehabilitees and/or assist them in their efforts to cope, in order to avoid drop
      outs from the vocational rehabilitation programme, with all the adverse
      consequences this would imply. These action strategies inter alia included
      drafting a catalogue of criteria applicable before client admission to the
      programme, as well as a catalogue of relapse-prevention measures during
      vocational rehabilitation. The core element of relapse prevention had been
      creating a prevention-focussed self-help group project, which, in terms of
      structure and concept, turned out a crucial stabilizing factor for relapse
      prevention or coping in rehabilitees at risk.

PMID- 10063510
TI  - [30 years rehabilitation preparatory courses and their role in the future
      exemplified by the Hamburg vocational promotion center].
AB  - Over the last 30 years, some 12,000 disabled people have participated in the pre
      rehabilitation courses ("Rehabilitationsvorbereitungslehrgange", RVL) offered by
      the Hamburg Vocational Training Centre (on average, some 75% of all rehabilitees
      have attended RVLs prior to their specific vocational retraining); 90% of them
      successfully, hence able to start their retraining as scheduled. In some 1000
      rehabilitees, the original occupational objective was reconsidered at the end of
      the course, attributable in particular to the fact that less than 40% of
      participants had gone through vocational assessment/work trial measures
      beforehand. Over these years, some 1400 rehabilitees obtained their lower
      secondary school leaving certificate (Hauptschulabschluss). Data collected over
      the last six years revealed that legasthenic disorders have been present in an
      average 7% of all RVL participants (a total of 50 persons a year), problems which
      were dealt with through special remedial measures to the extent that the
      prerequistites for successful retraining were achieved. Over the decades of their
      existence, the effectiveness of RVLs in preparing for successful vocational
      rehabilitation has been unchallenged. It is in particular the action competencies
      acquired in this preparatory phase already, such as team functioning,
      communication and project work skills as well as coping with the disablement
      present, that are found to complement and enhance the technical, occupation
      specific competencies acquired during the retraining, so that subsequent job
      application and placement in gainful employment will have far greater prospects
      of lasting success than had the RVL training been omitted.

PMID- 10063511
TI  - [Prevalence of low back pain in the population].
AB  - Studies on selected populations lead to biased estimates of the prevalence of
      back pain and associated factors. In order to obtain a valid picture of the
      prevalence of back pain this review article focuses on epidemiological studies in
      the general population. These studies can be divided into general health surveys
      and surveys with specific reference to back pain. General health surveys
      including questions on the prevalence of back pain have the greatest
      methodological differences because of different aims. Due to these different
      aims, different target populations and different methods these studies depict
      point prevalences between 0.8% and 41% and 1-year prevalences between 15% and
      56%. These general health surveys are contrasted with epidemiological studies
      especially designed to evaluate the prevalence of back pain. In these studies the
      point prevalence ranges between 14% and 42% and the lifetime period prevalence
      between 51% and 84%. Depending on the study reviewed the highest prevalence is
      found at age 50 to 64. This prevalence pattern may be explained by several
      effects that are discussed in this article. Severe forms of back pain increase
      even in the higher age groups, especially in women. Beside this effect the
      reviewed articles show either no difference between men and women or only a
      slightly higher prevalence in women. The problems faced by epidemiological
      studies on back pain, resulting from different definitions of "the back",
      severity, chronicity and different methodology, are discussed in detail.

PMID- 10063512
TI  - [Methodology and didactics of training children and adolescents in topical
      treatment of atopic dermatitis].
AB  - There are increasing numbers of education programmes for children and young
      people with atopic dermatitis. These also include directions for the treatment of
      atopic dermatitis. However, the methods to be followed and the treatment to be
      applied are usually not clearly defined or explained. Presented are the key
      aspects of the local treatment of atopic dermatitis to be taught to children. The
      introduction of a basic therapeutic concept helps sort out which are the best
      preparations to use, some with and others without active ingredients. The
      interactions between basic care, active ingredients and skin conditions are
      explained in such a way that children can understand them.

PMID- 10063513
TI  - [Ambulatory, interdisciplinary team work in the tension field between theory and
      practice--Vorarlberg social medicine organization].
AB  - Presented is the Social-Medical Organization active in the field of ambulatory
      neurological care of adults in Vorarlberg, Austria, offering interdisciplinary
      cooperation possibilities in terms of team consultation, case presentation and
      discussion, as well as supervision. Ambulatory interdisciplinary teamwork is
      situated in a theory-practice field of tension, with occupational training
      failing to teach interdisciplinary cooperation and interdisciplinarity role
      models not encountered either during practicals. The ensuing, deliberately
      identified problems and issues have been addressed in a planned process.
      Familiarization with the various occupational fields involved, with each field
      having its specific job profile, as well as the notions on cooperation among the
      various fields are presented. The role the various occupational fields have in
      neurological aftercare as well as existing job profile cliches are reflected
      upon. Communication is in addition hampered by the diversity of training contents
      in the various occupational fields. Focussing on case presentation and
      discussion, teams are considered a place for obtaining advice, for joint
      development of targets and strategies, and interdisciplinary interfacing is no
      longer perceived as threatening but as enriching and productive. The role of
      stronger family doctor inclusion in formulation therapy goals remains an issue as
      yet unsolved.

PMID- 10063514
TI  - [Indications for evaluation scales in quality assurance in rehabilitation--16].
AB  - Prognostic evaluations are necessary to predict efficiency and possible success
      in social medicine. For this reasons the "Integration Prognosis Index" (IPI) is
      giving criteria. The structure of the special indices are compiled under
      interdisciplinary aspects (by bio-socio-morphological interactionistic details).
      The IPI was proved by investigations on vocational integration (done by EAM and
      IMBA assessments). Because vocational integration is one aspect of participation
      classified by ICIDH-2 the importance of the IPI for quality assurance and for
      further social and therapeutic support could be demonstrated. Validity and
      Sensitivity was shown for structuring rehabilitative procedures. It is stressed
      that selectivity according to a priority principle is only acceptable in
      rehabilitation if all aspects of integration are realized in practice to improve
      the situations of handicapped people.

PMID- 10063515
TI  - Bacterial infection and related arthritides: what do we really know?

PMID- 10063516
TI  - Critical appraisal of molecular biology techniques for detecting bacteria in
      synovial specimens.

PMID- 10063517
TI  - Chlamydia species in human arthritides.

PMID- 10063518
TI  - Enterobacteria in reactive arthritis: Yersinia, Shigella, and Salmonella.

PMID- 10063519
TI  - Borrelia burgdorferi in Lyme arthritis and undifferentiated arthritis.

PMID- 10063520
TI  - What is the role of mycoplasmas in human inflammatory rheumatic disorders?

PMID- 10063521
TI  - Mechanisms of bacterial persistence in the host.

PMID- 10063522
TI  - Humoral immunity in Chlamydia trachomatis arthritis.

PMID- 10063523
TI  - Bacteria-specific T cells response. What role for HLA molecules?

PMID- 10063524
TI  - Unusual MHC-I genes and spondylarthropathies.

PMID- 10063525
TI  - Mycoplasma-induced arthritis in animals: relevance to understanding the
      etiologies of the human rheumatic diseases.

PMID- 10063526
TI  - A non-invasive murine model of chlamydia-induced reactive arthritis.

PMID- 10063527
TI  - Characteristics of arthritogenic bacteria. The bacteriologist's point of view.

PMID- 10063528
TI  - Interactions of pathogens with the host immune system: implications for the
      pathogenesis of reactive arthritis.

PMID- 10063529
TI  - Antibiotic trials in reactive arthritis.

PMID- 10063530
TI  - Trials evaluating antibiotics in rheumatoid arthritis: an overview.

PMID- 10063531
TI  - Antimicrobial effects of antiinflammatory drugs, antiinflammatory effects of
      antimicrobial drugs.

PMID- 10063532
TI  - Oral immunisation of swine with a classical swine fever vaccine (Chinese strain)
      and transmission studies in rabbits and sheep.
AB  - Seven experiments including a total of 47 pigs, 11 wild boars, 26 rabbits, 10
      hares and 16 sheep were carried out to assess the efficacy, safety and
      transmission of the Chinese vaccine strain of the classical swine fever virus
      (CSFV) administrated by the oral route. Within 3 weeks after oral vaccination, a
      clear seroconversion occurred in the pigs. Six weeks after vaccination,
      vaccinated pigs were fully protected against a virulent challenge. The C-strain
      was not isolated from tonsils, spleen, lymph nodes, thymus, saliva, urine and
      faeces of pigs within 4 days after oral vaccination. In one experiment,
      susceptible pigs were placed in direct contact with vaccinated pigs. None of
      these contact-exposed pigs became serologically positive for CSFV antibodies. It
      is concluded that the C-strain induces protection in pigs when administrated by
      the oral route and is not shed by vaccinated pigs. Serum anti-CSFV antibodies
      developed in seven out of eight wild boars vaccinated by the oral route. No
      vaccine virus was detected in the spleen and tonsils of these animals. The
      results in wild boar were in accordance with those obtained in domestic pigs.
      Sheep did not show any clinical signs after oral vaccination while rabbits had
      moderate hyperthermia and growth retardation. No clinical response to oral
      immunisation in hares was detected. At the end of the experiment, no sheep had
      detectable serum antibodies against CSFV, whereas a few vaccinated rabbits and
      hares became seropositive. None of the contact-exposed rabbits and hares
      seroconverted. These data indicate that the C-strain is safe for sheep and as
      expected, moderately or not pathogenic for rabbits and hares. These efficacy and
      safety studies on oral vaccination with the C-strain under experimental
      conditions provide essential information for further studies in wild boars under
      experimental and field conditions, including assays with baits to control a CSF
      epidemic.

PMID- 10063533
TI  - Duration of bluetongue viraemia and serological responses in experimentally
      infected European breeds of sheep and goats.
AB  - The duration of viraemia and the serological responses were studied in two breeds
      of sheep and two breeds of goats, experimentally infected with bluetongue (BT)
      virus serotype 4. Viraemia, detectable by cell culture and embryonated chicken
      egg inoculation, lasted from the third to sixth day until the 27th-54th day post
      infection (p.i.). Significant differences between sheep and goats were not
      recorded. Lesbos sheep and goats together appeared to have significantly longer
      viraemias (n = 9, mean 41.3 days) than east-Friesian sheep and Saanen goats (n =
      10, mean 30.4 days, p = 0.0039). Serological response was studied by competitive
      ELISA (c-ELISA) and agar gel immunodiffusion (AGID) tests. The c-ELISA was more
      sensitive in detecting BT virus antibodies in all animals than the AGID tests. No
      significant differences were observed between sheep and goats or between breeds.
      The epidemiological significance of subclinical infection and the extended BT
      virus viraemias in Lesbos sheep and goats, in relation to the maintenance of the
      virus and to overwintering is discussed.

PMID- 10063534
TI  - Porcine reproductive and respiratory syndrome virus and Haemophilus parasuis
      antigen distribution in dually infected pigs.
AB  - Immunohistochemical, viral and bacterial isolation techniques were used to study
      the distribution and localization of porcine reproductive and respiratory
      syndrome virus (PRRSV) and Haemophilus (H.) parasuis in experimentally infected
      pigs. Thirty pigs seronegative to PRRSV and H. parasuis were divided into four
      groups. Group A pigs (10 animals) were inoculated with both virus and bacteria;
      group B pigs (10 animals) were inoculated with bacteria, group C pigs (five
      animals) were inoculated with virus and group D pigs (five animals) were kept as
      negative controls. All pigs of groups A and C became infected with PRRSV,
      according to virological techniques used (immunohistochemistry, virus isolation
      and virus serology). Lung, heart and tonsils were the most frequently
      immunolabeled tissues, and monocyte/macrophage lineage cells were the target for
      PRRSV in all tissues. All pigs in groups A and B also became infected with H.
      parasuis based on immunohistochemical and bacterial isolation results. Serosal
      surfaces, lung and tonsils were the most frequently immunolabeled tissues, and
      bacteria were found in monocyte/macrophage lineage cells as well as within
      neutrophil cytoplasm. No differences in terms of bacterial distribution or
      localization in tissues of pigs of groups A and B were detected. These results
      suggest that there is no influence of the previous infection with PRRSV in the
      occurrence of H. parasuis infection.

PMID- 10063535
TI  - Susceptibility testing of Actinobacillus pleuropneumoniae in Denmark. Evaluation
      of three different media of MIC-determinations and tablet diffusion tests.
AB  - This study was conducted to compare the applicability of three different media in
      sensitivity testing of Actinobacillus pleuropneumoniae by means of MIC and tablet
      diffusion tests. The media used were: modified PPLO agar, chocolatized Mueller
      Hinton-II and Columbia agar supplemented with NAD. Seven antimicrobial agents
      were tested: ceftiofur, enrofloxacin, penicillin, spectinomycin, tiamulin,
      trimethoprim + sulfadiazine and tylosin, against 40 randomly selected A.
      pleuropneumoniae isolates. In general, good agreement was found between results
      obtained with all combinations of media, most antimicrobials tested and the two
      test systems. Some variations between media were observed for spectinomycin,
      tiamulin and tylosin. For ceftiofur and trimethoprim + sulfadiazine some isolates
      with low MIC-values were classified as resistant using tablet diffusion,
      indicating that the break points of resistance for these antimicrobials using the
      tablet diffusion tests need adjustment. Using current break points for resistance
      with MIC-determinations, all isolates tested susceptible to ceftiofur,
      enrofloxacin, penicillin, tiamulin and trimethoprim + sulfadiazine. A larger
      number of isolates tested resistant to spectinomycin and tylosin on all three
      media using both MIC determinations and tablet diffusion.

PMID- 10063536
TI  - Actin polymerization enhances Pasteurella haemolytica leukotoxicity.
AB  - Pasteurella haemolytica leukotoxin is cytotoxic to bovine leukocytes, causing
      increased cell membrane permeability, osmotic swelling, release of cytosolic
      proteins and cell lysis. These studies were designed to test if leukotoxin causes
      release of the cytoskeletal protein, actin, from bovine leukemia cells and if
      purified actin-influenced bacterial growth or leukotoxin production. Culture
      supernatants caused a 7-fold decrease in viability of bovine leukemia cells and
      increased cell permeability that was accompanied by release of beta-actin into
      the cell culture supernatant. Exposing P. haemolytica to purified actin solutions
      induced the conversion of monomeric G-actin to polymerized F-actin. This
      conversion was partially inhibited by bovine P. haemolytica immune, but not pre
      immune, serum. Loss of streptomycin resistance following treatment of the
      organism with acridine orange ablated the polymerizing activity. Incubation of P.
      haemolytica in the presence of purified F-actin did not affect growth but
      resulted in culture supernatant that had 3.0-3.9-fold greater leukotoxicity
      compared to medium alone or medium containing G-actin, heat-denatured actin or
      albumin. The effect of actin on leukotoxicity was concentration-dependent and
      directly associated with increases in secreted leukotoxin. The interaction
      between P. haemolytica and actin is potentially detrimental to the host by
      inducing polymerization of actin into insoluble filaments and by enhancing
      leukotoxicity.

PMID- 10063537
TI  - Relationship between resistance to complement, virulence and outer membrane
      protein patterns in pathogenic Escherichia coli O2 isolates.
AB  - To establish a possible relationship between resistance to complement, virulence
      and outer membrane protein banding patterns, ten E. coli O2 strains isolated from
      chickens with colibacillosis were studied for: (1) resistance to the bactericidal
      effect of complement by a quantitative microtiter method, (2) virulence, as
      determined by chicken lethality test, and (3) outer membrane protein banding
      patterns yielded by SDS-polyacrylamide gel electrophoresis. The ten isolates were
      classified into three groups: (1) Group 1, consisting of four isolates showed:
      (a) high resistance to complement, (b) high virulence, and (c) different pattern
      between 35 and 40 kDa with a weak peptide band at 35 kDa. (2) Group 2, consisting
      of one isolate showed: (a) high resistance to complement, (b) low virulence, and
      (c) a weak peptide band at 35 kDa. (3) Group 3, consisting of five isolates
      showed: (a) low resistance to complement, (b) low virulence, and (c) identical
      OMP pattern between 35 and 40 kDa exhibiting a strong peptide band at 35 kDa. The
      results suggest that high resistance to complement may be necessary but no
      sufficient for virulence and that OMP banding patterns may be a marker for
      virulence.

PMID- 10063538
TI  - Cytotoxic T-cell, delayed type hypersensitive and listeriolysin O responses in
      experimental bovine listeriosis.
AB  - Five different antigens of Listeria monocytogenes NCTC 11994 were assayed for
      their lymphoproliferative, cytotoxic, humoral and delayed type hypersensitivity
      (DTH) responses in experimentally infected calves. The antigens used were culture
      filtrate antigen (CFA), listeriolysin O (LLO), sonicated antigen (SA), live
      antigen (LA) and heat killed antigen (HKA). CFA was most lymphoproliferative when
      assayed in vitro. In an autologous monocyte cytotoxicity assay, soluble protein
      as well as bacterial cells elicited cytolytic responses, however, LA and LLO
      primed monocytes showed a higher cytotoxic effect. The expression of cell surface
      markers of lymphocyte subpopulations was almost identical in experimentally
      infected as well as non-infected calves. SA elicited the highest humoral and DTH
      responses. LLO being a major virulence factor with appreciable humoral as well as
      cellular responses may be used as a candidate antigen to develop a reliable
      diagnostic immunoassay.

PMID- 10063539
TI  - [Acute surgical intestinal diseases].

PMID- 10063540
TI  - [Pathophysiology of ileus].
AB  - OBJECTIVE: To review the endogenous alterations generating critical illness in
      bowel obstruction. DATA SOURCES: Own experimental and clinical investigations and
      relevant articles published in international literature. DATA SYNTHESIS AND
      CONCLUSIONS: Large bowel obstruction is mostly confined to the colon. Passive
      dilatation and increasing luminal pressure might cause local gut wall ischemia
      with impending perforation whereas hypovolemia is not actively induced. Mediators
      are not released. Bacterial translocation occurs with little clinical
      significance. High small bowel obstruction with quantitative reflux predominantly
      causes early and marked hypovolemia and electrolyte disorders. In low small bowel
      obstruction the bowel wall is reacting upon the abundant luminal proliferation of
      gram-negative endobacteria: Induction of mucosal hypersecretion is the main cause
      of hypovolemia. Systemic endotoxinemia beginning with the fourth postobstruction
      day induces a septic inflammatory response encouraging organ failure. Systemic
      prostacyclin liberation in long standing obstruction or following intraoperative
      manipulation might generate cardiopulmonary decompensation.

PMID- 10063541
TI  - [Modern diagnostic strategy in ileus].
AB  - During the last 4 years (11/93-11/97) 330 patients with acute bowel obstruction
      were treated and analysed retrospectively. 80% of the obstructions (n = 265) were
      in the small bowel and 20% (n = 65) in the large bowel localized. Adhesions were
      the main cause in 65.7% (n = 174) of all small bowel obstructions, and one third
      (35.1%, n = 61) of these patients were treated conservatively. In the large
      bowel, however, 37% were caused by obstructing colon carcinoma mainly localized
      in the rectosigmoid region. Mechanical bowel obstruction remains to be one of the
      most common emergencies in general surgery. A successful treatment is based on a
      rapid and correct diagnosis followed by an immediate surgical intervention if
      indicated. There are no reliable clinical, laboratory or radiological signs of
      bowel strangulation available. Preoperative diagnostic examinations should
      confirm bowel obstruction, determine its localization and origin and exclude
      other pathologies. Furthermore, it should help in selecting a patient subgroup
      with small bowel obstruction due to adhesions, which might be treated
      conservatively. Preoperative diagnostic procedures include case history, clinical
      examination, basic laboratory tests and a plain abdominal x-ray. In patients with
      suspected small bowel obstruction due to adhesions without any signs of
      strangulation a contrast medium follow-through study may be indicated. If the
      contrast medium fails to pass into the colon within 5 hours, a surgical
      exploration is recommended. In large bowel obstruction a contrast medium enema, a
      computed tomography or a colonoscopy are valuable diagnostic tools.

PMID- 10063542
TI  - [Surgical therapy of ileus of the small intestine].
AB  - BACKGROUND AND AIMS: Small bowel obstruction is a disease the surgeon frequently
      is confronted with. In the present study the records of the patients (n = 202)
      with mechanical obstruction of the small intestine from the last four years were
      analysed and the results are critically compared with the literature. METHODS: In
      the reported retrospective study the length of patient's history, the cause of
      bowel obstruction, the preoperative examinations performed, the kind of surgical
      intervention and the postoperative management and outcome were investigated.
      RESULTS: The average patient's age was 62 years, the mean preoperative duration
      of symptoms was 6.5 days. 77% of the patients had underwent abdominal surgery
      prior to the obstruction. Conventional x-ray was performed in 92%, gastrographin
      passage in 46% and CT-scan in 23% of the cases. The average length of
      hospitalisation was 12 days. The overall postoperative morbidity was 21%, the
      mortality 2.5%. CONCLUSION: It could be shown that patient's history, clinical
      symptoms and conventional x-rays of the abdomen are sufficient for the indication
      of surgical intervention. In uncertain cases the examination of the passage with
      contrast medium is recommended. The surgical results of small bowel obstruction
      management have significantly improved over the past decades, today's mortality
      is lower than 5%.

PMID- 10063543
TI  - [Surgical therapy of ileus of the large intestine].
AB  - Acute colonic obstruction is a life threatening emergency. In this prospective
      study 69 patients suffering from large bowel obstruction, admitted between
      November 1993 and March 1998 to the University hospital of Bern, were analyzed
      with regard of the performed surgical procedure. The causes of obstruction were
      colorectal carcinomas (38%), other malignancies (19%), volvulus (13%), hernias
      (10%), diverticulitis (7%) and others (13%), 8 benign and 19 malignant lesions
      were surgically treated without colonic resection, the latter by colostomy (13),
      ileostomy (5) or bypass (1). All the other 42 patients had their obstruction
      resected within 24 hours after admission, 24 of them with primary anastomosis and
      18 as a two-staged procedure. However, 9/18 (50%) patients never have had
      restoration of bowel continuity. No three-stage procedure was planned or
      performed. In-hospital mortality was 4/69 (5.8%), all of them after staged
      resections due to non-surgical complications. No anastomotic leakage was
      clinically apparent, neither in one-stage procedures, nor in completed two-stage
      procedures. Median length of total hospital stay in one-stage and two-stage
      procedures was 14 and 30 days, respectively. The advantages of one-stage
      procedures, especially in terms of subtotal colectomy, are discussed on the basis
      of an overview of the literature.

PMID- 10063544
TI  - [Postoperative ileus--early, late or no surgery at all?].
AB  - One third of all relaparotomies are due to early postoperative bowel
      obstructions. Operations on the small bowel and colon are predominant among the
      primary procedures. The main causes of obstructions are adhesions. The symptoms
      of intestinal obstruction in the early postoperative period can be masked by a
      prolonged postoperative ileus. Reoperation of bowel obstruction is easier and
      safer in the first ten postoperative days compared to delayed reintervention
      after unsuccessful conservative treatment. When obstruction occurs after the
      first postoperative week, an initial conservative therapy for 7 to 10 days can be
      successful in over 50%.

PMID- 10063545
TI  - [Idiopathic dilatation of the large intestine (Ogilvie syndrome--acute pseudo
      obstruction)].
AB  - Acute colonic pseudo-obstruction (Ogilvie's syndrome) is characterized by
      abdominal distention and massive colonic dilatation without any mechanical cause
      of obstruction. We have reviewed the records of 57 patients, 36 men and 21 women
      (median age 65.4 y), from 1/1992 to 12/1996, with a colonic pseudo-obstruction,
      defined as dilatation of at least 10 cm on plain abdominal x-ray. 38 cases
      (66.5%) followed surgery or trauma and 19 (33.5%) developed symptoms during
      severe medical illness. 36 cases (63.2%) got i.v. narcotics prior to development
      of Ogilvie's syndrome. 4 patients underwent conservative treatment alone, 53
      patients (93%) had endoscopic decompression with a decompression tube placed in
      49 (86%). Due to 2 failures and 2 complications of endoscopic treatment (one
      ischemic lesion, one perforation; complication rate 3.8%) 4/53 patients had to be
      operated (7.5%). Clinical success of endoscopic treatment was 88.6% at first
      attempt and 92.5% at second attempt. General complications tended to be severe,
      according to the concomitant diseases (morbidity 35%); overall hospital mortality
      was 21% (12/57). In conclusion, we believe that endoscopic decompression and tube
      placement is effective and safe for acute colonic pseudo-obstruction not
      responding to 24 hour conservative treatment.

PMID- 10063546
TI  - [Toxic megacolon: surgical timing important!].
AB  - Toxic megacolon is defined as a fulminant attack of colitis with total or
      segmental dilatation of the colon. Toxic megacolon is mostly a complication of
      nonspecific ulcerative colitis or Crohn's colitis but it may also occur in
      pseudomembranous colitis and other forms of infectious colitis. Toxic dilatation
      of the colon is a sign of transmural acute inflammation in which perforation of
      the colon is impending or may already have occurred. Free perforation means a
      fourfold increase in the mortality of a fulminant attack of colitis. Dilatation
      of the colon is not by itself an indication for immediate operation. The
      dilatation may increase, fluctuate or even disappear, leaving the patient still
      severely ill with toxic colitis requiring immediate surgery. The indication and
      optimal timing of surgical intervention require optimal interdisciplinary
      collaboration between surgeons and gastroenterologists. The procedure of choice
      for surgical treatment of toxic megacolon is colectomy and ileostomy. The
      mortality and morbidity of urgent surgery have been decreased by avoiding rectal
      excision. The rectal stump is either closed as a pelvic Hartmann's pouch or the
      sigmoid remnant is exteriorized as a mucous fistula or closed subcutaneously.
      Progress in intensive therapy and perioperative patient management has relegated
      simple decompression by diverting loop ileostomy and skin-level colostomy as
      advocated by Turnbull et al nearly 30 years ago to the role of an obsolete
      procedure which seems hardly ever preferable to resection of the diseased bowel.

PMID- 10063547
TI  - [What patient needs which stoma?].
AB  - Patients with small bowel obstruction hardly ever need a stoma. Advanced
      peritoneal carcinomatosis (mostly due to colorectal or ovarial cancer) may
      require a proximal palliative fecal diversion. Likewise stomatas for colonic
      ileus became less frequent. The type of the stoma and its necessity depend on the
      patient's condition, on the duration and the cause of the obstruction, i.e. on
      the condition and the damage of the bowel. Terminal sigmoidostomy has its place
      mainly as a part of the Hartmann's procedure treating sigmoid diverticulitis with
      inflammatory pseudotumor, with free perforation and diffuse peritonitis. For
      oncological reasons Hartmann's resection should not be performed for rectal
      cancer--except for very old patients in bad condition. Colonic ileus due to
      colorectal cancer can usually be treated by resection and primary anastomosis. In
      case of delayed ileus it may be better to resect the proximal colon and to
      perform an ileocolostomy to avoid complications. Risky anastomoses due to damaged
      bowel or for patients in bad condition may be protected by a loop-ileostomy or a
      loop transverse colostomy. They are both easy to perform and to close with very
      few complications. Summarizing we may conclude that very few patients really need
      a stoma today--patients showing special risks such as diffuse peritonitis,
      absceding inflammation or damaged bowel as a result of delayed ileus.

PMID- 10063548
TI  - [Conservative and interventional therapy of acute diverticulitis with reference
      to pathophysiology].
AB  - Diverticular disease is most common in the sigmoid colon. Its etiology is
      multifactorial and probably related to low-fiber diets, age dependent changes of
      the colonic wall, hypermotility and myochosis with subsequent increase in
      intraluminal pressure. Acute diverticulitis results from inflammation of a pseudo
      diverticulum. It can progress to pericolitis and perforation with abscess
      formation. Therapy of uncomplicated diverticulitis is a conservative regimen with
      bowel rest and intravenous broad spectrum antibiotics. In subjects with
      complicated diverticulitis, preoperative percutaneous image-guided catheter
      drainage of diverticular macroabscesses is indicated. This aims at resolving
      intra-abdominal sepsis thereby avoiding the need for temporary colostomy and
      multiple-stage surgery. Interval single stage sigmoid resection with primary
      anastomosis should then be performed. Generalized peritonitis, with or without
      evidence of free perforation, should be treated surgically. Long-term cereal
      fiber supplementation and physical activity may prevent complications and
      inflammatory recurrences in diverticular disease.

PMID- 10063549
TI  - [Acute left-sided colonic diverticulitis: diagnosis and surgical indications
      after successful conservative therapy of first time acute diverticulitis].
AB  - PURPOSE: To compare the performances of computed tomography (CT) and water
      soluble contrast enema in the diagnosis and evaluation of the severity of acute
      left colonic diverticulitis, and to propose indications for elective colectomy
      after a first episode of diverticulitis successfully treated medically. PATIENTS
      AND METHODS: Prospective non-randomized study (1986-1997) of 542 patients (290
      women and 252 men with a median age of 64 years) whose final diagnosis was
      confirmed either histologically or radiologically. 465 patients (86%) had a CT,
      439 (81%) had a water soluble contrast enema, and 420 (77%) had both
      examinations. Diverticulitis was considered moderate when CT showed localized
      thickening of colonic wall (> or = 5 mm) and inflammation of pericolic fat and
      water soluble contrast enema showed segmental lumen narrowing and tattered
      mucosa; it was considered severe when abscess and/or extraluminal air/or
      extraluminal contrast were described by CT or the two latter by water soluble
      contrast enema. RESULTS: 410 patients (76%) were treated medically and 132 were
      operated during their hospitalization. Sensitivity of CT for diagnosis of
      diverticulitis was 96%, compared to 87% for water soluble contrast enema (p <
      0.0001). Severe diverticulitis was found in 139 patients (30%) by CT and in 45
      patients (11%) by water soluble contrast enema (p < 0.0001). Age < or = 50 years,
      severe diverticulitis in the initial CT and associated pelvic abscess were found
      to be statistically significant parameters to predict the risk of secondary
      complications after a first episode of diverticulitis successfully treated
      medically. CONCLUSIONS: Performances of CT for diagnosis and evaluation of
      severity of acute diverticulitis are statistically higher than that of water
      soluble contrast enema. We would recommend elective colectomy in patients 50
      years of age or younger with a severe diverticulitis in initial CT, and in all
      patients with an associated pelvic abscess.

PMID- 10063550
TI  - [Surgical therapy of complicated sigmoid diverticulitis: single stage or multi
      stage operation?].
AB  - Surgical tactics for the teatment of complicated diverticulitis are in constant
      evolution and remain a subject of controversy. Amongst 53 patients operated on
      for complicated sigmoid diverticulits over a 10 year period in our hospital, 29
      underwent a Hartmann's procedure (3 Hinchey's stage II, 19 stage III and 7 stage
      IV). Only 11 out of 20 having survived the operation underwent restoration of
      bowel continuity (55%). This experience is in line with the literature. Surgeons
      have become conscious that in reality the colostomy was permanent in a
      significant proportion of patients who were poor candidates for a second
      operation. Therefore there is a tendency to perform as far as possible a
      resection of the sigmoid and a colo-rectal anastomosis in a one-stage procedure.
      In the absence of prospective randomized studies and objective criteria, the
      decision to resect the sigmoid in a one-stage or in a multi-stage procedure is
      based on consensus and clinical judgement.

PMID- 10063551
TI  - [Laparoscopic therapy of diverticulitis].
AB  - The aim of this work is a critical analysis of our results with primary
      laparoscopic resection and anastomosis of the colon for diverticulitis. From
      October 1993 to October 1997, 171 patients with a mean age of 60 years (97 males,
      74 females) have been operated laparoscopically. 95 patients were operated
      electively after many episodes of acute diverticulitis and 76 patients in the
      acute phase, of whom 11 patients presented a colovesical fistula. 6 left
      hemicolectomies and 165 sigmoid resections were performed. Among the sigmoid
      resections 11 patients with simultaneous resection of a colovesical fistula are
      included. The operating time for elective cases was between 130 and 280 minutes
      with a mean of 180 minutes, for acute cases the time was between 75 and 410
      minutes with a mean of 205 minutes. The conversion-rate was 10.5%: problems with
      the instruments n = 2, impossibility to pass the stapler n = 4, severe
      diverticulitis n = 7, iatrogenic lesion of the ureter n = 1, perforation of the
      transverse colon by the trocar n = 1, extended adhesions n = 2, hemorrhage n = 1.
      The morbidity was 10%: abdominal wall hematoma n = 1, intraabdominal hematomas n
      = 2, wound abscesses treated surgically n = 2, conservatively treated
      intraabdominal abscesses n = 2, anastomotic leaks treated with open procedure n =
      2, anastomotic leaks with fistulization n = 4, treated once with laparotomy and 3
      times conservatively, sepsis 3 times treated conservatively. As late
      complications (3.5%) we experienced: a bowel obstruction in 2 patients treated
      with open procedure, herniation at the trocar sites in 3 cases corrected
      surgically and an anastomotic stenosis, that had to be reoperated after an
      unsuccesful dilatation. Analgetic requests have been decreased to the half in
      comparison to the classically operated patients. The mortality: 1 patient (0.6%)
      died due to a fasciitis. The duration of the hospitalisation was 8.4 days in
      average (3-32 days). We can conclude that laparoscopic colon resection should be
      considered as an adequate procedure for the treatment of inflammatory processes.
      A large experience in laparoscopic surgery with continuous training of the
      surgeon is the prerequisite.

PMID- 10063552
TI  - [Peritonitis in diverticulitis: the Bern concept].
AB  - INTRODUCTION: The colon is the most frequent origine for a diffuse peritonitis
      and diverticular perforation is again the most common source of a spontaneous
      secondary peritonitis. This paper first focuses on the treatment of peritonitis
      and secondly on the strategies of source control in peritonitis with special
      emphasis on the tactics (primary anastomosis vs. Hartmann procedure with
      colostomy) for surgical source control. PATIENT AND METHODS: Prospective analysis
      of 404 patients suffering from peritonitis (11/93-2/98), treated with an uniform
      treatment concept including early operation, source control and extensive
      intraoperative lavage (20 to 30 liters) as a standard procedure. Other treatment
      measures were added in special indications "on demand" only. Peritonitis was
      graded with the Mannheim Peritonitis Index (MPI). Tactics of source control in
      peritonitis due to diverticulitis were performed according to "general condition"
      respectively the MPI of the patient. RESULTS: The 404 patients averaged a MPI of
      19 (0-35) in "local" peritonitis and a MPI of 26 (11-43) in "diffuse"
      peritonitis. The colon as a source of peritonitis resulted in MPI of 16 (0-33) in
      the case of "local" respectively 27 (11-43) in "diffuse" peritonitis. From 181
      patients suffering from diverticulitis 144 needed an operation and in 78 (54%)
      peritonitis was present. Fourty-six percent (36) of the patients suffered from
      "local", 54% (42) from "diffuse" peritonitis. Resection with primary anastomosis
      was performed in 26% (20/78) whereas in 74% (58/78) of the patients a Hartmann
      procedure with colostomy was performed. The correlating MPI was 16 (0-28) vs. 23
      (16-27) respectively. The analysis of complications and mortality based on the
      MPI showed a decent discrimination potential for primary anastomosis vs Hartmann
      procedure: morbidity 35% vs. 41%; reoperation 5% vs. 5%; mortality 0% vs. 14%.
      CONCLUSION: In case of peritonitis due to diverticulitis the treatment of
      peritonitis comes first. Thanks to advances in intensive care and improved anti
      inflammatory care, a more conservative surgical concept nowadays is accepted. In
      the case of diverticulitis the MPI is helpful to choose between primary
      anastomosis vs. Hartmann procedure with colostomy as source control. The MPI
      includes the "general condition" of the patient into the tactical decision how to
      attain source control.

PMID- 10063553
TI  - [Lower gastrointestinal hemorrhage: etiologic assessment and surgical concept].
AB  - Due to its occurence in patients at higher ages with comorbidities, lower
      gastrointestinal bleeding remains a challenge in terms of diagnostic and
      therapeutic strategies. In this series (1994-1997, n = 40) the source of bleeding
      was in the upper gastrointestinal tract in 38% and in the lower gastrointestinal
      tract in 62%. The source of bleeding could be localized in 58%. Bleeding stopped
      spontaneously in 40% of all patients but 60% required intervention (54%
      radiologic or endoscopic intervention, 46% surgery). Segmental resection was the
      procedure most frequently employed (8/11 patients), 3 patients underwent a
      subtotal colectomy. In-hospital mortality and surgical morbidity were 0/11 each.
      Following a staged diagnostic approach and segmental surgical resection, lower
      gastrointestinal bleeding can be treated with a low morbidity, mortality and a
      low rebleeding rate.

PMID- 10063554
TI  - [Surgical therapy of mesenteric infarct].
AB  - Acute mesenteric infarction represents less than 1-2% of all surgical emergencies
      but is responsible for many lethal events. A successful management requires very
      efficient diagnostic and therapeutic measures. Cases with established bowel
      infarction are associated with a mortality rate of 80-90% since years. In the
      last 10 years some hospitals offering an aggressive pre-, per- and postoperative
      multimodal therapy could reduce the mortality in selected series to 50-60%. One
      of the most important factors to reduce the mortality is beneath early diagnosis
      the emergency angiography and the angiography-associated treatment like
      intraarterial application of vasodilators, even in occlusive forms of mesenteric
      infarction. But this concept is seldom applicable to small hospitals because of
      the partially lacking availability of angiography. We present a concept of
      treatment taking into account this fact. Generous indication for emergency
      laparotomy in patients suspect of acute mesenteric ischemia is the central pillar
      of our concept. We also plea for a very restraint indication in biologically old
      multimorbid patients presenting a sum of negative prognostic factors and consider
      in these cases the reluctant attitude as an ethically and medically positive
      behaviour.

PMID- 10063555
TI  - [Mesenteric infarct--when is the vascular surgeon needed?].
AB  - The treatment of acute mesenteric infarction is a therpeutical challenge. The
      mortality rate of these, mainly beyond 70 year old patients has remained
      extraordinary high despite diagnostic and therapeutic efforts and progress in
      intensive care medicine. Additionally to the initial hypoxaemia of the bowel a
      more severe tissue damage is induced via the "reperfusion injury", with increase
      of the vital risk. Besides the detection of occlusive vascular lesions of
      different etiology, which have to be treated immediately, "non occlusive
      mesenteric ischemia" can be identified. Visceral biplane angiography is the
      diagnostic tool of choice, giving basic informations on concomitant lesions, for
      a rational vascular surgical intervention and additionally the opportunity to
      administer vasoactive drugs. Despite increasing treatment modalities influencing
      the severity of the "reperfusion injury" the most important criteria for the
      patients' survival is the early diagnosis and immediate treatment. Therefore,
      close cooperation of general practitioners, internists, radiologists,
      angiologists, general surgeons and vascular surgeons is required. The support of
      a vascular surgeon is necessary for complex arterial reconstructions as success
      and patency rate are significantly influenced by experience. Reocclusion and
      "redo"-surgery increase the risk substantially.

PMID- 10063556
TI  - [Ischemic colitis and mesenteric ischemia after abdominal aortic reconstruction].
AB  - Ischemic colitis is quite a rare condition, which can be subdivided into two
      categories, a so-called occlusive form as a complication of various vascular
      diseases, and a non-occlusive form caused by exogenous administration of drugs,
      or i.e. higher cocentrations of various endotoxines or cytokines. Besides the
      most serious cases with transmural ischemia, needing operation and resection,
      over 50% of all cases suffer from non-transmural or mucosal ischemia which can be
      treated conservatively. These cases usually show a rather favourable outcome. A
      part of these patients will suffer from bowel stenosis or strictures later on and
      may need secondary resections. Ischemic colitis following aorto-iliac
      reconstructive surgery is a rare but well known complication. Although it should
      be suspected much more frequently, only 1 to 2% of the patients will present a
      condition of clinical importance. The complication is more frequent in patients
      who undergo surgery as an emergency, especially reconstruction for aneurysmal
      disease, and it is less frequent in patients who undergo aorto-iliac
      reconstruction for occlusive disease; probably because the latter have already
      developed collateral vessels in the visceral area. A preoperative evaluation of
      this specific risk is rarely possible by angiography. Intraoperative strong
      pulsating backflow from the inferior mesenteric artery is considered as a quite
      reliable prognostic factor for a sufficient mesenteric circulation. Measurement
      of inferior mesenteric stump pressure, fluoresceine instillation and doppler
      ultrasound have been proposed as more reliable predictive elements. Wherever
      mesenteric circulation seems to be doubtful, inferior mesenteric replantation is
      advisable. In the postoperative course, a thorough clinical surveillance and
      probably systematic sigmoidoscopy especially on patients with prolonged
      intubation in strongly advisable in order to detect ischemic lesions in an early
      stage. Early operations on transmural lesions will help to improve this otherwise
      very serious and life threatening complication.

PMID- 10063557
TI  - [Laparoscopic transabdominal adrenalectomy].
AB  - Adrenalectomy is an operation, which is particularly suitable for minimally
      invasive techniques. In several surgical departments with special interest in
      endocrine disorders laparoscopic adrenalectomy has become the procedure of choice
      in the surgical treatment of benign adrenal lesions. In transabdominal
      laparoscopic adrenalectomy the adrenal region is exposed by mobilizing the liver
      or the spleen respectively. The inferior vena cava and the left renal vein are
      the most important landmarks for further dissection and orientation. Different
      retroperitoneoscopic approaches have been described besides the transperitoneal
      techniques.

PMID- 10063558
TI  - [Technique of total extraperitoneal endoscopic hernioplasty of the inguinal
      canal].
AB  - The current end stage in the development of endoscopic treatment of inguinal
      hernia involves the introduction of a patch into the extraperitoneal space. This
      may be done via a transabdominal approach (TAPP) or via a total extraperitoneal
      approach (TEP). The present article describes the TEP technique in detail. In
      addition to dealing with the ideal case, the authors also discuss the procedure
      in relation to all know forms of hernia. Furthermore, they provide the reader
      with suggestions on how to deal with intraoperative technical problems and how to
      avoid recurrences.

PMID- 10063559
TI  - [Recommendations on contents of medical reports in rectal carcinoma: III:
      Radiotherapy report and final report of chemotherapy. Orientation aids in
      interdisciplinary patient management].

PMID- 10063560
TI  - [Classifications in trauma surgery (1)].

PMID- 10063561
TI  - [Significance of surgical therapy of breast carcinoma for the surgery specialty].

PMID- 10063562
TI  - [Molecular biology of breast carcinoma. Current diagnostic, therapeutic and
      prognostic aspects].
AB  - There has been a huge progress in our understanding of the genetic mechanisms
      involved in the development of breast cancer. The clinical consequences are
      however still small. The most important theoretical models for future clinical
      investigation, as well as the practical consequences of the already known facts
      are discussed.

PMID- 10063563
TI  - [Differential atypical ductal hyperplasia/DCIS/invasive carcinoma diagnosis and
      significance of micrometastases].
AB  - During the last years the increasing knowledge of preliminary stages of breast
      cancer has substantially contributed to the understanding and therapy of this
      disease. The definition and classification are shortly discussed.

PMID- 10063564
TI  - [Steroid hormone receptor status and other immunohistochemical prognostic markers
      in benign and malignant diseases of the breast].
AB  - In addition to classical morphological prognosis factors of breast carcinoma
      (pTNM stage, tumor grading, histological typing), many other immunohistochemical
      markers of different prognostic value exist.--The comparative estrogen (ER) and
      progesterone receptor (PR) analysis of normal and pathological breast tissue
      showed a gradually inverse biological correlation between the decrease of ER+PR+
      and the increase of ER-PR-frequency from benign breast changes to noninvasive and
      invasive breast carcinomas. In benign breast epithelium, ER+PR+ and ER-PR+ might
      be regarded as low-risk phenotype, whereas ER+PR- and ER-PR- could be estimated
      as high-risk phenotype in view of a later dedifferentiation and possible
      malignization.--During carcinogenesis, the initial loss of epithelial growth
      factor receptor (EGF-R) as well as its later neoexpression could be regarded as a
      progression maker.--The proliferation rate (Ki67) in breast cancer significantly
      correlates with increasing grading and apoptosis rate, whereas the expression of
      bcl-2-protooncogene is inverse to increasing grading. As for the prognostic value
      of the single factors, it is supposed that they mostly might represent "one piece
      of a larger puzzle" [13].

PMID- 10063565
TI  - [Possibilities and limits of diagnostic frozen section in breast carcinoma].
AB  - A short overview is given demonstrating the possibilities and limits of the
      frozen section technique in mammary carcinoma. The accuracy of this method in
      diagnostic pathology of the mammary gland is up to 97% when applied by
      experienced pathologists. In case of breast cancer it may be difficult to
      determine the maximum of tumor size and the minimum tumor-free distance to the
      resection margin which are significant for a breast-conserving operation. There
      are further limits when an atypical ductal hyperplasia (ADH) should be
      differentiated from a ductal carcinoma in situ (DCIS) and when in case of DCIS
      microinvasion is to be proven. Nevertheless, intraoperative frozen section
      technique is unrenunciable for breast cancer surgery. Mistakes can be avoided in
      most of the cases, if surgeon and pathologist will closely cooperate and if both
      are fully aware of the limitations of the method.

PMID- 10063566
TI  - [Changes in TNM stages in breast carcinoma over the course of 20 years].
AB  - The TNM-classification of the breast cancer was analysed in a period of time from
      20 years in our hospital. We found a permanent increase of T1-stage. The change
      of this stage was investigated in combination with the introduction of the
      mammography and the possibility to mark mammographic suspect lesions nonpalpable
      tumors.

PMID- 10063567
TI  - [Introduction of studies by the German Breast Center Study Group (GBSG)].
AB  - The GBSG is actually running two studies on breast cancer therapy: GBSG-5
      addresses the necessity of radiotherapy following tumor removal, in breast
      preserving treatment of pT1N0M0 G1 breast cancer. The other question to be
      answered in a randomised 2- by 2-design is related to the replacement of
      radiotherapy by a 5-year treatment with tamoxifen. Up till now, 341 patients have
      been randomised. 200 more patients are needed for a valid study evaluation. GBSG
      6 will be activated in fall of this year. It should answer the question whether
      the addition of systemic therapy to the local treatment of isolated locoregional
      recurrence will prolong time to further relapse as well as overall survival.
      According to a prognostic profile derived drom previous studies patients will be
      randomly allocated to more or less intensive treatment with chemo- and/or hormone
      therapy.

PMID- 10063568
TI  - [Therapy studies of the Austrian Breast Cancer Group (ABC)].
AB  - The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating
      centers in Austria has randomized more than 5800 patients in 11 randomized trials
      since 1984. At present, roughly 30% of all patients with the diagnosis primary
      breast cancer are accrued in protocols throughout the country. Due to specific
      activities, the breast conservation rate raised from an initial 20% to more than
      60% in the last years. Multicenter trials are not only the basis for progress in
      medicine but also tools for quality control and quality improvement.

PMID- 10063569
TI  - [Value of mammography and ultrasound in diagnosis of breast carcinoma].
AB  - The assessment of the value of mammography and ultrasound studies of the breast
      was the aim of this work. Mammography has consistently demonstrated its value as
      a good screening method, but also in the differentiation between several
      diagnoses. The sensitivity of the mammography is high with 85% to 90%. The
      specificity should be considered critically and can't be used in every case. But
      the use of additional methods of the mammography sometimes arrives more
      information. Therefore the mammography is the basic method for detection of early
      clinically occult cancer. Advantages of ultrasound are the better differentiation
      of cysts from solid lesions and the dissolution of dense breast masses in the
      mammography. However the mammary ultrasonography has more limitations than
      mammography. Some different kinds and materials for improving ultrasound are high
      resolution or colour Doppler ultrasound and the using of ultrasound contrast
      agent. At present mammasonography seems to be the most important additional
      method behind mammography.

PMID- 10063570
TI  - [Combination of mammography with automated ultrasound (Sono-X) in routine
      diagnosis?].
AB  - A new technique for breast imaging is presented. This technique combines
      radiographic mammography directly with automated ultrasound. The combined
      examination, which is performed without decompression of the breast, yields the
      conventional mammography films as well as a complete set of B-mode scans and
      ultrasound projections. These can be geometrically matched with each other in a
      definitive manner. A prototype of the device was first used in a pilot study of
      50 patients followed by a study of an additional 450 patients with a total of 492
      breast lesions, of which 269 were confirmed by histology or cytology. The results
      show that X-ray and ultrasound are complementary in the detection of cancer. The
      use of an experimental mode of image interpretation for combined mammography and
      automated ultrasound reduced the number of mammographically suspicious findings
      that ultimately turned out to be benign. These results were also confirmed in two
      blind studies including a total of 160 histologically or cytologically confirmed
      lesions and 40 cases without lesions. With further technical advancement of the
      technique aimed at rapid and easy application and confirmation of the results
      obtained so far, the combination of mammography and automated ultrasound might be
      introduced into a routine clinical setting.

PMID- 10063571
TI  - [Optimal use of MRI mammography from the economic viewpoint].
AB  - With the introduction of the contrast agent gadolinum DTPA there were hopes that
      "MRM" would prove to be the investigatory technique that would largely solve the
      problems of breast diagnostics. However, after the early years of acceptance, the
      new method of investigation became a subject of controversy. Nonetheless, MRM
      today occupies a recognized place in diagnostics for certain indications. It is
      still true, however, that reliable use of this procedure requires a great deal of
      experience, since there is a relatively large area of overlap between benign and
      malignant tumors. Further, the costs are significantly higher than those for
      conventional methods of investigation. New studies that have been conducted at
      the Charite, Campus Virchow Medical Center in Berlin, suggest that, if one takes
      the relevant indications into account, MRM can be economic and contribute
      significantly to cost reduction. Application of a newly developed software
      package has shown that the good discrimination in a suspect area resulting from
      contrast agent enhancement makes possible a reliable differentiation between
      malignant and benign tissue changes. A further result was that, when certain
      boundary conditions are satisfied, a contrast agent bolus of 0.1 mmol/kg BW is
      sufficient, making a double dose (0.2 mmol/kg BW) unnecessary.

PMID- 10063572
TI  - Results of the European multicenter study of radionuclide mammography with Tc-99m
      MIBI.
AB  - In the European multicenter trial 246 female patients with suspicious
      mammographic result and/or breast mass were studied. In 253 lesions (195
      palpable, 58 non-palpable) 165 malignant and 88 benign results were obtained
      histologically. All scans were evaluated centrally and institutionally. Central
      evaluation (per lesion) resulted in a sensitivity of 71% and a specificity of
      69%. For palpable lesions, sensitivity was 83% in the central read and 91% in the
      institutional read. No difference was observed between invasive ductal and
      invasive lobular carcinoma. X-ray density had no influence on scintigraphic
      sensitivity. Sensitivity and specificity of mammography were 91% and 42%,
      respectively.

PMID- 10063573
TI  - [Initial experiences with radionuclide mammography at the Cottbus Carl-Thiem
      Clinic].
AB  - In the diagnosis of breast cancer, noninvasive methods are need in order to
      detect early stages of this disease. These methods have to have a high
      specificity in order to discriminate malignant and benign lesions. The
      scintimammography with 99mTc-MIBI might be such a new method. With this
      examination the early diagnosis of breast cancer might be improved and may reduce
      the need for diagnostic biopsies. The aim of our examinations was to get first
      experiences in comparison with the histological results. The histological results
      were considered to be the reference method. 25 scintigrafical examinations were
      evaluated, performed from August 1997 to January 1998. The scintigrafical results
      were recorded qualitative-visually with a score from 1 to 4. The histological
      results were received within 1 week after realization of the scintigrafical
      examination. 22 scintigrafical examinations were evaluated correctly. Of 16
      benign lesions 14 were evaluated as true negative and 2 as false positive
      (fibroadenoma, haematoma). Of the 9 breast carcinomas 8 were evaluated as true
      positive and 1 false negative (lobular carcinoma in situ). In the case of
      unselected patients, low numbers of examinations and a diameter of the smallest
      carcinoma from 1.4 cm a sensitivity of 89% and a specificity of 88% has been
      observed. Our sensitivity and specificity was in the range of the current
      international scintimammography-studies. Statements about little breast
      carcinomas (diameter < 1 cm) are not yet available, because such patients were
      not examined. The scintimammography is not a screening test. It renders no
      additional information in the case of clear clinical results and/or clear
      mammography. Therefore useful indications have to be defined in subsequent
      scintimammography studies. Possible indications are: palpable breast lesions,
      which appear normal in mammography, uncertain results in mammography without
      palpable result and in the follow up of operations of breast cancer without
      mastectomy. It might be interesting to compare in the future new radiological
      methods and magnet resonance imaging and positron-emission tomography in the
      diagnosis of breast cancer with the represented conventional method.

PMID- 10063574
TI  - [Positron emission tomography (PET) in diagnosis of breast carcinoma].
AB  - Position emission tomography (PET) offers new opportunities in the non-invasive
      diagnosis and therapy monitoring of breast cancer. So far, PET with the glucose
      analogue fluorodeoxyglucose is investigated best, especially in diagnosing the
      primary tumour and in staging axillary lymph nodes. The validity of the method in
      staging distant metastases and monitoring therapy is also being investigated. At
      the moment, few data is available on PET with C-11-methionin as well as on PET
      with more specific radiopharmaceuticals like I-124-labelled monoclonal antibodies
      and F-18-labelled estrogen receptor ligands. This short review presents the state
      of the art of PET in the diagnostics and therapy monitoring of breast cancer.

PMID- 10063575
TI  - [The ABBI system as a possibility for evaluating non-palpable lesions].
AB  - For non-palpable lesions detected radiographically alone, lumpectomy after needle
      localization is currently performed. Specimen radiography provides an indirect
      proof of complete excision of the mammographic abnormality. Up to now,
      intraoperative mammography of the operated breast has not been possible. Digital
      intraoperative mammography is now possible with the ABBI-system, which will be
      introduced in this article. In a pilot study, we have investigated, whether it is
      possible to excise small carcinomas with the ABBI stereotactic biopsy device
      (maximum diameter 20 mm) without compromising breast conserving therapy. In a
      prospective study, 69 patients were diagnosed or treated using the ABBI-system.
      In all 60 patients with a primary lesion, a cylindrical excision was performed.
      Of these, 11 invasive and 5 intraductal carcinomas were diagnosed. 7 of the
      invasive and 2 of the intraductal cancers were treated with breast conserving
      surgery. In 9 cases, an in-breast recurrence was suspected. In 7 of these a
      cylindrical excision was performed. One invasive and 3 intraductal carcinomas
      were found and mastectomy was performed in these four patients. In two patients
      with the suspicion of an in-breast recurrence, the ABBI-system was used to
      perform a core-needle biopsy. In one patient, the biopsy finding was positive and
      mastectomy was performed. Patients with lesions close to the chest wall are not
      suited for the ABBI-system. The postoperative course was uneventful in all cases,
      the cosmetic result after breast-conserving therapy was very good. The advantages
      of this new method consist in the reliable stereotactic localization of
      suspicious lesions and in the fast intraoperative imaging.

PMID- 10063576
TI  - [Minimally invasive stereotactic breast biopsy with the "mammotome". Methodology
      and personal experiences].
AB  - A new method of minimally invasive breast biopsy is described. The system
      components are a stereotactic biopsy table, a digital mammography, an automatic,
      computer-assisted needle positioning device and a new vacuum core biopsy needle.
      With this needle multiple core biopsies can be collected through a single
      insertion. The procedure was performed as outpatient status and was very well
      tolerated by the patients. Our experiences with this method are very promising.
      The method will reduce the relation of benign to malignant histology in open
      biopsies.

PMID- 10063577
TI  - [New methods for minimal invasive assessment of uncertain mammography and MRI
      tomography findings].
AB  - Results of 3 minimal invasive techniques for breast biopsy of clinically occult
      lesion are presented. 1. Mammographically guided Site-Select biopsies allow
      removal of tissue in one piece using a large diameter core biopsy instrument
      (similar to the ABBI-principle). However the overlying subcutaneous tissue is
      saved. No technical problems occurred in 13/13 diagnostic biopsies. Complete
      removal was, however, only possible in 2/4 tumors < 1 cm due to tissue shift
      during insertion of the instrument. 2. Mammographically guided vacuum biopsy also
      allows contiguous removal of areas of 1.2-1.8 cm diameter, while blood is
      suctioned out, as well. 3 stereotaxic miscalculations were immediately
      recognized. Diagnostic accuracy in 405 biopsies so far is 100%. The examination
      was very well tolerated by the patients. 3. By means of a specially developed
      biopsy coil and vacuum biopsy percutaneous in- or excisional biopsy of enhancing
      lesions visible by MRI alone has been realized by us for the first time. 24/25
      diagnoses are definitely representative--as proven by lack of enhancement after
      biopsy. One diagnosis, which was uncertain due to overlying blood, is being
      followed. Minimal invasive methods may open up new perspectives.

PMID- 10063578
TI  - [Sentinel lymph nodes in breast carcinoma].
AB  - Aim of the experiment is to select patients with positive axillary lymph nodes by
      means of the sentinel lymph node concept. In this way all other patients who
      would not benefit from a lymph node dissection are spared from this procedure and
      its morbidity. Till now the sentinel lymphadenectomy is, however, still an
      experimental technic with yet unproven utility.

PMID- 10063579
TI  - [Sentinel lymph node detection in patients with breast carcinoma].
AB  - Sentinel node detection enables the definition of the most relevant draining
      lymph node of a tumor. We analysed 123 patients with breast cancer according to
      this method. A preoperative lymphoscintigraphy was performed 17 hours after a
      peritumoral application of 0.5 ml 99mTC-Nanokoll. The sentinel node was
      identified by means of a gammaprobe in 75 of 89 patients with pT1- and pT2-tumors
      and in 11 of 17 patients with pT3-4 tumors respectively. The results of
      histological investigation of the sentinel node in comparison to all other
      axillary nodes following dissection were correlated. In the pT1-2 group the
      accuracy of correlative findings was rather high (96%). In patients with pT3- and
      pT4-tumors the lymph node status was predictable only in 7 patients. Therefore
      sentinel node biopsy may serve as a tool for individualization of axillary
      dissection especially in pT1-2 breast cancer patients.

PMID- 10063580
TI  - [Surgical strategies in treatment of breast carcinoma].
AB  - The surgical strategies in the treatment of operable breast cancer have changed
      basically within the last decades. Today the therapy of breast cancer is
      indicated by the individualization of the procedure in which the extent of the
      operative intervention is determined in first line in dependence of the clinical
      and histopathological results and the wishes of the patients. The current
      surgical strategies are indicated by a further reduction of radicalness in the
      operative procedure and a patient obtained strategy adapted to the individual
      risk. Goals of the reduction of the radicalness are discussed at the example of
      the extend of minimal tumor free margins and the technique of the "sentinel lymph
      node detection". The use of Van-Nuys classification is described as an example
      for an individual risc adapted strategy in the surgical treatment of breast
      cancer. Furthermore is discussed the significance of the extensive intraductal
      component, of lymphatic and blood vessel invasion and the patient's age for
      estimating the risk of of local recurrence after breast preserving therapy.
      Besides of all efforts there are still limits in reducing surgical radicalness of
      the therapy of breast cancer. That has to be taken into account in an adequate
      therapeutical concept.

PMID- 10063581
TI  - [Surgical procedure in primary and metastatic breast carcinoma].
AB  - We know that breast cancer is already a systemic disease in the majority of
      patients at the time it is first diagnosed, requiring an interdisciplinary
      treatment concept. This fact has changed the surgical treatment approach of
      primary breast cancer which currently follows the principle: "As much as
      necessary, as little as possible". Improved early detection of breast carcinomas
      allows the treatment of a majority of early stage breast cancer patients with
      breast-conservation surgery, followed by irradiation except for a few
      contraindications. Although survival is not significantly different for patients
      who undergo breast conservation surgery plus irradiation than for those having
      modified radical mastectomy, the pattern and prognostic value of locoregional
      failure are different. Locoregional failure after breast conservation requires
      mastectomy, thoracic wall recurrence will be treated by (en-bloc) resection and
      irradiation. Following rigorous selection criteria and indications, surgical
      resection of distant metastases to the liver, lung or brain can improve the
      quality of life and prolong survival, it should therefore be taken into
      consideration in individual cases. Since the two breast cancer susceptibility
      genes, BRCA1 and BRCA2, have been detected, high-risk patients should be offered
      the possibility of genetic counseling and genetic testing. Based on our present
      knowledge, the surgical approaches for BRCA1 or BRCA2 mutation carriers with
      breast cancer remain unchanged. There are some indications that molecular tumor
      parameters can be used to identify a subgroup of primary breast cancer patients
      who are characterized by a poorer prognosis. The results achieved in our own
      patients add further evidence in favor of this theory.

PMID- 10063582
TI  - [The plastic surgery concept as an important prerequisite in operative treatment
      of breast carcinoma].
AB  - Between 1992 and 1997, 424 female patients were treated for primary breast cancer
      at the Department of Surgery of the Carl-Thiem-Klinikum in Cottbus. The
      percentage of breast conserving surgical methods hat increased from 10% (1992)
      30% (1997). The rate of local recurrence after breast conserving surgery was 8%
      in 1997. We found a ratio of breast cancer surgery to diagnostic biopsies of 1:1,
      1 in 1992 and of 1:2,1 in 1997. After the introduction of reconstructive breast
      surgery in 1997 we carried out 3 immediate reconstructions with endoprosthesis
      and 7 cases with myocutaneous flapping. Our own concept of plastic surgery as
      well as indications for breast conserving therapy will be demonstrated and
      discussed.

PMID- 10063583
TI  - [Prognosis of breast carcinoma after Rotter-Halsted operation. 10-year outcome in
      240 patients].
AB  - Between 1974 and 1987 240 patients with cancer of the breast were operated upon.
      The course of all patients was followed over a period of 10 to 24 years. 87
      patients died from breast cancer, 15 from other malignancies, and 74 from other
      unrelated diseases. 64 patients are surviving until now.

PMID- 10063584
TI  - [Breast carcinoma in routine surgery. Challenges and reality].
AB  - This is a brief comment on results in the common surgical treatment of breast
      cancer. Based on guiding-lines given by the surgical congress 1985 the
      decentralized treatment routine as it is common today has been analysed and its
      results have been applied to our regional structures. Under the premises of
      standardized diagnosis as well as surgical and postoperative treatment the
      decentralized treatment of breast cancer is still supported and considered
      useful. Main critical point in the whole therapy concept is the postoperative
      treatment, especially the adjuvant therapy. Looking for future solutions it seems
      to be more effective to reduce the amount of surgical facilities for the benefit
      of profiling the remaining ones. This could be applicable for the treatment of
      other diseases as well. The improvements that would result from this conceptional
      concentration would be profitable as well for the patients as for the surgeons.

PMID- 10063585
TI  - [Surgical procedures in therapy of breast carcinoma with reference to the value
      of axillary endoscopy techniques].
AB  - During the last decades the surgical treatment of breast cancer has been
      dramatically changed. Today breast conservative treatment represents a
      therapeutic option applicable to nearly 70% of the women. In contrast to this,
      the technic of axillary dissection remained unchanged. Suzanne et al. proposed an
      axilloscopic technic to reduce this morbidity. The sometimes unacceptable low
      lymph node count in the specimen induced us to modify this procedure. In the
      future the sentinel lymph node concept perhaps offers the possibility to select
      NO-patients and to spare the axillary dissection completely to this sub-group.

PMID- 10063586
TI  - [Endoscopic axilla dissection in invasive breast carcinoma. Initial experiences
      with a new technique].
AB  - The presence or absence of involved axillary lymph nodes is the single best
      predictor of survival of breast cancer, and important treatment decisions are
      based on it. For staging purpose as well as for local control a level I and II
      dissection is recommended. In order to lower the morbidity of axillary lymph node
      dissection less invasive treatment modalities have been evaluated. Beside the
      sentinel lymph node biopsy another new method is discussed: the endoscopic
      axillary lymph node dissection. After liposuction of the axillary fat the lymph
      nodes of level I and II are removed by endoscopy. With this technique enough
      lymph node can be removed which allows a sufficient staging as well as local
      control. This technique is not to be recommended for general use unless long term
      results have proven its value.

PMID- 10063587
TI  - [Therapy concept in phyllodes tumors of the breast].
AB  - The data of 22 women with a phyllode tumor of breast operated in our department
      from 1980 to 1997 were analysed. 11 benign, 7 borderline and 7 malign phyllode
      tumors were found in accordance to WHO-classification. In conclusion diameter of
      tumor is a relevant prognostic factor beside histologic classification. Therefore
      local excision is recommended for benign and borderline phyllode tumors smaller
      than 5 cm. A safety distance of 1 cm is claimed. Benign or borderline lesions
      greater than 5 cm and all malign require a simple mastectomy. Only recurrence
      smaller than 5 cm after excision of benign and borderline phyllode tumor should
      excised once more. Metastasis have to be cured by surgical therapy.

PMID- 10063588
TI  - [Breast reconstruction with the free microvascular abdominal flap. Accessory
      reconstruction or gold standard?].
AB  - Long time results of breast reconstruction after ablative surgery with skin
      expander and prothesis is perceived as unsatisfactory by most patients. Breast
      reconstruction with autologous tissue however is connected with a high technical
      expenditure and especially in the case of the free TRAM-flap connected with the
      risk of total loss of the transplanted tissue. In view of the total effort in
      secondary interventions, and reduction of the collateral side, the autologous
      reconstruction proves to need less time, resources and hospital admissions
      already after a 2 year period. Minor revisions mark the long time course of
      breast reconstruction with expander and prothesis. Judging by the patients
      themselves they prefer the reconstruction with autologous tissue and in this
      subgroup microsurgical reconstruction yields the better results to the patient.
      Review shows that the microsurgical procedure allows the transfer of larger
      volumes and better positioning of the breast including a physiologic breast
      ptosis. TRAM-flap donorsites seem to yield equal results in dynamic as well as
      static exercise regardless of the microsurgical or pedicled technique. The review
      of our own 48 patients with 50 TRAM-flaps coincide with the review of the current
      literature.

PMID- 10063589
TI  - [Integration of plastic surgery-esthetic aspects in surgical therapy of breast
      carcinoma].
AB  - Within the last 20 years there was an important change in the operative treatment
      of breast cancer. New considerations on the tumor biology resulted to the
      conviction, that the operative radicality does not affect the overall survival
      rate. This was in addition the birth hour of the breast conserving surgery and of
      the efforts of reconstructive procedures of the female breast. Muscle flap
      procedures got more and more importance in clinical practice. This paper gives an
      overview on our concept of breast conserving therapy and primary reconstruction
      in case of carcinoma of the breast, which is based on oncoplastic aspects. With
      consideration this model we are enabled to improve the cosmetic results even in
      cases with larger tumors.

PMID- 10063590
TI  - [Breast reconstruction: autologous tissue versus implant].
AB  - Modified radical mastectomy remains the standard for treatment of breast cancer.
      Women faced with the diagnosis of breast cancer often find it difficult to cope
      with the arousing emotions. Fear of death or cancer recurrence and a perceived
      loss of femininity often coexists with the desire for a return to normality and
      wholeness. For women seeking breast reconstruction various techniques have been
      developed. Two different ways for breast reconstruction have become a standard.
      One way is the reconstruction by tissue expansion or transposing locally
      available tissue with the use of implants. The other way is the reconstruction of
      the breast without using any implants with the Latissimus dorsi flap or the TRAM
      flap. METHODS: We performed 291 breast reconstructions. In 125 women available
      tissue and an implant was used. The Latissimus dorsi flap was used in 57 cases
      and 109 TRAM flaps either pedicled or as a microvascular flap were performed.
      RESULTS: Using expanders we found a perforation of the device in 2 cases. After
      using implants there were capsular contracture in 2 cases and in 1 case we had an
      infection. Using autologous tissue we had 2 partial flap necrosis, 4 hematomas,
      and 4 prolonged healings. There was no complete flap necrosis. DISCUSSION: Breast
      reconstruction using autologous tissue i.e. the TRAM flap is supposed to be a
      standard technique. Microsurgical transplantation of the TRAM flap shows almost
      no morbidity of the donor site area. Autologous tissue follows the changes of the
      body like weight gain or reduction to a certain extend and shows neither capsular
      contracture nor other implant associated side effects. Women get the impression
      that the TRAM flap is like soft tissue to the touch and not like a foreign body.
      The aesthetic results were in all cases superior sometimes needing minor
      secondary correction and mostly shaping of the nippel-areola complex. All
      patients were pleased with the result.

PMID- 10063591
TI  - [Oncoplastic variations in surgical treatment of pT2 breast carcinoma].
AB  - We retrospectively reviewed 156 cases with pT2-breast cancer (tumorsize 2-5 cm)
      who where treated between 1.1.1993 and 1.10.1997 our hospital. We evaluated in
      how many cases and with the usage of which techniques we where able to perform
      breast-conserving surgery. With this tumor size we almost exclusively used
      oncoplastic mammoplasties and flaptechniques which where shaped individually
      depending on the modality of tumorspread, the size of the breast and the personal
      wishes of the patient. With this method of altering the treatment according to
      the needs of the individual depending on the tumor size and tumor location and
      including adjuvant therapies as radiotherapy and chemotherapy, we where able to
      save the breast in 106 (67.9%) of all patients with pT2-tumors. CONCLUSION: At
      our hospital we are able to offer many of the patients with pT2-breast cancer,
      who are usually still often treated with ablation of the mamma, breast-conserving
      procedures. We do this with the help of individualized patient-orientated and
      tumor-adaptive treatment plans and linked with the departments of radiotherapy
      and chemotherapy.

PMID- 10063592
TI  - [Breast reconstruction-plasty. A modification of the Strombeck-Wise technique].
AB  - We report about 7 patients with an modification of Strombeck-Wise-technique in
      reduction mammoplasty. The average weight of reduced breast tissue was about 650
      g per side. The experience of this method shows an procedure without
      complications, with good plastic results and an successful intraoperative
      symmetry adaptation.

PMID- 10063593
TI  - [Surgical therapy of chest wall infiltrating local recurrence of breast
      carcinoma].
AB  - Chest wall resection and--reconstruction for malignant tumors have to fulfill
      oncological, functional and cosmetic demands. We report on 19 operated patients
      with chest wall recurrence or metastasis from breast cancer. Resection included
      excision of the thoracic shield (n = 14), additional partial resection of breast
      bone (n = 5) and of clavicle (n = 1). Chest wall stability was achieved by PTFE
      patches and lyophilized bone, soft tissue reconstruction was performed by
      myocutaneous flaps. Resection rate was 95%, morbidity rate was 23%, we saw no in
      hospital deaths. 1-year-survival was 95%.

PMID- 10063594
TI  - [Thoracic surgery relevant indications for adjuvant and/or palliative measures in
      breast carcinoma].
AB  - Metastatic lesions of breast cancer represent rare indications for operation in
      thoracic surgery. Only in case of persistent malignant pleural effusions or in
      case of tumour progress despite all other available therapy modalities thoracic
      surgery can be indicated. Over a period of 5 years between 1993 and 1997 53
      patients with metastatic breast cancer were treated in our institution. 36 pts.
      suffered from persistent pleural effusions, 13 pts. had pulmonary metastases and
      4 pts. had metastases involving the chest wall. In all these patients the disease
      could not be controlled by conservative measures. Our experiences are the
      following: Thoracoscopy is the diagnostic method of choice for pleural effusions
      in patients with malignant tumors. If a malignant pleural effusion is confirmed,
      a talc poudrage represents the most reliable treatment to palliate the dyspnea.
      The resection of a single solitary pulmonary metastasis can be indicated to
      confirm the histologic type of the nodule. Resections for centrally localized
      lesions causing hemoptysis or atelectasis represent rare occasions. Metastatic
      lesions of breast cancer involving the ribs or the sternum are resected in order
      to confirm the histologic diagnosis. According to the literature these
      procedures, with a 5-year survival rate of 50% and without perioperative
      mortality, can be beneficial.

PMID- 10063595
TI  - [Surgery of lung metastases in breast carcinoma].
AB  - The resection of lung metastases as a component of a multistep therapeutic
      concept is an established treatment approach. 5-year survival rates of 30% are
      attainable in combination with a low postoperative lethality. We performed 99
      operations on 89 patients with lung metastases between 1977 and 1997 in the
      Department of Thoracic Surgery on the Carl-Thiem-Klinikum Cottbus. No
      postoperative lethality was observed.

PMID- 10063596
TI  - [Treatment strategies in malignant pleural effusion of breast carcinoma].
AB  - Symptoms are dyspnea, pain and reduced common feeling. Aine of the study was, to
      compare our results of talc pleurodesis with the literature. In a prospective
      trial we performed talc pleurodesis via a chest tube in 41 patients. All patients
      had radiologically proven pleural effusions. No additional therapy was permitted
      30 days before or after entry into the study. Response was assessed monthly.
      Seven patients dies because of tumor progress. We examined 34 patients. Treatment
      was successful in 31 patients adverse effects we saw only a few times.
      Application of iodized talc for therapy of malignant pleural effusions is
      effective and cheep. We did not see major adverse effects or complications.

PMID- 10063597
TI  - [Surgical therapy of liver metastases in breast carcinoma].
AB  - The literature contains little information on the surgical treatment of
      metastases from carcinoma of the breast. Advanced stages of mammary cancer with
      generalised metastatic spread are considered to be the therapeutic domain of
      systemic chemotherapy. Patients with isolated liver metastases may, under certain
      circumstances, be considered candidates for partial resection of the liver.
      Another therapeutic option in this group of patients is intraarterial
      chemotherapy via a port catheter system implanted in the hepatic artery. A number
      of institutions employ a combination of both treatment modalities. Overall 5-year
      survival rates are low for both the regional and the systemic form of treatment.
      A carefully selected group of patients may be expected to benefit from partial
      resection of the liver, intraarterial chemotherapy or a combination of the two by
      having their survival time prolonged--provided that due consideration is given to
      all contraindications, and there are no extrahepatic manifestations. Wherever
      possible, resections should be carried out in curative intent. However,
      palliative resection may be justified in individual cases where alleviation of
      symptoms and an improvement in the patient's quality of life is to be expected.
      The present paper discusses the results achieved in 21 women who underwent liver
      resection at the surgical department of the University of Erlangen between 1980
      and 1997, and compares these results with those reported in the literature. The
      average age of the patients was 54 years, and 9 had a solitary metastasis. As was
      to be expected, the R classification had a decisive influence on survival. The 2
      year survival rate was 60% for R0 resections as compared with 16.7% for R1 or R2
      resections.

PMID- 10063598
TI  - [Surgical treatment of bone metastases in breast carcinoma].
AB  - The operative treatment of skeletal metastases takes only a small part of the
      total of traumatology and orthopaedic treatments. They should taken within the
      scope of an interdisciplinary treatment plan and mean a palliative step. The
      pathological fracture is, especially such of the spinal column and the long bones
      an absolute indication for stabilisation. The prophylactic stabilisation has
      priority by patients with osteolyses, because essential benefits. 48 operative
      steps in all has been taken between 1995 and 1997 in the "Zentrum fur Orthopadie,
      Unfall- und Wiederherstellungschirurgie" of the Klinikum Suhl.

PMID- 10063599
TI  - [Preoperative chemotherapy of breast carcinoma].
AB  - Preoperative chemotherapy represents the standard procedure in inflammatory
      breast cancer. However, only recently it could be demonstrated that preoperative
      chemotherapy is beneficial even for patients with operable primary breast cancer.
      The number of breast conserving surgeries could be increased significantly.
      Furthermore this in vivo chemosensitivity assay can provide important prognostic
      as well as predictivy informations. Preoperative chemotherapy is not associated
      with an increased risk for the patients as outcome is similar to patients with
      conventional adjuvant treatment. We investigated new regimens to improve this
      type of chemotherapy and reached a remission rate of 93% with a combination of
      adriamycin and docetaxel (ADoc). A randomized study (GEPARDO-study) comparing
      ADoc with ADoc + tamoxifen has recently been started in Germany by the German
      Adjuvant Breast Cancer Study Group (GABG).

PMID- 10063600
TI  - [Recommendations for adjuvant chemo- and hormone therapy of breast carcinoma].
AB  - Recommendations for adjuvant treatment of patients with breast cancer are given
      based on the International Consensus panel of adjuvant Therapy of Breast Cancer
      in St. Gallen in 1998. Possible therapeutical options (antihormonal therapy,
      chemotherapy with CMF or EC/AC) are discussed in dependence on the risc of
      recurrence. Problems of individual therapeutical strategies are discussed
      additionally.

PMID- 10063601
TI  - [Neoadjuvant chemotherapy of patients with breast carcinoma].
AB  - Adjuvant therapy has shown to be of significant benefit in patients with breast
      cancer. Among the possibilities to further improve the results, preoperative
      chemotherapy is a promising tool. So far, we have treated 178 patients and found
      that downstaging permits breast conservation in 60% of patients who would
      otherwise undergo mastectomy. The significance of this method for further
      improvement of survival has to await results of ongoing trials.

PMID- 10063602
TI  - [Hormone replacement therapy (HRT) in peri- and postmenopause. Is it also allowed
      after treatment of breast carcinoma?].
AB  - Hormone Replacement Therapy (HRT) is an approved strategy of health care. Its
      characteristic features and benefits for women in the perimenopausal and
      postmenopausal state are represented. HRT is justifiable and necessary for
      prophylaxis and therapy of estrogen deficiency. The risk of breast cancer is not
      or only little increased. HRT can even take place after the therapy of breast
      cancer, if the consequences of the ovarian hormone deficiency can be diminished
      only by this method. Then the advantages preponderate over the theoretically
      possible risks. The mortality of women ist rather reduced by HRT.

PMID- 10063603
TI  - [Primary chemotherapy of metastatic breast carcinoma with bendamustine
      hydrochloride, methotrexate and fluorouracil versus cyclophosphamide,
      methotrexate and fluorouracil].
AB  - The combination bendamustine/methotrexate/fluorouracil (BMF) was proven versus
      cyclophosphomide/methotrexate/fluorouracil (CMF) in a stratified randomized pilot
      study as primary chemotherapy in 61 patients with metastatic breast cancer.
      Bendamustine was given in a dose of 240 mg/m2 and cyclophosphamide in a dose of
      960 mg/m2 per therapy-cycle. The doses of methotrexate (40 mg/m2 i.v., day 1 and
      8) and fluorouracil (500 mg/m2 i.v., day 1 and 8) were identical in both groups.
      25 patients in the BMF- and 24 patients in the CMF-group were evaluable. The
      remission rates were 52% vs. 46%. The median duration of remission was 15.2
      months (ranging from 8.1 to 19.7 months) in the BMF-group and 6.2 months (ranging
      from 1.9 to 11.1 months) in the CMF-group. The aim of this study was to identify
      the main criterion for further randomized studies. The results of this pilot
      study indicate, that it is possible to prolong the median duration of remission
      without changing the antineoplastic activity by replacing cyclophosphamide with
      bendamustine.

PMID- 10063604
TI  - [Value of locoregional chemotherapy in liver metastases of breast carcinoma].
AB  - Between 1985 and 1997, we performed a locoregional chemotherapy in 59 patients
      suffering from non-resectable liver metastases of breast cancer. 36 of them only
      had liver metastases, in 23 patients liver metastases were combined with
      extrahepatic tumor spread. Furthermore, in 7 patients locoregional chemotherapy
      was used as a adjuvant regimen after metastasectomy. The average age of our
      patients was 52 (32-81) years. In most of our patients, a cytostatic scheme of
      mitoxantron, 5-fluorouracil and doxorubicin or a scheme of vincristin, mitomycin
      and mitoxantron was administered. The median survival of all patients was 11
      months, in the patients with no additional extrahepatic tumor spread it was 16,
      in the patients with extrahepatic metastases 3 months, respectively.

PMID- 10063605
TI  - [High dosage chemotherapy and peripheral blood stem cell transplantation in
      breast carcinoma].
AB  - Chemotherapeutic agents have been shown experimentally to have a dose-response
      relationship in drug-sensitive cancer. This suggests that high-dose chemotherapy
      (HDC) might improve the therapeutic outcome in breast cancer. The emergence of
      modern supportive measures like peripheral blood stem cell rescue has
      significantly decreased the toxicity and cost of HDC. HDC is being employed for
      patients with metastatic and high-risk breast cancer (> 10 involved axillary
      lymph nodes). Randomized phase III trials are urgently needed. At the moment
      patient with breast cancer should only be treated with HDC in context with a
      clinical trial.

PMID- 10063606
TI  - [Inpatient rehabilitation of breast carcinoma patients].
AB  - Aim of a holistic in-patient rehabilitation program for female breast cancer
      patients is to strengthen the air overall health and help them to overcome the
      sometimes severe therapeutic side effects. In addition it is important for the
      patient to learn how to compensate with any residual physical effects and last
      but not least psychological support for coping with the malignant disease.
      Furthermore, a major target is, aside from improving the general state of health,
      the patient's reintegration into working life, if the disease is in a potentially
      curable state with a good chance for survival. If vocational reintegration fails
      due to the advanced state of the cancer or therapy induced damage or handicaps,
      which unfortunately applies to most of the patients, at least reintegration into
      private and social life should be achieved. To realize these objectives effective
      methods of treatment have been developed which can best be performed in
      specialized rehabilitation centres which are closely affiliated to cancer
      centres.

PMID- 10063607
TI  - [Report by the German Society of Senology].

PMID- 10063608
TI  - Gangliosides asymmetrically alter the membrane order in cultured PC-12 cells.
AB  - Exogenous gangliosides readily associate with the cell membranes and produce
      marked effects on cell growth and differentiation. We have studied the effect of
      bovine brain gangliosides (BBG) on the membrane dynamics of intact cells. The
      structural and dynamic changes in the cell membrane were monitored by the
      fluorescence probes DPH, TMA-DPH and laurdan. Incorporation of BBG into the cell
      membrane decreased the fluorescence intensity, lifetime and the steady state
      anisotropy of TMA-DPH. Analysis of the time resolved anisotropy decay by wobbling
      in the cone model revealed that BBG decreased the order parameter, and increased
      the cone angle without altering the rotational relaxation rate. The fluorescence
      intensity and lifetime of DPH were unaffected by BBG incorporation, however, a
      modest increase was observed in the steady state anisotropy. BBG incorporation
      reduced the total fluorescence intensity of laurdan with pronounced quenching of
      the 440-nm band. The wavelength sensitivity of generalized polarization of
      laurdan manifested an ordered liquid crystalline environment of the probe in the
      cell membrane. BBG incorporation reduced the GP values and augmented the liquid
      crystalline behavior of the cell membrane. BBG incorporation also influenced the
      permeability of cell membranes to cations. An influx of Na+ and Ca2+ and an
      efflux of K+ was observed. The data demonstrate that incorporation of
      gangliosides into the cell membrane substantially enhances the disorder and
      hydration of the lipid bilayer region near the exoplasmic surface. The inner core
      region near the center of the bilayer becomes slightly more ordered and remains
      highly hydrophobic. Such changes in the structure and dynamics of the membrane
      could play an important role in modulation of transmembrane signaling events by
      the gangliosides.

PMID- 10063609
TI  - Peptide-bilayer interactions: simulations of dermaseptin B, an antimicrobial
      peptide.
AB  - Dermaseptins, a family of antimicrobial peptides, are believed to act by forming
      amphipathic alpha-helices which associate with the cell membrane, leading to its
      permeabilisation and disruption. A simple mean field method is described for
      simulation of the interactions of peptides with lipid bilayers which includes an
      approximate representation of the electrostatic effects of the head-group region
      of the bilayer. Starting from an atomistic model of a PC phospholipid bilayer we
      calculate an average electrostatic potential along the bilayer normal. By
      combining the interaction of the peptide with this electrostatic potential and
      with the hydrophobic core of the membrane we arrive at a more complete
      description of peptide-bilayer energetics than would be obtained using sidechain
      hydrophobicities alone. Using this interaction potential in MD simulations of the
      frog skin peptide dermaseptin B reveals that the lipid bilayer stabilises the
      alpha-helical conformation of the peptide. This is in agreement with FTIR data. A
      surface associated orientation thus appears to be the most stable arrangement of
      the peptide, at least at zero ionic strength and without taking account of
      possible peptide-peptide interactions.

PMID- 10063610
TI  - The contribution of personal resources to physical and mental health: looking
      into age and gender effects.
AB  - In this study, a model that specified the effects of socioeconomic and
      psychological resources on physical and mental health was investigated. It was
      hypothesized that (a) both kinds of resources would affect physical and mental
      health more strongly in older than in younger adults, and that (b) socioeconomic
      resources would exert stronger effects in men, whereas psychological resources
      would exert stronger effects in women. Data were collected in an Israeli national
      sample. Structural modeling analyses indicated that the model fit the data. A
      comparison of 4 groups of participants (2 age groups--18-39 and 40-84--and both
      genders) showed that, for men, the respective effects of socioeconomic and
      psychological resources on physical and mental health were strong in the older,
      but not in the younger, group. For women, socioeconomic resources had
      nonsignificant effects, whereas psychological resources had strong effects on
      mental health in both age groups; psychological resources also had a moderate
      effect on physical health in the older group. The results suggest that the
      contribution of personal resources to health is regulated by the joint impact of
      age and gender, presumably involving shifting roles and vulnerabilities of men
      and women across the life span.

PMID- 10063611
TI  - Parenting characteristics and adolescent psychological well-being: a longitudinal
      study in a Chinese context.
AB  - In this longitudinal study, the relationships between perceived parenting
      characteristics and adolescent psychological well-being were examined in a sample
      of Hong Kong Chinese adolescents (N = 378). The results indicated that global
      parenting styles and specific parenting behaviors are concurrently related to
      hopelessness, life satisfaction, self-esteem, purpose in life, and general
      psychiatric morbidity at Time 1 and Time 2. Longitudinal and prospective analyses
      (Time 1 predictors of Time 2 criterion variables) suggested that the relations
      between parenting characteristics and adolescent psychological well-being are
      bidirectional in nature. The results indicated that the strengths of association
      between perceived parenting characteristics and adolescent psychological well
      being are stronger in female than in male adolescents. Relative to maternal
      parenting characteristics, paternal parenting was found to exert a stronger
      influence on adolescent psychological well-being.

PMID- 10063612
TI  - Human memory, cerebral hemispheres, and the limbic system: a new approach.
AB  - An integrative approach to human memory is presented in the context of brain
      asymmetry. The results of psychophysiological investigations suggest that right
      hemisphere functioning is closely associated with the limbic system; that
      association leads to the formation of a polysemantic context. Polysemantic
      context is determined by multiple interconnections among its elements; each
      element bears the stamp of the whole context. That context sustains episodic,
      personal, and emotionally laden memories. Left-hemisphere functioning leads to
      the formation of a monosemantic context, which is responsible for the maintenance
      of semantic memories. That distinction--in terms of general organization of
      material by hemispheres--explains such phenomena as memory disturbances among the
      very old, the influence of emotions on memory, and confabulations.

PMID- 10063613
TI  - Frontal lobe deficits in domestic violence offenders.
AB  - Functional frontal lobe deficits were examined in 38 men who committed domestic
      violence and 38 control participants. Dependent measures that examine frontal
      lobe deficits, including the Wisconsin Card Sorting Test (D. A. Grant & E. A.
      Berg, 1948), the Stroop Color-Word Test (J. R. Stroop, 1935), and Trails B (R. M.
      Reitan & L. A. Davidson, 1974), were used. The prediction that men who commit
      domestic violence would perform more poorly on neuropsychological measures
      related to frontal lobe deficits was only partially supported. A discriminate
      analysis was significant (p < .05), explaining approximately 7% of the variance;
      Trails B was the only contributor to that equation. The men who committed battery
      took significantly longer to complete Trails B than the control participants,
      suggesting that the men who committed battery may not have been as good as the
      control participants at inhibiting the competing response and therefore took
      longer to complete the task. The groups did not significantly differ on the other
      neuropsychological measures.

PMID- 10063614
TI  - Partial characterization and cloning of leuconocin J, a bacteriocin produced by
      Leuconostoc sp. J2 isolated from the Korean fermented vegetable Kimchi.
AB  - Leuconostoc sp. J2, isolated from naturally fermented Kimchi, produced a
      bacteriocin which was named leuconocin J. This bacteriocin exhibited an
      inhibitory activity against several lactic acid bacteria and some food-borne
      pathogens. The antimicrobial substance was secreted into the medium during the
      late log phase. It appears to be proteinaceous since its activity was completely
      inactivated by a range of proteolytic enzymes, and it was also relatively heat
      stable. The bacteriocin was partially purified by ammonium sulphate
      precipitation, following dialysis. The apparent molecular mass of partially
      purified bacteriocin, as indicated by activity detection after Tricine-SDS-PAGE,
      was 2.5-3.5 kDa. Leuconostoc sp. J2 plasmid DNA digested by EcoRI was cloned into
      pUC118 and transformed into Escherichia coli DH5 alpha. Phenotypic expression of
      the bacteriocin production was detected in transformants harboring pULBJ5.5.
      Finally, Southern blotting with the 2.3 kb insert as a probe against plasmid
      digests of Leuconostoc sp. J2 revealed that the cloned foreign DNA originated
      from Leuconostoc sp. J2.

PMID- 10063615
TI  - Production of lysozyme-enriched biomass from cheese industry by-products.
AB  - Cheese whey and cottage cheese whey are by-products of the milk and cheese
      industry, resulting from the production of cheese and cottage cheese (ricotta)
      from milk. They are still rich in organic substances and cannot be discarded into
      the environment without proper treatment. Whey and cottage cheese whey were used
      as culture media for some strains of the yeast Kluyveromyces lactis, transformed
      with the human lysozyme gene. It was found that the yeast strains grew well in
      both media and produced a considerable amount of recombinant protein. Production
      kinetics showed that the human lysozyme was produced in a greater amount within
      36 h of fermentation (125 micrograms ml-1 vs 25 micrograms ml-1 in the control)
      than in the synthetic commercial media used for strain preparation and
      characterization. The recombinant protein produced was actually shown to be the
      human lysozyme, using renaturing SDS-PAGE and Western blot techniques. While
      producing recombinant protein, the Kluyveromyces strain cleared the cottage
      cheese whey of most organic substances and produced a considerable amount (almost
      3%) of lysozyme-enriched useful biomass.

PMID- 10063616
TI  - DNA probes specific for Aeromonas hydrophila (HG1).
AB  - Aeromonas hydrophila (HG1)-specific RAPD-PCR fragments were investigated for
      their potential as DNA probes. From 20 RAPD-PCR fragment bands, it was found that
      two were specific to all isolates of Aeromonas hydrophila (HG1) tested. Cloning
      and nucleotide sequence determination of one of these bands showed that co
      migration of similar sized amplicons had occurred and that this band (designated
      '7e') contained at least four fragments of different sequences. Three of these
      individual amplicons had a sequence specific to Aer. hydrophila (HG1) isolates.
      The sequence of one of these amplicons ('7e5') was used to design primers for a
      specific polymerase chain reaction (PCR). The specificity of the PCR was achieved
      using a modified hot-start procedure. The identity of the PCR amplicons was
      confirmed by high stringency hybridization with a digoxygenin-labelled 7e5 probe.

PMID- 10063617
TI  - Use of a modified Robbins device to directly compare the adhesion of
      Staphylococcus epidermidis RP62A to surfaces.
AB  - Staphylococcus epidermidis is a frequent cause of infection associated with the
      use of biomedical devices. Flow cell studies of the interaction between bacteria
      and surfaces do not generally allow direct comparison of different materials
      using the same bacterial suspension. The use of a modified Robbins Device (MRD)
      to compare the adhesion to different surfaces of Staph. epidermidis RP62A grown
      in continuous culture was investigated. Adhesion to glass was compared with
      siliconized glass, plasma-conditioned glass, titanium, stainless steel and
      Teflon. Attachment to siliconized glass was also compared with glass under
      differing ionic strength, and divalent cation concentrations. Both the
      differences in numbers adhering and changes in adhesion (slope) through the MRD
      were compared. There was a trend towards higher numbers adhering to the discs at
      the in-flow end of the MRD than at the outflow end, probably reflecting depletion
      of adherent bacteria in the interacting stream. Adhesion of Staph. epidermidis
      RP62A to siliconized glass and Teflon was reduced when compared to glass with
      increasing flow rates. Adhesion to stainless steel was not affected by flow rate
      and titanium gave a different slope of adhesion through the MRD when compared
      with glass, suggesting an interaction with different sub-populations within the
      interacting stream. Differences between siliconized glass and glass at flow rates
      of 300 ml h-1 were abolished by the addition of calcium or EDTA and reduced by
      the addition of magnesium. Increasing ionic strength reduced the statistical
      significance of the differences between glass and siliconized glass. Pre
      conditioning of glass with pooled human plasma reduced adhesion compared with
      untreated glass and again gave a different slope to glass. The MRD linked to a
      chemostat can be used to compare directly bacterial adhesion to potential
      biomaterials. Variable depletion of the interacting stream should be taken into
      account in the interpretation of results. Divalent cation concentration,
      substrate properties and flow rate were important determinants of the comparative
      adhesion of Staph. epidermidis RP62A to surfaces.

PMID- 10063618
TI  - Tolerance of acid-adapted and non-adapted Escherichia coli O157:H7 cells to
      reduced pH as affected by type of acidulant.
AB  - A study was carried out to determine if three strains of Escherichia coli O157:H7
      grown (18 h) in Tryptic Soy Broth (TSB) and TSB supplemented with 1.25% glucose
      (TSBG), i.e. unadapted and acid-adapted cells, respectively, exhibited changes in
      tolerance to reduced pH when plated on Tryptic Soy Agar (TSA) acidified (pH 3.9,
      4.2, 4.5, 4.8, 5.1 and 5.4) with acetic, citric or malic acids. All test strains
      grew well on TSA acidified with acetic acid at pH > or = 5.4 or malic acid at pH
      > or = 4.5; two strains grew on TSA acidified with citric acid at pH > or = 4.5,
      while the third strain grew at pH > or = 4.8. Acid-adapted and control
      (unadapted) cells differed little in their ability to form visible colonies on
      TSA containing the same acid at the same pH. However, on plates not showing
      visible colonies, acid-adapted cells retained higher viability than unadapted
      cells when plated on acidified TSA. Growth of acid-adapted and control cells of
      E. coli O157:H7 inoculated into TSB containing acetic acid (pH 5.4 and 5.7) and
      citric or malic acids (pH 4.2 and 4.5) was also studied. There was essentially no
      difference in growth characteristics of the two types of cells in TSB acidified
      at the same pH with a given acid. Tolerance of acid-adapted and control cells on
      subsequent exposure to low pH is influenced by the type of acidulant. The order
      of sensitivity at a given pH is acetic > citric > malic acid. When performing
      acid challenge studies to determine survival and growth characteristics of E.
      coli O157:H7 in foods, consideration should be given to the type of acid to which
      cells have been exposed previously, the procedure used to achieve acidic
      environments and possible differences in response among strains. The use of
      strains less affected by pH than type of acidulant or vice versa could result in
      an underestimation of the potential for survival and growth of E. coli O157:H7 in
      acid foods.

PMID- 10063620
TI  - Study of the micro-organisms associated with the fermented bread (khamir)
      produced from sorghum in Gizan region, Saudi Arabia.
AB  - Traditional bread (khamir) was made from sorghum flour of two local varieties,
      Bayadh and Hamra. The bread was prepared by mixing the sorghum flour with water
      and spices (onion, garlic, lemon juice and fenugreek) in a 1:0.8 (w/w) ratio and
      fermented for 24 h at 30 degrees C. Two other fermentations were carried out
      using an inoculum from the previous fermentation. The micro-organisms were
      isolated from different plates and identified using different characterization
      systems. Both total bacterial populations and lactic acid bacteria increased with
      fermentation time and reached the highest number at 16 h (first fermentation) and
      at 8 h (second and third fermentation). The content of lactic acid was increased
      with time to reach 1.2%, but the increase was higher for the second and third
      fermentations (1.6% each). The pH dropped with time from 6.77 to 4.35 in the
      first fermentation and from 6.65 to 4.18, and 6.57-3.93, in the second and third
      fermentations, respectively. The microorganisms, which were isolated and
      characterized during the 24 h fermentation, included: bacteria (Pediococcus
      pentosaceus, Lactobacillus brevis, Lact. lactis subsp. lactis, Lact. cellobiosus,
      Klebsiella oxytoca, Kl. pneumoniae, Enterobacter aerogenes, Ent. sakazakii,
      Serratia marcescens and Ser. odourifera), moulds (Penicillium sp., Rhizopus sp.,
      Aspergillus niger, Alternaria sp., Fusarium sp. and Mucor sp.) and yeasts
      (Candida parapsilosis, C. orvegnsis and Rhodotorula glutinis).

PMID- 10063621
TI  - A method for the preparation of Tetrahymena thermophila phospholipase A1 suitable
      for large-scale production.
AB  - A rapid and economical method for the purification of phospholipase A1 (PLA1)
      from the extracellular medium of the ciliate Tetrahymena thermophila is
      presented. Essentially, the procedure, here designated as purification by
      selective interaction (PSI), entails the incubation of media containing PLA1 with
      liposomes made of soy bean phospholipids. The PLA1-lipid complexes are
      precipitated by the addition of CaCl2 and collected by centrifugation. Elution of
      the PLA1 is effected by treating the complexes with 40% dimethylformamide, a
      reversible inhibitor of this enzyme, which is easily removed by dialysis. In
      combination with DEAE cellulose ion exchange chromatography, PSI yielded
      homogeneous PLA1 preparations with a 14% recovery and a 416-fold increase in
      specific activity. This procedure, which can be completed within 1 day, may prove
      useful for the isolation of phospholipases from other sources. This practical
      method for the purification of a microbial PLA1 opens the way to large-scale
      production of these types of enzyme, which are not as yet commercially available.

PMID- 10063622
TI  - Rapid enumeration of Escherichia coli in oysters by a quantitative PCR-ELISA.
AB  - Direct enumeration of Escherichia coli from oysters was achieved using a
      polymerase chain reaction (PCR) amplification of the lamB gene coupled with an
      enzyme-linked immunosorbent assay (ELISA). Amplified PCR products generated using
      a digoxigenin-labelled primer were heat denatured before being quantified by an
      ELISA. A biotinylated probe immobilized onto streptavidin-coated microplates was
      used to capture the digoxigenin-labelled fragments that were detected with a
      peroxidase antidigoxigenin conjugate. Subsequent enzymic conversion of substrate
      gave distinct absorbance differences when assaying oyster samples containing E.
      coli in the range 10-10(5) cfu g-1.

PMID- 10063623
TI  - Role of the 25 kDa major outer membrane protein of Legionella pneumophila in
      attachment to U-937 cells and its potential as a virulence factor for chick
      embryos.
AB  - The gene encoding the 25 kDa major outer membrane protein (MOMP) of Legionella
      pneumophila was transformed into Escherichia coli JM 83 and the resultant E. coli
      LP 116 clone expressed the Legionella-MOMP. Compared with the parent E. coli
      strain, the clone showed a fivefold increase in opsonin-independent binding to U
      937 cells. Furthermore, this gene was incorporated by electroporation into a low
      virulence derivative of Leg. pneumophila which showed reduced expression of the
      MOMP but enhanced expression of a 31 kDa protein in the OMP profile. After
      electroporation, the attenuated strain showed an increased expression of the MOMP
      while the 31 kDa protein was eliminated and virulence for the chick embryo was re
      established. The use of a monoclonal antibody specific for the MOMP abolished
      virulence and adherence. These studies suggest that the 25 kDa MOMP of Leg.
      pneumophila serves as an adhesive molecule for host cells and that this protein
      plays a major role in the virulence of the organism for the chick embryo.

PMID- 10063624
TI  - The effect of sucrose or starch-based diet on short-chain fatty acids and faecal
      microflora in rats.
AB  - An investigation was carried out to determine whether variations of dietary
      carbohydrates could modify the colonic flora in rats. Sprague-Dawley rats were
      fed with two equicaloric diets based on the AIN-76 diet (American Institute of
      Nutrition 1977) but differing from that diet in content of carbohydrates, i.e.
      high sucrose (64%) of high corn starch (64%). Feeding was continued for 9 months
      ad libitum and no variation in weight gain was recorded among the different
      diets. A prevalence of aerobes, and a significant reduction in the ratio
      anaerobes/aerobes in the faeces of rats on the high starch diet compared with the
      high sucrose diet, was observed. The anaerobe genera identified included
      Actinomyces, Bacteroides, Bifidobacterium, Clostridium, Eubacterium,
      Lactobacillus and Propionibacterium. Bacteroides was the most prevalent genus in
      both dietary groups (51.2 and 29.5% in the faeces of rats fed the sucrose and
      starch diets, respectively). In contrast, clostridia were prevalent in the starch
      fed group (23.8%) and less so in the sucrose diet (11.5%), as propionibacteria
      were prevalent in faeces of rats fed the starch diet (15.5%), and low in the
      sucrose diet (3.9%). The remaining genera were scarce in faeces from rats on
      either diet. Total short-chain fatty acids (SCFA) were significantly higher in
      the faeces of animals fed the starch diet compared with those fed the sucrose
      diet. The relative concentrations of acetic, propionic and butyric acids were not
      significantly different between the two dietary groups. In conclusion, high
      starch diet can markedly modify the composition of faecal flora and alter
      considerably the faecal concentration of SCFAs, compound which might have a
      health-promoting effect.

PMID- 10063625
TI  - Inhibition of Listeria monocytogenes in cottage cheese manufactured with a
      lacticin 3147-producing starter culture.
AB  - The efficacy of using a lacticin 3147-producing starter as a protective culture
      to improve the safety of cottage cheese was investigated. This involved the
      manufacture of cottage cheese using Lactococcus lactis DPC4268 (control) and L.
      lactis DPC4275, a bacteriocin-producing transconjugant strain derived from
      DPC4268. A number of Listeria monocytogenes strains, including a number of
      industrial isolates, were assayed for their sensitivity to lacticin 3147. These
      strains varied considerably with respect to their sensitivity to the bacteriocin.
      One of the more tolerant strains, Scott A, was used in the cottage cheese study;
      the cheese was subsequently inoculated with approximately 10(4) L. monocytogenes
      Scott A g-1. The bacteriocin concentration in the curd was measured at 2560 AU ml
      1, and bacteriocin activity could be detected throughout the 1 week storage
      period. In cottage cheese samples held at 4 degrees C, there was at least a 99.9%
      reduction in the numbers of L. monocytogenes Scott A in the bacteriocin
      containing cheese within 5 d, whereas in the control cheeses, numbers remained
      essentially unchanged. At higher storage temperatures, the kill rate was more
      rapid. These results demonstrate the effectiveness of lacticin 3147 as an
      inhibitor of L. monocytogenes in a food system where post-manufacture
      contamination by this organism could be problematic.

PMID- 10063626
TI  - The certification of a reference material for the evaluation of methods for the
      enumeration of Bacillus cereus.
AB  - A reference material containing Bacillus cereus was certified by the Community
      Bureau of Reference (BCR) for its number of colony-forming particles (cfp) in 0.1
      ml reconstituted capsule solution. To this end, a batch of approximately 15,000
      capsules was produced and tested for its homogeneity and stability. The variation
      in the number of cfp between capsules (homogeneity) was not found to be
      significantly different from a Poisson distribution. Stability was tested for
      extended periods at storage temperature (-20 degrees C) and at various higher
      temperatures up to 37 degrees C for 4 weeks to simulate transport conditions.
      Only at 37 degrees C did a small but significant decrease in the number of cfp
      occur. At -20 degrees C, no decrease in the number of cfp was observed over a
      period of about 4 years. For certification, 12 laboratories determined the number
      of cfp on two agars: Mannitol Egg-Yolk Polymyxin agar (MEYP, incubated at 30
      degrees C) and Polymyxin pyruvate Egg-yolk Bromothymol blue Agar (PEMBA,
      incubated at 37 degrees C). The certified geometric mean value on MEYP after 24 h
      of incubation was 53.4 cfp 0.1 ml-1 of the reconstituted capsule solution (95%
      confidence interval 51.7-55.2) and on PEMBA, 55.0 (95% confidence interval 52.8
      57.4). Based on these certified values, user tables were constructed specifying
      the 95% confidence limits when testing a smaller number of capsules, as would be
      done in individual laboratories. Based on the information on homogeneity,
      stability and the certification study, the BCR decided to certify the material as
      CRM 528.

PMID- 10063627
TI  - Electrotransformation of industrial strains of Streptococcus thermophilus.
AB  - A standard electroporation procedure was utilized to introduce a range of Gram
      positive plasmid vectors into nine industrial strains of Streptococcus
      thermophilus. All the strains were transformable with at least two of the
      plasmids assessed, but electrotransformation frequencies depended on both the
      strain and the nature of transforming DNA. In general, small rolling circle (RC)
      plasmids could be electroporated at high frequency into a wide range of strains
      with efficiencies of 10(2)-10(5) transformants microgram-1 of transforming DNA.
      The presence of these plasmids did not influence doubling times during growth in
      broth, and they were generally extremely stable in slow milk acidifying strains,
      with 85-100% of transformants retaining the selective markers over 105
      generations. Vectors were less stable in fast-growing cultures. Of the three
      theta-type plasmids assessed, only one, pIL253, could be electroporated at low
      frequency into some slow growing strains. The presence of this plasmid caused a
      40% increase in doubling time and it was lost from cells at a rate of 3% per
      generation. Attempts to alter the proteolytic status of slow acidifying strains
      of Strep. thermophilus by the introduction of heterologous proteinase genes are
      also described.

PMID- 10063628
TI  - Characterization of Saccharomyces cerevisiae strains from spontaneously fermented
      maize dough by profiles of assimilation, chromosome polymorphism, PCR and MAL
      genotyping.
AB  - Several isolates of Saccharomyces cerevisiae from indigenous spontaneously
      fermented maize dough have been characterized with the purpose of selecting
      appropriate starter cultures and methods for their subspecies typing. The
      techniques applied included assimilation of carbon compounds by the API ID 32 C
      kit, determination of chromosome profiles by PFGE, PCR and MAL genotyping. For
      the 48 isolates investigated, use of the API ID 32 C kit resulted in eight
      different assimilation profiles. The most common assimilation profile was the
      ability of 50% of the isolates to assimilate galactose, saccharose, DL-lactate,
      raffinose, maltose and glucose. Both chromosome and PCR profiles could be used
      for subspecies typing of the isolates and on this basis, the isolates were
      grouped into clusters. The discriminative power of the two techniques was equal;
      a few isolates not separated by their chromosome profiles could be separated by
      their PCR profiles and vice versa. Four different MAL genotypes were observed
      with MAL11 and MAL31 predominating. MAL11 was seen for all isolates whereas no
      evidence of MAL21 and MAL41 was observed. Based on the results obtained, a high
      number of Saccharomyces cerevisiae isolates were found to be involved throughout
      the spontaneous fermentation of maize dough. All methods included appeared to be
      suitable for subspecies typing. However, the discriminative power was highest for
      the PFGE and PCR techniques.

PMID- 10063629
TI  - Characterization of rpoS alleles in Escherichia coli O157:H7 and in other E. coli
      serotypes.
AB  - The rpoS nucleotide and predicted amino acid sequences from three Escherichia
      coli O157:H7 isolates were compared with those from three other E. coli isolates,
      including the likely O157:H7 progenitor, E. coli O55:H7. These clinical and
      environmental isolates all had identical sigma S amino acid sequences, while
      laboratory strains K12 and DH1 had three and one amino acid alterations,
      respectively, in comparison with the majority sequence. To extend the analysis of
      sigma S sequence conservation to include other Gram-negative bacteria, the E.
      coli sigma S sequences were compared with those from diverse Gram-negative
      organisms; sigma S sequence identities ranged from 50.2 to 99.7% among the
      available sequences. The results further confirm the existence of rpoS alleles
      among different E. coli strains, although all strains were classified as acid
      resistant with survival rates > 10% after 2 h exposure to pH 2.5. It was also
      found that all E. coli O157:H7 isolates tested had a unique nucleotide at
      position 543, thus differentiating these strains from other E. coli serotypes.

PMID- 10063630
TI  - Inhibition of Bacillus licheniformis spore growth in milk by nisin, monolaurin,
      and pH combinations.
AB  - The effects of nisin and monolaurin, alone and in combination, were investigated
      on Bacillus licheniformis spores in milk at 37 degrees C. In the absence of
      inhibitors, germinated spores developed into growing vegetative cells and started
      sporulation at the end of the exponential phase. In the presence of nisin (25 IU
      ml-1), spore outgrowth was inhibited (4 log10 reduction at 10 h). Regrowth
      appeared between 10 and 24 h and reached a high population level (1.25 x 10(8)
      cfu ml-1) after 7 d. Monolaurin (250 micrograms ml-1) had a bacteriostatic effect
      during the first 10 h but thereafter, regrowth occurred slowly with a population
      level after 7 d (4 x 10(5) cfu ml-1) lower than that of nisin. Different combined
      effects of nisin (between 0 and 42 IU ml-1), monolaurin (ranging from 0 to 300
      micrograms ml-1), pH values (between 5.0 and 7.0) and spore loads (10(3), 10(4),
      10(5) spores ml-1) were investigated using a Doehlert matrix in order to study
      the main effects of these factors and the different interactions. Results were
      analysed using the Response Surface Methodology (RSM) and indicated that nisin
      and monolaurin had no action on spores before germination; only pH values had a
      significant effect (P < or = 0.001), i.e. spore count decreased as the pH value
      increased in relation to germination. Sublethal concentrations of nisin (30 IU ml
      1) and monolaurin (100 micrograms ml-1) in combination acted synergistically on
      outgrown spores and vegetative cells, showing total inhibition at pH 6.0, without
      regrowth, within 7 d at 37 degrees C.

PMID- 10063631
TI  - Properties of an L-glutamate-induced acid tolerance response which involves the
      functioning of extracellular induction components.
AB  - Escherichia coli became more acid tolerant following incubation for 60 min in a
      medium containing L-glutamate at pH 7.0, 7.5 or 8.5. Several agents, including
      cAMP, NaCl, sucrose, SDS and DOC, prevented tolerance appearing if present with L
      glutamate. Lesions in cysB, hns, fur, himA and relA, which frequently affect pH
      responses, failed to prevent L-glutamate-induced acid tolerance but a lesion in L
      glutamate decarboxylase abolished the response. Induction of acid tolerance by L
      glutamate was associated with the accumulation in the growth medium of a protein
      (or proteins) which was able to convert pH 7.0-grown cultures to acid tolerance,
      and the original L-glutamate-induced tolerance response was dependent on this
      component(s). Acid tolerance was also induced by L-aspartate at pH 7.0 and
      induction of such tolerance was dependent on an extracellular protein (or
      proteins). The L-glutamate and L-aspartate acid tolerance induction processes are
      further examples of a number of stress tolerance responses which differ from most
      inductions in that extracellular components, including extracellular sensors, are
      required.

PMID- 10063632
TI  - Protective effect of bifidus milk on the experimental infection with Salmonella
      enteritidis subsp. typhimurium in conventional and gnotobiotic mice.
AB  - The ability of Bifidobacterium bifidum from a commercial bifidus milk to
      antagonize Salmonella enteritidis subsp. typhimurium in vivo, and to reduce the
      pathological consequences for the host, was determined using conventional and
      gnotobiotic mice. Conventional animals received daily, by gavage, 0.1 ml bifidus
      milk containing about 10(9) cfu B. bifidum and germ-free animals received a
      single 0.1 ml dose. The conventional and gnotobiotic groups were challenged
      orally with 10(2) cfu of the pathogenic bacteria 5 and/or 10 d after the
      beginning of treatment. Control groups were treated with milk. Bifidus milk
      protected both animal models against the challenge with the pathogenic bacteria,
      as demonstrated by survival and histopathological data. However, to obtain the
      protective effect in gnotobiotic animals, the treatment had to be initiated 10 d
      before the challenge. In experimental and control gnotobiotic mice, Salm.
      enteritidis subsp. typhimurium became similarly established at levels ranging
      from 10(8) to 10(9) viable cells g-1 of faeces and remained at these high levels
      until the animals died or were sacrificed. It was concluded that the protection
      against Salm. enteritidis subsp. typhimurium observed in conventional and
      gnotobiotic mice treated with bifidus milk was not due to the reduction of the
      intestinal populations of the pathogenic bacteria.

PMID- 10063633
TI  - Clonality of Vibrio anguillarum strains isolated from fish from the Scandinavian
      countries, Sweden, Finland and Denmark.
AB  - In order to investigate whether outbreaks of vibriosis in the Baltic region were
      caused by the spread of certain pathogenic clones, 291 Vibrio anguillarum
      isolates from Finland (n = 156), Sweden (n = 88) and Denmark (n = 47) were
      studied with respect to serogroup, ribotype, plasmid content, and biochemical
      phenotypes as expressed with the PhenePlate (PhP) typing system. For comparison,
      54 V. anguillarum serogroup O1 from other countries worldwide were included. Most
      isolates from Finland, Sweden and Denmark belonged to serogroup O1 (255),
      followed by O2 (30). Four Finnish isolates cross-reacted strongly with antisera
      against two new serogroups VaNT2 and VaNT4, whereas two strains were non
      typeable. The serogroup O1 isolates displayed ten different ribotype patterns,
      whereas the other strains were considerably more diverse with respect to
      ribotypes. Most of the O1 isolates carried the 67 kb virulence plasmid and a
      group of Finnish isolates, in addition, carried an 86 kb plasmid. Additional
      plasmids with molecular weights of 63, 76, 135 or 260-290 kb were found in single
      O1 isolates. With few exceptions, strains of serogroup O2 either had no plasmids
      or carried one or two small plasmids. PhenePlate typing revealed considerable
      diversity within the species, serogroup O1 being the most homogeneous. A few PhP
      types were dominant, whereas other types were observed only in one to four
      isolates. The prevalence of the different types changed significantly from one
      year to another but in Finland, one clonal lineage became increasingly important
      from 1992 (20% of isolates) to 1996 (80%). Remaining clones were mostly
      restricted to specific geographic areas. By cluster analysis, it was demonstrated
      that most of the isolates from Finland, Sweden and Denmark belonged to two
      clusters, and most of the strains from Southern Europe fell into two other,
      distinct clusters. Most isolates from the UK, North America, Chile and Tasmania
      grouped together in a distinct cluster. For the typing of V. anguillarum, O
      serotyping should be the primary method. For isolates belonging to serogroups
      other than O1, plasmid profiling in combination with ribotyping gives a very good
      discrimination between strains, whereas for serogroup O1, another method is
      required. It is concluded that PhP typing is a tool that provides a good
      discrimination between O1 isolates.

PMID- 10063635
TI  - Note: evaluation of selective media for the enumeration of Bifidobacterium sp. in
      milk.
AB  - Pure cultures of three species of bifidobacteria (Bifidobacterium longum, Bif.
      adolescentis and Bif. bifidum), Lactobacillus acidophilus and a mixed culture of
      Lact. delbrueckii subsp. bulgaricus and Streptococcus salivarius subsp.
      thermophilus were each enumerated on two differential media and six selective
      media for the enumeration of bifidobacteria. The appearance of the colonies on
      the differential media was as expected but when mixed cultures were present, it
      proved extremely difficult to distinguish one species from another. Of the
      selective media, AMC, RMS, NPNL and BL-OG performed well in that they gave good
      recoveries of bifidobacteria and were inhibitory to the growth of Lact.
      delbrueckii subsp. bulgaricus, Strep. salivarius subsp. thermophilus and Lact.
      acidophilus. However, of these four media, AMC was most convenient as it is based
      on a commercially available medium, whereas the others must be made up from
      individual constituents. The AMC agar is thus a good choice for the routine
      enumeration of bifidobacteria from mixed cultures.

PMID- 10063636
TI  - The fate of environmental coliforms in a model water distribution system.
AB  - A series of experiments to determine the survival characteristics of
      environmental and faecal coliforms in a 1.3 km long experimental pipe
      distribution system is described. In the first experiments, tertiary treated
      effluent (10(3)-10(4) coliforms ml-1) was inoculated directly into the
      distribution system. Coliform organisms were not detected in any samples taken
      downstream of the inoculation point. By comparison, laboratory jar tests showed
      low level survival for coliforms at the same chloramine residuals (0.3 mg l-1)
      for up to 48 h. In the second series of experiments, a by-pass pipe in the
      experimental distribution system was isolated, drained, and filled with tertiary
      treated effluent (10(3)-10(4) coliforms ml-1) to simulate the conditions in a
      dead-end. Coliform numbers were monitored and found to decrease rapidly, but they
      were still detectable at low levels after 7 weeks. The water in the by-pass
      section was then released into the main pipe-rig and sampled downstream. No
      coliforms were detected in water samples or in samples swabbed from the pipe
      walls. Finally, the flow in the main pipe-rig and in the by-pass was increased to
      dislodge any deposits and biofilm into the water. The absence of coliforms in any
      water samples taken during or after the flow increases is contrary to the widely
      accepted understanding that coliforms survive and grow in biofilms on pipe walls.

PMID- 10063637
TI  - A new growth and in vitro sporulation medium for Clostridium perfringens.
AB  - Growth and in vitro sporulation capabilities of three related Clostridium
      perfringens strains (NCTC 8798, 8-6 and R3) were followed in a new sporulation
      medium (NSM), with notable changes from a maintenance medium originally designed
      for strictly anaerobic bacteria. Compared with thioglycollate (FTG) medium, the
      new sporulation medium promoted growth of Cl. perfringens with a shorter lag
      phase and a 20% higher biomass production. The age of inoculum did not change Cl.
      perfringens growth kinetics. When compared with reference conditions, in vitro
      spore production kinetics were different in the new sporulation medium, but both
      conditions led routinely to 100% sporulation and spore counts of approximately
      10(8) ml-1. The ease of preparation of the NSM, and the use of the same culture
      medium for good growth, high sporulation yields and spore production, represent
      an attractive alternative to the complex media routinely used for in vitro
      studies of Cl. perfringens physiology.

PMID- 10063638
TI  - Phototoxicity of rose bengal in mycological media--implications for laboratory
      practice.
AB  - The effects of Rose Bengal (RB) on plate counts of the bacteria Escherichia coli
      and Pseudomonas aeruginosa, and the yeast Saccharomyces cerevisiae, were studied
      under natural sunlight and artificial fluorescent lighting. While RB was not
      inherently toxic in darkness at concentrations found in mycological media, the
      illumination of media containing RB caused a decrease in colony counts in all
      cases, and especially for surface spread plates. A negative synergy was observed
      between chloramphenicol, RB and illumination using a spring water sample
      containing substantial numbers of Gram-negative bacteria. Exposure of media
      containing RB to moderate amounts of light during standard laboratory procedures
      may inhibit microbial growth, with positive benefits in relation to the
      suppression of contaminant bacteria, or negative implications where fungi are
      inhibited.

PMID- 10063639
TI  - Psychrotrophic clostridia mediated gas and botulinal toxin production in vacuum
      packed chilled meat.
AB  - A cocktail of washed spores from six psychrotrophic Clostridium strains isolated
      from blown vacuum-packed meats was inoculated onto lamb chumps. A second washed
      spore cocktail of four toxigenic reference Cl. botulinum strains, types A, B (two
      strains) and E, and a Cl. butyricum type E strain, was similarly inoculated onto
      lamb chumps. All inoculated lamb chumps were individually vacuum-packed and
      placed into storage at various temperatures typical of good to grossly abusive
      chilled storage (-1 degree C to 15 degrees C). All packs were observed for gas
      production (pack-'blowing') over a 12 week storage period. On gas production, or
      after 12 weeks of storage, packs were examined by mouse bioassay for botulinum
      toxin production. The packs inoculated with the meat isolate cocktail showed
      evidence of gas production earlier than packs inoculated with reference strains.
      No botulinum toxin was recovered from the meat isolate inoculated packs, while
      botulinal toxin was detected in reference strain inoculated packs down to a
      nominal storage temperature of 2 degrees C.

PMID- 10063640
TI  - Evaluation of a multiplex PCR assay for simultaneous identification of Salmonella
      sp., Salmonella enteritidis and Salmonella typhimurium from environmental swabs
      of poultry houses.
AB  - A Multiplex PCR-based assay (m-PCR) with three sets of primers was developed for
      the detection of all serotypes of Salmonella enterica and the identification of
      Salmonella Enteritidis and Salmonella Typhimurium. This method was evaluated
      against a bacteriological method for the analysis of environmental swabs of
      poultry houses. Samples were preenriched in phosphate-buffered peptone water for
      24 h and subjected to three different protocols prior to PCR: (i) an
      immunomagnetic separation using Dynabeads anti-Salmonella (Dynal); (ii) a DNA
      extraction procedure using the Instagene matrix; (iii) an additional step of
      culture on an MSRV medium. With protocols 1 and 2, eight positive results were
      found by PCR and 20 with the bacteriological method. Protocol 3 combining MSRV
      and PCR gave similar results to those obtained from bacteriological methods and
      allowed Salmonella detection within 2 days.

PMID- 10063641
TI  - Inhibitory effect of creosote and its main components on production of verotoxin
      of enterohaemorrhagic Escherichia coli O157:H7.
AB  - The inhibitory effects of creosote and its main components, alpha-methoxyphenol
      and o-ethylphenol, on production of verotoxin by enterohaemorrhagic Escherichia
      coli O157 (VTEC E. coli) were investigated. The production of verotoxin by VTEC
      E. coli was inhibited by the administration of 0.001-0.1% of creosote or o
      ethylphenol (final concentration). On the other hand, weak inhibition of
      production of verotoxin was observed with 0.1% alpha-methoxyphenol
      administration. As the inhibitory effects were obtained below Minimal Inhibitory
      Concentration (MIC) values, these test compounds exerted their effects at the
      active site of VTEC E. coli cells prior to their production of verotoxin. These
      findings suggest that pre-administration of creosote and its main components
      might prevent human intestinal food poisoning by VTEC E. coli and contribute to
      maintenance of public health.

PMID- 10063642
TI  - Biofilm formation by Helicobacter pylori.
AB  - Helicobacter pylori NCTC 11637 produces a water-insoluble biofilm when grown
      under defined conditions with a high carbon:nitrogen ratio in continuous culture
      and in 10% strength Brucella broth supplemented with 3 g l-1 glucose. Biofilm
      accumulated at the air/liquid interface of the culture. Light microscopy of
      frozen sections of the biofilm material showed few bacterial cells in the mass of
      the biofilm. The material stained with periodic acid Schiff's reagent. Fucose,
      glucose, galactose, and glycero-manno-heptose, N-acetylglucosamine and N
      acetylmuramic acid were identified in partially purified and in crude material,
      using gas chromatography and mass spectrometry. The sugar composition strongly
      indicates the presence of a polysaccharide as a component of the biofilm
      material. Antibodies (IgG) to partially purified material were found in both sero
      positive and sero-negative individuals. Treatment of the biofilm material with
      periodic acid reduced or abolished immunoreactivity. Treatment with 5 mol l-1
      urea at 100 degrees C and with phenol did not remove antigenic recognition by
      patient sera. The production of a water-insoluble biofilm by H. pylori may be
      important in enhancing resistance to host defence factors and antibiotics, and in
      microenvironmental pH homeostasis facilitating the growth and survival of H.
      pylori in vivo.

PMID- 10063643
TI  - Discrimination of Rhizobium tropici and R. leguminosarum strains by PCR-specific
      amplification of 16S-23S rDNA spacer region fragments and denaturing gradient gel
      electrophoresis (DGGE).
AB  - With the aim of detecting Rhizobium species directly in the environment, specific
      PCR primers for Rh. tropici and Rh. leguminosarum were designed on the basis of
      sequence analysis of 16S-23S rDNA spacer regions of several Rh. tropici, Rh.
      leguminosarum and Agrobacterium rhizogenes strains. Primer specificity was
      checked by comparison with available rDNA spacer sequences in databases, and by
      PCR using DNA from target and reference strains. Sequence polymorphisms of rDNA
      spacer fragments among strains of the same species were detected by denaturing
      gradient gel electrophoresis (DGGE). The specific PCR primers designed in this
      study could be applied to evaluate the diversity of Rh. tropici and Rh.
      leguminosarum by analysing the polymorphisms of 16S-23S spacer rDNA amplified
      from either whole-cell or soil-extracted DNA.

PMID- 10063644
TI  - Comparison of melibiose utilizing baker's yeast strains produced by genetic
      engineering and classical breeding.
AB  - Yeast strains currently used in the baking industry cannot fully utilize the
      trisaccharide raffinose found in beet molasses due to the absence of melibiase
      (alpha-galactosidase) activity. To overcome this deficiency, the MEL1 gene
      encoding melibiase enzyme was introduced into baker's yeast by both classical
      breeding and recombinant DNA technology. Both types of yeast strains were capable
      of vigorous fermentation in the presence of high levels of sucrose, making them
      suitable for the rapidly developing Asian markets where high levels of sugar are
      used in bread manufacture. Melibiase expression appeared to be dosage-dependent,
      with relatively low expression sufficient for complete melibiose utilization in a
      model fermentation system.

PMID- 10063645
TI  - The viability of bifidobacteria introduced into kimchi.
AB  - The viability of bifidobacteria in mul-kimchi, a type of kimchi with added water,
      was investigated under various conditions. When a mul-kimchi preparation was
      inoculated with five strains of Bifidobacterium at a concentration of 10(7) cfu
      ml-1, Bif. longum JK-2 showed the highest viability, maintaining a population of
      10(6) cfu ml-1 after 1 week at 4 degrees C. The influence of NaCl concentration
      and initial pH on viability was further investigated in mul-kimchi inoculated
      with Bif. longum JK-2; NaCl concentrations greater than 3% (w/w) reduced
      viability considerably. In kimchi started with an initial pH of 6.5, the cells
      showed the highest survival. When mul-kimchi containing 2% NaCl (w/w) was
      inoculated with 10(8) cfu ml-1 Bif. longum JK-2, there was a 10-fold reduction in
      viability during 10 d of incubation at 4 degrees C. These results demonstrate
      acceptable levels of the organism in the product, suggesting the possible use of
      selected strains of bifidobacteria in commercial kimchi production.

PMID- 10063646
TI  - Good vision at work.

PMID- 10063647
TI  - Blinded by the light.

PMID- 10063648
TI  - Vision screening.

PMID- 10063649
TI  - Hazardous emissions in the lab.

PMID- 10063650
TI  - Natural and anthropogenic inputs of hydrocarbons to the Strait of Georgia.
AB  - Sediment cores from the Fraser estuary, Vancouver Harbour and Strait of Georgia,
      suspended sediment samples from the Fraser River and sediment grabs from
      Vancouver Harbour have been analyzed for alkanes and parent and alkyl PAHs
      (polycyclic aromatic hydrocarbons). Principal components analysis (PCA) clearly
      distinguishes mixed sources by separating parent PAHs according to molecular
      size, and separating alkyl substituted PAHs from higher plant PAHs. We find the
      Fraser River to be the predominant source for natural and anthropogenic
      hydrocarbons to the Strait of Georgia. The natural hydrocarbon burden from the
      Fraser River is augmented principally by petroleum hydrocarbons and combustion
      PAHs from Vancouver. Contaminated sediments from Vancouver Harbour very likely
      have also been transported to a major ocean disposal site off the Fraser estuary.
      Petroleum alkanes, which dominate Fraser River suspended sediment samples, are
      lost by processes such as dissolution or microbial degradation during transport
      and sedimentation, while PAHs from the river are delivered essentially unchanged
      to sediments in the strait. Hydrocarbon composition undergoes little change with
      depth at a reference location in the Strait of Georgia, indicating that PAH
      inputs have changed very little since the early part of this century. In
      Vancouver Harbour the low rate of sediment accumulation coupled with surface
      mixing has led to the retention of contaminant PAHs within the surface mixed
      layer, while the rapid delivery of sediments from the Fraser River has buried
      contaminant PAHs from historical ocean disposal in the Strait of Georgia.

PMID- 10063651
TI  - Groundwater contamination by azinphos methyl in the northern Patagonic Region
      (Argentina).
AB  - Approximately 30 groundwater monitoring wells, under a fruit production field, in
      the Valley of the Neuquen River (Northern Patagonic, Argentina), to which
      different pesticides have been applied, were sampled eleven times between October
      1995 and March 1997. Azinphos methyl was the main pesticide applied and it was
      detected with the highest frequency in groundwater wells during the period of
      intensive pesticide application in the Southern Hemisphere. Dimethoate,
      methidathion, fosmet, cipermethrin, carbaryl, propoxur, carbofuran, benomyl and
      carbendazim were also detected with lower frequency. The characteristic of the
      area under study was alkaline soil, with an organic matter content below 2.5% and
      texture sandy clay loam. The half life of azinphos methyl in soils was 166.2 days
      in the sun light for horizon A and 194.15 in the dark for horizon B. Leaching of
      azinphos methyl through the different soil horizons was minimum. On the basis of
      our lysimeter laboratory data, in which most of the pesticide was adsorbed into
      the soil column and only small quantities leachate, we inferred that the impact
      of azinphos methyl on groundwater would be minimal. However, field data indicates
      that there is a persistence of azinphos methyl in groundwater during the
      application season.

PMID- 10063653
TI  - Making a difference.

PMID- 10063652
TI  - Hydrogeological investigation of ground water arsenic contamination in south
      Calcutta.
AB  - Typical clinical symptoms of acute arsenic poisoning have been detected in 1000
      residents near a factory in P.N. Mitra Lane, Behala, South Calcutta, located in a
      thickly populated area manufacturing copper acetoarsenite (Paris-Green) an
      arsenical pesticide for the past 25 years. Soil around the effluent dumping point
      of the factory was exceptionally contaminated, with arsenic, copper and chromium
      concentrations of 20,100-35,500 mg kg-1, 33,900-51,100 mg kg-1 and 5300-5510 mg
      kg-1. Arsenic and copper concentrations in bore-hole soils collected up to a
      depth of 24.4 m at the effluent dumping point, decreased with depth. Arsenous
      acid, arsenic acid, methylarsonic acid (MA) and dimethylarsinic acid (DMA) were
      detected in bore-hole soils up to a depth of 1.37 m, after which only inorganic
      arsenical compounds were present. A positive correlation was established between
      arsenic and copper authenticated the Paris-Green waste disposal site as the
      source of contamination. Mechanism of ground water contamination from this
      disposal site had been probed by a systematic hydrogeological survey and the
      arsenic content of the tube-well waters in the surrounding areas. Hydraulic
      conductivity was maximum in the central part. The site for disposal of the
      effluent was a ditch located in the zone of discharge. Sparingly soluble Paris
      Green cumulatively deposited in the waste disposal site is decomposed by micro
      organisms to water-soluble forms and finally percolated to underground aquifers
      along with rain water through the discharge zone. The contaminant is currently
      moving towards WNW with ground water flow and the residents in the direction of
      encroaching contamination are insecure due to penetration of the contaminant.

PMID- 10063654
TI  - A new role for the Bulletin.

PMID- 10063655
TI  - Mumps and mumps vaccine: a global review.
AB  - Mumps is an acute infectious disease caused by a paramyxovirus. Although the
      disease is usually mild, up to 10% of patients can develop aseptic meningitis; a
      less common but more serious complication is encephalitis, which can result in
      death or disability. Permanent deafness, orchitis, and pancreatitis are other
      untoward effects of mumps. Based on data reported to WHO up to April 1998, mumps
      vaccine is routinely used by national immunization programmes in 82
      countries/areas: 23 (92%) of 25 developed countries, 19 (86%) of 22 countries
      with economies in transition (mainly the Newly Independent States of the former
      Soviet Union), and 40 (24%) of 168 developing countries. Countries that have
      achieved high coverage have shown a rapid decline in mumps morbidity.
      Furthermore, in many of these countries, mumps-associated encephalitis and
      deafness have nearly vanished. This review considers the disease burden due to
      mumps; summarizes studies on the immunogenicity, efficacy, and safety of
      different strains of mumps vaccine; and highlights lessons learned about
      implementing mumps immunization in different countries. Countries already using
      mumps vaccine should monitor immunization coverage and establish routine mumps
      surveillance with investigation of outbreaks. Where mumps is targeted for
      elimination, countries need to add a second dose of mumps vaccine for children,
      keeping in mind that the disease may still occur in susceptible adults.

PMID- 10063656
TI  - Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the
      Haemoglobin Colour Scale.
AB  - Anaemia in pregnancy is a common and severe problem in many developing countries.
      Because of lack of resources and staff motivation, screening for anaemia is often
      solely by clinical examination of the conjunctiva or is not carried out at all. A
      new colour scale for the estimation of haemoglobin concentration has been
      developed by WHO. The present study compares the results obtained using the new
      colour scale on 729 women visiting rural antenatal clinics in Malawi with those
      obtained by HemoCue haemoglobinometer and electronic Coulter Counter and with the
      assessment of anaemia by clinical examination of the conjunctiva. Sensitivity
      using the colour scale was consistently better than for conjunctival inspection
      alone and interobserver agreement and agreement with Coulter Counter measurements
      was good. The Haemoglobin Colour Scale is simple to use, well accepted, cheap and
      gives immediate results. It shows considerable potential for use in screening for
      anaemia in antenatal clinics in settings where resources are limited.

PMID- 10063657
TI  - Unrecognized sexually transmitted infections in rural South African women: a
      hidden epidemic.
AB  - Sexually transmitted infections (STIs) are of major public health concern in
      developing countries, not least because they facilitate transmission of human
      immunodeficiency virus (HIV). The present article presents estimates of the
      prevalence, on any given day, of STIs among women in rural South Africa and the
      proportion who are asymptomatic, symptomatic but not seeking care, and
      symptomatic and seeking care. The following data sources from Hlabisa district
      were used: clinical surveillance for STI syndromes treated in health facilities,
      microbiological studies among women attending antenatal and family planning
      clinics, and a community survey. Population census provided denominator data.
      Adequacy of drug treatment was determined through quality of care surveys. Of
      55,974 women aged 15-49 years, a total of 13,943 (24.9%) were infected on any
      given day with at least one of Trichomonas vaginalis, Neisseria gonorrhoeae,
      Chlamydia trachomatis, or Treponema pallidum. Of the women investigated, 6697
      (48%) were asymptomatic, 6994 (50%) were symptomatic but not seeking care, 238
      (1.7%) were symptomatic and would seek care, and 14 (0.3%) were seeking care on
      that day. Only 9 of the 14 women (65%) were adequately treated. STIs remained
      untreated because either women were asymptomatic or the symptoms were not
      recognized and acted upon. Improved case management alone is therefore unlikely
      to have a major public health impact. Improving partner treatment and women's
      awareness of symptoms is essential, while the potential of mass STI treatment
      needs to be explored.

PMID- 10063658
TI  - Use of SoloShot autodestruct syringes compared with disposable syringes, in a
      national immunization campaign in Indonesia.
AB  - Autodestruct syringes can reduce the improper reuse of syringes, which present a
      significant risk in the transmission of bloodborne pathogens in developing
      countries, especially during immunization campaigns owing to the high number of
      injections given per session. SoloShot is an autodestruct syringe, distributed by
      UNICEF, which has been shown to be safer and easier to use than standard
      syringes. This study analyses the accuracy and dose-efficiency of SoloShot,
      compared with disposable syringes, during a national tetanus toxoid immunization
      campaign on the Indonesian island of Lombok. Observation and dose measurements
      revealed that SoloShot syringes delivered more precise and consistent doses and
      15% more doses per vial than disposable syringes. Vaccine savings may partially
      be offset by the higher price of SoloShot. Vaccinators preferred SoloShot,
      describing it as easier to use, faster, and more accurate than the disposable
      syringe. The study indicates that SoloShot is highly appropriate for use in
      immunization campaigns by reducing vaccine wastage and improving injection
      safety.

PMID- 10063659
TI  - Comparison of in vivo and in vitro tests of resistance in patients treated with
      chloroquine in Yaounde, Cameroon.
AB  - The usefulness of an isotopic in vitro assay in the field was evaluated by
      comparing its results with the therapeutic response determined by the simplified
      WHO in vivo test in symptomatic Cameroonian patients treated with chloroquine. Of
      the 117 enrolled patients, 102 (87%) completed the 14-day follow-up, and 95
      isolates obtained from these patients (46 children, 49 adults) yielded an
      interpretable in vitro test. A total of 57 of 95 patients (60%; 28 children and
      29 adults) had an adequate clinical response with negative smears (n = 46) or
      with an asymptomatic parasitaemia (n = 11) on day 7 and/or day 14. The geometric
      mean 50% inhibitory concentration of the isolates obtained from these patients
      was 63.3 nmol/l. Late and early treatment failure was observed in 29 (30.5%) and
      9 (9.5%) patients, respectively. The geometric mean 50% inhibitory concentrations
      of the corresponding isolates were 173 nmol/l and 302 nmol/l. Among the patients
      responding with late and early treatment failure, five isolates and one isolate,
      respectively, yielded a discordant result (in vivo resistance and in vitro
      sensitivity). The sensitivity, specificity, and predictive value of the in vitro
      test to detect chloroquine-sensitive cases was 67%, 84% and 86%, respectively.
      There was moderate concordance between the in vitro and in vivo tests (kappa
      value = 0.48). The in vitro assay agrees relatively well with the therapeutic
      response and excludes several host factors that influence the results of the in
      vivo test. However, in view of some discordant results, the in vitro test cannot
      substitute for in vivo data on therapeutic efficacy. The only reliable definition
      of "resistance" in malaria parasites is based on clinical and parasitological
      response in symptomatic patients, and the in vivo test provides the standard
      method to determine drug sensitivity or resistance as well as to guide national
      drug policies.

PMID- 10063660
TI  - Towards evidence-based health care reform.
AB  - Health care reform in Europe is discussed in the light of the Ljubljana Charter,
      with particular reference to progress made in Estonia and Lithuania.

PMID- 10063661
TI  - The Ljubljana Charter on Reforming Health Care. 18 June 1996.

PMID- 10063662
TI  - Prizes for weight loss.
AB  - A programme of weight loss competitions and associated activities in Tonga,
      intended to combat obesity and the noncommunicable diseases linked to it, has
      popular support and the potential to effect significant improvements in health.

PMID- 10063663
TI  - Animal-to-human organ transplants--a solution or a new problem?
AB  - Xenotransplantation is seen by some mainly as an opportunity and by others mainly
      as a danger. It could help overcome the shortage of organs from human donors, but
      it raises a number of questions, particularly about safety, ethics and human
      nature. This article reviews the progress of research, debate and decision-making
      in this area.

PMID- 10063664
TI  - Measuring the health hazards of tobacco: commentary.

PMID- 10063665
TI  - Smoking and carcinoma of the lung. Preliminary report. 1950.

PMID- 10063666
TI  - Malaria initiative gains momentum.

PMID- 10063667
TI  - AIDS shortens life and dents economic growth across Africa.

PMID- 10063668
TI  - Eradication: lessons from the past.
AB  - The declaration in 1980 that smallpox had been eradicated reawakened interest in
      disease eradication as a public health strategy. The smallpox programme's success
      derived, in part, from lessons learned from the preceding costly failure of the
      malaria eradication campaign. In turn, the smallpox programme offered important
      lessons with respect to other prospective disease control programmes, and these
      have been effectively applied in the two current global eradication initiatives,
      those against poliomyelitis and dracunculiasis. Taking this theme a step further,
      there are those who would now focus on the development of an inventory of
      diseases which might, one by one, be targeted either for eradication or
      elimination. This approach, while interesting, fails to recognize many of the
      important lessons learned and their broad implications for contemporary disease
      control programmes worldwide.

PMID- 10063669
TI  - The principles of disease elimination and eradication.
AB  - The Dahlem Workshop discussed the hierarchy of possible public health
      interventions in dealing with infectious diseases, which were defined as control,
      elimination of disease, elimination of infections, eradication, and extinction.
      The indicators of eradicability were the availability of effective interventions
      and practical diagnostic tools and the essential need for humans in the life
      cycle of the agent. Since health resources are limited, decisions have to be made
      as to whether their use for an elimination or eradication programme is preferable
      to their use elsewhere. The costs and benefits of global eradication programmes
      concern direct effects on morbidity and mortality and consequent effects on the
      health care system. The success of any disease eradication initiative depends
      strongly on the level of societal and political commitment, with a key role for
      the World Health Assembly. Eradication and ongoing programmes constitute
      potentially complementary approaches to public health. Elimination and
      eradication are the ultimate goals of public health, evolving naturally from
      disease control. The basic question is whether these goals are to be achieved in
      the present or some future generation.

PMID- 10063670
TI  - Disease eradication and health systems development.
AB  - This article provides a framework for the design of future eradication programmes
      so that the greatest benefit accrues to health systems development from the
      implementation of such programmes. The framework focuses on weak and fragile
      health systems and assumes that eradication leads to the cessation of the
      intervention required to eradicate the disease. Five major components of health
      systems are identified and key elements which are of particular relevance to
      eradication initiatives are defined. The dearth of documentation which can
      provide "lessons learned" in this area is illustrated with a brief review of the
      literature. Opportunities and threats, which can be addressed during the design
      of eradication programmes, are described and a number of recommendations are
      outlined. It is emphasized that this framework pertains to eradication programmes
      but may be useful in attempts to coordinate vertical and horizontal disease
      control activities for maximum mutual benefits.

PMID- 10063671
TI  - Perspectives from micronutrient malnutrition elimination/eradication programmes.
AB  - Micronutrient malnutrition cannot be eradicated, but the elimination and control
      of iron, vitamin A and iodine deficiencies and their health-related consequences
      as public health problems are currently the targets of global programmes.
      Remarkable progress is occurring in the control of goitre and xerophthalmia, but
      iron-deficiency anaemia (IDA) has been less responsive to prevention and control
      efforts. Subclinical consequences of micronutrient deficiencies, i.e. "hidden
      hunger", include compromised immune functions that increase the risk of morbidity
      and mortality, impaired cognitive development and growth, and reduced
      reproductive and work capacity and performance. The implications are obvious for
      human health and national and global economic and social development. Mixes of
      affordable interventions are available which, when appropriately adapted to
      resource availability and context, are proven to be effective. These include both
      food-based interventions, particularly fortification programmes, such as salt
      iodization, and use of concentrated micronutrient supplements. A mix of
      accompanying programmes for infection control, community participation, including
      education, communication and information exchange, and private sector involvement
      are lessons learned for overcoming deterrents and sustaining progress towards
      elimination.

PMID- 10063672
TI  - Perspectives from the dracunculiasis eradication programme.
AB  - After a slow beginning in association with the International Drinking Water
      Supply and Sanitation Decade (1981-1990), the global Dracunculiasis Eradication
      Programme has reduced the incidence of dracunculiasis by nearly 97%, from an
      estimated 3.2 million cases in 1986 to less than 100,000 cases in 1997. Over half
      of the remaining cases are in Sudan. In addition, the programme has already
      produced many indirect benefits such as improved agricultural production and
      school attendance, extensive provision of clean drinking-water, mobilization of
      endemic communities, and improved care of infants. Most workers in the campaign
      have other responsibilities in their communities or ministries of health besides
      dracunculiasis eradication.

PMID- 10063673
TI  - Perspectives from the global poliomyelitis eradication initiative.
AB  - Ten years after the year 2000 target was set by the World Health Assembly, the
      global poliomyelitis eradication effort has made significant progress towards
      that goal. The success of the initiative is built on political commitment within
      the endemic countries. A partnership of international organizations and donor
      countries works to support the work of the countries. Interagency coordinating
      committees are used to ensure that all country needs are met and to avoid
      duplication of donor effort. Private sector support has greatly expanded the
      resources available at both the national and international level. At the
      programmatic level, rapid implementation of surveillance is the key to success,
      but the difficulty of building effective surveillance programmes is often
      underestimated. Mass immunization campaigns must be carefully planned with
      resources mobilized well in advance. Programme strategies should be simple, clear
      and concise. While improvements in strategy and technology should be continuously
      sought, changes should be introduced only after careful consideration. Careful
      consideration should be given in the planning phases of a disease control
      initiative on how the initiative can be used to support other health initiatives.

PMID- 10063674
TI  - Measles eradication: experience in the Americas.
AB  - In 1994, the Ministers of Health from the Region of the Americas targeted measles
      for eradication from the Western Hemisphere by the year 2000. To achieve this
      goal, the Pan American Health Organization (PAHO) developed an enhanced measles
      eradication strategy. First, a one-time-only "catch-up" measles vaccination
      campaign is conducted among children aged 9 months to 14 years. Efforts are then
      made to vaccinate through routine health services ("keep-up") at least 95% of
      each newborn cohort at 12 months of age. Finally, to assure high population
      immunity among preschool-aged children, indiscriminate "follow-up" measles
      vaccination campaigns are conducted approximately every 4 years. These
      vaccination activities are accompanied by improvements in measles surveillance,
      including the laboratory testing of suspected measles cases. The implementation
      of the PAHO strategy has resulted in a marked reduction in measles incidence in
      all countries of the Americas. Indeed, in 1996 the all-time regional record low
      of 2109 measles cases was reported. There was a relative resurgence of measles in
      1997 with over 20,000 cases, due to a large measles outbreak among infants,
      preschool-aged children and young adults in Sao Paulo, Brazil. Contributing
      factors for this outbreak included: low routine infant vaccination coverage,
      failure to conduct a "follow-up" campaign, presence of susceptible young adults,
      and the importation of measles virus, apparently from Europe. PAHO's strategy has
      been effective in interrupting measles virus circulation. This experience
      demonstrates that global measles eradication is an achievable goal using
      currently available measles vaccines.

PMID- 10063675
TI  - Candidate noninfectious disease conditions.
AB  - Important micronutrient deficiencies in at-risk populations can be addressed
      simultaneously with programmatically cost-effective results. Because of the
      interaction between many micronutrients, this would also be biologically
      effective. With adequate investment and political support, the chances of
      eliminating iodine deficiency as a problem in women of reproductive age and young
      children and of eliminating vitamin A deficiency as a problem in young children
      in the future are high. To eliminate iron deficiency and folic-acid-dependent
      neural tube defects (FADNTDs) in low-income populations, a new set of approaches
      will have to be developed. These same approaches, if successful, could be used to
      tackle other important micronutrient deficiencies.

PMID- 10063676
TI  - Candidate bacterial conditions.
AB  - This article provides background information on bacterial diseases and discusses
      those that are candidates for elimination or eradication. Only one disease,
      neonatal tetanus, is a strong candidate for elimination. Others, including
      Haemophilus influenzae b infection, leprosy, diphtheria, pertussis, tuberculosis,
      meningococcal disease, congenital syphilis, trachoma and syphilis are important
      causes of morbidity and mortality in industrialized and developing countries. For
      all these diseases, eradication/elimination is not likely because of the
      characteristics of the disease and limitations in the interventions.

PMID- 10063677
TI  - Candidate parasitic diseases.
AB  - This paper discusses five parasitic diseases: American trypanosomiasis (Chagas
      disease), dracunculiasis, lymphatic filariasis, onchocerciasis and
      schistosomiasis. The available technology and health infrastructures in
      developing countries permit the eradication of dracunculiasis and the elimination
      of lymphatic filariasis due to Wuchereria bancrofti. Blindness due to
      onchocerciasis and transmission of this disease will be prevented in eleven West
      African countries; transmission of Chagas disease will be interrupted. A well
      coordinated international effort is required to ensure that scarce resources are
      not wasted, efforts are not duplicated, and planned national programmes are well
      supported.

PMID- 10063678
TI  - Candidate viral diseases for elimination or eradication.
AB  - This article discusses the possibilities for elimination or eradication of four
      viral diseases--measles, hepatitis B, rubella and yellow fever.

PMID- 10063679
TI  - Report of the Workgroup on Disease Elimination/Eradication and Sustainable Health
      Development.

PMID- 10063680
TI  - Report of the Workgroup on Noninfectious Diseases.

PMID- 10063681
TI  - Report of the Workgroup on Bacterial Diseases.

PMID- 10063682
TI  - Report of the Workgroup on Parasitic Diseases.

PMID- 10063684
TI  - Conference synthesis and vision for the future.

PMID- 10063683
TI  - Report of the Workgroup on Viral Diseases.

PMID- 10063685
TI  - Folic-acid-preventable spina bifida and anencephaly.

PMID- 10063686
TI  - Iodine deficiency.

PMID- 10063687
TI  - Iron deficiency.

PMID- 10063688
TI  - Vitamin A deficiency.

PMID- 10063689
TI  - Congenital syphilis.

PMID- 10063690
TI  - Diphtheria.

PMID- 10063691
TI  - Haemophilus influenzae type B infection.

PMID- 10063692
TI  - Leprosy.

PMID- 10063693
TI  - Neonatal tetanus.

PMID- 10063694
TI  - Pertussis.

PMID- 10063695
TI  - Trachoma.

PMID- 10063696
TI  - Tuberculosis.

PMID- 10063697
TI  - Chagas disease or American trypanosomiasis.

PMID- 10063698
TI  - Lymphatic filariasis.

PMID- 10063699
TI  - Onchocerciasis.

PMID- 10063700
TI  - Schistosomiasis.

PMID- 10063701
TI  - Hepatitis B virus infection.

PMID- 10063702
TI  - Measles.

PMID- 10063703
TI  - Rubella and congenital rubella syndrome.

PMID- 10063704
TI  - Yellow fever.

PMID- 10063705
TI  - Use of botulinum toxin A in the treatment of hemifacial spasm and blepharospasm.
AB  - BACKGROUND: Hemifacial spasm and blepharospasm are both dystonic disorders. They
      may seriously affect individuals' lifestyle and social activities. In 1990, the
      Food and Drug Administration of the USA approved botulinum toxin A as a
      therapeutic agent in the treatment of hemifacial spasm and blepharospasm. We
      present a therapeutic review of botulinum toxin A in 80 patients in Taiwan.
      METHODS: Fifty-eight patients with hemifacial spasm and 22 with blepharospasm.
      Botulinum toxin A was prepared and injected into the facial and eyelid muscles.
      Patients were monitored every two weeks and classified into four groups
      (excellent, moderate, mild and no improvement) according to the clinical
      improvement scale. Complications were also recorded. RESULTS: A total of 86.2% of
      hemifacial spasm patients and 81.8% of blepharospasm patients had excellent
      improvement on the spasm intensity scale, while 6.8% of hemifacial spasm and 9.0%
      of blepharospasm patients had moderate improvement. The complication rate was low
      and included transient mild facial weakness (5%), ptosis (3.8%), eyelid swelling
      and/or ecchymosis (3.8%), nausea/vomiting (2.5%) and transient severe facial
      weakness (1.3%). CONCLUSION: Botulinum toxin A is an excellent therapeutic agent
      to improve spasm intensity and has a low complication rate.

PMID- 10063706
TI  - Follow-up study in patients with no stone retrieval from the bile duct after
      endoscopic sphincterotomy.
AB  - BACKGROUND: No stones are retrieved from the bile duct in 10-20% of patients with
      suspected common bile duct (CBD) stones after endoscopic sphincterotomy (EST).
      The clinical outcome in these patients remains unclear. This study followed
      patients from whom no stones were retrieved, to discover their clinical outcome.
      METHODS: From October, 1990, to October, 1996, 401 patients with suspected CBD
      stones received EST for stone removal. Only patients from whom no stones were
      retrieved from the bile duct were included in this study. All enrolled patients
      were regularly interviewed and received liver function tests. Sonography,
      computerized tomography, endoscopic retrograde cholangiopancreatography (ERCP),
      and/or intrapapillary biopsy were performed as indicated. RESULTS: Forty-two
      patients were included in this study. The indications for EST included 34 cases
      with filling defects in the common bile duct on ERCP and eight cases with
      suspected impacted stones as seen by imaging studies. After a mean follow-up
      period of 28.6 months (range, 1-61 months), six patients developed biliary
      stones, four had carcinoma of the ampulla of Vater, one was found to have
      intrabiliary growth of hepatocellular carcinoma, and there was no pathologic
      change in 31 cases. Of the six patients with formation of biliary stones, two had
      an intact gallbladder and four had received previous cholecystectomy. Of the four
      patients with ampullary tumors, three were diagnosed by intrapapillary biopsy
      soon after EST, and one was diagnosed nine months later. CONCLUSIONS: Biliary
      problems were found in 26% of patients soon after EST, although no stones were
      retrieved from the bile duct. Regular follow-up is warranted.

PMID- 10063707
TI  - Stroke complicating pregnancy and the puerperium.
AB  - BACKGROUND: The role of nonobstetric factors, such as stroke, in maternal
      mortality has become of increasing importance because maternal deaths resulting
      directly from obstetric causes are decreasing. Strokes contribute to high
      mortality and morbidity, and are severe complications during pregnancy and
      puerperium. The objective of this study was to investigate the maternal outcome
      of patients with complications of stroke during pregnancy and puerperium. The
      causes, incidence and essential management of stroke are also reviewed. METHODS:
      During the 10-year period from January, 1986, to January, 1996, women who
      suffered from stroke during pregnancy, or up to six weeks postpartum, and were
      discharged from our hospital were identified. Stroke was defined as the abrupt
      onset of a focal neurologic syndrome that consisted of hemorrhagic and ischemic
      central nervous system events. All were assessed using computerized tomography or
      magnetic resonance imaging. Neurologists reviewed each case from the medical
      records. RESULTS: Thirteen women who had had a stroke during pregnancy or
      puerperium were identified. Nine of these women had intracerebral hemorrhage and
      four had ischemic strokes. During this 10-year period, approximately 85,321 women
      gave birth at the Mackay Memorial Hospital, and the incidence of stroke was
      approximately 1 in 6,500 pregnancies. Among the nine cases of hemorrhagic
      strokes, three women had preeclampsia and one had gestational diabetes mellitus.
      Mortality from strokes was 38%, and 63% of survivors had residual neurologic
      deficits; 46% of the strokes occurred during the puerperium. CONCLUSIONS: Stroke
      during pregnancy and puerperium causes high mortality and morbidity. Early
      diagnosis and adequate treatment cannot be overemphasized, as prompt and proper
      management is beneficial for outcome. The same meticulous care provided during
      the antepartum and intrapartum periods should be continued into the puerperium.

PMID- 10063708
TI  - Intracranial acute arterial ischemia of the anterior circulation: evaluation with
      three-dimensional time-of-flight magnetic resonance angiography.
AB  - BACKGROUND: Stroke has been the second most common cause of death, after cancer,
      in Taiwan since 1983. The cost of stroke to society in terms of morbidity,
      mortality and economics is profound. Heightened interest in the early diagnosis
      and treatment of acute stroke challenges neuroimagers to optimize available
      modalities and to develop new techniques for the evaluation of cerebrovascular
      disease. The aim of this study was to investigate the effectiveness of magnetic
      resonance angiography (MRA) in conjunction with spin-echo imaging in patients
      with acute brain infarction of the anterior circulation. METHODS: Magnetic
      resonance imaging and three-dimensional Fourier transformed time-of-flight MRA
      studies, performed on 50 patients within one week after the onset of cerebral
      ischemia, were retrospectively reviewed and correlated with clinical records.
      Five of the 50 MRAs were considered nondiagnostic and excluded because of poor
      patient cooperation. RESULTS: In 41 of the 45 cases, the area of infarct
      corresponding to the clinical deficit at the time of study was identified on T2
      weighted spin-echo images. Arterial occlusions or severe stenoses that
      corresponded to ischemic manifestations were identified with MRA in 37 of the 45
      patients. A focal discontinuity with decreased arterial caliber corresponded to
      stenosis and nonvisualization of distal branches represented arterial occlusion.
      MRA provided information for 23 cases not obtained from the MR images.
      CONCLUSIONS: Vascular lesions demonstrated on intracranial MRA show a high
      correlation with infarct distribution. MRA, which provides information adjunctive
      to conventional MR imaging in a majority of cases, is concluded to be an
      important component of the complete evaluation of brain infarction.

PMID- 10063709
TI  - Phylogenetic analysis to document a common source of hepatitis D virus infection
      in a mother and her child.
AB  - BACKGROUND: Spread of hepatitis D virus (HDV) from mother to infant is rare and
      nucleotide evidence to document such transmission is lacking. The aim of this
      study was to screen the children of HDV-infected parents and compare the HDV
      nucleotide sequence between children and parents by phylogenetic analysis.
      METHODS: Fifty-seven children of 28 HDV-infected parents (23 fathers and 5
      mothers, including two couples) were enrolled. HDV genomes from sera of HDV
      infected parents and their children were cloned and sequenced. Comparison and
      phylogenetic analysis of HDV genomes were based on a region from nucleotide 911
      to 1260. The homology to nucleotide sequence among different genotypes was
      estimated by phylogenetic analysis. RESULTS: One of the eight children whose
      mothers were anti-HDV positive was positive for anti-HDV. Mean heterogeneity
      among different HDV clones from a single subject ranged from 0.29% to 1.15%. HDV
      sequences from the mother and her child (referred from southern Taiwan) were
      nearly identical (99.7%), both showed 92.2-93.4% homology with other genotype II
      isolates from north Taiwan and 76.3-77.1% homology with genotype I isolates.
      CONCLUSIONS: Genotype II HDV is most prevalent in Taiwan. There are significant
      variations up to 8% in nucleotide sequence among different genotype II HDV clones
      isolated from patients in northern and southern Taiwan. Phylogenetic analysis
      revealed that HDV clones from the mother and her child form a monophyletic group,
      supporting a common source of infection. Susceptible children of HDV-infected
      mothers should be protected by hepatitis B virus vaccination and active
      education.

PMID- 10063710
TI  - Percutaneous A1 pulley release for trigger digits.
AB  - BACKGROUND: Recently, percutaneous trigger digit release has been reported as a
      safe, effective office procedure. The purpose of this study was to further assess
      the safety and efficacy of this technique. METHODS: From November, 1996, to
      August, 1997, 69 consecutive patients with 71 primary trigger digits were treated
      with percutaneous A1 pulley release. The operations were performed using the tip
      of a 19-gauge needle, mounted on a 3-ml syringe. The mean age of the patients was
      66 years. The mean duration of follow-up was 21 weeks. The patients were
      prospectively classified into two groups according to age, sex, digit involved,
      duration of symptoms and whether or not they had had previous local steroid
      injection. RESULTS: Sixty-three digits were completely free of triggering.
      Residual triggering or inadequate release was found in eight digits at final
      follow-up. The success rate was not associated with sex, age, digit involved,
      duration of symptoms or history of local steroid injection. No major
      complications were found in this study, but minor complications included
      persistent local tenderness in nine digits and subcutaneous hematoma in six
      digits. Risk factors related to persistent local tenderness were female gender
      and trigger thumb. CONCLUSIONS: Percutaneous A1 pulley release is an effective,
      safe and convenient procedure for the treatment of trigger digits.

PMID- 10063711
TI  - Type 1 GM1 gangliosidosis with basal ganglia calcification: a case report.
AB  - This report concerns a 10-month-old boy, admitted to the Veterans General
      Hospital-Kaohsiung with generalized tonic convulsion and aspiration pneumonia. He
      was found to have had developmental regression, progressive hypotonia and
      hepatosplenomegaly since four months of age. Physical examination revealed a
      large head circumference (97th percentile), frontal bossing, depressed nasal
      bridge, hepatosplenomegaly, broad hands and short fingers. Neurologic examination
      showed poor control of eye movement, profound hypotonia, muscle weakness, brisk
      deep tendon reflexes and Babinski's sign. Hypoplasia of the vertebral bodies with
      anterior beaking, wedge-shaped metacarpals, spatulated ribs and a J-shaped sella
      turcica were displayed on bone radiographs. Cranial computerized tomography scans
      showed diffuse brain atrophy, dilated ventricles and calcification of the
      bilateral basal ganglia. Vacuolated lymphocytes were noted in a peripheral blood
      smear. Type 1 GM1 gangliosidosis was diagnosed based on a deficiency of beta
      galactosidase activity. To our knowledge, basal ganglia calcification in type 1
      GM1 gangliosidosis has never been reported in the literature. We suggest that
      type 1 GM1 gangliosidosis be considered in the differential diagnosis of patients
      with an early onset of neurologic decline, organomegaly and basal ganglia
      calcification.

PMID- 10063712
TI  - Arachnoid granulations--computerized tomography and magnetic resonance imaging
      features: a case report.
AB  - A 71-year-old woman had arachnoid granulations found in the straight and
      transverse sinuses on computerized tomography (CT) and magnetic resonance imaging
      (MRI). The arachnoid granulations appeared as low-density masses on CT. They gave
      low signals on T1-weighted MR images and high signals on T2-weighted images.
      Arachnoid granulations are usually of no clinical significance. They have
      characteristic CT and MRI manifestations and should not be mistaken for sinus
      thrombosis or intrasinus tumors.

PMID- 10063713
TI  - Liver abscess secondary to fish bone penetration of the gastric wall: a case
      report.
AB  - An unusual case of liver abscess caused by fish bone perforation of the stomach
      is presented in this report. A 65-year-old woman was admitted to the Far Eastern
      Memorial Hospital for abdominal pain, fever and chills. Physical examination
      revealed anemia and tenderness in the epigastrium. Laboratory data showed
      leukocytosis and abnormal liver function. Computerized tomography of the abdomen
      disclosed a huge abscess in the left lobe of the liver. Exploratory laparotomy
      was performed and a fish bone, 3.7 cm in length, was found perforating the
      stomach with penetration into the left lobe of the liver, resulting in a hepatic
      abscess. Drainage of the liver abscess with removal of the fish bone and simple
      closure of the gastric perforation were performed. The patient recovered
      uneventfully.

PMID- 10063714
TI  - Intracerebral hemorrhage caused by cerebral amyloid angiopathy: a case report.
AB  - Cerebral amyloid angiopathy (CAA) accounts for approximately 10% of spontaneous
      intracerebral hemorrhages (ICH), and typically occurs in the cortex and
      subcortical white matter. It is characterized by the deposition of amyloid
      fibrils in the leptomeningeal, cortical and subcortical arteries. Pathologically,
      amyloid is stained pink with Congo red and shows yellow-green birefringence when
      viewed under polarized light. Although there have been many reports of CAA in the
      literature, it has rarely been described in Taiwan. This is the report of a case
      of a 75-year-old man with ICH caused by CAA. The postoperative course was
      uneventful. The incidence of this disease increases with age. The authors,
      therefore, suggest conducting a brain biopsy and special stain for CAA in each
      operative case of spontaneous ICH, especially in the elderly.

PMID- 10063715
TI  - Serum albumin concentration as a prognostic indicator for acute surgical
      patients.
AB  - BACKGROUND: Whether or not the rapid reduction in serum albumin concentration in
      acute surgical patients without evidence of pre-existing energy deficit
      correlates with outcome has yet to be studied. In this study, we attempted to
      determine whether albumin infusion or nutritional supplementation can improve
      outcome for patients with hypoalbuminemia. METHODS: We retrospectively reviewed
      80 non-calorie-deficient patients newly admitted to the surgical intensive care
      unit of the Veterans General Hospital-Taipei with complete data for serum albumin
      concentration and APACHE II score within 24 hours from August, 1998, to February,
      1994. The relationships between age, sex, diagnosis, reason for intensive care,
      albumin infusion, hyperalimentation, APACHE II score, serum albumin
      concentration, days in intensive care and prognosis within three months were
      analyzed. RESULTS: Univariate statistical analysis showed that the serum albumin
      concentration and APACHE II score correlated well with patient survival (p =
      0.002 and p = 0.025, respectively). Multivariate analysis showed that
      hypoalbuminemia was independently associated with patient outcome (p = 0.003).
      Simple albumin infusion or hyperalimentation for patients with hypoalbuminemia
      did not improve survival. CONCLUSIONS: The results suggest that serum albumin
      concentration appears to be a good prognostic marker for acute surgical patients.
      While decreased serum albumin concentration may also reflect poor nutritional
      status, for patients with moderate to severe hypoalbuminemia due to other causes,
      simple albumin infusion and/or nutritional support did not significantly improve
      survival. Consequently, aggressive treatment of the underlying disease is far
      more important.

PMID- 10063716
TI  - Primary carcinoma of the gallbladder: results of surgery--a retrospective study.
AB  - BACKGROUND: The development of hepatobiliary imaging modalities has resulted in
      earlier detection of gallbladder cancer. This is a retrospective evaluation of
      surgical resection of gallbladder cancer. METHODS: Records of 58 patients with
      gallbladder carcinoma who underwent surgical resection in the past 14 years were
      examined. Patients were staged according to the Nevin system: six had Nevin stage
      I disease; 10, stage II; 9, stage III; four, stage IV; and 24 had stage V cancer.
      Forty-three patients were thought to have resectable lesions. Of these, 14 had
      extended cholecystectomy, 21 simple cholecystectomy, seven simple cholecystectomy
      with biliary drainage and one patient had radical cholecystectomy with
      pancreaticoduodenectomy. Prognoses were analyzed in relation to pathologic
      staging and surgical procedures. RESULTS: The overall one-year and five-year
      survival rates were 50% and 19.2%, respectively. The five-year survival rate for
      Nevin stage I was 100%; for stage II, 60%; stage III, 33%; stage IV, 25% and for
      stage V, 0%. Radical surgery led to a better cumulative survival rate for Nevin
      stages III and IV (p < 0.01) than did simple cholecystectomy. Five Stage II cases
      were treated with simple cholecystectomy but two patients had early metastasis.
      Four stage III patients underwent simple cholecystectomy and three had metastasis
      within one year. CONCLUSIONS: Based on these results, stage III and IV tumors
      require extended procedures for better survival. A high index of suspicion for
      the disease, careful intraoperative examination of the gallbladder specimen and
      earlier, more aggressive treatment may improve patient survival.

PMID- 10063717
TI  - Rheologic determinant changes of erythrocytes in Binswanger's disease.
AB  - BACKGROUND: Binswanger's disease (BD) has been associated with severe
      arteriosclerotic changes in the long perforating arteries and with impaired
      cerebrovascular responsiveness to hypercapnia. Rheology parameters may become
      important factors in regulating cerebral blood flow. The purpose of this study
      was to investigate the changes in rheologic determinants of erythrocytes and to
      discuss the relation of erythrocytes and white matter lesions in this type of
      dementia. METHODS: Twenty-eight patients suffering from BD and a control group
      matched for age, sex and cerebrovascular risk factors were tested for the
      following hemorheologic variables: erythrocyte deformability, erythrocyte
      membrane fluidity, erythrocyte aggregation, plasma viscosity and whole blood
      viscosity. Additionally, red cell membrane metabolic parameters, lipids and
      individual membrane phospholipids, sialic acid (SA) and malondialdehyde (MDA)
      contents, and ATPase activities were measured. RESULTS: A significant decrease in
      erythrocyte deformability, erythrocyte membrane fluidity, membrane
      phosphatidylethanolamine, membrane phosphatidylcholine, membrane SA and membrane
      ATPase activities, and a significant increase in membrane cholesterol,
      cholesterol to total phospholipid ratio, MDA, broad viscosity and erythrocyte
      aggregation were observed in BD patients when compared with those of the matched
      control group. CONCLUSIONS: Changes in erythrocyte membrane parameters,
      especially in phospholipids, can produce serious metabolic disorders and
      influence the rheologic properties of erythrocytes in patients with BD. These
      alterations can contribute to a circulatory slowdown and may lead to worsening of
      the condition of the cerebral white matter in these patients.

PMID- 10063718
TI  - Detection of PAX3-FKHR and PAX7-FKHR fusion transcripts in rhabdomyosarcoma by
      reverse transcriptase-polymerase chain reaction using paraffin-embedded tissue.
AB  - BACKGROUND: Alveolar rhabdomyosarcoma (RMS) is associated with a characteristic
      chromosomal translocation t(2;13)(q35;q14). The genes involved in this
      translocation are paired box (PAX)3 on chromosome 2 and forkhead in RMS (FKHR) on
      chromosome 13. An occasional variant translocation t(1;13)(p36;q14) affecting
      PAX7 and FKHR on chromosomes 1 and 13, respectively, has also been described.
      Chromosomal translocations in RMS are detected using conventional cytogenetic
      analysis, fluorescence in situ hybridization (FISH) or reverse transcriptase
      polymerase chain reaction (RT-PCR) on fresh or frozen tissue samples. We describe
      the results of RT-PCR analysis of PAX3-FKHR and PAX7-FKHR chimeric messages in
      formalin-fixed, paraffin-embedded tissue samples from 17 RMS cases. METHODS: RNA
      was extracted from formalin-fixed, paraffin-embedded RMS tissue. Oligonucleotide
      primers corresponding to the regions of PAX3, PAX7 and FKHR were used for the
      detection of PAX3-FKHR and PAX7-FKHR chimeric messages. A seminested PCR of the
      PCR products was used to increase the sensitivity of detection. The amplified
      fragments were purified and directly sequenced to confirm the specificity of the
      methods. RESULTS: The PAX3-FKHR chimeric message was detected in all three cases
      of alveolar RMS but not in any of the 12 embryonal and two pleomorphic RMS cases.
      The PAX7-FKHR fusion transcript was detected in one case of embryonal RMS.
      CONCLUSIONS: The results indicate that the RT-PCR assay is a reliable method for
      the detection of the PAX3-FKHR fusion transcript of alveolar RMS in formalin
      fixed, paraffin-embedded tissue. This simple method enables pathologists to
      identify chromosomal rearrangements in RMS as a diagnostic aid in cases where
      fresh or frozen tissue is not available.

PMID- 10063719
TI  - Testicular yolk sac tumors in children.
AB  - BACKGROUND: Testicular tumors in children are uncommon, comprising about 1% of
      pediatric malignancies. Yolk sac tumor is the most common malignant testicular
      tumor in children. Because yolk sac tumor in children is rarely seen, its
      treatment has been controversial. We reviewed the records of 15 children with
      testicular yolk sac tumor treated at our hospital in order to evaluate optimal
      management and treatment outcome. METHODS: From February, 1981, to August, 1996,
      15 children with testicular yolk sac tumor were treated. Mean patient age at
      diagnosis was 15.8 months (range, 7-22 months). Fourteen patients presented with
      stage I disease and one presented with stage III disease. Mean follow-up was 88
      months (range, 2-156 months). RESULTS: All 15 patients received radical inguinal
      orchiectomy as initial treatment. Serum alpha-fetoprotein (AFP) concentrations
      were measured in 14 stage I patients preoperatively and were elevated in all of
      them. During follow-up, the one stage III patient died of the disease. Of the
      remaining 14 patients, two (14.3%) had recurrence with elevated AFP at three
      months and 10 months postorchiectomy, respectively. These patients were managed
      with cisplatin-based combination chemotherapy. To date, they are both alive with
      no further recurrence, and AFP concentrations returned to normal after
      chemotherapy. Overall, of the 15 patients with testicular yolk sac tumor, 14
      (93.3%) survived without disease. CONCLUSIONS: Our results suggest that
      testicular yolk sac tumor in children is a tumor with a favorable prognosis.
      Serum AFP concentration is extremely useful in diagnosis and monitoring of
      treatment response. Radical inguinal orchiectomy alone seems adequate for
      patients with stage I disease if serum AFP concentrations return to normal
      postoperatively. Cisplatin-based combination chemotherapy should be administered
      in patients with tumor recurrence or metastasis.

PMID- 10063720
TI  - Inhibitory effects of Woodward's reagent K on carrier-mediated anion transport in
      rabbit intestinal brush border membrane vesicles.
AB  - BACKGROUND: Woodward's reagent K (N-ethyl-5-phenylisoxazolium 3'-sulfonate) is a
      negatively charged reagent that covalently and irreversibly modifies carboxyl
      containing amino acid residues. Under conditions of an outwardly directed
      hydroxide (OH.) gradient (pHin > pHout), folate uptake by jejunal brush border
      membrane (BBM) vesicles is mediated by a folate:OH. exchanger or a
      phenomenologically indistinguishable proton (H+):folate cotransporter. Under
      these pH conditions, Woodward's reagent K rapidly inhibits folate uptake in a pH
      , temperature- and concentration-dependent manner. METHODS: Rabbit BBM vesicles
      were prepared using the divalent cation precipitation method. Vesicle uptake of
      3H-folate was measured by a rapid filtration technique. Radioactivity was gauged
      using a liquid scintillation counter. RESULTS: The initial rate of OH. gradient
      stimulated folate uptake remained linear in the presence or absence of Woodward's
      reagent K, suggesting that Woodward's reagent K inhibition is not secondary to
      more rapid dissipation of the transmembrane pH gradient. Woodward's reagent K
      also inhibited other modes of transport mediated by the folate carrier, 3H
      folate:folate exchanger, ileal sulfate (SO)4(2):OH. exchanger, but neither sodium
      (Na+):glucose, Na+:SO4(2.) nor Na(+):alanine cotransporters, were inhibited by 3
      mM Woodward's reagent K. CONCLUSIONS: The inhibition of intestinal anion
      exchangers by Woodward's reagent K suggests a critical role for carboxyl group-
      containing amino acids in these transport processes.

PMID- 10063721
TI  - Malignant mixed mesodermal tumor presenting as metastatic lymph node
      adenosquamous cell carcinoma: a case report.
AB  - A solitary inguinal lymph node metastasis from a poorly differentiated
      adenosquamous cell carcinoma of unknown origin in a 52-year-old female is
      described. The patient was reported to have had a 2-cm palpable mass in the left
      inguinal area for three years. She had made regular annual clinic visits for Pap
      smears since the age of 45 years. Her last visit was eight months prior to a
      complaint of progressive abdominal distention and dull pain of three months'
      duration. Physical examination showed a huge pelvic mass, and ultrasound and
      magnetic resonance imaging of the abdomen showed a 12-cm complex solid mass on
      the left ovary. The patient underwent a complete excisional biopsy of the left
      inguinal lymph node. Frozen section pathology revealed a poorly differentiated
      adenosquamous cell carcinoma. Exploratory laparotomy immediately followed
      pathologic confirmation of malignancy of the left inguinal lymph node. Complete
      surgical staging including abdominal cytology, total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, infracolic omentectomy, retroperitoneal lymph
      node sampling and excisional biopsy was performed for all suspicious lesions.
      Stage IIIC malignant mixed mesodermal tumor (MMMT) was diagnosed due to positive
      left inguinal lymph node metastasis. However, the retroperitoneal lymph node and
      intra-abdominal cavity did not show spread of the tumors, except those confined
      to the left ovary with adhesion to the cul-de-sac, and sole lymph node metastasis
      in a left inguinal lymph node. Although we could not prove that the left inguinal
      lymph node metastasis had been present for the three years that it was palpable
      without histologic confirmation, we believe that any enlarged inguinal lymph node
      might be the first hint of underlying malignancy in the pelvic area, lower
      extremities or perineal area. In cases of a poorly differentiated carcinoma of
      inguinal lymph nodes of unknown origin, the abdomen should be carefully
      evaluated.

PMID- 10063722
TI  - Hurthle cell carcinoma of the thyroid gland with extensive tumor necrosis: a case
      report.
AB  - Hurthle cell neoplasm of the thyroid gland is rarely associated with tumor
      necrosis. We report a case of Hurthle cell carcinoma of the thyroid gland with
      extensive necrosis. An 82-year-old man had had a right neck mass for more than 10
      years. Approximately two to three weeks before he was hospitalized, this neck
      mass became progressively enlarged. An 131I scan could not demonstrate the right
      lobe of the thyroid gland, while the contralateral lobe was unremarkable. A 99mTc
      sestamibi scan showed increased uptake on the lesion side. Fine needle aspiration
      cytology showed necrosis with macrophages in the initial aspirate, and the
      secondary aspirate appeared suspicious for a Hurthle cell tumor. The patient had
      a total thyroidectomy, and the pathology proved to be Hurthle cell carcinoma with
      tumor necrosis.

PMID- 10063723
TI  - Life-threatening germ cell tumor arising in cryptorchidism: a case report.
AB  - We report a case of life-threatening germ cell tumor in abdominal cryptorchidism.
      A 32-year-old man presented with a three-month history of dyspnea, loss of
      appetite, general weakness and a large abdominal mass. Physical examination
      revealed vacancy of the right scrotal contents. Chest radiograph showed massive
      left pleural effusion. Abdominal ultrasound revealed ascites, right
      hydronephrosis and the presence of an 18 x 15-cm heterogeneous echogenic mass in
      the upper abdomen and right iliac fossa. Abdominal computerized tomography (CT)
      revealed the presence of a large heterogeneous tumor and an enlarged (4 x 4-cm)
      retroperitoneal lymph node. Sonoguided needle biopsy of the abdominal mass
      demonstrated malignant cells of an uncertain type and origin. Serum alpha
      fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) concentrations
      were elevated. Under the diagnosis of metastatic nonseminomatous germ cell tumor
      in abdominal cryptorchidism, the patient received three cycles of cisplatin-based
      combination chemotherapy followed by resection of the abdominal residual
      cryptorchid tumor. Histologically, the tumor showed marked necrosis without
      viable cancer. The patient had remained free of disease for seven months
      following surgery.

PMID- 10063724
TI  - Unusual chromosome 9 variant with an extra G-dark and C-negative segment in the
      short arm, proximal to the centromere: a case study.
AB  - Polymorphic variation of constitutive heterochromatin in human chromosomes is
      commonly seen in clinical cytogenetic analyses. Normal variant can be confirmed
      with C-banding and are generally considered clinically insignificant. However, it
      may be a concern if an unusual variant chromosome is detected in a prenatal
      specimen. We report an unusual chromosome 9 variant with an extra G-dark and C
      negative segment in the short arm, proximal to the centromere. This chromosome 9
      variant has been previously reported in only nine independent families. Whether
      this is a rare variant or an underestimation requires further evaluation. Of note
      is that all probands so far reported in the literature are clinically normal.

PMID- 10063725
TI  - [The German Health Survey. 1997/98].
AB  - The first German Health Survey, a representative study of the health status of
      the population in unified Germany, was started in October 1997. In this project
      which is being carried out by the Robert Koch Institute on behalf of the Federal
      Ministry of Health about 7,200 study participants aged between 18 and 79 are
      going through a medical check-up and are interviewed as to health-relevant
      issues. The German National Health Survey consists of a core survey and
      supplementary modules. These modules are, for the most part, carried out in
      subsamples of the study population. They partially have been designed and co
      financed by cooperating institutions of the RKI. This time, the opportunity given
      to the individual Lander to increase the size of the sample was realized by
      Bavaria. This practised principle of a modular structure and co-financing may be
      regarded as a model and serve as an example for the cost effective implementation
      of such extensive health surveys. As a result, the German National Health
      Examination Survey will yield information enabling the RKI to deliver relevant
      health reports on a federal level and, therefore, to support decisions in health
      policy. The demand for representative population-based data will be met by supply
      of survey data as a file for public use.

PMID- 10063726
TI  - [The German Health Survey 1997/98--examination style].

PMID- 10063727
TI  - [Environmental survey 1997/98].

PMID- 10063728
TI  - [The Nutrition Survey].

PMID- 10063729
TI  - [Folic acid status].

PMID- 10063730
TI  - [The German Health Survey as a pharmaco-epidemiologic instrument].

PMID- 10063731
TI  - [Psychiatric disorders: incidence, psychosocial effects and correlation with
      physical illnesses].

PMID- 10063732
TI  - [The Bavarian Health Survey].

PMID- 10063733
TI  - [Data evaluation in the German Health Survey].

PMID- 10063734
TI  - [External quality control in the German Health Survey 1997/98: concept and
      initial experiences].

PMID- 10063735
TI  - [The Health Survey--outlook].

PMID- 10063736
TI  - Nodules in a nodular liver.

PMID- 10063737
TI  - Arterial pH and arterial oxygenation are not essential for risk stratification in
      perforation peritonitis.
AB  - BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE II)
      scoring system is widely used for assessing the severity of disease and
      prognostication in cases of perforation peritonitis. Investigations like arterial
      pH and oxygenation (PaO2), which are considered important in APACHE II, are not
      available in most hospitals. We therefore attempted to validate a modified APACHE
      II (without arterial pH and oxygenation) in cases of perforation peritonitis.
      METHODS: Fifty consecutive patients with perforation peritonitis admitted in the
      general surgical ward were prospectively analyzed vis-a-vis risk factors and
      mortality according to the modified APACHE II. RESULTS: The mean modified APACHE
      II score of those who died was 15.3 (SD 5.7) as compared to 6.6 (4.7) (p < 0.001)
      in those who survived. As the score increased, mortality rate rose (p < 0.001).
      When the score was greater than 15, mortality was 88.9%; there was 100% mortality
      with score greater than 17. CONCLUSION: The modified APACHE II, excluding
      arterial pH and oxygenation, is simplified, reliable and objective for prediction
      of outcome in perforation peritonitis.

PMID- 10063738
TI  - Incidence of adenomatous hyperplasia in postmortem cirrhotic livers and study of
      cellular proliferative indices by light microscopy.
AB  - BACKGROUND: Adenomatous hyperplasia (AH) or dysplastic nodule in the liver is
      considered a preneoplastic lesion. A wide range in its incidence has been
      reported. AIMS: To study the incidence of AH nodules in autopsy cirrhotic livers
      and to carry out a comparative study of the cellular proliferative indices.
      MATERIALS: Retrospective study of 150 cases with cirrhosis of variable etiology
      at autopsy, over a 15-year period. METHODS: We identified AH on gross examination
      and studied the morphology. We compared cellular proliferative indices in AH
      nodules with other liver nodules by using PCNA monoclonal antibody and AgNOR.
      RESULTS: Alcohol was the commonest etiology (30%), followed by HBsAg positivity
      (38%). Most patients belonged to the 30-60 years age group, with male
      predominance. Sixty of the 150 livers showed AH nodules; there were one to four
      nodules, measuring 6 mm to 50 mm, per liver. 115/122 AH nodules were studied.
      Ordinary AH (OAH) was seen in 104 and atypical AH (AAH) in 11, with malignant
      focus (MF) in four. Associated hepatocellular carcinoma (HCC) was seen in 7
      cases. A gradual increase in the proliferative indices from surrounding
      regenerating nodules (SRN) and OAH to AAH to AAH with MF to HCC was observed. In
      addition, AAH also showed relatively less reticulin fibers. CONCLUSION: The
      incidence of AH was 40%. In addition to the cellular proliferative indices,
      relatively less reticulin fibers could be a distinguishing feature for AAH from
      SRN, OAH and HCC.

PMID- 10063739
TI  - Early changes in esophageal motility after endoscopic variceal sclerotherapy or
      ligation.
AB  - INTRODUCTION: Endoscopic variceal sclerotherapy (EVS) and ligation (EVL) are
      reported to be associated with altered esophageal motility. Most studies have
      been in patients with alcoholic cirrhosis and ascites. AIMS: To study the early
      effect of EVS and EVL in patients with portal hypertension without ascites.
      METHODS: Forty six portal hypertensive patients without ascites underwent
      esophageal manometry 24 h prior to EVS or EVL and within 24 h of two subsequent
      sessions. Nineteen such patients but without prior gastrointestinal bleed were
      studied once as controls. RESULTS: The protocol was completed in 35 patients
      (cirrhosis--16, noncirrhotic portal hypertension--19; 27 men; mean age 36 years).
      Basal midexpiratory lower esophageal sphincter pressure was similar in the study
      group (mean [SD] 20.1 [9.1] mmHg) and controls (17.6 [6.0] mmHg); the pressure
      did not change following EVS or EVL. Amplitude of contractions in the lower 5 cm
      of the esophageal body was similar in the two groups (84.8 [43.1] mmHg and 95.9
      [59.6] mmHg), and decreased (63.6 [34.0] mmHg; p = 0.03) after two sessions of
      variceal therapy. The duration of contraction did not change following
      intervention. Nonperistaltic waves > 2 of 10 swallows were present during the
      baseline study in 9 patients in each group; 13 and 21 patients (p < 0.02 compared
      to baseline) developed them after the first and second sessions of therapy,
      respectively. Percentage of abnormal waves also increased following therapy.
      Thirteen patients developed esophageal ulcers; there was no correlation between
      the presence of ulcers and dysmotility. There was no difference in the changes
      between the EVS and EVL groups, and between patients with cirrhosis and
      noncirrhotic portal hypertension. CONCLUSION: Both EVS and EVL affect esophageal
      motility; these changes do not cause significant esophageal symptoms.

PMID- 10063740
TI  - Role of pulse oximetry during nonsedated upper gastrointestinal endoscopic
      procedures.
AB  - BACKGROUND: Although upper gastrointestinal endoscopy is generally a safe
      procedure, it is known to be associated with arterial oxygen desaturation,
      resulting in rare serious cardio-pulmonary events. OBJECTIVE: To determine the
      severity of oxygen desaturation during nonsedated upper gastrointestinal
      endoscopy and study the effect of various variables on oxygen saturation.
      METHODS: 126 patients underwent nonsedated upper gastrointestinal endoscopy (82
      diagnostic, 44 therapeutic). Arterial oxygen saturation (SaO2) was monitored
      using a pulse oximeter. RESULTS: Baseline SaO2 was mean (SD) 97.8 (1.8%). It
      remained > 95% in 60.2% of patients during the procedure, whereas mild oxygen
      desaturation (SaO2 90%-94%) occurred in 23.7% and severe oxygen desaturation
      (SaO2 < 90%) occurred in 15.8% of patients. Six patients (4.7%) required
      supplemental oxygen administration sometime during the procedure. Desaturation
      occurred in patients undergoing diagnostic and therapeutic procedures but was
      severe in the latter group (p < 0.002). Patients aged more than 60 years (p <
      0.001), hemoglobin < 10 g/dL (p < 0.001), history of smoking (p < 0.001), and
      underlying chronic obstructive airway disease (p < 0.001) were significantly
      related to oxygen desaturation. However, on multivariate analysis, no significant
      correlation was observed with hemoglobin value. CONCLUSION: Therapeutic
      intervention during nonsedated upper gastrointestinal endoscopy, old age, smokers
      and chronic obstructive airways disease are independent risk factors for oxygen
      desaturation. We recommend continuous monitoring of SaO2 in these high-risk
      patients undergoing upper gastrointestinal endoscopy.

PMID- 10063741
TI  - Isoenzyme and molecular characterization of Entamoeba histolytica and Entamoeba
      dispar isolates from symptomatic and asymptomatic subjects.
AB  - AIM: To correlate the clinical features of amebic infections with the
      characteristics of Entamoeba culture isolates of stools. METHODS: Isolates from
      seven irritable bowel syndrome (IBS) patients, four asymptomatic cyst passers
      (ACP) and five patients with invasive amebic disease were subjected to hexokinase
      polyacrylamide electrophoresis (HK-PAGE) and their DNA subjected to restriction
      fragment (RF) analysis of amplified polymerase chain reaction (PCR) products.
      These findings were correlated with anti-amebic serology. Two axenic pathogenic
      strains (HM1:IMSS, NIH:200) and one xenic nonpathogenic strain (SAW1734) were
      used as standards. RESULTS: All isolates from IBS patients as well as ACP had
      slow-moving (nonpathogenic) band pattern, whereas those from patients with
      invasive disease had fast-moving (pathogenic) band pattern on HK-PAGE.
      Serological data using EIA and RF patterns of PCR-amplified genome corroborated
      these results. CONCLUSIONS: Our results support the view that there are two
      species of Entamoeba infecting humans--E. histolytica(pathogenic) and E. dispar
      (nonpathogenic), and HK-PAGE of culture isolates can differentiate between them.

PMID- 10063742
TI  - Insignificant prevalence of antibodies to hepatitis C in a rural area of western
      Maharashtra.
AB  - OBJECTIVE: To determine the age-specific seroprevalence of hepatitis C virus
      (HCV) in a rural population in Maharashtra. METHODS: 1054 serum samples collected
      from apparently healthy persons were tested by recombinant immunoblot assay for
      antibodies against HCV (anti-HCV). Anti-HCV positive samples were tested for HCV
      RNA by nested reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS:
      One man tested positive for anti-HCV; his sample was also HCV-RNA positive.
      CONCLUSIONS: HCV infection is infrequent in this rural area in Maharashtra.

PMID- 10063743
TI  - Epidemiology of digestive tract cancers in India IV. Gall bladder and pancreas.
AB  - Pancreatic cancer is a leading cause of cancer-related deaths in developed
      countries. Gall bladder cancer is very common in South American countries, around
      the Mediterranean and in Japan. A majority of patients with these cancers receive
      only palliative therapy in spite of recent advances in investigation and surgery.
      Their poor prognosis and increasing incidence in India necessitate a better
      epidemiologic approach towards their control. This review is based on
      epidemiological data, publications and abstracts from India. Population-based
      data reveal that the incidence of gall bladder cancer is very high in northern
      Indian cities (5-7 per 100,000 women) and low (0-0.7 per 100,000 women) in
      southern India. The distribution suggests a high-incidence region comprising
      Uttar Pradesh, Bihar, Orissa, West Bengal and Assam. The cancer is twice more
      common in women and is the leading cancer among digestive cancers in women in the
      northern Indian cities of Delhi and Bhopal. There are few analytical data to
      hypothesize why this geographical predisposition. The high incidence is also
      observed in north Indian immigrants to the United Kingdom. The incidence of
      pancreatic cancer is low (0.5-2.4 per 100,000 men and 0.2-1.8 per 100,000 women)
      in most parts of India. Somewhat higher rates are seen in the male urban
      populations of western and northern India. Studies from Kerala support an
      association between tropical pancreatitis and pancreatic cancer. Time trends
      reveal an increase in the incidence of gall bladder and pancreas cancers; the
      increase in the former is alarming. We estimate that the approximate annual
      cancer burden of India in 2001 would include 17,730 cases of gallbladder cancer
      and 14,230 of pancreatic cancer. Multi-center studies are needed to identify
      potentially preventable risk factors associated with gall bladder and pancreatic
      cancer in India.

PMID- 10063744
TI  - T-tube access for endoscopic sphincterotomy: a variant of combined percutaneous
      and endoscopic approach.
AB  - Selective deep cannulation of the common bile duct (CBD), which is essential for
      successful endoscopic sphincterotomy, may not be possible in all patients. Three
      patients with retained CBD stones with T-tube in situ in whom selective deep
      cannulation failed, underwent successful sphincterotomy using a combined
      percutaneous and endoscopic procedure through the T-tube. CBD stones were then
      extracted with a Dormia basket. In situ T-tube can provide percutaneous access
      for combined approach in patients with retained CBD stones in whom endoscopic
      cannulation is not successful.

PMID- 10063745
TI  - Autoimmune sclerosing cholangitis: an overlap syndrome in a child.
AB  - We report an overlap syndrome of autoimmune chronic liver disease and primary
      sclerosing cholangitis in a young girl. This could be the first such report from
      India.

PMID- 10063746
TI  - Richter's hernia: a rare presentation of abdominal tuberculosis.
AB  - Intestinal obstruction due to Richter's hernia has not been reported in abdominal
      tuberculosis. This 21-year-old man with abdominal tuberculosis presented with
      small gut obstruction due to Richter's hernia associated with ascites and patent
      right processus vaginalis (PV). He underwent laparotomy with reduction of
      Richter's hernia and closure of the PV at the right deep inguinal ring.

PMID- 10063747
TI  - Spontaneous rupture of hepatic hydatid cyst causing inferior vena cava
      thrombosis.
AB  - We report a patient with an infected hepatic hydatid cyst, which spontaneously
      ruptured into the inferior vena cava, with resultant thrombosis of the inferior
      vena cava, and left renal, right common iliac and right external iliac veins.

PMID- 10063748
TI  - Pancreatic hydatid cyst.
AB  - A patient with primary hydatid cyst involving the tail of the pancreas and
      treated successfully by distal pancreatectomy is reported. Additionally, we
      performed splenectomy because the spleen was lifted on to the cyst, and
      cholecystectomy for cholelithiasis.

PMID- 10063749
TI  - Superior mesenteric artery syndrome following ileo-anal pouch procedure.
AB  - A rare complication following ileo-anal pouch procedure is the occurrence of
      superior mesenteric artery syndrome. We report a patient with ulcerative colitis
      who developed vascular compression of the duodenum following J-pouch
      construction.

PMID- 10063750
TI  - Synchronous adenocarcinoma and MALT lymphoma of stomach.
AB  - We describe a patient in whom adenocarcinoma and lymphoma occurred simultaneously
      in the stomach. She presented with pain and lump in the epigastrium with history
      of hematemesis. Endoscopy revealed a growth involving the lesser curvature, and
      biopsy showed poorly differentiated carcinoma. Histological examination of the
      gastrectomy specimen showed synchronous diffuse adenocarcinoma with primary
      lymphoma of MALT type. The latter entity is known to be associated with
      Helicobacter pylori infection.

PMID- 10063751
TI  - Double pylorus.
AB  - We report a 55-year-old man presenting with postprandial epigastric pain and
      vomiting. Barium meal study suggested two openings from the stomach to the
      duodenum. Endoscopy revealed double pylorus with chronic duodenal ulcer,
      suggesting the second opening as an acquired one.

PMID- 10063752
TI  - Spontaneous isolated lesser sac hematoma in a patient with hemophilia.
AB  - In patients with hemophilia, hematomas in the mesentery and bowel wall have been
      described uncommonly. The lesser sac is a rare site of spontaneous hemorrhage
      even in patients with bleeding diathesis; only a single case of isolated lesser
      sac hemorrhage has been reported in a hemophiliac patient. We report a similar
      case with no history of trauma. He recovered with administration of factor VIII
      concentrate.

PMID- 10063753
TI  - Segment IV liver cyst with biliary communication following laparoscopic
      deroofing.
AB  - Simple cysts of the liver rarely have a biliary communication. We record the
      development of a biliary communication following laparoscopic deroofing of a
      segment IV simple cyst of liver and document its successful sclerosis with
      tetracycline.

PMID- 10063754
TI  - False negative and false positive cytology in gastric lesions.

PMID- 10063755
TI  - Cecal volvulus: surgical options.

PMID- 10063756
TI  - Ciprofloxacin-resistant Salmonella senftenberg in north India.

PMID- 10063757
TI  - Are H. pylori really absent in dental plaque?

PMID- 10063758
TI  - Immunological studies in hepatitis B carriers.

PMID- 10063759
TI  - Endoscopic removal of trouser hook.

PMID- 10063760
TI  - Carcinoma gall bladder presenting as metastatic lung disease.

PMID- 10063761
TI  - Lumbar intraspinal synovial cysts of different etiologies: diagnosis by CT and MR
      imaging.
AB  - Intraspinal synovial cysts arises from a facet joint and may cause radicular
      symptoms due to nerve root compression. In the present study, three surgically
      and histologically proved cases of synovial cyst of the lumbar spine with
      different etiology are described. The purpose of this report is to illustrate the
      imaging features of various etiologies of intraspinal synovial cysts allowing a
      correct preoperative diagnosis. Review of the literature enables us to say that
      to our knowledge, there is no reported article collecting the imaging findings of
      intraspinal synovial cysts with different etiologies. Only single cases with
      rheumatoid arthritic or traumatic origin have been reported to date. We believe
      that computed tomography and particularly magnetic resonance imaging are the
      methods of choice which provide the most valuable diagnostic information.

PMID- 10063762
TI  - MRI of extrapancreatic gastrinomas.
AB  - Preoperative diagnosis of gastrinoma--especially extrapancreatic gastrinoma--is
      very difficult. At the moment octreotide scintigraphy is considered the method of
      choice to detect gastrinomas. However, MRI may play a major role in the
      diagnostic imaging of gastrinoma.

PMID- 10063763
TI  - [Distension of the inter-facet joints in MRI: and indirect sign of an existing
      underestimation of spondylolisthesis and canal stenosis].
AB  - The authors present two observations of degenerative spondylolisthesis causing
      canal stenosis in which the stenosis was not apparent on MRI examination, due to
      reduction of spondylolisthesis in the supine position. In these cases, MR images
      of the facet joints showed unusual large areas with hypersignal on T2 weighted
      images suggestive of fluid collection. Observation of such images on supine MRI
      images should raise the suspicion of a spondylolisthesis existing on standing
      examination but reduced by the supine position, possibly leading to
      underestimating the canal stenosis.

PMID- 10063764
TI  - Images in clinical radiology. The deep or double lateral femoral notch: indirect
      signs of ACL tear.

PMID- 10063765
TI  - Post-traumatic thrombosis of a segmental branch of the inferior mesenteric vein.
AB  - We report the case of man with post-traumatic thrombosis in a segmental branch of
      the inferior mesenteric vein with secondary venous congestion and ischemia of the
      sigmoid colon. We discuss the current imaging modalities for diagnosing venous
      thrombosis and their relative significance.

PMID- 10063766
TI  - Unusual location of an ovary: ultrasonographic features and surgical correlation.
AB  - We present a case of ectopic ovary in a 5-month-old baby presenting a firm nodule
      in the left labia majora. Ultrasonography was performed and revealed an ectopic
      ovary. The ectopic ovary was surgically returned in adnexial location. We
      describe the typical findings of this entity.

PMID- 10063767
TI  - [The contribution of ultrasonography to various pathologies of the small
      intestine].
AB  - Ultrasonography has progressively become an easily available non expensive
      imaging modality for the study of the small intestine. It has no secondary
      effects and is comforting for the abdominal radiologist. Further, as
      ultrasonography does not require special preparation nor contrast administration
      in the intestine or vascular system, no delay is caused if other imaging
      modalities (such as CT or angiography) have to be performed. This report covers
      the most common pathologic conditions in the small bowel and does not consider
      enteroliths, foreign bodies nor mucoviscidosis.

PMID- 10063768
TI  - Morphologic and quantitative MRI assessment of bone marrow in multiple myeloma
      and chronic lymphocytic leukemia: clinical and prognostic value.

PMID- 10063769
TI  - A comparison of three polytomous item response theory models in the context of
      testlet scoring.
AB  - An alternative to dichotomous scoring of multiple items anchored to a common stem
      is scoring these items as a single polytomous item (testlet scoring). This study
      systematically compared the partial credit model (PCM), the generalized partial
      credit model (GPCM), and the graded response model (GRM) in the context of
      testlet scoring. Data sets included a sample from the fall 1994 administration of
      the SAT I (N = 2,548) and a simulated data set. Theta estimation, information,
      and model fit were analyzed. Correlations among theta estimates ranged from
      0.9748 to 0.9921. The relationship among the information functions of the PCM,
      GPCM and the GRM reflected the discrimination parameter estimates for the latter
      two models. Suggestions are made with regard to model selection.

PMID- 10063770
TI  - The development of a practical and reliable assessment measure for atopic
      dermatitis (ADAM).
AB  - Previous measures of Atopic Dermatitis (AD) have not been adequate for research
      purposes. This paper describes a study conducted in dermatology clinics of the
      Royal Children's Hospital, Melbourne, Australia, to develop a reliable, valid and
      practical measure. A pool of items to describe both site and morphology of AD was
      generated from a literature survey and expert opinion. Selected items were
      incorporated into a measure with each item rated on a four point scale. The
      measure was piloted and revised to a simpler format and called the Atopic
      Dermatitis Assessment Measure (ADAM). Unidimensionality was established.
      Reliability was determined by comparing two doctors blind ratings on 51 patients
      (mean age = 70 months). Agreement varied depending upon site and morphology with
      more agreement on "mild" AD than on "severe" AD. These results imply that
      operational definitions of the scales need to be defined more clearly. The
      measure satisfies the assumptions for a partial credit analysis.

PMID- 10063771
TI  - Competency gradient for child-parent centers.
AB  - This report describes an implementation of the Rasch model during the
      longitudinal evaluation of a federally-funded early childhood preschool
      intervention program. An item bank is described for operationally defining a
      psychosocial construct called community life-skills competency, an expected
      teenage outcome of the preschool intervention. This analysis examined the
      position of teenage students on this scale structure, and investigated a pattern
      of cognitive operations necessary for students to pass community life-skills test
      items. Then this scale structure was correlated with nationally standardized
      reading and math achievement scores, teacher ratings, and school records to
      assess its validity as a measure of the community-related outcome goal for this
      intervention. The results show a functional relationship between years of early
      intervention and magnitude of effect on the life-skills competency variable.

PMID- 10063772
TI  - Alternate forms reliability of the assessment of motor and process skills.
AB  - The purpose of this study is to examine the alternate forms reliability of the
      AMPS (Assessment of Motor and Process Skills) (Fisher, 1997a) where alternate
      forms means different pairs of AMPS tasks. The participants for this study were
      persons selected from the AMPS database who had performed four AMPS tasks. The
      participants varied in age, gender, diagnosis, and level of assistance needed to
      live in the community. The AMPS was administered by trained and calibrated
      occupational therapists according to standardized procedures. The data for the 91
      participants were subjected to 12 many-faceted Rasch analyses to generate ADL
      motor and ADL process ability measures for each task and each set of paired
      tasks. Repeated measures ANOVAs revealed no time effect across the four AMPS
      tasks. Pearson product moment correlations between Tasks 1 and 2 combined and
      Tasks 3 and 4 combined were r = .91 and r = .86 for the ADL motor and ADL process
      scales, respectively. Calculation of the standardized difference (z) revealed
      that no more than 8% of the participants had ADL motor or ADL process ability
      measures that differed significantly between observations once we accounted for
      real differences in a persons performance; 80% of the paired ADL motor and ADL
      process ability measures remained stable within +/- 0.5 logits when the
      participants performed two tasks. The AMPS ADL motor and ADL process scales can
      be used reliably in clinical practice and for research purposes.

PMID- 10063773
TI  - Teacher receptivity to a system-wide change in a centralized education system: a
      Rasch measurement model analysis.
AB  - The Education Department of Western Australia has implemented a new system called
      Student Outcome Statements, by trial in 1995/1996, then an a voluntary basis from
      1997, with the intention of making it mandatory after 2001. The system describes,
      in order, the outcomes that students are expected to achieve in eight broad
      learning areas. The study has three aims. One, to create a scale for teacher
      receptivity to the use of Student Outcome Statements, based on eight orientations
      to receptivity: evaluative attitudes, behavior intentions, feelings towards
      Student Outcome Statements compared to the previous system, the benefits of the
      new system, support from significant others, alleviation of concerns,
      collaboration with other teachers, and involvement in decision-making. Two, to
      analyze the psychometric properties of the scale using the Extended Logistic
      Model of Rasch (Andrich, 1988; Rasch, 1960/1980) with the computer program RUMM
      (Andrich, Sheridan & Luo, 1997). Three, to provide advice to decision-makers
      about how better to implement the system of Student Outcome Statements.

PMID- 10063774
TI  - Distractors--can they be biased too?
AB  - Numerous work has been done on item bias and differential item functioning.
      Although there is some research on distractor analysis, no detailed study has
      been attempted to examine the way distractors in an item function, with regards
      to comparing distractor performance. This paper examines how distractors function
      differentially and compares various methods for identifying this. The Pearson chi
      square, likelihood ratio chi-square and Neyman weighted least squares chi-square
      tests are some of these methods. Possible causes of distractor bias are discussed
      with illustrations from a physics problem-solving scale.

PMID- 10063775
TI  - Three-dimensional movement of the foot during the stance phase of walking.
AB  - This study presents research on typical movement of the rearfoot during walking.
      The data demonstrate the global nature of foot pronation and supination during
      gait. Study participants (N = 153) walked along a walkway while the angular
      displacement of the calcaneus, navicular, and first metatarsal relative to the
      tibia was measured; three-dimensional movement patterns for all three bones were
      very similar. This study provides additional information on how the foot
      functions during walking. This information should help to define and refine
      clinical management strategies for treating foot dysfunction.

PMID- 10063776
TI  - Heel pain in children. Diagnosis and treatment.
AB  - Heel pain in children is common, and its evaluation is challenging. Medical
      history and physical examination may be unrevealing owing to children's limited
      communication skills. Often, advanced laboratory and imaging studies are required
      to make an accurate diagnosis. The most common causes of heel pain in children
      are apophysitis, enthesopathy, and overuse syndromes such as tendinitis. Juvenile
      rheumatoid arthritis is relatively uncommon. In very active children, occult
      fractures must also be evaluated. Pain unrelated to activity may indicate tumors,
      infection, or congenital problems. In general, heel pain in children is treated
      nonoperatively. For fractures in particular, children are less likely than adults
      to receive surgical treatment.

PMID- 10063777
TI  - The effects of increasing heel height on forefoot peak pressure.
AB  - The purpose of this study was to determine the effect of increasing heel height
      on peak forefoot pressure. Thirty-five women were examined while wearing sneakers
      and shoes with 2-inch and 3-inch heels. An in-shoe pressure-measurement system
      was used to document the magnitude and location of plantar peak pressures.
      Pressure under the forefoot was found to increase significantly with increasing
      heel height. As the heel height increased, the peak pressure shifted toward the
      first metatarsal and the hallux. The reproducibility of data obtained with the in
      shoe pressure-measurement system was tested in five subjects; the data were found
      to be reproducible to within approximately 3% of measured pressures.

PMID- 10063778
TI  - Long-term follow-up of heel spur surgery. A 10-year retrospective study.
AB  - A comparative retrospective study of 48 open heel spur surgeries and 20
      endoscopic plantar fasciotomies was conducted involving 59 patients over a 10
      year period. There was a significant reduction in heel pain at the time of follow
      up (average, 3 years) for both groups. Overall, 85% of procedures were associated
      with patient satisfaction with the results, and patients said that they would
      recommend heel spur surgery for relief of severe heel pain in 94% of cases.
      Factors influencing the postoperative outcome, such as duration of preoperative
      symptoms, extent of conservative care, and obesity, are discussed.

PMID- 10063779
TI  - Retrospective review of endoscopic plantar fasciotomy. 1994 through 1997.
AB  - In the September 1996 issue of the Journal of the American Podiatric Medical
      Association, the authors published a retrospective review of their experiences
      with and results of plantar fasciotomy from 1992 through 1994. Since then,
      patients who underwent endoscopic plantar fasciotomy from 1994 through 1997 have
      been reviewed by utilizing materials and methods identical to those used in the
      original study. This article provides an update of the results of endoscopic
      plantar fasciotomy and compares them with the results described in the 1996
      study.

PMID- 10063780
TI  - Planovalgus foot deformity. Current status.
AB  - Flatfoot may be classified as pathologic or physiologic. Pathologic flatfoot is
      often characterized by stiffness of the foot, causes disability, and requires
      treatment. Physiologic flatfoot is a normal variation; it causes no disability
      and tends to improve with time. Physiologic flatfoot is most common in
      individuals who are loose-jointed, are obese, or usually wore shoes during
      childhood. Treatment of children with physiologic flatfoot with orthoses or shoe
      modifications not only is ineffective but is uncomfortable and embarrassing for
      the child and is associated with lowered self-esteem in adult life.

PMID- 10063781
TI  - Limb salvage with Chopart's amputation and tendon balancing.
AB  - For several decades, Chopart's amputation has met with some skepticism owing to
      reports of significant equinus deformity developing soon after the procedure is
      performed. However, with appropriate tendon balancing, which generally includes
      anterior tibial tendon transfer and tendo Achillis lengthening, this level of
      amputation is often more functional than slightly more distal amputations, such
      as Lisfranc or short transmetatarsal amputations. The authors offer a rationale
      for this observation, which includes a discussion of the longitudinal and
      transverse arch concept of the foot. This concept dictates that the shorter the
      midfoot-level amputation, the more likely the patient is to develop an
      equinovarus deformity, thus exposing the fifth metatarsal base and cuboid to
      weightbearing stress and a high risk of ulceration. Chopart's amputation, in
      eliminating the cuboid, often obviates the potential varus deformity and thus can
      have a more acceptable long-term result.

PMID- 10063782
TI  - Life cycle of the African-American male: improving survival outcomes.

PMID- 10063783
TI  - Southern states have largest number of AIDS cases.

PMID- 10063784
TI  - Relative rates of AIDS among racial/ethnic groups by exposure categories.
AB  - The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated
      among racial/ethnic populations using Centers for Disease Control and Prevention
      HIV (human immunodeficiency virus)/Surveillance reports assuming that
      racial/ethnic distributions reflect that of the US Census Data from 1990. For
      comparison, a rate of 1 was assigned to whites in each calculation. The overall
      relative rates were whites--1, African Americans--4.7, Hispanics--3,
      Asian/Pacific Islanders--0.4, and Native Americans--0.5. Acquired
      immunodeficiency syndrome surveillance data show higher rates of AIDS for African
      Americans and Hispanics compared with whites, Asians/Pacific Islanders, and
      Native Americans. The relative rates for African Americans and Hispanics compared
      with whites were highest for injecting drug users, heterosexual contact, and
      pediatric patients. These results led us to explore possible explanations for
      increased AIDS reporting in African Americans and Hispanics. We then explored
      available national datasets regarding those variables. The analyses indicate that
      variables such as access and receptivity to HIV prevention and treatment efforts,
      race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic
      status, and substance abuse interact in a complex fashion to influence HIV
      transmission and progression to AIDS in affected communities.

PMID- 10063785
TI  - Should a history section be included on the National Youth Sports Program
      preparticipation physical examination?
AB  - The National Youth Sports Program (NYSP) is an annual event sponsored by the
      National Collegiate Athletic Association that provides structured sports and
      enrichment programs to youth of low socioeconomic status. As part of the program,
      youths undergo a free medical examination that uses a physical examination
      checklist but does not include a section on medical history. To determine what
      additional information a medical history would provide, a history form was used
      in conjunction with the regular preparticipation examination for participants in
      the 1996 NYSP at the North Carolina Agricultural and Technical State University.
      The history form provided information such as family history of sudden death,
      personal history of asthma or bone injury, and whether participants took
      medications or used corrective lenses. Seventy-nine percent of the completed
      history forms documented a positive response to at least one question. Of these,
      only 5% had physical findings on examination. Conversely, 15% of participants had
      physical findings that were not reported on the history form. Because much of
      what is discovered by a medical history often is not found on physical
      examination and because history information can be used to prevent the occurrence
      of an accident or illness, this study suggests that the use of such a form is
      beneficial in providing a more comprehensive screening.

PMID- 10063786
TI  - Actinomyces and nocardia infections in immunocompromised and nonimmunocompromised
      patients.
AB  - A retrospective survey of nocardia and actinomyces infections in five local
      hospitals was conducted over a 3-year period in El Paso, Texas, a border city, in
      the southwestern United States. The medical records of 42 patients with suspected
      nocardiosis or actinomycosis were reviewed. One patient was diagnosed with
      actinomyces and 12 patients with nocardia. Microbiological data included
      morphologic characteristics, biochemical profile, and susceptibility testing.
      Predisposing factors included leukemia, renal insufficiency, renal transplant,
      and lymphoma. No predisposing factors were found in 67% (n = 8) of patients
      (including the patient with actinomycosis). Twenty-three percent (n = 3) of
      patients had disseminated disease without evidence of underlying disease or
      immunosuppression. The mortality and morbidity of these infections appeared to be
      low.

PMID- 10063787
TI  - Low-dose combination therapy as first-line hypertension treatment for blacks and
      nonblacks.
AB  - To assess the efficacy and safety of bisoprolol/6.25-mg hydrochlorothiazide
      (HCTZ), amlodipine, and enalapril in black and nonblack patients, data from two
      comparative studies were pooled and subgroup analyses performed. Both studies had
      similar designs and included all three active treatments. The second study also
      included a placebo group. Subjects (n = 541) with a sitting diastolic blood
      pressure of 95-114 mmHg were titrated to achieve a diastolic blood pressure < or
      = 90 mmHg. The studies included 114 blacks and 427 nonblacks. Results of an
      intention-to-treat analysis of mean change from baseline after 12 weeks of
      treatment showed the following: 1) blood pressure was significantly lowered by
      all three active drugs compared with baseline or placebo; 2) in blacks,
      bisoprolol/6.25-mg HCTZ resulted in significantly greater reductions of systolic
      and diastolic blood pressure than enalapril or placebo, but was not significantly
      different from amlodipine; 3) in nonblacks, bisoprolol/6.25-mg HCTZ resulted in
      significantly greater reduction of diastolic blood pressure than amlodipine,
      enalapril, or placebo. The placebo-corrected change in blood pressure was greater
      for blacks than whites on the bisoprolol/6.25-mg HCTZ combination, but this was
      not statistically significant. Bisoprolol/6.25-mg HCTZ controlled diastolic blood
      pressure to < or = 90 mmHg in significantly more patients than enalapril or
      placebo in blacks and nonblacks. The difference in control rates was not
      significant versus amlodipine. The incidence of drug-related adverse events was
      similar between treatments; however, bisoprolol/6.25-mg HCTZ had a lower
      discontinuation rate due to lack of blood pressure control or adverse experiences
      in both blacks and nonblacks.

PMID- 10063788
TI  - Cytochemistry and ultrastructure of canine myocardium undergoing global ischemia
      and reperfusion injury.
AB  - In order to highlight severity of myocardial injury during the course of global
      ischemia and reperfusion, cytochemistry of glycogen and succinate dehydrogenase
      (SDH) as well as hematoxylin and eosin staining (H & E) and electron microscopy
      were observed in canine myocardium. Seven mongrel dogs were selected for
      reperfusion injury after global ischemia in this study. Myocardial biopsies were
      taken from the anterior wall of the left ventricle (a) after cardiopulmonary
      bypass (the first biopsy); (b) at the end of the aortic crossclamp (the second
      biopsy); and (c) 30 minutes after crossclamp removal (the third biopsy). All
      biopsies were cytochemically assessed, and the latter two, for electron
      microscopic studies. The averages of myocardial necrotic rate and surface to
      volume ratio of myocardial mitochondria were calculated under electron microscopy
      and in electron microscopic slices, respectively. Myofibrillae were of normal
      morphology in the first biopsy; in wave-shape and partly vacuolated, with large
      and deformed nuclei in the second one; and in wave-shape and severely vacuolated
      in the third one, in H & E. Glycogen granules were variously stained in moderate,
      weak and intensive positive reactions in the three biopsies respectively in
      glycogen staining. SDH was stained in intensive, weak, and moderate positive
      reactions in three, respectively. By electron microscopy, Z bands twisted
      severely, and local dissolution of cristae and matrix occurred in a minority of
      the mitochondria in the second biopsy; and majority of the Z bands in necrotic
      region had disappeared, the myofibrillae were obscure and patchily dissolved.
      Clustered and deformed mitochondria could be found in the third biopsy.
      Significant difference could be noted between the averages of the second and
      third biopsies (14.88 +/- 3.09% vs. 60.25 +/- 8.55%, p < 0.001). The surface to
      volume ratio of the ischemic mitochondria was much bigger than that of the
      reperfused (3.95 +/- 1.09 micron-1 vs. 2.77 +/- 0.93 micron-1, p = 0.041).
      Myocardial injury was more severe in reperfusion than in ischemia myocardium.
      There were correlations between histobiochemical and ultrastructural alterations
      in damaged canine myocardium.

PMID- 10063789
TI  - A delivery circuit for normothermic reperfusion model.
AB  - In order to facilitate the introduction and assessment of Injectio Radix Ginseng
      Compositae in normothermic reperfusion model, a simplified delivery circuit is
      described herein. The circuit added mainly a venous reservoir collecting Injectio
      Radix Ginseng Compositae with cardiopulmonary bypass. Injectio Radix Ginseng
      Compositae was pumped into the ascending aorta of the animal after mixing with
      cardioplegia in the venous reservoir. The circuit was acceptable in terms of
      price by most inland medical laboratories. Perfusion as well as biochemical
      results monitored were satisfactory. Significant difference was noted between the
      average damage rates of the reperfused myocardial mitochondria in groups by
      ultrastructural analysis (70.12 +/- 2.56% vs. 25.33 +/- 17.62%, p = 0.023). No
      complications associated with perfusion technique occurred in either group. The
      circuit could offer a constant arterial perfusion, and was proved to be simple,
      safe and effective in cohort.

PMID- 10063790
TI  - Development of adenoids: a study by measurement with MR images.
AB  - Magnetic resonance (MR) imaging, which is able to demonstrate the actual size of
      adenoids by differentiating them from other soft-tissue structures, can be
      effectively used to study the normal development of adenoids. To assess the
      normal development of adenoids and to understand their role in the nasopharyngeal
      airway compromise, the adenoids of 290 children who had MR examination for other
      reasons were measured by midsagittal T1-weighted spin-echo MR image. The maximal
      thickness of adenoids (A), anteroposterior depth of the nasopharynx (N) and the
      adenoid-nasopharynx (A/N) ratios were obtained using this method. The results
      showed that of the infants under the age of 3 months only 2 out of 11 adenoids
      (18%) could be identified. By 4 months of age, adenoids could be identified in 6
      of 8 infants (75%). After 5 months of age, all adenoids were well demonstrated by
      MR imaging. The adenoids developed rapidly during infancy and reached a plateau
      between 2- and 14 years of age with a mean thickness ranging from 10.7 to 12.2
      mm. Finally, the adenoids regressed rapidly after 15 years old. The A/N ratios,
      which could be used to assess the airway compromise, had a plateau between 2- and
      7 years of age. After that, with the steady growth of the nasopharynx, the
      possible role of adenoid in airway compromise will become increasingly less
      significant in later childhood.

PMID- 10063791
TI  - The hemodynamic changes of gastroduodenal regional blood flow after Helicobacter
      pylori eradication in patients with duodenal ulcer scar.
AB  - Duodenal ulcer (DU) is frequently accompanied by Helicobacter pylori (Hp)
      infection and associated with the imbalance of aggressive factors and defensive
      factors. To investigate the possible relationship between Hp and regional gastric
      blood flow, 26 endoscopically proved DU (scar stage) and Hp infection patients
      were included and received triple therapy (colloid bismuth subcitrate 120 mg qid
      for 4 weeks, amoxicillin 500 mg qid for 2 weeks and metronidazole 250 mg tid for
      2 weeks). Regional gastroduodenal blood flow (RGDF) was measured at DU scar area
      and antrum lesser curvature site by laser Doppler flowmetry during endoscopic
      examination, before and one month after triple therapy. In 22 patients with Hp
      eradication the RGDF was significantly elevated at antrum lesser site after
      triple therapy (p < 0.05) but there was no difference at DU scar area. However,
      in 4 patients without Hp eradication no difference of RGDF in these two points
      was found. Therefore, Hp appears to have direct effects on gastric
      microcirculation.

PMID- 10063792
TI  - Discordance between uterine cervical cytology and biopsy: results and etiologies
      of a one-year audit.
AB  - To investigate the etiologies of discrepancies between cervicovaginal smear and
      corresponding cervical biopsy results, a total of 15,474 cervicovaginal smears
      were sampled in a one-year period. Among these, 427 patients were diagnosed with
      atypical squamous cells of undetermined significance (ASCUS), dysplasia, or
      malignancy. The screen positive rate was 2.8%. All of the positive cases had
      histologic follow-up. Forty-nine of the 427 patients had a discrepancy of at
      least two grades (the grades are divided to negative, ASCUS, mild dysplasia,
      moderate dysplasia, severe dysplasia and invasive carcinoma), between the
      cytologic and histologic diagnoses. The discrepancy rate was 11.5%. Ten of these
      discrepant cases had poorly-preserved slides or a not definitely final diagnosis.
      A total of 39 cases (79.6%) of discrepancy were reviewed in this study. In thirty
      (77%) of the 39 discrepant cases, the errors were cytologic and in 9 cases (23%)
      the errors were histologic. Cytologic error was the major cause of cytohistologic
      discrepancy. The etiologies of cytohistologic discrepancy included: cytologic
      interpretation error, 17 cases (44%); cytologic sampling error, 10 cases (25%);
      biopsy sampling error, 6 cases (15%); cytologic screen error, 3 cases (8%); and
      biopsy interpretation error, 3 cases (8%). The major etiology of cytohistologic
      discordances was cytologic interpretation error. In this retrospective study, we
      determined the etiologies of cytohistologic discrepancies. This information can
      be useful for improving diagnostic accuracy and the quality of patient care.

PMID- 10063793
TI  - Clinical experiences of germ cell tumor in cryptorchid testis.
AB  - The increased risk of malignancy occurring in the cryptorchid testis is well
      established. In order to investigate the management and outcome of germ cell
      tumor in cryptorchid testis, we retrospectively reviewed the records of 11
      patients with cryptorchid tumor treated at our hospital between January 1973 and
      December 1996. Mean patient age at diagnosis was 47.6 years (range, 22-80). Of
      these patients, 3 were found in the inguinal area and 8 in the abdomen. Six
      occurred in the right cryptorchid testis and 5 in the left. Four patients
      presented with stage I disease, 4 with stage II, and 3 with stage III. Median
      follow-up period was 48.0 months (range 1-163). All 3 inguinal cryptorchid tumors
      and 6 of 8 abdominal cryptorchid tumors were seminoma. The remaining 2 abdominal
      cryptorchid tumors were nonseminomatous germ cell tumor. Of the 3 patients with
      inguinal cryptorchid seminomas, 2 with stage I disease were treated with
      prophylactic radiotherapy to nodal areas and 1 with stage III disease was treated
      with chemotherapy. Eight patients with abdominal cryptorchid tumors were treated
      with multidisciplinary approaches, including radiotherapy, cisplatin-based
      combination chemotherapy, and surgery. The overall survival rate for patients
      with inguinal and abdominal cryptorchid tumor was 81.8%. Two patients with stage
      III disease died during treatment and the remaining 9 patients are still alive
      without evidence of disease.

PMID- 10063794
TI  - The presentation of serum lipids and uric acid in cerebral ischemia.
AB  - In this study, we examine the relationship between serum lipids and uric acid in
      nonembolic cerebral ischemia (NECI) patients. The serum level of total
      cholesterol (TC) and uric acid increased significantly in male, while TC and
      triglyceride in female patients. The increase of TC was more significance in
      female patients. There was no correlation between serum lipids and uric acid in
      NECI patients or controls, but a significant correlation between triglyceride and
      uric acid was present in diabetic patient. These findings suggest that lipids and
      uric acid are essential risk factors for cerebral ischemia in our population.
      Although there is no association of their metabolism, their parallellic
      abnormality in diabetic NECI individuals indicates that some possible factors
      changing in diabetics can influence the metabolic pathway of both lipid and uric
      acid, which may promote each other for atherogenesis in diabetics.

PMID- 10063795
TI  - Psychosocial aspects of Taiwanese postpartum depression phenomenological
      approach: a preliminary report.
AB  - To understand how Taiwanese women experience postpartum depression, a
      phenomenological study was conducted. A purposive sample of six mothers
      participated in the present study. All the subjects' interviews were tape
      recorded and then transcribed. The transcription of each subject's oral
      description of postpartum depression experience was analyzed using Colaizzi's
      phenomenological methodology. Three categories, with ten themes, were derived
      from the analysis. The first category is unbalanced role-enacting. It includes
      these four themes: (1) the discrepancies in the husband-wife relationship; (2)
      the shadowy position of a daughter-in-law; (3) the incompetence as a mother; and
      (4) the dilemma of a woman's identity. The second category is fragmented time
      space representation. The themes included are: (5) cultural bondage; (6) loss of
      ideals; and (7) reinterpretation of family history. The third category is the
      uneasy self. It contains the themes of: (8) psychological disability; (9) sense
      of self-dissatisfaction; and (10) the notion or behavior of destruction.

PMID- 10063796
TI  - A huge pancreatic cystic adenoma misdiagnosed as an ovarian cyst.
AB  - Pancreatic cyst mimicking an ovarian cyst ultrasonographically has not yet been
      reported. We report an elderly woman with such a huge pancreatic cyst whose
      initial presentation was low abdominal pain. Ultrasound showed a hypoechoic cyst
      measuring 13.6 x 13.2 x 11.8 cm occupying pelvic cavity. She received laparotomy
      under the impression of ovarian cyst. Interestingly, the cyst was found to have
      originated from the pancreas. Total cyst excision was performed and pathologic
      report was pancreatic microadenoma. The patient's postoperative course was
      unremarkable.

PMID- 10063797
TI  - Bilateral gluteal dystrophic calcification--a case report.
AB  - Abnormal deposits of calcium in the injured and necrotic tissue (dystrophic
      calcification) are not considered to be rare conditions in human pathologic
      records. We report a severe case of bilateral gluteal calcification that has not
      often been found in the literature. It was caused by multiple intramuscular
      and/or subcutaneous injections. The multiple lumps along with the chronic
      unhealed fistula over the gluteal regions were successfully treated by carbon
      dioxide laser without recurrence. The pathogenesis of variable possibilities were
      reviewed and discussed.

PMID- 10063798
TI  - The fluorescent probe prodan characterizes the warfarin binding site on human
      serum albumin.
AB  - The fluorescent probe Prodan (6-propionyl-2-dimethyl-aminonaphthalene) binds with
      high affinity to human serum albumin (HSA). The spectral characteristics of the
      Prodan bound to the protein are very different from the free Prodan in solution.
      These differences allowed the spectra to be deconvoluted into log-normal bands in
      order to quantify the bound and unbound ligand and to calculate the binding
      constant at different temperatures. From such temperature dependence, we found
      the binding to be exothermic with a van't Hoff enthalpy of -22.8 kJ mol-1.
      Thermodynamic analysis suggests that the interaction may be mainly caused by
      hydrophobic forces and electrostatic interactions. The above analysis of the
      spectra and the measures of the fluorescence polarization during the successive
      presence of six specific drugs suggest that the Prodan binding site corresponds
      with the warfarin binding site on HSA, whereas under the present experimental
      conditions the other characteristic binding sites of HSA were not affected. Thus,
      this fluorescent probe provides a rapid and simple means for the characterization
      of a specific binding site on HSA and also for detecting potential or nonspecific
      drug-protein interactions.

PMID- 10063799
TI  - Alterations of hairless mouse skin exposed to chronic UV irradiation and its
      prevention by hydrocortisone.
AB  - Ultraviolet-induced alterations of skin were investigated in a murine animal
      model. Groups of hairless mice were exposed to UV (black light, lambda max 352
      nm; UV distribution: 300-310 nm, 0.9%; 310-320 nm, 2.0%; 320-420 nm, 97.1%) for
      20 weeks at a dose of 16.3 J/cm2 five times weekly on weekdays. At the end of 20
      weeks irradiation, the dorsal skins were biochemically and histologically
      examined. Ultraviolet caused remarkable increases in amounts of hyaluronan,
      chondroitin sulfates and dermatan sulfates in skin (microgram/cm2).
      Interestingly, a significant change in a collagen content (hydroxyproline,
      microgram/g of dry powder) caused by UV irradiation was not observed, whereas the
      amount of collagen (hydroxyproline, microgram/cm2) increased remarkably.
      Histologically, no distinguishable thickening was observed in both upper dermis
      and lower dermis, but thickening of the epidermis was observed. Furthermore, the
      histological study indicated that UV irradiation caused a disappearance of crowds
      of adipocytes, alternative appearance of numerous fibroblasts and accumulation of
      collagen bundles and hyaluronan in lower dermis. Hydrocortisone, an anti
      inflammatory agent, prevented both the fibrosis of lower dermis and the
      accumulation of the extracellular matrix components. Based on these results, it
      seems reasonable that UV penetrates into the lower dermis and causes fibrosis
      there, resulting from the inflammatory responses.

PMID- 10063800
TI  - Chronology of the apoptotic events induced in the K562 cell line by photodynamic
      treatment with hematoporphyrin and monoglucosylporphyrin.
AB  - Photodynamic treatment of promyelocytic K562 cells in the presence of a
      monoglucosylporphyrin or hematoporphyrin leads to a sequence of events recognized
      as hallmarks of apoptosis: a drop in mitochondrial potential, concurrent with a
      drop in ATP level and a decrease in cell respiration, translocation of
      phosphatidylserine of the plasma membrane, DNA fragmentation, appearance of
      apoptotic bodies and eventually loss of plasma membrane integrity. The chronology
      of these events is in accordance with sequential events induced by other known
      proapoptotic agents; in contrast to these agents that induce apoptosis in a
      restricted part of the cell population, we observed that the entire cell
      population (apart from a small percentage of cells that endured rapid necrosis
      during phototreatment) underwent apoptosis after irradiation in the presence of
      porphyrins. It appears that photodynamic treatment allows the bypass of early
      apoptotic signals in K562 cells that are otherwise renowned for their resistance
      to drug-induced apoptosis (A. McGahon, R. Bissonnette, M. Schmitt, K. M. Cotter,
      D. R. Green and T. G. Cotter, Blood 83, 1179-1187, 1994). Singlet oxygen is
      believed to be the proximate reactive species generated by porphyrin
      illumination. Because this molecule reacts with almost every cellular
      constituent, the way that singlet oxygen or its reactive oxygen species
      byproducts trigger apoptosis remains to be elucidated.

PMID- 10063801
TI  - Protoporphyrin IX fluorescence photobleaching during ALA-mediated photodynamic
      therapy of UVB-induced tumors in hairless mouse skin.
AB  - Fluorescence photobleaching of protoporphyrin IX (PpIX) during superficial
      photodynamic therapy (PDT), using 514 nm excitation, was studied in UVB-induced
      tumor tissue in the SKH-HR1 hairless mouse. The effects of different irradiance
      and light fractionation regimes upon the kinetics of photobleaching and the PDT
      induced damage were examined. Results show that the rate of PpIX photobleaching
      (i.e., fluorescence intensity vs fluence) and the PDT damage both increase with
      decreasing irradiance. We have also detected the formation of fluorescent PpIX
      photoproducts in the tumor during PDT, although the quantity recorded is not
      significantly greater than generated in normal mouse skin, using the same light
      regime. The subsequent photobleaching of the photoproducts also occurs at a rate
      (vs fluence) that increases with decreasing irradiance. In the case of light
      fractionation, the rate of photobleaching increases upon renewed exposure after
      the dark period, and there is a corresponding increase in PDT damage although
      this increase is smaller than that observed with decreasing irradiance. The
      effect of fractionation is greater in UVB-induced tumor tissue than in normal
      tissue and the damage is enhanced when fractionation occurs at earlier time
      points. We observed a variation in the distribution of PDT damage over the
      irradiated area of the tumor: at high irradiance a ring of damage was observed
      around the periphery. The distribution of PDT damage became more homogeneous with
      both lower irradiance and the use of light fractionation. The therapeutic dose
      delivered during PDT, calculated from an analysis of the fluorescence
      photobleaching rate, shows a strong correlation with the damage induced in normal
      skin, with and without fractionation. The same correlation could be made with the
      data obtained from UVB-induced tumor tissue using a single light exposure.
      However, there was no such correlation when fractionation schemes were employed
      upon the tumor tissue.

PMID- 10063802
TI  - Light dose fractionation to enhance photodynamic therapy using 5-aminolevulinic
      acid in the normal rat colon.
AB  - 5-Aminolevulinic acid (ALA) is an attractive photosensitizing agent for
      photodynamic therapy (PDT) as its photoactive derivative, protoporphyrin IX, is
      metabolized within 1-2 days, eliminating prolonged skin photosensitivity.
      However, at the maximum dose patients can tolerate by mouth, 60 mg/kg, only
      superficial effects are seen. This paper extends earlier studies on enhancing the
      effect by light fractionation. Experiments in the normal rat colon looked at the
      area of necrosis around a single light delivery fiber 3 days after PDT with a
      range of light-dose fractionation regimes. All animals were given 200 mg/kg ALA
      intravenously 2 h prior to light delivery (100 mW at 635 nm) and each
      interruption in illumination was for 150 s. The area of PDT necrosis (total dose
      25 J) could be increased by a factor of 3 with a single interval after 5 J,
      compared with continuous illumination. Alternatively, with this single break, the
      total light dose could be reduced by 60% to achieve the same area of necrosis as
      with continuous illumination. This simple modification to PDT with ALA could
      markedly reduce current treatment times as well as increasing clinical efficacy.

PMID- 10063803
TI  - Light activates reduction of methotrexate by NADPH in the ternary complex with
      Escherichia coli dihydrofolate reductase.
AB  - Methotrexate (MTX), a strong inhibitor of dihydrofolate reductase (DHFR), has
      been widely used for chemotherapy for many types of cancer as well as for
      juvenile rheumatoid arthritis. It mimics folate substrates and binds tightly to
      the active site of DHFR, perhaps in a conformation close to the transition state
      of the folate catalyzed reaction. Absorption, fluorescence and ultrasensitive
      Raman difference spectroscopies show that light-activated MTX reacts with NADPH
      in the enzyme active site, producing 5,8-dihydromethotrexate (5,8-dihydro-MTX)
      and NADP+. The reaction, which proceeds with a hydride transfer between C4 (pro-R
      side) of the nicotinamide ring and N5 of the pteridine ring, is similar to that
      between folate and NADPH except that the hydride is transferred to C6 in this
      case. Hence, MTX is catalytically competent in its excited state. Most
      experiments were performed on the Escherichia coli enzyme, but preliminary
      studies show that the reaction also occurs with human DHFR.

PMID- 10063804
TI  - Damage to rat retinal DNA induced in vivo by visible light.
AB  - Intense visible light can damage retinal photoreceptor cells by photochemical or
      thermal processes, leading to cell death. The precise mechanism of light-induced
      damage is unknown; however, oxidative stress is thought to be involved, based on
      the protective effect of antioxidants on the light-exposed retina. To explore the
      in vivo effects of light on retinal DNA, rats were exposed to intense visible
      light for up to 24 h and the time courses of single-strand breaks in restriction
      fragments containing the opsin, insulin 1 and interleukin-6 genes were measured.
      All three gene fragments displayed increasing single-strand modifications with
      increasing light exposure. Treatment with the antioxidant dimethylthiourea prior
      to light exposure delayed the development of net damage. The time course of
      double-strand DNA damage was also examined in specific genes and in repetitive
      DNA. The appearance of discrete 140-200 base-pair DNA fragments after 20 h of
      light exposure implicated a nonrandom, possibly enzymatic damaging mechanism. The
      generation of nucleosome core-sized DNA fragments, in conjunction with single
      strand breaks, suggests two phases of light-induced retinal damage, with random
      attack on DNA by activated oxygen species preceding enzymatic degradation.

PMID- 10063805
TI  - A third member of the photolyase/blue-light photoreceptor family in Drosophila: a
      putative circadian photoreceptor.
AB  - Two photolyases, specific for cyclobutane pyrimidine dimers and (6-4)
      photoproducts, have been reported in Drosophila. These enzymes share extensive
      sequence homologies with the plant blue-light photoreceptor. We have now
      identified a third gene in Drosophila melanogaster with extensive sequence
      homology to the photolyase gene. The newly identified gene, which we named dCRY,
      was expressed as a recombinant protein and tested for photolyase activity. The
      recombinant protein exhibited photochemical properties similar to those of
      Drosophila pyrimidine dimer and (6-4) photolyases but lacked photolyase activity.
      In light of recent evidence that blue-light photoreceptors regulate the circadian
      clock in mammals, we propose that dCRY is the circadian photoreceptor in this
      organism.

PMID- 10063806
TI  - A putative blue-light receptor from Drosophila melanogaster.
AB  - A gene encoding a 62.5 kDa homolog of Drosophila melanogaster photolyase was
      isolated. Purified recombinant protein contained a flavin adenine dinucleotide
      chromophore. The recombinant protein did not show photolyase activity for either
      cyclobutane pyrimidine dimers or 6-4 photoproducts in vitro as well as in vivo in
      Escherichia coli host cells, suggesting that the protein is not a DNA repair
      enzyme but a blue-light photoreceptor. Reverse transcription polymerase chain
      reaction analysis showed that the gene is more expressed in head than in body and
      that it is more expressed in antennae than in legs, wings and mouth appendages.
      In a phylogenetic tree of the photolyase family, the Drosophila photolyase
      homolog is located in a cluster containing 6-4 photolyases and mammalian
      photolyase homologs, which is only distantly related to the clade of higher plant
      blue-light photoreceptors. The mammalian photolyase homologs are more closely
      related to Drosophila 6-4 photolyase than to the Drosophila photolyase homolog,
      suggesting different roles of the photolyase homologs.

PMID- 10063807
TI  - Abscess related to anabolic-androgenic steroid injection.
AB  - One million individuals in the United States, predominantly males under 25 yr of
      age, are current or past users of anabolic-androgenic steroids. Fifty percent of
      these young adults administer their drugs intramuscularly, placing them at risk
      for infections related to injection. We present here a case report of an
      injection-related thigh abscess in a 26-yr-old anabolic steroid injector who did
      not use sterile injection technique and reported sharing multidosage vials with
      two other weightlifting colleagues. Reported infections associated with anabolic
      androgenic steroid injection include abscesses attributable to Mycobacterium
      smegmatis, Staphylococcus, Streptococcus, and Pseudomonas organisms as well as
      HIV, hepatitis B, and hepatitis C. These infections are primarily related to
      nonsterile injection technique, shared injection equipment, and are avoidable
      with appropriate prevention techniques. Education is needed to prevent infectious
      complications such as abscesses and blood-borne pathogens among anabolic
      androgenic steroid injectors.

PMID- 10063808
TI  - Laxity, instability, and functional outcome after ACL injury: copers versus
      noncopers.
AB  - PURPOSE: The purpose of this study was to determine the relationship among
      laxity, quadriceps strength, instability, and function in subjects with complete
      rupture of the anterior cruciate ligament (ACL) who compensate well for the
      injury (copers) and those who require surgical stabilization (noncopers).
      METHODS: Forty-five patients with unilateral ACL rupture (confirmed via
      arthroscopy or magnetic resonance imaging (MRI) and arthrometer measurements)
      participated in this study. Subjects were divided into two groups: copers (N =
      12), and subacute noncopers (N = 18) and chronic noncopers (N = 15). All copers
      had returned to all preinjury activity (including index sport) without
      limitation. Maximum manual anterior tibiofemoral laxity measurements, quadriceps
      femoris muscle strength measurements, and a series of hop tests were performed.
      Lysholm Scale, Knee Outcome Survey (KOS), global rating of knee function, and the
      International Knee Documentation Committee (IKDC) form were completed. RESULTS:
      There was no significant difference in laxity between copers (X = 5.5+/-2.7 mm)
      and noncopers (chronic, X = 5.1+/-2.8 mm and subacute, X = 4.2+/-2.2 mm) or in
      IKDC scores among the groups. The copers, however, scored significantly better
      than the chronic and subacute ACL-deficient subsets on all other measures.
      Measurements of laxity were not correlated to any functional outcome measure or
      to episodes of instability. CONCLUSIONS: Copers were not different in any
      meaningful way from the noncopers before injury, had equal or greater side-to
      side laxity differences, and functioned normally. A battery of tests was
      identified that accurately discriminated noncopers from copers even early after
      injury. Thus, measurements of laxity alone are insufficient for determining
      functional status after ACL injury.

PMID- 10063809
TI  - Quality of life and anxiety in a phase II cardiac rehabilitation program.
AB  - PURPOSE: Cardiac rehabilitation programs increasingly attempt to improve both
      quantity and quality of life (QOL). Documenting QOL changes requires appropriate
      instruments, and interpreting QOL data requires an understanding of the factors
      that influence such reports. METHODS: To address both issues, we assessed QOL
      among 77 patients before and after participation in a 12-wk phase II cardiac
      rehabilitation program. Individual psychological differences in trait anxiety and
      defensiveness were also assessed. The sample was 76.6% male, 70.1% married, and
      had a mean age of 58.8 yr. RESULTS: The QOL scales detected changes which
      occurred over the 12-wk testing period. QOL reports were strongly and
      differentially influenced by individual differences in trait anxiety, such that
      patients reporting high trait anxiety displayed poorer QOL than those low in
      trait anxiety. More specifically, trait anxiety influenced affect reports most
      strongly, functional aspects moderately, and physical aspects of QOL reports the
      least. CONCLUSIONS: Defensiveness was unrelated to QOL reports. The 17% of
      participants who voluntarily left the rehabilitation program prematurely were
      characterized as younger, having better self-perceived health, having a less
      severe cardiac history, and being high in both trait anxiety and defensiveness.
      Study benefits and limitations are discussed.

PMID- 10063810
TI  - Exertional heat stroke: a case series.
AB  - Exertional heat stroke (EHS) is a state of extreme hyperthermia that occurs when
      excess heat that is generated by muscular exercise exceeds the body's ability to
      dissipate it at the same rate. EHS is thought to coincide with previously
      healthy, highly motivated, and relatively untrained individuals exerting in hot
      environments for long periods. PURPOSE: To establish this notion, the present
      study was aimed to follow the trends in the incidence of EHS in the period 1988
      1996. METHODS: During these years, 150 cases of male soldiers (age = 20+/-3 yr)
      were reported to our institute as suffering from heat illnesses. According to the
      files, 82 cases were definitely diagnosed as EHS. RESULTS: More than 50% of the
      cases occurred during the first 6 months in service. Most of the cases occurred
      during the summer season (June-September), but 30% of the cases occurred during
      the spring. EHS was not related to time in the day. Many cases occurred during
      the night or early morning, even under mild heat load. Forty percent of the cases
      occurred during very short activities, and about 60% occurred already during the
      first 2 h of exercise. The results were discussed in view of the regulations
      which prevail in the Israeli army. CONCLUSIONS: It seems that almost all EHS
      cases occurred when regulations were not strictly followed.

PMID- 10063811
TI  - Weight and diet concerns in Finnish female and male athletes.
AB  - PURPOSES AND METHODS: Factors related to eating disorders were studied in five
      groups of female (N = 173) and male (N = 190) athletes, and in female (N = 79)
      and male (N = 61) controls. Factors associated with menstrual status were also
      examined. RESULTS: The sum of drive for thinness and body dissatisfaction
      subscales in the Eating Disorders Inventory was higher (P < 0.05) in female
      controls (median: 5; 25th and 75th percentiles: 1 and 14) than in endurance
      athletes (0; 0 and 2). The male groups did not differ from each other (P = 0.08)
      or from female subjects (P = 0.62). The preferred weight loss in the female
      controls (-4.0 kg; -6.2 and -2.0) was larger (P < 0.05) than in most athletic
      groups. Males, on average, did not want to lose weight (different from females, P
      < 0.001). The prevalence of weight reduction attempts (85%) in female weight
      class athletes was higher (P < 0.05) compared with endurance and ballgame
      athletes and the controls (29-58%). In males, the frequency (93%) of weight
      reduction attempts was also highest in the weight-class athletes (P < 0.05). The
      prevalence of menstrual disturbances was 27-37% in aesthetic, endurance, and
      weight-class athletes, and 5% in controls (P = 0.06). CONCLUSIONS: The results
      confirmed that the risk for eating disorders is dependent on the type of sport.
      The claim that some female athlete groups are at greater risk than controls did
      not receive evidence.

PMID- 10063812
TI  - Phosphocreatine resynthesis is not affected by creatine loading.
AB  - PURPOSE: Oral creatine supplementation has been shown to improve power output
      during high intensity intermittent muscle contractions. Facilitated muscle
      phosphocreatine (PCr) resynthesis, by virtue of elevated intracellular PCr
      concentration, might contribute to this ergogenic action. Therefore, the effect
      of creatine loading (C: 25 g X d(-1) for 5 d) on muscle PCr breakdown and
      resynthesis and muscle performance during high intensity intermittent muscle
      contractions was investigated. METHODS: A double-blind randomized cross-over
      study was performed in young healthy male volunteers (N = 9). 31P-NMR
      spectroscopy of the m. gastrocnemius and isokinetic dynamometry of knee-extension
      torque were performed before and after 2 and 5 d of either placebo (P) or C
      administration. RESULTS: Compared with P, 2 and 5 d of C increased (P < 0.05)
      resting muscle PCr concentration by 11% and 16%, respectively. Furthermore,
      torque production during maximal intermittent knee extensions, including the
      first bout of contractions, was increased (P < 0.05) by 5-13% by either 2 or 5 d
      of C. However, compared with P, the rate of PCr breakdown and resynthesis during
      intermittent isometric contractions of the calf was not significantly affected by
      C. CONCLUSION: Creatine loading raises muscle PCr concentration and improves
      performance during rapid and dynamic intermittent muscle contractions. Creatine
      loading does not facilitate muscle PCr resynthesis during intermittent isometric
      muscle contractions.

PMID- 10063813
TI  - Rat liver lysosomal and mitochondrial activities are modified by anabolic
      androgenic steroids.
AB  - PURPOSE: The aim of this study was to examine the separate and combined effects
      of an 8-wk treatment with high doses of 17alpha-alkylated anabolic-androgenic
      steroids (AAS) and exercise training on selected lysosomal and mitochondrial
      enzyme activities in rat liver. METHODS: Sedentary and treadmill-trained (25 m x
      min(-1), 45 min x d(-1), 5 d x wk(-1)) male rats were treated with
      fluoxymesterone, methylandrostanolone, or stanozolol (2 mg x kg body weight(-1),
      5 d x wk(-1)) for 8 wk. RESULTS: Acid phosphatase, arylsulfatase, beta
      glucuronidase, and beta-galactosidase activities were increased in liver
      homogenates of sedentary and trained AAS-treated rats. The mitochondrial
      respiratory chain activities rotenone-sensitive NADH-cytochrome c reductase
      (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome oxidase (COX)
      showed a significant decrease in steroid-administered rats, whereas citrate
      synthase (CS), a matrix enzyme, exhibited no changes in activity, pointing to a
      selective effect of AAS on mitochondrial membrane complexes. In vitro studies in
      mitochondrial fractions isolated from the liver of control rats showed that COX
      and CS activities were insensitive to the AAS, whereas NCCR and SCCR activities
      were partly inhibited. On the other hand, the mean values of serum parameters
      related to hepatic function were within normal ranges in all the experimental
      groups of animals. CONCLUSIONS: The present data show that 8-wk ingestion of
      three different anabolic-androgenic steroids, either with or without concurrent
      exercise training, affects lysosomal hydrolases and mitochondrial respiratory
      chain electron transport in rat liver without modifying classical serum
      indicators of hepatic function.

PMID- 10063814
TI  - Effects of precooling on thermoregulation during subsequent exercise.
AB  - PURPOSE: The purpose of this study was to examine the effect of a decreased body
      core temperature before a simulated portion of a triathlon (swim,15 min; bike, 45
      min) and examine whether precooling could attenuate thermal strain and increase
      subjective exercise tolerance in a warm environment (26.6 degrees C/60% relative
      humidity (rh)). METHODS: Six endurance trained triathletes (28+/-2 yr, 8.2+/-1.7%
      body fat) completed two randomly assigned trials 1 wk apart. The precooling trial
      (PC) involved lowering body core temperature (-0.5 degrees C rectal temperature,
      Tre) in water before swimming. The control trial (CON) was identical except no
      precooling was performed. Water temperature and environmental conditions were
      maintained at 25.6 degrees C and 26.6 degrees C/60% rh, respectively, throughout
      all testing. RESULTS: Mean time to precool was 31+/-8 min and average time to
      reach baseline Tre during cycling was 9+/-7 min. Oxygen uptake (VO2), HR, skin
      temperature (Tsk), Tre, RPE, and thermal sensation (TS) were recorded following
      the swim segment and throughout cycling. No significant differences in mean body
      (Tb) or Tsk were noted between PC and CON, but a significant difference (P <
      0.05) in Tre between treatments was noted through the early phases of cycling. No
      significant differences were reported in HR, VO2, RPE, TS, or sweat rate (SR)
      between treatments. Body heat storage (S) was negative following swimming in both
      PC (-92+/-6 W x m2) and CON (-66+/-9 W x m2). A greater S occurred in PC (109+/-6
      W x m2) vs CON (79+/-4 W x m2) during cycling (P < 0.05). CONCLUSIONS: Precooling
      attenuated the rise in Tre, but this effect was transient. Therefore, precooling
      is not recommended before a triathlon under similar environmental conditions.

PMID- 10063815
TI  - Systolic and diastolic cardiac function time intervals and exercise capacity in
      women.
AB  - PURPOSE: To determine the relationship between exercise capacity and resting
      cardiac function time intervals in women. METHODS: The noninvasive method of
      seismocardiography was used to measure resting cardiac intervals in 12 female
      subjects. On the basis of maximal treadmill time (Bruce protocol), two groups
      were studied and categorized as long duration runners (LDR; N = 6) or short
      duration runners (SDR, N = 6). The following resting atrial and left ventricular
      (LV) cardiac function time intervals were determined: atrial systole, LV systole,
      LV diastole, LV isovolumetric contraction, LV isovolumetric relaxation, LV
      ejection, LV preejection, LV filling, LV rapid filling, and Tei index. RESULTS:
      Heart rate (HR) (65+/-3 vs 61+/-4 b x min(-1) for LDR and SDR, respectively; P =
      NS) and atrial systolic time (75+/-6 vs 81+/-5 ms for LDR and SDR, respectively;
      P = NS) were similar between groups. LV systole (348+/-15 vs 302+/-8 ms for LDR
      and SDR, respectively; P < 0.05) and LV ejection (297+/-13 vs 247+/-7 ms for LDR
      and SDR, respectively; P < 0.01) were longer in LDR, despite a similar LV
      isovolumetric contraction time. There was a general trend for a shortened LV
      diastole in LDR with a significantly shortened LV isovolumetric time in LDR (80+/
      8 vs 107+/-8 ms for LDR and SDR, respectively; P < 0.05). LV preejection was
      shorter in LDR versus SDR (LDR; 114+/-6 vs SDR; 130+/-3 ms, P < 0.05), and the
      Tei index was less in LDR versus SDR. CONCLUSIONS: Independent of HR, increased
      treadmill time in young women is associated with greater resting systolic time
      intervals and decreased diastolic cardiac function time intervals.

PMID- 10063816
TI  - Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic
      capacity.
AB  - PURPOSE: The purpose of the study was to examine the effect of a very short
      intermittent exposure to moderate hypoxia in a hypobaric chamber on aerobic
      performance capacity at sea level and the erythropoietic response. The effects of
      hypobaric hypoxia alone and combined with low-intensity exercise were also
      compared. METHODS: Seventeen members of three high-altitude expeditions were
      exposed to intermittent hypoxia in a hypobaric chamber over 9 d at simulated
      altitude, which was progressively increased from 4000 to 5500 m in sessions
      ranging from 3 to 5 h x d(-1). One group (N = 7; HE group) combined passive
      exposure to hypoxia with low-intensity exercise on a cycle ergometer. Another
      group (N = 10; H group) was only exposed to passive hypoxia. Before and after the
      exposure to hypoxia, medical status, performance capacity, and complete
      hematological and hemorheological profile of subjects were evaluated. RESULTS: No
      significant differences were observed between the two groups (HE vs H) in any of
      the parameters studied, indicating that hypoxia alone was responsible for the
      changes. After the acclimation period, a significant increase in exercise time
      (mean difference: +3.9%; P < 0.01), and maximal pulmonary ventilation (+5.5%; P <
      0.05) was observed during the maximal incremental test at sea level. Individual
      lactate-velocity curves significantly shifted to the right (P < 0.05), thus
      revealing an improvement of aerobic endurance. A significant increase was found
      in PCV (42.1-45.1%; P < 0.0001), RBC count (5.16 to 5.79 x 10(6) x mm(-3); P <
      0.0001), reticulocytes (0.5 to 1.1%; P < 0.0001) and hemoglobin (Hb)
      concentration (14.2 to 16.7 g x dL(-1); P < 0.002). CONCLUSIONS: It was concluded
      that short-term hypobaric hypoxia can activate the erythropoietic response and
      improve the aerobic performance capacity in healthy subjects.

PMID- 10063817
TI  - The role of the right ventricle during hypobaric hypoxic exercise: insights from
      patients after the Fontan operation.
AB  - OBJECTIVES: The principal objective of this study was to examine the importance
      of the right ventricle for maximal systemic oxygen transport during exercise at
      high altitude by studying patients after the Fontan operation. BACKGROUND: High
      altitude-induced hypoxia causes a reduction in maximal oxygen uptake. Normal
      right ventricular pump function may be critical to sustain cardiac output in the
      face of hypoxic pulmonary vasoconstriction. We hypothesized that patients after
      the Fontan operation, who lack a functional subpulmonary ventricle, would have a
      limited exercise capacity at altitude, with an inability to increase cardiac
      output. METHODS: We measured oxygen uptake (VO2, Douglas bag), cardiac output
      (Qc, C2H2 rebreathing), heart rate (HR) (ECG), blood pressure (BP) (cuff), and O2
      Sat (pulse oximetry) in 11 patients aged 14.5+/-5.2 yr (mean +/- SD) at 4.7+/-1.6
      yr after surgery. Data were obtained at rest, at three submaximal steady state
      workrates, and at peak exercise on a cycle ergometer. All tests were performed at
      sea level (SL) and at simulated altitude (ALT) of 3048 m (10,000 ft, 522 torr) in
      a hypobaric chamber. RESULTS: At SL, resting O2 sat was 92.6+/-4%. At ALT, O2 sat
      decreased to 88.2+/-4.6% (P < 0.05) at rest and decreased further to 80+/-6.3% (P
      < 0.05) with peak exercise. At SL, VO2 increased from 5.1+/-0.9 mL x kg(-1) x
      min(-1) at rest to 23.5+/-5.3 mL x kg(-1) x min(-1) at peak exercise and CI (Qc x
      m(-2)) increased from 3.3+/-0.7 L x m(-2) to 6.2+/-1.2 L x m(-2). VO2 peak,
      17.8+/-4 mL x kg(-1) x min(-1) (P < 0.05), and CI peak, 5.0+/-1.5 L x m(-2) (P <
      0.05), were both decreased at ALT. Remarkably, the relationship between Qc and
      VO2 was normal during submaximal exercise at both SL and ALT. However at ALT,
      stroke volume index (SVI, SV x m(-2)) decreased from 37.7+/-8.6 mL x min(-1) x m2
      at rest, to 31.3+/-8.6 mL x min(-1) x m2 at peak exercise (P < 0.05), whereas it
      did not fall during sea level exercise. CONCLUSIONS: During submaximal exercise
      at altitude, right ventricular contractile function is not necessary to increase
      cardiac output appropriately for oxygen uptake. However, normal right ventricular
      pump function may be necessary to achieve maximal cardiac output during exercise
      with acute high altitude exposure.

PMID- 10063818
TI  - Ventilatory responses to dynamic exercise elicited by intramuscular sensors.
AB  - PURPOSE: Eight subjects, aged 27.0+/-1.6 yr, performed incremental workload
      cycling to investigate the contribution of skeletal muscle mechano- and
      metaboreceptors to ventilatory control during dynamic exercise. METHODS: Each
      subject performed four bouts of exercise: exercise with no intervention (CON);
      exercise with bilateral thigh cuffs inflated to 90 mm Hg (CUFF); exercise with
      application of lower-body positive pressure (LBPP) to 45 torr (PP); and exercise
      with 90 mm Hg thigh cuff inflation and 45 torr LBPP (CUFF+PP). Ventilatory
      responses and pulmonary gas exchange variables were collected breath-by-breath
      with concomitant measurement of leg intramuscular pressure. RESULTS: Ventilation
      (VE) was significantly elevated from CON during PP and CUFF+PP at workloads
      corresponding to > or = 60% CON peak oxygen uptake (VO2peak) and during CUFF at
      workloads > or = 80% CON VO2peak, P < 0.05. The VO2 at which ventilatory
      threshold occurred was significantly reduced from CON (2.17+/-0.28 L x min(-1))
      to 1.60+/-0.19 L x min(-1), 1.45+/-0.15 L x min(-1), and 1.15+/-0.11 L x min(-1)
      during CUFF, PP, and CUFF+PP, respectively. The slope of the linear regression
      describing the VE/CO2 output relationship was increased from CON by approximately
      22% during CUFF, 40% during PP, and 41% during CUFF+PP. CONCLUSIONS: As
      intramuscular pressure was significantly elevated immediately upon application of
      LBPP during PP and CUFF+PP without a concomitant increase in VE, it seems
      unlikely that LBPP-induced increases in VE can be attributed to activation of the
      mechanoreflex. These findings suggest that LBPP-induced reductions in perfusion
      pressure and decreases in venous outflow resulting from inflation of bilateral
      thigh cuffs may generate a metabolite sensitive intramuscular ventilatory
      stimulus.

PMID- 10063819
TI  - Physical fitness and clustering of risk factors associated with the metabolic
      syndrome.
AB  - PURPOSE: The purposes of this study were to 1) assess the prevalence of
      clustering of metabolic markers of the MS in a defined population and 2)
      determine the association between CRF and such clustering in a large group of
      adult men (N = 15,537) and women (N = 3,899). METHODS: Metabolic markers of the
      MS included systolic blood pressure (BP) > or = 140 mm Hg, serum triglycerides >
      or = 150 mg x dL(-1), fasting blood glucose > or = 110 mg x dL(-1), and elevated
      central adiposity (waist circumference > 100 cm). Cardiorespiratory fitness was
      defined as total time on a maximal treadmill exercise test. The cohort was
      grouped by the number of metabolic abnormalities and level of CRF. Associations
      between CRF and the number of metabolic abnormalities were assessed using
      proportional odds logit models. RESULTS: Among men, the age-adjusted cumulative
      odds ratio for abnormal markers of the MS was 3.0 (95% C.I. 2.7-3.4; P < 0.001)
      for the least-fit men when compared with moderately-fit ones, and 10.1 (95% C.I.
      9.1-11.2; P < 0.001) when compared with the most-fit men. Among women, the age
      adjusted cumulative odds ratio was 2.7 (95% C.I. 2.1-3.5; P < 0.001) for the
      least-fit women when compared with moderately-fit ones, and 4.9 (95% C.I. 3.8
      6.3; P < 0.001) when compared with the most-fit women. CONCLUSIONS: These cross
      sectional results suggest that low CRF is associated with an increased clustering
      of the metabolic abnormalities associated with the MS in both adult men and women
      and support the need for future prospective analyses.

PMID- 10063820
TI  - Muscle coordination and function during cutting movements.
AB  - PURPOSE: The objectives of this study were to: 1) establish a database of
      kinematic and EMG data during cutting movements, 2) describe normal muscle
      function and coordination of 12 lower extremity muscles during cutting movements
      susceptible to ankle sprains, and 3) identify potential muscle coordination
      deficiencies that may lead to ankle sprain injuries. METHODS: Kinematic, EMG, and
      GRF data were collected from 10 recreationally active male subjects during both a
      side-shuffle and v-cut movement. RESULTS: The data showed that muscles functioned
      similarly during both movements. The primary function of the hip and knee
      extensors was to decelerate the center-of-mass during landing and to provide
      propulsion during toe-off. The hip add/abductors functioned primarily to
      stabilize the hip rather than provide mechanical power. The ankle plantar flexors
      functioned to provide propulsion during toe-off, and the gastrocnemius had an
      additional burst of activity to plantarflex the foot before touchdown during the
      side-shuffle to help absorb the impact. The tibialis anterior functioned
      differently during each movement: to dorsiflex and supinate the foot after toe
      off in preparation for the next step cycle during the side-shuffle and to
      dorsiflex the foot before impact to provide the heel-down landing and ankle
      stability in the stance phase during the v-cut. CONCLUSIONS: The muscles crossing
      the ankle joint, especially the tibialis anterior and peroneus longus, may play
      an important role to prevent ankle sprain injuries. Both muscles provided
      stability about the subtalar joint by preventing excessive joint rotations.
      Future theoretical studies with forward dynamic simulations incorporating
      individual muscle actuators are needed to quantify the segment accelerations
      induced by active muscles which may prevent or lead to ankle sprain injuries.

PMID- 10063821
TI  - Dynamics of force and muscle stimulation in human vertical jumping.
AB  - PURPOSE: The purpose of this study was to gain insight into the importance of
      stimulation dynamics for force development in human vertical jumping. METHODS:
      Maximum height squat jumps were performed by 21 male subjects. As a measure of
      signal dynamics, rise time (RT) was used, i.e., the time taken by the signal to
      increase from 10% to 90% of its peak value. RT were calculated for time histories
      of smoothed rectified electromyograms (SREMG) of seven lower extremity muscles,
      net moments about hip, knee, and ankle joints, and components of the ground
      reaction force vector. RESULTS: Average RT values were 105-143 ms for SREMG
      signals, 90-112 ms for joint moments, and 120 ms for the vertical component of
      the ground reaction force (Fz). A coefficient of linear correlation of 0.88 was
      found between RT of SREMG of m. gluteus maximus (GLU) and RT of Fz. To explain
      this correlation, it was speculated that for an effective transfer from joint
      extensions to vertical motion of the center of mass (CM), the motion of CM needs
      a forward component during the push-off. Given the starting position, only the
      hip extensor muscles are able to generate such a forward acceleration of CM. To
      preserve the forward motion of CM, RT of knee and ankle joint moments need to be
      adjusted to RT of the hip joint moment. Thus, the greater RT of the hip joint
      moment and RT of GLU-SREMG, the greater RT of Fz. CONCLUSIONS: Overall, it was
      concluded that the time it takes to develop muscle stimulation has a substantial
      effect on the dynamics of force development in vertical jumping, and that this
      effect should not be neglected in studies of the control of explosive movements.

PMID- 10063822
TI  - The energy cost of horizontal walking and running in adolescents.
AB  - PURPOSE: This study developed and cross-validated generalized equations for
      predicting VO2 (mL x kg(-1) x min(-1)) and caloric expenditure (kcal x kg(-1) x
      min(-1)) during horizontal walking and running in adolescents. METHODS: Subjects
      were 47 male and 35 female adolescent volunteers, ages 12-18. Each subject
      underwent a submaximal treadmill exercise test to determine VO2 at randomly
      selected walking and jogging speeds (67-215 m x min(-1)). Caloric expenditure was
      estimated from VO2 and RER. Multiple regression was used to develop prediction
      equations for estimating VO2 and caloric expenditure from a derivation sample of
      77 random observations, both walking and running. RESULTS: The group relationship
      between running speed and energy cost in the derivation sample was linear,
      whereas the relationship between walking speed and energy cost was quadratic.
      Gender, age, and height each failed to account for significant additional
      variation in energy cost after speed and mode were considered. Skinfolds
      accounted for a small yet significant amount of additional variation in energy
      cost. The derived equations were cross-validated on a sample of 76 separate
      random observations. The cross-validation statistics are: for VO2, R = 0.95,
      error = 3.58 mL x kg(-1) x min(-1), and for caloric expenditure, R = 0.94, error
      = 0.019 kcal x kg(-1) x min(-1). Most selected adult equations consistently
      underestimated both VO2 and caloric expenditure in the cross-validation sample.
      CONCLUSIONS: These results suggest that in adolescents, within the range of
      speeds tested, the relationship between speed of movement and energy cost for
      running is linear, but for walking is curvilinear. Also, adult models for
      estimating VO2 or caloric expenditure do not account for the higher relative
      energy cost of walking and running in adolescents.

PMID- 10063823
TI  - Effects of ballistic training on preseason preparation of elite volleyball
      players.
AB  - PURPOSE: The purpose of this study was to determine whether ballistic resistance
      training would increase the vertical jump (VJ) performance of already highly
      trained jump athletes. METHODS: Sixteen male volleyball players from a NCAA
      Division I team participated in the study. A Vertec was used to measure standing
      vertical jump and reach (SJR) and jump and reach from a three-step approach
      (AJR). Several types of vertical jump tests were also performed on a Plyometric
      Power System and a forceplate to measure force, velocity, and power production
      during vertical jumping. The subjects completed the tests and were then randomly
      divided into two groups, control and treatment. All subjects completed the usual
      preseason volleyball on-court training combined with a resistance training
      program. In addition, the treatment group completed 8 wk of squat jump training
      while the control group completed squat and leg press exercises at a 6RM load.
      Both groups were retested at the completion of the training period. RESULTS: The
      treatment group produced a significant increase in both SJR and AJR of 5.9+/-3.1%
      and 6.3+/-5.1%. respectively. These increases were significantly greater than the
      pre- to postchanges produced by the control group, which were not significant for
      either jump. Analysis of the data from the various other jump tests suggested
      increased overall force output during jumping, and in particular increased rate
      of force development were the main contributors to the increased jump height.
      CONCLUSIONS: These results lend support to the effectiveness of ballistic
      resistance training for improving vertical jump performance in elite jump
      athletes.

PMID- 10063824
TI  - Physical work capacity after 7 wk of wheelchair training: effect of intensity in
      able-bodied subjects.
AB  - PURPOSE: The purpose of this study was to study the effects of a 7-wk wheelchair
      training program on physical work capacity in able-bodied subjects. Effects of
      training intensities of 50 and 70% heart rate (HR) reserve (HRR) were studied for
      different subject groups. METHODS: Twenty-seven able-bodied male subjects
      participated in this study. They were randomly divided into a control group (N =
      8), a 50%-intensity group (N = 9), and a 70%-intensity group (N = 10). The 50%-
      and the 70%-intensity groups received a 7-wk wheelchair training program: three
      times a week, one-half hour wheelchair exercise on a motor driven treadmill at an
      average intensity of 50 and 70% of the HRR, respectively. Before and after the
      training period, parameters for physical work capacity (maximal isometric
      strength (Fiso), sprint power (P30), maximal power output (POmax) and peak oxygen
      uptake (VO2peak)), and submaximal performance (mechanical efficiency, HR) at 20
      and 40% of the estimated POmax (ME20, ME40; HR20, HR40) were obtained during
      tests on a stationary wheelchair ergometer. RESULTS: A two-factor ANOVA for
      repeated measures on the within-subjects factor "pre-post tests," the between
      subject factor training (50% and 70% training vs control) and the interaction
      term showed that the 50%-intensity group significantly increased on P30 and POmax
      compared with the control group. The 70% intensity group significantly increased
      on P30, POmax and VO2peak compared with the control group (P < 0.05). The 70%
      group did not show significantly higher increases in P30 and POmax over training
      than the 50% intensity. No significant effects were found for the Fiso and the
      parameters at submaximal PO. CONCLUSIONS: The wheelchair training at both
      intensities can have favorable effects on maximal physical work capacity in able
      bodied subjects, and possibly also on mechanical efficiency at submaximal power
      output. Effects are seen in parameters for both aerobic and anaerobic work
      capacities. Although training at 70% intensity was more effective than the 50%
      intensity, training at 50% HRR may initially be more appropriate in untrained
      individuals, such as novice wheelchair users at the start of their
      rehabilitation, to prevent fatigue and enhance motivation.

PMID- 10063825
TI  - Oxygen uptake, heart rate, and blood lactate responses during and following
      karate training.
AB  - PURPOSE: The purpose of this study was to examine whether each exercise and an
      entire karate training session can achieve: 1) accepted training intensity
      thresholds for effective aerobic capacity training, 2) energy expenditure (EE)
      thresholds for total body mass and fat weight loss, and 3) elevation in excess
      postexercise oxygen consumption (EPOC). METHODS: We investigated physiological
      responses during five types of karate training: basic techniques without (S
      Basics) and with (M-Basics) movements, sparring techniques without (TECH I) and
      with (TECH II) an opponent, and kata. RESULTS: The mean percent of maximal oxygen
      uptake (%VO2max) and HR (%HRmax) for S-Basics were below the accepted threshold
      (60% of HRmax or 50% of VO2max) and for M-Basics, TECH I and TECH II were above
      the threshold for increasing VO2max. For kata and the entire 70 min of karate
      training, the mean %HRmax were slightly above the threshold, and %VO2max were
      slightly below the threshold. The mean EPOC measured for 5 min immediately
      following 70 min of karate training did not differ from the resting VO2. The mean
      EE resulting from 70 min of karate exercise and EPOC were 2355.4+/-316.3 kJ and
      38.8+/-32.7 kJ, respectively. CONCLUSIONS: Although the training intensity of
      karate exercises studied was moderate and the effects of karate training on EPOC
      were minimal, the mean value of EE was well above the accepted threshold for
      total body mass and fat weight loss.

PMID- 10063826
TI  - Utility of pwc75% as an estimate of aerobic power in epidemiological and
      population-based studies.
AB  - PURPOSE: Studies of physical activity often assess physical work capacity (pwc)
      and this is usually achieved with extrapolated estimates of maximal aerobic power
      (VO2max). However, extrapolation beyond the measured values may be problematic,
      particularly for older subjects. On a population basis, interpolated measures of
      pwc may provide the same information and avoid the errors associated with
      extrapolated measures. METHODS: This study assessed extrapolated (pwc at 150 and
      170 beats x min(-1) heart rate (HR) and estimated VO2max) and interpolated (pwc
      at 75% of maximum HR: pwc75%) measures of pwc in a population sample of 1043 men
      and women aged 18-78 yr. Each measure was assessed to determine whether it showed
      the key characteristics of measured VO2max: a decrease with age and an increase
      with reported physical activity. RESULTS: Both pwc150 and pwc170 did not decline
      with age, estimated VO2max (est.VO2max) exhibited a spurious plateau for older
      age groups, while pwc75% declined approximately 9% per decade of age. All four
      pwc measures detected a significant difference (approximately 10-15%) between
      inactive and active groups classified according to a questionnaire of leisure
      time physical activity. CONCLUSIONS: Although the pwc75% test requires direct
      validation, these results suggest that it may be a useful submaximal exercise
      measure for epidemiological studies of aerobic power.

PMID- 10063827
TI  - Clinical nomenclature for tendon injuries.

PMID- 10063828
TI  - ACSM/AHA joint position statement. American College of Sports Medicine. American
      Heart Association.

PMID- 10063829
TI  - Exclusion of muscle specific actinin-associated LIM protein (ALP) gene from 4q35
      facioscapulohumeral muscular dystrophy (FSHD) candidate genes.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder
      for which no candidate gene has yet been identified. The gene corresponding to
      one of the novel human cDNAs that we cloned on the basis of a muscle restricted
      expression pattern [Pietu G, Alibert O, Guichard B, et al. Genome Res 1996;6:492
      503] was mapped in the region of the FSHD1A genetic locus, i.e. one of the loci
      involved in this muscular dystrophy. The corresponding encoded protein contains a
      PDZ and a LIM domain, two protein-protein interaction domains, and was very
      recently shown to bind alpha-actinin-2 and was named ALP (actinin-associated LIM
      protein) [Xia H, Winokur S, Kuo W, Altherr M, Bredt D. J Cell Biol 1997;139:507
      515]. We raised a specific polyclonal anti-ALP serum against an ALP recombinant
      polypeptide to evaluate the size, level of expression and subcellular
      localization of ALP in three patients, clearly diagnosed with FSHD disease.
      Quantitative or qualitative alterations of ALP expression have not been detected
      in any of them, thus prompting us to exclude ALP as a FSHD gene candidate.

PMID- 10063830
TI  - Higher content of insulin-like growth factor-I in dystrophic mdx mouse: potential
      role in the spontaneous regeneration through an electrophysiological
      investigation of muscle function.
AB  - Insulin-like growth factor-I (IGF-I) is known to promote proliferation and
      differentiation of muscle cells during growth and regeneration. Both these
      conditions are characterized by acquisition of specialized muscle functions, such
      as a large macroscopic chloride conductance (GCl), a parameter that is a target
      of growth hormone (GH)/IGF-I axis action on skeletal muscle. The present study
      has been aimed at evaluating the role of IGF-I in the spontaneous regeneration
      occurring in hind limb muscle of dystrophic mdx mouse. IGF-I levels have been
      measured in hind limb muscles, plasma and liver of mdx and control mice of 8-10
      weeks and 5 months of age by radioimmunoassay. In parallel the biophysical and
      pharmacological properties of muscle chloride channels of extensor digitorum
      longus (EDL) muscle fibers of mice belonging to the same age-group have been
      measured electrophysiologically in vitro. At 8-10 weeks of age, significantly
      greater amounts of IGF-I were found in plasma and hind limb muscles of mdx mice
      with respect to controls. Such a difference was only just detectable and no
      longer statistically significant at 5 months of age. No differences were found in
      hepatic IGF-I levels at either age. The EDL muscle fibers of mdx mice at 8-10
      weeks of age were characterized by higher GCl values and by a different
      pharmacological sensitivity to the enantiomers of 2-(p-chlorophenoxy)-propionic
      acid (CPP), specific chloride channel ligands, with respect to age-matched
      controls. However, these differences were no longer detected at 5 months of age.
      Our results suggest a role of IGF-I in the high regenerative potential of muscles
      from mdx mice and support the hypothesis that the biophysical and pharmacological
      properties of chloride channels of EDL muscle fibers are sensitive indices of the
      action of regeneration-promoting factors on muscle function.

PMID- 10063831
TI  - Clinical and genetic characteristics of a five-generation family with a novel
      form of myotonic dystrophy (DM2).
AB  - We report the clinical and genetic characteristics of a five-generation family
      (MN1) with an unusual form of myotonic dystrophy (DM). Affected individuals have
      clinical features that are similar to DM including myotonia, distal weakness,
      frontal balding, polychromatic cataracts, infertility and cardiac arrhythmias.
      Genetic analyses reveal that affected individuals do not have the CTG expansion
      associated with DM, nor is the disease locus linked to the DM region of
      chromosome 19. We have also excluded the MN1 disease locus from the chromosomal
      regions containing the genes for the muscle sodium (alpha- and beta-subunits) and
      chloride channels, both of which are involved in other myotonic disorders. We
      have recently mapped the disease locus (DM2) in this family to a 10 cM region of
      chromosome 3q [Ranum LPW, Rasmussen PF, Benzow KA, Koob MD, Day JW. Nat Genet
      1998;19:196-198]. The genetically distinct form of myotonic dystrophy in the MN1
      kindred shares some of the clinical features of previously reported families with
      proximal myotonic myopathy (PROMM). The size of the MN1 family (25 affected
      individuals) makes it a unique resource for both clinical and genetic studies.
      This second form of myotonic dystrophy may help resolve the confusion that
      remains about how the CTG repeat expansion in the 3' untranslated portion of the
      myotonin protein kinase gene causes the multisystem involvement of DM.

PMID- 10063832
TI  - Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies.
AB  - We evaluated transforming growth factor-beta1 (TGF-beta1) expression in the
      muscle of four laminin alpha2-negative, four laminin alpha2-positive and seven
      partial laminin alpha2-deficient congenital muscular dystrophy (CMD) patients,
      and compared it to Duchenne muscular dystrophy (DMD) patients and controls. TGF
      beta1 mRNA levels in skeletal muscle from laminin alpha2-negative and laminin
      alpha2-positive CMD patients were significantly greater than in controls (P <
      0.05 and P < 0.005, respectively), while in partial laminin alpha2-deficient
      muscular dystrophy patients the amount was not significantly higher than in
      controls (P > 0.1). The TGF-beta1 values were lower than those found in DMD,
      although the extent of fibrosis was greater in CMD than in DMD and controls. Our
      findings suggest that TGF-beta1 is involved in CMD muscle fibrosis, but
      differently from what we observed in DMD muscles as it seems not to be the major
      player in connective tissue proliferation.

PMID- 10063833
TI  - A nonsense mutation in the myophosphorylase gene in a Japanese family with
      McArdle's disease.
AB  - We identified a new mutation in the myophosphorylase gene in a Japanese family
      with McArdle's disease. This point mutation results in the replacement of a
      tryptophan at amino acid position 361 with a stop codon, the third nonsense
      mutation in this disorder. Our findings further expand the already wide spectrum
      of genetic lesions associated with McArdle's disease, and establish that
      molecular genetic heterogeneity is also present in the Japanese population.

PMID- 10063834
TI  - IgM paraproteinemia in a patient with primary lateral sclerosis.
AB  - Primary lateral sclerosis is an uncommon, distinct clinical entity. We report a
      patient with primary lateral sclerosis in whom investigations revealed an IgM
      monoclonal gammopathy, raised CSF protein and persistently high ESR. A number of
      reports suggest that lymphoproliferative disorders, paraproteinemia and clinico
      pathological syndromes mimicking motor neuron diseases may be associated. We
      discuss the clinical features noted in our patient in relation to these reports,
      and the possible pathogenetic mechanisms.

PMID- 10063835
TI  - Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X
      linked myotubular myopathy patients.
AB  - X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder mainly
      affecting newborn males. Neonatal muscle weakness and hypotonia usually leads to
      a rapid demise. The responsible gene, MTM1, was isolated in 1996, and mutational
      data derived from 90 patients have been published. We report on our findings in a
      further 53 patients, using genomic DNA and mRNA screening protocols. Thirty-four
      novel mutations were identified in 37 cases, and six known mutations found in 10
      other patients. The 34 new mutations include five large deletions, eight
      nonsense, six frameshift, five missense, and eight splice-site mutations, whereas
      two intronic variants causing partial exon skipping represent the first report on
      such a mechanism in MTM1. Two deletions, one involving exon 1, and the second
      exon 15, are the first defects to be identified in these exons. The heterogeneity
      of the mutations, their mutational origins, and the varied ethnic backgrounds of
      the patients, indicate that the majority of XLMTM families are affected by unique
      MTM1 mutations.

PMID- 10063836
TI  - Structural congenital myopathies (excluding nemaline myopathy, myotubular
      myopathy and desminopathies): 56th European Neuromuscular Centre (ENMC) sponsored
      International Workshop. December 12-14, 1997, Naarden, The Netherlands.

PMID- 10063837
TI  - Neuromuscular disorders: gene location.

PMID- 10063838
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 10063839
TI  - The Academy of Radiology Research.

PMID- 10063840
TI  - Malpractice issues in radiology. Y2K.

PMID- 10063841
TI  - A low-cost, full-function picture archiving and communication system using
      standard PC hardware and the traditional 4-over-4 display format.
AB  - OBJECTIVE: With a 12-year background of our completely digital nuclear medicine
      picture archiving and communication system (PACS), we have recently implemented a
      novel PACS, OpenPACS, which can be used for interpretation and display of CT, MR
      imaging, sonography, nuclear medicine, and computed and digital radiography
      studies. OpenPACS uses low-cost standard PC hardware and software that is widely
      available and is readily serviced and maintained. The OpenPACS application
      program is available over the Internet. CT or MR imaging slices from one or
      multiple studies can be presented simultaneously or in cine mode on a wall-sized
      multimonitor display. The assembly, with a total resolution of 6400 x 4800
      pixels, resembles a traditional array of eight standard X-ray viewboxes. A
      wireless mouse is used to vary attenuation and other display parameters. Multiple
      backup and redundancy are provided. Currently, six CT and six MR imaging scanners
      of different vendors are networked to OpenPACS, which is also networked to our
      nuclear medicine PACS. CONCLUSION: After only a brief introduction, radiologists
      rapidly become familiar with the system because it is based on the use of
      standard Windows icons and procedures and offers a display that resembles a
      standard X-ray film presentation.

PMID- 10063842
TI  - CT colonography: value of scanning in both the supine and prone positions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of CT
      colonography when patients were imaged in both the supine and prone positions. We
      evaluated whether imaging in two positions decreased the number of collapsed
      colonic segments and increased sensitivity for polyp detection. MATERIALS AND
      METHODS: Twenty-three patients underwent CT colonography in both the supine and
      prone positions. Colonic distention for each of the 46 scans was graded. Adequacy
      of distention for either position alone was compared with that of the combination
      of the two positions. Polyp data revealed by colonoscopy were reviewed, and the
      CT data were then retrospectively reviewed for polyp detection. RESULTS: When
      each scan was considered alone without benefit of the scan obtained in the
      opposite position, 27 (58.7%) of 46 scans showed inadequate distention. When
      scans obtained in both positions were considered together, 20 (87.0%) of 23
      patients had adequate distention with the grading system used. However, this
      value increased to 23 (100%) of 23 patients when the reasons for inadequate
      distention in the three patients were considered. Of the 27 polyps detected with
      colonoscopy, 21 (77.8%) were also detected retrospectively with CT colonography.
      Colonoscopy showed 20 polyps that were 5 mm or larger; nineteen (95.0%) of these
      20 polyps were also detected retrospectively with CT colonography, nine (47.4%)
      of which were seen in only one position. CONCLUSION: Use of both the supine and
      prone positions for patients undergoing CT colonography improves evaluation of
      the colon and increases sensitivity for polyp detection.

PMID- 10063843
TI  - Acute diverticulitis of the cecum and ascending colon: thin-section helical CT
      findings.
AB  - OBJECTIVE: Our objective was to describe thin-section helical CT findings of
      acute diverticulitis of the cecum and ascending colon in 12 patients. CONCLUSION:
      Thin-section helical CT is able to reveal inflamed diverticula in acute
      diverticulitis of the cecum and ascending colon, which are diagnostic of this
      disease. Preservation of the enhancing pattern of the colonic wall was the most
      common helpful ancillary finding.

PMID- 10063844
TI  - Pancreatic-phase versus portal vein-phase helical CT of the pancreas: optimal
      temporal window for evaluation of pancreatic adenocarcinoma.
AB  - OBJECTIVE: Our objective was to use helical CT to compare the enhancement
      attenuation values of pancreatic adenocarcinoma, adjacent normal pancreas, and
      critical vascular structures during the pancreatic phase and portal vein phase.
      SUBJECTS AND METHODS: Forty-one patients with pathologically proven pancreatic
      adenocarcinoma underwent dual-phase thin-section dynamic helical CT using a
      pancreatic-phase and portal vein-phase protocol. The scan delay after initiation
      of the contrast bolus was 40 sec for the pancreatic phase and 70 sec for the
      portal vein phase. Attenuation values after i.v. contrast administration were
      calculated during both phases of scanning for normal pancreas, pancreatic tumor,
      celiac axis, superior mesenteric artery, superior mesenteric vein, splenic vein,
      and portal vein. Quantitative values were assessed using regions of interest.
      RESULTS: Mean differences of enhancement between tumor and normal pancreas were
      significantly greater in the pancreatic phase (57 H) than the portal vein phase
      (35 H) (p = .0001). Enhancement values of all the critical vascular structures
      were also significantly greater in the pancreatic phase than the portal vein
      phase (p < .001). CONCLUSION: With dynamic thin-section helical CT, pancreatic
      phase scanning provides greater differences in contrast enhancement between
      normal pancreas and pancreatic tumor and between pancreatic tumors and
      surrounding critical vascular structures than does portal vein-phase scanning.

PMID- 10063845
TI  - Acute pancreatitis complicated by gland necrosis: spectrum of findings on
      contrast-enhanced CT.

PMID- 10063846
TI  - Assessment of pancreatic invasion in patients with advanced gastric carcinoma:
      usefulness of the sliding sign on sonograms.
AB  - OBJECTIVE: The purpose of our study was to determine the value of the sliding
      sign on sonograms in evaluating direct pancreatic invasion of advanced gastric
      carcinoma. SUBJECTS AND METHODS: Sonography was performed prospectively on 70
      patients with pathologically proven advanced gastric carcinoma. Sonography was
      directed at the detection of motion between the gastric mass and the pancreas.
      When the gastric mass showed complete sliding motion against the pancreas or
      partial sliding motion with a preserved echogenic fat plane between the two
      organs on respiration or on extrinsic compression with a transducer (positive
      sliding sign), patients were considered to have no pancreatic invasion. When the
      gastric mass had no sliding motion against the pancreas or partial sliding motion
      with a disrupted echogenic fat plane between the two organs (negative sliding
      sign), patients were considered to have pancreatic invasion. After sonography,
      all patients underwent surgery and the results of sonography were compared with
      the findings at surgery and pathology. RESULTS: Of the 70 patients, 17 had
      pancreatic invasion and 53 had no evidence of pancreatic invasion at surgery and
      pathology. The sliding sign on sonography yielded an 80% sensitivity, 96%
      specificity, and 90% accuracy for the diagnosis of pancreatic invasion.
      CONCLUSION: Application of the sliding sign on sonography was simple and highly
      accurate in the diagnosis of pancreatic invasion by advanced gastric carcinoma.
      The sliding sign may prove useful in the preoperative detection of pancreatic
      invasion by gastric carcinoma when CT has been inconclusive.

PMID- 10063847
TI  - Tuberculosis versus lymphomas in the abdominal lymph nodes: evaluation with
      contrast-enhanced CT.
AB  - OBJECTIVE: Tuberculosis in the abdominal lymph nodes may be difficult to
      distinguish from lymphomas. This study evaluated specific CT imaging criteria for
      differentiating these entities. MATERIALS AND METHODS: We retrospectively
      reviewed the anatomic distribution and CT enhancement patterns of disease in 69
      patients, 26 (38%) with tuberculosis and 43 (62%) with untreated lymphomas
      involving abdominal lymph nodes. Of the patients with tuberculosis, five (19%)
      had disseminated disease and 21 (81%) had nondisseminated disease. Of the
      patients with lymphomas, 16 (37%) had Hodgkin's disease and 27 (63%) had non
      Hodgkin's lymphoma. RESULTS: Disseminated and nondisseminated tuberculosis
      involved predominantly lesser omental, mesenteric, anterior pararenal, and upper
      paraaortic lymph nodes. Lower paraaortic lymph nodes were involved more often in
      Hodgkin's disease (15 patients [94%]), non-Hodgkin's lymphoma (24 patients
      [89%]), and disseminated tuberculosis (five patients [100%]) than in
      nondisseminated tuberculosis (one patient [5%]). Mesenteric lymph nodes were
      involved more often in disseminated tuberculosis (four patients [80%]) and
      nondisseminated tuberculosis (11 patients [52%]) than in Hodgkin's disease (one
      patient [6%]) (p < .01). Anatomic distribution was not different between
      disseminated tuberculosis and non-Hodgkin's lymphoma. Tuberculous lymphadenopathy
      commonly showed peripheral enhancement, frequently with a multilocular
      appearance, whereas lymphomatous adenopathy characteristically showed homogeneous
      attenuation (14 patients [87.5%] with Hodgkin's disease and 19 patients [70%]
      with non-Hodgkin's lymphoma [p < .01]). CONCLUSION: Our findings indicate that
      the anatomic distribution and specific enhancement patterns of lymphadenopathy
      seen on contrast-enhanced CT can be useful in differentiating between
      tuberculosis and untreated lymphomas of the abdominal lymph nodes.

PMID- 10063848
TI  - Sclerosing mesenteritis: imaging findings in 17 patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the radiologic findings of
      sclerosing mesenteritis and to describe certain signs that suggest the diagnosis.
      CONCLUSION: Sclerosing mesenteritis represents a single disease with two
      radiologically different variants. In an appropriate clinical setting, radiologic
      features can suggest the diagnosis, delineate the extent of the process, and
      prescribe or limit surgical procedures. The "fat ring" sign and the presence of a
      tumoral pseudocapsule are important findings for the diagnosis of the disease.

PMID- 10063849
TI  - Correlation of duplex sonography findings and portal pressure in 375 patients
      with portal hypertension.
AB  - OBJECTIVE: The purpose of this study was to determine the potential usefulness of
      duplex sonography in the grading of portal hypertension. SUBJECTS AND METHODS:
      Duplex sonography of the portal vein system and measurement of the portal
      pressure and portosystemic pressure gradient were performed in 375 patients
      before placement of transjugular intrahepatic portosystemic shunts. Subgroups
      included patients with recent variceal bleeding (n = 296) and patients with
      refractory ascites without previous variceal bleeding (n = 79). A matched cohort
      of 100 patients without portal hypertension was also examined. Differences
      between the groups in portal and splenic vein diameter, flow velocity, congestion
      index, and hepatic arterial resistive index were assessed using the Wilcoxon rank
      sum test. RESULTS: Compared with healthy individuals, our patients had an
      increased portal vein diameter (+30%, p < .001), decreased portal vein flow
      velocity (-44%, p < .001), and increased congestion index (+185%, p < .001). A
      portal vein diameter greater than 1.25 cm or a portal vein flow velocity less
      than 21 cm/sec indicated portal hypertension with a sensitivity and specificity
      of 80%. If the congestion index exceeded 0.1, portal hypertension was diagnosed
      with a 95% sensitivity and specificity. The portal pressure and gradient
      correlated only weakly (r < .2, p < .05) with sonographic variables. Using
      multivariate analysis, subgroups with variceal bleeding or refractory ascites did
      not show differences in hemodynamics, including pressures. CONCLUSION: Duplex
      sonography contributes to the diagnosis of portal hypertension but does not allow
      its grading. Similarity of portal hemodynamics between patients with variceal
      bleeding and patients with refractory ascites suggests that additional factors
      determine the respective clinical presentation.

PMID- 10063850
TI  - Percutaneous microwave hepatic tumor coagulation with segmental hepatic blood
      flow occlusion in seven patients.
AB  - OBJECTIVE: We assess the usefulness of microwave hepatic tumor coagulation
      therapy with balloon occlusion of segmental hepatic blood flow for eight
      recurrent metastatic hepatic tumors in seven patients. CONCLUSION: Limited early
      experience with microwave hepatic tumor coagulation therapy and segmental hepatic
      blood flow occlusion has been positive, suggesting that further clinical
      evaluation is warranted.

PMID- 10063851
TI  - Percutaneously implantable catheter-port system for chemotherapeutic infusion
      through the hepatic artery.
AB  - OBJECTIVE: The goal of this study was to determine the feasibility and outcomes
      of percutaneously implantable catheter-port system placement in the hepatic
      artery for the purpose of intraarterial chemotherapeutic infusion. CONCLUSION:
      Percutaneously implantable catheter-port system placement is safe and technically
      feasible for use in the hepatic artery. The implantation procedure is less
      invasive than surgical implantation of similar port systems.

PMID- 10063852
TI  - Pseudolesions of the liver possibly caused by focal rib compression: analysis
      based on hemodynamic change.
AB  - OBJECTIVE: The purpose of this study is to show and analyze the CT appearance of
      pseudolesions of the liver caused by rib compression and to discuss the possible
      mechanism on the basis of findings of incremental dynamic CT, CT during arterial
      portography, and CT hepatic arteriography. CONCLUSION: Focal compression of the
      liver caused by curved ribs can cause transient focal diminishment of portal
      venous perfusion without significantly altering hepatic arterial perfusion. Such
      diminishment may be observed as low-density areas on the early phase of
      incremental dynamic CT.

PMID- 10063853
TI  - Precaval draining vein from paraesophageal varices: radiologic-anatomic
      correlation.
AB  - OBJECTIVE: The purpose of this study was to describe the CT features of the
      precaval draining vein from paraesophageal varices in six patients with liver
      cirrhosis. We also assessed the anatomic nature of the vein. CONCLUSION: The
      precaval vein courses anteriorly to the inferior vena cava and drains into the
      right anterior aspect of the inferior vena cava. The diameter of the precaval
      vein ranged from 3 to 13 mm (mean, 6.5 mm). The precaval vein is anatomically
      identical to the anastomosis between the right and left inferior phrenic veins.

PMID- 10063854
TI  - Percutaneous transhepatic creation of a choledochojejunostomy between an excluded
      aberrant bile duct and a Roux-en-Y limb.

PMID- 10063855
TI  - Hepatic arterial supply from the cystic artery: findings on arteriography, CT
      arteriography, and CT during arterial portography.

PMID- 10063856
TI  - Percutaneous imaging-guided biopsy of the spleen.

PMID- 10063857
TI  - Safety and efficacy of catheter-directed thrombolysis for iliofemoral venous
      thrombosis.

PMID- 10063858
TI  - Cost comparison of radiologic versus surgical placement of long-term hemodialysis
      catheters.
AB  - OBJECTIVE: The purpose of this study was to compare the cost of radiologic versus
      surgical placement of long-term hemodialysis catheters. MATERIALS AND METHODS:
      Our cost analysis was based on 47 long-term hemodialysis catheters radiologically
      placed in 45 patients and 25 catheters surgically placed in 25 patients from
      October 1996 through March 1997. Variable and total costs were calculated using
      data from the hospital administrative computer system that records the actual
      costs incurred by the hospital in caring for patients. RESULTS: The average total
      hospital cost was $926 for each radiologic placement and $1849 for each surgical
      placement of long-term hemodialysis catheters. The total cost saving for
      radiologic placement was $923 for each catheter. CONCLUSION: Radiologic placement
      of long-term hemodialysis catheters resulted in substantial savings over surgical
      placement.

PMID- 10063859
TI  - Epithelial displacement after stereotactic 11-gauge directional vacuum-assisted
      breast biopsy.
AB  - OBJECTIVE: Displaced epithelial fragments at percutaneous biopsy of ductal
      carcinoma in situ (DCIS) may mimic stromal invasion. This study was undertaken to
      determine the frequency of epithelial displacement in DCIS lesions of patients
      who underwent stereotactic 11-gauge directional vacuum-assisted breast biopsy.
      MATERIALS AND METHODS: We retrospectively reviewed 28 consecutive DCIS lesions in
      patients who underwent stereotactic 11-gauge directional vacuum-assisted breast
      biopsy followed by surgery. Surgical specimens were examined for histologic
      evidence of epithelial displacement, consisting of fragments of epithelium in
      artifactual spaces in breast parenchyma or in lymphovascular channels,
      accompanied by hemorrhage, fat necrosis, inflammation, hemosiderin-laden
      macrophages, or granulation tissue. RESULTS: The median number of specimens
      obtained per lesion was 14 (range, seven to 45). The median interval from
      stereotactic biopsy to surgery was 27 days (range, 10-59 days). Surgery revealed
      DCIS in 19 (68%) of 28 lesions, DCIS and infiltrating carcinoma in four lesions
      (14%), and no residual carcinoma in five lesions (18%). Reactive changes at the
      biopsy site were identified in all cases. Displacement of benign epithelium into
      granulation tissue at the stereotactic biopsy site was identified in two cases
      (7%). We found no evidence of displacement of malignant epithelium. CONCLUSION:
      Epithelial displacement is uncommon after stereotactic 11-gauge directional
      vacuum-assisted biopsy of the breast. We observed displacement of benign
      epithelium in two (7%) of 28 DCIS lesions and no displacement of malignant
      epithelium.

PMID- 10063860
TI  - Comparison of rebiopsy rates after stereotactic core needle biopsy of the breast
      with 11-gauge vacuum suction probe versus 14-gauge needle and automatic gun.
AB  - OBJECTIVE: The 11-gauge vacuum suction probe is an alternative to the 14-gauge
      needle and automatic gun for performing stereotactic core needle biopsies. This
      study compares rebiopsy rates after stereotactic core needle biopsies that were
      performed with the two methods. The study also assesses the outcomes of those
      repeat biopsies. MATERIALS AND METHODS: Five hundred ninety-two stereotactic core
      needle biopsies using a 14-gauge needle and automatic gun and 354 using an 11
      gauge vacuum suction probe were performed consecutively. Excluding malignancies,
      the number of cases requiring rebiopsy and the reasons for rebiopsy were
      determined for each group. The histologic diagnoses of the repeat biopsies were
      assessed. RESULTS: The rebiopsy rate was significantly lower with the 11-gauge
      vacuum suction probe (9.0%) than with the 14-gauge needle and automatic gun
      (14.9%) (p = .013). Significant reductions were found in cases of insufficient
      sampling (probe, 1.7%; needle, 4.4%; p = .042) and mammographic-pathologic
      discrepancy (probe, 0.8%; needle, 3.4%; p = .026). The rebiopsy rate for masses
      was 6.1% with the vacuum probe versus 10.7% with the 14-gauge needle (p = .12)
      and for calcifications was 11.6% with the vacuum probe versus 23.7% with the 14
      gauge needle (p = .003). After rebiopsy, the percentage of cases in which
      malignancy was found was 18.5% with the vacuum probe versus 13.7% with the 14
      gauge needle. On rebiopsy, the percentage of malignancies found in each category
      were atypical hyperplasia: probe 26.7%, needle 20.0%; insufficient sample: probe
      0%, needle 9.5%; pathologist recommendation: probe 50.0%, needle 12.5%; and
      lobular carcinoma in situ: probe 0%, needle 100%. CONCLUSION: Use of the 11-gauge
      vacuum-assisted device significantly decreases but does not eliminate the need
      for rebiopsy after stereotactic core needle biopsy. The rebiopsy rate for
      calcifications was significantly reduced by using the vacuum suction probe rather
      than the 14-gauge needle; however, the rate for masses was reduced only slightly.
      On rebiopsy, malignancies were found in both groups.

PMID- 10063861
TI  - Decubitus stereotactic core biopsy of the breast: technique and experience.

PMID- 10063862
TI  - Methods of compliance with Mammography Quality Standards Act regulations for
      tracking positive mammograms: survey results.
AB  - OBJECTIVE: We sent a questionnaire to fellows of the Society of Breast Imaging to
      determine how breast imaging facilities comply with regulations mandated by the
      Mammography Quality Standards Act for tracking patients whose mammograms show
      positive findings. SUBJECTS AND METHODS: We surveyed the Society of Breast
      Imaging fellows to determine practice types, follow-up methodology, additional
      time and personnel required, and end points of radiologists' responsibility for
      follow-up of mammograms with positive findings. RESULTS: Forty-six (68%) of 68
      surveyed practices responded, including 21 academic, 16 private, and nine mixed
      practices that averaged 15,761 mammograms a year (range, 300-50,000). The 46
      practices used computers (n = 30) or handwritten paper (n = 16) audits.
      Radiologists (n = 8), technologists (n = 6), other personnel (n = 10), or a
      combination (n = 22) tracked procedures and patients with abnormal mammographic
      results. Average time spent tracking was given as a few hours a week (n = 28), 2
      4 hr a day (n = 11), and 40 hr a week (n = 5). The remaining two practices
      indicated that less than 1 hr per month was required (n = 1) or that they used
      two full-time data managers (n = 1). Accepted tracking end points included
      surgical biopsy (n = 30), referring physician recommended other management (n =
      16), patient refused recommendation (n = 27), medical care transfer (n = 27),
      patient moved (n = 22), or patient lost to referring physician follow-up (n =
      16). CONCLUSION: Among dedicated mammographers, the methodology in the task of
      tracking patients with positive findings on mammography varies. All methodologies
      described in responses to our survey involved considerable time and effort.

PMID- 10063863
TI  - Motion artifact seen on slot-scanning direct digital mammography.
AB  - OBJECTIVE: Our goal was to determine the appearance of motion artifact when
      imaging an anthropomorphic breast phantom using a digital slot-scanning system
      compared with a screen-film system. MATERIALS AND METHODS: Digital and screen
      film images were obtained during both brief and continuous manually induced
      motion of an anthropomorphic phantom in four directions. Continuous motion was
      further characterized using a syringe pump to induce motion artifact. RESULTS: On
      screen-film images, brief motion caused degradation of the entire image,
      simulating a double exposure. Conversely, on digital images using a slot-scanning
      system, brief motion caused degradation of only a small portion of the image.
      Continuous motion resulted in smearing of phantom details with both systems,
      although the smearing was more strongly influenced by the direction of motion
      when the slot-scanning system was used. With the slot-scanning system, motion in
      the direction of the detector sweep resulted in elongated distortion, whereas
      motion in the opposite direction resulted in foreshortening; diagonal smearing
      was seen with perpendicular phantom motion. The magnitude of distortion for
      continuous motion at a set velocity was substantially less with the slot-scanning
      system. CONCLUSION: Motion artifact with a slot-scanning direct digital
      mammography unit differs significantly from that seen with a conventional screen
      film unit and, despite a relatively long overall exposure, may prove to be less
      of a problem than with conventional units because any given part of an object is
      exposed only briefly.

PMID- 10063864
TI  - Intracranial internal carotid artery angioplasty: technique with clinical and
      radiographic results and follow-up.
AB  - OBJECTIVE: Our objective is to describe the use of percutaneous transluminal
      angioplasty in eight patients with symptomatic high-grade atherosclerotic
      intracranial internal carotid artery stenoses. We describe our technique for
      performing the procedure and clinical and radiographic follow-up for an average
      of 53 months to determine the long-term results. CONCLUSION: Percutaneous
      transluminal angioplasty was shown to be an efficacious treatment for symptomatic
      intracranial internal carotid artery atherosclerotic disease in our group of
      patients.

PMID- 10063865
TI  - Acute vertebrobasilar occlusion: treatment with high-dose intraarterial
      urokinase.
AB  - OBJECTIVE: The purpose of this study was to describe our successful experience
      with high-dose intraarterial urokinase therapy in treating acute, life
      threatening vertebrobasilar occlusion. CONCLUSION: We successfully treated five
      patients with acute vertebrobasilar occlusion who presented up to 24 hr after the
      onset of symptoms. Higher doses of urokinase than are commonly reported in the
      literature were used in this series at a rapid infusion rate with a "pulse-spray"
      technique. The result was prompt thrombolysis and good clinical outcome.

PMID- 10063866
TI  - Intracranial germinomas: correlation of imaging findings with tumor response to
      radiation therapy.
AB  - OBJECTIVE: The purpose of this study was to correlate imaging characteristics of
      intracranial germinomas with response to radiation therapy. MATERIALS AND
      METHODS: Using tumor size at the completion of irradiation, we classified 23
      patients with histologically proven germinomas in the pineal gland (n = 6), the
      suprasellar region (n = 7), and the basal ganglia (n = 10) into two groups:
      excellent response group (n = 14) and good response group (n = 9). Excellent
      response was defined as complete resolution or residual tumor less than 1.0 cm in
      diameter, and good response was defined as residual tumor of 1.0-3.0 cm in
      diameter. CT (n = 53) and MR (n = 32) images obtained before, during, and after
      radiation therapy were retrospectively analyzed with particular attention to the
      location, size, presence of cystic change, and CSF seeding of the tumors.
      RESULTS: In all 23 patients, the tumors decreased 85-100% in size at the
      completion of irradiation with 40-56 Gy. A significant factor in the different
      responses to irradiation between patients in the excellent and good response
      groups was cystic change of the tumor. Tumors with cystic components responded
      more slowly and had larger residual lesions than did tumors without cystic
      components (p < .01). In eight of 12 cystic tumors, the cystic portion of the
      tumor responded more slowly than did the solid portion and remained visible on
      imaging 6-12 months after irradiation. We found no significant differences
      between the two groups in location, size, and CSF seeding of tumors. In 12
      patients with residual lesions at the completion of irradiation, the tumors
      proceeded to resolve after completion of treatment. CONCLUSION: In our study,
      tumor response to radiation therapy correlated negatively with the presence of a
      cystic region.

PMID- 10063867
TI  - Sublingual gland: MR features of normal and diseased states.
AB  - OBJECTIVE: We describe the MR features of the sublingual gland in normal and
      diseased states. SUBJECTS AND METHODS: We used MR imaging to assess age-related
      changes in size and signal intensity of normal sublingual glands in 60 control
      subjects. The MR features of sublingual glands were also studied in 70 patients
      with cancer, cellulitis of the sublingual space, Sjogren's syndrome, or ranula.
      RESULTS: MR imaging efficiently revealed normal sublingual glands. On T1-weighted
      images, the MR signal intensity of the sublingual gland was lower than that of
      the surrounding fat but higher than that of muscle. The sublingual glands showed
      age-related decreases in size, with approximately 25% of the thickness present in
      the second decade of life being lost by the seventh decade. T1-weighted signal
      intensity of the parotid gland increased with age, but the signal intensity of
      the sublingual and submandibular glands did not. T1-weighted signal intensity of
      carcinomas in and near the sublingual space was lower than that of the sublingual
      glands, but T2-weighted signal intensity of carcinomas exceeded that of the
      glands. Gadolinium enhancement occasionally diminished the contrast between
      invading carcinomas and the glands. T1-weighted MR imaging showed that sublingual
      glands affected by Sjogren's syndrome exhibit features analogous to those of the
      other major salivary glands; however, the sublingual glands seemed to be less
      severely involved overall in this syndrome than the other major glands. We found
      that using fat suppression and short inversion time inversion recovery may be
      useful for assessment of sialadenitis of the gland. CONCLUSION: MR imaging is
      useful in depicting normal and diseased states of the sublingual gland.

PMID- 10063868
TI  - Fluoroscopically guided percutaneous needle biopsy of the cervical spinal cord.

PMID- 10063869
TI  - MR imaging in patients with epicardial pacemaker wires.

PMID- 10063870
TI  - CT findings of pulmonary artery aneurysms during treatment for Behcet's disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate the CT findings of pulmonary
      artery aneurysms in patients being treated for Behcet's disease. MATERIALS AND
      METHODS: Thirteen patients with Behcet's disease who had a total of 46 aneurysms
      were included in the study. All patients underwent helical CT before and after
      treatment. Both initial and follow-up CT scans were evaluated for location,
      number, and size of aneurysms and for thrombosis and pulmonary parenchyma
      changes. RESULTS: Thirty-five (76%) of the 46 aneurysms completely disappeared
      during the 3-42 months of treatment (mean, 21 months), and the remaining 11
      aneurysms (24%) became smaller. Both disappearance and regression of aneurysms
      were preceded by thrombus formation. In 15 initially thrombosed aneurysms (33%),
      the thrombus increased in size during treatment. After treatment, the thrombus
      regressed and the pulmonary artery aneurysms disappeared. Thirty-one initially
      nonthrombosed aneurysms (67%) first became thrombosed during treatment; later,
      the thrombus regressed and the aneurysm decreased in size. Perianeurysmal
      consolidation and air-space nodules detected in seven patients disappeared in the
      early stages of treatment. Mosaic attenuation areas were seen in eight patients
      and disappeared in seven (88%) after treatment. CONCLUSION: Pulmonary artery
      aneurysms in Behcet's disease may become smaller or disappear with medical
      treatment. Mural thrombotic changes may be observed during the regression of
      pulmonary artery aneurysms. Helical CT is helpful in the diagnosis and follow-up
      of aneurysms and thrombosis in Behcet's disease.

PMID- 10063871
TI  - Pulmonary injury from proton and conventional radiotherapy as revealed by CT.
AB  - OBJECTIVE: Although radiation therapy is used in early-stage inoperable lung
      cancer, it often results in injury to functional lung tissue. A study was
      undertaken to determine the frequency and severity of pulmonary injury revealed
      by CT in patients who had undergone conformal proton (to a limited volume)
      radiation therapy. We compared these findings with those from a group of patients
      who had undergone a combination of photon and conformal proton (to a larger
      volume) radiation therapy. CONCLUSION: Proton radiation therapy was associated
      with a lower frequency of pulmonary injury than the combined regimen. Injury
      correlated well with the volume of normal lung that was irradiated. Conformal
      proton radiation therapy appears to be able to reduce the incidence and severity
      of pulmonary injury revealed by CT.

PMID- 10063872
TI  - Variant bronchial anatomy: CT appearance and classification.

PMID- 10063873
TI  - Follicular hyperplasia of bronchus-associated lymphoid tissue causing severe air
      trapping.

PMID- 10063874
TI  - Miliary tuberculosis after intravesical bacille Calmette-Guerin immunotherapy for
      carcinoma of the bladder.

PMID- 10063875
TI  - Using gadolinium-enhanced three-dimensional MR angiography to assess arterial
      inflow stenosis after kidney transplantation.
AB  - OBJECTIVE: Our objective was to evaluate use of gadolinium-enhanced three
      dimensional (3D) MR angiography in the assessment of suspected arterial inflow
      stenosis after kidney transplantation. SUBJECTS AND METHODS: Twenty-eight
      consecutive patients receiving kidney transplants (26 single-kidney transplants
      and two en block transplants) with suspected arterial inflow stenosis were
      examined with two MR angiography sequences: gadolinium-enhanced 3D fast spoiled
      gradient-recalled (SPGR) imaging and 3D phase-contrast imaging. Twenty-four of
      these patients then were examined using the gold standards: either digital
      subtraction angiography (DSA) (n = 23) or surgery (n = 1). MR angiography and DSA
      studies were independently and prospectively analyzed for the presence of
      arterial stenoses (mild [<50%], severe [50-90%], or critical [>90%]) in the
      iliac, anastomotic, and renal artery segments. Two independent observers
      retrospectively evaluated the MR angiography sequences for ability to detect or
      exclude significant (> or = 50%) arterial stenoses. RESULTS: In 22 single-kidney
      transplants, DSA showed eight significant stenoses in 66 arterial segments. MR
      angiograms adequately showed 66 of 66 segments (prospective observers) and 64 of
      66 segments (each retrospective observer), which were subsequently evaluated. The
      sensitivity and specificity of MR angiography in revealing significant stenoses
      were 100% and 98% (prospective analysis), 88% and 98% (retrospective observer 1),
      and 86% and 100% (retrospective observer 2). Concordance between observers showed
      kappa values exceeding .85 for all comparisons except the analysis of phase
      contrast series (kappa = .62). In one en block transplant, DSA showed that
      stenosis was greater than 90%, although it had been graded at less than 50% with
      MR angiography. CONCLUSION: Gadolinium-enhanced 3D MR angiography accurately
      evaluated arterial inflow in single-kidney transplants.

PMID- 10063876
TI  - Sonographic detection of uterine and ovarian abnormalities in female survivors of
      Wilms' tumor treated with radiotherapy.
AB  - OBJECTIVE: The purpose of this study was to use sonography to evaluate the size
      of the ovaries and uterus in survivors of Wilms' tumor who underwent
      radiotherapy. SUBJECTS AND METHODS: Eighteen survivors of Wilms' tumor had their
      ovaries and uterus measured on sonography. Their ages at diagnosis and treatment
      ranged from 14 months to 6 years. Four girls were prepubertal (age, 5-9 years),
      11 were postpubertal (age, 11-30 years), and three had primary ovarian failure
      (age, 15-23 years) at the time of imaging. Findings were compared with those of a
      control group of 25 prepubertal and 25 postpubertal girls and women. Gonadotropin
      levels were measured. RESULTS: Three patients who underwent whole abdomen
      radiotherapy had elevated levels of gonadotropin and primary ovarian failure.
      Neither ovary was seen in two of the three patients and both ovaries were
      abnormally small (< or = 1 cm3) in the third patient. The uterus was abnormally
      small (length, < or = 4 cm) in all three of these patients even though two were
      being treated with hormone replacement therapy. Ten postpubertal patients who
      underwent hemiabdomen radiotherapy had normal gonadotropin levels and a normal
      sized uterus on sonography; the ovary on the side that received radiotherapy was
      not seen in three of the 10 patients or was abnormally small (< or = 1.4 cm3) in
      two of the 10 patients compared with all normal ovaries in the postpubertal
      control group (p < .0001). One postpubertal patient with bilateral renal bed
      radiotherapy had normal ovaries and a normal-sized uterus. Significantly more
      patients in the postpubertal and ovarian failure radiotherapy group (5 [36%] of
      14 patients) had one or both ovaries not seen than the control group (none [0%]
      of 25 patients; p = .0014). The uterus was significantly smaller than normal in
      three (23%) of the 13 patients in the postpubertal hemiabdomen and ovarian
      failure radiotherapy group versus none of the 25 patients in the postpubertal
      control group (p = .0339). CONCLUSION: Postpubertal female survivors of Wilm's
      tumor who underwent radiotherapy as children may have one or two small or absent
      ovaries and a small uterus that can be detected by sonography. The response of
      the uterus to hormone replacement therapy can also be assessed on sonography.

PMID- 10063877
TI  - Radiologic usefulness of hysterosalpingography after bladder filling.

PMID- 10063878
TI  - Carcinosarcoma of the urinary bladder.

PMID- 10063879
TI  - Sonographic diagnosis of a traumatic intraperitoneal bladder rupture.

PMID- 10063880
TI  - Primary leiomyosarcoma of bone.
AB  - OBJECTIVE: This study describes radiographic and MR imaging features of primary
      leiomyosarcoma of bone. SUBJECTS AND METHODS: Twelve patients (five men and seven
      women, 39-79 years old) who were treated at two oncology centers for primary
      leiomyosarcoma of bone involving the femurs, tibia, ilium, and inferior pubic
      ramus were studied. None of the patients had preexisting disease or disease
      elsewhere at the time of diagnosis. Pathologic diagnosis was obtained in all
      patients. RESULTS: Radiographs of all patients showed a matrix that was
      exclusively osteolytic. In long bones (seven patients), the tumor had an average
      length of 11 cm (range, 7-17 cm) and revealed an elongated configuration. In the
      pelvis (five patients), the average length of the tumor was 10 cm (range, 4-15
      cm). MR imaging confirmed an intramedullary lesion in all patients, with
      extension into the soft tissues in eight patients and no identifiable soft-tissue
      mass in the remaining four patients. Four of the five pelvic tumors had a
      prominent soft-tissue mass, whereas only four of the seven long bone lesions
      revealed a soft-tissue mass that was, in all instances, small. The tumor was
      hypointense on T1-weighted images and showed heterogeneous signal intensity on T2
      weighted conventional and fast spin-echo sequences. We saw low signal intensity
      (short T2) in eight patients and homogeneous hyperintense signal intensity in one
      patient. In the remaining three patients, T2-weighted spin-echo sequences
      obtained with fat saturation showed high signal intensity (long T2) in the
      tumors. CONCLUSION: Primary leiomyosarcoma of bone is a rare tumor that on
      radiography reveals no matrix and on MR imaging reveals areas of T2 shortening in
      relation to fat on conventional and fast spin-echo sequences.

PMID- 10063881
TI  - Pseudosparing of the endplate: a potential pitfall in using MR imaging to
      diagnose infectious spondylitis.
AB  - OBJECTIVE: The objective of this study was to describe a potential pitfall in
      using MR imaging to diagnose infectious spondylitis called "pseudosparing" of the
      endplate, in which the diseased endplate appears to be better defined than a
      healthy endplate. CONCLUSION: Poor definition of the endplate is a classic
      radiographic finding in infectious spondylitis; on MR imaging, however, increased
      conspicuity, or "pseudosparing," was common in our study. Pseudosparing occurs
      when the normal chemical shift artifact seen in healthy endplates is lost as a
      result of infiltration of the bone marrow by a pathologic process.

PMID- 10063882
TI  - Evaluation of soft-tissue masses using segmented color Doppler velocity images:
      preliminary observations.
AB  - OBJECTIVE: We report our initial experience with segmented color Doppler velocity
      based estimates of tumor vascularity for various histogically proven soft-tissue
      masses. SUBJECTS AND METHODS: Color Doppler sonography of 23 histologically
      proven masses in 22 patients was performed. Digital color Doppler images were
      acquired directly off the scanner output or from video recordings and stored on a
      personal computer as 24-bit gray-scale and color composite images. A color
      Doppler velocity segmentation and analysis algorithm was applied to the digital
      images, from which we calculated the normalized percentage of color Doppler area.
      Normalization was determined by expressing color Doppler area as a percentage of
      the area enclosed by a preselected region of interest. We also calculated mean
      percentage, SD, and cumulative distribution of color Doppler area, relative to a
      fixed threshold, for the acquired image data sets. RESULTS: Estimates of mean
      percentage of color Doppler area showed a dynamic range of at least two or three
      orders of magnitude between lowest and highest values obtained. A scatterplot of
      mean percentage of color Doppler area versus SD of percentage of color Doppler
      area showed a linear monotonic relationship (r2 = .92), illustrating increasing
      vascular heterogeneity with mean vascularity. Preliminary data also suggest the
      presence of at least two distinct groups of masses (p < .0001) based on these
      vascularity estimates. One group corresponds to high-grade lesions in which tumor
      angiogenesis is expected to be important in predicting biologic behavior. The
      second group appeared to have little or no relationship to tumor vascularity or
      was of an intermediate (or lower) histologic grade. CONCLUSION: Quantitative
      color Doppler estimates of tumor vascularity can be obtained over a wide dynamic
      range. Such estimates provide a mechanism to assess vascular heterogeneity of
      soft-tissue tumors. Preliminary data suggest that two biologically distinct
      groups of masses may be separable on the basis of quantitative velocity-based
      estimates of tumor vascularity as obtained from color Doppler sonography.

PMID- 10063883
TI  - The hidden divot: a new type of incomplete fracture?

PMID- 10063884
TI  - Soft-copy versus hard-copy interpretation of voiding cystourethrography in
      neonates, infants, and children.
AB  - OBJECTIVE: Our aim is to determine whether agreement occurs between soft-copy (at
      a review workstation) and hard-copy (on laser-printed film) interpretations of
      fluoroscopic voiding cystourethrograms in neonates, infants, and children.
      SUBJECTS AND METHODS: Voiding cystourethrography was performed on 74 children
      (range, 2 weeks to 11 years old; mean, 3 years 6 months) for the evaluation of
      vesicoureteral reflux. The right and left ureters were scored separately by two
      observers on a scale of 0-5 using the international grading standard. Differences
      were tested for statistical significance with a marginal homogeneity test, and
      the strength of agreement was assessed using the kappa statistic. RESULTS: Of the
      148 ureters evaluated, 39 showed vesicoureteral reflux and 109 showed no
      vesicoureteral reflux on both soft copy and hard copy. For 128 of 148
      evaluations, interpretations of soft copy and hard copy produced agreement as to
      the grade of vesicoureteral reflux. For 11 of the 20 ureters with divergent
      interpretations, hard copy was scored one grade lower than soft copy; for the
      remaining nine ureters, hard copy was scored one grade higher than soft copy. No
      score differed by more than one grade. We found no statistically significant
      difference between soft-copy and hard-copy scores (p = .65), and agreement using
      the kappa statistic was substantial (.68). CONCLUSION: Soft-copy interpretation
      of voiding cystourethrograms is similar to hard-copy interpretation for
      vesicoureteral reflux.

PMID- 10063885
TI  - Lower pole reflux in children: uroradiologic appearances and pitfalls.

PMID- 10063886
TI  - Central venous catheter motion: a pitfall in catheter localization on pediatric
      chest radiography.
AB  - OBJECTIVE: We evaluated central venous catheter motion causing misinterpretation
      of catheter tip location in pediatric patients and in an experimental model.
      MATERIALS AND METHODS: After the recognition of clinically significant catheter
      motion in 12 randomly selected patients, we conducted a prospective 2-month study
      of chest radiographs in our pediatric care unit and neonatal emergency
      department. Serial radiographs were examined for change in catheter tip position
      ascribed to motion artifact. An in vitro model was developed to replicate
      clinical parameters. Experimentally, catheter movement and exposure time were
      analyzed and their impact on catheter localization was recorded. RESULTS: In the
      12 randomly selected patients, radiographic assessment of central venous catheter
      tip localization on sequential radiographs caused minor to major
      misinterpretation of the position of the catheter tip and even total
      nonvisualization of the catheter. Ten (3.5%) of 352 prospectively interpreted
      pediatric emergency department radiographs showed similar findings. Catheter
      motion that caused blurring was reproduced in vitro using radiographic parameters
      typically used in a clinical setting. CONCLUSION: Catheter motion can cause
      problems in assessing catheter tip position on pediatric emergency department
      chest radiographs. We reproduced this phenomenon in an in vitro model. Catheter
      removal or change in position may be mimicked by this artifact, and patient
      management may be affected. In our study, catheter localization was affected by
      catheter motion and exposure time.

PMID- 10063887
TI  - Helical CT amniography of congenital diaphragmatic hernia.
AB  - OBJECTIVE: Accurate prenatal diagnosis of congenital diaphragmatic hernia is
      important for perinatal planning and potential fetal surgery. We describe the
      application and usefulness of helical CT amniography in the evaluation of
      suspected congenital diaphragmatic hernia in three fetuses. CONCLUSION: Helical
      CT amniography is an efficient means for evaluation of congenital diaphragmatic
      hernia. Accurate diagnosis was made in all three patients.

PMID- 10063888
TI  - Fetal CNS anomalies revealed on ultrafast MR imaging.

PMID- 10063889
TI  - MR imaging of dysplasia epiphysealis hemimelica: bony and soft-tissue
      abnormalities.
AB  - OBJECTIVE: The purpose of this study is to describe the bony and, to our
      knowledge, previously unreported associated soft-tissue abnormalities seen on MR
      imaging of dysplasia epiphysealis hemimelica. CONCLUSION: MR imaging accurately
      depicted bony and cartilagenous structural abnormalities in multiple planes and
      revealed previously undescribed secondary changes in menisci, tendons, ligaments,
      and muscle. MR imaging is of value in the assessment of patients with this
      disorder.

PMID- 10063890
TI  - Abnormal three-vessel view on sonography: a clue to the diagnosis of congenital
      heart disease in the fetus.

PMID- 10063891
TI  - Subarachnoid contrast enhancement mimicking subarachnoid hemorrhage after
      coronary angiography.

PMID- 10063892
TI  - Rounded atelectasis and mesothelioma.

PMID- 10063893
TI  - Re: Gadolinium-enhanced MR angiography for carotid artery disease.

PMID- 10063894
TI  - Trojan horses and stereotactic breast biopsy.

PMID- 10063895
TI  - Scatter fraction and image contrast.

PMID- 10063896
TI  - Friday afternoon pulmonary arteriography.

PMID- 10063897
TI  - Lung emphysema: a softer filter for a smoother diagnosis.

PMID- 10063898
TI  - Multifocal hepatic steatosis in HIV infection.

PMID- 10063899
TI  - Pancreatic metastasis from hepatocellular carcinoma.

PMID- 10063900
TI  - Emphysematous pyelonephritis in a transplanted kidney: successful percutaneous
      treatment.

PMID- 10063901
TI  - Cervical radiculopathy due to epidural varicose veins.

PMID- 10063902
TI  - Thorotrast revisited: contrast-induced hepatic neoplasm.

PMID- 10063903
TI  - Pseudoaneurysm of aortic cannulation site after coronary artery bypass grafting:
      evaluation with gadolinium-enhanced MR angiography.

PMID- 10063904
TI  - Pulmonary artery aneurysms due to Behcet's disease: MR imaging and digital
      subtraction angiography findings.

PMID- 10063906
TI  - Helicobacter pylori water extract induces interleukin-8 production by gastric
      epithelial cells.
AB  - In Helicobacter pylori-associated gastric mucosal injury, interleukin (IL) -8, a
      potent leukocyte chemoattractant, is produced by epithelial cells infected by H.
      pylori and directs neutrophils to the gastric mucosa. According to previous
      studies, the IL-8 production requires direct contact between the bacteria and
      epithelial cells. The aims of the present study were to determine whether an H.
      pylori water extract (HPE) induces IL-8 production by gastric epithelial cells
      and to characterize IL-8-inducing substances in HPE. Extracts were prepared from
      a standard strain and from strains obtained from patients with gastric ulcers.
      After addition of HPE to MKN 45 cells, a gastric cancer cell line, IL-8 in
      supernatants and IL-8 mRNA were measured by immunoassay and reverse transcription
      polymerase chain reaction, respectively. For characterization, active fractions
      obtained by gel filtration of standard-strain HPE were treated by heating or
      trypsinization. To study the signal pathway leading to IL-8 production,
      inhibitors for protein kinase A (PKA), protein kinase C (PKC), or protein
      tyrosine kinase (PTK) were incubated with MKN45 cells before HPE stimulation. HPE
      from the standard strain and one of these clinical strains induced IL-8
      production. Lipopolysaccharide or cagA in the strains showed no correlation with
      IL-8 concentration. Standard-strain HPE induced IL-8 mRNA expression in MKN 45
      cells. Gel filtration localized activity to a low-molecular-weight fraction of
      about 7 kDa, which was resistant to heat and trypsin digestion. PKC inhibitors
      significantly blocked HPE-induced IL-8 production by MKN 45 cells; however, the
      PKA inhibitor or PTK inhibitors showed a partial inhibitory effect. HPE contains
      a nonprotein substance of low molecular weight that is responsible for IL-8
      induction in gastric epithelial cells. This induction is mainly dependent on the
      activation of PKC but partially also dependent on PKA or PTK.

PMID- 10063905
TI  - Extradigestive manifestations of Helicobacter pylori infection: fact and fiction.

PMID- 10063907
TI  - Relationship between persistence of Helicobacter pylori and dysplasia, intestinal
      metaplasia, atrophy, inflammation, and cell proliferation following partial
      gastrectomy.
AB  - Helicobacter pylori and partial gastric resection are risk factors for gastric
      cancer. Our aims were to investigate the presence of H. pylori in postgastrectomy
      patients and to correlate that with alterations in mucosal architecture and cell
      proliferation. One hundred fifty-one endoscopic biopsies from 22 patients, (15-47
      years of age, mean 29.2 years) following partial gastrectomy with Billroth II
      reconstruction for peptic ulcer disease, were examined for the presence of H.
      pylori using Giemsa staining. Sections were scored for grade of hyperplasia,
      intestinal metaplasia, dysplasia, inflammation, and atrophy. Immunohistochemistry
      for proliferative cell nuclear antigen (PCNA) was used to characterize cell
      proliferation. H. pylori was observed in 17/22 (77.3%) of patients or in 57/151
      (37.7%) of biopsies. Metaplasia was seen in 18/22, chronic atrophic gastritis in
      20/22, and cystic glandular dilation in 21/22 patients. The highest type of
      metaplasia in each patient was: four Type I, five Type IIA and nine Type IIB.
      Dysplasia was present in 16 biopsies from nine patients. H. pylori was more
      prevalent in intestinal metaplasia type I (44.8% of biopsies), than in type IIA
      (32.7%) or type IIB (25%). No H. pylori was detected in regions showing dysplasia
      or cystic glandular dilation. H. pylori colonization was associated with degree
      of inflammation (P = 0.00001) and cell proliferation (P = 0.0001). In conclusion,
      H. pylori is commonly seen many years after gastrectomy, it is associated with an
      increased epithelial cell proliferation, and it is not present in areas of
      histologic markers of premalignancy (type IIB metaplasia and dysplasia).

PMID- 10063908
TI  - Helicobacter pylori infection and atrophic gastritis: a nested case-control study
      in a rural town in Japan.
AB  - A seroepidemiologic, nested case-control study was conducted to evaluate the risk
      for atrophic gastritis associated with Helicobacter pylori infection. Atrophic
      gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I
      level < or = 70 ng/ml and pepsinogen I/pepsinogen II ratio < or = 3.0. Cases were
      23 men and 39 women who were not diagnosed with atrophic gastritis in 1987, but
      who were diagnosed with the condition in 1992. Controls were the 120 men and 282
      women who did not meet the serologic criteria for atrophic gastritis in either
      time period. Neither cases nor controls had a history of upper gastrointestinal
      operations. Helicobacter pylori infection at the initial survey was associated
      with a significantly increased risk of atrophic gastritis incidence for both
      sexes combined (odds ratio = 3.72; 95% confidence interval, 1.78-7.79; P =
      0.0005). Cigarette smoking and consumption of alcohol and green-yellow vegetables
      were not associated with incidence of atrophic gastritis.

PMID- 10063909
TI  - Healing of Helicobacter pylori-induced gastric ulcers in Mongolian gerbils:
      combined treatment with omeprazole and clarithromycin.
AB  - Helicobacter pylori can colonize the stomachs of Mongolian gerbils and
      subsequently induce penetrating ulcers five months later. Using this gerbil
      model, the effects of both combined treatment with omeprazole and clarithromycin,
      as well as treatment with each drug separately, on the healing of H. pylori
      induced gastric ulcers, and the effects of the cessation of the drug treatment on
      healed ulcers were examined. Beginning five months after H. pylori (NCTC11637)
      inoculation, omeprazole (four weeks), clarithromycin (two weeks), their
      combination, or the vehicle was orally administered once daily. These drugs, in
      combination or separately, markedly enhanced ulcer healing and lowered the
      increased myeloperoxidase (MPO) activity. While omeprazole had no effect on
      viable H. pylori, clarithromycin and the drug combination significantly reduced
      viable H. pylori. The degree of bacterial eradication was much higher in the case
      of the drug combination compared to clarithromycin alone. Four months after
      cessation of the treatment, visible ulcers, hypertrophic gastritis and increased
      MPO activity were found in the control animals (all H. pylori-positive).
      Nonetheless, only one of the eight gerbils subjected to the drug combination
      developed a small ulcer, although no hypertrophic gastritis was exhibited. It is
      concluded that: (1) the gerbil model of H. pylori infection is useful for the
      study of ulcer healing; (2) combined treatment with omeprazole and clarithromycin
      enhances the ulcer healing in infected gerbils; and (3) healed ulcers do not
      relapse, despite cessation of the drug treatment.

PMID- 10063910
TI  - Redox regulation of interleukin-8 expression in MKN28 cells.
AB  - Recent evidence suggests a role of reactive oxygen intermediates (ROI) in
      intracellular signaling and regulation of gene expression. We examined whether
      expression of interleukin-8 (IL-8), a key cytokine in the inflammatory responses
      of gastric epithelial cells, is sensitive to antioxidants and oxidative stress.
      IL-8 secretion was quantified by IL-8 enzyme-linked immunosorbent assay, and IL-8
      mRNA expression was determined by northern blot analysis. Electrophoretic
      mobility shift assay was performed to detect the transcription factor, nuclear
      factor kappaB (NF-kappaB). N-Acetylcysteine (NAC) or dimethylsulfoxide inhibited
      IL-8 expression induced by tumor necrosis factor-alpha (TNF-alpha) or interleukin
      1beta (IL-1beta). Externally applied H2O2 significantly up-regulated IL-8
      expression. TNF-alpha-induced activation of NF-kappaB activity was suppressed by
      NAC, and H2O2 caused significant activation of NF-kappaB. Since ROI production is
      increased in the inflamed gastric mucosa, for example, in H. pylori-associated
      gastritis, the present results suggest that ROI may be an important modulator of
      IL-8 expression in gastric mucosal cells.

PMID- 10063911
TI  - Subclinical esophageal peristaltic dysfunction during the early phase following a
      stroke.
AB  - Evaluation of swallowing following stroke has previously concentrated on the
      oropharyngeal phase. We have studied whether there is esophageal dysmotility
      during the early phase following stroke in patients with no clinical evidence of
      oropharyngeal dysfunction. Twenty-five patients with a clinical diagnosis of
      stroke, and CT scan confirmation, without swallowing abnormalities at bedside
      evaluation were studied. Each subject had two esophageal manometric studies, one
      between days 3-5 after the stroke and the second during the third week after the
      stroke. Mean percentage (+/-SE) of completed peristaltic events increased from
      57.8 +/- 5.9 (days 3-5) to 77.3 +/- 3.9 (week 3) (P = 0.005). Mean propagation of
      peristalsis (+/-SE) between 10 and 5 cm above the lower esophageal sphincter
      increased from 2.9 +/- 0.2 cm/sec (days 3-5) to 3.7 +/- 0.3 cm/sec (week 3) (P =
      0.003). We have demonstrated subclinical peristaltic dysfunction in the smooth
      muscle segment of the esophagus in stroke patients with relatively preserved
      oropharyngeal function.

PMID- 10063912
TI  - Effects of hyperglycemia on cortical response to esophageal distension in normal
      subjects.
AB  - Acute changes in the blood glucose concentration affect the intensity of
      gastrointestinal sensations. The aim of this study was to examine the effects of
      hyperglycemia on cortical potentials evoked by esophageal distension. In 16
      healthy volunteers, a balloon was positioned in the lower esophagus. A series of
      50 distensions was performed at both a lower volume (producing definite
      sensation) and a higher volume (producing unpleasant sensation), at blood glucose
      concentrations of 5 and 13 mmol/liter. Triphasic cortical potentials were
      recorded from a midline scalp electrode (Cz). During euglycemia, interpeak
      amplitudes were greater at the higher than the lower balloon volume (P < 0.005).
      At the lower balloon volume, the interpeak amplitudes were greater during
      hyperglycemia than euglycemia (P < 0.05). There was no effect of the blood
      glucose concentration on amplitude at the higher balloon volume. We conclude that
      in healthy subjects, the amplitude of the cortical response to moderate, but not
      unpleasant, esophageal distension is greater during hyperglycemia when compared
      to euglycemia. These observations are consistent with the concept of increased
      intensity of gut sensation during hyperglycemia.

PMID- 10063913
TI  - Evaluation of effects of ethyl alcohol and bismuth subsalicylate on gastric
      mucosal barrier in man.
AB  - The mucus-bicarbonate barrier provides the first line of defense against
      potentially harmful gastric luminal contents. Its integrity can be assessed in
      man by demonstrating the presence of a pH gradient across the mucus gel layer,
      from the acidified lumen to near-neutral pH at the mucosa. Our aim was, firstly,
      to assess the effects of ethyl alcohol and bismuth subsalicylate on the integrity
      of this lumen-to-mucosal pH gradient and, secondly, to evaluate whether
      pretreatment with bismuth subsalicylate would protect against any deleterious
      effects of ethyl alcohol. Ten healthy adults underwent two upper endoscopic
      procedures with microelectrode measurement of juxtamucosal pH gradients. At the
      first endoscopy, the effects of 30 ml of bismuth subsalicylate on the gradient
      was evaluated. At the second endoscopy, gradients were measured before and after
      luminal installation of 60 ml of ethyl alcohol (40% v/v) and following
      pretreatment with either 30 ml of bismuth subsalicylate or placebo. pH
      measurements were technically easy to perform and provided consistently
      reproducible results. A distinct juxtamucosal pH gradient (pH 4.0 +/- 0.2 units)
      was identified in all subjects in the basal state. Neither bismuth subsalicylate
      nor ethyl alcohol had a significant effect on these gradients. We conclude that a
      distinct pH gradient between gastric luminal fluid and the mucus gel layer can be
      readily demonstrated in man. Neither bismuth subsalicylate nor ethyl alcohol have
      a significant effect on this gradient.

PMID- 10063914
TI  - Esophageal exposure to ethanol increases risk of acid damage in rabbit esophagus.
AB  - Heavy alcohol consumption is associated with the development of reflux
      esophagitis. Among the reasons for this are impairment of the antireflux barrier,
      stimulation of acid secretion, and altered tissue resistance. To explore the
      contribution of altered tissue resistance to the development of esophagitis,
      sections of rabbit esophageal epithelium were mounted in Ussing chambers and
      exposed luminally to 10% ethanol, acid (HCl, pH 2), or combinations of both.
      Tissue injury was assessed by measurements of potential difference (PD), short
      circuit current (Isc) and electrical resistance (R) and by histology. Tissues
      exposed luminally to HCl for 1 hr exhibited little or no change electrically or
      morphologically compared to Ringer controls, while luminal exposure to 10%
      ethanol for 1 hr lowered PD (53 +/- 4%), Isc (30 +/- 1%), and R (31 +/- 5%) and
      produced cellular edema in the upper layers. Simultaneous exposure to ethanol and
      acid resulted in significantly greater declines in PD (81 +/- 1%) and Isc (70 +/-
      2%), but not R (40 +/- 4%), and greater morphologic damage. Moreover, this
      vulnerability of ethanol-exposed tissues to acid was demonstrable at generally
      innocuous levels of acidity (pH 2-4), after only short periods of ethanol
      exposure (10 min) and with delays for acid exposures of up to 1 hr following
      ethanol removal from the bathing solution. In conclusion, ethanol has a direct
      noxious effect on esophageal epithelium, which predisposes the tissue to acid
      injury. Tissue vulnerability develops with even short exposures to clinically
      relevant concentrations of ethanol, lasts for at least 1 hr after ethanol
      clearance, and transforms relatively innocuous concentrations of acid into
      damaging agents. These results support the likelihood that ethanol's ability to
      alter tissue resistance plays an important role in the development of reflux
      esophagitis in humans.

PMID- 10063915
TI  - Duodenoesophageal reflux induces apoptosis in rat esophageal epithelium.
AB  - The esophageal epithelial damage caused by duodenoesophageal reflux was examined
      by assessing histology, free radicals, and apoptosis in rats with an end-to-side
      esophagoduodenostomy (reflux group) or sham operation. Rats were sacrificed at 1,
      6, or 12 weeks after surgery. Reflux-associated hyperplasia was noted in the
      reflux group at 6 and 12 weeks. The reflux group manifested glutathione (GSH)
      overproduction at one and six weeks. Apoptotic cells were detected by the
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling
      method. Significantly increased numbers of apoptotic cells were seen on the
      epithelial surface in the reflux group at 6 and 12 weeks. Duodenoesophageal
      reflux causes esophageal injury with hyperplasia. Early GSH overproduction
      indicated that reflux esophagitis may be partly mediated by free radicals.
      Increased apoptosis may counteract increased proliferation and may be a
      protective mechanism against increased genotoxic events.

PMID- 10063916
TI  - Upper gastrointestinal ulceration with alendronate.

PMID- 10063917
TI  - Reliability block diagrams to model the management of colorectal cancer.
AB  - The present study aims to show how various medical and nonmedical components
      contribute to success and failure in the management of colorectal cancer. The
      first encounter, subsequent diagnosis, and surgical therapy of a patient with
      Dukes B sigmoid cancer is modeled as a reliability block diagram with a serial
      and parallel arrangement of various components. The overall probability of a
      patient with new-onset colorectal cancer to visit a physician, be correctly
      diagnosed, and undergo successful therapy is 69%. The reduction in the overall
      success, despite the fact that the majority of components are assumed to function
      with failure rates of 5% or less, is a reflection of the multitude of serial
      subsystems involved in the management of the patient. In contrast, the parallel
      arrangement of subsystems results in a relative insensitivity of the overall
      system to failure, a greater stability, and an improved performance. Since no
      medical system functions perfectly, redundancy associated with parallel
      subsystems assures a better overall outcome. System analysis of health care
      provides a means to improve its performance.

PMID- 10063918
TI  - Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by
      intraluminal peptones in rat.
AB  - The aim of this study was to determine the mechanisms implicated in the
      gastrointestinal inhibition induced by ovoalbumin hydrolysate infused
      intraluminally. We studied the site of action, the possible implication of GLP-1,
      and the nervous mechanisms involved. We prepared anesthetized Sprague-Dawley rats
      with strain gauges in the antrum, duodenum, and proximal jejunum and a catheter
      in the duodenum or ileum for peptone infusion. Both intraduodenal (N = 6) and
      intraileal (N = 5) infusion of ovoalbumin hydrolysate induced inhibition of
      spontaneous motor activity in the antrum, duodenum, and proximal jejunum.
      Duodenal inhibition induced by intraduodenal (N = 6) or intraileal (N = 6)
      infusion of ovoalbumin hydrolysate was reversed by intraarterial infusion of GLP
      1 receptor antagonist, exendin (9-39) (3 x 10(-8) mol/kg/40 min). Finally, a
      combination of the adrenergic blockers phentolamine and propranolol (1 mg/kg,
      each; N = 7) completely blocked inhibitory gastrointestinal motor actions caused
      by intraduodenal infusion of ovoalbumin hydrolysate. This study demonstrates that
      peptone, intraluminally infused, participates in the regulation of
      gastrointestinal motility through stimulation of adrenergic pathways in
      anaesthetized rats. Moreover, these effects are partly mediated by GLP-1
      secretion. The ileum seems to be the site of action, indicating a role of GLP-1
      on the ileal break mechanism.

PMID- 10063919
TI  - Fat intolerance depends on rapid gastric emptying.
AB  - Patients with fat intolerance complain of early satiety, bloating, nausea, and
      vomiting. Since these symptoms are similar to those of patients with
      postgastrectomy dumping syndrome, we hypothesized that fat intolerance may be
      associated with early, rapid gastric emptying. Using a three-meal gastric
      emptying study, we compared gastric emptying in nine patients with a history of
      fat intolerance and nine normal volunteers. On three separate days, 500-ml
      radiolabeled test meals containing 0, 15, or 60 g of fat were studied. The
      percentages of the test meal emptied at 15 and 60 min were analyzed by repeated
      measures two-way ANOVA. At 15 min (p < 0.05) but not 60 min, gastric emptying was
      faster in patients than normals. Gastric emptying at 15 min (p < 0.001) and 60
      min (p < 0.001) depended on the dose of fat. We conclude that fat intolerance is
      associated with early, rapid gastric emptying.

PMID- 10063920
TI  - Comparison of ultrasound-secretin test and sphincter of Oddi manometry in
      patients with recurrent acute pancreatitis.
AB  - Manometry is considered the gold standard for evaluating sphincter of Oddi
      dysfunction. It has recently been demonstrated that the ultrasound (US) secretin
      test proposed a few years ago as a noninvasive test for the study of sphincter of
      Oddi dysfunction yields a substantial percentage of pathological findings in
      patients with acute recurrent pancreatitis. The aim of this study was to compare
      the results of the US secretin test with sphincter of Oddi manometry findings in
      a consecutive series of patients with recurrent acute pancreatitis. Forty-seven
      patients admitted to our gastrointestinal unit suffering from recurrent acute
      pancreatitis underwent ultrasonographic measurement of the main pancreatic duct
      at baseline and for 60 min after maximal stimulation with secretin at 1 IU/kg.
      According to the US secretin test findings in 35 healthy control subjects, the
      test results were considered to indicate pathology when the duct was still
      dilated after 20 min. Within three to seven days the same patients underwent
      perendoscopic manometry. Thirty-six patients (17 men, 19 women; mean age 41 +/-
      15 years) had a successful US secretin test and sphincter of Oddi manometry.
      Eleven patients (30.6%) presented normal manometric findings. Two of these had an
      abnormal US secretin test. Twenty-five patients had abnormal manometry findings,
      revealing stenosis in 19 (52.7%) (17 with abnormal US secretin test) and
      dyskinesia in six (five with an abnormal US secretin test). Compared to manometry
      findings, the US secretin test sensitivity and specificity for sphincter of Oddi
      dysfunction were 88% and 82%, respectively. In conclusion, most patients with
      recurrent acute pancreatitis have sphincter of Oddi dysfunction documented by
      both at the US secretin test and sphincter of Oddi manometry; results of the US
      secretin test are reliable compared to sphincter of Oddi manometry, and therefore
      the US secretin test may offer a valid alternative to the more expensive and
      invasive manometric procedure for assessing sphincter of Oddi dysfunction in
      patients with recurrent acute pancreatitis.

PMID- 10063921
TI  - Novel carboxamide derivative (IS-741) attenuates lung injury in rats with
      cerulein-induced pancreatitis complicated by endotoxemia.
AB  - The therapeutic effects of an intravenously injected carboxamide derivative (IS
      741) on lung injury were studied in rats with cerulein-induced pancreatitis
      complicated by endotoxemia. Pancreatitis was induced by four intramuscular
      injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were
      injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 hr
      following the first cerulein injection as a challenge of endotoxemia. Rats were
      divided into four groups: group I, pancreatitis with LPS; group II, pancreatitis
      with LPS treated with a continuous intravenous injection of IS-741 at 0.03
      mg/kg/hr); group III, pancreatitis with LPS treated with a continuous intravenous
      injection of IS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis with LPS treated
      with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 was
      administered 30 min before the endotoxemia challenge. Intense mononuclear cell
      infiltration and lung hemorrhage occurred in untreated pancreatitis rats with LPS
      (group I), but hemorrhage was not seen in group IV rats receiving a continuous
      injection of IS-741 shortly before the induction of endotoxemia. The IS-741
      treated rats (groups II, III, and IV) had lower serum concentrations of cytokine
      induced neutrophil chemoattractant (CINC), as well as fewer pulmonary infiltrates
      immunoreactive for CINC or Mac-1 (CD11b/CD18). The number of neutrophils
      infiltrating the lung in groups II, III, and IV was significantly lower than that
      of group I. Conversely, CINC production by bronchoalveolar macrophages in vitro
      were stimulated by LPS but were reduced by the presence of IS-741. The
      carboxamide derivative IS-741 effectively prevented pancreatitis-associated lung
      injury following the challenge of endotoxemia.

PMID- 10063922
TI  - Serum pancreatic enzyme concentrations in chronic viral liver diseases.
AB  - Serum amylase and lipase concentrations were determined in 78 patients with
      chronic liver diseases [26 chronic active hepatitis (CAH) and 52 liver cirrhosis]
      and in 15 healthy subjects. Pancreatic isoamylase concentrations and macroamylase
      complexes were assayed in hyperamylasemic sera. Serum amylase levels were
      abnormally elevated in 27 patients (35%; 22 liver cirrhosis, 5 CAH), whereas
      serum lipase levels were elevated in 16 patients (21%; 15 liver cirrhosis, 1
      CAH). In 9 of the 27 hyperamylasemic patients, the hyperamylasemia was of
      pancreatic type. Macroamylasemic complexes were not detected in hyperamylasemic
      sera. Patients with liver cirrhosis had serum levels of amylase and lipase
      significantly higher than both the healthy subjects and the patients with CAH,
      while no significant differences were found in serum levels of these enzymes in
      patients with CAH as compared to the healthy subjects. A decreased liver
      metabolism of serum amylase and lipase in patients with chronic infective liver
      disease, especially in those having liver cirrhosis, may lead to an accumulation
      of these enzymes in the blood.

PMID- 10063923
TI  - Role of endothelin in obstructive jaundice.
AB  - Mediators responsible for renal changes in obstructive jaundice are not
      specified. This study is designed to study the role of endothelin-1 (ET-1) in
      obstructive jaundice in rats. Animals were randomly placed into five experimental
      groups. Group 1 (N = 3) was the sham-operated group. Group 2 (N = 8) after common
      bile duct (CBD) ligation, received bosentan, which is a nonselective endothelin
      receptor blocker, 50 mg/kg/day for seven days. Group 3 (N = 7) received 1
      microg/kg/day captopril. Group 4 (N = 7) was given both drugs orally for seven
      days. Group 5 (N = 6) after CBD ligation, received Arabic gum as the vehicle.
      Blood was drawn from the infrahepatic vena cava for the determination of ET-1,
      bilirubin, creatinine, protein oxidation products, hyaluronic acid, and beta-N
      acetyl-hexosaminase. Liver tissue samples were obtained to determine glutathione
      levels. ET-1, protein oxidation products, hyaluronic acid, bilirubin, and
      creatinine levels increased significantly in the control group when compared with
      sham. Bosentan effectively prevented ET-1 elevation but could not reverse
      creatinine or bilirubin elevation. Captopril with or without bosentan was
      cytoprotective but did not reverse increased creatinine levels. It is concluded
      that increased ET-1 in obstructive jaundice may be one of the contributing
      factors of renal damage.

PMID- 10063924
TI  - Expansion conditions for early hepatic progenitor cells from embryonal and
      neonatal rat livers.
AB  - Long-term primary cultures were established from fetal or neonatal livers by
      using cell suspensions depleted of red blood cells and by culturing the cells in
      hormonally defined medium containing dimethyl sulfoxide. Two distinct populations
      of hepatic progenitor cells were evident in the cultures, based on morphology,
      proliferative ability, and liver-specific gene expression. Most colonies
      consisted of immature hepatic progenitors: small, blastlike cells, weakly
      expressing alpha-fetoprotein, albumin, and gamma-glutamyltranspeptidase, and
      showing evidence of proliferation as measured by bromodeoxyuridine incorporation.
      At the perimeter of these colonies of immature cells and forming some colonies by
      themselves were more mature hepatic progenitor cells: larger cells, with
      increased cytoplasmic to nuclear ratios, little proliferation, and strongly
      expressing albumin, alpha-fetoprotein, and gamma-glutamyltranspeptidase. The
      latter two proteins were localized to the bile canalicular membranes of these
      cells. Glycogen deposits were present in the mature cells from day 14 embryos
      after eight days of culture. Thus, DMSO treatment of hepatic parenchymal
      progenitors provides a novel system for studies of liver development.

PMID- 10063925
TI  - Adrenomedullin, a vasodilator peptide implicated in hemodynamic alterations of
      liver cirrhosis: relationship to nitric oxide.
AB  - This prospective cohort study was aimed at investigating the role of
      adrenomedullin, a potent vasodilator peptide, in liver cirrhosis and its
      relationship with nitric oxide and cytokines. Overall, 66 consecutive patients
      with liver cirrhosis and 15 controls matched for age and sex distribution were
      included. Adrenomedullin levels in patients with cirrhosis were higher than in
      controls [28.1 (23.5-34.8) vs 21.9 (21.1-26.4) pmol/liter, P = 0.002]. Child
      class A patients had adrenomedullin levels similar to those of controls, but
      lower than patients in class B and C, respectively (P = 0.01). Patients with
      ascites showed more elevated adrenomedullin levels than patients without (P =
      0.001). Adrenomedullin levels had significant correlations with aldosterone (r =
      0.55; P < 0.001), plasma renin activity (r = 0.49; P < 0.001) and nitrates
      nitrites levels (r = 0.52; P < 0.001). Weak correlations were found with tumor
      necrosis factor-alpha and interleukin-6. This study shows that high levels of
      adrenomedullin in liver cirrhosis correlate with features associated with plasma
      volume expansion, and suggests that, in late stages of cirrhosis, adrenomedullin
      might contribute to vasodilatation by increasing the generation of nitric oxide.

PMID- 10063926
TI  - Prostaglandin E1 infusion and functional hepatic flow in control subjects and in
      patients with cirrhosis.
AB  - Metabolic effects of prostaglandin E1 have been previously demonstrated in
      cirrhosis, apparently independent of changes in large splanchnic vessel
      hemodynamics. The effects of prostaglandin E1 on functional liver blood flow were
      tested by measuring the extrarenal clearance of D-sorbitol in six controls and
      eight patients with cirrhosis during systemic superinfusion of saline or
      prostaglandin E1 (30 microg/hr), in random order. Doppler ultrasonography of
      systemic and splanchnic circulation was also performed before the test and at the
      end of the two study periods. Prostaglandin E1 infusion increased femoral blood
      flow by nearly 60% in controls and over 30% in cirrhosis, without any effect on
      mean arterial pressure and heart rate. Mesenteric artery and portal blood flow
      were unchanged, as were Doppler-measured resistance indices in the liver, spleen
      and kidney. Sorbitol-assessed functional hepatic flow was 30% lower in cirrhosis,
      and did not change systematically during prostaglandin E1 infusion. We conclude
      that prostaglandin E1, at doses able to elicit metabolic effects and changes in
      systemic hemodynamics, does not affect splanchnic blood flow and/or hepatic
      microcirculation in normal subjects and in portal-hypertensive patients with
      cirrhosis.

PMID- 10063927
TI  - Isolated polycystic liver disease not linked to polycystic kidney disease 1 and
      2.
AB  - Autosomal dominant polycystic liver disease occurs commonly in association with
      autosomal dominant polycystic kidney disease, types 1 and 2. It may also exist as
      a separate entity, genetically distinct from autosomal dominant polycystic kidney
      disease types 1 and 2, as has been recently established to exist in a Belgian
      family. We report here a large Argentinian family of Spanish-Belgian ancestry
      with autosomal dominant polycystic liver disease, where proximal and distal
      markers for both polycystic kidney disease 1 and 2 failed to demonstrate genetic
      linkage. The data support the notion that polycystic liver disease and autosomal
      dominant polycystic kidney disease may have separate chromosomal loci.

PMID- 10063928
TI  - Polycystic liver disease: an unusual cause of bleeding varices.

PMID- 10063929
TI  - Irradiation induces marked immunohistochemical expression of vasoactive
      intestinal peptide in colonic mucosa of man.
AB  - Vasoactive intestinal peptide (VIP) is known to modulate inflammatory reactions,
      to have trophic effects, and to contribute to diarrhea and has been implicated as
      an important factor in several inflammatory conditions in the human gut. The aim
      of the present study was to investigate the effects of irradiation on the
      expression of VIP in the colon of patients operated on for adenocarcinoma. Some
      of the patients had received preoperative irradiation (25 Gy) within one week
      before the operation. Specimens of sigmoideum, 10 cm cranial to the margin of the
      cancer, were examined, by using antiserum against VIP and immunohistochemistry.
      There were numerous nerve fibers showing VIP-like immunoreactivity in the damaged
      mucosa, including the regions showing ulcerations. There was a higher degree of
      expression of VIP in the ganglion cells in the submucous plexuses in irradiated
      than nonirradiated patients. The study shows that there is a marked
      immunohistochemical expression of VIP concomitant with the occurrence of
      inflammatory and repair processes in the irradiation-damaged human colonic
      mucosa.

PMID- 10063930
TI  - Measurement of small intestinal permeability markers, lactulose, and mannitol in
      serum: results in celiac disease.
AB  - To date, tests of small intestinal passive permeability have involved the
      ingestion of test molecules whose permeation is assessed indirectly by measuring
      their urinary recovery. Excretion ratios of marker molecules (eg, lactulose-to
      mannitol excretion ratio, LMER) are useful clinically. Measurement of
      permeability markers in serum would improve the convenience of the tests. Our aim
      was to assess small intestinal permeability in celiac patients using serum
      lactulose and mannitol levels with calculation of lactulose to mannitol serum
      ratios (LMSR) and to compare the results with the standard methods using urinary
      recoveries. Twenty-four newly diagnosed celiacs and 10 control subjects were
      studied; 10 celiacs were restudied while established on a gluten-free diet. Test
      subjects and patients ingested 10 g lactulose and 2.5 g mannitol in 50 ml water.
      In 10 untreated celiacs and the controls, blood was taken from 0 to 120 min and
      all urine was collected for 6 hr. The remaining 14 untreated and the 10 treated
      celiacs had a single serum sample taken 60 min after ingestion of the test
      solution. At 1 hr after ingestion, the mean mannitol level in normals (0.156
      mmol/liter) was significantly higher than in untreated celiacs (0.06 mmol/liter).
      The 1-hr mean serum lactulose level in normals (0.125 micromol/liter) was
      significantly lower than in untreated celiacs (0.56 micromol/liter). The median 1
      hr LMSR in untreated celiacs was 0.42 compared with 0.039 in normals and 0.08 in
      treated celiacs. There was a significant correlation between LMSR and LMER.
      Permeability testing using serum measurements of lactulose and mannitol gave
      comparable results in celiac patients to the tests using urinary recovery of the
      permeability markers and may prove to be more convenient, especially in pediatric
      patients.

PMID- 10063931
TI  - Small intestinal Na+,K+-adenosine triphosphatase activity and gene expression in
      experimental diabetes mellitus.
AB  - The Na+,K+-ATPase plays a key role in the absorption of electrolytes, water, and
      nutrients from the small intestine. The effect of streptozotocin-induced diabetes
      mellitus (STZ-DM) on the activity and expression of Na+,K+-ATPase in the rat
      small intestine was examined in the present study. Diabetes mellitus was induced
      by a single intraperitoneal injection of STZ (75 mg/kg) and control and STZ-DM
      rats were killed at day 30 (chronic diabetic state). Levels of Na+,K+-ATPase
      activity and numbers of sodium pumps were increased two- to threefold in the
      jejunum and ileum. Sodium pump kinetics were unaltered in STZ-DM. The levels of
      Na+,K+-ATPase alpha1 and beta1 isoform protein, corresponding mRNAs, and levels
      of transcription were increased in the jejunal and ileal mucosa of the
      chronically diabetic rat. The increases in Na+,K+-ATPase functional activity,
      protein expression, and mRNA were most marked at the level of the ileal mucosa.
      While a proximal to distal gradient in Na+,K+-ATPase activity and subunit isoform
      protein levels were observed in both control and diabetic rats, levels of subunit
      isoform mRNA abundance were similar in both regions of the small intestine in
      both groups of rats. The alterations in small intestinal Na+,K+-ATPase expression
      in the chronic diabetic state appear to involve alterations in transcriptional
      and posttranscriptional events and may likely represent an adaptive response that
      leads to increased Na+-coupled monosaccharide absorption in the context of a
      perceived state of nutrient depletion.

PMID- 10063932
TI  - Autoantibodies to molecular targets in neutrophils in patients with ulcerative
      colitis.
AB  - Autoantibodies against neutrophil granulocytes are frequently observed in
      patients with ulcerative colitis, but a precise description of the autoantigens
      involved is lacking. Therefore, sera from 75 patients with ulcerative colitis
      were studied for antibody specificities by means of indirect immunofluorescence
      microscopy, enzyme-linked immunosorbent assays, and immunoblotting of extracts of
      neutrophils, neutrophil granules and lymphocytes. Fifty-six percent of the sera
      reacted in indirect immunofluorescence with ethanol-fixed neutrophils. On
      formalin-fixed cells most sera shifted fluorescence pattern, indicating a
      cytoplasmic origin of antigen(s). Only a few sera reacted with specific, known
      antigens. Immunoblots showed reactions with a broad panel of antigens with
      preferences for proteins around 55-65 kDa, which were present in azurophilic
      granules and in cytosol, an 80-kDa protein found in the specific granules, and a
      110-kDa unknown cytosol component. In conclusion, neutrophil-specific IgG
      autoantibodies from ulcerative colitis patients react with several different
      antigens, most of which are of nonnuclear origin.

PMID- 10063933
TI  - Elevated serum vascular endothelial growth factor in children and young adults
      with Crohn's disease.
AB  - Vascular endothelial growth factor (VEGF) is a cytokine released by fibroblasts,
      epithelial cells, and leukocytes that potentiates vascular permeability and
      growth of new capillaries. Because of these multiple effects, VEGF has been
      postulated to play a role in the pathogenesis of autoimmune disease, as well as
      in wound healing. We hypothesized that VEGF was potentially important in
      mediating the vascular permeability and angiogenesis seen in Crohn's disease, and
      therefore that VEGF would be increased in the serum of children with Crohn's
      disease. Serum was obtained from 73 children and young adults with Crohn's
      disease, 47 with ulcerative colitis, and 29 controls. VEGF levels were measured
      by enzyme-linked immunosorbent assay. Mean VEGF levels were significantly higher
      in patients with Crohn's disease (436.4 +/- 37.2 pg/ml) than in ulcerative
      colitis (306 +/- 41.1 pg/ml) or control (167.8 +/- 29.6 pg/ml) patients. Serum
      VEGF also correlated significantly with disease activity, being elevated in
      patients with moderate/severe Crohn's disease and ulcerative colitis. We conclude
      that serum VEGF is released by inflamed tissues in children with Crohn's disease.
      This multifunctional cytokine could promote inflammation by increasing vascular
      permeability or promote wound healing by mediating capillary growth.

PMID- 10063934
TI  - Temporal patterns of colonic blood flow and tissue damage in an animal model of
      colitis.
AB  - This study tested the hypothesis that altered colonic blood flow may contribute
      to tissue damage during the development of colitis in the rabbit. This was
      achieved by using radioactive microspheres to measure colonic blood flow at
      various times after colitis induction with trinitrobenzene sulfonic acid.
      Significant colonic damage occurred 6 hours post colitis induction and persisted
      throughout the 5 day study. Blood flow to the muscularis propria and
      mucosa/muscularis mucosae compartments increased significantly from 5 minutes
      until one hour post induction. At 6 and 12 hours post induction colonic blood
      flow returned to control levels before increasing again from 24 to 96 hours. This
      second increase in flow was, however, predominantly in the mucosa/muscularis
      mucosae compartment. Blood flow in the stomach and non-gastrointestinal tissues
      did not change significantly at any time. These data demonstrate that increased
      colonic blood flow may be disrupted in the early stages of colitis and that this
      coincides with the onset of significant damage. It is concluded that maintenance
      of elevated colonic blood flow throughout the development of colitis may help to
      ameliorate subsequent tissue injury.

PMID- 10063935
TI  - SR140333, a substance P receptor antagonist, influences morphological and motor
      changes in rat experimental colitis.
AB  - The etiology of inflammation, edema, and smooth muscle contraction characteristic
      of inflammatory bowel disease is not clearly understood. There is evidence that
      several neuropeptides, including substance P (SP), may play a role. In this study
      we evaluated the ability of a SP-antagonist (SR140333) to modify the course of
      experimental colitis induced in the rat by trinitrobenzene sulfonic acid (TNB).
      Colitis was induced in 24 rats using TNB applied by intrarectal enema. Twelve TNB
      treated rats received SR140333, 0.1 mg/kg intraperitoneally, 30 min before the
      administration of TNB and every 48 hr until death. Twelve rats receiving only
      intrarectal 0.9% saline served as controls. Rats of each group were killed after
      14 days. At day 14, the control group showed no signs of inflammation whereas the
      TNB-treated rats without SR140333 treatment exhibited a well-established colitis.
      The TNB-treated group had a higher level of inflammation, as seen histologically
      and by the significantly greater weight of colon strips, compared to the controls
      (0.30 +/- 0.09 g vs 0.13 +/- 0.03 g, P < 0.001) and to the SR140333-treated rats
      (0.30 +/- 0.09 g vs 0.14 +/- 0.05 g, P < 0.001). In addition, smooth muscle
      contractility was significantly reduced in the inflamed colons of TNB-treated
      rats when compared with the controls (carbachol: 42.7 +/- 20.3 vs 254.2 +/- 69.78
      mg/mm2; SP: 18.5 +/- 10.02 vs 89.45 +/- 23.17 mg/mm2; KCl: 11.4 +/- 2.2 vs 98.32
      +/- 33.57 mg/mm2, P < 0.01). However, SR140333-treated rats showed a recovery
      from inflammation and motor alterations caused by TNB (carbachol: 150.9 +/- 46.1
      mg/mm2, P < 0.01; SP: 32.5 +/- 9.4 mg/mm2, P < 0.05; KCl: 125.7 +/- 36.1 mg/mm2,
      P < 0.01). In conclusion, treatment with SP antagonist SR140333 reduces the
      severity of colitis and has beneficial effects on the concomitant alterations of
      contractility. Thus, the blockade of substance P may represent a possibility in
      the treatment of intestinal inflammation.

PMID- 10063936
TI  - Mouse colitis induced by Escherichia coli producing Yersinia enterocolitica 60
      kilodalton heat-shock protein: light and electron microscope study.
AB  - In patients with inflammatory bowel disease (IBD), including ulcerative colitis
      (UC), heat-shock protein (Hsp) 60 has been detected in serum and the intestinal
      tract. Our mouse colitis model was established using Escherichia coli transformed
      with Yersinia enterocolitica Hsp60 gene as an immunizing antigen, and examined
      light and electron microscopically as compared with lesions of UC. The large
      intestine of mice injected with Hsp60 antigen showed swollen goblet cells,
      glandular dilation, erosion, ulceration, and infiltration of inflammatory cells.
      The change like crypt abscesses was also found, and various phases of
      inflammation were observed simultaneously in individual mice. In addition, the
      reticulum fibers were absent ultrastructurally in the subepithelial reticular
      layer. Hyperplasia of the thymus was found in antigen-treated mice. These lesions
      were similar to those of UC. These results suggest that UC-like enteritis in mice
      was induced by using Hsp60, considered as one of the pathogens for UC.

PMID- 10063937
TI  - Colitis in chronic granulomatous disease resembling Crohn's disease: comparative
      analysis of CD68-positive cells between two disease entities.

PMID- 10063938
TI  - Symptomatic hypertrophic obstructive cardiomyopathy: the role of dual-chamber
      pacing.
AB  - BACKGROUND AND PURPOSE: The management of symptomatic patients with hypertrophic
      obstructive cardiomyopathy (HOCM) has traditionally consisted of beta blockers
      and calcium channel blockers. Surgical treatment has been employed for operable
      patients who became refractory to medical therapy. However, associated
      complications, mortality rate, and recurrence of functional limitations have
      shifted the focus toward alternative therapy modalities. Recently, permanent dual
      chamber (DDD) pacemaker has been introduced as an alternative treatment option.
      PATIENTS AND METHODS: This study comprises clinical, angiographic,
      echocardiographic, and electrophysiologic data obtained at a single center on 10
      symptomatic patients with HOCM who received a DDD pacemaker after medical therapy
      failed to relieve symptoms. Presenting symptoms were exertional dyspnea and chest
      pain (60%), syncope (20%), and presyncope (20%). These symptoms were documented
      for 8.9+/-7.1 years before pacemaker implantation. All patients were in New York
      Heart Association functional class III or IV before pacemaker therapy. RESULTS:
      Placement of a permanent DDD pacemaker decreased the left ventricular outflow
      tract gradient from 83+/-44 mm Hg (range: 35-180 mm Hg) to 47.1+/-25.3 mm Hg
      (range: 10-75 mm Hg) in these patients. Within 1 to 30 months, follow-up found
      that the functional status of eight out of the 10 patients had improved to New
      York Heart Association class 0 or I. CONCLUSION: In selected patients with
      symptomatic HOCM who fail to respond to medical therapy, DDD pacemaker may offer
      a nonsurgical alternative treatment option. Large-scale multicenter, prospective,
      randomized trials are needed to establish the role of this modality in the
      treatment of hypertrophic obstructive cardiomyopathy.

PMID- 10063939
TI  - Noninvasive measurement of cardiac output: two methods compared in patients with
      mitral regurgitation.
AB  - In search for the origin of the less reliable cardiac output (CO) estimations by
      means of electrical impedance cardiography (EIC), the authors hypothesized that
      cardiac valve pathology might be one of the reasons. Twenty-six patients were
      examined by means of echo Doppler (ED) and EIC. The cardiac valve status was
      obtained by means of echocardiography and color Doppler flow, while CO was
      obtained by means of both methods. Seventeen patients had no valve pathology
      (nVP) while nine patients had mild to moderate mitral regurgitation (MVR). The
      overall correlation between the calculation of CO by means of the two methods was
      good (r = 0.85, p < 0.001, mean difference and standard deviation: 0.20+/-0.74
      L/min), while there was no significant difference between the paired values.
      After division into an nVP and an MVR population, the results showed an even
      closer agreement between the CO values in the nVP population (r = 0.88, p <
      0.001, mean difference and standard deviation: 0.15+/-0.68 L/min). Furthermore,
      significant differences were found in the first derivative of the impedance
      (dZ/dt) signals of these groups. Although the agreement between ED and EIC was
      slightly lower in the MVR population, EIC reliably estimated CO, even in case of
      MVR. The impedance signal itself gave an indication for the existence of MVR.

PMID- 10063940
TI  - Immunoscintigraphy of venous thrombi: clinical effectiveness of a new antifibrin
      D-dimer monoclonal antibody.
AB  - Safety and thrombus imaging capabilities of the 99mTc-labeled form of a new
      F(ab')2 monoclonal antibody (MoAb) against fragment D dimers from cross-linked
      human fibrin, previously shown to be effective labeled to 131I in detecting
      venous thrombi in the rabbit, were investigated. Sixteen patients (seven men,
      mean age: 60+/-7 years) with deep (n = three) and superficial (n = 13) venous
      thromboses of the lower limbs documented at echo-Doppler study underwent, 24
      hours before saphenous vein stripping, a scintigraphic study after IV injection
      of the 99mTc-MoAb (1,129+/-275 MBq/mL), acquiring dynamic images, as well as
      early and delayed static images of lower limbs. Tracer activity was compared in
      normal and pathologic areas. At the operation, vessel wall including the
      thrombotic lesion was isolated, weighed, and counted. Blood radioactivity and
      MoAb concentration were also measured. No adverse reaction was observed after
      MoAb administration. Thrombus site appeared as a focal area (hot spot) of
      asymmetrically increased tracer uptake, already detectable at early images in all
      patients. All thrombi detected at echo-Doppler study (n=25) were confirmed at
      scintigraphic study, which showed four additional hot spots subsequently
      confirmed to represent thrombi at operation. Average percent ratio between
      pathologic and normal regions was 1.51+/-1.34 (p < 0.05) at time-activity curves,
      2.27+/-1.1 (p < 0.05) at early static images, and 2.15+/-1.2 (p < 0.05) at
      delayed images, respectively. Thrombus-to-blood uptake ratio was 4.3+/-0.9 (p <
      0.01). The F(ab')2 MoAb proved to be safe, and low levels of antimouse antibodies
      were detected in response, although further studies are needed to assess
      tolerance and effectiveness in case of a second administration in the same
      patient. The 99mTc-labeled MoAb was very effective in identifying venous
      thromboses both at deep and superficial localizations, although its sensitivity
      and specificity need be evaluated in a more numerous group, including also
      patients with different and clinically more relevant localizations, such as caval
      thromboses. However, the possibility of obtaining high-quality images within 4
      hours of MoAb administration is clinically relevant, and carries also therapeutic
      implications, especially in pulmonary thromboembolism.

PMID- 10063941
TI  - Doppler-based diagnosis of restenosis after femoropopliteal percutaneous
      transluminal angioplasty: sensitivity and specificity of the ankle/brachial
      pressure index versus changes in absolute pressure values.
AB  - The aim of this study was to investigate the sensitivity and specificity of
      changes of the ankle/brachial pressure index (ABI) and changes in absolute ankle
      pressure values to detect restenosis in patients who underwent femoropopliteal
      percutaneous transluminal angioplasty (PTA). In total, 171 patients were followed
      up prospectively for 12 months; sensitivity and specificity of Doppler-based
      diagnosis were calculated with duplex scanning as the gold standard. The criteria
      for restenosis were: (1) a loss of 50% of the ABI increase or (2) loss of 50% of
      the absolute ankle systolic pressure, gained by PTA. For both criteria, different
      cut-off points (minimum increase of ABI or ankle pressure gained by PTA) were
      evaluated. The overall sensitivity and specificity of the ABI criterion was 67%
      and 80%, respectively. The introduction of cut-off points (the minimum ABI
      increase gained by PTA), ranging between > or = 0.13 and > or = 0.35, did not
      markedly improve the results. The overall sensitivity and specificity of the
      absolute ankle pressure criterion again was poor (59% and 81%). With the
      introduction of cut-off points (the minimum increase of absolute ankle pressure
      gained by PTA) ranging between > or = 15 mm Hg and > or = 20 mm Hg, the
      sensitivity and specificity of the criterion improved to acceptable 92% and 96%,
      respectively. It is concluded, that in the long-term follow-up of PTA patients,
      the "loss of 50% ankle pressure" criterion will detect restenosis with reasonable
      accuracy in those patients, in whom an increase in systolic ankle pressure > or =
      20 mm Hg is warranted.

PMID- 10063942
TI  - A double-blind, placebo-controlled study of the effects of policosanol in
      patients with intermittent claudication.
AB  - This study was undertaken to evaluate the efficacy and tolerability of
      policosanol, a new cholesterol-lowering drug with concomitant antiplatelet
      effects, in patients with intermittent claudication. After a baseline period of 6
      weeks, 62 patients were randomized to receive, under double-blind conditions,
      either placebo (31 patients) or policosanol (31), 10 mg twice daily. Walking
      distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees) were
      assessed before and after 6 months of treatment. Both groups were similar at
      randomization. Policosanol increased significantly (p < 0.01) the initial
      claudication distance from 132.5+/-13.5 m (baseline) to 205.7+/-36.3 m (after
      therapy) and the absolute claudication distance (p<0.0001) from 229.5+/-22.0 m to
      365.4+/-46.9 m; meanwhile both variables remained unchanged in the placebo group
      (p<0.05). The reduction of lower limb symptoms showed a greater benefit in the
      policosanol group. There was no significant change in either group in the
      ankle/arm pressure ratio. The treatment was well tolerated. There were 10
      discontinuations (seven placebo, three policosanol) from the study. Six
      withdrawals occurred because of adverse events (AE); all were in placebo
      patients. There were five serious vascular AEs in the placebo group but none in
      the policosanol group (p<0.05). Overall, 12/31 (38.7%) placebo patients and 3/31
      (9.7%) policosanol patients experienced AEs after randomization, which showed a
      lesser incidence of AEs in the policosanol group (p<0.01). The present study
      demonstrates a beneficial effect of policosanol in patients with intermittent
      claudication.

PMID- 10063943
TI  - Relation of mass/volume ratio to ECG abnormalities and symptoms in children with
      aortic stenosis/insufficiency.
AB  - In this study, to determine whether symptoms and ECG abnormalities relate to left
      ventricular (LV) mass, volume, and mass/volume (M/V) ratio in children with
      aortic stenosis (AS) and/or insufficiency (AI), the authors examined 23 patients
      with echocardiography. LV volumes and mass were calculated with echocardiography.
      Also, the peak and mean gradients across the aortic valve and left ventricular
      meridional wall stress (ESWS) were determined by use of echo Doppler techniques.
      Fourteen patients (mean age 5.84+/-3.49 years) had AS alone. Of these, 14 had
      symptoms and seven had abnormal-appearing ECGs. Nine patients (mean age 6.91+/
      4.35 years) had AS/AI. Of these nine, four had symptoms and two had ECG
      abnormalities. The authors observed that the incidences of symptoms and ECG
      abnormalities were higher in the patients with AS than in those with AS/AI. There
      was no significant correlation between symptoms and ECG abnormalities with peak
      gradient, mean gradient, valve area, LV mass, volume, and mass/volume ratio in
      patients with AS/AI. However, significant correlation was found between symptoms
      and ECG abnormalities and ESWS in AS/AI patients. In conclusion, ECG
      abnormalities and symptoms do not always indicate the severity of AS and AS/AI.

PMID- 10063944
TI  - Isosorbide aerosol: an option for the treatment of hypertensive crises.
AB  - In this study the authors assessed the effectiveness and safety of isosorbide
      dinitrate aerosol administered through the oral mucosa in 30 adult patients who
      presented with a hypertensive crisis (mean arterial pressure > 130 mm Hg and
      evidence of target organ damage). The patients were given a first dose of 1.25 mg
      of aerosol when they were admitted to the hospital; a second dose was
      administered 15 minutes later if the mean arterial pressure had not decreased by
      > 15%. An electrocardiogram (ECG) was obtained for every patient immediately
      prior to and 30 minutes after administration of the medication. Nine patients
      (30%) had a good response with one dose, whereas 21 patients (70%) required a
      second dose. All 30 patients had a significant reduction of the arterial blood
      pressure (187+/-13 / 121+/-6.6 to 153+/-15.3 / 92.3+/-7.6 mm Hg; p<0.005) as well
      as of the mean arterial pressure (136.6+/-8 to 109.5+/-7 mm Hg; p<0.005) in a
      period of 30 minutes. No adverse effects, rebound hypertension, or severe
      hypotension were observed. These figures remained under control for 6 hours. Two
      of the patients had angina pectoris at admission and their ECG showed
      subepicardial ischemia, both of which disappeared with the medication. A second
      ECG appeared normal. A reduction of 14% in heart rate was obtained (95+/-15 to
      82+/-14 beats per minute; p<0.005). These observations suggest that isosorbide
      dinitrate aerosol is an effective and safe alternative for the treatment of
      patients with hypertensive crises.

PMID- 10063945
TI  - Lupus carditis: evaluation with technetium-99m MIBI myocardial SPECT and heart
      rate variability.
AB  - The objective of this paper was to investigate the incidence of myocardial
      perfusion defects in patients with systemic lupus erythematosus (SLE) associated
      with dysautonomic alterations. Twenty patients without any sign or symptoms of
      heart disease, selected from a larger population of patients with SLE, underwent
      technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography
      (SPECT), at rest and after dipyridamole infusion; they also underwent heart rate
      variability (HRV) examination by a 24 hour ambulatory electrocardiography,
      analyzing in the time domain the standard deviation of the R-R intervals average
      (SDNN) and the percentage of R-R adjacent intervals differing from each other
      more than 50 msec (pNN50); in the frequency domain the low (LF) and high
      frequencies (HF) were analyzed. Twenty healthy volunteers served as control group
      for heart rate variability. At MIBI-SPECT examination, the scan was found
      abnormal in 15 patients and normal in five: three patients demonstrated
      reversible defects in the anteroseptal region, four had irreversible defects in a
      region (two in the anteroseptal region and two in the lateral region), two had
      rest defects in two different regions (lateral and inferior, lateral and
      anteroseptal) that improved during dipyridamole scan, and six had both reversible
      and irreversible defects: four in a single segment (three anteroseptal and one
      lateral, and two in two different regions, particularly anteroseptal and lateral,
      lateral and inferior). All 20 patients showed significantly lower HRV parameters
      in comparison with the control group, except for pNN50, which indicates decreased
      physiologic periodic fluctuations of the autonomic nervous system. In six
      patients who underwent coronary angiography, the epicardial vessels were found
      completely normal. In view of the high incidence of myocardial hypoperfusion in
      patients with HRV alterations, the authors hypothesize that autonomic dysfunction
      may be associated with microvascular disease or metabolic alteration. They also
      believe that MIBI scintigraphy is a suitable technique in detecting myocardial
      damage in SLE patients free of clinical manifestation.

PMID- 10063946
TI  - Bilateral subclavian steal syndrome through different paths and from different
      sites--a case report.
AB  - Cases of cerebro-subclavian steal syndrome have been reported in the medical
      literature since 1960. This most often occurs on the left side because of the
      higher rate of involvement of the left subclavian artery in comparison to the
      other brachiocephalic branches of the aortic arch. With the use of the internal
      mammory artery as a conduit for coronary artery bypass, in the past three decades
      increasing numbers of coronary-subclavian steal in addition to the cerebro
      subclavian steal have been observed. The authors report a case of bilateral
      subclavian steal syndrome through both vertebral arteries, the right common
      carotid artery, and the left internal mammory artery, without significant signs
      and symptoms of cerebral ischemia or anginal pain.

PMID- 10063947
TI  - Fibromuscular dysplasia involving coronary arteries--a case report.
AB  - The authors report a young patient with fibromuscular dysplasia involving
      multivessels including coronary arteries. If young patients have chest pain on
      effort, fibromuscular dysplasia of coronary arteries must be considered. As
      fibromuscular dysplasia is a chronic progressive disease and some cases progress
      rapidly in a few months, careful follow-up and comprehensive medical management
      may be necessary in such patients.

PMID- 10063948
TI  - Developing venous gangrene in deep vein thrombosis: intraarterial low-dose burst
      therapy with urokinase--case reports.
AB  - Two patients with developing venous gangrene of the lower extremity and
      contraindications to systemic thrombolytic therapy are presented. Low-dose
      intraarterial burst therapy with urokinase provided rapid amelioration of
      symptoms and avoided amputation without any serious bleeding complications in
      both patients.

PMID- 10063949
TI  - Crack-cocaine-associated aortic dissection in early pregnancy--a case report.
AB  - Even though uncommon in pregnancy, aortic dissection is a potentially
      catastrophic vascular complication, occurring mainly in the late stages of
      pregnancy. Vascular events, including aortic dissection are recognized
      complications of crack-cocaine use. The authors report a case of aortic
      dissection in early pregnancy related to crack-cocaine use. They believe that the
      combined effects of pregnancy and crack cocaine on the vasculature create the
      requisite milieu potentiating such catastrophic events as aortic dissection. This
      paper reviews the possible underlying pathophysiologic mechanisms and the
      available diagnostic, therapeutic, and management options.

PMID- 10063950
TI  - An unusual vascular graft infection by Aspergillus--a case report and literature
      review.
AB  - Vascular graft infection due to Aspergillus is a rare event. Only 11 previous
      case reports have been documented. All of these infections were in the aortic
      position, and infrainguinal arterial prosthetic graft involvement has been
      uncommon. The usual clinical presentation was back pain. Fever and systemic
      complaints were usually present. An unusual case that began with bilateral groin
      pain is reported and a review of the clinical presentation and the management of
      the other cases described in the literature is presented.

PMID- 10063951
TI  - Anomalous left coronary artery arising from right sinus of valsalva could be a
      minor congenital anomaly--a case report and review of the literature.
AB  - Left coronary artery arising from the right sinus of Valsalva is a rare
      congenital coronary anomaly. This anomaly is either benign or serious, depending
      on the relation of the anomalous left coronary artery to the aorta and pulmonary
      artery. Potentially serious anomaly is associated with sudden cardiac death and
      warrants prophylactic coronary bypass surgery. A rare case of anomalous left
      coronary artery arising from the right sinus of Valsalva is reported, documented
      by coronary angiography; however, it took a safer course between the aorta and
      pulmonary artery. Prophylactic surgery was not performed, for this benign anomaly
      may not carry the same risk of sudden cardiac death.

PMID- 10063952
TI  - Comparison of risk profile and outcomes in patients undergoing surgical and
      catheter-based revascularization.
AB  - BACKGROUND: The effects of the randomized revascularization trials and improved
      strategies and techniques for coronary artery bypass graft (CABG) surgery and
      percutaneous transluminal catheter-based revascularization (PTCR) on current
      patient selection and clinical outcomes are unknown. METHODS: We evaluated a
      concurrent, contemporary (1995 to 1997), and consecutive group of patients
      undergoing CABG (n = 982) or PTCR (n = 939) in a single institution that
      participated in the Bypass Angioplasty Revascularization Investigation (BARI)
      trial. Results are presented as percent or mean +/- SD. Compared to PTCR,
      patients undergoing CABG were older (66.2+/-10.7 vs. 62.0+/-11.8 years, p<0.05)
      with a higher incidence of hypertension (73.3% vs. 52.4%, p<0.05), diabetes
      (32.5% vs. 23.1%, p<0.05), active smoking (67.8% vs. 27.2%, p<0.05), prior
      myocardial infarction (MI)(66.8% vs. 28.5%, p<0.05), peripheral vascular disease
      (19.8% vs. 7.7%, p<0.05), prior cerebrovascular accident (CVA)/transient ischemic
      attack (TIA) (6.4% vs. 2.8%, p<0.05), and a lower ejection fraction (48.7%+/
      14.5% vs. 55.3%+/-11.7%, p<0.05). The presenting functional class and incidence
      of female gender were similar for both revascularization strategies. RESULTS:
      Compared to patients undergoing CABG, those undergoing PTCR were more likely to
      have single or two vessel coronary artery disease (88.6% vs. 23.1%, p<0.001) and
      had fewer vessels revascularized per patient (1.08+/-0.30 vs. 3.5+/-0.98,
      p<0.001). Outcomes were comparable for CABG and PTCR with a similar incidence of
      death (1.0% vs. 0.9%, NS), renal insufficiency (0.7% vs. 0.6%, NS), and CVA/TIA
      (0.9% vs. 0.3%, NS). Patients undergoing CABG had a higher incidence of pulmonary
      complications (5.2% vs. 1.0%, p<0.05), a lower incidence of periprocedural MI
      (1.1% vs. 4.1%, p<0.05) and major complication (5.9% vs. 9.4%, p<0.05), but
      longer hospital stays (6.5+/-5.1 vs. 3.1+/-2.6 days, p<0.05). CONCLUSIONS:
      Despite higher clinical and angiographic risk profiles in patients undergoing
      CABG, clinical results, morbidity, and mortality were comparable to those of
      PTCR. With evolving techniques, continued reevaluation of indications and
      outcomes are necessary.

PMID- 10063953
TI  - Secondary transmyocardial laser revascularization in the treatment of end-stage
      coronary artery disease.
AB  - Transmyocardial laser revascularization (TMR) has received more acceptance within
      the last few years. The vast majority of TMR users report impressive clinical
      benefits. The underlying mechanism for benefit by TMR, however, remains somewhat
      unclear. Between July 1994 and September 1997, 165 patients underwent TMR at our
      institution. In three of our TMR patients after an initial angina-free interval
      of 1 to 2 years we decided to repeat the laser operation. This article focuses on
      the three re-TMR patients who underwent a second TMR operation 12 to 14 months
      after the first one. Two of the three patients are well and experience
      significantly less angina than preoperatively.

PMID- 10063954
TI  - Functional hemodynamic assessment of the 21-mm and 23-mm CarboMedics Top Hat
      aortic prosthetic valve.
AB  - Between 1993 and 1996 the CarboMedics Top Hat supraannular aortic valve was
      implanted in 41 patients at the Wessex Cardiothoracic Centre (age, 39 to 74
      years; mean, 61.3+/-8.9 years). Comparisons of annular dimensions made at surgery
      indicate that conventional annular valve replacement would have required at least
      a size smaller valve. This was particularly marked when a prosthetic mitral valve
      was in place. Operative mortality was 2.4%. There were also three late deaths.
      Echocardiography before and after symptom-limited treadmill testing has been
      performed in 21 patients. The mean time to follow-up was 16.1 months. The Doppler
      derived indices of forward flow pre- and postexercise were expressed as mean+/
      standard deviation. For 23-mm valves the values were: peak valve gradient 21.43+/
      7.46 mm Hg and 35.86+/-14.4 mm Hg, aortic valve area 1.13+/-0.39 cm2 and 1.24+/
      0.54 cm2. For 21-mm valves the values were: peak valve gradient 24.84+/-8.2 mm Hg
      and 31.29+/-5.84 mm Hg, aortic valve area 1.08+/-0.44 cm2 and 0.95 +/-0.2 cm2.
      The Top Hat valve has a good hemodynamic profile at rest and during exercise.
      Surgical considerations make it particularly useful in patients with a small
      aortic annulus and in patients undergoing combined aortic and mitral valve
      replacement.

PMID- 10063955
TI  - Urgent surgical repair of postinfarction ventricular septal rupture: early and
      late outcome.
AB  - AIM: This retrospective analysis focuses on predictive factors of operative
      mortality and long-term survival after surgical repair of postinfarction
      ventricular septal rupture (VSR). METHODS: Sixty-seven patients (43 males, 24
      females) with VSR underwent surgical repair between December 1977 and December
      1995. The site of the rupture was anterior in 44 patients and posterior in 23.
      The mean interval between myocardial infarction (MI) and VSR was 3.6+/-4.1 days.
      Clinical condition on admission was critical in 63 patients (49 in cardiogenic
      shock). An intra-aortic balloon pump was inserted preoperatively in 54 patients.
      RESULTS: Operative mortality was 25% (17 patients). The main cause of death was
      cardiac failure. Factors influencing early deaths in univariate analysis were
      preoperative hemodynamic status (cardiogenic shock present in 30%; absent in 8%;
      p = 0.001), the location of the MI (anterior in 11.6%, posterior in 45.4%), the
      interval between infarction and surgery (<1 week was 33%, >1 week was 6.2%), and
      the response to initial active therapy. All patients were available for follow
      up. The actuarial survival rates at 1 and 5 years are 74.6%+/-5.3% and 66.2%+/
      6.2%, respectively. There were 12 late deaths and 40% were cardiac related. Two
      patients presented residual VSD (one reoperation). The left ventricular ejection
      fraction (LVEF) was mildly impaired in 9 patients. Three patients had moderate
      mitral insufficiency and two had moderate tricuspid insufficiency. CONCLUSION:
      Repair of the postinfarction VSR remains a challenge. Improvement should be
      rendered possible by optimizing techniques. Postoperative morbidity is high, and
      these patients require intensive hospital resources. The late results have been
      satisfactory.

PMID- 10063956
TI  - Is cardiac surgery justified in patients in the ninth decade of life?
AB  - BACKGROUND: Due to aging of the population the upper-age limit for cardiac
      operations has constantly been extended. In the current era of health care reform
      the ability to provide appropriate care for geriatric patients at acceptable
      costs is a major individual and societal concern. The objective of this study was
      to evaluate the results of cardiac surgery in octogenarians regarding overall
      morbidity and mortality as well as to quality of life. METHODS: Between February
      1992 and August 1995, 101 consecutive octogenarians underwent several types of
      cardiac operations. Operative procedures consisted of coronary artery bypass
      grafting (CABG) in 45 patients, valve replacement or repair in 33 patients, and
      combined CABG and combined procedures in 19 patients. All surviving patients were
      mailed a questionnaire 3 to 62 months (22.1+/-15.4 months) postoperatively
      concerning the postoperative course and quality of life (97.5% follow-up).
      RESULTS: The early mortality was 15.5% in the CABG group, 3.0% in the valve
      group, and 21.7% in the combined procedure group; 5-year actuarial survival was
      79.1% in the CABG group, 86.9% in the valve group, and 58.8% in the combined
      procedure group, respectively. The questionnaire sent to the survivors revealed
      that 81.0% of patients considered their functional status better or much better
      than before surgery. Of the survivors, 97.3% stated that according to their
      opinion the operation was worthwhile. CONCLUSION: Cardiac surgery is justified
      for carefully selected patients in the ninth decade of life. Although these
      patients are at increased risk of operative death and surgical complications
      compared with younger patients, the majority regain a life expectancy in the
      range of that of the global population. Furthermore, they are presented the
      chance to retain or maintain an independent lifestyle.

PMID- 10063957
TI  - Minimally invasive cardiac surgery with surgical ablation of atrial fibrillation.
AB  - Surgical ablation for atrial fibrillation with mitral valve operations has been
      often performed in patients who have chronic atrial fibrillation associated with
      mitral valve disease. We describe a case of the combined operation through a
      small incision. A 49-year-old woman presented with a 1-month history of left
      hemiplegia. Echocardiography confirmed mitral stenosis and electrocardiogram
      revealed atrial fibrillation. The duration of the atrial fibrillation before
      admission was 12 years. Mitral commissurotomy, removal of clots, and surgical
      ablation for atrial fibrillation was performed through an 8-cm right parasternal
      incision. The right femoral artery and vein were used for cannulation. Another
      cannula was inserted into the superior vena cava. The extended use of
      cryoablation was carried out instead of atriotomy or reanastomosis. The patient
      was extubated for 5 hours after the operation. Atrial fibrillation was converted
      to a sinus rhythm. On the basis of our experience, this procedure seemed
      promising.

PMID- 10063958
TI  - Long-term outcome following case management after coronary artery bypass surgery.
AB  - Patient outcome following coronary artery bypass grafting (CABG) has come under
      increasing governmental, social, and economic scrutiny. To insure quality patient
      outcome after CABG, many new policies and programs have been instituted. One of
      these, case management, was developed as a tool for identification and
      quantification of patient clinical sequences and resource utilization. This
      present study examines the influence of case management on length of stay and
      patient outcome following CABG. One hundred forty randomized, retrospectively
      analyzed CABG patients from 1990, prior to case management, were compared against
      140 age-and case-matched randomly controlled CABG patients from 1994 after case
      management was in place. Patients' demographics were similar. The outcome data
      showed that intensive care unit (ICU) use and total length of stay were
      significantly decreased. Furthermore, resource utilization as monitored by chest
      X-ray, electrocardiography, and laboratory testing were decreased as well.
      Finally, mortality was decreased despite an increase in risk-adjusted acuity of
      the patients. There appeared to be no effect of gender or age on the benefit
      derived from case management. These data demonstrate that the influence of case
      management is beneficial for resource utilization and patient outcome following
      CABG and that these types of patient care policy advancements should be
      encouraged.

PMID- 10063959
TI  - Reduction aortoplasty for moderately sized ascending aortic aneurysms.
AB  - Enlargement of the ascending aorta may coexist with concomitant valvular,
      coronary, or other cardiac diseases. If dilation is moderate (i.e., <6 cm
      diameter) and another cardiac procedure is being performed, we have reduced the
      diameter of the ascending aorta with an S-shaped incision and excision of the
      curves of the "S" as a modified Z-plasty. We have performed the procedure in 23
      patients with concomitant procedures including aortic valve replacement in 21 (1
      as a pulmonary autograft), coronary bypass in 1, and resection of subaortic
      stenosis in 1. There were 15 males and 8 females with a mean age of 53 years
      (range 8-67 years). The mean maximal preoperative diameter on transesophageal
      echocardiography was 5.0+/-0.7 cm (range 3.2-6.6 cm). The mean intraoperative
      postreduction diameter was 3.1+/-0.6 cm (range 2.1-4.1) (p<0.01). All patients
      tolerated their procedures well. Sixteen patients were studied by transthoracic
      echocardiography postoperatively. These patients had a mean intraoperative
      postreduction diameter of 2.9+/-0.65 cm that increased to 3.1+/-0.45 cm (p = NS)
      after a mean follow-up of 9.9+/-12.6 months. Of these, seven patients were
      studied >1 year postoperatively. Their mean intraoperative postreduction diameter
      of 2.9+/-0.5 cm increased to 3.1+/-0.35 cm (p = NS) after a mean follow-up of
      22.1+/-9.2 months. No known recurrences of the aneurysms have occurred. We feel
      this technique is valid in patients with moderate aortic dilation undergoing
      concomitant cardiac procedures and in whom more aggressive aortic interventions
      are not warranted.

PMID- 10063960
TI  - Right parasternal minithoracotomy for repair of atrial septal defect.
AB  - Various surgical approaches for repair of atrial septal defect (ASD) have
      recently been introduced for superior cosmetic and less invasive results. A
      technique for repair of isolated ASD through a small right parasternal
      minithoracotomy is described. In spite of the smaller incision, there is no need
      to use femoral cannulation or video-assisted endoscopy. This approach is simple,
      less invasive, and cosmetic. We believe that right parasternal minithoracotomy is
      a suitable alternative to a median sternotomy for ASD closure, especially in
      young male patients.

PMID- 10063961
TI  - The clamshell incision provides adequate exposure for aortic valve replacement
      and coronary revascularization.
AB  - The standard median sternotomy provides ready access to all surfaces of the heart
      and the ascending aorta. When cosmetic considerations, associated medical
      conditions, such as an esophageal stoma, or tracheostomy preclude use of the
      median sternotomy, a bilateral transverse sternotomy will provide excellent
      exposure of the entire ascending aorta and the lateral and inferior walls of the
      heart.

PMID- 10063962
TI  - Integrated approach for revascularization in multivessel coronary artery disease
      and porcelain aorta.
AB  - We report two cases in which combined beating heart revascularization of the left
      anterior descending artery (LAD) and percutaneous angioplasty of the non-LAD
      target arteries were adopted after the intraoperative detection of porcelain
      aorta and impossibility to complete surgical revascularization. This type of
      strategy preserves the benefits of surgical LAD grafting and complete
      revascularization and results in a simple and low-risk technical procedure in an
      otherwise challenging setting.

PMID- 10063963
TI  - Repair of a pseudoaneurysm of the ascending aorta after aortic valve replacement.
AB  - An elderly woman underwent an aortic valve replacement and 5 months later
      developed a pseudoaneurysm from the anterior aspect of the proximal ascending
      aorta (AA). The pseudoaneurysm was approached through a redo-median sternotomy,
      on cardiopulmonary bypass (CPB), mild hypothermia, and a beating heart, with a
      temporary fingertip occlusion of its ostium, and repaired successfully using
      mattress monofilament sutures enforced by pledgets. The standard approach to such
      pseudoaneurysms is a CPB and hypothermic circulatory arrest (HCA) prior to mid
      sternotomy, and replacement of the AA. But, when a pseudoaneurysm arises from a
      narrow ostium on the anterior aspect of the AA, as in this case, it can be
      sutured closed with pledgets under CPB with a mild hypothermia and a beating
      heart.

PMID- 10063964
TI  - Ruptured aneurysm of the ductus diverticulum into the pulmonary artery in a man:
      a successful repair.
AB  - Aneurysm of the ductus diverticulum in the adult is rare and its rupture is
      fatal. A 75-year-old man presented with congestive heart failure that suddenly
      occurred with a continuous murmur. Angiography showed a left-to-right shunt
      through a large thrombosed aneurysm of the ductus diverticulum (6 cm), and the
      pulmonary-to-systemic flow ratio was 2.6. Patch closure of the orifice (3x4 cm)
      of the aneurysm and repair of the perforated pulmonary artery were done
      emergently under hypothermic cardiopulmonary bypass with selective cerebral
      perfusion. He recovered uneventfully. Early recognition and early intervention
      should be indicated in this otherwise fatal condition.

PMID- 10063965
TI  - Cardiomyoplasty and implantable cardioverter defibrillator: efficacy and safety
      of concomitant device implantation: sudden death and cardiomyoplasty.
AB  - Sudden death represents a common event in the natural history of patients
      affected by chronic heart failure. Such an outcome also has been shown to
      characterize the follow-up of the cardiomyoplasty procedure. We report two cases
      of patients who had cardiomyoplasty and experienced witnessed episodes of
      ventricular arrhythmia at variable times after surgery (2 years and 2 months,
      respectively). In the first case, an implantable cardioverter defibrillator (ICD)
      was implanted subsequent to the arrhythmic episode, whereas the second patient
      had a combined cardiomyoplasty and ICD implantation procedure. In particular,
      this patient underwent a modified wrapping technique, herein described, because
      of a large left ventricular dilatation. In both cases, ventricular defibrillation
      did not affect the correct functioning of the implanted cardiomyostimulator. Our
      article confirms that ventricular arrhythmia is common in cardiomyoplasty
      patients. The combined use of a skeletal muscle stimulator and implantable
      defibrillator may therefore be effective in preventing arrhythmia-related sudden
      death without any concurrent effect on the correct functioning of the wrapped
      muscle/heart circuit, with likely benefit on long-term cardiomyoplasty patient
      survival.

PMID- 10063966
TI  - Musing while cutting.
AB  - Cardiac surgeons took to the heart and claimed an exclusive privilege to
      intervene. The task of cardiologists was to identify "candidates" and feed the
      great surgical machine. Recently, catheter surgery was developed and has fallen
      into the hands of cardiologists who became interventionists. Cardiac surgeons are
      concerned about shrinking domain, identity, and the future. The analysis of the
      current situation requires another look at old concepts: surgery, intervention,
      therapy, patients, invasiveness, etc., and a revision of the philosophy of the
      entire profession. Therapeutic plans comprise three interrelated components: the
      target, the bullet (therapeutic agent), and the gun (the way of delivering the
      bullet on target ). This description characterizes surgery as a way of
      delivering. If side effects are effects that do not affect the target, surgical
      procedures are mostly side effects, with significant morbidity. Future surgical
      rationales should reconcile target-specific therapy and minimal collateral
      damages: "minimal surgery!" or to use a new buzzword, "less invasive surgery."
      Cardiac surgery has focused on surgical practice and neglected the science of
      cardiology, missing opportunities for new research, new rationales, new
      techniques, and new territories. Surgeons must again become Renaissance men,
      involved in the entire field of cardiology, with a special skill in surgical
      techniques. Cardiac surgeons should no longer confine their practice to the
      delivering end. This end does not, any more, justify the means.

PMID- 10063967
TI  - FHITness and cancer.
AB  - In early 1996, the Fragile Histidine Triad or FHIT gene (pronounced FIT) was
      cloned and shown to straddle the most fragile human chromosome site at chromosome
      band 3p14.2. The exceptionally large FHIT locus also encompasses a hereditary
      renal carcinoma associated chromosome translocation breakpoint and is very
      frequently altered by internal deletions in the most common human cancers.
      Germline alteration of one allele in familial cancer and deletions within the
      gene in sporadic cancers are hallmarks of tumor suppressor genes. Some of the DNA
      and RNA alterations exhibited by the FHIT gene in cancers showed features not
      previously encountered for known tumor suppressor genes, prompting a number of
      investigators to reject FHIT as a suppressor gene. However, evidence continues to
      accumulate, demonstrating that FHIT inactivation occurs in the majority of lung,
      gastric, cervical, and kidney carcinomas and that replacement of Fhit expression
      in such cancer cells suppresses their tumorigenicity.

PMID- 10063968
TI  - Schedule-dependent synergism and antagonism between paclitaxel and methotrexate
      in human carcinoma cell lines.
AB  - Paclitaxel and methotrexate are active against a variety of solid tumors. Because
      of differences in their mechanisms of action and toxicity profiles, the
      combination of these two agents has clinical potential. Clinical studies of this
      combination are in progress. We studied the optimal schedule of paclitaxel and
      methotrexate in combination at various schedules in vitro using human lung cancer
      A549, breast cancer MCF7, ovarian cancer PA1, and colon cancer WiDr cells. Cells
      were simultaneously exposed to paclitaxel and methotrexate for 24 h and
      sequentially exposed to paclitaxel for 24 h followed by methotrexate for 24 h or
      vice versa. Cell growth inhibition after 5 days was determined by a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of
      drug combinations at the concentration of drug that produced 80% cell growth
      inhibition (the IC80 level) were analyzed by the isobologram method. The
      simultaneous exposure to paclitaxel and methotrexate produced additive to
      antagonistic effects in the A549 and PA1 cells, and antagonistic effects in the
      MCF7 and WiDr cells. The sequential exposure to paclitaxel followed by
      methotrexate produced additive effects in all four cell lines. The reverse
      sequence produced synergistic effects in the A549, MCF7, and WiDr cells, and
      additive effects in the PA1 cells. These findings suggest that a sequential
      administration of methotrexate followed by paclitaxel may be the appropriate
      schedule for this combination. On the basis of the observed in vitro synergism,
      further in vivo and clinical studies are necessary to clarify the toxicity and
      proposed antitumor effects of this schedule.

PMID- 10063969
TI  - Taurine attenuates fanconi syndrome induced by ifosfamide without compromising
      its antitumor activity.
AB  - Nephrotoxicity is an important clinical side effect of the chemotherapeutic agent
      ifosfamide (IFO). Taurine (TAU), an antioxidant amino acid, was used in the
      present study to evaluate its beneficial effects against the Fanconi syndrome
      (FS) induced by IFO. The rationale of use of TAU was based on its reported
      antioxidant effect and the fact that the kidney tends to waste amino acid in IFO
      induced FS. Rats received daily injection of IFO (50 mg/kg, IP) for 5 days with
      or without oral supplementation of 1% TAU in the drinking water for 7 days before
      IFO and daily thereafter. The results demonstrated that IFO induced a FS
      characterized by wasting off glucose, electrolytes, and organic acids, along with
      elevated serum creatinine and urea, and decreased creatinine clearance rate. TAU
      markedly ameliorated the severity of renal dysfunction induced by IFO, with a
      significant decrease in total and fractional excretion of Na+, K+, PO4(-3), and
      glucose, decreased serum creatinine, urea, and albumin, and increased creatinine
      clearance rate. TAU significantly improved the IFO-induced renal glutathione
      (GSH) depletion, renal malondialdehyde accumulation, and body weight loss. On the
      other hand, in Ehrlich ascites carcinoma (EAC)-bearing mice, IFO (50 mg/kg/day,
      IP on days 1-4 and 15-18) demonstrated antitumor activity as a single agent. No
      reduction in IFO activity was observed with the supplementation of TAU (1%) in
      the drinking water. Furthermore, the use of TAU not only maintained high IFO
      antitumor activity but also was associated with lower toxicity as manifested by
      less body weight loss and less mortality rate of IFO therapy compared with IFO
      when given alone. These observations demonstrate that oral supplementation of TAU
      can protect against IFO-induced renal dysfunction and maintain the antitumor
      activity of IFO.

PMID- 10063970
TI  - Inhibitory effect of vasoactive intestinal polypeptide (VIP) on experimental
      liver metastasis by murine colon 26-L5 carcinoma cells.
AB  - We previously reported that vasoactive intestinal polypeptide (VIP) significantly
      inhibited Matrigel invasion and haptotactic migration of murine colon 26-L5
      carcinoma in vitro. To extend our study, we investigated the inhibitory
      mechanisms of VIP on Matrigel invasion of colon 26-L5 carcinoma, and the effect
      on metastatic properties of the tumor cells. VIP inhibited the invasion of the
      tumor cells in a concentration-dependent manner without affecting their growth,
      and achieved approximately 50% reduction at 10(-6) M. VIP also suppressed cell
      motility with a similar inhibition rate to the invasion assay. Time course study
      revealed that the motility was reduced by 40% when the tumor cells were
      preincubated with 10(-6) M VIP for 3 h. In contrast, 6-h pretreatment with 10(-6)
      M VIP caused the increased ability of the adhesion to both fibronectin and
      laminin with a 50% enhancement. A large amount of VIP1 receptor transcripts was
      expressed in the cells, whereas VIP2 receptor was undetectable, by RT-PCR and
      subsequent Southern blot hybridization. A specific antagonist for VIP1 receptor
      reversed the suppressed motility induced by VIP. Cryostat sections showed that
      the 3-h pretreatment of tumor cells with VIP caused the reduction of the arrest
      in the livers at 6 h after the tumor inoculation into a portal vein of mice. VIP
      could prevent the experimental liver metastasis of the tumor cells in a dose
      dependent manner. The cells pretreated with 10(-6) M VIP for 3 h also showed the
      reduced ability of the liver metastasis. These results suggest that VIP could
      block the invasion and the metastasis of colon 26-L5 carcinoma through
      suppression of their motility.

PMID- 10063971
TI  - The effects of gemcitabine and TPA on PKC signaling in BG-1 human ovarian cancer
      cells.
AB  - Protein kinase C (PKC) signaling pathways play an important role in cell survival
      and anticancer drug-induced apoptosis. We observed in clonogenicity assays of BG
      1 human ovarian cancer cells that gemcitabine cytotoxicity was increased
      synergistically when drug treatment was followed or preceded by a 24-h exposure
      to 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA). Coincubation of 10 nM TPA
      with pharmacological inhibitors of PKC abrogated the synergism of TPA and
      gemcitabine. These observations prompted further investigation of PKC signaling
      events linked to TPA and gemcitabine cytotoxicity in BG-1 cells. Because PKC
      isoforms are differentially expressed in various cell types, we determined that
      BG-1 cells express the alpha, beta, delta, epsilon, and zeta isoforms of PKC. In
      addition, 1-h exposures to 10 microM gemcitabine triggered cytosol to membrane
      translocation of PKC isoforms alpha, delta, and epsilon, indicating these
      isoforms were activated by gemcitabine. We also explored the PKC mechanism(s)
      responsible for the synergism of TPA and gemcitabine, and determined that
      treatment with 10 nM TPA for 24 h in BG-1 cells: 1) downregulated PKCdelta and
      PKCalpha, without affecting PKCepsilon, 2) did not affect cell cycle distribution
      into S phase. 3) increased extracellular signal-regulated kinase signaling, and
      4) increased intracellular alkaline phosphatase activity, a biochemical marker of
      cellular differentiation. Chronic exposure (24 h) to TPA enhanced gemcitabine
      cytotoxicity, perhaps by inducing cellular differentiation pathways in BG-1
      cells. Therefore, the use of differentiating agents in combination with
      gemcitabine may improve its clinical efficacy.

PMID- 10063972
TI  - Evaluation of pGL1-TNF-alpha therapy in combination with radiation.
AB  - Long-term control of high-grade brain tumors is rarely achieved with current
      therapeutic regimens. In this study a new plasmid-based human tumor necrosis
      factor-alpha (TNF-alpha) expression vector was synthesized (pGL1-TNF-alpha) and
      evaluated together with radiation in the aggressive, rapidly growing C6 rat
      glioma model. pGL1-TNF-alpha was successfully transfected into C6 cells in vitro
      using a cationic polyamine method. Expression was detected up to 7 days and
      averaged 0.4 ng of TNF-alpha in the culture medium from 1x10(5) cells. The
      expressed protein was biologically functional, as evidenced by growth inhibition
      of L929, a TNF-alpha-susceptible cell line. Using fluorescence-labeled monoclonal
      antibodies and laser scanning cytometry, we confirmed that both the P55 and P75
      receptors for TNF-alpha were present on the C6 cell membrane. However, the
      receptors were present at low density and P55 was expressed more than the P75
      receptor. These findings were in contrast to results obtained with TNF-alpha
      susceptible L929 cells. Tests in athymic mice showed that pGL1-TNF-alpha
      administered intratumorally 16-18 h before radiation (each modality given three
      times) significantly inhibited C6 tumor progression (P<0.05). This effect was
      more than additive, because pGL1-TNF-alpha alone did not slow tumor growth and
      radiation alone had little effect on tumor growth. These results indicate that
      pGL1-TNF-alpha has potential to augment the antitumor effects of radiation
      against a tumor type that is virtually incurable.

PMID- 10063974
TI  - Comparison of the results of the Weil and Helal osteotomies for the treatment of
      metatarsalgia secondary to dislocation of the lesser metatarsophalangeal joints.
AB  - We retrospectively reviewed the outcome of 30 patients who were treated
      surgically for metatarsalgia resulting from dislocation of one or more lesser
      metatarsophalangeal (MTP) joints. We used two treatments, including an osteotomy
      of the metatarsal head (Weil osteotomy, N = 15) or an osteotomy of the metatarsal
      shaft (Helal osteotomy, N = 15). Before surgery, all patients had been treated
      with various nonoperative modalities for a minimum of 6 months. Between 1991 and
      1993, 15 consecutive patients underwent a Helal osteotomy (22 metatarsals), and
      15 consecutive patients were subsequently treated between 1994 and 1995 with a
      Weil osteotomy (25 metatarsals). All patients were evaluated clinically and
      radiographically at a mean follow-up period of 22 months (range, 12-39 months),
      noting especially persistent subluxation or dislocation, recurrent metatarsalgia,
      and transfer lesions. Patients managed with a Weil osteotomy had significantly
      higher satisfaction (P = 0.049), lower incidence of recurrent metatarsalgia (0
      vs. 27%, P = 0.107), and fewer transfer lesions (0 vs. 41%, P = < 0.001) than
      those managed with a Helal osteotomy. Furthermore, those managed with the Weil
      procedure had a higher percentage of radiographic reduction and maintenance of
      the MTP joint dislocation (21 of 25, 84%; vs. 8 of 22, 36%; P = 0.002) than those
      managed with the Helal procedure. In the Weil group, there was also no malunion
      or pseudoarthrosis; in the Helal group there were five malunions and three
      pseudoarthroses. Although the follow-up period for the Weil osteotomy (15 months)
      was shorter than that for the Helal osteotomy (26 months), the former group had
      higher American Orthopaedic Foot and Ankle Society forefoot scores, which were
      significantly different from the results attained with the Helal osteotomy. A
      telephone update was performed on the Weil osteotomy group at an average of 27
      months postsurgery, and no patient had experienced changes since the clinical
      follow-up. We concluded that the Weil procedure is a satisfactory method for
      correcting metatarsalgia caused by dislocation of the MTP joint and that, because
      of the high complication rate, the Helal osteotomy is not an acceptable procedure
      for correcting this condition.

PMID- 10063975
TI  - Dorsiflexion metatarsal osteotomy for treatment of recalcitrant diabetic
      neuropathic ulcers.
AB  - Twenty diabetic patients underwent 22 dorsiflexion metatarsal osteotomies for
      treatment of chronic persistent or recurrent neuropathic forefoot ulcers. Mean
      duration of nonoperative treatment was 13 months. The procedure consisted of
      irrigation and debridement of the ulcer followed by basilar closing wedge
      metatarsal osteotomy performed through a dorsal approach. At follow-up, complete
      ulcer healing was noted in 21 cases (95%) at an average of 40 days
      postoperatively. Complications occurred in 15 cases (68%). The main problems
      encountered postoperatively were acute Charcot disease (32%) and deep wound
      infections (14%). Transfer lesions under adjacent metatarsal heads developed in
      two cases (9%). One ulcer (5%) failed to heal secondary to vascular insufficiency
      and eventually required a below the knee amputation after a failed
      revascularization attempt. Loss of screw fixation occurred in one patient (5%)
      but acceptable metatarsal alignment was maintained and the ulcer healed
      uneventfully. There were no cases of ulcer recurrence. The results of this study
      suggest that dorsiflexion metatarsal osteotomy is a reliable salvage procedure
      for the treatment of recalcitrant neuropathic forefoot ulcers that have failed an
      adequate trial of nonoperative treatment. This procedure is associated with a
      high complication rate, as would be expected in this patient population.

PMID- 10063976
TI  - Biomechanical consequences of plantar fascial release or rupture during gait.
      Part II: alterations in forefoot loading.
AB  - With a model using feet from cadavers, we tested the hypothesis that plantar
      fascial release or rupture alters the loading environment of the forefoot during
      the latter half of the stance phase of gait. The model simulated the position and
      loading environment of the foot at two instants: early in terminal stance
      immediately after heel-off and late in terminal stance just preceding
      contralateral heel strike. Eight feet were loaded at both positions by simulated
      plantar flexor contraction, and the distribution of plantar pressure was measured
      before and after progressive release of the plantar fascia. Strain in the
      diaphysis of the second metatarsal was also measured, from which the bending
      moments and axial force imposed on the metatarsal were calculated. Cutting the
      medial half of the central plantar fascial band significantly increased peak
      pressure under the metatarsal heads but had little effect on pressures in other
      regions of the forefoot or on second metatarsal strain and loading. Dividing the
      entire central band or completely releasing the plantar fascia from the calcaneus
      had a much greater effect and caused significant shifts in plantar pressure and
      force from the toes to beneath the metatarsal heads. These shifts were
      accompanied by significantly increased strain and bending in the second
      metatarsal. Complete fasciotomy increased the magnitude of strain in the dorsal
      aspect of the second metatarsal by more than 80%, suggesting that plantar fascial
      release or rupture accelerates the accumulation of fatigue damage in these bones.
      Altered forefoot loading may be a potential complication of plantar fasciotomy.

PMID- 10063977
TI  - Reconstruction of the lateral ankle ligaments using a split peroneus brevis
      tendon graft.
AB  - Thirty-one consecutive ankles in 30 patients with chronic lateral ankle
      instability were reconstructed using a split peroneus brevis tendon graft. All
      patients had pain and instability despite adequate treatment and a rehabilitation
      program. Six patients had clinical and radiographic evidence of associated
      subtalar laxity. Four patients (four ankles) had prior Brostrom ligament
      reconstructions. The average time from the initial injury or treatment to surgery
      was 23 months. At a mean follow-up of 44 months (range, 24-64 months), the
      functional results included excellent in 20 ankles, good in 9, fair in 1, and
      poor in 1. Ankle stability, which did not deteriorate with time, was achieved in
      30 of 31 ankles. This procedure is simple, safe, and reliable with a 94% good to
      excellent clinical result and 97% mechanical stability. It is an excellent
      reconstruction choice for those individuals with high demand ankles, with a
      longstanding ankle instability with or without subtalar instability, and for
      failed primary reconstruction.

PMID- 10063978
TI  - Involvement of the foot and ankle in patients with Gaucher disease.
AB  - Of 48 children with type I Gaucher disease treated at our hospital, 11 had
      involvement of the foot and ankle that first appeared in adolescence. Follow-up
      ranged from 3 to 27 years (average, 10 years). We reviewed their clinical and
      radiographic histories. Patients presented with four types of pain: six (7 events
      of pain) complained of dull pain defined as nonspecific; seven (11 events) had
      severe pain caused by bone crisis; two (2 events) had moderate progressive pain
      caused by pathological fractures; and one had painful swollen ankles caused by
      degenerative arthritis. Greater awareness of these complications in patients with
      Gaucher disease will prevent misdiagnosis and lead to early treatment.

PMID- 10063979
TI  - Cartilage and synovium of the peroneocuboid joint: an anatomic and histological
      study.
AB  - The surface area, thickness, and composition of the articular cartilage of the
      peroneocuboid articulation and the location of the synovium were investigated in
      15 cadaver foot specimens. The articulations of the medial side of the peroneus
      longus tendon and lateral side of the cuboid were covered with fibrous and
      hyaline cartilages, respectively. On the lateral tuberosity of the cuboid, there
      is a facet that has 79.37+/-20.24 mm2 articular cartilage area with an oval shape
      to conform to that of the articular surface of the peroneus longus tendon
      (articular cartilage area, 67.35+/-28.53 mm2) with which it articulates. The mean
      thickness of the articular cartilage of the peroneus longus tendon and cuboid was
      0.34+/-0.08 and 0.52+/-0.07 mm, respectively. The peroneocuboid joint has its own
      joint capsule. The synovial cavity does not communicate with the sheath of the
      peroneus longus tendon. Synovial membranes were attached to the margins of the
      articular surfaces of the cuboid immediately peripheral to the cartilage region.

PMID- 10063980
TI  - Medial longitudinal arch of the foot: stationary versus walking measures.
AB  - We describe the characteristics of the medial longitudinal arch (MLA) of the
      right foot in 19 healthy men while sitting/partial bodyweight, standing/full
      bodyweight, and during the stance phase of walking. Three measurements were
      selected as representative of the MLA, including: height of the arch, length of
      the arch, and supranavicular angle. Mean values were calculated in three
      dimensions for each measure in the sitting and standing conditions and for the
      minimum value of each measure in the walking condition. Patterns measured during
      walking had high association (r = 0.999) and could be related to phases of
      stance. In the stationary conditions, the MLA varied significantly (P<0.001). No
      significant relationship of arch height, arch length, or supranavicular angle was
      found between sitting and standing or between stationary and walking conditions.
      It was concluded that none of the static variables could be used to predict
      others and that static measures of the MLA do not predict the dynamic motion of
      the MLA. The MLA may not be a reasonable indicator of behavior or motion of the
      foot.

PMID- 10063981
TI  - Natural history of the rearfoot angle: preliminary values in 150 children.
AB  - The degree of valgus in the heel during weightbearing (the rearfoot angle) is
      commonly used as an angular criterion in the evaluation and treatment of flatfoot
      in children and adults. The rearfoot angle has been frequently reported to reduce
      with age to a vertical heel position attained at approximately 7 years old. The
      present study evaluated the rearfoot angle in 150 healthy children (age range, 6
      16 years). The average rearfoot angle for all children in this study was 4
      degrees of valgus (SD, 1.1 degrees; range, 0 degree - 9 degrees of valgus). There
      was no significant difference in the rearfoot angle in children of different
      ages. The rearfoot angle did not reduce to the vertical heel position by age 7 as
      had been reported previously.

PMID- 10063982
TI  - Effect of ankle and knee position on tension in the Achilles tendon.
AB  - The purpose of this study was to evaluate the relative contributions of ankle and
      knee position to tension in the Achilles tendon and to determine whether there
      exists a position of plantarflexion at which the passive tensioning effect of
      knee extension is eliminated. Seven matched pairs of fresh-frozen cadaver lower
      extremities were tested. A buckle transducer was used to measure forces in the
      tendon throughout the full range of knee motion, with the hindfoot fixed.
      Positioning the hindfoot in 20 degrees to 25 degrees of plantarflexion
      effectively eliminates tension in the Achilles tendon, regardless of knee
      position. This information is directly applicable both to the nonoperative
      treatment of ruptures of the Achilles tendon employing a short leg cast and to
      surgical repairs, in which tension must be controlled precisely.

PMID- 10063983
TI  - Kenneth A. Johnson Memorial Lecture. The unfinished task.

PMID- 10063984
TI  - Ipsilateral fibular slide grafts in the management of distal fibula lesions.

PMID- 10063985
TI  - Capsular closure after hallux valgus surgery.

PMID- 10063986
TI  - The crescentic shelf osteotomy.

PMID- 10063987
TI  - Hyperhomocysteinemia, atherosclerosis and thrombosis.
AB  - High plasma levels of homocysteine are the results of the interplay between
      congenital and environmental factors. In the last two decades, a growing amount
      of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor
      of thromboembolic diseases. Case-control and cross-sectional studies clearly
      indicated that mild-to-moderate hyperhomocysteinemia is associated with
      heightened risk of both arterial and venous thrombosis. On the other hand,
      prospective studies did not unequivocally show that hyperhomocysteinemia is
      associated with a high thrombotic risk. Therefore, additional studies are needed
      to define whether hyperhomocysteinemia is a risk factor for thrombosis,
      especially of the venous circulation. Among these, prospective cohort studies
      will clarify better the temporal relationship between high homocysteine levels
      and the thrombotic event. Most importantly, however, randomized, placebo
      controlled, double-blind trials of the effects of homocysteine-lowering vitamins
      on the thrombotic risk are urgently needed. Not only will they help in defining
      whether the relationship between hyperhomocysteinemia and thrombosis is causal,
      they will also have a potential dramatic impact in the prevention of
      thromboembolic events.

PMID- 10063988
TI  - Hemostasis in the mouse (Mus musculus): a review.

PMID- 10063989
TI  - Compound heterozygosity for one novel and one recurrent mutation in a Thai
      patient with severe protein S deficiency.
AB  - Homozygous or compound heterozygous protein S (PS) deficiency is a very rare
      disorder in the anticoagulant system, that can lead to life-threatening
      thrombotic complications shortly after birth. This report describes the results
      of the genetic analysis of the PROS 1 genes in a Thai girl patient. She was
      reported in 1990 as the first case with homozygous PS deficiency and neonatal
      purpura fulminans. In the present report, we identified the mutations in this
      patient by direct sequencing of PCR products representing all 15 exons of the
      PROS 1 gene and their flanking intronic regions. The patient turned out to be
      compound heterozygous for two null mutations. One allele contained a novel
      sequence variation, an A-insertion in an A5-tract covering codon 146 and 147,
      that results in a frameshift and a stop codon (TAA) at position 155. The other
      allele contained a nonsense mutation in exon 12 by a transition at codon 410 CGA
      (Arg) to TGA (stop). Cosegregation of PS deficiency with these two genetic
      defects was observed in her family.

PMID- 10063990
TI  - The factor V gene A4070G mutation and the risk of venous thrombosis.
AB  - The A4070G polymorphism in exon 13 of the factor V (FV) gene, which replaces His
      by Arg at position 1299 of the B domain, was recently shown to influence
      circulating FV levels and to contribute to the activated protein C (APC)
      resistance phenotype. We examined the impact of this polymorphism in a population
      of unselected patients with venous thromboembolic disease (VTE). The prevalence
      of the G4070 (R2) allele was determined in 205 patients and 394 healthy subjects
      of similar age and sex distribution. Thirty-seven patients (18%) were
      heterozygous for the R2 allele and 1 (0.5%) was homozygous. Forty-four controls
      (11.2%) were heterozygous for the R2 allele and 1 (0.2%) was homozygous. Thus,
      the allelic frequency was significantly higher in the patients with VTE than in
      the healthy controls, with respective values of 9.5% and 5.8%. The odds ratio was
      1.8 (95% CI: 1.1-2.8, p = 0.02), pointing to an increased risk of VTE in carriers
      of the R2 allele. After excluding subjects with putative or confirmed gene
      defects (mainly the FV R506Q mutation), the R2 allele was still a risk factor for
      VTE in the remaining patients, with an odds ratio of 2.0 (95% CI: 1.2-3.5, p =
      0.01), demonstrating that this polymorphism is itself a risk factor. This study
      also confirms that the R2 allele influences APC resistance (APCR) in the absence
      of the FV R506Q mutation.

PMID- 10063991
TI  - Incidence of venous thromboembolism in families with inherited thrombophilia.
AB  - The risk of spontaneous or risk-period related venous thromboembolism in family
      members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S
      (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We
      performed a retrospective cohort study in family members (n = 793) of unselected
      patients with a documented venous thromboembolism and one of these deficiencies
      to make an estimate of this risk. The annual incidences of total and spontaneous
      venous thromboembolic events in carriers of AT, PC or PS defects (n = 181) were
      1.01% and 0.40%, respectively, as compared to 0.10% and 0.04% in non-carriers,
      respectively (relative risks both 10.6). In carriers of Factor V Leiden (n =
      224), the annual incidences of total and spontaneous venous thromboembolism were
      0.28% and 0.11%, respectively, as compared to 0.09% and 0.04% in non-carriers,
      respectively (relative risks 2.8 and 2.5). Additional risk factors
      (immobilisation, surgery and trauma: oral contraceptive use; and pregnancy/ post
      partum) increased the risk of thrombosis in carriers of AT, PC and PS defects as
      compared to non-carriers (relative risks 8.3, 6.4 and 8.2, respectively). Oral
      contraceptive use and pregnancy/ post-partum period increased the risk of
      thrombosis in carriers of Factor V Leiden to 3.3-fold and 4.2-fold, respectively,
      whereas other risk factors had only a minor effect. These data lend some support
      to the practice of screening family members of symptomatic carriers of a AT, PC
      and PS deficiency. For family members of symptomatic carriers of Factor V Leiden,
      screening does not seem to be justified except for women in fertile age.

PMID- 10063992
TI  - Low levels of heparin-releasable tissue factor pathway inhibitor in young
      patients with thrombosis.
AB  - An association between deficiency of tissue factor pathway inhibitor (TFPI) and
      thrombosis has not been clearly demonstrated in humans, but previous studies have
      focused on the measurement of plasma TFPI, which is only a small part of the
      total body TFPI. The major fraction of this natural anticoagulant can be measured
      in plasma after release by heparin injection. To investigate if deficiency of
      heparin-releasable TFPI is associated with thrombosis. we measured TFPI activity
      in plasma before and 10 min after intravenous injection of 7500 IU unfractionated
      heparin in 64 young patients with venous thrombosis, 49 young patients with
      arterial thrombosis and 38 healthy individuals. Post-heparin TFPI activity levels
      were significantly lower in the group of patients with venous thrombosis than in
      controls (mean+/-SD: 230%+/-39 vs 260%+/-34, p = 0.0002), whereas there was no
      difference for patients with arterial thrombosis. Defining the normal range as
      the mean+/-2 SD of TFPI activity in controls, twelve patients had low post
      heparin TFPI activity levels, seven with venous and five with arterial
      thrombosis. Low levels of TFPI activity were confirmed by immunoassay in six of
      the seven patients with venous thrombosis and two of the five patients with
      arterial thrombosis, and were present also in at least one first degree relative
      of six patients, suggesting that the defect might be inheritable. However, the
      causative role of low heparin-releasable TFPI remains uncertain, because co
      segregation of the defect with thrombotic symptoms could not be demonstrated in
      the small number of families studied.

PMID- 10063993
TI  - The factor II G20210A and factor V G1691A gene transitions and coronary heart
      disease.
AB  - BACKGROUND: G to A transitions at nucleotide position 20210 of the factor II
      (Fll) gene and at 1691 of the factor V (FV) gene have been shown to be associated
      with an increased risk of venous thrombosis. Since it is still unclear whether
      both gene variations are also related to an increased risk of coronary heart
      disease (CHD), we studied the relation of both gene variations to coronary artery
      disease (CAD) and myocardial infarction (MI) in a sample of 2210 male individuals
      whose coronary anatomy were defined by coronary angiography. RESULTS: In the
      total sample, the FII G20210A gene variation was not associated with the presence
      or the extent of CAD, the latter defined either by the degree of vessel disease
      or by a CHD score according to Gensini. However, individuals with unfavourable
      lipid profiles showed pronounced differences in CHD scores between GA
      heterozygotes and GG homozygotes: this observation applied in particular to
      younger patients (<62 years; mean age of total sample) who simultaneously had low
      apoAI/apoB ratios (< 1.19, mean value) and high Lp(a) plasma levels (>28 mg/dl;
      mean value). In addition, in subjects without acetylsalicylic acid treatment GA
      heterozygotes had clearly higher CHD scores than AA genotypes. Further
      restriction to smokers, to subjects with high fibrinogen plasma levels (>3.47
      g/l; mean value) or to patients with high glucose concentrations (>112 mg/dl;
      mean value) tended to increase the difference in CHD score between FII G20210A
      genotypes. An association of the FII G20210A gene variation with non-fatal MI was
      not observed. In the total sample and in high and low risk subpopulations, an
      association of the FV G1691A gene variation was not detected neither with
      presence and extent of CAD or with nonfatal MI. CONCLUSION: The importance of the
      factor II G20210A gene variation for CHD may be restricted to individuals with
      major cardiovascular risk factors. In addition, the present study did not
      strengthen the hypothesis of the factor V G 1691 A transition as a risk factor of
      coronary heart disease neither in the total sample nor in subgroups of
      individuals who were at high or low risk of CHD.

PMID- 10063994
TI  - Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an
      antithrombotic agent--a pilot study in the setting of coronary angioplasty.
AB  - AIM OF THE STUDY: To assess the antithrombotic properties of SR90107/ORG31540. a
      sulfated pentasaccharide, which enhances specifically antithrombin III mediated
      inactivation of factor-Xa, in a clinical setting known to promote arterial
      thrombosis, i.e. coronary angioplasty. METHODS AND RESULTS: Percutaneous
      transluminal coronary angioplasty (PTCA) was carried out with conventional
      balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide, and
      500 mg intravenous aspirin. Heparin was not allowed before, during PTCA, and
      within 24 h after PTCA. The primary end point was the rate of abrupt vessel
      closure during and within 24 h after the procedure. The sample size was set at 60
      evaluable patients, in order to be able to conclude with a good level of
      confidence (>95%) that the abrupt vessel closure rate was less than 10%, if less
      than 3 abrupt vessel closures were observed. Seventy-one patients were included
      in the study, of whom 10 needed elective stenting, and were not considered as
      evaluable for efficacy. Two out of the 61 remaining evaluable patients
      experienced acute vessel closure during the study period [3.28%, 95% confidence
      interval (0.4%; 11.4%)]. No major bleeding occurred. The drug plasma
      concentrations reached 1.91+/-0.39 mg/], 10 min after pentasaccharide injection,
      and decreased on average to 1. 18+/-0.27 mg/l at 2 h, and to 0.36+/-0.11 mg/l at
      23 h after administration of pentasaccharide. Activated clotting time (ACT) and
      activated partial thromboplastin (aPTT) time remained within normal range.
      Thrombin-antithrombin complex levels fell from 22+/-17.1 to 4.5+/-3.4 microg/ml,
      prothrombin fragment 1+2 levels decreased from 2.15+/-1.01 to 1.73+/-0.87, and
      activated factor VII levels decreased from 43.4+/-16.8 mU/ml to 18.9+/-7.3 mU/ml
      respectively from baseline to 2 h following injection of the tested drug.
      CONCLUSIONS: Administration of pentasaccharide led to the inhibition of thrombin
      generation without modification of aPTT and ACT. The rate of abrupt vessel
      closure was within range of rates reported in historical series. Thus we conclude
      that the anti-thrombotic activity of pentasaccharide, as shown in this pilot
      trial in the setting of coronary angioplasty, deserves further investigation.

PMID- 10063995
TI  - Performances of the fibrin monomer test for the exclusion of pulmonary embolism
      in symptomatic outpatients.
AB  - Many studies have shown that D-dimer determinations can be used for the exclusion
      of venous thromboembolism in symptomatic outpatients, depending however on the
      method of D-dimer measurement. Another related assay, the Fibrin Monomer test
      which measures soluble fibrin levels in plasma by ELISA, is now available. We
      have evaluated the performances of this assay for the exclusion of pulmonary
      embolism (PE) in 426 consecutive outpatients presenting at the emergency ward of
      our institution. Diagnosis of PE was made by D-dimer measurement, compression
      ultrasonography, lung scintigraphy, venography and pulmonary angiography. With a
      cut-off of 3 microg/ml. the sensitivity and the negative predictive value were
      both 100% (95% CI: 97.1-100 and 96.3-100 respectively) and the specificity 33%
      (95 % CI: 25.7-38.1). With 4 microg/ml, the corresponding figures were 98.4 (95%
      CI: 94.4-99.8), 98.3 (95% CI: 94.1-99.8) and 39% (95% CI: 33.6-44.7)
      respectively. The prevalence of PE was 30%, the exclusion rates were 23 and 27%
      for either cut-off. When compared with a reference D-dimer assay (Asserachrom D
      Di), a good correlation was observed. In conclusion, this is the first study
      suggesting the interest of this Fibrin Monomer test to rule out PE; these
      results, however, need to be confirmed by other studies.

PMID- 10063996
TI  - Post-DDAVP thrombocytopenia in type 2B von Willebrand disease is not associated
      with platelet consumption: failure to demonstrate glycocalicin increase or
      platelet activation.
AB  - Thrombocytopenia is frequently reported in type 2B von Willebrand disease (vWD),
      and thought to be related to the abnormally high affinity of 2B von Willebrand
      factor (vWF) for platelet GPIb-IX. To gain an insight into the nature of this
      thrombocytopenia, we measured plasma glycocalicin (GC) levels (as a marker of
      platelet turnover), and platelet surface expression of the alpha granule protein
      P-selectin (as a marker of platelet activation) in 9 patients with type 2B vWD
      before, and in 4 patients also following the infusion of 1-desamino-8-d-arginine
      vasopressin (DDAVP). Three patients presented a persistent decrease of platelet
      counts in the resting condition. GC levels were within the normal range,
      regardless of the platelet counts, in all but one patient who presented, on the
      other hand, a normal platelet count. Moreover, platelets expressed normal amounts
      of P-selectin on their surface, regardless of platelet counts. These findings
      suggest that the thrombocytopenia observed in type 2B vWD is not due to platelet
      activation and subsequent consumption in circulation. Despite a significant,
      albeit transient, decrease in platelet count, DDAVP did not induce an increase in
      plasma GC levels, nor enhance P-selectin expression. These observations indicate
      that the acute post-DDAVP thrombocytopenia in type 2B vWD is not related to
      platelet activation and consumption. We advance that the post-DDAVP 2B vWF is
      hemostatically more active, and able to induce agglutination but not aggregation
      of circulating platelets. This would explain both the prompt recovery of basal
      platelet counts after the post-DDAVP decrease, and the lack of reported
      thrombotic complications in this disorder. Therefore, even though 2B vWF is
      characterized by an enhanced affinity for the platelet surface, its binding to
      platelet GPIb-IX in the soluble phase is not able to induce true platelet
      aggregation: vWF thus appears to be mainly an adhesive protein, rather than an
      aggregating agent.

PMID- 10063997
TI  - Safety and efficacy of continuous infusion of a combined factor VIII-von
      Willebrand factor (vWF) concentrate (Haemate-P) in patients with von Willebrand
      disease.
AB  - We studied the safety and efficacy of treatment with continuous infusion of a von
      Willebrand factor (vWF) concentrate Haemate-P in patients with von Willebrand
      disease (vWD). Three patients with mild and 5 patients with severe forms of vWD,
      were treated with continuous infusion of Haemate-P by minipump. The indications
      for treatment were: to prevent bleeding during 9 surgical procedures or 1 vaginal
      delivery in 6 patients and to treat 2 bleeding episodes in 2 patients. The
      patients were monitored daily for factor VIII (FVIII:C) and ristocetin cofactor
      (vWF: RCo) levels and the infusion rate was adjusted to maintain the desired
      therapeutic level of vWF:RCo. The treatment was effective in preventing surgical
      bleeding and controlling bleeding episodes. All factor VIII:C and most of the
      vWF:RCo levels measured during the study period were above the target therapeutic
      levels. A significant decrease in clearance of FVIII:C and vWF:RCo was observed
      over the treatment period. Haemate-P consumption averaged 24.3+/-7.9 vWF:RCo
      U/kg/day which is approximately half the expected dose had intermittent bolus
      injections been used. We suggest that continuous Haemate-P infusion is superior
      to intermittent bolus injections for the treatment of vWD patients by virtue of
      its efficiency, simplicity and considerable savings.

PMID- 10063998
TI  - Evaluation of an adenoviral vector encoding full-length human factor VIII in
      hemophiliac mice.
AB  - Adenoviral vectors provide a promising gene therapy system for the treatment of
      hemophilia A. Potent vectors encoding a human factor VIII (FVIII) cDNA were
      developed that mediated sustained FVIII expression in normal and hemophiliac mice
      and complete phenotypic correction of the bleeding disorder in hemophiliac mice
      and dogs (Connelly and Kaleko, Haemophilia 1998; 4: 380-8). However, these
      studies utilized vectors encoding a truncated version of the human FVIII cDNA
      lacking the B-domain (BDD FVIII). In this work, an adenoviral vector encoding the
      human full-length (FL) FVIII cDNA was generated and characterized. While
      functional FL FVIII was secreted in vitro, expression of the FL protein was not
      detected in the plasma of vector-treated hemophiliac mice. Unexpectedly, the FL
      FVIII vector-treated animals demonstrated phenotypic correction of the bleeding
      defect as measured by a tail-clip survival study. FL FVIII protein was visualized
      in the mouse livers using human FVIII-specific immunohistochemical analyses.
      These data demonstrate that adenoviral vector-mediated in vivo expression of BDD
      FVIII is more efficient than that of the FL protein and that phenotypic
      correction can occur in the absence of detectable levels of FVIII.

PMID- 10063999
TI  - Inhibitor antibody development and T cell response to human factor VIII in murine
      hemophilia A.
AB  - In order to understand better the mechanism of inhibitor formation in hemophilia
      A patients, we have characterized the immune response to human factor VIII in a
      murine model of hemophilia A. Mice with severe factor VIII deficiency caused by
      targeted gene disruptions in exons 16 and 17 were injected intravenously with
      human factor VIII. Anti-factor VIII was absent or was detected at only very low
      levels in hemophilic mice of both strains after a single injection of 0.2 microg
      factor VIII, but it was present in most mice after a second exposure. Subsequent
      exposures led to high titer anti-factor VIII antibodies in both ELISA and
      inhibitor assays. A human factor VIII-specific T cell proliferative response was
      detected with spleen cells obtained three days after a single injection with
      human factor VIII, before mice had detectable anti-factor VIII antibodies.
      Subsequent exposures to factor VIII were followed by an increased T cell
      proliferative response. These studies indicate that murine hemophilia A is a good
      model for the study of the immune response to human factor VIII, especially the
      role of the T cell in the early steps in inhibitor antibody formation.

PMID- 10064000
TI  - Recombinant factor VIIa does not induce hypercoagulability in vitro.
AB  - Recombinant factor VIIa (rVIIa) has been reported to be clinically effective and
      safe in haemophilic patients with inhibitor antibodies. Compared to activated
      prothrombin complex concentrates the risk of thrombotic complications seems to be
      very low after rVIIa administration. Determination of free thrombin generation
      has been shown to identify hypercoagulability. Therefore, free thrombin and
      prothrombinase activity (Xa generation) were assessed after extrinsic activation
      of rVIIa supplemented factor VIII and factor IX deficient plasma. Free thrombin
      generation was also determined after supplementation of (activated) prothrombin
      complex concentrates. Addition of 150 U rVIIa/ml shortened the clotting times
      markedly in control, factor VIII, and factor IX deficient plasma. In contrast,
      free thrombin and Xa generation were not different in the absence or presence of
      150 U rVIIa/ml. Addition of (activated) prothrombin complex concentrates resulted
      in a marked increase of free thrombin generation in all investigated plasmas.
      Although in vitro studies cannot reflect specific clinical circumstances our
      results support the notion that rVIIa does not induce a hypercoagulable state as
      sporadically observed after administration of (activated) prothrombin complex
      concentrates.

PMID- 10064001
TI  - Pharmacological effects of a novel recombinant hirudin, CX-397, in vivo and in
      vitro: comparison with recombinant hirudin variant-1, heparin, and argatroban.
AB  - The novel recombinant hirudin analog CX-397 was investigated with respect to its
      pharmacological activity and antithrombin profiles in vivo and in vitro. In three
      different types of thrombosis models in rats, including stasis and thrombin
      induced venous, glass surface-activated arterio-venous shunt, and ferric chloride
      induced arterial thrombosis models, CX-397 and rHV-1 elicited potent
      antithrombotic effects, where the minimum effective doses of rHV-1 tended to be
      higher than those of CX-397 in the arterio-venous shunt and arterial thrombosis
      models. The hemorrhagic risk of CX-397 in template bleeding in rats was not
      higher than that of rHV-1, indicating that CX-397 is superior to rHV-1 for
      treating the platelet-dominant type of thrombosis. However, no differences were
      detected between CX-397 and rHV-1 in their effects on in vitro coagulation times
      and thrombin-induced platelet aggregation, suggesting the possibility that some
      unknown mechanisms other than simple thrombin inhibition are also involved in
      their antithrombotic actions.

PMID- 10064002
TI  - dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant
      activity of anti-beta2-glycoprotein I autoantibodies.
AB  - Anti-beta2-glycoprotein I (beta2-GPI) antibodies behave as classical Lupus
      Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions
      and their activity disappears in the presence of excess exogenous phospholipids
      (PLs). We have recently shown that a certain amount of PLs in the dilute Russell
      Viper Venom Time (dRVVT) test system is required to express LA activity of anti
      beta2-GPI antibodies. We have now extended this observation to two other tests,
      i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue
      Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact,
      affinity-purified antibody preparations from 5 patients with antiphospholipid
      syndrome did not express or only weakly expressed anticoagulant activity in both
      tests; the mean ratios of coagulation times obtained with purified antibodies and
      that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the
      contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8
      and 1:64, respectively. Therefore, the presence of LA activity due to
      autoantibodies to beta2-GPI is characterized by a positive dRVVT and negative or
      only weakly positive KCT and TTI.

PMID- 10064003
TI  - Effects of diets enriched in lauric, palmitic or oleic acids on blood coagulation
      and fibrinolysis.
AB  - In this study we compared the effects of specific saturated fatty acids (lauric
      acid and palmitic acid) with those of a monounsaturated fatty acid (oleic acid)
      on coagulation and fibrinolytic parameters in healthy women and men. Eighteen
      women and fourteen men consumed, in random order, three experimental diets, each
      for six weeks. The diets consisted of solid foods and approximately 70% [28
      percent of energy (En%)] of the fat calories was supplied. As determined from
      duplicate portions, in the lauric acid diet 7.3 En% and in the palmitic acid diet
      6.1 En% of oleic acid were exchanged for lauric or palmitic acid, respectively.
      The lauric acid diet also contained some (average 1.8 En%) more myristic acid.
      Compared with the oleic acid diet, factor VIIam in the female subjects was 9%
      higher with the lauric acid diet (P = 0.0036; 95% CI, 3 to 14%) and 10% higher
      with the palmitic acid diet (P = 0.0011; 95% CI, 5 to 16%). Changes in men were
      not significant. Plasminogen Activator Inhibitor (PAI-1) activity was higher on
      the palmitic acid compared with the oleic acid diet (difference between diets of
      2.3 U/ml; P = 0.0098; 95% CI, 0.4 to 4.3 U/ml) and the lauric acid diet
      (difference between diets of 2.2 U/ml; P = 0.0123; 95% CI, 0.2 to 4.1 U/ml). No
      significant differences between diets were observed for antithrombin III
      activity, fibrinogen concentrations, fragment 1+2 concentrations, plasminogen or
      alpha2-antiplasmin activity. From this study, we conclude that diets rich in
      lauric or palmitic acid, compared with a diet rich in oleic acid, unfavourably
      influence factor VIIam activity, in a gender specific manner. In addition, the
      plasminogen activator inhibiting capacity of the plasma is impaired with a
      palmitic acid rich diet compared with an oleic or lauric acid rich diet.

PMID- 10064004
TI  - A 96-well microfiltration assay for measurement of total clottable fibrinogen.
AB  - In clinical routine use, fibrinogen is measured by clotting-time methods, or by
      clot turbidity in photometric prothrombin time determination. For calibration of
      these assays measurement of total thrombin-clottable protein has been
      recommended. We have now developed a microfiltration assay for total thrombin
      clottable protein. Plasma samples were mixed with thrombin in a 96-well
      microfiltration device. After clot formation, the fluid was extracted by vacuum
      suction, and fibrin adherent to the filter membranes washed with buffer. Membrane
      segments with adherent fibrin were recovered from the 96-well manifold with a
      punch and transferred to tubes containing denaturing buffer solution. After
      dissolution of fibrin, protein concentration was determined by optical absorption
      at 280 nm. The microfiltration assay displayed a high correlation with the total
      clottable protein method (R = 0.95), and fibrinogen antigen (r = 0.96).
      Correlation with clotting time assays, and PT-derived fibrinogen in 150 clinical
      plasma samples was in the range of r = 0.84 to r = 0.97. Intraassay and day-to
      day variability of the assay was comparable to the conventional total clottable
      fibrinogen assay. The novel microfiltration assay appears to be well suited for
      measurement of large series of samples for calibration, screening purposes, and
      clinical trials.

PMID- 10064005
TI  - Fibrinogen St. Gallen I (gamma 292 Gly--> Val): evidence for structural
      alterations causing defective polymerization and fibrinogenolysis.
AB  - Fibrinogen St. Gallen I was detected in an asymptomatic Swiss woman. Routine
      coagulation tests revealed a prolonged thrombin and reptilase time. Functionally
      measured fibrinogen levels were considerably lower than those determined
      immunologically. Polymerization of fibrin monomers derived from purified
      fibrinogen was delayed in the presence of either calcium or EDTA. Normal
      fibrinopeptide A and B release by thrombin was established. An abnormal
      degradation of fibrinogen St. Gallen I by plasmin was observed. Fragment D1 of
      normal fibrinogen was fully protected against further proteolysis in the presence
      of 10 mM calcium, whereas fibrinogen St. Gallen I was partially further degraded
      to fragments D2 and D3. In the presence of 10 mM EDTA, the conversion of variant
      fragment D1 to D2 was accelerated whereas the degradation of fragment D2 to D3
      was delayed in comparison to degradation of fragments D1 and D2 of normal
      fibrinogen. Three high-affinity calcium binding sites were found in both normal
      and variant fibrinogen. Mutation screening with SSCP analysis suggested a
      mutation in exon VIII of the gamma-chain gene. Cycle sequencing of this gene
      portion revealed a single base substitution from G to T of the base 7527, leading
      to replacement of gamma 292 glycine by valine. The same mutation has already been
      described for the fibrinogen variant Baltimore I. Molecular modeling was
      performed of a part of the gamma-chain containing the mutation site, based on
      recently published X-ray crystal structures of human fibrinogen fragment D and of
      a 30 kD C-terminal part of the gamma-chain. Significant structural alterations
      due to the substitution of glycine by valine at gamma 292 were observed, e.g.
      spreading of the protein backbone, probably leading to a modified accessibility
      of the plasmic cleavage sites in the gamma-chain at 356 Lys and 302 Lys. A shift
      of gamma 297 Asp that is involved in interactions of fragment D with the Gly-Pro
      Arg-Pro-peptide was noted by molecular modeling. The latter observation is
      compatible with delayed polymerization of fibrin monomers.

PMID- 10064006
TI  - Fibrinolytic activity in peripheral atherosclerosis in the elderly.
AB  - Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of
      D-dimer have jointly been found in subjects with cardiovascular disease. To
      understand this apparent paradox of increased inhibition of fibrinolysis (high
      PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined
      the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue
      type plasminogen activator (t-PA) in subjects with varying severity of peripheral
      atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of
      7983 men and women aged 55 years and over, the ankle to brachial systolic blood
      pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were
      measured. T-PA antigen and t-PA activity were, independent from each other,
      increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml
      (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit
      decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis).
      PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was
      associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below
      50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In
      contrast to current beliefs, we found that only a fraction of the variation of t
      PA antigen was due to the variation in circulating PAI-1 antigen. A slight
      positive association was observed between t-PA antigen and D-dimer. PAI-1 and t
      PA activity were not associated with D-dimer concentration. In conclusion, in
      subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low
      PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t
      PA activity) appear to be required to increase circulating D-dimer. This suggests
      that increased D-dimer levels in subjects with atherosclerosis do not reflect
      increased inhibition, but rather reflect increased fibrinolysis.

PMID- 10064007
TI  - Modulation of platelet-neutrophil interaction with pharmacological inhibition of
      fibrinogen binding to platelet GPIIb/IIIa receptor.
AB  - The study investigated how drug inhibition of the GPIIb/IIIa receptor influences
      the interactions between platelets and leukocytes. These interactions are
      believed to play an important role in the etiology of the acute coronary
      syndromes. Thirty patients with unstable angina or non-Q-wave myocardial
      infarction were studied before the administration of tirofiban or placebo and
      after 4 h and 72 h. Platelet-leukocyte aggregates were characterized in whole
      blood using three-colour flow cytometry. The leukocyte population was isolated by
      a nucleic acid probe (LDS 751) and platelet-neutrophil coaggregates identified as
      particles binding both anti-CD42a-FITC and anti-CD45-PE. Tirofiban decreased by
      25% the density of platelets in circulating platelet-neutrophil coaggregates (p
      <0.01), and prevented the increase induced by platelet agonist stimulation (p
      <0.0001). The reduction correlated with inhibition of fibrinogen binding to
      platelet (p <0.0001) and with inhibition of platelet aggregation (p <0.0001). The
      percentage of neutrophils with bound platelets following platelet agonist
      stimulation was, however, increased following GPIIb/IIIa inhibition. Thus,
      inhibition of GPIIb/IIIa receptor promotes platelet-neutrophil adhesion, but
      markedly reduces the binding density of platelets in the coaggregates.

PMID- 10064008
TI  - Secreted dense granule adenine nucleotides promote calcium influx and the
      maintenance of elevated cytosolic calcium levels in stimulated human platelets.
AB  - Evidence that secreted dense granule adenine nucleotides mediate part of the
      agonist-induced cytosolic calcium ([Ca2+]i) responses in human platelets was
      obtained from comparisons of fura-2-loaded platelets from normal subjects and
      from patients with a form of platelet storage pool deficiency (SPD) in which the
      secretory dense granules and their contents are virtually absent. SPD platelets
      had normal initial [Ca2+]i increases induced by thrombin and the endoperoxide
      analog U46619, but a significantly enhanced decay of elevated [Ca2+]i levels
      following the initial increases. With thrombin, this enhanced [Ca2+]i decay was
      associated with decreased Ca2+ influx, as measured by Mn2+ quench of fura-2
      fluorescence. Addition of micromolar concentrations of ADP, alone or together
      with ATP, after stimulation reversed the enhanced [Ca2+]i decay and increased
      Mn2+ quench in SPD platelets, but had no effect on these responses in normal
      platelets, while addition of 100-fold higher concentrations of ATP or apyrase
      before stimulation increased [Ca2+]i decay and decreased Mn2+ quench in normal
      platelets, but had little effect in SPD platelets. ATP and alpha,beta-methylene
      ATP, a specific agonist for P2X1 receptors, at micromolar concentrations also
      increased Mn2+ quench, but to lesser extents than did ADP, in SPD platelets
      isolated and loaded with fura-2 in the presence of apyrase. Similar effects of
      ADP and excess ATP were seen in U46619-stimulated platelets, but decreased Ca2+
      influx could not be measured directly in SPD platelets, presumably due to the
      very transient influx response seen with U46619. These results suggest that
      secreted dense granule ADP and ATP contribute to the maintenance of elevated
      [Ca2+]i levels, but not to the initial [Ca2+]i increases, in stimulated human
      platelets, most likely via a nucleotide-specific component of Ca2+ influx which
      may be mediated by interactions with both P2X1 and P2Y1 purinoceptors.

PMID- 10064009
TI  - Effect of pulse pressure on vascular smooth muscle cell migration: the role of
      urokinase and matrix metalloproteinase.
AB  - Plasminogen activator (PA) expression plays an important role in smooth muscle
      cell (SMC) migration and may therefore contribute to mechanical force-induced
      arterialization of vein grafts. The aim of this study was to determine whether
      pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)
      dependent mechanisms. Using a perfused transcapillary culture system, human
      umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or
      presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow
      rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their
      migration following exposure to increased pulse pressure (248+/-14%). Both u-PA
      and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in
      SMC exposed to pressure as compared to static controls. The role of proteases in
      the pulse pressure-induced enhancement of SMC migration was confirmed following
      pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase
      inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti
      u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7%
      for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out
      mice, the SMC migratory response to increased pulse pressure was completely
      inhibited despite a significant increase in MMP expression in these cells. These
      results suggest that pulse pressure due to pulsatile flow induces SMC migration
      in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion
      results in blunting of pressure-induced SMC migration despite the endogenous
      upregulation of metalloproteinase. Modulation of u-PA expression by pressure may
      thus represent an important mechanism whereby hemodynamic forces regulate smooth
      muscle cell migration.

PMID- 10064010
TI  - Profile of recombinant pro-urokinase given by intraarterial versus intravenous
      routes of administration in a canine thrombosis model.
AB  - Catheter-directed thrombolysis has gained increasing acceptance for the treatment
      of patients who present with vascular occlusion; however, intravenous injection
      may be preferable in selected patients. Recombinant prourokinase (r-proUK) is a
      recently-developed fibrin-selective thrombolytic agent with specificity for clot
      bound plasminogen. To compare the effects of r-proUK on clot lysis and
      restoration of blood flow when injected by either intraarterial or intravenous
      routes of administration, we utilized a dog model of arterial thrombosis in which
      a radiolabelled clot is formed in the femoral artery. The r-proUK was given by
      intravenous infusion to one group of 18 animals in doses ranging from 10,000
      IU/kg to 100,000 IU/kg; a second group of 27 dogs was treated with r-proUK
      administered by the intra-arterial route in a dose range from 300 IU to 10,000
      IU. Clot lysis was measured by monitoring the loss of counts from the
      radiolabelled clot over time; blood flow was also monitored throughout the
      experimental period. Animals which received intravenous treatment showed dose
      related clot lysis ranging from 14% to 70% at 2 h, while those which received
      intra-arterial infusions showed lysis ranging from 22% to 79% over the same
      period. For similar degrees of clot lysis attained at the highest dose levels of
      100,000 IU/kg and 10,000 IU, blood flow was restored to 77% and 35% of control
      levels in dogs which received intravenous and intraarterial treatment,
      respectively. The hemostatic protein fibrinogen was not reduced in any of the
      treatment groups. The results indicate that 100 times more intravenous than intra
      arterial r-proUK is required to produce similar clot lysis in this canine model,
      and that the agent can be administered at this level without induction of a
      systemic lytic state.

PMID- 10064011
TI  - A new animal model of thrombophilia confirms that high plasma factor VIII levels
      are thrombogenic.
AB  - The thrombotic risk associated with elevated plasma levels of clotting factor
      VIII (FVIII) was investigated in a mouse model of thrombophilia. After the
      intravenous injection of recombinant human FVIII and/or of purified FVIII-free
      human von Willebrand factor (vWF), a controlled mild injury was inflicted on the
      carotid artery of FVB mice by irradiation with filtered green light in
      combination with intravenous injection of the dye rose bengal. Formation of a
      platelet-rich thrombus was continuously monitored for 40 min via
      transillumination and the thrombus size was measured via image analysis.
      Administration of recombinant human FVIII at 40 microg/kg led to initial FVIII
      plasma activities equivalent to 250% of normal human plasma FVIII activity and
      significantly enhanced thrombus size. Immunohistochemical staining illustrated
      the accumulation of FVIII within the thrombi. Human vWF, even at 10 mg/kg, had no
      effect on thrombus formation. The thrombotic tendency induced by FVIII was
      significantly inhibited by the administration of human vWF in a dose-dependent
      manner. Separate plasma measurements revealed that human FVIII has comparable
      affinities for human and murine vWF but that human vWF does not effectively bind
      murine platelets. The inhibition by human vWF of the thrombotic tendency induced
      by human FVIII could therefore be explained by a lack of accumulation of FVIII
      within the developing thrombus because of the reduced affinity of human vWF for
      murine platelets and the reduced occupancy of murine von Willebrand factor by
      human FVIII after injection of human vWF. These results show that vWF actively
      participates in FVIII accumulation in the arterial thrombus and provide
      experimental evidence for epidemiological findings that elevated plasma FVIII
      levels are associated with an increased thrombotic risk, also in arteries.

PMID- 10064012
TI  - The prevalence of factor V Arg306-->Thr (factor V Cambridge) and factor V Arg306-
      >Gly mutations in different human populations.

PMID- 10064013
TI  - Multiplex PCR for one-step determination of the G20210A variation and the factor
      V Leiden mutation by denaturing gradient gel electrophoresis (DGGE)

PMID- 10064014
TI  - The relations of major platelet receptor expression during myocardial infarction.
      Monitoring efficacy of GPIIb/IIIa inhibitors by measuring P-selectin?

PMID- 10064015
TI  - Binding of heparin to platelet membrane glycoprotein Ib: functional effects.

PMID- 10064016
TI  - Acquired hypoprothrombinemia related to high titres of antiprotein-phospholipid
      antibodies.

PMID- 10064017
TI  - IgA antiphospholipid antibodies.

PMID- 10064018
TI  - A new automated method for von Willebrand factor antigen measurement using latex
      particles.

PMID- 10064019
TI  - Assessment of the expression of candidate human plasma membrane phospholipid
      scramblase in Scott syndrome cells.

PMID- 10064020
TI  - Treatment of hirudin overdosage in a patient with chronic renal failure.

PMID- 10064021
TI  - Evaluation of life-cycle herd efficiency in cow-calf systems of beef production.
AB  - A deterministic beef efficiency model (BEM) was used to evaluate life-cycle herd
      efficiency (LCHE) in cow-calf beef production systems using four breed groups of
      beef cattle. The breed groups were Beef Synthetic #1 (SY1), Beef Synthetic #2
      (SY2), Dairy Synthetic (DS), and purebred Hereford (HE). The LCHE was defined
      over the lifetime of the herd as the ratio of total output (lean meat equivalent)
      to total input (feed equivalent). Breed differences in LCHE were predicted with
      the larger/slower maturing DS being most efficient at each age of herd disposal
      and reproductive rate. This was mainly because, at any average age at culling,
      the dams of DS breed group were less mature and so had been carrying relatively
      lower maintenance loads for shorter periods and positively influencing LCHE.
      Higher LCHE was predicted with improvement in reproductive performance if there
      were no associated extra costs. However, this declined markedly if there was a
      delay in marketing of offspring. As average age at culling increased from 4 to 6
      yr, efficiency declined sharply, but it began to recover beyond this age in most
      breed groups. We concluded that the slower maturing DS breed group may be more
      efficient on a herd basis in cow-calf systems and that improvements in
      reproductive rate not associated with extra costs improve life-cycle efficiency.
      Culling cows soon after their replacements are produced seems efficient.

PMID- 10064022
TI  - Gonadotropin-releasing hormone improves reproductive performance of dairy cows
      with slow involution of the reproductive tract.
AB  - Eighty multiparous Holstein cows were assigned randomly at calving to receive
      either 100 microg of GnRH or saline 13 or 14 d postpartum (PP). From 4 to 28 d PP
      the cows' reproductive organs were palpated weekly per rectum, and cows were
      subclassified within each group as undergoing slow (delayed) cervical and uterine
      involution (abnormal) or as normal cows. Last milk obtained after removing the
      milking machine was assayed for progesterone 3 times a week for 120 d PP.
      Fourteen of the 80 cows were removed from the experiment because of culling or
      various veterinary treatments of pathologic conditions that could confound
      analysis of the GnRH treatment effects. As expected, the treatment of normal cows
      with GnRH had no significant effects on the first estrus or the first estrous
      cycle PP, on services per conception, days open, or any other reproductive trait
      measured. However, in the abnormal group of cows receiving saline, first
      rebreeding after calving was delayed (81 vs. 67 d), fewer were pregnant by 105 d
      PP (23 vs. 64%), and number of days open was greater (121 vs. 87 d) compared with
      those receiving GnRH; all were significant (P<.05). Treated abnormal cows were
      equivalent to the control normal cows. Thus, GnRH given 13 to 14 d PP to cows
      characterized as undergoing slow involution of the reproductive system, but with
      no other clinical problems, seems to assist in promoting rapid normal
      reproductive function. Subsequent losses due to culling were greatly reduced.

PMID- 10064023
TI  - The effect of bovine somatotropin treatment on production of lactating angora
      does with kids.
AB  - Fourteen Angora does (35+/-2 kg), each with a single kid and in the first month
      of lactation, were used to determine ongoing (Period 1) and residual (Period 2)
      effects of chronic bovine somatotropin (bST) treatment. Specifically, we sought
      to determine whether chronic bST treatment was capable of improving milk yield,
      and thus kid growth, and mohair production of nursing does. The experiment
      consisted of a 2-wk pretreatment period, 5 wk of weekly subcutaneous treatment of
      slow-release bST (n = 7; Period 1), and a 4-wk posttreatment period (Period 2).
      The weekly dose of bST was calculated to release 100 microg/(kg BW.d(-1)). To
      estimate milk production, kids were separated from the does daily for 5 h, and
      their BW was recorded before and after suckling. The difference in BW was taken
      as milk production for 5 h. Fiber growth was measured by shearing does at the
      start of the experiment and at the end of Periods 1 and 2. Dry matter intake and
      BW of does were not affected by bST (P>.05). Average daily gain of kids that were
      suckling bST-treated does was higher (P<.05) than for kids of untreated does
      during Period 1 (184 vs. 139 g/d) but not during Period 2 (140 vs. 136 g/d;
      P>.10). Treatment with bST did not affect (P>.10) milk composition or clean
      fleece production in either period. Injection of bST did not affect (P>.10)
      plasma concentrations of glucose (mean = 49.5 mg/dL), urea N (mean = 19 mg/dL),
      total protein (mean = 72.5 g/d), or NEFA (mean = 122 microEq/L). During the
      period of bST treatment, plasma concentrations of somatotropin and IGF-I were
      increased (P<.05), concentrations of thyroxine and cortisol were decreased
      (P<.10), and plasma insulin levels were unchanged (P>.10) by bST. In conclusion,
      treatment of Angora dams with bST did not change DMI or mohair growth, but it
      improved growth of their kids.

PMID- 10064024
TI  - Postweaning performance of calves from Angus, Brahman, and reciprocal-cross cows
      grazing endophyte-infected tall fescue or common bermudagrass.
AB  - Data from 403 Polled Hereford-sired calves from Angus, Brahman, and reciprocal
      cross cows were used to evaluate the effects of preweaning forage environment on
      postweaning performance. Calves were spring-born in 1991 to 1994 and managed on
      either endophyte-infected tall fescue (E+) or common bermudagrass (BG) during the
      preweaning phase. After weaning, calves were shipped to the Grazinglands Research
      Laboratory, El Reno, OK and stratified to one of two winter stocker treatments by
      breed and preweaning forage; stocker treatments were winter wheat pasture (WW) or
      native range plus supplemental CP (NR). Each stocker treatment was terminated in
      March, calves grazed cool-season grasses, and calves were then moved to a feedlot
      phase in June. In the feedlot phase, calves were fed to approximately 10 mm fat
      over the 12th rib and averaged approximately 115 d on feed. When finished, calves
      were weighed and shipped to Amarillo, TX for slaughter. Averaged over calf breed
      group, calves from E+ gained faster during the stocker phase (P<.10), had lighter
      starting and finished weights on feed (P< .01), lighter carcass weights (P<.01),
      and smaller longissimus muscle areas (P<.05) than calves from BG. Calves from E+
      were similar to calves from BG in feedlot ADG, percentage kidney, heart, and
      pelvic fat, fat thickness over 12th rib, yield grade, marbling score, and
      dressing percentage. Maternal heterosis was larger in calves from E+ for starting
      weight on feed (P<.01), finished weight (P<.10), and carcass weight (P<.16).
      These data suggest that few carryover effects from tall fescue preweaning
      environments exist, other than lighter, but acceptable, weights through
      slaughter. These data further suggest that the tolerance to E+ in calves from
      reciprocal-cross cows, expressed in weaning weights, moderated postweaning weight
      differences between E+ and BG compared to similar comparisons in calves from
      purebred cows.

PMID- 10064025
TI  - Pregnancy detection and the effects of age, body weight, and previous
      reproductive performance on pregnancy status and weaning rates of farmed fallow
      deer (Dama dama).
AB  - Fallow does (n = 502) of different ages (mature, 2-yr-old, and yearling) were
      maintained with bucks for a 60-d breeding season to determine whether previous
      reproductive performance and changes in BW affect doe pregnancy rates and to
      compare the effectiveness of ultrasonography and serum pregnancy-specific protein
      B (PSPB) for the detection of pregnancy in fallow does. Ultrasonography was
      performed, blood samples collected, and BW recorded at buck removal (d 0) and at
      30 and 90 d after buck removal. Lactational status (lactating = WET; nonlactating
      = DRY) were determined from farm records taken at weaning prior to each breeding
      season (autumn 1990 through autumn 1994). Ultrasonography and PSPB for
      determining pregnancy were in agreement 93% of the time. Overall pregnancy rates
      did not differ (P>.10) relative to age of the doe; the combined pregnancy rate
      was 92%. We also determined that 82.9% of does conceived early in the breeding
      season and that the incidence of embryonal-fetal mortality during the first 90 d
      after buck removal was 2.8%. In general, mature and 2-yr-old DRY does were
      heavier and had lower pregnancy rates than WET does. The overall weaning rate for
      all does was 77.9%. Loss in the number of fawns from pregnancy detection to
      weaning was equivalent to 14.8% for mature does, 24.7% for 2 yr old does, and
      42.5% for yearling does. These data indicate that even though pregnancy rates
      were relatively high, further study is needed to determine the causes associated
      with subsequent fawn losses, particularly among yearling does. As a production
      tool, lactational WET/ DRY status testing was found to be an acceptable means for
      determining the reproductive potential of individual does within the herd. In
      addition, serum PSPB may be used in place of ultrasonography for pregnancy
      diagnosis in fallow deer as early as d 30 after buck removal.

PMID- 10064026
TI  - Effects of twinning on gestation length, retained placenta, and dystocia.
AB  - Constraints to maximal productivity from twinning in beef cattle include
      increased incidence of dystocia and retained placenta, longer postpartum
      interval, and lower conception rate. Incidence and cause(s) of the shorter
      gestation length and of the increased retained placenta and dystocia associated
      with twinning were evaluated for 3,370 single and 1,014 twin births produced in a
      population of cattle selected for natural twin births. Gestation length was
      shorter for twin than for single pregnancies (275.6 vs. 281.3 d, P<.01) and
      likely contributed to the higher incidence of retained placenta associated with
      twin births (27.9 vs. 1.9%; P<.01). Incidence of retained placenta was also
      higher in the spring (March-April) than in the fall (August-September) calving
      season (18.3 vs. 11.4%; P<.01). The higher incidence of dystocia with twins than
      with singles (46.9 vs. 20.6%, P<.01) was primarily due to abnormal presentation
      (37.0 vs. 4.5%, respectively) of one or both twin calves at parturition. First-
      (40.5%) and second- (22.7%) parity dams with a single birth had more (P<.01)
      dystocia than older dams (13.4%), whereas dystocia was not affected (P>.10) by
      parity with twin births. Because of the shorter gestation length and the
      increased incidence of retained placenta and(or) dystocia, achievement of
      increased productivity with twinning in cattle necessitates intensive management
      of twin-producing dams and their calves during the calving season. Management of
      the increased dystocia can be facilitated by preparturient diagnosis of twin
      pregnancies, enabling timely administration of obstetrical assistance to
      facilitate delivery of twin calves and to increase their neonatal survival.

PMID- 10064027
TI  - Effects of twinning on postpartum reproductive performance in cattle selected for
      twin births.
AB  - The effects of twinning, dystocia, retained placenta, and body weight on
      postpartum reproduction were evaluated for 3,370 single and 1,014 twin births.
      Females were bred by AI for 40 d followed by 20 or 30 d of natural service with
      equal numbers bred and calved in spring and fall. Percentage of dams cyclic by
      the end of the AI period was lower (P<.05) for dams birthing and nursing a single
      calf (92.4%) than for dams birthing twins and nursing zero (98.7%) or two (94.7%)
      calves. Whereas the interval from parturition to first estrus was shorter (P<.01)
      for dams birthing and nursing a single (56.9 d) than for dams birthing twins and
      nursing one (68.5 d) or two (69.6 d) calves, length of the interval was further
      reduced by dystocia in nonlactating dams of either twins or singles (type of
      birth x dystocia, P<.05). Ensuing pregnancy rates were also affected by type of
      birth and dystocia. Without dystocia, dams birthing and nursing a single calf had
      a higher pregnancy rate (79.2%) than dams birthing twins and nursing one (61.7%)
      or two (66.3%) calves, whereas the lower ensuing pregnancy rates associated with
      dystocia in dams of singles (71.9%) resulted in similar rates among dams of
      singles and twins with dystocia (type of birth x dystocia; P<.01). Having a
      retained placenta resulted in a lower incidence of (93.5 vs. 96.4%, with vs.
      without; P<.05) and a longer interval to (64.7 vs. 59.2 d; P<.01) estrus while
      reducing subsequent pregnancy rates (X = 9.6%) in 3 of the 7 yr evaluated
      (retained placenta x year, P<.01). Because all parous females were bred during
      the same calendrical period, the shorter gestation length for twin calves (275.6
      vs. 281.3 d) resulted in a longer interval from parturition to conception for
      twin births, whereas means for conception date differed by only 2 d between dams
      of twins and singles. Furthermore, a reduction (P<.01) in the interval to
      conception occurred with dystocia in dams of singles (89.3 vs. 85.0 d, without
      vs. with dystocia) and of twins nursed by zero (116.9 vs. 83.5 d), one (100.2 vs.
      92.8 d), or two (96.1 vs. 97.2 d) calves. Another detriment to fertility was the
      higher incidence of fetal mortality or abortions associated with twin vs. single
      pregnancies (12.4 vs. 3.5%; P<.01). However, despite the lower conception rates
      for dams of twins, the increased prolificacy provides an opportunity to increase
      total beef production with a twinning technology.

PMID- 10064028
TI  - The importance of genetic diversity in livestock populations of the future.
AB  - Farm animal genetic diversity is required to meet current production needs in
      various environments, to allow sustained genetic improvement, and to facilitate
      rapid adaptation to changing breeding objectives. Production efficiency in
      pastoral species is closely tied to the use of diverse genetic types, but greater
      genetic uniformity has evolved in intensively raised species. In poultry,
      breeding decisions are directed by a few multinational companies and involve
      intense selection, the use of distinct production lines, and very large
      populations. In dairy cattle, the Holstein breed dominates production. Intensive
      sire selection is leading to relatively rapid inbreeding rates and raises
      questions about long-term effects of genetic drift. Key questions in management
      of farm animal genetic diversity involve the distribution of potentially useful
      quantitative trait locus alleles among global livestock breeds. Experiments with
      tomato, maize, and mice suggest that favorable alleles can exist in otherwise
      lowly productive stocks; this cryptic variation may potentially contribute to
      future selection response. Genetic improvement under relatively intense
      unidirectional selection may involve both increases in the frequency of favorable
      additive alleles as well as the progressive breakdown of homeostatic regulatory
      mechanisms established under the stabilizing selection that is characteristic of
      natural populations. Recombination among closely linked regulatory loci and new,
      potentially favorable mutations are possible sources of long-term genetic
      variation. A greater understanding of the potential that these alternative
      mechanisms have for supporting long-term genetic improvement and of genetic
      relationships among global livestock populations are priorities for managing farm
      animal genetic diversity.

PMID- 10064029
TI  - The effect of age and teat order on alpha1-acid glycoprotein, neutrophil-to
      lymphocyte ratio, cortisol, and average daily gain in commercial growing pigs.
AB  - The objectives of the study were to evaluate age and teat order on a performance
      trait, average daily gain, and on physiological stress indicators, alpha1-acid
      glycoprotein (AGP), neutrophil-to-lymphocyte ratio (N:L), and cortisol in
      commercial growing pigs from weaning to market age. Pigs (n = 129) from five
      commercial California farms were weighed and blood-sampled at 28-d intervals from
      28 to 168 d of age. Laboratory assays were performed from blood samples to
      quantify cortisol, AGP, and N:L. Age and facility effects (P<.001), but not teat
      order effects (P>.05), were found for all three physiological traits and ADG.
      Pigs that routinely suckled from teats 1, 4, or 6 (numbered from anterior to
      posterior on the upper teat bank) had similar (P>.05) ADG and BW throughout the
      production cycle. No correlation (P> .05) was found between cortisol, AGP, and
      N:L. The use of these physiological and production traits as stress and health
      indices of growing pigs in commercial facilities has limitations in comparing
      data between facilities or different ages of pigs.

PMID- 10064030
TI  - Diurnal variation and age differences in the biochemical markers of bone turnover
      in horses.
AB  - Biochemical markers of bone turnover provide sensitive, rapid, and noninvasive
      monitoring of bone resorption and formation. Serum concentrations of osteocalcin
      (OC) reflect rates of bone formation, and urinary concentrations of the
      pyridinium crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpd) are specific
      and sensitive markers of bone resorption. These markers are age-dependent and are
      used to detect and monitor changes in the rates of bone turnover in a variety of
      orthopedic diseases in humans and may prove to have similar application in
      horses. This study examined age differences and diurnal variation in OC, Pyd, and
      Dpd in eight adult geldings and seven weanling colts. Blood and urine were
      collected at regular intervals over 24 h. Serum OC and cortisol, and urinary Pyd
      and Dpd were analyzed. Mean 24-h concentrations of cortisol and all three markers
      were higher (P<.003) in weanlings than adults. Significant 24-h variation was
      observed in adult gelding OC, Pyd, and Dpd concentrations (P< .02). Adult OC
      concentrations were highest between 2400 and 0900; Pyd and Dpd peaked between
      0200 and 0800. Similar patterns of bone turnover were observed in weanling
      values, but they were not significant (P>.17) owing to greater variability
      between individuals. Cortisol secretion varied (P<.001) over 24 h in both adults
      and weanlings and, thus, did not seem to be responsible for greater variability
      in markers of bone turnover between weanlings. These data demonstrate that
      diurnal rhythms exist for serum OC and urinary Pyd and Dpd in adult horses, as
      reported in humans, and that sample timing is an important consideration in
      future equine studies using these markers.

PMID- 10064031
TI  - Relationship between metabolism of androstenone and skatole in intact male pigs.
AB  - The relationship between the metabolism of androsterone and skatole, the major
      compounds responsible for boar taint, was investigated in F4 Swedish Yorkshire x
      European Wild Pig intact males. The metabolism of androstenone and skatole were
      studied in liver microsomes, and the testicular steroid production was measured
      in testes microsomes. Including androstenone in the assays of skatole metabolism
      reduced the formation of 6-hydroxyskatole (pro-MII), and three other skatole
      metabolites (P<.05). The formation of three additional metabolites was not
      affected. Liver microsomal incubations of androstenone produced two metabolites,
      I and II. The rate of the formation of metabolite I and the rate of androstenone
      metabolism were correlated with the rate of skatole metabolism. Liver metabolism
      of androstenone was not related to levels of androstenone in fat. Testicular
      synthesis of 16-androstene steroids was correlated with combined synthesis of
      estrogens and androgens, plasma levels of androstenone, levels of skatole in fat,
      and skatole metabolism in the liver (P<.05). Plasma levels of estrone sulfate
      were correlated with levels of skatole in fat and with androstenone levels in fat
      and plasma and were negatively correlated with synthesis of skatole metabolite F
      1 and pro-MII sulfation. These results indicate that the liver metabolism of
      androstenone and skatole are related. However, it is likely that the relationship
      between levels of androstenone and skatole in fat is due more to a link between
      the testicular synthesis of androstenone rather than to the metabolism of
      androstenone and skatole in the liver. Sex steroids may affect this relationship
      because of their biosynthesis along with androstenone and possible inhibition of
      skatole metabolism in the liver.

PMID- 10064032
TI  - Structural changes in intramuscular connective tissue during the fattening of
      Japanese black cattle: effect of marbling on beef tenderization.
AB  - We investigated changes in structures and mechanical properties of the
      intramuscular connective tissue during the fattening of Japanese Black steers,
      using the cell maceration method for scanning electron microscopy. During the
      early fattening period, from 9 to 20 mo of age, collagen fibrils of the
      endomysium in longissimus muscle associated more closely with each other, and
      collagen fibers in the perimysium increased in thickness and their wavy pattern
      became more regular. These changes were closely related to the increase in
      mechanical strength of the intramuscular connective tissue and resulted in a
      toughening of the beef during the period. The shear force value of longissimus
      muscle decreased after 20 mo of age, concomitantly with the rapid increase in the
      crude fat content. Scanning electron micrographs of the longissimus muscle
      dissected from 32-mo-old steers clearly showed that the adipose tissues were
      formed between muscle fiber bundles, that the honeycomb structure of endomysia
      was partially broken, and that the perimysium separated into thinner collagen
      fibers. In semitendinosus muscle, in which the crude fat content was lower
      (P<.05) than that in longissimus muscle, the structure of the intramuscular
      connective tissue remained rigid at 32 mo of age. The shear force value of the
      muscle increased even in the late fattening period, from 20 to 32 mo of age.
      Thus, the development of adipose tissues in longissimus muscle appears to
      disorganize the structure of the intramuscular connective tissue and contributes
      to tenderization of highly marbled beef from Japanese Black cattle during the
      late fattening period.

PMID- 10064033
TI  - Antioxidative and oxidative status in muscles of pigs fed rapeseed oil, vitamin
      E, and copper.
AB  - The susceptibility of a given muscle tissue to lipid oxidation may not only
      depend on the presence of unsaturated fatty acids and the balance between
      antioxidants and prooxidants, but also on the composition of the skeletal muscle.
      In the present study, the effects of dietary supplementation of vitamin E (dl
      alpha-tocopheryl acetate) and copper in combination with a high level of
      monounsaturated fatty acids were examined with regard to the antioxidant
      concentration and the susceptibility to lipid oxidation of two muscles,
      longissimus (LD) and psoas major (PM), representing different oxidative capacity.
      In addition, fatty acid profiles of the backfat and the intramuscular lipids, as
      well as fresh meat quality traits, were studied. Pigs were allotted to a 3x3
      factorial experiment with three levels of dl-alpha-tocopheryl acetate (0, 100,
      and 200 mg/kg of feed) and three levels of copper (0, 35, and 175 mg/kg of feed)
      added to a diet containing 6% rapeseed oil. A basal diet (without rapeseed oil)
      was added to the experimental design, giving a total of 10 dietary treatments.
      Muscle alpha-tocopherol concentrations increased (P<.001) with increasing dl
      alpha-tocopheryl acetate in the feed. The antioxidative status was higher in PM
      than in LD, when considering the concentration of alpha-tocopherol (P<.001) and
      the activity of antioxidant enzymes (superoxide dismutase, P<.001; glutathione
      peroxidase, P = .06). Supplemental copper did not give rise to any deposition of
      copper in muscle tissue or backfat, but the antioxidant status of PM increased.
      The susceptibility to lipid oxidation was reduced in LD with increasing dietary
      dl-alpha-tocopheryl acetate and in PM with increasing dietary copper.
      Supplemental dl-alpha-tocopherol acetate improved the water-holding capacity of
      LD (P = .005) and PM (P = .003). The fatty acid composition of the backfat and
      the triglyceride fraction of the intramuscular fat became more unsaturated with
      the addition of rapeseed oil to the feed. Higher intakes of monounsaturated fatty
      acids due to the rapeseed oil were also reflected in the phospholipid fraction of
      the intramuscular fat, but no influence on the proportion of saturated fatty
      acids was seen. The susceptibility to lipid oxidation of PM was lower for pigs on
      the rapeseed oil-based diet than for those on the basal diet. The energy
      metabolic status of the muscles and the accumulation of calcium by the
      sarcoplasmic reticulum were not influenced by the dietary treatments, but there
      were differences between muscle types. The addition of rapeseed oil to the diet
      reduced the muscular content of glycogen (LD, P = .02; PM, P = .06) and elevated
      the plasma concentration of free fatty acids (P = .05). Overall, dietary fat, dl
      alpha-tocopherol acetate, and copper affected the oxidative status of pig
      muscles, and the results differed depending on muscle type.

PMID- 10064034
TI  - Accuracy of application of USDA beef quality and yield grades using the
      traditional system and the proposed seven-grade yield grade system.
AB  - Beef carcasses (n = 5,542) were evaluated by three USDA on-line graders and
      compared with the computed expert USDA quality (QG) and yield grades (YG) during
      8-h shifts at a major beef-processing facility for a 2-wk period to evaluate the
      accuracy of applying USDA QG and YG within the traditional five-grade and the
      proposed seven-grade (segregating YG 2 and 3 into YG 2A, 2B, 3A, and 3B) YG
      systems. Quality grade distribution of the carcasses was 1.1% Prime, 50.0%
      Choice, 43.8% Select, and 5.1% No-Roll. Accuracy of applying QG was not affected
      (P>.05) by changing from the five-grade (91.5%) to either the seven-grade system,
      when determining only QG (94.3%), or the seven-grade system, when determining QG
      and YG (95.0%). Calculated expert YG successfully segregated carcasses into their
      respective YG, but on-line graders could not differentiate between YG 4 and 5 in
      the seven-grade systems. The application of YG in the five-grade system was more
      accurate (P<.05) than either of the seven-grade systems. A trend existed for on
      line graders to undergrade carcasses as the numerical YG increased. Total
      accuracy of applying YG decreased by 19.4 to 21.8% when switching from the five
      grade to the seven-grade system. The segmentation of USDA YG 2 and 3 into YG 2A,
      2B, 3A, and 3B resulted in a decrease in the ability of on-line graders to
      accurately apply the YG.

PMID- 10064035
TI  - Relationship between development of intramuscular connective tissue and toughness
      of pork during growth of pigs.
AB  - We investigated changes in structures and properties of the endomysium and
      perimysium during development of semitendinosus muscle in relation to the
      increase in toughness of pork using samples from neonates to 55-mo-old pigs. The
      shear force value of pork increased linearly until 6 mo of age, and the rate of
      increase slowed down thereafter. The secondary perimysium thickened owing to an
      increase in the number and thickness of perimysial sheets consisting of collagen
      fibers, which became thicker and wavy with the growth of the pigs. This increase
      in thickness of the secondary perimysium was correlated significantly with the
      increase in the shear force value (r = .98). The endomysial sheaths became
      thicker and denser in the muscle of 6-mo-old pigs. Maturation of the endomysium
      was accompanied by hypertrophy of muscle fibers. The amount of heat-soluble
      collagen decreased almost linearly, indicating that nonreducible cross-links
      between collagen molecules were formed throughout chronological aging. We
      conclude that thickening of the perimysium is closely related to an increase in
      the toughness of pork during growth of pigs.

PMID- 10064036
TI  - Utilization of bioelectrical impedance to predict carcass composition of Holstein
      steers at 3, 6, 9, and 12 months of age.
AB  - The objective of this experiment was to study the usefulness of bioelectrical
      impedance analysis (BIA) in determining soft tissue composition (STC) and carcass
      fat-free mass (CFFM) of Holstein steers at different ages. Growth data and
      prediction of STC and CFFM were determined for four groups of Holstein steers: 12
      of 3 mo, 12 of 6 mo, 15 of 9 mo, and 16 of 12 mo of age. Average weight for
      animals at 3, 6, 9, and 12 mo were 96.6, 204.7, 354.1, and 465.9 kg,
      respectively. Average fat content of carcass soft tissue at 3, 6, 9, and 12 mo
      were 2.6, 9.8, 18.2, and 24.6%, respectively. Average protein content of the
      carcass soft tissue was 20.7% at 3 mo, 20% at 6 mo, 18.30% at 9 mo, and 16.9% at
      12 mo of age. Feed and water were withheld for 20 h before the BIA was applied.
      Steers were sedated and forced to recumbency in a lateral position on their right
      sides over a nonconductive surface. Two electrodes were placed on each limb of
      the right side (metatarsal and metacarpal regions on back and front foot,
      respectively). Resistance (Rs) and reactance (Xc) were obtained by attaching four
      terminals to the electrodes. Impedance and other predictors such as Vol1 (L/Rs),
      Vol2 (L2/(RS2+Xc2).5, Vol3 (geometrical animal volume), L (2 x height + body
      length), and L2 were calculated from Rs and Xc, and body measurements and were
      used to generate prediction equations for CFFM and carcass soft tissue
      composition. Carcass fat-free mass was predicted accurately for all age groups
      and the pooled data (r2 = .99 at 3 mo, .99 at 6 mo, .97 at 9 mo, .77 at 12 mo,
      and .98 for the pooled data). Correlation coefficients between impedance readings
      and CFFM and carcass composition were calculated. Carcass CFFM and kilograms of
      H2O for the pooled data (across age groups) were both correlated highly to Vol1
      (.97), Vol2 (.95), L (.97), and L2 (.97).

PMID- 10064037
TI  - Manipulation of the type of fat consumed by growing pigs affects plasma and
      mononuclear cell fatty acid compositions and lymphocyte and phagocyte functions.
AB  - To investigate the immunological effect of feeding pigs different dietary lipids,
      3-wk-old, weaned pigs were fed for 40 d on one of five diets, which differed only
      in the type of oil present (the oil contributed 5% by weight of the diet and the
      total fat content of the diets was 8% by weight). The oils used were soybean
      (control diet), high-oleic sunflower oil (HOSO), sunflower oil (SO), canola oil
      (CO), and fish oil (FO; rich in long-chain [n-3] polyunsaturared fatty acids).
      There were no significant differences in initial or final animal weights, weight
      gains, or health scores among the groups. There were no significant differences
      in the concentration of anti-Escherichia coli vaccine antibodies in the gut
      lumens of pigs fed the different diets. The fatty acid composition of the diet
      markedly affected the fatty acid composition of the plasma and of mononuclear
      cells (a mixture of lymphocytes, monocytes, and macrophages) prepared from the
      blood, lymph nodes, or thymus. The FO feeding resulted in a significant increase
      in the number of circulating granulocytes. The FO feeding significantly decreased
      the proportion of phagocytes engaged in uptake of E. coli and decreased the
      activity of those phagocytes that were active. The proliferation of lymphocytes
      in cultures of whole blood from pigs fed the HOSO, SO, or FO diets was less than
      in those from pigs fed the CO diet. Proliferation of lymph node lymphocytes from
      SO- or FO-fed pigs was less than that from control, CO-, or HOSO-fed pigs. The
      natural killer cell activity of blood lymphocytes from pigs fed the FO diet was
      significantly reduced compared with those from pigs fed the CO diet. The
      concentration of PGE2 in the medium of cultured blood, lymph node, or thymic
      mononuclear cells was lower if the cells came from pigs fed the FO diet. Thus,
      the type of oil included in the diet of growing pigs affects the numbers and
      functional activities of immune cells in different body compartments.

PMID- 10064038
TI  - Apparent ileal and total-tract nutrient digestion by pigs as affected by dietary
      nondigestible oligosaccharides.
AB  - The effects of two types of nondigestible oligosaccharides (NDO),
      fructooligosaccharides (FOS), and transgalactooligosaccharides (TOS) were studied
      on growing and weanling pigs' nutrient digestion. Dietary NDO were included at
      the expense of purified cellulose. Twenty-five 57-d-old growing pigs, averaging
      15.9+/-.6 kg on d 0 of the experiment, were fed a corn-based control diet or the
      control with 6.8 or 13.5 g of FOS/kg or 4.0 or 8.0 g of TOS/kg (five pigs per
      diet). Feces were collected on d 28 to 32, and small-intestinal digesta were
      collected (slaughter technique) on d 42 to 47 of the experiment. Feeds, feces,
      and digesta were analyzed for DM, inorganic matter, CP, ether extract, and crude
      fiber. Dietary NDO did not significantly affect apparent fecal and small
      intestinal digestion of nutrients in growing pigs. After being fed a NDO-free
      diet through d 10 after weaning, 38-d-old weanling pigs (n = 20), averaging
      10.4+/-.8 kg on d 0 of the experiment, were fed a control diet (based on
      cornstarch, casein, and oat husk meal) or the control with 10 or 40 g of FOS or
      TOS/kg (four pigs per diet). Feces and urine were collected on d 13 to 17, and
      ileal digesta were collected via a postvalve T-cecum cannula on d 33 to 37 of the
      experiment. Feeds, feces, and digesta were analyzed for DM, inorganic matter, CP,
      ether extract, starch, NDF, ADF, ADL, Ca, P, Mg, Fe, Cu, and Zn. Nonstarch
      neutral-detergent soluble carbohydrates (NNSC) completed the mass balance for the
      carbohydrates. Urine was analyzed for N and minerals. The apparent fecal
      digestion of NNSC increased in the NDO-supplemented diets. The TOS-fed pigs
      tended (P<.10) to have a higher apparent fecal digestion of CP than the FOS-fed
      and control pigs but excreted more N via the urine (P<.01). Nitrogen and mineral
      balances were not affected. The FOS was nearly completely degraded prececally.
      Mean fiber digestion was lower at the fecal compared with the ileal level, as was
      the extent of NDO effects. This indicates that fiber digestion requires more than
      2 wk to adapt to dietary NDO. Apparent ileal digestion of hemicellulose increased
      for the NDO-supplemented diets (P<.05), but that of NNSC decreased (P<.001).
      Thus, under the well-controlled conditions of this experiment, dietary NDO hardly
      affected nutrient digestion in well-kept growing and weanling pigs. However,
      digestion of dietary nonstarch carbohydrates may be affected.

PMID- 10064039
TI  - An estimation of the requirement for folic acid in gestating sows: the metabolic
      utilization of folates as a criterion of measurement.
AB  - Sows at their second parity were randomly distributed in five groups of seven
      animals each to determine the dietary concentration of folic acid that optimizes
      the metabolic utilization of the vitamin during gestation. The groups differed by
      dietary supplement of folic acid: 0, 5, 10, 15, or 20 ppm. Sows were fed 2.5 kg
      of diet each day. The response of serum folates and folate binding capacity to
      treatments and the excretion of urinary folates after an i.v. injection of folic
      acid were measured. The total daily excretion of urinary folates was corrected
      according to the response to one i.v. injection of saline on the day preceding
      the i.v. injection of folic acid. The decrease of total serum folates throughout
      gestation was less pronounced in the groups fed 15 and 20 ppm of dietary folic
      acid (supplement x period interaction, P<.06) than it was in the other three
      treatments. The proportion of i.v. folic acid not recovered in sow urine
      (injected - excreted) decreased as the amount of dietary folic acid increased to
      reach a minimum, which differed according to the period (supplement x period
      interaction, P<.02); it was 15 ppm during wk 1 of gestation and 10 ppm for the
      other periods studied. The unrecovered folates increased over a dietary
      concentration of 15 ppm. These minimum values correspond to the most appropriate
      feed concentration that covered the whole body utilization (tissue and cell
      metabolism, catabolism, and storage) of folates by the sows and could be
      interpreted as a reliable index of the requirement.

PMID- 10064040
TI  - The effect of cyclopiazonic acid on the development of pale, soft, and exudative
      pork from pigs of defined malignant hyperthermia genotype.
AB  - Malignant hyperthermia (MH) and the mycotoxin cyclopiazonic acid (CPA) are each
      associated with abnormal calcium homeostasis in skeletal muscle, a key underlying
      factor in the development of pale, soft, and exudative (PSE) pork. To determine
      whether the natural presence of CPA in livestock feed ingredients contributes to
      the varying incidence of PSE in the pork industry, various levels of CPA (.1 to
      50 mg/kg of diet) were included in the diets of market weight hogs (n = 52) of
      defined malignant hyperthermia genotype (NN = normal, Nn = a MH carrier, and nn =
      MH-positive). Animals with two copies of the MH mutation (nn) displayed improved
      live animal performance compared with NN and Nn animals (increased feed intake,
      average daily gain, and feed efficiency) but yielded lower quality loin chops as
      indicated by lower 45-min pH (P<.01), higher Commission Internationale de
      l'Eclairage (CIE) L* color coordinate values (P<.05), and higher drip losses
      (P<.01). The effects of CPA varied. In the first feeding trial, conducted under
      normal outside temperatures (2 degrees C), CPA had no effect (P> .2) on either
      live animal performance or meat quality. During the second trial, conducted under
      extreme outside temperatures (-18 degrees C), CPA-dependent reductions (P<.05) in
      feed intake, average daily gain, and 45-min pH in nn hogs support the possibility
      of interactions between malignant hyperthermia and dietary CPA on skeletal muscle
      calcium homeostasis and the development of PSE pork. These results suggest that
      this interaction may require stressful environmental conditions or the ingestion
      of CPA doses much higher than occur under natural conditions.

PMID- 10064041
TI  - Analysis and pharmacokinetics of cyclopiazonic acid in market weight pigs.
AB  - The pharmacokinetic behavior of cyclopiazonic acid (CPA) was determined in market
      weight pigs using a competitive indirect ELISA developed for the determination of
      the mycotoxin in various biological matrices. Sample preparation for corn and
      skeletal muscle was achieved with a single extraction and recoveries of 53+/-6%
      over the effective range of the standard curve. The detection limit of CPA was 1
      ppb in plasma, which required no extraction, and 20 ppb in corn and skeletal
      muscle with average intra- and interassay CV of 11 and 23%, respectively. Levels
      of CPA contamination in corn grown and stored in Michigan were unremarkable
      compared with published toxicity thresholds; the highest level of CPA found in
      any sample was 47 ppb. In pigs given a 20-mg i.v. bolus, CPA distributed rapidly
      among three compartments, with an overall volume of distribution (49 L) nearly
      equivalent to total body water. Cyclopiazonic acid was eliminated with a half
      life of 24 h. Estimates of these pharmacokinetic parameters were supported by the
      achievement of steady-state plasma CPA levels within 6 d in pigs consuming a diet
      containing 10 ppm CPA, and by measured concentrations of CPA in plasma (410+/-44
      ng/mL) and skeletal muscle (469+/-86 ng/ g). From these and other data, we
      concluded that the threat of CPA toxicity to livestock from consumption of cereal
      grains or to humans from consumption of animal products is minimal.

PMID- 10064042
TI  - Processing, mixing, and particle size reduction of forages for dairy cattle.
AB  - Adequate forage amounts in both physical and chemical forms are necessary for
      proper ruminal function in dairy cows. Under conditions in which total amounts of
      forage or particle size of the forage are reduced, cows spend less time
      ruminating and have a decreased amount of buoyant digesta in the rumen. These
      factors reduce saliva production and allow ruminal pH to fall, depressing
      activity of cellulolytic bacteria and causing a prolonged period of low ruminal
      pH. Insufficient particle size of the diet decreases the ruminal acetate-to
      propionate ratio and reduces ruminal pH. The mean particle size of the diet, the
      variation in particle size, and the amount of chemical fiber (i.e., NDF or ADF)
      are all nutritionally important for dairy cows. Defining amounts and physical
      characteristics of fiber is important in balancing dairy cattle diets. Because
      particle size plays such an important role in digestion and animal performance,
      it must be an important consideration from harvest through feeding. Forages
      should not be reduced in particle size beyond what is necessary to achieve
      minimal storage losses and what can be accommodated by existing equipment. Forage
      and total mixed ration (TMR) particle sizes are potentially reduced in size by
      all phases of harvesting, storing, taking out of storage, mixing, and delivery of
      feed to the dairy cow. Mixing feed causes a reduction in size of all feed
      particles and is directly related to TMR mixing time; field studies show that the
      longest particles (>27 mm) may be reduced in size by 50%. Forage and TMR particle
      size as fed to the cows should be periodically monitored to maintain adequate
      nutrition for the dairy cow.

PMID- 10064043
TI  - Mechanical maceration of alfalfa.
AB  - Maceration is an intensive forage-conditioning process that can increase field
      drying rates by as much as 300%. Because maceration shreds the forage and reduces
      its rigidity, improvements in bulk density, silage compaction, and ensiling
      characteristics have been observed. Macerating forage also increases the surface
      area available for microbial attachment in the rumen, thereby increasing forage
      digestibility and animal performance. Feeding trials with sheep have shown
      increases in DMI of 5 to 31% and increases in DM digestibility of from 14 to 16
      percentage units. Lactation studies have demonstrated increases in milk
      production and BW gain for lactating Holstein cows; however, there is a
      consistent decrease in milk fat percentage when dairy cattle are fed macerated
      forage. In vitro studies have shown that maceration decreases lag time associated
      with NDF digestion and increases rate of NDF digestion. In situ digestibility
      studies have shown that maceration increases the size of the instantly soluble DM
      pool and decreases lag time associated with NDF digestion, but it may not
      consistently alter the rate or extent of DM and NDF digestion.

PMID- 10064044
TI  - A technique for assessing the effects of olfaction on feed preference in
      lactating Holstein cows.
AB  - Our objective was to develop a method for assessing the effects of olfaction on
      feed preference. Two multiparous lactating Holstein cows were offered a totally
      mixed ration consisting of corn silage, alfalfa haylage, and a ground corn and
      soybean meal-based concentrate mixture (25:25:50 on a DM basis) for their ad
      libitum consumption in four consecutive 2.5-h periods daily for 5 d. An apparatus
      was developed that allowed odorants to be distributed at a set rate over two
      feeding containers with limited possibility of odor carryover. Four odorants and
      a control (no odorant) were compared against each other. All possible comparisons
      were conducted on the left and right feeding sides to avoid potential lateral
      preference effects. Rank values of 0 or .5 were assigned to each odorant based on
      the percentage of total feed consumed in a period. A test of overall equality
      based on the sums of squares of ranks was used to determine whether odors
      affected preference. The limited results indicated that inhalation of odorants
      did not affect preference. Rank values were doubled for several odorants when
      compared with others, which suggested that the sample size limited experimental
      sensitivity. To attain reasonable power, we estimated that at least six cows were
      needed per study. Large effects of odorants on feed preference would have been
      required to reach statistical significance in this trial; however, the method
      provides a practical technique for testing the effects of olfaction on feed
      preference in cattle when the suggested number of cows is used.

PMID- 10064045
TI  - Ruminally undegraded intake protein in sheep fed low-quality forage: effect on
      weight, growth, cell proliferation, and morphology of visceral organs.
AB  - To determine the influence of increasing levels of supplemental ruminally
      undegraded intake protein (UIP) on visceral organ weights, growth, cell
      proliferation, and morphology, 20 mature ewes of mixed breeding were fed a 6.55%
      CP grass hay:straw mixture (40:60) and assigned to one of four supplemental
      treatments. Supplements were control (no supplement) and low, medium, and high
      levels of UIP. After 42 to 46 d on treatment, ewes were infused i.v. with 5-bromo
      2-deoxy-uridine (BrdU, a thymidine analog used to provide an index of the rate of
      intestinal cell proliferation) and slaughtered 1 h later. Visceral organs were
      weighed, and subsamples were obtained to evaluate visceral DNA, RNA, and protein
      contents (frozen samples) as well as intestinal morphology (fixed samples). Final
      BW; eviscerated BW (EBW); total visceral weight; and liver fresh, dry, and dry
      fat-free weights were increased (P<.10) in protein-supplemented ewes compared
      with controls, but were not influenced by increasing levels of UIP. Tissue
      weights of duodenum, jejunum, ileum, cecum, and colon were not greatly influenced
      by treatment. There were no differences among treatments in intestinal DNA and
      protein concentrations and the ratios RNA:DNA and protein:DNA. Jejunal RNA
      concentration and content was increased (P<.10) in low compared with medium and
      high treatments. Jejunal RNA content also was decreased (P<.10) in high compared
      with the medium UIP treatment. Liver RNA and protein contents were increased
      (P<.10) with protein supplementation. In contrast, contents of RNA, DNA, and
      protein in duodenum, ileum, cecum, and colon were not influenced by treatment. In
      addition, neither the rate of intestinal proliferation (BrdU labeling) nor
      intestinal morphology (crypt depth, villus length, or villus width) were affected
      by treatment. These data indicate that the influence of protein supplementation
      on visceral growth involves primarily the liver and not the intestines. These
      data also indicate that visceral growth, except in jejunum, are not altered by
      differing levels of UIP supplementation.

PMID- 10064046
TI  - Fermentation substrate and dilution rate interact to affect microbial growth and
      efficiency.
AB  - The effect of dilution rate (D) on carbohydrate, fibrous and nonfibrous, and
      protein fermentation by ruminal microorganisms was studied using a single
      effluent continuous-culture system. The diets of fibrous carbohydrate, nonfibrous
      carbohydrate, or protein were formulated with soybean hulls (FC), ground corn
      (NFC), or isolated soy protein (PR) as the primary ingredient, respectively. Six
      dilution rates (.025, .050, .075, .10, .15, and .20/h of fermenter volume) were
      used. Digestibilities of DM, OM, and CP for the three diets and of NDF and ADF
      for the FC diet decreased (P<.001) as D increased, although the response of the
      digestibility to D varied with diet. Increasing D resulted in an increase in pH
      (P<.001) and a decrease (P<.001) in ammonia concentration. Daily volatile fatty
      acid production increased (quadratic; P<.01) for the FC and NFC diets, but
      decreased (quadratic; P<.001) for the PR diet. Increasing D quadratically
      increased (P<.001) the molar percentage of acetate and propionate, but
      quadratically decreased (P<.001) butyrate and valerate for the FC and NFC diets.
      For the PR diet, the molar percentage of propionate and valerate increased
      (quadratic; P<.01), whereas acetate and butyrate decreased (linear; P<.001) in
      response to increasing D. Molar percentage of isobutyrate and isovalerate
      decreased (P<.01) with increasing D for all three diets. As D increased, daily
      microbial N production showed quadratic responses with maximum values achieved at
      .126, .143, and .187/h D for the FC, NFC, and PR diet, respectively. There was a
      positive correlation between microbial growth efficiency (MOEFF) and D. A
      quadratic model fit the data of MOEFF as affected by D, and maximum MOEFF of
      37.3, 59.6, and 71.4 g of bacterial N/kg OM truly fermented were calculated to be
      achieved at .177, .314, and .207/h D for the FC, NFC, and PR diet, respectively.
      Dilution rate significantly influenced the ruminal microbial fermentation of
      fibrous and nonfibrous carbohydrates and proteins, and was positively related to
      microbial yield and growth efficiency. In addition, microbial nitrogen
      composition, and therefore efficiency, was affected by substrate fermented.

PMID- 10064047
TI  - Nitrogen retention by lambs fed oscillating dietary protein concentrations.
AB  - Nitrogen excreted by beef cattle can be retained in manure or lost by
      volatilization to the atmosphere or by runoff and percolation into surface or
      ground water. Increasing the retention of dietary N should decrease environmental
      losses. To this end, the effects of oscillating concentrations of dietary CP on
      nutrient retention were determined using lambs fed a 90% concentrate diet. Ten
      St. Croix lambs (average BW = 27 kg) were used in two 5x5 Latin square
      experiments. Dietary treatments were as follows: 1) 10% CP, 2) 12.5% CP, 3) 15%
      CP, 4) 10% and 15% CP diets oscillated at 24-h intervals, and 5) 10% and 15% CP
      diets oscillated at 48-h intervals. Supplemental N was provided by cottonseed
      meal in Trial 1 and by a 50:50 (N basis) blend of cottonseed meal and urea in
      Trial 2. Each period of the Latin square lasted 35 d, with excreta collection the
      final 8 d. Nitrogen retention increased linearly (P<.01) with increasing N intake
      in both trials (.77, 1.33, and 1.89 g/d for 10, 12.5, and 15% CP, respectively,
      in Trial 1; .94, 1.78, and 2.19 g/d for 10, 12.5, and 15% CP, respectively, in
      Trial 2). Compared with continuously feeding the 12.5% CP diet, oscillating the
      10 and 15% CP diets on a 24-h basis did not affect N retention (P>.10) in either
      trial (1.62 and 1.56 g/d for Trials 1 and 2, respectively). Oscillating dietary
      CP at 48-h intervals did not affect N retention in Trial 2 (1.82 g/d) but
      increased (P<.05) N retention by 38% in Trial 1 (1.87 g/d). Phosphorus, K, and Na
      retention and excretion were not affected by dietary treatments in Trial 1. In
      Trial 2, P retention increased (linear, P<.05) with increasing dietary CP and was
      greater (P<.05) in lambs on the 48-h oscillation treatment than in lambs fed the
      12.5% CP diet. These results suggest that oscillating the dietary CP
      concentrations might potentially increase the utilization of N by ruminants fed
      high-concentrate diets.

PMID- 10064048
TI  - Effects of pre- or postpartum selenium supplementation on selenium status in beef
      cows and their calves.
AB  - The effect of Se supplementation before or after calving on Se status in
      deficient cows and their calves was studied using 72 beef cows in two
      experiments. In Exp. 1, cows calving in February or March 1997 were supplemented
      orally for 15 d in late pregnancy with 13.0, 32.5, or 45.5 mg of Se/d as sodium
      selenite. Glutathione peroxidase (GSH-Px) activities were measured in red blood
      cells (RBC) or plasma of cows and calves at d 15 and between d 17 and 88 after
      calving. In Exp. 2, cows calving in January 1997 were supplemented orally with
      .0, 13.0, or 32.5 mg of Se/d for 15 d postpartum, and calves were injected with
      1.38 mg of Se when 2 d old and at an average age of 49 d. The GSH-Px activities
      were measured in 30-d-old calves and in cows and calves between d 77 and 115
      after calving. In both experiments, Se supplementation resulted in adequate Se
      status for the dams. The increase in RBC GSH-Px activity was faster with 45.5 mg
      of Se/d, and GSH-Px activities remained high for up to 98 d after the end of
      supplementation. The improvement in Se status in calves as a result of maternal
      supplementation was greater in Exp. 1 than in Exp. 2, suggesting that the
      placental transfer of Se is more efficient than milk transfer. Prepartum oral Se
      supplementation of deficient beef cows with 13.0 mg of Se/d for 15 d allowed
      adequate Se status of dams and calves, and 45.5 mg of Se/d resulted in a faster
      improvement of Se status. Parenteral administration of 1.38 mg of Se to newborn
      calves did not sustain normal Se status in calves issued from deficient cows.

PMID- 10064049
TI  - The effects of low-copper diets with or without supplemental molybdenum on
      specific immune responses of stressed cattle.
AB  - Angus bull calves (n = 42; 7 mo of age; 254 kg initial BW) were used to
      investigate the effects of dietary Cu and Mo on immune function of stressed
      cattle. Randomly selected calves (n = 22) were injected with 90 mg of Cu as Cu
      glycinate 28 d before weaning and castrated at weaning. These calves received 7.5
      and 5 mg of supplemental Cu/kg of DM during a 41-d receiving phase and a 196-d
      growing phase, respectively. The remainder of the steers received no supplemental
      Cu during the experiment. Copper-supplemented steers had adequate Cu status at
      weaning, whereas unsupplemented calves were marginally Cu-deficient. Cell
      mediated response to intradermal injection of phytohemagglutinin was not affected
      by dietary treatment during the receiving phase. During the growing phase, half
      of the steers in each Cu treatment were given 5 mg of supplemental Mo/kg of DM.
      Copper supplementation increased (P<.05) humoral response to ovalbumin injected
      on d 133 of the growing phase. On d 168 of the growing phase, calves receiving
      only supplemental Mo were severely Cu-deficient based on plasma and liver Cu
      concentrations. The other treatment groups had adequate Cu status. Before feeding
      on d 168 of the growing phase, half of the steers were loaded onto trailers and
      transported 2.5 h, and they remained on the trailers an additional 9.5 h. Humoral
      response to porcine erythrocytes (PRBC) and delayed-type hypersensitivity (DTH)
      to dinitrochlorobenzene was tested at the end of the stress period. There was a
      Cu x stress interaction for humoral response to PRBC, with Cu decreasing antibody
      titers in unstressed calves and increasing titers in stressed steers. Stressed
      steers had lower (P = .03) ADG during the 28 d following stress. The results of
      this study indicate that Cu deficiency and 5 mg of supplemental Mo/kg of DM do
      not dramatically alter the specific immunity of stressed cattle.

PMID- 10064050
TI  - Relationship between ruminal starch degradation and the physical characteristics
      of corn grain.
AB  - The objectives of this study were to determine the range of variation in the rate
      and extent of in situ ruminal starch degradation of 14 corns differing in
      vitreousness and to predict ruminal starch degradability by physical
      characteristics of corn grains. This study was conducted with eight dent and six
      flint corns. Ruminal starch degradability was determined by an in situ technique
      on 3-mm ground grains. Physical characteristics of corn grain were measured:
      hardness by grinding energy and particle size distribution, apparent and true
      densities, and specific surface area. Ruminal DM and starch degradabilities
      averaged 50 and 55.1% and varied from 39.7 to 71.5% and from 40.6 to 77.6%,
      respectively. Ruminal starch degradability averaged 61.9 and 46.2% in dent and
      flint types, respectively. The proportion of coarse particles (61.9 vs. 69.6% for
      dent and flint, respectively), the apparent density (1.29 vs. 1.36 g/cm3 for dent
      and flint, respectively), and the specific surface area (.13 vs. .07 m2/g for
      dent and flint, respectively) varied with the vitreousness. Ruminal starch
      degradability could be predicted accurately by vitreousness (r2 = .89) or by the
      combination of apparent density and 1,000-grain weight (R2 = .91), a measurement
      faster than the vitreousness determination.

PMID- 10064051
TI  - Copper status of ewes fed increasing amounts of copper from copper sulfate or
      copper proteinate.
AB  - The Cu status of mature, crossbred ewes fed two sources (CuSO4 vs. Cu proteinate)
      and three levels (10, 20, or 30 mg/kg) of dietary Cu was determined in a 73-d
      feeding trial. Ewes (n = 30) were fed a basal diet containing rice meal feed,
      cottonseed hulls, cottonseed meal, meat and bone meal, cracked corn, and vitamin
      mineral supplements at 2.5% of BW to meet NRC requirements for protein, energy,
      macrominerals, and microminerals, excluding Cu. The basal diet contained 5 mg/kg
      Cu, 113 mg/kg Fe, .1 mg/kg Mo, and .17% S. Copper sulfate or Cu proteinate was
      added to the basal diet to supply 10, 20, or 30 mg/kg of dietary copper in a 2x3
      factorial arrangement of treatments. Ewes were housed in 3.7- x 9.1-m pens in an
      open-sided barn. Blood samples were collected on d 28 and 73. Ewes were
      slaughtered on d 74, and liver and other tissues were collected to determine Cu
      concentrations. An interaction (P = .08) occurred between source and level for
      liver Cu. The interaction existed due to an increase in liver Cu concentrations
      when ewes were fed increasing dietary Cu from CuSO4 but not when fed Cu
      proteinate diets. There was no source x level interaction (P>.10) for the blood
      constituents measured. On d 73, plasma ceruloplasmin activity was greater (P<.05)
      in ewes fed Cu proteinate than in those fed CuSO4 (33.1 vs. 26.8 microM x min(-1)
      x L(-1)). Increasing the concentration of dietary Cu did not affect (P>.10)
      plasma ceruloplasmin. Packed cell volume (PCV), red blood cell count (RBC), white
      blood cell count, whole blood hemoglobin (wHb), plasma hemoglobin, and plasma Cu
      were similar between sources of Cu. Ewes fed 20 mg/kg Cu had lower (P<.05) PCV,
      RBC, and wHb than those fed 10 or 30 mg/kg Cu diets. Feeding up to 30 mg/kg Cu
      from these sources did not cause an observable Cu toxicity during the 73-d
      period.

PMID- 10064052
TI  - Identification of an IL-8 homolog in lamprey (Lampetra fluviatilis): early
      evolutionary divergence of chemokines.
AB  - Subtractive hybridization was used to study river lamprey (Lampetra fluviatilis)
      leukocyte-specific cDNA. A clone representing the most abundant component (12%)
      of the leukocyte library subtracted with liver cDNA was isolated and
      characterized. The cDNA encodes a presumably secreted polypeptide of 101
      residues. The 3' untranslated region of the cDNA contains motifs characteristic
      of the transiently expressing genes. Comparison of the deduced amino acid
      sequence with known protein sequences revealed its homology to the members of the
      chemokine superfamily. Designated as LFCA-1, the lamprey protein contains four
      conserved cysteines, of which the first two are separated by a residue, and a
      number of other CXC family characteristic residues. LFCA-1 has the highest
      similarity to the chicken EMF-1 (40%) and to the mammalian IL-8 (32-33%).
      However, it lacks the ELR motif essential for the function of the mammalian IL-8
      related chemokines. Based on the phylogenetic analysis of the LFCA-1 relationship
      to the higher vertebrate chemokines, it is concluded that the evolutionary origin
      of the chemokine superfamily is ancient, and that the divergence of the CXC and
      CC families most likely occurred at the time or before the first vertebrates
      emerged.

PMID- 10064053
TI  - Regulation of cell surface expression of Fas (CD95) ligand and susceptibility to
      Fas (CD95)-mediated apoptosis in activation-induced T cell death involves
      calcineurin and protein kinase C, respectively.
AB  - We show that an influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP
      12-7) enters the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated
      pathway upon T cell receptor (TCR) stimulation. These cells express Fas and FasL
      mRNA, cell surface Fas and intracellular FasL, but do not enter apoptosis upon
      Fas ligation prior to TCR stimulation. TCR stimulation additionally results in
      protein synthesis-dependent cell surface expression of the preformed FasL.
      Addition of phorbol dibutyrate (PBu2) alone was sufficient to induce
      susceptibility to Fas ligation induced apoptosis, while addition of both PBu2 and
      calcium ionophore A23187 were required to induce FasL cell surface expression.
      Addition of cyclosporin A completely inhibited TCR-mediated death and FasL cell
      surface up-regulation, but had no effect on apoptosis induced directly by Fas
      ligation following TCR stimulation. Inhibitors of protein kinase C (PKC) (Go 6976
      and GF 109203X) completely inhibited TCR-induced susceptibility to Fas ligation,
      but only partially inhibited TCR-induced cell surface expression of FasL. PKC
      isoenzymes alpha, beta, delta and zeta were expressed by this cell line and only
      the alpha and betaI isoforms translocated to the membrane fraction upon TCR
      stimulation. Our data suggest that in activation-induced T cell apoptosis PKC is
      involved in pathways that mediate the acquisition of Fas susceptibility, while
      calcineurin is required for cell surface expression of the preformed FasL.

PMID- 10064054
TI  - Inhibition of thymocyte positive selection by natural MHC: peptide ligands.
AB  - The 3A9 transgenic mouse line carries the rearranged TCR genes from a T cell
      hybridoma that recognizes hen egg lysozyme peptide 46-61 in the context of MHC
      class II Ak molecules. As expected, positive selection of immature 3A9 thymocytes
      to become mature CD4+ 8- T cells was efficient on the "selecting" CBA (H-2k)
      genetic background but not on the "non-selecting" C57BL/6 (H-2b) background.
      Surprisingly, positive selection was also inefficient on the CBA x C57BL/6 F1
      background (H-2kb). We present evidence that expression of A(beta)b molecules on
      thymus epithelium (in conjunction with A(alpha)b or A(alpha)k molecules) inhibits
      the positive selection of 3A9 thymocytes mediated by A(alpha)k:A(beta)k
      complexes, in a process evocative of peptide antagonism of mature T cells.

PMID- 10064055
TI  - Spontaneous clustering of Thy-1 antigens on CD4+ CD8+ thymocytes lacking TCR
      engagement by MHC/peptide complexes.
AB  - While much is known concerning CD4+ CD8+ thymocytes positively or negatively
      selected through interaction of their TCR with self peptides bound to self-MHC
      molecules, little is known of the majority of CD4+ CD8+ thymocytes lacking this
      interaction. We developed a monoclonal antibody (mAb) 1D11, the ligand of which
      (1D11-L) is expressed on 60-70% of CD4+ CD8+ thymocytes but not on other subsets
      of thymocytes and peripheral T cells. 1D11-L expression on CD4+ CD8+ thymocytes
      reversely correlates with their TCR engagement, in vitro and in vivo. In
      addition, 1D11-L+ CD4+ CD8+ thymocytes were more susceptible than 1D11-L- CD4+
      CD8- thymocytes to apoptosis. We also found that T lineage cells other than CD4+
      CD8+ thymocytes and a Thy-1-expressing fibroblast cell line became positive for
      1D11-L by cross-linking their Thy-1 antigens with anti-Thy-1 mAb but not with
      their Fab fragment, suggesting that 1D11 recognizes multimerized Thy-1 antigens.
      Confocal laser scanning microscopy revealed that Thy-1 antigens as well as 1D11-L
      are clustered on some CD4+ CD8+ thymocytes but not on the other subsets of
      thymocytes. Taken together, we suggest that clustering of Thy-1 antigens
      spontaneously and specifically occurs on CD4+ CD8+ thymocytes lacking TCR
      engagement by MHC/peptide complexes.

PMID- 10064056
TI  - Lipid A directly inhibits IL-4 production by murine Th2 cells but does not
      inhibit IFN-gamma production by Th1 cells.
AB  - Lipopolysaccharide (LPS) is known to be an immunopotentiator but its effect on
      cytokine production by Th1 and Th2 cells is unknown. We found that high amounts
      of LPS, its lipid A moiety, and a lipid A analog all induced a decrease in IL-4
      production and an increase in IFN-gamma production when given to keyhole limpet
      hemocyanin (KLH)-restimulated lymph node cells prepared from KLH-primed mice.
      Lipid A was similarly found to inhibit IL-4 production by purified CD4+ T cells
      and Th2 clones activated with immobilized anti-CD3epsilon and anti-CD28
      antibodies, suggesting that the inhibition is not indirectly mediated through
      effects on antigen-presenting cells. No inhibitory effect of lipid A was observed
      on IFN-gamma production by a Th1 clone. Production of both IL-4 by the Th2 clones
      and IFN-gamma by the Th1 clone were inhibited by the immunosuppressive agent
      cyclosporin A. These findings indicate that lipid A can directly inhibit IL-4
      production by CD4+ T cells without inhibiting the production of IFN-gamma. Lipid
      A may therefore become a useful tool to study the intracellular events that
      differentiate Th1 and Th2 cells.

PMID- 10064057
TI  - Novel chondroitin sulfate-modified ligands for L-selectin on lymph node high
      endothelial venules.
AB  - The migration of lymphocytes into lymph nodes via high endothelial venules (HEV)
      is dependent on the expression of L-selectin on the lymphocyte cell surface. HEV
      express several L-selectin ligands including CD34, GlyCAM-1, MAdCAM-1 and two
      sulfated glycoproteins (Sgp) of 200 kDa and 170 kDa which remain to be
      identified. In this investigation, labeling with sodium [35S]sulfate, which is
      incorporated into and forms part of the functional carbohydrate ligand, has been
      used to isolate and characterize macromolecular L-selectin ligands. High
      endothelial cells (HEC) cultured from rat lymph node HEV were shown to express
      ligands for L-selectin. HEC synthesized two groups of sulfated glycoproteins of
      150 kDa and > 200 kDa, which were present in conditioned medium. These coeluted
      on anion exchange chromatography at 1.0-1.2 M NaCl and supported calcium
      dependent L-selectin-mediated cell adhesion. In common with known L-selectin
      ligands, Sgp 150/> 200 were shown to be O-sialoglycoproteins; however, in
      contrast to other ligands, Sgp 150/> 200 contained chondroitin sulfate
      glycosaminoglycan modifications which were required for L-selectin recognition.
      Chondroitin sulfate-modified ligands for L-selectin were expressed at the HEC
      surface and by HEV in lymph nodes, suggesting that they may participate in
      lymphocyte interactions with HEV in vivo.

PMID- 10064058
TI  - Peptide length-dependent TCR antagonism on class II HLA-restricted responses of
      peripheral blood mononuclear cells and T cell clones.
AB  - T cell clonal recognition of peptide ligands is highly diverse. To investigate
      how peptide mixtures with diverse sequences affect polyclonal responses of
      peripheral blood mononuclear cells (PBMC), we synthesized Xn (n = 9-19) peptides
      that consist of 9 to 19 residues with random sequences. We found that: (1) in
      antagonism assays, Xn peptides inhibit polyclonal responses of PBMC induced by
      purified protein derivative (PPD) and crude mite extracts as well as mixed
      lymphocyte reaction (MLR), in which intermediate-length peptides (n = 13 or 15)
      show the largest inhibitory effects; and (2) a high-affinity HLA-DR4-binding
      peptide is devoid of inhibitory activity against MLR to DR4, indicating that
      these effects are not caused by inhibition of peptide binding to HLA.
      Furthermore, X15 did not abrogate PBMC proliferation induced by phorbol 12
      myristate 13-acetate + ionomycin, or anergize PBMC by preculture. All these
      observations indicate that TCR antagonism does exist at peripheral T cell levels
      in humans, and that Xn peptides, depending on peptide length, are capable of
      antagonizing T cell polyclonal responses. Indeed, even with cloned T cells,
      certain non-agonistic peptides shorter (but not too short) than the wild type in
      their C termini, function as TCR antagonists, findings which corroborate the
      observation that X13-15 antagonizes T cell responses more efficiently than does
      X17-19 or X9-11.

PMID- 10064059
TI  - Anti-Vbeta8 antibodies induce and maintain staphylococcal enterotoxin B-triggered
      Vbeta8+ T cell anergy.
AB  - The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)
      induced T cell anergy is poorly understood. We demonstrated earlier that B cells
      play an important role in the maintenance of SEB-induced T cell anergy in vivo
      and in vitro. Here, we demonstrate that B cells are not essential in SEB-induced
      T cell activation, but are important for the maintenance of T cell memory
      phenotype and anergy in vivo. Studying the activated B cell repertoire, we
      observe that SEB treatment increases serum anti-Vbeta8 antibody titer as detected
      by enzyme-linked immunosorbent assay using soluble Vbeta8 chains as antigens, and
      by staining of a Vbeta8-expressing thymoma. These antibodies disappear gradually
      after immunization with SEB, whereas the capacity of the T cells to respond to
      SEB in vitro is restored. Anti-Vbeta8 monoclonal antibody treatment causes
      Vbeta8+ T cell unresponsiveness to SEB in vitro (anergy), without affecting
      CD4Vbeta8+ T cell frequency. Together, these results suggest a new mechanism to
      explain the maintenance of SEB-induced T cell anergy, which is dependent on B
      cells and on anti-Vbeta8 antibody that specifically interacts with Vbeta8+ T
      cells.

PMID- 10064060
TI  - Immunization through dermal delivery of protein-encoding DNA: a role for
      migratory dendritic cells.
AB  - The early mechanisms by which DNA-dependent immunization occurs remain poorly
      understood. We determined whether intradermal injection of a cytomegalovirus
      (CMV) promoter-driven plasmid encoding hen egg lysozyme (pCMV:HEL) induced
      sensitization against the encoded protein, and whether cutaneous dendritic cells
      (DC) were involved in this sensitization. Both humoral and cellular responses to
      HEL were observed. DC that migrated from skin explant culture 3 days after
      injection of pCMV:HEL DNA contained mRNA encoding HEL. They induced a 3.5-7-fold
      increase in [3H]thymidine incorporation by HEL protein-primed CD4+ T cells
      compared to that induced by DC from mice injected with control plasmid. DC
      emigrating from skin explants recovered from pCMV:HEL injected mice also
      sensitized naive mice after adoptive transfer and induced the generation of CTL.
      Thus following DNA delivery within the dermis, DC can induce primary and
      secondary immune responses.

PMID- 10064061
TI  - Apoptosis of pancreatic beta-cells detected in accelerated diabetes of NOD mice:
      no role of Fas-Fas ligand interaction in autoimmune diabetes.
AB  - Autoreactive T lymphocytes probably cause pancreatic beta-cell death by inducing
      apoptosis. To visualize apoptotic beta-cells in vivo, we accelerated diabetes of
      NOD mice with cyclophosphamide (CY) or adoptive transfer. We also studied whether
      Fas-mediated apoptosis is involved in the development of diabetes by
      administrating anti-Fas ligand (FasL) Ab and by grafting Fas-deficient neonatal
      pancreas from NOD-lpr/lpr mice. Apoptotic cells were clearly shown 8 days after
      CY treatment. Beta-cell apoptosis was also observed after adoptive transfer but
      in a different kinetic pattern. Anti-FasL Ab administration failed to inhibit
      diabetes after CY treatment or adoptive transfer, while it inhibited Con A
      induced hepatitis. Fas-deficient neonatal pancreata were destroyed by lymphocytic
      infiltration in diabetic NOD mice. Our results clearly demonstrate apoptosis of
      beta-cells in accelerated diabetes and indicate that Fas-FasL interaction is not
      involved in diabetes of NOD mice, contrary to the previous reports.

PMID- 10064062
TI  - Inhibition of protein kinase C alpha expression by antisense RNA in transfected
      Jurkat cells.
AB  - Taking the antisense approach to inhibit the expression of specific protein
      kinase C (PKC) isoforms, we investigated the function of PKC alpha in T cell
      activation by transfecting Jurkat cells with an episomal vector (pREP3)
      containing a copy of the corresponding gene in the antisense orientation.
      Transfected Jurkat cells were selected with hygromycin and cloned by limiting
      dilution. Two (as1/as2) stably transfected antisense PKC alpha-pREP3 clones (as
      PKC alpha-pREP3) exhibited consistently reductions (76% and 85%, respectively) of
      PKC alpha levels when analyzed by immunoblotting and immunoprecipitation and also
      of PKC alpha mRNA (75%, as determined by Northern blotting) when compared to
      control clones (C1/C2) containing the pREP3 vector alone. The ability of the as
      PKC alpha-pREP3 construct to specifically reduce PKC alpha levels in both clones
      was demonstrated by Western blots probed with antibodies against the PKC beta
      isozyme (the form structurally more similar to PKC alpha) and other
      representative isoenzymes expressed in Jurkat cells (PKC delta, epsilon, theta,
      and mu). Stimulation of transfected Jurkat clones with phorbol-12-myristate-13
      alone or in the presence of ionomycin resulted in significant reduction of IL-2R
      alpha expression, TNF-alpha production, and the induction of transcriptional
      activity of a pIL-2/Luc construct in both as PKC alpha-reduced clones. The
      magnitude of these decrements paralleled the reductions of PKC alpha expression.
      The loss of the effects in clone as1 after a high number of passages correlated
      with the recovery of normal levels of PKC alpha protein, suggesting a link
      between these processes. Thus, the findings of this study demonstrate the
      essential role that PKC alpha plays in major events of the T lymphocyte
      activation process.

PMID- 10064063
TI  - Defective immunoglobulin class switching in Vav-deficient mice is attributable to
      compromised T cell help.
AB  - Vav, a guanine nucleotide exchange factor for members of the Rho family of small
      GTPases, is activated through engagement of B and T lymphocyte antigen receptors.
      It is important for establishing the signaling threshold of the TCR, as mice
      lacking Vav display defective thymocyte selection. Here, conventional B cells are
      shown to develop normally in Vav-deficient mice but these mice have few B-1 B
      cells. The threshold for inducing B cell proliferation through BCR engagement in
      vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice
      have normal antibody responses to haptenated Ficoll. In contrast, Vav-/- mice
      show defective class switching to IgG and germinal center formation when
      immunized with haptenated protein. Interestingly, this defect is reversed in
      chimeras where normal T cells are present. Antigen-specific proliferation of T
      cells in the T zone was found to be similar in wild-type and Vav-/- mice but the
      induction of IL-4 mRNA and switch transcripts was specifically impaired. These
      results suggest that defective immunoglobulin class switching in Vav-deficient
      mice is attributable to compromised T cell help.

PMID- 10064064
TI  - AML and Ets proteins regulate the I alpha1 germ-line promoter.
AB  - The immunoglobulin heavy chain (IgH) class switch recombination of B lymphocytes
      preferentially targets unrearranged IgH genes that have already been rendered
      transcriptionally active. Transcription of the germ-line IgH genes is controlled
      by intervening (I) regions upstream of their switch regions. The I alpha1
      promoter activates transcription of the human germ-line C alpha1 gene for IgA1
      and mediates the transforming growth factor (TGF)-beta1 responsiveness of this
      locus. Here we show that the I alpha1 promoter contains several binding sites for
      the AML/PEBP2/CBF family of transcription factors and that AML and Ets proteins
      are major regulators of the basal and TGF-beta-inducible promoter activity. Our
      data constitute a starting point for studies to elucidate the molecular mechanism
      by which TGF-beta regulates IgA production.

PMID- 10064065
TI  - Distinct regulation of HLA class II and class I cell surface expression in the
      THP-1 macrophage cell line after bacterial phagocytosis.
AB  - Expression of HLA and CD1b molecules was investigated in the THP-1 macrophage
      cell line within 2 weeks following phagocytosis of mycobacteria or Escherichia
      coli. During the first 2-3 days, cell surface expression of HLA class II and CD1b
      was drastically down-modulated, whereas HLA class I expression was up-modulated.
      In the following days both HLA class II and CD1b expression first returned to
      normal, then increased and finally returned to normal with kinetics similar to
      that observed for the steadily increased HLA class I. The initial down-modulation
      of HLA class II and CD1b cell surface antigens was absolutely dependent on
      phagocytosis of bacteria. Further studies indicated that initial HLA class II
      cell surface down-modulation (1) was not due to reduced transcription or
      biosynthesis of mature HLA class II heterodimers, (2) was only partially, if at
      all, rescued by treatment with IFN-gamma, although both mRNA and corresponding
      intracellular proteins increased up to sixfold with respect to untreated cells,
      and (3) resulted in failure of THP-1 cells to process and present mycobacterial
      antigens to HLA-DR-restricted antigen-specific T cell lines. The existence of a
      transient block of transport of mature HLA class II heterodimers to the cell
      surface in the first days after phagocytosis of bacteria may have negative and
      positive consequences: it decreases APC function early but it may increase it
      later by favoring optimal loading of bacterial antigens in cellular compartments
      at high concentration of antigen-presenting molecules.

PMID- 10064066
TI  - The macrophage scavenger receptor type A directs modified proteins to antigen
      presentation.
AB  - Scavenger receptors constitute a family of cell surface receptors that
      internalize endotoxins, oxidized low-density lipoproteins (oxLDL) and other
      proteins with clustered negative charges for degradation in macrophages. They
      were recently proposed to play a role in antigen presentation but the type of
      scavenger receptor involved in this process has not been known. In this report,
      we have examined the cellular immune responses to modified proteins in mice
      lacking the SR-A scavenger receptor (SRAKO) and their wild-type (ICR) controls.
      While spleen cells of ICR mice immunized with maleylated murine serum albumin
      (Mal-MSA) exhibit strong proliferative responses to the antigen, no such
      responses were found in SRAKO mice. However, addition of SR-A+ antigen-presenting
      cells from ICR mice unmasked proliferative responses to Mal-MSA in spleen
      cultures of immunized SRAKO mice. Similarly, addition of SR-A+ antigen-presenting
      cells was necessary to detect T cell responses in spleen cultures of oxLDL
      immunized SRAKO mice. This indicates that SR-A can mediate uptake of modified
      antigens for presentation to antigen-specific T cells. The fact that cellular
      immunity developed in SRAKO mice implies that other scavenger receptor(s) also
      internalize modified antigens for presentation in vivo. These observations show
      that scavenger receptors participate in immune recognition of oxidized protein
      antigens; this system may be important for recognition of damaged macromolecules
      but could also play a role in autoimmunity.

PMID- 10064067
TI  - Ability of macrophage subsets to transfer resistance to murine leishmaniasis is
      dependent on IL-12 production.
AB  - Leishmania major, which causes cutaneous leishmaniasis in humans, can also infect
      mice, in which can cause either a local cutaneous lesion or a fatal disseminated
      infection. We have previously shown that BALB/c mice injected with antigen-pulsed
      macrophages derived from bone marrow with granulocyte-macrophage colony
      stimulating factor (GMMphi), but not other types of macrophages, were protected
      from an otherwise lethal infection with L. major The protection induced by GMMphi
      was shown to be antigen specific and correlated with the induction of a Th1-like
      response characterized by production of high levels of IFN-gamma, delayed-type
      hypersensitivity reactivity and long-lived resistance to reinfection. In this
      report, we show that the protection induced in this disease model correlates with
      the sustained production of IL-12 synthesis by GMMphi in vitro and in vivo.
      Moreover, GMMphi deficient in the production of IL-12 were unable to induce
      protection in this model. Our data, therefore, suggest that a defect in
      macrophage activation or differentiation may play a significant role in the
      inability of BALB/c mice to respond effectively to L. major, and this mechanism
      may also be important in determining resistance to other intracellular parasites.

PMID- 10064068
TI  - C-X-C and C-C chemokine expression and secretion by the human colonic epithelial
      cell line, HT-29: differential effect of T lymphocyte-derived cytokines.
AB  - Differential chemokine production by colonic epithelial cells is thought to
      contribute to the characteristic increased infiltration of selected population of
      leukocytes cells in inflammatory bowel disease. We have previously demonstrated
      that IL-13 enhances IL-1alpha-induced IL-8 secretion by the colonic epithelial
      cell line HT-29. We have now explored the C-C chemokine expression and modulation
      in this system. The combination of TNF-alpha and IFN-gamma was the minimal
      stimulation required for regulated on activation, normal T cell expressed and
      secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression
      and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA
      expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly
      the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast,
      IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment
      of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C
      chemokine expression is via activation of a wortmannin-sensitive
      phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial
      cell chemokine production can be differentially regulated by T cell-derived
      cytokines and suggest an interplay between epithelial cells and T lymphocytes
      potentially important in the intestinal inflammation.

PMID- 10064069
TI  - Cell surface expression of HLA-E: interaction with human beta2-microglobulin and
      allelic differences.
AB  - The formation of a trimeric complex composed of MHC class I heavy chain, beta2
      microglobulin (beta2m) and peptide ligand is a prerequisite for its efficient
      transport to the cell surface. We have previously demonstrated impaired
      intracellular transport of the human class Ib molecule HLA-E in mouse myeloma X63
      cells cotransfected with the genes for HLA-E and human beta2m (hbeta2m), which is
      most likely attributable to inefficient intracellular peptide loading of the HLA
      E molecule. Here we demonstrate that cell surface expression of HLA-E in mouse
      cells strictly depends on the coexpression of hbeta2m and that soluble empty
      complexes of HLA-E and hbeta2m display a low degree of thermostability. Both
      observations imply that low affinity interaction of HLA-E with beta2m accounts to
      a considerable extent for the observed low degree of peptide uptake in the
      endoplasmic reticulum. Moreover, we show that the only allelic variation present
      in the caucasoid population located at amino acid position 107 (Gly or Arg)
      greatly affects intracellular transport and cell surface expression upon
      transfection of the respective alleles into mouse cells. No obvious difference
      was found with regard to the sequence of the peptide ligand.

PMID- 10064070
TI  - Induction of interferon-gamma production in Th1 CD4+ T cells: evidence for two
      distinct pathways for promoter activation.
AB  - IFN-gamma produced by CD4+ T helper 1 (Th1) cells promotes protection against
      intracellular pathogens. Antigen activation of Th1 cells is an important mode of
      IFN-gamma induction, but here we analyze a second, antigen-nonspecific pathway
      capable of inducing full IFN-gamma transcription. IL-12 or IL-18 alone do not
      induce IFN-gamma mRNA, and only modestly augment antigen-induced IFN-gamma mRNA
      from Th1 cells. However, IL-12 and IL-18 together fully induce IFN-gamma
      transcription independently of TCR-activated signals, by a mechanism that does
      not simply involve Stat4 and NF-kappaB activation, but requires additional
      protein synthesis. Cyclosporin A inhibits TCR-induced IFN-gamma production, but
      not IL-12/IL-18-induced IFN-gamma production, biochemically discriminating
      between these pathways. These results suggest that the two pathways induce IFN
      gamma production through functionally segregated but spatially overlapping cis
      acting elements, similar to other genes under the control of two or more
      promoters.

PMID- 10064071
TI  - Clusters of glycolipid and glycosylphosphatidylinositol-anchored proteins in
      lymphoid cells: accumulation of actin regulated by local tyrosine
      phosphorylation.
AB  - Lateral cross-linking of glycosylphosphatidylinositol (GPI)-anchored proteins and
      glycosphingolipids can trigger a signaling cascade which leads to activation of
      lymphoid cells. A possible explanation how the signal is transduced through the
      plasma membrane has arisen from the concept of raft sphingolipid-cholesterol
      microdomains in cell membranes. Cross-linking of GPI-anchored proteins,
      glycolipids and other raft components leads to the formation of stabilized
      membrane patches in the plasma membrane which enrich members of the Src-tyrosine
      kinase family. We have studied cellular responses to raft patch formation in the
      Jurkat T cell line and in particular changes in the actin cytoskeleton. We found
      that raft patches formed by GPI-anchored CD59 protein and the ganglioside GM1
      accumulate filamentous actin. Most interestingly, we observed a strong
      accumulation of tyrosine-phosphorylated proteins in raft patches, strongly
      supporting the view that they can function as centers of signal transduction.
      Using a Lck kinase-deficient variant of Jurkat cells and a specific Lck and Fyn
      tyrosine kinase inhibitor we found that enrichment of actin in raft patches is
      dependent on phosphotyrosine accumulation in the patches. These observations show
      a link between raft-mediated signaling and the interaction of actin cytoskeleton
      with raft membrane domains.

PMID- 10064072
TI  - Granulocyte-macrophage colony-stimulating factor protects dendritic cells from
      liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a
      Bcl-2-mediated pathway.
AB  - Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for
      depleting cells of the monocyte-macrophage lineage. We have undertaken this study
      to investigate whether dendritic cells are susceptible to this liposome
      encapsulated compound. Dendritic cells were cultured in the presence of L-MDP and
      further processed for apoptosis detection. The highly characteristic DNA cleavage
      into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA
      strand breaks and the typical ultrastructural features of apoptosis were evident
      in dendritic cells exposed to the drug. More importantly, we demonstrated that
      granulocyte-macrophage colony-stimulating factor protects dendritic cells not
      only from apoptosis induced by the exogenous compound but also from spontaneous
      apoptosis. Western blot analysis revealed that this protection was tightly
      correlated with the activation of a Bcl-2-mediated pathway. Regulation of the
      apoptotic threshold of dendritic cells will be advantageous for the generation of
      new insights in immunotherapy.

PMID- 10064073
TI  - Human epidermal Langerhans cells lack functional mannose receptors and a fully
      developed endosomal/lysosomal compartment for loading of HLA class II molecules.
AB  - Langerhans cells (LC) represent the dendritic cell (DC) lineage in the epidermis.
      They capture and process antigens in the skin and subsequently migrate to the
      draining lymph nodes to activate naive T cells. Efficient uptake and processing
      of protein antigens by LC would, therefore, seem a prerequisite. We have now
      compared the capacity of human epidermal LC, blood-derived DC and peripheral
      blood mononuclear cells to endocytose and present (mannosylated) antigens to
      antigen-specific T cells. Moreover, we have determined the expression of mannose
      receptors, and the composition of the intracellular endosomal/lysosomal MHC class
      II-positive compartment. The results indicate that LC have poor endocytic
      capacity and do not exploit mannose receptor-mediated endocytosis pathways.
      Furthermore, the composition of the class II compartment in LC is distinct from
      that in other antigen-presenting cells and is characterized by the presence of
      relatively low levels of lysosomal markers. These results underscore the unique
      properties of LC and indicate that LC are relatively inefficient in antigen
      uptake, processing and presentation. This may serve to avoid hyper-responsiveness
      to harmless protein antigens that are likely to be frequently encountered in the
      skin due to (mechanical) skin damage.

PMID- 10064074
TI  - The resistance against Listeria monocytogenes and the formation of germinal
      centers depend on a functional death domain of the 55 kDa tumor necrosis factor
      receptor.
AB  - The biological functions mediated by the death domain of the 55-kDa tumor
      necrosis factor receptor (TNFRp55) in vivo are still elusive. TNFRp55 mutants
      lacking a functional death domain were expressed in TNFRp55-/- and in TNFRp55+/-
      mice as transgenes under control of the H-2Kb promoter. Analysis of these animals
      revealed that signals originating from the TNFRp55 death domain are indispensable
      for the protection against Listeria monocytogenes, the expression of mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1) in the spleen and the development
      of splenic germinal centers. Furthermore, the transgenic coexpression of the
      TNFRp55 mutants in TNFRp55+/- mice exerts a dominant negative effect on the
      signaling of the endogenous receptor chains in vivo.

PMID- 10064075
TI  - A natural cytotoxic T cell response in a spontaneously regressing human melanoma
      targets a neoantigen resulting from a somatic point mutation.
AB  - We have studied a case of human primary melanoma displaying the classical signs
      of a spontaneous regression in order to characterize potentially efficient anti
      tumor T cell responses. In a previous series of experiments a unique TCR Vbeta16+
      T cell was shown to be highly expanded at the tumor site. The corresponding clone
      was isolated in vitro and found to be a CD8+ cytotoxic T lymphocyte with a strong
      and selective cytolytic activity against the autologous tumor cell line. Here, we
      demonstrate that this predominant Vbeta16+ tumor-infiltrating lymphocyte
      recognizes a peptide encoded by a novel unconventional myosin class I gene. This
      peptide includes a mutation due to a single nucleotide substitution. The
      resulting Glu-->Lys replacement at position 911 of the coding sequence is
      critical to generate the recognized T cell epitope. These experiments demonstrate
      the existence of a natural tumor-specific cytolytic T cell response in a primary
      regressing human melanoma lesion.

PMID- 10064076
TI  - A MAGE-6-encoded peptide is recognized by expanded lymphocytes infiltrating a
      spontaneously regressing human primary melanoma lesion.
AB  - In recent years, experiments based on the in vitro stimulation of either
      autologous peripheral blood lymphocytes or tumor-infiltrating lymphocytes with
      melanoma cells have shown that distinct members of the large MAGE gene family
      encode tumor-associated antigenic peptides. However, little is still known about
      natural anti-MAGE responses in vivo. We have studied a case of spontaneously
      regressing human melanoma, hypothesizing that in this unique situation, the host
      immune system had developed an efficient cytotoxic T lymphocyte (CTL) response
      against the cancer cells. Amongst the dense tumor infiltrate, certain clonal
      populations of T cells were shown to be amplified, thereby suggesting that an
      antigen-driven selection had occurred at the tumor site. One of the expanded
      tumor-infiltrating lymphocytes was shown to be a Vbeta13+ CD8+ CTL displaying a
      strong and selective cytotoxic activity against the autologous melanoma cells.
      Here we show that this cytotoxic T cell clone recognizes a MAGE-6-encoded
      peptide. MAGE-6 is therefore the fourth gene of the MAGE family shown to encode
      antigenic peptide recognized by T cells. Together, these data provide further
      evidence that T cell responses against MAGE antigens may naturally develop in
      vivo.

PMID- 10064077
TI  - Naive cytotoxic T lymphocytes spontaneously acquire effector function in
      lymphocytopenic recipients: A pitfall for T cell memory studies?
AB  - Whether memory T cells require persisting antigen for their survival has been a
      matter of debate. One prominent view that memory T cells do not require
      persisting antigen is based in part on studies in which T cell populations have
      been transferred into antigen-free mice. To generate "space" recipients were
      often irradiated; the functional properties of the transfused T cells were then
      evaluated after prolonged periods. In this report we show that transferring
      cytotoxic T lymphocytes (CTL) into irradiated or T and B cell-deficient hosts
      results in their proliferation and a change of their activation state. Moreover,
      naive T cell receptor-transgenic CTL specific for the lymphocytic
      choriomeningitis virus glycoprotein spontaneously developed cytotoxic effector
      function under such conditions. Therefore, some of the conclusions based on
      transfer of T cell populations into irradiated recipients to investigate T cell
      memory may have to be reevaluated.

PMID- 10064078
TI  - CD40-deficient mice infected with the defective murine leukemia virus LP-BM5def
      do not develop murine AIDS but produce IgE and IgG1 in vivo.
AB  - CD40-deficient mice, when inoculated with the LP-BM5def murine retorvirus, become
      infected and show virus expression similar to wild-type mice. However, unlike the
      wild-type mice, CD40-deficient mice do not develop symptoms of immunodeficiency,
      lymphoproliferative disease and the typical histological changes in the lymphoid
      tissue. These results show that the CD40-CD40 ligand (CD40L) interaction in vivo
      is essential for anergy induction and the subsequent development of
      immunodeficiency and pathologic expansion of lymphocytes. Infected CD40-deficient
      mice and their littermates express a similar pattern of cytokine mRNA, which is
      not biased towards a Th2 phenotype. Nevertheless, hypergammaglobulinemia is
      induced in infected wild-type and CD40-deficient mice. Surprisingly, murine AIDS
      infection even induces IgE production in CD40-deficient mice in vivo. Our data
      demonstrate that antibody class switch to IgE and IgG1 can be induced by a
      retroviral infection in vivo even in the absence of CD40-CD40L interaction and an
      apparent switch to a Th2 cytokine production.

PMID- 10064079
TI  - Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1.
AB  - The individual role of tumor necrosis factor receptor 1 (TNFR1) and TNFR2
      signaling in experimental autoimmune encephalomeylitis (EAE) was investigated
      using mice lacking TNFR1 (TNFR1-/-), TNFR2 (TNFR2-/-) as well as double receptor
      (TNFR1/2-/-) and double ligand (TNF/LT alpha-/-) knockout mice. In wild-type (wt)
      mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 the
      clinical course is characterized by an acute disease onset with peak disease
      scores and a consecutive chronic phase lasting up to 60 days. Compared to control
      mice, TNF/LT alpha-deficient mice showed a significant delay in disease onset and
      a remarkable reduction in demyelination which was, however, associated with
      increased inflammation. In TNFR1-/- and TNFR1/2-/- mice, the disease course was
      comparable to TNF/LT alpha-deficient mice but rather monophasic and less severe
      at late time points. Likewise only minimal spinal cord demyelination became
      apparent. In contrast, the course of EAE in TNFR2-/- mice was severe and
      associated with remarkable demyelination. Taken together these findings define
      TNFR1 as crucial mediator in MOG-induced EAE and suggest a protective role for
      TNFR2 signaling in the clinical course of EAE.

PMID- 10064080
TI  - Selective expression of liver and activation-regulated chemokine (LARC) in
      intestinal epithelium in mice and humans.
AB  - The liver and activation-regulated chemokine (LARC), also termed MIP-3alpha and
      Exodus, is a novel human CC chemokine with a selective chemotactic activity for
      lymphocytes and dendritic cells. Here we describe genomic and cDNA clones
      encoding the murine orthologue of LARC (mLARC). The gene consists of four exons
      and three introns. The 5'-noncoding region of about 400 bp contains typical TATA
      and CAAT boxes but no other potential regulatory elements so far described. The
      cDNA encodes a CC chemokine of 97 amino acid residues with the highest homology
      to human LARC (64% amino acid identity). The 3'-noncoding region contains as many
      as five potential mRNA destabilization signals. mLARC was strongly and
      transiently induced in the murine monocytoid cell line J774 by lipopolysaccharide
      (LPS) but not by cytokines such as TNF-alpha, IFN-gamma, IL-1beta or IL-4. In
      normal mice, mLARC mRNA was expressed selectively in intestinal tissues such as
      small intestine and colon. Upon treatment with LPS, mLARC expression was enhanced
      in intestinal tissues and induced in some lymphoid tissues such as lymph nodes.
      Because of alternative splicing, there are two types of transcripts encoding
      mLARC and its variant mLARCvar with and without an N-terminal alanine in the
      mature protein, respectively. Both types of transcripts appeared to be expressed
      in various mouse tissues. In situ hybridization revealed that epithelial cells of
      intestinal tissues, especially those lining lymphoid follicles, expressed mLARC.
      Localization of LARC mRNA in epithelial cells was also demonstrated in a human
      appendix. Furthermore, mLARC was efficiently chemotactic for cells such as
      gammadelta type T cells in intestinal epithelium and naive B cells in Peyer's
      patches. Thus, in both humans and mice, LARC may be physiologically involved in
      formation and function of the mucosal lymphoid tissues by attracting lymphocytes
      and dendritic cells toward epithelial cells.

PMID- 10064081
TI  - Combined effects of IL-12 and IL-18 on the clinical course and local cytokine
      production in murine pulmonary infection with Cryptococcus neoformans.
AB  - We reported recently that interleukin (IL)-12 and IL-18 synergistically increased
      the fungicidal activity of mouse peritoneal exudate cells against Cryptococcus
      neoformans by inducing the production of interferon (IFN)-gamma by natural killer
      (NK) cells. To confirm these findings in vivo, we examined the effect of combined
      treatment using these two cytokines on the course of experimentally induced
      pulmonary and disseminated cryptococcosis in mice. IL-12 and IL-18 were used at
      subtherapeutic doses (0.005 and 2 microg/mouse/day, respectively). A single
      administration of either cytokine was not effective in protecting mice against
      the infection, while combined treatment significantly prolonged survival time of
      infected mice and reduced the lung and brain loads of organisms. These protective
      effects were associated with elevated IFN-gamma and reduced IL-4 levels in
      bronchoalveolar lavage fluid. Finally, depletion of NK and gammadelta T cells,
      but not of CD4+ T cells, by administration of specific antibodies, significantly
      reduced the production of IFN-gamma in lungs by IL-12/IL-18 treatment during the
      7 days of infection. Our results demonstrated that IL-12 and IL-18 protected mice
      against cryptococcal infection in a synergistic manner by enhancing the local
      production of IFN-gamma by NK and gammadelta T cells in the early phase of
      infection and by suppressing the production of IL-4 in lungs.

PMID- 10064082
TI  - Induction of IFN-gamma-producing CD4+ natural killer T cells by Mycobacterium
      bovis bacillus Calmette Guerin.
AB  - The CD4+ natural killer (NK)T cells in the liver are potent IL-4 producers and
      hence may promote Th2 cell development. Following Mycobacterium bovis bacillus
      Calmette Guerin (BCG) infection, IL-4-producing CD4+ NKT cells become
      undetectable in liver mononuclear cells of normal density (interface between 40
      and 70% Percoll) by flow cytometry. The present study shows that M. bovis BCG
      infection changes the density of liver CD4+ NKT cells and shifts cytokine
      production from IL-4 to IFN-gamma. The number of CD4+ NK1+ TCR
      alpha/beta(intermediate) cells increased in the low-density fraction (<40%
      Percoll density gradient) in parallel to the reduction of this cell population in
      the fraction of normal density. The number of IL-4-producing cells, however, was
      small and high frequencies of IFN-gamma-secreting cells were identified in the
      low-density fraction after TCR/CD3 ligation. Accordingly, selected low-density
      CD4+ NKT cells encompassed high numbers of IFN-gamma producers and minute numbers
      of IL-4-secreting cells. Induction of low-density CD4+ NKT cells by M. bovis BCG
      was abrogated by endogenous IL-12 neutralization which also caused increased
      bacterial growth in the liver. We assume that M. bovis BCG infection changes
      cytokine secretion by the CD4+ NKT cell population from IL-4 to IFN-gamma through
      IL-12 induction. Thus, CD4+ NKT cells may contribute to host resistance against
      intracellular bacteria prior to conventional IFN-gamma-producing Th1 cells.

PMID- 10064083
TI  - Identification of destabilizing residues in HLA class II-selected bacteriophage
      display libraries edited by HLA-DM.
AB  - HLA-DM (DM) functions as a peptide editor by catalyzing the release of class II
      associated invariant chain peptides (CLIP) and other unstable peptides, thus
      supporting the formation of stable class II-peptide complexes for presentation.
      To investigate the general features that determine the DM susceptibility of HLA
      DR1/peptide complexes, we generated a large DM-sensitive peptide repertoire from
      an M13 bacteriophage display library using a novel double selection protocol: we
      selected bacteriophage capable of binding to DR1 molecules and, subsequently, we
      enriched DR1-bound bacteriophage susceptible to elution by purified DM molecules.
      Sequence and mutational analyses of the DR1/DM double-selected peptides revealed
      that the amino acids Gly and Pro play a destabilizing role in the dissociation
      kinetics of DR1 ligands. This observation was confirmed also in natural peptide
      sequences such as CLIP 89-101, HA 307-319 and bovine collagen II (CII) 261-273.
      Our results demonstrate that DM susceptibility does not only depend on the number
      and nature of anchor residues, or the peptide length. Instead, less obvious
      sequence characteristics play a major role in the DM editing process and
      ultimately in the composition of peptide repertoires presented to T cells.

PMID- 10064084
TI  - Post-thymectomy autoimmune gastritis: fine specificity and pathogenicity of anti
      H/K ATPase-reactive T cells.
AB  - Thymectomy at day 3 of life (d3Tx) results in the development of organ-specific
      autoimmunity. We have recently shown that d3Tx BALB/c mice which develop
      autoimmune gastritis contain CD4+ T cells specific for the gastric parietal cell
      proton pump, H/K ATPase. Here, we demonstrate that freshly explanted gastric
      lymph node (LN) cells from d3Tx mice react significantly to the H/K ATPase alpha
      chain, but only marginally to the beta chain. Two H/K ATPase-reactive T cell
      lines were derived from the gastric LN of d3Tx mice. Both are CD4+, TCR
      alpha/beta-, and I-Ad restricted, and recognize distinct peptides from the H/K
      ATPase alpha chain. One cell line secretes Th1 and the other Th2 cytokines, but
      both are equally potent in inducing gastritis with distinct profiles of cellular
      infiltration in nu/nu recipient animals. Neither of the cell lines induced
      disease in normal BALB/c recipients and transfer of disease to nu/nu recipients
      was blocked by co-transfer of normal BALB/c spleen cells containing CD4+ CD25+
      cells. Although CD4+ CD25+ T cells are thought to emigrate from the thymus after
      day 3 of life, they could be identified in LN of 2-day-old animals. The capacity
      of CD4+ CD25+ T cells to abrogate the pathogenic activity in vivo of both
      activated Th1/Th2 lines strongly suggests that this suppressor T cell population
      may have a therapeutic role in other models of established autoimmunity. The
      availability of well-characterized lines of autoantigen-specific T cells should
      greatly facilitate the analysis of the mechanism of action and target of the CD4+
      CD25+ immunoregulatory cells.

PMID- 10064085
TI  - Differential induction of monocyte chemotactic protein-3 in mononuclear
      leukocytes and fibroblasts by interferon-alpha/beta and interferon-gamma reveals
      MCP-3 heterogeneity.
AB  - Monocyte chemotactic protein-3 (MCP-3) is a pluripotent CC chemokine, attracting
      most leukocytic cell types. With the use of a sensitive and specific ELISA, MCP-3
      was found to be inducible in fibroblasts and peripheral blood mononuclear cells
      (PBMC) by cytokines and cytokine inducers. MCP-3 production levels (1-10 ng/ml)
      were tenfold lower compared to those of MCP-1. In diploid fibroblasts,
      synergistic induction of MCP-3, but not of MCP-1, mRNA and protein was observed
      by combined treatment with IL-1beta and IFN-gamma. In PBMC, IFN-alpha and IFN
      beta (but not IFN-gamma), as well as measles virus and double-stranded RNA, were
      potent inducers of MCP-3, which suggests a role for this chemokine in an early
      stage of viral infections. In contrast, endotoxin failed to induce MCP-3
      production in fibroblasts and PBMC. Purification of MCP-3 from PBMC revealed
      biochemical heterogeneity. In monocyte chemotaxis and calcium mobilization
      assays, pure 11-kDa MCP-3 from PBMC showed similar potencies as MCP-3 from tumor
      cells. It was concluded that the induction of MCP-3 by IFN is regulated
      differently in fibroblasts and PBMC. In view of the multiple target cells for MCP
      3, local and strictly regulated chemokine production might be important to
      conduct selectively the immune response in infection or inflammation.

PMID- 10064086
TI  - Anergic T cells act as suppressor cells in vitro and in vivo.
AB  - The potential suppressive effects of allospecific anergic T cells were
      investigated both in vitro and in vivo. Allospecific T cells were rendered
      unresponsive in vitro using immobilized anti-CD3 mAb. These anergic T cells
      profoundly inhibited proliferation of responsive T cells in an antigen-specific
      manner. The observed inhibition did not appear to be due to the release of
      inhibitory cytokines in that secretion of IL-2, IFN-gamma, IL-4, IL-10 and TGF
      beta was greatly reduced following the induction of anergy, and neutralizing mAb
      specific for IL-4, IL-10 and TGF-beta failed to reverse the inhibition.
      Furthermore, the suppression mediated by anergic T cells required cell to cell
      contact. In vivo, adoptive transfer of anergic T cells into recipients of
      allogeneic skin grafts led to prolonged skin graft survival. Consistent with the
      lack of inhibitory cytokine production by the anergic cells, prolongation of skin
      allograft rejection was not influenced by the simultaneous administration of a
      neutralizing anti-IL-4 antibody. These results indicate that anergic T cells can
      function as antigen-specific suppressor cells both in vitro and in vivo.

PMID- 10064087
TI  - Salmonella vaccine carrier strains: effective delivery system to trigger anti
      tumor immunity by oral route.
AB  - Recombinant Salmonella strains expressing heterologous antigens can be delivered
      by oral route triggering the elicitation of efficient antigen-specific humoral, T
      helper and cytotoxic responses. The potential of attenuated Salmonella spp. to
      trigger anti-tumor immunity was evaluated for the first time by using beta
      galactosidase (beta-gal) as a model tumor-associated antigen (TAA). Beta-gal was
      expressed in a Salmonella typhimurium aroA vaccine carrier strain either
      constitutively or under the control of a promoter activated upon infection. Oral
      immunization with both vaccine prototypes resulted in the elicitation of beta-gal
      specific humoral and cell-mediated immunity. Although both strains were able to
      trigger antigen-specific CTL, responses were more efficient when the expression
      was controlled by the promoter activated upon infection. The anti-tumor efficacy
      of the stimulated response was validated by challenging vaccinated animals with
      an aggressive fibrosarcoma transfected with beta-gal, which operationally acts as
      a TAA. Both groups of vaccinated mice exhibited a significant reduction in tumor
      take and growth with respect to animals vaccinated with plasmidless carrier (p <
      0.05). However, the overall efficiency was better in the group in which beta-gal
      was controlled by the in vivo-activated promoter (85% versus 54%; p < 0.05).

PMID- 10064088
TI  - Differential immobilization and hierarchical involvement of chemokines in
      monocyte arrest and transmigration on inflamed endothelium in shear flow.
AB  - Monocyte extravasation into areas of inflammation involves sequential
      interactions of multiple adhesion molecules. However, differential contribution
      of chemokines produced by cytokine-stimulated endothelium and their receptors to
      leukocyte attachment and transmigration under flow conditions remains to be
      elucidated. The activation of endothelial cells with TNF-alpha up-regulated mRNA
      and protein expression of the CXC chemokine GRO-alpha and the CC chemokine
      monocyte chemotactic protein (MCP)-1, which act through the receptors CXCR2 and
      CCR2 expressed on monocytes, respectively. Whereas GRO-alpha was immobilized to
      endothelial cells via heparan sulfate proteoglycans, MCP-1 was secreted in a
      soluble form. Consequently, inhibition experiments with blocking peptide
      analogues and monoclonal antibodies revealed that GRO-alpha and its receptor
      CXCR2 but not MCP-1 and its receptors substantially contributed to conversion of
      rolling into firm, shear-resistant arrest of monocytes to TNF-alpha-stimulated
      endothelium in physiological flow. In contrast, MCP-1 and CCR2 but not GRO-alpha
      and CXCR2 mediated spreading, shape change and subsequent transendothelial
      migration, which was evident in flow but rarely in stasis and may thus require
      the establishment of a diffusible MCP-1 gradient. Differential patterns of
      presentation may determine a functional specialization and hierarchy of
      chemokines and their receptors in sequential steps of monocyte emigration on
      inflamed endothelium and shear flow.

PMID- 10064089
TI  - The immunoglobulin lambda light chain enhancer consists of three modules which
      synergize in activation of transcription.
AB  - V(D)J rearrangement, high level expression and somatic hypermutation of assembled
      Ig genes is tightly controlled by a number of regulatory sequence elements
      located in the vicinity of the J-, (D)-, and C-gene segments. During B cell
      maturation these elements become accessible to binding of trans-acting factors,
      reflecting the opening of the chromatin structure through an as yet unidentified
      mechanism. The mapping of regions of an altered chromatin structure (DNase I
      hypersensitivity) therefore is a powerful approach in identifying regulatory
      sequence elements. We here show that the human Ig lambda enhancer consists of
      three modules previously identified by us as DNase I-hypersensitive sites HSS-1, 
      2, and -3. The three sequence elements synergize in transcriptional activation of
      a reporter gene and together constitute a powerful tissue-specific enhancer which
      is a much stronger transcriptional activator than the kappa enhancers alone or in
      combination. We further show that the accessibility of the kappa and lambda
      enhancer elements for DNase I in the chromatin of a pre-B cell line (207)
      correlates with the transcriptional enhancer activities of kappa and lambda
      enhancer constructs. This finding is in support of an ordered model for Ig light
      chain activation (kappa before lambda).

PMID- 10064090
TI  - Is type II (non-insulin-dependent) diabetes mellitus not so "genetic" after all?

PMID- 10064091
TI  - Fatty acids, lipotoxicity and insulin secretion.

PMID- 10064092
TI  - Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal
      glucose tolerance--a population-based twin study.
AB  - To elucidate the relative importance of genetic and environmental factors on the
      development of Type II (non-insulin dependent) diabetes mellitus, we examined a
      sample of twins (n = 606) ascertained from the population-based Danish Twin
      Register. Based on a standard 75 g oral glucose tolerance test and current WHO
      criteria we identified 62 pairs in which one or both had Type II diabetes. The
      probandwise concordance (monozygotic: 0.50; dizygotic: 0.37) for Type II diabetes
      per se was not very different. When including the twins with impaired glucose
      tolerance (IGT), however, the probandwise concordance for abnormal glucose
      tolerance was significantly different between monozygotic (0.63) and dizygotic
      (0.43) twin pairs, (p < 0.01). These findings were supported by the heritability
      estimates for Type II diabetes per se (26%) and for abnormal glucose tolerance
      (61%). The metabolic variables, insulin resistance and insulin secretion, and
      anthropometric variables, body mass index and waist to hip ratio, known to be
      associated with the development of glucose intolerance had a heritability of 26,
      50, 80 and 6% respectively. This study confirms the notion of a multifactorial
      aetiology of Type II diabetes. It supports the contribution of non-genetic
      aetiological components in the development of Type II diabetes per se. The study
      also indicates a role for genes in the aetiology of abnormal glucose tolerance.
      We therefore propose that genetic predisposition is important for the development
      of abnormal glucose tolerance. Non-genetic factors, however, might play a
      predominant role in controlling whether a genetically predisposed individual
      progresses to overt Type II diabetes.

PMID- 10064093
TI  - Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial
      analysis.
AB  - To determine the concordance rate for Type II (non-insulin-dependent) diabetes
      mellitus in monozygotic twin pairs, initially ascertained discordant for
      diabetes, we carried out a prospective study on 44 non-diabetic subjects, each of
      whom had a sibling twin with diabetes (21 men, 23 women, median age 55 years,
      interquartile range 47-65). The subjects were referred as discordant for Type II
      diabetes. The twin pairs were part of the British Diabetic Twin Study and
      ascertained between May 1968 and January 1998. These subjects underwent an OGTT
      at time of referral and periodically thereafter. The mean follow-up was 8 years
      (range 0-18 years) and data were collected until January 1996. The percentage of
      twins who developed Type II diabetes was assessed by standard actuarial life
      table methods and the pairwise concordance rate, that is the proportion of
      concordant pairs over the sum of concordant and discordant pairs, was calculated.
      The observed rates of concordance for Type II diabetes at 1, 5, 10, and 15 years
      follow-up were 17, 33, 57, and 76%, respectively. The concordance rate for any
      abnormality of glucose metabolism (either Type II diabetes or impaired glucose
      tolerance) at 15 years follow-up was 96%. The concordance rate for Type II
      diabetes in monozygotic twins is very high even in twins initially ascertained
      discordant for diabetes.

PMID- 10064094
TI  - A new antidiabetic agent (JTT-501) rapidly stimulates glucose disposal rates by
      enhancing insulin signal transduction in skeletal muscle.
AB  - A newly synthesized antidiabetic agent, JTT-501 is an isoxazolidinedione rather
      than a thiazolidinedione. An oral dose of JTT-501 (100 mg x kg(-1) x day(-1))
      given to 12-week-old male Zucker fatty rats for 7 days led to the amelioration of
      both hyperinsulinaemia (40% of non-treated) and hypertriglyceridaemia (23% of non
      treated) as well as a 2.4-fold increased insulin sensitivity as determined by a
      euglycaemic insulin clamp. In our study, we further evaluated the acute effect of
      JTT-501 on both the glucose infusion rates (GIR) and insulin signalling in
      skeletal muscle. Male Sprague-Dawley (SD) rats aged 10 weeks were injected
      intravenously with JTT-501 (5 mg/kg) and then a euglycaemic insulin clamp was
      initiated and glucose infusion rates monitored for 150 min. We found that this
      treatment increased the glucose infusion rate by 33% during the last 30 min in SD
      rats. After the clamp had been initiated for 30 min, the insulin-stimulated
      phosphatidylinositol 3-kinase (PI3-kinase) activities co-immunoprecipitated with
      insulin receptor substrate 1 (IRS-1) were also enhanced, resulting in increased
      glycogen synthase activities in the soleus muscles. Treatment with JTT-501 also
      enhanced the phosphorylation of insulin receptors and insulin receptor-substrate
      1 rapidly as well as the phosphatidylinositol 3-kinase activities, which were
      stimulated by a bolus injection of insulin. Similarly, JTT-501 stimulated the
      glucose infusion rate by 30% and enhanced insulin signalling in Zucker fatty
      rats. In conclusion, a newly developed isoxazolidinedione, JTT-501, rapidly
      potentiates the insulin sensitivity of skeletal muscle by enhancing insulin
      signalling and could be useful for the treatment of insulin-resistant diabetic
      subjects.

PMID- 10064095
TI  - Leptin is suppressed during infusion of recombinant human insulin-like growth
      factor I (rhIGF I) in normal rats.
AB  - To examine whether insulin-like growth factor I (IGF I) or growth hormone (GH)
      influences leptin in vivo we measured leptin mRNA in epididymal fat pads and
      serum leptin of normal rats infused subcutaneously for 6 days with recombinant
      human (rh)IGF I (1 mg/day), rhGH (200 mU/day), or vehicle. In addition, we
      determined fat pad weight and food consumption as well as IGF I, insulin,
      glucose, non-esterified fatty acid (NEFA), glycerol, beta-hydroxybutyrate and
      triglyceride (TG) serum concentrations. Food intake was identical during all
      three treatments. RhIGF I but not rhGH raised IGF I serum concentrations, reduced
      fat pad weight (60.3 +/- 7.4% of control rats, p = 0.019), and suppressed leptin
      mRNA (38.8 +/- 11.9% of control rats, p = 0.002), serum leptin (51.6 +/- 10.5% of
      control rats, p = 0.0028) and serum triglycerides (39.3 +/- 8.0% of control rats,
      p = 2.6 x 10(-6)). Both rhIGF I and rhGH reduced non-esterified fatty acids
      (NEFA) (p = 0.00001 and 0.0007, respectively), whereas serum glycerol, beta-OH
      butyrate and glucose concentrations remained unchanged. Serum insulin
      concentrations during rhIGF I were lower than during rhGH infusion and correlated
      with leptin mRNA (r = 0.589, p = 0.016) and fat pad weight (r = 0.643, p =
      0.007). Reduction of adipose tissue mass and suppression of leptin by IGF I
      appear to be due to reduced circulating insulin leading to enhanced fat
      mobilization and NEFA oxidation as well as to increased gluconeogenesis from
      glycerol. In contrast, decreased NEFA concentrations during rhGH in the presence
      of unchanged fat pad weight, serum glycerol and triglycerides might result from
      more efficient re-esterification of released fatty acids within the triglyceride
      fatty acid cycle. The results also show that exogenously infused IGF I and GH act
      on lipid metabolism by different mechanisms and suggest an IGF-independent,
      probably direct, metabolic effect of GH. Finally, in agreement with previous
      studies in GH-infused hypophysectomized rats, it appears unlikely that GH
      regulates leptin in the rat.

PMID- 10064096
TI  - Alterations in platelet Ca2+ signalling in diabetic patients is due to increased
      formation of superoxide anions and reduced nitric oxide production.
AB  - Increased aggregation of platelets might contribute to the development of
      vascular complication in diabetes mellitus. In this study release of superoxide
      anions, intracellular Ca2+ signalling and nitric oxide formation stimulated by
      the receptor-dependent agonist adenosine 5 '-diphosphate (ADP) and the receptor
      independent stimulus thapsigargin, were compared in platelets isolated from
      patients with Type II (non-insulin-dependent) diabetes mellitus and healthy
      control subjects. Diabetes augmented intracellular Ca2+ release and Ca2+ entry to
      ADP by 40 and 44% (control subjects: n = 11; diabetic: n = 6), while the median
      effective concentration (EC50) of ADP to initiate Ca2+ signalling was similar in
      both groups. The effect of thapsigargin on Ca2+ concentration was increased by
      69% in diabetic patients (control subjects: n = 22; diabetic patients: n = 9). In
      addition, release of superoxide anions was 70% greater in diabetic patients
      (control subjects: n = 9; diabetic patients: n = 6). Treatment of platelets from
      control subjects with the superoxide anion-generating mixture xanthine oxidase
      and hypoxanthine or buthioninesulphoximine (BSO) mimicked the effect of diabetes
      on platelet Ca2+ signalling. The antioxidant glutathione normalized enhanced Ca2+
      response in the diabetic group (control subjects: n = 5: diabetic patients: n =
      6). Basal and thapsigargin-evoked nitric oxide synthase activity was reduced in
      the diabetic group by 85 and 64%, respectively (control subjects: n = 13;
      diabetic subjects: n = 13). The nitric oxide-donor 2-(N,N-diethylamino)
      diazenolate-2-oxide sodium (DEA/NO) normalized enhanced Ca2+ signalling in
      platelets preincubated with xanthine oxidase and hypoxanthine (n = 12) and in
      those from diabetics (control subjects: n = 6; diabetic patients: n = 6).
      Inhibition of nitric oxide synthase by N-nitro-L-arginine (L-NA) augmented
      thapsigargin-induced Ca2+ signalling by 51% (n = 8). These data indicate that in
      diabetes platelet Ca2+ signalling might be enhanced by excessive superoxide
      production and an attenuated negative direct or indirect feedback control by
      nitric oxide, due to its reduced production.

PMID- 10064097
TI  - Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed
      insulin response to glucose.
AB  - In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown
      to be predictive for progression to Type II (non-insulin-dependent) diabetes
      mellitus. These findings are often interpreted as early indicators of an impaired
      beta-cell function. The aim of our study was to assess the potential determinants
      of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study
      group consisted of 110 subjects, 45-74 years of age with mean 2 h plasma glucose
      concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance
      tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a
      priming infusion of 20% glucose solution, 150 mg/kg) was used to assess the beta
      cell function (time needed to reach the insulin peak) and insulin sensitivity
      (M/I value: glucose metabolised divided by insulin response, 150-180 min).
      Results showed that the intact-proinsulin:insulin ratio increased with increasing
      time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to
      reach the insulin peak < or = 5 min, 5 to 15 min, > 15 min; p < 0.05). The split
      proinsulin:insulin ratio showed a similar association with the time needed to
      reach the insulin peak. These associations were independent of age, sex, body
      mass index and waist:hip ratio. In conclusion, this study shows that relative
      hyperproinsulinaemia is associated with an impaired beta-cell function in a study
      group of subjects with impaired glucose tolerance selected after two oral glucose
      tolerance tests.

PMID- 10064098
TI  - Islet autoantibodies in cord blood from children who developed type I (insulin
      dependent) diabetes mellitus before 15 years of age.
AB  - Islet autoantibodies are early markers for Type I (insulin-dependent) diabetes
      mellitus. The aim of this study was to establish whether islet autoantibodies
      were present at birth in children who developed Type I diabetes before 15 years
      of age. Cord blood sera from 81 children who developed Type I diabetes between 10
      months and 14.9 years of age were tested for glutamic acid decarboxylase
      autoantibodies (GAD65Ab), islet cell antigen 512 autoantibodies (ICA512Ab),
      insulin autoantibodies (IAA) all by quantitative radioligand binding assays and
      islet cell autoantibodies (ICA) by indirect immunofluorescence. Cord blood sera
      from 320 randomly selected matched children were controls. The children who
      developed Type I diabetes had an increased frequency of cord blood islet
      autoantibodies compared with control subjects: Glutamic acid decarboxylase
      autoantibodies were detected in 6% (5/81) patients and 2% (5/320) control
      subjects (p = 0.03); islet cell antigen 512 autoantibodies in 5% (4/73) patients
      and 1% (4/288) control subjects (p = 0.06); insulin autoantibodies (IAA) in 0%
      (0/79) patients and 0.3% (1/320) control subjects (p = 0.36); and islet cell
      autoantibodies in 10% (8/81) patients compared with 0.6% (2/320) control subjects
      (p = 0.0001). Taken together, 17% (14/81) patients had one or more islet
      autoantibody compared with 4% (12/320) control subjects (p = 0.0001). Whereas
      none of the control children had more than one antibody, 4% (3/81) children who
      later developed Type I diabetes were double positive (p = 0.002). Although
      glutamic acid decarboxylase autoantibodies' concentrations in cord-blood
      correlated to those in the mothers' blood at the time of delivery, no
      corresponding correlation was found for the other two types of autoantibodies.
      The increased frequency of cord blood islet autoantibodies suggests that the Type
      I diabetes process could already be initiated in utero.

PMID- 10064099
TI  - Prolonged exposure of pancreatic beta cells to raised glucose concentrations
      results in increased cellular content of islet amyloid polypeptide precursors.
AB  - Most non-insulin dependent diabetic patients have amyloid deposits in their
      pancreatic islets. It is not known whether chronic hyperglycaemia contributes to
      the formation of amyloid fibrils from the islet amyloid polypeptide that is
      produced by the pancreatic beta cells. Since islet amyloid exhibits islet amyloid
      polypeptide precursors immunoreactivity, we examined whether sustained in vitro
      exposure to raised glucose increases the abundance of these precursors in human
      beta cells. After 6 days stimulation with 20 mmol/l glucose the cellular content
      of insulin but not islet amyloid polypeptide was decreased leading to an increase
      in the ratio of the latter over insulin (3.0 +/- 0.6 vs 1.8 +/- 0.3 after 6
      mmol/l glucose culture, p < 0.05). Similar changes occurred in rat beta cells
      cultured for 3 days in the presence of 20 mmol/l glucose plus 3-isobutyl-1
      methylxanthine. Western blot analysis of cellular islet amyloid polypeptide after
      prolonged exposure to high glucose indicated the presence of higher proportions
      of its precursor- and intermediate forms. In human beta cells cultured in 20
      mmol/l glucose, the major form corresponds to an intermediate species which
      exhibits an immunoreactivity for the N-flanking peptide, as is also the case in
      islet amyloid. We concluded that prolonged in vitro exposure of beta cells to
      raised glucose concentrations increases the relative proportion of islet amyloid
      polypeptide over insulin, as well as of its precursors over the mature form of
      islet amyloid polypeptide.

PMID- 10064100
TI  - Glucose induces early growth response gene (Egr-1) expression in pancreatic beta
      cells.
AB  - A copy deoxyribonucleic acid (cDNA) clone of the immediate early growth response
      gene, egr-1 (Krox-24, Zif268, NGFI-1), was isolated through subtractive
      hybridization screening to identify glucose-induced genes in pancreatic beta
      cells. Glucose rapidly and transiently induced egr-1 mRNA in the SV40-transformed
      murine beta-cell line, MIN6. Glucose also increased egr-1 mRNA expression in INS
      1, betaTC3 and RINm5F beta-cell lines, although with different kinetics.
      Expression of the 82 kDa Egr-1 protein was induced both in MIN6 cells stimulated
      with glucose in vitro and in primary rat islet cells stimulated in vivo or in
      vitro. This response is unique to beta cells since glucose did not affect egr-1
      expression in NIH-3T3 fibroblasts or glucose-sensitive hepatocytes. In beta cells
      egr-1 induction is specifically associated with insulin secretion, as it was not
      observed after stimulation with serum or insulin but was elicited by insulin
      secretagogues, including membrane depolarizing agents and cAMP agonists.
      Moreover, induction of egr-1 by glucose was inhibited by EDTA, indicating
      dependence on influx of extracellular Ca2+. Other immediate early response genes,
      c-fos and junB, were also induced following glucose stimulation with kinetics
      similar to egr-1, whereas c-jun and junD expression were not affected. Since the
      zinc-finger protein encoded by egr-1 is highly homologous to transcription
      factors that control expression of glucose-regulated genes in yeast, Egr-1 could
      mediate delayed adaptive responses of beta cells to sustained glucose stimulation
      through transcriptional regulation.

PMID- 10064101
TI  - Enhanced, unaltered and impaired nitric oxide-mediated endothelium-dependent
      relaxation in experimental diabetes mellitus: importance of disease duration.
AB  - Long-term diabetes mellitus is characterized by impaired endothelium-dependent
      relaxation. In contrast, there is limited information on endothelial function in
      the early stages of the disease. In this study, we evaluated endothelial function
      ex vivo at early, intermediate and later stages of streptozotocin (STZ)-induced
      diabetes mellitus. We also evaluated the contribution of various endothelium
      derived vasoactive factors at these stages of disease. In aortic rings contracted
      with norepinephrine, endothelium-dependent relaxation to acetylcholine was
      increased at 24 h following injection with streptozotocin compared with controls,
      normal after 1 and 2 weeks of disease or impaired at 8 weeks of disease.
      Endothelium-independent relaxation to nitroglycerin was unaltered at all stages.
      The enhanced relaxation at 24 h was mimicked in rings from alloxan-induced
      diabetic rats. Acute exposure of normal rings to streptozotocin in vitro caused
      no perturbation in acetylcholine-stimulated relaxation. Enhanced relaxation in
      diabetic rings at 24 h persisted in the presence of either indomethacin or
      tetraethylammonium. Acetylcholine-induced relaxation was blocked in both control
      and diabetic rings using L-nitroarginine but not by aminoguanidine. This suggests
      that the increased response was mediated by enhanced constitutive nitric oxide
      (NO). These studies show a triphasic response of increased, unaltered and
      impaired endothelium-dependent relaxation within the same model but dependent on
      the duration of disease. These studies could reconcile previous conflicting data
      in the literature and account for the observations of increases in tissue blood
      flow seen in early stages of experimental and human diabetes mellitus.

PMID- 10064102
TI  - Arterial compliance and distensibility are modulated by body composition in both
      men and women but by insulin sensitivity only in women.
AB  - Large artery stiffening could contribute to the development of cardiovascular
      disease. The aim of this study was to investigate associations between arterial
      stiffness and diameter with insulin sensitivity and body composition in healthy
      men and women. In healthy, young (< 41 years old), non-obese (BMI < 27 kg/m2) men
      (n = 17) and women (n = 17), we measured the arterial diameter, the distension,
      the distensibility coefficient and the compliance coefficient of the elastic
      common carotid and muscular femoral arteries with a non-invasive ultrasonographic
      method. We also assessed glucose uptake (by a euglycaemic hyperinsulinaemic clamp
      technique), total body fat and lean body mass (by bioelectrical impedance
      analysis) and abdominal subcutaneous and visceral fat area (by magnetic resonance
      imaging). In women, but not in men, the distension and distensibility and
      compliance coefficients of the femoral artery were negatively associated with
      insulin concentrations (beta = -0.62, p = 0.008; beta = -0.65, p = 0.005 and beta
      = -0.59, p = 0.01), and positively with glucose uptake (beta = 0.59, p = 0.02;
      beta = 0.68, p = 0.005 and beta = 0.54, p = 0.04). Associations with glucose
      uptake were independent of the mean arterial pressure and body composition. In
      men and women, arterial compliance was positively associated with fat mass
      variables, which were mediated by a strong association between the femoral artery
      diameter and lean body mass (beta = 0.80, p < 0.001) and between the common
      carotid artery diameter and visceral fat area (beta = 0.56, p = 0.001). We found
      an independent association between insulin resistance and arterial stiffness,
      which was more pronounced in women than in men.

PMID- 10064103
TI  - Peripheral blood mononuclear cells isolated from patients with diabetic
      nephropathy show increased activation of the oxidative-stress sensitive
      transcription factor NF-kappaB.
AB  - Increased oxidative stress and subsequent activation of the transcription factor
      NF-kappaB has been linked to the development of late diabetic complications. To
      determine whether oxidative stress dependent NF-kappaB activation is evident in
      patients with diabetic nephropathy we used an Electrophoretic Mobility Shift
      Assay based semiquantitative detection system which enabled us to determine NF
      kappaB activation in ex vivo isolated peripheral blood mononuclear cells. We
      examined 33 patients with diabetes mellitus (Type I and Type II). Patients with
      diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic
      Mobility Shift Assays and stronger immunohistological staining for activated NF
      kappaBp65 than patients without renal complications. NF-kappaB binding activity
      correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin
      plasma concentrations (r = 0.33), indicative for albuminuria associated
      endothelial dysfunction. In a 3 day intervention study in which 600 mg of the
      antioxidant thioctic acid (alpha-lipoic acid) per day were given to nine patients
      with diabetic nephropathy oxidative stress in plasma samples was decreased by 48%
      and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear
      cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in
      ex vivo isolated peripheral blood mononuclear cells of patients with diabetes
      mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation
      is at least in part dependent on oxidative stress since thioctic acid (alpha
      lipoic acid) reduced NF-kappaB binding activity.

PMID- 10064104
TI  - Circulating semicarbazide-sensitive amine oxidase is raised both in type I
      (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and
      even in childhood type I diabetes at first clinical diagnosis.
AB  - Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I
      (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is
      involved in the development of microvascular damage through its ability to
      convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen
      peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to
      be equally raised both in patients with Type I diabetes (n = 73) and Type II (non
      insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621
      +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in
      multiple regression analysis with HbA1c. Since the enzyme could protect the
      islets from the inhibitory effects of methylamine on insulin secretion, we also
      tested sera of 100 children, collected consecutively at first diagnosis of Type I
      diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly
      increased compared with serum values of 76 control (siblings) children (757 +/-
      300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study
      confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I
      diabetes and extends this finding to Type II diabetes as well as to childhood
      Type I at first clinical diagnosis. In the last case increased enzyme activities
      could serve to protect the islets from inhibitory effects of methylamine but
      cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the
      long run the increased enzyme activities could also contribute to vascular damage
      by direct cytotoxic action on endothelial cells, including increased oxidative
      stress and glycosylation of proteins.

PMID- 10064105
TI  - The W64R variant of the beta3-adrenergic receptor is not associated with type II
      diabetes or obesity in a large Finnish sample.
AB  - Recent studies have suggested an association between Type II (non-insulin
      dependent) diabetes mellitus-related phenotypes and a cytosine-to-thymidine
      substitution that results in the replacement of tryptophan by arginine at codon
      64 (Trp64Arg or W64R) of the beta3-adrenergic receptor gene. Here, we present the
      results of possibly the largest association study to date on the variant in a
      sample of 526 families with a total of 1725 subjects, 1053 of whom had Type II
      diabetes. Preliminary calculations suggested that we had excellent power to
      detect the moderate associations which were reported in previous studies. No
      associations were found between the W64R variant and the following phenotypes in
      our sample: Type II diabetes, age at diagnosis for Type II diabetes, measures of
      obesity, fasting glucose, fasting insulin, minimal model variables, and systolic
      and diastolic blood pressures. In the analysis of plasma lipids, we detected an
      association between the variant and HDL ratios (HDL cholesterol/total
      cholesterol) (p = 0.013), which remained significant even after adjusting for
      sex, affection status and age. Since W64R homozygotes (n = 11) had the highest
      HDL ratios, however, heterozygotes had the lowest and the wild-type subjects had
      intermediate values, we conclude that the W64R variant is unlikely to reduce HDL
      ratios in a dose-dependent, pathogenic manner.

PMID- 10064106
TI  - Implications of compound heterozygous insulin receptor mutations in congenital
      muscle fibre type disproportion myopathy for the receptor kinase activation.
AB  - We studied insulin receptor kinase activation in two brothers with congenital
      muscle fibre type disproportion myopathy and compound heterozygous mutations of
      the insulin receptor gene, their parents, and their unaffected brother. In the
      father who has a heterozygote Arg1174-->Gln mutation, in situ activation of the
      receptor kinase in skeletal muscle was reduced about 70%. Selection of only those
      receptors that bound to anti-phosphotyrosine antibody showed that these receptors
      had normal kinase activity and that the reduction in overall kinase activity was
      due to the inability of about 70% of the receptors to become insulin-dependently
      activated. The mother carries a point mutation at the last base pair in exon 17
      which, due to abnormal alternative splicing, could lead to normally transcribed
      receptor or truncated receptor lacking the kinase region. Kinase activation was
      normal in the mother's skeletal muscle, suggesting that virtually no truncated
      receptor was expressed. Receptor kinase activity was, however, reduced by 95 and
      91% in the compound heterozygous brothers. This suggests that the mother's
      mutated allele contributes little to the generation of functional receptor
      protein and that the receptors in the mother's skeletal muscle are transcribed
      almost exclusively from the non-mutated allele. The mutation in exon 17 could
      lead to reduced transcription or rapid degradation of a predominantly transcribed
      truncated gene product or both.

PMID- 10064107
TI  - An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan
      (CV12) acupoint in diabetic rats.
AB  - Acupuncture at the Zhongwan acupoint has been widely used in traditional Chinese
      medicine to relieve symptoms of diabetes mellitus. Our study investigated the
      effect on plasma glucose of electroacupuncture applied at the Zhongwan acupoint
      in rat diabetic models. Plasma concentrations of insulin, glucagon and beta
      endorphin- were also determined using radioimmunoassay. A decrease in plasma
      glucose was observed in rats after electroacupuncture (15 Hz, 10 mA) for 30 min
      at the Zhongwan acupoint. This was observed in normal rats and rat models with
      Type II (non-insulin-dependent) diabetes mellitus. No significant effect on
      plasma glucose was observed in rat models with Type I (insulin-dependent)
      diabetes mellitus: neither the streptozotocin (STZ)-induced diabetic rats nor the
      genetic (BB/W) rats. Further, the hypoglycaemic action of electroacupuncture
      stimulation disappeared in rats with insulin-resistance induced by an injection
      of human long-acting insulin repeated daily to cause the loss of tolbutamide
      induced hypoglycaemia. An insulin-related action can thus be hypothesised. This
      hypothesis is supported by an increase in plasma insulin-like immunoreactivity
      after electroacupuncture stimulation in normal rats. Participation of glucagon
      was ruled out because there was no change in plasma glucagon-like
      immunoreactivity resulting from electroacupuncture stimulation. In addition to an
      increase in plasma beta-endorphin-like immunoreactivity, the plasma glucose
      lowering action of electroacupuncture stimulation at Zhongwan acupoint was
      abolished by naloxone in a sufficient dose to block opioid receptors. Thus we
      suggest that electroacupuncture stimulation at the Zhongwan acupoint induces
      secretion of endogenous beta-endorphin which reduces plasma glucose concentration
      in an insulin-dependent manner.

PMID- 10064108
TI  - Measurement of glucose concentrations in rats: differences between glucose meter
      and plasma laboratory results.

PMID- 10064109
TI  - Temperature loggers are to be used to guarantee quality of insulin preparations.

PMID- 10064110
TI  - Muscle insulin resistance: a probable case of disuse of skeletal muscles.
      Lamarckism revisited.

PMID- 10064111
TI  - High affinity binding sites for proinsulin on human umbilical vein endothelial
      cells (HUVEC)

PMID- 10064112
TI  - Capsaicin-induced sensory denervation increases glucose elimination in rodents.

PMID- 10064113
TI  - Abnormal capacity to induce cholesterol efflux and a new LpA-I pre-beta particle
      in type 2 diabetic patients.
AB  - In this study, we first characterized the lipoprotein components of serum samples
      obtained from a group of well-controlled diabetic patients and from healthy
      subjects in fasting and postprandial states. We then explored some aspects of
      reverse cholesterol transport in the same population. Patients showed high levels
      of fasting triglycerides, postprandial triglyceride responses and LpC-III levels
      (3.18+/-0.86 vs 2.17+/-0.54 mg/dl, P < 0.001). There were also positive
      correlations between LpC-III and fasting triglycerides (r = 0.82, P < 0.001),
      total triglyceride area (r = 0.75, P < 0.001) and incremental triglyceride area
      (r = 0.54, P < 0.001). HDL-C and apo A-I were significantly decreased in diabetic
      patients due to a selective reduction in LpA-I subfraction, whose antiatherogenic
      role is generally accepted (37.4+/-8.0 vs 49.2+/-12.5 mg/dl, P < 0.001). In
      addition, HDL from patients proved to be triglyceride enriched and cholesteryl
      ester depleted, alterations which were further amplified in the postprandial
      state. The molar ratio HDL-C/apo A-I + apo A-II, already defined as a predictor
      of apo A-I fractional catabolic rate, was significantly diminished in the patient
      group (15.1+/-2.2 vs 20.8+/-3.3, P < 0.001), thus suggesting an accelerated
      catabolism of apo A-I. For the first time, we describe here the presence of a
      small apo A-I-containing particle, isolated by two-dimensional electrophoresis
      and characterized by immunoblotting, only in samples from diabetic patients. This
      particle that we named pre-beta0, has an apparent molecular weight of 40 kDa. As
      regards the capacity of serum samples to promote cholesterol efflux from
      [3H]cholesterol-labeled Fu5AH rat hepatoma cells, patient samples were found to
      induce significantly lower cholesterol efflux than controls only in the
      postprandial state (21.2+/-3.3 vs 23.8+/-1.8%, P = 0.012). The presence of pre
      beta0 in samples from diabetic patients might therefore be associated to an
      altered capacity of these serum samples to promote cellular cholesterol efflux.
      Overall, these abnormalities may contribute to a delay in the reverse cholesterol
      transport pathway in type 2 diabetic patients.

PMID- 10064114
TI  - Automated and simultaneous identification of microsatellite instability by
      fluorescence-based polymerase chain reaction (PCR) in four loci.
AB  - Genomic instability is sometimes due to impairment of DNA repair systems, which
      results in a change in the number of microsatellite repeats in tumor cells,
      produced by slippage during DNA replication. Such abnormal repeats are manifested
      as microsatellite instability (MSI). We have devised a simple assay using four
      color fluorescence for the detection of MSI by an automatic sequencer. Using this
      method, MSI and loss of heterozygosity (LOH) at four microsatellite loci can be
      identified simultaneously. We have also developed an algorithm and software for
      automated analysis of MSI and LOH with this method. Using our method for the
      detection of MSI in four microsatellite loci and the algorithm and software that
      we developed, 18 (94.7%) of 19 patients with hereditary nonpolyposis colorectal
      cancer (HNPCC), meeting the Amsterdam Minimum Criteria, were found to exhibit
      MSI.

PMID- 10064115
TI  - Quanititation of gene expression by means of HPLC analysis of RT-PCR products.
AB  - A method for the quantitative analysis of specific mRNA species by reverse
      transcription-polymerase chain reaction (RT-PCR) and subsequent detection of
      products by means of ion-pair reversed-phase high-performance liquid
      chromatography (IP-RP-HPLC) on alkylated micropellicular polystyrene
      divinylbenzene particles has been developed. For RT-PCR, we used the EZrTth RNA
      PCR kit (Perkin Elmer). This method allows reverse transcription and
      amplification of specific target mRNA in a single reaction tube. RT-PCR products
      were analyzed qualitatively and quantitatively by means of IP-RP-HPLC and UV
      detection at 254 nm. The enzymatic amplification combined with chromatographic
      separation and UV detection permitted high precision (and intra assay CV < 10%),
      with good practicability (two pipetting steps only). A total RNA preparation of a
      tissue that highly expressed the sequence of interest and that was stored in
      multiple aliquots, was diluted to give a standard curve. This external standard
      curve was used to define when samples have to be diluted, i.e., when the signal
      is in the plateau phase of amplification. The validity of the method is
      demonstrated with the example of human retinoic acid receptor mRNA.

PMID- 10064116
TI  - Carnitine homeostasis in patients with rheumatoid arthritis.
AB  - Myopathy is a frequent finding in patients with rheumatoid arthritis (RA). Since
      carnitine is important for skeletal muscle energy metabolism, carnitine
      metabolism was investigated in patients with RA and myopathy. Muscle strength was
      estimated by determination of a muscle strength index (MSI) which is derived from
      isometric measurements of muscle strength at knees and elbows. Carnitine was
      determined by a radioenzymatic method and 3-methylhistidine by high-performance
      liquid chromatography. In comparison to control subjects, patients had a reduced
      MSI. Both the 24-h creatinine and 3-methylhistidine excretions were reduced in
      patients. The plasma carnitine pool was not different between patients and
      control subjects, except for a higher long-chain acylcarnitine concentration in
      patients. Urinary excretion of carnitine was decreased in patients, also after
      normalization for body weight. Accordingly, renal carnitine clearance and
      excretion fraction were both decreased in patients. Skeletal muscle free- and
      total carnitine levels were increased in patients, whereas the long-chain
      acylcarnitine content was markedly decreased. The total skeletal muscle carnitine
      content showed a negative correlation with the MSI and no association with
      disease activity. Carnitine deficiency does not explain reduced skeletal muscle
      strength in patients with RA. Decreased renal carnitine excretion in patients is
      most likely due to reduced carnitine biosynthesis, leading to more efficient
      tubular carnitine reabsorption for maintaining the carnitine body stores.

PMID- 10064117
TI  - Screening of urine by one-dimensional and pulsed-field gradient two-dimensional
      1H NMR spectroscopy: intoxication by propylene glycol in an infant patient.
AB  - 1H NMR spectroscopy is a promising method for the analysis of physiological
      fluids in clinical medicine. In the course of screening the urine of patients by
      1D- and pulsed-field gradient 2D 1H NMR spectroscopy at 500 MHz, we encountered a
      case with a very high excretion of propylene glycol compared to others who
      received similar doses of the medication. In this case, the propylene glycol was
      scarcely metabolized by the patient. Propylene glycol is widely used as a safety
      material which is transformed into pyruvate and lactate in the healthy body. In
      this paper, we discuss how NMR spectroscopy can be a useful method for screening
      a patient intoxicated with propylene glycol.

PMID- 10064118
TI  - Urinary excretion of the vitronectin receptor (integrin alpha V beta 3) in
      patients with Fabry disease.
AB  - A renal disorder is one of the important manifestations of Fabry disease, but the
      details of the pathogenesis have not been clarified yet. We examined the
      possibility that the vitronectin receptor (VNR, integrin alpha V beta 3), one of
      the integrins, is involved in the progression of the renal injury in Fabry
      disease. We measured the urinary excretion of beta 3 originating from VNR in
      Fabry patients by immunoblotting analysis and enzyme-linked immunosorbent assay
      (ELISA). Immunofluorescent microscopic analyses for VNR and globotriaosylceramide
      were performed on urinary sediments from Fabry patients. Furthermore, beta 3 and
      vitronectin in kidney tissues were analyzed immunohistochemically. Immunoblotting
      analysis and ELISA showed that the urinary excretion of beta 3 originating from
      VNR was significantly increased in the Fabry group compared with both the
      pathological and healthy control groups. Immunofluorescent microscopy revealed
      the expression of VNR and accumulation of globotriaosylceramide in urinary
      sediments from the Fabry patients. Increased expression of beta 3 was observed in
      glomerular epithelial cells, and in Bowman's capsular epithelial layer and
      tubular cells, and the amount of vitronectin was moderately increased in the
      kidney tissues from the Fabry patients. The urinary excretion of VNR was
      increased, and the expression of VNR was observed in Fabry kidney tissues. The
      expression of VNR may be involved in the progression of the renal injury in this
      disease.

PMID- 10064119
TI  - Measurements of urinary nonisomerized form of type I collagen degradation
      products (alpha-CTx) in aging, menopause, and osteoporosis with fractures.
AB  - We have evaluated the effect of aging, menopause, and osteoporosis on the
      measurements of urinary nonisomerized form of type I collagen degradation
      products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144
      postmenopausal healthy women, 74 patients with vertebral fractures and 61
      patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age
      related changes of alpha-CTx in healthy females show that the values were
      extremely high before the age of 16 years and decreased between ages 16 and 29,
      and that after the age of 40 years, the values tended to increase and to vary
      widely with age. In menopause, alpha-CTx in postmenopausal subjects was
      significantly higher than those in premenopausal subjects. There was no
      significant correlation between alpha-CTx and years since menopause in 102
      postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher
      than those in the postmenopause group, but not significantly. Alpha-CTx in the
      hip fracture group were significantly higher than those in postmenopause and
      vertebral fracture groups. In age-matched comparisons, the values of the patients
      with vertebral fracture and the patients with hip fracture were significantly
      higher than those of corresponded age-matched postmenopausal women. Alpha-CTx
      well reflects an increase of bone resorption associated with bone modeling at
      childhood and high bone resorption after the menopause and higher bone resorption
      in osteoporotic patients with fractures.

PMID- 10064120
TI  - Magnetic resonance spectroscopy of serum and acute-phase proteins revisited: a
      multiparametric statistical analysis of metabolite variations in inflammatory,
      infectious and miscellaneous diseases.
AB  - Proton MR spectra and biochemical assays have been recorded on the sera of 40
      patients and ten controls in order to document the correlation between
      spectroscopic and biochemical variations in selected pathologies (cancer,
      inflammatory and infectious diseases, diabetes). N-acetyl proton resonances are
      essentially generated by the N-acetyl residues of the glucidic moieties borne by
      the most abundant acute-phase proteins (alpha1-acid glycoprotein, alpha1
      antitrypsin and haptoglobin). These resonances are not correlated to
      immunoglobulins A, G and M levels. Principal component analysis shows that
      variations in spectroscopic and biochemical data are independent markers of the
      inflammatory status of patients but no additional sensitivity or specificity is
      obtained when the two sets of data are combined.

PMID- 10064121
TI  - Indirect reference limits estimated from patients' results by three mathematical
      procedures.
AB  - Presently, only a few clinical laboratories produce their own reference values,
      while the great majority use reference intervals reported in the literature. An
      alternative to this unsatisfactory situation is to estimate indirect reference
      limits by means of mathematical/statistical procedures from patients' results
      obtained routinely in the laboratory. The procedures of Bhattacharya (A simple
      method of resolution of a distribution into Gaussian components. Biometrics
      1967;23:115-135) Martin et al. (Reference values based on populations accessible
      to hospitals. In: Grasbeck R, Alstrom T, editors. Reference Values in Laboratory
      Medicine. Chischester: Wiley, 1981:233-262) and Kairisto et al. (Generation of
      reference values for cardiac enzymes from hospital admission laboratory data. Eur
      J Clin Chem Clin Biochem 1994;32:789-796) were applied to 14 biochemical
      quantities. In order to verify these procedures, the indirect reference limits
      obtained from patients' results were validated by statistical comparison with
      reference limits estimated from a reference sample according to recommendations
      of the International Federation of Clinical Chemistry (IFCC). Calculated indirect
      reference limits for most quantities studied were reliable, but indirect
      reference limits for bilirubins and potassium ion substance concentrations,
      alanine aminotransferase, and aspartate aminotransferase catalytic concentrations
      in serum were not suitable. We conclude that indirect reference limits can be
      obtained from patients' results by all procedures studied when skewness and
      kurtosis of mixed distribution are not too large, but other factors also seem to
      have an influence on the reliability of these procedures.

PMID- 10064122
TI  - Distribution of serum creatine kinase activity in young healthy persons.
AB  - The normal distribution of serum creatine kinase (CK) was determined in 428 men
      (mean age = 21.5) and 540 women (mean age = 20.2). The bootstrap method was
      employed to obtain statistical parameters of CK reference range and correlations
      with physical activity habits, BMI, cigarette smoking and alcohol consumption. CK
      distribution was non-Gaussian and skewed toward the higher values; 18.9% of the
      men and 4.6% of the women had values above the upper reference limits defined for
      the commercial assay kit. The median 97.5 percentile value was 532 u/l for men
      and 248 u/l for women (95% confidence interval of 384-738 u/l and 184-340 u/l,
      respectively). A significant correlation was found only between CK and alcohol
      consumption in men. Myoglobin level in a representative group of subjects
      correlated well with CK activity for both genders. Our findings define the range
      of CK values in a healthy, young, heterogeneous population. We suggest that only
      CK levels above the determined 97.5 percentile should warrant further clinical
      investigation.

PMID- 10064123
TI  - Proton nuclear magnetic resonance spectroscopy of urine for rapid multicomponent
      analysis of intraoperative cellular metabolites.
AB  - We serially measured the proton nuclear magnetic resonance spectra of the urine
      of intraoperative patients over time to assess their potential use for rapid
      multicomponent analysis of cellular metabolites. Within a few minutes, the
      spectra provided signals of many low molecular weight urinary metabolites,
      including amino acids, ketone bodies, lactate, and glucose. The proton magnetic
      resonance spectra of the urine of most of the intraoperative patients showed
      large increases in urinary excretion of alanine, ketone bodies, and lactate
      and/or glucose, confirming alterations in energy substrate-endocrine
      relationships during the perioperative period. These metabolic changes appeared
      to be roughly proportional to the degree of surgical stress, but they were not
      consistent among patients who underwent the same operation. The study suggests
      that routine intraoperative metabolic monitoring is necessary to prevent critical
      metabolic disorders and that proton nuclear magnetic resonance spectroscopy of
      urine may meet this need by allowing rapid multicomponent analysis of cellular
      metabolites.

PMID- 10064124
TI  - Determination of potassium flux activity of viable human erythrocytes by
      measuring the release-influx ratio.
AB  - A simple and convenient method to determine the K+-flux activity of viable human
      erythrocytes was developed. Erythrocyte suspensions were incubated at 4 degrees C
      for 24 h to induce K+-release (deltaKr) and then at 37 degrees C for 3 h to
      influx K+ into erythrocytes (deltaKi). A straight-line relationship between K+
      release-influx ratio and ouabain-induced K+-efflux from erythrocytes indicated
      that deltaKi/deltaKr ratio or the K+-flux activity was reflected predominantly by
      Na+/K+-exchanging ATPase activity. Using this method, K+-flux activity of
      erythrocytes in the young and the aged subjects was measured. The mean
      deltaKi/deltaKr ratio of the aged subjects was decreased significantly. This
      method of measuring deltaKi/deltaKr ratio is useful for the evaluation of K+-flux
      activity of viable erythrocytes.

PMID- 10064125
TI  - Evaluation of mutation screening by heteroduplex analysis in acute intermittent
      porphyria: comparison with denaturing gradient gel electrophoresis.
AB  - Acute intermittent porphyria is the major autosomal dominant form of acute
      hepatic porphyrias. The disease is due to mutations in the gene encoding for
      porphobilinogen deaminase (PBGD). Many different strategies have been developed
      to screen for mutations. However the high prevalence (0.6 per thousand) of PBGD
      gene defect, the large allelic heterogeneity of mutations (n = 130), and the
      limitations of the PBGD enzymatic assay for asymptomatic patients' detection,
      require for diagnosis an efficient and easy to handle strategy for locating
      mutations within the PBGD gene. In a recent study the sensitivity of the
      denaturing gradient gel electrophoresis (DGGE) technique was 100%. However DGGE
      requires the preparation of gradient gels and the use of primers with long GC
      clamps; thus alternative methods should be preferable in the clinical laboratory.
      We have compared the detection rate of DGGE with heteroduplex analysis (HA) using
      16 characterized PBGD gene mutations. Six different HA conditions were used to
      determine the efficiency of the method, including: (1) MDE (mutation detection
      enhancement) gel concentration; (2) addition of urea and sodium dodecyl sulfate
      (SDS); (3) radioactive labelling. The sensitivity of each HA condition varied
      from 31 to 81% vs. 100% in DGGE analysis. HA using 1 x MDE with 15% urea with or
      without 0.55% SDS was the most sensitive condition. This first comparative study
      of DGGE and HA mutation screening methods suggests that DGGE is a more sensitive
      screening assay than optimized HA. However, because of its simplicity HA should
      be considered as an efficient alternative mutation screening method.

PMID- 10064126
TI  - Urinary bone resorption markers in monitoring treatment of symptomatic
      osteoporosis.
AB  - We have studied the clinical usefulness of urinary bone resorption markers in
      postmenopausal women with symptomatic osteoporosis. The study design is a
      randomised double-blind placebo controlled study, in which the subjects were
      daily treated for 24 months either with a hormone analogue (2.5 mg Livial,
      generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14,
      age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n =
      19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone
      resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD)
      and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type
      I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the
      urine assay results were calculated per mmol creatinine. All the resorption
      markers decreased during the two-year study period in both groups. The Z scores
      (discriminating power, i.e. ability of the different tests to distinguish the
      hormone treated subjects from the placebo treated subjects) for HOP and PYD were
      rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the
      two treatment groups were statistically significant for DPD at 12 and 24 months
      of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45
      1.90. NTx showed the most prominent decrease from the beginning of the study
      especially in the hormone treatment group: the differences between the two
      treatment groups were statistically highly significant for NTx already at 6
      months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11
      3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the
      lumbar spine and femoral neck did not show statistically significant differences
      between the two treatment groups throughout the two-year study period. After 2
      years there was, however, a significant increase in bone density both in the
      spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the
      women with hormone treatment. In the control group a significant increase (+
      5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.)
      in the femoral neck was observed. We suggest that measurement of urinary cross
      linked peptides derived from Type I collagen (NTx and DPD) might be a useful
      biochemical method of observing the positive clinical effect (i.e. reduction in
      bone resorption) following hormone replacement therapy in postmenopausal fracture
      patients.

PMID- 10064127
TI  - Decreased neutrophil antioxidative enzyme activities and increased lipid
      peroxidation in hyperlipoproteinemic human subjects.
AB  - Neutrophils have the capacity to produce free radicals. Free radicals are
      associated with hyperlipoproteinemia and atherosclerotic processes. For this
      reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px),
      glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid
      reactive substances (TBARS), as an index of lipid peroxidation, have been studied
      in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid
      parameters including triglycerides, total cholesterol, plasma TBARS, HDL
      cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty
      subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40
      normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were
      included in the study. Neutrophils were isolated by Percoll gradient
      centrifugation from venous blood samples. Methods used were as follows: INT
      method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and
      GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase,
      and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil
      SOD, GSH-Px, and catalase activities were found to be significantly low in the
      hyperlipoproteinemic group compared with the normolipoproteinemic group. GR
      activity did not differ between both groups. The mean TBARS level in the
      neutrophil fraction was found to be significantly higher in hyperlipoproteinemics
      than in that of the normolipoproteinemics. It was concluded that decreased
      neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to
      insufficient detoxification of free radicals produced in these cells and
      contribute to increased lipid peroxidation.

PMID- 10064128
TI  - Expression of a liver/bone-intestinal hybrid of alkaline phosphatase in
      neutrophils of Down's syndrome patients.

PMID- 10064129
TI  - Uptake of [3H]-fosfomycin into cells of enterohemorrhagic Escherichia coli O157
      and E. coli non-O157.

PMID- 10064130
TI  - False-negative rapid plasma reagin circle card test.

PMID- 10064131
TI  - Proto-oncogenes, unlike 'harmless' genes, tend to be dispersed in the human
      genome: selection against out-of-register recombination?

PMID- 10064132
TI  - The human H2A and H2B histone gene complement.
AB  - Sequences and expression patterns of newly isolated human histone H2A and H2B
      genes and the respective proteins were compared with previously isolated human
      H2A and H2B genes and proteins. Altogether, 15 human H2A genes and 17 human H2B
      genes have been identified. 14 of these are organized as H2A/H2B gene pairs,
      while one H2A gene and three H2B genes are solitary genes. Two H2A genes and two
      H2B genes turned outto be pseudogenes. The 13 H2A genes code for at least 6
      different amino acid sequences, and the 15 H2B genes encode 11 different H2B
      isoforms. Each H2A/H2B gene pair is controlled by a divergent promoter spanning
      300 to 330 nucleotides between the coding regions of the two genes. The highly
      conserved divergent H2A/H2B promoters can be classified in two groups based on
      the patterns of consensus sequence elements. Group I promoters contain a TATA box
      for each gene, two Oct-1 factor binding sites, and three CCAAT boxes. Group II
      promoters contain the same elements as group I promoters and an additional CCAAT
      box, a binding motif for E2F and adjacent a highly conserved octanucleotide
      (CACAGCTT) that has not been described so far. Five of the 6 gene pairs and 4
      solitary genes with group I promoters are localized in the large histone gene
      cluster at 6p21.3-6p22, and one gene pair is located at 1q21. All group II
      promoter associated genes are contained within the histone gene subcluster at
      D6S105, which is located at a distance of about 2 Mb from the major subcluster at
      6p21.3-6p22 containing histone genes with group I promoters. Almost all group II
      H2A genes encode identical amino acid sequences, whereas group I H2A gene
      products vary at several positions. Using human cell lines, we have analyzed the
      expression patterns of functional human H2A/H2B gene pairs organized within the
      two histone gene clusters on the short arm of chromosome 6. The genes show
      varying expression patterns in different tumor cell lines.

PMID- 10064133
TI  - Efficient control of raf gene expression by CAP and two Raf repressors that bend
      DNA in opposite directions.
AB  - The plasmid-borne raf operon of Escherichia coli encodes proteins involved in the
      uptake and utilisation of the trisaccharide raffinose. The operon is subject to
      dual regulation; to negative control by the binding of RafR repressor to twin
      operators, O1 and O2, and to positive control by the cAMP-binding protein, CAP.
      We have identified the CAP binding site (CBS) as a 22 bp palindromic sequence
      with incomplete dyad symmetry by deletion analysis, DNasel footprinting and
      electrophoretic mobility shift assays (EMSA) of CAP-DNA complexes. The CBS is
      centred 60.5 bp upstream of the transcription start point and partially overlaps
      O1. In vivo, CAP increases rafA (alpha-galactosidase) gene expression up to 50
      fold. The 28 bp spacing between the centres of CBS and the - 35 box is essential,
      since insertions of 4, 8, 12 or 16 bp completely eliminated rafA gene expression.
      In vitro binding studies revealed that the CBS, O1 and O2 sites, can be
      simultaneously occupied by their cognate proteins. However, no cooperativity
      between binding of CAP and RafR was detected. EMSA with circularly permuted DNA
      fragments demonstrated that CAP and RafR proteins bend raf promoter (rafP) DNA by
      75 degrees +/- 5 degrees and 95 degrees +/- 5 degrees, respectively, in opposite
      directions. Among sugar catabolic operons, the compact arrangement of three
      protein-binding sites, a CBS and two operators bounding the - 35 promoter box, is
      unique and provides a sensitive and highly efficient device for transcriptional
      control.

PMID- 10064134
TI  - Molecular models of acidic peptides from pea bud chromatin and seminal plasma.
      Divalent cations-mediated interaction with DNA.
AB  - Small acidic peptides have been isolated from biological fluids (blood and
      seminal plasma) and from chromatin of several tissues. Their biological activity
      is related to the control of cell growth and gene expression. This work is an
      approach to the study of peptide structure-function relationship. Purified
      fractions from seminal plasma and pea bud chromatin were subjected to fast ion
      bombardment mass spectrometry. The results obtained were analyzed according to
      biochemical characteristics of the peptides studied and some possible molecular
      models have been designed. Two of the proposed sequences were synthesized and
      their biological activity assayed in cells and cell-free systems. The results
      demonstrate that the synthetic peptides are able to bind to DNA in the presence
      of divalent cations (Mg2+, Fe2+, Cu2+) with consequent inhibition of DNA
      transcription.

PMID- 10064135
TI  - Cytidine triphosphate synthase activity and mRNA expression in normal human blood
      cells.
AB  - Cytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine
      nucleotide anabolic pathways. The activity of this enzyme is elevated in various
      malignancies including acute lymphocytic leukemia (ALL). In this study we
      investigated the activity of CTP synthase in various human blood cells isolated
      from healthy volunteers by density centrifugation and elutriation centrifugation.
      We also investigated the mRNA expression of CTP synthase in lymphocytes and
      monocytes. The highest activity of CTP synthase was found in thrombocytes (6.48
      nmol CTP x mg(-1) x h(-1)), followed by that of monocytes (2.23), lymphocytes
      (1.69), granulocytes (0.52) and erythrocytes (0.42). The activity of CTP synthase
      in whole blood samples was at an intermediate level (1.27). The mRNA expression
      of CTP synthase in monocytes was comparable to that observed in lymphocytes.

PMID- 10064136
TI  - Studies with lysine N6-hydroxylase. Effect of a mutation in the assumed FAD
      binding site on coenzyme affinities and on lysine hydroxylating activity.
AB  - The proposed FAD binding site of L-lysine N6-hydroxylase (EC 1.14.13.99) exhibits
      an unusual proline in a position where a highly conserved glycine is found in
      other FAD dependent hydroxylases. We have studied the role of this proline by
      mutating it to glycine in [P14G]aerA, which was expressed in Escherichia coli M15
      2 and purified to homogeneity. The mutation has marked effects on the affinities
      of the cofactors FAD and NADPH as well as the substrate, lysine. Compared to the
      wild-type enzyme, the activity vs. pH profile of the mutant protein indicates a
      shift of the apparent pK'(a)s (7.8 and 8.7 for wild-type and 6.8 and 7.7 for the
      P14G-mutant enzyme) and of the activity maximum (pH 8 for wild-type and pH 7 for
      the P14G-mutant enzyme). While the activity of the mutant enzyme is much lower
      under conditions found to be optimal for the wild-type enzyme, adjustment of
      substrate and cofactor concentrations and pH leads to comparable activities for
      the mutant enzyme. These results suggest that the proline fulfils an important
      structural role in the proposed FAD binding site.

PMID- 10064137
TI  - The recombinant thermosome from the hyperthermophilic archaeon Methanopyrus
      kandleri: in vitro analysis of its chaperone activity.
AB  - The archaeon Methanopyrus kandleri is the most thermophilic methanogen presently
      known. It contains a chaperonin (thermosome) which represents a 951 kDa homo
      hexadecameric protein complex with NH4+-dependent ATPase activity. Since its
      synthesis is not increased upon heat shock, we set out to test its chaperone
      function. In order to obtain the chaperonin in amounts sufficient for functional
      investigations, the gene encoding the 60 kDa subunit was expressed in E. coili
      BL21 (DE3) cells. Purification yielded soluble, high-molecular-mass double-ring
      complexes, indistinguishable from the natural thermosome. In order to study the
      functional properties of the recombinant protein complex, pig citrate synthase,
      yeast alcohol dehydrogenase, yeast alpha-glucosidase, bovine insulin, and
      Thermotoga phosphoglycerate kinase were used as model substrates. The results
      demonstrate that the recombinant M. kandleri thermosome possesses a chaperone
      like activity in vitro, inhibiting aggregation as the major off-pathway-reaction
      during thermal unfolding and refolding of proteins after chemical denaturation.
      However, the chaperonin only forms dead-end complexes with its non-native
      substrates, no release is detectable at temperatures between 25 and 60 degrees C.

PMID- 10064138
TI  - Not more than three tissue kallikreins identified from organs of the guinea pig.
AB  - The large and varied multigene families of tissue kallikreins of rat and mouse
      are considered to selectively release as many bioactive peptides. In order to
      determine whether a similar family of enzymes is expressed in the organs of the
      guinea pig purification studies were performed. Tissue kallikreins from the
      submandibular gland, coagulating gland/prostate complex and the pancreas were
      separated by affinity chromatography on benzamidine-Sepharose. Amino-terminal
      sequences, the patterns of hydrolysis rates of a number of peptide p
      nitroanilides, inactivation rates by active site-directed irreversible
      inhibitors, specific kininogenase activities and types of kinin released were
      used to probe the identity of the isolated enzymes. Guinea pig tissue kallikreins
      1 and 2 have been reported previously. In the present study we have identified a
      third type, designated tissue kallikrein 1a because of its sequence similarity to
      kallikrein 1, which differs from the latter in the catalytic properties. The
      inferred occurrence of not more than two or three independent tissue kallikrein
      genes in the guinea pig contrasts with the varied family of enzymes expressed by
      the large number of such genes present in rats and mice. Expression in the guinea
      pig (and also in humans) of only a small number of tissue kallikreins makes
      specific processing of a multitude of biologically active peptides by such
      enzymes unlikely.

PMID- 10064139
TI  - Activation of protein C by arginine-specific cysteine proteinases (gingipains-R)
      from Porphyromonas gingivalis.
AB  - In order to determine the effect of bacterial proteinases on activation of the
      protein C system, a negative regulator of blood coagulation, two arginine
      specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, a
      causative bacterium of adult periodontitis, were examined. Each enzyme activated
      human protein C in a dose- and incubation time-dependent manner. Interestingly,
      the form of enzyme being composed of a non-covalent complex containing both
      catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more
      efficiently than RgpB which contained the catalytic domain alone. The kcat/Km
      value of RgpA was 18-fold higher than that of RgpB and comparable to that of the
      thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA
      catalyzed protein C activation was augmented 1.4-fold by phospholipids,
      ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could
      activate protein C in plasma and this resulted in a decrease of the protein C
      concentration in plasma, which is often observed in patients with sepsis during
      the development of disseminated intravascular coagulation (DIC). These data
      indicate that RgpA is a more potent activator of protein C than RgpB and suggest
      that only the former enzyme can cause protein C activation in vivo. The present
      study further suggests that bacterial proteinases may possibly contribute to the
      consumption of plasma protein C which predisposes to DIC and/or promotes a
      thrombotic tendency towards DIC in sepsis.

PMID- 10064140
TI  - Alteration of mosaic methylation of the repeat unit of the human ribosomal RNA
      genes in lung cancer.
AB  - We have investigated the methylation status of the repeat unit of the human
      ribosomal RNA genes in lung cancer. Using a Southern blot analysis approach we
      have determined that the non-transcribed region of these genes was generally
      heavily methylated, while the transcribed region was not methylated in either
      tumor or normal DNA. Our study also revealed that, in one tumor, the boundary of
      mosaic methylation of the repeat unit was not distinct. In the same tumor, both
      the non-transcribed ribosomal spacer region and the L1 interspersed repeat
      sequences became partially demethylated. In tumor cells, the methylation status
      of DNA can be altered, but the methylation of subtelomeric repeats was found to
      be maintained. These results suggest that the mosaic methylation of the repeat
      unit is not necessarily maintained in tumor DNA, while subtelomeric repeats
      escape tumor-specific wave of demethylation.

PMID- 10064141
TI  - Degradation of the cyclic AMP antagonist prostaglandylinositol cyclic phosphate
      (cyclic PIP) by dephosphorylation.
AB  - The cAMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is
      synthesized from prostaglandin E and activated inositol phosphate. From various
      tissues only that amount of cyclic PIP can be isolated that constitutes the
      difference between synthesis and degradation. In order to overcome this drawback,
      the cyclic PIP degrading enzyme or enzymes had to be characterized prior to
      searching for inhibitors. Cyclic PIP degrading activities have been found in all
      rat tissues tested, and are lowest in brain (380 pmol x min(-1) x g(-1) wet
      weight) and highest in liver (1460 pmol x min(-1) x g(-1) wet weight). They are
      associated primarily with particulate structures of the cells, but not with the
      plasma membrane. There appear to be at least two different enzymatic activities
      involved in the degradation of cyclic PIP, because there are two pH-optima, one
      between pH 7 and 8 and another between pH 4 and 5. It is assumed that these
      activities are located in microsomes and lysosomes. Because prostaglandylinositol
      is the final product obtained in the degradation of cyclic PIP, a
      phosphodiesterase and a phosphatase should be involved, which could not yet be
      identified individually. Like alkaline phosphatase, cyclic PIP-degrading enzymes
      require Mg2+ and they are inhibited by heavy metal ions such as mercuric and
      copper chloride, by sodium fluoride and interestingly, by prostaglandins.

PMID- 10064142
TI  - Homo-dimeric spherulin 3a: a single-domain member of the beta gamma-crystallin
      superfamily.
AB  - The beta gamma-crystallin superfamily of eye lens proteins comprises a class of
      structurally related members with a wide variety of different functions. Common
      features of these proteins are 1. the Greek-key motif of antiparallel beta
      sheets, called the crystallin fold, and 2. the high intrinsic long-term
      stability. Spherulin 3a (S3a), a dormant protein from the spherules of Physarum
      polycephalum, is the only known single-domain protein within the beta gamma
      crystallin family. Based on sequence homology and 'domain swapping', it has been
      proposed to represent an evolutionary ancestor of present-day eye lens
      crystallins. Since S3a is highly expressed in spherulating plasmodia of P.
      polycephalum under a variety of stress conditions, it can be assumed that the
      protein may serve as a compatible solute in the cytosol of the slime mold. In
      order to investigate the stability and other physicochemical properties of a
      single-domain all-beta protein, we isolated natural S3a. For the large-scale
      purification, the recombinant protein was cloned and expressed in Escherichia
      coli. The detailed spectral and biochemical analysis proved the recombinant
      protein to be authentic. In its native form, S3a is dimeric. Due to its exposed
      cysteine residues (Cys4), in the absence of reducing agents intermolecular
      disulfide cross-linking leads to the formation of higher oligomers. In order to
      preserve the native quaternary structure without aggregation artifacts in
      denaturation/renaturation experiments, the Cys4-->Ser mutant (S3a C4S) was
      produced. Both the wild-type protein and its mutant are indistinguishable in
      their physicochemical properties. At pH 3 - 4, both proteins form a stable
      compact intermediate (A-state). Concentration-dependent thermal and chemical
      denaturation showed that the equilibrium unfolding of S3a obeys the simple two
      state model with no significant occurrence of folding intermediates.

PMID- 10064143
TI  - cDNA sequencing of guinea pig alpha 2-HS glycoprotein, its expression in various
      tissues and acute phase expression.
AB  - cDNA encoding alpha 2-HS glycoprotein was amplified from guinea pig liver mRNA by
      reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification
      of cDNA ends, cloned and sequenced. By RT-PCR and nested PCR, alpha 2-HS
      glycoprotein mRNA was detected not only in liver tissue but also in pancreas,
      stomach, small intestine, colon, spleen, kidney, testis, skeletal muscle, brain,
      heart and leukocytes, but not in the lung. The alpha 2-HS glycoprotein mRNA
      levels in the liver were reduced to half at 48 h after subcutaneous injection of
      turpentine oil.

PMID- 10064144
TI  - Phage display selection of P1 mutants of BPTI directed against five different
      serine proteinases.
AB  - The P1 position of protein inhibitors and oligopeptide substrates determines, to
      a large extent, association energy with many serine proteinases. To test the
      agreement of phage display selection with the existing thermodynamic data, a
      small library of all 20 P1 mutants of basic pancreatic trypsin inhibitor (BPTI)
      was created, fused to protein III, and displayed on the surface of M13 phage. The
      wild type of displayed inhibitor monovalently and strongly inhibited trypsin with
      an association constant of Ka = 3 x 10(11) M(-1). The library was applied to
      select BPTI variants active against five serine proteinases of different
      specificity (bovine trypsin and chymotrypsin, human leukocyte and porcine
      pancreatic elastases, human azurocidin). The results of enrichment with four
      proteinases agreed well with the available thermodynamic data. In the case of
      azurocidin, the phage display selection allowed determination of the P1
      specificity of this protein with the following frequencies for selected P1
      variants: 43% Lys, 36% Leu, 7% Met, 7% Thr, 7% Gln.

PMID- 10064145
TI  - Scopolamine prevents tolerance to the effects of caffeine on rotational behavior
      in 6-hydroxydopamine-denervated rats.
AB  - Continuous administration of caffeine has been shown to induce tolerance to its
      psychostimulant effects. In this study, using unilateral 6-hydroxydopamine
      nigrostriatal denervated rats, we tested the hypothesis that the muscarinic
      receptor antagonist, scopolamine, would prevent the tolerance to caffeine-induced
      contralateral rotational behavior. For that purpose we administered either
      caffeine (40 mg/kg) plus saline or scopolamine (5, 10 and 20 mg/kg) plus saline,
      as well as caffeine in combination with the various doses of scopolamine for 7
      consecutive days, and measured ipsilateral and contralateral rotational behavior.
      The results showed that acute injections of scopolamine plus saline produced
      similar levels of both ipsilateral and contralateral turning, while caffeine
      produced more contralateral than ipsilateral turning. Tolerance to caffeine
      induced contralateral turning was observed as of the second administration, while
      scopolamine plus saline injections did not produce significant changes in
      rotational behavior with repeated treatment. Scopolamine co-administered with
      caffeine significantly attenuated the increased contralateral turning produced by
      acute injections of caffeine plus saline, but significantly prevented the
      tolerance effects with repeated administration. These findings strongly suggest
      that muscarinic cholinergic processes may be involved in tolerance to caffeine
      induced contralateral turning. The results are interpreted in terms of the
      possible interactions between dopamine, adenosine and acetylcholine
      neurotransmitter systems within the basal ganglia circuitry involved in motor
      behavior.

PMID- 10064146
TI  - Tetrahydroaminoacridine and D-cycloserine fail to alleviate the water maze
      spatial navigation defect induced by hippocampal inactivation.
AB  - The present study examined the efficacy of single and combined treatment with an
      anticholinesterase, tetrahydroaminoacridine (i.p.), and a glycine-B site partial
      agonist, D-cycloserine (i.p.; a positive allosteric modulator of NMDA receptors),
      in alleviating the deficit in water maze spatial navigation induced by
      electrolytic lesion of the medial septum or lidocaine infusion into the dorsal
      hippocampi. In medial septum-lesioned rats, a combination of
      tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) facilitated
      acquisition of the water maze test more effectively than either of the drugs
      alone. Single or combined treatment with tetrahydroaminoacridine 3 mg kg(-1) and
      D-cycloserine 10 mg kg(-1) had no effect on the water maze deficit induced by
      hippocampal lidocaine infusion. These results suggest that combined treatment
      with tetrahydroaminoacridine and D-cycloserine can effectively stimulate water
      maze spatial navigation, and that functioning of the hippocampus is a
      prerequisite for this effect.

PMID- 10064147
TI  - Effects of controllable stress on masticatory behaviour and muscle structure:
      partial protective effect of clomipramine.
AB  - The influence of controllable painless stress and clomipramine treatment was
      evaluated on masticatory behaviour and myosin heavy chain expression in
      masticatory rat muscles: anterior digastric, anterior temporalis and masseter
      superficialis. The adult fast isoforms of myosin heavy chains detected were
      myosin heavy chains 2A, 2X and 2B. The myosin heavy chains composition of
      anterior temporalis muscle was unchanged by stress or by treatment. In anterior
      digastric and masseter superficialis muscles, stress induced an increase in 2B
      and a decrease in 2X and 2A. Under stress, whereas the myosin heavy chains
      composition of anterior temporalis and anterior digastric muscles was unaffected
      by clomipramine, this drug modified significantly the myosin heavy chains
      composition of masseter superficialis muscle which became comparable to that of
      control muscle. Stress-induced myosin heavy chains transformations led to an
      increased velocity of anterior digastric and masseter superficialis muscles but
      not anterior temporalis muscle. Gnawing and mastication were increased by stress
      and incisor grinding was reduced. Stress shortened the duration of gnawing and
      increased the fatigability of anterior digastric and masseter superficialis
      muscles, whereas clomipramine increased the duration of mastication and reduced
      the fatigability of masseter superficialis muscle. Stress produces selective
      changes in masticatory muscles and behaviour. This study demonstrates the muscle
      type-specific protective effect of clomipramine against stress-induced structural
      transformations of masseter superficialis muscle and the specific concomitant
      behavioural modifications.

PMID- 10064148
TI  - Dynorphin A increases substance P release from trigeminal primary afferent C
      fibers.
AB  - Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allodynia.
      Thus, we studied whether dynorphin A-(1-17) modulates substance P release evoked
      by the C-fiber-selective stimulant capsaicin (1 microM) from trigeminal nucleus
      caudalis slices. Very low concentrations of dynorphin A-(1-17) (0.01-0.1 nM)
      strongly facilitated capsaicin-evoked substance P release. This dynorphin A-(1
      17) effect was not blocked by the opioid receptor antagonists naloxone (100 nM),
      beta-funaltrexamine (20 nM), naloxonazine (1 nM), nor-binaltorphimine (3 nM) and
      ICI 174,864 (N,N-dialyl-Tyr-Aib-Phe-Leu; 0.3 microM). Yet, the effect of
      dynorphin A-(1-17) was blocked by the NMDA receptor antagonist MK-801 ((+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate; 0.3 microM).
      Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P
      containing primary afferents, abolished the excitatory effect of dynorphin A-(1
      17) on K+-evoked substance P release. In conclusion, dynorphin A-(1-17) increases
      substance P release from C-fibers by the activation of NMDA receptors which
      supports the involvement of presynaptic mechanisms in dynorphin-induced
      antianalgesia and allodynia.

PMID- 10064149
TI  - Alpha2A- but not alpha2B/C-adrenoceptors modulate noradrenaline release in rat
      locus coeruleus: voltammetric data.
AB  - In this study, we used subtype-selective antagonists to determine the subtype of
      alpha2-adrenoceptor controlling noradrenaline release in rat locus coeruleus.
      Noradrenaline release was measured in locus coeruleus slices using fast cyclic
      voltammetry at carbon fibre microelectrodes. On long stimulation trains (40
      pulses, 20 Hz), the alpha2A-adrenoceptor selective antagonist BRL 44408 (2-[2H-(1
      methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole) at 100 nM and 1 microM
      significantly increased stimulated noradrenaline release, whereas the alpha2B/C
      selective antagonist ARC 239 (2-[2[4-(o-methoxyphenyl)piperazin-1-yl] ethyl]
      4,4dimethyl-1,3-(2H,4H)-isoquinolinedione) at 50 and 500 nM had no effect. On
      short stimuli (20 pulses, 200 Hz), the non-specific alpha2-adrenoceptor agonist
      dexmedetomidine (10 nM) significantly decreased noradrenaline release, an effect
      reversed by BRL 44408 (1 microM) but not by ARC 239 (500 nM). These data
      demonstrate that autoreceptor control of noradrenaline release in the locus
      coeruleus is mediated by alpha2A but not alpha2B/C-adrenoceptors.

PMID- 10064150
TI  - Endogenous noradrenergic tone controls symptoms of allodynia in the spinal nerve
      ligation model of neuropathic pain.
AB  - Endogenous inhibitory controls were studied in the spinal nerve ligation model of
      neuropathic pain. Atipamezole, a selective alpha2-adrenoceptor antagonist,
      produced both mechanical and cold allodynia in those rats which had not developed
      clear neuropathic symptoms. The same doses (50 microg i.t. or 1 mg/kg s.c.) did
      not increase the severity of symptoms in rats which had developed them. The
      opioid receptor antagonist naloxone (20 microg i.t. or 1 mg/kg s.c.) had no
      effect on the neuropathic symptoms. These results indicate that mechanical and
      cold allodynia are under endogenous noradrenergic rather than opioidergic control
      in this model of neuropathic pain.

PMID- 10064151
TI  - Effects of corticosteroid, contrast medium and ATP on focal microcirculatory
      disorders of the cochlea.
AB  - We evaluated the ability of various drugs to prevent the decrease in focal
      cochlear blood flow induced by photochemical reaction and investigated the
      mechanisms underlying this decrease. By means of a photochemical reaction, which
      produces reactive oxygen species, focal lesions measuring about 1 mm in diameter
      were induced in the lateral wall of the guinea pig cochlea. The protective
      effects of hydrocortisone, amidotrizoate and ATP on cochlear blood flow and
      cochlear vascular conductance changes were evaluated by using a non-contact laser
      flowmeter. Cochlear blood flow and cochlear vascular conductance were decreased
      to 65.1+/-4.9% (mean +/- S.E.M.) and 57.0+/-3.7% (mean +/- S.E.M.) of the initial
      level 30 min after the start of the photochemical reaction, respectively.
      Hydrocortisone significantly prevented the decline in the cochlear blood flow and
      cochlear vascular conductance and reduced the area of stria vascularis
      degeneration in a dose-dependent manner. Neither amidotrizoate nor ATP
      significantly prevented the decrease in cochlear blood flow or cochlear vascular
      conductance. Hydrocortisone was more effective than vasodilators or other agents
      which increase cochlear blood flow in preventing the photochemically induced
      decrease in cochlear blood flow. This might be due to the antioxidative effects
      of hydrocortisone.

PMID- 10064152
TI  - Effects of chronic ethanol consumption on aortic constriction in male and female
      rats.
AB  - This study was designed to determine if gender influences the effects of chronic
      ethanol intake on vasoconstrictive responsiveness. Ethanol-preferring rats were
      allowed ad libitum access to tap water or tap water containing 20% or 30% ethanol
      for 16 weeks. All of the ethanol groups consumed more daily calories than their
      respective controls, and female rats consumed more ethanol calories per unit body
      mass than their male counterparts. Following treatment, endothelium-intact and
      endothelium-denuded thoracic aortic rings were used to examine the contractile
      response to phenylephrine. Ethanol consumption did not alter vasoconstriction in
      endothelium-intact aortae from either gender. In contrast, males, but not
      females, demonstrated an ethanol-associated increase in the maximum response to
      phenylephrine in endothelium-denuded preparations. Aortae from male rats that
      consumed 20% and 30% ethanol showed an increased contractility of 37% and 85%,
      respectively. These data indicate that gender influences the vasoconstrictive
      effects elicited by chronic ethanol consumption and suggest that males may be
      more susceptible to the associated hypertension.

PMID- 10064153
TI  - Ca2+ buffering action of sarcoplasmic reticulum on Bay k 8644-induced Ca2+ influx
      in rat femoral arterial smooth muscle.
AB  - We examined the Ca2+ buffering action of sarcoplasmic reticulum during the
      stimulation of arterial smooth muscle with Bay k 8644 [methyl-1,4-dihydro-2,6
      dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyr idine-5-carboxylate]. The
      effects of Bay k 8644 on tension and cellular Ca2+ level were first determined in
      endothelium-denuded strips of rat femoral artery. The Ca2+ buffering action was
      examined by using cyclopiazonic acid and thapsigargin to inhibit Ca2+-ATPase of
      sarcoplasmic reticulum and ryanodine to deplete Ca2+ stored in sarcoplasmic
      reticulum. The addition of Bay k 8644 (0.3-300 nM) to the resting strips almost
      failed to cause a contraction. When the strips were preincubated with 10 microM
      cyclopiazonic acid, Bay k 8644 induced a concentration-dependent contraction that
      is antagonized by nifedipine. The maximum contraction induced by Bay k 8644 in
      the presence of cyclopiazonic acid was comparable to the maximum contraction
      induced by 65.9 mM K+-depolarization and the ED50 value for Bay k 8644 was around
      5 nM. Similar results were obtained when the strips were preincubated with 30 nM
      thapsigargin or 10 microM ryanodine. Bay k 8644 also induced a strong contraction
      when the extracellular K+ concentration was elevated. During the stimulation with
      100 nM Bay k 8644, the Ca2+ influx was increased. We conclude that in rat femoral
      arterial smooth muscle, (1) the Ca2+ influx induced by Bay k 8644 is completely
      buffered by Ca2+ uptake into the sarcoplasmic reticulum, and (2) this
      sarcoplasmic reticulum can buffer a large amount of Ca2+ that induces a maximum
      contraction.

PMID- 10064154
TI  - Pharmacological characterization of histamine H3 receptors in human saphenous
      vein and guinea pig ileum.
AB  - Studies were performed to assess the functional activity of histamine H3
      receptors on neurogenic sympathetic end organ responses in cryopreserved human
      saphenous vein. (R)-alpha-methylhistamine inhibited electrical field stimulation
      evoked contractile responses in a dose dependent manner (pD2 = 8.20). Prazosin (1
      microM) and tetrodotoxin (1 microM) blocked the electrical field stimulation
      evoked contractile responses in human saphenous vein indicating a sympathetic
      neural origin of these contractions. The histamine H3 antagonists thioperamide
      (pA2 = 8.41) and clobenpropit (pA2 = 10.10) produced parallel rightward shifts in
      the concentration response curve to (R)-alpha-methylhistamine in human saphenous
      vein and guinea pig ileum (pA2 = 8.59 and 9.83, respectively). Pretreatment with
      (R)-alpha-methylhistamine (1 microM) did not alter contractions to exogenous
      norepinephrine in human saphenous vein. In addition, clonidine (pD2 = 10.28)
      inhibited electrical field stimulation-evoked contractile responses in human
      saphenous vein which were blocked by yohimbine (30 nM, pA2 = 9.92) but did not
      alter the (R)-alpha-methylhistamine dose response curve. These results
      demonstrate the presence of functional presynaptic histamine H3 heteroreceptors
      on cryopreserved human saphenous vein sympathetic nerves that, upon activation,
      attenuate electrical field stimulation-evoked contractile responses in this
      vessel.

PMID- 10064155
TI  - Dual actions of S-nitrosylated derivative of vasoactive intestinal peptide as a
      vasoactive intestinal peptide-like mediator and a nitric oxide carrier.
AB  - Vasoactive intestinal peptide (VIP) has been postulated as a non-adrenergic non
      cholinergic (NANC) transmitter in the relaxation of vascular and non-vascular
      systems. In order to synergize the vasoactivities of VIP with nitric oxide (NO),
      we synthesized a S-nitrosylated derivative of VIP, VIP-Gly-Cys-NO (VIPGC-NO). On
      aortic rings, VIPGC-NO exhibited a dose-dependent vasorelaxation similar to S
      nitrosoglutathione (GSNO), and both induced complete vasorelaxation at 1 microM,
      whereas, VIP at 1 microM only produced 19% relaxation. The degree of
      vasorelaxation was proportional to the increases in cyclic GMP with no
      significant enhancement in cyclic AMP (cAMP) level. On precontracted tracheal
      rings, VIP, VIPGC-NO, VIPGC and GSNO produced relaxation with EC50 of 74+/-5,
      32+/-6, 59+/-9, and 251+/-32 nM, respectively, which was consistent with
      increases in cyclic GMP (cGMP). A marked increase in cAMP was observed from the
      tracheal rings pretreated with VIP, VIPGC-NO and its parent VIP-Gly-Cys (VIPGC)
      as well as isoproterenol. Propranolol only blocked the airway relaxation induced
      by isoproterenol, but did not antagonize the relaxation induced by VIP, VIPGC and
      VIPGC-NO. On rabbit sphincter of Oddi, VIP, VIPGC-NO and VIPGC inhibited both
      basic and acetylcholine-induced contraction frequency and amplitude, whereas,
      GSNO was less potent than VIP and its derivatives over a range of 2 log units in
      this respect. On rat gastric fundus, these compounds inhibited contraction
      amplitude and frequency induced with 5-hydroxytryptamine (5-HT) in the order of
      inhibitory potency VIP > VIPGC-NO > VIPGC > isoproterenol > GSNO. Our data
      suggest that: (1) NO is selective in relaxing vascular smooth muscle via the cGMP
      pathway, whereas VIP is selective in relaxing non-vascular smooth muscles via the
      activation of both cGMP and cAMP pathways; (2) VIPGC-NO preserves the intrinsic
      function of VIP but acquires NO-like vasoactivities.

PMID- 10064156
TI  - Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat.
AB  - The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats
      were compared with those in young rats. The incorporation of [3H]glucosamine and
      [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa
      from 7-week-old rats. In contrast, tetragastrin could not enhance mucin
      biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced
      stimulation of corpus mucin biosynthesis observed in middle-aged rats was
      essentially the same as that seen in young rats. Nitric oxide (NO) synthase
      activity of the corpus was significantly reduced in the middle-aged rats compared
      to the young rats. NO synthase-immunoreactivity was observed at surface mucous
      cells in the corpus mucosa of young, but not of middle-aged, rats. These results
      suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis
      through the age-related loss of NO synthase function in the surface mucous cell
      layer of rat stomach.

PMID- 10064157
TI  - Evidence for a G protein-coupled diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)
      receptor binding site in lung membranes from rat.
AB  - Nucleotide receptors are of considerable importance in the treatment of lung
      diseases, such as cystic fibrosis. Because diadenosine polyphosphates may also be
      of significance as signalling molecules in lung, as they are in a variety of
      tissues, in the present work we investigated the binding sites for
      [3H]diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) in plasma membranes from rat
      lung and studied their possible coupling to G proteins. We present evidence for a
      single high-affinity binding site for [3H]Ap4A with similar affinity for other
      diadenosine polyphosphates ApnA (n = 2 to 6). Displacement studies with different
      nucleotides revealed that the [3H]Ap4A binding site was different from P2X and
      P2Y2 receptor binding sites. Pretreatment of lung membranes with GTPgammaS or GTP
      in the presence of Mg2+ increased the Ki for Ap4A from 91 nM to 5.1 microM, which
      is indicative of G protein coupling. The putative coupling to G proteins was
      further confirmed by the enhancement of [35S]GTPgammaS binding (to Galpha
      proteins) to lung membranes by Ap4A (63% increase over basal) in a concentration
      dependent manner. Therefore, our data for the first time provide evidence of a G
      protein-coupled Ap4A binding site in lung membranes.

PMID- 10064158
TI  - LY-83583 stimulates glucose transporter-1-mediated glucose transport independent
      of changes in cGMP levels.
AB  - Exposure of Clone 9 cells, a nontransformed rat liver cell line expressing only
      the Glutl glucose transporter isoform, to the guanylyl cyclase inhibitor LY-83583
      was found to stimulate the rate of glucose transport (approximately 7- to 8-fold
      in 1 h). A similar response to LY-83583 was found in NIH 3T3 fibroblasts, 3T3-L1
      pre-adipocytes, and C2C12 myoblasts. Neither the rate of glucose transport in
      cells under control conditions nor the effect of LY-83583 on glucose transport
      was altered by 10, 50, or 100 microM 8-bromo-cGMP or by addition of cGMP
      phosphodiesterase inhibitors, zaprinast, or dipyridamole suggesting that glucose
      transport and the response to LY-83583 is independent of cGMP levels. In
      addition, the effect of LY-83583 on glucose transport was not mediated by
      inhibition of oxidative phosphorylation, since exposure to the agent resulted in
      no increase in lactate production. Incubation of Clone 9 cells in the presence of
      the phospholipase C inhibitor U73122, however, attenuated the glucose transport
      response to LY-83583. Moreover, exposure to LY-83583 resulted in a rise in cell
      diacylglycerol content, and preincubation with U73122 significantly diminished
      this rise as well as the glucose transport response to LY-83583. The stimulatory
      effect of LY-83583 on glucose transport was significantly blocked by
      thapsigargin. Down-regulation of protein kinase C activity, resulting from 24 h
      pre-incubation in the presence of 160 nM phorbol-12-myristate 13-acetate, did not
      attenuate the glucose transport response to LY-83583. It is concluded that the
      stimulation of glucose transport in response to LY-83583 is independent of
      changes in cGMP levels, is not mediated by inhibition of oxidative
      phosphorylation, and is mediated, at least in part, through stimulation of the
      phospholipase C pathway.

PMID- 10064159
TI  - Role of nitric oxide production in carbachol-induced negative chronotropy in
      cultured rat ventricular myocytes.
AB  - It has been reported that nitric oxide (NO) plays a physiological role in
      mediating the effect of vagal stimulation in the autonomic regulation of the
      heart. In this study, the changes in NO production induced by carbachol were
      investigated by measuring the NO metabolites, nitrite (NO2-) and nitrate (NO3-),
      with a high-performance liquid chromatography-Griess reaction system, and the
      carbachol-induced chronotropic response was simultaneously investigated. Cultured
      rat ventricular myocytes exhibited a dose-dependent negative chronotropic
      response and NO metabolite production in response to carbachol. The negative
      chronotropy and the enhancement of NO metabolite production induced by 10(-4) M
      carbachol were completely abolished by 10(-6) M atropine. Both of these effects
      of carbachol were completely abolished by NO synthase inhibitors such as 3 X 10(
      4) M NG-monomethyl-L-arginine acetate and 10(-5) M methylene blue. Furthermore,
      the negative chronotropic effect induced by 10(-4) M carbachol was also abolished
      by 10(-6) M 1 H-[1,2,4]oxadiazolo[4,3-alpha]quanoxalin-1-one, a selective
      guanylyl cyclase inhibitor. In addition, 10(-4) M 8-bromoguanosine 3':5'-cyclic
      monophosphate, a cell-permeable analogue of guanosine 3':5'-cyclic monophosphate,
      caused a negative chronotropic effect. These results suggest that the NO
      signaling pathway may play an important role in the muscarinic cholinergic
      regulation of myocardial function.

PMID- 10064160
TI  - Binding and functional characterization of alpha1-adrenoceptor subtypes in the
      rat prostate.
AB  - The alpha1-adrenoceptor subtypes of rat prostate were characterized in binding
      and functional experiments. In binding experiments, [3H]tamsulosin bound to a
      single class of binding sites with an affinity (pKD) of 10.79+/-0.04 and Bmax of
      87+/-2 fmol mg(-1) protein. This binding was inhibited by prazosin, 2-(2,6
      dimethoxy-phenoxyethyl)-aminomethyl-1,4-benzodioxane hydrochloride (WB4101), 5
      methylurapidil, alpha-ethyl-3,4,5,-trimethoxy-alpha-(3-((2-(2
      methoxyphenoxy)ethyl)-amin o)-propyl)benzeneacetonitrile fumarate (HV723) and
      oxymetazoline with high efficacy, resulting in a good correlation with the
      binding characteristics of cloned alpha1a but not alpha1b and alpha1d
      adrenoceptor subtypes. In functional studies, noradrenaline and oxymetazoline
      produced concentration-dependent contractions. These contractions were
      antagonized by tamsulosin, prazosin, WB4101 and 5-methylurapidil with an efficacy
      lower than that exhibited by these agents for inhibition of [3H]tamsulosin
      binding. The relationship between receptor occupancy and contractile amplitude
      revealed the presence of receptor reserve for noradrenaline, but the contraction
      induced by oxymetazoline was not in parallel with receptor occupation and
      developed after predicted receptor saturation. From these results, it is
      suggested that alpha1A-adrenoceptors are the dominant subtype in the rat prostate
      which can be detected with [3H]tamsulosin, but that the functional subtype
      mediating adrenergic contractions has the characteristics of the alpha1L
      adrenoceptor subtype, having a lower affinity for prazosin and some other drugs
      than the alpha1A-adrenoceptor subtype.

PMID- 10064161
TI  - From stroke unit care to stroke care unit.
AB  - In some stroke units continuous monitoring of blood pressure, electrocardiogram,
      body temperature, and oxygen saturation has become an integral part of the
      management of acute stroke. In addition, regular measurements of blood glucose
      are performed. Stroke units equipped with such monitoring facilities should be
      named 'stroke care units' by analogy with coronary care units. The goal of a
      stroke care unit is early detection and rapid correction of extracranial factors
      which may aggravate cerebral damage in ischemic brain, including hypoxia,
      hyperglycemia, hypotension, cardiac arrhythmias, and elevated body temperature.

PMID- 10064162
TI  - Enlargement of cortical vibrissa representation in the surround of an ischemic
      cortical lesion.
AB  - It has been shown that cortical lesions are associated with an increase of
      excitability in surrounding brain regions, and with a downregulation of GABA(A)
      receptors. In the present study we investigated whether this increased
      excitability affects the cortical map of inputs represented in areas surrounding
      the lesioned brain area. Focal lesions with a diameter of 2-2.5 mm were induced
      photochemically in the hindlimb area at the border of the primary somatosensory
      cortex of the rat. One week after lesioning, the cortical representation of the
      B3 vibrissa was studied using 14C-deoxyglucose (DG) autoradiography. In all
      animals mechanical stimulation of the B3 vibrissa produced a column-shaped DG
      labeling in the somatosensory cortex, corresponding to the B3-barrel with a
      maximum of the glucose uptake in layer IV. In control animals without cortical
      lesions (n=6), stimulation increased the glucose uptake rate by 50.8+/-10.5% in
      layer IV. In lesioned animals (n=6) maximum DG-uptake in layer IV (54.8+/-8.6%)
      did not differ significantly from that in controls. However, as compared to
      control animals, lesioned animals showed also increased glucose uptake within the
      activated column in layers II/II (51.+/-11.1%, lesioned animals; 31.8+/-11.2%,
      controls; P<0.05, lesioned vs. control) and V (47.5+/-5.8%, lesioned animals,
      28.8+/-10.5%, controls; P<0.05, lesioned vs. control). The diameter of the
      metabolically activated B3-barrel area of layer IV was expanded from 461.8+/-77.6
      microm in control animals to 785.5+/-103.6 microm; P<0.01) in lesioned animals.
      Lesioned animals also showed expansion of the activated area in layers II/III
      (890.4+/-134.8 microm, lesioned animals; 430.6+/-95.1 microm, controls; P<0.01)
      and layer V (1117.5+/-163.6 microm, lesioned animals; 648.7+/-114.1 microm,
      controls; P<0.01). The depth profile of the activation columns showed a maximum
      in layer IV in control animals, which was expanded towards layers II/III and
      layer V in lesioned animals. It is concluded that cortical lesions alter the
      representational area of neighboring afferent inputs through disinhibition or
      'unmasking' of pre-existing silent or ineffectual intracortical synapses. The
      present observations raise the possibility that the brain supports recovery from
      lesions by decreasing GABAergic inhibition, thereby facilitating a remapping of
      the cortical representation in neighboring brain areas.

PMID- 10064163
TI  - EEG burst suppression is not necessary for maximum barbiturate protection in
      transient focal cerebral ischemia in the rat.
AB  - Barbiturates have been demonstrated to reduce the cerebral metabolic rate (CMR)
      in a dose-dependent manner but investigations of a dose-response relationship for
      their neuroprotective efficacy are scant. It has been suggested that barbiturates
      possess other mechanism of action that may be critical to their protective
      effect. If so, it is conceivable that the peak effect of such mechanisms does not
      parallel the reduction in CMR. Thus, maximal neuroprotection may be achieved with
      a substantially lower dose of the drug. Thirty Sprague-Dawley rats were subjected
      to 2 h of middle cerebral artery occlusion while either anesthetized with (1)
      halothane (control) or (2) intravenous thiopental titrated to cause mild EEG
      suppression or (3) thiopental titrated to maintain EEG burst suppression.
      Cortical blood flow was recorded by continuous bilateral laser Doppler flowmetry
      (LDF). Infarct volume was assessed after 3 h of reperfusion. Low-dose thiopental
      decreased blood flow to 80% of baseline and high-dose thiopental to 70% of
      baseline. LDF did not indicate improvement of blood flow by thiopental in the
      ischemic area. Compared to controls, low-dose thiopental significantly decreased
      infarct volume by 28% and high-dose thiopental by 29%. The results of this study
      and a review of literature indicate that barbiturates provide cerebral protection
      but that the magnitude of this effect has been overestimated. Other mechanisms
      than CMR reduction seem to contribute to their beneficial effects, and high doses
      administered to the point of burst suppression may not be required to obtain
      maximal protection.

PMID- 10064164
TI  - Meningitis in a community with a high prevalence of tuberculosis and HIV
      infection.
AB  - OBJECTIVES: To evaluate the spectrum of aetiologies, and distinguishing clinical
      and laboratory features, of meningeal infection in a community with a high
      prevalence of tuberculosis (TB) and HIV infection. SETTING: A hospital serving
      mineworkers, originating from rural areas of Southern Africa. DESIGN: Prospective
      cohort of 60 consecutive lumbar punctures (LPs), performed for suspected
      meningitis. MEASUREMENTS: Clinical history and examination; concurrent
      cerebrospinal fluid (CSF) and blood samples; mortality status six months after
      entry to study. RESULTS: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of
      whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis
      (TBM) and two had tuberculomas; four developed disease while on TB therapy. There
      was one case of multidrug, and two of isoniazid-resistant TBM. There were nine
      episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis,
      two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex
      (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were
      significantly younger (p=0.004). All patients with tuberculous, cryptococcal
      (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive.
      Within six months, 19 patients had died. Death was associated with HIV positivity
      (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis,
      CNS TB or ADC. CONCLUSION: HIV has a major impact on the burden of disease and
      mortality, with a predominance of opportunistic chronic meningitides, despite a
      meningococcal outbreak, in this community. Of concern is the development of TBM
      despite therapy, and the emergence of drug-resistant strains.

PMID- 10064165
TI  - Slowed cognitive processing and high workload in Parkinson's disease.
AB  - It is suggested that cognitive slowing in Parkinson's disease (PD) may be evident
      on a task with high cognitive load. This hypothesis was tested using a workload
      design with a progressive increase in task difficulty, on a group of Parkinson
      patients and normal controls. Using measures of Reaction Time (RT) and Event
      Related Potentials (ERP), results showed that RT and ERP waveforms increased in
      line with task difficulty. The RT data was not significantly different between
      groups but the ERP showed a much reduced P300 in the patient group. These results
      are indicative of cognitive slowing in PD, at the stage of stimulus evaluation
      but not for response selection. An interpretation of the literature in terms of
      reduced activation in relation to cognitive slowing is discussed.

PMID- 10064166
TI  - Cu/Zn superoxide dismutase activity at different ages in sporadic amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive disorder resulting from
      degeneration of motor neurons in the brain and spinal cord. Sporadic ALS (SALS)
      accounts for the majority of patients and the familial form (FALS) represents
      fewer than 10% of all cases. Since it was found that there are Cu/Zn superoxide
      dismutase (SODI) gene mutations in 20% of FALS patients and that FALS and SALS
      patients show similar clinical features, it has been postulated that both may
      share a common physiopathological mechanism. We studied Cu/Zn SOD1 activity in
      cytosolic extracts of erythrocytes from 125 normal individuals and 40 SALS
      patients. We found that enzyme activity does not change with age in control
      subjects and tends to decrease in most SALS patients older than 60 years. A
      subpopulation of five SALS patients had significantly increased SOD1 activity;
      four of these patients over 70 years old. There was no correlation between enzyme
      activity and time of onset of the disease, or clinical forms of the illness. The
      variation in SOD1 activity in ageing SALS patients compared with younger patients
      suggests that they may undergo an oxidative disbalance contributing to the
      development of the disease.

PMID- 10064167
TI  - Decreased expression of myotonic dystrophy protein kinase and disorganization of
      sarcoplasmic reticulum in skeletal muscle of myotonic dystrophy.
AB  - Pathological expression of myotonic'dystrophy protein kinase (DMPK) in skeletal
      muscle of myotonic dystrophy (DM) was studied by Western blot analysis,
      immunohistochemistry, and immunoelectron microscopy of DMPK. Western blot
      analysis showed that DMPK protein in DM skeletal muscles dramatically decreased.
      DMPK-positive muscle fibers showed typical DM pathological changes such as type I
      atrophy, central nuclei, nuclear chains, and sarcoplasmic masses. In degenerated
      DMPK-positive muscle fibers, cross-striated bands disappeared, and irregular
      granular DMPK-positive materials appeared in sarcoplasm. By immunoelectron
      microscopy, DMPK was localized in the terminal cisternae of the sarcoplasmic
      reticulum (SR) in DM muscle. Swollen DMPK-positive SRs were detected between well
      preserved myofibrils in the early stage of DM muscle degeneration, and
      degenerated intramembranous structures with DMPK and an accumulation of
      mitochondria were observed between disorganized myofibrils in degenerated DM
      muscle. We concluded that SR is the primary site of the degeneration of DM
      skeletal muscle and that the decreased DMPK might cause dysregulation of
      intracellular calcium metabolism, which is followed by DM muscle degeneration.

PMID- 10064168
TI  - Corpus callosum atrophy and cerebral blood flow in chronic alcoholics.
AB  - The corpus callosum atrophy and cerebral blood flows were investigated in chronic
      alcoholics without Marchiafava-Bignami disease. Fifteen cases of chronic
      alcoholics and 15 age-matched healthy controls were studied. The sagittal plane
      of magnetic resonance imaging of the head was scanned into a computer and the
      corpus callosum was measured and the callosal index was calculated. Cerebral
      blood flows were measured using stable xenon computed tomography (CT) method.
      Regional cerebral blood flows in the frontal, temporal, parietal and occipital
      cortex, frontal, temporal and occipital white matter, caudate nucleus, putamen
      and thalamus were measured. The corpus callosum area, the thickness of the genu,
      the thickness of the trunk, the thickness of the splenium, and the callosal index
      were significantly smaller in the chronic alcoholic group than in the healthy
      control group. Blood flows in the cerebral cortex, thalamus and putamen were
      significantly lower in the chronic alcoholic group than in the healthy control
      group. Significant positive correlations were present between the corpus callosum
      atrophy and the cerebral cortex blood flows. Corpus callosum atrophy and
      decreased cerebral blood flows may be seen in chronic alcoholics without
      Marchiafava-Bignami disease.

PMID- 10064169
TI  - Clinical, immunological and MRI features of myelitis with atopic dermatitis
      (atopic myelitis).
AB  - In order to clarify the characteristic features of myelitis with atopic
      dermatitis (AD), we compared the clinical, immunological and MRI findings between
      14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic
      patients with AD showed the following distinct features, compared with those
      without AD. (1) A preferential involvement of the cervical cord, as shown by
      neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2)
      paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of
      definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12;
      P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5;
      P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the
      IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms
      and MRI lesions during the follow-up periods (mean, 17 months). In addition, both
      the serum total IgE level and the frequency of specific IgE to Dermatophagoides
      farinae were significantly higher in the myelitic patients with AD (median
      IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034
      and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001
      and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features
      and atopy to mite antigens appears to be the underlying cause of this condition,
      it may therefore be a distinct subtype of myelitis.

PMID- 10064170
TI  - Alpha-interferon and isoprinosine in adult-onset subacute sclerosing
      panencephalitis.
AB  - We report eight patients with adult-onset subacute sclerosing panencephalitis
      (SSPE), of which, four were treated with oral isoprinosine and four with
      intraventricular alpha-interferon plus oral isoprinosine. One of the four
      patients treated with oral isoprinosine died within two months, and the disease
      progressed in three patients. Of the four patients treated with oral isoprinosine
      plus intraventricular alpha-interferon, one showed mild progression, one
      remission, and the remaining two showed stabilization. The group of patients is
      relatively small, but our results suggest that treatment with oral isoprinosine
      plus alpha-interferon is effective for SSPE.

PMID- 10064171
TI  - Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy,
      lactic acidosis, and stroke-like episodes (MELAS): evaluation by noninvasive
      tissue oximetry.
AB  - We evaluated the effect of coenzyme Q10 supplementation to two patients with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS) by using noninvasive tissue oximetry with near-infrared spectra of
      hemoglobin from the quadriceps muscle during bicycle ergometer exercise. Patients
      showed distinct oxygen consumption patterns reflecting the defect in oxidative
      phosphorylation and the impairment in oxygen utilization during exercise. Based
      on the oxygen consumption pattern, we considered one patient as having severe
      mitochondrial disorder and another patient as having mild one. After coenzyme Q10
      supplementation, the oxygen consumption pattern of the patient with the severe
      form shifted to the mild one, while that of the patient with mild form remained
      unchanged. The shift of the pattern to the mild form correlated well with
      reduction of the sum of the serum lactate and pyruvate content during exercise.
      Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10
      supplementation to patients with mitochondrial encephalomyopathy including MELAS.

PMID- 10064172
TI  - The effect of dehydroepiandrosterone sulfate administration to patients with
      multi-infarct dementia.
AB  - We measured cerebrospinal fluid (CSF) levels of dehydroepiandrosterone sulfate
      (DHEAS) by radioimmunoassay in seven patients with multi-infarct dementia (MID),
      fourteen age- and gender-matched non-demented patients with a history of cerebral
      infarction and fifteen age- and gender-matched patients without neurological
      disorders. The levels of DHEAS in CSF of patients with MID were significantly
      lower than those in non-demented patients with a history of cerebral infarction
      or those in patients without neurological disorders. Daily intravenous
      administration of 200 mg DHEAS for 4 weeks markedly increased serum and CSF
      levels of DHEAS in seven MID patients, improved decrease of daily activities and
      emotional disturbances in three patients and EEG abnormalities in two patients.
      The DHEAS therapy may provide a beneficial effect on MID patients.

PMID- 10064173
TI  - Autoimmune events during interferon beta-1b treatment for multiple sclerosis.
AB  - Autoimmune events, although rarely reported during interferon beta-1b (IFNB)
      treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more
      frequent than expected due to the many immunologic abnormalities associated with
      this disease. We report the prospective two-year follow-up of autoimmune events
      in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid
      and liver function and serum level of 12 autoantibodies (autoAbs) against organ-
      (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially
      monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle
      or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were
      associated with thyroid or liver function alteration in many cases. Persistent
      autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of
      whom were women with a familial history of thyroid disease or baseline anti
      thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid
      dysfunction was adequately treated without stopping IFNB. Liver function
      alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs
      in four) was transient and did not require IFNB treatment to be stopped, with the
      exception of one patient who was already suffering from a drug-induced
      hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune
      events may occur, indicating that thyroid and liver function and autoAbs must be
      carefully monitored.

PMID- 10064174
TI  - Endoneurial microvascular abnormalities of sural nerve in non-diabetic chronic
      atherosclerotic occlusive disease.
AB  - Neuropathic abnormalities are found in chronically ischaemic limbs associated
      with non-diabetic atherosclerotic peripheral vascular disease (PVD). In chronic
      ischaemic neuropathy, microvascular alterations play a key role in its
      development. We undertook morphometric assessment of endoneurial microvessels in
      the sural nerves, taken from severely ischaemic amputated legs in nine chronic
      non-diabetic PVD. These subjects had threatened ischaemic limbs and revealed
      clinical, physiological and pathological evidence of neuropathy. For comparison,
      sural nerves taken from amputated legs due to non-ischaemic disorders (n=4) and
      chronic PVD associated with diabetes (n=3) were also assessed. We evaluated the
      areas of vascular lumen, endothelial cells and whole vessel, as well as the
      percentage of closed capillaries. Endothelial area of sural nerve microvessels in
      non-diabetic PVD nerves was significantly greater than in non-ischaemic control
      nerves. Periendothelial cell area containing pericytes and basement membranes was
      also significantly increased in non-diabetic PVD nerves when compared with
      control nerves. Vascular lumen area was significantly less in non-diabetic PVD
      nerves than in non-ischaemic control nerves. Endoneurial microvessels in diabetic
      PVD nerves showed similar results: thickened vessel wall and smaller lumen.
      Periendothelial area in diabetic nerves was significantly greater than in non
      diabetic PVD nerves. We demonstrated swollen endothelial cells and increased
      periendothelial area associated with narrowed lumen in sural nerve endoneurial
      microvessels of severe chronic PVD. Basement membrane reduplication of
      endoneurial capillaries was seen in non-diabetic PVD nerves. These microvascular
      abnormalities could play an important role in the development of chronic
      ischaemic neuropathy in PVD limbs.

PMID- 10064175
TI  - A woman with a sudden tinnitus and back pain.

PMID- 10064176
TI  - Subacute painful lumbosacral polyradiculoneuropathy in immunocompromised
      patients.
AB  - The syndrome of inflammatory subacute lumbosacral polyradiculoneuropathy (SLP)
      has been reported in acquired immunodeficiency syndrome (AIDS) patients in
      association with cytomegalovirus infection and is only partially amenable to anti
      viral therapy. We report three cases of relatively benign inflammatory painful
      SLP in two non-AIDS, immunosuppressed patients and one who HIV-seroconversed at
      the time of clinical presentation. SLP developed: (1) in association with HIV
      seroconversion; (2) during ECHO virus infection in a patient with common variable
      immune deficiency; and (3) after a severe systemic infection that induced
      transient immunosuppression due to Epstein-Barr virus reactivation. This report
      expands the spectrum of viruses associated with acute and subacute lumbosacral
      polyradiculoneuropathy and may shed light on its possible pathogenesis.

PMID- 10064177
TI  - Seizures induced by frustration and despair due to unresolved moral and political
      issues: a rare case of reflex epilepsy.
AB  - We present a case of reflex-induced simple partial seizures, triggered by
      feelings of frustration, anger and despair. Such emotions were provoked by
      pondering over complex national and international, political and moral issues.
      The present case may suggest that activation of right temporal networks may
      mediate negative and adverse emotions induced by preoccupation with agitating,
      controversial issues.

PMID- 10064178
TI  - Vitamin E deficiency ataxia associated with adenoma.
AB  - Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe
      vitamin E deficiency (VED) can have a profound effect on the central nervous
      system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's
      ataxia. We report here a patient presenting this syndrome, but also a prolactin
      and FSH adenoma. Both the neurological syndromes and the adenoma regressed after
      treatment with alpha-tocopherol. Although, the presence of the prolactinoma in
      this patient may not be related to his vitamin E deficiency, alpha-tocopherol
      treatment seems to be beneficial and might usefully be tested in patients with
      hypophyseal secreting other forms of adenoma.

PMID- 10064179
TI  - Manganese intoxication during total parenteral nutrition: report of two cases and
      review of the literature.
AB  - We report two cases of manganese (Mn) intoxication during total parenteral
      nutrition including manganese (Mn). Both patients showed parkinsonism with
      psychiatric symptoms and elevated serum Mn levels. T1-weighted magnetic resonance
      images (MRI) revealed symmetrical high intensity lesions in the globus pallidus.
      Discontinuation of Mn supplementation and levodopa treatment improved the
      symptoms and MRI abnormalities in the both patients. Thus, careful attention
      should be paid to the long-term intravenous administration of Mn.

PMID- 10064180
TI  - Micrographia in Huntington's disease.

PMID- 10064181
TI  - Neuroleptic malignant syndrome associated with diphenhydramine and diprophyllin
      overdose in a depressed patient.

PMID- 10064182
TI  - Late effects of chemotherapy compared to bone marrow transplantation in the
      treatment of pediatric acute myeloid leukemia and myelodysplasia.
AB  - BACKGROUND: As more pediatric patients with acute myeloid leukemia (AML) and
      myelodysplastic syndrome (MDS) survive, comparison of the late effects of various
      therapies becomes increasingly important. This study of survivors of AML is the
      largest to date comparing the late effects of patients treated with chemotherapy
      (CT) with or without irradiation (RT) or CT followed by bone marrow
      transplantation (BMT). PROCEDURE: In a retrospective review of 228 patients with
      AML or MDS from 1970 to 1995, 62 survived and had follow-up data available more
      than 1 year following completion of therapy. Ten patients with Down syndrome were
      excluded. Twenty-six received CT and 26 underwent BMT. Weight and height Z
      scores, endocrine, ophthalmologic, renal, and cardiac function following CT +/-
      RT or BMT +/- total body irradiation (TBI) were compared at a mean follow-up of
      7.4 and 5.6 years, respectively. RESULTS: Both groups experienced a decrement in
      height and increase in weight. The mean height Z score in the CT group fell from 
      0.29 to -0.72 (P = 0.02) and mean weight Z score rose from -0.06 at diagnosis
      (T0) to 0.51 at last follow-up (T2) (P = 0.02), a finding no longer significant
      when patients who received RT were excluded. The mean height Z score in the BMT
      group fell from -0.17 at TO to -0.65 at T2 (P = 0.02), while the mean weight rose
      from 0.29 at T0 to 0.84 at T2, (P = 0.07). Six of 9 BMT adolescent girls
      experienced ovarian failure versus 0 of 11 girls treated with CT (P = 0.002).
      Seven adolescent CT males and seven BMT males showed normal pubertal progression.
      Two BMT patients require thyroid hormone supplementation, and one receives growth
      hormone. Six BMT patients and one CT patient developed cataracts, all of whom
      received irradiation (P = 0.10). Serum creatinine level, hypertension, or left
      ventricular shortening fraction were not different in the two groups. One BMT
      patient has chronic graft versus host disease. CONCLUSIONS: Growth, renal, and
      cardiac functions were similar in the two groups. The need for estrogen
      supplementation was more frequent following BMT. Recommendations concerning
      therapy for AML should depend on the probability of cure.

PMID- 10064183
TI  - Longitudinal clinical and functional pulmonary follow-up after megatherapy,
      fractionated total body irradiation, and autologous bone marrow transplantation
      for metastatic neuroblastoma.
AB  - BACKGROUND: A prospective follow-up was undertaken to document longitudinal
      changes in lung function in children with neuroblastoma treated with the Lyon
      Marseille-Curie-East of France Group protocol, consisting of high-dose
      chemotherapy schedules in combination with total body irradiation (TBI) and
      autologous bone marrow transplantation (ABMT), to determine the extent and timing
      of any changes seen and to describe late clinical and functional pulmonary
      sequelae. PROCEDURES: Eighteen children (1.5-6.9 years of age at TBI) performed
      pulmonary function tests (PFTs). These included measurement of functional
      residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn)
      and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or
      interstitial abnormalities. RESULTS: The clinical follow-up showed that
      bronchopulmonary symptoms occurred in 12 children. Three of them were clinically
      severely incapacitated. Serial PFTs showed an initial decrease of all mean values
      6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year.
      Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2
      years to 4 years after TBI with preservation of TLCO, suggesting restrictive
      ventilatory defects rather than pulmonary fibrosis. Individual analysis showed
      PFT defects in 100% of children 4 years after TBI. There was a higher incidence
      of lung pathology after two blocks of high-dose chemotherapy than after one block
      (100% versus 40%) and more severe sequelae. However these children had residual
      disease present after induction associated with lower baseline PFT. CONCLUSIONS:
      PFT defects were found in all children 4 years after TBI-ABMT, but they remained
      within acceptable limits except in very young children.

PMID- 10064184
TI  - Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75
      patients.
AB  - PURPOSE: This study was performed to describe prospectively the development and
      prognosis of severe ifosfamide-induced nephrotoxicity and to define the period of
      recommended renal follow-up after ifosfamide chemotherapy. PATIENTS AND METHODS:
      Renal function was followed in 75 patients after cessation of chemotherapy
      starting within the first year off therapy; median follow-up time was 31 months.
      The glomerular filtration rate was estimated by using the Schwartz formula.
      Proximal tubular transport capacities were evaluated for amino acids, phosphate,
      sodium, and glucose. In addition, serum bicarbonate level and alkaline
      phosphatase were measured. RESULTS: Five patients developed renal Fanconi
      syndrome during follow-up, and another seven patients developed a generalized
      subclinical tubulopathy. The latter condition always preceded Fanconi syndrome.
      Severe impairment of amino acid and phosphate reabsorption was seen in 28% and
      17.3% of patients, respectively. Reductions in amino acid reabsorption preceded
      impairment of phosphate reabsorption. In patients with early impairment of
      phosphate reabsorption, renal prognosis was poor, whereas normal or only mildly
      impaired amino acid handling virtually excluded progressive tubular damage.
      CONCLUSIONS: Ifosfamide-induced renal tubular damage is a potentially progressive
      disease. Along with measurement of phosphate reabsorption, additional assessment
      of tubular amino acid handling is suggested, because it allows early
      discrimination of poor from favorable renal outcomes.

PMID- 10064185
TI  - Hypersensitivity to carboplatin in children.
AB  - BACKGROUND: Hypersensitivity reactions are rare but at times severe complications
      to cytostatic drugs. PROCEDURE: The percentage of allergic reactions to
      carboplatin and their clinical features were evaluated in 185 children affected
      by different solid tumors and treated with etoposide-carboplatin chemotherapy.
      Allergic reactions that occurred during or immediately following etoposide
      infusion (5 cases, 2.8%) were excluded from the study. RESULTS: Seventeen out of
      185 patients (9.2%) suffered from allergic responses to carboplatin. The first of
      these occurred after an average of 10.1 courses (range, 1-23; median, 9). The
      risk calculated according to the number of courses is 2% at 6 courses, 11.3% at
      12 courses, and 47% at more than 12 courses. CONCLUSIONS: The high risk of
      allergic reactions to multiple courses of carboplatin should be kept in mind when
      developing treatment regimens that include the drug.

PMID- 10064186
TI  - Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for
      localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing
      Sarcoma Study.
AB  - BACKGROUND: The Cooperative Ewing Sarcoma Study (CESS 86), conducted by the
      German Society of Pediatric Oncology and Hematology (GPOH), was planned on the
      basis of the results of the preceding CESS 81 study. The prognostic significance
      of tumor volume in localized Ewing sarcoma of bone was well documented in the
      CESS 81 trial. As a consequence, the treatment intensity was adapted to volume in
      the follow-up CESS 86 trial: the four-drug combination used in CESS 81 was
      amended for patients with large tumor volume (> or = 100 ml), where ifosfamide
      was substituted for cyclophosphamide. PROCEDURE: From January 1986 to June 1991,
      177 protocol patients with localized Ewing sarcoma of bone were registered in
      CESS 86. The prognostic implication of tumor volume and several covariates was
      evaluated using Kaplan-Meier life table analysis and Cox's proportional hazard
      model. RESULTS: The estimated 5- and 8-year event-free survival (EFS) rates were
      both 59%. Age, gender, tumor site, and a tumor volume of 100 ml did not
      distinguish groups of patients with different prognosis. However, the prognosis
      of patients with tumors >200 ml (8-year EFS rate: 42%) was significantly inferior
      compared to patients with tumors both of 100 to 200 ml (70%) and of <100 ml
      (63%). In contrast to CESS 81, the histological response to chemotherapy was no
      longer a significant prognostic factor (EFS: 64% for good and 50% for poor
      responders, respectively). CONCLUSIONS: Despite risk-adapted treatment intensity,
      tumor volume retained its prognostic significance; the cut point, however, was
      shifted toward larger volumes.

PMID- 10064187
TI  - Screening for Wilms tumor in children with Beckwith-Wiedemann syndrome or
      idiopathic hemihypertrophy.
AB  - BACKGROUND: Children with Beckwith-Wiedemann syndrome and idiopathic
      hemihypertrophy (BWS/HH) are at increased risk for developing Wilms tumor and
      screening with abdominal sonography is frequently recommended. However, there is
      a paucity of published data supporting this strategy. The purpose of this study
      was to determine whether sonographic screening at intervals of 4 months or less
      reduced the proportion of late-stage Wilms Tumor (WT) in children with BWS/HH.
      PROCEDURE: A case series analysis was employed to compare the proportion of late
      stage (stage III or IV) Wilms tumor in patients with BWS/HH who were screened
      with sonography (n = 15) to the proportion of late-stage Wilms tumor in
      unscreened patients with BWS/HH (n = 59). Patients were identified from the BWS
      Registry and from previously published studies. Screened patients had sonograms
      at intervals of 4 months or less. RESULTS: None of the 12 screened children with
      Wilms tumor had late-stage disease, whereas 25 of 59 (42%) of unscreened children
      had late-stage Wilms tumor, a difference that was statistically significant (P <
      0.003). Three children had false positive screening studies. They were operated
      on for suspected Wilms tumor but the lesions proved to be complicated renal cysts
      (n = 2) or nephroblastomatosis (n = 1). CONCLUSIONS: This study suggests that
      children with BWS/HH may benefit from screening sonograms at intervals of 4
      months or less. However, false positive screening exams may result in unnecessary
      surgery. Given the rarity of BWS/HH, a larger, prospective international
      screening study is necessary to determine if the benefits of screening outweigh
      the risks.

PMID- 10064188
TI  - Clonal dissemination of T-lymphocytes in scid mice from familial hemophagocytic
      lymphohistiocytosis.
AB  - BACKGROUND: Although familial hemophagocytic lymphohistiocytosis (FHL) has been
      considered a disorder of T-cell dysfunction, there is no evidence of the clonal
      origin of T-cells in this disease. PROCEDURE: We engrafted mononuclear cells
      (MNCs) from five FHL patients into scid mice and examined the infiltration of
      human cells in mouse organs. The characterization of human cells that infiltrated
      in the mouse organs was then performed. RESULTS: A diffuse infiltration of human
      lymphoid cells was detected in scid mice treated with 1 x 10(6) MNCs from one of
      the five patients. These cells were positive for HLA-DR and CD3, but negative for
      CD4, CD8, CD20, and CD68, suggesting the infiltration of double negative (DN) T
      cells. The MNCs from the other four patients induced murine lymphoma-like
      disease; T-cell lymphoma in one and lymphoma of unknown origin in three. The
      characterization of these human DN T-cells was performed. The analysis of the
      Vbeta repertoire showed no preferential usage of the Vbeta family in MNCs, while
      the dominant expression of Vbeta13 was detected in T-cells infiltrating in the
      spleen and lung. A Jbeta analysis showed the restricted usage of Jbeta1.2 for
      Vbeta13 in these cells, and the clonality of Vbeta13-Jbeta1.2 fragment was
      confirmed by a single-strand confirmation polymorphism analysis. The analysis of
      the Valpha repertoire showed that Valpha24 was exclusively used in these DN T
      cells, but no usage of JalphaQ for Valpha24 was observed. CONCLUSIONS: A clonal
      expansion of T-cells was induced in scid mice by the engraftment of MNCs from an
      FHL patient. The infiltration of DN alphabeta T-cells bearing invariant Valpha24
      T-cell receptor in mouse organs may provide a useful clue to the pathogenesis of
      FHL. In the patients whose MNCs induced murine lymphoma-like disease, some
      cytokines or unknown factors that stimulate the growth and the tumorigenicity of
      murine lymphocytes might be produced by the MNCs engrafted in scid mice. Further
      study is needed to confirm the validity of our experimental approach and the
      findings observed in scid mice by using more FHL samples.

PMID- 10064189
TI  - Paclitaxel: an effective antineoplastic agent in the treatment of
      xenotransplanted hepatoblastoma.
AB  - BACKGROUND: Hepatoblastoma is an uncommon liver tumor of infancy and early
      childhood. Though most patients with nonmetastatic hepatoblastomas can be cured
      by defining surgical strategies and chemotherapy regimes, new drugs are needed
      for children with advanced hepatoblastomas. The activity of paclitaxel as a new
      antineoplastic agent with limited experience in pediatric oncology was studied in
      a xenograft model. PROCEDURE: Hepatoblastoma cell suspensions from three children
      were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary
      tumors was an embryonal multifocal hepatoblastoma, whereas the other tumors were
      embryonal/fetal hepatoblastomas localized on a liver lobe. After 4 weeks,
      xenografted tumor sizes reached 50-100 mm3. The xenografted tumors resembled
      their originals histologically and produced high levels of alpha-fetoprotein. The
      efficiency of paclitaxel at equitoxic doses was analyzed. RESULTS: Paclitaxel
      produced an effect in all three hepatoblastomas. There was a significant
      reduction of tumor volume (P < 0.001) and alpha-fetoprotein levels after
      chemotherapy (P < 0.0001). The proliferation activity of the tumor cells
      corresponded with these results. Histologically, after treatment with paclitaxel
      the tumor regression was 35%-49%. The mechanism of paclitaxel action could be
      demonstrated by light microscopy immunohistochemistry and electron microscopy.
      CONCLUSIONS: The preliminary results in phase I trials of solid tumors in
      children and the results of this study suggest that paclitaxel in phase II
      studies can now be entertained for patients with hepatoblastoma.

PMID- 10064190
TI  - "CNS-friendly" chemoradiotherapy in pediatric neuro-oncology.

PMID- 10064191
TI  - Music, medicine, and modus moriendi.

PMID- 10064192
TI  - Concurrent Langerhans cell histiocytosis and neuroblastoma.

PMID- 10064193
TI  - Ifosfamide/carboplatin/etoposide (ICE), an effective salvaging therapy for
      recurrent malignant non-Hodgkin lymphoma of childhood: a Pediatric Oncology Group
      phase II study.

PMID- 10064194
TI  - Composite carcinoma of the lung simulating small-cell carcinoma in a child.

PMID- 10064195
TI  - Non-Hodgkin lymphoma after heart-lung transplantation: response to chemotherapy.

PMID- 10064196
TI  - Reappearance of Hodgkin disease after 32 years: relapse or new disease?

PMID- 10064197
TI  - Head and neck teratoma in a neonate.

PMID- 10064198
TI  - 1998 Annual Histiocyte Society Abstracts, 14th Annual meeting. Kyoto, Japan, 30
      September-2 October 1998.

PMID- 10064199
TI  - Fatal maternal beta-hemolytic group B streptococcal meningitis: a case report.
AB  - Meningitis secondary to beta-hemolytic group B streptococcus is rare and
      represents less than 1% of cases of adult meningitis. We report the first known
      case of maternal mortality attributed to beta-hemolytic group B streptococcal
      meningitis. A 23-year-old African-American woman with a benign prenatal course
      delivered a viable male infant at term. Labor was complicated by thick meconium
      for which a saline amnioinfusion was utilized. On postpartum Day 1, the patient
      complained of right hip pain and a headache. Within 12 hr the patient was
      comatose with fixed and dilated pupils. Life support measures were discontinued
      secondary to absence of electrocortical activity. Postmortem examination revealed
      endomyometritis and fulminant meningitis with gram-positive cocci. Placental
      histologic sections demonstrated acute chorioamnionitis and bateriological
      cultures noted beta-hemolytic group B streptococcus. The virulence of beta
      hemolytic group B streptococcus in the neonate is well recognized. This case
      demonstrates that beta-hemolytic group B streptococcus is also a potentially
      fatal maternal pathogen.

PMID- 10064200
TI  - Favorable outcome in a fetus with an early-onset extensive cystic hygroma colli
      and intralesional hemorrhage.
AB  - We present a rare occurrence of an early-onset extensive cystic hygroma colli
      with intralesional hemorrhage and a favorable outcome. A 23-year-old primigravida
      woman was referred for management of a left isolated extensive cystic hygroma
      colli at 22 weeks' gestation. Amniocentesis revealed a 46, XY karyotype.
      Ultrasound-guidance in utero paracentesis was performed weekly or fortnightly
      from 22 to 36 gestational weeks. The aspirated fluid was chocolate-colored and
      contained abundant lymphocytes, erythrocytes, and protein. Despite multiple
      aspirations, the fetal cystic hygroma colli increased in size from 5.2x4.2 cm at
      22 weeks' gestation to 9x9.7 cm at 36 weeks' gestation. The woman underwent
      cesarean section at 36 week's gestation and a-2808 g neonate was born with a 10x6
      cm left neck mass, which did not impair spontaneous normal respiration. At the
      age of 4 days, the neonate underwent simple excision of the cystic hygroma, which
      was confined to the anterior superficial neck. The neonate was discharged 4 days
      after operation in good condition. In the present case, in utero paracentesis did
      not prevent the progressive growth of an early-onset extensive cystic hygroma
      colli with intralesional hemorrhage. However, lack of extension of the lesion
      into the surrounding structures and successful postnatal surgery contributed to
      the favorable outcome of this patient.

PMID- 10064201
TI  - Maternal serum placental isoferritin levels in pregnant women with abnormal
      uterine artery Doppler velocemitry.
AB  - High levels of placental isoferritin (PLF), which is an immunosuppressive
      cytokine, have been demonstrated in the sera of pregnant women. In the current
      study, 41 pregnant patients at high risk for placento-vascular complications,
      such as preeclamptic toxemia (PET) and/or intrauterine growth retardation (IUGR)
      were preselected if abnormal uterine artery Doppler measurements appeared at the
      time of the 20th-22nd gestational week scan. Concomitantly, venous blood was
      collected from each patient. PLF serum concentrations were determined by specific
      enzyme-linked immunoadsorbent assay (ELISA). The PLF levels were compared to 44
      healthy pregnant women at midgestation with uneventful pregnancy outcomes. The
      aim of the current study was to evaluate the contribution of PLF measurement in
      this preselected group. Following delivery, two subgroups of abnormal uterine
      artery Doppler waveforms were retrospectively defined. Twenty-one (51%) patients
      had normal outcomes, whereas 20 (49%) had pathological outcomes mainly
      complicated by PET and/or IUGR. Significant differences in PLF serum levels were
      observed between the control group (84+/-64 U/mL; median 84 U/mL) compared with
      those of the study subgroup with normal outcome (31+/-19 U/mL; median 23 U/mL)
      and with the pathological outcome subgroup (19+/-8 U/mL; median 17 U/mL)
      (p<0.05). Nineteen percent of the normal subgroup compared with 45% of the
      pathological subgroup were found to have a serum PLF concentration <19 U/mL. This
      cutoff level was achieved based on receiver operating characteristic (ROC) curve.
      The combination of abnormal uterine artery waveforms followed by low serum PLF
      <19 U/mL increased the positive predictive value to 63%, as compared with up to
      30% positive predictive value only for the abnormal Doppler waveforms. The
      current preliminary results concur with previous studies suggesting that low PLF
      levels may reflect abnormal placentation. The exact contribution of PLF and
      uterine artery Doppler waveforms in monitoring patients for placento-vascular
      complications should be the design of a future, larger, prospective study.

PMID- 10064202
TI  - Fetal fibronectin as a predictor of preterm birth: an overview.
AB  - The objective of this study was to determine if cervicovaginal fibronectin is
      predictive of preterm birth. Articles involving human subjects published in
      English between January 1976 and December 1997 were retrieved from MEDLINE using
      the keywords: fibronectin, fetal fibronectin, oncofetal fibronectin, preterm,
      PROM, preterm birth, and preterm labor. We included studies that were
      prospective, enrolled women at less than 37 weeks' gestation and blinded
      caregivers to the fetal fibronectin test results. Of the 24 studies meeting the
      inclusion criteria, 15 included symptomatic women; 8 included asymptomatic women;
      and 1 study included both. Data were abstracted independently by two authors and
      a meta-analysis of results of test characteristics, using summary values, was
      undertaken where possible. For symptomatic women, the sensitivity for delivery
      within 7 to 10 days of sampling was excellent (summary value [95% confidence
      interval ?CI?]: 98% [95%, 100%]). For delivery within 14 days, the sensitivity
      was somewhat lower (summary value [95% CI]: 82% [74%, 90%]) and lower still for
      delivery within 21 days (summary value [95% CI]: 73% [67%, 80%]). For delivery
      less than 34 weeks the sensitivity was good, but poor for delivery less than 37
      weeks (summary value [95% CI]: 87% [81%, 94%], 54% [51%, 58%] respectively). For
      asymptomatic women, the sensitivity of fetal fibronectin for delivery less than
      34 and less than 37 weeks was poor (summary value [95% CI]: 43% [36%, 50%] and
      64%[57%, 71%] respectively). The specificity of fetal fibronectin for symptomatic
      and asymptomatic women was over 80% for all outcomes. For symptomatic women, a
      negative test for fetal fibronectin should be useful at ruling out the likelihood
      of delivery within 7 to 10 days of sampling. For asymptomatic women, testing for
      fetal fibronectin is unlikely to be useful as many women at risk will be
      misclassified as normal.

PMID- 10064203
TI  - Diagnosis and differentiation of congenital diaphragmatic hernia from other
      noncardiac thoracic fetal masses.
AB  - This retrospective study was designed to evaluate individual sonographic
      parameters that might help differentiate congenital diaphragmatic hernia (CDH)
      from other noncardiac thoracic masses such as cystic adenomatoid malformation of
      the lung (CAML) and congenital lobar emphysema (CLE) prenatally. Twenty-four
      cases of CDH, CAML, and CLE detected during prenatal ultrasound and documented
      postnatally (with surgical, autopsy, or radiological proof) were identified
      through extensive chart and record review. The hard copy gray-scale images were
      retrospectively reviewed for imaging characteristics that may differentiate the
      three entities. Additionally, the prospective diagnosis during prenatal
      ultrasound was also compared with the postnatal diagnosis. The most reliable
      indicators in our retrospective review included confident visualization of a
      diaphragmatic defect (92.3/100.0 PPV/NPV, p< or =0.002) and/or localization of
      the stomach within the chest as well as the presence of severe cardiac deviation
      (both 92.3/62.5 PPV/NPV, p< or =0.01). Other sonographic indicators (including
      the presence of cystic areas, side and size of the lesion and the presence of
      polyhydramnios) offered lower levels of sensitivity and specificity. Prospective
      diagnosis during real-time assessment was also integral, offering >80%
      sensitivity and specificity (p< or =0.001). Accurate prenatal diagnosis of CDH is
      difficult despite the relative frequency of this lesion. The classic triad of a
      thoracic mass accompanying a displaced heart, absence of a normally positioned
      fluid-filled stomach and polyhydramnios, although seen with CDH, may not
      adequately differentiate this entity from other noncardiac fetal thoracic masses.
      Realtime assessment remains integral to the appropriate diagnosis.

PMID- 10064204
TI  - Sporadic congenital infantile cortical hyperostosis (Caffey's disease).
AB  - Prognosis of congenital infantile cortical hyperostosis (Caffey's disease) is
      poor particularly in premature babies. Two cases are presented of congenital
      Caffey's disease in premature babies. The first baby was hydropic at birth and
      had cortical hyperostosis involving the mandible and long bones of right upper
      limb and both lower limbs. The second baby had cortical hyperostosis of the nasal
      bones causing severe nasal nonchoanal stenosis that needed surgery, in addition
      to involvement of long bones of the four extremities. Both babies recovered from
      the disease and were discharged home well. These cases suggest that the improved
      outcome of congenital of infantile cortical hyperostosis may reflect improvement
      of neonatal mechanical ventilation and availability of neonatal total parenteral
      nutrition.

PMID- 10064205
TI  - The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or
      = 1000-gram infants.
AB  - We evaluated the effect of maternal magnesium sulfate treatment on selected
      neonatal outcomes in < or =1000-g infants. In a 1-year (1992-1993) observational
      study, the National Institute of Child Health and Human Development Network of
      Maternal-Fetal Medicine Units collected outcome data for 799 infants whose birth
      weights were < or =1000 g. Only singleton infants, with a gestational age >20
      weeks who were not the product of an induced abortion were included. Our analysis
      was further limited to those infants without major congenital anomalies, who were
      deemed potentially viable by the obstetrician, whose mother would have undergone
      a cesarean delivery for fetal indications, and who survived greater than 2 days.
      Outcomes were compared in infants whose mothers did and did not receive magnesium
      sulfate for labor tocolysis. Among the 124 women who did and the 184 who did not
      receive magnesium sulfate tocolytic therapy, the frequencies of grade III or IV
      intraventricular hemorrhage (16 vs. 20%, p = 0.34), seizure activity (7 vs. 10%,
      p = 0.35), grade III or IV retinopathy of prematurity (21 vs. 18% p = 0.59),
      abnormal neurological exam (28 vs. 28%, p = 0.91), intact survival to 120 days or
      to discharge (48 vs. 44%, p = 0.54), and infant mortality (23 vs. 31%, p = 0.10)
      were similar. Multiple logistic regression analysis was used to control for the
      effect of potential confounders (specifically, gestational age) and confirmed the
      lack of a significant association between maternal magnesium sulfate treatment
      for tocolysis and selected neonatal outcomes in this population of < or =1000
      gram infants.

PMID- 10064206
TI  - Liposomal amphotericin B in neonates with invasive candidiasis.
AB  - Liposomal amphotericin B (L-Amp B), a novel formulation of amphotericin B, is
      effective for the treatment of invasive fungal infections in children and adults
      and is associated with less toxicity than the conventional preparation. Data on
      the use of Liposomal amphotericin B in neonates is scarce. We describe the
      clinical course of two premature infants who were treated with Liposomal
      amphotericin B (one infant had candidemia, and the other had candidemia and
      meningitis), and provide a summary of previously published experience on this
      topic. Liposomal amphotericin B may be an option for therapy of invasive
      candidiasis in neonates who are at high risk of nephrotoxicity and other
      amphotericin-related reactions, but clinical trials are necessary to document its
      safety and efficacy in this age group.

PMID- 10064207
TI  - Lack of throat colonization with Burkholderia cepacia among cystic fibrosis
      healthcare workers.

PMID- 10064208
TI  - Should vancomycin susceptibility test be performed on enterococci isolated from
      nonsterile fluids or sites?

PMID- 10064209
TI  - Ways to avoid needle-hub contamination.

PMID- 10064210
TI  - Is a tuberculosis exposure a tuberculosis exposure if no one is infected?

PMID- 10064211
TI  - Look before you leap: discontinuation of an infusion therapy team.

PMID- 10064212
TI  - Infusion therapy team and dressing changes of central venous catheters.
AB  - OBJECTIVE: To determine whether central venous catheter (CVC) dressing changes
      could be performed by ward nurses rather than by the infusion therapy team (ITT)
      nurses without increasing the risk of catheter-related infection. DESIGN:
      Retrospective cohort study using prospectively collected data. The study extended
      from January 1995 to June 1996. SETTING: The University of Texas M.D. Anderson
      Cancer Center, a referral cancer center. PATIENTS: The study group was a random
      sample of 483 patients who received CVC dressing changes by ward nurses during
      the study period. A random sample of 483 patients who received CVC dressing
      changes by the ITT constituted the control group. RESULTS: The risks of catheter
      related septicemia were 1.7% among cases and 1.4% among controls (risk ratio,
      1.14; 95% confidence interval [CI95], 0.26-6.42; P=.70). There also were no
      significant differences between the two groups in the risks of catheter-related
      site infection (risk ratio, 0.50; CI95, 0.02-4.12; P=.25) or any catheter-related
      infection (risk ratio=1.00; CI95, 0.27-3.64; P=.59). CONCLUSIONS: Provided that
      aseptic techniques (including maximal barrier precautions during insertion) are
      maintained, the responsibility of CVC dressing changes could be delegated to the
      ward nurses without increasing the low risk of CVC-related infection, resulting
      in an estimated cost saving in excess of $90,000 per year.

PMID- 10064213
TI  - Control of vancomycin-resistant enterococci at a community hospital: efficacy of
      patient and staff cohorting.
AB  - OBJECTIVE: To evaluate the efficacy of patient and staff cohorting to control
      vancomycin-resistant enterococci (VRE) at an Indianapolis community hospital.
      DESIGN: To interrupt transmission of VRE, a VRE point-prevalence survey of
      hospital inpatients was conducted, and VRE-infected or -colonized patients were
      cohorted on a single ward with dedicated nursing staff and patient-care
      equipment. To assess the impact of the intervention, staff compliance with
      contact isolation procedures was observed, and the VRE point-prevalence survey
      was repeated 2 months after the cohort ward was established. RESULTS: Following
      the establishment of the cohort ward, VRE prevalence among all hospitalized
      inpatients decreased from 8.1% to 4.7% (25 positive cultures among 310 patients
      compared to 13 positive cultures among 276 patients, P=.14); VRE prevalence among
      patients whose VRE status was unknown before cultures were obtained decreased
      from 5.9% to 0.8% (18 positive cultures among 303 patients compared to 2 positive
      cultures among 262 patients, P=.002); and observed staff-patient interactions
      compliant with published isolation recommendations increased (5 [22%] of 23
      interactions compared to 36 [88%] of 41 interactions, P<.0001). CONCLUSIONS: Our
      data suggest that, in hospitals with endemic VRE or continued VRE transmission
      despite implementation of contact isolation measures, establishing a VRE cohort
      ward may be a practical and effective method to improve compliance with infection
      control measures and thereby to control epidemic or endemic VRE transmission.

PMID- 10064214
TI  - Use of personal protective equipment and operating room behaviors in four
      surgical subspecialties: personal protective equipment and behaviors in surgery.
AB  - OBJECTIVE: To evaluate Universal Precautions (UP) compliance in the operating
      room (OR). DESIGN: Prospective observational cohort. Trained observers recorded
      information about (1) personal protective equipment used by OR staff; (2)
      eyewear, glove, or gown breaks; (3) the nature of sharps transfers; (4) risk
      taking behaviors of the OR staff; and (5) needlestick injuries and other blood
      and body-fluid exposures. SETTING: Barnes-Jewish Hospital, a 1,000-bed, tertiary
      care hospital affiliated with Washington University School of Medicine, St Louis,
      Missouri. PARTICIPANTS: OR personnel in four surgical specialties (gynecologic,
      orthopedic, cardiothoracic, and general). Procedures eligible for the study were
      selected randomly. Hand surgery and procedures requiring no or a very small
      incision (eg, arthroscopy, laparoscopy) were excluded. RESULTS: A total of 597
      healthcare workers' procedures were observed in 76 surgical cases (200 hours). Of
      the 597 healthcare workers, 32% wore regular glasses, and 24% used no eye
      protection. Scrub nurses and medical students were more likely than other
      healthcare workers to wear goggles. Only 28% of healthcare workers double gloved,
      with orthopedic surgery personnel being the most compliant. Sharps passages were
      not announced in 91% of the surgical procedures. In 65 cases (86%), sharps were
      adjusted manually. Three percutaneous and 14 cutaneous exposures occurred, for a
      total exposure rate of 22%. CONCLUSION: OR personnel had poor compliance with UP.
      Although there was significant variation in use of personal protective equipment
      between groups, the total exposure rate was high (22%), indicating the need for
      further training and reinforcement of UP to reduce occupational exposures.

PMID- 10064215
TI  - Transmission of measles virus in healthcare settings during a communitywide
      outbreak.
AB  - OBJECTIVE: To describe the epidemiology of measles in medical settings and to
      evaluate the implementation and effectiveness of the 1989 Advisory Committee on
      Immunization Practices (ACIP) guidelines for measles immunization in healthcare
      workers (HCWs). DESIGN: Confirmed cases of measles reported in Clark County,
      Washington, from March 14 to June 2, 1996, were analyzed for characteristics of
      cases occurring in medical settings. A questionnaire was used to assess employee
      immunization (95% response rate). SETTING AND PARTICIPANTS: Reported measles
      cases and HCWs at community hospitals, primary-care medical facilities, a health
      maintenance organization, and a multispecialty group practice. RESULTS: Of 31
      cases of measles, 8 (26%) occurred in HCWs, and 5 (16%) occurred in patients or
      visitors to medical facilities. Cases of measles occurred in HCWs who were not
      required to have proof of measles immunity as defined by the 1989 ACIP
      guidelines. The relative risk of measles in HCWs compared to Clark County adults
      was 18.6 (95% confidence interval, 7.4-45.8; P<.001). A survey of medical
      facilities revealed that 47% had an employee measles immunization policy; only
      21% met ACIP recommendations and enforced their policies. CONCLUSIONS: HCWs were
      at higher risk of measles than the adult population. Transmission of measles in
      medical settings was related to both deficiencies in, and lack of implementation
      of, the ACIP guidelines.

PMID- 10064216
TI  - Incidence of pertussis infection in healthcare workers.
AB  - OBJECTIVE: To determine the incidence of pertussis infection in two groups of
      healthcare workers. DESIGN: Retrospective cohort study. SETTING: 660-bed, urban,
      tertiary-care university hospital. PARTICIPANTS: 106 resident physicians and 39
      emergency department employees. INTERVENTIONS: Antibodies to pertussis toxin and
      filamentous hemagglutinin were determined in fresh serum specimens and in stored
      sera collected 1 to 3 years previously. A 50% rise in both the pertussis toxin
      and filamentous hemagglutinin from the initial to the follow-up specimen was
      considered diagnostic of a pertussis infection. RESULTS: Two of 106 residents had
      serological evidence of a pertussis infection during 151.3 subject-observation
      years, for an annual incidence rate of 1.3% (95% confidence interval [CI95], 0%
      3.5%). Three of 39 emergency department employees had serological evidence of a
      pertussis infection during 81.2 subject-observation years, for an annual
      incidence of 3.6% (CI95, 0%-9.6%). Of these 5 subjects, 2 had symptomatic
      disease. CONCLUSION: We found both symptomatic and asymptomatic pertussis
      infections in two cohorts of healthcare workers. Although the incidence rates
      were somewhat lower than found in other studies, they nonetheless were higher
      than for almost all other diseases for which we vaccinate healthcare workers. Our
      results would support the use of acellular pertussis vaccine in healthcare
      workers.

PMID- 10064217
TI  - How many nosocomial infections are missed if identification is restricted to
      patients with either microbiology reports or antibiotic administration?
AB  - OBJECTIVE: To investigate how many nosocomial infections would be missed if
      surveillance activities were restricted to patients having either microbiology
      reports or antibiotic administration. DESIGN: Analysis of data from a large
      prevalence study on nosocomial infections (Nosocomial Infections in Germany
      Surveillance and Prevention). SETTING: A total of 14,966 patients were
      investigated in medical, surgical, obstetric-gynecologic, and intensive-care
      units of 72 German hospitals representatively selected according to size. Five
      hundred eighteen patients (3.5%) had at least one nosocomial infection.
      Microbiology reports were available for 56.6% of these patients on the prevalence
      day, and 86.3% received antibiotics. RESULTS: Only 31 nosocomially infected
      patients (6%) would have been missed by using either microbiology reports or
      antibiotic treatment as an indicator. These indicators of nosocomial infections
      had a high diagnostic sensitivity for nosocomial pneumonia (98.8%), urinary tract
      infections (96.3%), and primary bloodstream infections (95.3%), but a lower
      sensitivity for wound infections (85.4%). Thus, 97.4% of all nosocomial
      infections were found with this method in intensive-care units and 96.1% in
      medicine units, but only 89.7% in surgical departments. In 9 (12.5%) of 72
      hospitals, the overall sensitivity would have been <80% using a combination of
      the two indicators. For this reason, the situation in one's own hospital should
      be checked before using this method. CONCLUSIONS: After checking the situation in
      one's own hospital, the "either-or" approach using the two indicators
      "microbiology report" and "antibiotic administration" can be recommended as a
      time-saving measure to diagnose pneumonia, urinary tract, and primary bloodstream
      infections. For wound infections, additional information obtained by changing
      dressings or participating in ward rounds is necessary to achieve satisfactory
      sensitivity in the surveillance of nosocomial infections. Of course, it is
      necessary that the surveillance staff discard all false positives to ensure a
      satisfactory specificity.

PMID- 10064218
TI  - Investigation of suspected nosocomial clusters of Staphylococcus haemolyticus
      infections.
AB  - OBJECTIVE: To determine whether typing methods can discriminate among
      Staphylococcus haemolyticus isolates. DESIGN: Molecular epidemiological
      evaluation of S. haemolyticus isolates obtained from patients hospitalized on a
      hematology service and in a surgical intensive-care unit (SICU). SETTING: A large
      Midwestern teaching hospital. INTERVENTIONS: None. RESULTS: Over 22 days, S.
      haemolyticus was isolated from five patients on the hematology service. Isolates
      from four patients had the same unusual antibiogram and biotype. Ribotyping,
      restriction endonuclease digestion of plasmid DNA (REAP), and whole chromosomal
      DNA analysis by pulsed-field gel electrophoresis (PFGE) confirmed that these
      isolates were identical and different from the fifth patient's isolate and from 6
      control isolates. In a second cluster, 11 S. haemolyticus isolates obtained from
      eight patients in the SICU had similar antibiograms and biotypes. By REAP and
      ribotype analysis, isolates from four patients were identical. However, PFGE
      indicated that only two of these patients shared a common strain. CONCLUSIONS:
      Antibiograms or biotyping may discriminate among isolates of S. haemolyticus if
      the results of these tests are unusual. Many clinical isolates can be
      differentiated by REAP analysis, ribotyping, or PFGE. However, some isolates are
      identical by all of these methods, suggesting that they may have been transmitted
      nosocomially.

PMID- 10064219
TI  - Donor-to-recipient transmission of bacteria as an unusual cause of mediastinitis
      in a heart transplant recipient.
AB  - We present a 54-year-old male heart transplant recipient who developed
      mediastinitis caused by Klebsiella oxytoca and Veillonella species. Culture of
      the donor's bronchus also grew K. oxytoca and a Veillonella species. Pulsed-field
      gel electrophoresis revealed that the K. oxytoca isolates had identical banding
      patterns. This case illustrates transmission of pathogenic bacteria via a
      contaminated organ.

PMID- 10064220
TI  - The continuing evolution of methicillin-resistant Staphylococcus aureus in
      Western Australia.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been notifiable in Western
      Australia since 1985. This article reviews the notification data from 1994 to
      1997, focusing on increases in MRSA notifications and the proportion that are
      local strains; changes in the geographical distribution of MRSA; and changes in
      antibiotic-resistance patterns.

PMID- 10064221
TI  - Selecting respirators for control of worker exposure to infectious aerosols.
AB  - A method for selecting respirators for protection in infectious aerosol
      environments was developed, building on a procedure used to choose respiratory
      protection for environments containing nonbiological contaminants. Modifications
      in the traditional respirator selection method are proposed for situations where
      information on occupational exposure limits, toxicity, and airborne
      concentrations is absent. Toxicity is determined from risk rankings proposed by a
      variety of organizations. The nature of the activity allows assessment of source
      generation, which is combined with room volume and airflow to obtain a ranking of
      airborne concentration. Finally, concentration and toxicity ranks determine a
      minimum assigned protection factor, which corresponds to a respirator class. Case
      studies are presented to illustrate the proposed decision logic. For each
      situation, the procedure yielded choices that were both protective and
      reasonable. These results suggest that the procedure will be applicable to a
      variety of settings for a range of infectious organisms.

PMID- 10064222
TI  - Kawasaki syndrome.
AB  - KS is a fascinating illness of childhood that has emerged over the last 30 years
      and is now recognized as the most common cause of acquired heart disease in
      children in the United States. It has a dramatic clinical presentation in most
      cases, but for a small number of cases that present with a more subtle disease
      there appears to be a greater risk of coronary artery complications. Progress has
      been made in the management of KS, but although the disease appears to be related
      to an infectious etiology, no infectious agent has been proven to be the cause.
      Finally, issues in long-term management and prognosis are yet to be clarified.

PMID- 10064223
TI  - Introduction: acute respiratory tract infections--the forgotten pandemic.

PMID- 10064224
TI  - Respiratory tract infections as a public health challenge.
AB  - Acute respiratory infections have everywhere become the province of clinicians
      and the pharmaceutical industry. A public health approach is needed with
      systematic efforts to minimize transmission, maximize prevention, and harness the
      research and surveillance effort to decrease their incidence and severity. These
      infections have a huge incidence, morbidity burden, and economic impact in all
      societies. Several factors now demand renewed attention to prevention. They
      include the growing costs and potentially limited benefits of an expanded
      pharmacotherapeutic approach; the serious change in antibiotic susceptibility of
      the common respiratory pathogens; the advances made in vaccinology in recent
      years; and the need to promote equity and share limited health resources across
      the world's population. Care should not be restricted to those in affluent
      countries who can afford increasingly expensive treatment.

PMID- 10064225
TI  - A national program for control of acute respiratory tract infections: the
      Philippine experience.
AB  - Maturing programs on child immunization and diarrheal diseases, a community-based
      research project, and a rational drug-use program facilitated the launching in
      1989 of a nationwide Philippine Control of Acute Respiratory Infections program
      (Phil-CARI). From 1990 to 1991 the Phil-CARI expanded rapidly, training >80% of
      its middle managers and frontline health care providers on the case-management
      protocols of the World Health Organization for acute respiratory infection.
      Multiple donors and good collaboration with various societies and medical schools
      assisted the program. However, by 1992, there were difficulties in maintaining
      training quality, follow-up, and supervision. Donor assistance dwindled and the
      health care delivery system decentralized. Government procurement systems were
      unable to meet the logistics demands of the program. The monitoring and
      evaluation system was inadequate to measure impact. The Phil-CARI provides
      lessons in searching for more sustainable approaches and systems to meet the
      various demands of a nationwide ARI control program and to create the desired
      impact.

PMID- 10064226
TI  - Interrupting the transmission of respiratory tract infections: theory and
      practice.
AB  - Interruption of transmission has always been one of the most attractive
      approaches for infection control. The technologies available were severely
      limited before the development of appropriate vaccines. Mathematically, the
      proportion of those who need to be immune to interrupt transmission can be
      derived from the Ro, which represents the number of new cases infected by a
      single case when all contacts are susceptible. Purely respiratory infections have
      critical characteristics affecting transmission that are different from key
      childhood vaccine-preventable diseases spread by the respiratory route. They
      include frequent reinfections and antigenic changes of the agents. Pragmatic
      approaches to understanding their potential effect can be found in experimental
      and programmatic use of vaccines such as those for Haemophilus influenzae type b
      and influenza virus infections. Results of these experiences can in turn
      strengthen the development of transmission theory.

PMID- 10064227
TI  - Epidemiology and prevention of group A streptococcal infections: acute
      respiratory tract infections, skin infections, and their sequelae at the close of
      the twentieth century.
AB  - Infections of the upper respiratory tract and skin due to group A Streptococcus
      are common, and the organism is highly transmissible. In industrialized countries
      and to some extent in developing countries, control efforts continue to emphasize
      that group A streptococcal pharyngitis should be properly diagnosed and
      appropriately treated. In developing countries and in indigenous populations
      where the burden of group A streptococcal diseases appears greatest, the
      epidemiology is less completely defined and may differ from that in
      industrialized countries. There is a need for accurately collected
      epidemiological data from developing countries, which may also further clarify
      the pathogenesis of group A streptococcal infections and their sequelae. While
      proper treatment of group A streptococcal pharyngitis continues to be essential
      in all populations, it may be appropriate in developing countries to consider
      additional strategies to reduce rates of pyoderma.

PMID- 10064228
TI  - Preventing the spread of antimicrobial resistance among bacterial respiratory
      pathogens in industrialized countries: the case for judicious antimicrobial use.
AB  - The spread of antimicrobial resistance is an important emerging health threat in
      developed countries. Widespread outpatient antimicrobial use leads to the spread
      of resistance among community-acquired pathogens such as Streptococcus
      pneumoniae. The Centers for Disease Control and Prevention and partner
      organizations have initiated a national campaign promoting more judicious
      antimicrobial use to decrease the spread of resistance. The initial focus is to
      improve management of respiratory tract infections, which account for most
      outpatient antimicrobial use. Survey and focus group results indicate that
      patient pressure and suboptimal diagnosis and treatment contribute to antibiotic
      overuse. To educate physicians, a series of "principles of judicious antibiotic
      use" have been developed that identify optimal approaches to management of common
      respiratory infections. Patient education materials and strategies to improve
      doctor-patient communication also have been developed. Several studies currently
      under way will evaluate the impact of intervention on antibiotic use practices
      and resistant carriage or infection.

PMID- 10064229
TI  - Antibiotic strategies for developing countries: experience with acute respiratory
      tract infections in Pakistan.
AB  - The Pakistan program for control of acute respiratory tract infections (ARIs)
      adopted the standard ARI-case-management strategy of the World Health
      Organization and recommended co-trimoxazole for the management of nonsevere
      pneumonia. Reports in that country of high in vitro antimicrobial resistance of
      Streptococcus pneumoniae and Haemophilus influenzae to co-trimoxazole prompted
      the program to reevaluate its treatment policy. Two community-based studies
      during 1991-1993 showed in vivo efficacy of co-trimoxazole in 92% and 91% of
      children with nonsevere pneumonia. A third double-blind trial showed co
      trimoxazole and oral amoxicillin to be equally effective in vivo in cases of
      nonsevere pneumonia, despite high in vitro resistance. Country-wide surveillance
      from 1991 to 1994 revealed 78.3%-79.9% in vitro resistance to co-trimoxazole
      among S. pneumoniae isolates and 59.5%-61.0% among H. influenzae isolates. Co
      trimoxazole is still recommended by the Pakistan ARI control program. The fact
      that amoxicillin is three times more expensive and must be administered more
      frequently is a big impediment to recommending it as a first-line drug for
      nonsevere pneumonia.

PMID- 10064230
TI  - Maternal immunization.
AB  - Maternal immunization can enhance passive immunity of infants to pathogens that
      cause life-threatening illnesses. In most instances, immunization during
      pregnancy will provide important protection for the woman as well as for her
      offspring. The tetanus toxoid and influenza vaccines are examples of vaccines
      that provide a double benefit. Other vaccines under evaluation include those for
      respiratory syncytial virus, pneumococci, group B streptococci, and Haemophilus
      influenzae type b. Although most IgG antibody crosses the placenta in the third
      trimester, the process is time-dependent, dictating that immunization should be
      accomplished ideally at least 6 weeks prior to delivery. IgG1 antibodies are
      transferred preferentially. Maternal immunization has not interfered with active
      immunization of the infant. Inactivated vaccines administered in the third
      trimester of pregnancy pose no known risk to the woman or to her fetus.

PMID- 10064231
TI  - Potential advantages of DNA immunization for influenza epidemic and pandemic
      planning.
AB  - Immunization with purified DNA is a powerful technique for inducing immune
      responses. The concept of DNA immunization involves insertion of the gene
      encoding the antigen of choice into a bacterial plasmid and injection of the
      plasmid into the host where the antigen is expressed and where it induces humoral
      and cellular immunity. The most effective routes and methods for DNA immunization
      are bombardment with particles coated with DNA ("gene gun" technique), followed
      by the intramuscular and intradermal routes. DNA immunization technology has the
      potential to induce immunity to all antigens that can be completely encoded in
      DNA, which therefore include all protein, but not carbohydrate, antigens. DNA
      immunization results in presentation of antigens to the host's immune system in a
      natural form, like that achieved with live-attenuated vaccines. The DNA
      immunization strategy has the potential to rapidly provide a new vaccine in the
      face of an emerging influenza pandemic.

PMID- 10064232
TI  - The future role of international agencies in control of acute respiratory tract
      infections.
AB  - Achievements in the control of acute respiratory infection (ARI) owe much to
      international collaboration in research, education, and delivery of services.
      This article highlights some of the current activities of the many international
      agencies involved and summarizes thoughts on their future roles. Key recent
      scientific advances include better surveillance, new and improved vaccines,
      refinement of standard clinical management plans and behavioral change
      techniques, and demonstration of the effectiveness of their application. Agencies
      involved include the World Health Organization, the International Union Against
      Tuberculosis and Lung Disease, national government agencies for overseas aid,
      many academic departments, and professional lung health associations. However,
      much remains to be done, especially in collaborative research, in the devising,
      implementing, and evaluating of health care delivery systems in low-income
      countries, and in mobilizing political will and resources. These are tasks beyond
      the capacity of any lone agency. Success will depend on how effectively we
      collaborate.

PMID- 10064233
TI  - Care-seeking behavior.

PMID- 10064234
TI  - Chinese Herbal Medicine in the treatment of acute respiratory tract infections:
      review of randomized and controlled clinical trials.

PMID- 10064235
TI  - Mycoplasma pneumoniae pneumonia: current perspectives.

PMID- 10064236
TI  - Towards a protein vaccine for nontypeable Haemophilus influenzae.

PMID- 10064237
TI  - Photo quiz. Aberrant fat deposition (benign lipomatosis) in association with
      highly active antiretroviral therapy.

PMID- 10064238
TI  - Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant
      recipients ever be discontinued?
AB  - Solid organ transplant recipients are at risk for Pneumocystis carinii pneumonia
      (PCP), but the risk of PCP beyond 1 year is poorly defined. We identified 25
      cases of PCP in 1,299 patients undergoing solid organ transplantation between
      1987 and 1996 at The Cleveland Clinic Foundation (4.8 cases per 1,000 person
      transplant-years [PTY]). Ten (36%) of 28 PCP cases (transplantation was performed
      before 1987 in three cases) occurred > or = 1 year after transplantation, and no
      patient developed PCP while receiving prophylaxis for PCP. The incidence of PCP
      during the first year following transplantation was eight times higher than that
      during subsequent years. The highest rate occurred among lung transplant
      recipients (22 cases per 1,000 PTY), for whom the incidence did not decline
      beyond the first year of transplantation. We conclude that the incidence of PCP
      is highest during the first year after transplantation and differs by type of
      solid organ transplant. Extending the duration of PCP prophylaxis beyond 1 year
      may be warranted for lung transplant recipients.

PMID- 10064239
TI  - Editorial response: Prophylaxis for Pneumocystis carinii pneumonia in solid organ
      transplant recipients--as long as the pros outweigh the cons.

PMID- 10064240
TI  - Itraconazole oral solution as prophylaxis for fungal infections in neutropenic
      patients with hematologic malignancies: a randomized, placebo-controlled, double
      blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie
      Ematologiche dell' Adulto.
AB  - To evaluate the efficacy and safety of itraconazole oral solution for preventing
      fungal infections, a randomized, placebo-controlled, double-blind, multicenter
      trial was conducted: 405 neutropenic patients with hematologic malignancies were
      randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201
      patients), or placebo (204 patients). Proven and suspected deep fungal infection
      occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a
      difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P
      = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole
      recipients and in 4% of placebo recipients, a difference of 3.5 percentage points
      (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the
      itraconazole recipients compared with 4 placebo recipients, a difference of 2
      percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was
      documented in four itraconazole recipients (one death) and one placebo recipient
      (one death). Side effects causing drug interruption occurred in 18% of
      itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution
      was well-tolerated and effectively prevented proven and suspected deep fungal
      infection as well as systemic infection and death due to Candida species.

PMID- 10064241
TI  - Early infection in bone marrow transplantation: quantitative study of clinical
      factors that affect risk.
AB  - Infections remain common life-threatening complications of bone marrow
      transplantation. To examine clinical factors that affect infection risk, we
      retrospectively studied patients who received bone marrow transplants (53
      autologous and 51 allogeneic). Over a median of 27 hospital days, 44 patients
      developed documented infections. Both autologous transplantation and
      hematopoietic growth factor use were associated with less prolonged neutropenia
      and decreased occurrence of infection (P < or = .05). In a survival regression
      model, variables independently associated with infection risk were the log10 of
      the neutrophil count (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.32
      0.75), ciprofloxacin prophylaxis (HR, 0.42; 95% CI, 0.19-0.95), empirical
      intravenous antibiotic use (HR, 0.09; 95% CI, 0.03-0.32), and an interaction
      between neutrophil count and intravenous antibiotic use (HR, 1.86; 95% CI, 1.06
      3.29). In this model, infection risk increases steeply at low neutrophil counts
      for patients receiving no antibiotic therapy. Ciprofloxacin prophylaxis and
      particularly intravenous antibiotic therapy provide substantial protection at low
      neutrophil counts. These results can be used to model management strategies for
      transplant recipients.

PMID- 10064242
TI  - Outer membrane protein profiles of paired nasopharyngeal and middle ear isolates
      of nontypable Haemophilus influenzae from Mexican children with acute otitis
      media.
AB  - We studied nontypable Haemophilus influenzae (NTHi) isolates from simultaneous
      cultures of nasopharyngeal exudates (NEs) and middle ear fluids (MEFs) obtained
      by tympanocentesis from 57 children with acute otitis media (AOM). Preparations
      of outer membrane proteins (OMPs) from 14 pairs of NTHi strains recovered from
      NEs and MEFs from 10 children with unilateral AOM and four with bilateral AOM
      were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. The
      NTHi subtypes were determined by comparing the OMP profiles of the isolated
      strains with those of eight reference NTHi subtypes. Of the 14 pairs, 10 (71%)
      were identical, and one (8%) was different; three strains isolated from NEs (21%)
      did not correspond to any of the reference subtypes (nonsubtypable). Subtypes 4,
      6, 5, 3, and 8 were isolated in the present study, thereby showing that their
      distribution is similar to that of subtypes isolated from children with AOM in
      the United States and suggesting that common otogenic strains are widely
      distributed in North America.

PMID- 10064243
TI  - Cat-scratch disease with paravertebral mass and osteomyelitis.
AB  - The case of a 9-year-old girl with cat-scratch disease (CSD) complicated by
      development of a paravertebral mass and osteomyelitis is presented. Following
      multiple scratches and inguinal lymphadenopathy, she developed back pain, and
      imaging demonstrated a paravertebral mass with evidence of osteomyelitis
      involving vertebra T9. The diagnosis was made on the basis of detection of
      Bartonella henselae by use of molecular techniques on an aspirate from the
      vertebral column and supportive serology for infection with B. henselae. Eleven
      other cases of this unusual manifestation associated with CSD have been reported
      in the literature and are reviewed. The patient was treated with gentamicin,
      followed by rifampicin and trimethoprim-sulfamethoxazole, orally and made a
      favorable recovery over 7 months. This is comparable with other case reports,
      regardless of the choice of antibiotic therapy. CSD in immunocompetent hosts is
      not always self-limiting, and tissues beyond the lymph nodes can be involved.

PMID- 10064244
TI  - Natural history of Helicobacter pylori infection in childhood: 12-year follow-up
      cohort study in a biracial community.
AB  - We assessed the pattern of acquisition and loss of Helicobacter pylori infection
      in a cohort of 212 children from a biracial community with a homogeneous
      socioeconomic class. The children were followed over 12 years (1973-1974 to 1985
      1986) from childhood to young adulthood. H. pylori status was assessed by the
      presence of serum IgG antibodies to H. pylori. At ages 7-9, 19% of children had
      H. pylori infection (40% of blacks vs. 11% of whites; P = .0001); 12 years later,
      33% were seropositive. The higher prevalence among blacks remained (P = .0001).
      During follow-up, 22% of children became infected; the rate of acquisition was
      fourfold greater among blacks than among whites (P = .001). Over the 12-year
      period, infection was lost in 50% of whites compared with 4% of blacks who either
      remained infected or became reinfected. H. pylori infection in childhood is
      affected by both acquisition and loss of infection in different ethnic groups.
      This observation is critical for understanding the epidemiology and transmission
      of H. pylori infection.

PMID- 10064245
TI  - Evaluation of clinical case definitions of influenza: detailed investigation of
      patients during the 1995-1996 epidemic in France.
AB  - Using clinical predictors, we evaluated clinical case definitions of influenza
      during the 1995-1996 outbreak in France. Thirty-five general practitioners
      collected virological specimens and clinical data. Predictors of influenza virus
      infection were selected with logistic regression models. The results varied with
      the influenza virus subtype: temperature of >38.2 degrees C, stiffness or
      myalgia, rhinorrhea, and cough were predictive of influenza A/H3N2, whereas
      fatigue, lacrimation or conjunctival injection, and the absence of stiffness or
      myalgia were predictive of influenza A/H1N1. On the basis of this analysis and
      data from the literature, 12 clinical case definitions were evaluated for their
      abilities to diagnose influenza virus infection. They were associated with
      positive predictive values of 27% to 40% and negative predictive values of 80% to
      91%. We conclude that focused studies evaluating clinical case definitions of
      influenza with use of subsets of patients should accompany population-based
      disease surveillance for optimal estimates of the disease burden associated with
      influenza epidemics.

PMID- 10064246
TI  - A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS
      associated cryptococcal meningitis. National Institute of Allergy and Infectious
      Diseases Mycoses Study Group.
AB  - This study was designed to compare the effectiveness of fluconazole vs.
      itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis.
      HIV-infected patients who had been successfully treated (achieved negative
      culture of CSF) for a first episode of cryptococcal meningitis were randomized to
      receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study
      was stopped prematurely on the recommendation of an independent Data Safety and
      Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had
      experienced culture-positive relapse, compared with 2 relapses (4%) noted among
      51 fluconazole recipients (P = .006). The factor best associated with relapse was
      the patient having not received flucytosine during the initial 2 weeks of primary
      treatment for cryptococcal disease (relative risk = 5.88; 95% confidence
      interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for
      maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may
      contribute to the prevention of relapse if used during the first 2 weeks of
      primary therapy.

PMID- 10064247
TI  - Editorial response: A comparison of itraconazole versus fluconazole as
      maintenance therapy for AIDS-associated cryptococcal meningitis.

PMID- 10064248
TI  - Safety of long-term therapy with ciprofloxacin: data analysis of controlled
      clinical trials and review.
AB  - We reviewed the literature and the manufacturer's U.S. clinical data pool for
      safety data on long-term administration of ciprofloxacin (Bayer, West Haven, CT).
      Only controlled clinical trials including patients treated for >30 days were
      selected. We identified 636 patients by literature search and 413 patients in the
      Bayer U.S. database who fulfilled our search criteria; the average treatment
      duration for these patients was 130 and 80 days, respectively. Main indications
      for long-term therapy were osteomyelitis, skin and soft-tissue infection,
      prophylaxis for urinary tract infection, mycobacterial infections, and
      inflammatory bowel disease. Adverse events, premature discontinuation of therapy,
      and deaths occurred at a similar frequency in both treatment arms. Most adverse
      events occurred early during therapy with little increase in frequency over time.
      As with short-term therapy, gastrointestinal events were more frequent than
      central nervous system or skin reactions, but pseudomembranous colitis was not
      observed. No previously unknown adverse events were noted. We conclude that
      ciprofloxacin is tolerated as well as other antibiotics when extended courses of
      therapy are required.

PMID- 10064249
TI  - Cryptococcosis in children with AIDS.
AB  - We compiled the clinical and immunologic features of Cryptococcus neoformans
      infections in human immunodeficiency virus (HIV)-infected children from 1985 to
      1996 in a retrospective case series. Thirty cases of cryptococcosis were
      identified. These children had a median age of 9.8 years, a median CD4+ cell
      count of 54/microL at the time of diagnosis, and either a culture positive for C.
      neoformans or cryptococcal antigen in serum or cerebrospinal fluid. Sixty-three
      percent of the cases occurred in children vertically infected with HIV and in
      children between 6 and 12 years of age. The clinical and laboratory
      characteristics of this pediatric cohort were similar to those of adults with
      AIDS and cryptococcosis. On the basis of a subset of the cases, a 10-year point
      prevalence of cryptococcosis among children with AIDS of approximately 1% was
      estimated.

PMID- 10064250
TI  - Cryptosporidium, enterocytozoon, and cyclospora infections in pediatric and adult
      patients with diarrhea in Tanzania.
AB  - Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four
      groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children
      with chronic diarrhea (of whom 23 of 59 were positive [+] for human
      immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55
      were HIV+), and HIV control children without diarrhea. Cryptosporidium was
      identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea
      (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control
      children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were
      malnourished, compared with 10/48 without cryptosporidiosis (P < .01).
      Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with
      chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control
      children. All four controls were underweight (P < .01). Cyclospora was identified
      in specimens from one adult and one child with acute diarrhea (HIV-). Thus,
      Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen
      identified. Cryptosporidium and Enterocytozoon were associated with malnutrition.
      Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children
      has not been described previously.

PMID- 10064251
TI  - Survival and prognostic factors of invasive aspergillosis after allogeneic bone
      marrow transplantation.
AB  - To determine prognostic factors for survival in bone marrow transplant recipients
      with invasive aspergillosis (IA), we retrospectively reviewed 27 IA cases
      observed in our bone marrow transplantation unit between January 1994 and October
      1994. On 30 September 1997, six patients were alive and disease-free. The median
      survival after IA diagnosis was 36 days. Of eight variables found to be related
      to survival according to the univariate analysis, graft-versus-host disease
      (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose
      taken during the week preceding IA diagnosis (CPDlw) (P < .0001) were selected by
      a backward stepwise Cox regression model. A three-stage classification was
      established: CPD1w of < or =7 mg/kg (3 of 8 patients died; 60-day survival rate,
      88%), CPD1w of >7 mg/kg and no GVHD (9 of 10 patients died; 60-day survival rate,
      20%), and CPD1w of >7 mg/kg and active acute grade 2 or more or extensive chronic
      GVHD (9 of 9 patients died; 30-day survival rate, 0) (P < .0001).

PMID- 10064252
TI  - Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic
      cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The
      Canadian Fluconazole Prophylaxis Study Group.
AB  - A randomized, double-blind trial comparing oral fluconazole (400 mg daily) with
      placebo as prophylaxis for adult patients receiving intensive cytotoxic therapy
      for acute leukemia or autologous bone marrow transplantation was conducted in 14
      Canadian university-affiliated hospitals. Although fluconazole prophylaxis did
      not obviate the need for parenteral antifungal therapy compared with placebo (81
      [57%] of 141 vs. 67 [50%] of 133, respectively), its use resulted in fewer
      superficial fungal infections (10 [7%] of 141 vs. 23 [18%] of 131, respectively;
      P = .02) and fewer definite and probable invasive fungal infections (9 vs. 32,
      respectively; P = .0001). Fluconazole recipients had fewer deaths attributable to
      definite invasive fungal infection (1 of 15 vs. 6 of 15, respectively; P = .04)
      and achieved more frequent success without fungal colonization (52 [37%] of 141
      vs. 27 [20%] of 133, respectively; P = .004; relative risk reduction, 85%) than
      did placebo recipients. Patients benefiting the most from fluconazole prophylaxis
      included those with acute myeloid leukemia who were undergoing induction therapy
      with cytarabine plus anthracycline-based regimens and those receiving marrow
      autografts not supported with hematopoietic growth factors. Fluconazole
      prophylaxis reduces the incidence of superficial fungal infection and invasive
      fungal infection and fungal infection-related mortality among patients who are
      receiving intensive cytotoxic chemotherapy for remission induction.

PMID- 10064253
TI  - Human immunodeficiency virus-associated fever of unknown origin: a study of 70
      patients in the United States and review.
AB  - To characterize the clinical features of human immunodeficiency virus (HIV)
      associated fever of unknown origin (FUO) in the United States, we performed a
      retrospective analysis of cases that fulfilled specific criteria (published by
      Durack and Street in 1991) at two medical centers in the United States between
      1992 and 1997. Seventy cases met criteria for HIV-associated FUO; the mean CD4
      cell count was 58/mm3, and the mean duration of fever was 42 days. A cause of FUO
      was found in 56 of the 70 cases; 43 were of a single etiology, and in 13 cases
      multiple conditions were established. The most common diagnoses were disseminated
      Mycobacterium avium infection (DMAC; 31%), Pneumocystis carinii pneumonia (13%),
      cytomegalovirus infection (11%), disseminated histoplasmosis (7%), and lymphoma
      (7%). In this United States series, FUO occurs most often in the late stage of
      HIV infection, individual cases often have multiple etiologies, and DMAC is the
      most common diagnosis.

PMID- 10064254
TI  - Correlation of periurethral bacterial flora with bacteriuria and urinary tract
      infection in children with neurogenic bladder receiving intermittent
      catheterization.
AB  - Periurethral bacteria are inoculated daily into the urine of children with
      neurogenic bladder during clean intermittent catheterization (CIC). We examined
      how frequently periurethral bacterial species produced bacteriuria in children
      followed longitudinally. When Escherichia coli was detected on the periurethra,
      bacteriuria was also present 93% of the time. When Klebsiella, Pseudomonas, or
      Enterococcus species or nonpathogens were detected on the periurethra,
      bacteriuria was present 80%, 40%, 40%, and 25% of the time, respectively. Clonal
      typing of multiple colonies of E. coli from each periurethral and urine culture
      revealed that children carried only one or two E. coli clones in their urinary
      tracts over months of surveillance. When E. coli was detected in the urine, the
      identical clone was on the periurethra. E. coli persisted for weeks in the urine
      without causing symptoms. Occasionally the same E. coli clone carried for weeks
      caused a urinary tract infection. Bacteriuria frequently occurs after inoculation
      of periurethral E. coli into the urine during CIC.

PMID- 10064255
TI  - Fluoroquinolone toxicity profiles: a review focusing on newer agents.
AB  - For 2 decades fluoroquinolones have been found to be generally well-tolerated and
      safe. Adverse events may be inherent to the class or influenced by structural
      modifications. The commonest adverse events are gastrointestinal tract (GI) and
      central nervous system (CNS) reactions; nephrotoxicity and tendinitis are
      infrequent, but agents differ greatly in phototoxic potential. Fluoroquinolones
      are safe in elderly, human immunodeficiency virus-infected, and neutropenic
      patients, but because of possible effects on articular cartilage, they are not
      currently recommended for children or pregnant women. Four new agents have
      recently been licensed. Levofloxacin causes few GI or CNS adverse events and is
      minimally phototoxic. Sparfloxacin infrequently causes GI or CNS effects but is
      associated with relatively high rates of phototoxicity and prolongation of the
      electrocardiographic QTc interval (Q-T interval, corrected for heart rate).
      Grepafloxacin causes relatively high rates of GI effects, taste perversion, and
      QTc interval prolongation, but it is minimally phototoxic. Trovafloxacin is
      associated with a moderate rate of GI effects and a relatively high incidence of
      dizziness but has low phototoxic potential.

PMID- 10064256
TI  - Occupational human immunodeficiency virus infection in health care workers:
      worldwide cases through September 1997.
AB  - The average estimated risk of human immunodeficiency virus (HIV) infection for
      health care workers following a percutaneous or mucous exposure is <0.5% in
      incidence studies, although a case-control study suggests it is much higher for
      highest-risk percutaneous exposure. To characterize exposures resulting in HIV
      transmission, we reviewed available data on occupational cases reported
      worldwide, identifying 94 documented and 170 possible cases. The majority of
      documented infections occurred in nurses, after contact with the blood of a
      patient with AIDS by means of percutaneous exposure, with a device placed in an
      artery or vein. High-exposure job categories, e.g., midwives and surgeons, are
      represented mostly among possible cases. Transmission occurred also through
      splashes, cuts, and skin contaminations, and in some cases despite postexposure
      prophylaxis with zidovudine. Health care workers could benefit if these data were
      incorporated in educational programs designed to prevent occupational bloodborne
      infections.

PMID- 10064257
TI  - The role of Citrobacter in clinical disease of children: review.
AB  - Various species of Citrobacter may cause infections in neonates and
      immunocompromised hosts. Citrobacter koseri (formerly Citrobacter diversus) is
      best known as the cause of sepsis and meningitis leading to central nervous
      system (CNS) abscesses in neonates and young infants. Early onset and late-onset
      infections occur as for other neonatal bacterial infections. The majority of
      cases are sporadic, with no clear source of infection. A few have been confirmed
      to be vertically transmitted, and nosocomial outbreaks have occurred in neonatal
      care units. The pathophysiology is not well understood, but a surface protein has
      been identified as a possible virulence factor among strains that cause
      citrobacter brain abscesses in neonates. Despite improvements in diagnostic
      imaging techniques, surgery, and antibiotic therapy, approximately one-third of
      infants with abscesses die, and one-half sustain CNS damage. In this article, the
      taxonomy, epidemiology, pathogenesis, diagnosis, treatment, and outcome of
      citrobacter disease in children are reviewed.

PMID- 10064258
TI  - A World Wide Web selected bibliography for pediatric infectious diseases.
AB  - A pediatric infectious diseases bibliography of selected medical reference
      citations has been developed and placed on the World Wide Web (WWW) at
      http://www.pedid.uthscsa.edu. A regularly updated bibliography of >2,500 selected
      literature citations representing general reviews and key articles has been
      organized under a standard outline for individual infectious diseases and related
      topics that cover the breadth of pediatric infectious diseases. Citations are
      categorized by infectious disease or clinical syndrome, and access can be
      achieved by the disease or by syndrome or the name of the pathogen. Abstracts,
      and in some cases the complete text of articles, may be viewed by use of
      hypertext links. The bibliography provides medical students, residents, fellows,
      and clinicians with a constantly available resource of current literature
      citations in pediatric infectious diseases. The WWW is an emerging educational
      and clinical resource for the practice of clinical infectious diseases.

PMID- 10064259
TI  - Cerebral venous thrombosis: a new manifestation of neurobrucellosis.

PMID- 10064260
TI  - Abdominal lymphadenopathy in malaria.

PMID- 10064261
TI  - EMERGEncy ID NET: an emergency department-based emerging infections sentinel
      network.

PMID- 10064262
TI  - Plasma and cerebrospinal fluid saquinavir concentrations in patients receiving
      combination antiretroviral therapy.

PMID- 10064263
TI  - Pacemaker endocarditis due to Staphylococcus lugdunensis: report of two cases.

PMID- 10064264
TI  - Comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for
      febrile granulocytopenic patients.

PMID- 10064265
TI  - Refractory mucosal candidiasis in patients with human immunodeficiency virus
      infection.

PMID- 10064266
TI  - Gamma knife radiosurgery in cerebral echinococcosis.

PMID- 10064267
TI  - Combination antibiotic therapy for severe melioidosis.

PMID- 10064268
TI  - Community-acquired pneumonia in human immunodeficiency virus-infected patients.

PMID- 10064269
TI  - Varicella-Zoster virus infection associated with acute liver failure.

PMID- 10064270
TI  - Platelet membrane early activation markers during prolonged storage.
AB  - The relationship between platelet aging and early markers of membrane activation
      have not been defined clearly. Activation markers expressed during prolonged
      storage are similar if not identical to those that appear after exposure to
      thrombin. Using flow cytometry, we investigated platelet membrane expression of
      CD62P, CD63, and annexin V binding (i.e., loss of membrane asymmetry) in
      platelets stored for up to 11 days under standard blood banking conditions. We
      compared five apheresis platelets to two random donor platelet concentrates, and
      to one pooled platelet preparation from six single platelet concentrates before
      and after exposure to thrombin. CD62P, CD63 expression, and annexin V binding
      increased during storage albeit with different kinetics. The differential
      increments observed between resting and thrombin (1 unit/ml) activated platelets
      showed an inverse correlation to storage time for CD62P, CD63, and annexin V
      binding, which was identical to published survival curves. A difference between
      apheresis platelets and platelet concentrates was observed only on day 1. Our
      data indicate that the in vitro platelet reserve activity to thrombin activation
      mirrors that of radiolabeled platelet survival in vivo and that platelet cross
      sectional residual life span can explain their diminished capacity to respond to
      thrombin as a function of viability.

PMID- 10064271
TI  - Contact activation factors in plasma from women on estrogen replacement therapy
      after ovariohysterectomy.
AB  - The plasma levels of factor XII, prekallikrein, factor XI, and high molecular
      weight kininogen were studied in women with bilateral oophorectomy and
      hysterectomy who received hormone replacement therapy with a 2 mg daily dose of
      estradiol valerate. Also plasminogen activator activity was investigated. The
      observations made provide support for the assumption that the low doses of
      estrogen used in hormone replacement therapy do not significantly affect the
      levels of contact activation or fibrinolytic factors in plasma. Plasma obtained
      from young, healthy women was used as a standard reference material.
      Significantly higher levels of factor XII and prekallikrein were registered in
      functional tests in the ectomized women than in the reference material, an
      increase not observed in the immunological assays. These observations are
      discussed in light of recently published data from our laboratory on an increase
      in the measured level of factor XII obtained upon the removal of IgG before
      assay. Also a marked increase in urokinase activity was registered in the
      ectomized women. The high levels of factor XII, prekallikrein, and urokinase, as
      compared with the reference material, seemed to be age dependent, being also
      observed in a group of naturally postmenopausal women.

PMID- 10064272
TI  - Insertion of the Asp-Ser/Phe sequence in the P' position of hirutonin provides
      molecules having both antithrombin and disintegrin activity.
AB  - We have developed novel synthetic peptides that display both antithrombin and
      disintegrin activity. These peptides were derived from hirutonins, a class of
      potent proteolytically resistant thrombin inhibitors, in which a dipeptidyl
      sequence, Asp-Phe or Asp-Ser, was introduced after the proteolytically resistant
      ketomethylene arginyl glycine isostere. These modified hirutonins inhibited the
      amidolytic activity of alpha-thrombin (Ki approximately 35 nM), prevented
      fibrinogen clotting (dTT approximately 100 nM) and inhibited human platelet
      aggregation and 5-hydroxytryptamine secretion induced by alpha-thrombin (IC50
      approximately 600 nM). Unlike their parent hirutonins, they inhibited SFLLR-NH2
      induced human platelet aggregation (IC50 approximately 45 microM) without
      inhibition of 5-HT secretion. These peptides also competed for fibrinogen binding
      to purified GpIIbIIIa integrin (IC50 approximately microM) and prevented
      attachment of B16-F10 mouse melanoma cells to vitronectin. We conclude that
      addition of the dipeptidyl sequence, Asp-Phe or Asp-Ser, in hirutonin molecules
      confers disintegrin activity. However, this activity was not superior to the
      activity observed with the linear RGDS peptide and was achieved at the expense of
      direct antithrombin activity. Additional modifications around the RGD-like
      adhesion sequence may permit identification of the appropriate conformation for
      optimal binding to thrombin and to specific integrin receptors.

PMID- 10064273
TI  - Effects of antithrombin and protein C on thrombin generation in newborn and adult
      plasma.
AB  - It has been suggested that antithrombin (AT) and protein C (PC) might be less
      important in newborn plasma than in adult plasma for the inhibition of clotting
      activation. To assess the importance of AT and PC for the regulation of thrombin
      generation in newborn as compared with adult plasma, thrombin generation was
      determined in the presence of different concentrations of AT and PC. In both,
      newborn and adult plasmas, reduction of AT and PC resulted in an increase of
      thrombin generation after intrinsic activation. On the other hand,
      supplementation of AT and PC decreased thrombin generation in a dose-dependent
      manner. Clotting times were influenced by different PC concentrations, whereas
      clotting times were almost not affected by different amounts of AT. Our study
      suggests that the significance of AT and PC in the regulation of thrombin
      generation is the same in newborn and adult plasma. Our experimental results also
      support the notion that administration of AT or protein C concentrates may be
      beneficial in some clinical situations leading to an increased clotting
      activation in newborns.

PMID- 10064274
TI  - Imaging thromboembolism with Tc-99m-labeled thrombospondin receptor analogs TP
      1201 and TP-1300.

PMID- 10064275
TI  - Reflective, cheering and challenging thoughts about nursing for the next
      millennium.

PMID- 10064276
TI  - Mildmay AIDS Centre, Uganda.

PMID- 10064277
TI  - Nurse practitioners and the problem of discounting.
AB  - Nurse practitioners (NPs) are key primary care providers in health care reform.
      The purpose of this paper is to discuss discounting, a social problem for NPs
      discovered in this grounded theory study. Discounting refers to behaviours
      directed towards NPs that they perceived as degrading. Data collection included
      open-ended, in-depth interviews on the nature of NP practice with 23 NPs, and 10
      key members representing the Florida State Board of Nursing, Florida Nurses
      Association, American Nurses Association, and National Council of State Boards of
      Nursing. Excerpts that illuminated discounting were obtained from field notes
      about organizational documents, state legislative committee hearings, and
      professional NP association meetings. Data analysis using the grounded theory
      method revealed that NPs in this study struggled to establish their roles from a
      position of marginality in a context of conflict and negativity. NPs were
      subjected to social psychological and social structural discounting. This
      research serves to raise the consciousness of NPs with the hope that such
      awareness will facilitate personal and group action to combat discounting in
      their daily work and at local, state and national levels.

PMID- 10064278
TI  - Shift work and its impact upon nurse performance: current knowledge and research
      issues.
AB  - Previous research investigating shift work and its impact upon the quality of
      registered nurse performance and outcomes (including biological, psychosocial and
      organizational) is reviewed. The present study, which involved non-participant
      observation of staff nurses (n = 34) within their first year of practice (Part 1
      or Part 12 of the United Kingdom Professional Register), is described. The
      findings demonstrated support for earlier research which suggested that 12 1/2
      hour shifts are associated with less effective performance. This study, together
      with previous research, highlights important indicators for the design and
      management of future empirical work which is required to investigate the
      influence of shift work upon process as well as outcomes for nurses, service
      users and the employing organization. This is particularly pertinent in the light
      of recent changes in work patterns. The well-being and effectiveness of the
      nursing workforce requires enhancement, and the effective management of shift
      work is a key strategy in achieving this.

PMID- 10064279
TI  - Health beliefs and their influence on United Kingdom nurses' health-related
      behaviours.
AB  - BACKGROUND: Because there is a demonstrated empirical link between nurses'
      personal health habits and their tendency to raise health issues with clients,
      researchers suggest that nurses can improve their health promotion role if they
      adopt health-related behaviours. Few researchers, however, have identified the
      factors that influence nurses' health-related behaviours. AIMS: To describe
      nurses' beliefs about the importance of health-related behaviours, and
      investigate the relationship between these beliefs and their health-related
      behaviours. DESIGN: A cross-sectional survey from which nested-case control
      comparisons were made. SAMPLE: One hundred and thirteen nurses attending tertiary
      level education courses in London and Essex. MEASURES: Health Behaviour Survey
      and a scale measuring nurses' beliefs about the importance of health-related
      behaviours. RESULTS: Nurses' health beliefs significantly influenced the practice
      of 14 health-related behaviours. CONCLUSIONS: The findings from this study
      support the view that nurses' practice of many behaviours linked to health and
      longevity are influenced significantly by their beliefs about the importance of
      these behaviours. Changing nurses' beliefs about the importance of health-related
      behaviours through specific health promotion sessions are meaningful as they may
      improve nurses' health promotion role.

PMID- 10064280
TI  - A comparative study of the perceptions of British mental health nurses and
      psychiatrists of their work environment.
AB  - This comparative study of the perceptions of mental health nurses and
      psychiatrists about aspects of their work environment was undertaken in the West
      Midlands in England. The aim of the study was to ascertain the extent to which
      the environment in which mental health professionals' work impacts on their own
      mental and physical well-being. Seventy-four psychiatrists and 301 mental health
      nurses responded to a postal questionnaire. Analysis of data indicated that
      significant differences exist between nurses and psychiatrists in their working
      conditions, their physical working environment, their sources of support with a
      work-related problem, and the effects of their work on their own mental and
      physical health. The main recommendation derived from this study was to improve
      communication between mental health professionals and their managers by giving
      more structured feedback and guidance about one's work performance. This may help
      to alleviate the mental strain many mental health professionals experience in
      their work.

PMID- 10064281
TI  - Evaluating clinical outcome and staff morale in a rehabilitation team for people
      with serious mental health problems.
AB  - Tameside and Glossop rehabilitation team (in England) have developed a
      progressive and targeted service for people with serious mental health problems
      through the systematic implementation of research-based evidence in practice and
      service configuration. This study was undertaken to provide a method of auditing
      the clinical outcome of the service and monitoring staff morale in a manner which
      could be integrated in the day to day delivery of services, and which could
      inform future service developments. Changes in the functioning of the total
      population of rehabilitation team clients were assessed over a 1-year period by
      Health of the Nation Outcome Scales (HoNOS) ratings at 6-monthly intervals.
      Factors causing stress and stress levels among all staff were assessed using the
      Mental Health Stress Questionnaire. The findings give clear indications of areas
      of the service which needed improving or changing, and identify ways in which the
      ongoing process of data collection might be refined.

PMID- 10064282
TI  - Nursing acute psychiatric patients: a quantitative and qualitative study.
AB  - Political and managerial attention has focused on the consequences of the failure
      of community services to provide effective care to a small number of people with
      severe mental illness. However, the nature and value of care in hospitals have
      received less scrutiny. This paper addresses deficiencies in our knowledge about
      nursing care in acute psychiatric wards. It reports the findings from a recently
      completed study for the United Kingdom Department of Health. Four key
      developments are identified which, together, pose significant problems for
      nursing in acute wards: the increasingly diverse patient mix in wards; the volume
      of administrative duties performed by nurses; the weakness of multidisciplinary
      team working; and inappropriate education. In conclusion, the challenges for
      managers and clinicians responsible for local policy and practice and, by
      extension, those at the centre responsible for such services, are examined.

PMID- 10064283
TI  - Patient initiatives during the assessment and planning of psychiatric nursing in
      a hospital environment.
AB  - The qualitative study reported in this paper aims to describe the planning and
      assessment of psychiatric nursing in a hospital environment. The theoretical
      framework consists of the three types of psychiatric nursing outlined in a
      developmental model of nursing: confirmatory, educational and catalytic.
      Confirmatory psychiatric nursing is based on a hierarchical and authoritarian
      model. Educational psychiatric nursing is based on a professionally driven and
      behavioural model. Catalytic psychiatric nursing is systematic, theoretical, and
      research-based. Catalytic psychiatric nursing may vary, depending on the
      patient's needs, from confirmatory and educational to situationally determined
      nursing. However, it always enables patient initiatives. The purpose of this
      paper is to describe patient initiatives during the assessment and planning of
      patient care by an interdisciplinary mental health team in a psychiatric hospital
      environment, and the assessment and planning as described by nurses working in a
      hospital environment. The data, which were collected in two psychiatric hospitals
      by videotaping interdisciplinary teamwork situations and recording interviews of
      nurses afterwards, consisted of 384 pages of written text. A total of 640
      sentences were identified in the text as reflecting the assessment of care by the
      interdisciplinary team and by the nurses working in the hospital environment.
      Deductive content analysis techniques were used to analyse the written data. The
      results showed that nursing was described by the nurses to be catalytic in 13% of
      the cases, while the same nurses assessed psychiatric nursing to be most commonly
      educational (40%) or confirmatory (47%).

PMID- 10064284
TI  - The development of evidence-based nursing.
AB  - This paper argues that the current conception of evidence-based medicine has its
      limitations in the promotion of research which effects the quality of service in
      any health care system. It also poses something of a difficulty for the
      development of evidence-based nursing in particular. This paper advocates the
      more broad based concept of evidence-based practice and discusses its potential
      for addressing theory/practice problems and the uptake of nursing research. The
      broader conceptualization of evidence-based practice focuses on the integration
      of available evidence and the tacit knowledge of the investigator. An evidence
      based practice project undertaken in Hong Kong is outlined as this provided the
      basis of many of the conclusions made in this paper. Three vignettes are given in
      order to demonstrate the nature of the evidence-based practice projects which
      have been conducted. The critical elements of evidence-based practice projects
      are outlined. Finally issues concerning the process of generating evidence, the
      relationship to continuous quality improvement and the cost effectiveness of
      evidence-based practice are discussed in more detail.

PMID- 10064285
TI  - Individualized care: is it possible to plan and carry out?
AB  - The purpose of the study reported in this paper was to assess the reality of
      attempting to deliver individualized nursing care. An ethnographic case study
      research design was used on a nursing development ward. The organizational
      framework was a mixture of primary nursing and team nursing. Activities of three
      patients were observed over 4 days each, covering 16 hours of the 24-hour period
      for each patient. The observations were unstructured, but attempted to relate
      activities to the nursing care plan. Informal, semi-structured, tape-recorded
      interviews were undertaken with 12 of the ward staff, qualified and unqualified.
      The interviews asked questions relating to aspects of planning care, delivering
      care and ensuring continuity of care. In addition, two nurses kept diaries of
      significant events for 5 days. Field notes of observations were coded for
      analysis, interviews were transcribed and coded and diaries were coded. The
      findings suggest that whereas the patient is offered choice on some occasions, at
      other times the patients fit into the routine. Supervision of meals and the use
      of the care plan were issues raised. Communication between nurses was reported to
      be well-developed and helped to ensure continuity of care. Difficulties in
      delivering individualized care were related to issues of skill mix and lack of
      support staff.

PMID- 10064286
TI  - The effects of primary nursing on work-related factors.
AB  - This study investigates the effects of a primary nursing care delivery system on
      some work-related factors of nurses in long-stay psychiatric care settings. In a
      quasi-experimental research design a cohort of 176 nurses was followed for 2.5
      years. Results showed that as a result of primary nursing the primary nurses
      found more autonomy in their work and experienced it to be less complex.
      Furthermore, primary nurses performed personal care tasks less frequently and
      worked more according to a patient-oriented care model. Several additional
      analyses were performed owing to the two main problems encountered in this study,
      namely a high dropout due to job turnover among nurses and the imitation of the
      intervention by the control group.

PMID- 10064287
TI  - Towards (re)conciliation: (re)constructing relationships between indigenous
      health workers and nurses.
AB  - Currently in Australia, both Aboriginal and non-Aboriginal Australians are
      attempting to reconcile themselves with a history of colonization/invasion, which
      resulted in human rights violations against Australia's indigenous people.
      Australian nursing has to examine its past in relation to the treatment of
      Aboriginal Australians. Relationships between nurses and Aboriginal health
      workers are the most commonly occurring professional relationships between nurses
      and Aboriginal people and are of key importance to the successful delivery of
      health services to Aboriginal communities. This qualitative study, grounded in
      feminism, aimed to explore the professional relationships between Aboriginal
      health workers and nurses and to develop insights which could assist the
      Australian nursing profession through a process of reconciliation with Aboriginal
      Australians. Feminist analysis of narrative text revealed several key themes as
      being crucial to this process. These were: learning to know and understand;
      towards workplace equity; and skill sharing -- learning from each other.
      Implications for nursing, in its journey toward reconciliation with Aboriginal
      Australians, are drawn from this study.

PMID- 10064288
TI  - Protective steering: a grounded theory study of the processes by which midwives
      facilitate informed choices during pregnancy.
AB  - Helping women to make informed choices during pregnancy is an important and
      complex part of a midwife's role that does not appear as yet to have been
      investigated in depth. The purpose of this study was to use a grounded theory
      approach to investigate the processes involved when midwives engage in
      facilitating the making of informed choices for women in the United Kingdom.
      Interactions between midwives and pregnant women were observed and recorded and
      focused interviews were conducted with the midwives. Data were analysed according
      to the grounded theory method. The core category was identified as protective
      steering, whereby midwives were concerned to protect the women in their care, as
      well as themselves, when choices were made. Substantive categories were
      orienting, protective gatekeeping and raising awareness.

PMID- 10064289
TI  - Factors related to successful breast feeding by first-time mothers when the child
      is 3 months old.
AB  - The aim of the reported study was to gain information on those factors which
      contribute to the success of breast feeding in first-time mothers when the child
      is 3 months old. The study is part of a wider longitudinal project which follows
      up the growth to motherhood of first-time mothers in Finland over a period of 8
      months postpartum. Data collection was by questionnaires distributed between
      March and September 1995. The sample comprised 271 first-time mothers. The
      mothers completed the questionnaires when their infants were 3 months old. The
      analysis applied was a polychotomic logistic regression analysis. When the child
      was 3 months old those mothers who perceived themselves competent as mothers and
      who felt that society appreciated motherhood appropriately coped better with
      breast feeding. Also, those mothers who had worked at home prior to the birth of
      the child and who felt that breast feeding was important in motherhood coped
      better with breast feeding. Those mothers whose state of mind was more balanced
      after the birth coped better with breast feeding. The more affirmation the mother
      received from members of her social network the better she coped with breast
      feeding. The research findings suggest that factors influencing successful breast
      feeding in first-time mothers at 3 months postpartum are the mother's own
      resources and attitude to breast feeding, support from the social network and the
      current appreciation of breast feeding in society.

PMID- 10064290
TI  - Health visiting as therapy: a phenomenological perspective.
AB  - In the course of their work British health visitors encounter many individuals
      and families with problems. Support is usually offered, but if that support is
      for psychological health needs, it is less likely to be accepted as legitimate
      health visiting practice. Where a referral is either not accepted, or placed on a
      waiting list, the health visitor will support the client through a holding
      relationship until the other appropriate professionals can accept the referral.
      From a literature review, helping styles and holding relationships provide a
      'listening to' opportunity, a 'being there for' and an exploration of the
      presenting problems. This paper aims to explore the practice of health visiting
      as therapy and urges health visitors to expand their psychological support of
      clients in preference to other role developments.

PMID- 10064291
TI  - A telephone intervention to reduce fatigue and symptom distress in mothers with
      difficult infants in the community.
AB  - The purpose of this study was to test the effectiveness of a telephone
      intervention to reduce fatigue and the resulting symptom distress of mothers in
      Iceland who reported having a behaviourally difficult infant of 2-3 months of
      age. A sample of 78 mothers who reached distress criteria of depressive symptoms
      and parental stress was selected and randomly allocated in a controlled
      experimental study. In a brief intervention both maternal distress and infant
      difficulty were discussed. Results indicate a significant (P < 0.001)
      intervention effect on fatigue and its side-effects. It is concluded that
      intervention by telephone can be effective with fatigued mothers caring for a
      difficult infant.

PMID- 10064292
TI  - Coping strategies used by hospitalized stroke patients: implications for
      continuity and management of care.
AB  - This paper describes findings from an English study into the perceptions of multi
      professional practice given by stroke patients, their informal carers and
      hospital staff. Unstructured interviews were conducted with nine stroke patients
      and eight informal carers. Case studies were developed from the interview data
      which formed the basis of a questionnaire designed to ascertain the aims of care
      for the case studies and the location of professional responsibility for meeting
      these aims. This was returned by 31 respondents from a range of professional
      backgrounds. The findings indicate that patients and carers sought out
      relationships with staff and other patients in order to gain information to help
      them understand their uncertain futures. Professional staff were reluctant to
      pass specific information on to patients as it might be misleading in each
      individual case. The uncertainty surrounding individual recovery means that
      supportive relationships initiated by patients and carers may need to be
      recognized and nurtured.

PMID- 10064293
TI  - Use of initial risk assessment and recording as the main nursing intervention in
      identifying risk of falls.
AB  - The consequences of falls among hospital patients are a great problem, for the
      patient, the family and society, and cost billions of dollars. In Sweden, almost
      one-third of all hip fractures occur in the hospital population. Despite this,
      very few prevention strategies have been developed and tested. In this study, a
      risk assessment and recording programme in relation to the risk of falling among
      patients in a geriatric department at a Swedish hospital was implemented. The
      records of all patients admitted to a geriatric unit during one year, and a
      stratified random sample of patient records, constituting the control group from
      the year before, were reviewed. No recording of assessments regarding the
      patients' risk of falling, and no preventive nursing interventions, were found in
      the records of the control group. The study group, however, increased the
      recording of risk assessment to 96%. Only implemented nursing interventions were
      found in the patients' records, despite the fact that Swedish law makes it
      obligatory for the registered nurse to record both the planning and
      implementation of nursing care. In the study group there were explicit
      descriptions of problems of concern for nursing regarding the patients' risk of
      falling in less than one-third of the records, the nursing care plans were rare,
      and the evaluations were not satisfactory. Nursing interventions consisted mostly
      of information or education, promotion of patient participation, and structuring
      of the environment. There was no agreement on any standard-care plan. Recording
      of falls was found more often in the study group than in the control group
      (probably due to more careful recording), but the proportion of injuries in
      relation to falls was higher in the control group. The results of this study may
      be used as a baseline for developing a nursing strategy and documentation
      relating to falls.

PMID- 10064294
TI  - Use of physical restraints on elderly patients: an exploratory study of the
      perceptions of nurses in Hong Kong.
AB  - A qualitative study was designed to explore nurses' perceptions of the use of
      physical restraints on elderly patients in Hong Kong. Content analysis of semi
      structured interviews with 20 registered nurses working in medical and geriatric
      settings of two regional hospitals revealed that although nurses generally had
      mixed feelings about the use of physical restraints on elderly patients, they did
      not question this 'routine' practice and their knowledge about the consequences
      and alternatives to the use of restraint was limited. It was found that nurses
      had an overriding concern in ensuring elderly patients' physical safety and using
      restraints therefore provided them with a sense of security. The deleterious
      impact of restraint on the care received by elderly patients was largely
      unrecognized. Implications for practice and future studies are discussed in the
      light of these findings.

PMID- 10064295
TI  - Nursing care of older people: a personal construct theory perspective.
AB  - This paper outlines the use of the repertory grid technique, with nurses caring
      for elderly residents, and residents of a nursing home. The method focuses on the
      individuality of each person's attempt at making sense of her/his caring world.
      Previous papers have focused on a discussion of the repertory grid technique as a
      research method and tool for psychiatric nurses, an overview of studies using
      this technique with nurses and social workers, and applications of personal
      construct theory (from which the technique is derived) to nursing research. A
      paper by Rawlinson described content analysis of the role constructs elicited
      from the nurses. In this study, content analysis of caring constructs elicited by
      nurses and residents was also undertaken, and the results are presented.
      Additionally, principal component analysis of the repertory grids was carried
      out, and three examples are presented. This combined analysis provides an in
      depth insight into nurses' perceptions of caring for others; perceptions which
      guide their caring behaviours. This information can be used by individual nurses
      to review their caring practice.

PMID- 10064296
TI  - The contribution of nursing to cancer prevention.
AB  - Cancer is a major killer of modern man, yet despite recent advances in knowledge
      of cancer and its causes, prevention remains a significant challenge within
      healthcare. Theories of health promotion give an insight into the perspectives on
      disease prevention whilst frameworks for disease prevention can be useful in
      helping identify and address the difficulties inherent in preventing this deadly
      disease. Within this paper Caplan's framework forms the basis for discussion of
      the issues related to cancer prevention in the United Kingdom as part of
      nursing's health promotion role. It is suggested that a 'chain of prevention'
      would ideally exist linking the laboratory scientists researching cancer and the
      general public. 'Weak links' are identified prior to suggestions for remedial
      strategies.

PMID- 10064297
TI  - Dimensions of health-related quality of life in persons living with HIV disease.
AB  - The purpose of this secondary analysis was to test empirically the influence of
      biological and physiological variables, symptom status, functional status,
      general health perceptions, characteristics of the individual and characteristics
      of the environment on overall quality of life in persons living with HIV disease.
      Path analysis, using multiple linear regression, was used to examine the fit
      between a health-related quality of life (HRQOL) theoretical model and data from
      a sample of 142 persons with an AIDS diagnosis. Thirty-two per cent of the
      variance in overall quality of life was explained by the HRQOL model with symptom
      status having the greatest influence (beta = -0.237, R2(Y x 2) = 5%). This
      analysis suggests that symptom status, functional status and general health
      perceptions are key dimensions of HRQOL. With a focus on prevention, health
      promotion, symptom management, and the alleviation of acute and chronic illness
      effects, HRQOL may be appropriate for capturing the outcomes of nursing
      interventions.

PMID- 10064298
TI  - Evidence-based practice. A philosophical and political analysis: some matters for
      consideration by professional practitioners.
AB  - This paper evaluates the concept of evidence-based practice (EBP) and appraises
      critically the implementation process of the EBP initiative, noting its
      consonance with the aspirations of the dominant political culture and offering a
      critique of the inherent contradictions and ethical dilemmas associated with it.
      A critical evaluation of the implications for practitioners and service users is
      offered and the authors argue that while the concept of EBP is a laudable one,
      there is a need to exercise caution about uncritical acceptance and evidence that
      a more eclectic and less reductionist approach to EBP is essential for quality
      service development.

PMID- 10064299
TI  - Talking on the telephone with people who have experienced pain in hospital:
      clinical audit or research?
AB  - The adequacy of postoperative pain management in British hospitals appears
      insufficient to improve patient care, and much of the research and clinical audit
      in postoperative pain has failed to seek the patient's perspective. This paper
      reports on the findings from a semi-structured telephone interview survey which
      formed part of a hospital-wide audit on postoperative pain at a district general
      hospital in the south of England. Of a total of 360 completed audit
      questionnaires, 114 patients left their telephone number and 29 were interviewed.
      Content analysis revealed five main themes: inadequate information, pain at home,
      staff attitudes, expectations of pain, and ward atmosphere. Several patients
      identified insightful strategies that potentially could improve pain management.
      The telephone interview generated a richness of data that had not been reported
      before in this important area. Some authors view clinical audit and research as
      having different characteristics but this work raises important questions for
      both approaches when using the semi-structured telephone interview. The ethical
      issues pertaining to collection of audit data using the telephone interview are
      discussed.

PMID- 10064300
TI  - Mentorship in nursing: a literature review.
AB  - The recent increase in published work relating to the supervision of nurses and
      in particular mentorship suggests that nurses value the opportunities that such
      schemes present for developing practice. Much of the literature surrounding
      mentorship concerns the supervision of students in practice settings but more
      recently, especially following the changes to post-registration education,
      attention has shifted to the supervision of qualified nurses. Although the
      principles of supervision for students and qualified nurses are the same,
      differences do occur in supervisory practices. This review examines the
      literature associated with the supervision of student nurses and focuses on the
      nature and practice of mentorship in practice settings. The literature reveals
      that confusion exists regarding both the concept of mentorship and the role of
      the mentor. Many authors propose models or frameworks for mentoring activities.
      These tend to outline the stages of the mentoring process and the relationship
      between mentor and mentee. No one model is seen as more appropriate than another
      and choice usually depends upon the mentor's familiarity with a particular
      framework. It is also evident that there is inconsistency in the length and level
      of preparatory courses for mentors. As yet there is in the United Kingdom no
      national minimum requirement or common preparation route and in practice mentors
      are prepared by way of the appropriate National Board Teaching and Assessing
      module and/or short local 2-day course.

PMID- 10064301
TI  - The educational preparation of staff in nursing homes: relationship with resident
      autonomy.
AB  - The following paper reports on a survey of nursing homes in three health regions
      in England which formed part of a wider study to evaluate educational preparation
      for the nursing care of older people. The aims of the survey were to describe the
      educational preparation of staff employed within nursing homes and to explore
      relationships between educational preparation and one indicator of quality of
      care. A self-completion questionnaire was addressed to the senior nurse within a
      random sample of nursing homes. The instrument included a previously validated
      scale to measure resident autonomy. A total of 976 questionnaires were posted and
      676 were returned, a response rate of 69%. The survey revealed wide variation in
      the educational preparation of staff in nursing homes and in the degree of
      contact with local centres providing nurse education. Statistically significant
      associations were found between resident autonomy and a composite measure of
      educational preparation, the proportion of qualified staff undertaking continuing
      professional education and the degree of contact with educational centres. The
      findings have implications for both purchasers and providers of education in this
      field.

PMID- 10064302
TI  - A descriptive survey to identify the perceived skills and community skill
      requirements of mental health staff.
AB  - Throughout the 1990s mental health care has shifted from a hospital to a
      community-based service. Government policy indicates that staff require further
      education as a result of the shift to community care. However, none of the United
      Kingdom policy documents or mental health literature prescribes what education is
      required. Consequently this multidisciplinary study aimed to identify what
      skills, if any, were required by hospital-based staff to move to a community
      based working environment. Study findings suggest advantages in perceiving skills
      as overlapping and interconnecting. Five common core skills and skill differences
      between professional groups are identified. It is argued that core skills are
      central and common to all groups and specialist skills are those that distinguish
      professional groups one from another and different grades of staff within
      professional groups. While problems of multidisciplinary education are
      considered, nevertheless a case is made for educating staff in core skills within
      a multidisciplinary environment which may be beneficial in achieving community
      care goals.

PMID- 10064303
TI  - A journey to becoming: the student nurse in transition.
AB  - The study reported in this paper explored the nature of the transition
      experienced by student nurses in their journey to becoming qualified nurses. In
      keeping with the developing relationship between the disciplines of anthropology
      and nursing, the methodology of choice was ethnography. Data were collected by
      open-ended questionnaires and interviews with key informants from one English
      College of Nursing undertaking Diploma level Project 2000 Adult Branch Studies.
      Thematic analysis of the data revealed an ill-defined transition for the student
      nurse and this lack of clarity was being perpetuated for many by their dual role
      as both student nurse and worker. This was also creating a potential role
      conflict and a blurring of the boundaries between professional nursing and
      skilled health care work. The data also revealed two 'in limbo' states, a
      ritualized transition phase, and that the rationale for 'learning to become a
      nurse' retains the idealized and vocational imagery of nursing as helping and
      caring for sick people.

PMID- 10064304
TI  - A comparison of pre-Project 2000 and Project 2000 nurses' perceptions of their
      research training, research needs and of their use of research in clinical areas.
AB  - Most of the literature on the research training and education of nurses has
      focused on teaching strategies. Only a few authors have assessed systematically
      the impact of research modules or courses on the knowledge and attitudes of
      nurses. There is a lack of research on nurses' use of research following their
      preparation. This paper reports on some of the data from a large-scale survey of
      the utilization of research among nurses in Northern Ireland. In particular, a
      comparison is made of the perceptions of pre-Project 2000 and Project 2000
      qualified nurses of their research training, research needs, and use of research
      in clinical areas. A questionnaire was distributed to a convenience sample of
      2600 nurses from 23 hospitals in 14 Trusts in Northern Ireland. The response rate
      was 52.6% (n = 1368). The findings show, among others, a shortfall in research
      preparation of pre-Project 2000 nurses in important aspects of research. While
      Project 2000 nurses reported receiving more training, they did not report higher
      rates of research utilization than pre-Project 2000 nurses. Registered mental
      nurses (RMNs) and registered nurses mental handicap (RNMHs) also reported lower
      rates of research utilization than registered general nurses (RGNs), despite
      reporting the same amount of research preparation as RGNs. The implications of
      these findings are discussed.

PMID- 10064305
TI  - The impact of higher education for post-registration nurses on their subsequent
      clinical practice: an exploration of students' views.
AB  - In recent years there has been a large increase in the number of qualified nurses
      in the United Kingdom, who have raised the academic level of their nursing
      qualification to diploma level or above. Correspondingly, there has been little
      research that assesses the value of post-registration education offered by
      universities. In particular, there is a paucity of research regarding the effects
      of courses on the subsequent clinical practice of participants. Studies of post
      registration education appear to be small scale and limited in scope. This paper
      examines the views of diplomates as to the effect of a Diploma in Professional
      Studies in Nursing course on clinical practice. A questionnaire was sent to all
      nurses (n = 169), from the first seven cohorts, who successfully completed the
      course. A response rate of 66.8% (n = 113) was achieved. The respondents reported
      themselves to be more questioning, more able to apply research findings and to
      have a wider knowledge for practice following completion of the course. The
      findings are discussed, limitations of the study addressed and recommendations
      for further research are made.

PMID- 10064306
TI  - Mentoring today--the students' views. An investigative case study of pre
      registration nursing students' experiences and perceptions of mentoring in one
      theory/practice module of the Common Foundation Programme on a Project 2000
      course.
AB  - The study reported in this paper investigated the mentoring experiences and
      perceptions of pre-registration nursing students in one organization, on a
      theory/practice nursing module. It considered the extent to which students'
      understanding and expectations matched their actual experiences. Interviews were
      conducted with 35 students on a Common Foundation Programme, and 15 allocated
      mentors, using a semi-structured interview guide. These were done within the
      clinical setting of the wards on which the students were placed as part of their
      requirements for completion of the module. A distortion of the actual meaning of
      mentoring appears to be present because of the lack of clarity provided, both
      internally by organizations and by the English National Board (ENB) who have
      provided loose guidelines. The implications of this distortion are discussed. The
      application of a mentoring role in practice needs to be re-examined, with the
      provision of a clear structured guide internally and externally, with regard to
      the needs of students and staff who are expected to act as mentors. The study was
      small scale and cannot be generalized. Mentoring, however, is now widely used
      within pre-registration nursing education, even though it is generally considered
      that its use may not be appropriate. Follow-up studies need to be undertaken on
      an ongoing basis, to examine what actually happens in practice, and to consider
      ways of ensuring that the benefits for staff and students are enhanced.

PMID- 10064307
TI  - A fuzzy week for Nurse Der. Rolfian predilections?

PMID- 10064308
TI  - Insights into apolipoprotein B biology from transgenic and gene-targeted mice.
AB  - Over the past five years, several laboratories have used transgenic and gene
      targeted mice to study apolipoprotein (apo) B biology. Genetically modified mice
      have proven useful for investigating the genetic and environmental factors
      affecting atherogenesis, for defining apoB structure/function relationships, for
      understanding the regulation of the apoB gene expression in the intestine, for
      defining the "physiologic rationale" for the existence of the two different forms
      of apoB (apoB48 and apoB100) in mammalian metabolism and for providing
      mechanistic insights into the human apoB deficiency syndrome, familial
      hypobetalipoproteinemia. This review will provide several examples of how
      genetically modified mice have contributed to our understanding of apoB biology,
      including our new discovery that human heart myocytes secrete nascent apoB
      containing lipoproteins.

PMID- 10064309
TI  - Apolipoprotein B in the rough endoplasmic reticulum: translation, translocation
      and the initiation of lipoprotein assembly.
AB  - Apolipoprotein (apo) B and the microsomal triglyceride transfer protein are
      essential for the hepatic assembly and secretion of triglyceride-rich VLDL. To
      understand how apoB initiates the process of lipoprotein formation, interest has
      focused on the biogenesis of its amino terminal globular domain (alpha1 domain).
      When only this domain is expressed in hepatoma cells, no lipoprotein particle
      will form. However, proper folding of the alpha1 domain is essential for the
      internal lipophilic regions of apoB to engage in cotranslational lipid
      recruitment. The essential function of this domain may be related to its capacity
      to promote a specific physical interaction with the microsomal triglyceride
      transfer protein, necessary for apoB's proper folding and lipidation.
      Alternatively, this domain may promote an autonomous lipid recruitment step that
      nucleates microsomal triglyceride transfer protein-dependent lipid sequestration
      by apoB. Forms of apoB that fail to initiate particle assembly or forms
      associated with aberrant underlipidated particles are targeted for intracellular
      turnover. Two sites of apoB degradation have been identified. In hepatocarcinoma
      derived cells, misassembled apoB may undergo progressive reverse translocation
      from the endoplasmic reticulum lumen to the cytosol, a process that is
      mechanistically coupled to polyubiquitination and proteasome-mediated degradation
      on the cytosolic side of the membrane. Alternatively, studies in primary
      hepatocytes reveal that apoB may undergo sorting to a post-endoplasmic reticulum
      compartment for presecretory degradation. In either case, the balance between
      assembly and presecretory degradation of apoB may represent a control point for
      the production of hepatic VLDL.

PMID- 10064310
TI  - Assembly of very low density lipoprotein: a two-step process of apolipoprotein B
      core lipidation.
AB  - The liver plays a primary role in lipid metabolism. Important functions include
      the synthesis and incorporation of hydrophobic lipids, triacylglycerols and
      cholesteryl esters into the core of water-miscible particles called lipoproteins
      and the secretion of these particles into the circulation for transport to
      distant tissues. In this article, we present a brief overview of one aspect of
      the assembly process of very low density lipoproteins, namely, possible
      mechanisms for combining core lipids with apolipoprotein B. This is a complex
      process in which apolipoprotein B interacts with core lipids to form very low
      density lipoproteins by a two-step process that can be dissociated biochemically.

PMID- 10064311
TI  - Estrogen induction of VLDLy assembly in egg-laying hens.
AB  - The yolk of a 60-g chicken egg contains 6 g of triacylglycerols transported to
      the oocyte from the liver of the laying hen in apolipoprotein (apo) B-containing
      particles. With the onset of egg production, estrogen shifts hepatocytic
      lipoprotein production from generic VLDL to VLDLy (yolk targeted). These VLDLy
      are triacylglycerol-rich particles; they are reduced in size by one half, are
      resistant to lipoprotein lipase and are taken up intact by oocyte receptors. The
      VLDLy pathway for apoB provides sufficient energy for the caloric requirements of
      chick development. VLDLy size reduction occurs in spite of surplus liver
      triacylglycerols and is necessary for VLDL particles to pass through the
      granulosa basal lamina and reach the receptors located on the oocyte surface. New
      ultrastructural data show that some proximal tubule cells of bird kidney secrete
      generic VLDL, perhaps providing energy and other VLDL-associated nutrients to
      tissues bypassed by VLDLy. Birds are an apoB100-only species, providing a natural
      in vivo model with which to investigate mechanisms of apoB100 VLDL assembly.
      Preliminary studies of liver lipoprotein assembly intermediates isolated from the
      biosynthetic membranes (endoplasmic reticulum) of the laying hen are consistent
      with the presence of both putative first- and second-step precursor particles of
      VLDLy. These findings suggest that the two-step mechanism of apoB core lipidation
      is an ancient development in apoB biology, handed down to mammals from oviparous
      ancestors.

PMID- 10064312
TI  - The LDL receptor gene family, apolipoprotein B and cholesterol in embryonic
      development.
AB  - In recent years, a number of genes that are involved in cholesterol synthesis,
      its systemic or intercellular transport or lipid metabolism in general have been
      found to play important roles during embryonic development. In this article, we
      present a brief overview of these genes, their molecular functions as we
      understand them to date and our current interpretation of possible mechanisms by
      which genetic deficiency states might affect the development of the embryo, in
      particular the formation of the central nervous system.

PMID- 10064313
TI  - Molecular biology of biotin attachment to proteins.
AB  - Enzymatic attachment of biotin to proteins requires the interaction of a distinct
      domain of the acceptor protein (the "biotin domain") with the enzyme, biotin
      protein ligase, that catalyzes this essential and rare post-translational
      modification. Both biotin domains and biotin protein ligases are very strongly
      conserved throughout biology. This review concerns the protein structures and
      mechanisms involved in the covalent attachment of biotin to proteins.

PMID- 10064314
TI  - Human biotinidase isn't just for recycling biotin.
AB  - For years, the major role of biotin has been as the coenzyme for four
      carboxylases in humans. Although there has been evidence that biotin might have
      other functions, none has been firmly established. The discovery that human serum
      biotinidase has biotinyl-transferase activity, in addition to biotinidase
      hydrolase activity, presents new possibilities for the role of biotinidase in
      biotin metabolism. Specific transfer of biotin to histones by biotinidase
      provides a possible explanation for why biotin is found in the nucleus and the
      nature of its role in the regulation of protein transcription. Future studies
      will help to determine the functions of biotinidase in biotin metabolism and in
      disease states.

PMID- 10064315
TI  - Cellular uptake of biotin: mechanisms and regulation.
AB  - This review describes our knowledge of biotin transport in the small intestine of
      humans and other mammals and presents recent findings in the area. Previous
      studies have shown that biotin transport across the brush border membrane of the
      small intestinal absorptive cells occurs via a carrier-mediated, Na+ gradient
      dependent, electroneutral mechanism. Exit of biotin out of the enterocyte, i.e.,
      transport across the basolateral membrane, also occurs via a carrier-mediated
      process, but the process is Na+ independent and electrogenic. Recent studies from
      our laboratory have shown that the uptake process of biotin in Caco-2 cells, a
      human-derived cultured intestinal epithelial cell line, are under the cellular
      regulation of both a protein kinase C- and a Ca/calmodulin-mediated pathway. In
      addition, the uptake process is shared by another water-soluble vitamin,
      pantothenic acid. For the first time, other recent studies have detected the
      existence of a Na+-dependent, carrier-mediated mechanism for biotin uptake at the
      apical membrane of colonocytes, which could theoretically mediate absorption of
      the biotin synthesized by colonic microflora. This system was again found to be
      shared by pantothenic acid, which is also synthesized by the normal microflora of
      the large intestine.

PMID- 10064316
TI  - Advanced analysis of biotin metabolites in body fluids allows a more accurate
      measurement of biotin bioavailability and metabolism in humans.
AB  - In previous studies, the bioavailability of biotin in humans was estimated from
      the recovery of biotin in urine; urinary biotin was measured by microbial growth
      assays or assays of avidin-binding activity. These assays underestimate
      concentrations of biotin metabolites, which originate from beta-oxidation, sulfur
      oxidation or a combination. We have developed an HPLC/avidin-binding assay that
      is specific for biotin and its metabolites. With the use of the HPLC/avidin
      binding assay, TLC and derivatization with p-dimethylaminocinnamaldehyde, we have
      identified and quantitated biotin and metabolites in urine from six healthy
      adults. Of that total, biotin accounted for 32+/-12%, bisnorbiotin for 52+/-15%,
      bisnorbiotin methyl ketone for 7.9+/-5.8%, biotin-d,l-sulfoxide for 4.0+/-3.2%
      and biotin sulfone for 3.6+/-1.9%. After intravenous administration of 18.4
      micromol of biotin, the urinary excretion of biotin metabolites increased 21-130
      times above baseline values. Because the biliary excretion of biotin is
      quantitatively minor (1.9+/-0.2% of an intravenous [14C]biotin dose in rats),
      intravenously administered biotin is not exposed to intestinal microorganisms.
      Thus we conclude that biotin metabolites in human urine originate from biotin
      catabolism in human tissues rather than biotin catabolism by intestinal
      microorganisms. With the use of the HPLC/avidin-binding assay, we estimated the
      bioavailability of biotin in adults from the urinary excretion of biotin and
      metabolites after ingestion of 2.1, 8.2 and 81.9 micromol of biotin. These data
      provide evidence that biotin is nearly completely absorbed.

PMID- 10064317
TI  - Biotin status: which are valid indicators and how do we know?
AB  - Although estimated average requirements for biotin have been proposed, the human
      requirements for biotin in specific populations and at various ages remain
      uncertain, in part because indicators of biotin status have not been validated.
      With the use of improved methods for measuring biotin and metabolites, a recent
      study indicated that decreased urinary excretion of biotin and bisnorbiotin is an
      early and sensitive indicator of biotin deficiency, but decreased serum
      concentration of biotin is not. Increased urinary excretion of 3
      hydroxyisovaleric acid (3-HIA), a leucine metabolite that is excreted in
      increased quantities with deficiency of the biotin-dependent enzyme beta
      methylcrotonyl-CoA carboxylase, is also an early and sensitive indicator of
      biotin deficiency. When these indicators were assessed longitudinally in 13
      pregnant women, biotin excretion was not significantly decreased early in
      pregnancy but did decrease significantly from early to late pregnancy. Excretion
      of 3-HIA was abnormally increased in about three-fourths of the women studied in
      both early and late pregnancy. Thus, each indicator detected biotin deficiency
      late in pregnancy, but assessment of biotin status for the two indicators
      conflicted early in pregnancy. Preliminary results from a trial assessing
      response of 3-HIA excretion to biotin treatment indicate that biotin status is
      indeed impaired both early and late in pregnancy.

PMID- 10064318
TI  - Symposium: Advances in Measuring Food Insecurity and Hunger in the U.S.
      Introduction.

PMID- 10064319
TI  - Validation of measures of food insecurity and hunger.
AB  - The most recent survey effort to determine the extent of food insecurity and
      hunger in the United States, the Food Security Supplement, included a series of
      questions to assess this complex phenomenon. The primary measure developed from
      this Food Security Supplement was based on measurement concepts, methods and
      items from two previously developed measures. This paper presents the evidence
      available that questionnaire-based measures, in particular the national food
      security measure, provide valid measurement of food insecurity and hunger for
      population and individual uses. The paper discusses basic ideas about measurement
      and criteria for establishing validity of measures and then uses these criteria
      to structure an examination of the research results available to establish the
      validity of food security measures. The results show that the construction of the
      national food security measure is well grounded in our understanding of food
      insecurity and hunger, its performance is consistent with that understanding, it
      is precise within usual performance standards, dependable, accurate at both group
      and individual levels within reasonable performance standards, and its accuracy
      is attributable to the well-grounded understanding. These results provide strong
      evidence that the Food Security Supplement provides valid measurement of food
      insecurity and hunger for population and individual uses. Further validation
      research is required for subgroups of the population, not yet studied for
      validation purposes, to establish validity for monitoring population changes in
      prevalence and to develop and validate robust and contextually sensitive measures
      in a variety of countries that reflect how people experience and think about food
      insecurity and hunger.

PMID- 10064320
TI  - Measuring food insecurity and hunger in the United States: development of a
      national benchmark measure and prevalence estimates.
AB  - Since 1992, the U.S. Department of Agriculture Food and Nutrition Service (FNS)
      has led a collaborative effort to develop a comprehensive benchmark measure of
      the severity and prevalence of food insecurity and hunger in the United States.
      Based on prior research and wide consultation, a survey instrument specifically
      relevant to U.S. conditions was designed and tested. Through its Current
      Population Survey (CPS), the U.S. Bureau of the Census has fielded this
      instrument each year since 1995. A measurement scale was derived from the data
      through fitting, testing and validating a Rasch scale. The unidimensional Rasch
      model corresponds to the form of the phenomenon being measured, i.e., the
      severity of food insufficiency due to inadequate resources as directly
      experienced and reported in U.S. households. A categorical measure reflecting
      designated ranges of severity on the scale was constructed for consistent
      comparison of prevalence estimates over time and across population groups. The
      technical basis and initial results of the new measure were reported in September
      1997. For the 12 months ending April 1995, an estimated 11.9% of U.S. households
      (35 million persons) were food insecure. Among these, 4.1% of households (with
      6.9 million adults and 4.3 million children) showed a recurring pattern of hunger
      due to inadequate resources for one or more of their adult and/or child members
      sometime during the period. The new measure has been incorporated into other
      federal surveys and is being used by researchers throughout the U.S. and Canada.

PMID- 10064321
TI  - Economic determinants and dietary consequences of food insecurity in the United
      States.
AB  - This paper reviews recent research on the economic determinants and dietary
      consequences of food insecurity and hunger in the United States. The new Current
      Population Study (CPS) food insecurity and hunger measure shows that hunger rates
      decline sharply with rising incomes. Despite this strong relationship, confirmed
      in other national datasets, a one-to-one correspondence between poverty-level
      incomes and hunger does not exist. In 1995, 13.1% of those in poverty experienced
      hunger and half of those experiencing hunger had incomes above the poverty level.
      Panel data indicate that those who are often food insufficient are much more
      likely than food-sufficient households to have experienced recent events that
      stress household budgets, such as losing a job, gaining a household member or
      losing food stamps. Cross-sectional work also demonstrates the importance of food
      stamps because benefit levels are inversely related to food insufficiency.
      Concern for the dietary consequences of domestic food insufficiency is well
      placed; recent research shows that the odds of consuming intakes <50% of the
      recommended dietary allowance (RDA) are higher for adult women and elderly
      individuals from food-insufficient households. Preschoolers from food
      insufficient households do not consume significantly lower amounts than those
      from food-sufficient households, but mean intakes for the rest of members in
      those very same households are significantly lower for the food insufficient.
      This research highlights the importance of food insecurity and hunger indicators,
      further validates the use of self-reported measures and points to areas of need
      for future research and interventions.

PMID- 10064322
TI  - Nutrition and health outcomes associated with food insecurity and hunger.
AB  - This paper explores how food insecurity and hunger relate to health and nutrition
      outcomes in food-rich countries such as the United States. It focuses on two
      subgroups of the population for whom data are available: women of childbearing
      age and school-age children. Special consideration is given to examining how food
      insecurity relates to these outcomes independently of socioeconomic status and
      poverty. In a population-based sample of women of childbearing age, the least
      severe level of food insecurity (household food insecurity) was correlated with
      higher body mass index (BMI), controlling for other available and known
      influences on obesity including income level. In low income school-age children
      from two large urban areas of the U.S., risk of hunger and hunger were associated
      with compromised psychosocial functioning, controlling for maternal education and
      estimated household income. The nutrition and health consequences of food
      insecurity comprise a potentially rich area for future, socially relevant
      research in the field of nutritional sciences.

PMID- 10064323
TI  - Food insecurity: consequences for the household and broader social implications.
AB  - A conceptual framework showing the household and social implications of food
      insecurity was elicited from a qualitative and quantitative study of 98
      households from a heterogeneous low income population of Quebec city and rural
      surroundings; the study was designed to increase understanding of the experience
      of food insecurity in order to contribute to its prevention. According to the
      respondents' description, the experience of food insecurity is characterized by
      two categories of manifestations, i.e., the core characteristics of the
      phenomenon and a related set of actions and reactions by the household. This
      second category of manifestations is considered here as a first level of
      consequences of food insecurity. These consequences at the household level often
      interact with the larger environment to which the household belongs. On a chronic
      basis, the resulting interactions have certain implications that are tentatively
      labeled "social implications" in this paper. Their examination suggests that
      important aspects of human development depend on food security. It also raises
      questions concerning the nature of socially acceptable practices of food
      acquisition and food management, and how such acceptability can be assessed.
      Guidelines to that effect are proposed. Findings underline the relevance and
      urgency of working toward the realization of the right to food.

PMID- 10064324
TI  - Symposium: Causes and Etiology of Stunting. Introduction.

PMID- 10064325
TI  - Separate and joint effects of micronutrient deficiencies on linear growth.
AB  - Recent studies have investigated the effect of micronutrient deficiencies on
      growth stunting, with special attention toward the effect of zinc, iron, vitamin
      A and iodine deficiencies. In Mexico, the prevalence of growth stunting in
      children <5 y old is approximately 24%; it is higher in rural areas and lower in
      urban areas. In an initial study, the effect of zinc and/or iron supplementation
      on linear growth was investigated in a longitudinal, placebo-controlled design.
      After 12 mo of supplementation, there was no difference between the groups
      supplemented with zinc, iron or zinc plus iron and the placebo group. At
      baseline, 82% of the children in this study were deficient in at least two out of
      the five micronutrients that were determined, and 73% were anemic. In another
      study, a mixture of those micronutrients that were documented to be lacking in
      Mexican children was formulated in a supplement and given to Mexican children
      over a period of 12 mo in a longitudinal, placebo-controlled, supplementation
      design. Children in the low and medium socioeconomic status grew about 1 cm more
      than similar children in the placebo group. This difference was not found in
      children of high socioeconomic status. It is suggested that, in most cases,
      growth stunting is associated with marginal deficiencies of several
      micronutrients and that in populations with multiple micronutrient deficiencies,
      the effect on linear growth of supplementation with single nutrients will not be
      significant. Supplementation with multiple micronutrients is expected to be more
      effective, but even in that case the actual increment in height was less than the
      expected potential increment.

PMID- 10064326
TI  - Burden of infection on growth failure.
AB  - The high prevalence of infections among children living in poor areas of
      developing countries impairs linear growth in these populations. Acute, invasive
      infections, which provoke a systemic response (e.g., dysentery and pneumonia),
      and chronic infections, which affect the host over a sustained period (e.g., gut
      helminth infections), have a substantial effect on linear growth. Such infections
      can diminish linear growth by affecting nutritional status. This occurs because
      infections may decrease food intake, impair nutrient absorption, cause direct
      nutrient losses, increase metabolic requirements or catabolic losses of nutrients
      and, possibly, impair transport of nutrients to target tissues. In addition,
      induction of the acute phase response and production of proinflammatory cytokines
      may directly affect the process of bone remodeling that is required for long bone
      growth. Infection of cells directly involved in bone remodeling (osteoclasts or
      osteoblasts) by specific viruses may also directly affect linear growth. Many
      interventions are possible to diminish the effect of infection on growth.
      Prevention of disease through sanitation, vector control, promotion of breast
      feeding and vaccination is crucial. Appropriate treatment of infections (e.g.,
      antibiotics for pneumonia) as well as supportive nutritional therapy (again
      including breast-feeding) during and after recovery, is also important. Targeted
      therapeutic interventions to decrease the prevalence of gut helminth infections
      may also be appropriate in areas in which such infections are widespread. Such
      interventions are of public health benefit not only because they reduce the
      incidence or severity of infections, but also because they decrease the long-term
      detrimental effect of malnutrition on populations.

PMID- 10064327
TI  - Predicting longitudinal growth curves of height and weight using ecological
      factors for children with and without early growth deficiency.
AB  - Growth curve models were used to examine the effect of genetic and ecological
      factors on changes in height and weight of 225 children from low income, urban
      families who were assessed up to eight times in the first 6 y of life. Children
      with early growth deficiency [failure to thrive (FTT)] (n = 127) and a community
      sample of children without growth deficiency (n = 98) were examined to evaluate
      how genetic, child and family characteristics influenced growth. Children of
      taller and heavier parents, who were recruited at younger ages and did not have a
      history of growth deficiency, had accelerated growth from recruitment through age
      6 y. In addition, increases in height were associated with better health, less
      difficult temperament, nurturant mothers and female gender; increases in weight
      were associated with better health. Children with a history of growth deficiency
      demonstrated slower rates of growth than children in the community group without
      a history of growth deficiency. In the community group, changes in children's
      height and weight were related to maternal perceptions of health and temperament
      and maternal nurturance during feeding, whereas in the FTT group, maternal
      perceptions and behavior were not in synchrony with children's growth. These
      findings suggest that, in addition to genetic factors, growth is dependent on a
      nurturant and sensitive caregiving system. Interventions to promote growth should
      consider child and family characteristics, including maternal perceptions of
      children's health and temperament and maternal mealtime behavior.

PMID- 10064328
TI  - Role of intergenerational effects on linear growth.
AB  - Current knowledge on the role of intergenerational effects on linear growth is
      reviewed on the basis of a literature search and recent findings from an ongoing
      study in Guatemala. Fourteen studies were identified, most of which examined the
      intergenerational relationships in birth weight. Overall, for every 100 g
      increase in maternal birth weight, her child's birth weight increased by 10-20 g.
      The study samples were primarily from developed countries, and birth weight data
      were extracted from hospital records and/or birth registries. Among the few
      studies that examined associations between the adult heights of parents and their
      offspring, correlation coefficients of 0.42-0.5 were reported. None of the
      studies examined intergenerational relationships in birth length or linear growth
      patterns during early childhood, preadolescence and/or adolescence. Prospectively
      collected data from long-term studies being carried out in rural Guatemala
      provide the first evidence of intergenerational relationships in birth size in a
      developing country setting. Data were available for 215 mother-child pairs.
      Maternal birth size was a significant predictor (P < 0.05) of child's birth size
      after adjusting for gestational age and sex of the child and other potential
      confounders. Child's birth weight increased by 29 g/100 g increase in maternal
      birth weight which is nearly twice that reported in developed countries.
      Similarly, child's birth length increased by 0.2 cm for every 1 cm increase in
      mother's birth length. The effect of maternal birth weight remained significant
      even after adjusting for maternal adult size. More evidence from developing
      countries will help explain the underlying mechanisms and identify appropriate
      interventions to prevent growth retardation.

PMID- 10064329
TI  - Symposium: Interactions of Diet and Nutrition with Genetic Susceptibility in
      Cancer. Overview.

PMID- 10064330
TI  - The role of interindividual variation in human carcinogenesis.
AB  - The process of chemical carcinogenesis is a complex multistage process initiated
      by DNA damage in growth control genes. Carcinogens enter the body from a variety
      of sources, but most require metabolic activation before they can damage DNA.
      There are multiple protective processes that include detoxification and
      conjugation, DNA repair and programmed cell death. Most of these functions
      exhibit wide interindividual variation in the population and thus are thought to
      affect cancer risk. The role of gene-environment interactions is being explored,
      and current data indicate that genetic susceptibilities can modify carcinogen
      exposures from the diet and tobacco smoking, although much more data exist for
      the latter. This review addresses the relationships of human carcinogenesis to
      these interindividual differences of phase I, phase II and DNA repair enzymes.

PMID- 10064331
TI  - Diet, genetic susceptibility and human cancer etiology.
AB  - There is evidence that high penetrance hereditary genes cause a number of
      relatively uncommon tumors in the familial setting, whereas common cancers are
      influenced by multiple loci that alter susceptibility to cancer and other
      conditions. The latter category of genes are involved in the metabolism of
      carcinogens (activation, detoxification) as well as those that interact with
      dietary exposure. This paper will consider some of the basic principles in
      studying susceptibility genes and provide a few examples in which they interact
      with dietary components.

PMID- 10064332
TI  - MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and
      adenoma among U.S. men and women: an example of gene-environment interactions in
      colorectal tumorigenesis.
AB  - Our studies on interactions of a folate-metabolizing gene polymorphism and
      dietary intake in colorectal tumorigenesis demonstrate the potential importance
      of studying interactions between genotype and environmental exposure in relation
      to cancer risk. We observed an inverse association of a polymorphism (667C --> T,
      ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with
      colorectal cancer but not with colorectal adenomas. The inverse association of
      methionine and adverse association of alcohol with colorectal cancer were
      stronger among val/val individuals. These interactions were not present in
      studies of colorectal adenomas. Our studies illustrate that studying gene
      environment interactions in relation to cancer can be of importance in clarifying
      cancer etiology as well as pointing to preventive dietary modifications.

PMID- 10064333
TI  - Glutathione-S-transferase (GSTM1) genetic polymorphisms do not affect human
      breast cancer risk, regardless of dietary antioxidants.
AB  - Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites
      and reactive oxygen species (ROS) produced through a number of mechanisms.
      Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in
      a lack of enzyme activity. Because there are indications that ROS may be involved
      in breast carcinogenesis, we sought to determine whether the GSTM1 null allele
      was associated with increased breast cancer, particularly among women with lower
      consumption of dietary sources of alpha-tocopherol, carotenoids and ascorbic
      acid. In a study of diet and cancer in western New York, women with primary,
      incident, histologically confirmed breast cancer (n = 740) and community controls
      (n = 810) were interviewed and an extensive food-frequency questionnaire
      administered. A subset of these women provided a blood specimen. DNA was
      extracted and genotyping performed for GSTM1. Data were available for 279 cases
      and 340 controls. The null allele did not increase breast cancer risk, regardless
      of menopausal status. There were also no differences in associations between the
      polymorphism and risk among lower and higher consumers of dietary sources of
      antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic
      polymorphisms are not associated with breast cancer risk, even in an environment
      low in antioxidant defenses.

PMID- 10064334
TI  - Symposium: Steroid Hormone Receptor and Nutrient Interactions: Implications for
      Cancer Prevention. Introduction.

PMID- 10064335
TI  - Glucocorticoid mediation of dietary energy restriction inhibition of mouse skin
      carcinogenesis.
AB  - Dietary energy restriction (DER) inhibits carcinogenesis in numerous animal
      models. DER is a potent and reproducible inhibitor of two-stage mouse skin
      carcinogenesis when administered during the promotion phase. Previous research
      demonstrated that adrenalectomy abolished cancer prevention by food restriction.
      Several lines of evidence suggest that glucocorticoid elevation in the DER mouse
      mediates the prevention of skin cancer. Our research tested the hypothesis that
      elevated glucocorticoid hormone activates the glucocorticoid receptor (GR) and
      that this activated receptor interferes with the activator protein-1 (AP-1)
      transcription factor. Induction of AP-1 by the phorbol ester tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) is essential to tumor promotion. We have
      been unable to demonstrate elevated activated GR in the epidermis of the DER
      mouse, perhaps because only indirect strategies have been possible with the use
      of epidermis from DER mice. However, DER blocked the induction of AP-1 and c-jun,
      a constituent protein of AP-1, in the epidermis of mice. Current studies are
      focused on the inhibition of signaling down the MAP-1/Raf-1 kinase pathway that
      leads to induction of constituent proteins of AP-1, including c-Jun. Although
      several pathways lead to the induction of AP-1 transcriptional activity, the MAP
      1/Raf-1 pathway can be activated by protein kinase C (PKC); previous studies from
      our laboratory demonstrated an inhibition of PKC activity and a reduction in
      selected isoforms of PKC in the epidermis of the DER mouse. Our current working
      hypothesis is that elevated glucocorticoid hormone in the DER mouse reduces the
      amount and activity of PKC isoforms important in the activation of MAP-1/Raf-1
      kinase pathway. We propose that this results in attenuation in the induction of
      the AP-1 transcription factor by TPA. Because AP-1 induction by TPA is obligatory
      for mouse skin promotion, we propose this as an essential component of the
      mechanism of DER prevention of mouse skin carcinogenesis.

PMID- 10064336
TI  - Peroxisome proliferator-activated receptors: a critical link among fatty acids,
      gene expression and carcinogenesis.
AB  - It has been known for many years that long-chain fatty acids derived from
      endogenous metabolism and/or nutrition can act as second messengers and
      regulators of cell signaling pathways. For example, fatty acids regulate the
      activity of protein kinase C (PKC) in a mechanism distinct from activation by
      diacylglycerol. Like PKC activators such as phorbol esters, essential fatty acids
      activate PKC and in doing so modulate the activity of growth factor receptors
      such as epidermal growth factor receptor (EGFR). Unsaturated fatty acids can
      inhibit GTPase activating protein, thereby quenching signals from p21-ras. These
      studies have shown that fatty acids can influence numerous signaling pathways and
      that these small lipophilic substances may be ancient second messengers. Fatty
      acids are also known modulators of the carcinogenic process, showing distinct
      tissue-specific pro- or anticancer effects. However, the reason for such a
      dichotomous effect on cellular processes has not been adequately described. In
      this article, the inclusion of a steroid hormone receptor-signaling pathway in
      mediating fatty acids' effects will be summarized. This signaling molecule has
      been deemed the peroxisome proliferator-activated receptor (PPAR) and has been
      extensively examined in regard to its response to xenobiotic, fatty acid-like
      chemicals (peroxisome proliferators, PP). PP, like fatty acids, activate PPAR and
      modulate tissue-specific responses. The goal of this review is to describe a
      potential role for PPAR in mediating the effects of fatty acids on gene
      expression, cell growth, differentiation and apoptosis.

PMID- 10064337
TI  - Transcriptional targets of the vitamin D3 receptor-mediating cell cycle arrest
      and differentiation.
AB  - We are exploring the mechanism of action of the hormonal form of the nutrient
      vitamin D, 1,25(OH)2D3, and its cognate nuclear receptor at the level of gene
      control. In doing so, we have focused on a dual track as follows: 1) to define
      the vitamin D3 receptor (VDR) function and structure by examining its various
      actions at the molecular level; and 2) to isolate and characterize VDR target
      genes that might be playing key roles in mediating vitamin D growth suppression
      and differentiation in responsive cells, specifically, the elucidation of vitamin
      D target genes as they relate to myeloid differentiation. Here, we will summarize
      some of our recent results from both tracks because a detailed understanding of
      how VDR functions as a ligand-regulated transcription factor will allow us to
      study its actions on these newly discovered genes more effectively.

PMID- 10064338
TI  - Modulation of estrogen action in the rat pituitary and mammary glands by dietary
      energy consumption.
AB  - We are investigating the mechanisms through which estrogens induce development of
      prolactin (PRL)-producing pituitary tumors and mammary carcinomas in rats and how
      these mechanisms are affected by dietary energy consumption. The hypothesis under
      examination is that dietary energy restriction inhibits tumorigenesis in estrogen
      responsive tissues by altering cellular responsiveness to estrogenic hormones. In
      the Fischer 344 (F344) rat strain, a 40% restriction of energy consumption
      virtually abolishes development of estrogen-induced pituitary tumors. Inhibition
      of pituitary tumorigenesis in the F344 strain by energy restriction results from
      modulation of estrogen regulation of cell survival, not cell proliferation. In
      contrast, energy restriction has no inhibitory effect on estrogen-induced
      pituitary tumor development in the ACI rat strain. However, energy restriction
      markedly inhibits induction of mammary carcinomas in female ACI rats treated with
      17beta-estradiol. Data presented herein indicate that dietary energy restriction
      modulates the responsiveness of specific cell populations to estrogenic hormones
      and thereby inhibits estrogen-induced tumorigenesis in a manner specific to both
      rat strain and tissue.

PMID- 10064339
TI  - Advances in cardiac imaging.
AB  - Silent myocardial ischemia is the most important target of a variety of imaging
      modalities. The ultimate technology would include anatomic, functional, and
      myocardial perfusion information. Ultrafast computer tomography, as this time, is
      the best modality for studying the coronary arteries. Positron Emission
      Tomography remains the gold standard for studies of myocardial blood flow and
      myocardial utilization.

PMID- 10064340
TI  - Improved densitometric analysis of ventricular volumes in on-line digital cardiac
      imaging.
AB  - In digital angiocardiography left ventricular volumes are routinely calculated by
      the area-length-method (ALM) which is considered to be a standard and with which
      other techniques are compared. Densitometric analysis (DENS) is an alternative
      method and can be performed on-line but may lead to erroneous results. A novel
      technique of densitometric calculation of left ventricular enddiastolic and
      endsystolic volume (LVEDV resp. LVESV) is presented. Digital images were analyzed
      by measuring densities of iodine signals and transforming these into calculated
      volumes by applying appropriate computer algorithms. The evaluation of volumes in
      cardiac models demonstrated significant correlations between true volumes and
      both DENS and ALM. An algorithmic approach to volume correction in patient
      evaluation of left ventricular volumes was drawn from the linear regression
      analysis of DENS and true volumes in the cardiac models. LVEDV and LVESV
      calculated by DENS correlated significantly with volumes determined by ALM in
      patients (r=0.78 resp. r=0.83) but showed a systematic underestimation for
      volumes > or =45 ml without densitometric correction. Following correction for
      DENS, an improvement in calculation was observed for volumes < or =200 ml without
      systematic deviations. In conclusion, our study demonstrates that corrected
      densitometric volumetry offers the potential for a reliable on-line analysis of
      enddiastolic and endsystolic volumes. Modest, but no systematic deviations for
      densitometric analysis may be anticipated in myogene dilatation with volumes
      larger than 200 ml. However, when comparing both DENS and ALM, method-related
      errors of both techniques are present and account for volume deviations.

PMID- 10064341
TI  - Early single centre experience with 192 Sorin Bicarbon valves.
AB  - In 1990 Sorin Biomedica introduced a new pyrolytic bileaflet heart valve, the
      Bicarbon, developed using innovative design concepts with new materials, housing,
      hinge mechanism, leaflet curvature and sewing ring construction. From June 1991
      to May 1995, 192 bicarbon valves were implanted in 177 patients by one team. The
      patient population was 102 males and 75 females with an age range from 16 to 82
      years (mean 62.5 years). Ninety-six were AVR, 68 MVR, 12 double valve
      replacements, 2 patients received another type of bileaflet valve as did the
      triple valve replacement. Overall hospital mortality was 5.2%. For MVR the
      mortality was 12.7%; for AVR it was 4.7%. There were no deaths associated with
      double or triple valve replacement. Five deaths were at reoperation, 2 at
      emergency operation, 1 aortic dissection, 2 for endocarditis, none of the deaths
      were valve related. One patient had a haemorrhage due to inadequate control of
      Warfarin therapy. Four valves were explanted: 3 mitrals for paravalvular leaks
      and 1 aortic for endocarditis. No patients showed any evidence of thromboembolic
      complications and there were no late deaths. All the surviving patients have
      improved their preoperative clinical status. Maximum follow-up is nearly 4 years,
      mean 32 months (range 1-47). Twenty one patients underwent haemodynamic
      evaluation by Doppler echocardiography. The mean pressure drop across 12 mitral
      valves was 8.34 mmHg (mean size 29.7 mm) and for 9 aortic valves it was 15.85
      mmHg (mean size 23). Based on these results we are of the opinion that the
      Bicarbon valve is equivalent to the best of other bileaflet valves currently
      available.

PMID- 10064342
TI  - Results of a 1 to 31 years follow-up after aortic valve replacement in 2327
      patients.
AB  - We studied the outcome of 2327 patients after aortic valve replacement from
      October 1962 to December 1993. 1840 mechanical (mostly STJ bi-leaflet and BS
      tilting disc valves) and 487 biological (IS and CE valves) prostheses were
      implanted. The mean follow-up period of 1458 surviving patients was 7.1 years.
      There were 688 non-survivors and 181 lost cases. The mean age was 50.1 years, 73%
      of the patients were male and 27% were female. Early mortality was about 20% in
      the 1960's and about 4.5% in the last years. Mortality following valve
      replacement was influenced by preoperative NYHA classification, cardiac index,
      pressure gradient and simultaneous CHD. The long term results of all valves
      showed a survival rate of 80% after 5 years, 73% after 10 and 60% after 15 years
      following operative treatment. There was no significant difference in survival
      rates between all mechanical and biological valves. Non-lethal complications of
      all mechanical valves showed no significant difference but there was a clearly
      lower rate of paraprosthetic leakages, haemolysis and thromboembolism in
      biografts. The biological valves showed a high rate of degeneration (2.7%/pty).
      Reoperation was performed in 170 patients. Most valve changes consisted of
      biological to mechanical and mechanical to mechanical valves. The main reason of
      reoperation was degeneration (biological), paraprosthetic leakage and haemolysis
      (mechanical). The cause of death of the 688 non-survivors was valve related in
      17.9%. 37% of these were due to thromboembolism and 38% due to bleeding. 55.6% of
      survivors (group 2) could be ascribed to NYHA class III and 17.2% to class IV
      prior to operation. Postoperative outcome demonstrated an improvement in NYHA
      classification in about 80%. Of surviving patients 80% pronounced an increase of
      physical activity after operation.

PMID- 10064343
TI  - Long-term results after aortic valve replacement with the Mitroflow pericardial
      valve.
AB  - From September, 1986 through December, 1989, 121 patients underwent aortic valve
      replacement with the Mitroflow pericardial valve. There were 70 males (58%) and
      51 females (42%), with an average age of 71 years (range 50-85 years). Reported
      here are the long-term results from these patients. Concomitant cardiac
      procedures were performed in addition to aortic valve replacement in 38 patients
      (31%); Coronary artery revascularization in 27 patients (22%); 4 patients (3%)
      had combination aortic/mitral valve replacement; mitral valve reconstruction in 4
      patients (3%) and 3 patients (2%) had other additional procedures. Following
      surgery, standard postoperative examinations were performed every six month for 2
      years; then yearly thereafter. At these times valvular function assessed
      echocardiographically. Current follow-up extends to 7 years (mean = 5 years) for
      surviving patients. Postoperative mortality for all observation period is as
      follows: Early deaths (> or =30 days postop) = 6 patients (5%), late death (>30
      days) = 18 patients (15%). Valve-related causes of death included cerebral insult
      (thromboembolism) in two patients (one 10 months, other 15 months
      postoperatively). Postoperative valve-related morbidity included prosthetic
      endocarditis (1 patient) one year postoperatively; degenerative prosthetic
      failure (1 patient) 27 months postop; cusp tear (1 patient) with minimal
      hemodynamic changes after four years. In the patients with endocarditis and
      failure, a second successful operation corrected the problem. Also, in two
      patients antithrombolitic therapy related hemor-rhage occurred (one 9 months, the
      second 11 months postoperatively). This therapy was a result of atrial
      fibrillation, and we do not recommended it. In conclusion, we find that the
      Mitroflow pericardial heart valve gives adequate long-term results, especially in
      elderly patients with a small aortic ring, with very satisfactory quality of
      life.

PMID- 10064344
TI  - Results of mechanical prosthetic valve replacement in active valvular
      endocarditis.
AB  - To evaluate the results of mechanical prosthetic valve replacement for active
      endocarditis 71 patients were reviewed. They were treated surgically between 1988
      and 1993 in our institution. Mechanical valves were used in 54 patients (group 1)
      and bioprosthetic valves were used in 17 patients (group 2). In terms of
      demographic, clinical and surgical variables prior to operation groups were
      statistically the same. Follow up ranged from 2-63 months averaged 21 months.
      This study was carried out to: asses cardiac status postoperatively and assess
      the rate of mortality, recurrency and reoperations. METHODS: Evaluation of
      cardiac status was assessed on the basis of symptoms and findings by examination,
      ECG, X-ray, echocardiography, and laboratory tests. Data analysis was done by
      means of statistical tests like: Student's "t"-test, Fisher exact test, one sided
      test of difference between two percentages, Kaplan Meyer survival analysis and
      Cox test. RESULTS: 4-year mortality was 20% in group 1 comparing to 28,6% in
      group 2, when early mortality were 13% in group 1 comparing to 17% in group 2.
      These differences were not significant. The recurrency rate was 8,5% in group 1
      comparing to 28,6% in group 2 which was statistically significant (p=0.028).
      Especially early recurrency rates differed significantly between groups and were
      4,2% in group 1 comparing to 21% in group 2 (p=0.022). The reoperations rate was
      4,2% in group 1 comparing to 21% in group 2 which was statistically significant
      (p=0.022). Clinical status showed satisfactory values and significant improvement
      in both groups, slightly better after mechanical valve replacement. CONCLUSION:
      It is concluded that mechanical valve is recommended for valve replacement in
      active valvular endocarditis first of all due to low recurrency and reoperation
      rate.

PMID- 10064345
TI  - Aortic stenosis in the elderly: result of aortic valve replacement.
AB  - Forty-six patients, 24 male and 22 females, with a mean age of 78.4 years (range
      75 to 88) underwent aortic valve replacement (AVR) for severe calcific aortic
      stenosis during a five year period. Twenty-six patients (56.5%) had combined
      aortic valve replacement/coronary artery bypass (AVR/CABG) procedures. Bovine
      pericardial or porcine bioprostheses were used in 47.8% of cases. The mean length
      of stay in the intensive care unit was 2.9 days (range 2-13) with a mean hospital
      stay of 12.6 days (range 6-41). Operative mortality rate was 6.5% (3 patients),
      all in the AVR/CABG group. Complications included pneumonia (8.7%), stroke
      (6.5%), and complete heart block requiring pacemaker insertion (6.5%). Follow-up
      of survivors from 11-69 months (mean 34.6) shows 92.9% survival, with 87.2% in
      New York Heart Association (NYHA) Class I and II. Aortic valve replacement in the
      elderly population has an acceptable mortality rate and is associated with
      significantly improved quality of life over the intermediate term.

PMID- 10064346
TI  - One hundred patients' experience with the Jyros valve.
AB  - The ideal mechanical valve abolishes all potential areas for blood stagnation and
      hence the potential for micro-emboli and clot formation. This problem has been
      addressed by the innovative design of the Jyros valve which has evolved from the
      technology available from Russian space research. The valve comprises two
      pyrolytic carbon leaflets which can rotate within the solid carbon housing to
      either align themselves to the optimum haemodynamic configuration, or to respond
      by rotation either continuous or intermittent, according to the degree of swirl
      on the inflow profile. This Jyros mechanical heart valve has been assessed in
      vivo at the London Chest Hospital since August 1992 where the series of
      unselected patients constitutes the largest single user experience available. 107
      valves were implanted in 100 patients of age range 33 to 80 years. 23 patients
      were re-replacement for failed xenograft and 26 underwent concomitant
      revascularisation. 92 patients left hospital and 4 died later all from non-valve
      related causes. Two valves were explanted for endocarditis (one pre-existing) but
      successfully re-replaced. There have been no late thrombo-embolic events. Two
      patients with AVR & CABG had strokes at 8 months. There is no excessive
      haemolysis in excess of that detected for any mechanical valve nor any mechanical
      valve-related failure. Rotation of the valve is variable and can be visualised by
      2D and M mode echo and by X-ray screening as the leaflets are impregnated with
      Boron carbide. Half of the valves rotate constantly and a quarter intermittently.
      There appears to be no disadvantage to patients in whom no valve rotation could
      be demonstrated. We have found that the theoretical potential of performance have
      been achieved.

PMID- 10064347
TI  - Early experience with the Sorin bileaflet prosthetic valve.
AB  - Between 1.6.1991 and 31.5.1995, 62 patients underwent heart valve replacement
      with Sorin Bicarbon bileaflet prosthetic valve, age 16-83 years (mean 60.5). The
      valve disease was rheumatic in 37 cases, degenerative in 17, congenital in 4 and
      miscellaneous etiologies in the other 4. The valve lesion was AS in 24 patients,
      AR in 5, AR+MS in 2, MS in 13, MR+MS in 6, MR in 6, tricuspid prosthetic stenosis
      in 1, A+M disease in 3, and a clotted prosthetic valve (Sorin disc) in 1. CAD was
      present in 14 patients (23%) and AF in 19 (31%). 11 had moderate pulmonary
      hypertension and 4 severe. Preoperatively 6 patients were in FC II, 40 in FC III
      and 16 in FC IV. Operative procedures included AVR 18, AVR+CABG 13, AVR+T
      annuloplasty 1, AVR and open M valvotomy 1, MVR 7, MVR+T annuloplasty 7, MVR+AVR
      (Medtronic) 1, MVR+AVR 1, TVR, prosthetic valve replacement 1, and MVR+CABG 1.
      Hospital mortality was 3 (4.8%) -- one due to ruptured A-V groove and two due to
      LoCO. Postoperative complications: LoCO necessitating IABP -- 3 patient; 3
      transient CVA and 1 CVA with hemiplegia. One patient had aortic prosthetic valve
      endocarditis 18 months following the operation necessitating reoperation. Other
      cases were treated for positive blood cultures. One patient had CVA after
      anticoagulant were discontinued. 28 patients are in FC I, 22 in H, 4 in III and 1
      in IV. 4 patients are lost to follow-up. These data suggest that the Sorin
      Bicarbon Prosthetic valve can be safely and effectively used for heart valve
      replacement.

PMID- 10064348
TI  - Mitral valve surgery through right thoracotomy.
AB  - Two years ago we had, for technical reason to resuscitate right thoracotomy (RT)
      to approach the mitral valve. Since then we have used it in 23 patients. 18 of
      them had had at least one operation through a medium sternotomy. In 5 cases the
      right approach was electively used, as first choice to repair or replace the
      mitral valve. Intracardiac surgery was performed routinely with moderate
      hypothermia and controlled ventricular fibrillation with the aorta unclamped.
      Only in one case, an unexpected aortic incompetence forced us to cross-clamp the
      aorta and replace the valve using crystalloid cold cardioplegia. 14 patients
      underwent mitral valve replacement. In 5 cases a leaking mitral prosthesis was
      successfully reattached and in 4 cases the native valve was repaired. 2 patients
      died (9%) for reasons unrelated to the technique. We did not have any case of air
      embolism. CONCLUSION: 1) RT is very useful to approach the mitral valve,
      specially in patients who previously had: a) several sternotomies, b)
      postoperative mediastinitis, specially if treated by omentoplasty, c) coronary
      artery bypass; 2) the good view to the mitral valve obtained with the aorta
      unclamped, make us think if the mitral repair should elective done through this
      approach.

PMID- 10064349
TI  - Evaluation of surgical effect on cardiovascular anomalies associated with
      corrected transposition of great arteries.
AB  - From September, 1985 to April, 1994, 33 patients underwent surgical repair of
      corrected transposition of the great arteries associated with other congenital
      heart anomalies. Of them, 31 patients were SLL type, the other 2 patients were
      attributed to IDD type. Operations were performed on ventricular septal defect in
      28 patients, atrial septal defect in 15, pulmonary stenosis in 29 and two had
      valvuloplasty for left atrioventricular valve regurgitation, patent ductus
      arteriosus closure was performed on one and modified Fonton procedure on one.
      There were five peri-operative deaths being 15.7% of operative morbility; late
      death was only one patient. The following-up of the survival 27 patients for 2
      months to 9 years showed a satisfactory results.

PMID- 10064350
TI  - One-year experience with the Edwards stentless "Prima" aortic bioprosthesis.
AB  - The aortic stentless bioprothesis are expected to have an improved hemodynamic
      function because of their lack of a sewing ring and stents. From April 1993 to
      March 1994 we implanted aortic Edwards "Prima" stentless bioprotheses in 21
      patients suffering from aortic valve disease. In some patients additional cardiac
      procedures (CABG, MVR, tricuspid valve anuloplasty) were performed. The patients'
      age ranged from 56 to 78 years. The size of the bioprothesis ranged from 23 mm to
      29 mm in diameter. We used either the subcoronary or the "mini-root" continuous
      suture technique. Aortic cross-clamp time ranged from 52 min to 128 min. There
      was no operative mortality. The intraoperative measurements showed that the
      pressure gradient across the aortic valve was very low or even undetectable. The
      echocardiographic control after 1 year revealed very good valve function. Our
      initial experience with this new valve shows a very good short-term result with
      an only slightly longer cross-clamp time. Since the valve has not been available
      for a long line, long-term results could not yet be observed.

PMID- 10064351
TI  - Allograft replacement of the aortic valve for active endocarditis.
AB  - PURPOSE: In the 50 months preceding March 1995, 35 adult patients underwent
      aortic valve replacement with a cryopreserved human aortic valve allograft. Nine
      of these patients had active endocarditis. The remaining 26 patients had aortic
      valve pathology without active infection. This study consists of a comparison of
      these two groups. METHODS: One of the patients with active infection underwent
      inclusion technique replacement of the infected valve. The other eight valves
      were replaced with root-replacement technique. Of the 26 non-infected patients, 4
      valves were replaced with the inclusion technique, and the remaining 22 were
      replaced with the root-replacement technique. None of the patients are maintained
      on long-term anti-coagulation. RESULTS: We have followed the infected group an
      average of 32 months and the group without active infection has been followed an
      average of 27 months. There were two perioperative deaths in the nine patients
      with infected valves and no deaths in the group without active infection
      (Pearson's chi2 p<0.05). There have been no thromboembolic complications and no
      recurrent infections.

PMID- 10064352
TI  - Operative management of aortic arch aneurysm using profound hypothermia and
      circulatory arrest.
AB  - Since the first successful replacement of the aortic arch with perfusion of the
      head, various methods have been employed to preserve cerebral function during
      aneurysm operations. Although deep hypothermia was used for surgery of the aortic
      arch, as early as 1963, the introduction of prolonged circulatory arrest has
      simplified replacements of the aortic arch. Between October 1990 and September
      1993, 69 patients underwent aortic arch replacement for aneurysmal disease at the
      Dept. of Cardio-Thoracic Surg., University of Vienna. 52 patients had an acute
      dissection Type A, 17 patients were operated on electively. The patients age (48
      male, 21 female) ranged between 16 and 81 years. Primary diagnosis was
      hypertension (n=44), marfan (n=14), unknown (n=10) and trauma (n=1). Total
      cardiopulmonary bypass was established via femoral artery cannulation. All
      patients received Cortison and Thiopental for added cerebral protection. Deep
      hypothermia (12 degrees C), confirmed by 0-EEG, and circulatory arrest were
      induced in all patients. The aneurysm was opened longitudinally and a full
      thickness single patch or "island" of aortic wall, containing the origins of the
      three arch vessels, was constructed and anastomosed in a continuous fashion to an
      albumin coated graft. 68 patients survived the operation (intraoperative
      mortality 1%). The 30-day mortality was 23% (n=16). Twelve patients died of
      multiorgan failure, two patients of a stroke and two due to myocardial
      infarction. The mean cerebral circulatory arrest time was 32 minutes (range 11-61
      min.). Our experience with aortic arch replacements using profound hypothermia
      and circulatory arrest supports our contention, that it is the method of choice
      in this very difficult surgical field.

PMID- 10064353
TI  - Analysis of adhesion molecules in myocardial biopsies of cardiac allografts and
      coronary artery disease with CABG.
AB  - Interactions of leukocytes with vascular endothelium are important components of
      inflammation tissue reactions and have been implicated in cardiac transplant
      rejection and demonstrated to be mediated by cell adhesion molecules (CAM's). The
      expression of ICAM-1, VCAM-1 and E-selectin in human myocardium is variable and
      little is known about the expression of LFA-1 and Mac-1 during allograft
      rejection. This study investigated these CAM's in myocardial biopsies of
      transplanted hearts (HTX) and of coronary artery disease eligible for coronary
      artery bypass grafting (CABG) as non-inflammatory controls and explicitly
      examines vascular endothelium, cardiomyocytes and infiltrating cells.
      Immunohistochemistry was performed using the APAAP-method and directing specific
      mouse anti-human monoclonal antibodies against ICAM-1 (CD54), VCAM-1 (CD106), E
      selectin (CD62E), alpha-LFA-1 (CD11a), alpha-Mac-1 (CD11b), alpha-p150/95 (CD11c)
      and the beta2-integrin chain (CD18). CD18, LFA-1 (CD11a), Mac-1 (CD11b) and
      p150/95 (CD11c) were markedly expressed on infiltrating immunocytes in HTX
      compared to CABG where no expression of beta2-integrins was observed. Cardiac
      allografts demonstrated a strong expression of ICAM-1 on vascular endothelium and
      on infiltrating cells. ICAM-1 was not detected on cardiomyocytes. In CABG a weak
      expression of ICAM-1 was observed on endothelial cells but not on myocytes. VCAM
      1 was expressed on vascular endothelium and perivascular infiltrating cells in
      HTX but not in CABG. VCAM-1 was not found to be expressed on myocytes. There was
      no evidence for the presence of E-selectin in any of our biopsy specimens. Our
      study shows that the study of cell adhesion molecules adds to the
      pathophysiological understanding of inflammation after transplantation in cardiac
      disease. This offers a potential for the development of diagnostic tools and new
      therapeutic strategies.

PMID- 10064354
TI  - Emergency aortocoronary bypass grafting after failed percutaneous transluminal
      angioplasty versus elective bypass grafting.
AB  - From January 1980 through July 1994 fiftyseven patients underwent emergency
      coronary bypass grafting (CABG) after unsuccessful percutaneous transluminal
      angioplasty (PTCA), (Group I). This group was compared with a cohort of 57
      patients, who underwent elective coronary bypass grafting (Group II). The 2
      groups were compared in the rate of perioperative myocardial infarction, amount
      of blood loss, rethoracotomy because of bleeding, use of blood units and
      products, and length of stay in the intensive care unit. The data of both groups
      were retrospectively analyzed. Significant differences were observed:
      Perioprative myocardial infarction in group I was 18 patients (31%) versus 2
      patients (3%) in group II (p<0.0008). Amount of blood loss was higher (p<0.038),
      and the use of packed red blood cells was higher too (p<0.000) in group I. The
      length of stay in the intensive care unit was longer (p<0.000) in group I. Six
      rethoracotomies (10%) occured in group I versus 0 in group II. There were no
      hospital mortalities in either groups. We conclude there is a significant
      increase in morbidity in patients with emergency CABG after failed PTCA than
      patients who underwent elective CABG.

PMID- 10064355
TI  - The use of exogenous creatine phosphate for myocardial protection in patients
      undergoing coronary artery bypass surgery.
AB  - A key component in the development of ischemic functional and structural
      myocardial injury during cardiosurgical procedures is an inadequate cellular
      energy supply which occurs as a consequence of the cessation of oxidative
      metabolism. In such conditions high energy phosphates are rapidly depleted. As
      they play a critical role in the maintenance of cell viability and postischemic
      recovery of contractile function, their conservation is therefore a primary
      objective in any procedure designed to reduce ischemic injury. Exogenous
      administration of phosphocreatine (CP) has been suggested as being beneficial to
      the ischemic heart. The aim of present study was to evaluate the possible
      cardioprotective effect of exogenous CP during coronary artery surgery (CABG).
      Forty patients undergoing CABG procedure were randomly assigned to receive
      creatine phosphate-enriched (group I) or standard-St. Thomas' Hospital (group II)
      cardioplegic solution; each group comprised 20 patients. Group I received: 6.0 g
      of exogenous CP (Neoton) daily in two 20-min intravenous infusions during 3 days
      preoperatively; during surgical procedure they were administered standard
      cardioplegic solution enriched in CP at the concentration of 10 mmol/l and -- 2
      days postoperatively -- 4.0 g CP daily in two intravenous injections. Group II
      did not receive CP at all In both groups were analysed. Haemodynamic parameters.
      Continuous 48-h ECG recording (Holter monitoring) outcome. Laboratory values of
      serum CK and CK-MB. Inotropic support required (drugs, mechanical support).
      Ultrastructural findings (biopsy data). Statistical analysis was carried out
      using Student's "t"-test and the chi2 test. Values of p<0.05 were taken as the
      criterion of significant difference. The results of the study were: Significantly
      lower average number and energy of DC-shocks needed to restore cardiac function
      after cardiopulmonary bypass procedure in group 1. Statistically significant
      beneficial effect on the presence of ventricular arrhythmias during surgery and
      in early postoperative period in group I. Significantly lower requirements for
      inotropic drugs postoperatively in group I. Statistically significant lower
      degree of sarcolemmal damages in myocardial biopsies in group I. Concluding, the
      authors wish to state that: Exogenous phosphocreatine (Neoton) perioperative
      administration in coronary artery bypass patients reduced the need for inotropic
      drugs, which is clinically manifested in lower frequency of low cardiac output
      syndrome. Perioperative administration of exogenous CP improves
      electrophysiological stability of the myocardium. Advantageous clinical and
      electrophysiological effect of exogenous CP may result from its properties to
      protect sarcolemma of the cardiomyocytes.

PMID- 10064356
TI  - Coronary arteries bypass grafting with use of both internal thoracic arteries.
AB  - The internal thoracic artery is a preferred conduit for bypass grafting. While
      the single ITA grafting has been universally accepted -- the use of both ITA's
      remains controversial. The risk factors analysis based upon assessment of
      operative results and mid-term functional follow-up was performed. The clinical
      applicability of transthoracic B-mode ultrasonic imaging and Doppler spectrum
      analysis in the postoperative evaluation of use of two ITA's was investigated.
      From January 1989 to January 1993, 97 patients received bilateral ITA and
      additional vein or RGEA grafts at Groby Road Hospital, Leicester, UK. There were
      77 men (79.4%) and 20 women (20.6%) with mean age of 52.1+/-10.1 years. 19 cases
      were urgent. 14.4% of patients suffered from diabetes mellitus, 8.3% -- COAD and
      46.6% did not work because of angina. The average number of anastomoses per
      patient was 3. The operative mortality was 4.1%. Complications included:
      reoperation for bleeding=3.2%, sternal infection=6.5%, IABP=2.1%. There were no
      evidence of perioperative myocardial infarction. 80 patients were followed-up for
      26,5+/-13 months. 49 patients were in angina NYHA class I while preoperatively:
      7. 1 patient was in NYHA class III while preoperatively there were 40 patients.
      Nearly twice more patients worked, and more than three times fewer patients did
      not worked because of angina, comparing to preoperative period. With the use of
      colour Doppler technique the blood flow was measured in 78.3% of left and 74% of
      right ITA's. The average flow in left ITA was: 46.4+/-17 ml/min and 41.7+/-17
      ml/min in right ITA. The multivariate analysis for risk factors of bilateral
      ITA's grafting was performed. There were no risk factors for postoperative
      complications of bilateral internal thoracic arteries grafting in presented
      material. The risk of perioperative death is higher for patients with triple
      vessels disease than for patients with double vessels disease. Bilateral ITA
      grafting procedure has positive influence on patients working abilities.
      Percutaneous ultrasonic assessment of flow in ITA's used for bypass appears to be
      useful non-invasive investigation of their function.

PMID- 10064357
TI  - Idiopathic cystic medial necrosis of the coronary arteries leading to myocardial
      infarction, old and recent. Clinical pathologic correlation and historical
      review.
AB  - The reported case study is evidence to the fact that idiopathic cystic medial
      necrosis occurs more frequently in females, in particular young females, and in
      association with the post-partum state (female:male ratio 3:1). The case study
      documents also the fact that early recognition of this syndrome and workup with
      angiography may lead to a recognition timetable which will allow early diagnosis
      of ICMN and subsequent treatment with bypass surgery. On the other hand, advanced
      cases are not suitable for bypass surgery but should be given the benefit of an
      extensive clinical workup to assess the possibility of benefit of surgical over
      medical treatment. Of interest is the fact that the patient's father had an acute
      dissection at the age of 42, involving, however, the aorta, indicating possibly
      some genetic link.

PMID- 10064358
TI  - Does activated neutrophil depletion on bypass by leukocyte filtration reduce
      myocardial damage? A preliminary report.
AB  - An important factor in the production of myocardial damage following
      cardiopulmonary bypass in the creation of oxygen derived free radicals. Few
      sources for these radicals have been identified but experimentally activated
      neutrophils are known to release free radical which contribute to myocyte
      necrosis. The aim of this pilot study was to identify whether, by depleting
      patients of leukocytes and particularly neutrophils on bypass, a better degree of
      myocardial protection could be observed using specific identifiers of myocardial
      damage. Ten patients undergoing urgent coronary artery bypass for unstable angina
      with impaired left ventricular function were leuko-depleted using a PALL medical
      leukocyte filter in the extra corporeal circulation together with leukocyte
      depletion of all transfused blood. A similar group of matched controls had only
      an arterial line filter without leukodepletion. All patients were operated by one
      surgeon using identical techniques of intermittent cross clamping and
      fibrillation at moderate hypothermia. Full blood count, Glutathione, Troponin T
      and CPK/MB were measured before, during and at identified intervals up to 72 hour
      after bypass. Preliminary results show little change in the total leukocyte count
      but the Troponin T and CPK/MB values were lower in the filtered group than in the
      control group and an increased level of total Glutathione in the filter group
      showed that there was less oxidated stress on the myocardium. Currently this
      filter is an expensive addition to bypass surgery but these preliminary results
      suggest that activated neutrophil depletion on bypass may be of benefit to
      patients with unstable angina, impending myocardial necrosis and low ejection
      fraction.

PMID- 10064359
TI  - Intraoperative monitoring of the potassium-activity and pH- value on the
      myocardial surface during coronary bypass surgery.
AB  - INTRODUCTION: Ischemic periods very often occur a dysfunction of the heart. In
      this series the intraoperative changes of potassium-activity and pH- value on the
      heart undergoing cardioplegic induced cardiac arrest were studied. Furthermore,
      the sensitivity of the system in diagnostic fields of ischemic periods and
      reperfusion damages were investigated. METHODS: In eight patients (7 male and 1
      female pts.) undergoing elective cardiosurgical procedures (aortocoronary bypass
      grafts) the ion activity of potassium and hydrogen ions were monitored on the
      heart, intraoperatively. By ion-selective electrodes the superficial cardiac ion
      activities were evaluated on definitive time periods on the left (LV) and right
      ventricle (RV). RESULTS: Preliminary results suggest: In the reperfusion-period
      different pH-values result on the ventricles. In the end of reperfusion the pH
      values return to the starting points. Though the evaluated parameters are too
      alcaline in comparison to physiological intervals. The time course of epicardial
      potassium-concentrations is not different between the RV and LV. Initially, only
      low concentrations were found during perfusion and reperfusion, in the last
      interval of reperfusion period an increase of potassium on both ventricles were
      evaluated. In the end of the operations the superficial ion concentrations
      approximate to the values evaluated at the starting points. CONCLUSION: These
      results suggests, that the dynamics of ion-exchange-processes in the myocardium
      can be monitored with the help of ion-selective probes. This new technique opens
      new strategies in the qualitative check-up of myocardial protective procedures
      during cardioplegic cardiac arrest.

PMID- 10064360
TI  - Serum beta-2-microglobulin (beta-2-M) levels in heart transplant patients (HTP).
AB  - The present paper aim to answer following questions: 1. What is serum beta-2-M
      levels in HTP? 2. Does significant correlations between serum beta-2-M levels and
      serum creatinine levels or creatinine clearance (inulin clearance) exit? 3. Does
      any significant correlation between serum beta-2-M levels and blood cyclosporine
      A concentration exit? Three groups of subjects were studied. The first group
      consisted of 33 heart transplant patients (HTP), the second group consisted of 12
      patients with small decline kidney function, and the third one consisted of 36
      healthy subjects. In all examined subjects serum beta-2-M (RIA) creatinine,
      creatinine and inulin (steady state dosis method) clearance were assessed.
      CONCLUSION: 1. In observed HTP serum beta-2-M level is significantly higher then
      in controls and patients with small decline kidney function; 2. A significant
      correlation between kidney function and -2-M level in HTP as well as in other
      examined groups subjects exit; 3. Presence a significant positive correlation
      between serum beta-2-M level and blood cyclosporine A concentration suggest that
      beta-2-M level can be a good parametr to define cyclosporine A tubular toxicity.

PMID- 10064361
TI  - An original application of plasma expanders: heart-lung preservation.
AB  - The lack of an ideal heart-lung preservation solution is one of the principal
      factor that limits the wide spread of transplantation. The aim of this work was
      to investigate the efficacy of Haemaccel (HM) on isolated human pulmonary artery
      endothelial cells comparing its effects with those of University of Wisconsin
      (UWS). Subcultures of HPAEC were inoculated at the density of 5,000 cells per cm2
      in 9 cm2 well-plates. Cells were incubated with HM and UWS for 6 hrs at 10
      degrees C. Cellular viability was analysed by the total protein content
      (cytotoxicity index) and by the rate of protein synthesis (metabolic index). The
      results showed that HM and UWS did no show a significant differences in the
      toxicity when compared with the control; on the contrary, HM seems to determine a
      less inhibitory effect on cellular metabolism permitting a more rapid cellular
      metabolic recovery than UWS. Thus, HM appears to be more suitable for the
      preservation of isolated HPAEC than UWS.

PMID- 10064362
TI  - Cardiac myxoma: diagnostic approach, surgical treatment and follow-up. A twenty
      years experience.
AB  - At the University Department of Cardiovascular Surgery in Zagreb, Croatia, we
      treated 81 patients with primary intracardiac myxoma, in a period from January
      1975 to December 1994. There were 55 female and 26 male pts, in age from 1 month
      to 80 years, mean 46+/-15 years. Clinical manifestations varied from no symptoms
      and very poor or no clinical signs to various manifestations of chronic or acute
      congestive heart failure, syncope and arrhythmias with or without systemic
      findings such as high erythrocyte sedimentation rate, anaemia, leucocytosis,
      elevated gamma globulin, thrombocytopenia or low grade fever, as well as
      cerebrovascular accidents due to tumour embolization. Cardiac symptoms were
      predominant in 54 pts (66.6%) and cerebrovascular in 20 pts (24.7%). Seven pts
      (8.6%) were symptomless and discovered accidentally, mostly regarding on an
      unexplained heart murmur. In almost all the patients preoperative diagnosis of
      intracardiac myxoma was sufficiently established by echocardiography. The tumour
      was located in the left atrium in 62 pts (76.5%) and in the right atrium in 19
      pts (23.5%). Delay from the onset of symptoms to the diagnosis was 6 months in
      average (range 10 days to 25 months). The average waiting for the operation was 9
      days (range from 1 to 60 days). The echocardiographic diagnosis was confirmed
      during intraoperative examination followed by histological analysis. All pts
      underwent excision of myxoma using cardiopulmonary bypass with core and topical
      hypothermia and cold crystaloid cardioplegia. According to the additional
      preoperative and intraoperative findings, in 6 pts sinchronous mitral valve
      reconstruction, in 3 pts artificial mitral valve implantation and in 2 pts atrial
      wall reconstruction was performed. There was no perioperative mortality. After
      the operation, we could not evaluate all the patients long enough, mostly because
      of some paramedical circumstancies, such as war, migrations, etc. Twenty two pts
      undevent evaluation for at least 5 years after the operation. Among them there
      was no evidence of the tumour recurrence, 15 pts were asymptomatic and 7 had NYHA
      II class symptoms. For 17 pts with a left atrial myxoma preoperative and
      postoperative echocardiographic data were available for comparison, showing a
      significant reduction of the left atrial diameter (p<0.001) during the
      postoperative follow-up. Our data, presenting one of the biggest reports
      concerning cardiac myxomas, showed a broad spectrum of their clinical
      presentation, importance of echocardiography in diagnosing and postoperative
      follow-up and efficacy of a proper surgical intervention as a definite, curative
      therapy since there were no deaths and no significant cardiac dysfunction neither
      tumour reccurrence as well.

PMID- 10064363
TI  - Oxygen metabolism after cardiopulmonary bypass.
AB  - We hypothesized that the relationship between oxygen delivery (DO2) and oxygen
      consumption (VO2) in patients undergoing cardiopulmonary bypass (CPB) may differ
      from the normal physiologic state because of oxygen debts acquired during CPB.
      Blood gas analysis and hemodynamic parameters were repeatedly measured for
      determination of DO2 and VO2 in 40 patients undergoing CPB every 8 hours during
      the first 48 hours postoperatively. Twenty patients of acute myocardial
      infarction (AMI) also were studied in the same protocol as controls. 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/m2); VO2=121+0.0844 DO2
      (R=0.25, p=0.023). However, such supply-dependent oxygen consumption was not
      observed in the AMI patients. Perioperative parameters which had a significant
      relationship with oxygen extraction rate (VO2/DO2 x 100) were Hb concentration,
      cardiac index, systemic vascular resistance, age of the patients, duration of
      CPB, SaO2 and SvO2. These results suggest that patients undergoing CPB need a
      much higher oxygen supply to recover from the oxygen debt during open heart
      surgery.

PMID- 10064364
TI  - The long term results of treatment of heart myxomas with special attention to
      very rare myxoma of the right ventricle.
AB  - Fifteen patients with cardiac myxomas, 13 in the left atrium, one in the right
      atrium and one in the right ventricle were treated surgically during a 15 years
      period with no hospital and no late deaths. Left atrial myxomas revealed symptoms
      of obstruction to blood flow in 100%, symptoms of constitutional effects in 55%
      and thromboembolic events in 23%. Diagnosis of left atrial myxomas was made
      before operation in eleven patients by echocardiography or angiography or by both
      methods. In two patients diagnosis of left atrial myxoma was made incidentally
      during cardiac surgery for mitral stenosis. 8 left atrial myxomas originated from
      septum and 5 from the wall. Removal of the myxoma with the portion of the septum
      or the wall was performed in 11 patients and direct suture was satisfactory in 9
      cases. In 2 patients septum was repaired by pericardial patch. Septum was left
      intact in 2 patients. Follow-up period varied from 1/2 to 15 years, mean-above 8
      years. Estimation of late results was achieved by 2-D echocardiography in every
      patients. Results remain very good, patients are in the NYHA class 1,
      examinations revealed no recurrences. Special attention was paid to very rare
      case of huge right ventricular myxoma demonstrating wide infiltration of the
      endocardium and involvement of the tricuspid valve, which was completely
      destroyed. The technique of endocardial decortication was used for removal of the
      myxoma and tricuspid valve had to be replaced. Three months after operation
      extreme obstruction of the artificial valve was recognized. During second
      operation valve was cleaned from the thrombus but also fragments of the myxoma
      probably left during first operation were removed by wider technique of
      endocardial decortication. Results after 15 years remains very good. Right
      ventricular myxoma being on the border of operability needs more aggressive
      technique than simple removing.

PMID- 10064365
TI  - Intra-atrial myxomas, clinical-pathologic correlation based on two case studies
      including historical review.
AB  - The two cases of left-sided myxomas are reported with both patients having had
      uneventful cardiac surgery. One patient had an uneventful recovery and is doing
      well, whereas the second patient (female) had a complicating cerebrovascular
      accident. This patient was thought to have myxoma embolization; however,
      histopathologic verification could not be obtained. This latter patient had of
      course a higher risk of developing thromboembolization, due to the concomitant
      valve surgery procedure. The clinical, operative and pathologic studies confirm
      the lesions as primary myxomas and support and amplify the diagnostic concept of
      those lesions being of neoplastic nature, and countermand the previously commonly
      held concept of the thrombotic nature of myxomas. The nature of the myxoma is the
      primitive mesenchymal vasoformative cells of the atrial subendocardium, which is
      equivalent to the subendocardial cushion cell.

PMID- 10064366
TI  - Surgical treatment of atrial septal aneurysm.
AB  - The atrial septal aneurysm (ASA) is a morphologic abnormality known to cause
      peripheral and pulmonary embolism. 28-52% patients with ASA have embolic events.
      However ASA -- with no other concomittant cardiac patology has rarely been
      reported as the indication for open heart surgery. In this work, five cases of
      patients operated for ASA are presented. Embolic complications with cerebral
      symptoms were presented in three cases. The diagnosis of ASA was established with
      the use of transesophageal echocardiography. The surgical correction of the
      defect was performed in extracorporeal circulation. The aneurysmal part of
      interatrial septum was excised and replaced with a pericardial patch. The
      postoperative course was uneventful. The patients have no new embolic events
      during the follow up period of one year.

PMID- 10064367
TI  - The use of biocompound-grafts together with varicose veins. First clinical
      experience.
AB  - Complete revascularisation of patients with multivessel disease and inadequate
      veins is unsatisfactory despite the more frequent use of different arterial
      conduits. The lack of an accurate vascular prosthesis in coronary artery surgery
      forces to use in a certain number of patients varicose or ectatic veins. In these
      cases, an ultraflexible metal mesh tube is placed intraoperatively with the aid
      of an application set outside the harvested vein and the two joined with fibrin
      glue (=biocompound-graft). It reduces the graft diameter and improves the
      hemodynamic properties of the graft. In 18 patients with no alternative graft, 43
      biocompound-bypasses were implanted. The total number of implanted bypasses is 58
      (mean 3.2+/-1.0). At hospital dismission 41 of 43 biocompound-bypasses are open.
      One patient died 2 months after the operation. At follow-up (3.9+/-4.0 months),
      16 patients are at NYHA stage I or II, one patient at stage III. The first
      angiographic control in one patient shows all bypasses patent. First analysis of
      the results encourages continuous use of the biocompound-graft. The biocompound
      graft offers the surgeon the possibility of using varicose-ectatic veins if
      alternative bypasses are not available. Moreover, there is experimental evidence
      of reduced intimal hyperplasia when mechanical unloading of the vein-wall tension
      is performed.

PMID- 10064368
TI  - Thoracoscopic surgery in Brazil. An overview.
AB  - The Video Assisted Thoracic Surgery (VATS) was introduced in Brazil in 1992 by
      Losso, Ghefter and Imaeda. Since its advent up to November 1994, 488 patients
      have been submitted to 497 VATS procedures in four Medical Centers of Sao Paulo
      city. The indications for the procedures were: lung diseases in 244 patients
      (50%), pleural disease in 155 patients (31.7%), thoracic traumas in 42 patients
      (8.6%), mediastinal diseases in 35 patients (7.1%), cardiovascular diseases in 7
      patients (1.4%), chest wall diseases in 3 patients (0.6%) and esophageal diseases
      in 2 patients (0.4%). In the group of lung disease the most commonly used
      procedures were the lung biopsy in order to diagnose diffuse pulmonary disease
      and the indeterminate solitary nodule resection. Among the occurrences of pleural
      diseases, the most commonly used procedures were the pleurodesis with talc (talc
      poudrage) for the treatment of recurrent pleural effusion, the driven pleura
      biopsy and debridment or decortication of trapped lung in cases of pleural
      empyema. Concerning the mediastinal diseases, the pathology which was most
      frequently treated by VATS was the recurrent pericardic effusion through partial
      pericardiectomy. Among the patients presenting chest traumatic diseases, the VATS
      was used to explore thoracoabdominal penetrating injuries, to control bleeding,
      to remove clotted hemothorax, to suture diaphragm lesions and to remove
      intrapleural foreign bodies. Out of 497 procedures, there were 28 convertions to
      thoracotomy (5.7%) and two deaths occurred all over the cases. The complications,
      limitations and growth related to this method as well as a future overview of the
      VATS in Brazil will be presented.

PMID- 10064369
TI  - Neck and brain transitory vascular compression causing neurological
      complications. Results of surgical treatment on 1,300 patients.
AB  - In this brief article we describe the role of compression of the vertebral
      subclavian arteries, internal mammary, internal carotid arteries, brachial plexus
      and coiling and kinking of the vertebral and basilar arteries, the faulty
      irrigation of blood supply and oxygen of the cerebellum and basal ganglia of the
      brain. Among the effects are: a decrease in the secretion of dopamine at the
      level of the putamen, which produces the symptoms of Parkinson's disease, and
      chorea due to chronic transitory faulty blood supply and oxygen to the caudate
      nucleus, ballism by hypoxia at the level of subthalamic nuclei and athetosis in
      the lenticular nucleus. This compression is caused by the anterior scalene
      muscles and the cervical ribs at the level of the vertebrae C6-C7; by the
      sternocleidomastoid at the level of the cervical atlas; and coiling and kinking
      of the vertebral, basilar and the internal carotid arteries. The decreased blood
      supply to the cerebellum and basal ganglia is the cause of the Cerebellar
      Thoracic Outlet Syndrome (CTOS) and its neurological complications, among which
      are ipsilateral paralysis, Parkinson disease and others. We are presently engaged
      in several studies to widen our understanding of this phenomenon.

PMID- 10064370
TI  - Unusual indications for thoracoscopy.
AB  - Thoracoscopy has been utilized in a number of patients with unusual or difficult
      problems which were not resolved with standard thoracic techniques. These
      problems have been grouped in: infectious, tumour, iatrogenic and others.
      Personal experience and a survey of the literature on the subject show that
      thoracoscopy may be an ideal approach in many cases.

PMID- 10064371
TI  - Mesh insertion as an aid for pleurodesis.
AB  - With the application of video-assisted thoracic surgery (VATS) for the treatment
      of pneumothorax, there has been an increase in the failure rate of treatment
      because of inadequate pleurodesis. We sought to determine whether mesh insertion
      into the pleural cavity with or without pleural abrasion results in predictable
      pleurodesis appropriate for clinical trial as an adjunct to VATS treatment of
      pneumothorax. There have been no prior studies on the use of absorbable or
      nonabsorbable mesh in the thoracic cavity. The effects of intra-thoracic
      absorbable polyglactin (Vicryl) and non-absorbable polypropylene (Marlex) mesh
      were studied in rats. Polyglactin without abrasion caused filmy adhesions in 5/5,
      1/7, and 0/5 rats studied at 1, 2, and 3 months. Polypropylene incites an
      extensive and dense pleural reaction not suitable for clinical use becaues it
      induces a fibrothorax. Pleural abrasion alone caused variable adhesions studied
      at 3-4 months (4/6 none, 1/6 filmy, 1/6 firm). Polyglactin plus pleural abrasion
      resulted in appropriate firm adhesions in 7/8 rats studied at 3-4 months with 1/8
      showing filmy adhesions. Polyglactin alone results in transient filmy adhesions.
      Pleural abrasion alone results in inadequate pleural symphysis. However, when
      absorbable mesh insertion is coupled with pleural abrasion, appropriate
      pleurodesis is predictably achieved. Clinical application of polyglactin mesh
      insertion with pleural abrasion as an adjunct in the VATS treatment of
      pneumothorax has begun and has been successful.

PMID- 10064372
TI  - Mediastinoscopy, thoracoscopy and left anterior mediastinotomy in the diagnosis
      of N2 non small cell lung cancer.
AB  - The preoperative diagnosis of the involvement of the N2 lymph nodes is very
      important in patients with NSCLC for the most appropriate treatment. The
      classical diagnostic techniques for mediastinal exploration, mediastinoscopy and
      left anterior mediastinotomy, have been recently integrated by videothoracoscopy.
      FromJanuary 1993 to April 1994 186 patients with NSCLC suitable for surgery, were
      observed in our Department. 18 patients (9%) had CT evidence of N2 disease. In 10
      cases the sites of the nodal enlargement were the right paratracheal station (#2
      according to Naruke) and the right tracheobronchial station (#4), in 4 the
      subcarinal station (#7), in 2 the subaortic (#5) and in the remaining 2 cases the
      paraaortic station (#6). 14 mediastinoscopies were performed to investigate the
      stations 2,4 and 7,2 videothoracoscopies for station 5 and 2 left anterior
      mediastinotomies for station 6. The histological diagnosis was obtained in all
      cases without intraoperative or postoperative complications. Because the sequence
      chemotherapy-surgery seems to obtain the best results in the treatment of N2
      disease the preoperative diagnosis of nodal involvement is of outstanding
      importance. Until recently mediastinoscopy and anterior left mediastinotomy were
      considered the standard techniques to explore mediastinum, now also
      videothoracoscopy has been introduced. In our experience, the integration of all
      the above techniques allowed a complete study of each suspect N2 site.
      Particularly the videothoracoscopy is very useful to safely biopsy under direct
      vision the aortic window lymph nodes.

PMID- 10064373
TI  - Autologous bone transplant after sternal resection.
AB  - Two patients underwent subtotal sternal resection for tumors of the sternum.
      Anatomical and functional reconstruction was performed with bone fragments
      harvested from the internal lamina of both iliac wings. There were no infections
      and no instabilities. Late postoperative follow-up included CT-scan of the thorax
      and pulmonary function testing, which was not compromised. We conclude that this
      surgical approach is very efficient in regard to function and chest wall
      stability.

PMID- 10064374
TI  - Wound infection after median sternotomy during the war in Croatia.
AB  - From 1990 to 1994 at Clinical Hospital Center, Zagreb, 1904 median sternotomies
      were performed for cardiac operations. Patients shared the same intensive care
      unit (ICU) with the wounded persons, admitted to the hospital from battlefield.
      Infection developed in 124 patients, an incidence of 6.51%. Methicillin resistant
      Staphylococcus aureus (MRSA) was isolated from 90, methicillin resistant
      Staphylococcus epidermidis (MRSE) from 19, and gram negative bacilli (GNB) from
      56 patients, Pseudomonas aeruginosa in 2, and Clostridium pneumoniae in 1 case.
      Ninety-six patients (5.04%) developed superficial localized infection of
      subcutaneous tissues and they were treated with frequent dressing changes with
      antibiotic-soaked gauze in combination with systemic antibiotics. Twenty-eight
      patients (1.47%) developed mediastinitis and sternal dehiscence. They were
      treated by operative debridement followed by reclosure of the sternum with
      continuous antibiotic irrigation. We obtained satisfactory results with our
      method of closure of sternum which is a modification of Robicsek's technique.
      Nine of them required further operation. In seven cases we performed muscle flaps
      and in two omentoplasty. One hundred and twenty patients were discharged in
      satisfactory condition. The uncontrolled mediastinal sepsis caused death in 4
      patients. Higher infection rate after median sternotomy during 1991 and 1992
      could be possibly explained with the war circumstances in Croatia, and especially
      with MRSA strain becoming endemic in surgical ICU.

PMID- 10064375
TI  - Reduction of blood ethanol levels by the gamma-hydroxybutyric acid receptor
      antagonist, NCS-382.
AB  - The present study demonstrates that the gamma-hydroxybutyric acid receptor
      antagonist, NCS-382, markedly reduces blood ethanol levels (BELs) in rats when
      ethanol is administered via the intragastric route, whereas it is completely
      ineffective when ethanol is injected IP. The reducing effect of NCS-382 on BELs
      is likely due to a lessened absorption of ethanol from the gastrointestinal
      tract.

PMID- 10064376
TI  - Dose- and time-dependent effects of ethanol on plasma antioxidant system in rat.
AB  - This study investigates the dose- as well as time-dependent effects of ethanol
      ingestion on antioxidant system and lipid peroxidation in plasma of the rat. The
      plasma ethanol concentrations were 154+/-18, 231+/-53, and 268+/-49 mg/dl 1 h
      after oral ethanol doses of 2, 4, and 6 g/kg, respectively. Superoxide dismutase
      (SOD) (71%, 56%, and 41 % of control) and glutathione reductase (GR) (71%, 66%,
      and 55% of control) activity in plasma were significantly decreased in a dose
      dependent manner. Catalase (CAT)/SOD and glutathione peroxidase (GSH-Px)/SOD
      ratios were significantly increased whereas GR/GSH-Px ratio was significantly
      decreased with increasing dose of ethanol. In a time course study, plasma ethanol
      concentrations were 177+/-9.7, 143+/-11, 99+/-17, and 26+/-11 mg/dl at 1.5, 2, 4,
      and 6 h after an oral dose (4 g/kg) of ethanol in rat indicating time-dependent
      elimination of ethanol. Plasma SOD and GSH-Px activity significantly increased 4
      6 h whereas GR activity significantly decreased 2-4 h after ethanol ingestion.
      The ratio of GR/GSH-Px and the ratio of reduced glutathione (GSH) to oxidized
      glutathione (GSSG) in plasma decreased at 1.5-6 h after ethanol ingestion. Plasma
      malondialdehyde (MDA) levels significantly elevated with respect to an increase
      in time after ethanol ingestion, indicating time-dependent augmentation of lipid
      peroxidation. The data indicate that ethanol ingestion perturbs the plasma
      antioxidant system in a dose- and time-dependent manner. The significant changes
      in the ratios of CAT/SOD, GSH-Px/SOD, GR/GSH-Px, and GSH/GSSG in plasma may be
      used as an index of alcohol-induced oxidative stress.

PMID- 10064377
TI  - Does the short variant of the serotonin transporter linked polymorphic region
      constitute a marker of alcohol dependence?
AB  - The serotonin (5-hydroxytryptamine: 5-HT) system has been thought to play an
      important role in several steps of alcohol craving. A number of studies,
      including our own, have reported that alcohol dependence is associated with
      dysfunction of 5-HT transmission. Pharmacological and clinical studies have shown
      that the 5-HT transporter (5-HTT) and the 5-HT1A receptor appear to be candidate
      loci for the aetiology of alcohol dependence. We have analysed the presence of
      different 5-HTT and 5-HT1A variants in 104 alcohol-dependent patients and 38
      controls for a possible association with alcohol dependence. In alcohol-dependent
      patients, we found a high frequency of the S allele of 5-HTTLPR (45.5% vs. 29%,
      chi2 = 6.33, p = 0.0081). No other significant differences were observed between
      the two populations for other polymorphisms. These results provide, for the first
      time, preliminary evidence that alcohol abuse disorders are associated with a
      genetic variant for 5-HT transmission. It might be possible to use this detection
      of the "S" allele as a clinical tool for pathology diagnosis and to advise
      recovering alcoholics and it could represent an aid to the prevention of relapse.
      Therapeutic actions could be envisaged to use this genotyping to help select the
      best therapeutic strategy.

PMID- 10064378
TI  - Effects of lifelong ethanol consumption on rat sympathetic neurons.
AB  - In this experiment we studied the effects of aging and lifelong ethanol
      consumption on rat peripheral sympathetic neurons. The aim was to find out the
      possible differences in the vulnerability to ethanol-induced neuronal
      degeneration between rats of both genders, or between the alcohol-avoiding (ANA)
      and the alcohol-preferring (AA) lines of rat. The superior cervical ganglia (SCG)
      of 40 male and 41 female AA and ANA rats were analyzed. The ethanol-exposed
      groups had 12% ethanol as the only available fluid from 3 to 24 months of age.
      The young (3 months) and old (24 months) control groups had water instead. SCG
      neuronal density, volume, and total neuron number were measured by unbiased
      morphometric methods. No gender difference was seen in either the volume of the
      SCG or in the SCG neuron number. The volume of the ganglion was significantly
      increased with age, but the total neuron number did not change. Neuronal density
      was significantly decreased with age, but lifelong ethanol consumption induced no
      further decrease. SCG neuron number in the ethanol-exposed groups did not differ
      from the age-matched or young control groups, but a significant negative
      correlation (r = -0.70, p<0.01) was seen between individual ethanol consumption
      and the number of SCG neurons in the female rats. The amount of lipopigment in
      the SCG was increased in the ethanol-exposed male rats. These results suggest
      that the peripheral sympathetic neurons are rather resistant to ethanol-induced
      degeneration, and that no major gender or line differences exist in this respect.

PMID- 10064379
TI  - Blood and urinary levels of ethanol, acetaldehyde, and C4 compounds such as
      diacetyl, acetoin, and 2,3-butanediol in normal male students after ethanol
      ingestion.
AB  - Aldehyde dehydrogenase (ALDH) isozyme 2 genes were determined in 15 students. Of
      these subjects, five healthy male students were administered 0.4 kg/kg ethanol.
      One subject was defective in aldehyde dehydrogenase 2 (ALDH2), two had normal
      ALDH2, and the other two were hetero type. After the intake of alcohol, the
      concentration of ethanol, acetaldehyde, and C4 compounds in blood and urine were
      determined. The student with the inactive form of ALDH2 was flushed and his
      levels of 2,3-butanediol and acetaldehyde in blood and urine were found to be the
      highest.

PMID- 10064380
TI  - Electrophysiology of hippocampal CA1 neurons after prenatal ethanol exposure.
AB  - In the present study, we examined the longitudinal effects of prenatal ethanol
      exposure on the electrophysiological characteristics of CA1 neurons in
      hippocampal slices. Hippocampal slices were obtained from young (25-32-day old)
      and adult (63-77-day old) male offspring of rats given one of four treatments
      during gestation. Three groups of pregnant rats were orally intubated with 0, 4,
      or 6 g/kg ethanol on gestational days 8-20. Caloric intake for the 0-
      (nutritional control) and 4-g/kg groups was yoked to that of the 6 g/kg group. A
      fourth group (untreated control) was not intubated, and was given ad lib access
      to food. Long-term potentiation and paired-pulse inhibition were unaffected by
      prenatal ethanol exposure in young and adult rats; however, slices taken from the
      young 6 g/kg ethanol group displayed a significantly lower maximal CA1 population
      spike amplitude evoked by Schaffer collateral stimulation as compared to young
      controls. This difference was not observed in adult animals. These data suggest
      that some aspects of hippocampal physiology are negatively affected in young rats
      as a result of prenatal ethanol exposure, but this effect reverses as the animal
      matures.

PMID- 10064381
TI  - Dose-response relationships between drinking and serum tests in Japanese men aged
      40-59 years.
AB  - Alcohol intake per Japanese adult has been increasing year by year. To show
      biological effects of drinking, the dose-response relationships between alcohol
      use and serum indices were analyzed in 5919 Japanese men aged 40-59 years. The
      subjects were classified into nine groups: a nondrinking (ND, n = 1827) group and
      eight drinking (1D-8D) groups, by self-reported drinking habit. The 1D (the
      lightest drinking, n = 699), 5D (n = 942), and 8D (the heaviest drinking, n = 46)
      groups consumed alcohol less than 30 g per week, 25-30 g alcohol per day, and 100
      g alcohol per day or more, respectively. Ten serum indices, total cholesterol,
      HDL cholesterol, triglyceride, total/HDL cholesterol ratio, LDL cholesterol,
      gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine
      aminotransferase, glucose, and uric acid, were used. The dose-response analysis
      was statistically controlled for age, body mass index, smoking, and habitual
      exercise, and showed that drinking, even a small amount of alcohol, always had
      both beneficial and adverse effects on humans. However, alcohol less than 30 g
      per day may be tolerable for middle-aged Japanese men, because it improved serum
      lipids profile but did not induce apparent liver cell damage, hyperglycemia, or
      hyperuricemia.

PMID- 10064382
TI  - Operant ethanol self-administration after nicotine treatment and withdrawal.
AB  - The effects of chronic intermittent administration of nicotine (NIC) and
      withdrawal on operant ethanol (EtOH) self-administration were tested in Long
      Evans rats (n = 8). EtOH self-administration (10% v/v, Fixed Ratio 4
      reinforcement schedule) was induced by the sucrose-substitution procedure. Then
      the animals were divided into two groups of four rats matched on EtOH self
      administration and the locomotor activity following an injection of NIC (0.35
      mg/kg, SC) or saline was measured. The groups then received 9 days of injection
      of either NIC (0.35 mg/kg) or saline and then motor activity was retested using
      the initial NIC dose. This was followed by 17 days of NIC injections (0.6 mg/kg)
      or saline injections. A final locomotor test using the higher NIC dose was then
      conducted. The initial acute administration of NIC had no effect on motor
      activity compared to saline (measured by the number of horizontal movements).
      However, after the repeated treatment, the group of animals injected chronically
      and acutely with NIC showed motor activation in comparison with the animals
      injected chronically with saline and injected acutely with NIC only on the days
      of activity testing. At the end of the chronic NIC treatment, operant EtOH self
      administration was not changed. However, 6 days after the NIC injections were
      concluded, a change in the pattern of responding for EtOH was observed in the NIC
      group, showing a decrease in the mean rate of responding during the first half of
      the operant self-administration session. When both groups were again tested for
      locomotor activity at the end of the operant self-administration experiment, the
      increased motor activity in the NIC group was still observed. The results suggest
      that alterations in the nicotinic system may affect EtOH self-administration, but
      this appears to be only modulatory, even with a significant change in locomotor
      response to NIC following chronic NIC administration.

PMID- 10064383
TI  - P300, alcoholism heritability, and stimulus modality.
AB  - The P300 event-related brain potential (ERP) was elicited with auditory and
      visual stimuli from members of 13 families who were at high risk (HR) for
      alcoholism (father diagnosed as alcoholic) and 13 families at low risk (LR) for
      alcoholism. Each family consisted of a father, mother, and at least two
      biological children. The intrafamily member correlations (father vs. child,
      mother vs. child, child vs. child) for P300 amplitude were obtained for 15
      electrode sites. P300 amplitude from auditory stimuli was not correlated among HR
      family members, but was positively correlated among LR family members. P300
      amplitude from visual stimuli was positively correlated among both HR and LR
      family members. When taken in conjunction with previous findings, the present
      results suggest that P300 amplitude from auditory stimuli may not be as reliable
      as ERPs from visual stimuli for the assessment of alcoholism heritability.

PMID- 10064384
TI  - Different behavioral patterns related to alcohol use in rodents: a factor
      analysis.
AB  - To estimate genetic correlations among behavioral measures from explorative
      crossmaze, inescapable slip funnel, as well as from drinking tests, the data from
      five pairs of high/low alcohol drinking rat (AA/ANA, P/NP, HAD1/LAD1, HAD2/LAD2,
      HIGH-IPH/LOW-IPH) and from three pairs of mouse (B10.AKM/B10.A(4R), HD/LD,
      Small_Brain/ Large_Brain) lines were evaluated by the use of principal component
      analysis. The analysis yielded a two-factor solution explaining 71.8% of total
      variability. Both the factors had high positive loadings on alcohol drinking. The
      first factor had sufficient positive loadings on latency of crossmaze exploration
      and total time of slip funnel immobility, whereas, there was a negative loading
      on slip funnel avoidance. The second factor had positive loadings on efficacy of
      crossmaze exploration and slip funnel escape attempts, whereas there was a
      negative loading on slip funnel immobility. The number of defecations in the
      crossmaze, time in open arms of the elevated plus-maze, time immobile during the
      forced-swim test, as well as intake of a saccharin solution, additionally
      available for a lesser number of the lines, were studied for correlations with
      the factor scores. The first factor of "alcohol drive with timidity and meekness"
      exhibited positive relation to saccharin intake. Time in the open arms of the
      elevated plus-maze showed significant negative correlation with a latency of
      crossmaze exploration. The second factor of "alcohol drive with novelty seeking
      and persistence" showed a negative link to crossmaze defecations and forced-swim
      immobility.

PMID- 10064385
TI  - The antioxidants vitamin E and beta-carotene protect against ethanol-induced
      neurotoxicity in embryonic rat hippocampal cultures.
AB  - Fetal alcohol syndrome is characterized by numerous nervous system anomalies with
      the developing hippocampus being highly vulnerable. Other conditions can result
      from maternal ethanol consumption including oxidative stress. Critical
      antioxidants, such as vitamin E, can be decreased and antioxidative defenses
      altered. Gestational day 18 rat hippocampal cultures were exposed to ethanol
      ranging from 400 to 2400 mg/dl (16 h). MTT assays assessed neurotoxicity.
      Viability was decreased dose dependently. Supplementation with vitamin E or beta
      carotene afforded neuroprotection against all ethanol concentrations. Vitamin E
      completely ameliorated neuronal loss following 400 and 800 mg/dl ethanol. Vitamin
      E increased survival to 95%, 79%, 66%, and 75% during 1600, 1800, and 2000 and
      2400 mg/dl ethanol compared to nonethanol treatment. Vitamin E increased
      viability by 38%, 23%, 12%, and 29% at 1600, 1800, 2000, and 2400 mg/dl compared
      to non-vitamin E-supplemented, ethanol treatment. beta-Carotene completely
      ameliorated cell loss from 400 mg/dl ethanol and increased survival by 18% at
      1600 mg/dl and 12% at 2000 mg/dl. This study demonstrates in vitro antioxidative
      neuroprotection against developmental ethanol exposure and suggests that
      nutritional therapies incorporating antioxidants may help protect against
      deleterious fetal effects from maternal alcohol abuse.

PMID- 10064386
TI  - The investigation of sudden cardiac death.
AB  - Pathologists are faced with an increasing complexity in the cardiac diseases that
      cause sudden natural death in the absence of coronary artery disease. A
      significant proportion of such natural sudden deaths are due to familial heart
      muscle disease (cardiomyopathy). The phenotypic characteristics of both
      hypertrophic cardiomyopathy and arrythmogenic right ventricular dysplasia are
      wider than previously thought and the hearts may be very close to normal on naked
      eye examination. Detailed histology of the myocardium is needed to identify such
      cases. Up to 200 sudden deaths a year in England occur in young, apparently fit
      individuals in whom toxicology and detailed examination of the heart for
      structural abnormalities is negative. Genetic defects in ion channels (long QT
      interval) are now known to be one cause of this phenomenon. In investigating a
      case of sudden death without cause, a study of the family -- if they wish it --
      may be helpful in arriving at a cause.

PMID- 10064387
TI  - Endometrial apoptosis in patients with dysfunctional uterine bleeding.
AB  - AIMS: To assess glandular apoptosis in the zona functionalis of proliferative
      phase endometrium in normal individuals and in patients with dysfunctional
      uterine bleeding (DUB). METHODS AND RESULTS: Routinely processed, haematoxylin
      and eosin-stained endometrial biopsies were assessed in 26 patients with
      symptomatic menstrual abnormality, mainly menorrhagia, and in 24 controls. All
      biopsies were in the proliferative phase and had been reported as within normal
      limits and consistent with the menstrual cycle dates provided. Apoptotic and
      mitotic figures were counted in a minimum of 100 transversely sectioned
      endometrial glands in all cases. In 16 biopsies (12 DUB and four controls)
      apoptosis was further assessed using the in situ terminal deoxynucleotidyl
      transferase-mediated 2'-deoxyuridine-5'-triphosphate (dUTP) nick-end labelling
      (TUNEL) method. Apoptotic figures were identified in most control biopsies
      averaging 5.6/100 glands, and were significantly increased in biopsies from
      patients with DUB averaging 13.9/100 glands. There was no difference in mitotic
      figure counts. Apoptoses tended to be clustered within adjacent glands in both
      groups and individual glands exhibited both mitotic and apoptotic activity.
      Application of the TUNEL method gave broad agreement with morphological
      assessment although approximately 20-25% of typical apoptotic figures were not
      labelled. CONCLUSIONS: Endometrial glandular apoptosis is present in most normal
      proliferative phase biopsies and appears increased in some cases of DUB. The
      significance of this finding is not known but increased apoptosis may serve as a
      morphological marker of abnormal endometrial development in otherwise normal
      biopsy specimens.

PMID- 10064388
TI  - Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive
      ductal carcinomas: a correlation with other biological parameters.
AB  - AIM: BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator
      of the cell cycle and may be an active inhibitor of neoplastic progression.
      Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast
      cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have
      been identified in breast cancer lines and in sporadic cases of breast cancer
      tissues. The expression of BRCA1 in large series of variously differentiated
      breast carcinomas with correlation with other biological parameters has not been
      clarified. METHODS AND RESULTS: The BRCA1 expression in normal breast tissue (n =
      15) and in sporadic cases of invasive ductal carcinoma (n=108) was determined
      using immunohistochemistry. BRCA1 expression was correlated with other prognostic
      parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological
      grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively
      (100%) localized in the nuclei of normal ductal and lobular epithelia. However,
      this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of
      nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high
      histological grade (P<0.025) and bcl-2-negative tumours (P<0.05) and frequently
      in ER-negative tumours. CONCLUSION: BRCA1 nuclear expression could be considered
      to represent the normal or physiological phenotype. Complete loss of BRCA1
      nuclear expression in breast cancer and its correlation with other poor
      prognostic markers suggest that BRCA1 expression may play an important role in
      the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1
      phenotype may therefore provide an additional prognostic parameter for breast
      cancer.

PMID- 10064389
TI  - CA125 and thyroglobulin staining in papillary carcinomas of thyroid and ovarian
      origin is not completely specific for site of origin.
AB  - AIMS: A 70-year-old woman presented with metastatic psammoma body-rich papillary
      carcinoma in a supraclavicular lymph node. No primary site was evident. The
      tumour showed strong staining for CA125 and weak staining for thyroglobulin.
      Prompted by this case we aimed to assess the reliability of immunostaining for
      CA125 and thyroglobulin in making the distinction between thyroid and ovarian
      papillary carcinoma. METHODS AND RESULTS: Nine papillary carcinomas of the
      thyroid and 17 serous papillary carcinomas of the ovary were stained for CA125
      and thyroglobulin, as well as CAM 5.2, LP 34, carcinoembryonic antigen (CEA),
      S100 and diastase/periodic acid-Schiff. Nine of nine thyroid carcinomas stained
      for thyroglobulin; in addition CA125 was positive in four of nine. Normal
      surrounding thyroid also showed some reaction. Seventeen of 17 ovarian serous
      carcinomas were positive for CA125; in addition one case showed moderately strong
      staining for thyroglobulin. Mucin stains were positive in 14/17 ovarian serous
      carcinomas, but negative in all thyroid carcinomas. The other antibodies assessed
      showed no useful differences in staining frequency. CONCLUSION: Many cases of
      papillary carcinoma of the thyroid show CA125 staining, and this feature
      therefore has little positive predictive value for an ovarian origin. Occasional
      cases of ovarian papillary carcinoma may show staining for thyroglobulin, and
      this result should therefore be interpreted cautiously.

PMID- 10064390
TI  - The role of Helicobacter pylori in primary gastric MALT lymphoma.
AB  - AIMS: Helicobacter pylori has been claimed to be an important aetiological factor
      which raises the risk of mucosa-associated tissue lymphoid (MALT) lymphoma.
      However, some studies on gastric MALT lymphoma revealed a low rate of H. pylori
      infection suggesting that not all gastric lymphomas are related to H. pylori
      infection. The aim of this study was to verify the H. pylori infection frequency
      in a series of patients with primary gastric MALT lymphomas and to examine the
      relationship between H. pylori and the pathological features of those lymphomas.
      METHODS AND RESULTS: Thirty-one cases of resected gastric lymphoma were analysed:
      10 cases (32%) were low-grade MALT lymphomas and 21 cases (68%) were high-grade
      MALT lymphomas. Helicobacter pylori was found in only 18 of 31 (58%) cases.
      Helicobacter pylori infection was significantly correlated with the grade and
      depth of invasion of MALT lymphoma since 63% of superficial low-grade MALT
      lymphomas were positive for H. pylori compared with 38% of advanced high-grade
      MALT lymphomas (P = 0.02). CONCLUSION: We confirmed the relationship between H.
      pylori infection and a subset of gastric MALT lymphoma. Our results also showed
      that not all low- and high-grade gastric MALT lymphomas are H. pylori-dependent.
      This suggests that H. pylori infection may play a promoter role in the
      development of MALT lymphoma, but its presence is not mandatory for the
      progression of the lymphoma in view of its low frequency in advanced high-grade
      MALT lymphoma.

PMID- 10064391
TI  - Interobserver agreement in the assessment of gastritis reversibility after
      Helicobacter pylori eradication.
AB  - AIM: Our aim was to determine interobserver agreement in the application of the
      Sydney system to assess reversibility of gastritis after Helicobacter pylori
      eradication. METHODS AND RESULTS: Forty-three patients with a Helicobacter pylori
      positive duodenal ulcer disease were included in the study. All patients included
      had successful H. pylori eradication after different antimicrobial drug
      combinations. Biopsy samples were collected from antrum and body, according to
      the Sydney recommendations, before antimicrobial therapy, 2 months after and at
      yearly intervals during 2-4 years of follow up. Three pathologists, who were
      blind to clinical data, evaluated histological changes in 221 antral and 219 body
      specimens stained with haematoxylin and eosin and with Warthin Starry. The
      percentage of pairwise agreement, kappa and weighted kappa statistic were used.
      Agreement in recognizing the presence of H. pylori colonization of the gastric
      mucosa, activity of inflammation and intestinal metaplasia was over 90%.
      Agreement in recognizing chronic inflammation in the body and atrophy in the
      antrum was between 78 and 89% respectively. The kappa values were excellent (more
      than 0.75) for the grade of H. pylori in the body, good (between 0.50 and 0.75)
      for the grade of H. pylori in the antrum, grade of inflammatory activity and
      intestinal metaplasia in the antrum and moderate to good (0.38-0.53) for the
      grade of chronic inflammation. Kappa values were poor to good (from 0.17 to 0.57)
      only in evaluation of the grade of atrophy. CONCLUSION: Interobserver agreement
      in the application of the Sydney system to reversibility of gastritis after H.
      pylori was good. More strict criteria should be used for atrophy and to
      differentiate normal and mild chronic inflammation.

PMID- 10064392
TI  - Cell density of adrenomedullin-immunoreactive cells in the gastric endocrine
      cells decreases in antral atrophic gastritis.
AB  - AIMS: Adrenomedullin (AM) is a novel hypotensive and vasorelaxing peptide
      recently isolated from human phaeochromocytoma tissue, and is widely distributed
      in various organs. In this study we examined the localization of AM
      immunoreactive (IR) cells in the gastric mucosa and AM-IR cell density in antral
      atrophic gastritis. METHODS AND RESULTS: Gastric mucosal tissues were taken from
      the gastric body and antral mucosa of 52 patients (27 men, 25 women; mean age
      56.0 (range 20-86) years). Immunohistochemical analysis revealed that AM-IR cells
      were present in the pyloric glands, but not in the fundic glands, and that AM-IR
      cells were stained positively for chromogranin A and gastrin. The percentage of
      AM-IR cells vs chromogranin A- and gastrin-IR cells was 42 and 56%, respectively.
      The number of AM-IR cells decreased with the progression of severity of atrophic
      changes in the pyloric gland, and also of mononuclear cell infiltration. There
      was no correlation between the number of AM-IR cells and the degree of
      neutrophilic infiltration. Similar findings were also obtained for gastrin-IR
      cells. CONCLUSION: AM-IR cells are present in the endocrine cells including
      gastrin-IR cells in the pyloric glands. These results suggest that AM may
      contribute to gastrin secretion in the pyloric glands.

PMID- 10064393
TI  - Focal malakoplakia in chronic periapical periodontitis.
AB  - AIMS: Three cases of chronic periapical periodontitis including focal areas with
      malakoplakia changes are reported. METHODS AND RESULTS: These areas included both
      von Hansemann-type macrophages and periodic acid-Schiff-positive, iron- and
      calcium-containing concretions. Some concretions corresponded to spherules with a
      targetoid configuration, thus fitting the morphological criteria for classical
      Michaelis-Gutmann bodies. CONCLUSION: The vast majority of the cases of
      malakoplakia that have been reported in the literature corresponded to a
      characteristic, fairly homogeneous lesion, but a few instances of focal
      malakoplakia have been described in various chronic conditions. These
      considerations support the opinion that the local conditions for the production
      of Michaelis-Gutmann bodies may occur focally in diseases characterized by
      macrophage accumulation.

PMID- 10064394
TI  - Haemophilic arthropathy resembles degenerative rather than inflammatory joint
      disease.
AB  - AIMS: To investigate the pathogenetic mechanisms of haemophilic arthropathy (HA)
      by comparing end-stage arthropathy with osteoarthritis (OA; a degenerative joint
      disorder) and rheumatoid arthritis (RA; an inflammation-mediated joint disease).
      METHODS AND RESULTS: Cartilage and synovium from patients with HA (n=10), RA
      (n=8), OA (n=14) and normal control subjects (n=6) were examined morphologically,
      biochemically and histochemically. Cartilage in HA exhibited characteristics of
      degenerative joint disease (OA), as evidenced by morphological, histochemical
      (Safranin-O fast green-iron haematoxylin, Mankin grade) and biochemical
      (proteoglycan synthesis, glycosaminoglycan content and DNA content) changes,
      whereas synovium in HA showed characteristics of inflammation-mediated joint
      disease (RA), as evidenced by histochemical (inflammation, haematoxylin and eosin
      (H&E) and iron deposition, Perls' blue) and biochemical changes (interleukin (IL)
      1, IL-6, tumour necrosis factor (TNF)alpha and catabolic properties). CONCLUSION:
      Haemophilic arthropathy shows characteristics of both inflammatory and
      degenerative joint disease. On the basis of these results and published
      information, it appears that degenerative cartilage changes have a dominant role
      in HA and are augmented by relatively mild inflammation of the synovium.

PMID- 10064395
TI  - Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group
      Study.
AB  - AIMS: We have reviewed immunohistochemically 17 paediatric medulloblastomas in
      order to determine if correlations exist that might be useful in subclassifying
      these tumours. METHODS AND RESULTS: The patient group included 11 children who
      had died (mean survival 13 months) and six still alive (followed for up to 10
      years). Ten tumours were diffuse and six were nodular (one biopsy had only
      perivascular tumour). Of the 10 diffuse tumours, three were desmoplastic: of the
      six nodular tumours, all six were desmoplastic. All 17 tumours were synaptophysin
      reactive: three nodular tumours were glial fibrillary acidic protein (GFAP)
      reactive in the nodules (two of three S 100-reactive tumours were also GFAP
      reactive). MIB-1 labelling indices (LI) ranged from 5 to 80%. Six tumours
      exhibited at least 1% LI against Tp53 (Mab D07 and/or Mab 1801). Eight cases were
      100% bcl2-reactive with nine cases having an LI <80% ('low labelling'). All nine
      'low labelling' bcl2 cases were TP53 non-reactive; all six Tp53-reactive cases
      were bcl2 100% reactive. Six of 10 patients with diffuse medulloblastomas
      survived 18 months or less while four of 10 are alive up to 10 years. In
      contrast, five of six patients with nodular neoplasms died within 48 months of
      diagnosis with one patient followed up for less than 1 year. CONCLUSIONS:
      Immunohistochemistry is a useful adjunct in characterizing subsets of paediatric
      medulloblastomas and confirms that larger co-operative studies may be fruitful in
      identifying a prognostic utility of a combined histochemical/immunohistochemical
      analysis on these tumours.

PMID- 10064396
TI  - Diagnostic relevance of chromosomal in-situ hybridization in Merkel cell
      carcinoma: targeted interphase cytogenetic tumour analyses.
AB  - AIMS: To resolve the conflicting diagnoses of five pathologists (which included
      well-differentiated neuroendocrine carcinoma, malignant carcinoid,
      undifferentiated small-cell carcinoma, primitive neuroectodermal tumour,
      metastases of small-cell lung carcinoma (SCLC) and Merkel cell carcinoma (MCC)),
      and tumour-free lungs after necropsy, we investigated an alarmingly metastasizing
      MCC in a 32-year-old Caucasian man using chromosomal in-situ hybridization
      (CISH). Differences in incidence and course in males and females also prompted
      targeted analyses for chromosomes X and Y. The lesion was also analysed for p53
      gene mutations. METHODS AND RESULTS: Paraffin sections of the thorax, buccal
      lymph nodes and scalp tumours were stained with haematoxylin and eosin.
      Immunohistochemistry was performed with antibodies against pancytokeratin,
      keratin 20, neuron-specific enolase (NSE), chromogranin, neurofilaments and
      vimentin, among others. Sections (5-6 microm) of the tumours were analysed with
      alpha-satellite probes for chromosomes 1, 6, 7, 11, 12, 17, 18, X and Y using
      CrSH; and exons 5-9 of the p53 gene were examined by polymerase chain reaction
      and single strand conformation polymorphism (PCR-SSCP) methods. Although positive
      for pancytokeratin, keratin 20, chromogranin, NSE, synaptophysin and vimentin,
      the similarity in antigen profiles expressed by SCLC and MCC prevented a
      definitive tumour diagnosis. Chromosomal in-situ hybridization, however, revealed
      trisomies 1 and 11, two frequent aberrations in MCC, and trisomy 18. Moreover,
      71% of the tumour cells had two to three copies of X, whereas 98% of the cell
      nuclei in the hair follicles and normal epidermis (purported Merkel cell origins)
      displayed one X chromosome. No mutations were detected in the five exons of the
      p53 gene examined. CONCLUSIONS: Had CISH been performed earlier, treatment may
      have been tailored specifically to suit MCC, since MCC and SCLC have different
      therapeutic strategies. Finally, chromosome X may be of prognostic relevance in
      MCC, which apparently predominates in females and yet shows poorer prognosis in
      males, and hence be worthy of further investigation.

PMID- 10064397
TI  - Expression and function of BRCA1 and BRCA2 in familial and sporadic breast
      cancer.

PMID- 10064399
TI  - Electron microscopy for the fine needle aspiration of tumours.

PMID- 10064398
TI  - Prognostic comparison of three classifications for medullary carcinoma of the
      breast.

PMID- 10064400
TI  - Biotin inclusions: a potential pitfall in immunohistochemistry avoided.

PMID- 10064401
TI  - Myoid cells in the fibrosarcomatous variant of dermatofibrosarcoma protuberans.
      Are they neoplastic?

PMID- 10064402
TI  - Vascular myxolipoma (angiomyxolipoma) of subcutaneous tissue.

PMID- 10064403
TI  - Peritoneal rosetting microgranulomas in an incarcerated small bowel loop.

PMID- 10064404
TI  - Cutaneous T-lymphocyte infiltrate associated with B-cell chronic lymphocytic
      leukaemia.

PMID- 10064405
TI  - Cellular leiomyoma mimicking endometrial stromal neoplasm in association with
      GnRH agonist goserelin.

PMID- 10064406
TI  - Granulomatous mastitis: gray-scale and color Doppler sonographic findings.
AB  - PURPOSE: We examined the roles of gray-scale and color Doppler sonography in the
      diagnosis of granulomatous mastitis. METHODS: We retrospectively studied the
      clinical, mammographic, and sonographic findings in 10 women 24-57 years old
      (mean age, 35.9+/-13.9 years) who had a histopathologic diagnosis of
      granulomatous mastitis. All patients underwent gray-scale sonographic
      examination, and 8 patients were further examined with color Doppler imaging.
      Seven patients had previously undergone mammography. RESULTS: Mammographic
      findings were nonspecific in all 7 patients. Gray-scale sonographic findings were
      compatible with mastitis in 6 (60%) of 10 patients. Doppler examination showed
      increased arterial and venous vascularization within and around the lesion in 5
      of 8 patients, but the spectral analysis findings were not specific for
      granulomatous mastitis. CONCLUSIONS: Neither mammography nor Doppler sonography
      plays a significant role in the differential diagnosis of granulomatous mastitis
      versus fibroadenoma or carcinoma. Gray-scale sonography shows findings specific
      for granulomatous mastitis in some cases, but all cases require histopathologic
      confirmation for final diagnosis.

PMID- 10064407
TI  - Contrast-enhanced power Doppler sonography: improved detection of characteristic
      flow patterns in focal liver lesions.
AB  - PURPOSE: The aim of this study was to evaluate whether intravenous injection of
      an ultrasound contrast agent aids in the visualization of focal liver lesions on
      power Doppler images. METHODS: Fifty patients with focal liver lesions were
      studied by B-mode and power Doppler sonography before and after intravenous
      injection of the contrast agent Levovist (galactose-based microbubbles; 10 ml of
      a concentration of 300 mg/ml). Thirty-two patients had malignant liver lesions
      (19 metastases, 12 hepatocellular carcinomas, 1 cholangiocellular carcinoma),
      while 18 had benign lesions (12 hemangiomas, 2 focal nodular hyperplasias, 4
      others). RESULTS: After contrast medium injection, the number of lesions with no
      intralesional flow dropped from 18 to 9. Flow signal intensity was rated
      subjectively as marked on contrast-enhanced images in 17 patients; only 4
      patients had marked flow on precontrast images. On precontrast studies, central
      flow in 10 lesions and peripheral flow in 29 lesions could be observed. After
      enhancement, the numbers increased to 18 and 34 lesions, respectively.
      CONCLUSIONS: On power Doppler images, a greater number of intratumoral vessels
      are seen in focal liver lesions after contrast medium administration.

PMID- 10064408
TI  - Sonographic findings in cases of missed gallstones.
AB  - PURPOSE. We retrospectively evaluated sonographic findings in 946 cases of
      gallstones to determine whether the false-negative rate for gallstone detection
      by sonography has decreased as a result of technologic advances over the past 15
      years. METHODS: We reviewed preoperative sonographic reports, operative notes,
      and pathologic reports for 614 women and 332 men (ages 22-78 years) seen over a
      2.5-year period and compared sonographic findings with surgical pathologic
      findings after cholecystectomy. Sonograms for patients whose gallstones were
      missed on sonography were reviewed by 3 board-certified radiologists. RESULTS:
      Preoperative sonography of the gallbladder accurately predicted the presence of
      gallstones in 934 cases (98.7%). Gallstones were not identified by sonography in
      the remaining 12 cases. In those cases, sonography revealed polyps in 5, sludge
      in 5, sludge plus a polyp in 1, and neither stones nor polyps in 1. Thus, the
      false-negative rate was 1.3%. CONCLUSIONS: Despite improvements in sonographic
      technology, detection of small gallstones remains difficult in some cases.
      Adherent gallstones can mimic gallbladder polyps. Our false-negative rate for
      detection of gallstones was no different from that in earlier studies.

PMID- 10064409
TI  - Sonographically guided fine-needle aspiration biopsy of lytic lesions of the
      spine: technique and indications.
AB  - PURPOSE: We report the use of sonography to guide fine-needle aspiration biopsies
      (FNABs) of lytic lesions of the spine. METHODS: Twenty-nine patients with lytic
      vertebral lesions with or without associated extraosseous soft-tissue extension
      underwent sonographically guided FNAB. Twelve cervical, 7 thoracic, 7 lumbar, and
      3 sacral lesions were biopsied. Tissue samples were taken from either the bony
      lesion through a break in the cortex (n = 9) or the associated soft-tissue
      extension (n = 20). RESULTS: Adequate diagnostic material obtained in 27 cases
      (93%) revealed an inflammatory (n = 13) or malignant process (n = 14). Of the 2
      patients with inconclusive FNAB findings, 1 patient was lost to follow-up, and
      the other underwent surgery, which revealed tuberculosis. No complications of
      FNAB were encountered. CONCLUSIONS: We conclude that sonography is a safe and
      effective guidance modality for FNAB of lytic lesions of the spine, especially
      for lesions in the cervical region. In the thoracic, lumbar, and sacral regions,
      however, the role of sonographically guided FNAB is limited to lesions affecting
      the posterior elements.

PMID- 10064410
TI  - Transvaginal sonohysterographic evaluation of intrauterine adhesions.
AB  - PURPOSE: We assessed the role of preoperative sonohysterography in the diagnosis
      of intrauterine synechiae. METHODS: Nineteen patients with a suspected diagnosis
      of intrauterine adhesion underwent hysterosalpingography, transvaginal
      sonography, and sonohysterography performed in the consultation room. The
      patients were then treated by hysteroscopy under laparoscopic or ultrasound
      guidance. RESULTS: Transvaginal sonography showed an abnormal uterine cavity in
      only 10 cases. The sensitivities of sonohysterography and hysterosalpingography
      in the diagnosis of intrauterine adhesions were both 100%. Sonohysterography
      showed complete correlation with hysterosalpingography. CONCLUSIONS: We recommend
      routine sonohysterography after transvaginal sonography in cases of suspected
      intrauterine synechiae.

PMID- 10064411
TI  - Tissue harmonic imaging: utility in abdominal and pelvic sonography.

PMID- 10064412
TI  - Recurrent short rib-polydactyly syndrome with unusual associations.
AB  - Short rib-polydactyly syndrome (SRPS) is manifested by short-limb dwarfism, short
      ribs with thoracic hypoplasia, and polydactyly. This inheritable syndrome has
      distinct imaging findings on prenatal sonography, and ancillary findings on both
      pre- and postnatal assessments may enable individual cases to be classified into
      1 of 4 subtypes. In this report, we present a recurrent case of SRPS that was
      associated with a cystic hygroma and choroid plexus cysts. Although cystic
      hygromas are not uncommonly seen in skeletal dysplasias, the presence of
      concomitant cystic hygroma and choroid plexus cysts suggests a chromosomal
      abnormality such as trisomy 18.

PMID- 10064413
TI  - Infantile myofibromatosis of the triceps detected by prenatal sonography.
AB  - A routine prenatal sonographic examination at 36 weeks' menstrual age revealed a
      solid and slightly inhomogeneous soft-tissue tumor on a fetus's left upper arm.
      The mass in the left triceps brachii muscle measured 8 x 7 x 5 cm at birth.
      Because of progressive flexion contracture of the left elbow joint, at 2 months
      of age the infant underwent radical resection of the tumor, sparing some muscle
      fibers. Light microscopic and immunohistochemical studies revealed
      myofibromatosis. Neither tumor nor functional disorder of the arm was evident 3
      years after surgery.

PMID- 10064414
TI  - Intrahepatic artery pseudoaneurysm: a possible complication of blind
      thoracentesis.
AB  - We present a case of intrahepatic artery pseudoaneurysm that developed after
      blind thoracentesis in a 67-year-old man. This unusual complication demonstrates
      the value of sonographic guidance in reducing the risk of complications of
      thoracentesis.

PMID- 10064415
TI  - Preoperative sonographic diagnosis of sliding appendiceal inguinal hernia.
AB  - Rarely, the appendix forms the sliding component of an inguinal hernia. We report
      the case of a 2-month-old boy who was preoperatively diagnosed with sliding
      appendiceal inguinal hernia by sonographic examination. To our knowledge, this is
      the first report in the literature of the preoperative sonographic diagnosis of a
      sliding appendiceal inguinal hernia.

PMID- 10064416
TI  - Sonographic appearances and percutaneous management of primary tuberculous liver
      abscess.
AB  - Primary tuberculous liver abscesses are rare. We report on 3 patients who
      presented with a nonresolving abscess in the liver. Clinical presentation and
      sonographic findings in each case were nonspecific. A diagnosis of tuberculosis
      was established with microbiologic examination of pus in 2 cases and examination
      of an excised abscess wall in 1 case. Needle aspiration (1 patient) and short
      term (72 hours) catheter drainage (1 patient) were unsuccessful, and surgical
      excision was required in these patients. In the third patient, continuous
      catheter drainage over 18 days resulted in cure, indicating that long-term
      catheter drainage with antituberculous chemotherapy may be a viable alternative
      to surgery in the management of primary tuberculous liver abscess.

PMID- 10064417
TI  - New sonographic appearance of hepatic mesenchymal hamartoma in childhood.
AB  - We present clinical, radiographic, and sonographic findings in 3 children with
      hepatic mesenchymal hamartoma, a rare benign tumor of childhood. The presence of
      round hyperechoic parietal nodules within the cystic spaces of the hamartomas is
      a new sonographic finding.

PMID- 10064418
TI  - Neonatal hearing screening using otoacoustic emissions elicited by maximum length
      sequences.
AB  - The aim of this study was to provide statistical information on otoacoustic
      emission (OAE) measurements in new-born infants, which could be useful in the
      interpretation of results and could add some clinical parameters that might be
      used for future objective and automatic response evaluations. Transient evoked
      OAEs (TEOAEs) using maximum length sequences (MLS) were recorded in 129 full-term
      new-born infants between 48 and 72 hours of age. The use of MLS enabled stimulus
      rates of up to 2000/sec to be utilized. The analysis comprised five main issues:
      (1) signal to noise ratio (S/N); (2) derived non-linear responses; (3) a
      combination of derived non-linear emissions called compound non-linear emissions;
      (4) time/frequency analysis and (5) signal power analysis. The result of the
      analysis were as follows. (1) The largest S/N ratio was obtained when more than
      60% of the recordings were rejected. (2) The derived non-linear emissions
      comprised level non-linear and rate non-linear responses, the latter obtained by
      subtraction of recordings at fixed stimulus level, but at different stimulus
      rates. The rapid suppression of emission amplitude as the stimulus rate increases
      is the basis for this non-linear response which also features stimulus
      cancellation. (3) The compound non-linear emissions, consisting of a sum of
      derived non-linear responses may prove efficient by proper selection of stimulus
      parameters, but did not in the present form show the expected improvements of
      amplitude and stimulus cancellation. (4) The time/frequency analysis, however,
      based on calculations of the instantaneous frequency as a function time after
      stimulus onset, showed a consistent tendency of falling frequency versus time
      after stimulus onset as a basic characteristic feature of OAE. (5) The analysis
      of the emission power as a function of time after stimulus onset showed that
      linear recordings in new-born infants are reliable, with stimulus ringing fully
      decayed 3 ms after the stimulus onset. The findings may prove useful in future
      attempts to develop screening equipment with automatic response evaluation for
      new-born infants. From a clinical point of view the MLS technique was successful
      when measuring emissions in neonates, owing to the fast recording time and the
      utilization of an efficient noise rejection paradigm.

PMID- 10064419
TI  - Amplitude compression in cochlear implants artificially restricts the perception
      of temporal asymmetry.
AB  - This paper presents a study in which five cochlear implantees were asked to
      discriminate the timbre of stimuli with temporally asymmetric envelopes. Stimuli
      were damped and ramped sinusoids presented acoustically. They were transformed by
      the speech processor of the implant and were presented through one electrode. All
      cochlear implantees could discriminate the damped and ramped sinusoids when the
      half-life was 4 ms, the carrier frequency was 400 Hz, and the period of the
      envelope was 50 ms. In a second experiment, timbre discrimination performance was
      measured as a function of half-life for two cochlear implantees. Both showed that
      timbre discrimination was possible over the range 1-24 ms. In normal-hearing
      listeners, the range is 1-64 ms and in cochlear implantees, stimulated directly
      without the speech processor, the range is 1-300 ms. At long half-lives, the
      decrease in discrimination performance observed with the speech processor appears
      to be due to the amplitude compression applied by the device. The present results
      suggest that it may be important to ensure that cochlear implants do not restrict
      temporal asymmetry unduly when applying compression to control level.

PMID- 10064420
TI  - Psychometric evaluation of the Gothenburg Profile for measurement of experienced
      hearing disability and handicap: applications with new hearing aid candidates and
      experienced hearing aid users.
AB  - The Gothenburg Profile (GP) for measurement of experienced hearing disability and
      handicap was developed with content partly taken from the shortened Hearing
      Measurement Scale (HMS25). The GP consists of 20 items divided into two
      subscales. The first subscale measures Experienced Disability as to hearing
      speech (items 1-5) and sound localization (items 6-10). The second subscale
      targets the Experienced Handicap in social settings (items 11-15) and the
      personal reactions to the experienced handicap (items 16-20). In this study, data
      are presented for new hearing aid candidates (NewHA) (n=441) and for experienced
      hearing aid users (ExpHA) (n=476). Principal components factor analyses were
      conducted and a three-factor solution was obtained, supporting the two factors of
      the Experienced Disability subscale, but just confirming one factor in the
      Experienced Handicap subscale. The internal consistency reliability (coefficient
      alpha) was good (0.85 to 0.95) for the subscales as was the test-retest
      reliability. The ExpHA group expressed significantly greater disability (first
      subscale) as well as experienced handicap (second subscale). However, when
      controlling for hearing level the differences disappeared. The clinical use of
      the GP for assessment of rehabilitation needs is recommended.

PMID- 10064421
TI  - The influence of body temperature on transient evoked otoacoustic emissions.
AB  - Thirty patients undergoing open heart surgery under induced hypothermia had
      transient evoked otoacoustic emissions (TEOAE) recorded during cooling to 26.07
      degrees C (standard deviation (SD) 4.25 degrees C) vesically measured temperature
      and 24.86 degrees C (SD 4.7 degrees C) nasopharyngeally measured temperature
      respectively. Subsequently te patients were rewarmed until normal body
      temperature was reached again. There was a clear influence of body temperature on
      the amplitudes and reproducibilities of the TEOAE. The relationship of
      temperature and amplitude or reproducibility during the cooling phase was
      significantly different from that during rewarming. No TEOAE were measurable
      during cooling at a mean temperature lower than 33.41 degrees C (SD 2.04 degrees
      C) vesical temperature and 30.16 degrees C (SD 3.0 degrees C) nasopharyngeal
      temperature respectively. During rewarming the echoes became recognizable again
      at a mean temperature of 28.75 degrees C (SD 3.38 degrees C) vesical temperature
      and 27.49 degrees C (SD 2.99 degrees C) nasopharyngeal temperature. These results
      suggest a hysteresis in the relationship between the amplitude of TEOAE and
      temperature, similar to the well-established relationship between evoked
      potentials and temperature.

PMID- 10064422
TI  - Anomalous screening outcomes from click-evoked otoacoustic emissions and auditory
      brainstem response tests.
AB  - Transiently evoked otoacoustic emissions (TEOAE) and auditory brainstem response
      (ABR) tests were used in parallel to screen 862 neonates with risk factors for
      hearing loss. Seven neonates (0.81%) passed on TEOAE screen yet failed on ABR in
      one ear (six neonates) or both ears (one neonate). This combination of results
      has been termed 'anomalous'. Examination of audiometric results obtained on
      follow-up shows that in one ear of one neonate the result was consistent with the
      later confirmed audiogram shape. The explanation for the anomalous results in the
      remaining ears is unclear although neural maturation and the effects of
      hyperbilirubinaemia are possibilities. There were no instances of progressive or
      retrocochlear hearing loss identified. None of the seven neonates had better ear
      hearing loss of > or = 40 dB on long term follow-up.

PMID- 10064423
TI  - Video-oculography as part of the ENG battery.
AB  - Recording and quantifying eye movement is the basis of audiologic balance
      testing. The ability to record and quantify eye movement is a key part of the
      electronystagmography (ENG) test battery. With computerization, eye movements can
      be more accurately detected and analysed--testing the limits of the standard
      recording technique. In response to this, manufacturers are introducing
      alternative recording protocols. Specifically, infra-red video technology allows
      an accurate and sophisticated recording and analysis of eye motion in response to
      balance-related stimuli. The purpose of this technical note is to discuss the
      limitations of the EOG recording method and discuss the advantages that video
      oculography offers.

PMID- 10064533
TI  - Lattice Effects in the Colossal-Magnetoresistance Manganites

PMID- 10064540
TI  - Variational Principle for Eigenvalue Problems of Hamiltonian Systems

PMID- 10064541
TI  - Dynamical Entropies Applied to Stochastic Resonance

PMID- 10064544
TI  - Developmental pathways: Sonic hedgehog-Patched-GLI.
AB  - Developmental pathways are networks of genes that act coordinately to establish
      the body plan. Disruptions of genes in one pathway can have effects in related
      pathways and may result in serious dysmorphogenesis or cancer. Environmental
      exposures can be associated with poor pregnancy outcomes, including dysmorphic
      offspring or children with a variety of diseases. An important goal of
      environmental science should be reduction of these poor outcomes. This will
      require an understanding of the genes affected by specific exposures and the
      consequence of alterations in these genes or their products, which in turn will
      require an understanding of the pathways critical in development. The ligand
      Sonic hedgehog, the receptors Patched and Smoothened, and the GLI family of
      transcription factors represent one such pathway. This pathway illustrates
      several operating principles important in the consideration of developmental
      consequences of environmental exposures to toxins.

PMID- 10064545
TI  - Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast
      carcinoma cell line.
AB  - Estrogens, whether natural or synthetic, clearly influence reproductive
      development, senescence, and carcinogenesis. Pyrethroid insecticides are now the
      most widely used agents for indoor pest control, providing potential for human
      exposure. Using the MCF-7 human breast carcinoma cell line, we studied the
      estrogenic potential of several synthetic pyrethroid compounds in vitro using pS2
      mRNA levels as the end point. We tested sumithrin, fenvalerate, d-trans
      allethrin, and permethrin. Nanomolar concentrations of either sumithrin or
      fenvalerate were sufficient to increase pS2 expression slightly above basal
      levels. At micromolar concentrations, these two pyrethroid compounds induced pS2
      expression to levels comparable to those elicited by 10 nM 17ss-estradiol
      (fivefold). The estrogenic activity of sumithrin was abolished with co-treatment
      with an antiestrogen (ICI 164,384), whereas estrogenic activity of fenvalerate
      was not significantly diminished with antiestrogen co-treatment. In addition,
      both sumithrin and fenvalerate were able to induce cell proliferation of MCF-7
      cells in a dose-response fashion. Neither permethrin nor d-trans allethrin
      affected pS2 expression. Permethrin had a noticeable effect on cell proliferation
      at 100 microM, whereas d-trans allethrin slightly induced MCF-7 cell
      proliferation at 10 microM, but was toxic at higher concentrations. Overall, our
      studies imply that each pyrethroid compound is unique in its ability to influence
      several cellular pathways. These findings suggest that pyrethroids should be
      considered to be hormone disruptors, and their potential to affect endocrine
      function in humans and wildlife should be investigated.

PMID- 10064546
TI  - Relationships between environmental organochlorine contaminant residues, plasma
      corticosterone concentrations, and intermediary metabolic enzyme activities in
      Great Lakes herring gull embryos.
AB  - Experiments were conducted to survey and detect differences in plasma
      corticosterone concentrations and intermediary metabolic enzyme activities in
      herring gull (Larus argentatus) embryos environmentally exposed to organochlorine
      contaminants in ovo. Unincubated fertile herring gull eggs were collected from an
      Atlantic coast control site and various Great Lakes sites in 1997 and
      artificially incubated in the laboratory. Liver and/or kidney tissues from
      approximately half of the late-stage embryos were analyzed for the activities of
      various intermediary metabolic enzymes known to be regulated, at least in part,
      by corticosteroids. Basal plasma corticosterone concentrations were determined
      for the remaining embryos. Yolk sacs were collected from each embryo and a subset
      was analyzed for organochlorine contaminants. Regression analysis of individual
      yolk sac organochlorine residue concentrations, or 2,3,7,8-tetrachlorodibenzo-p
      dioxin equivalents (TEQs), with individual basal plasma corticosterone
      concentrations indicated statistically significant inverse relationships for
      polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDDs/PCDFs),
      total polychlorinated biphenyls (PCBs), non-ortho PCBs, and TEQs. Similarly,
      inverse relationships were observed for the activities of two intermediary
      metabolic enzymes (phosphoenolpyruvate carboxykinase and malic enzyme) when
      regressed against PCDDs/PCDFs. Overall, these data suggest that current levels of
      organochlorine contamination may be affecting the hypothalamo-pituitary-adrenal
      axis and associated intermediary metabolic pathways in environmentally exposed
      herring gull embryos in the Great Lakes.

PMID- 10064547
TI  - Study of the effect of lactational bone loss on blood lead concentrations in
      humans.
AB  - Lactation and other clinical states of high bone turnover have been suggested to
      release lead (Pb) stored in bone into blood and tissues. Previous observations on
      the influences of lactation have been anecdotal, or at high blood Pb
      concentrations with varying past exposures, or complicated by postpartum fluid
      changes. A prospective observational study was performed to investigate possible
      changes in blood lead concentrations at multiple intervals during lactation for 6
      months postpartum and to relate changes in blood lead concentrations to changes
      in bone density and other variables. Volunteer pregnant subjects (n = 58) were
      enrolled from a midwifery service at an academic public health hospital. Subjects
      were mostly Hispanic, recently immigrated, of low economic status, not receiving
      supplemental calcium, and had low blood Pb concentrations (2.35 +/- 2.05
      microg/dl at enrollment). Bone density losses over 6 months for the group
      averaged -2.46 +/- 6.33% at the vertebral spine and -0.67 +/- 5.21% at the
      femoral neck. In predicting final bone density, apart from initial bone density
      only the total number of breast-feedings was a significant independent variable
      of the variables tested, accounting for an additional 12% of the variability. No
      changes in blood Pb concentrations were seen over the interval beyond 2 weeks
      postpartum (minimum detectable change was 0.4 microg/dl). There was no relation
      between the changes in bone density and changes in blood Pb or the integrated
      blood Pb over the 2-week to 6-month period. Normal (nonlactating) bone resorption
      rates contribute a large fraction of the Pb in blood during low-exposure
      circumstances. However, during lactation the increase in bone resorptive
      processes is probably relatively small with a larger decrease in deposition
      accounting for net bone loss, as suggested by other investigations. Thus,
      concomitant release of Pb from bones of lactating subjects with low blood lead
      concentrations on this background of high normal resorption was not large enough
      for detection.

PMID- 10064548
TI  - Effect of magnetic field exposure on anchorage-independent growth of a promoter
      sensitive mouse epidermal cell line (JB6).
AB  - The anchorage-independent growth of mouse epidermal cells (JB6) exposed to 60-Hz
      magnetic fields (MF) was investigated. Promotion-responsive JB6 cells were
      suspended in agar (10(4)cells/plate) and exposed continuously to 0.10 or 0.96 mT,
      60-Hz magnetic fields for 10-14 days, with or without concurrent treatment with
      the tumor promoter tetradecanoylphorbol acetate (TPA). Exposures to MF were
      conducted in a manner such that the experimenter was blind to the treatment group
      of the cells. At the end of the exposure period, the anchorage-independent growth
      of JB6 cells on soft agar was examined by counting the number of colonies larger
      than 60 microm (minimum of 60 cells). The use of a combined treatment of the
      cells with both MF and TPA was to provide an internal positive control to
      estimate the success of the assay and to allow evaluation of co-promotion.
      Statistical analysis was performed by a randomized block design analysis of
      variance to examine both the effect of TPA treatment (alone and in combination
      with MF exposure) and the effect of intra-assay variability. Transformation
      frequency of JB6 cells displayed a dose-dependent response to increasing
      concentrations of TPA. Coexposure of cells to both TPA and 0.10 or 0.96 mT, 60-Hz
      MF did not result in any differences in transformation frequency for any TPA
      concentrations tested (0-1 ng/ml). These data indicate that exposure to a 0.10 or
      0.96 mT, 60-Hz MF does not act as a promoter or co-promoter in promotion
      sensitive JB6 cell anchorage-independent growth.

PMID- 10064549
TI  - A comparison of the reproductive physiology of largemouth bass, Micropterus
      salmoides, collected from the Escambia and Blackwater Rivers in Florida.
AB  - Largemouth bass (LMB), Micropterus salmoides, were taken from the Escambia River
      (contaminated site) and the Blackwater River (reference site) near Pensacola,
      Florida. The Escambia River collection occurred downstream of the effluent from
      two identified point sources of pollution. These point sources included a coal
      fired electric power plant and a chemical company. Conversely, the Blackwater
      River's headwaters and most of its length flow within a state park. Although
      there is some development on the lower part of the Blackwater River, fish were
      collected in the more pristine upper regions. Fish were captured by
      electroshocking and were maintained in aerated coolers. Physical measurements
      were obtained, blood was taken, and liver and gonads were removed. LMB plasma was
      assayed for the concentration of 17ss-estradiol (E2) and testosterone using
      validated radioimmunoassays. The presence of vitellogenin was determined by gel
      electrophoresis (SDS-PAGE) and Western blotting using a monoclonal antibody
      validated for largemouth bass vitellogenin. No differences in plasma
      concentrations of E2 or testosterone were observed in females from the two sites.
      Similarly, males exhibited no difference in plasma E2. However, plasma
      testosterone was lower in the males from the contaminated site, as compared to
      the reference site. Vitellogenic males occurred only at the contaminated site.
      Additionally, liver mass was proportionately higher in males from the
      contaminated site, as compared to males from the reference site. These data
      suggest that reproductive steroid levels may have been altered by increased
      hepatic enzyme activity, and the presence of vitellogenic males indicates that an
      exogenous source of estrogen was present in the Escambia River.

PMID- 10064550
TI  - Cancer mortality in agricultural regions of Minnesota.
AB  - Because of its unique geology, Minnesota can be divided into four agricultural
      regions: south-central region one (corn, soybeans); west-central region two
      (wheat, corn, soybeans); northwest region three (wheat, sugar beets, potatoes);
      and northeast region four (forested and urban in character). Cancer mortality
      (1980-1989) in agricultural regions one, two, and three was compared to region
      four. Using data compiled by the National Center for Health Statistics, cancer
      mortality was summarized by 5-year age groups, sex, race, and county. Age
      standardized mortality rate ratios were calculated for white males and females
      for all ages combined, and for children aged 0-14. Increased mortality rate
      ratios and 95% confidence intervals (CIs) were observed for the following cancer
      sites: region one--lip (men), standardized rate ratio (SRR) = 2.70 (CI, 1.08
      6.71); nasopharynx (women), SRR = 3.35 (CI, 1.20-9.31); region two--non-Hodgkin's
      lymphoma (women), SRR = 1.35 (CI, 1.09-1.66); and region three--prostate (men),
      SRR = 1.12 (CI, 1.00-1.26); thyroid (men), SRR = 2.95 (CI, 1.35-6.44); bone
      (men), SRR = 2.09 (CI, 1. 00-4.34); eye (women), SRR = 5.77 (CI, 1.90-17.50).
      Deficits of smoking-related cancers were noted. Excess cancers reported are
      consistent with earlier reports of agriculturally related cancers in the
      midwestern United States. However, reports on thyroid and bone cancer in
      association with agricultural pesticides are few in number. The highest use of
      fungicides occurs in region three. Ethylenebisdithiocarbamates, whose metabolite
      is a known cause of thyroid cancer in rats, are frequently applied. This report
      provides a rationale for evaluation of the carcinogenic potential of this suspect
      agent in humans.

PMID- 10064551
TI  - Exposure to indoor background radiation and urinary concentrations of 8
      hydroxydeoxyguanosine, a marker of oxidative DNA damage.
AB  - We investigated whether exposure to indoor [gamma]-radiation and radon might be
      associated with enough free radical formation to increase urinary concentrations
      of 8-hydroxydeoxyguanosine (8-OHdG), a sensitive marker of DNA damage, due to a
      hydroxyl radical attack at the C8 of guanine. Indoor radon and [gamma]-radiation
      levels were measured in 32 dwellings for 6 months by solid-state nuclear track
      detectors and thermoluminescent dosimeters, respectively. Urine samples for 8
      OHdG determinations were obtained from 63 healthy adult subjects living in the
      measured dwellings. An overall tendency toward increasing levels of 8-OHdG with
      increasing levels of radon and [gamma]-radiation was seen in the females,
      presumably due to their estimated longer occupancy in the dwellings measured.
      Different models were considered for females, with the steepest slopes obtained
      for [gamma]-radiation with a coefficient of 0.500 (log nmol/l of 8-OHdG for each
      unit increase of [gamma]-radiation on a log scale) (p<0.01), and increasing to
      0.632 (p = 0.035), but with larger variance, when radon was included in the
      model. In conclusion, there seems to be an effect of indoor radioactivity on the
      urinary excretion of 8-OHdG for females, who are estimated to have a higher
      occupancy in the dwellings measured than for males, for whom occupational and
      other agents may also influence 8-OHdG excretion. ree radicals; [gamma]
      radiation; radon.

PMID- 10064552
TI  - A simulation study of confounding in generalized linear models for air pollution
      epidemiology.
AB  - Confounding between the model covariates and causal variables (which may or may
      not be included as model covariates) is a well-known problem in regression models
      used in air pollution epidemiology. This problem is usually acknowledged but
      hardly ever investigated, especially in the context of generalized linear models.
      Using synthetic data sets, the present study shows how model overfit, underfit,
      and misfit in the presence of correlated causal variables in a Poisson regression
      model affect the estimated coefficients of the covariates and their confidence
      levels. The study also shows how this effect changes with the ranges of the
      covariates and the sample size. There is qualitative agreement between these
      study results and the corresponding expressions in the large-sample limit for the
      ordinary linear models. Confounding of covariates in an overfitted model (with
      covariates encompassing more than just the causal variables) does not bias the
      estimated coefficients but reduces their significance. The effect of model
      underfit (with some causal variables excluded as covariates) or misfit (with
      covariates encompassing only noncausal variables), on the other hand, leads to
      not only erroneous estimated coefficients, but a misguided confidence,
      represented by large t-values, that the estimated coefficients are significant.
      The results of this study indicate that models which use only one or two air
      quality variables, such as particulate matter [less than and equal to] 10 microm
      and sulfur dioxide, are probably unreliable, and that models containing several
      correlated and toxic or potentially toxic air quality variables should also be
      investigated in order to minimize the situation of model underfit or misfit.

PMID- 10064553
TI  - Indoor, outdoor, and regional summer and winter concentrations of PM10, PM2.5,
      SO4(2)-, H+, NH4+, NO3-, NH3, and nitrous acid in homes with and without kerosene
      space heaters.
AB  - Twenty-four-hour samples of PM10 (mass of particles with aerodynamic diameter <
      or = 10 microm), PM2.5, (mass of particles with aerodynamic diameter < or = 2.5
      microm), particle strong acidity (H+), sulfate (SO42-), nitrate (NO3-), ammonia
      (NH3), nitrous acid (HONO), and sulfur dioxide were collected inside and outside
      of 281 homes during winter and summer periods. Measurements were also conducted
      during summer periods at a regional site. A total of 58 homes of nonsmokers were
      sampled during the summer periods and 223 homes were sampled during the winter
      periods. Seventy-four of the homes sampled during the winter reported the use of
      a kerosene heater. All homes sampled in the summer were located in southwest
      Virginia. All but 20 homes sampled in the winter were also located in southwest
      Virginia; the remainder of the homes were located in Connecticut. For homes
      without tobacco combustion, the regional air monitoring site (Vinton, VA)
      appeared to provide a reasonable estimate of concentrations of PM2.5 and SO42-
      during summer months outside and inside homes within the region, even when a
      substantial number of the homes used air conditioning. Average indoor/outdoor
      ratios for PM2.5 and SO42- during the summer period were 1.03 +/- 0.71 and 0.74
      +/- 0.53, respectively. The indoor/outdoor mean ratio for sulfate suggests that
      on average approximately 75% of the fine aerosol indoors during the summer is
      associated with outdoor sources. Kerosene heater use during the winter months, in
      the absence of tobacco combustion, results in substantial increases in indoor
      concentrations of PM2.5, SO42-, and possibly H+, as compared to homes without
      kerosene heaters. During their use, we estimated that kerosene heaters added, on
      average, approximately 40 microg/m3 of PM2.5 and 15 microg/m3 of SO42- to
      background residential levels of 18 and 2 microg/m3, respectively. Results from
      using sulfuric acid-doped Teflon (E.I. Du Pont de Nemours & Co., Wilmington, DE)
      filters in homes with kerosene heaters suggest that acid particle concentrations
      may be substantially higher than those measured because of acid neutralization by
      ammonia. During the summer and winter periods indoor concentrations of ammonia
      are an order of magnitude higher indoors than outdoors and appear to result in
      lower indoor acid particle concentrations. Nitrous acid levels are higher indoors
      than outdoors during both winter and summer and are substantially higher in homes
      with unvented combustion sources.

PMID- 10064554
TI  - Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA
      adduct levels with other exposure markers and markers for oxidative stress.
AB  - Human exposure to genotoxic compounds present in ambient air has been studied
      using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A
      large interindividual variation in biomarker levels was observed. Significantly
      higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides)
      and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg
      protein) were observed in bus drivers working in the central part of Copenhagen,
      Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8
      pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and
      polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin)
      were observed in the suburban group. The biomarker levels in postal workers were
      similar to the levels in suburban bus drivers. In the combined group of bus
      drivers and postal workers, negative correlations were observed between bulky
      carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct
      and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly
      significant correlations were found between PAH-albumin adducts and AAS in plasma
      (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also
      observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma
      (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione
      S-transferase (GST) M1 deletion on the correlation between the biomarkers was
      studied in the combined group. A significant negative correlation was only
      observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02)
      and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1
      null group, but not in the workers who were homozygotes or heterozygotes for
      GSTM1. Our results indicate that some of the selected biomarkers can be used to
      distinguish between high and low exposure to environmental genotoxins.

PMID- 10064555
TI  - Cockroach allergy and asthma in a 30-year-old man.
AB  - A growing body of evidence has implicated allergens derived from cockroaches as
      an important environmental factor that may aggravate asthma in sensitized
      persons. We present the case of a 30-year-old man with asthma and a cockroach
      allergy. Allergy skin testing confirmed hypersensitivity to cockroach extract,
      and a home visit revealed visual evidence of infestation and the presence of Bla
      g 1 German cockroach allergen in vacuumed dust. As is typical of patients with a
      cockroach allergy and asthma, multiple factors in addition to cockroach allergen
      appeared to aggravate the patient's asthma. A multimodality therapeutic regimen,
      which included medications as well as cleaning of the home, integrated pest
      management, and professional application of chemical controls, resulted in
      substantial clinical improvement. The pathophysiology, epidemiology, and clinical
      features of cockroach-allergic asthma are reviewed, and an approach to diagnosis
      and management is suggested.

PMID- 10064556
TI  - Bone mineral density and gene-environment interactions in the search for
      osteoporosis genes.

PMID- 10064557
TI  - An all-consuming issue.

PMID- 10064558
TI  - Organic: What's in a name?
AB  - The organic foods industry is booming: by one estimate, the market for organic
      foods is worth $4 billion annually and is expected to grow at a rate of more than
      24% per year. Faced with the threat of pesticide exposures and other food safety
      problems, many consumers are turning to organic foods in hopes of finding a
      healthy alternative, but there is currently no consistency in organic food
      labeling and no guarantee that foods labeled as organic are actually grown and
      processed in a purely organic fashion. There is also controversy about whether
      the label "organic" covers such new technologies as irradiation and genetic
      engineering. As part of the 1990 Farm Bill, the U.S. Department of Agriculture
      (USDA) is working to develop a proposed rule on organic foods. The rule would
      regulate the allowable methods, practices, and substances used in producing and
      handling crops and their processed products. The first draft of the proposed
      rule, released in December 1997, met with unprecedented opposition, which
      centered around the fact that the proposal appeared to virtually ignore the
      recommendations of a standards board formed to assist in the rule's development.
      Other criticism opposed three practices put forward for comment by the USDA:
      irradiation, genetic engineering, and the use of sewage sludge in farming. Due to
      the vehemence of the opposition to its original proposal, the USDA has decided to
      rewrite the proposed rule. In preparation for that proposal, the USDA
      Agricultural Marketing Service released three issue papers in October 1998 for
      public comment. The 10,000-plus comments received in response to those papers
      will be incorporated into the second draft proposal, due out later this year.

PMID- 10064559
TI  - Fresh from the farm.

PMID- 10064560
TI  - Metabolism of retinaldehyde isomers in pregnant rats: 13-cis- and all-trans
      retinaldehyde, but not 9-cis-retinaldehyde, yield very similar patterns of
      retinoid metabolites.
AB  - Retinaldehyde (RAL), a key intermediate in retinoid metabolism, acts as a
      retinoic acid (RA) precursor, but is also reduced to retinol (ROH), which can
      subsequently be esterified to retinyl esters, the storage form of vitamin A.
      Limited information is available on the metabolism of geometric isomers of RAL as
      well as on the transplacental distribution of their metabolites, including RA
      isomers. Such information would be very helpful for the assessment of the
      teratogenic potency of RAL isomers, as teratogenesis represents a major side
      effect of retinoid use in pharmacotherapy. In the present study we examined
      concentrations of retinoids in plasma, maternal tissues, and embryos of pregnant
      rats 2 h after a single oral dose (100 mg/kg body weight) of all-trans-, 13-cis-,
      or 9-cis-RAL on gestational day 13. The main findings of this study were the very
      similar patterns of retinoid metabolites (consisting of retinoids with mainly the
      all-trans-configuration) after administration of all-trans- and 13-cis-RAL, and
      the high concentrations of 9-cis-RA, 9,13-dicis-RA, and 9-cis-retinoyl-beta-D
      glucuronide after dosing with 9-cis-RAL. In addition, all-trans-RA as a RAL
      metabolite reached the embryos to a much greater extent than any of its cis
      isomers. The results are discussed in view of in vitro data on enzymes involved
      in the biotransformation of RAL isomers.

PMID- 10064561
TI  - Involvement of cytochromes P-450 2E1 and 3A4 in the 5-hydroxylation of salicylate
      in humans.
AB  - Hydroxylation of salicylate into 2,3 and 2,5-dihydroxybenzoic acids (2,3-DHBA and
      2,5-DHBA) by human liver microsomal preparations was investigated. Kinetic
      studies demonstrated that salicylate was 5-hydroxylated with two apparent Km: one
      high-affinity Km of 606 microM and one low-affinity Km greater than 2 mM. Liver
      microsomes prepared from 15 human samples catalyzed the formation of 2,5-DHBA at
      metabolic rate of 21.7 +/- 8.5 pmol/mg/min. The formation of 2, 3-DHBA was not P
      450 dependent. Formation of 2,5-DHBA was inhibited by 36 +/- 14% following
      preincubation of microsomes with diethyldithiocarbamate, a mechanism-based
      selective inhibitor of P-450 2E1. Furthermore, the efficiency of inhibition was
      significantly correlated with four catalytic activities specific to P-450 2E1,
      whereas the residual activity was correlated with three P-450 3A4 catalytic
      activities. Troleandomycin, a mechanism-based inhibitor selective to P-450 3A4,
      inhibited by 30 +/- 12% the 5-hydroxylation of salicylate, and this inhibition
      was significantly correlated with nifedipine oxidation, specific to P-450 3A4.
      The capability of seven recombinant human P-450s to hydroxylate salicylate
      demonstrated that P-450 2E1 and 3A4 contributed to 2, 5-DHBA formation in
      approximately equal proportions. The Km values of recombinant P-450 2E1 and 3A4,
      280 and 513 microM, respectively, are in the same range as the high-affinity Km
      measured with human liver microsomes. The plasmatic metabolic ratio 2,5
      DHBA/salicylate, measured 2 h after ingestion of 1 g acetylsalicylate, was
      increased 3-fold in 12 alcoholic patients at the beginning of their withdrawal
      period versus 15 control subjects. These results confirm that P-450 2E1,
      inducible by ethanol, is involved in the 5-hydroxylation of salicylate in humans.
      Furthermore, this ratio was still increased by 2-fold 1 week after ethanol
      withdrawal. This finding suggests that P-450 3A4, known to be also inducible by
      alcoholic beverages, plays an important role in this increase, because P-450 2E1
      returned to normal levels in less than 3 days after ethanol withdrawal. Finally,
      in vivo and in vitro data demonstrated that P-450 2E1 and P-450 3A4, both
      inducible by alcohols, catalyzed the 5-hydroxylation of salicylate.

PMID- 10064562
TI  - Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat
      hepatocytes.
AB  - In the present study, we evaluated the inducibility of cytochrome P-450 (CYP)
      CYP1A, CYP2B, CYP3A, and CYP4A by beta-naphthoflavone, phenobarbital,
      dexamethasone, and clofibric acid, respectively, in primary hepatocyte cultures
      prepared from both fresh and cryopreserved rat hepatocytes. Rat hepatocytes were
      successfully thawed and cultured after cryopreservation in liquid nitrogen for up
      to 1 month. Percentage of total recovery, viable cell recovery, and final
      viability of the cells were 68%, 72%, and 85%, respectively. Regardless of
      whether they were cryopreserved or not, cultured hepatocytes exhibited near
      normal morphology. Treatment of cryopreserved hepatocytes with beta
      naphthoflavone caused an 8-fold increase in 7-ethoxyresorufin O-dealkylase
      (CYP1A1/2) activity, with an EC50 of 1.5 microM; treatment with phenobarbital
      caused a 26-fold increase in 7-pentoxyresorufin O-dealkylase (CYP2B1/2) activity,
      with an EC50 of 10 microM; treatment with dexamethasone caused a 10-fold increase
      in testosterone 6beta-hydroxylase (CYP3A1/2) activity, with an EC50 of 1.3
      microM, whereas treatment with clofibric acid caused a 3-fold increase in lauric
      acid 12-hydroxylase (CYP4A1-3) activity, with an EC50 of 170 microM. The
      induction of CYP1A, CYP2B, CYP3A, and CYP4A enzymes by these inducers was
      confirmed by Western immunoblotting. The patterns of P-450 induction in
      cryopreserved rat hepatocytes, in terms of concentration response,
      reproducibility, magnitude, and specificity of response, were similar to those
      observed in freshly isolated hepatocytes. Additionally, the magnitude and
      specificity of induction was similar to that observed in vivo in rats. In
      conclusion, under the conditions examined, cryopreserved rat hepatocytes appear
      to be a suitable in vitro system for evaluating xenobiotics as inducers of P-450
      enzymes.

PMID- 10064563
TI  - Lack of zonal uptake of estrone sulfate in enriched periportal and perivenous
      isolated rat hepatocytes.
AB  - The zonal uptake of estrone sulfate (E1S; 1 to 400 microM) was investigated in
      periportal and perivenous rat hepatocytes and cells isolated from whole liver
      (regular hepatocytes). Transport of E1S by periportal, perivenous, and regular
      hepatocytes was described by saturable (Kms of 24 to 26 microM and Vmaxs of 1.8
      nmol/min/mg protein) and nonsaturable components (2.5 to 3.2 microl/min/mg
      protein) that were not different among the zonal regions (p >.05, ANOVA). These
      kinetic constants represented pooled values for the entire complement of
      transporters for E1S, including two known transporters of E1S: Ntcp, Na+
      taurocholate cotransporting polypeptide, and oatp1, the organic anion
      transporting polypeptide cloned from rat liver. Uptake of E1S was significantly
      reduced by estradiol 17beta-glucuronide (50 microM) and bumetanide (200 microM),
      and was inhibited strongly and competitively by pregnenolone sulfate with an
      inhibition constant of 6.7 microM. Further segregation of the kinetic constants
      as the sodium-dependent and -independent systems was achieved through
      simultaneous fitting of data obtained in the presence and absence of sodium from
      parallel hepatocytic uptake studies. For the periportal, perivenous, and regular
      hepatocytes, two saturable systems: a sodium-dependent transport system,
      characterized by similar Vmaxs (1.1 to 1.4 nmol/min/mg protein) and Kms (49 to 55
      microM), a sodium-independent transport system of comparable Vmaxs (0.70 to 0.84
      nmol/min/mg protein) and Kms (16 to 22 microM), and a linear clearance of 1.7 to
      2.7 microl/min/mg protein (ANOVA, p >.05) were obtained. The data suggest that
      hepatic uptake of E1S involved sodium-dependent and -independent transporter
      systems. No heterogeneity in transport was observed.

PMID- 10064564
TI  - Metabolism of the new liposomal anticancer drug N4-octadecyl-1-beta-D
      arabinofuranosylcytosine in mice.
AB  - Metabolism and excretion of the new antitumor drug N4-octadecyl-1-beta-D
      arabinofuranosylcytosine (NOAC) was investigated in mice. Mice were injected i.v.
      with tritium-labeled liposomal NOAC (4 micromol/mouse). Analysis of HPLC-purified
      extracts of liver homogenates by liquid chromatography coupled with mass
      spectrometry revealed only the presence of unmetabolized drug. To study the
      excretion of the administered drug, mice were injected with tritium-labeled
      liposomal NOAC or as comparison with 1-beta-D-arabinofuranosylcytosine (ara-C; 4
      micromol/mouse) and housed up to 48 h in metabolic cages. Urine and feces were
      collected at different time points and the kinetics of excreted radioactivity
      were determined. After 48 h, 39% of the injected [5-3H]NOAC radioactivity was
      excreted in urine and 16% in feces, whereas ara-C radioactivity was only found in
      urine with 48% of the injected dose. Feces extracts and urine were purified by
      HPLC and radioactive fractions were further analyzed by liquid chromatography
      coupled with mass spectrometry. The radioactivity of feces extracts of NOAC
      treated mice was composed of unmetabolized NOAC, hydroxylated NOAC (NOAC + OH),
      its sulfated derivative (NOAC + OSO3H), and unidentified metabolites, whereas in
      urine, the hydrophilic molecules ara-C and ara-U were found. During the period of
      48 h only 2% of the injected NOAC was eliminated in its unmetabolized form,
      whereas 25% was identified as main metabolite ara-C. Urine collected during 48 h
      in ara-C-treated mice contained 33% of the injected dose as unmetabolized drug
      and 13% as the main metabolite ara-U. Thus, NOAC is metabolized by two major
      pathways, one leading to the hydrophilic metabolites ara-C and ara-U and the
      other to hydroxylated and sulfated NOAC.

PMID- 10064565
TI  - Glutathione conjugation of trichloroethylene in human liver and kidney: kinetics
      and individual variation.
AB  - Isolated human hepatocytes exhibited time-, trichloroethylene (Tri) concentration
      , and cell concentration-dependent formation of S-(1, 2-dichlorovinyl)glutathione
      (DCVG) in incubations in sealed flasks with 25 to 10,000 ppm Tri in the
      headspace, corresponding to 0.011 to 4.4 mM in hepatocytes. Maximal formation of
      DCVG (22.5 +/- 8.3 nmol/120 min per 10(6) cells) occurred with 500 ppm Tri. Time
      , protein concentration-, and both Tri and GSH concentration-dependent formation
      of DCVG were observed in liver and kidney subcellular fractions. Two kinetically
      distinct systems were observed in both cytosol and microsomes from pooled liver
      samples, whereas only one system was observed in subcellular fractions from
      pooled kidney samples. Liver cytosol exhibited apparent Km values (microM Tri) of
      333 and 22.7 and Vmax values (nmol DCVG formed/min per mg protein) of 8.77 and
      4.27; liver microsomes exhibited apparent Km values of 250 and 29.4 and Vmax
      values of 3.10 and 1.42; kidney cytosol and microsomes exhibited apparent Km
      values of 26.3 and 167, respectively, and Vmax values of 0.81 and 6.29,
      respectively. DCVG formation in samples of liver cytosol and microsomes from 20
      individual donors exhibited a 6.5-fold variation in microsomes but only a 2.4
      fold variation in cytosol. In coincubations of pooled liver cytosol and
      microsomes, addition of an NADPH-regenerating system produced marked inhibition
      of DCVG formation, but addition of GSH had no effect on cytochrome P-450
      catalyzed formation of chloral hydrate. These results indicate that both human
      kidney and liver have significant capacity to catalyze DCVG formation, indicating
      that the initial step of the GSH-dependent pathway is not limiting in the
      formation of nephrotoxic and nephrocarcinogenic metabolites.

PMID- 10064566
TI  - Cytochrome P-450 1A1 expression in human small bowel: interindividual variation
      and inhibition by ketoconazole.
AB  - Human cytochrome P-450 1A1 (CYP1A1) is located primarily in extrahepatic tissues.
      To begin the characterization of this enzyme in the small intestine, we screened
      a bank of 18 human small intestinal microsomal preparations for CYP1A1 catalytic
      [(7-ethoxyresorufin O-deethylase (EROD)] activity and protein content. Although
      EROD activity was below detectable limits in 12 of the preparations, 6 exhibited
      measurable activity (1.4-123.5 pmol/min/mg), some exceeding that for 2 human
      liver microsomal preparations (11.0 and 26.4 pmol/min/mg). This variation was not
      due to variable quality of the preparations because each sample displayed readily
      detectable CYP3A4 catalytic activity and immunoreactive protein. We inadvertently
      found that intestinal EROD activity was inhibitable by ketoconazole at a
      concentration commonly believed to selectively inhibit CYP3A4. The possibility
      that CYP3A4 metabolizes 7-ethoxyresorufin was excluded because there was no
      correlation between intestinal CYP3A4 catalytic and EROD activity, and cDNA
      expressed human CYP3A4 exhibited no EROD activity. Moreover, CYP1A1
      immunoreactive protein was most abundant in the three intestinal preparations
      with the highest EROD activities, and the mean apparent Ki of ketoconazole
      observed for these three preparations (40 nM) was essentially identical with that
      for cDNA-expressed human CYP1A1 (37 nM). In summary, there is large
      interindividual variation in CYP1A1 expression in human small bowel, and
      ketoconazole is not a selective CYP3A4 inhibitor in in vitro metabolism studies
      involving intestinal tissue obtained from some individuals. These observations
      raise the possibility that in vivo drug interactions involving ketoconazole could
      result from CYP1A1 inhibition in the intestine in some individuals.

PMID- 10064567
TI  - Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in
      human hepatocytes: identification of glutathione conjugated metabolites.
AB  - The nonsteroidal anti-inflammatory drug diclofenac causes a rare but potentially
      fatal hepatotoxicity that may be associated with the formation of reactive
      metabolites. In this study, three glutathione (GSH) adducts, namely 5-hydroxy-4
      (glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2),
      and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified by liquid
      chromatography-tandem mass spectrometry analysis of bile from Sprague-Dawley rats
      injected i.p. with a single dose of diclofenac (200 mg/kg). These adducts
      presumably were formed via hepatic cytochrome P-450 (CYP)-catalyzed oxidation of
      diclofenac to reactive benzoquinone imines that were trapped by GSH conjugation.
      In support of this hypothesis, M1, M2, and M3 were generated from diclofenac in
      incubations with rat liver microsomes in the presence of NADPH and GSH. Increases
      in adduct formation were observed when incubations were performed with liver
      microsomes from phenobarbital- or dexamethasone-treated rats. Adduct formation
      was inhibited by polyclonal antibodies against CYP2B, CYP2C, and CYP3A (40-50%
      inhibition at 5 mg of IgG/nmol of CYP) but not by an antibody against CYP1A.
      Maximal inhibition was obtained when the three inhibitory antibodies were used in
      a cocktail fashion (70-80% inhibition at 2.5 mg of each IgG/nmol of CYP). These
      data suggest that diclofenac undergoes biotransformation to reactive metabolites
      in rats and that CYP isoforms of the 2B, 2C, and 3A subfamilies are involved in
      this bioactivation process. With respect to CYP2C isoforms, rat hepatic CYP2C7
      and CYP2C11 were implicated as mediators of the bioactivation based on
      immunoinhibition studies using antibodies specific to CYP2C7 and CYP2C11.
      Screening for GSH adducts also was carried out in human hepatocyte cultures
      containing diclofenac, and M1, M2, and M3 again were detected. It is possible,
      therefore, that reactive benzoquinone imines may be formed in vivo in humans and
      contribute to diclofenac-mediated hepatic injury.

PMID- 10064568
TI  - Distribution kinetics of salicylic acid in the dual-perfused rat liver
      preparation.
AB  - The hepatic distribution kinetics of salicylic acid was determined using a single
      pass dual hepatic artery (HA) and portal vein (PV) perfused in situ rat liver
      preparation. Bolus doses of [14C]salicylic acid and of reference markers ([3H]
      water and [14C]-sucrose) were injected in a random order into either the HA or PV
      and then, after an appropriate interval, into the alternate vessel. The hepatic
      outflow profile of [14C]salicylic acid displayed a characteristic sharp peak
      followed by a slower eluting tail, whereas sucrose and water displayed unimodal
      outflow profiles. The biphasic outflow profile indicates that the hepatic
      distribution of salicylic acid is not instantaneous but is limited by a
      permeability barrier. The in situ permeability surface area product for
      [14C]salicylic acid was 3.35 +/- 0.26 ml/min/g for PV and 7.45 +/- 1. 50 ml/min/g
      for HA administration. Furthermore, theory dictates that hepatic uptake is
      influenced by both perfusion and permeability if effective permeability surface
      area product/blood flow ratio lies between the values of 0.06 and 7.0. Our
      estimates (3.0 for venous output and 6.7 for arterial input) indicate that
      hepatic uptake of salicylic acid is dependent on both perfusion and permeability.
      The volume terms were calculated using two different methods, standard and
      specific. Regardless of the compound and method, the volume of distribution after
      arterial administration was larger than that after venous administration. In
      addition, a volume of distribution approximately twice that of the total aqueous
      space (i.e., HA, 2.23 +/- 0.13 versus 1.10 +/- 0.07 ml/g; PV, 1.72 +/- 0.16
      versus 0.68 +/- 0.04 ml/g) implies that salicylic acid has a significant affinity
      for hepatic tissue. A similar tissue-to-perfusate partition coefficient
      associated with HA and PV input (5.40 +/- 0.38 versus 6. 48 +/- 0.56) indicates
      that affinity of salicylic acid for hepatic tissue is independent of the route of
      input.

PMID- 10064569
TI  - Induction of CYP1A2 by phenobarbital in the livers of aryl hydrocarbon-responsive
      and -nonresponsive mice.
AB  - The effects of phenobarbital treatment on the expression of the cytochrome P-450
      (CYP or P-450) enzyme CYP1A2 in the livers of mice of various strains were
      examined. Phenobarbital induced the expression of CYP1A2 at the levels of mRNA,
      protein, and enzyme activity (methoxyresorufin O-demethylation and metabolic
      activation of 2-amino-3-methylimidazo[4,5-f]quinoline) in both aryl hydrocarbon
      responsive [C57BL/6NCrj (C57BL/6), C3H/HeJSlc] and -nonresponsive (DBA/2NCrj,
      AKR/JSea, NZB/NSlc) mouse strains. The induction of CYP2B10, which is known as a
      phenobarbital-inducible P-450 in mice, was prominent in the livers of all five
      strains examined, whereas clear inductive effects on the P-450 CYP2B9 were not
      observed in female C57BL/6 and female DBA/2NCrj mice. These results indicate that
      CYP1A2 is a member of the family of phenobarbital-inducible genes in mice and
      suggest that the aryl hydrocarbon receptor-dependent induction pathway is not
      involved in the induction of CYP1A2. This concept is in accordance with those
      proposed by other laboratories recently using the AhR knockout mice. The
      following are new observations of this report. The magnitude of the increases in
      the CYP1A2 mRNA, protein, and enzyme activities were comparable among these three
      levels (ranging from 1.4- to 3. 1-fold), suggesting that the induction of CYP1A2
      by phenobarbital is mainly determined at a pretranslational level. Cyclobarbital,
      pentobarbital, and secobarbital also induced CYP1A2 mRNA in primary culture
      hepatocytes from C57BL/6 mice. Barbital, in contrast, did not show any clear
      inductive effect on CYP1A2 mRNA.

PMID- 10064570
TI  - G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese.
AB  - The molecular basis of the reduced ability of a Chinese to metabolize
      debrisoquine was explored by sequencing all of the nine exons of the CYP2D6 gene.
      The subject has T188, A1846, T2938, and C4268 (CYP2D6*14) instead of C188, G1846,
      C2938, and G4268 as in wild-type subjects. XbaI restriction fragment length
      polymorphism indicated that the subject has a 29-kb allele and a gene deletion
      (11.5 kb) in another allele (CYP2D6*5). A CYP2D6*14 allele together with a
      CYP2D6*5 allele may cause the poor metabolism of the subject. T188, T2938, and
      C4268 are common haplotypes in Chinese-extensive metabolizers. The effect of
      G1846 to A mutation in CYP2D6 metabolism has not been reported. A polymerase
      chain reaction-based endonuclease digestion test was designed for the G/N1846
      polymorphism and 124 Chinese subjects were screened. With DNA sequencing, two
      other subjects showed the heterozygous G/A1846 and have a relatively high
      metabolic ratio of debrisoquine hydroxylation. The site-directed mutagenesis was
      used to create recombinant CYP2D6 cDNA with T188, A1846, or C4268. The cDNA was
      then transfected into Rat-1 cells. The transfection was confirmed by Southern,
      Northern, and Western blots. Based on the same microsomal protein level, the
      bufuralol 1'-hydroxylation activity of CYP2D6(T188) or CYP2D6(A1846) was
      significantly lower than that of the wild-type CYP2D6. P34S mutation (C188 to T)
      significantly decreased CYP2D6 activity. G169R mutation (G1846 to A) also
      decreased CYP2D6 activity and may further reduce the metabolic activity of CYP2D6
      protein with P34S, R296C, and S486T mutations.

PMID- 10064571
TI  - The aromatase inactivator 4-hydroxyandrostenedione (4-OH-A) inhibits tamoxifen
      metabolism by rat hepatic cytochrome P-450 3A: potential for drug-drug
      interaction of tamoxifen and 4-OH-A in combined anti-breast cancer therapy.
AB  - Tamoxifen (tam), an anti-breast cancer agent, is metabolized into tam-N-oxide by
      the hepatic flavin-containing monooxygenase and into N-desmethyl- and 4-hydroxy
      tam by cytochrome P-450s (CYPs). Additionally, tam is metabolically activated by
      hepatic CYP3A, forming a reactive intermediate that binds covalently to proteins.
      Tam and 4-hydroxyandrostenedione (4-OH-A) are currently used to treat breast
      cancer, and it has been contemplated that 4-OH-A be given concurrently with tam
      to contravene potential tumor resistance to tam. Because alterations in tam
      metabolism may influence its therapeutic efficacy, the effect of 4-OH-A on tam
      metabolism was examined. Incubation of tam with liver microsomes from
      phenobarbital-treated rats, in the presence of 4-OH-A (10-100 microM), resulted
      in marked inhibition of tam-N-demethylation and tam covalent binding and in
      decreased tam-N-oxide accumulation; however, there was no inhibition of the
      formation of 4-hydroxy-tam and of 3,4-dihydroxytamoxifen. These findings indicate
      that 4-OH-A inhibits CYP3A, but not P-450(s) that catalyze tam 4-hydroxylation.
      The diminished tam-N-oxide accumulation could be due to decreased N-oxide
      formation and/or due to increased N-oxide reduction. Incubation of tam-N-oxide
      with liver microsomes containing heat-inactivated flavin-containing monooxygenase
      demonstrated that 4-OH-A increases the accumulation of tam, possibly by
      diminishing its P-450-mediated metabolism. Kinetic studies indicate that 4-OH-A
      is a competitive inhibitor of CYP3A, but not a time-dependent inactivator.
      Consequently, the concurrent treatment of tam and 4-OH-A may result in increased
      tam half-life and thus could potentiate the therapeutic efficacy of tam and
      diminish the potential side effects of tam by inhibiting its covalent binding to
      proteins and possibly to DNA.

PMID- 10064572
TI  - Quantitative prediction of metabolic inhibition of midazolam by itraconazole and
      ketoconazole in rats: implication of concentrative uptake of inhibitors into
      liver.
AB  - To evaluate the extent of drug-drug interaction concerning metabolic inhibition
      in the liver quantitatively, we tried to predict the plasma concentration
      increasing ratio of midazolam (MDZ) by itraconazole (ITZ) or ketoconazole (KTZ)
      in rats. MDZ was administered at a dose of 10 mg/kg through the portal vein at 60
      min after bolus administration of 20 mg/kg ITZ or during 0.33 mg/h/body of KTZ
      infusion. The ratio values in the area under the plasma concentration curve of
      MDZ in the presence of ITZ and KTZ was 2.14 and 1.67, respectively. The liver
      unbound concentration to plasma-unbound concentration ratios of ITZ and KTZ were
      11 approximately 14 and 1.3, respectively, suggesting a concentrative uptake of
      both drugs into the liver. ITZ and KTZ competitively inhibited the oxidative
      metabolism of MDZ in rat liver microsomes, and Ki values of ITZ and KTZ were 0.23
      microM and 0.16 microM, respectively. We predicted the ratio values of MDZ in the
      presence of ITZ and KTZ, using Ki values and unbound concentrations of both drugs
      in the plasma or liver. The predicted ratio values in the presence of ITZ or KTZ
      calculated by using unbound concentration in the plasma were 1.03 approximately
      1.05 and 1.39, whereas those calculated using unbound concentration in the liver
      were 1.73 approximately 1.97 and 1.51, respectively, which were very close to the
      observed ratio values. These findings indicated the necessity to consider the
      concentrative uptake of inhibitors into the liver for the quantitative prediction
      of the drug-drug interactions concerning metabolic inhibition in the liver.

PMID- 10064573
TI  - Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2
      inhibitor.
AB  - The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated
      in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was
      found to be 10 to 20 times more soluble than DFU in a variety of aqueous
      vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax
      of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s
      of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced
      pyresis assays in rats are comparable with the ED50s observed when dosing with
      DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that
      the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing
      pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with
      subcellular fractions from rat liver indicated that most of the oxidation of DFU
      lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol
      can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the
      incubations. Fractionation of human liver cytosolic proteins showed that at least
      three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to
      DFU. Incubations with commercially available dehydrogenases suggest that alcohol
      and hydroxysteroid dehydrogenases are involved in this oxidative process. These
      data together suggest that lactols may represent useful prodrugs for lactone
      containing drugs.

PMID- 10064574
TI  - The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect
      on human cytochrome P-450 and implications for metabolic drug interactions.
AB  - Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was
      metabolized by human liver microsomes to 5-hydroxy-, 6-hydroxy-, and N
      deisopropyl-fluvastatin. Total metabolite formation was biphasic with apparent Km
      values of 0.2 to 0.7 and 7.9 to 50 microM and intrinsic metabolic clearance rates
      of 1.4 to 4 and 0.3 to 1.5 ml/h/mg microsomal protein for the high and low Km
      components, respectively. Several enzymes, but mainly CYP2C9, catalyzed
      fluvastatin metabolism. Only CYP2C9 inhibitors such as sulfaphenazole inhibited
      the formation of both 6-hydroxy- and N-deisopropyl-fluvastatin. 5-Hydroxy
      fluvastatin formation was reduced by compounds that are inhibitors of CYP2C9,
      CYP3A, or CYP2C8. Fluvastatin in turn inhibited CYP2C9-catalyzed tolbutamide and
      diclofenac hydroxylation with Ki values of 0.3 and 0.5 microM, respectively. For
      CYP2C8-catalyzed 6alpha-hydroxy-paclitaxel formation the IC50 was 20 microM and
      for CYP1A2, CYP2C19, and CYP3A catalyzed reactions, no IC50 could be determined
      up to 100 microM fluvastatin. All three fluvastatin metabolites were also formed
      by recombinant CYP2C9, whereas CYP1A1, CYP2C8, CYP2D6, and CYP3A4 produced only 5
      hydroxy-fluvastatin. Km values were approximately 1, 2.8, and 7.1 microM for
      CYP2C9, CYP2C8, and CYP3A, respectively. No difference in fluvastatin metabolism
      was found between the CYP2C9R144 and CYP2C9C144 alleles, suggesting the absence
      of polymorphic fluvastatin metabolism by these alleles. CYP1A2, CYP2A6, CYP2B6,
      CYP2C19, CYP2E1, and CYP3A5 did not produce detectable amounts of any metabolite.
      This data indicates that several human cytochrome P-450 enzymes metabolize
      fluvastatin with CYP2C9 contributing 50-80%. Any coadministered drug would
      therefore only partially reduce the metabolic clearance of fluvastatin;
      therefore, the likelihood for serious metabolic drug interactions is expected to
      be minimal.

PMID- 10064575
TI  - The effect of fluconazole on cyclophosphamide metabolism in children.
AB  - Fluconazole is increasingly used in children receiving chemotherapy. Many of
      these patients are being treated with cyclophosphamide, which must undergo
      hepatic metabolism to produce active alkylating species. As a consequence of the
      cytochrome P-450 inhibitory properties of fluconazole, a potential interaction
      exists between these two agents that could influence the therapeutic effect of
      cyclophosphamide. To investigate this interaction, a retrospective case series of
      patients was chosen from a population of children with a previously established
      profile of cyclophosphamide metabolism. Twenty-two children who were not
      receiving other therapy known to influence drug metabolism were selected and
      analyzed in terms of fluconazole treatment; of these, nine were receiving
      fluconazole and thirteen were identified as controls. Study design was not
      randomized. The plasma clearance of cyclophosphamide was lower in patients
      receiving fluconazole [mean(SD) 2.4(0.71) versus 4.2(1.2) l/h/m2, p =.001]. In
      vitro studies were performed to characterize the interaction between fluconazole
      and cyclophosphamide in six human liver microsomes. The concentration of
      fluconazole required to reduce the production of 4-hydroxycyclophosphamide to 50%
      of control values (IC50) varied between 9 and 80 microM (median 38 microM).
      Further studies of the effect of fluconazole on 4-hydroxycyclophosphamide
      production in vivo are warranted to determine whether this interaction reduces
      the therapeutic effect of cyclophosphamide in clinical practice.

PMID- 10064576
TI  - Aldehyde oxidase-dependent marked species difference in hepatic metabolism of the
      sedative-hypnotic, zaleplon, between monkeys and rats.
AB  - A marked difference in hepatic activity of aldehyde oxidase between rats and
      monkeys was found to be responsible for the previously reported marked species
      difference in the metabolism of Zaleplon in vivo. In the postmitochondrial
      fractions, S-9s, from liver homogenates of these animals, Zaleplon was
      transformed in the presence of NADPH into the side chain oxidation product, N
      desethyl-Zaleplon, and the aromatic ring oxidation product, 5-oxo-Zaleplon. In
      the rat S-9, N-desethyl-Zaleplon and 5-oxo-Zaleplon were a major and a very minor
      metabolites, respectively. However, in the monkey S-9, Zaleplon was transformed
      into 5-oxo-Zaleplon at a much higher rate than that for N-desethyl-Zaleplon
      formation. N-Desethyl-Zaleplon was formed in the monkey S-9 at a rate almost
      equal to that in the rat S-9. N-Desethyl-5-oxo-Zaleplon was formed at a minor
      rate only in the monkey S-9 through N-desethyl-Zaleplon as an obligatory
      intermediate. The hepatic activity for the formation of 5-oxo-Zaleplon in the
      monkey and rat was localized in cytosol and did not require NADPH. Sensitivity to
      various inhibitors and requirement of water as oxygen source, using H218O,
      strongly suggested that the hepatic cytosolic formation of 5-oxo-Zaleplon was
      mediated by aldehyde oxidase. N-Desethyl-Zaleplon was formed in the presence of
      NADPH by microsomes from the liver of rats and monkeys, and its formation was
      strongly suggested using various cytochrome P-450 inhibitors to be mediated by a
      number of cytochrome P-450 isoforms, such as 3A, 2C, and 2D subfamilies.

PMID- 10064577
TI  - Crystal structure of the soluble form of the human fcgamma-receptor IIb: a new
      member of the immunoglobulin superfamily at 1.7 A resolution.
AB  - Fcgamma-receptors (FcgammaRs) represent the link between the humoral and cellular
      immune responses. Via the binding to FcgammaR-positive cells, immunocomplexes
      trigger several functions such as endocytosis, antibody-dependent cell-mediated
      cytotoxity (ADCC) and the release of mediators, making them a valuable target for
      the modulation of the immune system. We solved the crystal structure of the
      soluble human Fcgamma-receptor IIb (sFcgammaRIIb) to 1.7 A resolution. The
      structure reveals two typical immunoglobulin (Ig)-like domains enclosing an angle
      of approximately 70 degrees, leading to a heart-shaped overall structure. In
      contrast to the observed flexible arrangement of the domains in other members of
      the Ig superfamily, the two domains are anchored by several hydrogen bonds. The
      structure reveals that the residues relevant for IgG binding, which were already
      partially characterized by mutagenesis studies, are located within the BC, C'E
      and FG loops between the beta-strands of the second domain. Moreover, we discuss
      a model for the sFcgammaRIIb:IgG complex. In this model, two FcgammaR molecules
      bind one IgG molecule with their second domains, while the first domain points
      away from the complex and is therefore available for binding other cell surface
      molecules, by which potential immunosuppressing functions could be mediated.

PMID- 10064578
TI  - Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a
      component of the deoxyribonucleoside triphosphate-synthesizing complex.
AB  - Bacteriophage T4 deoxycytidylate hydroxymethylase (EC 2.1.2.8), a homodimer of
      246-residue subunits, catalyzes hydroxymethylation of the cytosine base in
      deoxycytidylate (dCMP) to produce 5-hydroxymethyl-dCMP. It forms part of a phage
      DNA protection system and appears to function in vivo as a component of a
      multienzyme complex called deoxyribonucleoside triphosphate (dNTP) synthetase. We
      have determined its crystal structure in the presence of the substrate dCMP at
      1.6 A resolution. The structure reveals a subunit fold and a dimerization pattern
      in common with thymidylate synthases, despite low (approximately 20%) sequence
      identity. Among the residues that form the dCMP binding site, those interacting
      with the sugar and phosphate are arranged in a configuration similar to the
      deoxyuridylate binding site of thymidylate synthases. However, the residues
      interacting directly or indirectly with the cytosine base show a more divergent
      structure and the presumed folate cofactor binding site is more open. Our
      structure reveals a water molecule properly positioned near C-6 of cytosine to
      add to the C-7 methylene intermediate during the last step of hydroxymethylation.
      On the basis of sequence comparison and crystal packing analysis, a hypothetical
      model for the interaction between T4 deoxycytidylate hydroxymethylase and T4
      thymidylate synthase in the dNTP-synthesizing complex has been built.

PMID- 10064579
TI  - Structure of DNA-dependent protein kinase: implications for its regulation by
      DNA.
AB  - DNA double-strand breaks are created by ionizing radiation or during V(D)J
      recombination, the process that generates immunological diversity. Breaks are
      repaired by an end-joining reaction that requires DNA-PKCS, the catalytic subunit
      of DNA-dependent protein kinase. DNA-PKCS is a 460 kDa serine-threonine kinase
      that is activated by direct interaction with DNA. Here we report its structure at
      22 A resolution, as determined by electron crystallography. The structure
      contains an open channel, similar to those seen in other double-stranded DNA
      binding proteins, and an enclosed cavity with three openings large enough to
      accommodate single-stranded DNA, with one opening adjacent to the open channel.
      Based on these structural features, we performed biochemical experiments to
      examine the interactions of DNA-PKCS with different DNA molecules. Efficient
      kinase activation required DNA longer than 12 bp, the minimal length of the open
      channel. Competition experiments demonstrated that DNA-PKCS binds to double- and
      single-stranded DNA via separate but interacting sites. Addition of unpaired
      single strands to a double-stranded DNA fragment stimulated kinase activation.
      These results suggest that activation of the kinase involves interactions with
      both double- and single-stranded DNA, as suggested by the structure. A model for
      how the kinase is regulated by DNA is described.

PMID- 10064580
TI  - Head-to-tail dimers and interdomain flexibility revealed by the crystal structure
      of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab.
AB  - The crystal structure of an intact molecule of HIV-1 capsid protein (p24) in
      complex with a monoclonal antibody fragment recognizing an epitope on the C
      terminal domain has been determined at 3 A resolution. The helical N- and C
      terminal domains of p24 are linked by an extended peptide forming a flexibly
      linked dumb-bell-shaped molecule 75 A in overall length. The p24 construct used
      is a variant with an N-terminal extension that mimics to some extent the Gag
      context of p24. We observed a novel head-to-tail dimer of p24 molecules which
      occurs through the formation of a substantial intermolecular interface between
      the N- and C-terminal domains. Comparison with previously observed p24 dimers
      shows that the same residues and secondary structural elements can partake in
      different interfaces revealing a remarkable stickiness and plasticity of the p24
      molecule, properties which, combined with the inter-domain flexibility, are
      presumably important in the assembly and maturation of viral particles. Previous
      mutagenesis studies designed to test specific N-N and C-C homodimer interfaces do
      not discriminate fully against the possibility of the observed N-C interface.

PMID- 10064581
TI  - Physical interactions among circadian clock proteins KaiA, KaiB and KaiC in
      cyanobacteria.
AB  - The kai gene cluster, which is composed of three genes, kaiA, kaiB and kaiC, is
      essential for the generation of circadian rhythms in the unicellular
      cyanobacterium Synechococcus sp. strain PCC 7942. Here we demonstrate the direct
      association of KaiA, KaiB and KaiC in yeast cells using the two-hybrid system, in
      vitro and in cyanobacterial cells. KaiC enhanced KaiA-KaiB interaction in vitro
      and in yeast cells, suggesting that the three Kai proteins were able to form a
      heteromultimeric complex. We also found that a long period mutation kaiA1
      dramatically enhanced KaiA-KaiB interaction in vitro. Thus, direct protein
      protein association among the Kai proteins may be a critical process in the
      generation of circadian rhythms in cyanobacteria.

PMID- 10064582
TI  - Car: a cytoplasmic sensor responsible for arginine chemotaxis in the archaeon
      Halobacterium salinarum.
AB  - A new metabolic signaling pathway for arginine, both a chemoeffector and a
      fermentative energy source, is described for Halobacterium salinarum. Systematic
      screening of 80+ potentially chemotactic compounds with two behavioral assays
      identified leucine, isoleucine, valine, methionine, cysteine, arginine and
      several peptides as strong chemoattractants. Deletion analysis of a number of
      potential halobacterial transducer genes led to the identification of Car, a
      specific cytoplasmic arginine transducer which lacks transmembrane helices and
      was biochemically shown to be localized in the cytoplasm. Flow assays were used
      to show specific adaptive responses to arginine and ornithine in wild-type but
      not Deltacar cells, demonstrating the role of Car in sensing arginine. The
      signaling pathway from external arginine to the flagellar motor of the cell
      involves an arginine:ornithine antiporter which was quantitatively characterized
      for its transport kinetics and inhibitors. By compiling the chemotactic behavior,
      the adaptive responses and the characteristics of the arginine:ornithine
      antiporter to arginine and its analogs, we now understand how the combination of
      arginine uptake and its metabolic conversion is required to build an effective
      sensing system. In both bacteria and the archaea this is the first chemoeffector
      molecule of a soluble methylatable transducer to be identified.

PMID- 10064583
TI  - The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and
      Eps15.
AB  - Clathrin-mediated endocytosis is a multistep process which requires interaction
      between a number of conserved proteins. We have cloned two mammalian genes which
      code for a number of endocytic adaptor proteins. Two of these proteins, termed
      Ese1 and Ese2, contain two N-terminal EH domains, a central coiled-coil domain
      and five C-terminal SH3 domains. Ese1 is constitutively associated with Eps15
      proteins to form a complex with at least 14 protein-protein interaction surfaces.
      Yeast two-hybrid assays have revealed that Ese1 EH and SH3 domains bind epsin
      family proteins and dynamin, respectively. Overexpression of Ese1 is sufficient
      to block clathrin-mediated endocytosis in cultured cells, presumably through
      disruption of higher order protein complexes, which are assembled on the
      endogenous Ese1-Eps15 scaffold. The Ese1-Eps15 scaffold therefore links dynamin,
      epsin and other endocytic pathway components.

PMID- 10064584
TI  - Telomere shortening in mTR-/- embryos is associated with failure to close the
      neural tube.
AB  - Mice genetically deficient for the telomerase RNA (mTR) can be propagated for
      only a limited number of generations. In particular, mTR-/- mice of a mixed
      C57BL6/129Sv genetic background are infertile at the sixth generation and show
      serious hematopoietic defects. Here, we show that a percentage of mTR-/- embryos
      do not develop normally and fail to close the neural tube, preferentially at the
      forebrain and midbrain. The penetrance of this defect increases with the
      generation number, with 30% of the mTR-/- embryos from the fifth generation
      showing the phenotype. Moreover, mTR-/- kindreds in a pure C57BL6 background are
      only viable up to the fourth generation and also show defects in the closing of
      the neural tube. Cells derived from mTR-/- embryos that fail to close the neural
      tube have significantly shorter telomeres and decreased viability than their mTR
      /- littermates with a closed neural tube, suggesting that the neural tube defect
      is a consequence of the loss of telomere function. The fact that the main defect
      detected in mTR-/- embryos is in the closing of the neural tube, suggests that
      this developmental process is among the most sensitive to telomere loss and
      chromosomal instability.

PMID- 10064585
TI  - The yeast non-Mendelian factor [ETA+] is a variant of [PSI+], a prion-like form
      of release factor eRF3.
AB  - The yeast non-Mendelian factor [ETA+] is lethal in the presence of certain
      mutations in the SUP35 and SUP45 genes, which code for the translational release
      factors eRF3 and eRF1, respectively. One such mutation, sup35-2, is now shown to
      contain a UAG stop codon prior to the essential region of the gene. The non
      Mendelian inheritance of [ETA+] is reminiscent of the yeast [PSI+] element, which
      is due to a self-propagating conformation of Sup35p. Here we show that [ETA+] and
      [PSI+] share many characteristics. Indeed, like [PSI+], the maintenance of [ETA+]
      requires the N-terminal region of Sup35p and depends on an appropriate level of
      the chaperone protein Hsp104. Moreover, [ETA+] can be induced de novo by excess
      Sup35p, and [ETA+] cells have a weak nonsense suppressor phenotype characteristic
      of weak [PSI+]. We conclude that [ETA+] is actually a weak, unstable variant of
      [PSI+]. We find that although some Sup35p aggregates in [ETA+] cells, more Sup35p
      remains soluble in [ETA+] cells than in isogenic strong [PSI+] cells. Our data
      suggest that the amount of soluble Sup35p determines the strength of
      translational nonsense suppression associated with different [PSI+] variants.

PMID- 10064586
TI  - Respiratory chain strongly oxidizes the CXXC motif of DsbB in the Escherichia
      coli disulfide bond formation pathway.
AB  - Escherichia coli DsbB has four essential cysteine residues, among which Cys41 and
      Cys44 form a CXXC redox active site motif and the Cys104-Cys130 disulfide bond
      oxidizes the active site cysteines of DsbA, the disulfide bond formation factor
      in the periplasm. Functional respiratory chain is required for the cell to keep
      DsbA oxidized. In this study, we characterized the roles of essential cysteines
      of DsbB in the coupling with the respiratory chain. Cys104 was found to form the
      inactive complex with DsbA under respiration-defective conditions. While DsbB,
      under normal aerobic conditions, is in the oxidized state, having two
      intramolecular disulfide bonds, oxidation of Cys104 and Cys130 requires the
      presence of Cys41-Cys44. Remarkably, the Cys41-Cys44 disulfide bond is refractory
      to reduction by a high concentration of dithiothreitol, unless the membrane is
      solubilized with a detergent. This reductant resistance requires both the
      respiratory function and oxygen, since Cys41-Cys44 became sensitive to the
      reducing agent when membrane was prepared from quinone- or heme-depleted cells or
      when a membrane sample was deaerated. Thus, the Cys41-Val-Leu-Cys44 motif of DsbB
      is kept both strongly oxidized and strongly oxidizing when DsbB is integrated
      into the membrane with the normal set of respiratory components.

PMID- 10064587
TI  - A region of the Yersinia pseudotuberculosis invasin protein enhances integrin
      mediated uptake into mammalian cells and promotes self-association.
AB  - Invasin allows efficient entry into mammalian cells by Yersinia
      pseudotuberculosis. It has been shown that the C-terminal 192 amino acids of
      invasin are essential for binding of beta1 integrin receptors and subsequent
      uptake. By analyzing the internalization of latex beads coated with invasin
      derivatives, an additional domain of invasin was shown to be required for
      efficient bacterial internalization. A monomeric derivative encompassing the C
      terminal 197 amino acids was inefficient at promoting entry of latex beads,
      whereas dimerization of this derivative by antibody significantly increased
      uptake. By using the DNA-binding domain of lambda repressor as a reporter for
      invasin self-interaction, we have demonstrated that a region of the invasin
      protein located N-terminal to the cell adhesion domain of invasin is able to self
      associate. Chemical cross-linking studies of purified and surface-exposed invasin
      proteins, and the dominant-interfering effect of a non-functional invasin
      derivative are consistent with the presence of a self-association domain that is
      located within the region of invasin that enhances bacterial uptake. We conclude
      that interaction of homomultimeric invasin with multiple integrins establishes
      tight adherence and receptor clustering, thus providing a signal for
      internalization.

PMID- 10064588
TI  - Translocation of ornithine decarboxylase to the surface membrane during cell
      activation and transformation.
AB  - Ornithine decarboxylase (ODC) is highly up-regulated in proliferating and
      transforming cells. Here we show that upon induction, an initial cytosolic
      increase of ODC is followed by translocation of a fraction of the enzyme to the
      surface membrane. ODC membrane translocation is mediated by a p47(phox) membrane
      targeting motif-related sequence, as indicated by reduced ODC activity in the
      membrane fraction of cells treated with a competing, ODC-derived (amino acids 165
      172) peptide, RLSVKFGA, which is homologous to the p47(phox) membrane-targeting
      sequence. p47(phox) membrane translocation is known to be dependent on the
      phosphorylation of the targeting motif. Analogously, overexpressed ODC.S167A, a
      mutant ODC lacking the putative phosphorylation site Ser67, is unable to move to
      the surface membrane. Cells blocked with the RLSVKFGA peptide showed defective
      transformation, indicating that the motif-mediated translocation of ODC is
      prerequisite to its biological function. Constitutive targeting of ODC to the
      membrane using a plasmid encoding the chimeric protein, wild-type ODC with C
      terminal linkage to the farnesylation motif of K-ras, caused impaired cytokinesis
      with an accumulation of polykaryotic cells. Impaired cytokinesis confirms that
      ODC is involved in mitotic cytoskeletal rearrangement events and pinpoints the
      importance of relevant membrane targeting to its physiological function.

PMID- 10064589
TI  - Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic
      differentiation.
AB  - p21(Cip1/WAF1) inhibits cell-cycle progression by binding to G1 cyclin/CDK
      complexes and proliferating cell nuclear antigen (PCNA) through its N- and C
      terminal domains, respectively. The cell-cycle inhibitory activity of
      p21(Cip1/WAF1) is correlated with its nuclear localization. Here, we report a
      novel cytoplasmic localization of p21(Cip1/WAF1) in peripheral blood monocytes
      (PBMs) and in U937 cells undergoing monocytic differentiation by in vitro
      treatment with vitamin D3 or ectopic expression of p21(Cip1/WAF1), and analyze
      the biological consequences of this cytoplasmic expression. U937 cells which
      exhibit nuclear p21(Cip1/WAF1) demonstrated G1 cell-cycle arrest and subsequently
      differentiated into monocytes. The latter event was associated with a cytoplasmic
      expression of nuclear p21(Cip1/WAF1), concomitantly with a resistance to various
      apoptogenic stimuli. Biochemical analysis showed that cytoplasmic p21(Cip1/WAF1)
      forms a complex with the apoptosis signal-regulating kinase 1 (ASK1) and inhibits
      stress-activated MAP kinase cascade. Expression of a deletion mutant of
      p21(Cip1/WAF1) lacking the nuclear localization signal (DeltaNLS-p21) did not
      induce cell cycle arrest nor monocytic differentiation, but led to an apoptosis
      resistant phenotype, mediated by binding to and inhibition of the stress
      activated ASK1 activity. Thus, cytoplasmic p21(Cip1/WAF1) itself acted as an
      inhibitor of apoptosis. Our findings highlight the different functional roles of
      p21(Cip1/WAF1), which are determined by its intracellular distribution and are
      dependent on the stage of differentiation.

PMID- 10064590
TI  - Increased neurodegeneration during ageing in mice lacking high-affinity nicotine
      receptors.
AB  - We have examined neuroanatomical, biochemical and endocrine parameters and
      spatial learning in mice lacking the beta2 subunit of the nicotinic acetylcholine
      receptor (nAChR) during ageing. Aged beta2(-/-) mutant mice showed region
      specific alterations in cortical regions, including neocortical hypotrophy, loss
      of hippocampal pyramidal neurons, astro- and microgliosis and elevation of serum
      corticosterone levels. Whereas adult mutant and control animals performed well in
      the Morris maze, 22- to 24-month-old beta2(-/-) mice were significantly impaired
      in spatial learning. These data show that beta2 subunit-containing nAChRs can
      contribute to both neuronal survival and maintenance of cognitive performance
      during ageing. beta2(-/-) mice may thus serve as one possible animal model for
      some of the cognitive deficits and degenerative processes which take place during
      physiological ageing and in Alzheimer's disease, particularly those associated
      with dysfunction of the cholinergic system.

PMID- 10064591
TI  - Fast inactivation of a brain K+ channel composed of Kv1.1 and Kvbeta1.1 subunits
      modulated by G protein beta gamma subunits.
AB  - Modulation of A-type voltage-gated K+ channels can produce plastic changes in
      neuronal signaling. It was shown that the delayed-rectifier Kv1.1 channel can be
      converted to A-type upon association with Kvbeta1.1 subunits; the conversion is
      only partial and is modulated by phosphorylation and microfilaments. Here we show
      that, in Xenopus oocytes, expression of Gbeta1gamma2 subunits concomitantly with
      the channel (composed of Kv1.1 and Kvbeta1.1 subunits), but not after the
      channel's expression in the plasma membrane, increases the extent of conversion
      to A-type. Conversely, scavenging endogenous Gbetagamma by co-expression of the C
      terminal fragment of the beta-adrenergic receptor kinase reduces the extent of
      conversion to A-type. The effect of Gbetagamma co-expression is occluded by
      treatment with dihydrocytochalasin B, a microfilament-disrupting agent shown
      previously by us to enhance the extent of conversion to A-type, and by
      overexpression of Kvbeta1.1. Gbeta1gamma2 subunits interact directly with GST
      fusion fragments of Kv1.1 and Kvbeta1.1. Co-expression of Gbeta1gamma2 causes co
      immunoprecipitation with Kv1.1 of more Kvbeta1.1 subunits. Thus, we suggest that
      Gbeta1gamma2 directly affects the interaction between Kv1.1 and Kvbeta1.1 during
      channel assembly which, in turn, disrupts the ability of the channel to interact
      with microfilaments, resulting in an increased extent of A-type conversion.

PMID- 10064592
TI  - MAP kinase and cAMP filamentation signaling pathways converge on the unusually
      large promoter of the yeast FLO11 gene.
AB  - In Saccharomyces cerevisiae, two major signal transduction pathways, the Kss1
      MAPK pathway and the cAMP-regulated pathway, are critical for the differentiation
      of round yeast form cells to multicellular, invasive pseudohyphae. Here we report
      that these parallel pathways converge on the promoter of a gene, FLO11, which
      encodes a cell surface protein required for pseudohyphal formation. The FLO11
      promoter is unusually large, containing at least four upstream activation
      sequences (UASs) and nine repression elements which together span at least 2.8
      kb. Several lines of evidence indicate that the MAPK and cAMP signals are
      received by distinct transcription factors and promoter elements. First,
      regulation via the MAPK pathway requires the transcription factors Ste12p/Tec1p,
      whereas cAMP-mediated activation requires a distinct factor, Flo8p. Secondly,
      mutations in either pathway block FLO11 transcription. Overexpression of STE12
      can suppress the loss of FLO8, and overexpression of FLO8 can suppress the loss
      of STE12. Finally, multiple distinct promoter regions of the FLO11 promoter are
      required for its activation by either Flo8p or Ste12p/ Tec1p. Thus, like the
      promoters of the key developmental genes, HO and IME1, the FLO11 promoter is
      large and complex, endowing it with the ability to integrate multiple inputs.

PMID- 10064593
TI  - Activation of the Raf/MAP kinase cascade by the Ras-related protein TC21 is
      required for the TC21-mediated transformation of NIH 3T3 cells.
AB  - TC21 is a member of the Ras superfamily of small GTP-binding proteins and, like
      Ras, has been implicated in the regulation of growth-stimulating pathways. Point
      mutations introduced into TC21 based on equivalent H-Ras oncogenic mutations are
      transforming in cultured cells, and oncogenic mutations in TC21 have been
      isolated from several human tumours. The mechanism of TC21 signalling in
      transformation is poorly understood. While activation of the serine/threonine
      kinases Raf-1 and B-Raf has been implicated in signalling pathways leading to
      transformation by H-Ras, it has been argued that TC21 does not activate Raf-1 or
      B-Raf. Since the Raf-signalling pathway is important in transformation by other
      Ras proteins, we assessed whether the Raf pathway is important to transformation
      by TC21. Raf-1 and B-Raf are constitutively active in TC21-transformed cells and
      the ERK/MAPK cascade is required for the maintenance of the transformed state. We
      demonstrate that oncogenic V23 TC21, like Ras, interacts with Raf-1 and B-Raf
      (but not with A-Raf), resulting in the translocation of the Raf proteins to the
      plasma membrane and in their activation. Furthermore, using point mutations in
      the effector loop of TC21, we show that the interaction of TC21 with Raf-1 is
      crucial for transformation.

PMID- 10064594
TI  - Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished
      T cell responsiveness to TGF-beta.
AB  - SMAD3 is one of the intracellular mediators that transduces signals from
      transforming growth factor-beta (TGF-beta) and activin receptors. We show that
      SMAD3 mutant mice generated by gene targeting die between 1 and 8 months due to a
      primary defect in immune function. Symptomatic mice exhibit thymic involution,
      enlarged lymph nodes, and formation of bacterial abscesses adjacent to mucosal
      surfaces. Mutant T cells exhibit an activated phenotype in vivo, and are not
      inhibited by TGF-beta1 in vitro. Mutant neutrophils are also impaired in their
      chemotactic response toward TGF-beta. Chronic intestinal inflammation is
      infrequently associated with colonic adenocarcinoma in mice older than 6 months
      of age. These data suggest that SMAD3 has an important role in TGF-beta-mediated
      regulation of T cell activation and mucosal immunity, and that the loss of these
      functions is responsible for chronic infection and the lethality of Smad3-null
      mice.

PMID- 10064595
TI  - Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for
      the regulation of lipid kinases in vitro and in vivo.
AB  - Phosphoinositide 3-kinases (PI3Ks) are lipid kinases which also possess an in
      vitro protein kinase activity towards themselves or their adaptor proteins. The
      physiological relevance of these phosphorylations is unclear at present. Here,
      the protein kinase activity of the tyrosine kinase-linked PI3K, p110delta, is
      characterized and its functional impact assessed. In vitro autophosphorylation of
      p110delta completely down-regulates its lipid kinase activity. The single site of
      autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta.
      Antisera specific for phospho-Ser1039 revealed a very low level of
      phosphorylation of this residue in cell lines. However, p110delta that is
      recruited to activated receptors (such as CD28 in T cells) shows a time-dependent
      increase in Ser1039 phosphorylation and a concomitant decrease in associated
      lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of
      Ser/Thr phosphatases, also dramatically increases the level of Ser1039
      phosphorylated p110delta. LY294002 and wortmannin blocked these in vivo increases
      in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly
      p110delta itself, are involved in the in vivo phosphorylation of p110delta. In
      summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo
      similar to those identified under in vitro conditions, identifying a new level of
      control of these signalling molecules.

PMID- 10064596
TI  - Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes.
AB  - Inositol 1,4,5-trisphosphate (IP3) plays a key role in Ca2+ signalling, which
      exhibits a variety of spatio-temporal patterns that control important cell
      functions. Multiple subtypes of IP3 receptors (IP3R-1, -2 and -3) are expressed
      in a tissue- and development-specific manner and form heterotetrameric channels
      through which stored Ca2+ is released, but the physiological significance of the
      differential expression of IP3R subtypes is not known. We have studied the Ca2+
      signalling mechanism in genetically engineered B cells that express either a
      single or a combination of IP3R subtypes, and show that Ca2+-signalling patterns
      depend on the IP3R subtypes, which differ significantly in their response to
      agonists, i.e. IP3, Ca2+ and ATP. IP3R-2 is the most sensitive to IP3 and is
      required for the long lasting, regular Ca2+ oscillations that occur upon
      activation of B-cell receptors. IP3R-1 is highly sensitive to ATP and mediates
      less regular Ca2+ oscillations. IP3R-3 is the least sensitive to IP3 and Ca2+,
      and tends to generate monophasic Ca2+ transients. Furthermore, we show for the
      first time functional interactions between coexpressed subtypes. Our results
      demonstrate that differential expression of IP3R subtypes helps to encode IP3
      mediated Ca2+ signalling.

PMID- 10064597
TI  - The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through
      binding in the activation loop.
AB  - The Janus family of protein tyrosine kinases (JAKs) regulate cellular processes
      involved in cell growth, differentiation and transformation through their
      association with cytokine receptors. However, compared with other kinases, little
      is known about cellular regulators of the JAKs. We have recently identified a JAK
      binding protein (JAB) that inhibits JAK signaling in cells. In the studies
      presented here we demonstrate that JAB specifically binds to the tyrosine residue
      (Y1007) in the activation loop of JAK2, whose phosphorylation is required for
      activation of kinase activity. Binding to the phosphorylated activation loop
      requires the JAB SH2 domain and an additional N-terminal 12 amino acids (extended
      SH2 subdomain) containing two residues (Ile68 and Leu75) that are conserved in
      JAB-related proteins. An additional N-terminal 12-amino-acid region (kinase
      inhibitory region) of JAB also contributes to high-affinity binding to the JAK2
      tyrosine kinase domain and is required for inhibition of JAK2 signaling and
      kinase activity. Our studies define a novel type of regulation of tyrosine
      kinases and might provide a basis for the design of specific tyrosine kinase
      inhibitors.

PMID- 10064598
TI  - Regulation of JNK signaling by GSTp.
AB  - Studies of low basal Jun N-terminal kinase (JNK) activity in non-stressed cells
      led us to identify a JNK inhibitor that was purified and identified as
      glutathione S-transferase Pi (GSTp) and was characterized as a JNK-associated
      protein. UV irradiation or H2O2 treatment caused GSTp oligomerization and
      dissociation of the GSTp-JNK complex, indicating that it is the monomeric form of
      GSTp that elicits JNK inhibition. Addition of purified GSTp to the Jun-JNK
      complex caused a dose-dependent inhibition of JNK activity. Conversely,
      immunodepleting GSTp from protein extracts attenuated JNK inhibition.
      Furthermore, JNK activity was increased in the presence of specific GSTp
      inhibitors and a GSTp-derived peptide. Forced expression of GSTp decreased MKK4
      and JNK phosphorylation which coincided with decreased JNK activity, increased c
      Jun ubiquitination and decreased c-Jun-mediated transcription. Co-transfection of
      MEKK1 and GSTp restored MKK4 phosphorylation but did not affect GSTp inhibition
      of JNK activity, suggesting that the effect of GSTp on JNK is independent of the
      MEKK1-MKK4 module. Mouse embryo fibroblasts from GSTp-null mice exhibited a high
      basal level of JNK activity that could be reduced by forced expression of GSTp
      cDNA. In demonstrating the relationships between GSTp expression and its
      association with JNK, our findings provide new insight into the regulation of
      stress kinases.

PMID- 10064599
TI  - c-Jun functions as a calcium-regulated transcriptional activator in the absence
      of JNK/SAPK1 activation.
AB  - Calcium is the principal second messenger in the control of gene expression by
      electrical activity in neurons. Recruitment of the coactivator CREB-binding
      protein, CBP, by the prototypical calcium-responsive transcription factor, CREB
      and stimulation of CBP activity by nuclear calcium signals is one mechanism
      through which calcium influx into excitable cells activates gene expression. Here
      we show that another CBP-interacting transcription factor, c-Jun, can mediate
      transcriptional activation upon activation of L-type voltage-gated calcium
      channels. Calcium-activated transcription mediated by c-Jun functions in the
      absence of stimulation of the c-Jun N-terminal protein kinase (JNK/SAPK1)
      signalling pathway and does not require c-Jun amino acid residues Ser63 and
      Ser73, the two major phosphorylation sites that regulate c-Jun activity in
      response to stress signals. Similar to CREB-mediated transcription, activation of
      c-Jun-mediated transcription by calcium signals requires calcium/ calmodulin
      dependent protein kinases and is dependent on CBP function. These results
      identify c-Jun as a calcium-regulated transcriptional activator and suggest that
      control of coactivator function (i.e. recruitment of CBP and stimulation of CBP
      activity) is a general mechanism for gene regulation by calcium signals.

PMID- 10064600
TI  - TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase
      dependent, Smad4-independent pathway.
AB  - Transforming growth factor-beta (TGF-beta) exerts its effects on cell
      proliferation, differentiation and migration in part through its modulation of
      extracellular matrix components, such as fibronectin and plasminogen activator
      inhibitor-1 (PAI-1). Although the SMAD family of proteins recently has been shown
      to be a key participant in TGF-beta signaling, other signaling pathways have also
      been shown to be activated by TGF-beta. We report here that c-Jun N-terminal
      kinase (JNK), a member of the MAP kinase family, is activated in response to TGF
      beta in the human fibrosarcoma HT1080-derived cell line BAHgpt. Stable expression
      of dominant-negative forms of JNK1 and MKK4, an upstream activator of JNK,
      results in loss of TGF-beta-stimulated fibronectin mRNA and protein induction,
      while having little effect on TGF-beta-induced levels of PAI-1. The human
      fibronectin promoter contains three CRE elements, one of which has been shown to
      bind a c-Jun-ATF-2 heterodimer. Utilizing a GAL4 fusion trans-reporting system,
      we demonstrate a decrease in transactivating potential of GAL4-c-Jun and GAL4-ATF
      2 in dominant-negative JNK1- and MKK4-expressing cells. Finally, we show that TGF
      beta-induced fibronectin synthesis is independent of Smad4. These results
      demonstrate that TGF-beta-mediated fibronectin induction requires activation of
      JNK which in turn modulates the activity of c-Jun and ATF-2 in a Smad4independent
      manner.

PMID- 10064601
TI  - Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair
      the transcription function of TFIIH.
AB  - As part of TFIIH, XPB and XPD helicases have been shown to play a role in
      nucleotide excision repair (NER). Mutations in these subunits are associated with
      three genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and
      trichothiodystrophy (TTD). The strong heterogeneous clinical features observed in
      these patients cannot be explained by defects in NER alone. We decided to look at
      the transcriptional activity of TFIIH from cell lines of XP individuals. We set
      up an immunopurification procedure to isolate purified TFIIH from patient cell
      extracts. We demonstrated that mutations in two XP-B/CS patients decrease the
      transcriptional activity of the corresponding TFIIH by preventing promoter
      opening. The defect of XPB in transcription can be circumvented by artificial
      opening of the promoter. Western blot analysis and enzymatic assays indicate that
      XPD mutations affect the stoichiometric composition of TFIIH due to a weakness in
      the interaction between XPD-CAK complex and the core TFIIH, resulting in a
      partial reduction of transcription activity. This work, in addition to clarifying
      the role of the various TFIIH subunits, supports the current hypothesis that XP
      B/D patients are more likely to suffer from transcription repair syndromes rather
      than DNA repair disorders alone.

PMID- 10064602
TI  - Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in
      cytokine-dependent growth of hematopoietic cells.
AB  - STAT5 is a member of a family of transcription factors that participate in the
      signal transduction pathways of many hormones and cytokines. Although STAT5 is
      suggested to play a crucial role in the biological effects of cytokines, its
      downstream target(s) associated with cell growth control is largely unknown. In a
      human interleukin-3 (IL-3)-dependent cell line F-36P-mpl, the induced expression
      of dominant-negative (dn)-STAT5 and of dn-ras led to inhibition of IL-3-dependent
      cell growth, accompanying the reduced expression of cyclin D1 mRNA. Also, both
      constitutively active forms of STAT5A (1*6-STAT5A) and ras (H-rasG12V) enabled F
      36P-mpl cells to proliferate without added growth factors. In NIH 3T3 cells, 1*6
      STAT5A and H-rasG12V individually and cooperatively transactivated the cyclin D1
      promoter in luciferase assays. Both dn-STAT5 and dn-ras suppressed IL-3-induced
      cyclin D1 promoter activities in F-36P-mpl cells. Using a series of mutant cyclin
      D1 promoters, 1*6-STAT5A was found to transactivate the cyclin D1 promoter
      through the potential STAT-binding sequence at -481 bp. In electrophoretic
      mobility shift assays, STAT5 bound to the element in response to IL-3.
      Furthermore, the inhibitory effect of dn-STAT5 on IL-3-dependent growth was
      restored by expression of cyclin D1. Thus STAT5, in addition to ras signaling,
      appears to mediate transcriptional regulation of cyclin D1, thereby contributing
      to cytokine-dependent growth of hematopoietic cells.

PMID- 10064603
TI  - Stimulation of Tat-associated kinase-independent transcriptional elongation from
      the human immunodeficiency virus type-1 long terminal repeat by a cellular
      enhancer.
AB  - The human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR)
      initiates transcription efficiently but produces only short transcripts in the
      absence of the trans-activator protein, Tat. To determine whether a cellular
      enhancer could provide the signals required to recruit an elongation-competent
      polymerase to the HIV-1 LTR, the B cell-specific immunoglobulin heavy chain gene
      enhancer (IgHE) was inserted upstream of the LTR. The enhancer increased
      transcription in the absence of Tat between 6- and 7-fold in transfected B cells,
      but the full-length transcripts remained at basal levels in HeLa cells, where the
      enhancer is inactive. RNase-protection studies showed that initiation levels in
      the presence and absence of the enhancer were constant, but the enhancer
      significantly increased the elongation capacity of the polymerases. Tat
      stimulated elongation is strongly inhibited by the nucleoside analogue 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), which inhibits the Tat
      associated kinase, TAK (CDK9). However, polymerases initiating transcription from
      LTRs carrying the enhancer were able to efficiently elongate in the presence of
      DRB. Specific repression of TAK by expression in trans of the CDK9 kinase also
      inhibited Tat-stimulated elongation but did not inhibit enhancer-dependent
      transcription significantly. Thus, the activation of polymerase processivity by
      the IgHE involves a unique mechanism which is independent of TAK.

PMID- 10064604
TI  - Tight correlation between inhibition of DNA repair in vitro and transcription
      factor IIIA binding in a 5S ribosomal RNA gene.
AB  - UV-induced photoproducts (cyclobutane pyrimidine dimers, CPDs) in DNA are removed
      by nucleotide excision repair (NER), and the presence of transcription factors on
      DNA can restrict the accessibility of NER enzymes. We have investigatigated the
      modulation of NER in a gene promoter using the Xenopus transcription factor IIIA
      (TFIIIA)-5S rDNA complex and Xenopus oocyte nuclear extracts. TFIIIA alters CPD
      formation primarily in the transcribed strand of the 50 bp internal control
      region (ICR) of 5S rDNA. During NER in vitro, CPD removal is reduced at most
      sites in both strands of the ICR when TFIIIA is bound. Efficient repair occurs
      just outside the TFIIIA-binding site (within 10 bp), and in the absence of 5S
      rRNA transcription. Interestingly, three CPD sites within the ICR [+56, +75
      (transcribed strand) and +73 (non-transcribed strand)] are repaired rapidly when
      TFIIIA is bound, while CPDs within approximately 5 bases of these sites are
      repaired much more slowly. CPDs at these three sites may partially displace
      TFIIIA, thereby enabling rapid repair. However, TFIIIA is not completely
      displaced during NER, at least at sites outside the ICR, even though the NER
      complex could be sterically hindered by TFIIIA. Such inefficient repair of
      transcription factor binding sites could increase mutation frequency in
      regulatory regions of genes.

PMID- 10064605
TI  - Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by
      DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes.
AB  - Replication protein A (RPA) is a DNA single-strand binding protein essential for
      DNA replication, recombination and repair. In human cells treated with the
      topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2,
      the middle-sized subunit of RPA, becomes rapidly phosphorylated. This response
      appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent
      of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation
      in response to camptothecin required ongoing DNA replication. Camptothecin itself
      partially inhibited DNA synthesis, and this inhibition followed the same kinetics
      as DNA-PK activation and RPA2 phosphorylation. DNA-PK activation and RPA2
      phosphorylation were prevented by the cell-cycle checkpoint abrogator 7
      hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin
      cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which
      was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs
      interacted directly with RPA1 in vitro. We propose that the encounter of a
      replication fork with a topoisomerase-DNA cleavage complex could lead to a
      juxtaposition of replication fork-associated RPA and DNA double-strand end
      associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence
      of DNA damage to an S-phase checkpoint mechanism. KEYWORDS: camptothecin/DNA
      damage/DNA-dependent protein kinase/RPA2 phosphorylation

PMID- 10064606
TI  - Mutants of Tn3 resolvase which do not require accessory binding sites for
      recombination activity.
AB  - Tn3 resolvase promotes site-specific recombination between two res sites, each of
      which has three resolvase dimer-binding sites. Catalysis of DNA-strand cleavage
      and rejoining occurs at binding site I, but binding sites II and III are required
      for recombination. We used an in vivo screen to detect resolvase mutants that
      were active on res sites with binding sites II and III deleted (that is, only
      site I remaining). Mutations of amino acids Asp102 (D102) or Met103 (M103) were
      sufficient to permit catalysis of recombination between site I and a full res,
      but not between two copies of site I. A double mutant resolvase, with a D102Y
      mutation and an additional activating mutation at Glu124 (E124Q), recombined
      substrates containing only two copies of site I, in vivo and in vitro. In these
      novel site Ixsite I reactions, product topology is no longer restricted to the
      normal simple catenane, indicating synapsis by random collision. Furthermore, the
      mutants have lost the normal specificity for directly repeated sites and
      supercoiled substrates; that is, they promote recombination between pairs of res
      sites in linear molecules, or in inverted repeat in a supercoiled molecule, or in
      separate molecules.

PMID- 10064607
TI  - P1 ParA interacts with the P1 partition complex at parS and an ATP-ADP switch
      controls ParA activities.
AB  - The partition system of P1 plasmids is composed of two proteins, ParA and ParB,
      and a cis-acting site parS. parS is wrapped around ParB and Escherichia coli IHF
      protein in a higher order nucleoprotein complex called the partition complex.
      ParA is an ATPase that autoregulates the expression of the par operon and has an
      essential but unknown function in the partition process. In this study we
      demonstrate a direct interaction between ParA and the P1 partition complex. The
      interaction was strictly dependent on ParB and ATP. The consequence of this
      interaction depended on the ParB concentration. At high ParB levels, ParA was
      recruited to the partition complex via a ParA-ParB interaction, but at low ParB
      levels, ParA removed or disassembled ParB from the partition complex. ADP could
      not support these interactions, but could promote the site-specific DNA binding
      activity of ParA to parOP, the operator of the par operon. Conversely, ATP could
      not support a stable interaction of ParA with parOP in this assay. Our data
      suggest that ParA-ADP is the repressor of the par operon, and ParA-ATP, by
      interacting with the partition complex, plays a direct role in partition.
      Therefore, one role of adenine nucleotide binding and hydrolysis by ParA is that
      of a molecular switch controlling entry into two separate pathways in which ParA
      plays different roles.

PMID- 10064608
TI  - RNA localization.

PMID- 10064609
TI  - RNA sorting in Drosophila oocytes and embryos.
AB  - Many RNAs involved in determination of the oocyte, specification of embryonic
      axes, and establishment of germ cells in Drosophila are localized asymmetrically
      within the developing egg or syncytial embryo. Here I review the current state of
      knowledge about the cis-acting sequences involved in RNA targeting, RNA binding
      proteins; gene activities implicated in localizing specific RNAs, and the role of
      the tubulin and actin cytoskeletons in RNA sorting within the oocyte. Targeted
      RNAs are often under complex translational control, and the translational control
      of two RNAs that localize to the posterior of the oocyte, oskar and nanos, is
      also discussed. Prospects for filling gaps in our knowledge about the mechanisms
      of localizing RNAs and the importance of RNA sorting in regulating gene
      expression are also explored.

PMID- 10064610
TI  - RNA sorting in Xenopus oocytes and embryos.
AB  - Cytoplasmic localization of mRNA molecules has emerged as a powerful mechanism
      for generating spatially restricted gene expression. This process is an important
      contributor to cell polarity in both somatic cells and oocytes, and can provide
      the basis for patterning during embryonic development. In vertebrates, this
      phenomenon is perhaps best documented in the frog, Xenopus laevis, where polarity
      along the animal-vegetal axis coincides with the localization of numerous mRNA
      molecules. Research over the last several years has made exciting progress toward
      understanding the molecular mechanisms underlying cytoplasmic mRNA localization.

PMID- 10064611
TI  - The travels of mRNAs through all cells large and small.

PMID- 10064612
TI  - RNA-cytoskeletal associations.
AB  - It has become evident over the past years that a large fraction of messenger RNAs
      is tightly associated with the cytoskeleton. Whereas microtubules are involved in
      RNA-cytoskeletal association in large cells like oocytes, neurons, or
      oligodendrocytes, microfilaments play the major role in smaller somatic cell
      types. Association of RNA with cytoskeletal filaments clearly is required for
      mRNA transport, but also appears to be crucial for efficient protein synthesis.
      Recent data now shed light on how mRNAs attach to the cytoskeleton. Messenger RNA
      seems to interact with microtubules or microfilaments in the form of large
      ribonucleoprotein particles, which in some cases also contain components of the
      protein synthesis apparatus. Recently, a number of RNA binding proteins have been
      identified in flies, amphibians, and mammals that are essential for the
      interaction of mRNA with cytoskeletal filaments or with microtubule- or actin
      associated proteins. Such proteins include heterologous ribonucleoproteins, which
      are also involved in nuclear export of RNA.

PMID- 10064613
TI  - Glucocorticoids inhibit serum depletion-induced apoptosis in T lymphocytes
      expressing Bcl-2.
AB  - Depletion of growth factors and glucocorticoids are known to induce apoptosis and
      inhibit growth in T lymphocytes. We have examined the effect of Bcl-2 expression
      on the cellular response to growth factor depletion in the presence or absence of
      glucocorticoids. Cell growth was determined by cell counting and viability was
      quantitated by dye exclusion. Apoptosis was evaluated by flow cytometry, analysis
      of DNA integrity, and enzymatic determination of caspase-3-like activity. Serum
      depletion and glucocorticoid administration inhibited cell growth and stimulated
      apoptosis in Bcl-2 negative cells. Cotreatment with both stimuli had additive
      effects on apoptosis but not on inhibition of cell growth. Bcl-2 expression
      abrogated the repressive effect of glucocorticoids on apoptosis but not on cell
      growth. In contrast, neither apoptosis nor growth inhibition induced by serum
      depletion of cells was blocked by Bcl-2 expression. However, glucocorticoid
      treatment of Bcl-2-overexpressing cells protected them from apoptosis induced by
      serum depletion. Glucocorticoid protection of Bcl-2-overexpressing cells from
      serum depletion-induced apoptosis was mimicked by other inducers of apoptosis,
      which act to inhibit protein synthesis. These data suggest that Bcl-2 expression
      can switch the effect of glucocorticoids from proapoptotic to antiapoptotic when
      lymphocytes expressing Bcl-2 are exposed to other apoptotic stimuli.

PMID- 10064614
TI  - Vitronectin is a constituent of ocular drusen and the vitronectin gene is
      expressed in human retinal pigmented epithelial cells.
AB  - Age-related macular degeneration (AMD) leads to dysfunction and degeneration of
      retinal photoreceptor cells. This disease is characterized, in part, by the
      development of extracellular deposits called drusen. The presence of drusen is
      correlated with the development of AMD, although little is known about drusen
      composition or biogenesis. Drusen form within Bruch's membrane, a stratified
      extracellular matrix situated between the retinal pigmented epithelium and
      choriocapillaris. Because of this association, we sought to determine whether
      drusen contain known extracellular matrix constituents. Antibodies directed
      against a battery of extracellular matrix molecules were screened on drusen
      containing sections from human donor eyes, including donors with clinically
      documented AMD. Antibodies directed against vitronectin, a plasma protein and
      extracellular matrix component, exhibit intense and consistent reactivity with
      drusen; antibodies to the conformationally distinct, heparin binding form of
      human vitronectin are similarly immunoreactive. No differences in vitronectin
      immunoreactivity between hard and soft drusen, or between macular and
      extramacular regions, have been observed. RT-PCR analyses revealed that
      vitronectin mRNA is expressed in the retinal pigmented epithelium (RPE)-choroidal
      complex and cultured RPE cells. These data document that vitronectin is a major
      constituent of human ocular drusen and that vitronectin mRNA is synthesized
      locally. Based on these data, we propose that vitronectin may participate in the
      pathogenesis of AMD.

PMID- 10064615
TI  - Bcl-2 alters the balance between apoptosis and necrosis, but does not prevent
      cell death induced by oxidized low density lipoproteins.
AB  - Oxidized low density lipoproteins (oxLDL) participate in atherosclerosis plaque
      formation, rupture, and subsequent thrombosis. Because oxLDL are toxic to
      cultured cells and Bcl-2 protein prevents apoptosis, the present work aimed to
      study whether Bcl-2 may counterbalance the toxicity of oxLDL. Two experimental
      model systems were used in which Bcl-2 levels were modulated: 1) lymphocytes in
      which the (high) basal level of Bcl-2 was reduced by antisense oligonucleotides;
      2) HL60 and HL60/B (transduced by Bcl-2) expressing low and high Bcl-2 levels,
      respectively. In cells expressing relatively high Bcl-2 levels (lymphocytes and
      HL60/B), oxLDL induced mainly primary necrosis. In cells expressing low Bcl-2
      levels (antisense-treated lymphocytes, HL60 and ECV-304 endothelial cells), the
      rate of oxLDL-induced apoptosis was higher than that of primary necrosis. OxLDL
      evoked a sustained calcium rise, which is a common trigger to necrosis and
      apoptosis since both types of cell death were blocked by the calcium chelator
      EGTA. Conversely, a sustained calcium influx elicited by the calcium ionophore
      A23187 induced necrosis in cells expressing high Bcl-2 levels and apoptosis in
      cells expressing low Bcl-2 levels. This suggests that Bcl-2 acts downstream from
      the calcium peak and inhibits only the apoptotic pathway, not the necrosis
      pathway, thus explaining the apparent shift from oxLDL-induced apoptosis toward
      necrosis when Bcl-2 is overexpressed.

PMID- 10064616
TI  - Psoriatic keratinocytes show reduced IRF-1 and STAT-1alpha activation in response
      to gamma-IFN.
AB  - Psoriasis is a chronic inflammatory dermatosis characterized by
      hyperproliferative keratinocytes (KC). The skin lesions are infiltrated by T
      cells, which secrete gamma interferon (gamma-IFN) and are believed to be
      necessary to maintain the psoriatic phenotype. In normal KC, gamma-IFN is a
      potent inhibitor of proliferation, but proliferation of KC persists in psoriatic
      plaques despite the presence of gamma-IFN. Immunostaining of interferon
      regulatory factor-1 (IRF-1) revealed that IRF-1 was localized to the basal cells
      of the epidermis in normal and in nonlesional psoriatic skin, but was suprabasal
      or completely absent in lesional psoriatic skin. This finding led to the
      hypothesis that abnormal signaling in the gamma-IFN pathway may occur in
      psoriatic KC. To test this hypothesis, we measured activation of IRF-1 and signal
      transducer and activator of transcription (STAT)-1alpha transcription factors in
      KC after stimulation with gamma-IFN. Primary cultures of KC from normal and
      nonlesional psoriatic skin were stimulated with gamma-IFN and subsequent
      transcription factor activation was measured by electrophoretic mobility shift
      assay. Psoriatic KC showed a reduced induction of IRF-1 and STAT-1alpha
      activation after stimulation with gamma-IFN, compared with normal KC. Reduced
      activation of IRF-1 and STAT-1alpha in response to gamma-IFN indicates a
      fundamental defect in the growth and differentiation control of psoriatic KC in
      the absence of the influence of other cell types.

PMID- 10064617
TI  - A functional, discontinuous HIV-1 gp120 C3/C4 domain-derived, branched, synthetic
      peptide that binds to CD4 and inhibits MIP-1alpha chemokine binding.
AB  - This paper describes a branched synthetic peptide [3.7] that incorporates
      sequence discontinuous residues of HIV-1 gp120 constant regions. The approach was
      to bring together residues of gp120 known to interact with human cell membranes
      such that the peptide could fold to mimic the native molecule. The peptide
      incorporates elements of both the conserved CD4 and CCR5 binding sites. The 3.7
      peptide, which cannot be produced by conventional genetic engineering methods, is
      recognized by antiserum raised to native gp120. The peptide also binds to CD4 and
      competitively inhibits binding of QS4120 an antibody directed against the CDR2
      region of CD4. When preincubated with the CD4+ve MM6 macrophage cell line, which
      expresses mRNA for the CCR3 and CCR5 chemokine receptors, both 3.7 and gp120
      inhibit binding of the chemokine MIP-1alpha. The peptide also inhibits infection
      of primary macrophages by M-tropic HIV-1. Thus, 3.7 is a prototype candidate
      peptide for a vaccine against HIV-1 and represents a novel approach to the
      rational design of peptides that can mimic complex sequence discontinuous ligand
      binding sites of clinically relevant proteins.

PMID- 10064618
TI  - Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis.
AB  - Carbonic anhydrase III (CA III; EC 4.2.1.1) is a cytoplasmic enzyme that exhibits
      a relatively low carbon dioxide hydratase activity. It is expressed at a very
      high level in skeletal muscle, where physical exercise has been shown to increase
      free radical production. In this work we show the effect of overexpression of CA
      III on cellular response to oxidative stress. Rat CA III cDNA was transfected to
      NIH/3T3 cells, which have no endogenous CA III expression. The isolated clones
      expressed CA III mRNA and protein. The protein was localized to cytoplasm and
      nuclei. Compared to parental cells, transfected cells showed lower basal oxidized
      state as judged by measurement of intracellular reactive oxygen species (ROS)
      using fluorescent dye and an image analysis system. Addition of exogenous H2O2 to
      cells induced a rapid increase of ROS in control but not in CA III overexpressing
      cells. Association of this phenomenon with CA III expression was further
      confirmed by showing that overexpression of CA II could not prevent H2O2
      stimulated increase of ROS. In proliferation assays, CA III overexpressing cells
      grew faster and were more resistant to cytotoxic concentrations of H2O2 than
      control cells. After a 16 h exposure to oxidative stress, the number of apoptotic
      cells was also reduced in transfectants. Our results suggest that CA III
      functions as an oxyradical scavenger and thus protects cells from oxidative
      damage. A lower level of free radicals in CA III overexpressing cells may also
      affect growth signaling pathways.

PMID- 10064619
TI  - Altered gene expression and functions of mitochondria in human nephrotic
      syndrome.
AB  - The molecular basis of glomerular permselectivity remains largely unknown. The
      congenital nephrotic syndrome of the Finnish type (CNF) characterized by massive
      proteinuria already present but without extrarenal symptoms is a unique human
      disease model of pure proteinuria. In search of genes and pathophysiologic
      mechanisms associated with proteinuria, we used differential display-PCR to
      identify differences in gene expression between glomeruli from CNF and control
      kidneys. A distinctly underexpressed PCR product of the CNF kidneys showed over
      98% identity with a mitochondrially encoded cytochrome c oxidase (COX I). Using a
      full-length COX I cDNA probe, we verified down-regulation of COX I mRNA to 1/4 of
      normal kidney values on Northern blots. In addition, transcripts of other
      mitochondrially encoded respiratory chain complexes showed a similar down
      regulation whereas the respective nuclearly encoded complexes were expressed at
      comparable levels. Additional studies using histochemical, immunohistochemical,
      in situ hybridization, RT-PCR, and biochemical and electron microscopic methods
      all showed a mitochondrial involvement in the diseased kidneys but not in
      extrarenal blood vessels. As a secondary sign of mitochondrial dysfunction,
      excess lipid peroxidation products were found in glomerular structures in CNF
      samples. Our data suggest that mitochondrial dysfunction occurs in the kidneys of
      patients with CNF, with subsequent lipid peroxidation at the glomerular basement
      membrane. Our additional studies have revealed similar down-regulation of
      mitochondrial functions in experimental models of proteinuria. Thus,
      mitochondrial dysfunction may be a crucial pathophysiologic factor in this
      symptom.

PMID- 10064620
TI  - Injury-induced gelatinase and thrombin-like activities in regenerating and
      nonregenerating nervous systems.
AB  - It is now widely accepted that injured nerves, like any other injured tissue,
      need assistance from their extracellular milieu in order to heal. We compared the
      postinjury activities of thrombin and gelatinases, two types of proteolytic
      activities known to be critically involved in tissue healing, in nonregenerative
      (rat optic nerve) and regenerative (fish optic nerve and rat sciatic nerve)
      neural tissue. Unlike gelatinases, whose induction pattern was comparable in all
      three nerves, thrombin-like activity differed clearly between regenerating and
      nonregenerating nervous systems. Postinjury levels of this latter activity seem
      to dictate whether it will display beneficial or detrimental effects on the
      capacity of the tissue for repair. The results of this study further highlight
      the fact that tissue repair and nerve regeneration are closely linked and that
      substances that are not unique to the nervous system, but participate in wound
      healing in general, are also crucial for regeneration or its failure in the
      nervous system.

PMID- 10064621
TI  - Activation of the adult mode of ovine growth hormone receptor gene expression by
      cortisol during late fetal development.
AB  - The developmental and tissue-specific regulation of growth hormone receptor (GHR)
      mRNA expression is complex and involves alternate leader exon usage. The
      transcript composition of hepatic GHR mRNA has therefore been determined in fetal
      sheep during late gestation and after experimental manipulation of fetal plasma
      cortisol levels by fetal adrenalectomy and exogenous cortisol infusion, using
      RNase protection assays and a riboprobe containing exons 1A, 2, and 3 of the
      ovine GHR gene. Expression of the adult liver-specific GHR mRNA transcript
      containing exon 1A was not detected earlier than 138 days of gestation (term 145
      +/-2 days). Thereafter, expression of this leader exon increased and accounted
      for 25-30% of the total GHR mRNA in the fetal liver at term. Hepatic GHR mRNA
      derived from leader exons other than 1A was detectable at 97 days and increased
      in abundance toward term in parallel with the normal prepartum rise in fetal
      plasma cortisol. Abolition of this cortisol surge by fetal adrenalectomy
      prevented both the activation of exon 1A expression and the prepartum rise in GHR
      mRNA derived from the other leader exons in fetal ovine liver. Conversely,
      raising cortisol levels by exogenous infusion earlier in gestation prematurely
      activated exon 1A expression and enhanced the abundance of GHR mRNA transcripts
      derived from the other leader exons. Cortisol therefore appears to activate the
      adult mode of GHR gene expression in fetal ovine liver during late gestation.
      These observations have important implications for the maturation of the
      somatotrophic axis and for the onset of GH-dependent growth after birth.

PMID- 10064622
TI  - Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1
      osteoblasts.
AB  - In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild
      (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto
      oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein
      kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is
      mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic
      TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA
      sensitive isoforms of PKC are not responsible for c-fos up-regulation. In
      addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2)
      levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2
      (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked
      whether the increase in c-fos mRNA was due to centrifugation-induced PGE2
      release. Pretreatment with the cyclooxygenase inhibitors indomethacin and
      flurbiprofen did not hinder the early induction of c-fos by mechanical
      stimulation. We conclude that c-fos expression induced by mild mechanical loading
      is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not
      necessarily dependent on the action of newly synthesized PGE2.

PMID- 10064623
TI  - The Ice Man's diet as reflected by the stable nitrogen and carbon isotopic
      composition of his hair.
AB  - Establishing the diets of ancient human populations is an integral component of
      most archaeological studies. Stable isotope analysis of well-preserved bone
      collagen is the most direct approach for a general assessment of paleodiet.
      However, this method has been limited by the scarcity of well-preserved skeletal
      materials for this type of destructive analysis. Hair is preserved in many
      burials, but is often overlooked as an alternative material for isotopic
      analysis. Here we report that the stable carbon and nitrogen isotope values for
      the hair of the 5200 year-old Ice Man indicates a primarily vegetarian diet, in
      agreement with his dental wear pattern. Whereas previous investigations have
      focused on bone collagen, the stable isotope composition of hair may prove to be
      a more reliable proxy for paleodiet reconstruction, particularly when skeletal
      remains are not well preserved and additional archaeological artifacts are
      unavailable.

PMID- 10064625
TI  - Experimental biology '99 april 17-21, 1999 washington, D.C 

PMID- 10064624
TI  - Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha
      production and accelerated IL-10 expression.
AB  - Cytokines play a pivotal role in the pathogenesis of septic shock.
      Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas
      the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino
      acid glycine (GLY) has been shown to protect against endotoxin shock in the rat
      by inhibiting TNF-alpha production. In the current study we investigated the role
      of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression,
      phagocytosis, and cytokine production on purified monocytes from healthy donors.
      GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas
      CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased
      significantly. GLY decreased LPS-induced TNF-alpha production (P<0.01) and
      increased IL-10 expression of purified monocytes. Similarly, in a whole blood
      assay, GLY reduced TNF-alpha (P<0.0001) and IL-1beta (P<0.0001) synthesis and
      increased IL-10 expression (P<0.05) in a dose-dependent manner. The inhibitory
      effects of GLY were neutralized by strychnine, and the production of IL-10 and
      TNF-alpha was augmented by anti-IL-10 antibodies. Furthermore, GLY decreased the
      amount of IL-1beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a
      potential to be used as an additional immunomodulatory tool in the early phase of
      sepsis and in different pathophysiological situations related to hypoxia and
      reperfusion.

PMID- 10064627
TI  - Biodiversity: our greatest natural resource.

PMID- 10064628
TI  - Q-switched neodymium:yttrium-aluminum-garnet laser treatment of lentigo maligna.
AB  - Lentigo maligna is a premalignant lesion of atypical melanocytes that typically
      arises on the head and neck of elderly patients. It is considered a melanoma in
      situ with a significant risk for transformation to invasive lentigo maligna
      melanoma. Surgery is the preferred method of treatment; however, because of the
      advanced age of the typical patient with lentigo maligna, the frequency of
      complicating medical problems, and the cosmetic or functional aspects of
      treatment, surgical excision is not always feasible. The purpose of this pilot
      study was to evaluate the efficacy and safety of Q-switched neodymium:yttrium
      aluminum-garnet laser treatment of lentigo maligna. Eight patients were treated
      with 532 and/or 1064 nm wavelengths from the laser. All patients showed a
      response to laser therapy, and 2 patients treated with 1 treatment from each
      wavelength had complete eradication of the LM, with no evidence of recurrence in
      42 months. Further study is warranted, but Q-switched neodymium:yttrium-aluminum
      garnet laser is a promising alternative treatment for lentigo maligna.

PMID- 10064629
TI  - Long-term follow-up of submandibular duct rerouting for the treatment of
      sialorrhea in the pediatric population.
AB  - OBJECTIVE: To determine the long-term control of sialorrhea in children who
      underwent submandibular duct rerouting (SMDR) and to identify potential
      preoperative predictors of outcome. DESIGN: Retrospective chart review of
      children who underwent SMDR; information updated by discussion with the permanent
      caregiver. SETTING: Tertiary care center. PATIENTS: Children who had significant
      sialorrhea resulting from a variety of neuromuscular disabilities between January
      1980 and December 1995. OUTCOME: We report the outcome on 59 patients who
      underwent SMDR for the treatment of sialorrhea. Patients were ascribed a
      preoperative sialorrhea and global neurologic deficit score. Postoperative
      outcome was scored as marked, moderate, no improvement, or worse. Twenty-eight of
      59 (47.4%), 28 of 59 (47.4%), and 3 of 59 (5.1%) of the patients had preoperative
      sialorrhea scores of 3 (profuse), 2 (moderate), and 1 (mild), respectively.
      Twenty of 59 (33.9%), 29 of 59 (49.2%), and 10 of 59 (16.9%) had preoperative
      scores of 3 (severe), 2 (moderate), and 1 (mild) neurologic impairment,
      respectively. Mean time to follow-up of the 59 patients was 5.46 years.
      Postoperative improvement scores were as follows: 50.8% had marked, 28.8% had
      moderate, and 20% had no to minimal improvement in their sialorrhea. Two patients
      were transiently worse. A complication rate of 11.3% (9 of 79) was demonstrated:
      7 ranulae, 1 transient swelling of the floor of the mouth, and 1 submandibular
      gland infection. The preoperative global neurologic deficit score was found to be
      more predictive of surgical outcome than sialorrhea score.

PMID- 10064630
TI  - Use of the superior meatus and superior turbinate in the endoscopic approach to
      the sphenoid sinus.
AB  - Endoscopic surgery of the posterior ethmoid and sphenoid sinuses can present the
      operator with a considerable challenge. Although endoscopic training and
      physician experience have increased significantly in the past decade, surgical
      complications such as optic nerve trauma and cerebrospinal fluid leak still
      occur. Surgeons reporting such complications cite a lack of orientation within
      the dissection field as a primary cause. Because endoscopic sinus surgery is now
      being performed more routinely, surgical strategies designed to reduce the risk
      of complications are more important than ever. An anatomic landmark that could
      reliably orient the dissection within the posterior ethmoids and guide the
      surgeon to the sphenoid sinus could reduce the possibility of such adverse
      outcomes. In our experience identification of the superior meatus and superior
      turbinate provides a reliable landmark within the dissection field that can
      ensure surgical orientation to the operator. This technique allows safe, reliable
      dissection of the posterior ethmoids and an efficient approach to the sphenoid
      sinus, especially in patients undergoing revision surgery. In this article our
      technique for the identification and definition of the superior meatus and
      superior turbinate is presented, and the advantages of using this landmark in
      sinus surgery are discussed. In our experience identification of the superior
      meatus, superior turbinate, posterior skull base, and medial orbital wall defines
      a parallelogram-shaped box, which delineates the sphenoid face. This box provides
      the necessary orientation to guide the surgeon's entrance into the sphenoid sinus
      through the posterior ethmoid sinus (as Messerklinger described). Techniques for
      identifying the superior turbinate and meatus and for entering the sphenoid are
      detailed.

PMID- 10064631
TI  - Botulinum toxin injection to improve tracheoesophageal speech after total
      laryngectomy.
AB  - Total laryngectomy patients, after undergoing a tracheoesophageal puncture (TEP),
      may have poor TEP speech because of hypertonicity or spasm of the
      pharyngoesophageal segment (PES). Conventional treatment options include speech
      therapy, PES dilation, pharyngeal neurectomy, and myotomy. Botulinum toxin
      injection into the PES has recently been reported to be effective for this
      disorder. However, data accumulated were based primarily on subjective analyses.
      This prospective investigation used both qualitative and quantitative measures to
      assess the effects of videofluoroscopy-guided botulinum toxin injection on TEP
      voice quality in laryngectomees with PES dysfunction. Patients underwent voice
      analyses, tracheal air pressure measures, and barium swallows before and after
      botulinum toxin injection. Seven of 8 patients had significant voice quality
      improvement, and tracheal air pressures normalized in 6 of 8 patients after
      injection. Videofluoroscopic botulinum toxin injection into the PES is
      efficacious, safe, and cost-effective and should be considered as a first-line
      therapy for the treatment of laryngectomees with poor quality TEP speech caused
      by PES dysfunction.

PMID- 10064632
TI  - Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for
      the treatment of acute sinusitis in adults.
AB  - In this comparative trial, outpatients with acute sinusitis were randomly
      assigned to receive levofloxacin (500 mg orally once daily) or amoxicillin
      clavulanate (500/125 mg orally 3 times daily) for 10 to 14 days. The success
      rates (cured and improved) 2 to 5 days after the end of treatment were 88.4% for
      the 267 clinically evaluable patients who received levofloxacin and 87.3% for the
      268 clinically evaluable patients who received amoxicillin-clavulanate. Drug
      related adverse events occurred in a smaller percentage of patients in the
      levofloxacin treatment group (7.4%) than in the amoxicillin-clavulanate treatment
      group (21.2%). The most common of these were nausea, diarrhea, vaginitis, and
      abdominal pain for levofloxacin-treated patients and diarrhea, vaginitis, nausea,
      genital moniliasis, abdominal pain, vomiting, and flatulence for amoxicillin
      clavulanate-treated patients. The results of this study show that once-daily
      administration of levofloxacin is as effective and better tolerated than
      amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis
      in adult outpatients.

PMID- 10064633
TI  - Clinical practice guidelines for the management of chronic sinusitis in children.
AB  - Chronic sinusitis in children is a common and vexing disease for clinicians and
      the public. There are insufficient data in the literature to develop an evidence
      based clinical guideline. Experience in managing pediatric chronic sinusitis has
      been gained through a multidisciplinary clinic at our institution during the past
      3 years. A panel of experts was formed, and with the guidance of a guideline
      methodologist, the development of a rigorous outcome-based guideline was
      undertaken. Symptom-improvement and recurrence estimates for a variety of medical
      and surgical treatments were assessed. Wide probability estimates were made by
      the panelists in most cases. Although we refrained from making specific
      recommendations, we developed a ranked series of practical treatment options
      taking into account side effects and costs.

PMID- 10064634
TI  - Postoperative hemorrhage after tonsillectomy: use of ketorolac tromethamine.
AB  - Recent reports have associated an increased incidence of bleeding after
      tonsillectomy with the perioperative use of ketorolac tromethamine. To review
      this association, we examined the hospital and office records of 310 pediatric
      patients who underwent tonsillectomy with or without adenoidectomy at our
      institution during a 2-year period. Of these patients, 213 received ketorolac
      administered as a single dose at the conclusion of the procedure. The remaining
      97 patients did not receive ketorolac. The frequency of postoperative hemorrhage
      was not found to differ significantly between these 2 groups (2.3% vs. 3.1%
      respectively, P = 0.71). Furthermore, the average time to discharge after surgery
      was significantly shorter in those patients who received ketorolac than in those
      who did not (8.5 hours vs. 12.5 hours, respectively, P < 0.0001). The frequency
      of overnight hospital stays was also significantly lower in those patients who
      received ketorolac (16.0% vs. 31.6%, respectively, P < 0.01). Concern over the
      potential for increased hemorrhage after tonsillectomy has led several authors to
      caution against the use of ketorolac in this setting. In our study, however, the
      use of ketorolac was not found to increase the incidence of posttonsillectomy
      hemorrhage and furthermore was associated with a significant decrease in the
      length of hospital stay as well as a decreased likelihood of overnight hospital
      stay after surgery.

PMID- 10064635
TI  - Is parental perception an accurate predictor of childhood hearing loss? A
      prospective study.
AB  - OBJECTIVE: We performed this study to assess whether parental perception of
      hearing loss predicted the results of audiometric testing in children with
      recurrent otitis media or persistent otitis media with effusion. METHODS: As part
      of a larger prospective observational outcomes study of children undergoing
      tympanostomy tube placement, the child's parent completed a standardized
      questionnaire before and after tube placement. In addition, patients underwent
      age-appropriate audiologic threshold and tympanometry testing before and after
      tube placement. RESULTS: We enrolled 113 patients (median age, 2 years), and 93
      (82%) completed follow-up. Before treatment, parental perception of hearing loss
      did not predict hearing threshold level. After tube placement, parental
      perception of hearing loss was also poorly correlated with change in threshold.
      CONCLUSIONS: Parental perception of their child's hearing loss is a poor
      predictor of objective audiologic findings both before and after treatment with
      tympanostomy tubes. These findings have important implications concerning the
      importance of screening for hearing loss in children with otitis media with
      effusion.

PMID- 10064636
TI  - Hydroxyapatite canal wall reconstruction/mastoid obliteration.
AB  - The controversy regarding removal of the posterior external canal wall during
      mastoid surgery spans many decades. There are inherent advantages and
      disadvantages to either removing or not removing the canal wall. The operation
      must be tailored to the patient and his or her unique situation. We describe our
      experience with external canal wall reconstruction and mastoid obliteration with
      hydroxyapatite in an effort to derive the best of both philosophies.
      Hydroxyapatite has been used in 3 different forms including granules, a preformed
      canal wall prosthesis, and with a block of hydroxyapatite sculpted to fit the
      individual defect. A total of 36 patients with up to 54-month follow-up are
      reported. Details of the techniques used, with advantages and pitfalls, are
      described.

PMID- 10064637
TI  - Computed tomography and the diagnosis of coalescent mastoiditis.
AB  - OBJECTIVE: To evaluate the sensitivity and accuracy of temporal bone CT findings
      for the diagnosis of acute coalescent mastoiditis. DESIGN: CT scans were blindly
      scored for mastoid bone integrity (air cell septae, sigmoid cortical plate, and
      lateral cortical wall) by an otologist and 2 neuroradiologists. Scores were
      analyzed to determine their sensitivity and specificity for acute coalescent
      mastoiditis. SUBJECTS: Twenty-one patients with acute coalescent mastoiditis or
      acute noncoalescent mastoiditis and 12 patients with chronic mastoiditis.
      SETTING: Academic tertiary care facility. RESULTS: Pair-wise interobserver
      agreement was good to excellent (kappa = 0.4 to 0.83) for the sigmoid plate, the
      lateral cortex, and the septae. Scores for the sigmoid plate were significantly
      greater (indicative of greater bone destruction) in the coalescent group than in
      either the noncoalescent group or the chronic group (P < 0.05). Within the
      coalescent group, scores were highest for the sigmoid plate, followed by the
      septae and the lateral wall. Sensitivity and specificity for coalescent
      mastoiditis were both highest for the sigmoid plate (67% and 90%, respectively).
      CONCLUSIONS: Erosion of the cortical plate overlying the sigmoid sinus is the
      most sensitive and specific CT finding for distinguishing coalescent from
      noncoalescent acute mastoiditis.

PMID- 10064638
TI  - Trigeminal schwannomas: the role of the neurotologist in multidisciplinary
      management.
AB  - Trigeminal neuromas are slow-growing benign tumors representing approximately 10%
      of all intracranial neuromas and less than 0.5% of all intracranial tumors.
      Historically, excision of these tumors through traditional neurosurgical routes-
      including the frontotemporal transsylvian, subtemporal-intradural, subtemporal
      transtentorial, or suboccipital approaches--has resulted in an unsatisfactorily
      high rate of recurrence. In this study we compare contemporary skull
      base/neurotologic approaches with conventional procedures for trigeminal neuroma
      extirpation.

PMID- 10064639
TI  - Surgical modification of the difficult mastoid cavity.
AB  - This retrospective study used a computerized otologic database to identify
      patients undergoing revision surgery for a draining cavity unresponsive to
      medical therapy, with at least a 2-year follow-up. The surgical intervention
      involved partial mastoid obliteration and restoration of the middle ear space by
      use of cartilage reconstruction of the tympanic membrane. Ossicular
      reconstruction was achieved with either a partial or total ossicular replacement
      prosthesis. Because this technique involved contouring the mastoid cavity, the
      problems that usually occur, such as drainage or debris collection, were
      alleviated. In addition, re-establishment of the middle ear space often restored
      hearing. A completely dry cavity was achieved in 18 of 20 patients. An overall
      statistically significant improvement in hearing (P < 0.05) was obtained, with
      the mean pure-tone average air-bone gap decreasing to 16.1 dB from 36.5 dB. This
      technique has proven to be a useful adjunct in the surgical management of the
      chronically draining cavity.

PMID- 10064640
TI  - Factors related to dropout in a study of head and neck cancer patients after
      surgery.
AB  - The extent and nature of dropout was assessed in a longitudinal study whose
      objective was to define and quantify the functional effects of oral surgical
      resection and reconstruction on speech and swallowing function in patients with
      head and neck cancer. Of 150 patients who were enrolled to be followed up with
      speech and swallow assessments for 1 year after surgery, 113 (75%) dropped out
      and 37 (25%) returned to complete the study at the final 12-month evaluation
      point. In general, those completing the study had a smaller resection than the
      patients who dropped out before the 12-month evaluation. Fifty percent of the
      dropout was accounted for by medical reasons, 23% by administrative reasons, and
      27% by patient-specific reasons (i.e., reasons known only to the patient).
      Analysis of the dropout categories revealed that higher cancer stage, larger
      volume of resection, and having a flap surgical closure versus a primary closure
      or skin graft increased a patient's chance of dropping out. A larger volume of
      resection was also related to an increased chance of being a patient-specific
      dropout. Patients who reported no or low alcohol usage had a greater chance of
      completing follow-up than being a patient-specific dropout.

PMID- 10064641
TI  - Squamous cell carcinoma of the buccal mucosa.
AB  - The purpose of this study was to establish treatment criteria for patients with
      early-stage squamous cell carcinoma of the buccal mucosa. Thirty-one patients
      were analyzed in a retrospective fashion. Distribution of patients according to
      tumor stage was relatively even. Within 5 years recurrent disease developed in
      nearly 80% of evaluable patients. There was a 100% overall incidence of local
      disease recurrence for patients with stage I and II tumors treated with wide
      local excision alone and followed up for more than 2 years. On the basis of these
      data, we conclude that wide local excision for early-stage buccal carcinoma is
      associated with a high local failure rate. Possible causes for failure and
      alternative treatment approaches are discussed.

PMID- 10064642
TI  - Symptoms as an index of biologic behavior in head and neck cancer.
AB  - The TNM staging system for head and neck cancer is based on the morphologic
      description of the tumor and disregards the clinical condition of the patient.
      Cancer symptoms were evaluated as a biologic index of disease to improve survival
      estimates. The medical records of 1010 patients receiving initial cancer
      treatment between 1980 and 1991 were retrospectively reviewed. The mean survival
      duration was 62 months for the entire population. By use of SAS statistical
      software (SAS Institute, Cary, NC), 48 symptom variables were screened by
      univariate analysis, and 23 of these variables were selected for entry into a Cox
      proportional hazards model on the basis of survival duration. Dysphagia, otalgia,
      neck lump, and weight loss were identified as independent predictors of survival
      duration (P < 0.01). A composite symptom-severity staging system was created on
      the basis of the 4 symptoms. Mean survival duration (95% CI) by symptom-severity
      stage was as follows: none, 74 months (70 to 79 months); mild, 56 months (51 to
      61 months); moderate, 40 months (33 to 47 months); and severe, 31 months (22 to
      41 months) (chi 2 = 30.8, P = 0.0001). Survival duration by TNM stage was as
      follows: I, 89 months (82 to 95 months); II, 71 months (65 to 78 months); III, 53
      months (47 to 59 months); and IV, 42 months (37 to 47 months) (chi 2 = 56.2, P =
      0.0001). When symptom-severity stage was entered in a proportional-hazards model
      along with TNM stage, comorbidity, age, and alcohol use, all 5 variables were
      independently predictive of survival duration (risk ratio: symptom severity 1.28,
      TNM 1.33, comorbidity 1.80, age 1.47, alcohol use 1.09). Appropriately defined
      symptom variables contain important prognostic information, which is independent
      of the TNM system. Therefore symptoms provide an index of biologic behavior in
      head and neck cancer.

PMID- 10064643
TI  - Subcranial approach to tumors of the anterior cranial base: analysis of current
      and traditional surgical techniques.
AB  - Tumors of the anterior cranial base have previously required a craniofacial
      resection to allow adequate tumor extirpation. An analysis of current and
      traditional techniques demonstrates a significant reduction in operative time,
      complication rate, and intensive care unit and total hospital length of stay with
      the use of the subcranial approach as compared with the traditional frontal
      craniotomy and lateral rhinotomy approach. The subcranial approach is both cost
      and time efficient and provides comparable morbidity and mortality rates.

PMID- 10064644
TI  - Recurrent cutaneous melanoma of the head and neck.
AB  - INTRODUCTION: Recurrent cutaneous melanoma is generally regarded as having an
      extremely poor prognosis, particularly when regional lymph nodes are involved. A
      few reports have documented long-term survival among those patients treated for
      regionally recurrent melanoma. METHODS: This article reviews patients at our
      institution undergoing complete neck dissection for recurrent head and neck
      melanoma. RESULTS: Twenty-six patients with locoregionally recurrent cutaneous
      melanoma of the head and neck underwent complete neck dissection with or without
      parotidectomy. Seventeen of these procedures were for clinically evident cervical
      lymphadenopathy, whereas 9 of the neck dissections were done electively. Fourteen
      of the 17 patients with clinical adenopathy were confirmed to have cervical lymph
      node metastases. Two of the 9 patients who underwent elective neck dissections
      had pathologic lymph nodes. At 5 years, 38% of the patients with isolated neck
      recurrences not also having concurrent primary site recurrence were alive without
      disease. CONCLUSIONS: These results provide further evidence suggesting a benefit
      in the form of long-term survival or cure for patients receiving aggressive
      surgical treatment for resectable recurrent head and neck melanoma involving
      cervical lymphatics in the absence of distant metastases.

PMID- 10064645
TI  - Labyrinthine fenestration in the guinea pig.
AB  - OBJECTIVE: To evaluate the auditory effects of single, double, and triple
      semicircular canal fenestration procedures, with and without sealing the
      labyrinthine defect. BACKGROUND: Violation of the inner ear remains a feared
      complication in otologic surgery because it commonly leads to profound
      sensorineural hearing loss. It has been assumed that the natural history of
      labyrinthine injury in the guinea pig is similar to that in human beings;
      however, this assumption has not been rigorously studied. DESIGN: Prospective,
      randomized, and controlled animal study. SUBJECTS: Sixty pigmented guinea pigs.
      OUTCOME: Click-evoked electrocochleographic response, with same-ear
      prefenestration control. RESULTS: All of the fenestration groups had elevated
      auditory thresholds at 1 hour when compared with controls (P < 0.01); however,
      this difference lost statistical significance at 1 and 4 weeks. The degree of
      labyrinthine injury did not correlate with the degree of hearing loss or with the
      incidence of anacusis. Hearing remained stable during the study period. Sealing
      the fenestration had no significant audiologic effect (P > 0.40). CONCLUSIONS:
      The guinea pig model of labyrinthine fenestration may not be representative of
      the human condition.

PMID- 10064646
TI  - Betahistine increases vestibular blood flow.
AB  - Betahistine is used for treatment of several vestibular disorders. Despite the
      accepted use of this histamine-like substance, its mechanism of action is not
      well understood. The purpose of this study was to assess the possibility that one
      of the activities of betahistine is increasing blood flow in the peripheral
      vestibular end organs. Using a novel surgical approach, we identified the
      posterior semicircular canal ampulla of guinea pigs and placed a laser Doppler
      probe in position to obtain blood flow measurements from the posterior
      semicircular canal ampulla. Blood pressure, heart rate, and vestibular blood flow
      were continuously recorded. Concentration-response curves were obtained for
      betahistine (2.5, 5, 7.5, and 10 mg/kg) and control-vehicle (0.15 mol/L NaCl)
      infusions. A separate group of subjects was pretreated with the competitive
      selective H3 agonist, thioperimide maleate, before betahistine treatment.
      Increases in vestibular blood flow and decreases in blood pressure were observed
      in response to betahistine infusions. Pretreatment with thioperamide maleate
      abolished these changes at low doses of betahistine and attenuated the responses
      at higher doses of betahistine. These results show that betahistine
      administration induces increases in vestibular blood flow. These findings support
      the potential use of betahistine for treatment of vestibular disorders, which may
      be caused by compromised circulation.

PMID- 10064647
TI  - Comparison of 3 different anesthetic techniques on 24-hour recovery after
      otologic surgical procedures.
AB  - Intravenous propofol anesthesia is better than inhalational anesthesia for
      otologic surgery, but cost and intraoperative movement make this technique
      prohibitive. This study compares a propofol sandwich anesthetic with a total
      propofol or inhalational anesthetic for otologic surgery to determine which
      produces the best perioperative conditions and least expense. One hundred twenty
      patients undergoing ear surgery were randomly chosen to receive an anesthetic
      with either isoflurane (INHAL), total propofol (TPROP), or propofol used in
      conjunction with isoflurane (PSAND). Postoperative wakeup and the incidence and
      severity of nausea, vomiting, and pain were compared among groups. Antiemetic
      administration and discharge times from recovery and the hospital were also
      compared. The groups were similar, but anesthesia times were longer in the INHAL
      group. Emergence from anesthesia after PSAND or TPROP was more rapid than after
      INHAL. Recovery during the next 24 hours was associated with less nausea and
      vomiting with PSAND than with INHAL. The cost of the PSAND anesthetic was similar
      to that of INHAL, and both were less than TPROP. PSAND anesthesia may be similar
      to TPROP and better than INHAL for otologic procedures. PSAND was less expensive
      than TPROP and produced a similar recovery profile and antiemetic effect in the
      24-hour period after surgery.

PMID- 10064648
TI  - Behaviors of bulbar respiratory interneurons during fictive swallowing and
      vomiting.
AB  - Behaviors of the same individual medullary respiratory interneurons were examined
      during both swallowing and vomiting. In 8 decerebrated and paralyzed cats, 18
      neurons having either augmenting expiratory (E-AUG), decrementing expiratory (E
      DEC), decrementing inspiratory (I-DEC), or constant inspiratory (I-CON) firing
      patterns were recorded near the most rostral part of the nucleus ambiguus. All
      neurons exhibited elementary reflexes to single-shock stimulation of the superior
      laryngeal nerve. During fictive swallowing elicited by superior laryngeal nerve
      stimulation, all neurons were basically inactive. During fictive vomiting induced
      by vagal stimulation and/or emetic drugs, all E-AUG and E-DEC neurons tested
      either were silent or fired weakly between successive retches, whereas I-DEC and
      I-CON neurons tested exhibited burst activity during the retching and early
      expulsion phases. These results indicate that these bulbar respiratory neurons,
      which may be involved in respiratory rhythmogenesis, are multifunctional neurons
      that could also be involved in vomiting but not likely in swallowing.

PMID- 10064649
TI  - Current status of electronystagmography testing.
AB  - ENG testing, whether computerized or not, remains the most useful means of
      assessing the vestibular system. The caloric test provides invaluable site-of
      lesion information that objectively documents a peripheral vestibular lesion.
      Double (bithermal) caloric irrigation of each ear provides a more thorough and
      wider range test of inner ear function than a single caloric irrigation because
      the vestibular system is both excited and inhibited, causing responses in
      opposite directions, which are important in evaluating patients with underlying
      spontaneous nystagmus. In an age in which economically efficient and clinically
      effective diagnostic methods are in high demand, ENG testing remains the gold
      standard of vestibular function tests.

PMID- 10064650
TI  - Physical and psychosocial correlates of head and neck cancer: a review of the
      literature.
AB  - This article reviews recent literature on the physical and psychosocial
      correlates of head and neck cancer, with a focus on quality-of-life issues,
      rehabilitation outcomes, and changes in the literature from the previous decade.
      These studies have shown that head and neck cancer has an enormous impact on the
      quality of life of patients. The most important physical symptoms are speech
      problems, dry mouth and throat, and swallowing problems. Pain is also frequently
      reported. Disturbances in psychosocial functioning and psychological distress are
      reported by a considerable number of patients; worry, anxiety, mood disorder,
      fatigue, and depression are the main symptoms. Cancer of the head and neck has a
      negative effect on social, recreational, and sexual functioning. Despite a
      growing number of longitudinal studies, little is known about the rehabilitation
      outcomes over a longer period of time. Future research is necessary to form a
      consensus about the further development and use of specific instruments to study
      patients with cancer of the head and neck, to conduct more prospective studies,
      and to develop programs that are aimed at maximizing rehabilitation outcomes and
      evaluate these programs with randomized designs.

PMID- 10064651
TI  - Malleus-to-footplate prosthetic interposition: experience with 265 patients.
AB  - Absence of the long process of the incus with or without absence of the stapes
      head accounts for more than 80% of ossicular discontinuities. Total or partial
      replacement prostheses, made of various materials, are interposed to restore the
      transfer function of the middle ear. To simplify ossicular reconstruction, reduce
      operative times and costs, improve functional outcomes, and avoid the risk of
      infections, we have adopted, during the past 10 years, a technique that makes use
      of a personally designed alloplastic prosthetic device. The prosthesis connects
      the malleus to the footplate, even in the presence of the stapes superstructure.
      This malleus-to-footplate prosthesis consists in a plastipore-coated steel piston
      and hydroxyapatite head, complete with a groove. The groove is placed beneath the
      malleus neck after dissection of the tensor tympani tendon and the shaft of the
      piston on the footplate. Two hundred ninety primary ossiculoplasties with the
      malleus-to-footplate prostheses were performed in 265 patients from 1986 to 1995
      in the ENT Department of the University of Verona. The average postoperative air
      bone gap at 0.5 to 3 kHz was 11 dB at 1 year and 14 dB at 5 years. These outcomes
      are significantly better than those personally obtained previously with ossicular
      or alloplastic prostheses. No extrusions occurred. The structural characteristics
      of the malleus-to-foot-plate prosthesis endow the prosthesis with a high degree
      of biocompatibility and stability and optimal sound-transfer function. The
      rationale for this particular ossiculoplasty procedure is discussed.

PMID- 10064652
TI  - Giant esophageal fibrolipoma.

PMID- 10064653
TI  - Intubation granuloma in a neonate.

PMID- 10064654
TI  - Changes in laryngeal muscle activities during hypercapnia in the cat.

PMID- 10064655
TI  - Treatment of urea cycle disorders.

PMID- 10064656
TI  - Leukotriene receptor antagonist treatment of asthma: are we there yet?

PMID- 10064657
TI  - The long- and short-term outcome of living-donor liver transplantation.

PMID- 10064658
TI  - Cisapride doesn't work? Don't go breakin' my heart!

PMID- 10064659
TI  - Expanding role of bisphosphonate therapy in children.

PMID- 10064660
TI  - Neonatal onset ornithine transcarbamylase deficiency: A retrospective analysis.
AB  - OBJECTIVE: A retrospective analysis of 74 cases of neonatal-onset ornithine
      transcarbamylase (OTC) deficiency. METHODS: The medical records of 74 of the 128
      male patients referred to this center with neonatal onset OTC from 1976 to 1996
      were available and analyzed. RESULTS: Initial symptoms of OTC deficiency were
      nonspecific and included feeding difficulties, lethargy, and "respiratory
      distress"; vomiting was infrequent. Respiratory alkalosis was regularly observed;
      the mean pH and pCO2 were 7.5 and 24 torr, respectively. Early consideration of a
      metabolic disorder in those neonates with a negative family history was only 9%.
      Sepsis was initially misdiagnosed in 50% of the cases. For all patients the mean
      age at onset was 63 hours. Survival was better among those who had later onset,
      later diagnostic studies, and diagnosis. Apart from 1 patient whose peak ammonium
      level was 400 micromol/L, all surviving patients had severe developmental delay.
      CONCLUSIONS: OTC deficiency should be suspected in term infants who have early
      signs of encephalopathy, particularly after the first 24 hours; a respiratory
      alkalosis is pathognomic of urea cycle disorders. Severe developmental delay is
      the usual outcome of OTC deficiency.

PMID- 10064661
TI  - The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced
      bronchoconstriction in children.
AB  - OBJECTIVE: To determine the effects of zafirlukast on exercise-induced
      bronchoconstriction in children. STUDY DESIGN: Exercise challenges were done 4
      hours after single oral doses of zafirlukast or placebo were administered in
      asthmatic children (6 to 14 years) treated with beta 2-agonists alone. Subjects
      randomized to treatment had a >/=20% decrease in forced expiratory volume in 1
      second (FEV1 ) after a screening challenge. In a randomized, double-blind, 3-way,
      crossover design, group 1 (n = 20) received placebo and 5 and 20 mg zafirlukast,
      and group 2 (n = 19) received placebo and 10 and 40 mg zafirlukast. Maximal
      percentage fall in FEV1, area under the curve, and time to recovery of FEV1 to
      within 5% of baseline after the challenge were compared with analysis of
      variance. RESULTS: Mean values for maximal fall in FEV1 ranged from -8.7% +/-
      1.7% to -11.1% +/- 1.9% after zafirlukast compared with -17.1% +/- 1.8% and 
      16.3% +/- 1.9% after placebo. Differences from placebo for fall in FEV1 and area
      under the curve were significant (P </=.05) after 5, 20, and 40 mg zafirlukast
      and approached significance (P </=.08) after 10 mg zafirlukast. After all
      zafirlukast doses, recovery times (means of 5 to 7 minutes) decreased
      significantly (P </=.05) and by approximately half compared with placebo (11 and
      14 minutes). Safety assessments did not differ among treatments. CONCLUSION: Four
      hours after dosing, zafirlukast attenuated exercise-induced bronchoconstriction
      in children.

PMID- 10064662
TI  - Pediatric liver transplantation with cadaveric or living related donors:
      comparative results in 90 elective recipients of primary grafts.
AB  - STUDY DESIGN: Between July 1993 and March 1997, 110 children were listed for
      primary elective liver transplantation with cadaveric (Cad: n = 68) or living
      related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and
      surgical and immunologic complications were retrospectively compared in both
      groups. RESULTS: The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of
      42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1
      year patient and graft survival rates were 87% and 75% in the Cad group (n = 49)
      versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of
      post-transplant complications was as follows: hepatic artery thrombosis (Cad:
      16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary
      complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute
      rejection was similar in both groups; however, a lower incidence of acute
      rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS:
      The introduction of an LR donor liver transplantation program allowed a
      significant decrease in the pretransplant mortality rate, with a consequent
      overall improvement in patient survival compared with the Cad series. The
      incidence of biliary complications was higher in the LR series, whereas better
      human leukocyte antigen matching in this subgroup did not result in a lower
      rejection incidence.

PMID- 10064663
TI  - Cisapride in the control of symptoms in infants with gastroesophageal reflux: A
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of cisapride in the treatment of
      uncomplicated gastroesophageal reflux in children younger than 36 months of age.
      STUDY DESIGN: A total of 95 patients satisfied the entry criteria and were
      randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2
      mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week
      treatment period, symptom diary and parental evaluation with repeat 24-hour pH
      study were performed. RESULTS: Sixty-eight patients completed the trial (38 in
      the cisapride group and 30 in the placebo group). There were no significant
      differences in the symptoms of crying, vomiting, or gagging; the overall symptom
      intensity score; or parental global evaluations. There was a significant
      difference (P <.03) in the percent time pH <4, the number of reflux episodes
      lasting more than 5 minutes, and the duration of the longest episode. No
      significant difference was demonstrated for the number of episodes with pH <4 or
      the reflux score. CONCLUSIONS: Cisapride was no better than placebo for relief of
      symptoms in children with uncomplicated gastroesophageal reflux. A beneficial
      effect was demonstrated in the cisapride group in relation to the measured
      parameters for esophageal acid exposure time.

PMID- 10064664
TI  - Randomized trial of "slow" versus "fast" feed advancements on the incidence of
      necrotizing enterocolitis in very low birth weight infants.
AB  - OBJECTIVE: To determine whether the rate of feed advancement affects the
      incidence of necrotizing enterocolitis (NEC). STUDY DESIGN: Prospective
      randomized controlled trial involving 185 formula-fed infants with birth weight
      501 to 1500 g and gestational age </=34 weeks. Infants were randomized into 2
      groups: "slow" (n = 98), who received 15 cc/kg/d increments (a 10-day schedule to
      full feeds) and "fast" (n = 87), who received 35 cc/kg/d increments (a 5-day
      schedule to full feeds) of Similac Special Care 20 cal/oz. Feeds were increased
      only if well tolerated as defined by a protocol. RESULTS: The incidence of NEC
      (Bell stage >/=II) was similar in both groups (slow 13% and fast 9%, P =.5). The
      incidence of perforation (Bell stage III) was also similar in both groups (slow
      4% and fast 2%, P =.8). Feeds were started at a comparable postnatal age in both
      groups (median age: slow 5 days and fast 4 days, P =.9). Although the neonates in
      the fast group attained full enteral intake earlier (median days [25th and 75th
      percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P <.001) and regained their
      birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P <.05), their ages
      at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29,
      62], P =.3) CONCLUSIONS: A greater than twofold difference in the rate of feed
      advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC >/=
      stage II. Factors other than feed advancement appear to be more important in the
      pathogenesis or progression of NEC.

PMID- 10064665
TI  - Maternal periconceptional alcohol consumption and risk for orofacial clefts.
AB  - OBJECTIVE: To investigate whether periconceptional maternal alcohol consumption
      increased the risk of delivering infants with orofacial cleft phenotypes. DESIGN:
      Data were derived from a large population-based case control study of fetuses and
      infants among a cohort of California births from 1987 to 1989 (n = 548,844).
      Information concerning alcohol consumption was obtained by telephone interviews
      with mothers of 731 infants (84.7% of eligible) with orofacial clefts and of 734
      (78.2%) infants in a nonmalformed control group. RESULTS: Thirty-nine percent of
      mothers in the case group and 42% of mothers in the control group reported that
      they consumed alcohol during the period 1 month before through 3 months after
      conception. Relative to nonconsumers, women who reported alcohol consumption
      (<weekly, weekly, or daily) were not at substantially increased risk of
      delivering infants with any cleft phenotype. However, for women who reported
      weekly or more frequent episodes of consuming >/=5 drinks per drinking occasion
      compared with those who did not, we observed increased risks for isolated (no
      other major congenital anomaly) cleft lip with or without cleft palate, odds
      ratio = 3.4 (95% confidence interval, 1.1 to 9.7); multiple cleft lip with or
      without cleft palate, odds ratio = 4.6 (1. 2 to 18.8); and "known syndrome"
      clefts, odds ratio = 6.9 (1.9 to 28. 6). Adjustment for maternal cigarette
      smoking, race, education, or vitamin use did not substantially change observed
      risks. CONCLUSION: We observed a lack of increased risks of clefts for relatively
      low quantities of maternal alcohol consumption and increased risks of clefts for
      higher quantities of maternal alcohol consumption.

PMID- 10064666
TI  - Postsplenectomy course in homozygous sickle cell disease.
AB  - OBJECTIVE: To determine whether children with homozygous sickle cell (SS) disease
      and splenectomy are at greater risk of death, overwhelming septicemia, or other
      complications. METHODS: A total of 130 patients with SS treated by splenectomy
      (46 recurrent acute splenic sequestration, 84 chronic hypersplenism) over a 22.5
      year period at the Sickle Cell Clinic of the University Hospital of the West
      Indies, Kingston, Jamaica, were compared with a control group matched for sex,
      age, and duration of follow-up in a retrospective review. Deaths and bacteremias
      were examined over the whole study period. Painful crises, acute chest syndromes,
      and febrile episodes were compared in the 90 patients completing 5 years of
      postsplenectomy follow-up. FINDINGS: Mortality and bacteremic episodes did not
      differ between the splenectomy and control groups. Painful crises were more
      common in the splenectomy group than in the control group (P =.01) but did not
      differ between splenectomy indications. Acute chest syndrome was more common in
      the splenectomy group than in the control group (P <.01) and was more common in
      the acute splenic sequestration group than in the hypersplenism group (P =.01).
      Febrile events did not differ between the groups or between the indications for
      splenectomy. CONCLUSION: Splenectomy does not increase the risk of death or
      bacteremic illness in patients with SS disease and, if otherwise indicated,
      should not be deferred for these reasons.

PMID- 10064667
TI  - Factor V Leiden and other hypercoagulable state mutations are not associated with
      osteonecrosis during or after treatment for pediatric malignancy.
AB  - OBJECTIVE: Osteonecrosis (ON) is a debilitating complication of cancer treatment
      in children and is usually associated with systemic steroid therapy. Defects of
      coagulation may be important in the pathogenesis of ON. This study evaluated the
      prevalence of factor V Leiden (FVL, 1691G-->A), the most common inherited
      thrombophilic state, the prothrombin 20210G-->A polymorphism, and the
      thermolabile methylene tetrahydrofolate reductase (MTHFR, 677C-->T) variant in a
      group of children in whom ON developed during or after treatment for cancer.
      STUDY DESIGN: Children in whom ON developed during cancer treatment at St Jude
      Children's Research Hospital were studied (n = 24). Genomic DNA was isolated, and
      polymerase chain reaction was performed to identify the FVL, prothrombin 20210,
      and thermolabile MTHFR mutations. RESULTS: Sixteen of 24 patients had acute
      lymphoblastic leukemia. The mean age at ON diagnosis was 14.4 +/- 3. 7 years. The
      mean interval between cancer diagnosis and ON diagnosis was 27 +/- 21 months.
      Twenty-two patients had received steroids for a mean duration of 24 +/- 15 weeks
      before having development of ON. No patient had a history of thrombosis. Five
      (21%) patients had a family history of thrombosis. Genetic analysis revealed 0
      (0%) of 24 FVL, 1 (4.5%) of 22 prothrombin 20210, and 3 (13.6%) of 22
      thermolabile MTHFR. None of these mutation frequencies was significantly
      different from our control frequencies or published values. CONCLUSIONS: Although
      procoagulant abnormalities in general and FVL in particular have been detected in
      a significant number of patients with ON of the jaw and Legg-Perthes disease, we
      did not identify an increased prevalence of FVL or other hypercoagulable state
      mutations in a cohort of children with ON that developed during or after
      treatment for a variety of cancers.

PMID- 10064668
TI  - Increased incidence of cancer in patients with cartilage-hair hypoplasia.
AB  - OBJECTIVE: Previous reports have suggested an increased risk of cancer among
      patients with cartilage-hair hypoplasia (CHH). This study was carried out to
      further evaluate this risk among patients with CHH and their first-degree
      relatives. STUDY DESIGN: One hundred twenty-two patients with CHH were identified
      through 2 countrywide epidemiologic surveys in 1974 and in 1986. Their parents
      and nonaffected siblings were identified through the Population Register Center.
      This cohort underwent follow-up for cancer incidence through the Finnish Cancer
      Registry to the end of 1995. RESULTS: A statistically significant excess risk of
      cancer was seen among the patients with CHH (standardized incidence ratio 6.9,
      95% confidence interval 2.3 to 16), which was mainly attributable to non
      Hodgkin's lymphoma (standardized incidence ratio 90, 95% confidence interval 18
      to 264). In addition, a significant excess risk of basal cell carcinoma was seen
      (standardized incidence ratio 35, 95% confidence interval 7.2 to 102). The cancer
      incidence among the siblings or the parents did not differ from the average
      cancer incidence in the Finnish population. CONCLUSIONS: This study confirms an
      increased risk of cancer, especially non-Hodgkin's lymphoma, probably
      attributable to defective immunity, among patients with CHH.

PMID- 10064669
TI  - Transdermal fentanyl in children with cancer pain: feasibility, tolerability, and
      pharmacokinetic correlates.
AB  - OBJECTIVES: (1) To assess the feasibility and tolerability of the therapeutic
      transdermal fentanyl system (TTS-fentanyl) by using a clinical protocol developed
      for children with cancer pain. (2) To estimate the pediatric pharmacokinetic
      parameters of TTS-fentanyl. METHODS: The drug was administered in open-label
      fashion; and measures of analgesia, side effects, and skin changes were obtained
      for a minimum of 2 doses (6 treatment days). Blood specimens were analyzed for
      plasma fentanyl concentrations. The pharmacokinetics of TTS-fentanyl were
      estimated by using a mixed effect modeling approach. RESULTS: Treatment was well
      tolerated. Ten of the 11 patients who completed the 2 doses continued treatment
      with TTS-fentanyl. The duration of treatment ranged from 6 to 275 days. The time
      to reach peak plasma concentration ranged from 18 hours to >66 hours in patients
      receiving the 25 microg/h patch. Compared with published pharmacokinetic data
      from adults, the mean clearance and volume of distribution of transdermal
      fentanyl were the same, but the variability was less. CONCLUSIONS: Treatment of
      children with TTS-fentanyl is feasible and well tolerated and yields fentanyl
      pharmacokinetic parameter estimates similar to those for adults. A larger study
      is required to confirm these findings and further test the clinical protocol.

PMID- 10064670
TI  - Interferons and cerebral palsy.
AB  - OBJECTIVE: To explore the association of neonatal interferons (IFNs) with spastic
      cerebral palsy (CP) and with other measured substances. STUDY DESIGN: Assays of
      archived neonatal blood of 31 predominantly term children with CP and 65 children
      in a control group were obtained by recycling immunoaffinity chromatography with
      laser-enhanced fluorescence and chemiluminescence detection. RESULTS: Fourteen of
      31 children with spastic CP had concentrations of IFNs-alpha, beta, and gamma
      exceeding any control. Levels of interleukins-1, 6, 8, tumor necrosis factor
      alpha, chemokines, colony stimulating factors, transforming growth factor-beta,
      complement components and regulators, certain neuropeptides, and thyroid hormones
      also differed from control levels in these 14 children. The 17 children with CP
      whose IFN concentrations were within the control range had levels of inflammatory
      cytokines higher than but near to control values; 13 of these 17 had values for
      coagulation factors that exceeded control values. Seven of 9 children with
      spastic diplegia had high IFNs, and 8 of 10 hemiplegic children had normal IFNs.
      CONCLUSION: Neonatal IFNs exceeding control concentrations were associated with
      other biochemical and clinical indicators of inflammation and with spastic
      diplegia. In these children with CP, IFNs within the control range were
      associated with concentrations of other inflammatory markers that were near to
      control values and with spastic hemiplegia.

PMID- 10064671
TI  - The natural history of microalbuminuria in adolescents with type 1 diabetes.
AB  - OBJECTIVE: To describe the natural history of urinary albumin excretion measured
      initially during the first decade of type 1 diabetes in adolescents and to
      identify predictors of the onset and progression of microalbuminuria (MA) in this
      population. STUDY DESIGN: A retrospective cohort follow-up study was done on 76
      adolescents whose albumin excretion rate (AER) had been determined in the first
      decade of their diabetes. Subjects were monitored for a mean of 6 years after
      initial AER testing. Those with MA were compared with a group with similar age,
      sex, and diabetes duration who initially had normoalbuminuria (NA). RESULTS: Of
      the 28 with initial MA, 9 (32%) regressed (8 to within the NA range), whereas MA
      was persistent in 10 (36%) and progressed in 9 (32%), 5 to overt proteinuria. Of
      the 47 who had initial NA, MA developed in 14 (30%) and overt proteinuria in 3
      (6%). With MA status at follow-up as the dependent variable, multiple regression
      analysis showed that initial AER (P =.0002) and hemoglobin A1c (P =.02) measured
      at the same time were significant independent variables. CONCLUSIONS: These data
      suggest that in adolescents: (1) MA detected in the first decade of disease will
      persist or progress in the second decade in approximately two thirds of patients,
      and new MA will develop in a third of those initially normoalbuminuric; and (2)
      the appearance, persistence, or progression of MA is influenced in large part by
      metabolic control assessed by hemoglobin A1c both at initial MA screening and
      throughout the course of diabetes. This underlines the need for MA screening
      starting early in the course of type 1 diabetes in adolescents and for
      maintenance of good metabolic control.

PMID- 10064672
TI  - Halitosis in children.
AB  - OBJECTIVE: To determine the relationship between oral parameters and halitosis in
      children whose parents complained of malodorous breath. METHODS: Twenty-four
      children (ages 5 to 14) were examined at 3 appointments. After the second
      appointment oral hygiene instructions were given. Malodor-related parameters
      included odor judge scores (whole mouth, tongue, nose, and interdental areas),
      sulfide levels, and microbiologic tests (Oratest and BANA). Dental-related
      parameters included plaque index, dental index (DMFT), food impaction, bleeding,
      and tongue coating. Statistical analyses included analysis of variance, paired t
      tests, Pearson correlations, and multiple regression. RESULTS: Whole mouth odor
      was significantly associated with plaque index levels (r = 0.64, P =.001) and
      Oratest (r = -0.57, P =.003). Whole mouth malodor was significantly associated
      with tongue dorsum posterior odor (r = 0.641, P =.001) and was higher in subjects
      with interdental odor (P =.003). Tongue odor was also significantly associated
      with nasal malodor (r = 0.57; P =.004). Sulfide levels were correlated with oral
      malodor levels only at the second appointment (r = 0.46, P =.02). CONCLUSIONS:
      The data suggest that, as in adults, oral malodor in children is related
      primarily to oral factors. Correlations between nasal and oral malodor were
      evident, suggesting that postnasal drip plays a major role.

PMID- 10064673
TI  - Latex sensitization in spina bifida appears disease-associated.
AB  - OBJECTIVE: The high prevalence of latex sensitization (up to 80%) in patients
      with spina bifida (SB) has been attributed to repeated exposure to latex
      products, whereas disease-associated factors have not been considered. METHODS:
      We compared children with SB (n = 21) and children with posthemorrhagic or
      congenital hydrocephalus (PH, n = 32), all of whom had a ventriculoperitoneal
      shunt since young age. Latex sensitization, number of operations, atopic history,
      and total IgE levels were evaluated. RESULTS: The following characteristics were
      recorded: age (SB: 52 months, range 1 to 264 months; PH: 71 months, range 1 to
      192 months) and mean number of operations (SB: 2. 09; PH: 2.53). Of the SB group,
      43% (9 of 21) showed elevated latex-specific IgE antibodies in contrast to 6% (2
      of 32) in the PH group (P <.01). Latex-specific IgE antibodies were detected by 1
      year of age, and one surgical operation was sufficient to induce latex-specific
      IgE-antibody production in patients with SB. CONCLUSIONS: The results suggest
      that the SB population bears a disease-associated propensity for latex
      sensitization. Sensitization to latex antigens may occur after the very first
      contact, arguing for latex avoidance measures from the very beginning of life.

PMID- 10064674
TI  - Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn.
AB  - Subcutaneous fat necrosis of the newborn (SCFN) is characterized by indurated
      violet skin nodules and, occasionally, life-threatening hypercalcemia. Current
      treatments of patients with SCFN-related hypercalcemia are often only partially
      successful and may be associated with prolonged hypercalcemia. We now report the
      use of etidronate, a bisphosphonate, to control hypercalcemia in an infant with
      SCFN.

PMID- 10064675
TI  - Respiratory chain complex III [correction of complex] in deficiency with
      pruritus: a novel vitamin responsive clinical feature.
AB  - We report a child with an isolated complex III respiratory chain deficiency and
      global developmental delay who had severe pruritus with elevated plasma bile acid
      levels. A liver biopsy showed micronodular cirrhosis, and enzymologic evaluation
      demonstrated an isolated complex III deficiency in both liver and muscle. His
      pruritus improved and serum bile acid levels decreased after treatment with
      menadione and vitamin C.

PMID- 10064676
TI  - Delayed adaptation of the pulmonary hemodynamics in infants with mild to moderate
      meconium aspiration syndrome.
AB  - Early postnatal pulmonary hemodynamic changes were investigated with Doppler
      echocardiography in 17 infants with mild or moderate meconium aspiration syndrome
      (MAS) and 16 healthy infants in a control group. The results indicate that the
      physiologic adaptation of the pulmonary hemodynamics is delayed in mild and
      moderate forms of MAS. Thus infants with clinical evidence of MAS need careful
      cardiovascular monitoring during postnatal circulatory transition.

PMID- 10064677
TI  - Cysteine supplementation results in normalization of plasma taurine
      concentrations in children receiving home parenteral nutrition.
AB  - We evaluated plasma sulfur amino acid concentrations in children with short gut
      syndrome receiving home parenteral nutrition (n = 6). Cysteine HCl addition to
      solutions formulated with a pediatric amino acid product will increase plasma
      taurine concentrations to within the normal reference range.

PMID- 10064678
TI  - Celiac disease-associated alopecia in childhood.
AB  - We report the association of celiac disease and alopecia in 3 children. In one,
      the alopecia developed after 4 years' nonadherence to a gluten-free diet; the
      other 2 patients presented with alopecia. Administration of a gluten-free diet
      resulted in partial regrowth of hair in the first child and complete hair growth
      in the others.

PMID- 10064679
TI  - Fixed drug eruptions in children.
AB  - To determine the anatomic location and offending drug in fixed drug eruptions
      (FDE) in children, we performed a 5-year retrospective analysis. Thirty-five
      children with FDE were evaluated. The most common cause of FDE was the
      combination drug trimethoprim-sulfamethoxazole.

PMID- 10064680
TI  - Adrenal suppression in children with the human immunodeficiency virus treated
      with megestrol acetate.
AB  - Symptoms and laboratory evidence of adrenal suppression developed in 2 children
      with the human immunodeficiency virus after megestrol acetate (MA) therapy was
      discontinued; both required transient glucocorticoid replacement therapy. High
      dose corticotropin stimulation testing performed on children with the human
      immunodeficiency virus treated or not treated with MA showed that baseline and
      post-corticotropin cortisol levels were extremely low in 7 of 10 treated patients
      and normal in 10 of 10 members of a control group (P <.01). MA may suppress
      adrenal function, and replacement glucocorticoids may prevent or relieve
      associated symptoms at times of severe stress or on discontinuation of MA
      therapy.

PMID- 10064681
TI  - Spontaneous growth and bone age development in a patient with 17alpha-hydroxylase
      deficiency: evidence of the role of sexual steroids in prepubertal bone
      maturation.
AB  - A male pseudohermaphrodite with 17alpha-hydroxylase deficiency and complete
      nonvirilization was monitored for excessive weight from the age of 3.5 to 11.5
      years before the absence of sex steroids was detected. The retrospective analysis
      of growth data showed retarded bone age development despite adequate growth,
      which led to a remarkable increase in final height prognosis.

PMID- 10064682
TI  - The "two bag system" for variable intravenous dextrose and fluid administration:
      benefits in diabetic ketoacidosis management.
AB  - 1 case-controlled retrospective analysis compared the "two bag system," based on
      the euglycemic clamp technique, versus the traditional "one bag" method for
      intravenous diabetic ketoacidosis management. The two bag system can provide more
      cost-effective intravenous dextrose and fluid delivery and enhance quality of
      care by improving the efficiency, timeliness, and flexibility of overall control.

PMID- 10064683
TI  - Pseudoscurvy caused by copper deficiency.

PMID- 10064684
TI  - Spastic diplegia and interferon.

PMID- 10064685
TI  - NO effect on hemostasis.

PMID- 10064686
TI  - Neonatal effects of maternal consumption of blue cohosh.

PMID- 10064687
TI  - Growth hormone therapy in Noonan syndrome.

PMID- 10064688
TI  - Authors' Reply:

PMID- 10064689
TI  - Reply 

PMID- 10064690
TI  - Reply 

PMID- 10064691
TI  - Reply 

PMID- 10064692
TI  - Reply 

PMID- 10064693
TI  - Foldability of barnase mutants obtained by permutation of modules or secondary
      structure units.
AB  - Modules, defined as stable, compact structure units in a globular protein, are
      good candidates for the construction of novel foldable proteins by permutation.
      Here we decomposed barnase into six modules (M1-M6) and constructed 23 barnase
      mutants containing permutations of the internal four (M2-M5) out of six modules.
      Globular proteins can also be subdivided into secondary structure units based on
      the extended structures that control the mutual relationships of the modules. We
      also decomposed barnase into six secondary structure units (S1-S6) and
      constructed 21 barnase mutants containing permutations of the internal four (S2
      S5) out of six secondary structure units. Foldability of these two types of
      mutants was assessed by means of circular dichroism, fluorescence, and 1H-NMR
      measurements. A total of 15 of 23 module mutants and 15 of 21 secondary structure
      unit mutants formed definite secondary structures, such as alpha-helix and beta
      sheet, at 20 microM owing to intermolecular interactions, but most of them
      converted to random coil structures at a lower concentration (1 microM). Of the
      44 mutants, only two, M3245 and S2543, gave distinct near-UV CD spectra. S2543
      especially showed definite signal dispersion in the amide and methyl regions of
      the 1H-NMR spectrum, though M3245 did not. Furthermore, urea-induced unfolding of
      S2543 monitored by far-UV CD and fluorescence measurements showed a distinct
      cooperative transition. These results strongly suggest that S2543 takes partially
      folded conformations in aqueous solution. Our results also suggest that building
      blocks such as secondary structure units capable of taking different stable
      conformations by adapting themselves to the surrounding environment, rather than
      building blocks such as modules having a specified stable conformation, are
      required for the formation of foldable proteins. Therefore, the use of secondary
      structure units for the construction of novel globular proteins is likely to be
      an effective approach.

PMID- 10064694
TI  - p53 mutants without a functional tetramerisation domain are not oncogenic.
AB  - p53 is altered in about 50 % of cancers. Most of the p53 mutants have lost the
      wild-type tumour suppressor activity but show oncogenic properties. The majority
      of the p53 alterations are missense mutations of residues located in its DNA
      binding domain (DBD). Only a few mutations concern residues in its
      tetramerisation domain (TD). However, the study of mutant proteins identified in
      tumors that do not form tetramers has shown that they have lost the wild-type
      activity like most of the p53 DBD mutants. Here, we show that two of such mutant
      proteins, Arg342Pro and Leu344Pro are not dominant negative and do not stimulate
      the expression of a reporter gene under the control of the multi-drug resistance
      gene-1 (MDR-1). This suggests that to be oncogenic, p53 mutants need to form
      tetramers. Accordingly, the dominant negative effect and the ability of a
      tetrameric mutant protein, Asp281Gly, to stimulate the MDR-1 promoter are
      abolished when its TD is rendered non-functional by the mutation of leucine 344
      to a proline residue. These results suggest that mutations in the TD, are less
      selected in tumors than mutations in the DBD because they do not lead to
      oncogenic proteins.

PMID- 10064695
TI  - Inversion of thermosensing property of the bacterial receptor Tar by mutations in
      the second transmembrane region.
AB  - The aspartate chemoreceptor Tar of Escherichia coli serves as a warm sensor that
      produces attractant and repellent signals upon increases and decreases in
      temperature, respectively. However, increased levels of methylation of the
      cytoplasmic domain of Tar resulting from aspartate binding convert Tar to a cold
      sensor with the opposite signaling behavior. Detailed analyses of the methylation
      sites, which are located in two separate alpha-helices (MH1 and MH2), have
      suggested that intra- and/or intersubunit interactions of MH1 and MH2 play a
      critical role in thermosensing. These interactions may be influenced by binding
      of aspartate, which could trigger some displacement of MH1 through the second
      transmembrane region (TM2). As an initial step toward understanding the role of
      TM2 in thermosensing, we have examined the thermosensing properties of 43 mutant
      Tar receptors with randomized TM2 sequences (residues 190-210). Among them, we
      identified one mutant receptor (Tar-I2) that functioned as a cold sensor in the
      absence of aspartate. This is the first example of attractant-independent
      inversion of thermosensing in Tar. Further analyses identified the minimal
      essential divergence from the wild-type Tar sequence (Q191V-W192R-Q193C) required
      for the inverted response. Thus, displacements of TM2 seem to influence the
      thermosensing function of Tar.

PMID- 10064696
TI  - Structure and structural variations of the Escherichia coli 30 S ribosomal
      subunit as revealed by three-dimensional cryo-electron microscopy.
AB  - A three-dimensional reconstruction of the 30 S subunit of the Escherichia coli
      ribosome was obtained at 23 A resolution. Because of the improved resolution,
      many more structural details are seen as compared to those obtained in earlier
      studies. Thus, the new structure is more suitable for comparison with the 30 S
      subunit part of the 70 S ribosome, whose structure is already known at a better
      resolution. In addition, we observe relative and, to some extent, independent
      movements of three main structural domains of the 30 S subunit, namely head,
      platform and the main body, which lead to partial blurring of the reconstructed
      volume. An attempt to subdivide the data set into conformationally defined
      subsets reveals the existence of conformers in which these domains have different
      orientations with respect to one another. This result suggests the existence of
      dynamic properties of the 30 S subunit that might be required for facilitating
      its interactions with mRNA, tRNA and other ligands during protein biosynthesis.

PMID- 10064697
TI  - Dual role of DNA intrinsic curvature and flexibility in determining nucleosome
      stability.
AB  - A statistical mechanistic approach to evaluate the sequence-dependent
      thermodynamic stability of nucleosomes is proposed. The model is based on the
      calculation of the DNA intrinsic curvature, obtained by integrating the
      nucleotide step deviations from the canonical B-DNA structure, and on the
      evaluation of the first order elastic distortion energy to reach the nucleosomal
      superstructure. Literature data on the free energy of nucleosome formation as
      obtained by competitive nucleosome reconstitution of a significant pool of
      different DNA sequences were compared with the theoretical results, and a
      satisfactorily good correlation was found. A striking result of the comparison is
      the emergence of two opposite roles of the DNA intrinsic curvature and
      flexibility in determining nucleosome stability. Finally, the obtained results
      suggest that the curvature-dependent DNA hydration should play a relevant role in
      the sequence-dependent nucleosome stability.

PMID- 10064698
TI  - Recognition of the carboxyl-terminal signal for GPI modification requires
      translocation of its hydrophobic domain across the ER membrane.
AB  - A carboxyl-terminal hydrophobic domain is an essential component of the processed
      signal for attachment of the glycosyl-phosphatidylinositol (GPI) membrane anchor
      to proteins and it is linked to the site (omega) of GPI modification by a spacer
      domain. This study was designed to test the hypothesis that the hydrophobic
      domain interacts with the lipid bilayer of the endoplasmic reticulum (ER)
      membrane to optimally position the omega site for GPI modification. The
      hydrophobic domain of the GPI signal in the human folate receptor (FR) type alpha
      was substituted with the carboxyl-terminal segment of the low-density lipoprotein
      receptor (LDLR), including its membrane spanning region, without altering either
      the spacer or the omega site. The FR-alpha/LDLR chimera was not GPI modified but
      was attached to the plasma membrane by a polypeptide anchor. When the carboxyl
      terminal half of the hydrophobic transmembrane polypeptide in the FR-alpha/LDLR
      chimera was altered by introduction of negatively charged (Asp) residues, or when
      the cytosolic domain in the chimera was deleted, the mutated proteins became GPI
      anchored. On the other hand, attachment of a carboxyl-terminal segment of LDLR
      including the entire cytosolic domain to FR-alpha converted it into a
      transmembrane protein. The results indicate that in the FR-alpha/LDLR chimera the
      inability of the cellular machinery for GPI modification to recognize the
      hydrophobic domain is not due to the intrinsic nature of the peptide, but is
      rather due to the retention of the peptide within the lipid bilayer. It follows
      that the hydrophobic domain in the signal for GPI modification must traverse the
      ER membrane prior to recognition of the omega site by the GPI-protein
      transamidase. The results thus establish a critical topographical requirement for
      recognition of the GPI signal in the ER.

PMID- 10064699
TI  - MADS-box transcription factors adopt alternative mechanisms for bending DNA.
AB  - Transcription factor-induced DNA bending is important in determining local
      promoter architecture and it is thought to be a key determinant of their
      function. The human MADS-box transcription factors serum response factor and
      MEF2A exhibit different propensities to bend their binding sites. Here, we have
      investigated the ability of several family members from different species to bend
      DNA and the molecular mechanisms underlying this process. Differential DNA
      bending is observed in yeast and plant MADS-box proteins. Like MEF2A, the yeast
      proteins Rlm1 and Smp1 exhibit low DNA bending propensities. A comparison of
      serum response factor and SQUA reveals that the basic mechanisms of DNA bending
      appear to be conserved between these proteins, although several key differences
      do exist. In contrast to serum response factor, SQUA bends DNA in a DNA sequence
      dependent manner. In both proteins, protein-DNA contacts made between residues in
      the beta-loop and the N-terminal end of the recognition helices in the MADS-box
      are the major determinants of DNA bending. However, although residues which are
      involved in DNA bending are predicted to be located in similar positions in their
      tertiary structures, different residues dictate bending by each protein. Further
      complexities are uncovered in the links between the DNA bending propensity and
      the binding specificity. In combination with structural studies, our results
      provide a model to explain how differential bending by MADS-box proteins is
      achieved at the molecular level and provide insights into how this might affect
      their biological function.

PMID- 10064700
TI  - Site-directed mutants of RTP of Bacillus subtilis and the mechanism of
      replication fork arrest.
AB  - DNA replication fork arrest during the termination phase of chromosome
      replication in Bacillus subtilis is brought about by the replication terminator
      protein (RTP) bound to specific DNA terminator sequences (Ter sites) distributed
      throughout the terminus region. An attractive suggestion by others was that
      crucial to the functioning of the RTP-Ter complex is a specific interaction
      between RTP positioned on the DNA and the helicase associated with the
      approaching replication fork. In support of this was the behaviour of two site
      directed mutants of RTP. They appeared to bind Ter DNA normally but were
      ineffective in fork arrest as ascertained by in vitro Escherichia coli DnaB
      helicase and replication assays. We describe here a system for assessing the fork
      arrest behaviour of RTP mutants in a bona fide in vivo assay in B. subtilis. One
      of the previously studied mutants, RTP.Y33N, was non-functional in fork arrest in
      vivo, as predicted. But through extensive analyses, this RTP mutant was shown to
      be severely defective in binding to Ter DNA, contrary to expectation. Taken in
      conjunction with recent findings on the other mutant (RTP.E30K), it is concluded
      that there is as yet no substantive evidence from the behaviour of RTP mutants to
      support the RTP-helicase interaction model for fork arrest. In an extension of
      the present work on RTP.Y33N, we determined the dissociation rates of complexes
      formed by wild-type (wt) RTP and another RTP mutant with various terminator
      sequences. The functional wtRTP-TerI complex was quite stable (half-life of 182
      minutes), reminiscent of the great stability of the E. coli Tus-Ter complex. More
      significant were the exceptional stabilities of complexes comprising wtRTP and an
      RTP double-mutant (E39K.R42Q) bound to some particular terminator sequences. From
      the measurement of in vivo fork-arrest activities of the various complexes, it is
      concluded that the stability (half-life) of the whole RTP-Ter complex is not the
      overriding determinant of arrest, and that the RTP-Ter complex must be actively
      disrupted, or RTP removed, by the action of the approaching replication fork.

PMID- 10064701
TI  - An experimental study of mechanism and specificity of peptide nucleic acid (PNA)
      binding to duplex DNA.
AB  - We investigated the mechanism and kinetic specificity of binding of peptide
      nucleic acid clamps (bis-PNAs) to double-stranded DNA (dsDNA). Kinetic
      specificity is defined as a ratio of initial rates of PNA binding to matched and
      mismatched targets on dsDNA. Bis-PNAs consist of two homopyrimidine PNA oligomers
      connected by a flexible linker. While complexing with dsDNA, they are known to
      form P-loops, which consist of a [PNA]2-DNA triplex and the displaced DNA strand.
      We report here a very strong pH-dependence, within the neutral pH range, of
      binding rates and kinetic specificity for a bis-PNA consisting of only C and T
      bases. The specificity of binding reaches a very sharp and high maximum at pH
      6.9. In contrast, if all the cytosine bases in one of the two PNA oligomers
      within the bis-PNA are replaced by pseudoisocytosine bases (J bases), which do
      not require protonation to form triplexes, a weak dependence on pH of the rates
      and specificity of the P-loop formation is observed. A theoretical analysis of
      the data suggests that for (C+T)-containing bis-PNA the first, intermediate step
      of PNA binding to dsDNA occurs via Hoogsteen pairing between the duplex target
      and one oligomer of bis-PNA. After that, the strand invasion occurs via Watson
      Crick pairing between the second bis-PNA oligomer and the homopurine strand of
      the target DNA, thus resulting in the ultimate formation of the P-loop. The data
      for the (C/J+T)-containing bis-PNA show that its high affinity to dsDNA at
      neutral pH does not seriously compromise the kinetic specificity of binding.
      These findings support the earlier expectation that (C/J+T)-containing PNA
      constructions may be advantageous for use in vivo.

PMID- 10064702
TI  - U3 small nucleolar RNA is essential for cleavage at sites 1, 2 and 3 in pre-rRNA
      and determines which rRNA processing pathway is taken in Xenopus oocytes.
AB  - A molecular dissection of U3 small nucleolar RNA (snoRNA) was performed in vivo
      in Xenopus oocytes and the effects on rRNA processing were analyzed. Oocyte
      injection of antisense oligonucleotides against parts of U3 snoRNA resulted in
      specific fragmentation of U3 by endogenous RNase H. Fragmentation of U3 domain II
      correlated with a decrease in 20 S pre-rRNA and a concomitant increase in 36 S
      pre-rRNA, indicating reduced cleavage at site 3. Conversely, fragmentation of U3
      domain I completely blocked 18 S rRNA formation, increased the 20 S rRNA
      precursor, and decreased 36 S pre-rRNA, indicating inhibition of cleavage at
      sites 1+2. rRNA processing defects at sites 1+2 or 3 after destruction of intact
      endogenous U3 snoRNA were rescued by injection of in vitro transcripts of U3
      snoRNA or certain U3 fragments. Thus, cleavage at sites 1+2 and 3 is U3 snoRNA
      dependent. Moreover, U3 snoRNA has two functional modules: domain I for sites 1+2
      cleavage and domain II for site 3 cleavage. The data suggest that whichever of
      these U3 domains acts first determines which rRNA processing pathway will be
      taken: cleavage first at site 3 of pre-rRNA leads to pathway A, whereas cleavage
      first at sites 1+2 leads to pathway B for rRNA processing. Predictions of this
      model were validated by rescue of site 3 cleavage by injection of just domain II
      after U3 depletion. Rescue of sites 1+2 cleavage required covalent continuity of
      domain I with the hinge region and non-covalent association with domain II. We
      could experimentally shift which rRNA processing pathway was taken by injecting
      fragments of U3 to compete with endogenous U3 snoRNA.

PMID- 10064703
TI  - A three-way junction and constituent stem-loops as the stimulator for programmed 
      1 frameshifting in bacterial insertion sequence IS911.
AB  - Several signals are required for the programmed frameshifting in translation of
      IS911 mRNA. These include a Shine Dalgarno (SD)-like sequence, a slippery
      sequence of six adenine residues and a guanine residue (A6G) and a 3' secondary
      structure. The structure of the mRNA containing these elements was investigated
      using chemical and enzymatic probing. The probing data show that the 3' structure
      is a three-way junction of stems. The function of the three-way junction was
      investigated by mutagenesis. Disrupting the stability of the structure greatly
      affects frameshifting and transposition levels as tested by separate in vivo
      assays. Structural probing and thermal melting profiles indicate that the
      disrupted three-way junctions have altered structures.

PMID- 10064704
TI  - Asymmetric recognition of psoralen interstrand crosslinks by the nucleotide
      excision repair and the error-prone repair pathways.
AB  - Psoralen is an asymmetric photoreactive intercalator with a furane and a pyrone
      side. When intercalated at 5'-TpA-3' sites and upon UVA irradiation, the psoralen
      can react with the thymine residues on both strands, introducing an interstrand
      crosslink. Using psoralen-coupled triple-helix-forming oligonucleotides, psoralen
      interstrand crosslinks can be site-specifically introduced in the coding sequence
      of URA3, a yeast auxotrophic marker carried on plasmid vectors. In addition,
      crosslinks introduced via a triple-helix-forming oligonuleotide are oriented with
      the furane side of the psoralen associated with a specific strand of the target
      sequence. Here, the transformation efficiency, the mutation frequency and the
      mutational spectra of site-specifically placed and oriented crosslinks were
      examined in yeast cells. We found that the nature of the targeted mutations
      depended on the crosslink orientation: bypass of the pyrone-adducted thymine
      yielded T-->A or T-->C substitutions and A insertions, while bypass of the furane
      adducted thymine yielded T-->G substitutions and G insertions. Thus, the
      structure of the damage strongly influences the choice of the nucleotide
      incorporated during translesion synthesis. In addition, the observed pattern of
      mutagenesis suggests a coupling to transcription, similar to the one observed in
      mammalian cells. Finally, the substitutions affected only the coding strand when
      the pyrone link of the psoralen crosslink was on this strand, whereas they
      affected both strands when the pyrone link was on the transcribed strand,
      suggesting that the incision preference of psoralen crosslinks, which has been
      observed with purified uvrABC proteins in bacteria, is conserved in live
      eucaryotic cells.

PMID- 10064705
TI  - Structural and electrophysiological effects of local anesthetics and of low
      temperature on myelinated nerves: implication of the lipid chains in nerve
      excitability.
AB  - X-ray scattering and electrophysiological experiments performed on toad sciatic
      nerves as a function of the exposure to either low temperature or tetracaine
      yielded the following results: (i) the main structural effect is to thicken the
      individual membranes, thus to stiffen the acyl chains and increase the repeat
      distance of the one-dimensional lattice, phenomena that are typical of lipid
      containing systems with disordered chains; (ii) the electrophysiological effect
      is to decrease the amplitude and velocity of the compound action potential; (iii)
      the structural and physiological effects of the two agents are practically
      identical. Since the structural and the electrophysiological parameters have
      different origins in the nerves (the structure regards the myelin sheath, the
      electrical signals originate at the nodes of Ranvier) it is inferred that
      tetracaine and low temperature exert similar effects on the membranes of both the
      myelin sheath and the nodes of Ranvier. Also, since local anesthetics act by
      inhibiting the Na+ channels, these observations suggest that the acyl chain
      conformation modulates the channel function and thus the generation of action
      potential.

PMID- 10064706
TI  - Characterization of distinct early assembly units of different intermediate
      filament proteins.
AB  - We have determined the mass-per-length (MPL) composition of distinct early
      assembly products of recombinant intermediate filament (IF) proteins from the
      four cytoplasmic sequence homology classes, and compared these values with those
      of the corresponding mature filaments. After two seconds under standard assembly
      conditions (i.e. 25 mM Tris-HCl (pH 7.5), 50 mM NaCl, 37 degrees C), vimentin,
      desmin and the neurofilament triplet protein NF-L aggregated into similar types
      of "unit-length filaments" (ULFs), whereas cytokeratins (CKs) 8/18 already
      yielded long IFs at this time point, so the ionic strength had to be reduced. The
      number of molecules per filament cross-section, as deduced from the MPL values,
      was lowest for CK8/18, i.e. 16 and 25 at two seconds compared to 16 and 21 at one
      hour. NF-L exhibited corresponding values of 26 and 30. Vimentin ULFs yielded a
      pronounced heterogeneity, with major peak values of 32 and 45 at two seconds and
      30, 37 and 44 after one hour. Desmin formed filaments of distinctly higher mass
      with 47 molecules per cross-section, at two seconds and after one hour of
      assembly. This indicates that individual types of IF proteins generate filaments
      with distinctly different numbers of molecules per cross-section. Also, the
      observed significant reduction of apparent filament diameter of ULFs compared to
      the corresponding mature IFs is the result of a "conservative" radial compaction
      type reorganization within the filament, as concluded from the fact that both the
      immature and mature filaments contain very similar numbers of subunits per cross
      section. Moreover, the MPL composition of filaments is strikingly dependent on
      the assembly conditions employed. For example, vimentin fibers formed in 0.7 mM
      phosphate (pH 7.5), 2.5 mM MgCl2, yield a significantly increased number of
      molecules per cross-section (56 and 84) compared to assembly under standard
      conditions. Temperature also strongly influences assembly: above a certain
      threshold temperature "pathological" ULFs form that are arrested in this state,
      indicating that the system is forced into strong but unproductive interactions
      between subunits. Similar "dead-end" structures were obtained with vimentins
      mutated to introduce principal alterations in subdomains presumed to be of
      general structural importance, indicating that these sequence changes led to new
      modes of intermolecular interactions.

PMID- 10064707
TI  - The Fab and Fc fragments of IgA1 exhibit a different arrangement from that in
      IgG: a study by X-ray and neutron solution scattering and homology modelling.
AB  - Human immunoglobulin A (IgA) is an abundant antibody that mediates immune
      protection at mucosal surfaces as well as in plasma. The IgA1 isotype contains
      two four-domain Fab fragments and a four-domain Fc fragment analogous to that in
      immunoglobulin G (IgG), linked by a glycosylated hinge region made up of 23 amino
      acid residues from each of the heavy chains. IgA1 also has two 18 residue
      tailpieces at the C terminus of each heavy chain in the Fc fragment. X-ray
      scattering using H2O buffers and neutron scattering using 100 % 2H2O buffers were
      performed on monomeric IgA1 and a recombinant IgA1 that lacks the tailpiece
      (PTerm455). The radii of gyration RG from Guinier analyses were similar at 6.11
      6.20 nm for IgA1 and 5.84-6.16 nm for PTerm455, and their cross-sectional radii
      of gyration RXS were also similar. The similarity of the RG and RXS values
      suggests that the tailpiece of IgA1 is not extended outwards in solution. The
      IgA1 RG values are higher than those for IgG, and the distance distribution
      function P(r) showed two distinct peaks, whereas a single peak was observed for
      IgG. Both results show that the hinge of IgA1 results in an extended Fab and Fc
      arrangement that is different from that in IgG. Automated curve-fit searches
      constrained by homology models for the Fab and Fc fragments were used to model
      the experimental IgA1 scattering curves. A translational search to optimise the
      relative arrangement of the Fab and Fc fragments held in a fixed orientation
      resembling that in IgG was not successful in fitting the scattering data. A new
      molecular dynamics curve-fit search method generated IgA1 hinge structures to
      which the Fab and Fc fragments could be connected in any orientation. A search
      based on these identified a limited family of IgA1 structures that gave good
      curve fits to the experimental data. These contained extended hinges of length
      about 7 nm that positioned the Fab-to-Fab centre-to-centre separation 17 nm apart
      while keeping the corresponding Fab-to-Fc separation at 9 nm. The resulting
      extended T-shaped IgA1 structures are distinct from IgG structures previously
      determined by scattering and crystallography which have Fab-to-Fab and Fab-to-Fc
      centre-to-centre separations of 7-9 nm and 6-8 nm, respectively. It was concluded
      that the IgA1 hinge is structurally distinct from that in IgG, and this results
      in a markedly different antibody structure that may account for a unique immune
      role of monomeric IgA1 in plasma and mucosa.

PMID- 10064708
TI  - Glycyl-tRNA synthetase uses a negatively charged pit for specific recognition and
      activation of glycine.
AB  - The crystal structures of glycyl-tRNA synthetase (GlyRS) from Thermus
      thermophilus, a homodimeric class II enzyme, were determined in the enzyme
      substrate and enzyme-product states corresponding to the first step of
      aminoacylation. GlyRS was cocrystallized with glycine and ATP, which were
      transformed by the enzyme into glycyl-adenylate and thus gave the enzyme-product
      complex. To trap the enzyme-substrate complex, the enzyme was combined with the
      glycine analog ethanolamine and ATP. The ligands are bound in fixed orientations
      in the substrate-binding pocket of the N-terminal active site domain, which
      contains the classical class II aminoacyl-tRNA synthetase (aaRS) fold. Since
      glycine does not possess a side-chain, much of the specificity of the enzyme is
      directed toward excluding any additional atoms beyond the alpha-carbon atom.
      Several carboxylate residues of GlyRS line the glycine binding pocket; two of
      them interact directly with the alpha-ammonium group. In addition, the enzyme
      utilizes the acidic character of the pro-L alpha-hydrogen atom by contacting it
      via a glutamate carboxylic oxygen atom. A guanidino eta-nitrogen atom of the
      class II aaRS-conserved motif 2 arginine interacts with the substrate carbonyl
      oxygen atom. These features serve to attract the small amino acid substrate into
      the active site and to position it in the correct orientation. GlyRS uses class
      II-conserved residues to interact with the ATP and the adenosine-phosphate moiety
      of glycyl-adenylate. On the basis of this similarity, we propose that GlyRS
      utilizes the same general mechanism as that employed by other class II aminoacyl
      tRNA synthetases.

PMID- 10064709
TI  - The stationary statistical properties of human coding sequences.
AB  - We introduce a generally applicable method for the discovery and quantitation of
      all of the characteristic statistical properties of a class of biological
      sequences, given examples from the class. This method employs a reversible binary
      encoding of sequences into the binary digits -1 and +1. Then, provided that the
      sample is sufficient, the sample cumulants on the subsets of digit positions will
      manifest all of the statistical properties of the class. As an illustration, we
      present the main results of a complete characterization of the stationary
      statistical properties of human coding sequences, in terms of their sample
      cumulants. Many of the telling sample cumulants are described.

PMID- 10064710
TI  - An irregular beta-bulge common to a group of bacterial RNases is an important
      determinant of stability and function in barnase.
AB  - Single amino acid residue substitutions rarely destroy the structural integrity
      of proteins. Substitution of glycine residues, however, is among the few sorts of
      alterations that can have such an effect. Here, we seek to understand what
      accounts for the extreme functional impairment of the bacterial ribonuclease
      barnase upon substitution of Gly52 or Gly53. We find that inactivation is caused
      by overall disruption of the folded state that manifests itself in three ways:
      (1) dramatically reduced stability (by 5.2 to 8.4 kcal mol-1 for mutants showing
      inactivation in vivo); (2) progressive loss of folded-state activity with
      increasing temperature, indicating a less well formed fold; and (3) substantial
      proteolytic degradation of mutant enzymes in vivo. Examination of two deletion
      mutants, missing either Gly53 or Asp54, shows that the irregular beta-bulge
      formed by these two residues is of vital importance to the structural integrity
      of barnase. The parallel behaviour of mutants carrying replacements of either of
      the two glycine residues therefore appears to arise from a common mechanism:
      disruption of local structure at the beta-bulge. The importance of this
      structural element to the function of barnase raises the question of whether it
      may be present in other RNases. The Streptomyces enzymes RNase Sa and RNase St
      differ considerably from barnase in both sequence and structure, yet both show
      significant sequence similarity to barnase over a region beginning at Gly53.
      Structural comparison indicates that the Streptomyces enzymes do have the barnase
      like irregular beta-bulge, making this an important characteristic feature of a
      group of bacterial ribonucleases. The sensitivity of this feature demonstrates
      that detailed aspects of local structure may have a major role in determining the
      overall structural and functional properties of an enzyme, even where no
      explanation for this role is readily apparent. If this is a general
      characteristic of the structure-function relationship, it may pose a formidable
      obstacle to the de novo design of new enzymes.

PMID- 10064711
TI  - Structural response to mutation at a protein-protein interface.
AB  - We have crystallised three mutants of the barnase-barstar complex in which
      interactions across the interface have been deleted by simultaneous mutation of
      both residues involved in the interaction. Each mutant deletes a different type
      of interaction at the interface: the first complex bnHis102-->Ala-bsTyr29-->Phe
      (bn, barnase; bs, barstar), deletes a van der Waals packing interaction; the
      second complex, bnLys27-->Ala-bsThr42-->Ala, deletes a hydrogen bond; the third,
      bnLys27-->Ala-bsAsp35-->Ala, deletes a long-range charge-charge interaction. The
      contribution of each of these side-chains to the stability of the complex is
      known; the coupling energy between the deleted side-chains is also known. Despite
      each of the double mutants being significantly destabilised compared with the
      wild-type, the effects of mutation are local. Only small movements in the main
      chain surrounding the sites of mutation and some larger movements of neighbouring
      side-chains are observed in the mutant complexes. The exact response to mutation
      is context-dependent and for the same mutant can vary depending upon the
      environment within the crystal. In some double mutant complexes, interfacial
      pockets, which are accessible to bulk solvent are formed, whereas interfacial
      cavities which are isolated from bulk solvent, are formed in others. In all
      double mutants, water molecules fill the created pockets and cavities. These
      water molecules mimic the deleted side-chains by occupying positions close to the
      non-carbon atoms of truncated side-chains and re-making many hydrogen bonds made
      by the truncated side-chains in the wild-type. It remains extremely difficult,
      however, to correlate energetic and structural responses to mutation because of
      unknown changes in entropy and entropy-enthalpy compensation.

PMID- 10064712
TI  - Sulphate ions observed in the 2.12 A structure of a new crystal form of S.
      cerevisiae phosphoglycerate mutase provide insights into understanding the
      catalytic mechanism.
AB  - The structure of a new crystal form of Saccharomyces cerevisiae phosphoglycerate
      mutase has been solved and refined to 2.12 A with working and free R-factors of
      19.7 and 22.9 %, respectively. Higher-resolution data and greater non
      crystallographic symmetry have produced a more accurate protein structure than
      previously. Prominent among the differences from the previous structure is the
      presence of two sulphate ions within each active site cleft. The separation of
      the sulphates suggests that they may occupy the same sites as phospho groups of
      the bisphosphate ligands of the enzyme. Plausible binding modes for 2,3
      bisphosphoglycerate and 1, 3-bisphosphoglycerate are thereby suggested. These
      results support previous conclusions from mutant studies, highlight interesting
      new targets for mutagenesis and suggest a possible mechanism of enzyme
      phosphorylation.

PMID- 10064713
TI  - Structure of D-allose binding protein from Escherichia coli bound to D-allose at
      1.8 A resolution.
AB  - ABC transport systems for import or export of nutrients and other substances
      across the cell membrane are widely distributed in nature. In most bacterial
      systems, a periplasmic component is the primary determinant of specificity of the
      transport complex as a whole. We report here the crystal structure of the
      periplasmic binding protein for the allose system (ALBP) from Escherichia coli,
      solved at 1.8 A resolution using the molecular replacement method. As in the
      other members of the family (especially the ribose binding protein, RBP, with
      which it shares 35 % sequence homology), this structure consists of two similar
      domains joined by a three-stranded hinge region. The protein is believed to exist
      in a dynamic equilibrium of closed and open conformations in solution which is an
      important part of its function. In the closed ligand-bound form observed here, D
      allose is buried at the domain interface. Only the beta-anomer of allopyranose is
      seen in the crystal structure, although the alpha-anomer can potentially bind
      with a similar affinity. Details of the ligand-binding cleft reveal the features
      that determine substrate specificity. Extensive hydrogen bonding as well as
      hydrophobic interactions are found to be important. Altogether ten residues from
      both the domains form 14 hydrogen bonds with the sugar. In addition, three
      aromatic rings, one from each domain with faces parallel to the plane of the
      sugar ring and a third perpendicular, make up a hydrophobic stacking surface for
      the ring hydrogen atoms. Our results indicate that the aromatic rings forming the
      sugar binding cleft can sterically block the binding of any hexose epimer except
      D-allose, 6-deoxy-allose or 3-deoxy-glucose; the latter two are expected to bind
      with reduced affinity, due to the loss of some hydrogen bonds. The pyranose form
      of the pentose, D-ribose, can also fit into the ALBP binding cleft, although with
      lower binding affinity. Thus, ALBP can function as a low affinity transporter for
      D-ribose. The significance of these results is discussed in the context of the
      function of allose and ribose transport systems.

PMID- 10064714
TI  - The domains of protein S from Myxococcus xanthus: structure, stability and
      interactions.
AB  - Protein S from Myxococcus xanthus is a member of the beta gamma-crystallin
      superfamily. Its N and C-terminal domains (NPS and CPS, respectively) show a high
      degree of structural similarity and possess the capacity to bind two calcium ions
      per domain. For NPS, their positions were determined by X-ray diffraction at 1.8
      A resolution, making use of molecular replacement with the NMR structure as
      search model. The overall topology of NPS is found to be practically the same as
      in complete protein S. In natural protein S, the domains fold independently, with
      a significant increase in stability and cooperativity of folding in the presence
      of Ca2+. The recombinant isolated domains are stable monomers which do not show
      any tendency to combine to "nicked" full-length protein S. In order to
      investigate the stability and folding of natural protein S and its isolated
      domains, spectroscopic techniques were applied, measuring the reversible urea and
      temperature-induced unfolding transitions at varying pH. The increment of Ca2+ to
      the free energy of stabilization amounts to -10 and -5 kJ/mol for NPS and CPS,
      respectively. For both NPS and CPS, in the absence and in the presence of 3 mM
      CaCl2, the two-state model is valid. Comparing DeltaGU-->N for CPS (-21 kJ/mol at
      pH 7, liganded with Ca2+) with its increment in the intact two-domain protein,
      the stability of the isolated domain turns out to be decreased in a pH-dependent
      manner. In contrast, the stability of Ca2+-loaded NPS (DeltaGU-->N=-31 kJ/mol, pH
      7) is nearly unchanged down to pH 2 where Ca2+ is released (DeltaGU-->N=-26
      kJ/mol, pH 2). In intact protein S, the N-terminal domain is destabilized
      relative to NPS. Evidently, apart from Ca2+ binding, well-defined domain
      interactions contribute significantly to the overall stability of intact protein
      S.

PMID- 10064715
TI  - Analysis of the relationship between enzyme activity and its internal motion
      using nuclear magnetic resonance: 15N relaxation studies of wild-type and mutant
      lysozyme.
AB  - A mutant lysozyme where R14 and H15 are deleted together has higher activity and
      a similar binding ability to an inhibitor, trimer of N-acetylglucosamine
      ((NAG)3), compared with wild-type lysozyme. Since this has been attributed to
      intrinsic protein dynamic properties, we investigated the relationship between
      the activity and the internal motions of proteins. Backbone dynamics of the free
      and the complex forms with the (NAG)3 have been studied by measurement of the 15N
      T1 and T2 relaxation rates and NOE determinations at 600 MHz. Analysis of the
      data using the model-free formalism showed that the generalized order parameters
      (S2) were almost the same in wild-type and mutant lysozyme in unbound state,
      indicating that the mutation had little effect on the global internal motions. On
      the other hand, in the presence of (NAG)3, although some signals located around
      the active site were broadened or decreased in intensity because of strong
      perturbation by (NAG)3, there were several residues that showed increased or
      decreased backbone S2 in the complexed lysozymes. A comparison of the internal
      motions of the wild-type and mutant complexes showed a number of distinct dynamic
      differences between them. In particular, many residues located at or near active
      site regions (turn 1, strand 2, turn 2 and long loop), displayed greater backbone
      dynamics reflecting the order parameter in mutant complex relative to mutant
      free. Furthermore, the Rex values at the loop C-D region, which was considered to
      be important for enzymatic activity, significantly increased. From these results,
      it was suggested that variations in the dynamics of these regions may play an
      important role in the enzyme activity.

PMID- 10064716
TI  - Side-chain conformational disorder in a molten globule: molecular dynamics
      simulations of the A-state of human alpha-lactalbumin.
AB  - Molten globules are compact, partially folded forms of proteins consisting of an
      ensemble of interconverting conformers with disorder in the side-chain packing
      across the ensemble. Using insights from experimental data a strategy has been
      devised to describe this side-chain disorder in a molten globule. Structures of
      human alpha-lactalbumin have been generated with significantly different side
      chain packings to those observed in the native protein by changing all the chi1
      torsion angles. Molecular dynamics simulations have been carried out starting
      from these structures using conditions under which the molten globule is seen
      experimentally, i.e. at low pH and in the absence of calcium. In each simulation,
      low energy conformers were generated which are compact and retain substantial
      secondary structure and an overall native fold, but have very different side
      chain contacts; there are all-atom root-mean-square differences of up to 0.5 nm
      between the different structures. The structures from the different simulations
      taken together provide an initial description of possible contributors to the
      ensemble of conformers in the molten globule state which is consistent, at least
      in general terms, with experimental data.

PMID- 10064717
TI  - Rapid folding with and without populated intermediates in the homologous four
      helix proteins Im7 and Im9.
AB  - The kinetics and thermodynamics of the folding of the homologous four-helix
      proteins Im7 and Im9 have been characterised at pH 7.0 and 10 degrees C. These
      proteins are 60 % identical in sequence and have the same three-dimensional
      structure, yet appear to fold by different kinetic mechanisms. The logarithm of
      the folding and unfolding rates of Im9 change linearly as a function of urea
      concentration and fit well to an equation describing a two-state mechanism (with
      a folding rate of 1500 s-1, an unfolding rate of 0. 01 s-1, and a highly compact
      transition state that has approximately 95 % of the native surface area buried).
      By contrast, there is clear evidence for the population of an intermediate during
      the refolding of Im7, as indicated by a change in the urea dependence of the
      folding rate and the presence of a significant burst phase amplitude in the
      refolding kinetics. Under stabilising conditions (0.25 M Na2SO4, pH 7.0 and 10
      degrees C) the folding of Im9 remains two-state, whilst under similar conditions
      (0.4 M Na2SO4, pH 7.0 and 10 degrees C) the intermediate populated during Im7
      refolding is significantly stabilised (KUI=125). Equilibrium denaturation
      experiments, under the conditions used in the kinetic measurements, show that Im7
      is significantly less stable than Im9 (DeltaDeltaG 9.3 kJ/mol) and the DeltaG and
      m values determined accord with those obtained from the fit to the kinetic data.
      The results show, therefore, that the population of an intermediate in the
      refolding of the immunity protein structure is defined by the precise amino acid
      sequence rather than the global stability of the protein. We discuss the
      possibility that the intermediate of Im7 is populated due to differences in helix
      propensity in Im7 and Im9 and the relevance of these data to the folding of
      helical proteins in general.

PMID- 10064718
TI  - Increased helix and protein stability through the introduction of a new tertiary
      hydrogen bond.
AB  - In an effort to quantify the importance of hydrogen bonding and alpha-helix
      formation to protein stability, a capping box motif was introduced into the small
      phosphocarrier protein HPr. Previous studies had confirmed that Ser46, at the N
      cap position of the short helix-B in HPr, serves as an N-cap in solution. Thus,
      only a single-site mutation was required to produce a canonical S-X-X-E capping
      box: Lys49 at the N3 position was substituted with a glutamic acid residue.
      Thermal and chemical denaturation studies on the resulting K49E HPr show that the
      designed variant is approximately 2 kcal mol-1 more stable than the wild-type
      protein. However, NMR studies indicate that the side-chain of Glu49 does not
      participate in the expected capping H-bond interaction, but instead forms a new
      tertiary H-bond that links helix-B to the four-stranded beta-sheet of HPr. Here,
      we demonstrate that a strategy in which new non-native H-bonds are introduced can
      generate proteins with increased stability. We discuss why the original capping
      box design failed, and compare the energetic consequences of the new tertiary
      side-chain to main-chain H-bond with a local (helix-capping) side-chain to main
      chain H-bond on the protein's global stability.

PMID- 10064719
TI  - The Greek key protein apo-pseudoazurin folds through an obligate on-pathway
      intermediate.
AB  - Folding of the 123 amino acid residue Greek key protein apo-pseudo azurin from
      Thiosphaera pantotropha has been examined using stopped-flow circular dichroism
      in 0.5 M Na2SO4 at pH 7.0 and 15 degrees C. The data show that the protein folds
      from the unfolded state with all eight proline residues in their native isomers
      (seven trans and one cis) to an intermediate within the dead-time of the stopped
      flow mixing (50 ms). The urea dependence of the rates of folding and unfolding of
      the protein were also determined. The ratio of the folding rate to the unfolding
      rate (extrapolated into water) is several orders of magnitude too small to
      account for the equilibrium stability of the protein, consistent with the
      population of an intermediate. Despite this, the logarithm of the rate of folding
      versus denaturant concentration is linear. These data can be rationalised by the
      population of an intermediate under all refolding conditions. Accordingly,
      kinetic and equilibrium measurements were combined to fit the chevron plot to an
      on-pathway model (U <==> I <==> N). The fit shows that apo-pseudoazurin rapidly
      forms a compact species that is stabilised by 25 kJ/mol before folding to the
      native state at a rate of 2 s-1. Although the data can also be fitted to an off
      pathway model (I <==> U <==> N), the resulting kinetic parameters indicate that
      the protein would have to fold to the native state at a rate of 86,000 s-1 (a
      time constant of only 12 microseconds). Similarly, models in which this
      intermediate is bypassed also lead to unreasonably fast refolding rates. Thus,
      the intermediate populated during the refolding of apo-pseudoazurin appears to be
      obligate and on the folding pathway. We suggest, based on this study and others,
      that some intermediates play a critical role in limiting the search to the native
      state.

PMID- 10064720
TI  - A natural grouping of motifs with an aspartate or asparagine residue forming two
      hydrogen bonds to residues ahead in sequence: their occurrence at alpha-helical N
      termini and in other situations.
AB  - Examination of the ways side-chain carboxylate and amide groups in high
      resolution protein crystal structures form hydrogen bonds with main-chain atoms
      reveals that the most common category is a two-hydrogen-bond four to five residue
      motif with an aspartate or asparagine (Asx) at the first residue, for which we
      propose the name Asx-motif. Similar motifs with glutamate or glutamine residues
      at that position are rare. Asx-motifs occur typically as (1) a common feature of
      the N termini of alpha-helices called the Asx N-cap motif; (2) an independent
      motif, usually a beta-turn with an appropriately hydrogen-bonded Asx as the first
      residue; and (3) a motif incorporated in a beta-bulge loop. Asx-motifs are
      common, there being just under two-and-a-half in an average-sized protein
      subunit; of these, about 55 % are Asx N-cap motifs. Because they occur often in
      many situations, it seems that these motifs have an inherent propensity to form
      on their own rather than just being a feature stabilised at the end of a helix.
      Asx-motifs also occur in functionally interesting situations in aspartyl
      proteases, citrate synthase, EF hands, haemoglobins, lipocalins, glutathione
      reductase and the alpha/beta hydrolases.

PMID- 10064721
TI  - A recurring two-hydrogen-bond motif incorporating a serine or threonine residue
      is found both at alpha-helical N termini and in other situations.
AB  - Side-chain hydroxyl residues in protein crystal structures often form hydrogen
      bonds with main-chain atoms. The most common bond arrangement is a four to five
      residue motif in which a serine or threonine is the first residue forming two
      characteristic hydrogen bonds to residues ahead of it in sequence. We call them
      ST-motifs, by analogy with the term Asx-motif we suggested for the related motifs
      with aspartate and asparagine residues. ST-motifs are common, there being just
      under one and a half in a typical protein subunit. Asx-motifs are even more
      common, such that 9 % of the residues of an average protein consist of Asx or ST
      motifs. Of the ST-motifs, three-quarters are at helical N termini, and the rest
      occur by themselves or in conjunction with beta-bulge loops. A third of all alpha
      helices have either ST-motifs or Asx-motifs at their N termini. Previous work has
      emphasised the occurrence of the capping box at alpha-helical N termini, but the
      capping box occurs in only 5 % of alpha-helical N termini; also, we point out
      that it can be regarded as a subset of the ST-motif (or, occasionally, of the Asx
      motif). By comparing related sequences, the rates which amino acid residues at
      the first position of ST or Asx-motifs interchange during evolution are examined.
      Serine <==> threonine, and aspartate <==> asparagine, interchange is rapid; inter
      pair exchange is slower, but much faster than exchange with other amino acid
      residues. This is consistent with the general similarity of ST-motifs and Asx
      motifs combined with some subtle structural differences between them that are
      described.

PMID- 10064722
TI  - The projection structure of the low temperature K intermediate of the
      bacteriorhodopsin photocycle determined by electron diffraction.
AB  - Bacteriorhodopsin (bR) is an integral membrane protein which absorbs visible
      light and pumps protons across the cell membrane of Halobacterium salinarium. bR
      is one of the few membrane-bound pumps whose structure is known at atomic
      resolution. Changes in the protein structure of bR are a crucial element in the
      mechanism of proton pumping and can be followed by a variety of spectroscopic,
      and diffraction methods. A number of intermediates in the photocycle have been
      identified spectroscopically and a number of laboratories have been successful in
      reporting the structural changes taking place in the later stages of the
      photocycle over the millisecond time-scale using diffraction techniques. These
      studies have revealed significant changes in the protein structure, possibly
      involving changes in flexibility and/or movement of helices. Earlier
      intermediates which arise and decay on the picosecond to microsecond time-scale
      have proven more difficult to trap. Here, we report for the first time the
      successful trapping and diffraction analysis of bR in a low temperature state
      resembling the very early intermediate, K. We have calculated a projection
      difference map to 3.5 A resolution. The map reveals no significant structural
      changes in the molecule, despite having a very low background noise level. This
      does not rule out the possibility of movements in a direction perpendicular to
      the plane of the membrane. However, the data are consistent with other evidence
      that significant structural changes do not occur in the protein itself.

PMID- 10064723
TI  - Three-dimensional structure analysis of PROSITE patterns.
AB  - Pattern matches for each of the sequence patterns in PROSITE, a database of
      sequence patterns, were searched in all protein sequences in the Brookhaven
      Protein Data Bank (PDB). The three-dimensional structures of the pattern matches
      for the 20 patterns with the largest numbers of hits were analysed. We found that
      the true positives have a common three-dimensional structure for each pattern;
      the structures of false positives, found for six of the 20 patterns, were clearly
      different from those of the true positives. The results suggest that the true
      pattern matches each have a characteristic common three-dimensional structure,
      which could be used to create a template to define a three-dimensional functional
      pattern.

PMID- 10064724
TI  - Transgenic rabbits as models for atherosclerosis research.
AB  - Several characteristics of the rabbit make it an excellent model for the study of
      lipoprotein metabolism and atherosclerosis. New Zealand White (NZW) rabbits have
      low plasma total cholesterol concentrations, high cholesteryl ester transfer
      protein activity, low hepatic lipase (HL) activity, and lack an analogue of human
      apolipoprotein (apo) A-II, providing a unique system in which to assess the
      effects of human transgenes on plasma lipoproteins and atherosclerosis
      susceptibility. Additionally, rabbit models of human lipoprotein disorders, such
      as the Watanabe Heritable Hyperlipidemic (WHHL) and St. Thomas' Hospital strains,
      models of familial hypercholesterolemia and familial combined hyperlipidemia,
      respectively, allow for the assessment of candidate genes for potential use in
      the treatment of dyslipoproteinemic patients. To date, transgenes for human
      apo(a), apoA-I, apoB, apoE2, apoE3, HL, and lecithin:cholesterol acyltransferase
      (LCAT), as well as for rabbit apolipoprotein B mRNA-editing enzyme catalytic poly
      peptide 1 (APOBEC-1), have been expressed in NZW rabbits, whereas only those for
      human apoA-I and LCAT have been introduced into the WHHL background. All of these
      transgenes have been shown to have significant effects on plasma lipoprotein
      concentrations. In both NZW and WHHL rabbits, human apoA-I expression was
      associated with a significant reduction in the extent of aortic atherosclerosis,
      which was similarly the case for LCAT in rabbits having at least one functional
      LDL receptor allele. Conversely, expression of apoE2 in NZW rabbits caused
      increased susceptibility to atherosclerosis. These studies provide new insights
      into the mechanisms responsible for the development of atherosclerosis,
      emphasizing the strength of the rabbit model in cardiovascular disease research.

PMID- 10064725
TI  - Transcription factors CCAAT/enhancer-binding protein beta and nuclear factor-Y
      bind to discrete regulatory elements in the very low density lipoprotein receptor
      promoter.
AB  - Expression of the very low density lipoprotein receptor (VLDL-R) is barely
      detectable in liver, but occurs in adipose tissue, skeletal muscle, heart, and
      placenta, where it is postulated to supply triglyceride to tissues that utilize
      fatty acids. To investigate its tissue-specific expression, cell lines were
      transfected with luciferase reporter gene constructs driven by the 5'-flanking
      region of the VLDL-R gene. Transcriptional activity of a 4.2-kb promoter fragment
      was 5-fold higher in BeWo placental cells than in Huh-7 hepatoma cells,
      consistent with relative endogenous expression of the VLDL-R. By deletion
      analysis, DNase I protection assays and site-directed mutagenesis, two regulatory
      elements were essential for maximal promoter activity in BeWo cells: footprint
      site D (-856 to -830) and an inverted CCAAT box (-703 to -707). Mutation of
      either element reduced promoter activity by 60% in BeWo cells, but had little
      effect in Huh-7 cells, suggesting that these elements direct cell-type specific
      transcription. Electrophoretic mobility-shift assays with BeWo nuclear extracts
      revealed that the inverted CCAAT box binds transcription factor NF-Y, and site D
      binds CCAAT/enhancer-binding protein b (C/EBPbeta) and minor amounts of
      C/EBPalpha and C/EBPdelta. Overexpression of a dominant negative NF-YA vector
      confirmed involvement of NF-Y in the regulation of the VLDL-receptor gene through
      the CCAAT box. However overexpression of C/EBP could not stimulate transcription
      from the VLDL-receptor promoter nor from site D fused to a heterologous promoter,
      suggesting that the simultaneous binding of an accessory factor(s) may be
      necessary for C/EBP transactivation via the D site.

PMID- 10064726
TI  - 17beta-estradiol reduces tumor necrosis factor-alpha-mediated LDL accumulation in
      the artery wall.
AB  - Estrogens have direct effects on the vascular wall that may prevent the
      development of atherosclerosis. In particular, estrogens, such as 17beta
      estradiol (estradiol), are known to have potent antioxidant activity. Tumor
      necrosis factor-alpha (TNF) is found in human atheroma and produces oxygen
      derived free radicals. These oxygen-derived free radicals may modify low density
      lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does
      TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated
      increase in LDL accumulation be prevented by the antioxidant activity of
      estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and
      perfused with fluorescently labeled LDL and arterial LDL flux was measured using
      quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml)
      to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation
      (1.50 +/- 0.37 ng/min per cm2 vs. 3.38 +/- 0.48 ng/min per cm2; P < 0.01).
      Estradiol (65 pg/ml) and alpha-tocopherol (6 mg/L) both attenuated TNF-mediated
      LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL
      accumulation through cellular production of oxygen-derived free radicals. These
      results support an antioxidant role for estradiol in the protection against LDL
      accumulation in the artery wall and subsequent progression of atherosclerosis.

PMID- 10064727
TI  - Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression
      in macrophages.
AB  - Foam cells formed from receptor-mediated uptake of lipoprotein cholesterol by
      macrophages in the arterial intima are critical in the initiation, progression,
      and stability of atherosclerotic lesions. Macrophages accumulate cholesterol when
      conditions favor esterification by acyl-CoA:cholesterol acyltransferase (ACAT)
      over cholesteryl-ester hydrolysis by a neutral cholesteryl-ester hydrolase, such
      as hormone-sensitive lipase (HSL), and subsequent cholesterol efflux mediated by
      extracellular acceptors. We recently made stable transfectants of a murine
      macrophage cell line, RAW 264.7, that overexpressed a rat HSL cDNA and had a 5
      fold higher rate of cholesteryl-ester hydrolysis than control cells. The current
      study examined the effect of macrophage-specific HSL overexpression on
      susceptibility to diet-induced atherosclerosis in mice. A transgenic line
      overexpressing the rat HSL cDNA regulated with a macrophage-specific scavenger
      receptor promoter-enhancer was established by breeding with C57BL/6J mice.
      Transgenic peritoneal macrophages exhibited macrophage-specific 7-fold
      overexpression of HSL cholesterol esterase activity. Total plasma cholesterol
      levels in transgenic mice fed a chow diet were modestly elevated 16% compared to
      control littermates. After 14 weeks on a high-fat, high-cholesterol diet, total
      cholesterol increased 3-fold, with no difference between transgenics and
      controls. However, HSL overexpression resulted in thicker aortic fatty lesions
      that were 2.5-times larger in transgenic mice. HSL expression in the aortic
      lesions was shown by immunocytochemistry. Atherosclerosis was more advanced in
      transgenic mice exhibiting raised lesions involving the aortic wall, along with
      lipid accumulation in coronary arteries occurring only in transgenics. Thus,
      increasing cholesteryl-ester hydrolysis, without concomitantly decreasing ACAT
      activity or increasing cholesterol efflux, is not sufficient to protect against
      atherosclerosis. hormone-sensitive lipase overexpression in macrophages.

PMID- 10064728
TI  - Cholesteryl ester hydrolysis in J774 macrophages occurs in the cytoplasm and
      lysosomes.
AB  - The relationship of cholesteryl ester hydrolysis to the physical state of the
      cholesteryl ester in J774 murine macrophages was explored in cells induced to
      store cholesteryl esters either in anisotropic (ordered) inclusions or isotropic
      (liquid) inclusions. In contrast to other cell systems, the rate of cholesteryl
      ester hydrolysis was faster in cells containing anisotropic inclusions than in
      cells containing isotropic inclusions. Two contributing factors were identified.
      Kinetic analyses of the rates of hydrolysis are consistent with a substrate
      competition by co-deposited triglyceride in cells with isotropic inclusions. In
      addition, hydrolysis of cholesteryl esters in cells with anisotropic droplets is
      mediated by both cytoplasmic and lysosomal lipolytic enzymes, as shown by using
      the lysosomotropic agent, chloroquine, and an inhibitor of neutral cholesteryl
      ester hydrolase, umbelliferyl diethylphosphate. In cells containing anisotropic
      inclusions, hydrolysis was partially inhibited by incubation in media containing
      either chloroquine or umbelliferyl diethylphosphate. Together, chloroquine and
      umbelliferyl diethylphosphate completely inhibited hydrolysis. However, when
      cells containing isotropic inclusions were incubated with umbelliferyl
      diethylphosphate, cholesteryl ester hydrolysis was completely inhibited, but
      chloroquine had no effect. Transmission electron microscopy demonstrated a
      primarily lysosomal location for lipid droplets in cells with anisotropic
      droplets and both non-lysosomal and lysosomal populations of lipid droplets in
      cells with isotropic droplets. These results support the conclusion that there is
      a lysosomal component to the hydrolysis of stored cholesteryl esters in foam
      cells.

PMID- 10064729
TI  - No pathophysiologic relationship of soluble biliary proteins to cholesterol
      crystallization in human bile.
AB  - This study explores the pathophysiologic effects of soluble biliary glycoproteins
      in comparison to mucin gel and cholesterol content on microscopic crystal and
      liquid crystal detection times as well as crystallization sequences in lithogenic
      human biles incubated at 37 degrees C. Gallbladder biles from 13 cholesterol
      gallstone patients were ultracentrifuged and microfiltered (samples I). Total
      biliary lipids were extracted from portions of samples I, and reconstituted with
      0.15 m NaCl (pH 7.0) (samples II). Portions of samples II were supplemented with
      purified concanavalin A-binding biliary glycoproteins (final concentration = 1
      mg/mL) (samples III), or mucin gel (samples IV), respectively, isolated from the
      same cholesterol gallstone biles. Samples V consisted of extracted biliary lipids
      from uncentrifuged and unfiltered bile samples reconstituted with 0.15 m NaCl (pH
      7.0). Analytic lipid compositions of samples I through IV were identical for
      individual biles but, as anticipated, samples V displayed significantly higher
      cholesterol saturation indexes. Detection times of cholesterol crystals and
      liquid crystals were accelerated in the rank order of samples: IV > V > I = II =
      III, indicating that total soluble biliary glycoproteins in pathophysiologic
      concentration had no appreciable effect. Crystallization sequences (D. Q-H. Wang
      and M. C. Carey. J. Lipid Res. 1996. 37: 606-630; and 2539-2549) were similar
      among samples I through V. Crystal detection times and numbers of solid
      cholesterol crystals were accelerated in proportion to added mucin gel and the
      cholesterol saturation of bile only. For pathophysiologically relevant
      conditions, our results clarify that mucin gel and cholesterol content, but not
      soluble biliary glycoproteins, promote cholesterol crystallization in human
      gallbladder bile.

PMID- 10064730
TI  - Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial
      combined hyperlipidemia.
AB  - There is growing evidence of the capacity of vitamin A to regulate the expression
      of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV.
      This region in turn has been proposed to modulate the expression of
      hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined
      hyperlipidemia (FCHL). The hypothesis tested here was whether vitamin A
      (retinol), by controlling the expression of the AI-CIII-AIV gene cluster, plays a
      role in modulating the hyperlipidemic phenotype in FCHL. We approached the
      subject by studying three genetic variants of this region: a C1100-T transition
      in exon 3 of the apoC-III gene, a G3206-T transversion in exon 4 of the apoC-III
      gene, and a G-75-A substitution in the promoter region of the apoA-I gene. The
      association between plasma vitamin A concentrations and differences in the plasma
      concentrations of apolipoproteins A-I and C-III based on the different genotypes
      was assessed in 48 FCHL patients and 74 of their normolipidemic relatives. The
      results indicated that the subjects carrying genetic variants associated with
      increased concentrations of apoA-I and C-III (C1100-T and G-75-A) also presented
      increased plasma concentrations of vitamin A. This was only observed among the
      FCHL patients, which suggested that certain characteristics of these patients
      contributed to this association. The G3206-T was not associated with changes in
      either apolipoprotein concentrations or in vitamin A. In summary, we report a
      relationship between genetically determined elevations of proteins of the AI-CIII
      AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to
      confirm that vitamin A plays a role in FCHL which might also be important for its
      potential application to therapeutical approaches.

PMID- 10064731
TI  - Elevated hepatic lipase activity and low levels of high density lipoprotein in a
      normotriglyceridemic, nonobese Turkish population.
AB  - Low levels of high density lipoprotein cholesterol (HDL-C) are associated with
      increased risk of coronary heart disease and, in the United States, are often
      associated with hypertriglyceridemia and obesity. In Turkey, low HDL-C levels are
      highly prevalent, 53% of men and 26% of women having HDL-C levels <35 mg/dl, in
      the absence of hypertriglyceridemia and obesity. In this study to investigate the
      cause of low HDL-C levels in Turks, various factors affecting HDL metabolism were
      assessed in normotriglyceridemic Turkish men and women living in Istanbul and in
      non-Turkish men and women living in San Francisco. Turkish men and women had
      significantly lower HDL-C levels than the San Francisco men and women, as well as
      markedly lower apolipoprotein A-I levels (25 and 39 mg/dl lower, respectively).
      In both Turkish and non-Turkish subjects, the mean body mass index was <27 kg/m2,
      the mean triglyceride level was <120 mg/dl, and the mean total cholesterol was
      170-180 mg/dl. The mean hepatic triglyceride lipase activity was 21% and 31%
      higher in Turkish men and women, respectively, than in non-Turkish men and women,
      and remained higher even after subjects with a body mass index >50th percentile
      for men and women in the United States were excluded from the analysis. As no
      dietary or behavioral factors have been identified in the Turkish population that
      account for increased hepatic triglyceride lipase activity, the elevation most
      likely has a genetic basis. high density lipoprotein in a normotriglyceridemic,
      nonobese Turkish population.

PMID- 10064732
TI  - Characterization of a leukotriene C4 export mechanism in human platelets:
      possible involvement of multidrug resistance-associated protein 1.
AB  - Platelets express leukotriene (LT) C4 synthase and can thus participate in the
      formation of bioactive LTC4. To further elucidate the relevance of this
      capability, we have now determined the capacity of human platelets to export
      LTC4. Endogenously formed LTC4 was efficiently released from human platelets
      after incubation with LTA4 at 37 degrees C, whereas only 15% of produced LTC4 was
      exported when the cells were incubated at 0 degrees C. The activation energy of
      the process was calculated to 49.9 +/- 7.7 kJ/mol, indicating carrier-mediated
      LTC4 export. This was also supported by the finding that the transport was
      saturable, reaching a maximal export rate of 470 +/- 147 pmol LTC4/min x 10(9)
      platelets. Furthermore, markedly suppressed LTC4 transport was induced by a
      combination of the metabolic inhibitors antimycin A and 2-deoxyglucose,
      suggesting energy-dependent export. The presence in platelets of multidrug
      resistance-associated protein 1 (MRP1), a protein described to be an energy
      dependent LTC4 transporter in various cell types, was demonstrated at the mRNA
      and protein level. Additional support for a role of MRP1 in platelet LTC4 export
      was obtained by the findings that the process was inhibited by probenecid and the
      5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886. The present findings
      further support the physiological relevance of platelet LTC4 production.

PMID- 10064733
TI  - Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated
      endocytosis.
AB  - The genetic polymorphism of apolipoprotein E (apoE) is associated with the age of
      onset and relative risk of Alzheimer's disease (AD). In contrast to apoE3, the
      wild type allele, apoE4 confers an increased risk of late-onset AD. We
      demonstrate that the beta-amyloid peptide isoforms Abeta (1-28), Abeta (1-40),
      and Abeta (1-43) compete for the cellular metabolism of apoE3 and apoE4
      containing beta-very low density lipoproteins. An antibody raised against Abeta
      (1-28) cross-reacted with recombinant apoE. Epitope mapping revealed positive
      amino acid clusters as common epitopes of Abeta (13 through 17; HHQKL) and apoE
      (residues 144 through 148; LRKRL), both regions known to be heparin binding
      domains. Abeta in which amino acids 13 through 17 (HHQKL) were replaced by
      glycine (GGQGL) failed to compete with the cellular uptake of apoE enriched
      betaVLDL. These observations indicate that Abeta and apoE are taken up into cells
      by a common pathway involving heparan sulfate proteoglycans.

PMID- 10064734
TI  - Oxidized derivatives of 7-dehydrocholesterol induce growth retardation in
      cultured rat embryos: a model for antenatal growth retardation in the Smith-Lemli
      Opitz syndrome.
AB  - 7-Dehydrocholesterol accumulates in fetuses affected by the Smith-Lemli-Opitz
      syndrome as a result of a deficit in the ultimate step of cholesterol synthesis
      catalyzed by Delta7 reductase. Rat embryos explanted at gestation day 10 and
      cultured for 48 h in the presence of the Delta7 reductase inhibitor AY 9944 were
      used as a model to discriminate between the beneficial effect of supplementation
      with cholesterol and the deleterious effect of supplementation with 7
      dehydrocholesterol. Cholesterol supplementation in the form of mixed
      cholesterol/lecithin liposomes added to serum serving as the culture medium
      restores the growth of embryos which is markedly decreased in the presence of the
      inhibitor. 7-Dehydrocholesterol under identical conditions does not restore
      growth and impairs the beneficial effect of cholesterol added simultaneously. UV
      photooxidation of 7-dehydrocholesterol-supplemented culture medium enhances its
      embryotoxicity, which suggests uptake by the embryo of toxic by-products formed
      from 7-dehydrocholesterol. By contrast photooxidation of cholesterol-supplemented
      culture medium does not induce embryotoxicity. alpha-Tocopherol reduces the
      toxicity of photooxidized 7-dehydrocholesterol supplementing the culture medium.
      We conclude that 7-dehydrocholesterol does not fulfill the cholesterol
      requirement of the developing embryos and exerts an additional embryotoxic effect
      probably via oxidized by-products. This could explain the antenatal growth
      retardation of SLOS by a blockage of the maternal compensatory cholesterol
      influx.

PMID- 10064735
TI  - Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits:
      evidence for a non-stoichiometric, intestinal mechanism of action.
AB  - The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally
      similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological
      profiles of the saponins were virtually identical: both dose-dependently
      decreased the intestinal absorption of labeled cholesterol 25-75%, increased
      fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol
      content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg)
      completely prevented hypercholesterolemia. Decreases in plasma and hepatic
      cholesterol levels were strongly correlated with increased neutral sterol
      excretion. Ratios of neutral sterol excreted to pamaqueside administered were
      greater than 1:1 at all doses, in opposition to the formation of a stoichiometric
      complex previously suggested for tiqueside and other saponins. Ratios in
      tiqueside-treated rabbits were less than unity, a reflection of its lower
      potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma
      cholesterol concentrations than control animals fed a cholesterol-free diet,
      indicating that the compound also inhibited the absorption of biliary
      cholesterol. Intravenous administration of pamaqueside had no effect on plasma
      cholesterol levels despite plasma levels twice those observed in rabbits given
      pamaqueside orally. These data indicate that pamaqueside and tiqueside induce
      hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism
      that apparently differs from the stoichiometric complexation of cholesterol
      hypothesized for other saponins.

PMID- 10064736
TI  - Identification of a novel Arg-->Cys mutation in the LDL receptor that contributes
      to spontaneous hypercholesterolemia in pigs.
AB  - We previously carried out genetic and metabolic studies in a partially inbred
      herd of pigs carrying cholesterol-elevating mutations. Quantitative pedigree
      analysis indicated that apolipoprotein (apo)B and a second major gene were
      responsible for the hypercholesterolemia in these animals. In this study, we
      assessed LDL receptor function by three different methods: ligand blots of liver
      membranes using beta-very low density lipoprotein (VLDL) as a ligand; low density
      lipoprotein (LDL)-dependent proliferation of T-lymphocytes; and direct binding of
      125I-labeled LDL to cultured skin fibroblasts. All three methods demonstrated
      that LDL receptor ligands bound with decreased affinity to the LDL receptor in
      these animals. In skin fibroblasts from the hypercholesterolemic pigs, the Kd of
      binding was about 4-fold higher than in cells from normal pigs. The cDNA of the
      pig LDL receptor from normal and hypercholesterolemic pigs was isolated and
      sequenced. We identified a missense mutation that results in an Arg'Cys
      substitution at the position corresponding to Arg94 of the human LDL receptor.
      The mutation is in the third repeat of the ligand binding domain of the receptor.
      By single-stranded conformational polymorphism (SSCP) analysis, we studied the
      relationship between LDL receptor genotype and plasma cholesterol phenotype. In
      contrast to humans, the hypercholesterolemia associated with the LDL receptor
      mutation in pigs was expressed as a recessive trait. The LDL receptor mutation
      made a far more significant contribution to hypercholesterolemia than did the
      apoB mutation, consistent with observations made in human subjects with apoB
      mutations. Within each genotypic group (mutated apoB or mutated receptor), there
      was a wide range in plasma cholesterol. As the animals were on a well-controlled
      low-fat diet, this suggests that there are additional genetic factors that
      influence the penetrance of cholesterol-elevating mutations.

PMID- 10064737
TI  - Multiple dysfunctions of two apolipoprotein A-I variants, apoA-I(R160L)Oslo and
      apoA-I(P165R), that are associated with hypoalphalipoproteinemia in heterozygous
      carriers.
AB  - ApoA-I(R160L)Oslo and apoA-I(P165R) are naturally occurring apolipoprotein (apo)
      A-I variants that are associated with low HDL-cholesterol in heterozygous
      carriers. We characterized the capacity of these variants to bind lipid, to
      activate lecithin:cholesterol acyltransferase (LCAT), and to promote efflux of
      biosynthetic cholesterol from porcine aortic smooth muscle cells (SMCs) or
      exogenous cholesterol from lipid-loaded mouse peritoneal macrophages. During
      cholate dialysis, normal apoA-I and both variants associated completely with
      dipalmitoylphosphatidylcholine (DPPC) and formed rLpA-I of identical size.
      However, both apoA-I(P165R) and apoA-I(R160L)Oslo showed a reduced capacity to
      clear a turbid emulsion of dimyristoylphosphatidylcholine (DMPC). Compared to
      normal apoA-I, the LCAT-cofactor activity of apoA-I(P165R) and apoA-I(R160L)Oslo
      as defined by the ratio of Vmax to appKm was reduced significantly by 62% and
      29%, respectively (here and throughout the text, the apparent Km is given as
      Michaelis-Menten kinetics do not take particle binding into account and therefore
      would result in errors with an interfacial enzyme such as LCAT; Vmax estimates
      are not affected by this error). ApoA-I/DPPC complexes induced biphasic
      cholesterol efflux from SMCs with a fast and a slow efflux component. Compared to
      rLpA-I reconstituted with wild type apoA-I, rLpA-I with apoA-I(P165R) or apoA
      I(R160L)Oslo were significantly less effective in promoting cholesterol efflux
      from SMCs in incubations of 10 min duration but equally effective in incubations
      of 6 h duration. Lipid-free apoA-I did not induce efflux of biosynthetic
      cholesterol from SMCs but induced hydrolysis of cholesteryl esters and
      cholesterol efflux from acetyl-LDL-loaded mouse peritoneal macrophages. In the
      lipid-free form, both apoA-I variants promoted normal cholesterol efflux from
      murine peritoneal macrophages. We conclude that amino acid residues arginine 160
      and proline 165 of apoA-I contribute to the formation of a domain that is very
      important for initial lipid binding and contributes to LCAT-activation and
      promotion of initial cholesterol efflux but not to the stabilization of preformed
      rLpA-I.

PMID- 10064738
TI  - Plasmalogen status influences docosahexaenoic acid levels in a macrophage cell
      line. Insights using ether lipid-deficient variants.
AB  - Previously, this laboratory reported the isolation of variants, RAW. 12 and
      RAW.108, from the macrophage-like cell line RAW 264.7 that are defective in
      plasmalogen biosynthesis [Zoeller, R.A. et al. 1992. J. Biol. Chem. 267: 8299
      8306]. Fatty acid analysis showed significant changes in the mutants in the
      ethanolamine phospholipids (PE), the only phospholipid class in which the
      plasmalogen species, plasmenylethanolamine, contributes significantly. Within the
      PE fraction, docosapentaenoic (DPA; 22:5n-3) and docosahexaenoic (DHA; 22:6n-3)
      acids were reduced by approximately 50% in the variants while the levels of
      arachidonic acid (AA; 20:4n-6) remained unaffected. The decrease in DHA was
      accompanied by a 50% decrease in labeling PE with [3H]DHA over a 90-min period.
      Restoration of plasmenylethanolamine by supplementing the growth medium with sn 
      1-hexadecylglycerol (HG) completely reversed these changes in RAW. 108. Pre
      existing pools of plasmenylethanolamine were not required for restoration of
      normal [3H]DHA labeling; addition of HG only during the labeling period was
      sufficient. Due to the loss of Delta1'-desaturase in RAW.12, HG supplementation
      resulted in the accumulation of plasmenylethanolamine's immediate biosynthetic
      precursor, plasmanylethanolamine. Even though this latter phospholipid contained
      only the ether functionality (lacking the vinyl ether double bond) it was
      sufficient to restore wild type-like fatty acid composition and DHA labeling of
      the ethanolamine phospholipids, identifying the ether bond as a structural
      determinant for this specificity. In summary, we have used these mutants to
      establish that the plasmalogen status of a cell can influence the levels of
      certain polyunsaturated fatty acids. These results support the notion that
      certain polyunsaturated fatty acids, such as DHA, can be selectively targeted to
      plasmalogens and that this targeting occurs during de novo biosynthesis, or
      shortly thereafter, through modification of nascent plasmalogen pools.

PMID- 10064739
TI  - Dietary fish oils inhibit early events in the assembly of very low density
      lipoproteins and target apoB for degradation within the rough endoplasmic
      reticulum of hamster hepatocytes.
AB  - Dietary fish oils inhibited secretion and stimulated intracellular degradation of
      apolipoprotein (apo)B in hamster hepatocytes, while dietary sunflower oils
      stimulated secretion and had no effect on degradation of apoB. To investigate the
      intracellular site at which fish oils act, we have made use of our previous
      observations that inhibition of degradation by N-acetyl-leucyl-leucyl-norleucinal
      (ALLN) results in accumulation of apoB in the trans -Golgi membrane and does not
      stimulate secretion, while inhibition of degradation by o-phenanthroline results
      in accumulation of apoB in the rough endoplasmic reticulum membrane and
      stimulates secretion. Thus, ALLN protects apoB which has been diverted from
      secretion and o -phenanthroline protects apoB which is targetted for secretion.
      Addition of o -phenantholine to the incubation medium of hepatocytes from fish
      oil-fed hamsters inhibited degradation of apoB and stimulated its secretion in
      particles of the density of VLDL, while addition of ALLN had no effect. These
      observations suggest that dietary fish oils reversibly inhibit early steps in the
      assembly of very low density lipoprotein precursors and target apoB for
      degradation in the rough endoplasmic reticulum.

PMID- 10064740
TI  - Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post
      decapitative ischemia: a 31p NMR study.
AB  - Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been used to
      study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post
      decapitative ischemia. Lipids were extracted from rat brain homogenates and the
      extracts were thoroughly washed with aq. potassium ethylenediaminetetraacetic
      acid (EDTA). The lower organic phases were isolated and evaporated to dryness
      under a stream of nitrogen and the lipids were redissolved in CDCl3-CH3OH-H2O
      100.0:29.9:5.2 (v/v/v) for NMR analysis. Increasing the period of post
      decapitative ischemia resulted in an accumulation of two signals in the NMR
      spectra at 0.18 and 0.22 ppm (relative to the chemical shift of 1,2-diacyl-sn
      glycero-3-phosphocholine (PCDIACYL) at -0.84 ppm). These signals were identified
      as originating from 1,2-diacyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine
      (NAPEDIACYL) and 1-(1'-alkenyl)-2-acyl-sn -glycero-3-phospho-(N-acyl)
      ethanolamine (NAPEPLAS), respectively, by spiking with authentic materials.
      Additionally, the identification was verified by thin-layer chromatography, which
      also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K
      EDTA instead of the commonly used Cs-EDTA in the preparation of the NMR samples
      allowed the separation of the chemical shifts of N-acyl-ethanolamine
      phospholipids from those of the ethanolamine phospholipids. Moreover, the
      chemical shift of cardiolipin was moved from 0.15 ppm observed with Cs-EDTA to
      about 0.31 ppm with K-EDTA. The present study demonstrates that it is possible to
      detect and quantify post-decapitative accumulation of NAPE subclasses (NAPEDIACYL
      and NAPEPLAS) in rat brains by the use of 31P NMR spectroscopy.

PMID- 10064741
TI  - Apolipoprotein A-I charge and conformation regulate the clearance of
      reconstituted high density lipoprotein in vivo.
AB  - While low apolipoprotein A-I (apoA-I) levels are primarily associated with
      increased high density lipoprotein (HDL) fractional catabolic rate (FCR), the
      factors that regulate the clearance of HDL from the plasma are unclear. In this
      study, the effect of lipid composition of reconstituted HDL particles (LpA-I) on
      their rate of clearance from rabbit plasma has been investigated. Sonicated LpA-I
      containing 1 to 2 molecules of purified human apoA-I and 5 to 120 molecules of
      palmitoyl-oleoyl phosphatidylcholine (POPC) exhibit similar charge and plasma FCR
      to that for lipid free apoA-I, 2.8 pools/day. Inclusion of 1 molecule of apoA-II
      to an LpA-I complex increases the FCR to 3.5 pools/day, a value similar to that
      observed for exchanged-labeled HDL3. In contrast, addition of 40 molecules of
      triglyceride, diglyceride, or cholesteryl ester to a sonicated LpA-I containing
      120 moles of POPC and 2 molecules of apoA-I increases the negative charge of the
      particle and reduces the FCR to 1.8 pools/day. Discoidal LpA-I are the most
      positively charged lipoprotein particles and also have the fastest clearance
      rates, 4.5 pools/day. Immunochemical characterization of the different LpA-I
      particles shows that the exposure of an epitope at residues 98 to 121 of the apoA
      I molecule is associated with an increased negative particle charge and a slower
      clearance from the plasma. We conclude that the charge and conformation of apoA-I
      are sensitive to the lipid composition of LpA-I and play a central role in
      regulating the clearance of these lipoproteins from plasma. conformation regulate
      the clearance of reconstituted high density lipoprotein in vivo.

PMID- 10064742
TI  - Enrichment of canalicular membrane with cholesterol and sphingomyelin prevents
      bile salt-induced hepatic damage.
AB  - These studies were undertaken to characterize the role of plasma membrane
      cholesterol in canalicular secretory functions and hepatocyte integrity against
      intravenous taurocholate administration. Cholesterol and sphingomyelin
      concentrations and cholesterol/phospholipid ratios were significantly increased
      in canalicular membranes of diosgenin-fed rats, suggesting a more resistant
      structure against solubilization by taurocholate. During taurocholate infusion,
      control rats had significantly decreased bile flow, whereas diosgenin-fed animals
      maintained bile flow. Maximal cholesterol output increased by 176% in diosgenin
      fed rats, suggesting an increased precursor pool of biliary cholesterol in these
      animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats,
      whereas bile salt output remained at control levels. The kinetics of glutamic
      oxalacetic transaminase, lactic dehydrogenase, and alkaline phosphatase
      activities in bile showed a significantly faster release in control than in
      diosgenin-fed rats. After 30 min of intravenous taurocholate infusion, necrotic
      hepatocytes were significantly increased in control animals. Preservation of bile
      secretory functions and hepatocellular cytoprotection by diosgenin against the
      intravenous infusion of toxic doses of taurocholate was associated with an
      increased concentration of cholesterol and sphingomyelin in the canalicular
      membrane. The increase of biliary cholesterol output induced by diosgenin was
      correlated to the enhanced concentration of cholesterol in the canalicular
      membrane.

PMID- 10064743
TI  - Mass spectral study of polymorphism of the apolipoproteins of very low density
      lipoprotein.
AB  - New isoforms of apolipoprotein (apo)C-I and apoC-III have been detected in
      delipidated fractions from very low density lipoprotein (VLDL) using matrix
      assisted laser desorption (MALDI) and electrospray ionization (ESI) mass
      spectrometry (MS). The cleavage sites of truncated apoC-III isoforms have also
      been identified. The VLDL fractions were isolated by fixed-angle single-spin
      ultracentrifugation using a self-generating sucrose density gradient and
      delipidated using a newly developed C18 solid phase extraction protocol. Fifteen
      apoC isoforms and apoE were identified in the MALDI spectra and the existence of
      the more abundant species was verified by ESI-MS. The relative intensities of the
      apoCs are closely correlated in three normolipidemic subjects. A fourth subject
      with type V hyperlipidemia exhibited an elevated apoC-III level and a suppressed
      level of the newly discovered truncated apoC-I isoform. ApoC-II was found to be
      particularly sensitive to in vitro oxidation. The dynamic range and specificity
      of the MALDI assay shows that the complete apoC isoform profile and apoE
      phenotype can be obtained in a single measurement from the delipidated VLDL
      fraction.

PMID- 10064744
TI  - Calcium and cAMP are second messengers in the adipokinetic hormone-induced
      lipolysis of triacylglycerols in Manduca sexta fat body.
AB  - We have previously shown that stereospecific hydrolysis of stored triacylglycerol
      by a phosphorylatable triacylglycerol-lipase is the pathway for the adipokinetic
      hormone-stimulated synthesis of sn -1, 2-diacylglycerol in insect fat body. The
      current series of experiments were designed to determine whether cAMP and/or
      calcium are involved in the signal transduction pathway for adipokinetic hormone
      in the fat body. After adipokinetic hormone treatment, cAMP-dependent protein
      kinase activity in the fat body rapidly increased and reached a maximum after 20
      min, suggesting that adipokinetic hormone causes an increase in cAMP. Forskolin
      (0.1 micrometer), an adenylate cyclase activator, induced up to a 97% increase in
      the secretion of diacylglycerol from the fat body. 8Br-cAMP (a membrane-permeable
      analog of cAMP) produced a 40% increase in the hemolymph diacylglycerol content.
      Treatment with cholera toxin, which also stimulates adenylate cyclase, induced up
      to a 145% increase in diacylglycerol production. Chelation of extracellular
      calcium produced up to 70% inhibition of the adipokinetic hormone-dependent
      mobilization of lipids. Calcium-mobilizing agents, ionomycin and thapsigargin,
      greatly stimulated DG production by up to 130%. Finally, adipokinetic hormone
      caused a rapid increase of calcium uptake into the fat body. Our findings
      indicate that the action of adipokinetic hormone in mobilizing lipids from the
      insect fat body involves both cAMP and calcium as intracellular messengers.

PMID- 10064745
TI  - Lipoprotein lipase expression level influences tissue clearance of chylomicron
      retinyl ester.
AB  - Approximately 25% of postprandial retinoid is cleared from the circulation by
      extrahepatic tissues. Little is known about physiologic factors important to this
      uptake. We hypothesized that lipoprotein lipase (LpL) contributes to extrahepatic
      clearance of chylomicron vitamin A. To investigate this, [3H]retinyl ester
      containing rat mesenteric chylomicrons were injected intravenously into induced
      mutant mice and nutritionally manipulated rats. The tissue sites of uptake of 3H
      label by wild type mice and LpL-null mice overexpressing human LpL in muscle
      indicate that LpL expression does influence accumulation of chylomicron retinoid.
      Skeletal muscle from mice overexpressing human LpL accumulated 1.7- to 2.4-fold
      more 3H label than wild type. Moreover, heart tissue from mice overexpresssing
      human LpL, but lacking mouse LpL, accumulated less than half of the 3H-label
      taken up by wild type heart. Fasting and heparin injection, two factors that
      increase LpL activity in skeletal muscle, increased uptake of chylomicron [3H]
      retinoid by rat skeletal muscle. Using [3H]retinyl palmitate and its non
      hydrolyzable analog retinyl [14C]hexadecyl ether incorporated into Intralipid
      emulsions, the importance of retinyl ester hydrolysis in this process was
      assessed. We observed that 3H label was taken up to a greater extent than 14C
      label by rat skeletal muscle, suggesting that retinoid uptake requires
      hydrolysis. In summary, for each of our experiments, the level of lipoprotein
      lipase expression in skeletal muscle, heart, and/or adipose tissue influenced the
      amount of [3H]retinoid taken up from chylomicrons and/or their remnants.

PMID- 10064746
TI  - Scavenger receptor BI (SR-BI) mediates free cholesterol flux independently of HDL
      tethering to the cell surface.
AB  - In addition to its effect on high density lipoprotein (HDL) cholesteryl ester
      (CE) uptake, scavenger receptor BI (SR-BI) was recently reported to stimulate
      free cholesterol (FC) flux from Chinese hamster ovary (CHO) cells stably
      expressing mouse SR-BI, a novel function of SR-BI that may play a role in
      cholesterol removal from the vessel wall where the receptor can be found. It is
      possible that SR-BI stimulates flux simply by tethering acceptor HDL particles in
      close apposition to the cell surface thereby facilitating the movement of
      cholesterol between the plasma membrane and HDL. To test this, we used
      transiently transfected cells and compared the closely related class B scavenger
      receptors mouse SR-BI and rat CD36 for their ability to stimulate cholesterol
      efflux as both receptors bind HDL with high affinity. The results showed that,
      although acceptor binding to SR-BI may contribute to efflux to a modest extent,
      the major stimulation of FC efflux occurs independently of acceptor binding to
      cell surface receptors. Instead our data indicate that SR-BI mediates alterations
      to membrane FC domains which provoke enhanced bidirectional FC flux between cells
      and extracellular acceptors.

PMID- 10064747
TI  - The future of esophageal surgery.

PMID- 10064748
TI  - Miniature laparoscopy: quo vadis? The basic parameters of image relay and display
      systems.
AB  - BACKGROUND: Endoscopy created a new epoch in gynecology and general surgery.
      After a decade of learning experiences and expansion of laparoscopic surgery in a
      variety of areas, the need to further miniaturize the endosurgical approach
      surfaced. This, however, requires a better knowledge about the tools that
      surgeons must or wish to employ in minimal access surgery. For miniaturization,
      the quality of the image on the TV monitor is critical. METHODS: We examined two
      miniature optical systems: the quartz-fiber (2.0-2.2 mm) and the rod-lens (3.3
      mm) relay technologies. RESULTS: The smaller quartz telescope image was found to
      be brighter but lacking in other important features that are important in
      diagnosis and surgical manipulations. CONCLUSIONS: Because the detail, clarity,
      and the color display affect decision making and the course taken, the brand of
      telescope has to be selected according to the particular application. By
      following this guideline, a number of diagnostic and therapeutic procedures can
      be performed using smaller instruments with the patient under local anesthesia
      with sedation or under general anesthesia in an outpatient setting.

PMID- 10064749
TI  - Video-assisted thoracoscopic esophagectomy for esophageal cancer.
AB  - BACKGROUND: The Ivor-Lewis procedure is a radical, invasive, and effective
      procedure for the resection of most esophageal cancers. To minimize invasiveness,
      we performed thoracoscopic and video-assisted esophagectomy and mediastinal
      dissection for esophageal cancer. METHODS: From November 1995 to June 1997, 23
      patients with intrathoracic esophageal cancer, excluding T4 cancers, underwent
      thoracoscopic and video-assisted esophagectomy. Bilateral cervical dissections
      were performed as well as preparation of the gastric tube and transhiatal
      dissection of the lower esophagus. The cervical esophagus was cut using a stapler
      knife, and esophageal reconstruction was performed through the retrosternal route
      or anterior chest wall. Next, thoracoscopic mediastinal dissection and
      esophagectomy were performed. RESULTS: The mean volume of blood loss was 163 +/-
      122 ml; mean thoracoscopic surgery duration, 111 +/- 24 min; mean postoperative
      day for patients to start eating, 8 +/- 3 days; and mean hospital stay, 26 +/- 8
      days. No patient developed systemic inflammatory response syndrome
      postoperatively. Tracheal injury occurred and was repaired during the
      thoracoscopic approach in one patient. No patients died within 30 days after
      surgery. Postoperative complications included transient recurrent nerve palsy in
      five patients, pulmonary secretion retention requiring tracheotomy in two, and
      chylothorax in one. Five patients died of cancer recurrence within 1 year of
      surgery. CONCLUSIONS: Our surgical experience with thoracoscopic and video
      assisted esophagectomy indicate that it is a feasible and useful procedure.

PMID- 10064750
TI  - Endoscopic resection for submucosally invasive colorectal cancer: is it feasible?
AB  - BACKGROUND: Recent advances in colonoscopy have resulted in an increasing number
      of endoscopic resections of colorectal neoplasms. However, endoscopic resection
      of submucosal invasive cancer remains a controversial issue. METHODS: The
      subjects for this study were the surgically treated patients with submucosal
      invasive colorectal cancer. These patients were classified into two groups: those
      with versus those without preoperative endoscopic resection. Clinicopathologic
      features and prognosis were compared and analyzed. RESULTS: Fifty patients
      underwent surgery for submucosally invasive colorectal cancer. Numbers of
      patients with and without preoperative endoscopic resection were 22 and 28,
      respectively. In 36.4% of the patients, endoscopic resections were incomplete.
      Two patients in whom the preoperative endoscopic resections had revealed a
      positive cancer margin, had nodal metastasis. One of these patients also
      developed hepatic metastasis. Endoscopic findings such as diameter and shape were
      not indicative of either lymphatic or vascular invasion. There were no
      morbidities or mortalities associated with endoscopic resection or surgery.
      CONCLUSIONS: Preoperative endoscopic resection for colorectal submucosal cancer
      is feasible, provided the resection is complete. The indications for surgical
      treatment should be determined after pathologic examination.

PMID- 10064751
TI  - Utility of endoscopic ultrasonography in assessing the indications for endoscopic
      surgery of submucosal esophageal tumors.
AB  - BACKGROUND: The submucosal tumor (SMT) of the esophagus presents good indications
      for minimal invasive surgery, such as endoscopic or thoracoscopic resection.
      However, it is essential that the layer of origin be ascertained. The SMT can be
      detected as hypoechoic lesions in the wall of the esophagus, and the intramural
      location can be estimated in terms of destruction or deviation of the ultrasonic
      layer structure of the esophagus. METHODS: To test the efficacy of this approach,
      a series of patients were examined by an endoscopic ultrasonography (EUS).
      RESULTS: In one patient, the lesion was diagnosed as located in the muscularis
      mucosa, and endoscopic resection was performed. In another four patients, the
      lesions appeared to be in the proper muscle layer, and enucleation was carried
      out under thoracoscopy or open surgery. Histologically, all of the lesions were
      leiomyomas, and the EUS diagnosis was correct in all of the patients.
      CONCLUSIONS: Thus, the intramural condition of SMTs can be estimated and
      indications for endoscopic or thoracoscopic resection assessed by this approach.

PMID- 10064752
TI  - Laparoscopic-assisted colonoscopic polypectomy: technique and preliminary
      experience.
AB  - BACKGROUND: The majority of colonic polyps found at endoscopy are suitable for
      diathermy snare excision via colonoscope. Due to location or size, some are
      deemed unsafe to treat in this manner and therefore require colectomy. This study
      describes the technique and early results of a laparoscopic-assisted colonoscopic
      polypectomy technique that can be used to manage such polyps and thereby avoid
      laparotomy and colectomy. METHODS: Colonoscopy with simultaneous laparoscopy was
      utilized to locate the site of the polyp. The colon was mobilized, if required,
      and the polyp resected by electrosurgical snare via the colonoscope while the
      serosal aspect of the colon was monitored laparoscopically. RESULTS: The
      technique has been tried successfully in six patients. Three polyps were in the
      cecum and three were within the left colon. The size of the polyps ranged from 3
      to 7 cm. All polyps were benign on histological examination. The patients were
      discharged on the day following the procedure. There were no complications.
      CONCLUSIONS: The combination of laparoscopy with colonoscopic resection of a
      select group of large polyps represents a safe alternative to colonic resection.

PMID- 10064753
TI  - Increased tumor establishment and growth after open vs laparoscopic surgery in
      mice may be related to differences in postoperative T-cell function.
AB  - BACKGROUND: Previous work has demonstrated that cell-mediated immune function in
      rats is better preserved after laparoscopic than open surgery. We have also shown
      that tumors are more easily established in mice and grow larger after sham
      laparotomy than after pneumoperitoneum. The purpose of this study is to determine
      if the functional status of the cell-mediated immune system influences
      postoperative tumor growth. METHODS: Immunocompetent (study 1) and T-cell
      deficient athymic (study 2) mice were injected with mouse mammary carcinoma cells
      in the dorsal skin. Mice then underwent either no procedure, midline laparotomy,
      or carbon dioxide pneumoperitoneum. Tumor masses on postoperative day 12 were
      compared. RESULTS: In immunocompetent mice, laparotomy group tumors were nearly
      twice as large as laparoscopy group tumors (p < 0.02), which were 1.5 times as
      large as control group tumors (NS). In the athymic model, however, differences
      between the sham laparotomy and pneumoperitoneum groups were lost (p > 0.5).
      Tumors grew much larger in the athymic control mice than in the immunocompetent
      control mice (p < 0.01). CONCLUSION: We conclude that T-cell function plays a
      significant role in host containment of mouse mammary carcinoma and in the
      mechanism of differences in tumor growth observed after laparotomy and
      pneumoperitoneum.

PMID- 10064754
TI  - Micropuncture laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) significantly reduces the
      discomfort and disability typically associated with open cholecystectomy, but
      there is still room for improvement. METHODS: In order to further reduce the
      trauma of access, we have introduced a technique of micropuncture laparoscopic
      cholecystectomy (MPLC) that utilizes three 3-mm cannulae in addition to the
      standard 10-mm cannula at the umbilicus. MPLC was performed in 25 patients
      (median age, 52 years; m/f, three of 22) with symptomatic cholelithiasis.
      RESULTS: The operation was completed in all patients. The median duration of
      surgery was 75 min (range, 45-180). Sixteen patients were discharged the same day
      and nine patients the next day. All the patients had an uncomplicated recovery.
      Only eight patients requested postoperative analgesia while in hospital.
      Micropuncture exploration of the bile duct was carried out in one patient.
      CONCLUSIONS: MPLC is a feasible and safe technique that appears to improve on the
      benefits of LC; it makes the operation even more feasible as a day-surgery
      procedure.

PMID- 10064755
TI  - The use of diagnostic laparoscopy supported by laparoscopic ultrasonography in
      the assessment of pancreatic cancer.
AB  - BACKGROUND: Pancreatic resection with curative intent is possible in a select
      minority of patients with carcinomas of the pancreatic head. Diagnostic
      laparoscopy supported by laparoscopic ultrasonography combines the proven
      benefits of staging laparoscopy with high-resolution intraoperative ultrasound,
      thus allowing the surgeon to perform a detailed assessment of the pancreatic
      cancer. METHODS: In a prospective study of 26 patients with obstructive jaundice
      from a carcinoma of the head of the pancreas, the curative resectability of
      tumors was assessed by ultrasound (26 cases), computerized tomography (26 cases),
      endoscopic ultrasound (16 cases), and a combination of diagnostic laparoscopy and
      laparoscopic ultrasound (26 cases). RESULTS: The findings of ultrasound and
      computerized tomography were comparable: 50% of patients were excluded from
      curative resection. Endoscopic ultrasound provided precise information on the
      primary tumors. The accuracy of the combined diagnostic laparoscopy and
      laparoscopic ultrasound, when compared with ultrasound, computerized tomography,
      and endoscopic ultrasound, was better with respect to minute peritoneal or
      hepatic metastasis: 80.7% (or a further 30.7%) of patients did not qualify for
      curative resection. CONCLUSIONS: Diagnostic laparoscopy supported by laparoscopic
      ultrasonography enables detection of previously unsuspected metastases; thus,
      needless laparotomy can be avoided. It should therefore be considered the first
      step in any potentially curative surgical procedure.

PMID- 10064756
TI  - Small bowel obstruction secondary to stapled laparoscopically assisted vaginal
      hysterectomy.
AB  - BACKGROUND: This study analyzes the complication of small bowel obstruction
      following stapled division of the adnexa during laparoscopically assisted vaginal
      hysterectomy (LAVH). METHODS: We reviewed the records of three patients with
      small bowel obstruction following stapled LAVH. We then tested the proposed
      mechanisms of obstruction by firing endoscopic staplers across silicon tubing to
      simulate division of the adnexal structures. Staple shape, spillage, and closure
      were analyzed. RESULTS: Small bowel obstruction can result when a partially
      formed endoscopic staple hooks the small bowel. The problem can be traced to
      either spilled intraperitoneal staples or partially formed staples that adhere to
      part of the adnexal staple line. The mechanisms staple closure, spillage, and
      ability to hook small bowel were confirmed with a laboratory model. CONCLUSIONS:
      Techniques for reducing the incidence of small bowel obstruction following
      stapled LAVH include minimizing staple spillage and careful inspection of the
      adnexal staple line for partially formed staples.

PMID- 10064757
TI  - Laparoscopic treatment vs open surgery in the solution of major incisional and
      abdominal wall hernias with mesh.
AB  - BACKGROUND: Despite being one of the most exact indications, laparoscopic
      treatment of eventrations and ventral hernias is barely known among the array of
      laparoscopic techniques. METHODS: A total of 60 patients were assigned at random
      over a 3-year period to two homogeneous groups to be operated on for major
      ventral hernias with mesh. Half of them were operated upon laparoscopically and
      the rest with open surgery. Early and longer-term complications were analyzed, as
      were operative time and postoperative hospital stays. RESULTS: The two groups
      were homogeneous in terms of demographic and clinical characteristics. The group
      that was operated on laparoscopically presented a lower rate of postoperative and
      longer-term complications; similarly, surgery time was significantly lower (p <
      0.05). Hospitalization time was also significantly lower than in the group
      undergoing conventional open surgery (p < 0.05). CONCLUSIONS: Laparoscopic
      treatment of postoperative eventration and primary ventral hernia reduces
      complications and relapse rates, eliminates reintervention through mesh
      infection, reduces operative time, and considerably shortens the hospital stay.

PMID- 10064758
TI  - Hepatic cryosurgery via minilaparotomy in a porcine model: an alternative to open
      cryosurgery.
AB  - BACKGROUND: Cryosurgery of liver lesions is becoming increasingly accepted for
      the ablation of liver tumors. Attempts at laparoscopic cryosurgery have been very
      limited and often need to be converted to open laparotomy due to the complexity
      of the procedure. METHODS: Seven domestic pigs were anesthetized, and 17 small
      (0.7 cm mean diameter) tumor mimicking agar "lesions" were percutaneously placed
      in the liver. Two small subcostal incisions ( approximately 2.0 cm) were placed,
      and an endocavitary ultrasound transducer (with a 2. 4-mm cryoprobe mounted on
      it) was placed on the liver surface. Lesions were localized and directly
      punctured with one or two cryoprobes under ultrasound guidance, and a single 15
      min freeze was undertaken. The animals were then killed, and their livers were
      removed and serially sectioned. RESULTS: Total time for probe placement was
      approximately 10 min after incisions had been made. Animals tolerated the
      procedure well and all survived until they were killed. No intraabdominal
      complications were detected at exploration. Mean cryolesion dimensions were 3.0
      cm (single probe) and 3.3 cm (dual probe) (p > 0.05). Positive margins were
      detected in one lesion treated with a single probe, and in none of the lesions
      treated with dual probes. Mean margins were 0.9 cm: 1.2 cm for the single probe
      and dual probe techniques, respectively. Liver surrounding control agar lesions
      demonstrated a thin rim of necrosis, approximately 0.5 mm wide. CONCLUSIONS: We
      conclude that minilaparotomy is an effective, safe, and simple method for
      performing hepatic cryosurgery in this animal model. This minimally invasive
      technique may benefit a subset of patients with lesions in accessible locations.
      Lesions in posterior locations may not be as amenable to this technique due to
      deterioration of ultrasound image quality in the far field.

PMID- 10064759
TI  - Chest physiotherapy does not improve the outcome in laparoscopic fundoplication
      and vertical-banded gastroplasty.
AB  - BACKGROUND: Chest physiotherapy is a common practice after open reflux and
      obesity surgery. It is now possible to perform fundoplication and vertical banded
      gastroplasty (VBG) by the laparoscopic technique. The aim of this study was to
      evaluate in a prospective, randomized, controlled trial whether chest
      physiotherapy affects the postoperative course. METHOD: A series of 40 patients
      underwent laparoscopic fundoplication; another 40 underwent laparoscopic VBG.
      Twenty patients in each series received prophylactic chest physiotherapy; the
      other 20 served as control patients and were not given any information or
      training. RESULTS: Postoperatively, all patients had a significant reduction in
      respiratory function, measured as oxygen saturation, forced vital capacity, and
      peak expiratory flow, but the differences between the groups within each series
      were not significant. Postoperatively, one patient in the VBG treatment group had
      hypoxemia (SaO2 <92%) versus two control patients. One control patient developed
      postoperative pneumonia. CONCLUSIONS: This study indicates that routine chest
      physiotherapy is not necessary in patients undergoing laparoscopic upper
      gastrointestinal surgery, such as fundoplication and VBG.

PMID- 10064760
TI  - Unexpected gallbladder cancer after laparoscopic cholecystectomy: an emerging
      problem? Reflections on four cases.
AB  - Gallbladder cancer (GC) has been reported in 0.3-1.5% of cholecystectomies. Since
      the introduction of laparoscopic surgery, cholecystectomies have increased and
      occult GC may therefore be more frequent. Herein we analyze our own experience to
      determine whether there was an increase in GC. We also evaluate the risk factors
      for this outcome. Four patients with GC undiagnosed before surgery (four of 602
      cases, or 0.66%) were submitted to laparoscopic cholecystectomy. The percentage
      in patients who underwent open surgery was 0.28% (two of 714 cases). Without
      reoperation, three patients died in the laparoscopic group and one is alive at 12
      months. Trocar site metastasis was not observed. Although the percentage of GC
      (0.28% versus 0.66%) increased, the percentage is still in the referred average.
      Undiagnosed GC is on the increase. Examination of the gallbladder and a frozen
      section, if necessary, are recommended. Calcified gallbladders, age >70 years, a
      long history of stones, and a thickened gallbladder all represent significant
      risk factors.

PMID- 10064761
TI  - Combined abdominal wall paresis and incisional hernia after laparoscopic
      cholecystectomy.
AB  - A case of combined abdominal wall paresis and incisional hernia after
      laparoscopic cholecystectomy is reported. The paresis possibly occurred by a
      lesion of the N. intercostalis when extending the incision for stone extraction.
      Possibly the paresis was a predisposing factor for the development of an
      incisional hernia. The causes of abdominal wall paresis are explored with a
      review of the literature. In spite of minimal trauma to the anterior abdominal
      wall in laparoscopic procedures, the risk of iatrogenic lesions remains.

PMID- 10064762
TI  - Perforated epiphrenic diverticulum treated by video laparoscopy.
AB  - We describe the case of an esophageal perforation that occurred after an
      endoscopic examination for epigastric pain 11 days before being referred to our
      institution. After 5 days of conservative management with total parenteral
      nutrition, left chest drainage, and broad-spectrum antibiotics, we decided to
      perform an videolaparoscopic jejunostomy for feeding with distal esophageal
      exclusion and a cervical esophagostomy. In the operating room, however, we found
      that the site of the perforation was an epiphrenic diverticulum. Treatment was
      diverticulectomy through videolaparoscopy with manual and mechanic suture. The
      postoperative evolution was successful, and the patient was discharged 8 days
      after surgery.

PMID- 10064763
TI  - Malignant pseudoachalasia.
AB  - During the course of a laparoscopic Heller myotomy, a patient thought to have
      primary achalasia was found instead to have an adenocarcinoma of the
      gastroesophageal junction. Aspects of this patient's clinical course, which are
      exemplary of malignant pseudoachalasia, are discussed, as are ways in which this
      not uncommon error in diagnosis can be avoided.

PMID- 10064764
TI  - Venous gas embolism during endoscopy.
AB  - Venous gas embolism is a rare but serious complication of laparoscopic and
      endoscopic procedures. We describe the case of a 33-year-old woman with a
      strictured hepaticojejunostomy anastomosis who was treated with transabdominal
      endoscopic balloon dilation. During the procedure, she suffered a venous gas
      embolus with immediate cardiovascular collapse. After treatment with pressors,
      electrical cardioversion, and multiple aspirations of the right ventricle, the
      patient recovered fully. We reviewed all reported cases of venous gas embolism
      during endoscopy over the past 30 years and identified multiple risk factors. We
      suggest precautions to minimize future complications in patients at increased
      risk.

PMID- 10064765
TI  - Colocutaneous fistula after percutaneous endoscopic gastrostomy in a remnant
      stomach.
AB  - An 82-year-old woman underwent percutaneous endoscopic gastrostomy (PEG) 5 years
      after partial gastrectomy for cancer. Four months after PEG insertion, a
      colocutaneous fistula was noted at exchange of the PEG tube. Colocutaneous
      fistula is a rare and major complication of PEG with 10 reported cases to date.
      In eight of the 11 reported cases, including this case, fistulas appeared late
      (>6 weeks) after PEG insertion. This complication may heal after removal of the
      PEG alone, if the fistula has formed completely; otherwise a surgical approach is
      necessary for the treatment. Since five of the 11 reported patients had
      previously undergone abdominal surgery, prior abdominal surgery may increase the
      risk of a colonic injury after PEG. Open surgical gastrostomy is a wiser option
      when performing gastrostomy in patients with prior abdominal surgery.

PMID- 10064766
TI  - Bowel obstruction caused by dislocation of a suprapubic catheter.
AB  - In patients with a suprapubic catheter, the differential diagnosis of acute lower
      abdominal pain must include a possible dislocation of this device. We report a
      case that illustrates such a complication, leading to bowel obstruction in our
      patient.

PMID- 10064767
TI  - Pneumoperitoneum from an eroded T-fastener.
AB  - We present a case of late gastric perforation caused by retained T-fasteners
      after removal of a percutaneous endoscopic gastrostomy tube. We emphasize that
      timely removal of these fasteners is important in preventing this complication.

PMID- 10064769
TI  - EndoScope: world literature reviews 

PMID- 10064768
TI  - Retained fecalith after laparoscopic appendectomy.
AB  - An intraabdominal abscess developed from a retained fecalith following
      laparoscopic appendectomy. We discuss the prevention and management of retained
      fecaliths in light of the numerous reports of retained gallstones.

PMID- 10064770
TI  - Totally endoscopic Ivor Lewis esophagectomy.
AB  - Esophagectomy is associated with significant risks of perioperative morbidity and
      mortality, as well as prolonged convalescence due to effects of the incisions
      used for conventional surgical access. Because the outcome of this procedure is
      palliative in the majority of patients, it is possible that laparoscopic
      techniques could improve initial postoperative outcomes and therefore make
      surgery more acceptable for patients with esophageal cancer. A new technique is
      described for Ivor Lewis esophagectomy, which incorporates a hand-assisted
      laparoscopic approach for gastric mobilization and a thoracoscopic approach for
      esophageal dissection and anastomosis. Initial experience in two patients has
      been encouraging, with postoperative hospital stay and convalescence shortened.

PMID- 10064771
TI  - Safety of adrenal vein ligation during endoscopic adrenalectomy: a technical
      note.
AB  - Endoscopic adrenalectomy has been recommended for the treatment of several benign
      adrenal diseases. The safety of this procedure largely depends on a careful
      surgical dissection and appropriate hemostatic technique. An established
      slipknotting technique was employed to control the main adrenal vein in a
      consecutive series of 14 patients undergoing endoscopic adrenalectomy. The
      operative steps to ligate the adrenal pedicle are described. A Medline search
      also was conducted to identify all reported bleeding episodes associated with
      this procedure. All attempted ligatures of the main adrenal vein were completed
      successfully by the described technique, and none of our patients required
      perioperative blood transfusion. Twenty-eight episodes of bleeding collected from
      the literature were analyzed. Hemorrhagic accidents related to dislodgement of
      clips were documented at least in three patients. The cause of bleeding was
      unspecified in 10 patients. Extracorporeal ligation of the main adrenal vein is
      feasible, safe, and advisable to prevent the occurrence of hemorrhage during
      endoscopic adrenalectomy.

PMID- 10064772
TI  - Needlescopic or minisite cholecystectomy.
AB  - Needlescopic or minisite cholecystectomy is laparoscopic cholecystectomy done
      through tiny ports from 1.4 mm to 3 mm in size. This refinement of conventional
      laparoscopic cholecystectomy reduces further the invasiveness of the operation
      and gives an improved cosmetic effect. This series describes the result of 36
      needlescopic cholecystectomies done between February 1996 and April 1997.
      Patients with acute cholecystitis were excluded. There were two conversions to
      conventional laparoscopic surgery and no conversions to open surgery. Thirty-four
      patients were successfully treated by this technique. Analgesic consumption and
      cosmetic result was superior compared to a previous published series of
      conventionally done cases in the same department.

PMID- 10064773
TI  - Safe creation of pneumoperitoneum using an optical trocar.
AB  - The blind insertion of the Veress needle and the first trocar may cause serious
      complications. Therefore, many surgeons perform a minilaparotomy to safely
      position the first trocar. However, especially in obese patients, the dissection
      may be difficult and time consuming. As an alternative, optical trocars can be
      safely positioned under direct visualization. We report on our experience with
      the Optiview trocar in 200 patients and describe our preferred insertion
      technique. In our opinion, optical trocars are safe and easy to handle, offering
      several advantages over the use of the Veress needle and the minilaparotomy.

PMID- 10064774
TI  - Video-assisted gastrostomy: a modification.
AB  - Surgical centers that treat esophageal cancer need to create a simple and easy
      method to feed patients who suffer from complete occlusion of the upper
      alimentary tract. The purpose of this work is to present our own modification of
      a laparoscopic feeding gastrostomy, which is based on our own experience and
      previously published methods. Our system requires only two trocars and can be
      done under general or local anesthesia. It consists of exteriorizing a stomach
      fragment through a 12-mm opening in the skin under video control. The newly
      created gastrostomy forms a channel in the abdominal wall that is long narrow and
      enough to allow a 24-F catheter to be inserted without serious leakage. The
      method was applied satisfactorily to 11 patients, with a mean observation time of
      3.5 months. It offers the patient an ongoing nutrition gastrostomy for early use.
      After 3 weeks, the gastrostomy can be used on a temporary basis by inserting the
      catheter during the feeding time and afterward withdrawing it with the gauze pad
      still attached. We have found this procedure to be a simple, easy, and cost
      effective alternative to supplying nutrition to patients with complete upper
      alimentary tract stenosis. Moreover, it is superior to previously described
      methods.

PMID- 10064775
TI  - Brush dissection technique in laparoscopic cholecystectomy.

PMID- 10064776
TI  - An inexpensive laparoscopic gallbladder retrieval bag.

PMID- 10064777
TI  - Endoscopic thyroid and parathyroid surgery.

PMID- 10064780
TI  - News and notices 

PMID- 10064779
TI  - Correct use of the gasless LaparoTenser system.

PMID- 10064781
TI  - Activation of the hypothalamic-pituitary axis in adrenalectomised rats:
      potentiation by chronic stress.
AB  - The influence of chronic stress on the status of the hypothalamo-pituitary
      adrenal (HPA) axis of sham-operated and adrenalectomised rats was assessed.
      Animals underwent bilateral adrenalectomy (ADX) and 3 days later they were either
      left undisturbed or subjected daily to immobilization for 2 h each morning for 14
      days (chronic IMO). In situ hybridization histochemistry revealed that ADX
      increased corticotropin-releasing factor (CRF) mRNA levels in the paraventricular
      nucleus of the hypothalamus (PVN) and proopiomelanocortin (POMC) mRNA levels in
      the anterior pituitary, in both control and chronically stressed rats as measured
      on the day following the last exposure to stress. Chronic IMO increased CRF mRNA
      levels in the PVN and POMC mRNA levels in the anterior pituitary of sham-operated
      rats, as measured on the day following the last exposure to stress. Chronic IMO
      potentiated the increase in CRF mRNA in the PVN following ADX and resulted in
      further increases in CRF mRNA above levels seen in adrenal-intact animals.
      Finally, chronic stress, while not altering basal ACTH levels of ADX rats,
      reduced the ACTH response of these animals to a novel stressor (tail-shock for 30
      min). These results suggest that chronic stress exerts a stimulatory influence at
      the hypothalamic level that is partially restrained by daily stress-induced
      glucocorticoid release. Despite the potentiation by chronic stress of CRF mRNA
      content in the PVN of ADX rats, a blunted circulating ACTH response to an acute
      short-term stressor was apparent in ADX-chronically stressed rats, suggesting
      that chronic stress might also alter POMC processing and/or ACTH secretory
      patterns in the anterior pituitary in ADX animals.

PMID- 10064782
TI  - The timing of galvanic vestibular stimulation affects responses to platform
      translation.
AB  - We compared the effects of galvanic vestibular stimulation applied at 0, 0.5, 1.5
      and 2.5 s prior to a backward platform translation on postural responses. The
      effect of the galvanic stimulation was largest on the final equilibrium position
      of the center of pressure (CoP). The largest effects occurred for the 0.5 and 0-s
      pre-period, when the dynamic CoP pressure changes in response to both the
      galvanic stimulus and the platform translation coincided. The shift in the final
      equilibrium position was also larger than the sum of the shifts for the galvanic
      stimulus and the platform translation alone for the 0.5 and 0-s pre-periods. The
      initial rate of change of the CoP response to the platform translation was not
      significantly affected in any condition. Changes in the peak CoP position could
      be accounted for by local interaction of CoP velocity changes induced by the
      galvanic and translation responses alone, but the changes in final equilibrium
      position could only be accounted for by a change in global body orientation.
      These findings suggest that the contribution of vestibulospinal information is
      greatest during the dynamic phase of the postural response, and that the
      vestibular system contributes most to the later components of the postural
      response, particularly to the final equilibrium position. These findings suggest
      that a nonlinear interaction between the vestibular signal induced by the
      galvanic current and the sensory stimuli produced by the platform translation
      occurs when the two stimuli are presented within 1 s, during the dynamic phase of
      the postural response to the galvanic stimulus. When presented at greater
      separations in time, the stimuli appear to be treated as independent events, such
      that no interaction occurs.

PMID- 10064783
TI  - Characterization and localization of CD38 in the vertebrate eye.
AB  - CD38 is a 42-kDa type II transmembrane glycoprotein that has been shown to
      catalyze the synthesis and hydrolysis of cyclic ADP-ribose, a metabolite with
      well-known calcium mobilizing properties independent of IP3. In this report,
      characterization and localization of CD38 in the porcine and rat eyes were
      carried out. Western blot analysis of a purified microsomal eye extract detected
      a single 42-kDa protein band characteristic of CD38. Subcellular fractionation
      studies indicate the presence of ADP-ribosyl cyclase and NADase activities in the
      nuclear, membrane and microsomal fractions. Immunohistochemical staining of the
      rat retina showed the expression of CD38 in three distinct layers: the ganglion
      cell layer, inner nuclear layer and the pigmented epithelium. In the lens, the
      lenticular epithelium and lens cells were also immunoreactive for CD38 while in
      the ciliary body, both the pigmented and non-pigmented epithelium also showed the
      presence of CD38. For the first time, the presence of CD38/ADP-ribosyl cyclase
      was detected in the vertebrate eye.

PMID- 10064784
TI  - Cocaine and lidocaine have additive inhibitory effects on the GABAA current of
      acutely dissociated hippocampal pyramidal neurons.
AB  - Inhibition mediated by gamma-aminobutyric acid (GABA) is a major target for the
      central actions of cocaine and lidocaine, which can result in seizures,
      especially when these drugs are abused in combination. In the present study, we
      investigated how cocaine and lidocaine interact to depress GABA current (IGABA),
      recorded by the whole-cell technique in freshly isolated rat hippocampal neurons.
      Cocaine depressed IGABA in a concentration dependent manner, such that cocaine
      was more potent against lower than higher GABA concentrations: the cocaine IC50
      was 0.13, 0.62 and 1.2 mM for GABA at 2, 10 and 100 microM, respectively. Cocaine
      depressed IGABA to the same extent in the absence and presence of 1 microM
      tetrodotoxin, indicating that cocaine inhibition of IGABA is distinct from its
      Na+ channel blocking action. Lidocaine reversibly depressed IGABA evoked by 10
      microM GABA, with an IC50 of 9.8 mM. In the presence of 3 mM lidocaine, 0.3 mM
      cocaine depressed IGABA (10 microM GABA) to 30+/-7%. The significantly greater
      depression by the combined agents (p<0.05) indicates additive effects on the GABA
      receptor/channel complex, which are likely to contribute to the additive
      convulsant effects noted when these drugs are abused in combination.

PMID- 10064785
TI  - Glucocorticoid receptor antagonists in the hippocampus modify the negative
      feedback following neural stimuli.
AB  - The effects of local glucocorticoid receptor antagonists implanted into the
      dorsal hippocampus on the hypothalamo-pituitary-adrenal (HPA) axis responses
      following neural stimuli in freely moving rats, as well as their effects on the
      negative feedback exerted by dexamethasone (DEX) was studied in male rats. In
      animals with hippocampal cholesterol implants, photic and acoustic stimuli caused
      depletion in median eminence (ME) CRH-41 and a consequent rise in plasma ACTH and
      corticosterone levels. These effects were inhibited by systemic DEX, and the
      latter phenomenon was partially reversed by hippocampal implants of
      glucocorticoid (GR) and to a lesser degree by mineralocorticoid (MR) receptor
      antagonists. These data indicate that GR and MR receptors in the hippocampus play
      a role in the glucocorticoid negative feedback on the HPA axis, although the
      hippocampus may have also a modulatory effect, which does not depend on
      glucocorticoids.

PMID- 10064786
TI  - Adaptive fusimotor reflex control in the decerebrate cat.
AB  - The effect of electrical stimulation of cutaneous afferents in the superficial
      peroneal nerve on the locomotor discharges of single medial gastrocnemius gamma
      motoneurones has been investigated in a decerebrate cat preparation. Units were
      classified as static (n=9) or dynamic (n=7) indirectly on the basis of their
      resting and locomotor discharge characteristics. Brief trains of stimulation, at
      2 and 3xthreshold (T), were applied at rest and during locomotion. Responses were
      assessed by calculating the change in mean rate during the 100 ms after stimulus
      onset compared with a control period. At rest, static and dynamic gamma
      motoneurones showed opposite responses. Static neurones were excited while
      inhibition was dominant with dynamic neurones. Effects were always present at 2T.
      During locomotion, inhibitory responses occurred with both types of gamma
      motoneurone and excitation was not apparent. The inhibition of static neurones
      was maximum during (four units) or between (five units) EMG bursts and minimum in
      the opposite phase of EMG activity. For dynamic neurones, inhibition was not
      related to locomotor phase. Generally (six of seven units), the inhibition of
      dynamic gamma-motoneurones was reduced throughout the step cycle, including
      phases in which background discharge rates were comparable to resting levels.
      Latencies of response were measured from peristimulus time histograms.
      Subtraction of peripheral conduction times gave estimated central delays of
      locomotor inhibition for static (2.4+/-0.2 ms, n=6; mean+/-S.E.M.) and dynamic
      (2.2+/-0.2 ms, n=7) gamma-motoneurones that were not significantly different
      (P>0. 1) and are consistent with spinal oligosynaptic pathways. We conclude that
      low threshold skin afferents from the foot dorsum are capable of influencing both
      types of gamma-motoneurone during walking through short latency spinal inhibitory
      pathways. Further, a highly specific (reciprocal) control of the reflex responses
      of static and dynamic gamma-efferents occurs that is dependent upon behavioural
      context. The results are discussed in relation to cutaneous effects on gamma
      motoneurones which are suggested to form an adaptive control system.

PMID- 10064787
TI  - Cardiovascular effects of catecholamines injected into the DBB of rats, influence
      of urethane anaesthesia and local colchicine.
AB  - In a previous publication it was shown that 1 microgram colchicine injected into
      the diagonal band of Broca (DBB) produced a significant decrease in femoral
      artery blood pressure (and/or volume) measured in urethane-anaesthetised rats. In
      order to test if the central catecholamines were involved in this effect, guide
      cannulae were implanted in the DBB and a catheter in the femoral artery. On-line
      pressure recordings were taken before during and after alpha1, alpha2 and beta
      adrenoreceptor agonists and antagonists were injected into the region of the DBB
      of non-anaesthetised and urethane anaesthetised male Wistar rats with and without
      injection of colchicine. Arterial pressure was significantly increased in the non
      anaesthetised rats (114.6+/-2.6 n=11 vs. 149.3+/-3.3 mmHg n=12, p<0.01) yet
      significantly reduced (82.0+/-3.9 n=11 vs. 63.8+/-4.5 mmHg n=12, p<0.01) in the
      urethane treated rats by the alpha2 agonist clonidine. The alpha2 antagonist
      yohimbine blocked these effects in both preparations. In contrast, the beta
      adrenoreceptor agonist isoprenaline produced a significant decrease in arterial
      pressure in both preparations (107.7+/-3.9 n=11 vs. 85.9+/-4.0 mmHg n=12, p<0.01)
      (102.6+/-6.7 n=11 vs. 81.7+/-3.4 mmHg n=12, p<0.01) and this effect was blocked
      by the beta antagonist propranolol. Colchicine injected into the DBB abolished
      the effects of the alpha2 agonist and antagonist in the non-anaesthetised but not
      the anaesthetised rats. The responses to the beta agonist and antagonist were not
      greatly affected by the colchicine in the non-anaesthetised rats whereas in the
      anaesthetised rat beta agonist injection tended to totally depress arterial
      pressure. These results suggest that the sympathetic nervous system in the DBB
      plays a significant role in the central control of arterial pressure and that the
      alpha2 component is significantly affected by the state of anaesthesia.

PMID- 10064788
TI  - Mechanisms of apoptosis in PC12 cells irreversibly differentiated with nerve
      growth factor and cyclic AMP.
AB  - PC12 cells treated with cAMP become irreversibly differentiated and die by
      apoptosis when deprived of trophic support, instead of dedifferentiating and
      reentering the cell cycle. To approach the molecular mechanism underlying the
      cAMP-induced switch from differentiation/proliferation to apoptosis, we compared
      three sequential markers of a candidate apoptogenic signal transduction pathway
      (ceramide, free radicals and NF-kappaB), after trophic factor withdrawal in PC12
      cells before and after irreversible differentiation. Serum withdrawal increased
      ceramide and free radical production regardless of the state of differentiation
      of the cells. It was followed by cell death, however, only in the absence of NGF
      and/or cAMP, and was no longer required for apoptosis in NGF/cAMP-differentiated
      cells. NGF and cAMP withdrawal sufficed. NF-kappaB was activated by NGF
      withdrawal in reversibly differentiated PC12 cells during dedifferentiation and
      reentry into the cell cycle, whereas in NGF/cAMP-differentiated cells, it was
      activated, at a late stage of the apoptotic process, concomitantly with cell
      death. These results show that a serum factor inhibits ceramide-dependent
      apoptosis upstream of ceramide and free radical production, whereas NGF- and cAMP
      dependent mechanisms inhibit apoptosis either downstream or parallel to these
      events. After terminal differentiation by cAMP, apoptosis appears to be initiated
      from the second site, consistent with the serum independence of these cells and
      the absence of ceramide and free radical production when the NGF/cAMP-dependent
      inhibitions are released. The differential regulation of NF-kappaB appears to be
      an important step in the switch from mitosis to apoptosis that occurs during
      irreversible differentiation of PC12 cells by cAMP.

PMID- 10064789
TI  - Effects of tolcapone upon soluble and membrane-bound brain and liver catechol-O
      methyltransferase.
AB  - The present study was aimed to evaluate the sensitivity of soluble (S) and
      membrane bound (MB) catechol-O-methyltransferase (COMT) from rat brain and liver
      to inhibitors which interact with the enzyme as competitive (tropolone), non
      competitive (S-adenosyl-l-homocysteine; SAHC) and tight-binding (tolcapone and
      3,5-dinitrocatechol) inhibitors. COMT activity was evaluated by the ability to
      methylate adrenaline (0.1 to 2000 microM) to metanephrine in the presence of a
      saturating concentration of the methyl donor (S-adenosyl-l-methionine). When
      using a fixed amount of total protein (2 micrograms/ml), but variable
      concentrations of COMT, the inhibitory potency of tolcapone upon S- and MB-COMT
      activity in the brain was in the low nM range (IC50's of 2 and 3 nM,
      respectively), whereas in liver the IC50 values for tolcapone against liver MB-
      and S-COMT (IC50's of 123 and 795 nM, respectively) were markedly higher than
      those observed in the brain. By contrast, when inhibition studies were performed
      with a fixed concentration of COMT (15 nM), as determined by the Ackermann-Potter
      equation, tolcapone was found to be endowed with the same potency (in the low nM
      range) in inhibiting S- and MB-COMT from both brain and liver. As for tolcapone,
      3,5-dinitrocatechol was more potent against MB- than against S-COMT when a fixed
      amount of total protein was used, but showed the same potency when a fixed
      concentration of COMT was used. Tropolone, a competitive inhibitor, was much less
      potent than tolcapone and 3,5-dinitrocatechol in inhibiting S- and MB-COMT from
      both brain and liver and its potency was found not to depend on enzyme
      concentration. SAHC, a non-competitive inhibitor, behaved similarly to tight
      binding inhibitors when a fixed amount of total protein was used. By contrast,
      when a fixed amount of enzyme was used, SAHC was found to be endowed with the
      same potency against S- and MB-COMT from brain and liver. In the final series of
      experiments the inhibitory effect of tolcapone was examined under in vitro ex
      vivo conditions, using the same concentration of COMT (15 nM). One hour after its
      oral administration, tolcapone (0.3 to 30 mg/kg) was found to be much more potent
      against MB-COMT than against S-COMT. In the liver, 0.3 mg/kg tolcapone resulted
      in 82% inhibition of MB-COMT and 31% inhibition of S-COMT. In the brain, 3.0
      mg/kg tolcapone inhibited 78% MB-COMT, whereas S-COMT activity was reduced by 38%
      only. In conclusion, the results reported here show that tolcapone is
      particularly potent in inhibiting MB-COMT from liver and brain under in vivo
      experimental conditions, though it does not discriminate between MB- and S-COMT
      under in vitro experimental conditions when using the same amount of enzyme in
      the assay.

PMID- 10064790
TI  - Extracellular cholecystokinin levels in the rat spinal cord following chronic
      morphine exposure: an in vivo microdialysis study.
AB  - Conflicting results concerning the issue of whether or not chronic morphine
      exposure induces an increase in CCK biosynthesis have been found in many CNS
      sites, including the spinal cord, where CCK activity may contribute to the
      facilitation of the development of opiate tolerance. The present study was
      undertaken in order to monitor the extracellular level of CCK under spontaneous
      and stimulus-evoked release in the spinal cord dorsal horn of drug naive and
      morphine tolerant rats. Tolerance was induced by implantation of two morphine
      pellets (2x75 mg) which induced a stable morphine plasma concentration after 48 h
      post-implantation. The tail-flick test and naloxone precipitated withdrawal were
      used as indexes of tolerance and dependence to morphine. The effect of morphine
      pellet implantation on basal and K+-induced release of CCK-like immunoreactivity
      (CCK-LI) in the rat dorsal horn were monitored with in vivo microdialysis 96 h
      after implantation of morphine or placebo pellets, when rats showed tolerance and
      dependence. Basal CCK levels were below the detection limit of the assay (0.6 pM)
      in both tolerant and normal animals. K+ (100 mM) in the perfusion medium induced
      a more than 3-fold increase of the extracellular level of CCK-LI in control
      animals, and a more than 4-fold increase on CCK-LI in morphine-pellet implanted
      animals. However, this difference was not significant. In addition, naloxone (2
      mg/kg; i.v.), did not induce any change in the extracellular level of CCK in
      either group. The present study suggests that the modulatory interaction between
      CCK and opioids in the development of tolerance in the spinal cord may occur
      without necessarily increasing the extracellular level of CCK. Another possible
      explanation of the finding is that the microdialysis technique is not sensitive
      enough to detect differences in unstimulated CCK levels in normal and tolerant
      animals.

PMID- 10064791
TI  - The responses of muscle spindles to small, slow movements in passive muscle and
      during fusimotor activity.
AB  - We have previously shown that movement detection thresholds at the human elbow
      joint were less than a degree of joint rotation in the passive limb but were
      higher if they were measured while subjects co-contracted elbow muscles [A.K.
      Wise, J.E. Gregory, U. Proske, J. Physiol., 508 (1998) 325-330]. Here we report
      observations on the responses of muscle spindles of the soleus muscle of the
      anaesthetised cat to determine their ability to signal small length changes in
      the passive muscle and during a contraction, under conditions resembling those of
      the human experiments. After appropriate conditioning of the muscle to control
      for history effects, primary endings of muscle spindles showed thresholds to ramp
      stretch at 20 micrometers s-1 of between less than 5 micrometers and 15
      micrometers, which translates to 0.05 degrees -0.15 degrees of human elbow joint
      rotation. Thresholds were much higher following conditioning to introduce slack
      in the muscle. Since during a voluntary contraction there is likely to be
      alpha:gamma co-activation, responses of spindles were also recorded during slow
      stretches (100 micrometers at 20 micrometers s-1) during static fusimotor
      stimulation, dynamic fusimotor stimulation, combined fusimotor stimulation and
      fusimotor plus skeletomotor stimulation. Invariably, responses to passive stretch
      were larger than during motor stimulation. It is concluded that spindles are
      sensitive enough to signal fractions of a degree of elbow joint rotation and that
      the rise in threshold observed during a voluntary contraction may be accounted
      for by the actions of fusimotor and skeletomotor axons on spindle stretch
      responses.

PMID- 10064792
TI  - Photic entrainment and induction of immediate-early genes within the rat
      circadian system.
AB  - Immediate-early genes (IEGs) are transiently expressed within the rodent
      circadian system in response to nocturnal light. The two most studied light
      induced IEGs within this system are Fos and Jun-B. Molecular expression of these
      two genes within the hypothalamic suprachiasmatic nucleus (SCN) correlates with
      light-induced behavioral phase shifts. Previous studies of the role of Fos and
      Jun-B in circadian clock resetting have used light stimuli that induce strong
      phase shifts. However, the relationship of Fos and Jun-B expression in the SCN
      and light-induced phase shifts in an entrainment context is undocumented in rats.
      In this study, male rats for which the free running period was determined were
      entrained to a 0.5 h:23.5 h LD cycle. On the fifteenth day of stable entrainment,
      the entraining light pulse was reduced to 10 min. Animals were killed 50 min
      later and brains were processed for IEG immunocytochemistry. Strong Fos induction
      was observed in the SCN and the intergeniculate leaflet (IGL). Strong Jun-B
      immunoreactivity was observed only in the SCN whereas Jun-B labeling in the IGL
      was weak. Significant correlations were obtained between the magnitude of light
      induced IEGs in the SCN and the magnitude of the daily phase shift required for
      stable entrainment to the 0.5 h:23.5 h LD cycle. Further, a significant
      correlation was observed between the number of Fos and Jun-B immunoreactive cells
      in the SCN and IGL. These data suggest that the magnitude of Fos and Jun-B
      induction within the SCN is related to the magnitude of the daily phase shift
      required for stable entrainment.

PMID- 10064793
TI  - Nitric oxide (NO) release by glutamate and NMDA in the dorsal horn of the spinal
      cord: an in vivo electrochemical approach in the rat.
AB  - Glutamate acts as a neurotransmitter of primary afferent messages in the spinal
      cord. Through glutamatergic mechanisms nitric oxide (NO) is also a potential
      intermediary in the transmission of sensory messages, particularly nociceptive,
      at the spinal level. The aim of the present study was, by using electrochemical
      monitoring of NO, to determine if the activation of glutamatergic transmission,
      particularly through NMDA receptors, could increase NO production within the
      dorsal horn of the lumbar spinal cord in the rat. 30 micrometers diameter treated
      carbon fiber electrodes coated with nickel-porphyrine and Nafion(R), and
      associated with differential normal pulse voltammetry, have been used in vivo to
      monitor NO within the dorsal horn of the lumbar spinal cord of decerebrated
      spinalized rats. A NO-dependent peak of oxidation current (650 mV vs. Ag-AgCl),
      remaining stable for up to 3 h (+/-5%) could be detected under basal conditions,
      which indicates that significant amounts of NO are produced continuously. The non
      competitive N-methyl-d-aspartate (NMDA) channel blockers, Ketamine (100 mg kg-1
      i.p.) and MK-801 (10 mg kg-1 i.p.), decreased the voltammograms to 70+/-5% and
      69+/-2% of controls at 120 min, respectively. Glutamate (10 mM), when directly
      superfused upon the spinal cord (20 min at 50 microliters min-1) induced a rapid
      and significant increase of the 650 mV peak, with a maximum at around 90 min
      (148+/-6% of control) followed by a slow decay (138+/-4% of control at 150 min).
      This increase could be totally reversed or blocked by i.p. injection of 100 mg kg
      1 of Ketamine. NMDA (30 mg kg-1 i.p.) induced a long-lasting increase in the
      peaks (149+/-11% at 90 min and 162+/-20% at 120 min), which was also fully
      reversed by Ketamine or MK-801. These results provide in vivo direct evidence of
      a glutamate- and/or NMDA-induced release of NO at the spinal level, and is
      discussed in relation to the glutamatergic transmission of primary afferent
      messages.

PMID- 10064794
TI  - Early and prolonged widespread increase in brain protein synthesis following a
      single electroconvulsive shock in free-moving rats.
AB  - The autoradiographic method with l-[35S] methionine ([35S]Met) was used to
      determine the effect of a single electroconvulsive shock (ECS) on local rates of
      protein synthesis in the adult rat brain in free-moving conditions. We have
      estimated the relative contribution of methionine derived from protein breakdown
      to the intracellular precursor amino acid pool (tRNA pool) for protein synthesis.
      In steady-state conditions, we showed a large contribution (around 60%) of Met
      recycling into the precursor pool (lambda=0.37+/-0.11), after a single ECS. In
      all the 36 brain regions examined, apparent rates of protein synthesis were
      greatly increased (21-50%) 3 h after a single ECS indicating a generalized effect
      in rat brain. This ECS-induced activation of the overall rate of brain protein
      synthesis persisted for at least 24 h after cessation of ECS. This is consistent
      with the hypothesis that electroconvulsive therapy is associated with long-term
      molecular changes in neuronal activity.

PMID- 10064795
TI  - Analysing metabotropic glutamate group III receptor mediated modulation of
      synaptic transmission in the amygdala-kindled dentate gyrus of the rat.
AB  - Metabotropic glutamate receptors (mGluRs) provide a powerful control of synaptic
      transmission in the hippocampus and may serve as a target for drug development in
      human temporal lobe epilepsies. Agonists and antagonists at these receptors
      influence the development and propagation of seizures in some animal models of
      epilepsy. Experimental seizures can change the level of expression of mGluRs in
      the rat hippocampus. In the human dentate gyrus of patients suffering from
      temporal lobe epilepsy (TLE), group III mGluR mediated inhibition of synaptic
      transmission is almost lost in the sub-group with Ammon's horn sclerosis. We
      tested the modulation of synaptic transmission by the group III mGluR specific
      agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) in the dentate gyrus outer
      molecular layer in control and amygdala-kindled rats, a common model for TLE.
      Extracellular field potential recordings upon subthreshold stimulation of lateral
      perforant path fibers were measured simultaneously in the outer molecular layer
      and granule cell layer. Analysis of 'paired-pulse' characteristics in the absence
      and presence of L-AP4 and group III mGluR mediated inhibition of synaptic
      transmission in the lateral perforant path revealed no significant alterations in
      fully kindled rats. Since there is no evidence of altered L-AP4 responses, a loss
      of group III mGluR function, particularly that of subtype mGluR8, seems not
      necessary for the kindling epilepsy.

PMID- 10064796
TI  - Heightened resistance of the neonatal brain to ischemia-reperfusion involves a
      lack of mitochondrial damage in the nerve terminal.
AB  - Mitochondria are known targets of ischemia-reperfusion injury in adult brain.
      Although neonates are more resistant to ischemic episodes, the mechanisms
      accounting for this are not yet fully understood. The aim of this study therefore
      was to determine whether a difference in post-ischemic mitochondrial function may
      play a role in the heightened recovery of the neonatal brain following ischemia
      reperfusion. We have therefore compared the effects of an in vitro model of
      ischemia on the enzymes of the mitochondrial respiratory chain in isolated nerve
      terminals (synaptosomes) from neonatal and adult rats. Ischemia caused a
      significant, reversible decrease in mitochondrial Complex I activity in both
      adult and neonatal preparations. In neonatal preparations alone, ischemia also
      led to a significant decrease in mitochondrial Complexes II-III activity.
      Following 30 min of reperfusion mitochondrial Complexes II-III and IV exhibited
      decreased activity in synaptosomes from adult, but not neonatal rats. These data
      suggest a difference in the susceptibility of adult as compared to neonatal nerve
      terminal mitochondria to ischemia-reperfusion. These data show for the first time
      that nerve terminal mitochondria from immature animals remain undamaged following
      a period of ischemia and reperfusion, in contrast to nerve terminal mitochondria
      from the adult brain. This adds to the growing body of evidence that
      mitochondrial function plays a key role in neuronal death following cerebral
      ischemia reperfusion.

PMID- 10064797
TI  - Adrenocortical suppression blocks the enhancement of memory storage produced by
      exposure to psychological stress in rats.
AB  - Several reports have indicated that various stress stimuli modulate learning and
      memory processes. In the present study, the effects of adrenocortical suppression
      with the 11beta-hydroxylase inhibitor metyrapone on the psychological stress
      induced changes in memory storage in inhibitory avoidance training and in
      serotonin turnover in various brain regions were investigated in rats. Retention
      of one-trial inhibitory avoidance and the plasma corticosterone level were
      significantly enhanced by post-training exposure to psychological stress for 1 h.
      Pretreatment with metyrapone (12.5 or 25 mg/kg, s.c.) 90 min beforehand dose
      dependently blocked the enhancement of memory storage and of the plasma
      corticosterone level produced by psychological stress. These results suggest that
      the adrenocortical system may contribute to the memory-enhancing effect of
      psychological stress. In a neurochemical study, a significant increase in
      serotonin turnover in the hippocampus and limbic forebrain, including the nucleus
      accumbens, were observed in rats that were exposed to psychological stress. In
      contrast to the behavioral experiments, these changes in serotonin turnover
      produced by exposure to psychological stress were not antagonized by pretreatment
      with metyrapone; instead, a further increase in serotonin turnover was observed
      only in the hippocampus. These results suggest that the serotonergic system in
      the hippocampus might be selectively regulated by adrenal steroids in response to
      stress, and imply the existence of negative feedback mechanisms via a hippocampal
      serotonergic system in the memory enhancement associated with corticosterone and
      psychological stress.

PMID- 10064798
TI  - Small intensely fluorescent cells of the rat paracervical ganglion synthesize
      adrenaline, receive afferent innervation from postganglionic cholinergic
      neurones, and contain muscarinic receptors.
AB  - In the paracervical ganglion (PCG) of the rat, double-labelling
      immunofluorescence for catecholamine-synthesizing enzymes and HPLC measurement of
      catecholamine contents were first performed to evaluate whether intraganglionic
      small intensely fluorescent (SIF) cells are capable of synthesizing adrenaline.
      Immunolabelling for tyrosine hydroxylase (TH), dopamine beta-hydroxylase and
      phenylethanolamine-N-methyl transferase (PNMT) occurred in all SIF cells of the
      PCG, thus demonstrating the presence of all the enzymes required for adrenaline
      biosynthesis. Adrenaline levels were undetectable in the PCG but to test the
      hypothesis that PNMT is active in SIF cells, catecholamines were measured in
      ganglia of rats pretreated with pargyline, an inhibitor of the monoamine oxidase,
      the major enzyme involved in the catecholamine degradation. Pargyline treatment
      increased adrenaline levels in the PCG, thus demonstrating that SIF cells are
      capable of adrenaline synthesis. The undetectable levels of adrenaline in the PCG
      of untreated rats suggested a slow rate of biosynthesis of adrenaline in the
      ganglion. Furthermore, the use of double-labelling showed that SIF cells of the
      PCG were stained for muscarinic receptors and were approached by varicose ChAT
      immunoreactive nerve fibres. Nerve fibres immunoreactive for ChAT were also
      observed associated with nerve cell bodies of ganglion neurones. Following
      deafferentation of the PCG, the ChAT-immunoreactive nerve fibres surrounding
      nerve cell bodies totally disappeared indicating their preganglionic origin,
      while those associated with SIF cells did not degenerate, which demonstrate that
      they derived from intraganglionic cholinergic neurones. Taken together, the
      results show that adrenaline may be a transmitter for SIF cells in the PCG and
      suggest that cholinergic neurones of the parasympathetic division of the PCG can
      modulate the SIF cell activity through the activation of muscarinic receptors.

PMID- 10064799
TI  - Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor.
AB  - The main biological role of angiotensin II type 2 receptor (AT2) has not been
      established. We made use of targeted disruption of the mouse AT2 gene to examine
      the role of the AT2 receptor in the central nervous system (CNS). AT2-deficient
      mice displayed anxiety-like behavior compared with wild-type mice. However, AT2
      deficient mice showed no depressant-like activity and no change in hexobarbital
      induced sleeping time as compared with findings in wild-type mice. Both
      noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to
      be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I
      converting enzyme inhibitor), prazosin (alpha1 antagonist) reversed the anxiety
      like behavior in these AT2-deficient mice, whereas yohimbine (alpha2 antagonist),
      phenylephrine (alpha1 agonist), clonidine (alpha2 agonist), isoproterenol
      (beta1/beta2 agonist), propranolol (beta1/beta2 antagonist) and alpha-helical
      CRF9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like
      behavior in AT2-deficient mice. In addition, concentrations of plasma
      adrenocorticotropic hormone (ACTH) and corticosterone in AT2-deficient mice did
      not differ from these in wild-type mice, hence, there are probably no endocrine
      abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The
      amygdala appears to play an important role in many of the responses to fear and
      anxiety. The number of [3H]prazosin but not [125I]CRF binding sites in the
      amygdala was significantly reduced in AT2-deficient mice. These findings indicate
      that the noradrenergic system is involved in mediating the anxiety-like behavior
      in AT2-deficient mice.

PMID- 10064800
TI  - Functional reconstitution of a heteromeric cyclic nucleotide-gated channel of
      Caenorhabditis elegans in cultured cells.
AB  - The tax-4 and tax-2 genes of Caenorhabditis elegans are essential for normal
      olfaction, gustation, and thermosensation, suggesting that they have a role in
      sensory transduction. The predicted products of these genes are similar to the
      cyclic nucleotide-gated (CNG) channel subunits used in vertebrate vision and
      olfaction: TAX-4 is highly related to those alpha subunits, while TAX-2 is most
      closely related to the beta subunits of the rod phototransduction channels. TAX-4
      has previously been shown to form a highly sensitive cGMP-gated channel when
      expressed in human HEK293 cells. Here we show that TAX-4 and TAX-2 form a
      heteromeric channel when expressed in HEK293 cells, but TAX-2 does not form a
      channel on its own. Since these genes are expressed in the same neurons, most of
      the native channels in C. elegans are likely to be hetero-oligomers of TAX-4 and
      TAX-2 subunits, with TAX-4 as the alpha subunit and TAX-2 acting as a modifying
      beta subunit. The heteromeric TAX-4/TAX-2 channel is 25-fold less sensitive to
      cGMP than the TAX-4 channel, but it remains highly selective for cGMP over cAMP.
      The heteromeric channel and the TAX-4 homomeric channel differ in their blockage
      by divalent cations and in their single channel properties. These results suggest
      that cGMP is used as the second messenger during sensory signal transduction in
      C. elegans, and that distinct roles for alpha and beta subunits of CNG channels
      are conserved in vertebrate and invertebrate signal transduction.

PMID- 10064801
TI  - Functional activation of EphA5 receptor does not promote cell proliferation in
      the aberrant EphA5 expressing human glioblastoma U-118 MG cell line.
AB  - Eph receptors are a subfamily of receptor tyrosine kinases (RTKs), that are
      activated by ephrin ligands and appear to play important roles in axon guidance
      and cell migration during development of the nervous system. Over-expression or
      constitutive activation of Eph receptors has been linked with increased
      proliferation in various tumours. We have recently described lineage aberrant
      expression of EphA5 in primary human astrocytomas, glioblastomas and in the human
      glioblastoma U-118 MG cell line. A role for EphA5 expression in these tumours is
      not apparent, and we have investigated the cellular effects of EphA5 activation
      using the human glioblastoma U-118 MG cell line as a model. Immunofluorescent
      staining demonstrated cell surface expression of EphA5. Activation of the EphA5
      receptor using an ephrin-A1 recombinant fusion protein resulted in tyrosine
      phosphorylation of EphA5 in a time-dependent manner. Exposure of U-118 MG
      glioblastoma cells to ephrin-A1 did not result in significant spontaneous or FCS
      stimulated cell proliferation, though a marginal decrease was observed. This is
      in converse to the effects of Eph activation in other tumour cell lines, and is
      the first study to investigate EphA5 in glioblastoma cell lines.

PMID- 10064802
TI  - Phencyclidine induces D-1 dopamine receptor mediated Fos-like immunoreactivity in
      discretely localised populations of striatopallidal and striatoentopeduncular
      neurons in the rat.
AB  - Phencyclidine (PCP), a non-competitive antagonist of the NMDA subtype of
      glutamate receptor, which also acts as an indirect dopamine agonist and at sigma
      sites, can induce a long lasting psychotic state when taken acutely. It is well
      established that PCP is toxic to specific limbic structures and we have recently
      demonstrated that it induces apoptosis of a subpopulation of striatal neurons.
      These neurons lie predominantly in the dorsomedial striatum and project to the
      globus pallidus. The mechanisms mediating this neuronal death are unclear though
      manipulations of dopamine transmission can induce striatal c-fos expression and
      continuous c-fos expression has been implicated in the molecular cascades
      controlling apoptosis. We accordingly undertook a series of experiments to
      determine the action of PCP on striatal Fos-like immunoreactivity (FLI). PCP (80
      mg/kg, s.c.) elicited FLI in three distinct striatal areas, namely dorsomedial,
      dorsolateral and the nucleus accumbens. The level of PCP-induced FLI was
      consistently attenuated by the co-administration of the D-1 antagonist, SCH
      23390. Vehicle injections also induced modest levels of FLI in the dorsomedial
      striatum and the nucleus accumbens which again were attenuated by SCH 23390. The
      type of striatal neuron in which PCP-induced FLI was determined by the use of a
      retrograde anatomical tracer. A colloidal gold tracer was thus injected into the
      major areas of termination of striatal projection neurons prior to the
      administration of PCP. This procedure demonstrated that the majority of the FLI
      positive striatal cells were striatopallidal neurons, though some FLI positive
      striatoentopeduncular neurons were also seen. The potential pharmacological
      mechanisms underlying the results are discussed. It is argued that the complex
      pattern of PCP-induced striatal FLI might be accounted for by a differential
      action upon extracellular dopamine levels whereby they are elevated in some
      striatal areas and simultaneously reduced in others.

PMID- 10064803
TI  - Localization of oral-motor rhythmogenic circuits in the isolated rat brainstem
      preparation.
AB  - Using an in vitro isolated brainstem preparation from neonatal rat (0-2 days),
      the minimal circuitry for production of rhythmical oral-motor activity was
      determined. In the presence of the excitatory amino acid agonist, N-methyl-D,L
      aspartate (NMA), and the GABAA antagonist, bicuculline (BIC), rhythmical oral
      motor activity was recorded from the motor branch of the trigeminal nerve. In
      preparations where the brainstem was isolated in continuity between the rostral
      inferior colliculus and the obex, oral-motor activity was not observed. However,
      when the brainstem was serially transected in the coronal plane starting at the
      obex and proceeding rostrally, rhythmogenic activity emerged and became more
      stable until the level of the rostral facial nucleus (facial colliculus, FC) was
      approached. Transections more rostral than the FC produced rhythms that
      progressively deteriorated until the trigeminal motor nucleus (MoV) was reached,
      at which point all activities ceased. Surgical isolation of an ipsilateral
      quadrant of the brainstem encompassing the tissue between the FC and inferior
      colliculus, rostro-caudally, and the midline to lateral brainstem, medio
      laterally, exhibited oral-motor activity as well. The remaining contralateral
      side of brainstem was devoid of rhythmical trigeminal activity. However, further
      coronal transection of the remaining brainstem at the level of the FC induced
      rhythmical oral-motor activity in the trigeminal nerve. The data suggest the
      existence of bilaterally coordinated rhythmogenic circuits in each half of
      brainstem between the rostral trigeminal nucleus and the rostral facial nucleus,
      which are tonically inhibited by brainstem circuits caudal to the facial nucleus.

PMID- 10064804
TI  - Alpha2A-adrenergic receptors are primarily presynaptic heteroreceptors in the C1
      area of the rat rostral ventrolateral medulla.
AB  - The 2A subtype of the alpha-adrenergic receptor (alpha2A-AR) is necessary for the
      hypotensive effects of clonidine and other sympathoinhibitory adrenergic
      agonists. This hypotensive response appears to be due to the inhibition of
      sympathoexcitatory reticulospinal neurons found in the rostral ventrolateral
      medulla (RVL), including neurons of the C1 adrenergic cell group. The cellular
      mechanisms underlying this inhibition have not been established. Thus, this study
      examined the ultrastructural relationships between profiles containing alpha2AAR
      immunoreactivity (alpha2AAR-I) and those containing the catecholamine
      synthesizing enzyme tyrosine hydroxylase (TH) to determine potential cellular
      substrates for alpha2A-AR inhibition of C1 neuron activity. Consistent with
      previous light microscopic studies, alpha2AAR-I was found in perikarya and large
      dendrites and the majority of these profiles also contained TH-labeling
      (approximately 70% of 140). However, alpha2AAR-I in these cells was primarily
      found within endosomes and Golgi complexes and in clusters associated with the
      endoplasmic reticula, probable sites for synthesis and/or trafficking of
      receptors. In contrast, most of the alpha2AAR-I profiles (n=646) in the RVL were
      axons and axon terminals (approximately 68%) which lacked TH immunoreactivity.
      alpha2AAR-labeled axons were small and unmyelinated and labeled terminals usually
      formed symmetric synapses on the shafts of catecholaminergic or unlabeled
      dendrites. Most of these alpha2AAR-labeled axons were found in close proximity to
      TH-labeled profiles and approximately one-fifth (17% of 408) of the alpha2AAR
      labeled axons and axon terminals directly contacted TH-labeled profiles, mostly
      dendrites. These studies suggest that alpha2AARs in the C1 area of the RVL
      function primarily as heteroreceptors on presynaptic axons and terminals of non
      catecholaminergic cells, some of which provide inhibitory synaptic input to C1
      neurons. These receptors may be activated by catecholamines released either from
      the dendrites of C1 neurons or from the terminals of other catecholaminergic
      neurons via volume transmission.

PMID- 10064805
TI  - Non-uniform expression of alpha subunit isoforms of the Na+/K+ pump in rat dorsal
      root ganglia neurons.
AB  - Tissue sections and antibodies selectively recognizing isoforms of the alpha
      subunit of the Na+/K+ pump were used to determine the expression of alpha1,
      alpha2 and alpha3 pump isoforms in the plasma membrane of adult rat dorsal root
      ganglia (DRG) neurons. There was no detectable membrane signal from DRG neurons
      that were probed with antibodies to the alpha2 isoform of the Na+/K+ pump. The
      alpha1 isoform of the Na+/K+ pump was found in most (77+/-4%) studied DRG
      neurons, regardless of cell size. Only 16+/-7% of the neurons expressed a
      detectable level of the alpha3 Na+/K+ pump and all were apparently from a
      subpopulation of large DRG neurons. Comparison of cell size distributions and a
      study of neurons identified in serial sections suggested that of the alpha3
      positive DRG neurons about 75% coexpressed the alpha1 isoform of the Na+/K+ pump.
      These data show that the expression of the protein of the alpha subunit isoforms
      of the Na+/K+ pump is not uniform throughout the population of DRG neurons and
      that alpha1 is the predominant isoform in the plasma membrane of these neurons.

PMID- 10064806
TI  - Chronic (-) deprenyl administration alters dendritic morphology of layer III
      pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys.
AB  - Chronic (-) deprenyl (0.2 mg/kg, b.wt; for 25 days) treatment induced alterations
      in the dendritic morphology of prefrontal cortical neurons in adult Bonnett
      monkeys were evaluated in the present study. The branching points and
      intersections in apical and basal dendrites were studied up to a distance of 400
      and 200 micrometers, respectively, in Golgi impregnated layer III pyramidal
      neurons of the prefrontal cortex. Our results revealed a significant (p<0.001)
      increase in the number of branching points and intersections in both apical and
      basal dendrites in (-) deprenyl treated monkeys compared to controls. Such an
      enriched dendritic arborization in prefrontal cortical neurons may be responsible
      for the enhancement of cognitive functions in Alzheimer disease patients
      following (-) deprenyl treatment.

PMID- 10064807
TI  - Morphine antinociception elicited from the ventrolateral periaqueductal gray is
      sensitive to sex and gonadectomy differences in rats.
AB  - Sex differences have been observed in antinociception following central
      administration of morphine into either the lateral ventricles or rostral
      ventromedial medulla (RVM) such that male rats exhibit significantly greater
      antinociception than female rats. The present study examined whether sex and
      adult gonadectomy differences were observed in morphine-induced (1-10 micrograms)
      antinociception elicited from the ventrolateral periaqueductal gray (vlPAG) on
      two nociceptive measures. Both sham-operated (ED50=1.20-1.60 microgram) and
      castrated (ED50=1.08-1.09 micrograms) male rats displayed significantly greater
      magnitudes and potencies of morphine-induced antinociception on both tests than
      female rats. Sham-operated female rats tested during the estrous phase (ED50=>50
      micrograms) were significantly less sensitive to morphine than ovariectomized
      female rats (ED50=1.98-2. 51 micrograms). Thus, the vlPAG, a site sensitive to
      interactions between estradiol-containing hypothalamic loci and opioid peptides,
      elicits morphine-induced antinociception which is sensitive to sex differences
      and adult gonadectomy.

PMID- 10064808
TI  - Peptide 19 in the dorsal root ganglion and the mesencephalic trigeminal tract
      nucleus of the adult rat.
AB  - Peptide 19-immunoreactivity (PEP 19-ir) was examined in the dorsal root ganglion
      (DRG) and the mesencephalic trigeminal tract nucleus (Mes5) of the adult rat.
      Thirty-eight percent of DRG cells were immunoreactive (ir) for PEP 19. These
      neurons were small to large and measured 167-4583 micron2 (mean+/-S.D.=2048+/-913
      micron2). Seventy-five percent of DRG cells >2000 micron2 and 15% of those <1000
      micron2 exhibited PEP 19-ir. Thirty-six percent of DRG neurons in the range 1000
      2000 micron2 showed the ir. In the Mes5, 87% of primary neurons were ir for this
      peptide. Muscle spindles in the soleus and masseter muscles contained PEP 19-ir
      spiral axon terminals. Double immunofluorescence methods revealed the co
      expression of PEP 19 and calcium binding proteins. Eighty-six percent of
      parvalbumin-ir neurons exhibited PEP 19-ir. Conversely, 60% of PEP 19-ir neurons
      showed parvalbumin-ir. The cell size analysis revealed that 55% of PEP 19-ir
      neurons >600 micron2 showed parvalbumin-ir and that all PEP 19-ir neurons <600
      micron2 were devoid of it. Ninety percent of PEP 19-ir DRG neurons showed S100
      ir, whereas 60% of S100-ir ones co-expressed PEP 19-ir. In the Mes5, virtually
      all PEP 19-ir primary neurons exhibited parvalbumin-ir. The co-expression of PEP
      19 and S100 could not be observed in the nucleus. The present study indicates
      that PEP 19-ir neurons which co-express parvalbumin-ir are proprioceptors in the
      spinal and the trigeminal systems. PEP 19-ir small DRG neurons without S100-ir
      are probably exteroceptors and may include unmyelinated nociceptors.

PMID- 10064809
TI  - Neurochemical evidence for inflammation-induced activation of the coeruleospinal
      modulation system in the rat.
AB  - By using the microdialysis technique, the concentration of noradrenaline (NA) in
      the dorsal horn during unilateral hindpaw inflammation was compared between rats
      receiving bilateral lesions of the locus coeruleus (LC) and non-operated control
      rats. Bilateral lesions of the LC were made using an anodal current one week
      before testing. Unilateral hindpaw inflammation was produced by a subcutaneous
      injection of carrageenan (6 mg in 0.15 ml saline). Under conditions of sodium
      pentobarbital anesthesia, the microdialysis probe was inserted into the dorsal
      horn either ipsilateral or contralateral to the site of inflammation. The NA
      concentration in the dialysate was measured by high-performance liquid
      chromatography with electrochemical detection. Prior to carrageenan injection,
      the NA level (baseline level) did not differ between the LC-lesioned and the non
      operated groups. After carrageenan injection, in the non-operated rats, the NA
      level increased significantly compared to the baseline level only in the dorsal
      horn ipsilateral to the site of inflammation, but not in the dorsal horn
      contralateral to the site of inflammation. An increase of the NA level was not
      observed in the LC-lesioned rats and in rats receiving an injection of saline.
      The result suggests that unilateral hindpaw inflammation produces excitation of
      descending NA-containing neurons from the LC, resulting in an increase of the NA
      level in the dorsal horn ipsilateral to the site of inflammation.

PMID- 10064810
TI  - Hippocampal microtubule-associated protein-2 alterations with contextual memory.
AB  - Using immunohistochemistry and immunoblots, we show that alterations in
      hippocampal microtubule-associated protein-2 appear to be highly correlated with
      contextual memory as measured by significantly heightened fear responses.
      Compared to naive controls, rats trained in a novel context showed significantly
      increased immunostaining for the high molecular weight microtubule-associated
      protein-2a/b. This increase was observed 2 weeks after training and it was
      selective for hippocampal CA1 and CA2 pyramidal cells. Pre-exposure to the
      training context one month before training altered the hippocampal microtubule
      associated protein-2 response; in these animals only the dentate gyrus showed
      significantly increased microtubule-associated protein-2a/b. Training-related
      increases in immunohistochemical staining for microtubule-associated protein-2
      suggested that there was an increase in overall intact protein, an increase in
      immunoreactive breakdown products, or changes in protein compartmentalization.
      Immunoblots of hippocampal homogenates reacted with monoclonal antibodies to
      microtubule-associated protein-2a/b showed an increased presence of breakdown
      products in trained animals compared to untrained controls. Additional immunoblot
      studies demonstrated statistically significant decreases in the levels and/or
      phosphorylation state of the low molecular weight microtubule-associated protein
      2c in the hippocampus of trained animals as compared to that of controls. These
      alterations in microtubule-associated protein-2 may reflect dendritic remodeling
      related to contextual memory storage.

PMID- 10064811
TI  - A subpopulation of neurons in the rat rostral nucleus of the solitary tract that
      project to the parabrachial nucleus express glutamate-like immunoreactivity.
AB  - In rodents, gustatory information is transmitted from second order neurons in the
      rostral nucleus of the solitary tract (rNST) to the parabrachial nucleus (PBN) in
      the pons. The chemical nature of this projection is unknown. Therefore, the goal
      of the current study was to determine if rNST neurons that project to the PBN
      express glutamate-like immunoreactivity. Projection neurons were retrogradely
      labeled following stereotaxic injection of rhodamine-filled latex microspheres
      into the right PBN of seven rats while glutamate-immunoreactive (GLU-IR)
      structures were visualized in the same tissue using an immunoperoxidase
      procedure. The number of single- and double-labeled neurons located in the right
      (ipsilateral) and left rNST, in each of the nuclear subdivisions as well as their
      position along the rostral-caudal axis of the rNST was determined. GLU-IR cell
      bodies were located throughout the rNST. Although the rostral central subdivision
      contained the highest percentage (33.8%) of GLU-IR perikarya, immunolabeled
      neurons were most concentrated (number/area of subdivision) within the medial
      subnucleus. The rostral third of the rNST contained the fewest (20. 5%) and
      lowest density of GLU-IR cell bodies. The highest percentage of rNST neurons
      retrogradely labeled from the PBN were located ipsilateral (85.4%) to the pontine
      injection site, in the middle third of the nucleus (44.2%) and within the rostral
      central subdivision (52.4%). Overall, 18% of the labeled rNST projection neurons
      were GLU-IR. The distribution of double-labeled neurons mirrored that of the
      projection neurons with the largest number located in the ipsilateral rNST
      (84.5%), middle third of the nucleus (40.5%) and rostral central subdivision
      (64.7%). These results indicate that glutamate may be a main component of the
      ascending pathway from the rNST to the PBN. In addition, since GLU-IR neurons
      were located throughout the rNST and most were not retrogradely-labeled, the
      current results suggest that glutamate may be an important neurotrans-mitter
      within the medulla.

PMID- 10064812
TI  - Increased NPY activity in the PVN contributes to food-restriction induced
      reductions in blood pressure in aortic coarctation hypertensive rats.
AB  - We hypothesized that hypothalamic NPYergic mechanisms mediate the blood pressure
      lowering effect of caloric restriction in hypertensive rats. Aortic coarctation
      induced (AC) hypertensive rats (n=25) were assigned to either an ad libitum fed
      control group (AL) or food restricted group (FR; 60% of AL consumption) for 3
      weeks. Rats were instrumented chronically with vascular catheters and bilateral
      guide cannulae directed at the paraventricular hypothalamic nuclei (PVN). Blood
      pressure (BP) and heart rate (HR) responses to bilateral PVN microinjection of
      saline (200 nl) or the putative NPY receptor antagonists [D-Trp32]NPY(1-36) (3.3
      micrograms/200 nl) and [D-Tyr27,36 Thr32]NPY(27-36) (D-NPY(27-36); 3.3
      micrograms/200 nl) were determined. The FR rats were then refed and
      cardiovascular responses to PVN injections of NPY receptor antagonists were again
      determined. FR rats had significantly reduced resting BP (159+/-4 vs. 129+/-4
      mmHg) and HR (360+/-11 vs. 326+/-9 bpm) compared to AL controls. Refeeding
      restored BP and HR of FR rats to levels similar to AL (BP=153+/-4 mmHg, HR=359+/
      11 bpm). PVN administration of [D-Trp32]NPY produced foraging behavior and
      concurrent increases in BP and HR in FR, AL and Re-fed rats. The behavioral
      activation suggests that [D-Trp32]NPY(1-36) produced activation of NPY receptors.
      In contrast, D-NPY (27-36) did not produce any behavioral response or affect BP
      or HR in AL or Re-fed rats. In FR rats, D-NPY (27-36) produced significant
      increases in BP (peak=15+/-3 mmHg) which partially reversed the effect of FR on
      BP. Thus, in FR rats with reduced BP, PVN administration of an NPY receptor
      antagonist increases BP. NPY blockade in the PVN accounted for about 50% of the
      BP effect of food restriction, thus other mechanisms are likely to be involved.
      These findings are consistent with the hypothesis that NPYergic mechanisms may
      contribute to the reduction of BP produced by food restriction.

PMID- 10064813
TI  - Expression of galanin immunoreactivity in gonadotropin-releasing hormone neurons
      in mice: a confocal microscopic study.
AB  - The expression of galanin immunoreactivity (galanin-IR) in gonadotropin-releasing
      hormone (GnRH) neurons was investigated in mice using double label
      immunohistochemistry combined with confocal laser scanning microscopy. A large
      proportion of GnRH cells in proestrous mice and very few GnRH cells in male mice
      exhibited galanin-IR. These results are consistent with earlier reports in rats.
      Unlike in rats, the proportion of GnRH cells coexpressing galanin in mice was
      high following ovariectomy (OVX) and the treatment of OVX mice with estrogen
      decreased the number of GnRH cells with galanin-IR. The GnRH system can be
      considered more active during proestrous and following OVX since the output of
      luteinizing hormone is elevated during these phases in females. Since the
      induction of galanin-IR in GnRH cells is more pronounced in OVX and proestrous
      mice, the expression of galanin-IR in GnRH cells in mice appears to be an
      activation-dependent phenomenon rather than a direct effect of estrogen. However,
      in OVX mice treated with steroids to induce an LH surge the number of GnRH cells
      with galanin-IR was not proportionately increased. The possible reasons for this
      discrepancy are also discussed.

PMID- 10064814
TI  - Alterations in spontaneous single unit activity of striatal subdivisions during
      ontogenesis in mutant dystonic hamsters.
AB  - The pathophysiology of idiopathic dystonia, characterized by sustained twisting
      movements and postures, is still unknown. Clinically, however, the basal ganglia
      are thought to be the main causative origin of idiopathic dystonia. In the dtsz
      hamster, a genetic animal model for idiopathic paroxysmal dystonia, the attacks
      occur in response to mild stress and the severity of dystonia is age-dependent.
      Previous autoradiographic studies in the dtsz hamster revealed a decreased
      dopamine D1 and D2 receptor binding and an increased [3H]-2-deoxyglucose uptake
      in the dorsomedial caudate-putamen (CPu), a region supposed to be critically
      involved in dystonia. Therefore, we were interested whether the spontaneous
      firing rate of dorsomedial striatal neurons is age-dependently altered in
      comparison to age-matched non-dystonic control hamsters. Extracellular recordings
      of spontaneous single unit activity of dorsomedial and ventromedial Type II
      striatal neurons, i.e., biphasic positive-negative action potentials, from
      fentanyl anesthetized animals revealed a drastically increased firing rate in the
      dorsomedial CPu of mutants during age of maximum severity of dystonia. In post
      dystonic dtsz hamsters, i.e., after remission of stress-inducible dystonia, no
      significant differences regarding the dorsomedial CPu could be obtained. We
      conclude that the dorsomedial subregion of the CPu seems to be critically
      involved in the dystonic syndrome of dtsz hamsters and that a transiently reduced
      inhibitory control over excitatory cortico-striatal processes, possibly due to an
      altered development of GABAergic inhibition, occurs during ontogenesis in dtsz
      hamsters.

PMID- 10064815
TI  - Mu opioids enhance mossy fiber synaptic transmission indirectly by reducing GABAB
      receptor activation.
AB  - The cellular mechanisms underlying mu opioid facilitation of mossy fiber (MF)
      long-term potentiation (LTP) and synaptic transmission were investigated in the
      rat hippocampal slice. Naloxone (10 microM) significantly inhibited the induction
      of mossy fiber LTP, an effect attributed by Derrick and Martinez [B.E. Derrick,
      J.L.J. Martinez, Opioid receptor activation is one factor underlying the
      frequency dependence of mossy fiber LTP induction, J. Neurosci. 14 (1994) 4359
      4367] to antagonism of endogenous opioid peptide action. We found that the
      inhibitory effects of naloxone were not blocked by bicuculline, suggesting that
      endogenous opioids did not enhance mossy fiber LTP by depressing GABAA
      inhibition. [d-Ala2, NMePhe4, Glyol5] enkephalin, DAMGO (300 nM), a mu opioid
      agonist, mimicked the action of endogenous opioids, enhancing both mossy fiber
      LTP induction and paired-pulse facilitation. DAMGO potentiation of the paired
      pulse facilitation of mossy fiber response was also insensitive to bicuculline
      but was blocked by the mu selective antagonist CTOP. Further analysis of the
      cellular mechanism showed that the depletion of internal Ca2+ stores by
      thapsigargin (1 microM), or inhibition of protein kinases by application of
      staurosporine (1 microM) did not block the DAMGO facilitation of mossy fiber-CA3
      synaptic transmission. However, application of phaclofen (100 microM GABAB
      receptor antagonist or SCH 50911, a more potent GABAB antagonist significantly
      inhibited the DAMGO effect (49+/-15%; 51+/-19% inhibition, P<0.05). The data
      indicate that the DAMGO effect on the mossy fiber pathway is partially mediated
      by a reduction in GABA activation of GABAB receptors. These findings further
      suggest that endogenous opioid peptides activate mu opioid receptors to
      facilitate mossy fiber LTP and synaptic transmission in rat hippocampus partially
      by GABAB receptor-mediated disinhibitory mechanism.

PMID- 10064816
TI  - Structure-activity relationships of the Helix neuropeptide, SEPYLRFamide, and its
      N-terminally modified analogues on identified Helix lucorum neurones.
AB  - Metabotropic and ionotropic effects evoked by the endogenous Helix heptapeptide,
      SEPYLRFamide, and four analogues, i.e., where the amino acid sequences at the N
      terminal (EPYLRFamide, SEGYLRFamide, SRPYLRFamide and SKPYLRFamide) were
      modified, were compared on identified Helix lucorum LPa2, LPa3, RPa3, RPa2
      neurones using two electrode voltage clamp and current clamp techniques. All
      peptides (bath application) reduce reversibly the inward current to local
      ionophoretic application of acetylcholine onto the neurone soma with an order of
      potency: EPYLRFamide=SEGYLRFamide=SRPYLRFamide>SEPYLRFamide+ ++>SKPYLRFamide. The
      reductions of the acetylcholine-induced inward current evoked by SEPYLRFamide and
      its analogues at concentrations of 0.01-10 microM are not accompanied by a change
      of amplitude of the leak inward current caused by constant negative shift of a
      holding potential. At concentration of 50 microM all peptides increase reversibly
      the resting membrane conductance to an equal degree. Local application under
      pressure of SEPYLRFamide and its analogues onto the soma of neurones evoke
      hyperpolarizations with similar values. These results indicate that the N
      terminal three amino acids of the peptide molecule are not responsible for the
      degree of ionotropic effect on the neurones studied. In contrast the amino acid
      sequence at the N-terminal modifies the degree of the modulatory effects of the
      YLRFamide-related analogues. Changes at the SEPYLRFamide N-terminal (Ser1-Glu2
      Pro3) intensify the inhibitory action of the analogues as compared with effect
      evoked by the endogenous peptide, that is, removal of Ser1 (Glu1-Pro2),
      replacement of Pro3 with Gly3 (Ser1-Glu2-Gly3), replacement of Glu2 with Arg2
      (Ser1-Arg2-Pro3). Replacement of Glu2 with Lys2 (Ser1-Lys2-Pro3) reduces the
      modulatory potency. It is concluded that ionotropic and metabotropic effects of
      these YLRFamide-related peptides may occur at different membrane binding sites.

PMID- 10064817
TI  - Sex differentiation of growth hormone-releasing hormone and somatostatin neurons
      in the mouse hypothalamus: an immunohistochemical and morphological study.
AB  - We examine sexual dimorphism in growth hormone-releasing hormone (GHRH) in the
      arcuate nucleus (ARC), and somatostatin (SS) in the periventricular nucleus (PeN)
      of the hypothalamus, and investigate when it becomes evident. Using
      immunohistochemical staining and morphometry, we observed ARC GHRH-immunoreactive
      (ir) neurons, ARC SS-ir neurons and PeN SS-ir neurons in male and female mice at
      5, 20, 30, 40 and 60 days old. The number of ARC GHRH-ir neurons was
      significantly higher in males than females, after 20 days old. ARC SS-ir neurons
      showed no significant differences between sexes. On the other hand, PeN SS-ir
      neurons were significantly more numerous in males at 30, 40 and 60 days than in
      females. During postnatal development, these GHRH- and SS-ir neurons changed in
      different patterns from ages 20 to 60 days. The number of ARC GHRH-ir neurons in
      both sexes decreased from 5 to 20 days, increased until day 40, and then
      decreased at day 60, while ARC SS-ir neurons in both sexes increased from day 5
      to day 60. PeN SS-ir neurons in both sexes increased from days 5 to 20 to 116% in
      males and 189% in females. Furthermore, in male mice, the increase continued
      until 40 days of age, while in females, there was no significant difference from
      days 20 to 60. There were no apoptotic cells; a few proliferating cell nuclear
      antigen (PCNA) stained cells were found in the ARC and PeN. Our results suggest
      that the sex difference of ARC GHRH neurons and PeN SS neurons appears by
      stimulation with testosterone during the development life. The developmental
      fluctuation in the number of ARC GHRH-ir neurons may not be modulated by
      testosterone, but by ARC SS neurons.

PMID- 10064818
TI  - Distinct distribution and time-course changes in neuronal nitric oxide synthase
      and inducible NOS in the paraventricular nucleus following lipopolysaccharide
      injection.
AB  - Nitric oxide (NO) is known to be involved in the modulation of neuroendocrine
      function. To clarify the role of different isoforms of NO synthase (NOS) in the
      neuroendocrine response to immune challenge, the expressions of neuronal NOS
      (nNOS) and inducible NOS (iNOS) genes in the hypothalamus following
      lipopolysaccharide (LPS) injection were examined using in situ hybridization. NOS
      activity was also determined by NADPH-diaphorase (NADPH-d) histochemistry. LPS
      (25 mg/kg) or sterile saline was injected intraperitoneally to male Wistar rats
      and the rats sacrificed 30 min, or 1, 2, 3, 5, 12 or 24 h after injection. nNOS
      mRNA expression in the paraventricular nucleus (PVN) was significantly increased
      2 h after LPS injection. iNOS mRNA, which was not detected until 2 h after LPS
      injection, was significantly increased in the PVN 3 h after LPS injection. Both
      RNA expressions had returned to basal levels by 12 h after LPS injection. The
      number of NADPH-d positive cells was significantly increased 5 h after LPS
      injection. iNOS expression was more robust in parvocellular PVN, while nNOS was
      distributed mainly in the magnocellular PVN. Double in situ hybridization
      histochemistry revealed that some of the iNOS- (48.4%) or nNOS-positive cells
      (34. 3%) in the parvocellular PVN expressed CRF mRNA. The results demonstrate
      that LPS-induced sepsis causes significant increases in nNOS and iNOS gene
      expression with different time-courses and distributions, and that iNOS mRNA was
      more frequently co-localized with CRF-producing parvocellular neurons in the PVN.
      Thus, NO produced by iNOS and nNOS may play an important role in the
      neuroendocrine response to an immune challenge. Distinct differences in the
      distribution and time-course changes of iNOS and nNOS suggest different roles for
      the hypothalamic-pituitary-adrenal axis and/or neurohypophyseal system.

PMID- 10064819
TI  - Cellular localization of the heat shock transcription factors HSF1 and HSF2 in
      the rat brain during postnatal development and following hyperthermia.
AB  - The heat shock transcription factor HSF1 mediates the induction of heat shock
      genes in response to temperature elevation and other traumatic events. The
      induced hsps play roles in cellular repair and protective mechanisms.
      Immunocytochemistry revealed that in the unstressed rat, HSF1 was already
      prepositioned in the nucleus at abundant levels in both neuronal and glial cell
      types. Following a fever-like temperature, glial cells rapidly induced hsp70
      whereas populations of large neurons did not. The lack of hsp70 induction in
      these neurons in vivo did not appear to be due to deficiencies in levels of
      nuclear HSF1. During postnatal development of the cerebellum, levels of HSF1
      increased progressively from day 1 to 30. Members of the hsp gene set are also
      constitutively expressed in the unstressed animal and play roles as molecular
      chaperones. HSF2, which has been proposed as a developmental regulator of
      constitutive heat shock gene expression, demonstrated a developmental alteration
      in cellular localization, namely a nuclear distribution in neurons at postnatal
      day 2 and a cytoplasmic localization at day 30. During postnatal development the
      overall levels of neural HSF2 declined. This profile showed no obvious
      correlation with previously observed levels of constitutive hsp expression during
      postnatal neural development.

PMID- 10064820
TI  - Cellular localization of brain-derived neurotrophic factor-like immunoreactivity
      in adult monkey brain.
AB  - Immunohistochemical localization of brain-derived neurotrophic factor (BDNF) in
      the monkey brain was investigated using a polyclonal anti-BDNF antibody produced
      in our laboratory. The antibody recognized a single band in monkey brain
      homogenates, and the estimated molecular weight was approximately 14 kDa, which
      corresponds well to the molecular weight of BDNF monomer. BDNF-like
      immunoreactivity was observed in the somata and processes of discrete neuronal
      subpopulations in the monkey brain. BDNF-positive neurons were widely distributed
      in various structures of the brain, including the cerebral cortex, hippocampus,
      basal forebrain, basal ganglia, diencephalon, brainstem and cerebellum. In
      addition, immunopositive glial cells were found in some brain regions. These data
      suggest that BDNF may exist widely in the monkey brain, and may be concerned with
      various types of neurons in the monkey central nervous system.

PMID- 10064821
TI  - Differential basal proenkephalin gene expression in dorsal striatum and nucleus
      accumbens, and vulnerability to morphine self-administration in Fischer 344 and
      Lewis rats.
AB  - We have previously shown that the acquisition rate of intravenous morphine self
      administration under a fixed ratio one (FR1) schedule of reinforcement was
      greater in Lewis (LEW) than Fischer 344 (F344) rats. The purpose of the present
      experiment was to examine the relative motivational properties of morphine (1
      mg/kg) or food under progressive ratio (PR) schedules of reinforcement in LEW and
      F344 rats. In addition, by using in situ hybridization histochemistry we have
      measured in both strains of rats the basal level of proenkephalin (PENK) gene
      expression in dorsal striatum and nucleus accumbens (NAcc). The results show that
      LEW rats responded to significantly higher breaking points (BPs) than F344 rats
      for intravenous morphine self-administration. In contrast, no differences were
      found in BPs for food pellets. Basal PENK mRNA levels were significantly higher
      in the dorsal striatum and nucleus accumbens of F344 than in LEW rats. Taken
      together, these results reveal a strain difference in the reinforcing efficacy of
      morphine and in the basal PENK gene expression in brain regions involved in the
      reinforcing actions of opiates. These data also suggest that the strain
      differences in opiate self-administration behavior found in this and other
      studies may be related, at least in part, to differences in basal opioid activity
      between LEW and F344 rats.

PMID- 10064822
TI  - The expression of mRNAs for hepatocyte growth factor/scatter factor, its receptor
      c-met, and one of its activators tissue-type plasminogen activator show a
      systematic relationship in the developing and adult cerebral cortex and
      hippocampus.
AB  - The temporal and spatial expression in brain of the mRNAs for the pleiotropic
      cytokine hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-met
      were compared to those of a known HGF/SF activator, tissue-type plasminogen
      activator (tPA). In addition to the previously described expression in the
      developing and adult olfactory system [D.P. Thewke, N.W. Seeds, Expression of
      hepatocyte growth factor/scatter factor, its receptor, c-met, and tissue-type
      plasminogen activator during development of the murine olfactory system, J.
      Neurosci. 16 (1996) 6933-6944] two other regions of the mouse brain were found
      where the expression of tPA mRNA appeared to co-localized with HGF/SF and/or c
      met mRNA. In the developing hippocampus, tPA mRNA was expressed coincident with
      HGF/SF and c-met mRNAs in the CA1 field. tPA mRNA was expressed in all areas of
      the adult hippocampus, while HGF/SF expression was restricted to the CA2 and CA3
      fields, and c-met mRNA was seen primarily in the CA1 field. In the developing
      cerebral cortex, the expression of tPA mRNA was observed in the subplate and
      inner cortical plate between two layers of c-met expression, whereas HGF/SF mRNA
      was localized to the proliferative zone lining the lateral ventricle. Layer
      specific expression of both HGF/SF and c-met mRNA were observed in the adult
      cortex, where HGF/SF was expressed in layers IV and V and c-met in layers II-III,
      IV and V. The expression of tPA mRNA in the adult cortex was low and not layer
      specific, although homogenates of adult cortex did have detectable levels of tPA
      activity when subjected to zymography. Immunohistochemical analysis using HGF/SF
      and c-met antibodies on adult brain sections showed a distribution similar to the
      in situ hybridization results. C-met antibodies appeared to stain large neurons
      in the cortex and hippocampus. These results are consistent with the hypothesis
      that HGF/SF plays a role in the development and maintenance of both the cerebral
      cortex and hippocampus, and that tPA may act as a regulator of HGF/SF activity in
      these structures.

PMID- 10064823
TI  - Role of soluble guanylate cyclase in dilator responses of the cerebral
      microcirculation.
AB  - Responses of cerebral blood vessels to nitric oxide (NO) are mediated by soluble
      guanylate cyclase (sGC)-dependent and potentially by sGC-independent mechanisms.
      One sGC-independent mechanism by which NO may produce vasodilatation is
      inhibition of formation of a vasoconstrictor metabolite produced through the
      cytochrome P450 pathway. In these experiments, we examined the hypothesis that
      dilatation of cerebral microvessels in response to NO is dependent on activation
      of sGC. Diameters of cerebral arterioles (baseline diameter=94+/-5 micrometers,
      mean+/-S.E.) were measured using a closed cranial window in anesthetized rabbits.
      Under control conditions, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole],
      an NO-independent activator of sGC, produced vasodilation that was blocked by ODQ
      (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one)(10 microM), an inhibitor of sGC.
      These findings indicate that sGC is functionally important in cerebral
      arterioles. In addition, acetylcholine (which stimulates endogenous production of
      NO by endothelium) produced dilatation of cerebral arterioles that was inhibited
      by ODQ. For example, 1 microM acetylcholine dilated cerebral arterioles by 34+/-7
      and 5+/-1% in the absence and presence of ODQ (10 microM), respectively.
      Increases in arteriolar diameter in response to sodium nitroprusside (1 microM,
      an NO donor) were inhibited by approximately 80% by ODQ, but were not affected by
      17-ODYA (10 microM) or clotrimazole (10 microM), inhibitors of the cytochrome
      P450 pathway. Thus, dilatation of the cerebral microcirculation in response to
      exogenously applied and endogenously produced NO is dependent, in large part, on
      activation of sGC.

PMID- 10064824
TI  - NS-257, a novel competitive AMPA receptor antagonist, interacts with kainate and
      NMDA receptors.
AB  - In this study, we examined the effects of a novel, water-soluble, putative
      competitive AMPA receptor antagonist, 1,2,3,6,7, 8-hexahydro-3-(hydroxyimino)
      N,N,7-trimethyl-2-oxobenzo[2,1- b:3, 4-c']dipyrrole-5-sulfonamide (NS-257) on
      AMPA, kainate and NMDA receptors using the two-electrode voltage-clamp technique
      in Xenopus oocytes. All glutamate receptor subtypes were inhibited by NS-257 in a
      voltage-independent way. When kainate was applied to oocytes injected with total
      mouse brain mRNA, mainly AMPA receptors were activated. The antagonistic effects
      of NS-257 on these kainate-induced currents were concentration-dependent and
      competitive. In the same way, NS-257 blocked kainate-induced currents recorded
      from oocytes expressing homomeric GluR-1 receptors. In our experiments higher
      concentrations (>1 microM) of NS-257 also produced inhibitory effects on kainate
      and to a lesser extent on NMDA receptor function as indicated by recordings from
      GluR-6 or NR-1b/2A cRNA injected oocytes. While NMDA receptor function was
      inhibited in a competitive fashion, kainate responses recorded from homomeric
      GluR-6 receptors were blocked in a mixed competitive-noncompetitive manner. This
      mixed antagonistic action of NS-257 might have been caused by preincubating
      oocytes with concanavalin A, which blocks desensitization of kainate receptors.
      Although NS-257 appeared to be a less potent AMPA receptor antagonist then other
      known antagonists like NBQX, its main advantage over all other reported compounds
      so far is its higher aqueous solubility which still represents the major weakness
      of the other AMPA receptor antagonists, especially for clinical use.

PMID- 10064825
TI  - Relations of hippocampal volume and dentate gyrus width to gonadal hormone levels
      in male and female meadow voles.
AB  - The present study examined hippocampal volume and dentate gyrus width and their
      relations to gonadal hormone levels in adult male and female meadow voles,
      Microtus pennsylvanicus. Females were split into High and Low Estradiol groups
      based on the median estradiol level. Males were similarly split into High and Low
      Testosterone groups. Contrary to previous reports in wild meadow voles, there was
      no evidence of an overall sex difference in hippocampal volume. However, when
      male-female comparisons were limited to High Testosterone males and Low Estradiol
      females a significant sex difference in hippocampal volume favouring males did
      emerge. Hippocampal volume in males was related to testosterone level, with High
      Testosterone males having significantly larger hippocampi than Low Testosterone
      males. Similarly, there was a significant influence of plasma estradiol level on
      hippocampal volume and left dentate gyrus width, with High Estradiol females
      having larger hippocampi and dentate gyrus width than Low Estradiol females. In
      addition, consistent with previous findings in the laboratory rat, there were sex
      differences favouring males in right dentate gyrus width. These findings show
      that there is a complex relationship between hippocampal volume, dentate gyrus
      width and gonadal hormone levels in male and female meadow voles.

PMID- 10064826
TI  - Modulation of the audiogenic seizure network by noradrenergic and glutamatergic
      receptors of the deep layers of superior colliculus.
AB  - Recent studies suggest that the deep layers of superior colliculus (DLSC) play a
      role in the network for audiogenic seizures (AGS) in genetically epilepsy-prone
      rats (GEPR-9s). The present study examined the role of glutamatergic and
      noradrenergic receptors in DLSC in modulation of AGS susceptibility. The study
      examined effects of a competitive NMDA receptor antagonist [dl-2-amino-7
      phosphonoheptanoic acid (AP7)] or an alpha1 noradrenergic agonist (phenylephrine)
      focally microinjected into DLSC as compared to effects in the inferior colliculus
      (IC) and pontine reticular formation (PRF), which are major established
      components of the AGS network. The results demonstrated that blockade of NMDA
      receptors in DLSC suppressed AGS susceptibility. AP7 microinjection was effective
      at relatively low doses in IC, but required higher doses in DLSC and PRF. The
      DLSC was relatively more sensitive to seizure reduction by the alpha1
      noradrenergic agonist as compared to the IC and PRF. The anticonvulsant effect of
      AP7 was longer-lasting than phenylephrine in the DLSC and IC but not in the PRF.
      These data suggest that neurons in the DLSC are a requisite component for the
      neuronal network for AGS in GEPR-9s and that NMDA and alpha1 adrenoreceptors in
      this site may play important roles in the modulation of AGS propagation. The
      relatively greater sensitivity of DLSC to phenylephrine as compared to IC and PRF
      indicates that norepinephrine may be more important in the modulation of AGS in
      DLSC, which contrasts to the role of glutamate modulation. These data support
      recent neuronal recording data, which indicate that DLSC neurons play a critical
      role in AGS.

PMID- 10064827
TI  - Cerebral blood flow does not mediate the effect of brain temperature on recovery
      of extracellular potassium ion activity after transient focal ischemia in the
      rat.
AB  - Temperature plays an important role in determining outcome following both global
      and focal brain ischemia. After focal ischemia, the degree of infarction
      decreases with mild hypothermia and increases with mild hyperthermia. In this
      study, brain extracellular potassium ion activity and local cerebral blood flow
      were measured in cerebral cortex during 60 min of middle cerebral artery
      occlusion and 60 min of re-perfusion. Brain temperature was maintained at 32-34
      degrees C (mild hypothermia), 35.5-36.5 degrees C (normothermia), or 37.5-38.5
      degrees C (mild hyperthermia) throughout ischemia and re-perfusion. In
      normothermic animals and to a greater degree in hyperthermic animals,
      extracellular potassium ion activity showed delayed secondary elevation above pre
      ischemia values within 40-60 min after re-perfusion. No secondary elevation of
      extracellular potassium ion activity was observed in hypothermic animals. There
      was no difference in cortical blood flow among groups with varying brain
      temperature, indicating that delayed deterioration of brain potassium ion
      homeostasis was not caused by temperature dependent alteration of cerebral blood
      flow. The data suggest that loss of potassium ion homeostasis during re-perfusion
      after focal cerebral ischemia is caused by cellular rather than vascular
      dysfunction and may reflect secondary inhibition of energy metabolism.

PMID- 10064828
TI  - Differential alteration of phospholipase A2 activities in brain of patients with
      schizophrenia.
AB  - We recently reported that the activity of a calcium-independent subtype of
      phospholipase A2 is increased in blood of patients with schizophrenia. The
      present investigation examined whether similar changes take place in brain of
      patients with this disorder, and for comparison, in patients with bipolar
      disorder. The activity of two classes of PLA2, calcium-stimulated and
      independent, were assayed in autopsied temporal, prefrontal and occipital
      cortices, putamen, hippocampus and thalamus of 10 patients with schizophrenia, 8
      patients with bipolar disorder and 12 matched control subjects. Calcium
      independent PLA2 activity was increased by 45% in the temporal cortex of patients
      with schizophrenia as compared with the controls but was not significantly
      altered in other brain areas. In contrast, calcium-stimulated PLA2 activity was
      decreased by 27-42% in the temporal and prefrontal cortices and putamen, with no
      significant alterations in other brain regions. Brain PLA2 activity was normal in
      patients with bipolar disorder. Calcium-stimulated PLA2 activity was normal in
      cortex, cerebellum and striatum of rats treated acutely or chronically with
      haloperidol, whereas calcium-independent PLA2 activity was decreased in striatum
      of chronically treated animals, indicating that altered PLA2 activity in patients
      with schizophrenia is unlikely to be a direct effect of medication. Studies of
      the cellular role played by PLA2 suggest that decreased calcium-stimulated PLA2
      activity, as also occurs in striatum of chronic human cocaine users, may be due,
      in part, to increased dopaminergic activity in the disorder, whereas increased
      calcium-independent PLA2 activity may be related to abnormal fatty acid
      metabolism and oxidative stress in schizophrenia.

PMID- 10064829
TI  - Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5
      HT1A receptor.
AB  - Modulation of the sexual behavior of male rats by the anxiolytic buspirone (S
      20499) and its analog gepirone were compared to the effects of 8-OH-DPAT (or
      DPAT, a selective 5-HT1A reference agonist), and BMY-7378 (a selective 5-HT1A
      partial agonist). Long-Evans rats were used; modulation of copulatory behavior
      and alteration of penile reflexes were examined. Modulation of copulatory
      behavior was assessed by three indices: frequency and length of intromission, and
      latency of ejaculation. DPAT, at doses of 1-8 mg/kg, reduced these three indices
      in a time dependent manner such that the effects peaked at 45 min and normalized
      at 90 min. The dose-effect relationship (assessed 45 min after DPAT injection) is
      bell-shaped with an ED50 approximately 1 mg/kg on the ascending limb of the
      curve. The effects of buspirone (2 mg/kg) and gepirone (2 mg/kg) on copulatory
      behavior were indistinguishable from control. BMY-7378 alone and in combination
      with these other 5-HT1A agonists reduced copulatory behavior, though not
      statistically significant. Penile reflexes, including number of erections, cups
      and flips, were inhibited by these agents: DPAT>buspirone>gepirone (inactive at 2
      mg/kg). Furthermore, the latency period to erection was at least doubled by DPAT
      (2 mg/kg). Buspirone and gepirone, however, reduced the latency period to
      erection. BMY-7378 inhibited penile reflexes when administered alone and even
      more in combination with DPAT or buspirone. Two butyrophenone analogs, spiperone
      (a 5-HT1A and dopamine D2 antagonist) and haloperidol (a D2 antagonist), were
      also tested for their interaction with DPAT. Both of these drugs (at 0.25 mg/kg,
      60 min after administration) reduced all indices of penile reflexes and
      copulation. Furthermore, in combination with DPAT (2 mg/kg, 45 min), the effects
      were synergistic such that sexual activity came nearly to a standstill. These
      opposing effects on putatively brain originated copulatory behavior and spinal
      mediated penile reflexes indicate that the effects of buspirone and DPAT on
      sexual behavior in the male rat may be possible at different parts of the central
      nervous system. If a tentative shared target site by DPAT and buspirone is the 5
      HT1A receptor, than the same 5-HT receptor sub-type at different locations
      (brain, raphe nuclei, spinal cord and autonomic ganglia) may modulate rat sexual
      behavior in opposing ways.

PMID- 10064830
TI  - Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal
      cord cultures during chemical hypoxia.
AB  - Murine spinal cord primary mixed cultures were treated with the respiratory
      inhibitor, rotenone, to mimic hypoxic conditions. Under these conditions neurons
      rapidly underwent oncosis (necrosis) with a complete loss in viability occurring
      within 260 min; however, astrocytes, which accounted for most of the cell
      population, died more slowly with 50% viability occurring at 565 min. Inosine
      preserved both total cell and neuronal viability in a concentration-dependent
      manner. The time of inosine addition relative to hypoxic insult was critical with
      the most effective protection occurring when inosine was added just prior to or
      within 5 min after insult. Inosine was ineffective when added 30 min after
      hypoxic insult. The effect of guanosine was similar to that of inosine. Treatment
      of cultures with BCX-34, a purine nucleoside phosphorylase inhibitor, prevented
      protection by inosine or guanosine, suggesting involvement of a purine nucleoside
      phosphorylase in the nucleoside protective effect.

PMID- 10064831
TI  - Effect of dopamine denervation and dopamine agonist administration on serine
      phosphorylation of striatal NMDA receptor subunits.
AB  - Sensitization of striatal N-methyl-d-aspartate (NMDA) receptors has been
      implicated in the pathogenesis of the response alterations associated with
      dopaminomimetic treatment of parkinsonian animals and patients. To determine
      whether serine phosphorylation of NMDA receptor subunits by activation of
      Ca2+/calmodulin-dependent protein-kinase II (CaMKII) contributes to this process,
      we examined the effects of unilateral nigrostriatal ablation with 6
      hydroxydopamine and subsequent treatment with levodopa, SKF 38393 (D1-preferring
      dopamine agonist), or quinpirole (D2-preferring agonist) on motor responses and
      phosphorylation states. Three weeks of twice-daily levodopa administration to
      rats shortened the duration of their rotational response to levodopa or SKF 38393
      challenge, but prolonged the duration of quinpirole-induced rotation. At the same
      time, levodopa treatment elevated serine phosphorylation of striatal NR2A
      (p<0.02), but not that of NR2B subunits, without associated changes in subunit
      protein levels. Chronic treatment with SKF 38393 increased NR2A (p<0.0001) but
      decreased NR2B (p<0.004) serine phosphorylation. In contrast, chronic quinpirole
      treatment had no effect on NR2A but increased NR2B phosphorylation (p<0.0001).
      The acute intrastriatal injection of the CaMKII inhibitor KN93 (1.0 micrograms)
      not only normalized the levodopa-induced motor response alterations but also
      attenuated the D1 and D2 receptor-mediated serine phosphorylation of NR2A and
      NR2B subunits, respectively (p<0.02). These results suggest that a CaMKII
      mediated rise in serine phosphorylation of NMDA receptor subunits induced by
      intermittent stimulation of D1 or D2 dopaminergic receptors contributes to the
      apparent enhancement in striatal NMDA receptor sensitivity and thus to the
      dopaminergic response plasticity in levodopa-treated parkinsonian rats.

PMID- 10064832
TI  - Phrenic nerve responses to chemical stimulation of the subregions of ventral
      medullary respiratory neuronal group in the rat.
AB  - Phrenic nerve (PN) responses to unilateral microinjections of L-glutamate (L-Glu,
      5 mM) or N-methyl-D-aspartic acid (NMDA, 1 mM) into different subregions of
      ventral respiratory neuronal group (VRG) were studied in urethane-anesthetized,
      immobilized, and artificially ventilated, adult male Wistar rats. A 50-nl volume
      of microinjection was used in all the subregions of VRG except in Pre-Botzinger
      complex (Pre-BotC) where a 20-nl volume was used. Unilateral microinjections of L
      Glu or NMDA into the Botzinger complex (BotC) and caudal VRG (cVRG), caused a
      transient cessation of phrenic nerve (PN) activity. Expiratory neurons, abundant
      in BotC and cVRG, were excited by stimulation of cardiopulmonary receptors while
      their responses to carotid chemoreceptor stimulation were variable.
      Microinjections of L-Glu or NMDA into the Pre-BotC caused an increase in the PN
      background discharge (this response was unique to Pre-BotC) superimposed on which
      was an increase in the PN burst frequency. Microinjections of L-Glu or NMDA into
      the rostral VRG (rVRG) caused an increase in the frequency and amplitude of PN
      bursts. Inspiratory neurons, abundant in Pre-BotC and rVRG, were excited and
      inhibited by activation of carotid chemoreceptors and cardiopulmonary receptors,
      respectively. The coordinates for the location of different subregions of VRG
      were as follows (reference points are listed in parentheses). BotC: 1.6-2.6 mm
      rostral (calamus scriptorius), 1.7-2.7 mm lateral (midline), and 2.3-2.8 mm deep
      (dorsal surface of medulla); Pre-BotC: 1.4-1.6 mm rostral, 1. 8-2.5 mm lateral,
      and 2.3-2.8 mm deep; rVRG: 0.4-1.4 mm rostral, 1. 6-2.5 mm lateral, and 2.3-2.8
      mm deep; and cVRG: 0.5 mm caudal to 0. 5 mm rostral, 1.0-2.2 mm lateral, and 2.1
      2.6 mm deep. A detailed map of the subregions of VRG, functionally identified by
      L-Glu and NMDA-microinjections, has been presented. These data are likely to
      prove useful in future studies on respiratory reflex mechanisms.

PMID- 10064833
TI  - Neuropeptide Y blocks GABAB-induced phase-shifts of the suprachiasmatic circadian
      clock in vitro.
AB  - The mammalian circadian clock in the suprachiasmatic nucleus (SCN) generates 24-h
      rhythms of neuronal activity in vitro. We have previously shown that the GABAB
      agonist baclofen resets the SCN pacemaker in vitro in a phase-dependent manner:
      advances are induced at zeitgeber time (ZT) 6 and delays are induced at ZT 22. We
      have also previously shown that neuropeptide Y (NPY) phase-shifts the SCN clock
      when applied at ZT 10 but not at other times. Here, we show that NPY blocks the
      baclofen-induced phase-shifts at ZT 6 and ZT 22. The inhibition by NPY appears
      dose-dependent, and a higher concentration of NPY is required for complete
      inhibition of the baclofen-induced phase-advances than the phase-delays.
      Conversely, NPY-induced phase-shifts at ZT 10 are unaffected by co-application of
      baclofen. These results are consistent with previous findings showing that NPY
      blocks in vitro phase-shifts induced by a variety of neuromodulators during both
      the daytime and nighttime.

PMID- 10064834
TI  - Cerebral metabolic profile, selective neuron loss, and survival of acute and
      chronic hyperglycemic rats following cardiac arrest and resuscitation.
AB  - Cortical metabolites and regional cerebral intracellular pH (pHi) were measured
      in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2
      week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest
      and resuscitation. During total ischemia in AH and CH rats (plasma glucose
      approximately 30 mM), cortical ATP, PCr, glucose, and glycogen all fell
      significantly as expected. Lactate levels increased dramatically in association
      with a concomitant intracellular acidosis. Although lactate reached higher
      concentrations in AH and CH than NM, pHi was significantly lower only in the AH
      group. With 5 min of reperfusion, all groups recovered to near baseline in all
      variables, though lactate remained elevated. In a separate aspect of the study,
      animals from each experimental group were allowed to recover for 4 days following
      resuscitation, with outcome being gauged by mortality rate and hippocampal CA1
      neuron counts. NM survival rate was significantly better than AH and CH. In
      particular, no CH rats survived for 4 days despite rapid initial recovery. After
      4 days, the AH group had suffered significantly greater CA1 neuron loss than the
      NM rats. In summary, our research identified differences in intra-ischemic acid
      base status in the two hyperglycemic groups, suggesting that chronic
      hyperglycemia may alter the brain's buffering capacity. These observations may
      account for differences between acutely and chronically hyperglycemic subjects
      regarding outcome, and they suggest that factors other than hydrogen ion
      production during ischemia are responsible for modulating outcome.

PMID- 10064836
TI  - Multiple types of spontaneous excitatory synaptic currents in salamander retinal
      ganglion cells.
AB  - Spontaneous and light-evoked excitatory postsynaptic currents (sEPSCs and
      leEPSCs) in retinal ganglion cells of the larval tiger salamander were recorded
      under voltage clamp conditions from living retinal slices. sEPSCs were isolated
      from the spontaneous inhibitory postsynaptic currents (sIPSCs) by application of
      100 M picrotoxin+1 microM strychnine. In addition to the previously reported
      sEPSCs [K. Matsui, N. Hosoi, M. Tachibana, Excitatory synaptic transmission in
      the inner retina: pair recordings of bipolar cells and neurons of the ganglion
      cell layer, J. Neurosci. 18 (1998) 4500-4510; W.R. Taylor, E. Chen, D.R.
      Copenhagen, Characterization of spontaneous excitatory synaptic currents in
      salamander retinal ganglion cells, J. Physiol. 486 (1995) 207-221] [which are
      equivalent to our fast AMPA receptor-mediated sEPSCs (fAMPAsEPSCs)], we found
      another type of AMPA receptor-mediated sEPSC with slower rise and decay time
      courses and larger peak amplitudes (sAMPAsEPSCs), and the NMDA receptor-mediated
      sEPSCs (NMDAsEPSCs) in ON-OFF ganglion cells. The frequency of all three types of
      sEPSCs is greatly reduced by cobalt (with zero calcium) and increased by
      hyperosmotic solution, suggesting that these events are mediated by calcium
      dependent exocytosis of glutamatergic synaptic vesicles. The amplitude histograms
      of sEPSCs do not show multiple peaks, suggesting that larger events are not
      discrete multiples of elementary events, or quanta, of similar neurotransmitter
      contents, as in the neuromuscular junction [P. Fatt, B. Katz, Spontaneous
      subthreshold activity at motor nerve endings, J. Physiol. 117 (1952) 109-128].
      The average I-V relations of the fAMPAsEPSCs and sAMPAsEPSCs were outward
      rectified with reversal potentials at -12.2 mV and -10.8 mV, and that of the
      NMDAsEPSCs was N-shaped with a reversal potential at -5.8 mV. The average
      conductance increase associated with a single fAMPAsEPSC, a single sAMPAsEPSC,
      and a single NMDAsEPSC were 163. 26+/-51.02 pS, 233.33+/-163.64 pS, and 37.5+/
      50.0 pS at -110 mV; 241.67+/-22.92 pS, 444.90+/-469.94 pS, and 25.93+/-70.37 pS
      at -60 mV; and 440.48+/-183.33 pS, 1,192.68+/-651.22 pS, and 517.71+/-238. 24 pS
      at +30 mV, respectively. The average frequency of the three sEPSCs at +30 mV were
      15 Hz, 3.7 Hz and 3.6 Hz, respectively. The rise time (time to peak) of
      fAMPAsEPSCs was 1.5+/-1.05 ms and the decay time could be fitted with a single
      exponential with an average time constant of 3.4+/-4.1 ms. The rise and decay
      time course of the sAMPAsEPSCs and NMDAsEPSCs were much slower and sawtooth
      shaped, and each 'sawtooth' had time course and amplitude similar to those of
      individual fAMPAsEPSCs. We propose that each fAMPAsEPSC is mediated by single or
      synchronized multiples of glutamatergic synaptic vesicles from bipolar cells, and
      each sAMPAsEPSC or NMDAsEPSC is mediated by larger clusters of synaptic vesicles
      triggered by spontaneous calcium spikes in bipolar cell axon terminals [J.
      Burrone, L. Lagnado, Electrical resonance and calcium influx in the synaptic
      terminal of depolarizing bipolar cells from the goldfish retina, J. Physiol. 505
      (1997) 571-584; D. Zenisek, G. Matthews, Calcium action potentials in retinal
      bipolar neurons, Vis. Neurosci. 15 (1998) 69-75].

PMID- 10064835
TI  - Characterization of mechanical withdrawal responses and effects of mu-, delta-
      and kappa-opioid agonists in normal and mu-opioid receptor knockout mice.
AB  - Clinical and experimental observations suggest that opiates can exert different
      influences on the perception of stimuli from distinct sensory modalities.
      Thermally-induced nociception is classically responsive to opiate agonists. mu
      Opioid receptor-deficient transgenic mice are more sensitive to thermal
      nociceptive stimuli and morphine fails to attenuate the nociceptive responses to
      thermal stimuli in these animals. To enhance our understanding of opiate
      influences on mechanical sensitivity, we have examined withdrawal responses to a
      sequence of ascending forces of mechanical stimuli in mice with normal (wild
      type), half-normal (heterozygous) and absent (homozygous) mu-opioid receptor
      levels. We report data from mice examined without drug pretreatment or following
      pretreatment with morphine, the selective kappa-opioid agonist, U50488H, and the
      selective delta-opioid agonist, DPDPE. Saline-pretreated mice of each genotype
      displayed similar, monotonically increasing frequency of withdrawal responses to
      the graded stimuli. Subcutaneously administered morphine produced a dose
      dependent reduction in withdrawal responses in wild type and heterozygous mice,
      but had no significant effect in homozygous mice. Intraventricular administration
      of DPDPE also reduced the frequency of paw withdrawal (FPW) in wild type mice,
      but not in homozygous mice. In contrast, systemic U50488H produced a dose
      dependent attenuation of paw withdrawal in both wild type and homozygous mice.
      These findings suggest that (1) interactions of endogenous peptides with mu
      opioid receptors may not play a significant role in the response to mechanical
      stimuli in drug-free animals, and (2) deficiency of mu-opioid receptors has no
      functional consequence on the response to the prototypical kappa-opioid receptor
      agonist, but decreases responses to the prototypical mu- and delta-opioid
      receptor agonists.

PMID- 10064837
TI  - Effects of combined medial septal area, fimbria-fornix and entorhinal cortex
      tetrodotoxin inactivations on passive avoidance response consolidation in the
      rat.
AB  - On the basis of previous experimental evidence, it has been concluded that the
      entorhinal cortex (EC), the fimbria-fornix (FF) complex and medial septal area
      (MSA) do not take part in the consolidation phase of passive avoidance response
      (PAR) memorization. On the other hand, a mnemonic role during consolidation of at
      least two of these structures has been argued, based on several considerations.
      In order to ascertain whether the EC and FF are still involved in PAR
      memorization during consolidation, the coupled fully reversible functional
      tetrodotoxin (TTX) inactivation of MSA, FF and EC was performed in rats having
      undergone a PAR training. In Experiment 1 MSA, FF and EC were inactivated pair
      wise (FF and EC always bilaterally). Permanently cannulated animals were injected
      stereotaxically with TTX (5 ng in 0.5 microliter saline) or saline (0.5
      microliter) immediately following PAR acquisition. It was shown that combined FF
      EC inactivation induced PAR retention impairment, whereas FF-MSA and EC-MSA
      inactivation was not followed by amnesic effects. Having obtained a positive
      result, in Experiment 2 the combined FF-EC inactivation was performed at
      different post-acquisition delays (0.25 h, 1.5 h, 6 h), so as to assess the
      duration of their involvement in PAR consolidation. It was shown that only the
      coupled inactivation performed at the shortest post-acquisition delay was
      followed by amnesic effects. Thus EC and FF play a definite role during early
      consolidation. The results are discussed in relation to EC, FF, MSA, and
      hippocampal involvement in PAR memorization, as reported in previous studies, and
      to their connectivity.

PMID- 10064838
TI  - Ferritin, transferrin and iron concentrations in the cerebrospinal fluid of
      multiple sclerosis patients.
AB  - The concentrations of ferritin, transferrin and iron were measured in the
      cerebrospinal fluid (CSF) of multiple sclerosis (MS) and control patients.
      Ferritin levels were significantly elevated in the CSF of chronic progressive
      active MS patients (4.71+/-0.54 ng/ml) compared to levels in normal individuals
      (3.07+/-0.17 ng/ml). MS patients with active or stable relapsing-remitting
      disease had ferritin levels that were comparable to those found in normal
      individuals. There were no significant differences in transferrin or iron levels
      in the CSF between MS and normal individuals. Both ferritin and transferrin
      levels were elevated in patients that had high CSF IgG values but not in patients
      with a high IgG index. Since ferritin binds iron, the increase of CSF ferritin
      levels in chronic progressive MS patients could be a defense mechanism to protect
      against iron induced oxidative injury. Ferritin levels could be a laboratory
      measure that helps to distinguish between chronic progressive and relapsing
      remitting MS.

PMID- 10064839
TI  - Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor
      effects in mice, compared with dextromethorphan and dextrorphan.
AB  - Dextromethorphan ((+)-3-methoxy-N-methylmorphinan, DM) has been shown to have
      both anticonvulsant and neuroprotective effects. The mechanisms of these CNS
      effects of DM have been suggested to be associated with the low-affinity,
      noncompetitive, N-methyl-d-aspartate (NMDA) antagonism of DM and/or the high
      affinity DM/sigma receptors. DM is largely O-demethylated into the phencyclidine
      (PCP)-like compound dextrorphan (DR), which may limit its therapeutic use by
      producing PCP-like adverse effects, such as hyperlocomotion. Dimemorfan ((+)-3
      methyl-N-methylmorphinan, DF), an analog of DM, which has been safely used as an
      antitussive for more than 20 years, is also known not to form DR. This study
      therefore characterized the binding of DF to the sigma receptors and NMDA-linked
      PCP sites and examined the anticonvulsant as well as locomotor effects of DF in
      mice in comparison with those of DM and DR. We found that DF, DM, and DR were
      relative high-affinity ligands at sigma-1 receptors (Ki=151, 205, 144 nM,
      respectively) while all of them were with low affinity at sigma-2 receptors (Ki=4
      11 microM). Only DR exhibited moderate affinity for PCP sites (Ki=0.9 microM),
      whereas DF (Ki=17 microM) and DM (Ki=7 microM) were much less active. DF, DM and
      DR produced prominent anticonvulsant effects in mice as measured by the
      supramaximal electroshock test with comparable potency (ED50 approximately 70
      micromol/kg, i.p.). At the tested doses (20-260 micromol/kg, i.p.), DM and DR
      exhibited biphasic effects on the locomotor activity whereas DF produced a
      consistent dose-dependent decrease. These results revealed that, unlike DM and
      DR, DF did not cause a PCP-like hyperlocomotion adverse effect that is parallel
      with the PCP sites binding data. Furthermore, since they have equipotent
      anticonvulsant effects and similar binding affinities to sigma-1 receptors, the
      very low affinity of DF at PCP sites may suggest that acting on the PCP sites may
      not be the requisite for mediating the anticonvulsant activity of these DM
      analogs. With the history of safety and relative less adverse effects, DF appears
      to be worth further studying on its CNS effects other than the antitussive
      effect.

PMID- 10064840
TI  - Withdrawal from butorphanol dependence alters binding of [3H]phorbol dibutyrate
      to protein kinase C, but not of [3H]forskolin to adenylate cyclase.
AB  - The time course of autoradiographic binding of major second messengers in the rat
      brain was studied at 2, 7, and 24 h after withdrawal from butorphanol infusion.
      [3H]Forskolin and [3H]phorbol 12,13-dibutyrate (PDBu) were used to label
      adenylate cyclase and protein kinase C (PKC), respectively. Rats were rendered
      dependent by intracerebroventricular infusion of butorphanol (26 nmol microliter
      1 h-1) via osmotic minipumps for 3 days. Withdrawal was initiated by abrupt
      cessation of the butorphanol infusion. The levels of [3H]forskolin binding were
      not changed at any time or in any brain area, except for an increase following 7
      h of withdrawal in the brainstem only. The levels of [3H]PDBu binding were
      significantly increased (13-47%) in multiple areas of the rat brain following 7 h
      of withdrawal from butorphanol infusion. These findings suggest that the
      phosphoinositide cycle system is more susceptible to alteration during
      butorphanol dependence than is the adenylate cyclase system in the rat brain.

PMID- 10064841
TI  - Effect of lateral cerebroventricular injection of the appetite-stimulating
      neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of
      rats.
AB  - The effect of lateral cerebroventricular injection of the appetite-stimulating
      neuropeptide, orexin and neuropeptide Y (NPY), on the behavior of rats was
      investigated. An immediate increase in face washing activity was observed after
      injection of orexin A or orexin B, but not NPY. Orexin A had a more potent effect
      on face washing behavior than orexin B. Grooming and burrowing activities also
      increased significantly after injection of orexin A, whereas, orexin B
      significantly increased burrowing and searching behavior. Feeding behavior and
      food consumption increased dramatically within 10 min of injection of NPY.
      Although the significant increase in feeding behavior was also observed after
      injection of orexin A, total food intake did not change significantly. These
      results suggest that orexin may be involved in the regulation of several other
      behavioral activities in rats, besides feeding.

PMID- 10064842
TI  - Lithium decreases Cl--ATPase activity and increases intracellular Cl-
      concentration in cultured rat hippocampal neurons.
AB  - Under the conditions of stimulated phosphatidylinositol turnover (0. 1 mM
      carbachol plus 20 mM KCl), LiCl (0.1-10 mM) reduced the activity of Cl--ATPase in
      cultured rat hippocampal neurons without affecting Na+/K+- or anion-insensitive
      Mg2+-ATPase. This inhibition of Cl--ATPase was attenuated by the addition of 0.5
      mM inositol to culture media. The intracellular Cl- concentrations of the LiCl
      treated neurons increased in an inositol-sensitive manner.

PMID- 10064843
TI  - Feeding response to central orexins.
AB  - Orexin A and orexin B were microinjected into the perifornical hypothalamus
      (PFH), lateral hypothalamus (LH), hypothalamic paraventricular nucleus (PVN), and
      ventral tegmental area (VTA) of male Sprague-Dawley rats. Orexin B (15 nmol) was
      also injected into the lateral cerebral ventricle (i.c.v.). Orexin A (>/=500
      pmol) stimulated feeding in the PFH and LH, but not in the VTA or PVN. Orexin B
      stimulated feeding only when injected i.c.v.

PMID- 10064844
TI  - Phosphoinositide hydrolysis in vivo with group I metabotropic glutamate receptor
      agonists.
AB  - The present report describes the effect of mGluR agonists and antagonists
      administration on phospholipase C activation by measuring accumulation of [3H]
      inositol monophosphates (IP) in rats pre-labeled with [3H]myo-inositol (i.c.v. 24
      h pre-treatment). The levels of accumulated [3H]IP were then determined from
      clarified tissue homogenates using ion-exchange chromotography. Following lithium
      chloride treatment (10 mg/kg, s.c.), (R/S)-3, 5-dihydroxyphenylglycine (DHPG), a
      selective group I mGluR agonist was found to dose-dependently cause a maximal
      increase in the levels of [3H]IP at 0.3 to 3 micromol/8 microliter i.c.v. with
      lower doses resulting in less efficacious or no responses. This effect was
      temporal-dependent reaching a plateau at 2 h. The DHPG-induced increases in
      [3H]IP were most pronounced in the hippocampus where a 3- to 5-fold increase
      above vehicle was consistently found, but significant approximately 2-fold
      increases were also seen in the cerebellum, striatum and frontal cortex. The
      mixed group I and II agonist, (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic
      acid (1S, 3R-t-ACPD), similarly resulted in dose-dependent increases in [3H]IP
      levels with doses of 1 to 3 micromol i.c.v. Furthermore, this effect was
      enantiomer specific since the less active 1R,3S-t-ACPD failed to alter
      phosphoinositol hydrolysis. Administration of the selective mGluR5 agonist (R/S)
      2-chloro-5-hydroxyphenyl-glycine (CHPG) resulted in a dose-dependent increase in
      hippocampal but not cerebellar levels of [3H]IP, consistent with the receptor
      distribution of the two group I mGluRs. The Group II agonist LY354740
      (1S,2S,5R,6S-2-aminobicycl[3.1.0]hexane-2,6-dicarboxylate monohydrate) and the
      group III agonist L-AP4 (L-(+)-2-amino-4-phosphonobutyric acid) failed to alter
      the levels of [3H]IP. LY341495 (2S-2-amino-2-(1S, 2S-2-carboxycycloprop-1-yl)-3
      (xanth-9-yl)propanoic acid) is a nM potent Group II antagonist. However, LY341495
      has also been found to have microM potency in inhibiting mGluR1 and 5. The
      stimulation of [3H]PI hydrolysis by 1 micromol DHPG was dose-dependently blocked
      by co-administration of the mGluR antagonists, LY341495 at doses that are
      constant with an interaction at Group I mGluR's. Taken together these results
      suggest that stimulation of group I mGluRs results in measurable increases in PI
      hydrolysis in vivo. This method could be quite useful in determining the doses
      and routes of administration of agonists and antagonists that are required to
      interact with group I mGluRs.

PMID- 10064845
TI  - Effects of anaesthetics and lazaroid U-83836E on survival of transplanted rat
      dopaminergic neurones.
AB  - We investigated whether different methods of anaesthesia, used on the pregnant
      rat when collecting embryonic donor tissue, and a lipid peroxidation inhibitor
      (lazaroid U-83836E) affect the survival of grafted embryonic dopaminergic
      neurones in hemiparkinsonian rats. There was no difference in either functional
      recovery or survival of dopaminergic neurones between the different euthanasia
      groups: (a) isoflurane sedation followed by cervical dislocation, (b) equithesin-
      or (c) euthatal-anaesthesia. However, lazaroid-treatment enhanced both
      behavioural recovery and transplant survival.

PMID- 10064846
TI  - Hydroxyl radicals and DNA base damage.
AB  - Modified purine and pyrimidine bases constitute one of the major classes of
      hydroxyl-radical-mediated DNA damage together with oligonucleotide strand breaks,
      DNA-protein cross-links and abasic sites. A comprehensive survey of the main
      available data on both structural and mechanistic aspects of.OH-induced
      decomposition pathways of both purine and pyrimidine bases of isolated DNA and
      model compounds is presented. In this respect, detailed information is provided
      on both thymine and guanine whereas data are not as complete for adenine and
      cytosine. The second part of the overview is dedicated to the formation of.OH
      induced base lesions within cellular DNA and in vivo situations. Before
      addressing this major point, the main available methods aimed at singling out.OH
      mediated base modifications are critically reviewed. Unfortunately, it is clear
      that the bulk of the chemical and biochemical assays with the exception of the
      high performance liquid chromatographic-electrochemical detection (HPLC/ECD)
      method have suffered from major drawbacks. This explains why there are only a few
      available accurate data concerning both the qualitative and quantitative aspects
      of the.OH-induced formation of base damage within cellular DNA. Therefore, major
      efforts should be devoted to the reassessment of the level of oxidative base
      damage in cellular DNA using appropriate assays including suitable conditions of
      DNA extraction.

PMID- 10064847
TI  - Oxidative DNA damage mediated by copper(II), iron(II) and nickel(II) fenton
      reactions: evidence for site-specific mechanisms in the formation of double
      strand breaks, 8-hydroxydeoxyguanosine and putative intrastrand cross-links.
AB  - The role of metal ion-DNA interactions in the Fenton reaction-mediated formation
      of putative intrastrand cross-links, 8-hydroxydeoxyguanosine (8-OHdG) and single-
      and double-strand breaks was investigated. Salmon sperm DNA and pBluescript K+
      plasmid were incubated with hydrogen peroxide and either copper(II), iron(II), or
      nickel(II), which differ in both their affinity for DNA and in the spectrum of
      oxidative DNA damage they induce in Fenton reactions. EDTA was included in these
      incubations according to two different strategies; the first (strategy 1) in
      which DNA and metal ions were mixed prior to the addition of EDTA, the second
      (strategy 2) in which EDTA and metal ions were mixed prior to the addition of
      DNA. The formation of the putative intrastrand cross-links, monitored by 32P
      postlabelling, was not affected by the addition of between 10 microM and 5 mM
      EDTA to the copper(II) Fenton reaction according to strategy 1. In contrast, the
      level of cross-links declined significantly upon inclusion of 20 microM EDTA and
      above when added according to strategy 2. Similarly, formation of these lesions
      declined in the iron(II) Fenton reaction more dramatically upon addition of 5 mM
      EDTA when added according to strategy 2 compared to strategy 1, while the yield
      of cross-links formed in the nickel(II) Fenton reaction declined equally with
      both strategies with up to 25 mM EDTA. The formation of single- and double-strand
      breaks was investigated in plasmid DNA by agarose gel electrophoresis and
      subsequent densitometry. The formation of linear DNA in the iron(II) Fenton
      reaction decreased dramatically upon inclusion of EDTA according to strategy 2,
      while no such decline was observed using strategy 1. In contrast, the formation
      of linear DNA in the copper(II) Fenton reaction decreased upon inclusion of EDTA
      according to both strategies. A decrease in the formation of open-circular DNA
      was also observed upon inclusion of EDTA according to both strategies; however
      this decrease occurred at a lower EDTA concentration in strategy 2 (100 microM)
      compared to strategy 1 (200 microM), and the level of open-circular DNA reached a
      lower level (8. 5% compared to 24.2%). The nickel(II) Fenton reaction generated
      only open-circular DNA, and this was completely inhibited upon addition of 25
      microM EDTA according to both strategies. There was less formation of 8-OHdG in
      the copper(II) and iron(II) Fenton reactions when EDTA was added according to
      strategy 2 than according to strategy 1. These results suggest that a site
      specific mechanism is involved in the formation of double-strand breaks and, to a
      lesser extent, 8-OHdG and the putative intrastrand cross-links, while the
      formation of single-strand breaks is more likely to involve generation of
      hydroxyl radicals in solution.

PMID- 10064848
TI  - The chemistry of DNA damage from nitric oxide and peroxynitrite.
AB  - Nitric oxide is a key participant in many physiological pathways; however, its
      reactivity gives it the potential to cause considerable damage to cells and
      tissues in its vicinity. Nitric oxide can react with DNA via multiple pathways.
      Once produced, subsequent conversion of nitric oxide to nitrous anhydride and/or
      peroxynitrite can lead to the nitrosative deamination of DNA bases such as
      guanine and cytosine. Complex oxidation chemistry can also occur causing DNA base
      and sugar oxidative modifications. This review describes the different mechanisms
      by which nitric oxide can damage DNA. First, the physiological significance of
      nitric oxide is discussed. Details of nitric oxide and peroxynitrite chemistry
      are then given. The final two sections outline the mechanisms underlying DNA
      damage induced by nitric oxide and peroxynitrite.

PMID- 10064849
TI  - Endogenous oxidative damage of mtDNA.
AB  - Almost a decade ago, based on analytical measurements of the oxidative DNA adduct
      8-oxo-deoxyguanosine (oxo8dG), it was reported that mitochondrial DNA suffers
      greater endogenous oxidative damage than nuclear DNA. The subsequent discovery
      that somatic deletions of mitochondrial DNA occur in humans, and that they do so
      to the greatest extent in metabolically active tissues, strengthened the
      hypothesis that mitochondrial DNA is particularly susceptible to endogenous
      oxidative attack. This hypothesis was (and is) appealing for a number of reasons.
      Nevertheless, solid direct support for the hypothesis is lacking. Since the
      initial measurements, attempts to repeat the observation of greater oxidation of
      mitochondrial DNA have resulted in a range of measurements that spans over four
      orders of magnitude. Moreover, this range includes values that are as low as
      published values for nuclear DNA. In the last 2 years or so, it has become
      apparent that the quantification of oxidative DNA adducts is prone to artifactual
      oxidation. We have reported that the analysis of small quantities of DNA may be
      particularly susceptible to such interference. Because yields of mitochondrial
      DNA are generally low, a systematic artifact associated with low quantities of
      DNA may have elevated the apparent level of adduct oxo8dG in mitochondrial DNA
      relative to nuclear DNA in some studies. Whatever the cause for the experimental
      variation, the huge disparity between published measurements of oxidative damage
      makes it impossible to conclude that mitochondrial DNA suffers greater oxidation
      than nuclear DNA. Despite the present confusion, however, there are reasons to
      hypothesize that this is indeed the case. We briefly describe methods being
      developed by a number of workers that are likely to surmount current obstacles
      and allow the hypothesis to be tested definitively.

PMID- 10064850
TI  - Etheno DNA-base adducts from endogenous reactive species.
AB  - Promutagenic etheno (epsilon) adducts in DNA are generated through reactions of
      DNA bases with LPO products derived from endogenous sources or from exposure to
      several xenobiotics. The availability of sensitive methods has made it possible
      to detect three epsilon-adducts in vivo, namely epsilon dA, epsilon dC and N2,3
      epsilon dG. One probable endogenous source for the formation of these adducts
      arises from LPO products such as trans-4-hydroxy-2-nonenal (HNE), resulting in
      highly variable background epsilon-adduct levels in tissues from unexposed humans
      and rodents. The range of background levels of epsilon dAx10-8dA detected inhuman
      tissues was <0.05 to 25 and in rodent tissues 0.02 to 10; the corresponding
      values for epsilon dCx10-8dC were 0.01 to 11 and 0.03 to 24, respectively. Part
      of this variability may be associated with different dietary intake of
      antioxidants and/or omega-6 PUFAs which oxidize readily to form 4
      hydroxyalkenals, as epsilon dA and epsilon dC levels in WBC-DNA of female
      volunteers on a high omega-6 PUFA diet were drastically elevated. Increased
      levels of etheno adducts were also found in the liver of cancer-prone patients
      suffering from hereditary metal storage diseases, i.e., Wilson's disease (WD) and
      primary hemochromatosis (PH) as well as in Long-Evans Cinnamon rats, an animal
      model for WD. Increased metal-induced oxidative stress and LPO-derive epsilon
      adducts, along with other oxidative damage, may trigger this hereditary liver
      cancer. Epsilon-Adducts could hence be explored as biomarkers (i) to ascertain
      the role of LPO mediated DNA damage in human cancers associated with oxidative
      stress imposed by certain lifestyle patterns, chronic infections and
      inflammations, and (ii) to verify the reduction of these epsilon-adducts by
      cancer chemopreventive agents. This article summarizes recent results on the
      formation, occurrence and possible role of epsilon-DNA adducts in carcinogenesis
      and mutagenesis.

PMID- 10064851
TI  - Endogenous formation and significance of 1,N2-propanodeoxyguanosine adducts.
AB  - The detection of 1,N2-propanodeoxyguanosine adducts in the DNA of rodent and
      human tissues as endogenous lesions has raised important questions regarding the
      source of their formation and their roles in carcinogenesis. Both in vitro and in
      vivo studies have generated substantial evidence which supports the involvement
      of short- and long-chain enals derived from oxidized polyunsaturated fatty acids
      (PUFAs) in their formation. These studies show that: (1) the cyclic propano
      adducts are common products from reactions of enals with DNA bases; (2) they are
      formed specifically from linoleic acid (LA; omega-6) and docosahexaenoic acid
      (omega-3) under in vitro stimulated lipid peroxidation conditions; (3) the levels
      of propano adducts are dramatically increased in rat liver DNA upon depletion of
      glutathione; (4) the adduct levels are increased in the liver DNA of the CCl4
      treated rats and the mutant strain of Long Evans rats which are genetically
      predisposed to increased lipid peroxidation; and (5) adduct levels are
      significantly higher in older rats than in newborn rats. These studies
      collectively demonstrate that tissue lipid peroxidation is a main endogenous
      pathway leading to propano adduction in DNA. The possible contribution from
      environmental sources, however, cannot be completely excluded. The mutagenicity
      of enals and the mutations observed in site-specific mutagenesis studies using a
      model 1,N2-propanodeoxyguanosine adduct suggest that these adducts are potential
      promutagenic lesions. The increased levels of the propano adducts in the tissue
      of carcinogen-treated animals also provide suggestive evidence for their roles in
      carcinogenesis. The involvement of these adducts in tumor promotion is speculated
      on the basis that oxidative condition in tissues is believed to be associated
      with this process.

PMID- 10064852
TI  - Lipid peroxidation-DNA damage by malondialdehyde.
AB  - Malondialdehyde is a naturally occurring product of lipid peroxidation and
      prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts with DNA
      to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is
      a pyrimidopurinone called M1G. Site-specific mutagenesis experiments indicate
      that M1G is mutagenic in bacteria and is repaired by the nucleotide excision
      repair pathway. M1G has been detected in liver, white blood cells, pancreas, and
      breast from healthy human beings at levels ranging from 1-120 per 108
      nucleotides. Several different assays for M1G have been described that are based
      on mass spectrometry, 32P-postlabeling, or immunochemical techniques. Each
      technique offers advantages and disadvantages based on a combination of
      sensitivity and specificity. Application of each of these techniques to the
      analysis of M1G is reviewed and future needs for improvements are identified. M1G
      appears to be a major endogenous DNA adduct in human beings that may contribute
      significantly to cancer linked to lifestyle and dietary factors. High throughput
      methods for its detection and quantitation will be extremely useful for screening
      large populations.

PMID- 10064853
TI  - Analysis of DNA-protein crosslinking activity of malondialdehyde in vitro.
AB  - In an attempt to identify endogenous chemicals producing DNA-protein crosslinks,
      we have studied in vitro crosslinking potential of malondialdehyde, a
      bifunctional chemical that is ubiquitously formed as a product of lipid
      peroxidation of polyunsaturated fatty acids. We have found that malondialdehyde
      readily forms crosslinks between DNA and histones under physiological ionic and
      pH conditions. Formation of DNA-protein crosslinks was limited to proteins that
      were able to bind to DNA. Malondialdehyde failed to form DNA-protein crosslinks
      when histone binding to DNA was prevented by elevated ionic strength or when
      bovine serum albumin was used in the reaction mixture. Malondialdehyde-produced
      DNA-histone crosslinks were relatively stable at 37 degrees C with t1/2=13.4
      days. Crosslinking of histones to DNA proceeds through the initial formation of
      protein adduct followed by reaction with DNA. Modification of DNA by
      malondialdehyde does not lead to a subsequent crosslinking of proteins.
      Significant formation of DNA-protein crosslinks was also registered in isolated
      kidney and liver nuclei treated with malondialdehyde. Based on its reactivity and
      stability of the resulting crosslinks, it is suggested that malondialdehyde could
      be one of the significant sources of endogenous DNA-protein crosslinks.

PMID- 10064854
TI  - Estrogen, DNA damage and mutations.
AB  - Estrogen administration to rodents results in various types of DNA damage and
      ultimately leads to tumors in estrogen-responsive tissues. Yet these hormones
      have been classified as nonmutagenic, because they did not induce mutations in
      classical bacterial and mammalian mutation assays. In this review, we have
      discussed the induction by estrogens of DNA and chromosomal damage and of gene
      mutations, because the classical assays were designed to uncover mutations only
      at one specific locus and could not have detected other types of mutations or
      changes in other genes. Various types of estrogen-induced DNA damage include: (a)
      direct covalent binding of estrogen quinone metabolites to DNA; (b) enhancement
      of endogenous DNA adducts by chronic estrogen exposure of rodents; (c) free
      radical generation by metabolic redox cycling between quinone and hydroquinone
      forms of estrogens and free radical damage to DNA such as strand breakage, 8
      hydroxylation of purine bases of DNA and lipid hydroperoxide-mediated DNA
      modification. Two different types of chromosomal damage have also been induced by
      estrogen in vivo and in cells in culture such as numerical chromosomal changes
      and also structural chromosomal aberrations. Gene mutations have been induced in
      several cell types in culture either by the parent estrogen or by reactive
      estrogen quinone metabolites. Furthermore, in estrogen-induced kidney tumors in
      hamsters, several mutations have been observed in the DNA polymerase beta gene
      mRNA. Estradiol also induces microsatellite instability in these kidney tumors
      and in premalignant kidney exposed to estradiol. Although this work is still
      ongoing, it can be concluded that estrogens are complete carcinogens capable of
      tumor initiation by mutation potentially in critical genes. The hormonal effects
      of estrogens may complete the development of tumors.

PMID- 10064855
TI  - Endogenous and background DNA adducts by methylating and 2-hydroxyethylating
      agents.
AB  - Detection of 7-alkylguanine DNA adducts is useful to assess human exposure to and
      the resulting DNA damage caused by simple alkylating agents. The background 7
      methylguanine (7-MG) and 7-hydroxyethylguanine (7-HEG) adduct levels were
      determined in human and rat tissues, using thin-layer chromatography (TLC)
      combined with high pressure liquid chromatography (HPLC). In addition, these two
      adduct levels were also compared in various tissues between smokers and non
      smokers. The results demonstrated that the background level of 7-alkylguanine
      adducts in WBC and lung tissues of non-smokers was 2.9 and 4.0 adducts/107
      nucleotides, respectively. In smokers with lung cancers 7-MG adduct level in lung
      samples (6.3+/-1.9 adducts/107 nucleotides) and in bronchus samples (6.1+/-1.5
      adducts/107 nucleotides) was significantly higher than that in WBC samples (3.3+/
      0.9 adducts/107 nucleotides). 7-HEG adduct levels obtained from the same
      individuals were 0.8+/-0.3 in lung, 1.0+/-0.8 in bronchus and 0.6+/-0.2
      adducts/107 nucleotides in WBC, respectively. Animal studies showed that
      background levels of 7-MG (2.1-2.5 adducts/107 nucleotides) in control rats were
      approximately 2-4-fold higher than 7-HEG levels (0.6-0.9 adducts/107
      nucleotides). After a 3-day exposure to 300 ppm ethene, 7-HEG adducts accumulated
      to a similar extent in different tissues of rats, with the mean adduct level of
      5.6-7.0 in liver, 7.4 in lymphocytes and 5.5 adducts/107 nucleotides in kidney.

PMID- 10064856
TI  - DNA adduct formation from tobacco-specific N-nitrosamines.
AB  - Tobacco-specific N-nitrosamines are a group of carcinogens derived from the
      tobacco alkaloids. They are likely causative factors for cancers of the lung,
      esophagus, pancreas, and oral cavity in people who use tobacco products. The most
      carcinogenic tobacco-specific nitrosamines in laboratory animals are 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL), and N'-nitrosonornicotine (NNN). DNA adduct formation
      from NNK and NNN has been studied extensively and is reviewed here. NNK is
      metabolically activated by cytochromes P450 to intermediates which methylate and
      pyridyloxobutylate DNA. The resulting adducts have been detected in cells and
      tissues susceptible to NNK carcinogenesis in rodents. The methylation and
      pyridyloxobutylation pathways are both important in carcinogenesis by NNK. NNK
      also induces single strand breaks and increases levels of 8-oxodeoxyguanosine in
      DNA of treated animals. NNAL, which like NNK is a potent pulmonary carcinogen, is
      also metabolically activated to methylating and pyridyloxobutylating
      intermediates. NNN pyridyloxobutylates DNA in its rat target tissues, esophagus
      and nasal mucosa. Methyl and pyridyloxobutyl DNA adducts are detected in human
      tissues. The methyl adducts most likely result in part from exposure of smokers
      to NNK, but these adducts are also detected in non-smokers. Some of the methyl
      adducts detected in non-smokers may be due to environmental tobacco smoke
      exposure. There are also potential dietary and endogenous sources of these
      adducts. Pyridyloxobutyl DNA adducts in human tissues result mainly from exposure
      to tobacco-specific N-nitrosamines. In laboratory animals, DNA adduct formation
      and carcinogenicity of tobacco-specific N-nitrosamines are closely correlated in
      many instances, and it is likely that similar relationships will hold in humans.

PMID- 10064857
TI  - DNA damage in humans exposed to environmental and dietary polycyclic aromatic
      hydrocarbons.
AB  - The paper describes recent research on human DNA damage related to environmental
      and dietary polycyclic aromatic hydrocarbon (PAH) exposures. The study
      populations either represent general populations of large geographical regions,
      or their exposure situation may have relevance to the general population. In
      Silesia, Poland, and Northern Bohemia, Czech Republic, where coal-based industry
      and domestic heating are the major sources of PAHs, significant differences have
      been observed in white blood cell DNA adducts and cytogenetic biomarkers between
      environmentally exposed and rural control populations, and significant seasonal
      variations of DNA damage have been detected. Bus drivers, traffic policemen and
      local residents have been involved in biomarker studies in Copenhagen, Athens,
      Genoa and Cairo, and differences have been measured in the level of DNA damage of
      urban and rural populations. Burning of smoky coal in unvented homes in Xuan Wei
      region, China, causes high PAH exposure of residents, which has been reflected in
      DNA adduct levels in different tissues. Indoor wood burning in open fireplaces
      did not increase human DNA adduct levels. Oil-well fires left burning in Kuwait
      after the Persian Gulf war created an unprecedented environmental pollution.
      However, insignificant environmental PAH levels were measured several miles from
      these fires. Aromatic and PAH-DNA adduct levels in white blood cells of US Army
      soldiers were lower during their deployment in Kuwait, than in Fulda, Germany,
      where they were stationed before and after serving in Kuwait. The contribution of
      dietary PAH exposure to blood cell DNA adduct levels had been demonstrated in
      studies in which volunteers consumed heavily charbroiled beef. Environmental
      tobacco smoke did not cause detectable changes, as measured by 32P-postlabelling,
      in DNA adduct levels in non-smokers. In the reviewed studies, observed DNA adduct
      levels were generally in the range of 1 to 10 adducts, and not higher than 40
      adducts in 108 nucleotides. Typically, 1.5 to 3-fold differences have been
      detected in DNA adduct levels between the exposed and control groups.

PMID- 10064858
TI  - Polycyclic aromatic hydrocarbons: correlations between DNA adducts and ras
      oncogene mutations.
AB  - This review describes a series of studies on the tumorigenic activities of
      polycyclic aromatic hydrocarbons (PAHs) in various experimental animal model
      systems, their abilities to form PAH-DNA adducts in target tissues, and their
      abilities to mutate ras oncogenes in PAH-induced tumors. The review is limited to
      those PAHs that do not contain nitrogen, for which ras mutations have been
      detected in induced tumors, and for which some information is available about the
      structures of the DNA adducts induced in the target tissue. In general, PAHs that
      form DNA adducts at deoxyadenosine induce mutations at codon 61, whereas those
      PAHs that form DNA adducts at deoxyguanosine primarily induce mutations at codons
      12 or 13. Those PAHs that induce adducts at both bases induce both types of
      mutations. These correlations provide evidence for the involvement of adduct
      directed mutations in ras in the etiology of these tumors. The induced mutation
      spectra in ras may in fact point back to the identity of the type of adduct
      formed.

PMID- 10064859
TI  - DNA damage by mycotoxins.
AB  - Mycotoxins are toxic fungal metabolites which are structurally diverse, common
      contaminants of the ingredients of animal feed and human food. To date,
      mycotoxins with carcinogenic potency in experimental animal models include
      aflatoxins, sterigmatocystin, ochratoxin, fumonisins, zearalenone, and some
      Penicillium toxins. Most of these carcinogenic mycotoxins are genotoxic agents
      with the exception of fumonisins, which is currently believed to act by
      disrupting the signal transduction pathways of the target cells. Aflatoxin B1
      (AFB1), a category I known human carcinogen and the most potent genotoxic agent,
      is mutagenic in many model systems and produces chromosomal aberrations,
      micronuclei, sister chromatid exchange, unscheduled DNA synthesis, and
      chromosomal strand breaks, as well as forms adducts in rodent and human cells.
      The predominant AFB1-DNA adduct was identified as 8, 9-dihydro-8-(N7-guanyl)-9
      hydroxy-AFB1 (AFB1-N7-Gua), which derives from covalent bond formation between C8
      of AFB1-8,9-epoxides and N7 of guanine bases in DNA. Initial AFB1-N7-guanine
      adduct can convert to a ring-opened formamidopyrimidine derivative, AFB1-FAPY.
      The formation of AFB1-N7-guanine adduct was linear over the low-dose range in all
      species examined, and liver, the primary target organ, had the highest level of
      the adduct. Formation of initial AFB1-N7-guanine adduct was correlated with the
      incidence of hepatic tumor in trout and rats. The AFB1-N7-guanine adduct was
      removed from DNA rapidly and was excreted exclusively in urine of exposed rats.
      Several human studies have validated the similar correlation between dietary
      exposure to AFB1 and excretion of AFB1-N7-guanine in urine. Replication of DNA
      containing AFB1-N7-guanine adduct-induced G-->T mutations in an experimental
      model. Activation of ras protooncogene has been found in AFB1-induced tumors in
      mouse, rat, and fish. More strikingly, the relationship between aflatoxin
      exposure and development of human hepatocellular carcinoma (HHC) was demonstrated
      by the studies on the p53 tumor suppressor gene. High frequency of p53 mutations
      (G-->T transversion at codon 249) was found to occur in HHC collected from
      populations exposed to high levels of dietary aflatoxin in China and Southern
      Africa. Furthermore, AFB1-induced DNA damage and hepatocarcinogenesis in
      experimental models can be modulated by a variety of factors including nutrients,
      chemopreventive agents, and other factors such as food restriction and viral
      infection, as well as genetic polymorphisms.

PMID- 10064860
TI  - Bulky endogenous DNA modifications (I-compounds) -possible structural origins and
      functional implications.
AB  - I-compounds are bulky covalent DNA modifications which increase with age in
      tissues of unexposed laboratory animals and are derived from endogenous DNA
      reactive intermediates of nutrient and oxygen metabolism. They have been
      classified into 2 major groups, i.e., type I and type II. Profiles and levels of
      type I I-compounds show considerable variation depending on species, strain,
      tissue, and gender, but are also affected by diet and chemical and hormonal
      exposures, indicating their formation to be determined by genetic and
      environmental factors. For example, sex hormones, dietary oat lipids, and
      isoprenoids affect their profiles and/or levels in tissue DNA. A gradual
      depletion of many type I I-compounds occurs during carcinogenesis, as many
      carcinogens/tumor promoters significantly reduce their levels, and neoplasms
      display very low levels, apparently independent of growth rate, indicating a loss
      of the ability to form these modified nucleotides. Conversely, dietary
      restriction, the most effective method to retard carcinogenesis and aging,
      significantly elevates type I I-compound levels, as compared to age-matched ad
      libitum-fed animals. Levels of many liver and kidney I-compounds exhibit genotype
      and diet-dependent positive linear correlations with median life span. Formation
      of high levels of oat-related type I I-compounds has been associated with reduced
      formation of carcinogen-induced preneoplastic hepatic foci. These results suggest
      that such DNA modifications may not represent DNA lesions but may rather be
      functionally important. This view is supported by circadian rhythms displayed by
      some I-compounds. Thus, certain type I I-compounds may play a protective role
      against carcinogenesis and age-associated degenerative processes. Type II I
      compounds, on the other hand, represent DNA damage and include several bulky
      lesions, which are enhanced by pro-oxidant carcinogens such as ferric nitrilotri-
      acetate (Fe-NTA) in target organ (kidney) DNA of rodents and are identical to
      products generated by oxidizing DNA or oligonucleotides under Fenton reaction
      conditions in vitro. Some of these products appear to be base-base or base-sugar
      intrastrand crosslinks. Notably, Fe-NTA reduces the levels of type I I-compounds
      in renal DNA. Type II I-compound levels are increased in tissue DNA of normal
      newborn rats. The formation of oxidative DNA lesions in neonates is most likely
      caused by oxidative stress associated with the sudden increase of partial oxygen
      pressure in arterial blood and tissues at birth. In view of the rapid cell
      replication at this developmental stage, endogenous oxidative DNA lesions
      sustained early in life may contribute to the development of cancer and
      degenerative diseases later in life.

PMID- 10064861
TI  - Enhancement of pre-existing DNA adducts in rodents exposed to cigarette smoke.
AB  - Exposure to tobacco smoke has been implicated in the increased incidence of
      cancer and cardiovascular diseases. This report describes various experimental
      studies in animals that were carried out to determine the ability of cigarette
      smoke to form DNA adducts and to define chromatographic nature of the major
      adducts. Tissues from rodents exposed to mainstream or sidestream cigarette smoke
      in nose-only and whole-body exposure systems, respectively, for different
      durations were analyzed for DNA adducts by 32P-postlabeling assay. The results
      showed essentially similar qualitative patterns in various respiratory (lung,
      trachea, larynx) and non-respiratory (heart, bladder) tissues of smoke-exposed
      rats. However, adduct pattern in the nasal mucosa was different. The mean total
      DNA adducts in various tissues expressed as per 1010 nucleotides exhibited the
      following order: heart (700)>lung (420)>trachea (170)>larynx (150)>bladder (50).
      Some qualitatively identical adducts were routinely detected in tissues from sham
      treated rats but at greatly reduced levels (5- to 25-fold). The levels of lung
      DNA adducts increased with the duration of exposure up to 23 weeks and returned
      to control levels 19 weeks after the cessation of exposure. Species-related
      differences in adduct magnitude and patterns were observed among rats, mice and
      guinea pigs; mouse being the most sensitive to DNA damage and guinea pig the
      least sensitive. Whole-body exposure of rats to sidestream cigarette smoke also
      enhanced the pre-existing DNA adducts by several fold in different tissues.
      Selective chromatography, and extractability in butanol suggested lipophilic
      nature of smoke-associated DNA adducts, which were, however, recovered
      significantly better in nuclease P1 than butanol enrichment procedure. The major
      smoke-associated adducts were chromatographically different from any of the
      reference adducts of polycyclic aromatic hydrocarbons (PAHs) co-chromatographed
      with the smoke DNA samples. Because PAH-DNA adducts are recovered with equal
      efficiency by the two enrichment procedures, the above observations suggested
      that smoke-associated adducts are not related to typical PAHs, like
      benzo[a]pyrene. It is concluded that cigarette smoke increased the levels of pre
      existing endogenous DNA adducts (the so-called I-compounds) in animal models and
      that these adducts are unrelated to those formed by typical PAHs.

PMID- 10064862
TI  - Repair of DNA lesions: mechanisms and relative repair efficiencies.
AB  - DNA is frequently damaged by endogenous agents inside the cells. Some exogenous
      agents such as polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the
      environment and may thus contribute to the 'background' DNA damage in humans. DNA
      lesions are normally removed by various repair mechanisms. The major repair
      mechanisms for various DNA lesions are summarized. In contrast to the extensively
      studied repair mechanisms, much less is known about the relative repair
      efficiencies of various DNA lesions. Since DNA repair is a crucial defense
      against carcinogenesis, it may constitute an important factor affecting the
      carcinogenicity of DNA damaging agents. We have adopted a human cell-free system
      for measuring relative DNA repair efficiencies based on the concept of repair
      competition between acetylaminofluorene adducts and other DNA lesions of
      interest. Using this in vitro system, we determined the relative repair
      efficiencies of PAH adducts induced by: anti-(+/-)-benzo[a]pyrene-trans-7,8
      dihydrodiol-9,10-epoxide (BPDE), anti-(+/-)-benz[a]anthracene-trans-3,4
      dihydrodiol-1,2-epoxide (BADE-I), anti-(+/-)-benz[a]anthracene-trans-8,9
      dihydrodiol-10, 11-epoxide (BADE-II), anti-(+/-)-benzo[b]fluoranthene-trans-9, 10
      dihydrodiol-11,12-epoxide (BFDE), anti-(+/-)-chrysene-trans-1, 2-dihydrodiol-3,4
      epoxide (CDE), and anti-(+/-)-dibenzo[a, l]pyrene-trans-11,12-dihydrodiol-13,14
      epoxide (DBPDE). While damage by BPDE, DBPDE, CDE, and BFDE were repaired by
      nucleotide excision repair as efficiently as AAF adducts, the repair of BADE-I
      and BADE-II adducts were significantly slower in human cell extracts. Damage by
      DBPDE at 3 microM in vitro yielded approximately 5-fold higher DNA adducts than
      BPDE as determined by quantitative PCR. This potent DNA reactivity may account in
      part for the potent carcinogenicity of dibenzo[a,l]pyrene. The correlation of
      these results to the carcinogenic properties of the PAH compounds is discussed.
      Furthermore, we show that NER plays a role in AP site repair in vivo in the
      eukaryotic model organism yeast.

PMID- 10064863
TI  - DNA polymerase mutagenic bypass and proofreading of endogenous DNA lesions.
AB  - DNA polymerases differentiate between correct and incorrect substrates during
      synthesis on undamaged DNA templates through the biochemical steps of base
      incorporation, primer-template extension and proofreading excision. Recent
      research examining DNA polymerase processing of abasic, alkylation and oxidative
      lesions is reviewed in light of these discrimination mechanisms. Inhibition of
      DNA synthesis results from correct polymerase discrimination against utilization
      of geometrically incorrect template bases or 3' terminal basepairs. The
      efficiency of translesion synthesis is thus related to the physical structure of
      the lesion containing DNA. However, variations in enzyme structure and kinetics
      result in translesion synthesis efficiencies that are also dependent upon the DNA
      polymerase. With a low probability, polymerase misinsertion events create a 3'
      lesion terminus which is geometrically favored over the correct lesion basepair,
      resulting in mutagenic translesion synthesis. For example, both polymerase alpha
      and polymerase beta appear to require the formation of a stable 3' primer
      template structure for efficient abasic site translesion synthesis. However, the
      enzymes differ as to the precise molecular make-up of the stable DNA structure,
      resulting in different mutational specificities. Similar mechanisms may be
      applicable to oxidative damage, where mutational specificities dependent upon the
      DNA polymerase also have been observed. In vitro reaction conditions also
      influence DNA polymerase processing of lesions. Using an in vitro herpes simplex
      virus thymidine kinase (HSV-tk) gene forward mutation assay, we demonstrate that
      high dNTP substrate concentrations affect the mutagenic specificity of
      translesion synthesis using alkylated templates. The exonuclease-deficient Klenow
      polymerase error frequency for G-->A transition mutations using templates
      modified by N-ethyl-N-nitrosourea (ENU) was four-fold higher at 1000 microM
      [dNTP], relative to 50 microM [dNTP], consistent with an increased efficiency of
      extension of the etO6G.T mispair. Moreover, the frequency of other ENU-induced
      polymerase errors was suppressed when polymerase reactions contained 50 microM
      dNTP, relative to 1000 microM dNTP. The efficiency of proofreading as a
      polymerase error discrimination mechanism reflects a balance between the
      competing processes of 3'-->5' exonuclease removal of mispairs and polymerization
      of the next correct nucleotide. Polymerases that are devoid of a proofreading
      exonuclease generally display enhanced abasic site translesion synthesis relative
      to proofreading-proficient enzymes. In addition, the proofreading exonucleases of
      Escherichia coli Pol I and T4 DNA polymerases have been found to remove mispairs
      caused by abasic sites and oxidative lesions, respectively, resulting in lowered
      polymerase error rates. However, the magnitude of the exonuclease effect is small
      (less than 10-fold), and highly dependent upon the DNA polymerase-exonuclease. We
      have studied proofreading exonuclease removal of alkylation damage in the HSV-tk
      forward assay. We observed no significant reduction in the magnitude of the
      mutant frequency vs. dose-response curves when N-methyl-N-nitrosourea or ENU
      treated templates were used in exonuclease-proficient Klenow polymerase
      reactions, as compared to the exonuclease-deficient polymerase reactions. Thus,
      available data suggest that proofreading excision of endogenous lesion mispairs
      does occur, but the efficiency is dependent upon the lesion and the DNA
      polymerase-exonuclease studied.

PMID- 10064864
TI  - Correlation of DNA adduct levels with tumor incidence: carcinogenic potency of
      DNA adducts.
AB  - The quantitative relationship between DNA adducts and tumor incidence is
      evaluated in this review. All available data on DNA adduct levels determined
      after repeated administration of a carcinogen to rats or mice have been compiled.
      The list comprised 27 chemicals, of all major structural classes of carcinogens.
      For the correlation with tumor incidence, the DNA adduct levels measured at the
      given dose were normalized to the dose which resulted in a 50% tumor incidence
      under the conditions of a 2-year bioassay (TD50 dose). In rat liver, the
      calculated adduct concentration 'responsible' for a 50% hepatocellular tumor
      incidence spanned from 53 to 2083 adducts per 108 nucleotides, for aflatoxin B1,
      tamoxifen, IQ, MeIQx, 2,4-diaminotoluene, and dimethylnitrosamine (in this
      order). In mouse liver, the respective figures were 812 to 5543 adducts per 108
      nucleotides, for ethylene oxide, dimethylnitrosamine, 4-aminobiphenyl, and 2
      acetylaminofluorene. The observed span (40-fold in rats, 7-fold in mice) reflects
      differences between the various DNA adducts to lead to critical mutations. If
      additional carcinogens fit in with this astonishingly narrow range, the
      measurement of DNA adduct levels in target tissue has the potential to be not
      only an exposure marker but an individual cancer risk marker. For toremifen and
      styrene, low levels of DNA adducts were detected in rat liver at the end of a
      negative long-term bioassay. This shows that the limit of detection of DNA
      adducts can be well below the limit of detection of an increased tumor incidence.
      For a cancer risk assessment at low levels of DNA damage, treatment-related
      adducts must be discussed in relation to the background DNA damage and its inter-
      and intraindividual variability.

PMID- 10064865
TI  - Intraindividual variations of DNA adduct levels in humans.
AB  - Reports on intraindividual changes of DNA adduct levels in humans are rare. Most
      of the data available in the literature are from polycyclic aromatic hydrocarbons
      (PAHs) and are measured in white blood cells with 32P-postlabeling or
      immunochemical assays. Surprisingly, environmental exposure can have a larger
      effect on PAH adduct levels than occupational exposure, food or smoking. Highest
      (13-fold) summer/winter increments, due to indoor heating were observed in
      Gliwice, Poland. Further studies of environmental PAH exposure confirm the
      environmental influence on intraindividual changes in PAHs-DNA adduct levels:
      studies of the Teplice program, (Czech Republic) and studies with US soldiers,
      stationed in Germany who went for a 8-week period of duty to Kuwait. Variations
      in occupational exposure, e.g., changing of anode material in aluminium plants
      (elevation factor 3.94), layoffs, reduced working hours in iron foundries or
      vacation also led to intraindividual changes in PAH adduct levels. Increase in
      PAH adduct levels after consumption of charcoal broiled meat evidently depends on
      individual susceptibility, e.g., polymorphism. In one person a 7.4-fold increment
      was observed. PAH adduct levels were not significantly influenced by smoking
      cessation whereas sister chromatid exchanges significantly decreased. Changes in
      occupational exposure to styrene in lamination plants, e.g., due to vacation, did
      not significantly influence styrene-O6-dG adduct levels in lymphocytes and
      granulocytes as determined by 32P-postlabeling. Increase of N7-methylguanine and
      O6-methylguanine levels were followed in white blood cells during treatment of
      cancer patients with dacarbazine and allowed insights into pharmacokinetic
      properties. According to a rough estimation the high increment in the PAHs-DNA
      adduct level of about 13 observed in Gliwice (see above) would result in a
      tentative increase in cancer risk from about 1 death/107 inhabitants to
      approximately 10 deaths/107 inhabitants which, in general, is considered as
      acceptable.

PMID- 10064866
TI  - Comparison of DNA adduct levels associated with exogenous and endogenous
      exposures in human pancreas in relation to metabolic genotype.
AB  - Recently, we examined normal human pancreas tissue for DNA adducts derived from
      either exogenous chemical exposure and/or endogenous agents. In an effort to
      explain the different types and levels of DNA adducts formed in the context of
      individual susceptibility to cancer, we have focused on gene-environment
      interactions. Here, we report on the levels of hydrophobic aromatic amines (AAs),
      specifically those derived from 4-aminobiphenyl (ABP), and DNA adducts associated
      with oxidative stress in human pancreas. Although these adducts have been
      reported in several human tissues by different laboratories, a comparison of the
      levels of these adducts in the same tissue samples has not been performed. Using
      the same DNA, the genotypes were determined for N-acetyltransferase 1 (NAT1), the
      glutathione S-transferase (GST) M1, GSTP1, GSTT1, and NAD(P)H quinone reductase-1
      (NQO1) as possible modulators of adduct levels because their gene products are
      involved in the detoxification of AAs, lipid peroxidation products and in redox
      cycling. These results indicate that ABP-DNA adducts, malondialdehyde-DNA
      adducts, and 8-oxo-2'-deoxyguanosine (8-oxo-dG) adducts are present at similar
      levels. Of the metabolic genotypes examined, the presence of ABP-DNA adducts was
      strongly associated with the putative slow NAT1*4/*4 genotype, suggesting a role
      for this pathway in ABP detoxification.

PMID- 10064867
TI  - What is the significance of increases in background levels of carcinogen-derived
      protein and DNA adducts? Some considerations for incremental risk assessment.
AB  - Improvements in analytical methodology have led to the detection and
      quantification of 'background' levels of a number of DNA and protein adducts.
      Many of these adducts are derived from 'low molecular weight' reactive species
      which may be generated during normal physiological processes, metabolic pathways
      or inflammatory processes. The adducts have been detected using gas
      chromatography-mass spectrometry, HPLC in combination with various detection
      systems, 32P-postlabelling and immunoassay methods. The reliability and accuracy
      of many widely used methods for adduct measurements are discussed with reference
      to several examples where human data is available, namely 4-aminobiphenyl,
      malondialdehyde, methylating agents, ethylene oxide and hydroxyl radical damage.
      The accurate and specific quantitation of 'background' levels of damage is
      essential if reliable estimates of increases in risk associated with incremental
      increases in exposure to exogenous agents are to be calculated. In experimental
      studies using low dose exposures to carcinogens, such as N-nitrosodimethylamine,
      adduct levels in liver correlate closely with tumour incidence. In all
      likelihood, such relationships need to be established for each exposure and, in
      order to be relevant to human risk assessment, need to take into account factors
      such as DNA repair and mutagenic efficiency. Finally, in order to estimate the
      increase in cancer attributable to a given level of external exposure, it is
      clearly important to establish background levels of corresponding DNA damage so
      that the scale of the incremental increase can be calculated.

PMID- 10064868
TI  - Cholinergic receptors in heart and brainstem of rats exposed to nicotine during
      development: implications for hypoxia tolerance and perinatal mortality.
AB  - Cigarette smoking during pregnancy increases the incidence of perinatal mortality
      and Sudden Infant Death Syndrome (SIDS). We have evaluated prenatal or postnatal
      nicotine exposure in developing rats to examine the potential role of altered
      neurotransmitter receptor expression in these processes. Pregnant rats received
      continuous infusions of nicotine throughout gestation, at doses mimicking the
      plasma levels found in smokers. After birth, cardiac M2-muscarinic cholinergic
      receptors, which are responsible for inhibitory autonomic actions, were enhanced
      in the nicotine group, coincidentally with decreases in stimulatory beta
      adrenergic receptors that have been demonstrated previously. Studies of adenylyl
      cyclase activity confirmed that the changes in receptor binding represented
      functional alterations: the stimulatory response to isoproterenol was obtunded by
      prenatal nicotine exposure, whereas the inhibitory response to carbachol was
      enhanced. Elevations of M2-muscarinic receptor binding were not generalized to
      all tissues, as the same prenatal nicotine treatment elicited a reduction in
      these receptors in the brainstem, an effect that has also been noted in infants
      who died of SIDS; we found no effects of prenatal nicotine on brainstem M1
      receptor binding. Postnatal administration of nicotine produced similar brainstem
      receptor effects when treatment was conducted during the first postnatal week but
      not thereafter; postnatal nicotine treatment did not affect cardiac M2-receptor
      binding. Thus, during a critical developmental period, nicotine exposure produces
      cardiac and brainstem receptor imbalances that favor inhibitory responses,
      effects that can contribute to morbidity and mortality evoked by hypoxic
      episodes, such as those experienced during parturition, sleep apnea or airway
      obstruction.

PMID- 10064869
TI  - Choline availability alters embryonic development of the hippocampus and septum
      in the rat.
AB  - Choline availability in the diet during pregnancy alters fetal brain biochemistry
      with resulting behavioral changes that persist throughout the lifetime of the
      offspring. In the present study, the effects of dietary choline on cell
      proliferation, migration, and apoptosis in neuronal progenitor cells in the
      hippocampus and septum were analyzed in fetal brains at different stages of
      embryonic development. Timed-pregnant rats on day E12 were fed AIN-76 diet with
      varying levels of dietary choline for 6 days, and, on days E18 or E20, fetal
      brain sections were collected. We found that choline deficiency (CD)
      significantly decreased the rate of mitosis in the neuroepithelium adjacent to
      the hippocampus. An increased number of apoptotic cells were found in the region
      of the dentate gyrus of CD hippocampus compared to controls (5.5+/-0.7 vs. 1.9+/
      0.3 apoptotic cells per section; p<0.01). Using a combination of
      bromodeoxyuridine (BrdU) labeling and an unbiased computer-assisted image
      analysis method, we found that modulation of dietary choline availability changed
      the distribution and migration of precursor cells born on E16 in the fimbria,
      primordial dentate gyrus, and Ammon's horn of the fetal hippocampus. CD also
      decreased the migration of newly born cells from the neuroepithelium into the
      lateral septum, thus indicating that the sensitivity of fetal brain to choline
      availability is not restricted to the hippocampus. We found an increase in the
      expression of TOAD-64 protein, an early neuronal differentiation marker, in the
      hippocampus of CD day E18 fetal brains compared to controls. These results show
      that dietary choline availability alters the timing of the genesis, migration,
      and commitment to differentiation of progenitor neuronal-type cells in fetal
      brain hippocampal regions known to be associated with learning and memory
      processes in adult brain.

PMID- 10064870
TI  - Neurosteroid modulation of the GABAA receptor in the developing guinea pig
      cerebral cortex.
AB  - Developmental changes in 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone;
      5alpha-3alpha-P) potentiation of muscimol and benzodiazepine binding to the GABAA
      receptor were studied in the guinea pig cerebral cortex at three prenatal ages
      (gestational day (GD) 40, GD 50, GD 62), and three postnatal ages (postnatal day
      (PD) 11, PD 21, PD 61) (term, about GD 68). The number and affinity of
      [3H]flunitrazepam binding sites, and 5alpha-3alpha-P potentiation of [3H]muscimol
      and [3H]flunitrazepam binding to the GABAA receptor were determined at each age.
      There was no age effect on the affinity (Kd) for [3H]flunitrazepam. However, the
      number (Bmax) of [3H]flunitrazepam binding sites doubled between GD 40 and GD 62,
      and then declined slightly to reach adult levels by PD 11. 5alpha-3alpha-P
      produced a concentration-dependent potentiation of [3H]muscimol and
      [3H]flunitrazepam binding at each developmental age examined. The potency (high
      affinity) for 5alpha-3alpha-P potentiation of both [3H]muscimol and
      [3H]flunitrazepam binding was lowest at GD 40, and increased to adult levels by
      GD 62. In contrast, the efficacy for 5alpha-3alpha-P potentiation of both
      [3H]muscimol and [3H]flunitrazepam binding was greatest at GD 40, and decreased
      to adult levels between GD 50 and GD 62. The percentage of high-affinity zolpidem
      binding sites increased in an age-dependent manner from 34.2+/-2.2% at GD 40, to
      reach adult levels by GD 62 (59. 4+/-2.5%). These data suggest that 5alpha-3alpha
      P can modulate GABAA receptors in the immature cerebral cortex, and that changes
      in 5alpha-3alpha-P action are temporally related to changes in GABAA receptor
      benzodiazepine pharmacology late in gestation in the guinea pig.

PMID- 10064871
TI  - Reorganization of the primary afferent termination in the rat spinal dorsal horn
      during post-natal development.
AB  - To study the reorganization of the primary afferent input in the spinal dorsal
      horn during post-natal development, synaptic responses evoked by large Abeta and
      fine Adelta afferents were recorded from substantia gelatinosa (SG) neurons in
      slices obtained from immature (post-natal days 21-23) and mature rats (post-natal
      days 56-60). Threshold stimulus intensities and conduction velocities (CVs) of
      Abeta and Adelta afferents were determined by intracellular recordings of the
      antidromic action potentials from dorsal root ganglion (DRG) neurons isolated
      from immature and mature rats. In immature rats, excitatory postsynaptic currents
      (EPSCs) were elicited by stimulation sufficient to activate Abeta afferents in
      the majority of SG neurons (64.9%, 24 of 37 neurons), while most EPSCs observed
      in mature rats were elicited by stimulation of Adelta afferents (62.5%, 25 of 40
      neurons). These observations suggest that the primary afferents innervating SG
      neurons were reorganized following maturation; Abeta afferents were the
      predominant inputs to the SG neurons in the immature state, thereafter Adelta
      afferents were substituted for the Abeta afferents to convey sensory information
      to the SG neurons. This relatively slow reorganization of the sensory circuitry
      may correlate with slow maturation of the SG neurons and with a delay in the
      functional connections of C afferents to the SG neurons.

PMID- 10064872
TI  - Maturational changes in cerebral lactate and acid clearance following ischemia
      measured in vivo using magnetic resonance spectroscopy and microdialysis.
AB  - Intraischemic hyperglycemia has different effects on neurologic outcome in mature
      vs. immature brain, and may reflect differences in the extent or duration of
      cerebral lactic acidosis. We examined the hypotheses that post-ischemic lactate
      and acid clearance rates depend on the severity of intraischemic cerebral
      acidosis, and that rates of clearance change as a function of brain maturation.
      In vivo 31P and 1H magnetic resonance spectroscopy (MRS) was used to compare
      intracellular acid and lactate clearance rates in newborn and 1-month old swine
      following a 14-min episode of transient near-complete global ischemia. In the
      same animals, in vivo microdialysis was used to determine if extracellular
      lactate clearance changed as a function of cerebral lactic acidosis or differed
      between age groups following ischemia. Plasma glucose concentration was altered
      in individual animals to study a range of intraischemic cerebral lactic acidosis.
      For both age-groups, maximal brain acidosis and lactosis occurred in the post
      ischemia interval, indicating a delay in the re-establishment of oxidative
      metabolism following ischemia. Clearance half-lives of both cerebral acidosis and
      lactosis increase as a function of increased intraischemic cerebral acidosis. For
      either age group, the clearance half-life for acidosis was faster than the half
      life for lactate. However, the subgroup of 1-month old swine who experienced
      severe cerebral acidosis (i.e., pH<6.1) had a longer cerebral lactate clearance
      half-life as compared to the subgroup of newborn animals with a similar severity
      of acidosis. In both age groups, there were comparable maximal increases in
      extracellular lactate concentrations in the post-ischemic period and similar
      rates of decline from the maximum. These results demonstrate that post-ischemic
      lactate and acid clearance are altered by the extent of intraischemic acidosis,
      and the extent of post-ischemic uncoupling between brain acid and lactate
      clearance increases with advancing age. The transmembrane clearance of lactate
      was not a prominent mechanism that differentiated lactate clearance rates between
      newborn and 1-month old swine.

PMID- 10064873
TI  - Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult
      rats: a quantitative electron microscopic immunogold study.
AB  - Transcellular transport of energy substrates across the vascular endothelial
      cells of the brain is accomplished by integral membrane carrier proteins, such as
      the glucose transporter GLUT1 and the monocarboxylic acid transporter MCT1. The
      abundance of these proteins may vary depending on age and nutritional status. In
      this study we compared the expression of MCT1 in cerebral cortex of suckling and
      adult rats to determine whether the former, which use considerably more
      monocarboxylates such as lactate and ketone bodies as fuel than do older rats,
      correspondingly express more MCT1 than adults. Using electron microscopic
      immunogold methods, we found that 17-day old suckling rat pups had 25 times more
      MCT1 labeling in the membranes of capillary endothelial cells than adults. This
      transporter was nearly equally distributed in luminal and abluminal membranes
      with less than 10% of the immunogold particles in the endothelial cytoplasmic
      compartment. The suckling rats also had 15 times more immunogold particles
      associated with pericyte membranes and 19 times heavier labeling of membranes
      associated with astrocytic end feet adjacent to microvessels. Neuropil and
      choroid plexus were lightly labeled. Some MCT1-positive astrocyte and neuron cell
      bodies were observed, suggesting active synthesis of MCT1 by these cells. The
      potential for regulation of expression of MCTs by dietary or other factors may
      have important consequences for the progression and treatment of cerebrovascular
      disorders and other diseases.

PMID- 10064874
TI  - Ribosomal RNA expression in the developing rat olfactory bulb.
AB  - The rat olfactory bulb undergoes rapid postnatal growth, thus requiring the
      continuous production of new proteins. The present study examined the development
      of ribosomes, a key component in protein synthesis, in the bulb using an antibody
      specific to ribosomal RNA (Y10b). Furthermore, the potential role of afferent
      activity on patterns of Y10b immunoreactivity, as well as total RNA production
      (using incorporation of 3H-uridine) was examined by blocking an external naris on
      postnatal day 1 (P1). In control pups, Y10b was restricted to mitral cells at P2,
      with labeling expanding to include all layers by P10. Considerable increases in
      staining density were observed by P30. Although no differences in Y10b
      immunoreactive patterns were seen in naris-occluded animals 12-48 h after
      occlusion, or on P10 or P20, by P30, an apparent decrease in numbers of labeled
      profiles (presumably tufted cells) in the external plexiform layer was found.
      Furthermore, no changes were seen in levels of 3H-uridine incorporation. Despite
      the apparent insensitivity to naris closure, the results indicate that ribosome
      expression, as measured by Y10b immunoreactivity, undergoes rapid postnatal
      changes that parallel general patterns of growth in the rat olfactory bulb.

PMID- 10064875
TI  - Long term depression is expressed during postnatal development in rat visual
      cortex: a role for visual experience.
AB  - Long term forms of synaptic plasticity and in particular LTD/LTP are both present
      in the mammalian visual cortex. However, while LTP is not inducible in adulthood
      LTD can be elicited in the mature brain, but its developmental pattern is
      unknown. Aim of this work was to investigate whether LTD is expressed during
      postnatal development and if it is modulated by visual experience. To investigate
      these points we have used rat primary visual cortex slices taken at different
      stages of functional maturation process, i.e., postnatal day 17 (P17), P23 and
      P30-35. LTD was assessed by measuring the amplitude of extracellular field
      potentials recorded in cortical layers 2/3 and elicited by low frequency
      stimulation to the white matter. LTD was expressed at all ages investigated
      without significant differences between age groups. These data indicate that LTD
      developmental expression is not temporally related with the period of functional
      maturation of rat visual cortex. Dark rearing from birth to P23 resulted in a
      reduction of LTD amplitude while light deprivation from P17 to P30 did not affect
      LTD expression in comparison to age matched control values. We suggest that light
      imprinting is essential for a normal LTD expression during postnatal development.

PMID- 10064876
TI  - Cation channel control of neurite morphology.
AB  - The development of neuronal polarity and morphology is essential for a
      functioning nervous system. The present study was undertaken to explore whether
      blockade of specific channels alter neuronal morphology. Retinal ganglion cells
      were cultured in the presence of antagonists to NMDA, AMPA/kainate, L-, N-, P-,
      and Q-type voltage-dependent calcium channels (VDCCs). Five parameters were
      measured under these conditions: the number of neurites at the cell body, total
      neurite length, the length of the longest neurite, the number of branch points
      per neurite, and the diameter of the cell soma. Antagonists to NMDA and L-type
      VDCCs reduce the number of neurites at the cell body; antagonists to P- and Q
      type VDCCs increase the number of neurites. Antagonists to the N-type VDCCs
      increase total neurite outgrowth, while antagonists to the NMDA and P-type
      channels reduce total neurite length. Antagonists to the NMDA and L-type channels
      increase the length of a single neurite, while decreasing the number of branch
      points; antagonists to the P- and Q-type VDCCs do essentially the opposite
      increase the number of neurites, while decreasing the length of each. Blockade of
      one or more cation channels in developing retinal ganglion cells significantly
      perturbs neurite morphology. This study may help elucidate part of the role that
      cation channel signaling plays in neuritic development.

PMID- 10064877
TI  - The noradrenergic system influences the fate of Cajal-Retzius cells in the
      developing cerebral cortex.
AB  - Cajal-Retzius cells are neurons prominently located in layer I of the developing
      cerebral cortex. They are the first neurons to be born in the cortex reaching
      maturity long before any other cortical neuronal cell type; later in development
      they degenerate and/or change phenotype. The noradrenergic system, which
      originates in the locus coeruleus in the brain stem, is one of the earliest
      axonal systems to enter the cortex forming contacts with Cajal-Retzius cells in
      layer I. Here we followed the course of development of the Cajal-Retzius cells in
      postnatal life in animals depleted of noradrenaline in the cortex. We found that
      removal of this system after birth resulted in significantly more Cajal-Retzius
      cells during the first 2 weeks of life. This may be due to the observed decline
      in the number of dying cells in layer I of these animals during the same period.
      We speculate that the noradrenergic system regulates the development of Cajal
      Retzius cells which have been implicated in neuronal migration and laminar
      formation in the cerebral cortex.

PMID- 10064878
TI  - Effect of seizures on cerebral hypoxic-ischemic lesions in immature rats.
AB  - The present investigation was designed to study the effect of chemically induced
      seizures on cerebral hypoxic-ischemic (HI) damage in immature animals.
      Accordingly, cerebral HI was produced in 7-day postnatal (p7) rats and p13 rats
      by combined unilateral common carotid artery ligation and hypoxia with 8% oxygen.
      Seizures were induced chemically by the subcutaneous injection of kainic acid
      (KA) or inhalation of flurothyl vapor. Three types of experiments were conducted
      in each age group and for each convulsant. In some animals (group 1), seizures
      were produced at 24 h and again at 6 h prior to HI. In groups 2 and 3, seizures
      were induced 2 h or 24 h post HI, respectively. The results indicate that in
      group 1 animals, the first seizure significantly reduced duration of the second
      seizure challenge 18 h later at both p7 and p13 (p=0.001). Histologic examination
      of brains of animals in group 1 subjected to seizures prior to HI and their HI
      only controls showed that seizures prior to HI conferred protection against
      cerebral damage. This effect was significant for flurothyl seizures in p13 rats
      for all cerebral regions, especially hippocampal CA1 (p=0.0004), and in p7 rats
      for hippocampus (p=0.04) and particularly cerebral cortex (p=0.007). For KA
      seizures, the protective effect was only significant in p13 rats and was limited
      to hippocampal CA regions and subiculum (p=0.0009). Histologic assessment of
      cerebral lesions of p7 and p13 rats in the other two groups showed no significant
      difference between the animals subjected to seizures 2 h or 24 h post HI and
      their HI-only controls (p>0.05). In conclusion, the results of the present study
      provide no evidence that seizures in early postnatal development aggravate pre
      existing cerebral HI damage. They do suggest that seizures prior to HI or prior
      to a second seizure confer tolerance to both conditions.

PMID- 10064879
TI  - Short- and long-periods of neonatal maternal separation differentially affect
      anxiety and feeding in adult rats: gender-dependent effects.
AB  - Environmental manipulations during early development can induce permanent
      alterations in hypothalamic-pituitary-adrenal (HPA) and behavioral responses to
      stressors. However, little is known about the impact of early life experiences on
      appetitive responses. The present investigation assessed the effects of brief
      handling/separation or protracted separation from the dams, on feeding and
      anxiety responses during development. During the first 3 weeks post-partum,
      Sprague-Dawley rat pups were exposed daily to either brief (15 min)
      handling/isolation (H), a more protracted (3 h) period of maternal separation
      (MS), or were not handled (NH). When tested on the elevated plus-maze (at 5-6
      weeks) H groups displayed less anxiety than NH gender-matched controls.
      Surprisingly, so did the MS females. At weaning (Day 22), the MS rats weighed
      significantly less than both the H and NH animals; the difference between the H
      and MS was more robust and persisted throughout the experiment (D 62). The H
      animals of both genders, and the females of the MS group, consumed more of the
      palatable 'snack' than their NH counterparts. The feeding suppressant response to
      the various satiety peptides (bombesin, cholecystokinin, and amylin) was not
      affected by the early life experience, with exception of cholecystokinin (CCK)
      effects, which were more pronounced in H and MS males. These results suggest that
      early life events may contribute to anxiety and/or ingestive disorders such as
      anorexia nervosa, bulimia and obesity.

PMID- 10064880
TI  - MAP5 expression in proliferating neuroblasts.
AB  - MAP5, a microtubule-associated protein present in immature neurons, was found to
      be expressed in the embryonic mouse telencephalic ventricular zone (VZ). Since
      the VZ contains proliferating neuroblasts, the source of most of the neurons of
      the cerebral cortex, this observation raised the possibility that MAP5 is
      expressed by proliferating neuronal progenitors. MAP5-positive mitotic cells were
      observed at the ventricular surface, a finding consistent with progenitors
      expressing MAP5 prior to their last division. This possibility was investigated
      using dissociated, cortical cells in vitro by measuring the expression of MAP5
      and the neuroepithelial marker nestin, together with the incorporation of
      bromodeoxyuridine (BrdU), a thymidine analogue that labels the DNA of
      proliferating cells in the S-phase of the cell cycle. All of the proliferating
      cells expressed nestin. A population of MAP5-positive cells was also found to
      incorporate BrdU; some cells expressed MAP5 within 30 min of BrdU labeling. The
      results suggest that uncommitted neuroblasts express only nestin, with expression
      of MAP5 occurring near the time the cell commits to become a postmitotic neuron
      after the next cell division. Subsequently, cells expressing both MAP5 and nestin
      leave the cell cycle and exit the VZ, lose nestin, and differentiate into
      neurons. Since some cells expressed MAP5 during or shortly after S-phase but
      before mitosis, MAP5 may be the earliest marker to identify neuronal progenitors
      that will become post-mitotic neurons following their next mitosis.

PMID- 10064882
TI  - Expression of brain-2 in the developing olfactory bulb.
AB  - The expression of Brain-2, a POU domain transcription factor, was examined in the
      developing olfactory bulb. Brain-2 was expressed mainly in the output neurons,
      mitral cell and tufted cells in the main olfactory bulb (MOB), and mitral/tufted
      cells (MT cells) in the accessory olfactory bulb (AOB). It was not expressed in
      granular cells in either the MOB or the AOB. Our results suggest that Brain-2 was
      specifically expressed in output neurons but not in interneurons in the
      developing olfactory bulb. Brain-2 may play a role in the development of these
      output neurons.

PMID- 10064881
TI  - Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2
      receptors and of NT1 receptors in the rat brain revealed by in situ
      hybridization.
AB  - The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2)
      mRNA was studied by in situ hybridization in the rat brain and compared with the
      distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was
      absent at birth from all brain structures except the ependymal cell layer lining
      the ventricles. The development of NT2 receptor mRNA followed three ontogenetic
      patterns. The first pattern, involving the majority of the cerebral gray matter,
      was characterized by a continuous increase from postnatal day 5 (P5) to P30. The
      second one, involving regions rich in myelinated fibers such as the corpus
      callosum and lacunosum moleculare layer of the hippocampus, exhibited a
      pronounced increase between P5 and P10, peaked at P15 and was followed by a
      plateau or a slight decrease. The third pattern was observed in the ependymal
      cell layer lining the olfactory and lateral ventricles, where the high labeling
      already present at birth continued to increase during development. These
      different developmental patterns could reflect the variety of cells expressing
      NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter,
      fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In
      contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was
      highly and transiently expressed during the perinatal period in the cerebral
      cortex, hippocampus and striatal neuroepithelium. Other regions, notably the
      ventral tegmental area and substantia nigra compacta, exhibited a gradual
      increase in NT1 receptor signal, reaching adult levels by P21. Both the
      differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs
      suggest different involvement of these two receptors in brain functions and
      development.

PMID- 10064883
TI  - Consequences of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
      blockade during status epilepticus in the developing brain.
AB  - To investigate if AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      receptor activation contributes to acute manifestations and long term
      consequences of status epilepticus (SE), we administered the AMPA receptor
      antagonist NBQX to P35 rats undergoing kainic acid (KA)-induced SE. NBQX (30
      mg/kg/dose) given intraperitoneally (i.p.) at 30, 60 and 90 min after i.p. KA
      injection (12 mg/kg) reduced severity of SE. When tested as adults, rats that had
      received KA and NBQX were similar to controls with no long term impairment in
      visuospatial memory (assessed by the water maze test), or histologic damage in
      the CA1 or CA3 hippocampal subfields. However, both P35 groups, those receiving
      KA alone and those receiving KA and NBQX, had similar rates of spontaneous
      recurrent seizures (SRS). In P15 rats, NBQX resulted in increased acute mortality
      from KA associated SE. These results indicate that the effects of NBQX on KA
      induced SE are age dependent, and that non-NMDA receptor activation contributes
      to the acute manifestations and to the long term sequelae seen after KA-induced
      SE in the prepubescent rat brain.

PMID- 10064884
TI  - Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal
      degeneration and early induction of transcription factor genes in the
      hippocampus.
AB  - To analyze the role of specific genes and proteins in neuronal signaling cascades
      following global cerebral ischemia, it would be useful to have a reproducible
      model of global cerebral ischemia in mice that potentially allows the
      investigation of mice with specific genomic mutations. We first report on the
      development of a model of reversible cardiocirculatory arrest in mice and the
      consequences of such an insult to neuronal degeneration and expression of
      immediate early genes (IEG) in the hippocampus. Cardiocirculatory arrest of 5 min
      duration was induced via ventricular fibrillation in mechanically ventilated NMRI
      mice. After successful cardiopulmonary resuscitation (CPR), animals were allowed
      to reperfuse spontaneously for 3 h (n=7) and 7 days (n=7). TUNEL staining
      revealed a selective degeneration of a subset of neurons in the hippocampal CA1
      sector at 7 days. About 30% of all TUNEL-positive nuclei showed condensed
      chromatin and apoptotic bodies. Immunohistochemical studies of IEG expression
      performed at 3 h exhibited a marked induction of c-Fos, c-Jun, and Krox-24
      protein in all sectors of the hippocampus, peaking in vulnerable CA1 pyramidal
      neurons and in dentate gyrus. In contrast, sham-operated animals (n=3) did not
      reveal neuronal degeneration or increased IEG expression in the hippocampus when
      compared with untreated control animals (n=3). In conclusion, we present a new
      model of global cerebral ischemia and reperfusion in mice with the use of
      complete cardiocirculatory arrest and subsequent CPR. Following 5 min of
      ischemia, a subset of CA1 pyramidal neurons was TUNEL-positive at 7 days. The
      expression of IEG was observed in all sectors of the hippocampus, including
      selectively vulnerable CA1 pyramidal neurons. This appears to be a good model
      which should be useful in evaluating the role of various genes in transgenic and
      knockout mice following global ischemia.

PMID- 10064885
TI  - Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent
      focal cerebral ischemic mouse brain using an adenoviral vector to induce
      overexpression of interleukin-1 receptor antagonist.
AB  - Our previous studies have demonstrated that overexpression of recombinant human
      interleukin-1 receptor antagonist protein (IL-1ra) via gene transfer can reduce
      ischemic brain injury. However, the mechanism of action of IL-1ra in ischemia is
      unclear. Since interleukin-1 can up-regulate intercellular adhesion molecules in
      endothelium, the present study was designed to determine whether overexpression
      of the IL-1ra can reduce the expression of intercellular adhesion molecule-1
      (ICAM-1) after ischemic injury. Normal saline or adenovirus vector (1x109
      particles) encoding the human IL-1ra gene (Ad.RSVIL-1ra) or the Escherichia coli
      LacZ gene (Ad.RSVlacZ) was injected into the right lateral cerebral ventricle of
      adult CD-1 mice. After five days, permanent middle cerebral artery occlusion
      (MCAO) was achieved for 24 h using an intraluminal suture. Cerebral blood flow
      was monitored by transcranial laser Doppler flowmetry to verify the occlusion.
      ICAM-1 protein was quantified using Western blot analysis and localized using
      immunohistochemistry. After MCAO, surface blood flow in the ischemic hemisphere
      was decreased to 9-11% of the baseline. There were fewer ICAM-1 positive vessels
      in the ischemic cortex of the Ad.RSVIL-1ra transfected mice than in the
      Ad.RSVlacZ transfected and saline treated mice (138+/-19 vs. 249+/-25, 284+/-22,
      p<0.05). Western blot analysis shows that ICAM-1 protein decreased 50-60% in the
      Ad. RSVIL-1ra group compared to the other two groups. There were no significant
      differences in the numbers of positive vessels in the ischemic basal ganglia and
      contralateral hemisphere among the three groups. Our studies suggest that IL-1ra
      overexpression can down-regulate the expression of ICAM-1 in the ipsilateral
      cortex in ischemic mice. Interleukin-1 may play an important role in the
      activation of inflammatory reaction during focal cerebral ischemia by promoting
      leukocyte adhesion on the endothelium cells.

PMID- 10064886
TI  - Transport of CSF antibodies to Galpha subunits across neural membranes requires
      binding to the target protein and protein kinase C activity.
AB  - In the light of functional studies, it has been suggested that antibodies
      directed to alpha subunits of G-proteins delivered into cerebrospinal fluid (CSF)
      reached and blocked the function of neural transducer proteins. Current
      understanding indicates that IgGs do not move freely across plasma membranes.
      Therefore, to characterize the uptake of these antibodies by neural cells, anti
      Gi2alpha IgGs were labeled with 125I, fluorescein or with gold particles. The
      expression of Galpha subunits was also reduced by blocking their mRNA with
      antisense oligodeoxynucleotides (ODN). Following intracerebroventricular (icv)
      injection of gold-conjugated anti-Gi2alpha IgGs, electrondense particles entered
      and became distributed in the cytoplasm and plasma membranes of neural cells.
      Scattered particles were also found in dendrites and nuclei. Unlabeled IgGs
      diminished cerebral signals of fluorescein-labeled anti-Galpha IgGs, indicating
      that this uptake can be saturated. Cerebral radiostaining promoted by in vivo
      anti-Gi2alpha 125I-IgGs was almost absent in Gi2alpha knocked-down mice, but not
      after decreasing the quantity of Gzalpha subunits. The immunosignals of CSF anti
      Galpha 125I-IgGs, as well as the impairment of opioid-evoked antinociception,
      were increased by agonist-induced activation of G protein-coupled receptors. The
      impairing effect of the antibodies on opioid-evoked antinociception was prevented
      by agents blocking the cellular uptake of proteins, i.e., cytochalasin B, BSA,
      DMSO, H7, and by down regulation of protein kinase Cbeta1 (PKCbeta1). In mice
      treated with an ODN to PKCbeta1 mRNA, 125I-IgGs to Gi2alpha subunits remained
      bound to periventricular structures and did not spread to deeper areas of the
      CNS. These results indicate that IgGs delivered into the CSF show a saturable
      binding to Galpha subunits that translocate to the external side of the neural
      membrane before being internalized by a PKCbeta1-dependent mechanism.

PMID- 10064887
TI  - Hydrogen peroxide induces nuclear translocation of p53 and apoptosis in cells of
      oligodendroglia origin.
AB  - The observation that apoptosis is an inherent pathway in oligodendrocytes
      development coupled with the notion that wild-type p53 is expressed in these
      cells, prompted us to investigate the interrelationship between the two
      phenomena. Using a permanent oligodendroglia-like cell line (OLN 93), we examined
      the role of p53 protein in apoptosis following a DNA insult induced by a brief
      exposure to H2O2. A marked translocation of p53 from the cytosolic to the nuclear
      compartment was notable by 20 min, following a 5 min treatment with 1 mM H2O2 as
      identified by cell immunostaining. By 48 h following H2O2 addition, nearly 60% of
      the cells exhibited p53 in the nuclei. At this time, a large proportion of the
      cells underwent apoptosis as identified by DAPI nuclear staining. The genotoxic
      induced p53 relocalization appeared to be cell cycle phase specific; thus OLN 93
      cultures enriched for cells in the G0/G1 stage by serum starvation, and abundant
      in nuclear-associated p53, were more susceptible to H2O2-induced apoptosis than
      their untreated counterparts and than double thymidine block, G1/S enriched,
      cultures. Analysis of the expression of p53 downstream genes indicated that p21
      and mdm2 were upregulated following p53 nuclear translocation. From the kinetics
      of protein accumulation, it appears that mdm2 enhancement accelerated the exit of
      p53 from the nucleus to the cytosol. Our results suggest that following stress,
      oligodendroglia-like cells are induced to undergo p53-dependent apoptosis, an
      event that coincides with p53 nuclear translocation and is cell-cycle related.

PMID- 10064888
TI  - Postsynaptic expression of Ca2+-permeable AMPA-type glutamate receptor channels
      by viral-mediated gene transfer.
AB  - The ability to artificially express a particular receptor protein in the
      postsynaptic sites of neurons in the central nervous system (CNS) would be useful
      for the study of synaptic function of cloned receptor genes as well as for gene
      therapy of neurological disorders caused by dysfunction of postsynaptic
      receptors. In this study, we aimed to express the cDNA of unedited GluR2 subunit
      of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type
      glutamate receptor that forms inwardly rectifying and Ca2+-permeable channel in
      CNS neurons by using adenoviral-mediated gene transfer. For this purpose, we have
      constructed a recombinant adenovirus bearing an expression-switching unit, where
      the unedited GluR2 cDNA can be activated by the Cre recombinase-mediated
      excisional deletion of a stuffer DNA interposed between the promotor and the
      coding region. When PC12 cells were infected with this recombinant adenovirus
      together with an adenovirus expressing Cre recombinase, the inwardly rectifying
      and Ca2+-permeable AMPA receptor channels were expressed in nearly 100% of
      infected cells. Two days after co-infection of cultured rat hippocampal neurons
      with these adenoviruses, fast excitatory neurotransmission in the glutamatergic
      synapse was mediated predominantly by the inwardly rectifying and Ca2+-permeable
      AMPA receptor channels. This indicates that the native AMPA receptors in the
      postsynaptic sites of the glutamatergic synapse are replaced rapidly with
      recombinant receptors newly produced by the viral-mediated gene transfer.

PMID- 10064889
TI  - Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat
      brain.
AB  - In non-neuronal tissue, ferritin subunit mRNAs are regulated by post
      transcriptional mechanisms leading to decreased ferritin protein synthesis during
      iron deficiency. Biochemical studies have demonstrated that the cerebral ferritin
      concentration declines during iron deficiency, suggesting that expression of
      ferritin subunit mRNAs in the brain may be regulated by mechanisms similar to
      those of non-neuronal tissue. However, as ferritin expression has been only
      vaguely studied in brain, this hypothesis remains to be tested. We investigated
      the influence of dietary iron deficiency on the cellular distribution of ferritin
      protein using immunohistochemistry and H- and L-ferritin subunit mRNAs by non
      radioactive in situ hybridization. Pregnant rats were subjected to an iron
      depleted diet (6.4 mg/kg) from the day of conception. Litters were kept on the
      same diet until euthanized at the postnatal age of 10 weeks. This treatment
      reduced brain iron levels from approximately 57 to 26 microgram/g. Reducing the
      iron stores reduced histochemical detectable iron and the expression of ferritin
      immunoreactivity in neurons, oligodendrocyte-like and microglia-like cells. In
      normal rats, H- and L-ferritin subunit mRNAs were expressed in virtually all
      neurons and non-neuronal cells. The cerebral expression of the ferritin subunit
      mRNAs was not affected by iron deficiency. The levels of ferritin subunit mRNAs
      in the brain were also unaltered from iron deficiency when examined by Northern
      blotting. In conclusion, brain levels of iron and ferritin protein are highly
      susceptible to dietary iron deficiency, whereas the cerebral expression of H- and
      L-ferritin subunit mRNAs remains unchanged.

PMID- 10064890
TI  - Differential expression of inflammatory mediators in rat microglia cultured from
      different brain regions.
AB  - Microglial cells show a rather uniform distribution of cell numbers throughout
      the brain with only minor prevalences in some brain regions. Their in situ
      morphologies, however, may vary markedly from elongated forms observed in
      apposition with neuronal fibers to spherical cell bodies with sometimes extremely
      elaborated branching. This heterogeneity gave rise to the hypothesis that these
      cells are differentially conditioned by their microenvironment and, therefore,
      also display specific patterns of differential gene expression. In this study,
      microglia were isolated from 2-4 week-old mixed CNS cultures that had been
      prepared from neonatal rat diencephalon, tegmentum, hippocampus, cerebellum and
      cerebral cortex, and were investigated 24 h later. Messenger RNA levels of
      proteins involved in crucial immune functions of this cell type (TNF-alpha, CD4,
      Fcgamma receptor II, and IL-3 receptor beta-subunit) have been determined by semi
      quantitative RT-PCR. The results clearly show, that three of these mRNAs (TNF
      alpha, CD4, Fcgamma receptor II) are differentially expressed in microglia with
      hippocampal microglia displaying the highest levels of these mRNAs. The data
      strongly support the notion that the status of microglial gene expression depends
      on their localization in brain and on specific interactions with other neural
      cell types. Consequently, it is hypothesized that their responsiveness to signals
      arising in injury or disease may vary from one brain region to another.

PMID- 10064891
TI  - Potential involvement of tyrosine kinase pathway in the antagonist induced
      upregulation of the NMDA receptor NR2B subunit in cortical neurons.
AB  - The aim of this study was to study the potential mechanism(s) involved in the
      antagonist induced upregulation of the N-methyl-d-aspartate receptor (NMDA) NR2B
      subunit. The results show that chronic treatment of cortical neurons with
      tyrosine kinase inhibitor (genistein) resulted in downregulation of the NR2B
      subunit polypeptide levels, while daidzein, an inactive analog of genistein, did
      not alter the levels of NR2B subunit, implying that tyrosine kinases may be
      involved in the regulation of the NMDA NR2B subunit content. Chronic treatment of
      cortical neurons with the NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a, d]cycloheptane-5,10-iminemaleate (MK-801) enhanced the membrane
      associated tyrosine kinase activity and upregulated the NR2B receptor subunit.
      These results suggest that MK-801 induced upregulation of NMDA (NR2B) receptor
      subunit might be mediated by tyrosine kinases.

PMID- 10064892
TI  - Diurnal regulation of a DNA binding protein to the period repeat sequence in the
      SCN nuclear extract of rat brain.
AB  - We previously reported the mammalian period repeat mRNA fluctuates during
      circadian time in the rat suprachiasmatic nucleus (SCN) which is considered to be
      a clock pacemaker in mammalian brain. Presently we discovered a period repeat
      sequence (PR) DNA-binding protein in the rat SCN nuclear extract. In the SCN, the
      binding activity of PR DNA-binding protein to (ACAGGC)3 was most highest during
      the late day and most lowest during the late night by electro-mobility shift
      assay (EMSA). In the cortex nuclear extract, the binding of PR DNA-binding
      protein did not show a significant variation during a day. This is the first
      report to show the existence of diurnal regulated PR DNA-binding protein in the
      SCN.

PMID- 10064893
TI  - Expression of the 100-kDa neurotensin receptor sortilin during mouse embryonal
      development.
AB  - Recently, sortilin a non G-protein-coupled receptor has been identified as the
      100-kDa neurotensin receptor. In this paper we describe the expression of its
      gene during mouse embryonal development. We show that the nervous system is the
      main location of sortilin gene expression and that with ongoing development the
      forebrain exhibits the highest accumulation of transcripts.

PMID- 10064894
TI  - Organization of ganglioside synthesis in the Golgi apparatus.

PMID- 10064895
TI  - Identity of heart and liver L-3-hydroxyacyl coenzyme A dehydrogenase.
AB  - Rat heart and liver cDNAs for precursor of L-3-hydroxyacyl-CoA dehydrogenase have
      been cloned and sequenced. The results indicate that these different rat organs
      express identical dehydrogenases. Furthermore, pig heart mRNA for L-3-hydroxyacyl
      CoA dehydrogenase precursor was amplified by reverse transcription-polymerase
      chain reaction, and all the cDNA clones were found to encode a precursor of liver
      L-3-hydroxyacyl-CoA dehydrogenase (X.-Y. He, S.-Y. Yang, Biochim. Biophys. Acta
      1392 (1998) 119-126) but not the well-documented heart form of the dehydrogenase
      (K.G. Bitar et al., FEBS Lett. 116 (1980) 196-198). Sequencing data and other
      evidence establish that the pig, like the rat, has the same dehydrogenase in
      heart and liver. Since the size and structure of pig heart L-3-hydroxyacyl-CoA
      dehydrogenase are identical to the pig liver dehydrogenase, reports that relied
      on the published sequence of the pig heart dehydrogenase need to be re-evaluated.
      For example, the signature pattern of the L-3-hydroxyacyl-CoA dehydrogenase
      family is HXFXPX3MXLXE. Furthermore, the published crystal structure of the pig
      heart dehydrogenase that substantiated each subunit comprising 307 residues with
      a mercury-binding residue at position 204 (J.J. Birktoft et al., Proc. Natl.
      Acad. Sci. U.S.A. 84 (1987) 8262-8266) must be re-examined in accordance with
      this revelation.

PMID- 10064896
TI  - cDNA cloning of 15-lipoxygenase type 2 and 12-lipoxygenases of bovine corneal
      epithelium.
AB  - Bovine corneal epithelium contains arachidonate 12- and 15-lipoxygenase activity,
      while human corneal epithelium contains only 15-lipoxygenase activity. Our
      purpose was to identify the corneal 12- and 15-lipoxygenase isozymes. We used
      cDNA cloning to isolate the amino acid coding nucleotide sequences of two bovine
      lipoxygenases. The translated sequence of one lipoxygenase was 82% identical with
      human 15-lipoxygenase type 2 and 75% identical with mouse 8-lipoxygenase, whereas
      the other translated nucleotide sequence was 87% identical with human 12
      lipoxygenase of the platelet type. Expression of 15-lipoxygenase type 2 and
      platelet type 12-lipoxygenase mRNAs were detected by Northern analysis. In
      addition to these two lipoxygenases, 12-lipoxygenase of leukocyte (tracheal) type
      was detected by polymerase chain reaction (PCR), sequencing, and Northern
      analysis. Finally, PCR and sequencing suggested that human corneal epithelium
      contains 15-lipoxygenase types 1 and 2.

PMID- 10064897
TI  - Comparison of the stability and substrate specificity of purified peroxisomal 3
      oxoacyl-CoA thiolases A and B from rat liver.
AB  - The specific activities and substrate specificities of 3-oxoacyl-CoA thiolase A
      (thiolase A) purified from normal rat liver peroxisomes and 3-oxoacyl-CoA
      thiolase B (thiolase B) isolated from livers of rats treated with the peroxisome
      proliferator clofibrate were virtually identical. The enzymes could be
      distinguished by their N-terminal amino acid sequences, their isoelectric points
      and their stability, the latter being higher for thiolase A. Contrary to thiolase
      B, which showed a marked cold lability in the presence of KCl by dissociating
      into monomers with poor activity, thiolase A retained its full activity and its
      homodimeric structure under these conditions.

PMID- 10064898
TI  - Identification and characterization of alkenyl hydrolase (lysoplasmalogenase) in
      microsomes and identification of a plasmalogen-active phospholipase A2 in cytosol
      of small intestinal epithelium.
AB  - A lysoplasmalogenase (EC 3.3.2.2; EC 3.3.2.5) that liberates free aldehyde from 1
      alk-1'-enyl-sn-glycero-3-phospho-ethanolamine or -choline (lysoplasmalogen) was
      identified and characterized in rat gastrointestinal tract epithelial cells.
      Glycerophosphoethanolamine was produced in the reaction in equimolar amounts with
      the free aldehyde. The microsomal membrane associated enzyme was present
      throughout the length of the small intestines, with the highest activity in the
      jejunum and proximal ileum. The rate of alkenyl ether bond hydrolysis was
      dependent on the concentrations of microsomal protein and substrate, and was
      linear with respect to time. The enzyme hydrolyzed both ethanolamine- and choline
      lysoplasmalogens with similar affinities; the Km values were 40 and 66 microM,
      respectively. The enzyme had no activity with 1-alk-1'-enyl-2-acyl-sn-glycero-3
      phospho-ethanolamine or -choline (intact plasmalogen), thus indicating enzyme
      specificity for a free hydroxyl group at the sn-2 position. The specific
      activities were 70 nmol/min/mg protein and 57 nmol/min/mg protein, respectively,
      for ethanolamine- and choline-lysoplasmalogen. The pH optimum was between 6.8 and
      7.4. The enzyme required no known cofactors and was not affected by low mM levels
      of Ca2+, Mg2+, EDTA, or EGTA. The detergents, Triton X-100, deoxycholate, and
      octyl glucoside inhibited the enzyme. The chemical and physical properties of the
      lysoplasmalogenase were very similar to those of the enzyme in liver and brain
      microsomes. In developmental studies the specific activities of the small
      intestinal and liver enzymes increased markedly, 11.1- and 3.4-fold,
      respectively, in the first approximately 40 days of postnatal life. A plasmalogen
      active phospholipase A2 activity was identified in the cytosol of the small
      intestines (3.3 nmol/min/mg protein) and liver (0.3 nmol/min/mg protein) using a
      novel coupled enzyme assay with microsomal lysoplasmalogenase as the coupling
      enzyme.

PMID- 10064899
TI  - A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic
      characterization.
AB  - Lysophospholipases are critical enzymes that act on biological membranes to
      regulate the multifunctional lysophospholipids; increased levels of
      lysophospholipids are associated with a host of diseases. Herein we report the
      cDNA cloning of a human brain 25 kDa lysophospholipid-specific lysophospholipase
      (hLysoPLA). The enzyme (at both mRNA and protein levels) is widely distributed in
      tissues, but with quite different abundances. The hLysoPLA hydrolyzes
      lysophosphatidylcholine in both monomeric and micellar forms, and exhibits
      apparent cooperativity and surface dilution kinetics, but not interfacial
      activation. Detailed kinetic analysis indicates that the hLysoPLA binds first to
      the micellar surface and then to the substrate presented on the surface. The
      kinetic parameters associated with this surface dilution kinetic model are
      reported, and it is concluded that hLysoPLA has a single substrate binding site
      and a surface recognition site. The apparent cooperativity observed is likely due
      to the change of substrate presentation. In contrast to many non-specific
      lipolytic enzymes that exhibit lysophospholipase activity, hLysoPLA hydrolyzes
      only lysophospholipids and has no other significant enzymatic activity. Of
      special interest, hLysoPLA does not act on plasmenylcholine. Of the several
      inhibitors tested, only methyl arachidonyl fluorophosphonate (MAFP) potently and
      irreversibly inhibits the enzymatic activity. The inhibition by MAFP is
      consistent with the catalytic mechanism proposed for the enzyme - a serine
      hydrolase with a catalytic triad composed of Ser-119, Asp-174 and His-208.

PMID- 10064900
TI  - Low C18 to C20 fatty acid elongase activity and limited conversion of stearidonic
      acid, 18:4(n-3), to eicosapentaenoic acid, 20:5(n-3), in a cell line from the
      turbot, Scophthalmus maximus.
AB  - The TF cell line, derived from a top predatory, carnivorous marine teleost, the
      turbot (Scophthalmus maximus), is known to have a limited conversion of C18 to
      C20 polyunsaturated fatty acids (PUFA). To illuminate the underlying processes,
      we studied the conversions of stearidonic acid, 18:4(n-3), and its elongation
      product, 20:4(n-3), in TF cells and also in a cell line, AS, derived from
      Atlantic salmon (Salmo salar), by adding unlabelled (25 microM), U-14C (1 microM)
      or deuterated (d5; 25 microM) fatty acids. Stearidonic acid, 18:4(n-3), was
      metabolised to 20:5(n-3) in both cells lines, but more so in AS than in TF cells.
      Delta5 desaturation was more active in TF cells than in AS cells, whereas C18 to
      C20 elongation was much reduced in TF as compared to AS cells. Only small amounts
      of docosahexaenoic acid (22:6(n-3)) were produced by both cell lines, although
      there was significant production of 22:5(n-3) in both cultures, especially when
      20:4(n-3) was supplemented. We conclude that limited elongation of C18 to C20
      fatty acids rather than limited fatty acyl Delta5 desaturation accounts for the
      limited rate of conversion of 18:3(n-3) to 20:5(n-3) in the turbot cell line, as
      compared to the Atlantic salmon cell line. The results can account for the known
      differences in conversions of C18 to C20 PUFA by the turbot and the Atlantic
      salmon in vivo.

PMID- 10064901
TI  - Sequence, expression in Escherichia coli, and characterization of
      lysophospholipase II.
AB  - Here we report the sequence, expression in Escherichia coli cells, and
      characterization of a new small-form lysophospholipase named lysophospholipase II
      from mouse embryo. The cDNA clone was found and identified among mouse expressed
      sequence tags in the database search for the homologue of lysophospholipase I
      previously cloned from rat liver (H. Sugimoto et al., J. Biol. Chem. 271 (1996)
      7705-7711). The predicted amino acids sequence contained 231 residues with a
      calculated molecular weight of 24794, and showed 64% identity to that of
      lysophospholipase I with the Gly-X-Ser-X-Gly esterase/lipase consensus. The lacZ
      fusion protein expressed in E. coli cells exhibited lysophospholipase activity
      and reacted with antibody raised against previously purified pig gastric
      lysophospholipase II (H. Sunaga et al., Biochem. J. 308 (1995) 551-557), but not
      with antibody against rat liver lysophospholipase I. The expressed enzyme was
      purified to a specific activity of 0.15 micromol/min per mg by DEAE-Sepharose A
      500 chromatography. The enzyme preferentially utilized zwitterionic
      lysophospholipids in the order of
      lysophosphatidylcholine>lysophosphatidylethanolamine, but poorly acidic
      lysophospholipids, such as lysophosphatidylserine, lysophosphatidylinositol, and
      lysophosphatidic acid. Not only the 1-acyl isomer, but also the 2-acyl isomer
      were deacylated. Northern blot analysis and reverse transcription-polymerase
      chain reaction revealed that lysophospholipase II transcript as well as
      lysophospholipase I transcript was widely distributed in mouse tissues.

PMID- 10064902
TI  - Variation of liver-type fatty acid binding protein content in the human hepatoma
      cell line HepG2 by peroxisome proliferators and antisense RNA affects the rate of
      fatty acid uptake.
AB  - The liver-type fatty acid binding protein (L-FABP), a member of a family of
      mostly cytosolic 14-15 kDa proteins known to bind fatty acids in vitro and in
      vivo, is discussed to play a role in fatty acid uptake. Cells of the hepatoma
      HepG2 cell line endogenously express this protein to approximately 0.2% of
      cytosolic proteins and served as a model to study the effect of L-FABP on fatty
      acid uptake, by manipulating L-FABP expression in two approaches. First, L-FABP
      content was more than doubled upon treating the cells with the potent peroxisome
      proliferators bezafibrate and Wy14,643 and incubation of these cells with [1
      14C]oleic acid led to an increase in fatty acid uptake rate from 0.55 to 0.74 and
      0.98 nmol/min per mg protein, respectively. In the second approach L-FABP
      expression was reduced by stable transfection with antisense L-FABP mRNA yielding
      seven clones with L-FABP contents ranging from 0.03% to 0.14% of cytosolic
      proteins. This reduction to one sixth of normal L-FABP content reduced the rate
      of [1-14C]oleic acid uptake from 0.55 to 0. 19 nmol/min per mg protein, i.e., by
      66%. The analysis of peroxisome proliferator-treated cells and L-FABP mRNA
      antisense clones revealed a direct correlation between L-FABP content and fatty
      acid uptake.

PMID- 10064903
TI  - Caloric restriction leads to regional specialisation of adipocyte function in the
      rat.
AB  - The study analysed the responses of three metabolic parameters in five distinct
      adipose tissue depots to caloric restriction (4 weeks) in the rat. The aims were
      to evaluate whether specific adipose tissue depots were recruited for
      triacylglycerol (TAG) storage and/or mobilisation, and to determine to what
      extent specific adipose tissue depots exhibited preferences for the source of
      fatty acid (FA) for TAG storage. Caloric restriction led to a general enhancement
      of the response of lipoprotein lipase (LPL), FA synthesis and glucose utilisation
      to a meal. Effects were particularly marked in the parametrial, perirenal and
      interscapular depots compared with mesenteric and subcutaneous depots. There was
      no evidence that individual depots selectively expressed a preference for the
      pathways concerned with the generation of FA for storage (the exogenous (LPL) and
      the endogenous (synthesis) pathway). However, the temporal sequence of activation
      of these pathways differed in a manner consistent with a switch from preponderant
      use of FA produced via de novo synthesis during the very early phase of feeding
      towards later use of FA derived from circulating TAG. The overall excursions in
      insulin levels observed in the calorie-restricted rats were comparable to those
      found in free-feeding rats, but the magnitude and the rapidity of the individual
      metabolic responses of the adipocyte were augmented. The data are consistent with
      a general enhancement of insulin sensitivity and responsiveness in adipose tissue
      of calorie-restricted rats, together with adaptive regional specialisation of
      adipocyte function. These adaptations would be predicted to facilitate the
      immediate conservation of dietary nutrients by promoting their storage as the FA
      or glycerol moieties of adipose tissue TAG and thereby to ensure the regulated
      release of FA and glycerol from adipose tissue in accordance with the requirement
      for glucose conservation and/or production.

PMID- 10064904
TI  - Identification of cis-9,10-methylenehexadecanoic acid in submitochondrial
      particles of bovine heart.
AB  - Submitochondrial particles of bovine heart were hydrolyzed by phospholipase A2
      and the products were analyzed by liquid chromatography electrospray ionization
      mass spectrometry. We found a fatty acid with a molecular mass of 268 Da and a
      retention time longer than that of linoleic acid. Next, we synthesized
      organically cis-9,10-methylenehexadecanoic acid, which has a molecular mass
      similar to that of the extracted fatty acid, and characterized its high
      performance liquid chromatography and gas chromatography-mass spectrometry
      profiles. Using these data we were able to identify endogenous cis-9,10
      methylenehexadecanoic acid in rat and human heart and liver tissues that had been
      hydrolyzed by phospholipase A2. This fatty acid was not detected in tissue
      extracts that had not been hydrolyzed by phospholipase A2. Similar amounts of cis
      9, 10-methylenehexadecanoic acid were measured in tissue extracts after total
      hydrolysis. These results suggest that cis-9, 10-methylenehexadecanoic acid is a
      fatty acid component, in the sn-2 position, of phospholipids in some mammalian
      tissue.

PMID- 10064905
TI  - Predominant inhibition of ganodermic acid S on the thromboxane A2-dependent
      pathway in human platelets response to collagen.
AB  - Ganodermic acid S (GAS), a membrane acting agent, exerts multiple effects on
      human platelet function (C.N. Wang et al. (1991) Biochem. J. 277, 189-197). The
      study reported how GAS affected the response of human gel-filtered platelets
      (GFP) to collagen. The agent inhibited cell aggregation by prolonging lag and
      shape change periods and decreasing the initial cell aggregation rate. However,
      the inhibitory efficiency was less than its inhibition on GFP response to U46619,
      a thromboxane (TX) A2 mimetic. In the agent-effect on biochemical events, GAS
      effectively inhibited Ca2+ mobilization, phosphorylation of myosin light chain,
      dense granule secretion and TXB2 generation. The inhibitions might originate from
      blocking Ca2+ mobilization of the TXA2-dependent pathway. GAS partially decreased
      the phosphorylation of most phosphotyrosine proteins from early activation to the
      integrin alphaIIbbeta3-regulated steps. The agent did not affect the
      phosphorylation of three proteins at the steps regulated by integrin
      alphaIIbbeta3. The results suggest that GAS inhibits the collagen response
      predominantly on the TXA2-dependent signaling, and the tyrosine kinase-dependent
      pathway in collagen response plays a major role in aggregation.

PMID- 10064906
TI  - Substrate specificity of lysophospholipase D which produces bioactive
      lysophosphatidic acids in rat plasma.
AB  - Previously we reported that lysophospholipase D in rat plasma hydrolyzes
      endogenous unsaturated lysophosphatidylcholines (LPCs) preferentially to
      saturated LPCs to lysophosphatidic acids with growth factor-like and hormone-like
      activities. In this study, we examined the possibility that association of LPCs
      with different proteins in rat plasma has an effect on the preference of
      lysophospholipase D for unsaturated LPCs. Large portions of various LPCs were
      found to be recovered in the lipoprotein-poor bottom fraction. Furthermore, the
      percentages of LPCs associated with albumin isolated from rat plasma were shown
      not to be consistent with their percentage conversions to lysophosphatidic acids
      by lysophospholipase D on incubation of rat plasma at 37 degrees C. These results
      indicate that distinct distributions of LPCs in the plasma protein fractions are
      not critical factors for the substrate specificity of lysophospholipase D.
      Experiments with Nagase analbuminemic rats suggested that albumin-LPC complexes
      are not necessarily required for the hydrolysis by lysophospholipase D;
      lipoprotein-associate LPCs appeared to be good substrates for the phospholipase.
      We found that both saturated and unsaturated LPCs are present mainly as 1-acyl
      isomers in rat plasma. This result indicates that the preference of
      lysophospholipase D for unsaturated LPCs is not attributable to a difference in
      position of the acyl group attached to the glycerol backbone of LPC. In addition,
      lysophospholipase D was also found to attack choline phospholipids with a long
      chain group and a short chain alkyl group, although their percentage hydrolyses
      were low. Taken altogether, these results suggest that lysophospholipase D shows
      higher affinities for free forms of unsaturated acyl type LPCs equilibrated with
      albumin-bound and lipoprotein-associated forms, than for free forms of saturated
      acyl type LPCs and analogs of platelet-activating factor.

PMID- 10064907
TI  - Signal transduction triggered by lipid A-like molecules in 70Z/3 pre-B lymphocyte
      tumor cells.
AB  - The lipid A (endotoxin) moiety of lipopolysaccharide (LPS) elicits rapid cellular
      responses from many cell types, including macrophages, lymphocytes, and
      monocytes. In CD14 transfected 70Z/3 pre-B lymphocyte tumor cells, these
      responses include activation of the MAP kinase homolog, p38, activation of NF
      kappaB, and transcription of kappa light chains, leading to the assembly of
      surface IgM. In this work, we explored the specificity of the response with
      regard to lipid structure, and the requirement for p38 kinase activity prior to
      NF-kappaB activation in control and CD14 transfected 70Z/3 (CD14-70Z/3) cells. A
      p38-specific inhibitor, SB203580, was used to block p38 kinase activity in cells.
      CD14-70Z/3 cells were incubated with 1-50 microM SB203580, and then stimulated
      with LPS. Nuclear extracts were prepared, and NF-kappaB activation was measured
      using an electrophoretic mobility shift assay. SB203580 did not inhibit LPS
      induced NF-kappaB activation. In addition, LPS failed to activate p38 tyrosine
      phosphorylation in 70Z/3 cells lacking CD14, in spite of rapid NF-kappaB
      activation and robust surface IgM production with appropriate higher doses of
      LPS. LPS stimulation of p38 phosphorylation, NF-kappaB activation, and surface
      IgM expression were all blocked completely by lipid A-like endotoxin antagonists
      whether or not CD14 was present. Acidic glycerophospholipids and ceramides did
      not mimic lipid A-like molecules either as agonists or antagonists in this
      system. Our data support the hypothesis that lipid A-mediated activation of cells
      requires stimulation of a putative lipid A sensor that is downstream of CD14, but
      upstream of p38 and NF-kappaB.

PMID- 10064908
TI  - Short-time effects of neuroactive steroids on rat cortical Ca2+-ATPase activity.
AB  - Recent experimental evidence indicates that some steroid hormones, apart from
      their well-documented genomic actions, could produce non-genomic rapid effects,
      and are potent modulators of the plasma membrane proteins, including voltage- and
      ligand-operated ion channels or G protein-coupled receptors. Neuroactive
      steroids, 17beta-estradiol, testosterone, pregnenolone sulfate and
      dehydroepiandrosterone sulfate, after a short-time incubation directly modulated
      the activity of plasma membrane Ca2+-ATPase purified from synaptosomal membranes
      of rat cortex. The sulfate derivatives of dehydroepiandrosterone and pregnenolone
      applied at concentrations of 10-11-10-6 M, showed an inverted U-shape potency in
      the regulation of Ca2+-ATPase activity. At physiologically relevant
      concentrations (10-8-10-9 M) a maximal enhancement of the basal activity reached
      200%. Testosterone (10-11-10-6 M) and 17beta-estradiol (10-12-10-9 M) caused a
      dose-dependent increase in the hydrolytic ability of Ca2+-ATPase, and the
      activity with the highest concentration of steroids reached 470% and 200%,
      respectively. All examined steroids decreased the stimulatory effect of a
      naturally existing activator of the calcium pump, calmodulin. The present study
      strongly suggests that the plasma membrane calcium pump could be one of the
      possible membrane targets for a non-genomic neuroactive steroid action.

PMID- 10064909
TI  - Evaluation must include vision.

PMID- 10064910
TI  - Rise and fall.

PMID- 10064911
TI  - [Materno-fetal transmission of hepatitis B virus in Ivory Coast. Plea 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- 10064912
TI  - [Family expenses caused by pediatric hospitalization in Niamey (Niger)].
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- 10064913
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- 10064914
TI  - [Space, health and territory in the intertropical zone].

PMID- 10064915
TI  - [Cholera epidemic in Senegal in 1995-1996: an example of geographic approach to
      health].
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- 10064916
TI  - [Geographic determinants of onchocerciasis transmission in a forest-savannah
      transition zone: an example of 2 villages of the Mbam focus (central region,
      Cameroon)].
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 closet 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- 10064917
TI  - [Acquired immunodeficiency syndrome in Brazil and the State of Ceara].
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 moderately 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- 10064918
TI  - [HIV-2 infection in 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- 10064919
TI  - [Geographic approach to urinary schistosomiasis in an average African town, Daloa
      (Ivory Coast)].
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- 10064920
TI  - [Contribution to studies on the modern health care system in the Republic of
      Congo: geographical approach].
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- 10064921
TI  - [Cartography of epidemiologic data. The principal methods of making 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- 10064922
TI  - [Physicians are needed in palliative home care. Quality of home care should be
      equivalent to hospital care].

PMID- 10064923
TI  - [Drugs and environment. Can the industry be a good example?].

PMID- 10064924
TI  - [How Norrkoping took care of the relatives of the Estonia-victims].

PMID- 10064925
TI  - [Cholesterol testing in a department store].

PMID- 10064926
TI  - [Give the relatives time to decide about organ donation].

PMID- 10064927
TI  - [Therapeutic targets in type 2 diabetes: measurement values, end points or
      quality of life...?].

PMID- 10064928
TI  - [Liver transplantation from a living donor is now possible. The first cases in
      Sweden completed with good results].
AB  - Liver transplantation is the sole treatment option for children with chronic
      liver failure, a patient category previously characterised by high mortality due
      to the lack of suitable organs. The introduction of new surgical techniques used
      in 'in situ splitting' of a donor liver, and in living related donor transplants
      has enabled mortality to be reduced. The article consists gives an account of the
      first five procedures where the in situ split technique was used in cadaveric
      livers, and of the first living related liver transplant performed in Sweden. The
      technique will improve the outcome of liver transplantation in children, and
      reduce the risk of death due to long waiting lists.

PMID- 10064929
TI  - [Changed disease panorama of tuberculosis in Vasterbotten. The elderly with
      earlier occurrence of tuberculosis and young immigrants are the greatest risk
      groups].

PMID- 10064930
TI  - [Antibiotic resistance of Helicobacter pylori in Malmo. Therapeutic success in
      spite of antibiotic resistance].
AB  - Triple therapy (omeprazole, clarithromycin and metronidazole) is associated with
      a sensitive Helicobacter pylori (HP) eradication rate of over 90 per cent. As
      treatment failure is mainly due to poor patient compliance, satisfactory patient
      information is vital. Despite the high prevalence (29-40%) of metronidazole
      resistant HP in Malmo, the eradication rate is over 90%. Clarithromycin
      resistance among HP strains has increased in prevalence from 1 to 7% over the
      past four years, and always results in treatment failure. In order to avoid
      unnecessary antibiotic treatment, especially in cases of patients not responding
      to triple therapy, it is important to follow treatment up with, for example, the
      urea breath test.

PMID- 10064931
TI  - [Increased level of TSH can be a sign of adrenal cortex failure. Not necessarily
      thyroid gland disease].

PMID- 10064932
TI  - [Rapid breakthrough for endoscopy in neurosurgery].

PMID- 10064933
TI  - [Critical periods at the intensive care units are documented in diaries].

PMID- 10064934
TI  - [Psychosocial factors are limiting the possibility of dying at home].
AB  - All 151 patients registered at a palliative home care facility in Sollentuna from
      its inception in 1995 to the end of 1997 were studied to identify factors
      contributing to the patients' possibility of dying at home. Of those registered,
      117 had died by the end 1997, 69 at home, 40 at a hospice, seven at emergency
      facilities, and one abroad. Comparison of those who died at a hospice and those
      who died at home showed no significant differences to exist between the two
      subgroups in age, gender, diagnosis, stage of disease, degree of symptom control,
      or treatment given. Psychosocial factors were the most important determinants of
      whether the patients died at home. The availability of psychological support for
      family members, and access to a hospital bed when they needed to relax, were also
      important factors, as were patient and family consent to home care.

PMID- 10064935
TI  - [Pain relief in sports injuries--emergency measures yield good results].
AB  - The reason for an athlete to consult a physician is almost always pain in some
      form. Several non-pharmacological alternative remedies are practised in sports
      medicine, which may be worth knowing about and even of use in other fields of
      medicine. Such practices include compression treatment, body part elevation, and
      cryotherapy, which have precise indications but also important limitations. The
      use of analgesia to mask sports injuries is not only ethically dubious, but also
      difficult practically as it is seldom possible to obtain adequate pain relief
      without significantly impairing performance.

PMID- 10064936
TI  - [A common symptom among athletes and persons who exercise. Correct treatment of
      groin pain requires a meticulous diagnosis].
AB  - Groin pain is common among athletes. In its acute form the pain is usually
      overuse-related and is treated conservatively, whereas in chronic groin pain the
      clinical picture is often more complex. Successful treatment is dependent on
      correct diagnosis, as there are multiple differential diagnosis. Surgery has been
      associated with good results in chronic cases, the most common interventions
      being adductor tenotomy, abdominal wall repair, and neurotomy of the ilioinguinal
      and/or iliohypogastric nerve. Which surgical approach should be adopted is
      dependent on the results of investigation to identify the causative factor.

PMID- 10064937
TI  - ["Tennis elbow" is usually caused by other than tennis. The earlier the treatment
      the better; spontaneous remission occurs often within 8-13 months].
AB  - Although both the incidence and prevalence of tennis elbow (radial
      epicondylalgia) are 1(2 per cent among adults, the disorder is attributable to
      tennis in only about five per cent of cases, even if about 50 per cent of tennis
      players over thirty are affected. The condition often resolves spontaneously in
      8(13 months. The basic diagnostic criteria are tenderness at palpation on the
      radial epicondyle of the humerus, and radial pain on extension of the wrist
      against resistance with the elbow extended. Maudsley's middle finger test, Mill's
      manoeuvre and the chair-lift test will confirm the diagnosis. Treatment outcome
      is best in first-ever cases with a duration of less than three months. In the
      absence of satisfactory documentation, there is no consensus as to which non
      surgical methods are to be preferred. Local cortisone injection provides good
      relief initially, though recurrence within three months is common. Surgery,
      resorted to in cases refractory to other treatment, relatively often yields good
      results, especially if executed earlier than hitherto has been recommended.

PMID- 10064938
TI  - [A computerized system for regional management of incidents is now tested. A
      complement to the Lex Maria system, indicates unobserved risks].

PMID- 10064939
TI  - [Time to change the basis for forming of judgements by the research ethics
      committees? The treatment of persons involved in trials should be scrutinized for
      scientific quality].

PMID- 10064940
TI  - [Quality assurance of the quality work! Poor basic data can totally twist the
      results].

PMID- 10064941
TI  - [Drug information to the patient. The way to tell is more important than what to
      tell].

PMID- 10064942
TI  - [The biological monitoring of occupational exposures to solvents by using their
      urinary concentrations].
AB  - For many years biological monitoring of occupational exposure to solvents is
      achieved via their specific urinary metabolites. In the last 10 years many
      publications have shown that the urinary concentrations of unchanged solvents are
      well correlated with environmental exposure and could therefore be used for
      biological monitoring. For acetone, methanol, methyl ethyl ketone and methyl iso
      butyl ketone, the American Conference of Governmental Industrial Hygienists and
      the Deutsche Forschungsgemeinschaft have proposed urinary concentrations of
      substance itself as biological exposure indices. A critical revision of the
      literature on this matter reveals discrepancies between the results obtained by
      different authors. The correlations between environmental data and respective
      solvents give excellent indices of correlation. However, the differences observed
      when comparing the regression lines obtained from different research groups are
      very wide. For example, for an exposure to toluene corresponding to 50 ppm, some
      authors found urinary concentrations equal to 35 micrograms/l, others found
      urinary concentration higher than 100 micrograms/l. Similarly for benzene,
      styrene and methyl ethyl ketone the differences were also marked. We have not
      identified an explanation for such different results. Biological data variability
      could help to explain part of these disagreements. It should also be remembered
      that for benzene, the analytical methodology performed in different conditions
      can give rise to very different results. The mechanisms of excretion of organic
      solvents in urine are discussed considering biological variability and analytical
      method problems. The current hypotheses do not allow a satisfactory
      interpretation of the literature results. In conclusion further experience is
      needed that will more clearly show which results better express the relationship
      between occupational exposure to organic solvents and their specific urinary
      concentrations.

PMID- 10064943
TI  - [Rhythm and conduction disorders in formulating a judgment of work fitness].
AB  - Assessment of work fitness must take due account of clinical and/or laboratory
      findings, which may at times not be clear, when these are indicative of heart
      "disease". It is, however, necessary to discriminate between invalidating
      conditions which in certain jobs may lead to adverse effects, morphological
      alterations, and/or "benign" rhythm anomalies.

PMID- 10064944
TI  - [An epidemiological study of a group of workers employed in the maintenance of a
      sewer network and of urban waste water treatment plants].
AB  - The paper reports the results of a study on occupational risks of a group of
      sewage workers of the city of Genoa vs. a control group of nonexposed subjects;
      the first group was divided into three subgroups according to the job
      characteristics. After bibliographical research on the topic, a specific
      questionnaire was used to analyse individual symptoms. Clinical examinations,
      blood and respiratory tests were also performed. The statistical analysis was
      performed by evaluating F test for differences between parametric measures and
      the relative risk for non-parametric findings. The relative risk of alterations
      in respiratory function (both instrumental and clinical findings) was increased
      among the water treatment workers. The average platelets count in the exposed
      workers appeared to be significantly reduced compared to non-exposed subjects
      although both were within the normal limits. There was non evidence of an
      increased prevalence of positive A hepatitis markers in the exposed workers.

PMID- 10064945
TI  - [The simultaneous determination of hippuric acid, o-, m-, p-methylhippuric acids,
      mandelic acid and phenylglyoxylic acid in urine by HPLC].
AB  - A high-performance liquid chromatographic method is described for the
      simultaneous determination of six metabolites of aromatic hydrocarbons: hippuric
      acid (HA) from toluene; o-, m-, p-methylhippuric acids (o-, m-, p-MHA) from
      xylene; mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene and
      ethylbenzene. Metabolites were first extracted from urine by solid phase
      extraction with anion exchange resin, then isocratically separated on a C8 column
      with 3 microns particle size, 10 cm length and 3 mm internal diameter. Mobile
      phase was prepared diluting 16 mL of tetrahydrofuran, 14 mL of acetronitrile and
      5 mL of methanol to 500 mL with phosphoric acid/potassium dihydrogen phosphate
      buffer 0.01 M (pH 2.7). The internal standard was 3-hydroxybenzoic acid.
      Chromatographic runs were completed in about 21 min. The accuracy and
      reproducibility obtained make this method useful for the biological monitoring of
      occupational exposure to toluene, xylene, styrene and ethylbenzene.

PMID- 10064946
TI  - [Repetitive movements of the upper extremities: the results of assessing exposure
      to biomechanical overload and of a clinical study in a group of workers employed
      in the production of plywood and veneer panels].
AB  - In a group of 27 female workers employed on the manual "moulding" of plywood
      panels exposure to factors of biomechanical overload for the upper limbs was
      assessed and an anamnestic and clinical examination was made in order to clarify
      the occurrence of a series of WMSDs type diseases and disorders. Data are
      reported on the risk factors, frequency of action (range: right limb-->14.5
      divided by 22.0 actions/min,-->5.5 divided by 11.0 actions/min), use of strength
      (right limb-->Borg 3.7-4.9; left limb-->Borg 3.0-3.8), incongruous postures and
      movements, complementary factors, and on the lack of recovery pauses (4 hours in
      an 8-hour shift). The OCRA indices were: single press: right limb-->146-208; left
      limb-->61-85; multi press: right limb-->4.8-7.1; left limb-->1.1-2.3. The EPM
      method showed that the factors producing greatest overloading were excessive use
      of strength, incongruous postures and movements (specially of wrist, hand and
      elbow) and of complementary factors like constant compression of the palm of the
      right hand, tearing movements and the use of gloves. Clinical examination
      according to EPM showed that tendon disorders (69% of which 34% were carpal
      tunnel syndrome) were the most frequent disorders followed by epicondylosis
      (23%); disorders of the shoulder were less frequent (8%). In view of the clear
      significance of the statistical data of these disorders which were proved to be
      caused by current work organization (Fisher test was highly significant for 65%
      and significant for 75% of the disorders), further diagnostic and therapeutic
      investigations for each single female worker are necessary along with specific
      interventions to improve working conditions. Among the possible prevention
      measures the need is stressed for improvements on tools, on job organization, and
      for an adequate information and training program for all workers.

PMID- 10064947
TI  - [A cohort study of art glass workers in the Empoli area].
AB  - The investigation aimed at studying cause-specific mortality of art glass workers
      employed in 17 industrial facilities in Tuscany, Italy. A cohort of 3390 workers
      employed for at least 1 year was obtained from company payrolls. Follow-up was
      between the year each factory started operations, mostly in the mid-fifties, and
      the end of 1993. The cause specific expected mortality was computed relative to
      Tuscany rates, specified for gender, 5-year age groups and calendar year.
      Separate analyses were carried out for the job titles of makers, batch mixers and
      grinders. For males, 3180 individuals, the observed mortality for cancer causes
      was above the expected for the lung [standardized mortality ratio (SMR) 123, 10
      observed (Obs)], larynx (SMR 166, 10 Obs), stomach (SMR 105, 30 Obs) and brain
      (SMR 150, 7 Obs). For non-cancer causes observed mortality was above expected for
      hypertensive diseases (SMR 178, 10 Obs) and diseases of the genitourinary system
      (SMR 169, 11 Obs). Increases for the above listed causes were shown also among
      makers. Mortality for larynx and lung cancer increased with time since first
      exposure and significantly increased SMRs were observed for 21 or more years
      since first exposure: this pattern was still present with smoking adjustment. The
      results showed consistently increased mortality for lung and larynx cancer in the
      overall cohort and among makers. Stomach cancer, brain cancer, hypertensive
      diseases and diseases of the genitourinary system were also increased in the
      overall cohort and among makers.

PMID- 10064948
TI  - Occupational hepatitis B virus infection in sewage workers.
AB  - In a cross-sectional study the employees of a Sewage Company were tested for
      hepatitis B virus (HBV) markers--HBsAg, anti-HBs, anti-HBc--to determine the
      prevalence of HBV infection and assess the risk of exposed sewage workers
      becoming infected, so as to evaluate the necessity for appropriate vaccination.
      The overall prevalence of HBV markers was 43.9% and 6.6% of the employees were
      HBsAg carriers. In the univariate analysis the prevalence of past and current
      infection was significantly associated with exposure to sewage (p < 0.001), age
      (p < 0.001) and with educational level (p < 0.001). However, the logistic
      regression analysis confirmed that only exposure to sewage was independently
      associated with positivity for HBV infection (p < 0.001). Workers exposed to
      sewage should therefore be considered for vaccination against hepatitis B virus.

PMID- 10064949
TI  - [Is a risk assessment of carcinogenic agents possible?].

PMID- 10064950
TI  - [Risk assessment or a presumption of the same?].

PMID- 10064951
TI  - [Clinical and radiological study of pulmonary actinomycosis].
AB  - We clinically and radiologically examined 8 patients with pulmonary
      actinomycosis. Their clinical features were slowly progressive, and the most
      commonly occurring symptom was hemoptysis. Laboratory findings disclosed elevated
      ESRs, a sign of chronic inflammation. Roentgenographic films showed a higher
      percentage of lesions in the right lung and on the dorsal side. On chest CT
      images, the lesions appeared as nodular or consolidated shadows with atelectasis,
      and spread widely over the parietal pleura in the periphery of the lung fields.
      The margins of the nodules were irregular, and multiple blood vessels were
      involved. The internal density of the nodules contained either a low attenuation
      region or cavity. In relation to the pleural, local pleural thickening adjacent
      to the nodules was identified in all patients, and the thickened areas were thin
      and smooth. Although it was difficult to diagnose by transbronchial lung biopsy
      (TBLB), granulation tissue obtained by TBLB was considered an important finding
      suggestive of pulmonary actinomycosis. As diagnostic procedures, repeated TBLBs
      appear to be effective for lesions extending into the hilar region, and video
      assisted thoracoscopic surgery, for small nodular lesions located in the
      periphery of the lung fields.

PMID- 10064952
TI  - [Estimated numbers of patients with intractable respiratory diseases].
AB  - To estimate the number of patients with intractable respiratory diseases, we
      conducted a two-stage nationwide epidemiological survey in 1997. The first survey
      was performed at randomly sampled hospitals to identify the number of patients
      treated. The second survey sought detailed clinico-epidemiological data on the
      patients reported in the first survey. The response rates were 54% for the first
      survey and 62% for the second. Based on the survey findings, we derived the
      following nationwide estimates: 450 patients (95% confidence interval: 360-530)
      with chronic thromboembolic pulmonary hypertension; 230 (200-260) with primary
      pulmonary hypertension; 180 (150-210) with obesity-associated hypoventilation
      syndrome; 40 (30-50) with primary alveolar hypoventilation syndrome; 160 (140
      180) with histiocytosis X; and 190 (150-230) with juvenile pulmonary emphysema.

PMID- 10064953
TI  - [Long-term effects of nasal continuous positive airway pressure on pulmonary
      function and blood gas data in patients with obstructive sleep apnea syndrome].
AB  - To evaluate the long-term effects of nasal continuous positive airway pressure
      (NCPAP) on pulmonary function and blood gas levels in patients with obstructive
      sleep apnea syndrome (OSAS), we examined the pulmonary functions and blood gases
      in 25 male patients with OSAS before and after NCPAP treatment. After 22 months
      of treatment (titration: 13 cm H2O), no significant changes were observed in the
      patients' spirograms, pulmonary gas volumes, or diffusion capacity. However, PaO2
      levels increased significantly (p < 0.01), from 73.8 mmHg to 79.5 mmHg; PaCO2
      levels decreased significantly (p < 0.05), from 45.6 mmHg to 44.2 mmHg; and A
      aDO2 levels also decreased significantly (p < 0.05), from 18.7 mmHg to 15.0 mmHg.
      The patients were divided into a hypoventilated group (PaCO2 > 45 mmHg; 11 cases)
      and normoventilated group (PaCO2 < or = 45 mmHg; 14 cases). After NCPAP
      treatment, increased PaO2 and decreased PaCO2 levels were observed in the
      hypoventilated group, and increased PaO2 and decreased A-aDO2 levels were
      observed in the normoventilated group. These results suggest that long-term NCPAP
      treatment improves gas exchange in OSAS patients without influencing the results
      of pulmonary function tests.

PMID- 10064954
TI  - [MPO-ANCA related diffuse alveolar hemorrhage].
AB  - The purpose of this study was to elucidate the clinical features characterizing
      patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO
      ANCA) related diffuse alveolar hemorrhage (DAH). Seventeen MPO-ANCA-positive
      patients were evaluated. Nine patients (52.9%) had pulmonary involvement; of
      those, 6 (35.3%) had DAH, and 4 (23.5%) had interstitial pneumonia (1 patient had
      both pulmonary diseases). Three of the patients with DAH demonstrated only mildly
      bloody sputum. All patients with DAH had increased peripheral white blood cell
      counts, high titers of C-reactive protein and MPO-ANCA, and marked microscopic
      hematuria. DAH was diagnosed in all cases by fiberoptic bronchoscopy with
      bronchoalveolar lavage. All patients with DAH were treated with three pulses of
      methylprednisolone, and 5 were treated with cyclophosphamide. Three of the
      patients with DAH required mechanical ventilation for respiratory insufficiency,
      but 2 were relieved of that need by immunosuppressive therapy. In spite of
      intensive care, 1 patient died of respiratory failure and 2 died of complications
      related to therapy. The prognosis for patients with DAH is poor. We emphasize the
      importance of prompt and accurate diagnoses and aggressive care, including
      immunosuppressive therapy, mechanical ventilation, and hemodialysis. In addition,
      extra precautions should be taken against opportunistic infections such as
      Pneumocystis carinii pneumonia.

PMID- 10064955
TI  - [Severe respiratory distress caused by dental foreign object].
AB  - A 77-year-old man hospitalized in a bedridden state for cerebral infarction and
      left hemiparesis experienced the sudden onset of dyspnea and cyanosis. Chest X
      ray films detected a foreign object in the hilum of the left lung. Emergency
      bronchoscopy revealed a dental crown lodged in the second carina. It was not
      possible to remove the crown with bronchoscopy forceps. The patient suffered
      severe respiratory failure the following day. Bronchoscopy again was performed,
      and the foreign object was removed with basket-type forceps. It was the patient's
      first molar, covered with a crown. The patient's respiratory failure was caused
      by atelectasis of the left lower lobe and overinflation, of the right lung, both
      of which resulted from postoperative edema of bronchial mucous membrane. Dental
      foreign objects do not cause pulmonary atelectasis or pneumonia as easily as
      other types of bronchial foreign objects. Therefore, there is usually enough time
      for thorough examination prior to removal procedures. It is important to
      accurately identify the shape of the foreign object, choose appropriate forceps,
      and successfully remove the object in the first operation. Moreover, adequate
      dental treatment of caries and loose teeth is important as a means of preventing
      dental foreign objects, especially in elderly people and bedridden patients.

PMID- 10064956
TI  - [Mediastinal neurilemmoma originating in the right phrenic nerve: a case report].
AB  - We report on a 31-year-old man with a mediastinal neurilemmoma originating in the
      right phrenic nerve. The patient was admitted because of abnormal chest X-ray
      shadows observed during a routine checkup. A preoperative diagnosis of bronchial
      cyst in the mediastinum was made. The tumor was resected by video-assisted
      thoracic surgery. It was 3 x 4 x 3 cm in size, weighted 15 g, and originated in
      the right phrenic nerve. The histopathologic diagnosis was mediastinal
      neurilemmoma. Only 14 cases have been reported in the Japanese literature.

PMID- 10064957
TI  - [Squamous cell lung cancer with minimal-change nephrotic syndrome].
AB  - We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year
      old man was admitted because of proteinuria and microhematuria. A plain chest X
      ray film on admission showed a large mass in the left-lower lung field. The
      patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous
      cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid
      therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced
      the lung cancer, alleviated the proteinuria, and completely resolved the
      nephrotic syndrome. Nephrotic syndrome is generally associated with malignant
      lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial
      neoplasms are less common, but lung cancer is one of the most widely reported.
      Histologically, most cases of cancer-associated nephrotic syndrome exhibit
      membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of
      immunocomplex on glomerular basement membrane are considered to play a pathogenic
      role in membranous nephropathy. However, the pathogenesis of minimal-change
      nephrotic syndrome is different.

PMID- 10064958
TI  - [Pulmonary cryptococcosis exhibiting diffuse multiple nodular shadows].
AB  - We report a case of pulmonary cryptococcosis showing diffuse multiple nodular
      shadows in all lung fields. A 39-year-old woman with no immunological
      abnormalities was admitted with complaints of cough and sputum. She had
      experienced measles 4 weeks prior to admission. Chest x-ray films revealed
      diffuse nodular opacities throughout the lung fields, a finding suggestive of
      metastatic lung cancer. Detailed examinations, including transbronchial lung
      biopsy, were not conclusive. A diagnosis of pulmonary cryptococcosis was made on
      the basis of findings from video-assisted thoracoscopic biopsy. Primary pulmonary
      cryptococcosis usually appears as a solitary nodule or limited infiltration.
      Immunologically compromised hosts commonly demonstrate various abnormal shadows,
      such as the multiple nodular shadows observed in our patient. It has been
      reported that measles infection can cause temporary immune suppression. Secondary
      immunodeficiency resulting from the preceding infection with measles could
      explain the unusual chest x-ray findings in this case.

PMID- 10064959
TI  - [A case of thymic carcinoma producing granulocyte colony-stimulating factor].
AB  - A 73-year-old man was admitted complaining of chest pain and weight loss. A chest
      X-ray film and chest CT scan showed a tumorous mass in the anterior mediastinum
      with moderate pleural effusion. Percutaneous needle biopsy specimens from the
      mass resulted in a diagnosis of poorly differentiated squamous cell carcinoma of
      the thymus. Laboratory findings on admission showed marked leukocytosis with no
      evidence of infection or bone marrow metastasis. The level of serum granulocyte
      colony-stimulating factor (G-CSF) was abnormally high (79.2 pg/ml, normal < 30).
      Carcinoma cells in the specimen showed positive staining with anti G-CSF
      monoclonal antibody, thus indicating that they produced G-CSF. Because multiple
      metastatic lesions on the chest wall and liver were detected, we performed
      combination chemotherapy with cisplatin, vindesine and mitomycin C. After 2
      courses of chemotherapy, a decrease in tumor size was verified by CT scan. As the
      tumor size decreased, the patients white blood cell count and serum G-CSF
      concentration fell to normal levels.

PMID- 10064960
TI  - [Summer-type hypersensitivity pneumonitis with remarkable obstructive impairment
      of pulmonary function].
AB  - A 57-year-old-man was admitted because of persistent cough and progressive
      dyspnea over a period of 2 months. Examination revealed wheezing in both lungs,
      severe hypoxemia, and marked obstructive impairment of pulmonary function. A
      chest CT scan showed diffuse small nodular lesions with patchy air space
      opacifications. The patient was initially given a diagnosis of bronchiolitis of
      unknown cause. He showed marked improvement after treatment with oral
      prednisolone, but developed fever and dyspnea after returning home. This episode
      indicated hypersensitivity pneumonitis, a diagnosis supported by findings of
      increased CD 8 positive T-lymphocytes in bronchoalveolar lavage fluid, and a high
      titer of serum anti-Trichosporon antibody. Lung biopsy samples obtained under
      video-assisted thoracoscopy disclosed noncaseating granulomas in terminal and
      respiratory bronchioles, which resulted in marked narrowing of the lumen. The
      pathologic changes seemed to be consistent with obstructive impairment of
      pulmonary function in this patient.

PMID- 10064961
TI  - [A case of cervical-mediastinal lymph node tuberculosis progressed to pulmonary
      lesion through a bronchial fistula].
AB  - The patient was a 25-year-old man who had been admitted to a local hospital due
      to fever and trachelophyma. Tubercle bacillus was detected in pus culture
      obtained by biopsy of the trachelophyma, but not in sputum culture. Because
      combined therapy with 3 antituberculous drugs (RFP, INH and SM) failed to reduce
      the fever or drainage from the biopsy region, the patient was transferred to our
      hospital. Chest X-ray films taken on admission revealed dilatation of the
      superior mediastinal shadow; chest CT images revealed cervical and mediastinal
      lymphadenopathy and an anterior mediastinal abscess, but no pulmonary lesion.
      About 2 months after admission, cough developed and Gaffky type 2 was detected in
      the patients sputum. Bronchoscopy and bronchography revealed a bronchomediastinal
      fistula. Forty days after the onset of cough, reticulogranular shadows were
      observed in the right upper lobe on chest X-ray films, and a diffuse
      centrilobular lesion was observed in the right upper lobe on chest CT images.
      From these clinical observations, the patient was given a diagnosis of cervical
      mediastinal lymph node tuberculosis, which had progressed to pulmonary lesion
      through a bronchial fistula due to lymphadenitis.

PMID- 10064962
TI  - [Relapsing pneumothorax secondary to thin-walled cavitary pulmonary metastasis
      from angiosarcoma of the scalp].
AB  - A 79-year-old woman was given a diagnosis of scalp angiosarcoma. Treatment with
      interleukin-2 and radiotherapy aclieved a complete response. However, a few
      months later, the patient presented with multiple thin-walled cavitary metastases
      in the right lung and pneumothorax. The pneumothorax was successfully treated but
      soon relapsed. The patient died of respiratory failure at home. Lung metastasis
      of malignant tumors should be considered one cause of relapsing pneumothorax.

PMID- 10064963
TI  - [Resection of asymptomatic infected bulla associated with pulmonary
      tuberculosis].
AB  - The patient was a 49-year-old man. A physical examination in 1995 had disclosed
      the presence of a bulla in his left lung. Chest x-ray films taken in February
      1997 disclosed niveau formation as an abnormal shadow in contact with the bulla.
      The patient was given a diagnosis of an infected bulla, and underwent an
      operation for partial resection of the S 6 portion of the left lung. The
      intracystic fluid was serous and no general bacteria or mycobacteria were
      detected. However, histopathological examination found granulation tissue
      associated with caseous necrosis and containing mycobacteria. The patient is
      currently receiving tuberculostatic agents on an outpatient basis.

PMID- 10064964
TI  - [Lung cancer accompanying sarcoidosis with diffuse myocardial involvement].
AB  - We describe an interesting case of adenocarcinoma of the lung accompanying
      sarcoidosis with diffuse myocardial involvement. A 69-year-old man had a tumor
      shadow on chest X-ray films of the right upper lung field. Bronchofiberscopy was
      performed in Jan. 1997. Because transbronchial biopsy specimens disclosed
      granuloma, the patient was treated with isoniazid, rifampicin, and streptomycin
      sulfate for tuberculosis, but did not show any improvement. In March 1997, the
      patient was examined by an ophthalmologist for blurred vision. He was given a
      diagnosis of uveitis and referred to us for evaluation because his serum ACE and
      lysozyme levels were elevated. Bronchofiberscopy was performed again, and a
      diagnosis of lung cancer accompanying sarcoidosis was made based on the findings
      of transbronchial biopsy and bronchoalveolar lavage. The disease progressed
      rapidly, and the patient died 47 days after admission. Autopsy disclosed sarcoid
      granulomas in cardiac muscle tissue and lung tissue. There have been very few
      reports on the co-existence of sarcoidosis and lung cancer, and the relationship
      between the two diseases is unclear.

PMID- 10064965
TI  - [Aging and atherosclerosis].

PMID- 10064966
TI  - [Sleep-promoting substances].

PMID- 10064967
TI  - [Ischemic heart disease].

PMID- 10064968
TI  - [Pathophysiology and treatment of elderly hypertensive patients].

PMID- 10064969
TI  - [Risk factors for sudden death during hospitalization].
AB  - To determine the risk factors for sudden deaths in hospitalized patients, 209
      patients (103 men and 106 women, age 76.7 +/- 12.6 years old, mean +/- S.D.) who
      died in 1996 were divided into two groups and their records were analyzed. One
      group, the sudden death group (SD), consisted of 16 patients who had stayed in
      the hospital for 2 weeks or more before the onset of symptoms that led to death
      within 24 hours. Those who died more than 24 hours after symptoms began were
      placed into the non-sudden death group (NSD). Fourteen patients who died within 2
      weeks of admission were not analyzed in this study. Comparing the data of the two
      groups led to the following findings. First, the major causes of death in the SD
      group were exacerbation of chronic cardiac failure (5 cases), acute cardiac
      failure (2 cases), exacerbation of chronic respiratory failure (2 cases) and
      acute respiratory failure (2 cases). Second, patients in the SD group were
      significantly older than those in the NSD group, and had significantly more
      prescriptions for digitalis. Third, patients in the SD group had higher levels of
      hemoglobin and hematocrit, lower levels of BUN and a higher cardiothoracic ratio.
      Fourth, patients in the SD group had a higher incidence of ST abnormalities and T
      wave abnormalities in their electrocardiograms. Brugada syndrome or long QT
      syndrome were not seen in either group. Taken together, these findings suggest
      that aged patients with cardiac failure and myocardial ischemia may be at higher
      risk of sudden death.

PMID- 10064970
TI  - [Role of impaired glucose tolerance in the progression of hypertension].
AB  - The present report describes the relationship between the glucose tolerance and
      hypertension surveyed in a ten-year longitudinal epidemiological study in two
      rural communities in Hokkaido, Japan. The 1972 subjects (928 men and 1044 women,
      aged 40-64, mean 51.1 +/- 7.0 years) were randomly selected in 1977 and 1978,
      underwent a 50-g oral glucose tolerance test (GTT) at the first year. The
      prevalences of borderline hypertension (BHT) and of hypertension (HT) were
      highest in those with diabetes mellitus (DM), followed by those with borderline
      diabetes (BDM) and those normal glucose tolerance (NGT). Systolic and diastolic
      blood pressure were significantly and positively correlated with plasma glucose
      levels during fasting (FPG), 60 min. after GTT (60G), and 120 min. after GTT
      (120G), and were ordered as follows: NGT < BDM < DM. The FPG, 60G and 120G plasma
      glucose levels were all significantly higher in BHT and HT than in NT. The
      prevalences of the progression to hypertension from non-hypertension over the ten
      year follow-up period were ordered as follows: NGT < BDM < DM. Glucose levels in
      progression group were higher than those in non-progression group. Multiple
      logistic regression analysis indicated that age, glucose intolerance, systolic
      blood pressure, and obesity index were significant predictors of the progression
      to hypertension. These results indicate that impaired glucose tolerance may be
      associated with hypertension, and might play a role in the development of
      hypertension.

PMID- 10064971
TI  - [Prevalence of glucose intolerance in Japan--from the National Circulatory
      Disorders Basic Survey, 1990].
AB  - The prevalence of glucose intolerance was surveyed in 8,063 people over 30 years
      old from the general population of Japan. The data used in the analysis were from
      the Fourth National Circulatory Disorders Basic Survey, which was conducted in
      1990. Survey items included history of diabetes mellitus, body mass index (BMI)
      and daily life activity. Blood and urine were also examined, and the blood
      glucose levels, presence or absence of sugar in urine, and levels of
      glycohemoglobin (HbA1c) were determined. Glucose intolerance was identified from
      the blood glucose level, HbA1c level and history of diabetes mellitus. The
      frequency of glucose intolerance was 8.6% in all subjects (11.9% in men and 6.3%
      in women). The frequency was higher in older people: 1.7 times higher in men over
      65 years old and 2.5 times higher in women over 65 years old. Among people over
      40 years old, glucose intolerance was significantly more prevalent in men than in
      women. It was also significantly more prevalent in men living in big cities than
      in men living in rural areas. Among obese male subjects and men with a low level
      of activity in daily life, the frequency of glucose intolerance was higher than
      in normal male subjects. The level of activity in daily life tended to be lower
      for people living in big cities than for those in rural areas. The results
      suggest that the prevalence of glucose intolerance depends on the environment in
      which people live. The results also indicate that raising the level of activities
      in daily life might help prevent diabetes mellitus.

PMID- 10064972
TI  - [Differences in exercise blood pressure response between dipper and non-dipper
      elderly patients with essential hypertension].
AB  - We evaluated the circadian variation and exercise stress response patterns of
      blood pressure (BP) in elderly patients with essential hypertension. Ambulatory
      BP monitoring for 48 hours every 30 minutes, and treadmill exercise test using a
      Bruce protocol at PM 3 to 5 were performed in 49 untreated patients with
      hypertension. Mean daytime (awake), and night-time (sleeping) systolic BP (SBP)
      and diastolic BP (DBP) values were analyzed by reviewing the patients' diaries,
      and the nocturnal reduction rate (NRR) of SBP and DBP were calculated according
      to the following formula. NRR (%) = [(daytime mean-nighttime mean)/daytime mean]
      x 100. The patients were divided into two groups according to the presence
      (dipper, n = 25) or absence (non-dipper, n = 24) of a reduction in both SBP and
      DBP during the night by an average of more than 10% of the daytime BP. Mean
      values of SBP and DBP measured over 48 hours in the dipper and non-dipper groups
      were similar. Responses of SBP to dynamic exercise at 2 to 5 minutes in the non
      dipper group were significantly smaller than those in the dipper group (p <
      0.05). Non-dipper patients with hypertension responded to dynamic exercise stress
      with smaller increases in SBP than did those in the dipper group. The differences
      in BP responses to exercise may affect the circadian blood pressure profile in
      dipper and non-dipper elderly patients with essential hypertension.

PMID- 10064973
TI  - [Factors that influence the serum of atrial natriuretic peptide and brain
      natriuretic peptide concentrations--is there a specific marker for senile
      patients?].
AB  - To evaluate factors that influence of atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) levels in elderly people, we measured those levels in
      54 men and 148 women (84.4 +/- 0.5 years old), and looked for associations of ANP
      and BNP with clinical factors and echocardiographic variables [left ventricular
      mass index and atrial to-early peak transmitral velocity ratio (A/E)]. ANP and
      BNP levels were 1.6 and 6.5 times higher than average. Sex was not a significant
      factor. We also looked for a link between cardiac rhythms and levels of ANP and
      BNP. Patients with atrial fibrillation had significantly higher levels of ANP and
      BNP than did patients with sinus rhythm. ANP and BNP levels were abnormally high
      in patients with left ventricular hypertrophy (LVH). We could measured A/E in 161
      of 202 subjects; 154 of 157 subjects with normal LV systolic function had A/E > 1
      which indicates abnormally low in LV diastolic function. Moreover, abnormally
      high LV diastolic stress might have been present, because 124 of 202 subjects had
      aortic regurgitation. We divided the patients into two groups: those 65 to 75
      years old, and those over 75 years old. The older patients had significantly
      higher levels of ANP and BNP even without LVH and without a difference in renal
      function. Furthermore, the older patients had significantly higher levels of BNP
      even without LVH, with normal renal function, with sinus rhythm, with normal LV
      systolic function, and in NYHA Class I or II. These data indicate that ANP and
      BNP levels in people with senility may be associated with the cardiac rhythm and
      with abnormally low renal function, myocardial hypertrophy, abnormally high
      cardiac volume, and abnormally low diastolic function.

PMID- 10064974
TI  - [Severe hypertriglyceridemia induced by tamoxifen].
AB  - A 71-year-old woman was admitted to our hospital because of severe
      hypertriglyceridemia. The patient had a 26-year history of non-insulin-dependent
      diabetes mellitus and hyperlipidemia (T-chol 300 mg/dl, TG 300 mg/dl). She was
      treated with sulfonylurea and clofibrate. Seven years before admission, she had
      undergone a radical mastectomy for cancer of the left breast. After the
      operation, she had received tamoxifen and fluorouracil. One month before
      admission, she had marked hypertriglyceridemia (triglyceride 2,106 mg/dl). After
      discontinuation of tamoxifen and fluorouracil, her serum triglyceride level
      decreased to 372 mg/dl; when tamoxifen was given again, it increased to 581
      mg/dl, and her hepatic triglyceride lipase activity decreased from 0.228 to 0.164
      mumol FFA/ml/min. Apolipoprotein E phenotype was wild type E3/3. The
      concentration of sex-hormone-binding globulin increased from 110 to 130 nmol/l.
      These changes associated with tamoxifen treatment were similar to those seen
      after administration of estrogen. Tamoxifen, an anti-estrogen, has been used as
      adjuvant therapy in cases of estrogen-receptor-positive breast cancer. Tamoxifen
      has some weak estrogenic activity. The tamoxifen-induced hypertriglyceridemia
      seen in this case was an effect of its estrogenic action.

PMID- 10064975
TI  - [Two elderly patients with intestinal perforation caused by press-through
      package].
AB  - We report two cases of intestinal perforation caused by accidental swallowing of
      Press-Through Packages (PTP). The first case occurred in a 90-year-old woman with
      moderate dementia. She was admitted to our hospital because of abdominal pain and
      intestinal obstruction. She showed symptoms and sign of peritonitis and underwent
      abdominal surgery. The postoperative diagnosis was diffuse peritonitis due to a
      perforated rectal ulcer caused by the sharp corners of an accidentally swallowed
      PTP. The second case occurred in an 82-year-old woman with recurrent symptoms and
      signs of intestinal obstruction. She underwent abdominal surgery and the
      operation revealed an ileal perforation due to penetration by the sharp edge of a
      PTP. Both patients were discharged in good condition. PTPs are rapidly becoming
      popular as packaging for tablets and capsules. However, reports of accidental
      swallowing of PTPs have recently been increasing. In most cases, the PTPs were
      found in the esophagus and removed endoscopically. Progression of accidentally
      swallowed PTPs to the intestines is rare. However, when this occurs, the
      patient's condition becomes more serious. We propose that drugs should not be
      dispensed in PTPs but rather handed to the patients, especially to elderly
      patients, or when impossible, the corners of PTPs should be rounded.

PMID- 10064976
TI  - [The role of behavioral medicine and its place in medical practice].
AB  - Behavioral medicine is a rapidly developing interdisciplinary field that
      integrates the biological and psychosocial perspectives of human behavior and
      apply them to practice of medicine. The aim of behavioral medicine is to analyse,
      prevent and treat reversible, non-adaptive behavioral patterns, reactions and
      symptoms. In the early stages of chronic non-infectious illnesses of great
      epidemiological significance reversible regulation disturbances, non-adaptive
      behavioral factors (such as smoking, alcohol abuse, etc.) are the most important
      risk factors, which are closely connected with emotional disturbances, anxiety,
      depressive symptomatology, hopelessness and learned pathological reactions.
      Behavioral medicine deals with the recognition, effective treatment and
      scientific model of these behavioral and psychological problems on different
      fields of medical practice.

PMID- 10064977
TI  - [Prognosis and invasion marker expression of cutaneous melanoma. Metastasis
      associated genes (nm23, CD44v3, MMP2].
AB  - For the evaluation of the prognosis of the melanoma malignum (MM) several markers
      have been used before but none of them was powerful enough therefore a search for
      new markers is justified. The authors have studied the expression of three
      metastasis associated proteins, nm23, CD44v3 and MMP2 collagenase using
      immunohistochemistry on the paraffin embedded tissue samples of 22 primary skin
      melanomas. The expression of these markers was independent from the thickness of
      the tumor or the clinical stage of the disease. Due to the frequent discrepancy
      between the thickness of the tumor and the actual outcome of the disease, they
      regrouped the cases according to the biological behaviour of the tumor into non
      metastatic, lymph node-metastatic and organ metastatic forms. Based on the MMP2
      expression +/- tumors can be found but the expression does not correspond to the
      biological behaviour of MM while decreased nm23 expression characterized the
      lymph node metastatic tumors. CD44v3 expression was rare in MM and occurred at
      low level, however, when expressed it showed significant correlation to the organ
      metastatic phenotype. The authors concluded that the classic invasion markers in
      case of MM have a limited potential in the characterisation of the invasive
      phenotype, therefore more sensitive markers are necessary.

PMID- 10064978
TI  - [EUROASPIRE: survey conducted by the European Society of Cardiology on secondary
      prevention of coronary disease. Hungarian results].
AB  - The European Society of Cardiology, the European Atherosclerosis Society and the
      European Society of Hypertension published in 1994 a joint statement and
      recommendation on prevention of coronary heart disease in clinical practice. The
      EUROASPIRE study intended to investigate the present clinical practice in this
      respect in 9 European countries. The present paper deals with the Hungarian leg
      of the collaborative study. Hospital data of 546 patients below the age of 70
      were reviewed of whom 29% were women. Consecutive patients were identified
      retrospectively with the following discharge-diagnoses: coronary bypass grafting,
      PTCA, acute myocardial infarction and angina pectoris. Minimum 6, in the average
      18 month after the index event, patients were interviewed and examined. The
      participation rate was 77%. During the index hospitalisation an incomplete
      documentation of the main risk factors was found: blood pressure values were
      missing in 12%, lipid values in 48%, smoking status in 34%, body weight in 22%
      and family history in 46% of the cases, with wide variation between diagnostic
      categories. At follow-up 23% of the patients were obese (BMI > or = 30 kg/m2),
      49% had elevated blood pressure (140/90 > or = Hgmm), 46% had total cholesterol
      above 5.5 mmol/l, 23% smoked and 27% were diabetic. 75% of the patients were on
      antiplatelet, 14% on anticoagulant, 58% on beta-blocking, 22% on lipid lowering,
      32% on ACE-inhibitor and 44% on calcium channel blocking medication. The
      screening of first degree relatives was recommended in only 18% of the patients.
      The results speak for a substantial neglect of secondary prevention of coronary
      patients in the Hungarian clinical practice. However without complex detection,
      evaluation and management of risk factors it is impossible to reduce the
      recurrence and high mortality of coronary heart disease.

PMID- 10064979
TI  - [Muir-Torre syndrome].
AB  - Muir-Torre syndrome patients have multiple visceral malignancies along with
      cutaneous sebaceous tumors and keratoacanthomas. We describe a history of a 64
      year-old male patient with 13 tumours, who survived 13 years. The initial
      ascending colon adenocarcinoma was followed by some different tumors of the skin:
      adenoma and carcinoma of sebaceous glands, epidermoid and basaloid carcinoma and
      other benign tumors. The last time developed rectal adenocarcinoma was operated.

PMID- 10064980
TI  - [The use of the temporal fascia pedicle flap for the reconstruction of the
      posterior wall in the external auditory meatus and osteovit obliteration of the
      mastoid process in the surgical treatment of chronic cholesteatoma in otitis
      media].
AB  - The authors present the results of the treatment of 34 patients with chronic
      cholesteatomatous otitis media in whom the posterior wall of the external
      auditory meatus was reconstructed by remodelling the pedicel flap of the temporal
      fascia and by obliterating the mastoid process with Osteovit. The results of the
      operation were estimated with reference to the time of the postoperative cavity
      getting dry and compared with the control group of individuals in whom radical
      conservative operation was performed. The results proved that the
      epithelialization time was distinctly shorter and neither granulation nor
      otorrhea appeared during 24 months' observation.

PMID- 10064981
TI  - [Pathological and clinical assessment of polypoid hypertrophy of the vocal
      cords].
AB  - Polypoid hypertrophy of mucosa of the vocal cord is the most common non
      neoplastic disease of the larynx. This hypertrophy has a form of simple polyp of
      vocal cord or polypoid hypertrophy of the whole length of one or both vocal
      cords. In most cases a course of the disease is typical. In a few cases we can
      observe changes in polyp epithelium, i.e. hyperplasia or even dysplasia. Clinical
      and histological analysis of 809 patients treated because of laryngeal polyps (by
      Kleinsasser microsurgical procedure) within the period of 1981-1995 at ENT Clinic
      in Gdansk was made. Sex and age of the patients, macroscopic picture of the
      disease as well as treatment and results were assessed. Special attention was
      paid to the problem of polyp epithelium rebuilding. In a few cases, polyp of the
      vocal cord should be assessed as praecancerous state.

PMID- 10064982
TI  - [Gastrointestinal cancer antigen and immunoglobulins G, A, M in patients with
      head cancer].
AB  - The authors present the results of examinations of immunoglobulins A, G, M serum
      concentrations and of a sensitivity of test of biochemical tumor marker (Ca 19-9)
      in a group of 35 patients with head malignant tumors. There was a statistically
      significant increase of immunoglobulins IgA, IgG and decrease of immunoglobulin
      IgM. We observed statistical correlation between serum concentrations of IgA, IgG
      and serum concentrations of IgA, IgM. The sensitivity of Ca 19-9 was 23% in the
      preliminary study. The values of Ca 19-9 changed in monitoring of tumors to 26%.
      There was a statistically significant correlation between sensitivity of Ca 19-9
      and serum concentration of IgM. We did not observe any statistical correlation
      between Ca 19-9 and the age of patients.

PMID- 10064983
TI  - [Fat tissue in the treatment of tympanic membrane perforations].
AB  - Adipose myringoplasty is presented as a simple and effective technique in
      managing tympanic membrane perforations. A review of 34 fat plug myringoplasties
      performed in 28 patients with drum perforations over a 4-year period was done.
      Twenty-two myringoplasties were postinflammatory, five--posttraumatic and three-
      postinflammatory in temporalis fascia. Criteria for selection, operative
      technique and results are discussed.

PMID- 10064984
TI  - [Fibrosarcoma of the larynx].
AB  - Fibrosarcoma is the most common neoplasm of the larynx of mesenchymal origin.
      Between 1991 and 1996 three cases of fibrosarcoma were observed in the ENT Clinic
      of the Pomeranian Medical Academy. There were two males and one female aged 49
      66. It makes 0.5% (3 in 655 cases) of all malignant neoplasms of the larynx
      treated by surgery in the mentioned period of time. The primary focus of the
      neoplasm in one case was located in anterior commissure and in the two others--in
      the vocal cord. In all the cases surgery was done. Results of the treatment were
      given.

PMID- 10064985
TI  - [Pedicled parietal bone grafts in the facial reconstruction surgery].
AB  - Between years 1996 and 1997, pedunculated parietal bone graft for facial
      reconstruction after tumor excision was used in 8 patients. The defects comprised
      one side of maxilla with the orbit bottom, zygomatic bone and the orbit bottom,
      mandibular ramus, and the whole mandible: in 4, 1, 2, and 1 patient respectively.
      The reconstruction was done directly after tumor excision in 6 patients and later
      on in the other 2. The grafts were of full thickness in 6 and of outer table in
      2. Functional and cosmetic effects were considered satisfactory in 6 patients.
      The whole mandible reconstruction ended up with a failure due to infection and
      tumor recurrence.

PMID- 10064986
TI  - [The results of radiation and surgical treatment of early vocal cord carcinoma
      (T1a, T1b)].
AB  - Results of surgery treatment from the external access and radiotherapy in early,
      stage of vocal cords carcinoma were presented. Clinical material consisted of 94
      cases with squamous cell carcinoma of vocal cords with stage T1a and T1b treated
      in Szczecin University Department of Otorhinolaryngology from 1987 to 1996. 51
      cases were operated on (26 by chordectomy and 25 by frontolateral laryngectomy).
      Radiotherapy was applied in 43 patients. The 3 and 5 years' survival rate in the
      surgery group was 97% and after radiotherapy 88 to 80%. The functional results
      were also presented. It was concluded that the mode of treatment in early stages
      of vocal cord carcinoma should be individualized.

PMID- 10064987
TI  - [Foreign bodies in the lower respiratory tract: experience based on materials
      gathered in the ENT department of the Poznan Higher School of Medical Sciences
      between 1945 and 1997].
AB  - 258 foreign bodies were removed from the lower respiratory tract in ENT
      Department of Poznan High School of Medical Sciences between 1945 and 1997. The
      age ranged from 0 to 85 years, but the most numerous group (68%) was found
      between 0 and 10 years. 86.5% patients were admitted to hospital during first
      three days after inserting the foreign body. The longest time of foreign body
      existence inside the bronchus was a period of 18 years. The most often met
      foreign bodies were: bones, bean seeds, fruit stones, pieces of food, iron nails.
      Spontaneous evacuation of the foreign body took place in 4% of cases. 98% of
      foreign bodies were removed by means of rigid bronchoscopy. Bronchofiberoscopy
      was performed for diagnostic purposes or for taking out foreign bodies located in
      the peripheral parts of the bronchial tree. 3% of patients were referred to the
      further toracosurgery treatment.

PMID- 10064988
TI  - [Cochleostomy during the intracochlear implantation. Anatomical conditions in
      children and adults].
AB  - Cochleostomy is an opening of the perilymphatic spaces of the cochlea. It is the
      most important moment in intracochlear implant surgery. There are contradictory
      opinions in the available literature regarding this surgical intervention.
      Cochleostomy is performed through the round window, the oval window, the
      promontory or through the apical turn of the cochlea. A microanatomical study was
      performed to evaluate which kind of cochleostomy would be most effective and safe
      for the main structures of the temporal bone. The distances between round window
      and round window niche structures, the jugular bulb, internal acoustic meatus,
      posterior semicircular canal, internal carotid artery and cochlear canalicule
      were measured. It was stated that all the dimensions were smaller in children of
      up to four years of age and the differences were statistically significant.
      Cochleostomy through the promontory, especially using the "soft" technique of
      endosteum opening is safe for all the structures, and in children it also
      protects the cochlear canalicule.

PMID- 10064989
TI  - [Voice acoustic analysis in patients with a hearing aid or cochlear implant].
AB  - The subject of our study was two groups of patients with hearing disorders: 23
      cases implanted with multi-channel cochlear device (Nucleus Mini System 22) and
      10 patients with perceptive hypoacusis who used hearing aids. The voice acoustic
      analysis was performed before cochlear implantation or application of a hearing
      aid and after a 6-month rehabilitation period. The acoustic analysis was carried
      out by means of a laryngophone connected to KAY 4300 instrument. The estimation
      of acoustic parameters of a laryngeal tone during rehabilitation process as well
      as parameters of spectrographic analysis was presented with the use of MDVP and
      CSL. Voice acoustic analysis can be an objective evaluation of progress in voice
      and speech rehabilitation process of patients with hearing disorders,
      particularly small children.

PMID- 10064990
TI  - [Comparative analysis of surgical approaches used during intracochlear
      implantation with reference to their safety for the important structures of the
      temporal bone].
AB  - A comparative analysis was made of three operative approaches used in cochlear
      implantations, regarding their safety for main structures of the temporal bone,
      simplicity and versatility. Anatomical and clinical data from literature were
      worked out. It was stated that the posterior tympanotomy approach is best because
      of its allows for good view on the round window niche and its risk for the facial
      nerve damage is not greater than that of the other routes. The posterior
      tympanotomy approach is safe for small children because the space between the
      facial nerve and tympanic ring is not smaller in them than in adults. This route
      to the tympanic cavity creates also possibilities for widening of the operating
      area if it is necessary, for example in obstructed and obliterated cochleas. The
      anterior tympanotomy approach is dangerous for children because of a great risk
      for facial nerve and jugular bulb. The mastoidotomy-tympanotomy approach is on
      the other hand very complex, requires special equipment and is not more
      protective for the facial nerve than posterior tympanotomy approach.

PMID- 10064991
TI  - [The results of sudden deafness treatment].
AB  - In years 1980-1994, 180 sudden hearing loss cases were diagnosed and treated.
      Sudden deafness is a symptom of a variety of diseases. Time is often the most
      important factor in the overall recovery. However the etiology was difficult to
      identify, precise examinations permitted to determine the probable diagnosis and
      to apply appropriate treatment. In cases with expected vascular etiology
      Nimodypine was additionally employed with good results. The most frequent reason
      for sudden hearing loss was vascular factors (50%), next viral infections (25%),
      acoustic trauma (10%), allergy (5%), and unknown causes (10%). The best results
      were obtained in the patients under treatment between 1 and 7 days of sudden
      deafness persistence. Remarkably better results were received in cases of sudden
      deafness concerning wide frequency band than in those within high tones only.

PMID- 10064992
TI  - [Hearing aid fitting in children treated at the Phoniatric Outpatient Clinic in
      Zabrze in years 1986-1990].
AB  - The purpose of this study was to evaluate the hearing aid fitting of 179
      regularly controlled, hearing-disabled children from the Silesian area, first
      time admitted to Phoniatric Outpatient Clinic in Zabrze in years 1986-1990. The
      mean age of provision of a hearing aid was high. Children were supplied with
      hearing aids at mean age of 4,9 years (losses > 60 dB) and of 9,3 years (losses <
      or = 60 dB). There was a delay from 8,4 up to 12,5 months (losses < or = 60 dB)
      between the age of fitting and the issue of the hearing aid. It was also stated
      that the total amount of children wearing their aids binaurally decreased
      significantly from 118 to 74 during 5 years' period. As for the utilisation of
      hearing aids, prevalence of full-time users (57.9%) was demonstrated in
      confrontation to non-users (5.6%).

PMID- 10064993
TI  - [Special schools for deaf children. Their status of hearing, speech and clinical
      history].
AB  - 170 deaf school children were described with respect to the following conditions:
      depth of the hearing impairment, phonic speech ability and lip reading
      possibility. The anamnesis data were also analyzed. All children disclosed a
      profound hearing impairment. 60 from 170 (35%) had deaf parents. The phonic
      speech ability was possessed in an unsufficient degree by only 128 (75%)
      children. 69 (40%) children passed 3 years of speech and hearing rehabilitation
      before entering the school. 58 (34%) showed good lip reading ability.

PMID- 10064994
TI  - [Pleomorphic adenoma of the parapharyngeal space: a case report].
AB  - The authors described a case of parapharyngeal space pleomorphic adenoma in a 22
      year-old patient. The excision of the tumor through the mouth, without cutting up
      the jaw bone, turned out safe and radical.

PMID- 10064995
TI  - [Sarcoidosis of the paranasal sinuses].
AB  - The authors described diagnostics difficulties, clinical features and treatment
      of this disease. The treatment is insufficient, but only interventional, although
      the clinically dominating symptoms may be due to a chronic disease inside of the
      sinuses and they are known to be caused by specific disorders in immunology.
      Immunosuppression, using prednisone, and reestablishing sinus ventilation and
      drainage via natural ostia is the basis of treatment, but it does not lead to
      recovery. Two rare cases of paranasal sinuses sarcoidosis are described.

PMID- 10064996
TI  - [A rare case of metastatic tumor in the neck with unknown primary focus].
AB  - The authors present a rare case of metastatic tumor in lymphoid gland in the neck
      without primary identification of the cancer. The authors discussed the clinical
      picture, as well as diagnostic and therapeutic procedures.

PMID- 10064997
TI  - [The organization and activity of the otolaryngological institutions in Warsaw in
      the second half of the 19th century and at the beginning of the 20th century].
AB  - The importance of various otolaryngological institutions: hospital wards,
      outpatient clinics, infirmaries and consulting rooms in the formation of the new
      specialization, otolaryngology, is described in this paper. An important role of
      surgery in the first period of the development of otolaryngology is mentioned. At
      that time all major otolaryngological operations were performed by general
      surgeons. The necessity to create new separate hospital otolaryngological wards
      became evident. The attainment of general surgical education and management of
      suitable post-operation treatment by otolaryngologists as well as creation of
      autonomous operating rooms were also evident. Poor state of Warsaw
      otolaryngological outpatient clinics is described in detail. The state of
      otolaryngological institutions in Europe, in the United States of North America
      and in the Kingdom of Poland is described briefly.

PMID- 10064998
TI  - [The participation of the Warsaw otolaryngologists in medical conferences and
      congresses in the 19th century].
AB  - The participation of a famous Polish laryngologist Teodor Heryng (1847-1925) in
      many scientific congresses was presented in separate publications. Many Varsovian
      otolaryngologists also took part in a great number of international congresses.
      Jan Sedziak's (1861-1932) participation in international congress in Vienna in
      1908 on account of the 50th anniversary of the invention of laryngoscopy by
      Manuel Garcia is stressed. Sedziak was specially esteemed in Great Britain and in
      the United States of North America. Very significant contribution of Alfred M.
      Sokolowski (1849-1924) to the medical congress in Rome in 1894 is described. The
      widespread contacts of Varsovian otolaryngologists: Zdzislaw Dmochowski, Feliks
      Erbrich, Leopold Lubliner, Edmund Modrzejewski, Zygmunt Srebrny. Jan Szmurlo,
      Witold Szumlanski with the European scientific world are mentioned, as well as
      their active participation in many medical meetings and congresses.

PMID- 10064999
TI  - [A new water manometer for the measurement of pressure during swallowing].
AB  - A new pneumohydraulic water manometer for measuring pressure generated in the
      pharynx and oesophagus during swallowing was presented. It consists of measuring
      and pneumatic parts and a computer.

PMID- 10065000
TI  - [The significance of synaptic neurotransmitters on the acquisition and retention
      of vestibular habituation].

PMID- 10065001
TI  - [Obituary to Jakub Jan Biber, MD].

PMID- 10065002
TI  - [Obituary to Stanislaw Michalowski, MD (1914-1995)].

PMID- 10065003
TI  - [Why has the International Center of Childhood been murdered?].

PMID- 10065004
TI  - [An example of how to measure the relation between developmental dyslexia and
      illiteracy].
AB  - The ability to read and the phonological fitness of 89 youth (average age of 21.3
      years) having difficulty with social and professional integration were examined.
      We observed that 64% of them (n = 57) had difficulty in reading. The results of
      the phonological and reading tests showed that developmental dyslexia
      constitutes, for 56% of the subjects (n = 32), or for 36% of the population of
      youth with difficulties, the explanatory framework for the delay of acquisition
      of these capacities. Reading difficulties for these youth were significantly
      linked to an alteration of the phonological treatment that effects: short-term
      verbal memory, auditory discrimination and meta-phonological fitness. The data
      tends to validate the hypothesis of the existence of a functional link between
      developmental dyslexia and illiteracy.

PMID- 10065005
TI  - [Health and environment in Villeurbanne. Opinions of the population].
AB  - The interactions between health and the environment are at the heart of the
      concerns of the political actors in Villeurbanne. Their participation in the
      network "Villes-Sante" and the adoption of the Municipal Plan for the
      Environment, has incited them to promote a local approach based on the
      identification of the health problems linked to the environment that are
      expressed and felt by the inhabitants. The study, carried out among 567
      individuals (1/150 of the inhabitants of Villeurbanne), showed that overall, 73%
      complain of two important environmental problems linked to their state of health:
      air pollution (48% of inhabitants), and noise (district noise 37%, and noise from
      the neighbours 24%). Traffic is the main source of these urban nuisances. Despite
      this, the environment is not very important in the minds of many people (36.5%)
      when compared to unemployment (68.1%), drugs (48.5%), and violence (58%).

PMID- 10065006
TI  - [The essential drugs program in Haiti].
AB  - A survey was carried out by random sample among institutions that had benefited
      from the programme of humanitarian assistance during the period of economic
      embargo imposed in Haiti. The objective of this survey was to determine the
      effect that the distribution of medicines during this period had on the
      reactivation of the programme for essential drugs. Of the 51 health institutions
      selected, 45 provided satisfactory information. The results show that 42
      institutions received medicines from the humanitarian aid programme. Six months
      after the end of the programme for humanitarian assistance, 39 of these
      institutions were using essential drugs in dispensaries and in health centres
      without beds. Essential drugs predominated over special medicines. These
      institutions continued to stock up at the PROMESS centre for essential drugs.
      This institution, initially created for the programme for humanitarian
      assistance, continued to function in October, 1994, a year after the end of the
      programme, and became the object of the adaptation of long-term support for
      programmes of the national health plan. The study also showed that the recovery
      of costs of medicines is a current practice within 44 of the 45 institutions
      surveyed, no matter whether their status is public, private, or mixed, thus
      emphasising the availability of the community for participating in financing
      health services. These results show that the humanitarian assistance programme,
      through the distribution of medicines and independently of its specific
      objectives, reinforced the programme for essential drugs. This is an indication
      that humanitarian assistance programmes may not only carry out their objectives,
      which are often limited and short-term, but may also produce lasting results that
      favour the reinforcement of development structures.

PMID- 10065007
TI  - [Determinants for choice of medical management in the Bas-Rhin].
AB  - It has already been established that the social origin and the demographic
      factors have an influence, among other things, on medical practice. What about it
      in the Bas-Rhin? Our survey's objective consists of emphasising on what motivates
      the choice of the type of medicine. METHOD: Phone survey on a representative
      sample of 1010 persons aged between 25 and over 64, residing in the Bas-Rhin.
      RESULTS: Participation has been of 66.3%. Among participants, there are 49.1% of
      men and 50.9% of women. 9 among 10 participants state that they have a family
      doctor. More women claim they are more likely to see a homeopathic doctor and/or
      a professional of alternative medicine. 8 among 10 persons have their blood
      pressure checked. 50.9% of participants have a blood analysis made in order to
      determine their cholesterol level. Building on these medical practices, several
      groups have been created. 54.1% of participants belong to the same group, having
      in common the facts of having a family doctor, having their blood pressure
      checked, and never seeing a professional of alternative medicine. The female
      participants are properly followed up on the gynecological point of view. Only 29
      among 500 women have never had a cervical smear done. The carrying out of a
      mammography raises with age. When fearing a potential cancer, the first step
      taken by 56.2% of participants consists of seeing a generalist doctor, whereas
      65.9% would prefer going to the hospital to perform further tests. As far as
      treatment is concerned, 76.8% of them would rather go to a specialised
      department, even if it is located far from their home. Special attention is to be
      paid to the fidelity of the population of the Bas-Rhin toward their family
      doctor. He represents the main link of information between the patient and the
      prevention policies that have been implemented over the last years.

PMID- 10065008
TI  - [A cardiovascular health promotion program for 9-12 year old children and the
      community of Saint-Louis du Parc/Quebec].
AB  - This article presents a programme for cardiovascular health for 9 to 12 years old
      children, called "Healthy Heart" Saint-Louis du Parc and carried out in low
      socioeconomic and multiethnic part of Montreal, Quebec, Canada. These five years
      programme targets were more both spheres: school and community (leisure centre,
      ethnocultural centre, groceries and other places). We develop the objectives, the
      conceptual models underlying to the programme, the perspective of work, the
      infrastructure of the programme: its staff and financing, the partnerships and
      the structure organising. Then we present the various interventions carried out
      along the period and so a description of many evaluations. At last, we discuss
      about the programme continuation.

PMID- 10065009
TI  - [Occupational medicine in Morocco: analysis of practices and proposition of
      action].
AB  - With the aim of a better knowledge of their activities of training and
      information of workers, a survey has been conducted through questionnaires sent
      to 582 occupational health physicians in Morocco. Among the 48% of physicians who
      accepted to answer the questionnaire, over half was effectively working in
      companies. This study revealed many problems in prevention of professional
      hazards. Workers information about professional risks and measures of prevention
      was systematically given by 56% of physicians during pre-employment examination
      and 51% during systematic visit. During "third time", 49% of physicians were
      informing workers of professional risks and 54% of measures of prevention. With
      regards to meetings of information, only 26% of physicians were organising such
      meetings and teaching workers first aid. Consequently, we propose the
      implementation of protocols "Safety in companies". Informing and teaching the
      workers about safety, are the mandatory first steps to reduce and prevent
      professional diseases and accidents; occupational medicine, despite various
      obstacles should promote it.

PMID- 10065010
TI  - [Health education in school].

PMID- 10065011
TI  - [Air pollution and its management: the responses that will determine the future
      that we want for ourselves and our children].

PMID- 10065012
TI  - Practical wisdom.

PMID- 10065013
TI  - The (un)regulation of dietary supplements.

PMID- 10065014
TI  - Implementation of substance use screening in prenatal clinics.
AB  - BACKGROUND AND OBJECTIVES: To reduce women's consumption of alcohol and other
      drugs during pregnancy, the Department of Epidemiology for the Aberdeen Area
      Indian Health Service (AAIHS) promoted a maternal substance use screening program
      for prenatal clinics in 1992. This report describes the adherence to the
      screening protocol at AAIHS facilities and barriers to such screening. METHODS:
      Prenatal clinic staff members at 20 AAIHS health care facilities were surveyed to
      determine the extent of prenatal substance use screening and the barriers to its
      implementation. The medical records of a random sample of 235 women who sought
      prenatal care at five hospitals were reviewed to determine whether prenatal
      clinic staff adhered to the screening protocol. RESULTS: Of the 20 health care
      facilities, 13 (65%) had implemented the screening. The major barriers to
      implementing screening were lack of training in prenatal substance use screening
      and lack of clinic staff designated to administer the screening protocol. Though
      not statistically significant, our data suggest that women not administered the
      screening questionnaire were more likely to be multiparous (prevalence ratio =
      2.1; 95% confidence interval = 0.9, 4.5). CONCLUSIONS: To improve screening of
      pregnant women for substance use, prenatal clinic staff members should address
      administrative barriers and assess adherence of health care providers and
      patients to the screening protocol. Training of prenatal clinic personnel is
      essential to implement optimal maternal substance use screening in prenatal
      clinics.

PMID- 10065015
TI  - American Roentgen Ray Society 99th annual meeting. New Orleans, Louisiana, USA.
      May 9-14, 1999. Abstracts.

PMID- 10065016
TI  - Atrial fibrillation: towards an understanding of initiation, perpetuation, and
      specific treatment.

PMID- 10065017
TI  - Imaging the heart in adult congenital heart disease.

PMID- 10065018
TI  - Cardiovascular problems in divers.

PMID- 10065019
TI  - Coronary pressure measurement and fractional flow reserve.

PMID- 10065020
TI  - Cholesterol lowering and coronary artery disease: mechanisms of risk reduction.

PMID- 10065021
TI  - Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in
      hypertrophic cardiomyopathy with late congestive heart failure.
AB  - OBJECTIVE: To investigate the possible coexistence of mitochondrial DNA (mtDNA)
      mutations in patients with beta myosin heavy chain (beta MHC) linked hypertrophic
      cardiomyopathy (HCM) who develop congestive heart failure. DESIGN: Molecular
      analysis of beta MHC and mtDNA gene defects in patients with HCM. SETTING:
      Cardiovascular molecular diagnostic and heart transplantation reference centre in
      north Italy. PATIENTS: Four patients with HCM who underwent heart transplantation
      for end stage heart failure, and after pedigree analysis of 60 relatives, eight
      additional affected patients and 27 unaffected relatives. A total of 111
      unrelated healthy adult volunteers served as controls. Disease controls included
      an additional 27 patients with HCM and 102 with dilated cardiomyopathy.
      INTERVENTION: Molecular analysis of DNA from myocardial and skeletal muscle
      tissue and from peripheral blood specimens. MAIN OUTCOME MEASURES: Screening for
      mutations in beta MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing
      gradient gel electrophoresis or single strand conformational polymorphism
      followed by automated DNA sequencing. RESULTS: One proband (kindred A) (plus
      seven affected relatives) had arginine 249 glutamine (Arg249Gln) beta MHC and
      heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred
      B) with sporadic HCM had identical mutations. The remaining two patients (kindred
      C), a mother and son, had a novel beta MHC mutation (lysine 450 glutamic acid)
      (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)-->leucine
      (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount
      of mutant mtDNA was higher in the myocardium than in skeletal muscle or
      peripheral blood and in affected patients than in asymptomatic relatives.
      Mutations were absent in the controls. Pathological and biochemical
      characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and
      B) were identical, but different from those of the two patients with Lys450Glu
      plus T9957C(Phe-->Leu) mutations (kindred C). Cytochrome C oxidase activity and
      histoenzymatic staining were severely decreased in the two patients in kindreds A
      and B, but were unaffected in the two in kindred C. CONCLUSIONS: beta MHC gene
      and mtDNA mutations may coexist in patients with HCM and end stage congestive
      heart failure. Although beta MHC gene mutations seem to be the true determinants
      of HCM, both mtDNA mutations in these patients have known prerequisites for
      pathogenicity. Coexistence of other genetic abnormalities in beta MHC linked HCM,
      such as mtDNA mutations, may contribute to variable phenotypic expression and
      explain the heterogeneous behaviour of HCM.

PMID- 10065023
TI  - Stamps in cardiology. Heart foundations on stamps (1).

PMID- 10065022
TI  - Prevalence of hibernating myocardium in patients with severely impaired ischaemic
      left ventricles.
AB  - OBJECTIVE: Severe impairment of left ventricular (LV) contraction is associated
      with an adverse prognosis in patients with ischaemic heart disease.
      Revascularisation may improve the impaired LV contraction if hibernating
      myocardium is present. The proportion of patients likely to benefit from this
      intervention is unknown. Therefore, the prevalence of hibernating myocardium in
      patients with ischaemic heart disease and severe impairment of LV contraction was
      assessed. DESIGN: From a consecutive series of patients undergoing coronary
      angiography for the investigation of chest pain or LV impairment, all patients
      with ischaemic heart disease and an LV ejection fraction (LVEF) < or = 30% were
      identified. These patients underwent positron emission tomography (PET) to detect
      hibernating myocardium, identified by perfusion metabolism mismatch. SETTING: A
      teaching hospital directly serving 500,000 people. RESULTS: Of a total of 301
      patients, 36 had ischaemic heart disease and an LVEF < or = 30%. Twenty-seven
      patients had PET images, while nine patients were not imaged because of emergency
      revascularisation (three), loss to follow up (one), inability to give consent
      (four), and age < 50 years (one, ethics committee guidelines). Imaged and non
      imaged groups were similar in LV impairment, demographic characteristics, and
      risk factor profile. Fourteen patients (52% of the imaged or 39% of all patients
      with ischaemic heart disease and LVEF < or = 30%) had significant areas of
      hibernating myocardium on PET. CONCLUSION: It is possible that up to 50% of
      patients with ischaemic heart disease and severely impaired left ventricles have
      hibernating myocardium.

PMID- 10065024
TI  - Echo derived variables predicting exercise tolerance in patients with dilated and
      poorly functioning left ventricle.
AB  - OBJECTIVE: To determine whether resting echo derived measurements predict
      exercise tolerance and its interrelation with heart rate response and ventilation
      drive in patients with systolic left ventricular disease. DESIGN: Prospective
      echocardiographic examination followed by cardiopulmonary exercise testing.
      SETTING: A tertiary referral centre for cardiac diseases. SUBJECTS: 21 patients
      (11 with coronary artery disease, 10 with idiopathic dilated cardiomyopathy) with
      end diastolic dimension > 6.4 cm, shortening fraction < 25%, and in sinus rhythm.
      There were 11 age matched normal controls. RESULTS: In the patients, peak oxygen
      consumption (mVo2) correlated with right ventricular long axis excursion (r =
      0.62); 65% of the variance in mVo2 was predictable using a multivariate model
      with right ventricular long axis excursion and peak lengthening rate, and peak
      mitral atrial filling velocity as independent variables. Aetiology was not an
      independent predictor, although the right ventricular long axis excursion (mean
      (SD)) was greater in patients with idiopathic dilated cardiomyopathy than in
      those with coronary artery disease (2.4 (0.5) cm v 1.6 (0.5) cm, p < 0.001). Peak
      heart rate correlated with duration of mitral regurgitation (r = -0.52) and the
      slope of ventilation against CO2 production correlated with M mode isovolumic
      relaxation time (r = 0.61). CONCLUSIONS: In patients with systolic left
      ventricular dysfunction, more than half the variance in exercise tolerance can be
      predicted by factors measured on echocardiography at rest, particularly right
      ventricular long axis excursion.

PMID- 10065025
TI  - Prognostic value of ECG findings for total, cardiovascular disease, and coronary
      heart disease death in men and women.
AB  - OBJECTIVE: To study abnormalities in the resting ECG as independent predictors
      for all cause, cardiovascular disease (CVD), and coronary heart disease (CHD)
      mortality in a population based random sample of men and women, and to explore
      whether their prognostic value is different between sexes. DESIGN AND SUBJECTS:
      An age and sex stratified random sample was selected from the total Belgian
      population aged 25 to 74 years. Baseline data were gathered and resting ECGs were
      classified according to Minnesota code criteria. The sample was then followed for
      at least 10 years with respect to cause specific death. Results are based on
      observations from 5208 men and 4746 women free from prevalent CHD at the start of
      the follow up period. RESULTS: Although the prevalence of major abnormalities in
      general was comparable between sexes, women had more ischaemic findings, ST
      segment changes, and abnormal T waves on their baseline ECG, while men showed
      more arrhythmias, bundle branch blocks, and left ventricular hypertrophy. Fitting
      the multiplicative effect on subsequent mortality between all ECG classifications
      under study and sex indicated that the prognostic value of ECG changes was equal
      in women and men. Independently of other risk factors and other major ECG
      changes, almost all ECG classifications were significantly related to all cause,
      CVD, and CHD mortality. The most predictive ECG findings for CVD death were ST
      segment depression (risk ratio (RR) 4.71), major ECG findings (RR 3.26), left
      ventricular hypertrophy (RR 2.79), bundle branch blocks (RR 2.58), T wave
      flattening (RR 2.47), ischaemic ECG findings (RR 2.35), and arrhythmias (RR
      2.15). The prognostic value of major ECG findings for CVD and CHD death was more
      powerful than well established cardiovascular risk factors. CONCLUSIONS:
      Abnormalities in the baseline ECG are strongly associated with subsequent all
      cause, CVD, and CHD mortality. Their predictive value was similar for men and
      women.

PMID- 10065026
TI  - Platelet aggregation and incident ischaemic heart disease in the Caerphilly
      cohort.
AB  - BACKGROUND: Platelets are involved in myocardial infarction but evidence of
      prediction of infarction by measures of platelet function are sparce. METHODS:
      Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded
      for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results
      from 364 men were excluded, 80 of whom had not fasted before venepuncture; most
      of the others were excluded because antiplatelet medication had been taken
      shortly before the platelet tests. During the five years following the platelet
      tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health
      Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of
      platelet aggregation was found to be significantly predictive of incident IHD.
      The possibility that platelet function is predictive for only a limited time
      after it is characterised, and that prediction falls off with time, was tested.
      When IHD events are grouped by their time of occurrence after aggregation had
      been measured, the test results show a gradient suggestive of prediction of early
      IHD events. Thus, 24% of the men who had an event within 500 days of the test had
      had a high secondary response to ADP while only 12% of those whose IHD event had
      been 1000 or more days after the test had shown a high platelet response at
      baseline. The trend in these proportions is not significant. CONCLUSIONS:
      Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in
      the Caerphilly cohort study. No measure of aggregation was found to be predictive
      of IHD.

PMID- 10065027
TI  - Extent and severity of atherosclerotic involvement of the aortic valve and root
      in familial hypercholesterolaemia.
AB  - OBJECTIVE: To compare the frequency of valvar and supravalvar aortic stenosis in
      homozygous and heterozygous familial hypercholesterolaemia (FH). DESIGN: Analysis
      of life time cholesterol exposure and prevalence of aortic atherosclerosis in 84
      consecutive cases attending a lipid clinic. SETTING: A tertiary referral centre
      in London. PATIENTS: Outpatients with FH (six homozygous, 78 heterozygous).
      INTERVENTIONS: Maintenance of lipid lowering treatment. MAIN OUTCOME MEASURES:
      Calculated cholesterol x years score (CYS) and echocardiographic measurement of
      aortic root diameter, aortic valve thickness, and transaortic gradient. RESULTS:
      Four homozygotes with a mean (SD) CYS of 387 (124) mmol/1 x years had severe
      aortic stenosis (treatment started after seven years of age), whereas the other
      two had echocardiographic evidence of supravalvar thickening but no aortic valve
      stenosis (treatment started before three years of age). On multivariate analysis,
      mean transaortic gradient correlated significantly with CYS (mean = 523 (175)
      mmol/1 x years) in heterozygotes (p = 0.0001), but only two had severe aortic
      valve and root involvement. CONCLUSIONS: In patients with familial
      hypercholesterolaemia, aortic stenosis is common in homozygotes, and aortic root
      involvement is always present despite the lower CYS than in heterozygotes. It
      appears to be determined by short term exposure to high cholesterol
      concentrations in early life. Conversely, aortic root and valve involvement are
      rare in heterozygotes and occur only with severe, prolonged
      hypercholesterolaemia, possibly accelerating age related degenerative effects.

PMID- 10065028
TI  - Images in cardiology. "Steam iron" appearance of chronic thoracic aortic
      dissection on angiography.

PMID- 10065029
TI  - Results of three to 10 year follow up of balloon dilatation of the pulmonary
      valve.
AB  - BACKGROUND: The results of immediate and short term follow up of balloon
      dilatation of the pulmonary valve have been well documented, but there is limited
      information on long term follow up. OBJECTIVE: To evaluate the results of three
      to 10 year follow up of balloon dilatation of the pulmonary valve in children and
      adolescents. SETTING: Tertiary care centre/university hospital. DESIGN:
      Retrospective study. METHODS AND RESULTS: 85 patients (aged between 1 day and 20
      years, mean (SD) 7.0 (6.4) years) underwent balloon dilatation of the pulmonary
      valve during an 11 year period ending August 1994. There was a resultant
      reduction in the peak to peak gradient from 87 (38) to 26 (22) mm Hg. Immediate
      surgical intervention was not required. Residual gradients of 29 (17) mm Hg were
      measured by catheterisation (n = 47) and echo Doppler (n = 82) at intermediate
      term follow up (two years). When individual results were scrutinised, nine of 82
      patients had restenosis, defined as a peak gradient of 50 mm Hg or more. Seven of
      these patients underwent repeat balloon dilatation of the pulmonary valve: peak
      gradients were reduced from 89 (40) to 38 (20) mm Hg. Clinical evaluation and
      echo Doppler data of 80 patients showed that residual peak instantaneous Doppler
      gradients were 17 (15) mm Hg at long term follow up (three to 10 years, median
      seven), with evidence for late restenosis in one patient (1.3%). Surgical
      intervention was necessary to relieve fixed infundibular stenosis in three
      patients and supravalvar pulmonary stenosis in one. Repeat balloon dilatation was
      performed to relieve restenosis in two patients. Actuarial reintervention free
      rates at one, two, five, and 10 years were 94%, 89%, 88%, and 84%, respectively.
      Pulmonary valve regurgitation was noted in 70 of 80 patients at late follow up,
      but neither right ventricular dilatation nor paradoxical interventricular septal
      motion developed. CONCLUSIONS: The results of late follow up of balloon
      dilatation of the pulmonary valve are excellent. Repeat balloon dilatation was
      performed in 11% of patients and surgical intervention for subvalvlar or
      supravalvar stenosis in 5%. Most patients had mild residual pulmonary
      regurgitation but right ventricular volume overload was not required. Balloon
      dilatation is the treatment of choice in the management of moderate to severe
      stenosis of the pulmonary valve. Further follow up studies should be undertaken
      to evaluate the significance of residual pulmonary regurgitation.

PMID- 10065030
TI  - Increased orthostatic tolerance following moderate exercise training in patients
      with unexplained syncope.
AB  - OBJECTIVE: To determine whether a programme of simple, moderate exercise training
      increases blood volume and improves orthostatic tolerance in patients with
      attacks of syncope or near syncope related to orthostatic stress. DESIGN: An open
      study in 14 patients referred with unexplained attacks of syncope, who were shown
      to have a low tolerance to an orthostatic stress test. Measurements were made of
      plasma and blood volumes, orthostatic tolerance to a test of combined head up
      tilt and lower body suction, and baroreceptor sensitivity by applying
      subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness
      was assessed from the relation between heart rate and oxygen uptake during a
      graded treadmill exercise test. Assessments were made before and after
      undertaking an exercise training programme (Canadian Air Force 5BX/XBX). RESULTS:
      After the training period, 12 of the 14 patients showed evidence of improved
      cardiorespiratory fitness. All 12 patients were symptomatically improved; they
      showed increases in plasma and blood volumes and in orthostatic tolerance, and
      decreases in baroreceptor sensitivity. Despite the improved orthostatic
      tolerance, values of blood pressure both while supine and initially following
      tilting were lower than before training. CONCLUSIONS: Exercise training has a
      role in the management of patients with syncope and poor orthostatic tolerance.
      It improves symptoms and increases orthostatic tolerance without increasing
      resting blood pressure.

PMID- 10065031
TI  - Measured versus predicted oxygen consumption in children with congenital heart
      disease.
AB  - OBJECTIVE: To compare measured and predicted oxygen consumption (VO2) in children
      with congenital heart disease. DESIGN: Retrospective study. SETTING: The cardiac
      catheterisation laboratory in a university hospital. PATIENTS: 125 children
      undergoing preoperative cardiac catheterisation. INTERVENTIONS: VO2 was measured
      using indirect calorimetry; the predicted values were calculated from regression
      equations published by Lindahl, Wessel et al, and Lundell et al. Stepwise linear
      regression and analysis of variance were used to evaluate the influence of age,
      sex, weight, height, cardiac malformation, and heart failure on the bias and
      precision of predicted VO2. An artificial neural network was trained and used to
      produce an estimate of VO2 employing the same variables. The various estimates
      for VO2 were evaluated by calculating their bias and precision values. RESULTS:
      Lindahl's equation produced the highest precision (+/- 42%) of the regression
      based estimates. The corresponding average bias of the predicted VO2 was 3%
      (range -66% to 43%). When VO2 was predicted according to regression equations by
      Wessel and Lundell, the bias and precision were 0% and +/- 44%, and -16% and +/-
      51%, respectively. The neural network predicted VO2 from variables included in
      the regression equations with a bias of 6% and precision +/- 29%; addition of
      further variables failed to improve this estimate. CONCLUSIONS: Both regression
      based and artificial intelligence based techniques were inaccurate for predicting
      preoperative VO2 in patients with congenital heart disease. Measurement of VO2 is
      necessary in the preoperative evaluation of these patients.

PMID- 10065032
TI  - Animal experimental implantation of an atrial septal defect occluder system.
AB  - OBJECTIVE: To establish the implantation technique for the atrial septal defect
      occluder system (ASDOS) device in an experimental animal model and to determine
      long term mechanical stability of the device and its in vivo properties in terms
      of biocompatibility and tissue reaction. MATERIALS AND METHODS: An atrial septal
      defect was created and the device implanted in 17 pigs (mean weight 30 kg). The
      implantation technique was refined and modified because of initial technical and
      anatomical complications during nine acute pilot studies. The technique proved to
      be feasible in eight subsequent survival studies. Four pigs were electively
      killed three months after implantation (group 1). The remaining four pigs were
      killed six months after implantation (group 2). RESULTS: Necropsy showed all
      devices were embedded in soft tissue three months after implantation. Microscopic
      examination of atrial septal tissue showed an acute granulomatous inflammatory
      reaction in group 1 and fibrosis in group 2. The intensity of the inflammatory
      reaction around the device was clearly milder in group 2, indicating a decline in
      the inflammatory response with time. Clinical and biochemical investigations
      indicated acceptable biocompatibility of the device. CONCLUSION: The implantation
      technique for the ASDOS device in a chronic pig model has been established.
      Biocompatibility of the device was acceptable.

PMID- 10065033
TI  - Images in cardiology. Vanishing tumour.

PMID- 10065034
TI  - Paul Wood Lecture. The master's legacy: the first Paul Wood Lecture.

PMID- 10065035
TI  - Reversal of severe pulmonary hypertension with beta blockade in a patient with
      end stage left ventricular failure.
AB  - A 52 year old man with severe chronic left ventricular failure (New York Heart
      Association class IV) was considered unsuitable for cardiac transplantation
      because of high and irreversible pulmonary vascular resistance (PVR). In an
      attempt to produce symptomatic improvement, metoprolol was cautiously introduced,
      initially at 6.25 mg twice daily. This was slowly increased to 50 mg twice daily
      over a two month period and continued thereafter. After four months of treatment
      the patient's symptoms had improved dramatically. His exercise tolerance had
      increased and diuretic requirements reduced to frusemide 160 mg/day only.
      Assessment of right heart pressures was repeated and, other than a drop in
      resting heart rate, there was little change in his pulmonary artery pressure or
      PVR. His right heart pressures were reassessed showing a pronounced reduction in
      pulmonary artery pressure and a significant reduction in PVR, which fell further
      with inhaled oxygen and sublingual nitrates. He was then accepted onto the active
      waiting list for cardiac transplantation. A possible mechanism of action was
      investigated by assessing responses to beta agonists during treatment. Not only
      was there pronounced improvement in PVR but it was also demonstrated that beta
      receptor subtype cross-regulation may have contributed to the mechanism of
      benefit.

PMID- 10065036
TI  - Carcinoid heart disease from ovarian primary presenting with acute pericarditis
      and biventricular failure.
AB  - A case is described of a 54 year old woman who had acute pericarditis with large
      exudative effusion accompanied by severe right and left ventricular failure. The
      patient was finally diagnosed with carcinoid heart disease from an ovarian
      carcinoid teratoma. She was treated with octreotide--a somatostatin analogue-
      followed by radical surgical resection of the neoplasm. At one year follow up
      only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid
      heart disease from an ovarian primary have been described in literature. Moreover
      clinically manifest acute, nonmetastatic pericarditis and left heart failure are
      not considered as possible presentations of carcinoid heart disease, whatever the
      origin. In a recent series a small pericardial effusion was considered an
      infrequent and unexpected echocardiographic finding in carcinoid heart patients.
      One case of "carcinoid pericarditis" has previously been described as a
      consequence of pericardial metastasis. Left sided heart involvement is usually
      caused by bronchial carcinoids or patency of foramen ovale; both were excluded in
      the case presented.

PMID- 10065037
TI  - Junctional ectopic tachycardia evolving into complete heart block.
AB  - Transition from congenital junctional ectopic tachycardia to complete AV block
      was observed in an 8 month old girl, over a 36 hour period, during initial
      hospital admission. Two years later she had evidence of a rapidly increasing left
      ventricular end diastolic diameter, associated with lowest heart rates during
      sleep of < 30 beats/min. A transvenous permanent pacemaker was therefore
      implanted. This finding supports the idea that a pathological process in the area
      of the AV junction, initially presenting as junctional ectopic tachycardia may
      later extend to sudden complete atrioventricular block.

PMID- 10065038
TI  - Anomalous origin of the left coronary artery from the pulmonary artery: natural
      history and normal pregnancies.
AB  - Two female patients are described with anomalous origin of the left coronary
      artery arising from the pulmonary artery who sustained an anterolateral
      myocardial infarction in infancy. Neither patient received surgical treatment
      although both have lived to middle age with minimal cardiovascular problems and
      have had uncomplicated pregnancies. Good exercise tolerance and long term
      survival may be possible even without surgery for patients with this anomaly.

PMID- 10065039
TI  - Hypertrabeculated left ventricle in mitochondriopathy.

PMID- 10065040
TI  - Arterial remodelling and eccentricity of plaque.

PMID- 10065041
TI  - Bifid T waves induced by isoprenaline in a patient with Brugada syndrome.

PMID- 10065042
TI  - Nocturnal desaturation in patients with stable heart failure.

PMID- 10065043
TI  - Questioning U.S. residency training.

PMID- 10065044
TI  - Ambulatory surgery rotation for pediatrics residents.

PMID- 10065045
TI  - New teaching tool for biostatistics.

PMID- 10065046
TI  - Residents' attitudes toward patient feedback.

PMID- 10065047
TI  - Little-heralded advantages of problem-based learning.

PMID- 10065048
TI  - Medical schools and state legislatures as partners in a changing policy world.

PMID- 10065049
TI  - Time to rethink accreditation criteria for programs that train health
      professionals.

PMID- 10065050
TI  - Scientists, senators, and "software": the keys to unlocking our future.
AB  - Scientists, educators, and researchers in the nation's medical schools, teaching
      hospitals, and research universities have responsibilities for ensuring a bright
      future for medical research. First, they must define science and communicate its
      wonder to their students, be their role models and mentors, and nurture and
      encourage the best and brightest to enter careers in medical research, since they
      are a precious resource for solving the many challenging and complex research
      problems that await them and which can bring great benefits to society. Second,
      they must learn to participate even more effectively and actively in the ongoing
      partnerships between the federal government, private enterprise, and the medical
      school and in the processes that lead to appropriations for the funding necessary
      to support the research enterprise. And finally, they need to recognize the
      importance of the increasingly interdisciplinary nature of medical research by
      urging support for the physical and social sciences, mathematics, and
      engineering.

PMID- 10065051
TI  - Honoring the "E" in GME.
AB  - Medical educators should realize that the public's complaints about doctors--that
      they don't care enough about their patients, don't know enough to practice the
      best medicine, and don't do enough to maintain the public's trust--are
      exaggerations of the truth but highlight areas demanding improvement in the
      educational component of graduate medical education (GME). In addition to
      continuing to prepare residents for the demanding technical challenges they will
      face as physicians, those involved in GME need to (1) enrich significantly the
      educational content of residency programs; (2) promote the coordination,
      strengthening, and potential consolidation of the institutional responsibility
      for these programs; (3) reorder programs' priorities to make room for the added
      educational content, which means limiting service requirements to those necessary
      to meet prospectively defined educational goals; and (4) recognize the power of
      the hidden curriculum in communicating professional values, and thus modify
      significantly the way residents are treated. The author explains these
      recommendations in detail and notes a variety of ways that the Association of
      American Medical Colleges intends to help educators make these needed changes. He
      concludes by stating that a "time bomb" is ticking: many sectors of the public
      and many patients are becoming impatient with doctors. "Listening hard to their
      complaints and finding appropriate remedies is a must if we are going to ...
      answer our critics ... and continue to provide America with the world's best
      doctors."

PMID- 10065052
TI  - The "Balanced Scorecard": development and implementation in an academic clinical
      department.
AB  - If quality medical education is to survive in the increasingly competitive
      marketplace, medical schools need to adopt new tools that measure the value of
      all initiatives, both financial and non-financial, so that they can make informed
      decisions about their missions and future direction. The authors describe a tool
      of this kind called the Balanced Scorecard (originally created for traditional
      businesses), outline the version of it that they developed for the Department of
      Anesthesiology at Yale University School of Medicine, and discuss the first year
      of implementation (which began in 1997). The Balanced Scorecard is a set of
      measures designed to examine an organization's performance from the following
      four perspectives and to answer the key question suggested by each perspective:
      (1) The learning and growth perspective: Can we continue to improve and create
      value? (2) The internal business perspective: What must we excel at? (3) The
      customer perspective: How do our customers see us? (4) The financial perspective:
      How do we look to our shareholders? The first year of implementation of this
      approach at the Department of Anesthesiology involved creating measures of the
      four perspectives, determining whether data could be found for each measure and
      whether the data were in usable forms, and educating and involving the faculty in
      the process. The authors discuss the pros and cons of the Balanced Scorecard
      approach that they observed during the first year, and conclude with a list of
      seven lessons learned (e.g., start with measures that already exist). Overall,
      they are convinced that the Balanced Scorecard can be of great value to a
      department, even if the full implementation takes several years to complete.

PMID- 10065053
TI  - Implementation of a four-year multimedia computer curriculum in cardiology at six
      medical schools.
AB  - The pressures of a changing health care system are making inroads on the
      commitment and effort that both basic science and clinical faculty can give to
      medical education. A tool that has the potential to compensate for decreased
      faculty time and thereby to improve medical education is multimedia computer
      instruction that is applicable at all levels of medical education, developed
      according to instructional design principles, and supported by evidence of
      effectiveness. The authors describe the experiences of six medical schools in
      implementing a comprehensive computer-based four-year curriculum in bedside
      cardiology developed by a consortium of university cardiologists and educational
      professionals. The curriculum consisted of ten interactive, patient-centered,
      case-based modules focused on the history, physical examination, laboratory data,
      diagnosis, and treatment. While an optimal implementation plan was recommended,
      each institution determined its own strategy. Major goals of the project, which
      took place from July 1996 to June 1997, were to identify and solve problems of
      implementation and to assess learners' and instructors' acceptance of the system
      and their views of its value. A total of 1,586 students used individual modules
      of the curriculum 6,131 times. Over 80% of students rated all aspects of the
      system highly, especially its clarity and educational value compared with
      traditional lectures. The authors discuss the aspects of the curriculum that
      worked, problems that occurred (such as difficulties in scheduling use of the
      modules in the third year), barriers to change and ways to overcome them (such as
      the type of team needed to win acceptance for and oversee implementation of this
      type of curriculum), and the need in succeeding years to formally assess the
      educational effectiveness of this and similar kinds of computer-based curricula.

PMID- 10065054
TI  - Contemporary issues in medicine--medical informatics and population health:
      report II of the Medical School Objectives Project.
AB  - The Association of American Medical Colleges established the Medical School
      Objectives Project (MSOP) to set forth program-level learning objectives that
      medical school deans and faculties can use as guides in reviewing their medical
      student education programs (initial phase), and to suggest strategies that they
      might employ in implementing agreed-upon changes in those programs
      (implementation phase). The publication of MSOP Report I in 1998 concluded the
      initial phase of the project by presenting 30 program-level learning objectives
      that represent a consensus within the medical education community on the
      knowledge, skills, and attitudes that students should possess before graduation
      from medical school. Report II, published here, is the work of two expert panels
      that focus on the two interrelated topics of medical informatics and population
      health for which Report I developed learning objectives. The Medical Informatics
      Panel identified five roles played by physicians--lifelong learner, clinician,
      educator-communicator, researcher, and manager--in which medical informatics
      plays a vital part, and defined one or more informatics learning objectives
      important for each role (e.g., the successful medical school graduate, in his or
      her role as a clinician, should be able to retrieve patient-specific information
      from a clinical information system). The panel then identified ways that schools
      might implement educational programs to address the various informatics learning
      objectives and to eventually embed informatics experiences throughout the
      curriculum rather than relying on an informatics course to achieve some or all of
      the objectives. The Population Health Perspective Panel developed a consensus
      definition of "population health perspective" (PHP); chose four types of
      populations to discuss (e.g., the geographic community); reviewed pressures for
      and against the implementation of a PHP in the curriculum (e.g., the cross
      disciplinary nature of the topic is a barrier); named the fields that encompass
      training in a PHP (e.g., public health); listed several educational objectives,
      three principles to govern the design of educational activities, and a number of
      recommendations; and closed with a list of the knowledge, skills, and attitudes
      that should be instilled by a successful PHP curriculum.

PMID- 10065055
TI  - Content in context: medical education and society's needs.
AB  - Many reports have emphasized the need to reform medical education to bring it
      into harmony with society's needs and expectations. Although much effort has been
      expended over several decades, many believe that reform initiatives have not
      successfully modified physicians' behaviors and attitudes. More recently, two
      major projects--Educating Future Physicians for Ontario and the Medical School
      Objectives Project--have identified physician roles and attributes necessary to
      meet societal needs. These efforts have provided a substantial framework upon
      which the content and conduct of a more relevant kind of medical education can be
      built. In order to implement real change, however, medical schools must (1) take
      the long view, making reform part of the entire continuum of medical education;
      (2) ensure that faculty physicians teach by example; (3) change student
      assessments to reflect new educational objectives; and (4) reallocate resources
      to support a changed curriculum.

PMID- 10065056
TI  - Multimedia electronic medical record systems.
AB  - A wide range of imaging technologies are becoming increasingly important to the
      practice of medicine. In addition, many medical specialties are highly visual,
      independent of their use of new imaging modalities. Because today's medical
      record contains text, images, and physiologic signals, it is inherently
      multimedia in nature. However, most electronic medical record systems handle only
      the textual portion of the patient record, resulting in a fragmentation of the
      database that physicians need to make timely, effective clinical decisions.
      Advances in database-, storage-, data-compression, and networking technologies
      will facilitate the development of multimedia electronic medical record systems
      for the 21st century. These systems will become widely used over the next decade,
      and in addition to enhancing patient care, will also present new opportunities
      for using clinical imaging data for biomedical research and education.

PMID- 10065057
TI  - Medical curriculum reform in North America, 1765 to the present: a cognitive
      science perspective.
AB  - Since 1765, five major curricular reform movements have catalyzed significant
      changes in North American medical education. This article describes each reform
      movement in terms of its underlying educational practices and principles,
      inherent instructional problems, and the innovations that were carried forward.
      When considering the motivating factors underlying these reform movements, a
      unifying theme gradually emerges: increasing interest in, attention to, and
      understanding of the knowledge-base structures and cognitive processes that
      characterize and distinguish medical experts and novices. Concurrent with this
      emerging theme is a growing realization that medical educators must call upon and
      utilize the literature, research methods, and theoretical perspectives of
      cognitive science if future curricular reform efforts are to move forward
      efficiently and effectively. The authors hope that the discussion and perspective
      offered herein will broaden, stimulate, and challenge educators as they strive to
      create the reform movements that will define 21st-century medical education.

PMID- 10065058
TI  - Do we all mean the same thing by "problem-based learning"? A review of the
      concepts and a formulation of the ground rules.
AB  - Problem-based learning (PBL) has emerged as a useful tool of epistemological
      reform in higher education, particularly in medical schools. Indeed, PBL has
      spent most of its career inducing revolutionary undergraduate medical reform.
      Nevertheless, obtaining informed agreement on the characteristics of the PBL
      "genus" is a challenge when the label is vulnerable to being borrowed for
      prestige or subversion. Many "PBL" single-subject courses within traditional
      curricula do not use PBL at all. Such semantic uncertainty compromises the
      evidence-base on the added value of problem-based versus traditional approaches
      and the main messages for good practice. This literature review explores what is
      meant by the term PBL by aiming to answer the following questions: What
      difficulties are inherent in the "problem-based" tag? What does the term "problem
      based curriculum" imply? How has PBL been characterized and validated by focusing
      on its purpose? How else has PBL been characterized? How does PBL relate to
      problem solving? How does PBL relate to epistemological reform? In conclusion,
      what ground rules can be formulated for PBL? Despite much conceptual fog
      lingering over the PBL literature, useful ground rules can be formulated.

PMID- 10065059
TI  - What learners and teachers value most in ambulatory educational encounters: a
      prospective, qualitative study.
AB  - PURPOSE: To determine what learners and teachers value most in ambulatory
      learning encounters and whether the choices of the two groups are in concordance.
      METHOD: In 1996, the authors surveyed learners and teachers at a walk-in clinic
      immediately after each of 103 consecutive learning encounters. The participants
      answered two open-ended questions: (1) What was the one most valuable aspect of
      this learning encounter? and (2) List one thing that would make it better. Using
      qualitative analysis methods, two raters categorized the responses; their
      agreement was substantial (kappa = .75). RESULTS: Half the responses fit five
      categories: diagnosis (15%), general management (14%), physical examination
      skills (9%), patient selection (6%), and time issues (6%). The participants most
      valued general exposure to diagnosis (29%) and general management issues (29%).
      Regarding their suggestions for improving the encounters, 33% cited structural
      issues (often "more time"), while 43% had no suggestions ("nothing" or "fine as
      is"). Substantial concordance existed between the rankings by category of the
      teachers' and learners' comments, but (1) learners were more likely to rate the
      educational value of the encounter excellent or very good (64% vs 47%, p < .01);
      (2) teachers were more likely than medical students (but not interns) to place
      the most educational value on the physical examination (30% vs 4%, p = .001); and
      (3) agreement on what was most valuable in any individual encounter was poor
      (kappa = .03). CONCLUSIONS: In evaluating ambulatory educational encounters,
      learners and teachers placed highest value on general exposure to diagnosis and
      disease management; while the most commonly recommended changes related to
      structural issues, particularly inadequate time. While learners and teachers
      agreed in general on the relative ranking of teaching activities, they often
      found different things to be educationally salient in a particular encounter.

PMID- 10065060
TI  - Effect of the framing of questionnaire items regarding satisfaction with training
      on residents' responses.
AB  - PURPOSE: To determine whether framing questions positively or negatively
      influences residents' apparent satisfaction with their training. METHOD: In 1993
      94, 276 residents at five Canadian internal medicine residency programs responded
      to 53 Likert-scale items designed to determine sources of the residents'
      satisfaction and stress. Two versions of the questionnaire were randomly
      distributed: one in which half the items were stated positively and the other
      half negatively, the other version in which the items were stated in the opposite
      way. RESULTS: The residents scored 43 of the 53 items higher when stated
      positively and scored ten higher when stated negatively (p < .0001). When
      analyzed using an analysis-of-variance model, the effect of positive versus
      negative framing was highly significant (F = 129.81, p < .0001). While the
      interaction between item and framing was also significant, the effect was much
      less strong (F = 5.56, p < .0001). On a scale where 1 represented the lowest
      possible level of satisfaction and 7 the highest, the mean score of the
      positively stated items was 4.1 and that of the negatively stated items, 3.8, an
      effect of 0.3. CONCLUSIONS: These results suggest a significant "response
      acquiescence bias." To minimize this bias, questionnaires assessing attitudes
      toward educational programs should include a mix of positively and negatively
      stated items.

PMID- 10065061
TI  - An intervention to increase patients' trust in their physicians. Stanford Trust
      Study Physician Group.
AB  - PURPOSE: To investigate the effect of a one-day workshop in which physicians were
      taught trust-building behaviors on their patients' levels of trust and on
      outcomes of care. METHOD: In 1994, the study recruited 20 community-based family
      physicians and enrolled 412 consecutive adult patients from those physicians'
      practices. Ten of the physicians (the intervention group) were randomly assigned
      to receive a one-day training course in building and maintaining patients' trust.
      Outcomes were patients' trust in their physicians, patients' and physicians'
      satisfaction with the office visit, continuity in the patient-physician
      relationship, patients' adherence to their treatment plans, and the numbers of
      diagnostic tests and referrals. RESULTS: Physicians and patients in the
      intervention and control groups were similar in demographic and other data. There
      was no significant difference in any outcome. Although their overall ratings were
      not statistically significantly different, the patients of physicians in the
      intervention group reported more positive physician behaviors than did the
      patients of physicians in the control group. CONCLUSIONS: The trust-building
      workshop had no measurable effect on patients' trust or on outcomes hypothesized
      to be related to trust.

PMID- 10065062
TI  - Teaching a screening musculoskeletal examination: a randomized, controlled trial
      of different instructional methods.
AB  - PURPOSE: To develop and test a program to teach a rapid screening musculoskeletal
      examination. METHOD: In 1995, 191 medical and physician assistant students were
      randomized to four intervention groups: written materials only (n = 47), written
      materials and videotape (n = 46), written materials and small-group sessions
      facilitated by fourth-year medical students (n = 55), and all three methods (n =
      43). Assessments, in the form of a written test and standardized patient
      examinations, were conducted before the interventions (n = 40 randomly selected
      students), seven to ten days and again three months after the interventions (n =
      all 191 students), and 16 months after the interventions (n = 103 students).
      RESULTS: While the four intervention groups' written test scores were
      approximately equal, their scores on the standardized patient examination
      differed significantly. The students taught in small groups demonstrated
      significantly superior examination skills compared with the students taught with
      written material or videotape at seven to ten days and retained this relative
      superiority after three and 16 months (p < .0001). CONCLUSION: Small-group
      instruction with hands-on supervised practice is superior to more passive
      instructional methods for teaching musculoskeletal examination skills and can be
      successfully delivered by trained senior medical student facilitators with
      minimal direct expenditure of faculty time.

PMID- 10065063
TI  - Evaluation of clinical performances of emergency medicine residents using
      standardized patients.

PMID- 10065064
TI  - Evaluation of medical students' performances using the anesthesia simulator.

PMID- 10065066
TI  - Few family physicians go it alone.

PMID- 10065065
TI  - Winter can be fun until the injuries start.

PMID- 10065067
TI  - Defining futility.

PMID- 10065068
TI  - Temporary henna tattoo with permanent scarification.

PMID- 10065069
TI  - Chiropractors here to stay.

PMID- 10065070
TI  - Give it and they will spend.

PMID- 10065071
TI  - Norwood reconstruction.

PMID- 10065072
TI  - Signed consent for publication.

PMID- 10065073
TI  - Dictated versus database-generated discharge summaries: a randomized clinical
      trial.
AB  - BACKGROUND: Hospital discharge summaries communicate information necessary for
      continuing patient care. They are most commonly generated by voice dictation and
      are often of poor quality. The objective of this study was to compare discharge
      summaries created by voice dictation with those generated from a clinical
      database. METHODS: A randomized clinical trial was performed in which discharge
      summaries for patients discharged from a general internal medicine service at a
      tertiary care teaching hospital in Ottawa were created by voice dictation (151
      patients) or from a database (142 patients). Patients had been admitted between
      September 1996 and June 1997. The trial was preceded by a baseline cohort study
      in which all summaries were created by dictation. For the database group,
      information on forms completed by housestaff was entered into a database and
      collated into a discharge summary. For the dictation group, housestaff dictated
      narrative letters. The proportion of patients for whom a summary was generated
      within 4 weeks of discharge was recorded. Physicians receiving the summary rated
      its quality, completeness, organization and timeliness on a 100-mm visual
      analogue scale. Housestaff preference was also determined. RESULTS: Patients in
      the database group and the dictation group were similar. A summary was much more
      likely to be generated within 4 weeks of discharge for patients in the database
      group than for those in the dictation group (113 [79.6%] v. 86 [57.0%]; p <
      0.001). Summary quality was similar (mean rating 72.7 [standard deviation (SD)
      19.3] v. 74.9 [SD 16.6]), as were assessments of completeness (73.4 [SD 19.8] v.
      78.2 [SD 14.9]), organization (77.4 [SD 16.3] v. 79.3 [SD 17.2]) and timeliness
      (70.3 [SD 21.9] v. 66.2 [SD 25.6]). Many information items of interest were more
      likely to be included in the database-generated summaries. The database system
      created summaries faster and was preferred by housestaff. Dictated summaries in
      the baseline and randomized studies were similar, which indicated that the
      control group was not substantially different from the baseline cohort.
      INTERPRETATION: The database system significantly increased the likelihood that a
      discharge summary was created. Housestaff preferred the database system for
      summary generation. Physicians thought that the quality of summaries generated by
      the 2 methods was similar. The use of computer databases to create hospital
      discharge summaries is promising and merits further study and refinement.

PMID- 10065074
TI  - Prevalence and treatment of pain in older adults in nursing homes and other long
      term care institutions: a systematic review.
AB  - BACKGROUND: The high prevalence of pain in older adults and its impact in this
      age group make it a public health issue, yet few studies of pain relief focus on
      older adults. Residents of long-term care facilities have more cognitive
      impairment than their community-living counterparts and may have difficulty
      reporting the presence and severity of pain. This systematic literature review
      was conducted to determine the prevalence of pain, and the type and effectiveness
      of interventions that have been used to treat pain in residents of nursing homes.
      METHODS: Studies were identified by searching MEDLINE (from January 1966 to May
      1997), HEALTH (from January 1975 to May 1997), CINAHL (from January 1982 to April
      1997), AGELINE (from January 1978 to April 1997) and the Cochrane Library (1997,
      issue 1) and by performing a manual search of textbooks and reference lists.
      Studies of any methodological design were included if they estimated the
      prevalence of pain in nursing homes or other long-term care institutions or
      evaluated interventions for the treatment of pain in residents. Of the 14
      eligible studies, 12 were noncomparative studies, 1 was a comparison study with
      nonrandomized contemporaneous controls, and 1 was a randomized controlled trial.
      Information on several factors was extracted from each study, including study
      design, number of patients and facilities, main outcomes measured, methods used
      to identify and detect pain, prevalence and types of pain, and interventions used
      to treat pain. The strength of the evidence provided by each study was also
      assessed. RESULTS: In the 6 studies with data from self-reporting or chart
      reviews, the prevalence of pain ranged from 49% to 83%. In the 5 studies with
      data on analgesic use only, the prevalence of pain ranged from 27% to 44%. Only 3
      studies, with just 30 patients in total, evaluated an intervention for the
      treatment of pain. INTERPRETATION: Despite the high prevalence of pain in
      residents of nursing homes, there is a lack of studies evaluating interventions
      to relieve their pain. The authors make recommendations for future studies in
      this area.

PMID- 10065075
TI  - Screening Mammography Program of British Columbia: pattern of use and health care
      system costs.
AB  - BACKGROUND: The use of mammography for screening asymptomatic women has increased
      dramatically in the past decade. This report describes the changes that have
      occurred in the use of bilateral mammography in British Columbia since the
      provincial breast cancer screening program began in 1988. METHODS: Using province
      wide databases from both the breast cancer screening program and the provincial
      health insurance plan in BC, the authors determined the number and costs of
      bilateral mammography services for women aged 40 years or older between Apr. 1,
      1986, and Mar. 31, 1997. Unilateral mammography was excluded because it is used
      for investigating symptomatic disease and screening abnormalities, and for follow
      up of women who have undergone mastectomy for cancer. RESULTS: As the provincial
      breast cancer screening program expanded from 1 site in 1988 to 23 in 1997, it
      provided an increasing proportion of the bilateral mammographic examinations
      carried out each year in BC. In fiscal year 1996/97, 65% of bilateral
      mammographic examinations were performed through the screening program. The cost
      per examination within the screening program dropped as volume increased. Thirty
      percent more bilateral mammography examinations were done in 1996/97 than in
      1991/92, but health care system expenditures for these services increased by only
      4% during the same period. In calendar year 1996, 21% of new breast cancers were
      diagnosed as a result of a screening program visit. INTERPRETATION: Substantial
      increases in health care expenditures have been avoided by shifting bilateral
      mammography services to the provincial screening program, which has a lower cost
      per screening visit.

PMID- 10065076
TI  - "Conventional" dictated versus database-generated discharge summaries:
      timeliness, quality and completeness.

PMID- 10065077
TI  - Medical students' attitudes toward women: are medical schools microcosms of
      society?

PMID- 10065078
TI  - Adverse reporting on adverse reactions.

PMID- 10065079
TI  - Discussing complementary therapies: there's more than efficacy to consider.

PMID- 10065080
TI  - Penetrating sledding injuries to the lower torso--2 case reports.
AB  - Sledding accidents are frequent and vary in severity. Penetrating sledding
      injuries are uncommon but may be devastating. Snow-racers--sleds with both
      steering and braking devices--may be associated with an increased rate of injury.
      The authors present 2 cases of lower-torso penetrating trauma associated with the
      use of snow-racers. Both cases involved penetration--of the perineum in one case
      and the inguinal area in the other--by wooden sticks. Both patients recovered
      fully after prompt surgical intervention. The authors suggest that the absence of
      a protective panel at the front of the snow-racer may result in the sledder's
      lower torso being more exposed to objects encountered while sledding. The
      injuries reported raise concerns about the safety of modern sleds and the
      possibility that design changes are needed.

PMID- 10065081
TI  - Do students' attitudes toward women change during medical school?
AB  - BACKGROUND: Medical school has historically reinforced traditional views of
      women. This cohort study follows implementation of a revitalized curriculum and
      examines students' attitudes toward women on entry into an Ontario medical
      school, and 3 years later. METHODS: Of the 75 students entering first year at
      Queen's University medical school 70 completed the initial survey in September
      1994 and 54 were resurveyed in May 1997. First-year students at 2 other Ontario
      medical schools were also surveyed in 1994, and these 166 respondents formed a
      comparison group. Changes in responses to statements about sex-role stereotypes,
      willingness to control decision-making of female patients, and conceptualization
      of women as "other" or "abnormal" because they are women were examined. Responses
      from the comparison group were used to indicate whether the Queen's group was
      representative. RESULTS: Attitudinal differences between the primary group and
      the comparison group were not significant. After 3 years of medical education
      students were somewhat less accepting of sex-role stereotypes and less
      controlling in the doctor-patient encounter. They continued, however, to equate
      adults with men and to see women as "not adult" or "other." Female students began
      and remained somewhat more open-minded in all areas studied. INTERPRETATION: A
      predicted trend toward conservatism was not seen as students became older, more
      aware and closer to completion of medical training, although they continued to
      equate adults with male and to see women as "other." Findings may validate new
      curricular approaches and increased attention to gender issues in the academic
      environment.

PMID- 10065083
TI  - The wintertime blues.

PMID- 10065082
TI  - Prostate cancer: 10. Palliative care.

PMID- 10065084
TI  - The Internet comes to Africa.

PMID- 10065085
TI  - Independent review adds to controversy at Sick Kids.

PMID- 10065086
TI  - Canada's "disasters-R-us" medical platoon a hit in Honduras.
AB  - The Canadian Forces Disaster Assistance Response Team did not take long to adapt
      to the medical needs of 90,000 survivors of Hurricane Mitch last November.

PMID- 10065087
TI  - After Swissair 111, the helpers needed help.

PMID- 10065088
TI  - [Endocrine disrupting chemicals and carcinogenicity].
AB  - Endocrine disrupting chemicals (EDC) seem to be different from classic
      environmental toxicants in several points: 1) EDC operates during critical period
      (s) in the early stage of life characterized by rapid cell differentiation and
      organogenesis, leaving irreversible disruption thereof. 2) EDC may not
      demonstrate any clear threshold in exerting its "toxicological" effects and 3)
      EDCs may act synergistically or additively. Except for few cases such as
      diethylstilbestrol causing cancer in female offspring, a clear cause effect
      relationship between cancers in humans and EDC is still hard to demonstrate.
      Thanks to continual epidemiological endeavors, a few reports suggests such
      relationship between prostate cancer and herbicides. Because of its frequent
      association in incidence with inborn abnormalities of male reproductive organs
      such as undescended testis, hypospadias and degenerated quality of sperm,
      testicular cancer is suspected to have common or related pathogenesis with them.
      A hypothesis advanced by Carlsen et al was introduced.

PMID- 10065089
TI  - Basic research supported developments of chemotherapy in nonresectable isolated
      colorectal liver metastases to a protocol of hepatic artery infusion using
      mitoxantrone, 5-FU + folinic acid and mitomycin C.
AB  - OBJECTIVE: Since the developments in systemic chemotherapy of metastasized
      colorectal cancer have not resulted in substantial gains in survival times, we
      wished to improve the course of isolated nonresectable colorectal liver
      metastases (CPLM) by hepatic arterial infusion treatment. BACKGROUND: Patients
      (pts) with CRLM have a worse fate than those pts whose liver metastases could be
      resected. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases does not
      improve survival to a relevant level (median survival time (med. surv.) after 5
      Fluorouracil + Folinic Acid (5-FU + FA) i.v.: 6.4-14.3 months (m)). Hepatic
      artery infusion (HAI) with 5-Fluorode-oxyuridine (5-FUDR) has been demonstrated
      in a metaanalysis of randomized trials to be superior to i.v.
      treatment/palliative care (med. surv.: 15 vs. 10 m). The benefit of HAI with 5
      FUDR, although recommended as treatment for CRLM, is severely compromised by the
      5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis
      (SC)/liver scirrhosis. We have stepwise developed a protocol for HAI of CRLM,
      which is superior to HAI with 5-FUDR, and, most evidently, to systemic
      chemotherapy. PATIENTS/METHODS: Between 1982-1997, 222 CR (L) M patients were
      treated within subsequent protocols (Table). In protocol A, 68 CRLM pts received
      HAI with 5-FUDR (A1: nonrandomized pts; A2: randomized pts). In protocol B
      (randomized pts.), 46 pts received 5-FUDR i.a. (via HAI) + i.v. In protocol C,
      systemic chemotherapy with 5-FU + FA was conducted in 34 pts with metastasized
      colorectal cancers, including CRLM. In protocol D 5-FU + FA was delivered via HAI
      in 25 pts with CRLM. In protocol E, based on in vitro phase II studies and the
      results of protocol D, Mitoxantrone and Mitomycin C were added to 5-FU + FA
      (MFFM). Fifty (50) CRLM pts received HAI with MFFM. RESULTS: The response rates,
      med. surv. times, systemic toxicity and SC rates are shown in the table. HAI with
      MFFM produced objective responses in 66%, the med. surv. was 27.4 m, and no SC
      occurred. The ports surgically placed for HAI, e.g., in protocols D and E,
      functioned in 90%, 82%, and 76% 6, 9, and 11 m after start of the HAI. Quality of
      life in protocol E was high. Nine pts from protocols D + E with either partial
      (PR, 7 pts) or complete (CR, 2 pts) remissions received a secondary liver
      resection without hospital mortality, and 7/9 pts are living 2-58 m after liver
      resection, 2/9 pts died 11 and 22 m after resection. [table: see text]
      SUMMARY/CONCLUSIONS: Our learning curve to achieve optimal treatment of CRLM
      resulted in a protocol using HAI with MFFM. The results of this protocol (E)
      including the high remission rate, long median survival time, good port function,
      high quality of life, and, most interestingly, the possibility to downstage and
      resect primarily nonresectable metastases, seem to be superior to HAI with 5-FUDR
      of 5-FU + FA and to systemic chemotherapy with 5-FU + FA. This hypothesis is
      currently examined in a phase III study (HAI with MFFM vs. 5-FU + FA i.v.).

PMID- 10065090
TI  - [Gastrointestinal cancer and oral anticancer agents].
AB  - 5-FU has been very valuable as an anticancer agent since it was first developed
      by Heidelberger in 1957. For over 40 years it has been used either by itself or
      in combination therapy for the treatment of patients with all types of malignant
      tumors. To date, no better anticancer agent has been developed for the treatment
      of patients with gastrointestinal tract cancer. During administration,
      consideration for a combined regimen from the standpoints of dose intensity,
      schedule dependency, and biochemical modulation can improve the antitumor
      effectiveness of 5-FU. It has been found to be most effective if administered by
      long term (if possible, 4 weeks or more) intravenous or intraarterial continuous
      drip infusion. However, there are also negative aspects. The dose-limiting
      toxicity with drip infusions brings about gastrointestinal disorders such as
      stomatitis and diarrhea. Furthermore, the possibility of trouble and difficulty
      in managing a catheter kept in the body over long periods not only greatly
      reduces the patient's QOL, it is also very inconvenient for the patient and
      increases medical costs. Since the development of oral FT by Kimura, however,
      many 5-FU prodrugs and masked compounds have been developed in Japan. The aim has
      been to see how far the concentration of 5-FU in the blood and cancer tissues
      could be raised. UFT, 5'-DFUR, and HCFU have been developed as derivatives of 5
      FU, and these are widely used clinically either alone or in combination therapy.
      With the aim of further improving antitumor effectiveness and reducing side
      effects, these compounds have been improved from the viewpoints of
      pharmacodynamics and pharmalokinetics, based on biochemical modulation, to create
      S-1 and Capecitabine. Although these are still currently undergoing clinical
      trials, sufficient results have already been obtained. Cisplatin and CPT-11 are
      effective for use in the gastrointestinal tract, and much work is going on now to
      allow these to be taken orally. Future prospects indeed look bright.

PMID- 10065091
TI  - [Oral antitumor drugs for hematological malignancies].
AB  - The oral antitumor drugs against hematological malignancies are summarized.
      Sobuzoxane, a topoisomerase II inhibitor, is useful for the treatment of
      lymphoma, especially adult T cell leukemia/lymphoma. Sobuzoxane has an effect to
      protect against doxorubicin cardiotoxicity. Cytarabine ocfosfate, a derivative of
      cytosine arabinoside, is a useful agent against acute leukemia and MDS,
      especially RAEB, RAEB in T, CMMoL. The JALSG AML 92 study for APL with all-trans
      retinoic acid resulted in a 89% CR rate in 196 and 64% 4-year DFS in CR cases.
      Hydroxycarbamide is can control the WBC in CML. This agent is also effective for
      other myeloproliferative disorders, such as acute leukemia and MDS. Oral
      administration of 50 mg etoposide daily showed a good outcome in old patients
      with malignant lymphoma. For old patients and those with refractory hematological
      malignancies, oral administration of these agents can offer a new form of
      palliative therapy to allow them to remain at home while maintaining a high
      quality of life.

PMID- 10065092
TI  - [Recent development of oral anti-cancer drugs for breast cancer].
AB  - Oral anti-cancer drugs play an important role in the treatment of breast cancer.
      Because these hormonal agents are related to mammary carcinogenesis and tumor
      growth, they are used not only for therapy but also to prevent the onset of the
      disease. Tamoxifen, toremifene, fadrozole and other aromatase inhibitors,
      goserelin, leuprolin and MPA are used widely in Japan as hormonal anti-cancer
      drugs. In addition oral anti-cancer chemotherapeutic agents, such as
      cyclophosphamide, 5-FU, 5'-DFUR, FT and UFT are used for breast cancer. The
      combination of these hormonal and chemotherapeutic agents produces good clinical
      results in curing the disease. Oral drugs are superior to injected drugs with
      regard to the QOL of patients.

PMID- 10065093
TI  - [Progress in oral anti-cancer drug therapy for urological cancer].
AB  - We describe the progress in oral anti-cancer drug therapy for urological cancer.
      Pure antiandrogen (e.g., flutamide) is widely used as a means of maximal androgen
      blockade (MAB) in the treatment of prostate cancer. However, all series reported
      in the past several years did not show positive effects on prolongation of the
      patient's survival. Evaluations by meta-analysis are in progress. As the
      mechanism of antiandrogen withdrawal syndrome has been recognized, it was widely
      accepted that antiandrogen should be discontinued when disease progression or PSA
      elevation becomes evident. Estramustine was recently clarified as an effective
      therapeutic agent in the treatment of hormone refractory prostate cancer in
      combination with oral etoposide. Oral etoposide therapy has been tried as a
      maintenance or a palliative chemotherapy for non-curative or high-risk germ cell
      tumor. UFT (a compound of tegafur and uracil) is said to be effective for bladder
      cancer. It has been also suggested that UFT was partly effective as a means of
      first-line endocrine chemotherapy for advanced prostate cancer and was a
      promising agent in the treatment of advanced renal cell carcinoma in combination
      with Interferon-alpha. Usually the age of the patient with urological malignancy,
      excluding testicular cancer, is high and complicated. For such patients, an
      aggressive intravenous chemotherapy can not always be used. Therefore, a less
      aggressive, less toxic chemotherapy with oral drug is often planned to maintain
      QOL.

PMID- 10065094
TI  - [Preliminary evaluation of adjuvant chemotherapy against stage Ib or II gastric
      cancer].
AB  - The prognostic influence of post-operative adjuvant chemotherapy on stage I b or
      II gastric cancer was studied retrospectively. The immunohistochemical
      expressions of p53 protein and thymidine phosphorylase (TP) were also examined;
      the relations between these protein expressions and clinicopathological features
      along with the effect of adjuvant chemotherapy were also investigated. The 5-year
      survival rate of the patients who received adjuvant chemotherapy was 95.5%, which
      was better than that (89.8%) of those who did not, although the difference did
      not reach significance (p = 0.09). The venous invasion of tumor was slight
      frequently observed in p53 or TP positive cases than negative cases, respectively
      (p < 0.1), but no significant associations were found between the t-, n- or ly
      factor, and p53 or TP expression. Moreover p53 and TP expression had no
      significant influence on post-operative survival. But, among the patients with
      p53- or TP-positive tumor, adjuvant chemotherapy conferred survival benefits,
      although the difference did not reach significance. The 5-year survival rate was
      100% with adjuvant chemotherapy, 84.3% without chemotherapy in p53-positive
      patients (p = 0.137), 97.0% with adjuvant chemotherapy, and 90.8% without
      chemotherapy in TP-positive tumors (p = 0.326).

PMID- 10065095
TI  - [The expression of thymidylate synthase and thymidine phosphorylase in the early
      stage of gastric cancer].
AB  - The immunohistochemical expression of thymidylate synthase (TS) and thymidine
      phosphorylase (TP) was investigated in 116 of early gastric cancer, in order to
      know whether or not these reflect malignity in an early stage. The materials
      conditioned on early gastric cancer with submucosal invasion and over 1 cm2 in
      size, were 57 with and 59 without lymph node metastasis. They were divided into
      two by the depth of invasion. The expressions of TS and TP in these group were
      compared with corresponding histopathological findings. Overall expressions of TS
      and TP were 54.3% and 34.5%, respectively. The TS-expression was not related with
      the depth of invasion and lymph node metastasis. The TP-expression, however,
      showed significant difference between with and without lymph node metastasis, and
      was so on the depth of submucosal invasion in the group without the nodal
      metastasis. Multivariate analysis showed that mucosal spread bordering 4 cm2 in
      size (p = 0.024) and lymphatic permeation (p = 0.099) in TS-expression, and lymph
      node metastasis (p = 0.041), submucosal invasion (p = 0.076) and venous
      permeation (p = 0.111) in TP-expression were the noticeable factors regarding to
      their high expression rates. Although these results were considered not to exceed
      gastric resection on the prognosis, they might be applicable as one of the
      indicators in postoperative follow-up on the minor resection of early gastric
      cancer such as EMR or local resection.

PMID- 10065096
TI  - [Treatment with 5-FU modulated by low-dose CDDP for advanced cancers and
      recurrent cases of metastasis].
AB  - Advanced gastric, colon and esophageal cancers (n = 21) were treated with 5-FU
      (250 mg) modulated by CDDP (5 mg). The reductive ratio of tumor was 6/21 (28.6%).
      Six cases of partial response (PR) were limited with no surgical treatment and
      exploratory laparotomy of all cases, and the effectiveness rate was 54.5% (6/11).
      Few side effects, such as dysfunction of bone marrow and kidney, were noted. Even
      if side effects occurred, they were mild. We concluded that excellent treatment
      with 5-FU modulated by CDDP has markedly improved the efficacy.

PMID- 10065097
TI  - [The critical appraisal of QOL questionnaire for prostate cancer patients].
AB  - BACKGROUND: Prostate cancer is a common malignancy that affects Japanese elderly
      men. Its incidence is increasing, recently, and its treatments are various. The
      measurement of quality of life (QOL) has become important for the evaluation of
      and selection of treatments. In Japan, however, there is no standard way of
      measuring QOL for prostate cancer patients, except the Japanese version of the
      EORTC QOL questionnaire for prostate cancer patients. We examined the validity
      and feasibility of this translated EORTC QOL questionnaire for prostate cancer
      patients. METHODS: Sixty-nine prostate cancer patients who were under treatment
      in 4 hospitals were selected for this study. We applied the content validity, the
      factorial validity which was analyzed by the oblique principal component cluster
      analysis, the internal consistency analyzed by the alpha coefficient of Cronbach,
      the convergent validity which was used GHQ, IPSS and PS as external measures, and
      the feasibility. RESULTS: This questionnaire showed good internal consistency, as
      the alpha coefficient was 0.61 to 0.90 in all domains, except for sex life, which
      was the lowest. This questionnaire was classified into 7 clusters by the oblique
      principal component cluster analysis. Consequently, the factorial validity was
      good, except for items regarding sex life. As domains correlate well with
      external measures except in sex life, the convergent validity was good. It was
      suggested that only two items were not acceptable in regard to the content
      validity and the feasibility, and that the translation into Japanese of 2 items
      was inadequate. CONCLUSIONS: Our study suggests that the Japanese version of the
      EORTC QOL questionnaire for prostate cancer patients demands improvement for the
      practical employment in clinical trials, as there is a problem of translation and
      feasibility.

PMID- 10065098
TI  - [A study of the safety of rapid infusion of alendronate].
AB  - To investigate the safety of rapid infusion of alendronate, we used alendronate
      therapy for 11 breast cancer patients with bone metastasis. Of the 11 patients,
      only 1 had hypercalcemia and the remaining 10 normocalcemia. Rapid infusion of
      alendronate consisted of an administration of alendronate 10 mg diluted in 100 ml
      saline in 30 minutes, and was repeated every two weeks. Each patient underwent 1
      to 9 alendronate treatments. During alendronate therapy, only one patient
      complained of general fatigue, and the remaining 10 showed no alendronate-induced
      clinical symptoms. Rapid infusion of alendronate caused an increase in BUN level
      in two patients receiving intravenous hyperalimentation (IVH), a mild increase of
      GOT level in one, and a decrease of serum phosphorus level in two receiving IVH.
      However, no increase was found in serum creatinine and GOT levels. In addition,
      no patients showed alendronate-induced hypocalcemia. In conclusion, rapid
      infusion of alendronate brings about no major adverse effects, and makes it
      easier for many patients with bone metastasis to receive alendronate therapy on
      an outpatient basis.

PMID- 10065099
TI  - [Successful treatment of metastatic bone cancer from colon with combination
      treatment (radiation and 5-FU); a case report].
AB  - An 80-year-old woman with metastatic bone cancer from ascending colon showed a
      remarkable response to combination therapy of 5-FU and radiation. 5-FU (500
      mg/day) was administered daily through intra-arterial catheter. The total dose of
      5-FU was 15.5 g. Radiotherapy was performed (total radiation dose, 45 Gy). After
      therapy, metastatic lesions were remarkably reduced in size according to various
      imaging techniques, and the serum CEA level dramatically decreased from 249 ng/ml
      to 5.2 ng/ml. Other tumor markers such as CA19-9, NSE, and CYFRA were also
      dramatically decreased. Various tumor-related symptoms, especially the pain
      caused by tumor invasion, were also decreased. Drug toxicity caused slight nausea
      and leucopenia. These results suggested that the combination therapy of 5-FU and
      radiation is useful for the pain caused by metastatic bone cancer.

PMID- 10065100
TI  - [A case of multiple liver metastases showing good response by administration of
      carmofur alone in an aged patient with colorectal cancer].
AB  - An 85-year-old woman had an elevated serum tumor marker CEA, and CT examination
      revealed multiple liver metastases. The patient was treated with oral
      administration of 200 mg/day of carmofur (HCFU) alone in our hospital. As a
      result, more than 60% of the focuses of liver metastasis disappeared, and the
      level of CEA decreased. The present case seems to show that liver metastases were
      significantly decreased by chemotherapy with oral administration of HCFU by
      itself. Thus, the case suggests that HCFU is useful for the treatment of liver
      metastases from colorectal cancer.

PMID- 10065101
TI  - [A case of hepatocellular carcinoma with tumor thrombus in the right atrium
      successfully treated by arterial administration of lipiodol-SMANCS].
AB  - In February, 1996, a 73-year-old male with liver dysfunction was admitted to our
      hospital for further examination and treatment of liver tumor. The liver tumor
      was revealed by imaging examination, which was mainly in the S4-S8 of liver with
      a thrombus growing from the right anterior branch to the right branch of the
      portal vein, and from the right hepatic vein to the inferior vena cava and right
      atrium. The serum AFP and PIVKA-II levels were elevated to 3.610 ng/ml and 54
      AU/ml, respectively. The patient was diagnosed as having hepatocellular
      carcinoma, and was treated by arterial administration of anticancer drugs
      (epirubicin hydrochloride, mitomycin C and carboplatin) and TAE. Though the main
      tumor (S4-S8 of liver) was reduced by TAE, the portal and atrial tumor thrombus
      did not respond. One month after TAE (20 May, 1996), the first arterial
      administration of Lipiodol-SMANCS was given, followed by 4 successive procedures
      with an interval of about 1.5 months (total dose 15 mg), resulting in remarkable
      tumor thrombus shrinkage and reduction of AFP levels to 80 ng/ml. This case shows
      that arterial administration of SMANCS may be one of the effective treatments for
      hepatocellular carcinoma, even with tumor thrombus of hepatic vein, IVC and right
      atrium.

PMID- 10065102
TI  - [A case of advanced gallbladder cancer responding to neoadjuvant intra-arterial
      chemotherapy].
AB  - The patient was a 52-year-old female who had been diagnosed as advanced gall
      bladder cancer by various imaging studies. The cancer responded to neoadjuvant
      intra-arterial chemotherapy and was curatively resected. Since cancer had invaded
      the median widely, the posterior and the lateral segments of the liver according
      to CT imaging, neoadjuvant chemotherapy was used. The combination chemotherapy
      included intra-arterial chemotherapy (CDDP 10 mg + 5-FU 250 mg/day/week x5 times,
      EPI 10 mg + 5-FU 250 mg/day/week x3 times) through the hepatic artery and oral
      chemotherapy (UFT 300 mg/day for 106 days). No severe side effects were found
      during this chemotherapy. Imaging studies after the chemotherapy showed a partial
      response (PR) and curative resection (hepato-pancreato-duodenectomy with regional
      lymph nodes dissection) could be performed successfully. She has been disease
      free without any sign of recurrence for 18 months after surgery. We conclude that
      this combination chemotherapy will be useful for advanced gall bladder cancer if
      the appropriate combinations, dosages, and administration routes are chosen.

PMID- 10065103
TI  - [A case of laryngeal cancer treated for over 2 years with UFT and CBDCA alone].
AB  - A patient with early laryngeal cancer who rejected both radiation therapy and
      surgery was treated with only chemotherapy of UFT combined with CBDCA. UFT
      (tegafur 300 mg/day) was administered orally and CBDCA was injected intravenously
      at a dose of 300 mg/body every 1-2 months, 11 times. For over 2 years the patient
      has demonstrated gradual tumor growth, but has not complained of dyspnea and has
      worked every day. The chemotherapy has improved his quality of life.

PMID- 10065104
TI  - [A case of carcinoma of lower lip showing excellent response to chemotherapy with
      UFT].
AB  - We report a case of squamous cell carcinoma of the lower lip showing an excellent
      response to chemotherapy with UFT. A 68-year-old woman with a painless swelling
      of her lower lip was refereed to our service. This tumor was 19 x 18 mm with
      cauliflower surface, and induration was noted around the mass. The pathological
      diagnosis was squamous cell carcinoma of well-differentiated type. After
      chemotherapy with UFT (400 mg/day), the tumor became flat. It was then removed
      with a 7 mm-safety margin and the lower lip was reconstructed with an Abbe
      Estlandar flap from the upper lip. Post-operative histological findings indicated
      a complete response. Wound healing was uneventful, and there has been no evidence
      of recurrence for these 6 months after the operation. This case is still under
      observation.

PMID- 10065105
TI  - [A case of pleural and mediastinal lymph node metastases from breast cancer
      effectively treated with fadrozole hydrochloride in combination with
      cyclophosphamide].
AB  - A 63-year-old woman was diagnosed with pleural and mediastinal lymph node
      metastases 116 months after operation because of bilateral breast cancer. She was
      then treated with fadrozole hydrochloride (FH) (2 mg). Adriamycin (30 mg)
      administration into the pleural cavity was attempted, but did not prove
      effective. Thus, we tried to combine FH with cyclophosphamide (100 mg). After one
      month, chemoendocrine therapy relieved her complaints of cough and shortness of
      breath. CT revealed a remarkable decrease of pleural effusion and disappearance
      of mediastinal lymph nodes. She was alive 9 months after the treatment. Fadrozole
      hydrochloride in combination with cyclophosphamide is promising as an effective
      treatment in postmenopausal patients.

PMID- 10065106
TI  - [Effective treatment of AFP-producing lung cancer with UFT].
AB  - The main form of chemotherapy for non small cell lung cancer is a multiple
      combination therapy centered on cisplatin (CDDP). We herein report a case in
      which a favorable course was obtained for a patient with extremely rare AFP
      producing lung cancer by single oral administrations of UFT, following
      extirpation of brain metastasis. The patient was an 80-year-old male whose main
      complaints were headache and aphasia. Following close examination, a diagnosis
      was made of moderately differentiated adenocarcinoma with the primary lesion in
      S6 of the right lung. A metastatic lesion was found in the left occipital lobe.
      Blood AFP was an abnormally high 17,000 ng/ml. No tumorous lesions were found in
      the liver. The brain metastasis were extirpated to alleviate cranial nerve
      symptoms, and the tissue was found to be the same as that of the primary lesion.
      AFP staining of the tumor tissue revealed positive cells. Because there was
      proliferation in the primary tumor following surgery, administration of UFT (300
      mg/day Tegafur) was begun. Four weeks later the tumor had begun to shrink, and at
      15 weeks was judged to be a partial response. A reduction in AFP was also seen.
      The patient showed absolutely no side effects from UFT, thus enabling outpatient
      treatment. Good results were obtained both in reducing the tumor and in
      maintaining the patient's quality of life.

PMID- 10065107
TI  - [A case of metastatic liposarcoma originating in the retroperitoneum successfully
      treated with combination chemotherapy].
AB  - We reported a 36-year-old woman with metastatic liposarcoma originating in the
      retroperitoneum, which responded well to adjuvant chemotherapy. The primary tumor
      was removed by surgery. Two months later, the patient developed metastasis to the
      brain, and to the lung four months later. Metastatic liposarcomas to the brain
      generally are extremely rare. The patient was treated with combination
      chemotherapy using cyclophosphamide, vincristine, adriamycin, and dacarbazine
      (CYVADIC). After she was examined, the former two drugs were alternated with
      vindesine and ifosfamide, and another regimen with cisplatin and etoposide was
      given after a three-week interval. As a result, both of the metastases totally
      disappeared. No recurrent lesion has been noted for two years. Although the role
      of chemotherapy for liposarcoma has not been well defined and little data support
      its use in an adjuvant setting, this combination chemotherapy seemed to be
      effective for advanced liposarcoma.

PMID- 10065108
TI  - [Measurement of PyNPase and analysis on correlation between breast cancer tissue
      and lymph node].

PMID- 10065109
TI  - [Non-clinical studies of gemcitabine--the mode of action and antitumor
      activities].
AB  - Gemcitabine (2', 2'-difluorodeoxycytidine: dFdC) is a nucleoside analogue of
      deoxycytidine (dCyd). In the cells, dFdC is rapidly phosphorylated by dCyd
      kinase. dFdC inhibits ribonucleotide reductase and the subsequent decrease in
      cellular deoxynucleotides (particularly dCTP) is an important self-potentiating
      mechanism, resulting in decreased dFdC nucleotide incorporation into DNA. Other
      self-potentiating mechanisms of dFdC include increased formation of active dFdCDP
      and dFdC TP, and decreased elimination of dFdC nucleotides. After dFdC nucleotide
      is incorporated on the end of the DNA strand, one more deoxynucleotide is added
      and thereafter the DNA polymerases are unable to proceed (masked chain
      termination). dFdC is a better transport substrate compared with Ara-C,
      phosphorylated more efficiently and eliminated more slowly. These differences
      together with self-potentiation, masked chain termination and the inhibition of
      ribonucleotide reductase may explain why dFdC is active against human solid
      cancers compared with Ara-C. Schedule-dependent antitumor activities of dFdC were
      observed against various rodent tumors and human cancer xenograft systems.

PMID- 10065110
TI  - [Experimental model for cancer metastasis].
AB  - It is important for metastasis research to establish a good experimental model
      for cancer metastasis. The author has introduced a variety of in vitro and in
      vivo models for cancer metastasis, and suggested how to select them for
      individual metastasis research.

PMID- 10065111
TI  - Allogeneic bone marrow transplantation for severe aplastic anemia: the Hong Kong
      scenario.
AB  - Severe aplastic anemia (SAA) is a disease associated with high mortality. For
      young patients with HLA identical siblings, allogeneic bone marrow
      transplantation (BMT) offers the best chance of cure. Favourable results have
      also been reported using immunosuppressive therapy (IST). Transplantation is
      usually favoured for patients below 45 years of age. We report our experience of
      11 allogeneic and one syngeneic BMT for adult Chinese patients with SAA, over a 4
      year period from 1991 to 1995. Ten of the 12 (83 per cent) patients had received
      and failed prior IST including anti-thymocyte globulin (ATG) before being
      referred for BMT. Neutrophil and platelet engraftment was successful in 11 of
      them (92 per cent) and nine were completely transfusion independent after
      transplantation. Their overall 3-year survival was 67 per cent. The compromised
      overall result was due to a number of cases transplanted after a long time delay.
      No patient transplanted beyond 3 years from the initial time of diagnosis of SAA
      achieved long-term marrow engraftment, and they all eventually succumbed. On
      univariate analysis, a longer time delay and hence a larger amount of blood
      products exposure, were highly significantly statistically associated with
      inferior marrow engraftment and patient survival. Other factors including age,
      iron status, infused cell dose and the conditioning protocol were not found to
      significantly affect engraftment and survival. Graft versus host disease was
      clinically mild or absent in most patients. This may be related to ethnicity or
      previous ATG exposure. In conclusion, early allogeneic BMT was a safe and
      effective treatment in our small series of patients with SAA failing IST.

PMID- 10065112
TI  - Liposomal daunorubicin: in vitro and in vivo efficacy in multiple myeloma.
AB  - Liposomal encapsulation of anthracyclines is a potential method of drug
      targeting, altering both the antitumour activity and side-effect profile of
      anthracyclines. Liposomal daunorubicin (daunoxome) shows both altered
      pharmacokinetics and a potential for reducing dose-limiting cardiotoxicity
      compared to conventional daunorubicin. Anthracyclines have a common role in the
      treatment of multiple myeloma, a prevalent and fatal haematological malignancy.
      Avoiding cumulative anthracycline toxicity in these patients is important. There
      is also a need for more effective relapse schedules given that many patients have
      chemosensitive disease at relapse. We have analysed daunoxome in vitro in myeloma
      cell lines using a thymidine-based cytotoxicity assay and show superior efficacy
      compared to a pegylated liposomal doxorubicin derivative. Subsequently we have
      treated seven relapsed myeloma patients with a regime consisting of oral CCNU 25
      50 mg/m2 on day 1, 4 days of oral dexamethasone 10 mg/m2 and intravenous
      daunoxome (liposomal daunorubicin) given for 4 days (total 100 mg/m2). The main
      toxicity was myelosuppression but non-haematological toxicity was minimal and the
      regime was well tolerated. Four out of seven of these heavily pretreated patients
      responded. Together with the in vitro data on its cytotoxicity in myeloma and its
      favourable pharmacokinetic profile further studies of liposomal daunorubicin in
      myeloma would be warranted.

PMID- 10065113
TI  - Stimulatory effects of neopterin on hematopoiesis in vitro are mediated by
      activation of stromal cell function.
AB  - The pteridine neopterin (NP) was shown to be produced by monocytes and is known
      to be a useful marker of immunological activation, although, its biological
      activity is still unclear. Recently, we found that intravenous administration of
      NP increased the numbers of blood leukocytes, and granulocyte-macrophage
      progenitor cells (CFU-GM) in the bone marrow and spleens of mice. In order to
      elucidate the mechanism whereby NP stimulates hematopoiesis, the effects of NP on
      hematopoietic stem cell proliferation and differentiation in vitro were studied
      using a long-term bone marrow culture (LTMC) system with cloned stromal cell
      line, MS-5. Adding NP to the LTMC increased the numbers of cells in total, CFU-GM
      and colony-forming unit in spleen (CFU-S). NP also increased the number of CFU-GM
      in a soft agar culture system, but it did not enhance CFU-GM colony formation
      when target bone marrow cells were semi-purified (T, B and adherent cell-depleted
      bone marrow cells) and cultured in this system, suggesting that NP did not
      directly affect the proliferation of hematopoietic progenitors. Conditioned
      medium obtained from NP-treated stromal cells had much greater colony-stimulating
      activity than that obtained from untreated stromal cells. Furthermore, NP
      treatment stimulated the production of IL-6 and GM-CSF by stromal cells. All
      these findings suggest that NP stimulates hematopoietic cell proliferation and
      differentiation in vitro by activating stromal cell function.

PMID- 10065114
TI  - Circulating CD34+ counts and apheresis planning.
AB  - The success of peripheral blood progenitor cell (PBPC) transplantation depends
      upon harvesting adequate numbers of cells and accurate prediction of when to
      commence apheresis. Although peripheral white cell count (WBC) is commonly used
      to identify when to initiate apheresis it does not uniformly predict the CD34+
      content of the apheresis product nor the number of exchange procedures required.
      We investigated whether the peripheral blood CD34+ count would not only predict
      harvest yield but whether it would also predict the number of apheresis
      procedures needed to generate at least 2 x 10(6)/kg CD34+ cells. CD34+ counts
      were performed over an 8-month period on the peripheral blood and PBPC harvests
      of all patients undergoing leucopheresis. Regression analysis showed a highly
      significant correlation between peripheral blood CD34+ count and yield of CD34+
      cells in the apheresis product. The regression plot with WBC was weaker. We have
      shown that a peripheral CD34+ count > or = 62 x 10(6)/l is required to
      confidently achieve an adequate harvest in one apheresis, two aphereses are
      needed if the initial count is > or = 40 x 10(6)/l. Therefore peripheral blood
      CD34+ counts not only are able to determine the threshold at which to commence
      apheresis but are useful in predicting apheresis requirements and planning
      demands on the apheresis service.

PMID- 10065115
TI  - Recent publications in hematological oncology.

PMID- 10065116
TI  - Sceptical medicine.

PMID- 10065117
TI  - Accidental drug toxicity associated with methadone maintenance treatment.

PMID- 10065118
TI  - Confusion about secondary prevention for bowel cancer: resolving issues at the
      front line.

PMID- 10065120
TI  - Mortality associated with New South Wales methadone programs in 1994: lives lost
      and saved.
AB  - OBJECTIVES: To estimate the effects of methadone programs in New South Wales on
      mortality. DESIGN AND CASES: Retrospective, cross-sectional study of all 1994 New
      South Wales coronial cases in which methadone was detected in postmortem
      specimens taken from the deceased. Cases were people we identified as patients in
      NSW methadone maintenance programs or those whose deaths involved methadone syrup
      diverted from maintenance programs. OUTCOME MEASURES: Relative risks of fatal,
      accidental drug toxicity in the first two weeks of treatment and later; the
      number of lives lost as a result of maintenance treatment; preadmission risks and
      the number of lives saved by maintenance programs, calculated from data from a
      previous study. RESULTS: There was very close agreement between this study's
      classifications and official pathology reports of accidental drug toxicity. The
      relative risk (RR) of fatal accidental drug toxicity for patients in the first
      two weeks of methadone maintenance was 6.7 times that of heroin addicts not in
      treatment (95% CI RR, 3.3-13.9) and 97.8 times that of patients who had been in
      maintenance more than two weeks (95% CI RR, 36.7-260.5). Despite 10 people dying
      from iatrogenic methadone toxicity and diverted methadone syrup being involved in
      26 fatalities. In 1994, NSW maintenance programs are estimated to have saved 68
      lives (adjusted 95% CI, 29-128). CONCLUSIONS: In 1994, untoward events associated
      with NSW methadone programs cost 36 lives in NSW. To reduce this mortality,
      doctors should carefully assess and closely monitor patients being admitted to
      methadone maintenance and limit the use of takeaway doses of methadone.

PMID- 10065121
TI  - Australian general practitioners' views and use of colorectal cancer screening
      tests.
AB  - OBJECTIVES: To determine general practitioners' (GPs) current beliefs, knowledge
      and self-reported practices of screening for colorectal cancer. DESIGN AND
      SETTING: Postal survey of national random sample of 1271 GPs in 1996. OUTCOME
      MEASURES: GP views on effectiveness of faecal occult blood testing (FOBT) and
      flexible sigmoidoscopy in reducing premature death from colorectal cancer in
      "average-risk" patients (asymptomatic with no family history); views on frequency
      of tests and target group; use of these tests; and independent predictors of
      views and use. RESULTS: Response rate was 67%. FOBT and flexible sigmoidoscopy
      were said to be effective as screening tests by 38% and 61% of GPs, respectively,
      but 30% and 25% were unsure. Independent predictors of belief in screening
      effectiveness were State of practice (for FOBT), male sex and awareness of Gut
      Foundation guidelines (for flexible sigmoidoscopy) and increasing age (for both).
      Most often chosen screening frequencies were every year for FOBT (29%), and five
      yearly for flexible sigmoidoscopy (24%), although 19% and 26%, respectively, were
      unsure of the appropriate screening interval. Most often cited target group was
      people aged over 40 years with first-degree relatives with colorectal cancer: 63%
      of GPs would offer FOBT and 74%, flexible sigmoidoscopy. Fewer than 3% of GPs
      were likely to adopt an opportunistic approach to screening, yet 15% would be
      highly likely to recommend FOBT during a dedicated health check-up for a 58-year
      old male patient, and 9% for a female patient. CONCLUSION: The absence to date of
      a coherent national policy on colorectal cancer screening is associated with wide
      variations in views and practice that are inconsistent with the available
      evidence. If GPs are to be involved in implementing population screening,
      national policy must be widely and effectively promulgated.

PMID- 10065122
TI  - Australian national birthweight percentiles by gestational age.
AB  - OBJECTIVE: To develop national birthweight percentiles by gestational age for
      male and female singleton infants born in Australia, and to compare the
      birthweight percentiles of Indigenous and non-Indigenous infants. DESIGN AND
      SETTING: Cross-sectional study of singleton live births to Australian-born
      mothers from 1991 to 1994. MAIN OUTCOME MEASURES: Birthweight percentiles by
      gestational age. RESULTS: During 1991-1994 Australian-born women gave birth to
      769,077 live singleton infants. Of these, 28,230 (3.7%) were reported as births
      to Aboriginal or Torres Strait Islander women. Birthweight was missing for 581
      (0.1%) births and gestational age was missing for 3014 (0.4%). An additional 3283
      (0.4%) births were excluded because the recorded birthweights were extreme
      outliers for their recorded gestational ages. Indigenous women were more likely
      to be recorded as giving birth preterm (< 37 weeks' gestation) than non
      Indigenous women (11.6% v. 5.4%) and were more likely to give birth to small-for
      gestational-age infants at term. After 34 weeks' gestation, the median
      birthweights of Indigenous infants were consistently lower than those of non
      Indigenous infants. At 40 weeks' gestation the difference in the median
      birthweights between these two groups was 160 g for males and 130 g for females.
      CONCLUSIONS: We present recent birthweight percentiles by gestational age based
      on national data in Australia. These percentiles provide current Australian norms
      for clinicians and researchers, and can provide a baseline for monitoring
      Indigenous perinatal outcomes.

PMID- 10065123
TI  - Ceiling fan injuries: the Townsville experience.
AB  - From 1 April 1995 to 31 March 1997, 50 people presented to Townsville General
      Hospital with injuries caused by ceiling fans. Injuries ranged from grazes to
      compound skull fractures, and seven patients required admission to hospital for
      ongoing treatment. Most of these injuries could have been avoided. Current safety
      guidelines for the use of ceiling fans are inadequate.

PMID- 10065124
TI  - Quality in healthcare in the United Kingdom: lessons for Australia.
AB  - The United Kingdom has a strong emphasis on quality in healthcare and clinical
      audit. Many quality activities are funded by the government but managed by
      professional bodies, a model that should be trialed in Australia.

PMID- 10065125
TI  - Should medical students read Plato?
AB  - In the United Kingdom, the General Medical Council has recommended that the
      medical curriculum should consist of a core of basic medical courses plus special
      study modules drawn from both medical and non-medical disciplines. One such study
      module at Glasgow University brought medical students together with arts students
      to study moral and political philosophy through a reading of Plato's Republic.

PMID- 10065126
TI  - Heroin addiction: the science and ethics of the new treatment pluralism.
AB  - As approaches to treating heroin addiction grow in number, their ethics and their
      meaningful contribution to the science in this field need more careful
      consideration.

PMID- 10065127
TI  - Advances in gastrointestinal endoscopy.
AB  - Endoscopy has a rapidly expanding role in diagnosis and management of
      gastrointestinal disease.

PMID- 10065128
TI  - Accidental illicit drug deaths in Sydney: how common are they?

PMID- 10065129
TI  - Another PMA-related fatality in Adelaide.

PMID- 10065130
TI  - Midline mamillary body fusion: incidental finding or pathological lesion?

PMID- 10065131
TI  - SSRI antidepressants are effective for treating delusional hypochondriasis.

PMID- 10065132
TI  - Re-engineering the elective surgical service of a tertiary hospital: a historical
      controlled trial.

PMID- 10065133
TI  - Neutropenia associated with omeprazole.

PMID- 10065134
TI  - Outcome measures of an Australian breast-screening program.

PMID- 10065135
TI  - Spina bifida and folate.

PMID- 10065136
TI  - Spina bifida and folate.

PMID- 10065137
TI  - Women's satisfaction with general practice consultations.

PMID- 10065138
TI  - [Stereotactic one-time irradiation (radiosurgery). The methods, indications and
      results].
AB  - BACKGROUND: Stereotaxy is a method to determine a point in the patient's body by
      an external coordinate system which is attached to the patient. Radiosurgery uses
      this method for precise delivery of a high single radiation dose to the patient.
      The aim is to destroy the tissue in the target and to spare surrounding
      unaffected normal tissue by a steep dose gradient. METHODS: Three techniques of
      percutaneous radiosurgery are available: radiosurgery with ion beams with a
      cyclotron, spherical arrangement of cobalt-60 sources, the so-called gamma knife,
      and an adapted linear accelerator. The availability and the good clinical
      experience lead to a wide spread use of linear accelerator for radiosurgery in
      recent years. A subsequent development is fractionated stereotactic radiotherapy
      which combines the precision of radiosurgery with the radiobiological advantage
      of fractionation. RESULTS: Only a few indications for radiosurgery are proven by
      statistically valid studies. One of these is the treatment of small arteriovenous
      malformation, where obliteration rates of 80% to 100% are reported with only
      minor toxicity. However, the obliteration rate is reduced significantly in large
      arteriovenous malformations. A local control rate of 90% is obtained after
      radiosurgery of brain metastases which is comparable to the results of
      microsurgical resection followed by adjuvant whole brain radiotherapy. An ongoing
      EORTC study evaluates the role of adjuvant whole brain radiotherapy after
      radiosurgery. The survival of the patients with brain metastases is limited by
      the existence of progressive extracerebral disease. The role of radiosurgery in
      the treatment of benign tumors is currently evaluated in clinical studies which
      include: vestibular schwannomas, meningiomas, chordomas and chondrosarcomas and
      pituitary adenomas. Most of the published studies include only small tumors
      because radiosurgery is limited by the risk of radionecrosis of adjacent normal
      tissue, which shows a steep dose volume response relationship. Recent
      developments of stereotactic radiotherapy include the use of mini-multileaf
      collimators and clinical studies on stereotactic radiotherapy of extracranial
      targets. CONCLUSIONS: Stereotactic irradiation is a well established treatment
      technique for intracranial tumors and arteriovenous malformations. Methods are
      available that allow optimization of dose distributions to irregularly shaped
      tumors for single dose as well as fractionated stereotactic irradiations by
      linear accelerator. Therefore the therapeutic potential of this technique has
      increased and enables also the extracerebral application in controlled clinical
      studies.

PMID- 10065139
TI  - Salivary gland protection by amifostine in high-dose radioiodine therapy of
      differentiated thyroid cancer.
AB  - BACKGROUND: Salivary gland impairment following high-dose radioiodine treatment
      is a well-recognized side effect, in general caused by free radicals. Therefore,
      it seemed promising to evaluate the radioprotective effect of the radical
      scavenger amifostine in patients receiving high-dose radioiodine therapy.
      PATIENTS AND METHOD: Quantitative salivary gland scintigraphy using 100 to 120
      MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid
      cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight
      patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine
      treatment and compared retrospectively with 9 control patients. Xerostomia was
      graded according to WHO criteria. RESULTS: In 9 control patients high-dose
      radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate
      uptake by 35.4 +/- 22.0% and 31.7 +/- 21.1% in parotid and submandibular glands,
      respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In
      contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878)
      decrease in parenchymal function following high-dose radioiodine treatment, and
      xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage in
      salivary glands induced by high-dose radioiodine treatment can be reduced
      significantly by amifostine. This may help to increase patients' quality of life
      in differentiated thyroid cancer.

PMID- 10065140
TI  - [The role of radiotherapy in the treatment of malignant meningiomas].
AB  - PURPOSE: Most malignant meningiomas will recur following surgical resection only.
      The role of irradiation and radiation dose levels is poorly defined. This study
      reviews a single institution experience using both, conventional and high doses >
      or = 60 Gy/CGE radiation regimen. PATIENTS AND METHODS: Between 1974 and 1995 16
      patients with histologically proven malignant meningioma underwent radiation
      therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years).
      Three patients reported previous irradiation to the head at least 14 years prior
      to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent
      disease. Six patients underwent gross total and 10 patients subtotal resection
      (Table 1). RT was delivered using conventional, megavoltage photons or combined
      160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the
      radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent)
      (median: 58 Gy/CGE, Table 2). RESULTS: With median observation time of 59 months
      (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were
      52% and 17%, respectively. Target doses > or = Gy/CGE resulted in significantly
      improved tumor control (100%) compared to < 60 Gy/CGE (17%) (p = 0.0006, Table 3
      and Figure 1). Improved local control translated also in increased overall
      survival: 87% (> or = 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025,
      Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients
      developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. CONCLUSION:
      Conformal, radiation therapy with target doses > or = 60 Gy/CGE, in this study by
      use of combined proton and photon irradiation, can significantly improve chances
      of long-term local control and survival for patients diagnosed with these
      challenging tumors.

PMID- 10065141
TI  - [A comparison of CT-supported 3D planning with simulator planning in the pelvic
      irradiation of primary cervical carcinoma].
AB  - BACKGROUND: Using standardized simulator planning guided by bony landmarks for
      pelvic irradiation of primary cervical carcinoma with some patients a
      geographical miss regarding tumor or potential tumor spread can happen because of
      insufficient knowledge of the individual anatomical situation. The question
      arises whether for patients with this indication the higher effort in terms of
      time and personnel for 3D treatment planning is justified. PATIENTS AND METHOD:
      In a prospective study on 20 subsequent patients with primary cervical carcinoma
      in Stages I to III simulator planning of a 4-field box-technique was performed.
      After defining the planning target volume (PTV) in the 3D planning system the
      field configuration of the simulator planning was transmitted. The resulting plan
      was compared to a second one based on the defined PTV and evaluated regarding a
      possible geographical miss and encompassment of the PTV by the treated volume
      (ICRU). Volumes of open and shaped portals were calculated for both techniques.
      RESULTS: Planning by simulation resulted in 1 geographical miss and in 10 more
      cases the encompassment of the PTV by the treated volume was inadequate. For a
      PTV of mean 1,729 cm3 the mean volume defined by simulation was 3,120 cm3 for the
      open portals and 2,702 cm3 for the shaped portals (Figure 1). The volume
      reduction by blocks was 13.4% (mean). With CT-based 3D treatment planning the
      volume of the open portals was 3.3% (mean) enlarged to 3,224 cm3 (Figure 2). The
      resulting mean volume of the shaped portals was 2,458 ccm. The reduction compared
      to the open portals was 23.8% (mean). The treated volumes were 244 cm3 or 9%
      (mean) smaller compared to simulator planning. The "treated volume/planning
      target volume ratio" was decreased from 1.59 to 1.42. CONCLUSION: The
      introduction of 3D treatment planning for pelvic irradiation of cervical
      carcinoma is to be recommended for reasons of quality assurance. Reduction of the
      treated volume is possible but further research has to be done to determine
      whether the rate of complications can be decreased as well.

PMID- 10065142
TI  - The influence of field size and other radiotherapy parameters on acute toxicity
      in pharyngolaryngeal cancers.
AB  - BACKGROUND: Accelerated radiotherapy and/or chemo-radiotherapy of the head and
      neck region decrease the tolerance of acute responding tissues. Tissue tolerance
      is also field size dependent. PATIENTS AND METHOD: An attempt to retrospectively
      quantify the risk of acute toxicity (peak scores) with field size was undertaken
      in 286 patients irradiated for unresected head and neck tumors with or without
      chemotherapy, and with or without accelerated radiotherapy between 1979 and 1990.
      A Grade-3 to -4 acute toxicity score (RTOG) and > 5% weight loss were chosen as
      endpoints. RESULTS: For Grade-3 to -4 toxicity, the risk increased from 0.06 for
      5 x 5 cm2 to 0.68 for 17 x 17 cm2 fields and conventional radiotherapy, and from
      0.33 for 5 x 5 cm2 to 0.94 for 17 x 17 cm2 and multiple daily fractionation. For
      > 5% weight loss, the risk ranged from 0.07 for 5 x 5 cm2 to 0.94 for 17 x 17 cm2
      fields. CONCLUSIONS: The size of the cervical fields receiving the first 50 Gy
      was an indicator for severe acute toxicity and weight loss. Taking these data
      into account may help to improve preventive and treatment measures.

PMID- 10065143
TI  - [The intensification of the radiotherapeutic effect on HeLa cells by
      gemcitabine].
AB  - BACKGROUND: Gemcitabine (2'.2'-difluorodeoxycytidine; dFdC) is a new nucleoside
      analog with promising activity in different solid tumors in vivo and in vitro. As
      published up to now, combined with irradiation dFdC demonstrates a
      radiosensitizing effect on pancreas and colon carcinoma cell lines. We
      investigated the influence of dFdC on the radiosensitization of human squamous
      carcinoma cells of the cervix (HeLa-cells, ATCC CCL-2). MATERIAL AND METHODS:
      Under standardized conditions monolayer cultures of HeLa-cells were incubated in
      medium with dFdC for different times (4 to 24 hours) and exposed to different
      concentrations (0.003, 0.01 and 0.03 mumol/l). Irradiation (2 to 6 Gy, electron
      beam) followed immediately or 12 hours after dFdC-exposure. Cell survival was
      determined by colony forming assay. Using the linear-quadratic model cell
      survival curves were fit after correction for drug-induced cytotoxicity and the
      mean inactivation dose (MID) was calculated. Radiation enhancement was defined as
      the ratio MIDRT(= Control)/MIDRT + dFdC > 1. RESULTS: Exposed to gemcitabine for
      4 and 8 hours and followed by immediate irradiation the radiation enhancement
      ratio (Table 1) is 1.07 to 1.14 and 1.04 to 1.22, respectively, if dFdC
      concentration is > or = 0.01 to 0.03 mumol/l. Further increase of the irradiation
      effect is demonstrated in cells exposed to > or = 0.003 to 0.03 mumol/l dFdC for
      16 and 24 hours (radiation enhancement ratio 1.08 to 2.0 and 1.08 to 2.48,
      respectively) (Figure 3). If irradiation is applied 12 hours after 24-hour
      exposure (0.01 and 0.03 mumol/l) the enhancement ratio was 1.18 and 1.7,
      respectively (Figure 4). CONCLUSIONS: In cell cultures the assays combining
      irradiation with dFdC demonstrate that dFdC is a potent radiation sensitizer of
      HeLa-cells. The effect of irradiation on cells pre-treated with non- and hardly
      cytotoxic concentrations of dFdC is increased in dependence of dose and time of
      exposure.

PMID- 10065144
TI  - [Is tamoxifen effectively preventive against breast carcinoma?].

PMID- 10065145
TI  - [A randomized phase-II study of high-dosage chemotherapy with stem-cell
      transplantation in women with operable infraclavicular metastatic breast
      carcinoma].

PMID- 10065146
TI  - [Organ preservation in bladder carcinoma by chemotherapy and TUR].

PMID- 10065147
TI  - Introduction: p53--the first twenty years.
AB  - The p53 protein was discovered 20 years ago, as a cellular protein tightly bound
      to the large T oncoprotein of the SV40 DNA tumour virus. Since then, research on
      p53 has developed in many exciting and sometimes unexpected directions. p53 is
      now known to be the product of a major tumour suppressor gene that is the most
      common target for genetic alterations in human cancer. The nonmutated wild-type
      p53 protein (wtp53) is often found within cells in a latent state and is
      activated in response to various intracellular and extracellular signals.
      Activation involves an increase in overall p53 protein levels, as well as
      qualitative changes in the protein. Upon activation, wtp53 can induce a variety
      of cellular responses, most notable among which are cell cycle arrest and
      apoptosis. To a great extent, these effects are mediated by the ability of p53 to
      activate specific target genes. In addition, the p53 protein itself possesses
      biochemical functions which may facilitate DNA repair as well as apoptosis. The
      role of p53 in normal development and particularly in carcinogenesis has been
      elucidated in depth through the use of mouse model systems. The insights provided
      by p53 research over the years are now beginning to be utilized towards better
      diagnosis, prognosis and treatment of cancer.

PMID- 10065148
TI  - The dual role model for p53 in maintaining genomic integrity.
AB  - The tumour suppressor p53 is a potent mediator of cellular responses against
      genotoxic insults. In this review we describe the multiple functions of p53 in
      response to DNA damage, with an emphasis on p53's role in DNA repair. We
      summarize data demonstrating that p53 actively participates in various processes
      of DNA repair and DNA recombination via its ability to interact with components
      of the repair and recombination machinery, and by its various biochemical
      activities. An important aspect in evaluating p53 functions is provided by the
      finding that the core domain of p53 harbours two mutually exclusive biochemical
      activities, sequence-specific DNA binding required for its transactivation
      function, and 3'-5' exonuclease activity, possibly involved in aspects of DNA
      repair. Based on the finding that modifications of p53 which lead to activation
      of its sequence-specific DNA-binding activity result in inactivation of its 3'-5'
      exonuclease activity, we propose that p53 exerts its functions as a 'guardian of
      the genome' at various levels: in its noninduced state, p53 should not be
      regarded as a 'dead' protein but, for example, via its exonuclease activity might
      be actively involved in prevention and repair of endogenous DNA damage. Upon
      induction through exogenous DNA damage, p53 will exert its well-documented
      functions as a superior response element in various types of cellular stress.
      This dual role model for p53 in maintaining genomic integrity significantly
      enhances p53's possibilities as a guardian of the genome.

PMID- 10065149
TI  - Mechanisms of p53-mediated apoptosis.
AB  - The loss of p53-mediated apoptosis (programmed cell death) has been implicated as
      an important event in tumour progression in a number of systems. p53 can induce
      or potentiate apoptosis through several mechanisms, both by regulating the
      expression of genes which can participate in the apoptotic response and through
      transcriptionally independent means. There appears to be cell type variability in
      both the response to p53 expression and in the requirement for p53
      transcriptional transactivation for the induction of apoptosis. It seems clear,
      however, that the induction of p53 in untransformed cells is more likely to
      result in cell-cycle arrest, whereas the expression of p53 in their transformed
      counterparts is more likely to result in the induction of apoptosis, and this
      may, in part, reflect the deregulated expression of E2F-1 in tumour cells. The
      synergistic action of p53 and E2F-1 in the induction of apoptosis has raised the
      possibility that the reactivation of p53 in transformed cells can be an effective
      tumour therapy.

PMID- 10065150
TI  - p53 in embryonic development: maintaining a fine balance.
AB  - In addition to its role as a tumour suppressor and cell-cycle checkpoint control
      protein, p53 has been implicated as an important protein in embryonic
      development. Despite the viability of most p53 null mice, evidence has
      accumulated that p53 may regulate differentiation and the response of embryonic
      cells to diverse environmental stresses. Moreover, it appears that maintenance of
      a fine balance of p53 protein levels within embryonic cells is important for
      optimal development. Inappropriate overexpression or underexpression of p53 can
      lead to embryonic lethality or increased risk of malformations. The p53 protein
      may utilize multiple functional activities in its regulation of developmental
      processes.

PMID- 10065151
TI  - The role of p53 in tumour suppression: lessons from mouse models.
AB  - The use of mouse models has greatly contributed to our understanding of the role
      of p53 in tumour suppression. Mice homozygous for a deletion in the p53 gene
      develop tumours at high frequency, providing essential evidence for the
      importance of p53 as a tumour suppressor. Additionally, crossing these knockout
      mice or transgenic expression p53 dominant negative alleles with other tumour
      prone mouse strains has allowed the effect of p53 loss on tumour development to
      be examined further. In a variety of mouse models, absence of p53 facilitates
      tumorigenesis, thus providing a means to study how the lack of p53 enhances
      tumour development and to define genetic pathways of p53 action. Depending on the
      particular model system, loss of p53 either results in deregulated cell-cycle
      entry or aberrant apoptosis (programmed cell death), confirming results found in
      cell culture systems and providing insight into in vitro function of p53.
      Finally, as p53 null mice rapidly develop tumours, they are useful for evaluating
      agents for either chemopreventative or therapeutic activities.

PMID- 10065152
TI  - Clinical implications of p53 mutations.
AB  - The ultimate goal of basic cancer research is to provide a theoretical foundation
      for rational approaches to improve cancer therapy. Our extensive insight into the
      biology of the p53 tumour suppressor and the clinical behaviour of tumours
      harbouring p53 mutations indicates that information concerning p53 will be useful
      in diagnosis and prognosis, and may ultimately produce new therapeutic
      strategies. At the same time, efforts to understand the clinical implications of
      p53 mutations have revealed conceptual and technical limitations in translating
      basic biology to the clinic. The lessons learned from p53 may lay the groundwork
      for future efforts to synthesize cancer gene function, cancer genetics and cancer
      therapy.

PMID- 10065153
TI  - Covalent and noncovalent modifiers of the p53 protein.
AB  - Despite the massive attention it has received, there is still much to learn about
      the p53 tumour suppressor protein. Given that it plays complex and multiple roles
      in cells, it is not surprising that p53 is subjected to an intricate array of
      regulatory processes. p53 receives signals from cells in multiple ways, leading
      to its stabilization and activation. The functions of the protein are altered by
      phosphorylation and other covalent modifications. However, a number of proteins
      can regulate p53 function dramatically by noncovalent means. p53 is thus
      subjected to numerous signaling and regulatory pathways which we have only begun
      to decipher.

PMID- 10065154
TI  - Regulation of p53 protein function through alterations in protein-folding
      pathways.
AB  - The tumour suppressor protein p53 is a stress-activated transcription factor
      whose activity is required for regulating the cellular response to stress and
      damage. The biochemical activity of p53 as a transcription factor can be
      regulated by partner proteins affecting stability, nuclear transport, signalling
      pathways modulating phosphorylation and interactions with components of the
      transcriptional machinery. The key structural determinants of p53 protein that
      drive sequence-specific DNA binding include the core specific DNA-binding domain
      and the tetramerization domain. Flanking these domains are more evolutionarily
      divergent carboxy- and amino-terminal regulatory motifs that further modulate
      tetramerization and sequence-specific transactivation. This review will mainly
      focus on the mechanisms whereby the tetramerization domain modulates sequence
      specific DNA binding and how missense point mutations in p53 protein and the
      activity of molecular chaperones may lead to unfolding of mutant p53 tetramers in
      human tumours.

PMID- 10065155
TI  - Functions of the MDM2 oncoprotein.
AB  - The p53 protein is activated in response to physiological stress resulting in
      either a G1 arrest of cells or apoptosis. As such, p53 must be tightly regulated,
      and the MDM2 oncoprotein plays a central role in that regulatory process. The
      transcription of the Mdm2 oncogene is induced by the p53 protein after DNA
      damage, and the MDM2 protein then binds to p53 and blocks its activities as a
      tumour suppressor and promotes its degradation. These two proteins thus form an
      autoregulatory feedback loop in which p53 positively regulates MDM2 levels and
      MDM2 negatively regulates p53 levels and activity. Immediately after ultraviolet
      (UV) irradiation MDM2 messenger RNA and protein levels fall in a p53-independent
      fashion, resulting in increased p53 levels. The p53 protein is then activated as
      a transcription factor by posttranslational modification permitting p53 to
      initiate its cell-cycle arrest or apoptotic (programmed cell death) functions. At
      later times, after the repair of DNA, MDM2 levels increase in a p53-dependent
      fashion. This induction of MDM2 results in the inhibition of p53 transcriptional
      activity and the degradation of p53 protein. MDM2-p53 complexes in the nucleus
      are transported to the cytoplasm via signals present in the MDM2 protein, where
      p53 is degraded in the proteasome. Thus MDM2 acts as a nuclear-cytoplasmic
      shuttle for the p53 protein. There are many levels at which this process is
      regulated, and as such there are many places for chemotherapeutic interventions.
      The amino-terminal domain of the MDM2 protein is all that is required to bind the
      p53 protein. The MDM2 protein has additional domains and therefore may have
      additional functions. Any of these MDM2 domains may contribute to MDM2's
      activities as an oncogene independent of its inhibition of the tumour suppressor
      functions of p53. Thus MDM2 itself could be a target for cancer therapeutic
      intervention.

PMID- 10065156
TI  - Regulation of cytokinesis.
AB  - At the end of mitosis, daughter cells are separated from each other by
      cytokinesis. This process involves equal partitioning and segregation of
      cytoplasm between the two cells. Despite years of study, the mechanism driving
      cytokinesis in animal cells is not fully understood. Actin and myosin are major
      components of the contractile ring, the structure at the equator between the
      dividing cells that provides the force necessary to constrict the cytoplasm.
      Despite this, there are also tantalizing results suggesting that cytokinesis can
      occur in the absence of myosin. It is unclear what the roles are of the few other
      contractile ring components identified to date. While it has been difficult to
      identify important proteins involved in cytokinesis, it has been even more
      challenging to pinpoint the regulatory mechanisms that govern this vital process.
      Cytokinesis must be precisely controlled both spatially and temporally; potential
      regulators of these parameters are just beginning to be identified. This review
      discusses the recent progress in our understanding of cytokinesis in animal cells
      and the mechanisms that may regulate it.

PMID- 10065157
TI  - Juvenile hormone regulation of HMG-R gene expression in the bark beetle Ips
      paraconfusus (Coleoptera: Scolytidae): implications for male aggregation
      pheromone biosynthesis.
AB  - Juvenile hormone III (JH III) induces acyclic isoprenoid pheromone production in
      male Ips paraconfusus. A likely regulatory enzyme in this process is 3-hydroxy-e
      methylglutaryl-CoA reductase (HMG-R). To begin molecular studies on pheromone
      production, a 1.16-kb complementary DNA representing approximately one-third of
      I. paraconfusus HMG-R was isolated by polymerase chain reaction and sequenced.
      The predicted translation product is 59% and 75% identical to the corresponding
      portion of HMG-R from the fruit fly, Drosophila melanogaster, and the German
      cockroach, Blattella germanica, respectively. Northern blots show that topical
      application of JH III increases HMG-R transcript levels in male thoraces in an
      apparent dose- and time-dependent manner. These data support the model that JH
      III raises HMG-R transcript levels, resulting in increased activity of the
      isoprenoid pathway and de novo pheromone production.

PMID- 10065158
TI  - Ventral neural tube cells differentiate into hepatocytes in the chick embryo.
AB  - A population of ventral neural tube cells has recently been shown to migrate out
      of the hindbrain neural tube via the vagus nerve and contribute to the developing
      gastrointestinal tract. Since liver is also innervated by the vagus nerve, we
      sought to determine if these cells also migrate into the liver. Ventral neural
      tube cells in the caudal hindbrain of chick embryos were tagged with a
      replication-deficient retroviral vector containing the LacZ gene on embryonic day
      2. Embryos were processed for detection of labeled cells on embryonic day 5 and
      11. Labeled cells were seen in the liver on both days and identified as
      hepatocytes. Previously, it was believed that all hepatocytes develop from the
      gut endoderm. Results of the present study show an additional source for the
      formation of liver cells.

PMID- 10065159
TI  - Production of functional rat liver PSP protein in Escherichia coli.
AB  - An efficient Escherichia coli expression system for the production of a
      perchloric acid-soluble protein (PSP) has been constructed. Complementary DNA
      encoding PSP was inserted into an inducible bacterial expression vector pGEX-4T
      1. After the plasmid introduced into E. coli was expressed by isopropyl 1-thio
      beta-D-galaetopyranoside (IPTG), the recombinant product was purified by
      glutathione-Sepharose 4B affinity chromatography. The purified product showed the
      expected NH2-terminal sequence, but the translation inhibitory activity of this
      product was 10 times lower compared with that of authentic PSP isolated from rat
      liver.

PMID- 10065160
TI  - Expression, isolation and characterization of a mutated human plasminogen kringle
      3 with a functional lysine binding site.
AB  - Each kringle of human plasminogen (HPg) except kringle 3 (K3) exhibits affinity
      for omega-aminocarboxylic acids. Assuming that the K3 domain contains a preformed
      but nonfunctional lysine binding site (LBS), Lys311 was altered by site-directed
      mutagenesis into Asp311 in accordance with the consensus sequence of the LBS.
      Cys297 involved in the interkringle disulfide bridge was mutated into Ser297 to
      minimize dimerization and aggregation. The mutated K3 TYQ[K3HPg/C297S/K311D]DS (r
      K3mut) was expressed in Escherichia coli, isolated on an Ni2(+)-nitrilotriacetic
      acid-agarose column, refolded and purified on a lysine Bio-Gel column.
      Fluorescence titration indicates affinity of r-K3mut for omega-aminocarboxylic
      acids with the following association constants (Kass, mM-1): 5-aminopentanoic
      acid: 1.3; 6-aminohexanoic acid: 4.2; 7-aminoheptanoic acid: 0.5; trans
      (aminomethyl)cyclohexanecarboxylic acid: 12.7; p-benzylaminesulfonic acid: 11.8.
      r-K3mut exhibits an affinity similar to native and mutated (R220G, E221D) K2. The
      results indicate the presence of a preformed but nonfunctional LBS in native K3
      of HPg. We were able to demonstrate for the first time that an appropriate
      mutation in the LBS of a kringle produced a weak but distinct affinity for omega
      aminocarboxylic acids.

PMID- 10065161
TI  - Insulin activates G alpha il,2 protein in rat hepatoma (HTC) cell membranes.
AB  - Insulin action is initiated by binding to its cognate receptor, which then
      triggers multiple cellular responses by activating different signaling pathways.
      There is evidence that insulin receptor signaling may involve G protein
      activation in different target cells. We have studied the activation of G
      proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding of
      guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-35S) to plasma membrane proteins
      of HTC cells, in a dose-dependent manner. This effect was completely blocked by
      pertussis toxin treatment of the membranes, suggesting the involvement of G
      proteins of the G alpha i/G alpha o family. The expression of these G alpha
      proteins was checked by Western blotting. Next, we used blocking antibodies to
      sort out the specific G alpha protein activated by insulin stimulation. Anti-G
      alpha il,2 antibodies completely prevented insulin-stimulated GTP binding,
      whereas anti-G alpha o,i3 did not modify this effect of insulin on GTP binding.
      Moreover, we found physical association of the insulin receptor with G alpha il,2
      by copurification studies. These results further support the involvement of a
      pertussis toxin-sensitive G protein in insulin receptor signaling and provides
      some evidence of specific association and activation of G alpha il,2 protein by
      insulin. These findings suggest that G alpha il,2 proteins might be involved in
      insulin action.

PMID- 10065162
TI  - Reproductive endocrinology: quo vadis? Scientific, social, ethical and economic
      challenges.

PMID- 10065163
TI  - The impact of sleep on gonadotropin secretion.
AB  - Comparable to the period of pubertal transition, sleep also exerts profound
      effects on episodic gonadotropin secretion in adult women. During the early
      follicular phase of the menstrual cycle, a sleep-induced slowing of luteinizing
      hormone (LH) secretion occurs concurrently with a rise in LH pulse amplitude. A
      selective increase in opioidergic, but not in dopaminergic or serotoninergic
      activity may account for this decline in LH pulsatility. In addition, sleep
      reversal studies have confirmed that the presence of sleep is essential for the
      expression of this neuroendocrine function. Since pituitary gonadotropin
      responsiveness to gonadotropin-releasing hormone (GnRH) is virtually unchanged
      during sleep, the reasons for the enhanced LH pulse amplitude remain unresolved.
      This sleep-associated increase in opioidergic activity may be restricted to a
      hypothalamic site, since opiate blockade does not modify the gonadotropin
      response to GnRH stimulation. In addition, circadian variability is shown in
      terms of gonadotropin secretion in regularly cycling women; this may again
      represent sleep-associated effects on gonadotropin release. Although the
      physiological importance of sleep-associated neuroendocrine phenomena remains
      basically unexplained, the observed changes in LH secretory profiles during sleep
      in adult women suggest close functional links between the endocrine secretion and
      the rest-activity cycle of the brain.

PMID- 10065164
TI  - Involvement of growth factors in the pathophysiology of polycystic ovary
      syndrome.
AB  - The etiology of polycystic ovary syndrome (PCOS) has not yet been fully
      elucidated but involves a disruption of normal ovarian function and multisystem
      sequelae. A combination of abnormally functioning genes whose expression is
      influenced by environmental, extra-ovarian factors determines the symptoms.
      Growth factors are heavily involved in the pathophysiology, either contributing
      to or as a consequence of the arrested development of follicles, abnormal
      steroidogenesis and hyperinsulinemia. Hyperactivity of a--transforming growth
      factor (TGFa) and epidermal growth factor (EGF) may block stimulation of
      aromatase and attenuate apoptosis of follicles and other factors may interface
      with the insulin-like growth factor (IGF) system preventing arrested follicles
      from becoming atretic and preventing the selection of a dominant follicle. IGF
      binding protein concentrations are decreased by insulin, freeing biologically
      active IGF-I which augments the action of luteinizing hormone (LH) by inducing LH
      receptors, hyperactivating the enzymes P450c17a and 17,20 lyase resulting in
      hyperandrogenism. Growth hormone itself may be involved in the pathophysiology,
      as in normoinsulinemic PCOS patients it is hypersecreted and its actions on
      growth factors and their binding proteins are similar to those of insulin.

PMID- 10065165
TI  - Insulin-like growth factors in endometrial function.
AB  - Growth factors and related peptides are believed to mediate and modulate the
      actions of hormones at their target tissues through autocrine/paracrine
      mechanisms. Endometrial stromal cells produce insulin-like growth factors I and
      II (IGF-I and IGF-II) as well as the high-affinity IGF binding proteins (IGFBPs),
      whereas epithelial cells and, in a lesser amount, also stromal cells contain cell
      membrane receptors for IGFs. IGFs have proliferative, differentiative and
      metabolic effects. Estrogen stimulates IGF-I gene expression in the endometrium,
      and IGF-I is assumed to mediate estrogen action. IGF-II gene expression is
      associated with endometrial differentiation. All six high-affinity IGFBPs are
      expressed in human endometrium, the most abundant being IGFBP-1. This is secreted
      by predecidualized/decidualized endometrial stromal cells in late secretory phase
      endometrium and pregnancy decidua, i.e. under the action of progesterone. The
      primary negative regulator of IGFBP-1 expression is insulin, by inhibiting IGFBP
      1 transcription. IGFBP-1 inhibits the receptor binding and biological actions of
      IGF-I in the endometrium and in cultured human trophoblastic cells. These
      findings support the view that the IGF system has autocrine and paracrine
      functions in the regulation of endometrial proliferation and differentiation.
      After implantation, decidual IGFBP-1 may regulate IGF actions at the embryo
      endometrial interface, since trophoblast cells contain IGF receptors and express
      IGF-II, but do not express IGFBP-1. Clinical conditions that are known to
      increase the risk of endometrial cancer are all characterized by the absence of
      IGFBP-1. Thus, like unopposed estrogen, unopposed IGF-I action may also lead to
      uncontrolled endometrial proliferation and favor the development of endometrial
      cancer. The measurement of mRNAs encoding the IGF system might provide a novel
      tool to evaluate the endometrial response to endogenous and exogenous estrogens
      and progestins at the molecular level.

PMID- 10065166
TI  - Fertility and infertility in aging women.
AB  - Age is often a dominant factor for women wanting to conceive. The objective of
      this study was to examine the outcome of an in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) program in relation to
      a woman's age. Between January 1995 and June 1997 we stimulated 2511 cycles. The
      mean age of the women was 34 years, with 21.9% under 30, 45.9% between 30 and 35,
      24.5% between 36 and 39, and 7.7% over 39 years. All patients aged > or = 40
      years had day 3 serum follicle-stimulating hormone (FSH) concentrations < 20
      IU/l. The stimulation regimen consisted of 150-450 IU of human menopausal
      gonadotropin (hMG) or FSH combined with either clomiphene citrate (CC) or
      gonadotropin-releasing hormone agonist (GnRHa) in a short or long protocol. Age
      had a significantly negative effect on the stimulation and fertilization failure
      rates. The clinical pregnancy rate per transfer and the embryo implantation rate
      declined significantly from 29.4% and 18.9% in women < 30 years to 19.8% and
      14.3% in patients between 30 and 35 years, 17.1% and 9.0% between 36 and 39 years
      and to 12.8% and 7.4% in those aged > or = 40 years. The spontaneous abortion
      rate was 14.9%, 16.5%, 22.4% and 33.2%, respectively. The clinical pregnancy rate
      per transfer reflected only imperfectly the performance of the older women
      because the discharge rate during stimulation and spontaneous abortions reduced
      the 'take home baby' rate to about 7% per cycle in patients aged > or = 40 years.
      It is very important in fertility practice to recognize the major impact of
      advancing maternal age.

PMID- 10065167
TI  - Matrix metalloproteinases, prostaglandins and endothelins: paracrine regulators
      of implantation.

PMID- 10065168
TI  - Cytokines in preterm parturition.
AB  - We have proposed a model in which the initiation of human parturition in the
      presence of infection is mediated by the host response. Systemic infections such
      as pyelonephritis, or localized intrauterine maternal infections such as
      deciduitis and cervicitis, might trigger parturition via the monocyte/macrophage
      system in both maternal blood and human decidua. According to this model, labor
      is to be considered an event that occurs when the intrauterine or maternal
      environment is hostile to the well-being of the fetus, as was supported by recent
      studies. From this point of view, the initiation of preterm labor may have
      survival value.

PMID- 10065169
TI  - New peptides, hormones and parturition.
AB  - This brief review emphasizes the importance of three novel discovered factors
      produced by fetal membranes, placenta and/or by the fetus itself in regulating
      uterine contractility. We have shown that, as reported for other hormones and
      substances, nitric oxide and endothelin may influence myometrial activity in an
      autocrine/paracrine manner interacting with other well-known agents such as
      prostaglandins, oxytocin and hormones. We also demonstrated that different
      isoforms of nitric oxide synthase (NOS) may play different roles throughout
      gestation and during labor. We have suggested that another peptide produced by
      trophoblast cells, adrenomedullin, may affect, directly or indirectly, myometrial
      contractility during pregnancy, although much remains to be learned about the
      mechanisms controlling adrenomedullin expression by the feto-placental tissues
      cells during pregnancy. Continued research is necessary to better define the
      complex interactions that result in parturition, both at term and preterm, and to
      allow a more rational approach to management of the premature labor, exploring
      new possible pharmacological solutions.

PMID- 10065170
TI  - Male erectile dysfunction.

PMID- 10065171
TI  - Management of male erectile dysfunction: a review.
AB  - Male erectile dysfunction is common although some patients are embarrassed and
      delay seeking medical advice. Recent improvements in the understanding of the
      anatomy, physiology and pharmacotherapy of penile erections, and the introduction
      of intracavernosal pharmacotherapy has resolved most of the controversies
      regarding the aetiology of erectile dysfunction. Impotence is equally divided
      into organic and psychogenic causes. Arterial insufficiency, alcoholism,
      venosinusoidal, neurological and endocrine disorders are known to cause organic
      erectile dysfunction. Two most popular options in the management of erectile
      dysfunction are intracavernosal injections with vasoactive drugs like papavarine,
      phentolamine, and prostaglandin EI with discontinuation rates of 40-50%, and the
      use of external vacuum devices whose limitations include failure to achieve and
      maintain full erection. The use of inflatable penile prostheses is successful but
      limited with periprosthetic infection and cylinder erosion through the skin or
      urethra. Surgical procedures have included revascularisation of penile vessels
      without good results. Surgical ligation of penile veins for venosinusoidal
      incompetence has been successful compared to excision and embolisation which has
      disappointing results. Currently the role of oral medications in the treatment of
      erectile dysfunction is limited. However, there are now several new agents
      including sildenafil, a phosphodiasterase inhibitor, which is undergoing clinical
      trials that appear to be effective.

PMID- 10065172
TI  - Pathogenesis of lupus nephritis: a review.
AB  - Systemic lupus erythematosus (SLE) is a non-organ specific autoimmune disease in
      which the primary autoantigen has been a subject of debate despite detection of
      antibodies to several nuclear antigens. Contrary to previously held belief that
      SLE and, by extension, lupus nephritis is an immune complex disease mediated by
      DNA-AntiDNA complexes, it is becoming increasingly clear that nucleosomes and
      possibly complement factor Clq are the major players in the pathogenesis of these
      entities. This review article looks at the structure, source and possible
      pathogenetic role of nucleosomes and anti-nucleosome specific antibodies in lupus
      nephritis. Additionally, the possible role of Clq and anti-Clq antibodies in the
      pathogenesis of lupus nephritis is considered.

PMID- 10065173
TI  - Health care technology in public health institutions in Kenya.
AB  - OBJECTIVE: To highlight the role of technology in the practice of medicine and
      the delivery of health care in public hospitals, the problems encountered and
      suggested solutions. DESIGN: The article reviews the process of technology
      planning, acquisition, management and assessment. Analysis of results and
      observations leads to recommendation and suggestions. SETTING: Health care
      technology assessment in hospitals in Kenya and South Africa 1998. INSTITUTIONS:
      Twenty four hospitals in Kenya and 54 hospitals in South Africa. RESULTS:
      Technology assessment as a health policy instrument and planning tool has not
      gained recognition in Kenya; acquisition of health care equipment is not done on
      the basis of evidence from relative advantage outcome, cost of ownership or
      returns on investment; tender boards lack the technical expertise to make
      clinical and technical evaluations of health care equipment and; health care is
      compromised due to poor equipment acquisition. CONCLUSION: The planning,
      deployment, management and assessment of technology should be fully integrated
      into health policy and planning. Policy guidelines should include the regulation,
      control and utilisation of health care technologies.

PMID- 10065174
TI  - Computerised tomographic scan of the head in evaluation of stroke in Ghanaians.
AB  - One thousand and three patients clinically diagnosed as stroke cases were
      investigated using computerised tomographic (CT) scan. No diagnosis was made in
      56 (5.58%) of the patients. While 56 cases had the CT scans reported as normal,
      in 40 (4.99%) of the patients disorders other than stroke were diagnosed. They
      included remediable causes like subdural haematoma (ten cases), cerebral abscess
      (eight cases), meningioma (four cases), other brain tumours (eighteen cases).
      Nine hundred and seven of the patients were proven to have suffered a stroke; 547
      (60.3%) were haemorrhagic and 360 (39.7%) were infarctive. These results are at
      variance with previous studies from West Africa which made infarcts the commoner
      stroke type, but reflect those found in Blacks elsewhere in South Africa and
      America. Our results were achieved through the use of the CT scan as opposed to
      the earlier clinically-diagnosed West African studies. The larger number of
      haemorrhagic strokes had therapeutic implications. Trepidation in the use of
      anticoagulants, thrombolytics and fibrinolytics before proof of the pathological
      type is advised. Although clinical evaluation may be more cost-effective in the
      management of stroke, brain imaging techniques are recommended for accuracy in
      diagnosis and appropriate management.

PMID- 10065175
TI  - Clinical profile of Ethiopian patients with breast cancer.
AB  - This prospective study was designed to obtain information on demographic
      characteristics, clinical profile and problems related to early diagnosis and
      treatment of breast cancer in 72 Ethiopian patients. There were 62 females and 10
      males, the female to male ratio being 6.2:1. The age range of the females was 21
      82 (mean 41.8 +/- 12.8) years and that of the males' was 38-75 (mean 52.1 +/-
      12.2) years. The time interval between the onset of breast-related symptoms to
      diagnosis varied from 2-108 (median 12) months. Infiltrating ductal and lobular
      carcinoma histologic types accounted for 85% and 11%, respectively, in 62 cases
      who had surgical biopsies. Surgery was performed in 46 cases out of whom only 21
      cases received adjuvant treatment. Eighteen females refused mastectomy at some
      point before they came to our clinic with metastatic disease. After a median
      follow up duration of 36 (range 2-120) months, 29 cases were alive, 24 died and
      19 were lost to follow up. The cause of death in 17 subjects (71%) was rapidly
      refilling pleural effusion and superimposed infection. Both females and males had
      similar clinical characteristics, except that, the males were older by 10 years.
      Moreover, the females in this series developed breast cancer at a younger age
      (72% were premenopausal) and 76% had advanced disease (Stages III and IV) at
      presentation, similar to females from other African countries. We suggest that
      the attitude of Ethiopian females towards breast cancer has to change through
      continuous but targeted public education.

PMID- 10065176
TI  - Female breast cancer with 'clandestine' lymph node metastases.
AB  - OBJECTIVE: To determine whether or not breast cancer with 'clandestine' lymph
      node metastases differ in any important way from breast cancer with
      macrometastases. METHODS: A study of 116 female breast cancers over a period of
      two years, whose axillary contents were immuno-stained prospectively to detect
      the possible presence of clandestine metastases, that is tumour cells
      identifiable only after monoclonal antibody immunostaining. RESULTS: The
      prevalence of 'clandestine' lymph node metastases was 14.7%. The maximum number
      of 'clandestine' lymph node metastases was three per axilla. In the cases with
      'clandestine' metastases the infiltrating lobular carcinoma (ILC) type was more
      frequently seen than in the node negative cases: (p = 0.038) (RR = 2.44; OR =
      4.0). There was no difference in the hormone receptor status between the cases
      without lymph node metastases and with lymph node metastases, 'clandestine' or
      macrometastases. CONCLUSION: No significant difference was found between breast
      cancers with 'clandestine' or with macrometastases with regard to their clinico
      pathologic features and hormone receptor status. The detection of 'clandestine'
      metastases is a painstaking and time-consuming procedure which, so far, has not
      been shown to be of clinical significance.

PMID- 10065177
TI  - Human plasma derived hepatitis B vaccine: Kenyan experience.
AB  - OBJECTIVE: To determine the efficacy and safety of hepaccine B. DESIGN:
      Vaccination on first-come-first-served basis. SETTING: Kenya Medical Research
      Institute (KEMRI) staff and families at Nairobi, Kenya. PARTICIPANTS: A total of
      107 vaccinees aged 0-10 years and 10 years and above. MAIN OUTCOME: Antibody to
      hepatitis B surface antigen (anti HBs) checked one month after the third dose of
      the vaccine. RESULTS: Ninety seven per cent of the vaccinees developed antiHBs.
      Side effects were few in the form of soreness at site of injection and headache.
      CONCLUSION: Hepaccine B produced good immune response in vaccinees with minimal
      side effects.

PMID- 10065178
TI  - Household survey of access to and utilisation of emergency oral health care
      services in rural Tanzania.
AB  - BACKGROUND: Emergency oral health care, as conceived in Tanzania, is an on demand
      free-of-charge service provided by primary health workers called Rural Medical
      Aides(RMAs). OBJECTIVE: To evaluate accessibility and utilisation of emergency
      oral health care services. DESIGN: Cross-sectional household questionnaire
      survey. SETTING: Rural villages forming a catchment area for rural health centres
      and dispensaries providing emergency oral health care in Rungwe district, Mbeya
      region, Tanzania. SUBJECTS: Two hundred households containing about 1,106
      persons. Half the households were randomly selected from a village where the
      dispensary or health centre was located. The other households were from a village
      distant from the health centre or dispensary. MAIN OUTCOME MEASURES: Self
      reported use of emergency oral health care in a household and perceived barriers
      to the utilisation of this service. RESULTS: More than 90% of the respondents
      knew that emergency oral health care was available at the health centre or
      dispensary. In 40% of the households surveyed, there was a person who had used
      emergency oral health care. Half the respondents perceived that there were some
      barrier in using emergency oral health care. Lack of money to pay for treatment
      or transportation and fear of dental treatment were mentioned as the perceived
      barriers for using emergency oral health care by thirty and seven per cent
      respectively. In a logistic regression model, use of emergency oral health care
      was explained by a positive history of dental problems in the household (OR =
      4.3) and the age of the household informant being more than 40 years (OR = 4.5).
      CONCLUSIONS: The majority in the rural Tanzanian villages surveyed knew about the
      availability of emergency oral health care services. The proportion of households
      which had used these services were relatively high compared to the time span.
      Inability to pay for the services was one of the perceived barriers to their
      utilisation.

PMID- 10065179
TI  - The factor-structure of the Self Reporting Questionnaire (SRQ-20) in South
      Africa.
AB  - This study investigated the factor structure of the Self Reporting Questionnaire
      (SRQ-20) on a sample of 624 standard nine (Grade 11) school pupils selected at
      random from the Northern Province of South Africa. Factor analysis technique was
      used to extract the factors of the SRQ-20. The findings which indicate the
      extraction of four factors; (i) anxiety-depression; (ii) depression; (iii)
      anxiety and; (iv) somatic complaints are discussed in relation to previous
      studies.

PMID- 10065180
TI  - Fine needle aspiration cytology in the management of thyroid enlargement: Ibadan
      experience.
AB  - This report reviews our experience with fine needle aspiration (FNA) cytology in
      the assessment of thyroid enlargement in Ibadan between January 1995 and December
      1997. The diagnostic accuracy of the procedure for malignancy was 80.6% with a
      sensitivity and specificity 83% and 80% respectively in this series. FNAC of
      thyroid enlargement is now a first line investigative procedure for thyroid
      enlargements in the University College Hospital, Ibadan.

PMID- 10065181
TI  - Role of pneumatic otoscopy in the evaluation of tympanic membrane and middle ear
      diseases.
AB  - Many middle ear diseases show visible changes on the tympanic membrane which can
      be identified with pneumatic otoscopy. With practice and patience the technique
      can be easily performed even on infants and very young children and can reveal
      what may guide therapeutic approach. Careful positioning of the patient and
      proper insertion of a fitting ear speculum are of paramount importance. Mobility
      of the tympanic membrane may be absent in certain conditions and decreased or
      increased in other conditions. White masses are sometimes observed in the
      tympanic membrane or in the middle ear. These may be normal bony structures,
      tympanosclerosis or cholesteatoma and pneumatic otoscopy may help differentiate
      these conditions.

PMID- 10065182
TI  - Pattern of occurrence of odontogenic cysts in Nigerians.
AB  - OBJECTIVE: To determine the relative frequency and histopathologic pattern of
      odontogenic cysts in a Nigerian population. DESIGN: Retrospective study of case
      notes and histologic reports and slides. SETTING: Teaching Hospital Ibadan,
      Nigeria. SUBJECTS: Seven hundred and fifteen patients seen between 1982 and 1996
      with histologically confirmed oral lesions. RESULTS: Sixty five (8.8%) of all
      oral lesions during the study period were odontogenic cysts among which 61.9%
      were radicular, 19% dentigerous and 14.3% keratocysts. Other uncharacterised
      odontogenic cysts constituted 3.8%. The peak incidence was in the second decade
      (44.4%) while the mean ages of occurrence were 26.5, 12.8 and 29.3 years for the
      radicular, dentigerous and odontogenic keratocysts respectively. The overall sex
      incidence was almost equal (male to female ratio (1:1.1). The radicular and
      dentigerous cysts were more commonly seen in the maxilla while the odontogenic
      keratocysts were more in the mandible. CONCLUSION: There is need for more studies
      in African populations to establish the true pattern of odontogenic cysts.

PMID- 10065183
TI  - Chronic hepatitis B and neurogenic muscle disease: case report.
AB  - A 17 year-old boy with chronic hepatitis B who developed left-sided muscle
      wasting is reported. When other possible known diseases as the cause of the
      neurogenic muscle disease were excluded it was hypothesised that there was a
      relation between the chronic hepatitis B infection and the neurogenic muscle
      disease. An immunopathogenesis could be explained by the presence of HBsAg in the
      cerebral spinal fluid.

PMID- 10065184
TI  - Duodenal perforation following blunt abdominal trauma: case report.
AB  - A case of severe duodenal injury in a 20-year-old female due to blunt abdominal
      trauma secondary to road traffic accident is presented. The difficulty and hence
      delay in making a diagnosis of duodenal injury is discussed.

PMID- 10065185
TI  - Role of MRI in the diagnosis of cervical brucellar spondylitis: case report.
AB  - Magnetic resonance imaging (MRI) is the most suitable modality for evaluation of
      infectious spondylitis. It is more sensitive than other imaging modalities for
      detecting presence and extent of such infections. Though it is not always
      possible to differentiate various infections on the basis of imaging findings
      alone, there are certain features which along with a good clinical background,
      can differentiate brucellar spondylitis from other spinal infections. It is
      useful to follow up such patients after specific chemotherapy to further confirm
      the diagnosis.

PMID- 10065186
TI  - Airborne surgical outreach services.

PMID- 10065187
TI  - Airborne surgical outreach services in eastern Africa.
AB  - BACKGROUND: African Medical and Research Foundation (AMREF) has for forty years
      offered airborne specialist surgeons or surgical teams to supplement the major
      surgery conducted by local hospital staff, particularly in Kenya and Tanzania.
      OBJECTIVE: To quantify and qualitatively describe the contribution of airborne
      surgical outreach services in relation to the total surgical output of remote
      rural hospitals in Kenya and Tanzania. DATA SOURCES: Surgical theatre
      registration books of one government and two church/mission owned hospitals in
      Kenya and Tanzania from 1994 to 1995; and service records kept by the surgeons
      during outreach trips in the same period. RESULTS: AMREF contributed 15.1% of all
      major operations, and operations performed by AMREF were relatively complex. The
      average number of AMREF's major operations performed per visit was 17 and per
      visit day 4.3. Numerous minor operations and examinations, ward rounds and an
      average of 10 patient consultations per day were done during the visits.
      CONCLUSIONS: Total population-based operation rates, and rates by sex and age,
      are useful indicators for monitoring and comparison. Every hospital should
      report, annually, major operations performed by type and by age and sex of
      patients, with special mention of operations and consultations performed by
      visiting teams, if any. Each hospital should also state the estimated population
      of its current catchment area.

PMID- 10065188
TI  - X-ray diagnosable pneumonia in children with severe malnutrition at Kenyatta
      National Hospital.
AB  - OBJECTIVES: To estimate the prevalence of radiologically evident pneumonia among
      children with severe malnutrition and to evaluate the diagnostic utility of
      commonly used clinical indicators of pneumonia among children with severe
      malnutrition. METHODS: All children with severe malnutrition and admitted at the
      then Paediatric Observation Ward without congestive cardiac failure, severe
      anaemia, or severe dehydration, were clinically evaluated and a posteroanterior
      chest X-ray taken for each child. Pneumonia was diagnosed on the basis of
      radiological changes consistent with pneumonia as reported by an experienced
      radiologist. The performance of the various clinical parameters as diagnostic
      tests for pneumonia were also evaluated. SETTING: Kenyatta National Hospital, a
      tertiary level teaching institution for the University of Nairobi. RESULTS: One
      hundred and seven children comprising 68 males and 39 females were recruited into
      the study. Of these children, 38 had kwashiorkor, 40 had marasmus, while 29 had
      marasmic kwashiorkor. Radiological evidence of pneumonia was found in 58% of
      children with kwashiorkor, 75% with marasmic kwashiorkor, and 82% with marasmus.
      All the commonly used clinical parameters performed poorly as diagnostic tests
      for pneumonia among children with severe malnutrition. CONCLUSION: Prevalence of
      pneumonia was very high among children with severe malnutrition. Available
      clinical parameters, singly or in combination, are poor diagnostic tools for
      pneumonia in children with severe malnutrition. It is advisable to treat children
      with severe malnutrition as if they had pneumonia, even in the absence of
      suggestive clinical signs.

PMID- 10065189
TI  - Isolation of Neisseria gonorrhoeae using urine as a holding medium.
AB  - OBJECTIVE: To utilise urine as a holding medium in isolating Neisseria
      gonorrhoeae in place of urethral, high-vaginal and endocervical swabs. DESIGN:
      Screening and diagnostic test. SETTING: A rural community in Jos and Applied
      Microbiology Research Unit, University of Jos, Jos, Nigeria. SUBJECTS: A random
      sample of 300 asymptomatic individuals (151 males, 149 females). MAIN OUTCOME
      MEASURE: Neisseria gonorrhoeae identification. RESULT: Nineteen Neisseria
      gonorrhoeae isolates were obtained with the isolation rate to 6.3%. Twelve
      isolates from males and seven isolates from females representing 63.7% and 36.8%
      respectively. The peak age group was 21-25 years with 12 positive cases (63.2%).
      CONCLUSION: Urine culture proved an effective and painless alternative in
      screening N. gonorrhoeae in asymptomatic individuals. The age group 21-25 years
      is suggested for intervention studies. This method is less expensive and easily
      accepted by subjects as confidentiality is also maintained.

PMID- 10065190
TI  - Observations on urinary frequency in exclusively breastfed neonates.
AB  - This study was conducted at the University Teaching Hospital, Benin City, Nigeria
      to investigate urinary frequency in exclusively breastfed neonates. Amongst
      exclusively breastfed neonates, 59.0% passed urine eight times or more per day
      while 14.5% passed urine less than five times a day. The comparative figures in
      partially breastfed neonates were 55.8% and 12.8% respectively. There was no
      significant association between the type of breastfeeding and urinary frequency.
      Sex was also not significantly associated with urinary frequency amongst
      exclusively breastfed infants. However, birthweight showed significant
      association with urinary frequency in the analysed sample. It is suggested that
      birthweight, which correlates with gestational maturity may influence urinary
      frequency because of its effect on renal functional maturation and possibly
      differential threshold for intravesical pressures required for initiating the
      micturition reflex. The observed association is, however, not an indication for
      supplementary water in low-birthweight infants since all the infants had normal
      hydration status. It is, therefore, recommended that all neonates should not
      receive supplementary water irrespective of their birthweights.

PMID- 10065191
TI  - Local infiltration and spermatic cord block for inguinal, scrotal and testicular
      surgery.
AB  - This was a prospective study involving 372 male patients. Surgical procedures
      including simple inguinal hernia repair, inguinal lymph node biopsy,
      hydrocelectomy, testicular biopsy, testicular fixation, orchidectomy and scrotal
      exploration were performed under local anaesthesia using various quantities of
      0.5% xylocaine with adrenaline depending on the procedure, in the form of
      spermatic cord block and local infiltration nerve blocks. No premedication was
      given to any patient and only five patients (1.34%) were given intraoperative
      sedation due to anxiety. No complication directly attributed to the anaesthetic
      agent used or the technique of spermatic cord and nerve blocks were reported
      during the study. Three hundred and sixty patients (96.77%) were operated on as
      outpatients and were happy and satisfied to return home on the same day. This
      experience confirms that spermatic cord block accompanied by local infiltration
      with 0.5% xylocaine with adrenaline is simple, safe and effective technique that
      should be used more widely in outpatient urological and general surgical settings
      in this locality. It provides excellent intra-scrotal and inguinal anaesthesia.
      Furthermore, the technique is cost effective, and personnel effective since no
      anaesthetist is required for the procedure which is usually carried out by the
      surgeon. This would enable many more people to afford the surgical procedures.

PMID- 10065192
TI  - Urethral stricture at Ahmadu Bello University Teaching Hospital, Zaria.
AB  - We reviewed 556 male urethral strictures treated at Ahmadu Bello University
      Teaching Hospital, Zaria between 1980 and 1989. Their ages ranged from nine to 80
      years with a mean of 40 +/- 12.9 SD years. Infection caused stricture in 66.5%
      while trauma accounted for 31.7%. Urethral injury associated with pelvic fracture
      from road traffic accident accounted for 68% of the traumatic causes.
      Inflammatory strictures were mainly located in the bulbar urethra (69.9%), while
      most traumatic ones involved membranous urethra (74.4%). Inflammatory strictures
      were mostly multiple (85%) while 90% of traumatic ones were single. Many patients
      with inflammatory strictures had more than one episode of urethritis. About 58%
      of the patients were treated by dilatation, 16% by visual internal urethrotomy
      and 26% by urethroplasty. Best results were obtained in patients treated by
      urethroplasty where 72% were satisfied with their treatment. Overall, 61% of the
      patients were satisfied with their treatment and were voiding urine without
      effort at two years. Re-stricture occurred in 21% and 23% of patients treated by
      urethroplasty and internal urethrotomy respectively. Urethroplasty is advocated
      upon less strict indications where the expertise is available.

PMID- 10065193
TI  - Epidemiological aspects of Fournier's gangrene at Kenyatta National Hospital,
      Nairobi.
AB  - This was a retrospective epidemiological study of 171 patients with scrotal
      (Fournier's gangrene) at Kenyatta National Hospital over eleven year period. The
      age range was 11 days to 90 years with a mean of 35.38 years. This is different
      from other reports of a mean of 40.6 years in the older literature and a mean of
      50 years in the more recent series. The ethnic distribution of Fournier's
      gangrene revealed equal susceptibility among all ethnic groups in this locality.
      Scrotal and genitourinary symptoms were the commonest being present in one
      hundred and two patients (59.7%). The onset of symptoms was insidious in 95
      patients (55.6%), and abrupt in 76 patients (44.4%). Most patients (84.2%)
      presented after more than 48 hours of the onset of symptoms. One hundred and two
      patients (59.65%) presented with localised physical signs compared to sixty nine
      patients (40.35%) who presented with extended lesions. Sources of the lesion were
      known in 82.5% of the patients. Genitourinary sources accounted for 42.1%,
      extragenitourinary 29.2%, and mixed 11.11% among the known causes. Diabetes
      mellitus was the leading major illness associated with Fournier's gangrene,
      presenting in 11 patients (6.42%). Seven other patients (4.09%) had HIV
      infection.

PMID- 10065194
TI  - Oesophageal carcinoma in Tikur Anbessa Hospital, Addis Ababa.
AB  - A five year review of oesophageal carcinoma in Tikur Anbessa Hospital (TAH),
      Department of Surgery, Faculty of Medicine is presented. One hundred and forty
      two patients representing 32.5% of all gastrointestinal and 13.8% of all
      malignant tumours were seen in the Department during the study period. The age
      range was 22 to 88 years with a mean of 54 years. There were 54 females and 88
      males. Dysphagia, weight loss and anaemia were the significant features in the
      majority and 40% of patients presented between four and seven months. Squamous
      cell cancer accounted for 93% of all histologic types. The middle third was the
      commonest site of tumour formation (49%) while the lower third accounted for 44%.
      An operability rate of 56% is recorded but only 24% were suitable for
      oesophagectomy. The post operative mortality was 28%. The commonest causes of
      death were sepsis secondary to anastomotic leak and pneumonia. Follow up was
      possible only for three months for eleven patients and seven months for seven
      patients. The rest could not be traced. It is difficult not to implicate the
      commonly used dietary ingredients in the causation of this tumour.

PMID- 10065195
TI  - Clinical presentation and management of renal cell carcinoma.
AB  - A study of clinical presentation and management of renal cell carcinoma (RCC) in
      35 patients during the period 1983 to 1997 is presented. The peak age was 40-50
      years. Haematuria, abdominal pain, fever of unknown origin and abdominal mass
      were the commonest presenting features. Computerised tomographic (CT) scanning,
      intravenous urography (IVU) and magnetic resonance imaging (MRI) were the
      important diagnostic tools. Early diagnosis and surgery are the most important
      approaches in management.

PMID- 10065196
TI  - Effects of the extract of Spirostachys venenifera Pax on the immune response in
      mice.
AB  - The effects of the methanol extract of Spirostachys venenifera Pax (SVP) on the
      immune response in mice was investigated. Keyhole limpet haemocyanin (KLH) was
      the antigen. An enzyme linked immunosorbent assay (ELISA) was used to monitor
      serum antibody levels in mice exposed to various doses of SVP at a dosage of 0.1
      mg/Kg. In mice in vivo, SVP caused a significant suppression of the immune
      response compared to control mice that received no SVP. A haemolytic plaque assay
      was used to monitor the effect of SVP on antibody producing B lymphocytes from
      the peritoneum and from the spleen in vitro. SVP caused a reduction in the number
      of plaque forming cells (PFC) at 0.1 ug/ml with peritoneal B cells. There was
      further reduction of PFC with higher doses of SVP. With the spleen B cells, clear
      reduction in PFC was seen only with the higher doses of SVP, from 1 ug/ml upwards
      to 100 ug/ml. The prospect of developing a new immunosuppressive agent from SVP
      is a welcome possibility that can add to the newer immunosuppressive agents with
      greater efficacy and less side effects in comparison to the traditional ones.

PMID- 10065197
TI  - Effect of propylthiouracil induced hypothyroidism in developing rat cerebellum:
      comparison of cerebellar parameters in five day old normal and treated rat pups.
AB  - The effect of pre and postnatal hypothyroid environment on the development of
      cerebellum in the rat pups was determined. Four groups of rat dams, namely
      control, Group I, II and III were treated with propylthiouracil (PTU) in water
      for different length of time during pregnancy and nursing periods. The pups born
      from these dam groups were subsequently named after the corresponding dam group,
      namely control, Group I, II and III. General quantitative results showed that
      pups from the treated dams had significantly lower (p < 0.05) body weights
      compared to control pups. Cerebella from five day old pups were taken and
      structural changes estimated using unbiased "design based" stereological methods,
      which have made it possible to investigate specific qualities in the organ. The
      total volumes of cerebellum and intracerebellar nuclei were estimated using
      Cavalieri Principle. The mean total volume of cerebellum and the mean total
      volume of intracerebellar nuclei were significantly lower (p < 0.05) in all the
      pup groups (I, II, III) from the treated dams compared to control pups from the
      control dams. The cerebellar volume decreased in relation to the duration of
      treatment. The mean ratio of the total volume of intracerebellar nuclei to volume
      of cerebellum was significantly increased (p < 0.05) in Group III pups compared
      to control and Group I pups. The mean numerical density of neurones in the
      intracerebellar nuclei was nearly equal in all the pup groups except in Group III
      pups whereby it was increased. The mean total number of neurones in Groups I and
      II pups was reduced, but did not reach statistical significance. The mean
      numerical density of neuroglia in the intracerebellar nuclei was nearly the same
      in all the pup groups, the mean total number of glial cells was significantly
      reduced (p < 0.05) in Groups I and II pups compared to control and the mean
      neuron/glial ratio was increased in Group III pups compared to control and other
      treated groups. Thus, the neuroglia appear to be more sensitive to hypothyroidism
      than neurons. The above results show that PTU-induced hypothyroidism causes
      reduction in structural parameters in developing cerebellum and confirm that
      growth and maturation of the foetal cerebellum is dependent on the maintenance of
      normal T4 and T3 levels in the pregnant dam and developing pups during pre and
      postnatal stages of development.

PMID- 10065198
TI  - Treatment options in lupus nephritis.
AB  - Like systemic lupus erythematosus (SLE) itself, manifestations of lupus nephritis
      are highly varied in their clinical presentation, ranging from mild proteinuria
      to rapidly progressive glomerulonephritis causing renal insufficiency within
      weeks. The clinical variability is in keeping with the broad spectrum of
      histological abnormalities present in renal biopsy specimens from these patients.
      The therapeutic modalities currently being used in lupus nephritis include oral
      steroids, pulse methylprednisolone and cytotoxic drugs such as cyclophosphamide
      and azathioprine either singly or in combinations, depending on the World Health
      Organisation morphologic classification of the disease. The use of plasmapheresis
      for proliferative lupus nephritis (WHO class III and IV) and cyclosporin for
      membranous lupus nephritis (WHO class V) is based on open trials, but not
      supported by randomised controlled trials. This review assesses the therapeutic
      modalities available for the treatment of lupus nephritis, giving the available
      evidence from the literature and acknowledging that none of them might be
      perfect.

PMID- 10065199
TI  - Congenital diaphragmatic hernia: report of three cases.
AB  - Three cases of congenital diaphragmatic hernia (CHD) are presented with special
      emphasis on a neonate with an unusual combination of abnormalities. It was noted
      that in all three the hernias were of the Bochdaleck's type. CDH may not always
      be a single isolated failure of closure of the pleural peritoneal hiatus but a
      more complex multi organ anomaly.

PMID- 10065200
TI  - Polycystic kidney disease in tuberous sclerosis complex: case report.
AB  - Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder
      characterised by seizures, mental retardation, cutaneous lesions and visceral
      harmatoma. We describe a 4 1/2-year old boy in whom in addition to the commonly
      described features of TSC, adult-type polycystic kidneys, a scantily reported
      occurrence, was an associated feature.

PMID- 10065201
TI  - Lupus anticoagulant syndrome: case report.
AB  - A twenty seven year old female was referred to our department with deep vein
      thrombosis, abnormal activated partial thromboplastin time (aPTT) ratio 1:60 and
      prothrombin time (PT) INR of 3:11. She had history of loss of pregnancies
      previously. Coagulation tests with pooled normal fresh plasma did not correct a
      PTT because of a coagulation inhibitor and only partially corrected PT. Kaolin
      clotting time (KCT) of patient plasma (PP) and a mixture of PP/normal plasma (NP)
      detected the lupus anticoagulant (LA). Venereal Disease Laboratory (VDRL) test on
      the patient's serum was positive with low titre 1:8 while Treponema Pallidum
      haemaglutination test (TPHA) was negative. Anticardiolipin antibodies IgG were
      raised while IgM levels were within normal levels. This was a case of lupus
      anticoagulant syndrome. The patient was treated with unfractionated heparin and
      warfarin and later started on salicylates and prednisone.

PMID- 10065202
TI  - Patient follow up care after open heart surgery.

PMID- 10065203
TI  - Follow up of patients after open heart surgery.
AB  - OBJECTIVE: To determine the patient drop out to postoperative follow up for heart
      patients at the Kenyatta National Hospital. DESIGN SETTING AND PARTICIPANTS: The
      study analysed the postoperative attendance of heart patients to the surgical
      outpatient clinic at the KNH. Data on clinic attendance was collected over a one
      year period from patient files and from clinic attendance. RESULTS: A total of
      four hundred and seventy-five open heart operations have been performed at the
      Kenyatta National Hospital over the last twenty-five years. The patients' mean
      age is 18.0 years. Clinic follow up rate over this period is 85% at one-year, 62%
      at five-years, 32% at ten-years and 13% at fifteen-years. A number of patients
      who had since fallen out to clinic follow up were traced during the study period,
      when included into the analysis the revised figures are 85%, 70%, 40% and 24%
      respectively. The difference is statistically significant (p = 0.019). There was
      no significant statistical difference in the follow up between males and females
      (p = 0.278), however between patients operated for congenital heart diseases
      compared to valve patients, the difference was significant (p = 0.007), valve
      patients having a better follow up. The five-year follow up for isolated mitral,
      aortic and double valve replacements were 94%, 74% and 78% respectively.
      CONCLUSION: Despite deceptively good follow up figures, our figures are in fact
      poor when age is considered. Financial combined with logistical problems are the
      most likely causes of poor follow up.

PMID- 10065204
TI  - Perception of risk, sexual behaviour and STD/HIV prevalence in western Kenya.
AB  - OBJECTIVE: To determine the feasibility and acceptability of collecting data on
      sexual practices, knowledge, attitudes and perception of risk with regard to HIV
      and STD infection in two clinic populations. DESIGN: A cross sectional survey
      carried out between June and July 1992. SETTING: An urban and a rural health
      centre in western Kenya. SUBJECTS: One hundred and sixty women attending Maternal
      Child Health (MCH) and Family Planning Clinics (FP). INTERVENTIONS: Screening
      STDs including N. gonorrhoea, C. trachomatis, T. vaginalis and syphilis. In
      addition subjects were interviewed about sexual practices, knowledge, attitudes
      and perception of risk with regard to HIV and STD infection. RESULTS: The
      presence of any STD including HIV was detected in 36.2% of women at the urban
      clinic and 21.2% of women at the rural clinic. The demographics of the two
      populations were similar with respect to age but were significantly different for
      several variables including marital status, ethnicity and education. Knowledge of
      STDs and HIV was nearly universal in both clinic populations with > 96% of
      patients being aware of the existence of such diseases. 76.3% of women at the
      urban clinic felt they could get an STD as compared to 48.8% at the rural clinic
      (p < 0.02). This awareness of vulnerability among the urban population was also
      seen for HIV. CONCLUSION: It appears to be feasible to conduct studies of sexual
      practices and perceptions of risk for STD/HIV acquisition in women attending
      health centres in Kenya.

PMID- 10065205
TI  - Situation analysis of HIV/AIDS epidemic in sub-Saharan Africa.
AB  - At the end of 1997 about twenty one million persons were living with HIV/AIDS in
      sub-Saharan Africa, representing almost two third of the world's total. Three
      broadly defined areas, which include countries with severe epidemics and others
      with epidemics at their intermediate stage, account for almost 90% of all current
      HIV infections in tropical Africa. According to World Health Organization (WHO),
      the current data show very high increases in HIV/AIDS incidence as well as
      serious underreporting of the disease in the last five years. Sub-Saharan Africa
      has been particularly hard hit by the disease because of a combination of poor
      social and health education and also because of other endemic sexually
      transmitted diseases which significantly increase the chance of HIV transmission.

PMID- 10065206
TI  - Community perceptions and treatment seeking for malaria in Baringo district,
      Kenya: implications for disease control.
AB  - BACKGROUND: Malaria is one of the leading causes of morbidity and mortality in
      Kenya. Its control depends on many factors, some of which have not been studied
      at the level of rural community. OBJECTIVE: To identify what households in a
      Kenyan rural community perceive to be the cause and symptoms of malaria and their
      treatment behaviour for malaria. SETTING: Community-based study conducted in
      Marigat division of Baringo district. DESIGN: Cross-sectional study utilising
      qualitative ethnographic and semi-quantitative methods. Multi-stage cluster
      stratified procedure was used to select the villages, after which screening
      interviews were used to identify households. Finally, interviews and informal
      discussions were conducted with 463 heads of households with self-reported cases
      of malaria. The study was conducted between April and October 1992. RESULTS: The
      study findings indicate that the community has multiple aetiologies for malaria.
      Of the 463 heads of households interviewed, 258 (58.5%) associated the cause of
      the disease to the mosquito. Other aetiological beliefs included: wild vegetables
      (13.1%), water (11%) and milk (9.8%). Many of the respondents (90%) could
      identify malaria by several correct symptoms. In the treatment of malaria,
      various health resources such as public health facilities, over-the counter
      medications, private clinics and herbal medicines are used. For first choice of
      care, many households used public health facilities. However, if the malaria
      illness persisted, other forms of treatment especially private clinics and
      medicinal plants seem to have been preferred. CONCLUSION: Understanding community
      perceptions of aetiology, symptom identification and treatment of malaria is an
      important step towards the control of the disease.

PMID- 10065207
TI  - Quality of oral and parenteral chloroquine in Kampala.
AB  - Malaria remains an important public health problem in Uganda. The mainstay of
      treatment is still chloroquine. However, recently there have been several reports
      of poor response to chloroquine treatment. We do not know whether the reported
      poor response is due to true resistance or poor quality of the drug in the
      market. This study was done to assess the quality of chloroquine dosage forms in
      Kampala. The study was cross-sectional; end-point designed to assess the amount
      of the active ingredient in the tablet and injection dosage forms of the drug.
      The quality assay was based on the BP, 1988 standard, using both visual and
      potentiometric analysis technique. The study demonstrated that there is a problem
      with the quality of chloroquine in the market. Upto 30% of the tablet samples and
      33% of injection samples contained less than the stated amount of the active
      ingredient. This may be one of the reasons for the reported poor response of
      malaria to chloroquine treatment in Uganda. Given that routine laboratory testing
      of active ingredients in pharmaceuticals is not practised in Uganda, this study
      has demonstrated the necessity for establishment of a drug quality control
      laboratory in the country.

PMID- 10065208
TI  - Prevalence and severity of symptoms of asthma, allergic rhino-conjunctivitis and
      atopic eczema in secondary school children in Ibadan, Nigeria.
AB  - This study was part of the effort of the International Study of Asthma and
      Allergies in Childhood (ISAAC) Steering Committee to evaluate the epidemiology of
      asthma and allergic diseases around the world. Three thousand and fifty eight
      randomly selected children aged 13-14 years were studied, using a standard
      questionnaire developed and field tested by the ISAAC Steering Committee, to
      establish the prevalence and severity of symptoms of asthma, allergic
      rhinoconjunctivitis and atopic eczema. Of the 3,058 children, there were 1,659
      (54.3%) females and 1,399 (45.7%) males (F:M ratio 1.2:1). The cumulative
      prevalence rates of wheezing, rhinitis other than common cold, and symptoms of
      eczema were 16.4%, 54.1% and 26.1%, respectively while within the immediate 12
      month period, the rates were 10.7%, 45.2% and 22.4%, respectively. However,
      rhinitis associated with itchy eyes (allergic rhinoconjunctivitis) was reported
      by 39.2% of the school children. The prevalence of doctor-diagnosed asthma was
      18.4%. Multiple logistic regression analysis showed that a higher prevalence of
      wheezing and rhinitis was associated with itchy eyes. The prevalence of severe
      symptoms of asthma, allergic rhinitis and eczema were higher when compared with a
      similar study in Kenya. However, the prevalence of symptoms of asthma was lower
      and that of allergic rhinoconjunctivitis higher in our series. There is a need
      for further studies to investigate the risk factors which might be responsible
      for the apparently different patterns in these two African countries.

PMID- 10065209
TI  - Toxin production and antimicrobial resistance of Escherichia coli river water
      isolates.
AB  - OBJECTIVES: To establish the types of E. coli isolates that are found in river
      water around Nairobi and to assess the potential risk of use of this water to
      human health. DESIGN: Multiple stratified sampling was carried out. Surface
      sampling was used in the entire study. SETTING: The study was carried out on
      river waters surrounding Nairobi, Kenya. SUBJECTS: Forty Escherichia coli strains
      isolated from river water. MAIN OUTCOME MEASURES: Serotyping, toxin gene tests
      and susceptibility to tetracyclines, ampicillin, chloramphenicol and kanamycin
      were analysed. RESULTS: None of the isolates could be specifically serotyped
      using the available antisera. Toxin gene production tests using the colony
      hybridisation technique revealed that nine (22.5%) of the strains were positive
      for heat stable (ST) toxin, seven (17.5%) to the heat labile (LT) toxin and two
      (5%) to both. Using the Agar Disk Diffusion technique, eighty per cent of the
      strains were susceptible to all four antibiotics, while twenty per cent of the
      strains showed multiple resistance. None of the strains was resistant to all four
      antibiotics while no strain showed resistance to kanamycin. CONCLUSION: None of
      the E. coli isolates was serotypable and it was therefore not possible to
      determine whether serologically identical strains of ETEC were haboured by man or
      animals. Toxin gene tests results showed that there is some risk of infection by
      diarrhoea causing ETEC to man and animals. Toxin gene tests results showed that
      there is some risk of infection by diarrhoea causing ETEC to man and animals if
      they consume this water untreated and there is evidence to show resistance of
      bacteria to antibiotics, hence appropriate health measures should be adhered to.

PMID- 10065210
TI  - Antimicrobial prophylactic practice in surgical patients.
AB  - OBJECTIVE: To evaluate the prescribing patterns of surgeons for pre-operative
      antimicrobial prophylaxis. DESIGN: A retrospective study based on data obtained
      from case records of surgical patients admitted into the Department of Surgery.
      SETTING: Department of Surgery, Royal Commission Medical Center, Madinat Yambu Al
      Sinayah. SUBJECTS: The study population comprised of 888 surgical patients who
      received antibiotic therapy either for prophylaxis or treatment during the period
      1st November 1992 and 28th February 1995. RESULTS: A total of 888 surgical
      patients received antibiotics during the study period, 191 (21.5%) for
      prophylaxis while 697 (78.5%) were given antibiotics for therapy before and after
      surgery. Ceftriaxone was the most commonly used antibiotic for prophylaxis,
      followed by augmentin and cefotaxime, and these were frequently given in multiple
      doses, extending beyond 24 hours. CONCLUSION: There was unwarranted and over use
      of prophylactic agents in at least 70% of the patients, with increased costs to
      the Hospital. Effective prophylaxis can be accomplished with a single dose of a
      cephalosporin, such as ceftriaxone, cefuroxime or cefazolin, for the common
      surgical procedures. It is recommended that better compliance with principles of
      surgical antimicrobial prophylaxis be implemented Prophylactic antibiotic audit
      measures should be carried out by the control committee. The development of
      guidelines and standing orders for antimicrobial prophylaxis should help to
      improve compliance.

PMID- 10065211
TI  - Alcohol-related road traffic injuries in Eldoret, Kenya.
AB  - OBJECTIVE: To establish the extent of alcohol involvement in motor vehicle
      crashes occurring in Eldoret in western Kenya. DESIGN: A descriptive hospital
      based study. SETTING AND SUBJECTS: Crash-involved patients aged 16 years and
      above presenting for treatment in all hospitals located in Eldoret town over a
      period of six months. METHODS: Casualties were enrolled consecutively. A
      questionnaire eliciting demographics and crash circumstances was administered.
      Blood alcohol concentration (BAC) was evaluated either by breath tests or venous
      blood sample analysis in consenting casualties presenting within 10 hours of the
      crash. BAC levels of 5 mg% and greater were taken as a positive test; patients
      registering BAC levels equal to or greater than 50 mg% were considered as being
      intoxicated. RESULTS: Of the 188 patients evaluated, 23.4% were BAC positive and
      12.2% were intoxicated. Males were twice as likely as females to have been
      drinking prior to the crash (26.4% versus 13.6%; p = 0.08). Significantly greater
      proportions of night-time and weekend crashes involved intoxicated subjects (p =
      0.02 and p = 0.03, respectively). Motor vehicle drives were the most affected by
      alcohol (60%), whereas pedestrians (33.3%), passengers (16%) and pedal cyclists
      (8.3%) were involved to a lesser extent. In comparison to passengers, drivers
      were eight times more likely to have been drinking (OR = 7.9, p = 0.04).
      CONCLUSIONS: Alcohol is a contributing factor in a substantial proportion of
      traffic crashes occurring in western Kenya. Policy response and specific
      interventions for discouraging driving under the influence of alcohol, including
      the establishment and enforcement of a legal BAC limit are needed.

PMID- 10065212
TI  - Periodontal status and oral hygiene practices of pregnant and non-pregnant women.
AB  - One hundred pregnant and another hundred non-pregnant women aged between 16-45
      years attending the outpatient clinic of the department of Obstetrics and
      Gynaecology of Korle-Bu Teaching Hospital were examined and their periodontal
      status assessed using the Community Periodontal Index for Treatment Needs
      (CPITN). Selection was by convenient sampling. Only second and third trimester
      pregnant women were included in the study. Results were recorded using World
      Health Organization (WHO) standard oral health assessment form and analysed using
      SPSS for Windows. Overall there was a higher incidence of gingival bleeding or
      worse score among the pregnant (89%) than the non-pregnant women (61%). This was
      the case in each of the three age groups considered. Among the non-pregnant women
      the mean number of sextants with healthy gingivae was above 3.5 in all age groups
      with an average of 3.78. The mean for second trimester pregnant women was 1.55
      and third trimester 2.73. The mean number sextants with bleeding gingivae was
      0.698 among the non-pregnant women, whilst that for second trimester and third
      trimester women were 3.20 and 1.96 respectively. The commonest method of oral
      hygiene among both the pregnant and non-pregnant women was a combination of the
      use of chewing stick and toothbrush with paste. The second commonest method was
      chewing stick alone among the pregnant women and among the non-pregnant women
      toothbrushing with paste. The mean number of sextants with gingival bleeding
      among the second trimester pregnant women was consistently high (> 3)
      irrespective of the method of oral hygiene used. The level of gingival bleeding
      during pregnancy is not significantly affected by any of the methods of oral
      hygiene used (p < 0.05) which is higher during the second trimester compared with
      the third trimester of pregnancy.

PMID- 10065213
TI  - The plantar reflex in young healthy adults.
AB  - The plantar reflex was empirically observed to be relatively absent in Africans
      about three decades ago. It was hypothesised that barefoot walking that was the
      custom of the patients studied at the time, might have made the soles of the feet
      insensitive to stimulation. In a sample of 193 young adults who do not walk
      barefoot and had no clinical evidence of hyperkeratosis or callosities on the
      soles, the plantar reflex was absent in 27%. This finding suggests that the
      absence of the reflex is not necessarily consequent on previous trauma to the
      soles in an African community. Lack of comparative data showing the pattern of
      the plantar reflex in different communities makes it difficult to judge whether
      the frequency found in this study is usual, high or relatively low.

PMID- 10065214
TI  - Colorectal neoplasms: a retrospective study.
AB  - A total of 254 cases of colorectal neoplasms were studied. A male predominance
      was noted with both benign and malignant neoplasms (M:F of 4.6:1 and 1.1:1
      respectively). The peak incidence was in the fifth decade. The rectum was the
      commonest site for both benign and malignant neoplasms (75% and 63% respectively)
      followed by the sigmoid colon (11% and 16% respectively). Right-sided cancers
      presented commonly as fungating masses (74%) while left sided cancers were
      predominantly of the ulcerating/infiltrating pattern (81%). The commonest benign
      neoplasm was tubular adenoma (39%) while the commonest malignant neoplasm was
      adenocarcinoma (90%) followed by squamous cell carcinoma (4%). Advanced stage on
      presentation was noted with these cancers, especially the mucinous adenocarcinoma
      variant. This may be explained by the usual late presentation of patients to
      orthodox doctors in our environment.

PMID- 10065215
TI  - Diagnosis of disseminated alveolar rhabdomyosarcoma using cytogenetics: case
      report.
AB  - The clinical, histologic and cytogenetic features of a patient with the alveolar
      subtype of rhabdomyosarcoma (RMS) were investigated. The patient presented with a
      widely disseminated tumour including bone marrow involvement, and was a
      diagnostic dilemma. The presence of translocation (2;13)(q37;q14), which is
      strongly associated with alveolar RMS helped make the diagnosis. A review of
      other published cases confirms the strong association of (2;13) with alveolar
      RMS. The importance of considering RMS as a differential diagnosis in patients
      presenting with disseminated tumour as the only finding is stressed. This case
      also shows how cytogenetic investigation of similar patients may provide a
      diagnosis.

PMID- 10065216
TI  - Retrorectal cystic harmatoma (tailgut cyst) in an infant: case report.
AB  - We report the case of a day old infant who presented with a large cystic swelling
      in the sacroccoygeal area distorting the gluteal folds and displacing the anus
      anteriorly. Rectal examination revealed less than twenty five per cent of the
      lesion in retrorectal space, plain x-rays did not show any calcification. The
      infant had excision surgery at seven days of age and did well thereafter.
      Although most TGC cases were reported in adults the present case fulfills the
      anatomical and histological criteria for diagnosis, and it may be the first such
      case in a child less than one month old.

PMID- 10065217
TI  - Thyroid gland papillary carcinoma with fibromatosis-like stroma: case report.
AB  - Papillary carcinoma of the thyroid may show a variable degree of fibrosis of the
      stroma, but proliferation of the stromal fibroblasts mimicking fibromatosis is
      rare. There appears to be a new variant of papillary carcinoma of the thyroid
      associated with exuberant proliferation of the fibroblasts resembling
      fibromatosis. We present one such case in a 50 year old woman and succinctly
      reviewed the relevant literature of this rare variant. The necessity of a
      diligent search for a papillary carcinoma in thyroid gland which shows a
      proliferative fibrous lesion is stressed.

PMID- 10065218
TI  - Effects of tobacco smoking on the African continent: analysis of lung cancer
      incidence rates from population based cancer registries.

PMID- 10065219
TI  - [Pertussis in young infants].
AB  - Four infants, three girls aged 4 weeks, 2.5 months and 3 months, and a boy aged 2
      months, were hospitalized because of severe respiratory distress. Apnoea spells
      with bradycardia and hypoxia were seen in two of the patients, one showing
      convulsions as well, and bronchopneumonia in the other two, of whom one
      eventually died. All suffered from pertussis. During outbreaks of pertussis,
      infants less than 6 months of age are at highest risk for severe disease. In this
      age group, however, the clinical signs of pertussis are often atypical. Classical
      symptoms such as paroxysms of cough and loud whoops may be absent while feeding
      problems, apnoea, cyanosis and bradycardia may be present. For infants younger
      than 6 months with signs indicating pertussis hospitalization is indicated. In
      the current vaccination schedule in the Netherlands infants are vaccinated at 3,
      4, 5 and 11 months of age. Starting in 1999 the first vaccination will be
      administered at the age of 2 months.

PMID- 10065220
TI  - [Bronchoalveolar lavage in the diagnosis of diffuse interstitial lung disease].
AB  - Since the introduction of bronchoalveolar lavage (BAL), this technique is used
      both clinically and for research. Use of BAL as a diagnostic aid was introduced
      fairly recently. For the different steps of the procedure a standardized approach
      has been proposed. Analysis of BAL fluid includes determination of the total
      number of cells, of the differentiation and of non-cellular components, as well
      as various staining and culturing methods. The analysis may be useful in the
      diagnosis of interstitial pulmonary diseases and opportunistic infections.
      Smoking and pharmacotherapy affect the results of the analysis. BAL is a safe
      procedure with hardly any side effects. This method may in some diseases replace
      more invasive diagnostic procedures such as biopsy by demonstrating
      characteristic cells or micro-organisms.

PMID- 10065221
TI  - [Obstructive sleep apnea syndrome in children].
AB  - The obstructive sleep apnoea syndrome (OSAS) in children is a clinical syndrome
      resulting from complete or partial obstruction of the upper respiratory tract
      during sleep. The pathogenesis is multifactorial; clear risk groups are children
      with anatomical anomalies of the upper airways, neurological abnormalities and
      genetic syndromes (including craniofacial syndromes). The clinical symptoms of
      OSAS in children vary. In partial obstructions, the most frequent forms, the
      patients may snore and have impaired respiration during sleep. Polysomnography
      contributes to definite confirmation and specification of the clinical diagnosis.
      Standard values should be interpreted with respect to age. Adenotonsillectomy is
      the most frequent treatment of children with OSAS. In persistent symptoms,
      continuous positive pressure therapy is often successful. The natural evolution
      and the long-term prognosis of OSAS in children are still unknown.

PMID- 10065222
TI  - [Benign paroxysmal positional vertigo].
AB  - Benign paroxysmal positional vertigo is a common malfunction of the labyrinth,
      most frequently of the posterior canal, due to clot of debris in the endolymph.
      The attacks of vertigo are characterised by dependency on position, latency after
      positioning of the head, short duration, nystagmus, reversibility and
      fatiguableness. The diagnosis can be based on history, physical examination and
      provocative tilting of the head as described by Dix and Hallpike. In a typical
      case further investigations are not necessary. The symptoms often improve
      spontaneously. Half of the patients can be cured directly by stepwise tilting.
      This probably removes the clot from the canal of the labyrinth to the utriculus.
      Specific positional exercises also often have a good result, but not as quickly.
      Drug therapy has no place in the treatment.

PMID- 10065223
TI  - [The Dutch version of 'Functional Status II(R)': a questionnaire measuring the
      functional health status of children].
AB  - OBJECTIVE: Clinimetric evaluation of the Dutch version of the Functional Status
      II(R) (FS II), measuring children's behaviour and the effect of disease on it.
      DESIGN: Descriptive. SETTING: University of Utrecht, department of General
      Practice Medicine, and Julius Centre for Patient-linked Research. METHODS:
      Parents of children (6 months-11 years of age) with or without asthma were
      questioned using the Dutch translation of the FS II. Parents of children with
      asthma and of control children were questioned again using the FS II after 24
      hours and after one month. A child version of the FS II, developed by our group,
      was used for children between 8 and 12 years of age. We tested internal
      consistency, test-retest reliability, discriminant validity, sensitivity to
      parents' opinion on presence or absence of health complaints and agreement
      between the parent and the child version. RESULTS: The group included 124 parents
      of asthmatic children and 224 parents of control children, 111 of whom were aged
      8-12 years. The parent version of the FS II showed good reliability and validity.
      Cronbach's alpha, measuring internal consistency, was between 0.66 and 0.90, and
      the 24-hour test-retest reliability was between 0.83 and 0.92. FS II-scores of
      children with asthma were significantly lower than those of children in the
      control group, and scores of children with health complaints were significantly
      lower than those of children without any health complaints, cross-sectionally as
      well as longitudinally. Reliability and validity figures of the child version of
      the FS II were far behind those of the parent version. Scores on the child
      version were only weakly related to those on the parent version. CONCLUSION: The
      parent version of the Dutch FS II is recommended as a generic measure of
      functional health status of children for medical research. The child version
      should be improved first.

PMID- 10065224
TI  - [The Dutch 'Rand General Health Rating Index for Children': a questionnaire
      measuring the general health status of children].
AB  - OBJECTIVE: Clinimetric evaluation of the Dutch version of the RAND general health
      rating index for children (child RAND), measuring the general health of children.
      DESIGN: Descriptive. METHOD: The child RAND, containing 7 questions, was
      administered to parents of 124 children with asthma and of an unselected control
      group of 224 children, all between 6 months and 12 years of age. The parents also
      answered a question about the existence of complaints about health. Measurements
      were repeated after 24 hours and after one month. We tested internal consistency,
      test-retest reliability, discriminant validity and sensitivity to change. Results
      were compared with those of the Functional status II (FS II). RESULTS: The child
      RAND showed good reliability and validity. Cronbach's alpha was between 0.87 and
      0.88 in the asthma group and between 0.71 and 0.80 in the control group. Test
      retest reliability was 0.93 in the asthma group and 0.83 in the control group.
      Scores on the child RAND of children with asthma were significantly lower than
      those of children in the control group, and scores of children with health
      complaints were significantly lower than those of children without any health
      complaints in both groups. The sensitivity to change was lower than that of the
      FS II. The figures of the child RAND on the other measures of reliability and
      validity were comparable with those of the FS II. CONCLUSION: The Dutch child
      RAND is recommended as a generic measure of perceived health of children for
      medical research and may serve as a valuable addition to the measurement of
      functional health status by the FS II.

PMID- 10065225
TI  - [Pilomatrixoma often not identified as such].
AB  - OBJECTIVE: To inventory incidence, diagnosis and treatment of pilomatrixoma.
      DESIGN: Retrospective. METHOD: Patients treated in the period 1984-1996 in the
      department of Surgery of the Medical Spectrum Twente, Enschede for a
      pilomatrixoma were traced via the Dutch Automatic Morbid-Anatomical Records
      Office (PALGA). Data were collected by status study. Also, the patients or their
      parents were interviewed by telephone about recurrences. RESULTS: Forty-eight
      patients with 54 pilomatrixomas had been treated. The ages varied from 2 to 77
      years, 14 patients were younger than 14 years. The correct diagnosis had been
      made preoperatively in 11 patients (20%) in four of whom (7%) the manifestation
      was not the first one. In many cases (69%), the condition was mistaken for an
      atheromatous cyst, in children as well (in 47% of the cases). The pilomatrixoma
      was localized in the head and neck area 25 times, in eight of these in the
      parotid region. Owing to incorrect interpretation of the abnormality, three
      children with a pilomatrixoma in the head and neck area underwent a more radical
      operation than necessary. CONCLUSION: The clinical diagnosis was frequently
      missed. In cutaneous tumours occurring in children or localized in the head and
      neck area the diagnosis of pilomatrixoma should be considered.

PMID- 10065227
TI  - [Hearing impairment].

PMID- 10065226
TI  - [Open lung biopsy in severely ill patients with unrecognized pulmonary
      infiltrates].
AB  - In three patients, a man aged 34 with aids, a woman aged 67 with recurrent major
      dyspnoea and a woman aged 73 with chronic lymphatic leukaemia, examination
      revealed progressive dyspnoea while the chest X-rays showed infiltrative lesions
      in both lungs. In view of the inadequate response to the treatment administered,
      an open lung biopsy was performed, following which the diagnosis could be made.
      Adequate treatment was then started and followed by clinical recovery. It is not
      clear if open lung biopsy carries higher risks of mortality and morbidity than
      biopsy by means of flexible bronchoscopy. Open lung biopsy more often leads to a
      classifying diagnosis. For collection of endobronchial or transbronchial biopsy
      samples in ununderstood diffuse interstitial lung diseases, flexible bronchoscopy
      is the method of first choice. Open lung biopsy is a justified supplementary
      examination, at any rate in severely ill, immunocompromised patients who require
      adequate therapy without delay.

PMID- 10065228
TI  - [Hearing impairment].

PMID- 10065229
TI  - [Recent disciplinary committee rulings foster defensive medicine].

PMID- 10065230
TI  - [Frontotemporal dementia in a young woman with apparent schizophrenia].

PMID- 10065231
TI  - [A patient with tetanus without an obvious point of entry].

PMID- 10065232
TI  - [Dental implants: a better anchor for dentures].
AB  - Loss of teeth results in resorption of the jaws. As a consequence the denture
      bearing area progressively reduces, eventually causing loss of retention and
      stability of the conventional denture. In three patients, two women aged 36 and
      37 and a man aged 46, suffering from severe problems with their conventional
      dentures endosteal implants were inserted in the jawbone. After the healing
      period the dentist fabricated an implant-retained overdenture. The patients were
      very satisfied with the final result. Endosteal implants are, especially in the
      mandible, a reliable treatment modality for a stable implant-retained denture in
      case of patients suffering from retention problems with their conventional
      dentures.

PMID- 10065233
TI  - [Is the difference between the educational requirements and the final standards
      of medical studies a problem?].
AB  - Last year a ministerial order was issued concerning the requirements of the study
      of medicine, stating the general end terms and listing health problems as a
      starting point for this study. The end terms have been made less specific than
      they were in the first draft, to achieve compatibility between existing European
      guidelines and Dutch education legislation. The list of problems is not in
      keeping with this, however. Furthermore, problem-oriented education that meets
      the end terms requires information about the age and sex-specific distribution of
      diseases. Owing to the continuous morbidity registration by general
      practitioners, part of this information is already present and more is expected
      to become available.

PMID- 10065234
TI  - [Risks of silicone breast implants unproven].
AB  - The moratorium in the USA on inserting breast implants filled with silicone gel
      caused global alarm by inaccurate media reports resulting from settlements and
      verdicts against the manufacturers. In fact, there still is no scientific
      evidence that the implants have negative effects on health. On the contrary,
      there is an increasing number of studies that were unable to prove a link between
      the implants and diseases, specifically cancer, autoimmune disease or connective
      tissue disease. The European organization of plastic surgeons again stressed this
      point in June 1998. In the Netherlands it has been obligatory since June 1998 for
      all medical implants to carry a quality mark. In addition, it is the intention
      that data on silicone breast implants will be recorded in a national
      registration.

PMID- 10065235
TI  - [Vertical HIV-I-transmission. I. Risk and prevention in pregnancy].
AB  - Without anti-HIV treatment, mother to child HIV-I transmission occurs in 15-30%
      of HIV positive pregnancies. Transmission occurs mostly in the last trimester or
      at birth. The maternal virus load in the last trimester and around birth is
      strongly related to the risk of HIV transmission to the child. This risk can be
      reduced during pregnancy by anti-HIV treatment and in certain cases by performing
      a caesarean section. It is recommended to determine the plasma virus load several
      times during pregnancy. If the virus load is found to be high, measurement of
      plasma anti-HIV drug concentrations and anti-HIV drug resistance may prompt
      modification of the anti-HIV drug regimen with the objective of achieving maximal
      suppression of virus replication in the last trimester.

PMID- 10065236
TI  - [Vertical HIV-I-transmission. II. HIV-diagnosis in a child].
AB  - In newborn children from HIV-infected women early establishment of HIV infection
      is of importance for optimal therapy of HIV-infected children and avoidance of
      unnecessary medication in uninfected children. A more than 95% reliable diagnosis
      of HIV infection can now be obtained at the age of four weeks by polymerase chain
      reaction (PCR) technology. Before this age a positive PCR result is relevant
      since it necessitates additional investigation such as measuring anti-HIV drug
      resistance and may lead to modification of anti-HIV treatment. Prophylaxis
      against Pneumocystis carinii is not needed if HIV infection can not be
      demonstrated by PCR after the age of four weeks.

PMID- 10065237
TI  - [Abciximab: a new antiplatelet agent for use in coronary angioplasty].
AB  - Angioplasty of coronary arteries (PTCA) is an accepted treatment modality for
      patients with symptomatic coronary artery disease. Despite technological
      improvements it is still plagued by (mainly thrombotic) complications in around
      10% of all patients. A number of new antithrombotic and antiplatelet agents have
      been tried in the setting of angioplasty. The monoclonal glycoprotein IIb-IIIa
      receptor blocker abciximab appears to control the thrombotic process most
      effectively before, during and after the procedure. Three large randomized trials
      with abciximab in patients with stable, unstable or refractory unstable angina
      pectoris were conducted. All three showed a relative reduction by 35% to 56% in
      the primary combined endpoint, consisting of mortality, myocardial infarction or
      urgent intervention, at 30 days. Severe bleeding, which affected 14.0% of
      patients on abciximab in the first trial, was reduced, after adjusting heparin
      dosing and issuing sheath removal guidelines, to 3.8% in the second and 2.0% in
      the final study. In the placebo groups the percentages of severe bleeding were
      6.6, 1.9, and 3.1, respectively. Abciximab appears to reduce the thrombotic
      complications of PTCA substantially. The extent of this reduction and the
      severity of complications prevented justifies its more general use during
      angioplasty.

PMID- 10065238
TI  - [Clinical thinking and decision making in practice. A patient with pain in the
      upper abdomen].
AB  - A 74-year-old woman was admitted because of abdominal pain. A few weeks before
      this admission she had had a cerebral infarction in the right hemisphere,
      reflected by a left sided paralysis, dysarthria, depression and a slight
      cognitive disorder. The night before admission she woke up from a sharp,
      continuous pain in the right upper abdomen. Physical examination disclosed pain
      in the right upper abdomen on palpation. Laboratory tests showed a slight
      elevation of all 'liver' enzymes. A differential diagnosis of cholecystitis or
      pyelonephritis was made. Additional tests did not confirm either of these
      diagnoses. Because of immobilisation pulmonary embolism was then suspected. This
      diagnosis was confirmed by scintigraphy. The patient was treated and made a full
      recovery. Diagnostic errors can be made by faulty triggering and omitting
      verification. The diagnostic strategy for pulmonary embolism is a ventilation
      perfusion scan, which is followed in case of a non high-probability result by
      pulmonary angiography. It is emphasized that the presentation of pulmonary
      embolism can be aspecific.

PMID- 10065239
TI  - [Imported skin diseases].
AB  - In two Dutch subjects who had been on holiday in the tropics, a woman aged 32 and
      a man of Surinam descent aged 52 years, and in two men aged 21 and 38 years who
      had arrived from the tropics in the Netherlands, one recently and one 15 years
      previously, import skin diseases were diagnosed: larva migrans cutanea, cutaneous
      leishmaniasis, mycetoma and lobomycosis. The diagnosis was based on the
      anamnesis, the clinical picture and histopathological findings. The patients were
      cured by administration of antimicrobial agents and (or) excision. When
      travellers or immigrants from the tropics present with skin lesions, an imported
      skin disease should be considered.

PMID- 10065240
TI  - [The sentinel node procedure: standard intervention for surgical treatment of
      breast cancer].

PMID- 10065241
TI  - [A child with puzzling complaints--does he have a disease?].
AB  - Two children were presented to the physician with serious, long-lasting and
      unexplained complaints. The first was a girl aged four years with diarrhoea,
      vomiting and subfebrile temperature, the other was a boy aged almost 1 year with
      sudden spells of cyanosis and tachycardia. The mothers were found to falsify and
      fabricate the illness of their children: Munchausen syndrome by proxy. As a
      consequence of this behaviour, the children underwent extensive and sometimes
      invasive diagnostic investigations and treatment for their puzzling illness. A
      number of alarm signals associated with the condition, the parent and the child
      may help the physician to recognize and diagnose this syndrome at an early stage.
      Confrontation of the mother with the incriminating findings must take place under
      carefully prepared circumstances. The syndrome is related to the mothers' need
      for medical attention in order to retain a certain psychological balance. The
      fathers often have a passive role in the family life.

PMID- 10065242
TI  - [Acute management of patients bitten by poisonous snakes].
AB  - The management of poisonous snake bites includes first aid and clinical medical
      treatment. First aid consists of reassurement of the patient, immobilisation of
      the bitten limb and rapid transport to the nearest hospital to monitor the vital
      functions. In no case suction, incision or tight bandages should be applied. The
      degree of envenomation can be classified in three categories depending on the
      spread of the symptoms: no symptoms, only local non-progressive symptoms, and
      systemic or local rapidly progressive symptoms (severe envenomation). Antivenin
      therapy is indicated in severe envenomation. Because of the risk of anaphylactic
      reactions or serum sickness, antivenin should be given with great caution.
      Antibiotic therapy and tetanus prophylaxis are advised in all cases. Immediate
      consultation with the National Intoxication Centre of the Rijksinstitut voor
      Volksgezondheid en Milieu (RIVM) is always warranted; telephone: 030-2748888. In
      a national protocol, which is available at the RIVM, the Harbour Hospital
      Rotterdam, the Academic Medical Centre and Artis Zoo Amsterdam, the correct
      management of snake bites is described. An overview of all antivenins available
      in the Netherlands is also given in this protocol.

PMID- 10065243
TI  - [Who is the author and why? Will the scientific authorship be revised?].
AB  - There is much ado about medical and scientific authorship. The criteria for
      authorship as stated by the International Committee of Medical Journal Editors
      are debated. For readers, reviewers and editors it is of importance to know who
      is accountable and responsible for the contents of published articles. For
      researchers and clinicians on the one hand and for funding bodies and faculty
      management on the other disclosure of the individual contributions of authors to
      a publication is important. Editors are willing to play the role of intermediary
      between these two parties. This discussion has not come to a conclusion yet, but
      some journals (Journal of the American Medical Association (JAMA), British
      Medical Journal (BMJ), The Lancet) have already begun to publish the
      contribution(s) of individual authors (as stated by the authors themselves) at
      the end of their articles. The editors of the Nederlands Tijdschrift voor
      Geneeskunde (Dutch Journal of Medicine) are also going to ask for the authors'
      contributions from January 1, 1999 and intend to publish them later on in the
      year in the same way as The Lancet does. The maximum number of 6 authors that is
      allowed now, may be lapsed since the contributions of all authors will be known.

PMID- 10065244
TI  - [Benign symmetrical lipomatosis].
AB  - A man aged 51 for the last 3 months had displayed general malaise, epigastric
      pain, nausea, vomiting and constipation. Also, he had a pseudo-athletic
      appearance with symmetrical large accumulations of fat on the front of the trunk,
      the lower back, the shoulders and the proximal extremities, characteristic of
      'benign symmetrical lipomatosis'. He died of embolism of the aortic bifurcation
      and autopsy revealed an extensive adenocarcinoma in the upper abdomen, probably
      originating from the pancreas or the stomach. Benign symmetrical lipomatosis
      mostly occurs in middle-aged men. The pathogenesis is unknown. Association with
      alcohol abuse, metabolic abnormalities, polyneuropathy and certain malignancies
      has been described. Treatment is symptomatic by surgery or liposuction.

PMID- 10065245
TI  - [Metamorphopsia of the Alice in Wonderland-syndrome].
AB  - A boy aged 9 had had two years previously and again since a few weeks complaints
      of observing objects with distortion and reduction in size. He was known to
      suffer from asthma for which he received beclomethasone in a low dosage. Physical
      and supplementary examinations revealed no abnormalities. The condition was
      diagnosed as 'metamorphopsia'.

PMID- 10065246
TI  - [Chorea subsequent to acute rheumatic fever in a 9-year-old girl].
AB  - A nine-year-old girl had acute choreatic symptoms in her face and limbs, after a
      throat infection 6 weeks previously. On auscultation of the heart a systolic
      murmur was found and echocardiography showed mitral valve incompetence. There was
      a positive anti-deoxyribonuclease B titre in the serum, providing evidence of a
      previously contracted streptococcal infection. Both chorea and acquired carditis
      are major criteria for the diagnosis of acute rheumatic fever. The course was
      characterized--as it usually is--by spontaneous, gradual resolution of the
      symptoms. Protracted penicillin prophylaxis is indicated to prevent recurrence of
      acute rheumatic fever and cardiac valvular damage.

PMID- 10065247
TI  - [Pott's puffy tumor].
AB  - A 26-year-old man developed a fluctuating swelling of the forehead after twice
      being treated with antibiotics because of persistent sinusitis complaints. This
      swelling, a subperiostal abcess diagnosed as 'Pott's puffy tumor', is a
      complication of a frontal sinusitis, and may lead to serious neurological
      sequelae. The patient recovered after surgical drainage, ethmoidectomy and
      intravenous antibiotic treatment; no ablation of affected bone was necessary.

PMID- 10065248
TI  - [Poisoning with toxic plants in Curacao in 1766].
AB  - In the spring of 1766 a black supervisor in Curacao was the victim of attempted
      poisoning by a black practitioner or curador, engaged by two persons caught
      stealing by the supervisor. Data on the case were preserved in a letter from the
      Curacao director to the managers of the West-Indian Company in Amsterdam. In
      retrospect, the symptoms of the intoxication indicate that a similar mixture of
      toxic plants was used as described in 890 A.D. by the Arabic medical writer
      Wahshiya in his 'Book of Poisons': Calotropis procera and Pithecellobium unguis
      cati.

PMID- 10065249
TI  - ['Weight reduction preparations' from Thailand: unexpected complication for the
      traveller].
AB  - Two series of Thai 'slimming agents' purchased apparently without a medical
      consultation or prescription (one directly in Thailand and the other one
      indirectly in the Netherlands) were submitted for chemical analysis. Fenfluramine
      and diazepam were present in both series. One series also yielded phenolphtalein
      and vitamin B substances, while sennosides were found in the other series.
      Apparently travellers may unwittingly take along potent medicines when they
      return from far countries.

PMID- 10065250
TI  - [Memisa: from medical missionary action into a medical relief organization].
AB  - In the past seventy years Memisa Medicus Mundi has grown into an organization
      accounting for about half the annual number of Dutch health care workers in third
      world countries. On top of this, it gives financial and material support to many
      development programmes in Africa, Asia and Latin America. Of all aid, 82% is
      given to so-called structural programmes and 18% to disaster relief. Physicians
      who return to the Dutch health care system as general practitioners after a
      period abroad are capable of efficient practice management.

PMID- 10065251
TI  - [The administration of a clinical department].
AB  - The head of a clinical department, more than formerly, is a jack-of-all-trades:
      he leads his department, teaches, stimulates scientific research, arranges
      funding and administers clinical care. For the creative and renewing management
      nowadays required of him, he does not split off tasks, but he attempts to
      integrate them. Fritts' On leading a clinical department describes the position
      of today's manager, his style of leading and the various power strategies with
      which he can survive, for instance cooperative and delegating leadership.

PMID- 10065252
TI  - [Guideline 'Radiotherapy in non-small-cell lung carcinoma'].

PMID- 10065253
TI  - [Guideline 'Radiotherapy in non-small-cell lung carcinoma'].

PMID- 10065254
TI  - [Don't let the patient with Parkinson's disease fall!].
AB  - Three patients with a hypokinetic-rigid syndrome, a woman aged 69 years and two
      men aged 62 and 67 years, were admitted because of frequent falling. In two
      patients Parkinson's disease was diagnosed, the third had progressive
      supranuclear palsy. Balance impairment and falls typically emerge late in the
      course of Parkinson's disease. Falls can have dramatic physical consequences,
      such as (hip) fractures, and often induce a fear of additional falls which
      further impairs mobility and social contacts. The pathophysiology of falls in
      Parkinson's disease is complex and appears to result from both impaired balance
      regulation and commonly occurring balance disturbances (due to the shuffling gait
      and dyskinesias). Balance impairment often responds insufficiently to
      pharmacological treatment. Aspecific measures such as physical therapy, walking
      aids and reduction of domestic hazards can reduce the number of falls. Because
      patients often fail to voluntarily report their falls, physicians must actively
      pay attention to balance impairment in Parkinson's disease.

PMID- 10065255
TI  - [Nobel prize in Medicine and Physiology 1998 for the discovery of the role of
      nitric oxide as a signalling molecule].
AB  - The Nobel Prize for Medicine and Physiology 1998 was awarded to three American
      pharmacologists: Robert F.Furchgott, Louis J. Ignarro and Ferrid Murad for their
      work on nitric oxide as a signalling molecule in the cardiovascular system. This
      discovery is a classical case of serendipity. NO is an endothelium-derived factor
      which mediates local vasodilation. It protects the vascular system against
      atherosclerosis by various effects on leukocytes and vascular permeability. NO
      appears to be a universal signalling molecule in the body, involved in the
      inflammatory response, apoptosis and neurotransmission. Its biochemistry is
      closely linked to that of oxygen radicals.

PMID- 10065256
TI  - [The Organ Donation Law: changes in the procurement of organs and tissues for
      transplantation].
AB  - The Organ Donation Act fills an old gap in the legislation, leading to
      improvement of the legal position of those involved. Much attention is given to
      the protection of the potential donor. A new consent procedure is introduced,
      including the registration of the consent or refusal of all persons aged 18 years
      or older. Because of the persistent shortage of donor organs the noncommittal
      nature of organ procurement is changed. Hospitals and nursing homes are obliged
      to have a protocol for organizing tissue donation. Also, conditions have been
      created for a just division of the available organs and tissues for
      transplantation.

PMID- 10065257
TI  - [Immunosuppressive treatment of patients with a nephrotic syndrome due to minimal
      change glomerulopathy].
AB  - Prednisone monotherapy is the treatment of choice for patients with a nephrotic
      syndrome due to minimal change glomerulopathy. In adult patients treatment should
      be continued for at least 24 weeks. Within this period a remission of proteinuria
      will occur in 75 to 90% of the patients. Patients who do not respond
      satisfactorily to prednisone treatment can be treated with alkylating agents.
      Cyclophosphamide is the drug used most commonly. Prolonged treatment (> 12 weeks)
      is associated with a high risk of infertility. If alkylating agents cannot be
      used, prolonged treatment with ciclosporine is an option.

PMID- 10065258
TI  - [In-situ preservation of kidneys of 'non-heart-beating' donors: a possible way to
      offset the shortage of donor kidneys].
AB  - Every year some 700 new patients and 150 patients in whom a transplanted kidney
      is no longer functioning are placed on the waiting list for kidney
      transplantation. Per year some 400 cadaver kidneys and 100 kidneys from relatives
      and partners are transplanted in the Netherlands, resulting in an annual shortage
      of 350 kidneys. By 'non-heart-beating donor' is meant a subject deceased after
      cardiac arrest, in contradiction to the brain-dead donor. In non-heart-beating
      donors it is possible via a catheter in the inguinal artery to occlude the aorta
      above and below the kidney level, following which the kidneys may be perfused
      with a refrigerated fluid and preserved. In this way, time is gained to obtain
      consent for transplantation from the relatives or to find it in the donor
      registration. A kidney originating from a non-heart-beating donor relatively
      often starts to function only late after transplantation, or even does not begin
      to function at all. Nevertheless, the number of kidneys becoming available in
      this way suffices to eliminate the current shortage of donor kidneys. The Organ
      Donation Law allows cooling of the kidneys in the cadaver in expectation of
      consent for organ donation. It appears necessary to carry out a test of kidneys
      of non-heart-beating donors to avoid transplantation of non-viable kidneys.

PMID- 10065259
TI  - [The regional explantation team: an important contribution to organ procurement
      for transplantation in the Netherlands].
AB  - If organ donations concern not only the kidneys, but also the liver, pancreas
      and, sometimes, the heart and (or) lungs, several surgical removal teams, often
      from different (foreign) transplantation centres, may be involved. This has
      created organizatory problems resulting in loss of organs for transplantation. In
      the Nijmegen area since October 1994 a removal team has been active that in the
      regional donor hospital removes all abdominal organs from the donor on behalf of
      the various transplantation centres. This regional removal team performed 105
      multi-organ explanations in the period from October 1994 to December 1997. The
      reports that came back from the transplantation centres that had received the
      organs showed that none of these organs had been lost for transplantation through
      organizatory problems or anatomical damage. Experiences of operating room staff
      involved were positive: it was especially the standard surgical techniques and
      the quiet in the operating room that were appreciated. Special removal teams may
      greatly improve the evolution of organ donation in the Netherlands.

PMID- 10065260
TI  - [Lipodystrophy and 'buffalo hump' during treatment with HIV protease inhibitors].
AB  - In three patients, a 36-year-old HIV seropositive homosexual man and two women
      aged 35 and 59 years who had acquired HIV infection through heterosexual contact,
      signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The
      observed syndrome is seen after prolonged use of HIV protease inhibitors: it is
      characterized by peripheral fat wasting, central fat accumulation,
      hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue
      disappears resulting in prominent zygomata, veins and muscles and thinning of
      extremities and buttocks. In addition to abdominal fat accumulation, there have
      been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo
      hump. Lipodystrophy caused by protease inhibitors is a risk factor for
      cardiovascular disease. Recognition of the syndrome is essential for adequate
      follow-up and possible treatment.

PMID- 10065261
TI  - [Surveillance of AIDS and HIV infections in Amsterdam, 1997].
AB  - Data were collected in Amsterdam in 1997 from the aids surveillance, from the HIV
      surveillance among pregnant women and visitors of a clinic for sexually
      transmitted diseases (STD), and from two 'alternative' HIV test sites, using
      various survey systems. The findings were compared with those of previous years.
      Aids was diagnosed in 1997 in 123 patients, in 194 in 1996. Of the 354 patients
      in whom aids was diagnosed in 1993-1997 in a hospital recording additional
      information, 113 patients (32%) only learned that they had an HIV infection when
      aids was diagnosed in them. In 1997, out of 225 pregnant women with an increased
      risk of HIV infection, 10 were HIV seropositive (4.4%); in 1996, this proportion
      was 3/285 (1.1%). Among those attending STD clinics, HIV infection was observed
      approximately as frequently as in earlier years: about 1% of heterosexual men and
      women.

PMID- 10065262
TI  - [Kidney donation by a 'non-heart-beating' donor from an ethical perspective].
AB  - In asystolic patients, kidney donation is possible by using a non-heart-beating
      (NHB) donation procedure. This involves in situ perfusion of the kidneys by
      inserting a catheter into the femoral artery and flushing cold fluid through the
      kidneys. The introduction of an NHB donation programme leads to ethical questions
      concerning the guarantees for prudent procedure: How should death of a patient be
      defined in case of NHB donation? Is there a strict separation of responsibilities
      of the medical teams in the different phases of the procedure (patient treatment
      and actual donation procedure)? Are sufficient attention and care given to the
      relatives? Does the NHB donation procedure not interfere with the care of a
      patient who is expected to die soon? Extensive discussion with the Medical Ethics
      Committee of the University Hospital Nijmegen, the Netherlands, has led to a
      protocol for NHB kidney donation that meets the required guarantees.

PMID- 10065263
TI  - [The profile of a good doctor].
AB  - What is a good doctor? From the 12th to the 19th century the doctor was mostly an
      intellectual largely restricted to observing and describing symptoms and
      diseases. The 19th century saw the beginning of scientific insight into the
      causes of diseases. However, the primary objective of medical science is not to
      collect knowledge but to promote health. This involves both knowledge and art.
      Both arise from talent and education and are best achieved by early practical
      introduction to the basic subjects and scientific research, and during contacts
      with prominent teachers.

PMID- 10065264
TI  - [Sentinel node biopsy in breast cancer patients: recommendations for introduction
      of this technique].

PMID- 10065265
TI  - [Prone position favorable for infants' motor development].

PMID- 10065266
TI  - [Prone position favorable for infants' motor development].

PMID- 10065267
TI  - International Congress, anniversary meeting. 20 years Swiss Equine Veterinary
      Association. Luzern, 11-13 December 1998. Abstracts.

PMID- 10065268
TI  - 4th International Congress on Drug Therapy in HIV infection. Glasgow, United
      Kingdom, 8-12 November 1998. Abstracts.

PMID- 10065269
TI  - [International symposium on somatostatin analogues: fundamental aspects and
      clinical perspectives. Venice, Italy, 24-25 October 1997. Abstracts].

PMID- 10065270
TI  - [Dermatology meeting. Paris, France, 2-5 December 1998. Abstracts].

PMID- 10065271
TI  - Association for European Paediatric Cardiology XXXIII annual general meeting.
      Dublin, 10-13 June 1998. Abstracts.

PMID- 10065272
TI  - National Congress of Digestive Diseases. Milan, Italy, 14-18 November 1998.
      Abstracts.

PMID- 10065273
TI  - Poultry Science Association 19th annual meeting. State College, Pennsylvania,
      USA. August 2-5, 1998. Abstracts.

PMID- 10065274
TI  - [92nd French Congress of Urology. Paris, 17-20 November 1998. Abstracts].

PMID- 10065275
TI  - Society of American Gastrointestinal and Endoscopic Surgeons 1998 scientific
      session, Association of Endoscopic Surgeons of Great Britain and Ireland 1997 and
      1998 scientific sessions, and the National meeting of the Italian Society for
      Endoscopic Surgery 1998. Abstracts.

PMID- 10065277
TI  - [Incidence and predictive factors of mitral insufficiency in surgically treated
      aortic stenosis. Transthoracic and transesophageal ultrasonographic evaluation].
AB  - Mitral regurgitation is common in adults with aortic stenosis. When severe, it
      may aggravate the clinical condition and pose an additional therapeutic problem.
      The authors studied 40 consecutive patients with severe surgical aortic stenosis
      prospectively by transthoracic echocardiography and pre-operative
      transoesophageal echocardiography to determine the incidence, mechanism and
      degree of mitral regurgitation and its eventual relationship to the aortic
      stenosis. Mitral regurgitation was detected in all cases when both investigations
      were taken into consideration. It was usually mild, evaluated grade 2 by
      measuring the surface of the colour Doppler regurgitant jet, or mild to minimal
      of transoesophageal echocardiography in 35/40 patients (87.5% of cases). Rarely,
      a case of significant, autonomous mitral regurgitation (2 cases of valvular
      dystrophy, 1 pure severe mitral stenosis). On the other hand, calcification of
      the mitral annulus is common (14/40 patients, 35% of cases). The severity of the
      regurgitation in univariate analysis was significantly correlated mainly to the
      age of the patients (p = 0.027). The severity of the aortic stenosis (p = 0.0082)
      and the parameters related to the effects of stenosis, such as ventricular wall
      thickness and left atrial size. In multivariate analysis, the severity of the
      aortic stenosis and of its consequences were confirmed to play a role in the
      genesis of mitral regurgitation, the severity of which was correlated on
      transthoracic echocardiography to the aortic valve surface area and the left
      ventricular ejection fraction and, on transoesophageal echocardiography, to the
      transvalvular pressure gradient.

PMID- 10065278
TI  - [Comparison of apical and infundabular pacing in patients with primary dilated or
      ischemic cardiomyopathy].
AB  - Dual chamber pacing has been proposed as an alternative treatment to patients
      with cardiac failure refractory to optimal medical therapy. The influence of the
      site of ventricular pacing was studied in 15 patients with an average age of 68.7
      +/- 8.7 years with dilated cardiomyopathies and an average left ventricular
      ejection fraction of 22.3 +/- 6.8%. Three temporary USCI electrodes were
      positioned in the right atrium, the right ventricular outflow tract (RVOT) and
      the right ventricular apex. The average duration of the QRS complexes and the
      haemodynamic parameters (PAP, PCP and cardiac index) were measured in sinus
      rhythm and during DDD apical, RVOT and simultaneous apical and RVOT pacing. The
      RVOT and simultaneous pacing significantly reduced the QRS duration (135 +/- 14
      ms and 137 +/- 17 ms, p < 0.0001 respectively) compared with apical pacing (150
      +/- 19 ms). The mean PAP and mean PCP remained unchanged in the different modes
      of pacing but the cardiac index increased significantly during RVOT pacing (2.99
      +/- 0.67 l/min/m2) and simultaneous pacing (3 +/- 0.77 l/min/m2) compared with
      apical pacing (2.66 +/- 0.62 l/min/m2) (p < 0.001 and p < 0.01 respectively) and
      compared with sinus rhythm (2.62 +/- 0.7 l/min/m2) (p < 0.001 and p < 0.005
      respectively). This study suggests that better results may be obtained with RVOT
      screw in lead than with the traditional right ventricular apical electrode.

PMID- 10065279
TI  - [Radiofrequency ablation in auricular flutter. Predictive factors of primary
      success and medium term results].
AB  - Ninety-one consecutive patients underwent radiofrequency ablation of chronic or
      paroxysmal atrial flutter. The average age of the patients was 66. There was a
      previous history of atrial fibrillation in 38% of cases and of cardiac surgery in
      14.3% of cases. The primary success rate was 79% (92% in cases of common
      flutter). The predictive factors of success were the type of flutter (p < 0.001),
      left ventricular (p < 0.01) and left atrial dimensions (p < 0.01) at
      echocardiography. The length of the cavo-tricuspid isthmus measured by
      echocardiography had no influence on the initial result but, in primary success,
      did affect the parameters of the procedure (duration and number of applications
      of radiofrequency energy). After an average of 11 +/- 2 months, sinus rhythm was
      maintained in 67% of patients. There were recurrences of flutter in 27.5% of
      cases and of atrial fibrillation in 5.5% of cases: 85% of these episodes occurred
      during the first six months after ablation. A second procedure was carried out in
      12 patients for recurrence of flutter (92% primary success rate). After an
      average follow-up of 8.4 months, 4 patients had a recurrence and required a third
      procedure (100% success rate). In cases of failure of ablation, the rhythm was
      converted by a shock or atrial pacing: 47.3% of these patients remained in sinus
      rhythm with antiarrhythmic therapy with a 12 month follow-up. Radiofrequency
      ablation of atrial flutter is, therefore, a safe method, the difficulty of which
      is mainly related to anatomical factors: the medium-term results are better than
      those of other therapeutic methods.

PMID- 10065280
TI  - [Detection and surveillance of left atrial thrombosis by transesophageal
      echocardiography].
AB  - Out of 1,141 successive transoesophageal echocardiographic studies performed
      prospectively between 01/05/1993 and 31/12/1995, 26 cases of left atrial
      thrombosis were observed (2.2%); 5 were in the left atrium (20%), 19 in the left
      atrial appendage (73%) and the thrombi were in both atrium and left atrial
      appendage in 2 cases (7%). The 26 patients included 15 women and 11 men, with an
      average age of 69 +/- 16 years (range 25-89 years); 22 patients (84%) had
      permanent atrial fibrillation and 4 were in sinus rhythm. Only 5 of the patients
      were on oral anticoagulant therapy. All had underlying cardiac disease: 11 mitral
      valve diseases; 10 dilated cardiomyopathies; 2 hypertrophic cardiomyopathies; 3
      other cardiac diseases. The indication for transoesophageal echocardiography was
      systemic embolism in 13 cases (50%); before D.C. cardioversion in 10 cases (38%)
      and before percutaneous mitral valvuloplasty in 3 cases. The thrombus was
      adherent in 18 cases (69%) and mobile in 8 cases (31%). Spontaneous contrast was
      observed in 23 cases (88%). Intravenous heparin was given as soon as the
      diagnosis was made. In 4 patients, thrombectomy was indicated in view of the
      threatening nature of the thrombus and/or the necessity for associated valve
      replacement. In 22 patients, heparin was relayed by oral anticoagulants on the
      10th day of treatment. Control transoesophageal echocardiography was not
      performed because of the patient's refusal or poor general condition. The other
      15 patients were reexamined 1 to 5 times between the 4th day and 12th month: a
      regression was observed in 13 cases (86%) which was complete in 11 and partial in
      2 cases. No cases of embolism occurred during follow-up but six patients died: 1
      of the operated cases and 5 of the patients treated medically (3 cardiac failures
      and 2 cerebral haemorrhages). The authors conclude that left atrial thrombosis is
      rare in the absence of classical embolic cardiac disease. With the exception of
      the surgical indication of a life-threatening thrombus and/or associated surgical
      mitral valve disease, anticoagulant therapy results in complete or partial
      regression of the thrombus visualised by transoesophageal echocardiography which
      is essential for follow-up. The prognosis depends on the severity of the
      underlying heart disease.

PMID- 10065281
TI  - [Orthostatic hypotension due to autonomous nervous system dysfunction. Review of
      different syndromes and their treatment].
AB  - Dysfunction of the autonomous nervous system was poorly known to cardiologists
      until recently. Advances in the diagnosis of vasovagal syncope have initiated
      intense cardiological research into this subject. This type of syncope does not
      cover by far all dysfunctions of this system, all or nearly all of which have
      vasoplegic or bradycardic components. The aim of this article is to review the
      disorders of the autonomous nervous system which may interest every day practice
      of the cardiologist. The diagnostic advances and new treatments will require a
      further update of this review in the months or years to come.

PMID- 10065282
TI  - [Third degree atrio-ventricular block induced by interferon alpha. Report of a
      case].
AB  - Iatrogenic third degree atrioventricular block due to alpha interferon is rare.
      The authors present a case which occurred with low dosage, regressed when
      treatment was withdrawn and reappeared when treatment was reintroduced. The
      physiopathological mechanism of disease of the conduction pathways and its
      general cardiotoxicity is not yet understood. The secondary effects of this
      increasingly widely used anti-tumoral and anti-infectious drug should be
      recognised in order to prevent them. Initial cardiological investigation and
      follow-up are indicated to ensure this prevention.

PMID- 10065283
TI  - [Chronic occlusion of the left coronary artery].
AB  - Chronic occlusion of the left main coronary artery is rare with less than 100
      reported cases. the treatment is essentially surgical but medical management has
      been proposed. This case report illustrates the prognostic benefit of surgical
      management in view of the risk of secondary occlusion of the proximal right
      coronary artery.

PMID- 10065284
TI  - [Angioplasty and endoprosthesis of the left coronary artery. Report of a case].
AB  - The authors report the case of a 70 year old woman followed up in our Department
      for ischaemic heart disease since 1991 and admitted to the Intensive Care Unit in
      November 1996 for unstable angina. Coronary angiography showed significant
      stenosis of the left main coronary artery, a severe stenosis of the LAD and
      occlusion of the right coronary artery. Angioplasty of the middle segment of the
      LAD and left main coronary arteries with implantation of a stent was performed
      because of resistance to medical therapy and a contra-indication to surgery. Four
      months later, recurrent anginal pain led to a repeat angioplasty of the LAD with
      a satisfactory immediate result. The initial procedure on the left main coronary
      artery was successful and follow up was uncomplicated.

PMID- 10065285
TI  - [Traumatic coronary dissection caused by deceleration. Report of a case].
AB  - Myocardial infarction is a rare complication of traumatic thoracic deceleration.
      The authors report the case of anterior myocardial infarction with dissection of
      the left anterior descending artery in a 16 year old boy who was injured in a
      motorbike accident without a penetrating thoracic wound. Therefore, the only
      pathological mechanism was deceleration. The authors review the 12 previously
      reported cases.

PMID- 10065286
TI  - [Information of patients before stress test].

PMID- 10065287
TI  - [Patient information before coronarography].

PMID- 10065288
TI  - [Risk assessment preceding coronary angioplasty].

PMID- 10065289
TI  - [Information of patients preceding electrophysiologic diagnostic procedures].

PMID- 10065290
TI  - [Information of patients preceding radiofrequency ablation].

PMID- 10065291
TI  - Cervical cancer prevention for all Canadians.

PMID- 10065292
TI  - The three-tier system.

PMID- 10065293
TI  - Cutting and pasting in Quebec. Community health centres and health care reform.

PMID- 10065294
TI  - It is not about passing, it is about preparing.

PMID- 10065295
TI  - Concern for children everywhere.

PMID- 10065296
TI  - Medicine could learn from basketball.

PMID- 10065297
TI  - Northern British Columbia chronicle. Tales of a flown-in doctor.

PMID- 10065298
TI  - Young women taking isotretinoin still conceive. Role of physicians in preventing
      disaster.
AB  - QUESTION: One of my adolescent patients was prescribed isotretinoin for severe
      acne by a dermatologist. I was shocked to discover she does not use any means of
      contraception. The dermatologist insists he told her about the need for
      contraception. How can we do better? ANSWER: Clearly this dermatologist, like
      many of his colleagues, does not comply with the Pregnancy Prevention Program.
      Until physicians become more aware of this program, babies will continue to be
      born with embryopathy due to isotretinoin.

PMID- 10065299
TI  - Ophthaproblem. Diabetic retinopathy.

PMID- 10065300
TI  - Dermacase. Eccrine hydrocystoma.

PMID- 10065301
TI  - Medicolegal file. Tell everything you know about birth control pills.

PMID- 10065302
TI  - Risk factor for ectopic pregnancy.

PMID- 10065303
TI  - Practice tips. Management of pregnancy-induced nausea.

PMID- 10065304
TI  - Is misoprostol teratogenic? Misoprostol use during early pregnancy and its
      association with Mobius' syndrome.

PMID- 10065305
TI  - Does nebulized morphine offer symptom relief to patients with disabling dyspnea
      during end-stage disease?

PMID- 10065306
TI  - Residents' exposure to aboriginal health issues. Survey of family medicine
      programs in Canada.
AB  - OBJECTIVE: To determine whether Canadian family medicine residency programs
      currently have objectives, staff, and clinical experiences for adequately
      exposing residents to aboriginal health issues. DESIGN: A one-page questionnaire
      was developed to survey the details of teaching about and exposure to aboriginal
      health issues. SETTING: Family medicine programs in Canada. PARTICIPANTS: All
      Canadian family medicine program directors in the 18 programs (16 at universities
      and two satellite programs) were surveyed between October 1997 and March 1998.
      MAIN OUTCOME MEASURES: Whether programs had teaching objectives for exposing
      residents to aboriginal health issues, whether they had resource people
      available, what elective and core experiences in aboriginal health were offered,
      and what types of experiences were available. RESULTS: Response rate was 100%. No
      programs had formal, written curriculum objectives for residency training in
      aboriginal health issues, although some were considering them. Some programs,
      however, had objectives for specific weekend or day sessions. No programs had a
      strategy for encouraging enrollment of residents of aboriginal origin. Eleven
      programs had at least one resource person with experience in aboriginal health
      issues, and 12 had access to community-based aboriginal groups. Core experiences
      were all weekend seminars or retreats. Elective experiences in aboriginal health
      were available in 16 programs, and 11 programs were active on reserves.
      CONCLUSIONS: Many Canadian family medicine programs give residents some exposure
      to aboriginal health issues, but most need more expertise and direction on these
      issues. Some programs have unique approaches to teaching aboriginal health care
      that could be shared. Formalized objectives derived in collaboration with other
      family medicine programs and aboriginal groups could substantially improve the
      quality of education in aboriginal health care in Canada.

PMID- 10065307
TI  - Why do patients seek family physicians' services for cold symptoms?
AB  - OBJECTIVE: To examine the frequency of presentation to family physicians' offices
      for cold symptoms, the reasons for presentation, and the duration of symptoms
      before presentation. DESIGN: Prospective cross-sectional survey. PARTICIPANTS:
      One hundred consecutive patient encounters in each of 15 family practices from
      January 27 to February 3, 1994, involving both academic and non-academic family
      physicians in the London region. Data were collected prospectively using a
      checklist attached to each chart. MAIN OUTCOME MEASURES: Proportion of patients
      presenting with cold symptoms, reasons for presentation, number of days patients
      had had symptoms, billing code. RESULTS: A total of 1421 checklists were
      analyzed, 822 from academic practices and 599 from community practices.
      Proportion of presentations for cold symptoms was 14.8%, but visits coded as
      common cold represented 5.7%. Median number of days patients waited before
      presentation was 7.0; older patients tended to wait longer. Many patients were
      worried about developing complications (51.0%) or were fed up with their symptoms
      (31.9%). Most patients were between the ages of 20 and 64 (44.6%), and 57.6% of
      all patients had developed complications requiring treatment. CONCLUSIONS: The
      proportion of visits coded as common cold was lower than Ontario averages. Most
      patients had complications rather than simple colds and had managed their
      symptoms on their own for a fairly long time.

PMID- 10065308
TI  - Record linkage as a research tool for office-based medical care.
AB  - OBJECTIVE: To explore the feasibility of linking records to study health services
      and health outcomes for primary care patients. DESIGN: A cohort of patients from
      the Family Medicine Centre at Mount Sinai Hospital was assembled from the
      clinic's billing records. Their health numbers were linked to the Ontario
      Hospital Discharge Database. The pattern of hospital admission rates was
      investigated using International Classification of Diseases (ICD) codes for
      primary discharge diagnosis. A pilot case-control study of risk factor management
      for stroke was nested in the cohort. SETTING: Family medicine clinic based in a
      teaching hospital. PARTICIPANTS: A cohort of 19,654 Family Medicine Centre
      patients seen at least once since 1991. MAIN OUTCOME MEASURES: Admission rates by
      age, sex, and diagnosis. Numbers of admissions for individual patients, time to
      readmission, and length of stay. Odds ratios for admission for cerebrovascular
      disease. RESULTS: The 19,654 patients in the cohort had 14,299 discharges from
      Ontario hospitals in the 4 years from 1992 to 1995, including 3832 discharges
      following childbirth. Some patients had many discharges: 4816 people accounted
      for the 10,467 admissions excluding childbirth. Excluding transfers between
      institutions, there were 4975 readmissions to hospital during the 4 years, 1392
      (28%) of them within 28 days of previous discharge. Admissions for mental
      disorders accounted for the greatest number of days in hospital. The pilot study
      of risk factor management suggested that acetylsalicylic acid therapy might not
      be effective for elderly primary care patients with atrial fibrillation and that
      calcium channel blocker therapy might be less effective than other therapies for
      preventing cerebrovascular disease in hypertensive primary care patients.
      CONCLUSIONS: Record linkage combined with data collection by chart review or
      interview is a useful method for studying the effectiveness of medical care in
      Canada and might suggest interesting hypotheses for further investigation.

PMID- 10065309
TI  - Pap screening clinics with native women in Skidegate, Haida Gwaii. Need for
      innovation.
AB  - PROBLEM ADDRESSED: First Nations women in British Columbia, especially elders,
      are underscreened for cancer of the cervix compared with the general population
      and are much more likely to die of the disease than other women. OBJECTIVE OF
      PROGRAM: To develop a pilot program, in consultation with community
      representatives, to address the Pap screening needs of First Nations women 40
      years and older on a rural reserve. MAIN COMPONENTS OF PROGRAM: Identification of
      key links to the population; consultation with the community to design an
      outreach process; identification of underscreened women; implementation of
      community Pap screening clinics; evaluation of the pilot program. CONCLUSIONS: We
      developed a Pap screening outreach program that marked a departure from the usual
      screening approach in the community. First Nations community health
      representatives were key links for the process that involved family physicians
      and office staff at a local clinic on a rural reserve. Participation rate for the
      pilot program was 48%, resulting in an increase of 15% over the previously
      recorded screening rate for this population. More screening clinics of this type
      and evaluation for sustainability are proposed.

PMID- 10065310
TI  - Comprehensive computerized diabetes registry. Serving the Cree of Eeyou Istchee
      (eastern James Bay).
AB  - PROBLEM BEING ADDRESSED: Diabetes is rapidly evolving as a major health concern
      in the Cree population of eastern James Bay (Eeyou Istchee). The Cree Board of
      Health and Social Services of James Bay (CBHSSJB) diabetes registry was the
      initial phase in the development of a comprehensive program for diabetes in this
      region. OBJECTIVE OF PROGRAM: The CBHSSJB diabetes registry was developed to
      provide a framework to track the prevalence of diabetes and the progression of
      diabetic complications. The database will also identify patients not receiving
      appropriate clinical and laboratory screening for diabetic complications, and
      will provide standardized clinical flow sheets for routine patient management.
      MAIN COMPONENTS OF PROGRAM: The CBHSSJB diabetes registry uses a system of paper
      registration forms and clinical flow sheets kept in the nine community clinics.
      Information from these sheets is entered into a computer database annually. The
      flow sheets serve as a guideline for appropriate management of patients with
      diabetes, and provide a one-page summary of relevant clinical and laboratory
      information. CONCLUSIONS: A diabetes registry is vital to follow the progression
      of diabetes and diabetic complications in the region served by the CBHSSJB. The
      registry system incorporates both a means for regional epidemiologic monitoring
      of diabetes mellitus and clinical tools for managing patients with the disease.

PMID- 10065311
TI  - Investigating fatigue of less than 6 months' duration. Guidelines for family
      physicians.
AB  - OBJECTIVE: To develop an evidence-based systematic approach to assessment of
      adult patients who present to family physicians complaining of fatigue of less
      than 6 months' duration. The guidelines present investigative options, making
      explicit what should be considered in all cases and what should be considered
      only in specific situations. They aim to provide physicians with an approach
      that, to the extent possible, is based on evidence so that time and cost are
      minimized and detection and management of the cause of the fatigue are optimized.
      QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the key words
      "family practice" and "fatigue." Articles about chronic fatigue syndrome were
      excluded. Articles with level 3 evidence were found, but no randomized trials,
      cohort studies, or case-control studies were found. Articles looking specifically
      at the epidemiology, demographics, investigations, and diagnoses of patients with
      fatigue were chosen. Articles based on studies at referral and specialty centres
      were given less weight than those based on studies in family physicians' offices.
      MAIN MESSAGE: Adherence to these guidelines will decrease the cost of
      investigating the symptom of fatigue and optimize diagnosis and management. This
      needs to be proved in practice, however, and with research that produces level 1
      and 2 evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6
      months' duration should be assessed for psychosocial causes and should have a
      focused history and physical examination to determine whether further
      investigations should be done. The guidelines outline investigations to be
      considered. The elderly require special consideration. These guidelines have
      group validation, but they need to be tested by more physicians in various
      locations and types of practices.

PMID- 10065312
TI  - Screening for cervical cancer. Canadian programmatic guidelines.

PMID- 10065313
TI  - Conducting performance appraisals.

PMID- 10065314
TI  - Reducing HIV transmission.

PMID- 10065315
TI  - Paddling like mad underneath.

PMID- 10065316
TI  - Problems associated with the depopulation of tuberculosis-infected wapiti herds.

PMID- 10065317
TI  - Deans respond to Task Force report "opportunity for renewal".

PMID- 10065318
TI  - Veterinary ethics and conflict resolution.

PMID- 10065319
TI  - Observations on animal and human health during the outbreak of Mycobacterium
      bovis in game farm wapiti in Alberta.
AB  - This report describes and discusses the history, clinical, pathologic,
      epidemiologic, and human health aspects of an outbreak of Mycobacterium bovis
      infection in domestic wapiti in Alberta between 1990 and 1993, shortly after
      legislative changes allowing game farming. The extent and seriousness of the
      outbreak of M. bovis in wapiti in Alberta was not fully known at its onset. The
      clinical findings in the first recognized infected wapiti are presented and the
      postmortem records for the herd in which the animal resided are summarized.
      Epidemiologic findings from the subsequent field investigation are reviewed, the
      results of recognition and investigation of human exposure are updated, and
      recommendations for reduction of human exposure are presented.

PMID- 10065320
TI  - Surgical sterilization of free-ranging wolves.
AB  - The objective of the study was to determine whether surgical sterilization of
      both males and females in wolf pairs alters basic wolf social and territorial
      behaviors. Wolves were located from the air by snow-tracking methods and were
      tranquilizer-darted from a helicopter. Surgeries were performed either in a tent
      at the capture site or in a heated building in a nearby village. Six vasectomies
      and seven uterine horn ligations were performed in January and February of 1996
      and 1997. Two females died: one likely related to the capture procedure, the
      other of a peritonitis unrelated to the surgery. One wolf had a litter. None of
      the wolves have shown changes in behavioral patterns. Surgical sterilization can
      be effective, but other, less invasive, fertility control techniques should be
      investigated.

PMID- 10065321
TI  - Urethrorectal fistula in a horse.
AB  - Anomalies of the urethra are uncommon. Urethrorectal fistula in horses has only
      been reported in foals and only in conjunction with other congenital anomalies.
      This report describes the diagnosis, surgical management, and possible etiologies
      of a unique case of urethrorectal fistula in a mature gelding.

PMID- 10065322
TI  - Unusual case of foreign body-induced struvite urolithiasis in a dog.
AB  - A 6-year-old, castrated male dog was presented because of inappropriate urination
      and hematuria. Radiographs indicated a bladder stone with a sewing needle at its
      center. The urolith was removed and diagnosed as predominantly struvite, most
      likely a result of the foreign body and a urinary tract infection.

PMID- 10065323
TI  - An interesting case of pemphigus foliaceus in a dog.

PMID- 10065324
TI  - Primary hypoadrenocorticism in a dog receiving glucocorticoid supplementation.
AB  - A 5-year-old, spayed, female husky-Labrador retriever cross was diagnosed with
      primary hypoadrenocorticism, an uncommon endocrine disorder caused by a
      deficiency of glucocorticoid and mineralocorticoid hormones. Subtle clinical
      signs and previous treatment with exogenous glucocorticoid drugs required an
      adrenocorticotropic hormone stimulation test to confirm the diagnosis.

PMID- 10065325
TI  - Internet Web sites for veterinary practices.

PMID- 10065326
TI  - Barrier mechanisms in the brain, II. Immature brain.
AB  - 1. It is widely believed that 'the' blood-brain barrier is immature in foetuses
      and newborns. 2. Much evidence in support of this belief is based on experiments
      that were unphysiological and likely to have disrupted fragile blood vessels of
      the developing brain. Some confusion about barrier development arises from
      insufficient recognition that the term 'blood-brain barrier' describes a complex
      series of mechanisms controlling the internal environment of the brain. 3. We
      present evidence showing that the brain develops within an environment that,
      particularly with respect to protein, is different from that of the rest of the
      body and that possesses a number of unique features not present in the adult. 4.
      Barriers to protein at blood-brain and blood-cerebrospinal fluid (CSF) interfaces
      (tight junctions) are present from very early in development; immunocytochemical
      and permeability data show that proteins are largely excluded from extracellular
      space in developing brain. 5. Cerebrospinal fluid in developing brain contains
      high concentrations of proteins largely derived from plasma. This protein is
      transferred from blood by an intracellular mechanism across the epithelial cells
      of the immature choroid plexus. Only a small proportion of choroid plexus cells
      is involved. The route is an intracellular system of tubulo-endoplasmic reticulum
      continuously connected across the epithelial cells only early in brain
      development. 6. High concentrations of proteins in CSF in developing brain are
      largely excluded from the brain's extracellular space by barriers at the internal
      and external CSF-brain interfaces. These consist of membrane specializations
      between surfaces of cells forming these interfaces (neuroependyma on the inner
      surface; radial glial end feet on the outer surface). In contrast with tight
      junctions present at the blood-brain and blood-CSF barriers, at the CSF-brain
      barriers of the immature brain, other junctional types are involved: strap
      junctions in the neuroependyma and a mixture of junctions at the outer CSF-brain
      barrier (plate junctions, strap junctions and wafer junctions). These barriers
      are not present in the adult. 7. Permeability to small lipid-insoluble molecules
      is greater in developing brain; more specific mechanisms, such as those involved
      in transfer of ions and amino acids, develop sequentially as the brain grows.

PMID- 10065327
TI  - Adenosine and preconditioning revisited.
AB  - 1. Myocardial tolerance against infarction is substantially increased by exposing
      myocytes to 3-10 min transient ischaemia. In this phenomenon, termed
      'preconditioning', the adenosine receptor is one of the redundant triggers and
      the best characterized factor in the cardioprotective mechanism. 2. An increase
      in interstitial adenosine during preconditioning is thought to be derived
      primarily from hydrolysis of 5'-AMP in the myocyte by cytosolic 5'-nucleotidase,
      although a contribution of ectosolic 5'-nucleotidase remains controversial.
      Adenosine production during ischaemia is substantially suppressed in the
      preconditioned myocardium, probably due to a decrease in ATP utilization. 3. The
      adenosine receptor needs to be activated not only at the time of preconditioning
      ischemia, but also during ischaemic insult for the preconditioning to be
      cardioprotective. However, the extent of cardioprotection afforded by
      preconditioning is primarily determined by the interstitial adenosine level
      achieved during preconditioning ischaemia, not by the level during sustained
      ischaemia. These data suggest that a post-receptor mechanism downstream of the
      adenosine receptor may be up-regulated after preconditioning. 4. Studies in vitro
      suggest that the subtypes of adenosine receptor relevant to preconditioning
      against infarction are A1 and A3, the activation of which appears to provide
      additive protection. The functional interrelationship between these subtypes in
      vivo remains unknown. 5. An important step downstream of adenosine receptor
      activation is protein kinase C (PKC), which facilitates opening of ATP-sensitive
      potassium (KATP) channels, probably leading to enhancement of myocardial
      tolerance. However, activation of other protein kinases, such as tyrosine kinase,
      may also be important in preconditioning, depending on the animal species and
      preconditioning protocols. The PKC isoform and location of KATP channels (i.e.
      sarcolemmal vs mitochondrial KATP) that induce anti-infarct tolerance in myocytes
      remain to be identified.

PMID- 10065328
TI  - An action of erythromycin in the intestine that is not mediated via motilin
      receptors.
AB  - 1. Erythromycin lactobionate caused a concentration-dependent inhibition of nerve
      mediated contractions of the longitudinal muscle of the guinea-pig ileum, with a
      threshold for effect of 10-30 mumol/L. The non-antibiotic derivative of
      erythromycin ABT-229 had a similar effect, but was approximately 10-fold less
      potent. At a greater concentration (1 mmol/L), erythromycin also depressed the
      direct contractile effect of 10 mumol/L carbachol on the muscle. 2. Human/porcine
      motilin (up to 100 mumol/L) did not reduce the nerve-mediated contractions,
      although it did contract the muscle (threshold 30 mumol/L). Antagonists of
      motilin receptors (phe3leu13motilin, up to 1 mumol/L, and GM-109, up to 3
      mumol/L) did not reduce responses to erythromycin. 3. Erythromycin contracted the
      longitudinal muscle of the rabbit duodenum, with a threshold concentration of 0.1
      mumol/L and ABT-229 contracted this tissue at a threshold concentration of 0.01
      mumol/L. Effects of both agonists were antagonized by the motilin receptor
      antagonists phe3leu13motilin (0.3 mumol/L) and GM-109 (1 mumol/L). 4. It is
      concluded that the site(s) at which erythromycin acts in the guinea-pig ileum is
      not a motilin receptor and that ABT-229 is selective for the motilin receptor in
      comparison with non-motilin erythromycin sites and is unlikely to act at the
      latter site in therapeutic doses.

PMID- 10065329
TI  - Pulmonary inflammation without bronchial hyperresponsiveness in vivo or in vitro
      after sephadex instillation in pigs.
AB  - 1. In rodent models, Sephadex produces pulmonary inflammation that may be
      associated with bronchial hyperresponsiveness. In the present study we examined
      whether Sephadex-induced inflammation altered airway narrowing in pigs. 2. Twenty
      millilitres of 10 mg/mL Sephadex suspension was instilled twice intratracheally
      into anaesthetized pigs (days 1 and 7 of a 9 day study). In vivo bronchial
      responsiveness was assessed from the effect of acetylcholine (ACh) aerosol on
      airways resistance and dynamic compliance before Sephadex instillation and on
      days 3, 5 and 9. Lung histology and in vitro bronchial responsiveness was
      assessed on day 9. In vitro responsiveness was assessed by measuring the
      reduction in flow through perfused 2 mm i.d. bronchial segments in response to
      ACh applied luminally and adventitially. 3. Sephadex produced a focal
      peribronchial granulomatous reaction characterized by the presence of
      macrophages, eosinophils, neutrophils and giant cells. Changes in airway
      resistance and lung compliance in response to ACh did not change over the study
      period. The response of perfused bronchial segments to luminally or adventitially
      applied ACh was also unaltered. 4. Sephadex-induced pulmonary inflammation does
      not alter airway narrowing in vitro nor bronchial hyperresponsiveness in vivo in
      the pig.

PMID- 10065330
TI  - Effect of phosphorylation on L-type calcium current in ventricular myocytes
      dialysed with proteolytic enzymes.
AB  - 1. L-Type Ca2+ channels play important roles in cardiac excitation and
      conduction. The present study used the whole-cell patch-clamp technique to
      investigate properties of Ca2+ channels in guinea-pig isolated ventricular
      myocytes. The effects of internal application of the proteolytic enzymes trypsin
      and carboxypeptidase (CBP) on the whole-cell L-type Ca2+ current (ICa) were
      determined. When the effects of the enzymes on ICa had reached steady state, the
      effects of isoprenaline (ISP) or 2,3-butane-dione monoxime (BDM), which increase
      and decrease channel phosphorylation, respectively, were examined. The effects of
      these agents were compared with those observed in the absence of enzyme
      pretreatment. 2. The amplitude and inactivation characteristics of ICa during
      depolarizing voltage-clamp commands to +10 mV (0.1 Hz) were determined at 37
      degrees C. 3. Trypsin and CBP (both at concentrations of 1 mg/mL in the pipette
      solution) increased the amplitude of ICa 4.2- and 2.8-fold, respectively, and
      each enzyme increased the time constant of the slowly inactivating current by
      50%. 4. Trypsin decreased the potential at which ICa was half maximally activated
      from (mean +/- SD) -1.4 +/- 2.2 mV (n = 9) to -11.3 +/- 2.5 mV (n = 7). Although
      CBP increased ICa amplitude, it did not shift the half-maximal activation
      voltage. Maximum conductance was increased 5.3-fold by trypsin and 2.2-fold by
      CBP. 5. Isoprenaline (1 mumol/L) had no effects in myocytes dialysed with
      trypsin, but significantly increased the current in myocytes dialysed with CBP by
      8%. 6. At 12 mmol/L, BDM had no effect on current amplitude in the presence of
      trypsin, but decreased the time constant of slow inactivation to control values.
      After dialysis with CBP, BDM significantly decreased the maximum current by 11%
      and also decreased the rate of slow inactivation towards control values. 7. These
      data suggest that trypsin and CBP may have digested a part of the calcium channel
      that normally restricts current flow, but to different extents. The enzymes
      interacted with BDM and ISP in a fashion suggesting that two sites may influence
      the amplitude of the current and at least two other sites may influence the time
      course of the slowly inactivating current.

PMID- 10065331
TI  - Year-long clenbuterol treatment of mice increases mass, but not specific force or
      normalized power, of skeletal muscles.
AB  - 1. Clenbuterol has been proposed for the treatment of muscle wasting disorders,
      but its long-term effects on skeletal muscle function have not been tested
      rigorously. We tested the hypothesis that year-long treatment of young (6 months)
      mice with clenbuterol would increase skeletal muscle mass and in vitro
      measurements of specific force (Po) and power output. 2. Male mice (C57BL/10ScSn)
      were divided into treated (n = 6) or untreated (n = 8) groups. Treated mice
      received clenbuterol (1.5-2 mg/kg per day) in their drinking water for 52 weeks,
      following a staggered 3 day on/3 day off schedule to attenuate the response to
      clenbuterol. 3. Clenbuterol treatment increased the absolute mass of each muscle
      tested: the heart by 28%, extensor digitorum longus (EDL) by 16%, soleus by 22%
      and tibialis anterior by 17%. For treated compared with untreated mice, absolute
      Po (mN) was greater in soleus muscles but not different in EDL muscles. Absolute
      power output (mW) of the EDL and soleus muscles was not different and no
      differences were observed for the specific Po (kN/m2) or normalized power output
      (W/kg) of EDL muscles, soleus muscles or diaphragm muscle strips. 4. We conclude
      that, following year-long treatment of mice with clenbuterol, the mass of the
      heart and both fast and slow skeletal muscles is increased, but the lack of any
      change in normalized Po or power output indicates that clenbuterol has little
      therapeutic effect on the functional properties of skeletal muscle.

PMID- 10065332
TI  - Gender differences in sympathetic nervous system regulation.
AB  - 1. Females are protected against the development of hypertension. The purpose of
      the current review is to present the evidence for gender differences in the
      regulation of the sympatho-adrenal nervous system and to determine if these
      differences support the hypothesis that, in females, the regulation of the
      sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation
      is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control
      of sympatho-adrenal function is different in females and responses vary during
      the oestral and menstrual cycles. Pathways regulating the SNS appear to be less
      sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in
      females compared with males. 3. Gender differences in arterial baroreflex
      sensitivity suggest that females may have a greater baroreflex sensitivity, such
      that alterations in blood pressure are more efficiently controlled than in males.
      Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in
      females, possibly resulting in a greater renal excretory function. 4. An
      attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline
      (NA), suggests that gender differences in noradrenergic neurotransmission may
      protect females against sympathetic hyperactivity. Gender differences in the
      regulation of NA release via presynaptic alpha 2-adrenoceptors, the
      vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of
      catecholamines are consistent with this hypothesis. 5. Similarly, attenuated
      stress-induced increases in plasma catecholamines in women suggest that females
      are less sensitive and/or less responsive to adrenal medullary activation. This
      is supported by findings of gender differences in adrenal medullary catecholamine
      content, release and degradation. 6. We conclude that there is strong evidence
      that supports the hypothesis that, in females, the regulation of the SNS is
      altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal
      inhibition is augmented.

PMID- 10065333
TI  - Role of androgens in mediating hypertension and renal injury.
AB  - 1. Men are generally at greater risk for cardiovascular disease than are women,
      particularly with regard to enhanced progression of hypertension and loss of
      renal function. Despite these gender differences in the progression of
      hypertension and renal disease in humans and animals, the mechanisms responsible
      are unknown. 2. Castration in males has been shown to slow the progression of
      hypertension and ameliorate the loss in renal function. When serum testosterone
      was measured in the developing male spontaneously hypertensive rat (SHR), the
      peak serum testosterone level at 12 weeks coincided with the time when
      differences in systolic blood pressure could be measured between intact male SHR
      and females or castrated male SHR. Ovariectomy does not affect blood pressure in
      female SHR but testosterone treatment of ovariectomized females for 5 weeks
      results in exacerbation of hypertension almost to the level found in intact male
      SHR. These data strongly suggest a role for androgens in mediating the gender
      differences in hypertension. 3. The mechanisms by which androgens could increase
      blood pressure are not known. We have recently shown that, at comparable renal
      perfusion pressures, there is a hypertensive shift in the pressure-natriuresis
      relationship in male SHR compared with females or castrated male SHR.
      Testosterone treatment of ovariectomized female SHR also causes a rightward shift
      in the pressure-natriuresis relationship. 4. We hypothesize that androgens
      increase arterial pressure by causing a hypertensive shift in the pressure
      natriuresis relationship, either by having a direct effect to increase proximal
      tubular reabsorption or by activation of the renin-angiotensin system. We also
      hypothesize that the enhanced proximal tubular reabsorption leads to a
      tubuloglomerular feedback-mediated afferent vasodilation, which, in combination
      with the increase in arterial pressure, results in glomerular hypertension and
      renal injury.

PMID- 10065334
TI  - Gender differences and endothelium- and platelet-derived factors in the coronary
      circulation.
AB  - 1. Experiments were designed to determine whether or not interactions of
      platelets with coronary arteries are affected by gender or oestrogen-status. 2.
      Platelets and right coronary arteries were isolated from sexually mature male,
      female and ovariectomized pigs. Arteries were suspended in organ chambers for the
      measurement of isometric force. Responses of rings, with and without endothelium,
      were evaluated to aggregating platelets and the platelet products 5
      hydroxytryptamine (5-HT) and adenosine diphosphate (ADP). 3. Release of 5-HT,
      thromboxane A2 (TXA2) and prostacyclin were measured from platelets. 4. Platelets
      caused relaxations of rings with endothelium from all pigs. However, in rings
      without endothelium, consistent contractions were observed only in rings from
      male pigs. 5. The release of 5-HT and prostacyclin was greatest from platelets of
      ovariectomized pigs compared with male and female pigs. Release of TXA2 was
      greatest from platelets of male pigs. 6. Endothelium-dependent relaxations to ADP
      and contractions to 5-HT were similar among the three groups. 7. These results
      suggest that there may be gender-specific differences in vasomotor responses to
      autogenous platelets but not to the platelet-derived products 5-HT and ADP.
      Furthermore, there are gender differences in platelets in the release of cyclo
      oxygenase metabolites of arachidonic acid and 5-HT. These products could
      contribute to gender differences in response to injury in the coronary
      circulation.

PMID- 10065335
TI  - Oestrogen and transplant vascular disease.
AB  - 1. The aetiology of chronic rejection is clearly multifactorial and relates to
      both immunological and non-immunological factors. 2. Our studies suggest that the
      insulin-like growth factor (IGF)-I ligand and receptor genes are rate limiting in
      smooth muscle proliferation in the development of transplant arteriosclerosis. 3.
      Suppressing growth factor ligand or receptor expression could be effective
      strategies for the prevention or treatment of transplant arteriosclerosis. 4. We
      consistently find chronic oestradiol treatment of transplant recipients inhibits
      arteriosclerosis by attenuating both IGF-I expression and the immune response,
      particularly major histocompatibility complex class II expression. 5. Thus, a
      cell- or tissue-specific oestrogen with minimal feminizing properties may be an
      ideal drug for prevention of one of the major causes of loss of transplant
      function.

PMID- 10065336
TI  - Endothelins in health and disease: an overview.
AB  - 1. There is an ever increasing volume of evidence implicating endothelin-1 and
      its isoforms in a range of disease processes. These include asthma, pulmonary and
      essential systemic hypertension, cardiac failure and uterine dysfunction. 2.
      However, it is also important to realize that the endothelins play an obligatory
      role in normal cellular proliferation, repair and tissue development. 3. The
      present brief review focuses on some of the physiological and pathophysiological
      mediator roles of the endothelins and provides a sketch of the receptor systems
      and some of the signal transduction pathways that are now known to operate
      following receptor activation. 4. Importantly, it is now clear that the
      endothelins, their receptors and synthesis and degradation pathways offer
      potentially important therapeutic targets.

PMID- 10065337
TI  - Vascular biology of endothelin signal transduction.
AB  - 1. Endothelins regulate cell function by interacting with two classes of cell
      surface receptors, ETA and ETB receptors. Both receptor types are members of the
      heptahelical transmembrane-spanning receptor superfamily and couple via G
      proteins to multiple intracellular effectors. 2. Many of the cellular responses
      induced by endothelins are mediated by changes in cytoplasmic Ca2+ concentration.
      Stimulation of inositol 1,4,5-trisphosphate (IP3) formation promotes release of
      Ca2+ from intracellular stores via IP3-sensitive Ca2+ channels. This mechanism
      accounts for the initial transient peak of the Ca2+ elevation. The entry of Ca2+
      across the plasma membrane through multiple types of Ca2+ channels is responsible
      for the sustained phase of Ca2+ elevation and, together, both mechanisms regulate
      cell function. 3. Endothelin-mediated Ca2+ signals vary markedly in duration,
      spatial organization and temporal pattern. The elevations in Ca2+ are sustained,
      transient or oscillatory and occur either globally or are localized to discrete
      spatial domains. These different Ca2+ signals, which are dependent on the
      availability of specific ion channels, control distinct cellular functions.
      Ryanodine-sensitive Ca2+ release channels may be important in determining the
      organization of the Ca2+ signal. 4. Endothelin-induced Ca2+ elevations near the
      plasma membrane stimulate the opening of Ca(2+)-dependent K+ and Cl- channels.
      These channels are key regulators of membrane potential and, consequently,
      regulate the activity of voltage-dependent Ca2+ influx pathways. 5. Endothelin
      regulates the growth and differentiation of cells. It markedly potentiates the
      mitogenic response of other growth factors, an effect that involves activation of
      the mitogen-activated protein kinase cascade and induction of early response
      genes. 6. Finally, the vascular actions of endothelin are influenced by the
      relative expression of specific ion channels, the spatial and temporal pattern of
      the Ca2+ signal and the cellular composition of the vascular wall.

PMID- 10065338
TI  - Endometrial endothelin: regulator of uterine bleeding and endometrial repair.
AB  - 1. Endothelin (ET) and its mRNA are present in endometrium. Expression of ET
      varies across the menstrual cycle, reaching maximal levels in the premenstrual
      phase, suggesting a paracrine role in endometrial bleeding and/or repair. 2. The
      major cellular source of ET is the epithelium, although endothelium and
      decidualized stroma are additional sites of production. Epithelial ET is the ET-1
      isoform and this is able to contract rat thoracic aortic rings ex vivo. 3.
      Endothelin-1 production by cultured endometrial epithelial cells is markedly
      increased by serum and, to a lesser extent, by transforming growth factor-beta
      and interleukin-1 alpha, but not by epidermal growth factor, oxytocin, arginine
      vasopressin, thrombin or angiotensin II, which stimulate ET production in other
      tissues. 4. Endothelin-1 has mitogenic actions on endometrial stromal cells; it
      stimulates the uptake of [3H]-thymidine, acting via the AP-1 cis element c-jun.
      5. Neutral endopeptidase (NEP), a membrane-bound ectoenzyme that is capable of
      degrading ET, is localized principally in endometrial stroma and immunoreactivity
      is maximal in the secretory phase of the cycle. 6. A potential role for ET in
      regulating endometrial bleeding is suggested by studies on endometrium from two
      groups of women who were experiencing abnormal uterine bleeding: users of the
      contraceptive Norplant (Leiras Co., Turku, Finland) and subjects with documented
      menorrhagia. In both groups, ET-1 immunoreactivity in endometrial epithelium was
      markedly reduced compared with the normal menstrual cycle and did not vary
      cyclically, while NEP immunoreactivity, particularly in the epithelium, was
      increased. Thus, ET may be involved in endometrial bleeding, as a vasoconstrictor
      before the onset of menstruation when vasoconstriction is intense and,
      subsequently, when it may be required in the cessation of menstrual bleeding.
      Furthermore, the mitogenic actions of ET may play a role in endometrial
      regeneration and remodelling during the menstrual cycle, particularly following
      menstruation.

PMID- 10065339
TI  - Endothelin-1 as a mediator in cardiovascular disease.
AB  - 1. Brachial artery infusion of endothelin (ET)-1 causes transient vasodilatation
      followed by sustained vasoconstriction of the forearm vascular bed, whereas ET-1
      antagonists cause sustained vasodilatation. These data suggest that ET-1
      contributes to basal vascular tone. 2. Systemic infusion of ET-1 increases blood
      pressure and total peripheral vascular resistance and reduces heart rate and
      cardiac output. The renal and pulmonary circulations are particularly sensitive
      to the vasoconstrictor effects of ET-1. Systemic infusion of the ETA/B receptor
      antagonist TAK-044 reduces mean arterial pressure and peripheral vascular
      resistance. 3. Plasma ET-1 concentrations are not elevated in essential
      hypertension; however, insulin resistance may be a major determinant of plasma ET
      1 concentrations. Vascular sensitivity to ET-1 is normal or may be increased in
      essential hypertension. 4. Plasma ET-1 concentrations are increased in moderate
      and severe heart failure and are correlated with clinical and haemodynamic
      measures of severity. Endothelin-1 contributes to increased vascular tone in
      cardiac failure. 5. Plasma ET-1 concentrations increase following myocardial
      infarction and persistent elevation predicts an increased mortality within the
      subsequent 12 months. 6. Preliminary data suggest that interventions that reduce
      the activity of the endothelin system may have a beneficial effect in heart
      failure and myocardial infarction.

PMID- 10065340
TI  - Endothelin receptor distribution and function in the airways.
AB  - 1. Within the lung, endothelin (ET)-1 is synthesized and released by airway
      epithelial and vascular endothelial cells, as well as by inflammatory cells, such
      as macrophages. Following release, ET-1 can modulate the activities of a wide
      range of different cell types within the lung through the stimulation of specific
      endothelin ETA and ETB receptors. The present review focuses on recent advances
      in our understanding of the distribution and function of endothelin receptors
      within the airway wall and peripheral lung and, where possible, particular
      attention is given to studies using human cells, tissues and subjects. 2. The
      highest densities of endothelin receptors within the lung appear to be associated
      with airway smooth muscle and the alveolar septae. The relative proportions of
      ETA and ETB receptors present within these tissues display marked interspecies
      differences, although ETB receptors predominate at both sites in human lung. 3.
      The effects induced by ET-1 within the lung include contraction and proliferation
      of airway smooth muscle, facilitation of cholinergic neurotransmission, mucous
      gland hypersecretion, microvascular leakage and inflammatory cell influx and
      activation. There is also evidence that a proportion of ETB receptors in the
      pulmonary microvasculature act as clearance receptors for endothelin-1. 4.
      Evidence to date suggests that changes in the endothelin content within the
      airway wall, conceivably associated with lung pathology, are likely to have
      profound effects on the function of many cells within the lung.

PMID- 10065341
TI  - Putative mediator role of endothelin-1 in asthma and other lung diseases.
AB  - 1. There is an increasing amount of research to implicate endothelin (ET)-1, a
      member of a family of 21 amino acid peptides, as a potentially important mediator
      in pulmonary diseases, in particular asthma and pulmonary hypertension. Thus, ET
      1 fits several of the standard criteria that need to be fulfilled for a
      pathophysiologically relevant substance. 2. Endothelin-1 is present in abundance
      in human lung: the major loci for ET-1 are the epithelium, endothelium, endocrine
      cells and inflammatory cells. Furthermore, the receptors that mediate the
      biological effects of ET-1, the ETA and ETB receptor subtypes, are found in human
      lung, predominantly in airway smooth muscle, and vascular smooth muscle and, to a
      lesser extent, nerves. There is no change in the relative proportions of ETA and
      ETB receptors in asthmatic versus non-asthmatic bronchial smooth muscle and
      peripheral lung. 3. Several studies have shown that ET-1 mimics several of the
      features of asthma (including bronchospasm, airway remodelling, inflammatory cell
      recruitment and activation, oedema, mucus secretion, airway hyperreactivity and
      dysfunction in neuronal inputs); however, some other reports are at odds with
      these findings. 4. Endothelin-1 mimics the two classical features of pulmonary
      hypertension (pulmonary vascular constriction and remodelling), which is often a
      serious complication of chronic obstructive pulmonary disease. 5. Intranasal ET-1
      produces several of the symptoms of allergic rhinitis. 6. There are several
      reports of increased levels and/or expression of ET in patients with many
      pulmonary disorders, in particular asthma or pulmonary hypertension, with some
      evidence of a correlation between ET amounts and disease severity; however, other
      studies do not confirm these observations. 7. Despite these intriguing data in
      support of a pathophysiological role of ET-1 in lung disease, the definitive test
      and most difficult criteria to fulfil, the clinical evaluation of ET receptor
      antagonists or ET synthesis inhibitors, has still to be conducted. Only after
      these pivotal data are available will we be able to determine definitively
      whether ET-1 is a pathophysiologically important mediator in lung diseases or
      merely an interesting peptide with several effects in the pulmonary system.

PMID- 10065342
TI  - Regulation of vascular tone by endothelium-derived hyperpolarizing factor.
AB  - 1. Endothelium-derived hyperpolarizing factor (EDHF) mediates the nitric oxide
      (NO)-independent component of the relaxation in rat mesenteric arteries. The
      relationship between hyperpolarization and vascular tone was studied by
      simultaneous recording of membrane potential with intracellular microelectrodes
      and tension in ring segments of rat mesenteric arteries. 2. By depolarizing
      arteries with high potassium solutions, it was determined that the threshold for
      contraction is approximately -46 mV. Maximum contraction was attained when the
      arteries were depolarized to -20 mV. Thus, 1 mV depolarization resulted in an
      approximate 4% increase in tone. This relationship was not altered in
      spontaneously hypertensive rats. 3. Noradrenaline (0.3 mumol/L) caused
      contraction and depolarized arteries by 13 mV. Acetylcholine caused endothelium
      dependent relaxation and hyperpolarization up to 14 mV. In the presence of N
      omega-nitro-L-arginine, the EDHF-mediated relaxation was correlated to
      hyperpolarization. A hyperpolarization of 1 mV corresponded to a 4.3% decrease of
      the induced tone. 4. At concentrations (10 mumol/L) causing total relaxation, the
      maximum hyperpolarization induced by NO was only 7.6 mV. 5. A maximum relaxation
      of 88% was observed with pinacidil (3 mumol/L), despite a 25 mV
      hyperpolarization. Relaxations to NO and pinacidil were not correlated with
      hyperpolarization. At similar levels of hyperpolarization, NO and pinacidil
      elicited more relaxation than EDHF. 6. These studies show that vascular tone is
      very sensitive to membrane potential change in the range between -46 and -20 mV
      in the rat mesenteric artery. The relaxation response to EDHF, unlike that to NO
      and pinacidil, can be accounted for solely by its effect on the membrane
      potential.

PMID- 10065343
TI  - Endothelium-derived hyperpolarizing factor(s): species and tissue heterogeneity.
AB  - 1. Endothelium-derived relaxing factor is almost universally considered to be
      synonymous with nitric oxide (NO); however, it is now well established that at
      least two other chemically distinct species (prostacyclin (PGI2) and a
      hyperpolarizing factor) may also contribute to endothelium-dependent relaxation.
      2. Only relatively few studies have provided definitive evidence that an
      endothelium-derived hyperpolarizing factor (EDHF), which is neither NO nor PGI2,
      exists as a chemical mediator. 3. There is a lack of agreement as to the likely
      chemical identity of this putative factor. Some evidence suggests that EDHF may
      be a cytochrome P450-derived arachidonic acid product, possibly an
      epoxyeicosatrienoic acid (EET); conflicting evidence supports an endogenous
      cannabinoid as the mediator and still other studies infer an unknown mediator
      that is neither a cytochrome P450 nor a cannabinoid. 4. Data from our laboratory
      with a rabbit carotid artery 'sandwich' preparation have provided evidence that a
      mediator that meets the pharmacological expectations of a cytochrome P450 product
      is an EDHF. 5. Data from guinea-pig mesenteric arterioles suggest that EDHF is
      not a cytochrome P450 product, whereas in guinea-pig middle cerebral arteries,
      relaxation mediated by the NO/PGI2-independent mediator(s) is sensitive to
      cytochrome P450 inhibitors. In addition, in the rabbit middle cerebral artery, it
      is likely that endothelium-dependent hyperpolarization is mediated by both NO and
      PGI2. 6. In conclusion, these data indicate that EDHF is unlikely to be a single
      factor and that considerable tissue and species differences exist for the nature
      and cellular targets of the hyperpolarizing factors.

PMID- 10065344
TI  - Activation of vascular smooth muscle K+ channels by endothelium-derived relaxing
      factors.
AB  - 1. Endothelium-derived relaxing factors (EDRF), including nitric oxide (NO),
      prostacyclin (PGI2) and an as yet uncharacterized endothelium-derived
      hyperpolarizing factor (EDHF), are now recognized to induce relaxation of
      vascular smooth muscle, in part via the activation of K+ channels. 2. Experiments
      using selective K+ channel blockers, including iberiotoxin (IbTX), glibenclamide,
      apamin and 4-aminopyridine (4-AP) to inhibit endothelium-induced relaxation
      suggest that more than one type of K+ channel may be involved, depending on the
      species and tissue, including: (i) large conductance Ca(2+)-activated (BKCa)
      channels; (ii) ATP-sensitive (KATP) channels; (iii) small conductance Ca(2+)
      activated (SKCa) channels; and (iv) voltage-gated (Kv) K+ channels. 3. Recent
      observations suggest a role for Kv channels in some vessels based on a
      sensitivity of NO- and PGI2-mediated relaxations to 4-AP, as well as a complete
      suppression of EDHF-dependent relaxation by a combination of charybdotoxin (ChTX)
      and apamin but not IbTX and apamin. 4. The molecular identity of the K+ channels
      affected by EDRF is not well characterized. Recently, findings indicate that the
      pore-forming alpha-subunit tetramers of vascular smooth muscle BKCa channels are
      due to the expression of the so-called Slo channel gene. The identities of the
      KATP, SKCa and Kv channels involved in endothelium-dependent vasodilation are not
      known. 5. The component of whole-cell Kv current affected by PGI2 may be due to
      slowly inactivating, 4-AP-sensitive, 15 pS delayed-rectifier K+ channels (KDR);
      the activity of these channels in vascular myocytes is increased by forskolin and
      protein kinase A (PKA) and rabbit portal vein Kv1.5 pore-forming alpha-subunits,
      which appear to be a component of native KDR current and possess consensus
      phosphorylation sequences for PKA.

PMID- 10065345
TI  - On the accuracy of a new displacement instrumentation for rotary tablet presses.
AB  - The Portable Press Analyzer (PPA; Puuman Oy, Finland), a commercially available
      instrumentation for rotary tablet presses, was tested for accuracy of
      determination of force and displacement. The calibration of the force transducers
      (strain gauges) was tested under a static condition. The calibration of the
      displacement transducers (plastic film potentiometer) was compared for static and
      dynamic recordings. Force measurement was found precise (deviation < 1.1%) after
      alterations in the calibration procedure. Displacement measurement was affected
      by punch tilting and the application of the transducers. If tilting of punches
      was not considered, the deviation of displacement measurement from the true value
      (using steel tablets as a reference) was found up to 110 microns. By modifying
      the original PPA system by supplementing additional displacement transducers in
      the adjacent turret positions of the punches and adding a custom electronic
      device (Tilting Compensation Device), the accuracy of distance measurement was
      improved to 18.1 microns (+/- 3.64). Furthermore, machine and tooling deformation
      were recorded and found different under static and dynamic conditions. Correction
      of punch displacement for elastic deformation therefore should preferably be made
      from dynamic recordings.

PMID- 10065346
TI  - Evaluation of the in vitro and in vivo performance of two sustained-release
      lithium carbonate matrix tablets. Effect of different diets on the
      bioavailability.
AB  - Two sustained-release (SR) lithium carbonate (Li) matrix tablets, which use a
      hydrophilic (HP) matrix of hydroxypropylmethylcellulose (Methocel 4K MP) and a
      lipid (L) matrix of hydrogenated castor oil (Cutina HR) as sustaining agents,
      have been studied. In vitro performance through dissolution tests in different
      media was established. The L and HP formulations were affected by the composition
      of the dissolution media, and liberation was complete in 8 hr using a variable-pH
      medium that simulates the gastrointestinal (Gl) pH. Liberation was better
      described by the diffusional model of the square root of time for the L matrix
      and by zero-order kinetics for the HP matrix. Absolute bioavailability (BA) and
      food-induced changes on BA of both formulations were studied. The in vivo study
      design was a 4 x 4 Latin square involving 12 subjects who received two tablets of
      a 300-mg dose of SR formulations while fasting or with a standardized normal,
      high-fat, or high-fat/high-protein meal. The results for both formulations showed
      no differences in the disposition parameters and mean residence time when the
      tablets were administered with any type of diet. Changes in rate of absorption
      were found when both types of tablets were administered with any class of diet.
      The analysis of the ratio Cmax/AUC (area under the curve) evidenced that changes
      in Cmax were attributable to a higher rate of absorption for the HP matrix and to
      a higher amount absorbed for the L matrix. In the last, high-fat and high
      fat/high-protein diets produced higher AUCs than under fasting condition. The SR
      Li tablets formulated with hydrogenated castor oil were affected more by high-fat
      food, probably because of the increase of pancreatic and biliary secretions
      promoted by the meal, which would affect the matrix itself. The HP matrix was
      also affected, but to a lesser extent. The magnitude of the change in Cmax
      observed with this matrix probably is not important from a clinical point of
      view. Absolute BA was very low for the lipid matrix; in addition, since it is
      more seriously affected by food, probably it is not a good choice for a drug such
      as lithium. The in vivo behavior of the HP matrix makes it advisable to invest in
      efforts to achieve increased BA. Comparing in vitro and in vivo results, the
      focus should be achieving sustained, but complete, in vitro liberation in not
      more than 3 hr, with simulation of the transit time through the stomach and small
      bowel since lithium ion is only absorbed to this point.

PMID- 10065347
TI  - Formulation factors affecting drug release from poly(lactic acid) (PLA)
      microcapsule tablets.
AB  - A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet
      was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid)
      (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375
      to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug
      release from the microcapsule was influenced by the polymer ratios and increased
      with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and
      the PLA were directly compressed independently to form microcapsule and matrix
      tablets, respectively. Drug release from the microcapsule tablets was
      significantly lowered (p < .001) compared to matrix tablets or free microcapsule
      (free microcapsule > matrices > microcapsule tablets). We also investigated the
      effect of tablet adjuvants, compression pressures, and microcapsule loading on
      the tablet performance in terms of friability, hardness, porosity, tensile
      strength, and the release kinetics of PB. The drug release rate increased with
      increasing compression pressure in the case of Emcompress or lactose, but not
      Avicel. The drug release rate was three- to fivefold increased with sodium starch
      glycolate compared to tablets without a disintegrant. With an increase in
      microcapsule loading, a decrease in the drug release rate was observed; however,
      the tablet performance remained satisfactory. The morphology of the microcapsules
      was monitored microscopically after the dissolution and the disintegration of
      tablets. The drug release accelerated with compression pressures and microcapsule
      loading from the tablets due to mechanical destruction of the microcapsule wall,
      which was more clearly seen after disintegration and dissolution of the tablets.
      Our data suggest that the PLA microcapsule can be tableted to make a SR product
      without significantly affecting its release kinetics.

PMID- 10065348
TI  - Rheological characterization of hydroxypropylcellulose gels.
AB  - The present paper describes the rheological properties of hydroxypropylcellulose
      (HPC) gels formulated in propylene glycol (PG), water, ethanol, and mixtures of
      these components. The effects of molecular weight, polymer concentration, and
      solvent composition on the apparent viscosity and flow characteristics have been
      studied by continuous shear rheometry. The HPC gels are shear thinning and do not
      exhibit significant yield or hysteresis in their rheograms. The apparent
      viscosity increases with increasing molecular weight and concentration of the
      polymer, as expected. Although not so pronounced at lower concentrations (< or =
      1.5%), HPC gels tend to become increasingly non-Newtonian with increasing
      molecular weight at higher polymer concentrations (3%). A mathematical model has
      been proposed for the prediction of viscosities of HPC gels. There exists a high
      degree of dependence on molecular interactions between various solvent molecules
      in the prediction of mixture viscosities in ternary systems. The effects of
      solvent composition on the viscoelastic behavior of these gels have also been
      examined by dynamic mechanical analysis. The HPC gels are highly viscoelastic and
      exhibit greater degrees of elasticity with increased PG content in ternary
      solvent mixtures with water and ethanol. The study also suggests that dynamic
      mechanical analysis could prove to be a useful tool in the determination of zero
      shear viscosities, viscosities that are representative of most realistic
      situations.

PMID- 10065349
TI  - Effect of powder substrate on the dissolution properties of methyclothiazide
      liquisolid compacts.
AB  - The effects of powder substrate composition on the in vitro release properties of
      methyclothiazide liquisolid compacts were evaluated. The dissolution patterns of
      this water-insoluble drug formulated in liquisolid tablets were also compared to
      those of commercial products. According to the new liquisolid technique, liquid
      medications such as solutions or suspensions of water-insoluble drugs in suitable
      nonvolatile liquid vehicles can be converted into acceptably flowing and readily
      compressible powders by a simple admixture with certain powder substrates, which
      are selected powders referred to as the carrier and coating materials. Enhanced
      release profiles may be exhibited by such systems due to the increased wetting
      properties and surface of drug available for dissolution. Liquisolid tablets of
      methyclothiazide containing a 5% w/w drug solution in polyethylene glycol 400
      were prepared using powder substrates of different excipient ratios. The release
      rates of such products were assessed using the USP dissolution test and were
      compared to those of their commercial counterparts. It was observed that maximum
      drug dissolution rates can be exhibited by systems that have powder substrates
      with optimum carrier-to-coating ratios. In addition, liquisolid tablets displayed
      significantly enhanced dissolution profiles compared to those of marketed
      products.

PMID- 10065350
TI  - Relationship between the swelling process and the release of a water-soluble drug
      from a compressed swellable-soluble matrix of poly(vinyl alcohol).
AB  - An attempt was made in this study to relate the release of a highly water-soluble
      model drug from tablet matrices of poly(vinyl alcohol) (PVAL) with the factors
      that may affect the release behavior. Swelling was evaluated using a simple
      projection method. The swollen layer was photographed to monitor its thickness.
      The polymer and drug dissolution were determined simultaneously by
      spectrophotometric methods. The resulting change of tablet area showed that the
      process of swelling occurred in three different stages that were intimately
      related to polymer dissolution: (a) a rapid initial swelling, resulting in an
      increased area; (b) a period with an approximately constant area; and (c) a
      decrease of the tablet area. In spite of the significant dissolution of PVAL
      during the release process, the thickness of the gel layer gradually increased.
      Thus, the delivery was governed by the drug concentration gradient along the
      diffusional path length. The drug release appeared to be controlled by a
      diffusion process according to Higuchi-type kinetics. The data analysis of drug
      and polymer profiles confirmed the diffusional mechanism.

PMID- 10065351
TI  - Formulation of a charcoal suspension for intratumoral injection. Study of
      galenical excipients.
AB  - To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery,
      thus allowing a better localization of the remaining tumor by the surgeon, we
      developed a formulation containing 10% charcoal suspended in water for parenteral
      preparations. The present study concerns a new step in the development of the
      charcoal suspension. We sought to determine whether the addition of various
      excipients could improve the formulation properties and affect the labeling of
      tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate
      80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and
      mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated
      silica. Except for glucose and mannitol, which were added at a 5% concentration,
      the other excipients were added at a 0.1% concentration, they were dissolved in
      water for parenteral injection and sterilized at 120 degrees C for 20 min. We
      then measured diffusion in vivo in mammary tumor. In vivo, when injected
      intratumorally in mice, a greater diffusion of charcoal particles was noted
      within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40,
      and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol).
      Pluronic F68 slightly improved the stability of the suspension and did not lead
      to marked diffusion at the injection site, but it showed slight toxicity and
      cannot be used in the formulation. We concluded that the best formulation was an
      aqueous 10% micronized peat charcoal suspension.

PMID- 10065352
TI  - Controlled-release hydrophilic tablets for individualized theophylline therapy.
AB  - Directly compressible controlled-release (CR) theophylline tablet formulations
      with a non-zero-order drug release were prepared using various grades of
      Methocels. These tablet formulations were employed in the individualization of
      therapy with the aid of a pharmacokinetic simulation model developed with STELLA
      II computer software. In vitro drug release data were used to simulate plasma
      concentration-time (C,t) profiles based on a wide range of previously reported
      patient pharmacokinetic parameters (clearances of 2-5 L/hr and apparent volumes
      of distribution of 20-50 L). The simulations indicated that formulations
      containing low-viscosity Methocels (E4, K4, and K4CR) were suitable for
      individualizing theophylline therapy. Average steady-state concentrations were
      well within the therapeutic range of 10-20 micrograms/ml. High-viscosity polymers
      such as E10CR, K15, and K15CR yielded subtherapeutic concentrations and were
      deemed unsuitable. Thus, a pharmacokinetic simulation program capable of
      predicting in vivo C,t profiles (even though theophylline release occurred by a
      non-zero order) may be useful for individualizing theophylline therapy that
      involves CR formulations.

PMID- 10065353
TI  - Physicochemical characterization of glybuzole polymorphs and their pharmaceutical
      properties.
AB  - Systematic polymorphic screening tests were performed using 11 kinds of solvents
      and 6 kinds of preparation methods, and the three specific modifications of
      glybuzole (forms I and II and amorphous form) were identified by X-ray
      diffractometry and differential thermal analysis (DTA). The physicochemical
      properties of forms I and II and amorphous forms were measured using X-ray
      diffractometry, differential scanning calorimetry (DSC), thermogravimetry (TG),
      scanning electron microscopy (SEM), solubility tests, and others. The
      solubilities of all modifications in JP XII, first and second fluid (pH 1.2 and
      6.8, respectively) were evaluated at 37 degrees C. Forms I and II and the
      amorphous form showed almost equivalent solubilities. Forms I and II were stable
      polymorphic forms at 0% and 75% relative humidity (RH), respectively, at 40
      degrees C for 2 months, but the amorphous form was not stable. The
      crystallization rates of the amorphous form at 0% and 75% RH at 40 degrees C were
      estimated by X-ray diffraction analysis based on the Jander equation, and the
      rate at 0% RH was 364 times slower than that at 75% RH.

PMID- 10065354
TI  - Effects of crystalline form on the tableting compression mechanism of
      phenobarbital polymorphs.
AB  - The effects of the polymorphic form on the compression mechanism of forms A, B,
      and F of phenobarbital were investigated using a compression simulator, mercury
      porosimetry, X-ray diffraction analysis, BET gas absorption method, and scanning
      electron microscopic (SEM) photography. The order of tablet hardness obtained
      from all phenobarbital polymorphs was form A > form B > form F in accordance with
      that of the specific surface area. The Cooper and Eaton method was applied to
      evaluate two individual compression processes: particle rearrangement (phase I)
      and fragmentation and/or deformation (phase II). The parameters for compression
      processes were calculated using a nonlinear regression analyses program, and the
      compression energies of phases I and II were calculated from these parameters.
      The relationship between specific surface area after compression and compression
      energy at phase I showed a good linear correlation, but their ratio did not. In
      contrast, the specific surface area ratio showed a linear relationship with the
      compression energy on phase II, but again the ratio of these two parameters did
      not. The tablet hardness showed a linear relationship with the specific surface
      area ratio, but not with the specific surface area. Again, the ratio of these two
      parameters did not show a linear relationship.

PMID- 10065355
TI  - Sampling bias in blending validation and a different approach to homogeneity
      assessment.
AB  - Sampling of batches studied for validation is reported. A thief particularly
      suited for granules, rather than cohesive powders, was used in the study. It is
      shown, as has been demonstrated in the past, that traditional 1x to 3x thief
      sampling of a blend is biased, and that the bias decreases as the sample size
      increases. It is shown that taking 50 samples of tablets after blending and
      testing this subpopulation for normality is a discriminating manner of testing
      for homogeneity. As a criterion, it is better than sampling at mixer or drum
      stage would be even if an unbiased sampling device were available.

PMID- 10065356
TI  - Effect of packaging and storage on the stability of carbamazepine tablets.
AB  - The effect of packaging and storage on carbamazepine (CBZ) tablets was examined
      using Tegretol and Tegral, dispensed in strip seals, and Finlepsin, dispensed in
      bottles. Tegretol and Tegral tablets were stored in their original strips at 40
      degrees C, 50 degrees C, and 60 degrees C for 6 months, 3 months, and 1 month,
      respectively, at 75% relative humidity (RH). Also, tablets were removed from
      their strips, placed in bottles, and exposed daily to 97% RH at 40 degrees C for
      5 min for 30 days. Finlepsin tablets were exposed to 97% RH at 25 degrees C or 40
      degrees C for 1 month by removing bottle caps daily for 5 min. Dissolution was
      used to assess in vitro tablet performance, and high-performance liquid
      chromatography (HPLC) was used to evaluate the chemical stability of CBZ. Results
      show that Tegretol tablets were not affected by the tested stress conditions.
      Tegral tablets, stored in their strips at 50 degrees C or 60 degrees C and 75%
      RH, showed increased disintegration and dissolution. The effect of 40 degrees
      C/75% RH for 6 months was similar to 1-month storage at 40 degrees C/97% RH; the
      tablets hardened and dissolved less than fresh Tegral tablets. Removal of Tegral
      tablets from their original strips resulted in only 7% dissolved in 60 min. For
      Finlepsin, the effect of 97% RH at 40 degrees C was more profound than 97% RH at
      25 degrees C, but both conditions caused a decrease in dissolution, the extent of
      which was dependent on tablet position in the bottle. Stressed CBZ tablets,
      however, showed no change in the chemical stability of CBZ under all tested
      conditions.

PMID- 10065357
TI  - Evaluation of Eudragit RS-PO and Ethocel 100 matrices for the controlled release
      of lobenzarit disodium.
AB  - Lobenzarit disodium is a drug for the treatment of rheumatoid arthritis. In this
      work, inert matrix tablets of lobenzarit disodium were prepared by direct
      compression using Ethocel 100 and Eudragit RS-PO as polymeric materials in
      different ratios. The obtained powder mixtures and tablets were evaluated from
      the rheological and technological points of view. The dissolution test was
      performed to evaluate the in vitro release kinetic of the matrices. The obtained
      dissolution profiles demonstrated that the matrices containing Eudragit RS-PO
      showed a slower release rate and therefore were more suitable for controlling the
      release of drug. The fit to the Higuchi model indicates that the drug release
      mechanism from these matrices was controlled by the diffusion step.

PMID- 10065358
TI  - In vitro release and diffusion studies of promethazine hydrochloride from
      polymeric dermatological bases using cellulose membrane and hairless mouse skin.
AB  - The study was designed to investigate the feasibility of developing a transdermal
      drug dosage form of promethazine hydrochloride (PMH). The in vitro release and
      diffusion characteristics of PMH from various dermatological polymeric bases were
      studied using cellulose membrane and hairless mouse skin as the diffusion
      barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose
      (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose
      sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the
      effects of several additive ingredients known to enhance the drug release from
      topical formulations were evaluated. The general rank order for the drug release
      from these formulations using cellulose membrane was observed to be PEG > HMPC >
      Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had
      little or no effect on the drug diffusion from these bases, except for the
      hydrophilic ointment formulation containing 15% ethanol, which provided a
      significant increase in the drug release. However, when these formulations were
      studied for drug diffusion through the hairless mouse skin, the Avicel CL-611
      base containing 15% ethanol exhibited the optimum drug release. The data also
      revealed that this formulation gave the highest steady-state flux, diffusion, and
      permeability coefficient values and correlated well with the amount of drug
      release.

PMID- 10065359
TI  - Ketoprofen suppository dosage forms: in vitro release and in vivo absorption
      studies in rabbits.
AB  - In vitro release of ketoprofen from suppository bases and in vivo absorption in
      rabbits were studied. Suppositories containing 50 mg of ketoprofen were prepared
      using theobroma oil, esterified (c10-c18) fatty acids, and polyethylene glycol
      1000 bases. The displacement values of the drug were determined and found to be
      of the order of theobroma oil > esterified (c10-c18) fatty acids and polyethylene
      glycol 1000 bases. The suppository hardness data revealed that the theobroma oil
      base produced relatively brittle suppositories. Using the USP dissolution method,
      the release of ketoprofen was observed to be greatest from polyethylene glycol
      1000 suppositories. With the dialysis technique, the maximum release of drug was
      obtained from theobroma oil suppository containing polysorbate 40 at a 6% level.
      Selected suppository formulations were evaluated for rectal absorption studies in
      rabbits. The in vivo data showed that the optimum drug absorption took place from
      the polyethylene glycol 1000 base and theobroma oil formulation containing 6%
      polysorbate 40.

PMID- 10065360
TI  - Formulation design and optimization of modified-release microspheres of
      diclofenac sodium.
AB  - The present study deals with the preparation of microspheres of diclofenac sodium
      using cross-linked poly(vinyl alcohol) (PVA). A central composite design
      consisting of a two-level full factorial design superimposed on a star design was
      employed for developing the microspheres. The PVA to the drug ratio X1 and amount
      of glutaral-dehyde cross-linking agent X2 were chosen as the independent
      variables. The time required for 50% drug dissolution t50 in phosphate buffer (pH
      7.2) was selected as the dependent variable. An optimum polynomial equation was
      generated for the prediction of the response variable t50. Based on the results
      of multiple linear regression analysis and F statistics, it may be concluded that
      sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2
      interaction was found to be statistically significant. A response surface plot is
      presented to show the effects of X1 and X2 on t50. The drug release pattern fit
      the Higuchi model well. A model was validated for accurate prediction of the drug
      dissolution profile with constraints on the percentage drug release in the first,
      fifth, and seventh hours. The data of a selected batch were subjected to an
      optimization study, and an optimal formulation was fabricated. Good agreement was
      observed between the predicted and the observed dissolution profiles of the
      optimal formulation.

PMID- 10065361
TI  - Adsorption of calcitonin to glass.
AB  - Surface adsorption of calcitonin on soda lime silica glass was investigated. An
      attempt was also made to examine the effect of additives on the inhibition of
      calcitonin adsorption. Results showed that the adsorption isotherms were of the
      Langmuir and Freundlich type, depending on pH. Less adsorption was found for
      calcitonin at pH 4.3. The addition of nonionic surfactants such as Pluronic F68
      and Tween 80 to the calcitonin solutions demonstrated inhibition of absorption
      and reduction of adsorption rate. The addition of chlorobutanol also showed the
      effect of minimizing adsorption.

PMID- 10065362
TI  - The Vanderbilt University Center in Molecular Toxicology: the first 30 years.

PMID- 10065363
TI  - Predicting drug interactions and pharmacokinetic variability with in vitro
      methods: the olanzapine experience.

PMID- 10065364
TI  - Modulation of drug metabolism in infectious and inflammatory diseases.
AB  - During inflammation, expression of various P450 genes is modulated
      differentially. Both the downregulation of some P450s and the induction of others
      may be the result of a complex interaction involving inflammatory cytokines,
      stress hormones, and metabolic perturbations. Our results suggest that NO is not
      an important mediator for the downregulation of CYP2C11 in rat liver.

PMID- 10065365
TI  - Modeling the chemoprotective functions of glutathione S-transferases in cultured
      cell lines by heterologous expression.

PMID- 10065366
TI  - Kinetic and chemical mechanism of epoxide hydrolase.

PMID- 10065367
TI  - Role of Kupffer cells in peroxisome proliferator-induced hepatocyte
      proliferation.

PMID- 10065368
TI  - The isoprostanes: unique prostaglandin-like products of free-radical-initiated
      lipid peroxidation.
AB  - The discovery of IsoPs as products of nonenzymatic lipid peroxidation has opened
      up new areas of investigation regarding the role of free radicals in human
      physiology and pathophysiology. The quantification of IsoPs as markers of
      oxidative stress status appears to be an important advance in our ability to
      explore the role of free radicals in the pathogenesis of human disease. An
      important need in the field of free-radical medicine is information regarding the
      clinical pharmacology of antioxidant agents. Because of the evidence implicating
      free radicals in the pathogenesis of a number of human diseases, large clinical
      trials are planned or underway to assess whether antioxidants can either prevent
      the development or ameliorate the pathology of certain human disorders. However,
      data regarding the most effective doses and combination of antioxidant agents to
      use in these clinical trials is lacking. As mentioned previously, administration
      of antioxidants suppresses the formation of IsoPs, even in normal individuals.
      Thus, measurement of IsoPs may provide a valuable approach to define the clinical
      pharmacology of antioxidants. In addition to being markers of oxidative stress,
      several IsoPs possess potent biological activity. The availability of additional
      IsoPs in synthetic form should broaden our knowledge concerning the role of these
      molecules as mediators of oxidant stress. Despite the fact that considerable
      information has been obtained since the initial report of the discovery of IsoPs
      [6], much remains to be understood about these molecules. With continued research
      in this area, we believe that much new information will emerge that will open up
      additional important new areas for future investigation.

PMID- 10065369
TI  - Kinetics of hydrolysis and reaction of aflatoxin B1 exo-8,9-epoxide and relevance
      to toxicity and detoxication.

PMID- 10065370
TI  - Strategies to enhance the coexpression of cytochrome P450 2E1 and reductase in
      bacteria.

PMID- 10065371
TI  - The mechanism of bioactivation of N-nitrosodiethanolamine.

PMID- 10065372
TI  - Flavodoxin as a model for the P450-interacting domain of NADPH cytochrome P450
      reductase.

PMID- 10065373
TI  - P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in
      extrahepatic tissues.
AB  - Historically, there has been intense interest in P450 metabolic oxidation,
      peroxidation, and reduction of xenobiotics. More recently, there has been a
      growing appreciation for the role of P450s in the oxidation of lipophilic
      endobiotics, such as bile acids, fat-soluble vitamins, and eicosanoids. This
      review details the emerging CYP2J subfamily of P450s and their role as catalysts
      of arachidonic acid metabolism.

PMID- 10065374
TI  - Benzylamine analog binding studies as probes of the substrate sites of monoamine
      oxidases A and B.

PMID- 10065375
TI  - Role of canonical glucocorticoid responsive elements in modulating expression of
      genes regulated by the arylhydrocarbon receptor.

PMID- 10065376
TI  - Reactions of prostaglandin endoperoxide synthase with nitric oxide and
      peroxynitrite.

PMID- 10065377
TI  - Vestibular evoked myogenic potentials in acoustic tumor patients with normal
      auditory brainstem responses.
AB  - In order to clarify the utility of the vestibular evoked myogenic potential
      (VEMP) in detecting acoustic tumors, we report two patients who were found to
      have normal auditory brainstem responses (ABRs) and abnormal VEMPs. To record
      VEMPs, electromyographic responses to brief loud clicks (0.1 ms at 95 dBnHL) were
      amplified and averaged on the sternocleidomastoid muscle ipsilateral to the
      stimulated side. The stimulation rate was 5 Hz and the analysis time 50 ms. The
      first case was a 54-year-old woman in whom VEMPs were absent on the affected side
      while caloric tests and ABRs were normal. The second case was a 58-year-old woman
      whose VEMPs were absent on the affected side while caloric tests revealed a 22%
      canal paresis and normal ABRs. These results and previous studies suggested that
      the VEMP could reflect a function different from those evaluated by the ABR or
      the caloric test. We concluded that the VEMP can provide useful information in
      diagnosing acoustic tumors.

PMID- 10065378
TI  - Mastoid pneumatization and aging in children with Pierre-Robin syndrome and in
      the cleft palate population out of syndrome.
AB  - We examined the characteristics of mastoid pneumatization in the Pierre-Robin
      syndrome (PRS) and non-PRS cleft palate population in relation to age. There were
      14 patients with PRS (median age, 5 years), 7 patients with bilateral cleft lip
      palates (BCLP: median age, 6 years), 29 patients with unilateral cleft lip
      palates (UCLP: median age, 6 years) and 15 patients with isolated cleft palates
      (ICP: median age, 7 years). All had secretory otitis and ventilation tubes
      inserted. Pneumatization was assessed by standard computerized planimetric
      methods. Temporal bone (Schuller view) X-rays were obtained. Areas of bone
      pneumatization were outlined and measured separately for each ear. The median
      pneumatized area of the mastoid (MBP) in PRS patients (6.73 cm2) was
      significantly lower than in non-PRS cleft patients (7.29 cm2). It was also lower
      than in UCLP (7.35 cm2; P = 0.01) and ICP (7.19 cm2; P = 0.02). MBP did not
      change significantly with age in PRS (Spearman rs = 0.11) and BCLP (Spearman rs =
      0.11), but did increase significantly in the ICP group (Spearman rs = 0.23; P =
      0.04). Cubic regression showed the best fit in the BCLP (r2 = 0.61; P = 0.01) and
      ICP (r2 = 0.10; P = 0.05). It was not significant for PRS (r2 = 0.132) or UCLP
      (r2 = 0.049). We concluded that pneumatization in all cases increases with age,
      but it is statistically significant only in ICP. PRS patients have a lower area
      of mastoid air-cell size than the non-PRS cleft palate population. The extent of
      mastoid pneumatization in PRS patients does not correlate with age because of the
      negative influence of the mandibular hypoplasia and glossoptosis present.

PMID- 10065379
TI  - Hereditary hemorrhagic telangiectasias: a challenge for the clinician.
AB  - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) remains a
      challenge for all clinicians, as in about 80% of cases nasal bleeding is the
      first manifestation of this disease, which is characterized by a clinical triad
      of multiple telangiectasias, recurrent hemorrhages and familial occurrence.
      Although in the last few years there has been diagnostic and therapeutic
      progress, a cure for this rarely life-threatening but often burdening and
      handicapping disease is still not possible. We have reviewed head and neck
      presentations, diagnostic and therapeutic features, as well as new insights into
      the molecular genetics of the disease and local treatment now available.

PMID- 10065380
TI  - Chemosensory event-related potentials to trigeminal stimuli change in relation to
      the interval between repetitive stimulation of the nasal mucosa.
AB  - Event-related potentials (ERPs) to olfactory and trigeminal stimuli have been
      used commonly to evaluate chemosensory dysfunction. The aim of the present study
      was to investigate how ERPs could be modified by repetitive stimulations of the
      intranasal trigeminal nerve using 52% v/v CO2 stimuli for 200 ms periods. Nine
      subjects were exposed to 6 sessions each during which trains of 16 stimuli were
      applied. The interval between stimuli was constant for each experiment, but
      varied between experiments (10, 20, 30, 40, 60, and 90 s). Trigeminal ERPs were
      obtained from three positions on the skull. Both intensity ratings and ERP
      amplitudes decreased as the interstimulus interval (ISI) shortened. Specifically,
      ratings and response amplitudes were most strongly reduced by approximately 30
      50% at the shortest ISI used (10 s) and were largest at an ISI of 90 s. The
      decrease of amplitudes was strongest for the P46 amplitude. Our findings suggest
      that this may be the result of both habituation and stimulus predictability. We
      hypothesize that the ISI dependence of chemosensory ERPs may also be a function
      of an interaction between Adelta and C fibers.

PMID- 10065381
TI  - Pleomorphic adenoma of the auricle.

PMID- 10065382
TI  - [Optimal early therapy of epilepsies--therapeutic strategies and research leads].

PMID- 10065383
TI  - [Combined alcohol dependence and personality disorder and its legal consequences
      with respect to commitment].
AB  - People frequently consuming an excessive amount of alcohol often show symptoms of
      personality disorder. Personality disorder and alcohol dependence are frequently
      connected with each other. However, there are only very few conditions enhancing
      concomitant dependence and personality disorder to the rank of a mental disease
      according to German guardianship legislation. If the patient's condition meets
      the criteria of a psychic disease and endangers his own health and public safety,
      commitment to a mental hospital or guardianship are justified. The purpose of
      this clinical analysis was to compare the medical proposal for treatment with
      legal prerequisites which are indispensable for involuntary admission to a mental
      hospital. Whereas the Psychiatric Disorders Act intends to avert danger to the
      public, guardianship legislation aims at individual help. We present a patient
      who suffered from alcoholism and simultaneously met criteria of a serious
      personality disorder, which was classified according to ICD-10 (F 60.31). As the
      aggravation of the symptoms was most likely to entail serious danger to his
      health the judge ordered immediate involuntary admission. Two other patients had
      similar comorbidity but had to be released from hospital because of finalisation
      of detoxification. Neither dependence nor personality disorder were pronounced
      enough to restrict the rights of the individual. Our analysis shows that the
      psychiatrist must present with an expert medical report that quantifies the
      extent of alcoholism and personality disorder and characterises them as psychic
      disease. Consequently, for the purpose of quantifying the extent of dependence,
      we recommend to apply the European Addiction Severity Index whose suitability
      should be assessed.

PMID- 10065384
TI  - [Encephalopathies caused by valproate].
AB  - Valproic acid (VPA)-induced encephalopathy is a rarely considered side effect,
      with somnolence, reduced motor activity and severe deterioration of cognitive and
      behavioural abilities. In accordance with the increasing clinical importance of
      valproate clinical symptoms, causes and possibilities of treatment are reviewed
      by reporting on two cases of valproate-induced encephalopathy. In comparison to
      VPA intoxication, which is associated to increased VPA blood levels, the
      mechanisms of encephalopathy may include interactions of the hepatic enzymes, a
      direct toxic effect on the cerebral receptors, as well as drug interactions, a
      paradoxical epileptogenic effect and metabolic interactions. In most cases
      withdrawal of VPA produces regression of the symptoms within a few days; the role
      of L-carnitin or citrullin supplementation in clinical treatment remains unclear.

PMID- 10065385
TI  - [Folk medical practices in psychiatric patients of Turkish origin in Germany].
AB  - The treatment of Turkish patients is peculiar due to differences of socio
      cultural background and speech. Magic conceptions of pathogenesis and nosogeny
      have a broad acceptance in a part of population. Magic faith healers, Hocas, are
      authorities to be consulted for treatment. In ritual acts they intend to stave
      off noxious influences and to strengthen the healing power with sacred formulas
      and through powerful objects. To investigate the importance, utilisation and
      attitude towards the Hocas of Turkish psychiatric patients living in Germany we
      conducted an interview with 55 psychiatric inpatients. Our findings were a
      reduced importance of Hocas due to influences of the Western culture and modern
      medicine. "Folk" medicine is still important for patients with psychic disorders
      and is used parallel to modern medical facilities.

PMID- 10065386
TI  - [What characterizes the problem psychiatric patient? Results of a study of
      patient descriptions using the Psychiatric Personnel Order].
AB  - In recent years, economic pressure on extended and repeated psychiatric
      hospitalisation have increased dramatically. At the same time, diagnostic
      approaches, e.g., the new concept of the "young adult chronic patient" have
      improved. The first part of this article summarises reports and experiences on
      the chronic mentally ill and the so-called "heavy users" of psychiatric
      hospitalisation. Although the number of studies evaluating this group is small,
      several characteristics can be identified. Subsequently, a study is presented
      that deals with psychiatric problem patients in a special way, namely the A2
      categorisation according to the German Psychiatric Personnel Regulation
      (Psychiatrie-Personalverordnung [Psych-PV]). The study is based on 170
      consecutive admissions to the Department of General Psychiatry of a large German
      state hospital, who are characterised as normal (A1) and intensive patients (A2),
      respectively. The study aimed at describing difficult-to-treat patients or those
      whose treatment demands large human resources. Medical histories,
      sociodemographic and psychopathological data as well as subjective health status
      data of these patients were analysed by standardised and validated instruments
      (e.g., BPRS, CGI, SF-36, GAF). Results show that the patients under study
      suffered mainly from schizophrenic psychosis according to ICD-9. Patients
      categorised into A2 showed a high degree of psychopathology and little insight
      into their disease. Further it can be demonstrated that they used more
      therapeutic help from general practitioners rather than from specialists in
      psychiatry prior to admission. In conclusion, it is suggested to evaluate
      concepts, e.g., new treatment methods in respect of motivating schizophrenic
      patients, new typological methods to better diagnosis and to treat psychiatric
      problem patients via new treatment modalities such as Case Management or
      inpatient settings for double diagnoses.

PMID- 10065387
TI  - [Direct and indirect costs of schizophrenia].
AB  - In the present study the costs of schizophrenia in Germany were studied using the
      "bottom up" prevalence-based method. In a random sample of 180 schizophrenic
      patients stratified according to the most important care institutions, direct and
      indirect costs were retrospectively documented for a 12-month period. Depending
      on the place of recruitment and the extent of care provided, total yearly costs
      result between about DM 33,000 for a patient treated predominantly on an
      outpatient basis and about DM 126,000 for a patient requiring hospital care and
      about DM 135,000 for a patient in job rehabilitation. The direct yearly treatment
      costs were, as expected, lowest for patients recruited in the private practice of
      a psychiatrist and predominantly treated on an outpatient basis (DM 5,788), and
      were the highest in the psychiatric hospital (DM 64,661) and in job
      rehabilitation (DM 79,996). In the patients recruited in the outpatient domain,
      doctors' fees and medication together were responsible for only 4.5% of the total
      costs, whereas the indirect costs (e.g., through work incapacity) were
      responsible for 87% of the total yearly costs. For methodological reasons the
      total costs caused by schizophrenic psychoses in Germany per year can at present
      be estimated only roughly. A conservative estimate is between 8.5 and 18 billion
      DM per year. The study shows that schizophrenia is a very expensive illness, the
      direct and indirect costs of which are on the whole comparable to those of the
      common somatic illnesses. Therefore, also for economical reasons, sufficient
      financial means should be invested in the research and treatment of this severe
      illness.

PMID- 10065388
TI  - [Disorders of consciousness: the basis for ethical assessment].
AB  - During the past few years there is an ethical debate about neurological disease
      entities that are characterised by a) prolongation of life owing to medical
      treatment, b) limited chances of cure, and c) impaired to unbearable life
      quality: akinetic mutism, vegetative state ("Wachkoma", apallic syndrome), and
      locked-in syndrome. These are compared to typical coma and brain death. According
      to Gerstenbrand (1967) [34] the vegetative state is differentiated into the
      transitional state following typical coma, the variations of typical and
      incomplete vegetative state, the remission state and the "Durchgangssyndrom"
      (characterized by preserved wakefulness with affective lability, disorientation,
      and amnesia). With regard to pathogenesis we differentiate posttraumatic and
      posthypoxic origin and variable lesions in cerebral cortex, thalamus or
      mesencephalic reticular formation. Uncertainty of prognosis is stressed. In
      respect of brain death we compare a) neocortical death, b) brain stem death, and
      c) whole brain death, and discuss problems of difficult delimitation and
      uncertainty of diagnosis. These syndromes are compared to anencephaly and
      hydranencephaly. Regarding the locked-in syndrome, typical, incomplete and
      complete (total) forms are distinguished. The differential diagnosis between the
      complete locked-in syndrome and brain stem death seems problematic. Difficulties
      in decisions limiting therapeutic effort stem from a) essentially intuitive
      judgement about observations, b) variability of syndromes and courses, c)
      uncertainty of prognosis, and d) differences in understanding and valuation
      throughout society. Emphasis is on a trustful and open colloquy among the persons
      concerned.

PMID- 10065389
TI  - Offspring of women with eating disorders.
AB  - OBJECTIVE: We evaluated health and development, temperament, body satisfaction,
      nutritional status, and mealtime interaction patterns in offspring (ages 1-4) of
      women with current or past anorexia and/or bulimia nervosa in comparison to
      control children. METHOD: Information was gathered via maternal report and
      interview, health and development records, a 3 day food diary, and a videotaped
      lunchtime interaction. RESULTS: Children of women with eating disorders had
      significantly lower birth weights and lengths than control children. There were
      no differences observed in childhood temperament or mothers' satisfaction with
      children's appearance. Mothers with eating disorders had more difficulty
      maintaining breastfeeding and they made significantly fewer positive comments
      about food and eating than control mothers during the mealtime observation.
      DISCUSSION: Feeding behavior in women with eating disorders appears to be
      problematic from pregnancy through the toddler years and has various
      manifestations from low birth weight, to difficulties with breast feeding, to
      detached and noninteractive mealtimes. Although these factors are unlikely to
      cause eating disorders, they may contribute to a permissive environment in which
      a genetic predisposition is more likely to be expressed.

PMID- 10065390
TI  - Atypical anorexia nervosa: separation from typical cases in course and outcome in
      a long-term prospective study.
AB  - OBJECTIVE: To assess differences in long-term course and outcome between typical
      and atypical cases of anorexia nervosa. METHOD: A naturalistic, longitudinal
      prospective design was used to assess recovery, relapse, and onset of binge
      eating over 10 to 15 years in patients ascertained through a university-based
      specialty treatment program. Atypical anorexia nervosa was distinguished from the
      diagnostically prototypic form of the disorder based on the continuous absence of
      morbid fear of weight gain and body size distortion during the inpatient phase of
      treatment. Patients were assessed semiannually for 5 years then annually
      thereafter until the final visit. RESULTS: Compared to pure cases of anorexia
      nervosa, atypical cases were less likely to drop weight after discharge,
      recovered more rapidly, and had lower cumulative risk for developing binge
      eating. CONCLUSION: It has been argued recently that weight phobia and body image
      disturbance should not be viewed as critical to the diagnosis of anorexia
      nervosa. This study shows that the absence of these particular symptoms in
      patients presenting with malnutrition secondary to extreme dietary restriction
      predicts a less malignant course and outcome compared to typical cases of
      anorexia nervosa. These course differences suggest that the division of patients
      into typical versus atypical diagnostic subtypes may be nosologically valid and
      clinically useful.

PMID- 10065391
TI  - Predictors of bone mineral density in patients with eating disorders.
AB  - OBJECTIVE: The objective of this study was to examine potential clinical
      predictors of bone density in patients with eating disorders. METHOD: We studied
      137 women with anorexia nervosa, bulimia nervosa, or eating disorder not
      otherwise specified (NOS) after admission to the hospital. Clinical data of
      patients were collected by clinical interview and standardized questionnaires.
      Bone mineral density of the lumbar spine was measured by dual energy x-ray
      absorptiometry. RESULTS: Lumbar bone density was significantly correlated to
      present and past minimum weight even after correction for height and age. Other
      factors did not reach significance. CONCLUSION: Normalized present and past
      weight is the best predictor of lumbar bone density in patients with eating
      disorders. Factors like reduced caloric intake, binge eating, vomiting, menstrual
      status, and use of estrogen, laxatives, and nicotine seem to have no independent
      effect on bone density in this group of patients.

PMID- 10065392
TI  - Binge eating before the onset of dieting: a distinct subgroup of bulimia nervosa?
AB  - OBJECTIVE: While most individuals with bulimia nervosa begin dieting prior to the
      onset of binge eating, some individuals begin binge eating prior to dieting. The
      purpose of this study was to assess the differences between these two groups.
      METHODS: Participants (N = 120) in a treatment study for bulimia nervosa were
      separated into two groups (Binge First vs. Diet First) based on the ages they
      reported for the onset of binge eating and of dieting and then compared across a
      number of variables. RESULTS: Individuals in the Binge First group reported
      higher weight, higher shape and weight concern, lower age of onset of eating
      disorder symptoms, and an altered relationship of binge eating to vomiting when
      compared to individuals in the Diet First group. DISCUSSION: The differences
      between the two groups suggest that there may be subgroups of individuals with
      purging bulimia nervosa and that individuals in the Binge First group more
      closely resemble individuals with binge eating disorder than do those in the Diet
      First group.

PMID- 10065393
TI  - A greater role of emotional than physical or sexual abuse in predicting
      disordered eating attitudes: the role of mediating variables.
AB  - OBJECTIVE: Previous research on the role of trauma in eating psychopathology has
      generally focused on reported childhood sexual abuse. There has been relatively
      little research addressing the full range of abusive experiences, and none
      considering their long-term impact on eating. This study investigated the
      relationships between four forms of reported childhood abuse (physical abuse,
      sexual abuse, emotional abuse, neglect) and unhealthy eating attitudes in adult
      life. Within this relationship, depression, anxiety, and dissociation were
      considered potential mediators, and age of onset of abuse was considered a
      potential moderator. METHOD: A nonclinical sample of 236 women completed self
      report measures of abuse, eating psychopathology, and psychological function.
      Multiple regression analyses were used to test for associations as well as for
      mediating and moderating influences. RESULTS: When the intercorrelations of the
      different forms of reported abuse were controlled for, emotional abuse was the
      only form of childhood trauma that predicted unhealthy adult eating attitudes.
      That relationship was perfectly mediated by the women's levels of anxiety and
      dissociation. Age at onset of emotional abuse did not moderate these
      relationships. DISCUSSION: Although these results require extension to a clinical
      sample, the findings underscore the need to consider a history of emotional
      trauma as a potentially central factor in any abusive history. Treatment may
      depend on addressing the psychological consequences of such trauma.

PMID- 10065394
TI  - Psychological and physiological characteristics of sweet food "addiction".
AB  - OBJECTIVE: Drug addicts in general can be distinguished from nonaddicts by their
      affective and physiological and craving responses to drug-related cues. The
      purpose of this study was to examine similar affective, physiological, and
      behavioral variables in chocolate "addicts" and control subjects. METHODS:
      Sixteen addicts and 15 control subjects took part in two laboratory experiments
      in which their heart rate, salivation, and self-reported responses were measured.
      RESULTS: In the presence of external chocolate cues, chocolate addicts were more
      aroused, reported greater cravings, experienced more negative affect, and also
      ate more chocolate than control subjects. Self-report measures on eating
      attitudes and behavior, body image, and depression confirmed that a relationship
      exists between "chocolate addiction" and problem eating. Chocolate addicts showed
      more aberrant eating behaviors and attitudes than controls, and were also
      significantly more depressed. DISCUSSION: Chocolate addicts may be considered to
      be a parallel with addicts generally, because they differ from controls in
      craving for chocolate, eating behavior, and psychopathology (in respect of eating
      and affect).

PMID- 10065395
TI  - Anorexia nervosa: friend or foe?
AB  - OBJECTIVE: The aim of this study was to examine anorexics' attitudes towards
      anorexia nervosa. METHOD: Anorexic patients were asked to write two letters to
      their anorexia nervosa, one addressing it as a friend and the other addressing it
      as an enemy. A coding scheme was developed using a "Grounded Theory" methodology
      to group recurrent themes. The scheme was used independently by three raters: the
      first author, a rater with extensive experience in eating disorders, and a novice
      in the field. Use of the coding scheme showed high interrater reliability and
      comprehensivess. RESULTS: Commonly expressed benefits of anorexia nervosa
      included feeling looked after or protected, gaining a sense of control, and
      feeling special. Perceived costs of the disorder included constant thoughts about
      food, feeling taken over, and the damage done to personal relationships.
      DISCUSSION: The positive themes found in the letters are important indicators of
      factors which may maintain anorexia nervosa. The use of the letters to examine
      these factors has important clinical implications which are outlined.

PMID- 10065396
TI  - Elevated plasma lipids in patients with binge eating disorders are found only in
      those who are anorexic.
AB  - OBJECTIVE: We have previously shown that patients with restricting type anorexia
      nervosa (AN-R) have low plasma lipid levels, which increase with refeeding. In
      this study, we investigated plasma lipid levels in patients with eating
      disorders, distinguishing between individuals with bulimia nervosa (BN) and
      anorexia nervosa of the binge eating/purging type (AN-B). METHODS: We examined
      the fasting lipid levels in individuals with BN (n = 10) and AN-B (n = 9), and
      compared these findings with a group of age-matched normal weight healthy
      controls (C) (n = 10). RESULTS: The AN-B group had significantly higher
      concentrations of total plasma cholesterol, apolipoprotein (apo) B, apoA1, and
      low-density lipoprotein (LDL)-cholesterol than both control and BN groups (p <
      .05). The AN-B group also had higher plasma triglycerides and intermediate
      density lipoprotein (IDL)-apo B levels (p < .05) than controls. DISCUSSION: In
      conclusion, the issue of hyperlipidemia in patients with eating disorders is a
      complex one and this study, taken together with the findings of our previous
      study, demonstrates the importance of carefully distinguishing between the major
      types of eating disorders (AN-R, BN, and AN-B) when examining plasma lipid
      levels.

PMID- 10065397
TI  - Development and evaluation of the McKnight Risk Factor Survey for assessing
      potential risk and protective factors for disordered eating in preadolescent and
      adolescent girls.
AB  - OBJECTIVE: To describe the development, test-retest reliability, internal
      consistency, and convergent validity of the McKnight Risk Factor Survey-III (MRFS
      III). The MRFS-III was designed to assess a number of potential risk and
      protective factors for the development of disordered eating in preadolescent and
      adolescent girls. METHOD: Several versions of the MRFS were pilot tested before
      the MRFS-III was administered to a sample of 651 4th through 12th- grade girls to
      establish its psychometric properties. RESULTS: Most of the test-retest
      reliability coefficients of individual items on the MRFS-III were r > .40. Alpha
      coefficients for each risk and protective factor domain on the MRFS-III were also
      computed. The majority of these coefficients were r > .60. High convergent
      validity coefficients were obtained for specific items on the MRFS-III and
      measures of self-esteem (Rosenberg Self-Esteem Scale) and weight concerns (Weight
      Concerns Scale). CONCLUSIONS: The test-retest reliability, internal consistency,
      and convergent validity of the MRFS-III suggest that it is a useful new
      instrument to assess potential risk and protective factors for the development of
      disordered eating in preadolescent and adolescent girls.

PMID- 10065398
TI  - Differences between binge eating disorder and nonpurging bulimia nervosa.
AB  - OBJECTIVE: To compare the pathway to binge eating and clinical characteristics of
      binge eating disorder patients (BED) and nonpurging bulimics. METHODS: The
      subjects were 45 nonpurging bulimics and 45 BED patients who consecutively sought
      treatment in an outpatient eating disorders unit. The subjects underwent a
      clinical interview and replied to the Eating Disorders Inventory and the Hopkins
      Symptom Checklist. RESULTS: In most of the nonpurging bulimics (89%), binge
      eating is preceded by dieting and weight loss, whereas among BED patients the
      pathway to binge eating is more variable. Previous episodes of anorexia nervosa
      are significantly more frequent among nonpurging bulimics than among BED
      patients. The two groups did not differ in other clinical and psychological
      characteristics, such as psychiatric symptoms, frequency of binging, and
      impulsivity traits. However, on many of the variables, the BED group shows a
      significantly greater variance. DISCUSSION: Unlike nonpurging bulimics, BED
      patients appear to form a more heterogeneous group.

PMID- 10065399
TI  - Chest pain in anorexia nervosa.
AB  - OBJECTIVE: To determine the incidence and characteristics of chest pain in
      patients with anorexia nervosa. METHOD: A cross-sectional survey of 54 patients.
      A pain history according to a diagnostic algorithm that was constructed from a
      Medline search (1966-1996) was used. RESULTS: Eighty-seven percent of patients
      had experienced chest pain. The most common diagnosis was idiopathic, occurring
      in 38% of participants. The incidence of typical and atypical angina was 11% and
      9%, respectively. Increasing age, smoking history, and a family history of chest
      pain were more common in those with the atypical or typical angina. CONCLUSIONS:
      Chest pain is a common symptom in patients with eating disorders, and the
      incidence of typical and atypical angina is surprisingly high. All patients with
      eating disorders should be screened for chest pain and other risk factors for
      coronary heart disease.

PMID- 10065400
TI  - The effects of the ideal of female beauty on mood and body satisfaction.
AB  - OBJECTIVE: The present study examined changes in women's mood states resulting
      from their viewing pictures in fashion magazines of models who represent a thin
      ideal. METHOD: Female university students completed the Profile of Mood States
      (POMS), the Body Parts Satisfaction Scale (BPSS), and the Eating Disorder
      Inventory (EDI). They were then exposed to 20 slides; the experimental group (N =
      51) viewed images of female fashion models and a control group (N = 67) viewed
      slides containing no human figures. All subjects then completed the POMS and the
      BPSS again. RESULTS: Women were more depressed (R2 = 0.745, p < .05) and more
      angry (R2 = 0.73, p < .01) following exposure to slides of female fashion models.
      DISCUSSION: Viewing images of female fashion models had an immediate negative
      effect on women's mood. This study, therefore, supports the hypothesis that media
      images do play a role in disordered eating.

PMID- 10065401
TI  - Measuring self-esteem in dieting disordered patients: the validity of the
      Rosenberg and Coopersmith contrasted.
AB  - OBJECTIVE: In order to ascertain the most appropriate measure of self-esteem for
      dieting disordered patients, this study contrasted the construct and convergent
      validities of two widely used measures. In addition, dieting disordered subgroups
      were compared on levels of self-esteem. METHOD: One hundred and seventeen male
      and female patients diagnosed with anorexia nervosa, bulimia nervosa, or eating
      disorder not otherwise specified completed the Rosenberg Self-Esteem Scale (SES),
      the Coopersmith Self-Esteem Inventory (SEI), and measures of dieting disorder
      pathology and depression. RESULTS: No significant differences among the three
      dieting disorder subgroups were found. In determining convergent validity,
      regression analyses indicated that the SES was a significant predictor of dieting
      disorder psychopathology whereas the SEI was not. Of the two self-esteem
      measures, only the SES showed evidence of convergent validity. DISCUSSION: The
      results suggest that the SES has sounder construct and convergent validity than
      the SEI. Hence, the SES may be more appropriate for use with dieting disordered
      populations.

PMID- 10065402
TI  - Methylphenidate treatment for bulimia nervosa associated with a cluster B
      personality disorder.
AB  - OBJECTIVES: Psychotherapy and antidepressant medication are helpful to many
      patients with bulimia nervosa (BN). However, a substantial number of bulimics
      respond poorly to such treatments. Recent studies suggest that many of the poor
      responders have cluster B personality disorders. In some ways, the symptomatology
      of bulimics who have a comorbid cluster B disorder resembles that of patients
      with attention deficit hyperactivity disorder (ADHD). In particular, individuals
      in both groups frequently have a high level of impulsivity. Such a resemblance
      raised the question of whether administration of methylphenidate (MPH), a drug
      used to treat ADHD, would have therapeutic effects in this subgroup of BN
      patients. METHODS: In a pilot study, we administered MPH to 2 patients with BN
      and cluster B traits and found beneficial effects. These patients had not
      responded to adequate trials of psychotherapy and selective serotonin reuptake
      inhibitors (SSRIs). RESULTS: MPH treatment was effective. Both Patients had
      decreased binging and purging. DISCUSSION: MPH may be useful for bulimics with
      cluster B personality disorder who respond poorly to conventional treatment.
      Further studies of MPH administration may be worthwhile. Due to the potential
      risks, however, clinical treatment with this agent is not recommended at this
      time.

PMID- 10065403
TI  - Lipophilicity determination of some potential photosystem II inhibitors on
      reversed-phase high-performance thin-layer chromatography.
AB  - The retention characteristics of 25 2-cyano-3-methylthio-3-substituted amine
      acrylates are determined using reversed-phase thin-layer chromatography (RP-TLC)
      with methanol-water mixtures as eluents. The relationship between Rm values and
      partition coefficients (C log P) are established. The Rm values decrease linearly
      with increasing methanol concentration in the eluent. The Rm values extrapolated
      to zero organic modifier concentration (Rm0) in the eluent are highly related to
      C log P. The Rm0 value can be used to evaluate the lipophilicity of this kind of
      compound.

PMID- 10065404
TI  - Separation of urea, uric acid, creatine, and creatinine by micellar
      electrokinetic capillary chromatography with sodium cholate.
AB  - The capillary electrophoretic separation of the four nonprotein nitrogenous
      compounds (NPNs; urea, uric acid, creatine, and creatinine) typically employed in
      clinical and medical settings for the monitoring of renal function is described.
      Successful resolution of these compounds is achieved with the use of a bile salt
      micelle system composed of sodium cholate at phosphate buffer pH 7.4. The elution
      patterns of four NPNs are obtained within 30 min with a voltage of 30 kV. The
      effect of varying the applied voltage, temperature, and the mole ratio of
      phosphate buffer with bile salt surfactant on the migration behavior is also
      examined.

PMID- 10065405
TI  - Extraction and analysis of cosmetic active ingredients from an anti-cellulitis
      transdermal delivery system by high-performance liquid chromatography.
AB  - A new transdermal delivery system that controls cellulitis is evaluated using
      reversed-phase high-performance liquid chromatography coupled with photodiode
      array detection. An extraction procedure and the validation of the analytical
      method to assay the active excipients from the Centella asiatica plant
      (asiaticoside, madacessic acid, and asiatic acid) are described. Excellent
      results ae obtained in terms of linearity, accuracy, and specificity of the
      analytical method.

PMID- 10065406
TI  - Sharing the dance toward the next century.

PMID- 10065407
TI  - Lipid abnormalities associated with protease inhibitors.
AB  - Treatment for HIV infection in the past 3 years has significantly improved the
      prognosis of people infected with HIV. Protease inhibitors have played a critical
      role in this improved prognosis. Recent findings indicate, however, that protease
      inhibitors may cause significant alterations in lipid metabolism. This study
      reviewed the incidence of lipid abnormalities associated with the use of three
      different protease inhibitor therapies and identified that 56% of those who were
      assessed had abnormal elevated lipids. Following initiation of the protease
      inhibitor, a significant increase in cholesterol was found in 80% of the patients
      on norvir/saquinavir, 51% of patients on indinavir, and 47% of patients on
      nelfinavir. These lipid alterations have added a new and unexpected health risk
      for HIV-infected persons. The risks of therapy with protease inhibitors may have
      a greater life-threatening potential than the disease itself. This article will
      review the published findings suggestive of protease inhibitor hyperlipidemia and
      will highlight the findings of these events in a clinical setting. The purpose of
      this article is to alert the nursing community of this potential serious side
      effects and to make recommendations that may be put into practice so that
      complications may be reduced.

PMID- 10065408
TI  - Hepatitis A and HIV: a clinical review of disease and strategies for prevention.
AB  - Hepatitis A, also known as infectious hepatitis, remains one of the more commonly
      transmitted types of viral hepatitis in the United States. Given the high
      prevalence of this illness, clinicians need to be aware not only about the
      clinical manifestations of this disease, but also about the special
      considerations that must be taken into account for persons coinfected with HIV.
      Antiretroviral management during acute hepatitis infection may be complicated by
      elevations of serum liver enzyme tests as well as by severe manifestations of
      associated symptoms such as nausea and vomiting. This article provides a brief
      overview of the clinical course of HIV infection and includes recommendations for
      antiretroviral medication management during acute illness. Additionally,
      strategies for prevention of disease are presented, with a focus on the efficacy
      and use of hepatitis A vaccines in persons with HIV.

PMID- 10065409
TI  - Quality of life and self-care management strategies of PLWAs with chronic
      diarrhea.
AB  - A case control design was used to examine quality of life and self-care
      management strategies in persons living with AIDS (PLWAs) with chronic diarrhea.
      PLWAs without chronic diarrhea (n = 20) as compared to those with chronic
      diarrhea (n = 20) reported significantly higher general health perceptions (p =
      .028). In contrast, comparisons on symptom status scores revealed that PLWAs
      without chronic diarrhea reported greater fatigue (p = .05), greater
      psychological distress (p = .005), and greater gastrointestinal discomfort (p =
      .01). Although the intensity of chronic diarrhea was reported as moderate to
      severe by 85% of the sample, no single category of self-care management
      strategies was used by more than 65% of respondents. The number of categories of
      self-care management activities was significantly correlated with general health
      perceptions. The study findings support the need to test nursing interventions
      aimed at improving symptom management in chronic diarrhea and facilitating self
      care behaviors including those focused on increasing adherence to prescribed
      therapeutic regimens.

PMID- 10065410
TI  - Nurses decrease barriers to health care by "hyperlinking" multiple-diagnosed
      women living with HIV/AIDS into care.
AB  - The Well-Being Institute (WBI), a community-based nursing organization in
      Detroit, Michigan, has developed and put into practice innovative intervention
      and service delivery models to assist HIV-positive women who have a history of
      substance abuse and mental illness. These multiple-diagnosed women are known to
      have special problems and barriers to accessing health care. The service delivery
      model is based on "hyperlinking" women into hard-to-get health care appointment
      slots through nurses' personal contacts in health care clinics. The intervention
      model is the personalized nursing LIGHT model. This article describes the service
      delivery and intervention models and discusses outcomes of the WBI Women's
      Intervention Program in practice. The program locates HIV-positive, substance
      abusing women; enrolls them in primary medical and mental health care; and helps
      retain them in health care. The results of the model in practice demonstrate its
      success in hyperlinking hard-to-reach and hard-to-serve HIV-positive women with
      health care and other needed services and resources. In addition, these multiple
      diagnosed women have shown positive effects with respect to improved sense of
      well-being and decreased psychosocial distress.

PMID- 10065411
TI  - The expressed needs of a group of HIV-infected gay men subsequent to hospital
      care.
AB  - A qualitative study was conducted to explore how a group of HIV-infected gay men
      experienced their encounters with the health care community and to develop a
      theoretical understanding of the care given from the patient's perspective. Ten
      HIV-infected gay men were recruited from an outpatient clinic in a city in the
      southeastern part of the United States. Collection and analysis of data was
      conducted with a qualitative approach using a constant comparative method. The
      themes summarizing the findings were integration, recognition, security,
      availability of facilities, and confirmation. These themes contain both negative
      and positive experiences and conceptualize different needs from a patient's
      perspective. The role of the nurses' attitudes to and perceptions of gay HIV
      infected men was emphasized.

PMID- 10065412
TI  - Special population: HIV/AIDS among the deaf and hard of hearing.

PMID- 10065413
TI  - Searching for HIV/AIDS information on the World Wide Web.
AB  - Providing patients and their families with information on HIV/AIDS can be a
      challenge given the entire range of tissues that come packaged with the disease
      itself. Information on treatment and resources changes rapidly due to the nature
      of the disease, and it can be difficult to have printed sources on hand that are
      up to date. A greater percentage of patients are now computer literate with
      access to the World Wide Web readily available both at home and in public
      libraries. With this in mind, clinicians should include Web sources when they
      provide information to their patients. With some guidance in choosing among the
      many Web resources available, patients can easily take advantage of this free
      gold mine of information and resources on HIV/AIDS. This article provides a guide
      to choosing among these resources and a list of web sites that can be given to
      patients.

PMID- 10065414
TI  - Thalidomide: the past, present, and future.
AB  - Treatment Review is intended to inform and update nurses about treatments
      relevant to HIV/AIDS. Product information presented in this column does not imply
      endorsement by the Association of Nurses in AIDS Care.

PMID- 10065415
TI  - New CDC guidelines call for TB screening and treatment for all HIV-infected
      individuals.

PMID- 10065416
TI  - Results of simplified screening for Chlamydia in female military recruits suggest
      testing for all sexually active young women.

PMID- 10065417
TI  - New study showed average costs of care for HIV in managed care were lower for
      patients with undetectable viral loads.

PMID- 10065418
TI  - Stress in residency.

PMID- 10065419
TI  - Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial
      growth factor.
AB  - It has been proposed that endothelial cell activation is the primary event in the
      multisystem disorder of preeclampsia. Evidence for endothelial involvement in
      this condition abounds. The best-characterized morphologic abnormality of this
      syndrome, glomerular endotheliosis, involves endothelial cells. Also associated
      with preeclampsia is a loss of endothelial cell integrity, with the consequent
      increase in vascular permeability, and an increase in the circulating levels of
      the endothelial cell markers, fibronectin, von Willebrand factor, tissue
      plasminogen activator, and plasminogen activator inhibitor-1. It is now well
      documented that endothelial activation contributes to the coagulation
      abnormalities observed in this disease. There is much evidence that the
      endothelial alterations in preeclampsia result from one or more circulating
      factors. The incubation of cultured endothelial cells with serum or plasma
      samples, taken from normal pregnant women and women with preeclampsia, results in
      marked alterations in cell behavior and metabolic processes. More recently,
      experiments employing myographic techniques have demonstrated convincingly the
      effects of a circulating factor(s) on the function of endothelial cells of
      resistance arteries. Vascular endothelial growth factor (VEGF) possesses many of
      the characteristics required of a candidate circulating factor. It contains a
      hydrophobic secretory signal sequence, exerts in vitro effects specific to
      vascular endothelial cell, and promotes endothelial expression of procoagulant
      activity. Circulating VEGF concentrations are elevated in women with
      preeclampsia, and VEGF increases microvascular endothelial cell prostacyclin
      production in a dose-dependent manner, analogous to the acute effects of plasma
      from patients with preeclampsia. Similarly, in myographic studies, when
      myometrial resistance arteries are incubated with VEGF, there are dose-dependent
      alterations in endothelium-dependent behavior, mirroring those found after
      incubation with plasma from patients with preeclampsia.

PMID- 10065420
TI  - Relaxation kinetics of the aorta in N omega-nitro-L-arginine methyl ester-treated
      pregnant rats.
AB  - OBJECTIVE: To test the hypothesis that vascular relaxation kinetics are prolonged
      in pregnant rats treated chronically with N omega-nitro-L-arginine methyl ester
      (L-NAME). METHODS: Timed pregnant rats (on day 15 of a 22-day gestation) were
      implanted with infusion pumps containing vehicle (controls) or L-NAME (50 mg/d).
      L-NAME pumps were retained until day 22 (group 1), or removed on day 20 (group
      2). All rats were killed at term. Aortic rings were mounted in organ chambers
      containing physiologic salt solution (PSS) for isometric tension recording,
      contracted with high-K+ PSS (60 mM), and allowed to relax in normal-K+ PSS.
      Relaxation kinetics were quantified as time for 50% and 80% relaxation. After
      contraction with phenylephrine, responses to cumulative concentrations of
      methacholine were studied in the absence and presence of L-arginine (L-Arg) (10(
      3) M). RESULTS: Responses to methacholine were inhibited completely in group 1
      and partially in group 2 (P < .05). The inhibition in both groups was reversed by
      L-Arg. The rate of relaxation was significantly slower in groups 1 and 2 (P <
      .05) as compared with controls. Mechanical removal of the endothelium caused
      prolongation of relaxation in controls and group 2 (P < .05), but not in group 1.
      Preincubation of aortic rings from untreated controls with L-NAME (in vitro, 10(
      4) M) did not affect relaxation. CONCLUSION: The endothelium modulates the rate
      of vascular relaxation by a factor other than nitric oxide. N omega-nitro-L
      arginine methyl ester (L-NAME) prolongs vasorelaxation by endothelium-dependent
      and -independent mechanisms. Prolongation of vascular relaxation kinetics may be
      a mechanism to elevate blood pressure and peripheral vascular resistance in
      preeclampsia.

PMID- 10065421
TI  - Allantoic fluid compositional changes during acute urine drainage in fetal sheep.
AB  - OBJECTIVE: This study examines the effects of ovine fetal urine drainage, which
      prevents urine inflow into the allantoic and amniotic cavities, on allantoic and
      amniotic fluid osmolalities and electrolyte concentrations in an attempt to study
      solute movement out of the allantoic cavity. METHODS: Nine chronically
      catheterized fetal sheep at 132 +/- 2 (mean +/- standard error) [SE] days'
      gestation, with allantoic and amniotic cavity catheters, were studied. Seven
      animals were studied for 9 hours, with maternal and fetal blood drawn hourly, and
      amniotic and allantoic fluid sampled for osmolality and electrolyte
      concentrations. On the second day, seven animals (five from the above group) were
      studied in the same fashion, except that fetal urine was drained after the first
      hour. RESULTS: Allantoic and amniotic fluid osmolality increased significantly
      (13.2 +/- 1.1 (SE) mOsm/kg, P < .0001, 7.5 +/- 1.5, P < .03, respectively) after
      fetal urine drainage but not sufficiently enough to account for the large amount
      of fetal urine diverted (217 mL per 8 hours). Fetal (3.1 +/- 0.6, P < .04) and
      maternal plasma (2.4 +/- 0.5, P < .03) osmolalities increased significantly, and
      this increase was consistent with the amount of fetal urine drained over the 8
      hour drainage period. Allantoic (4.0 +/- 1.7 mEq/L, P < .003) and amniotic sodium
      (4.2 +/- 1.5 mEq/L, P < .03) and amniotic chloride (3.1 +/- 1.6 mEq/L, P < .04)
      increased significantly as compared with control animals. CONCLUSION: During the
      fetal urine drainage period, the increases in allantoic and amniotic fluid
      osmolalities and electrolyte concentrations confirmed that water left these
      compartments via the intramembranous pathway. If only water (and not solutes) had
      left these compartments, then the increase in osmolalities would have been too
      small to account for the large volume of diverted fetal urine. Therefore,
      solutes, in addition to water, must leave the allantoic cavity through the
      intramembranous pathway as no other pathway exists. Furthermore, solute movement
      through the intramembranous pathway may explain the ability of the fetus to
      maintain molecular and solute gradients between fluid compartments. Finally, the
      intramembranous pathway may play an important role in amniotic and allantoic
      fluid volume regulation and composition.

PMID- 10065422
TI  - The acute release of maternal prolactin by instrumental cervical dilatation
      simulates the second stage of labor.
AB  - OBJECTIVE: We hypothesize that artificial stimulation of the cervix causes an
      acute secretion of maternal prolactin (PRL) that mimics PRL secretion during the
      second stage of human labor. METHODS: Eighteen women scheduled for first
      trimester therapeutic abortion had a blood sample drawn at the following times:
      before and after laminaria tent (LT) insertion for cervical ripening, 18-24 hours
      later upon entry in the procedure room, after LT removal, during instrumental
      cervical dilatation and uterine evacuation by suction curretage, soon after
      evacuation, and 1/2 hour and 1 hour after evacuation. Local cervical anesthesia,
      intravenous analgesics, and sedation were administered before the procedure.
      Blood serum was assayed for PRL, human chorionic gonadotropin (hCG), and
      estradiol. RESULTS: The initial PRL levels were 34 ng/mL +/- 4.2 standard error
      of the mean (SEM) and did not change after 18-24 hours of LT placement nor after
      LT removal. However, PRL increased significantly (t = 5.8; P = .00001) over basal
      levels by 204% +/- 15 at the time of instrumental dilatation and rose to 378% +/-
      33 at 1/2 hour postevacuation. After 1 hour, PRL had declined to 173% +/- 10%.
      Serum levels of estradiol and hCG changed only after evacuation. CONCLUSION:
      Artificial stimulation of the cervix causes an immediate surge in PRL levels. We
      suggest that the acute increase in pituitary PRL secretion that occurs during the
      second stage of labor results from a neural signal from the cervix and not from
      endocrine changes associated with labor.

PMID- 10065423
TI  - The effects of sex steroids on human umbilical artery and vein.
AB  - OBJECTIVE: To define the vascular actions of selected sex steroids on human
      umbilical artery and vein and to determine whether there are any gender-specific
      differences in vasorelaxation between umbilical cord vessels of male and female
      fetuses. METHODS: Segments of umbilical artery (n = 12) and umbilical vein (n =
      8) from male and female fetuses were suspended in organ baths of Krebs solution
      for isometric tension recording. The vessels were contracted using 60 mM
      potassium chloride followed by exposure to increasing concentrations (10(-7) to
      10(-4) M) of sex steroid hormones (estradiol-17 beta, estriol, estrone,
      testosterone, and progesterone). A specific estrogen receptor antagonist (ICI
      164, 384) was used to attempt to block the estradiol effect. Changes in tension
      were recorded. RESULTS: Of the agents tested, estradiol-17 beta had the greatest
      effect (25-29% relaxation at 10(-4) M concentration), which was uninhibited by a
      specific receptor antagonist. The other steroids tested had no significant
      effect, even at 10(-4) M concentration. The umbilical artery is slightly more
      sensitive to the effects of estradiol than the umbilical vein. There were no
      gender-specific differences noted in either artery or vein harvested from male or
      female fetuses. CONCLUSION: Estradiol-17 beta in supraphysiologic concentrations
      has a non-receptor-mediated vasorelaxation effect on human umbilical blood
      vessels.

PMID- 10065424
TI  - Genome scanning detects amplification of the cathepsin B gene (CtsB) in
      transformed rat ovarian surface epithelial cells.
AB  - OBJECTIVE: To isolate a portion of the amplicon inferred to be present in a
      malignant rat tumor cell line, NuTu 26, by the presence of a homogeneously
      staining chromosomal region (hsr) and identify genes embedded within it. METHODS:
      Genome scanning was used to identify an EcoRI fragment (8.6 kbp) within the
      amplified region of the NuTu 26 genome using a recently identified rat repetitive
      sequence, OST17 as a probe. The 8.6 kbp amplified fragment was sequenced and used
      as starting material to obtain additional sequence information by screening a P1
      clone-derived DNA library to identify any genes likely embedded in the amplicon.
      Use of the microdissected hsr as a probe for fluorescence in situ hybridization
      (FISH) and application of Southern, Northern, and Western blot analysis confirmed
      the amplification of this region in the NuTu 26 genome. RESULTS: The cathepsin B
      gene was within the amplicon of the hsr-containing marker chromosome of NuTu 26.
      FISH analysis and chromosomal banding further revealed that the marker chromosome
      was a derivative of chromosomes 4 and 15, i.e., der(15)t(4;15). CONCLUSION:
      Cathepsin B gene amplification may contribute to some aspect of the biology of
      ovarian cancer. This concept is strengthened by the finding that the gene is
      overexpressed frequently in independently transformed rat ovarian surface
      epithelial cells.

PMID- 10065425
TI  - Overexpression of macrophage colony-stimulating factor (CSF-1) and its receptor,
      c-fms, in normal ovarian granulosa cells leads to cell proliferation and
      tumorigenesis.
AB  - OBJECTIVE: To investigate the interdependent role of macrophage colony
      stimulating factor (CSF-1) and its receptor (c-fms) on their induction and their
      role in granulosa cell tumorigenesis. METHODS: Normal ovarian granulosa cells
      were used to develop stable transfectants that overexpress CSF-1 or CSF-1/c-fms.
      CSF-1 was expressed under the control of tissue/cell specific alpha-inhibin
      promoter, and c-fms was expressed constitutively using a viral promoter. Stable
      transfectants were used to examine the effect of overexpression of these
      molecules on the proliferation, induction of autocrine loop, and tumorigenesis.
      RESULTS: Expression vectors were developed for CSF-1 and its receptor, c-fms, and
      used to generate stable transfects overexpressing these genes in granulosa cells.
      Data show that overexpression of CSF-1 leads to the induction of its receptor.
      Stable transfectants that overexpress CSF-1 show about a 2.5-fold increase in
      cell proliferation compared with normal granulosa cells, and these cells are also
      converted to anchorage-independent and tumorigenic phenotype. Using an antisense
      RNA approach, we also demonstrated that the increased cell proliferation is CSF-1
      specific. Concomitant overexpression of CSF-1 and c-fms further results in
      increased cell proliferation (sixfold), rapid anchorage-independent growth, and
      aggressive tumor formation. CONCLUSION: CSF-1 is capable of inducing its own
      receptor, and, similarly, the CSF-1 receptor, c-fms, can also induce its growth
      factor ligand. These studies also demonstrate the interdependent role of these
      genes in transformation of normal ovarian granulosa cells to a tumorigenic
      phenotype and suggest the possibility of a similar role for these genes in
      progression of ovarian cancer.

PMID- 10065426
TI  - Reversal of diurnal cortisol rhythm and suppression of plasma testosterone in
      obstetric residents on call.
AB  - OBJECTIVE: The study was undertaken to quantify the psychologic and physiologic
      responses to the stresses of an obstetrics/gynecology residency program. METHODS:
      Six male residents were studied on four occasions: one day during the first 2
      weeks of their residency, one day immediately following a vacation period, one
      day after a night on call in obstetrics, and one day while in the gynecology
      clinic. Stress was evaluated by validated psychologic instruments and by levels
      of plasma testosterone, luteinizing hormone (LH), cortisol, and prolactin in
      morning and afternoon blood samples. RESULTS: Self-reported stress was
      significantly elevated during the first 2 weeks of the residency after a night on
      call. Anxiety scores were significantly elevated after a night on call as were
      depression subscores for some residents. Plasma testosterone was highly
      significantly suppressed after the obstetrics night on call and during the first
      2 weeks of the residency in comparison with the vacation period. Luteinizing
      hormone levels were also significantly lower after the obstetrics on-call
      experience. Plasma cortisol levels after a night on call were suppressed in the
      morning and normal or elevated in the afternoon. In comparison, the gynecology
      rotation was associated with normal levels of testosterone and lower levels of
      cortisol. CONCLUSION: In this small sample of residents, we observed an inverse
      relationship between self-reported stress levels and the concentrations of plasma
      testosterone and LH. The high levels of stress and anxiety expressed after a
      night on call also disrupted the normal pattern of plasma cortisol levels.

PMID- 10065427
TI  - [A risk analysis of congenital defects due to drug intake during pregnancy.
      Spanish Collaborative Study of Congenital Malformations].
AB  - BACKGROUND: Illicit drug abuse is a major area of interest, for clinicians, as
      well as for public health and social authorities. But one of the major concerns
      is the illicit drug abuse during the periconceptional period and throughout
      pregnancy, because of its potential effect on the embryo and fetus. In this study
      we analyze the possible risk of illicit drug abuse during pregnancy for different
      selected congenital defects. MATERIALS AND METHODS: We analyzed the annual
      evolution of the proportion of mothers who are addicted to illicit drugs, as well
      as some of their characteristics. We also performed a case-control study using
      different models of multiple logistic regression analyses, controlling possible
      confounding factors. RESULTS: We observed that the proportion of mothers who are
      addicted to illicit drugs shows an increasing liner trend over time. On the other
      hand, these mothers are younger that those who are not consumers of illicit
      drugs, and have an overall risk for congenital defects of 1.84 (p = 0.007). We
      also studied the different selected types of congenital defects, controlling the
      potential effect of the following variables: maternal age, maternal cultural
      level, maternal alcohol, maternal smoking, and vitamins/minerals during
      pregnancy. In these analyses we obtained statistically significant increased
      risks for: neural tube defects, choanal atresia, esophageal atresia,
      gastroschisis, anal atresia, and postaxial polydactyly. CONCLUSIONS: The women
      who are addicted to illicit drugs during pregnancy, have an increased risk for
      infants with several congenital defects. The way to prevent these effects should
      be based on a good information about this aspect to the general population, as
      well as on a careful medical control of the nutrition of these mothers and their
      health and social conditions during gestation, and the treatment of their
      addiction before and during pregnancy.

PMID- 10065428
TI  - [Fibronectin and diabetes mellitus: the factors that influence its plasma
      concentrations and its usefulness as a marker of late complications].
AB  - BACKGROUND: The usefulness of plasma fibronectin (FNp) as a marker of late
      diabetic complications is controversial. The aim of the study was to assess the
      influence of several variables on FNp in diabetic patients and to determine its
      usefulness as a marker of late diabetic complications. PATIENTS AND METHODS: 79
      diabetic patients randomly selected were included in the study. The clinical
      variables considered were: age, gender, body mass index (BMI), tobacco and
      alcohol consumption, type, duration and treatment of diabetes, hypertension, and
      diabetic late complications (macroangiopathy, retinopathy, nephropathy and
      neuropathy). The laboratory variables analyzed were: blood glucose, glycated
      hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, tryglicerides,
      apolipoprotein AI, apolipoprotein B, microalbuminuria, creatinin and FNp.
      Statistical study included a multiple regression analysis taking FNp as the
      dependent variable. RESULTS: A direct correlation between FNp and BMI and also
      with tryglicerides was observed (r = 0.362; p = 0.002, and r = 0.234; p = 0.038,
      respectively). Higher levels of FNp were found in type 2 diabetic patients in
      comparison with type 1 (464 [SD, 127] versus 395 [SD, 96] mg/dl; p = 0.014). This
      difference was due to the higher BMI and tryglicerides concentrations observed in
      type 2 diabetic patients in comparison with type 1 (28.61 [SD, 4.67] versus 22.56
      [SD, 2,.19] kg/m2; p < 0.001, and 4.24 [SD, 2.36] versus 2.52 [SD, 1.40] mmol/l,
      respectively). Multiple regression analysis showed that only BMI significantly
      influenced on FNp concentrations (r = 0.330; p = 0.004). No relation among FNp
      and late diabetic complications and other variables considered in the study was
      observed. CONCLUSIONS: FNp is not a useful marker of diabetic late complications
      and its concentrations are direct and independently influenced by BMI.

PMID- 10065429
TI  - [Mutations in the BRCA1 gene in young Spanish women with breast cancer].
AB  - BACKGROUND: Germline mutations in the BRCA1 gene have been associated with
      familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset
      breast cancer have a higher probability of being carriers of BRCA1 mutations. Our
      aim was to know prevalence of BRCA1 mutations in women with breast cancer
      diagnosed before 40 years. PATIENTS AND METHODS: We analyzed genomic DNA samples
      of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering
      the 36% of cases with mutations described in the literature were screened.
      Analysis involved polymerase chain reaction (PCR), single-strand conformation
      polymorphisms (SSCP) and direct sequencing. RESULTS: Three germline BRCA1
      mutations were identified, one of them not previously described. Two mutations
      were found in women with familial history of breast cancer. Five additional rare
      variants and polymorphisms were also detected. CONCLUSIONS: The absence of
      recurrent mutations or mutations detected in other countries, except for the
      185delAG mutation, present in Ashkenazim population, shows the influence of
      ethnic and geographic origin of population studied, and illustrates the
      difficulties of establishing DNA-based screening tests for hereditary breast
      cancer.

PMID- 10065430
TI  - [Adverse drug reactions in the Spanish medical bibliographic literature: a
      comparison of 3 periods].
AB  - BACKGROUND: A quantitative and qualitative assessment of reports on suspected
      adverse drug reactions (ARD) in Spanish medical literature was carried out.
      MATERIALS AND METHODS: The periods analysed were 1972-1974, 1986-1988 and 1992
      1994, and the medical journals were Anales de Medicina Interna, Medicina Clinica
      and Revista Clinica Espanola. We selected all articles including specific
      information on suspect ADR. RESULTS: The percentage of articles has increased
      considerably (1972-1974: 2.1%, 1986-1988: 5.7%, and 1992-1994: 8.2%). In spite of
      this growth, the qualitative data studied have not significantly improved.
      CONCLUSIONS: It is necessary to device some mechanism in order to improve ADR
      reporting.

PMID- 10065431
TI  - [Congenital defects and drugs of noninstitutional use].

PMID- 10065432
TI  - [Will it be possible to treat atherosclerosis with antibiotics?].

PMID- 10065433
TI  - [The SAPHO syndrome: a study of 16 cases].
AB  - The SAPHO syndrome is characterized by synovitis, acne, palmo-plantar pustulosis,
      hyperostosis and osteitis. SAPHO syndrome has been occasionally described in
      Spain. We present our experience of 16 cases with the SAPHO syndrome diagnosed
      between 1984-1995. The predominant clinical symptoms were: anterior thoracic pain
      (14 cases), sacroiliac pain (7 cases) and peripheral arthritis (2 cases).
      Cutaneous involvement was characterized by palmo-plantar pustulosis (8 cases)
      acne (3 cases) and psoriasis (2 cases). The histocompatibility antigen B27 was
      negative in all cases. A computerized tomographic study revealed involvement of
      sterno-costo-clavicular and manubriosternal joints (14 cases) and sacroiliitis (8
      cases).

PMID- 10065434
TI  - [Ethics versus bioethics].

PMID- 10065435
TI  - [Hormonal substances used as ergogenic agents].

PMID- 10065436
TI  - [Boane, Odet and Antony with an Ethiopian ending. The risks and obligations of
      our intervention].

PMID- 10065437
TI  - [A comparison of the results of cytogenetic studies in de novo and secondary
      acute myeloblastic leukemias. A study of 69 patients].

PMID- 10065438
TI  - [The inappropriate antidiuretic hormone secretion syndrome and citalopram].

PMID- 10065439
TI  - [Persistent pancreatic involvement in malathion poisoning].

PMID- 10065440
TI  - [Sepsis due to DF2].

PMID- 10065441
TI  - [The Eaton-Lambert myasthenic syndrome and subacute cerebellar degeneration of a
      nonparaneoplastic origin: a review of a case 4 years later].

PMID- 10065442
TI  - [Molecular biology and cerebrovascular diseases].

PMID- 10065443
TI  - [Proliferation inhibition of glioma cells by vitamin K2].
AB  - The antitumor effects of vitamin K2 were studied using three glioma cell lines:
      C6 (rat glioma cell), RBR17T and T98G (human glioma cell). The antitumor effects
      were estimated by count assay. The results was that vitamin K2 induced growth
      inhibition in a dose-dependent manner. The RBR 17T cells exposed to vitamin K2
      for 72 hours resulted in oligonucleosomal DNA fragmentation and formed a ladder
      on agarose gel electrophoresis. Furthermore, the RBR17T cells exposed to vitamin
      K2 for 24 hours were significantly accumulated in the G0G1 phase of the cell
      cycle. Those results suggested that vitamin K2 can inhibit the proliferation of
      cells through the induction of cell cycle arrest and apoptosis for tumor cells.
      The combined treatment of vitamin K2 with ACNU or 5-FU or INF-beta or 1,25
      dihydroxyvitamin D3 enhanced growth inhibition significantly. In conclusion,
      vitamin K2 can be a useful drug for the treatment of glioma.

PMID- 10065444
TI  - [A clinical analysis of patients with primary intracranial germinomas: the
      relationship between proliferative potential and recurrence].
AB  - We analyzed clinically 30 germinomas (22 pure germinomas and 8 germinomas with
      syncytiotrophoblastic giant cell (STGC) and also investigated the proliferative
      potential of 18 germinomas immunohistochemically using MIB-1 monoclonal antibody
      in formalin-fixed paraffin-embedded sections. The majority of patients responded
      favorably and completely to the treatment. Seven patients (four had germinomas
      with STGC and the other three had pure germinomas) suffered recurrence after a
      complete response to radiotherapy and/or chemotherapy. The patients with
      germinomas with STGC experienced recurrence significantly more often than those
      with pure germinomas (P < 0.01). Three of the patients died. The MIB-1 indexes of
      the germinomas ranged from 18% to 80%. The average MIB-1 index of pure germinomas
      is 58.5 +/- 17.3%, that of germinomas with STGC is 45.3 +/- 17.1%. There was no
      significant difference between the two groups. The MIB-1 indexes of 3 recurrent
      cases were 64.3%, 51.9%, and 20.8%, respectively. There were no significant
      differences in the MIB-1 indexes between nonrecurrent cases and recurrent ones.

PMID- 10065445
TI  - [Percutaneous dilational tracheostomy: report of 9 cases].
AB  - Nine patients with CNS damage who had been transferred to our critical care unit
      were treated with a commercially available kit for percutaneous dilational
      tracheostomy (PDT). The mean procedure time was about 11 minutes, and the
      perioperative complication rate was 22% (2/9). Only one complication, wound
      infection, occurred, and the patient was cured with conventional therapy. On the
      other hand, premature extubation of the translaryngeal tube occurred in one case.
      Long-term complications like tracheal stenosis and tracheal malacia were not
      experienced in two patients. They were discharged from the hospital after
      decannulation. In conclusion, the advantages of PDT include a short procedure
      time, the ability to perform the procedure at the bedside, and reduced
      stimulation of the trachea. Because of the safety and simplicity of the
      procedure, we recommend PDT for patients with CNS damage.

PMID- 10065446
TI  - [Clinical results of supratentorial astrocytoma grade II].
AB  - At present, there is no consensus concerning the treatment of low-grade gliomas.
      The authors conducted a retrospective review of surgically treated,
      histologically verified cases of supratentorial astrocytomas of grade II to
      evaluate the results of current treatment methods. Thirty-seven patients, 23
      males and 14 females, treated from April, 1977 through March, 1997 were analyzed.
      Median patient age was 36 years (range 2-69 years). All patients were diagnosed
      by surgical specimens. Thirty were fibrillary, and three were gemistocytic
      astrocytomas. There were 13 total resections, 7 subtotal resections, 10 partial
      resections. Of the remaining 7, diagnosis was obtained by stereotactic biopsy.
      Twenty patients were irradiated and two received chemotherapy. Follow-up
      information was obtained for 33 patients. The follow-up time ranged from 4 months
      to 246 months (mean, 9 years). Overall survival rates at 5 and 10 years for the
      entire treated group were 71% and 57% respectively. Total and subtotal resections
      were significantly associated with longer survival time, the 5- and 10-year
      survival rates were 93% and 67%, respectively. They were 40% and 40% in patients
      with partial resection or needle biopsy. Patients with gemistocytic astrocytoma
      had a poor prognosis with a median survival of 44.5 months. The influence of
      radiotherapy was not obvious: 92 and 69% of patients were alive at 5 and 10 years
      respectively without radiotherapy. The extent of surgery and histological type
      were by far the most important factors in predicting length of survival. The
      importance of an accurate histologic diagnosis and a gross total resection is
      emphasized.

PMID- 10065447
TI  - [Endovascular treatment of ruptured intracranial aneurysms using platinum coils
      in patients over 80 years of age].
AB  - Endovascular treatment of intracranial aneurysms using plantinum coils was
      performed in 10 patients over 80 years of age. The patients ranged in age from 81
      to 96 years. Preoperative Hunt and Kosnik grading revealed one patient in grade
      I, 4 in grade II, 3 in grade III, and 2 in grade IV. The aneurysms were located
      in the internal carotid artery in 6 patients, in the anterior communicating
      artery in 1, and in the middle cerebral artery in 3 respectively. Intra
      aneurysmal occlusion was accomplished in 8 patients with total or subtotal
      occlusion in 6 and partial occlusion in 2. In one patient with a peripheral
      middle cerebral artery aneurysm, the parent artery was occluded just proximal to
      the aneurysm. In the remaining one patient in grade III, an aneurysm associated
      with wide neck could not be occluded because of coil protrusion into the parent
      artery. In 9 patients who were successfully treated, all five patients in grade I
      or II and one in grade III resulted in good outcome, but the other three patients
      in grade III and IV showed poor outcome. No evidence of recurrent hemorrhage was
      noted during the follow-up period ranging from 2 months to 4 years. Endovascular
      coil embolization is a useful therapeutic alternative for treating ruptured
      intracranial aneurysms in patients over 80 years of age, especially those in
      Grade I or II.

PMID- 10065448
TI  - [Extravasation of contrast media in acute subdural hematoma during three
      dimensional CT angiography: a case report].
AB  - We report a case of acute subdural hematoma in which extravasation of contrast
      medium was demonstrated using three-dimensional computed tomographic angiography
      (3D-CTA). An 83-year-old man was found lying down on the floor but he was
      conscious. Thirty minutes later, he lost consciousness and was transferred to our
      hospital in a comatose state with right hemiparesis. Plain CT scan showed a left
      temporoparietal acute subdural hematoma with subarachnoid hemorrhage. CT scan
      also demonstrated an iso-density area beneath a high-density around the left
      Sylvian fissure. We performed an emergent 3D-CTA to rule out ruptured aneurysm as
      the cause of hemorrhage. However, 3D-CTA revealed no cerebral aneurysm, but
      extravasation of contrast medium from the cortical artery of the left temporal
      cortex was noted. The patient immediately underwent total evacuation of subdural
      hematoma by small temporoparietal craniectomy under local anesthesia. We found 3D
      CTA to be a useful, less-invasive method for diagnosing the hemorrhagic cause and
      localizing the bleeding point. It is expected that with more routine use of 3D
      CTA in patients with acute subdural hematoma, extravasation of the contrast
      medium will be seen more frequently. Subdural hematoma with extravasation of
      contrast medium required emergent surgery, and 3D-CTA findings facilitated the
      selection of the surgical method according to the bleeding point.

PMID- 10065449
TI  - [Cranial fasciitis of a neonatal case with massive intra- and extracranial
      extension].
AB  - We report a neonatal male case of cranial fasciitis in childhood. He was born
      with a large skull tumor in his left fronto-parietal region. The day after his
      birth, he was admitted to our hospital. On inspection, the mass was firm, non
      mobile, and had two humped peaks. The size of the mass was 7 x 5 x 4 cm, and it
      was located on the left coronal suture and fontanelle. The overlying skin was
      normal. Skull X-rays revealed osteolytic defect and linear bone remnant skirted
      the outer rim of the tumor. CT scan showed a slightly high-density large frontal
      mass with a low density area in the center of it and marked enhancement. MR
      images revealed a large mass with massive intra- and extracranial extension.
      Cerebral angiography showed the remarkable vascularization of the tumor.
      Preoperatively, the branches of the external carotid artery were partly
      embolized. On surgery, the profusely bleeding, elastic hard, yellowish-white mass
      arising from the dura was partially removed with the surrounding bone. A small
      mass remained subdurally. The boundary of the mass and the dura was not well
      demarcated. After the operation, no neurological deficits were seen. 16 months
      after the surgery, MRI revealed the unfolded brain with no evidence of tumor.
      Histological examination showed characteristic proliferation of spindle-shaped
      fibroblasts embedded in a collagenous stroma. Inflammatory lymphocytes and
      acidophils were also noted. Electron micrograph revealed a tumor cell rich in
      rough endoplasmic reticulum and nuclei with numerous indentations. Immunostaining
      confirmed that these cells were positive for vimentin but negative for smooth
      muscle actin, GFAP, S-100 protein, and desmin. No recurrence of this tumor has
      been detected at four years of follow-up.

PMID- 10065450
TI  - [Two cases of facial neurinoma successfully treated with gamma knife
      radiosurgery].
AB  - Two cases of facial neurinoma successfully treated with gamma knife radiosurgery
      are reported. Case 1, a 33-year-old female, developed a right-sided hemifacial
      spasm about five years ago. Then she suffered gradual progression of right-sided
      facial palsy, dysgeusia and reduction of lacrimation, but she had no hearing
      disturbance. T1-weighted MRI with gadolinium DTPA showed a well-circumscribed
      tumor at the geniculate ganglion extending to the middle cranial fossa. The tumor
      was treated with gamma knife radiosurgery which reduced its size, but didn't
      reduce the patient's facial palsy. Case 2, a 36-year-old female, presented with
      fluctuating facial palsy and sensorineural hearing loss lasting for fourteen
      years. T1-weighted enhanced MRI showed a well-enhanced tumor at the CP angle
      extending to the middle cranial fossa. The tumor was treated with gamma knife
      radiosurgery, which caused central tumor necrosis, but didn't reduce the tumor
      size. Meanwhile the patient's facial palsy improved. Gamma knife radiosurgery is
      apparently effective against facial neurinomas without producing serious
      complications such as complete facial palsy and hearing loss. Our study indicates
      that gamma knife radiosurgery is a useful therapeutic alternative for facial
      neurinomas.

PMID- 10065451
TI  - [Multiple aneurysms of the PICA communicating artery: a case report].
AB  - A case with unusual type of aneurysms in the distal posterior inferior cerebellar
      artery (PICA) is reported here. Though only two cases with a single aneurysm of
      the PICA communicating artery have been reported previously, the present case is
      the first one with multiple aneurysms in the PICA communicating artery. A 61-year
      old woman with a sudden onset of severe headache, vomiting and unconsciousness
      was transferred to our hospital. CT scan revealed a hematoma in the fourth,
      third, and lateral ventricles, and a mild subarachnoid hemorrhage at the
      posterior fossa. Cerebral angiogram showed the right PICA supplying the
      hypoplastic left PICA territory through an anastomotic vessel. Two small
      aneurysms were seen at the tips of hairpin curves of an anastomotic vessel, "the
      PICA communicating artery". Suboccipital craniotomy was performed, and the
      ruptured aneurysm was clipped and the unruptured one was wrapped with cotton
      sheet. After the operation, her clinical recovery went well and she was
      discharged on foot.

PMID- 10065452
TI  - [Emergency stenting for iatrogenic occlusion of internal carotid artery during
      percutaneous transluminal angioplasty: a case report].
AB  - The authors report the case of a 68-year-old male who underwent emergency
      stenting for iatrogenic occlusion of the internal carotid artery while he was
      receiving percutaneous transluminal angioplasty. He presented with a 1-month
      history of transient ischemic attacks with right-sided hemiparesis. Carotid
      angiography revealed a 95% eccentric stenosis at the origin of the left internal
      carotid artery. As the stenotic lesion was higher than the level of the third
      cervical vertebral body, percutaneous transluminal angioplasty was performed
      instead of carotid endarterectomy. During the procedure, the left internal
      carotid artery was dissected, then obstructed completely with rapid deterioration
      of his neurological condition. The Palmaz-Schatz stent was successfully deployed
      over the site of dissection to restore normal patency through the dissected
      carotid artery. Following emergency stenting, his neurological signs quickly
      subsided. Since then, with oral administration of antiplatelet medication, he has
      suffered no recurrence of cerebral ischemic events. Echo-ultrasonography 4 months
      after stent implantation showed good patency of the stented segment. It has been
      reported that angioplasty is indicated for high-risk patients or surgically
      inaccessible lesions in stenotic disorders of the internal carotid artery.
      However, there are several complications reported, including intimal dissection
      and restenosis. The present case emphasizes the usefulness of emergency stenting
      when occlusion of the internal carotid artery is complicated during percutaneous
      transluminal angioplasty.

PMID- 10065453
TI  - [Unilateral visual field defect due to optic nerve compression by sclerotic
      internal carotid artery: a case report].
AB  - A case of unilateral visual field defect due to optic nerve compression by a
      sclerotic internal carotid artery was reported. A 71-year-old woman was admitted
      to our department because of constricted visual field of the right eye. MRI
      showed elevation of the right optic nerve compressed by an internal carotid
      artery. The right carotid angiography revealed elevation and distortion of the C1
      2 portion. Frontal craniotomy was carried out and the optic nerve was visualized
      on this side. The right optic nerve was found to have been compressed by the
      sclerotic internal carotid artery. The optic canal was then unroofed. The post
      operative course was uneventful. The visual field was improved. When last seen 6
      months after surgery, her visual field remained in the improved condition. Nasal
      field abnormalities are most frequently encountered in retinal and anterior optic
      nerve pathology. Our success in improving the visual field disturbance may be
      accounted for by the fact that the preoperative period was short and the
      operation was performed before atrophy of ocular fundi occurred. Nasal field loss
      caused by intracranial lesions of the optic pathway is rare. It is probably
      impossible to determine degree of the symptomatology caused by direct-pressure
      compression as opposed to that caused by ischemia secondary to occlusion of small
      arterial supply branches. Vascular compressive neuropathy of optic nerve should
      not be diagnosed simply by the radiological finding of the optic nerve
      dislocation. However, optic nerve compression by surrounding arteries should be
      remembered as one of the possible causes of visual field defect which needs to be
      treated surgically.

PMID- 10065454
TI  - [Ketamine infusion therapy for refractory neuralgia in spinal disease: report of
      two cases].
AB  - We report two cases of refractory pain in a spinal disease. One case was a 60
      year-old male who presented intractable pain in bilateral upper extremities after
      anterior fusion (C5/6, 6/7) for cervical spondylosis. The other was a 63-year-old
      female who also had intractable pain in the left anterio-lateral chest wall with
      no remarkable past history. Both cases were refractory to nonsteroidal anti
      inflammatory drugs (NSAIDs) or minor tranquilizer or local anesthesia with
      bupivacaine. However, their pain was significantly relieved by the intravenous
      administration of a test dose (5mg) of ketamine which is a noncompetitive blocker
      of N-methyl-D-aspartate (NMDA) receptors. As for case 1, the effect of the
      injection of the test dose lasted, so continuing infusion therapy of ketamine was
      cancelled. In case 2, recurrence of the pain was recognized gradually. She
      underwent continuing infusion therapy of 2mg/kg of ketamine, and it brought about
      continued pain relief. We conclude that ketamine infusion therapy should also be
      considered for therapy of refractory neuralgia in spinal disease.

PMID- 10065456
TI  - [Tuberous sclerosis].

PMID- 10065455
TI  - [Phacomatosis].

PMID- 10065457
TI  - [Neurofibromatosis].

PMID- 10065458
TI  - [von Hippel-Lindau disease].

PMID- 10065459
TI  - [The spinal somatosensory evoked potentials in amyotrophic lateral sclerosis in
      relation to the spinal cord conduction velocities].
AB  - The lumbar-to-cervical conduction velocity (spinal cord conduction velocity,
      SCCV) was electrophysiologically studied in 14 patients with amyotrophic lateral
      sclerosis (ALS). The age of these patients ranged from 37 to 63, averaging 51.0
      years old. We recorded the spinal somatosensory evoked potentials (SSEPs) from
      the surface electrodes at the level of the C2 spine and the T12 spine by the
      simultaneous stimulation of bilateral posterior tibial nerves. SCCV from the
      lumbar to cervical was measured from the latency difference between both SSEPs
      elicited at the each position. As the results, SCCVs were in the range of 50.6
      66.6 (58.6 +/- 4.7: mean +/- SD) m/sec in normal age matched controls (18 adult
      volunteers, 46-63 years old, averaging, 52.7). On the other hand, in ALS
      patients, SCCVs were in the range of 42.1-67.1 (53.5 +/- 7.8: mean +/- SD) m/sec,
      values of which were lowered compared to those in normal subjects. These
      examination documented 4 out of 14 patients with ALS (28.6%) showing
      abnormalities beyond standard deviation. The vibration sense was checked by using
      128 Hz tuning fork at the ankles, and for the quantitative measurement, a newly
      designed vibriometer being attached the piezoelectric accelerometer to the end of
      128 Hz tuning fork was applied in 14 ALS patients. The vibration sense at the
      ankles was diminished in 6 patients, and 3 patients showed the abnormalities
      beyond 2 standard deviations. The degree of lowering in SCCVs among ALS patients
      were correlated with the degree of diminution of impaired vibration sense and the
      duration of illness, but were not correlated with the H/M ratio and the latency
      difference between T wave and H wave. Since SSEP impulses are transmitted in
      dorsal columns and dorsolateral fasciculus predominantly by large diameter and
      fast-conduction fibers, our results may suggest that, in ALS patients, spinal
      cord conduction velocities of ascending fibers mediating the dorsal columns and
      dorsolateral fasciculus are disturbed compared to those in normal subjects, and
      that the functional disturbance of ascending fibers mediating the dorsal columns
      and dorsolateral fasciculus plays the important role in the high rates of
      impaired vibration sense among ALS patients.

PMID- 10065460
TI  - [Ibudilast prevents oxygen-glucose deprivation-induced oligodendroglial injury].
AB  - Previously we have demonstrated that ibudilast, which is used clinically for
      treating patients with asthma and cerebrovascular diseases, prevents
      excitotoxicity of oligodendroglial lineage mediated by Ca2+ influx via non-N
      methyl-D-aspartate (NMDA) glutamate receptor (GluR) channels. We here present a
      finding that ibudilast prevents oxygen-glucose deprivation (OGD)-induced
      oligodendroglial injury. The oligodendrocyte-like cells (OLC), differentiated
      from the CG-4 cell line established from rat oligodendrocyte-type-2 astrocyte (O
      2A) progenitor cells, were exposed to hypoxia in the absence of glucose for 12 h
      and subsequent reoxygenation for 2 h. Cell damage was evaluated by measuring
      activity of lactate dehydrogenase (LDH) released into the culture medium. OGD for
      12 h induced 30 to 50% LDH release into the medium. OLC damage induced by
      deprivation of oxygen and glucose was prevented by ibudilast at concentrations of
      > or = 50 microM. The protection given by ibudilast against OGD-induced injury
      was enhanced by prostacyclin (PGI2). OGD-induced OLC injury was prevented by 6
      cyano-7-nitroquinoxaline-2, 3-dione (CNQX), an inhibitor of non-NMDA GluR or
      deprivation of Ca2+ from culture medium. While ibudilast increased intracellular
      cAMP at concentrations of > or = 10 microM, at least 100 microM concentrations
      were needed to increase intracellular cGMP. Therefore, we concluded that
      ibudilast prevented OGD-induced oligodendroglial injury possibly by increasing
      intracellular cAMP which modulates Ca2+ influx via non-NMDA GluR channels.

PMID- 10065461
TI  - [A case of post-traumatic autobiographic amnesia].
AB  - A 23-year-old woman who was in the ninth month of pregnancy suffered a head
      injury by falling from the stairs. She regained consciousness in the ambulance
      car, however, could not recall anything about herself. The morning after, her
      neurological examination disclosed no abnormal findings. She was alert, spatially
      oriented, but unable to recall any personal information about herself, her work
      and family contexts. The results of WAIS-R and WMS were within normal range, and
      she showed a dissociation between a detailed knowledge of public events and
      famous people and a complete loss of autobiographic information. EEG and brain
      MRI were normal. Memory loss spontaneously recovered following several months,
      and 8 month later, the retrograde amnesia had almost resolved. Although it is
      well-known that autobiographic amnesia usually attributed to psychogenic
      etiology, the differential diagnosis of the similar selective retrograde amnesia
      by organic etiology is important.

PMID- 10065462
TI  - [Frontoparietal dementia and parkinsonism: autopsy report of a sporadic case].
AB  - We report a 75-year-old man who presented with parkinsonism, dementia and
      vertical gaze palsy. Postmortem examination revealed frontoparietal atrophy and
      nigral depigmentation. The temporal lobe was well preserved. Histologically, the
      affected cerebral cortex showed vacuolation and neuronal loss in layers 2 and 3.
      The substantia nigra and globus pallidus were also affected. There was gliosis in
      the thalamic medial nuclei and midbrain tegmentum. Neither ballooned neurons nor
      taupositive, argyrophilic inclusions could be found. Moreover, there was no
      Alzheimer pathology manifested by senile plaques and neurofibrillary tangles. In
      fact, the clinical and pathological features of the present case were consistent
      with those observed previously in two other cases reported elsewhere (Kawasaki et
      al. Acta Neuropathol 91: 140, 1996). In these cases, corticobasal degeneration
      (CBD) and frontotemporal dementia (FTD) were considered to be the principal
      entities in the differential diagnosis. However, we believe that these three
      cases, including the present one, were not examples of CBD or FTD, since neither
      ballooned neurons nor tau abnormalities were present, and the precentral gyrus
      was the area most severely involved, the temporal lobes being obviously spared.
      Therefore we considered that they might represent a hitherto unrecognized new
      disease entity.

PMID- 10065463
TI  - [A case of peduncular hallucination after aneurysmal subarachnoid hemorrhage].
AB  - We reported a case of peduncular hallucination after aneurysmal subarachnoid
      hemorrhage (SAH). The patient underwent endovascular embolization of an
      intracranial aneurysm using the Guglielmi detachable coils (GDCs) 9 days after
      SAH. On the 11th day, she reported visual hallucination: a maggot was on the
      ceiling, or a soldier who wore green clothes was standing by a locker. The
      hallucination was vivid, well-formed and associated with insomnia, suggesting
      peduncular hallucination. A computed tomographic (CT) scan revealed small
      infarctions of right frontal lobe, which were not responsible for the visual
      hallucination. Hyperdynamic therapy relieved the visual hallucination 23 days
      after SAH. It was conceivable that vasospasm was the cause of the infarction and
      visual hallucination. Only 4 cases with peduncular hallucination after SAH were
      reported in conjunction with vasospasm. The symptom may be concealed by
      disturbance of consciousness. Visual hallucination should be considered as a sign
      of cerebral vasospasm, and an appropriate treatment should be done at right time.

PMID- 10065464
TI  - [Steroid-responsive diffuse cerebral white matter lesions in a case of
      intractable fungal meningoencephalitis].
AB  - We report a case of fungal meningoencephalitis with steroid-responsive diffuse
      cerebral white matter lesions. A 49-year-old male developed auditory
      hallucination, confusion and fever, on April, 1994. He was diagnosed as having
      cryptococcal meningoencephalitis based on the detection of cryptococcal antigens
      in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole
      resulted in improvement of his neurologic symptoms and CSF findings. For the next
      seven months, he was treated with oral fluconazole and the neurological status
      was stable. However, soon after the dose of fluconazole was tapered, he became
      confused and febrile, which made him admitted to our hospital. Neurological
      examination on admission showed disturbance of consciousness, disorientation and
      meningeal irritation. The CSF examination revealed mild pleocytosis (mostly
      lymphocytes), elevated protein and normal glucose levels, although fungus was not
      detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense
      lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed
      spotty enhanced lesions in the periventricular white matters. The neurologic
      symptoms were once relieved after intravenous administration of fluconazole was
      started, but two months later, he became comatose and needed ventilatory support,
      despite amphotericine B therapy. Then, a needle brain biopsy targeting the white
      matter lesion was done. Histopathology of the specimen showed chronic
      inflammation with granuloma formation and T lymphycyte infiltrate around the
      small vessels, though fungus was not detected in the tissue. Combined therapy
      with corticosteroid and antifungal agents remarkably improved the neurological
      symptoms as well as the MRI findings. In the present case, fungal infection
      possibly induced an altered immune reactions which resulted in the steroid
      responsive diffuse cerebral white matter lesions.

PMID- 10065465
TI  - [FLAIR images MRI in a patient with herpes simplex encephalitis].

PMID- 10065466
TI  - [Spinal arteriovenous malformation with ischemic myelopathy diagnosed on high
      field-strength magnetic resonance imaging].

PMID- 10065467
TI  - [A 96-year-old man with consciousness disturbance, convulsion, and left
      hemiplegia of acute onset].
AB  - We report a 96-year-old Japanese man who developed a sudden onset of left
      hemiplegia and coma. He was found to have diabetes mellitus, hypertension, and
      atrial fibrillation since 1996 with occasional episodes of congestive heart
      failure. He was otherwise apparently well until July 5 of 1997 when he developed
      a sudden onset of unresponsiveness and convulsion involving his right hand and
      was admitted to our hospital. On admission, his BP was 210/120 mmHg, heart rate
      76/min and irregular, BT 36.5 degrees C, and Cheyne-Stokes respiration. General
      medical examination was otherwise unremarkable. Neurologic examination revealed
      semicoma, conjugated deviation to the right, loss of oculocephalic response, left
      facial paresis of central type, flaccid left hemiplegia, and bilateral Babinski
      sign. Pertinent laboratory findings are as follows: BUN 47 mg/dl, creatinine 1.46
      mg/dl, GPT 69 IU/l, LDH 1,142 IU/l, and CK 385 IU/l. A chest x-ray film revealed
      cardiac enlargement and EKG showed left ventricular hypertrophy and atrial
      fibrillation. Cranial CT scan revealed low density areas involving the right
      anterior cerebral and the right posterior cerebral artery territories. He was
      treated with an intravenous osmotic agent and short course of intramuscular
      steroid. He remained unconscious despite these treatment and developed sudden
      cardiopulmonary arrest three weeks after the admission. The patient was discussed
      in a neurological CPC and the chief discussant arrived at the conclusion that the
      patient had suffered from cerebral embolism of cardiac origin. The cause of the
      death was ascribed to acute subendocardial myocardial infarction. Most of the
      participants agreed with this conclusion. Postmortem examination revealed an old
      subendocardial myocardial infarction involving the posterior septal region and
      posterolateral wall of the left ventricle. Neuropathologic examination revealed
      hemorrhagic infarctions involving the territories of the right anterior cerebral,
      right middle cerebral, right posterior cerebral, and left anterior cerebral
      arteries. The left A1 portion of the anterior cerebral artery was hypoplastic,
      and the left pericallosal artery appeared to have been receiving blood supply
      from the right anterior cerebral artery through the anterior communicating
      artery. The large arteries in the base showed marked arteriosclerosis;
      particularly, the initial portion of the right posterior artery showed near
      complete arteriosclerotic occlusions. These characteristic arterial changes
      appeared to be the reason why this patient suffered from an extensive infarction
      from what appeared to have been a single episode of cerebral embolism probably
      initially involving the right internal carotid artery.

PMID- 10065468
TI  - [Anatomy and kinematics of the human ankle joint].
AB  - In the ankle (talocrural) joint, the lower end of the tibia and fibula embrace
      the trochlea tali. Thus, an approximately uniaxial joint is formed which permits
      dorsiflexion and plantarflexion of the foot against the leg. Due to the geometry
      of the trochlea tali, conjunct lateral rotation of the fibula against the tibia
      occurs at the tibiofibular articulations synchronously with active dorsiflexion
      at the ankle joint. Movements at the talocrural joints are mainly limited by the
      opposing muscles as well as by strong collateral ligaments. Talus and calcaneus
      form a functional unit connected by posterior and anterior articulations. The
      posterior articulation is the subtalar (talocalcaneal) joint; in the anterior
      articulation, talar facets of the calcaneus together with the posterior surface
      of the navicular and the superior fibrocartilaginous surface of the plantar
      calcaneonavicular ligament form a concavity for the talar head. Thus, the
      talocalcaneonavicular joint is a compound and--like the subtalar joint--a
      multiaxial articulation. On the weight-bearing foot, the distal tarsus and
      metatarsus are pronated and supinated against the talus in order to maintain
      plantigrade contact. When the foot is off the ground, these movements are
      modified to eversion and inversion, also involving the calcaneocuboid joint. In
      addition, movements between the calcaneus and cuboid also occur during pronative
      or supinative changes between the fore- and hindfoot. Limitation of movements is
      due to leg muscles as well as strong ligaments. Finally, the cuneonavicular,
      cuboideonavicular, intercuneiform and cuneocuboid joints permit some additional
      alterations of the loaded foot in contact with the ground.

PMID- 10065469
TI  - [New therapeutic possibilities for ankle injuries].
AB  - The demand for minimally invasive techniques and more comfort for the patient is
      becoming higher and higher. In the region of the ankle joint, it is therefore
      ideal to use the arthroscope for pathology. Indications for ankle joint
      arthroscopy are: soft tissue impingement, ligament instability, impingement in
      the syndesmosis, osteochondral lesions, loose bodies, arthrosis, and loose os
      trigonum of the talus. In the subtalar joint the indications are rupture of the
      ligaments, loose bodies, and synovitis with soft tissue impingement. A new
      indication is arthroscopically assisted arthlodesis of the talar and subtalar
      joint. The reported high incidence of complications, especially in terms of
      neurovascular lesions, can be avoided by an exact knowledge of anatomy and use of
      non-invasive distraction of the joint.

PMID- 10065470
TI  - [Acute ankle injuries].
AB  - The diagnosis of lateral collateral ankle ligament trauma is based on patient
      history, clinical examination, and clinical stress tests. If the clinical stress
      test is positive, stress radiography could be performed. There is no consensus
      about the usefulness of stress radiography in acute ankle sprain, particularly
      about the cut-off talar tilt angle beyond which a two-ligament rupture would be
      certain, ranging from 5 degrees to 30 degrees. Today MRI is not used for this
      indication, although it allows, with controlled positioning of the foot and with
      defined sections, visualization of injured lateral collateral ankle ligaments. In
      ankle injuries, plain radiographs form the established basis of diagnostic
      imaging and can provide definitive answers in most cases. CT is used in complex
      fractures for complete visualization. MRI is the method of choice for several
      diagnostic problem cases, including occult fractures and post-traumatic avascular
      necrosis. In tendon injuries, MRI is important if ultrasound is not diagnostic.
      Generally, for the evaluation of acute ankle injuries, MRI is the most important
      second-step procedure when radiographs are nondiagnostic.

PMID- 10065471
TI  - [Epiphyseal injuries of the distal tibia. Does MRI provide useful additional
      information?].
AB  - Plain film radiography often underestimates the extent of injury in children with
      epiphyseal fracture. Especially Salter-Harris V fractures (crush fracture of the
      epiphyseal plate) are often primarily not detected. MRI of the ankle was
      performed in 10 children aged 9-17 (mean 14) years with suspected epiphyseal
      injury using 1.0-T Magnetom Expert. The fractures were classified according to
      the Salter-Harris-Rang-Odgen classification and compared with the results of
      plain radiography. In one case MRI could exclude epiphyseal injury; in four cases
      the MRI findings changed the therapeutic management. The visualisation of the
      fracture in three orthogonal planes and the possibility of detection of cartilage
      and ligamentous injury in MR imaging makes this method superior to conventional
      radiography and CT. With respect to radiation exposure MRI instead of CT should
      be used for the diagnosis of epiphyseal injuries in children.

PMID- 10065472
TI  - [Stress X-ray of the ankle joint: a cost-benefit analysis].
AB  - Over an 18-month period findings of stress X-ray of the ankle and medical records
      of 112 cases were analyzed retrospectively as to indications, results and
      therapeutic consequences. The analysis showed that critical setting of
      indications can reduce the frequency of stress X-ray of the ankle and thus lower
      the total costs. The introduction of guidelines could be advantageous at medical
      training institutions.

PMID- 10065473
TI  - [13-MHc high frequency ultrasound of the lateral ligaments of the ankle joint and
      the anterior tibia-fibular ligament. Comparison and results of MRI in 64
      patients].
AB  - PURPOSE: Determination of the value of 13-MHz high-frequency ultrasound in the
      diagnosis of acute injuries of the lateral ankle ligaments and the anterior
      tibiofibular ligament by comparison with MRI. METHOD: Sonography was performed
      prospectively in 64 acutely injured patients using a mechanical 13-MHz sector
      probe; for diagnosis of the anterior tibiofibular ligament a 15-MHz sector probe
      was employed during the course of this trial. Using a 0.2-T unit for MRI
      examination, T1-weighted (TR 580 ms, TE 24 ms) and T2-weighted (TR 3000 ms, TE 80
      ms) spin-echo sequences were obtained in various oblique axial imaging planes.
      RESULTS: In the differentiation of intact and injured ligaments, ultrasound and
      MRI agreed in 95.3% of cases for the anterior fibulotalar ligament, in 88.3% for
      the fibulocalcanear ligament and in 85.0% for the anterior tibiofibular ligament.
      CONCLUSION: Lesions of the anterior talofibular and fibulocalcanear ligament can
      be accurately demonstrated by ultrasound if a 13-MHz sector scanner is used. The
      detection of lesions in the anterior tibiofibular ligament is more difficult.
      With increasing experience and by using a 15-MHz sector scanner, better results
      can be expected for this ligament.

PMID- 10065474
TI  - [MRI of the ankle joint. Comparison of the 1.0-T and the 0.2-T units].
AB  - PURPOSE: Comparison of ankle joint injuries with different MR systems and at
      different field strengths. METHOD: Ten patients with acute ankle injuries were
      examined using mid-field (1.0 T) and dedicated low-field (0.2 T) MR units.
      Findings of ligamentous injury, sinus tarsi involvement, bone injury, and tendon
      injury were correlated. RESULTS: There was no significant difference between mid-
      and low-field MR imaging for ligamentous injuries (chi 2 = 0.0395), sinus tarsi
      changes bone injuries (chi 2 = 0.0507; critical value = 5,991). CONCLUSION: This
      study showed good agreement in pathological findings in ankle injury on mid-field
      and low-field MR imaging.

PMID- 10065475
TI  - [MRI arthrography of the ankle joint].
AB  - Due to its superior soft tissue contrast conventional MRI is the imaging method
      of choice in the evaluation of ankle joint disorders. Conventional MR imaging can
      accurately demonstrate normal or acutely injured ligaments; however, in subacute
      and chronic injury joint fluid necessary for delineation of injured ligaments is
      absent and MR arthrography should be performed. MR arthrography uses the
      intraarticular injection of contrast material to distend the joint, yielding
      improved discrimination of intraarticular structures. This joint distension with
      MR arthrography is also helpful in the staging of osteochondritis dissecans,
      since in cases of unstable lesions tracking of contrast material into the
      interface can be more easily demonstrated. Finally, high contrast and joint
      distension by MR arthrography improves the detection of intraarticular loose
      bodies, which often require surgery. MR arthrography, although invasive, may
      provide additional information in various ankle joint disorders.

PMID- 10065476
TI  - [Chronic diseases of the ankle joint].
AB  - The etiology of chronic diseases of the ankle joint comprises a wide spectrum
      including chronic inflammatory processes and chronic degenerative, tumorous and
      neuropathic processes, as well as some specific syndromes based on chronic
      changes of the ankle joint. Of the inflammatory processes, chronic juvenile
      arthritis (JVC) is the most common disease. However, also Reiter disease,
      psoriasis or chronic monoarthritid diseases such as gout, as well as
      granulomatous diseases (tuberculosis, sarcoidosis) and fungal infections, may
      affect the ankle joint in a chronic course. Chronic degenerative changes are
      usually secondary due to abnormal positioning of the joint constituents or
      repetitive trauma. Neuropathic changes, as frequently seen in the course of
      diabetes, present with massive osseous destruction and malposition of the
      articular constituents. Chronic osseous as well as cartilaginous and synovial
      changes are seen in hemophilic patients. Chronic traumatic changes are
      represented by pigmented villonodular synovitis (PVNS), and chondromatosis, both
      with a predilection for the ankle joint. Due to the possibilities of magnetic
      resonance imaging (MRI), diagnosis of chronic ankle changes includes chronic
      ligamentous, tendinous and soft tissue changes. With the use of MRI, specific
      syndromes can be defined which particularly affect the ankle joint in a chronic
      way, such as the os trigonum syndrome, the anterolateral impingement syndrome and
      the sinus tarsi syndrome. Nevertheless, plain film radiographs are still the
      basic element of any investigation. MRI, however, can be potentially used as a
      second investigation, saving an unnecessary cascade of investigations with
      ultrasound and CT. The latter investigations are used only with very specific
      indications, for instance CT for subtle bone structures and sonography for a
      limited investigation of tendons or evaluation of fluid. Particularly due to the
      possibilities of MRI and the development of special gradient-echo imaging or high
      resolution coils, the investigation of the ankle joint still offers a wide
      spectrum of innovation for the next years, which is particularly enforced by the
      increasing demand for specific diagnosis of chronic diseases in orthopedic
      medicine.

PMID- 10065477
TI  - [Rheumatic diseases of the ankle joint and tarsus].
AB  - Diseases of the hindfoot are associated with considerable functional impairment
      and therefore may hamper patients' movements during gait considerably. Because of
      biomechanical overload, articular structures, tendons and ligaments are prone to
      early degenerative changes during the course of rheumatic diseases as visible
      with plain film radiography, sonography (US), or magnetic resonance imaging
      (MRI). Findings may occur as arthritis of major joints or in the form of
      fibroostitis and bursitis of the os calcis. Despite the progressive course of
      rheumatic diseases and characteristic imaging findings, high variability of X-ray
      signs may occur. Plain film radiograms and high-resolution ultrasonography play a
      key role in imaging rheumatic diseases of the hindfoot. MRI supports imaging
      diagnosis in selected cases. The principal goals of diagnostic imaging are
      precise and reproducible documentation of morphologic abnormalities and
      differentiated analysis for planning proper conservative or surgical treatment.

PMID- 10065478
TI  - [The childhood ankle joint. Deformities, abnormalities and clinical variations].
AB  - The ankle joint unites high functionality with high load on a small surface.
      Congenital as well as acquired variations lead to a derangement of the complex
      concerted action of tendons, ligaments and joints. This causes dysfunction and
      the development of typical deformities. It is necessary to discriminate
      physiological variants, congenital, posttraumatic and tumoral variations for the
      differential diagnosis. In most instances this is only possible with the aid of
      radiological clarification. Congenital malformations in the region of the upper
      and lower ankle joint are generally rare. One disease is club foot, with
      malposition and deformity in the upper and lower ankle joint. Extreme malposition
      can also be found in talus verticalis and congenital hypoplasias and aplasias of
      fibula and tibia. A rather frequently found disease, which first occurs in the
      adolescence, is osteochondrosis dissecans.

PMID- 10065479
TI  - [Diagnostic value of signal-enhanced color Doppler sonography in reactively
      enlarged lymph nodes].
AB  - PURPOSE: This prospective study was performed to investigate characteristic
      sonomorphological features and vascularity of reactively enlarged lymph nodes.
      METHOD: We examined 40 patients with enlarged lymph nodes of the neck by Doppler
      sonography before and after administration of an ultrasound signal-enhancing
      agent. Peak flow velocity, pulsatility- and resistant indices were assessed.
      Lymph nodes were sonomorphologically classified into three groups: homogeneous
      parenchyma (1), a centrally located echogenoic line (2) and an echogenoic "hilus
      reflex" (3). The quantitative and qualitative criteria were compared to
      histological findings. RESULTS: A total of 15 lymph nodes appeared homogeneous. A
      centrally located echogenoic line was found in 17 (42.5%) nodes and echogenoic
      "hilus reflex" in 8 (20%). These sonomorphological patterns correlate to hilus
      fibrosis in the histological specimen. In 32.5% (13) of the nodes the analysis of
      vascularity was possible only after application of the galactose-based ultrasound
      signal enhancer. Quantitative analysis did not result in specific new aspects.
      CONCLUSIONS: Reactive lymph nodes show typical sonomorphological features.
      Administration of an ultrasound enhancer allows assessment of a characteristic
      nodal vascualrity.

PMID- 10065480
TI  - [Painless buccal swelling. Parotid emphysema].

PMID- 10065481
TI  - [Heart diseases in thoracic radiographic images. I].

PMID- 10065483
TI  - [Current status and progress in scientific rehabilitation research].
AB  - When compared to the entire field of health research, to the significance and
      role of rehabilitation in the health care system, to future developments in
      demand and to international developments, the field of rehabilitation in Germany
      has formerly suffered from a considerable deficit in research regarding both
      structure and content. The German Federal Ministry of Research and the German
      Statutory Pension Insurance have now established a common focus in research. This
      decision reflects not only a new political attitude toward the promotion of
      research but also represents the initiation of attempts to overcome existing
      research deficits permanently by means of an extensive programme for the
      promotion of research. In addition to the construction of a scientific
      infrastructure, the funders most importantly expect results that will contribute
      to the further optimisation of effectiveness and efficiency in rehabilitation
      services. An improved scientific foundation of rehabilitative practice will also
      assist the field of rehabilitation in finding greater socio-political recognition
      as an interdisciplinary field. In order to achieve the demanding goals of this
      promotion of research, the promoters will accompany the programme with efficient
      scientific management and quality assurance. The statutory pension insurance
      institutes will systematically analyse the expected research results and offer
      recommendations and suggestions for realisation in dialogue with scientific
      experts and specialist practitioners.

PMID- 10065484
TI  - [The "rehabilitation sciences" promotional emphasis--a promotional program and
      its implementation].
AB  - The German Federal Research Ministry and the German pension insurance have set up
      a special funding programme for medical rehabilitation research. Eight regional
      research networks with about 70 projects receive funds for a first three year
      period. Rehabilitation experts from several countries selected the promising
      networks and studies from more than 100 proposals. In these networks medical and
      social scientists from universities and other research units cooperate with
      rehabilitation centers and pension insurance institutes in order to combine
      forces for the development of German rehabilitation science. The programme aims
      at improving the research structures and at tackling the major challenges of
      medical rehabilitation research. The following subjects represent the main fields
      of the ongoing research: a) etiology, course and prognosis of chronic diseases
      and their consequences to rehabilitation, b) diagnostics in rehabilitation, c)
      evaluation and improvement of rehabilitation therapy, d) the patient's
      perspective in rehabilitation and e) rehabilitation system research. As yet
      funding is limited to the year 2001. Further support of the networks will depend
      on the results of a thorough evaluation of the progress of their research and
      their structural perspective.

PMID- 10065485
TI  - [Freiburg/Bad Sackingen Scientific Rehabilitation Research Group].
AB  - The Freiburg/Bad Sackingen Rehabilitation Research Network aims on problem
      solutions in rehabilitation in Germany. The core concept of the Research Group is
      "goal orientation in diagnosis, therapy and evaluation". This concept refers to
      both individual goals of patients and structural measures. The 13 projects of the
      Research Group deal with topics such as "specific communication problems in
      rehabilitation", "differential indication", "health economics", "methods", and
      "intervention and evaluation". To establish a long-term internal network in the
      Research Group and to facilitate intensive communication and co-operation between
      the various university-based and non-university-based institutions of
      rehabilitation in the Research Group area, Project Management and Methodological
      Support Offices were created.

PMID- 10065486
TI  - [Berlin-Brandenburg-Saxony Rehabilitation Research Group].
AB  - The principal subject of the Rehabilitation Research Network of Berlin,
      Brandenburg and Saxony (BBS) is "the theoretical and practical bases of the
      organisation and economics of rehabilitation". What is involved is a nation-wide
      analysis of the rehabilitation system, i.e. obtaining empirical information on
      the question as to what organisational forms are currently used to carry out
      rehabilitation and what results are achieved. This empirical stocktaking also
      includes economic aspects as far as possible. This study is to serve as a basis
      for developing, testing and implementing steps to rationalise steering mechanisms
      in the rehabilitation system. The first aspect to be studied is "national
      steering problems in institutionalised forms of rehabilitation". The focus is on
      projects on information management and performance and quality management in
      rehabilitation sciences as well as on the actual work of a number of bodies
      paying for rehabilitation (Bundesversicherungsanstalt fur Angestellte,
      Landesversicherungsanstalten) as well as rehabilitation facilities (clinics
      etc.). The two other focuses of the study will examine "rehabilitative adjustment
      to remedies and technical aids/prostheses" and problems facing "family members in
      the context of rehabilitation". In studying these two areas, we are particularly
      interested in examining the interaction between institutionalised aspect of
      rehabilitation and informal factors both inside and outside the system. The BBS
      approach is supported by close co-operation with the regional pension insurance
      institutes (BfA, LVAs) with regard to both the data model and steps being taken.
      The principal instrument of co-operation is the "Gesellschaft fur
      Rehabilitationswissenschaften e.V." (Society for Rehabilitation Sciences). In
      Berlin the BBS co-operates with Free University, the Technical University and the
      Robert Koch Institute and in Saxony with the universities in Dresden and Leipzig.
      Responsibility for scientific questions in the BBS lies with the Institute for
      Rehabilitation Sciences of Berlin's Humboldt University.

PMID- 10065487
TI  - [The North German Group for Rehabilitation Research].

PMID- 10065488
TI  - [Introduction of the Bavarian Scientific Rehabilitation Group].
AB  - As a part of the Rehabilitation Research Programme of both the Ministry for
      Education, Science, Research and Technology and the German Pension Insurance, the
      Rehabilitation Research Network of Bavaria has begun its work after having
      completed a planning phase of three years. Under the heading entitled "Patients
      in Rehabilitation" physical, psychological and social consequences of chronic
      diseases are addressed from a bio-psycho-social point of view. The network
      contains ten research projects which are located in different university
      institutions and rehabilitation clinics all over Bavaria. These projects can be
      assigned to three thematic clusters: diagnostical and predictor studies;
      evaluation of treatments; interface problems in rehabilitation. The interventions
      to be evaluated are aimed at strengthening patients' coping abilities. Wherever
      feasable, randomized controlled studies are performed. Both economical and gender
      specific effects are investigated. A central facility for coordination and
      methodological consultation was implemented at the University of Wurzburg. The
      network has the objective of both improving the quality of rehabilitation
      research and education and increasing the resources of institutions doing
      rehabilitation research in Bavaria.

PMID- 10065489
TI  - [North Rhine-Westphalia Scientific Rehabilitation Group--"future strategies for
      rehabilitation"].
AB  - This Northrine-Westfalian integrated research system in rehabilitation aims at
      the development of future strategies for medical rehabilitation. The well known
      deficits of rehabilitation have led to different complementary projects. These
      comprise research on the lack of evidence in efficacy, predictors for outcomes,
      international cooperation, university related curricula in training,
      implementation of health economics and disease management, and finally the need
      for an actual adaptation of social legislation. The research topics have been
      transformed into key themes which will be coherently integrated by additional
      external expert knowledge acquired in workshops organized by a task force group
      for the development of future strategies.

PMID- 10065490
TI  - [Ulm Scientific Rehabilitation Research Group--"building blocks in
      rehabilitation"].
AB  - The Rehabilitation Research Network of Ulm on "Bausteine der Reha" consists of
      several departments of the University of Ulm, and various rehabilitation
      hospitals and cooperates with a pension insurance institute (LVA Wuerttemberg).
      The aim of this interdisciplinary approach is to evaluate process and outcome of
      rehabilitation measures considering specific clinical and rehabilitative
      questions with main emphasis on epidemiological and economic aspects. The
      Rehabilitation Research Network of Ulm is subdivided into clinical projects and
      cross-sectional subjects. The clinical studies deal with cardiovascular and
      neurological rehabilitation and rehabilitation in disorders of the
      musculoskeletal system. The cross-sectional topics contain special fields such as
      biometry, health economics, epidemiology and occupational rehabilitation. All
      participating institutions have access to a central database with uniform
      structure of the data.

PMID- 10065491
TI  - [Lower Saxony/Bremen Scientific Rehabilitation Research Group].
AB  - The Network for Rehabilitation Research Niedersachsen/Bremen (RFNB) combines the
      competencies of different disciplines and regional agents/institutions in the
      field of rehabilitation, hence creating a network of interdisciplinary
      rehabilitation research to support the further development of research
      methodology, to initiate studies whose results can be fed back to practice and be
      used for education and further qualification. The current research projects of
      the RFNB are focussing on outcome parameters such as prediction, optimization of
      interventions and costs in successful rehabilitation.

PMID- 10065492
TI  - [Saxony-Anhalt/Necklenburg-Vorpommern Scientific Rehabilitation Research Groups].
AB  - Interfaces in Medical rehabilitation are the central target of the research
      collaboration in Sachsen-Anhalt/Mecklenburg-Vorpommern. Six scientific projects
      and one inter-project initiative aim at questions and problems concerning
      regional rehabilitation resources, the motivation of applicants and ways of
      access to rehabilitation, steering mechanisms in the allocation of medical
      rehabilitation, stages and phases in the rehabilitation system, cost
      effectiveness of out-patient rehabilitation and ways and means of adaptation of
      medical rehabilitation to Job requirements. Research focuses on rehabilitation in
      persons with chronic back pain, traumatic and vascular CNS injury and coronary
      infarction.

PMID- 10065493
TI  - [Gastroenterology].

PMID- 10065494
TI  - [Ribavirin/interferon-alpha combination in treatment of chronic hepatitis C: what
      is the status today?].

PMID- 10065495
TI  - [1998 oncologic highlights: difficult choices--no inferior quality].

PMID- 10065496
TI  - [The goal in treating arterial hypertension].

PMID- 10065497
TI  - [Nephrology 1998].

PMID- 10065498
TI  - [Endocrinology 1998].

PMID- 10065499
TI  - [Geriatrics 1998: "hope" for all].

PMID- 10065500
TI  - [Molecular pediatrics: "childhood illnesses" as pioneers in medicine].

PMID- 10065501
TI  - [HIV infection in the child: is there hope on the horizon?].

PMID- 10065502
TI  - [Progress in orthopedics 1998].

PMID- 10065503
TI  - [1998 highlights in surgery: reducing invasiveness, technology, specialization].

PMID- 10065504
TI  - [Individual therapy in gynecology is requested!--does evidence based medicine
      help?].

PMID- 10065505
TI  - [Skin (cancer), hair and sweat].

PMID- 10065506
TI  - [Translocation of the retina in senile macular degeneration].

PMID- 10065507
TI  - [Photosensitization caused by 5-fluorouracil (5-FU)].

PMID- 10065508
TI  - [Migraine and prevention of migraine: the value of magnesium].
AB  - Migraine (with and without aura) is characterised by a marked heterogeneity of
      clinical symptoms. A variety of pathophysiological models has been proposed and a
      multitude of prophylactic strategies recommended. It appears that prophylaxis is
      still problematic, despite considerable progress in acute treatment. Most
      substances used for the former purpose either have substantial side effects or a
      wide range of contraindications. Magnesium (Mg) seems to play a significant role
      in the pathogenesis of migraine. A few clinical trials have produced preliminary
      evidence of therapeutic efficacy. There is a reasonable amount of empirical
      evidence, and further research is warranted considering its low cost and
      favourable side effects profile. An attempt at prophylaxis in mild to mid-severe
      migraine with a daily dose of 600 mg (about 50 mEq) Mg seems to be justified.

PMID- 10065509
TI  - Imaging of the abdominal aorta during examination of patients referred for
      transthoracic echocardiography.
AB  - BACKGROUND: Screening for aneurysm of abdominal aorta (AAA) in the general
      population is costly and unrealistic, but examination of the abdominal aorta
      appears reasonable in a high risk cardiological population. METHOD: As the
      abdominal aorta is easily accessible to standard transthoracic echocardiographic
      equipment, we tested this hypothesis in 301 consecutively referred patients (182
      men, 119 women, mean age 58.6 +/- 16.5 years) by imaging the abdominal aorta at
      the end of the cardiac examination. RESULTS: After exclusion of three patients
      operated on for AAA before, the native infrarenal segment most often involved in
      AAA was visualised in 297 out of 298 patients (99.7%), and the aortic bifurcation
      was seen satisfactorily in 285 of them (95.6%). The abdominal aorta was dilated
      (> or = 2 cm) in 44 patients (15%), all but one of whom were > 50 years old; 17
      of these (5.7%) had AAA defined as segmental dilation with a maximum diameter of
      > or = 3 cm (15 men, 2 women, age 67.4 +/- surgical repair and one endovascular
      repair within one year after completion of the data collection. Their mean age
      was 70.1 +/- 7.9 years, ranging from 58 to 80 years. No significant surgical
      morbidity and no mortality was observed. CONCLUSIONS: Prevalence of dilative
      alterations of the abdominal aorta is high in cardiological patients.
      Visualisation during transthoracic echocardiography of the most important
      infrarenal segment is nearly always feasible (99.7%), including its bifurcation
      (95.6%). Since detection of life-threatening but asymptomatic AAA may save lives
      by offering safe elective surgical treatment or stenting, opportunistic
      examination of the abdominal aorta during routine transthoracic echocardiography,
      which involves little time and no additional cost, would appear to be highly
      effective and should be included in routine examinations, at least in patients
      over 50 years of age.

PMID- 10065510
TI  - [CA19-9 has no value as a tumor marker in obstructive jaundice].
AB  - In the differential diagnosis of pancreatic cancer, CA19-9 appears to be the most
      sensitive and specific marker currently in use. In the absence of jaundice and at
      levels greater than 1000 U/ml, the specificity is almost 100%. Levels higher than
      1000 U/ml are very uncommon for benign diseases. We report a case of obstructive
      jaundice due to an impacted stone in the common bile duct with cholangitis, where
      a CA19-9 level of 61,800 U/ml prompted suspicion of a malignant cause. After
      treatment the CA19-9 returned to a normal level. One year postoperatively neither
      abdominal ultrasound nor CT-scan showed any sign of intraabdominal malignancy.
      Reviewing the literature, we conclude that even very high levels of CA19-9 in
      cases with obstructive jaundice can be caused by benign diseases. Unlike other
      tumour markers (alpha-foetoprotein, carcinoembryonic antigen), where exceedingly
      high levels are definitely caused by malignancy, high levels of CA19-9 can be
      caused by benign obstructive jaundice. In such cases CA19-9 is useless as a
      tumour marker. The biliary obstruction must be treated successfully and more
      diagnostic procedures or even laparotomy performed, to exclude malignancy or
      treat a benign disease.

PMID- 10065511
TI  - [Clinical epidemiology and treatment of tuberculosis in elderly patients].
AB  - In developed countries the incidence of tuberculosis is higher in patients aged
      65 and over than in any other age group, with the exception of HIV positive
      subjects. This high incidence is a consequence of the very high rate of infection
      in our countries in the first part of the century, and of the diminished
      efficiency of the aging immune system. In this age group, most cases of
      tuberculosis are reactivations of dormant mycobacteria. However, the possibility
      of a newly acquired infection must be kept in mind, especially in
      institutionalized patients. The clinical presentation is often insidious and non
      specific, as is the radiological presentation (i.e. infiltrates in middle or
      lower lobes); the large number of cases discovered at autopsy illustrates the
      difficulty of clinical diagnosis. Extra-thoracic involvement is less frequent
      than in younger adults (15% of cases). Mortality is high, even in treated
      patients, and increases with age. The frequency of drug-induced hepatitis under
      tuberculostatic treatment increases with age: signs of hepatic toxicity should be
      monitored regularly; furthermore, compliance with treatment may be jeopardized by
      cognitive impairment: directly observed treatment should be set up when there is
      the slightest doubt as to compliance. Prophylactic treatment with isoniazid is
      indicated in recent tuberculin converters (after exclusion of active disease), in
      patients with diabetes or on immunosuppressive therapy, and in patients with
      radiological fibrotic lesions without serious co-morbidities. In
      institutionalized subjects regular tuberculin testing is warranted to detect
      nosocomial infection.

PMID- 10065512
TI  - [Increasing abdominal girth, muscle weakness and ecchymoses. Adrenal cortex
      carcinoma with liver metastases].

PMID- 10065513
TI  - Cyclic mechanical stretch stress increases the growth rate and collagen synthesis
      of nucleus pulposus cells in vitro.
AB  - STUDY DESIGN: A rabbit model designed to investigate the effects of applied
      cyclic tensile stress on the cell division rate and the collagen synthesis in the
      rabbit nucleus pulposus cells in vitro. OBJECTIVE: To evaluate the effects of
      mechanical stress on nucleus pulposus cells, thus adding to the understanding of
      the adaptation of the intervertebral disc to mechanical stress. SUMMARY OF
      BACKGROUND DATA: Intervertebral disc cells in vivo are exposed to a multitude of
      physical forces during physical motion. Although it is known that in
      intervertebral disc disease, a common pathway of disc degeneration is mechanical
      stress on the nucleus pulposus or the anulus fibrosus or both, the underlying
      mechanism has been less well defined. METHODS: Nucleus pulposus cells were
      isolated from 4-week-old Japanese white rabbits. These cells were subjected to
      the mechanical cyclic stretch stress using a computerized, pressure-operated
      instrument that physically deformed the cells. The DNA synthesis rate, collagen
      synthesis rate, and cell cycle progression were measured. RESULTS: Cyclic tensile
      stretch increased the DNA synthesis rate in nucleus pulposus cells and in the
      population of cells in the S phase of the cell cycle during 1 to 2 days of
      subjugation to stress. Cyclic tensile stretch also increased collagenous protein
      synthesis in nucleus pulposus cells during 1 to 4 days of stress. CONCLUSIONS:
      Mechanical stress on nucleus pulposus cells promotes the proliferation of cells
      and alters the properties of intervertebral disc cells. This study may reflect
      the adaptation of the intervertebral disc to increased motion and stress.

PMID- 10065514
TI  - The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or
      osteoinductive bone protein extract for posterolateral lumbar spine fusion.
AB  - STUDY DESIGN: A posterolateral lumbar arthrodesis animal model using coralline
      hydroxyapatite as a bone graft substitute. OBJECTIVE: To determine the
      effectiveness of coralline hydroxyapatite as a bone graft substitute for lumbar
      spine fusion when used with bone marrow, autogenous bone graft, or an
      osteoinductive bone protein extract. SUMMARY OF BACKGROUND DATA: Coralline
      hydroxyapatite is commonly used as a bone graft substitute in metaphysial defects
      but its use in a more challenging healing environment such as the posterolateral
      spine remains controversial. There are no published animal studies in which the
      use of coralline hydroxyapatite has been evaluated in a posterolateral lumbar
      arthrodesis model. METHODS: Single-level posterolateral lumbar arthrodesis was
      performed at L5-L6 in 48 adult New Zealand White rabbits. Rabbits were assigned
      to one of three groups based on the graft material they received: 3.0 mL
      coralline hydroxyapatite 1.5 mL plus bone marrow; 1.5 mL coralline hydroxyapatite
      plus 1.5 mL autogenous iliac crest bone; and, 3.0 mL coralline hydroxyapatite
      plus 500 micrograms bovine-derived osteoinductive bone protein extract on each
      side. Rabbits were killed after 2, 5, or 10 weeks, and the spines were excised
      and evaluated by manual palpation, radiographs, tensile biomechanical testing,
      and nondecalcified histology. RESULTS: Fusions were assessed by manual palpation
      at 5 weeks for comparisons among the three groups of graft materials. The
      coralline hydroxyapatite used with bone marrow produced no solid fusions (0/14).
      When combined with an equal amount of autogenous iliac crest bone, coralline
      hydroxyapatite resulted in solid fusion in 50% (7/14) of the rabbits (P < 0.05).
      When combined with the osteoinductive growth factor extract, the coralline
      hydroxyapatite resulted in solid fusion in 100% (11/11) of the rabbits (P <
      0.05). The fusion masses in the growth factor group were significantly stronger
      (1.8 +/- 0.2 vs. 1.3 +/- 0.1; P = 0.02) and stiffer (1.5 +/- 0.2 vs. 1.2 +/- 0.1,
      P = 0.04) based on tensile testing to failure when normalized to the adjacent
      unfused level. CONCLUSION: These data indicate that coralline hydroxyapatite with
      bone marrow was not an acceptable bone graft substitute for posterolateral spine
      fusion. When combined with autogenous iliac crest bone graft-coralline
      hydroxyapatite served as a graft extender yielding results comparable to those
      obtained with autograft alone. Coralline hydroxyapatite served as an excellent
      carrier for the bovine osteoinductive bone protein extract yielding superior
      results to those obtained with autograft or bone marrow.

PMID- 10065515
TI  - Biomechanical comparison of spondylolysis fixation techniques.
AB  - STUDY DESIGN: A load-controlled biomechanical analysis of flexion, extension, and
      torsional stiffness in instrumented calf spines. OBJECTIVES: To compare
      biomechanically the performance of various fixation techniques for the repair of
      spondylolytic defects in the pars interarticularis. SUMMARY OF BACKGROUND DATA:
      Several techniques have been developed to stabilize a spondylolytic defect in the
      lumbar spine. There are, however, no comprehensive biomechanical studies in which
      these techniques are compared. METHODS: Nine fresh-frozen and thawed calf
      cadaveric lumbar L2-L6 spines were used for mechanical testing. Scott's
      technique, Buck's technique (screw fixation in the lamina across the defects),
      modified Scott's technique (wire loops around cortical screws placed into both
      pedicles and tightened under the spinous process), and screw-rod-hook fixation
      were applied on the calf lumbar spines in which bilateral spondylolytic defects
      were created in the L4 vertebra. Motion across the defects for each direction of
      loading in flexion, extension, and rotation was measured using extensometers. The
      intervertebral rotations and the strain at the site of the spondylolytic defect
      were computed from the acquired load-displacement data. RESULTS: Each fixation
      technique significantly increased stiffness and returned the intervertebral
      rotational stiffness to nearly intact levels. Displacement across the defect
      under flexion loading was significantly suppressed by each instrumentation
      technique, but the least motion (P < 0.05) was allowed with the screw-rod-hook
      fixation or Buck's technique. CONCLUSIONS: All four fixation techniques restored
      the intervertebral rotational displacements under flexion and torsional loading
      to the intact condition. The screw-rod-hook fixation allowed the least amount of
      motion across the defect during flexion.

PMID- 10065516
TI  - The effect of locking fixation screws on the stability of anterior cervical
      plating.
AB  - STUDY DESIGN: Current anterior cervical plate systems were tested with locked and
      unlocked fixation screws and with unicortical and bicortical fixation screws to
      determine fixation rigidity and pull-off strengths. OBJECTIVES: To evaluate the
      effects of screw-plate locking and screw length on fixation strength and
      stability of anterior cervical plates. SUMMARY OF BACKGROUND DATA: New plate
      systems provide for rigid locking of the screw-plate interface, theoretically
      increasing construct rigidity, allowing unicortical fixation, and preventing
      screw back-out. There are few data on the effects of locking screws on the
      stability of anterior cervical plating. METHODS: Eighty fresh lamb vertebrae (C3
      T1) were used. Test systems included: Cervical Spine Locking Plate (CSLP;
      Synthes, Paoli, PA, Orion plate (Sofamor-Danek, Memphis, TN), and Acroplate
      (AcroMed, Cleveland, OH). The CSLP and Orion plates were tested with fixation
      screws, locked and unlocked, and the AcroMed plate with unicortical and
      bicortical screw purchase. Biomechanical testing of the screw-plate constructs
      was performed to determine the initial bone-plate rigidity and pull-off strength.
      A 2.5-Nm cyclic bending moment was then applied to additional constructs for
      10(5) cycles, and these constructs retested. RESULTS: Locked CSLP and Orion
      constructs were more rigid than all unlocked unicortical systems initially and
      after cyclic loading (P < 0.05). After cycling, the rigidity of all unlocked
      unicortical constructs decreased significantly (P < 0.05). There was no
      significant difference in pull-off strengths between the CSLP, the Orion, and the
      unicortical AcroMed plate. However, all had significantly less pull-off strength
      than the AcroMed plate with bicortical screws. A negative correlation was
      observed between initial pull-off strength and sagittal vertebral body diameter.
      CONCLUSIONS: Locking screws significantly increased the rigidity of the tested
      screw-plate systems initially and after cyclic loading. Because pull-off strength
      was affected by the vertebral body diameter, use of longer unicortical screws may
      be clinically beneficial in the patient with larger cervical vertebrae.

PMID- 10065517
TI  - Facet coverage in children on flexion lateral cervical radiographs.
AB  - STUDY DESIGN: This radiographic study was designed to attempt to develop
      standards of facet coverage (overlap) on lateral cervical radiographs during
      voluntary flexion. OBJECTIVE: To produce normative standards for minimum facet
      coverage in children. SUMMARY OF BACKGROUND DATA: Previous studies on normative
      standards of facet coverage have been performed only in adults. METHODS: Thirty
      six children with minor trauma had lateral flexion-extension radiographs. A
      standard filming sequence was used in all. Facet joint overlap at each level was
      divided by the anteroposterior diameter of the upper adjacent cervical body at
      each level. RESULTS: On linear regression analysis, these ratios did not vary
      significantly with age at C2-C3 through C6-C7. Means and standard deviations were
      determined for C2-C7. CONCLUSIONS: These ratios may prove useful in evaluation of
      children with possible ligamentous injury.

PMID- 10065518
TI  - Do human lumbar discs reconstitute after chemonucleolysis? A 7-year follow-up
      study.
AB  - STUDY DESIGN: A retrospective, longitudinal study of 51 patients, covering a mean
      follow-up period of 81 months. OBJECTIVE: To observe the long-term temporal
      course of the height of human lumbar discs after chemonucleolysis. To document
      whether human lumbar discs reconstitute, thus characterizing the healing
      potential of central disc tissue. SUMMARY OF BACKGROUND DATA: Although
      reconstitution of disc height within some months of chemonucleolysis has been
      observed in animal experiments, human lumbar discs have shown no tendency to
      regain their initial height within 1 year of treatment. To date, there has been
      no report on longer follow-up periods. The different reactions of animal and
      human discs may be dose-related or related to differences in tissue properties,
      physiologic environment or in vivo loading conditions. METHODS: Using a new
      protocol, the heights of lumbar discs were measured from sets of lateral
      radiographic views of 51 patients subject to chemonucleolysis by treatment with
      chymopapain (doses of 4000 or 3000 picokatals [pkat]). The sets comprised a view
      taken before treatment, a view taken (on average) 4 months after treatment, and a
      view taken (on average) 81 months after treatment. In the majority of patients,
      untreated discs adjacent to discs treated with chemonucleolysis served as control
      discs. RESULTS: Shortly after injection of chymopapain, all treated discs
      decreased in height. The height decrease of treated discs amounted to 15.8% on
      average. In the subcohort treated with 4000 pkat, the loss did not reverse during
      the entire follow-up period; in the subcohort treated with 3000 pkat a small
      fraction of the lost height was regained. Untreated neighboring control discs
      showed a minor (3.4%) decrease in height. CONCLUSIONS: Human lumbar discs do not
      reconstitute after chemonucleolysis. Because the long-term temporal course of
      disc height in patients is in disagreement with observations from animal
      experiments, caution is suggested when generalizing results from animal studies
      to humans.

PMID- 10065519
TI  - Variability of strap tension in brace treatment for adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: A mechanical evaluation of brace strap tensions to document their
      variability in different patient positions and to assess their biomechanical
      effectiveness. OBJECTIVES: To measure the strap tensions at which adolescents
      with scoliosis are wearing their braces and to determine the variations in strap
      tension in different patient positions. SUMMARY OF BACKGROUND DATA: The
      biomechanical action of thoracolumbosacral orthoses in still not well understood,
      and there is no standardized strap tension at which the brace should be fastened
      to obtain optimal results. METHODS: This study was conducted in 34 adolescents
      with idiopathic scoliosis wearing thoracolumbosacral orthoses. Brace straps were
      instrumented with load cells and tightened at four tensions (the ones prescribed
      by their treating physician and three standardized values: 20, 40, and 60 N). In
      each case, the tension was recorded while the patients assumed nine positions
      corresponding to normal daily tasks. The variability of strap tension was
      evaluated by comparing the changes from the original standing position. RESULTS:
      The prescribed tensions measured in thoracic and pelvic straps were markedly
      variable. The greatest changes in tension occurred when the patients were lying
      down. Relaxation of strap tension was found when the patients returned to the
      standing position after having completed the tasks. CONCLUSIONS: If strap tension
      affects the biomechanical actions of the brace, these results indicate that
      regular brace strap tension adjustments are needed and raise questions about the
      efficacy of nighttime bracing to correct spinal deformities.

PMID- 10065520
TI  - Complications in the adult spinal deformity patient having combined surgery. Does
      revision increase the risk?
AB  - STUDY DESIGN: A comparison of short-term complications (within 6 months after
      surgery) between primary combined adult spinal deformity (multilevel scoliosis,
      kyphosis, fixed coronal-sagittal imbalance) surgeries (n = 18) and combined adult
      spinal deformity revision surgeries (n = 26). OBJECTIVES: To analyze the short
      term complications and to determine whether revision status increases the risks
      of short-term complications in this group of patients. SUMMARY OF BACKGROUND
      DATA: There is no peer-reviewed article comparing complications of revision to
      those in primary patients in a group of patients undergoing combined surgery for
      adult spinal deformity. METHODS: Major and minor complications were analyzed for
      both patient groups, and demographic data were collected. The demographic data of
      the two groups were very similar. RESULTS: The major (11.1% vs. 7.8%) and minor
      (11.1% vs. 11.5%) complications for the two groups (primary vs. revision) were
      very similar. All patients had combined procedures and all were patients with
      adult spinal deformity. The wound complications were less in those receiving
      total parenteral nutrition (2 of 31) than in those without (2 of 13). The group
      receiving parenteral nutrition was thought to be at higher risk for wound
      complications. CONCLUSIONS: The risk of major and minor complications within the
      first 6 months after surgery is not necessarily greater in the revision group
      than in the primary group of patients with adult spinal deformity who have
      combined surgeries. Total parenteral nutrition does appear to have a role in many
      of these patients.

PMID- 10065521
TI  - The ability of pressure-controlled discography to predict surgical and
      nonsurgical outcomes.
AB  - STUDY DESIGN: A multicenter, retrospective study of long-term surgical and
      nonsurgical patient outcomes, after lumbar discography. OBJECTIVES: To
      investigate the efficacy and surgical outcome predictive value of categorizing
      positive discography findings, using a pressure x pain provocation categorization
      system. BACKGROUND: With the use of pressure-controlled manometric discography,
      improved and more specific diagnostic categorization is possible. The literature
      suggests that more specific categorization of positive discographic findings may
      predict surgical and nonsurgical outcomes. Studies have shown that
      intertransverse fusions may not fully protect the disc from anterior loading.
      Consequently, in patients who have low-pressure-sensitive discs, surgery that
      includes interbody fusion should provide a more favorable long-term outcome than
      intertransverse fusion only. METHODS: Long-term outcome was ascertained in 96
      patients who had lumbar discography and subsequently underwent interbody fusion
      alone, combined fusion, intertransverse fusion or no surgery. Patients were
      retrospectively placed into specific diagnostic categories, according to a four
      point scale. Progressively restrictive subgroups, beginning with the entire
      sample and ending with the most sensitive group (chemically sensitive), were
      examined for long-term surgical outcome differentiation. RESULTS: There were no
      significant differences in long-term surgical outcome across the entire sample.
      However, significant outcome differences existed across the subgroup of patients
      with chemically sensitive discs. In this group, patients undergoing
      interbody/combined fusion had a significantly better outcome than patients who
      had intertransverse fusion. Nonsurgical patients had the worst outcome overall.
      CONCLUSIONS: Patients with highly (chemically) sensitive discs appear to achieve
      significantly better long-term outcomes with interbody/combined fusion than with
      intertransverse fusion. Patients without disc surgery have the least favorable
      outcome. Precise prospective categorization of positive discographic diagnoses
      may predict outcomes from treatment, surgical or otherwise, thereby greatly
      facilitating therapeutic decision-making.

PMID- 10065522
TI  - Higher levels of antibodies against the psoriasis-associated antigen pso p27 in
      cerebrospinal fluid from patients with low back pain and sciatica.
AB  - STUDY DESIGN: A prospective study comparing the presence of antibodies against
      the psoriasis-associated antigen pso p27 in pain-free control subjects and
      patients with low back pain and/or sciatica. OBJECTIVES: To analyze the amount of
      local inflammation present in human lumbar disc disorders, using anti-pso p27
      antibodies in the cerebrospinal fluid as a marker and to analyze whether pain
      intensity correlates with this marker of inflammation. SUMMARY OF BACKGROUND
      DATA: Pso p27 is a major antigen in psoriasis that is also present, mostly
      locally, in other inflammatory disorders, such as sarcoidosis, inflammatory bowel
      disease, and ankylosing spondylitis, inflammation is also thought to play a major
      role in the generation of lumbar and radicular pain in degenerative disc
      disorders. METHODS: Anti-pso p27 antibodies in cerebrospinal fluid were
      quantified using an indirect enzyme-linked immunosorbent assay with pso p27
      obtained from patients with psoriasis for use as an antigen. Fifteen patients
      with spinal stenosis, 11 patients without myelographic disc herniation, 17
      patients with disc herniation, and 24 pain-free patient control subjects were
      studied. RESULTS: Significantly higher levels of anti-pso p27 antibodies were
      found in patients with myelographic signs of disc herniation than in with
      patients with no signs of herniation, patients with spinal stenosis, and control
      subjects. Patients with no known signs of disc herniation and patients with
      myelographic signs of spinal stenosis (< 10 mm in diameter) caused by
      degenerative changes, had higher levels of anti-pso p27 antibodies than did
      control subjects. However, these differences reached only borderline statistical
      significance. CONCLUSIONS: The results support those in previous reports, that
      inflammation probably plays an important role in degenerative disk disorders,
      particularly in disk herniations. That there was no correlation between pain
      intensity and anti-pso p27 activity indicates that the antigen is probably not
      essential in pain generation per se. The results may indicate that pso p27 is
      expressed secondary to, not as an initiator of, inflammation.

PMID- 10065523
TI  - INTERMED--an assessment and classification system for case complexity. Results in
      patients with low back pain.
AB  - STUDY DESIGN: Cross-sectional investigation and follow-up of patients with low
      back pain. OBJECTIVES: To evaluate the capacity of the INTERMED--a
      biopsychosocial assessment and classification system for case complexity--to
      identify patients with a chronic, disabling course of low back pain and to
      predict treatment outcome. SUMMARY OF BACKGROUND DATA: An impressive number of
      biologic and nonbiologic factors influencing the course of low back pain have
      been identified. However, the lack of a concise, comprehensive, reliable and
      validated classification system of this heterogeneous patient population hampers
      preventive and therapeutic progress. METHODS: The INTERMED was used to assess
      patients with low back pain, who participated in a functional rehabilitation
      program (n = 50) and patients with low back pain who applied for disability
      compensation (n = 50). Patients of the rehabilitation program were observed to
      assess the effects of treatments. RESULTS: The INTERMED distinguished between
      patients in different phases of disability and provided meaningful information
      about the biopsychosocial aspects of low back pain. In hierarchical cluster
      analysis two distinct clusters emerged that differed in the degree of case
      complexity and treatment outcomes. CONCLUSIONS: This first application of the
      INTERMED indicates its potential utility as a classification system for patients
      with low back pain.

PMID- 10065524
TI  - Evaluation of the revised NIOSH lifting equation. A cross-sectional epidemiologic
      study.
AB  - STUDY DESIGN: A cross-sectional study of the 1-year prevalence of low back pain
      was conducted in workers employed in manual lifting jobs. OBJECTIVES: To provide
      epidemiologic data to determine the correlation between the prevalence of low
      back pain and exposure to manual lifting stressors, measured with the lifting
      index component of the revised lifting equation from the National Institute for
      Occupational Safety and Health (NIOSH). SUMMARY OF BACKGROUND DATA: The NIOSH
      lifting equation has been proposed as a practical, yet valid tool for assessing
      the risks of low back pain caused by manual lifting. To date, however, there have
      been few studies in which the effectiveness of the equation to identify jobs with
      elevated rates of low back pain has been evaluated. METHODS: Fifty jobs from four
      industrial sites were evaluated with the NIOSH lifting equation. A symptom and
      occupational history questionnaire was administered to 204 people employed in
      lifting jobs and 80 people employed in nonlifting jobs. Regression analysis was
      used to determine whether there was a correlation between the lifting index and
      reported low back pain. RESULTS: As the lifting index increased from 1.0 to 3.0,
      the odds of low back pain increased, with a peak and statistically significant
      odds ratio occurring in the 2 < lifting index < or = 3 category (odds ratio =
      2.45). For jobs with a lifting index higher than 3.0, however, the odds ratio was
      lower (odds ratio = 1.45). CONCLUSIONS: Although low back pain is a common
      disorder, the lifting index appears be a useful indicator for determining the
      risk of low back pain caused by manual lifting.

PMID- 10065525
TI  - Effectiveness of Waddell's nonorganic signs in predicting a delayed return to
      regular work in patients experiencing acute occupational low back pain.
AB  - STUDY DESIGN: Consecutive case series. OBJECTIVE: To determine whether the
      presence of Waddell's nonorganic signs in occupational, acute low back pain
      patients predicts a longer time before return to unrestricted regular work.
      SUMMARY OF BACKGROUND DATA: Waddell's nonorganic signs identify patients with
      chronic low back pain with a poor prognosis; however, they have not been used as
      an outcome predictor in patients with occupational, acute low back pain. METHODS:
      Standardized histories and physical examinations, including Waddell's signs were
      recorded at the first clinic visit (n = 143) by a single physician who was not
      blinded to the study's goals or methods. Those with chronic low back pain or
      complicating medical conditions (n = 88) were excluded. Data from patients
      exhibiting the nonorganic signs were compared with those from patients without
      the signs for time to return to regular work without restrictions and medical
      resource use. RESULTS: Fifty-five patients with acute work-related low back pain
      were included. One or more of the nonorganic signs were seen in 14 patients
      (25.5%) at the first appointment. The most common signs were simulated axial
      loading (78.6%) and simulated rotation (71.4%). Those with any nonorganic sign
      required a median 58.5 days to return to regular work compared with 15.0 days for
      those without (P < 0.0001). Patients exhibiting any nonorganic sign compared with
      those without used more physical therapy (50.0% vs. 12.2%; P < 0.01) and lumbar
      computed axial tomography (21.4% vs. 0.0%; P = 0.01). CONCLUSIONS: Patients with
      acute, occupational low back pain exhibiting Waddell's nonorganic signs had a
      four times lengthier time for return to unrestricted, regular work and a greater
      use of physical therapy and lumbar computed tomographic scans.

PMID- 10065526
TI  - Laparoscopic fusion of the lumbar spine: minimally invasive spine surgery. A
      prospective multicenter study evaluating open and laparoscopic lumbar fusion.
AB  - STUDY DESIGN: Two hundred-forty consecutive patients underwent laparoscopic
      instrumented interbody fusion using custom-designed instrumentation and BAK
      (Sulzer Spine Tech, Minneapolis, MN) fusion cages. The surgeries were performed
      at eight spine centers during U.S. Food and Drug Administration investigational
      device evaluation clinical trials. This cohort was compared with 591 consecutive
      patients undergoing open anterior fusion with the same device. OBJECTIVES: To
      investigate the feasibility and safety of the laparoscopic approach compared with
      that of open procedures. SUMMARY OF BACKGROUND DATA: In other areas of medicine,
      advances in laparoscopic surgical procedures have resulted in reduced morbidity,
      expense, and pain when compared with results of the open counterpart. METHODS:
      The open anterior procedure was performed using a retroperitoneal approach. The
      laparoscopic procedure was performed transperitoneally with carbon dioxide
      insufflation to provide visualization using a 10-mm endoscope. Two hollow,
      titanium, threaded interbody implants packed with autologous bone were inserted
      into the diseased interspace. RESULTS: The laparoscopy group had a shorter
      hospital stay and reduced blood loss but had increased operative time. Operative
      time improved in the laparoscopy group as surgeons' experience increased.
      Operative complications were comparable in both groups, with an occurrence of
      4.2% in the open approach and 4.9% in the laparoscopic approach. Overall, the
      device-related reoperation rate was higher in the laparoscopy group (4.7% vs.
      2.3%), primarily as a result of intraoperative disc herniation. Conversion to
      open procedure in the laparoscopy group was 10%, with most cases predictable and
      preventable. CONCLUSIONS: The laparoscopic procedure is associated with a
      learning curve, but once mastered, it is effective and safe when compared with
      open techniques of fusion.

PMID- 10065527
TI  - Nonsurgical treatment of three-column thoracolumbar junction burst fractures
      without neurologic deficit.
AB  - STUDY DESIGN: Retrospective review of the outcome of neurologically intact
      patients with three column thoracolumbar junction burst fractures that were
      treated nonsurgically. OBJECTIVE: To further define the parameters for
      nonsurgical management of thoracolumbar junction burst fractures. SUMMARY OF
      BACKGROUND DATA: Many texts list involvement of the posterior column as an
      indication for surgery and state that casting or bracing is mandatory. This has
      not been the authors' experience. METHODS: Thirty-eight patients with
      nonpathologic, single-level burst fractures of T11, T12, L1, or L2, and with
      posterior element fractures were studied retrospectively. The selection criteria
      required that the patient be neurologically intact, that the pedicles and facet
      joints not be fractured or dislocated, and that the angle of kyphosis be less
      than 35 degrees. The extent of retropulsion, loss of vertebral height, and
      presence of lamina or process fractures were not criteria. No attempt was made to
      reduce the fracture. Patients were allowed immediate ambulation as tolerated.
      Jewett braces were used in nine patients, but no bracing was used in the
      remainder. RESULTS: There were 22 males, 16 females. Median age 37 years (range,
      16-65). Fracture involved both endplates in 16 patients (12 crush-cleavage type),
      the superior end-plate in 21, and the inferior endplate in 1. The hospital stay
      was from 2 to 18 days (median, 8 days). Follow-up averaged 4.1 years (range, 2.1
      6.3). All patients remained neurologically intact. Eight patients had no pain, 24
      had minimal pain, 4 had moderate pain, and 2 had moderate to severe pain. Twenty
      nine of 38 patients (76%) were able to work at the same level. The initial
      kyphosis angle averaged 20 degrees (range 10-35 degrees). At follow-up it
      averaged 24 degrees (range 12-38 degrees). The maximum increase was 6 degrees.
      Some degree of retropulsed fragment resorption was noted in 35 cases.
      Complications were limited to transient urinary retention. There were no
      thromboembolisms, decubitus ulcers, or pulmonary complications. CONCLUSION:
      Despite the use of less restrictive criteria, no brace, and early activity as
      tolerated, the results are similar to those obtained with more restrictive
      protocols. The presence of vertical lamina fracture, spinous process fracture,
      and transverse process fracture are not contra--indications. Activity restriction
      and bracing may be important for pain control but probably does not change the
      long-term result.

PMID- 10065528
TI  - Thoracic disc herniation mimicking acute lumbar disc disease.
AB  - STUDY DESIGN: Case report of a 49-year-old woman with a lower thoracic disc
      herniation mimicking acute lumbosacral radiculopathy. OBJECTIVE: To describe an
      unusual case of thoracic disc herniation mimicking acute lumbar disc disease.
      SUMMARY OF BACKGROUND DATA: Symptomatic thoracic disc herniation is rare and its
      clinical manifestations differ widely from those of cervical and lumbar disc
      herniations. Midline back pain and signs of spinal cord compression progressing
      over months or years are the predominant clinical features. Acute and subacute
      thoracic disc herniation occurs in less than 10% of patients, and isolated root
      pain is unusual. METHODS: A 49-year-old woman had acute low back pain radiation
      into the left buttock and the lateral aspect of the left leg and left foot.
      Magnetic resonance imaging study showed a bulging disc and posterior osteophytes
      at T11-T12. RESULTS: Surgical removal of the herniated disc and osteophytes
      rapidly relieved her symptoms and neurologic deficits. A follow-up neurologic
      examination 3 years later showed normal motor and sensory functions, although low
      back soreness was noted occasionally. CONCLUSION: A case of thoracic disc
      herniation mimicking an acute lumbosacral radiculopathy is presented. Compression
      of the lumbosacral spinal nerve roots at the lower thoracic level after exit from
      the lumbar enlargement may be the mechanism for this unusual presentation.

PMID- 10065529
TI  - Acidification of the phagosome in Crassostrea virginica hemocytes following
      engulfment of zymosan.
AB  - Phagocytic hemocytes are responsible for engulfing and internally degrading
      foreign organisms within the hemolymph and tissue of the eastern oyster,
      Crassostrea virginica. Since rapid acidification of the phagosome lumen is
      typically essential for activation of hydrolytic and reactive oxygen intermediate
      (ROI) producing enzymes in vertebrate cells, we measured phagosomal pH in oyster
      hemocytes by using the emission fluorescence of two fluorescent probes, rhodamine
      and Oregon Green 488 (OG 488), conjugated to zymosan to determine whether oyster
      hemocyte phagosomes become acidified after phagocytosis of zymosan. The average
      pH of 1079 phagosomes within 277 hemocytes 1 h after phagocytosis of zymosan was
      3.9 +/- 0.03. Observations of 141 hemocytes with internalized zymosan by light
      microscopy revealed that, over a 60-min time period, 51% of highly granular
      hemocytes became partially granular, and 29% became agranular. In addition, 83%
      of partially granular hemocytes containing zymosan at time = 0 became agranular
      within 60 min. A comparison revealed that the phagosomes of agranular hemocytes
      were much more acidic (pH 3.1 +/- 0.02) than those of highly granular hemocytes
      (4.9 +/- 0.02; P < 0.05). These values are significantly lower than most reported
      in the literature for blood cells from metazoan organisms.

PMID- 10065530
TI  - Molecular determination of species boundaries in corals: genetic analysis of the
      Montastraea annularis complex using amplified fragment length polymorphisms and a
      microsatellite marker.
AB  - Analyses of DNA have not been widely used to distinguish coral sibling species.
      The three members of the Montastraea annularis complex represent an important
      test case: they are widely studied and dominate Caribbean reefs, yet their
      taxonomic status remains unclear. Analysis of amplified fragment length
      polymorphisms (AFLPs) and a microsatellite locus, using DNA from sperm, showed
      that Montastraea faveolata is genetically distinct. One AFLP primer yielded a
      diagnostic product (880 bp in M. faveolata 920 bp in M. franksi and M. annularis)
      whose homology was established by DNA sequencing. A second primer revealed a 630
      bp band that was fixed in M. faveolata, and rare in M. franksi and M. annularis;
      in this case homologies were confirmed by Southern hybridizations. A
      tetranucleotide microsatellite locus with several alleles exhibited strong
      frequency differences between M. faveolata and the other two taxa. We did not
      detect comparable differences between M. annularis and M. franksi with either
      AFLPs (12 primers screened) or the microsatellite locus. Comparisons of AFLP
      patterns obtained from DNA from sperm, somatic tissues, and zooxanthellae suggest
      that the technique routinely amplifies coral (animal) DNA. Thus analyses based on
      somatic tissues may be feasible, particularly after diagnostic differences have
      been established using sperm DNA.

PMID- 10065531
TI  - NMR spectroscopic studies of the hydrogenosomal [2Fe-2S] ferredoxin from
      Trichomonas vaginalis: hyperfine-shifted 1H resonances.
AB  - The hyperfine-shifted 1H NMR resonances of oxidized and reduced Trichomonas
      vaginalis ferredoxin, a functionally unique [2Fe-2S] ferredoxin, have been
      studied. The oxidized protein spectrum displayed a pattern of six broad upfield
      shifted resonances between 13 and 40 ppm with chemical shifts distinct from those
      of other [2Fe-2S] ferredoxins. All hyperfine 1H resonances of the oxidized
      ferredoxin displayed anti-Curie temperature dependences. Reduced T. vaginalis
      ferredoxin displayed hyperfine resonances both upfield and downfield of the
      diamagnetic region. These resonances showed Curie temperature dependences.
      Overall the hyperfine-shifted NMR spectrum of T. vaginalis ferredoxin, along with
      other spectroscopic properties, suggested different structural properties for the
      active center of oxidized hydrogenosomal ferredoxins from those of other [2Fe-2S]
      ferredoxins.

PMID- 10065532
TI  - Interaction of Et2SnCl2 with 5'-IMP and 5'-GMP.
AB  - The interactions of Et2SnCl2 with 5'-IMP and 5'-GMP have been studied in aqueous
      solutions by 1H- and 31P-NMR spectroscopy as a function of pH. At low pH values
      (< 4.0) Sn(IV) interacts with the pyrophosphate oxygens of these nucleotides. At
      intermediate pH values (4-9.5) no interaction of the metal with the nucleotides
      take place, while at pH > 9.5 the sugar O'2 and O'3 atoms are the preferred
      coordination sites. In addition, the solid adducts obtained from aqueous
      solutions at pH = 3-4 of the above interactions correspond to formulae;
      (Et2Sn)2(5'-IMP)2(H2O) and (Et2Sn)3(5'-GMP)2(OH)2(H2O)2 as their elemental
      analysis show. IR spectra and solid state 13C, 31P-NMR spectra 119Sn Mossbauer
      and solution 119Sn-NMR spectra once more confirm the pyrophosphate involvement in
      bonding with Sn(IV) in oligomeric or polymeric structures and trigonal
      bipyramidal or octahedral geometries.

PMID- 10065533
TI  - Palladium and platinum famotidine complexes.
AB  - The molecule of the well-known ulceration inhibitor, famotidine, is an excellent
      coordinator of transition metal ions. The guanidine, amine group and thiazole
      nitrogen, and the thioether sulphur are preferential sites to bind metal ions.
      Pd(II) and Pt(II) derivatives of famotidine have been synthesized and studied
      structurally. There is evidence that the palladium complex is a monomer while the
      platinum complex forms a dimer. Due to the interesting structure of the platinum
      complex several assays have examined the possible antitumour activity. Changes in
      DNA conformation induced by both complexes have been detected by CD, interstrand
      crosslinking interactions and electrophoretic mobility, but studies of the
      cytotoxicity of the platinum compound with U937 human leukemia cells and HeLA
      human womb carcinoma cells show only a small antiproliferative potential.

PMID- 10065534
TI  - Electron paramagnetic resonance, kinetics of formation and decomposition studies
      of (bis(hydroxyethyl)amino-tris(hydroxymethyl)-methane)oxochromate(V): a model
      chromium(V) complex for DNA damage studies.
AB  - A new chromium complex, (bis(hydroxyethyl)amino
      tris(hydroxymethyl)methane)oxochromate(V), has been characterized by epr
      spectroscopy. The chromium(V) complex was formed by the ligand displacement
      reaction of bis(2-ethyl-2-hydroxybutanato) oxochromate(V) with
      bis(hydroxyethyl)amino-tris(hydroxy-methyl)methane (BT). Both epr and kinetic
      data indicate that the reaction proceeds through a chromium(V) intermediate.
      Kinetics of formation of the intermediate exhibit a rate saturation at higher
      [BT] (> 30 mM) indicating a rate law constituting an equilibrium between the
      parent Cr(V) complex and the bis-tris ligand followed by a pure first order
      process. The g-value of the intermediate is consistent with a Cr(V) complex in
      which the BT is coordinated in a bidentate fashion replacing a coordinated
      hydroxy butanoic acid ligand, affording a mixed ligand complex. The equilibrium
      step (K = 36 M-1) consists of monodentate coordination by the BT ligand and the
      limiting first order rate constant (1.9 x 10(-2) s-1) manifests the rate of
      chelation by the polydentate ligand. The intermediate is converted to the product
      upon further chelation through the complete displacement of the remaining 2-ethyl
      2-hydroxy butanoic acid by a first order process (k = 0.023 s-1). The epr data
      support a pair of products that are in rapid equilibrium. In these products, BT
      functions either as a tetra or a penta-dentate ligand coordinating through four
      or five alkoxy sites. The enthalpy and entropy of activations related to the two
      chelation steps were found to be 32 +/- 2 kJ/mol and -(1.7 +/- 0.2) x 10(2) J/mol
      K for the intermediate, and 36 +/- 1 kJ/mol and -(1.5 +/- 0.2) x 10(2) J/mol K
      for the product. Our data support an associative mechanism for the chelation
      steps. The Cr(V)-BT product is more stable than the parent complex. The second
      order disproportionation rate constant for the Cr(V)-BT complex was evaluated to
      be 0.1 M-1 s-1 compared to 8.0 M-1 s-1 for the parent complex. This is the first
      example of a chromium(V) complex with a non-macrocyclic ligand coordinating
      through oxygen donor atoms which is stable in aqueous solution at neutral pH over
      a long period of time.

PMID- 10065535
TI  - Palladium(II) complexes with N,N'-dialkyl-1,10-phenanthroline-2,9-dimathanamine:
      synthesis, characterization and cytotoxic activity.
AB  - Five new tetradentate ligands and their corresponding palladium complexes,
      [Pd(L)]Cl2 (L = N,N'-dimethyl-1,10-phenanthroline-2,9-dimathanamine, N,N'-diethyl
      1,10-phenanthroline-2,9-dimathanamine, N,N'-dipropyl-1,10-phenanthroline-2,9
      dimathanamine, N,N'-ditert-butyl-1,10-phenanthroline-2,9-dimathanamine, N,N'
      dicyclohexyl-1,10-phenanthroline-2,9-dimathanamine) have been synthesized. The
      ligands and their complexes have been characterized by elemental analysis, IR,
      and 1H NMR. The complexes have been assayed for antitumor activity in vitro
      against the mouse leukemia L1210 and the mouse liver carcinoma Bel7402 cell
      lines. The results showed that the activities of these complexes are
      significantly dependent on the nature of the alkyl groups on the coordinated
      amine moieties, and three of these palladium complexes showed lower ID50 values
      against the two cell lines than cisplatin.

PMID- 10065536
TI  - Concentration of Cu, EPR-detectable Cu, and formation of cupric-ferrocyanide in
      membranes with pMMO.
AB  - EPR spectra were obtained for the type 2 Cu(2+) site in particulate methane
      monooxygenase, pMMO, from membrane fractions of Methylomicrobium album BG8. In
      addition to the EPR signal with g parallel = 2.24 and A parallel = 185 G found in
      both cells and membrane fractions, a second EPR signal with g parallel = 2.29 and
      A parallel = 146 G was found in membrane fractions and attributed to oxidation of
      cuprous sites. Comparison of EPR-detectable Cu(2+) with total copper determined
      by atomic absorption suggests that there are two or three EPR-silent coppers for
      every EPR-detectable copper and that there are approximately four coppers per
      enzyme composed of the 47, 27, and 25 kDa subunits. Treatment of membrane
      fractions loaded with pMMO with Fe(CN)6(3-) results in a new EPR signal that is
      attributed to CuFe(CN)6(2-), not to an intrinsic trimeric copper cluster as
      previously reported in studies with a related bacterium.

PMID- 10065537
TI  - Binding properties and stoichiometries of a palladium(II) complex to
      metallothioneins in vivo and in vitro.
AB  - This paper will be the first to discuss the in vivo and in vitro properties of a
      Pd(II) complex, K2PdCl4, interacting with metallothioneins (MTs). In vivo
      experiments revealed that intraperitoneal injections of K2PdCl4 into rabbits led
      to the simultaneous synthesis of Pd-MT in the kidney and Zn7MT in the liver. The
      renal Pd-MT complex contains 3.6 +/- 0.3 Pd, 2.1 +/- 0.2 Zn, and 1.0 +/- 0.1 Cu
      per mole protein. It was found that pre-treatment with Zn(NO3)2 before K2PdCl4
      injections significantly enhanced renal Pd-MT level. The same pre-treatment also
      increases hepatic Zn-MT levels. These results strongly suggest that Pd(II) ions
      can be bound in vivo by MT existing in the rabbit kidneys to form Pd-MT. Gel
      filtration chromatographic studies after the incubation of either native
      Cd5Zn2MT2 or Zn7MT2 with K2PdCl4 in vitro demonstrate that Pd(II) ions promote
      the non-oxidative oligomerization of native MTs. Increasing the level of Pd(II)
      relative to MT led to a concomitant increase in the apparent yield of MT
      oligomers. At relatively low Pd-MT ratio, Pd(II) is found predominantly in the
      oligomers while the monomeric products are chiefly composed of the reactants,
      Cd5Zn2MT2 or Zn7MT2. Based on our experimental data, the mechanisms of the
      reactions between Pd(II) and MTs in vivo and in vitro are discussed.

PMID- 10065538
TI  - Spectroscopic and biological properties of palladium(II) complexes of ethyl 2
      quinolylmethylphosphonate.
AB  - Spectroscopic (1H NMR, UV-visible) and biological (cytostatic, antiviral
      activity) studies of palladium(II) complexes of monoethyl 2
      quinolymethylphosphonate (2-Hmqmp): dihalide adducts trans-Pd(2-Hmqmp)2X2,
      chelate Pd(2-mqmp)2.2H2O and ion-pair salt complexes [2-H2mqmp]+[Pd(2-Hmqmp)X3]-
      (X = Cl, Br), have been carried out in order to determine structural and
      biological properties of these biologically interesting complex compounds. The
      complexes were evaluated in vitro for their cytostatic activity against murine
      L1210 and human KB and T-lymphoblast Molt4/C8 and CEM/0 cell lines, and the
      results obtained were compared with those obtained for the complexes of diethyl 2
      quinolylmethylphosphonate (2-dqmp). The L1210 cell was the most responsive line
      and complexes of diester 2-dqmp were more active than complexes of monoester 2
      Hmqmp. A good relationship was observed between the cytostatic activity of the
      complexes and their lypophilicity or solubility. Some complexes exhibited
      significant cell growth inhibitory effects, but none of the them was more
      cytostatic than cisplatin. Both 2-dqmp and 2-Hmqmp complexes were also evaluated
      in vitro for their antiviral activity in different assay systems, comprising a
      broad spectrum of DNA and RNA viruses, but no specific antiviral effects were
      noted. In addition, the complexes did not show any specific anti-HIV activity.

PMID- 10065539
TI  - Glucose-induced period-doubling cascade in the electrical activity of pancreatic
      beta-cells.
AB  - In the presence of stimulatory concentrations of glucose, the membrane potential
      of pancreatic beta-cells may experience a transition from periods of rapid spike
      like oscillations alternating with a pseudo-steady state to spike-only
      oscillations. Insulin secretion from beta-cells closely correlates the periods of
      spike-like oscillations. The purpose of this paper is to study the mathematical
      structure which underlines this transitional stage in a pancreatic beta-cell
      model. It is demonstrated that the transition can be chaotic but becomes more and
      more regular with increase in glucose. In particular, the system undergoes a
      reversed period-doubling cascade leading to the spike-only oscillations as the
      glucose concentration crosses a threshold. The transition interval in glucose
      concentration is estimated to be extremely small in terms of the rate of change
      for the calcium dynamics in the beta-cells. The methods are based on the theory
      of unimodal maps and the geometric and asymptotic theories of singular
      perturbations.

PMID- 10065540
TI  - Genetic analysis of the population structure of socially organized oystercatchers
      (Haematopus ostralegus) using microsatellites.
AB  - On the island of Schiermonnikoog (The Netherlands), the breeding population of
      oystercatchers can be divided into two groups: 'residents' and 'leapfrogs', based
      on their distinct social characteristics and limited probabilities of status
      change between breeding seasons. In order to investigate whether this social
      organization has caused local genetic differentiation, leapfrogs and residents
      were compared at eight polymorphic microsatellite loci. No significant genetic
      subdivision between residents and leapfrogs was observed (theta = 0.0000; 95%
      confidence interval (CI), -0.0027-0.0033), indicating that the oystercatcher
      population on the island of Schiermonnikoog has to be considered as one panmictic
      unit. Investigation of three additional locations in the northern part of The
      Netherlands did not reveal significant genetic population subdivision either
      (theta = -0.0005; 95% CI, -0.0045-0.0037), despite the fact that adult
      osytercatchers show extreme fidelity to their breeding localities. These results
      indicate panmixis and considerable levels of gene flow within the northern part
      of The Netherlands. Thus, the results from genetical analyses do not seem to be
      in agreement with observational data on the dispersal behaviour of breeding
      individuals. It is argued that the lack of population structure, locally on
      Schiermonnikoog as well as across larger geographical distances, is to be
      attributed to high levels of gene flow through dispersal of juvenile birds.

PMID- 10065541
TI  - Mitochondrial DNA population structure of roan and sable antelope: implications
      for the translocation and conservation of the species.
AB  - Mitochondrial DNA (mtDNA) control region sequences were analysed to determine the
      geographical genetic structure of Hippotragus niger (sable antelope) and H.
      equinus (roan antelope). Analyses by AMOVA, minimum evolution networks,
      parsimony, neighbour joining and maximum likelihood show that the roan antelope
      populations are geographically partitioned and that their phylogeography
      corresponds well with subspecific boundaries. In sharp contrast, however, our
      sequence data group all the sable antelope into two well-delineated maternal
      clades. One comprising specimens from the strictly east African H.n. roosevelti,
      and a second geographically diverse group which includes H.n. niger (South
      Africa, Zimbabwe), H.n. variani (Angola), and H.n. Kirkii (Zambia, Malawi). The
      differences in the genetic population structure suggest that distinct extrinsic
      and intrinsic factors have shaped the phylogeography of these two closely related
      antelope species. In the absence of obvious extrinsic barriers to gene flow, we
      suggest that behavioural differences may be responsible, at least in part, for
      the contrasting spatial patterns detected among geographical localities. Although
      our data reflect only the maternal phylogeny of these important game species,
      they nonetheless suggest that different management strategies should be applied.
      We recommend that roan antelope be translocated only within the currently defined
      subspecies boundaries, while in the case of sable antelope, conservation measures
      should focus on preserving the genetic integrity of the east African and southern
      African sable populations. Implicit in this is that translocations of animals
      between populations comprising these two distinct maternal genetic clades should
      be actively discouraged.

PMID- 10065542
TI  - Mutability of microsatellites developed for the ant Camponotus consobrinus.
AB  - Five highly polymorphic (GA)n microsatellite loci are reported for the formicine
      ant Camponotus consobrinus. The occurrence of many nests with a simple family
      structure enabled a search for new mutations, 11 of which were found from 3055
      informative typings. These mutations were not randomly distributed across loci,
      10 of them occurring at the locus Ccon70. The spectrum of mutations across
      alleles at Ccon70 was also nonrandom, with all of them occurring in alleles in
      the upper half of the allele size distribution. Six of the Ccon70 mutations
      decreased allele size. The mutations observed fit the stepwise mutation model
      well, i.e. mutations could always be assigned to an allele which differed in size
      from them by one repeat unit. The parental origins of the Ccon70 mutations were
      established and appear more female biased than vertebrate mutations,
      significantly so compared with human haemophilia A and primate intron mutations.
      This result may indicate that the lack of meiosis in males (which are haploid in
      ants) reduces the mutation rate in that sex relative to species in which both
      sexes are diploid.

PMID- 10065543
TI  - Mitochondrial and ribosomal internal transcribed spacer (ITS2) diversity of the
      African malaria vector Anopheles funestus.
AB  - The pattern of sequence variation in the mitochondrial DNA cytochrome b gene (cyt
      b) and ribosomal DNA internal transcribed spacer 2 (ITS2) was examined in
      Anopheles funestus from Senegal and Burkina Faso in West Africa and Kenya in East
      Africa. From both West African countries, samples included individuals
      hypothesized to represent reproductively isolated taxa based upon different
      karyotypes and behaviours. Analysis of the cyt-b data revealed high haplotypic
      diversity (86%) and an average pairwise difference per site of 0.42%. Sequence
      variation was not partitioned by geographical origin or karyotype class. The most
      common haplotype was sampled across Africa (approximately 6000 km). Analysis of
      the ITS2 data revealed one of the longest spacers yet found in anophelines
      (approximately 704 bp). In common with other anopheline ITS2 sequences, this one
      had microsatellites and frequent runs of individual nucleotides. Also in common
      with data from other anopheline ITS2 studies, the An. funestus sequences were
      almost monomorphic, with only two rare polymorphisms detected. The results from
      both markers are congruent and do not support the hypothesis of reproductively
      isolated chromosomal taxa within An. funestus. Whether the lack of support by
      mitochondrial DNA (mtDNA) and ribosomal DNA (rDNA) sequences is a result of the
      recent origin of the presumptive taxa, or of the absence of barriers to gene
      flow, remains to be elucidated, using more rapidly evolving markers such as
      microsatellites.

PMID- 10065544
TI  - Fine-scale genetic structuring in a natural population of European wild rabbits
      (Oryctolagus cuniculus).
AB  - The genetic structure of a free-living tagged population of European wild rabbits
      (Oryctolagus cuniculus) was investigated for two consecutive years (1990 and
      1991) using 10 polymorphic microsatellite loci. A specific social behaviour, the
      formation of stable breeding groups, influenced the genetic structure of the
      population. These breeding groups were shown to constitute genetically
      differentiated units with low levels of gene flow between them. The average
      relatedness among members of a social group was higher than within the population
      as a whole. As a result of female philopatry coupled with male-biased natal
      dispersal, the relatedness of females was higher than that of males, both within
      social groups and in the whole population. Furthermore, the average relatedness
      of females within groups was twice the relatedness of females between groups.
      This study reveals marked fine-scale, intrapopulation genetic structure, which is
      attributable to the social behaviour of the European wild rabbit.

PMID- 10065545
TI  - Molecular variation in Leymus species and populations.
AB  - Icelandic populations of European lymegrass [Leymus arenarius (L.) Hochst.] were
      examined using amplified fragment length polymorphism (AFLP) and restriction
      fragment length polymorphism (RFLP) of the major ribosomal genes (18S-5.8S-26S
      rDNA), in comparison with Alaskan populations of its closely related species L.
      mollis (Trin.) Pilger. The AFLP profiles emerged as two distinct entities,
      clearly separating the two species, and based on species-specific bands it was
      simple to distinguish these two morphologically similar species. The rDNA-RFLPs
      also differentiated the species. Within species, the Icelandic L. arenarius was
      more homogeneous than the Alaskan L. mollis, and its variation was dispersed over
      geographically different populations, suggesting a common gene pool. The
      variation among the Alaskan L. mollis was more extensive and its interrupted
      pattern may be the result of gene introgression at subspecies level. Within a 40
      year-old population of L. mollis established in Iceland from Alaskan material,
      the molecular profiles separated old and new genotypes. Both AFLP and rDNA
      revealed the new genotypes to be extremely similar. This rapid change in allele
      frequency is thought to be the result of adaptation to a new environment.

PMID- 10065546
TI  - Microsatellite loci in eelgrass Zostera marina reveal marked polymorphism within
      and among populations.
AB  - Using an enriched genomic library, we developed seven (CT)n/(GA)n microsatellite
      loci for eelgrass Zostera marina L. Enrichment is described and highly
      recommended for genomes in which microsatellites are rare, such as in many
      plants. A test for polymorphism was performed on individuals from three
      geographically separated populations (N = 15/population) and revealed
      considerable genetic variation. The number of alleles per locus varied between
      five and 11 and the observed heterozygosities for single loci ranged from 0.16 to
      0.81 within populations. Mean allele lengths were markedly different among
      populations, indicating that the identified loci will be useful in studying
      population structure in Z. marina. As the frequency of the most abundant
      multilocus genotype within populations was always < 1%, these loci have
      sufficient resolving power to address clone size in predominantly vegetatively
      reproducing populations.

PMID- 10065547
TI  - A preliminary examination of genetic variation in a peripheral population of
      Blanding's turtle, Emydoidea blandingii.
AB  - Random amplified polymorphic DNA (RAPD) was used to compare the Nova Scotia
      population of Blanding's turtle (Emydoidea blandingii) with several populations
      from the species' main range. The Nova Scotia population is believed to have been
      isolated from the main range for 4000-8000 years. Cluster analysis using a
      neighbour-joining algorithm produced a dendrogram showing the Nova Scotia
      population clustering separately from those populations in the main range.
      Analysis of molecular variance shows 34.28% of total variance to be accounted for
      between the Nova Scotia population and populations in the main range. While this
      study is preliminary, the results suggest that the Nova Scotia population of
      Blanding's turtle may be important to the maintenance of genetic diversity in the
      species.

PMID- 10065548
TI  - Microgeographic population genetic structure in the northern water snake, Nerodia
      sipedon sipedon detected using microsatellite DNA loci.
AB  - We describe the isolation and genetic characterization of eight microsatellite
      DNA loci from the northern water snake, Nerodia sipedon sipedon and use these
      loci to analyse levels of genetic differentiation between local (< 2 km apart)
      populations of these snakes in Ontario. These loci are variable, with expected
      heterozygosities ranging from 0.28 to 0.91, and can correctly exclude nonsires in
      parentage analyses with a high probability (0.998). Population analyses reveal
      significant deviation from expected heterozygosity levels for one population,
      probably a result of a null allele(s) at a single locus and small but significant
      levels of genetic differentiation among all three populations. This demonstrates
      that microgeographic genetic structure exists in this species, possibly due to
      limited dispersal.

PMID- 10065549
TI  - Development and characterization of microsatellite markers in Camellia japonica
      L.

PMID- 10065550
TI  - Microsatellites in walleye Stizostedion vitreum.

PMID- 10065551
TI  - Isolation and characterization of microsatellites in albatrosses.

PMID- 10065552
TI  - Polymorphic microsatellite loci identified in the highly clonal freshwater
      bryozoan Cristatella mucedo.

PMID- 10065553
TI  - Isolation and characterization of microsatellite loci from the three-spined
      stickleback (Gasterosteus aculeatus L.).

PMID- 10065554
TI  - Identification and characterization of microsatellite loci in coconut (Cocos
      nucifera L.) and the analysis of coconut populations in Sri Lanka.

PMID- 10065555
TI  - Novel genes induced during an arbuscular mycorrhizal (AM) symbiosis formed
      between Medicago truncatula and Glomus versiforme.
AB  - Many terrestrial plant species are able to form symbiotic associations with
      arbuscular mycorrhizal fungi. Here we have identified three cDNA clones
      representing genes whose expression is induced during the arbuscular mycorrhizal
      symbiosis formed between Medicago truncatula and an arbuscular mycorrhizal
      fungus, Glomus versiforme. The three clones represent M. truncatula genes and
      encode novel proteins: a xyloglucan endotransglycosylase-related protein, a
      putative arabinogalactan protein (AGP), and a putative homologue of the mammalian
      p110 subunit of initiation factor 3 (eIF3). These genes show little or no
      expression in M. truncatula roots prior to formation of the symbiosis and are
      significantly induced following colonization by G. versiforme. The genes are not
      induced in roots in response to increases in phosphate. This suggests that
      induction of expression during the symbiosis is due to the interaction with the
      fungus and is not a secondary effect of improved phosphate nutrition. In situ
      hybridization revealed that the putative AGP is expressed specifically in
      cortical cells containing arbuscules. The identification of two mycorrhiza
      induced genes encoding proteins predicted to be involved in cell wall structure
      is consistent with previous electron microscopy data that indicated major
      alterations in the extracellular matrix of the cortical cells following
      colonization by mycorrhizal fungi.

PMID- 10065558
TI  - Mutation in GDP-fucose synthesis genes of Sinorhizobium fredii alters Nod factors
      and significantly decreases competitiveness to nodulate soybeans.
AB  - We mutagenized Sinorhizobium fredii HH103-1 with Tn5-B20 and screened about 2,000
      colonies for increased beta-galactosidase activity in the presence of the
      flavonoid naringenin. One mutant, designated SVQ287, produces
      lipochitooligosaccharide Nod factors (LCOs) that differ from those of the
      parental strain. The nonreducing N-acetylglucosamine residues of all of the LCOs
      of mutant SVQ287 lack fucose and 2-O-methylfucose substituents. In addition,
      SVQ287 synthesizes an LCO with an unusually long, C20:1 fatty acyl side chain.
      The transposon insertion of mutant SVQ287 lies within a 1.1-kb HindIII fragment.
      This and an adjacent 2.4-kb HindIII fragment were sequenced. The sequence
      contains the 3' end of noeK, nodZ, and noeL (the gene interrupted by Tn5-B20),
      and the 5' end of nolK, all in the same orientation. Although each of these genes
      has a similarly oriented counterpart on the symbiosis plasmid of the broad-host
      range Rhizobium sp. strain NGR234, there are significant differences in the
      noeK/nodZ intergenic region. Based on amino acid sequence homology, noeL encodes
      GDP-D-mannose dehydratase, an enzyme involved in the synthesis of GDP-L-fucose,
      and nolK encodes a NAD-dependent nucleotide sugar epimerase/dehydrogenase. We
      show that expression of the noeL gene is under the control of NodD1 in S. fredii
      and is most probably mediated by the nod box that precedes nodZ. Transposon
      insertion into neoL has two impacts on symbiosis with Williams soybean:
      nodulation rate is reduced slightly and competitiveness for nodulation is
      decreased significantly. Mutant SVQ287 retains its ability to form nitrogen
      fixing nodules on other legumes, but final nodule number is attenuated on Cajanus
      cajan.

PMID- 10065559
TI  - A novel 53-kDa nodulin of the symbiosome membrane of soybean nodules, controlled
      by Bradyrhizobium japonicum.
AB  - A nodule-specific 53-kDa protein (GmNOD53b) of the symbiosome membrane from
      soybean was isolated and its LysC digestion products were microsequenced. cDNA
      clones of this novel nodulin, obtained from cDNA library screening with an RT-PCR
      (reverse-transcriptase polymerase chain reaction)-generated hybridization probe
      exhibited no homology to proteins identified so far. The expression of GmNOD53b
      coincides with the onset of nitrogen fixation. Therefore, it is a late nodulin.
      Among other changes, the GmNOD53b is significantly reduced in nodules infected
      with the Bradyrhizobium japonicum mutant 184 on the protein level as well as on
      the level of mRNA expression, compared with the wild-type infected nodules. The
      reduction of GmNOD53b mRNA is related to an inactivation of the sipF gene in B.
      japonicum 184, coding for a functionally active signal peptidase.

PMID- 10065560
TI  - The nolL gene from Rhizobium etli determines nodulation efficiency by mediating
      the acetylation of the fucosyl residue in the nodulation factor.
AB  - The nodulation factors (Nod factors) of Rhizobium etli and R. loti carry a 4-O
      acetyl-L-fucosyl group at the reducing end. It has been claimed, based on
      sequence analysis, that NolL from R. loti participates in the 4-O-acetylation of
      the fucosyl residue of the Nod factors, as an acetyl-transferase (D. B. Scott, C.
      A. Young, J. M. Collins-Emerson, E. A. Terzaghi, E. S. Rockman, P. A. Lewis, and
      C. E. Pankhurst. Mol. Plant-Microbe Interact. 9:187-197, 1996). Further support
      for this hypothesis was obtained by studying the production of Nod factors in an
      R. etli nolL::Km mutant. Chromatographic and mass spectrometry analysis of the
      Nod factors produced by this strain showed that they lack the acetyl-fucosyl
      substituent, having a fucosyl group instead. Acetyl-fucosylation was restored
      upon complementation with a wild-type nolL gene. These results indicate that the
      nolL gene determines 4-O-acetylation of the fucosyl residue in Nod factors.
      Analysis of the predicted NolL polypeptide suggests a transmembranal location and
      that it belongs to the family of integral membrane transacylases (J. M. Slauch,
      A. A. Lee, M. J. Mahan, and J. J. Mekalanos. J. Bacteriol. 178:5904-5909, 1996).
      NolL from R. loti was also proposed to function as a transporter; our results
      show that NolL does not determine a differential secretion of Nod factors from
      the cell. We also performed plant assays that indicate that acetylation of the
      fucose conditions efficient nodulation by R. etli of some Phaseolus vulgaris
      cultivars, as well as of an alternate host (Vigna umbellata).

PMID- 10065561
TI  - Comparison of characteristics of the nodX genes from various Rhizobium
      leguminosarum strains.
AB  - We have analyzed the nucleotide sequences of the nodX genes from two strains of
      Rhizobium leguminosarum bv. viciae able to nodulate Afghan peas (strains A1 and
      Himalaya) and from two strains of R. leguminosarum bv. trifolii (ANU843 and CSF).
      The nodX genes of strains A1 and ANU843 were shown to be functional for the
      induction of nodules on Afghan peas. To analyze the cause of phenotypic
      differences of strain A1 and strain TOM we have studied the composition of the
      lipochitin-oligosaccharides (LCOs) produced by strain A1 after induction by the
      flavonoid naringenin or various pea root exudates. The structural analysis of the
      LCOs by mass spectrometry revealed that strain A1 synthesizes a family of at
      least 23 different LCOs. The use of exudates instead of naringenin resulted only
      in quantitative differences in the ratios of various LCOs produced.

PMID- 10065562
TI  - Anesthesia by the pediatric specialist.
AB  - There is increasing evidence that involvement of pediatric anesthesiologists in
      the perioperative care of infants and children can positively impact outcome.
      Considerable data have emerged in the past several years that clearly show that
      infants and small children experience untoward events at a much higher rate than
      do older children and adults. Herein the author presents some of this literature
      as well as data suggesting that anesthesiologists with interest and additional
      training in the care of infants and children can improve anesthesia outcomes.
      Even in these days of cost containment, it makes sense to provide the best
      pediatric team to care for the pediatric patient during the perioperative
      experience.

PMID- 10065563
TI  - Newer drugs in pediatric anesthesia.
AB  - Recent developments in pharmacology have offered new and broader options to the
      anesthesiologist caring for pediatric patients. Many new drugs do not have
      specific indications for use in the pediatric population, but clinical studies
      have examined the utility and cost-effectiveness of some of these agents.
      Information is presented on drugs used for premedication, induction, and
      maintenance of anesthesia. The clinical pharmacology of several new
      nondepolarizing muscle relaxants, and the recent controversy with regard to the
      use of succinylcholine also are presented. New drugs used in topical and regional
      anesthesia as well as options for anti-emetic therapy are discussed.

PMID- 10065564
TI  - Assessment of pediatric patients for general anesthesia: the child with an upper
      respiratory infection and the ex-premature infant.
AB  - There are two types of patients that commonly lead surgeons and anesthesiologists
      into discussions relating to the possible cancellation or postponement of a minor
      pediatric surgical procedure; the child with a recent upper respiratory
      infection, and the patient who was born prematurely. Current opinion of the risks
      of anesthesia in such patients and the factors that influence perioperative
      course are reviewed, and a plan of management is suggested.

PMID- 10065565
TI  - Perioperative alimentation in pediatric patients: when to stop, when to start,
      and what to give.
AB  - The first steps to liberalize NPO guidelines began in the early 1980s and were
      based more on compassion than science. Infants were allowed to be awakened at
      0300 and given clear liquids. Children whose anticipated surgical start times
      were later than 1200 were allowed to consume clear liquids at 0500. Fortunately,
      during the past decade, prospective double-blind NPO studies have been performed
      to provide more scientific input into the development of more humane and rational
      pediatric NPO guidelines. In this article the author reviews the historical
      aspects of aspiration pneumonitis, describes the significant findings of recent
      landmark studies, and presents the NPO guidelines recently promulgated by the
      Canadian Anaesthetists' Society.

PMID- 10065566
TI  - Postoperative complications and unanticipated hospital admissions.
AB  - Following anesthesia and surgery, children have more postoperative complications
      in the recovery room than adults. The majority of events are age-related
      (neonates and infants) and involve the respiratory rather than the cardiovascular
      system. In spite of newer antinausea drugs, pediatric patients have a high
      incidence of postoperative nausea and vomiting leading to unexpected admission to
      the hospital. Pain is underreported and undertreated in the pediatric population.

PMID- 10065567
TI  - Blocks and other techniques pediatric surgeons can employ to reduce postoperative
      pain in pediatric patients.
AB  - Painful experiences, such as circumcision without the benefit of anesthesia,
      during the neonatal period may induce lifelong behavior changes in infants and
      children. By inference, this is probably true for other painful experiences
      encountered during childhood. It is much easier to prevent the establishment of
      pain than it is to eradicate it once it has become firmly established. As
      "captain of the ship," there are three very basic things a pediatric surgeon can
      do to reduce postoperative discomfort in your young patients. First, whenever
      possible, allow caudal blocks or other forms of regional anesthesia, such as
      penile or ilioinguinal-iliohypogastric nerve blocks, to be performed on your
      patients. Second, always use timed analgesics and avoid PRN orders. Last, know
      how to use two analgesics well, one narcotic and one non-narcotic. Be completely
      familiar with their uptake, distribution, and elimination half-lives. This
      article presents a review of the efficacy and safety of caudal blocks, and the
      use of ilioinguinal/iliohypogastric, "splash," and penile blocks as alternative
      techniques for providing perineal analgesia. In addition, the most current and
      efficacious dosage regimen for the rectal administration of acetaminophen (40.0
      mg/kg after induction of anesthesia, then 20.0 mg/kg every 6 hours for the first
      24 postoperative hours) is presented. Additionally, the novel use of intravenous
      methadone (0.2 to 0.3 mg/kg) to provide intense and protracted narcotic analgesia
      is discussed.

PMID- 10065568
TI  - Sedation and anesthesia outside the operating room: answers to common questions.
AB  - In recent years, practitioners have recognized the importance of providing
      comfort to children and have increased their use of analgesics and anxiolytics
      during painful medical procedures. In this article, the author reviews commonly
      asked questions regarding administering sedation to children for painful
      procedures outside the operating room. Current safety guidelines are reviewed, as
      well as qualifications of personnel performing sedations, contraindications to
      sedation, fasting guidelines before sedation, and common sedation techniques.

PMID- 10065569
TI  - Sharing the pediatric airway: issues between the surgeon and the
      anesthesiologist.
AB  - During surgical procedures, "ownership" of the patient's airway is often
      controversial. Communication between the anesthesiologist and the surgeon is
      critical. The author discusses several medical scenarios in which the
      anesthesiologist and surgeon must share the patient's airway. Strategies are
      outlined that can be used by both surgeon and anesthesiologist to ensure optimal
      outcome for patients.

PMID- 10065570
TI  - Raising eyebrows: problems that get anesthesiologists' attention.
AB  - There are many clinical situations of concern that may be unique to pediatric
      anesthesiologists. The author discusses four of the more common presentations:
      asthma, cystic fibrosis, anterior mediastinal masses, and latex allergy. Many
      such issues can be resolved before surgery by consultation with members of the
      operating team. Some issues may require additional input from nonsurgical
      pediatric specialists. By maintaining good communication between the
      anesthesiologist and the surgeon, delays and cancellations can be minimized and
      patient care enhanced.

PMID- 10065571
TI  - Increase in obesity.

PMID- 10065572
TI  - Bariatric surgical utterances: need they be dogmatic?

PMID- 10065573
TI  - Selected topics in malpractice reduction in bariatric and other surgery.
AB  - On the basis of an extensive legal experience, the sound strategies that prevent
      or reduce malpractice litigation in bariatric or other surgery are presented.

PMID- 10065574
TI  - Complications following Swedish adjustable gastric banding: a long-term follow
      up.
AB  - BACKGROUND: The Swedish adjustable gastric band (SAGB) has been in use since
      1985. The aim of this study was to analyze short and long-term complications
      linked to the SAGB. MATERIALS AND METHODS: Between August 1990 and December 1996,
      we operated on a series of 326 patients (78 men and 248 women) at the Huddinge
      University Hospital and the Norra Alvsborg County Hospital. The mean age of
      patients at surgery was 40 years (range 19-62). The mean preoperative weight was
      125 kg (range 81-181). The mean excess weight was 80%. RESULTS: The mean time of
      follow-up was 28 months (range 6-76). Complications requiring reoperation
      included two (0.6%) band dislocations, six (1.8%) band leakages, and 16 (4.6%)
      band migrations-erosions. The most common reason for abdominal reoperation, band
      migration, was attributed to overfilling of the band system. In the patients in
      whom migration occurred, the bands had been filled with a mean volume of 12.6 ml
      fluid. In the remaining patients, the mean volume was 8.7 ml. The most common
      complication not requiring reoperation was reflux disease (4.7%). In cases with a
      small pouch, this complication did not seem to be a serious problem. The mean
      excess weight loss in the 296 patients without complications was 68%. CONCLUSION:
      The overall long-term complication rate following SAGB is reasonable. With
      improved operating technique and closer follow-up, it should be possible to
      reduce the complication rate further. Reoperation because of band migration
      appears to be related to overfilling of the system and should therefore be
      avoidable in most cases.

PMID- 10065575
TI  - Iron absorption and therapy after gastric bypass.
AB  - BACKGROUND: Iron deficiency anemia is a common complication of gastric bypass.
      The authors assessed the value of taking vitamin C with oral iron in correcting
      deficiencies in iron stores and anemia postoperatively. MATERIALS AND METHODS:
      Iron absorption tests were performed on 55 patients 3.2+/-2.0 years after
      isolated gastric bypass to identify those at higher risk for the late development
      of anemia. Twenty-nine of this group agreed to a therapeutic trial of iron alone
      or with vitamin C over a 2-month period. All 55 patients were followed up for
      27.1+/-1.0 months following the study. RESULTS: The iron absorption test
      identified patients with low iron stores, as indicated by low serum ferritin, and
      those with sufficient absorption surface to benefit from oral iron. The addition
      of vitamin C appears to enhance the therapeutic effect of iron by correcting
      ferritin deficits (P < 0.01) and anemia (P < 0.05). Differences in intestine
      length bypassed by the operation (10 vs. 100 cm) did not affect late ferritin and
      hemoglobin values. CONCLUSION: This study suggests but does not prove that the
      addition of vitamin C to iron therapy after gastric bypass is more effective in
      restoring ferritin and hemoglobin than iron alone. These results are in contrast
      with the outcome 22.8 months later, when approximately 50% of study patients were
      again anemic. Closer follow-up of patients is urgently needed.

PMID- 10065576
TI  - Gastro-gastric fistulas and marginal ulcers in gastric bypass procedures for
      weight reduction.
AB  - BACKGROUND: Gastro-gastric fistulas and marginal ulcers are frequent and serious
      complications of gastric compartmentalization procedures for obesity. METHODS:
      The authors analyzed 810 patients after 911 operations for gastro-gastric
      fistulas and marginal ulcers over an 8-year period. All patients underwent a form
      of gastric bypass, in which a pouch is constructed along the lesser curvature of
      the stomach. The outlet of the pouch was restricted with a prosthetic band. In
      the first 189 patients (Group I), the pouch and stomach were stapled in
      continuity or partially divided. In the next 222 patients (Group II), segments
      were stapled and separated by transection. In the remaining 492 cases (Group
      III), in addition to transection of the stomach, a limb of jejunum was interposed
      between the pouch and excluded stomach. Stapled anastomoses were done in Group I
      and II patients and a portion of Group III patients. The remaining patients
      underwent hand-sewn anastomosis. RESULTS: Gastro-gastric fistulas occurred in 49%
      of the patients in Group I, 2.6% of those in Group II, and 0% of those in Group
      III. In stapled anastomosis, the incidence of marginal ulceration in Groups I,
      II, and III were 8.5%, 5.4%, and 5.1%, respectively. In a subset of Group III
      patients, in whom a two-layer, hand-sewn anastomosis was done, the incidence was
      1.6% when the outer layer was not absorbable and 0% when both layers were
      absorbable. CONCLUSIONS: Gastro-gastric fistulas and marginal ulcerations are
      likely the result of breakdown of the mucosa resulting from migrating staples and
      other foreign material. Lack of integrity of the gastric lining facilitates the
      action of the gastric digestive process. Transection of gastric segments with
      interposition of jejunum prevents gastro-gastric fistula formation. An intact
      serosa appears to block the digestion of bowel wall by gastric enzymes. Our early
      data suggest that the use of absorbable sutures at the gastrojejunostomy
      significantly decreases the incidence of marginal ulceration.

PMID- 10065577
TI  - Vertical banded gastroplasty-gastric bypass with and without the interposition of
      jejunum: preliminary report.
AB  - BACKGROUND: The complications of the gastric pouch in gastric bypass surgery are
      well known. Since the first report of this surgery 30 years ago, new technical
      aspects that make it safer and more effective have been implemented. METHODS: As
      a modification of gastric bypass, the authors have performed 305 vertical banded
      gastroplasty-gastric bypass procedures. Two groups of patients underwent the
      procedure: Group I (n = 206) without a limb of jejunum interposed between the
      gastric pouch and the excluded stomach, and Group II (n = 99) with a limb of
      jejunum interposed between the pouch and the stomach. The results regarding
      excess weight loss and complications of the gastric pouch during the first year
      after surgery were compared. RESULTS: Age, sex, initial weight, body mass index,
      and percentage of ideal weight were similar in both groups. Excess weight loss
      was also similar. The complications in Group I were 1 leak, 3 left subphrenic
      abscesses, 2 erosive gastritis with bleeding, 1 stenosis of the
      gastrojejunostomy, 1 perforated ulcer, and 4 marginal ulcers with bleeding. Two
      patients in Group II developed bleeding from the staple-line. CONCLUSIONS: These
      preliminary data suggest that complications of the gastric pouch can be reduced
      by interposing a limb of jejunum between the pouch and the excluded stomach. This
      is an early experience; long-term results are pending.

PMID- 10065578
TI  - Patient satisfaction and results of vertical banded gastroplasty and gastric
      bypass.
AB  - BACKGROUND: Morbid obesity contributes to many health risks, including physical,
      emotional, and social problems. Various surgical treatments for morbid obesity
      have developed and have so far met with good results. This study compares
      vertical banded gastroplasty (VBG) with gastric bypass (GBP) and the patients'
      satisfaction with either procedure. METHODS: Between April 1993 and July 1997, 63
      bariatric surgical procedures were performed at Eisenhower Army Medical Center.
      Of those, complete follow-up was obtained for 29 patients. The parameters
      evaluated included age, preoperative and postoperative weights, body mass index
      (BMI), type of surgery, complications, and the patient's level of satisfaction.
      RESULTS: The study group consisted of 27 women and 2 men. The average
      preoperative weight was 135 kg, and the average preoperative BMI was 48.3 kg/m2.
      There were 17 VBGs and 12 GBPs performed. The average total weight loss was 45.1
      kg. The average postoperative BMI was 33.2 kg/m2. There were no statistically
      significant differences in weight loss between VBG and GBP. Four of 17 patients
      had complications after VBG, and three of 12 patients had complications after
      GBP. After VBG, 94.1 % of patients were satisfied, and after GBP, 100% were
      satisfied. Twenty-seven of 28 patients stated that they would have the surgery
      again. CONCLUSION: There were no statistically significant differences in weight
      loss or complications after VBG or GBP. Patient satisfaction was high after both
      procedures. Therefore, bariatric surgery is important in the treatment of
      appropriately selected, morbidly obese patients.

PMID- 10065579
TI  - Orally administered ranitidine plasma concentrations before and after
      biliopancreatic diversion in morbidly obese patients.
AB  - BACKGROUND: Patients undergoing biliopancreatic diversion (BPD) may develop
      gastric ulcers, particularly within the first postoperative year. The
      prophylactic use of antisecretory compounds at the usual therapeutic doses,
      mainly conventional H2-receptor antagonists such as ranitidine, may reduce the
      incidence of this complication, which occurs in approximately 5% of patients
      after BPD. METHODS: The authors measured the plasma concentrations of ranitidine
      (300 mg orally) in obese patients, before and 8 months after BPD, and in control
      subjects of normal weight. The study included 11 obese patients undergoing BPD
      (age 45+/-14 years; preoperative and postoperative weights 124+/-21 and 92+/-11
      kg) and 10 normal-weight subjects (age 37+/-13 years, weight 67+/-9 kg). RESULTS:
      Postoperative ranitidine plasma concentrations showed only minor differences from
      preoperative levels, with slightly higher maximum concentrations occurring
      sooner. The mean area under the curve was on the average 30% higher than
      preoperatively. All parameters, however, were similar to those in control
      subjects. CONCLUSIONS: BPD per se does not greatly affect the pharmacokinetic
      behavior of ranitidine, and therefore a conventional dosage regimen appears
      adequate for the prophylaxis and therapy of gastric ulcers associated with this
      operation.

PMID- 10065580
TI  - Obesity surgery in Russia.
AB  - BACKGROUND: In Russia, 40% of the population are overweight, and 26% are obese.
      As was mentioned at the IFSO Symposium in Cancun, very little is known about
      obesity surgery in Russia. METHODS: The authors undertook a literature search and
      interviewed surgeons who are known to perform bariatric procedures. RESULTS:
      Jejunoileal bypass (JIB) was used in the 1970s but has been abandoned by most
      surgeons. Since 1977, 334 JIBs, of a total of 360 bariatric operations, have been
      performed at I Saint Petersburg Medical University. The remaining 26 operations
      included 14 gastric bandings, 6 horizontal and 4 vertical gastroplasties, and 2
      gastric bypasses. Since 1984, 545 gastric banding procedures have been done at
      the Moscow Medical Academy, where the current approach is the lap-band type of
      gastric banding. The laparoscopic technique of adjustable gastric banding is
      beginning to be used. Vertical banded gastroplasty (VBG) was begun in the early
      1990s. At the Russian Research Center of Surgery in Moscow, 48 Mason VBGs have
      been done. The other group in Moscow reported 28 VBGs without the creation of a
      window and including covering the stoma by polypropylene mesh. There are only a
      few known cases of gastric bypass procedures. No data on biliopancreatic
      diversion were found. CONCLUSIONS: Obesity surgery is not being performed enough
      to satisfy the requirements of the Russian population. Simple operations are more
      common than complex ones. The use of the laparoscopic approach has begun and
      probably will increase.

PMID- 10065581
TI  - Endoscopic threaded imaging port (EndoTIP) for laparoscopy: experience with
      different body weights.
AB  - BACKGROUND: A laparoscopic access system was developed for primary port
      insertion. The cannula requires no trocar and no axial penetration force during
      insertion. It provides magnified visualization through the scope on the monitor
      during access and exit. The device has a proximal valve section and a distal
      cannula section with a single thread winding around its outer surface, ending in
      a blunt tip. After umbilical incision and Veress insufflation, a 0 degrees
      laparoscope is mounted in the cannula. The tip of the cannula is inserted into a
      tiny fascial incision and rotated clockwise. The fascia and then the muscle
      fibers spread radially and are transposed onto the cannula's outer thread. The
      thin peritoneum transilluminates; bowel, vessels, and/or adhesions are visualized
      before entry into the peritoneum. METHODS: The cannula was used in 234
      consecutive patients: 8.1% were markedly obese, with a body mass index (BMI) > or
      =35, 14.8% were moderately obese (BMI 30 to <35), and 77.1% were mildly obese or
      normal (BMI <30). RESULTS: There were no instrument-related or insertion-related
      complications. No insertion failed. Insertion time was slightly longer in the
      morbidly obese patients who had had previous umbilical surgical incisions. No
      port-site hernias have been found thus far (follow-up 6-48 months). CONCLUSION:
      This reusable cannula was found to be safe for any body weight.

PMID- 10065582
TI  - Restrictive versus malabsorptive procedures: criteria for patient selection.

PMID- 10065583
TI  - Outcome of vertical banded gastroplasty.

PMID- 10065584
TI  - Laparoscopic adjustable vertical banded gastroplasty: a new method for treatment
      of morbid obesity: preliminary experience.

PMID- 10065585
TI  - 28-month experience with the lap-band technique: results and critical points of
      the method.

PMID- 10065586
TI  - Videolaparoscopic treatment of gastric banding complications.

PMID- 10065587
TI  - Laparoscopic surgery for morbid obesity: preliminary results from SICE registry
      (Italian Society of Endoscopic and Minimally Invasive Surgery).

PMID- 10065588
TI  - Adjustable silicone gastric banding: use of the ultrasound technology in
      laparoscopic approach.

PMID- 10065589
TI  - Preliminary endoscopic technical report of a new silicone intragastric balloon in
      the treatment of morbid obesity.

PMID- 10065590
TI  - Binge eating in gastric bypass patients before surgery.
AB  - BACKGROUND: Binge eating in the obese, specifically those undergoing bariatric
      surgery, has only recently been investigated. This study is a continuation of a
      long-term effort to determine the impact of eating disorders on the outcome of
      bariatric surgery. METHODS: Self-report questionnaires (Binge Eating Scale, Beck
      Depression Inventory, Questionnaire on Weight and Eating Patterns) were completed
      by 125 patients preparing to undergo gastric bypass surgery. RESULTS: Binge
      eating was clearly a problem in this population, with 33.3% showing severe binge
      eating problems on the Binge Eating Scale. Over half of patients engaged in
      bingeing or grazing, most reporting a frequency of two or more times per week. A
      high level of depression was associated with binge eating. CONCLUSIONS: Because
      postsurgical long-term weight loss maintenance is contingent on modifying eating
      behavior, the identification and treatment of such disorders may be critical to
      successful long-term outcome in these patients.

PMID- 10065591
TI  - Patients with morbid obesity don't get life-saving bone marrow transplants.
AB  - When the patient, a registered nurse, was surgically treated for morbid obesity
      she initially lost 54.5 kg. Approximately 2 years after gastric bypass, she
      received a diagnosis of chronic myelogenous leukemia and subsequently underwent a
      successful allogenic bone marrow transplant (BMT). When her surgical history was
      taken at the transplant facility, the significant weight loss and gastric bypass
      were discussed. She was informed that at 140 kg, she would not have been eligible
      nor considered a candidate for transplant. A search of the literature and a
      survey of other facilities confirmed this view as typical. The reasons cited were
      that the chemotherapy dosage required for the morbidly obese weight level would
      cause fatal organ damage as opposed to organ-sparing dosages, which would not
      eradicate all leukemic cancer cells. An additional general view was that the
      morbidly obese could not survive the rigors of the transplant preoperative
      regimen. This patient had an uneventful recovery and remains disease-free today,
      3 years after BMT and 5 years after gastric bypass, with a sustained total weight
      loss of 73 kg.

PMID- 10065592
TI  - Success habits of long-term gastric bypass patients.
AB  - BACKGROUND: By identifying common habits of the most successful long-term gastric
      bypass patients, one is able to establish more specific guidelines for new
      patients to follow. The first postoperative year is a critical time that must be
      dedicated to changing old behavior and forming new, lifelong habits. METHODS: 100
      gastric bypass patients from 1979 to 1995 participated in a comprehensive survey.
      Surveys were completed in person, by phone, or in writing. Participants were
      asked to answer questions regarding their eating, drinking, sleeping, exercise,
      and personal habits. RESULTS: The survey revealed that specific habits are common
      in gastric bypass patients who have maintained their weight loss for many years.
      CONCLUSION: Identifying and defining the common habits of patients who are
      successful with long-term weight loss enabled specific guidelines to be
      established for new patients to implement during the initial weight loss phase,
      which will contribute to life-long success.

PMID- 10065593
TI  - Determination of platinum in rat dorsal root ganglion using ICP-MS.
AB  - This study evaluated the performance of inductively coupled plasma mass
      spectrometry for the determination of platinum (Pt) in rat dorsal root ganglion.
      The method detection limit was found to be 0.008 ng/mL of Pt, which corresponds
      to 4 pg of Pt per milligram of ganglia. The standard deviations in the tissue
      matrix were 5.7% or better and minimum matrix effect was observed. Compared to
      indium, the use of iridium or a combination of iridium and bismuth as internal
      standard(s) provided more accurate measurement. The Pt in the tissue digestate
      was stable for a minimum of 46 d at levels above 0.05 ng/mL. Flow injection
      analysis using undiluted digestates resulted in approximately 20% signal
      enhancement. Internal standard correction was necessary to obtain accurate
      results. The method was used in initial studies in which rats were dosed with
      cisplatin and has shown that Pt accumulates and persists in dorsal rat ganglion
      following treatment.

PMID- 10065594
TI  - Manganese transport by Caco-2 cells.
AB  - The uptake and transport kinetics of manganese (Mn) were investigated in the
      human intestinal Caco-2 cell line both from the absorption side (apical to
      basolateral) and from the exsorption side (basolateral to apical). With regard to
      the former, transport versus time revealed (as uptake) a biphasic pattern with an
      initial transient phase followed by steady-state conditions. Uptake versus Mn
      concentrations showed saturation-type kinetics with a 100% increase of Mn binding
      capacity when measurements were made from 0.5 to 2 h of incubation. The transport
      characteristics in steady-state conditions exhibited two components, saturable
      (Vmax = 3.70+/-0.07 nmol/cm2/h, K(m) = 32.2+/-3.4 microM) and nonsaturable (slope
      = [1.4+/-0.2] x 10(-6)cm(-2)/h) usually presumed to reflect transcellular
      (carrier mediated) and paracellular (diffusional) pathways, respectively. Mn
      fluxes were decreased by calcium and calcium antagonists, almost 100% inhibited
      at 4 degrees C, and affected by quinacrine and ouabain. The inhibition of ATP
      synthesis was apparently ineffective. From the exsorption side, the Mn fluxes,
      without a transient period, had an approx 20-fold smaller rate than in the
      absorptive direction and showed mainly a nonsaturable route (slope = [0.6+/-0.1]
      x 10(-6) cm(-2)/h). The mechanisms participating in the Mn movements through the
      monolayer are discussed and proposed to be in common, at least partly, with other
      divalent cations such as calcium, zinc, or iron.

PMID- 10065595
TI  - Testicular atrophy, zinc concentration, and angiotensin-converting enzyme
      activity in the testes of vitamin A-deficient rats.
AB  - Angiotensin-converting enzyme (ACE) as a part of the renin angiotensin system
      (RES) regulates blood pressure and fluid and electrolyte homeostasis, and the
      enzyme is considered to have a function in reproduction. Reduced enzyme
      activities have been observed in atrophied testes as a results of zinc and
      pituitary deficiencies. Vitamin A deficiency causes atrophy of testes. The
      present study was conducted on three groups of male, 3-wk-old, Wistar rats. After
      54 d of the experimental period, testicular weights of the vitamin A-deficient
      rats (A- group, allowed free access to vitamin A- deficient diet) was
      significantly lower than its pair-fed, PF (given restricted amount control diet)
      and A+ (allowed free access to control diet) groups. Zinc concentrations and both
      soluble and particulate ACE activities in the testes of vitamin A- deficient rats
      (A- group) were significantly lower than the other two groups. No significant
      differences were observed regarding zinc concentration, particulate ACE, and
      total ACE activities in the testes of PF and A+ groups. Vitamin A deficiency did
      not significantly affect the enzyme activity in the lung. From the observations
      of the present study, we speculate that testicular atrophy in vitamin A
      deficiency may have resulted from lower zinc concentration and decreased ACE
      activity in that organ.

PMID- 10065596
TI  - Long-term effects of iron:zinc interactions on growth in rats.
AB  - The influence of iron (Fe) on the bioavailability and functional status of zinc
      (Zn) was studied in young rats using metabolic balances and tissue dosages, which
      were compared to growth. Diets supplied adequate intakes of Fe (45 and 300 mg/kg
      diet) and Zn (14 and 45 mg/kg) for 2 mo. Two metabolic balance determinations
      were performed that were correlated for Zn and Fe during the first and the last
      weeks of the study. A significant effect of Fe supply, but not of Zn was
      displayed on Fe absorption; both Fe and Zn diet concentrations had a significant
      influence on Zn absorption. Fe and Zn organ contents were significantly
      correlated with the amount absorbed during the two metabolic balances. There was
      a positive correlation between liver and muscle Fe and Fe absorption, and Fe
      absorption and muscle Zn, as well as a negative one with liver Zn; a positive
      correlation was displayed between Zn absorption and Zn organ content. No
      correlation was found between Zn absorption and Fe tissue content. Growth was
      correlated with Zn, but not with Fe absorption during both balances. A positive
      correlation was displayed between growth and Zn liver content, and a negative one
      with Fe liver content. Care must be taken to give growing subjects balanced diets
      or supplementation, since the negative interactions between these trace elements
      are likely to persist as long as the diet is given.

PMID- 10065597
TI  - Serum selenium levels in healthy Slovak children and adolescents.
AB  - Blood serum selenium levels were measured in 891 healthy children and adolescents
      (aged 11-18 yr, 450 girls and 441 boys) residing in both rural and urban areas
      from eight regions of Slovakia. Subjects were divided into four age groups (11-12
      y, 13-14 y, 15-16 y, and 17-18 y). Serum selenium concentration was determined by
      the electrothermal atomic absorption spectrometric method. The mean (+/-SD) serum
      selenium concentrations were 0.750+/-0.255 micromol/L in girls and 0.773+/-0.235
      micromol/L in boys. A large proportion of the individuals (25.7% in girls, 18.1%
      in boys) exhibited serum selenium levels under 0.57 micromol/L (45 microg/L). An
      increasing trend of the serum selenium values with age has been observed in both
      boys (p < 0.01) and girls (p < 0.05). Boys had higher serum selenium levels in
      the all age groups but the differences were not statistically significant.

PMID- 10065598
TI  - Environmental factors, health-related habits, and serum selenium levels in cancer
      patients and healthy controls.
AB  - Previous studies conducted in Yugoslavia indicated that the concentration of
      selenium in soil, food items, and serum of the population is very low. The aim of
      the study was to investigate the possible relationship among environmental,
      health-related habits, nutrition, and selenium serum levels in cancer patients
      and the healthy population. The case-control study included a group of cancer
      patients and a matched group of healthy controls: 57 cancer patients and 41
      healthy controls living in Stari Grad (an urban area of Belgrade), as well as 17
      cancer patients and 13 healthy controls living in Barajevo (a rural community in
      the vicinity of Belgrade). The healthy controls were matched to cancer patients
      in sex and age; they were not blood related. The selenium serum levels were
      measured by atomic absorption spectrophotometry. Health-related habits and
      relevant dietary factors ("food frequency" method) that may influence the
      selenium serum levels were assessed by questionnaires. The differences in average
      values of selenium serum levels between the cancer patients and healthy controls
      were not significantly different, but both were below the lowest recorded in
      referential studies. A significant difference between the values obtained from
      urban and rural subgroups was noted. The most important factors that influenced
      the level of selenium included the residence place in the region with selenium
      deficiency (Barajevo), age, associated chronic diseases, and some dietary factors
      potentially related to the intake of selenium. The results obtained in this
      investigation pointed out that use of selenium supplementation in this area
      should be seriously considered.

PMID- 10065599
TI  - Potential carcinogenicity of some transition metal ions.
AB  - Potential carcinogenicity of some transition metal ions was tested using a direct
      current polarography method. The measurements were based on the reduction of
      tested compounds in an anhydrous solution using alpha-lipoic acid as the
      detection compound. The potential carcinogenicity was expressed in terms of the
      parameter tg alpha, which is known to directly correlate with the carcinogenicity
      of tested compounds. For the metal ions tested, tg alpha was found to decrease in
      the following sequence: Fe(III) > Pb(II) > V(IV) > Fe(II) > Mn(II) > Cu(II). Zero
      values of tg alpha were found for Cd(II) and Mn(III).

PMID- 10065600
TI  - Plasma micronutrient concentrations in infants undergoing therapy for
      phenylketonuria.
AB  - Twenty-seven infants with classical phenylketonuria were evaluated longitudinally
      for 6 mo while ingesting Phenex-1 Amino Acid Modified Medical Food With Iron as
      their primary protein source. Intake of selected nutrients and biochemical
      indices of trace and ultratrace mineral status and plasma retinol and alpha
      tocopherol concentrations were evaluated. The means of iron status indices
      (complete blood count, plasma ferritin, iron, transferrin saturation, total iron
      binding capacity) and the plasma concentrations of trace and ultratrace minerals
      (copper, manganese, molybdenum, selenium, zinc) and plasma retinol and alpha
      tocopherol were in the reference ranges. Vitamin A intakes (r = 0.49, p < 0.05)
      and plasma retinol-binding protein concentrations (r = 0.42, p < 0.05) were
      positively correlated with plasma retinol concentrations at 3 mo of study. At 6
      mo, concentrations of plasma transthyretin (r = 0.72, p < 0.01) and retinol
      binding protein (r = 0.48, p < 0.05) were positively correlated with plasma
      retinol concentrations. At 6 mo, concentrations of plasma transthyretin (r =
      0.52, p < 0.05) were positively correlated with retinol-binding protein
      concentrations. Phenex-1 supports normal mean iron status indices and mean
      concentrations of trace and ultratrace minerals, retinol, and alpha-tocopherol
      when fed in adequate amounts.

PMID- 10065601
TI  - Alterations in serum and brain trace element levels after antidepressant
      treatment: part I. Zinc.
AB  - We have studied the effect of chronic treatment with imipramine, citalopram and
      electroconvulsive shock (ECS) on serum and brain zinc levels in rats. Chronic
      treatment with citalopram (but not with imipramine or ECS) significantly (approx
      20%) increased the serum zinc level. Chronic treatment with both drugs slightly
      (by approx 10%) increase the zinc level in the hippocampus and slightly decreased
      it in the cortex, cerebellum and basal forebrain. Calculation of the ratio
      hippocampus/brain region within each group demonstrated a significantly (approx
      20%) higher value after treatment with either imipramine or citalopram. Moreover,
      chronic ECS induced a significant increase (by 30%) in the zinc level in the
      hippocampus and also a slight increase (by 11-15%) in the other brain regions.
      Thus, these different antidepressant therapies induced an elevation of the
      hippocampal zinc concentration, which indicates a significant role of zinc in the
      mechanism of antidepressant therapy.

PMID- 10065602
TI  - Pityriasis rubra pilaris.

PMID- 10065603
TI  - Is psoriasis a neuroimmunologic disease?

PMID- 10065604
TI  - The role of salicylic acid in the treatment of psoriasis.

PMID- 10065605
TI  - Dermatology in the new millennium.

PMID- 10065606
TI  - Nehushtan: Iberia, Humpty Dumpty, and modern medicine.

PMID- 10065607
TI  - Childhood pemphigus.
AB  - BACKGROUND: Five children with pemphigus are reported: three with pemphigus
      vulgaris, one with pemphigus vegetans, and one with pemphigus foliaceus. Only one
      case of juvenile pemphigus vegetans has been published in the literature.
      MATERIALS AND METHODS: All three patients with pemphigus vulgaris were treated
      with oral corticosteroid; in two cases, azathioprine was added for steroid
      sparing effect. The patient with pemphigus vegetans had a clinical presentation
      resembling pemphigus vulgaris, but the lesions in the perianal area healed as
      hypertrophic granulation tissue. He was treated with oral corticosteroid,
      azathioprine, and intralesional corticosteroid. The patient with pemphigus
      foliaceus presented with exfoliative dermatitis, and was treated with oral
      corticosteroid; methotrexate was added later for steroid-sparing purposes
      RESULTS: The patients were followed up for 1-4 years; the prognosis of childhood
      pemphigus is good. CONCLUSIONS: Long-term follow-up is needed to detect flaring
      of the disease and the side-effects of immunosuppressive drugs.

PMID- 10065608
TI  - Pemphigus and pemphigoid-like effects of nifedipine on in vitro cultured normal
      human skin explants.
AB  - BACKGROUND: A variety of drugs have been implicated in the onset and exacerbation
      of pemphigus and bullous pemphigoid. The demonstration of biochemical
      acantholysis in skin explants to various drugs in the absence of autoantibodies,
      in which the tested drugs evoke a biochemical reaction that leads to desmosomal
      function loss, may be a valuable adjunct to patient management by confirming the
      suspicion of drug-related pemphigus or bullous pemphigoid. OBJECTIVE: To
      determine whether a skin explant model might serve as a possible in vitro
      correlate of drug-induced pemphigus and pemphigoid-like effects related to the
      calcium channel blocker nifedipine. METHODS: Normal human breast skin obtained
      from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured
      with nifedipine at final concentrations of 2, 4, and 8 mM. The drug effect on
      skin explants evidenced by morphologic changes was evaluated by microscopy by
      three observers. RESULTS: Five out of seven explants cultured with nifedipine at
      concentrations ranging from 2 to 8 mM exhibited obvious morphologic changes of
      two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or
      pemphigoid-type) splittings. Two explants showed no acantholysis and no
      subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG)
      showed no changes. Skin control samples cultured in medium supplemented with 10%
      PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign
      of cell-cell dyshesion or dermo-epidermal detachment. CONCLUSIONS: A type of skin
      susceptibility to nifedipine may be genetically determined, with some nifedipine
      treated patients developing an acantholytic reaction and others a subepidermal
      bullous eruption.

PMID- 10065609
TI  - Sensitivity of indirect immunofluorescence and immunoblotting for the detection
      of intercellular antibodies in endemic pemphigus foliaceus (fogo selvagem).
AB  - BACKGROUND: Two assays are available to detect anti-skin antibodies in patients
      with fogo selvagem (FS): indirect immunofluorescence (IIF) and immunoblotting
      (IB). This study was conducted to compare the sensitivity of these assays in
      detecting FS antibodies. DESIGN: Eighty-nine serum samples of 48 patients with FS
      and control serum from 15 normal individuals were tested concurrently for the
      presence of FS antibodies by IIF and IB. IIF studies were conducted using four
      different substrates: human skin, monkey and guinea pig esophagus, and bovine
      tongue. RESULTS: FS antibodies were detected much more commonly by IIF than by
      IB, i.e. in 71% vs. 28% of serum samples respectively. By IIF, the antibodies
      reacted most strongly against human skin. CONCLUSIONS: IIF is a more sensitive
      assay than IB for detecting antibodies associated with FS. The sensitivity of the
      test is maximized by using human skin as a substrate.

PMID- 10065610
TI  - Class II major histocompatibility complex typing across the ethnic barrier in
      pemphigoid gestationis. A study in Mexicans.
AB  - BACKGROUND: Pemphigoid gestationis (PG), also called herpes gestationis, is a
      rare autoimmune disease of pregnancy or puerperium (estimated 1 out of 50,000
      pregnancies among Caucasians). A previous series has demonstrated an association
      of PG with human leukocyte antigen (HLA)-DR3 or HLA-DR4 haplotypes. While these
      haplotypes are most commonly found in individuals of European ancestry, they have
      also been found in African-American patients affected with PG. PG has rarely been
      reported in other ethnic groups, and the HLA association in non-Europeans has not
      been examined. METHODS: We have characterized eight patients of Mexican ancestry
      who have PG by clinical, histologic, and immunofluorescence criteria. Class I and
      class II major histocompatibility complex (MHC) antigens were studied by standard
      microlymphocytotoxicity assays. Class II MHC antigens were further studied by
      polymerase chain reaction (PCR) amplification of HLA-DRB1, DQA, and DQB genes and
      allele-specific oligonucleotide hybridization. For comparison purposes, we used
      results obtained from a group of 100 ethnically matched healthy individuals.
      RESULTS: We found that all eight patients had the HLA-DR3/DR4 phenotype; all HLA
      DR3 haplotypes were HLA-DRB1*0301, DQA1*0501, and DQB1*0201, whereas half of the
      HLA-DR4 haplotypes were from the DRB1*0401 subtype and the other half were DRB1
      *0407. CONCLUSIONS: These results suggest that, in Mexicans, the genetic
      susceptibility for the development of PG is strongly influenced by the genetic
      admixture of Caucasian origin, and the role of class II MHC antigens in the
      pathophysiology of this disease is confirmed.

PMID- 10065611
TI  - Erythema multiforme following the exacerbation of hepatitis B virus infection.

PMID- 10065612
TI  - Lichenoid secondary syphilis.

PMID- 10065613
TI  - Human gnathostomiasis (nodular migratory eosonophilic panniculitis).

PMID- 10065614
TI  - Electron microscopy comparison of CO2 laser flash scanning and pulse technology
      one year after skin resurfacing.
AB  - BACKGROUND: The recent adaptation of laser technology in plastic and dermatologic
      surgery has provided a means to reduce efficiently the irregularities of the
      surface of the skin. Previous studies have analyzed the short- and medium-term
      clinical and histologic results of two laser systems: the Sharplan 40C SilkTouch
      and the 5000C Coherent Ultrapulse with Computer Pattern Generator (CPG). This
      paper contains the long-term ultrastructural findings observed with the aid of
      transmission electron microscopy (TEM). MATERIALS AND METHODS: Twenty skin biopsy
      specimens were taken from ten Caucasion patients, between 54 and 72 years of age,
      who had undergone facial skin resurfacing with a CO2 laser 1 year previously. The
      treated areas of the face were divided into two equal parts. One half of the face
      was treated with the Sharplan SilkTouch laser and the other half with the
      Coherent Ultrapulse laser. Using TEM, the cell composition of the epidermis was
      studied ultrastructurally, as were the dermal-epidermal junction (DEJ) and the
      different fibers and cells in the superficial and middle dermis. RESULTS: On the
      side treated by the Sharplan laser, little melanin was observed, the DEJ was
      thicker, and there were abundant collagen fibers well compacted in the dermis.
      Also present was abundant elastin fiber with scarce interstitial spaces. On the
      side treated by the Coherent, the melanin was abundant and the DEJ was well
      structured. There were fibroblasts with lax chromatin in the dermis and collagen
      fibers in the papillary dermis oriented in a vertical and horizontal manner in
      relation to the epidermis. There was little elastin. The interstitial spaces were
      abundant. CONCLUSIONS: The Sharplan laser system seems to provoke a significantly
      more intense tissue response, with abundant dermal collagen and elastic fibers.
      This indicates that the Sharplan 40C SilkTouch might produce longer lasting
      clinical effects.

PMID- 10065615
TI  - Effects of gemfibrozil on in vitro cultured normal human skin explants.
AB  - BACKGROUND: Several lipid-lowering agents, when given topically, show a profound
      effect on skin morphology. Because of low bioavailability of these drugs for
      keratinocytes, the incidence is extremely low clinically. The most appropriate
      way to study the effect of hypolipidemic drugs on keratinocytes is by artificial
      exposure of the skin to high drug concentrations. OBJECTIVE: To study the effects
      of gemfibrozil on the morphology of in vitro cultured normal human skin explants.
      As gemfibrozil induces barrier disruption by inhibiting epidermal sterologenesis,
      essential for a competent permeability barrier, it is interesting to investigate
      the morphologic changes associated with this phenomenon. Studying the epidermal
      changes induced by lipid-lowering agents is important, not only because it might
      lead to a better understanding of the effects of these drugs on keratinocytes,
      but as it might also unlock the door to a wider knowledge of the pathomechanism
      of disorders of cornification. METHODS: Normal human skin from patients
      undergoing mastectomy was cultured in the presence of 2, 5, and 10 mM of
      gemfibrozil for 4 days The morphologic changes were evaluated by three blinded
      observers. Their reports were matched and collated. RESULTS: The cultured skin in
      the presence of gemfibrozil showed cell crowding of keratinocytes in the lower
      part of the epidermis, indicating epidermal hyperplasia and increased
      proliferation. Intercellular edema with the formation of small cavities in the
      epidermis, intracellular edema, and vacuolar alteration of keratinocytes in the
      upper portion of the epidermis were also observed. The intensity of these changes
      tended to parallel the gemfibrozil concentration. Some dermo-epidermal
      detachments did not correlate with the gemfibrozil concentration, but rather with
      tissue characteristics peculiar to each explant. CONCLUSIONS: The morphologic
      changes caused by gemfibrozil to normal human skin were not characteristic of
      psoriasis, and included intracellular and intercellular edema in the upper
      portion of the epidermis and cell crowding, indicating epidermal hyperplasia in
      the lower portion of the epidermis. The present experimental study gives further
      support to the hypothesis that hypolipidemic drugs cause an initial break in the
      barrier function of the epidermis, followed by a physiologic epidermal response,
      aimed at barrier restoration. This rather nonspecific stimulus to epidermal
      proliferation may trigger psoriasis in predisposed patients.

PMID- 10065616
TI  - Clofazimine therapy for lepromatous leprosy: a historical perspective.

PMID- 10065617
TI  - Disseminate and recurrent infundibulofolliculitis: response to psoralen plus UVA
      therapy.

PMID- 10065618
TI  - Thalidomide as an inhibitor of tumor necrosis factor-alpha production: a word of
      caution.

PMID- 10065619
TI  - Macrophage-restricted molecules: role in differentiation and activation.
AB  - Membrane antigens serve as excellent markers of murine macrophage (MO)
      differentiation in vivo and in vitro, and have yielded insights into novel MO
      functions in innate and acquired immunity. We review briefly the use of a range
      of monoclonal antibodies against MO which show restricted expression: F4/80,
      macrosialin and sialoadhesin. Differential display PCR strategies have made it
      possible to identify a novel MO-restricted membrane molecule, a murine MO C-type
      lectin (mMCL). The isolation of functionally active ab against known receptors
      such as the scavenger receptor, Class A (SR-A) has provided a key reagent to
      characterise the role of this molecule in adhesion, endocytosis, phagocytosis and
      in the regulation of cellular immunity. Studies in SR-A ko mice challenged with
      BCG and LPS show that the SR-A molecule helps to limit excessive production of
      cytokines such as TNFalpha by MO that have been activated by infection, and thus
      protects the host against septic shock.

PMID- 10065620
TI  - Potential role of the mannose receptor in antigen transport.
AB  - Potential endogenous ligands for the cysteine rich domain of the murine mannose
      receptor (MR) have been detected in marginal zone metallophilic macrophages in
      spleen and subcapsular sinus macrophages in lymph nodes of naive mice by
      immunohistochemistry using a Fc chimeric protein. Additional labelling was
      observed in follicular dendritic cells and migratory dendritic cells in immunised
      animals. Based on this labelling pattern and the identification of a soluble form
      of the MR in macrophage-conditioned media and mouse serum, we propose a novel
      role for this receptor in antigen transport.

PMID- 10065621
TI  - Class A scavenger receptors and the phagocytosis of apoptotic cells.
AB  - Apoptotic cells are rarely seen in situ because of rapid clearance by phagocytes.
      A number of receptors have been implicated in the recognition and ingestion of
      dying cells. Class A scavenger receptors (SRs) are multi-domained membrane
      glycoproteins that can endocytose modified lipoproteins and bind a wide range of
      ligands. There is growing evidence that they contribute to several biological
      processes. We present data that suggest class A SRs are involved in the
      phagocytosis of apoptotic cells.

PMID- 10065622
TI  - T-cell turnover in vivo and the role of cytokines.
AB  - In addition to responding to specific antigen, CD8+ T-cells with a memory
      (CD44hi) phenotype undergo bystander proliferation when exposed to certain
      cytokines, notably type I interferons (IFN I), in vivo; such proliferation does
      not require T-cell receptor ligation. Since IFN I is unable to induce
      proliferation of purified CD44hi CD8+ cells in vitro, stimulation of these cells
      in vivo may reflect IFN I-dependent release of other cytokines. Evidence is
      presented that IFN I induces macrophages to synthesize IL-15 mRNA and that, at
      the protein level, IL-15 causes selective stimulation of CD44hi CD8+ (but not
      CD4+) cells, both in vitro and in vivo. This finding raises the possibility that
      synthesis of IL-15 during infection may induce bystander proliferation of memory
      phenotype CD8+ cells.

PMID- 10065623
TI  - IgE and tumor necrosis factor in malaria infection.
AB  - IgE, the immunoglobulin instrumental in atopic diseases is also elevated in many
      infections. This paper reports on the occurrence and possible pathogenic role of
      IgE in human Plasmodium falciparum malaria, one of the most widely spread and
      severe infectious diseases world wide. Plasmodial infections induce IgE elevation
      in the blood of the majority of people living in malaria endemic areas and up to
      5% of this IgE constitutes anti-malaria antibodies. Production of IgE is
      controlled by T cells and elevated IgE concentrations in the blood of malaria
      patients are the result of an increased ratio of T-helper 2 (Th2) over T-helper 1
      (Th1) cells. The underlying Th1 to Th2 switch is controlled by a variety of
      environmental and genetic factors. The importance of the latter is demonstrated
      by the IgE levels occurring in monozygotic or dizygotic twins originating from
      malarious areas of Africa. While these levels were indistinguishable within
      monozygotic twin pairs, they were different within the dizygotic pairs.
      Comparison of the levels of total IgE or IgE anti-malaria antibodies in patients
      with uncomplicated malaria with those in patients with the severe form of the
      disease (cerebral malaria or severe malaria without cerebral involvement)
      indicate that these levels are significantly higher in the cases with severe
      disease. This is the reverse with IgG and suggests that IgE plays a role in
      malaria pathogenesis. An important pathogenic mediator causing malaria fever and
      tissue lesions is tumor necrosis factor (TNF), generally believed to be induced
      by toxins released from the parasite. However, sera from malaria patients can
      also cause TNF release from monocytes in a reaction dependent on the presence of
      IgE containing immune complexes or aggregates. This results in induction and
      cross-linking of Fcepsilon receptor II (CD23) and by binding to and activating
      these cells, IgE will contribute to a local over-production of TNF in capillaries
      and post-capillary venules where P. falciparum parasites or their products
      accumulate in the severe forms of this disease.

PMID- 10065624
TI  - Chemokine receptors and their role in leukocyte activation.
AB  - Chemokines were originally isolated based on their abilities to selectively
      attract and recruit leukocyte populations. Over the last few years there has been
      an explosion in the number of new chemokines identified, and as a result many
      receptors previously considered to be orphans have now been paired up with their
      ligands. Here we review some of the latest results in this area, illustrating
      with data from our laboratory. The central question from a drug discovery
      perspective, is to show whether inhibiting chemokine receptors leads to a change
      in disease status. Although we are still a long way from having candidate
      molecules to take into the clinic, a flavour of what may be possible can be
      inferred from mutant chemokines with antagonistic properties. We discuss recent
      data using two of these proteins, Met-RANTES which has anti-inflammatory
      properties, and AOP-RANTES which has been shown to prevent infection of
      macrophages and T-cells by M-tropic HIV strains.

PMID- 10065625
TI  - Checkpoints for regulation of development and IFN-gamma production by Th1 cells
      in TCR-transgenic models.

PMID- 10065626
TI  - Cotton rats (Sigmodon hispidus): an animal model to study the pathogenesis of
      measles virus infection.
AB  - Measles is still the most lethal infectious disease of infants worldwide. In
      spite of research efforts, two major problems associated with measles virus (MV)
      infection have not been resolved. One is the marked immune suppression leading to
      subsequent (often lethal) opportunistic infections and the second is waning of
      maternal antibodies which do not protect against wild type virus infection any
      longer, but impair vaccination. Monkeys are an animal model in which MV infection
      most closely resembles the human disease. The use of monkeys is restricted by
      ethical and financial reasons and their availability. A cost-effective
      alternative is the cotton rat (Sigmodon hispidus). Cotton rats are the only
      rodents which replicate measles virus in lung tissue after intranasal infection.
      Our research has shown that cotton rats are a valid model to study MV induced
      immune suppression and to test vaccine candidates. It is also useful for
      comparing various wild type measles virus strains as well as recombinant measles
      viruses.

PMID- 10065627
TI  - Interleukin-12 administration in retroviral infection of mice increases the
      potential to produce functional dendritic cells from bone marrow stem cells.
AB  - Rauscher leukaemia virus (RLV) infection in mice causes production of lymph node
      and skin dendritic cells (DC) that fail to stimulate a primary mixed leukocyte
      reaction (MLR). Treatment of mice with IL-12 around the time of infection results
      in DC with normal stimulatory function (N.J. Williams, J.J. Harvey, I. Duncan,
      R.F.G. Booth, S.C. Knight, Cell Immunol. 183 (1988) 121-130). Here we derived DC
      from mouse bone marrow by culture with granulocyte macrophage colony-stimulating
      factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha) for 10-12 days; DC
      were generated from bone marrow cells taken from normal mice, from mice injected
      15 days earlier with RLV or from those receiving RLV plus five daily doses of 100
      ng of IL-12 starting 2 days before infection. Infection of the DC with RLV was
      assessed from nested PCR with doubling dilutions of DNA and the capacity of DC to
      stimulate a MLR was tested. DC derived from bone marrow of IL-12 treated animals
      showed at least twice the level of infection with RLV as those from non-treated
      animals although infection never exceeded 20% of the cells. DC derived from bone
      marrow of mice given RLV caused negligible stimulation of the MLR but those from
      mice additionally treated with IL-12 functioned normally. Thus, treatment of mice
      with IL-12 promoted the potential of stem cells taken 12 days after the last IL
      12 injection to develop into functional DC despite increased infection with
      virus. Treatment of mice with IL-12 may have a long term effect on the potential
      growth of DC from stem cells which may contribute to the potency of this cytokine
      in promoting cell mediated immune responses.

PMID- 10065628
TI  - Vaccinia virus immune evasion.
AB  - Vaccinia virus expresses many virulence factors that are non-essential for virus
      replication in cell culture but are important in vivo. In this paper three
      mechanisms are described that are used by vaccinia virus to evade the host immune
      response to infection. One of these is the release of a soluble protein that
      binds CC chemokines and that is unrelated to cellular chemokine receptors. The
      other two mechanisms are displayed by virus particles that are released from
      infected cells. This form of vaccinia virus is called extracellular enveloped
      virus (EEV) and is resistant to neutralisation by antibody and to destruction by
      complement. Resistance to complement is mediated by the acquisition of host
      complement control proteins, particularly CD55, during virus release from
      infected cells.

PMID- 10065629
TI  - The role of the viral glycoprotein in HIV-1 persistence.
AB  - The study of the immunological defects which arise from HIV infection has led to
      a deeper understanding both of the normal immune system and of the mechanisms by
      which it is damaged in disease. The interactions between viral and host factors
      during the early stages of HIV infection leads to a post-seroconversion steady
      state or 'set point' of viral RNA load, which has been shown to be a prognostic
      marker for subsequent progression rates, further underlining the important role
      of early immunological responses in the disease process. The changing immune
      response during the course of infection, together with the changing patterns of
      antigenicity and tropism leads to a complex series of evolutionary interactions
      which can be monitored as a series of changes in the properties of the virus over
      time. Furthermore, significant differences may be seen between the antigenicity
      of viruses adapted to grow in tissue culture and viruses cultured only briefly in
      primary cells, and also between the antigenicity of monomeric and oligomeric
      subunit immunogens. The immunodominant, highly polymorphic and rapidly changing
      envelope glycoproteins of HIV remains the single biggest target for the design of
      successful candidate vaccines. The recent crystallisation of one HIV envelope,
      the proven existence of functionally conserved neutralisation targets and our
      increasing knowledge of the behaviour of the envelope glycoprotein in vivo offers
      the possibility that the next generation of vaccine candidates will have a far
      higher chance of success than has currently been achieved.

PMID- 10065630
TI  - Genetic regulation of macrophage activation: understanding the function of Nramp1
      (=Ity/Lsh/Bcg).
AB  - The Nramp1 gene was originally described as Ity/Lsh/Bcg, a single gene
      controlling resistance and susceptibility of inbred mice to a range of
      intramacrophage pathogens. Functional studies demonstrated that Ity/Lsh/Bcg had
      multiple pleiotropic effects on macrophage activation pathways, broadening
      interest in the gene to include its candidacy as an autoimmune disease
      susceptibility gene. In 1993 the gene was positionally cloned and found to encode
      a polytopic integral membrane protein of unknown function. Subsequent studies
      have localized the protein to late endosomal and lysosomal compartments, and
      demonstrated that it functions as an iron transporter. Precisely how this
      function influences macrophage activation pathways is still under investigation,
      but is likely to include direct effects on pathogen survival in the
      endosomal/lysosomal compartment as well as influences on intracellular signalling
      pathways and in regulating mRNA stability. Several studies now provide evidence
      for a role for NRAMP1 in determining human susceptibility to autoimmune
      (rheumatoid arthritis. juvenile rheumatoid arthritis, diabetes, Crohn's disease)
      and infectious (tuberculosis, leprosy) diseases. Amongst these. data are
      accumulating to support the hypothesis that a functional Z-DNA forming repeat
      polymorphism in the promoter region of human NRAMP1 contributes directly to
      disease susceptibility. Four alleles have been observed, alleles 1 and 4 are rare
      (gene frequencies approximately equal to 0.001), alleles 2 and 3 occur at gene
      frequencies approximately 0.25 and approximately 0.75, respectively. In the
      absence of exogenous stimuli, alleles 1, 2 and 4 are poor promoters of gene
      expression in a luciferase reporter gene system; allele 3 drives high expression.
      Allele 3 shows allelic association with autoimmune disease susceptibility, allele
      2 with infectious disease susceptibility. Hence, balancing selection is likely to
      be maintaining these two alleles in human populations. Although the association
      of NRAMP1 with autoimmune disease susceptibility may be related to any one of the
      multiple pleiotropic effects associated with macrophage activation, the function
      of NRAMP1 as an iron transporter now prompts more interesting speculation that
      regulation of iron transport may contribute directly to the disease phenotype in
      arthritic disease. Patients suffering from rheumatoid arthritis show increased
      deposition of iron in the synovial membrane, which may contribute to free radical
      generation and local inflammation. Further analysis of NRAMP1 function will
      continue to be of importance in understanding the molecular basis to autoimmune
      and infectious disease susceptibility.

PMID- 10065631
TI  - Impact of intracellular location of and antigen display by intracellular
      bacteria: implications for vaccine development.
AB  - Intracellular bacteria are primarily controlled by T-lymphocytes. The
      'phagosomal' bacteria such as Salmonella enterica and Mycobacterium bovis BCG
      remain in the phagosome. These microbes primarily stimulate CD4 T-cells via
      antigen presentation through MHC class II molecules. In contrast, Listeria
      monocytogenes egresses from the phagosome into the cytoplasm by virtue of
      listeriolysin. This 'cytoplasmic' pathogen is controlled by CD8 T-cells through
      MHC class I antigen presentation. Some bacterial pathogens such as Mycobacterium
      tuberculosis presumably remain in the phagosome but apparently 'perforate' the
      phagosomal membrane and thus stimulate both CD4 and CD8 T-cells. We have
      constructed S. enterica and M. bovis BCG vaccine carriers which secrete
      listeriolysin. Such constructs are capable of introducing antigens into the MHC
      class II and MHC class I pathway, resulting in stimulation of both CD4 and CD8 T
      cells. Moreover, we constructed S. enterica vaccines which display one and the
      same listerial antigen in secreted and somatic form. Secreted antigen display was
      found to be superior to somatic antigen display. Hence, we consider antigen
      secretion a major prerequisite of an effective vaccine against intracellular
      bacteria.

PMID- 10065632
TI  - Uptake and processing of glycosylated mycolates for presentation to CD1b
      restricted T cells.
AB  - Antigen presenting cells (APCs) expressing CD1b mediate the specific T cell
      recognition of mycobacterial lipid antigens. These lipid antigens require
      internalization by APCs prior to presentation, but the detailed mechanisms of
      uptake and intracellular processing are not known. Here we have examined several
      steps in the presentation of two related classes of CD1b-presented antigens, free
      and glycosylated mycolates. T cell recognition of glucose monomycolate (GMM) was
      blocked by agents that fix APC membranes or neutralize the pH of endosomes,
      indicating a requirement for GMM uptake into an acidic compartment prior to
      recognition. Different T cell lines responded to free mycolate or GMM without
      crossreactivity, yet both antigens were taken up by APCs at the same rate. This
      demonstrated that differential recognition of these antigens resulted from T cell
      specificity for their hydrophilic caps and that APCs were unable to interconvert
      these antigens by enzymatic or chemical deglycosylation or glycosylation. APCs
      were also unable to cleave mycobacterial trehalose dimycolate (TDM) at its most
      chemically labile linkages to yield antigenic free mycolates or GMM. Our results
      indicate that these mycolate-containing antigens are resistant to chemical or
      enzymatic cleavage by APCs, suggesting that molecular trimming is not a universal
      feature of lipid antigen processing.

PMID- 10065633
TI  - T lymphocyte dynamics during Listeria monocytogenes infection.
AB  - Infection of mice with Listeria monocytogenes results in a robust T lymphocyte
      response that clears the pathogen and provides long term immunity from
      reinfection. The number of splenic CD4+ and CD8+ T cells and natural killer cells
      increases during primary and recall infection with L. monocytogenes, however the
      proportional increase is greatest for CD8+ T cells. The proportion of CD8 T cells
      expressing low levels of CD62L, a sign of activation, was increased among immune
      splenocytes, suggesting a substantial expansion of L. monocytogenes specific CTL.
      Analysis of CTL specific for the immunodominant LLO 91-99 epitope showed that
      essentially all were CD62Llo during the primary response, but that many
      upregulated expression of CD62L during the memory phase. Interestingly, the
      antigen specificity of nearly all additional CD62Llo CTL detected in spleens
      during recall L. monocytogenes infection can be accounted for with MHC class I
      tetramers complexed with four different epitopes. These studies demonstrate the
      complex T lymphocyte dynamics during infection with intracellular pathogens.

PMID- 10065634
TI  - Immune effector mechanism in parasitic infections.
AB  - In this article is a summary of our recent findings on the role of nitric oxide
      (NO) as an effector mechanism against the intracellular parasite, Leishmania
      major. NO is produced in large amounts in murine macrophages following activation
      by IFNgamma synthesized by Th1 cells. NO production is inhibited by IL-4, a
      product of Th2 cells. A set of stable cell surface markers has now been
      identified. ST2L and IL-18R are selectively expressed on Th2 and Th1 cells
      respectively. Antibody against ST2L can down-regulate Th2 cells in the highly
      susceptible BALB/c mice leading to control of otherwise fatal L. major infection.
      These results show directly the critical role of the balance between Th1 and Th2
      cells in cutaneous leishmaniasis.

PMID- 10065635
TI  - T-cell response in human leishmaniasis.
AB  - In the present communication we provide evidence for the existence of a Th1/Th2
      dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis.
      Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in
      these patients. Lymphocytes from individuals recovered from cutaneous
      leishmaniasis (CL) responded by IFN-gamma production following stimulation with
      Leishmania antigens whereas cells from patients recovered from visceral
      leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The
      cells producing these cytokines were predominantly CD4+. Furthermore, IL-10 plays
      an important role in the development of post kala azar dermal leishmaniasis
      (PKDL) from VL. The balance between the parasitic-specific T-cell response plays
      an important regulatory role in determining the outcome of Leishmania infections
      in humans.

PMID- 10065636
TI  - Common features of T cell reactivity in persistent helminth infections: lymphatic
      filariasis and schistosomiasis.
AB  - This review highlights striking similarities in the down-regulated inflammatory
      responses that are observed in chronic infectious diseases. It is clear that
      peripheral mononuclear cells show poor antigen-specific T cell proliferation in
      lymphatic filariasis as well as schistosomiasis. With respect to cytokines both
      Th1- and Th2-type products are down-regulated during chronic infection. Drug
      treatment restores responsiveness in both diseases indicating a link between
      infection and immune suppression. Interestingly, immunological responses in
      subjects carrying recent infections are characterized by strong proliferation to
      parasite antigen and IFN-gamma production. These heightened responses are
      gradually down-regulated with increased length of exposure to infection.

PMID- 10065637
TI  - Immune responses to the radiation-attenuated schistosome vaccine: what can we
      learn from knock-out mice?
AB  - The goal of an effective schistosomiasis vaccine has proved elusive but the
      protective immunity induced in mice by radiation-attenuated cercaria larvae
      provides an appropriate model from which such a vaccine might be developed. Using
      gene-disrupted mice, we have analysed the process of immune priming by attenuated
      larvae of Schistosoma mansoni and the nature of the pulmonary effector response
      directed against a challenge infection. Vaccination stimulates expansion of
      IFNgamma-producing T-helper cells in the skin-draining lymph nodes. IL-12 is
      crucial in determining the Thl direction of this initial response but the cells
      of origin and the parasite components which stimulate its production are unknown.
      In the effector response, focal aggregates comprising mainly mononuclear cells
      accumulate around challenge larvae in the lungs, a process orchestrated by
      IFNgamma. This cytokine up-regulates nitric oxide synthase activity but we were
      unable to implicate nitric oxide as a cytotoxic agent causing challenge parasite
      elimination. An alternative action for IFNgamma may be to up-regulate adhesion
      molecule expression, increasing the cohesiveness of effector foci the better to
      block parasite migration, but the adhesive interactions so far examined do not
      appear relevant. In contrast, TNF induction is essential to protection, and we
      are currently testing the hypothesis that it determines the speed of the effector
      response following arrival of challenge larvae in the lungs.

PMID- 10065638
TI  - HIV-1 DNA vaccines.
AB  - HIV-1 was among the original DNA vaccine targets and HIV DNA vaccines are now in
      human trials. Lack of strong correlates of protective immunity makes vaccine
      design difficult; however, DNA vaccines have the potential to be an ideal vaccine
      and therapeutic approach against HIV-1. DNA vaccines induce conformational
      dependent antibodies, mimic live vaccines but without the pathogenic potential,
      and can easily be made polyvalent. Genes which encode important CTL and antibody
      epitopes can be included while those that confer pathogenicity, virulence,
      antibody enhancement or represent non-conserved epitopes can be excluded. In our
      hands pre-treatment of muscles with bupivacaine or cardiotoxin did not offer any
      advantage over no muscle pre-treatment or gene gun inoculation of skin although
      gene gun immunization seem to favour a Th2 type response. As DNA vaccine
      candidates we have compared vaccines encoding native HIV MN gp160 with Rev
      independent synthetic genes encoding MNgp160 and MNgp120 using mammalian high
      expression codons. In these experiments the gene encoding secreted gp120 gave
      highest antibody neutralizing titers. High and fast antibody responses could also
      be obtained by transferring the HIV-1 MN V3 loop to the secreted HBsAg as a
      fusion gene vaccine. Thus, in the case of HIV-1 MN genes encoding secreted
      surface glycoproteins may be preferred instead of membrane bound envelopes. CTL
      responses were induced in all cases. However, in order to meet the high diversity
      of HIV and HLA types our approach is to include many CTL epitopes in a
      multivalent minigene vaccine. We found that gene gun DNA vaccination with minimal
      epitopes could induce specific CTL. Flanking sequences influenced the CTL
      response but was not needed. DNA vaccines encoding known and computer predicted
      CTL epitopes are now being developed.

PMID- 10065639
TI  - Oral vaccination with immune stimulating complexes.
AB  - There is a need for non-living adjuvant vectors which will induce a full range of
      local and systemic immune responses to orally administered purified antigens.
      Here we describe our experience with lipophilic immune stimulating complexes
      (ISCOMS) containing the saponin adjuvant Quil A. When given orally, ISCOMS
      containing the model protein antigen ovalbumin (OVA) induce a wide range of
      systemic immune responses, including Th1 and Th2 CD4 dependent activity, class I
      MHC restricted cytotoxic T-cell responses and local production of secretory IgA
      antibodies. More recent results indicate that ISCOMS may act partly by enhancing
      the uptake of protein from the gut. In addition, intraperitoneal injection of
      ISCOMS recruits and activates many components of the innate immune system.
      including neutrophils, macrophages, and dendritic cells. In parallel, there is
      increased production of nitric oxide (NO), reactive oxygen intermediates (ROI),
      interleukins (IL) 1, 6, 12, and gamma interferon (gammaIFN). Of these factors,
      only IL12 is essential for the immunogenicity of ISCOMS in vivo, as mucosal and
      systemic responses to ISCOMS are reduced in IL12KO mice, but not in IL4KO, IL6KO,
      inducible NO synthase (iNOS) KO, or gammaIFN receptor KO mice. We propose that
      ISCOMS act by targetting antigen and adjuvant to macrophages and/or dendritic
      cells. This pathway may be amenable to exploitation for vaccine development,
      especially if combined with another vector with a different mucosal adjuvant
      profile, such as cholera toxin.

PMID- 10065640
TI  - Simultaneous maxillary and mandibular distraction osteogenesis with a semiburied
      device.
AB  - Distraction osteogenesis is a technique utilizing natural healing mechanisms to
      generate new bone; it is commonly used to lengthen the hypoplastic mandible.
      Distraction of the maxilla and mandible as a unit is an obvious extension of the
      technique. We describe the application of a semiburied distractor to
      simultaneously lengthen the mandible and maxilla and level a canted occlusal
      plane in three cases. The indications for bimaxillary distraction are reviewed,
      including its advantages, disadvantages and limitations.

PMID- 10065641
TI  - Surgically-assisted orthopedic protraction of the maxilla in cleft lip and palate
      patients.
AB  - Fourteen children, aged 8 to 13 years, with unilateral or bilateral cleft lip and
      palate, were treated by an incomplete Le Fort I osteotomy without down-fracturing
      the maxilla, followed by traction of the maxilla by face mask for twelve weeks.
      Our results revealed a mean maxillary forward movement of 7.2 mm after three
      weeks of traction, followed by a retention period of nine weeks for callus
      maturation. There was an associated minor downward movement of the maxilla that
      caused a slight increase in the lower facial height, which improved the facial
      esthetics of the patients. The advantages of this method are: i) it allows for
      early skeletal advancement of the maxilla with new bone formation in the
      osteotomy line, ii) there is no need for inter-maxillary fixation of young
      patients and no need for rigid fixation of the maxilla by miniplates that can
      damage teeth buds and roots at this age, and iii) it can be used in young
      patients to improve esthetic appearance, an important factor in the psychological
      development of adolescents.

PMID- 10065642
TI  - Morphologic changes in the perioral soft tissues in patients with mandibular
      hyperplasia using a laser system for three-dimensional surface measurement.
AB  - Soft tissue changes following correction of mandibular hyperplasia were studied
      using a laser system for three-dimensional (3-D) surface measurement. Twelve
      subjects (7 men and 5 women; age 17-48 years) were included in this study.
      Bilateral sagittal split ramus osteotomies were performed in ten patients and
      intraoral vertical ramus osteotomies in two patients. Pre- and postoperative
      images, obtained with the laser system, were superimposed to determine
      distribution of changes in the perioral soft tissue. Mean volume changes were
      1032.3 mm3 in the Subnasale-UL area and 8700.9 mm3 in the LL-Menton area. Changes
      in both areas were symmetrical around the mid-sagittal plane in some patients and
      asymmetrical in others. This measurement system provided a simple method of
      determining 3-D changes in soft tissue following surgery and might be useful for
      clinical purposes.

PMID- 10065643
TI  - First results on daytime submandibular electrostimulation of suprahyoidal muscles
      to prevent night-time hypopharyngeal collapse in obstructive sleep apnea
      syndrome.
AB  - Daytime submandibular electrostimulation (dSE) of suprahyoidal muscles was
      applied to prevent sleep-associated collapse of the tongue into the
      hypopharyngeal airway. By placing the stimulatory electrodes intra- and
      extraorally, recruitment of stimulated muscle fibers at low current densities was
      improved. The significant impact of electrostimulation on suprahyoidal muscle
      force was initially demonstrated in healthy controls as compared to placebo
      treated volunteers. The morphology of suprahyoidal muscles was not affected by
      this treatment. A patient with obstructive sleep apnea syndrome initially
      presented with a respiratory disturbance index (RDI) of 13.2, an oxygen
      desaturation index of 23 and a minimal oxygen saturation of 75%. After two weeks
      of placebo treatment (TENS-stimulation), respiratory parameters remained
      unchanged. Two weeks of dSE treatment, however, improved the RDI to 3.9, the
      oxygen desaturation index from 23 to 2.8 and the minimal oxygen saturation from
      75% to 88%. 3D-sonography showed considerable hypertrophy of the stimulated
      muscles. These results indicate that dSE may prevent episodes of apnea induced by
      sleep-associated hypopharyngeal collapse of the tongue.

PMID- 10065644
TI  - Pseudogout of the temporomandibular joint. A case report.
AB  - A case of pseudogout occurring in the temporomandibular joint of a 76-year-old
      man is reported. The diagnostic work-up and its differential diagnosis is
      discussed.

PMID- 10065645
TI  - Congenital sinus of the upper lip. A case report.
AB  - A case report of a congenital midline sinus in the upper lip of a 13-year-old
      girl is presented. Theories proposed regarding the aetiology of this rare anomaly
      are discussed.

PMID- 10065646
TI  - Simultaneous or delayed placement of titanium implants in free autogenous iliac
      bone grafts. Histological analysis of the bone graft-titanium interface in 10
      consecutive patients.
AB  - The aim of the present study was to histologically analyse the bone graft
      titanium implant interface after six and twelve months of healing for a
      simultaneous approach and after six months for a delayed approach. For this
      purpose, screw-shaped c.p. titanium microimplants, 2 mm in diameter and 5 mm
      long, were placed and retrieved at different time intervals in ten consecutive
      patients with severely resorbed maxillae and treated with iliac cortico
      cancellous bone grafts and titanium implants in a two-stage procedure. The
      histomorphometrical analyses of ground sections of the specimens showed a higher
      degree of bone-implant contact and more bone filling the implant threads in the
      delayed approach microimplants. This was probably due to the partly
      revascularized grafted bone in the delayed approach being able to respond to the
      surgical trauma, resulting in interfacial bone formation. It is concluded that
      the results from the present study favour the use of a delayed approach when
      using free autogenous bone grafts and titanium implants for reconstruction of the
      severely atrophied maxilla.

PMID- 10065647
TI  - Operator agreement in the use of a descriptive index of edentulous alveolar ridge
      form.
AB  - CAWOOD & HOWELL have proposed a classification of the anatomical form of the
      residual alveolar processes of edentulous patients. The purpose of this study was
      to test observer agreement in the clinical assessment of edentulous alveolar
      ridge form using this classification. This was tested in a pilot study involving
      57 edentulous patients, and subsequently in a study of 557 edentulous patients.
      High levels of observer agreement were found when using this classification for
      upper and lower edentulous alveolar ridges, suggesting that the classification
      may be useful as a research tool.

PMID- 10065648
TI  - Retention force of magnets in endosteal implants used for facial prosthesis.
AB  - This study reports on forces generated by magnets to retain facial prostheses.
      The retention force was measured in cylindrical magnetic inserts and in telescope
      magnetic inserts. The forces between insert and secondary magnets were measured
      at different angles. The mean force in the axial direction was 1.8 N. The force
      decreased as the angle between force direction and insert-axis increased. The
      results will help clinicians to insert implants in an optimal position when using
      them to retain facial prostheses.

PMID- 10065649
TI  - Primary malignant melanoma of the upper aero-digestive tract.
AB  - Malignant mucosal melanoma represents 0.3 to 10% of all melanomas. The majority
      of these lesions arise in the oral cavity or paranasal sinuses. Very few authors
      report reliable treatment results, however all suggest a uniformly poor outcome.
      A retrospective analysis of all cases of upper aero-digestive tract melanoma
      (UADT) treated since 1982 at our centre are presented. During the 15-year period,
      nine cases of UADT melanoma were identified. Three patients had a lesion in the
      palate, two in the maxillary alveolus, two in the oropharynx, while one each had
      a lesion in paranasal sinus and lower alveolus. Mean age was 43.25 years (28-62
      years), with a male to female ratio of 1.6:1. Cervical lymphadenopathy was the
      commonest presenting symptom in seven patients. Radical surgery was carried out
      in three patients, wide excision in three and radical neck dissection in six,
      while no surgical intervention was undertaken in two patients. Median follow-up
      time was eleven months. In four patients, local recurrence occurred, while three
      developed pulmonary metastasis. One patient was lost to follow-up. We suggest
      that data from various centres be pooled together in order to carry out a meta
      analysis to address the question of optimal treatment for malignant melanoma of
      the upper aero-digestive tract.

PMID- 10065650
TI  - Cerebral radionecrosis following the treatment of parotid tumours: a case report
      and review of the literature.
AB  - Radiotherapy is an accepted part of the treatment of malignant tumours of the
      parotid gland. The use of radiotherapy in benign parotid tumours, where spillage
      of tumour cells has occurred at operation, is more controversial. Radiotherapy to
      the parotid bed is not without morbidity. Complications may arise as a result of
      radiation damage to neighbouring structures and there is also potential to induce
      malignant disease. A patient, whose postoperative radiotherapy following
      resection of a pleomorphic salivary gland adenoma was complicated by cerebral
      necrosis, is discussed. The literature pertaining to morbidity of radiotherapy
      for parotid tumours is reviewed.

PMID- 10065651
TI  - Survey of patients with oblique facial clefts in Japan.
AB  - Oblique facial clefts constitute approximately 0.20% of all facial malformation
      cases in Japan and approximately 0.22% in other countries. In the present study,
      the proportion in our institute was approximately 0.21%, which is almost equal to
      that reported by WILSON et al. The ratio of male and female patients did not
      differ significantly from that in other countries.

PMID- 10065652
TI  - Florid cemento-osseous dysplasia. Report of a case.
AB  - A case of florid cemento-osseous dysplasia in a 16-year-old Japanese boy is
      presented. The lesion was unusually large and affected all four quadrants.
      Progressive increase in the bulk of the lesion was seen.

PMID- 10065653
TI  - Cavernous haemangioma of the submandibular salivary gland.
AB  - Salivary gland haemangioma is more common in the parotid than in any other
      salivary gland. Parotid haemangioma is considered to be the most common salivary
      gland tumour in infants, but is also occasionally encountered in adults. A case
      of cavernous haemangioma affecting the submandibular salivary gland in an adult
      woman is presented. The striking histological feature is the presence of numerous
      vascular channels assuming a periductal arrangement.

PMID- 10065654
TI  - Toxic shock syndrome secondary to a dental abscess.
AB  - A 9-year-old girl presented with arthralgia and myalgia which progressed to
      developing renal failure and overwhelming septic shock. The underlying cause was
      assumed to be a periodontal abscess from an upper right deciduous canine tooth.
      The pus from the abscess grew a toxic shock syndrome toxin 1-producing
      Staphylococcus aureus. This case illustrates the importance of an oral surgical
      review of patients presenting with features of toxic shock syndrome if the source
      of the infection is not immediately obvious.

PMID- 10065655
TI  - Verruciform xanthoma and concomitant lichen planus of the oral mucosa. A report
      of three cases.
AB  - Verruciform xanthomas are benign muco-cutaneous lesions of unknown aetiology.
      They have a papillated surface and histologically they are characterised by the
      presence of foam cells in connective tissue papillae between elongated
      parakeratinised epithelial rete ridges. Three cases are reported in which oral
      mucosal verruciform xanthoma and oral mucosal lichen planus occurred
      concomitantly.

PMID- 10065656
TI  - A study of the effect of suction drainage on microvascular anastomosis.
AB  - The effect of suction drainage on the patency of microvascular anastomosis was
      evaluated in 20 rats. No anastomosed vessels were sucked into the suction drain.
      Histologic examination of the specimens showed normal healing of the endothelium
      across the anastomotic site and no evidence of thrombus formation. The results
      indicate that the suction pressure does not affect the patency of microvascular
      anastomosis.

PMID- 10065657
TI  - Microsurgical repair of Stensen's & Wharton's ducts with autogenous venous
      grafts. An experimental study on dogs.
AB  - This study presents the results of microsurgical repair of Stensen's and Warton's
      ducts in dogs. A method is presented which involves a special technique making
      use of a catheter and an adventitial cuff. The histological, clinical and
      sialographic results show the feasibility of this technique.

PMID- 10065658
TI  - Reconstruction of the floor of the mouth with a fascial radial forearm flap,
      prelaminated with full thickness pieces of buccal mucosa.

PMID- 10065659
TI  - Interventions for smoking cessation: the outcomes are determined by the questions
      asked.

PMID- 10065660
TI  - Bacterial infection and chronic obstructive pulmonary disease.

PMID- 10065661
TI  - Is respiratory controller arrhythmia an artifact or a real phenomenon?

PMID- 10065662
TI  - Higher dosage nicotine patches increase one-year smoking cessation rates: results
      from the European CEASE trial. Collaborative European Anti-Smoking Evaluation.
      European Respiratory Society.
AB  - The Collaborative European Anti-Smoking Evaluation (CEASE) was a European
      multicentre, randomized, double-blind placebo controlled smoking cessation study.
      The objectives were to determine whether higher dosage and longer duration of
      nicotine patch therapy would increase the success rate. Thirty-six chest clinics
      enrolled a total of 3,575 smokers. Subjects were allocated to one of five
      treatment arms: placebo and either standard or higher dose nicotine patches (15
      mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately
      intensive support. The 12 month sustained success rates were: 25 mg patch for 22
      weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22
      weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0)
      9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus
      placebo, p<0.001, Chi-squared test). There was no significant difference in
      success rate between the two active treatment durations. Of the first week
      abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first
      week smokers, 2.7% of 1,877 subjects (p< 0.001). In summary, a higher than
      standard dose of nicotine patch was associated with an increase in the long-term
      success in smoking cessation but continuation of treatment beyond 8-12 weeks did
      not increase the success rates.

PMID- 10065663
TI  - Decline in FEV1 related to smoking status in individuals with severe alpha1
      antitrypsin deficiency (PiZZ).
AB  - Severe alpha1-antitrypsin (AAT) deficiency predisposes to emphysema development.
      Highly variable rates of decline in lung function are reported in PiZZ
      individuals. The annual decline in forced expiratory volume in one second (FEV1;
      delta FEV1) was analysed in relation to smoking status in a cohort of 608 adult
      PiZZ individuals included in the Swedish national AAT deficiency register. Delta
      FEV1 was analysed in 211 never-smokers, in 351 exsmokers, and in 46 current
      smokers after performing at least two spirometries during a follow-up time of 1
      yr or longer (median 5.5 yrs, range 1-31). The adjusted mean delta FEV1 in never
      smokers was 47 mL x yr(-1) (95% confidence interval (CI) 41-53 mL x yr(-1)), 41
      mL x yr(-1) (95% CI 36-48 mL x yr(-1)) in exsmokers, and 70 mL x yr(-1) (95% CI
      58-82 mL x yr(-1)) in current smokers. A dose-response relationship was found
      between cigarette consumption and delta FEV1 in current smokers and exsmokers. In
      never-smokers, a greater delta FEV1 was found after 50 yrs of age than before. No
      sex differences were found in delta FEV1. In conclusion, among PiZZ individuals,
      the change in forced expiratory volume in one second is essentially the same in
      never-smokers and exsmokers. Smoking is associated with a dose-dependent increase
      in the change in forced expiratory volume in one second.

PMID- 10065664
TI  - Expiratory and inspiratory chest computed tomography and pulmonary function tests
      in cigarette smokers.
AB  - This study evaluated small airway dysfunction and emphysematous destruction of
      lung parenchyma in cigarette smokers, using chest expiratory high-resolution
      computed tomography (HRCT) and pulmonary function tests (PFT). The degree of
      emphysematous destruction was classified by visual scoring (VS) and the average
      HRCT number at full expiration/full inspiration (E/I ratio) calculated in 63 male
      smokers and 10 male nonsmokers (group A). The Brinkman smoking index (BI),
      defined as cigarettes x day(-1) x yrs, was estimated. Sixty-three smokers were
      divided into three groups by PFT: group B1 (n=7), with normal PFT; group B2
      (n=21), with diffusing capacity of the lung for carbon monoxide (DL,CO) > or =
      80% predicted, forced expiratory volume in one second (FEV1) < 80% pred and/or
      residual volume (RV) > 120% pred; and group B3 (n=35), with DL,CO < 80% pred,
      FEV1 < 80% pred and/or RV > 120% pred. Heavy smokers (BI > or = 600) (n=48)
      showed a significant increase in emphysema by both VS and E/I. E/I was
      significantly elevated in both group B2 (mean+/-SD 0.95+/-0.05) and B3 (0.96+/
      0.06) compared with group B1 (0.89+/-0.03). VS could not differentiate group B2
      (3.9+/-5.0) from B1 (1.1+/-1.6). These findings suggest that the
      expiration/inspiration ratio reflects hyperinflation and airway obstruction,
      regardless of the functional characteristics of emphysema, in cigarette smokers.

PMID- 10065665
TI  - Short-term associations between outdoor air pollution and visits to accident and
      emergency departments in London for respiratory complaints.
AB  - Many epidemiological studies have shown positive short-term associations between
      health and current levels of outdoor air pollution. The aim of this study was to
      investigate the association between air pollution and the number of visits to
      accident and emergency (A&E) departments in London for respiratory complaints.
      A&E visits include the less severe cases of acute respiratory disease and are
      unrestricted by bed availability. Daily counts of visits to 12 London A&E
      departments for asthma, other respiratory complaints, and both combined for a
      number of age groups were constructed from manual registers of visits for the
      period 1992-1994. A Poisson regression allowing for seasonal patterns,
      meteorological conditions and influenza epidemics was used to assess the
      associations between the number of visits and six pollutants: nitrogen dioxide,
      ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke
      (BS) and particles with a median aerodynamic diameter of <10 microm (PM10). After
      making an allowance for the multiplicity of tests, there remained strong
      associations between visits for all respiratory complaints and increases in SO2:
      a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits
      for a 18 microg x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI
      0.8-5.2) increase for a 31 microg x m(-3) increase in PM10. There were also
      significant associations between visits for asthma and SO2, NO2 and PM10. No
      significant associations between O3 and any of the respiratory complaints
      investigated were found. Because of the strong correlation between pollutants, it
      was difficult to identify a single pollutant responsible for the associations
      found in the analyses. This study suggests that the levels of air pollution
      currently experienced in London are linked to short-term increases in the number
      of people visiting accident and emergency departments with respiratory
      complaints.

PMID- 10065666
TI  - Fine particulate air pollution, resuspended road dust and respiratory health
      among symptomatic children.
AB  - The short-term association of particulate air pollution with peak expiratory flow
      rate (PEF) and respiratory symptoms was examined. Forty-nine children with
      chronic respiratory symptoms aged 8-13 yrs were followed daily for six weeks in
      spring, 1995, in Kuopio, Finland. Daily concentrations of particulate material
      with a 50% cut-off aerodynamic diameter < or = 10 microm and < or = 2.5 microm
      (PM10 and PM2.5, respectively), black carbon, and the number concentrations of
      particles from 0.01-10 microm diameter were measured. During the study period,
      PM10 were mainly resuspended soil and street dust, and the concentration was
      estimated using aluminum content of PM10 samples. No consistent effect of
      particles was found as the associations varied by lag. Of the lags examined, only
      1-day lagged PM2.5 was statistically significantly associated with morning PEF
      (beta=-1.06, SE=0.52 (per interquartile increase in pollutant)). Evening PEF was
      significantly associated with the 1-day lagged number of particles in the size
      range 0.1-1.0 microm (beta=-1.56, SE=0.72). One-day lagged PM10, PM2.5-10, PM2.5
      and resuspended PM10, and 4-day average of PM2.5 were significantly associated
      with increased risk of cough. Given the short duration of the study, separating
      the effects of different types of particles was difficult. The present study
      demonstrates the highly variable size and number distribution and chemical
      composition of particles in Finland, and underlines the importance of measuring
      the size and chemical composition of particles to determine which types of
      particles are associated with health effects.

PMID- 10065667
TI  - Airway inflammatory response to ozone in subjects with different asthma severity.
AB  - The aim of this study was to evaluate whether ozone exposure induces a similar
      airway inflammatory response in subjects with different degrees of asthma
      severity. Two groups of asthmatic subjects were studied: seven with intermittent
      mild asthma not requiring regular treatment (group A); and seven with persistent
      mild asthma requiring regular treatment with inhaled corticosteroids and long
      acting beta2-agonists (group B). All subjects were exposed, in a randomized cross
      over design, to air or O3 (0.26 parts per million (ppm) for 2 h with intermittent
      exercise); subjects in group B withdrew from regular treatment 72 h before each
      exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure
      they performed a pulmonary function test, and a questionnaire was completed to
      obtain a total symptom score (TSS). Six hours after the end of the exposure,
      hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages,
      eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the
      sputum supernatant were measured. TSS significantly increased and forced vital
      capacity (FVC) and forced expiratory volume in one second (FEV1) significantly
      decreased after O3 exposure in comparison with air exposure in group A, whereas
      no changes were observed in group B except for a significant decrement of FEV1 2
      h after the beginning of O3 exposure. Sputum neutrophil percentage was
      significantly higher after O3 exposure than after air exposure in both groups
      (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus
      27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O3
      exposure than after air, only in group A. No change due to O3 has been found in
      sputum eosinophil percentage and ECP concentration in both groups. In conclusion,
      the degree of airway response to a short-term exposure to ozone is different in
      subjects with asthma of different severity. The available data do not allow
      elucidation of whether this difference depends on the severity of the disease or
      on the regular anti-inflammatory treatment.

PMID- 10065668
TI  - The economic burden of asthma: direct and indirect costs in Switzerland.
AB  - Asthma mortality increased in Switzerland between 1980 and 1994. This study aimed
      to assess the economic burden of asthma in this country. Chart reviews were
      conducted for the last five patients seen for asthma in physician practices in
      1996 and 1997. Direct expenditures and indirect costs for asthma-related
      morbidity were determined. A total of 589 patient charts were completely
      analysed, including 117 children's charts, obtained from 120 office-based
      physicians. The annual direct medical costs were CHF 1,778 and the mean annual
      indirect costs were CHF 1,019 per patient for all patients. The total estimated
      cost of asthma in Switzerland in 1997 was nearly CHF 1,252 million. Direct
      medical expenditures approached CHF 762 million, or 61% of the total. In 1997,
      the indirect costs for asthma were estimated to have exceeded CHF 490 million. Of
      these costs CHF 123 million (25%) was associated with morbidity and nearly CHF
      368 million (75%) was associated with looking after asthmatic patients who had to
      be cared for at home. This study provides evidence that asthma is a major
      healthcare cost factor in Switzerland, amounting to approximately CHF 1,200
      million per year. The data suggest that cost savings can be achieved by improving
      primary care for asthma in an ambulatory setting.

PMID- 10065669
TI  - Asthma mortality in Russia between 1980 and 1989.
AB  - There is evidence that mortality due to asthma has increased in a number of
      nations over the last two decades. This study was conducted to assess asthma
      mortality rates in Russia from 1980 to 1989. Data obtained were compared with
      figures from other countries. National asthma deaths were obtained from the
      Ministry of Health of the Russian Federation. Age- and sex-specific rates per
      100,000 population per year were adjusted to the European population. Annual
      changes in mortality rates for the study period were estimated by linear
      regression analysis. Between 1980 and 1989, asthma mortality rates per 100,000
      population per year increased from 3.7 to 5.3 in the total Russian population.
      Differences according to age and sex were observed. Asthma deaths increased with
      age and in most cases males showed higher death rates than females. There was a
      statistically significant annual increase in mortality rates for young males < 5
      yrs of age and for adult males aged 35-64 yrs, as well as for females aged > or =
      65 yrs. Asthma mortality rates in Russia between 1980 and 1989 may be considered
      moderate as compared with death rates reported for the same period in other
      countries.

PMID- 10065670
TI  - As-required versus regular nebulized salbutamol for the treatment of acute severe
      asthma.
AB  - Current British guidelines for the administration of beta2-agonists in acute
      severe asthma recommend regular nebulized therapy in hospitalized patients,
      followed by as-required (p.r.n.) use via hand-held devices after discharge. Since
      beta2-agonists do not possess anti-inflammatory activity in vivo, and are thus
      unlikely to influence the rate of recovery from an asthma exacerbation, it was
      hypothesized that patients given the short-acting beta2-agonist salbutamol on an
      as-required basis after admission to hospital would recover as quickly as those
      on regular treatment, but with potential reductions in the total dose delivered.
      Forty-six patients with acute severe asthma were randomly assigned to either
      regular prescriptions of nebulized salbutamol or to usage on a p.r.n. basis, from
      24 h after hospital admission. The primary outcome measures were length of
      hospital stay, time to recovery, and frequency of salbutamol nebulization from 24
      h after admission to discharge. Secondary outcome measures were treatment side
      effects (tremor, palpitations), and patient satisfaction. Length of hospital stay
      was reduced in those patients allocated to p.r.n. salbutamol (geometric mean (GM)
      3.7 days) versus regular salbutamol (GM 4.7 days). Time taken for peak expiratory
      flow to reach 75% of recent best was the same in both groups. There was a highly
      significant reduction in the number of times nebulized therapy was delivered to
      the p.r.n. group (GM 7.0, range 1-30) compared with the regular treatment group
      (GM 14.0, range 4-57; p=0.003; 95% confidence interval for ratio of GMs 1.29
      3.09). In addition, patients reported less tremor (p=0.062) and fewer
      palpitations (p=0.049) in the p.r.n. group. Of the patients in the p.r.n. group
      who had received regular nebulized therapy on previous admissions (n=12), all
      preferred the p.r.n. regimen. Prescribing beta2-agonists on a p.r.n. basis from
      24 h after hospital admission is associated with reduced amount of drug
      delivered, incidence of side-effects, and possibly length of hospital stay. This
      has implications for the efficient use of healthcare resources.

PMID- 10065671
TI  - Dose-response slope of forced oscillation and forced expiratory parameters in
      bronchial challenge testing.
AB  - In population studies, the provocative dose (PD) of bronchoconstrictor causing a
      significant decrement in lung function cannot be calculated for most subjects.
      Dose-response curves for carbachol were examined to determine whether this
      relationship can be summarized by means of a continuous index likely to be
      calculable for all subjects, namely the two-point dose response slope (DRS) of
      mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced
      oscillation technique (FOT). Five doses of carbachol (320 microg each) were
      inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough
      (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria
      (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT
      resistance and forced expiratory volume in one second (FEV1) were measured in
      close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20)
      or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by
      interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained
      as the percentage change at last dose divided by the total dose of carbachol. The
      sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in
      detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or =
      20%) were assessed by receiver operating characteristic (ROC) curves. There were
      23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962;
      p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and
      PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with
      both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of
      the various FOT indices to correctly detect spirometric BHR were as follows:
      DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%,
      Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of
      forced oscillation technique resistance, especially the dose-response slope of
      resistance at 10Hz are proposed as simple quantitative indices of bronchial
      responsiveness which can be calculated for all subjects and that may be useful in
      occupational epidemiology.

PMID- 10065672
TI  - Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization,
      pollen season and bronchial hyperresponsiveness.
AB  - Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic
      rhinitis is associated with asthma and bronchial hyperresponsiveness. To
      determine whether or not nasal and exhaled NO concentrations are increased in
      allergic rhinitis and to assess the relation between hyperresponsiveness and
      exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers
      without upper respiratory tract infection, were randomly selected from a large
      scale epidemiological survey in Central Norway. All were investigated with flow
      volume spirometry, methacholine provocation test, allergy testing and measurement
      of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic
      subjects completed an identical follow-up investigation during the following
      pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the
      nonpollen season, especially in perennially sensitized subjects, as compared with
      controls (p=0.01), and increased further in the pollen season (p=0.04), mainly
      due to a two-fold increase in those with seasonal sensitization. Nasal NO was not
      significantly different from controls in the nonpollen season and did not
      increase significantly in the pollen season. Exhaled NO was increased in
      hyperresponsive subjects, and decreased significantly after methacholine-induced
      bronchoconstriction, suggesting that NO production occurs in the peripheral
      airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen
      exposure, particularly in hyperresponsive subjects, may be suggestive of airway
      inflammation and an increased risk for developing asthma.

PMID- 10065673
TI  - Nasal nitric oxide concentration in paranasal sinus inflammatory diseases.
AB  - In normal upper airways, nitric oxide is generated by the paranasal sinus
      epithelium and then diffuses into the nasal cavities. This study examined whether
      or not nasal NO concentration is affected by paranasal sinus inflammatory
      diseases. The influence of obstruction (nasal polyposis) and/or inflammation
      (allergy or chronic sinusitis) of the paranasal sinuses on nasal NO concentration
      was evaluated in nasal allergic (n=7 patients) or nonallergic (n=20) polyposis,
      nonallergic chronic sinusitis (n=10) and Kartagener's syndrome (n=6) and compared
      with control subjects (n=42). A score of alteration of the paranasal sinus
      (number of altered and occluded sinuses) was determined by a computed tomography
      scan. The nasal NO concentration in nasal nonallergic polyposis (150+/-20 parts
      per billion (ppb)) was significantly decreased compared with both controls (223+/
      6 ppb, p=0.01) and polyposis with allergy (272+/-28 ppb, p<0.0001). In each
      group, the nasal NO concentration was inversely correlated with the extent of
      tomodensitometric alteration of the paranasal sinuses. In Kartagener's syndrome,
      the nasal NO concentration (14+/-2 ppb) was drastically decreased compared with
      all other groups, despite the presence of open paranasal sinuses. Thus, the nasal
      NO concentration in patients with nasal polyposis appeared to be dependent on
      both the allergic status and the degree of obstruction of the paranasal sinuses.

PMID- 10065674
TI  - Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide
      modulation.
AB  - Bradykinin has an important role in asthma pathogenesis, but its site of action
      is unclear. It was previously reported by the authors that bradykinin causes a
      dose-dependent reduction in dynamic compliance but little change in total lung
      resistance. This suggested that bradykinin may have a preferential effect in the
      distant lung. The purpose of the current investigation was to better characterize
      the effects of bradykinin on pulmonary resistance in rodents and explore the role
      of nitric oxide release in modulating the effect of bradykinin. Airway
      constriction was induced in the rats by aerosol administration of bradykinin with
      or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140
      or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)
      monomethyl-L-arginine. Total lung resistance was partitioned into tissue and
      airway resistance by using the alveolar capsule method. Bradykinin induced a
      significant increase in both resistances. Hoe 140 abolished the response to
      bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting
      response. In conclusion, the bradykinin response in the rats was not only
      localized to conducting airways but also involved a relatively selective tissue
      reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation
      of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly
      modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is
      an important modulator of airways responsiveness to bradykinin.

PMID- 10065675
TI  - Orally exhaled nitric oxide levels are related to the degree of blood
      eosinophilia in atopic children with mild-intermittent asthma.
AB  - Increased levels of nitric oxide have been found in expired air of patients with
      asthma, and these are thought to be related to the airway inflammatory events
      that characterize this disorder. Since, in adults, bronchial inflammatory changes
      are present even in mild disease, the present study was designed to evaluate
      whether a significant proportion of children with mild-intermittent asthma could
      have increased exhaled air NO concentrations. Twenty-two atopic children (aged
      11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2
      adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO
      concentrations in orally exhaled air, measured by chemiluminescence, were
      significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per
      billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of
      22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the
      mean in controls). In asthmatic patients, but not in control subjects,
      statistically significant correlations were found between exhaled NO levels and
      absolute number or percentage of blood eosinophils (r=0.63 and 0.56,
      respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not
      correlated with forced expiratory volume in one second (FEV1) or forced
      expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity
      (FVC), either in control subjects, or in asthmatic patients (p>0.1, each
      correlation). These results suggest that a significant proportion of children
      with mild-intermittent asthma may have airway inflammation, as shown by the
      presence of elevated levels of nitric oxide in the exhaled air. The clinical
      relevance of this observation remains to be established.

PMID- 10065676
TI  - Salivary contribution to exhaled nitric oxide.
AB  - Dietary and metabolic nitrate is distributed from the blood to the saliva by
      active uptake in the salivary glands, and is reduced to nitrite in the oral
      cavity by the action of certain bacteria. Since it has been reported that nitric
      oxide may be formed nonenzymatically from nitrite this study aimed to determine
      whether salivary nitrite could influence measurements of exhaled NO. Ten healthy
      subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to
      approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with
      a chemiluminescence technique up to 3 h after the ingestion. Measurements of
      exhaled NO were performed with a single-breath procedure, standardized to a 20-s
      exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values
      of NO were registered as NO release rate (pmol x s(-1)) during the plateau of
      exhalation. Exhaled NO increased steadily over time after nitrate load and a
      maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01),
      whereas no increase was detected in nasal NO levels. Salivary nitrite
      concentrations increased in parallel; at 120 min there was a four-fold increase
      compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite
      reducing conditions in the oral cavity were also manipulated by the use of
      different mouthwash procedures. The antibacterial agent chlorhexidine acetate
      (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading
      and reduced the preload control levels by close to 30% (p<0.05). Sodium
      bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent
      than chlorhexidine acetate. In conclusion, salivary nitric oxide formation
      contributes to nitric oxide in exhaled air and a large intake of nitrate-rich
      foods before the investigation might be misinterpreted as an elevated
      inflammatory activity in the airways. This potential source of error and the
      means for avoiding it should be considered in the development of a future
      standardized method for measurements of exhaled nitric oxide.

PMID- 10065677
TI  - Increased exhaled nitric oxide on days with high outdoor air pollution is of
      endogenous origin.
AB  - The aim of this study was to assess the effect of outdoor air pollution on
      exhaled levels of endogenously released nitric oxide. To exclude bias from
      exogenous NO in the recovered exhaled air (residual NO or NO in dead volume) an
      experimental design was used that sampled NO of endogenous origin only. The
      validity of the presented experimental design was established in experiments
      where subjects were exposed to high levels of exogenous NO (cigarette smoke or
      480 microg x m(-3) synthetic NO). Subsequent 1 min breathing and a final
      inhalation of NO-free air proved to be sufficient to attain pre-exposure values.
      Using the presented method detecting only endogenous NO in exhaled air, 18
      subjects were sampled on 4 separate days with different levels of outdoor air
      pollution (read as an ambient NO level of 4, 30, 138 and 246 microg x m(-3)). On
      the 2 days with highest outdoor air pollution, exhaled NO was significantly
      (p<0.001) increased (67-78%) above the mean baseline value assessed on 4 days
      with virtually no outdoor air pollution. In conclusion, the level of endogenous
      nitric oxide in exhaled air is increased on days with high outdoor air pollution.
      The physiological implications of this findings need to be investigated further.

PMID- 10065678
TI  - Risk factors for lower airway bacterial colonization in chronic bronchitis.
AB  - The aim of this study was to determine the prevalence and risk factors for lower
      airway bacterial colonization (LABC) in stable chronic bronchitis (CB). Forty-one
      outpatients with CB were enrolled in the study (age 63.8+/-9.1 yrs (mean+/-SD);
      forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 62.8+/
      11.2; current/former smokers 24/17). All patients had normal chest radiographs
      and an indication for performing fibreoptic bronchoscopy (pulmonary nodule,
      remote haemoptysis). The protected specimen brush (PSB) was used for bacterial
      sampling, and concentrations > or = 1,000 colony-forming units (cfu) x mL(-1)
      were considered positive for LABC. The repeatability of the procedure in CB was
      assessed in a random subsample of 18 subjects. A 72.2% quantitative agreement was
      found in the repeatability assessment of the PSB technique. Positive PSB
      cultures, obtained in 9 out of 41 (22%) patients, mainly yielded Haemophilus
      influenzae. The logistic regression model, used to determine which variables were
      related to colonization, showed that LABC was associated with current smoking
      (odds ratio (OR) 9.83, confidence interval (CI) 1.16-83.20) and low FVC (OR 0.73,
      CI 0.65-0.81). Age and FEV1 were not related to LABC. It was concluded that the
      prevalence of LABC in stable CB is high (22%), and current smoking is an
      important risk factor.

PMID- 10065679
TI  - Predisposing factors to bacterial colonization in chronic obstructive pulmonary
      disease.
AB  - The aim of this prospective observational study was to determine those factors
      influencing bacterial colonization in patients with stable chronic obstructive
      pulmonary disease (COPD). Eighty-eight outpatients with stable COPD and 20
      patients with normal spirometry and chest radiography (controls) had a fibreoptic
      bronchoscopy performed with topical aerosol anaesthesia. Bacterial colonization
      was determined using the protected specimen brush (PSB) with a cut-off > or =
      10(3) colony-forming units (CFU x mL(-1)). The influence of age, degree of
      airflow obstruction, smoking habit, pack-yrs of smoking, and chest radiographic
      findings on bacterial colonization were assessed by univariate and multivariate
      analysis. Significant bacterial growth was found in 40% of patients and in none
      of the controls. Haemophilus influenzae, Streptococcus viridans, S. pneumoniae
      and Moraxella catarrhalis were the most frequent pathogens. After adjustment for
      other variables, severe airflow limitation (odds ratio (OR) 5.11, 95% confidence
      interval (CI) 1.45-17.9) and current smoking (OR 3.17, 95% CI 2.5-8) remained
      associated with positive bacterial cultures. When only potentially pathogenic
      micro-organisms were considered, significant bacterial growth was found in 30.7%
      of patients, with severe airflow obstruction (OR 9.28, 95% CI 2.19-39.3) being
      the only variable independently associated with positive bacterial cultures. Our
      results show that stable chronic obstructive pulmonary disease patients have a
      high prevalence of bacterial colonization of distal airways which is mainly
      related to the degree of airflow obstruction and cigarette smoking.

PMID- 10065680
TI  - Risk factors for community-acquired pneumonia in adults: a population-based case
      control study.
AB  - Although community-acquired pneumonia (CAP) remains a major cause of
      hospitalization and death, few studies on risk factors have been performed. A
      population-based case-control study of risk factors for CAP was carried out in a
      mixed residential-industrial urban area of 74,610 adult inhabitants in the
      Maresme (Barcelona, Spain) between 1993 and 1995. All patients living in the area
      and clinically suspected of having CAP at primary care facilities and hospitals
      were registered. In total, 205 patients with symptoms, signs and radiographic
      infiltrate compatible with acute CAP participated in the study. They were matched
      by municipality, sex and age with 475 controls randomly selected from the
      municipal census. Risk factors relating the subject's characteristics and habits,
      housing conditions, medical history and treatments were investigated by means of
      a questionnaire. In the univariate analysis, an increased risk of CAP was
      associated with low body mass index, smoking, respiratory infection, previous
      pneumonia, chronic lung disease, lung tuberculosis, asthma, treated diabetes,
      chronic liver disease, and treatments with aminophiline, aerosols and plastic
      pear-spacers. In multivariate models, the only statistically significant risk
      factors were current smoking of >20 cigarettes x day(-1) (odds ratio (OR)=2.77;
      95% confidence interval (CI) 1.14-6.70 compared with never-smokers), previous
      respiratory infection (OR=2.73; 95% CI 1.75-4.26), and chronic bronchitis
      (OR=2.22; 95% CI 1.13-4.37). Benzodiazepines were found to be protective in
      univariate and multivariate analysis (OR=0.46; 95% CI 0.23-0.94). This population
      based study provides new and better established evidence on the factors
      associated with the occurrence of pneumonia in the adult community.

PMID- 10065681
TI  - Bacterial pneumonia as a suprainfection in young adults with measles.
AB  - The aim of this study was to report the clinical and laboratory characteristics
      of bacterial pneumonia related to measles infection, and also to assess any
      correlation between severity and time of onset. Four hundred and twenty-four
      previously healthy young males (age 22+/-2.1 yrs) were hospitalized with typical
      symptoms and signs of measles. One hundred and twelve (26%) developed bacterial
      pneumonia on admission (n=41), during their hospital stay (n=20) or days after
      their discharge (n=51): groups A, B and C, respectively. Single lobar
      consolidation was the most common finding, accounting for 89% of cases. Pleural
      effusion was uncommon and associated in half of the cases with empyema. A
      microbiological diagnosis was made in 81 cases. Streptococcus pneumoniae (65
      cases) and Klebsiella pneumoniae (9 cases) were the most commonly identified
      organisms. Patients from group C had significantly higher values of white blood
      cell count and erythrocyte sedimentation rate, and lower values of arterial
      oxygen tension (14+/-0.8 x 10(9) x L(-1), 88+/-4 mm and 6.3+/-0.4 kPa (47+/-3
      mmHg), respectively) than the other two groups. There were no deaths during the
      hospitalization period. The mean duration of hospital stay was 13+/-2.4 days and
      was longer in the presence of K. pneumoniae infection (19+/-1.6 days). Six
      patients from group C were admitted to the intensive care unit. In conclusion,
      these data suggest that bacterial pneumonia associated with measles is not
      unusual in hospitalized adults, and it seems to be more severe when it occurs
      days after the onset of rash.

PMID- 10065682
TI  - A pilot study of low-dose erythromycin in bronchiectasis.
AB  - Patients with bronchiectasis suffer from sputum production, recurrent
      exacerbations, and progressive airway destruction. Erythromycin is effective in
      diffuse panbronchiolitis, another suppurative airway disorder, although its
      efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo
      controlled study was therefore conducted to evaluate the effects of 8-week
      administration of low dose erythromycin (500 mg b.i.d.) in steady-state
      idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female,
      mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/
      16 yrs) had significantly improved forced expiratory volume in one second, forced
      vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no
      parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and
      IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot
      study show that low-dose erythromycin improves lung function and sputum volume in
      bronchiectasis. Further studies are indicated to evaluate the efficacy of long
      term erythromycin therapy in bronchiectasis.

PMID- 10065683
TI  - Differences in spontaneous breathing pattern and mechanics in patients with
      severe COPD recovering from acute exacerbation.
AB  - The aims of this study were to assess spontaneous breathing patterns in patients
      with chronic obstructive pulmonary disease (COPD) recovering from acute
      exacerbation and to assess the relationship between different breathing patterns
      and clinical and functional parameters of respiratory impairment. Thirty-four
      COPD patients underwent assessment of lung function tests, arterial blood gases,
      haemodynamics, breathing pattern (respiratory frequency (fR), tidal volume (VT),
      inspiratory and expiratory time (tI and tE), duty cycle (tI/ttot), VT/tI) and
      mechanics (oesophageal pressure (Poes), work of breathing (WOB), pressure-time
      product and index, and dynamic intrinsic positive end-expiratory pressure
      (PEEPi,dyn)). According to the presence (group 1) or absence (group 2) of Poes
      swings during the expiratory phase (premature inspiration), 20 (59%) patients
      were included in group 1 and 14 (41%) in group 2. Premature inspirations were
      observed 4.5+/-6.4 times x min(-1) (range 1-31), i.e. 20+/-21% (3.7-100%) of
      total fR calculated from VT tracings. In group 1 the coefficient of variation in
      VT, tE, tI/ttot, PEEPi,dyn, Poes and WOB of the eight consecutive breaths
      immediately preceding the premature inspiration was greater than that of eight
      consecutive breaths in group 2. There were no significant differences in the
      assessed parameters between the two groups in the overall population, whereas
      patients with chronic hypoxaemia in group 1 showed a more severe impairment in
      clinical conditions, mechanics and lung function than hypoxaemic patients in
      group 2. In spontaneously breathing patients with chronic obstructive pulmonary
      disease recovering from an acute exacerbation, detectable activity of inspiratory
      muscles during expiration was found in more than half of the cases. This
      phenomenon was not associated with any significant differences in anthropometric,
      demographic, physiological or clinical characteristics.

PMID- 10065684
TI  - Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary
      disease.
AB  - Pulmonary hyperinflation impairs the function of the diaphragm in patients with
      chronic obstructive pulmonary disease (COPD). However, it has been recently
      demonstrated that the muscle can counterbalance this deleterious effect,
      remodelling its structure (i.e. changing the proportion of different types of
      fibres). The aim of this study was to investigate whether the functional
      impairment present in COPD patients can be associated with structural subcellular
      changes of the diaphragm. Twenty individuals (60+/-9 yrs, 11 COPD patients and 9
      subjects with normal spirometry) undergoing thoracotomy were included.
      Nutritional status and respiratory function were evaluated prior to surgery.
      Then, small samples of the costal diaphragm were obtained and processed for
      electron microscopy analysis. COPD patients showed a mean forced expiratory
      volume in one second (FEV1) of 60+/-9% predicted, a higher concentration of
      mitochondria (n(mit)) in their diaphragm than controls (0.62+/-0.16 versus 0.46+/
      0.16 mitochondrial transections (mt) x microm(-2), p<0.05). On the other hand,
      subjects with air trapping (residual volume (RV)/total lung capacity (TLC) >37%)
      disclosed not only a higher n(mit) (0.63+/-0.17 versus 0.43+/-0.07 mt x microm(
      2), p<0.05) but shorter sarcomeres (L(sar)) than subjects without this functional
      abnormality (2.08+/-0.16 to 2.27+/-0.15 microm, p<0.05). Glycogen stores were
      similar in COPD and controls. The severity of airways obstruction (i.e. FEV1) was
      associated with n(mit) (r=-0.555, p=0.01), while the amount of air trapping (i.e.
      RV/TLC) was found to correlate with both n(mit) (r=0.631, p=0.005) and L(sar) (r=
      0.526, p<0.05). Finally, maximal inspiratory pressure (PI,max) inversely
      correlated with n(mit) (r=-0.547, p=0.01). In conclusion, impairment in lung
      function occurring in patients with chronic obstructive pulmonary disease is
      associated with subcellular changes in their diaphragm, namely a shortening in
      the length of sarcomeres and an increase in the concentration of mitochondria.
      These changes form a part of muscle remodelling, probably contributing to a
      better functional muscle behaviour.

PMID- 10065685
TI  - Long-term recovery of diaphragm strength in neuralgic amyotrophy.
AB  - Diaphragm paralysis is a recognized complication of neuralgic amyotrophy that
      causes severe dyspnoea. Although recovery of strength in the arm muscles, when
      affected, is common, there are little data on recovery of diaphragm function.
      This study, therefore, re-assessed diaphragm strength in cases of bilateral
      diaphragm paralysis due to neuralgic amyotrophy that had previously been
      diagnosed at the authors institutions. Fourteen patients were recalled between 2
      and 11 yrs after the original diagnosis. Respiratory muscle and diaphragm
      strength were measured by volitional manoeuvres as maximal inspiratory pressure
      and sniff transdiaphragmatic pressure. Cervical magnetic phrenic nerve
      stimulation was used to give a nonvolitional measure of diaphragm strength:
      twitch transdiaphragmatic pressure. Only two patients remained severely
      breathless. Ten of the 14 patients had evidence of some recovery of diaphragm
      strength, in seven cases to within 50% of the lower limit of normal. The rate of
      recovery was variable: one patient had some recovery after 2 yrs, and the rest
      took 3 yrs or more. In conclusion, in most patients with diaphragm paralysis due
      to neuralgic amyotrophy, some recovery of the diaphragm strength occurs, but the
      rate of recovery may be slow.

PMID- 10065686
TI  - Diaphragm electromyogram measured with unilateral magnetic stimulation.
AB  - The purpose of this study was to establish the phrenic nerve conduction time
      (PNCT) for magnetic stimulation and further assess the relatively new technique
      of anterior unilateral magnetic stimulation (UMS) of the phrenic nerves in
      evaluating the diaphragm electromyogram (EMG). An oesophageal electrode was used
      to record the diaphragm compound muscle action potential (CMAP) elicited by
      supramaximal percutaneous electrical phrenic nerve stimulation (ES) and UMS from
      eight normal subjects. The oesophageal electrode used for recording the CMAP was
      positioned at the level of the hiatus and 3 cm below. The diaphragm CMAP was also
      recorded from chest wall surface electrodes in five subjects. All of the phrenic
      nerves could be maximally stimulated with UMS. A clear plateau of the amplitude
      of the CMAP was achieved for the right and left phrenic nerves. The mean
      amplitudes of the CMAP recorded from the oesophageal electrode were, for the
      right side, 0.74+/-0.29 mV (mean+SD) for ES and 0.76+/-0.30 mV for UMS with
      maximal power output, and for the left side 0.88+/-0.33 mV for ES and 0.80+/-0.24
      mV for UMS. PNCT measured by the oesophageal electrode with ES and UMS with
      maximal output were, for the right side, 7.0+/-0.8 ms and 6.9+/-0.8 ms,
      respectively, and for the left side 7.8+/-1.2 ms and 7.7+/-1.3 ms, respectively.
      However, the CMAP recorded from chest wall surface electrodes with UMS was
      unsuitable for the measurement of PNCT. The results suggest that unilateral
      magnetic stimulation of the phrenic nerves combined with an oesophageal electrode
      can be used to assess diaphragmatic electrical activity and measure the phrenic
      nerve conduction time.

PMID- 10065687
TI  - Effects of dilated cardiomyopathy on the diaphragm in the Syrian hamster.
AB  - This study aimed to elucidate changes in respiratory muscles and their mechanism
      in cardiomyopathy. The contractile properties and histology of the diaphragm, as
      well as serum levels of insulin-like growth factor (IGF)-1, were examined in 10
      hamsters with idiopathic dilated cardiomyopathy (CM) and 10 controls. At 28
      weeks, body weight in CM was reduced compared with controls (114+/-10 versus
      144+/-14 g, p<0.0001). The ratio of diaphragm to body weight was significantly
      higher in CM than in controls (0.228+/-0.015 versus 0.182+/-0.017, p<0.0001). In
      vitro, maximal diaphragmatic twitch (303+/-63 versus 455+/-119 g x cm(-2)) and
      tetanic tensions (1,555+/-369 versus 2,204+/-506 g x cm(-2)) were significantly
      lower in CM than in controls (p<0.005). The half-relaxation time was
      significantly shorter in CM (19+/-1 ms) than in controls (24+/-3 ms, p<0.0005).
      Fatiguability at 25 Hz was significantly less in CM (28%) than in controls (42%,
      p<0.0001). Diaphragm and gastrocnemius adenosine triphosphatase staining showed
      type I fibre atrophy in CM, associated with an increase in the number of type I
      fibres in the diaphragm. Histological examination of both muscles revealed an
      abnormal muscular pattern. Finally, serum levels of IGF-1 were 47% lower in the
      CM group than in controls (p<0.0001) and were clearly related to the changes in
      the contractile properties and histology of the diaphragm. In conclusion,
      cardiomyopathy in hamsters: 1) depressed the force-generating capacity and
      shortened the relaxation of the hamster diaphragm; 2) induced type I fibre
      atrophy in combination with a myopathic pattern; and 3) was associated with a
      significant reduction in serum levels of insulin-like growth factor-1, related to
      the diaphragmatic changes. Whether these changes are primary myopathic or
      secondary to heart failure remains to be elucidated.

PMID- 10065688
TI  - Effect of obesity and erect/supine posture on lateral cephalometry: relationship
      to sleep-disordered breathing.
AB  - Craniofacial and upper airway anatomy, obesity and posture may all play a role in
      compromising upper airway patency in patients with the sleep apnoea/hypopnoea
      syndrome. The aim of this study was to investigate the relationship between
      obesity, facial structure and severity of sleep-disordered breathing using
      lateral cephalometric measurements and to assess the effect of body posture on
      cephalometric measurements of upper airway calibre variables in obese and non
      obese subjects. Lateral cephalometry was carried out in erect and supine postures
      in 73 awake male subjects randomly selected from patients referred for
      polysomnography who had a wide range of apnoea/hypopnoea frequencies (1-131
      events x h sleep(-1)). Subjects were divided into non-obese (body mass index
      (BMI) < 30 kg x m(-2); n=42) and obese (BMI > or = 30 kg x m(-2); n=31) groups.
      Significant but weak correlations were found between apnoea/hypopnoea index (AHI)
      and measurements reflecting upper airway dimensions: uvular protrusion-posterior
      pharyngeal wall (r=-0.26, p<0.05) and hyoid-posterior pharyngeal wall (r=0.26,
      p<0.05). Multiple regression using both upper airway dimensions improved the
      correlation to AHI (r=0.34, p=0.01). Obese subjects had greater hyoid-posterior
      pharyngeal wall distances than non-obese subjects, both erect (42+/-5 versus 39+/
      4 mm, respectively (mean+/-SD) p<0.01) and supine (43+/-5 versus 40+/-4 mm,
      p<0.05). Skeletal craniofacial structure was similar in obese and non-obese
      subjects. In conclusion, measurements reflecting upper airway size were
      correlated with the severity of sleep-disordered breathing. Differences in upper
      airway size measurements between obese and non-obese subjects were independent of
      bony craniofacial structure.

PMID- 10065689
TI  - Cephalometric abnormalities in non-obese and obese patients with obstructive
      sleep apnoea.
AB  - The aim of this work was to comprehensively evaluate the cephalometric features
      in Japanese patients with obstructive sleep apnoea (OSA) and to elucidate the
      relationship between cephalometric variables and severity of apnoea. Forty-eight
      cephalometric variables were measured in 37 healthy males and 114 male OSA
      patients, who were classed into 54 non-obese (body mass index (BMI) <27 kg x m(
      2), apnoea-hypopnoea index (AHI)=25.3+/-16.1 events x h(-1)) and 60 obese (BMI >
      or = 27 kg x m(-2), AHI=45.6+/-28.0 events h(-1)) groups. Diagnostic
      polysomnography was carried out in all of the OSA patients and in 19 of the
      normal controls. The non-obese OSA patients showed several cephalometric defects
      compared with their BMI-matched normal controls: 1) decreased facial A-P distance
      at cranial base, maxilla and mandible levels and decreased bony pharynx width; 2)
      enlarged tongue and inferior shift of the tongue volume; 3) enlarged soft palate;
      4) inferiorly positioned hyoid bone; and 5) decreased upper airway width at four
      different levels. More extensive and severe soft tissue abnormalities with a few
      defects in craniofacial bony structures were found in the obese OSA group. For
      the non-obese OSA group, the stepwise regression model on AHI was significant
      with two bony structure variables as determinants: anterior cranial base length
      (S-N) and mandibular length (Me-Go). Although the regression model retained only
      linear distance between anterior vertebra and hyoid bone (H-VL) as an explainable
      determinant for AHI in the obese OSA group, H-VL was significantly correlated
      with soft tissue measurements such as overall tongue area (Ton), inferior tongue
      area (Ton2) and pharyngeal airway length (PNS-V). In conclusion, Japanese
      obstructive sleep apnoea patients have a series of cephalometric abnormalities
      similar to those described in Caucasian patients, and that the aetiology of
      obstructive sleep apnoea in obese patients may be different from that in non
      obese patients. In obese patients, upper airway soft tissue enlargement may play
      a more important role in the development of obstructive sleep apnoea, whereas in
      non-obese patients, bony structure discrepancies may be the dominant contributing
      factors for obstructive sleep apnoea.

PMID- 10065690
TI  - Craniofacial modifications in children with habitual snoring and obstructive
      sleep apnoea: a case-control study.
AB  - Habitual snoring and obstructive sleep apnoea in children, which are frequently
      associated with adenotonsillar hypertrophy, may begin early in life and in
      relation with orocraniofacial features. The aim of this study was to detect the
      presence of early bone craniofacial modifications in young children with a long
      history of habitual snoring. Twenty-six habitually snoring children (mean age 4.6
      yrs) were studied by nocturnal portable recording or diurnal polysomnography,
      cephalometry and orthodontic evaluation. A comparison of cephalometric findings
      was made between the studied group and 26 age-matched children (mean age 5.1 yrs)
      with no history of snoring or respiratory problems during sleep. The
      cephalometric analyses showed a significant increase in craniomandibular
      intermaxillar, lower and upper goniac angles with a retroposition and posterior
      rotation of the mandible (high angle face) and a reduction in the rhinopharynx
      space caused by higher thickness of adenoids in habitually snoring children
      compared with controls. Cross-bites and labial incompetence as well as daytime
      symptoms and familiarity for habitual snoring were found in most of the studied
      group of snorers compared with controls. The results indicate that upper airway
      obstruction during sleep is associated with mild but significant cephalometric
      and craniofacial modifications in children complaining of habitual snoring.
      Whether this skeletal conformation is genetically determined or influenced by the
      early onset of habitual snoring remains to be assessed.

PMID- 10065691
TI  - Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients
      with obstructive sleep apnoea syndrome.
AB  - In the present study, respiratory drives to chemical stimuli and peripheral
      chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS).
      The effects of oral administration of domperidone, a selective dopamine D2
      receptor antagonist, were also examined, to study the respiratory effects of
      endogenous dopamine on peripheral chemoreceptors. Sixteen patients with OSAS and
      nine normal control subjects were studied. Respiratory responses to hypercapnia
      and hypoxia were measured using the rebreathing method and isocapnic progressive
      hypoxia method, respectively. The hypoxic withdrawal test, which measures the
      decrease in ventilation caused by two breaths of 100% O2 under mild hypercapnic
      hypoxic conditions (end-tidal oxygen and carbon dioxide tensions approximately
      8.0 kPa and 5.3-6.7 kPa, respectively), was used to evaluate peripheral
      chemosensitivity. In the patients with OSAS, ventilatory responses to hypercapnia
      and hypoxia were significantly decreased compared with those of control subjects.
      Hypoxic withdrawal tests showed that peripheral chemosensitivity was
      significantly lower in patients with OSAS than in normal subjects. Hypercapnic
      ventilatory response and peripheral chemosensitivity were enhanced by
      administration of domperidone in the patients with OSAS, although no changes in
      either of these were observed in the control subjects. The hypoxic ventilatory
      response and peripheral chemosensitivity in the patients with OSAS were each
      significantly correlated with severity of hypoxia during sleep. These findings
      suggest that peripheral chemosensitivity in patients with obstructive sleep
      apnoea syndrome may be decreased as a result of abnormality in dopaminergic
      mechanisms and that the reduced chemosensitivity observed in patients with
      obstructive sleep apnoea syndrome may affect the severity of hypoxia during
      sleep.

PMID- 10065692
TI  - Trimodality therapy in stage III non-small cell lung cancer: prediction of
      recurrence by assessment of p185neu.
AB  - In a trimodality treatment approach for stage III non-small cell lung cancer the
      prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four
      patients were admitted to chemotherapy followed by twice-daily radiation with
      concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical
      assessment of p185neu expression was performed in paraffin-embedded mediastinal
      lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin
      embedded biopsies of mediastinal lymph node metastases were available in 33
      cases. Seven out of eight patients with positive p185neu staining developed
      distant metastases, in contrast to seven out of 25 negative cases. Expression of
      p185neu in mediastinal lymph node metastases was a significant predictor for
      progression-free survival (p=0.047) and resulted mainly from significant
      differences in metastases-free survival (p185neu-positive versus p185neu
      negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40%
      and 32%; p=0.04). On the basis of these preliminary results it was concluded that
      further evaluation of p185neu expression in trials on neoadjuvant and adjuvant
      therapy is warranted. When the prognostic impact of p185neu in such trials with
      larger patient numbers is confirmed, this may contribute to the identification of
      stratification variables for future treatment approaches of non-small cell lung
      cancer.

PMID- 10065693
TI  - Do morphology and stage explain the inferior lung cancer survival in Denmark?
AB  - Danish lung cancer patients diagnosed during 1983-1987 experienced 5-yr relative
      survival rates 2-7% inferior to patients in the other Nordic countries, despite
      the similarity of cancer registration and healthcare systems in the Nordic
      countries. Is the inferior relative survival in Denmark due to differences in
      morphology or stage of lung cancers? The present study compared in detail the
      survival of 92,719 patients diagnosed with lung cancer during 1978-1992 in
      Denmark, Finland, and Norway. In particular, differences in morphology and extent
      of disease were studied. A poor survival rate for small cell anaplastic lung
      carcinoma compared with all other morphologies was confirmed. However, this could
      not explain the relative survival differences observed between countries. Extent
      of disease was the most important predictor of survival. Part of the observed
      survival differences could be explained by a less favourable stage distribution
      in Denmark, combined with a slightly lower relative survival rate for those with
      metastatic disease. Differences in treatment are unlikely to explain the
      findings, although delays in diagnosing and treating patients in Denmark compared
      with neighbouring countries could partially explain the lower patient survival in
      Denmark. In conclusion, the main factor in the lower survival rate in Denmark is
      unfavourable stage distribution.

PMID- 10065694
TI  - An epidemiological study of lung cancer: history and histological types in a
      general population in northern Finland.
AB  - A prospective epidemiological study was conducted to assess the incidence,
      diagnosis, histology and surgical treatment of lung cancer in northern Finland.
      The results were compared with those obtained in a similar survey 20 yrs earlier.
      Most of the patients with a suspected lung tumour were interviewed (72%) and the
      information was combined with that obtained from the national cancer registry.
      All pathological specimens were re-evaluated by a pathologist. A total of 602 new
      lung cancer cases (85% male, 15% female) were diagnosed during the years 1990
      1992, the annual incidence per 100,000 being 63 for males and 9.5 for females.
      The number not reported to the Finnish Cancer Registry was low (<1%). Lung cancer
      was confirmed histologically in 381 cases (63%) and in addition cytologically in
      135 cases (23%). Squamous cell carcinoma was the most common histological type
      (40%), the proportion of adenocarcinoma being 26%, small cell carcinoma 24% and
      large cell carcinoma 4%. The incidence of lung cancer had decreased significantly
      among males (from 87 to 63 per 100,000) compared with 20 yrs earlier but had
      increased among females (from 4.1 to 9.5), chiefly on account of adenocarcinoma.
      The findings of this prospective study show an increase in the incidence of lung
      adenocarcinoma among females, a histological type which is less closely related
      to smoking than the other cancers. This suggests that other risk factors may play
      an increasing role in the aetiology of lung cancer.

PMID- 10065695
TI  - Surgical treatment of hydatid cyst of the lung: review of 30 cases.
AB  - Hydatid cyst disease is still a problem in Turkey, especially in the east
      Anatolian region, as well as in many other places in the world. A retrospective
      review was made of the surgical treatment of 30 patients with pulmonary hydatid
      cysts during the last 3 yrs. Nineteen patients were male and 11 female with an
      average age of 23.5 yrs (range 4-44 yrs). Cystotomy and capitonnage were
      performed in 28 of the 30 cases (93.4%). The transdiaphragmatic route or
      simultaneous laparotomy was preferred when the liver was involved. Albendazole
      was used in four patients with multiple hydatid cyst due to probable recurrence
      in the postoperative period. Cough and chest pain were the prominent symptoms in
      the majority of cases. A single lobe was affected in 22 patients. Unilateral
      multiple foci were present in four patients and bilateral multiple foci in four.
      Six patients had concomitant liver cysts. Morbidity was low and no mortality was
      seen. No recurrences were seen on control chest radiographs during the last 2-yr
      follow-up. In the treatment of hydatid cyst of the lung, conservative surgical
      methods such as cystotomy and capitonnage still remain the treatment of choice.
      Medical treatment could be used for prophylactic purposes and in some instances,
      but the percutaneous aspiration method should not be performed.

PMID- 10065696
TI  - The contribution of the swallowed fraction of an inhaled dose of salmeterol to it
      systemic effects.
AB  - Salmeterol is approximately eight times as potent as salbutamol for systemic
      effects. This may be because the drug is eight times more potent on receptors or
      there may be differences in systemic bioavailability. The systemic effects of
      salbutamol are limited by its fairly high first-pass metabolism, but the oral
      bioavailability of salmeterol is unknown. The contribution of the swallowed
      fraction of an inhaled dose of salmeterol to its systemic effects were analysed
      in a randomized, double-blind, crossover study. Twelve healthy subjects were
      given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral
      activated charcoal or inhaled placebo plus oral activated charcoal on three
      separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate
      (QTc), plasma potassium and glucose concentrations were measured for 4 h
      following the inhaled drug. Salmeterol with and without oral charcoal produced
      significant changes for all measures compared to placebo. The magnitude of effect
      following salmeterol alone was significantly greater than that following
      salmeterol plus charcoal for fC and glucose (mean (95% confidence interval)
      differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1),
      respectively) and nonsignificantly greater for QTc interval and potassium
      concentration. The differences between salmeterol given with and without charcoal
      suggest that 28-36% of the systemic response to salmeterol administered from a
      metered-dose inhaler are due to drug absorbed from the gastrointestinal tract.
      Thus, most of the systemic effects are due to the inhaled fraction of the drug.

PMID- 10065697
TI  - Respiratory muscle involvement in multiple sclerosis.
AB  - Respiratory complications are common in the terminal stages of multiple sclerosis
      and contribute to mortality in these patients. When respiratory motor pathways
      are involved, respiratory muscle weakness frequently occurs. Although it is well
      established that weakness of the respiratory muscles produces a restrictive
      ventilatory defect, the degree of muscle weakness and pulmonary function are
      poorly related. Respiratory muscle weakness was observed in patients with normal
      or near normal pulmonary function. Expiratory muscle weakness is more prominent
      than inspiratory muscle weakness and may impair performance of coughing.
      Subsequently, in addition to bulbar dysfunction, respiratory muscle weakness may
      contribute to ineffective coughing, pneumonia, and sometimes even acute
      ventilatory failure may ensue. Respiratory muscle weakness may also occur early
      in the course of the disease. Recent studies suggest that the respiratory muscles
      can be trained for both strength and endurance in multiple sclerosis patients.
      Whether respiratory muscle training delays the development of respiratory
      dysfunction and subsequently improves exercise capacity and cough efficacy,
      prevents pulmonary complications or prolongs survival in the long-term remains to
      be determined.

PMID- 10065698
TI  - Cough, dyspnoea and purulent sputum in a 66-yr-old nonsmoking female.

PMID- 10065699
TI  - Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a
      causal relationship?
AB  - Lung injury caused by intrauterine inflammation has recently been strongly
      implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article
      supports this theory by suggesting a causative role of intrauterine
      cytomegalovirus (CMV) infection for the development of WMS. A male premature
      infant, born at 33 weeks of gestational age, developed chronic lung disease
      compatible with WMS and diagnostic evaluation was positive for CMV infection.
      High-resolution computed tomography scan and lung histology revealed typical
      features of WMS in association with signs of interstitial pneumonia. CMV was
      found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from
      open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed
      resolving lung disease at the age of 6, 10 and 16 months, with lung function
      signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus
      pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that
      intrauterine cytomegalovirus infection caused a pattern of lung injury consistent
      with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be
      investigated as to a possible role of congenital infection.

PMID- 10065700
TI  - Late massive haemoptyses from bronchopulmonary collaterals in infarcted segments
      following pulmonary embolism.
AB  - Massive, recurrent haemoptyses requiring blood transfusions occurred in a patient
      who had been diagnosed as having pulmonary thromboembolism 3 months earlier. To
      the authors' knowledge this is the first case report of this kind, in which
      massive haemoptyses were proved to be caused by large bronchopulmonary
      collaterals that had developed in the infarcted lung segments affected by
      embolism. Selective embolization of the collaterals proved to be therapeutic and
      life saving.

PMID- 10065701
TI  - Rupture of aortic aneurysm with right-sided haemothorax.
AB  - A 62-yr-old male with a history of high blood pressure was admitted for
      persistent dyspnoea and a right-sided pleural effusion, complicated by a recent
      episode of shock. There was no history of trauma and the patient denied any
      thoracic pain. A chest tube was inserted which released nonclotting bloody fluid.
      A thoracic computed tomographic scan of the chest revealed an aneurysm of the
      inferior third of the descending thoracic aorta. The patient underwent a
      successful prosthetic graft replacement. We emphasize that rupture of aortic
      aneurysms should be considered in the evaluation of spontaneous haemothorax even
      if it is right-sided and not associated with pain.

PMID- 10065702
TI  - Human lung volumes and the mechanisms that set them.
AB  - Definitions of human lung volumes and the mechanisms that set them are reviewed
      in the context of pulmonary function testing, with attention to the distinction
      between functional residual capacity (FRC) and the static relaxation volume of
      the respiratory system, and to the circumstances in which FRC and residual volume
      are set by dynamic rather than by static mechanisms. Related terms, conventions,
      and issues are addressed, including some common semantic and conceptual
      difficulties, with attention to "gas trapping", "hyperinflation", and
      "restriction".

PMID- 10065703
TI  - Inhaled oxitropium bromide is currently used as the first-line therapy of
      patients with chronic pulmonary disease in Japan.

PMID- 10065704
TI  - Machine learning approaches for the prediction of signal peptides and other
      protein sorting signals.
AB  - Prediction of protein sorting signals from the sequence of amino acids has great
      importance in the field of proteomics today. Recently, the growth of protein
      databases, combined with machine learning approaches, such as neural networks and
      hidden Markov models, have made it possible to achieve a level of reliability
      where practical use in, for example automatic database annotation is feasible. In
      this review, we concentrate on the present status and future perspectives of
      SignalP, our neural network-based method for prediction of the most well-known
      sorting signal: the secretory signal peptide. We discuss the problems associated
      with the use of SignalP on genomic sequences, showing that signal peptide
      prediction will improve further if integrated with predictions of start codons
      and transmembrane helices. As a step towards this goal, a hidden Markov model
      version of SignalP has been developed, making it possible to discriminate between
      cleaved signal peptides and uncleaved signal anchors. Furthermore, we show how
      SignalP can be used to characterize putative signal peptides from an archaeon,
      Methanococcus jannaschii. Finally, we briefly review a few methods for predicting
      other protein sorting signals and discuss the future of protein sorting
      prediction in general.

PMID- 10065705
TI  - Structural motif of phosphate-binding site common to various protein
      superfamilies: all-against-all structural comparison of protein-mononucleotide
      complexes.
AB  - In order to search for a common structural motif in the phosphate-binding sites
      of protein-mononucleotide complexes, we investigated the structural variety of
      phosphate-binding schemes by an all-against-all comparison of 491 binding sites
      found in the Protein Data Bank. We found four frequently occurring structural
      motifs composed of protein atoms interacting with phosphate groups, each of which
      appears in different protein superfamilies with different folds. The most
      frequently occurring motif, which we call the structural P-loop, is shared by 13
      superfamilies and is characterized by a four-residue fragment, GXXX, interacting
      with a phosphate group through the backbone atoms. Various sequence motifs,
      including Walker's A motif or the P-loop, turn out to be a structural P-loop
      found in a few specific superfamilies. The other three motifs are found in pairs
      of superfamilies: protein kinase and glutathione synthetase ATPase domain like,
      actin-like ATPase domain and nucleotidyltransferase, and FMN-linked
      oxidoreductase and PRTase.

PMID- 10065706
TI  - A neural network based predictor of residue contacts in proteins.
AB  - We describe a method based on neural networks for predicting contact maps of
      proteins using as input chemicophysical and evolutionary information. Neural
      networks are trained on a data set comprising the contact maps of 200 non
      homologous proteins of well resolved three-dimensional structures. The systems
      learn the association rules between the covalent structure of each protein and
      its correspondent contact map by means of a standard back propagation algorithm.
      Validation of the predictor on the training set and on 408 proteins of known
      structure which are not homologous to those contained in the training set
      indicate that this method scores higher than statistical approaches previously
      described and based on correlated mutations and sequence information.

PMID- 10065707
TI  - Amino acid composition of protein termini are biased in different manners.
AB  - An exhaustive statistical analysis of the amino acid sequences at the carboxyl
      (C) and amino (N) termini of proteins and of coding nucleic acid sequences at the
      5' side of the stop codons was undertaken. At the N ends, Met and Ala residues
      are over-represented at the first (+1) position whereas at positions 2 and 5 Thr
      is preferred. These peculiarities at N-termini are most probably related to the
      mechanism of initiation of translation (for Met) and to the mechanisms governing
      the life-span of proteins via regulation of their degradation (for Ala and Thr).
      We assume that the C-terminal bias facilitates fixation of the C ends on the
      protein globule by a preference for charged and Cys residues. The terminal
      biases, a novel feature of protein structure, have to be taken into account when
      molecular evolution, three-dimensional structure, initiation and termination of
      translation, protein folding and life-span are concerned. In addition, the bias
      of protein termini composition is an important feature which should be considered
      in protein engineering experiments.

PMID- 10065708
TI  - Recognizing misfolded and distorted protein structures by the assumption-based
      similarity score.
AB  - A new similarity score (sigma-score) is proposed which is able to find the
      correct protein structure among the very close alternatives and to distinguish
      between correct and deliberately misfolded structures. This score is based on the
      general principle 'similar likes similar', and it favors hydrophobic and
      hydrophilic contacts, and disfavors hydrophobic-to-hydrophilic contacts in
      proteins. The values of sigma-scores calculated for the high-resolution protein
      structures from the representative set are compared with those of alternatives:
      (i) very close alternatives which are only slightly distorted by conformational
      energy minimization in vacuo; (ii) alternatives with subsequently growing
      distortions, generated by molecular dynamics simulations in vacuo; (iii)
      structures derived by molecular dynamics simulation in solvent at 300 K; (iv)
      deliberately misfolded protein models. In nearly all tested cases the similarity
      score can successfully distinguish between experimental structure and its
      alternatives, even if the root mean square displacement of all heavy atoms is
      less than 1 A. The confidence interval of the similarity score was estimated
      using the high-resolution X-ray structures of domain pairs related by non
      crystallographic symmetry. The similarity score can be used for the evaluation of
      the general quality of the protein models, choosing the correct structures among
      the very close alternatives, characterization of models simulating
      folding/unfolding, etc.

PMID- 10065709
TI  - Analysis of protein-protein interactions by mutagenesis: direct versus indirect
      effects.
AB  - Site-directed mutagenesis, including double-mutant cycles, is used routinely for
      studying protein-protein interactions. We now present a case analysis of
      chymotrypsin inhibitor 2 (CI2) and subtilisin BPN' using (i) a residue in CI2
      that is known to interact directly with subtilisin (Tyr42) and (ii) two CI2
      residues that do not have direct contacts with subtilisin (Arg46 and Arg48). We
      find that there are similar changes in binding energy on mutation of these two
      sets of residues. It can thus be difficult to interpret mutagenesis data in the
      absence of structural information.

PMID- 10065710
TI  - Directed evolution converts subtilisin E into a functional equivalent of
      thermitase.
AB  - We used directed evolution to convert Bacillus subtilis subtilisin E into an
      enzyme functionally equivalent to its thermophilic homolog thermitase from
      Thermoactinomyces vulgaris. Five generations of random mutagenesis, recombination
      and screening created subtilisin E 5-3H5, whose half-life at 83 degrees C (3.5
      min) and temperature optimum for activity (Topt, 76 degrees C) are identical with
      those of thermitase. The Topt of the evolved enzyme is 17 degrees C higher and
      its half-life at 65 degrees C is >200 times that of wild-type subtilisin E. In
      addition, 5-3H5 is more active towards the hydrolysis of succinyl-Ala-Ala-Pro-Phe
      p-nitroanilide than wild-type at all temperatures from 10 to 90 degrees C.
      Thermitase differs from subtilisin E at 157 amino acid positions. However, only
      eight amino acid substitutions were sufficient to convert subtilisin E into an
      enzyme equally thermostable. The eight substitutions, which include known
      stabilizing mutations (N218S, N76D) and also several not previously reported, are
      distributed over the surface of the enzyme. Only two (N218S, N181D) are found in
      thermitase. Directed evolution provides a powerful tool to unveil mechanisms of
      thermal adaptation and is an effective and efficient approach to increasing
      thermostability without compromising enzyme activity.

PMID- 10065711
TI  - The role of the flap residue, threonine 77, in the activation and catalytic
      activity of pepsin A.
AB  - Flexible loops, often referred to as flaps, have been shown to play a role in
      catalytic mechanisms of different enzymes. Flaps at the active site regions have
      been observed in the crystal structures of aspartic proteinases and their
      residues implicated in the catalytic processes. This research investigated the
      role of the flap residue, threonine 77, in the activation of pepsinogen and the
      catalytic mechanism of pepsin. Three mutants, T77S, T77V and T77G, were
      constructed. Differences in amino acid polarity and hydrogen bonding potential
      were shown to have an influence on the activation and catalytic processes. T77S
      activated at the same rate and had similar catalytic parameters as the wild-type
      pepsin. The activation rates of T77V and T77G were slower and their catalytic
      efficiencies lower than the wild-type. The results demonstrated that the
      threonine 77 polar side chain played a role in a proteolysis. The contribution of
      the side chain to zymogen activation was associated with the proteolytic cleavage
      of the prosegment. It was postulated that the hydroxyl group at position 77
      provided an essential hydrogen bond that contributed to proper substrate
      alignment and, indirectly, to a catalytically favorable geometry of the
      transition state.

PMID- 10065712
TI  - Engineering a chimeric pyrroloquinoline quinone glucose dehydrogenase:
      improvement of EDTA tolerance, thermal stability and substrate specificity.
AB  - An engineered Escherichia coli PQQ glucose dehydrogenase (PQQGDH) with improved
      enzymatic characteristics was constructed by substituting and combining the gene
      encoding protein regions responsible for EDTA tolerance, thermal stability and
      substrate specificity. The protein region responsible for complete EDTA tolerance
      in Acinetobacter calcoaceticus, which is recognized as the indicator of high
      stability in co-factor binding, was elucidated. The region is located between 32
      and 59% from the N-terminus of A. calcoaceticus PQQGDH(A27 region) and also
      corresponds to the same position from 32 to 59% from the N-terminus in E. coli
      PQQGDH, though E. coli PQQGDH is EDTA sensitive. We previously reported that the
      C-terminal 3% region of A. calcoaceticus (A3 region) played an important role in
      the increase of thermal stability, and that His775Asn substitution in E. coli
      PQQGDH resulted in an increase in the substrate specificity of E. coli PQQGDH
      towards glucose. Based on these findings, chimeric and/or mutated PQQGDHs, E97A3
      H775N, E32A27E41 H782N, E32A27E38A3 and E32A27E38A3 H782N were constructed to
      investigate the compatibility of two protein regions and one amino acid
      substitution. His775 substitution to Asn corresponded to His782 substitution to
      Asn (H782N) in chimeric enzymes harbouring the A27 region. Since all the chimeric
      PQQGDHs harbouring the A27 region were EDTA tolerant, the A27 region was found to
      be compatible with the other region and substituted amino acid responsible for
      the improvement of enzymatic properties. The contribution of the A3 region to
      thermal stability complemented the decrease in the thermal stability due to the
      His775 or His782 substitution to Asn. E32A27E38A3 H782N, which harbours all the
      above mentioned three regions, showed improved EDTA tolerance, thermal stability
      and substrate specificity. These results suggested a strategy for the
      construction of a semi-artificial enzyme by substituting and combining the gene
      encoding protein regions responsible for the improvement of enzyme
      characteristics. The characteristics of constructed chimeric PQQGDH are discussed
      based on the predicted model, beta-propeller structure.

PMID- 10065713
TI  - Characterization of functional residues in the interfacial recognition domain of
      lecithin cholesterol acyltransferase (LCAT).
AB  - Lecithin cholesterol acyltransferase (LCAT) is an interfacial enzyme active on
      both high-density (HDL) and low-density lipoproteins (LDL). Threading alignments
      of LCAT with lipases suggest that residues 50-74 form an interfacial recognition
      site and this hypothesis was tested by site-directed mutagenesis. The (delta56
      68) deletion mutant had no activity on any substrate. Substitution of W61 with F,
      Y, L or G suggested that an aromatic residue is required for full enzymatic
      activity. The activity of the W61F and W61Y mutants was retained on HDL but
      decreased on LDL, possibly owing to impaired accessibility to the LDL lipid
      substrate. The decreased activity of the single R52A and K53A mutants on HDL and
      LDL and the severer effect of the double mutation suggested that these conserved
      residues contribute to the folding of the LCAT lid. The membrane-destabilizing
      properties of the LCAT 56-68 helical segment were demonstrated using the
      corresponding synthetic peptide. An M65N-N66M substitution decreased both the
      fusogenic properties of the peptide and the activity of the mutant enzyme on all
      substrates. These results suggest that the putative interfacial recognition
      domain of LCAT plays an important role in regulating the interaction of the
      enzyme with its organized lipoprotein substrates.

PMID- 10065714
TI  - Association and dissociation kinetics of bobwhite quail lysozyme with monoclonal
      antibody HyHEL-5.
AB  - The anti-hen egg lysozyme monoclonal antibody HyHEL-5 and its complexes with
      various species-variant and mutant lysozymes have been the subject of
      considerable experimental and theoretical investigation. The affinity of HyHEL-5
      for bobwhite quail lysozyme (BWQL) is over 1000-fold lower than its affinity for
      the original antigen, hen egg lysozyme (HEL). This difference is believed to
      arise almost entirely from the replacement in BWQL of the structural and
      energetic epitope residue Arg68 by lysine. In this study, the association and
      dissociation kinetics of BWQL with HyHEL-5 were investigated under a variety of
      conditions and compared with previous results for HEL. HyHEL-5-BWQL association
      follows a bimolecular mechanism and the dissociation of the antibody-antigen
      complex is a first-order process. Changes in ionic strength (from 27 to 500 mM)
      and pH (from 6.0 to 10.0) produced about a 2-fold change in the association and
      dissociation rates. The effect of viscosity modifiers on the association reaction
      was also studied. The large difference in the HEL and BWQL affinities for HyHEL-5
      is essentially due to differences in the dissociation rate constant.

PMID- 10065715
TI  - A comparison of collared and collarless femoral components in primary cemented
      total hip arthroplasty: a randomized clinical trial.
AB  - Between July 1986 and November 1989, 437 consecutive primary cemented total hip
      arthroplasties were performed using a straight-stemmed titanium alloy femoral
      component. Collared and collarless versions of this identical stem were randomly
      chosen by computer allowing a comparison between 213 collared stems (198
      patients) and 224 collarless stems (209 patients). Diagnosis, sex, weight, and
      average age (72.8 years, collared; 72.0 years, collarless) were similar. Follow
      up averaged 76 months (collared) and 72 months (collarless) with 49 patients
      followed for at least 10 years. Calcar-collar contact was noted in 205 hips (96%)
      on the initial postoperative radiograph. Early complications, including
      dislocations (5% each group), were similar. Late complications included 3 deep
      infections (2 collared, 1 collarless) and 2 postoperative femur fractures (1
      each). Hip scores at the most recent follow-up averaged 91.2 and 90.1 in the
      collared and collarless groups. No or slight pain was noted in 93% of collared
      and 91.5% of collarless hips. Although no radiographic differences were noted in
      distal cortical hypertrophy, stem subsidence, and osteolysis, collarless hips
      lost significantly more medial femoral neck cortical bone (average 0.90 mm vs
      0.63 mm). A higher incidence of radiolucent lines in femoral zone VI (20.7% vs
      9.4%) was also noted in collarless hips.

PMID- 10065716
TI  - Acetabular reconstruction in developmental dysplasia of the hip: results of the
      acetabular reinforcement ring with hook.
AB  - This study examined the clinical results and technical challenges associated with
      acetabular reconstruction in developmental dysplasia of the hip using the
      acetabular reinforcement ring with hook. We reviewed 33 consecutive
      reconstructions performed by a single surgeon. At an average follow-up of 6.7
      years, the mean Merle-d'Aubigne score had increased from 7 to 16. Two revisions
      were performed for aseptic loosening. Of the unrevised hips, 1 was classified as
      definitely loose and 1 as possibly loose. These results compare favorably with
      others in the literature. The acetabular reinforcement ring may prevent graft
      resorption and cup migration, major causes of socket failure in reconstruction of
      the deficient acetabulum.

PMID- 10065717
TI  - Polyethylene wear and synovitis in total hip arthroplasty: a sonographic study of
      48 hips.
AB  - Forty-six patients (48 hips), operated on with cemented total hip arthroplasty
      (THA) because of arthrosis, were examined radiographically and sonographically at
      10-year follow-up. Polyethylene wear of acetabular cups was measured on
      conventional non-weight-bearing pelvic radiographs, and the volume of
      polyethylene debris was calculated. Radiographic signs of loosening were
      identified. The capsular distance (ie, thickness of the synovium or synovial
      contents) was measured sonographically. We found a significant correlation
      between increased volumetric wear and increased capsular distance. Hips with
      radiographically loose acetabular components had significantly greater volumetric
      wear and capsular distance than those without signs of acetabular loosening. This
      relationship was not observed in hips with radiographically loose femoral
      components. In cemented THA, the volume of polyethylene wear debris and the
      thickness of the synovium and the synovial contents are related. In the event of
      radiographic loosening of the acetabular component, they are both increased.

PMID- 10065718
TI  - Major bone transplantation in total knee arthroplasty: a 2- to 9-year
      radiostereometric analysis of tibial implant stability.
AB  - Eight total knee arthroplasties involving major bone grafting to repair
      noncontained defects of the proximal tibia were studied. In all knees, autologous
      bone was used. Cement was used for implant fixation. At follow-up evaluation 5
      years after surgery, 7 knees had excellent results, and 1 had fair results; the
      mean Hospital for Special Surgery score was 84. Radiostereometric analysis showed
      a mean migration of 0.5 mm (range, 0.2-1.5 mm). None of the knees in which major
      structural autologous bone grafting was used showed increased micromotion of the
      adjacent tibial implant.

PMID- 10065719
TI  - Effect of stem stiffness and bone stiffness on bone remodeling in cemented total
      hip replacement.
AB  - The hypothesis in this study is that the stem stiffness-to-bone stiffness ratio
      influences the incidence and type of bone remodeling and fixation with cemented
      total hip arthroplasty. Ninety-one patients with 99 hips had cemented stems using
      3 different anatomic porous replacement designs. The APR I and APR II titanium
      stems with proximal porous coating on the proximal one fourth of the stem were
      cemented into 49 and 35 patients. The APR II-C stem, which is a cobalt-chrome
      stem only for cemented fixation, was cemented into 15 patients. These 3 different
      stem designs were used to study different metals as well as different stem
      shapes. The average follow-up was 4.3 years (range, 2-10 years) with all hips
      having 2 years' follow-up and 42 hips at least 5 years' follow-up. Bone
      remodeling was measured as stress shielding, calcar resorption, and distal
      hypertrophy on anteroposterior and lateral radiographs of the hip. Stress
      shielding was measured by the 4 grades described by Engh. A stem stiffness-to
      femoral bone stiffness ratio was calculated from the plain radiographs with the
      stem stiffness known from the manufacturer and the bone stiffness calculated
      using measurements of the outer and inner diameters of the femur. There was no
      statistical difference for bone remodeling and fixation between the 3 stem shapes
      or 2 metal types used in these hips. No stem was loose, and only 10 had
      radiolucent lines. Stress shielding was statistically related to stem stiffness
      but was more strongly related to the axial stiffness ratio, mediolateral bending
      stiffness ratio, anteroposterior stiffness ratio, and torsional stiffness ratio.
      Stress shielding grade 3 and 4 was present in 20% of hips with a torsional
      stiffness ratio < 0.33, in 38% of hips with a torsional stiffness ratio of 0.34
      to 0.5, and in 70% of hips with a torsional stiffness ratio > 0.5. Five-year
      results showed no statistical change in stress shielding, calcar resorption, and
      distal hypertrophy from the 2-year observations. The stem stiffness-to-bone
      stiffness ratio influenced bone remodeling but not fixation of these cemented
      stems.

PMID- 10065720
TI  - Results of a method of leg-length equalization for patients undergoing primary
      total hip replacement.
AB  - The postoperative leg-length discrepancy was determined radiographically for a
      consecutive series of 351 patients (408 hips) who underwent bilateral or
      unilateral primary total hip replacement using a single method of leg-length
      equalization by preoperative planning with overlay templates. The method of
      equalization was performed by a measurement of the femoral head and neck segment
      to be resected from a reference point at the superior aspect of the dislocated
      femoral head. The amount of femoral bone resected was determined preoperatively
      by determining the dimensions of the acetabular component thickness and the
      femoral component head and neck height that would be replacing this resected bone
      and adjusting this distance for any preexisting leg-length discrepancy. Using
      this leg-length equalization method, the length of the modular femoral head neck
      was chosen preoperatively, rather than using soft tissue tension across the
      prosthetic hip joint to determine whether the leg lengths were equal.
      Postoperative leg lengths were determined radiologically from a measurement from
      the acetabular teardrop to the lesser trochanter. Ninety-seven percent of the
      patients had a postoperative leg-length discrepancy that was less than 1 cm, and
      86% had a leg-length difference that was 6 mm (1/4 inch) or less. The average
      postoperative discrepancy for these 351 patients was 1 mm.

PMID- 10065721
TI  - Relationship between wear debris particles and polyethylene surface damage in
      primary total knee arthroplasty.
AB  - To study relationships between design and wear, particles were isolated from
      tissues around 75 failed primary total knee prostheses, and particle size and
      concentration were compared with the extent and distribution of wear on superior
      and inferior polyethylene surfaces of the corresponding implants. Twenty-four
      heat-pressed, posterior cruciate ligament (PCL)-retaining (group I: PCA knee), 19
      non-heat-pressed, PCL-retaining with relatively flat surfaces (group II: AMK,
      Kinematic, Microloc, Ortholoc), 14 non-heat-pressed, PCL-retaining with
      relatively congruent surfaces (group III: Townley Arizona), and 18 PCL-resected
      implants (group IV: Insall-Burstein, Total Condylar) were evaluated. Groups III
      and IV had fewer particles, smaller particles, and less surface damage than
      groups I and II. Implants with third-body wear had relatively small debris
      particles; those with thinner polyethylene had more severe surface delamination
      and more wear between liner and metal base. Groups I and II had more rotationally
      asymmetric wear patterns than groups III and IV. The size and concentration of
      debris particles might reflect, in part, different dominant wear mechanisms among
      implants of different designs.

PMID- 10065722
TI  - Correction of varus deformity with tibial flip autograft technique in total knee
      arthroplasty.
AB  - A simple method of autogenous bone grafting is described for correction of varus
      deformity during total knee arthroplasty. This technique uses a wedge of bone
      resected from the proximal tibia, which is flipped to augment the medial
      compartment. It is recommended in osteoarthritic knees with 15 degrees to 20
      degrees of varus angular deformity resulting from peripheral rim tibial defects
      involving the medial compartment. This method corrects varus deformity, preserves
      bone stock, and creates a stable platform for seating of tibial components
      without the need for internal fixation.

PMID- 10065723
TI  - Cementless fixation in 2-stage reimplantation for periprosthetic sepsis.
AB  - Twenty-five patients with documented infection of the hip were reviewed. All
      patients underwent reconstruction in a 2-stage fashion with cementless implants.
      The average follow-up in this group was 41 months. The average time to
      reimplantation was 4.8 months. Of the 25 living patients, 22 retained their
      implants. There were 2 recurrences of infection, for an infection recurrence rate
      of 8% (2 of 25). The average postoperative Harris Hip Score was 81. Bone ingrowth
      was confirmed radiographically via the Engh fixation score in all but 1 of the
      surviving implants. Cementless fixation in 2-stage reimplantation can result in
      acceptable eradication rates, while supplying predictable fixation, provided that
      appropriate cementless revision implants are used.

PMID- 10065724
TI  - The cost effectiveness of streamlined care pathways and product standardization
      in total knee arthroplasty.
AB  - The orthopaedic department at Providence Medical Center, Seattle, Washington,
      instituted a streamlined care pathway and product standardization for total knee
      arthroplasty (TKA) in July 1995. The goal was to reduce operating room time and
      to streamline the care pathway for a safe, expedited hospitalization of patients.
      The hospital staffs standardized nursing orders, cut the instrument systems from
      13 to 4 sets, and coordinated the expedited care pathway. Fifty-two consecutive
      primary TKAs were compared prepathway to 77 consecutive primary TKAs postpathway.
      The average length of stay declined 1.9 days from 5.1 to 3.2. The tourniquet time
      declined from 61 minutes to 56 minutes. The average dollar charges were $1,063
      less. There were no infections in either group. The manipulation rate for
      adhesions declined 37%.

PMID- 10065725
TI  - A rotating-hinge knee replacement for malignant tumors of the femur and tibia.
AB  - We evaluated the 2- to 7-year results of a rotating-hinge knee replacement after
      excision of malignant tumors of the knee joint. There were 25 distal femoral and
      7 proximal tibial replacements. The 5-year prosthetic survival for distal femoral
      replacements was 88%, compared with 58% for proximal tibial replacements. Seven
      patients underwent prosthetic exchange: 1 for aseptic loosening, 2 for wound
      slough and perioperative infection, and 4 for articulating component failure. One
      patient underwent above-knee amputation owing to skin necrosis. The median
      functional scores at the latest follow-up were 27 by the International Society of
      Limb Salvage evaluation system and 80 by the Hospital for Special Surgery Knee
      Score system. This implant is a promising choice for joint reconstruction after
      excision of tumors at the knee joint.

PMID- 10065726
TI  - The effect of a tourniquet on intraoperative patellofemoral tracking during total
      knee arthroplasty.
AB  - A prospective investigation was performed on the effect of the tourniquet on
      intraoperative patellofemoral tracking during primary total knee arthroplasty
      (TKA). A total of 75 TKAs in 67 patients were performed by 1 surgeon in a
      consecutive series using the same technique. Using strict criteria, patellar
      tracking was assessed both before and after tourniquet release. Patients were
      placed into 1 of 3 groups: Group I were knees that tracked properly both before
      and after tourniquet release. Group II were knees that maltracked with the
      tourniquet inflated and subsequently corrected with the tourniquet released.
      Group III were knees that maltracked both before and after tourniquet release,
      therefore requiring a lateral release. Knees were categorized as group I, 34 of
      75 (45.3%); group II, 36 of 75 (48.0%); and group III, 5 of 75 (6.7%). Using this
      criterion, lateral release was avoided in all group II knees. Tourniquet
      application alters intraoperative patellofemoral tracking during TKA. When
      contemplating lateral release, tourniquet deflation and reevaluation of
      patellofemoral tracking should be considered.

PMID- 10065727
TI  - Degenerative changes in normal femoral heads in the elderly.
AB  - Unipolar hemiarthroplasty and bipolar hemiarthroplasty are frequently chosen for
      treating subcapital hip fracture; however, clinical outcome varies substantially.
      Although total hip arthroplasty is indicated for subcapital hip fracture in
      patients with degenerative hip disease, there is a lack of data on the incidence
      and extent of degenerative change in patients with subcapital hip fracture
      without obvious degenerative hip disease. This investigation evaluated articular
      cartilage in 25 consecutive femoral heads removed from elderly patients who
      sustained acute femoral neck fracture. All patients' femoral heads demonstrated
      grade 2 or 3 chondromalacia with an average involvement of 54% of the whole
      femoral head surface area. Review of the literature describes the cost-to-benefit
      ratio associated with painful hip arthroplasty. This study demonstrated a high
      incidence of femoral head degenerative change, which may account for the variable
      clinical results and proliferation of the term unsolved fracture. In the patient
      with a subcapital hip fracture, total hip arthroplasty may prove to be a better
      alternative.

PMID- 10065728
TI  - Extensor apparatus reconstruction with Leeds-Keio ligament in total knee
      arthroplasty.
AB  - The outcome of reconstruction of patellar tendon rupture in total knee
      arthroplasty has not been particularly good. Five cases of extensor mechanism
      rupture in total knee arthroplasty are presented. The surgical technique
      consisted of suture of the extensor apparatus augmented by a Leeds-Keio ligament.
      Active extension of -10 degrees was achieved by all the patients with flexion of
      90 degrees or more. One superficial infection developed, which required
      antibiotic treatment. In the course of time, the reconstruction elongated less
      than 1 cm without significantly affecting function. Although the numbers are
      small and the complications significant, the final results of this technique have
      been reasonable. The technique permits early weight bearing and immediate
      mobilization, which enables an adequate range of motion to be achieved.

PMID- 10065729
TI  - The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone
      cements.
AB  - An in vitro study was carried out comparing the elution characteristics of
      Palacos-R and CMW acrylic cements. Three groups of 6 antibiotic-loaded cement
      disks were prepared, incorporating 1.0 g vancomycin and 2.4 g tobramycin per 40 g
      packet of cement. Palacos-R bone cement was used for group 1, CMW 1 for group 2,
      and CMW 3 for group 3. The disks were placed in saline baths for 9 weeks. The
      baths were periodically sampled and elution rates calculated. CMW 1 released 24%
      less tobramycin and 36% less vancomycin than Palacos-R over the total study
      period (P < .05). CMW 3 released 34% less tobramycin and 38% less vancomycin than
      Palacos-R (P < .05). There was no significant difference in antibiotic release
      between CMW 1 and CMW 3. The in vitro elution characteristics of Palacos-R are
      superior to CMW.

PMID- 10065730
TI  - In vitro stress shielding measurements can be affected by large errors.
AB  - Hip prostheses and other implantable devices for the proximal femur are tested
      experimentally to study their effects on load transfer. We report on some
      experimental errors (related to the load simulation) that can undermine the
      reliability of strain measurements. A first source of error is that of
      overconstraining the setup. This situation makes it impossible to control or even
      determine the force values. The second source of error is related to geometric
      alterations induced by surgery, which modify the lever arms and thus the loading
      system. Two options are available to compensate for a geometric alteration:
      either applying the same system of forces or the same resultant bending moment to
      the implanted femur. The errors that arise if these parameters are not controlled
      can make it impossible to determine if one device performs better or worse than
      another.

PMID- 10065731
TI  - Femoral bone blood flow after reaming and intramedullary canal preparation: a
      canine study using laser Doppler flowmetry.
AB  - This study was conducted to determine the effect of intramedullary reaming and
      canal preparation on bone blood flow in the proximal femur. Thirty-five adult
      dogs were randomly assigned to have their intramedullary canals prepared after
      reaming in the following manner: group 1, ream only; group 2, lavage; group 3,
      methylmethacrylate cement introduction; group 4, cement pressurization after
      placing a cement restrictor; group 5, lavage then cement introduction; and group
      6, lavage then cement pressurization. Bone blood flow was measured at both
      metaphyseal and diaphyseal sites by using laser Doppler flowmetry before reaming,
      after reaming, after lavage, after cementing, and at 6 weeks after the procedure
      just before euthanasia. Reaming significantly decreased bone blood flow in the
      diaphysis (P = .046) but not in the metaphysis. Cement introduction and cement
      pressurization both significantly decreased bone blood flow in the metaphysis (P
      = .035, P = .004) and diaphysis (P = .007, P = .029). Pressurization of cement
      had a significantly greater relative effect than cement introduction alone in the
      diaphysis (P = .006) but not in the metaphysis. Lavage had no effect on bone
      perfusion. Bone blood flow was significantly increased at 6 weeks after the
      initial procedure in both the metaphysis (P = .049) and the diaphysis (P = .004).
      The results suggest that reaming decreases diaphyseal cortical but not
      metaphyseal bone blood flow significantly, whereas lavage has no effect. Cement
      introduction with or without pressurization has a significant detrimental effect
      on metaphyseal and diaphyseal blood flow. These findings have implications for
      intramedullary nailing and for canal preparation when performing arthroplasty.

PMID- 10065732
TI  - Analysis of lower extremity embolic material after total knee arthroplasty in a
      canine model.
AB  - Emboli assumed to consist of fat, marrow, cement, and bone are generated during
      total knee arthroplasty. This study collected and identified the constituents of
      the embolic debris and assessed the effects of intramedullary cutting guides in a
      canine model. During cemented knee arthroplasties with or without the use of
      intramedullary guides, all embolic debris was collected in a single lobe of lung.
      In dogs using intramedullary guides, transesophageal echocardiography revealed a
      sustained embolic shower, and histologically marked amounts of emboli obstructed
      the pulmonary vasculature. The emboli were composed of fat cells and
      hematopoietic cells (marrow elements) interspersed with free fat globules. Marrow
      elements are the primary constituents of the emboli generated during total knee
      arthroplasty. Intramedullary guides increased debris generation.

PMID- 10065733
TI  - A simple technique for handling morcellized bone-graft during impaction grafting.
AB  - Handling morcellized bone-graft during impaction grafting can be a slow and
      laborious procedure. An alternative quick technique is described.

PMID- 10065734
TI  - Safe removal of massive intrapelvic cement using ultrasonic instruments.
AB  - The extraction of massive intrapelvic deposits of cement in revision total hip
      arthroplasty presents the surgeon with a philosophical dilemma and a technical
      challenge. The cement is difficult to remove because of the disparity between the
      size of the cement mass and the defect in the acetabulum. In addition, the cement
      mass lies close to major intrapelvic organs, and the use of force applied with
      sharp cement-removing instruments poses a danger to these structures. We report
      on the ultrasonic technique of cement removal used to extract a massive
      intrapelvic cement deposit safely.

PMID- 10065735
TI  - Disseminated intravascular coagulation in elective primary total hip replacement.
AB  - Acute disseminated intravascular coagulation is a common and potentially serious
      complication of many clinical conditions, including trauma. We report two cases
      in which this condition occurred after routine elective primary total hip
      replacement.

PMID- 10065736
TI  - Immunoglobulin variable regions usage by B-lymphocytes infiltrating a human
      breast medullary carcinoma.
AB  - Breast medullary carcinoma are heavily infiltrated by B-lymphocytes and
      associated with a good prognosis despite their high histological grade. We
      investigated the Ig repertoire of B-lymphocytes infiltrating one such tumour. A
      single cell suspension was obtained from a tumor specimen by enzymatic digestion.
      VH, Vkappa, and Vlambda regions were amplified by RT-PCR using mixtures of
      primers optimized to maximize the diversity of the PCR products. They were then
      cloned and sequenced. Analysis of 9 VH, 5 Vkappa, and 10 Vlambda sequences using
      the Kabat database indicated that several VH and VL region subgroups (I, II and
      III) are expressed by B-lymphocytes infiltrating this tumor. The analysis of CDR3
      regions also showed a variability, although some VH and VL clones exhibited
      identical or nearly identical sequences. Thus, the B-cell infiltration observed
      in this breast medullary carcinoma does not reflect a monoclonal proliferation
      and represents an oligoclonal or a polyclonal B-cell proliferation.

PMID- 10065737
TI  - bcl2 and v-abl oncogenes cooperate to immortalize murine B cells that secrete
      antigen specific antibodies.
AB  - In this manuscript, a general strategy was designed and used to rapidly test
      whether any combination(s) of p53, v-abl, bcl2 and ras oncogenes could act
      cooperatively to immortalize B cells. Here we report that only the combination of
      v-abl and bcl2 was successful. Splenic B cells from beta galactosidase-immunized
      mice were stimulated in vitro with lipopolysaccharide and dextran sulphate for 48
      h and co-infected with ecotropic A-MuLV (v-abl) and amphotropic pZip-bcl2 (human
      bcl2) viruses. When inoculated i.p. into naive pristane-primed mice, these B
      cells generated mesenteric lymphadenopathy, intraperitoneal lymph nodules and
      ascites in 100% (8/8) of the mice within 36-53 days. The ascites fluid contained
      69.5-122 microg/ml IgG and 2.5-13 microg/ml IgM against the immunogen. The
      ascites cells were passed intraperitoneally up to three times. In all passages,
      ascites tumors were generated, and the ascites fluid contained beta galactosidase
      specific IgG and IgM, indicating that some immunoglobulin secreting B cells had
      been immortalized. Neither ascites nor tumors were produced when B cells infected
      with only one of the viruses was injected into the mice. The presence of each
      oncogene in ascites cells was verified by immunohistochemistry or RT-PCR. This
      study provides evidence for the cooperativity of an unexpected pair of oncogenes
      in B cell immortalization.

PMID- 10065738
TI  - IL-4-dependent IgE class switching in an anti-trinitrophenyl B-cell hybridoma
      after engagement of antigen receptors.
AB  - A B-cell hybridoma, TP67.21 that expresses surface anti-trinitrophenyl (TNP) IgM
      but does not secrete the antibody spontaneously has been reported to
      differentiate into anti-TNP IgM-secreting cells in response to lipopolysaccharide
      or engagement of surface IgM. Here, we report isolation and characterization of a
      subclone, TP67.21E (TP.E) that undergoes isotype switching to IgE in an
      interleukin (IL)-4-dependent manner. TP.E cells secreted anti-TNP IgE depending
      on exogenous IL-4 when they were cultured with an anti-IgM antibody for 6-8 days.
      8-Mercaptoguanosine, which has been shown to enhance IgE class switching in
      murine splenic B-cells further augmented the IgE response in TP.E cells.
      Immunofluorescence microscopy revealed that approximately 1.2% of the cultured
      cells became positive for intracellular IgE after the stimulation culture. The
      germline epsilon transcripts were expressed transiently on days 2-4 of the
      culture, while expression of the productive epsilon transcripts was induced 5
      days after the start of the culture, thus suggesting that IgE class switching
      occurred in TP.E cells under these conditions.

PMID- 10065739
TI  - Dietary omega-3 polyunsaturated fatty acids from fish oil reduce interleukin-12
      and interferon-gamma production in mice.
AB  - The objective of this study was to investigate the impact of feeding mice a diet
      rich in n-3 polyunsaturated fatty acids (PUFA) from fish oil on the interleukin
      12 (IL-12) and interferon-gamma (IFNgamma) production during the early stage of
      an infectious challenge with Listeria monocytogenes. Weanling female C3H/HeN mice
      were fed AIN-93G experimental diets containing 20%, by weight one of three fat
      sources: lard (low PUFA), soybean oil (n-6 PUFA) or a mixture (9:1) of menhaden
      fish oil and corn oil (n-3 PUFA). After 4 weeks, mice were injected
      intraperitoneally with 10(5) Listeria monocytogenes and the concentration of IL
      12(p70) and IFNgamma in serum was determined 24 h post-infection by ELISA. IL
      12p35, IL-12p40 mRNA, and IFNgamma mRNA in the spleen were quantified by RNase
      protection assay. The number of IFNgamma-producing cells in the spleen was
      determined by flow cytometry using an intracellular staining procedure. We found
      that n-3 PUFA-fed mice had lower levels of circulating IL-12 at 24 h post
      infection than n-6 PUFA- or low PUFA-fed mice (9.7+/-3.4 pg/ml vs. 61.6+/-10.6,
      and 44.4+/-12.5 pg/ml, respectively; P=0.002, n = 10/trt). The level of IL-12 p35
      mRNA did not significantly differ among dietary treatment groups. However, IL
      12p40 mRNA was significantly lower in n-3 PUFA- and n-6 PUFA-fed mice compared to
      low-PUFA-fed mice. Further, the n-3 PUFA group also had the lowest circulating
      IFNgamma (4.4+/-1.8 ng/ml vs. 9.1+/-1.0, and 9.7+/-2.1 ng/ml, respectively; P =
      0.007. n = 8-10/trt). The n-3 PUFA-fed mice had significantly lower IFNgamma mRNA
      in their spleens compared to the mice fed the other fat sources. In agreement
      with having lower circulating IFNgamma and lower splenic IFNgamma mRNA, n-3 PUFA
      fed mice had a significantly lower percentage of IFNgamma-producing cells in
      their spleens compared with the n-6 PUFA-fed group (2.1+/-0.6 vs. 4.2+/-0.7%; P =
      0.037, n = 10/trt). In summary, feeding mice a diet rich in n-3 PUFA from fish
      oil significantly lowered the production of both IL-12 and IFNgamma during the
      early phase of a Listeria infection.

PMID- 10065740
TI  - Therapeutic and prophylactic uses of protein A in the control of Leishmania
      donovani infection in experimental animals.
AB  - The role of the immunomodulator Protein A (PA) (from Staphylococcus aureus, Cowan
      I strain) in the control of leishmanial infection was studied in experimental
      animals. Treatment of Leishmania donovani infected hamsters with PA led to a
      moderate level of reduction of parasite load in their spleen (68%) and liver
      (46%). However, combination therapy of PA with the antileishmanial drug stibanate
      induced a more marked reduction of the spleen (88%) and liver (85%) parasitemia
      compared to that induced by PA or drug treatment alone. Similar results were also
      obtained with L. donovani infected BALB/c mice as the combination therapy of PA
      and stibanate led to a significant reduction (84%) of liver parasite load in
      comparison to that induced by PA (38%) or drug (61%) treatment alone. Apart from
      its therapeutic use, PA could also be used as a prophylactic agent in the control
      of leishmanial infection. Thus, treatment of hamsters with PA before leishmanial
      challenge significantly reduced their organ parasite load (by 59-78%) compared to
      that observed in infected controls without prior PA treatment. The
      antileishmanial effect of PA was likely to be mediated through the activation of
      macrophages leading to an enhancement of their phagocytic as well as
      leishmaniacidal activities. Subsequent studies demonstrated that PA treatment led
      to an increased production of nitric oxide by macrophages which could primarily
      be responsible for their enhanced parasite killing ability.

PMID- 10065741
TI  - Autocrine B-cell stimulation by interleukin-2 during a cognate interaction with T
      cells.
AB  - Interleukin-2 (IL-2) secretion as well as expression of IL-2 receptor has been
      demonstrated for B-cells in response to several activating stimuli. However, the
      exact role of B-cell-derived IL-2 in the T-cell-dependent antibody response
      remains to be determined. Here, we have examined the autocrine regulatory roles
      of IL-2 secreted from B-cells. Splenic resting B-cells were stimulated with a
      fixed pre-activated Th1 clone, G1.19, in the presence of a single amino acid
      substituted peptide (pD129A; Ala-129 substituted for Asp-129), an analog of the
      original ligand (p119-133, derived from bovine beta-lactoglobulin) recognized by
      G1.19 cells. pD129A allowed a cognate interaction between B-cells and fixed pre
      activated G1.19 T-cells, but pD129A had no agonistic activity against G1.19 T
      cells. Thus, the level of expression of B-cell-activating molecules on T-cells
      remained unchanged after stimulation with pD129A. Regardless of the lack of
      ability to induce IL-2 secretion in the case of T-cells, pD129A significantly
      enhanced antibody secretion from B-cells, and this was partially blocked by anti
      IL-2 antibody. Furthermore, IL-2 secretion from B-cells was modestly upregulated
      in response to added pD129A. Taken together, these data suggest that helper
      signals from interacting cognate T-cells induce IL-2 secretion by B-cells, which
      can enhance antibody secretion in an autocrine manner.

PMID- 10065742
TI  - Involvement of protein kinases in signalling for nitric oxide (NO) and tumour
      necrosis factor alpha (TNF) production by monocytes stimulated with colorectal
      DeTa cancer cells: the lack of evidence for the role of TNF in the regulation of
      NO production.
AB  - Kinases that are involved in NO and TNF production by human monocytes (MO)
      stimulated by colorectal cancer (DeTa) cells and effects of exogenous and
      endogenously synthesized TNF on NO induction were studied. The results based on
      the use of various inhibitors of protein kinases suggest that different
      signalling pathways operate in MO during induction of TNF and NO release after
      stimulation by DeTa cells. Stimulation of NO production required at least PTK,
      PKC and PKA, but only PTK and PKC were engaged in signal transduction for TNF
      production. Exogenous TNF and TNF produced by MO upon contact with DeTa cells was
      not sufficient for the induction or enhancement of NO synthesis in MO. The TNF
      synthesis was not influenced by neither exogenous nor endogenous NO produced by
      MO in the co-culture. Therefore, signal transduction pathways operating in MO
      during NO induction seem to be different from these engaged in TNF production,
      and both regulatory pathways probably operate in MO independently.

PMID- 10065743
TI  - CD80 and CD86 costimulatory molecules on circulating T cells of HIV infected
      individuals.
AB  - The expression of CD80 and CD86 costimulatory molecules, typical for antigen
      presenting cells (APC), was measured on circulating T cells of 20 HIV-infected
      individuals and of 11 HIV-negative healthy controls. The CD80 and CD86 molecules
      were present on both circulating T subsets of HIV-infected individuals (mean of
      CD80 expression within CD4+ T cells [CD80/CD4]: 5.0%; and CD86/CD4: 2.6%;
      CD80/CD8 4.1% and CD86/CD8: 2.7%) and were associated with HLA-DR expression.
      Some CD80 and CD86 expression was also found in normal controls, and only the
      expression of CD86 was significantly (P < 0.05) increased on CD4 + and CD8 + T
      cells of HIV-infected individuals. The expression of CD28 was decreased on T
      cells of HIV-infected individuals and was negatively correlated to the expression
      of HLA-DR and CD86 (mean CD28 within CD3+T cells: HIV+ 29.5%, HIV - 67.6%;
      correlation coefficient, - 0.75 and - 0.71, respectively). The more the disease
      proceeds, the less CD28 and the more DR and CD86 are found on circulating T
      cells. This suggests that during HIV infection T cells themselves develop an
      antigen presenting phenotype by upregulating expression of HLA-DR, CD86 and CD80
      molecules.

PMID- 10065744
TI  - Identification of a coelomic mitogenic factor in Eisenia foetida earthworm.
AB  - Coelomic fluid of earthworms Eisenia foetida (Oligochaeta, Annelida) exerts a
      mitogenic activity on murine splenocytes. Total coelomic fluid was subjected to
      size-exclusion chromatography and a semi-purified mitogenic fraction (fraction 5)
      was isolated and further characterized. Both coelomic fluid and the semi-purified
      fraction 5 block concanavalin A (ConA)-induced spleen cell proliferation but
      exert a synergistic effect on LPS-triggered spleen cell proliferation. Using a
      polyclonal antiserum neutralizing the mitogenic activity of the semi-purified
      fraction 5, a 60-kDa component was identified and named CMF (coelomic mitogenic
      factor). CMF was found to bind ConA which could account for its ability to
      inhibit ConA-induced spleen cell proliferation. CMF is present in the coelomic
      fluid as a trimer of a 20-kDa protein. N-terminal amino acid sequence of
      monomeric CMF reveals partial sequence homology with phospholipase A2 (PLA2).
      Moreover, CMF-enriched coelomic fluid fraction 5 exerts phospholipase activity
      comparable with that of bovine pancreatic PLA2. Our results suggest that coelomic
      fluid of E. foetida contains a ubiquitous PLA2-like enzyme which might be
      involved in immune reactions in earthworms such as anti-bacterial mechanisms.

PMID- 10065745
TI  - The applied neuropathology of human spinal cord injury.

PMID- 10065746
TI  - Treatment of infertility.

PMID- 10065747
TI  - Changes in lipid, lipoprotein and apolipoprotein profiles in persons with spinal
      cord injuries during the first 2 years post-injury.
AB  - OBJECTIVE: To investigate changes in lipid, lipoprotein and apolipoprotein
      profiles in persons with spinal cord injury (SCI) during the first 2 years post
      injury, and to determine whether changes in risk profiles were associated with
      sport activity and/or changes in physical capacity parameters. DESIGN: Risk
      profiles and physical capacity were investigated in 19 subjects with recent SCI
      during rehabilitation (t1) and +/- 1 year after discharge from rehabilitation
      (t2). MAIN OUTCOME MEASURES: Changes in total plasma cholesterol (TC), high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C), triglycerides (TG), apolipoprotein-A1 (ApoA1), apolipoprotein-B (ApoB)
      concentrations, the ratios TC/HDL-C, LDL-C/HDL-C, ApoA1/ApoB and HDL-C/ApoA1, and
      physical capacity (maximal isometric strength, sprint power output, maximal power
      output, aerobic power). RESULTS: Risk profile parameters changed towards more
      favorable values at t2, except for HDL-C (P=0.06), TG and HDL-C/ApoA1. Sport
      activity and changes of the physical capacity were the most important
      determinants of changes in lipid and (apo)lipoprotein profiles, showing more
      favorable values with larger increases of the physical capacity and in persons
      who were physically active. CONCLUSION: Results show that the lipid and
      (apo)lipoprotein profiles improve in persons with SCI during the first 2 years
      post-injury, and that improving the physical capacity or being physically active
      can improve the lipid and (apo)lipoprotein profiles.

PMID- 10065748
TI  - Extradural infections of the spine.
AB  - OBJECTIVES: We have observed a recent increase in the incidence of spinal
      extradural infections. To determine postoperative outcome and prognosis we have
      undertaken a retrospective study on patients with spinal extradural abscesses
      between 1978 and 1996 treated in the Department of Neurosurgery at the Nordstadt
      Hospital in Hannover, Germany. METHODS: Case records, outpatient files, operation
      notes, neuroradiological examinations and pathological reports were analysed.
      Neurological function was documented using a score system for each symptom.
      RESULTS: Twenty-two patients underwent 24 operations during the study period.
      Staphylococcus aureus was the organism most commonly isolated. Patients presented
      after a mean history of 1.8+/-2.6 months with acute development of severe para-
      or tetraparesis and were followed up for an average period of 6+/-7 months. Two
      groups were distinguished. One group was characterized by epidural collections of
      pus (14 patients). Two patients in this group were not operated due to their
      moribund state and died from uncontrollable septicemia. Two of the remaining 12
      operated patients died within 30 days after surgery due to generalized septicemia
      or other medical problems unrelated to the spinal involvement. Of the ten
      surviving patients, five sustained major neurological deficits, whereas the
      remaining five patients made an incomplete recovery. The second group consisted
      of eight patients in a significantly better pre-operative health condition in
      whom granulomatous material was obtained during the operation and the outcome was
      considerably better. No patient in this group died. Six patients recovered with
      no or mild neurological deficits. CONCLUSION: Spinal extradural infections
      require immediate surgical intervention. Neurological outcome depends on the pre
      operative neurological status. Survival is determined by the general health
      condition of the patient.

PMID- 10065749
TI  - A two-part pilot study of sildenafil (VIAGRA) in men with erectile dysfunction
      caused by spinal cord injury.
AB  - STUDY DESIGN: This was a two-part pilot study in men with erectile dysfunction
      (ED) due to spinal cord injury (SCI: cord level range T6-L5). Part I was a
      randomised, double-blind, two-way cross-over study comparing a single dose of
      sildenafil 50 mg or placebo. Part II was a randomised, double-blind, parallel
      group evaluation of sildenafil 50 mg or placebo, taken as required (not more than
      once daily) approximately 1 h prior to sexual activity, over a period of 28 days.
      OBJECTIVES: To assay the efficacy and safety of sildenafil 50 mg and placebo.
      SETTING: Clinic- and home-based assessments in the United Kingdom. METHODS: A
      total of 27 subjects who were able to achieve at least a grade 2 erection (hard,
      but not hard enough for penetration) in response to penile vibratory stimulation
      (PVS) were recruited. In Part I, the reflexogenic response of the penis to PVS
      was evaluated in the clinic while in Part II, the response to treatment was
      assessed in the home (global efficacy. questionniare, diary). RESULTS: In Part I,
      17/26 (65%) subjects had erections of >60% rigidity at the penile base (median
      duration 3.5 min) after sildenafil compared with 2/26 (8%) (median duration 0
      min) alter placebo (P=0.0003). In Part II, 9/12 (75%) subjects on sildenafil and
      1/14 (7%) subjects on placebo reported that the treatment had improved their
      erections (P<0.005), and 8/12 (67%) and 2/13 (15%) men, respectively, indicated
      that they wished to continue treatment (P<0.02). An analysis of diary data showed
      no difference between the groups with respect to the mean number of erections
      hard enough for penetration (P = 0.08). The mean proportion of attempts at sexual
      intercourse that were successful was 30 and 15%, respectively (P=0.21).
      Similarly, responses to the end-of-treatment questionnaire indicated that there
      were no significant differences between the groups with respect to the frequency
      of erections hard enough for sexual intercourse (P=0.47) or that lasted as long
      as the subject would have liked (P=0.11). No subject discontinued sildenafil due
      to adverse events. CONCLUSION: Sildenafil is an effective, well-tolerated oral
      treatment for ED in SCI subjects.

PMID- 10065750
TI  - Delayed diaphragm recovery in 12 patients after high cervical spinal cord injury.
      A retrospective review of the diaphragm status of 107 patients ventilated after
      acute spinal cord injury.
AB  - STUDY DESIGN: The functional outcome of the diaphragm after acute spinal cord
      injury was reviewed over a 16 year period for 107 patients who had required
      assisted ventilation in the acute phase. OBJECTIVES: To quantify the incidence of
      recovery of diaphragm function which occurred beyond the period of acute oedema;
      to produce a time-related profile of this as a guide to clinicians considering
      phrenic nerve pacing; and to assess the value of phrenic nerve testing in
      predicting recovery. SETTING: The Southport Regional Spinal Injuries Centre,
      Southport, England. METHODS: Bilateral phrenic nerve and diaphragm integrity was
      assessed clinically, by spirometry, and by fluoroscopy without and with phrenic
      nerve stimulation. RESULTS: Thirty-one per cent of all the ventilated patients
      (33 cases), with a level of injury between C1 and C4 (Scale A in ASIA Impairment
      Scale), had diaphragmatic paralysis at the time of respiratory failure. The
      subsequent diaphragm recovery which appeared in seven of these patients, between
      40 and 393 days (mean 143), permitted weaning from ventilatory support at 93 to
      430 days (mean 246) after the acute injury, with a vital capacity of over 15 ml
      kg(-1) at that stage. The diaphragm recovery in a further five patients, whose
      vital capacity remained below 10 ml kg(-1) and who could not be fully weaned,
      occurred significantly later, between 84 and 569 days (mean 290), P=0.053.
      Negative phrenic nerve tests were followed by weaning at a later interval in
      several cases. By contrast, one patient with an early positive phrenic
      stimulation test and subsequent diaphragm activity could not be weaned from the
      ventilator. CONCLUSION: Twenty-one per cent of the patients with initial
      diaphragm paralysis were ultimately able to breathe independently after 4 and 14
      months, whilst a further 15% had some diaphragm recovery. Phrenic nerve testing
      should be repeated at 3 monthly intervals for the first year after high
      tetraplegia.

PMID- 10065751
TI  - The QA pressure measurement system: an accuracy and reliability study.
AB  - OBJECTIVE: The main purpose of this study was to determine the accuracy and
      reliability of the Queen Alexandra Pressure Measurement System (QA PMS).
      Furthermore, we examined whether there were significant differences in measured
      pressures of the buttock area during sitting between normal subjects and spinal
      cord injured (SCI) patients. DESIGN: Accuracy (calibration) and reliability (test
      retest) study. SETTING: The spinal cord unit of Tertiary Care Centre 'De
      Hoogstraat' in Utrecht, The Netherlands. PATIENTS: A convenience sample of 16 SCI
      patients and 15 normal subjects. MAIN OUTCOME MEASURES: The accuracy was
      determined by using the Standard Error of the Mean (SEM, in mmHg). The Technical
      Error of Measurement (TEM, in mmHg) was calculated as measure for differences
      between two paired measurements. The reliability was determined by using an
      Intraclass Correlation Coefficient (ICC). Significant differences in measured
      pressures between both groups (P<0.05) were determined by using an unpaired (two
      sample) t-test. RESULTS: Accuracy (calibration): mean SEM=0.30 (+/-0.1) mmHg,
      indicating a high level of accuracy. Differences between two paired measurements:
      mean TEM calibration= 1.87 (+/-0.76) mmHg; mean TEM normal subjects=4.76 (+/
      1.78) mmHg; mean TEM SCI patients=6.34 (+/-2.19) mmHg. Reliability: mean ICC(3,1)
      calibration=0.85 (95% CI=0.74 0.95); mean ICC(2.1) normal subjects=0.92 (95%
      CI=0.90 0.94); mean ICC(2.1) SCI patients=0.90 (95% CI=0.88 0.92). The normal
      subjects had significantly higher mean pressures (P=0.028) than the SCI patients
      (mean pressures 31.0 vs 28.5 mmHg), whilst the SCI patients had significantly
      higher peak-pressures (P=0.0000) than the normal subjects (mean peak-pressures:
      134.1 vs 75.7 mmHg). CONCLUSIONS: The QA Pressure Measurement System has
      sufficient accuracy and good reliability as a measurement procedure. There are
      significant differences between the measured pressures of both groups: the
      significantly higher peak pressures of the SCI patients seem to be the most
      important.

PMID- 10065752
TI  - Reproducibility of the Adapted Leger and Boucher Test for wheelchair-dependent
      athletes.
AB  - STUDY DESIGN: This study analyzed the reproducibility of a field test. In a
      previous study, we showed that this test, the Adapted Leger and Boucher Test
      (ALBT), was progressive and maximal. The Leger and Boucher predictive equation
      for able-bodied subjects was not accurate for WD athletes, however, and a new
      predictive equation is needed. OBJECTIVES: To determine the reproducibility of an
      adapted incremental field test for wheelchair-dependent (WD) athletes. SETTING:
      France at Montpellier. METHODS: The proposed protocol was conducted on a 400 m
      track. Eight male paraplegics (mean age: 30.8+/-5.1 years) performed the test
      three times in the same conditions, ie same time of day, same wheelchair, same
      material. Maximal heart rate (HRmax) and maximal speed (Smax) were measured.
      RESULTS: We found no significant differences (P>0.05) between tests for either
      variable. The Bland and Altman graphic analyses showed a good reproducibility for
      both variables. Lastly, the reproducibility coefficients of HRmax and Smax were
      very low (2% and 1%, respectively). CONCLUSION: The ALBT is reproducible
      concerning measurements of HRmax and Smax. A valid predictive equation of maximal
      oxygen uptake from the Smax is now needed for WD athletes during this field test.

PMID- 10065753
TI  - The needs assessment checklist: a clinical approach to measuring outcome.
AB  - OBJECTIVE: To evaluate the outcome of the Needs Assessment and Goal Planning
      Programme used in the rehabilitation of people with spinal cord injuries. The
      Needs Assessment Programme incorporates a behavioural indicator rating scale to
      detail the individual's progress and rehabilitation needs. This can also be used
      to evaluate the outcome of the rehabilitation programme in general. The Needs
      Assessment Checklist (NAC) forms part of the programme and is a tool which is
      used to evaluate rehabilitation outcome. SETTING: A purpose built, national
      spinal injuries centre in the United Kingdom. SUBJECTS: 82 patients who had
      completed the Needs Assessment Checklist, both at the beginning and towards the
      end of the rehabilitative process. RESULTS: Independence, as measured by the
      Checklist, was significantly greater in all domains at the time of the second
      Needs Assessment. CONCLUSIONS: The Needs Assessment and Goal Planning Programme
      is successful in establishing greater client independence, whether assessed at a
      verbal or physical level. Team members have used the Needs Assessment Checklist
      as a behavioural indicator of rehabilitation outcome based on available standards
      of rehabilitative care. Further development of the Needs Assessment Checklist now
      needs to focus on establishing concurrent validity and test/retest reliability.
      The measure developed proved to be a useful, clinically relevant and patient
      friendly assessment of rehabilitation outcome.

PMID- 10065754
TI  - Pressure ulcer in a man with tetraplegia and a poorly fitting wheelchair: a case
      report with clinical and policy implications.

PMID- 10065755
TI  - Parenchymatous cerebral neurocysticercosis in a quadriplegic patient.
AB  - OBJECTIVE: To present and discuss a case of cerebral neurocysticercosis in a
      quadriplegic patient. DESIGN: Case report of a case of neurocysticercosis in a
      high level spinal cord injury (SCI) patient who developed episodes of autonomic
      dysreflexia and orthostatic hypotension associated with transient neurologic
      deficits and seizures. SETTING: Spinal Cord Unit of the University Hospital of
      Geneva, Switzerland. SUBJECT: Single patient case report. MAIN OUTCOME MEASURE:
      Clinical and radiological magnetic resonance imaging follow-up of the patient
      between July 1995 and October 1997. RESULTS: Treatment of cysticercosis with
      praziquantel relieved the patient from autonomic dysreflexia, symptomatic
      orthostatic hypotension, transitory neurological deficits and seizures.
      CONCLUSION: Diagnosis of neurocysticercosis in a quadriplegic patient might be
      difficult because of frequent overlaps with some usual symptoms occurring in high
      level SCI, mostly autonomic dysreflexia and orthostatic hypotension.
      Neurocysticercosis should be kept in mind when a SCI patient living in, or coming
      from endemic zones presents with new neurological abnormalities and seizures.
      Magnetic resonance imaging appears to be more sensitive than computerised
      tomography to confirm the diagnosis of active cysticercosis. Treatment with
      praziquantel associated with cimetidine to increase the drug bioavailability and
      prednisone to reduce the inflammatory reaction gives good results.

PMID- 10065756
TI  - Syncope following intramuscular injection of hydroxocobalamin in a paraplegic
      patient: indication for oral administration of cyanocobalamin in spinal cord
      injury patients.

PMID- 10065757
TI  - Interleukin-4 and interferon-gamma inhibit prostaglandin production by
      interleukin-1beta-stimulated human periodontal ligament fibroblasts.
AB  - The purpose of the present study was to investigate the involvement of
      cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG)
      production by human periodontal ligament (PDL) fibroblasts stimulated with a
      proinflammatory cytokine, inerleukin-1beta (IL-1beta), and to examine the effect
      of interleukin-4 (IL-4), a Th2 cytokine, and interferon-gamma (IFN-gamma), a Th1
      cytokine, on PG production by the cells. IL-1beta-stimulated PDL fibroblasts
      produced prostaglandin E2 (PGE2) in a time-dependent manner. Indomethacin, a non
      selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor,
      completely inhibited PGE2 production by IL-1beta-stimulated cells. Northern blot
      analysis showed that COX-2 mRNA was detected in IL-1beta-stimulated PDL cells,
      although not detected in unstimulated cells, while expression of COX-1 mRNA was
      in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA
      expression, COX activity and PGE2 production in IL-1beta-stimulated cells. IL-4
      and IFN-gamma suppressed PGE2 production by IL-1beta-stimulated PDL fibroblasts,
      but COX activity enhanced by IL-1beta treatment was significantly inhibited by IL
      4, not by IFN-gamma. Northern blot analysis showed that IL-4 depressed COX-2 mRNA
      expression with no effect on COX-1 mRNA expression. On the other hand, IFN-gamma
      had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2
      is primarily responsible for PGE2 production by IL-1beta-stimulated human PDL
      fibroblasts and that IL-4 inhibited PGE2 production by IL-1beta-stimulated PDL
      fibroblasts through down-regulation of COX-2 expression, while IFN-gamma
      suppressed the PGE2 production with no effect on COX-2 expression.

PMID- 10065758
TI  - Heterogeneity of procoagulant activity and cytokine release in subpopulations of
      alveolar macrophages and monocytes.
AB  - We have studied the expression of tissue factor (TF) and fibrinopeptide A (FPA)
      generation as well as the release capacity of TNF-alpha, IL-1beta, and IL-6 in
      density-defined subpopulations of alveolar macrophages (AM) and monocytes (Mo).
      TF was equally expressed on all AM subpopulations and Mo, while the FPA-forming
      capacity was at the same level in low density AM as in Mo and was significantly
      (P < 0.05) higher in low density AM than in high density AM. The
      lipopolysaccharide (LPS)-induced release of TNF-alpha was higher (P < 0.05) in
      high density AM than in low density AM and in Mo. IL-1beta release was
      undetectable in unstimulated AM and in LPS-stimulated low density AM, while the
      LPS-induced IL-1beta release in high density AM was low compared to the levels
      demonstrated in Mo. LPS-stimulated IL-6 release was not distinctively different
      in the AM subpopulations and Mo. The presented study showed that FPA generation
      and LPS-stimulated TNF-alpha release were dependent on the density (i.e.,
      maturity) of AM. This implies that a skewed distribution of AM subpopulations
      induced by disease processes may profoundly influence the inflammatory reactions,
      including extravascular activation of coagulation.

PMID- 10065759
TI  - Interleukin-3 production by mast cells from human lung.
AB  - The cytokine interleukin (IL)-3 is important in the proliferation of eosinophils
      and basophils in the airway. We investigated IL-3 production by human lung mast
      cells as a possible mechanism of the airway inflammation constituting the late
      asthmatic response. Mast cells were purified using affinity magnetic selection
      with the monoclonal antibody YB5.B8 and then stimulated with anti-human IgE
      antibody. IL-3 release was detectable by enzyme-linked immunosorbent assay 8 h
      after anti-IgE stimulation. IL-3 release 24 h after anti-IgE stimulation was
      significantly greater than its controls. By reverse transcription-polymerase
      chain reaction, IL-3 mRNA was detected weakly 2 h after anti-IgE stimulation,
      peaking at 4 h and waning at 8 h. Immunocytochemistry to localize IL-3
      demonstrated mast cell staining. These results suggest that mast cells release IL
      3 in response to high-affinity IgE receptor.

PMID- 10065760
TI  - Exogenous nitric oxide increases neutrophil adhesion to cultured human
      endothelial monolayers through a protein kinase G dependent mechanism.
AB  - Endothelial-neutrophil adhesion is a critical step in acute inflammatory
      diseases, which is mediated in part by P-selectin and platelet-activating factor
      (PAF). Nitric oxide (NO) is well known as an endogenous second messenger derived
      from endothelial cells, and regulates many important physiological events,
      however, the direct effects of NO on endothelial-neutrophil adhesion is less well
      understood. The objective of this study was to examine whether, and how
      relatively high levels of exogenous NO increases neutrophil adhesion with respect
      to P-selectin and PAF. Endothelial monolayers were exposed to chemical agents for
      30 min, and the adhesion of 51Cr-labeled neutrophils measured in a static
      adhesion assay. Spermine-NONOate (SNO), an NO donor, significantly increased
      neutrophil adhesion and expression of P-selectin at a concentration of 1 mM. SNO
      (1 mM)-mediated neutrophil adhesion was significantly inhibited by a protein
      kinase G inhibitor, KT5823 (0.5 microM), but not by a classical protein kinase C
      inhibitor, Go6976 (10 nM), a tyrosine kinase inhibitor, genistein (1 microM), or
      a protein kinase A inhibitor, H-89 (0.1 microM). P-selectin surface expression
      induced by 1 mM SNO was also significantly inhibited by 0.5 microM KT5823.
      Conversely, a cytoplasm calcium chelator, TMB-8 (0.1 mM), significantly
      exacerbated both the neutrophil adhesion and P-selectin expression induced by
      SNO. WEB 2086 (10 microM), a PAF receptor antagonist, blocked neutrophil
      adhesion, but did not block P-selectin expression induced by SNO. These data
      suggest that NO increases endothelial-neutrophil adhesion through protein kinase
      G-mediated P-selectin mobilization to the cell surface and endothelial PAF
      synthesis.

PMID- 10065761
TI  - The effects of IB4, a monoclonal antibody to the CD18 leukocyte integrin on
      phorbol myristate acetate (PMA)-induced polymorphonuclear leukocyte (PMN)
      accumulation and endothelial injury in rabbit lungs.
AB  - A model of acute lung injury induced by intravenous phorbol myristate acetate
      (PMA) is described. The model is characterized by the accumulation of
      polymorphonuclear leukocytes (PMNs) and a hemorrhagic edema in bronchoalveolar
      lavage (BAL) fluid when measured 6 h following the administration of PMA (60
      microg/kg, i.v.). It was also determined that PMA induces acute leukopenia and
      neutropenia which were maximal at 5 min following the injection of PMA and were
      sustained for at least 6 h, with circulating leukocyte numbers returning to
      control values by 24 h. The extents to which the inflammatory and systemic
      changes induced by PMA were dependent on the surface expression on leukocytes of
      the beta2-integrins was assessed by comparing responses to PMA in control animals
      and animals pretreated with the anti-CD18 monoclonal antibody IB4. The
      administration of IB4 (1 mg/kg, i.v.) 15 min before PMA did not alter the time
      course or extent of PMA-induced leukopenia and neutropenia. In contrast IB4
      administration (0.1 to 1 mg/kg) produced a dose dependent inhibition of PMN
      accumulation and plasma extravasation measured in BAL fluid. IB4 (1 mg/kg)
      completely inhibited PMA evoked increases in plasma extravasation (94.5 +/- 1.7%,
      N = 4) and hemorrhage (95.2 +/- 2.1%, N = 4) whereas PMN accumulation in BAL
      fluid was inhibited by 77.8 +/- 3.8% (mean +/- SEM, N = 4). Thus, a small, but
      reproducible, component of the PMA-induced PMN accumulation was not inhibited
      using this regimen of IB4 administration. If IB4 administration was delayed for 3
      h post injection of PMA and bronchoalveolar lavage performed 3 h later, the
      extents of PMN accumulation and edema formation were similar to those observed 3
      h following PMA challenge in control animals not dosed with IB4. This suggests
      that administration of IB4 during an ongoing inflammatory response is capable of
      preventing the further development of inflammatory changes and further supports
      the therapeutic potential of CD18 blockade in conditions such as adult
      respiratory distress syndrome.

PMID- 10065762
TI  - Neutrophils injure bronchial epithelium after ozone exposure.
AB  - Neutrophil (PMN) influx is an early, prominent finding in the airways of humans
      after experimental inhalation of ozone (O3), however the potential for PMN to
      contribute to epithelial injury in this setting is unknown. Bronchial epithelial
      cells of the human BEAS 2B R1.4 cell line or primary human bronchial epithelial
      cells underwent DNA labeling by incubation with BrdU. Monolayers were exposed to
      O3 (0.05 to 1 ppm) or filtered air for 60 min., and subsequently incubated with
      PMN for 2 h. Epithelial cell cytolysis was significant only in BEAS exposed to O3
      and co-cultured with PMN. Apoptosis was maximal in BEAS exposed to O3 + PMN.
      Primary bronchial epithelial cells were resistant to injury; no cytolysis was
      detected, and apoptosis was detected only after treatment with 10 mM H2O2.
      Neutrophils may increase damage to the respiratory epithelium after O3 exposure,
      but primary bronchial epithelial cells are resistant to PMN and ozone induced
      injury.

PMID- 10065763
TI  - The CC chemokine MIP-1alpha induces a selective monocyte infiltration following
      intradermal injection into nonhuman primates.
AB  - The in vitro chemotactic activity of chemokines have been well documented.
      However, study of their in vivo effects where components of rolling, adherence
      and diapedesis are pre-requisites to leukocyte infiltration have not been
      examined in higher species. In this study, we examined the biological activity of
      the CC chemokine, MIP-1alpha, in rhesus monkeys. Following an intradermal
      injection, a significant cellular infiltrate and an increase in the number of
      inflamed vessels were observed. This response peaked at 24 h and was sustained
      for up to 48 hours after injection. Phenotypically, the specific infiltrate
      consisted exclusively of CD68+ monocytes with no increase in other cell types
      over the saline injected controls. These studies represent the first examination
      of the in vivo effects of MIP-1alpha in higher species and indicate that MIP
      1alpha is a selective monocyte recruiting agent in vivo.

PMID- 10065764
TI  - Different reactions of aortic and venular endothelial cell monolayers to
      histamine on macromolecular permeability: role of cAMP, cytosolic Ca2+ and F
      actin.
AB  - Endothelial cells assume a central role in the one process that the permeation of
      microvessels is accelerated in case of inflammation. We studied the effect of
      histamine on endothelial permeability, [Ca2+]i, cAMP and F-actin, using same
      origin aortic and venular cultured endothelial monolayers. When HUVEC were
      treated with histamine (10(-7)-10(-5) M), permeability of FITC-dextran (molecular
      weight 70,000) and [Ca2+]i were increased, while cAMP content was unchanged, and
      F-actin content was reduced. When bovine vein-derived endothelial cells were
      treated with histamine, [Ca2+]i was increased via H1 receptors, but permeability
      and F-actin content were not altered. When human aorta-derived endothelial cells
      were, [Ca2+]i was increased via H1 receptors and cAMP content was increased via
      H2 receptors, while permeability and F-actin content were not changed. When
      bovine aorta-derived endothelial cells were, cAMP and F-actin content were
      increased, while permeability was reduced. These findings suggest that
      endothelial cells derived from different tissues clearly showed the different
      reactions to histamine, the increase in [Ca2+]i led to the increase in
      endothelial permeability, while the increase in cAMP levels led to the reduction
      in permeability, and finally, F-actin regulated endothelial macromolecular
      permeability.

PMID- 10065765
TI  - Communications to the Annual Conference of the British Association of Sport and
      Exercise Sciences (BASES). University College Worcester, Worcester, 6-8 September
      1998.

PMID- 10065766
TI  - Placebos in medicine.
AB  - Although placebo may be defined as a treatment that does not have a specific
      effect on the illness for which it is being used, or as an intervention for which
      there is no scientific theory explaining its mechanism of action, placebo can be
      an effective therapeutic intervention. Placebo can be administered as a drug or
      as a procedural intervention. Multiple factors affect the ultimate intensity of
      the placebo response. One of these factors is the approach taken by the health
      care provider in administering an intervention. The medical literature is replete
      with clinical studies showing beneficial results of placebo administration.
      Physicians should attempt to better understand placebo to harness its beneficial
      effects, avoid nocebo or negative effects, and maximize the placebo response.

PMID- 10065767
TI  - Brain-gut axis and mucosal immunity: a perspective on mucosal
      psychoneuroimmunology.
AB  - The role of the brain-gut axis has traditionally been investigated in relation to
      intestinal motility, secretion, and vascularity. More recently, the concept of
      brain-gut dialogue has extended to the relationship between the nervous system
      and mucosal immune function. There is compelling evidence for a reciprocal or bi
      directional communication between the immune system and the neuroendocrine
      system. This is mediated, in part, by shared ligands (chemical messengers) and
      receptors that are common to the immune and nervous systems. Although the concept
      of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in
      the context of the systemic immune system, it is likely to have special
      significance in the gut. The mucosal immune system is anatomically, functionally,
      and operationally distinct from the systemic immune system and is subject to
      independent regulatory signals. Furthermore, the intestinal mucosal immune system
      operates in a local milieu that depends on a dense innervation for its integrity,
      with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview
      of evidence for the biologic plausibility of a brain-gut-immune axis is presented
      and its potential relevance to mucosal inflammatory disorders is discussed.

PMID- 10065768
TI  - Stress and mind-body impact on the course of inflammatory bowel diseases.
AB  - At present, the medical management of inflammatory bowel diseases (IBD) including
      Crohn's disease and ulcerative colitis, are focused on topical, locally active
      antiinflammatories and systemic immunosuppressives, which are thought to exert
      their targeted effects in the gastrointestinal mucosa. There is a paucity of
      controlled trials assessing the impact of mind, central nervous system (CNS), and
      neuromodulation on the overly active immune response in the intestinal mucosa.
      Patients and their physicians have long been aware of a strong association
      between attitude, stress, and flares of their IBD. Although reports to date
      remain mostly anecdotal, the degree to which mind-body influences and stress
      impact levels of local inflammation deserves closer attention with the aim of
      identifying contributing mechanisms, which may highlight new therapeutic
      interventions, as well as assist in identifying particular subsets of patients
      that may respond to novel forms of adjunctive treatments for IBD, including
      hypnosis, meditation, neuropeptide receptor modulation, and cortisol-releasing
      factor (CRF) modulation.

PMID- 10065769
TI  - Psychoneuroimmunology update.
AB  - Psychoneuroimmunology is the scientific field that investigates linkages between
      the brain, behavior, and the immune system and the implications of these linkages
      for physical health and disease. Recent evidence suggests that both naturalistic
      and laboratory stressors can alter enumerative and functional aspects of the
      human immune system. Chronic stress may increase vulnerability to infectious
      disease; however, the role of stress in the course of inflammatory bowel disease
      remains unclear. Because there are large individual differences in psychological
      response to stress, it is important to consider the role of cognitive and
      affective responses to stress. Depression has been associated with functional
      immune decrements and immune overactivation. Cognitive states such as perceived
      control, views of the self, and views of the future have been associated with
      immune parameters and health in some studies. Very few controlled clinical trials
      have been conducted to determine if psychosocial interventions can impact the
      immune system and the progression of medical conditions. There is suggestive
      evidence for the health benefits of relaxation training, cognitive-behavioral
      stress management, and support groups; but, there is little research on many
      other psychosocial interventions in widespread use for medical conditions. An
      evidence-based discussion of this research literature with interested patients
      may help them make informed decisions regarding adjunctive treatments.

PMID- 10065770
TI  - The management of medically unexplained symptoms.
AB  - Medically unexplained symptoms occur in up to 50% of new medical out-patients.
      Health care seeking may not be related to the presence of physical disease but
      may reflect social problems, psychological disturbance, or frank psychiatric
      disorder. Management of unexplained physical symptoms depends on the duration of
      symptoms. If acute, exclusion of physical disease, as well as providing
      symptomatic care, is a priority. The patient's fears of illness need to be
      addressed and an explanation in simple terms of the symptoms provided. Adverse
      life situations should be identified and, where possible, rectified. Psychiatric
      disorders require appropriate treatment. When symptoms are chronic, conservative
      management is required to contain the symptoms and avoid iatrogenic problems.

PMID- 10065771
TI  - Refractory gastrointestinal symptoms: a combined medical psychiatric approach.
AB  - Gastroenterology has always been a collaborative specialty. Through the years,
      gastroenterologists have created important partnerships with pathologists,
      radiologists, surgeons, gynecologists, and pediatricians. These collaborative
      relationships have greatly enhanced patient care and research. This article
      reviews the literature on psychiatric comorbidity in the medical setting and
      gastroenterology practice in particular. The ability to recognize psychiatric
      comorbidity and relate it to the patient's presenting gastrointestinal (GI)
      complaint can pay great dividends for patients. The ability to apply these
      observations to help facilitate psychiatric collaboration and specifically, to
      initiate behavioral treatment, represents a new dimension in the care of chronic
      GI disorders. Finally, the relationship between physical and sexual abuse and GI
      illness and the usefulness of psychiatric interventions in the treatment of
      chronic GI disorders is reviewed in detail.

PMID- 10065772
TI  - The role of luteinizing hormone in folliculogenesis and ovulation induction.
AB  - OBJECTIVE: To review the physiologic, pathophysiologic, and clinical roles of LH
      in follicle and oocyte development and maturation and to assess the effects of LH
      content in exogenous gonadotropin preparations used for ovulation induction.
      DESIGN: Critical review of the scientific literature devoted to folliculogenesis.
      Evaluation of comparison studies that used different gonadotropin preparations
      for ovulation induction. CONCLUSION(S): Folliculogenesis and oocyte maturation
      are complex processes that require the action of both LH and FSH. Luteinizing
      hormone is essential to provide the androgen substrate for estrogen synthesis,
      which in turn contributes to oocyte maturation and may play a relevant role in
      optimizing fertilization and embryo quality. Although the excessive LH secretion
      that is present in some disorders is detrimental to reproductive function, this
      is not applicable to ovulation induction with hMG because this menotropin does
      not increase daily plasma LH levels. The results of ovulation induction with hMG
      or FSH-only regimens did not differ in studies conducted in patients with
      polycystic ovary syndrome and in most studies conducted in ovulatory women
      undergoing assisted reproductive techniques; conversely, hMG was clearly superior
      to purified FSH for the treatment of hypogonadotropic hypogonadism. Miscarriage
      rates were not affected by the use of hMG. Thus, low but detectable LH
      concentrations positively influence the outcome of ovulation induction in
      patients with ovulatory disorders and women undergoing assisted reproductive
      techniques.

PMID- 10065773
TI  - Sexism and racism in preconceptive trait selection.

PMID- 10065774
TI  - Political correctness and the abridgment of reproductive choice.

PMID- 10065775
TI  - Add-back therapy and gonadotropin-releasing hormone agonists in the treatment of
      patients with endometriosis: can a consensus be reached? Add-Back Consensus
      Working Group.
AB  - OBJECTIVE: To reach a consensus on the role of add-back therapy for patients with
      endometriosis administered GnRH agonists (GnRH-a). DESIGN: Results of consensus
      conference reviewing MEDLINE search of English language abstracts of both
      prospective and retrospective series. SETTING: Consensus conference of 31
      specialists in gynecologic surgery and reproductive endocrinology. PATIENT(S):
      Patients with symptomatic endometriosis who were candidates for GnRH-a therapy in
      treatment courses ranging in duration from 6 to 12 months. INTERVENTION(S): Oral
      steroidal and nonsteroidal add-back regimens. MAIN OUTCOME MEASURE(S): Alteration
      in painful symptoms, extent of disease, vasomotor symptoms, bone mineral density,
      and serum lipid profile. RESULT(S): When added to GnRH-a for 6 months, both 2.5
      mg of norethindrone and 0.625 mg of conjugated equine estrogens with 5 mg/d of
      medroxyprogesterone acetate provide effective relief of vasomotor symptoms and
      decrease but do not eliminate bone mineral density loss. During 12 months of GnRH
      a therapy, bone mineral density loss is eliminated effectively with an add-back
      of 5 mg of norethindrone acetate alone or in conjunction with low-dose conjugated
      equine estrogens. Organic bisphosphonates also may play a role. CONCLUSION(S): In
      patients with symptomatic endometriosis, the efficacy of GnRH agonists may be
      preserved and therapy prolonged while overcoming hypoestrogenic side effects with
      the use of appropriate add-back regimens.

PMID- 10065776
TI  - Role of the mutations Trp8 => Arg and Ile15 => Thr of the human luteinizing
      hormone beta-subunit in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the clinical significance of LH in the form of a mutant
      beta-subunit in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective,
      controlled study. SETTING: University hospital. PATIENT(S): Thirty healthy women
      and 30 women with PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal
      findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in
      the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the
      use of polymerase chain reaction and subsequent restriction fragment length
      polymorphism. MAIN OUTCOME MEASURE(S): Serum levels of gonadotropins, androgens,
      E2, and prolactin were determined, and the results of restriction fragment length
      polymorphism were analyzed. RESULT(S): Five women in the control group and one
      woman in the PCOS group were found to be affected by the LHbeta gene mutations.
      No difference was observed in serum androgen and E2 levels between the affected
      women and 25 healthy women who were homozygous for the wild-type LH. However,
      women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having
      mutant LH. CONCLUSION(S): The frequency of LH mutations in women with PCOS is
      similar to that in healthy women. The presence of the variant does not cause any
      significant change in serum levels of androgens and E2.

PMID- 10065777
TI  - Polymorphism T-->C (-34 bp) of gene CYP17 promoter in Greek patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the frequency of T-->C substitution (-34 bp) of gene
      CYP17 promoter in Greek patients with polycystic ovary syndrome (PCOS) and to
      elucidate its role in the pathogenesis of the syndrome. DESIGN: Follow-up study.
      SETTING: Academic research setting. PATIENT(S): Fifty patients with PCOS and 50
      healthy women. INTERVENTION(S): Body mass index and the waist-hip ratio were
      determined for each woman. Blood samples were obtained for DNA analysis and
      hormone estimates. MAIN OUTCOME MEASURE(S): Serum total T levels. RESULT(S):
      Seventeen patients (34%) did not carry the base pair substitution (genotype A1A1)
      and their mean (+/- SD) total T level was 75.7+/-32.2 ngl/dL, 29 patients (58%)
      were heterozygous carriers of the A2 allele (genotype A1A2) and their mean total
      T level was 77.8+/-29.9 ng/dL, and 4 patients (8%) carried the A2 allele in
      homozygosity (genotype A2A2) and their mean total T level was 87.0+/-2.8 ngl/dL.
      Twenty-two controls had the genotype A1A1 (44%) and their mean total T level was
      39.1+/-15.5 ng/dL, whereas 28 (56%) had the genotype A1A2 and their mean total T
      level was 44.9+/-22.1 ng/dL. Homozygosity of the polymorphic A2 allele was not
      observed in controls, and this difference (8% versus 0%) was statistically
      significant. CONCLUSION(S): Although this base pair substitution is not the
      primary genetic defect in PCOS, it may aggravate the clinical picture of
      hyperandrogenemia, particularly when homozygosity exists.

PMID- 10065778
TI  - Dopamine D3 receptor polymorphism is not associated with the polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine if a polymorphism of the dopamine D3 receptor gene (2
      allele), which has been reported previously to be associated with polycystic
      ovary syndrome (PCOS) in a population of United States Hispanic women, is
      associated with the disorder in the southeastern United States. DESIGN:
      Prospective case-control study. SETTING: University reproductive endocrinology
      laboratory and outpatient clinic. PATIENT(S): Consecutive patients of non
      Hispanic white race diagnosed with PCOS (n = 152) and healthy controls (n = 96).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patient and control dopamine D3
      receptor genotypes, with the 1 allele representing the wild type and the 2 allele
      denoting a highly prevalent polymorphism. RESULT(S): No difference was noted in
      the distribution of the three dopamine D3 receptor genotypes (i.e., 1:1, 1:2, and
      2:2) among PCOS patients as compared with controls. Furthermore, in contrast to a
      previous report, the 2:2 genotype was not more prevalent among PCOS patients than
      among controls. CONCLUSION(S): Our population of non-Hispanic white women from
      the southeastern United States did not demonstrate an association between a
      dopamine D3 receptor polymorphism and PCOS.

PMID- 10065779
TI  - Adrenal dynamic responses to physiologic and pharmacologic adrenocorticotropic
      hormone stimulation before and after ovarian steroid modulation in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To test the hypothesis that in women with polycystic ovary syndrome
      (PCOS), adrenal cytochrome P450c 17alpha activity is different after physiologic
      vs. pharmacologic ACTH stimulation and that ovarian activity promotes adrenal
      hyperactivity that is different after physiologic vs. pharmacologic ACTH
      stimulation. DESIGN: Prospective controlled pilot study. SETTING: Reproductive
      endocrinology unit of an academic medical center. PATIENT(S): Six women with PCOS
      who had adrenal hyperandrogenism were compared with four women with normal
      ovulation. INTERVENTION(S): Adrenal dynamic blood sampling was performed before
      and after 6 months of GnRH agonist administration. MAIN OUTCOME MEASURE(S):
      Comparison of physiologic and pharmacologic ACTH-stimulated levels of
      progesterone, 17-hydroxyprogesterone, and androgens before and after ovarian
      steroid modulation. RESULT(S): In women with PCOS, exaggerated responses of
      androstenedione and 11beta-hydroxyandrostenedione as well as elevated ratios of
      17-hydroxyprogesterone to progesterone and of androstenedione to 17
      hydroxyprogesterone after physiologic ACTH stimulation did not persist after GnRH
      agonist administration. Three of the six women with PCOS had an increased
      response of androstenedione and a ratio of androstenedione to 17
      hydroxyprogesterone that were >2 SD above the mean of those in the women with
      normal ovulation after pharmacologic ACTH stimulation; this finding persisted
      after GnRH-agonist administration. CONCLUSION(S): In women with PCOS, increases
      in adrenal androgen sensitivity after physiologic ACTH stimulation reflected in
      both arms of cytochrome P450c 17alpha activity may be influenced by ovarian
      activity. However, 17,20-lyase hyperactivity in a subset after pharmacologic ACTH
      stimulation may be an intrinsic adrenal disorder.

PMID- 10065780
TI  - Treatment of hirsutism: comparisons between different antiandrogens with central
      and peripheral effects.
AB  - OBJECTIVE: To compare the clinical and endocrinologic effects of cyproterone
      acetate (CPA), an antiandrogen with progestational activity; flutamide, a
      nonsteroidal antiandrogen, and finasteride, an inhibitor of 5alpha-reductase.
      DESIGN: Randomized, open, controlled clinical study. SETTING: Department of
      Obstetrics and Gynecology, University of Pisa, Pisa, Italy. PATIENT(S): Forty
      five hirsute women were enrolled in the study: 29 were hyperandrogenic and 16 had
      idiopathic hirsutism. Three women dropped out of the study. INTERVENTION(S):
      Women were randomly treated with finasteride (5 mg/d; n = 14), CPA (25 mg plus
      ethinyl E2 (EE); n = 13), or flutamide (500 mg/d; n = 15) for 1 year. MAIN
      OUTCOME MEASURE(S): Hirsutism was assessed using the Ferriman-Gallwey method.
      Levels of total and free T, androstenedione (A), DHEAS, sex hormone-binding
      globulin, dihydrotestosterone, and 3alpha-androstanediol glucuronide were
      evaluated at the beginning of the study and every 3 months. RESULT(S): Treatment
      with finasteride, flutamide, and CPA significantly decreased the Ferriman-Gallwey
      score. The percent decreases in the hirsutism score induced by the different
      treatments were similar. Treatment with CPA plus EE significantly decreased
      levels of total and free T, A, dihydrotestosterone, and 3alpha-androstanediol
      glucuronide. These parameters were unchanged with flutamide therapy. Finasteride
      significantly increased total T levels but reduced dihydrotestosterone and 3alpha
      androstanediol glucuronide concentrations. CONCLUSION(S): Finasteride, CPA, and
      flutamide are equally effective in decreasing hirsutism, despite different
      mechanisms of action.

PMID- 10065781
TI  - Octreotide is not useful for clomiphene citrate resistance in patients with
      polycystic ovary syndrome but may reduce the likelihood of ovarian
      hyperstimulation syndrome.
AB  - OBJECTIVE: To determine whether octreotide is effective for ovulation induction
      in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate
      resistance or for reduction of the risk of ovarian hyperstimulation syndrome
      (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo
      controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S):
      Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S):
      The patients were assigned randomly to receive either octreotide or placebo.
      Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg.
      Patients at risk for the development of OHSS received urinary FSH for ovulation
      induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of
      OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like
      growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2,
      LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting
      insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and
      urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding
      protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached
      ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated
      cycles, patients who received octreotide had significantly lower E2 levels at the
      time of hCG administration and fewer mature follicles. No cases of OHSS occurred
      in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide
      was no more effective than placebo for clomiphene citrate resistance in patients
      with PCOS, but it did reduce E2 levels and follicle numbers when combined with
      urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with
      PCOS.

PMID- 10065782
TI  - Obesity regulates bioavailable testosterone levels in women with or without
      polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate [1] the effects of levels of sex hormone-binding globulin
      (SHBG), albumin, and total testosterone on the distribution of testosterone
      between SHBG-bound and non-SHBG-bound fractions; [2] the independent effects of
      polycystic ovary syndrome (PCOS) and body mass index on serum levels of total
      testosterone, non-SHBG-bound testosterone, SHBG, and albumin; and [3] the
      usefulness of levels of total testosterone and non-SHBG-bound testosterone and of
      the free androgen index in the diagnosis of PCOS. DESIGN: Retrospective clinical
      study. SETTING: An academic research environment. PATIENT(S): Forty-three women
      with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and
      without hirsutism served as controls. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Levels of non-SHBG-bound testosterone, total testosterone, SHBG, and
      albumin in serum. RESULT(S): Levels of total testosterone and non-SHBG-bound
      testosterone, and the free androgen index were higher in patients with PCOS than
      in healthy controls. PCOS did not have an effect on the levels of SHBG or
      albumin, or on the percentage of non-SHBG-bound testosterone. Levels of SHBG and
      albumin were inversely related to body mass index. The percentage and
      concentration of non-SHBG-bound testosterone and the free androgen index were
      directly related to body mass index. Hirsutism did not have an effect on any
      outcome measure. CONCLUSION(S): The distribution of total testosterone into SHBG
      bound and non-SHBG-bound fractions is associated with body mass index, not with
      PCOS. The high levels of non-SHBG-bound testosterone and the high free androgen
      index in patients with PCOS reflect mainly high levels of total testosterone.
      Thus, the measurement of levels of non-SHBG-bound testosterone and the
      calculation of the free androgen index provide no further information in the
      diagnosis of PCOS beyond that provided by the measurement of levels of total
      testosterone.

PMID- 10065783
TI  - Influence of body mass on the hypothalamic-pituitary-adrenal-axis response to
      naloxone in patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the influence of body mass on the hypothalamic-pituitary
      adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS).
      DESIGN: Controlled clinical study. SETTING: Academic research environment.
      PATIENT(S): Ten lean and 10 obese women with PCOS compared with 7 lean and 8
      obese control subjects matched for body mass index. INTERVENTION(S): Each patient
      received an IV bolus of naloxone at a dosage of 125 microg/kg. MAIN OUTCOME
      MEASURE(S): Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and
      120 minutes after injection: ACTH and cortisol levels were measured in all plasma
      samples. RESULT(S): No significant differences were found in the ACTH and
      cortisol responses to opioid blockade between lean women with PCOS and lean as
      well as obese control subjects; conversely, obese patients with PCOS showed a
      higher ACTH and cortisol responses to naloxone compared with all other groups.
      CONCLUSION(S): Hypothalamic-pituitary-adrenal-axis abnormalities of PCOS may be
      central in origin and abdominal obesity seems to play a key role in the HPA-axis
      hyperactivity of women with PCOS when naloxone is administered.

PMID- 10065784
TI  - Prospective randomized trial comparing the outcome and cost of in vitro
      fertilization with that of a traditional treatment algorithm as first-line
      therapy for couples with infertility.
AB  - OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm
      results in better outcome and/or lower cost when used as first-line therapy for
      couples with infertility. DESIGN: Prospective, randomized clinical study.
      SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly
      diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were
      randomized to undergo either IVF (group 1, n = 46) or a standard infertility
      treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN
      OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment,
      and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in
      group 1. Costs per couple were not statistically different, although a trend
      toward higher costs was apparent in group 1, reflected by a higher median cost
      per clinical pregnancy established and a higher cost per month of treatment.
      Whereas cost differences between the groups diminished over time, pregnancy rates
      remained the same. CONCLUSION(S): In vitro fertilization currently does not
      represent an appropriate first-line treatment option for couples with
      infertility. The use of a standard infertility treatment algorithm results in a
      higher pregnancy rate and lower cost and therefore should be the preferred
      treatment approach.

PMID- 10065785
TI  - Endometrial wave direction switch and the outcome of in vitro fertilization.
AB  - OBJECTIVE: To describe endometrial wavelike activity, endometrial thickness and
      texture in IVF cycles, and to relate them to IVF outcome. To evaluate wave
      patterns on the day of hCG administration as a predictor of IVF outcome. DESIGN:
      Ultrasound study. SETTING: University hospital-based infertility clinic.
      PATIENT(S): Twenty-eight women undergoing IVF. INTERVENTION(S): Ultrasound
      examinations were performed at five fixed moments (start ovarian stimulation, hCG
      administration, ovum pickup (OPU), ET, and 7 days after hCG administration) and
      at three variable moments in the stimulation period in the cycle. The OPU was
      performed 2 days after hCG administration; ET was performed 2 or 3 days after
      that. MAIN OUTCOME MEASURE(S): Endometrial wave pattern, thickness, texture, IVF
      outcome. RESULT(S): Embryo transfer was performed in 22 cycles. In 73% of the
      cycles a wave direction switch (WDS) from fundus to cervix (FC) to cervix to
      fundus (CF) occurred before OPU. Eleven (50%) patients became pregnant.
      Significantly more FC waves persisted until hCG administration in the cycles in
      which the patients conceived. Endometrial thickness and texture were unrelated to
      IVF outcome. CONCLUSION(S): Endometrial wave pattern is associated with pregnancy
      in IVF. The persisting presence of FC waves until hCG administration (a late WDS)
      predicts a favorable IVF outcome.

PMID- 10065786
TI  - The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies
      investigating the role of interleukin-1beta, interleukin-6, and vascular
      endothelial growth factor.
AB  - OBJECTIVE: To evaluate systemic and ovarian changes in levels of interleukin (IL)
      1beta, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG
      administration to determine which may be the potential initiator of vascular
      effects and to identify the main source of the substance; to evaluate serum and
      follicular fluid levels of these cytokines as markers of ovarian hyperstimulation
      syndrome (OHSS), and to compare levels of these cytokines under basal conditions
      in women with normal ovulation and those with polycystic ovary syndrome (PCOS).
      DESIGN: Prospective controlled study. SETTING: In vitro fertilization program at
      the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): Women
      undergoing IVF, in whom the first two study objectives were analyzed, and women
      with normal ovulation and patients with PCOS undergoing retrieval of immature
      oocytes in natural cycles or cycles stimulated for IUI but cancelled during
      induction of ovulation, in whom the third study objective was analyzed.
      INTERVENTION(S): Serum was collected before and after hCG administration, and
      follicular fluid was collected at ovum pick-up. MAIN OUTCOME MEASURE(S): Serum
      and follicular fluid levels of IL-1beta, IL-6, and VEGF. RESULT(S): There was a
      significant increase in serum VEGF levels after hCG administration in patients
      who were at risk for OHSS compared with those who were not at risk for OHSS.
      Significantly lower VEGF levels were found in the follicular fluid of patients
      who were at risk; this decrease was the only useful marker to discriminate
      between the two groups. Moreover, both groups had similar cytokine production
      under basal conditions. An increase in serum E2 occurred coincident with a
      decrease in IL-1beta, IL-6, and VEGF in patients with PCOS. CONCLUSION(S):
      Vascular endothelial growth factor seems to be the mediator of hCG on the
      vascular tree. There was an early systemic increase in VEGF that may have
      significance in the development of OHSS. A decrease in the follicular fluid VEGF
      concentration is a valid marker to identify women in whom OHSS will develop. The
      pattern of cytokine release in patients with PCOS under basal conditions was not
      different from that in women with normal ovulation.

PMID- 10065787
TI  - Menstrual cycle pattern and fertility: a prospective follow-up study of pregnancy
      and early embryonal loss in 295 couples who were planning their first pregnancy.
AB  - OBJECTIVE: To characterize how the menstrual cycle pattern relates to fertility
      regardless of potential biases caused by inappropriate coital timing during the
      menstrual cycle or early embryonal loss. DESIGN: Prospective follow-up study.
      SETTING: Healthy couples recruited throughout Denmark. PATIENT(S): Two hundred
      ninety-five couples who were planning their first pregnancy were followed up from
      the discontinuation of birth control until a pregnancy was recognized within six
      menstrual cycles. Early embryonal losses were detected by changes in urinary hCG
      levels. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The probability of
      pregnancy occurring within one menstrual cycle (fecundity). RESULT(S): In women
      who had a cycle length that differed by >10 days from the usual cycle length,
      fecundity was approximately 25% that of women who had no variation (odds ratio
      0.25, 95% confidence interval 0.09-0.68). When the combined effect of cycle
      variation and cycle length was assessed, cycle variation was a persistent strong
      predictor of fecundity. CONCLUSION(S): The mechanisms of the present findings
      probably are female functional disturbances in ovulation, conception,
      implantation, or sustained pregnancy, linked with variable menstrual cycle
      length. Thus, identification of medical and environmental causes of abnormal
      menstrual cycle patterns may provide clues to the causes of infertility.
      Moreover, the menstrual cycle pattern also should be taken into consideration in
      the clinical decision-making process.

PMID- 10065788
TI  - Two-color fluorescence staining of lectin and anti-CD46 antibody to assess
      acrosomal status.
AB  - OBJECTIVE: To examine potential methods for distinguishing between the acrosome
      reaction and acrosomal loss. DESIGN: Prospective randomized study. SETTING:
      Department of Obstetrics and Gynecology, Osaka University Hospital, Suita, Japan.
      PATIENT(S): Five healthy volunteers and 34 patients with normozoospermia who were
      participating in an IVF program. INTERVENTION(S): Semen samples were collected
      from the volunteers before the hamster egg penetration assay and from the
      patients at the time of IVF. MAIN OUTCOME MEASURE(S): The numbers of oocytes
      penetrated and spermatozoa bound were determined with the hamster egg penetration
      assay. Acrosomal status was assessed with two-color fluorescence staining using
      fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and
      MH61 (anti-CD46 monoclonal antibody) with Texas red-conjugated antimouse
      immunoglobulin G antiserum. RESULT(S): The MH61 monoclonal antibody inhibited the
      penetration of human spermatozoa into hamster oocytes but did not reduce the
      number of spermatozoa bound to the zona-free hamster oocytes. Two-color
      fluorescence staining revealed four staining patterns of the acrosomal region.
      The percentage of PSA-negative/CD46-positive spermatozoa increased to a greater
      extent than that of PSA-negative/CD46-negative spermatozoa with an increase in
      the incubation time. CONCLUSION(S): Two-color fluorescence staining with FITC-PSA
      and the anti-CD46 monoclonal antibody may be useful for distinguishing between
      the acrosome reaction and acrosomal loss.

PMID- 10065789
TI  - Characterization of a potent sperm-agglutinating monoclonal antibody and its
      cognate antigens.
AB  - OBJECTIVE: To identify sperm antigens that are capable of eliciting infertility
      related sperm-agglutinating antibodies. DESIGN: In vitro laboratory experiments.
      SETTING: University research laboratory. PATIENT(S): Fertile semen donors.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm agglutination,
      immunofluorescence localization, and flow cytometric analysis of surface
      expression of A36 antigens. Antigen analysis by Western immunoblotting.
      RESULT(S): Monoclonal antibody A36 induced intensive head-to-head, tail-to-tail,
      and head-to-tail agglutination of motile human spermatozoa. Antigens recognized
      by A36 were localized on the acrosomal cap and in the principal tail regions of
      motile, noncapacitated human sperm. Changes in subcellular levels and
      localization of the A36-recognized epitope occurred after capacitation and
      acrosomal loss. A36 reacted with a polymorphic series of proteins in Western
      blots of sperm extracts from humans and various other animal species, including
      mouse testis extracts. A common 53-kd antigen was recognized by the antibody in
      the different antigenic preparations. CONCLUSION(S): A mouse antibody to human
      sperm, monoclonal antibody A36, caused intensive agglutination of noncapacitated
      human spermatozoa and reacted with antigens on the acrosomal cap and in the
      principal tail regions. Of the multiple polypeptides that were reactive with the
      monoclonal antibody in sperm extracts from humans and other animal species, a
      common 53-kd antigen was recognized.

PMID- 10065790
TI  - Characterization of aneuploidy rates, protamine levels, ultrastructure, and
      functional ability of round-headed sperm from two siblings and implications for
      intracytoplasmic sperm injection.
AB  - OBJECTIVE: To characterize and contrast protamine levels, chromatin
      decondensation, chromosome aneuploidy rates, and functional ability of round
      headed sperm from two brothers with round-headed sperm syndrome. DESIGN: Analysis
      of semen samples from siblings with round-headed sperm syndrome and comparison
      with semen of fertile donors. SETTING: University school of medicine and
      laboratories. PATIENT(S): Two infertile siblings. MAIN OUTCOME MEASURE(S): Sperm
      aneuploidy rates of chromosomes X, Y, 13, 18, and 21, protamine 1 and 2 (P1-P2)
      ratios, Western blot evaluation of protamines, and chromatin decondensation
      rates. Additional measures include standard semen quality parameters, electron
      microscopy ultrastructure evaluation, analysis of acrosome morphology, and sperm
      penetration rates. RESULT(S): Aneuploidy rates were significantly increased in
      sibling no. 1 but not in sibling no. 2. The levels of P1 and P2 were decreased in
      sibling no. 1, and an unusual level of protamine precursors was present.
      Ultrastructural differences also were observed between the siblings.
      CONCLUSION(S): These data indicate profound differences in sperm from two
      siblings with complete round-headed sperm syndrome. Multigenic defects and/or
      variable expression of the syndrome may be responsible for the syndrome and
      necessitate individual screening of affected individuals because the pattern of
      expression appears highly variable.

PMID- 10065791
TI  - An alternative medicine study of herbal effects on the penetration of zona-free
      hamster oocytes and the integrity of sperm deoxyribonucleic acid.
AB  - OBJECTIVE: To analyze the effects of certain herbs on sperm DNA and on the
      fertilization process. DESIGN: Prospective comparative study. SETTING: Clinical
      and academic research environment. PATIENT(S): Donor sperm specimens.
      INTERVENTION(S): Zona-free hamster oocytes were incubated for 1 hour in saw
      palmetto (Serenoa repens), echinacea purpura, ginkgo biloba, St. John's wort
      (Hypericum perforatum), or control medium before sperm-oocyte interaction. The
      DNA of herb-treated sperm was analyzed with denaturing gradient gel
      electrophoresis. MAIN OUTCOME MEASURE(S): Oocyte penetration and integrity of the
      sperm BRCAI exon 11 gene. RESULT(S): Pretreatment of oocytes with 0.6 mg/mL of
      St. John's wort resulted in zero penetration. A lower concentration (0.06 mg/mL)
      had no effect. High concentrations of echinacea and ginkgo also resulted in
      reduced oocyte penetration. Exposure of sperm to echinacea purpura and St. John's
      wort resulted in DNA denaturation. In contrast, saw palmetto and ginkgo had no
      effect. Sperm exposed to 0.6 mg/mL of St. John's wort showed mutation of the
      BRCA1 exon 11 gene. CONCLUSION(S): High concentrations of St. John's wort,
      echinacea, and ginkgo had adverse effects on oocytes. Saw palmetto had no effect.
      The data suggested that St. John's wort, ginkgo, and echinacea at high
      concentrations damage reproductive cells. St. John's wort was mutagenic to sperm
      cells.

PMID- 10065792
TI  - Ureaplasma urealyticum in semen: is there any effect on in vitro fertilization
      outcome?
AB  - OBJECTIVE: To determine the effect of the presence of Ureaplasma urealyticum in
      semen on IVF outcome (fertilization, pregnancy, and abortion rates). DESIGN:
      Prospective study. SETTING: Private IVF unit in Athens, Greece. PATIENT(S): One
      hundred ninety-one asymptomatic men with normal semen parameters whose wives
      underwent an IVF cycle. INTERVENTION(S): Culture of semen for U. urealYticum on
      the day of oocyte retrieval. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy,
      and abortion rates after IVF. RESULT(S): Ninety-six (86%) of the 112 women whose
      husbands' semen was negative for U. urealyticum and 65 (82%) of the 79 women
      whose husbands' semen was positive for U. urealyticum underwent ET. The pregnancy
      rate (PR) was 20% (19/96) in the negative group and 17% (11/65) in the positive
      group. An increased incidence of abortions (6/11) was observed in the positive
      group (abortion rate, 54%), compared with 21% (4/19) in the group of women whose
      husbands' semen was negative for U. urealyticum. CONCLUSION(S): Fertilization
      rates and PRs may not be affected by the presence of U. urealyticum in semen on
      the day of oocyte retrieval. It can be presumed that the semen preparation for
      IVF cleanses the semen of U. urealyticum. On the other hand, the higher abortion
      rate in the U. urealyticum-positive group might be related to maternal factors,
      such as an existing U. urealyticum infection or one contracted after conception.

PMID- 10065793
TI  - Expression of P450c17 messenger ribonucleic acid in postmenopausal human ovary
      tissues.
AB  - OBJECTIVE: To investigate the expression of the P450c17 gene in postmenopausal
      human ovaries compared with normal cycling ovaries. DESIGN: Prospective
      nonrandomized clinical research study. SETTING: Servei de Medicina Reproductiva
      and Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall
      d'Hebron, Barcelona, Spain. PATIENT(S): Six premenopausal women and four
      postmenopausal women undergoing bilateral oophorectomy for nonovarian gynecologic
      disease. INTERVENTION(S): Extraction of 10 mL of peripheral venous blood for
      hormone measurements. Extraction of RNA from surgically removed ovaries for
      Northern blot, ribonuclease protection, and reverse transcriptase polymerase
      chain reaction Southern blot assays. MAIN OUTCOME MEASURE(S): Definition of the
      reproductive cycle state of each patient and determination of the level of
      P450c17 gene expression in all samples with the use of the semiquantitative
      reverse transcriptase polymerase chain reaction Southern blot assay. RESULT(S):
      P450c17 messenger RNA levels in postmenopausal ovaries varied considerably
      between samples. Although the levels were similar to those detected in the early
      follicular phase, one of the samples had levels as high as those observed in the
      late follicular phase. CONCLUSION(S): Although the degree varied from one sample
      to another, all the postmenopausal ovaries studied expressed the P450c17 gene at
      the messenger RNA level. In a sample from a patient with endometrial
      adenocarcinoma, the level was as high as the levels observed in the late
      follicular phase.

PMID- 10065794
TI  - Monitoring of hormone replacement therapy in postmenopausal women by transvaginal
      sonography and color flow doppler: study in different phases of sequential
      therapy.
AB  - OBJECTIVE: To assess uterine artery blood flow and endometrial thickness in
      postmenopausal patients receiving sequential hormone replacement therapy (HRT) at
      different phases of the treatment. DESIGN: Prospective controlled study. SETTING:
      Ultrasound and menopause units of the obstetrics and gynecology department of the
      University of Tor Vergata, Rome, Italy. PATIENT(S): Forty postmenopausal women
      were treated with cyclic sequential HRT (transdermal E2, 50 microg/d, days 1-21;
      and dydrogesterone, 10 mg/d, days 12-24). INTERVENTION(S): All patients underwent
      transvaginal color Doppler sonography in the estrogen (phase E) and progestogen
      (phase E/P) phases and after uterine bleeding when no hormone was administered
      (phase 0). MAIN OUTCOME MEASURE(S): Endometrial thickness; systolic, diastolic,
      and mean velocities; and pulsatility and resistance indices of the uterine
      arteries. RESULT(S): No statistically significant difference in endometrial
      thickness between phase E (6.5+/-1.6 mm) and phase E/P (6.0+/-1.7 mm) was
      observed. In phase 0, compared with phases E and E/P, a statistically significant
      decrease in endometrial thickness was found (4.1+/-1.2 mm). Doppler flow
      impedance parameters of uterine arteries during the different phases of the HRT
      cycle showed no differences between the phases considered. CONCLUSION(S): The
      decrease in endometrial thickness in phase 0 suggests a protective effect of our
      cyclic sequential regimen on the endometrium. Dydrogesterone does not interfere
      markedly with the vasodilatory effect of estrogen on uterine arteries.

PMID- 10065795
TI  - Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using
      oral contraceptive ovarian suppression followed by repeat CC treatment.
AB  - OBJECTIVE: To evaluate the effectiveness of a 2-month oral contraceptive (OC)
      ovarian suppression followed by clomiphene citrate (CC) in patients who had
      failed to ovulate on maximum doses of CC alone. DESIGN: Prospective,
      nonrandomized observational study. SETTING: Private tertiary infertility center.
      PATIENT(S): Thirty-eight patients with documented anovulation by transvaginal
      ultrasound follicular monitoring while receiving CC in doses of 150 mg or higher.
      INTERVENTION(S): Two-month ovarian-hypothalamic-pituitary axis suppression with
      OCs followed by repeat CC 100 mg for 5 days. MAIN OUTCOME MEASURE(S): Follicle
      growth, endometrial development, and ovulation were confirmed by transvaginal
      ultrasound. Pregnancy was confirmed by serum hCG levels and 7-week gestation
      ultrasound. RESULT(S): Thirty-eight patients completed 95 treatment cycles.
      Twenty-nine patients became ovulatory (76%), and 69 of the 95 cycles were
      ovulatory (72.6%), resulting in 22 pregnancies in the 38 patients for a
      cumulative pregnancy rate of 58%. CONCLUSION(S): Suppression of the hypothalamic
      pituitary-ovarian axis for 2 months with OCs followed by CC treatment results in
      excellent rates of ovulation and pregnancy in women who had previously failed to
      ovulate on CC alone. This treatment offers an effective, reasonable, inexpensive,
      and low-risk alternative before gonadotropin therapy.

PMID- 10065796
TI  - Advanced semen analysis: a simple screening test to predict intrauterine
      insemination success.
AB  - OBJECTIVE: To determine if a simple screening test of sperm recovery through a
      density gradient preparation and sperm survival after a 24-hour incubation is
      predictive of IUI success. DESIGN: Prospective nonrandomized descriptive study.
      SETTING: Tertiary assisted reproductive technology center. PATIENT(S): Four
      hundred fourteen couples undergoing IUI for male factor and unexplained
      infertility. INTERVENTION(S): An advanced semen analysis, which consisted of a
      basic semen analysis, sperm processing through a density gradient preparation,
      and a 24-hour sperm incubation, was performed on all couples before beginning
      IUIs. MAIN OUTCOME MEASURE(S): Cumulative and per cycle pregnancy rates (PRs)
      were calculated for routine semen parameters, number of sperm processed through
      density gradient, and percent motile sperm after a 24-hour incubation. RESULT(S):
      None of the basic semen analysis parameters accurately predicted IUI success.
      When the processed total motile sperm available for insemination was > or = 10 x
      10(6) and their 24-hour survival was > or = 70%, 89% (162 of 182) of couples
      achieved a pregnancy with a 21.4% (162 of 757) per cycle PR compared to a 2.8%
      (11 of 403) per cycle PR and 4.7% total PR when survival was <70%. With use of
      these cutoff values for the advanced semen analysis, the test had a sensitivity
      of 94% and specificity of 86%. CONCLUSION(S): The number of motile sperm
      available for insemination and especially their 24-hour survival are highly
      predictive of IUI success. This advanced semen analysis is an excellent screening
      test to evaluate couples considering IUI.

PMID- 10065797
TI  - Testis sperm extraction and intracytoplasmic sperm injection guided by prior fine
      needle aspiration mapping in patients with nonobstructive azoospermia.
AB  - OBJECTIVE: To evaluate intracytoplasmic sperm injection (ICSI) outcomes in a
      cohort of men with nonobstructive azoospermia who underwent prior fine-needle
      aspiration (FNA) "maps" to localize sperm and guide testis sperm extraction
      (TESE). DESIGN: Retrospective clinical study. SETTING: University-based
      infertility practice. PATIENT(S): A consecutive cohort of 19 infertile,
      azoospermic men. INTERVENTION(S): Couples underwent IVF-ET in which TESE
      procedures were informed and directed by prior FNA maps of the testis. MAIN
      OUTCOME MEASURE(S): Sperm retrieval and pregnancy rates. RESULT(S): In 21 IVF-ET
      and ICSI cycles, sufficient sperm for all oocytes were retrieved in 20 TESE
      attempts (95%). A mean of 3.1 biopsies per patient were required, with an average
      size of 72 mg. Mean operative time for the TESE procedure was 88 minutes.
      Overall, the two-pronuclear fertilization rate was 66%; ongoing clinical
      pregnancies were obtained in 10 of 21 initiated cycles (48%). CONCLUSION(S): In
      an effort to reduce IVF-ET cancellation rates in cases of nonobstructive
      azoospermia, diagnostic testis FNA can define those patients who are good
      candidates for TESE. It also directs sperm retrieval and minimizes tissue removal
      from nonobstructed testes.

PMID- 10065798
TI  - Thyroid antibody titer and avidity in patients with recurrent miscarriage.
AB  - OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase
      antibody differs between pregnant women in their first trimester who have a
      history of recurrent miscarriage and whose pregnancies continue to term and those
      whose pregnancies fail again later in the first trimester. DESIGN: Controlled
      clinical study. SETTING: Healthy volunteers in an academic research environment.
      PATIENT(S): Pregnant women in their first trimester who had a history of
      recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive
      for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients
      received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody
      titer and avidity (i.e., the net binding strength between antibody and antigen).
      RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and
      avidity was significantly higher in those women who later miscarried compared
      with those whose pregnancies continued. In those whose pregnancies continued to
      term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S):
      Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who
      had had recurrent miscarriages, there appeared to be differences in the humoral
      response to the pregnancy between those whose pregnancies continued to term and
      those whose pregnancies failed again.

PMID- 10065799
TI  - Increased angiotensin-converting enzyme activity in a patient with severe ovarian
      hyperstimulation syndrome.
AB  - OBJECTIVE: To assess plasma angiotensin-converting enzyme (ACE) activity in a
      patient with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Case
      report. SETTING: Private, university-affiliated infertility practice. PATIENT(S):
      A 35-year-old woman with OHSS. INTERVENTION(S): Clomiphene citrate induction of
      ovulation. MAIN OUTCOME MEASURE(S): Plasma ACE activity. RESULT(S): The patient
      had a brain stem infarction as a result of thrombosis caused by severe OHSS.
      Plasma ACE activity was significantly elevated and persisted long after
      resolution of the OHSS. CONCLUSION(S): Elevated ACE activity appears to have been
      associated with the development of OHSS in this patient. Further study of the
      ovarian renin-angiotensin system in the development of OHSS is warranted.

PMID- 10065800
TI  - Testicular sperm aspiration and intracytoplasmic sperm injection for persistent
      infection of the ejaculate.
AB  - OBJECTIVE: To report the successful use of testicular sperm aspiration and
      intracytoplasmic sperm injection in the presence of an Escherichia coli-infected
      ejaculate that previously caused repeated embryo degeneration. DESIGN: Case
      report. SETTING: University medical center. PATIENT(S): A 38-year-old woman who
      did not conceive for 6 years with repeated IVF attempts. Escherichia coli was
      isolated from both the oocyte culture dish and her male partner's ejaculate.
      INTERVENTION(S): Testicular sperm aspiration and intracytoplasmic sperm injection
      followed by ET. MAIN OUTCOME MEASURE(S): Clinical outcome. RESULT(S):
      Establishment of a pregnancy delivered at term. CONCLUSION(S): Patients
      undergoing IVF treatment who have repeated embryo degeneration caused by
      bacterial infection originating in the ejaculate may be treated successfully with
      testicular sperm aspiration and intracytoplasmic sperm injection.

PMID- 10065801
TI  - A case of failed oocyte maturation in vivo and in vitro.
AB  - OBJECTIVE: To study a couple for whom all oocytes failed to mature during three
      attempts at IVF/ICSI treatment. Our aims were (a) to promote oocyte maturation in
      vitro and (b) to identify the stage of maturation arrest. DESIGN: Case report.
      SETTING: Infertility treatment center with academic research links. PATIENT(S):
      Couple with unexplained infertility. INTERVENTION(S): Exogenous gonadotropin
      stimulation culminating in the retrieval of eight oocyte-cumulus complexes that
      were exposed to gonadotropins for 24 hours in vitro. MAIN OUTCOME MEASURE(S):
      Observation of oocyte cumulus complexes, measurements of oocyte diameter, oocyte
      chromatin staining with Hoechst 33258. RESULT(S): The cumulus complexes varied in
      appearance and expanded in vitro, but yielded immature oocytes. Germinal vesicle
      breakdown occurred in all oocytes and chromatin was consistent with arrest at
      entry into M-phase. The oocytes were of a size normally competent to mature.
      CONCLUSION(S): Infertility in this couple was attributed to the failure of
      oocytes to enter M-phase. This was not overcome by exposure to gonadotropins in
      vitro nor associated with incompetence due to small oocyte size.

PMID- 10065802
TI  - Laparoscopic myomectomy and pregnancy outcome in infertile patients.
AB  - OBJECTIVE: To assess outcomes and pregnancy-related complications after
      laparoscopic myomectomy in infertile patients. DESIGN: Retrospective analysis.
      SETTING: Tertiary care advanced laparoscopic center. PATIENT(S): Twenty-eight
      infertile patients with at least one uterine leiomyoma of >5 cm in diameter.
      INTERVENTION(S): Laparoscopic myomectomy. MAIN OUTCOME MEASURE(S): Occurrence of
      pregnancy, delivery rate, and pregnancy-related complications. RESULT(S): The
      average size of the myomas removed was 6 cm (range, 4-13.3 cm). None of the
      procedures were converted to laparotomy. The postoperative rate of intrauterine
      pregnancy was 64.3% (n = 18), including 1 of 2 patients who underwent concomitant
      hysteroscopic myomectomy. Four patients had spontaneous abortions and 14
      delivered viable term neonates. Six women had a vaginal delivery without
      complications and 8 had a cesarean section. No antepartum or intrapartum
      complications were reported. CONCLUSION(S): Laparoscopic myomectomy can be
      offered to patients who want to have children and who refuse to undergo an
      abdominal myomectomy. Patient selection as well as meticulous surgical technique
      are the key factors in achieving a successful outcome.

PMID- 10065803
TI  - Pregnancy following transfer of ooplasm from cryopreserved-thawed donor oocytes
      into recipient oocytes.
AB  - OBJECTIVE: To determine if frozen-thawed donor oocytes could be used to provide
      cytoplasm for transfer into patients' oocytes to improve subsequent embryonic
      development. DESIGN: Prospective evaluation of the procedure in consenting IVF
      patients. SETTING: Assisted reproductive technology program. PATIENT(S): The
      study was open to consenting IVF patients (of any age) with a history of poor
      embryo quality or those couples in which the wife's age was > or = 40 years.
      INTERVENTION(S): Transfer of donor egg cytoplasm from frozen-thawed oocytes into
      the oocytes of infertile recipients. MAIN OUTCOME MEASURE(S): Donor oocyte
      survival following cryopreservation, fertilization following cytoplasmic transfer
      into recipient oocytes, embryo quality, and pregnancy outcome. RESULT(S): Oocytes
      collected from four donors were cryopreserved and 61% (28/46) survived the thaw
      procedure. Cytoplasmic transfer was performed on the eggs of four patients, with
      fertilization occurring in 70.3% (26/37). Twin pregnancy was established in one
      patient (35 years of age) with a history of poor embryo quality. CONCLUSION(S):
      Cryopreserved donor oocytes may provide a source of cytoplasm for transfer into
      recipient oocytes, eliminating the need for cycle synchronization between donor
      and infertile patient.

PMID- 10065804
TI  - Randomized, prospective, single-blind trial of a new parallel technique of Veress
      pneumoperitoneum needle insertion versus the conventional closed method.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of a new closed parallel
      technique of Veress needle insertion and to compare this method with the
      conventional closed approach. DESIGN: Sequential, randomized, prospective, single
      blind clinical trial. SETTING: University hospital. PATIENT(S): Women undergoing
      elective diagnostic and/or operative laparoscopy. Subjects (n = 200) were
      assigned randomly to undergo the conventional closed method (group 1; n = 100) or
      the new parallel technique (group 2; n = 100) of Veress needle insertion.
      INTERVENTION(S): Randomization of the patients was performed in the operating
      room. The investigator performed both diagnostic and operative laparoscopy in
      both study groups. MAIN OUTCOME MEASURE(S): Safety and effectiveness of the
      needle insertion technique. RESULT(S): There were no significant differences in
      demographics between the groups, or in the time required for Veress needle
      insertion to establish pneumoperitoneum. There were no nonlethal major or minor
      intraoperative complications associated with either laparoscopic approach.
      CONCLUSION(S): There is no significant disadvantage to the parallel technique of
      Veress pneumoperitoneum needle insertion compared with the conventional closed
      approach. This new technique avoids the anatomic location of large vessels during
      insertion and may serve as a safeguard to decrease the potential for lethal
      laceration of a major vessel.

PMID- 10065805
TI  - Low and high responders--at what levels of serum estradiol do things start to get
      fuzzy?

PMID- 10065806
TI  - Low and high responders--at what levels of serum estradiol do things start to get
      fuzzy?

PMID- 10065807
TI  - Noninvasive treatment of heterotopic pregnancy?

PMID- 10065808
TI  - Longitudinal analysis of the impact of a level 1 trauma center designation at a
      university hospital.
AB  - BACKGROUND: There have been no quantitative, longitudinal studies on the effect
      of Level 1 Trauma Center (TC) designation on a facility. The purpose of this
      study was to evaluate the impact of such designation. STUDY DESIGN: In September
      1990, a 416-bed core affiliate hospital of the state medical school system was
      state-designated as the Level 1 TC for 6 counties. Data collected from five
      concurrent 1-year periods after TC designation included case number and acuity of
      condition, length of hospital and ICU stays, preventable death rates, financial
      coverage, and neurosurgery and orthopaedic volume. No registry data were
      available before TC designation. RESULTS: While the yearly number of cases
      remained stable, the overall severity of cases increased coincident with a 50%
      reduction in overtriage. The need for ICU services increased over 50%. Mean
      Injury Severity Score increased from 11.0 in year 1 to 13.8 in year 5. There was
      a 25% to 30% increase in severe neurosurgery injuries and in major orthopaedic
      trauma. There was no change in the "self-pay" financial category (12% to 16%) or
      the ratio of blunt to penetrating trauma (90:10). CONCLUSIONS: With Level 1 TC
      designation in a noninner city setting, planners can expect a shift to more
      severely injured patients, but should not expect an increase in nonpaying
      patients. Increases in severe injuries will continue to place strain on the ICU.
      Impact on neurosurgeons and orthopaedic surgeons mandates their support in TC
      planning.

PMID- 10065809
TI  - Cost and morbidity associated with antibiotic prophylaxis in the ICU.
AB  - BACKGROUND: Although the high cost and inappropriate use of antibiotics have been
      documented before, we are not aware of any data on nonsurgical site infectious
      morbidity associated with prolonged courses of prophylactic antibiotics (PA).
      STUDY DESIGN: Data regarding antibiotic orders were collected using a custom
      designed microbiology database in the Surgical Intensive Care Unit of a teaching
      hospital from October 1, 1995 through April 30, 1997. The database was
      retrospectively reviewed. The cost of PA in excess of 1 day was calculated.
      Frequency of bacteremia and line infections were compared in patients receiving 1
      day or less of PA versus more than 4 days of PA. RESULTS: Sixty-one percent of PA
      orders were continued for more than 1 day. Cost of PA beyond 1 day totaled
      $44,893. Bacteremia and line infection were more frequent in the patients
      receiving more than 4 days of PA. CONCLUSIONS: There was poor compliance with the
      protocol of stopping PA at 24 hours. The cost of noncompliance was $44,893. There
      were more bacteremias and line infections in patients with duration of PA of more
      than 4 days.

PMID- 10065810
TI  - Does hoarseness of voice from recurrent nerve paralysis after esophagectomy for
      carcinoma influence patient quality of life?
AB  - BACKGROUND: Recurrent laryngeal nerve injury caused by esophageal cancer surgery
      is worrisome but often temporary; it is unclear when and how the paralysis is
      resolved. Hoarseness of voice from vocal cord paralysis (VCP) can have
      detrimental effects on postoperative patients. The aims of this study were to
      clarify the progress of nerve paralysis related to difficulty in talking after
      surgery and to assess whether hoarseness influences patient quality of life.
      STUDY DESIGN: Between 1985 and 1996, 141 esophageal cancer patients undergoing a
      resection by the Akiyama procedure were cancer free 1 year after surgery. Among
      them, 51 patients with VCP on discharge from the hospital were retrospectively
      reviewed. Their VCPs, body weights, and pulmonary functions were examined yearly.
      They were given a questionnaire relating to the difficulty in talking 1 year
      after surgery. RESULTS: VCP on discharge spontaneously healed within 1 year of
      surgery in 21 patients (41.2%), with the mean duration of difficulty in talking
      5.7 months. The remaining 30 patients had persistent VCP 1 year after surgery; 4
      VCPs spontaneously healed approximately 2 years after surgery. Eleven of the 30
      patients with persistent VCP, who complained of severe hoarseness at 1 year
      postoperatively from inability to close the glottis during exertion, showed
      debilitation in performance status, abilities to go up stairs, and swallowing. In
      the group of patients with severe hoarseness, the percentage of ideal body weight
      (90.6%+/-11.0%) preoperatively and pulmonary functions at 3 years postoperatively
      were deteriorated, resulting in 3 patients with repeated aspiration pneumonia.
      CONCLUSIONS: The inability to compensate for aspiration, presenting as severe
      hoarseness, may be dependent on the preoperative nutritional state of patients
      along with degree of vocal cord atrophy and a decrease in pulmonary support.
      Persistent nerve paralysis deteriorates quality of life until it is adequately
      treated.

PMID- 10065811
TI  - Age at presentation of African-American and Caucasian breast cancer patients.
AB  - BACKGROUND: The purpose of this study was to compare the age at presentation of
      Black-American (Caribbean-American and African-American) and Caucasian breast
      cancer patients. STUDY DESIGN: We reviewed the records of all breast cancer
      patients seen at King's County Hospital Center and SUNY Health Science Center at
      Brooklyn between 1982 and 1995. The patients were stratified based on ethnicity.
      Age distribution, median, and mean ages are compared for Black-American and
      Caucasian patients. RESULTS: The median age, mean age, and standard deviation for
      1,632 African-American patients was 54, 54.17, and 13.11 years, respectively,
      whereas for 671 Caucasians patients it was 62, 60.35, and 13.85 years,
      respectively. Using the Student's t-test for equality of means there is a
      statistically significant difference in the mean age of presentation for the 2
      ethnic groups with a p < 0.001 and a 95% confidence interval for difference
      (4.960, 7.405). More than one-third (37.7%) of Black-American breast cancer
      patients present younger than 50 years of age compared with 24.7% for Caucasians.
      CONCLUSIONS: The younger age at presentation of Black-American breast cancer
      patients ought to be considered while setting screening guidelines for that group
      of women.

PMID- 10065812
TI  - Prognosis of thick cutaneous melanoma.
AB  - BACKGROUND: Ten percent of all patients with melanoma present with thick primary
      tumors (> or = 4 mm or Clark level V). To determine factors associated with
      outcomes, we performed a retrospective analysis of 120 patients who had
      definitive primary treatment of their thick cutaneous melanomas at Memorial Sloan
      Kettering Cancer Center between January 1986 and April 1995. STUDY DESIGN: Data
      were collected via chart review and patient interview. Association between
      factors was determined by chi-square analysis. Survival analysis was performed by
      the method of Kaplan and Meier. Univariate analysis by log-rank testing and
      multivariate analysis using the Cox regression model were used to identify
      factors associated with disease-free and overall survival. RESULTS: Median age
      was 61 years (range 19 to 87 years). There were 80 males and 40 females. Median
      Breslow thickness was 6 mm (range 1.8 to 25.0 mm). Ninety-three patients (78%)
      underwent lymphadenectomy (52 elective and 41 therapeutic). Twenty-one percent
      (11 of 52) of the elective dissections were positive. Median followup was 3.8
      years (5.2 years for patients no evident disease and 2.0 years for those dead of
      disease). Overall survival for the entire group was 62% at 5 years and 43% at 10
      years. Age, gender, and anatomic site (axial versus extremity) were not factors
      predictive of overall survival. Increasing thickness, nodal status at
      presentation (American Joint Commission on Cancer stage II versus III), and the
      presence of ulceration were significant predictors of both disease relapse and
      disease-specific mortality in both univariate and multivariate analyses. There
      was no difference in postrelapse survival between patients suffering local,
      nodal, or distant relapse (p = 0.63). CONCLUSIONS: Patients presenting with thick
      cutaneous melanomas are expected to have more than 50% 5-year survival, and they
      should not be denied the opportunity for aggressive locoregional management.
      Thickness, positive nodal status, and ulceration are associated with a higher
      mortality rate. The fact that patients with local or nodal recurrences fare as
      poorly as those with overt distant metastases implies that the former events are
      predictors of subclinical systemic disease.

PMID- 10065813
TI  - Limitation in gamma probe localization of the sentinel node in breast cancer
      patients with large excisional biopsy.
AB  - BACKGROUND: Radiolocalization and selective biopsy of the sentinel node to
      correctly predict the status of remaining lymph nodes may provide an alternative
      to axillary dissection in selected breast cancer patients with clinically
      negative lymph nodes. STUDY DESIGN: In a nonrandomized, multicenter clinical
      trial, gamma probe localization for lymphatic mapping and sentinel node biopsy
      along with axillary dissection was performed on 75 patients with invasive breast
      cancer and clinically negative lymph nodes. The accuracy of the sentinel node
      biopsy to correctly predict the status of the remaining axillary lymph nodes was
      established through standard pathologic investigation. RESULTS: A sentinel node
      was identified in 70 of 75 patients with a technical success rate of 93%. Of
      these 70 patients, 21 (30%) had axillary nodal metastases identified
      pathologically. Four of these 21 (19%) had sentinel nodes negative for
      metastases. All 4 false-negative patients had prior excisional biopsies. The
      false-negative group had a larger mean maximal biopsy dimension than the true
      positive group. Eleven of the 21 patients with axillary metastases had a
      diagnosis made by core needle biopsy with no false negatives. CONCLUSIONS: The
      accuracy of the sentinel node biopsy in correctly predicting the status of
      remaining axillary lymph nodes may be limited in patients with large excision
      before radiolocalization of the sentinel node. Our findings suggest that
      excisional biopsy should be avoided prior to lymphatic mapping for sentinel node
      biopsy.

PMID- 10065814
TI  - Is there a role of preservation of the spleen in distal pancreatectomy?
AB  - BACKGROUND: The spleen may be preserved during distal pancreatectomy (DP) for
      benign disease. The aim of this retrospective study was to compare the
      postoperative course of DP with or without splenectomy. STUDY DESIGN: From June
      1992 to June 1997, 40 adult patients without chronic pancreatitis underwent
      elective DP for benign lesions. Fifteen underwent spleen-preserving DP
      (Conservative Group) and 25 DP with splenectomy (Splenectomy Group). In spleen
      preserving DP, we attempted to preserve the splenic artery and vein. RESULTS:
      Spleen-preserving DP was successfully performed in all 15 cases. Patient groups
      were comparable for clinical features, indication for DP, and surgical procedure.
      There were no postoperative deaths. The overall incidence of pancreatic fistula
      was 23%, but was significantly higher in the Conservative Group (40%) than in the
      Splenectomy Group (12%; p < 0.05). Subphrenic abscesses were more frequently
      observed in the Conservative Group than in the Splenectomy Group (p < 0.05). The
      mean duration of postoperative hospital stay was 19 days (range 6 to 46 days) in
      the Conservative Group and 12.5 days (range 7 to 45 days) in the Splenectomy
      Group (p < 0.05). At the end of mean followup of 30 months (range 8 to 40
      months), no severe postsplenectomy sepsis was observed in the Splenectomy Group.
      CONCLUSIONS: In our experience, DP with splenectomy has a lower morbidity rate
      and we consider it to be the best procedure for benign pancreatic disease.

PMID- 10065815
TI  - Upper jejunal motility after pancreatoduodenectomy according to the type of
      anastomosis, pancreaticojejunal or pancreaticogastric.
AB  - BACKGROUND: The goal of this study was to compare upper jejunal motor patterns
      after Billroth II pancreatoduodenectomy according to the type of pancreatic
      anastomosis (pancreaticojejunostomy [PJA] or pancreaticogastrostomy [PGA]) and
      the presence or absence of postoperative symptoms. STUDY DESIGN: Manometric
      recordings during fasting and after a 750-kcal meal were performed in the
      afferent limb in 12 patients (7 PJA, 5 PGA) and in the efferent limb in 15 other
      patients (7 PJA, 8 PGA) with a postoperative delay of 15+/-6 days and 3.9+/-2.2
      months respectively. Patient data were compared to those of 20 healthy controls.
      RESULTS: During fasting, the 2 main abnormal findings were a higher incidence (p
      < 0.05) and a slower migration velocity (p < 0.01) of incomplete phase III by
      comparison with that recorded in controls. No difference for phase III was
      observed between the 2 surgical procedures regardless of recording site.
      Trimebutine, 100 mg intravenously, induced a phase III in 89% (24 of 27) of the
      patients. Delay of motor response varied from 5 to 10 minutes without difference
      between the recording site; it was less than 2 minutes in 100% of controls.
      Trimebutine-induced phase III showed similar propagation abnormalities to the
      spontaneous phase III. Duration of the fed pattern (p < 0.001) and motor index (p
      < 0.001) were significantly lower than in controls after the meal, in both limbs,
      whatever the type of anastomosis. Differences between the 2 surgical procedures
      were a slower migration velocity of phase III (p < 0.01) and a lower postmeal
      motor index (p < 0.05) in the efferent limb after PJA than after PGA. Nine of 27
      patients were symptomatic. In these 9 patients, mean phase III migration velocity
      was slower (p < 0.001), and mean area under the postprandial curve was higher (p
      < 0.01) than in asymptomatic patients. Propagated clusters of contractions were
      only found in symptomatic patients and in the afferent limb. CONCLUSIONS:
      Pancreatoduodenectomy is associated with significant motor disturbances, mainly
      slower phase III and a reduced fed pattern, in the upper jejunum, at least during
      the first 3 postoperative months. Few motor differences were observed between PGA
      and PJA pancreatic anastomosis. A lesser occurrence of postsurgical motor
      anomalies does not appear to be an argument for preferring PGA to PJA.

PMID- 10065816
TI  - Up-regulation by human recombinant transforming growth factor beta-1 of collagen
      production in cultured dermal fibroblasts is mediated by the inhibition of nitric
      oxide signaling.
AB  - BACKGROUND: Hypertrophic scarring remains the most disabling sequela for burn
      survivors. Little is known about its pathogenesis. Collagen accumulation,
      however, has been consistently observed in burn hypertrophic scars (HS). STUDY
      DESIGN: We have studied collagen production in the dermal fibroblasts derived
      from HS, which has developed for 9 months to 2 years. Reconstructive surgery was
      performed to remove HS from which the fibroblasts were cultured. Similarly, the
      normal cells were grown from the patient's donor site (DS), which provided
      autografting to the HS site. Collagen production in HS and DS fibroblasts was
      compared and analyzed in minimal essential amino acid medium containing 5% fetal
      bovine serum with inclusion of L-ascorbic acid (100 microg/mL) and beta
      aminopropoinitrile (100 microg/mL) by monitoring a 20-h [3H]proline incorporation
      into bacterial collagenase III-digestible protein in the conditioned media.
      RESULTS: We failed to detect any significant difference in collagen production in
      vitro between HS and DS. Irrespective of the fibroblasts from HS or DS, collagen
      production was substantially stimulated by human recombinant transforming growth
      factor beta-1 (TGF-beta1) (20 ng/mL) by approximately 250% after a 3-day
      pretreatment. In contrast, sodium nitroprusside (SNP) at 100 microM exhibited
      significant suppression (68%), which was rescued by hemoglobin (10 microM). TGF
      beta1 significantly decreased nitric oxide (NO) production by 55%. In contrast,
      NO level drastically increased by 350% following SNP treatment. Epidermal growth
      factor showed no effect on either collagen production or NO level. The linear
      regression analysis shows a significant inverse correlation (r = 0.72; p < 0.05)
      of NO level with collagen production, suggesting the involvement of NO signaling
      in the modulation of collagen production. Consistent with the notion, we further
      showed that N-nitro-L-arginine methyl ester (100 microM) caused a synergistic
      stimulation and an arrested inhibition of collagen production in the presence of
      TGFbeta-1 and SNP, respectively. 8-BrcGMP (300 microM) mimicked the NO inhibitory
      action, while methylene blue (50 microM) restored the collagen production which
      was inhibited by SNP. Moreover, 8-BrcGMP offset the stimulation of collagen
      production. CONCLUSIONS: The dermal fibroblasts derived from HS were not
      different from normals with respect to collagen production and their responses to
      regulations. The inhibition of collagen production was achieved by a cGMP
      dependent NO action. TGFbeta-1 inhibited NO/cGMP signaling to ensure its
      stimulatory effect on collagen production in the dermal fibroblasts.

PMID- 10065817
TI  - Omentoplasty in the prevention of deep abdominal complications after surgery for
      hydatid disease of the liver: a multicenter, prospective, randomized trial.
      French Associations for Surgical Research.
AB  - BACKGROUND: Omentoplasty (OP) is thought to fill residual cavity, to assist
      healing of raw surfaces, and to promote resorption of serosal fluid and
      macrophagic migration in septic foci. Results published to date, whether
      retrospective or prospective, are not controlled and are discordant. STUDY
      DESIGN: The authors investigated whether OP, either filling the residual cavity
      after unroofing, or covering the hepatic raw surface after pericystectomy, could
      reduce the rate or severity of deep abdominal complications (DAC) after surgical
      treatment of hydatid disease of the liver. Between January 1993 and December
      1996, 115 consecutive patients (51 males and 64 females, mean age 42+/-16 years
      [range 10 to 80 years]) with previously unoperated uni- or multilocular hydatid
      disease of the liver, complicated or not, without other abdominal hydatid
      disease, were randomly allotted to OP (n = 58) or not (NO) (n = 57) after
      unroofing, total, or partial pericystectomy. Patients were divided into 2 strata
      according to the site of the cyst with respect to the diaphragm: a)
      posterosuperior segments II, VII, and VIII or b) anterior segments III, IV, V,
      and VI. Main outcomes measures included deep bleeding, hematoma, infection, or
      bile leakage. Subsidiary measures included wound complications, extraabdominal
      complications, duration of operation, and length of hospital stay. RESULTS: Both
      groups were comparable regarding patient demographics, cyst characteristics,
      intraoperative procedures, search for bile leaks, and intraoperative transfusion
      requirements. On the other hand, more patients (86%) in NO had associated
      drainage of the abdominal cavity than in OP (64%) and the duration of operation
      was 9 minutes longer in OP, but neither of these differences was statistically
      significant. Less DAC occurred in OP (10%) than in NO (23%) (a posteriori gamma
      risk < 0.05) and fewer deep abdominal abscesses (0 versus 11%) (p < 0.03). Median
      duration of hospital stay, however, was similar. CONCLUSIONS: OP decreases the
      rate of DAC and especially deep abdominal abscess after surgical treatment
      (unroofing or pericystectomy) for hydatid disease of the liver and should be
      recommended in this setting.

PMID- 10065818
TI  - Penetrating injuries to the subclavian and axillary vessels.
AB  - BACKGROUND: Subclavian and axillary vascular injuries are notorious for their
      mortality and their difficult surgical exposure. In the present study we analyze
      our experience with 79 patients and describe the techniques used for surgical
      access to these vessels. STUDY DESIGN: Retrospective review of the medical
      records of all patients with penetrating injuries to the subclavian or axillary
      vessels who had been admitted to 2 Los Angeles trauma centers during a 4-year, 3
      month period. RESULTS: Seventy-nine patients were admitted during the study
      period January 1993 to March 1997 (58 gunshot injuries, 21 other penetrating
      injuries). The artery was injured in 59 patients and the vein in 40 (20 patients
      had both arterial and venous injuries). Eighteen patients (23%) were admitted
      with no signs of life or were in extremis and underwent an emergency room
      thoracotomy without any survivors. Fifty-eight patients underwent exploration in
      the operating room, 1 patient with an arteriovenous subclavian fistula was
      successfully managed with a radiologically placed endovascular stent, and 2
      patients with minimal subclavian artery injuries were managed nonoperatively.
      Overall mortality was 34.2%. Excluding the ER thoracotomies the overall mortality
      was 14.8%. The mortality for isolated arterial injuries was 20.5%, for isolated
      venous injuries 50%, and for both vessels 45.0%. The mortality in venous injuries
      was significantly higher than in arterial injuries (p < 0.05). The standard
      clavicular incision provided adequate exposure in 32 (50.0%) of the operating
      room cases. In the other 50% of operating room cases a combination of a
      clavicular incision with a median sternotomy or thoracotomy was necessary.
      Proximal subclavian injuries may be accessed through a clavicular incision
      combined with a median sternotomy irrespective of left or right site location.
      CONCLUSIONS: Subclavian and axillary vascular injuries remain lethal. A
      clavicular incision provides satisfactory surgical exposure in about half the
      patients. In patients with proximal injuries addition of a median sternotomy
      provides adequate surgical access in both right and left subclavian vessels.

PMID- 10065819
TI  - Results and prognostic factors in stage I(E)-II(E) primary gastric lymphoma after
      gastrectomy.
AB  - BACKGROUND: Infrequency of gastric lymphomas and lack of homogeneity of studies
      dealing with them preclude accurate management schemes. Helicobacter pylori (HP)
      and Isaacson's classification are new factors to consider. Our aim was to analyze
      these and other prognostic factors in a homogeneous series. STUDY DESIGN: Fifty
      four patients (mean age 62.4 years) treated by gastrectomy for primary gastric
      non-Hodgkin's lymphoma in stages IE or IIE were retrospectively reviewed. Twenty
      seven patients received postoperative chemotherapy. HP and histologic features
      were studied using new slides from the paraffin-embedded gastrectomy specimens.
      RESULTS: Postoperative morbidity and mortality rates were 19% and 5.6%,
      respectively. Five-year survival was 83%. Classification showed low-grade tumors
      in 59% and high-grade tumors in 41%. HP was positive in 64% of the patients. A
      poorer survival was associated with high-grade tumors (p = 0.02) and serosa
      involvement (p = 0.02). We did not find any significant difference between
      patients treated either by partial or total gastrectomy (p = 0.2), or receiving
      chemotherapy or not (p = 0.9). Nor did we appreciate any differences concerning
      margin involvement (p = 0.9). CONCLUSIONS: Most primary gastric lymphoma patients
      have gastric HP. Serosa involvement and high-grade tumors adversely influence
      survival but gastrectomy type, resection margin invasion, and postoperative
      chemotherapy did not appear to have any influence.

PMID- 10065820
TI  - Postoperative liver failure after major hepatic resection for hepatocellular
      carcinoma in the modern era with special reference to remnant liver volume.
AB  - BACKGROUND: Postoperative liver failure is a life-threatening complication after
      hepatic resection. Because of recent advances in liver surgery technique and a
      more stringent patient selection, mortality after hepatic resection has steadily
      decreased, but its incidence still ranges from 10% to 20%. The factors linked to
      postoperative liver failure in major hepatic resection in the modern era should
      be reevaluated. STUDY DESIGN: Of 80 patients with viral markers (hepatitis C
      viral antibody or hepatitis B surface antigen) who underwent major hepatic
      resections (no less than bisegmentectomies) for hepatocellular carcinoma between
      1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6
      months after hepatectomy. The cause of liver failure was analyzed based on both
      the preoperative data and the intraoperative findings. In addition, since all the
      patients who died of liver failure underwent a right hepatic lobectomy, a further
      data analysis was also done in 47 patients who underwent a right lobectomy of the
      liver. A volumetric analysis by CT was then done to evaluate the remnant liver
      volume. RESULTS: Between the patients with liver failure and those without liver
      failure who underwent a right lobectomy, there were no significant differences in
      preoperative data or intraoperative findings. Volumetric analysis revealed that
      the remnant liver volume of patients who died of liver failure was significantly
      smaller than that of patients who lived (p = 0.008). The incidence of liver
      failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of
      20 (38%), while it was 0 of 27 in patients with a liver volume of no less than
      250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in
      patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus
      (p = 0.0072). CONCLUSIONS: The expected remnant liver volume appears to be a good
      predictor for liver failure in patients who undergo a right lobectomy of the
      liver. In patients with diabetes mellitus and an expected remnant liver volume of
      less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient
      selection based on volumetric analysis in major hepatectomy cases could help
      prevent the occurrence of postoperative liver failure.

PMID- 10065821
TI  - Survival among chronic renal failure patients requiring major abdominal surgery.
AB  - BACKGROUND: There is limited literature on survival of patients with chronic
      renal failure (CRF) who require major abdominal surgery. The goal of the present
      study was to evaluate indications for surgery and survival among dialysis
      patients undergoing major abdominal operations. STUDY DESIGN: Medical records for
      26 CRF patients at our institution undergoing major nonvascular abdominal
      operations from 1990 to 1996 were reviewed. Results were evaluated by chi-square
      analysis. RESULTS: Surgery was performed emergently in 21 patients (81%) and
      electively in 5 patients (19%). The most common finding among the emergency
      surgery patients was ischemic colitis, occurring in 9 of 21 patients (43%).
      Postoperative (30-day) mortality among the emergency surgery patients was 38%.
      Longterm (1 year) survival was 28%. All 5 patients undergoing elective surgery
      are alive on followup of 1 to 5 years. The disparity in longterm survival between
      the emergency surgery versus the elective surgery patients was statistically
      significant (p = 0.004). CONCLUSIONS: Emergency surgery in patients with CRF is
      associated with poor survival rates. Colonic ischemia is a significant problem
      among these patients.

PMID- 10065822
TI  - The positive features of trauma center designation.

PMID- 10065823
TI  - How can we increase the number of organ and tissue donors?

PMID- 10065824
TI  - Combined laparoscopic and thoracoscopic approach to esophagectomy.

PMID- 10065825
TI  - Posttraumatic renal failure.

PMID- 10065826
TI  - Elevated arterial base deficit.

PMID- 10065827
TI  - Zuckerkandl's tuberculum.

PMID- 10065828
TI  - Zuckerkandl's tuberculum in thyroid surgery.

PMID- 10065829
TI  - Vascular injuries during laparoscopy associated with the Hasson technique.

PMID- 10065830
TI  - Neural solution to the correction of miss distance in gun fire control system.
AB  - Multilayer perceptrons trained with the backpropagation algorithm are tested in
      gun fire control system for error correction and are compared to optimal
      algorithms based on minimum mean square error. The structure of the proposed
      neural controller is described and performance results are shown.

PMID- 10065831
TI  - Universal distribution of saliencies for pruning in layered neural networks.
AB  - A better understanding of pruning methods based on a ranking of weights according
      to their saliency in a trained network requires further information on the
      statistical properties of such saliencies. We focus on two-layer networks with
      either a linear or nonlinear output unit, and obtain analytic expressions for the
      distribution of saliencies and their logarithms. Our results reveal unexpected
      universal properties of the log-saliency distribution and suggest a novel
      algorithm for saliency-based weight ranking that avoids the numerical cost of
      second derivative evaluations.

PMID- 10065832
TI  - On a recurrent neural network producing oscillations.
AB  - A recurrent two-node neural network producing oscillations is analyzed. The
      network has no true inputs and the outputs from the network exhibit a circular
      phase portrait. The weight configuration of the network is investigated,
      resulting in analytical weight expressions, which are compared with numerical
      weight estimates obtained by training the network on the desired trajectories.
      The values predicted by the analytical expressions agree well with the findings
      from the numerical study, and can also explain the asymptotic properties of the
      networks studied.

PMID- 10065833
TI  - A cascading structure and training method for multilayer neural networks.
AB  - A new structure and training method for multilayer neural networks is presented.
      The proposed method is based on cascade training of subnetworks and optimizing
      weights layer by layer. The training procedure is completed in two steps. First,
      a subnetwork, m inputs and n outputs as the style of training samples, is trained
      using the training samples. Secondly the outputs of the subnetwork is taken as
      the inputs and the outputs of the training sample as the desired outputs, another
      subnetwork with n inputs and n outputs is trained. Finally the two trained
      subnetworks are connected and a trained multilayer neural networks is created.
      The numerical simulation results based on both linear least squares back
      propagation (LSB) and traditional back-propagation (BP) algorithm have
      demonstrated the efficiency of the proposed method.

PMID- 10065834
TI  - Adaptive rival penalized competitive learning and combined linear predictor model
      for financial forecast and investment.
AB  - We propose a prediction model called Rival Penalized Competitive Learning (RPCL)
      and Combined Linear Predictor method (CLP), which involves a set of local linear
      predictors such that a prediction is made by the combination of some activated
      predictors through a gating network (Xu et al., 1994). Furthermore, we present
      its improved variant named Adaptive RPCL-CLP that includes an adaptive learning
      mechanism as well as a data pre-and-post processing scheme. We compare them with
      some existing models by demonstrating their performance on two real-world
      financial time series--a China stock price and an exchange-rate series of US
      Dollar (USD) versus Deutschmark (DEM). Experiments have shown that Adaptive RPCL
      CLP not only outperforms the other approaches with the smallest prediction error
      and training costs, but also brings in considerable high profits in the trading
      simulation of foreign exchange market.

PMID- 10065835
TI  - A survey of partially connected neural networks.
AB  - Almost all artificial neural networks are by default fully connected, which often
      implies a high redundancy and complexity. Little research has been devoted to the
      study of partially connected neural networks, despite its potential advantages
      like reduced training and recall time, improved generalization capabilities,
      reduced hardware requirements, as well as being a step closer to biological
      reality. This publication presents an extensive survey of the various kinds of
      partially connected neural networks, clustered into a clear framework, followed
      by a detailed comparative discussion.

PMID- 10065836
TI  - The prospects for analogue neural VLSI.
AB  - In recent years, the efforts of analogue, neural-hardware designers have shifted
      from generic analogue neurocomputers to "niche" markets in sensor fusion and
      robotics, and we explain why this is so. We describe the main differences between
      digital and analogue computation, and consider the advantages of pure analogue
      and pulsed methods of design. We then investigate some important issues in
      analogue design of neural machines, namely weight storage (volatile and non
      volatile), on-chip learning, and arithmetic accuracy and its relationship to
      noise. Finally, we outline those areas in which analogue techniques are likely to
      prove most useful, and speculate as to their likely long-term utility.

PMID- 10065837
TI  - A neural network method for identification of prokaryotic and eukaryotic signal
      peptides and prediction of their cleavage sites.
AB  - We have developed a new method for the identification of signal peptides and
      their cleavage sites based on neural networks trained on separate sets of
      prokaryotic and eukaryotic sequences. The method performs significantly better
      than previous prediction schemes, and can easily be applied to genome-wide data
      sets. Discrimination between cleaved signal peptides and uncleaved N-terminal
      signal-anchor sequences is also possible, though with lower precision.
      Predictions can be made on a publicly available WWW server:
      http://www.cbs.dtu.dk/services/SignalP/.

PMID- 10065838
TI  - Least-squares methods for blind source separation based on nonlinear PCA.
AB  - In standard blind source separation, one tries to extract unknown source signals
      from their instantaneous linear mixtures by using a minimum of a priori
      information. We have recently shown that certain nonlinear extensions of
      principal component type neural algorithms can be successfully applied to this
      problem. In this paper, we show that a nonlinear PCA criterion can be minimized
      using least-squares approaches, leading to computationally efficient and fast
      converging algorithms. Several versions of this approach are developed and
      studied, some of which can be regarded as neural learning algorithms. A
      connection to the nonlinear PCA subspace rule is also shown. Experimental results
      are given, showing that the least-squares methods usually converge clearly faster
      than stochastic gradient algorithms in blind separation problems.

PMID- 10065839
TI  - Motion planning with complete knowledge using a colored SOM.
AB  - The motion planning problem requires that a collision-free path be determined for
      a robot moving amidst a fixed set of obstacles. Most neural network approaches to
      this problem are for the situation in which only local knowledge about the
      configuration space is available. The main goal of the paper is to show that
      neural networks are also suitable tools in situations with complete knowledge of
      the configuration space. In this paper we present an approach that combines a
      neural network and deterministic techniques. We define a colored version of
      Kohonen's self-organizing map that consists of two different classes of nodes.
      The network is presented with random configurations of the robot and, from this
      information, it constructs a road map of possible motions in the work space. The
      map is a growing network, and different nodes are used to approximate boundaries
      of obstacles and the Voronoi diagram of the obstacles, respectively. In a second
      phase, the positions of the two kinds of nodes are combined to obtain the road
      map. In this way a number of typical problems with small obstacles and passages
      are avoided, and the required number of nodes for a given accuracy is within
      reasonable limits. This road map is searched to find a motion connecting the
      given source and goal configurations of the robot. The algorithm is simple and
      general; the only specific computation that is required is a check for
      intersection of two polygons. We implemented the algorithm for planar robots
      allowing both translation and rotation and experiments show that compared to
      conventional techniques it performs well, even for difficult motion planning
      scenes.

PMID- 10065840
TI  - Two constructive methods for designing compact feedforward networks of threshold
      units.
AB  - We propose two algorithms for constructing and training compact feedforward
      networks of linear threshold units. The SHIFT procedure constructs networks with
      a single hidden layer while the PTI constructs multilayered networks. The
      resulting networks are guaranteed to perform any given task with binary or real
      valued inputs. The various experimental results reported for tasks with binary
      and real-valued inputs indicate that our methods compare favorably with
      alternative procedures deriving from similar strategies, both in terms of size of
      the resulting networks and of their generalization properties.

PMID- 10065841
TI  - Entropic analysis and incremental synthesis of multilayered feedforward neural
      networks.
AB  - Neural network architecture optimization is often a critical issue, particularly
      when VLSI implementation is considered. This paper proposes a new minimization
      method for multilayered feedforward ANNs and an original approach to their
      synthesis, both based on the analysis of the information quantity (entropy)
      flowing through the network. A layer is described as an information filter which
      selects the relevant characteristics until the complete classification is
      performed. The basic incremental synthesis method, including the supervised
      training procedure, is derived to design application-tailored neural paradigms
      with good generalization capability.

PMID- 10065842
TI  - Stochastic ICA contrast maximisation using OJA's nonlinear PCA algorithm.
AB  - Independent Component Analysis (ICA) is an important extension of linear
      Principal Component Analysis (PCA). PCA performs a data transformation to provide
      independence to second order, that is, decorrelation. ICA transforms data to
      provide approximate independence up to and beyond second order yielding
      transformed data with fully factorable probability densities. The linear ICA
      transformation has been applied to the classical statistical signal-processing
      problem of Blind Separation of Sources (BSS), that is, separating unknown
      original source signals from a mixture whose mode of mixing is undetermined. In
      this paper it is shown that Oja's Nonlinear PCA algorithm performs a general
      stochastic online adaptive ICA. This analysis is corroborated with three
      simulations. The first separates unknown mixtures of original natural images,
      which have sub-Gaussian densities, the second separates linear mixtures of
      natural speech whose densities are super-Gaussian. Finally unknown mixtures of
      original images, which have both sub- and super-Gaussian densities are separated.

PMID- 10065843
TI  - The veterinarian's role in enrichment.

PMID- 10065844
TI  - Occupational injuries and illnesses reported by zoo veterinarians in the United
      States.
AB  - A 14-page comprehensive survey was mailed to all 565 United States members of the
      American Association of Zoo Veterinarians to identify the frequency of physical
      injuries, radiation exposures, chemical exposures, allergic or irritant
      reactions, infections, and use of preventive measures, and 315 (55.8%)
      veterinarians responded. Significant findings include major animal-related injury
      (61.5%), back injury (55%), necropsy injury (44.1%), adverse formalin exposure
      (40.2%), animal allergy (32.2%), zoonotic infection (30.2%), and insect allergy
      (14.2%). We also found that gender, length of experience, and practice type
      affected the number and type of incidents encountered in practice. Females
      reported a higher rate of zoonotic infection, insect allergy, and adverse
      exposure to anesthetic gas, formalin, and disinfectants/sterilants. Zoo
      veterinarians with more years of experience were more likely to receive major
      animal-related injury and associated hospitalization, back injury, and lost work
      time associated with back injury. Full-time zoo veterinarians were more likely to
      report back injury and inadequate knowledge of occupational hazards. Results are
      compared with hazards reported by veterinarians working in other fields. The
      frequency of injuries reported demonstrates a greater need for comprehensive
      health and safety programs for zoo veterinarians.

PMID- 10065845
TI  - Ultrasonographic monitoring of artificially stimulated ejaculation in three
      rhinoceros species (Ceratotherium simum, Diceros bicornis, Rhinoceros unicornus).
AB  - Manual massage of the penis and rectal electroejaculation methods have been
      minimally effective for collecting semen from the rhinoceros. These two methods
      for stimulating ejaculation were evaluated by rectal ultrasonography. One
      individual each of three rhinoceros species (Ceratotherium simum simum,
      Rhinoceros unicornis and Diceros bicornis) was stimulated by manual massage of
      the penis and two black rhinoceroses (Diceros bicornis) were electroejaculated.
      On ultrasonography, neither manual massage nor rectal electroejaculation affected
      the accessory glands. The pelvic urethra remained empty during manual massage of
      unconditioned animals; however, this area was filled before commencement of
      massage of conditioned animals. The pelvic urethra also filled during
      electroejaculation. Semen accumulated in the pelvic urethra during pauses between
      electrical stimulations and was moved distally into the penile urethra by rectal
      and penile massage. The volumes of seminal fluid recovered from
      electroejaculation in this study exceeded previously reported attempts. This
      study demonstrated the potential of transrectal imaging for improving the
      recovery of semen by these methods.

PMID- 10065846
TI  - Hematology and chemistry reference values for free-ranging harbor seals (Phoca
      vitulina) and the effects of hemolysis on chemistry values of captive harbor
      seals.
AB  - Most reported laboratory reference values for harbor seals (Phoca vitulina) are
      derived from captive seals, or stranded seals that have recovered from disease in
      marine mammal centers. This study established hematology and serum chemistry
      reference values for free-ranging harbor seals, using methods and that are
      current and readily available, and determined the effects of hemolysis on serum
      chemistry values of captive harbor seals. Blood samples were collected for
      hematologic and serum chemistry measurements from 14 clinically normal, adult
      male and female harbor seals and two juvenile harbor seals (approximate age 6 mo)
      captured in saltwater sloughs and estuaries near Moss Landing, California, USA.
      Values for amylase, globulin, and differential leukocyte count, not previously
      reported, were determined. In general, hematology and chemistry values in adults
      were similar to those reported for free-ranging and captive harbor seals, except
      for glucose, urea nitrogen, and lactate dehydrogenase (LDH) values, which were
      higher than those reported previously. Red blood cell counts in the two juveniles
      were higher than in adults and in young harbor seals studied previously. To
      determine the effects of hemolysis on serum chemistry values, two intensities of
      hemolysis were generated experimentally in blood collected from 11 harbor seals
      recovering from injuries or stranding at the Marine Mammal Center (Sausalito,
      California 94965, USA). Moderate hemolysis (++, 1 g/L hemoglobin, red-tinged)
      significantly increased LDH activity, whereas severe hemolysis ( , 2 g/L
      hemoglobin, cherry red) significantly increased total protein, albumin,
      calculated globulin, LDH, and total bilirubin and significantly decreased
      creatinine. The effects of hemolysis must be considered when chemistry results of
      harbor seals are interpreted.

PMID- 10065847
TI  - Blood chemistry and hematology of gray seal (Halichoerus grypus) pups from birth
      to postweaning.
AB  - Serum and plasma samples were collected from 92 gray seal (Halichoerus grypus)
      pups, all less than 5 wk old, and from 21 yearlings during the breeding season at
      the Isle of May, Firth of Forth, Scotland, for hematologic and clinical chemistry
      analysis. In the pups, total WBC, total protein, and glucose values increased
      until weaning and declined during the postweaning fast. Liver enzymes,
      particularly alkaline phosphatase, were high at birth and decreased steadily with
      age, most rapidly during the postweaning fast. In the yearlings, total WBC,
      erythrocyte sedimentation rates, and rectal temperatures were significantly
      higher than in the pups and glucose levels were significantly lower. Therefore,
      consideration should be given to the growth phase of gray seal pups (lactation or
      postweaning fast) or stage of development when hematology and clinical
      chemistries are used for diagnostic purposes.

PMID- 10065848
TI  - Causes of erroneous white blood cell counts and differentials in clinically
      healthy young northern elephant seals (Mirounga angustirostris).
AB  - From 1993 to 1995, approximately 10% of the clinically healthy northern elephant
      seals (Mirounga angustirostris) at The Marine Mammal Center in California
      exhibited a large unexplained increase in their white blood cell (WBC) count. In
      these animals, WBC counts ranged from 28,780 to 125,000/mm3, with a mean of
      50,087/mm3. Significant correlations between the leukocytosis and weight gain and
      day of admittance were identified, but no correlation existed between
      leukocytosis and general state of health, sex, length of stay, or diet. Bone
      marrow contamination of blood samples, erroneous automated leukocyte counts, and
      leukogram changes consistent with subclinical inflammation were the major factors
      contributing to the elevated WBC counts in these apparently clinically healthy
      animals.

PMID- 10065849
TI  - Abdominal ascites in electric eels (Electrophorus electricus) associated with
      hepatic hemosiderosis and elevated water pH.
AB  - Six electric eels (Electrophorus electricus) from various centers that house
      aquatic organisms presented clinically with abdominal distension following
      prolonged exposure to elevated environmental pH. Postmortem examination revealed
      marked ascites. Culture of the abdominal fluid from three of the eels yielded
      either Aeromonas hydrophila or Citrobacter freundii, which were most likely
      secondary invaders. Histopathology showed marked iron accumulation in both
      hepatocytes and hepatic macrophage aggregates.

PMID- 10065850
TI  - The effects of dietary vitamin C on growth rates of juvenile slider turtles
      (Trachemys scripta elegans).
AB  - Seventeen juvenile red-eared slider turtles (Trachemys scripta elegans) were
      separated into two groups: one group received a diet that included vitamin C
      supplementation, the other group received a similar diet devoid of supplemental
      vitamin C. Overall body mass and carapace length were measured monthly for a
      period of 1 yr. No significant differences were observed between the growth rates
      of the two experimental groups, suggesting that dietary vitamin C is not
      essential for normal growth and development in juvenile red-eared slider turtles.

PMID- 10065851
TI  - Noninvasive monitoring of fetal growth and development in the Siberian polecat
      (Mustela eversmanni).
AB  - The Siberian polecat (Mustela eversmanni) is the preferred species to assess
      procedures and establish normative values for application in the related and
      endangered black-footed ferret (Mustela nigripes). This study was undertaken to
      physically, ultrasonographically, and radiographically evaluate fetal development
      in a spontaneously breeding captive Siberian polecat population.
      Ultrasonographically, fetal sac enlargement allowed presumptive pregnancy
      detection as early as 12 days of gestation, the fetal pole was the first
      definitive sign of pregnancy at about 18 days of gestation, when the fetal heart
      beat also appeared, and definitive pregnancy detection by ultrasound was
      essentially 100% accurate after 18 days. The estimation of fetal number by
      ultrasound was less reliable than by radiography, as it is in other litter
      bearing species. Crown-rump growth, organ differentiation, and calcification
      patterns resembled those of domestic carnivores except that comparable
      developmental stages in polecats occurred at disproportionately later times,
      suggesting that young Siberian polecats are delivered in a less developed state.
      Careful palpation permitted detection of pregnancy after day 17 but with less
      certainty than with ultrasound. Radiographic evaluation was insensitive and of
      limited value for pregnancy detection until near term. Litter number and fetal
      detail were difficult to assess until ossification could be observed, 3-6 days
      before parturition.

PMID- 10065852
TI  - Analysis of urine from free-ranging mountain gorillas (Gorilla gorilla beringei)
      for normal physiologic values.
AB  - Voided urine samples were collected from apparently healthy free-living mountain
      gorillas (Gorilla gorilla beringei) and analyzed for normal physiologic values.
      Mountain gorillas were found to have a high urinary pH (x = 8.45) and low
      specific gravity (x = 1.013). Commercial dipsticks appear to be unreliable for
      the measurement of specific gravity and leukocytes. The establishment of urinary
      reference intervals should aid in the noninvasive detection of certain diseases
      in the mountain gorilla and assist with prompt and effective decisions regarding
      the immobilization and treatment of individual gorillas.

PMID- 10065853
TI  - Serum biochemistry of captive and free-ranging gray wolves (Canis lupus).
AB  - Normal serum biochemistry values are frequently obtained from studies of captive
      sedentary (zoo) or free-ranging (wild) animals. It is frequently assumed that
      values obtained from these two populations are directly referable to each other.
      We tested this assumption using 20 captive gray wolves (Canis lupus) in
      Minnesota, USA, and 11 free-ranging gray wolves in Alaska, USA. Free-ranging
      wolves had significantly (P < 0.05) lower sodium, chloride, and creatinine
      concentrations and significantly higher potassium and blood urea nitrogen (BUN)
      concentrations; BUN to creatinine ratios; and alanine aminotransferase, aspartate
      aminotransferase, and creatine kinase activities relative to captive wolves.
      Corticosteroid-induced alkaline phosphatase activity (a marker of stress in
      domestic dogs) was detected in 3 of 11 free-ranging wolves and in 0 of 20 captive
      wolves (P = 0.037). This study provides clear evidence that serum biochemical
      differences can exist between captive and free-ranging populations of one
      species. Accordingly, evaluation of the health status of an animal should
      incorporate an understanding of the potential confounding effect that nutrition,
      activity level, and environmental stress could have on the factor(s) being
      measured.

PMID- 10065854
TI  - Antibody response of kori bustards (Ardeotis kori) and houbara bustards
      (Chlamydotis undulata) to live and inactivated Newcastle disease vaccines.
AB  - Adult houbara bustards (Chlamydotis undulata) and juvenile kori bustards
      (Ardeotis kori) were given four regimens of commercially available inactivated
      and live poultry paramyxovirus type 1 (PMV-1) vaccines. Immunologic response to
      vaccination was assessed by hemagglutination inhibition assay of serum. Kori
      bustards, to which a dose of 0.5 ml of a commercially available inactivated
      vaccine for poultry had been administered intramuscularly (0.15 ml/kg body
      weight), failed to develop hemagglutinating antibodies, but antibody titers of
      low intensity and duration were detected following administration of a second and
      third subcutaneous dose of 2.0 ml vaccine per bird (0.40-0.45 ml/kg). In
      subsequent trials, when inactivated vaccine was administered subcutaneously at
      1.0 ml/kg body weight following two or four live vaccinations administered by the
      ocular route, juvenile kori bustards developed higher, more persistent titers of
      antibodies. Kori bustards given four live vaccinations followed by inactivated
      vaccine developed higher titers of longer duration compared with kori bustards
      given two live vaccines followed by inactivated vaccine. Antibody titers of kori
      bustards given inactivated vaccine were higher and more persistent than the
      antibody response to live vaccination. Houbara bustards, previously vaccinated
      with inactivated vaccine, that were given a booster dose of inactivated vaccine
      maintained high mean antibody titers (> or = log, 5) for 52 wk. The authors
      recommend that inactivated PMV-1 vaccine should be administered by subcutaneous
      injection of 1.0 ml/kg vaccine to bustards. Adult bustards, previously vaccinated
      with inactivated vaccine, should be vaccinated annually with inactivated vaccine.
      Juvenile bustards should receive a second dose of inactivated vaccine 4-6 mo
      after the first dose of inactivated vaccine. Even though inactivated PMV-1
      vaccines induced hemagglutination inhibition antibodies and produced no adverse
      reactions, further studies will be required to determine the protective efficacy
      of the antibody.

PMID- 10065855
TI  - Bronchoscopic and serologic diagnosis of Aspergillus fumigatus pulmonary
      infection in a bottlenose dolphin (Tursiops truncatus).
AB  - A 4-yr-old male bottlenose dolphin (Tursiops truncatus) developed an Aspergillus
      fumigatus pneumonia. Fungal elements were identified by cytology and microbiology
      from endoscopic bronchoalveolar lavage and brushings of a raised yellow
      endobronchial lesion. The results of qualitative immunodiffusion serology, a
      technique that identifies specific circulating antibodies to Aspergillus
      fumigatus, were suggestive of an active infection. The dolphin was treated with
      itraconazole for over 2 yr, which resulted in remission of clinical signs.
      Pneumonia caused by Aspergillus sp. accounts for the large majority of pulmonary
      mycoses in marine mammals. Bronchoscopy facilitated an early definitive
      diagnosis, accurate treatment, and remission.

PMID- 10065856
TI  - Disseminated histoplasmosis in an Atlantic bottlenose dolphin (Tursiops
      truncatus).
AB  - An approximately 37-yr-old female Atlantic bottlenose dolphin (Tursiops
      truncatus) died after a 4-mo illness characterized by intermittent anorexia,
      lethargy, mild neutrophilic leukocytosis, and mild nonregenerative anemia. At
      necropsy, the lungs were diffusely consolidated, and histopathology of the lungs
      revealed severe pneumonia with macrophages containing clusters of numerous yeast
      cells. Inflammatory lesions and yeast also were found in pulmonary, mediastinal,
      prescapular, and duodenal lymph nodes, spleen, liver, kidneys, urinary bladder,
      pancreas, right adrenal gland, and the pyloric stomach. Histomorphology, fungal
      culture, and polymerase chain reaction analysis indicated that the fungus was
      Histoplasma capsulatum var. capsulatum. This is the first report of
      histoplasmosis in a cetacean.

PMID- 10065857
TI  - Infectious dermatitis in a ball python (Python regius) colony.
AB  - Seven wild-caught ball pythons (Python regius), including six gravid females and
      one male, were obtained from Africa and were housed in a government animal
      facility in Research Triangle Park, North Carolina. Upon arrival, the snakes were
      found to be infested with ticks (Aponomma latus), which were manually removed.
      Four weeks following arrival, vesicular skin lesions began to appear on the
      snakes. Despite treatment of all affected female snakes with amikacin (5 mg/kg
      i.m., every 3 days) and cefotaxime (25 mg/kg i.m., every 3 days), the condition
      progressed and five of the female snakes died 7 wk after arrival. The remaining
      male and one female improved after an increase in environmental temperature, with
      ecdysis followed by healing. Physiologic stress, ectoparasites, and shipping may
      have predisposed the snakes to sepsis.

PMID- 10065858
TI  - Idiopathic distal esophageal dilation in a southern black rhinoceros (Diceros
      bicornis minor).
AB  - An adult female southern black rhinoceros (Diceros bicornis minor) experienced
      intermittent periods of regurgitation while eating, suggesting an esophageal
      disorder. Endoscopy for evaluation of the trachea, esophagus, and stomach
      revealed a 30-mm nasopharyngeal orifice with associated recess located in the
      caudodorsal pharynx and a 10-cm dilated segment of the distal esophagus that was
      presumably the cause of regurgitation. Dietary management of esophageal dilation
      through short-term utilization of a "soft feed" program successfully eliminated
      the regurgitation. This is the first report of esophageal dysfunction in a
      rhinoceros.

PMID- 10065859
TI  - Fibrocartilaginous emboli in a tayra (Eira barbara): a case report.
AB  - An 8-yr-old male tayra (Eira barbara) was presented with acute onset of pelvic
      limb paralysis. Radiography was unremarkable. Neurologic examination showed signs
      consistent with an intramedullary lesion between the second thoracic and fifth
      lumbar spinal cord segments. The animal's condition did not improve after 4 days
      of aggressive glucocorticoid therapy, and euthanasia was performed. Histologic
      examination of the spinal cord showed amorphous emboli suggestive of
      cartilaginous fragments within spinal veins. A diagnosis of fibrocartilaginous
      emboli was made, the first known case in a mustelid.

PMID- 10065860
TI  - Sporotrichosis in a nine-banded armadillo (Dasypus novemcinctus).
AB  - An adult female nine-banded armadillo (Dasypus novemcinctus) died in the
      quarantine station of a private Swiss zoo. Multifocal ulcerative skin lesions and
      multiple hemorrhages in the lungs were found at necropsy. The spleen was enlarged
      and dark red. Histologically, there was diffuse granulomatous infiltration,
      including multinucleated giant cells, of the skin lesions, lungs, spleen, liver,
      heart, and kidneys. Abundant periodic acid-Schiff-positive yeastlike cells were
      demonstrated intracellularly in giant cells and extracellularly scattered
      throughout the tissues. Morphology of the cells varied, with some nonbudding
      cells resembling Cryptococcus neoformans and others resembling Sporothrix
      schenckii. A diagnosis of sporotrichosis was confirmed by immunofluorescence
      studies. This is the first report of sporotrichosis in an armadillo in a
      zoological garden and the third report of sporotrichosis in D. novemcinctus.

PMID- 10065861
TI  - Systemic candidiasis in a cheetah (Acinonyx jubatus).
AB  - Systemic candidiasis, with involvement of the spleen, liver, kidneys, and lymph
      nodes, was diagnosed in a geriatric captive cheetah (Acinonyx jubatus). The
      animal had a long clinical history of intermittent chronic gastritis associated
      with Helicobacter acinonyx and chronic renal failure, both of which were
      repeatedly treated with broad-spectrum antimicrobial therapy. Following
      euthanasia, a postmortem examination showed numerous microabscesses and
      granulomas composed of degenerate eosinophils and containing asteroids or
      Splendore-Hoeppli material throughout the body. Yeast, pseudohyphae, and
      infrequently branching septate hyphae, demonstrated with special stains, were
      identified as a Candida sp. by fluorescent antibody testing. Low genetic
      variation in cheetahs may increase their susceptibility to infectious agents.
      Additional factors contributing to the overgrowth and dissemination of Candida
      sp. in this case may have included changes in the bacterial flora of the
      alimentary tract as a result of repeated antimicrobial therapy and alterations in
      the topography of the alimentary mucosa caused by chronic gastritis.

PMID- 10065862
TI  - Karyotyping of human oocytes by chromosomal analysis of the second polar bodies.
AB  - This paper describes a method for obtaining metaphase chromosomes from human
      second polar bodies. The second polar body nucleus was injected into the
      cytoplasm of an enucleated oocyte, which is activated shortly after injection.
      When the polar body nucleus is transformed into a haploid pronucleus, treatment
      with okadaic acid was used to induce premature chromosome condensation. A total
      of 25 analysable chromosome plates were obtained from 38 polar bodies karyotyped
      using this technique. Whole chromosome painting was used to detect second polar
      bodies (and respectively, oocytes) with unbalanced translocations. In combination
      with the first polar body analysis, this technique may be useful in
      preimplantation genetic diagnosis for patients carrying maternal translocations.

PMID- 10065863
TI  - The mechanism of action of epidermal growth factor and transforming growth factor
      alpha on aromatase activity in granulosa cells from polycystic ovaries.
AB  - We investigated aromatization and the mechanism of action of epidermal growth
      factor (EGF) and transforming growth factor alpha (TGFalpha) on oestradiol
      biosynthesis in freshly prepared granulosa cells from polycystic ovaries. Freshly
      prepared granulosa cells from polycystic ovaries incubated for only 3 h under
      basal conditions secreted significantly (P< 0.001) greater amounts of oestradiol
      17beta than that of granulosa cells from normal ovaries. 8-Bromo-cyclic adenosine
      monophosphate (8-Br-cAMP), but not follicle stimulating hormone (FSH) or
      luteinizing hormone (LH), further enhanced this activity. Both EGF and TGFalpha
      inhibited gonadotrophinor 8-Br-cAMP-stimulated, but not basal, oestradiol
      production. LH receptor (LHR) binding, estimated by immunolabelling the bound LH,
      was significantly (P< 0.001) reduced in granulosa cells from polycystic ovaries
      when compared with cells from normal ovaries. EGF or TGFalpha significantly
      reduced the binding in cultured cells from all patient groups (P< 0.05). More
      interestingly, a further increase of the inhibitory effect was seen in granulosa
      cells from polycystic ovaries (P < 0.001). In conclusion, granulosa cells from
      polycystic ovaries contain high levels of basal aromatase activity in vitro,
      which is probably inherited from the in-vivo condition. EGF and TGFalpha suppress
      oestradiol synthesis at a step beyond the production of cAMP and also LHR binding
      with more effect in granulosa cells from polycystic ovaries.

PMID- 10065864
TI  - Expression of relaxin-like factor is down-regulated in human testicular Leydig
      cell neoplasia.
AB  - In addition to their role in steroidogenesis in the male, testicular Leydig cells
      constitutively express large amounts of the peptide relaxin-like factor (RLF),
      also known as Ley-IL. The Leydig cell-derived RLF belongs to the insulin-like
      superfamily, which also includes relaxin, insulin and the insulin-like growth
      factors, and within the testis is a specific marker of Leydig cells. Little
      information is available either on the regulation of gene expression or on the
      function of this Leydig cell-derived peptide. In the present study we have
      investigated the expression pattern of human RLF in patients with rare Leydig
      cell hyperplasia and adenoma. The expression of both mRNA and protein appear to
      be decreased in hyperplastic Leydig cells, whereas in the Leydig cell adenomas
      studied, large central areas of the adenoma were devoid of RLF mRNA and protein.
      Only Leydig cells located at the periphery of the adenoma displayed expression of
      RLF, with full agreement between in-situ hybridization and immunohistochemistry.
      It thus appears that the expression of the RLF gene and its products are down
      regulated in Leydig cell hyperplasia and adenoma, consistent with a concomitant
      dedifferentiation of these cells.

PMID- 10065865
TI  - Binding of annexin V to plasma membranes of human spermatozoa: a rapid assay for
      detection of membrane changes after cryostorage.
AB  - When the cell membrane is disturbed, phospholipid phosphatidylserine (PS) is
      translocated from the inner to the outer leaflet of the plasma membrane. This is
      one of the earliest signs of apoptosis and can be monitored by the calcium
      dependent binding of annexin V. Therefore, annexin V-binding, in conjunction with
      flow cytometry, was used to evaluate the integrity of the sperm plasma membrane
      after different cryostorage protocols: i.e. 10% (v/v) glycerol; sperm maintenance
      medium (MM); freezing medium TEST yolk buffer (TYB); or cryostorage without
      protection (cryoshock). Using a combination of two fluorescent dyes, annexin V
      and propidium iodide (PI), led to three groups of spermatozoa being identified:
      (i) viable spermatozoa (annexin V-negative and PI-negative); (ii) dead
      spermatozoa (annexin V-positive and PI-positive); and (iii) cells with impaired
      but integer plasma membrane (annexin V-positive and PI-negative). The percentage
      of vital annexin V-negative spermatozoa increased significantly (P < 0.05) from
      spermatozoa treated by cryoshock (15.0+/-1.2%) to spermatozoa cryopreserved by
      TYB (26.6+/-2.2%) via cryopreservation by 10% (v/v) glycerol (19.9+/-1.6%) and by
      MM (22.2 1.8%) and was associated with the percentage of motile spermatozoa
      (17.6+/-3.4% by glycerol; 19.6+/-3.7% by MM and 22.6+/-3.9% by TYB; P = 0.0001).
      Of the spermatozoa, 12-22% were annexin V-positive even though they did not bind
      to PI, indicating viability before as well as after cryostorage. The percentage
      of vital annexin V-positive spermatozoa was significantly correlated with
      different sperm motility parameters (velocity straight linear, r = 0.601, P =
      0.018; percentage of linearly motile spermatozoa: r = 0.549, P = 0.034). We,
      therefore, concluded that annexin V-binding is more sensitive in detecting a
      deterioration of membrane functions than PI staining, and that a considerable
      percentage of spermatozoa might have dysfunctional plasma membranes besides dead
      or moribund cells. Of the cryopreservation protocols tested, TYB yielded the most
      viable spermatozoa. Therefore, we advocate the use of the annexin V-binding assay
      for the evaluation of the quality and integrity of spermatozoa.

PMID- 10065866
TI  - In-vitro fertilization and culture of mouse embryos in vitro significantly
      retards the onset of insulin-like growth factor-II expression from the zygotic
      genome.
AB  - In this study, the effect of in-vitro fertilization (IVF) and culture of mouse
      embryos in vitro on the normal expression of insulin-like growth factor-II (IFG
      II) ligand and receptor was examined. The expression of IGF-II increased in a
      linear fashion at least up to the 8-cell stage of development. IGF-II expression
      in embryos collected fresh from the reproductive tract was significantly (P <
      0.001) greater than in embryos fertilized in the reproductive tract and cultured
      in vitro (in-situ fertilized: ISF), and its expression was further reduced (P <
      0.001) in IVF embryos at all development stages tested. The expression of IGF-II
      was significantly (P < 0.001) lower when embryos were cultured individually in
      100 microl drops compared with culture in groups of 10 in 10 microl drops of
      medium. The addition of platelet activating factor to culture medium partially
      overcame this density-dependent decline of expression. Culture of ISF and IVF
      zygotes also caused the onset of new IGF-II mRNA transcription from the zygotic
      genome to be significantly (P < 0.001) retarded, until at least the 8-cell stage
      of development. This effect was greater (P < 0.05) for IVF than for ISF embryos.
      Neither IVF nor culture had any obvious effect on IFG-II/mannose-6-phosphate
      receptor (IGF-IIr) mRNA expression.

PMID- 10065867
TI  - Detection of benzo[a]pyrene diol epoxide-DNA adducts in embryos from smoking
      couples: evidence for transmission by spermatozoa.
AB  - Tobacco smoking is deleterious to reproduction. Benzo[a]pyrene (B[a]P) is a
      potent carcinogen in cigarette smoke. Its reactive metabolite induces DNA
      adducts, which can cause mutations. We investigated whether B[a]P diol epoxide
      (BPDE) DNA adducts are detectable in preimplantation embryos in relation to
      parental smoking. A total of 17 couples were classified by their smoking habits:
      (i) both partners smoke; (ii) wife non-smoker, husband smokes; and (iii) both
      partners were non-smokers. Their 27 embryos were exposed to an anti-BPDE
      monoclonal antibody that recognizes BPDE-DNA adducts. Immunostaining was assessed
      in each embryo and an intensity score was calculated for embryos in each smoking
      group. The proportion of blastomeres which stained was higher for embryos of
      smokers than for non-smokers (0.723 versus 0.310). The mean intensity score was
      also higher for embryos of smokers (1.40+/-0.28) than for non-smokers (0.38+/
      0.14; P = 0.015), but was similar for both types of smoking couples. The mean
      intensity score was positively correlated with the number of cigarettes smoked by
      fathers (P = 0.02). Increased mean immunostaining in embryos from smokers,
      relative to non-smokers, indicates a relationship with parental smoking. The
      similar levels of immunostaining in embryos from both types of smoking couples
      suggest that transmission of modified DNA is mainly through spermatozoa. We
      confirmed paternal transmission of modified DNA by detection of DNA adducts in
      spermatozoa of a smoker father and his embryo.

PMID- 10065868
TI  - Fertilization, embryonic development, and offspring from mouse eggs injected with
      round spermatids combined with Ca2+ oscillation-inducing sperm factor.
AB  - Round spermatids, precursor male gametes, are known to possess the potential to
      achieve fertilization and embryonic development when injected into eggs. However,
      injection of spermatids alone seldom activates eggs in the mouse, as spermatids
      by themselves cannot induce an increase in intracellular Ca2+, a prerequisite for
      egg activation. We injected a mouse round spermatid into an egg simultaneously
      with partially purified sperm factor from differentiated hamster spermatozoa. The
      combined injection produced repetitive Ca2+ increases (Ca2+ oscillations) lasting
      for at least 4 h as observed at fertilization, and induced activation in 92% of
      eggs. This method provided 75% fertilization success associated with male and
      female pronucleus formation and development to 2-cell embryos, while only 7% of
      eggs were fertilized by injection of a spermatid alone. Of the 2-cell embryos,
      approximately 50% developed to blastocysts during 5 days of culture in vitro,
      while no blastocysts were obtained following injection of sperm factor alone.
      Furthermore, the 2-cell embryos, that were created by spermatids and sperm factor
      and transplanted into foster mothers, developed into normal offspring, although
      the percentage was only 22%. All infants grew into healthy adults carrying normal
      chromosomes. The sperm factor served as a complementary factor for successful
      fertilization by round spermatid injection.

PMID- 10065870
TI  - Tumour necrosis factor-alpha (TNF-alpha) in human endometrium and uterine
      secretion: an evaluation by immunohistochemistry, ELISA and semiquantitative RT
      PCR.
AB  - Tumour necrosis factor-alpha (TNF-alpha is a pleiotropic cytokine synthesized
      throughout the female reproductive tract. Even though evidence has accumulated
      that supports its role in autocrine and paracrine processes, its expression and
      function in the human endometrium are still not completely understood. To gain a
      better understanding of the synthesis and release of TNF-alpha in the endometrium
      and how this relates to concentrations in uterine secretion, its expression
      throughout the menstrual cycle was investigated by three different techniques.
      Samples of endometrial tissue and uterine secretions were collected from patients
      undergoing abdominal and vaginal hysterectomy for benign reasons. The mRNA
      expression of TNF-alpha was investigated in homogenized endometrial tissue by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) (n =
      18). An assessment of the cellular TNF-alpha protein localization in the
      endometrial glands was performed immunohistochemically (n = 39). The
      concentrations of the secreted TNF-alpha protein in endometrial secretion were
      determined by enzyme-linked immunosorbent analysis (n = 30). All three methods
      gave similar results on the temporal expression of TNF-alpha mRNA and TNF-alpha
      protein during the cycle. Concentrations of endometrial TNF-alpha mRNA in tissue
      samples and TNF-alpha protein in uterine secretion were quite low at the
      beginning of the cycle, rose sharply in the mid- to late proliferative phase and
      decreased towards the end of the cycle. The concentrations of TNF-alpha protein
      in the endometrial glands, as shown by immunohistochemical investigation, stayed
      high throughout the secretory phase at values slightly below those of the late
      proliferative phase.

PMID- 10065869
TI  - Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells
      through the induction of alpha-smooth muscle actin, calponin h1 and p27.
AB  - Mast cells are widely distributed in human tissues, including the human uterus.
      However, the function of mast cells in uterine smooth muscle has not been clearly
      established. Mast cells possess secretory granules containing such substances as
      heparin, serotonin, histamine and many cytokines. To help establish the role of
      mast cells in the human myometrium, the action of heparin was investigated using
      smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The
      proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin
      treatment. Flow cytometric analysis showed that the population in the G1 phase of
      the cell cycle increased under heparin treatment. Western blotting analysis
      showed that markers of SMC differentiation such as alpha-smooth muscle actin
      (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced
      by heparin, whereas cell-cycle-related gene products from the G1 phase of the
      cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these
      results indicate that heparin inhibits the proliferation of myometrial and
      leiomyomal SMC through the induction of alpha-SMA, calponin h1 and p27. We
      suggest that heparin from mast cells may induce differentiation in uterine SMC
      and may influence tissue remodelling and reconstruction during physiological and
      pathophysiological events.

PMID- 10065871
TI  - Expression of calcium binding protein D-9k messenger RNA in the mouse uterine
      endometrium during implantation.
AB  - To investigate the molecular mechanisms of implantation, we constructed a cDNA
      library of mouse uteri enriched with pregnancy-induced genes by subtractive
      hybridization and polymerase chain reaction (PCR). One of the isolated clones was
      the cDNA for the calcium binding protein D-9k (Cabp9k), which is considered to
      regulate intracytoplasmic concentration and transport of free calcium ions.
      Northern blot and in-situ hybridization analyses demonstrated that the Cabp9k
      mRNA was expressed in the endometrial epithelia, both luminal and glandular, in
      the uterus at the time of implantation. On pregnancy day 5 it was detected in the
      luminal, but not in the glandular, epithelia. In the oophorectomized adult mice,
      progesterone enhanced Cabp9k mRNA expression in the uterus, whereas oestrogen did
      not. Consistent with this, a nucleotide change was identified in the first intron
      of mouse Cabp9k gene corresponding to the oestrogen responsive element in the rat
      Cabp9k gene. Transfer of embryos into the uterine cavity of pseudopregnant mice
      reduced the expression of Cabp9k mRNA in the glandular epithelium, suggesting
      that Cabp9k mRNA expression is also regulated by embryonal signal(s). These
      findings demonstrated that Cabp9k mRNA is expressed in the endometrial epithelia
      during the implantation period under the control of progesterone and the presence
      of embryo, and suggest that CaBP9k plays a role in implantation by regulating the
      local calcium concentrations.

PMID- 10065872
TI  - CD9 is expressed in extravillous trophoblasts in association with integrin alpha3
      and integrin alpha5.
AB  - The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related
      to Schwann cell migration and adhesion. In this study, we examined the expression
      of CD9 in human extravillous trophoblasts, which invade into the endometrium
      during implantation and placentation. CD9 was detected immunohistochemically on
      the extravillous trophoblasts in the cell columns of first trimester placentae,
      but not on villous trophoblasts. In the second and third trimester, CD9 was
      highly expressed on the extravillous trophoblasts in the basal plate of
      placentae, and in the chorion laeve in the fetal membrane of term placentae. The
      molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western
      blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse
      transcription-polymerase chain reaction (RT-PCR). Proteins were purified from
      chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5
      monoclonal antibodies and Western blotting, revealed that CD9 was associated with
      both integrins. These findings indicate that CD9 is a differentiation-related
      molecule present in the extravillous trophoblasts. Since it is associated with
      integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may
      be implicated in trophoblast invasion at the feto-maternal interface.

PMID- 10065873
TI  - CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line,
      BeWo cells.
AB  - The CD9 molecule is expressed on human extravillous trophoblasts, which invade
      the endometrium during implantation and placentation. To elucidate the role of
      CD9 in trophoblastic function, we investigated the expression of CD9 protein and
      mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using
      immunohistochemistry, Western blotting and reverse transcription-polymerase chain
      reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal
      antibodies (mAb), their invasion through the extracellular matrices was
      significantly enhanced in a dose-dependent manner. Cell proliferation and human
      chorionic gonadotrophin production were unaffected. On the other hand, culture in
      the presence of mAb against integrins alpha3, alpha5 and beta1, which partially
      block the interaction with the extracellular matrices, inhibited BeWo cell
      invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell
      invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no
      effect in the presence of mAb against integrins alpha5 and beta1, which were also
      highly expressed on BeWo cells. These findings suggest that CD9 has a function
      connected with the invasive properties of BeWo cells, which is partially mediated
      by integrin alpha5beta1. This may relate to the involvement of CD9 in
      trophoblastic invasion.

PMID- 10065874
TI  - Myometrial constitutive nitric oxide synthase expression is increased during
      human pregnancy.
AB  - Nitric oxide (NO), derived from L-arginine by the action of nitric oxide synthase
      (NOS), is a mediator of many diverse biological activities, including
      vasodilation, neurotransmission and inhibition of platelet adhesion. A role for
      NO in the maintenance of rat and rabbit pregnancy is supported by a variety of
      studies. A recent study in women demonstrated that myometrial inducible NOS
      (iNOS) expression was greater in the early third trimester than either the late
      third trimester or in the non-pregnant condition, suggesting that increased iNOS
      expression is involved in the maintenance of human pregnancy. Constitutive NOS
      (cNOS) expression was not determined. The aim of this study was to compare
      constitutive NOS (both eNOS and bNOS) expression in the human non-pregnant
      uterus, preterm pregnant uterus (25-34 weeks gestation) and term pregnant uterus
      (>37 weeks gestation) using immunohistochemistry and Western blotting. Preterm
      pregnant samples were taken from women with a variety of pathologies
      necessitating early delivery. We found that eNOS and bNOS protein concentrations
      were greater in the preterm pregnant myometrium than non-pregnant myometrium.
      eNOS, but not bNOS, protein concentration was lower in myometrial samples
      obtained at term compared with those obtained preterm. We conclude that the
      constitutive isoforms of NOS are also up-regulated in human pregnancy and may
      play a role in the maintenance of myometrial quiescence.

PMID- 10065875
TI  - Prostaglandin endoperoxide H synthase mRNA expression in the human amnion and
      decidua during pregnancy and in the amnion at preterm labour.
AB  - We have examined the expression of prostaglandin endoperoxide H synthase (PGHS)
      isoenzymes in the amnion and the decidua during gestation, and the abundance of
      PGHS mRNA in the amnion at idiopathic preterm labour. PGHS-1 and -2 mRNA
      abundance in the amnion, determined with ribonuclease protection assays, was
      significantly (P< 0.05) higher at term than earlier during pregnancy. In
      contrast, neither PGHS-1 and -2 mRNA values, nor PGHS-specific activity, measured
      with a cell-free assay, was different in the decidua at term as compared to
      earlier gestational ages. In individual term patients, PGHS-2 mRNA values in the
      amnion were positively correlated with PGHS-2 mRNA values in the chorion laeve.
      PGHS-1 and -2 mRNA abundance was higher (P < 0.05) in the amnion after idiopathic
      preterm labour than in the absence of labour at the same gestational age (28-35
      weeks). Thus, PGHS-1 and -2 are induced in the amnion at term. Furthermore,
      amniotic PGHS-2 changes in co-ordination with PGHS-2 concentrations in the
      chorion laeve. PGHS is not induced in the decidua at term. Increased amniotic
      PGHS expression may contribute to the enhanced intrauterine prostaglandin
      synthesis before term labour. Both PGHS isoenzymes may participate in the
      increase of PGHS activity in the amnion at preterm birth.

PMID- 10065876
TI  - Ovarian steroids and serotonin neural function.
AB  - The serotonin neural system originates from ten nuclei in the mid- and hindbrain
      regions. The cells of the rostral nuclei project to almost every area of the
      forebrain, including the hypothalamus, limbic regions, basal ganglia, thalamic
      nuclei, and cortex. The caudal nuclei project to the spinal cord and interact
      with numerous autonomic and sensory systems. This article reviews much of the
      available literature from basic research and relevant clinical research that
      indicates that ovarian steroid hormones, estrogens and progestins, affect the
      function of the serotonin neural system. Experimental results in nonhuman
      primates from this laboratory are contrasted with studies in rodents and humans.
      The sites of action of ovarian hormones on the serotonin neural system include
      effects within serotonin neurons as well as effects on serotonin afferent neurons
      and serotonin target neurons. Therefore, information on estrogen and progestin
      receptor-containing neurons was synthesized with information on serotonin
      afferent and efferent circuits. The ability of estrogens and progestins to alter
      the function of the serotonin neural system at various levels provides a cellular
      mechanism whereby ovarian hormones can impact mood, cognition, pain, and numerous
      other autonomic functions.

PMID- 10065878
TI  - Glucagon-like peptide-1 (7-36) amide as a novel neuropeptide.
AB  - Although earlier studies indicated that GLP-1 (7-36) amide was an intestinal
      peptide with a potent effect on glucose-dependent insulin secretion, later on it
      was found that several biological effects of this peptide occur in the brain,
      rather than in peripheral tissues. Thus, proglucagon is expressed in pancreas,
      intestine, and brain, but post translational processing of the precursor yields
      different products in these organs, glucagon-like peptide-1 (7-36) amide being
      one of the forms produced in the brain. Also, GLP-1 receptor cDNA from human and
      rat brains has been cloned and sequenced, and the deduced amino acid sequences
      are the same as those found in pancreatic islets. Through these receptors, GLP-1
      (7-36) amide from gut or brain sources induces its effects on the release of
      neurotransmitters from selective brain nuclei, the inhibition of gastric
      secretion and motility, the regulation of food and drink intake,
      thermoregulation, and arterial blood pressure. Central administration (icv) of
      GLP-1 (7-36) amide produces a marked reduction in food and water intake, and the
      colocalization of the GLP-1 receptor, GLUT-2, and glucokinase mRNAs in
      hypothalamic neurons involved in glucose sensing suggests that these cells may be
      involved in the transduction of signals needed to produce a state of fullness. In
      addition, GLP-1 (7-36) amide inhibits gastric acid secretion and gastric
      emptying, but these effects are not found in vagotomized subjects, suggesting a
      centrally mediated effect. Similar results have been found with the action of
      this peptide on arterial blood pressure and heart rate in rats. Synthesis of GLP
      1 (7-36) amide and its own receptors in the brain together with its
      abovementioned central physiological effects imply that this peptide may be
      considered a neuropeptide. Also, the presence of GLP-1 (7-36) amide in the
      synaptosome fraction and its calcium-dependent release by potassium stimulation,
      suggest that the peptide may act as a neurotransmitter although further
      electrophysiological and ultrastructural studies are needed to confirm this
      possibility.

PMID- 10065879
TI  - History and fundamentals of gait analysis.

PMID- 10065877
TI  - The regulation of neurotransmitter secretion by protein kinase C.
AB  - The effect of protein kinase C (PKC) on the release of neurotransmitters from a
      number preparations, including sympathetic nerve endings, brain slices,
      synaptosomes, and neuronally derived cell lines, is considered. A comparison is
      drawn between effects of activation of PKC on neurotransmitter release from small
      synaptic vesicles and large dense-cored vesicles. The enhancement of
      neurotransmitter release is discussed in relation to the effect of PKC on: 1.
      Rearrangement of the F-actin-based cytoskeleton, including the possible role of
      MARCKS in this process, to allow access of large dense-cored vesicles to release
      sites on the plasma membrane. 2. Phosphorylation of key components in the
      SNAP/SNARE complex associated with the docking and fusion of vesicles at site of
      secretion. 3. Ion channel activity, particularly Ca2+ channels.

PMID- 10065880
TI  - Practical and theoretical considerations in the application in the development of
      clinical gait analysis.

PMID- 10065881
TI  - Body up-down acceleration in kinematic gait analysis in comparison with the
      vertical ground reaction force.
AB  - In order to investigate clinical significance of the body up-down acceleration,
      and to practically verify the relationship with the vertical component of the
      ground reaction force, 3D kinematic gait analysis was performed on normal
      subjects and hip patients. The displacement of the body up-down movement was
      measured at the lower end of the sternum, then the acceleration was calculated
      from the displacement by using the double differential operation, and
      differential noise was removed by Finite Impulse Response (FIR) digital filter
      with the cutoff frequency of 3 Hz. The acceleration showed a regular cyclic
      pattern in normal subjects. However, in hip patients, there was a significant
      decrease of downward acceleration at the mid-stance of the affected side. And the
      acceleration was roughly consistent with the vertical component showing the same
      trends of up and down. However, in detail, they are inconsistent in the affected
      side, which is probably due to abnormal movements of the body and upper limbs,
      the so-called compensational movements.

PMID- 10065882
TI  - Influences of walking speed change on the lumbosacral joint force distribution.
AB  - To more understand the influence of the walking speed on the spinal joint force
      distribution, a three-dimensional biomechanical model was used to estimate the
      spine loads during human gait with three different walking speeds. This
      previously developed and validated model included a dynamic external model and an
      internal model with forces of disc, 8 major muscles, 2 ligaments and 2 facet
      joints at L5/S1 level. A linear optimization method was used to solve the
      internal model to estimate the L5/S1 spinal joint force distribution. The results
      of five young male subjects showed that the mean peak L5/S1 disc compressive
      forces on the slow, preferred and fast speeds were 2.28, 2.53, 2.95 body weight,
      respectively. The peak forces happened right after the heel strike and before
      completely toe off. The facet joint forces were generally increased with the
      walking speed increase, too. To reduce the loads on the spine, the slow walking
      is then recommended for the patients with low back pain or after spinal surgery.

PMID- 10065883
TI  - Clinical study on arthroplasties for osteoarthritic hip by quantitative gait
      analysis. Comparison between total hip arthroplasty and bipolar endoprosthetic
      arthroplasty.
AB  - The present study was undertaken to serially observe gait of patients after hip
      arthroplasty, using quantitative gait analysis, and to compare it between
      patients after total hip arthroplasty (THA) and those after bipolar
      endoprosthetic arthroplasty (BEA). The subjects were 53 women with unilateral
      osteoarthritis of the hip. Thirty-one of them underwent THA (mean age: 59.5
      years) and 22 underwent BEA (mean age: 58.0 years). The stance time and
      characteristic parameters calculated from the vertical component of floor
      reaction force (FRF) were analyzed by use of FRF plate. The stance time, which
      indirectly represents the walking speed, tended to decrease for one year after
      THA and for 3 years after BEA. The decrease in this parameter was greater on the
      unaffected side than on the affected side. The deceleration effect and the
      weighing-off effect are indicators useful for observation of gait recovery.
      Significant differences in these indicators between the unaffected and affected
      sides were seen for one year after THA and 3 years after BEA. This indicates that
      cadence and balance of the gait recovers earlier after THA than after BEA.

PMID- 10065884
TI  - Gait analysis before or after varus osteotomy of the femur for hip
      osteoarthritis.
AB  - SUMMARY OF BACKGROUND: Intertrochanteric varus osteotomy of the femur for hip
      osteoarthritis is expected to bring improved congruity and increased weight
      bearing surface area of the hip joint. Before surgery, we usually make a tracing
      on a paper using an anteroposterior roentgenogram of the hip to simulate the
      operating procedures and obtain better conditions in the hip. Nevertheless, there
      have been some cases in which this procedure does not provide satisfactory
      postoperative results in terms of relief of pain or locomotion, with long-term
      limp due to weakness of the hip abductor muscle group and shortening of the leg.
      OBJECTIVES: To confirm if the improved congruity and increased covering of the
      weight-bearing surface area obtained by varus osteotomy can be actually
      reproduced during walking, and to evaluate the kinetic mechanism of the effects
      of this procedure using gait analysis. METHODS: We measured the strength ratio of
      the hip abductor muscles as the percent of the opposite side, and analyzed the
      pelvic movement and data of dynamic electromyography (EMG) recorded during
      locomotion in 24 female patients who underwent unilateral intertrochanteric varus
      osteotomy of the femur for hip osteoarthritis, 30 non-surgically-treated female
      patients with hip osteoarthritis, and 54 healthy women. In the operated patients,
      the roentgenograms obtained during one-legged stance on the affected side
      disclosed that 10 were positive for Trendelenburg's phenomenon (T(+) group) and
      14 were negative for Trendelenburg's phenomenon (T(-) group). All subjects walked
      with bare feet at a comfortable pace on a walkway containing a force plate. Photo
      switches were placed in a walkway to measure the gait velocity and to determine
      the stance phase time of one gait cycle. Frontal and sagittal trajectories of
      body surface markers for computerized joint-angle motion analysis were acquired
      using the Quick-MAG system. EMG data for the gluteus maximus, gluteus medius,
      tensor fascia latae, and lateral hamstrings recorded using surface electrodes
      were integrated to quantify as the percent of maximum voluntary contraction (%
      MVC). RESULTS: This study disclosed that the stance phase time was shorter and
      the strength ratio of the hip abductor muscles was lower in the operated patients
      than those in the other 2 groups, and the change of the pelvic obliquity was
      smaller and the % MVC of the gluteus medius and tensor fascia latae were greater
      than those in the normal subjects. The change of the pelvic tilt showed the same
      pattern with those of the pelvic obliquity. The T(+) group showed decreased
      strength ratio of the hip abductor muscles and increased % MVC for the gluteus
      medius and the tensor fascia latae compared to the T(-) group, but the changes of
      both the pelvic obliquity and pelvic tilt did not significantly differ in the 2
      groups. CONCLUSION: This study showed the postoperative reappearance of the
      simulated conditions in the hip before varus osteotomy of the femur, providing
      evidence that the pelvis was horizontally maintained during walking due to
      decreased stance phase time and increased performance of the hip abductor muscles
      after this procedure.

PMID- 10065885
TI  - Gait analysis of patients with osteoarthritis of the hip and the those with total
      hip arthroplasty.

PMID- 10065886
TI  - Three-dimensional knee motion analysis for the pathogenesis knee osteoarthrosis.
AB  - To discuss the pathogenesis of knee OA, the relationships of the risk factors
      which are detected by the epidemiological study are explained by the three
      dimensional motion analysis.

PMID- 10065887
TI  - Measurements of joint moment and knee flexion angle of patients with anterior
      cruciate ligament deficiency during level walking and on one leg hop.

PMID- 10065888
TI  - Gait analysis of ACL deficient knees. Angular velocities and flexion-extension
      moment around the knee joint.

PMID- 10065889
TI  - Graphics-based modeling and analysis of gait abnormalities.

PMID- 10065890
TI  - Control of FES in paraplegia: modeling voluntary arm forces.
AB  - Skilled behavior is difficult or impossible to articulate explicitly by the
      performers. Likewise biomechanical models of skilled motor actions are often
      limited by the lack of knowledge of the underlying mechanisms. A 'behavioral
      cloning' technique is described, based on a trained artificial neural network
      (ANN), that precisely mimics an individual's learned skill. In this paper the
      motor skill considered is that of paraplegics using their upper limbs whilst
      standing-up with FES. In a group of eight paraplegics with complete spinal
      injuries, it was possible to develop clones that followed closely the observed
      behavior of the subjects. Each subject used a unique and consistent voluntary
      control strategy. Subjects with more experience in using FES were more consistent
      in the use of their arms from trial to trial. Comparison of the clones revealed
      features suggestive of some common underlying voluntary control strategies.

PMID- 10065891
TI  - The combination of magnetic resonance angiography and computational fluid
      dynamics: a critical review.
AB  - Computational Fluid Dynamics (CFD) has proven to be a valuable technique in the
      study of blood flow in arteries because of its capability of obtaining
      quantitatively velocities and wall shear stress. However, the "bottleneck"
      problem limiting the application of CFD is the difficulty of constructing
      anatomically realistic arterial geometries. In this survey, an overview is
      presented of the progress over the last decade in the development of magnetic
      resonance angiography (MRA) techniques, medical image processing and CFD, as well
      as the combination of these techniques in hemodynamics research. It is
      demonstrated that with modern angiographic techniques such as MRA, noninvasive
      measurement of human angiograms becomes possible and practical. Together with
      digital medical image processing and analysis techniques, computational models
      can be constructed for the "real" human arteries without making any geometric
      assumptions. When allied with state-of-the-art CFD codes, velocity and wall shear
      stress distributions, as well as particle trajectories, can be determined in the
      arteries.

PMID- 10065892
TI  - A review of nondestructive test methods and their application to measure the
      stability and osseointegration of bone anchored endosseous implants.
AB  - Threaded and cylindrical metallic endosseous implants are being used increasingly
      in cranio-facial, dental, and orthopedic surgery. There is a significant need for
      the development of quantitative noninvasive test methods to measure implant
      stability and success. Such success can be quantified by measurements of the
      stiffness and damping of an implant in the surrounding bone, and also the height
      of the marginal bone around an implant. In the case of a failing implant, the
      bone around it is replaced by fibrous tissue, and in the case of an overloaded
      implant the bone height around the implant falls. Nondestructive test methods
      have been applied to the testing of implant and tooth mobility, and commonly
      these have used transient or steady-state test methods. Transient methods entail
      tapping an implant, measuring its response and then performing a Fast Fourier
      Transform to resolve the fundamental frequencies. Steady-state methods measure
      the frequency response of a system using a swept frequency wave form. A number of
      dedicated electronic instruments have been designed to perform these tasks, and
      this article discusses their applications, accuracy, and value as clinical
      diagnostic instruments.

PMID- 10065893
TI  - The G20210A mutation of the prothrombin gene in patients with previous first
      episodes of deep-vein thrombosis: prevalence and association with factor V
      G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels.
AB  - A common G to A transition at nucleotide 20210 of the prothrombin gene is
      associated with an increased risk for deep-vein thrombosis (DVT) and high plasma
      levels of prothrombin. We calculated the prevalences of prothrombin G20210A,
      factor V G1691A (also associated with high risk for DVT) and homozygous
      methylenetetrahydrofolate reductase (MTHFR) C677T (associated with increased
      susceptibility to develop hyperhomocysteinemia) in 118 patients with a first
      episode of DVT and in 416 healthy controls. 15.9% of the patients and 2.3% of the
      controls had prothrombin G20210A (odds ratio [OR]: 8.7, 95% C.I.: 3.8-21.4);
      21.1% of the patients and 3.2% of the controls had factor V G1691A (OR 7.8, 3.9
      17.1); 20.5% of the patients and 21% of the controls had homozygous MTHFR C677T
      (OR: 1.0, 0.7-1.2). Exclusion of patients with other hereditary risk factors for
      DVT did not substantially modify the results. Mutant factor V and prothrombin
      coexisted in three patients but in no control. The concomitant presence of the
      MTHFR mutation did not increase the thrombotic risk associated with prothrombin
      G20210A. 63.2% of individuals with prothrombin G20210A had plasma levels of
      prothrombin in the upper quartile of distribution. After adjustment for age and
      sex, subjects with prothrombin levels in the upper quartile carried a slightly
      higher risk for thrombosis than those with lower prothrombin concentrations (OR:
      1.9, 1.1-3.2). In conclusion, we found that prothrombin G20210A is relatively
      common in Italy and is associated with high prothrombin levels and an 8.7-fold
      increase in the risk for DVT. Such risk is independent of the coexistence of
      other known inherited risk factors for thrombosis and increases in patients with
      associated mutant factor V. Whether it is due to the associated increase in
      plasma prothrombin levels remains to be established.

PMID- 10065894
TI  - Antithrombotic effects of (n-3) polyunsaturated fatty acids in rat models of
      arterial and venous thrombosis.
AB  - The antithrombotic effects of dietary lipids were investigated in rat models of
      arterial and venous thrombosis. In the arterial model, thrombus formation was
      evaluated by determination of the occlusion time and the deposition of 111In
      labeled platelets and 125I-labeled fibrinogen in a collagen-coated glass
      capillary inserted into an arterio-arterial shunt. Venous thrombosis was
      evaluated by measurement of the thrombus weight after administration of
      thromboplastin as a source of tissue factor and establishment of stasis in the
      vena cava. Diets were supplemented with saturated (SAT group) or (n-3) fatty
      acids, the latter being added either as MaxEPA oil (MaxEPA group), or as
      docosahexaenoic (DHA group) or eicosapentaenoic (EPA group) ethyl ester. Only the
      MaxEPA group displayed a prolonged occlusion time as compared with all other
      groups. Platelet accumulation, similar in the MaxEPA, EPA and DHA groups (13.3,
      16.7 and 17.7 x 10(6) platelets/shunt, respectively), was significantly higher in
      the SAT group (25.3 x 10(6) platelets/shunt), while accumulation of fibrinogen
      fibrin was similar whatever the group. There was a trend towards a lower venous
      thrombus weight in MaxEPA fed rats relative to those fed other diets. Our data
      indicate that the MaxEPA diet had antithrombotic effects in arterial and to a
      lesser extent venous thrombosis models, best attributed to its multiple targeting
      of platelets and coagulation.

PMID- 10065895
TI  - Plasma tissue factor pathway inhibitor and tissue factor antigen levels after
      administration of heparin in patients with angina pectoris.
AB  - The hypercoagulability is associated with expression of tissue factor in patients
      with angina. Tissue factor pathway inhibitor regulates the extrinsic coagulation
      pathway mediated by tissue factor. Plasma samples were obtained from 14 patients
      with angina pectoris and 9 with chest pain syndrome before and 5, 30, 60, and 120
      minutes after administration of heparin (50 IU/kg). The tissue factor and
      prothrombin fragment 1+2 levels before administration were elevated in patients
      with angina pectoris and were reduced to the levels of chest pain syndrome after
      the administration. The free tissue factor pathway inhibitor levels after the
      administration were higher in patients with angina pectoris than in patients with
      chest pain syndrome. Plasma tissue factor pathway inhibitor levels correlated
      positively with plasma tissue factor and prothrombin fragment 1+2 levels. We
      showed that plasma-free TFPI levels after administration of heparin, which may
      indicate endothelial cell associated TFPI levels, increased in patients with
      angina pectoris compared with patients with chest pain syndrome. Increased
      endothelial cell associated TFPI was associated with hypercoagulability in
      patients with angina pectoris. These may help to explain the reduction in
      thrombotic risk associated with the use of heparin.

PMID- 10065896
TI  - On the control of the plasma contact activation system on human endothelium:
      comparisons with heparin surface.
AB  - The endothelial lining in segments of the human saphenous vein harvested before
      and shortly after systemic heparinization of patients was investigated with
      regard to the ability to inhibit activated FXII. Comparisons were made with a
      surface modified by endpoint attached heparin, which, like the endothelium, is
      negatively charged and exposes the specific antithrombin binding sequence and
      also binds FXII and antithrombin. The heparin surface preincubated with plasma or
      blood and endothelium in vivo having been exposed to non-heparinzed blood and
      expressed similar amounts of FXII but no FXIIa. On both surfaces activation of
      bound FXII with ellagic acid resulted in consumption of the proenzyme and in
      inhibition of formed FXIIa. On both heparin surface and the endothelium
      consumption of antithrombin occurred concomitantly, demonstrating the importance
      of this inhibitor in the control of contact activation system. On the
      endothelium, in vivo or ex vivo, exposed to heparinized blood, most FXII was
      present in the active form and only incubation with purified antithrombin could
      restore the FXIIa inhibitory capacity. It is suggested that antithrombin bound by
      the specific antithrombin binding sequence of endothelial heparan sulphate, like
      antithrombin bound to the specific antithrombin binding sequence on heparin
      surface, inhibits alpha-FXIIa. This makes the endothelium consonant with the
      plasma contact activation system. It is suggested that systemic heparinzation of
      patients may both activate endothelial bound FXII and interfere in the inhibition
      of formed FXIIa by depriving the endothelium of required amounts of antithrombin.

PMID- 10065897
TI  - Variables affecting the transduction efficiency of adenovirus vectors in bovine
      aortic endothelial cells.
AB  - Features and kinetics of Adenovirus (Ad)-mediated gene transfer to endothelial
      cells (EC) are not ultimately determined. We tested variables pertinent to the
      efficiency of Ad-mediated gene transfer to bovine aortic endothelial cells (BAEC)
      including: (1) Ad-vectors with different promoters, (2) kinetics of transduction
      efficiency of LacZ gene to BAEC, (3) the concentration and volume of vector
      containing medium, (4) the period of incubation time of Ad vectors with BAEC, (5)
      the duration of transgene expression. An Ad5-LacZ vector with a cytomegalovirus
      (CMV) promoter transduced the LacZ gene to the cells more efficiently than
      vectors with the Rous sarcoma virus (RSV) promoter. However, both vectors
      exhibited a dose-dependent relationship between the vector multiplicity of
      infection (moi) and the percentage of LacZ-expressing cells. The higher moi of
      both vectors achieved nearly 100% of transduction efficiency in cultured BAEC.
      Although the Ad-CMV-LacZ vector better transduced the LacZ gene to BAEC than Ad
      RSV-LacZ, a long period of vector exposure to BAEC could overcome the slightly
      difference in transduction efficiency between the two vectors. These results
      indicate that both Ad vectors are efficient for gene transfer to endothelial
      cells, and higher moi of vectors or a longer period exposure of vectors to EC can
      facilitate efficient transduction of foreign gene into EC in culture.

PMID- 10065898
TI  - In vivo antithrombotic effects of a nitric oxide-releasing aspirin derivative,
      NCX-4016.

PMID- 10065899
TI  - The CXC-chemokine, H174: expression in the central nervous system.
AB  - H174 is a new member of the CXC-chemokine family. A cDNA probe containing the
      entire H174 coding region recognized a predominant inducible transcript of
      approximately 1.5 kb expressed in interferon (IFN) activated astrocytoma and
      monocytic cell lines. H174 message can be induced following IFN-alpha, IFN-beta,
      or IFN-gamma stimulation. H174 message was also detected in IFN treated cultures
      of primary human astrocytes, but was absent in unstimulated astrocytes. H174,
      like IP10 and Mig, lacks the ELR sequence associated with the neutrophil
      specificity characteristic of most CXC-chemokines. Preliminary experiments
      suggest H174, IP10 and Mig are independently regulated. Recombinant H174 is a
      weak chemoattractant for monocyte-like cells. H174 can also stimulate calcium
      flux responses. The data support the classification of H174 as a member of a
      subfamily of interferon-gamma inducible non-ELR CXC-chemokines. Brain tissues
      were obtained at autopsy from one patient with AIDS dementia, one patient with
      multiple sclerosis, and two normal control patients. H174 and Mig were detected
      by RT-PCR in brain tissue cDNA derived from the patients with pathological
      conditions associated with activated astrocytes but not in cDNA from control
      specimens.

PMID- 10065900
TI  - Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic
      HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.
AB  - In order to examine the effect of HTLV-I proviral load on the pathogenesis of
      HAM/TSP, we measured the HTLV-I proviral load in peripheral blood mononuclear
      cells (PBMC) from a large number of HAM/TSP patients and asymptomatic HTLV-I
      carriers. To measure the proviral load, we used an accurate and reproducible
      quantitative PCR method using a dual-labeled fluorogenic probe (ABI PRISM 7700
      Sequence Detection System). The mean +/- standard error of mean (s.e.m.) HTLV-I
      proviral copy number per 1 x 10(4) PBMC was 798 +/- 51 (median 544) in 202
      HAM/TSP patients; 120 +/- 17 (median 34) in 200 non HAM-related (general)
      asymptomatic HTLV-I carriers (RC); and 496 +/- 82 (median 321) in 43 asymptomatic
      HTLV-I carriers genetically related to HAM/TSP patients (FA). The prevalence of
      HAM/TSP rises exponentially with log (proviral load) once the proviral load
      exceeds 1% PBMC. The HTLV-I proviral load of female patients with HAM/TSP was
      significantly higher than that of male patients, however there was no significant
      difference in proviral load between sexes in RC. There was a significant
      correlation between the proviral load and the concentration of neopterin in CSF
      of HAM/TSP patients. These results indicate that the HTLV-I proviral load in PBMC
      may be related to the inflammatory process in the spinal cord lesion. The
      increased proviral load in FA suggests the existence of genetic factors
      contributing to the replication of HTLV-I in vivo.

PMID- 10065901
TI  - Localization of mouse hepatitis virus open reading frame 1A derived proteins.
AB  - We have investigated the intracellular localization of proteolytic cleavage
      products encoded in the 5' portion of mouse hepatitis virus (MHV) gene 1.
      Immunofluorescent labeling of cells with an antiserum which recognizes p28, the
      ORF1a N-terminal cleavage product, resulted in widespread somewhat granular
      cytoplasmic staining, indicating that this protein is widely distributed in the
      cytoplasm of MHV-infected, but not control uninfected cells. Immunofluorescent
      staining of infected cells with antisera which recognize the downstream
      polypeptides, p65, p240 and p290 labeled discrete vesicular perinuclear
      structures. Double immunofluorescent labeling of BHK cells expressing the MHV
      receptor (BHK(MHVR1)) and infected with MHV-A59 with a Golgi-specific anti
      mannosidase II monoclonal antibody and with antiserum recognizing each of these
      anti-MHV ORF1a polypeptides, showed that the p240 and p290 polypeptides were
      localized in discrete vesicular structures that overlapped the Golgi complex.
      Labeling with antibodies specific for p65 colocalized with the Golgi region, and
      showed staining of the perinuclear cytoplasm as well. Plasmids containing
      sequences contained in the first 6.75 kb of ORF1a have been expressed using the
      coupled vaccinia virus-T7 polymerase system. Immunofluorescent labeling of
      transfectants with the anti-ORF1a antisera showed patterns of antigen
      distribution similar to those observed in cells infected with MHV-A59. A deletion
      analysis with constructs containing only portions of the ORF1a sequence indicated
      that 303 amino acids containing the first papain-like protease domain (PLP-1) was
      sufficient to associate this protein with the Golgi.

PMID- 10065902
TI  - Regional changes in 5-HT1A but not in 5-HT2A receptors in mouse brain after
      Semliki Forest virus infection: radioligand binding and autoradiographic studies.
AB  - Dysfunction of brain 5-hydroxytryptaminergic systems has been associated with
      several neurological and psychiatric diseases which may have a viral aetiology.
      The effect of Semliki Forest virus (SFV) on 5-hydroxytryptamine (5-HT1A and 5
      HT2A) receptors in mouse brain has been assessed by membrane homogenate binding
      and autoradiography. Adult mice were injected with saline or virus and brains
      removed 2, 6, 14, 22 and 35 days after infection. 5-HT1A and 5-HT2A receptors
      were characterised by saturation studies using [3H] 8-OH-DPAT and [3H] Ketanserin
      respectively. SFV infection increased 5-HT1A receptor numbers by up to 80% in the
      cortex on days 6, 14, and 22 but had no effect on Bmax in the midbrain,
      pons/medulla and the hypothalamus. SFV infection did not affect 5-HT2A receptor
      number in any of the brain regions studied and the affinity (Kd) of either ligand
      for 5-HT1A or 5-HT2A receptors was unaffected. Autoradiographic mapping of 5-HT1A
      receptors in SFV-infected brain showed substantially higher binding in nucleus
      accumbens, tenia tecta, septohippocampal nucleus, septum, medial and basolateral
      amygdaloid nucleus, anterioventral preoptic nucleus, hippocampus, interpeduncular
      nucleus, frontal, lateral orbital, and entorhinal cortex and claustrum on days 6
      and 14. Elevated binding persisted in tenia tecta, frontal, lateral orbital,
      entorhinal cortex, and hippocampal formation to day 22. Autoradiography of 5-HT2A
      receptors using [3H] Ketanserin showed no difference in the binding in SFV
      infected brains. A decrease in plasma corticosterone levels in SFV-infected mice
      was observed on post infection days 6 and 22. These results show SFV infection
      induces a regionally selective upregulation of 5-HT1A but not 5-HT2A receptors.

PMID- 10065903
TI  - Cocaine opens the blood-brain barrier to HIV-1 invasion.
AB  - Cocaine abuse has been associated with vasculitis and stroke, and is suspected to
      influence the progression of AIDS dementia. Cocaine may enhance HIV-1
      neuroinvasion by actions directed at the blood-brain barrier. HIV-1 appears to
      penetrate the human brain microvascular endothelial cell barrier by a
      paracellular route breached by tumor necrosis factor-alpha (TNF-alpha). Cocaine's
      effects on the blood-brain barrier were investigated using human brain
      microvascular endothelial cells and peripheral blood monocytes. Cocaine (10(-5) M
      and 10(-6) M) increased molecular permeability of the barrier and viral invasion
      by the macrophage-tropic HIV-1(JR-FL) into the brain chamber. Cocaine also
      augmented apoptosis of brain endothelial cells and monocytes, increased secretion
      of four chemokines (interleukin-8, interferon-inducible protein-10, macrophage
      inflammatory protein-1alpha, and monocyte chemoattractant protein-1) and the
      cytokine, TNF-alpha, by human monocytes. TNF-alpha enhanced invasion of the brain
      compartment by macrophage-tropic, lymphotropic, and bitropic HIV-1 strains. These
      data indicate that HIV-1 neuroinvasion can be increased by (a) cocaine's direct
      effects on brain microvascular endothelial cells and (b) paracrine effects of
      cocaine-induced pro-inflammatory cytokines and chemokines on the blood-brain
      barrier.

PMID- 10065904
TI  - Effect of bafilomycin A1 on the growth of Japanese encephalitis virus in Vero
      cells.
AB  - We studied the effect of bafilomycin A1 (Baf-A1), a novel and highly specific
      inhibitor for vacuolar-type proton (V-H+) pump, on the growth of Japanese
      Encephalitis virus (JEV) in Vero cells. Viral fluorescence microscopic study
      showed that Baf-A1 induced the complete disappearance of acidified compartments
      such as endosomes and lysosomes in Vero cells by the treatment with 0.1 microM
      Baf-A1 for 1 h at 37 degrees C. In proportion to the disappearance of acidified
      compartments, virus growth was inhibited when Baf-A1 was present from 1 h before
      infection to the end of incubation in a dose-dependent manner, or added within as
      early as 5 min after infection. Conversely, the virus growth was recovered in
      correlation with the reappearance of acidified compartments after removal of Baf
      A1. These results suggest that a low pH condition, which is regulated by Baf-A1
      sensitive V-H+ pumps, is essential for the early stage of JEV growth.

PMID- 10065905
TI  - Antipsychotic drugs for non-psychotic patients: assessment of the benefit/risk
      ratio in generalized anxiety disorder.
AB  - Antipsychotic drugs (neuroleptics, major tranquillizers) are frequently
      prescribed for the relief of anxiety symptoms. A recent survey of a
      representative sample of psychiatrists found that these drugs are often given to
      patients who are not suffering from psychotic disorders, a practice that also
      appears to be common among general practitioners. Many authors have commented on
      the value of antipsychotics in relieving anxiety symptoms, both in the short and
      long term, as an alternative to benzodiazepines (with their associated risk of
      possible tolerance and dependence), although few recent papers recommend their
      use in this respect. This paper summarizes the evidence from treatment studies of
      antipsychotic drugs in patients with generalized anxiety disorder (GAD), and
      compares this with the advice given in major psychiatric textbooks. Most of the
      studies identified on the use of antipsychotic drugs in GADs appear to have major
      methodological flaws, and no study has considered the benefit/risk ratio
      carefully.

PMID- 10065906
TI  - Repeated testing of prepulse inhibition and habituation of the startle reflex: a
      study in healthy human controls.
AB  - The aim of this study was to examine the effect of repeated testing on prepulse
      inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control
      subjects (eight males, mean age 30 years; seven females, mean age 29 years) were
      tested on three occasions across the same day separated by a minimum of 2 h. An
      acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous
      background noise of 70 dB(A) was presented binaurally through headphones and the
      eye-blink component of the startle response was measured taking electromyographic
      recordings from the right orbicularis oculi. The test session was identical at
      each time point and consisted of two blocks of 12 randomly mixed trials of four
      pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by
      two blocks each of six pulse-alone trials. There was huge variation in individual
      response magnitude that was independent of subsequent PPI in both women and men.
      Women showed greater PPI in the second half of sessions with the 120-msec
      prepulse only; but PPI was not altered significantly in either group between
      sessions across the day. In general, there was good test-retest reliability of
      PPI especially within trial type. Normal reflex habituation occurred across
      sessions and this effect was preserved in sessions across the day. Latency of
      response was significantly reduced in a session by the 60-msec trial type
      compared to the 120-msec trial type, as previously reported. Our results suggest
      that measures of PPI and habituation of the startle response are appropriate and
      reliable for a within-subject, test-retest design.

PMID- 10065907
TI  - An examination of differences in the time course of oxazepam's effects on
      implicit vs explicit memory.
AB  - The present study was designed to examine the effects of oxazepam on implicit vs
      explicit memory processes, as a function of this drug's time course. The effects
      of oxazepam (30 mg) or placebo on directly comparable tests of implicit memory
      (word stem completion) and explicit memory (cued recall) were examined at three
      time points: 100 min post-drug administration (prior to the theoretical peak
      plasma concentration of oxazepam; i.e.'pre-peak' condition), 170 min post-drug
      (close to theoretical peak; i.e. 'peak' condition) or 240 min post-drug
      (following theoretical peak: i.e. 'post-peak' condition). Sixty healthy
      volunteers were randomly assigned to either the drug condition or the placebo
      condition in a double-blind design and were tested on both memory tests at one of
      the three time points. In the 'pre-peak' condition, oxazepam impaired cued recall
      performance relative to placebo but did not impair priming. In the 'peak'
      condition, oxazepam impaired performance on both memory tasks. In the 'post-peak'
      condition, cued recall performance in the oxazepam group remained significantly
      impaired relative to placebo. However, oxazepam-induced impairments in priming
      were only marginal, suggesting that oxazepam-induced impairments in implicit
      memory processes begin to wane following theoretical peak drug concentrations.
      The fact that oxazepam-induced priming impairments were significant only when the
      word stem completion task was administered close to peak plasma concentrations,
      supports the hypothesis that benzodiazepines exert time-dependent effects on
      implicit memory processes. The results also support the theoretical distinction
      between implicit and explicit memory processes, since the directly comparable
      implicit and explicit tasks showed different impairment curves over time.

PMID- 10065908
TI  - Psychopharmacological profile of the selective serotonin reuptake inhibitor,
      paroxetine: implication of noradrenergic and serotonergic mechanisms.
AB  - The present study was designed to evaluate the psychopharmacological profile of
      the selective serotonin reuptake inhibitor paroxetine, and thus assess potential
      noradrenergic and/or serotonergic activity. Paroxetine dose-dependently increased
      mobility time in the mouse forced swimming test (8, 16, 32 and 64 mg/kg, i.p.)
      and reduced spontaneous locomotor activity when administered at a high dose (64
      mg/kg, i.p.). Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (1
      mg/kg, i.p.), (+/-) pindolol (32 mg/kg, i.p.) or 5-methoxy-3-(1,2,3,6-tetrahydro
      4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.) potentiated the antidepressant
      like effects of subactive doses of paroxetine (1, 2 and 4 mg/kg, i.p.) in the
      mouse forced swimming test. These effects were antagonized by prior
      administration of 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (0.5
      mg/kg, i.p.). Complementary studies suggested that RU24969-induced anti
      immobility effects were a result of an increase in locomotor activity; other
      interactions were without increase/decrease in locomotor activity. Acute
      administration of paroxetine (8, 16, and 32 mg/kg, i.p.) antagonized the
      hypothermia induced by the D2/D1 receptor agonist, apomorphine (16 mg/kg, s.c.),
      while repeated treatment with paroxetine (32 mg/kg) attenuated clonidine-induced
      (0.5 mg/kg, i.p.) hypothermia. Pre-treatment with the serotonergic neurotoxin,
      para-chlorophenylalanine attenuated the anti-immobility effects of low doses of
      paroxetine (8 and 16 mg/kg, i.p.) in the forced swimming test, whereas a higher
      dose of paroxetine remained active (32 mg/kg, i.p.). The results of the present
      study indicated that paroxetine displayed both noradrenergic-like and
      serotonergic-like activity in the pre-clinical psychopharmacological tests
      employed.

PMID- 10065909
TI  - Limited anxiolytic-like effects of non-benzodiazepine hypnotics in rodents.
AB  - The present experiments compared the anxiolytic-like effects of the
      benzodiazepine (BZD) hypnotic triazolam with those of four non-BZD hypnotics
      including one non-selective (zopiclone) and three omega1-BZD selective (zolpidem,
      zaleplon and SX-3228) receptor ligands, in classical animal models including
      conflict tests (punished lever pressing and punished drinking tests in rats) and
      exploratory models (elevated plus-maze test in rats and light/dark choice test in
      mice), and a recently developed mouse defence test battery (MDTB) which has been
      validated for the screening of anxiolytic drugs. Results from both conflict
      procedures showed that zopiclone (0.3-10 mg/kg) produced anxiolytic-like effects
      comparable to those of triazolam (0.1-3 mg/kg), whereas the selective omega1-BZD
      receptor hypnotics zolpidem (0.3-3 mg/kg), zaleplon (0.1-3 mg/kg) and SX-3228
      (0.1-1 mg/kg) displayed weaker and/or non-specific anxiolytic-like effects.
      Similarly, in the light/dark test in mice, zolpidem (0.1-1 mg/kg), zaleplon (0.3
      10 mg/kg) and SX-3228 (0.03-0.3 mg/kg) showed a reduced potential to produce
      anxiolytic-like effects as compared to the non-selective omega-BZD receptor
      hypnotics triazolam (0.03-1 mg/kg) and zopiclone (1-30 mg/kg). In the elevated
      plus-maze test, zopiclone (1-10 mg/kg), zolpidem (0.1-1 mg/kg), zaleplon (0.3-3
      mg/kg) and SX-3228 (0.1-1 mg/kg) displayed anxiolytic-like activity at doses
      close to those producing behavioural impairment, whereas triazolam (0.03-1 mg/kg)
      exhibited anxiolytic-like effects over a wide dose range in the absence of
      decreases in general activity. In the MDTB, zaleplon (0.3-10 mg/kg) decreased all
      defensive responses, a profile which was similar to that of triazolam (0.03-1
      mg/kg), while zopiclone (1-30 mg/kg), zolpidem (0.3-10 mg/kg) and SX-3228 (0.03-1
      mg/kg) had fewer effects on defensive behaviours with several effects occurring
      only at motor-impairing doses. Taken together, these results demonstrate that,
      although selective omega1-BZD receptor hypnotics display anxiolytic-like
      activity, the effects are generally weaker than those observed with non-selective
      omega-BZD receptor selective hypnotics such as triazolam or zopiclone. In
      particular, the anxiety-reducing potential of the omega1-BZD receptor selective
      compounds is limited to certain anxiety measures and may be confounded and/or
      masked by behavioural suppression.

PMID- 10065910
TI  - Sertraline, a selective serotonin reuptake inhibitor modulates extracellular
      noradrenaline in the rat frontal cortex.
AB  - The selective action of selective serotonergic reuptake inhibitors (SSRIs) on 5
      hydroxytryptamine (5-HT) neurotransmission underlies the therapeutic
      effectiveness of this class of drugs. Yet there is increasing evidence that
      changes in extracellular 5-HT content may result in changes in the regulation of
      other neurotransmitter systems. The present study examines the effects of acute
      and chronic administration of the SSRI sertraline on release of endogenous
      noradrenaline (NA) in the frontal cortex and hippocampus of the rat using in vivo
      microdialysis. Acute administration of sertraline did not significantly alter NA
      release in either the cortex or the hippocampus. However, 24 h after chronic (14
      days) administration of the drug (10 mg/kg i.p. once daily), NA release in the
      cortex but not hippocampus was significantly enhanced. The lack of an effect on
      NA release following a challenge with the alpha2-antagonist idazoxan suggests
      that chronic drug treatment has reduced the sensitivity of cortical pre-synaptic
      alpha2-adrenoceptors, activation of which would normally inhibit further NA
      release. The possible mechanisms underlying the regional specificity of the
      effect of chronic and not acute sertraline administration and the implications of
      these results for our understanding of depression are discussed.

PMID- 10065911
TI  - Effect of venlafaxine on pineal melatonin and noradrenaline in the male rat.
AB  - Studies in vitro indicate that the antidepressant drug, venlafaxine (VEN),
      inhibits the reuptake of both serotonin (5-hydroxytryptamine, 5-HT) and
      noradrenaline (NA) but has little activity on other neurotransmitter receptors.
      There are, however, few studies on the effects of VEN on monoamine
      neurotransmission in vivo. In the present study we examined the effect of VEN
      treatment on the melatonin content of the rat pineal gland because the synthesis
      of melatonin is regulated by the release of NA onto pinealocyte beta
      adrenoceptors. Acute treatment with higher doses (15 mg/kg) of VEN significantly
      increased pineal melatonin and NA but this effect was attenuated by subchronic
      treatment. These data are consistent with in vitro data suggesting that VEN
      increases NA neurotransmission at higher doses and that repeated treatment can
      desensitize pinealocyte beta-adrenoceptors.

PMID- 10065912
TI  - Nicotine-induced grooming: a possible dopaminergic and/or cholinergic mechanism.
AB  - The ability of nicotine, to induce grooming in rats was studied. Grooming was
      induced by i.p. injection of different doses (0.0675-0.5 mg/kg) of nicotine to
      rats. The effect was dose-dependent. However, the response was decreased with
      increasing doses of the drug from 0.25-0.5 mg/kg. Administration of the dopamine
      (DA) D1/D2 receptor agonist apomorphine (0.025-5 mg/kg, i.p.) also caused
      grooming in a dose-dependent manner. High doses of apomorphine (0.1-0.5 mg/kg,
      i.p.) also induced a lower degree of response. Combination of a low dose of
      nicotine (0.0675 mg/kg) with different doses of apomorphine did not show any
      interaction. However, there was an interaction between a high dose of nicotine
      and apomorphine. Thus, combination of a higher dose of nicotine (0.125 mg/kg)
      with apomorphine, reduced apomorphine-induced grooming. The muscarinic receptor
      antagonist atropine (5 and 10 mg/kg), peripheral nicotinic receptor antagonist
      hexamethonium (5 and 10 mg/kg), central nicotinic receptor antagonist
      mecamylamine (1 and 3 mg/kg) and D1 DA receptor antagonist SCH23390 (0.05 and 0.1
      mg/kg) all decreased the response to nicotine. Atropine, mecamylamine and
      SCH23390 by themselves reduced spontaneous grooming. It is concluded that
      nicotine elicits grooming indirectly through a possible D1 dopaminergic
      mechanism. However, muscarinic and nicotinic cholinergic mechanism(s) may be
      involved.

PMID- 10065913
TI  - The novel buspirone analogue, 8-[4-[2-(1,2,3,4-tetrahydroisoquinolinyl)[butyl]-8
      azaspiro [4.5 ]decane-7,9-dione, with anxiolytic-like and antidepressant-like
      effects in rats.
AB  - In the conflict drinking test, used as a model to examine anxiolytic-like
      activity, the novel buspirone analogue 8-[4-[2-(1,2,3,4
      tetrahydroisoquinolinyl)]butyl)-8-azaspiro[ 4.5]decane-7,9-dione (MM199) (0.62
      2.5 mg/kg) and buspirone (0.62-5 mg/kg), significantly increased the punished
      drinking in water-deprived rats, without affecting water consumption or
      perception of the stimulus. The anticonflict activity of MM199 (1.25 mg/kg) was
      blocked by (S)-WAY 100135 (20 mg/kg), a 5-hydroxytrypatmine1A (5-HT1A) receptor
      antagonist. In the forced swimming test, used as a model to examine the
      antidepressant-like activity, MM199 (5-20 mg/kg) reduced the immobility time,
      while buspirone (5-20 mg/kg) had no such effect. The reduced immobility induced
      by MM199 (20 mg/kg) was antagonized by (S)-WAY100135 (10 mg/kg). The above
      findings suggest that MM199 possesses potent anxiolytic- and antidepressant-like
      properties which are mediated by activation of 5-HT1A receptors.

PMID- 10065914
TI  - Pharmacotherapy of adolescent attention deficit hyperactivity disorder:
      challenges, choices and caveats.
AB  - A recent increase in stimulant treatment of adolescents with attention deficit
      hyperactivity disorder (ADHD) has been documented. Challenges in treating
      adolescent ADHD with methylphenidate or dextroamphetamine include compliance with
      frequent dosing, abuse potential and wear-off or rebound effects. Co-morbid
      anxiety, occurring in at least 30 percent of ADHD youths, is associated with
      lower rate of response to stimulants. The effective alternatives, tricyclic
      antidepressants or pemoline, are each associated with rare but serious toxicity.
      Bupropion has recently proven effective in controlled trials. Other noradrenergic
      or dopamine-enhancing agents such as venlafaxine and nicotine show some benefit
      in open trials. The need for more options in pharmacotherapy of ADHD is evidenced
      by rapid adoption in clinical practice of alternative and adjunctive medication
      despite lack of controlled research on efficacy and safety. The indications for
      long-term stimulant treatment of ADHD present some controversy, and highlight a
      need for more research on safety and efficacy through the lifespan. Thresholds
      for diagnosis are much lower with DSM than with ICD, and thresholds for treatment
      are contentious, given the performance-enhancing effects of stimulants in normal
      students. The endpoint for treatment is unclear, as stimulants are also effective
      in adult ADHD. Based on short- and intermediate-term studies to date, stimulant
      medication is clearly more efficacious than cognitive and behavioral strategies
      for the symptoms of ADHD. Longer term research is needed to determine whether
      sustained stimulant therapy will reduce the adverse emotional, behavioral and
      academic consequences of inattention and impulsivity in adolescents and adults.

PMID- 10065915
TI  - Selective serotonin reuptake inhibitors and hyponatraemia: review and proposed
      mechanisms in the elderly.
AB  - The association between selective serotonin reuptake inhibitors (SSRIs) and
      hyponatraemia has been well documented, the elderly appearing to be at greatest
      risk. An analysis of data of hyponatraemia in the elderly using SSRIs from all
      published cases and from the Committee on Safety of Medicines found that the mean
      time to detection was about 3 weeks after commencing SSRIs. A wide range of time
      to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is
      detected by chance rather than being specifically looked for. In the elderly
      there are physiological changes, a high prevalence of medical illnesses and
      concomitant drug use, which may precipitate hyponatraemia. Together with a risk
      of altered water regulation in psychiatric illness this may account for the
      particular susceptibility of the elderly to hyponatraemia whilst using SSRIs.

PMID- 10065916
TI  - Neuroleptic discontinuation syndromes.
AB  - The existence of discontinuation syndromes following treatment with neuroleptic
      (antipsychotic) drugs was first outlined in the mid-1960s but the effects of such
      syndromes have been neglected since then. We have pursued evidence for the
      existence and nature of discontinuation syndromes following neuroleptics through
      reports of difficulties following the use of dopamine blocking anti-emetics, the
      use of chlorpromazine to treat tuberculosis, the use of antidepressant
      neuroleptic combinations in affective disorders, the occurrence of tardive
      syndromes and studies designed to establish the existence of discontinuation
      syndromes in schizophrenia. Combined these bodies of data point strongly to the
      existence of discontinuation syndromes after cessation of treatment with
      neuroleptics which may involve features other than motor dyskinesias. There is at
      present little evidence on the relative frequency of such syndromes or
      predisposing factors. The area needs research input to establish the nature of
      the syndromes that may result, their frequency, predisposing factors and best
      methods of treatment.

PMID- 10065917
TI  - The analgesic effects of selective serotonin reuptake inhibitors.
AB  - This paper endeavours to provide a critical clinical review of the use of
      selective serotonin reuptake inhibitors (SSRIs) in the management of pain. Case
      reports, placebo-controlled trials and trials comparing SSRIs with tricyclic
      antidepressants (TCAs) are considered. The analgesic effects of TCAs are well
      known and this review suggests that there is little evidence for their
      replacement by SSRIs in pain management. There are, at present, too few
      comparative drug trials to make a definitive statement, although the trend is
      clearly against SSRIs.

PMID- 10065918
TI  - Enhanced appetitive conditioning following repeated pretreatment with d
      amphetamine.
AB  - The behavioural response to psychomotor stimulants is augmented with repeated
      exposure to these drugs. Enhanced stimulated dopamine overflow within the nucleus
      accumbens and amygdala has been found to accompany this behavioural
      sensitization. In the present experiment, rats received 2 mg/kg d-amphetamine or
      1 ml/kg physiological saline once per day for 5 days. Five days later, a
      behavioural assay confirmed that prior repeated d-amphetamine treatment markedly
      enhanced the locomotor activating effects of a d-amphetamine (0.5 mg/kg, i.p.)
      challenge. Training on a Pavlovian conditioning task began six days subsequently.
      In Stage 1, a stimulus (light or tone, S-) was presented negatively correlated
      with a sucrose reward. In Stage 2, presentation of the alternative
      counterbalanced stimulus (light or tone, S+) was paired with the availability of
      a 10% sucrose solution. There were no differences between the two groups in their
      response to the the S- stimulus. However, sensitized animals showed a selective
      enhancement in the acquisition of conditioned responding to S+, relative to
      vehicle-injected controls. No differences in behaviour were recorded during the
      prestimulus periods, nor during presentations of sucrose. Levels of activity
      within the operant chamber extraneous to alcove approach were also similar in
      both groups of animals. The conditioned instrumental efficacy of S+, relative to
      S- was assessed in Stage 3, in which stimulus availability was made contingent on
      a novel lever-pressing response. Both groups showed a similar preference for the
      S+ over the S- stimulus. Hence, rats sensitized by prior repeated d-amphetamine
      showed enhanced appetitive Pavlovian conditioning, without subsequent effect on
      conditioned reward efficacy. These data are discussed in light of possible
      changes in mesoamygdaloid dopamine functioning.

PMID- 10065919
TI  - Antidepressant-like effects of 5-hydroxytryptamine1A receptor agonists on operant
      responding under a response duration differentiation schedule.
AB  - A response duration differentiation schedule, where rats depress a lever for
      between 1.0 and 1.3 s to obtain a food reward, provides a useful measure for
      detecting antidepressant activity. It is known that 5-hydroxytryptamine1A (5
      HT1A) receptor agonists exhibit antidepressant-like activity in multiple animal
      models of depression, however, compounds selective for this receptor have not
      been tested in this model to date. Thus, the present study sought to determine
      the effect of the full 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8
      OH-DPAT) and the partial 5-HT1A agonist, buspirone, on responding in the response
      duration differentiation task. The effects of these drugs were compared to the
      effects of the non-specific serotonergic agonist, lysergic acid diethylamide
      (LSD); the phenothiazine, chlorpromazine; the atypical antidepressant, trazodone;
      and the non-selective 5-HT1A antagonists, propranolol and alprenolol. It was
      found that propranolol, trazodone, and both the full (8-OH-DPAT) and partial
      (buspirone) 5-HT1A agonists produced increases in the mean response duration,
      which is typical of antidepressant activity. By contrast, with the exception of
      propranolol, compounds lacking antidepressant efficacy (e.g. chlorpromazine, LSD
      and alprenolol), failed to produce increases in mean response durations. Further,
      the effects of 8-OH-DPAT were inhibited by pretreatment with the 5-HT1A
      antagonist, (-)-alprenolol (3.0 and 30.0 mg/kg i.p.). The results of this study
      provide further support for the suggestion that 5-HT1A agonists may be useful for
      the treatment of clinical depression and that these effects are specifically
      mediated by 5-HT1A receptors.

PMID- 10065920
TI  - Delta opioid-like discriminative stimulus effects of mu opioids in pigeons
      discriminating the delta opioid BW373U86 from saline.
AB  - The purpose of this experiment was to examine the substitution patterns produced
      by opioids with activity at the mu receptor in pigeons trained to discriminate
      the delta opioid BW373U86 from saline. A low dose of naltrindole (0.1 mg/kg)
      produced at least a 16-fold rightward shift in the dose-effect curve for the
      stimulus effects of BW373U86 (yielding a pK(B) = 7.9), whereas a relatively high
      dose of naloxone (1.0 mg/kg) produced only a 2-fold rightward shift (yielding a
      pK(B) = 5.6). The delta opioid SNC80 and the mixed mu/kappa opioids
      ethylketocyclazocine and ketocyclazocine substituted completely for the BW373U86
      stimulus. Various opioids with activity at the mu receptor (levallorphan, [-]
      cyclazocine, [-]-n-allylnormetazocine, morphine, butorphanol, nalbuphine, [+]
      propoxyphene, etorphine, fentanyl) substituted partially for the BW373U86
      stimulus. There was no relationship between the substitution patterns produced by
      these opioids and their relative intrinsic efficacy at the mu receptor, their
      relative selectivity for the mu receptor or their relative affinity for the delta
      receptor. Naloxone (1.0 mg/kg) was considerably more effective than naltrindole
      (0.1 mg/kg) in antagonizing the substitution patterns produced by etorphine,
      ethylketocyclazocine, ketocyclazocine and butorphanol, suggesting that these
      effects were not mediated by activity at the delta receptor. There was no
      evidence that these opioids antagonized the BW373U86 stimulus, suggesting that
      they were not functioning as low efficacy agonists at the delta receptor. The
      kappa opioids bremazocine and U50,488, as well as the non-opioids cocaine and
      pentobarbital, failed to produce appreciable levels of BW373U86 responding. The
      present findings indicate that in pigeons mu opioids most likely produce delta
      like discriminative stimulus effects by activation of mu rather than delta or
      kappa receptors.

PMID- 10065921
TI  - Discriminative stimulus effects of self-administered ethanol.
AB  - The conditions under which a drug is administered often alter the behavioral
      effects of that drug. The present study examined the effect of changes in
      response dependence on the discriminative stimulus effects of ethanol. Six Long
      Evans rats were trained to discriminate 1000 mg/kg, interperitoneal (i.p.)
      ethanol from saline. A dose-effect curve was then obtained using i.p. doses of
      100, 320, 560, 1000, 1320 and 1560 mg/kg ethanol. Ethanol doses of 1000 mg/kg and
      greater produced more than 80% ethanol-lever selection. The rats were then
      trained to orally self-administer 10% weight/volume ethanol and tested to
      determine if self-administered oral ethanol would substitute for experimenter
      administered i.p. ethanol. A mean self-administered ethanol intake of 1114 mg/kg
      (+/-156 mg/kg) produced 83% ethanol-lever responding. Restricted access to 560
      mg/kg of self-administered ethanol resulted in 33% i.p. ethanol-lever responding.
      Doses of 100 and 320 mg/kg ethanol did not substitute for i.p. ethanol. These
      data show that orally self-administered ethanol can produce discriminative
      stimulus effects that are similar to i.p. experimenter-administered ethanol and
      that orally self-administered ethanol produces centrally-mediated discriminative
      stimulus effects.

PMID- 10065922
TI  - Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in the generalization of 5-HT
      receptor agonists to the ethanol cue in the rat.
AB  - Although accumulating evidence suggests that serotonergic drugs are able to
      substitute for the ethanol (EtOH) cue in rats, it is still unclear which 5-HT
      receptor subtypes are responsible for this phenomenon, and whether these
      receptors are critically involved in the EtOH cue. In the present study, rats
      were trained to discriminate EtOH (1000 mg/kg, i.p., t-15 min) from saline in a
      two-lever food-reinforced procedure, and it was investigated to which extent
      serotonergic compounds with a certain level of specificity for either 5-HT1B, 5
      HT2A or 5-HT2C receptors generalized to the EtOH cue. Subsequently, the
      involvement of these receptor subtypes was ascertained by the use of selected 5
      HT receptor antagonists. The 5-HT1B receptor agonist CP 94,253 (0.3-5 mg/kg,
      i.p.) and the mixed 5-HT(2C/1B) receptor agonist mCPP (0.1-1 mg/kg, i.p.), but
      not the preferential 5-HT2A receptor agonist DOI (0.3-1 mg/kg, i.p.), completely
      generalized to the EtOH cue. Complete generalization of the former two compounds
      coincided with a decrease in response rate. In antagonism studies, it was shown
      that the 5-HT1B receptor antagonist GR 127935 (10 mg/kg, i.p.) completely blocked
      generalization of CP 94,253 to the EtOH cue, suggesting that stimulation of 5
      HT1B receptors produces discriminative stimulus effects which are similar to
      those of EtOH. GR 127935 (10 mg/kg, i.p.), as well as the mixed 5-HT(1B/2C)
      receptor antagonist metergoline (1 mg/kg, i.p.), and the 5-HT2C receptor
      antagonist SB 206,553 (1 mg/kg, i.p.) completely blocked generalization of mCPP
      to the EtOH cue. This suggests that 5-HT1B and 5-HT2C receptors are required for
      the generalization of mCPP to the EtOH cue. The present findings indicate that
      activation of 5-HT1B and 5-HT2C, but not of 5-HT2A receptors, mimics the EtOH
      cue. However, the finding that neither metergoline, nor the 5-HT2A receptor
      antagonist MDL 100,907 blocked the EtOH cue, suggests that these receptors play
      only a minor role in the discriminative stimulus effects of a moderately low dose
      of EtOH.

PMID- 10065923
TI  - Interactions between sulpiride infusions within the perifornical region of the
      lateral hypothalamus and the nucleus accumbens on measures of locomotor activity
      and conditioned place preference.
AB  - There is growing evidence of a functionally significant link between the
      perifornical region of the lateral hypothalamus (PFH) and the mesoaccumbens
      dopamine projection. The present study assessed the ability of intra-accumbens
      dopamine receptor blockade, firstly to impair the locomotor stimulant properties
      of intra-PFH sulpiride, and secondly the ability of intra-PFH sulpiride to
      support a conditioned place preference. Locomotor activity and conditioned place
      preference training were assessed using an apparatus consisting of three
      distinctive compartments. Following a pre-exposure session in which groups showed
      equivalent preference for the three compartments, conditioned place preference
      training was carried out over five drug (0, 0.03 or 0.1 microg intra-accumbens
      sulpiride; 0 or 5 microg intra-PFH sulpiride) and five vehicle sessions. For each
      animal, drug and vehicle treatments were randomly paired with one of the two
      outermost compartments. Locomotor activity was monitored during each session.
      Intra-PFH sulpiride alone increased locomotor activity during later sessions, and
      this gradual increase in locomotor response, relative to vehicle infusions, was
      blocked by intra-accumbens sulpiride co-infusion. On the final drug-free test day
      for conditioned place preference, animals were again permitted free access to all
      three compartments, and the time spent in each was compared with that on initial
      exposure. Intra-PFH sulpiride alone supported a conditioned place preference.
      Intra-accumbens sulpiride was without intrinsic effect, but nevertheless blocked
      the ability of intra-PFH sulpiride to support a conditioned place preference.
      These data provide further support for a functionally significant link between
      the PFH and mesoaccumbens dopamine projection, with regard to the locomotor
      stimulant properties and ability of intra-PFH infusions of sulpiride to support a
      conditioned place preference.

PMID- 10065924
TI  - Reinforcement frequency, but not gender, determines sensitivity to discriminative
      stimulus effects of morphine.
AB  - We demonstrated previously that several parameters of a morphine discrimination
      were significantly different in female versus male rats, using a fixed ratio (FR)
      10 schedule of food reinforcement; however, this schedule produced a significant
      bias in reinforcement frequency between saline and morphine sessions in males but
      not in females. To determine whether this schedule-drug-sex interaction caused
      the sex difference in discriminability of morphine, female and male rats were
      trained to discriminate 3.0 mg/kg morphine from saline using a variable interval
      (VI) 15-s/VI 15-s (Phase I), a VI 7.5-s/VI 15-s (Phase II), and a VI 15-s/VI 15-s
      (Phase III) schedule of food reinforcement on morphine/saline levers,
      respectively. After a minimum of 40 training sessions in each phase, mean
      reinforcement rates in morphine sessions were highest, and the ED50 values for
      morphine discrimination were lowest, in Phase II. Thus, as predicted, the
      morphine dose-effect curves shifted to the left from Phase I to Phase II, and
      back to the right from Phase II to III, presumably due to the bias in
      reinforcement rate between saline and morphine sessions that was induced by
      manipulating the VI schedule on the morphine lever. However, there were no sex
      differences in the morphine versus saline reinforcement rate or in discrimination
      ED50 in any phase, suggesting that the sex difference observed in our initial
      study was probably due to the bias in reinforcement frequency (towards the saline
      condition) that occurred only in males under the FR-10 schedule. This study
      demonstrates the importance of considering group differences in schedule-drug
      interactions when comparing discriminative stimulus properties of drugs between
      groups.

PMID- 10065925
TI  - Ethanol drinking in socially housed squirrel monkeys.
AB  - This study proposes a method to assess voluntary alcohol drinking in socially
      living squirrel monkeys. Group-housed squirrel monkeys were induced to drink a
      sucrose solution and subsequently an ethanol/sucrose solution in an experimental
      chamber attached to the home colony room, allowing the daily intake to be
      monitored for each individual without disrupting the social context. Sucrose
      concentration (0.03-0.6 M, corresponding to 1-20%) and ethanol concentration (0
      4%) were gradually increased in tap water and in a 0.6 M (ca. 20%) sucrose
      solution during daily 30-min and 10-min sessions, respectively. Blood ethanol
      levels ranged from 10-50 mg/dl and remained below intoxication level. These
      experiments demonstrate that it is feasible to arrange conditions under which
      individual socially housed squirrel monkeys voluntarily drink a sweetened ethanol
      solution.

PMID- 10065926
TI  - Kin interaction enhances morphine analgesia in male mice.
AB  - The additive effect of social and pharmacological treatments was evaluated in
      pairs of male mice. Ineffective and effective doses of morphine (2.5 and 5.0
      mg/kg, i.p.) were tested on pain threshold in dyads of males at different times
      after pair formation and drug treatment. During the second hour of social
      interaction after reunion, saline-injected adult sibling male mice showed a
      decrease in nociception as measured by the tail-flick test. Pairs of unrelated,
      unfamiliar control mice showed no changes in pain sensitivity during a 2-h social
      session. An ineffective dose of 2.5 mg/kg of morphine in non-sibling males,
      significantly increased tail-flick latencies in sibling pairs, before the effect
      of the social environment (sibling) reached statistical significance. The higher
      dose of morphine (5.0 mg/kg) produced analgesia in sibling as well as in non
      sibling males, but the effect in the latter disappeared 60 min after drug
      treatment, whereas siblings were still analgesic. These results indicate that an
      ineffective dose of morphine, combined with the activation of the endogenous
      opioid system by social factors, can affect nociception.

PMID- 10065927
TI  - Is barakol anxiolytic?
AB  - A recent report suggested that barakol, a biologically active extract of the
      south-east Asian plant, Cassia siamea, has anxiolytic properties. The purpose of
      the present study was to replicate and extend these findings by examining the
      dose-response effects of barakol (0-20 mg/kg) in two pharmacologically validated
      tests of rat anxiety: the elevated plus-maze and the shock-probe burying tests.
      Although the purity of our sample of barakol was confirmed by chemical analysis,
      we found no evidence of its anxiolytic effects in either the plus-maze or shock
      probe burying tests.

PMID- 10065928
TI  - Discriminative stimulus effects of benzodiazepine agonists and partial agonists
      in pentobarbital-trained rhesus monkeys.
AB  - The present study examined the relationship between the intrinsic efficacy of
      benzodiazepines and their ability to reproduce the discriminative stimulus
      effects of pentobarbital. Rhesus monkeys (n=5) were trained to discriminate
      pentobarbital (10mg/kg) from saline using a discrete trials shock avoidance
      procedure (fixed-ratio 5). Drug-appropriate responding and response rate were
      assessed after intragastric administration of pentobarbital, the high efficacy
      benzodiazepines triazolam and clonazepam, and the low efficacy benzodiazepines
      imidazenil and bretazenil. Pentobarbital increased drug-appropriate responding to
      100% and decreased the response rate. Triazolam and clonazepam occasioned 80% or
      greater drug-appropriate responding in four out of four monkeys, and decreased
      response rate in three out of four monkeys. The antagonist flumazenil decreased
      drug-appropriate responding and increased response rate after triazolam and
      clonazepam, consistent with antagonism of the discriminative stimulus and the
      rate-altering effects of these ligands. Imidazenil occasioned 80% or greater drug
      appropriate responding in three out of four monkeys and suppressed the response
      rate in two out of four monkeys, whereas bretazenil occasioned 80% or greater
      drug-appropriate responding in two out of four monkeys and decreased the response
      rate slightly. Bretazenil, when co-administered with a dose of triazolam that
      produced 90-100% drug-appropriate responding, decreased responding to 0-60% but
      did not alter the rate-suppressing effects of this ligand. The rank order of
      potency (based on pmol/kg ED, values) was: triazolam > clonazepam > or =
      imidazenil > bretazenil. These results demonstrate differences in the
      pentobarbital-like discriminative stimulus and response rate-decreasing effects
      among benzodiazepine agonists. Specifically, full agonists engendered
      pentobarbital-like responding in all subjects with decreased response rates in
      most subjects, whereas partial agonists engendered pentobarbital-like responding
      and decreased response rates in subsets of subjects.

PMID- 10065929
TI  - The septum and the hippocampus differentially mediate anxiolytic effects of R(+)
      8-OH-DPAT.
AB  - Infusing the 5-HT1A receptor agonist R(+)-8-OH-DPAT into the septum or
      hippocampus reduced the fear responses of rats differentially in the elevated
      plus-maze and shock-probe burying tests, two rat models of anxiety. Intra-septal
      infusions of R(+)-8-OH-DPAT (5 and 10 microg) produced dramatic reductions in rat
      burying behavior in the shock-probe test, whereas it did not alter rat open-arm
      activity in the plus-maze test, across a wide range of doses (0.1, 0.25, 5 and 10
      microg). Conversely, intra-hippocampal infusions of R(+)-8-OH-DPAT (0.1 and 5
      microg/side) produced substantial increases in open-arm activity in the plus-maze
      test, but did not alter rat burying behavior in the shock-probe test. These
      dissociations suggest that 5-HT1A receptors in the septum and hippocampus exert
      parallel but distinct control over different fear reactions.

PMID- 10065930
TI  - Characterization of serotonergic mechanisms involved in the behavioural
      inhibition induced by 5-hydroxytryptophan in a modified light-dark test in mice.
AB  - In a modified light-dark exploration test in mice, 5-hydroxytryptophan, at doses
      (25-50 mg/kg) that approximately doubled the 5-HT content in the cerebral cortex,
      reduced the time spent by mice in the white compartment, suggesting an anxiogenic
      effect. Depletion of brain 5-HT content with p-chlorophenylalanine (300 mg/kg/day
      for three consecutive days) resulted in an anxiolytic-like effect. Conversely,
      the 5-HT reuptake blocker fluoxetine reduced the time spent by mice in the white
      compartment. No significant interaction of either p-chlorophenylalanine or
      fluoxetine with 5-hydroxytryptophan was found. Several 5-HT agents, some of them
      with an intrinsic anxiolytic-like effect in this test, were studied in
      combination with 5-hydroxytryptophan. All of the drugs with a selective affinity
      at 5-HT1A receptors interacted significantly with 5-hydroxytryptophan. The
      suppressant effect of 5-hydroxytryptophan was antagonized or reversed by
      buspirone, a partial agonist at postsynaptic 5-HT1A receptors, and also by the
      "silent" 5-HT1A receptor antagonist WAY 100635, but not by the full agonist 8-OH
      DPAT. The 5-HT2 receptor antagonist ritanserin partly counteracted the 5
      hydroxytryptophan effect at the lower dose used. The 5-HT3 receptor antagonist
      ondansetron was able to prevent, at a low dose, the anxiogenic effect of 5
      hydroxytryptophan; however, the 5-HT3 antagonists VA21B7 and granisetron as well
      as the 5-HT3/5-HT4 antagonist tropisetron and the selective 5-HT4 receptor
      antagonist RS 23597-190 were ineffective. The results appear to be consistent
      with the hypothesis that relates increased activity of the 5-HT systems to
      increased anxiety. Even though different 5-HT receptor subtypes may be involved
      in the anxiogenic effect of a high dose of 5-hydroxytryptophan, postsynaptic 5
      HT1A receptors appear to play a prominent role. Administration of 5
      hydroxytryptophan may consequently represent a valid approach to analyse further
      the role of 5-HT agents, in particular those acting at 5-HT1A receptors, in
      animal models of anxiety.

PMID- 10065931
TI  - The effects of convulsant and anticonvulsant treatments on the behavioural
      effects of ultrasound presentation in Lister hooded rats.
AB  - Lister hooded rats exhibit bursts of locomotion when exposed to a 20 kHz acoustic
      stimulus; this ultrasound-induced locomotion has been suggested as a potential
      model for panic attacks. The present studies determined the effects of treatment
      with the convulsant agents strychnine and pentylenetetrazole and the
      anticonvulsant agents pentobarbital and ethosuximide on locomotor behaviour
      elicited by experimenter-presented ultrasounds in Lister hooded rats. Behaviour
      in a circular arena was viewed live and tracked electronically. In Experiment 1,
      brief exposure to an ultrasound stimulus typically resulted in short intensity
      related bursts of locomotion in control rats. Pentobarbital or ethosuximide
      treatment reduced this short-term ultrasound-induced locomotion in a dose-related
      manner, whereas pentylenetetrazole or strychnine treatment increased these
      locomotor bursts. In Experiment 2, exposure to the ultrasound stimulus for a
      longer period resulted in irregular cycles of bursts of locomotion followed by
      periods of relative inactivity in control rats. In addition, approximately 10% of
      control rats exhibited convulsions associated with this long-duration ultrasound
      exposure at 98 dB sound pressure level. Sub-convulsant doses of the convulsant
      treatments increased the frequency of occurrence of convulsions associated with
      the ultrasound stimulus; pentobarbital or ethosuximide pretreatment significantly
      reduced this effect. The present findings suggest that a relationship exists
      between ultrasound-induced locomotor bursts and convulsant activity.

PMID- 10065932
TI  - Effects of d-amphetamine, diazepam and buspirone on schedule-induced polydipsia
      suppressed by response-dependent and response-independent shock.
AB  - Food deprived Wistar rats were exposed to a fixed time 60 s food schedule until
      they developed schedule-induced polydipsia. Rats were matched in pairs according
      to their licking rate, being designated experimental or yoked control at random.
      Every fifth lick by experimental rats was then followed by an electric shock
      (0.05, 0.1, or 0.2 mA) while the food schedule continued in operation. Yoked
      control rats received the same shocks as experimental rats, but independently of
      their own licking. Drugs were then tested on the suppressed rates of licking.
      Diazepam (0.5-2.0 mg/kg) increased punished schedule-induced polydipsia, a result
      not observed in yoked controls. No increases in the licks per minute of
      experimental or control animals were found after d-amphetamine (0.25-4.0 mg/kg)
      or buspirone (0.5-8.0 mg/kg). In comparison with previous results it is concluded
      that the antipunishment effects of drugs on schedule-induced behaviour depend on
      the type of punishment contingency.

PMID- 10065933
TI  - Behavioral and neurochemical components of nicotine sensitization following 15
      day pretreatment: studies on contextual conditioning.
AB  - The effects of contextual conditioning on the induction of nicotine sensitization
      of locomotor activity, stereotypy and nucleus accumbens dopamine release were
      studied using a 15-day pretreatment regimen. Six groups of Sprague-Dawley rats
      were employed to test for the effects of drug pretreatment, conditioning and
      novelty. Groups 1-4 were treated with daily nicotine (0.6 mg/kg, s.c.) or saline
      injections that were either paired with the test chamber or given in the home
      cage, followed by saline injections in the home cage. Group 5 received saline in
      the test chamber followed by nicotine in the home cage (unpaired). Group 6 was
      naive to handling and drug treatment. Pretreated animals were implanted with 2 mm
      microdialysis probes, via chronic guide cannulae, after completing the 15th day
      of treatment, and were tested for their response to nicotine (0.6 mg/kg, s.c) or
      saline on day 16. Naive animals were implanted with microdialysis probes and
      tested in a similar manner. Nicotine-stimulated locomotor activity was sensitized
      in the paired, unpaired and homecage pretreatment groups whereas nicotine
      stimulated stereotypy was sensitized only in the paired pretreatment group.
      Nicotine-stimulated nucleus accumbens dopamine release was sensitized in the
      paired and unpaired pretreatment groups. Saline-stimulated nucleus accumbens
      dopamine release, but not locomotor activity or stereotypy, was also found in the
      nicotine-pretreated, paired group. These findings demonstrate the development of
      sensitization to nicotine-induced locomotor activity, stereotypy and nucleus
      accumbens dopamine release after a 15-day pretreatment regimen. Each of these
      responses to nicotine were differentially modulated by contextual conditioning.
      It is suggested that nicotine-stimulated dopamine release in sensitized animals
      represents the conditioned component of nicotine sensitization.

PMID- 10065934
TI  - Effects of repeated withdrawal from chronic ethanol on oral self-administration
      of ethanol on a progressive ratio schedule.
AB  - Male hooded Lister rats were trained using a sucrose-fading technique, to perform
      an operant lever press response to obtain ethanol. Initial training, using an FR4
      schedule in which each reinforcement required four lever presses, included
      varying the concentration of ethanol in the liquid reinforcer. Changes in
      reinforcer concentration between 7 and 15% (vol/vol) had little effect on either
      numbers of lever pressing responses, or reinforcers obtained during the 3h
      session. Increasing the reinforcer concentration to 20% caused a decline in
      responding. The effects of varying reinforcer concentration (0-20% ethanol) were
      also studied in the same animals performing a progressive ratio schedule, in
      which the number of responses required to obtain a reinforcer was successively
      increased during the session. In these experiments the point at which rats ceased
      to respond (breaking point) was taken as a measure of their motivation to obtain
      ethanol. The function describing the relationship between ethanol concentration
      and number of responses, and number of reinforcers obtained in a session was an
      inverted U, with the maximum values occurring at an ethanol concentration of 10%.
      The value of the breaking point (highest ratio achieved) depended on the
      criterion used to define cessation of responding, but was between 15 and 22. Rats
      performing for ethanol showed higher breaking points than when responding for
      water, but there was no statistically reliable effect of ethanol concentration on
      the breaking point parameter. The effects of feeding the rats a liquid diet
      containing ethanol, and its subsequent withdrawal, on progressive ratio
      responding for 5% ethanol, were studied over four cycles of exposure and
      withdrawal. Intakes of ethanol of 11 g/kg/day had no effect on the animals'
      breaking point on the progressive ratio schedule, but withdrawal from the ethanol
      diet resulted in breaking points significantly higher than those in a control
      group pair-fed a nutritionally equivalent, ethanol-free diet. Although there was
      no further effect of repeated exposure and withdrawal on responding during the
      acute withdrawal phase, baseline levels of responding were elevated in the
      animals which had received multiple cycles of ethanol diet and withdrawal. These
      results are discussed in the context of the consequences of sensitization to
      repeated withdrawal from ethanol in dependent animals and humans.

PMID- 10065935
TI  - Interaction between midazolam-induced anterograde amnesia and memory enhancement
      by treatments given hours later in hippocampus, entorrhinal cortex or posterior
      parietal cortex.
AB  - Rats were bilaterally implanted with indwelling cannulae in the CA1 region of the
      dorsal hippocampus, the entorrhinal cortex or the posterior parietal cortex.
      After recovery from surgery, they were trained in a one-trial step-down
      inhibitory avoidance task using a 0.3 mA footshock. The animals received i.p. 15
      min before training either saline (1 ml/kg) or midazolam (1 mg/kg). Three hours
      after training they received, through the cannulae, infusions of saline,
      norepinephrine (0.3 microg/side), SKF38393 (7.5 microg/side), or 8-Br-cAMP (1.25
      microg/side) into the brain regions mentioned. Animals were tested for retention
      24 h after the training session. Midazolam produced anterograde amnesia, and the
      post-training treatments (with the exception of SKF38393 given into the
      entorrhinal cortex) caused retrograde memory facilitation. The amnestic effect of
      midazolam and the facilitatory effect of the treatments given into the brain
      cancelled each other out. Therefore, the mechanisms triggered by midazolam can
      interact with others in areas involved in memory processing several hours after
      their onset.

PMID- 10065936
TI  - Effects of delta-9-tetrahydrocannabinol and (R)-methanandamide on open-field
      behavior in rats.
AB  - This study compared the effects of (R)-methanandamide, an analog of the mammalian
      brain constituent anandamide, and delta-9-tetrahydrocannabinol on the open-field
      behavior of male Sprague-Dawley rats. Rats were individually housed with free
      access to food and water. Animals were treated with 0, 1, 3, and 5.6 mg/kg delta
      9-tetrahydrocannabinol given i.p. 30 min pre-session; and 0, 3, 10, and 18 mg/kg
      (R)-methanandamide, 15 min pre-session. The behavioral categories recorded were
      ambulation (the number of squares crossed), rearing (the number of times the rat
      stood erect on its hind-legs), latency (the time in seconds to leave the starting
      area, the circle in the center of the field), circling (the number of times the
      animal turned around its vertical axis, 0.5 point given for each 180 degrees
      turn), grooming (the number of cleaning bouts), urination and defecation (the
      number of urination spots and fecal boli deposited during the 5 min observation
      period). Delta-9-tetrahydrocannabinol was more potent than (R)-methanandamide,
      but otherwise the effects of delta-9-tetrahydrocannabinol and (R)-methanandamide
      were similar, with one exception; whereas delta-9-tetrahydrocannabinol produced
      dose-related increases in circling, (R)-methanandamide did not increase circling
      over the doses examined. The delta-9-tetrahydrocannabinol-induced increase in
      circling was blocked by the central cannabinoid receptor CB1 antagonist SR
      141716. The differential effects with regard to circling may indicate that there
      are qualitative behavioral differences in the effects of delta-9
      tetrahydrocannabinol and (R)-methanandamide.

PMID- 10065937
TI  - Latent inhibition of fear potentiated startle in rats.
AB  - Non-reinforced pre-exposure to a prospective conditioned stimulus impairs
      subsequent conditioning. This phenomenon is termed latent inhibition. In this
      report, we demonstrate latent inhibition in a classical conditioning procedure,
      the fear-potentiated startle reflex. Normally, the startle response is enhanced
      in the presence of a conditioned stimulus that has previously been paired with an
      aversive stimulus. We show that fear-potentiation of the startle response is
      significantly less pronounced in rats that have been repeatedly pre-exposed to a
      conditioned light stimulus. Similar to other procedures reported in the
      literature, the administration of the psychostimulant drug amphetamine (1.0
      mg/kg) before pre-exposure and conditioning disrupts latent inhibition. A good
      deal is known about the neuronal mechanisms underlying the acquisition and
      expression of fear-potentiated startle, and therefore this new procedure could be
      a useful tool for investigating the neuronal basis of latent inhibition.

PMID- 10065938
TI  - SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food
      intake in marmoset.
AB  - SR 141716 (1 and 3 mg/kg p.o.), a selective central (CB1) cannabinoid receptor
      antagonist, selectively reduced feeding of a very highly palatable cane-sugar
      mixture in marmosets. In contrast, standard primate pellet intake was not
      modified at the lower dose, but was slightly increased (+29%;p < 0.01) by the
      higher dose of SR 141716. These results are in agreement with the hypothesis that
      endogenous cannabinoid systems are involved in the modulation of the appetitive
      value of food.

PMID- 10065939
TI  - Evidence-based presentations: science or sham?

PMID- 10065940
TI  - Digital subtraction radiography: then (1983) and now (1998).

PMID- 10065941
TI  - Expression of collagen alpha1(I) mRNA variants during tooth and bone formation in
      the rat.
AB  - Collagen alpha1(I) mRNA is composed of two variants of 5 and 6 kb, differing in
      the length of the 3' untranslated region. In this work, the nucleotide sequences
      of the two rat mRNA variants were compared, and their expression pattern in cells
      forming bone, dentin, and cementum were analyzed. The sequences were determined
      from cDNA inserts of tooth and bone libraries plus directly from PCR fragments,
      obtained from bone. A total of 5721 bases of the rat collagen alpha1(I) sequence
      from cDNA of tooth and bone was determined. All sequences of the short variant
      were represented in the long variant. Only the alternatively poly-A additions
      gave rise to the variants in hard tissue. Two oligonucleotides were chosen as
      probes, one of which recognized, on Northern blots, the two bands of 5 and 6 kb,
      and the other the 6-kb variant only. The oligonucleotides were used in in situ
      hybridization experiments, for study of the distribution of the variants in
      different extracellular matrix-forming cells. Osteoblasts, odontoblasts, and
      cementum-associated cells were closely examined in sections from rat maxillae
      from 2 to 25 days of age. A similar or identical pattern of mRNA expression was
      observed with both oligonucleotides, indicating that the two mRNA variants were
      co-expressed in all cases.

PMID- 10065942
TI  - Aberrant gene expression in epithelial cells of mixed odontogenic tumors.
AB  - Comparative investigations of odontogenic cells in normally forming teeth and
      tumors may provide insights into the mechanisms of the differentiation process.
      The present study is devoted to late phenotypic markers of ameloblast and
      odontoblast cells, i.e., proteins involved in biomineralization. The in situ
      expression of amelogenins, keratins, collagens type III and IV, vimentin,
      fibronectin, osteonectin, and osteocalcin was performed on normal and tumor
      odontogenic human cells. The pattern of protein expression showed some
      similarities between ameloblasts and odontoblasts present in normally developing
      human teeth and cells present in neoplastic tissues of ameloblastic fibroma,
      ameloblastic fibro-odontomas, and complex odontomas. Amelogenins (for
      ameloblasts) and osteocalcin (for odontoblasts) were detected in cells with well
      organized enamel and dentin, respectively. In contrast, "mixed" cells located in
      epithelial zones of mixed odontogenic tumors co-expressed amelogenins and
      osteocalcin, as shown by immunostaining. The presence of osteocalcin transcripts
      was also demonstrated by in situ hybridization in these cells. Keratins and
      vimentin were detected in the same epithelial zones. Tumor epithelial cells were
      associated with various amounts of polymorphic matrix (amelogenin- and
      osteocalcin-immunoreactive), depending on the types of mixed tumors. No
      osteocalcin labeling was found in epithelial tumors. This study confirms that the
      differentiation of normal and tumor odontogenic cells is accompanied by the
      expression of some common molecules. Furthermore, the gene products present in
      normal mesenchymal cells were also shown in odontogenic tumor epithelium. These
      data may be related to a tumor-specific overexpression of the corresponding genes
      transcribed at an undetectable level during normal development and/or to an
      epithelial-mesenchymal transition proposed to occur during normal root formation.
      A plausible explanation for the results is that the odontogenic tumor epithelial
      cells are recapitulating genetic programs expressed during normal odontogenesis,
      but the tumor cells demonstrate abnormal expression patterns for these genes.

PMID- 10065943
TI  - Contribution of jaw muscle size and craniofacial morphology to human bite force
      magnitude.
AB  - The existence of an interaction among bite force magnitude, jaw muscle size
      (e.g., cross-sectional area, thickness), and craniofacial morphology is widely
      accepted. Bite force magnitude depends on the size of the jaw muscles and the
      lever arm lengths of bite force and muscle forces, which in turn are dictated by
      craniofacial morphology. In this study, the relative contributions of
      craniofacial morphology and jaw muscle thickness to the bite force magnitude were
      studied. In 121 adult individuals, both magnitude and direction of the maximal
      voluntary bite force were registered. Craniofacial dimensions were measured by
      anthropometrics and from lateral radiographs. The thicknesses of the masseter,
      temporal, and digastric muscles were registered by ultrasonography. After a
      factor analysis was applied to the anthropometric and cephalometric dimensions,
      the correlation between bite force magnitude, on the one hand, and the
      "craniofacial factors" and jaw muscle thicknesses, on the other, was assessed by
      stepwise multiple regression. Fifty-eight percent of the bite force variance
      could be explained. From the jaw muscles, only the thickness of the masseter
      muscle correlated significantly with bite force magnitude. Bite force magnitude
      also correlated significantly positively with vertical and transverse facial
      dimensions and the inclination of the midface, and significantly negatively with
      mandibular inclination and occlusal plane inclination. The contribution of the
      masseter muscle to the variation in bite force magnitude was higher than that of
      the craniofacial factors.

PMID- 10065944
TI  - The theoretical optimal center of rotation for a temporomandibular joint
      prosthesis: a three-dimensional kinematic study.
AB  - A unilateral temporomandibular joint (TMJ) prosthesis may cause dysfunction of
      the contralateral, natural TMJ because of lack of translatorial movements of the
      prosthetic side. The natural translatorial capacity of the mandible can be
      restored in part by a TMJ prosthesis with a fixed center of rotation (CR),
      positioned inferiorly to the center of the natural mandibular condyle. The aim of
      this study was to determine the optimal position for the fixed CR of a unilateral
      TMJ prosthesis. A mathematical model was used to analyze different positions of
      the CR. These positions were evaluated based on the calculated rotation of the
      mandible in the frontal (theta f) and horizontal (theta h) plane, and the
      mediolateral movement (MLM) of the contralateral natural condyle. For current TMJ
      prostheses, with the CR positioned in the center of the natural condyle, theta h
      exceeded the natural limits. When the CR was shifted inferiorly, all parameters
      improved, particularly theta h. The addition of an anterior shift to an inferior
      shift slightly worsened theta f, while the addition of a posterior shift to an
      inferior shift slightly improved theta f and worsened MLM. We concluded that the
      functioning of the contralateral TMJ improves by shifting the CR inferiorly. An
      anterior shift may be added to remain within the contour of the mandibular ramus.
      The proposed position of the CR is 15 mm inferior to the center of the natural
      condyle, combined, if necessary, with an additional anterior shift of 5 mm.

PMID- 10065945
TI  - Origin of primary sensory neurons innervating the buccal stretch receptor.
AB  - The primary sensory neurons innervating mechanoreceptors in oro-facial regions
      have their cell bodies in either the trigeminal ganglion or the mesencephalic
      nucleus of the trigeminal nerve. The buccal stretch receptor (BSR), a type of
      mechanoreceptor in the jaw of rodents, has recently been recognized as signaling
      the position of the mandible. The location of the primary afferent neurons
      innervating this receptor is unknown. To investigate the cell bodies of the BSR
      afferent neurons in rats, we applied wheat germ agglutinin-horseradish peroxidase
      (WGA-HRP) to the proximal stump of the severed nerve branch of the buccal nerve
      that supplied the BSR. HRP-labeled cell bodies were observed in the
      posterolateral portion of the ipsilateral trigeminal ganglion. None was found in
      the contralateral trigeminal ganglion or in the brainstem. All labeled cell
      bodies were oval or round and closely resembled pseudo-unipolar neurons. The mean
      diameter of the labeled somata ranged between 25.5 and 52.5 microm, with small (<
      or = 30 microm), medium (from 31 to 40 microm), and large somata (> or = 41
      microm) accounting for 8.8%, 54.9%, and 36.3%, respectively. Among the myelinated
      nerve fibers in the branch in which WGA-HRP was applied, 78.5% terminated in the
      BSR and had larger fiber diameters than the rest, indicating that most of the
      medium and large HRP-labeled cell bodies were BSR afferents. From these results
      and the ontogenetic origin of this receptor, it is suggested that the BSR
      differentiated from the mechanoreceptors in the oral mucosa or the fascia of
      masticatory muscles.

PMID- 10065946
TI  - Activation of excitatory amino acid receptors in bovine dental pulp evokes the
      release of iCGRP.
AB  - The activation of excitatory amino acid (EAA) receptors within the central
      nervous system is associated with numerous centrally mediated phenomena,
      including hyperalgesia. However, relatively little is known about the peripheral
      mechanisms which these receptors may regulate when activated. This research
      evaluated the hypothesis that EAA receptors in bovine dental pulp activate a
      population of peptidergic sensory neurons as measured by the release of
      immunoreactive calcitonin gene-related peptide (iCGRP), a neuropeptide associated
      with neurogenic inflammation. In vitro superfusion of bovine dental pulp was used
      to evaluate the regulation of iCGRP secretion by the EAA receptor agonists AMPA,
      kainate, NMDA, and L-glutamate. Both AMPA and kainate stimulated the release of
      iCGRP in a concentration-dependent manner (AMPA EC50 = 0.27 +/- 3.3 nM; kainate
      EC50 = 3.2 +/- 1.1 microM). Pre-treatment and co-administration of the
      AMPA/kainate receptor antagonist CNQX significantly reduced the iCGRP release
      evoked by either of these agonists. In contrast, neither NMDA nor L-glutamate
      induced any consistent changes in iCGRP release. These results suggest that the
      activation of AMPA and kainate receptors in dental pulp may contribute to
      peripheral release of vasoactive neuropeptides which mediate a neurogenic
      component of inflammation.

PMID- 10065947
TI  - Signal transduction pathways involved in the synergistic stimulation of
      prostaglandin production by interleukin-1beta and tumor necrosis factor alpha in
      human gingival fibroblasts.
AB  - Accumulating evidence indicates that prostaglandins play an important role in the
      pathogenesis of periodontal disease. In this study, the effects and interactions
      between IL-1beta and TNFalpha on prostaglandin production and its regulation were
      investigated. The cytokines IL-1beta and TNFalpha stimulated prostaglandin E2
      (PGE2) and prostacyclin (PGI2) production in gingival fibroblasts. Simultaneous
      treatment of the cells with IL-1beta and TNFalpha resulted in a synergistic
      stimulation of PGE2 and PGI2 formation. IL-1beta and, to a lesser extent,
      TNFalpha stimulated the release of 3H-arachidonic acid (3H-AA), and simultaneous
      addition of IL-1beta and TNFalpha further increased the release of 3H-AA from pre
      labeled gingival fibroblasts. Furthermore, IL-1beta and, to a lesser extent,
      TNFalpha induced the expression of cyclooxygenase-2 (COX-2) mRNA. Simultaneous
      addition of IL-1beta and TNFalpha synergistically enhanced COX-2 mRNA levels,
      accompanied by a corresponding stimulation of PGE2 synthesis. Neither IL-1beta,
      TNFalpha, nor the combination of these two cytokines affected COX-1 mRNA levels.
      PMA, known to activate protein kinase C (PKC), enhanced the stimulatory effect of
      IL-1beta, TNFalpha, and the combination on COX-2 mRNA levels accompanied by a
      corresponding increase in PGE2 production. The phospholipase A2 (PLA2) inhibitor,
      BPB, and the PKC inhibitor, BIS, reduced PGE2 production, whereas dexamethasone,
      indomethacin, and NS-398 completely abolished PGE2 production induced by IL
      1beta, TNFalpha, and the combination. The study indicates that the synergistic
      stimulation of prostaglandin production by IL-1beta, and TNFalpha is mediated
      partly at the level of COX-2 and partly at the level of PLA2 and that PKC is
      involved in the signal transduction of the synergy between the two cytokines. The
      synergy between IL-1beta and TNFalpha may play an important role in the
      inflammatory processes in gingival tissue in vivo.

PMID- 10065948
TI  - Direct interaction between gingival fibroblasts and lymphoid cells induces
      inflammatory cytokine mRNA expression in gingival fibroblasts.
AB  - In inflamed periodontal lesions, dense infiltration of lymphocytes is usually
      observed in the extravascular periodontal connective tissue, adjacent to gingival
      fibroblasts. Our previous study revealed that activated lymphocytes can
      adhesively interact with gingival fibroblasts in vitro. In the present study, we
      investigated whether gingival fibroblasts are activated through direct
      interaction with lymphoid cells by monitoring the expression of inflammatory
      cytokine mRNA in human gingival fibroblasts (HGF). Co-culture with various human
      lymphoid cells in vitro resulted in a marked increase in the expression of IL
      1alpha, IL-1beta, and IL-6 mRNA by the HGF. In addition, expression of the mRNA
      of the IL-1beta-converting enzyme (ICE), which is essential to produce the mature
      form of IL-1beta, was constitutively observed in the HGF, suggesting that mature
      IL-1beta is produced by these cells. When HGF were cultured with the culture
      supernatant of the lymphoid cells, the increase in the inflammatory cytokine mRNA
      expression was not observed. Similarly, when HGF and lymphoid cells were cultured
      in the same well but separated by a membrane which prevented direct contact
      between the cells, no increase in inflammatory cytokine mRNA expression was
      observed. These results strongly indicate that direct interaction between these
      heterotypic cell types transduces activation signals into HGF that induce an
      increase in inflammatory cytokine mRNA expression. Furthermore, IL-1beta mRNA
      expression in the HGF was synergistically increased when HGF directly interacted
      with lymphoid cells in the presence of exogeneous IL-1beta. The present study
      demonstrates that direct interaction between HGF and lymphoid cells stimulates
      HGF to increase inflammatory cytokine mRNA expression, and raises the possibility
      that heterotypic cell-cell interaction may facilitate local inflammatory
      reactions.

PMID- 10065949
TI  - Dominant cross-reactive antibodies generated during the response to a variety of
      oral bacterial species detect phosphorylcholine.
AB  - The intraperitoneal immunization of Balb/c mice with subgingival plaque from
      advanced periodontal pockets or with certain strains of Actinobacillus
      actinomycetemcomitans, Fusobacterium nucleatum, Actinomyces israelii,
      Streptococcus mitis, or Streptococcus oralis yielded frequently indistinguishable
      IgM monoclonal antibodies which were reactive with antigens from a variety of
      oral bacteria. This study aimed to characterize the specificity of such
      monoclonal antibodies and the diversity of oral bacteria expressing this target
      antigen or epitope. Using a competitive enzyme-linked immunosorbent assay to
      study a variety of competitor substances for their capacity to bind to the
      monoclonal antibodies, we identified phosphorylcholine as the recognized epitope.
      The concentration of positive bacteria with extraordinarily bright cell wall
      fluorescence in indirect immunofluorescence assays varied between 0.1% and 15% in
      subgingival and from 10 to 40% in supragingival plaque samples. Labeled bacteria
      belonged to different morphotypes, including cocci, rods, and filaments. Of 75
      species tested in vitro, 14 gram-positive and four gram-negative species were
      found to harbor positive strains. Haemophilus aphrophilus, Streptococcus mitis,
      Actinomyces georgiae, Actinomyces gerencseriae, Actinomyces israelii, and
      Actinomyces odontolyticus were human oral species of which all tested strains
      were capable of binding the cross-reactive monoclonal antibodies. In contrast,
      Actinomyces naeslundii was consistently negative. These data provide evidence for
      a much more common expression of phosphorylcholine by oral bacteria than hitherto
      believed but do not indicate an obvious association of phosphorylcholine
      expression with oral health or inflammatory periodontal diseases.

PMID- 10065950
TI  - Ion distribution in matrix parts of glass-polyalkenoate cement by SIMS.
AB  - The microstructure of the set glass-polyalkenoate cement has not been undertaken
      beyond a study where an Electron Probe Micro Analyser was used. The purpose of
      this investigation was to determine the ion distribution in matrix parts of the
      set cement by means of Secondary Ion Mass Spectrometry (SIMS). Among the
      techniques for surface and microscopic analysis, SIMS is said to be the one with
      the highest sensitivity. O2+ ions were used as the beam probe to detect silicon,
      aluminum, calcium, sodium, and carbon. The scanning images showed a clear
      difference among these elements in their distribution. A large amount of aluminum
      was found throughout the matrix area, with only a slight concentration gradient,
      while silicon appeared to be concentrated on the surface of the undissolved glass
      core. The distribution pattern of calcium was not as clear as that shown by
      aluminum and silicon. A comparatively higher content of carbon was found closer
      to the glass surface. These results indicate that aluminum plays an essential
      role in the setting of the matrix and the surface of the glass dissolved by
      acrylic acid and changed into the siliceous gel.

PMID- 10065951
TI  - Gradient elution capillary electrochromatography and hyphenation with nuclear
      magnetic resonance.
AB  - Coupling of gradient capillary electrochromatography (gradient CEC) and capillary
      zone electrophoresis (CZE) with nuclear magnetic resonance spectroscopy (NMR) was
      performed using a recently developed capillary NMR interface. This technique was
      applied for the analysis of pharmaceuticals and food. An analgesic was
      investigated using isocratic and gradient continuous-flow CEC-NMR. Comparison of
      the results demonstrated the superiority of gradient CEC over isocratic CEC.
      Aspartame and caffeine, both ingredients of soft beverages, were separated and
      analyzed by continuous flow CZE-NMR. The order of elution could be reversed by
      altering the pH. This reversal led to an increased sample concentration in the
      NMR detection cell, thus allowing the acquisition of a totally correlated
      spectroscopy (TOCSY) two-dimensional (2-D) spectrum of the synthetic peptide
      aspartame.

PMID- 10065952
TI  - Voltage-induced variation of distribution coefficient in electrochromatography.
AB  - Upon application of an electric field along a column packed with anion exchange
      support materials, the output of a recorder jumps beyond the baseline, and with
      continued application a peak is obtained. If, instead, the electric field is
      applied in a pulsed manner, two peaks result. These observations are explained as
      caused by a change in the concentration of the solvent. Applying positive and
      negative voltages produces positive and negative peaks, respectively. The peak
      height depends on the value of applied voltage. Simulations using the plate
      height theory agree well with chromatograms obtained experimentally. The value of
      the local applied voltage is also estimated. Overall, the behavior is something
      like an injection arising from the pulsed application of an electric field. We
      suggest that voltage pulsing might be used as a new technique for sample
      injection.

PMID- 10065953
TI  - Capillary electrochromatography with segmented capillaries for controlling
      electroosmotic flow.
AB  - Capillaries consisting of two segments each packed with a different stationary
      phase were introduced for the control and manipulation of the electroosmotic flow
      (EOF) in capillary electrochromatography (CEC). This kind of column configuration
      was called segmented capillary where one segment was packed with octadecyl silica
      (ODS) and served as the separation segment while the other segment was packed
      with bare silica and functioned as the EOF accelerator segment. The average flow
      in the segmented capillary increased linearly with increasing fractional length
      of the EOF accelerator segment, and consequently the analysis time was reduced.
      Under a given set of conditions, the average flow can be varied over a certain
      range that extends from the EOF in the individual ODS capillary at the lower end
      to the EOF in the individual bare silica capillary at the higher end. The pore
      size of the bare silica in the EOF accelerator segment influenced the average
      flow in the segmented capillary. Because of the difference in the EOF of the
      individual segments, the average flow across the segmented capillary is partially
      degenerated from EOF to viscous flow. Furthermore, the retaining frits in CEC
      columns are restrictive points which slow down the average flow, thus furthering
      the degeneration of the flow from EOF to viscous flow. In other words, in CEC
      columns containing retaining frits, the flow of the mobile phase is not only
      based on electroosmosis but is contaminated by a viscous component.

PMID- 10065954
TI  - Preparation of capillary columns coated with linear polymer containing
      hydrophobic and charged groups for capillary electrochromatography.
AB  - A linear polymer-coated capillary was prepared by in-capillary copolymerization
      of N-tert-butylacrylamide (TBAAm) with a charged monomer, 2-acrylamido-2-methyl-1
      propanesulfonic acid (AMPS), after the capillary pretreatment with a bifunctional
      reagent. The coated capillaries were applied in capillary electrochromatographic
      (CEC) separation of small neutral compounds. Hydrophobic groups in the linear
      polymer, which were immobilized onto the capillary surface, functioned as the
      stationary phase in reversed-phase CEC separation, and charged groups in the
      linear polymer generated electroosmotic flow (EOF) along the column. The coated
      capillaries were prepared by a simple procedure. Moreover, the reproducibility
      with respect to EOF rate and migration times of the solutes was excellent. The
      results for CEC separation of small molecules using the linear polymer-coated
      capillaries are presented.

PMID- 10065955
TI  - Capillary electrochromatography with novel stationary phases: II. Studies of the
      retention behavior of nucleosides and bases on capillaries packed with octadecyl
      sulfonated-silica microparticles.
AB  - An octadecyl-sulfonated silica (ODSS) stationary phase specially designed for
      performing capillary electrochromatography (CEC) at relatively strong
      electroosmotic flow (EOF) proved useful for the separations of some nucleosides
      and bases. The ODSS stationary phase is composed of a hydrophilic, negatively
      charged sublayer to which a nonpolar top layer containing octadecyl ligands is
      covalently attached. The charged sublayer contains sulfonic acid groups which
      ensure a relatively strong EOF. Due to the presence of permanently charged
      sulfonic acid groups in the sublayer, the hydrophilic nature of the sublayer and
      the hydrophobic character of the top octadecyl layer, retention and selectivity
      of charged and relatively polar nucleosides and bases on the ODSS stationary
      phase are based on electrostatic interaction, hydrophilic interaction, and
      reversed-phase mechanisms. This yielded for the ODSS stationary phase a unique
      selectivity towards the nucleosides and bases, thus allowing their rapid
      separation. To gain insight into the chromatographic behavior of nucleosides and
      bases on the ODSS stationary phase, the results were compared to those obtained
      on an octadecyl-silica (ODS) capillary under otherwise the same elution
      conditions. Due to the difference in the nature of the organic layers on the
      surface of the ODSS and ODS stationary phases, the elution order on both
      stationary phases differed significantly, and the ODSS capillary proved more
      suitable for the separation of the nucleosides and bases than the ODS capillary.

PMID- 10065956
TI  - Capillary electrochromatography using a fluoropolymer as the chromatographic
      support material.
AB  - Fused-silica capillary columns were packed with ethylene chlorotrifluoroethylene
      (ECTFE) particles for use in capillary electrochromatography (CEC).
      Electroosmotic flow (EOF) was generated in these columns using acetonitrile-water
      mixtures as the mobile phase. Electroosmotic mobilities of 1.6 x 10(-4) cm2 V(-1)
      s(-1) (linear velocities of 1 mm s(-1)) were observed using a mobile phase
      without an electrolyte present. The EOF in the ECTFE-packed columns is enhanced
      when using trifluoroacetic acid (TFA) as a mobile phase additive; electroosmotic
      mobilities of 3.65 x 10(-4) cm2 (V-1) s(-1) (linear velocity of 2.5 mm s(-1))
      were observed. This enhancement of EOF is attributed to dynamic coating of the
      ECTFE particles by TFA. Other electrolytes (i.e., Tris/Tris-HCl buffer and H3PO4)
      in the mobile phase did not have such an enhancement of EOF. However, a slight
      enhancement of EOF is observed, for example, if small quantities of TFA are added
      to the mobile phase containing Tris buffer. The potential of ECTFE for CEC is
      demonstrated by separating a mixture of amino acids.

PMID- 10065957
TI  - Fritless capillary electrochromatography.
AB  - The preparation of packed capillaries with stable frits of good quality can be a
      hurdle to obtain efficient separations in capillary electrochromatography (CEC).
      Especially with particles smaller than 3 microm, frit preparation is cumbersome.
      Highly efficient separations using packed capillaries without frits are
      presented. Under appropriate CEC conditions the particles were retained by
      electrophoretic attraction towards the anode by a tapered capillary inlet,
      without the need of a frit at the outlet end. Such fritless capillaries, packed
      with 1.5 microm nonporous reversed-phase particles, allowed separations with
      efficiencies of more than 500,000 plates/m. Once the capillaries were conditioned
      properly, more than 100 separations could be performed with good repeatability.
      With respect to separation efficiency, fritless capillaries packed with 3 microm
      particles were comparable with standard CEC capillaries with frits. Examples of
      separations of steroids, a pesticide and its by-products, and cardiac glycosides
      under various CEC conditions are shown.

PMID- 10065958
TI  - Silicate entrapped columns--new columns designed for capillary
      electrochromatography.
AB  - Designed especially for capillary electrochromatography (CEC), silicate-entrapped
      columns are made by trapping particles of chromatographic packing material in a
      network of silica. Once entrapped, the capillary no longer requires frits. This
      renders a more homogeneous and stable packed bed. Accidental breakage of the
      fragile frits is not an issue with these robust columns. Columns packed with
      reverse-phase material subjected to silicate entrapment demonstrated faster
      separations of retained analytes and increased efficiencies compared with
      nonentrapped columns. The method was also used to prepare chiral CEC columns by
      entrapping a molecular imprinted polymeric (MIP) packing having minimal surface
      charge density, thus being unable alone to support sufficient electroosmotic flow
      for CEC.

PMID- 10065959
TI  - Selective trace enrichment by immunoaffinity capillary electrochromatography on
      line with capillary zone electrophoresis - laser-induced fluorescence.
AB  - Limited by the lack of a sensitive, universal detector, many capillary-based
      liquid-phase separation techniques might benefit from techniques that overcome
      modest concentration sensitivity by preconcentrating large injection volumes. The
      work presented employs selective solid-phase extraction by immunoaffinity
      capillary electrochromatography (IACEC) to enhance detection limits. A model
      analyte, fluorescein isothiocyanate (FITC) biotin, is electrokinetically applied
      to a capillary column packed with an immobilized anti-biotin-IgG support. After
      selective extraction by the immunoaffinity capillary, the bound analyte is
      eluted, migrates by capillary zone electrophoresis (CZE), and is detected by
      laser-induced fluorescence. The column is regenerated and reused many times. We
      evaluate the performance of IACEC for selective trace enrichment of analytes
      prior to CZE. The calibration curve for FITC-biotin bound versus application time
      is linear from 10 to 300 seconds. Recovery of FITC-biotin spiked into a diluted
      urinary metabolites solution was 89.4% versus spiked buffer, with a precision of
      1.8% relative standard deviation (RSD).

PMID- 10065960
TI  - Design and evaluation of a new capillary electrochromatography system.
AB  - A new computer-controlled capillary electrochromatography (CEC) system was built.
      Up to +/- 60 kV can be used for CEC separation, and buffer vials can be
      pressurized to prevent bubble formation and to facilitate conditioning and
      rinsing of columns. This CEC system is compact and flexible. Short columns can be
      used to achieve fast separations. A fiber optic detection assembly is used to
      separate the main body of the UV detector from the high potential to prevent
      potential discharge and disturbance of the UV absorbance signal. This system was
      evaluated by separating 16 polycyclic aromatic hydrocarbons (PAHs) on different
      types of octadecyl silane (ODS) particles. Over 200,000 plates/m (k = 4.4) were
      obtained using 1.5 microm ODS particles. Voltage programming was used to reduce
      the analysis time by nearly 50%.

PMID- 10065961
TI  - Analysis of free fatty acids and fatty acid phenacyl esters in vegetable oils and
      margarine by capillary electrochromatography.
AB  - Capillary electrochromatography (CEC) has been utilized to analyze free fatty
      acids (FFAs) and fatty acid phenacyl esters (FAPEs) originating from vegetable
      oils and margarine. The analyses were performed on capillaries 25 and 40 cm long,
      100 microm ID, and packed with 3 microm Hypersil ODS. Isocratic elution was
      achieved with the mobile phase acetonitrile/50 mM 2-(N-morpholino)ethane sulfonic
      acid (MES), pH 6, at a ratio of 9:1. For quantitative analysis, the formation of
      FAPE derivatives is preferred. Moreover, the number of double bonds in the FAPEs
      can be elucidated by measuring the UV absorbance ratio of 240:210 nm. For the
      determination of the oleate/elaidate ratio in margarines, the FFAs are analyzed
      because of overlap of elaidate/palmitate in FAPE analysis. Data obtained with CEC
      and micro liquid chromatography (LC) were compared and CEC was found to be far
      superior in terms of efficiency and speed of analysis. Important selectivity
      differences were noted between micro LC on highly endcapped ODS and CEC on the
      silanol-rich Hypersil ODS.

PMID- 10065962
TI  - Tryptic digest mapping by gradient capillary electrochromatography.
AB  - A high performance liquid chromatography (HPLC) system complemented with T-split,
      capillary detection cell and a high voltage power supply was used for peptide
      mapping by gradient electrochromatography and nanoliquid chromatography (nano
      LC). With capillary columns of 100 microm ID, 6 cm packed with octadecylated 1.5
      microm silica particles, the typical analysis time was approximately 10-15 min.
      The resolution of a tryptic digest of cytochrome c obtained by
      electrochromatography at 100 kV/m was superior compared to the analysis by nano
      LC. Bubble formation caused by Joule heating at currents up to 100 microA was
      successfully suppressed by using a resistor capillary of 25 microm ID connected
      to the outlet of the packed column.

PMID- 10065963
TI  - Nonaqueous media for separation of nonionic organic compounds by capillary
      electrophoresis.
AB  - For the separation of neutral compounds by micellar electrokinetic
      chromatography, separations are usually carried out in predominantly aqueous
      solution in order to preserve the charged micelle necessary for the separation.
      We now show that polycyclic aromatic hydrocarbon (PAH) compounds can be separated
      efficiently by capillary electrophoresis in pure methanol or in aqueous-organic
      mixtures containing a high percentage of methanol. Sodium tetradecyl sulfate was
      the preferred surfactant. The effects of pH, solvent composition, surfactant
      structure, and surfactant concentration on the separations were studied.
      Reproducible migration times and linear calibration plots were obtained.

PMID- 10065964
TI  - Discontinuous electrokinetic chromatography of parabens using different
      substituted resonances as pseudostationary phases.
AB  - Resorcarene derivatives, negatively charged even at moderate pH, were synthesized
      and employed as pseudostationary phases to achieve mobilities exceeding that of
      the electroosmotic flow. Under these conditions, a discontinuous electrolyte
      system was developed which allows the separation of four uncharged homologous 4
      hydroxybenzoic esters (parabens) within a zone of resorcarene electrolyte, and
      the detection of these UV active compounds in a resorcarene-free zone, free from
      the high UV background absorbance of the resorcarenes. Resorcarenes, with
      differently charged functionalities (carboxylate and phosphate groups) to provide
      the electrophoretic mobility and with alkyl residues of different chain lengths
      responsible for the chromatographic interactions with the analytes, were tested
      and compared in terms of mobility and selectivity. Only the resorcarene
      phosphates exhibited sufficient mobilities at low pH exceeding the mobility of
      the electroosmotic flow (EOF). Retention factors of the parabens were found to
      increase with increasing chain length of the alkyl residues attached to the
      resorcarene. However, maximum selectivity was observed for an intermediate chain
      length (C8). An equation for the calculation of retention factors in
      discontinuous electrokinetic chromatography (EKC) is presented.

PMID- 10065965
TI  - Adjusting selectivity in micellar electrokinetic capillary chromatography with
      1,2-hexanediol.
AB  - In this report, we introduce a new micelle modifier useful to alter selectivity
      in micellar electrokinetic capillary chromatography (MECC). 1,2-Hexanediol acts
      as a class I organic modifier in that its effects are on the sodium dodecyl
      sulfate (SDS) micellar rather than the surrounding aqueous phase. This
      characteristic allows 1,2-hexanediol to improve resolution when applied at
      concentrations as low as 20 mM (0.25% v/v) by altering the selectivity observed
      with SDS alone. The effects of 1,2-hexanediol on the critical micelle
      concentration of SDS, electroosmotic flow, electrophoretic mobility of the SDS
      micelle, and reproducibility are presented. 1,2-Hexanediol had little impact on
      the migration time window at concentrations below 100 mM. Changes in selectivity
      induced by 1,2-hexanediol for a large set of model compounds are presented.
      Analytes capable of forming hydrogen bonds tend to decrease their interactions
      with the micellar phase while nonhydrogen bonding analytes increase their
      interactions. The usefulness of 1,2-hexanediol was demonstrated by examining its
      effects on the separation of dansylated amino acids. Eighteen of twenty amino
      acids could be separated with a resolution greater than 1.6 within 1600 s using a
      combination of 1,2-hexanediol and isopropanol.

PMID- 10065966
TI  - Separation of linoleic acid oxidation products by micellar electrokinetic
      capillary chromatography and nonaqueous capillary electrophoresis.
AB  - In this work the suitability of micellar electrokinetic capillary chromatography
      (MEKC) and nonaqueous capillary electrophoresis (CE) to the analysis of the
      primary oxidation products of linoleic acid was studied with uncoated fused
      silica capillaries. The primary autoxidation products of linoleic acid are the
      four hydroperoxide isomers 13-hydroperoxy-cis-9, trans-11-octadecadienoic acid,
      13-hydroperoxy-trans-9, trans-11-octadecadienoic acid, 9-hydroperoxy-trans-10,cis
      12-octadecadienoic acid, 9-hydroperoxy-trans-10, trans-12-octadecadienoic acid.
      Addition of a surfactant such as sodium dodecyl sulfate (SDS) or sodium cholate
      (SC) into the running buffer (20-30 mM 3-(cyclohexylamino)-1-propanesulfonic acid
      (CAPS) or ammonium acetate, pH 9.5-11) was required to enhance the water
      solubility of the sample and selectivity of the separation. MEKC proved to be a
      promising new technique for the separation of the primary oxidation products of
      lipids giving results comparable to high performance liquid chromatography
      (HPLC). Partial separation of hydroperoxide isomers was also achieved using
      nonaqueous CE with methanol-acetonitrile-sodium cholate as running buffer.

PMID- 10065967
TI  - Microchannel electrophoretic separation of biogenic amines by micellar
      electrokinetic chromatography.
AB  - Fast, efficient separation of most common biogenic amines was successfully
      performed on a glass microchip capillary electrophoresis device. The amines
      putrescine, histamine, tyramine, cadaverine, phenethylamine, tryptamine,
      spermidine and spermine were derivatized prior to fluorescence detection with
      fluorescein isothiocyanate. Separation was carried out using a channel length of
      28 mm, a cross section of 50 x 8 microm, and a field strength of 600 V/cm. After
      optimization of buffer electrolyte conditions (120 mM boric acid, pH 9.4,
      modified with 40 mM SDS), fluorescein thiocarbamyl amine derivatives were
      successfully resolved. Analysis time was as short as 75 s. Determination of the
      biogenic amines was achieved in soy sauce samples.

PMID- 10065968
TI  - Micellar electrokinetic capillary chromatography for the separation of cefalexin
      and its related substances.
AB  - Micellar electrokinetic capillary chromatography (MEKC) was examined for analysis
      of cefalexin and its related substances. Good selectivity was obtained with two
      different buffer solutions: a sodium acetate buffer (50 mM, pH 5.25) containing
      sodium dodecyl sulfate (50 mM SDS) or sodium phosphate buffer (40 mM, pH 7.0)
      containing 100 mM SDS. Both methods permit cefalexin to be completely separated
      from its ten related substances within 20 min. The robustness of the method,
      using pH 5.25 acetate buffer, was examined by means of a full-fraction factorial
      design to test the influence of buffer pH, concentration of SDS and buffer
      concentration. The parameters for validation such as linearity, precision, limit
      of detection and limit of quantitation are also reported. The results show that
      method 1 is suitable for the analysis of cefalexin.

PMID- 10065969
TI  - Highly efficient separation of isomeric epoxy fatty acids by micellar
      electrokinetic chromatography.
AB  - A capillary electrophoresis (CE) method has been developed for simple and direct
      separation of cis- and trans-12,13-epoxy-9(Z)-octadecenoic acid and 9,10-epoxy
      12(Z)-octadecenoic acid isomers. Separation was performed in micellar
      electrokinetic capillary chromatography (MEKC) using a buffer consisting of 25 mM
      borate (pH 9.20), 10 mM sodium dodecyl sulfate (SDS) and 10% v/v acetonitrile.
      The key variables, concentrations of SDS and organic modifier, were optimized by
      the application of a factorial experimental design. The use of a low micellar
      concentration, just above critical micelle concentration (CMC), in a background
      electrolyte containing an organic modifier not only made it possible to dissolve
      and separate highly hydrophobic fatty acid isomers, but also resulted in improved
      separation efficiency and selectivity. Separation efficiency up to 4 x 10(5)
      theoretical plates/m was achieved under an optimized condition. Also investigated
      were the influence of temperature on separation and the effect of organic
      modifier concentration on the dynamic exchange of the analytes between micelles
      and the bulk of the buffer solution. Direct UV was applied for detection of the
      fatty acids.

PMID- 10065970
TI  - Rapid detection of ornithine transcarbamylase activity by micellar electrokinetic
      chromatography.
AB  - A quantitative ultraviolet detection method for determining ornithine
      transcarbamylase (OTC-ase) activity using micellar electrokinetic chromatography
      (MEKC) is described. The method is based on the direct determination of
      citrulline formed upon enzymatic reaction. Using a background electrolyte
      consisting of 35 mM sodium tetraborate, pH 9.3, containing 65 mM sodium dodecyl
      sulfate (SDS), the peak of citrulline in the electropherogram was easily
      identified and integrated. This allowed us to determine the rate of formation of
      the reaction product and to calculate the kinetic parameter Km of the OTC-ase
      investigated. The capillary electrophoretic method developed was applied to the
      determination of OTC-ase activity in plasma samples for citrulline in the
      nanogram range.

PMID- 10065971
TI  - Electrokinetic chromatography of twelve monomethylbenz[a]anthracene isomers using
      a polymerized anionic surfactant.
AB  - A method for the separation of twelve monomethyl-substituted benz[a]anthracene
      isomers using poly-(sodium undecylenic sulfate) (poly-SUS) surfactant by means of
      electrokinetic capillary chromatography (EKC) is described. Several parameters
      such as concentration of acetonitrile (ACN), pH, as well as applied voltage were
      studied to optimize the EKC separation. ACN at a concentration of 35% v/v, 12.5
      mM phosphate-borate buffer, 30 kV with 0.5% w/v poly-SUS at a pH of 9.5 provided
      a resolution of a mixture of nine out of twelve methylbenz[a]anthracene (MBA)
      isomers in 50 min. The results of this study suggest that molecular length of MBA
      rather than length-to-breath ratio plays an important role in the elution order
      of some isomers.

PMID- 10065972
TI  - Polymers of sodium-N-undec-10-ene-1-oyl taurate and sodium-N-undec-10-ene-1-oyl
      aminoethyl-2-phosphonate as pseudostationary phases for electrokinetic
      chromatography.
AB  - The use of micelle polymers, a class of polysoaps with a polymerized hydrophobic
      interior and a charged hydrophillic exterior, as pseudostationary phases in
      electrokinetic chromatography has generated significant interest. Their stable
      structure has been shown to provide significant advantages over conventional
      micelles when used as pseudostationary phases. In previous studies, micelle
      polymers have had carboxylate and sulfate head groups. These chemistries have
      limitations: carboxylate micelle polymers precipitate out of solution at pH less
      than seven or eight and sulfate head groups are not stable to hydrolysis and are
      hydrolyzed during polymerization. Additionally, while the chemical selectivity of
      conventional micelles varies with head group chemistry, no significant
      differences in chemical selectivity were observed between analogous polymers with
      sulfate and carboxylate groups. To overcome the limitations of carboxylate and
      sulfate head groups, and to further investigate the chemical selectivity of
      micelle polymers, poly(sodium-N-undec-10-ene-1-oyl-taurate) and poly(sodium-N
      undec-10-ene-1-oyl-ethyl-2-phosphonate) micellar polymers have been synthesized
      and characterized as pseudostationary phases. These polymers have amide
      functionality and stable, strongly acidic sulfonate and phosphonate head groups.
      These polymers did provide improved solubility at low pH, and are stable under
      the conditions studied. The chromatographic performance and chemical selectivity
      of the polymers has been studied by several methods, including linear solvation
      energy relationships. Poly(sodiumN-undec-10-ene-1-oyl-taurate) has greater
      electrophoretic mobility than other polymers of this type, and can be used for
      the separation of hydrophobic compounds. The polymers do exhibit unique
      selectivity, but the differences in selectivity are not significant for the
      majority of compounds studied.

PMID- 10065973
TI  - Separation of enantiomers by capillary electrophoresis using pentosan
      polysulfate.
AB  - Pentosan polysulfate, a semisynthetic polysaccharide, was employed as a chiral
      run buffer additive in capillary electrophoresis. Twenty-eight racemic analytes
      were resolved. The separations were successful only at low pH when the analytes
      were significantly protonated. This suggests that ionic interactions were the
      dominant associative interactions between the anionic pentosan polysulfate and
      the positively charged analytes. Compared to other linear, carbohydrate-based
      chiral selectors (i.e., chondroitin sulfates, heparin and dextran sulfate)
      pentosan polysulfate has some characteristics common of anionic polysaccharides;
      yet it has several differences in its structure and properties which account for
      its unusual enantioselectivity. The effects of pH, concentration of phosphate
      buffer, concentration of pentosan polysulfate and the type and concentration of
      organic modifier on the enantiomeric separations were investigated. The
      optimization of these separations were dependent on the nature of the analytes
      and could be achieved by the proper choice of experimental conditions.

PMID- 10065974
TI  - Estimation of the pH-independent binding constants of alanylphenylalanine and
      leucylphenylalanine stereoisomers with beta-cyclodextrin in the presence of urea.
AB  - The separation of stereoisomers, particularly enantiomers, is important when
      their physiological activity differs. We have resolved the four stereoisomers
      each of alanylphenylalanine (Ala-Phe) and of leucylphenylalanine (Leu-Phe) by
      capillary electrophoresis using beta-cyclodextrin as a buffer additive and urea
      to enhance its solubility. A study of the influence of pH and beta-cyclodextrin
      concentration on the separations showed that weak inclusion complexes were formed
      between the dipeptides and chiral selector. It was found that pH could alter the
      migration order of enantiomers L-Ala-L-Phe and D-Ala-D-Phe, as well as L-Leu-L
      Phe and D-Leu-D-Phe; however, there was no change in order for the other pairs of
      optical isomers. Electrophoretic mobility data were used to estimate the acid
      dissociation constants of the dipeptide isomers at pH < 7 with no chiral selector
      present. By varying the concentration of beta-cyclodextrin, the chiral selector,
      the binding constants of Ala-Phe and Leu-Phe optical isomers in their fully
      protonated and zwitterionic forms were estimated. For the four Ala-Phe
      stereoisomers, K = 42-66 M(-1) and 4-41 M(-1) for the cationic and zwitterionic
      forms, respectively. For the four Leu-Phe stereoisomers, K = 43-94 M(-1) and 1-28
      M(-1) for the cationic and zwitterionic forms, respectively.

PMID- 10065975
TI  - Determination of association constants between enantiomers of orciprenaline and
      methyl-beta-cyclodextrin as chiral selector by capillary zone electrophoresis
      using a partial filling technique.
AB  - The principles for the determination of conditional association constants of
      enantiomers by capillary zone electrophoresis employing a partial filling
      technique (PFT) using methyl-beta-cyclodextrin as chiral selector is presented.
      Orciprenaline was used as a model compound. Partial filling is a separation
      technique, where different lengths of the chiral selector solution are introduced
      into the capillary to a final zone length shorter than the effective length of
      the capillary, prior to application of the solutes. Lengthening of the separation
      zone results in improving enantioresolution in addition to decreasing
      electrophoretic mobility of the enantiomers, because of longer interaction time
      between the solute and chiral selector. The degree of the reduction in
      electromobility depends on the affinity of the solute to the chiral selector,
      i.e. strength of the complex formed between the solute and cyclodextrin. The
      decrease in the electrophoretic mobility with increasing length of the separation
      zone is used for determination of the association constant. The association
      constants of the enantiomers of orciprenaline and the chiral selector were
      evaluated from the slope of the plot, observed electrophoretic mobility versus
      the ratio between the length of the separation zone and the effective length of
      the capillary. It was found that the association constants were independent of
      the chiral selector concentration. The mean values were 110 M(-1) and 160 M(-1)
      for respective enantiomer. Constants obtained by a conventional CE technique were
      in good agreement with those from the PFT experiments. The highest
      enantioselectivityy was obtained when about 50% of the solute was distributed to
      the selector phase.

PMID- 10065976
TI  - Enantiomer separation of drugs by capillary electrophoresis using mixtures of
      beta-cyclodextrin sulfate and neutral cyclodextrins.
AB  - Direct separation of enantiomers of drugs was investigated by capillary
      electrophoresis employing mixtures of charged cyclodextrin derivatives (CDs) and
      electrically neutral CDs (i.e., dual CD system). Among various charged CDs
      employed, it was found that beta-CD sulfate showed relatively wide
      enantioselectivity for a wide variety of drugs under acidic conditions. Then
      separation of enantiomers was performed by employing beta-CD sulfate and the
      effect of the addition of electrically neutral CDs to the buffers containing beta
      CD sulfate was investigated. Through the addition of electrically neutral CDs to
      the buffers containing the charged CD, resolution of most of the enantiomers was
      improved, compared with those with the charged CD alone. It was also found that
      the ring size (alpha, beta, gamma,), the substitution groups and the
      concentration of the additional electrically neutral CDs affected the
      enantioselectivity. For example, alpha-CD addition was effective for the
      separation of enantiomers of chlorpheniramine and hydroxypropyl-beta-CD was
      effective for the enantiomer separation of trimetoquinol isomer. The application
      of the method in optical purity testing is also briefly mentioned.

PMID- 10065977
TI  - Chiral resolution of atropine, homatropine and eight synthetic tropinyl and
      piperidinyl esters by capillary zone electrophoresis with cyclodextrin additives.
AB  - Chiral resolution of atropine, homatropine and eight synthetic tropinyl and
      piperidinyl esters were studied by capillary zone electrophoresis with
      cyclodextrin additives. Atropine and eight synthetic derivatives were
      successfully resolved by heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM-beta
      CD) at concentrations ranging from 10 to 40 mM. Homatropine was baseline resolved
      by 10 mM beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin (HP-beta-CD),
      respectively. The developed method was employed for the determination of atropine
      enantiomers in human serum.

PMID- 10065978
TI  - Simultaneous separation and enantioresolution of racemic local anesthetic drugs
      by capillary zone electrophoresis with Tween 20 and methyl-beta-cyclodextrin as
      selectors, employing a double plug technique.
AB  - A new approach for simultaneous chiral and achiral separations by capillary zone
      electrophoresis is described. Two adjacent selector plugs, consisting of Tween 20
      as an achiral and methyl-beta-cyclodextrin (CD) as a chiral selector, are
      employed and four related local anesthetics are used as model compounds. The
      principles of the partial filling technique, whereby the capillary is filled with
      the chiral selector solution followed by the micellar solution at different plug
      lengths and concentrations, prior to application of the solutes, was employed.
      During the run both capillary ends were dipped in a simple buffer, i.e., one
      without additives. The two separation media worked independently without any
      interaction. Separation of the solutes and their enantiomers was regulated by
      adjusting both the concentration and plug length (PL) of the micellar solution in
      the capillary, employing methyl beta-CD as chiral selector either at 38 or 76 mM.
      The solutes were separated on the basis of their affinity towards the micellar
      phase before they reached the methyl-beta-CD plug for enantioseparation. In the
      absence of the micellar plug, the enantiomers of prilocaine overlapped those of
      bupivacaine. The solutes and their enantiomers were completely separated by
      employing two adjacent plugs consisting of 100 mM Tween 20 solution (PL
      approximately 10 cm) and methyl-beta-CD solution at either 38 or 76 mM (PL
      approximately 30 cm).

PMID- 10065979
TI  - Chiral separation of lobeline analogs using high performance capillary
      electrophoresis and derivatized cyclodextrins as chiral additives.
AB  - High performance capillary electrophoresis (HPCE) methods are described that will
      separate the enantiomers of various lobeline analogs synthesized in these
      laboratories. "Cyclodextrin array analysis" was used for preliminary screening
      and electrophoresis conditions were optimized for each investigated analog. The
      lobeline analogs under consideration were investigated as potential nicotinic
      agonists for the treatment of neurodegenerative disorders, such as Alzheimer's
      disease. Native alpha (alpha)-, beta (beta)-, and gamma (gamma)-cyclodextrins,
      methyl-beta-cyclodextrin (M-beta-CD), heptakis-(2,6-di-O-methyl)-beta
      cyclodextrin (DM-beta-CD), and heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin
      (TM-beta-CD), hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) and hydroxypropl-gamma-cyclodextrin (HP-gamma-CD) were
      used as run buffer additives and their effect on the enantiomeric resolution of
      the lobeline analogs was investigated. The effect of pH, buffer concentration,
      voltage, temperature and organic modifier concentration on the enantiomeric
      resolution of the lobeline analogs was investigated. The most suitable conditions
      for each compound were chosen and, with detection at a wavelength of 200 nm,
      optimized.

PMID- 10065980
TI  - The advantages and limitations of permanent or reversible deactivation techniques
      in the assessment of neural function.
AB  - This review considers the different forms of reversible deactivation and how they
      differ from each other and from more conventional permanent deactivation methods.
      The different methods of chemical and cooling reversible inactivation and the
      limitations of each are discussed. Finally, future directions in the quest to
      localize brain function in the experimental animal are considered and how this
      work relates to emerging non-invasive imaging techniques presently being used
      with humans.

PMID- 10065981
TI  - Reversible inactivation of subcortical sites by drug injection.
AB  - Reversible inactivation of subcortical targets by means of drug injections has
      been a powerful tool for revealing the contributions of discrete brain structures
      to behavior and the functional organization of the brain. This paper is intended
      to provide practical advice on this approach, including the choice of drug, means
      of delivering drugs, strategies for evaluating the action of injected drugs, and
      the application of this method to experiments with awake animals.

PMID- 10065982
TI  - Spatial and temporal parameters of cortical inactivation by GABA.
AB  - Inactivation by GABA is a powerful tool for studying the function of specific
      cortical regions. It is especially useful in electrophysiology, because
      inactivation is reversible within short time periods, and because the extent of
      the inactivated region can be accurately controlled. Iontophoresis of GABA
      inactivates neurons up to 300 microm around the micropipette. Pressure injection
      of GABA inactivates neurons further away, but the spatial and temporal
      characteristics of inactivation by this method have been poorly studied. In order
      to address this question, we built devices made of micropipettes and
      microelectrodes glued at various distances. We experienced that repetition of
      small injections of 100 mM GABA inactivate cortex in a more homogenous way than
      bolus injections. Diffusion of GABA after pressure injection does not seem to
      follow a point spread diffusion model as in the case of iontophoresis: GABA
      probably goes up along the micropipette shaft, and the volume of inactivation has
      an ellipsoidal form. In order to precisely determine the extent of the
      inactivated region, we built a mathematical model to fit the experimental data of
      inactivations obtained above and below the pipette tip. The model provides
      estimates of the inactivated region for volumes smaller than 60 nl of GABA 100
      mM. Limits of inactivation are between 250 and 500 microm lateral to the tip of
      the pipette. The geometry of inactivation is difficult to predict beyond 60 nl
      and it seems hazardous to try to inactivate neurons beyond 800 microm with
      pressure injections of GABA 100 mM.

PMID- 10065983
TI  - Pharmacological inactivation in the analysis of the central control of movement.
AB  - In this review, we describe how pharmacological inactivation can be used to
      elucidate the central control of skilled limb movement. Local anesthetics and
      tetrodotoxin block neuronal cell bodies and passing fibers while gamma
      aminobutyric acid (GABA) and muscimol only block cell bodies. Blockade induction
      time is short (several minutes) for all the agents. Blockade duration produced by
      local anesthetics and GABA is 15-60 min, while that of tetrodotoxin and muscimol
      is up to several days. We describe our drug injection system, with an integrated
      microelectrode and a viewing port for visually monitoring drug flow into the
      injection cannula. We used glucose metabolism to assess the extent of
      inactivation. Intracortical lidocaine or muscimol injection produces a central
      core of maximal hypometabolism (1 mm radius), which could be due to drug spread,
      surrounded by an extensive region (several millimeters) of reduced
      hypometabolism, possibly due to reduced synaptic activity of neurons receiving
      projections from the core region. Drug injection only depresses neuronal
      activity, which contrasts with cooling, where there can be neuronal
      hyperexcitability at the periphery of the inactivation site. Our experiments in
      behaving animals show how pharmacological inactivation is an effective analytical
      tool for dissecting the differential functional contributions of subcortical and
      cortical forelimb representations to limb movement control.

PMID- 10065984
TI  - Corticofugal modulation of functional connectivity within the auditory thalamus
      of rat, guinea pig and cat revealed by cooling deactivation.
AB  - Microelectrode recordings were simultaneously performed at multiple sites in the
      medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We
      studied the effect of cortical deactivation on the association of neural activity
      within the thalamus during spontaneous activity. The corticofugal influence was
      suppressed by temporary cooling of the auditory cortex. Pairs of spike trains
      recorded from the same electrode were distinguished from cases where units were
      in MGB but recorded with different electrodes. Time domain analyses included
      crosscorrelations and search for precise repetition of complex spatiotemporal
      firing patterns of reverberating thalamic circuits. As a complementary approach
      we performed bispectral analyses of simultaneously recorded local field
      potentials in order to uncover the frequency components of their power spectra
      which are non linearly coupled. All results suggest that new functional neuronal
      circuits might appear at the thalamic level in the absence of input from the
      cortex. The newly active intrathalamic connections would provide the necessary
      input to sustain the reverberating activity of thalamic cell assemblies and
      generate low frequency non-linear interactions. The dynamic control exerted by
      the cortex over the functional segregation of information processing carried out
      in the thalamus conforms with theoretical neural network studies and with the
      functional selectivity-adaptive filtering theory of thalamic neuronal assemblies.
      Although this general conclusion remains valid across species, specific
      differences are discussed in the frame of known differences of the microcircuitry
      elements.

PMID- 10065985
TI  - The cryoloop: an adaptable reversible cooling deactivation method for behavioral
      or electrophysiological assessment of neural function.
AB  - We describe a very adaptable reversible inactivation technique for the behavioral
      or electrophysiological analysis of neural circuits. The cryoloop device can be
      permanently implanted or topically applied in an acute preparation to apply cold
      to discrete surface regions of the central nervous system (e.g. cerebral cortex
      or midbrain). The cryoloop consists of a custom shaped, stainless steel,
      hypodermic tubing and cooling is effected by passing chilled methanol through the
      lumen of the tubing. Cryoloop temperature is monitored by a microthermocouple
      attached to the union of the loop, and can be maintained within +/- 1 degrees C
      of a desired temperature. In chronic preparations, implanted cryoloops have been
      maintained in cats and monkeys for periods in excess of 2 years. After this
      period there are no structural, metabolic of functional changes in the
      deactivated tissue, and full reversibility of cooling-induced effects is
      maintained. Operation of multiple cryoprobes provides great flexibility of
      experimental protocols, permits double and triple functional dissociations to be
      made, and strengthens experimental design considerably.

PMID- 10065986
TI  - A method to assess the functional impact of cerebral connections on target
      populations of neurons.
AB  - We describe an innovative and tested approach combining two individually potent
      techniques to visualize simultaneously the functional impact of multiple
      projections on target populations of neurons in the brain. The rationale is
      simple: silence a defined set of efferent projections from one cortical region
      using cooling deactivation and then measure the impact of the deactivation on
      activities in multiple target regions using 2-deoxyglucose (2DG). This is a
      straightforward and sound approach because 2DG uptake by neurons reflects levels
      of underlying neural activity. All distant modifications evoked by the silencing
      of the set of efferent projections are examined in anatomical tissue and
      simultaneously for the multiple target sites to provide a global view of the
      functional impacts of the set of projections on the targets. With this method,
      downward adjustments of 2DG uptake levels identify removals of net excitatory
      signals, whereas upward adjustments identify net removals of suppressive
      influences. Future possible uses and modifications of the technique, including
      optical imaging, are discussed. Overall, the technique has the potential to
      provide fundamental, new measures on cerebral network interactions that both
      complement and extend current static models of cerebral networks and
      electrophysiological measures of functional impacts on individual neurons.

PMID- 10065987
TI  - Cerebral function revealed by transcranial magnetic stimulation.
AB  - Although transcranial magnetic stimulation (TMS) has been introduced only
      recently, it is safe and provides a painless, inexpensive noninvasive method for
      the evaluation of brain function. Determining central motor conduction time
      (CMCT) permits assessment of the corticospinal pathways. Mapping the central
      representation of muscles provides a method for investigating the cortical
      reorganization that follows training, amputation and injury to the central
      nervous system. Such studies of human plasticity may have important implications
      for neurorehabilitation. TMS also provides a method whereby cortical excitability
      can be noninvasively evaluated, which is likely to have important implications in
      the study of epilepsy, movement disorders and related conditions. TMS is useful
      in tracking the flow of information from one brain region to another and in
      investigations of cognition and functional localization, thereby complementing
      information obtained using functional imaging techniques, which have superior
      spatial but inferior temporal resolution. Finally, TMS is currently being
      investigated as a method for establishing cerebral dominance and as a therapeutic
      tool in the treatment of depression. Investigations for treatment of other
      neurologic and psychiatric conditions are likely to be undertaken.

PMID- 10065988
TI  - Imaging neuronal calcium fluorescence at high spatio-temporal resolution.
AB  - A rapid fluorescence imaging system was developed and utilised to investigate the
      time-course of intracellular calcium concentration ([Ca2+]i) gradients generated
      by action potentials in CA1-CA3 pyramidal cells within brain slices of the rat
      hippocampus. The system, which is based on a fast commercial CCD camera, can
      acquire hundreds of 128 x 128 pixel images in sequence, with minimal inter-frame
      interval of 2.5 ms (400 frames/s) and 12 bit/pixel accuracy. By synchronising
      patch clamp recordings with image capture, the timing of transmembrane potential
      variation, ionic Ca2+ current and Ca2+ diffusion were resolved at the limit of
      the relaxation time for the dye-Ca2+ binding reaction (approximately 5 ms at room
      temperature). Numerical simulations were used to relate measured fluorescence
      transients to the spatio-temporal distribution of intracellular Ca2+ gradients.
      The results obtained indicate that dye reaction-diffusion contributes critically
      to shaping intracellular ion gradients.

PMID- 10065989
TI  - Smoothing bandwidth selection for response latency estimation.
AB  - Stimulus response latency is the delay between stimulus onset and the evoked
      modulation in neural activity. A common technique to estimate latencies involves
      binning the spike arrival times to form a peri-stimulus histogram. This histogram
      is smoothed using a fixed bandwidth. The estimated latency is the first time
      following stimulus onset in which the smoothed histogram exceeds the midpoint
      between the minimum and maximum of the smoothed histogram. We demonstrate that
      the choice of smoothing bandwidth is critical to the accuracy of this latency
      estimation technique. We suggest a bootstrap resampling technique for bandwidth
      selection which results in a robust latency estimate.

PMID- 10065990
TI  - Subcellular distribution of delta-opioid receptors in the rat spinal cord: an
      approach using a three-dimensional reconstruction of confocal series of
      immunolabelled neurons.
AB  - Using a specific rat monoclonal anti-idiotypic antibody we have examined the
      subcellular distribution of -opioid receptors in various neuronal subtypes of the
      rat spinal cord. The immunofluorescence was detected with a confocal microscope
      and in some cases serial images were processed for a three-dimensional (3-D)
      reconstruction of the neurons. Immunolabelling was found to be distributed
      throughout the spinal cord grey matter specially in the most superficial layers
      of the dorsal horn, around the central canal and in the region of motoneurons of
      the ventral horn. The 3-D reconstruction made on large neurons of lamina IX in
      the ventral horn and on neurons of lamina X around the central canal allowed the
      visualization of 5 -opioid receptors in the cytoplasm of the soma and proximal
      neurites of immunofluorescent neurons. Some immunolabelled receptors were also
      detected at the level of the plasma membrane of the cell bodies and in the
      nuclear matrix. Interestingly, a particular arrangement of delta-opioid receptors
      organized along parallel alignments was observed on the plasma membrane of some
      neurons. This study emphasizes the potential usefulness of a 3-D reconstruction
      in the study of the spatial arrangement of cellular components.

PMID- 10065991
TI  - UV photolysis using a micromanipulated optical fiber to deliver UV energy
      directly to the sample.
AB  - UV photolysis of caged molecules is a powerful method for studying cellular
      signaling. However, UV energy is often delivered through the microscope objective
      which can make certain experiments difficult. We have evaluated the utility of
      delivering UV pulses directly to the sample through an optical fiber. Visible
      (635 nm) and UV (337 nm) lasers were coupled into a UV transmitting optical fiber
      which was micromanipulated over the sample under investigation. Positioning of
      the fiber, and thus the photolysis beam, was achieved using the visible laser
      which acted much like a flashlight. By controlling the size of the optical fiber
      it is also possible to control the area of the sample which is exposed to UV
      light. After positioning the fiber we demonstrate that the UV beam exiting the
      optical fiber reliably photolysed NP-EGTA that had been loaded into cells,
      resulting in an elevation of intracellular calcium. Additionally, caged
      norepinephrine in the bathing saline was photo-released to activate receptor
      operated calcium signaling pathways. Since the delivery of the UV energy is
      independent of microscope configuration, this approach can be readily
      incorporated into wide-field fluorescence imaging, confocal microscopy and
      electrophysiological applications.

PMID- 10065992
TI  - A simple microfluidic system for patterning populations of neurons on silicon
      micromachined substrates.
AB  - The purpose of this paper is to describe a low-cost simple technique based on the
      hydraulically driven deposition of adhesion molecules for patterning populations
      of neurons on silicon micromachined substrates. First, the design and fabrication
      process of the silicon micromachined substrates and the design of a flow-through
      chamber for the localised deposition of adhesive proteins are described. The
      experimental protocol for the deposition of the adhesive proteins is then
      presented. Finally, the results of experiments of 'entrapment' of chick embryo
      spinal cord neurons in microstructures of the silicon substrates and of formation
      of patterned biological neural networks are shown.

PMID- 10065993
TI  - The neurochip: a new multielectrode device for stimulating and recording from
      cultured neurons.
AB  - The neurochip is a silicon micromachined device upon which cultured mammalian
      neurons can be continuously and individually monitored and stimulated. The
      neurochip is based upon a 4 x 4 array of metal electrodes, each of which has a
      caged well structure designed to hold a single mature cell body while permitting
      normal outgrowth of neural processes. We demonstrate that this device is capable
      of maintaining cell survival, and that the electrodes can both record and
      stimulate electrical activity in individual cells with no crosstalk between
      channels.

PMID- 10065994
TI  - A reliable method for organ culture of neonatal mouse retina with long-term
      survival.
AB  - Organ culture systems of the central nervous system have proven to be useful
      tools for the study of development, differentiation, and degeneration. Some
      studies have been limited by the inability to maintain the cultures over an
      extended period. Here we describe an organ culture technique for the mouse
      retina. This method uses commercially available supplies and reproducible
      procedures to maintain healthy retinas with normal architecture for 4 weeks in
      vitro. The system is amenable to quantitative analysis. It can be used with both
      normal and retinal degeneration (rd) retinas to study of the role of various
      factors in photoreceptor degeneration in retinal cell fate determination and
      development.

PMID- 10065995
TI  - Methodology for coupling local application of dopamine and other chemicals with
      rapid in vivo electrochemical recordings in freely-moving rats.
AB  - Methodology is presented for constructing and using an electrode/microcannulae
      assembly that allows in vivo electrochemical measurements coupled with local
      application of dopamine (DA) and other chemicals in the unanesthetized freely
      moving rat. Rats were implanted with a voltammetric electrode constructed of a
      carbon fiber sealed in fused silica tubing attached to a pair of stainless steel
      guide cannulae, into which fused silica injection cannulae were inserted for
      local application of DA and other chemicals. Precise delivery of nanoliter
      volumes was accomplished using a syringe drive combined with a fluid swivel to
      deliver the solutions to the injection cannulae. A newly-designed miniature
      potentiostat connected to a commutator via a modular telephone jack assembly
      allowed for high-speed chronoamperometric electrochemical recordings in freely
      moving rats. Initial experiments characterized the in vitro electrochemical
      recording characteristics of the voltammetric electrode. In vivo studies were
      also carried out to study clearance of locally-applied DA and of potassium-evoked
      endogenous DA in the striatum and nucleus accumbens of freely-moving rats. In
      addition, the effects of chloral hydrate anesthesia on DA clearance signals in
      the nucleus accumbens were investigated. Moreover, the stability and
      reproducibility of this recording technique for measuring exogenous DA clearance
      was verified over a period of 5 days. Finally, the concurrent effects of systemic
      cocaine injection on DA uptake in nucleus accumbens and locomotor activity were
      examined. These studies support the conclusion that the methodology described
      herein allows for rapid chronoamperometric electrochemical recordings in freely
      moving rats with precise microapplications of DA and other chemicals combined
      with concurrent measures of animal behavior.

PMID- 10065996
TI  - Localisation of connective tissue and inhibition of autofluorescence in the human
      optic nerve and nerve head using a modified picrosirius red technique and
      confocal microscopy.
AB  - The use of picrosirius red to localise connective tissue in thin tissue sections
      viewed by bright-field microscopy is well documented. Its use on thin tissue
      sections imaged by fluorescence confocal microscopy has also been reported. Here
      we describe modifications to published procedures that allow picrosirius red
      staining of thick 60-microm sections and their subsequent analysis by confocal
      microscopy. The use of phosphomolybdic acid pre-treatment was found to be
      essential for confocal analysis; in addition to preventing non-specific staining,
      it also quenched tissue autofluorescence. By incubating sections free-floating,
      pre-treating them with phosphomolybdic acid for 30 min and imaging them using an
      argon ion laser we were able to use confocal microscopy to image the entire depth
      of 60-microm human optic nerve and nerve head sections stained with picrosirius
      red. The application of this modified picrosirius red and confocal microscopy
      technique should be useful for analysing the three-dimensional structure of the
      optic nerve and other tissues with a similarly complex arrangement of connective
      tissue.

PMID- 10065997
TI  - Adaptation of the circular platform spatial memory task for mice: use in
      detecting cognitive impairment in the APP(SW) transgenic mouse model for
      Alzheimer's disease.
AB  - A methodology is described for use of a 16-hole circular platform task to test
      spatial memory in mice. Both bright light and a fan were used to motivate mice to
      escape the platform surface through a single hole containing an attached escape
      box. For each daily trial, three correlated measures (escape latency, number of
      errors, and error rating) comprehensively evaluated cognitive performance. In an
      initial study, the 'spatial' nature of this task was demonstrated by the much
      poorer performance of non-transgenic mice when visual cues are removed.
      Behavioral sensitivity of the circular platform task was then shown through its
      ability to discern cognitive impairment in 7-month-old transgenic mice, carrying
      the mutant APP(SW) gene for early-onset Alzheimer's disease in humans, from non
      transgenic litter-mates. Since there are currently only a few tasks available to
      definitively test cognitive performance in mice, the circular platform task
      offers a versatile, multiple-measure option with numerous advantages.
      Particularly in view of the increasing number of genetically manipulated mouse
      models being produced, the circular platform task should be most useful in
      providing a sensitive evaluation of cognition in mice.

PMID- 10065998
TI  - Stable expression of human glycine alpha1 and alpha2 homomeric receptors in mouse
      L(tk-) cells.
AB  - We report the development of two mouse fibroblast-like stably-transfected cell
      lines (alpha1-62-4 and alpha2-B36-1) that express human alpha1 or alpha2 glycine
      receptor subunits, respectively. Transfected cDNAs were cloned into the pMSGneo
      expression vector, for which transcription is controlled by the dexamethasone
      inducible MMTV promoter. Patch-clamp electrophysiological recordings revealed
      that the alpha1 or alpha2 glycine receptor subunits expressed in these cells form
      functional glycine receptors that are inhibited by strychnine and picrotoxin.
      Glycine activated currents in these cells with EC50s of 101+/-7 or 112+/-23
      microM for cells stably expressing alpha1 or alpha2 receptors, respectively. As
      indicated by assays of glycine-stimulated 36Cl-- uptake, these cells express
      glycine receptors only after treatment with dexamethasone. In order to measure
      expression of the glycine alpha1 or alpha2 receptor protein, we produced a new
      anti-alpha1/alpha2 glycine receptor antibody (anti-alpha GR). Western blot
      analysis with this antibody showed a band of approximately 48 kDa only in
      homogenates from cells which had been transfected with the glycine alpha1 or
      alpha2 receptor cDNAs. Thus, through use of this stable expression system, we
      successfully produced cell lines expressing strychnine-sensitive glycine
      receptors that display similar functional characteristics to homomeric glycine
      receptors expressed in other systems. These stably transfected cells should
      provide a useful in vitro system for the study of the physiology and pharmacology
      of strychnine-sensitive glycine receptors.

PMID- 10065999
TI  - Novel method of chronically blocking retinal activity.
AB  - The ethylene-vinyl acetate copolymer Elvax has been used as a vehicle to deliver
      bioactive substances to discrete areas of the nervous system. Here we report a
      novel use of Elvax to chronically block retinal activity. Small pieces of Elvax
      containing the sodium channel blocker tetrodotoxin (TTX) were surgically
      implanted into the vitreous humor of ferret eyes. Observations of the light
      induced pupillary reflex combined with electrophysiological assays of vitreous
      humor confirmed that these implants completely blocked retinal activity for up to
      25 days without apparent retinal damage. The advantages of this procedure over
      previous methods requiring multiple daily injections of TTX, and alternative
      experimental applications are discussed.

PMID- 10066000
TI  - Silver staining method for demonstrating Lewy bodies in Parkinson's disease and
      argyrophilic oligodendrocytes in multiple system atrophy.
AB  - A reliable and economical silver staining method is recommended for demonstration
      of Lewy bodies (LB) and Lewy neurites (LN) in Parkinson's disease (PD) and of
      argyrophilic oligodendrocytes in multiple system atrophy (MSA). The technique can
      be applied to routinely formalin-fixed autopsy material and does not require
      particular skills. It permits processing of frozen sections and sections from
      polyethylene glycol or paraffin embedded material. It takes advantage of the
      physical development of nucleation sites and thereby permits tight control of the
      entire staining procedure.

PMID- 10066001
TI  - The World Health Organization International Consortium in Psychiatric
      Epidemiology (ICPE): initial work and future directions -- the NAPE Lecture 1998.
      Nordic Association for Psychiatric Epidemiology.
AB  - OBJECTIVE: To provide an overview of the World Health Organization (WHO)
      International Consortium in Psychiatric Epidemiology (ICPE), to introduce the
      World Mental Health 2000 (WMH2000) Initiative and to discuss methodological
      issues that the ICPE is grappling with in planning the WMH2000 Initiative.
      METHOD: We review the history, mission and organization of the ICPE and the
      rationale behind the WMH2000 Initiative. We review methodological research
      underlying major design and implementation decisions regarding the WMH2000
      surveys. RESULTS: The ICPE is an international consortium created to facilitate
      cross-national comparative epidemiological research using the WHO Composite
      International Diagnostic Interview (CIDI). The first-phase core ICPE surveys,
      which we are currently analysing, include over 33 000 interviews in seven
      countries, with an additional set of over 30 000 interviews in seven countries
      ready to be added to the master file within the next year. The WMH2000 Initiative
      will include a third series of CIDI surveys that include an anticipated 100000
      additional interviews in 10 countries. A series of complex methodological
      challenges confront us in designing and implementing the WMH2000 surveys. These
      include issues in the conceptualization and measurement of impairment and
      disablement, the implementation of standardized quality control procedures across
      countries, and the blending of epidemiological and clinical interviewing methods
      to obtain a valid cross-national characterization of disorder prevalences. Our
      current plans regarding these issues are discussed. CONCLUSION: Valid and
      representative general population epidemiological data on patterns, predictors
      and adverse consequences of psychiatric disorders are needed as a foundation for
      public health initiatives. The efforts of the ICPE promise to provide data of
      this sort for many regions in the world. Formidable methodological and logistical
      challenges arise in implementing this agenda, but we are confident that these
      challenges can be met by building on the firm foundation already established in
      the ongoing ICPE collaboration.

PMID- 10066002
TI  - Family burden and coping strategies in schizophrenia: are key relatives really
      different to other relatives?
AB  - Subjective and objective burden, psychiatric symptoms and coping strategies in a
      sample of 90 key relatives and other relatives of patients with schizophrenia,
      living in two European countries, were explored by means of well-validated
      questionnaires. The levels of burden on key relatives did not differ
      significantly from those on other relatives. Moreover, the risk of developing
      psychiatric symptoms was similar in the two subject groups at both centres.
      Significant correlations were found between key relatives and other relatives
      concerning the adoption of emotion-focused coping strategies. These data contrast
      with the current belief that family burden in schizophrenia is mainly a burden of
      key relatives, and they emphasize the need to provide supportive interventions
      for as many relatives as possible.

PMID- 10066003
TI  - Pubertal maturation and the development of behavioural and emotional problems in
      early adolescence.
AB  - Development of problem behaviour in early adolescence was predicted from change
      in pubertal stage and timing of pubertal development. Parent-reported (Child
      Behavior Checklist) and self-reported (Youth Self-Report) problem behaviour,
      pubertal stage and life events were assessed twice from a community sample of
      nearly 1300 Dutch children, aged 10-12 years at T1 and 12-14 years at T2.
      Pubertal change was a significant predictor of development in most parent
      reported problems. Once initial differences in problems had been accounted for,
      the slower the progress in pubertal development, the higher the problem score at
      T2. Development of self-reported problems was independent of pubertal change.
      Pubertal timing predicted development of two parent-reported and three self
      reported problem scales. Of the parent-reported problems, early maturation was
      associated with a decrease in boys' social problems and attention problems. Late
      maturing increased girls' social problems. Of the self-reported problems, early
      maturation was associated with an increase in girls' withdrawn and delinquent
      behaviour. Late maturing increased boys' attention problems. We conclude that
      pubertal development has small but significant effects on the development of
      problem behaviour in early adolescence.

PMID- 10066004
TI  - Measuring health status in psychiatric community surveys: internal and external
      validity of the Spanish version of the SF-36.
AB  - The aims of the present study were to determine the acceptability of the Spanish
      version of the Short Form (SF-36) health survey questionnaire for its use in
      mental health research on the general population, and to evaluate its internal
      and external validity, using data obtained from a representative community sample
      of 1250 adults of working age. The internal consistency of the different
      dimensions of the questionnaire was high. Concurrent validity was tested by
      examining its correlation with the 12-item General Health Questionnaire (GHQ-12).
      Construct validity was determined by studying the extent to which scores on
      different variables reflected the expected distribution of health status for and
      between certain groups. Our findings provide strong evidence for the
      acceptability and validity of the SF-36 when used as part of a community mental
      health survey.

PMID- 10066005
TI  - Psychopathy and psychopathological profiles in prisoners on remand.
AB  - A total of 178 Danish male remand prisoners were examined using comprehensive
      interviews and questionnaires on psychopathological, personality and social
      measures, and file data. These data were compared with scores on the Hare
      Psychopathy Checklist - Revised (PCL-R). Subjects were divided into four groups
      according to quartile PCL-R scores. In general there were high rates of
      psychiatric morbidity in all PCL-R quartile groups. The medium-high scorers
      represent a more vulnerable group with a high prevalence of dependence disorders,
      relatively high neuroticism score and relatively high prevalence of neurotic and
      stress-related disorders. The high scorers were more psychosocially maladjusted,
      had more often made previous suicidal attempts, and had a higher psychoticism
      score. Chronic psychotic disorders did occur, mostly in the high-scoring group.
      The population had lower scores on the PCL-R than in most previous studies,
      suggesting a lower prevalence of psychopathic features among Danish criminals and
      possibly a lower cut-off point when using the PCL-R as a categorical measure.
      Both findings are consistent with the results of other European studies. Further
      studies on cross-cultural differences with regard to PCL-R psychopathic features
      and on psychic vulnerability related to PCL-R scores and factor 1/factor 2 of the
      PCL-R are suggested.

PMID- 10066006
TI  - A prospective, long-term study of personality traits in patients with intractable
      obsessional illness treated by capsulotomy.
AB  - The crux when contemplating neurosurgery for otherwise intractable mental illness
      is whether there is a price which the patient may have to pay, in terms of
      adverse personality changes, for symptom relief. In the present study of 19
      patients undergoing thermo-capsulotomy for intractable obsessional illness,
      personality characteristics were studied pre-operatively, and at 1-year and 8
      year follow-up, using the Karolinska Scales of Personality (KSP). Small mean
      score changes toward normalization were apparent on all 15 KSP scales at the 1
      year follow-up, and significant improvements in anxiety proneness were noted at
      the 8-year follow-up. One patient who sustained a surgical complication showed
      deviant postoperative scores on scales related to psychopathic traits. There were
      no such deviant scores for the remaining subjects. The incidence of adverse
      personality changes following capsulotomy is low and does not increase with time.
      This conclusion, based on groups of patients, does not of course preclude the
      possibility that adverse personality changes may occur in individual patients.

PMID- 10066007
TI  - Comparative effects of low and high doses of clomipramine and placebo in panic
      disorder: a double-blind controlled study. French University Antidepressant
      Group.
AB  - This study was designed to explore the dose-response relationship for
      clomipramine in patients with panic disorder, with or without agoraphobia. After
      1 week of single-blind placebo pretreatment, 180 such patients were assigned to a
      multicentre placebo-controlled comparison of the effects of high and low doses of
      clomipramine, and were followed up for 8 weeks. In alleviating anxiety and panic
      disorder, both clomipramine doses were more efficacious than placebo for panic
      disorder and, to a lesser degree, for phobia. The lower dose was better tolerated
      and at least as effective as the higher dose, sometimes more so. These results
      indicate the clinically important possibility that low-dose clomipramine is
      effective and well tolerated.

PMID- 10066008
TI  - Long-term outcome of pharmacological and psychological treatment for panic
      disorder with agoraphobia: a 2-year naturalistic follow-up.
AB  - Two years after completion of a controlled outcome study of treatments for panic
      disorder with agoraphobia, patients were revisited and interviewed about their
      complaints. In the initial study, four treatments had been compared: (i)
      fluvoxamine combined with exposure; (ii) placebo medication plus exposure; (iii)
      psychological panic management plus exposure; and (iv) exposure alone. Comparison
      of the results at post-test had revealed superior efficacy of fluvoxamine
      combined with exposure over the other three treatments in reducing agoraphobic
      avoidance. The current naturalistic follow-up study investigated the long-term
      efficacy of the treatments with regard to abatement of complaints and reduced
      demand for further treatment. In addition, we examined whether patients were able
      to taper off the study medication without a recurrence of complaints. In total,
      71 of the 76 patients of the original trial (93%) were interviewed. Comparison of
      the mean level of psychopathology at follow-up revealed no difference between the
      original treatment groups. The effect in the fluvoxamine plus exposure group was
      maintained, but was no longer superior, due to further improvements in the other
      treatment groups. Most patients received additional treatment during the follow
      up period, usually because the 12 treatment sessions in the controlled study had
      yielded insufficient improvement. There was a trend for patients who received the
      fluvoxamine plus exposure treatment to require less aftercare than those who
      received the other treatments. Finally, almost 50% of the patients who had
      received medication in the original trial were able to taper off the use of
      fluvoxamine without a recurrence of complaints.

PMID- 10066009
TI  - Blunted TSH response to TRH and seizure duration in ECT.
AB  - The relationship between the thyrotropin (TSH) response to thyrotropin-releasing
      hormone (TRH) and the duration of seizures induced by electroconvulsive therapy
      (ECT) in depressed patients was investigated. In a balanced-order cross-over
      design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min
      before ECT in the first two sessions. In the third ECT session TRH was given just
      prior to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the
      duration of seizures, were measured. There was a significant inverse correlation
      between plasma TSH concentrations 20 min after TRH administration (deltaTSH) and
      seizure duration. Furthermore, when patients were categorized according to their
      TSH response to TRH, the group with blunted responses (deltaTSH <6 microIU/ mL, n
      = 7) had a longer seizure time during ECT than the group with non-blunted
      responses (deltaTSH > 6 microIU/mL, n = 9). Finally, the seizure duration in the
      group with blunted TSH responses was reduced significantly when TRH was co
      administered, while it remained unchanged in the group with non-blunted TSH
      responses. It is concluded that a blunted TSH response to TRH might indicate a
      seizure susceptibility as measured by the duration of seizures induced by ECT.
      The fact that TRH pre-administration had a reducing effect suggests that this
      substance might be involved in the pathophysiology of ECT-induced seizures.

PMID- 10066010
TI  - Changes in public attitudes towards mental illness in the Athens area (1979/1980
      1994).
AB  - Opinions about mental illness were measured, in 1994, in a probability sample
      consisting of 360 residents of two boroughs in greater Athens. These boroughs
      represent the catchment area of a community mental health centre. The aim of this
      study was to compare the differences in attitudes towards mental illness with a
      matched sample of 360 respondents drawn from the sample of the 1979/1980
      attitudinal study, conducted in the same area. The instrument used was the
      Opinion about Mental Illness scale, which yields five factors. In all five
      factors statistically significant differences between the two samples were
      observed. The recent study sample expressed more positive attitudes towards the
      social integration of the mentally ill, and did not favour the social
      discrimination against and restriction of mental patients. These results could be
      explained in the context of a positive and tolerant social climate in the Athens
      area, strengthened by the implementation of local community mental health
      intervention programmes.

PMID- 10066011
TI  - Apnea syndrome in a patient with Alzheimer dementia under chlormethiazole
      treatment: a clinical experience report.
AB  - Sleep apnea syndromes in conjunction with dementia have attracted considerable
      interest among geropsychiatrists in recent years. This clinical case report
      describes a demented and delirious elderly patient with a history of alcoholism
      who developed a sleep apnea syndrome under treatment with chlormethiazole. The
      risk of chlormethiazole treatment may be underestimated in vulnerable patients,
      e.g. those suffering from severe respiratory diseases or dementia. Alternative
      treatments for delirious states need to be evaluated instead.

PMID- 10066012
TI  - Removal of adherent ventricular catheter.

PMID- 10066013
TI  - Craniopharyngioma of the pineal region.
AB  - Craniopharyngiomas generally develop either in the suprasellar region or in both
      suprasellar and intrasellar regions. We report on a nontypical location of the
      craniopharyngioma in the pineal region. An 8-year-old boy was admitted to the
      department of pediatric neurosurgery in a grave condition. An MRI scan of the
      brain was performed after the neurological examination and revealed a large
      neoplasm situated in the posterior part of the III ventricle and in the pineal
      region, measuring 8.5x6.5x5 cm. The size of the tumor and its location meant it
      was occluding three ventricles, with subsequent hydrocephaly. Total removal of
      the tumor was carried out. Microscopic investigation of the tissue removed showed
      the typical structure characteristic for craniopharyngioma of the
      adamantinomatous type. Results of a consultation 6 months after the operation
      revealed that the patient was feeling well, attending school regularly and had
      finished the first semester with excellent results. On control MRI scan no tumor
      was found.

PMID- 10066014
TI  - Meningioma of the cavernous sinus in a child.
AB  - Intracranial meningiomas in children are rare, representing 1-4.2% of central
      nervous system tumors and 1.5-1.8% of all intracranial meningiomas. Meningiomas
      arising from the lateral wall of the cavernous sinus account for less than 1% of
      all intracranial meningiomas. To our knowledge, only one case of a meningioma
      arising from the cavernous sinus has been reported in childhood. A 6-year-old boy
      presented with left ophthalmoplegia. A slight drooping of the left eyelid was
      noted at the age of 1 year. Magnetic resonance imaging (MRI) with contrast
      administration revealed an enhancing mass lesion located in the left cavernous
      sinus. The tumor, arising from the lateral wall of the cavernous sinus, was
      totally removed and the oculomotor nerve was reconstructed with a sural nerve
      graft. MRI displayed total tumor removal 1 month after the surgery. The
      pathological diagnosis was of a psammomatous meningioma.

PMID- 10066015
TI  - Raised intracranial pressure in minimal forms of craniosynostosis.
AB  - Most cases of craniosynostosis are diagnosed during early infancy, but
      occasionally craniosynostosis evolves with minimal cranial involvement and goes
      unnoticed until late childhood. Seemingly these mild forms of craniosynostosis
      cause few, if any, symptoms of neurological involvement. We describe the cases of
      a 9-year-old girl and a 6-year-old boy who presented with evident signs of raised
      intracranial pressure (ICP), together with a negligible skull deformity. We have
      termed these cases as occult craniosynostosis. Differential diagnosis in our
      patients was established against known causes of benign intracranial
      hypertension. Bilateral expanding craniotomies afforded total relief from the
      symptoms and signs of raised ICP. Neurosurgeons treating children with symptoms
      and signs of benign intracranial hypertension should be aware of the possibility
      of minimal forms of craniosynostosis evolving with marked manifestations of
      raised ICP.

PMID- 10066016
TI  - Pediatric intramedullary spinal cord tumors. Critical review of the literature.
AB  - The objective of this review was to analyze the literature on the management of
      intramedullary spinal cord tumors to determine whether enough information was
      available for treatment guidelines to be established. Using standard computerized
      search techniques, databases containing medical literature were queried for
      keywords related to intramedullary spinal cord tumors, beginning in 1966. Of the
      445 articles published in English and with potential relevance, only 75 articles
      were included in the final analyses. Based on the strength of their
      recommendations for the treatment of this controversial condition, articles were
      divided into class I, class II and class III data. There were no class I studies
      related to any aspect of the treatment of intramedullary spinal cord tumors.
      Based on this critical review of literature, gross total removal of an ependymoma
      confirmed by immediate postoperative magnetic resonance imaging and adjunctive
      treatment for high-grade tumors using radiotherapy, with or without chemotherapy,
      can be recommended as standards of therapy. With the strength of a guideline,
      radiotherapy should be withheld after gross total removal of intramedullary
      ependymomas and radical resection of low-grade intramedullary astrocytomas. The
      use of intraoperative ultrasonography and evoked potentials, important surgical
      adjuncts, can also be considered guidelines. The radical resection of
      intramedullary low-grade astrocytomas is an option.

PMID- 10066017
TI  - Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective
      study.
AB  - Medulloblastoma is a common paediatric brain tumour, located in the cerebellum
      and in the IV ventricle, surpassed in frequency only by astrocytomas. 180
      children below the age of 15 with a medulloblastoma of the posterior fossa were
      treated in Denmark in the 25-year period from 1960 to 1984 and followed up until
      the end of 1996, or until death. During the 25 years they accounted for 20% of
      all intracranial tumours in children in Denmark. All tumours were histologically
      verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a
      factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the
      background population of children (1.05). The 5-year survival rate following
      diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was
      16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964,
      increasing to 36% in the last period 1980-1984. Presumably the increase in
      survival depends on many factors, e.g. improved diagnostic methods and
      neuroanaesthesia, better operative technique (microscope), improvements in
      radiotherapy and the introduction of chemotherapy. The best predictive factors of
      a good prognosis were preoperative CSF shunting, radical tumour removal and
      complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord.
      The survival rate in the last five-year period was seven times higher than the
      survival rate found in a comparable Danish study from the years 1935-1959. Most
      of the children followed Collins law of risk index. The results of treatment in
      children with medulloblastoma remain unsatisfactory. Accordingly, participation
      in international prospective studies of multimodal treatment should be
      encouraged, possibly using chemotherapy prior to surgery.

PMID- 10066018
TI  - Cerebrospinal fluid shunt infection in children: efficiency of management
      protocol, rate of persistent shunt colonization, and significance of 'off
      antibiotics' trial.
AB  - To evaluate the efficiency of our management protocol, 33 pediatric cases of
      bacteria-infected cerebrospinal fluid shunt were reviewed. The causative organism
      was staphylococcus in 23 patients. In 23 patients, shunt infection was managed
      according to the protocol. The complexity of the shunt system did not prolong
      hospitalization. Unchanged but externalized tubings showed persistent
      colonization despite adequate antibiotics in 10 of 21 patients. Staphylococcal
      infection was oxacillin-resistant in 7 of 19. The efficiency of an 'off
      antibiotics' trial was minimal. Further modification of the protocol is expected
      to enhance efficiency of the management.

PMID- 10066019
TI  - Predictors of seizure outcome following cortical resection in pediatric and
      adolescent patients with medically refractory epilepsy.
AB  - Several preoperative clinical variables have been reported to have value as
      predictors of seizure outcome following the surgical resection of epileptogenic
      focus in adults who have had medically refractory epilepsy. The present paper
      reports the results of a retrospective review of the ability of these variables
      to predict seizure outcome in a group of pediatric patients who had medically
      refractory epilepsy and underwent surgical resection of an epileptogenic focus at
      the Children's Hospital of Eastern Ontario. Variables in this review included age
      at first seizure, age at time of surgery, duration of seizures, seizure type,
      sex, family history, etiology, level of intelligence, EEG data, results of
      imaging studies, findings on examination of the central nervous system, and
      location and site of surgical resection. We found 64 patients who met the entry
      criteria for this review. Normal intelligence and tumor as etiology were
      associated with a good postoperative seizure outcome in patients who had a
      temporal resection; no variables had positive correlation with outcome in the
      extratemporal group. Caution must be used in the extrapolation of data and
      inclusion of studies of predictors of seizure outcome for adults to pediatric age
      groups.

PMID- 10066020
TI  - Epilepsy surgery for 5- to 18-year old patients with medically refractory
      epilepsy--is it cost efficient?
AB  - This study was designed to examine the question of whether cortical resection for
      children and adolescents with medically refractory epilepsy was less costly and
      more effective than the medical alternative. The study design used a decision
      analysis model. Data on outcome probabilities were based on literature review and
      local experience. The time span of the study was 25 years. Though the initial
      costs for the surgically treated group were significantly greater than those for
      the medical group, the time-cost lines intersected at 14 years after surgery.
      Surgery remained cheaper thereafter.

PMID- 10066021
TI  - Neuroendoscopic surgery for specific forms of hydrocephalus.
AB  - Neuroendoscopic surgery was used to treat patients with various forms of
      hydrocephalus with specific pathophysiology, including long-standing overt
      ventriculomegaly in adulthood (LOVA), isolated unilateral hydrocephalus (IUH),
      isolated IV ventricle (IFV), disproportionately large IV ventricle (DLFV),
      isolated rhombencephalic ventricle (IRV), isolated quarto-ventriculomegaly (IQV),
      dorsal sac in holoprosencephaly (DS), and loculated ventricle (LV). A total of 26
      operative procedures were performed, with neuroendoscopic surgery in 22 patients,
      12 with unique forms of noncommunicating hydrocephalus and 10 with various types
      of postshunt isolated compartment. These procedures included III ventriculostomy,
      aqueductal plasty by both rostral and caudal approaches, foraminal plasty in the
      foramen of Monro/foramen of Magendie, septostomy, IV ventriculostomy,
      fenestration of septation in the loculated ventricle, fenestration of arachnoid
      cyst or cystic tumor obstructing a ventricle with or without tumor removal, and
      dorsal sac ventriculostomy. The characteristics of the cerebrospinal fluid (CSF)
      dynamics in the individual specific pathophysiologies were delineated by cardiac
      gated cine-mode magnetic resonance imaging (MRI) before and after the endoscopic
      procedure. The consequent success rate (success = restoration of communication of
      the CSF pathway in the individual patients) was 19/22 (86.4%). The progression of
      ventricular dilatation was stopped in 17 of 19 patients (89.5%) in whom the
      endoscopic procedure was successful (radiologically arrested hydrocephalus).
      Improvement in the clinical symptoms and signs (clinically arrested
      hydrocephalus) was obtained in 15 of the patients (68.2% of all patients: 5 with
      LOVA, 3 with IQV, 5 with IUH and 2 with LV). Seven patients (2 LOVA, 2 IFV, 1 DS,
      1 DFLV and 1 IRV) underwent a shunt procedure after the neuroendoscopic
      procedure(s). The postoperative changes of ventriculomegaly were complicated,
      reflecting the differences in the brain parenchymal compliance and
      postoperatively corrected CSF flow dynamics in the major CSF pathway.

PMID- 10066022
TI  - An infantile intraosseous hematoma of the skull. Report of a case and review of
      the literature.
AB  - An infantile intraosseous hematoma of the right parietal bone is presented. This
      lesion appeared after birth trauma and persisted without any enlargement. It was
      diagnosed on the 25th day of life and the baby boy was operated on 2 weeks later.
      The clinical, radiological, surgical and pathological characteristics of this
      lesion are discussed.

PMID- 10066023
TI  - Molecular therapy for genetic muscle diseases--status 1999.

PMID- 10066024
TI  - To be or not to be an aggregate.

PMID- 10066025
TI  - Cloned mice raise possibility of human cloning.

PMID- 10066026
TI  - Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in
      females.
AB  - The aims of this study were to determine the prevalence of glucose-6-phosphate
      dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe
      the different mutations in the population, to determine its prevalence, and to
      study inheritance patterns in families of G6PD-deficient individuals. All infants
      born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were
      screened at birth for their G6PD status. In addition, those attending well-baby
      clinics during the period were also screened for the disorder. Families of 40
      known G6PD-deficient individuals, selected randomly from the records of three
      hospitals in the country, were assessed for G6PD deficiency. Where appropriate,
      this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%),
      comprising 15% of males and 5% of females tested, were found to be G6PD
      deficient. A total of 27 families were further assessed: of these, all but one
      family had the nt563 Mediterranean mutation. In one family, two individuals had
      the nt202 African mutation. The high manifestation of G6PD deficiency in women
      may be due to the preferential expression of the G6PD-deficient gene and X
      inactivation of the normal gene, and/or to the presence of an 'enhancer' gene
      that makes the expression of the G6PD deficiency more likely. The high level of
      consanguinity which, theoretically, should result in a high proportion of
      homozygotes and consequently a higher proportion of females with the deficiency,
      was not found to be a significant factor.

PMID- 10066027
TI  - Thalassemia carrier screening and prenatal diagnosis among the British Columbia
      (Canada) population of Chinese descent.
AB  - The goal of thalassemia screening is the identification, prior to the conception
      or birth of an affected child, of couples where both partners are thalassemia
      carriers. When both partners are identified as carriers for alpha- or beta
      thalassemia, the risk of having a fetus who is homozygous or compound
      heterozygous for the abnormal gene is 25%. A study was performed to identify
      whether routine screening for thalassemia is indicated for the Chinese population
      in British Columbia (BC). In a population of 783 subjects, studied either
      prospectively or retrospectively, 5.0% were alpha-thalassemia carriers and 1.7%
      were beta-thalassemia carriers. In addition, a review of all BC cases of prenatal
      diagnosis for thalassemia over a 6-year period indicated that 26% of couples were
      identified as alpha-thalassemia carriers because of a second or third trimester
      diagnosis of fetal hydrops, and 17% of couples referred for beta-thalassemia
      already had an affected child. The experience with prenatal diagnosis shows that
      a significant proportion of at-risk couples are not identified prior to or early
      in a pregnancy. The prevalence of carriers for thalassemia would warrant a
      program of education and routine screening for this condition in the BC Asian
      population.

PMID- 10066028
TI  - How do carriers of hemophilia and their spouses experience prenatal diagnosis by
      chorionic villus sampling?
AB  - A semistructured personal interview with 29 female carriers of hemophilia and 23
      of their spouses was performed at a median of 3 1/2 years after the first
      chorionic villus sampling (CVS) and gene analysis. Carriers with a hemophilic
      father or brother, had high sense of coherence (SOC) scores, and thus would be
      expected to have good ability to handle the stress of prenatal diagnosis (PD).
      Prenatal diagnosis of hemophilia by CVS was generally well accepted by the women
      and their spouses. However, the period while waiting for test results was
      experienced as emotionally troublesome by both the women and their spouses; women
      reporting significantly more psychiatric or psychosomatic symptoms than men.
      Positive effects resulting from participation by the spouse on how the women
      experienced PD could not be identified. Selective abortion after first trimester
      PD was clearly experienced as emotionally painful by both the women and their
      spouses, these reactions being similar to, but not as pronounced as those found
      after second trimester selective abortion. Notably, signs of depressive mood were
      observed several years after the abortion, and the provision of psychosocial
      support should be recommended for couples who decide upon termination of
      pregnancy following PD.

PMID- 10066029
TI  - Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected
      individuals.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition
      transmitted as an autosomal dominant trait with complete penetrance and variable
      expressivity. The syndrome is characterised by numerous basal cell carcinomas
      (BCCs), odontogenic keratocysts of the jaws, palmar and/or plantar pits, skeletal
      abnormalities and intracranial calcifications. In this paper, the clinical
      features of 37 Italian patients are reviewed. Jaw cysts and calcification of falx
      cerebri were the most frequently observed anomalies, followed by BCCs and
      palmar/plantar pits. Similar to the case of African Americans, the relatively low
      frequency of BCCs in the Italian population is probably due to protective skin
      pigmentation. A future search based on mutation screening might establish a
      possible genotype phenotype correlation in Italian patients.

PMID- 10066030
TI  - Lower extremity counterpart of the Poland syndrome.
AB  - Below-the-knee right leg hypoplasia and ipsilateral toe brachysyndactyly were
      observed in a 4-year-old female with an otherwise normal phenotype.
      Electromyographic and nerve conduction studies were normal. The Doppler
      evaluation was consistent with a 50% reduction in the blood supply from the
      femoral artery, suggesting vascular disruption as the pathogenic mechanism. Our
      observations support the hypothesis that a lower extremity counterpart of the
      Poland syndrome does exist and that the extent of limb involvement is dependent
      on the level of vascular disruption.

PMID- 10066031
TI  - Kenny-Caffey syndrome: an Arab variant?
AB  - We describe 2 unrelated Bedouin girls who met the criteria for the diagnosis of
      Kenny-Caffey syndrome. The girls had some unusual features--microcephaly and
      psychomotor retardation--that distinguish the Kenny-Caffey syndrome profile in
      Arab children from the classical Kenny-Caffey syndrome phenotype characterized by
      macrocephaly and normal intelligence. The 2 girls did not harbor the 22q11
      microdeletion (the hallmark of the DiGeorge cluster of diseases) that we
      previously reported in another Bedouin family with the Kenny-Caffey syndrome
      (Sabry et al. J Med Genet 1998: 35(1): 31-36). This indicates considerable
      genetic heterogeneity for this syndrome. We also review previously reported 44
      Arab/Bedouin patients with the same profile of hypoparathyroidism, short stature,
      seizures, mental retardation and microcephaly. Our results suggest that these
      patients represent an Arab variant of Kenny-Caffey syndrome with characteristic
      microcephaly and psychomotor retardation. We suggest that all patients with Kenny
      Caffey syndrome should be investigated for the 22q11 microdeletion. Other
      possible genetic causes for the Kenny-Caffey syndrome or its Arab variant include
      chromosome 10p abnormalities.

PMID- 10066032
TI  - Missense mutations in phosphomannomutase 2 gene in two Japanese families with
      carbohydrate-deficient glycoprotein syndrome type 1.
AB  - Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1) (MIM: 212065) is an
      autosomal recessive disorder with psychomotor retardation, strokelike episodes,
      ataxia, and olivopontocerebellar atrophy (OPCA) of neonatal onset. Recently, DNA
      substitutions in a gene for phosphomannomutase 2 (PMM2), mapped to 16p13, were
      identified in patients with CDG1. Biochemical findings in previously reported
      Japanese patients with CDG1 were slightly different from those of Caucasians,
      suggesting genetic heterogeneity of CDG1 in Japanese patients. We investigated
      the DNA sequence of PMM2 in two unrelated Japanese families with CDG1. Missense
      mutations in exon 5 (Phe144Leu) and exon 8 (Tyr229Ser, Arg238Pro) of the PMM2
      gene were present in two families, but they were not present in 72 unrelated
      healthy Japanese individuals. One of the missense mutations, Phe144Leu in exon 5,
      was common to two families with CDG1. Our findings confirm that mutations in the
      PMM2 gene account for at least some Japanese patients with CDG1 similar to that
      seen in Caucasians and that exons 5 and 8 are hot spots of mutations of CDG1
      caused by the PMM2 gene.

PMID- 10066033
TI  - X-inactivation and marker studies in three families with incontinentia pigmenti:
      implications for counselling and gene localisation.
AB  - Familial incontinentia pigmenti (IP) is an X-linked dominant disorder with an
      extremely variable clinical presentation. Ambiguous diagnosis can complicate
      genetic counselling and attempts to refine the gene location in Xq28. Marked
      skewing of X-inactivation patterns is a hallmark of IP and provides a means for
      investigating uncertain cases. We have conducted X-inactivation studies in three
      families where Xq28 marker studies were at odds with the original clinical
      assessment. The results indicate that no recombination between the disease locus
      and Xq28 loci has occurred and suggest that mosaicism is responsible for the
      discrepancy in one family.

PMID- 10066034
TI  - TGFA: exon-intron structure and evaluation as a candidate gene for Alstrom
      syndrome.

PMID- 10066035
TI  - Analysis of infertile brothers with congenital bilateral absence of vas deferens
      for mutations in the CFTR gene.

PMID- 10066036
TI  - Mutation in the factor V gene associated with inferior vena cava thrombosis in
      newborns.

PMID- 10066037
TI  - Genetic investigation of patients with hypercholesterolemia type IIa.

PMID- 10066038
TI  - Impact of ApoE4 allele on total cholesterol levels of children in northern Spain.

PMID- 10066039
TI  - Host cell glycosylation of viral glycoproteins--a battlefield for host defence
      and viral resistance.

PMID- 10066040
TI  - Comparison of 3 quantitative HCV RNA assays--accuracy of baseline viral load to
      predict treatment outcome in chronic hepatitis C.
AB  - The correlation between 3 assays for hepatitis C virus (HCV) RNA quantification
      and their respective accuracy in predicting the response to interferon and
      interferon/ribavirin therapy was evaluated by analysing pre-treatment sera from
      100 patients. A total of 97%, 100%, and 98% of the patients tested positive by
      the branched DNA 2.0 assay (Quantiplex), a multi-cycle reversed transcriptase
      polymerase chain reaction quantitative assay (Superquant) and the Roche Amplicor
      Monitor assay, respectively. The correlations between the assays, in all patients
      and in the major genotypes 1, 2, and 3, were significant, although the levels
      detected by the Amplicor Monitor assay were more than 1 log lower than by the
      other assays. Sustained virological responders to interferon therapy, but not to
      combination therapy, had lower baseline viral levels than long-term non
      responders (p = 0.002 by Quantiplex 2.0; p = 0.008 by Superquant; p = 0.06 by
      Roche Amplicor Monitor). Pre-treatment viral load greater than 3 x 10(6) Eq or
      copies/ml by the Quantiplex 2.0 and Superquant assays and greater than 100,000
      copies/ml by the Amplicor Monitor assay predicted long-term non-response in 94%,
      93% and 91% of the interferon treated patients, respectively. In conclusion,
      acceptable correlations between available commercial quantitative assays were
      found. High baseline viral load predicted long-term non-response to interferon
      monotherapy, whereas it did not to interferon/ribavirin combination therapy.

PMID- 10066041
TI  - Resistance to human cytomegalovirus infection may be influenced by genetic
      polymorphisms of the tumour necrosis factor-alpha and interleukin-1 receptor
      antagonist genes.
AB  - To examine whether there are genetic differences between cytomegalovirus (CMV)
      seronegative and CMV-seropositive adults, the polymorphisms of cytokine genes
      were analysed in a cohort of 400 adult blood donors. The genes and polymorphic
      sites studied were the tumour necrosis factor-alpha (TNF-alpha) gene (base
      exchange polymorphism at position -308; alleles TNF1 and TNF2) and the
      interleukin-1 receptor antagonist (IL-1RA) gene (variable numbers of 86-bp
      repeats in intron 2). In this material there were 85 (21%) seronegative persons.
      The frequencies of the TNF2 and the IL-IRA allele 2 (IL1RN*2) carriers were
      slightly increased in the seronegative compared with the seropositive samples
      (39% vs. 29%, and 55% vs. 47%, respectively). The presence of both of these
      alleles together was significantly (p < 0.05, chi2-test) more frequent in the
      seronegative population. These data suggest that the alleles of these cytokines,
      which are known to be associated with a strong inflammatory reaction, may have a
      protective role against CMV infection.

PMID- 10066042
TI  - Hepatitis G virus infection in haemodialysis patients and its relationship with
      hepatitis C virus RNA positivity.
AB  - A novel RNA virus designated hepatitis G virus (HGV) was identified recently in
      patients with acute and chronic liver disease. Since HGV may be transmitted
      parenterally, chronic haemodialysis (HD) patients are at increased risk for
      acquiring this infection. 110 chronic HD patients were studied (56 HCV-RNA and
      anti-HCV-positive, and 54 HCV-RNA and anti-HCV-negative). HGV-RNA and HCV-RNA
      were studied by RT-PCR. HCV genotype determination was applied to all 56 HCV-RNA
      positive patients. 28 of 110 (25%) patients were found be HGV-RNA-positive. HCV
      RNA-positive patients had higher rate of HGV-RNA positivity compared with HCV-RNA
      negative patients. The HCV genotypes of HGV-RNA-positive patients were mostly 4
      (48%) and 1b (33%). HGV was not linked with HBsAg positivity. While there was a
      significant correlation between HCV-RNA positivity and the number of blood
      transfusions and duration of HD, we did not observe this relationship in HGV-RNA
      positive patients. These results indicate that the prevalence of HGV is high in
      HD patients and that HGV-RNA positivity is higher in HCV-RNA-positive patients.

PMID- 10066043
TI  - Hepatitis C virus-infected, HCV-RNA-negative patients with bleeding disorders-
      relationship to age, HIV and treatment.
AB  - All 155 anti-hepatitis C-virus (HCV) positive patients with haemostatic disorders
      at our unit were tested for HCV-RNA in order to determine the prevalence of a
      negative result. The patients were also characterized in order to find predictors
      for a negative HCV-RNA test. The prevalence of a negative HCV-RNA test was 15.5%
      (24 of 155) and this was similar among anti-HIV positive and negative patients. A
      common denominator for the 4 HIV-infected, HCV-RNA negative haemophiliacs was
      treatment with azidothymidin prior to the first test. Among the anti-HIV negative
      patients, those < 40 y of age had a significantly greater chance of being HCV-RNA
      negative than the older ones (27.3 vs 3.6%). They also had a lower consumption of
      plasma products than age-matched HCV-RNA positive cases. Absence of co-infection
      with hepatitis B was not correlated with a negative HCV-RNA test. Young age and a
      low requirement for factor concentrates thus seem to be predictors for a negative
      HCV-RNA test in patients with bleeding disorders.

PMID- 10066044
TI  - Changes in small intestinal structure and function in HIV-infected patients with
      chronic diarrhoea.
AB  - Human immunodeficiency virus (HIV) is often combined with unexplainable diarrhoea
      and weight loss. This study was designed to see if changes in the intestinal
      mucosal structure could explain the malabsorption found in HIV-infected patients
      with diarrhoea. Twenty acquired immunodeficiency system (AIDS) patients, 19 men
      and 1 woman, CD4 < 0.01, with severe weight loss and with non-infectious chronic
      diarrhoea, were evaluated using a new intestinal function test (D-xylose breath
      test). Fifteen of the subjects were examined with an upper intestinal endoscopy
      with biopsy specimens taken from the duodenal mucosa. The function test showed
      that the D-xylose uptake was markedly decreased to the same extent as for
      patients with coeliac disease (breath index AIDS patients 9.4 (4.3-14.4), coeliac
      patients 15.6 (7.6-23.6), reference level 2.5 (2.4-2.9), urine excretion AIDS
      patients 20% (13-26), coeliac patients 22% (14-24), reference level 37% (32-42)).
      The severe malabsorption could not be explained by the slight mucosal changes
      occasionally seen by light microscopy with small mucosal inflammation and almost
      normal villi. However, electron microscopy showed enterocytes with signs of
      hypofunction and degeneration correlating better to the intestinal malabsorption
      found in patients with advanced HIV infection and chronic diarrhoea.

PMID- 10066045
TI  - Low faecal carrier rate of vancomycin resistant enterococci in Norwegian hospital
      patients.
AB  - The faecal carrier rate of vancomycin resistant enterococci (VRE) was surveyed
      among 616 patients in selected departments of 7 Norwegian hospitals. One
      Enterococcus gallinarum isolate harbouring a vanB2 element was recovered from a
      child with malignant disease treated with vancomycin and ceftazidime. No
      vancomycin resistant Enterococcus faecalis or Enterococcus faecium were detected
      and no VRE isolates of the VanA type were identified. The low level of VRE
      carriage corresponds to the limited use of glycopeptide antibiotics for human
      therapeutic purposes in Norway. It indicates a low risk of acquiring VRE
      infections in Norwegian hospitals.

PMID- 10066046
TI  - Pneumococcal endocarditis is not just a disease of the past: an analysis of 16
      cases diagnosed in Denmark 1986-1997.
AB  - To remind clinicians and clinical microbiologists of the clinical features and
      therapeutic aspects of pneumococcal endocarditis, patients with pneumococcal
      endocarditis from 1986 to 1997 were identified via an enquiry to clinical
      microbiologists across Denmark. For all patients records were reviewed to confirm
      the diagnosis of pneumococcal endocarditis, and the clinical course, therapy and
      outcome were analysed. 16 patients with definitive pneumococcal endocarditis were
      found. All pneumococcal isolates were sensitive to penicillin. 15 patients had no
      previously known cardiac valvular disease, 10 patients had X-ray-proven pneumonia
      and 5 had meningitis. The aortic valve was affected in 13 patients, of whom 12
      developed aortic insufficiency and 11 cardiac failure. Of 7 patients who
      underwent surgery, 6 needed immediate cardiac valve replacement. The 30-day case
      fatality rate was 19% (95% confidence limits 4-46%). Pneumococcal endocarditis
      must be considered when treating patients with pneumococcaemia. The most
      important clue to the diagnosis is a significant murmur and development of heart
      failure. Evaluation by transoesophageal echocardiography is helpful in
      determining the diagnosis and assessing the need for surgical intervention. With
      appropriate antibiotic therapy, close observation and cardiac valve replacement
      if necessary, the prognosis is better than recorded in earlier studies.

PMID- 10066047
TI  - Verotoxin-producing Escherichia coli (VTEC) infection in randomly selected
      population of Ilam Province (Iran).
AB  - In a randomly selected population, 2,008 fecal samples were screened for presence
      of Verotoxin producing Escherichia coli (VTEC) by colony sweep polymyxin-B
      extraction method. Non-sorbitol fermentation (NSF) phenotype and slide
      agglutination with O157: H7 antisera were used for screening and detection of
      this serotype. Ninety-eight (4.9%) fecal samples were found to be VTEC-positives
      and none of them belonged to the O157: H7 serotype. In rural areas, most
      individuals carrying VTEC isolates were asymptomatic, whereas in urban areas, a
      significant association was found between VTEC isolation and diarrhoea (p <
      0.01).

PMID- 10066048
TI  - Use of restriction enzyme analysis of amplified DNA coding for the hsp65 gene and
      polymerase chain reaction with universal primer for rapid differentiation of
      mycobacterium species in the clinical laboratory.
AB  - Two rapid procedures, restriction enzyme analysis of the amplified segment of the
      gene encoding for the 65000 mol. wt heat shock protein and a polymerase chain
      reaction with single universal primer (UP-PCR), were used for the identification
      of Mycobacterium tuberculosis complex (n = 47) and proving the species identity
      of non-tuberculous mycobacteria (NTM, n=36) cultured from clinical samples by
      comparing the resulting DNA banding pattern with patterns derived from
      mycobacterial type strains (n = 24). UP-PCR assay provided a rather wide limit of
      tolerance for variations in procedure. Although mycobacterial strains were found
      to generate species-specific banding patterns in both assays, M. tuberculosis and
      M. bovis strains and isolates produced nearly the same DNA patterns, which were
      very distinctive from that of all NTM tested. Investigation of the majority of M.
      fortuitum (n = 14) and M. kansasii (n = 7), mycobacteria most frequently causing
      mycobacterioses in the region, as well as other NTM isolates, showed reproducible
      patterns characteristic of corresponding type strains. Both methods combine the
      advantages of ordinary PCR and PCR 'fingerprinting', namely, the species-specific
      DNA pattern and primers applicable to different species. They may be applied as
      rapid tests for proving the identity of Mycobacterium species in a clinical
      laboratory.

PMID- 10066049
TI  - A blood micro-culture system for the diagnosis of bacteremia in pediatric
      patients.
AB  - The aim of this study was to evaluate the utility of a volume-modified blood
      culture system to diagnose bacteremia in newborns and infants. A total of 793
      paired blood cultures, obtained from 464 patients (173 newborns and 291 infants),
      were analyzed. Vacutainer tubes containing 18 ml supplemented peptone broth
      sodium-polyanethol-sulfonate were used as the gold standard, in comparison with a
      blood micro-culture system containing 1.8 ml of the broth. Prior to antibiotic
      treatment, 2.2 ml of blood was obtained from each patient; 0.2 ml was inoculated
      in a blood micro-culture tube and 2 ml in a routine tube. Sensitivity,
      specificity and predictive values were calculated. Microorganisms were isolated
      in 153 standard blood culture tubes and 151 blood micro-culture tubes. The
      sensitivity of the blood micro-culture system was 95%, specificity 99% and
      positive and negative predictive values 96% and 99% respectively. The sensitivity
      and specificity of blood micro-culture in neonates and infants is high. We
      recommend that this system be used for the diagnosis of bacteremia in newborns
      and infants in laboratories where manual systems are still in use.

PMID- 10066050
TI  - Prospective study of nosocomial fungal meningitis in children--report of 10
      cases.
AB  - Within an 8-year period, 10 cases of fungal nosocomial meningitis in children 0
      13 y old were prospectively identified, 3 caused by yeasts other than Candida
      spp. (Rhodotorula rubra, Aureobasidium mansoni, Clavispora lusitaniae) and 7 by
      Candida albicans. Seven patients survived. whereas 3 neonates with fungal
      meningitis (all due to C. albicans) died. Risk factors for fungal nosocomial
      meningitis included cancer (2 children), previous neurosurgery (2 children),
      cranial trauma (1 case) and prematurity with low birthweight (5 cases). All
      patients except 1 had received broad-spectrum antibiotics before onset of
      meningitis. In addition to yeasts, bacteria were isolated from CSF of 4 children.
      One child had additional fungaemia. Univariate analysis was used to compare 10
      cases of fungal to 91 cases of bacterial nosocomial meningitis. Except for
      concurrent bacteraemia, (60 vs 25.3%, P < 0.03), which was more frequently
      observed among fungal meningitis, there were no significant differences in risk
      factors, sequelae or outcome (mortality) between patients with fungal vs
      bacterial meningitis. A review of fungal meningitis reported within the last 20 y
      is included.

PMID- 10066051
TI  - Low incidence of candidaemia among neutropenic patients treated for
      haematological diseases.
AB  - Candida colonization and haematogenous infection were studied retrospectively in
      277 patients with haematological diseases by reviewing the microbiological
      reports of fungal surveillance and blood cultures over a 4-year period. Most
      patients (83%) were colonized by Candida and in the majority (68%) the same
      Candida species was isolated from at least 2 body sites. However, candidaemia was
      diagnosed in only 3 patients. During the same period invasive aspergillosis was
      diagnosed in 7 patients. Possible causes for the low incidence of candidaemia
      were fluconazole prophylaxis, empirical amphotericin B and strict indication for
      antibacterial therapy.

PMID- 10066052
TI  - Low levels of IgG antibodies against pneumocystis carinii among HIV-infected
      patients.
AB  - IgG antibodies against Pneumocystis carinii (P. carinii) were detected by an
      ELISA method using urea-extracted material from human and rat P. carinii as the
      antigen. Carbohydrate formed a major part of the antigen responsible for
      reactivity in the ELISA assay, since periodate treatment reduced the reactivity
      of most sera tested. Cross-reactivity between human and rat P. carinii was
      detected. However, human serum recognized antigens specific for human P. carinii.
      With the ELISA method IgG antibody levels were compared between blood donors (n =
      40), asymptomatic HIV-antibody positive patients (n = 30) and AIDS patients with
      (n=22) and without previous P. carinii pneumonia (PCP) (n=21). HIV-infected
      patients had significantly lower antibody reactivity against the microorganism
      compared with blood donors. Among HIV-antibody positive patients the highest
      antibody reactivity was seen in PCP patients. The antibody response to PCP was
      impaired, since an equal number of patients had an increase and a decrease in
      antibody reactivity. In conclusion, carbohydrate formed an important part of the
      P. carinii immunogenic antigen. Cross-reactivity between rat and human P. carinii
      was demonstrated, but reactivity was somewhat lower using antigen from rats. The
      antibody level was lower in HIV-infected patients and the ability to mount an
      antibody response to the infection was impaired, suggesting that the poor
      antibody response may contribute to the liability of HIV-infected patients to
      have PCP.

PMID- 10066053
TI  - IgG seroprevalence of Lyme borreliosis in the population of the Aland Islands in
      Finland.
AB  - This is a study of people living in Aland, a group of islands in the Baltic Sea
      between Finland and Sweden. 500 blood donors and 3,248 health service clients who
      did not have Lyme borreliosis were examined for Borrelia burgdorferi IgG
      antibodies. The method used was an ELISA containing a selection of diagnostic
      antigens to a Borrelia burgdorferi PKo strain. It was found that the distribution
      according to sex, age and titre values was identical in the 2 groups, which were
      therefore treated as one. 19.7% of all the sera was positive. The prevalence in
      men was 23.6%, and in women 16.7%. The prevalence rises with age, the highest
      prevalence being seen in men (44.7%) and women (37.0%) over 70 y of age. The data
      show that the Aland islands are strongly endemic for Lyme borreliosis compared
      with international levels of infection.

PMID- 10066054
TI  - Phlebotomus-transmitted toscana virus infections of the central nervous system: a
      seven-year experience in Tuscany.
AB  - Toscana virus (TOSv) is a recently discovered Phlebotomus-transmitted human
      pathogen involved in acute infections of the central nervous system (CNS)
      occurring during the summer in natural foci in Italy. The purpose of this
      prospective study was to investigate the role of this virus in 170 patients with
      meningitis-meningoencephalitis of suspected viral origin, admitted to the
      Departments of Infectious Diseases at the Siena Hospital from 1990 to 1996.
      Infections caused by tick-borne encephalitis virus (TBEv) and TOSv or other
      neurotropic viruses were routinely diagnosed by means of conventional virological
      methods. 89 cases were attributed to TOSv, about 10% of which were Europeans on
      vacation in Tuscany. All of the TOSv-positive cases were observed during the
      summer and were residents of hilly areas in Siena and its province at an altitude
      not above 500 m. An increase in the number of cases was observed over the years,
      with a higher incidence among younger people. The clinical picture was similar to
      that observed in other viral infections of the CNS. Evolution was benign in all
      cases; in 2 subjects symptoms and signs of encephalitis were present.

PMID- 10066055
TI  - Tick-borne encephalitis in eastern Croatia.
AB  - 92 patients treated for tick-borne encephalitis (TBE) in the Department for
      Infectious Diseases, University Hospital Osijek, over a 22-year period (1973
      1995) were analysed. The patients were mostly forestry workers. The appearance of
      the disease followed the biological activity of the tick, with the largest number
      of affected individuals recorded between April and August. TBE in eastern Croatia
      is a relatively frequent infectious disease, appearing almost every year. In a
      smaller number (9.8%) of cases the clinical picture was aseptic meningitis, while
      in the majority of patients (90.2%) it presented as an acute
      meningoencephalomyelitic form. The course was relatively severe in the majority
      of the patients analysed, with disturbances of consciousness (32.6%) and
      transitory neurological signs (61.9%). Three patients died (3.3%) in the early
      phase of the disease. A monophasic course dominated. The clinical and
      epidemiological data were compared with the cases described in other parts of
      Croatia and regional differences were seen in the severity of illness. These
      variations could be due to the previously hypothesized different virus subtypes,
      or to some other unknown factors.

PMID- 10066056
TI  - Lactoferricin of bovine origin is more active than lactoferricins of human,
      murine and caprine origin.
AB  - The antimicrobial peptide lactoferricin is generated by gastric pepsin cleavage
      of lactoferrin. We have examined the antimicrobial activity of lactoferricins
      derived from lactoferrin of human, murine, caprine and bovine origin with minimal
      inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)
      against E. coli ATCC 25922 and S. aureus ATCC 25923. We found that lactoferricin
      of bovine origin (Lf-cin B) was the most efficacious of the lactoferricins
      tested. By comparing the linear and cyclic Lf-cin B we found the cyclic peptide
      to be the most active. Lactoferricin B was moderately active against E. coli ATCC
      25922 and S. aureus ATCC 25923, but had no activity against P. mirabilis or Y.
      enterocolitica. Lf-cin B showed good activity against C. albicans, C. tropicalis
      and C. neoformans.

PMID- 10066057
TI  - Cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's lymphoma.
AB  - A case of cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's
      lymphoma (NHL) is reported. The patient underwent antimicrobial treatment and
      surgical debridement of a palatine lesion. Complete clinical recovery was
      achieved. The presence of actinomycosis may obscure and delay the diagnosis of
      NHL.

PMID- 10066058
TI  - Liver transplantation for endstage hepatitis C cirrhosis in a patient with
      primary hypogammaglobulinaemia.
AB  - Liver transplantation was performed in a patient with primary
      hypogammaglobulinaemia, chronic hepatitis C and hepatic failure. The immediate
      posttransplant period was uncomplicated. Owing to a stricture of the
      choledochojejunostomy the patient was reoperated with construction of a
      hepaticojejunostomy 11 months posttransplant. The patient remained hepatitis C
      virus (HCV) RNA-positive, with high and increasing levels of HCV. Liver biopsies
      demonstrated the recurrence of HCV. 14 months after the transplantation the
      patient developed severe diarrhoea caused by Cryptosporidium parvum. The
      infection did not respond to available therapeutic measures. He deteriorated with
      development of liver failure and died 18 months after the transplantation. The
      present case report illustrates the difficulties associated with organ
      transplantation in patients with primary hypogammaglobulinaemia.

PMID- 10066059
TI  - Chlamydia pneumoniae infection associated with multi-organ failure and fatal
      outcome in a previously healthy patient.
AB  - Chlamydia pneumoniae has been associated with respiratory infections and with
      cardiovascular disease. We describe here a patient with multi-organ failure and
      fatal outcome in whom C. pneumoniae was implicated as a causative agent.
      Serological analysis for C. pneumoniae was done by immunofluorescence.
      Immunohistochemistry was carried out with avidin-biotin peroxidase staining. The
      patient had pneumonia I month prior to death. C. pneumoniae was detected in the
      heart and lungs by immunohistochemistry at autopsy. The patient had an antibody
      pattern suggestive of current or chronic C. pneumoniae infection. Serological
      analysis for Legionella sp., Mycoplasma pneumoniae, CMV, EBV, enteroviral agents
      and markers for autoimmune disease were negative. The findings suggest C.
      pneumoniae as the aetiological agent in this case of multi-organ failure.

PMID- 10066060
TI  - Arthritis due to mycobacterium fortuitum.
AB  - Mycobacterium fortuitum is classified as a rapidly growing mycobacterium (RGM)
      according to the Runyon classification. RGM are increasingly being recognized as
      human pathogens. Joint infection due to M. fortuitum is a rare, but serious
      disease. This report describes a patient with acquired immunodeficiency syndrome
      (AIDS) and septic arthritis of the knee due to M. fortuitum in a previously
      normal joint with no history of surgery or intra-articular injections.

PMID- 10066061
TI  - Fluconazole therapy in Candida albicans spondylodiscitis.
AB  - A case of Candida albicans spondylodiscitis in a 20-year-old female liver
      transplant recipient is reported. The patient was successfully treated with
      sequential therapy with liposomal amphotericin B and fluconazole. A review of the
      literature showed 10 cases of Candida albicans spondylodiscitis successfully
      treated either with fluconazole alone or a sequential therapy with amphotericin B
      and fluconazole. If long-term amphotericin B therapy is not feasible, a prolonged
      course of fluconazole in a daily dose of 200-400 mg may be considered as an
      alternative.

PMID- 10066062
TI  - A rare case of cotrimoxazole-induced eosinophilic aseptic meningitis in an HIV
      infected patient.
AB  - A case of cotrimoxazole-induced meningoencephalitis in an HIV-infected patient
      without signs of AIDS is reported. The patient developed an apparently
      generalized seizure, of cotrimoxazole, 1 month after first taking a dose of this
      drug and a febrile coma after a second dose 3 weeks later. Lumbar puncture
      revealed eosinophilic aseptic meningitis. The patient quickly recovered without
      sequelae and was given antiretroviral therapy plus pentamidine aerosolized and
      pyrimethamine as prophylaxis for opportunistic infections. No other adverse
      effects were observed. The report describes the diagnosis of this case supported
      by a commentary, including a literature review.

PMID- 10066063
TI  - High-producer allele of tumour necrosis factor-alpha is part of the
      susceptibility MHC haplotype in severe puumala virus-induced nephropathia
      epidemica.
AB  - The biallelic polymorphisms in the tumour necrosis factor-alpha (TNF-alpha) gene
      promoter region were studied in patients with nephropathia epidemica (NE). The
      rarer TNF2 allele, associated with a high TNF-alpha producer phenotype, was more
      frequently found in hospitalized NE patients (42%) than in healthy controls (15%;
      p=0.0064). The putative role of TNF2 as an independent risk factor for NE is
      discussed.

PMID- 10066064
TI  - IPV-Vero vaccine induces a strong booster reaction and is well tolerated in
      adults.
AB  - A phase 1-2 trial was conducted in 48 adults to study safety and immunogenicity
      of an inactivated poliovirus vaccine produced using Vero cells (IPV-Vero).
      Participants received 2 intramuscular injections with IPV-Vero (40-8-32 D-Ag
      units) 4 weeks apart. IPV-Vero was well tolerated, and induced strong antibody
      responses in all participants. At least an 8-fold titre rise against all 3 types
      of poliovirus was found within 1 week of the first vaccination, indicating a
      strong secondary response in primed individuals. Two days after the first
      vaccination, there was no indication for such a booster reaction. The second
      vaccination 4 weeks after the first dose did not further increase antibody
      levels, indicating that an immune plateau had been achieved after the first
      vaccination. The second vaccination was not reactogenic despite the presence of
      these high pre-vaccination antibody levels. We conclude that IPV-Vero is well
      tolerated and strongly immunogenic in adults. In pre-immune adults 1 dose is
      enough to induce an impressive booster reaction.

PMID- 10066065
TI  - Lack of GB virus C/hepatitis G virus sequences in cerebrospinal fluid in patients
      with central nervous system infections.

PMID- 10066066
TI  - Endocarditis due to enterococcus faecalis: risk factors and outcome in twenty-one
      cases from a five year national survey.

PMID- 10066067
TI  - Prevalence of clostridium difficile toxin in kidney transplant recipients.

PMID- 10066068
TI  - Cyclin D1 in breast cancer.
AB  - Cyclin D1 protein plays an important part in regulating the progress of the cell
      during the G1 phase of the cell cycle. The cyclin D1 gene, CCND1, is amplified in
      approximately 20% of mammary carcinomas, and the protein is over-expressed in
      approximately 50% of cases. This has led to intensive study to ascertain whether
      cyclin D1 is a biological marker in breast cancer; however, the clinical work has
      produced unexpected results. Work in cell lines and in transgenic mice indicate
      that CCND1 is a weak oncogene and it was expected that, like c-erbB-2, over
      expression of cyclin D1 protein would be associated with a poor prognosis. Early
      immunohistochemical prognostic studies produced equivocal results but we, and
      others, have recently shown that strong staining for cyclin D1 is more likely to
      be seen in well differentiated, estrogen receptor positive carcinomas.
      Furthermore, we have found that over-expression of cyclin D1 is actually
      associated with a good outcome, both in terms of prognosis and response to
      endocrine treatment. Cyclin D1 is frequently over-expressed in ductal carcinoma
      in situ but not in benign breast disease, including atypical ductal hyperplasia;
      hence its expression appears to be closely linked with carcinogenesis. In order
      to help explain the apparent beneficial effects of cyclin D1 over-expression, a
      number of closely associated cell cycle proteins have also been evaluated,
      including the cyclin dependent kinase inhibitor p27, which blocks the activating
      effects of cyclin D1. Initial reports show that high levels of p27 are associated
      with a good prognosis and we have shown a positive association between p27 and
      cyclin D1 expression. These clinical results of cyclin D1 are an example of how
      information obtained from basic cell biology studies needs to be complemented by
      clinical studies to ascertain the true worth of a prognostic marker.

PMID- 10066069
TI  - Cyclins and breast cancer.
AB  - Cyclins are regulatory subunits for cyclin dependent kinases in the coordination
      of the cell cycle. Cyclins can also serve non-cell cycle functions, such as the
      transactivation of estrogen receptor by cyclin D. Evidence for the participation
      of the G1 cyclins D and E in breast cancer is summarized, including transgenic
      and knockout mice, transfections, and expression patterns in cohort studies.
      Overexpression of cyclin D has been reported in ductal carcinoma in situ (DCIS),
      and similar overexpression of cyclin E is suggested. Strategies to reduce cyclin
      expression are discussed as potential prevention efforts.

PMID- 10066070
TI  - Prognostic implications of expression of the cell cycle inhibitor protein
      p27Kip1.
AB  - Mitogenic and growth inhibitory signals influence the activity of a family of
      cyclin dependent kinases (cdks). p27 is an important cdk inhibitor, acting in G1
      to inhibit cyclin-cdks. As negative growth regulators, the cdk inhibitors may
      function as tumor suppressors. While the p16 gene plays a tumor suppressor role
      in cancers, p27 gene mutations have been identified only rarely. While high
      levels of p27 protein are expressed in normal human mammary epithelium, loss of
      p27 is frequent and is of independent prognostic significance in breast cancers.
      Low p27 is also a poor prognostic factor in colon, gastric, esophageal, lung, and
      prostate carcinomas, and enhanced proteasomal degradation may underlie loss of
      p27 in tumor cells. Loss of p27 has not been significantly correlated with tumor
      proliferation in a number of studies and may reflect alterations in
      differentiation and adhesion-dependent growth regulation germane to oncogenesis
      and tumor progression. Efforts to confirm the prognostic value of p27 are under
      way in a number of large breast cancer studies. These studies may also indicate
      whether loss of p27 in association with other traditional or novel markers has
      greater prognostic potential than each factor alone. p27 immunostaining is
      inexpensive and reliable and may become part of the routine histopathologic
      processing of tumors in the near future. Widespread application of p27 in
      prognostic testing will require greater uniformity in scoring techniques and
      determination of the cut off levels which distinguish individuals at high and low
      risk of cancer recurrence and death. Finally, the greatest utility of p27 may lie
      in the information it sheds on the biology of aberrant growth regulation in
      breast cancer and the potential to use this in the generation of novel
      therapeutic strategies.

PMID- 10066071
TI  - The type 1 growth factor receptor family: new ligands and receptors and their
      role in breast cancer.
AB  - The type 1 family of growth factor receptors, which consist of the epidermal
      growth factor receptor, c-erbB-2, c-erbB-3, and c-erbB-4, are expressed in normal
      breast ductal epithelial cells and in some breast cancers. Nine genes have now
      been identified which code for ligands. In some cases the genes are spliced into
      a series of proteins which differ in structure, but all retain an EGF-like
      element responsible for receptor recognition. The EGF receptor is expressed in
      normal breast and in some cancers, but is apparently reduced in expression in
      other cases. Cancers with EGF receptors appear to represent a greater threat to
      patients as in most studies they are associated with a shorter time to relapse
      and overall survival. The c-erbB-2 protein is overexpressed at very high levels
      in about one fifth of breast cancers and is indicative of poor prognosis. Other
      cancers may express lesser degrees of overexpression but it is not clear if this
      is biologically or clinically significant. The c-erbB-3 protein is expressed in
      normal breast epithelial cells and has been reported to be present at high levels
      in some cancers but at normal levels or at lower than normal levels in some
      others. The limited studies to date suggest that when measured on its own c-erbB
      3 expression is not predictive. c-erbB-4 is also expressed in normal breast and
      in some cancers but no studies have yet been performed to address whether it is
      associated with disease behaviour. In the future it is likely that a greater
      understanding of the function of this complex family of interacting proteins will
      assist in gaining the maximum predictive power from measurement of their
      expression in human breast cancer.

PMID- 10066072
TI  - c-erbB2 expression predicts tamoxifen efficacy in breast cancer patients.
AB  - c-erbB2 is a proto-oncogene that encodes the trans-membrane protein p185. This
      protein shares considerable sequence and structure homology with members of the
      epidermal growth factor receptor family and it is believed to cooperate with
      these receptors in the signal transduction process in order to control cell
      proliferation. Overexpression of c-erbB2, with or without gene amplification, is
      frequently found in breast cancer, and a body of evidence suggests it is
      implicated in the development of resistance to the antiestrogen tamoxifen.
      Scientific evidence strongly supports a correlation between c-erbB2
      overexpression and lack of efficacy of tamoxifen in both advanced and adjuvant
      settings. However, given the important therapeutic repercussion of this topic,
      further studies are required before c-erbB2 evaluation can be routinely used to
      select patients who are likely to benefit from tamoxifen administration.

PMID- 10066073
TI  - HER-2/neu as a predictive marker of response to breast cancer therapy.
AB  - Amplification of the HER-2/neu (c-erbB-2) gene resulting in overexpression of the
      p185HER-2 growth factor receptor occurs in approximately 25% of early stage
      breast cancers. HER-2/neu has been established as an important independent
      prognostic factor in early stage breast cancer in large cohorts of patients and
      in cohorts with very long (30 year) follow-up duration. New data are emerging to
      suggest that HER-2/neu may be useful not only as a prognostic factor but also as
      a predictive marker for projecting response to chemotherapeutics, antiestrogens,
      and therapeutic anti-HER-2/neu monoclonal antibodies. In this review we highlight
      recent data on HER-2/neu as a predictive marker of response to breast cancer
      therapy and discuss the clinical implications of this information. The difficulty
      in comparing results from different data sets due to the wide variety of reagents
      and technologies used to detect HER-2/neu amplification/overexpression in
      clinical specimens is also discussed. Finally, we report results from
      experimental models of HER-2/neu overexpression which have been used in an effort
      to understand the relationship between HER-2/neu and response to
      chemotherapeutics and antiestrogens in breast cancer.

PMID- 10066074
TI  - Prognostic and predictive value of p53 and p21 in breast cancer.
AB  - The prognostic and predictive value of p53 has been extensively studied in breast
      cancer. p53 serves a multifunctional role as a transcriptional regulator, genomic
      stabilizer, inhibitor of cell cycle progression, facilitator of apoptosis, and
      also perhaps an inhibitor of angiogenesis. Abrogation of its function should
      therefore lead to a more aggressive breast cancer phenotype and a worse clinical
      outcome, and indeed the preponderance of studies confirm this, with the risk of
      recurrence and death increasing by 50% or more if p53 is abnormal. Lack of
      unanimity of results may be due to differences in technique, study design, or
      population, as well as the subjectivity inherent in some approaches; however, the
      complexity and random nature of genomic change present in cancer cells may well
      also contribute to the lack of unanimity. Because many anticancer agents may
      exert a therapeutic effect through genomic damage and subsequent triggering of
      apoptosis, and because p53 can respond to genomic damage and facilitate
      apoptosis, it can be hypothesized that an intact p53 would predict sensitivity to
      therapy. Present data in breast cancer, however, does not clearly indicate that
      this is the case. There are several potential explanations. Study designs to
      accurately test the predictive value of a molecular marker are more exacting and
      difficult to achieve than prognostic studies. There may also be multiple
      alternative pathways, not involving p53, that play a part in determining the
      therapeutic effect of a treatment. The prognostic value of a downstream effector
      of p53 has also been assessed, though less extensively. p21 is transcriptionally
      upregulated by p53 and is an inhibitor of cyclin-dependent kinases and thus of
      cell cycle progression. Higher levels of p21 might indicate a more indolent type
      of breast cancer. However, data from a number of clinical studies is very
      conflicting, and at present p21 is not a promising prognostic factor in breast
      cancer.

PMID- 10066075
TI  - The urokinase plasminogen activator system as a target for prognostic studies in
      breast cancer.
AB  - The identification of patients at high risk of relapse is currently one of the
      most important issues in breast cancer research. However, the selection of high
      risk patients continues to be difficult due to the unpredictable course of this
      disease. Axillary lymph node status is currently recognized as the best clinical
      discriminant between good and poor prognosis, yet almost 30% of node-negative
      patients and 65% of node-positive patients will experience a relapse. Additional
      prognostic markers are therefore urgently needed. Since metastatic disease is the
      main cause of cancer patient morbidity and mortality, the measurement of
      molecules functionally involved in the regulation of tumor invasion and
      metastasis is attractive as a means to predict prognosis. Cancer invasion is a
      complex process in which degradation of the extracellular matrix plays a crucial
      role. This degradation is accomplished by the concerted action of several
      proteolytic enzyme systems, including generation of plasmin by the urokinase
      pathway of plasminogen activation, matrix metalloproteases, and other
      extracellular proteases. Increased expression and secretion of urokinase
      plasminogen activator (uPA) strongly correlates with the malignant phenotype of
      many types of cells, and the central role of uPA in tumor invasion is now well
      established. This review will focus on the prognostic impact of components of the
      urokinase plasminogen activation system in breast cancer with emphasize on
      methodological issues.

PMID- 10066076
TI  - Metalloproteinases and tissue inhibitors of metalloproteinases.
AB  - Because the proteolytic degradation of extracellular matrix is required for
      invasion and metastasis, it would appear that the important family of matrix
      metalloproteinases (MMPs) and their inhibitors (TIMPs) might be prognostic
      indicators of the invasive potential of a breast tumor. Nevertheless, there are
      few data demonstrating an independent prognostic value of any individual MMPs or
      TIMPs in primary breast cancer patients. It is possible, however, that the
      balance among levels of certain MMPs and their inhibitors will be more
      informative, since MMPs are clearly involved in paracrine tumor-stromal
      interactions and are associated with angiogenesis, which does appear to be
      prognostic.

PMID- 10066077
TI  - Matrix metalloproteinase inhibitors.
AB  - Matrix metalloproteinases (MMPs) are a family of enzymes responsible for the
      breakdown of proteins of connective tissue. Through this action they play an
      important role in growth, development and tissue repair. Recent studies also
      suggest that MMPs are utilised in cancer, facilitating both local tumour invasion
      and metastasis. Levels of certain MMPs such as stromelysin-3 and gelatinase are
      elevated in tumour-associated stroma compared to non-involved tissue. A series of
      synthetic low molecular weight MMP inhibitors have been produced. Early
      inhibitors were based on the peptide structure of collagen, although more
      recently non-peptide inhibitors have also been developed. The inhibitors are
      selective for the MMP family and are active at low nanomolar concentrations.
      Experiments in models of breast cancer have shown that MMP inhibitors can
      significantly reduce the growth rate of both primary and secondary tumours, and
      can block the process of metastasis. Several MMP inhibitors have now started
      clinical trials in patients with advanced malignancy. Although not the optimum
      setting for a tumouristatic agent, early results suggest this approach may be
      effective in slowing tumour growth. Trials in the adjuvant setting will provide
      the most important test of these inhibitors and should determine their potential
      to complement existing cytoreductive treatments and prolong survival.

PMID- 10066078
TI  - The 67 kDa laminin receptor as a prognostic factor in human cancer.
AB  - Different receptors for adhesion molecules, including the monomeric 67 kDa
      laminin receptor (67LR), are responsible for the interactions between tumor cells
      and components of the extracellular matrix that play an important role in tumor
      invasion and metastasis. Clinical data clearly demonstrate the importance of the
      67LR in the progression of a wide variety of tumors, including breast, lung,
      ovary, and prostate carcinomas and lymphomas. Indeed, data on more than 4000
      cases of different tumors from different organs studied by immunohistochemistry
      are all concordant with a role for the 67LR in invasiveness, metastasis, and even
      tumor growth. This receptor molecule appears to be unusual since the
      corresponding full-length gene encodes a 37 kDa precursor protein which, after
      acylation, dimerizes to generate the mature 67 kDa form. The primary function of
      the membrane receptor is to stabilize the binding of laminin to cell surface
      integrins, acting as an integrin-accessory molecule, although homology of the
      gene encoding the receptor precursor with other genes suggests additional
      functions. Studies conducted to define the structure, expression, and function of
      this laminin receptor represent a step toward developing therapeutic strategies
      that target this molecule. In particular, therapeutic approaches that
      downregulate expression of the receptor on tumor cells might lead to decreased
      tumor aggressiveness.

PMID- 10066079
TI  - Assessment of intratumoral vascularization (angiogenesis) in breast cancer
      prognosis.
AB  - The search for prognostic markers is important both to identify those patients
      with occult metastases and also to spare chemotherapy in those patients whose
      tumors have not developed the capacity for distant spread. Angiogenesis, the
      formation of new blood vessels, is necessary for breast cancer growth and
      metastasis. Good correlation has been demonstrated between intratumoral
      vascularization and outcome in patients with breast cancer. Intratumoral
      vascularization in human breast cancer can be measured by using standard
      immunohistochemical methods. Strict guidelines for scoring need to be followed.
      Although attempts are being made to automate the reading, visual scoring remains
      superior. We studied a population of women with small node-negative breast cancer
      who received no adjuvant therapy and have a median follow-up of 15 years. We have
      found intratumoral vascularization, as measured by microvessel count, to be an
      independent prognostic factor for disease-free survival. Low microvessel count
      identifies a group of patients with a 20 year disease free survival of 93%. The
      proportion of women with low microvessel count decreases with increase in tumor
      size and increases with patient age. But even in mammographically detected
      nonpalpable breast cancer, that is, the smallest breast cancer we currently
      detect, the majority already have high microvessel count. Intratumoral
      vascularization appears to be an early event that is necessary but not sufficient
      for metastatic progression. Microvessel count seems to be an excellent marker to
      identify patients with good prognosis because those with low microvessel count
      have a 93% disease-free survival irrespective of size, grade, or estrogen
      receptor status, but is less good at predicting those at high risk since the 20
      year disease-free survival is still 67-70% in those with high microvessel count.
      Thus, the higher risk group needs to be further stratified using additional
      prognostic factors.

PMID- 10066080
TI  - Clinical significance of angiogenic factors in breast cancer.
AB  - Growth, progression, and metastasis of breast cancer, as well as of most of the
      other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth
      factors and endogenous inhibitors of angiogenesis have been identified and
      sequenced, and experimental studies suggest that angiogenic activity of a tumor
      may result from downregulation of inhibitors of angiogenesis or up-regulation of
      endothelial growth factors. The mechanisms leading to the alteration of the
      balance between positive and negative modulators of angiogenesis are only
      partially known. We are at the beginning of research to identify the more active
      angiogenic factors in human breast cancer, and little information is presently
      available on their clinical significance. Preliminary results suggest that among
      the known angiogenic peptides, both vascular endothelial growth factor (VEGF) and
      platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD
      ECGF/TP) have promising prognostic and, perhaps, predictive value. No data are
      available on the clinical value of co-determination of positive and negative
      regulators of angiogenesis to look at the angiogenic balance of each single
      tumor. Only a few studies have assessed the role of endogenous inhibitors of
      angiogenesis in human breast cancer, with results available only on
      thrombospondin-1 and -2 (TSP-1, -2). Finally, the determination of some integrins
      such as alpha6 and alphavbeta3 and of some other endothelial-adhesion molecules
      seems to be of potential prognostic value. Recognizing which are the more
      biologically active positive and negative angiogenic factors is the key for the
      identification not only of new prognostic markers but also of targets for
      antiangiogenic therapy in human breast cancer.

PMID- 10066081
TI  - Insulin-like growth factors in human breast cancer.
AB  - IGF1 and IGF2 are circulating peptide hormones and locally-acting growth factors
      with both paracrine and autocrine functions. IGF1 and IGF2 signal through a
      common tyrosine kinase receptor, the insulin-like growth factor 1 receptor
      (IGF1R), and have mitogenic, cell survival, and insulin-like actions that are
      essential for embryogenesis, post-natal growth physiology, and breast
      development. The activities of IGF1 and 2 are tightly-regulated by a network of
      binding proteins and targeted degradation mechanisms. This complex regulatory
      system is disrupted in breast cancer, leading to excess IGF1R signaling. Evidence
      for this statement includes: a) breast cancers are infiltrated with IGF2
      expressing stromal cells; b) mannose 6-phosphate/IGF2 receptor (M6P/IGF2R) is
      mutated in breast cancer, leading to loss of IGF2 degradation; c) IGF1R is
      overexpressed by malignant breast epithelial cells, and in some cases IGF1R is
      amplified; and d) complex changes in IGF binding protein expression occur during
      breast cancer progression which most likely also affect IGF1 and 2 signaling. The
      clinical importance of these epigenetic and genetic changes has recently been
      stressed by the finding that IGF1R signaling alters the apoptotic response of
      breast cancer cells to genotoxic stress and, in addition, IGF1R activation
      sensitizes cells to estrogen by inducing phosphorylation of the estrogen
      receptor. As a consequence of these findings, we propose that IGF analysis of
      breast cancer samples should shift from prognostic studies to an evaluation of
      IGF ligands, receptors, and binding proteins as resistance/sensitivity markers
      for radiation, chemotherapy, and endocrine therapy.

PMID- 10066082
TI  - Molecular prognostic markers in breast cancer.
AB  - Based on the scientific literature, there are several molecular markers which
      might be used for the prognosis of breast cancer. Possible molecular prognostic
      markers are: BRCA-1, BRCA-2, p53, erbB oncogenes, loss of heterozygosity (LOH),
      chromosomal aberrations, microsatellite instability, transforming growth factor
      alpha (TGFalpha), and the multiple drug resistance (MDR) gene. In this chapter,
      we discuss the possible role of these prognostic markers in breast cancer.

PMID- 10066083
TI  - Prognostic significance of micrometastatic bone marrow involvement.
AB  - The present review focuses on the methodology and clinical significance of new
      diagnostic approaches to identify micrometastatic breast cancer cells present in
      bone marrow (BM), as a frequent site of overt metastases. Using monoclonal
      antibodies (mAbs) to epithelial cytokeratins (CK) or tumor-associated cell
      membrane glycoproteins, individual carcinoma cells can be detected on cytologic
      BM preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies
      have shown that the presence of these immunostained cells is prognostically
      relevant with regard to relapse-free and overall survival. The current interest
      in autologous bone marrow transplantation in patients with solid tumors further
      underlines the need for screening methods that allow the detection of minute
      numbers of residual tumor cells in the transplant. Although the development of
      new molecular detection methods based on the amplification of a marker mRNA
      species by the polymerase chain reaction technique is a very exciting area of
      research, the clinical significance of this approach needs to be demonstrated in
      prospective studies. The immunocytochemical assays may be, therefore, used to
      improve tumor staging with potential consequences for adjuvant therapy. Another
      promising clinical application is monitoring the response of micrometastatic
      cells to adjuvant therapies, which, at present, can only be assessed
      retrospectively after an extended period of clinical follow-up. The extremely low
      frequency of BM tumor cells greatly hampers approaches to obtain more specific
      information on their biological properties. The available data indicate that
      these cells represent a selected population of cancer cells which, however, still
      express a considerable degree of heterogeneity with regard to the expression of
      MHC class I antigens, adhesion molecules (EpCAM), growth factor receptors (EGF
      receptor, erb-B2, transferrin receptor), or proliferation-associated markers (Ki
      67, p120). Regardless of the detection technique applied, there is an urgent
      demand for large multicentre trials, in which standardized methods are related to
      specified clinical outcomes.

PMID- 10066084
TI  - Timing of surgery for primary breast cancer with regard to the menstrual phase
      and prognosis.
AB  - The hormonal milieu of the patient at the time of surgery may influence the
      prognosis of patients with primary breast cancer. Circulating unopposed estrogen
      is perhaps detrimental, while circulating progesterone may confer a survival
      advantage. This hypothesis has particular relevance to the timing of surgery in
      relation to the menstrual cycle. After all, the first 14 days of the menstrual
      cycle (follicular phase) are characterized by high levels of circulating
      unopposed estrogen, while circulating progesterone is present during the second
      14 days of the cycle (luteal phase). Several retrospective studies have shown
      that surgery during the follicular phase of the menstrual cycle results in a
      worse disease-free and overall survival. Randomized controlled trials addressing
      the effect of timing of surgery or neoadjuvant hormonal therapy on breast cancer
      mortality are urgently needed to confirm or refute the unopposed estrogen
      hypothesis. Such trials may provide important insights into the natural history
      of breast cancer, and a basis for significantly reducing breast cancer mortality.

PMID- 10066085
TI  - Time-dependence of hazard ratios for prognostic factors in primary breast cancer.
AB  - Some prognostic factors, such as steroid receptors, appear strongly related to
      outcome in early studies with short follow-up, but as follow-up matures the
      relationships appear to weaken. We investigated this phenomenon for several
      factors (tumor size, axillary lymph nodes, S-phase fraction, estrogen receptor
      (ER) status, and adjuvant therapy) in a large sample of breast cancer cases
      (N=2,873) with up to 17 years of follow-up for disease-free survival (DFS).
      Subjects in the study were identified from patients who had hormone receptor
      assays performed in our laboratory. Analysis of DFS included fitting a
      multivariate Cox proportional hazards model, testing for nonproportionality, and
      examining diagnostic plots. The assumption of proportional hazards was violated
      for several factors including ER, tumor size, and S-phase fraction. For ER, the
      hazard ratio was initially less than 1.0, indicating a good effect on prognosis,
      but increased at later times to values greater than 1.0, indicating a bad effect
      on prognosis. In contrast, the hazard ratios for tumor size and S-phase were
      initially high and decreased asymptotically toward 1.0 over time. Analysis of p53
      expression in a subset of cases yielded qualitatively similar results. We
      conclude that several standard prognostic factors (ER, tumor size, S-phase
      fraction) and possibly other investigational factors have important but
      nonproportional effects on hazard. It is likely that violation of proportional
      hazards is common and not limited to breast cancer. Failure to recognize
      violations of proportional hazards can lead to both over- and under-estimation of
      the effects of important prognostic factors.

PMID- 10066086
TI  - Circulating tumor markers in breast cancer: accepted utilities and novel
      prospects.
AB  - Detecting and/or monitoring changes in circulating tumor markers might assist in
      evaluating cancer risk, diagnosis, prognosis, or response to treatment. Several
      categories of circulating tumor markers have been investigated in breast cancer.
      These categories include classical tumor-associated antigens, such as CEA and CA
      15-3, markers of tumor biology, including markers of angiogenesis, adhesion, and
      invasion, and antibody response to tumor-associated antigens such as HER2/neu and
      p53. We used a recently proposed Tumor Marker Utility Grading System to evaluate
      the use of several circulating tumor markers for different clinical utilities in
      breast cancer. While there are no tumor markers with established clinical
      utilities for most uses, tumor-associated antigens can be used for monitoring
      patients with metastatic disease. In addition, markers of tumor biology such as
      the circulating extracellular domain of HER2/neu might be useful in determining
      not only prognosis, but also response to specific treatments. However, further
      investigations are required to further assess the utility of individual tumor
      markers for specific clinical uses.

PMID- 10066087
TI  - The relationship between prognostic and predictive factors in the management of
      breast cancer.
AB  - The discovery of new prognostic factors proceeds at a much more rapid pace than
      our knowledge of how to properly utilize this information in the management of
      patients with breast cancer, especially those with early breast cancer that has
      not metastasized to regional lymph nodes. Prognostic factors provide information
      on how the patient is likely to do regardless of treatment. Predictive factors
      provide information on whether a patient is likely to benefit from therapy. Most
      factors identified to date provide prognostic information, but relatively few
      provide information that is truly helpful in making a therapeutic decision in the
      management of individual patients. In large part this is because there has been
      insufficient study of the factor, especially prospective evaluations of the
      factor. Unfortunately this has resulted in the premature use of this information
      under the general rubric that patients with a poor prognosis deserve more
      treatment in spite of the fact that there may be no benefit from that therapy in
      the poor prognostic group.

PMID- 10066088
TI  - Methodological challenges in the evaluation of prognostic factors in breast
      cancer.
AB  - Many studies are carried out in an effort to find factors that help explain the
      large unexplained variation in prognosis of breast cancer patients. The
      principles of good study design and analysis are less well appreciated for
      prognostic factor studies than for therapeutic trials. The oncology literature is
      full of results from studies of varying quality, often with conflicting findings.
      As a consequence, despite the large number of studies, there is still uncertainty
      about the importance of most prognostic factors. Few recently proposed prognostic
      factors for breast cancer have become widely accepted. This paper reviews the
      important methodological issues underlying such research. These issues are
      illustrated with examples from published studies and recent reviews of papers
      published in cancer journals. Guidelines are proposed for conducting and
      evaluating prognostic factor studies which should improve the quality of research
      in this important area.

PMID- 10066089
TI  - Assessing the clinical impact of prognostic factors: when is "statistically
      significant" clinically useful?
AB  - Very few tumor markers have been recommended for routine clinical care of
      patients with breast cancer. A framework to determine the clinical utility of
      tumor markers is required. In a previous publication, a "Tumor Marker Utility
      Grading System" (TMUGS) was proposed. TMUGS included a semi-quantitative grading
      scale (0-3+) which can be used to assign a score to a given tumor marker for a
      given outcome. Only those markers that are felt to be sufficiently strong to
      influence a therapeutic decision that results in improved clinical outcome for
      the patient are recommended. The studies from which data are used to assign a
      TMUGS grade can be placed into one of five Levels of Evidence (LOE). An extension
      of TMUGS ("TMUGS-Plus") is now proposed in which the relative strength of a
      prognostic or predictive factor can be estimated and expressed in terms of a risk
      ratio (RR) for prognostic factors or benefit ratio (BR) for predictive factors.
      Three categories of prognostic factors and three categories of predictive factors
      are proposed (strong, moderate, and weak). It is recommended that only LOE type I
      studies (prospective, highly powered studies of the tumor marker, or meta
      analysis of LOE II or III datasets), be used to estimate the RR or BR of a given
      factor. Finally, a matrix, based on assumptions of acceptable absolute benefits
      relative to risks, is proposed in which any given tumor marker can be assessed
      for its clinical utility. TMUGS-Plus should aid in the assessment of published
      data regarding clinical utility of tumor markers. Perhaps more important,
      clinical investigators can use TMUGS-Plus to design tumor marker studies that
      will fulfill criteria for clinical utility, resulting in more rapid acceptance of
      tumor markers for routine clinical use.

PMID- 10066090
TI  - Prognostic variables in node-negative and node-positive breast cancer.

PMID- 10066091
TI  - Transformation of rat glioma cells with the M-CSF gene inhibits tumorigenesis in
      vivo.
AB  - Macrophage colony-stimulating factor (M-CSF) is a potent stimulator of the
      effector cells such as monocytes and macrophages. To evaluate the effect of M-CSF
      on malignant gliomas, we transfected the rat gliosarcoma cell line (9L) with
      human M-CSF expression vector (pCEF-MCSF) by a liposome method. Transfectants
      were selected using G418-containing medium. As a control, 9L cells transfected
      with pRc/CMV and selected by G418 were used. The effects of M-CSF gene
      transfection on tumor cell proliferation in vitro and in vivo were examined. All
      growth rate did not change in vitro. While the control 9L cells formed
      progressively enlarging masses, 9L cells transfected with the M-CSF gene did not
      develop into tumors after the injection into rats. On the other hand, in rats
      receiving anti-asialo GM1 antibody, 9L cells transfected with M-CSF gene
      developed into tumors, though at a slower rate than control 9L cells. Histologic
      examination after transplantation of 9L cells transfected with M-CSF gene
      disclosed intense infiltration of macrophages in the tumor. Thus M-CSF gene
      transfection into glioma cells stimulates an antitumor effect.

PMID- 10066092
TI  - Adenovirus mediated gene therapy in a glioblastoma vaccine model; specific
      antitumor immunity and abrogation of immunosuppression.
AB  - Clinical trials are being performed using tumor genetically engineered to produce
      cytokines as a vaccine. The design of such a vaccine may be made more effective
      by further study using in-vitro as well as in-vivo models. We studied an in-vitro
      tumor 'vaccine' model in glioblastoma. We have demonstrated high efficiency
      transfection of the Interleukin-2 (IL-2) gene into glioblastoma cell lines using
      adenoviral vectors. Glioblastoma cell lines transduced with this vector could
      produce high levels of IL-2 for up to 2 weeks, long enough to elicit an antitumor
      immune response. We studied tumor/effector cell interactions using cytotoxicity
      assays coupled with flow cytometric analysis. Activation of CD8+ and expansion of
      CD3+/CD16+ effector cell subpopulations were observed, suggesting the generation
      of a specific anti-tumor response and the potential for systemic immunity. We
      demonstrated that glioblastoma produce immunosuppressive factors which reduce the
      antitumor response by peripheral blood effector cells. These immunosuppressive
      factors could be neutralized to improve antitumor response. A better
      understanding of tumor/effector cell interactions may improve the design of gene
      therapy trials.

PMID- 10066093
TI  - Urokinase induces receptor mediated brain tumor cell migration and invasion.
AB  - The plasminogen activation (PA) system plays an important role in tumor invasion
      by initiating pericellular proteolysis of the extracellular matrix (ECM) and
      inducing cell migration. Malignant brain tumors overexpress PA members and
      characteristically invade by migrating on ECM-producing white matter tracts and
      blood vessel walls. To determine whether urokinase-type plasminogen activator
      (uPA) and its receptor (uPAR) directly modulate the migration of brain tumor
      cells, we examined six human brain tumor cell lines, 2 astrocytomas (SW1088,
      SW1783), 2 medullobastomas (Daoy, D341Med), and 2 glioblastomas (U87MG, U118MG),
      for their surface uPAR expression, endogenous PA activity, and functional
      proteolytic activity by an ECM-degradation assay. Migration on Transwell
      membranes and invasion of Matrigel was then tested by pre-incubating the cells
      with increasing concentrations of either uPA, the proteolytically inactive amino
      terminal fragment (ATF) of uPA, or the uPAR cleaving enzyme, phosphatidylinositol
      specific phospholipase C (PI-PLC). All of the cell lines, except D341Med, express
      surface uPAR protein and uPA activity. High levels of uPAR and uPA activity
      correlated with cellular degradation of ECM, cell migration, and Matrigel
      invasion. Cell migration and invasion were enhanced by uPA or ATF in a dose
      dependent manner, while PI-PLC treatment abolished the uPA effect and inhibited
      migration and invasion. We conclude that ligation of uPAR by uPA directly induces
      brain tumor cell migration, independent of uPA-mediated proteolysis; and in
      concert with ECM degradation, markedly enhances invasion. Conversely, removing
      membrane bound uPAR from the surface of the cells studied inhibited their ability
      to migrate and invade even in the presence of proteolytically active uPA.

PMID- 10066094
TI  - Determination of lung as the primary site of cerebral metastatic adenocarcinomas
      using monoclonal antibody to thyroid transcription factor-1.
AB  - Determining the primary site of a cerebral metastatic adenocarcinoma is
      complicated by the histologic similarity of most adenocarcinomas. Thyroid
      Transcription Factor-1 (TTF-1) is a highly specific marker of peripheral airway
      cell neoplasms. Formalin fixed tissue from 30 patients with brain metastasis
      whose primary sources were clinically and histologically known with certainty
      were analyzed for immunoreactivity to TTF-1. There were 18 cases of metastatic
      lung adenocarcinoma. Other metastases were from breast (6), colon (1), prostate
      (1), kidney (1), paranasal sinus (1), melanoma (1), and intestinal carcinoid (1).
      No patients with carcinoma of the thyroid were found. Positivity was regarded as
      intense nuclear reactivity. Twelve (67%) metastatic lung adenocarcinomas stained
      for TTF-1. None of the cerebral metastases from other body sites showed
      positivity. In addition, normal brain tissue and astrocytic tumors did not stain
      for TTF-1. These data show that TTF-1 is a highly specific and reasonably
      sensitive marker for peripheral airway cell metastasis to the brain.

PMID- 10066095
TI  - Soluble CD95 (Fas/APO-1) in malignant glioma: (no) implications for CD95-based
      immunotherapy?
AB  - CD95 targeting is a novel approach of immunotherapy for malignant glioma that
      might be antagonized by the release of soluble CD95 by the tumor cells. An
      alternatively spliced CD95 mRNA that encodes a secreted CD95 variant has been
      detected in glioma cell lines in vitro and in human tumors in vivo. Here, we
      report that the levels of soluble CD95 in the serum of malignant glioma patients
      do not differ from those of lumbar disk disease patients. Soluble CD95 was
      detected in the CSF in 2 of 20 malignant glioma patients by ELISA. Bioassay
      studies indicate that these low levels of soluble CD95 in the CSF of some
      patients with malignant glioma cells are unlikely to interfere with CD95-based
      immunotherapy of malignant gliomas in vivo.

PMID- 10066096
TI  - The significance of the expression of tumor suppressor gene DCC in human gliomas.
AB  - Deleted in colorectal carcinoma (DCC) gene has been as a candidate of tumor
      suppressor genes, has been identified recently and is thought to relate to the
      metastatic potential in some cancers. We examined the gene in 60 human gliomas
      (26 glioblastomas multiforme (GBMs), 16 anaplastic astrocytomas (AAs), 6 low
      grade astrocytomas (LGAs) of WHO Grade II, and 11 recurrent gliomas) and A172
      human GBM cell line by reverse transcription polymerase chain reaction (RT-PCR).
      Twenty (77%) GBMs, 11 (69%) AAs, and 1 (17%) LGA revealed the reduced or absent
      DCC expression. Reduced DCC expression was also shown in 10 (91%) recurrent
      gliomas. Furthermore, in 5 cases with both primary and recurrent GBM, the DCC
      expressions of all recurrent tumors were lower than those of primary tumors. No
      significant correlation between DCC expression and Mib-1 labeling index was
      confirmed. The survival rate of patients without reduced DCC expression was
      significantly superior to that of patients with reduced DCC expression in overall
      malignant astrocytic tumors. In GBM and AA separately, DCC expression also tended
      to correlate with patient's prognosis. These results suggest that reduced DCC
      expression is an important marker in tumor malignancy and recurrence in
      astrocytic tumors and that may be a useful prognostic factor in patients with
      malignant astrocytic tumors.

PMID- 10066097
TI  - Alleletyping of an oligodendrocyte-type-2 astrocyte lineage derive from a human
      glioblastoma multiforme.
AB  - We have conducted alleletyping of two novel cell lines derived from glioblastoma
      multiforme, which appear to have arisen from different glial lineages, by using
      76 fluorescently labeled oligonucleotide primers amplifying microsatellite loci
      covering the entire human genome. One cell line, Hu-O-2A/Gb1, expresses antigens
      and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0
      2A) lineage of the rat central nervous system. This cell line generated, in
      vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and
      astrocytes. The second cell line, IN1434, is derived from an astrocyte or a
      precursor cell restricted to astrocytic differentiation. Hu-O-2A/Gbl cells show
      allelic losses of loci on chromosomes 2, 5, 6, 7, 8, 9, 10, 11, 13, 15, 16, 17,
      20 and 21. IN1434 cells are likely to have allelic losses of loci on chromosomes
      1, 3, 8 and 10, although no control DNA is available for this cell line. These
      results, for the first time, provide a detailed information of the molecular
      genetic defects occurring in Hu-O-2A/Gb1 and IN1434.

PMID- 10066098
TI  - Thallium-201 SPECT as response parameter for PCV chemotherapy in recurrent
      glioma.
AB  - Combination chemotherapy with procarbazine, CCNU and vincristine (PCV) may be
      effective in patients with recurrent glioma. Response monitoring is mandatory,
      but radiological response evaluation is often difficult. We evaluated Thallium
      201 (201Tl) SPECT as a response parameter in ten patients treated with intensive
      PCV chemotherapy for recurrent glioma. 201Tl-SPECT studies showed early changes
      (decreasing volume and intensity) in nine patients and these changes were more
      pronounced than radiological findings. 201Tl-SPECT results after completion of
      chemotherapy seemed to correlate with clininal findings during follow up. We
      conclude that 201Tl-SPECT may contribute to the assessment of response in
      patients treated with PCV chemotherapy for recurrent glioma.

PMID- 10066099
TI  - Increased proliferative activity due to necroses induced by pre-operative
      embolization in benign meningiomas.
AB  - The proliferative behaviour of 35 benign intracranial meningiomas was
      investigated which were embolized for devascularization 3 to 268 hours prior to
      surgical exstirpation. The nuclear proliferation antigen Ki-67 was visualized by
      means of the monoclonal antibody MIB1 on formalin fixed and paraffin embedded
      tissue. Tumor cells and inflammatory reactions were recognized by means of
      conventional staining procedures and by immunohistochemical detection of HAM56,
      LCA, HLA-DR, CD15-epitope and vimentin. Extravasation and proliferation of
      granulocytes, macrophages, lymphocytes and the degree of expression of MHCII
      antigens was estimated according to a 7-point ordinal scale. Confirming
      preliminary observations of others the proliferation index within the
      perinecrotic tumor rim (PIperinec) exceeded that of intact tissue highly
      significantly. PIperinec peaked at the third to fourth day after embolization and
      kept this level until the seventh day. The time course of PIperinec was
      paralleled by that of macrophages, whereas--expectedly--granulocytes occured
      earlier and lymphocytes and HLA-DR-positivity somewhat later. The timely
      relationships suggested that the perinecrotic increase in tumor cell
      proliferation was mainly due to macrophage-born mitogens. Perinecrotic
      proliferative activity in embolized meningiomas does not reflect genuine tumor
      proliferation and should not be used for assessment of the presence or degree of
      malignancy in a given tumor.

PMID- 10066100
TI  - Central nervous system atypical teratoid tumor/rhabdoid tumor: response to
      intensive therapy and review of the literature.
AB  - Central nervous system atypical teratoid/rhabdoid tumor (ATT/RT) of infancy and
      childhood is a unique histologic entity with an extremely aggressive natural
      history. Standard therapy for infant and childhood medulloblastoma, for which
      this entity is often mistaken, has been ineffective; most children survive less
      than 12 months after diagnosis. Intensified therapy has been recently used for
      children with this disease, with promising results [1,2]. We report four cases of
      ATT/RT in young children; all had subtotal resections and localized disease at
      diagnosis. One child treated prior to bone marrow transplant availability died of
      progressive disease 9 months after diagnosis. Another child, treated with high
      dose chemotherapy and radiotherapy in preparation for bone marrow transplant, had
      a recurrence and died 20 months after diagnosis, without undergoing the
      transplant. Two children received high-dose chemotherapy and autologous bone
      marrow transplant and had a good response to treatment; one survived 19 months,
      the other child is free of disease 46 months from diagnosis. Intensified therapy
      has altered the natural history of central nervous system ATT/RT.

PMID- 10066101
TI  - The pathogenesis of cysts accompanying intra-axial primary and metastatic tumors
      of the central nervous system.
AB  - Recent reports have suggested that cyst formation accompanying astrocytomas in
      the central nervous system (CNS) is due to an edematous process caused by blood
      brain barrier (BBB) disruption and not a result of necrosis. This study is
      performed to investigate whether the hypothesis of cyst formation based on BBB
      disruption also applies to various pathologically different intra-axial
      gliomatous tumors and metastases. By chemical analysis, using immunokinetic
      nephelometry, isoelectric focussing, cellulose acetate electrophoresis and a
      biuretic method, the concentrations of albumin, immunoglobulin G (IgG), IgA,
      alpha2-macroglobulin, IgM and total protein were measured and proportions of
      concentrations of these proteins were compared in cyst fluid, blood plasma and
      cerebrospinal fluid (CSF). Our data, based on the chemical analysis of cyst fluid
      and blood plasma of 37 patients, including 2 ependymomas (one cerebral; one
      thoracic), 3 oligodendrogliomas, 4 hemangioblastomas, 5 cerebellar astrocytomas
      and 1 cervical, 1 giant astrocytoma grade one, 1 gangliocytoma, 1 neuroblastoma
      and 19 metastases (five lung-; two renal-; three breast-; one melanoma-; one
      thyroid metastasis and seven metastases of unknown origin) present high protein
      concentrations in the cysts with a highly similar spectrum of proteins in the
      tumor cyst fluid and blood plasma, suggesting a BBB disruption followed by
      exudation of plasma proteins into the brain parenchyma with formation of edema
      and transition of edematous tissue into a cyst accompanying the tumor. Although
      histopathologically different types of tumor tissue are involved, data suggests
      that the pathogenesis of cysts accompanying gliomatous tumors and metastases in
      the CNS is based on BBB disruption and consequent edema, as is the case in the
      formation of cysts in anaplastic astrocytomas.

PMID- 10066102
TI  - Development of a simple, portable carbon dioxide incubator for in vitro
      production of bovine embryos.
AB  - The objective of this study was to develop a simple and portable CO2 incubator
      using effervescent granules (EG) and to examine the effect of negative and
      positive air pressure for in vitro maturation (IVM), fertilization (IVF) and
      culture (IVC) of bovine oocytes. In experiment 1, cumulus-oocyte complexes (COCs)
      were matured (22 h), fertilized (5 h) and cultured (7 days) using 0.25, 0.5 or
      1.0 g of EG per 0.6 l added to maintain an optimum level of CO2 (approximately 3,
      6 or 12%, respectively) for in vitro production of embryos. Control oocytes,
      zygotes and embryos were cultured in a standard CO2 incubator. The blastocyst
      production rates observed on Days 7 to 9 after insemination were 20.5+/-4.2%,
      18.5+/-3.9% and 28.7+/-5.1% for the 0.25 g EG, 0.5 g EG treatments and control,
      respectively. These rates were significantly higher (P < 0.05) than that of the
      1.0 g EG treatment (8.7+/-2.6%). The number of cells in the inner cell mass (ICM)
      and trophectoderm (TE) produced from blastocysts using the control procedure were
      40.8+/-2.9 and 81.2+/-5.3, respectively, and were higher (P < 0.05) compared to
      the 0.50 g EG (34.6+/-2.9 and 66.8+/-5.7) and 1.0 g EG treatments (33.4+/-3.4 and
      67.2+/-7.3). In experiment 2, COCs were placed in a small box with 0.25 g of EG
      so that the effects on IVM, IVF and IVC of positive or negative air pressure
      could be compared. The blastocyst production rate observed in the negative air
      pressure treatment (29.6+/-4.6%) was higher (P < 0.01) than that of the positive
      air pressure treatment (6.2+/-1.5%) or the normal treatment pressure (P < 0.05;
      18.7+/-4.2%) but did not differ from that of the control (30.7+/-4.4%). These
      results indicate that this simple type of incubator with negative air pressure
      can be successfully used for in vitro production of bovine embryos and could be
      used at the field level.

PMID- 10066103
TI  - Relative efficacy of conventional sperm parameters and sperm penetration bioassay
      to assess bull fertility in vitro.
AB  - Frozen semen samples from 10 bulls were thawed and actively motile sperm
      recovered using a swim-up technique. Calcium ionophore A23187 at 0.5 microM
      concentration was used for 1 min to induce the acrosome reaction in the sperm.
      Mature female golden hamsters were superovulated with 50 IU of equine chorionic
      gonadotrophin followed 56 h later with 75 IU of human chorionic gonadotrophin.
      The cumulus mass was recovered 17 h after hCG treatment by puncturing the
      oviducts in the infundibulum region. Subsequently, cumulus cell mass and zona
      pellucida were digested by 0.1% hyaluronidase and 0.1% trypsin, respectively, to
      yield zona-free hamster eggs (ZFE). A sperm penetration bioassay was performed by
      coincubating capacitated sperm at 5 X 10(6) concentration and ZFE for 3 h at 38
      degrees C in an air incubator. The conception rate of the bulls was based of an
      average of 82.6 cows per bull with pregnancy status confirmed by rectal
      palpation. It was found to be strongly correlated (p < 0.01, r = 0.723) with
      fertilization percentage, whereas percent motile sperm, percent viable sperm and
      percent sperm with intact acrosomes were not significantly correlated with the
      conception rate (r = 0.210, -0.021 and -0.468, respectively). Results of the
      present study suggest that the sperm penetration bioassay can be reliably used to
      test the fertilizing potential of bull sperm in vitro.

PMID- 10066104
TI  - The relationship between plasma oestrone sulphate concentrations in pregnant
      dairy cattle and calf birth weight, calf viability, placental weight and
      placental expulsion.
AB  - A total of 54 Holstein-Friesian cows (13 primiparous and 41 multiparous) was used
      to study maternal plasma oestrone sulphate (E1S) during pregnancy and its
      relationship to birth weight and viability of calves and time required for
      placental expulsion after calving. Plasma samples were obtained from the tail
      vein of cows once every month from days 90 to 180, every 2 weeks from days 181 to
      270, and every day from day 270 of gestation to parturition. The E1S
      concentrations were measured by radioimmunoassay, and birth weight, placental
      measurements, neonatal viability and the period from calving to placental
      expulsion were recorded. E1S concentrations were correlated positively (0.71 > or
      = r > or = 0.32, P < 0.05 or P < 0.01) with calf birth weight and weights of
      cotyledons, intercotyledonary membranes and total placenta from days 210 of
      gestation to 1 day prepartum. Calf birth weight was correlated positively (p <
      0.01) with the weight of the cotyledons (r = 0.87), intercotyledonary membranes
      (r = 0.78) and total placenta (r = 0.88). In addition, E1S concentrations were
      positively correlated (0.63 > or = r > or = 0.28, P < 0.05 or P < 0.01) with the
      neonatal viability after day 195 of pregnancy, and were negatively correlated (
      0.29 > or = r > or = -0.55, P < 0.05 or P < 0.01) with the intervals from
      parturition to placental expulsion after 225 days of pregnancy. The results
      suggest that variation among dams for circulating E1S levels during late
      pregnancy may be caused by variation of placental development and ability for
      oestrogen production and conjugation, and they may influence fetal growth,
      neonatal viability and retained placenta.

PMID- 10066105
TI  - Suppression of ovarian activity in the gilt and reversal by exogenous
      gonadotrophin administration.
AB  - The aim of the current experiment was to study the regulation of follicle
      development in the pig using a potent GnRH agonist (GnRH-A) to initially suppress
      follicle development. Large-White hybrid gilts (n = 8) were treated during the
      luteal phase with GnRH-A. Four of these GnRH-A treated gilts and four control
      gilts were given a GnRH bolus on days 14 and 28 after GnRH-A administration or
      during the luteal phase in control gilts. Blood samples were collected for 10 h
      for FSH and LH, after which 1500 IU PMSG were administered and the ovaries and
      uteri recovered 72 h later. A further four GnRH-A treated gilts and four control
      gilts were slaughtered either 28 days after GnRH-A administration or during the
      luteal phase respectively, and all follicles > or = 1 mm diameter were dissected.
      The mean basal plasma FSH level was lower (P < 0.01) in GnRH-A treated than
      control gilts and showed no response to the GnRH challenge although levels
      increased (P < 0.01) in control gilts. The mean basal plasma LH levels were
      similar (P > 0.1) in GnRH-A treated and control gilts. Whilst in GnRH-A treated
      gilts plasma LH levels showed no response to the GnRH challenge, plasma LH levels
      were increased (P < 0.01) in control gilts. Pulsatile LH secretion was abolished
      in GnRH-A treated but not in control gilts. Plasma oestradiol levels were lower
      (P < 0.001) in GnRH-A treated gilts than in control gilts, but nevertheless both
      GnRH-A treated and control gilts responded to PMSG with increased plasma
      oestradiol levels. Treatment with GnRH-A reduced both the mean (2.1 vs. 2.7 mm; P
      < 0.01) and the maximal follicle diameter (4 vs. 6 mm) and reduced (P < 0.01) the
      total number of follicles > or = 2 mm diameter compared with control gilts.
      Administration of PMSG increased both mean follicle diameter (5.1 vs. 4.4 mm; P <
      0.01) and maximal follicle diameter (7 vs. 9 mm) and caused a reduction (P <
      0.001) in the total number of follicles > or = 2 mm diameter in both GnRH-A
      treated and control gilts. In summary, this study has demonstrated, for the first
      time in the pig, that the inhibition of follicle development as a result of
      pituitary down regulation/desensitisation can be reversed by exogenous
      gonadotrophin treatment. This model will be a powerful tool with which to
      investigate the precise regulation of follicle development in the pig.

PMID- 10066106
TI  - Peritoneal fluid from rabbits or goats as media for in vitro maturation,
      fertilization and initial culture of caprine oocytes.
AB  - The efficacy of peritoneal fluid from rabbit and goat for in vitro maturation,
      fertilization and initial culture of embryos from caprine oocytes was evaluated.
      Peritoneal fluid was collected from adult female goats (n = 9) or rabbits (n =
      9). Good quality oocytes were subjected to in vitro maturation and fertilization
      in three different media viz. Tissue Culture Medium (TCM-199), goat Peritoneal
      Fluid (gPF) and rabbit Peritoneal fluid (rPF). Maturation rates were 74.7+/-2.07%
      and 63.6+/-5.28% in TCM-199, gPF 65.8+/-2.54% and 55.6+/-3.79%, and rPF 57.7+/
      1.78% and 44.6+/-3.01% when evaluated on the basis of cumulus cell expansion and
      the achievement of metaphase-II stage, respectively. However, no significant
      differences were observed in respect of maturation rate between the control and
      gPF and between gPF and rPF groups. Freshly ejaculated buck semen was treated
      with heparin (10 microg/ml) and after 45 min incubation with heparin, 8.0% sperm
      were live and acrosome reacted. The proportions of fertilized oocytes based on
      male and female pronuclei formation or on cleavage development were 50.5+/-5.03,
      42.3+/-3.15 and 34.2+/-1.98%; 31.0+/-2.80, 27.9+/-2.12 and 21.8+/-1.69% for TCM,
      gPF and rPF, respectively. It was concluded that peritoneal fluids either from
      goats or rabbits could be used as an alternative medium to TCM-199. However,
      further research is required to confirm its efficacy for embryo development up to
      the blastocyst stage.

PMID- 10066107
TI  - Biological activity of the seminal plasma of alpacas: stimulus for the production
      of LH by pituitary cells.
AB  - South American camelids are induced ovulators and require a stimulus to trigger
      the LH surge responsible for the ovulation. Seminal plasma (SP) of fertile
      alpacas (Lama pacos) was tested using a bioassay of pituitary cells to study the
      effect of seminal plasma on LH release. Plates containing rat pituitary cells (2
      x 10(5) cells/90-95% viability) were cultured adding: (A) whole SP (WSP) treated
      with charcoal-dextran, or 1:2 or 1:4 proportions diluted in culture medium
      (DMEM/HEPES + antibiotics), or (B) 1:2 SP + anti-GnRH rabbit serum (inhibitory
      potency 10(-5) M), or (C) 1:2 SP + anti-GnRH + 100 nM synthetic GnRH (buserelin
      acetate) or (D) 100 nM, 50 nM, 10 nM, and 1 nM synthetic GnRH. Concentration
      (ng/ml) of LH secreted (Sec) and contained (Con) was analyzed using RIA 125I and
      the percentage of Sec and Con in each experiment was determined. The results of
      LH Sec for the cells treated with 50, 10, and 1 nM GnRH were 39, 13, and 1.5%,
      respectively (r2 = 98.41%, r = 0.9920) but cells treated with 100 nM GnRH
      secreted 10% of LH. With WSP, 1:2, or 1:4 SP the LH Sec was of 44.5% (3.25
      ng/ml), 27% (1.9 ng/ml), and 18% (1.2 ng/ml), respectively. The exposure of cells
      to 1:2 SP + anti-GnRH, or to 1:2 SP + anti-GnRH/100 nM GnRH produced 31% (2.20
      ng/ml) and 30% (1.8 ng/ml) of LH Sec, respectively. These results suggest that
      the SP of alpacas could have some factor(s) different from GnRH that would
      contribute to the mechanisms of LH secretion and to the induced ovulation in the
      female alpaca.

PMID- 10066108
TI  - Perspectives on craniofacial syndromes.
AB  - This article reviews syndrome classification; types of anomalies and their
      interrelations; syndrome delineation; birth prevalence; nomenclature; molecular
      delineation; and phenotype/genotype correlations.

PMID- 10066109
TI  - The genetic basis of normal and abnormal craniofacial development.
AB  - In recent years our knowledge of the genetic mechanisms behind animal development
      has increased exponentially, and it has become apparent that these mechanisms
      have been conserved to an astonishing extent during evolution. In this review
      some important groups of developmental regulatory genes are introduced, and their
      roles are discussed in the context of craniofacial morphogenesis. Transcription
      factors regulating both the identity and patterning of embryonic structures and
      the development of individual organs are often called master regulatory genes.
      These genes, as well as other transcription factors, are parts of signaling
      networks mediating cellular communication, including inductive interactions
      between nearby tissues. Experimental studies, in particular the genetic analysis
      of mouse development, continue to demonstrate important roles for increasing
      numbers of these developmental regulatory molecules, including the actual
      signals, their receptors, and transcription factors in the development of the
      jaws, cranial bones, and teeth. Molecular genetic studies have shown that
      mutations in the genes of the signaling networks cause a variety of human
      craniofacial defects.

PMID- 10066110
TI  - Prenatal traces of aberrant neurofacial growth.
AB  - The interrelation between the development of the brain/peripheral nerves and that
      of the surrounding bone tissue is termed neuro-osteology. In orthodontic and
      pediatric practice the development of the hard tissues is evaluated
      radiographically, but the development of the neural tissue within the bone tissue
      is not evaluated. In this review the emphasis is placed on two neuro-osteologic
      interrelations that can be observed on profile radiographs and orthopantomograms,
      respectively. One is the connection between the pituitary gland of the central
      nervous system and the sella turcica (profile radiograph), and the other is the
      association between the peripheral nerves and the development of the dentition
      (orthopantomogram). Pituitary gland/sella turcica: The correlation between
      prenatal malformation in the pituitary gland/sella turcica and the postnatal
      morphology of the sella turcica in holoprosencephaly, spina
      bifida/myelomeningocele, and cri-du-chat syndrome is demonstrated. Peripheral
      nerves/dentition: The prenatal innervation of the dentition is presented.
      Agenesis and tooth malformation occur in constant patterns within the dental arch
      fields that share the same innervation. The findings demonstrate that in
      postnatal diagnosis of the cranium and the teeth, traces of prenatal aberrations
      can be found that are important for neurofacial growth.

PMID- 10066111
TI  - Mandibular malformations: growth characteristics and management in hemifacial
      microsomia and Nager syndrome.
AB  - This review article describes normal and abnormal development of the mandible.
      The focus is on the characteristics of the mandible and its attached muscles in
      the various types of hemifacial microsomia and in Nager syndrome. Management
      protocols for these two types of malformations are presented in relation to
      development stages.

PMID- 10066112
TI  - Is craniofacial morphology in Apert and Crouzon syndromes the same?
AB  - This article reviews previous research on the craniofacial development in Apert
      and Crouzon syndromes and adds new roentgencephalometric information. It is
      concluded that craniofacial development in the two syndromes is not the same.
      Marked differences were found in the calvaria, cranial base, orbit, maxilla,
      zygoma, incisal occlusion, and soft tissue profile. In general, abnormal
      craniofacial morphology was more severe in Apert syndrome than in Crouzon
      syndrome.

PMID- 10066113
TI  - Normal and increased functional asymmetries in the craniofacial area.
AB  - Normal asymmetry in the area of the craniofacial skeleton can be directional or
      fluctuating in nature. Directionality can in principle be found in three
      dimensions: anteroposterior, cranio-caudal, and asymmetries in the left-right
      dimension. When it comes to directional left right differences, an explanation
      has been difficult to find, although expressions of this type are obvious. Recent
      findings made in molecular genetics strongly support the genetic inheritance
      pattern of laterality. When functionally increased asymmetries of facial
      structures are concerned, it is often difficult to determine the exact
      contribution of each factor involved. In the light of recent experimental data,
      however, it seems that the influence of occlusion on the development of balanced
      facial structures is highly important during the early periods of life. A review
      of these factors is given in this article.

PMID- 10066114
TI  - Growth sites and growth mechanisms at risk in cleft lip and palate.
AB  - A newborn with some kind of facial cleft displays certain characteristics of the
      nose, upper lip, and jaw caused by abnormal influence on specific growth sites
      and growth mechanisms. Treatment, particularly surgery, attempts to counteract
      this aberrant development, for both functional and aesthetic reasons. However,
      not infrequently, therapy impedes future midfacial growth to a greater or lesser
      degree. To better understand the varying growth influence, this article aims to
      review certain aspects of growth of the middle third of the face in both normal
      and cleft subjects. The normal elongation of the maxilla, to give space for the
      molars, is usually not affected by lip surgery but rather by scar tissue from
      palatal repair. The displacement of the upper jaw in relation to the vomer is
      recognized. Early surgery should therefore avoid affecting the growth of the
      vomero-(pre)maxillary suture if possible. Periosteal growth, necessary for the
      development of dentoalveolar structures, might be affected by scar tissue from
      palatal repair. Different ways to reduce the development of palatal scars and
      their negative effects on growth are discussed.

PMID- 10066115
TI  - Facial growth after different methods of surgical intervention in patients with
      cleft lip and palate.
AB  - Studies of the influence of surgery on facial growth in cleft lip and palate must
      take into account inherent variations in craniofacial form independent of
      surgery. Primary surgery, the most important iatrogenic influence on facial form,
      can differ in technique, timing, and sequence, and one of the major challenges in
      researching the topic is the remarkably varied clinical protocols in current use.
      Unfortunately, systematic attempts to compare dentofacial outcomes reported in
      the literature are unlikely to be reliable, as methodologic biases cannot be
      overcome. Rigorous intercenter studies can improve the dependability of data and
      provide evidence of the success of cleft services as a whole, but they are still
      subject to biases introduced by differences in surgical skills and underlying
      craniofacial form. These shortcomings are finally being overcome through
      multicenter randomized control trials.

PMID- 10066116
TI  - Genetic craniofacial aberrations.
AB  - Many craniofacial and dental anomalies have a genetic background. Much research
      related to the molecular pathology of genetic conditions is being carried out,
      and new information related to mapping of disease genes, gene identification, and
      mutations in these genes is accumulating with incredible speed. It is important
      to be well informed of the molecular background of the conditions that we treat
      at anomaly clinics. This article reviews the most recent molecular findings
      related to Turner syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome,
      Treacher Collins syndrome, cleidocranial dysplasia, and cleft lip and palate.

PMID- 10066117
TI  - Craniofacial growth in juvenile chronic arthritis.
AB  - The craniofacial growth in children with juvenile chronic arthritis (JCA),
      especially that of the mandible, and the degree of destruction of the mandibular
      condyles vary depending on the heterogeneity in duration and intensity of the
      disease. In JCA children showing destruction of the temporomandibular joint, the
      dentofacial morphology is characterized by overall smaller dimensions of the
      mandible, mandibular retrognathia, a steep mandibular plane, Class II
      malocclusion, dental crowding, and frontal open bite. In children with unilateral
      condylar destruction, asymmetries will develop, with the chin deviating to the
      affected side. The facial morphology of JCA children with condylar lesions
      becomes more abnormal during growth, reflecting a decelerated mandibular
      development and a backward-rotating growth pattern. The main single cause of the
      deviating craniofacial growth is mandibular condylar destruction. Other factors
      that may influence the craniofacial growth are head posture, soft tissue
      stretching, disease activity and drug therapy, type of onset of the disease,
      muscle weakness, decreased functional ability, and orthodontic treatment.

PMID- 10066118
TI  - Clinical aspects of orthodontic treatment for children with juvenile chronic
      arthritis.
AB  - Growth abnormalities as a consequence of temporomandibular joint arthritis in
      children with juvenile chronic arthritis are difficult and complicated problems
      to treat. The diagnosis of the inflammatory condition in the joint is difficult
      but important to the success of the interceptive treatment. The diagnostic
      problems, treatment objectives, and treatment suggestions are discussed in this
      article.

PMID- 10066119
TI  - The effects of myotonic dystrophy and Duchenne muscular dystrophy on the
      orofacial muscles and dentofacial morphology.
AB  - This article takes a closer view of two of the less rare myopathies, myotonic
      dystrophy (MyD) and Duchenne muscular dystrophy (DMD). A high prevalence of
      malocclusions was found among the patients affected by these diseases. The
      development of the malocclusions in MyD patients seems to be strongly related to
      the vertical aberration of their craniofacial growth due to the involvement of
      the masticator, muscles in association with the possibly less affected suprahyoid
      musculature. Thus, a new situation is established around the teeth transversely.
      The lowered tongue is not in a position to counterbalance the forces developed
      during the lowering of the mandible by the stretched facial musculature. This may
      affect the teeth transversely, decreasing the width of the palate and causing
      posterior crossbite. The lowered position of the mandible, in combination with
      the decreased biting forces, may permit an overeruption of the posterior teeth,
      with increased palatal vault height and development of anterior open bite. The
      development of the malocclusions in DMD patients also seems to be strongly
      related to the involvement of the orofacial muscles by the disease. However, the
      posterior crossbite is not developed owing to the narrow maxillary arch, as is
      the case in MyD patients. On the contrary, the posterior crossbite in DMD is due
      to the transversal expansion of the mandibular arch, possibly because of the
      decreased tonus of the masseter muscle near the molars, in combination with the
      enlarged hypotonic tongue and the predominance of the less affected orbicularis
      oris muscle.

PMID- 10066120
TI  - Early developmental traits in class II malocclusion.
AB  - The occlusal traits of Class II occlusion in the deciduous dentition include
      distal terminal plane of the second deciduous molars, distal canine relation,
      large overjet, and large overbite. Other findings are narrow upper dental arch
      and maxillary base and poor anterior spacing. Skeletally, Class II children
      differ less from normal children. The cranial base, including the base flexure,
      and the maxilla are normal. The mandibular corpus and lower facial height are
      short, the gonial angle is large, and the dentoalveolar position of the mandible
      is retruded. The height of the ramus is normal, as is the skeletal position of
      the mandible, with the exception of the chin, which becomes slightly retruded
      after 5 years of age. As most skeletal traits of Class II occlusion develop later
      than the occlusal characteristics, it is suggested that no evidence can be found
      for a skeletal Class II growth pattern in the deciduous dentition. The deficient
      transversal growth of the maxilla and the sagittal growth of the mandible seem to
      cause the typical Class II occlusion. Further skeletal changes are likely to
      develop as secondary adaptations.

PMID- 10066121
TI  - Craniofacial growth in children treated for malignant diseases.
AB  - With the improving cure rate in childhood malignancies, increasing interest has
      been focused on the long-term survivors of childhood cancer and the quality of
      their life. The severity of long-term disturbances in dental and craniofacial
      development is dependent on the age of the child at diagnosis, if chemotherapy is
      combined with radiation or not. With regard to craniofacial development
      combination chemotherapy has no effects compared with healthy controls, whereas
      children treated cranial irradiation before 5 years of age exhibit a reduced
      growth of the mandible. Conditioning before bone marrow transplantation with
      total body irradiation results in a significantly reduced growth of the
      craniofacial skeleton. The mandible was four times more radiosensitive compared
      with the maxilla. With attention to the dental and craniofacial development,
      occlusion and craniomandibular function, children in risk groups should be
      followed, and given prophylactic treatment and intervention at appropriate times
      to reduce the consequences of the disease itself and the therapy given.

PMID- 10066122
TI  - Postural disorders and dentofacial morphology.
AB  - Although the history of opinions regarding poor posture as an etiologic factor
      for deviant dentofacial development and malocclusions is old, very few controlled
      studies on this topic have been done. Most of the articles are anecdotal or
      describe subjective clinical impressions. Some studies do present valid material,
      but unfortunately they often do not provide enough information about the methods
      for postural recording. Based on selected studies, this review concludes that
      there is plausible evidence for an increased prevalence of Angle Class II
      malocclusions associated with hyperlordosis of the cervical spine and an
      increased risk of lateral crossbite in children affected by scoliosis and
      torticollis. Also, documentation of associations between anterior crowding and
      head posture seem convincing.

PMID- 10066124
TI  - Kinetics of interferon-gamma production and its comparison with anti
      listeriolysin O detection in experimental bovine listeriosis.
AB  - The kinetics of the production of interferon gamma (IFN-gamma) in whole blood
      culture and its comparison with anti-listeriolysin O (ALLO) detection by ELISA
      were studied during oral infection of calves with Listeria monocytogenes. Culture
      filtrate antigen (CFA), listeriolysin O (LLO), and sonicated antigen (SA) were
      used to prime the peripheral blood mononuclear cells (PBMCs) and the plasma from
      orally infected calves. IFN-gamma and ALLO appeared as early as day 7 of an oral
      infection. IFN-gamma was detected earlier with LLO than with SA. The Max50
      interleukin (IL-2) activity and IFN-gamma estimated in the culture supernatant
      from PBMCs primed in vitro with different antigens of L. monocytogenes revealed
      high induction of IL-2 and IFN-gamma by CFA, LLO and live antigen. IFN-gamma
      assay and ALLO detection were used for testing cases of repeat breeding in dairy
      cattle. It appeared that detection of IFN-gamma employing LLO can be used to
      diagnose listerial infections.

PMID- 10066125
TI  - Reduced activity of lecithin:cholesterol acyltransferase in the serum of cows
      with ketosis and left displacement of the abomasum.
AB  - Lecithin:cholesterol acyltransferase (LCAT) activity was evaluated in sera from
      cows with ketosis and in some with left displacement of the abomasum (LDA) that
      occurred during early lactation. The enzyme activities of 652 +/- 214 U (mean +/-
      SD) in cows with ketosis (n = 6) and 683 +/- 110 U in those with LDA (n = 5) were
      significantly (p < 0.01) decreased compared to those in healthy normal cows (994
      +/- 65 U, n = 8). Serum concentrations of free cholesterol, cholesteryl esters
      (CE) and phospholipids were similarly decreased in the two diseases. Cows whose
      LCAT activity and CE concentration were lower than the normal values were
      detected while in the non-lactating stage, and some of these cows had ketosis
      after parturition. It is suggested that evaluation of the LCAT activity and of
      the CE concentration during the non-lactating stage would be useful in detecting
      cows that are susceptible to postparturient disorders such as ketosis.

PMID- 10066126
TI  - Age-dependent immunolocalization of fibronectin and histological changes in the
      thymus of rats.
AB  - Age-dependent variations in the immunolocalization of fibronectin (FN) in the
      thymus were investigated in 1-, 6-, 12- and 20-month-old male and female Swiss
      albino rats (Rattus rattus) at the light-microscopic level and the changes with
      ageing in the histological structure of the thymus were also studied. There were
      no significant differences in the age-dependent variations in the
      immunolocalization of fibronectin or in the histological structure of the thymus
      between male and female rats of the same age but there were increases with ageing
      in the fibronectin content of the thymic capsule, the connective tissue between
      the lobules, around blood vessels, and in the medulla and cortex of thymus. The
      connective-tissue content between lobules, fat cells, Hassall's corpuscles, the
      thickness of capsule and the ratio of the medulla to the cortex of the lobules
      showed age-dependent increases in the thymus of rats of both sexes. Decreases in
      the organ weight/body weight ratio were also observed with ageing.

PMID- 10066127
TI  - Some pharmacokinetic parameters and dosage regimens for a long-acting formulation
      of oxytetracycline in 6- to 8-month-old male calves.
AB  - A two-way crossover study was conducted in crossbred male calves (6-8 months old)
      to determine the bioavailability, pharmacokinetics and dosage regimens for a long
      acting formulation of oxytetracycline (OTC-LA). The half-lives of oxytetracycline
      after intravenous and intramuscular administration were 7.8 h and 24 h,
      respectively. The volume of distribution and total body clearance values of the
      drug were 0.86+/-0.07 L and 76.1+/-3.3 (ml/h)/kg, respectively. The maximum
      concentration of the drug in the serum (4.7-7.4 microg/ml) was achieved 8-10 h
      after intramuscular administration. The minimum therapeutic serum concentration
      of drug of > or = 0.5 microg/ml was maintained between 15 min and 84 h after
      intramuscular administration. The intramuscular bioavailability of the drug was
      89.1+/-4.2%. The dosage regimens to maintain the minimum therapeutic serum
      concentrations of OTC following intramuscular administration of OTC-LA were
      computed.

PMID- 10066128
TI  - Comparative disposition kinetics of albendazole in sheep following oral and
      intraruminal administration.
AB  - The pharmacokinetics of albendazole was studied in sheep following single oral
      and intraruminal administration at nematocidal dose rates. The disposition curves
      of its metabolites indicated increased uptake of the drug in sheep following
      intraruminal as compared to oral dosing (p < 0.05). The increased bioavailability
      of benzimidazole anthelmintics given by the intraruminal route could be exploited
      for optimizing the use of anthelmintic for sustained parasite control in small
      ruminants.

PMID- 10066129
TI  - The use of two immunosuppressive drugs, cyclosporin A and tacrolimus, to inhibit
      virus replication and apoptosis in cells infected with feline immunodeficiency
      virus.
AB  - An in vitro model of acute and chronic infections with feline immunodeficiency
      virus (FIV) was used to examine the effect of two immunosuppressive agents,
      cyclosporin A (CsA) and tacrolimus (also known as FK506), on the inhibition of
      the replication of the virus and of apoptosis. Both drugs significantly
      suppressed virus production in a dose-dependent manner in acutely and chronically
      infected cells. The ability of FK506 to inhibit virus replication was much lower
      than that of CsA, and was accompanied by marked antiproliferative activity.
      Treatment of infected cells with either CsA or FK506 did not affect the rise of
      free intracellular Ca2+ but did protect the cells against apoptosis. Thus, the
      antiviral activity of CsA and FK506 makes these compounds promising candidates
      for the development of drugs suitable for the treatment of AIDS.

PMID- 10066130
TI  - Acid-base regulation and control of ventilation in human pregnancy.
AB  - The purposes of this review were twofold: to apply modern physicochemical
      principles to explain changes in acid-base regulation and the control of
      ventilation in human pregnancy; and to demonstrate the value of pregnancy as a
      model for the study of endocrine effects on physiological control systems.
      Application of P.A. Stewart's approach (P.A. Stewart. Can. J. Physiol. Pharmacol.
      61: 1444-1461, 1983) shows that lower values of plasma hydrogen ion concentration
      ([H+]) observed at rest and in association with exercise in pregnancy are the
      result of lower values for carbon dioxide tension (Pco2) and total weak acid
      ([A(tot)]). This effect is partly offset by a lower strong ion difference
      ([SID]). The ability to predict plasma [H+] at rest and following strenuous
      exercise in pregnancy (J.G. Kemp, F.A. Greer, and L.A. Wolfe. J. Appl. Physiol.
      83: 644-651, 1997) supports the validity of Stewart's approach. Jennings and
      associates (D.B. Jennings. Can. J. Physiol. Pharmacol. 72: 1499-1512, 1994) have
      further demonstrated in animal models the involvement of plasma osmolality and
      circulating levels of angiotensin II (ANG II) and arginine vasopressin (AVP) in
      the chemical control of ventilation. We hypothesize that pregnancy-induced
      increases in respiratory sensitivity to carbon dioxide are the combined result of
      reduced plasma osmolality, reduced cerebrospinal fluid [SID], and augmented
      circulating levels of progesterone, ANG II, and AVP.

PMID- 10066131
TI  - Cold exposure and immune function.
AB  - The influence of cold exposure on immune function is reviewed. Data obtained
      mainly on small mammals suggest that the acute effect of severe chilling is a
      suppression of several cellular and humoral components of the immune response,
      including a decrease of lymphocyte proliferation, a down-regulation of the immune
      cascade, a reduction of natural killer (NK) cell count, cytolytic activity,
      activation of complement, and the induction of heat shock proteins. However,
      adaptation to a given cold stimulus appears to develop over the course of 2-3
      weeks. Further work is needed to examine interactions between cold exposure and
      exercise, and to determine whether the disturbances of immune response are
      sufficient to impair immunosurveillance in human subjects.

PMID- 10066132
TI  - Alterations of KCl- and ATP-induced increase in [Ca2+]i in cardiomyocytes from
      vitamin B6 deficient rats.
AB  - Although vitamin B6 deficiency is related to coronary heart disease, no
      information regarding changes in myocardium due to vitamin B6 deficiency is
      available in the literature. In view of the critical role played by Ca2+ in
      cellular function, we investigated alterations in [Ca2+]i induced by KCI or ATP
      in vitamin B6 deficient and age-matched control rats. [Ca2+]i was measured in
      isolated cardiomyocytes by using the Fura-2 fluorescence technique. The KC1
      induced increase in [Ca2+]i was augmented in vitamin B6 deficient cardiomyocytes,
      whereas the ATP-induced increase in [Ca2+]i was attenuated. The specific ATP
      binding to sarcolemma from hearts of vitamin B6 deficient rats was decreased. A
      single injection of vitamin B6 (10 mg/kg) to vitamin B6 deficient animals
      completely reversed the KC1- or ATP-induced changes in [Ca2+]i in cardiomyocytes
      as well as ATP binding with sarcolemma. These results regarding altered
      regulation of [Ca2+]i in cardiomyocytes and sarcolemmal ATP receptors indicate
      myocardial abnormalities due to vitamin B6 deficiency.

PMID- 10066133
TI  - The effect of estradiol on output of adrenocorticotropin and prolactin by fetal
      sheep anterior pituitary cells.
AB  - We examined the hypothesis that estradiol (E2) would affect fetal anterior
      pituitary corticotroph and lactotroph function in vitro, and that any effects
      would be influenced by gestational age. Anterior pituitary cells from fetal sheep
      at day 129 (n = 4) and at day 139 (n = 5) of gestation were cultured. After 96 h
      in culture, cells were treated for 18 h with E2 concentrations ranging from 0 to
      1000 nM, in the presence or absence of 100 nM of corticotropin-releasing hormone
      (CRH), cortisol, arginine vasopressin (AVP), or CRH and cortisol, to examine
      their effects on corticotroph function. Cells were also treated with
      bromocriptine or increasing concentrations of E2 to study their effects on
      lactotroph function. Immunoreactive (ir) adrenocorticotropin (ACTH) and prolactin
      in the culture medium were measured by radioimmunoassay. Levels of cellular pro
      opiomelanocortin (POMC) mRNA and prolactin mRNA were determined by in situ
      hybridization. Immunohistochemistry was used to determine the percentage of cells
      that were immunopositive for ACTH (corticotrophs) or prolactin (lactotrophs).
      ACTH output was stimulated by CRH treatment at day 139 but not at day 129 of
      gestation, and cortisol attenuated this response. ACTH output by cells cultured
      with 10 nM E2 and 100 nM CRH, at 139 days of gestation, was greater than with CRH
      alone (p < 0.05). E2 did not affect basal ACTH output or ACTH output with any
      other treatment or levels of POMC mRNA. Prolactin output was not affected by E2
      treatment. Bromocriptine significantly decreased prolactin output but not levels
      of prolactin mRNA. We conclude that E2 may affect CRH-stimulated fetal sheep
      pituitary corticotroph function late in gestation, but only within a narrow,
      physiological range of concentration.

PMID- 10066134
TI  - The fate of nitrogen from 15N-labeled nitrate after single intravenous
      administration of Na15NO3 in sheep.
AB  - The metabolic fate of nitrogen from 15N-labeled sodium nitrate has been
      investigated in four healthy Polish Merino ewes. 15N-labeled sodium nitrate was
      administered intravenously at the dosage of 400 micromol.kg(-1) body weight.
      Blood plasma and urine concentrations of nitrate, ammonia, and urea and 15N
      enrichment of ammonia and urea were estimated over a 50-h period following 15N
      nitrate administration. Nitrate (NO3-) was slowly eliminated from the blood
      plasma, and the presence of NO3(-) in the blood plasma above the nitrate
      "background" was observed for 50 h. 15N enrichment of blood plasma urea already
      appeared at 15 min and reached the maximum 6 h after 15N-nitrate administration.
      The urinary excretion of nitrate occured during 50 h after 15N-nitrate injection;
      the total urine excretion of NO3(-) was 23.63+/-2.39% of the administered dose.
      The mean urinary recoveries of nitrogen as 15N-urea and 15N-ammonia were 14.76+/
      1.32% and 0.096+/-0.015% of the administered 15N-nitrate dose, respectively. It
      should be pointed out that in total only 38.49% of the administered nitrate-N was
      excreted in urine (as nitrate, ammonia and urea nitrogen) during 50 h. The
      results obtained indicate that sheep are able to store nitrate nitrogen in their
      body. The fate of the remaining approximately 60% of the 15NO3(-) administered
      dose is unknown. The results obtained do not allow one to conclude what fraction
      of the unrecovered approximately 60% of the 15NO3(-) dose was utilized by
      gastrointestinal microorganisms, and (or) metabolized, or stored in sheep
      tissues.

PMID- 10066135
TI  - Prostaglandin E2 inhibition of fetal breathing movements is not sustained during
      prolonged reduced uterine blood flow in sheep.
AB  - Fetal breathing movements (FBM) are inhibited by both exogenous prostaglandin E2
      (PGE2) and ethanol in sheep. Maternal ethanol exposure in late-gestation sheep
      also increases fetal [PGE2]. However, during prolonged reduced uterine blood flow
      (RUBF) when [PGE2] in fetal plasma is already elevated, FBM are not inhibited by
      ethanol. These experiments were designed, therefore, to test the hypothesis that
      the FBM response to PGE2 is also diminished during RUBF. PGE2 (594+/-19 ng.min(
      1).kg(-1) fetal body weight) was infused for 6 h into the jugular vein of RUBF
      (PO2 = 14+/-1 mmHg (1 mmHg = 133.3 Pa); n = 7) and control (PO2 = 22+/-1 mmHg (p
      < 0.01); n = 7) ovine fetuses, and the effect on FBM, electrocortical (ECoG), and
      electroocular activities was determined. The infusion of PGE2 increased plasma
      [PGE2] from 881+/-162 to 1189+/-114 pg.mL(-1) in RUBF fetuses and from 334+/-72
      to 616+/-118 pg.mL(-1) (p < 0.05) in control fetuses. FBM were initially
      inhibited by PGE2 from 22.5+/-9.4 and 17.9+/-6.5% of the time to 6.9+/-2.4 and
      0.5+/-0.4% (p < 0.01) in RUBF and control fetuses, respectively. FBM remained
      inhibited in control fetuses throughout the infusion but returned to baseline
      incidence in RUBF fetuses in the last 2 h of the infusion. These results are
      consistent with the hypothesis that one component of the adaptative mechanisms of
      the fetus to prolonged RUBF is an altered response of FBM to exogenous PGE2. We
      speculate that the lack of a sustained inhibition in FBM during RUBF with
      infusion of PGE2 may be a result of an alteration in brainstem receptor function
      or number or local PGE2 removal.

PMID- 10066136
TI  - Stimulation and inhibition of resting muscle thermogenesis by vasoconstrictors in
      perfused rat hind limb.
AB  - Angiotensin (AII) and serotonin (5-HT) are both vasoconstrictors of the constant
      flow perfused rat hind limb that have opposite effects on thermogenesis, possibly
      the result of differing effects on vascular flow distribution between nutritive
      and non-nutritive pathways. In the present study interaction between the two
      opposing agents was examined with the expectation that the combined presence
      would show additive effects on pressure and mutually neutralizing effects on
      thermogenesis. Thus doses of AII and 5-HT that gave similar, but opposite,
      quantitative effects on thermogenesis were infused alone, in combination one
      after the other, or in combination with the order reversed, and the effects on
      perfusion pressure (PP) and thermogenesis (oxygen uptake, VO2) were compared. AII
      (3 nM) alone increased PP by 15+/-1 mmHg (1 mmHg = 133.3 Pa) and VO2 by 3.1-/+0.2
      micromol.h(-1).g(-1), whereas 5-HT (1 microM) alone increased PP by 75+/-6 mmHg
      and inhibited VO2 by 3.9+/-0.2 micromol.h(-1).g(-1). When added in combination,
      the outcome depended on the order of addition. Following AII, infusion of 5-HT
      further increased PP by 160+/-11 mmHg and decreased VO2 by 6.3+/-0.2 micromol.h(
      1)g(-1). Following 5-HT, infusion of AII further increased PP by 28+/-4 mmHg and
      increased VO2 by only 1.8+/-0.3 micromol.h(-1).g(-1). The prior presence of 5-HT
      (1 microM) shifted the AII dose-response curves for VO2 and pressure to the right
      and left, respectively. The prior infusion of AII increased the dose-dependent
      response to 5-HT in terms of both the inhibition of VO2 and the increase in PP.
      At low doses of 5-HT (10(-8)-10(-7) M), but not alpha-methyl serotonin (alphaMT),
      there was a marked vasodilatation-associated inhibition of AII-mediated increase
      in VO2. Overall the data show that the combined effect of AII and 5-HT differed
      from the simple addition of each separately. Since the order of addition appears
      to be critical in terms of thermogenic outcome, it is concluded that each
      vasoconstrictor exerts a specific hemodynamic action to affect access of the
      other to vascular receptor sites. These findings are consistent with the
      previously reported effects of these vasoconstrictors on substrate and insulin
      access to muscle of the perfused rat hind limb.

PMID- 10066137
TI  - L-type Ca2+ currents in ventricular myocytes from neonatal and adult rats.
AB  - Postnatal changes in the slow Ca2+ current (I(Ca)(L)) were investigated in
      freshly isolated ventricular myocytes from neonatal (1-7 days old) and adult (2-4
      months old) rats, using whole-cell voltage clamp and single-channel recordings.
      The membrane capacitance (mean+/-SEM) averaged 23.2+/-0.5 pF in neonates (n =
      163) and 140+/-4.1 pF in adults (n = 143). I(Ca)(L) was measured as the peak
      inward current at a test potential of +10 mV (or +20 mV) by applying a 300-ms
      pulse from a holding potential of -40 mV; 1.8 mM Ca2+ was used as charge carrier.
      The basal ICa(L) density was 6.7+/-0.2 pA/pF in neonatal and 7.8+/-0.2 pA/pF in
      adult cells (p < 0.05). The time course of inactivation of the fast component (at
      +10 ms) was significantly longer in the neonatal (10.7+/-1.4 ms) than in the
      adult (6.6+/-0.4 ms) cells (p < 0.05). Ryanodine (10+/-M) significantly increased
      this value to 18.0+/-1.9 in neonate (n = 8) and to 17.7+/-2.0 in adult (n = 9).
      For steady-state inactivation, the half-inactivation potential (Vh) was not
      changed in either group. For steady-state activation, Vh was 5.1 mV in the
      neonatal (n = 6) and -7.9 mV in the adult cells (n = 7). Single-channel
      recordings revealed that long openings (mode-2 behavior) were occasionally
      observed in the neonatal cells (11 events from 1080 traces/11 cells), but not in
      the adult cells (400 traces/4 cells). Slope conductance was 24 pS in both the
      neonatal and adult cells. Results in rat ventricular myocytes suggest the
      following: (i) the peak Ca2+ current density is already well developed in the
      neonatal period (being about 85% of the adult value); (ii) the fast component of
      inactivation is slower in neonates than in adults; and (iii) naturally occurring
      long openings are occasionally observed in the neonatal stage but not in the
      adult. Thus, the L-type Ca2+ channels of the neonate were slightly lower in
      density, were inactivated more slowly, and occasionally exhibited mode-2 behavior
      as compared with those of the adult.

PMID- 10066138
TI  - HCO3-secretion by bullfrog duodenum: dependence on nutrient Na+ during secretory
      stimulation.
AB  - HCO3(-) secretion across in vitro duodenal mucosa of Rana catesbeiana was
      investigated under baseline conditions and during secretory stimulation. Baseline
      secretion was abolished by removal of CO2-HCO3(-)and reduced approximately 60% by
      removal of nutrient Na+, but was not sensitive to changes in Cl- or K+. Baseline
      secretion was not directly altered by exposure to 10(-3) M amiloride or 10(-3) M
      H2DIDS (dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) in the nutrient
      solution and only mildly reduced by acetazolamide. Following removal and
      restoration of Na+, recovery of secretion was impaired by exposure to
      acetazolamide (5 x 10(-4) M) or H2DIDS (5 x 10(-4) M) in the nutrient solution.
      Secretion stimulated by glucagon (10(-6) M) or 16,16-dimethyl prostaglandin E2
      (10 microg.mL(-1)) was markedly attenuated by removal of Na+ or by exposure to
      H2DIDS, but secretion was not altered by acetazolamide (5 x 10(-4) M) or nutrient
      amiloride (1 mM). Thus, the HCO3(-) that is secreted under nonstimulated
      conditions derives partly from basolateral Na(+)-dependent uptake and partly from
      cellular CO2 hydration. Secretagogue-stimulated secretion by duodenal surface
      epithelium depends on stilbene-sensitive Na+(HCO3(-))n uptake across the
      basolateral membrane.

PMID- 10066139
TI  - Higher mitochondrial fatty acid oxidation following intermittent versus
      continuous endurance exercise training.
AB  - It has been well documented that skeletal muscle fatty acid oxidation can be
      elevated by continuous endurance exercise training. However, it remains
      questionable whether similar adaptations can be induced with intermittent
      interval exercise training. This study was undertaken to directly compare the
      rates of fatty acid oxidation in isolated subsarcolemmal (SS) and
      intermyofibrillar (IMF) mitochondria following these different exercise training
      regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of
      male Sprague-Dawley rats following exercise training 6 days per week for 12
      weeks. Exercise training consisted of either continuous, submaximal, endurance
      treadmill running (n = 10) or intermittent, high intensity, interval running (n =
      10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate
      in both mitochondrial populations (p < 0.05). However, the increase associated
      with the intermittent, high intensity exercise training was significantly greater
      than that achieved with the continuous exercise training (p < 0.05). Also, the
      increases associated with the IMF mitochondria were greater than the SS
      mitochondria (p < 0.05). These data suggest that high intensity, intermittent
      interval exercise training is more effective for stimulation of fatty acid
      oxidation than continuous submaximal exercise training and that this adaptation
      occurs preferentially within IMF mitochondria.

PMID- 10066140
TI  - The efficacy of diazepam in the treatment of acute iron overload in rats.
AB  - While conducting studies on the prevention of mortality from acute iron
      intoxication in rats, diazepam, given to prevent animal suffering, was observed
      to be associated with reduced mortality in a limited number of animals. The
      objective was to assess whether diazepam reduces mortality following acute iron
      intoxication in rats. Survival of rats was compared among groups receiving (i)
      orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of
      2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone
      intraperitoneal injections. The administration of DZ decreased mortality from 60
      to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality
      (p < 0.05 compared with the DZ group) over the study period. The administration
      of DZ was not associated with decreased iron absorption or increased urinary iron
      excretion, whereas the administration of deferiprone did result in urinary iron
      excretion. Microscopic examination suggests that diazepam administration may be
      associated with lower intracellular accumulation of iron. In conclusion, diazepam
      reduces mortality from iron overdose in rats through a yet unidentified
      mechanism, although the drug does not inhibit iron absorption or enhance urinary
      iron removal.

PMID- 10066141
TI  - Actions of excitatory amino acids on mesencephalic trigeminal neurons.
AB  - Mesencephalic trigeminal (MeV) neurons are primary sensory neurons of which the
      cell soma is located within the brainstem, and is associated with synaptic
      contacts. In previous studies it has been reported that these cells are resistant
      to kainic acid excitotoxicity, and have little or no responsiveness to
      exogenously applied glutamate or selective agonists. In an in vitro slice
      preparation with intracellular recording, we have found that these cells respond
      to pressure-applied glutamate, N-methyl-D-aspartic acid (NMDA), kainate (KA), and
      (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). The
      kainate and AMPA responses appear to be mediated by different receptors, at least
      in part, since they exhibit differing sensitivity to an AMPA receptor selective
      antagonist. The agonists generally evoke larger responses than glutamate and
      exhibit a long-duration desensitization requiring approximately 10 min for full
      recovery. Some cross-desensitization between the glutamate agonists is also
      observed. Mesencephalic trigeminal neurons exhibit high-frequency oscillatory
      activity during depolarizations that approach threshold potentials, and these
      could combine with transmitter-induced depolarizations to enhance the
      excitability of these cells. Previous reports of nonsensitivity to glutamate and
      to kainate excitotoxicity are attributable to relatively small responses, and to
      the desensitization expressed by these neurons.

PMID- 10066142
TI  - Modulation of GABA(A) receptor function by neuroactive steroids: evidence for
      heterogeneity of steroid sensitivity of recombinant GABA(A) receptor isoforms.
AB  - Neuroactive steroids are potent, selective allosteric modulators of gamma
      aminobutyric acid type A (GABA(A)) receptor function in the central nervous
      system, and may serve as endogenous anxiolytic and analgesic agents. In order to
      study the influence of subunit subtypes of the GABA(A) receptor on modulation of
      receptor function by neuroactive steroids, we expressed human recombinant GABA(A)
      receptors in Xenopus oocytes. GABA-activated membrane current, and the modulatory
      effects of the endogenous neurosteroid 5alpha-pregnan-3alpha-ol-20-one
      (allopregnanolone) and the synthetic steroid anesthetic 5alpha-pregnan-3alpha-ol
      11,20-dione (alphaxalone) were measured using two-electrode voltage-clamp
      recording techniques. Allopregnanolone had similar effects to potentiate GABA
      activated membrane current in the alpha1beta1gamma2L and alpha1beta2gamma2L
      receptor isoforms. In contrast, alphaxalone was much more effective as a positive
      allosteric modulator on the alpha1beta1gamma2L receptor isoform. In the absence
      of the gamma2L subunit subtype, allopregnanolone had much greater efficacy, but
      its potency was decreased. Allopregnanolone was much more effective on the
      alpha1beta1 receptor isoform compared with the alpha1beta2 receptor isoform. The
      potency for alphaxalone to potentiate the GABA response was not altered in the
      absence of the gamma2L subunit subtype, although its efficacy was greatly
      enhanced. Both allopregnanolone and alphaxalone produced nonparallel leftward
      shifts in the GABA concentration-response relationship in the absence of the
      gamma2L subunit, decreasing the EC50 concentration of GABA and increasing the
      maximal response. Only alphaxalone increased the maximal GABA response when the
      gamma2L subunit subtype was present. The 3beta-pregnane isomers epipregnanolone
      and isopregnanolone both inhibited the ability of allopregnanolone and
      alphaxalone to potentiate GABA(A) receptor function. However, the degree of block
      produced by the 3beta-pregnane steroid isomers was dependent on the type of
      receptor isoform studied and the neuroactive steroid tested. Isopregnanolone, the
      3beta-isomer of allopregnanolone, was significantly more effective as a blocker
      of potentiation caused by allopregnanolone compared with alphaxalone in all
      receptor isoforms tested. Epipregnanolone had a greater efficacy as a blocker at
      the alpha1beta2gamma2L receptor isoform compared with the alpha1beta1gamma2L
      receptor isoform, and also produced a greater degree of block of potentiation
      caused by allopregnanolone compared with alphaxalone. Our results support the
      hypothesis that the heteromeric assembly of different GABA(A) receptor isoforms
      containing different subunit subtypes results in multiple steroid recognition
      sites on GABA(A) receptors, which in turn produces distinctly different
      modulatory interactions between neuroactive steroids acting at the GABA(A)
      receptor. The alpha and gamma subunit subtypes may have the greatest influence on
      allopregnanolone modulation of GABA(A) receptor function, whereas the beta and
      gamma subunit subtypes appear to be most important for the modulatory effects of
      alphaxalone.

PMID- 10066143
TI  - The biochemical and pharmacological properties of a newly synthesized H+-K+
      ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2
      a]benzimidazol e.
AB  - This study was designed to determine the effect of a newly synthesized proton
      pump inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]be
      nzimidazole (YJA20379-2), on gastric H(+)-K(+) ATPase activity, acid secretion,
      and experimental gastroduodenal lesions or ulcers in rats. YJA20379-2 inhibited
      in a concentration-dependent manner the proton pump (H(+)-K(+) ATPase) activity
      in isolated hog gastric mucosal microsomes, therefore, confirming its
      classification as a proton pump inhibitor. The inhibitory efficacy of YJA20379-2
      on the proton pump was about eight times higher than that of omeprazole at pH
      7.4. The activity of the inhibited enzyme was not restored by dilution and
      washout method, so this implied that the inhibition of YJA20379-2 is not
      reversible. YJA20379-2, given intraduodenally or orally, potently suppressed acid
      secretion in pylorus-ligated rats, with ED50 values of 3.6 and 7.7 mg.kg(-1),
      respectively. Pretreatment with YJA20379-2 dose dependently protected the gastric
      mucosa from damage induced by absolute ethanol, water-immersion stress,
      indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats,
      with ED50 values of 11.0, 21.0, 0.5, and 18.7 mg.kg(-1), respectively. Repeated
      administration of YJA20379-2 also dose dependently accelerated spontaneous
      healing of acetic acid induced gastric ulcers. These results suggest that
      YJA20379-2 has potent antisecretory and antiulcer effects, which are exerted by
      suppression of H(+)-K(+) ATPase activity in gastric parietal cells, such that
      YJA20379-2 may be useful for the clinical treatment of peptic ulcer diseases.

PMID- 10066144
TI  - Intracardiac iron distribution in newborn guinea pigs following isolated and
      combined fetal hypoxemia and fetal iron deficiency.
AB  - Myocardial iron deficiency complicates chronic intrauterine hypoxemia during
      diabetic pregnancies. To understand the effect of both conditions during fetal
      life on intracardiac iron prioritization, we measured heart myoglobin, cytochrome
      c, and elemental iron concentrations in six iron-deficient, hypoxic, five iron
      sufficient, hypoxic, six iron-deficient, normoxic, and six iron-sufficient,
      normoxic newborn guinea pigs. The iron-deficient, hypoxic group had lower heart
      iron (p = 0.03) but higher myoglobin concentration (p < 0.0001) when compared
      with the iron-sufficient, normoxic group. The percentage of iron incorporated
      into myoglobin was higher than control in the iron-deficient, hypoxic group
      (23.2+/-7.2% vs. 5.2+/-0.8%; p < 0.001) and increased as total heart iron
      decreased (r = 0.97; p < 0.001). In contrast, heart cytochrome c concentration
      was lower than control in the iron-deficient, hypoxic group (p = 0.01), with
      equal percentages of heart iron incorporated into cytochrome c. This
      intracellular prioritization of myocardial iron to myoglobin and away from
      cytochrome c following combined fetal hypoxemia and iron deficiency may represent
      an adaptive mechanism to preserve myocardial tissue oxygenation, although at the
      expense of oxidative phosphorylative capability.

PMID- 10066145
TI  - Platelet function in the newborn.
AB  - Whole blood flow cytometry, an important new method for the assessment of
      platelet function, is particularly advantageous for neonatal studies because only
      minuscule volumes (approximately 2 microL) of blood are required. By this method,
      we have demonstrated that neonatal platelets are less reactive than adult
      platelets to physiological agonists in whole blood, as determined by the
      activation-induced increase in the platelet surface expression of P-selectin and
      the glycoprotein (GP) IIb-IIIa complex and by the activation-induced decrease in
      the platelet surface expression of the GPIb-IX complex. Our data suggest that the
      mechanism of neonatal platelet hyporeactivity is, at least in part, a relative
      defect in a common signal transduction pathway. We have further demonstrated that
      the platelets of very low birth weight (VLBW) preterm neonates are maximally
      hyporeactive on days 3 to 4 of life but return to almost the adult range by days
      10 to 14. Given that intraventricular hemorrhage (IVH) is also maximal on days 3
      to 4, these defects may contribute to the propensity of VLBW preterm neonates to
      IVH.

PMID- 10066146
TI  - Platelet function tests in childhood. Measuring aggregation and release reaction
      in whole blood.
AB  - Blood samples from 42 newborns, 78 infants and schoolchildren, and 81 healthy
      adults were tested for the parameters of primary hemostasis. Only whole blood
      techniques were used. Agonist-induced aggregation and release-reaction studies
      were performed in a whole blood lumi-aggregometer simultaneously. The release of
      adenosine triphosphate (ATP) was detected by the luciferin-luciferase method. The
      in vitro bleeding time was measured by the PFA 100 system. The results of these
      studies were ostensibly influenced by blood cells. Many aggregation phenomena
      were correlated with the platelet count. Aggregation and release reaction by
      collagen were inversely correlated with the hematocrit. In the PFA 100,
      hematocrit and leukocyte count were also inversely correlated with the closure
      time and the maximal blood flow velocity. Both parameters were diminished in
      newborns. The aggregation response to adenosine diphosphate (ADP) was similar in
      the three groups. The same was true for the aggregation and release reaction by
      arachidonic acid and for the agglutination by ristocetin. The aggregation and
      release reaction by collagen were diminished in the specimens from newborns. For
      the explanation of this transient hypofunction, only theoretical considerations
      exist. Beyond the postnatal period and during childhood, no remarkable
      differences from the adult norm were found.

PMID- 10066147
TI  - Use of the PFA-100 in the assessment of primary, platelet-related hemostasis in a
      pediatric setting.
AB  - The platelet function analyzer, PFA-100, has been designed to provide an in vitro
      measure of primary hemostasis simply, quickly, quantitatively, and accurately to
      aid in the routine screening of patients with potential hemorrhagic risk due to
      abnormal platelet plug formation. The system measures the closure time (CT), or
      the time taken for platelets in a sample of anticoagulated blood to form a plug
      that occludes a microscopic aperture cut into a membrane coated with collagen and
      either epinephrine or ADP. The high shear stresses produced in the analyzer lead
      to platelet plug formation that is greatly dependent on von Willebrand's factor
      (vWF). In this article, we detail the system itself and describe our initial
      studies using the PFA-100 to assess primary hemostasis in pediatric populations.
      Normal ranges have been established for healthy children and neonates. CTs for
      healthy children are independent of the needle gauge (21G or 23G) used for blood
      sampling. They are similar to CTs for healthy adults, but neonates have
      significantly shorter CTs, likely due to increased levels of vWF. Children with
      hemophilia have normal CTs, whereas seven out of eight patients with von
      Willebrand's disease (vWD) have abnormally long CTs. CT reproducibility between
      duplicate samples is excellent. Our preliminary results indicate that the PFA-100
      will be useful in the evaluation of primary hemostasis in children, as well as in
      adults.

PMID- 10066148
TI  - The bleeding time in pediatrics.
AB  - When performed with standardized methods and techniques, the bleeding time (BT)
      depends on variables that physiologically alter primary hemostasis. These
      variables include number of platelets and platelet function, white and red blood
      cell counts, vascular factors, hormones, and temperature. Variations within
      normal limits reflect the in vivo situation and are of no clinical relevance. If
      the BT is prolonged far above the upper normal limit, however, defects of primary
      hemostasis have to be anticipated. These include thrombocytopenia or
      thrombocytopathy, anemia, leukopenia, and deficiencies of plasmatic factors such
      as von Willebrand factor (vWF), fibrinogen, the lupus anticoagulant, and factor
      V. The BT can be used as screening test for patients with bleeding symptoms. As a
      single test, the BT gives the best information in pediatrics, in which defects of
      primary hemostasis are more common than coagulopathies. In addition, BT can guide
      the therapy of these patients, because it reflects clinical improvement. When
      used as a preoperative screening test, BT should be combined with the activated
      partial thromboplastin time (aPTT) because BT usually does not recognize patients
      with coagulopathies. With standardized techniques and the knowledge of its merits
      and limitations, BT is a useful test for diagnosing hemostatic disorders, guiding
      their therapy, and warning of unexpected bleeding complications during surgery.
      The BT is especially suited for use in pediatrics for the following reasons: (1)
      It does not require a venipuncture and is similar to capillary blood sampling if
      performed with standardized devices adapted for pediatric use; (2) it is an in
      vivo test informing mostly on defects of primary hemostasis, which are the most
      common bleeding diatheses in childhood; (3) the results are immediately
      available; (4) it requires only minimal amounts of blood; and (5) it does not
      require unphysiological reagents and preparation of the sample. The test requires
      a highly motivated and experienced operator who knows of the many variables
      influencing the BT. The interpretation cannot be done without knowledge of the
      history and physical status of the patient and of the limitations of the BT.

PMID- 10066149
TI  - Acute immune thrombocytopenia in childhood. Are we treating the platelet count?
AB  - Acute immune thrombocytopenia (ITP) in children is a benign disease, presenting
      mostly with skin purpura and minor bleeds. It has a high rate of spontaneous
      remission. Intracranial hemorrhage (ICH) is extremely rare; the risk is higher
      during the chronic phase and in children with additional risk factors. The
      threshold platelet count in ITP is not known because of problems with platelet
      counting in thrombocytopenia and the lack of clinical data. The threshold is
      probably lower than in leukemia, because primary hemostasis is better in ITP. So
      far, there is no proof for the clinical efficacy of treatment or prophylaxis with
      intravenous immunoglobulin (IVIg) and glucocorticoids (GC), medications that have
      several adverse effects. The question remains open whether or not we are treating
      the platelet count in children with acute ITP.

PMID- 10066150
TI  - Chronic immune thrombocytopenic purpura in childhood.
AB  - Immune thrombocytopenic purpura (ITP) is a bleeding disorder and is traditionally
      divided in acute and chronic forms based on the duration of the disease. Chronic
      ITP is characterized by a persistence of thrombocytopenia for more than 6 months.
      Ten to 20% of children with ITP and almost all adults will develop the chronic
      condition. Pathophysiology of chronic ITP suggests an autoimmune process and a
      dysregulated immune response. There are no risk factors to predict the clinical
      course of ITP. Controlled clinical trials are needed to clarify many diagnostic
      and therapeutic aspects of chronic ITP, as recently stated by a panel of
      pediatric and adult hematologists on behalf of The American Society of Hematology
      (ASH). In this article, we will focus on pathophysiological, diagnostic, and
      management aspects of chronic childhood ITP.

PMID- 10066151
TI  - Desmopressin (DDAVP) in bleeding disorders of childhood.
AB  - As in adults, desmopressin (DDAVP) can be used in children for prophylaxis of
      bleeding and to stop bleeding in many hereditary and acquired bleeding disorders.
      DDAVP is the treatment of choice in children with mild hemophilia and type 1 von
      Willebrand's disease (vWD). It is effective in some variants of vWD and in many
      patients with platelet function defects. It reduces the bleeding diathesis of
      children with uremia and drug-induced bleeding complications. In any case, a test
      dose of DDAVP has to be given to the patient to predict the hemostatic effect
      before relying on this drug for treatment. The response can be measured by
      shortening of the bleeding time (BT) and of partial thromboplastin time (PTT),
      indicating a rise of Factor (F) VIII or von Willebrand factor (vWF). Side effects
      such as facial flushing, transient headache, increased pulse rate, and drop in
      systolic blood pressure are mild and transient. They can be minimized when the
      dose is not exceeding 0.3 microg/kg body weight, and the infusion lasts at least
      20 to 30 minutes. The strong antidiuretic action of DDAVP has some potential
      problems that are negligible in adults and older children when water intake is
      restricted. In infants and small children under the age of 18 months, however,
      DDAVP should be used with caution and with close surveillance in order to prevent
      water intoxication and electrolyte imbalance. The danger is increased when the
      patients receive parenteral fluid substitution. The advantages of DDAVP include
      the reduction in the use of plasma factor concentrates, thereby minimizing the
      danger of immunological or infectious complications, as well as the considerable
      reduction of costs realized by treatment with this form of medication.
      Fortunately, it can be applied successfully in the most frequent hereditary
      bleeding disorder, namely vWD type 1.

PMID- 10066152
TI  - The rational use of platelet transfusions in children.
AB  - Platelet transfusions are undoubtedly effective in securing hemostasis in
      bleeding children with absent or nonfunctioning platelets. They are, however,
      abused in some circumstances and are not without risk. The use of platelet
      transfusions to prevent rather than to treat bleeding in children with malignant
      disease has increased several times over the last two decades. When joining in
      this widespread practice, physicians should be aware that there is a relatively
      unimpressive evidence base supporting it and also that for patients with
      uncomplicated myelo-suppression the most persuasive studies suggest that a
      threshold platelet count of 10 x 10(9)/L is no less effective than the more
      customary 20 x 10(9)/L is. Still lower thresholds await evaluation. For children
      with nonmalignant conditions the use of platelet transfusions should be carefully
      evaluated on a case-by-case basis, but they should normally be avoided in the
      absence of clinically important bleeding. Neonates with thrombocytopenia,
      particularly those with immune disease due to a maternal alloantibody, are
      considered an exception to this generalization. The serious hazards of platelet
      transfusions include alloimmunization and the induction of refractoriness, graft
      versus-host (GVH) disease, and the transmission of infection, all of which can be
      life threatening. Less risky alternative therapeutic approaches may become more
      widely available in the future, including recombinant thrombopoietin and
      lyophilized heat-treated platelet membrane preparations.

PMID- 10066153
TI  - Coagulation changes associated with the hemolytic uremic syndrome.
AB  - The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, acute
      renal failure, and thrombocytopenia. The pathological correlate is thrombotic
      microangiopathy of glomerular capillaries and arterioles in the kidneys and
      almost every other organ. The presence of platelet thrombi without extensive
      soluble coagulation system activation is a constant feature of HUS and thrombotic
      thrombocytopenic purpura (TTP). Damage to the endothelial cell seems to be a
      central event in the pathogenesis of HUS and TTP, resulting in loss of
      fibrinolytic properties and subsequent thrombotic occlusion of the
      microvasculature. According to earlier and recent studies, a variety of
      hemostatic alterations have been described. Among the many findings, low platelet
      counts, increased von Willebrand's factor (vWF), and normal fibrinogen are almost
      invariably observed. The dubious long-term outcome, even of postdiarrheal HUS,
      which is believed to have a more favorable prognosis than HUS of other
      etiopathogenic origin, necessitates further investigation of the pathophysiology
      of thrombotic microangiopathy and meticulous reevaluation of treatment strategies
      aimed at interfering with the process of thrombosis early in the disease course.
      The intention of this article is to highlight findings possibly relevant for
      disease management and to give an overview of the putative pathomechanisms
      involved.

PMID- 10066154
TI  - Vascular hemostasis in flowing blood in children.
AB  - This review considers differences in hemostasis among newborns, children, and
      adults from the standpoint of the vascular endothelium and, where appropriate, in
      the presence of flowing blood. Special procoagulant features of newborn
      hemostasis include unusually large von Willebrand factor multimers, augmented
      platelet transport under flow conditions, and greater ability of newborn
      endothelium to generate tissue factor. Special anticoagulant features in the
      newborn include increased vessel wall glycosaminoglycan activity, elevated alpha2
      macroglobulin, and increased percentage of free protein S. The net effect of the
      differences is that hemostasis is generally achieved in all age groups but is
      developmental in nature. In addition to congenital hypercoagulable states and
      catheter placement, developmental vascular anomalies appear to constitute a
      thrombotic risk, at least in some children (and possibly adults).

PMID- 10066155
TI  - Antiphospholipid antibodies in children.
AB  - Lupus anticoagulant (LA) is made up of heterogeneous IgG and IgM antibodies that
      prolong clotting times in vitro and is associated with an increased rate of both
      thrombosis and hemorrhage in vivo, although thrombosis is far more common. Many
      mechanisms of action have been explored, but none explains the coagulation
      abnormality of every sample tested. Binding of these antibodies to protein
      phospholipid complexes provides a unifying model. Antiphospholipid antibodies
      (APAs) are found in adult patients with a variety of disorders or as an isolated
      finding. The association of LA and anticardiolipin antibodies (ACAs) with
      thrombosis in adults has been established, although there is no test as yet to
      predict thrombotic risk for an asymptomatic affected individual. The presentation
      of thrombosis with postinfectious APA is uncommon in adults. Children who present
      with thrombosis and LA are found to have underlying disorders similar to those of
      adults. Although the presentation of thrombosis in children with postinfectious
      LA is rare, the association is established. LA-positive children with thrombosis
      have manifested a severe acquired deficiency of protein S; LA-positive children
      with hemorrhage have manifested an acquired deficiency of prothrombin. The
      association of thrombosis with ACA-positive children has been reported. Further
      work to determine the epidemiology, mechanism of action, and thrombotic potential
      of APA in children is warranted to better understand, prevent, and treat
      thrombotic and hemorrhagic complications.

PMID- 10066156
TI  - Whole blood clot lysis in newborns and adults after adding different
      concentrations of recombinant tissue plasminogen activator (Rt-PA).
AB  - Optimal treatment of newborns with thromboembolic complications likely differs
      from that for adults because of ontogenetic features of both coagulation and
      fibrinolysis that affect the thrombotic processes and the response to
      thrombolytic agents. Although there are data on plasma clot lysis in newborns,
      the potential for dissolution of whole blood clots has not been explored. We
      investigated whether there is a difference between newborns and adults in
      sensitivity of whole blood clots to lysis with recombinant tissue plasminogen
      activator (rt-PA). Blood was obtained from 15 newborns and from 13 adults and
      anticoagulated with sodium citrate. Whole blood clots were generated by addition
      of thrombin and calcium. After 3 hours of retraction the clots were put into
      tubes containing 1.45 mL plasma of the same patient. After 1 hour of incubation,
      rt-PA was added to result in final concentrations of 3, 1, 0.3, 0.1, and 0
      microg/mL. Clots were weighed after 0.5, 1, 2, and 3 hours. At any time point
      measured, whole blood clot lysis was more efficient in newborns than it was in
      adults. This was true for spontaneous clot lysis (p <0.05 at 1, 2, and 3 hours)
      as well as for all concentrations of rt-PA tested (p <0.05 at 1 hour). Whole
      blood clot lysis in new-borns was most efficient at 1 microg/mL rt-PA, whereas
      adults showed best lysis at the highest concentration tested (3 microg/mL rt-PA).
      The rate of plasminogen consumption was similar in newborns and adults.
      Recommendations for antithrombotic therapy in new-borns have been loosely
      extrapolated from recommendations for adults. Our data can be helpful in
      establishing guidelines for thrombolytic therapy in the neonatal period.
      Retracted whole blood clots mimic better the in vivo situation than previously
      reported in studies of lysis of nonretracted plasma clots. Based on our data, we
      think that despite low levels and slower activation kinetics of fetal
      plasminogen, the dosage of rt-PA should be lower in newborns than in adults.

PMID- 10066157
TI  - Polymorphonuclear elastase in patients with homozygous type I plasminogen
      deficiency and ligneous conjunctivitis.
AB  - Laboratory studies were performed on six female patients (ranging in age from 1
      to 31 years) with ligneous conjunctivitis, which we regard as a systemic
      condition consisting of ligneous conjunctivitis and other pseudomembranous
      lesions. Plasminogen levels were severely reduced in all six patients; five
      patients were homozygous, and one patient was double heterozygous for type I
      plasminogen deficiency. Of family members tested, 11 of 12 parents and two of six
      siblings tested were diagnosed as heterozygous. No thrombotic episodes had
      occurred in any of the patients. Polymorphonuclear (PMN) elastase protein levels
      were markedly elevated in all, significantly more so in the homozygous patients
      (range 88 to 335 ng/mL; normal range, 20+/-10 ng/mL) than in the heterozygous
      patient (58 ng/mL). Of 11 parents examined, only 1 mother had normal PMN elastase
      (27 ng/mL, with plasminogen antigen 60% and plasminogen functional activity 86%),
      whereas values were moderately elevated (range 42 to 110 ng/mL) in the other 10
      parents examined. After plasminogen substitution, PMN elastase levels
      consistently decreased but did not reach normal values. We interpret our findings
      as indicating that non-plasmin-induced fibrinolytic processes, possibly mediated
      via elastase, may be intensified in patients with plasminogen deficiency.

PMID- 10066158
TI  - Snake venom hemorrhagins.
AB  - Viperine and crotaline snake venoms contain one or more hemorrhagic principles
      called hemorrhagins. These are zinc-containing metalloproteases characterized by
      the presence of a protease domain, with additional domains in some of them. They
      act essentially by degrading the component proteins of basement membrane
      underlying capillary endothelial cells. The toxins also act on these cells
      causing lysis or drifting apart, resulting in hemorrhage per rhexis or per
      diapedesis. Some of these toxins have been found to exert additional effects such
      as fibrinogenolysis and platelet aggregation that facilitate hemorrhage. The
      structural and functional features of this class of toxins have been discussed in
      this review in an attempt to get a better understanding of their toxicity. This
      can be of immense therapeutic value in the management of snake venom poisoning,
      as hemorrhagins are among the major lethal factors in snake venom.

PMID- 10066159
TI  - The role of phosphotriesterases in the detoxication of organophosphorus
      compounds.
AB  - The enzymes that hydrolyze organophosphorus compounds are called
      phosphotriesterases. The presence of phosphotriesterases has been described in a
      variety of tissues. The physiological role of these enzymes is not known,
      although a clear correlation exists between the levels of phosphotriesterases and
      susceptibility of the species to the toxic effects of organophosphorus compounds.
      Thus, mammals that possess high levels of phosphotriesterases in serum and liver
      are more tolerant to the toxic effects of these compounds than birds and insects 
      these being species considered lacking of phosphotriesterases. Because most of
      these enzymes are not well characterized, they are usually differentiated
      according to their different patterns of response to activators and/ or
      inhibitors. Phosphotriesterases usually depend of divalent cations and therefore
      EDTA usually inhibits them. A peculiar EDTA-resistant phosphotriesterase has been
      described in serum albumin. The biotechnological and therapeutical applications
      of phosphotriesterases are currently subject to study.

PMID- 10066160
TI  - Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione
      S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism
      and toxicity.
AB  - In this review, an overview is presented of the current knowledge of genetic
      polymorphisms of four of the most important enzyme families involved in the
      metabolism of xenobiotics, that is, the N-acetyltransferase (NAT), cytochrome
      P450 (P450), glutathione-S-transferase (GST), and microsomal epoxide hydrolase
      (mEH) enzymes. The emphasis is on two main topics, the molecular genetics of the
      polymorphisms and the consequences for xenobiotic metabolism and toxicity.
      Studies are described in which wild-type and mutant alleles of biotransformation
      enzymes have been expressed in heterologous systems to study the molecular
      genetics and the metabolism and pharmacological or toxicological effects of
      xenobiotics. Furthermore, studies are described that have investigated the
      effects of genetic polymorphisms of biotransformation enzymes on the metabolism
      of drugs in humans and on the metabolism of genotoxic compounds in vivo as well.
      The effects of the polymorphisms are highly dependent on the enzyme systems
      involved and the compounds being metabolized. Several polymorphisms are described
      that also clearly influence the metabolism and effects of drugs and toxic
      compounds, in vivo in humans. Future perspectives in studies on genetic
      polymorphisms of biotransformation enzymes are also discussed. It is concluded
      that genetic polymorphisms of biotransformation enzymes are in a number of cases
      a major factor involved in the interindividual variability in xenobiotic
      metabolism and toxicity. This may lead to interindividual variability in efficacy
      of drugs and disease susceptibility.

PMID- 10066161
TI  - Mitochondrial evolution.
AB  - The serial endosymbiosis theory is a favored model for explaining the origin of
      mitochondria, a defining event in the evolution of eukaryotic cells. As usually
      described, this theory posits that mitochondria are the direct descendants of a
      bacterial endosymbiont that became established at an early stage in a nucleus
      containing (but amitochondriate) host cell. Gene sequence data strongly support a
      monophyletic origin of the mitochondrion from a eubacterial ancestor shared with
      a subgroup of the alpha-Proteobacteria. However, recent studies of unicellular
      eukaryotes (protists), some of them little known, have provided insights that
      challenge the traditional serial endosymbiosis-based view of how the eukaryotic
      cell and its mitochondrion came to be. These data indicate that the mitochondrion
      arose in a common ancestor of all extant eukaryotes and raise the possibility
      that this organelle originated at essentially the same time as the nuclear
      component of the eukaryotic cell rather than in a separate, subsequent event.

PMID- 10066162
TI  - Mitochondrial diseases in man and mouse.
AB  - Over the past 10 years, mitochondrial defects have been implicated in a wide
      variety of degenerative diseases, aging, and cancer. Studies on patients with
      these diseases have revealed much about the complexities of mitochondrial
      genetics, which involves an interplay between mutations in the mitochondrial and
      nuclear genomes. However, the pathophysiology of mitochondrial diseases has
      remained perplexing. The essential role of mitochondrial oxidative
      phosphorylation in cellular energy production, the generation of reactive oxygen
      species, and the initiation of apoptosis has suggested a number of novel
      mechanisms for mitochondrial pathology. The importance and interrelationship of
      these functions are now being studied in mouse models of mitochondrial disease.

PMID- 10066163
TI  - Oxidative phosphorylation at the fin de siecle.
AB  - Mitochondria produce most of the energy in animal cells by a process called
      oxidative phosphorylation. Electrons are passed along a series of respiratory
      enzyme complexes located in the inner mitochondrial membrane, and the energy
      released by this electron transfer is used to pump protons across the membrane.
      The resultant electrochemical gradient enables another complex, adenosine 5'
      triphosphate (ATP) synthase, to synthesize the energy carrier ATP. Important new
      mechanistic insights into oxidative phosphorylation have emerged from recent
      three-dimensional structural analyses of ATP synthase and two of the respiratory
      enzyme complexes, cytochrome bc1 and cytochrome c oxidase. This work, and new
      enzymological studies of ATP synthase's unusual catalytic mechanism, are reviewed
      here.

PMID- 10066164
TI  - The machinery of mitochondrial inheritance and behavior.
AB  - The distribution of mitochondria to daughter cells during cell division is an
      essential feature of cell proliferation. Until recently, it was commonly believed
      that inheritance of mitochondria and other organelles was a passive process, a
      consequence of their random diffusion throughout the cytoplasm. A growing
      recognition of the reticular morphology of mitochondria in many living cells, the
      association of mitochondria with the cytoskeleton, and the coordinated movements
      of mitochondria during cellular division and differentiation has illuminated the
      necessity for a cellular machinery that mediates mitochondrial behavior.
      Characterization of the underlying molecular components of this machinery is
      providing insight into mechanisms regulating mitochondrial morphology and
      distribution.

PMID- 10066166
TI  - Controlling the morphology of amorphous solid water 
AB  - The morphology of amorphous solid water grown by vapor deposition was found to
      depend strongly on the angular distribution of the water molecules incident from
      the gas phase. Systematic variation of the incident angle during deposition using
      a collimated beam of water led to the growth of nonporous to highly porous
      amorphous solid water. The physical and chemical properties of amorphous solid
      water are of interest because of its presence in astrophysical environments. The
      ability to control its properties in the laboratory may shed light on some of the
      outstanding conflicts related to this important material.

PMID- 10066165
TI  - A glycyl radical site in the crystal structure of a class III ribonucleotide
      reductase.
AB  - Ribonucleotide reductases catalyze the reduction of ribonucleotides to
      deoxyribonucleotides. Three classes have been identified, all using free-radical
      chemistry but based on different cofactors. Classes I and II have been shown to
      be evolutionarily related, whereas the origin of anaerobic class III has remained
      elusive. The structure of a class III enzyme suggests a common origin for the
      three classes but shows differences in the active site that can be understood on
      the basis of the radical-initiation system and source of reductive electrons, as
      well as a unique protein glycyl radical site. A possible evolutionary
      relationship between early deoxyribonucleotide metabolism and primary anaerobic
      metabolism is suggested.

PMID- 10066167
TI  - Semimajor axis mobility of asteroidal fragments 
AB  - The semimajor axes of asteroids up to about 20 kilometers in diameter drift as a
      result of the Yarkovsky effect, a subtle nongravitational mechanism related to
      radiation pressure recoil on spinning objects that orbit the sun. Over the
      collisional lifetimes of these objects (typically, 10 to 1000 million years),
      orbital semimajor axes can be moved by a few hundredths of an astronomical unit
      for bodies between 1 and 10 kilometers in mean radius. This has implications for
      the delivery of multikilometer near-Earth asteroids, because the Yarkovsky drift
      drives many small main-belt asteroids into the resonances that transport them to
      the Mars-crossing state and eventually to near-Earth space. Recent work has shown
      that, without such a drift, the Mars-crossing population would be depleted over
      about 100 million years, a time scale much smaller than the age of the solar
      system. Moreover, the Yarkovsky semimajor axis mobility may spread in an
      observable way the tight semimajor axis clustering of small asteroids produced as
      a consequence of disruptive collisions.

PMID- 10066168
TI  - Quartzlike carbon dioxide: An optically nonlinear extended solid at high
      pressures and temperatures 
AB  - An extended-solid phase, carbon dioxide phase V (CO2-V), was synthesized in a
      diamond anvil cell by laser heating the molecular orthorhombic phase, carbon
      dioxide phase III, above 40 gigapascals and 1800 kelvin. This new material can be
      quenched to ambient temperature above 1 gigapascal. The vibration spectrum of CO2
      V is similar to that of the quartz polymorph of silicon dioxide, indicating that
      it is an extended covalent solid with carbon-oxygen single bonds. This material
      is also optically nonlinear, generating the second harmonic of a neodymium
      yttrium-lithium-fluoride laser at a wavelength of 527 nanometers with a
      conversion efficiency that is near 0.1 percent.

PMID- 10066169
TI  - Electrostatic deflections and electromechanical resonances of carbon nanotubes 
AB  - Static and dynamic mechanical deflections were electrically induced in
      cantilevered, multiwalled carbon nanotubes in a transmission electron microscope.
      The nanotubes were resonantly excited at the fundamental frequency and higher
      harmonics as revealed by their deflected contours, which correspond closely to
      those determined for cantilevered elastic beams. The elastic bending modulus as a
      function of diameter was found to decrease sharply (from about 1 to 0.1
      terapascals) with increasing diameter (from 8 to 40 nanometers), which indicates
      a crossover from a uniform elastic mode to an elastic mode that involves wavelike
      distortions in the nanotube. The quality factors of the resonances are on the
      order of 500. The methods developed here have been applied to a nanobalance for
      nanoscopic particles and also to a Kelvin probe based on nanotubes.

PMID- 10066170
TI  - An elusive blind-thrust fault beneath metropolitan los angeles 
AB  - Seismic reflection profiles, petroleum wells, and relocated earthquakes reveal
      the presence of an active blind-thrust fault beneath metropolitan Los Angeles. A
      segment of this fault likely caused the 1987 Whittier Narrows (magnitude 6.0)
      earthquake. Mapped sizes of other fault segments suggest that the system is
      capable of much larger (magnitude 6.5 to 7) and more destructive earthquakes.

PMID- 10066171
TI  - Evolution of the continents and the atmosphere inferred from Th-U-Nb systematics
      of the depleted mantle 
AB  - Temporal evolution of depleted mantle thorium-uranium-niobium systematics
      constrain the amount of continental crust present through Earth's history
      (through the niobium/thorium ratio) and date formation of a globally oxidizing
      atmosphere and hydrosphere at approximately 2.0 billion years ago (through the
      niobium/uranium ratio). Increase in the niobium/thorium ratio shows involvement
      of hydrated lithosphere in differentiation of Earth since approximately 3.8
      billion years ago. After approximately 2.0 billion years ago, the decreasing
      mantle thorium/uranium ratio portrays mainly preferential recycling of uranium in
      an oxidizing atmosphere and hydrosphere. Net growth rate of continental crust has
      varied over time, and continents are still growing today.

PMID- 10066172
TI  - Rapid thinning of parts of the southern greenland ice sheet 
AB  - Aircraft laser-altimeter surveys over southern Greenland in 1993 and 1998 show
      three areas of thickening by more than 10 centimeters per year in the southern
      part of the region and large areas of thinning, particularly in the east. Above
      2000 meters elevation the ice sheet is in balance but thinning predominates at
      lower elevations, with rates exceeding 1 meter per year on east coast outlet
      glaciers. These high thinning rates occur at different latitudes and at
      elevations up to 1500 meters, which suggests that they are caused by increased
      rates of creep thinning rather than by excessive melting. Taken as a whole, the
      surveyed region is in negative balance.

PMID- 10066173
TI  - A functional model for O-O bond formation by the O2-evolving complex in
      photosystem II.
AB  - The formation of molecular oxygen from water in photosynthesis is catalyzed by
      photosystem II at an active site containing four manganese ions that are arranged
      in di-mu-oxo dimanganese units (where mu is a bridging mode). The complex
      [H2O(terpy)Mn(O)2Mn(terpy)OH2](NO3)3 (terpy is 2,2':6', 2"-terpyridine), which
      was synthesized and structurally characterized, contains a di-mu-oxo manganese
      dimer and catalyzes the conversion of sodium hypochlorite to molecular oxygen.
      Oxygen-18 isotope labeling showed that water is the source of the oxygen atoms in
      the molecular oxygen evolved, and so this system is a functional model for
      photosynthetic water oxidation.

PMID- 10066174
TI  - Episodic fluctuations in larval supply 
AB  - The lack of a clear relationship between spawning output and recruitment success
      continues to confound attempts to understand and manage temporally variable fish
      populations. This relationship for a common reef fish is shown to be obscured by
      nonlinear processes in operation during the larval phase. Nonlinear responses of
      larval fish to their noisy physical environment may offer a general explanation
      for the erratic, often episodic, replenishment of open marine populations.

PMID- 10066175
TI  - Exon shuffling by L1 retrotransposition.
AB  - Long interspersed nuclear elements (LINE-1s or L1s) are the most abundant
      retrotransposons in the human genome, and they serve as major sources of reverse
      transcriptase activity. Engineered L1s retrotranspose at high frequency in
      cultured human cells. Here it is shown that L1s insert into transcribed genes and
      retrotranspose sequences derived from their 3' flanks to new genomic locations.
      Thus, retrotransposition-competent L1s provide a vehicle to mobilize non-L1
      sequences, such as exons or promoters, into existing genes and may represent a
      general mechanism for the evolution of new genes.

PMID- 10066176
TI  - Adhesive and mammalian transglutaminase substrate properties of Candida albicans
      Hwp1.
AB  - The pathogenesis of candidiasis involves invasion of host tissues by filamentous
      forms of the opportunistic yeast Candida albicans. Morphology-specific gene
      products may confer proinvasive properties. A hypha-specific surface protein,
      Hwp1, with similarities to mammalian small proline-rich proteins was shown to
      serve as a substrate for mammalian transglutaminases. Candida albicans strains
      lacking Hwp1 were unable to form stable attachments to human buccal epithelial
      cells and had a reduced capacity to cause systemic candidiasis in mice. This
      represents a paradigm for microbial adhesion that implicates essential host
      enzymes.

PMID- 10066177
TI  - The predictive value of changes in effective connectivity for human learning.
AB  - During learning, neural responses decrease over repeated exposure to identical
      stimuli. This repetition suppression is thought to reflect a progressive
      optimization of neuronal responses elicited by the task. Functional magnetic
      resonance imaging was used to study the neural basis of associative learning of
      visual objects and their locations. As expected, activation in specialized
      cortical areas decreased with time. However, with path analysis it was shown
      that, in parallel to this adaptation, increases in effective connectivity
      occurred between distinct cortical systems specialized for spatial and object
      processing. The time course of these plastic changes was highly correlated with
      individual learning performance, suggesting that interactions between brain areas
      underlie associative learning.

PMID- 10066178
TI  - Cytokinin activation of Arabidopsis cell division through a D-type cyclin.
AB  - Cytokinins are plant hormones that regulate plant cell division. The D-type
      cyclin CycD3 was found to be elevated in a mutant of Arabidopsis with a high
      level of cytokinin and to be rapidly induced by cytokinin application in both
      cell cultures and whole plants. Constitutive expression of CycD3 in transgenic
      plants allowed induction and maintenance of cell division in the absence of
      exogenous cytokinin. Results suggest that cytokinin activates Arabidopsis cell
      division through induction of CycD3 at the G1-S cell cycle phase transition.

PMID- 10066179
TI  - Increased insulin sensitivity and obesity resistance in mice lacking the protein
      tyrosine phosphatase-1B gene.
AB  - Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative
      regulation of insulin signaling. Disruption of the mouse homolog of the gene
      encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose
      concentrations that were slightly lower and concentrations of circulating insulin
      that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin
      sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin
      tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the
      insulin receptor in liver and muscle tissue after insulin injection in comparison
      to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were
      resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+
      mice rapidly gained weight and became insulin resistant. These results
      demonstrate that PTP-1B has a major role in modulating both insulin sensitivity
      and fuel metabolism, thereby establishing it as a potential therapeutic target in
      the treatment of type 2 diabetes and obesity.

PMID- 10066180
TI  - Acetylcholinesterase inhibitors for Alzheimer's disease.

PMID- 10066181
TI  - Something borrowed from the blues?

PMID- 10066182
TI  - Endoscopic treatment of bile duct stones in elderly people.

PMID- 10066183
TI  - The role of the routine neonatal examination.

PMID- 10066184
TI  - BMJ introduces a fast track system for papers. We will offer to publish
      exceptional papers within four weeks 

PMID- 10066185
TI  - Swedish study questions mammography screening programmes.

PMID- 10066187
TI  - In brief 

PMID- 10066186
TI  - UK introduces "NHS oscars" 

PMID- 10066189
TI  - US launches campaign to combat medicare fraud.

PMID- 10066188
TI  - UK commission recommends new ways to fund care of elderly people 

PMID- 10066190
TI  - Adding chemotherapy improves survival in cervical cancer.

PMID- 10066192
TI  - Hungarian university starts first migration medicine course.

PMID- 10066191
TI  - UK class tobacco action nears collapse.

PMID- 10066193
TI  - Research shows optimal spacing for healthy babies 

PMID- 10066194
TI  - China cracks down on counterfeit medicines.

PMID- 10066196
TI  - Surgery increases risk ofsporadic CJD 

PMID- 10066195
TI  - NHS to come under race relations act.

PMID- 10066197
TI  - Autoimmune reaction links chlamydia to heart disease 

PMID- 10066198
TI  - Vancomycin resistant staphylococcus reported in Hong Kong.

PMID- 10066199
TI  - UK medical schools should expand to meet staff shortages.

PMID- 10066200
TI  - Irish government to set up tribunal for hearing loss in soldiers.

PMID- 10066201
TI  - Neonatal examination and screening trial (NEST): a randomised, controlled,
      switchback trial of alternative policies for low risk infants.
AB  - OBJECTIVE: To evaluate the effectiveness of one rather than two hospital neonatal
      examinations in detection of abnormalities. DESIGN: Randomised controlled
      switchback trial. SETTING: Postnatal wards in a teaching hospital in north east
      Scotland. PARTICIPANTS: All infants delivered at the hospital between March 1993
      and February 1995. INTERVENTION: A policy of one neonatal screening examination
      compared with a policy of two. MAIN OUTCOME MEASURES: Congenital conditions
      diagnosed in hospital; results of community health assessments at 8 weeks and 8
      months; outpatient referrals; inpatient admissions; use of general practioner
      services; focused analysis of outcomes for suspected hip and heart abnormalities.
      RESULTS: 4835 babies were allocated to receive one screening examination (one
      screen policy) and 4877 to receive two (two screen policy). More congenital
      conditions were suspected at discharge among babies examined twice (9.9 v 8.3
      diagnoses per 100 babies; 95% confidence interval for difference 0.3 to 2.7).
      There was no overall significant difference between the groups in use of
      community, outpatient, or inpatient resources or in health care received.
      Although more babies who were examined twice attended orthopaedic outpatient
      clinics (340 (7%) v 289 (6%)), particularly for suspected congenital dislocation
      of the hip (176 (3.6/100 babies) v 137 (2.8/100 babies); difference -0.8; -1.5 to
      0.1), there was no significant difference in the number of babies who required
      active management (12 (0.2%) v 15 (0.3%)). CONCLUSIONS: Despite more suspected
      abnormalities, there was no evidence of net health gain from a policy of two
      hospital neonatal examinations. Adoption of a single examination policy would
      save resources both during the postnatal hospital stay and through fewer
      outpatient consultations.

PMID- 10066202
TI  - Footsteps and faces 

PMID- 10066204
TI  - Rational drug design for Alzheimer's disease 

PMID- 10066203
TI  - Efficacy and safety of rivastigmine in patients with Alzheimer's disease:
      international randomised controlled trial.
AB  - OBJECTIVES: To assess the effects of rivastigmine on the core domains of
      Alzheimer's disease. DESIGN: Prospective, randomised, multicentre, double blind,
      placebo controlled, parallel group trial. Patients received either placebo, 1-4
      mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine.
      Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day)
      over the first 12 weeks with a subsequent assessment period of 14 weeks. SETTING:
      45 centres in Europe and North America. PARTICIPANTS: 725 patients with mild to
      moderately severe probable Alzheimer's disease diagnosed according to the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the
      criteria of the National Institute of Neurological and Communicative Disorders
      and Stroke and the Alzheimer's Disease and Related Disorders Association. OUTCOME
      MEASURES: Cognitive subscale of the Alzheimer's disease assessment scale, rating
      on the clinician interview based impression of change incorporating caregiver
      information scale, and the progressive deterioration scale. RESULTS: At the end
      of the study cognitive function had deteriorated among those in the placebo
      group. Scores on the Alzheimer's disease assessment scale improved in patients in
      the higher dose group when compared with patients taking placebo (P<0.05).
      Significantly more patients in the higher dose group had improved by 4 points or
      more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global
      function as rated by the clinician interview scale had significantly improved
      among those in the higher dose group compared with those taking placebo
      (P<0.001), and significantly more patients in the higher dose group showed
      improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean
      scores on the progressive deterioration scale improved from baseline in patients
      in the higher dose group but fell in the placebo group. Adverse events were
      predominantly gastrointestinal, of mild to moderate severity, transient, and
      occurred mainly during escalation of the dose. 23% (55/242) of those in the
      higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239)
      of those in the placebo group discontinued treatment because of adverse events.
      CONCLUSIONS: Rivastigmine is well tolerated and effective. It improves cognition,
      participation in activities of daily living, and global evaluation ratings in
      patients with mild to moderately severe Alzheimer's disease. This is the first
      treatment to show compelling evidence of efficacy in a predominantly European
      population.

PMID- 10066205
TI  - Patients' and doctors' attitudes to amount of information given after unintended
      injury during treatment: cross sectional, questionnaire survey.

PMID- 10066206
TI  - Cross sectional survey of cervical cancer screening in women with learning
      disability.

PMID- 10066208
TI  - Child labour 

PMID- 10066207
TI  - Socioeconomic differences in childhood consultation rates in general practice in
      England and Wales: prospective cohort study.
AB  - OBJECTIVE: To establish how consultation rates in children for episodes of
      illness, preventive activities, and home visits vary by social class. DESIGN:
      Analysis of prospectively collected data from the fourth national survey of
      morbidity in general practice, carried out between September 1991 and August
      1992. SETTING: 60 general practices in England and Wales. SUBJECTS: 106 102
      children aged 0 to 15 years registered with the participating practices. MAIN
      OUTCOME MEASURES: Mean overall consultation rates for any reason, illness by
      severity of underlying disease, preventive episodes, home visits, and specific
      diagnostic category (infections, asthma, and injuries). RESULTS: Overall
      consultation rates increased from registrar general's social classes I-II to
      classes IV-V in a linear pattern (for IV-V v I-II rate ratio 1.18; 95% confidence
      interval 1.14 to 1. 22). Children from social classes IV-V consulted more
      frequently than children from classes I-II for illnesses (rate ratio 1.23; 1.15
      to 1.30), including infections, asthma, and injuries and poisonings. They also
      had significantly higher consultation rates for minor, moderate, and serious
      illnesses and higher home visiting rates (rate ratio 2.00; 1.81 to 2.18).
      Consultations for preventive activities were lower in children from social
      classes IV-V than in children from social classes I-II (rate ratio 0.95; 0.86 to
      1.05). CONCLUSIONS: Childhood consultation rates for episodes of illness increase
      from social classes I-II through to classes IV-V. The findings on severity of
      underlying illness suggest the health of children from lower social classes is
      worse than that of children from higher social classes. These results reinforce
      the need to identify and target children for preventive health care in their
      socioeconomic context.

PMID- 10066209
TI  - Published criteria for evaluating health related web sites: review.
AB  - OBJECTIVE: To review published criteria for specifically evaluating health
      related information on the world wide web, and to identify areas of consensus.
      DESIGN: Search of world wide web sites and peer reviewed medical journals for
      explicit criteria for evaluating health related information on the web, using
      Medline and Lexis-Nexis databases, and the following internet search engines:
      Yahoo!, Excite, Altavista, Webcrawler, HotBot, Infoseek, Magellan Internet Guide,
      and Lycos. Criteria were extracted and grouped into categories. RESULTS: 29
      published rating tools and journal articles were identified that had explicit
      criteria for assessing health related web sites. Of the 165 criteria extracted
      from these tools and articles, 132 (80%) were grouped under one of 12 specific
      categories and 33 (20%) were grouped as miscellaneous because they lacked
      specificity or were unique. The most frequently cited criteria were those dealing
      with content, design and aesthetics of site, disclosure of authors, sponsors, or
      developers, currency of information (includes frequency of update, freshness,
      maintenance of site), authority of source, ease of use, and accessibility and
      availability. CONCLUSIONS: Results suggest that many authors agree on key
      criteria for evaluating health related web sites, and that efforts to develop
      consensus criteria may be helpful. The next step is to identify and assess a
      clear, simple set of consensus criteria that the general public can understand
      and use.

PMID- 10066210
TI  - How to start 

PMID- 10066211
TI  - Fortnightly review: Intracoronary stents.

PMID- 10066212
TI  - ABC of sexual health. Sexual variations.

PMID- 10066213
TI  - Roles and responsibilities of the problem based learning tutor in the
      undergraduate medical curriculum.

PMID- 10066214
TI  - Medical aid associations 

PMID- 10066215
TI  - Legal and political considerations of clinical practice guidelines.

PMID- 10066216
TI  - Carriage of meningococci in contacts of patients with meningococcal disease.
      "Kissing contacts" need to be defined.

PMID- 10066217
TI  - Primary care arrangements for elderly people in residential and nursing homes.

PMID- 10066218
TI  - Treating type 2 diabetes. Study was conducted in exemplary fashion.

PMID- 10066219
TI  - Long stay care and the NHS. Multidisciplinary assessment is needed.

PMID- 10066220
TI  - Scotland needs a bed inquiry.

PMID- 10066221
TI  - Sildenafil (Viagra) is used as a recreational drug in England.

PMID- 10066222
TI  - Contributors to antibiotic resistance. Antibiotics should not be first treatment
      for acne.

PMID- 10066223
TI  - "Medication concordance" is best helped by improving consultation skills.

PMID- 10066224
TI  - Meeting health needs of asylum seekers. White paper will make access to health
      care more difficult.

PMID- 10066225
TI  - Register cannot replace prospective studies in sickle cell disease.

PMID- 10066227
TI  - Anthony dominic abdullah 

PMID- 10066226
TI  - Helping airline passengers. Guidance on legal position would be helpful.

PMID- 10066228
TI  - GPs will set up an english committee 

PMID- 10066230
TI  - Blood and bone 

PMID- 10066229
TI  - Duchenne and gachet 

PMID- 10066232
TI  - Bookcase 

PMID- 10066231
TI  - Nature medicine 

PMID- 10066234
TI  - Website of the week 

PMID- 10066233
TI  - Down and loud 

PMID- 10066235
TI  - Tackling institutional racism 

PMID- 10066237
TI  - Once is enough for neonatal screening 

PMID- 10066236
TI  - Making them squirm 

PMID- 10066238
TI  - Rivastigmine may improve functioning in mild to moderate Alzheimer's disease 

PMID- 10066239
TI  - Patients want more information than doctors want to give 

PMID- 10066241
TI  - Children from lower social classes consult more often 

PMID- 10066240
TI  - Women with learning disability are not being screened for cervical cancer 

PMID- 10066242
TI  - Consensus on criteria for evaluating health related web sites is emerging 

PMID- 10066243
TI  - Differential distribution of three members of a gene family encoding low voltage
      activated (T-type) calcium channels.
AB  - Low voltage-activated (T-type) calcium currents are observed in many central and
      peripheral neurons and display distinct physiological and functional properties.
      Using in situ hybridization, we have localized central and peripheral nervous
      system expression of three transcripts (alpha1G, alpha1H, and alpha1I) of the T
      type calcium channel family (CaVT). Each mRNA demonstrated a unique distribution,
      and expression of the three genes was largely complementary. We found high levels
      of expression of these transcripts in regions associated with prominent T-type
      currents, including inferior olivary and thalamic relay neurons (which expressed
      alpha1G), sensory ganglia, pituitary, and dentate gyrus granule neurons
      (alpha1H), and thalamic reticular neurons (alpha1I and alpha1H). Other regions of
      high expression included the Purkinje cell layer of the cerebellum, the bed
      nucleus of the stria terminalis, the claustrum (alpha1G), the olfactory tubercles
      (alpha1H and alpha1I), and the subthalamic nucleus (alpha1I and alpha1G). Some
      neurons expressed high levels of all three genes, including hippocampal pyramidal
      neurons and olfactory granule cells. Many brain regions showed a predominance of
      labeling for alpha1G, including the amygdala, cerebral cortex, rostral
      hypothalamus, brainstem, and spinal cord. Exceptions included the basal ganglia,
      which showed more prominent labeling for alpha1H and alpha1I, and the olfactory
      bulb, the hippocampus, and the caudal hypothalamus, which showed more even levels
      of all three transcripts. Our results are consistent with the hypothesis that
      differential gene expression underlies pharmacological and physiological
      heterogeneity observed in neuronal T-type calcium currents, and they provide a
      molecular basis for the study of T-type channels in particular neurons.

PMID- 10066244
TI  - Cloning and expression of a novel member of the low voltage-activated T-type
      calcium channel family.
AB  - Low voltage-activated Ca2+ channels play important roles in pacing neuronal
      firing and producing network oscillations, such as those that occur during sleep
      and epilepsy. Here we describe the cloning and expression of the third member of
      the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated
      that it is predominantly expressed in brain. Expression of the cloned channel in
      either Xenopus oocytes or stably transfected human embryonic kidney-293 cells
      revealed novel gating properties. We compared these electrophysiological
      properties to those of the cloned T-type channels alpha1G and alpha1H and to the
      high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels
      opened after small depolarizations of the membrane similar to alpha1G and alpha1H
      but at more depolarized potentials. The kinetics of activation and inactivation
      were dramatically slower, which allows the channel to act as a Ca2+ injector. In
      oocytes, the kinetics were even slower, suggesting that components of the
      expression system modulate its gating properties. Steady-state inactivation
      occurred at higher potentials than any of the other T channels, endowing the
      channel with a substantial window current. The alpha1I channel could still be
      classified as T-type by virtue of its criss-crossing kinetics, its slow
      deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+
      solutions. Based on its brain distribution and novel gating properties, we
      suggest that alpha1I plays important roles in determining the
      electroresponsiveness of neurons, and hence, may be a novel drug target.

PMID- 10066245
TI  - The synaptophysin-synaptobrevin complex: a hallmark of synaptic vesicle
      maturation.
AB  - Exocytosis of synaptic vesicles requires the formation of a fusion complex
      consisting of the synaptic vesicle protein synaptobrevin (vesicle-associated
      membrane protein, or VAMP) and the plasma membrane proteins syntaxin and soluble
      synaptosomal-associated protein of 25 kDa (or SNAP 25). In search of mechanisms
      that regulate the assembly of the fusion complex, it was found that synaptobrevin
      also binds to the vesicle protein synaptophysin and that synaptophysin-bound
      synaptobrevin cannot enter the fusion complex. Using a combination of
      immunoprecipitation, cross-linking, and in vitro interaction experiments, we
      report here that the synaptophysin-synaptobrevin complex is upregulated during
      neuronal development. In embryonic rat brain, the complex is not detectable,
      although synaptophysin and synaptobrevin are expressed and are localized to the
      same nerve terminals and to the same pool of vesicles. In contrast, the ability
      of synaptobrevin to participate in the fusion complex is detectable as early as
      embryonic day 14. The binding of synaptoporin, a closely related homolog of
      synaptophysin, to synaptobrevin changes in a similar manner during development.
      Recombinant synaptobrevin binds to synaptophysin derived from adult brain
      extracts but not to that derived from embryonic brain extracts. Furthermore, the
      soluble cytosol fraction of adult, but not of embryonic, synaptosomes contains a
      protein that induces synaptophysin-synaptobrevin complex formation in embryonic
      vesicle fractions. We conclude that complex formation is regulated during
      development and is mediated by a posttranslational modification of synaptophysin.
      Furthermore, we propose that the synaptophysin-synaptobrevin complex is not
      essential for exocytosis but rather provides a reserve pool of synaptobrevin for
      exocytosis that can be readily recruited during periods of high synaptic
      activity.

PMID- 10066246
TI  - Temperature-dependent modulation of excitatory transmission in hippocampal slices
      is mediated by extracellular adenosine.
AB  - Although extracellular adenosine concentrations in brain are increased markedly
      by a variety of stimuli such as hypoxia and ischemia, it has been difficult to
      demonstrate large increases in adenosine with stimuli that do not result in
      pathological tissue damage. The present studies demonstrate that increasing the
      temperature at which rat hippocampal brain slices are maintained (typically from
      32.5 to 38.5 degrees C) markedly inhibits excitatory synaptic transmission. This
      effect was reversible on cooling, readily repeatable, and was blocked by A1
      receptor antagonists and by adenosine deaminase, suggesting that it was mediated
      by increased activation of presynaptic adenosine A1 receptors by endogenous
      adenosine. This increase in adenosinergic inhibition was not a response to
      hyperthermia per se, because it could be elicited by temperatures that remained
      entirely within the hypothermic range (e. g., from 32.5 to 35.5 degrees C). The
      increased activity at A1 receptors appeared to be attributable to the direct
      release of adenosine via nucleoside transporters; the release of adenine
      nucleotides, linked to either the activation of NMDA receptors or the increased
      efflux of cAMP, appeared not to be involved. These results suggest that changes
      in brain temperature can alter the regulation of extracellular adenosine in rat
      brain slices and that increased adenosine release may be an important regulatory
      mechanism for countering increased excitability consequent to increased brain
      temperature.

PMID- 10066247
TI  - Akt-dependent potentiation of L channels by insulin-like growth factor-1 is
      required for neuronal survival.
AB  - The insulin-like growth factor-1 (IGF-1)/receptor tyrosine kinase recently has
      been shown to mediate neuronal survival and potentiate the activity of specific
      calcium channel subtypes; survival requires Akt, a serine/threonine kinase. We
      demonstrate here that Akt mediates the IGF-1-induced potentiation of L channel
      currents, but not that of N channels. Transient expression of wild-type, dominant
      negative, and constitutively active forms of Akt in cerebellar granule neurons
      causes, respectively, no change in IGF-1/L channel potentiation, complete
      inhibition of potentiation, and a dramatic increase in basal L currents
      accompanied by the loss of ability to induce further increases. In no case is the
      IGF-1 potentiation of N currents affected. We additionally find that IGF-1
      partially mediates granule neuron survival via L channel activity and that Akt
      dependent L channel modulation is a necessary component. Interestingly, very
      brief exposure (1 min) to IGF-1 triggers nearly complete survival and requires L
      channel activity. These results strongly suggest that neuronal receptor tyrosine
      kinases can control long-term calcium-dependent processes via the rapid control
      of voltage-sensitive channels.

PMID- 10066248
TI  - Distinct signaling pathways mediate touch and osmosensory responses in a
      polymodal sensory neuron.
AB  - The Caenorhabditis elegans ASH sensory neurons mediate responses to nose touch,
      hyperosmolarity, and volatile repellent chemicals. We show here that distinct
      signaling pathways mediate the responses to touch and hyperosmolarity. ASH
      neurons distinguish between these stimuli because habituation to nose touch has
      no effect on the response to high osmolarity or volatile chemicals (1-octanol).
      Mutations in osm-10 eliminate the response to hyperosmolarity but have no effect
      on responses to nose touch or to volatile repellents. OSM-10 is a novel cytosolic
      protein expressed in ASH and three other classes of sensory neurons. Mutations in
      two other osmosensory-defective genes, eos-1 and eos-2, interact genetically with
      osm-10. Our analysis suggests that nose touch sensitivity and osmosensation occur
      via distinct signaling pathways in ASH and that OSM-10 is required for
      osmosensory signaling.

PMID- 10066249
TI  - RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's
      disease.
AB  - In this study we used an in situ approach to identify the oxidized nucleosides 8
      hydroxydeoxyguanosine (8OHdG) and 8-hydroxyguanosine (8OHG), markers of oxidative
      damage to DNA and RNA, respectively, in cases of Alzheimer's disease (AD). The
      goal was to determine whether nuclear and mitochondrial DNA as well as RNA is
      damaged in AD. Immunoreactivity with monoclonal antibodies 1F7 or 15A3
      recognizing both 8OHdG and 8OHG was prominent in the cytoplasm and to a lesser
      extent in the nucleolus and nuclear envelope in neurons within the hippocampus,
      subiculum, and entorhinal cortex as well as frontal, temporal, and occipital
      neocortex in cases of AD, whereas similar structures were immunolabeled only
      faintly in controls. Relative density measurement showed that there was a
      significant increase (p < 0.0001) in 8OHdG and 8OHG immunoreactivity with 1F7 in
      cases of AD (n = 22) as compared with senile (n = 13), presenile (n = 10), or
      young controls (n = 4). Surprisingly, the oxidized nucleoside was associated
      predominantly with RNA because immunoreaction was diminished greatly by
      preincubation in RNase but only slightly by DNase. This is the first evidence of
      increased RNA oxidation restricted to vulnerable neurons in AD. The subcellular
      localization of damaged RNA showing cytoplasmic predominance is consistent with
      the hypothesis that mitochondria may be a major source of reactive oxygen species
      that cause oxidative damage in AD.

PMID- 10066250
TI  - Myelin and collapsin-1 induce motor neuron growth cone collapse through different
      pathways: inhibition of collapse by opposing mutants of rac1.
AB  - Precise growth cone guidance is the consequence of a continuous reorganization of
      actin filament structures within filopodia and lamellipodia in response to
      inhibitory and promoting cues. The small GTPases rac1, cdc42, and rhoA are
      critical for regulating distinct actin structures in non-neuronal cells and
      presumably in growth cones. Collapse, a retraction of filopodia and lamellipodia,
      is a typical growth cone behavior on contact with inhibitory cues and is
      associated with depolymerization and redistribution of actin filaments. We
      examined whether small GTPases mediate the inhibitory properties of CNS myelin or
      collapsin-1, a soluble semaphorin, in chick embryonic motor neuron cultures. As
      demonstrated for collapsin-1, CNS myelin-evoked growth cone collapse was
      accompanied by a reduction of rhodamine-phalloidin staining most prominent in the
      growth cone periphery, suggesting actin filament disassembly. Specific mutants of
      small GTPases were capable of desensitizing growth cones to CNS myelin or
      collapsin-1. Adenoviral-mediated expression of constitutively active rac1 or rhoA
      abolished CNS myelin-induced collapse and allowed remarkable neurite extension on
      a CNS myelin substrate. In contrast, expression of dominant negative rac1 or
      cdc42 negated collapsin-1-induced growth cone collapse and promoted neurite
      outgrowth on a collapsin-1 substrate. These findings suggest that small GTPases
      can modulate the signaling pathways of inhibitory stimuli and, consequently,
      allow the manipulation of growth cone behavior. However, the fact that opposite
      mutants of rac1 were effective against different inhibitory stimuli speaks
      against a universal signaling pathway underlying growth cone collapse.

PMID- 10066251
TI  - Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines,
      coincidence detection by NMDA receptors, and optical quantal analysis.
AB  - Dendritic spines receive most excitatory inputs in the vertebrate brain, but
      their function is still poorly understood. Using two-photon calcium imaging of
      CA1 pyramidal neurons in rat hippocampal slices, we investigated the mechanisms
      by which calcium enters into individual spines in the stratum radiatum. We find
      three different pathways for calcium influx: high-threshold voltage-sensitive
      calcium channels, NMDA receptors, and an APV-resistant influx consistent with
      calcium-permeable AMPA or kainate receptors. These pathways vary among different
      populations of spines and are engaged under different stimulation conditions,
      with peak calcium concentrations reaching >10 microM. Furthermore, as a result of
      the biophysical properties of the NMDA receptor, the calcium dynamics of spines
      are exquisitely sensitive to the temporal coincidence of the input and output of
      the neuron. Our results confirm that individual spines are chemical compartments
      that can perform coincidence detection. Finally, we demonstrate that functional
      studies and optical quantal analysis of single, identified synapses is feasible
      in mammalian CNS neurons in brain slices.

PMID- 10066252
TI  - Modification of postsynaptic densities after transient cerebral ischemia: a
      quantitative and three-dimensional ultrastructural study.
AB  - Abnormal synaptic transmission has been hypothesized to be a cause of neuronal
      death resulting from transient ischemia, although the mechanisms are not fully
      understood. Here, we present evidence that synapses are markedly modified in the
      hippocampus after transient cerebral ischemia. Using both conventional and high
      voltage electron microscopy, we performed two- and three-dimensional analyses of
      synapses selectively stained with ethanolic phosphotungstic acid in the
      hippocampus of rats subjected to 15 min of ischemia followed by various periods
      of reperfusion. Postsynaptic densities (PSDs) from both area CA1 and the dentate
      gyrus were thicker and fluffier in postischemic hippocampus than in controls.
      Three-dimensional reconstructions of selectively stained PSDs created using
      electron tomography indicated that postsynaptic densities became more irregular
      and loosely configured in postischemic brains compared with those in controls. A
      quantitative study based on thin sections of the time course of PSD modification
      indicated that the increase in thickness was both greater and more long-lived in
      area CA1 than in dentate gyrus. Whereas the magnitude of morphological change in
      dentate gyrus peaked at 4 hr of reperfusion (140% of control values) and declined
      thereafter, changes in area CA1 persisted and increased at 24 hr of reperfusion
      (191% of control values). We hypothesize that the degenerative ultrastructural
      alteration of PSDs may produce a toxic signal such as a greater calcium influx,
      which is integrated from the thousands of excitatory synapses onto dendrites, and
      is propagated to the neuronal somata where it causes or contributes to neuronal
      damage during the postischemic phase.

PMID- 10066253
TI  - Metabolic stabilization of muscle nicotinic acetylcholine receptor by rapsyn.
AB  - Although the metabolic half-life of muscle endplate acetylcholine receptor (AChR)
      changes during development and after denervation in the adult, little is known
      about the molecular mechanisms that influence receptor stability. We have
      investigated the effect on AChR turnover of its interaction with rapsyn, a 43 kDa
      peripheral membrane protein that is closely associated with the AChR in muscle
      cells and is required for its clustering at endplates. Both in transfected COS
      cells and in cultured myotubes from rapsyn-negative and rapsyn-positive mice, we
      have found that the presence of rapsyn slows the turnover of AChRs by as much as
      twofold. The effect was similar for both embryonic (alpha2betadeltagamma) and
      adult (alpha2betadeltaepsilon) AChRs and for AChRs whose beta subunit lacked a
      putative tyrosine phosphorylation site. Neither colchicine nor cytochalasin D
      altered AChR turnover or prevented the rapsyn effect. Mutant rapsyn proteins
      whose N-terminal myristoylation signal was eliminated, or whose C terminus or
      zinc-finger domains were deleted, failed to change the rate of receptor turnover.
      Each of these mutations affects the association of the AChR with rapsyn,
      suggesting that AChR stability is altered by interaction between the two
      proteins. Our results suggest that, in addition to its role in AChR clustering,
      rapsyn also functions to metabolically stabilize the AChR.

PMID- 10066254
TI  - Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic
      spinal cord neurons but requires transforming growth factor-beta as cofactor in
      vivo.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic
      factor for several populations of CNS and peripheral neurons. Synthesis and
      storage of GDNF by the neuron-like adrenal medullary cells suggest roles in
      adrenal functions and/or in the maintenance of spinal cord neurons that innervate
      the adrenal medulla. We show that unilateral adrenomedullectomy causes
      degeneration of all sympathetic preganglionic neurons within the
      intermediolateral column (IML) of spinal cord segments T7-T10 that project to the
      adrenal medulla. In situ hybridization revealed that IML neurons express the
      glycosylphosphatidylinositol-linked alpha receptor 1 and c-Ret receptors, which
      are essential for GDNF signaling. IML neurons also display immunoreactivity for
      transforming growth factor-beta (TGF-beta) receptor II. Administration of GDNF
      (recombinant human, 1 microg) in Gelfoam implanted into the medullectomized
      adrenal gland rescued all Fluoro-Gold-labeled preganglionic neurons projecting to
      the adrenal medulla after four weeks. Cytochrome c applied as a control protein
      was not effective. The protective effect of GDNF was prevented by co
      administration to the Gelfoam of neutralizing antibodies recognizing all three
      TGF-beta isoforms but not GDNF. This suggests that the presence of endogenous TGF
      beta was essential for permitting a neurotrophic effect of GDNF. Our data
      indicate that GDNF has a capacity to protect a population of autonomic spinal
      cord neurons from target-deprived cell death. Furthermore, our results
      demonstrate for the first time that the previously reported requirement of TGF
      beta for permitting trophic actions of GDNF in vitro (Kreiglstein et al., 1998)
      also applies to the in vivo situation.

PMID- 10066255
TI  - Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced
      product of the RGS9 gene.
AB  - Regulators of G-protein signaling (RGS) proteins act as GTPase-activating
      proteins (GAPs) for alpha subunits of heterotrimeric G-proteins. Previous in situ
      hybridization analysis of mRNAs encoding RGS3-RGS11 revealed region-specific
      expression patterns in rat brain. RGS9 showed a particularly striking pattern of
      almost exclusive enrichment in striatum. In a parallel study, RGS9 cDNA, here
      referred to as RGS9-1, was cloned from retinal cDNA libraries, and the encoded
      protein was identified as a GAP for transducin (Galphat) in rod outer segments.
      In the present study we identify a novel splice variant of RGS9, RGS9-2, cloned
      from a mouse forebrain cDNA library, which encodes a striatal-specific isoform of
      the protein. RGS9-2 is 191 amino acids longer than the retinal isoform, has a
      unique 3' untranslated region, and is highly enriched in striatum, with much
      lower levels seen in other brain regions and no expression detectable in retina.
      Immunohistochemistry showed that RGS9-2 protein is restricted to striatal
      neuropil and absent in striatal terminal fields. The functional activity of RGS9
      2 is supported by the finding that it, but not RGS9-1, dampens the Gi/o-coupled
      mu-opioid receptor response in vitro. Characterization of a bacterial artificial
      chromosome genomic clone of approximately 200 kb indicates that these isoforms
      represent alternatively spliced mRNAs from a single gene and that the RGS domain,
      conserved among all known RGS members, is encoded over three distinct exons. The
      distinct C-terminal domains of RGS9-2 and RGS9-1 presumably contribute to unique
      regulatory properties in the neural and retinal cells in which these proteins are
      selectively expressed.

PMID- 10066256
TI  - Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the
      intermediate compartment and affects the transport of the wild-type protein by
      direct interaction.
AB  - Peripheral myelin protein 22 (PMP22) is an integral membrane protein that is
      essential for the normal formation and maintenance of peripheral myelin.
      Duplications, deletions, or mutations in the PMP22 gene account for a set of
      dominantly inherited peripheral neuropathies. The heterozygous Trembler-J (TrJ)
      genotype in mice is similar genetically to a Charcot-Marie-Tooth disease type 1A
      pedigree in humans, whereas the homozygous TrJ condition leads to the most severe
      form of PMP22-associated neuropathies. To characterize the consequences of the
      TrJ mutation, we labeled wild-type (wt-) and TrJ-PMP22 in the third loop of the
      protein with different epitope tags and expressed them separately or together in
      COS7 cells and primary Schwann cells. Here we show that the transport of the
      mutant TrJ-PMP22 is interrupted in the intermediate compartment, preventing its
      insertion into the plasma membrane and affecting the morphology of the
      endoplasmic reticulum. In addition, TrJ-PMP22 forms a heterodimer with the wt
      PMP22. This interaction causes a fraction of the wt-PMP22 to be retained with TrJ
      PMP22 in the intermediate compartment of COS7 and Schwann cells. The relative
      stability of a wt-mutant PMP22 heterodimer as compared with the wt-wt PMP22
      homodimer may determine whether a particular mutation is semidominant or
      dominant. The neuropathy itself appears to result both from decreased trafficking
      of wt-PMP22 to the plasma membrane and from a toxic gain of function via the
      accumulation of wt- and TrJ-PMP22 in the intermediate compartment.

PMID- 10066257
TI  - GABA- and glutamate-activated channels in green fluorescent protein-tagged
      gonadotropin-releasing hormone neurons in transgenic mice.
AB  - Mice were generated expressing green fluorescent protein (GFP) under the control
      of the gonadotropin-releasing hormone (GnRH) promoter. Green fluorescence was
      observed in, and restricted to, GnRH-immunopositive neuronal somata in the
      olfactory bulb, ganglion terminale, septal nuclei, diagonal band of Broca (DBB),
      preoptic area (POA), and caudal hypothalamus, as well as GnRH neuronal dendrites
      and axons, including axon terminals in the median eminence and organum vasculosum
      of the lamina terminalis (OVLT). Whole-cell recordings from GFP-expressing GnRH
      neurons in the OVLT-POA-DBB region revealed a firing pattern among GFP-expressing
      GnRH neurons distinct from that of nonfluorescent neurons. Nucleated patches of
      GFP-expressing GnRH neurons exhibited pronounced responses to fast application of
      GABA and smaller responses to L-glutamate and AMPA. One-fifth of the nucleated
      patches responded to NMDA. The GABA-A, AMPA, and NMDA receptor channels on GnRH
      neurons mediating these responses may play a role in the modulation of GnRH
      secretory oscillations.

PMID- 10066258
TI  - The 5'-flanking region of the mouse adenylyl cyclase type VIII gene imparts
      tissue-specific expression in transgenic mice.
AB  - The calcium-stimulated adenylyl cyclases (ACs) play a central role in stimulus
      dependent modification of synaptic function. The type VIII AC (AC8) is one of
      three mammalian calcium-stimulated isoforms, each of which is expressed in a
      region-specific manner in the CNS. To delineate the DNA sequences responsible for
      appropriate targeting of AC8 expression, we report here the complete structure of
      the AC8 gene and define the pattern of expression of the full-length cDNA and its
      splice variants. In addition to expression within the brain, robust expression of
      AC8 was also found in the lung. By in situ hybridization, we have found the
      highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula,
      cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei. By
      generating transgenic mice whose expression of beta-galactosidase is controlled
      by the AC8 5'-flanking DNA sequences, we demonstrate that the DNA sequences
      within the 10 kb preceding exon 1 are critical for establishment of this region
      specific pattern. This spectrum of sites of production is unique to AC8 among the
      calcium-stimulated adenylyl cyclases and suggests nonredundant functions with
      other adenylyl cyclases in neuroendocrine regulation and/or behavior.

PMID- 10066259
TI  - A role for insulin-like growth factor-I in the regulation of Schwann cell
      survival.
AB  - During postnatal development in the peripheral nerve, differentiating Schwann
      cells are susceptible to apoptotic death. Schwann cell apoptosis is regulated by
      axons and serves as one mechanism through which axon and Schwann cell numbers are
      correctly matched. This regulation is mediated in part by the provision of
      limiting axon-derived trophic molecules, although neuregulin-1 (NRG-1) is the
      only trophic factor shown to date to support Schwann cell survival. In this
      report, we identify insulin-like growth factor-I (IGF-I) as an additional trophin
      that can promote Schwann cell survival in vitro. We find that IGF-I, like NRG-1,
      can prevent the apoptotic death of postnatal rat Schwann cells cultured under
      conditions of serum withdrawal. Moreover, we show that differentiating Schwann
      cells in the rat sciatic nerve express both the IGF-I receptor (IGF-I R) and IGF
      I throughout postnatal development. These results indicate that IGF-I is likely
      to control Schwann cell viability in the developing peripheral nerve and,
      together with other findings, raise the interesting possibility that such
      survival regulation may switch during postnatal development from an axon
      dependent mechanism to an autocrine and/or paracrine one.

PMID- 10066260
TI  - Differential sorting of nerve growth factor and brain-derived neurotrophic factor
      in hippocampal neurons.
AB  - Nerve growth factor (NGF) is released through the constitutive secretory pathway
      from cells in peripheral tissues and nerves where it can act as a target-derived
      survival factor. In contrast, brain-derived neurotrophic factor (BDNF) appears to
      be processed in the regulated secretory pathway of brain neurons and secreted in
      an activity-dependent manner to play a role in synaptic plasticity. To determine
      whether sorting differences are intrinsic to the neurotrophins or reflect
      differences between cell types, we compared NGF and BDNF processing in cultured
      hippocampal neurons using a Vaccinia virus expression system. Three independent
      criteria (retention or release from cells after pulse-chase labeling,
      depolarization-dependent release, and immunocytochemical localization) suggest
      that the bulk of newly synthesized NGF is sorted into the constitutive pathway,
      whereas BDNF is primarily sorted into the regulated secretory pathway. Similar
      results occurred with AtT 20 cells, including those transfected with cDNAs
      encoding neurotrophin precursor-green fluorescent protein fusions. The NGF
      precursor, but not the BDNF precursor, is efficiently cleaved by the endoprotease
      furin in the trans-Golgi network (TGN). Blocking furin activity in AtT 20 cells
      with alpha1-PDX as well as increasing the expression of NGF precursor partially
      directed NGF into the regulated secretory pathway. Therefore, neurotrophins can
      be sorted into either the constitutive or regulated secretory pathways, and
      sorting may be regulated by the efficiency of furin cleavage in the TGN. This
      mechanism may explain how neuron-generated neurotrophins can act both as survival
      factors and as neuropeptides.

PMID- 10066261
TI  - The distribution of neurons expressing calcium-permeable AMPA receptors in the
      superficial laminae of the spinal cord dorsal horn.
AB  - The superficial dorsal horn is a major site of termination of nociceptive primary
      afferents. Fast excitatory synaptic transmission in this region is mediated
      mainly by release of glutamate onto postsynaptic AMPA and NMDA receptors. NMDA
      receptors are known to be Ca2+-permeable and to provide synaptically localized
      Ca2+ signals that mediate short-term and long-term changes in synaptic strength.
      Less well known is a subpopulation of AMPA receptors that is Ca2+-permeable and
      has been shown to be synaptically localized on dorsal horn neurons in culture (Gu
      et al., 1996) and expressed by dorsal horn neurons in situ (Nagy et al., 1994;
      Engelman et al., 1997). We used kainate-induced cobalt uptake as a functional
      marker of neurons expressing Ca2+-permeable AMPA receptors and combined this with
      markers of nociceptive primary afferents in the postnatal rat dorsal horn. We
      have shown that cobalt-positive neurons are located in lamina I and outer lamina
      II, a region strongly innervated by nociceptors. These cobalt-positive neurons
      colocalize with afferents labeled by LD2, and with the most dorsal region of
      capsaicin-sensitive and IB4- and LA4-positive afferents. In contrast, inner
      lamina II has a sparser distribution of cobalt-positive neurons. Some lamina I
      neurons expressing the NK1 receptor, the receptor for substance P, are also
      cobalt positive. These neurons are likely to be projection neurons in the
      nociceptive pathway. On the basis of all of these observations, we propose that
      Ca2+-permeable AMPA receptors are localized to mediate transmission of
      nociceptive information.

PMID- 10066262
TI  - Specification of distinct dopaminergic neural pathways: roles of the Eph family
      receptor EphB1 and ligand ephrin-B2.
AB  - Dopaminergic neurons in the substantia nigra and ventral tegmental area project
      to the caudate putamen and nucleus accumbens/olfactory tubercle, respectively,
      constituting mesostriatal and mesolimbic pathways. The molecular signals that
      confer target specificity of different dopaminergic neurons are not known. We now
      report that EphB1 and ephrin-B2, a receptor and ligand of the Eph family, are
      candidate guidance molecules for the development of these distinct pathways.
      EphB1 and ephrin-B2 are expressed in complementary patterns in the midbrain
      dopaminergic neurons and their targets, and the ligand specifically inhibits the
      growth of neurites and induces the cell loss of substantia nigra, but not ventral
      tegmental, dopaminergic neurons. These studies suggest that the ligand-receptor
      pair may contribute to the establishment of distinct neural pathways by
      selectively inhibiting the neurite outgrowth and cell survival of mistargeted
      neurons. In addition, we show that ephrin-B2 expression is upregulated by cocaine
      and amphetamine in adult mice, suggesting that ephrin-B2/EphB1 interaction may
      play a role in drug-induced plasticity in adults as well.

PMID- 10066263
TI  - Spontaneous network activity transiently depresses synaptic transmission in the
      embryonic chick spinal cord.
AB  - We examined the effects of spontaneous or evoked episodes of rhythmic activity on
      synaptic transmission in several spinal pathways of embryonic day 9-12 chick
      embryos. We compared the amplitude of synaptic potentials evoked by stimulation
      of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and
      after episodes of activity. With the exception of the short-latency responses
      evoked by dorsal root stimulation, the potentials were briefly potentiated and
      then reduced for several minutes after an episode of rhythmic activity. Their
      amplitude progressively recovered in the interval between successive episodes.
      The lack of post-episode depression in the short-latency component of the dorsal
      root evoked responses is probably attributable to the absence of firing in cut
      muscle afferents during an episode of activity. The post-episode depression of
      VLF-evoked potentials was mimicked by prolonged stimulation of the VLF,
      subthreshold for an episode of activity. By contrast, antidromically induced
      motoneuron firing and the accompanying calcium entry did not depress VLF-evoked
      potentials recorded from the stimulated ventral root. In addition, post-episode
      depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal
      neurons. Collectively, these findings suggest that somatic postsynaptic activity
      and calcium entry are not required for the depression. We propose instead that
      the mechanism may involve a form of long-lasting activity-induced synaptic
      depression, possibly a combination of transmitter depletion and ligand-induced
      changes in the postsynaptic current accompanying transmitter release. This
      activity-dependent depression appears to be an important mechanism underlying the
      occurrence of spontaneous activity in developing spinal networks.

PMID- 10066264
TI  - Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic
      retraction in cultured rat sympathetic neurons.
AB  - Dendritic retraction occurs in many regions of the developing brain and also
      after neural injury. However, the molecules that regulate this important
      regressive process remain largely unknown. Our data indicate that leukemia
      inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympathetic
      neurons to retract their dendrites in vitro, ultimately leading to an
      approximately 80% reduction in the size of the arbor. The dendritic retraction
      induced by LIF exhibited substantial specificity because it was not accompanied
      by changes in cell number, in the rate of axonal growth, or in the expression of
      axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and
      CNTF, and both cytokines induced phosphorylation and nuclear translocation of
      stat3. Moreover, addition of soluble interleukin-6 (IL-6) receptor to the medium
      endowed IL-6 with the ability to cause dendritic regression. These data indicate
      that ligands activating the gp130 pathway have the ability to profoundly alter
      neuronal cell shape and polarity by selectively causing the retraction of
      dendrites.

PMID- 10066265
TI  - Brain-derived neurotrophic factor prevents low-frequency inputs from inducing
      long-term depression in the developing visual cortex.
AB  - Brain-derived neurotrophic factor (BDNF) is reported to enhance synaptic
      transmission and to play a role in long-term potentiation in hippocampus and
      neocortex. If so, a shortage or blockade of BDNF might lead to another form of
      synaptic plasticity, long-term depression (LTD). To test this possibility and to
      elucidate mechanisms if it is the case, EPSCs evoked by test stimulation of layer
      IV were recorded from layer II/III neurons in visual cortical slices of young
      rats in the whole-cell voltage-clamp mode. LTD was induced by low-frequency
      stimulation (LFS) at 1 Hz for 10-15 min if each pulse of the LFS was paired with
      depolarization of neurons to -30 mV but was not induced if their membrane
      potentials were kept at -70 mV. Such an LTD was blocked by exogenously applied
      BDNF, probably through presynaptic mechanisms. Suppression of endogenous BDNF
      activity by the anti-BDNF antibody or an inhibitor for BDNF receptors made
      otherwise ineffective stimuli (LFS without postsynaptic depolarization) effective
      for LTD induction, suggesting that endogenous BDNF may prevent low-frequency
      inputs from inducing LTD in the developing visual cortex.

PMID- 10066266
TI  - BDNF is a target-derived survival factor for arterial baroreceptor and
      chemoafferent primary sensory neurons.
AB  - Brain-derived neurotrophic factor (BDNF) supports survival of 50% of visceral
      afferent neurons in the nodose/petrosal sensory ganglion complex (NPG; Ernfors et
      al., 1994a; Jones et al., 1994; Conover et al., 1995; Liu et al., 1995; Erickson
      et al., 1996), including arterial chemoafferents that innervate the carotid body
      and are required for development of normal breathing (Erickson et al., 1996).
      However, the relationship between BDNF dependence of visceral afferents and the
      location and timing of BDNF expression in visceral tissues is unknown. The
      present study demonstrates that BDNF mRNA and protein are transiently expressed
      in NPG targets in the fetal cardiac outflow tract, including baroreceptor regions
      in the aortic arch, carotid sinus, and right subclavian artery, as well as in the
      carotid body. The period of BDNF expression corresponds to the onset of sensory
      innervation and to the time at which fetal NPG neurons are BDNF-dependent in
      vitro. Moreover, baroreceptor innervation is absent in newborn mice lacking BDNF.
      In addition to vascular targets, vascular afferents themselves express high
      levels of BDNF, both during and after the time they are BDNF-dependent. However,
      endogenous BDNF supports survival of fetal NPG neurons in vitro only under
      depolarizing conditions. Together, these data indicate two roles for BDNF during
      vascular afferent pathway development; initially, as a target-derived survival
      factor, and subsequently, as a signaling molecule produced by the afferents
      themselves. Furthermore, the fact that BDNF is required for survival of
      functionally distinct populations of vascular afferents demonstrates that trophic
      requirements of NPG neurons are not modality-specific but may instead be
      associated with innervation of particular organ systems.

PMID- 10066267
TI  - Proteolipid protein gene product can be secreted and exhibit biological activity
      during early development.
AB  - A gene encoding myelin proteolipid protein (PLP) and its smaller isoform DM20 is
      expressed at least 1 week before myelination. Mutations within the gene cause
      abnormalities in the development of premyelinating oligodendrocytes, resulting in
      hypomyelinating disorders. These findings suggest a premyelinating function of
      the PLP gene products. We previously demonstrated that PLP gene expression is
      directly associated with secretion of a factor that increases the number of
      oligodendrocytes. Here we show that this activity is mediated by a secreted
      fragment containing the C-terminal portion of PLP. This factor increased the
      bromodeoxyuridine incorporation rate in both oligodendrocyte and astrocyte
      lineage cells; a synthetic peptide (PLP 215-232) exhibited a similar activity.
      Dose-response curves of PLP and PLP peptide showed maximum activities at a
      concentration in the picomolar range, which decreased at higher concentrations.
      These observations demonstrate that a secreted PLP gene product exerts biological
      activity at a premyelinating stage before the major induction of the gene.

PMID- 10066268
TI  - Orphanin-FQ/nociceptin (OFQ/N) modulates the activity of suprachiasmatic nucleus
      neurons.
AB  - Neurons in the suprachiasmatic nucleus (SCN) constitute the principal circadian
      pacemaker of mammals. In situ hybridization studies revealed expression of
      orphanin-FQ/nociceptin (OFQ/N) receptor (NOR) mRNA in the SCN, whereas no
      expression of mRNA for preproOFQ/N (ppOFQ/N) was detected. The presence of OFQ/N
      peptide in the SCN was demonstrated by radioimmunoassay. SCN neurons (88%)
      responded dose-dependently to OFQ/N with an outward current (EC50 = 22.3 nM) that
      was reduced in amplitude by membrane hyperpolarization and reversed polarity near
      the theoretical potassium equilibrium potential. [Phe1psi(Ch2-NH)Gly2]OFQ/N(1
      13)NH2 (3 microM), a putative NOR antagonist, activated a small outward current
      and significantly reduced the amplitude of the OFQ/N-stimulated current. OFQ/N
      reduced the NMDA receptor-mediated increase in intracellular Ca2+. When injected
      unilaterally into the SCN of Syrian hamsters housed in constant darkness, OFQ/N
      (1-50 pmol) failed to alter the timing of the hamsters' wheel-running activity.
      However, injection of OFQ/N (0.1-50 pmol) before a brief exposure to light during
      the midsubjective night significantly attenuated the light-induced phase advances
      of the activity rhythm. These data are consistent with the interpretation that
      OFQ/N acting at specific receptors modulates the activity of SCN neurons and,
      thereby, the response of the circadian clock to light.

PMID- 10066269
TI  - Immunocytochemical and morphological evidence for intracellular self-repair as an
      important contributor to mammalian hair cell recovery.
AB  - Although recent studies have provided evidence for hair cell regeneration in
      mammalian inner ears, the mechanism underlying this regenerative process is still
      under debate. Here we report immunocytochemical, histological, electron
      microscopic, and autoradiographic evidence that, in cultured postnatal rat
      utricles, a substantial number of hair cells can survive gentamicin insult even
      their stereocilia are lost. These partially damaged hair cells can survive for a
      prolonged time and regrow the stereocilia. Although the number of stereocilia
      bearing hair cells increases over time after gentamicin insult, hair cell and
      supporting cell numbers remain essentially unchanged. Tritiated thymidine
      autoradiography and bromodeoxyuridine immunocytochemistry of the cultures
      demonstrate that cell proliferation in the sensory epithelium is very limited and
      is far below the number of recovered hair cells. Furthermore, terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling analysis
      indicates that gentamicin-induced apoptosis in the sensory epithelium occurs
      mainly during a 2 d treatment period, and additional cell death is minimal 2-11 d
      after treatment. Considered together, intracellular repair of partially damaged
      hair cells can be an important contributor to spontaneous hair cell recovery in
      mammalian inner ears.

PMID- 10066270
TI  - Adult subventricular zone neuronal precursors continue to proliferate and migrate
      in the absence of the olfactory bulb.
AB  - Neurons continue to be born in the subventricular zone (SVZ) of the lateral
      ventricles of adult mice. These cells migrate as a network of chains through the
      SVZ and the rostral migratory stream (RMS) into the olfactory bulb (OB), where
      they differentiate into mature neurons. The OB is the only known target for these
      neuronal precursors. Here, we show that, after elimination of the OB, the SVZ and
      RMS persist and become dramatically larger. The proportion of dividing
      [bromodeoxyuridine (BrdU)-labeled] or dying (pyknotic or terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeled) cells in
      the RMS was not significantly affected at 3 d or 3 weeks after bulbectomy (OBX).
      However, by 3 months after OBX, the percentage of BrdU-labeled cells in the RMS
      decreased by half and that of dying cells doubled. Surprisingly, the rostral
      migration of precursors continued along the RMS after OBX. This was demonstrated
      by focal microinjections of BrdU and grafts of SVZ cells carrying LacZ under the
      control of a neuron-specific promoter gene. Results indicate that the OB is not
      essential for proliferation and the directional migration of SVZ precursors.

PMID- 10066271
TI  - Role of protein kinase A in the maintenance of inflammatory pain.
AB  - Although the initiation of inflammatory pain (hyperalgesia) has been demonstrated
      to require the cAMP second messenger signaling cascade, whether this mechanism
      and/or other mechanisms underlie the continued maintenance of the induced
      hyperalgesia is unknown. We report that injection of adenylyl cyclase inhibitors
      before but not after injection of direct-acting hyperalgesic agents
      (prostaglandin E2 and purine and serotonin receptor agonists) resulted in
      reduction in hyperalgesia, evaluated by the Randall-Selitto paw-withdrawal test.
      In contrast, injection of protein kinase A (PKA) inhibitors either before or
      after these hyperalgesic agents resulted in reduced hyperalgesia, suggesting that
      hyperalgesia after its activation was maintained by persistent PKA activity but
      not by adenylyl cyclase activity. To evaluate further the role of PKA activity in
      the maintenance of hyperalgesia, we injected the catalytic subunit of PKA (PKACS)
      that resulted in hyperalgesia similar in magnitude to that induced by the direct
      acting hyperalgesic agents but much longer in duration (>48 vs 2 hr). Injection
      of WIPTIDE (a PKA inhibitor) at 24 hr after PKACS reduced hyperalgesia,
      suggesting that PKACS hyperalgesia is not independently maintained by steps
      downstream from PKA. In summary, our results indicate that, once established,
      inflammatory mediator-induced hyperalgesia is no longer maintained by adenylyl
      cyclase activity but rather is dependent on ongoing PKA activity. An
      understanding of the mechanism maintaining hyperalgesia may provide important
      insight into targets for the treatment of persistent pain.

PMID- 10066272
TI  - Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats.
AB  - Previous reports indicate that growth hormone-releasing hormone (GHRH) is
      involved in sleep regulation. The site of action mediating the nonrapid eye
      movement sleep (NREMS)-promoting effects of GHRH is not known, but it is
      independent from the pituitary. GHRH (0.001, 0. 01, and 0.1 nmol/kg) or a
      competitive antagonist of GHRH (0.003, 0.3, and 14 nmol/kg) was microinjected
      into the preoptic area, and the sleep-wake activity was recorded for 23 hr after
      injection in rats. GHRH elicited dose-dependent increases in the duration and in
      the intensity of NREMS compared with that in control records after intrapreoptic
      injection of physiological saline. The antagonist decreased the duration and
      intensity of NREMS and prolonged sleep latency. Consistent alterations in rapid
      eye movement sleep (REMS) and in brain temperature were not found. The GHRH
      antagonist also attenuated the enhancements in NREMS elicited by 3 hr of sleep
      deprivation. Histological verification of the injection sites showed that the
      majority of the effective injections were in the preoptic area and the diagonal
      band of Broca. The results indicate that the preoptic area mediates the sleep
      promoting activity of GHRH.

PMID- 10066273
TI  - Transient potassium currents regulate the discharge patterns of dorsal cochlear
      nucleus pyramidal cells.
AB  - Pyramidal cells in the dorsal cochlear nucleus (DCN) show three distinct temporal
      discharge patterns in response to sound: "pauser," "buildup," and "chopper."
      Similar discharge patterns are seen in vitro and depend on the voltage from which
      the cell is depolarized. It has been proposed that an inactivating A-type K+
      current (IKI) might play a critical role in generating the three different
      patterns. In this study we examined the characteristics of transient currents in
      DCN pyramidal cells to evaluate this hypothesis. Morphologically identified
      pyramidal cells in rat brain slices (P11-P17) exhibited the three voltage
      dependent discharge patterns. Two inactivating currents were present in outside
      out patches from pyramidal cells: a rapidly inactivating (IKIF, tau approximately
      11 msec) current insensitive to block by tetraethylammonium (TEA) and variably
      blocked by 4-aminopyridine (4-AP) with half-inactivation near -85 mV, and a
      slowly inactivating TEA- and 4-AP-sensitive current (IKIS, tau approximately 145
      msec) with half-inactivation near -35 mV. Recovery from inactivation at 34
      degrees C was described by a single exponential with a time constant of 10-30
      msec, similar to the rate at which first spike latency increases with the
      duration of a hyperpolarizing prepulse. Acutely isolated cells also possessed a
      rapidly activating (<1 msec at 22 degrees C) transient current that activated
      near -45 mV and showed half-inactivation near -80 mV. A model demonstrated that
      the deinactivation of IKIF was correlated with the discharge patterns. Overall,
      the properties of the fast inactivating K+ current were consistent with their
      proposed role in shaping the discharge pattern of DCN pyramidal cells.

PMID- 10066274
TI  - Cellular mechanisms contributing to response variability of cortical neurons in
      vivo.
AB  - Cortical neurons recorded in vivo exhibit highly variable responses to the
      repeated presentation of the same stimulus. To further understand the cellular
      mechanisms underlying this phenomenon, we performed intracellular recordings from
      neurons in cat striate cortex in vivo and examined the relationships between
      spontaneous activity and visually evoked responses. Activity was assessed on a
      trial-by-trial basis by measuring the membrane potential (Vm) fluctuations and
      spike activity during brief epochs immediately before and after the onset of an
      evoked response. We found that the response magnitude, expressed as a change in
      Vm relative to baseline, was linearly correlated with the preceding spontaneous
      Vm. This correlation was enhanced when the cells were hyperpolarized to reduce
      the activation of voltage-gated conductances. The output of the cells, expressed
      as spike counts and latencies, was only moderately correlated with fluctuations
      in the preceding spontaneous Vm. Spike-triggered averaging of Vm revealed that
      visually evoked action potentials arise from transient depolarizations having a
      rise time of approximately 10 msec. Consistent with this, evoked spike count was
      found to be linearly correlated with the magnitude of Vm fluctuations in the
      gamma (20-70 Hz) frequency band. We also found that the threshold of visually
      evoked action potentials varied over a range of approximately 10 mV. Examination
      of simultaneously recorded intracellular and extracellular activity revealed a
      correlation between Vm depolarization and spike discharges in adjacent cells.
      Together these results demonstrate that response variability is attributable
      largely to coherent fluctuations in cortical activity preceding the onset of a
      stimulus, but also to variations in action potential threshold and the magnitude
      of high-frequency fluctuations evoked by the stimulus.

PMID- 10066275
TI  - Visual motion analysis for pursuit eye movements in area MT of macaque monkeys.
AB  - We asked whether the dynamics of target motion are represented in visual area MT
      and how information about image velocity and acceleration might be extracted from
      the population responses in area MT for use in motor control. The time course of
      MT neuron responses was recorded in anesthetized macaque monkeys during target
      motions that covered the range of dynamics normally seen during smooth pursuit
      eye movements. When the target motion provided steps of target speed, MT neurons
      showed a continuum from purely tonic responses to those with large transient
      pulses of firing at the onset of motion. Cells with large transient responses for
      steps of target speed also had larger responses for smooth accelerations than for
      decelerations through the same range of target speeds. Condition-test experiments
      with pairs of 64 msec pulses of target speed revealed response attenuation at
      short interpulse intervals in cells with large transient responses. For
      sinusoidal modulation of target speed, MT neuron responses were strongly
      modulated for frequencies up to, but not higher than, 8 Hz. The phase of the
      responses was consistent with a 90 msec time delay between target velocity and
      firing rate. We created a model that reproduced the dynamic responses of MT cells
      using divisive gain control, used the model to visualize the population response
      in MT to individual stimuli, and devised weighted-averaging computations to
      reconstruct target speed and acceleration from the population response. Target
      speed could be reconstructed if each neuron's output was weighted according to
      its preferred speed. Target acceleration could be reconstructed if each neuron's
      output was weighted according to the product of preferred speed and a measure of
      the size of its transient response.

PMID- 10066276
TI  - In vitro analog of operant conditioning in aplysia. I. Contingent reinforcement
      modifies the functional dynamics of an identified neuron.
AB  - Previously, an analog of operant conditioning in Aplysia was developed using the
      rhythmic motor activity in the isolated buccal ganglia. This analog expressed a
      key feature of operant conditioning, namely a selective enhancement in the
      occurrence of a designated motor pattern by contingent reinforcement. Different
      motor patterns generated by the buccal central pattern generator were induced by
      monotonic stimulation of a peripheral nerve (i.e., n.2,3). Phasic stimulation of
      the esophageal nerve (E n.) was used as an analog of reinforcement. The present
      study investigated the neuronal mechanisms associated with the genesis of
      different motor patterns and their modifications by contingent reinforcement. The
      genesis of different motor patterns was related to changes in the functional
      states of the pre-motor neuron B51. During rhythmic activity, B51 dynamically
      switched between inactive and active states. Bursting activity in B51 was
      associated with, and predicted, characteristic features of a specific motor
      pattern (i.e., pattern I). Contingent reinforcement of pattern I modified the
      dynamical properties of B51 by decreasing its resting conductance and threshold
      for eliciting plateau potentials and thus increased the occurrences of pattern I
      related activity in B51. These modifications were not observed in preparations
      that received either noncontingent reinforcement (i.e., yoke control) or no
      reinforcement (i.e., control). These results suggest that a contingent
      reinforcement paradigm can regulate the dynamics of neuronal activity that is
      centrally programmed by the intrinsic cellular properties of neurons.

PMID- 10066277
TI  - In vitro analog of operant conditioning in aplysia. II. Modifications of the
      functional dynamics of an identified neuron contribute to motor pattern
      selection.
AB  - Previously, an analog of operant conditioning was developed using the buccal
      ganglia of Aplysia, the probabilistic occurrences of a specific motor pattern
      (i.e., pattern I), a contingent reinforcement (i.e., stimulation of the
      esophageal nerve), and monotonic stimulation of a peripheral nerve (i.e., n.2,3).
      This analog expressed a key feature of operant conditioning (i.e., selective
      enhancement of the probability of occurrence of a designated motor pattern by
      contingent reinforcement). In addition, the training induced changes in the
      dynamical properties of neuron B51, an element of the buccal central pattern
      generator. To gain insights into the neuronal mechanisms that mediate features of
      operant conditioning, the present study identified a neuronal element that was
      critically involved in the selective enhancement of pattern I. We found that
      bursting activity in cell B51 contributed significantly to the expression of
      pattern I and that changes in the dynamical properties of this cell were
      associated with the selective enhancement of pattern I. These changes could be
      induced by an explicit association of reinforcement with random depolarization of
      B51. No stimulation of n.2,3 was required. These results indicate that the
      selection of a designated motor pattern by contingent reinforcement and the
      underlying neuronal plasticity resulted from the association of reinforcement
      with a component of central neuronal activity that contributes to a specific
      motor pattern. The sensory stimulus that allows for occurrences of different
      motor acts may not be critical for induction of plasticity that mediates the
      selection of a motor output by contingent reinforcement in operant conditioning.

PMID- 10066278
TI  - Coding of sound envelopes by inhibitory rebound in neurons of the superior
      olivary complex in the unanesthetized rabbit.
AB  - Most natural sounds (e.g., speech) are complex and have amplitude envelopes that
      fluctuate rapidly. A number of studies have examined the neural coding of
      envelopes, but little attention has been paid to the superior olivary complex
      (SOC), a constellation of nuclei that receive information from the cochlear
      nucleus. We studied two classes of predominantly monaural neurons: those that
      displayed a sustained response to tone bursts and those that gave only a response
      to the tone offset. Our results demonstrate that the off neurons in the SOC can
      encode the pattern of amplitude-modulated sounds with high synchrony that is
      superior to sustained neurons. The upper cutoff frequency and highest modulation
      frequency at which significant synchrony was present were, on average, slightly
      higher for off neurons compared with sustained neurons. Finally, most sustained
      and off neurons encoded the level of pure tones over a wider range of intensities
      than those reported for auditory nerve fibers and cochlear nucleus neurons. A
      traditional view of inhibition is that it attenuates or terminates neural
      activity. Although this holds true for off neurons, the robust discharge when
      inhibition is released adds a new dimension. For simple sounds (i.e., pure
      tones), the off response can code a wide range of sound levels. For complex
      sounds, the off response becomes entrained to each modulation, resulting in a
      precise temporal coding of the envelope.

PMID- 10066279
TI  - The distribution of zinc selenite and expression of metallothionein-III mRNA in
      the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in
      sensory transmission.
AB  - Zinc appears to play a role in synaptic transmission in the hippocampus. We
      tested the hypothesis that zinc is similarly involved in sensory transmission by
      determining whether vesicular zinc and metallothionein-III (MT-III), a zinc
      binding protein, are localized in rat primary afferent neurons. MT-III mRNA,
      measured using RT-PCR, and MT-III immunoreactivity, were both present in the
      spinal cord as well as the thoracic and lumbar dorsal root ganglia (DRG). At a
      time (24 hr) that allows retrograde transport of zinc selenite to cell bodies,
      only small-diameter neurons and neurons scattered throughout lamina V of the
      spinal cord were stained by sodium selenite injected intrathecally. This stain
      disappeared if a ligature was placed on the dorsal root to block axonal
      transport, demonstrating that these cells are, in fact, zinc-containing primary
      afferent neurons. When assessed 1 hr after sodium selenite, stain was distributed
      throughout the neuropil of the spinal cord, especially in lamina III and the area
      surrounding the central canal. Even in rhizotomized animals, large- and small
      diameter DRG neuronal cell bodies were also stained with either selenite (1 hr)
      or 6-methoxy 8-para-toluene sulfonamide quinoline (TSQ). Paradoxically, this
      unique pool of zinc was eliminated in large-diameter DRG neurons after neonatal
      capsaicin treatment, which had no effect on selenite stain or MT-III mRNA content
      in small-diameter DRG neurons. In summary, we demonstrate that there is a
      population of capsaicin-insensitive small-diameter primary afferent neurons that
      are zinc-containing. In addition, there is a unique pool of capsaicin-sensitive
      zinc that is associated with large-diameter cell bodies.

PMID- 10066280
TI  - A glial cell line-derived neurotrophic factor-secreting clone of the Schwann cell
      line SCTM41 enhances survival and fiber outgrowth from embryonic nigral neurons
      grafted to the striatum and to the lesioned substantia nigra.
AB  - We have developed a novel Schwann cell line, SCTM41, derived from postnatal
      sciatic nerve cultures and have stably transfected a clone with a rat glial cell
      line-derived neurotrophic factor (GDNF) construct. Coculture with this GDNF
      secreting clone enhances in vitro survival and fiber growth of embryonic
      dopaminergic neurons. In the rat unilateral 6-OHDA lesion model of Parkinson's
      disease, we have therefore made cografts of these cells with embryonic day 14
      ventral mesencephalic grafts and assayed for effects on dopaminergic cell
      survival and process outgrowth. We show that cografts of GDNF-secreting Schwann
      cell lines improve the survival of intrastriatal embryonic dopaminergic neuronal
      grafts and improve neurite outgrowth into the host neuropil but have no
      additional effect on amphetamine-induced rotation. We next looked to see whether
      bridge grafts of GDNF-secreting SCTM41 cells would promote the growth of axons to
      their striatal targets from dopaminergic neurons implanted orthotopically into
      the 6-OHDA-lesioned substantia nigra. We show that such bridge grafts increase
      the survival of implanted embryonic dopaminergic neurons and promote the growth
      of axons through the grafts to the striatum.

PMID- 10066281
TI  - The superior olivary nucleus and its influence on nucleus laminaris: a source of
      inhibitory feedback for coincidence detection in the avian auditory brainstem.
AB  - Located in the ventrolateral region of the avian brainstem, the superior olivary
      nucleus (SON) receives inputs from nucleus angularis (NA) and nucleus laminaris
      (NL) and projects back to NA, NL, and nucleus magnocellularis (NM). The
      reciprocal connections between the SON and NL are of particular interest because
      they constitute a feedback circuit for coincidence detection. In the present
      study, the chick SON was investigated. In vivo tracing studies show that the SON
      projects predominantly to the ipsilateral NM, NL, and NA. In vitro whole-cell
      recording reveals single-cell morphology, firing properties, and postsynaptic
      responses. SON neurons are morphologically and physiologically suited for
      temporal integration; their firing patterns do not reflect the temporal structure
      of their excitatory inputs. Of most interest, direct stimulation of the SON
      evokes long-lasting inhibition in NL neurons. The inhibition blocks both
      intrinsic spike generation and orthodromically evoked activity in NL neurons and
      can be eliminated by bicuculline methiodide, a potent antagonist for GABAA
      receptor-mediated neurotransmission. These results strongly suggest that the SON
      provides GABAergic inhibitory feedback to laminaris neurons. We discuss a
      mechanism whereby SON-evoked GABAergic inhibition can influence the coding of
      interaural time differences for sound localization in the avian auditory
      brainstem.

PMID- 10066282
TI  - Early visual experience shapes the representation of auditory space in the
      forebrain gaze fields of the barn owl.
AB  - Auditory spatial information is processed in parallel forebrain and midbrain
      pathways. Sensory experience early in life has been shown to exert a powerful
      influence on the representation of auditory space in the midbrain space
      processing pathway. The goal of this study was to determine whether early
      experience also shapes the representation of auditory space in the forebrain.
      Owls were raised wearing prismatic spectacles that shifted the visual field in
      the horizontal plane. This manipulation altered the relationship between
      interaural time differences (ITDs), the principal cue used for azimuthal
      localization, and locations of auditory stimuli in the visual field.
      Extracellular recordings were used to characterize ITD tuning in the auditory
      archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and
      prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In
      prism-reared owls, unit tuning for ITD was shifted in the adaptive direction,
      according to the direction of the optical displacement imposed by the spectacles.
      Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD
      values and, to a lesser extent, the elimination of responses to nonadaptive
      (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to
      shifts in ITD tuning observed in the optic tectum of the same owls. This
      experience-based adjustment of binaural tuning in the AAr helps to maintain
      mutual registry between the forebrain and midbrain representations of auditory
      space and may help to ensure consistent behavioral responses to auditory stimuli.

PMID- 10066283
TI  - Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent
      morphological and behavioral abnormalities.
AB  - The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg)
      into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21,
      or into rat pups on postnatal day (P) 10. The principal findings were the
      following: (1) BrdU exposure on E11 produces profound effects on body morphology,
      and animals must be fed a special diet because of chronic tooth abnormalities;
      (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern,
      the precise pattern varying with age; (3) BrdU exposure on E15 or earlier
      produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or
      earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10
      reduces cerebellar size relative to cerebral size; (6) spatial learning is
      significantly affected after injections of BrdU at E11-E17, but the largest
      effect is on E17; (7) the deficit in spatial learning may be related in part to a
      reduction in visual acuity; and (8) skilled forelimb ability is most disrupted
      after BrdU exposure at E15 but is also impaired after injections on E13 or
      earlier. BrdU thus has teratological effects on body, brain, and behavior that
      vary with the developmental age of the fetus or infant.

PMID- 10066284
TI  - Presynaptic inhibition of GABA(B)-mediated synaptic potentials in the ventral
      tegmental area during morphine withdrawal.
AB  - Opioids increase the firing of dopamine cells in the ventral tegmental area by
      presynaptic inhibition of GABA release. This report describes an acute
      presynaptic inhibition of GABAB-mediated IPSPs by mu- and kappa-opioid receptors
      and the effects of withdrawal from chronic morphine treatment on the release of
      GABA at this synapse. In slices taken from morphine-treated guinea pigs after
      washing out the morphine (withdrawn slices), a low concentration of a mu receptor
      agonist increased, rather than decreased, the amplitude of the GABAB IPSP. In
      withdrawn slices, after blocking A1-adenosine receptors with 8-cyclopentyl-1, 3
      dipropylxantine, mu-opioid receptor activation inhibited the IPSP at all
      concentrations and increased the maximal inhibition. In addition, during
      withdrawal, there was a tonic increase in adenosine tone that was further
      increased by forskolin or D1-dopamine receptor activation, suggesting that
      metabolism of cAMP was the source of adenosine. The results indicate that during
      acute morphine withdrawal, there was an upregulation of the basal level of an
      opioid-sensitive adenylyl cyclase. Inhibition of this basal activity by opioids
      had two effects. First, a decrease in the formation of cAMP that decreased
      adenosine tone. This effect predominated at low mu receptor occupancy and
      increased the amplitude of the IPSP. Higher agonist concentrations inhibited
      transmitter release by both kinase-dependent and -independent pathways. This
      study indicates that the consequences of the morphine-induced upregulation of the
      cAMP cascade on synaptic transmission are dependent on the makeup of receptors
      and second messenger pathways present on any given terminal.

PMID- 10066285
TI  - Effect of chronic high-dose exogenous cortisol on hippocampal neuronal number in
      aged nonhuman primates.
AB  - Chronic exposure to increased glucocorticoid concentrations appears to lower the
      threshold for hippocampal neuronal degeneration in the old rat. It has been
      proposed that increased brain exposure to glucocorticoids may lower the threshold
      for hippocampal neuronal degeneration in human aging and Alzheimer's disease.
      Here, we asked whether chronic administration of high-dose cortisol to older
      nonhuman primates decreases hippocampal neuronal number as assessed by unbiased
      stereological counting methodology. Sixteen Macaca nemestrina (pigtailed
      macaques) from 18 to 29 years of age were age-, sex-, and weight-matched into
      pairs and randomized to receive either high-dose oral hydrocortisone (cortisol)
      acetate (4-6 mg/kg/d) or placebo in twice daily palatable treats for 12 months.
      Hypothalamic-pituitary-adrenal activity was monitored by measuring plasma
      adrenocorticotropin and cortisol, 24 hr urinary cortisol, and CSF cortisol.
      Urinary, plasma, and CSF cortisol were elevated, and plasma adrenocorticotropin
      was reduced in the active treatment group. Total hippocampal volume, subfield
      volumes, subfield neuronal density, and subfield total neuronal number did not
      differ between the experimental groups. These findings suggest that chronically
      elevated cortisol concentrations, in the absence of stress, do not produce
      hippocampal neuronal loss in nonhuman primates.

PMID- 10066286
TI  - Role of the CNS melanocortin system in the response to overfeeding.
AB  - The voluntary suppression of food intake that accompanies involuntary overfeeding
      is an effective regulatory response to positive energy balance. Because the pro
      opiomelanocortin (POMC)-derived melanocortin system in the hypothalamus promotes
      anorexia and weight loss and is an important mediator of energy regulation, we
      hypothesized that it may contribute to the hypophagic response to overfeeding.
      Two groups of rats were overfed to 105 and 116% of control body weight via a
      gastric catheter. In the first group, in situ hybridization was used to measure
      POMC gene expression in the rostral arcuate (ARC). Overfeeding increased POMC
      mRNA in the ARC by 180% relative to levels in control rats. For rats in the
      second group, the overfeeding was stopped, and they were infused
      intracerebroventricularly with SHU9119 (SHU), a melanocortin (MC) antagonist at
      the MC3 and MC4 receptor, or vehicle. Although SHU (0.1 nmol) had no effect on
      food intake of control rats, intake of overfed rats increased by 265% relative to
      CSF-treated controls. This complete reversal of regulatory hypophagia not only
      maintained but actually increased the already elevated weight of overfed rats,
      whereas CSF-treated overfed rats lost weight. These results indicate that CNS MCs
      mediate hypophagic signaling in response to involuntary overfeeding and support
      the hypothesis that MCs are important in the central control of energy
      homeostasis.

PMID- 10066287
TI  - Concurrent inhibition and excitation of phrenic motoneurons during inspiration:
      phase-specific control of excitability.
AB  - The movements that define behavior are controlled by motoneuron output, which
      depends on the excitability of motoneurons and the synaptic inputs they receive.
      Modulation of motoneuron excitability takes place over many time scales. To
      determine whether motoneuron excitability is specifically modulated during the
      active versus the quiescent phase of rhythmic behavior, we compared the input
      output properties of phrenic motoneurons (PMNs) during inspiratory and expiratory
      phases of respiration. In neonatal rat brainstem-spinal cord preparations that
      generate rhythmic respiratory motor outflow, we blocked excitatory inspiratory
      synaptic drive to PMNs and then examined their phase-dependent responses to
      superthreshold current pulses. Pulses during inspiration elicited fewer action
      potentials compared with identical pulses during expiration. This reduced
      excitability arose from an inspiratory-phase inhibitory input that hyperpolarized
      PMNs in the absence of excitatory inspiratory inputs. Local application of
      bicuculline blocked this inhibition as well as the difference between inspiratory
      and expiratory firing. Correspondingly, bicuculline locally applied to the
      midcervical spinal cord enhanced fourth cervical nerve (C4) inspiratory burst
      amplitude. Strychnine had no effect on C4 output. Nicotinic receptor antagonists
      neither potentiated C4 output nor blocked its potentiation by bicuculline,
      further indicating that the inhibition is not from recurrent inhibitory pathways.
      We conclude that it is bulbospinal in origin. These data demonstrate that rapid
      changes in motoneuron excitability occur during behavior and suggest that
      integration of overlapping, opposing synaptic inputs to motoneurons is important
      in controlling motor outflow. Modulation of phasic inhibition may represent a
      means for regulating the transfer function of PMNs to suit behavioral demands.

PMID- 10066288
TI  - Spatial- and task-dependent neuronal responses during real and virtual
      translocation in the monkey hippocampal formation.
AB  - Neuropsychological data in humans demonstrated a pivotal role of the medial
      temporal lobe, including the hippocampal formation (HF) and the parahippocampal
      gyrus (PH), in allocentric (environment-centered) spatial learning and memory. In
      the present study, the functional significance of the monkey HF and PH neurons in
      allocentric spatial processing was analyzed during performance of the spatial
      tasks. In the tasks, the monkey either freely moved to one of four reward areas
      in the experimental field by driving a cab that the monkey rode (real
      translocation task) or freely moved a pointer to one of four reward areas on the
      monitor (virtual translocation task) by manipulating a joystick. Of 389 neurons
      recorded from the monkey HF and PH, 166 had place fields that displayed increased
      activity in a specific area in the experimental field and/or on the monitor
      (location-differential neurons). More HF and PH neurons responded in the real
      translocation task. These neurons had low mean spontaneous firing rates (0.96
      spikes/sec), similar to those of rodent HF place cells. The remaining
      nonresponsive neurons had significantly higher mean firing rates (8. 39
      spikes/sec), similar to interneurons or theta cells in the rodent HF.
      Furthermore, most location-differential neurons showed different responses in
      different tasks. These results suggest that the HF and PH are crucial in
      allocentric information processing and, moreover, that the HF can encode
      different reference frames that are context or task-dependent. This may be the
      neural basis of episodic memory.

PMID- 10066289
TI  - Alteration of descending modulation of nociception during the course of
      monoarthritis in the rat.
AB  - Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures
      and modulate the transmission of nociceptive signals, were investigated at
      different stages during the development of adjuvant-induced monoarthritis in the
      rat. After behavioral evaluation, recordings of trigeminal convergent neurons
      were performed in anesthetized animals with acute (24-48 hr) or chronic (3-4
      weeks) monoarthritis of the ankle. Inhibitions of C-fiber-evoked neuronal
      responses during and after the application of noxious conditioning stimuli to the
      ankle were measured to evaluate DNIC. The conditioning stimuli consisted of
      mechanical (maximal flexion and graded pressures) and graded thermal stimuli and
      were applied alternately to normal and arthritic ankles. Behaviorally, the two
      groups of animals exhibited a similar increased sensitivity to mechanical stimuli
      applied to the arthritic joint (i.e., an increased ankle-bend score and a
      decreased vocalization threshold to pressure stimuli). However, they showed
      different electrophysiological profiles. In the animals with acute monoarthritis,
      the DNIC-induced inhibitions produced by mechanical or thermal stimulation of the
      arthritic joint were significantly increased at all intensities compared with the
      normal joint. In contrast, in the chronic stage of monoarthritis, the DNIC
      induced inhibitions triggered by thermal or pressure stimuli were similar for
      both ankles, except with the most intense mechanical stimuli. This discrepancy
      between the behavioral and electrophysiological findings suggests that inputs
      activated during chronic monoarthritis may fail to recruit DNIC and may thus be
      functionally different from those activated in the acute stage of inflammation.

PMID- 10066291
TI  - Searching for coronary disease among people with diabetes.

PMID- 10066290
TI  - Dissociation in effects of lesions of the nucleus accumbens core and shell on
      appetitive pavlovian approach behavior and the potentiation of conditioned
      reinforcement and locomotor activity by D-amphetamine.
AB  - Dopamine release within the nucleus accumbens (NAcc) has been associated with
      both the rewarding and locomotor-stimulant effects of abused drugs. The functions
      of the NAcc core and shell were investigated in mediating amphetamine-potentiated
      conditioned reinforcement and locomotion. Rats were initially trained to
      associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After
      excitotoxic lesions that selectively destroyed either the NAcc core or shell,
      animals underwent additional CS-US training sessions and then were tested for the
      acquisition of a new instrumental response that produced the CS acting as a
      conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine
      (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither
      Pavlovian nor instrumental conditioning but completely abolished the potentiative
      effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals
      were impaired during the Pavlovian retraining sessions but showed no deficit in
      the acquisition of responding with CR. However, the selectivity in stimulant
      induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine
      infusions dose-dependently increased responding on both the CR lever and a
      nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated
      amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity
      and enhanced the locomotor-stimulating effect of amphetamine. These results
      indicate a functional dissociation of subregions of the NAcc; the shell is a
      critical site for stimulant effects underlying the enhancement of responding with
      CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is
      implicated in mechanisms underlying the expression of CS-US associations.

PMID- 10066292
TI  - Antibiotics before dental work: who needs them?

PMID- 10066293
TI  - Apples and pears.

PMID- 10066294
TI  - Magic bullet or dietary machine gun?

PMID- 10066295
TI  - An herbal weight-loss drug fails in rigorous testing.

PMID- 10066296
TI  - Teen cholesterol levels dropping.

PMID- 10066297
TI  - I have aortic regurgitation (leaking of the aortic valve), and my physician says
      it is time to think about surgery. I feel pretty well - I can ski, play tennis.
      What do I have to lose by putting the surgery off?

PMID- 10066298
TI  - I am a 60 year-old woman and have a question about my cholesterol levels. My
      total cholesterol level is normal (just over 200) but my HDL is low, only 28.
      Should I be taking a cholesterol-lowering medicine?

PMID- 10066299
TI  - Getting relief. Your aching feet.

PMID- 10066300
TI  - Dysthymia. Treating mild depression's major effects.

PMID- 10066301
TI  - Essential tremor. Don't get shaken by this manageable disease.

PMID- 10066302
TI  - Prevention. A drink a day may protect against stroke.

PMID- 10066303
TI  - Ultrasound predicts coronary disease risk.

PMID- 10066304
TI  - Women and heart surgery.

PMID- 10066305
TI  - By the way, doctor... In your May issue you say that eating medium or well-done
      beef increases one's risk for stomach cancer. But what about the dangers of
      eating rare beef?

PMID- 10066311
TI  - Testicular cancer.

PMID- 10066313
TI  - It works: good nutrition prolongs life.

PMID- 10066312
TI  - Cigars and health: the National Cancer Institute reports.

PMID- 10066314
TI  - In-line skating: as good as running, as bad as biking.

PMID- 10066315
TI  - Body size and prostate cancer.

PMID- 10066316
TI  - My doctor always tells me my blood pressure readings, but the numbers confuse me.
      Can you please explain what they mean?

PMID- 10066317
TI  - More evidence for exercise.

PMID- 10066318
TI  - Aging. Alzheimer's disease.

PMID- 10066319
TI  - Advances in women's health.

PMID- 10066320
TI  - Breast cancer. Estrogen's long-term influence.

PMID- 10066321
TI  - Supplements for PMS.

PMID- 10066322
TI  - Evista and the brain.

PMID- 10066323
TI  - I had a hysterectomy and my ovaries were also removed in 1986, when I was 46.
      After combinations of estrogen in tablets and patches failed to relieve my hot
      flashes, my doctor tried monthly estrogen injections. They controlled my symptoms
      beautifully, and I have been taking them ever since. I have not been able to find
      much information about estrogen injections. is there any harm in taking the
      hormone this way?

PMID- 10066324
TI  - My insurance company won't pay for my prescription for Viagra without a letter
      from my doctor saying that I have been evaluated. As far as I know, I am the only
      one who can tell whether I have impotence. What does the insurance company want?

PMID- 10066326
TI  - I'm trying to reduce my cholesterol by eating foods that are low in fat. What
      exactly does it mean when a food item is labeled as "low-fat" or "light"?

PMID- 10066325
TI  - My husband has fainted two times in the last year. Both times, I took him to the
      hospital. The doctors watched him overnight and then sent him home, because his
      EKG was fine and they said that there was nothing wrong. What could be causing
      this problem? Should he have any more tests?

PMID- 10066327
TI  - Gay, lesbian and bisexual young people 

PMID- 10066328
TI  - Factors predicting continued violence into young adulthood.
AB  - The delinquent behaviour of a sample of 150 Dutch adolescent to young adult
      juveniles was examined. These juveniles were arrested because of status offences
      and delinquency. Arrested adolescent juveniles reported more delinquent behaviour
      than adolescents in the normal youth population. At the onset of adulthood the
      number of previously arrested youth reporting serious delinquent behaviour had
      substantially dropped. This developmental pattern is comparable to the pattern
      found in the general population of normal adolescents. It suggests that the
      delinquency of many arrested juveniles is largely adolescence-limited, similar to
      the delinquency of normal youth. However, about one-third of the arrested
      juveniles continued to engage in delinquent behaviour into young adulthood. A
      longitudinal analysis of factors predicting continued violence into adulthood
      revealed that serious delinquency during adolescence, as well as increased
      parental control and decreased parental support, were associated with increased
      delinquency in early adulthood.

PMID- 10066329
TI  - Exposure to violence, depression, and hostility in a sample of inner city high
      school youth.
AB  - This study examines the prevalence of violence in a non-randomly selected
      population of 337 inner city school students, the relationship between exposure
      to violence and symptoms of depression and hostility, and demographic differences
      in exposure to and effects of traumatic violence. Students responded to an
      anonymous survey asking them to enumerate how many times they had experienced
      each of six types of traumatic violence. Sixty-two per cent of students were
      exposed to an average of 3.0541 of the six types of violence listed. Exposure to
      most types of violence were highly intercorrelated. Males experienced more
      exposure to violence than females. Exposure to violence was predictive of
      hostility for both gender groups, and predictive of depression for females.
      Implications of exposure to traumatic violence on adolescent development are
      discussed.

PMID- 10066330
TI  - Adolescents' ideas of normative life span development and personal future goals.
AB  - We investigated how 57 adolescents (23 girls and 34 boys), aged 12 to 15 years,
      compared their idea of normative life span development to their personal future
      goals. A two-stage study (questionnaire and follow-up interview) included two
      open-ended "life paths", measures for self-evaluation and self-other comparisons.
      Overlap of content categories in the life paths supported the relationship
      between individual goals and normative expectations about life span development,
      especially when it comes to the life domains of education, occupation, family,
      property and retirement. The respondents showed an awareness of the accumulation
      of social problems, reporting that crises (e.g. alcoholism) and negative events
      (e.g. unemployment) are more likely to occur to the average adult than in their
      personal future. If adolescents rated their future as better than the future of
      others, they also regarded that future as different from the normative life span.
      Self-evaluation was indirectly related with self-other comparisons. Similarity
      between the normative life span and personal future correlated with higher
      probability of problem occurrence and possibility to avoid the problems.

PMID- 10066331
TI  - Love is all you need? Focusing on adolescents' life concerns from an ecological
      point of view.
AB  - Focal theory, in trying to explain why the majority of young people cope
      comparatively well with the variety of transitional tasks they are confronted
      with during adolescence, suggests that adolescents deal with only one issue at a
      time: concerns about heterosexual relationships peak around 11, concerns about
      peer acceptance around 15, and about relationship to and independence from
      parents at 15 for girls and 17 for boys. However, the model has been criticized
      for not taking into account economic problems and unemployment. The present study
      sets out to empirically test the implications of focal theory with a large
      Swedish sample of 1217 adolescents between 11 and 20 by means of a school-based
      questionnaire. Young people answered how often they worry about relationship,
      economic, global and other personal issues. Results show that focal theory should
      not be taken literally with regard to certain age-related sequences of problems.
      However, the main concept proposed by Coleman, i.e. that the number of problems
      dealt with has implications for adolescents' psychological well-being, is
      strongly supported by the data in this study. Finally, the notion that young
      people can choose how many issues they focus upon at a time is critically
      discussed.

PMID- 10066332
TI  - Relationships during adolescence: constructive vs. negative themes and relational
      dissatisfaction.
AB  - The present study set out to test Coleman's focal theory of adolescence in a
      cross-national context. The London Sentence Completion Test (LSCT) and the
      Louvain Loneliness Scale for Children and Adolescents (LLCA) were administered to
      370 adolescents (11 to 17 years of age) in the Dutch-speaking part of Belgium.
      The findings confirm those of earlier work using the London Sentence Completion
      Test (LSCT) and other questionnaire-type measures in various English-speaking
      countries (England, Scotland, New Zealand and United States). The general pattern
      of peak ages for adolescents' interpersonal concerns provided support for the
      focal model. Negative feelings about being alone, relationships with parents,
      heterosexual relationships, small groups and rejection from larger groups do not
      emerge all at once, but seem to be dealt with issue by issue. The results for the
      Louvain Loneliness Scale for Children and Adolescents (LLCA), which measures
      loneliness in relationships with both parents and peers, and adolescents'
      attitudes towards being alone, confirmed the age trends observed with the
      sentence completion measure. Taken together, these findings strongly suggest that
      the changes in adolescent relationships are intimately linked to the general
      process of individuation, as implied by the focal model. It should be pointed
      out, however, that important parts of the focal theory remain at present
      untested. Suggestions for future empirical and conceptual work related to these
      aspects of Coleman's model are outlined.

PMID- 10066333
TI  - Predisposing factors and consequences of occupational status for long-term
      unemployed youth: a longitudinal examination.
AB  - In a longitudinal study, long-term unemployed youth were assessed at T1 on
      measures of psychological health (self-esteem and psychological distress),
      general ability and literacy levels. At T2, three occupational groups were
      established (those employed at T2, those continuously unemployed between T1-T2
      and those unemployed at T2 who had been in the paid work force between T1-T2).
      These three groups were examined, first in relation to predisposing factors for
      occupational status, and second in relation to psychological health consequences
      of occupational status. Psychological health was not identified as a predictor of
      occupational status. Reductions in psychological distress occurred at T2 for the
      employed group only. No changes occurred in self-esteem for any group. General
      ability, literacy levels and length of unemployment were identified as
      predisposing factors for occupational status. Those with higher general ability,
      better literacy and shorter periods of unemployment at T1 were more likely to be
      employed at T2.

PMID- 10066334
TI  - Investigating the role of alienation in a multicomponent model of juvenile
      delinquency.
AB  - Research findings indicate that there are multiple causal pathways to
      delinquency. A multicomponent model of delinquency was developed to explore
      systematically the interrelationships of psychosocial variables and their
      relationships to delinquent behaviour. Most importantly, alienation was tested
      for its ability to act as a core mediating predictor variable. One hundred and
      fifty-two adolescents, 78 females and 74 males, completed a battery of
      questionnaires designed to assess each of the variables in the proposed model.
      Several salient pathways to delinquency were identified. They include
      environmental and person-centred factors. Alienation, when operationalized as a
      general construct, was not found to be a necessary mediating predictor variable.
      "Societal" alienation, on the other hand, was shown to have important explanatory
      power. Re-examining the model within a large-scale, time-extended study could
      inform programmes for the prevention and early intervention of delinquent
      behaviour.

PMID- 10066335
TI  - Social support, relationship quality, and well-being among pregnant adolescents.
AB  - This study examined the role of social support and relationship quality on the
      well-being of pregnant adolescents. Sixty-seven Black and 43 White single
      pregnant teens participated in the study. The reciprocal exchange of support
      between parents and teens was correlated with increased mastery and life
      satisfaction and decreased depression and anxiety. However, the reciprocal
      exchange of support with friends did not correlate with well-being. A high
      quality relationship with a significant other was associated with increased self
      esteem among pregnant teens dating the father of their child. This study extends
      the adolescent pregnancy literature by considering the reciprocal exchange of
      support and relationship quality with the partner.

PMID- 10066336
TI  - Associations between behavioural and emotional problems in adolescence and
      maladjustment in young adulthood.
AB  - This study was designed to investigate associations between emotional and
      behavioural problems in adolescence and psychopathology in young adulthood. Seven
      hundred and six 11- to 16-year-olds from the Dutch general population were
      followed across a period of 8 years and 8 months. Subjects were initially
      assessed using the Child Behaviour Checklist (CBCL). At follow-up, a subsample of
      131 subjects were assessed for DSM-III-R Axis 1 diagnoses with the SCAN (a semi
      structured interview), while the Global Assessment of Functioning scale and the
      Groningen Social Disabilities Schedule were used to assess functioning in daily
      life. Scores on the CBCL scales Withdrawn, Anxious/Depressed, Somatic Complaints,
      Social Problems and Thought Problems in adolescence were associated with DSM-III
      R symptomatology or dysfunctioning in young adulthood.

PMID- 10066337
TI  - Health status of juvenile offenders. A survey of young offenders appearing before
      the juvenile courts.
AB  - This paper reports on the health needs of a sample of juvenile offenders
      appearing before a Manchester Court during the month of August 1992. Of the 192
      subjects interviewed (74% of those listed), 19% had significant medical problems,
      42% a history of substance abuse and 7% psychiatric problems requiring further
      treatment. Substantial numbers (26%) engaged in a variety of dangerous
      behaviours. Custodial remands were common (21%), particularly in those with
      multiple psychosocial difficulties.

PMID- 10066338
TI  - Suicide among the young--the size of the problem.
AB  - It is widely recognized that official suicide rates conceal the real scale of non
      accidental self-injurious fatal behaviour, including among children and young
      people. There are many reasons for this including the constraints of registration
      policy and practice, uncertainty about the circumstances surrounding a death, an
      unwillingness-often for the family's sake-to affix a suicide label on a child,
      and perhaps the belief that the term "suicide" is not quite accurate. The present
      study examined all records over a 17-year period from an inner London coroner's
      office in order to make some quantitative assessment of the extent to which non
      accidental self-injurious deaths might be underestimated by suicide returns among
      those under 20 years. It is suggested on the basis of this examination that the
      real rate of what might be termed "suicide" among this group may be up to three
      times the official recorded level. This finding received general confirmation
      from a smaller-scale comparison in an out of London location.

PMID- 10066339
TI  - Pubertal timing and self-reported delinquency among male adolescents.
AB  - Pubertal timing has consequences for adolescent adaptation, and Moffitt has
      theorized that puberty is a motivating factor for delinquency. Pubertal timing
      and self-reported delinquency were examined in a questionnaire-based survey of 14
      year-old boys (n=99). The questionnaire was completed anonymously, under test
      conditions, in the school classroom. The results showed that offtime maturers
      (those early or late) reported a wider range of delinquency, including higher
      levels of crime and school opposition behaviours. Offtimers also reported a
      greater frequency of particular delinquent acts over a 12-month period. Overall,
      the results lend support to the "deviance hypothesis" of pubertal timing.

PMID- 10066341
TI  - Multidose streptozotocin induction of diabetes in BALB/cBy mice induces a T cell
      proliferation defect in thymocytes which is reversible by interleukin-4.
AB  - Thymic T cell function in streptozotocin-treated (STZ) diabetic mice has been
      examined. STZ administration suppresses thymic T cell proliferation in response
      to mitogen stimulation in vitro. Secretion of IL-4 was dramatically reduced;
      however, secretion of IL-2 or IFN-gamma was not significantly inhibited. RT-PCR
      analysis of thymocyte RNA revealed that levels of IL-4 mRNA were dramatically
      decreased in STZ-treated mice. Levels of mRNA encoding IFN-gamma were similar,
      but the appearance was delayed in thymocytes derived from STZ-treated mice,
      implying differential regulation of IL-4 and IFN-gamma. Defective thymocyte
      proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4
      completely reversed the STZ-induced defect. Administration in vivo of IL-4 before
      STZ treatment reversed the STZ-induced thymocyte proliferation defect and
      prevented both pancreatic islet destruction and hyperglycemia. Thymocyte cell
      surface differentiation markers were not appreciably different from control mice.
      Collectively these experiments suggest that STZ treatment of mice reduces
      expression of IL-4 which is associated with development of autoimmune diabetes.

PMID- 10066342
TI  - 4-1BB costimulation promotes human T cell adhesion to fibronectin.
AB  - CD28 and 4-1BB (CD137) are costimulatory molecules for T cells. In this study we
      investigated the role of 4-1BB in T cell adhesion to fibronectin (FN). Unlike
      CD28, 4-1BB is present in only a small subset of T cells prepared from fresh
      human peripheral blood mononuclear cells, but was induced after prolonged
      TCR/CD28 activation in vitro. 4-1BB-expressing T cells were characteristically
      unique in their strong responsiveness to FN. Anti-4-1BB cross-linking synergized
      CD28 costimulation by lowering the threshold of CD3 signal required for CD28
      mediated maximal proliferative response. In addition to increasing proliferative
      responses, 4-1BB promoted T cell adhesion to FN in the presence of CD28
      costimulation. 4-1BB-mediated cell adhesion to FN was blocked by anti-beta1
      integrin, suggesting that 4-1BB mediates beta1 integrin activation. The role of 4
      1BB in inducing CD4(+) T cell adhesion to FN was confirmed by showing that the
      human leukemic CD4(+) T cell line, Jurkat, when transfected with cDNA encoding 4
      1BB, became adherent to FN with anti-4-1BB stimulation. Taken together, our
      results suggest that 4-1BB-promoted T cell adhesion to extracellular matrix
      proteins is an important postactivation process for T cell migration.

PMID- 10066343
TI  - IFN-gamma-dependent nitric oxide production is not linked to resistance in
      experimental African trypanosomiasis.
AB  - Resistance to African trypanosomes is dependent on B cell and Th1 cell responses
      to the variant surface glycoprotein (VSG). While B cell responses to VSG control
      levels of parasitemia, the cytokine responses of Th1 cells to VSG appear to be
      linked to the control of parasites in extravascular tissues. We have recently
      shown that IFN-gamma knockout (IFN-gamma KO) mice are highly susceptible to
      infection and have reduced levels of macrophage activation compared to the wild
      type C57BL/6 (WT) parent strain, even though parasitemias were controlled by VSG
      specific antibody responses in both strains. In the present work, we examine the
      role of IFN-gamma in the induction of nitric oxide (NO) production and host
      resistance and in the development of suppressor macrophage activity in mice
      infected with Trypanosoma brucei rhodesiense. In contrast to WT mice, susceptible
      IFN-gamma KO mice did not produce NO during infection and did not develop
      suppressor macrophage activity, suggesting that NO might be linked to resistance
      but that suppressor cell activity was not associated with resistance or
      susceptibility to trypanosome infection. To further examine the consequence of
      inducible NO production in infection, we monitored survival, parasitemia, and Th
      cell cytokine production in iNOS KO mice. While survival times and parasitemia of
      iNOS KO mice did not differ significantly from WT mice, VSG-specific Th1 cells
      from iNOS KO mice produced higher levels of IFN-gamma and IL-2 than cells from WT
      mice. Together, these results show for the first time that inducible NO
      production is not the central defect associated with susceptibility of IFN-gamma
      KO mice to African trypanosomes, that IFNgamma-induced factors other than iNOS
      may be important for resistance to the trypanosomes, and that suppressor
      macrophage activity is not linked to either the resistance or the susceptibility
      phenotypes.

PMID- 10066344
TI  - The adenosine deaminase-binding region is distinct from major anti-CD26 mAb
      epitopes on the human dipeptidyl peptidase IV(CD26) molecule.
AB  - CD26 or dipeptidyl peptidase IV (DPP-IV) is a cell surface protease involved in T
      cell activation. Monoclonal antibodies (mAbs) directed against the CD26 molecule
      are able to stimulate CD26-expressing T cells. Although many different CD26
      specific mAbs exist which are able to provide a triggering signal in T cells,
      little is known about their specific epitopes on the CD26 molecule. Whereas some
      mAbs were shown to compete with each other and to inhibit the association of
      adenosine deaminase (ADA) and human immunodeficiency virus 1 (HIV-1)-derived Tat
      protein with CD26, other CD26-specific mAbs obviously bind to distinct regions on
      DPP-IV. In the present study we have generated truncated versions of the human
      CD26 molecule and expressed them in COS-1 cells to study the binding pattern of a
      panel of 14 CD26-specific mAbs in confocal microscopy and, thus, correlated the
      CD26-specific mAbs epitopes with the binding region of ADA. We show that the
      majority of anti-CD26 mAbs is directed against the glycosylation-rich region of
      the molecule whereas the ADA-binding site could be located in the cysteine-rich
      region of DPP-IV. In contrast to binding experiments with purified ADA, which
      revealed a specific association with CD26 on CD26-positive Jurkat cells, HIV
      derived Tat protein did not interact specifically with CD26 on transfected Jurkat
      cells, nor could Tat binding be competed by anti-CD26-specific mAbs.

PMID- 10066345
TI  - The regulatory effects of all-trans-retinoic acid on isotype switching: retinoic
      acid induces IgA switch rearrangement in cooperation with IL-5 and inhibits IgG1
      switching.
AB  - All-trans-retinoic acid (RA) can induce germline Calpha transcription in LPS
      stimulated murine mu(+)B-cells by a TGF-beta-independent mechanism. In the
      present study, we examined whether RA can further drive the IgA switching process
      to Smu-Salpha switch rearrangement by DC-PCR. RA alone could not induce switch
      rearrangement but required the cooperation of IL-5. RA has another effect on
      isotype switching; RA strongly inhibits IL-4-dependent IgG1 and IgE production.
      To analyze the mechanism of IgG1 inhibition, we tested whether RA can inhibit IL
      4-dependent Smu-Sgamma1 switch rearrangement. IL-4 by itself could induce Smu
      Sgamma1 switch rearrangement in LPS-stimulated mu(+)B-cells. Addition of RA
      inhibited this reaction. RA also showed an inhibitory effect on the preceding
      step, i.e., Igamma1Cgamma1 transcription. Therefore, RA inhibition of Smu-Sgamma1
      switch rearrangement was regulated at the level of germline Cgamma1
      transcription. We further analyzed the amounts of both Igamma1Cgamma1 and
      IalphaCalpha expressed in LPS-stimulated B-cells exposed to mixtures of the two
      switch inducers, RA and IL-4, at various concentrations and found that the two
      transcripts were regulated antagonistically. These results indicated that RA can
      regulate isotype switching at the level of germline transcription and directs
      switching to IgA with the help of IL-5 and inhibits IgG1 switching.

PMID- 10066346
TI  - Effects of cigarette smoking on Fas/Fas ligand expression of human lymphocytes.
AB  - Cigarette smoking has been shown to affect human immune responses. We have
      studied Fas/Fas ligand (FasL) expression, which is involved in the cytotoxic
      activity, immune privilege, and self-tolerance, and other apoptosis-associated
      molecule expression of peripheral blood lymphocytes (PBL) in healthy subjects
      with/without cigarette smoking. We found that expression of FasL protein was
      detected marginally in the fresh PBL and was induced upon mitogen activation in
      normal individuals without smoking. In contrast, fresh PBL from those with
      chronic cigarette smoking exhibited enhanced expression of FasL protein without
      in vitro mitogen stimulation. Moreover, mitogen stimulation failed to augment
      FasL protein expression of their lymphocytes, suggesting dysregulation of FasL
      expression of PBL in individuals with cigarette smoking. In contrast, Fas, Bcl-2,
      and p53 expression were not significantly different between normal individuals
      with chronic cigarette smoking and those without smoking. In addition, we found
      that in vitro brief treatment with nicotine induces and/or enhances FasL mRNA and
      protein expression of lymphocytes from normal donors without smoking. These
      results suggest that aberrant FasL expression of lymphocytes is, at least in
      part, involved in the immune impairment in individuals with chronic cigarette
      smoking.

PMID- 10066347
TI  - A divalent major histocompatibility complex/IgG1 fusion protein induces antigen
      specific T cell activation in vitro and in vivo.
AB  - Activation of antigen-specific T cell clones in vivo might be possible by
      generating soluble MHC molecules; however, such molecules do not induce effective
      T cell responses unless cross-linked. As a first step in generating a soluble MHC
      molecule that could function as an antigen-specific immunostimulant, the
      extracellular domains of the murine H-2Kb MHC class I molecule were fused to the
      constant domains of a murine IgG1 heavy chain, resulting in a divalent molecule
      with both a TCR-reactive and an Fc receptor (FcR)-reactive moiety. The fusion
      protein can be loaded with peptide and can induce T cell activation in a peptide
      specific, MHC-restricted manner following immobilization on plastic wells or
      following cross-linking by FcR+ spleen cells. The fusion protein induces partial
      T cell activation in vivo in a mouse transgenic for a TCR restricted to H-2Kb.
      This fusion protein molecule may be useful to study peptide-MHC interactions and
      may provide a strategy for boosting in vivo antigen-specific T cell responses,
      such as to viral or tumor antigens.

PMID- 10066348
TI  - Differential expression and costimulatory effect of 4-1BB (CD137) and CD28
      molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells.
AB  - In this study we report that the relative expression of 4-1BB (CD137) and CD28
      molecules can differentially be modulated on CD8(+) T cells by combinations of
      various cytokines and anti-cytokine antibodies. During allostimulation of naive
      CD8(+) T cells in the presence of IL-2, IFN-gamma, IL-12, and anti-IL-4, they
      evolved into IL-2, IFN-gamma-producing Tc1 cells and showed inability to
      upregulate 4-1BB expression but not CD28. On the other hand, the Tc2 cells,
      generated in the presence of allogeneic APCs, IL-2, IL-10, IL-4, and anti-IFN
      gamma, demonstrated intact and elevated 4-1BB and CD28 molecules. Activation of
      Tc1 and Tc2 cells with anti-CD3 and plate-bound anti-4-1BB and anti-CD28 mAbs
      revealed differential proliferative and cytokine secretory patterns. The 4-1BB
      signaling in the context of anti-CD3 as first signal led to the increased
      secretion of IL-4 by the Tc2 cells and not by Tc1 cells, while CD28 triggering
      produced IL-4 from Tc2 and IL-2 and IFN-gamma from Tc1 cells. Flow cytometric
      analysis of cell surface expression on Tc1 and Tc2 cells strengthened our
      observation that 4-1BB expression but not CD28 is poorly expressed on Tc1 cells.
      Both of the polarized CD8(+) T cell subsets exhibited comparable cytotoxic
      abilities and perforin and granzyme expression. The regeneration of 4-1BB
      expression is possible on Tc1 cells when back cultured in a Tc2 cytokine
      environment, but its expression could not be significantly altered on the Tc2
      population unless IL-12 was included in the system.

PMID- 10066349
TI  - Induction of systemic Th1 and Th2 immune responses by oral administration of
      soluble antigen and diesel exhaust particles.
AB  - The present study was undertaken to examine whether oral administration of
      soluble antigen together with diesel exhaust particles (DEP) induced the systemic
      immune response in mice. Mice were orally given 1 mg of hen egg lysozyme (HEL)
      with varying doses of DEP every 3 days over a period of 15 days. The results
      showed that oral administration of HEL plus DEP produced anti-HEL IgG antibodies
      in serum in a dose-related fashion, while either HEL or DEP alone failed to show
      the antigen-specific IgG antibody production. Production of anti-HEL IgG2a and
      IgG1 antibodies, which are dependent on Th1 and Th2 CD4(+) T cells, respectively,
      was seen in mice fed with combined HEL and DEP, although anti-HEL IgG1 antibodies
      appeared to be more efficiently produced by lower doses of DEP than anti-HEL
      IgG2a antibodies. There was marked antigen-specific proliferation of spleen cells
      in mice treated with HEL and DEP. The anti-HEL antibody production and lymphoid
      cell proliferation to the antigen were associated with marked secretion of the
      Th1 cytokine IFN-gamma as well as the Th2 cytokine IL-4. These results suggest
      that DEP may act as a mucosal adjuvant in the gut enhancing systemic Th1 and Th2
      immune responses and might play a role in oral immunization and food allergy.

PMID- 10066350
TI  - Triggering HLA-DR molecules on human peripheral monocytes induces their death.
AB  - Although engagement of MHC class II molecules on human monocytes triggers various
      cellular events, their possible role in monocyte death is yet unknown. We
      demonstrate that ligation of MHC class II on primary monocytes induces a rapid
      cell death that has all the characteristics of monocyte apoptosis, does not
      require de novo protein synthesis, is independent from both Fas and TNF-alpha
      systems, and is not rescued by ligation of CD40. However, cell-cell interactions
      that involve the beta2-integrin CD18 seem to be critical for the execution of
      this monocyte death. Priming monocytes with IFN-gamma enhances significantly
      their HLA-DR-mediated death whereas LPS treatment effectively reverses this death
      process. Thus, our results describe the MHC class II molecules, in particular HLA
      DR, as mediators of monocyte death and suggest that this novel pathway of
      monocyte death might have an important role in controlling the outcome of
      inflammatory process and the regulation of monocyte hemostasis.

PMID- 10066352
TI  - Similarity measurement method for the classification of architecturally
      differentiated images.
AB  - A similarity measurement method for the classification of architecturally
      differentiated image sections is described. The strength of the method is
      demonstrated by performing the complex task of assigning severity grading
      (Gleason grading) to histological slides of prostate cancer. As shown, all that
      is required to employ the method is a small set of preclassified images. The
      images can be real world images acquired by means of a camera, computer
      tomography, etc., or schematic drawings representing samples of different
      classes. The schematic option allows a quick test of the method for a particular
      classification problem.

PMID- 10066353
TI  - The MISCAN-COLON simulation model for the evaluation of colorectal cancer
      screening.
AB  - A general model for evaluation of colorectal cancer screening has been
      implemented in the microsimulation program MISCAN-COLON. A large number of
      fictitious individual life histories are simulated in each of which several
      colorectal lesions can emerge. Next, screening for colorectal cancer is
      simulated, which will change some of the life histories. The demographic
      characteristics, the epidemiology and natural history of the disease, and the
      characteristics of screening are defined in the input. All kinds of assumptions
      on the natural history of colorectal cancer and screening and surveillance
      strategies can easily be incorporated in the model. MISCAN-COLON gives detailed
      output of incidence, prevalence and mortality, and the results and effects of
      screening. It can be used to test hypotheses about the natural history of
      colorectal cancer, such as the duration of progressive adenomas, and screening
      characteristics, such as sensitivity of tests, against empirical data. In
      decision making about screening, the model can be used for evaluation of
      screening policies, and for choosing between competing policies by comparing
      their simulated incremental costs and effectiveness outcomes.

PMID- 10066354
TI  - Classification of nasal inspiratory flow shapes by attributed finite automata.
AB  - In a significant proportion of individuals, the physiologic decrease of muscle
      tone during sleep results in increased collapsibility of the upper respiratory
      airway. At peak inspiratory flow, the pharyngeal soft tissues may collapse and
      cause airflow limitation or even complete occlusion of the upper airway (sleep
      apnea). While there are plenty of methods to detect sleep apnea, only a few can
      be used to monitor flow limitation in sleeping individuals. Nasal prongs
      connected to pressure sensor provide information of the nasal airflow over time.
      This paper documents a method to automatically classify each nasal inspiratory
      pressure profile into one without flow limitation or six flow-limited ones. The
      recognition of the sample signals consists of three phases: preprocessing,
      primitive extraction, and word parsing phases. In the last one, a sequence of
      signal primitives is treated as a word and we test its membership in the
      attribute grammars constructed to the signal categories. The method gave in
      practical tests surprisingly high performance. Classifying 94;pc of the
      inspiratory profiles in agreement with the visual judgment of an expert
      physician, the performance of the method was considered good enough to warrant
      further testing in well-defined patient populations to determine the pressure
      profile distributions of different subject classes.

PMID- 10066355
TI  - A novel algorithm for the heart rate variability analysis of short-term
      recordings: polar representation of respiratory sinus arrhythmia.
AB  - A new method for the analysis of heart rate variability in short-term recordings
      is presented which consists of an analysis of the respiratory sinus arrhythmia in
      the time domain by means of a polar representation. Its main advantage is that it
      is applicable in experiments in which the respiration of the subject is not
      controlled. The algorithm is applied to data recorded on two astronauts during
      the Euromir-95 space mission. Statistical hypothesis tests demonstrate that the
      presence of a mouthpiece induces an increase of the respiratory sinus arrhythmia
      amplitude.

PMID- 10066356
TI  - A health information network for managing innercity tuberculosis: bridging
      clinical care, public health, and home care.
AB  - The purpose of this study was to use a health information network and innovative
      technology to coordinate tuberculosis care. An innercity medical center, a local
      health department, and a home care nurse service in northern Manhattan were used.
      The organizations were linked with computer networks. An automated decision
      support system with a natural language processor was used to detect tuberculosis
      cases and report them to the health department, and to select patients for
      respiratory isolation. Educational materials were placed on the World Wide Web
      and a Web-based kiosk. Home care nurses were outfitted with wireless pen-based
      computers, and data were relayed to the medical center. Automated tuberculosis
      case reporting resulted in time savings but not improved accuracy. Automated
      rules resulted in significant improvements in respiratory isolation. Kiosk
      educational materials were well-used. Wireless computing led to better access to
      information for both nurses and physicians, but not to reduction of workload. The
      key success element was recognition of critical priorities. It is concluded that
      innovative technology can facilitate the coordination of clinical care, public
      health, and home care.

PMID- 10066357
TI  - Design of a PC-based system for time-domain and spectral analysis of heart rate
      variability.
AB  - Investigation of heart rate variability is the subject of considerable interest
      in physiology, clinical medicine, and clinical pharmacology. The functional
      assessment of the autonomic nerve system by observation of its main actors, the
      sympathetic and parasympathetic branch, is emphasizing the importance of
      autonomic regulation under different physiological circumstances, in several
      disease states, and under drug therapy. This paper describes a PC-based system
      designed with LabView that performs time-domain and frequency-domain analyses of
      heart rate variability as suggested by the guidelines of the European Society of
      Cardiology and the North American Society of Pacing and Electrophysiology.
      Examples for heart rate variability are given for different physiological states
      along with an analysis and evaluation by the system described.

PMID- 10066358
TI  - Disappearance of a novel protein component of the 26S proteasome during Xenopus
      oocyte maturation.
AB  - We have prepared polyclonal antibodies against Xenopus 20S proteasomes. The
      antibodies cross-react with several proteins that are common to 20S and 26S
      proteasomes and with at least two proteins that are unique to 26S proteasomes.
      The antibodies were used to analyze changes in the components of proteasomes
      during oocyte maturation and early development of Xenopus laevis. A novel protein
      with a molecular weight of 48 kDa, p48, was clearly detected in immature oocytes,
      but was found at very low levels in mature oocytes and ovulated eggs. p48 was
      reduced to low levels during oocyte maturation, after maturation-promoting factor
      was activated. The amount of p48 in eggs remained low during early embryonic
      development, but increased again after the midblastula transition. These results
      show that at least one component of 26S proteasomes changes during oocyte
      maturation and early development and suggest that alterations in proteasome
      function may be important for the regulation of developmental events, such as the
      rapid cell cycles, of the early embryo.

PMID- 10066359
TI  - Rapid and reversible regulation of collagen XII expression by changes in tensile
      stress.
AB  - We studied the expression of the fibril-associated collagen XII by fibroblasts
      cultured on attached (stretched) or floating (relaxed) collagen I gels.
      Accumulation of collagen XII in the medium as determined by semiquantitative
      immunoblotting was 8-16 times higher under stretched compared to relaxed
      conditions. Northern blot experiments showed that tensile stress controls
      collagen XII expression at the mRNA level. Tenascin-C mRNA levels were also
      influenced, whereas relative amounts of fibronectin and matrix metalloproteinase
      2 mRNA were barely affected. The response to a change in tensile stress is rapid,
      since de novo biosynthesis of collagen XII was fully down-regulated 12 h after
      relaxation of a stretched culture. To demonstrate that the effect is also
      reversible, we mounted collagen gels with attached cells to movable polyethylene
      plugs. The cultures were relaxed or stretched at intervals of 24 and 48 h, and
      media samples were analyzed every 24 h. By ELISA, the amount of collagen XII
      secreted into the medium was found to increase or decrease in accordance with the
      tensile stress applied. This is evidence that the mechanical stimulus per se,
      rather than an indirect secondary effect, was responsible for the observed
      changes in collagen XII production.

PMID- 10066360
TI  - Involvement of gicerin, a cell adhesion molecule, in development and regeneration
      of oviduct and metastasis of oviductal adenocarcinomas of the chicken.
AB  - Gicerin is a novel cell adhesion molecule in the immunoglobulin superfamily and
      has both homophilic adhesion and heterophilic adhesive activity to neurite
      outgrowth factor (NOF), an extracellular matrix protein in the laminin family. We
      investigated the possible involvement of gicerin in oviductal development,
      regeneration, and metastasis of oviductal adenocarcinomas of the chicken. In the
      oviductal epithelium, gicerin was expressed strongly during development,
      disappeared after maturation, and reappeared during regeneration. NOF was
      constitutively expressed in the basement membrane of the epithelium. These
      molecules were expressed strongly in oviductal adenocarcinomas in both primary
      and metastatic lesions in the mesentery. An anti-gicerin antibody inhibited the
      attachment of adenocarcinoma cells to the mesentery in vitro. Many cells migrated
      from adenocarcinoma tissues on NOF, which were inhibited by an anti-gicerin
      antibody. These results suggest that gicerin might play a role in oviductal
      development and regeneration and also in the metastasis of adenocarcinomas.

PMID- 10066361
TI  - Hormonal control of "tissue" transglutaminase induction during programmed cell
      death in frog liver.
AB  - In this study, we show that sex hormones (testosterone, estradiol, and
      progesterone) act as physiological modulators of programmed cell death (PCD)
      during the frog liver involution observed postvitellogenesis. PCD in parenchymal
      cells is paralleled by the specific induction of the "tissue" transglutaminase
      (tTG) gene. tTG protein specifically accumulates in hepatocytes showing the
      morphological features of apoptosis. The hormone-dependent increase of both PCD
      and tTG was reproduced in ovariectomized frogs. Treatment of castrated animals
      with testosterone, estradiol, and progesterone inhibited the induction of both
      tTG and PCD, thus indicating that in vivo the drop in the circulating sex hormone
      is the signal favoring the involution phase of the maternal frog liver after
      mating. Although an affinity-purified polyclonal antibody raised against
      mammalian transglutaminase reacts in frog liver with a 55- to 60-kDa protein,
      concomitant with the onset of PCD, tTG cleavage products were detected,
      suggesting a proteolytic processing of the enzyme protein. These results
      represent the first evidence indicating that the physiological involution
      occurring postvitellogenesis of frog liver takes place by programmed cell death
      and that this, together with the concomitant induction of tTG gene expression, is
      regulated by sex hormones.

PMID- 10066362
TI  - Id4 expression induces apoptosis in astrocytic cultures and is down-regulated by
      activation of the cAMP-dependent signal transduction pathway.
AB  - The Id family of helix-loop-helix transcription factors has been implicated in
      the regulation of cellular differentiation in several different lineages. We have
      explored the potential regulatory role of the cyclic AMP-dependent signaling
      pathway on Id gene expression in astroglial primary cultures. We found that
      primary cultures of mouse forebrain astrocytes constitutively expressed the four
      known members of the Id gene family, Id1, Id2, Id3, and Id4. During culture in
      presence of serum for 4 weeks, the expression of Id4 was up-regulated. In these
      same cultures, treatment with dibutyryl-cyclic AMP, a cyclic AMP analogue known
      to promote astrocyte differentiation, dramatically and selectively decreased Id4
      gene expression. This effect was detectable after short-term treatment and was
      maintained during long-term treatment. Forskolin and pentoxifylline, two other
      agents known to elevate intracellular cyclic AMP through different mechanisms,
      also potently decreased Id4 gene expression. Furthermore, overexpression of Id4
      in an astrocyte-derived cell line induced cells to round up and die by apoptosis.
      These results indicate that the cyclic AMP pathway acts as an inhibitor of Id4
      gene expression in astrocytes, identify a new function for Id4, and suggest that
      Id4 is strategically positioned in the chain of molecular events regulating
      astrocyte differentiation and apoptosis.

PMID- 10066363
TI  - A mutation that separates the RasG signals that regulate development and
      cytoskeletal function in Dictyostelium.
AB  - The expression of an activated RasG, RasG-G12T, in vegetative cells of
      Dictyostelium discoideium produced an alteration in cell morphology. Cells
      underwent a transition between an extensively flattened form that exhibited
      lateral membrane ruffling to a less flattened form that exhibited prominent
      dorsal membrane ruffling. These rasG-G12T transformants exhibited a
      redistribution of F-actin at the cell periphery and did not undergo the rapid
      contraction upon refeeding that is characteristic of wild-type cells. These
      results suggest a role for RasG in regulating cytoskeletal rearrangement in D.
      discoideum. We had shown previously that expression of rasG-G12T inhibited
      starvation induced aggregation (M. Khosla et al., 1996, Mol. Cell. Biol. 16, 4156
      4162). rasG-G12T genes containing secondary mutations were transformed into cells
      to test whether the effects of rasG-G12T were transmitted through a single
      downstream effector. Cells expressing rasG-G12T/T35S or rasG-G12T/Y40C (secondary
      mutations within the effector domain) exhibited normal morphology and underwent
      normal aggregation, suggesting that signaling through the effector domain was
      required for both the morphological and the development changes induced by rasG
      G12T. In contrast, cells expressing rasG-G12T/T45Q (a secondary mutation in the
      effector distal flanking domain) exhibited normal aggregation but a morphology
      indistinguishable from that of rasG-G12T transformants. This result suggests that
      RasG regulates developmental and cytoskeletal functions by direct interaction
      with more than one downstream effector.

PMID- 10066364
TI  - Regulation of tissue-type plasminogen activator and its inhibitor (PAI-1) by
      lipopolysaccharide-induced phagocytosis in a Sertoli cell line.
AB  - The plasminogen activator (PA) system is thought to play a major role in the
      proteolytic events associated with spermatogenesis. The mechanisms controlling
      the expression of PA and of its major physiological inhibitor, plasminogen
      activator inhibitor type-1 (PAI-1), in the seminiferous epithelium are still
      unknown. In the present study we analyzed the expression of PA and PAI-1 in a
      murine Sertoli cell line (42GPA9) in response to stimulation by
      lipopolysaccharides (LPS) used to activate the phagocytic activity of these
      cells. Immortalized Sertoli cells cultured under basal conditions secreted
      predominantly tissue-type PA (tPA) as demonstrated by zymographic analysis and
      the presence of tPA transcripts. In zymographic experiments a larger molecular
      weight proteolytic band corresponding to the formation of PA-PAI-1 complex was
      also observed. The stimulation of immortalized Sertoli cells by LPS resulted in
      both alteration of the apparent tPA molecular weight to a higher form and
      transient increase in PAI-1 biosynthesis. The phorbol ester TPA stimulates
      similarly PAI-1 synthesis in the Sertoli cell line, while 8-bromo-cAMP has no
      effect. These results suggest for the first time the existence of a direct
      linkage between molecular events triggered by phagocytosis and regulation of tPA
      and PAI-1 in Sertoli cells.

PMID- 10066365
TI  - Illegitimate expression of apolipoprotein A-II in Caco-2 cells is due to
      chromatin organization.
AB  - Transcriptional activity of the human apolipoprotein (apo) A-II promoter has been
      reported in transiently transfected Caco-2 cells, but not in the intestine in
      vivo. In the present study we established that the transcription of a stably
      transfected reporter gene under the control of the -911/+29 human apo A-II,
      decreases with the onset of the differentiation process. This decrease paralleled
      that of the expression of the endogenous apo A-II gene. The decrease in apo A-II
      expression is also followed by a marked increase in the expression of the
      intestine-specific apo A-IV gene, analyzed here as a marker of enterocytic
      differentiation. Using clonal glucose metabolic variants of Caco-2 cells we have
      also observed that the lowest levels of apo A-II mRNA are associated with the
      lowest rates of glucose consumption. The illegitimate apo A-II transcriptional
      activity observed in Caco-2 cells is linked to the presence of DNase-I
      hypersensitive sites within the enhancer. This reflects a chromatin organization
      which allows, in Caco-2 cells as in the liver, the communication between the apo
      A-II enhancer and the proximal promoter, unlike what is observed in intestinal
      epithelial cells.

PMID- 10066366
TI  - Caveolin is an inhibitor of platelet-derived growth factor receptor signaling.
AB  - Caveolin is a major structural component of caveolae and has been implicated in
      the regulation of the function of several caveolae-associated signaling
      molecules. Platelet-derived growth factor (PDGF) receptors and caveolin were
      colocalized in the same subcellular fraction after sucrose density gradient
      fractionation of fibroblasts. Additionally, we found that the PDGF receptors
      interacted with caveolin in NIH3T3 fibroblast cells. We then examined whether
      caveolin directly binds to PDGF receptors and inhibits kinase activity using a
      recombinant PDGF receptor overexpressed in insect cells and peptides derived from
      the scaffolding domain of caveolin subtypes. We found the peptide from caveolin-1
      and -3, but not -2, inhibited the autophosphorylation of PDGF receptors in a dose
      dependent manner. Similarly, caveolin-1 and -3 peptides directly bound to PDGF
      receptors. Mutational analysis using a series of truncated caveolin-3 peptides
      (20-, 17-, 14-, and 11-mer peptides) revealed that at least 17 amino acid
      residues of the peptide were required to inhibit and directly bind to PDGF
      receptors. Thus, our findings suggest that PDGF receptors directly interact with
      caveolin subtypes, leading to the inhibition of kinase activity. Caveolin may be
      another regulating factor of PDGF-mediated tyrosine kinase signaling.

PMID- 10066367
TI  - Mapping and characterization of the functional domains of the nucleolar protein
      RNA helicase II/Gu.
AB  - RNA helicase II/Gu (RH-II/Gu) is a nucleolar RNA helicase of the DEAD-box
      superfamily. In this study, the functional domains of RH-II/Gu molecule were
      mapped by fusing the protein or its deletion mutants with a green fluorescence
      protein and subsequently transfecting or microinjecting the recombinant
      constructs into HeLa cells. In addition to the identification of a nuclear
      localization signal (NLS) in the N-terminus and a nucleolar targeting signal in
      the central helicase domain, a hidden NLS and a nucleolar targeting signal were
      found in the C-terminal arginine/glycine-rich domain. RH-II/Gu colocalized with
      fibrillarin, a component of the dense fibrillar region of the nucleolus.
      Overexpression of the entire RH-II/Gu protein or specific domains of the protein
      in HeLa cells did not interfere with the normal distribution of fibrillarin.
      However, when the helicase domain was truncated, the distribution pattern of
      fibrillarin was distorted. Microinjection of the wild-type RH-II/Gu cDNA into the
      nucleus of HeLa cells did not disrupt normal cell growth. However, when cells
      were injected with mutant DNA, only a small percentage of HeLa cells progressed
      through the cell cycle. Analysis of centrosomes in transfected cells demonstrated
      that most of the mutant-expressing cells were arrested early in the cell cycle.
      The results suggest that each of the structural domains of RH-II/Gu is necessary
      for cell growth and cell cycle progression.

PMID- 10066368
TI  - Adipocyte-epithelial interactions regulate the in vitro development of normal
      mammary epithelial cells.
AB  - Mammary epithelial organoids (MEO), isolated from pubescent rats, were cultured
      within a reconstituted basement membrane in transwell inserts, in the presence or
      absence of mature mammary adipocytes in the lower well. This system allowed for
      free medium exchange between the two compartments, without direct cell-to-cell
      contact. When cultured in serum-free medium supplemented with insulin, prolactin,
      hydrocortisone, progesterone, and various epidermal growth factor (EGF)
      concentrations, mammary adipocytes did not affect epithelial cell growth, but
      enhanced epithelial differentiation. Casein and lipid accumulations were
      monitored as indicators of functional differentiation of MEO. Mammary adipocytes
      significantly enhanced casein and lipid accumulation within the MEO,
      independently of EGF concentration. Furthermore, adipocytes induced MEO to
      preferentially undergo alveolar morphogenesis, inhibited squamous outgrowth, and
      increased lumen size. These findings demonstrate that morphological and
      functional differentiation of mammary epithelial cells is profoundly enhanced by
      the adipose stroma and that these effects are mediated by diffusible paracrine
      factors. This new model can be exploited in future studies to define the
      mechanisms whereby hormones and growth factors regulate mammary gland development
      and carcinogenesis. Moreover, it could complement in vivo
      reconstitution/transplantation studies, which are currently employed to evaluate
      the role of specific gene deletions in the regulation of mammary development.

PMID- 10066369
TI  - The fatty acid-binding heterocomplex FA-p34 formed by S100A8 and S100A9 is the
      major fatty acid carrier in neutrophils and translocates from the cytosol to the
      membrane upon stimulation.
AB  - Since no data are available concerning fatty acid (FA) transport in neutrophils
      we studied the presence of possible FA carriers. The kFA-p34 complex, composed of
      S100A8 and S100A9, has been implicated in the intracellular transport of
      arachidonic acid and its precursors in human keratinocytes. Here, we show that FA
      p34 is the major FA carrier in human neutrophils (nFA-p34). The complex is highly
      expressed in resting neutrophils (2.65% of cytosolic proteins) and translocates
      to the membrane fraction upon stimulation with opsonized zymosan. Comparison of
      purified nFA-p34 with kFA-p34 shows that both complexes are composed of nearly
      the same subunits and possess similar binding properties for oleic acid.
      Densitometrical analyses of 2D gels show that n and kFA-p34 contain twice as much
      S100A8 and S100A9 suggesting an estimated stoichiometry of (S100A8)2S100A9. A
      method is described allowing to distinguish n and kFA-p34 from S100A8/S100A9 homo
      and heteromer complexes that are devoid of FA-binding properties. After solvent
      extraction, we find by GC analysis linoleic acid as major endogenous ligand of
      purified kFA-p34. Our results suggest that nFA-p34, might be involved in the
      shuttling of unsaturated FA between the cytosol and the plasma membrane of
      neutrophils.

PMID- 10066370
TI  - Thrombin peptide, TP508, induces differential gene expression in fibroblasts
      through a nonproteolytic activation pathway.
AB  - Prior studies have shown that synthetic peptides representing the domain of
      thrombin responsible for high-affinity binding to fibroblasts stimulate
      chemotactic and cell proliferative signals through a nonproteolytic mechanism.
      One of these peptides, TP508, has recently been shown to be chemotactic for
      neutrophils, to enhance collagen accumulation in wounds, to enhance
      revascularization of wounds, and to accelerate the healing of incisional and open
      wounds in normal animals and in animals with impaired healing. To determine
      whether TP508 activates the proteolytically activated receptor for thrombin
      (PAR1), or the signals that are activated by PAR1, we treated human fibroblasts
      with TP508 and the PAR1-activating peptide, SFLLRNP, and analyzed the effects of
      these peptides on gene expression using differential display reverse
      transcriptase polymerase chain reaction. TP508 induces expression of a number of
      specific message fragments with short tyrosine kinase-like domains that are not
      induced by SFLLRNP. Sequencing full-length clones prepared by Marathon extension
      of TP508-induced fragments revealed that among the induced transcripts, there was
      a sequence with 88% homology to human annexin V. Northern analysis with authentic
      annexin V cDNA confirms that TP508, but not SFLLRNP, induces expression of
      annexin V in human fibroblasts. These results demonstrate that TP508 activates a
      cellular response separate from that activated through PAR1 and supports the
      hypothesis that TP508 acts through a separate nonproteolytically activated
      thrombin receptor that may be responsible for high-affinity thrombin binding and
      for nonproteolytic signals that are required for thrombin stimulation of cell
      proliferation.

PMID- 10066371
TI  - Sodium butyrate induces G2 arrest in the human breast cancer cells MDA-MB-231 and
      renders them competent for DNA rereplication.
AB  - When exposed to sodium butyrate (NaBut), exponentially growing cells accumulate
      in G1 and G2 phases of the cell cycle. In the human breast cancer cell line MDA
      MB-231, an arrest in G2 phase was observed when the cells were released from
      hydroxyurea block (G1/S interface) in the presence of NaBut. The inhibition of G2
      progression was correlated with increased contents both of total p21(Waf1) and of
      p21(Waf1) associated with cyclin A and with an inhibition of cyclin A- and B1
      associated histone H1 kinase activities measured in cell lysates, as well as with
      dephosphorylation of the RB protein. A decrease in the cell contents of cyclins A
      and B1 was also observed but this decrease was preceded by p21(Waf1)
      accumulation. When NaBut was removed from the culture medium of cells blocked in
      G2 phase, p21(Waf1) level decreased and, instead of proceeding to mitosis, these
      cells resumed a progression toward DNA rereplication. These results suggest that
      the induction of p21(Waf1) by NaBut leads to the inhibition of the sequential
      activation of cyclin A- and B1-dependent kinases in this cell line, resulting in
      the inhibition of G2 progression and rendering the cells competent for a new cell
      division cycle.

PMID- 10066372
TI  - Identification of a 220-kDa membrane tumor-associated antigen by human anti-UK114
      monoclonal antibodies selected from the immunoglobulin repertoire of a cancer
      patient.
AB  - Human monoclonal antibodies (HuMAb) specific for a 14-kDa perchloric acid-soluble
      protein (defined as UK114) were produced by somatic fusion of the human-mouse
      myeloma K6H6/B5 with Epstein-Barr virus-transformed peripheral B lymphocytes from
      a cancer patient previously treated with UK101 preparations, containing the UK114
      protein. Three IgM-secreting clones were selected on the criteria of specificity
      for the purified UK114 protein immobilized onto plastic and adapted to grow in a
      serum-free medium. The reactivity of these antibodies showed a broad distribution
      pattern restricted to fresh tumor tissues and tumor cell lines, mainly of the
      adenocarcinoma type. None of the normal cells, nonmalignant cell lines, and
      normal tissues surrounding the neoplastic lesions were reactive. The
      immunochemical analysis of the target antigens showed that the HuMAb recognize a
      molecule of 220 kDa selectively expressed by the surface of tumor cells, as well
      as a cytoplasmic 14-kDa protein. The 220-kDa antigen was different from other
      tumor-associated antigens with similar molecular mass and, so far, unique. In the
      presence of human complement, two of three HuMAb are cytotoxic for tumor cells
      expressing the 220-kDa surface antigen. The tumor specificity and the lytic
      ability attributed to these HuMAb are promising features for the exploration of
      future clinical applications.

PMID- 10066373
TI  - Laminin 5 promotes activation and apoptosis of the T cells expressing alpha3beta1
      integrin.
AB  - By introducing an alpha3 gene-containing plasmid into a human T cell line Jurkat,
      we prepared the T cells, which express a high level of the alpha3beta1 integrin,
      to assess the role of laminin 5 in the skin immune system. The alpha3beta1
      expressing T cells adhered to laminin 5 and exhibited spreading. These adhered T
      cells showed a significant tyrosine phosphorylation of intracellular proteins
      including p59(fyn) upon T-cell receptor (TCR) stimulation. Six hours after cross
      linking TCR, these cells on laminin 5 secreted a three times higher level of IL-2
      than those on a BSA-coated plate. Twenty hours after the stimulation, 48% of the
      alpha3beta1-expressing T cells on laminin 5 caused apoptosis. The protein level
      of cyclin D3 and E decreased, while that of p53 increased in these T cells. These
      data suggest that laminin 5 may play at least two regulatory roles for T cell
      functions: augmentation of IL-2 production by antigen-stimulated T cells and
      induction of apoptosis in these T cells.

PMID- 10066374
TI  - Delimitation of two regions in the 90-kDa heat shock protein (Hsp90) able to
      interact with the glucocorticosteroid receptor (GR).
AB  - The role of the 90-kDa heat shock protein (Hsp90) as a chaperone and its
      regulatory functions for cellular proteins such as the glucocorticosteroid
      receptor (GR) depends on the direct interaction of the Hsp90 with the
      corresponding protein as part of a multiprotein complex. The search for the amino
      acid sequence(s) in Hsp90 involved in interaction with the human GR has been
      carried out by mutational deletion analysis in whole cells, studying the effects
      of interaction on the nucleocytoplasmic distributions of transiently expressed
      Hsp90 and GR derivatives in COS-7 cells. Using a recently developed confocal
      microscopic immunofluorescence method that allows quantification of the
      nucleocytoplasmic ratios of the proteins in individual cells and statistical
      comparison of cell populations, two subregions of the Hsp90 molecule have been
      defined that allow interaction with GR (residues 206-291 and 446-581). The latter
      region may play a fundamental role in the interaction, while the former may
      merely stabilize the binding to GR of the intact Hsp90 molecule. Moreover, the
      dissection of the Hsp90 molecule allowed us to define two regions displaying
      nuclear localization activity (residues 1-206 and 381-581), followed by two
      regions having a predominantly cytoplasmic localization activity (residues 287
      381 and 581-728) and counteracting the nuclear localization activities.

PMID- 10066375
TI  - Transforming growth factor beta-1 up-regulates clusterin synthesis in thyroid
      epithelial cells.
AB  - Porcine epithelial cells in primary culture seeded on plastic substratum form a
      monolayer containing pseudo-vesicles. When cultured in the presence of
      thyreotropin (TSH) thyrocytes adopted a follicular-like structure and formed
      clusters. Transforming growth factor beta-1 (TGFbeta1) induced a rapid spreading
      of the TSH-treated cells only. At the same time, TGFbeta1 enhanced clusterin
      protein and mRNA expression. The increase of clusterin synthesis was proportional
      to the TGFbeta1 concentration in the culture medium. Tunicamycin abolished the up
      regulation of whole clusterin synthesis and morphological changes. The activator
      protein-1 binding site partly directed the TGFbeta1-stimulated clusterin
      expression. Phorbol ester caused rapid spreading of the cells with disappearance
      of vesicular and follicular structures. It decreased clusterin mRNA and protein
      expression, but increased Mr 45, 000 protein secretion in both TSH-treated and
      nontreated cells. Up-regulation of clusterin expression may be a marker of
      TGFbeta-mediated thyrocyte dedifferentiation.

PMID- 10066376
TI  - Different types of ROS-scavenging enzymes are expressed during cutaneous wound
      repair.
AB  - Injury to the skin initiates a series of events including inflammation, new
      tissue formation, and matrix remodeling. During the early inflammatory phase,
      polymorphonuclear leukocytes and macrophages infiltrate the wounded tissue. Once
      activated, they produce large amounts of reactive oxygen species (ROS) as part of
      their defense mechanism. Although this process is beneficial, increased levels of
      ROS can inhibit cell migration and proliferation and can even cause severe tissue
      damage. Therefore, cells must develop strategies for the detoxification of these
      molecules. To gain insight into the mechanisms which underlie this process, we
      analyzed the temporal and spatial expression pattern of various ROS-scavenging
      enzymes during the healing process of full-thickness excisional wounds in mice.
      Here we demonstrate a strong mRNA expression of two types of superoxide dismutase
      (SOD), as well as of catalase, and the selenoenzymes glutathione peroxidase
      (SeGPx) and phospholipid hydroperoxide glutathione peroxidase in normal and
      wounded skin. Most importantly, mRNA levels of the SODs and of SeGPx increased
      strongly after skin injury. In situ hybridization and immunofluorescence studies
      revealed the presence of these transcripts at multiple places in the wound,
      whereby particularly high expression levels were detected in the
      hyperproliferative epithelium and the hair follicles at the wound edge. These
      data suggest an important role of ROS-scavenging enzymes in the detoxification of
      ROS during cutaneous wound repair.

PMID- 10066377
TI  - VEGF prevents apoptosis of human microvascular endothelial cells via opposing
      effects on MAPK/ERK and SAPK/JNK signaling.
AB  - Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen,
      promotes endothelial cell survival and angiogenesis. We recently showed that VEGF
      can support the growth of human dermal microvascular endothelial cells (HDMEC)
      and human umbilical vein endothelial cells in serum-free medium. Reasoning that
      VEGF might be modulating apoptotic signal transduction pathways, we examined
      mechanisms involved in the anti-apoptotic effect of VEGF on starvation- and
      ceramide-induced apoptosis in HDMEC. We observed that VEGF ameliorated the time
      dependent increase in apoptosis, as demonstrated by morphologic observations,
      TUNEL assay, and DNA fragmentation. On the other hand, basic fibroblast growth
      factor only partially prevented apoptosis in serum-starved HDMEC; platelet
      derived growth factor-BB was completely ineffective. VEGF activated the
      phosphorylation of extracellular signal regulated kinase (ERK)1 (p44 mitogen
      activated protein kinase; MAPK) and ERK2 (p42 MAPK) in a time- and concentration
      dependent manner. Both the VEGF-induced activation and its anti-apoptotic effect
      were prevented by the specific MAPK/ERK inhibitor PD98059. The presence of VEGF
      also inhibited the sustained activation of stress-activated protein kinase/c-jun
      NH2-kinase (SAPK/JNK) caused by serum starvation and ceramide treatment.
      Activation of the MAPK pathway together with inhibition of SAPK/JNK activity by
      VEGF appears to be a key event in determining whether an endothelial cell
      survives or undergoes programmed cell death.

PMID- 10066378
TI  - The temporal relationship between protein phosphatase, mitochondrial cytochrome c
      release, and caspase activation in apoptosis.
AB  - Apoptosis is mediated by members of the caspase family of proteases which can be
      activated by release of mitochondrial cytochrome c. Additional members of the
      caspase family are activated at the cell surface in response to direct stimulus
      from the external environment such as by activation of the Fas receptor. It has
      been suggested that these upstream caspases directly activate the downstream
      caspases which would obviate a role for cytochrome c in apoptosis induced by the
      Fas receptor. We demonstrate that cytochrome c is released from mitochondria of
      Jurkat cells in response to both staurosporine and an agonistic anti-Fas antibody
      and that only the latter is inhibited by the caspase inhibitor z-VAD-FMK. This
      suggests that an upstream caspase such as caspase-8 is required for the Fas
      mediated release of mitochondrial cytochrome c. The protein phosphatase inhibitor
      calyculin A prevented cytochrome c release and apoptosis induced by both agents,
      suggesting that release of cytochrome c is required in both models. Zinc, once
      thought of as an endonuclease inhibitor, has previously been shown to prevent the
      activation of caspase-3. We show that zinc prevents the activation of downstream
      caspases and apoptosis induced by both insults, yet does not prevent release of
      mitochondrial cytochrome c. The ability of calyculin A and zinc to prevent DNA
      digestion implies that the mitochondrial pathway is important for induction of
      apoptosis by both agents. These results do not support an alternative pathway in
      which caspase-8 directly activates caspase-3. These results also demonstrate that
      a critical protein phosphatase regulates the release of cytochrome c and
      apoptosis induced by both insults.

PMID- 10066379
TI  - Establishment of persistent infection with HIV-1 abrogates the caspase-3
      dependent apoptotic signaling pathway in U937 cells.
AB  - Treatment of 26L cells, a subclone obtained from U937 cells, with TNF-alpha or
      DNA-damaging agents such as teniposide (VM26) and camptothecin (CPT) induced
      morphologically and biochemically typical apoptotic changes, including the
      activation of procaspase-3. The cells persistently infected with HIV-1 (26L/HIV),
      however, showed a marked resistance to VM26 and CPT, whereas they hardly lost the
      sensitivity to TNF-alpha. TNF-alpha-induced apoptosis of 26L/HIV cells proceeded
      without the increase in caspase-3 activity, indicating that signaling for
      apoptosis in the infected cells proceeded through an alternative caspase-3
      independent pathway which could respond to TNF-alpha but not to VM26 and CPT. The
      evidence that p-toluenesulfonyl-l-lysine chloromethyl ketone (a trypsin-like
      serine protease inhibitor) blocked VM26- and CPT-induced apoptotic changes but
      not TNF-alpha-induced apoptosis also supported the existence of the alternative
      TNF-alpha-inducible pathway. The results also suggest that a TLCK-sensitive
      protease is involved upstream of the procaspase-3 activation process and that the
      protease is essential for the progress of VM26- and CPT-induced apoptosis. The
      similar effect of HIV-1-productive infection on the apoptosis induced by the DNA
      damaging agents was also confirmed by utilizing U1 cells, which are latently HIV
      1-infected U937 cells. The cells became resistant to these agents after induction
      of the viral production by pretreatment with PMA. These results suggest that
      persistent HIV-1 infection blocks an apoptotic pathway triggered by DNA damaging
      agents through the inhibition of the procaspase-3 activation process.

PMID- 10066380
TI  - Analysis of Tax-expressing cell lines generated from HTLV-I tax-transgenic mice:
      correlation between c-myc overexpression and neoplastic potential.
AB  - Human T-cell leukemia/lymphotropic virus type I (HTLV-I) infection causes a
      variety of human diseases, including adult T-cell leukemia/lymphoma. The viral
      transactivator Tax has been implicated as a key factor in the HTLV-I-induced
      transformation pathway. To investigate the components of this pathway, we derived
      fibroblast-like cell lines, designated T6 and T9, from tail biopsies of tax
      transgenic C57BL/6 mice that do not develop tumors. Phenotypic characterization
      of T6 and T9 cells and T6-derived subclones revealed that they differ in their
      abilities to form foci in vitro and tumors in vivo. The observed differences in
      the levels of Tax expression did not correlate with their degree of neoplastic
      potential. However, a control cell line derived from a nontransgenic C57BL/6
      mouse did not form foci in vitro or tumors in vivo, indicating that Tax was
      required for the transformation process. Results of Northern analyses showed that
      the T9 cells and the highly malignant derivatives of T6 cells expressed elevated
      levels of c-myc mRNA. These findings suggest that progression of the tax
      transgenic cells toward a more malignant phenotype might involve c-myc
      deregulation.

PMID- 10066381
TI  - Signaling defect in the activation of caspase-3 and PKCdelta in human TUR
      leukemia cells is associated with resistance to apoptosis.
AB  - Exposure of the two related human leukemic cell lines U937 and TUR to
      chemotherapeutic compounds resulted in opposite effects on induction and
      resistance to apoptosis. Incubation of U937 cells with 1-beta-d
      arabinofuranosylcytosine or the etoposide VP-16 was accompanied by growth arrest
      in G0/G1 of the cell cycle and an accumulation of a population in the sub-G1
      phase which exhibited characteristics typical for the apoptotic pathway. In
      contrast, human TUR leukemia cells demonstrated no significant effects after a
      similar treatment with Ara-C and VP-16. Thus, TUR cells continued to proliferate
      in the presence of these anti-cancer drugs and the number of apoptotic cells as
      evaluated by propidium iodide staining and the detection of internucleosomal DNA
      fragmentation was significantly reduced when compared to the parental U937 cells.
      Similar effects were observed upon serum-starvation demonstrating resistance to
      apoptosis in TUR cells. Whereas induction of apoptosis is regulated by a network
      of distinct factors including the activation of proteolytically active caspases,
      we investigated these pathways in both cell lines. U937 cells demonstrated
      activation of the 32-kDa caspase-3 upon drug treatment by cleavage into the 20
      kDa activated form. However, there was no 20-kDa caspase-3 fragment detectable in
      TUR cells. Simultaneously, the enzymatic activity of caspase-3 was significantly
      increased in drug-treated U937 cells as measured in vitro by enhanced
      metabolization of a fluorescence substrate and in vivo by cleavage of an
      appropriate substrate for caspase-3, namely, protein kinase Cdelta. In contrast,
      there was little if any caspase-3 activation detectable in drug-treated TUR
      cells. Taken together, these data suggest a signaling defect in the activation of
      the caspase-3 proteolytic system in TUR cells upon treatment with
      chemotherapeutic compounds which is associated with resistance to apoptosis in
      these human leukemia cells.

PMID- 10066382
TI  - A fibrin or collagen gel assay for tissue cell chemotaxis: assessment of
      fibroblast chemotaxis to GRGDSP.
AB  - Fibroblast chemotaxis is implicated in many physiological processes, including
      wound healing and morphogenesis. We present a novel assay for chemotaxis of
      fibroblasts (and other slow-moving tissue cells) in a direct-viewing chamber
      containing a physiologically relevant three-dimensional fibrin or collagen gel in
      which long-lasting, spatially continuous gradients have been sustained for at
      least 24 h, long enough for significant fibroblast migration. This combination of
      features is not available in any alternative assay of comparable setup
      simplicity. Using a putative fibroblast chemotactic factor, the fibronectin
      peptide GRGDSP, we measured human foreskin fibroblast alignment in the direction
      along the gradient, which followed a biphasic dependence on GRGDSP concentration
      with an optimal concentration of about 10 nM. Time-lapse video microscopy
      revealed that cell migration was up the soluble GRGDSP gradient, confirming
      positive chemotaxis to GRGDSP and rejecting the possibility of dominant
      haptotaxis down the soluble GRGDSP gradient, that is, up a putative gradient of
      integrin-mediated adhesion induced by the soluble GRGDSP gradient.

PMID- 10066383
TI  - Association of human SCF(SKP2) subunit p19(SKP1) with interphase centrosomes and
      mitotic spindle poles.
AB  - In Saccharomyces cerevisiae, the initiation of DNA replication and mitotic
      progression requires SKP1p function. SKP1p is an essential subunit of a newly
      identified class of E3 ubiquitin protein ligases, the SCF complexes, that
      catalyze ubiquitin-mediated proteolysis of key cell-cycle-regulatory proteins at
      distinct times in the cell cycle. SKP1p is also required for proper kinetochore
      assembly. Little is known about the corresponding human homolog, p19(SKP1),
      except that it is expressed throughout the cell cycle and that it too is a
      component of an S-phase-regulating SCF-E3 ligase complex. Here we show by
      immunofluorescence microscopy that p19(SKP1) localizes to the centrosomes.
      Centrosome association occurs throughout the mammalian cell cycle, including all
      stages of mitosis. These findings suggest that p19(SKP1) is a novel component of
      the centrosome and the mitotic spindle, which, in turn, implies a physiological
      role of this protein in the regulation of one or more aspects of the centrosome
      cycle.

PMID- 10066384
TI  - Cell signaling defects and human disease.

PMID- 10066385
TI  - Pathogenesis of polyglutamine-induced disease: A model for SCA1.
AB  - During the past 7 years several inheritable neurological disorders have been
      found to be due to the expansion of an unstable CAG trinucleotide repeat that
      leads to an increase in the length of a polyglutamine tract within a disease
      specific protein. Based on pathological evidence obtained from the brains of
      affected individuals and transgenic mice expressing a mutant human gene, it was
      proposed that the formation of nuclear aggregates of the polyglutamine protein
      plays a critical role in pathogenesis. However, recent evidence indicates that
      this may not be the case. This review focuses on our results for one of these
      disorders, spinocerebellar ataxia type 1 (SCA1), and presents a model for SCA1
      pathogenesis.

PMID- 10066386
TI  - Altered trafficking and turnover of LAMP-1 in Pompe disease-affected cells.
AB  - The lysosome-associated membrane protein (LAMP-1) is elevated in the cells and
      plasma from lysosomal storage disorder-affected individuals; however, the
      mechanism of this elevation is not well defined. In this study we have
      investigated the synthesis, glycoprocessing, trafficking, and turnover of LAMP-1
      in human skin fibroblasts from Pompe disease patients and control individuals.
      There were similar levels of LAMP-1 synthesis in both cell types, but
      glycoprocessing was retarded in Pompe (T1/2 = 25 min) compared to control (T1/2 =
      17 min) fibroblasts. There was also a marked delay in trafficking of LAMP-1 to
      lysosomes of Pompe (T1/2 = 200 min) compared to control (T1/2 = 100 min) cells. A
      proportion of newly synthesized LAMP-1 (5.4% in Pompe and 8.5% in controls) was
      trafficked out of the cell (T1/2 = 3.5 h in controls) and, although significantly
      smaller than the lysosomal form, still had a transmembrane domain and cytoplasmic
      tail. In contrast, a soluble lysosomal pool of LAMP-1 had no tail sequence,
      suggesting that it had been clipped from the membrane. In turnover studies, LAMP
      1 was more stable in Pompe (T1/2 = 4.9 days) compared to control (T1/2 = 1. 6
      days) cells, implying either reduced proteolysis or lysosomal function, in Pompe
      cells. These results indicate altered traffic and turnover of LAMP-1 in storage
      disorders and identify different intracellular and extracellular pools of soluble
      LAMP-1, suggesting alternative trafficking pathways.

PMID- 10066387
TI  - Insulin-inducible changes in the relative ratio of PTP1B splice variants.
AB  - The skeletal muscle activity of protein tyrosine phosphates 1B (PTP1B), a
      modulator of insulin and IGF-1 signaling, is reduced in obese nondiabetic
      subjects and in subjects with type 2 diabetes in comparison with leaner,
      nondiabetic controls. PTP1B mRNA, like many other signaling molecules, including
      the insulin receptor, is alternatively spliced. Since we have shown that the
      ratio of the insulin receptor splice variants is modulated by insulin in vitro
      and is related to insulin levels in vivo, we hypothesized that the relative
      ratios of the alternatively spliced PTP1B mRNA might also vary in humans in
      proportion to the degree of hyperinsulinemia. This was tested in 21 nondiabetic
      Pima Indians, a population at increased risk for obesity and type 2 diabetes. The
      relative ratio of the PTP1B splice variants was quantified using RT-PCR of total
      RNA extracted from fractionated monocytes. The ratio of the splice variants was
      positively correlated with fasting plasma insulin concentration (r = 0.757; P =
      0.0001), 2-h plasma insulin concentration following an oral glucose tolerance
      test (r = 0.614; P = 0.01, n = 16), and percentage of body fat (r = 0.746; P =
      0.0001). These data indicate that variability in the ratio of the two splice
      variants is due, in part, to in vivo levels of chronic hyperinsulinemia. This
      simple, noninvasive assay is therefore a potential biomarker for chronic
      hyperinsulinemia, similar to the HbAlc assay in use to monitor glucose management
      in diabetic patients.

PMID- 10066388
TI  - Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a
      1.4-cM region of 1q23.
AB  - Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive
      syndrome characterized by megaloblastic anemia, deafness, and diabetes mellitus.
      A genome scan previously established linkage of this disorder to 1q23 and
      haplotype analysis defined a 16-cM critical region. Molecular genetic analyses of
      four unrelated multiplex Iranian families inheriting TRMA confirmed linkage to
      the same region and identified recombinant chromosomes which permitted refinement
      of the critical region to a narrow 1.4-cM interval. The haplotypes of the
      families differed, consistent with at least two independent mutational events.
      This refinement of the TRMA locus to less than 10% of that previously published
      should markedly facilitate the identification and evaluation of positional
      candidate and novel genes which may cause this disorder.

PMID- 10066389
TI  - Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria.
AB  - Two siblings who were found to have deficiency of glutaryl-CoA dehydrogenase were
      identified by the presence of large amounts of 3-hydroxyglutaric acid in the
      urine. Patients with this disease, termed glutaric acidemia or glutaric acidemia
      Type I, usually present with large amounts of glutaric acid in the urine, and
      amounts of 3-hydroxyglutaric acid found are less. Patients were ataxic and
      dystonic. Intelligence was normal. 3-Hydroxyglutaric acid in the urine was
      quantified by organic acid analysis via gas chromatography mass spectrometry
      (GCMS) and by stable isotope-dilution (internal standard) GCMS. Glutaryl-CoA
      dehydrogenase activity in cultured fibroblasts was found to be 2% of the control
      level. The nature of the mutations was identified, and both patients were found
      to be compound heterozygotes for R227P, which changed an arginine to a proline,
      and E365K, which changed a glutamate to a lysine.

PMID- 10066390
TI  - Bacterial species identification after DNA amplification with a universal primer
      pair.
AB  - The diagnosis of bacterial infections can be difficult and time consuming. Rapid
      and reliable molecular triage of potentially infected patients, particularly the
      young and the elderly, would prevent unnecessary hospitalizations, reduce
      associated medical costs, and improve the quality of care. Polymerase chain
      reaction (PCR) amplification utilizing a universal bacterial primer pair,
      followed by hybridization with species-specific probes, would allow rapid
      identification of the presence or absence of bacterial DNA, along with an
      identification of the bacterial species present. Molecular microbiological
      analyses will require access to bacterial strain standards that can be catalogued
      and distributed to clinical laboratories. We amplified template DNA in filter
      paper spots containing boiled bacteria from 14 clinical isolates using a
      universal primer pair for the 16S ribosomal RNA (rDNA) coding sequence. Species
      specific probes were hybridized to the amplification products for bacterial
      species identification. We conclude that template DNA can be identified with
      species-specific probes after universal bacterial amplification with a single
      primer pair. We also demonstrate a rapid and efficient method for the long-term
      storage and cataloguing of bacterial DNA for use in quality control at clinical
      laboratories adopting molecular diagnostic methodologies. We speculate that PCR
      amplification combined with species-specific probe hybridization not only will
      represent an improvement over culture-based methods in terms of speed,
      sensitivity, and cost, but will also allow for the identification of unculturable
      bacteria and emerging or reemerging pathogenic organisms.

PMID- 10066391
TI  - Mechanical function and substrate oxidation in the neonatal pig heart subjected
      to pacing-induced tachycardia.
AB  - Isolated, paced, isovolumically beating, neonatal pig ( approximately 2 days)
      hearts were perfused with a crystalloid solution during four periods: (1)
      baseline, HR 150 bpm; (2) HR-response curves, HR 150-360 bpm; (3) tachycardia, HR
      300 bpm; and (4) posttachycardia, HR 150 bpm. Group I was studied with glucose
      (5. 5 mM) as the sole substrate. During baseline, left ventricular peak systolic
      pressure (PSP) averaged 123 +/- 7 mm Hg; end diastolic pressure (EDP), 4.9 +/-
      0.4 mm Hg; relaxation time constant (Tau), 29.5 +/- 3.9 ms; glucose oxidation
      (14CO2 from [14C]glucose), 1535 +/- 96 nmol/min/gdry; and myocardial oxygen
      consumption (MVO2), 17.4 +/- 0.4 micromol/min/gdry. During tachycardia, PSP was
      83 +/- 4* mm Hg; EDP, 9.8 +/- 1.7* mm Hg; Tau, 29.9 +/- 5.4 ms; glucose
      oxidation, 1921 +/- 136* nmol/min/gdry; and MVO2, 21.1 +/- 0.7* micromol/min/gdry
      (*different from baseline, P < 0.05). Posttachycardia, all parameters returned to
      near baseline values, except EDP, which remained elevated. Group II was studied
      with glucose (5.5 mM) and palmitate (0.55 mM). When compared to those of Group I,
      the mechanical responses were similar. During baseline, glucose oxidation was 149
      +/- 24 nmol/min/gdry; palmitate oxidation, 343 +/- 28 nmol/min/gdry; and MVO2,
      18.4 +/- 0.7 micromol/min/gdry. Both oxidation rates increased significantly
      during tachycardia, indicating aerobic metabolic reserve. Posttachycardia,
      glucose oxidation returned to baseline, but palmitate oxidation remained
      elevated, suggesting enhanced beta oxidation. Group III was perfused with glucose
      (5.5 mM) and pyruvate (5.5 mM), along with iodoacetate (50 microM) to inhibit
      glycolysis. PSP was maintained, but Tau (HRs >/= 270 bpm) and EDP (HRs >/= 180
      bpm) markedly increased. In conclusion, for the isovolumically beating, neonatal
      pig heart stressed with tachycardia: (1) PSP decreases, EDP increases, and Tau
      remains relatively constant; (2) substrate oxidation is enhanced; and (3)
      glycolysis, rather than glucose oxidation, appears to be important for supporting
      ventricular diastolic function.

PMID- 10066392
TI  - Identification of a new polymorphism in the 3'-untranslated region of the human
      serotonin receptor 2C (5-HT2C) gene.
AB  - We identified a polymorphism (2831T > G) in the 3'-untranslated region of 5-HT2C
      receptor gene, approximately 100 kb from a previously reported coding sequence
      polymorphism, 796G > C (C23S). Allele frequencies were 0.90 (T) and 0.10 (G) and
      cosegregation analysis of the alleles at the two loci demonstrated frequencies of
      0.82 (GT), 0.08 (CT), 0.10 (GG), and 0 (CC). The increased informativity gained
      by analysis of both polymorphisms will prove useful for future studies of this
      gene in X-linked neuropsychiatric disorders.

PMID- 10066393
TI  - Environmental contaminants and the prevalence of hemic neoplasia (leukemia) in
      the common mussel (Mytilus edulis complex) from Puget Sound, Washington, U.S.A.
AB  - The relationship between hemic neoplasia, a blood cell disorder in bivalve
      molluscs, and chemical contaminants was evaluated in the common mussel (Mytilus
      edulis complex). Hemic neoplasia (HN) is endemic to mussel populations in Puget
      Sound. The prevalence of hemic neoplasia ranged from 0 to 30% in mussels from
      nine sites in Puget Sound, Washington. Organic chemical contamination in sediment
      from these sites range from 0.1 to 64.0 ppm of polycyclic aromatic hydrocarbons
      (PAHs) and 0.07 to 0.50 ppm chlorinated hydrocarbons. No relationship between the
      body burden of environmental contaminants and the prevalence of HN in mussels was
      identified. To evaluate the short-term ability of chemical contaminants to induce
      HN in mussels, mussels, from a site where mussels were previously determined to
      be HN free, were fed microencapsulated PAHs (composed of a mixture of
      phenanthrene, flouranthene, and benzo[a]pyrene) or PCBs (Aroclor 1254) and the
      prevalence of HN was assessed after 30 days of exposure. Although an apparent
      increase in HN prevalence (20 to 30%) was observed in all treatments groups
      except the untreated controls, no significant difference in the prevalence of HN
      was observed between the control group of mussels fed corn oil (vehicle) and
      mussels fed either PAHs or PCBs in corn oil. A long-term (180-day) exposure study
      was conducted to evaluate the influence of PAHs or PCBs in modulating the
      prevalence of HN in a mussel population already exhibiting a moderate HN
      prevalence. Mussels, from a site where mussels were previously determined to
      exhibit a background prevalence of HN, fed microencapsulated PAHs, PCBs, and corn
      oil (vehicle) over a long time period (180 days), revealed an apparent increased
      prevalence of HN (30 to 40%) above the low levels (20%) initially present.
      However, no significant difference in the prevalence of HN was observed between
      the control group of mussels fed corn oil (vehicle) and mussels fed either PAHs
      or PCBs in corn oil. Although chemical contaminants have been proposed as a
      modulating factor in the development and promotion of HN in bivalve molluscs from
      environmentally stressed and degraded habitats, we find no evidence that chemical
      contaminants induce or promote the development of HN in the mussel M. edulis
      complex.

PMID- 10066394
TI  - Interaction of catenaria anguillulae with romanomermis culicivorax 
AB  - The development of Catenaria anguillulae, at 27 degrees C, in live and heat
      immobilized Romanomermis culicivorax was studied at the ultrastructural level. C.
      anguillulae zoospores infected eggs, preparasites, and postparasites. The
      zoospores attached predominately to the head of preparasites but in postparasites
      attachment was primarily on the attenuated tail region. Zoospore attachment
      usually occurred within 4 h but at high zoospore densities attachment occurred
      within 30 min. Infection hyphae penetrated the cuticle and developed sporangial
      swellings within the nematode tissues and pseudocoelom. Sporangia produced exit
      tubes within 48 h. Those regions of the J3 and J4 nematodes infected by C.
      anguillulae became immobile whereas uninfected regions remained mobile. The J2
      infected nematodes usually died within 1-2 days. Tissues adjacent to C.
      anguillulae hyphae or developing sporangia appeared to be relatively unaffected
      and ultrastructurally normal. The lack of an apparent host response in the
      nematode suggested either a lack of hypersensitivity or a long evolutionary host
      parasite relationship. Copyright 1999 Academic Press.

PMID- 10066395
TI  - Successful parasitation of locusts by entomopathogenic nematodes is correlated
      with inhibition of insect phagocytes.
AB  - The entomopathogenic nematodes Heterorhabditis megidis and Steinernema feltiae
      turned out to be successful antagonists of the orthopteran insects Locusta
      migratoria and Schistocerca gregaria. The death rate of locusts maintained on
      nematode-inoculated sand was remarkably high. Even dosages as low as one nematode
      per cubic centimeter of sand killed approximately 50% of the locusts within 10
      days. The impact of parasitation on locusts' immune defense was closely
      investigated for L. migratoria parasitized by H. megidis. Adult locusts died
      within 30-35 h after being fed with 50 infective H. megidis juveniles. Within the
      first 30 h after ingestion of the nematodes, locust hemolymph was assayed for
      alterations in the humoral and cellular defense components and for the presence
      of the nematode-associated Photorhabdus luminescens bacteria. Humoral defense was
      generally low without any correlation to the state of parasitation. There was no
      detectable activity against Escherichia coli and only little lysozyme-like
      activity against Micrococcus luteus. In contrast, cellular defense components
      were strongly influenced by parasitation. Most interestingly, the phagocytic
      capacity of the hemocytes was already hampered 12 h after oral application of the
      nematodes, whereas considerable hemocyte death occurred not earlier than 24 h
      after feeding. The nematode-associated bacteria could be detected in hemolymph of
      some of the nematode-fed locusts as early as 3 h after feeding and in all
      hemolymph samples after 24 h. Supernatants from isolated P. luminescens cultures
      were able to inhibit the L. migratoria phagocytes in vitro; thus the successful
      parasitation appears to be dependent on an inhibition by bacteria-released
      compounds rather than on overloading or simply killing of the phagocytic active
      hemocytes.

PMID- 10066396
TI  - Studies on rickettsia-like organism disease of the tropical marine pearl oyster
      I: the fine structure and morphogenesis of pinctada maxima pathogen rickettsia
      like organism 
AB  - The present paper reports for the first time the discovery of a rickettsia-like
      organism (RLO) in the cultured tropical marine pearl oyster Pinctada maxima with
      mass mortality in the Hainan Province of China. This organism parasitizes the
      cytoplasm of host cells and forms intracytoplasmic eosinophilic inclusions. These
      organisms are extremely pleiomorphic in shape and average 967 x 551 nm in size,
      as measured in cross sections of transmission electron micrographs. The organisms
      exhibit clearly recognizable ultrastructural characteristics of prokaryotic
      bacteria-like cells, including two trilaminar membranes, an increasing electron
      dense periplasmic ribosome zone, and a thread-like DNA nucleoidal structure. In
      addition to the above prokaryotic characteristics, the following unique
      biological characteristics were confirmed by TEM: (i) These organisms are usually
      located in host cells in two ways, namely, free in the cell cytoplasm and
      involved within membrane-limited phagolysosomes; (ii) The organisms exist in two
      morphological cell types, namely a small cell variant (SCV) and a large cell
      variant (LCV). The most important morphological difference between two cell types
      is that the SCV is obviously ribosome-rich in the periphery of the body, which
      makes SCV more electron-dense in the cytoplasm and narrower in the central
      nucleoid area than the LCV; (iii) Two propagative modes of the organisms,
      transverse binary fission and budding, are observed in cytoplasm and
      phagolysosomes of host cells under TEM, in which the budding is more often seen
      in phagolysosomes. These characteristics indicate that the organism is a separate
      species in the family Rickettsiaceae and should be classified into the genus
      Rickettsia. On the basis of the existence of the two propagative modes and two
      cell types, and intracellular location, we propose a developmental cycle for this
      organism which includes a vegetative differentiation stage to develop LCV by
      transverse binary fisson and a budding differentiation stage to develop resistant
      SCV. Copyright 1999 Academic Press.

PMID- 10066397
TI  - Histopathological effects of tannic acid on the midgut epithelium of some aquatic
      Diptera larvae.
AB  - The impact of tannins on larval Nematocera was investigated by an extensive
      survey of the relative toxicity of tannic acid in Diptera larvae representative
      of mosquito communities from alpine hydrosystems (Culicidae, Chaoboridae,
      Chironomidae, and Simuliidae) together with a nonindigenous vector competent
      Culicidae species. Bioassays indicate that exposure to tannic acid at
      concentrations from 0.25 to 4 mM is deleterious for Culex pipiens, Simulium
      variegatum, and Chironomus annularius, but not for Aedes, Anopheles, Culiseta,
      and Chaoborus species. Histopathological observations reveal that, among the
      target organs of tannic acid, mainly the midgut epithelium is affected by
      treatment. However, the extent of degeneration varies according to the taxon, the
      duration of the treatment, and the concentrations assayed. The vulnerability of
      epithelial cells differs among cell types, clear cells of the anterior midgut
      showing symptoms of intoxication before dark cells of the posterior midgut. The
      toxic effects of tannic acid are discussed, particularly in comparison to those
      of insecticidal bacteria, in order to evaluate the potential for use of tannins
      in the regulation of larval populations of dipteran pests.

PMID- 10066398
TI  - Virus-like particles in the ovaries of microctonus aethiopoides loan
      (Hymenoptera: braconidae), a parasitoid of adult weevils (Coleoptera:
      curculionidae) 
AB  - The morphology of the female reproductive system of Microctonus aethiopoides is
      described and illustrated, and an ultrastructural examination of the ovaries was
      carried out. Virus-like particles (VLPs) were initially found in the ovarial
      epithelial cells of females from pre-adult emergence from the pupal cocoon until
      at least 5 days after emergence. The particles assembled in the nucleus of the
      epithelial cells, apparently being synthesized de novo in association with a
      putative virogenic stroma, and they moved into the lumen of the ovarioles
      surrounding the developing eggs. VLPs were also found in some other cells in both
      male and female M. aethiopoides. VLPs have not been found in M. hyperodae or the
      New Zealand native species M. zealandicus. The function of the VLP and its
      possible role in potential parasitoid host range determination are discussed.
      Copyright 1999 Academic Press.

PMID- 10066399
TI  - Natural host range and prevalence of the genus strongwellsea (Zygomycota:
      entomophthorales) in denmark 
AB  - The natural occurrence and host range of species of the insect pathogenic fungal
      genus Strongwellsea [Zygomycota: Entomophthorales] were studied by extensive
      sampling and examination of adult Diptera [Cyclorrhapha]. The host range for
      Strongwellsea spp. was significantly enlarged. Three families were documented as
      new hosts: Muscidae (three species), Calliphoridae (one species), and
      Sarcophagidae (one species). Further, within the family Anthomyiidae six new host
      species were recorded and three new host species were documented in the
      Fanniidae. Strongwellsea castrans was identified as the pathogen in the
      Anthomyiids, while records from Fanniidae belonged to S. magna. The records of S.
      magna were the first outside the type locality (California). Primary conidia
      morphology indicated that muscid and calliphorid species were infected by three
      undescribed species of Strongwellsea. For the sarcophagid fly, no conidia were
      encountered, so the Strongwellsea species could not be identified. The tested
      sampling methods had each different advantages. Sweep netting and diagnosis in
      situ gave the best opportunity to sample a high number of infected dipterans per
      time unit spend, while sweep netting followed by incubation in the laboratory was
      the only method for the documentation of resting spores. The prevalence of S.
      castrans in the cabbage root fly Delia radicum was obtained by two methods:
      Samples collected by sweep net and incubated and water trap samples. Water trap
      captures gave higher prevalences of conidial infections than sweep-net captures.
      Measured prevalences of Strongwellsea spp. infections are therefore highly
      dependent on sampling method. The occurrence of resting spores of S. castrans in
      D. radicum was almost exclusively restricted to females and varied during the
      season. In samples from 1988 through 1993, no infected females in June contained
      resting spores, while 43.0% of the S. castrans-infected females from samples in
      August contained resting spores. During September and October, a decreasing
      proportion of S. castrans-infected D. radicum contained resting spores. The
      results document that species from the genus Strongwellsea are common fungal
      pathogens of adult flies from different families, occasionally with high
      prevalences. It also appears that the two described species of Strongwellsea, S.
      castrans and S. magna, have a range of dipterous host species that may always
      belong to a single family, Anthomyiidae and Fanniidae, respectively. Our data
      shows also that the host family Muscidae may be exploited by two new species of
      Strongwellsea. Copyright 1999 Academic Press.

PMID- 10066400
TI  - Yield, biological activity, and field performance of a wild-type Helicoverpa
      nucleopolyhedrovirus produced in H. zea cell cultures.
AB  - This paper reports studies of the in vitro production of a virus from Helicoverpa
      armigera (HaSNPV) and its possible use as a specific Helicoverpa/Heliothis
      larvicide. Growth kinetics of Helicoverpa zea (H. zea) cells and virus occlusion
      body yields were compared in three SF900II-based media, namely, SF900II (serum
      free), SF900II + 1% serum, or SF900II + 10% serum. Viable cell densities were
      usually higher in the media supplemented with serum than in the serum-free
      medium; however, in the serum-free medium, cell diameters were 1.7 times greater
      (i.e., individual cell volumes were five times larger). Both volumetric
      production of virus occlusion bodies and production per cell were higher in the
      serum-free medium than in the media supplemented with serum. However, the
      infectivity of the occlusion bodies from the serum-free medium was less than that
      with those from the medium supplemented with 10% serum, when compared in
      bioassays employing newly hatched larvae. The infectivity of the in vitro
      produced occlusion bodies was also less than that of in vivo produced occlusion
      bodies in a commercially available virus product, GemStar. High levels of
      infection of H. armigera larvae obtained in a preliminary field assessment on
      preflowering tomatoes using the in vitro produced occlusion bodies indicated the
      suitability of the in vitro process for biopesticide production.

PMID- 10066401
TI  - Aggregation of entomopathogenic nematodes, heterorhabditis spp. and steinernema
      spp., among host insects at 9 and 20 degrees C and effects on efficacy 
AB  - The negative binomial distribution (NBD) with density-dependent k was used to
      test and describe the distribution of nematodes in Otiorhynchus sulcatus,
      Galleria mellonella, and Spodoptera exigua at 9 and 20 degrees C. Aggregation was
      greater in O. sulcatus than in the other two hosts. In case of G. mellonella
      exposed to the heterorhabditid HF85, the distribution of nematodes in the insects
      was random. There was only a small effect of low temperature on aggregation; this
      effect was stronger for O. sulcatus than for the other two hosts. Aggregation of
      nematodes among insects in a population increases the infection chance of already
      infected insects and decreases the infection chance of uninfected insects.
      Consequently, more nematodes will have to penetrate O. sulcatus than G.
      mellonella or S. exigua to cause the same proportion of infection in a
      population. The relevance of aggregation of nematodes for control O. sulcatus is
      discussed. Copyright 1999 Academic Press.

PMID- 10066402
TI  - Lytic activity and biochemical properties of lysozyme in the coelomic fluid of
      the sea urchin strongylocentrotus intermedius 
AB  - Lysozyme was identified in the coelomic fluid including coelomocytes of the sea
      urchin Strongylocentrotus intermedius, and its lytic activity and biochemical
      properties were examined in this study. The urchin lysozyme was
      electrophoretically fractionated to a single lytic band of about 14 kDa. No
      distinct difference in the lytic activity of this enzyme was found between
      urchins held at two temperatures, 11 degrees and 25 degrees C. The lysozyme of
      this species was purified through several procedures: salting out with ammonium
      sulfate, precipitation by ethanol saturation, gel filtration with a Biogel
      column, and an affinity chromatography with a heparin Sepharose column. The
      combination method of Biogel filtration and affinity chromatography resulted in
      the most purified lysozyme fraction, but we could not obtain a single protein
      band in SDS-PAGE. In addition, anti-hen egg white lysozyme (HEWL) antibody was
      produced and confirmed to react specifically with the urchin lysozyme in this
      study. Therefore, the HEWL antibody may be available for examining the lytic
      activity of lysozyme at an individual level to determine the biodefense activity
      of sea urchins. Copyright 1999 Academic Press.

PMID- 10066403
TI  - Sporulation of Beauveria bassiana on cadavers of Triatoma infestans after
      infection at different temperatures and doses of inoculum.

PMID- 10066404
TI  - Leucothecium emdenii: A novel larvicidal fungus against mosquito larvae.

PMID- 10066405
TI  - Chemical stimulation of productivity and pathogenicity of entomopathogenic
      nematodes 
AB  - Under laboratory conditions, the treatment of Steinernema carpocapsae and
      Heterorhabditis bacteriophora entomopathogenic nematodes with either Mg or Mn(II)
      ions produced an increase in their productivity and pathogenicity against Sitona
      lineatus weevil, pupae, and larvae. Copyright 1999 Academic Press.

PMID- 10066406
TI  - Iridescent virus infection in Culicoides variipennis sonorensis and interactions
      with the mermithid parasite Heleidomermis magnapapula.

PMID- 10066407
TI  - Insecticidal efficacy of a recombinant baculovirus expressing JHE-KK, a modified
      juvenile hormone esterase.

PMID- 10066409
TI  - Heartfelt Farewell.

PMID- 10066410
TI  - Introduction to the Focused Issue: The Microcirculation as a Foundation of
      Cardiovascular Disease.

PMID- 10066411
TI  - ISHR Members Business Meeting May 30, 1998. Minutes.

PMID- 10066412
TI  - Volume contents and index.

PMID- 10066413
TI  - Specific sandwich-type enzyme immunoassays for smooth muscle constricting novel
      31-amino acid endothelins.
AB  - We established highly sensitive and specific sandwich-enzyme immunoassays (EIAs)
      for three newly discovered bioactive 31-amino acid endothelins [ETs(1-31)], which
      can detect as little as 0.16 pg/well of ET-1(1-31), 0.39 pg/well of ET-2(1-31),
      and 0.16 pg/well of ET-3(1-31). The EIAs showed no crossreactivity with 21-amino
      acid endothelins [ETs(1-21)] or big ETs at the usual assay concentrations below 1
      5 ng/ml. In reversed-phase HPLC, immunoreactive ETs(1-31) in the granulocytes of
      normal human subjects eluted at the exact positions of authentic ETs(1-31),
      except for the presence of one additional unknown immunoreactive ET-1(1-31). The
      results also indicate that ETs(1-31) exist in the granulocytes at levels higher
      than or similar to those of ETs(1-21). This study is the first to establish EIAs
      for novel bioactive ETs(1-31). These assays can be utilized to assess the
      pathophysiological roles of ETs(1-31).

PMID- 10066414
TI  - Molecular modeling and experimental approaches toward designing a minimalist
      protein having Fc-binding activity of Staphylococcal protein A.
AB  - Protein A (PA), a cell wall constituent of Staphylococcus aureus, has got the
      unique property of binding with the Fc fragment of IgG from various species. The
      sequence data indicate five highly homologous Fc-binding regions in protein A.
      Computer sequence analysis provided the tryptic and chymotryptic fragments of IgG
      binding domains of protein A. Molecular modeling in conjunction with molecular
      mechanical calculation has been used to search for the smallest possible
      proteolytic fragments of PA, still retaining Fc-binding activity. A 20-residue
      peptide (typtic fragment) and a 16-residue peptide (chymotryptic fragment) have
      been indicated, by molecular modeling studies, to possess IgG-binding affinity
      comparable to that of the B domain of Protein A. Binding of a 20-residue peptide
      has been substantiated experimentally by immunoprecipitation, capillary
      electrophoresis, and circular dichroism spectroscopic analyses.

PMID- 10066415
TI  - Transverse elasticity of myofibrils of rabbit skeletal muscle studied by atomic
      force microscopy.
AB  - Surface structure of myofibrils of rabbit skeletal muscle and their transverse
      elasticity were studied by atomic force microscopy. Images of myofibrils had a
      periodic structure characteristic of sarcomeres of skeletal muscle fibers. The
      transverse elasticity distribution in the sarcomere was determined based on force
      distance curves measured at various loci of single myofibrils. The Z-line in
      rigor myofibrils was the most rigid in all the loci of myofibrils studied under
      various physiological conditions. The overall transverse elasticity of myofibrils
      decreased in the order in rigor solution > +AMPPNP solution > relaxing solution.
      The "apparent" transverse Young's modulus of myofibrils estimated at the overlap
      region between thin and thick filaments was 84.0 +/- 18.1, 37.5 +/- 14.0, and
      11.5 +/- 3.5 kPa in rigor, +AMPPNP, and relaxing solution respectively.

PMID- 10066416
TI  - Isolation and partial characterization of an extracellular low-molecular mass
      component with high phenoloxidase activity from Thermoascus aurantiacus.
AB  - An extracellular low-molecular mass component (LMMC) with catalytic properties
      was isolated from liquid cultures containing wheat bran of ascomycete
      thermophilic Thermoascus aurantiacus. The partially purified LMMC showed very
      high activity with typical phenoloxidase substrates in the absence of hydrogen
      peroxide at acidic pH (2.8). However, in this pH range, the phenoloxidase (PO)
      activity was quickly lost. The LMMC showed a high optimum temperature (80 degrees
      C) and an elevated thermostability. The molecular mass of the component estimated
      by gel filtration chromatography was 530 Da. IR and 1H- and 13C-NMR spectra
      indicated the presence of hydroxamic acid moiety. Qualitative determination of
      metal ions by several techniques revealed the presence of mainly iron associated
      with this structure. Iron may be the responsible for the ability for catalyze
      oxidation reactions, such as o-dianisidine oxidation, by the LMMC. These results
      suggested the existence of a hydroxamate-type metal-binding component, most
      likely hydroxamate siderophore. In addition, the chrome azurol S (CAS) universal
      assay for noncomplexed siderophores detection revealed the production of these
      compounds by T.aurantiacus in solid and liquid media.

PMID- 10066417
TI  - Genomic organization and regulation by dietary fat of the uncoupling protein 3
      and 2 genes.
AB  - Uncoupling protein-1 (UCP1) dissipates the transmitochondrial proton gradient as
      heat. UCP2 and UCP3 are two recently discovered homologues that also have
      uncoupling activity and thus presumably have a role in energy homeostasis. We now
      report the genomic structure of murine UCP3 (7 exons) and UCP2 (8 exons). UCP3 is
      approximately 8 kilobases upstream of UCP2. An UCP3 variant mRNA, UCP3S, was also
      found and characterized. The effect of a high fat diet (45% versus 10%) on UCP3
      and UCP2 mRNA levels was measured. Eating the 45% fat diet for eight weeks caused
      greater weight gain in AKR and C57BL/6J mice than in the obesity-resistant A/J
      mice. The high fat diet increased muscle UCP3 expression twofold in C57BL/6J
      animals. UCP2 expression increased slightly on the 45% fat diet in white adipose
      of AKR mice, but not in A/J or C57BL/6J mice. In skeletal muscle, UCP2 expression
      showed little variation with diet. Thus, UCP2 and UCP3 expression levels change
      in response to diet-induced obesity, but the changes are modest and depend on the
      tissue and genotype. The data suggest that it is not a reduction in UCP2 or UCP3
      expression that causes obesity in the susceptible mice.

PMID- 10066418
TI  - G protein-mediated mitogen-activated protein kinase activation by two dopamine D2
      receptors.
AB  - Two isoforms of dopamine D2 receptor, D2L (long) and D2S (short), differ by the
      insertion of 29 amino acids specific to D2L within the putative third
      intracellular loop of the receptor, which appears to be important in selectivity
      for G-protein coupling. We have generated D2L- and D2S-expressing Chinese hamster
      ovary (CHO) cells, and regulation of the mitogen-activated protein kinase (MAPK)
      pathway was examined in these cells. Both D2L and D2S mediated a rapid and
      transient activation of MAPK with dominant activation of p42-kDa MAPK. Pertussis
      toxin treatment completely abrogated stimulation of MAPK mediated by D2L and D2S,
      demonstrating that both receptors couple to pertussis toxin-sensitive G proteins
      in this signaling. Stimulation of MAPK mediated by both D2L and D2S receptor was
      markedly attenuated by coexpression of the C-terminus of beta-adrenergic receptor
      kinase (betaARKct), which selectively inhibits Gbetagamma-mediated signal
      transduction. Further analysis of D2L- and D2S-mediated MAPK activation
      demonstrated that D2L-mediated MAPK activation was not significantly affected by
      PKC depletion or partially affected by genistein. In contrast, D2S-mediated MAPK
      activation was potentially inhibited by PKC depletion and genistein was capable
      of completely inhibiting D2S-mediated MAPK activation. Together, these results
      suggest that D2L- and D2S-mediated MAPK activation is predominantly Gbetagamma
      subunit-mediated signaling and that protein kinase C and tyrosine
      phosphorylations are involved in these signaling pathways.

PMID- 10066419
TI  - Gangliosides GD1a and GM3 induce interleukin-10 production by human T cells.
AB  - Gangliosides are sialic acid-containing glycosphingolipids and exhibit various
      physiologic functions. Gangliosides GD1a and GM3 strongly induced interleukin-10
      (IL-10) protein secretion and mRNA expression in T cells from normal human
      subjects while the other gangliosides were ineffective. IL-10 induction by both
      gangliosides was completely blocked by protein tyrosine kinase (PTK) inhibitors,
      herbimycin A, genistein, and tyrphostin AG 1288, but not by other signal
      transduction inhibitors. These results suggest that GD1a and GM3 may induce IL-10
      production in T cells by regulating the PTK-dependent signaling pathway. These
      gangliosides may thus act as important immunoregulators via IL-10.

PMID- 10066420
TI  - Recruitment of TBP or TFIIB to a promoter proximal position leads to stimulation
      of RNA polymerase II transcription without activator proteins both in vivo and in
      vitro.
AB  - Eukaryotic transcriptional activators may function, at least in part, to
      facilitate the assembly of the RNA polymerase II (pol II) preinitiation complex
      at the core promoter region through their interaction with a subset of components
      of the basal transcription machinery. Previous studies have shown that artificial
      tethering of TATA-binding protein (TBP) to the promoter region is sufficient to
      stimulate pol II transcription in yeast. To test whether this phenomenon is a
      general one in eukaryotic pol II transcription, the DNA-binding domain of yeast
      GAL4 was fused to either Xenopus laevis TBP or TFIIB in order to enable these
      factors to be efficiently positioned near the transcription start site in a GAL4
      binding site-dependent manner. We found that GAL4-xTBP as well as GAL4-xTFIIB
      directed an increased level of transcription without involvement of the
      transcriptional activator, suggesting that incorporation of these basal factors
      into a preinitiation complex (PIC) is a major rate-limiting step accelerated by
      activator proteins in metazoans. These results show that transcription activation
      by artificial recruitment of basal transcription machinery can be observed in
      general among eukaryotic transcription both in vivo and in vitro. Furthermore,
      failure of recovery of transcription by adding GAL4-xTFIIB after depletion of
      endogenous TBP with TATA oligo competitor suggests that recruitment of TBP cannot
      be bypassed for Pol II transcription.

PMID- 10066421
TI  - Inactivation of mitogen-activated protein kinases by a mammalian tyrosine
      specific phosphatase, PTPBR7.
AB  - Mitogen-activated protein kinase (MAPK) is inactivated through dephosphorylation
      of tyrosyl and threonyl regulatory sites. In yeast, both dual-specificity and
      tyrosine-specific phosphatases are involved in dephosphorylation. In mammals,
      however, no tyrosine-specific phosphatase has been identified molecularly to
      dephosphorylate MAPK in vivo. Recently, we and others have cloned a murine
      tyrosine-specific phosphatase, PTPBR7/PTP-SL, which is expressed predominantly in
      the brain. Here we report inactivation of the extracellular signal-regulated
      kinase (ERK) family MAPK by PTPBR7. PTPBR7 made complexes with ERK1/ERK2 in vivo
      and dephosphorylated ERK1 in vitro. When overexpressed in mammalian cells, wild
      type PTPBR7 suppressed the phosphorylation and activation of ERK by epidermal
      growth factor (EGF), nerve growth factor (NGF), and constitutively active MEK1, a
      mutant MAPK kinase. In contrast, catalytically inactive and ERK-binding-deficient
      mutants revealed little inhibition on the ERK cascade. These results indicate
      that PTPBR7 suppresses MAPK directly in vivo.

PMID- 10066422
TI  - Uptake of liposomes containing phosphatidylserine by liver cells in vivo and by
      sinusoidal liver cells in primary culture: in vivo-in vitro differences.
AB  - The interaction with liver cells of liposomes containing different mol fractions
      of phosphatidylserine was investigated in vivo and in vitro. Increasing the
      amount of liposomal phosphatidylserine from 10 to 30 mol% leads to a faster blood
      disappearance of the liposomes. Within the liver, which is mainly responsible for
      this elimination, these liposomes are only taken up by the hepatocytes and
      Kupffer cells. By contrast, sinusoidal endothelial cells, in vitro, do bind and
      internalize liposomes containing >/=30% phosphatidylserine at least as actively
      as Kupffer cells. The uptake by endothelial and Kupffer cells is inhibited by
      poly(inosinic acid) and other anionic macromolecules, suggesting the involvement
      of scavenger receptors. The lack of liposome uptake by endothelial cells under in
      vivo conditions can be attributed to plasma effects since addition of various
      sera caused severe reduction of in vitro uptake of liposomes. In vivo the
      phosphatidylserine head groups may be masked by plasma proteins adsorbed to the
      liposomal surface, thus preventing recognition by receptors, which are
      intrinsically able to recognize phosphatidylserine.

PMID- 10066423
TI  - Cloned prokaryotic iron superoxide dismutase protects yeast cells against
      oxidative stress depending on mitochondrial location.
AB  - Superoxide dismutase (SOD) is considered to be the first line of defense against
      oxygen toxicity. It exists as a family of three metalloproteins with copper,zinc
      (Cu,ZnSOD), manganese (MnSOD), and iron (FeSOD) forms. In this work, we have
      targeted Escherichia coli FeSOD to the mitochondrial intermembrane space (IMS) of
      yeast cells deficient in mitochondrial MnSOD. Our results show that FeSOD in the
      IMS increases the growth rate of the cells growing in minimal medium in air but
      does not protect the MnSOD-deficient yeast cells when exposed to induced
      oxidative stress. Cloned FeSOD must be targeted to the mitochondrial matrix to
      protect the cells from both physiological and induced oxidative stress. This
      confirms that the superoxide radical is mainly generated on the matrix side of
      the inner mitochondrial membrane of yeast cells, without excluding its potential
      appearance in the mitochondrial IMS where its elimination by SOD is beneficial to
      the cells.

PMID- 10066424
TI  - UV-Laser induced protein/DNA crosslinking reveals sequence variations of DNA
      elements bound by c-Jun in vivo.
AB  - Many proteins involved in the modulation of gene expression exert their function
      through direct interaction with DNA. The sequence specificity of these
      interactions provides the basis for many regulatory mechanisms. The sites that
      are utilized by a transcription factor are usually analyzed using in vitro
      binding studies. To detect true in vivo binding sites we developed a method,
      presented here, that allows construction of recognition element DNA (reDNA)
      libraries which represent in vivo binding sites plus flanking sequences. reDNA
      libraries can be constructed for any well-characterized transcription factor.
      Here we used this method for an in vivo study of genomic DNA elements that
      interact with the transcription factor c-Jun in rat cerebellum.

PMID- 10066425
TI  - Genomic cloning and promoter analysis of the mouse 105-kDa heat shock protein
      (HSP105) gene.
AB  - The 105-kDa heat shock protein (HSP105) is a member of the high-molecular-mass
      heat shock protein family. We have isolated and characterized the mouse HSP105
      gene including about 1.2 kb of the 5'-flanking region. The mouse HSP105 gene
      spans about 22 kb, consisting of 18 exons separated by 17 introns. Southern
      blotting analysis revealed the existence of a single copy of HSP105. Primer
      extension analysis revealed that the transcription initiation site was located
      165 bp upstream of the ATG translation initiation codon. The 5'-promoter region
      of the HSP105 gene contained a TATA box, a CAAT box, an inverted CAAT box, and
      two GC boxes. Two heat shock element (HSE) sequences were found as four nGAAn
      repeats at nt -64 and nt -128. Promoter analysis using deletion derivatives
      revealed that a minimal region which contained the two consensus HSE sequences
      was active in response to heat shock and also for constitutive expression of the
      gene.

PMID- 10066426
TI  - Quinone analogue irrecoverably paralyses the filarial parasites in vitro.
AB  - 2,3-Dimethoxy-5-methyl-1,4-benzoquinone (Q0), an analogue of ubiquinone,
      irreversibly paralyses the adult and microfilariae of the cattle filarial
      parasite Setaria digitata. The same concentration of Q0 that paralyses the
      microfilariae of S. digitata also paralyses the microfilariae of the human
      filarial parasite Wuchereria bancrofti within the same duration. Thus the
      experiments done in the model S. digitata system can well be extended to the
      human filarial system. A drug at the level of the quinone-centered energy
      generating system, perhaps an analogue of quinone like Q0, can inactivate the
      filarial parasites and may prove to be an effective drug to control filariasis.

PMID- 10066427
TI  - Photosensitization of wild and mutant strains of Escherichia coli by meso-tetra
      (N-methyl-4-pyridyl)porphine.
AB  - Wild type Escherichia coli cells as well as some mutant strains lacking specific
      DNA repair systems are efficiently killed upon visible light-irradiation after 5
      min-incubation with meso-tetra(4N-methyl-pyridyl)porphine (T4MPyP). The presence
      of oxygen is necessary for cell photoinactivation. The porphyrin appears to exert
      its phototoxic activity largely by impairing some enzymic and transport functions
      at the level of both the outer and cytoplasmic membrane. Thus, SDS-PAGE
      electrophoresis shows a gradual attenuation of some transport protein bands as
      the irradiation proceeds, while a complete loss of lactate and NADH dehydrogenase
      activities is caused by 15 min-exposure to light. On the other hand, DNA does not
      represent a critical target of T4MPyP photosensitization as suggested by the
      closely similar photosensitivity of the wild E. coli and E. coli strains
      defective for two different DNA repair mechanisms, as well as by the lack of any
      detectable alteration of the pUC19 plasmids extracted from photosensitized E.
      coli TG1 cells.

PMID- 10066428
TI  - Increase in three alpha,beta-dicarbonyl compound levels in human uremic plasma:
      specific in vivo determination of intermediates in advanced Maillard reaction.
AB  - Methylglyoxal (MGO), glypxal (GO) and 3-deoxyglucosone (3-DG) are reactive
      alpha,beta-dicarbonyl intermediates in advanced Maillard reaction, which form
      advanced glycation and oxidation end products (AGEs) by reaction with both lysine
      and arginine residues in protein. We measured these three dicarbonyl compound
      levels in human plasma to estimate the relationship between accumulation of
      alpha, beta-dicarbonyl compounds and AGE formation reactions in uremia and
      diabetes in human plasma by a highly selective and specific assay, electrospray
      ionization liquid chromatography mass spectrometry (ESI/LC/MS). We show that 3-DG
      and MGO levels are significantly higher in uremia and diabetes compared with age
      matched healthy controls. Only the GO level in uremic plasma is significantly
      higher compared to diabetes and healthy controls. In both diabetic and uremic
      patients, these dicarbonyl compounds promote AGE accumulation in vivo, and
      especially in uremic patients, increased accumulation of GO could result from
      accelerating oxidative stress.

PMID- 10066429
TI  - Benzoyl ATP is an antagonist of rat and human P2Y1 receptors and of platelet
      aggregation.
AB  - The effects of 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) on intracellular Ca2+
      mobilization and cyclic AMP accumulation were investigated using rat brain
      capillary endothelial cells which express an endogenous P2Y1 receptor, human
      platelets which are known to express a P2Y1 receptor, and Jurkat cells stably
      transfected with the human P2Y1 receptor. In endothelial cells, BzATP was a
      competitive inhibitor of 2-methylthio ADP (2-MeSADP) and ADP induced [Ca2+]i
      responses (Ki = 4.7 microM) and reversed the inhibition by ADP of adenylyl
      cyclase (Ki = 13 microM). In human platelets, BzATP inhibited ADP-induced
      aggregation (Ki = 5 microM), mobilization of intracellular Ca2+ stores (Ki = 6.3
      microM), and inhibition of adenylyl cyclase. In P2Y1-Jurkat cells, BzATP
      inhibited ADP and 2-MeSADP-induced [Ca2+]i responses (Ki = 2.5 microM). It was
      concluded that BzATP is an antagonist of rat and human P2Y1 receptors and of
      platelet aggregation. In contrast to other P2Y1 receptor antagonists (A2P5P and
      A3P5P) which inhibit only ADP-induced Ca2+ mobilization, BzATP inhibits both the
      Ca2+- and the cAMP-dependent intracellular signaling pathways of ADP. These
      results provide further evidence that P2Y1 receptors contribute to platelet ADP
      responses.

PMID- 10066430
TI  - The role of protein kinase C in laminin-mediated neurite outgrowth.
AB  - Laminin is a potent stimulator of neurite outgrowth in rat pheochromocytoma
      (PC12) cells. Here, we investigated the role of protein kinase C (PKC) in the
      mechanism of laminin-mediated neurite outgrowth in PC12 cells. Phorbol ester
      activators of PKC have been shown to have divergent effects on laminin-mediated
      neurite outgrowth. Therefore, we tested the effect of the non-phorbol PKC
      activator, indolactam V. At 1.0 microM indolactam V inhibited laminin-mediated
      neurite outgrowth by 85%. Further, the PKC inhibitor H7 blocked the inhibitory
      effect of indolactam V on laminin-mediated neurite outgrowth. Direct measurement
      of protein kinase C activity in the soluble (cytosolic) and particulate
      (membrane) fractions of PC12 cells showed that laminin failed to alter protein
      kinase C activity. These data demonstrate that PKC activation inhibits laminin
      mediated neurite outgrowth and that laminin does not activate PKC in PC12 cells.

PMID- 10066431
TI  - The identification and characterization of two promoters and the complete genomic
      sequence for the Wiskott-Aldrich syndrome gene.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by
      immunodeficiency, eczema and thrombocytopenia. The gene responsible for WAS was
      identified through positional cloning, and the function of the encoded protein
      (WASP) is still the subject of much speculation. WASP is currently thought to be
      involved in the regulation of actin polymerization in hematopoietic cells. To
      study the elements that regulate the WASP gene, we have identified the sites for
      transcription initiation. We found that two promoters were responsible for
      controlling WASP expression. Multiple transcription initiation sites were found
      immediately adjacent to the translation start site, however an alternate exon
      with a second promoter region was identified 6 kb upstream. Examination of the 5'
      sequence adjacent to the initiation sites in both promoters failed to reveal a
      TATA or CCAAT box, but numerous putative transcription factor binding sites
      including Sp1, Ets, c-Myb and PU.1 were apparent. Reporter constructs generated
      from each promoter showed functional activity in the Jurkat T-cell and HEL
      erythro-megakaryocytic cell lines. Although the alternate exon sequence was
      extremely GC rich and contained several potential binding elements, the primary
      promoter was stronger than the upstream promoter in the cell lines assayed. The
      transcription factor binding site profiles within each promoter suggested that
      they may play different roles in regulating WASP expression depending on the
      stage of differentiation and development, and the cell lineage. In this study we
      have also reported the complete nucleotide sequence of the coding and intervening
      sequences for the WASP gene. A comprehensive knowledge of the genomic structure
      and the further characterization of WASP gene expression will facilitate the
      continued investigation of mutations in WAS patients, and the eventual prospect
      of gene therapy.

PMID- 10066432
TI  - Shedding of CD163, a novel regulatory mechanism for a member of the scavenger
      receptor cysteine-rich family.
AB  - The glucocorticoid-inducible transmembrane protein CD163 is a member of the
      scavenger receptor cysteine-rich (SRCR) family which is expressed exclusively on
      human monocytes and macrophages. The expression of the protein is significantly
      downregulated in response to phorbol 12-myristate 13-acetate (PMA) by a yet
      unknown mechanism. We now demonstrate that PMA induces shedding of a soluble form
      of CD163 rather than internalization, revealing a novel regulatory mechanism for
      a member of the SRCR family. Bisindolylmaleimide I was shown to inhibit phorbol
      ester-induced shedding, thus implying an involvement of protein kinase C (PKC).
      Furthermore, cleavage could be prevented by protease inhibitors. Therefore, we
      suggest that PMA-induced activation of PKC leads to protease-mediated shedding of
      CD163. These results indicate a specific release mechanism of soluble CD163 by
      human monocytes which could play an important role in modulating inflammatory
      processes.

PMID- 10066433
TI  - Signal transduction pathways mediated by glycoprotein Ia/IIa in human platelets:
      comparison with those of glycoprotein VI.
AB  - Human platelets were activated either by glycoprotein (GP) Ia/IIa agonist
      (rhodocytin) or by a GPVI agonist (collagen-related peptide, CRP), and the
      intracellular signal transduction pathways were compared in the presence of
      various inhibitors. Rhodocytin isolated from Calloselasma rhodostoma venom was
      verified as a GPIa/IIa agonist, based on the inhibitory effects of three mAbs
      directed against GPIa. Platelet activation mediated by GPIa/IIa led to overt
      platelet aggregation, elevation of intracellular Ca2+, and tyrosine
      phosphorylation of several proteins, similar to that of GPVI. p72(syk) and
      phospholipase Cgamma2 (PLCgamma2) tyrosine phosphorylation were also observed
      with GPIa/IIa-mediated platelet aggregation, although they peaked slightly later
      than that of GPVI. In contrast to GPVI-mediated platelet activation, most of
      these phenomena induced by GPIa/IIa activation were markedly suppressed by
      acetylsalicylic acid (ASA) or cytochalasin D. These findings suggest that the
      requirements for thromboxane A2 (TXA2) production and actin polymerization, which
      are the characteristics of collagen-induced platelet activation, are derived from
      the GPIa/IIa-mediated signal transduction, but not from that of GPVI.

PMID- 10066434
TI  - In vivo and in vitro recruitment of an IkappaBalpha-ubiquitin ligase to
      IkappaBalpha phosphorylated by IKK, leading to ubiquitination.
AB  - Activation of the transcriptional factor NF-kappaB is triggered by signal
      dependent degradation of its inhibitor protein IkappaB through the ubiquitin (Ub)
      proteasome pathway. We found here that a phosphorylated IkappaBalpha
      immunoprecipitated (IP-pIkappaBalpha) from the crude extract of HeLa cells which
      had been treated with tumor necrosis factor-alpha (TNFalpha) caused a dramatic
      ubiquitination of itself, termed autoubiquitination, when incubated with ATP, Ub,
      and E1-activating and E2-conjugating enzymes. IP-pIkappaBalpha also catalyzed
      ubiquitination of an in vitro synthesized 35S-IkappaBalpha previously
      phosphorylated by IkappaB-kinase (IKK) which is referred to as
      transubiquitination. No appreciable activity of auto- and transubiquitination was
      observed in an unphosphorylated IP-IkappaBalpha. Moreover, the putative
      IkappaBalpha-Ub ligase (IkappaBalpha-E3) present in HeLa cell cytosol associated
      in vitro with an IKK-phosphorylated recombinant IkappaBalpha, a process
      independent of NF-kappaB binding to IkappaBalpha or TNFalpha stimulation.
      Replacement of the two Ser residues at positions 32 and 36 corresponding to IKK
      phosphorylation sites by Ala resulted in almost complete prevention of binding of
      an IkappaBalpha-E3 to IkappaBalpha. These results indicate that phosphorylation
      of IkappaBalpha is necessary and sufficient for recruitment of this IkappaBalpha
      E3 to associate with IkappaBalpha.

PMID- 10066435
TI  - IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1,
      cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.
AB  - Destruction of the transcriptional inhibitor IkappaB by the ubiquitin (Ub) system
      is required for signal-dependent activation of the multifunctional
      transcriptional factor NF-kappaB, but details of this ubiquitination are largely
      unknown. We report here that the IkappaBalpha-ubiquitin ligase (IkappaBalpha-E3)
      is an SCF-like complex containing Skp1, cullin-1, and two homologous F-box/WD40
      repeat proteins, betaTrCP1 and betaTrCP2. Intriguingly, all these components are
      cooperatively recruited to bind to a phosphorylated IkappaBalpha (pIkappaBalpha)
      produced by tumor necrosis factor-alpha (TNF-alpha) stimulation. IkappaBalpha-E3
      bound to pIkappaBalpha catalyzed in vitro ubiquitination of pIkappaBalpha in the
      presence of ATP, Ub, and E1-activating and E2-conjugating enzymes. Forced
      expression of betaTrCP1 and betaTrCP2 resulted in dramatic augmentation of the in
      vitro polyubiquitination activity of IkappaBalpha-E3. These results indicate that
      the long-sought IkappaBalpha-E3 is an SCF-like complex consisting of multiple
      proteins which are coordinately assembled during phosphorylation of IkappaBalpha
      in response to external signals.

PMID- 10066436
TI  - Xenobiotic-responsive element for the transcriptional activation of the rat Cu/Zn
      superoxide dismutase gene.
AB  - Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide
      radicals produced from biological oxidation and environmental stresses. A number
      of xenobiotics are toxic because they generate free radicals, such as superoxide
      and hydroxyl radicals, through a redox cycle. The xenobiotic responsive element
      (XRE) was located between the nt -268 and -262 region of the 5'-flanking sequence
      of the SOD1 gene. Functional analyses of this element by deletion, mutations, and
      heterologous promoter systems confirmed that the expression of the SOD1 gene was
      induced by a xenobiotic through the XRE. Gel mobility shift assays showed the
      xenobiotic inducible binding of the receptor-ligand complex to XRE. The
      cytoplasmic fraction from nontreated HepG2 cells also contains the factor as a
      cryptic form and prominently reveals its DNA-binding activity by incubation with
      betaNF in vitro. These results suggest that the XRE participates in the induction
      of the rat SOD1 gene by xenobiotics.

PMID- 10066437
TI  - Increase in uncoupling protein-2 mRNA expression by BRL49653 and bromopalmitate
      in human adipocytes.
AB  - Uncoupling protein-2 (UCP2) is a novel mitochondrial protein that may be involved
      in the control of energy expenditure. We have previously reported an upregulation
      of adipose tissue UCP2 mRNA expression during fasting in humans. Analysis of
      changes in metabolic parameters suggested that fatty acids may be associated with
      the increased UCP2 mRNA level. Culture of human adipose tissue explants was used
      to study in vitro regulation of adipocyte UCP2 gene expression. A 48-h treatment
      with BRL49653 and bromopalmitate, two potent activators of PPARgamma, resulted in
      a dose-dependent increase in UCP2 mRNA levels. The induction by BRL49653 was
      rapid (from 6 h) and maintained up to 5 days. TNFalpha provoked a 2-fold decrease
      in UCP2 mRNA levels. Human recombinant leptin did not affect UCP2 mRNA
      expression. The data support the hypothesis that fatty acids are involved in the
      control of adipocyte UCP2 mRNA expression in humans.

PMID- 10066438
TI  - S. aureus superantigen protein A expands CD4(+)/CD8(+)/CD19(+)/CD34(+) cells in
      mice: a potential immunorestorer.
AB  - Protein A (PA) of Staphylococcus aureus is known for its immunostimulatory, anti
      cancer, and anti-toxic properties. The present study revealed that PA stimulates
      specific immunocytes to act as a potential immunorestorer. It has also been shown
      that the percentage of various cell types bearing different clusters of
      differentiation markers, e.g., CD4(+), CD8(+), CD19(+), increases considerably
      after inoculation with PA. It has also been observed that CD34(+) progenitor
      cells of bone marrow also increased significantly (P < 0.05) upon PA treatment.
      PA significantly elevated Th-1 cytokines, e.g., IFN-gamma, TNF-alpha, and IL
      1alpha. The increased percentages of CD4(+), CD8(+), CD19(+), CD34(+) cells and
      elevated cytokine levels in PA treated animals may contribute to the reported
      anti-tumor, anti-fungal, anti-parasitic, and anti-toxic properties of PA. Since
      in various diseased conditions and during toxic drug therapy lymphocytes bearing
      such differentiation markers get suppressed, this type of approach could help in
      immunorestoration of the host. These findings might help in designing therapeutic
      approaches toward various diseases which cause immunosuppression.

PMID- 10066439
TI  - Lipophilins: human peptides homologous to rat prostatein.
AB  - Lipophilin components A, B and C are human homologues of prostatein, the major
      secreted protein of rat prostate. This report describes their cDNA sequences,
      tissue expression and chromosomal localization. Lipophilin gene products were
      widely expressed in normal tissues, especially in endocrine-responsive organs.
      The gene for lipophilin C (also called mammaglobin b) is located on chromosome
      11q12-q13.1, near the mammaglobin gene, a homologue overexpressed in many breast
      cancers. The lipophilin B gene resides on chromosome 10q23, a region deleted in
      many tumors, and the lipophilin A gene is on chromosome 15q12-q13.

PMID- 10066440
TI  - The solution structure of heregulin-alpha and a N-terminal mutant with suppressed
      activity.
AB  - NMR spectroscopy is used to compare the structure of the EGF-like domain of
      heregulin-alpha and HT1, a mutated form of heregulin-alpha with significantly
      reduced activity. HT1 is a chimeric protein that has the first seven residues of
      transforming growth factor-alpha and the sequence of heregulin-alpha from the
      first cysteine through the next 58 residues. The results demonstrate that both
      proteins share the same fold, including the triple stranded beta-sheet formed by
      the N-terminus and the B-loop. Analysis of the chemical shifts indicates that
      there are perturbations to the side chain packing of the beta-sheet. The observed
      changes in the chemical shifts show an interesting correspondence to the results
      from the homologue scan presented in the previous paper. These results indicate
      that the binding epitope for the native receptor extends across the beta-sheet
      and includes residues Leu179, Lys181, Leu209, and Lys211.

PMID- 10066441
TI  - Spatiotemporal, allelic, and enforced expression of Ximpact, the Xenopus homolog
      of mouse imprinted gene impact.
AB  - Mouse Impact is an imprinted gene encoding an evolutionarily conserved protein of
      unknown function. We isolated cDNA for the Xenopus homolog of Impact (Ximpact),
      since the clawed frog not only provides an excellent model for the study of gene
      function in early development but also allows the generation of interspecific F1
      hybrids required for the examination of allelic expression status. The predicted
      product of Ximpact shows an extreme sequence similarity to those of mouse Impact
      and its homologs in nematoda, fission yeast, and budding yeast. The transcript of
      Ximpact is present in oocytes as well as in early embryos, and its spatial
      distribution is ubiquitous in both embryonic and adult stages. An RT-PCR-RFLP
      assay using the reciprocal interspecific F1 hybrids and a DNA polymorphism
      between X. laevis and X. borealis showed that Ximpact is expressed biallelically
      when analyzed as a whole embryo. Overexpression of Ximpact by RNA microinjection
      resulted in a higher than normal rate of gastrulation defects, suggesting the
      need for tight control of its dosage in early development.

PMID- 10066442
TI  - Purification and characterization of a lymph node sulfotransferase responsible
      for 6-O-sulfation of the galactose residues in 2'-fucosyllactose and other sialyl
      LewisX-related sugars.
AB  - A microsomal galactose-6-O-sulfotransferase (Gal-6-O-Stase) from porcine lymph
      nodes, able to transfer the sulfate group from adenosine 3'-phosphate 5'
      phosphosulphate (PAPS) onto 2'-fucosyllactose (2'-FL) and other sialyl LewisX
      (sLex)-related sugars, has been purified and characterized. The enzyme was
      purified to about 35,000-fold by a combination of conventional and affinity
      chromatographic steps. The purified enzyme preparation exhibited two protein
      bands at around 80-90 and 170 kDa on 7.5% SDS-PAGE under reducing conditions.
      Both of these protein bands always comigrated in the gel when peak fractions
      containing Gal-6-O-Stase activity from the 3',5'-ADP-agarose column were
      subjected to 6% SDS-PAGE under reducing conditions. These protein bands also
      showed similar binding patterns to WGA (wheat germ agglutinin), Con A
      (concanvalin A), and EBA (elderberry agglutinin). Similarly, when the enzyme
      preparation after the hydroxylapatite step was photolabeled with 8-azido-[32P]
      PAPS, both 80-90 and 170 kDa protein bands were labeled in a specific manner.
      These results suggest a possible association of these two protein bands with the
      enzyme activity. The carbohydrate substrate specificity of this enzyme suggests
      that it is well suited to catalyze the sulphonation at the C-6 position of the
      galactose residues of oligosaccharides that are structurally similar to sLex.
      Furthermore, a survey of several porcine organs revealed that this enzyme was
      selectively expressed in lymphoid tissues such as lymph nodes (peripheral and
      mesenteric) and spleen. These findings suggest that this enzyme may be involved
      in the assembly of 3'-sialyl-6'-sulfo Lewisx, the major capping group of HEV
      ligands for L-selectin.

PMID- 10066443
TI  - Tctex2-related outer arm dynein light chain is phosphorylated at activation of
      sperm motility.
AB  - When the motility of sperm is activated, only one light chain of flagellar outer
      arm dynein is phosphorylated in many organisms. We show here that the light chain
      to be phosphorylated was shown to be light chain 2 (LC2) in rainbow trout and
      chum salmon sperm and LC1 in sea urchin sperm. Molecular analyses of the
      phosphorylated light chains from sperm flagella of the salmonid fishes and sea
      urchin revealed that the light chains are homologs of the mouse t complex-encoded
      protein Tctex2, which is one of the putative t complex distorters. These results
      suggest that mouse Tctex2 might also be a light chain of flagellar outer arm
      dynein and that the abortive phosphorylation of Tctex2/outer arm dynein light
      chain might be related to the less progressive movement of sperm.

PMID- 10066444
TI  - A long-term culture of human hepatocytes which show a high growth potential and
      express their differentiated phenotypes.
AB  - The present study succeeded for the first time in cultivating for more than 2
      months human normal hepatocytes which showed a high growth potential and
      expressed their differentiated phenotypes. Constituents of culture medium were
      critical for this culture, and the medium optimized for their growth contained
      fresh human serum, fetal bovine serum, Swiss 3T3-cell conditioned medium, L
      ascorbic acid 2-phosphate, epidermal growth factor, nicotinamide, and dimethyl
      sulfoxide. Hepatocytes steadily replicated and formed colonies which continued to
      increase in size up to around 35 days. The number of hepatocytes in the most
      replicative colonies increased 17-fold during 31 days. Cells in colonies
      expressed normal differentiated hepatocytic phenotypes for as long as 35 days.
      These hepatocytes retained normal liver functions at least for 70 days such as to
      secrete albumin, and to metabolize lidocaine and D-galactose.

PMID- 10066445
TI  - VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide
      synthase, and caveolin-1 in vascular endothelial cells.
AB  - VEGF increases endothelial cell permeability and growth by a process requiring
      NOS activity. Because eNOS activity is regulated by its interaction with the
      caveolar structural protein caveolin-1, we analyzed VEGF effects on structural
      interactions between eNOS, caveolin-1 and the VEGF receptor Flk-1/KDR. Confocal
      immunolocalization analysis of the subcellular distribution of Flk-1/KDR,
      caveolin-1 and eNOS showed that VEGF stimulated the translocation of all three
      proteins into the nucleus. This result was confirmed by cell fractionation and
      immunoblotting studies showing that levels of all three proteins within the
      caveolar compartment declined progressively after 30 and 60 min of VEGF
      treatment. The pattern was reversed for nuclear fractions. Protein levels were
      lowest in the control cultures, but increased progressively after 30 and 60 min
      of treatment. Nuclear translocation of eNOS and Flk-1/KDR within caveolae may
      represent a mechanism for targeting NO production to the nuclear compartment
      where it could influence transcription factor activation.

PMID- 10066446
TI  - Cholestanol induces apoptosis of cerebellar neuronal cells.
AB  - Cerebrotendinous xanthomatosis (CTX) is a hereditary lipid storage disease
      characterized by hyper-cholestanolemia, cerebellar ataxia, xanthoma, and
      cataract. We hypothesized that cholestanol in serum of CTX patients might induce
      neuronal cell death in the cerebellum and eventually lead to cerebellar ataxia.
      To gain support for this hypothesis we developed hyper-cholestanolemia rats by
      feeding cholestanol. Neuronal cells, especially Purkinje cells in the cerebellum
      were stained by Sudan black B only in the cholestanol-fed rats, indicating the
      deposit of cholestanol in cerebellum. To examine effects of cholestanol in vitro,
      cerebellar neuronal cells were cultured with cholestanol. The cholestanol
      concentration increased and the viability decreased in cells cultured with
      cholestanol. Apoptosis was evident in cells cultured with cholestanol more
      frequently than in control cells, determined using the terminal deoxynucleotidyl
      transferase (TdT) dUTP nick end-labeling (TUNEL) method. As activities of
      interleukin-1beta-converting enzyme (ICE) and CPP32 protease were increased in
      cells cultured with cholestanol, all these data taken together suggest that
      cholestanol induced apoptosis of cerebellar neuronal cells. Our observations may
      explain the mechanism of cerebellar ataxia of CTX patients.

PMID- 10066447
TI  - Stimulation of PC cell-derived growth factor (epithelin/granulin precursor)
      expression by estradiol in human breast cancer cells.
AB  - PC cell-derived growth factor (PCDGF) is an 88 kDa glycosylated protein isolated
      from a highly tumorigenic mouse teratoma derived cell line which is similar to
      the epithelin/granulin precursor. Using Northern blot and western blot analyses,
      we detect the expression of PCDGF mRNA and protein in MCF-7 human breast cancer
      cells. We show that 17-beta-estradiol stimulates PCDGF mRNA and protein
      expression in a time and dose-dependent manner. The stimulation of PCDGF
      expression by 17-beta-estradiol was observed as early as 4 hours and reached a
      maximum at 12 hours. Maximal stimulation of PCDGF mRNA and protein expression by
      17-beta-estradiol was observed at a concentration of 10(-8) M. The stimulation of
      PCDGF expression by 17-beta-estradiol was completely inhibited by treatment with
      actinomycin D and with the antiestrogen 4-hydroxytamoxifen. The stimulation of
      PCDGF expression was also demonstrated in another human estrogen-responsive cell
      line T47D. The results presented here provide evidence of a novel estradiol
      responsive gene product in human breast cancer cell lines and give information
      about the hormonal control of epithelin/granulin (PCDGF) expression in these
      cells.

PMID- 10066448
TI  - Multiple infection of TT virus (TTV) with different genotypes in Japanese
      hemophiliacs.
AB  - To clarify the persistent TT virus (TTV) infection, we studied a possibility of
      multiple TTV infection by genotype analysis of isolated TTV obtained from seven
      Japanese hemophiliacs. The nucleotide sequences including 222 bp in the open
      reading frame 1 (ORF1) region of 10 TTV isolates from each patient were analyzed
      and classified into various TTV genotypes such as G1 to G6 by phylogenetic
      analysis using a N-J method. Multiple TTV genotypes were observed in all the
      hemophiliacs: three different TTV genotypes were found in three patients, whereas
      four different TTV genotypes were observed in the other three patients. The
      remaining patient was also infected with TTV of five different genotypes.
      Moreover, new TTV genotypes were found in these seven patients and tentatively
      designated as G7. The present findings indicate that multiple TTV infection with
      different TTV genotypes has occurred in Japanese hemophiliacs. They also provide
      valuable information to understand persistent TTV infection.

PMID- 10066449
TI  - Threshold-dependent DNA synthesis by pure pressure in human aortic smooth muscle
      cells: Gialpha-dependent and -independent pathways.
AB  - Mechanical forces related to pressure and flow are important for the etiology of
      atherosclerosis and hypertension. We hypothesized the presence of mechanosensors
      that were solely sensitive to pure atmospheric pressure in the absence of shear
      and tensile stresses. A pressure-loading apparatus was set up to examine the
      effects of atmospheric pressure on human aortic smooth muscle cells (HASMC).
      Pressure application of 140 to 180 mmHg produced DNA synthesis in a pressure
      dependent manner. In contrast, pressure of 120 mmHg or less produced no
      significant change. Both extracellular signal-regulated kinase and c-Jun N
      terminal kinase activities, but not p38 activity, were stimulated by pressures of
      more than 160 mmHg. Pertussis toxin (PTx) completely inhibited the pressure
      induced increase of DNA synthesis under the high pressure of 200 mmHg. These data
      suggest that HASMC have a mechanosensing cellular switch for DNA synthesis which
      is sensitive to pure atmospheric pressure, and that the molecular switch is
      activated by pressure of more than 140 mmHg. The activation mechanism consists of
      PTx-sensitive and -insensitive pathways, and the former is activated by high pure
      pressure.

PMID- 10066450
TI  - Three splicing variants of tomosyn and identification of their syntaxin-binding
      region.
AB  - We have recently isolated a neural tissue-specific syntaxin-1-binding protein,
      named tomosyn, which is capable of dissociating Munc18/n-Sec1/rbSec1 from
      syntaxin-1 to form a 10S tomosyn complex, an intermediate complex converted to
      the 7S SNARE complex. We isolated here two splicing variants of tomosyn: one had
      36 amino acids (aa) insertion and another had 17 aa deletion. We named original
      one m-tomosyn, big one b-tomosyn, and small one s-tomosyn. s-Tomosyn as well as m
      tomosyn was mainly expressed in brain whereas b-tomosyn was ubiquitously
      expressed. All the isoforms bound to syntaxin-1, but not to syntaxin-2, -3, or 
      4, and had a region highly homologous to VAMP, another syntaxin-binding protein.
      This region was necessary but not sufficient for high-affinity binding of tomosyn
      to syntaxin-1.

PMID- 10066451
TI  - SEA-scFv as a bifunctional antibody: construction of a bacterial expression
      system and its functional analysis.
AB  - A SEA-antibody single chain Fv (SEA-scFv) fusion protein was produced by
      bacterial expression system in this study. SEA-scFv has both staphylococcal
      enterotoxin A (SEA) effects and antibody activity directed at the epithelial
      mucin core protein MUC1, a cancer associated antigen. It was expressed mostly in
      the cytoplasm as an insoluble form. The gene product was solubilized by guanidine
      hydrochloride, refolded by conventional dilution method, and purified using metal
      chelating chromatography. The resulting SEA-scFv fusion protein preparation was
      found to react with MUC1 and MHC class II antigens and had the ability to enhance
      cytotoxicity of lymphokine activated killer cells with a T cell phenotype against
      a human bile duct carcinoma cell line, TFK-1, expressing MUC1. This genetically
      engineered SEA-scFv fusion protein promises to be an important reagent for cancer
      immunotherapy.

PMID- 10066452
TI  - Metabolic properties of normal and mutant mannan-binding proteins in mouse
      plasma.
AB  - Human mannan-binding protein (MBP) is a serum lectin involved in innate immunity.
      MBP activates the complement pathway through its interaction with mannose-rich
      carbohydrates on various microorganisms and a common opsonic defect has been
      shown to be associated with a low serum concentration of MBP. This low serum
      concentration is closely associated with a single base mutation in codon 52, 54
      or 57 of the human MBP gene, which results in a change of Arg52 to Cys, Gly54 to
      Asp, or Gly57 to Gln, respectively, in the collagen-like region of the molecule
      and prevents the formation of higher oligomers. However, the mechanism underlying
      the low serum concentration in such patients is completely unknown. The levels of
      protein synthesis and secretion of the normal and mutant MBPs seem to be similar
      according to our previous in vitro results. In this study, we examined the plasma
      clearance of the normal and mutant human (Gly54Asp) MBPs in mice, and found that
      the half-life of the mutant MBP is about half that of the normal MBP, explaining
      in part the difference in the plasma levels between the two types of MBP.

PMID- 10066453
TI  - Optimisation of electroporation for biochemical experiments in live cells.
AB  - To introduce into cells small molecules, which do not permeate the cell membrane
      naturally, electroporation is the fastest and most efficient technique. Although
      it is not completely benign, the speed at which a full population of cells can be
      permeated gives it a strong advantage over all other cell permeation techniques.
      Here we describe the potential damaging effects of electroporation and how to
      derive conditions which avoid these and assure its use for biochemical
      experiments in live cells.

PMID- 10066454
TI  - Aquaporin-1 expression in proximal tubule epithelial cells of human kidney is
      regulated by hyperosmolarity and contrast agents.
AB  - Primary cells of renal proximal tubule epithelium (S1 segment) of human kidney
      (HRPTE cells) up-regulate aquaporin-1 (AQP-1) expression in response to
      hyperosmolarity. NaCl and D(+)-raffinose increased (2-2.5 fold) AQP-1 expression
      when medium osmolarity was 400 and 500 mOsm/kg.H2O. Urea did not have this
      effect. Unlike our previous findings with mIMCD-3 cells, vasopressin (10(-8)M)
      did not affect AQP-1 expression in HRPTE cells in isosmolar or NaCl-enriched
      hyperosmolar conditions. Furthermore, HRPTE cells increased (3-4 fold) AQP-1
      expression when exposed to hyperosmolar Reno-60 and Hypaque-76 (diatrizoates,
      ionic) contrast agents at 400 and 500 mOsm/kg.H2O. Isosmolar (290 mOsm/kg H2O)
      Visipaque (iodixanol, non-ionic) at 10% (v/v) concentrations also increased AQP-1
      expression, and 25% v/v of Visipaque rendered morphological alterations of HRPTE
      cells and a 3-fold increase in AQP-1 expression after 24h exposure. Finally, semi
      quantitative RT-PCR of HRPTE cells subjected to various isosmolar or hyperosmolar
      conditions demonstrated up-regulation of AQP-1 mRNA and protein levels. Our
      results suggest AQP-1 up-regulation in HRPTE cells exposed to environmental
      stresses such as hyperosmolarity and high doses of isosmolar contrast agents.

PMID- 10066455
TI  - Cloning of a GADD34-like gene that interacts with the zinc-finger transcription
      factor which binds to the p21(WAF) promoter.
AB  - A histone deacetylase inhibitor has been shown to induce differentiation of many
      cancer cells and senescence-like state of human fibroblasts. Previously, our data
      suggested that the region responsive to trichostatin A (TSA), a specific
      inhibitor of histone deacetylase, treatment in the p21(WAF1) promoter is located 
      100 bp upstream from transcription initiation site and contains a GC-box where
      both Sp1 and Sp3 are responsible. Here we show that another zinc-finger
      transcription factor, BFCOL1, which binds to the proximal proalpha2(I) collagen
      promoter, could also bind to this GC-box of the p21 promoter. In addition, we
      cloned a gene whose product interacts with this factor by yeast two-hybrid
      method. The cloned gene was a variant of GADD34 and lacking one PEST region. We
      found that this cDNA product decreased the DNA binding activity of BFCOL1 to the
      GC-rich region of p21 minimal promoter.

PMID- 10066457
TI  - Molecular basis of host-pathogen interaction in septic shock.
AB  - Specific mechanisms of recognition of microbial products have been developed by
      host cells. Among these mechanisms, recognition of lipopolysaccharide of Gram
      negative bacteria by CD14, a glycoprotein expressed at the surface of
      myelomonocytic cells, plays a major role. There is increasing evidence that CD14
      also serves as a receptor for other microbial products including peptidoglycan of
      Gram-positive bacteria. A common theme is that CD14 represents a key molecule in
      innate immunity. Recognition of microbial products by host cells leads to cell
      activation and production of a large array of mediators that are necessary for
      the development of controlled inflammatory processes. When the activation process
      is out of control, such as in septic shock, these mediators can be detrimental to
      the host.

PMID- 10066458
TI  - Enterohemorrhagic Escherichia coli.
AB  - Enterohemorrhagic Escherichia coli has been responsible for an increasing number
      of large food-borne outbreaks of bloody diarrhea and hemolytic uremic syndrome.
      Recent developments in our understanding of the pathogenesis of disease due to
      enterhemorrhagic E. coli include the description of a pathogenicity island, a
      type III secretion system and potential plasmid-encoded virulence factors. Recent
      developments in our understanding of the epidemiology include a recognition of a
      widening spectrum of vehicles.

PMID- 10066459
TI  - The diverse habitats of obligate intracellular parasites.
AB  - Bacterial obligate intracellular parasites have evolved diverse mechanisms for
      evasion of host cellular defenses. These mechanisms involve adaptations for
      survival in distinct intracellular compartments. Intracellular niches inhabited
      by obligate intracellular parasites include the cytoplasm, arrested early
      endosomes, lysosomes, and vesicles that do not fuse with the endosomal
      compartment but intersect with an exocytic pathway.

PMID- 10066460
TI  - Toxins from anaerobic bacteria: specificity and molecular mechanisms of action.
AB  - Major advances have been made in the past five years in the identification of
      cellular targets of toxins produced by anaerobic bacteria. These targets include
      the vesicular membrane docking and fusion apparatus, the actin cytoskeleton, the
      signal transduction machinery and the cell membrane. The recent discovery that
      large clostridial toxins (Clostridium difficile A and B toxins, C. sordellii
      lethal and hemorrhagic toxins, and alpha C. novyi toxin) are
      monoglucosyltransferases, together with the establishment of the perfringolysin
      crystal structure, has led to new insights in the field of toxins from anaerobic
      bacteria.

PMID- 10066461
TI  - Secretion of proteins and assembly of bacterial surface organelles: shared
      pathways of extracellular protein targeting.
AB  - Extracellular or surface localization of virulence determinants is an important
      attribute of pathogenic microorganisms. The past decade has seen significant
      research advances in defining the steps and identifying the necessary machinery
      for protein secretion from bacterial cells. In Gram-negative pathogens, four
      distinct classes of secretion pathways have been identified that deliver
      virulence factors to their sites of action. These pathways are responsible for
      the delivery of soluble extracellular enzymes into the surrounding medium, or for
      specifically targeting proteins to the host cell. In several instances protein
      secretion pathways are similar to those involved in assembly of bacterial
      appendages. Combination of biochemical and genetic analyses has recently revealed
      that the pathways of protein secretion and surface localization of various
      organelles are mechanistically similar which was not apparent simply by comparing
      amino acid sequences of related proteins. The choice of the pathway that a
      protein will utilize may not be dictated only by the specific requirement of the
      secreted protein to traverse the cell envelope in the functional form, but also
      by the need to assure its delivery to the correct site of action outside the
      bacterial cell.

PMID- 10066462
TI  - Oral pathogens: from dental plaque to cardiac disease.
AB  - Oral bacteria exhibit highly specific adherence mechanisms and as a result they
      colonize and cause disease principally in the oral cavity. Oral pathogens,
      however, can produce systemic disease and are known causative agents of infective
      endocarditis. Recent studies have revealed that periodontal disease per se is
      also a statistically significant risk factor for cardiovascular disease. A link
      between the two diseases is the secretion and systemic appearance in
      periodontitis of pro-inflammatory cytokines capable of eliciting effects
      associated with atherosclerosis and coronary heart disease.

PMID- 10066463
TI  - How bacteria initiate inflammation: aspects of the emerging story.
AB  - Recent studies have shown that bacteria possess an array of proinflammatory
      molecules in addition to the extensively studied lipopolysaccharide and
      superantigens. These bacterial molecules include soluble and membrane-associated
      inducers of cytokine release, inducers of host cell apoptosis, and
      immunostimulatory DNA. There is therefore much greater diversity in the class of
      molecules and mechanisms by which bacteria engage the host immune system than
      previously appreciated.

PMID- 10066464
TI  - Vaccination against enteric pathogens: from science to vaccine trials.
AB  - Recent advances in scientific research and clinical trials have shown promise for
      vaccine development against enteric pathogens. Identification of new virulence
      factors, such as the two distinct shigella enterotoxins, has allowed the
      development of new immunogen or new attenuated strains. Improved knowledge
      facilitated the development of safer attenuated live microorganism and
      construction of multivalent vaccines. Finally, an important advantage is the use
      of nonreplicating plasmid DNA vectors to express protective antigens in the host.

PMID- 10066465
TI  - In vivo and ex vivo regulation of bacterial virulence gene expression.
AB  - Bacteria are remarkably adaptable organisms that are able to survive and multiply
      in diverse and sometimes hostile environments. Adaptability is determined by the
      complement of genetic information available to an organism and by the mechanisms
      that control gene expression. In general, gene products conferring a growth or
      survival advantage in a particular situation are expressed, while unnecessary or
      deleterious functions are not. Expression of virulence gene products that allow
      pathogenic bacteria to multiply on and within host cells and tissues are no
      exception to this rule. Being of little or no use to the bacterium except during
      specific stages of the infectious cycle, these accessory factors are nearly
      always subject to tight and coordinate regulation. As a result of recent
      advances, we are beginning to appreciate the complexities of the interactions
      between bacteria and their hosts. The ability to probe virulence gene regulation
      in vivo has broadened our perspectives on pathogenesis.

PMID- 10066466
TI  - Lipid A diversity and the innate host response to bacterial infection.
AB  - Lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria,
      is a potent immunostimulatory molecule which activates the innate host defense
      system. Over the past few years progress has been made in identifying the
      molecular mechanisms of host recognition of lipid A (a component of
      lipopolysaccharide), the identification of the genes required for Escherichia
      coli lipid A biosynthesis, and the role of lipid A acylation when viable bacteria
      are presented to host cells. Recent data indicate that bacteria can regulate this
      molecule in response to different host microenvironments. Host factors that
      induce lipid A modifications and the resultant changes in host response remain to
      be determined.

PMID- 10066467
TI  - Microbial genome sequencing and pathogenesis.
AB  - The year 1997 saw the publication of the complete nucleotide sequence of
      Helicobacter pylori and Escherichia coli. It is conceivable that the complete
      nucleotide sequence for all the major human bacterial pathogens will be available
      by the end of the century. Database alignments have been used to ascribe the
      putative functions of open reading frames in the sequenced isolates and to define
      the differences between bacterial species at the nucleotide level. The most
      striking finding from all genome projects has been the high proportion of open
      reading frames that have no known function. Experimental data demonstrating the
      utility of the genome sequencing projects are only just beginning to emerge.

PMID- 10066468
TI  - Helicobacter pylori: molecular evolution of a bacterial quasi-species.
AB  - Helicobacter pylori persists chronically within individuals and as they spread
      the mutating bacteria migrate with them. The continuous selection and
      microevolution generates a population of closely related but different bacteria
      that behave like a quasi-species. Within this heterogeneity, H. pylori strains
      fall into distinct types, into the virulent (type I) and less virulent (type II)
      strains, based on the presence of a pathogenicity island (cag) that encodes a
      specialized secretion machinery. We propose that during chronic infection a
      dynamic equilibrium between bacteria expressing a disparate degree of virulence
      is established, and that diverse forms prevail at different times.

PMID- 10066469
TI  - Fimbriae-mediated host-pathogen cross-talk.
AB  - Recent studies show that the coupling of fimbrial adhesins of uropathogenic
      Escherichia coli and pathogenic Neisseria species to their complementary
      receptors on host cells is a dynamic event, involving specific signaling to the
      bacteria as well as to the host cell. These studies have unveiled intriguing and
      novel mechanisms by which bacteria utilize their fimbriae to promote virulence at
      the mucosal surface and in deeper tissue.

PMID- 10066470
TI  - Superantigens of gram-positive bacteria: structure-function analyses and their
      implications for biological activity.
AB  - Just as we thought that we know everything about superantigens, new molecular and
      structural studies indicate that we have only just begun to unravel the secrets
      of these fascinating molecules. Recent structure-function analysis of
      superantigens from Gram-positive bacteria, with emphasis on their interaction
      with major histocompatibility complex molecules, could help us decipher the role
      of superantigens in disease, identify host factors that potentiate their effects
      and design drugs that specifically block their activity.

PMID- 10066471
TI  - Epidemiology of emerging/re-emerging antimicrobial-resistant bacterial pathogens.
AB  - The rapid global expansion of bacteria resistant to antimicrobials is the most
      important development over the past year in emerging bacterial diseases. The
      critical events are the emergence of Staphylococcus aureus with decreased
      sensitivity to vancomycin, worldwide resistance to penicillin in Streptococcus
      pneumoniae, and the remorseless progression of multiply-resistant Mycobacterium
      tuberculosis. Most startling was the isolation from a human in Madagascar of a
      plague bacillus possessing a plasmid readily transferable to Escherichia coli,
      which confers multiple antibiotic resistance. The hospital environment continues
      to see the transmission of resistant organisms, notably vancomycin-resistant
      enterococci. Finally, as food markets become more open around the world, food
      borne outbreaks of E. coli O157 and cholera demonstrate how difficult it can be
      to establish effective health and safety barriers.

PMID- 10066472
TI  - Subunits of yeast RNA polymerases: structure and function.
AB  - Following isolation of the genes encoding the putative subunits of RNA polymerase
      in both budding and fission yeasts, combined biochemical and genetic studies,
      together with a structural approach applicable to large assemblies, have begun to
      reveal the protein-protein interactions not only between RNA polymerase subunits
      but also between the RNA polymerases and transcription factors. These protein
      protein interactions ultimately lead to control of the activity and specificity
      of the RNA polymerases.

PMID- 10066473
TI  - Some repressors of bacterial transcription.
AB  - For a long time, repression of transcription in Escherichia coli was thought to
      be generally caused by one repressor binding to one operator. Recent work has
      indicated the frequent presence of auxiliary operators and helper proteins. The
      recent solution of the X-ray structures of Lac and Pur repressors were
      breakthroughs; yet, it has become painfully clear that important aspects of
      repression are still not understood.

PMID- 10066474
TI  - Protein chaperones and the heat shock response in Saccharomyces cerevisiae.
AB  - Recent studies have shed new light on the complexities of the heat shock response
      in yeast. Multiple pathways for transcriptional induction of both classic and
      novel heat shock proteins are emerging together with a more detailed
      understanding of the interactions between protein chaperones and their
      physiological targets. New roles for heat shock proteins in defense and recovery
      from the impacts of thermal stress on critical cellular processes have expanded
      our understanding of these elaborate and ubiquitous proteins.

PMID- 10066475
TI  - Signal transduction by MAP kinase cascades in budding yeast.
AB  - Budding yeast contain at least four distinct MAPK (mitogen activated protein
      kinase) cascades that transduce a variety of intracellular signals: mating
      pheromone response, pseudohyphal/invasive growth, cell wall integrity, and high
      osmolarity adaptation. Although each MAPK cascade contains a conserved set of
      three protein kinases, the upstream activation mechanisms for these cascades are
      diverse, including a trimeric G protein, monomeric small G proteins, and a
      prokaryotic-like two-component system. Recently, it became apparent that there is
      extensive sharing of signaling elements among the MAPK pathways; however, little
      undesirable cross-talk occurs between various cascades. The formation of multi
      protein signaling complexes is probably centrally important for this insulation
      of individual MAPK cascades.

PMID- 10066476
TI  - The Sec system.
AB  - Proteins designated to be secreted by Escherichia coli are synthesized with an
      amino-terminal signal peptide and associate as nascent chains with the export
      specific chaperone SecB. Translocation occurs at a multisubunit membrane-bound
      enzyme termed translocase, which consists of a peripheral preprotein-binding site
      and an ATPase domain termed SecA, a core heterotrimeric integral membrane protein
      complex with SecY, SecE and SecG as subunits, and an accessory integral membrane
      protein complex containing SecD and SecF. Major new insights have been gained
      into the cascade of preprotein targeting events and the enzymatic mechanism or
      preprotein translocation. It has become clear that preproteins are translocated
      in a stepwise fashion involving large nucleotide-induced conformational changes
      of the molecular motor SecA that propels the translocation reaction.

PMID- 10066477
TI  - Positive activation of gene expression.
AB  - Most bacterial transcription activators function by making direct contact with
      RNA polymerase at target promoters. Some activators contact the carboxy-terminal
      domain of the RNA polymerase alpha subunit, some contact region 4 of the sigma70
      subunit, whilst others interact with other contact sites. A number of activators
      are ambidextrous and can, apparently simultaneously, contact more than one target
      site on RNA polymerase. Expression from many promoters is co-dependent on two or
      more activators. There are several different mechanisms for coupling promoter
      activity to more than one activator: in one such mechanism, the different
      activators make independent contacts with different target sites on RNA
      polymerase.

PMID- 10066478
TI  - Proteolysis and chaperones: the destruction/reconstruction dilemma.
AB  - Cytoplasmic proteases, although necessary for proper cell functioning, must be
      strictly regulated. In fact, they resemble chaperones, ancient protein folding
      devices. These molecules recognise exposed hydrophobic regions of unfolded or
      denatured proteins. For most substances it is not known how the cell chooses
      between the refolding and proteolytic pathways. In Escherichia coli, however, a
      carboxy-terminal proteolysis tag and binding site for the chaperone DnaK have
      recently been identified.

PMID- 10066479
TI  - Mechanisms of solute transport through outer membrane porins: burning down the
      house.
AB  - Porins mediate the uptake of nutrients across the outer membrane of Gram-negative
      bacteria. For general porins like OmpF, electrophysicoloigcal experiments now
      establish that the charged residues within their channels primarily modulate pore
      selectivity, rather than voltage-gated switching between open and closed states.
      Recent studies on the maltoporin, LamB, solidify the importance of its 'greasy
      slide' aromatic residues during sugar transport, and suggest the involvement of
      L9, in the exterior vestibule, as the initial maltodextrin binding site. The
      application of biophysical methodologies to the TonB-dependent porin, FepA,
      ostensibly reveal the opening and closing of its channel during ligand uptake, a
      phenomenon that was predicted but not previously demonstrated.

PMID- 10066480
TI  - Bacterial solute uptake and efflux systems.
AB  - The recent discovery of binding protein dependent secondary transporters and the
      ever-growing family of membrane potential generating secondary transporters
      emphasize the diversity of transport systems in both the mechanistical and
      physiological sense. The vast amount of data on the lactose permease is now
      beginning to crystallize in a model that relates functional events to structural
      changes of the protein. Evidence has been presented that multidrug transporters
      pick up their substrates from the membrane, and the binding of a number of
      substrates to the binding-protein components of ATP-driven transporters is now
      understood in detail.

PMID- 10066481
TI  - The regulation of bacterial cell division: a time and place for it.
AB  - Temporal and spatial regulation of cell division assures that each daughter cell
      receives a copy of the chromosome. Within the past year, the application of
      fluorescence microscopy to the cell biology of bacteria has revealed an
      increasing number of proteins that are localized within the bacterial cell to
      carry out DNA segregation and cell division. The localization of these proteins
      implies the existence of positional information in the cell, but how this
      information is established is unknown.

PMID- 10066482
TI  - The chaperone/usher pathway: a major terminal branch of the general secretory
      pathway.
AB  - Gram-negative bacteria assemble a variety of adhesive organelles on their
      surface, including the thread-like structures known as pili. Recent studies on
      pilus assembly by the chaperone/usher pathway have revealed new insights into the
      mechanisms of pilus subunit export into the periplasm and targeting to the outer
      membrane. Signaling events controlling pilus biogenesis have begun to emerge and
      investigations of the usher have yielded insights into pilus translocation across
      the outer membrane.

PMID- 10066483
TI  - Signal transduction in bacteria: molecular mechanisms of stimulus-response
      coupling.
AB  - In bacteria, adaptive responses to changing environmental conditions are mediated
      by signal transduction systems that involve modular protein domains. Despite
      great diversity in the integration of domains into different systems, studies of
      individual components have revealed molecular strategies that are widely
      applicable. Studies of receptors have advanced our understanding of how
      information is transmitted across membranes, the determination of three
      dimensional structures of domains of histidine protein kinase domains and
      response regulator proteins has begun to reveal the molecular basis of signaling
      via two-component phosphoryltransfer pathways, and the description of 'eukaryotic
      like' protein domains involved in bacterial signaling has emphasized the
      universality of intracellular signaling mechanisms.

PMID- 10066484
TI  - Initiation of bacterial development.
AB  - The discovery of a mitotic apparatus in bacteria has led to significant recent
      progress being made in understanding the regulatory connections between the cell
      cycle, chromosome segregation and the onset of developmental processes in
      sporulation. The control of developmental transcription by antagonism between
      protein kinase and protein phosphatase reached a new level of complexity with the
      discovery of peptide inhibitors of protein phosphatases that cycle between the
      interior and exterior cell surface as information messengers. New mechanisms of
      developmental regulation are being uncovered in a variety of microbial systems.

PMID- 10066485
TI  - Self perception in bacteria: quorum sensing with acylated homoserine lactones.
AB  - A variety of Gram-negative bacteria produce membrane permeant, acylated
      homoserine lactone (HL) pheromones that act as cell density cues. Synthesis and
      response to these factors requires proteins homologous to the Luxl acylhomoserine
      lactone synthase and the LuxR transcription factor from Vibrio fischeri. Recent
      genetic and biochemical studies have begun to provide a mechanistic understanding
      of acyl HL dependent gene regulation. Examination of the role of acyl HLs in
      diverse bacteria positions LuxR-Luxl type systems within an increasingly broad
      regulatory context and suggests that, in some bacteria, they comprise a global
      regulatory circuit.

PMID- 10066486
TI  - Peroxisome biogenesis: from yeast to man.
AB  - A major current issue in studies of peroxisome biogenesis is how proteins are
      imported into the organelle or inserted into its membrane. Recent studies
      indicate that these two processes use independent pathways. Both appear to have
      unexpected properties. Matrix proteins can be imported in an oligomeric form
      which might be facilitated by cycling receptors, whereas insertion of at least
      some peroxisomal membrane proteins seems to involve the endoplasmic reticulum.

PMID- 10066487
TI  - In situ methods for assessment of microorganisms and their activities.
AB  - Recent technical developments in the field of molecular biology and microsensors
      are beginning to enable microbiologists to study the abundance, localization and
      activity of microorganisms in situ. The various new methods on their own bear
      high potential but it is the combination of studies on structure and function of
      microbial communities that will yield the most detailed insights in the way
      microorganisms operate in nature.

PMID- 10066488
TI  - A natural species concept for prokaryotes.
AB  - Direct molecular analyses of natural microbial populations reveal patterns that
      should compel microbiologists to adopt a more natural species concept that has
      been known to biologists for decades. The species debate can be exploited to
      address a larger issue - microbiologists need, in general, to take a more natural
      view of the organisms they study.

PMID- 10066489
TI  - Structure and function of anthropogenically altered microbial communities in
      coastal waters.
AB  - Human-based (anthropogenic) nutrient and other pollutant enrichment of the
      world's coastal waters is causing unprecedented changes in microbial community
      structure and function. Symptoms of these changes include accelerating
      eutrophication, the proliferation of harmful microalgal blooms, excessive oxygen
      consumption (hypoxia, anoxia), increasing toxicity, altered routes and fluxes of
      organic and inorganic matter cycling, and disruption of food webs. Biogeochemical
      and trophic consequences are expanding on local, regional and global scales.

PMID- 10066490
TI  - Genomics and computational molecular biology.
AB  - There has been a dramatic increase in the number of completely sequenced
      bacterial genomes during the past two years as a result of the efforts both of
      public genome agencies and the pharmaceutical industry. The availability of
      completely sequenced genomes permits more systematic analyses of genes, evolution
      and genome function than was otherwise possible. Using computational methods -
      which are used to identify genes and their functions including statistics,
      sequence similarity, motifs, profiles, protein folds and probabilistic models -
      it is possible to develop characteristic genome signatures, assign functions to
      genes, identify pathogenic genes, identify metabolic pathways, develop diagnostic
      probes and discover potential drug-binding sites. All of these directions are
      critical to understanding bacterial growth, pathogenicity and host-pathogen
      interactions.

PMID- 10066491
TI  - Expression systems and physiological control of promoter activity in bacteria.
AB  - Promoter activity in vivo is not just dependent on the performance of the
      regulator/promoter pair which may predominantly control transcription initiation
      in response to a given signal, it also relies on overimposed mechanisms that
      connect the activity of individual promoters to the metabolic and energetic
      status of the bacterial cells. Such mechanisms - which frequently become limiting
      for biotechnological applications involving regulated promoters - include classic
      (i.e. cAMP/CRP-mediated) or alternative catabolite control checks, recruitment of
      protein intermediates of the phosphotransferase sugar transport system,
      coregulation through protein-induced DNA bending and the interplay of sigma
      factors during various growth stages.

PMID- 10066492
TI  - The evolution of biotransformation technologies.
AB  - Biotransformation is a broad and growing field of biotechnology and encompasses
      both enzymatic and microbial biocatalysis. Progress has been made in research on
      the key drivers of biotransformations, including the isolation and
      characterization of microbes and their enzymes from, and their utilization in,
      extreme environments, the manipulation, alteration, and augmentation of metabolic
      pathways, and the use of combinatorial biosynthesis and biocatalytic
      methodologies for new compound development.

PMID- 10066493
TI  - What's up down there?
AB  - The development of careful quality assurance criteria assuring freedom from
      contamination in all aspects of sample recovery has opened the window to studies
      of a fascinating new microbial biome in the deep subsurface. Organisms have been
      recovered with unusual metabolic capabilities and a chemosynthetic lifestyle
      independent of the recent surface photosynthetically derived energy inputs. The
      properties of the subsurface microbiota are critical when assessing aspects such
      as the utility of burying radioactive waste, the remediation of mixtures of
      organics, metals, and nuclides, and the search for life in extreme environments
      on Earth as well as on Mars and other extraterrestrial sites. In addition this
      pioneering work provides a foundation for examining life processes in extreme
      environments, such as the environment beneath the ocean floor.

PMID- 10066494
TI  - The role of metabolic engineering in the production of secondary metabolites.
AB  - In the production of secondary metabolites yield and productivity are the most
      important design parameters. The focus is therefore to direct the carbon fluxes
      towards the product of interest, and this can be obtained through metabolic
      engineering whereby directed genetic changes are introduced into the production
      strain. In this process it is, however, important to analyze the metabolic
      network through measurement of the intracellular metabolites and the flux
      distributions. Besides playing an important role in the optimization of existing
      processes, metabolic engineering also offers the possibility to construct strains
      that produce novel metabolites, either through the recruitment of heterologous
      enzyme activities or through introduction of specific mutations in catalytic
      activities.

PMID- 10066495
TI  - Flow cytometry and bacterial pathogenesis.
AB  - Our understanding of microbial adaptations to diverse and threatening
      environments is limited by the assumption that the behavior of individual
      bacteria can be accurately determined by measuring the behavior of populations.
      Recent advances in gene expression reporter systems, fluorescence microscopy and
      flow cytometry allow microbiologists to explore the complex interactions between
      bacteria and their environment with single cell resolution. The application of
      these technologies has been particularly useful in systems, such as host-pathogen
      interactions, where genetic analysis is often cumbersome. Recently, flow
      cytometry is increasingly being applied to study host-pathogen interactions.

PMID- 10066496
TI  - Barophiles: deep-sea microorganisms adapted to an extreme environment.
AB  - The deep-sea environment is characterized by high pressure and low temperature
      but in the vicinity of hydrothermal vents regions of extremely high temperature
      exist. Deep-sea microorganisms have specially adapted features that enable them
      to live and grow in this extreme environment. Recent research on the physiology
      and molecular biology of deep-sea barophilic bacteria has identified pressure
      regulated operons and shown that microbial growth is influenced by the
      relationship between temperature and pressure in the deep-sea environment.

PMID- 10066497
TI  - Imaging techniques in microbiology.
AB  - Recent advances in optical imaging have dramatically expanded the capabilities of
      the light microscope and its usefulness in microbiology research. Some of these
      advances include improved fluorescent probes, better cameras, new techniques such
      as confocal and deconvolution microscopy, and the use of computers in imaging and
      image analysis. These new technologies have now been applied to microbiological
      problems with resounding success.

PMID- 10066498
TI  - Combinatorial biosynthesis for new drug discovery.
AB  - Combinatorial biosynthesis involves interchanging secondary metabolism genes
      between antibiotic-producing microorganisms to create unnatural gene combinations
      or hybrid genes if only part of a gene is exchanged. Novel metabolites can be
      made by both approaches, due to the effect of a new enzyme on a metabolic pathway
      or to the formation of proteins with new enzymatic properties. The method has
      been particularly successful with polyketide synthase (PKS) genes: derivatives of
      medically important macrolide antibiotics and unusual polycyclic aromatic
      compounds have been produced by novel combinations of the type I and type II PKS
      genes, respectively. Recent extensions of the approach to include deoxysugar
      biosynthesis genes have expanded the possibilities for making new microbial
      metabolites and discovering valuable drugs through the genetic engineering of
      bacteria.

PMID- 10066500
TI  - Strange bedfellows.

PMID- 10066499
TI  - The value of microbial diversity.
AB  - In the past few years, due to the use of molecular methods, our knowledge of
      microbial diversity has increased dramatically, not only from a phylogenetic and
      taxonomic perspective but also from an ecological basis. We now know that
      microorganisms exist in every conceivable place on Earth, even in extreme
      environments. Temperature may be the only limitation as to where they can and
      cannot exist and/or function. As more small subunit rDNA sequence information
      becomes available there is a real need to start turning the information into
      knowledge that can be applied to better elucidate and understand structure
      function relationships within ecosystems, develop new culturing methods, and
      discover new products and processes. It has been stated on numerous occasions
      that the 21(st) century is the century for biology. Within that context, we must
      address the real value of microbial diversity.

PMID- 10066501
TI  - Microbiology.

PMID- 10066502
TI  - Molecular and cellular microbiology: new tools of the trade.

PMID- 10066503
TI  - Web alert. Ecology and industrial microbiology techniques.

PMID- 10066504
TI  - Viral persistence: mechanisms and consequences.
AB  - Recent research has brought additional information on how virus products
      interfere with host cell antigen processing in vitro, new information on the
      interaction of virus with dendritic cells as a mechanism for alteration of immune
      responses - especially immunosuppression, and a preliminary proposal that
      nonretroviral RNA viruses might persist by utilizing host-cell reverse
      transcriptase to enter a DNA phase of replication.

PMID- 10066505
TI  - Surface coats and secretory trafficking in African trypanosomes.
AB  - Recent advances in transfection technology have been exploited to address
      fundamental questions relating to secretory trafficking in African trypanosomes.
      Targeted gene disruptions and ectopic expression of the major stage-specific
      surface proteins have provided unexpected insights into both the function and
      assembly of the essential parasite surface coats. A growing list of novel
      secretory cargo molecules, as well as advances in the characterization of
      trypanosomal secretory machinery, provide a unique model system for the study of
      eukaryotic secretory processes.

PMID- 10066506
TI  - Herpes simplex virus latency and the immune response.
AB  - Following infection, herpes simplex virus establishes latency in the nervous
      system and recurrences of lytic replication occur periodically. Molecular events
      which may determine how virus enters latency, how it is maintained and what
      occurs during reactivation have been investigated. The role of the immune
      response in limiting infection of the nervous system, influencing the latent
      state and removing virus from peripheral sites following reactivation has also
      been studied.

PMID- 10066507
TI  - The new numerology of immunity mediated by virus-specific CD8(+) T cells.
AB  - Our understanding of virus-specific CD8(+) T cell responses is currently being
      revolutionized by peptide-based assay systems that allow flow cytometric analysis
      of effector and memory cytotoxic T lymphocyte populations. These techniques are,
      for the first time, putting the analysis of T-cell-mediated immunity on a
      quantitative basis.

PMID- 10066508
TI  - Reporters for the analysis of gene regulation in fungi pathogenic to man.
AB  - In the past few years, highly sensitive gene reporters have been developed for
      the infectious fungi including gene reporters with altered codon usage. The tools
      are, therefore, now at hand for functionally characterizing the promoters of
      genes regulated by the bud-hypha transition, high frequency switching and cues
      from the cellular environment.

PMID- 10066509
TI  - Insertional mutagenesis of pathogenic fungi.
AB  - Screening insertional mutants for loss of virulence is an effective method for
      investigating the molecular genetic basis of bacterial pathogenesis, but has only
      recently been applied to fungal pathogens. For many pathogenic fungi
      transformation with heterologous plasmid DNA results in complex integration
      events. This problem can now be circumvented for some species using restriction
      enzyme mediated integration. Insertional mutagenesis of Fusarium oxysporum using
      the naturally occurring fungal transposon impala has been described, but
      transposon tagging for other fungi has yet to be developed. Although insertional
      mutagenesis has recently identified important virulence determinants of fungal
      phytopathogens, the lack of suitable screening strategies has so far limited its
      applicability for fungal pathogens of humans.

PMID- 10066510
TI  - Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite
      interactions.
AB  - Trypanosomes and Leishmania contain an abundance of stage-regulated cysteine
      proteinases encoded by several gene families. Analysis of parasites rendered
      defective in cysteine proteinase function, either through genetic manipulation or
      through the use of specific inhibitors, has revealed roles for the enzymes in
      parasite virulence, in modulation of the host's immune response and in parasite
      differentiation.

PMID- 10066511
TI  - Gene disruption to evaluate the role of fungal candidate virulence genes.
AB  - Gene disruption is a powerful genetic tool that can define pathogenic or
      virulence factors. In the past two years gene disruption approaches have been
      used to identify fungal virulence genes. The capsule genes, an alpha subunit of G
      protein and certain kinases of Cryptococcus neoformans have clearly been
      demonstrated to be associated with pathogenicity. In Candida albicans at least
      four genes involved in hyphal formation have been disrupted and tested for
      virulence. In other fungi, such as Histoplasma capsulatum, however, more
      efficient gene disruption methods need to be developed before such approaches can
      be regularly used for identifying virulence genes.

PMID- 10066512
TI  - Adhesive proteins of the malaria parasite.
AB  - Malaria infection of the host cells requires host-parasite recognition events
      mediated by adhesion and signaling molecules. Recent development of systems for
      stable transformation and targeted integration of exogenous DNA in malaria
      parasites provides a powerful tool to study the structure and function of
      Plasmodium attachment motifs, and their role in infection and disease.

PMID- 10066513
TI  - Signaling and host cell invasion by Trypanosoma cruzi.
AB  - Signal transduction events triggered in mammalian host cells by the obligate
      intracellular parasite Trypanosoma cruzi are required for invasion. Infective T.
      cruzi trypomastigotes elicit Ca2+ signaling in mammalian host cells and activate
      transforming growth factor-beta receptor signaling pathways. The elevation of
      Ca2+ in T. cruzi, induced by host-cell contact, is also required for invasion,
      extending the concept of host-pathogen 'cross-talk' to invasive protozoan
      pathogens.

PMID- 10066514
TI  - Genetic analysis in fungi using restriction-enzyme-mediated integration.
AB  - Restriction-enzyme-mediated integration (REMI), a method for generating
      nonhomologous integration of transforming DNA into the chromosomes of eukaryotic
      cells, has been used for insertion mutagenesis and other genetic studies in
      diverse organisms. Insertion mutations generated by REMI have facilitated the
      genetic dissection of developmental pathways in Dictyostelium discoidium and the
      isolation of virulence factors in several plant pathogenic fungi. Recent work
      indicates that REMI occurs by nonhomologous end joining.

PMID- 10066515
TI  - Transmissible spongiform encephalopathies: transmission, mechanism of disease,
      and persistence.
AB  - Prion protein is central to the control of development of all transmissible
      spongiform encephalopathies. Controversy exists as to whether the protein itself
      is responsible for disease manifestation, in one of perhaps several isoforms, or
      whether an additional informational molecule must be involved in conjunction with
      the protein. Recent studies have been trying to resolve these issues.

PMID- 10066516
TI  - Green fluorescent protein as a reporter of transcription and protein localization
      in fungi.
AB  - Green fluorescent protein (GFP) is a versatile and powerful tool for analysis of
      diverse biological processes. The recent development of GFP variants with altered
      spectral properties and altered codon composition has allowed efficient
      expression of GFP in a number of fungal species. GFP has been successfully used
      to analyze transcription regulation as well as protein and organelle
      localization, and promises to give an unprecedented view into the dynamic
      subcellular processes that shape the fungal cell.

PMID- 10066517
TI  - Cytokine responses in virus infections: effects on pathogenesis, recovery and
      persistence.
AB  - During the past year, significant advances have been made in our understanding of
      cytokine regulation and the respective roles played by T helper cells type 1 and
      2 immune responses during virus infection. Numerous mechanisms by which viruses
      may evade host immune defences have now been identified, some directly
      influencing cytokine activity. Major advances have also been made in delineating
      the roles of cytokines and chemokines at different stages in the pathogenesis of
      HIV infection.

PMID- 10066518
TI  - Intracellular trafficking in Plasmodium-infected erythrocytes.
AB  - The past few years have witnessed considerable progress in molecular and
      biochemical studies of intracellular trafficking in malaria-infected red cells.
      Highlights include the identification of solute channels in the vacuolar membrane
      and the red blood cell membrane, a tubovesicular membrane network that delivers
      exogenous nutrients and drugs to the parasite, and parasite gene families that
      mediate adherence to endothelial cells and red cells.

PMID- 10066519
TI  - HIV pathogenesis: mechanisms of susceptibility and disease progression.
AB  - The understanding of the factors associated with HIV-1 acquisition and disease
      progression has been significantly advanced in the past few years. These factors
      can be broadly defined as intrinsic or acquired and are operative at the levels
      of disease acquisition and progression or both. Much recent attention has focused
      on the identification of allelic variants at specific genetic loci that alter
      either susceptibility to infection or the natural history of disease progression.
      In addition, a more detailed understanding of the immunologic responses to HIV-1
      and factors that perturb these responses has greatly enhanced our understanding
      of the immunologic control of HIV-1 and the roles of cofactors in HIV-1
      acquisition and disease progression.

PMID- 10066520
TI  - Vaccination against enteric pathogens: from science to vaccine trials.

PMID- 10066521
TI  - Rates and patterns of chromosome evolution in enteric bacteria.
AB  - Although several types of large-scale alterations potentially affect the
      structure and organization of bacterial genomes, recent analyses of physical maps
      and complete genomic sequences reveal that chromosome heterogeneity in enteric
      bacteria has resulted from the acquisition and deletion of large segments of DNA.
      These acquired sequences can provide novel functions immediately upon their
      introduction and play a significant role in the diversification of bacterial
      species.

PMID- 10066522
TI  - Global dinucleotide signatures and analysis of genomic heterogeneity.
AB  - Early biochemical experiments measuring nearest neighbor frequencies established
      that the set of dinucleotide relative abundance values (dinucleotide biases) is a
      remarkably stable property of the DNA of an organism. Analyses of currently
      available genomic sequence data have extended these earlier results, showing that
      the dinucleotide biases evaluated for successive 50 kb segments of a genome are
      significantly more similar to each other than to those of sequences from more
      distant organisms. From this perspective, the set of dinucleotide biases
      constitutes a 'genomic signature' that can discriminate sequences from different
      organisms. The dinucleotide biases appear to reflect species-specific properties
      of DNA stacking energies, modification, replication, and repair mechanisms. The
      genomic signature is useful for detecting pathogenicity islands in bacterial
      genomes.

PMID- 10066523
TI  - Research and development of antibacterial agents.
AB  - Several new antibacterial agents are currently being developed in response to the
      emergence of bacterial resistance to existing drugs. The new agents include
      compounds that inhibit macromolecular synthesis or interfere with bacterial
      membrane function. Apart from the oxazolidinones and cationic peptides, the
      remainder of these new compounds are analogues of earlier antibiotic classes;
      therefore, it is probable that existing resistance mechanisms will adapt to
      accommodate the new derivatives. To minimise the potential for emergence of
      resistance to new agents, research strategies should be chosen that not only
      enhance the discovery of structurally novel drugs, but also direct these to new
      molecular targets that may themselves have decreased potential to give rise to
      drug-resistant variants.

PMID- 10066524
TI  - New antibiotic discovery, novel screens, novel targets and impact of microbial
      genomics.
AB  - The clinical need for new classes of antibiotic continues to grow, as drug
      resistance erodes the efficacy of current therapies. Historically, most
      antibiotics were discovered by random screening campaigns, but over the past 20
      years, this strategy has largely failed to deliver a sufficient range of chemical
      diversity to keep pace with changing clinical profiles. A more rational approach
      to drug hunting has been greatly potentiated by the availability of bacterial
      genomic information. The rapid progress in sequencing and analysis of these
      small, prokaryotic genomes has enabled the concomitant development of powerful
      new technologies that are already enhancing the potential utility of genomic
      information. The future promises versatile and precise tools to understand what
      makes a successful antibiotic and moreover the means to identify and evaluate
      novel classes of drug.

PMID- 10066525
TI  - Multiple antibiotic resistance and efflux.
AB  - Multiple antibiotic resistance in bacteria was at first thought to be caused
      exclusively by the combination of several resistance genes, each coding for
      resistance to a single drug. More recently, it became clear that such phenotypes
      are often achieved by the activity of drug efflux pumps. Some of these efflux
      pumps exhibit an extremely wide specificity covering practically all antibiotics,
      chemotherapeutic agents, detergents, dyes, and other inhibitors, the exception
      perhaps being very hydrophilic compounds. Such efflux pumps work with exceptional
      efficiency in Gram-negative bacteria through their synergistic interaction with
      the outer membrane barrier. It is disturbing that the antibacterial agents of the
      most advanced type, which are unaffected by common resistance mechanisms, are
      precisely the compounds whose use appears to select for multidrug-resistant
      mutants that overproduce these efflux pumps of wide specificity.

PMID- 10066526
TI  - Bacterial genomics and adaptation to life on plants: implications for the
      evolution of pathogenicity and symbiosis.
AB  - Many bacteria form intimate associations with plants. Despite the agricultural
      and biotechnological significance of these bacteria, no whole genome sequences
      have yet been described. Plant-associated bacteria form a phylogenetically
      diverse group, with representative species from many major taxons. Sequence
      information from genomes of closely related bacteria, in combination with
      technological developments in the field of functional genomics, provides new
      opportunities for determining the origin and evolution of traits that contribute
      to bacterial fitness and interactions with plant hosts.

PMID- 10066527
TI  - New antivirals - mechanism of action and resistance development.
AB  - In recent years, several novel treatment modalities emerged for a number of virus
      infections, including lamivudine for hepatitis B virus, abacavir, adefovir
      dipivoxyl and apropovir disprometil for human immunodeficiency virus, cidofovir
      for cytomegalovirus, and famciclovir (the oral prodrug of penciclovir) and
      cidofovir for other herpesviruses (i.e. herpes simplex virus and varicella-zoster
      virus). For all drugs, resistance eventually develops upon prolonged
      administration to the infected individuals, albeit at a varying extent. In
      addition, new mutations related to multidrug resistance have recently been
      identified.

PMID- 10066528
TI  - Comparative mycobacterial genomics.
AB  - Genomics is providing us with a mass of information about the biochemistry,
      physiology and pathogenesis of Mycobacterium tuberculosis and Mycobacterium
      leprae. Comparison of the two genome sequences is mutually enriching and
      indicates that the M. leprae genome appears to have undergone shrinkage and large
      scale gene inactivation, which may account for the exceptionally slow growth of
      this organism.

PMID- 10066529
TI  - Mycoplasma pneumoniae and Mycoplasma genitalium: a comparison of two closely
      related bacterial species.
AB  - The rapid progress in sequencing large quantities of DNA will provide an
      increasing number of complete genome sequences of closely related bacterial
      species as well as of pairs of isolates from the same species with different
      features, such as a pathogenic and an apathogenic representative. This opens the
      way to apply subtractive comparative analysis as a tool to select from the large
      pool of all bacterial genes a relatively small set of genes that can be
      correlated with the expression of a certain phenotype. These selected genes can
      then be the target for further functional analyses.

PMID- 10066530
TI  - Antibacterials - mechanisms of action.
AB  - Recent studies on antibacterials have focused on the development of
      antimycobacterial agents and antibacterial peptides, and on furthering the
      understanding of agents that have been available for several decades, including
      imidazoles, beta-lactams and quinolones. New areas of research include antisense
      oligonucleotides, antibacterial peptides and a new class of agents,
      oxazolidinones.

PMID- 10066531
TI  - The superbugs: evolution, dissemination and fitness.
AB  - Since the introduction of antibiotics, bacteria have not only evolved elegant
      resistance mechanisms to thwart their effect, but have also evolved ways in which
      to disseminate themselves or their resistance genes to other susceptible
      bacteria. During the past few years, research has revealed not only how such
      resistance mechanisms have been able to evolve and to rapidly disseminate, but
      also how bacteria have, in some cases, been able to adapt to this new burden of
      resistance with little or no cost to their fitness. Such adaptations make the
      control of these superbugs all the more difficult.

PMID- 10066532
TI  - Bacterial enzymatic resistance: beta-lactamases and aminoglycoside-modifying
      enzymes.
AB  - Numerous novel beta-lactamases and aminoglycoside-modifying enzymes with altered
      substrate profiles continue to be identified. Plasmid-mediated transmission of
      many of these enzymes readily occurs due to inclusion of the encoding genes in
      mobile gene cassettes. Recent crystallographic determinations of the structures
      of metallo-beta-lactamases and aminoglycoside-modifying enzymes provide the
      opportunity for the rational design of inhibitors.

PMID- 10066533
TI  - Antifungals: mechanism of action and resistance, established and novel drugs.
AB  - Serious fungal infections, caused mostly by opportunistic species, are
      increasingly common in immunocompromised and other vulnerable patients. The use
      of antifungal drugs, primarily azoles and polyenes, has increased in parallel.
      Yet, established agents do not satisfy the medical need completely: azoles are
      fungistatic and vulnerable to resistance, whereas polyenes cause serious host
      toxicity. Drugs in clinical development include echinocandins, pneumocandins, and
      improved azoles. Promising novel agents in preclinical development include
      several inhibitors of fungal protein, lipid and cell wall syntheses. Recent
      advances in fungal genomics, combinatorial chemistry, and high-throughput
      screening may accelerate the antifungal discovery process.

PMID- 10066534
TI  - Sulfolobus genome: from genomics to biology.
AB  - Major progress in sequencing the genome of Sulfolobus solfataricus has been
      closely concerted with the characterization and sequencing of many
      extrachromosomal genetic elements, including viruses, cryptic plasmids and
      conjugative plasmids, as well as mobile archaeal introns and transposons. The
      latter have provided a basis for developing the first generation of vectors that
      are now being used to study the genetics of Sulfolobus and other Archaea.

PMID- 10066536
TI  - Two-component signal transduction systems in eukaryotic microorganisms.
AB  - Conserved signal transduction pathways that use phosphorelay from histidine
      kinases through an intermediate transfer protein (H2) to response regulators have
      been found in a variety of eukaryotic microorganisms. Several of these pathways
      are linked to mitogen-activated protein kinase cascades. These networks control
      different physiological responses including osmoregulation, cAMP levels and
      cellular morphogenesis.

PMID- 10066537
TI  - The threat of bioterrorism returns the fear of smallpox.

PMID- 10066538
TI  - Initiation of aerial mycelium formation in Streptomyces.
AB  - In the past two years, the isolation of extracellular factors involved in the
      initiation of aerial mycelium formation, the identification of metabolic defects
      in certain developmental mutants, and the characterisation of three further bld
      genes and several gamma-butyrolactone receptor genes have led to new ideas about
      the mechanisms that initiate aerial mycelium formation in Streptomyces. The
      emerging picture suggests the integration of numerous signals from both inside
      and outside the cell.

PMID- 10066539
TI  - Dimorphism and virulence in Candida albicans.
AB  - Two regulatory pathways govern filamentation in the pathogenic fungus Candida
      albicans. Recent virulence studies of filamentation regulatory mutants argue that
      both yeast and filamentous forms have roles in infection. Filamentation control
      pathways seem closely related in C. albicans and in Saccharomyces cerevisiae,
      thus permitting speculation about C. albicans filamentation genes not yet
      discovered.

PMID- 10066540
TI  - Cell cycle and sporulation in Bacillus subtilis.
AB  - Recent work on cell division and chromosome orientation and partitioning in
      Bacillus subtilis has provided insights into cell cycle regulation during growth
      and development. The cell cycle is an integral part of development and entrance
      into sporulation is modulated by signals that transmit the status of DNA
      integrity, chromosome replication and segregation. In addition, B. subtilis
      modifies cell division and DNA segregation to establish cell-type-specific gene
      expression during sporulation.

PMID- 10066541
TI  - Polarity and division site specification in yeast.
AB  - A significant component of polarization in budding yeast involves the regulated
      restructuring of the actin cytoskeleton in response to defined cellular signals.
      Recent evidence suggests that such cytoskeletal organization arises through the
      action of large protein complexes that form in response to signals from small GTP
      binding proteins, such as Cdc42, Rho, and Ras. These actin-organizing complexes
      may be fairly diverse, but generally consist of one or more central scaffold
      proteins, such as those of the formin class, that bind to signaling molecules and
      recruit actin-binding proteins to bring about desired polarizing events.

PMID- 10066542
TI  - Vicious circles: a mechanism for yeast aging.
AB  - The past year has confirmed the great potential of the yeast Saccharomyces
      cerevisiae as a model to study aging. Ground breaking papers have revealed
      similarities between aging in yeast and in mammals, and have identified genetic
      instability of the ribosomal DNA array as the first known cause of aging in yeast
      cells.

PMID- 10066543
TI  - Protein localization during the Caulobacter crescentus cell cycle.
AB  - New research on bacterial cells has demonstrated that they have a dynamic and
      complex subcellular organization. Work in Caulobacter crescentus shows that
      essential and nonessential proteins localize to discrete positions in the cell as
      a function of cell-cycle progression. The flagellum and chemotaxis receptor are
      asymmetrically localized to a single pole in the predivisional cell by
      coordinated proteolysis and transcriptional regulation. Cell type- and
      compartment-specific localization of the CtrA global transcriptional regulator is
      essential for proper cell-cycle progression, and subcellular localization of key
      chromosome partitioning proteins is correlated with proper nucleoid segregation.
      Given this structural complexity, we are driven to ask how localization is
      achieved, and to what end.

PMID- 10066544
TI  - Infection-related development in the rice blast fungus Magnaporthe grisea.
AB  - Recent developments have been made in the identification of signal transduction
      pathways and gene products involved in the infection-related development of the
      rice blast fungus, Magnaporthe grisea. It has been established that cAMP
      dependent and MAP kinase-mediated signaling are both critical for appressorium
      morphogenesis and function. These signaling pathways may act downstream of
      hydrophobin-mediated surface sensing by the growing germ tube. Several genes have
      been identified that are required for invasive growth of M. grisea including
      genes that allow adaptation of fungal metabolism to growth within plant tissues.

PMID- 10066545
TI  - The cyanobacterial circadian system: a clock apart.
AB  - Several new molecular components of the circadian clocks of animals, fungi, and
      bacteria have been unveiled in the past two years. Enough parts are now
      identified to indicate that there is more than one way to build a biological
      clock, although there are parallels in the cycling molecular events among
      disparate groups of organisms.

PMID- 10066546
TI  - Heterocyst formation in Anabaena.
AB  - Heterocystous cyanobacteria grow as multicellular organisms with a distinct one
      dimensional developmental pattern of single nitrogen-fixing heterocysts separated
      by approximately ten vegetative cells. Several genes have been identified that
      are required for heterocyst development and pattern formation. A key regulator,
      HetR, has been recently shown to be aserine-type protease.

PMID- 10066547
TI  - Assembly of the VirB transport complex for DNA transfer from Agrobacterium
      tumefaciens to plant cells.
AB  - The VirB transporter is a type IV secretion system that mediates the genetic
      transformation of plant cells by Agrobacterium tumefaciens. Assembly of this
      transporter depends on, first, formation of a VirB7/B9 complex that stabilizes
      many of the VirB proteins, second, formation of a virulence-specific pilus
      composed primarily of VirB2 and VirB5, and, third, post-translational processing
      of VirB1 and VirB2.

PMID- 10066548
TI  - On growth and form: control of cell morphogenesis in fission yeast.
AB  - In the past year, we have gained considerable insight into the process of cell
      morphogenesis and the establishment of positional information in fission yeast.
      The highlights include a better understanding of the role of the microtubule
      cytoskeleton in the control of cell shape, as well as the identification of novel
      genes essential for the establishment of cell polarity and for the positioning of
      the site of cell division.

PMID- 10066549
TI  - Coordinate control of secondary metabolite production and asexual sporulation in
      Aspergillus nidulans.
AB  - Microbial secondary metabolite production is frequently associated with
      developmental processes such as sporulation, but there are few cases where this
      correlation is understood. Recent work with the filamentous fungus Aspergillus
      nidulans has provided new insights into the mechanisms coordinating production of
      the toxic secondary metabolite sterigmatocystin with asexual sporulation. These
      processes have been shown to be linked through a common need to inactivate a
      heterotrimeric G protein dependent signaling pathway that, when active, serves to
      stimulate growth while blocking both sporulation and sterigmatocystin
      biosynthesis.

PMID- 10066550
TI  - How and why myxobacteria talk to each other.
AB  - In response to starvation, myxobacteria build multicellular fruiting bodies that
      contain many thousands of cells and that have particular species-specific shapes.
      To coordinate fruiting body development, the myxobacterial cells signal to each
      other. The timing of and cellular responses to these signals help to give form to
      the fruiting body. Following identification of several signal molecules,
      important transcriptional regulators and other signals have recently been
      identified. Steps on signal transduction pathways have also been defined.

PMID- 10066551
TI  - Time at the end of the millennium: the Neurospora clock.
AB  - In the past two years we have entered the log phase for unraveling the molecular
      clockworks. Rapid progress in understanding the Neurospora clock has been
      complemented by a flood of information from diverse systems including
      cyanobacteria, insects and mice. There are broadly conserved features in
      transcription/translation based feedback loops. Conservation is also found at the
      sequence level, from fungi to mammals, in the PAS domains of the heterodimeric
      partners of the transcription factors that act as the positive components of the
      feedback cycle. Pivotal PAS proteins from Neurospora, the WCs, provide an
      evolutionary link connecting the clock in insects and mammals to the fungi and to
      light-harvesting proteins from bacteria.

PMID- 10066552
TI  - Developmental phenotypic plasticity: where internal programming meets the
      external environment.
AB  - Developmental plasticity has long been the focus of research in both evolutionary
      ecology and molecular genetics. Recently, the concept of ontogenetic contingency
      has been proposed to indicate the dependence of plastic responses on the timing
      and sequence of developmental events. Also, the idea of the developmental
      reaction norm has been put forward to indicate the complex interactions among
      development, phenotypic plasticity, and allometry of different structures.
      Finally, for the first time, studies ranging from the ecological to the molecular
      aspects of the same plastic response are available on insect and flowering plant
      model systems.

PMID- 10066553
TI  - The formation of leaves.
AB  - The past year has seen major advances in our understanding of the mechanisms
      through which leaf pattern is elaborated. It has been suggested that
      developmental subcompartments are delimited within the leaf and that homeobox
      genes are involved in specifying these domains in compound leaves. Importantly,
      peptide signaling has emerged as a novel component of leaf developmental
      pathways.

PMID- 10066554
TI  - Self-incompatibility and other pollen-pistil interactions.
AB  - Self-incompatibility allows plants to recognize and reject pollen from the same
      plant, thereby reducing inbreeding. Although in most cases self-incompatibility
      is controlled by a single genetic locus, recent results show that surprisingly
      complex signal transduction pathways and many players are involved in pollen
      recognition and rejection.

PMID- 10066555
TI  - Ovule and embryo development, apomixis and fertilization.
AB  - Genetic analyses, particularly in Arabidopsis, have led to the identification of
      mutants that define different steps of ovule ontogeny, pollen stigma interaction,
      pollen tube growth, and fertilization. Isolation of the genes defined by these
      mutations promises to lead to a molecular understanding of these processes.
      Mutants have also been obtained in which processes that are normally triggered by
      fertilization, such as endosperm formation and initiation of seed development,
      occur without fertilization. These mutants may illuminate apomixis, a process of
      seed development without fertilization extant in many plants.

PMID- 10066556
TI  - The evolution of plant development.
AB  - There has been much recent interest in the evolution of plant development and
      especially in trying to understand the developmental genetic basis of
      morphological evolution. Significant progress has been made in understanding the
      evolution of floral organization and the mechanisms that might underlie the
      evolution of compound leaves and inflorescence morphology. These advances are
      reinforcing the idea that phenotypic evolution can proceed via changes at few
      loci of large effect and that promoter evolution may be an important and frequent
      mechanism.

PMID- 10066557
TI  - Plant cell expansion: scaling the wall.
AB  - The regulation of plant cell size and shape is poorly understood at the molecular
      level. Recently, two loci required for normal cell expansion in Arabidopsis were
      cloned. They both encode enzymes involved in the construction of the cell wall.
      These studies are the first promising examples of the use of Arabidopsis
      molecular genetics for the study of wall synthesis and assembly during plant cell
      elongation.

PMID- 10066558
TI  - Control of flowering time.
AB  - The multiple promotive and repressive pathways controlling flowering have been
      further defined by analysis of genetic interactions and the activation of floral
      meristem identity genes. Cloning of additional genes in these pathways has
      uncovered some of the molecular processes that control the timing of the
      transition to reproductive development.

PMID- 10066559
TI  - Sex determination in plants.
AB  - Sex determination is an important developmental event in the life cycle of all
      sexually reproducing plants. Recent studies of sex determination in many plant
      species, from ferns to maize, have been fruitful in identifying the diversity of
      genetic and epigenetic factors that are involved in determining the sex of the
      flower or individual. In those species amenable to genetic analysis, significant
      progress has been made toward identifying mutations that affect sex expression.
      By studying the interactions among these genes, pictures of how sex-determining
      signals are perceived to activate or repress male- or female-specific genes are
      emerging.

PMID- 10066560
TI  - The evolutionary basis of leaf senescence: method to the madness?
AB  - Recent studies on the differential expression of genes associated with leaf
      senescence support the long-standing interpretation of plant senescence as an
      organized, genetically controlled process. Sequence identities of genes that are
      differentially expressed in senescing leaves indicate roles in the salvage of
      nutrients. By considering this salvage function as the selected trait and the
      degeneration and death of the tissue a pleiotropic consequence of nutrient
      redistribution, the process of leaf senescence can be reconciled with
      evolutionary theories on the origins of senescence in animals.

PMID- 10066561
TI  - Cell type specification and self renewal in the vegetative shoot apical meristem.
AB  - The vegetative shoot apical meristem of seed plants is the site of new leaf and
      stem formation. In the past few years genes that regulate fundamental aspects of
      shoot growth and development have been discovered. The recent study of these
      genes and their products through the use of appropriate mutants has opened new
      doors to understanding the molecular mechanisms of shoot apical meristem
      function.

PMID- 10066562
TI  - The blooming of grass flower development.
AB  - The past half decade has provided a wealth of information concerning the
      molecular and genetic control of floral organ and meristem identity in
      dicotyledonous plants. Comparatively little is understood about these processes
      in grass species in spite of the importance that these species play in human
      agriculture. The isolation of grass genes that are homologous to dicot floral
      homeotic genes in combination with recent advances in reverse genetic technology
      and improvements in cereal transformation opens the door for understanding
      molecular mechanisms of grass flower development. Such information will also
      focus attention on the evolutionary relationships between grass and dicot flowers
      and the degree to which the developmental pathways leading to reproductive organ
      development in divergent angiosperms have utilized conserved mechanisms.

PMID- 10066563
TI  - From floral induction to floral shape.
AB  - The initial emphasis in molecular-genetic studies of flower development was on
      homeotic genes that control organ identity, which is rather invariant between
      different species. Studies in flower development during the past three years have
      dealt with more diverse aspects of flower development, including floral induction
      and floral shape. Genes identified in the respective pathways might hold clues to
      the diversity of modern angiosperms.

PMID- 10066564
TI  - Root development: new meanings for root canals?
AB  - During Arabidopsis root development, a radial pattern of tissues is extended by
      the meristem. These tissues form continuous layers and recent data suggest that
      tissue continuity is instrumental for constraining the direction of signaling in
      a process termed channeling. In the ground tissue, fate-determining signals
      originate from contiguous cells of the same layer, possibly due to specific
      symplastic connections. Mutant analysis supports the hypothesis that vascular
      tissue continuity may facilitate and depend on the directional transport of a
      vascular fate-determining signal, possibly the phytohormone auxin.

PMID- 10066565
TI  - Growth and development: growing up green.

PMID- 10066567
TI  - Growth and development 

PMID- 10066568
TI  - To pair or not to pair: chromosome pairing and evolution.
AB  - Chromosome pairing in wild-type wheat closely resembles the process in both yeast
      and Drosophila. The recent characterisation of a mutant Ph1 wheat and the
      observation that chromosome pairing in the absence of Ph1 more closely resembles
      that of mammals and maize has shed light on the evolution of chromosome pairing
      in the cereals.

PMID- 10066569
TI  - Position effects and epigenetic silencing of plant transgenes.
AB  - Nuclear processes that silence plant transgenes are being revealed by analyses of
      natural triggers of epigenetic modifications, particularly cytosine methylation,
      and by comparisons of the genomic environments of differentially expressed
      transgene loci. It is increasingly apparent that plant genomes can sense and
      respond to the presence of foreign DNA in certain sequence contexts and at
      multiple dispersed sites. Determining the basis of this sensitivity and how
      nuclear defense systems are activated poses major challenges for the future.

PMID- 10066570
TI  - Controlling gene expression in transgenics.
AB  - The repertoire of cis-regulatory elements has increased to a level of
      sophistication that offers considerable spatial and temporal control over
      transgene expression. Recent advances made with transgenes have revealed that the
      control of their expression is also influenced by factors that range from
      transgene copy number and arrangement to nuclear architecture and chromosomal
      location. These factors must now be included with the standard considerations of
      transcriptional and translational enhancers of gene expression during transgene
      design.

PMID- 10066571
TI  - Genetic recombination in plants.
AB  - Meiotic recombination generates novel allelic arrays on chromosomes. Recent
      experiments have revealed an extraordinarily nonrandom distribution of
      recombination breakpoints along the lengths of plant chromosomes; for example,
      recombination breakpoints often resolve within genic sequences, and thereby
      generate novel alleles. The mechanism by which recombination breakpoints are
      determined is an area of active investigation. In addition, recent developments
      are providing recombination-based technologies for creating targeted alterations
      in the architecture of plant genomes.

PMID- 10066572
TI  - Advances in cereal gene transfer.
AB  - Over the past five years, transgenic strains of various major cereals have been
      produced, with transformation of rice and maize being most common. A majority of
      the cereal transformants obtained to date has been generated by the particle
      bombardment technique, but Agrobacterium-mediated transformation is rapidly
      becoming the method of choice. Rice, the plant in which transformation-related
      technology is most advanced, appears to be the model monocotyledon for basic and
      applied studies.

PMID- 10066573
TI  - Who's related to whom? Recent results from molecular systematic studies.
AB  - Similarities among model systems can lead to generalizations about plants, but
      understanding the differences requires systematic data. Molecular phylogenetic
      analyses produce results similar to traditional classifications in the grasses
      (Poaceae), and relationships among the cereal crops are quite clear. Chloroplast
      based phylogenies for the Solanaceae show that tomato is best considered as a
      species of Solanum, closely related to potatoes. Traditional classifications in
      the Brassicaceae are misleading with regard to true phylogenetic relationships
      and data are only now beginning to clarify the situation. Molecular data are also
      being used to revise our view of relationships among flowering plant families.
      Phylogenetic data are critical for interpreting hypotheses of the evolution of
      development.

PMID- 10066574
TI  - Large-scale sequencing of plant genomes.
AB  - The large number of ESTs generated for Arabidopsis and rice in recent years now
      act as an important complement to whole genome sequencing projects. The
      Arabidopsis Genome Initiative has begun a coordinated effort to sequence the
      entire genome and, as a result, increasing numbers of large sequence entries can
      be found in the public databases. In addition, the mitochondrial genome of
      Arabidopsis has been completely sequenced. Genome sequencing studies and the
      public sequence databases have begun to influence the direction of diverse areas
      of research from physiology to evolution.

PMID- 10066575
TI  - Plant cytogenetics at the dawn of the 21st century.
AB  - The years 1996-1997 saw advances in plant chromosome handling, structure,
      behaviour and manipulation. Improved protocols were developed for flow sorting,
      microdissection and microcloning. Fibre FISH was used to map a range of DNA
      sequences at a resolution of a few kilobases. Over 400 wheat deletion stocks were
      reported and healing of broken chromosomes by de novo addition of telomeric
      sequences was demonstrated. Centromeric DNA sequences were identified. The role
      of telomeric ends in pairing was demonstrated. Apparently unusually long
      chromosome arms can interfere with mitosis. Novel phenomena and potential of wide
      hybrids for genome analysis were noteworthy.

PMID- 10066576
TI  - Plant cell walls as targets for biotechnology.
AB  - Plants are the sources of major food, feed, and fiber products that are used
      globally. This past year has seen advances in our understanding of the enzymes
      that modify wall architecture, the cloning of the first cellulose synthase gene,
      and revisions to the lignin biosynthetic pathway. These discoveries have
      facilitated the development of new strategies to alter cell wall properties in
      transgenic plants.

PMID- 10066577
TI  - Manipulating flux through plant metabolic pathways.
AB  - The past two years have seen a marked increase in patent applications for novel
      methods of altering the level and spectrum of commercially important products in
      plants. Results from these studies have proven surprising, showing that in many
      cases those enzymes traditionally thought of as flux-controlling have no impact
      on product formation when they are directly altered by genetic manipulation. In
      many cases, successful induction of increased flux throughout an entire pathway
      has been achieved by targeting one of the terminal enzymes in the pathway.

PMID- 10066578
TI  - Plant centromeres: structure and control.
AB  - Recent work has led to a better understanding of the molecular components of
      plant centromeres. Conservation of at least some centromere protein constituents
      between plant and non-plant systems has been demonstrated. The identity and
      organization of plant centromeric DNA sequences are also beginning to yield to
      analysis. While there is little primary DNA sequence conservation among the
      characterized plant centromeres and their non-plant counterparts, some parallels
      in centromere genomic organisation can be seen across species. Finally, the
      emerging idea that centromere activity is controlled epigenetically finds support
      in an examination of the plant centromere literature.

PMID- 10066579
TI  - The structure and evolution of angiosperm nuclear genomes.
AB  - Despite several decades of investigation, the organization of angiosperm genomes
      remained largely unknown until very recently. Data describing the sequence
      composition of large segments of genomes, covering hundreds of kilobases of
      contiguous sequence, have only become available in the past two years. Recent
      results indicate commonalities in the characteristics of many plant genomes,
      including in the structure of chromosomal components like telomeres and
      centromeres, and in the order and content of genes. Major differences between
      angiosperms have been associated mainly with repetitive DNAs, both gene families
      and mobile elements. Intriguing new studies have begun to characterize the
      dynamic three-dimensional structures of chromosomes and chromatin, and the
      relationship between genome structure and co-ordinated gene function.

PMID- 10066580
TI  - Genome studies and molecular evolution. Commonalities, contrasts, continuity and
      change in plant genomes.

PMID- 10066581
TI  - Plant biotechnology.

PMID- 10066583
TI  - Genome studies and molecular genetics plant biotechnology 

PMID- 10066584
TI  - Molecular determinants of sink strength.
AB  - The manipulation of sink to source relations has been subject to extensive plant
      breeding programs aiming to improve harvest index and thereby crop yield. The
      introduction of molecular and biochemical tools has enabled scientists to
      investigate the underlying principles. This has opened up the fascinating
      possibility of identifying molecular determinants of sink strength and to further
      increase yield on a rational basis. In the past, transgenic plants with
      alterations in the activity of only one putative molecular determinant have been
      created and this strategy has not resulted in substantial and reliable increases
      in yield. Yet, careful molecular and biochemical investigations have provided
      valuable insight about carbon flux into different metabolic pathways at different
      stages of sink development and it has become apparent that this metabolic
      channelling needs to be exploited by using stage- and cell-specific promoters in
      attempts to increase sink strength.

PMID- 10066585
TI  - Sugar regulation of gene expression in plants.
AB  - The molecular details of sugar sensing and sugar-mediated signal transduction
      pathways are unclear but recent results suggest that hexokinase functions as an
      important plant sugar sensor in a way that is similar to that found in yeast. The
      use of mutants in Arabidopsis defective in specific signaling steps is of
      particular importance because these give access to the genes encoding components
      in the signaling pathways. In addition, the physiological analysis of such
      mutants may reveal the interaction of sugar-induced signaling pathways and those
      induced by other stimuli such as environmental or biotic stress.

PMID- 10066586
TI  - Nitrate transport: a key step in nitrate assimilation.
AB  - The nitrate assimilation pathway has been the matter of intensive research during
      the past decade. Many genes involved in low and high affinity nitrate uptake have
      been identified in fungi, algae and, more recently, in plants. The plant genes so
      far isolated are transcriptionally regulated; their inducibility by nitrate seems
      to be a common feature, shared by their homologs in fungi and algae. A number of
      questions remain to be elucidated regarding the physiological roles of these
      transporters and the regulation of their expression.

PMID- 10066587
TI  - Metabolite transporters in plastids.
AB  - Communication between plastids and the surrounding cytosol occurs via the
      plastidic envelope membrane. Recent findings show that the outer membrane is not
      as freely permeable to low molecular weight solutes as previously thought, but
      contains different channel-like proteins that act as selectivity filters. The
      inner envelope membrane contains a variety of metabolite transporters that
      mediate the exchange of metabolites between both compartments. Two new classes of
      phosphate antiporters were recently described that are different in structure and
      function from the known triose phosphate/phosphate translocator from
      chloroplasts. In addition, a cDNA coding for an ATP/ADP antiporter from plastids
      was isolated that shows similarities to a bacterial adenylate translocator.

PMID- 10066588
TI  - Plant sulfur metabolism--the reduction of sulfate to sulfite.
AB  - Until recently the pathway by which plants reduce activated sulfate to sulfite
      was unresolved. Recent findings on two enzymes termed 5'-adenylylsulfate (APS)
      sulfotransferase and APS reductase have provided new information on this topic.
      On the basis of their similarities it is now proposed that these proteins are the
      same enzyme. These discoveries confirm that the sulfate assimilation pathway in
      plants differs from that in other sulfate assimilating organisms.

PMID- 10066589
TI  - Novel insights in the control of tetrapyrrole metabolism of higher plants.
AB  - Tetrapyrrole biosynthesis has been the subject of numerous studies over several
      decades. In recent years scientific interest in plant tetrapyrrole biosynthesis
      has included both genetical and biochemical elucidation of almost every enzymatic
      step of the pathway and has focused to an increasing extent on the regulatory
      mechanism of the entire metabolic pathway, but in particular of key steps, such
      as synthesis of 5-aminolevulinate, magnesium chelatase or protochlorophyllide
      oxidoreductase.

PMID- 10066590
TI  - Phenylpropanoid biosynthesis and its regulation.
AB  - In the past year progress has been made in the manipulation of phenylpropanoid
      metabolism but several studies highlight gaps in our understanding of the
      biochemistry of these pathways. New components involved in transcriptional
      regulation of phenylpropanoid genes have been identified, including transcription
      factors and novel proteins that function upstream of DNA-binding proteins.

PMID- 10066591
TI  - Plant stress adaptations--making metabolism move.
AB  - Persistently sub-optimal environmental conditions constitute stress. Perception
      and signaling lead to protein expression changes, the activation of new
      biochemical pathways, and repression of others which are characteristic of the
      unstressed state. Protective metabolic adaptations alter physiological reactions
      of the whole plant. Paramount among the mechanisms are oxygen radical scavenging,
      maintenance of ion uptake and water balance, and reactions altering carbon and
      nitrogen allocation, such that reducing power is defused. Elements of the stress
      signaling pathways and proteins that lead to stress protection have recently
      become known.

PMID- 10066592
TI  - Protein phosphorylation and redox sensing in chloroplast thylakoids.
AB  - Transduction of light dependent signals to redox sensitive kinases in
      photosynthetic membranes modulates energy transfer to the photochemical reaction
      centres and regulates biogenesis, stability and turnover of thylakoid protein
      complexes. The occupancy of the quinol-oxidation site of the cytochrome bf
      complex by plastoquinol and the redox state of protein thiol groups act as
      elements of the signal transducing chains.

PMID- 10066593
TI  - Regulation of cytosolic enzymes in primary metabolism by reversible protein
      phosphorylation.
AB  - Recent discoveries have revealed that cytosolic enzymes of sugar, amino acid, and
      isoprenoid synthesis, sucrose breakdown and the plasma membrane H+-ATPase are
      regulated by reversible protein (serine/threonine) phosphorylation. In some
      cases, phosphorylation creates a phosphopeptide motif that is recognized by and
      binds to 14-3-3 proteins, and 14-3-3 binding changes the activity of the enzyme
      or ion pump. Intriguing new clues hint at how these cytosolic regulatory networks
      might link to signalling pathways triggered by hormones, nutrients, stresses,
      circadian rhythms, and other factors that regulate the growth and development of
      the whole plant.

PMID- 10066594
TI  - Glutathione-mediated detoxification systems in plants.
AB  - Recent work has highlighted the presence of diverse glutathione-dependent enzymes
      in plants with potential roles in the detoxification of both xenobiotic and
      endogenous compounds. In particular, studies on glutathione transferases are
      further characterising their role in xenobiotic metabolism, and also raising
      intriguing possible roles in endogenous metabolism. The solution of their three
      dimensional structures together with studies on their molecular diversity and
      substrate specificity is providing new insights into the function and
      classification of these enigmatic enzymes.

PMID- 10066597
TI  - Physiology and metabolism 

PMID- 10066595
TI  - Plant metabolism: where are all those pathways leading us?

PMID- 10066598
TI  - Transcriptional control of plant genes responsive to pathogens.
AB  - Transcriptional activation of genes is a vital part of the plants defence system
      against pathogens. Cis-acting elements within the promoters of many of these
      genes have recently been defined and investigators have started to isolate their
      cognate trans-acting factors. Some of these factors have counterparts in animals,
      whereas others are present only in plants, reflecting the fact that plants have
      developed a unique defence system.

PMID- 10066599
TI  - Development of the arbuscular mycorrhizal symbiosis.
AB  - The arbuscular mycorrhizal (AM) symbiosis formed between plant roots and fungi is
      one of the most widespread symbiotic associations found in plants, yet our
      understanding of events underlying its development are limited. The recent
      integration of biochemical, molecular and genetic approaches into analyses of the
      symbiosis is providing new insights into various aspects of its development. In
      the past year there have been advances in our understanding of the signals
      required for the formation of appressoria, the molecular changes in the root in
      response to colonisation, and components of the signal transduction pathways
      common to both the AM and Rhizobium symbioses.

PMID- 10066600
TI  - Fungal pathogenicity.
AB  - Successful penetration of living plant tissue by fungal pathogens is preceded by
      an exchange of signals between both organisms. Recent mutational approaches
      revealed the importance of cAMP-dependent signalling pathways for fungal
      development and virulence on their hosts.

PMID- 10066601
TI  - Structure and function of proteins controlling strain-specific pathogen
      resistance in plants.
AB  - Recently recognised structural and amino acid sequence similarities between plant
      disease resistance (R) proteins and animal proteins such as Apaf-1 and CED-4 are
      providing conceptual models for resistance protein function. Data from extensive
      DNA sequencing of resistance gene families are indicating that the leucine-rich
      repeat motif is an important determinant of gene-for-gene specificity and that
      intergenic DNA sequence exchange is a major contributor to R gene diversity.

PMID- 10066602
TI  - Genetic dissection of R gene signal transduction pathways.
AB  - Mutant screens have identified several genes in tomato, barley and Arabidopsis
      that are required for the function of specific plant disease resistance (R)
      genes. Two of these genes, NDR1 and EDS1, have recently been cloned from
      Arabidopsis. Most Arabidopsis R genes require NDR1 or EDS1, but not both. In a
      complementary approach, yeast two-hybrid screens have identified several proteins
      in tomato that interact with the Pto R gene protein, including a kinase and three
      putative transcription factors. The present data indicate that R gene proteins
      directly activate multiple signal transduction pathways, and that common defense
      responses can be activated via independent pathways.

PMID- 10066603
TI  - Determinants of pathogenicity and avirulence in plant pathogenic bacteria.
AB  - Many plant pathogenic bacteria possess a conserved protein secretion system that
      is thought to transfer Avr (avirulence) proteins, with potential activities in
      both parasitism and defense elicitation, into plant cells. avr genes may be
      acquired horizontally by these bacteria, and avr gene compositions are highly
      variable. In the past year, heterologous expression experiments have revealed
      that the products of avr genes can be interchanged among different genera of
      bacteria with retention of secretion, pathogenicity, and avirulence activities,
      suggesting mechanisms for rapid coevolution of these parasites with changing
      plant hosts.

PMID- 10066604
TI  - Resistance gene evolution.
AB  - Plant resistance genes are highly polymorphic and have diverse recognition
      specificities. These genes often occur as members of clustered gene families that
      have evolved through duplication and diversification. Regions of nucleotides
      conserved between family members and flanking sequences facilitate equal or
      unequal recombination events. Transposition contributes to allelic diversity.
      Resistance gene clusters appear to evolve more rapidly than other regions of the
      genome, and domains responsible for recognitional specificity, such as the
      leucine-rich repeat domain, are subject to adaptive selection.

PMID- 10066605
TI  - Genes and signal molecules involved in the rhizobia-leguminoseae symbiosis.
AB  - The symbiosis between Rhizobium bacteria and their host plants is dependent on
      the specific recognition of signal molecules produced by each partner. Many
      players in the signal exchange have been identified. Among them are signal
      molecules such as flavonoids, LCOs, auxin, cytokinin, ethylene and uridine and
      genes such as Enod40, Enod2 and Enod12. Their interconnection, however, is only
      starting to be understood. The most recent insights into their interconnection
      include: advances in the use of transgenic leguminous plants containing reporter
      gene constructs for studying the effect of the signal molecules; novel methods
      for delivery of signal molecules using ballistic microtargeting; and the
      discovery of the role of chitin oligosaccharides in animal embryogenesis.

PMID- 10066606
TI  - Viral invasion and host defense: strategies and counter-strategies.
AB  - The outcome of infection of plants by viruses is determined by the net effects of
      compatibility functions and defense responses. Recent advances reveal that
      viruses have the capacity to modulate host compatibility and defense functions by
      a variety of mechanisms.

PMID- 10066607
TI  - SA, JA, ethylene, and disease resistance in plants.
AB  - Exciting advances have been made during the past year: isolating mutants
      affecting plant disease resistance, cloning genes involved in the regulation of
      various defense responses, and characterizing novel defense signaling pathways.
      Recent studies have demonstrated that jasmonic acid and ethylene are important
      for the induction of nonspecific disease resistance through signaling pathways
      that are distinct from the classical systemic acquired resistance response
      pathway regulated by salicylic acid.

PMID- 10066608
TI  - The soybean cyst nematode, Heterodera glycines: a genetic model system for the
      study of plant-parasitic nematodes.
AB  - Despite advances in understanding plant responses to nematode infection, little
      information exists regarding parasitic mechanisms. Recently, it has become
      possible to perform genetic analysis of soybean cyst nematode. Integration of
      classic and reverse genetics and genomic approaches for the parasite, with host
      genetics and genomics will expand our knowledge of nematode parasitism.

PMID- 10066609
TI  - Resistance response physiology and signal transduction.
AB  - Plants defend themselves against pathogen attack by activating a multicomponent
      defense response. The activation of this response requires recognition of the
      pathogen and initiation of signal transduction processes that finally result in a
      spatially and temporally regulated expression of individual defense reactions.
      Several components involved in signaling resistance reactions have recently been
      identified and characterized.

PMID- 10066612
TI  - Plant biology 

PMID- 10066610
TI  - Transgenic approaches to microbial disease resistance in crop plants.
AB  - Recent progress in the genetic dissection of plant disease resistance signaling
      pathways has opened a number of new avenues towards engineering pathogen
      resistance in crops. Genes controlling race-specific and broad-spectrum
      resistance responses have been cloned, and novel induced resistance pathways have
      been identified in model and crop systems. Advances continue to be made in
      identification of antifungal proteins with effects inhibitory to either pathogen
      development or accumulation of associated mycotoxins.

PMID- 10066613
TI  - Plant-microbe interactions 

PMID- 10066614
TI  - Ca2+ signalling in plant cells: the big network!
AB  - Significant advances in Ca2+ and calmodulin signalling in whole plants and
      individual cells have been recently reported. Particular relevant contributions
      have been made to the study of the modification of gene expression by osmotic,
      light and gravity signals and the growth of root hairs and pollen tubes.

PMID- 10066615
TI  - Plants embrace a stepchild: the discovery of peptide growth regulators.
AB  - Over the past decade, peptides have been added to the collection of signalling
      molecules in plants. As the impact of peptide hormones in non-plants is enormous,
      a comparison of plant and non-plant peptide signal molecules at this stage
      deserves our attention-not only to reveal common and unique features, but also to
      point to new avenues of future research on plant hormones.

PMID- 10066616
TI  - Jasmonate and salicylate as global signals for defense gene expression.
AB  - Remarkably, only a few low molecular mass signals, including jasmonic acid,
      ethylene and salicylic acid, upregulate the expression of scores of defense
      related genes. Using these regulators, the plant fine-tunes its defense gene
      expression against aggressors which, in some cases, may be able to disrupt or
      amplify plant defense signal pathways to their own ends.

PMID- 10066617
TI  - Recent advances in brassinosteroid molecular genetics.
AB  - The importance of brassinosteroids (BRs, a specific class of ecdysone-like plant
      steroids) as essential endogenous regulators of growth and development is
      demonstrated through a growing number of well characterised Arabidopsis, pea, and
      tomato mutants deficient in BR biosynthesis or BR response. Thus, a rapid
      advancement in understanding the molecular genetics of BR biosynthesis and mode
      of action can be witnessed, which will be further enhanced through the
      availability of a set of extremely valuable molecular tools for the analysis of
      the biological function of BRs.

PMID- 10066618
TI  - Gibberellin signaling.
AB  - Recent findings provide insights into the gibberellin signaling system in plants.
      Genes for gibberellin biosynthetic enzymes have been cloned, and an emerging
      theme is that gibberellin biosynthesis is negatively regulated by gibberellin
      responses. Mutants defective in gibberellin signaling have been analyzed, and an
      important finding is that gibberellin represses growth inhibition. The list of
      intracellular gibberellin signal-transduction elements has been expanded to
      include G-proteins and protein kinases.

PMID- 10066619
TI  - Challenges in understanding RLK function.
AB  - Plants use receptor-like kinases (RLKs) to transduce extracellular signals into
      the cell. Recent advancements in RLK research include the cloning of the
      BRASSINOSTEROID INSENSITIVE 1 and CLAVATA 1 genes, revealing RLK roles in
      development. Our understanding of RLK function has also been broadened by
      transgenic approaches in the study of the RLKs pollen receptor kinase 1, and wall
      associated kinase 1. These results extend the observations that RLKs function in
      developmental processes and plant defense responses. Additionally, expression
      based studies suggest roles for other newly reported RLKs in development and
      light responses. Taken together, the studies confirm the importance of RLKs in
      diverse plant processes, yet major challenges remain. These include identifying
      ligands that activate RLKs and characterizing downstream pathways. These
      challenges can be conquered by coordinated efforts from investigators using
      molecular, genetic, and biochemical approaches.

PMID- 10066620
TI  - Cytokinin signaling.
AB  - Although cytokinin plays a central role in plant development, our knowledge of
      the biosynthesis, distribution, perception and signal transduction of cytokinin
      is limited. Recent molecular-genetic studies have, however, implicated
      involvement of a two-component system in cytokinin signal transduction.
      Furthermore, new mutants with altered cytokinin responses and genes involved in
      cytokinin signaling have been identified.

PMID- 10066621
TI  - Recent advances in the regulation of plant calcium channels: evidence for
      regulation by G-proteins, the cytoskeleton and second messengers.
AB  - Important aspects of the regulatory properties of plant calcium channels have
      been discovered during the past few years. These include the control of plasma
      membrane-bound channels by regulatory proteins and the characterization of a
      plethora of intracellular calcium release channels. Deciphering the mechanisms of
      regulation of different Ca2+ channels and the probable co-operation of their
      activities in response to various stimuli is leading to a better understanding of
      Ca2+-signalling processes in higher plants.

PMID- 10066622
TI  - The alphabet soup of plant intracellular signalling: enter cyclic nucleotides.
AB  - Recent work reveals a role for cyclic nucleotides as secondary signalling
      molecules in a variety of signal transduction pathways in plants. Evidence is
      accumulating that cGMP is involved in signalling during photomorphogenesis and
      that cADP-ribose triggers the release of sequestered Ca2+ during the response of
      plant cells to abscisic acid. Though more tentative, cAMP has been proposed as
      playing an important role in ion channel activity and cell cycle progression.
      Taken together, a picture emerges of differing signalling pathways, possibility
      interacting with each other, acting on an array of developmental processes.

PMID- 10066623
TI  - Molecular mechanisms of auxin action.
AB  - The plant growth hormone auxin has an important role in a variety of plant growth
      and developmental processes. Identification of transcription factors, some with
      defined genetic function, has shed new light on the mechanisms of auxin regulated
      gene expression. In addition, the molecular characterization of genes required
      for auxin response indicates that regulated protein degradation by the ubiquitin
      proteosome pathway has an important function in auxin action.

PMID- 10066624
TI  - Ethylene gas: perception, signaling and response.
AB  - During the last decade a genetic approach based on the Arabidopsis 'triple
      response' to the hormone ethylene has allowed the identification of numerous
      components of the signal transduction pathway. Cloning of the genes and
      biochemical analysis of the proteins that they encode are uncovering the
      molecular mechanisms that allow a plant cell to perceive and respond to this
      gaseous regulator of plant growth/stress responses.

PMID- 10066625
TI  - ABA signal transduction.
AB  - Recent advances in the study of abscisic acid signal transduction include the
      identification of cyclic ADP-ribose as a central mediator of abscisic acid
      responses. The characterisation of type 2C protein phosphatases, ABI1 and ABI2,
      implicates negative control and redundant action on the signal pathway of this
      hormone. In addition, abscisic acid-mediated inhibition of gibberellin-stimulated
      responses seems to depend on the activation of a phospholipase D during induction
      of alpha-amylase in barley aleurone cells as well as on a putative
      acetyltransferase involved in elongation growth.

PMID- 10066626
TI  - Cell walls: structures and signals.
AB  - Cell walls harbor proteins and polysaccharides able to condition the development
      of a plant. In the past year, genes and enzymes modulating the composition and
      physical properties of walls have been characterized, and wall composition has
      been linked to the way a cell interacts with another cell, and to the way in
      which it differentiates. The sum of the signaling and physical activities of a
      cell wall may explain much about the control of development.

PMID- 10066627
TI  - Meiosis: vive la difference!
AB  - The application of molecular and modern cell biological techniques is beginning
      to show that the classical picture of the meiotic process is an
      oversimplification. The comparison of different species and analysis of mutants
      have recently demonstrated that many of the features previously thought to be an
      integral part of meiosis can be altered in their timing or even entirely
      dispensed with. In plants, differences in the meiotic pathway have been observed,
      by using methods for 3-D optical imaging, between the polyploids maize and wheat.
      The fact that two such closely related species differ may be the result of
      different mechanisms for dealing with polyploidy or may be species differences,
      but shows that a detailed understanding of the process in the particular species
      of interest is necessary.

PMID- 10066628
TI  - Signaling tip growth in plants.
AB  - Tip growth is an extreme form of polar growth modulated by both intrinsic and
      extrinsic spatial cues. Pollen tubes and root hairs have been used as model
      systems to investigate tip growth signaling in higher plants. Recent studies have
      focused on tip-localized Ca2+ gradients and Rho GTPases in pollen tubes and a
      series of mutants affecting root hair tip growth. These molecular and genetic
      markers will serve as stepping stones towards uncovering tip growth pathways in
      plants.

PMID- 10066629
TI  - Cellular differentiation in the shoot epidermis.
AB  - The recent advances in defining genes involved in shoot epidermal cell
      differentiation are impressive, especially the characterisation of genes involved
      in cellular patterning. The additional influences of environment and hormones on
      cellular patterning have recently been emphasised, and important connections have
      been made to changes in vegetative and reproductive growth phases. Despite these
      advances the cellular basis for differentiation remains less well defined, but
      now genetic and cell biological analysis from yeast may provide important models
      on which to develop further understanding.

PMID- 10066630
TI  - The retinoblastoma pathway in plant cell cycle and development.
AB  - The activity of cyclin-dependent kinases (CDKs) on specific targets mediates the
      temporal regulation of plant cell cycle transitions. The sequential activity of
      CDKs and the spatial regulation of cell proliferation during plant development,
      however, are still poorly understood. Understanding these aspects depends on the
      identification of the downstream targets and upstream modulators of CDKs and
      their regulation in response to mitogenic and/or differentiation signals. Current
      efforts to elucidate the answers to these questions are very promising; in
      particular, recent works reveal the essential role that the retinoblastoma
      pathway plays in controlling cell cycle progression and, presumably, some
      developmental events.

PMID- 10066631
TI  - Protein transport within the plant cell endomembrane system: an update.
AB  - The secretory pathway plays a central role in plant development and
      morphogenesis. Storage protein deposition, plant cell division and the expansion
      of the plasma membrane and extracellular matrix all require the synthesis and
      trafficking of membranes, proteins and polysaccharides through this network of
      organelles. Increasing evidence demonstrates that the plant secretory pathway is
      more complex than previously appreciated and that its formation and maintenance
      are guided/regulated by many different mechanisms.

PMID- 10066632
TI  - Genetics of plant cell shape.
AB  - Plant cells have a variety of shapes crucial for their functions, yet the
      mechanisms that generate these shapes are poorly understood. Genetic dissection
      of the trichome (plant hair) branching pathway in Arabidopsis, has uncovered
      mechanisms and identified genes that control plant cell morphogenesis. The recent
      identification of one of these genes, ZWICHEL (ZWI), as a novel member of the
      kinesin superfamily of microtubule motors provides a starting point for the
      analysis of the plant cytoskeleton's role in a specific morphogenetic event.

PMID- 10066633
TI  - Regulated nuclear targeting.
AB  - Extracellular signals are transduced to the nucleus through respective signal
      transduction pathways. Evidence in animals and yeast indicates the importance of
      regulated nuclear targeting in these processes. Although little is known about
      plants in this regard, some plant signaling factors have recently been shown to
      translocate to the nucleus upon receipt of a signal.

PMID- 10066634
TI  - Cytokinesis in flowering plants: cellular process and developmental integration.
AB  - In phragmoplast-assisted cytokinesis of somatic cells, vesicle fusion generates a
      cell plate that matures into a new cell wall and its flanking plasma membranes.
      Insight into this dynamic process has been gained in the past few years and
      additional molecular components of the basic machinery of cytokinesis have been
      identified. Specialized modes of cytokinesis occur in meiosis and gametophyte
      development, and recent studies indicate that they are genetically distinct from
      somatic cytokinesis.

PMID- 10066635
TI  - Plastid division: evidence for a prokaryotically derived mechanism.
AB  - Plastid division is a critical process in plant cell biology but it is poorly
      understood. Recent studies combining mutant analysis, gene cloning, and
      exploitation of genomic resources have revealed that the molecular machinery
      associated with plastid division is derived evolutionarily from the bacterial
      cell division apparatus. Comparison of the two processes provides a basis for
      identifying new components of the plastid division mechanism, but also serves to
      highlight the differences, not least of which is the nuclear control of the
      plastid division process.

PMID- 10066636
TI  - Auxin signaling in Arabidopsis flower development?

PMID- 10066637
TI  - Dead cells do tell tales.
AB  - The most recent major advances in the study of programmed cell death (PCD) in
      plants include the observation that peptide inhibitors of caspases inhibit the
      hypersensitive response. Nitric oxide has been shown to be required for the
      induction of disease related PCD. Mutant analysis has led to the cloning of the
      first genes involved in PCD related disease resistance, LSD1 and MLO.

PMID- 10066638
TI  - Endoreduplication and development: rule without dividing?
AB  - Endoreduplication, a strategy to amplify nuclear DNA without cell division, is
      very common but poorly understood in plants. Recent findings in Drosophila
      provide a first picture of the molecular mechanism, which appears to be conserved
      between plants and animals. In Arabidopsis, the study of trichomes, leaf
      epidermis and hypocotyl cells sheds new light on the developmental regulation of
      this process, and its relation to cell expansion.

PMID- 10066639
TI  - Oxidant-induced lung injury in anticancer therapy.
AB  - Lung injury is one of the most frequent side effects in anticancer therapy.
      Especially simultaneous application of high doses of ionising radiation and
      radiosensitising cytotoxic drugs is considered to cause deleterious pneumonitis
      and pulmonary fibrosis. Growing evidence indicates that reactive oxygen species
      (ROS) play a key role in the development of these disorders. They are capable of
      causing cell component alterations and changing cellular protein expression.
      Observing these disease mechanisms reveals an impressive self-amplifying cascade
      of secondary ROS generation. Through intricate interactions between cells,
      cytokines and growth factors, fibroblasts are activated and thus pulmonary matrix
      content is massively increased. - As clinical appearance is uniform and
      unspecific, an early, reliable diagnosis of therapy-associated lung damage is not
      possible so far. However, improving this situation could enable us to take
      advantage of new multimodal therapeutic facilities. This review discusses
      mechanisms of ROS generation during radio-chemotherapy in the lung, antioxidant
      defense strategies and responses to oxidants, thereby assessing current
      diagnostic tools.

PMID- 10066640
TI  - Virological efficacy and plasma drug concentrations of nelfinavir plus saquinavir
      as salvage therapy in HIV-infected patients refractory to standard triple
      therapy.
AB  - Therapeutic options are limited for patients refractory to triple therapy with
      two reverse transcriptase inhibitors and one protease inhibitor. Preliminary
      results showing favorable effects of protease inhibitor combination therapy with
      nelfinavir and saquinavir due to inhibition of metabolism by cytochrome P450
      (CYP450) prompted us to study this combination. - Thirteen patients with
      incomplete suppression of plasma HIV-RNA were enrolled and treatment was started
      with nelfinavir 750 mg tid and saquinavir 400 mg bid. Saquinavir-dosage was
      escalated in weekly intervals to 400 mg tid and 600 mg tid, respectively. All
      doses were given with food, and plasma levels of saquinavir and nelfinavir were
      assessed 4 hours post-dosing after 1, 2, 3, 4 and 8 weeks. Treatment was
      considered virologically efficacious if HIV-viral load was reduced by at least
      0.5 log10 from baseline. - Double protease inhibitor-treatment with nelfinavir
      and saquinavir was virologically efficacious in 5/13 (39%) patients after 4 weeks
      but only in 4/13 (31%) patients after 8 and 1/13 (8%) after 16 and 24 weeks,
      respectively. No statistical difference in plasma concentrations was observed
      when saquinavir was administered in increasing doses of 400 mg bid, 400 mg tid or
      600 mg tid in combination with nelfinavir. 5/13 (39%) patients developed diarrhea
      (>4/d), no other serious side-effects were observed. By eight weeks, the mean CD4
      count for all patients was significantly higher when compared to baseline. - In
      patients refractory to standard triple therapy the combination of nelfinavir and
      saquinavir showed significant elevation of CD4-count, but only short term
      virological efficacy in a minority of patients. Plasma concentrations of
      saquinavir could not be increased by weekly dose escalation of the drug from 400
      mg bid to 600 mg tid. Saquinavir drug concentrations of 600 mg saquinavir tid and
      nelfinavir showed rather non-significant lower values when compared to historical
      controls treated with a double-dose 1200 mg saquinavir tid regimen alone. We
      conclude that in these patients the combination of nelfinavir plus saquinavir has
      no advantage in terms of increasing bioavailibility of saquinavir or virological
      efficacy. During short observation time a beneficial effect on CD4-count was
      observed.

PMID- 10066641
TI  - Additional NO2 exposure induces a decrease in cytokine specific mRNA expression
      and cytokine release of particle and fibre exposed human alveolar macrophages.
AB  - Soot particles, asbestos fibres and irritant gas are common air pollutants which
      are able to induce lung and airway pulmonary injury. The aim of this study was to
      investigate the effect of a simultaneous NO2 and particle or fibre exposure on
      the proinflammatory specific mRNA expression and protein secretion of human
      alveolar macrophages (AM) in comparison to only particle or fibre exposed AM. AM
      were simultaneously exposed to FR 101, P 90, TiO2 or Chrysotile B at a
      concentration of 100 microg/10(6) cells and to NO2 at a concentration of 1.0 ppm
      for 30 min. Particle or fibre exposure of the AM was continued in humidified air
      at 5% CO2 and 37 degrees C for an additional hour (harvesting of total RNA) or
      additional 7 hrs (harvesting of culture supernatant). The mRNA expression of the
      proinflammatory cytokines IL-1beta, IL-6, IL-8 and TNF-alpha of NO2
      particle/fibre co-exposed AM and only particle or fibre exposed AM was detected
      using specific RT-PCR. IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific protein
      secretion was measured by ELISA. Cytotoxicity was detected by
      lactatedehydrogenase quantification in the culture supernatant. We observed an
      increased IL-1beta-, IL-6-, IL-8- and TNF-alpha-specific mRNA expression of
      particle or fibre exposed AM, which was decreased after an additional NO2
      exposure. Also the particle or fibre exposure induced significant increase in IL
      1beta-, IL-6-, IL-8 and TNF-alpha-release of AM which was decreased after an
      additional NO2 exposure (p <0.031). The relative cytotoxicity of the NO2
      particle/fibre co-exposure was higher than the particle or fibre induced
      cytotoxicity, but mostly <10%. Therefore it is concluded that particle or fibre
      exposure may result in an increase in proinflammatory cytokine release by AM,
      which may be decreased by toxic NO2 due to the oxidative potential (e.g.
      lipidperoxydation) of this irritant gas. Particle, asbestos fibre and irritant
      gas exposure may induce airway and pulmonary injury by the activation of AM and
      consecutive proinflammatory cytokine release.

PMID- 10066642
TI  - Lymphocyte transformation test for the evaluation of adverse effects of
      antituberculous drugs.
AB  - The usefulness of the lymphocyte transformation test (LTT) for the analysis of
      adverse reactions to antituberculous drugs was evaluated. - The LTT was performed
      with isoniazid and rifampicin in 15 tuberculosis and 2 MOTT (Mycobacteria other
      than tuberculosis)-infection patients who suffered drug reactions, in 23 patients
      without any adverse reactions, in 7 controls previously exposed to
      antituberculous drugs, and in 14 controls who had never been exposed. 4/15 of the
      hepatotoxic reactions only showed a positive LTT with rifampicin, 3/15 only with
      isoniazid, and in 8/15 the LTT was negative. In an anaphylactoid shock reaction
      the LTT was extremely exaggerated for both rifampicin and isoniazid. In patients
      without any side effects only one slightly increased LTT due to isoniazid was
      observed. Two healthy controls with previous contact to these drugs showed a
      positive LTT for isoniazid, one of those with both rifampicin and isoniazid. The
      LTT was negative in all control persons without any former contact to
      antituberculous medications. In most cases hepatotoxicity seems to be a pure
      toxic reaction without the participation of cellular immune mechanisms. LTT can
      be useful for identifying the drug responsible for immunological side effects.

PMID- 10066643
TI  - Fear of dental treatment and its possible effects on oral health.
AB  - Working with 59 ambulant patients (average age 42 +/- 16 years), male and female,
      at the Dental Clinic of the University of Mainz, questions concerning fear of
      treatment were raised, and the answers compared with clinical findings on the
      status of oral health and with habits of oral hygiene. Pulse and blood pressure
      were also measured before and after treatment. 65% of the patients reported some
      level of fear of dental treatment. Younger patients had significantly more fear
      of treatment than older patients (p <0.05, Fisher-test). Patients reported the
      noise and vibration of the drill (56%), the sight of the injection needle (47%)
      and sitting at the treatment chair (42%) as especially fear provoking. As
      subjective elements of their fear, the patients reported muscle tension (64%),
      higher heart-beat (59%), accelerated breathing (37%), sweating (32%), and stomach
      cramps (28%). Among fearful patients, greater changes in pulse rate (>10
      beats/min) and changes in blood pressure were measured. Oral health correlated
      with levels of fear only for younger patients. Although the frequency of caries
      (DMF/T) and the degree of treatment need (CPITN) showed a significant correlation
      (p >0.005) with subjective fear of treatment among patients under 35 years of
      age, the correlation weakens with increasing age of the patients studied. The
      present findings strongly suggest the need for more prophylactic measures, and
      dental education, in kindergartens and elementary schools. By such means, a
      considerable improvement in levels of oral hygiene might be achieved, together
      with lower levels of fear of dental treatment.

PMID- 10066644
TI  - Investigations of bone turnover in renal osteopathy.
AB  - The renal bone disease which develops in chronic renal failure (CRF) is not an
      uniform disorder. Histomorphometry is accepted to be the best method for
      characterising the state of disease. The purpose of this study was to evaluate
      the suitability of pyridinium crosslinks in serum and urine as indicators of bone
      degradation processes. Patients with CRF had significantly higher Pyridinoline
      (Pyd) and Deoxypyridinoline (Dpyd) levels in serum and urine compared to normal
      controls except the urinary excretion in the subgroup of glomerulonephritis. A
      correlation was found between the serum levels of crosslinks and those of both
      creatinine and parathormone. The Pyd and Dpyd serum levels in patients under
      dialysis treatment were significantly higher than those of normal controls. With
      regard to bone turnover urinary crosslink measurements are of minor importance in
      CRF. In contrast, serum measurements could be helpful in revealing bone
      resorption both in patients with CRF and those under dialysis treatment.

PMID- 10066645
TI  - Immunological features of Pneumocystis carinii infection in humans.

PMID- 10066646
TI  - Anti-endothelial cell antibodies in systemic sclerosis.

PMID- 10066647
TI  - Immunodeficiency due to a unique protracted developmental delay in the B-cell
      lineage.
AB  - A unique immune deficiency in a 24-month-old male characterized by a transient
      but protracted developmental delay in the B-cell lineage is reported. Significant
      deficiencies in the number of B cells in the blood, the concentrations of
      immunoglobulins in the serum, and the titers of antibodies to T-dependent and T
      independent antigens resolved spontaneously by the age of 39 months in a sequence
      that duplicated the normal development of the B-cell lineage: blood B cells
      followed by immunoglobulin M (IgM), IgG, IgA, and specific IgG antibodies to T
      independent antigens (pneumococcal polysaccharides). Because of the sequence of
      recovery, the disorder could have been confused with other defects in humoral
      immunity, depending on when in the course of disease immunologic studies were
      conducted. Investigations of X-chromosome polymorphisms suggested that the
      disorder was not X linked in that the mother appeared to have identical X
      chromosomes. An autosomal recessive disorder involving a gene that controls B
      cell development and maturation seems more likely. In summary, this case appears
      to be a novel protracted delay in the development of the B-cell lineage, possibly
      due to an autosomal recessive genetic defect.

PMID- 10066648
TI  - Development of a Western blot assay for detection of bovine immunodeficiency-like
      virus using capsid and transmembrane envelope proteins expressed from recombinant
      baculovirus.
AB  - A 120-amino-acid polypeptide selected from the transmembrane protein region (tTM)
      and the major capsid protein p26 of bovine immunodeficiency-like virus (BIV) were
      expressed as fusion proteins from recombinant baculoviruses. The antigenic
      reactivity of both recombinant fusion proteins was confirmed by Western blot with
      bovine and rabbit antisera to BIV. BIV-negative bovine sera and animal sera
      positive for bovine syncytial virus and bovine leukemia virus failed to recognize
      the recombinant fusion proteins, thereby showing the specificity of the BIV
      Western blot. One hundred and five bovine serum samples were tested for the
      presence of anti-BIV antibodies by the recombinant protein-based Western blot and
      a reference Western blot assay using cell culture-derived virions as test
      antigens. There was a 100% concordance when the p26 fusion protein was used in
      the Western blot. However, the Western blot using the tTM fusion protein as its
      test antigen identified four BIV-positive bovine sera which had tested negative
      in both the p26 recombinant-protein-based and the reference Western blot assays.
      This resulted in the lower concordance of 96.2% between the tTM-protein-based and
      reference Western blot assays. The results of this study showed that the
      recombinant p26 and tTM proteins can be used as test antigens for the
      serodetection of BIV-infection in animals.

PMID- 10066649
TI  - Predominant immunoglobulin A response to phase II antigen of Coxiella burnetii in
      acute Q fever.
AB  - Diagnosis of acute Q fever is usually confirmed by serology, on the basis of anti
      phase II antigen immunoglobulin M (IgM) titers of >/=1:50 and IgG titers of
      >/=1:200. Phase I antibodies, especially IgG and IgA, are predominant in chronic
      forms of the disease. However, between January 1982 and June 1998, we observed
      anti-phase II antigen IgA titers of >/=1:200 as the sole or main antibody
      response in 10 of 1,034 (0.96%) patients with acute Q fever for whom information
      was available. In order to determine whether specific epidemiological or clinical
      factors were associated with these serological profiles, we conducted a
      retrospective case-control study that included completion of a standardized
      questionnaire, which was given to 40 matched controls who also suffered from
      acute Q fever. The mean age of patients with elevated phase II IgA titers was
      significantly higher than that usually observed for patients with acute Q fever
      (P = 0.026); the patients were also more likely than controls to live in rural
      areas (P = 0.026) and to have increased levels of transaminase in blood (P =
      0.03). Elevated IgA titers are usually associated with chronic Q fever and are
      directed mainly at phase I antigens. Although the significance of our findings is
      unexplained, we herein emphasize the fact that IgA antibodies are not specific
      for chronic forms of Q fever and that they may occasionally be observed in
      patients with acute disease. Moreover, as such antibody profiles may not be
      determined by most laboratories, which test only for total antibody titers to
      phase I and II antigens, the three isotype-specific Ig titers should be
      determined as the first step in diagnosing Q fever.

PMID- 10066650
TI  - Timing of development of measles-specific immunoglobulin M and G after primary
      measles vaccination.
AB  - A standard method for diagnosing measles is to detect measles-specific
      immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive
      IgM result from a person with suspected measles can be difficult if the person
      has recently received a measles vaccine. We have previously demonstrated that
      measles-specific IgM may persist for at least 8 weeks after primary vaccination,
      but it is unknown how quickly IgM appears. This study determined the timing of
      the rise of measles-specific IgM and IgG after primary measles vaccination with
      Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia
      presenting for routine measles vaccination were enrolled. Sera were collected
      before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles
      specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect
      IgG EIA. A total of 209 of the 224 children who returned for the second visit had
      prevaccination sera that were both IgM and IgG negative. The postvaccination IgM
      positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at
      3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at
      1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an
      IgM-positive result obtained by this antibody capture EIA is difficult to
      interpret if serum is collected between 8 days and 8 weeks after vaccination; in
      this situation, the diagnosis of measles should be based on an epidemiologic
      linkage to a confirmed case or on the detection of wild-type measles virus.

PMID- 10066651
TI  - Rotavirus G-type restriction, persistence, and herd type specificity in Swedish
      cattle herds.
AB  - G-typing of rotavirus strains enables the study of molecular epidemiology and
      gathering of information to promote disease prevention and control. Rotavirus
      strains in fecal specimens from neonatal calves in Swedish cattle herds were
      therefore characterized by using G1 to -4-, G6-, G8-, and G10-specific primers in
      reverse transcription (RT)-PCR. Fecal samples were collected from one dairy herd
      (herd A) for 4 consecutive years and from 41 beef and dairy herds (herd B)
      experiencing calf diarrhea outbreaks. Altogether, 1, 700 samples were analyzed by
      group A rotavirus enzyme-linked immunosorbent assay, and 98 rotavirus-positive
      specimens were selected for G-typing by RT-PCR. The effect of herd type, time,
      geographic region, and clinical symptoms on the G-type distribution was
      evaluated. Altogether (herds A and B), G10 was found in 59 (60. 2%) fecal
      specimens, G6 was found in 30 (30.6%) specimens, G3 was found in 1 (1.0%)
      specimen, and G8 was found in 1 (1.0%) specimen. Seven (7.1%) fecal specimens
      were not typeable. Herd type specificity in the G-type distribution was
      demonstrated in the herds in herd B. In the 6 beef suckler herds, only G6 was
      detected, while rotavirus strains from the 35 dairy herds were predominantly
      (54%) G10. The G-type distribution was restricted in herds A and B. Twenty-nine
      of 30 strains from herd A were characterized as G10. In the vast majority of
      herds in herd B, a single G-type was identified. The serotype G10 and the
      electropherotype persisted over time in herd A. No characteristic G-type
      variation in the geographic distribution of cattle herds in herd B was obvious.
      There was no difference in the G-type distributions between the strains from
      clinically and subclinically rotavirus-infected calves in dairy herd A. The
      results from this study strongly indicate a pronounced stability in the rotavirus
      G-type distribution in Swedish cattle herds, which emphasizes the importance of
      continuous preventive measures for control of neonatal calf diarrhea. A future
      bovine rotavirus vaccine in Sweden should contain G10 and G6 strains.

PMID- 10066652
TI  - Protection against influenza virus infection of mice fed Bifidobacterium breve
      YIT4064.
AB  - Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus
      were more strongly protected against influenza virus infection of the lower
      respiratory tract than ones immunized with influenza virus only. The number of
      mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral
      administration of B. breve YIT4064 and oral immunization with influenza virus was
      significantly greater than that upon oral immunization with influenza virus only.
      These findings demonstrated that the oral administration of B. breve YIT4064
      increased anti-influenza virus IgG antibodies in serum and protected against
      influenza virus infection. The oral administration of B. breve YIT4064 may
      enhance antigen-specific IgG against various pathogenic antigens taken orally and
      induce protection against various virus infections.

PMID- 10066653
TI  - Increased expression of regeneration and tolerance factor in individuals with
      human immunodeficiency virus infection.
AB  - Regeneration and tolerance factor (RTF) plays a pivotal role in successful
      pregnancy outcome and has potent immunomodulating properties. During pregnancy,
      it is abundantly expressed in the placenta and on peripheral B lymphocytes.
      Several lines of evidence suggest that both successful pregnancy outcome and
      progression from human immunodeficiency virus (HIV) infection to AIDS are
      associated with a Th2-type response. As a result, we hypothesized that the
      cellular expression of RTF may also be increased during infection with HIV. Using
      flow cytometric analysis, we showed a significantly (P < 0.01) increased
      expression of RTF on CD3(+) cells obtained from individuals with HIV over that
      for individuals without HIV. On average, 32.1% of the CD3(+) cells from
      individuals with HIV expressed high levels of RTF. In contrast, an average of
      only 6.7% of the CD3(+) cells from individuals without HIV expressed high levels
      of RTF. Similar results were obtained when CD19(+) cells from individuals with
      (mean, 44.1%) and without (mean, 25.8%) HIV were evaluated. Linear regression
      analysis suggested that high levels of RTF expression by CD3(+) cells correlated
      better with viral load (r value, 0.46) than with absolute CD4 count (r value,
      0.09). While additional experiments are necessary to delineate the precise
      immunologic role of RTF, our current data suggest that RTF expression during HIV
      infection may be a useful marker of immune activation.

PMID- 10066654
TI  - Contributory and exacerbating roles of gaseous ammonia and organic dust in the
      etiology of atrophic rhinitis.
AB  - Pigs reared commercially indoors are exposed to air heavily contaminated with
      particulate and gaseous pollutants. Epidemiological surveys have shown an
      association between the levels of these pollutants and the severity of lesions
      associated with the upper respiratory tract disease of swine atrophic rhinitis.
      This study investigated the role of aerial pollutants in the etiology of atrophic
      rhinitis induced by Pasteurella multocida. Forty, 1-week-old Large White piglets
      were weaned and divided into eight groups designated A to H. The groups were
      housed in Rochester exposure chambers and continuously exposed to the following
      pollutants: ovalbumin (groups A and B), ammonia (groups C and D), ovalbumin plus
      ammonia (groups E and F), and unpolluted air (groups G and H). The concentrations
      of pollutants used were 20 mg m-3 total mass and 5 mg m-3 respirable mass for
      ovalbumin dust and 50 ppm for ammonia. One week after exposure commenced, the
      pigs in groups A, C, E, and G were infected with P. multocida type D by
      intranasal inoculation. After 4 weeks of exposure to pollutants, the pigs were
      killed and the extent of turbinate atrophy was assessed with a morphometric index
      (MI). Control pigs kept in clean air and not inoculated with P. multocida (group
      H) had normal turbinate morphology with a mean MI of 41.12% (standard deviation
      [SD], +/- 1. 59%). In contrast, exposure to pollutants in the absence of P.
      multocida (groups B, D, and F) induced mild turbinate atrophy with mean MIs of
      49.65% (SD, +/-1.96%), 51.04% (SD, +/-2.06%), and 49.88% (SD, +/-3.51%),
      respectively. A similar level of atrophy was also evoked by inoculation with P.
      multocida in the absence of pollutants (group G), giving a mean MI of 50.77% (SD,
      +/-2.07%). However, when P. multocida inoculation was combined with pollutant
      exposure (groups A, C, and E) moderate to severe turbinate atrophy occurred with
      mean MIs of 64.93% (SD, +/-4.64%), 59.18% (SD, +/-2.79%), and 73.30% (SD, +/
      3.19%), respectively. The severity of atrophy was greatest in pigs exposed
      simultaneously to dust and ammonia. At the end of the exposure period, higher
      numbers of P. multocida bacteria were isolated from the tonsils than from the
      nasal membrane, per gram of tissue. The severity of turbinate atrophy in
      inoculated pigs was proportional to the number of P. multocida bacteria isolated
      from tonsils (r2 = 0.909, P < 0.05) and nasal membrane (r2 = 0.628, P < 0.05).
      These findings indicate that aerial pollutants contribute to the severity of
      lesions associated with atrophic rhinitis by facilitating colonization of the
      pig's upper respiratory tract by P. multocida and also by directly evoking mild
      atrophy.

PMID- 10066655
TI  - Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity,
      nutritional status, and vitamin A therapy.
AB  - Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the
      membrane-bound form of CD30, a putative marker of type 2 cytokine-producing
      cells. We measured sCD30 levels in children with tuberculosis, a disease
      characterized by prominent type 1 lymphocyte cytokine responses. We postulated
      that disease severity and nutritional status would alter cytokine responses and
      therefore sCD30 levels. Samples from South African children enrolled
      prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients
      were originally enrolled in a randomized, double-blind placebo-controlled study
      of the effects of oral vitamin A supplementation on prognosis of tuberculosis.)
      Plasma samples collected at the time of diagnosis and 6 and 12 weeks later
      (during antituberculosis therapy) were analyzed. sCD30 levels were measured by
      enzyme immunoassay. The 91 children included in the study demonstrated high
      levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter).
      Although there was a trend toward higher sCD30 levels in more severe disease
      (e.g., culture-positive disease or miliary disease), this was not statistically
      significant. Significantly higher sCD30 levels were demonstrated in the presence
      of nutritional compromise: the sCD30 level was higher in patients with a weight
      below the third percentile for age, in those with clinical signs of kwashiorkor,
      and in those with a low hemoglobin content. There was minimal change in the sCD30
      level after 12 weeks of therapy, even though patients improved clinically.
      However, changes in sCD30 after 12 weeks differed significantly when 46 patients
      (51%) who received vitamin A were compared with those who had received a placebo.
      Vitamin A-supplemented children demonstrated a mean (+/- standard error of the
      mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a
      factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P =
      0.02). We conclude that children with tuberculosis had high sCD30 levels, which
      may reflect the presence of a type 2 cytokine response. Nutritional compromise
      was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation
      of sCD30 levels over time.

PMID- 10066656
TI  - Potential value of major antigenic protein 2 for serological diagnosis of
      heartwater and related ehrlichial infections.
AB  - Cowdria ruminantium is the etiologic agent of heartwater, a disease causing major
      economic loss in ruminants in sub-Saharan Africa and the Caribbean. Development
      of a serodiagnostic test is essential for determining the carrier status of
      animals from regions where heartwater is endemic, but most available tests give
      false-positive reactions with sera against related Erhlichia species. Current
      approaches rely on molecular methods to define proteins and epitopes that may
      allow specific diagnosis. Two major antigenic proteins (MAPs), MAP1 and MAP2,
      have been examined for their use as antigens in the serodiagnosis of heartwater.
      The objectives of this study were (i) to determine if MAP2 is conserved among
      five geographically divergent strains of C. ruminantium and (ii) to determine if
      MAP2 homologs are present in Ehrlichia canis, the causative agent of canine
      ehrlichiosis, and Ehrlichia chaffeensis, the organism responsible for human
      monocytic ehrlichiosis. These two agents are closely related to C. ruminantium.
      The map2 gene from four strains of C. ruminantium was cloned, sequenced, and
      compared with the previously reported map2 gene from the Crystal Springs strain.
      Only 10 nucleic acid differences between the strains were identified, and they
      translate to only 3 amino acid changes, indicating that MAP2 is highly conserved.
      Genes encoding MAP2 homologs from E. canis and E. chaffeensis also were cloned
      and sequenced. Amino acid analysis of MAP2 homologs of E. chaffeensis and E.
      canis with MAP2 of C. ruminantium revealed 83.4 and 84.4% identities,
      respectively. Further analysis of MAP2 and its homologs revealed that the whole
      protein lacks specificity for heartwater diagnosis. The development of epitope
      specific assays using this sequence information may produce diagnostic tests
      suitable for C. ruminantium and also other related rickettsiae.

PMID- 10066657
TI  - Human herpesviruses in chronic fatigue syndrome.
AB  - We have conducted a double-blind study to assess the possible involvement of the
      human herpesviruses (HHVs) HHV6, HHV7, Epstein-Barr virus (EBV), and
      cytomegalovirus in chronic fatigue syndrome (CFS) patients compared to age-, race
      , and gender-matched controls. The CFS patient population was composed of
      rigorously screened civilian and Persian Gulf War veterans meeting the Centers
      for Disease Control and Prevention's CFS case definition criteria. Healthy
      control civilian and veteran populations had no evidence of CFS or any other
      exclusionary medical or psychiatric condition. Patient peripheral blood
      mononuclear cells were analyzed by PCR for the presence of these HHVs. Using two
      tailed Fisher's exact test analyses, we were unable to ascertain any
      statistically significant differences between the CFS patient and control
      populations in terms of the detection of one or more of these viruses. This
      observation was upheld when the CFS populations were further stratified with
      regard to the presence or absence of major axis I psychopathology and patient
      self-reported gradual versus acute onset of disease. In tandem, we performed
      serological analyses of serum anti-EBV and anti-HHV6 antibody titers and found no
      significant differences between the CFS and control patients.

PMID- 10066658
TI  - Genetic and serological analysis of lipoprotein LppA in Mycoplasma mycoides
      subsp. mycoides LC and Mycoplasma mycoides subsp. capri.
AB  - The genes encoding the 62-kDa lipoproteins from the Mycoplasma mycoides subsp.
      mycoides large-colony type (LC) strain Y-goat and the M. mycoides subsp. capri
      strain PG3 were cloned and analyzed by sequencing. These two lipoproteins have
      been named LppA[MmymyLC] and LppA[Mmyca], and their corresponding genes have been
      named lppA[MmymyLC] and lppA[Mmyca], respectively. The nucleotide and deduced
      amino acid sequences of these two lipoproteins showed a very high degree of
      similarity between these two mycoplasmas. Given the sequence data, LppA seems to
      fulfill the same structural functions as the previously described major
      lipoproteins P72 of M. mycoides subsp. mycoides small-colony type and P67 of the
      Mycoplasma species bovine group 7. Based on lppA gene sequences of M. mycoides
      subsp. mycoides LC and M. mycoides subsp. capri type strains, a specific PCR
      assay was developed so that it amplified this gene in all field strains of the
      two species analyzed in this study but not in the other members of the M.
      mycoides cluster. Analysis of the PCR-amplified lppA genes with frequently
      cutting restriction enzymes showed a certain degree of genetic variability which,
      however, did not cluster the two subspecies. This PCR therefore allows a rapid
      identification of M. mycoides subsp. mycoides LC and M. mycoides subsp. capri but
      does not distinguish between these two closely related subspecies. LppA was
      expressed in Escherichia coli K-12 and used for the production of polyclonal
      mouse antiserum. Antibodies against recombinant LppA[MmymyLC] reacted with a 62
      kDa protein in all M. mycoides subsp. mycoides LC and M. mycoides subsp. capri
      type strains and field strains tested but not with the other members of the M.
      mycoides cluster, thus showing the antigenic specificity of LppA and further
      supporting the concept that a close relationship exists between these two
      mycoplasmas.

PMID- 10066659
TI  - Immunoglobulin subclass distribution and diagnostic value of Leishmania donovani
      antigen-specific immunoglobulin G3 in Indian kala-azar patients.
AB  - Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains
      problematic, as early diagnosis is difficult and treatment often results in drug
      resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent
      assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect
      specific antibody responses in 25 untreated Indian visceral leishmaniasis
      patients. To investigate the pathogenetic significance of isotype markers in kala
      azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG
      subclasses were analyzed under clinically established diseased conditions. Since
      LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin
      isotype responses were evaluated, with LAg as antigen. Compared to 60 controls,
      which included patients with malaria, tuberculosis, leprosy, and typhoid and
      healthy subjects, visceral leishmaniasis patients showed significantly higher IgG
      (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and
      IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral
      leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from
      patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were
      significantly higher in visceral leishmaniasis patients than in the controls.
      IgG2 response, however, was significantly higher (twofold) in leprosy than even
      visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 =
      IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 >
      IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the
      potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.

PMID- 10066660
TI  - Specific enzyme-linked immunosorbent assays for quantitation of antibody-cytokine
      fusion proteins.
AB  - Preliminary testing has shown in vitro and in vivo that antitumor activity can be
      obtained with fusion proteins linking tumor-reactive monoclonal antibodies to
      cytokines, such as granulocyte-macrophage colony-stimulating factor or
      interleukin 2 (IL-2). Preclinical and clinical testing of these reagents requires
      their in vitro and in vivo quantitation and pharmacokinetic evaluation. We have
      focused on the detection of a fusion protein which links one human IL-2 molecule
      to the carboxy terminus of each heavy chain of the tumor-reactive human-mouse
      chimeric anti-GD2 antibody, ch14.18. We have developed enzyme-linked
      immunosorbent assays (ELISAs) to evaluate intact tumor-reactive fusion proteins.
      By these ELISAs we can reliably measure nanogram quantities of intact ch14.18-IL
      2 fusion protein and distinguish the intact protein from its components (ch14.18
      and IL-2) in buffer, mouse serum, and human serum with specificity and
      reproducibility. The measurement of intact ch14.18-IL-2 fusion protein is not
      confounded by free IL-2 or free ch14.18 when 100 ng or less of total
      immunoglobulin per ml is used during the assay procedure. Our results indicate
      that these ELISAs are suitable for preclinical and clinical testing and with
      slight modifications are applicable to the analysis of a variety of other fusion
      proteins.

PMID- 10066661
TI  - A powerful DNA extraction method and PCR for detection of microsporidia in
      clinical stool specimens.
AB  - The diagnosis of intestinal microsporidiosis has traditionally depended on direct
      visualization of the parasite in stool specimens or intestinal biopsy samples by
      light and/or electron microscopy. Limited information about the specificity and
      sensitivity of PCR for the detection microsporidia in clinical stool specimens is
      available. To establish a sensitive and specific method for the detection of
      microsporidia in clinical samples, we studied clinical stool specimens of 104
      randomly selected human immunodeficiency virus-infected patients with diarrhea to
      compare light microscopy and PCR. Fluorochrome Uvitex 2B staining was used for
      light microscopy. To raise the sensitivity of PCR, we used a powerful and fast
      DNA extraction method including stool sedimentation, glass bead disruption, and
      proteinase K and chitinase digestion. PCR was performed with primer pairs V1
      PMP2, V1-EB450, and V1-SI500, and the nature of the PCR products was confirmed by
      Southern blot hybridization. Microsporidiosis was diagnosed by light microscopy
      in eight patients. Ten patients tested positive for microsporidiosis by PCR.
      Enterocytozoon bieneusi was found in seven cases, and Encephalitozoon
      intestinalis was found in four cases. In one case a double infection with E.
      bieneusi and E. intestinalis was diagnosed by PCR, whereas light microscopy
      showed only E. bieneusi infection. PCR testing of stool specimens is useful for
      diagnosis and species differentiation of intestinal microsporidiosis in HIV
      patients.

PMID- 10066662
TI  - Predictive value of CD19 measurements for bacterial infections in children
      infected with human immunodeficiency virus.
AB  - We investigated the predictive value of CD19 cell percentages (CD19%) for times
      to bacterial infections, using data from six pediatric AIDS Clinical Trials Group
      protocols and adjusting for other potentially prognostic variables, such as CD4%,
      CD8%, immunoglobulin (IgA) level, lymphocyte count, prior infections, prior
      zidovudine treatment, and age. In addition, we explored the combined effects of
      CD19% and IgG level in predicting time to infection. We found that a low CD19% is
      associated with a nonsignificant 1.2-fold increase in hazard of bacterial
      infection (95% confidence interval: 0.97, 1.49). In contrast, a high IgG level is
      associated with a nonsignificant 0.87-fold decrease in hazard of infection (95%
      confidence interval: 0.68, 1.12). CD4% was more prognostic of time to bacterial
      infection than CD19% or IgG level. Low CD19% and high IgG levels together lead to
      a significant (P < 0. 01) 0.50-fold decrease in hazard (95% confidence interval:
      0.35, 0. 73) relative to low CD19% and low IgG levels. Similarly, in a model
      involving assay result changes (from baseline to 6 months) as well as baseline
      values, the effect of CD19% by itself is reversed from its effect in conjunction
      with IgG. In this model, CD19% that are increasing and high are associated with
      decreases in hazard of infection (P < 0.01), while increasing CD19% and
      increasing IgG levels are associated with significant (at the P = 0.01 level)
      fourfold increases in hazard of infection relative to stable CD19% and
      decreasing, stable, or increasing IgG levels. Our data suggest that CD19%, in
      conjunction with IgG level, provides a useful prognostic tool for bacterial
      infections. It is highly likely that T-helper function impacts on B-cell
      function; thus, inclusion of CD4% in such analyses may greatly enhance the
      assessment of risk for bacterial infection.

PMID- 10066663
TI  - Alloreactivity and association of human natural killer cells with the major
      histocompatibility complex.
AB  - All NK cells potentially lytic for autologous cells but not expressing self-major
      histocompatibility complex (MHC)-reactive receptors could be eliminated by a
      negative selection mechanism during ontogeny. This idea is based on the existence
      of a NK cell subset expressing a specific inhibitory receptor for allogeneic MHC
      alleles. As ancestral haplotypes of the MHC appear to define identical MHC
      haplotypes in unrelated individuals, unrelated individuals having the same
      ancestral haplotype should also have the same NK-defined allospecificities that
      have been shown to map to the human MHC. To test this prediction, multiple cell
      lines from unrelated individuals having the same ancestral haplotypes were tested
      for the NK-defined allospecificities. It was found that cells having the same
      ancestral haplotypes do have the same NK-defined specificities. Furthermore, the
      NK-defined phenotype of cells that possess two different ancestral haplotypes can
      be predicted from the NK-defined phenotypes of unrelated cells that are
      homozygous for the ancestral haplotypes concerned. Although the group 1 and 2 NK
      defined allospecificities can be explained to some extent by HLA-C alleles,
      evidence is presented that additional genes may modify the phenotype conferred by
      HLA-C.

PMID- 10066664
TI  - Cytokines and inflammatory mediators do not indicate acute infection in cystic
      fibrosis.
AB  - Various treatment regimens and difficulties with research design are encountered
      with cystic fibrosis (CF) because no standard diagnostic criteria exist for
      defining acute respiratory exacerbations. This study evaluated the role of serial
      monitoring of concentrations of selected cytokines and inflammatory mediators in
      serum and sputum as predictors of respiratory exacerbation, as useful outcome
      measures for CF, and to guide therapy. Interleukin-8 (IL-8), tumor necrosis
      factor alpha (TNF-alpha), neutrophil elastase-alpha-1-protease inhibitor complex
      (NE complex), protein, and alpha-1-protease inhibitor (alpha-1-PI) were measured
      in serum and sputum collected from CF patients during respiratory exacerbations
      and periods of well-being. Levels of NE complex, protein, and alpha-1-PI in
      sputum rose during respiratory exacerbations and fell after institution of
      antibiotic therapy (P = 0.078, 0.001, and 0.002, respectively). Mean (+/-
      standard error of the mean) levels of IL-8 and TNF-alpha were extremely high in
      sputum (13,780 +/- 916 and 249.4 +/- 23.5 ng/liter, respectively) but did not
      change significantly with clinical deterioration of the patient (P > 0.23). IL-8
      and TNF-alpha were generally undetectable in serum, and therefore these measures
      were unhelpful. Drop in forced expiratory volume in 1 s was the only clinical or
      laboratory parameter that was close to being a determinant of respiratory
      exacerbation (P = 0.055). This study provides evidence of intense immunological
      activity occurring continually within the lungs of adult CF patients. Measurement
      of cytokines and inflammatory mediators in CF sputum is not helpful for
      identifying acute respiratory exacerbations.

PMID- 10066665
TI  - Variants of a Cryptococcus neoformans strain elicit different inflammatory
      responses in mice.
AB  - The virulence of Cryptococcus neoformans isolates with high and low extracellular
      proteolytic activity was investigated in mice. No consistent relationship between
      proteolytic activity and virulence was observed, but isolates derived from one
      strain were shown to elicit different inflammatory responses.

PMID- 10066666
TI  - Performance of competitive and indirect enzyme-linked immunosorbent assays, gel
      immunoprecipitation with native hapten polysaccharide, and standard serological
      tests in diagnosis of sheep brucellosis.
AB  - Competitive and standard enzyme-linked immunosorbent assays (ELISAs), rose bengal
      (RB), complement fixation, and agar gel immunoprecipitation with native hapten
      (AGID-NH) were compared by using sera from Brucella-free, Brucella melitensis
      infected, and B. melitensis Rev1-vaccinated sheep. The most sensitive tests were
      indirect ELISA and RB, and the most specific tests were AGID-NH and competitive
      ELISA. We show that RB followed by AGID-NH is a simple and effective system for
      diagnosing sheep brucellosis.

PMID- 10066667
TI  - A murine model of renal abscess formation.
AB  - We developed a murine model of kidney abscess by direct renal injection of either
      Escherichia coli (1 x 10(6) to 7 x 10(6) organisms) or sterile medium. Bacterial
      infection produced renal abscesses, bacteremia, and late-onset leukocytosis in
      all animals. Controls were unaffected. This model may be useful for the study of
      various sequelae of kidney infection.

PMID- 10066668
TI  - Phagocytosis of Vibrio cholerae O139 Bengal by human polymorphonuclear
      leukocytes.
AB  - Capsulated bacteria exhibit serum (complement) resistance and resistance to
      phagocytosis, which result in disseminated infections. Vibrio cholerae O139
      strains possess a thin capsule and have been found to be partially serum
      resistant in a previous study. In the present study, compared to a standard
      capsulated Klebsiella pneumoniae strain, which showed total resistance to killing
      by phagocytosis, V. cholerae O139 strains were shown to be only partially
      resistant, with most strains showing <40% survival. These findings may explain
      the relative rarity of V. cholerae O139 bacteremia in cholera caused by this
      organism.

PMID- 10066669
TI  - Restricted isotypic antibody reactivity to hepatitis C virus synthetic peptides
      in immunocompromised patients.
AB  - An enzyme immunoassay based on three synthetic peptides from the core, NS4, and
      NS5 regions of hepatitis C virus allowed the detection of antibodies in 100% of
      immunocompetent infected patients and in 91% of immunocompromised patients
      (hemodialysis and hemophiliac patients). Immune impairment seemed to restrict the
      spectrum of antibody isotypes reacting to the core peptide.

PMID- 10066670
TI  - Alteration of endothelium-dependent hyperpolarizations in porcine coronary
      arteries with regenerated endothelium.
AB  - The present study was designed to test the ability of regenerated endothelium to
      evoke endothelium-dependent hyperpolarizations. Hyperpolarizations induced by
      serotonin and bradykinin were compared in isolated porcine coronary arteries with
      native or regenerated endothelium, 4 weeks after balloon endothelial denudation.
      The experiments were performed in the presence of inhibitors of nitric oxide
      synthase (Nomega-nitro-L-arginine) and cyclooxygenase (indomethacin). The
      transmembrane potential was measured using conventional glass microelectrodes.
      Smooth muscle cells from coronary arteries with regenerated endothelium were
      depolarized in comparison with control coronary arteries from the same hearts.
      Spontaneous membrane potential oscillations of small amplitude or spikes were
      observed in some of these arteries but never in arteries with native endothelium.
      In coronary arteries from control pigs, both serotonin and bradykinin induced
      concentration-dependent hyperpolarizations. In the presence of ketanserin, 10
      micromol/L serotonin induced a transient hyperpolarization in control coronary
      arteries. Four weeks after balloon denudation, the response to serotonin was
      normal in arteries with native endothelium, but the hyperpolarization was
      significantly lower in coronary arteries with regenerated endothelium. In control
      arteries, the endothelium-dependent hyperpolarization obtained with bradykinin
      (30 nmol/L) was reproducible. Four weeks after balloon denudation, comparable
      hyperpolarizations were obtained in coronary arteries with native endothelium. By
      contrast, in arteries with regenerated endothelium, the hyperpolarization to
      bradykinin became voltage-dependent. In the most depolarized cells, the
      hyperpolarization to bradykinin was augmented. The changes in resting membrane
      potential and the alteration in endothelium-dependent hyperpolarizations observed
      in the coronary arteries with regenerated endothelium may contribute to the
      reduced response to serotonin and the unchanged relaxation to bradykinin
      described previously.

PMID- 10066671
TI  - Balloon-artery interactions during stent placement: a finite element analysis
      approach to pressure, compliance, and stent design as contributors to vascular
      injury.
AB  - Endovascular stents expand the arterial lumen more than balloon angioplasty and
      reduce rates of restenosis after coronary angioplasty in selected patients.
      Understanding the factors involved in vascular injury imposed during stent
      deployment may allow optimization of stent design and stent-placement protocols
      so as to limit vascular injury and perhaps reduce restenosis. Addressing the
      hypothesis that a previously undescribed mechanism of vascular injury during
      stent deployment is balloon-artery interaction, we have used finite element
      analysis to model how balloon-artery contact stress and area depend on stent
      strut geometry, balloon compliance, and inflation pressure. We also examined
      superficial injury during deployment of stents of varied design in vivo and in a
      phantom model ex vivo to show that balloon-induced damage can be modulated by
      altering stent design. Our results show that higher inflation pressures, wider
      stent-strut openings, and more compliant balloon materials cause markedly larger
      surface-contact areas and contact stresses between stent struts. Appreciating
      that the contact stress and contact area are functions of placement pressure,
      stent geometry, and balloon compliance may help direct development of novel stent
      designs and stent-deployment protocols so as to minimize vascular injury during
      stenting and perhaps to optimize long-term outcomes.

PMID- 10066672
TI  - Endothelial implants inhibit intimal hyperplasia after porcine angioplasty.
AB  - The perivascular implantation of tissue-engineered endothelial cells around
      injured arteries offers an opportunity to study fundamental vascular physiology
      as well as restore and improve tissue function. Cell source is an important issue
      because the ability to implant either xenogeneic or allogeneic cells would
      greatly enhance the clinical applications of tissue-engineered grafts. We
      investigated the biological and immunological responses to endothelial cell
      xenografts and allografts in pigs 4 weeks after angioplasty of the carotid
      arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam
      matrices and implanted in the perivascular space of 42 injured arteries. Both
      porcine and bovine endothelial cell grafts reduced the restenosis index compared
      with control by 54% and 46%, respectively. Perivascular heparin release devices,
      formulated to release heparin at twice the rate of release of heparan sulfate
      proteoglycan from endothelial cell implants, produced no significant reduction in
      the restenosis index. Endothelial cell implants also reduced occlusive thrombosis
      compared with control and heparin release devices. Host immune responses to
      endothelial implants were investigated by immunohistochemical examination of
      explanted devices and by immunocytochemistry of serum samples. The bovine cell
      grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes,
      and caused an increase in antibodies detected in serum samples. Reduced cellular
      infiltration and no humoral response were detected in animals that received
      allografts. Despite the difference in immune response, the biological effects of
      xenografts or allografts did not differ significantly.

PMID- 10066673
TI  - Tumor necrosis factor-alpha contributes to ischemia- and reperfusion-induced
      endothelial activation in isolated hearts.
AB  - -During myocardial reperfusion, polymorphonuclear neutrophil (PMN) adhesion
      involving the intercellular adhesion molecule-1 (ICAM-1) may lead to aggravation
      and prolongation of reperfusion injury. We studied the role of early tumor
      necrosis factor-alpha (TNF-alpha) cleavage and nuclear factor-kappaB (NF-kappaB)
      activation on ICAM-1 expression and venular adhesion of PMN in isolated hearts
      after ischemia (15 minutes) and reperfusion (30 to 480 minutes). NF-kappaB
      activation (electromobility shift assay) was found after 30 minutes of
      reperfusion and up to 240 minutes. ICAM-1 mRNA, assessed by Northern blot,
      increased during the same interval. Functional effect of newly synthesized
      adhesion molecules was found by quantification (in situ fluorescence microscopy)
      of PMN, given as bolus after ischemia, which became adherent to small coronary
      venules (10 to 50 microm in diameter). After 480 minutes of reperfusion, ICAM-1
      dependent PMN adhesion increased 2.5-fold compared with PMN adhesion obtained
      during acute reperfusion. To study the influence of NF-kappaB on PMN adhesion, we
      inhibited NF-kappaB activation by transfection of NF-kappaB decoy
      oligonucleotides into isolated hearts using HJV-liposomes. Decoy NF-kappaB but
      not control oligonucleotides blocked ICAM-1 upregulation and inhibited the
      subacute increase in PMN adhesion. Similar effects were obtained using BB 1101
      (10 microg), an inhibitor of TNF-alpha cleavage enzyme. These data suggest that
      ischemia and reperfusion in isolated hearts cause liberation of TNF-alpha,
      activation of NF-kappaB, and upregulation of ICAM-1, an adhesion molecule
      involved in inflammatory response after ischemia and reperfusion.

PMID- 10066674
TI  - Regulation of myocardial blood flow by oxygen consumption is maintained in the
      failing heart during exercise.
AB  - The hemodynamic abnormalities and neurohumoral activation that accompany
      congestive heart failure (CHF) might be expected to impair the increase in
      coronary blood flow that occurs during exercise. This study was performed to
      determine the effects of CHF on myocardial oxygen consumption and coronary blood
      flow during exercise. Coronary blood flow was measured in chronically
      instrumented dogs at rest, during 2 stages of graded treadmill exercise under
      control conditions (n=10), and after the development of CHF produced by 3 weeks
      of rapid ventricular pacing (n=9). In the normal dogs, coronary blood flow
      increased during exercise in proportion to the increase in the heart rate x the
      left ventricular systolic blood pressure product (RPP). After the development of
      CHF, resting myocardial blood flow was 25% lower than normal (P<0.05). Myocardial
      blood flow increased during the first stage of exercise, but then failed to
      increase further during the second stage of exercise despite an additional
      increase in the RPP. Myocardial oxygen consumption during exercise was
      significantly lower in animals with CHF and paralleled coronary flow. Despite the
      lower values for coronary blood flow in animals with CHF, there was no evidence
      for myocardial ischemia. Thus, even during the second level of exercise when
      coronary flow failed to increase, myocardial lactate consumption continued and
      coronary venous pH did not fall. In addition, the failure of coronary flow to
      increase as the exercise level was increased from stage 1 to stage 2 was not
      associated with a further increase in myocardial oxygen extraction. Thus, cardiac
      failure was associated with decreased myocardial oxygen consumption and failure
      of oxygen consumption to increase with an increase in the level of exercise. This
      abnormality did not appear to result from inadequate oxygen availability, but
      more likely represented a reduction of myocardial oxygen usage with a secondary
      decrease in metabolic coronary vasodilation.

PMID- 10066675
TI  - Homocysteine enhances neutrophil-endothelial interactions in both cultured human
      cells and rats In vivo.
AB  - Despite intense investigation, mechanisms linking the development of occlusive
      vascular disease with elevated levels of homocysteine (HCY) are still unclear.
      The vascular endothelium plays a key role in regulating thrombogenesis and
      thrombolysis. We hypothesized that vascular lesions in individuals with elevated
      plasma HCY may be related to a dysfunction of the endothelium triggered by HCY.
      We investigated the effect of HCY on human neutrophil adhesion to and migration
      through endothelial monolayers. We also examined the effect of HCY on leukocyte
      adhesion and migration in mesenteric venules of anesthetized rats. We found that
      pathophysiological concentrations of HCY in vitro induce increased adhesion
      between neutrophils and endothelial cells. This contact results in neutrophil
      migration across the endothelial layer, with concurrent damage and detachment of
      endothelial cells. In vivo, HCY infused in anesthetized rats caused parallel
      effects, increasing leukocyte adhesion to and extravasation from mesenteric
      venules. Our results suggest that extracellular H2O2, generated by adherent
      neutrophils and/or endothelial cells, is involved in the in vitro endothelial
      cell damage. The possibility exists that leukocyte-mediated changes in
      endothelial integrity and function may lead to the vascular disease seen in
      individuals with elevated plasma HCY.

PMID- 10066676
TI  - Regulation of sympathetic nerve activity in heart failure: a role for nitric
      oxide and angiotensin II.
AB  - The mechanisms by which sympathetic function is augmented in chronic heart
      failure (CHF) are not well understood. A previous study from this laboratory
      (Circ Res. 1998;82:496-502) indicated that blockade of nitric oxide (NO)
      synthesis resulted in only an increase in renal sympathetic nerve activity (RSNA)
      when plasma angiotensin II (Ang II) levels were elevated. The present study was
      undertaken to determine if NO reduces RSNA in rabbits with CHF when Ang II
      receptors are blocked. Twenty-four New Zealand White rabbits were instrumented
      with cardiac dimension crystals, a left ventricular pacing lead, and a pacemaker.
      After pacing at 360 to 380 bpm for approximately 3 weeks, a renal sympathetic
      nerve electrode and arterial and venous catheters were implanted. Studies were
      carried out in the conscious state 3 to 7 days after electrode implantation. The
      effects of a 1-hour infusion of sodium nitroprusside (SNP; 3 microgram . kg-1.
      min-1) on RSNA and mean arterial pressure (MAP) were determined before and after
      Ang II blockade with losartan (5 mg/kg) in normal and CHF rabbits. Changes in MAP
      were readjusted to normal with phenylephrine. Before losartan, SNP evoked a
      decrease in MAP and an increase in RSNA in both groups that was baroreflex
      mediated, because both MAP and RSNA returned to control when phenylephrine was
      administered. In the normal group, losartan plus SNP caused a reduction in MAP
      and an increase in RSNA that was 152.6+/-9.8% of control. Phenylephrine returned
      both MAP and RSNA back to the control levels. However, in the CHF group, losartan
      plus SNP evoked a smaller change in RSNA for equivalent changes in MAP (117.1+/
      4.1% of control). On returning MAP to the control level with phenylephrine, RSNA
      was reduced to 65.2+/-2.9% of control (P<0. 0001). These data suggest that
      endogenous Ang II contributes to the sympathoexcitation in the CHF state and that
      blockade of Ang II receptors plus providing an exogenous source of NO reduces
      RSNA below the elevated baseline levels. We conclude that both a loss of NO and
      an increase in Ang II are necessary for sustained increases in sympathetic nerve
      activity in the CHF state.

PMID- 10066677
TI  - Cellular mechanisms of altered contractility in the hypertrophied heart: big
      hearts, big sparks.
AB  - To investigate the cellular mechanisms for altered Ca2+ homeostasis and
      contractility in cardiac hypertrophy, we measured whole-cell L-type Ca2+ currents
      (ICa,L), whole-cell Ca2+ transients ([Ca2+]i), and Ca2+ sparks in ventricular
      cells from 6-month-old spontaneously hypertensive rats (SHRs) and from age- and
      sex-matched Wistar-Kyoto and Sprague-Dawley control rats. By echocardiography,
      SHR hearts had cardiac hypertrophy and enhanced contractility (increased
      fractional shortening) and no signs of heart failure. SHR cells had a voltage
      dependent increase in peak [Ca2+]i amplitude (at 0 mV, 1330+/-62 nmol/L [SHRs]
      versus 836+/-48 nmol/L [controls], P<0.05) that was not associated with changes
      in ICa,L density or kinetics, resting [Ca2+]i, or Ca2+ content of the
      sarcoplasmic reticulum (SR). SHR cells had increased time of relaxation. Ca2+
      sparks from SHR cells had larger average amplitudes (173+/-192 nmol/L [SHRs]
      versus 109+/-64 nmol/L [control]; P<0.05), which was due to redistribution of
      Ca2+ sparks to a larger amplitude population. This change in Ca2+ spark amplitude
      distribution was not associated with any change in the density of ryanodine
      receptors, calsequestrin, junctin, triadin 1, Ca2+-ATPase, or phospholamban.
      Therefore, SHRs with cardiac hypertrophy have increased contractility, [Ca2+]i
      amplitude, time to relaxation, and average Ca2+ spark amplitude ("big sparks").
      Importantly, big sparks occurred without alteration in the trigger for SR Ca2+
      release (ICa,L), SR Ca2+ content, or the expression of several SR Ca2+-cycling
      proteins. Thus, cardiac hypertrophy in SHRs is linked with an alteration in the
      coupling of Ca2+ entry through L-type Ca2+ channels and the release of Ca2+ from
      the SR, leading to big sparks and enhanced contractility. Alterations in the
      microdomain between L-type Ca2+ channels and SR Ca2+ release channels may
      underlie the changes in Ca2+ homeostasis observed in cardiac hypertrophy.
      Modulation of SR Ca2+ release may provide a new therapeutic strategy for cardiac
      hypertrophy and for its progression to heart failure and sudden death.

PMID- 10066678
TI  - The sarcoplasmic reticulum and the Na+/Ca2+ exchanger both contribute to the Ca2+
      transient of failing human ventricular myocytes.
AB  - Our objective was to determine the respective roles of the sarcoplasmic reticulum
      (SR) and the Na+/Ca2+ exchanger in the small, slowly decaying Ca2+ transients of
      failing human ventricular myocytes. Left ventricular myocytes were isolated from
      explanted hearts of patients with severe heart failure (n=18). Cytosolic Ca2+,
      contraction, and action potentials were measured by using indo-1, edge detection,
      and patch pipettes, respectively. Selective inhibitors of SR Ca2+ transport
      (thapsigargin) and reverse-mode Na+/Ca2+ exchange activity (No. 7943, Kanebo Ltd)
      were used to define the respective contribution of these processes to the Ca2+
      transient. Ca2+ transients and contractions induced by action potentials (AP
      transients) at 0.5 Hz exhibited phasic and tonic components. The duration of the
      tonic component was determined by the action potential duration. Ca2+ transients
      induced by caffeine (Caf transients) exhibited only a phasic component with a
      rapid rate of decay that was dependent on extracellular Na+. The SR Ca2+-ATPase
      inhibitor thapsigargin abolished the phasic component of the AP Ca2+ transient
      and of the Caf transient but had no significant effect on the tonic component of
      the AP transient. The Na+/Ca2+ exchange inhibitor No. 7943 eliminated the tonic
      component of the AP transient and reduced the magnitude of the phasic component.
      In failing human myocytes, Ca2+ transients and contractions exhibit an SR
      related, phasic component and a slow, reverse-mode Na+/Ca2+ exchange-related
      tonic component. These findings suggest that Ca2+ influx via reverse-mode
      Na+/Ca2+ exchange during the action potential may contribute to the slow decay of
      the Ca2+ transient in failing human myocytes.

PMID- 10066679
TI  - Proadrenomedullin N-terminal 20 peptide hyperpolarizes the membrane by activating
      an inwardly rectifying K+ current in differentiated PC12 cells.
AB  - The mechanism of proadrenomedullin N-terminal 20 peptide (PAMP)-induced
      inhibition of catecholamine release from adrenergic nerve was investigated in
      nerve growth factor-treated PC12 cells that have differentiated characteristics
      somewhat similar to noradrenergic neurons. The effect of PAMP on the excitability
      of these cells was investigated with the use of perforated whole-cell clamp. PAMP
      hyperpolarized the membrane by increasing a K+ conductance in a dose-dependent
      manner. The current-voltage relationship (I-V) relationship of the PAMP-induced
      K+ conductance exhibited inward-going rectification. The activation was abolished
      by microinjecting GDPbetaS into the cells or pretreating the cells with pertussis
      toxin. These results indicate that a pertussis toxin-sensitive G protein is
      involved in the signal transduction. The PAMP-induced activation of the K+
      conductance was attenuated by microinjecting antibody against the carboxyl
      terminus of Galphai3, but it was not influenced by microinjecting antibody
      against the common carboxyl termini of Galphai1 and Galphai2, which indicated
      that the G protein coupling the PAMP receptor to the inwardly rectifying K+
      current is Galphai3. The PAMP-induced hyperpolarization may inhibit the
      catecholamine release from the neurons by attenuating the action potential
      frequency.

PMID- 10066680
TI  - Mechanical stimulation regulates voltage-gated potassium currents in cardiac
      microvascular endothelial cells.
AB  - Vascular endothelial cells are constantly exposed to mechanical forces resulting
      from blood flow and transmural pressure. The goal of this study was to determine
      whether mechanical stimulation alters the properties of endothelial voltage-gated
      K+ channels. Cardiac microvascular endothelial cells (CMECs) were isolated from
      rat ventricular muscle and cultured on thin sheets of silastic membranes.
      Membrane currents were measured with the use of the whole-cell arrangement of the
      patch-clamp technique in endothelial cells subjected to static stretch for 24
      hours and compared with measurements from control, nonstretched cells. Voltage
      steps positive to -30 mV resulted in the activation of a time-dependent, delayed
      rectifier K+current (IK) in the endothelial cells. Mechanically induced increases
      of 97%, 355%, and 106% at +30 mV were measured in the peak amplitude of IK in
      cells stretched for 24 hours by 5%, 10%, and 15%, respectively. In addition, the
      half-maximal voltage required for IK activation was shifted from +34 mV in the
      nonstretched cells to -5 mV in the stretched cells. Although IK in both groups of
      CMECs was blocked to a similar extent by tetraethylammonium, currents in the
      stretched endothelial cells displayed an enhanced sensitivity to inhibition by
      charybdotoxin. Preincubation of the CMECs with either pertussis toxin or phorbol
      12-myristate 13-acetate during the 24 hours of cell stretch did not prevent the
      increase in IK. The application of phorbol 12-myristate 13-acetate and static
      stretch stimulated the proliferation of CMECs. Stretch-induced regulation of K+
      channels may be important to control the resting potential of the endothelium and
      may contribute to capillary growth during periods of mechanical perturbation.

PMID- 10066681
TI  - Rho family small G proteins play critical roles in mechanical stress-induced
      hypertrophic responses in cardiac myocytes.
AB  - -Mechanical stress induces a variety of hypertrophic responses, such as
      activation of protein kinases, reprogramming of gene expression, and an increase
      in protein synthesis. In the present study, to elucidate how mechanical stress
      induces such events, we examined the role of Rho family small GTP-binding
      proteins (G proteins) in mechanical stress-induced cardiac hypertrophy. Treatment
      of neonatal rat cardiomyocytes with the C3 exoenzyme, which abrogates Rho
      functions, suppressed stretch-induced activation of extracellular signal
      regulated protein kinases (ERKs). Overexpression of the Rho GDP dissociation
      inhibitor (Rho-GDI), dominant-negative mutants of RhoA (DNRhoA), or DNRac1
      significantly inhibited stretch-induced activation of transfected ERK2.
      Overexpression of constitutively active mutants of RhoA slightly activated ERK2
      in cardiac myocytes. Overexpression of C-terminal Src kinase, which inhibits
      functions of the Src family of tyrosine kinases, or overexpression of DNRas had
      no effect on stretch-induced activation of transfected ERK2. The promoter
      activity of skeletal alpha-actin and c-fos genes was increased by stretch, and
      these increases were completely inhibited by either cotransfection of Rho-GDI or
      pretreatment with C3 exoenzyme. Mechanical stretch increased phenylalanine
      incorporation into cardiac myocytes by approximately 1.5-fold compared with
      control, and this increase was also significantly suppressed by pretreatment with
      C3 exoenzyme. Overexpression of Rho-GDI or DNRhoA did not affect angiotensin II
      induced activation of ERK. ERKs were activated by culture media conditioned by
      stretch of cardiomyocytes without any treatment, but not of cardiomyocytes with
      pretreatment by C3 exoenzyme. These results suggest that the Rho family of small
      G proteins plays critical roles in mechanical stress-induced hypertrophic
      responses.

PMID- 10066682
TI  - alpha-adrenergic stimulation mediates glucose uptake through phosphatidylinositol
      3-kinase in rat heart.
AB  - We examined whether insulin and catecholamines share common pathways for their
      stimulating effects on glucose uptake. We perfused isolated working rat hearts
      with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/L, 0.05 microCi/mL)
      and sodium oleate (0.4 mmol/L). In the absence or presence of the
      phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin (3 micromol/L), we
      added insulin (1 mU/mL), epinephrine (1 micromol/L), phenylephrine (100
      micromol/L) plus propranolol (10 micromol/L, selective alpha-adrenergic
      stimulation), or isoproterenol (1 micromol/L) plus phentolamine (10 micromol/L,
      selective beta-adrenergic stimulation) to the perfusate. Cardiac power was found
      to be stable in all groups (between 8.07+/-0.68 and 10.7+/-0. 88 mW) and
      increased (25% to 47%) with addition of epinephrine, but not with selective alpha
      and beta-adrenergic stimulation. Insulin and epinephrine, as well as selective
      alpha- and beta-receptor stimulation, increased glucose uptake (the following
      values are in micromol/[min. g dry weight]: basal, 1.19+/-0.13; insulin, 3.89+/
      0.36; epinephrine, 3.46+/-0.27; alpha-stimulation, 4.08+/-0.40; and beta
      stimulation, 3.72+/-0.34). Wortmannin completely inhibited insulin-stimulated and
      selective alpha-stimulated glucose uptake, but it did not affect the epinephrine
      stimulated or selective beta-stimulated glucose uptake. Sequential addition of
      insulin and epinephrine or insulin and alpha-selective stimulation showed
      additive effects on glucose uptake in both cases. Wortmannin further blocked the
      effects of insulin on glycogen synthesis. We conclude that alpha-adrenergic
      stimulation mediates glucose uptake in rat heart through a PI3-K-dependent
      pathway. However, the additive effects of alpha-adrenergic stimulation and
      insulin suggest 2 different isoforms of PI3-K, compartmentation of PI3-K,
      potentiation, or inhibition by wortmannin of another intermediate of the alpha
      adrenergic signaling cascade. The stimulating effects of both the alpha- and the
      beta-adrenergic pathways on glucose uptake are independent of changes in cardiac
      performance.

PMID- 10066683
TI  - Altered crossbridge kinetics in the alphaMHC403/+ mouse model of familial
      hypertrophic cardiomyopathy.
AB  - A mutation in the cardiac beta-myosin heavy chain, Arg403Gln (R403Q), causes a
      severe form of familial hypertrophic cardiomyopathy (FHC) in humans. We used
      small-amplitude (0.25%) length-perturbation analysis to examine the mechanical
      properties of skinned left ventricular papillary muscle strips from mouse hearts
      bearing the R403Q mutation in the alpha-myosin heavy chain (alphaMHC403/+).
      Myofibrillar disarray with variable penetrance occurred in the left ventricular
      free wall of the alphaMHC403/+ hearts. In resting strips (pCa 8), dynamic
      stiffness was approximately 40% greater than in wild-type strips, consistent with
      elevated diastolic stiffness reported for murine hearts with FHC. At pCa 6
      (submaximal activation), strip isometric tension was approximately 3 times higher
      than for wild-type strips, whereas at pCa 5 (maximal activation), tension was
      marginally lower. At submaximal calcium activation the characteristic frequencies
      of the work-producing (b) and work-absorbing (c) steps of the crossbridge were
      less in alphaMHC403/+ strips than in wild-type strips (b=11+/-1 versus 15+/-1 Hz;
      c= 58+/-3 versus 66+/-3 Hz; 27 degrees C). At maximal calcium activation, strip
      oscillatory power was reduced (0. 53+/-0.25 versus 1.03+/-0.18 mW/mm3; 27 degrees
      C), which is partly attributable to the reduced frequency b, at which crossbridge
      work is maximum. The results are consistent with the hypothesis that the R403Q
      mutation reduces the strong binding affinity of myosin for actin. Myosin heads
      may accumulate in a preforce state that promotes cooperative activation of the
      thin filament at submaximal calcium but blunts maximal tension and oscillatory
      power output at maximal calcium. The calcium-dependent effect of the mutation
      (whether facilitating or debilitating), together with a variable degree of
      fibrosis and myofibrillar disorder, may contribute to the diversity of clinical
      symptoms observed in murine FHC.

PMID- 10066684
TI  - Endothelium-derived hyperpolarizing factors and vascular cytochrome P450
      metabolites of arachidonic acid in the regulation of tone.

PMID- 10066685
TI  - An overview of phrenic nerve and diaphragm muscle development in the perinatal
      rat.
AB  - In this overview, we outline what is known regarding the key developmental stages
      of phrenic nerve and diaphragm formation in perinatal rats. These developmental
      events include the following. Cervical axons emerge from the spinal cord during
      embryonic (E) day 11. At approximately E12.5, phrenic and brachial axons from the
      cervical segments merge at the brachial plexi. Subsequently, the two populations
      diverge as phrenic axons continue to grow ventrally toward the diaphragmatic
      primordium and brachial axons turn laterally to grow into the limb bud. A few
      pioneer axons extend ahead of the majority of the phrenic axonal population and
      migrate along a well-defined track toward the primordial diaphragm, which they
      reach by E13.5. The primordial diaphragmatic muscle arises from the
      pleuroperitoneal fold, a triangular protrusion of the body wall composed of the
      fusion of the primordial pleuroperitoneal and pleuropericardial tissues. The
      phrenic nerve initiates branching within the diaphragm at approximately E14, when
      myoblasts in the region of contact with the phrenic nerve begin to fuse and form
      distinct primary myotubes. As the nerve migrates through the various sectors of
      the diaphragm, myoblasts along the nerve's path begin to fuse and form additional
      myotubes. The phrenic nerve intramuscular branching and concomitant diaphragmatic
      myotube formation continue to progress up until E17, at which time the mature
      pattern of innervation and muscle architecture are approximated. E17 is also the
      time of the commencement of inspiratory drive transmission to phrenic motoneurons
      (PMNs) and the arrival of phrenic afferents to the motoneuron pool. During the
      period spanning from E17 to birth (gestation period of approximately 21 days),
      there is dramatic change in PMN morphology as the dendritic branching is
      rearranged into the rostrocaudal bundling characteristic of mature PMNs. This
      period is also a time of significant changes in PMN passive membrane properties,
      action-potential characteristics, and firing properties.

PMID- 10066686
TI  - "Evidence that neuroepithelial endocrine cells control the spontaneous tone in
      guinea pig tracheal preparations".

PMID- 10066687
TI  - Evidence that neuroepithelial endocrine cells control the spontaneous tone in
      guinea pig tracheal preparations.
AB  - The hypothesis that neuroepithelial endocrine (NEE) cells control spontaneous
      tone in isolated guinea pig tracheal preparations was examined. Epithelium
      denuded preparations were unable to develop a normal oscillating tone in 12%
      oxygen (corresponding to systemic arterial oxygen levels) and, instead, developed
      a strong, smooth tone, similar to the "classic" tone in 94% oxygen. Inhibition of
      the hydrogen peroxide-producing NADPH oxidase in the NEE cells by 20 microM
      diphenyleneiodonium chloride transformed, in intact preparations in 94% oxygen,
      the tone from a strong, smooth type to an oscillating tone of considerably less
      force. Similar experiments in denuded preparations showed no change of tone and
      no oscillations. After pretreatment with the catalase inhibitor 3-amino-1,2, 4
      triazole (1 mM), addition of 2 mM hydrogen peroxide to intact preparations
      displaying the oscillating tone caused a transformation to a strong, smooth type.
      These findings support the hypothesis that the spontaneous tone in this
      preparation is largely controlled by the oxygen-sensing NEE cells. For the first
      time, previous findings on isolated cells can be linked to effects in intact
      tissue preparations. The results also suggest that the regulation by the NEE
      cells involves the release of powerful relaxing and contracting factors from the
      epithelium.

PMID- 10066688
TI  - Stroke volume decline during prolonged exercise is influenced by the increase in
      heart rate.
AB  - This study determined whether the decline in stroke volume (SV) during prolonged
      exercise is related to an increase in heart rate (HR) and/or an increase in
      cutaneous blood flow (CBF). Seven active men cycled for 60 min at approximately
      57% peak O2 uptake in a neutral environment (i.e., 27 degrees C, <40% relative
      humidity). They received a placebo control (CON) or a small oral dose (i.e.,
      approximately 7 mg) of the beta1-adrenoceptor blocker atenolol (BB) at the onset
      of exercise. At 15 min, HR and SV were similar during CON and BB. From 15 to 55
      min during CON, a 13% decline in SV was associated with an 11% increase in HR and
      not with an increase in CBF. CBF increased mainly from 5 to 15 min and remained
      stable from 20 to 60 min of exercise in both treatments. However, from 15 to 55
      min during BB, when the increase in HR was prevented by atenolol, the decline in
      SV was also prevented, despite a normal CBF response (i.e., similar to CON).
      Cardiac output was similar in both treatments and stable throughout the exercise
      bouts. We conclude that during prolonged exercise in a neutral environment the
      decline in SV is related to the increase in HR and is not affected by CBF.

PMID- 10066689
TI  - Heart rate during exercise with leg vascular occlusion in spinal cord-injured
      humans.
AB  - Feed-forward and feedback mechanisms are both important for control of the heart
      rate response to muscular exercise, but their origin and relative importance
      remain inadequately understood. To evaluate whether humoral mechanisms are of
      importance, the heart rate response to electrically induced cycling was studied
      in participants with spinal cord injury (SCI) and compared with that elicited
      during volitional cycling in able-bodied persons (C). During voluntary exercise
      at an oxygen uptake of approximately 1 l/min, heart rate increased from 66 +/- 4
      to 86 +/- 4 (SE) beats/min in seven C, and during electrically induced exercise
      at a similar oxygen uptake in SCI it increased from 73 +/- 3 to 110 +/- 8
      beats/min. In contrast, blood pressure increased only in C (from 88 +/- 3 to 99
      +/- 4 mmHg), confirming that, during exercise, blood pressure control is
      dominated by peripheral neural feedback mechanisms. With vascular occlusion of
      the legs, the exercise-induced increase in heart rate was reduced or even
      eliminated in the electrically stimulated SCI. For C, heart rate tended to be
      lower than during exercise with free circulation to the legs. Release of the cuff
      elevated heart rate only in SCI. These data suggest that humoral feedback is of
      importance for the heart rate response to exercise and especially so when
      influence from the central nervous system and peripheral neural feedback from the
      working muscles are impaired or eliminated during electrically induced exercise
      in individuals with SCI.

PMID- 10066690
TI  - Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic
      rats.
AB  - To examine the role of changes in myocardial metabolism in cardiac dysfunction in
      diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to
      induce diabetes and were treated 2 wk later with the carnitine
      palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8
      mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart
      rate, left ventricular systolic pressure, and positive and negative rate of
      pressure development and an increase in end-diastolic pressure. The sarcolemmal
      Na+-K+-ATPase activity was depressed and was associated with a decrease in
      maximal density of binding sites (Bmax) value for high-affinity sites for
      [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of
      diabetic animals with etomoxir partially reversed the depressed cardiac function
      with the exception of heart rate. The high serum triglyceride and free fatty acid
      levels were reduced, whereas the levels of glucose, insulin, and 3,3',-5-triiodo
      L-thyronine were not affected by etomoxir in diabetic animals. The activity of
      Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal
      protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g
      heart wt) for both low-affinity and high-affinity binding sites in control and
      diabetic animals was increased by etomoxir treatment. Etomoxir treatment also
      increased the depressed left ventricular weight of diabetic rats and appeared to
      increase the density of the sarcolemma and transverse tubular system to normalize
      Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization
      may represent an important signal for improving the depressed cardiac function
      and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose
      utilization.

PMID- 10066691
TI  - Command-related distribution of regional cerebral blood flow during attempted
      handgrip.
AB  - To localize a central nervous feed-forward mechanism involved in cardiovascular
      regulation during exercise, brain activation patterns were measured in eight
      subjects by employing positron emission tomography and oxygen-15-labeled water.
      Scans were performed at rest and during rhythmic handgrip before and after
      axillary blockade with bupivacaine. After the blockade, handgrip strength was
      reduced to 25% (range 0-50%) of control values, whereas handgrip-induced heart
      rate and blood pressure increases were unaffected (13 +/- 3 beats/min and 12 +/-
      5 mmHg, respectively; means +/- SE). Before regional anesthesia, handgrip caused
      increased activation in the contralateral sensory motor area, the supplementary
      motor area, and the ipsilateral cerebellum. We found no evidence for changes in
      the activation pattern due to an interaction between handgrip and regional
      anesthesia. This was true for both the blocked and unblocked arm. It remains
      unclear whether the activated areas are responsible for the increase in
      cardiovascular variables, but neural feedback from the contracting muscles was
      not necessary for the activation in the mentioned areas during rhythmic handgrip.

PMID- 10066692
TI  - Pulmonary capillary perfusion: intra-alveolar fractal patterns and interalveolar
      independence.
AB  - Pulmonary capillary perfusion was analyzed from videomicroscopic recordings to
      determine flow switching characteristics among capillary segments in isolated,
      blood-perfused canine lungs. Within each alveolus, the rapid switching pattern
      was repetitive and was, therefore, nonrandom (fractal dimensions near 1.0). This
      self-similarity over time was unexpected in a network widely considered to be
      passive. Among adjacent alveoli, the relationship among the switching patterns
      was even more surprising, for there was virtually no relationship between the
      perfusion patterns (coefficients of determination approaching zero). These
      findings demonstrated that the perfusion patterns in individual alveolar walls
      were independent of their next-door neighbors. The lack of dependence among
      neighboring networks suggests an interesting characteristic: the failure of one
      alveolar-capillary bed would leave its neighbors relatively unaffected, a feature
      of a robust design.

PMID- 10066693
TI  - Lactate kinetics at rest and during exercise in lambs with aortopulmonary shunts.
AB  - In a previous study [G. C. M. Beaufort-Krol, J. Takens, M. C. Molenkamp, G. B.
      Smid, J. J. Meuzelaar, W. G. Zijlstra, and J. R. G. Kuipers. Am. J. Physiol. 275
      (Heart Circ. Physiol. 44): H1503-H1512, 1998], a lower systemic O2 supply was
      found in lambs with aortopulmonary left-to-right shunts. To determine whether the
      lower systemic O2 supply results in increased anaerobic metabolism, we used [1
      13C]lactate to investigate lactate kinetics in eight 7-wk-old lambs with shunts
      and eight control lambs, at rest and during moderate exercise [treadmill; 50% of
      peak O2 consumption (VO2)]. The mean left-to-right shunt fraction in the shunt
      lambs was 55 +/- 3% of pulmonary blood flow. Arterial lactate concentrations and
      the rate of appearance (Ra) and disappearance (Rd) of lactate were similar in
      shunt and control lambs, both at rest (lactate: 1, 201 +/- 76 vs. 1,214 +/- 151
      micromol/l; Ra = Rd: 12.97 +/- 1.71 vs. 12.55 +/- 1.25 micromol. min-1. kg-1) and
      during a similar relative workload. We found a positive correlation between Ra
      and systemic blood flow, O2 supply, and VO2 in both groups of lambs. In
      conclusion, shunt lambs have similar lactate kinetics as do control lambs, both
      at rest and during moderate exercise at a similar fraction of their peak VO2,
      despite a lower systemic O2 supply.

PMID- 10066694
TI  - Shortening of muscle relaxation time after creatine loading.
AB  - The effect of creatine (Cr) supplementation on muscle isometric torque generation
      and relaxation was investigated in healthy male volunteers. Maximal torque
      (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT)
      from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow
      flexions interspersed by 10-s rest intervals. Between the pretest and the
      posttest, subjects ingested Cr monohydrate (4 x 5 g/day; n = 8) or placebo (n =
      8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups.
      Also in the posttest, Tmax and CT were similar between groups. However, posttest
      RT was decreased consistently by approximately 20% (P < 0.05) in the Cr group
      from the first to the last of the 12 contractions. In addition, the mean decrease
      in RT after Cr loading was positively correlated with pretest RT (r = 0.82). It
      is concluded that Cr loading facilitates the rate of muscle relaxation during
      brief isometric muscle contractions without affecting torque production.

PMID- 10066695
TI  - Effects of muscle perfusion pressure on fatigue and systemic arterial pressure in
      human subjects.
AB  - The effects of changes in arterial perfusion across the physiological range on
      the fatigue of a working human hand muscle were studied in seven normal subjects.
      With the hand above heart level, subjects made repeated isometric contractions of
      the adductor pollicis muscle at 50% of maximal voluntary contraction in a 6-s on,
      4-s off cycle. To assess fatigue, a maximal isometric twitch was elicited in each
      "off" period by electrical stimulation of the ulnar nerve. The experiment was
      repeated at least 2 days later with the hand at heart level. Five subjects showed
      faster fatigue with the arm elevated, and two subjects showed little difference
      in fatigue for the two conditions. Central blood pressure rose in proportion to
      fatigue for the subjects overall and returned quickly to its initial level
      afterwards. We conclude that human muscle fatigue can be increased by
      physiological reductions in perfusion pressure. Central blood pressure increases
      as the muscle fatigues, a response that may partially offset declining muscle
      performance.

PMID- 10066696
TI  - Hormone-related, muscle-specific changes in protein metabolism and fiber type
      profile after faba bean intake.
AB  - Male growing Wistar rats were fed, over 15 days, isoenergetic (16.72 +/- 0.49 MJ)
      and isoproteic (11%) diets containing either lactalbumin or raw Vicia faba L.
      (Vf) as the sole source of protein. Compared with pair-fed controls (PF), soleus
      muscles of Vf-fed rats showed increased (P < 0.05) synthesis and breakdown rates.
      In addition, the soleus of Vf-fed rats displayed a decrease (P < 0.05) in type I
      and an increase (P < 0.01) in type IIc fibers compared with that of PF animals.
      On the contrary, extensor digitorum longus muscles of both Vf-fed and PF rats
      showed an increase (P < 0.01) in type I and a reduction (P < 0.05) in type IIb
      fibers together with a decrease (P < 0.05) in the cross-sectional area of the
      latter fibers. Vf-fed rats exhibited a significant decrease in serum insulin (P <
      0.05) and thyrotropin (P < 0.01) levels, together with an increase in plasma
      glucagon (P < 0.05) and 3,5,3'-triiodothyronine (P < 0.01) concentrations,
      compared with the PF group. Both Vf-fed and PF rats experienced an increase in
      corticosterone concentrations (P < 0.01 vs. control; P < 0.05 vs. PF). The muscle
      specific changes in both protein metabolism and fiber type composition may partly
      depend on the hormonal changes that were observed after Vf intake.

PMID- 10066697
TI  - Effect of acute normovolemic hemodilution on distribution of blood flow and
      tissue oxygenation in dog skeletal muscle.
AB  - Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood
      transfusion needs during elective surgery. Tissue oxygenation is maintained by
      increased cardiac output and oxygen extraction and, presumably, a more
      homogeneous tissue perfusion. The aim of this study was to investigate blood flow
      distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 +/- 3
      to 20 +/- 1% was performed in 22 splenectomized, anesthetized beagles (17
      analyzed) ventilated with room air. Normovolemia was confirmed by measurement of
      blood volume. Distribution of perfusion within skeletal muscle was determined by
      using radioactive microspheres. Tissue oxygen partial pressure was assessed with
      a polarographic platinum surface electrode. Cardiac index (3.69 +/- 0.79 vs. 4.79
      +/- 0.73 l. min-1. m-2) and muscle perfusion (4.07 +/- 0.44 vs. 5.18 +/- 0.36 ml.
      100 g-1. min-1) were increased at hematocrit of 20%. Oxygen delivery to skeletal
      muscle was reduced to 74% of baseline values (0.64 +/- 0.06 vs. 0.48 +/- 0.03 ml
      O2. 100 g-1. min-1). Nevertheless, tissue PO2 was preserved (27.4 +/- 1.3 vs.
      29.9 +/- 1. 4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was
      reduced after ANH (20.0 +/- 2.2 vs. 13.9 +/- 1.5%). We conclude that a more
      homogeneous distribution of perfusion is one mechanism for the preservation of
      tissue oxygenation after moderate ANH, despite reduced oxygen delivery.

PMID- 10066698
TI  - Mechanism for the posture-specific plasma volume increase after a single intense
      exercise protocol.
AB  - To test the hypothesis that exercise-induced hypervolemia is a posture-dependent
      process, we measured plasma volume, plasma albumin content, and renal function in
      seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense
      (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h
      after exercise. Plasma volume decreased during exercise but returned to control
      levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume
      increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The
      plasma volume expansion in Up was accompanied by an increase in plasma albumin
      content (0.11 +/- 0.04 g/kg; P < 0.05). Plasma albumin content was unchanged in
      Sup. Urine volume and sodium clearance were lower in Up than Sup (P < 0.05) by 5
      h of recovery. These data suggest that increased plasma albumin content
      contributes to the acute phase of exercise-induced hypervolemia. More
      importantly, the mechanism by which exercise influences the distribution of
      albumin between extra- and intravascular stores after exercise is altered by
      posture and is unknown. We speculate that factors associated with postural
      changes (e.g., central venous pressure) modify the increase in plasma albumin
      content and the plasma volume expansion after exercise.

PMID- 10066699
TI  - Breathing responses to small inspiratory threshold loads in humans.
AB  - To investiage the effect of inspiratory threshold load (ITL) on breathing, all
      previous work studied loads that were much greater than would be encountered
      under pathophysiological conditions. We hypothesized that mild ITL from 2.5 to 20
      cmH2O is sufficient to modify control and sensation of breathing. The study was
      performed in healthy subjects. The results demonstrated that with mild ITL 1)
      inspiratory difficulty sensation could be perceived at an ITL of 2.5 cmH2O; 2)
      tidal volume increased without change in breathing frequency, resulting in
      hyperpnea; and 3) although additional time was required for inspiratory pressure
      to attain the threshold before inspiratory flow was initiated, the total
      inspiratory muscle contraction time remained constant. This resulted in
      shortening of the available time for inspiratory flow, so that the tidal volume
      was maintained or increased by significant increase in mean inspiratory flow. On
      the basis of computer simulation, we conclude that the mild ITL is sufficient to
      increase breathing sensation and alter breathing control, presumably aiming at
      maintaining a certain level of ventilation but minimizing the energy consumption
      of the inspiratory muscles.

PMID- 10066700
TI  - Age-related changes in contractile properties of single skeletal fibers from the
      soleus muscle.
AB  - Peak absolute force, specific tension (peak absolute force per cross-sectional
      area), cross-sectional area, maximal unloaded shortening velocity (Vo; determined
      by the slack test), and myosin heavy chain (MHC) isoform compositions were
      determined in 124 single skeletal fibers from the soleus muscle of 12-, 24-, 30-,
      36-, and 37-mo-old Fischer 344 Brown Norway F1 Hybrid rats. All fibers expressed
      the type I MHC isoform. The mean Vo remained unchanged from 12 to 24 mo but did
      decrease significantly from the 24- to 30-mo time period (from 1.71 +/- 0.13 to
      0.85 +/- 0.09 fiber lengths/s). Fiber cross-sectional area remained constant
      until 36 mo of age, at which time there was a 20% decrease from the values at 12
      mo of age (from 5,558 +/- 232 to 4,339 +/- 280 micrometer2). A significant
      decrease in peak absolute force of single fibers occurred between 12 and 24 mo of
      age (from 51 +/- 2 x 10(-5) to 35 +/- 2 x 10(-5) N) and then remained constant
      until 36 mo, when another 43% decrease occurred. Like peak absolute force, the
      specific tension decreased significantly between 12 and 24 mo by 20%, and another
      32% decline was observed at 37 mo. Thus, by 24 mo, there was a dissociation
      between the loss of fiber cross-sectional area and force. The results suggest
      time-specific changes of the contractile properties with aging that are
      independent of each other. Underlying mechanisms responsible for the time
      dependent and contractile property-specific changes are unknown. Age-related
      changes in the molecular dynamics of myosin may be the underlying mechanism for
      altered force production. The presence of more than one beta/slow MHC isoform may
      be the mechanism for the altered Vo with age.

PMID- 10066701
TI  - Efficacy of recombinant human Hb by 31P-NMR during isovolemic total exchange
      transfusion.
AB  - The ability of recombinant human Hb (rHb1.1), which is being developed as an
      oxygen therapeutic, to support metabolism was measured by in vivo 31P-NMR surface
      coil spectroscopy of the rat abdomen in control animals and in animals subjected
      to isovolemic exchange transfusion to hematocrit of <3% with human serum albumin
      or 5 g/dl rHb1.1. No significant changes in metabolite levels were observed in
      control animals for up to 6 h. The albumin-exchange experiments, however,
      resulted in a more than eightfold increase in Pi and a 50% drop in
      phosphocreatine and ATP within 40 min. The tissue pH dropped from 7.4 to 6.8. The
      decrease in high-energy phosphates obeyed Michaelis-Menten kinetics, with a
      Michaelis-Menten constant of 3% as the hematocrit at which a 50% drop in high
      energy phosphates was observed. Exchange transfusion with rHb1.1 resulted in no
      significant drop in high-energy phosphates, no rise in Pi, and no change in
      tissue pH from 7.35 +/- 0.15 for up to 5 h after exchange. By these criteria,
      rHb1.1 at a plasma Hb concentration of approximately 5 g/dl after total exchange
      transfusion was able to sustain energy metabolism of gut tissue at levels
      indistinguishable from control rats with a threefold higher total Hb level in
      erythrocytes.

PMID- 10066702
TI  - The physiological strain index applied to heat-stressed rats.
AB  - A physiological strain index (PSI) based on heart rate (HR) and rectal
      temperature (Tre) was recently suggested to evaluate exercise-heat stress in
      humans. The purpose of this study was to adjust PSI for rats and to evaluate this
      index at different levels of heat acclimation and training. The corrections of HR
      and Tre to modify the index for rats are as follows: PSI = 5 (Tre t - Tre 0).
      (41.5 - Tre 0)-1 + 5 (HRt - HR0). (550 - HR0)-1, where HRt and Tre t are
      simultaneous measurements taken at any time during the exposure and HR0 and Tre 0
      are the initial measurements. The adjusted PSI was applied to five groups (n = 11
      14 per group) of acclimated rats (control and 2, 5, 10, and 30 days) exposed for
      70 min to a hot climate [40 degrees C, 20% relative humidity (RH)]. A separate
      database representing two groups of acclimated or trained rats was also used and
      involved 20 min of low-intensity exercise (O2 consumption approximately 50 ml.
      min-1. kg-1) at three different climates: normothermic (24 degrees C, 40% RH),
      hot-wet (35 degrees C, 70% RH), and hot-dry (40 degrees C, 20% RH). In
      normothermia, rats also performed moderate exercise (O2 consumption approximately
      60 ml. min-1. kg-1). The adjusted PSI differentiated among acclimation levels and
      significantly discriminated among all exposures during low-intensity exercise (P
      < 0.05). Furthermore, this index was able to assess the individual roles played
      by heat acclimation and exercise training.

PMID- 10066703
TI  - Effect of ambient temperature on human skeletal muscle metabolism during
      fatiguing submaximal exercise.
AB  - To examine the effect of ambient temperature on metabolism during fatiguing
      submaximal exercise, eight men cycled to exhaustion at a workload requiring 70%
      peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart.
      These trials were conducted in ambient temperatures of 3 degrees C (CT), 20
      degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or
      rectal temperature were observed before exercise, both muscle and rectal
      temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT.
      Exercise time was longer in CT compared with NT, which, in turn, was longer
      compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P <
      0.05). Plasma epinephrine concentration was not different at rest or at the point
      of fatigue when the three trials were compared, but concentrations of this
      hormone were higher (P < 0.05) when HT was compared with NT, which in turn was
      higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen
      concentration was not different at rest when the three trials were compared but
      was higher at fatigue in HT compared with NT and CT, which were not different
      (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P <
      0.01). Intramuscular lactate concentration was not different at rest when the
      three trials were compared but was higher (P < 0.05) at fatigue in HT compared
      with CT. No differences in the concentration of the total intramuscular adenine
      nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed
      before or after exercise when the trials were compared. Although intramuscular
      IMP concentrations were not statistically different before or after exercise when
      the three trials were compared, there was an exercise-induced increase (P < 0.01)
      in IMP. These results demonstrate that fatigue during prolonged exercise in hot
      conditions is not related to carbohydrate availability. Furthermore, the
      increased endurance in CT compared with NT is probably due to a reduced
      glycogenolytic rate.

PMID- 10066704
TI  - Resistance training affects GLUT-4 content in skeletal muscle of humans after 19
      days of head-down bed rest.
AB  - This study assessed the effects of inactivity on GLUT-4 content of human skeletal
      muscle and evaluated resistance training as a countermeasure to inactivity
      related changes in GLUT-4 content in skeletal muscle. Nine young men participated
      in the study. For 19 days, four control subjects remained in a -6 degrees head
      down tilt at all times throughout bed rest, except for showering every other day.
      Five training group subjects also remained at bed rest, except during resistance
      training once in the morning. The resistance training consisted of 30 isometric
      maximal voluntary contractions for 3 s each; leg-press exercise was used to
      recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were
      allowed between bouts of maximal contraction. Muscle biopsy samples were obtained
      from the lateral aspect of vastus lateralis (VL) muscle before and after the bed
      rest. GLUT-4 content in VL muscle of the control group was significantly
      decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram
      membrane protein-1, before and after bed rest, respectively), whereas GLUT-4
      significantly increased in the training group with bed rest (510 +/- 158 vs. 663
      +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest,
      respectively). The present study demonstrated that GLUT-4 in VL muscle decreased
      by approximately 16% after 19 days of bed rest, and isometric resistance training
      during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.

PMID- 10066705
TI  - African runners exhibit greater fatigue resistance, lower lactate accumulation,
      and higher oxidative enzyme activity.
AB  - Nine African and eight Caucasian 10-km runners resident at sea level volunteered.
      Maximal O2 consumption and peak treadmill velocity (PTV) were measured by using a
      progressive test, and fatigue resistance [time to fatigue (TTF)] was measured by
      using a newly developed high-intensity running test: 5 min at 72, 80, and 88% of
      individual PTV followed by 92% PTV to exhaustion. Skeletal muscle enzyme
      activities were determined in 12 runners and 12 sedentary control subjects. In a
      comparison of African and Caucasian runners, mean 10-km race time, maximal O2
      consumption, and PTV were similar. In African runners, TTF was 21% longer (P <
      0.01), plasma lactate accumulation after 5 min at 88% PTV was 38% lower (P <
      0.05), and citrate synthase activity was 50% higher (27.9 +/- 7.5 vs. 18.6 +/-
      2.1 micromol. g wet wt-1. min-1, P = 0.02). Africans accumulated lactate at a
      slower rate with increasing exercise intensity (P < 0.05). Among the entire group
      of runners, a higher citrate synthase activity was associated with a longer TTF
      (r = 0.70, P < 0.05), a lower plasma lactate accumulation (r = -0.73, P = 0.01),
      and a lower respiratory exchange ratio (r = -0.63, P < 0.05). We conclude that
      the African and Caucasian runners in the present study differed with respect to
      oxidative enzyme activity, rate of lactate accumulation, and their ability to
      sustain high-intensity endurance exercise.

PMID- 10066706
TI  - Hindlimb immobilization applied to 21-day-old mdx mice prevents the occurrence of
      muscle degeneration.
AB  - Dystrophin-deficient skeletal muscles of mdx mice undergo their first rounds of
      degeneration-regeneration at the age of 14-28 days. This feature is thought to
      result from an increase in motor activity at weaning. In this study, we
      hypothesize that if the muscle is prevented from contracting, it will avoid the
      degenerative changes that normally occur. For this purpose, we developed a
      procedure of mechanical hindlimb immobilization in 3-wk-old mice to restrain
      soleus (Sol) and extensor digitorum longus (EDL) muscles in the stretched or
      shortened position. After a 14-day period of immobilization, the striking feature
      was the low percentage of regenerated (centronucleated) myofibers in Sol and EDL
      muscles, regardless of the length at which they were fixed, compared with those
      on the contralateral side (stretched Sol: 8.4 +/- 6.5 vs. 46.6 +/- 10.3%, P =
      0.0008; shortened Sol: 1.2 +/- 1.6 vs. 50.4 +/- 16.4%, P = 0.0008; stretched EDL:
      05 +/- 0.5 vs. 32.9 +/- 17.5%, P = 0. 002; shortened EDL: 3.3 +/- 3.1 vs. 34.7 +/
      11.1%, P = 0.002). Total numbers of myofibers did not change with
      immobilization. This study shows that limb immobilization prevents the occurrence
      of the first round of myofiber necrosis in mdx mice and suggests that muscle
      contractions play a role in the skeletal muscle degeneration of dystrophin
      deficient mdx mouse muscles.

PMID- 10066707
TI  - Compliance and stability of the bronchial wall in a model of allergen-induced
      lung inflammation.
AB  - Airway wall remodeling in response to inflammation might alter load on airway
      smooth muscle and/or change airway wall stability. We therefore determined airway
      wall compliance and closing pressures in an animal model. Weanling pigs were
      sensitized to ovalbumin (OVA; ip and sc, n = 6) and were subsequently challenged
      three times with OVA aerosol. Control pigs received 0.9% NaCl (n = 4) in place of
      OVA aerosol. Bronchoconstriction in vivo was assessed from lung resistance and
      dynamic compliance. Semistatic airway compliance was recorded ex vivo in isolated
      segments of bronchus, after the final OVA aerosol or 0.9% NaCl challenge.
      Internally or externally applied pressure needed to close bronchial segments was
      determined in the absence or presence of carbachol (1 microM). Sensitized pig
      lungs exhibited immediate bronchoconstriction to OVA aerosol and also
      peribronchial accumulations of monocytes and granulocytes. Compliance was reduced
      in sensitized bronchi in vitro (P < 0.01), and closing pressures were increased
      (P < 0.05). In the presence of carbachol, closing pressures of control and
      sensitized bronchi were not different. We conclude that sensitization and/or
      inflammation increases airway load and airway stability.

PMID- 10066708
TI  - Intestinal reperfusion injury is mediated by IgM and complement.
AB  - Intestinal ischemia-reperfusion injury is dependent on complement. This study
      examines the role of the alternative and classic pathways of complement and IgM
      in a murine model of intestinal ischemia-reperfusion. Wild-type animals, mice
      deficient in complement factor 4 (C4), C3, or Ig, or wild-type mice treated with
      soluble complement receptor 1 were subjected to 40 min of jejunal ischemia and 3
      h of reperfusion. Compared with wild types, knockout and treated mice had
      significantly reduced intestinal injury, indicated by lowered permeability to
      radiolabeled albumin. When animals deficient in Ig were reconstituted with IgM,
      the degree of injury was restored to wild-type levels. Immunohistological
      staining of intestine for C3 and IgM showed colocalization in the mucosa of wild
      type controls and minimal staining for both in the intestine of Ig-deficient and
      C4-deficient mice. We conclude that intestinal ischemia-reperfusion injury is
      dependent on the classic complement pathway and IgM.

PMID- 10066709
TI  - Effects of impaired Ca2+ homeostasis on contraction in postinfarction myocytes.
AB  - The significance of altered Ca2+ influx and efflux pathways on contractile
      abnormalities of myocytes isolated from rat hearts 3 wk after myocardial
      infarction (MI) was investigated by varying extracellular Ca2+ concentration
      ([Ca2+]o, 0.6-5.0 mM) and pacing frequency (0.1-5.0 Hz). Myocytes isolated from 3
      wk MI hearts were significantly longer than those from sham-treated (Sham) hearts
      (125 +/- 1 vs. 114 +/- 1 micrometer, P < 0.0001). At high [Ca2+]o and low pacing
      frequency, conditions that preferentially favored Ca2+ influx over efflux, Sham
      myocytes shortened to a greater extent than 3-wk MI myocytes. Conversely, under
      conditions that favored Ca2+ efflux (low [Ca2+]o and high pacing frequency), MI
      myocytes shortened more than Sham myocytes. At intermediate [Ca2+]o and pacing
      frequencies, differences in steady-state contraction amplitudes between Sham and
      MI myocytes were no longer significant. Collectively, the interpretation of these
      data was that Ca2+ influx and efflux pathways were subnormal in MI myocytes and
      that they contributed to abnormal cellular contractile behavior. Because Na+/Ca2+
      exchange activity, but not whole cell Ca2+ current, was depressed in 3-wk MI rat
      myocytes, our results on steady-state contraction are consistent with, but not
      proof of, the hypothesis that depressed Na+/Ca2+ exchange accounted for abnormal
      contractility in MI myocytes. The effects of depressed Na+/Ca2+ exchange on MI
      myocyte mechanical activity were further evaluated in relaxation from caffeine
      induced contractures. Because Ca2+ uptake by sarcoplasmic reticulum was inhibited
      by caffeine and with the assumption that intracellular Na+ and membrane potential
      were similar between Sham and MI myocytes, myocyte relaxation from caffeine
      induced contracture can be taken as an estimate of Ca2+ extrusion by Na+/Ca2+
      exchange. In MI myocytes, in which Na+/Ca2+ exchange activity was depressed, the
      half time of relaxation (1.54 +/- 0.14 s) was significantly (P < 0.02) prolonged
      compared with that measured in Sham myocytes (1.10 +/- 0.10 s).

PMID- 10066710
TI  - Capsaicin-sensitive C-fiber-mediated protective responses in ozone inhalation in
      rats.
AB  - To assess the role of lung sensory C fibers during and after inhalation of 1
      part/million ozone for 8 h, we compared breathing pattern responses and
      epithelial injury-inflammation-repair in rats depleted of C fibers by systemic
      administration of capsaicin as neonates and in vehicle-treated control animals.
      Capsaicin-treated rats did not develop ozone-induced rapid, shallow breathing.
      Capsaicin-treated rats showed more severe necrosis in the nasal cavity and
      greater inflammation throughout the respiratory tract than did control rats
      exposed to ozone. Incorporation of 5-bromo-2'-deoxyuridine (a marker of DNA
      synthesis associated with proliferation) into terminal bronchiolar epithelial
      cells was not significantly affected by capsaicin treatment in rats exposed to
      ozone. However, when normalized to the degree of epithelial necrosis present in
      each rat studied, there was less 5-bromo-2'-deoxyuridine labeling in the terminal
      bronchioles of capsaicin-treated rats. These observations suggest that the ozone
      induced release of neuropeptides does not measurably contribute to airway
      inflammation but may play a role in modulating basal and reparative airway
      epithelial cell proliferation.

PMID- 10066711
TI  - Modulation of temperature-induced tone by vasoconstrictor agents.
AB  - One of the primary cardiovascular adjustments to hyperthermia is a
      sympathetically mediated increase in vascular resistance in the viscera.
      Nonneural factors such as a change in vascular tone or reactivity may also
      contribute to this response. Therefore, the aim of this study was to determine
      whether vascular smooth muscle tone is altered during heating to physiologically
      relevant temperatures >37 degrees C. Gradually increasing bath temperature from
      37 degrees C (normothermia) to 43 degrees C (severe hyperthermia) produced graded
      contractions in vascular ring segments from rat mesenteric arteries and thoracic
      aortae. In untreated rings these contractions were relatively small, whereas
      hyperthermia elicited near-maximal increases in tension when rings were
      constricted with phenylephrine or KCl before heating. In phenylephrine-treated
      mesenteric arterial rings, the contractile responses to heating were markedly
      attenuated by the Ca2+ channel antagonists nifedipine and diltiazem. Diltiazem
      also blocked the contractile responses to heating in thoracic aortic rings. These
      results demonstrate that hyperthermia has a limited effect on tension generation
      in rat vascular smooth muscle in the absence of vascular tone. However, in the
      presence of agonist-induced tone, tension generation during heating is markedly
      enhanced and dependent on extracellular Ca2+. In conclusion, these data suggest
      that local regulation of vascular tone can contribute to the hemodynamic
      adjustments to hyperthermia.

PMID- 10066712
TI  - Expression of the cell adhesion molecules on leukocytes that demarginate during
      acute maximal exercise.
AB  - The pulmonary vascular bed is an important reservoir for the marginated pool of
      leukocytes that can be mobilized by exercise or catecholamines. This study was
      designed to determine the phenotypic characteristics of leukocytes that are
      mobilized into the circulation during exercise. Twenty healthy volunteers
      performed incremental exercise to exhaustion [maximal O2 consumption (VO2 max)]
      on a cycle ergometer. Blood was collected at baseline, at 3-min intervals during
      exercise, at VO2 max, and 30 min after exercise. Total white cell,
      polymorphonuclear leukocyte (PMN), and lymphocyte counts increased with exercise
      to VO2 max (P < 0.05). Flow cytometric analysis showed that the mean fluorescence
      intensity of L-selectin on PMN (from 14.9 +/- 1 at baseline to 9.5 +/- 1.6 at VO2
      max, P < 0.05) and lymphocytes (from 11.7 +/- 1.2 at baseline to 8 +/- 0.8 at VO2
      max, P < 0.05) decreased with exercise. Mean fluorescence intensity of CD11b on
      PMN increased with exercise (from 10.2 +/- 0.6 at baseline to 25 +/- 2.5 at VO2
      max, P < 0.002) but remained unchanged on lymphocytes. Myeloperoxidase levels in
      PMN did not change with exercise. In vitro studies showed that neither
      catecholamines nor plasma collected at VO2 max during exercise changed leukocyte
      L-selectin or CD11b levels. We conclude that PMN released from the marginated
      pool during exercise express low levels of L-selectin and high levels of CD11b.

PMID- 10066713
TI  - Acinar flow irreversibility caused by perturbations in reversible alveolar wall
      motion.
AB  - Mixing associated with "stretch-and-fold" convective flow patterns has recently
      been demonstrated to play a potentially important role in aerosol transport and
      deposition deep in the lung (J. P. Butler and A. Tsuda. J. Appl. Physiol. 83: 800
      809, 1997), but the origin of this potent mechanism is not well characterized. In
      this study we hypothesized that even a small degree of asynchrony in otherwise
      reversible alveolar wall motion is sufficient to cause flow irreversibility and
      stretch-and-fold convective mixing. We tested this hypothesis using a large-scale
      acinar model consisting of a T-shaped junction of three short, straight, square
      ducts. The model was filled with silicone oil, and alveolar wall motion was
      simulated by pistons in two of the ducts. The pistons were driven to generate a
      low-Reynolds-number cyclic flow with a small amount of asynchrony in boundary
      motion adjusted to match the degree of geometric (as distinguished from pressure
      volume) hysteresis found in rabbit lungs (H. Miki, J. P. Butler, R. A. Rogers,
      and J. Lehr. J. Appl. Physiol. 75: 1630-1636, 1993). Tracer dye was introduced
      into the system, and its motion was monitored. The results showed that even a
      slight asynchrony in boundary motion leads to flow irreversibility with
      complicated swirling tracer patterns. Importantly, the kinematic irreversibility
      resulted in stretching of the tracer with narrowing of the separation between
      adjacent tracer lines, and when the cycle-by-cycle narrowing of lateral distance
      reached the slowly growing diffusion distance of the tracer, mixing abruptly took
      place. This coupling of evolving convective flow patterns with diffusion is the
      essence of the stretch-and-fold mechanism. We conclude that even a small degree
      of boundary asynchrony can give rise to stretch-and-fold convective mixing,
      thereby leading to transport and deposition of fine and ultrafine aerosol
      particles deep in the lung.

PMID- 10066714
TI  - Alterations in diaphragm contractility after nandrolone administration: an
      analysis of potential mechanisms.
AB  - The aim of this study was to evaluate the potential mechanisms underlying the
      improved contractility of the diaphragm (Dia) in adult intact male hamsters after
      nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled
      release capsule (initial dose: 4.5 mg. kg-1. day-1; with weight gain, final dose:
      2.7 mg. kg-1. day-1). Control (Ctl) animals received blank capsules. Isometric
      contractile properties of the Dia were determined in vitro after 4 wk. The
      maximum velocity of unloaded shortening (Vo) was determined in vitro by means of
      the slack test. Dia fibers were classified histochemically on the basis of
      myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the
      relative interstitial space was quantitated. Ca2+-activated myosin ATPase
      activity was determined by quantitative histochemistry in individual diaphragm
      fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically,
      and their proportions were determined by using scanning densitometry. Peak twitch
      and tetanic forces, as well as Vo, were significantly greater in Nan animals
      compared with Ctl. The proportion of type IIa Dia fibers was significantly
      increased in Nan animals. Nan increased the CSA of all fiber types (26-47%),
      whereas the relative interstitial space decreased. The relative contribution of
      fiber types to total costal Dia area was preserved between the groups.
      Proportions of MHC isoforms were similar between the groups. There was a tendency
      for increased expression of MHC2B with Nan. Ca2+-activated myosin ATPase activity
      was increased 35-39% in all fiber types in Nan animals. We conclude that, after
      Nan administration, the increase in Dia specific force results from the
      relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the
      increased ATPase activity promotes a higher rate of cross-bridge turnover and
      thus increased Vo. We speculate that Nan in supraphysiological doses have the
      potential to offset or ameliorate conditions associated with enhanced proteolysis
      and disordered protein turnover.

PMID- 10066715
TI  - Effects of isoproterenol on myocardial structure and function in septic rats.
AB  - In this study we sought to determine the effect of sepsis on two sequelae of
      prolonged (24-h) beta-agonist administration, myocardial hypertrophy and
      catecholamine-induced cardiotoxicity. Sprague-Dawley rats were randomized to
      cecal ligation and perforation (CLP) or sham study groups and then further
      randomized to receive isoproterenol (2.4 mg. kg-1. day-1 iv) or placebo
      treatment. At 24 h, myocardial function was assessed by using the Langendorff
      isolated-heart technique or the heart processed for plain light microscopy. We
      found that 1) sepsis reduced contractile function, indicated by a rightward shift
      in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002);
      2) sepsis-induced myocardial depression was reversed by isoproterenol treatment
      (isoproterenol effect, P < 0.0001); 3) sepsis reduced, but did not block,
      isoproterenol-induced myocardial hypertrophy (isoproterenol effect, P < 0.0001);
      4) sepsis did not protect the heart from catecholamine-induced tissue injury; 5)
      the septic heart was protected against the effects of ischemiareperfusion
      (decreased postreperfusion resting tension, ANOVA with repeated measures, P <
      0.01), an effect attenuated by isoproterenol treatment (P < 0.005); and 6) sepsis
      reduced the incidence of sustained asystole or ventricular fibrillation after
      ischemia-reperfusion (P < 0.05), an effect also attenuated by isoproterenol
      treatment (P < 0.01). We conclude that, in sepsis, beta-agonists induce changes
      in myocardial weight and function consistent with acute myocardial hypertrophy.
      These changes occur at the expense of significant tissue injury and increased
      sensitivity to ischemia-reperfusion-induced tissue injury.

PMID- 10066716
TI  - Exercise-induced alterations in skeletal muscle myosin heavy chain phenotype:
      dose-response relationship.
AB  - This study investigated the effects of exercise training duration on the myosin
      heavy chain (MHC) isoform distribution in rat locomotor muscles. Female Sprague
      Dawley rats (120 days old) were assigned to either a sedentary control group or
      to one of three endurance exercise training groups. Trained animals ran on a
      treadmill at approximately 75% maximal O2 uptake for 10 wk (4-5 days/wk) at one
      of three different exercise durations (30, 60, or 90 min/day). Training resulted
      in increases (P < 0.05) in citrate synthase activity in the soleus and extensor
      digitorum longus in both the 60 and 90 min/day duration groups and in the
      plantaris (Pla) in all three exercise groups. All durations of training resulted
      in a reduction (P < 0.05) in the percentage of MHCIIb and an increase (P < 0.05)
      in the percentage of MHCIIa in the Pla. The magnitude of change in the percentage
      of MHCIIb in the Pla increased as a function of the training duration. In the
      extensor digitorum longus, 90 min of daily exercise promoted a decrease (P <
      0.05) in percentage of MHCIIb and increases (P < 0.05) in the percentages of
      MHCI, MHCIIa, and MHCIId/x. Finally, training durations >/=60 min resulted in an
      increase (P < 0.05) in the percentage of MHCI and a concomitant decrease (P <
      0.05) in the percentage of MHCIIa in the soleus. These results demonstrate that
      increasing the training duration elevates the magnitude of the fast-to-slow shift
      in MHC phenotype in rat hindlimb muscles.

PMID- 10066717
TI  - Peptide toxin blockers of voltage-sensitive K+ channels: inotropic effects on
      diaphragm.
AB  - Agents that block many types of K+ channels (e.g., the aminopyridines) have
      substantial inotropic effects in skeletal muscle. Specific blockers of ATP
      sensitive and Ca2+-activated K+ channels, on the other hand, do not, or
      minimally, alter the force of nonfatigued muscle, consistent with a predominant
      role for voltage-gated K+ channels in regulating muscle force. To test this more
      directly, we examined the effects of peptide toxins, which in other tissues
      specifically block voltage-gated K+ channels, on rat diaphragm in vitro. Twitch
      force was increased in response to alpha-, beta-, and gamma-dendrotoxin and
      tityustoxin Kalpha (17 +/- 6, 22 +/- 5, 42 +/- 14, and 13 +/- 5%; P < 0.05, <
      0.01, < 0.05, < 0.05, respectively) but not in response to delta-dendrotoxin or
      BSA (in which toxins were dissolved). Force during 20-Hz stimulation was also
      increased significantly by alpha-, beta-, and gamma-dendrotoxin and tityustoxin
      Kalpha. Among agents, increases in twitch force correlated with the degree to
      which contraction time was prolonged (r = 0.88, P < 0.02). To determine whether
      inotropic effects could be maintained during repeated contractions, muscle strips
      underwent intermittent 20-Hz train stimulation for a duration of 2 min in
      presence or absence of gamma-dendrotoxin. Force was significantly greater with
      than without gamma-dendrotoxin during repetitive stimulation for the first 60 s
      of repetitive contractions. Despite the approximately 55% higher value for
      initial force in the presence vs. absence of gamma-dendrotoxin, the rate at which
      fatigue occurred was not accelerated by the toxin, as assessed by the amount of
      time over which force declined by 25 and 50%. These data suggest that blocking
      voltage-activated K+ channels may be a useful therapeutic strategy for augmenting
      diaphragm force, provided less toxic blockers of these channels can be found.

PMID- 10066718
TI  - Influence of central antitussive drugs on the cough motor pattern.
AB  - The present study was conducted to determine the effects of administration of
      centrally active antitussive drugs on the cough motor pattern. Electromyograms of
      diaphragm and rectus abdominis muscles were recorded in anesthetized,
      spontaneously breathing cats. Cough was produced by mechanical stimulation of the
      intrathoracic trachea. Centrally acting drugs administered included codeine,
      morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral
      artery administration of all drugs reduced cough number (number of coughs per
      stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner.
      Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on
      cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses
      that inhibited cough number by 80-90%. Morphine lengthened CTtot and inhibited
      diaphragm amplitude during cough, but these effects were not dose dependent. Only
      CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs
      primarily suppress cough by inhibition of expiratory motor drive and cough
      number. CTtot and inspiratory motor drive are relatively insensitive to the
      effects of these drugs. CTtot can be controlled independently from cough number.

PMID- 10066719
TI  - The maximum shortening velocity of muscle should be scaled with activation.
AB  - The purpose of this study was to determine whether the maximum shortening
      velocity (Vmax) in Hill's mechanical model (A. V. Hill. Proc. R. Soc. London Ser.
      B. 126: 136-195, 1938) should be scaled with activation, measured as a fraction
      of the maximum isometric force (Fmax). By using the quick-release method, force
      velocity (F-V) relationships of the wrist flexors were gathered at five different
      activation levels (20-100% of maximum at intervals of 20%) from four subjects.
      The F-V data at different activation levels can be fitted remarkably well with
      Hill's characteristic equation. In general, the shortening velocity decreases
      with activation. With the assumption of nonlinear relationships between Hill
      constants and activation level, a scaled Vmax model was developed. When the F-V
      curves for submaximal activation were forced to converge at the Vmax obtained
      with maximum activation (constant Vmax model), there were drastic changes in the
      shape of the curves. The differences in Vmax values generated by the scaled and
      constant Vmax models were statistically significant. These results suggest that,
      when a Hill-type model is used in musculoskeletal modeling, the Vmax should be
      scaled with activation.

PMID- 10066720
TI  - Influence of body temperature on the development of fatigue during prolonged
      exercise in the heat.
AB  - We investigated whether fatigue during prolonged exercise in uncompensable hot
      environments occurred at the same critical level of hyperthermia when the initial
      value and the rate of increase in body temperature are altered. To examine the
      effect of initial body temperature [esophageal temperature (Tes) = 35.9 +/- 0.2,
      37.4 +/- 0. 1, or 38.2 +/- 0.1 (SE) degrees C induced by 30 min of water
      immersion], seven cyclists (maximal O2 uptake = 5.1 +/- 0.1 l/min) performed
      three randomly assigned bouts of cycle ergometer exercise (60% maximal O2 uptake)
      in the heat (40 degrees C) until volitional exhaustion. To determine the
      influence of rate of heat storage (0.10 vs. 0.05 degrees C/min induced by a water
      perfused jacket), four cyclists performed two additional exercise bouts, starting
      with Tes of 37.0 degrees C. Despite different initial temperatures, all subjects
      fatigued at an identical level of hyperthermia (Tes = 40. 1-40.2 degrees C,
      muscle temperature = 40.7-40.9 degrees C, skin temperature = 37.0-37.2 degrees C)
      and cardiovascular strain (heart rate = 196-198 beats/min, cardiac output = 19.9
      20.8 l/min). Time to exhaustion was inversely related to the initial body
      temperature: 63 +/- 3, 46 +/- 3, and 28 +/- 2 min with initial Tes of
      approximately 36, 37, and 38 degrees C, respectively (all P < 0.05). Similarly,
      with different rates of heat storage, all subjects reached exhaustion at similar
      Tes and muscle temperature (40.1-40.3 and 40. 7-40.9 degrees C, respectively),
      but with significantly different skin temperature (38.4 +/- 0.4 vs. 35.6 +/- 0.2
      degrees C during high vs. low rate of heat storage, respectively, P < 0.05). Time
      to exhaustion was significantly shorter at the high than at the lower rate of
      heat storage (31 +/- 4 vs. 56 +/- 11 min, respectively, P < 0.05). Increases in
      heart rate and reductions in stroke volume paralleled the rise in core
      temperature (36-40 degrees C), with skin blood flow plateauing at Tes of
      approximately 38 degrees C. These results demonstrate that high internal body
      temperature per se causes fatigue in trained subjects during prolonged exercise
      in uncompensable hot environments. Furthermore, time to exhaustion in hot
      environments is inversely related to the initial temperature and directly related
      to the rate of heat storage.

PMID- 10066721
TI  - Maturation of gait dynamics: stride-to-stride variability and its temporal
      organization in children.
AB  - In very young children, immature control of posture and gait results in unsteady
      locomotion. In children of approximately 3 yr of age, gait appears relatively
      mature; however, it is unknown whether the dynamics of walking change beyond this
      age. Because stride dynamics depend on neural control, we hypothesized that motor
      control would continue to develop beyond age 3. To test this hypothesis, we
      measured the gait cycle duration on a stride-by-stride basis in 50 healthy 3- to
      14-yr-old children (25 girls). Measurements of stride-to-stride variability were
      significantly larger both in the 3- and 4-yr-old children, compared with the 6-
      and 7-yr-old children, and in the 6- and 7-yr-old children, compared with the 11-
      to 14-yr-old children. Measurements of the temporal organization of gait also
      revealed significant age-dependent changes. The effects of age persisted even
      after adjusting for height. These findings indicate that mature stride dynamics
      may not be completely developed even in healthy 7-yr-old children and that
      different aspects of stride dynamics mature at different ages.

PMID- 10066722
TI  - Evidence of O2 supply-dependent VO2 max in the exercise-trained human quadriceps.
AB  - Maximal O2 delivery and O2 uptake (VO2) per 100 g of active muscle mass are far
      greater during knee extensor (KE) than during cycle exercise: 73 and 60 ml. min
      1. 100 g-1 (2.4 kg of muscle) (R. S. Richardson, D. R. Knight, D. C. Poole, S. S.
      Kurdak, M. C. Hogan, B. Grassi, and P. D. Wagner. Am. J. Physiol. 268 (Heart
      Circ. Physiol. 37): H1453-H1461, 1995) and 28 and 25 ml. min-1. 100 g-1 (7.5 kg
      of muscle) (D. R. Knight, W. Schaffartzik, H. J. Guy, R. Predilleto, M. C. Hogan,
      and P. D. Wagner. J. Appl. Physiol. 75: 2586-2593, 1993), respectively. Although
      this is evidence of muscle O2 supply dependence in itself, it raises the
      following question: With such high O2 delivery in KE, are the quadriceps still O2
      supply dependent at maximal exercise? To answer this question, seven trained
      subjects performed maximum KE exercise in hypoxia [0.12 inspired O2 fraction
      (FIO2)], normoxia (0.21 FIO2), and hyperoxia (1.0 FIO2) in a balanced order. The
      protocol (after warm-up) was a square wave to a previously determined maximum
      work rate followed by incremental stages to ensure that a true maximum was
      achieved under each condition. Direct measures of arterial and venous blood O2
      concentration in combination with a thermodilution blood flow technique allowed
      the determination of O2 delivery and muscle VO2. Maximal O2 delivery increased
      with inspired O2: 1.3 +/- 0.1, 1.6 +/- 0.2, and 1.9 +/- 0.2 l/min at 0.12, 0.21,
      and 1.0 FIO2, respectively (P < 0.05). Maximal work rate was affected by
      variations in inspired O2 (-25 and +14% at 0.12 and 1.0 FIO2, respectively,
      compared with normoxia, P < 0.05) as was maximal VO2 (VO2 max): 1.04 +/- 0.13, 1.
      24 +/- 0.16, and 1.45 +/- 0.19 l/min at 0.12, 0.21, and 1.0 FIO2, respectively (P
      < 0.05). Calculated mean capillary PO2 also varied with FIO2 (28.3 +/- 1.0, 34.8
      +/- 2.0, and 40.7 +/- 1.9 Torr at 0.12, 0.21, and 1.0 FIO2, respectively, P <
      0.05) and was proportionally related to changes in VO2 max, supporting our
      previous finding that a decrease in O2 supply will proportionately decrease
      muscle VO2 max. As even in the isolated quadriceps (where normoxic O2 delivery is
      the highest recorded in humans) an increase in O2 supply by hyperoxia allows the
      achievement of a greater VO2 max, we conclude that, in normoxic conditions of
      isolated KE exercise, KE VO2 max in trained subjects is not limited by
      mitochondrial metabolic rate but, rather, by O2 supply.

PMID- 10066723
TI  - Estimation of rat muscle blood flow by microdialysis probes perfused with
      ethanol, [14C]ethanol, and 3H2O.
AB  - We used the perfused rat hindquarter to evaluate whether the microdialysis
      ethanol technique can be used to qualitatively estimate nutritive skeletal muscle
      blood flow. Four microdialysis probes were inserted in different hindlimb muscles
      in each of 16 rats. Hindquarters were perfused at blood flow rates ranging from 0
      to 21 ml. 100 g-1. min-1. The microdialysis probes were perfused at 2
      microliter/min with perfusate containing ethanol, [14C]ethanol, and 3H2O. Within
      and between experiments outflow-to-inflow ratios (o/i) generally varied inversely
      with blood flow. When a low flow or no flow was maintained in hindquarters, o/i
      ratios first increased with time (for at least 60 min) and then leveled off. The
      long time constant impaired detection of rapid oscillations in blood flow,
      especially at low blood flow rates. Contractions per se apparently decreased o/i
      ratios independent of blood flow. Ethanol and [14C]ethanol o/i ratios did not
      differ. 3H2O o/i paralleled ethanol and [14C]ethanol o/i ratios but it was
      significantly lower. In conclusion, differences in skeletal muscle blood flow can
      be detected by the microdialysis technique. However, the slow changes in o/i, in
      particular at low blood flow rates, limit the usefulness of the technique for
      measuring dynamic changes in blood flow; caution must also be exerted during
      muscle contractions. 3H2O and [14C]ethanol are good alternatives to ethanol in
      the determination of blood flow by microdialysis.

PMID- 10066724
TI  - Barometric pressures on Mt. Everest: new data and physiological significance.
AB  - Barometric pressures (PB) near the summit of Mt. Everest (altitude 8, 848 m) are
      of great physiological interest because the partial pressure of oxygen is very
      near the limit for human survival. Until recently, the only direct measurement on
      the summit was 253 Torr, which was obtained in October 1981, but, despite being
      only one data point, this value has been used by several investigators. Recently,
      two new studies were carried out. In May 1997, another direct measurement on the
      summit was within approximately 1 Torr of 253 Torr, and meteorologic data
      recorded at the same time from weather balloons also agreed closely. In the
      summer of 1998, over 2,000 measurements were transmitted from a barometer placed
      on the South Col (altitude 7,986 m). The mean PB values during May, June, July,
      and August were 284, 285, 286, and 287 Torr, respectively, and there was close
      agreement with the PB-altitude (h) relationship determined from the 1981 data.
      The PB values are well predicted from the equation PB = exp (6.63268 - 0.1112 h -
      0.00149 h2), where h is in kilometers. The conclusion is that on days when the
      mountain is usually climbed, during May and October, the summit pressure is 251
      253 Torr.

PMID- 10066725
TI  - A source of experimental underestimation of aerosol bolus deposition.
AB  - We examined the measurement error in inhaled and exhaled aerosol concentration
      resulting from the bolus delivery system when small volumes of monodisperse
      aerosols are inspired to different lung depths. A laser photometer that
      illuminated approximately 75% of the breathing path cross section recorded low
      inhaled bolus half-widths (42 ml) and negative deposition values for shallow
      bolus inhalation when the inhalation path of a 60-ml aerosol was straight and
      unobstructed. We attributed these results to incomplete mixing of the inhaled
      aerosol bolus over the breathing path cross section, on the basis of simultaneous
      recordings of the photometer with a particle-counter sampling from either the
      center or the edge of the breathing path. Inserting a 90 degrees bend into the
      inhaled bolus path increased the photometer measurement of inhaled bolus half
      width to 57 ml and yielded positive deposition values. Dispersion, which is
      predominantly affected by exhaled bolus half-width, was not significantly altered
      by the 90 degrees bend. We conclude that aerosol bolus-delivery systems should
      ensure adequate mixing of the inhaled bolus to avoid error in measurement of
      bolus deposition.

PMID- 10066726
TI  - LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in
      breath.
AB  - Laser magnetic resonance spectroscopy (LMRS) is a sensitive and isotope-selective
      technique for determining low concentrations of gaseous free radicals with high
      time resolution. We used this technique to analyze the nitric oxide (NO)
      concentration profile while simultaneously measuring the flow and expired volume
      during several single breathing cycles. Eight healthy, nonallergic volunteers
      were investigated. An initial NO peak was found in all breathing cycles before
      the NO concentration dropped to a relatively stable plateau in the late phase of
      expiration. The nasal NO peak was significantly higher than the oral NO peak. The
      nasal NO plateau was always higher than the oral NO plateau. The height of the
      initial nasal and oral NO peak rose with increasing duration of breath hold,
      whereas the late expiratory NO plateau changed only little for either the nasal
      or the oral breathing cycles. Our findings demonstrate, in line with other
      reports using other techniques, that the nose is the primary source for NO within
      the airways.

PMID- 10066727
TI  - Wavelet transform to quantify heart rate variability and to assess its
      instantaneous changes.
AB  - Heart rate variability is a recognized parameter for assessing autonomous nervous
      system activity. Fourier transform, the most commonly used method to analyze
      variability, does not offer an easy assessment of its dynamics because of
      limitations inherent in its stationary hypothesis. Conversely, wavelet transform
      allows analysis of nonstationary signals. We compared the respective yields of
      Fourier and wavelet transforms in analyzing heart rate variability during dynamic
      changes in autonomous nervous system balance induced by atropine and propranolol.
      Fourier and wavelet transforms were applied to sequences of heart rate intervals
      in six subjects receiving increasing doses of atropine and propranolol. At the
      lowest doses of atropine administered, heart rate variability increased, followed
      by a progressive decrease with higher doses. With the first dose of propranolol,
      there was a significant increase in heart rate variability, which progressively
      disappeared after the last dose. Wavelet transform gave significantly better
      quantitative analysis of heart rate variability than did Fourier transform during
      autonomous nervous system adaptations induced by both agents and provided novel
      temporally localized information.

PMID- 10066728
TI  - Physiological variability of fluid-regulation hormones in young women.
AB  - We tested the physiological reliability of plasma renin activity (PRA) and plasma
      concentrations of arginine vasopressin (P[AVP]), aldosterone (P[ALD]), and atrial
      natriuretic peptide (P[ANP]) in the early follicular phase and midluteal phases
      over the course of two menstrual cycles (n = 9 women, ages 25 +/- 1 yr). The
      reliability (Cronbach's alpha >/=0.80) of these hormones within a given phase of
      the cycle was tested 1) at rest, 2) after 2.5 h of dehydrating exercise, and 3)
      during a rehydration period. The mean hormone concentrations were similar within
      both the early follicular and midluteal phase tests; and the mean concentrations
      of P[ALD] and PRA for the three test conditions were significantly greater during
      the midluteal compared with the early follicular phase. Although Cronbach's alpha
      for resting and recovery P[ANP] were high (0.80 and 0.87, respectively), the
      resting and rehydration values for P[AVP], P[ALD], and PRA were variable between
      trials for the follicular (alpha from 0.49 to 0.55) and the luteal phase (alpha
      from 0.25 to 0. 66). Physiological reliability was better after dehydration for
      P[AVP] and PRA but remained low for P[ALD]. Although resting and recovery P[AVP],
      P[ALD], and PRA were not consistent within a given menstrual phase, the
      differences in the concentrations of these hormones between the different
      menstrual phases far exceeded the variability within the phases, indicating that
      the low within-phase reliability does not prevent the detection of menstrual
      phase-related differences in these hormonal variables.

PMID- 10066729
TI  - Protein crystallization on lipid layers and structure determination of the RNA
      polymerase II transcription initiation complex.

PMID- 10066730
TI  - Switch from an aquaporin to a glycerol channel by two amino acids substitution.
AB  - The MIP (major intrinsic protein) proteins constitute a channel family of
      currently 150 members that have been identified in cell membranes of organisms
      ranging from bacteria to man. Among these proteins, two functionally distinct
      subgroups are characterized: aquaporins that allow specific water transfer and
      glycerol channels that are involved in glycerol and small neutral solutes
      transport. Since the flow of small molecules across cell membranes is vital for
      every living organism, the study of such proteins is of particular interest. For
      instance, aquaporins located in kidney cell membranes are responsible for
      reabsorption of 150 liters of water/day in adult human. To understand the
      molecular mechanisms of solute transport specificity, we analyzed mutant
      aquaporins in which highly conserved residues have been substituted by amino
      acids located at the same positions in glycerol channels. Here, we show that
      substitution of a tyrosine and a tryptophan by a proline and a leucine,
      respectively, in the sixth transmembrane helix of an aquaporin leads to a switch
      in the selectivity of the channel, from water to glycerol.

PMID- 10066731
TI  - Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA.
AB  - Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol to
      yield phosphatidic acid. To date, very little is known about the regulation of
      DGK activity. We have previously identified the DGKtheta isotype, which is
      predominantly expressed in brain (Houssa, B., Schaap, D., van der Wal, J., Goto,
      K., Kondo, H., Yamakawa, A., Shibata, M., Takenawa, T., and Van Blitterswijk, W.
      J. (1997) J. Biol. Chem. 272, 10422-10428). We now report that DGKtheta binds
      specifically to activated RhoA in transfected COS cells as well as in
      nontransfected neuronal N1E-115 cells. Binding is abolished by a point mutation
      (Y34N) in the effector loop of RhoA. DGKtheta does not bind to inactive RhoA, nor
      to the other Rho-family GTPases, Rac or Cdc42. Like active RhoA, DGKtheta
      localizes to the plasma membrane. Strikingly, the binding of activated RhoA to
      DGKtheta completely inhibits DGK catalytic activity. Our results suggest that
      DGKtheta is a downstream effector of RhoA and that its activity is negatively
      regulated by RhoA. Through accumulation of newly produced diacylglycerol, RhoA
      mediated inhibition of DGKtheta may lead to enhanced PKC activity in response to
      external stimuli.

PMID- 10066732
TI  - Nitric oxide inhibits caspase-3 by S-nitrosation in vivo.
AB  - In cultured human endothelial cells, physiological levels of NO prevent apoptosis
      and interfere with the activation of the caspase cascade. In vitro data have
      demonstrated that NO inhibits the activity of caspase-3 by S-nitrosation of the
      enzyme. Here we present evidence for the in vivo occurrence and functional
      relevance of this novel antiapoptotic mechanism. To demonstrate that the cysteine
      residue Cys-163 of caspase-3 is S-nitrosated, cells were transfected with the Myc
      tagged p17 subunit of caspase-3. After incubation of the transfected cells with
      different NO donors, Myc-tagged p17 was immunoprecipitated with anti-Myc
      antibody. S-Nitrosothiol was detected in the immunoprecipitate by electron spin
      resonance spectroscopy after liberation and spin trapping of NO by N-methyl-D
      glucamine-dithiocarbamate-iron complex. Transfection of cells with a p17 mutant,
      where the essential Cys-163 was mutated into alanine, completely prevented S
      nitrosation of the enzyme. As a functional correlate, in human umbilical vein
      endothelial cells the NO donors sodium nitroprusside or PAPA NONOate (50 microM)
      significantly reduced the increase in caspase-3-like activity induced by
      overexpressing caspase-3 by 75 and 70%, respectively. When human umbilical vein
      endothelial cells were cotransfected with beta-galactosidase, morphological
      analysis of stained cells revealed that cell death induction by overexpression of
      caspase-3 was completely suppressed in the presence of sodium nitroprusside, PAPA
      NONOate, or S-nitroso-L-cysteine (50 microM). Thus, NO supplied by exogenous NO
      donors serves in vivo as an antiapoptotic regulator of caspase activity via S
      nitrosation of the Cys-163 residue of caspase-3.

PMID- 10066733
TI  - The relationship between the free concentrations of Ca2+ and Ca2+-calmodulin in
      intact cells.
AB  - Using stably expressed fluorescent indicator proteins, we have determined for the
      first time the relationship between the free Ca2+ and Ca2+-calmodulin
      concentrations in intact cells. A similar relationship is obtained when the free
      Ca2+ concentration is externally buffered or when it is transiently increased in
      response to a Ca2+-mobilizing agonist. Below a free Ca2+ concentration of 0.2
      microM, no Ca2+-calmodulin is detectable. A global maximum free Ca2+-calmodulin
      concentration of approximately 45 nM is produced when the free Ca2+ concentration
      exceeds 3 microM, and a half-maximal concentration is produced at a free Ca2+
      concentration of 1 microM. Data for fractional saturation of the indicators
      suggest that the total concentration of calmodulin-binding proteins is
      approximately 2-fold higher than the total calmodulin concentration. We conclude
      that high-affinity calmodulin targets (Kd </= 10 nM) are efficiently activated
      throughout the cell, but efficient activation of low-affinity targets (Kd >/= 100
      nM) occurs only where free Ca2+-calmodulin concentrations can be locally
      enhanced.

PMID- 10066734
TI  - Targeted construction of phosphorylation-independent beta-arrestin mutants with
      constitutive activity in cells.
AB  - Arrestin proteins play a key role in the desensitization of G protein-coupled
      receptors (GPCRs). Recently we proposed a molecular mechanism whereby arrestin
      preferentially binds to the activated and phosphorylated form of its cognate
      GPCR. To test the model, we introduced two different types of mutations into beta
      arrestin that were expected to disrupt two crucial elements that make beta
      arrestin binding to receptors phosphorylation-dependent. We found that two beta
      arrestin mutants (Arg169 --> Glu and Asp383 --> Ter) (Ter, stop codon) are indeed
      "constitutively active." In vitro these mutants bind to the agonist-activated
      beta2-adrenergic receptor (beta2AR) regardless of its phosphorylation status.
      When expressed in Xenopus oocytes these beta-arrestin mutants effectively
      desensitize beta2AR in a phosphorylation-independent manner. Constitutively
      active beta-arrestin mutants also effectively desensitize delta opioid receptor
      (DOR) and restore the agonist-induced desensitization of a truncated DOR lacking
      the critical G protein-coupled receptor kinase (GRK) phosphorylation sites. The
      kinetics of the desensitization induced by phosphorylation-independent mutants in
      the absence of receptor phosphorylation appears identical to that induced by wild
      type beta-arrestin + GRK3. Either of the mutations could have occurred naturally
      and made receptor kinases redundant, raising the question of why a more complex
      two-step mechanism (receptor phosphorylation followed by arrestin binding) is
      universally used.

PMID- 10066735
TI  - RNA determinants for translational editing. Mischarging a minihelix substrate by
      a tRNA synthetase.
AB  - The fidelity of protein synthesis requires efficient discrimination of amino acid
      substrates by aminoacyl-tRNA synthetases. Accurate discrimination of the
      structurally similar amino acids, valine and isoleucine, by isoleucyl-tRNA
      synthetase (IleRS) results, in part, from a hydrolytic editing reaction, which
      prevents misactivated valine from being stably joined to tRNAIle. The editing
      reaction is dependent on the presence of tRNAIle, which contains discrete D-loop
      nucleotides that are necessary to promote editing of misactivated valine. RNA
      minihelices comprised of just the acceptor-TPsiC helix of tRNAIle are substrates
      for specific aminoacylation by IleRS. These substrates lack the aforementioned D
      loop nucleotides. Because minihelices contain determinants for aminoacylation, we
      thought that they might also play a role in editing that has not previously been
      recognized. Here we show that, in contrast to tRNAIle, minihelixIle is unable to
      trigger the hydrolysis of misactivated valine and, in fact, is mischarged with
      valine. In addition, mutations in minihelixIle that enhance or suppress charging
      with isoleucine do the same with valine. Thus, minihelixIle contains signals for
      charging (by IleRS) that are independent of the amino acid and, by itself,
      minihelixIle provides no determinants for editing. An RNA hairpin that mimics the
      D-stem/loop of tRNAIle is also unable to induce the hydrolysis of misactivated
      valine, both by itself and in combination with minihelixIle. Thus, the native
      tertiary fold of tRNAIle is required to promote efficient editing. Considering
      that the minihelix is thought to be the more ancestral part of the tRNA
      structure, these results are consistent with the idea that, during the
      development of the genetic code, RNA determinants for editing were added after
      the establishment of an aminoacylation system.

PMID- 10066736
TI  - Genetic selection of mutations in the high affinity K+ transporter HKT1 that
      define functions of a loop site for reduced Na+ permeability and increased Na+
      tolerance.
AB  - Potassium is an important macronutrient required for plant growth, whereas sodium
      (Na+) can be toxic at high concentrations. The wheat K+ uptake transporter HKT1
      has been shown to function in yeast and oocytes as a high affinity K+-Na+
      cotransporter, and as a low affinity Na+ transporter at high external Na+. A
      previous study showed that point mutations in HKT1, which confer enhancement of
      Na+ tolerance to yeast, can be isolated by genetic selection. Here we report on
      the isolation of mutations in new domains of HKT1 showing further large increases
      in Na+ tolerance. By selection in a Na+ ATPase deletion mutant of yeast that
      shows a high Na+ sensitivity, new HKT1 mutants at positions Gln-270 and Asn-365
      were isolated. Several independent mutations were isolated at the Asn-365 site.
      N365S dramatically increased Na+ tolerance in yeast compared with all other HKT1
      mutants. Cation uptake experiments in yeast and biophysical characterization in
      Xenopus oocytes showed that the mechanisms underlying the Na+ tolerance conferred
      by the N365S mutant were: reduced inhibition of high affinity Rb+ (K+) uptake at
      high Na+ concentrations, reduced low affinity Na+ uptake, and reduced Na+ to K+
      content ratios in yeast. In addition, the N365S mutant could be clearly
      distinguished from less Na+-tolerant HKT1 mutants by a markedly decreased
      relative permeability for Na+ at high Na+ concentrations. The new mutations
      contribute to the identification of new functional domains and an amino acid in a
      loop domain that is involved in cation specificity of a plant high affinity K+
      transporter and will be valuable for molecular analyses of Na+ transport
      mechanisms and stress in plants.

PMID- 10066737
TI  - A chimeric gastric H+,K+-ATPase inhibitable with both ouabain and SCH 28080.
AB  - 2-Methyl-8-(phenylmethoxy)imidazo(1,2-a)pyridine-3acetonitrile+ ++ (SCH 28080) is
      a K+ site inhibitor specific for gastric H+,K+-ATPase and seems to be a
      counterpart of ouabain for Na+,K+-ATPase from the viewpoint of reaction pattern
      (i.e. reversible binding, K+ antagonism, and binding on the extracellular side).
      In this study, we constructed several chimeric molecules between H+,K+-ATPase and
      Na+,K+-ATPase alpha-subunits by using rabbit H+,K+-ATPase as a parental molecule.
      We found that the entire extracellular loop 1 segment between the first and
      second transmembrane segments (M1 and M2) and the luminal half of the M1
      transmembrane segment of H+, K+-ATPase alpha-subunit were exchangeable with those
      of Na+, K+-ATPase, respectively, preserving H+,K+-ATPase activity, and that these
      segments are not essential for SCH 28080 binding. We found that several amino
      acid residues, including Glu-822, Thr-825, and Pro-829 in the M6 segment of H+,K+
      ATPase alpha-subunit are involved in determining the affinity for this inhibitor.
      Furthermore, we found that a chimeric H+,K+-ATPase acquired ouabain sensitivity
      and maintained SCH 28080 sensitivity when the loop 1 segment and Cys-815 in the
      loop 3 segment of the H+,K+-ATPase alpha-subunit were simultaneously replaced by
      the corresponding segment and amino acid residue (Thr) of Na+,K+-ATPase,
      respectively, indicating that the binding sites of ouabain and SCH 28080 are
      separate. In this H+, K+-ATPase chimera, 12 amino acid residues in M1, M4, and
      loop 1-4 that have been suggested to be involved in ouabain binding of Na+, K+
      ATPase alpha-subunit are present; however, the low ouabain sensitivity indicates
      the possibility that the sensitivity may be increased by additional amino acid
      substitutions, which shift the overall structural integrity of this chimeric
      H+,K+-ATPase toward that of Na+,K+-ATPase.

PMID- 10066738
TI  - Direct evidence that the proton motive force inhibits membrane translocation of
      positively charged residues within membrane proteins.
AB  - The M13 phage procoat protein requires both its signal sequence and its membrane
      anchor sequence in the mature part of the protein for membrane insertion.
      Translocation of its short acidic periplasmic loop is stimulated by the proton
      motive force (pmf) and does not require the Sec components. We now find that the
      pmf becomes increasingly important for the translocation of negatively charged
      residues within procoat when the hydrophobicity of the signal or membrane anchor
      is incrementally reduced. In contrast, we find that the pmf inhibits
      translocation of the periplasmic loop when it contains one or two positively
      charged residues. This inhibitory effect of the pmf is stronger when the
      hydrophobicity of the inserting procoat protein is compromised. No pmf effect is
      observed for translocation of an uncharged periplasmic loop even when the
      hydrophobicity is reduced. We also show that the Delta Psi component of the pmf
      is necessary and sufficient for insertion of representative constructs and that
      the translocation effects of charged residues are primarily due to the DeltaPsi
      component of the pmf and not the pH component.

PMID- 10066739
TI  - Coupling of the oxygen-linked interaction energy for inositol hexakisphosphate
      and bezafibrate binding to human HbA0.
AB  - The energetics of signal propagation between different functional domains (i.e.
      the binding sites for O2, inositol hexakisphospate (IHP), and bezafibrate (BZF))
      of human HbA0 was analyzed at different heme ligation states and through the use
      of a stable, partially heme ligated intermediate. Present data allow three main
      conclusions to be drawn, and namely: (i) IHP and BZF enhance each others binding
      as the oxygenation proceeds, the coupling free energy going from close to zero in
      the deoxy state to -3.4 kJ/mol in the oxygenated form; (ii) the simultaneous
      presence of IHP and BZF stabilizes the hemoglobin T quaternary structure at very
      low O2 pressures, but as oxygenation proceeds it does not impair the transition
      toward the R structure, which indeed occurs also under these conditions; (iii)
      under room air pressure (i.e. pO2 = 150 torr), IHP and BZF together induce the
      formation of an asymmetric dioxygenated hemoglobin tetramer, whose features
      appear reminiscent of those suggested for transition state species (i.e. T- and R
      like tertiary conformation(s) within a quaternary R-like structure).

PMID- 10066740
TI  - Clusterin has chaperone-like activity similar to that of small heat shock
      proteins.
AB  - Clusterin is a highly conserved protein which is expressed at increased levels by
      many cell types in response to a broad variety of stress conditions. A genuine
      physiological function for clusterin has not yet been established. The results
      presented here demonstrate for the first time that clusterin has chaperone-like
      activity. At physiological concentrations, clusterin potently protected
      glutathione S-transferase and catalase from heat-induced precipitation and alpha
      lactalbumin and bovine serum albumin from precipitation induced by reduction with
      dithiothreitol. Enzyme-linked immunosorbent assay data showed that clusterin
      bound preferentially to heat-stressed glutathione S-transferase and to
      dithiothreitol-treated bovine serum albumin and alpha-lactalbumin. Size exclusion
      chromatography and SDS-polyacrylamide gel electrophoresis analyses showed that
      clusterin formed high molecular weight complexes (HMW) with all four proteins
      tested. Small heat shock proteins (sHSP) also act in this way to prevent protein
      precipitation and protect cells from heat and other stresses. The stoichiometric
      subunit molar ratios of clusterin:stressed protein during formation of HMW
      complexes (which for the four proteins tested ranged from 1.0:1.3 to 1.0:11) is
      less than the reported ratios for sHSP-mediated formation of HMW complexes
      (1.0:1.0 or greater), indicating that clusterin is a very efficient chaperone.
      Our results suggest that clusterin may play a sHSP-like role in cytoprotection.

PMID- 10066741
TI  - Molecular characterization of two endogenous double-stranded RNAs in rice and
      their inheritance by interspecific hybrids.
AB  - We completely sequenced 13,936 nucleotides (nt) of a double-stranded RNA (dsRNA)
      of wild rice (W-dsRNA). A single long open reading frame (13,719 nt) containing
      the conserved motifs of RNA-dependent RNA polymerase and RNA helicase was located
      in the coding strand. The identity between entire nucleotide sequence of W-dsRNA
      and that of the dsRNA of temperate japonica rice (J-dsRNA, 13,952 nt) was 75.5%.
      A site-specific discontinuity (nick) was identified at nt 1,197 from the 5' end
      of the coding strand of W-dsRNA. This nick is also located at nt 1,211 from the
      5' end in the coding strand of J-dsRNA. The dsRNA copy number was increased more
      than 10-fold in pollen grains of both rice plants. This remarkable increase may
      be responsible for the highly efficient transmission of J-dsRNA via pollen that
      we already reported. J-dsRNA and W-dsRNA were also efficiently transmitted to
      interspecific F1 hybrids. Seed-mediated dsRNA transmission to F2 plants was also
      highly efficient when the maternal parent was wild rice. The efficiency of dsRNA
      transmission to F2 plants was reduced when the maternal parent was temperate
      japonica rice; however, the reduced rates in F2 plants were returned to high
      levels in F3 plants.

PMID- 10066742
TI  - DnaB from Thermus aquaticus unwinds forked duplex DNA with an asymmetric tail
      length dependence.
AB  - DnaB helicase is a ring-shaped hexamer of 300 kDa that is essential for
      replication of the bacterial chromosome. The dnaB gene from Thermus aquaticus was
      isolated and cloned, and its gene product was expressed and purified to
      homogeneity. A helicase assay was developed, and optimal conditions for T.
      aquaticus DnaB activity were determined using a forked duplex DNA substrate. The
      activity required a hydrolyzable nucleoside triphosphate and both 5'- and 3'
      single-stranded DNA tail regions. Under conditions of single enzymatic turnover,
      the lengths of the 5'- and 3'-single-stranded regions were varied, and 6-10
      nucleotides of the 5'-single-stranded tail and 21-30 nucleotides of the 3'-single
      stranded tail markedly stimulated the unwinding rate. These data suggest that
      DnaB from T. aquaticus interacts with both DNA single-stranded tails during
      unwinding and that a greater portion of the 3'-tail is in contact with the
      protein. Two models are consistent with these data. In one model, the 5'-single
      stranded region passes through the central hole of the DnaB ring, and the 3'-tail
      makes extensive contact with the outside of the protein. In the other model, the
      3'-single-stranded region passes through the DnaB ring, and the outside of the
      protein contacts the 5'-tail.

PMID- 10066743
TI  - Chlamydomonas chloroplast ferrous hemoglobin. Heme pocket structure and reactions
      with ligands.
AB  - We report the optical and resonance Raman spectral characterization of ferrous
      recombinant Chlamydomonas LI637 hemoglobin. We show that it is present in three
      pH-dependent equilibrium forms including a 4-coordinate species at acid pH, a 5
      coordinate high spin species at neutral pH, and a 6-coordinate low spin species
      at alkaline pH. The proximal ligand to the heme is the imidazole group of a
      histidine. Kinetics of the reactions with ligands were determined by stopped-flow
      spectroscopy. At alkaline pH, combination with oxygen, nitric oxide, and carbon
      monoxide displays a kinetic behavior that is interpreted as being rate-limited by
      conversion of the 6-coordinate form to a reactive 5-coordinate form. At neutral
      pH, combination rates of the 5-coordinate form with oxygen and carbon monoxide
      were much faster (>10(7) microM-1 s-1). The dissociation rate constant measured
      for oxygen is among the slowest known, 0.014 s-1, and is independent of pH.
      Replacement of the tyrosine 63 (B10) by leucine or of the putative distal
      glutamine by glycine increases the dissociation rate constant 70- and 30-fold and
      increases the rate of autoxidation 20- and 90-fold, respectively. These results
      are consistent with at least two hydrogen bonds stabilizing the bound oxygen
      molecule, one from tyrosine B10 and the other from the distal glutamine. In
      addition, the high frequency (232 cm-1) of the iron-histidine bond suggests a
      structure that lacks any proximal strain thus contributing to high ligand
      affinity.

PMID- 10066744
TI  - Characterization of the interaction between the herpes simplex virus type I Fc
      receptor and immunoglobulin G.
AB  - Herpes simplex virus type I (HSV-1) virions and HSV-1-infected cells bind to
      human immunoglobulin G (hIgG) via its Fc region. A complex of two surface
      glycoproteins encoded by HSV-1, gE and gI, is responsible for Fc binding. We have
      co-expressed soluble truncated forms of gE and gI in Chinese hamster ovary cells.
      Soluble gE-gI complexes can be purified from transfected cell supernatants using
      a purification scheme that is based upon the Fc receptor function of gE-gI. Using
      gel filtration and analytical ultracentrifugation, we determined that soluble gE
      gI is a heterodimer composed of one molecule of gE and one molecule of gI and
      that gE-gI heterodimers bind hIgG with a 1:1 stoichiometry. Biosensor-based
      studies of the binding of wild type or mutant IgG proteins to soluble gE-gI
      indicate that histidine 435 at the CH2-CH3 domain interface of IgG is a critical
      residue for IgG binding to gE-gI. We observe many similarities between the
      characteristics of IgG binding by gE-gI and by rheumatoid factors and bacterial
      Fc receptors such as Staphylococcus aureus protein A. These observations support
      a model for the origin of some rheumatoid factors, in which they represent anti
      idiotypic antibodies directed against antibodies to bacterial and viral Fc
      receptors.

PMID- 10066745
TI  - Effect of tetrahydropyrimidine derivatives on protein-nucleic acids interaction.
      Type II restriction endonucleases as a model system.
AB  - 2-Methyl-4-carboxy,5-hydroxy-3,4,5,6-tetrahydropyri- midine (THP(A) or
      hydroxyectoine) and 2-methyl,4-carboxy-3,4,5, 6-tetrahydropyrimidine (THP(B) or
      ectoine) are now recognized as ubiquitous bacterial osmoprotectants. To evaluate
      the impact of tetrahydropyrimidine derivatives (THPs) on protein-DNA interaction
      and on restriction-modification systems, we have examined their effect on the
      cleavage of plasmid DNA by 10 type II restriction endonucleases. THP(A)
      completely arrested the cleavage of plasmid and bacteriophage lambda DNA by EcoRI
      endonuclease at 0.4 mM and the oligonucleotide (d(CGCGAATTCGCG))2 at about 4.0
      mM. THP(B) was 10-fold less effective than THP(A), whereas for betaine and
      proline, a notable inhibition was observed only at 100 mM. Similar effects of
      THP(A) were observed for all tested restriction endonucleases, except for SmaI
      and PvuII, which were inhibited only partially at 50 mM THP(A). No effect of
      THP(A) on the activity of DNase I, RNase A, and Taq DNA polymerase was noticed.
      Gel-shift assays showed that THP(A) inhibited the EcoRI-(d(CGCGAATTCGCG))2
      complex formation, whereas facilitated diffusion of EcoRI along the DNA was not
      affected. Methylation of the carboxy group significantly decreased the activity
      of THPs, suggesting that their zwitterionic character is essential for the
      inhibition effect. Possible mechanisms of inhibition, the role of THPs in the
      modulation of the protein-DNA interaction, and the in vivo relevance of the
      observed phenomena are discussed.

PMID- 10066746
TI  - The geranylgeranyltransferase I inhibitor GGTI-298 induces hypophosphorylation of
      retinoblastoma and partner switching of cyclin-dependent kinase inhibitors. A
      potential mechanism for GGTI-298 antitumor activity.
AB  - The geranylgeranyltransferase I inhibitor GGTI-298 has recently been shown to
      arrest human tumor cells in the G1 phase of the cell cycle, induce apoptosis, and
      inhibit tumor growth in nude mice. In the present manuscript, we provide a
      possible mechanism by which GGTI-298 mediates its tumor growth arrest. Treatment
      of the human lung carcinoma cell line Calu-1 with GGTI-298 results in inhibition
      of the phosphorylation of retinoblastoma protein, a critical step for G1/S
      transition. The kinase activities of two G1/S cyclin-dependent kinases, CDK2 and
      CDK4, are inhibited in Calu-1 cells treated with GGTI-298. Furthermore, GGTI-298
      has little effect on the expression levels of CDK2, CDK4, CDK6, cyclins D1 and E,
      but decreases the levels of cyclin A. GGTI-298 increases the levels of the cyclin
      dependent kinase inhibitors p21 and p15 and had little effect on those of p27 and
      p16. Most interesting is the ability of GGTI-298 to induce partner switching for
      several CDK inhibitors. GGTI-298 promotes binding of p21 and p27 to CDK2 while
      decreasing their binding to CDK6. Reversal of partner switching and G1 block was
      observed after removal of GGTI-298. Furthermore, GGTI-298 treatment results in an
      increased binding of p15 to CDK4, which is paralleled with decreased binding to
      p27. The results demonstrate that the GGTI-298-mediated G1 block in Calu-1 cells
      involves increased expression and partner switching of CDK inhibitors resulting
      in inhibition of CDK2 and CDK4, and retinoblastoma protein phosphorylation.

PMID- 10066747
TI  - The matrix metalloproteinase-9 regulates the insulin-like growth factor-triggered
      autocrine response in DU-145 carcinoma cells.
AB  - The androgen-independent human prostate adenocarcinoma cell line DU-145
      proliferates in serum-free medium and produces insulin-like growth factors (IGF)
      I, IGF-II, and the IGF type-1 receptor (IGF-1R). They also secrete three IGF
      binding proteins (IGFBP), IGFBP-2, -3, and -4. Of these, immunoblot analysis
      revealed selective proteolysis of IGFBP-3, yielding fragments of 31 and 19 kDa.
      By using an anti-IGF-I-specific monoclonal antibody (mAb), we detect surface
      receptor-bound IGF-I on serum-starved DU-145 cells, which activates IGF-1R and
      triggers a mitogenic signal. Incubation of DU-145 cells with blocking anti-IGF-I,
      anti-IGF-II, or anti-IGF-I plus anti-IGF-II mAb does not, however, inhibit serum
      free growth of DU-145. Conversely, anti-IGF-1R mAb and IGFBP-3 inhibit DNA
      synthesis. IGFBP-3 also modifies the DU-145 cell cycle, decreases p34(cdc2)
      levels, and IGF-1R autophosphorylation. The antiproliferative IGFBP-3 activity is
      not IGF-independent, since des-(1-3)IGF-I, which does not bind to IGFBP-3,
      reverses its inhibitory effect. DU-145 also secretes the matrix metalloproteinase
      (MMP)-9, which can be detected in both a soluble and a membrane-bound form.
      Matrix metalloproteinase inhibitors, but not serpins, abrogate DNA synthesis in
      DU-145 associated with the blocking of IGFBP-3 proteolysis. Overexpression of an
      antisense cDNA for MMP-9 inhibits 80% of DU-145 cell proliferation that can be
      reversed by IGF-I in a dose-dependent manner. Inhibition of MMP-9 expression is
      also associated with a decrease in IGFBP-3 proteolysis and with reduced signaling
      through the IGF-1R. Our data indicate an IGF autocrine loop operating in DU-145
      cells, specifically modulated by IGFBP-3, whose activity may in turn be regulated
      by IGFBP-3 proteases such as MMP-9.

PMID- 10066748
TI  - Effect of mutations at the monomer-monomer interface of cAMP receptor protein on
      specific DNA binding.
AB  - To determine the thermodynamic role of binding of an operon to cAMP receptor
      protein (CRP) in the activation of transcription, isothermal titration
      calorimetry measurements were performed on the binding of three 40-base pair DNA
      sequences to the cyclic nucleoside complexes of CRP and its mutants at 296 K. The
      three 40-base pair sequences consisted of a consensus DNA (conDNA) duplex derived
      from the CRP-binding site sequences of the operons activated by CRP and two DNA
      sequences based on the CRP-binding site sequences of the lac operon (lacDNA) and
      of the gal operon (galDNA). The mutants of CRP consisted of a T127L mutant, a
      S128A mutant, and a mutant containing both mutations (CRP*) which not only alter
      the transcriptional activity of the CRP complexes but also are involved in the
      monomer-monomer interfacial interactions of the CRP dimer. The binding reactions
      of the DNA duplexes to the fully cNMP-ligated CRP-mutant complexes were
      endothermic with binding constants as high as 6.6 +/- 1.1 x 10(6) M-1
      (conDNA.CRP(cAMP)2). ConDNA binding to the unligated T127L and CRP* mutants was
      observed as well as conDNA and lacDNA binding to CRP with cAMP bound to only one
      monomer. The reduction of the binding constants with increase in KCl
      concentration indicated the formation of two ion pairs for the cAMP-ligated CRP
      and S128A complexes and four ion pairs for the cAMP-ligated T127L and CRP*
      complexes. Reduction of the DNA binding constants upon substitution of D2O for
      H2O in the buffer, the large heat capacity changes, and the enthalpy-entropy
      compensation exhibited by the binding reactions indicate the importance of
      dehydration in the binding reaction. Small angle neutron scattering measurements
      on the lacDNA.CRP(cAMP)2 complex in D2O/H2O mixtures show that the DNA is bent
      around the cAMP-ligated protein in solution.

PMID- 10066749
TI  - High base pair opening rates in tracts of GC base pairs.
AB  - Sequence-dependent structural features of the DNA double helix have a strong
      influence on the base pair opening dynamics. Here we report a detailed study of
      the kinetics of base pair breathing in tracts of GC base pairs in DNA duplexes
      derived from 1H NMR measurements of the imino proton exchange rates upon
      titration with the exchange catalyst ammonia. In the limit of infinite exchange
      catalyst concentration, the exchange times of the guanine imino protons of the GC
      tracts extrapolate to much shorter base pair lifetimes than commonly observed for
      isolated GC base pairs. The base pair lifetimes in the GC tracts are below 5 ms
      for almost all of the base pairs. The unusually rapid base pair opening dynamics
      of GC tracts are in striking contrast to the behavior of AT tracts, where very
      long base pair lifetimes are observed. The implication of these findings for the
      structural principles governing spontaneous helix opening as well as the DNA
      binding specificity of the cytosine-5-methyltransferases, where flipping of the
      cytosine base has been observed, are discussed.

PMID- 10066750
TI  - Identification of residues in beta-lactamase critical for binding beta-lactamase
      inhibitory protein.
AB  - beta-Lactamase inhibitory protein (BLIP) is a potent inhibitor of several beta
      lactamases including TEM-1 beta-lactamase (Ki = 0.1 nM). The co-crystal structure
      of TEM-1 beta-lactamase and BLIP has been solved, revealing the contact residues
      involved in the interface between the enzyme and inhibitor. To determine which
      residues in TEM-1 beta-lactamase are critical for binding BLIP, the method of
      monovalent phage display was employed. Random mutants of TEM-1 beta-lactamase in
      the 99-114 loop-helix and 235-240 B3 beta-strand regions were displayed as fusion
      proteins on the surface of the M13 bacteriophage. Functional mutants were
      selected based on the ability to bind BLIP. After three rounds of enrichment, the
      sequences of a collection of functional beta-lactamase mutants revealed a
      consensus sequence for the binding of BLIP. Seven loop-helix residues including
      Asp-101, Leu-102, Val-103, Ser-106, Pro-107, Thr-109, and His-112 and three B3
      beta-strand residues including Ser-235, Gly-236, and Gly-238 were found to be
      critical for tight binding of BLIP. In addition, the selected beta-lactamase
      mutants A113L/T114R and E240K were found to increase binding of BLIP by over 6-
      and 11-fold, respectively. Combining these substitutions resulted in 550-fold
      tighter binding between the enzyme and BLIP with a Ki of 0.40 pM. These results
      reveal that the binding between TEM-1 beta-lactamase and BLIP can be improved and
      that there are a large number of sequences consistent with tight binding between
      BLIP and beta-lactamase.

PMID- 10066751
TI  - Cbfa1 isoforms exert functional differences in osteoblast differentiation.
AB  - Cbfa1 is an essential transcription factor for osteoblast differentiation and
      bone formation. We investigated functional differences among three isoforms of
      Cbfa1: Type I (originally reported as Pebp2alphaA by Ogawa et al. (Ogawa, E.,
      Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., and
      Ito, Y. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6859-6863), Type II
      (originally reported as til-1 by Stewart et al. (Stewart, M., Terry, A., Hu, M.,
      O'Hara, M., Blyth, K., Baxter, E., Cameron, E., Onions, D. E., and Neil, J. C.
      (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 8646-8651), and Type III (originally
      reported as Osf2/Cbfa1 by Ducy et al. (Ducy, P., Zhang, R., Geoffroy, V., Ridall,
      A. L., and Karsenty, G. (1997) Cell 89, 747-754). A reverse transcriptase
      polymerase chain reaction analysis demonstrated that these isoforms were
      expressed in adult mouse bones. The transient transfection of Type I or Type II
      Cbfa1 in a mouse fibroblastic cell line, C3H10T1/2, induced the expression of
      alkaline phosphatase (ALP) activity. This induction was synergistically enhanced
      by the co-introduction of Xenopus BMP-4 cDNA. In contrast, the transient
      transfection of Type III cDNA induced no ALP activity. In C3H10T1/2 cells stably
      transfected with each isoform of Cbfa1, the gene expression of ALP was also
      strongly induced in cells transfected with Type I and Type II Cbfa1 but not in
      cells with Type III Cbfa1. Osteocalcin, osteopontin,and type I collagen gene
      expressions were induced or up-regulated in all of the cells stably transfected
      with each isoform of Cbfa1, and Type II transfected cells exhibited the highest
      expression level of osteocalcin gene. A luciferase reporter gene assay using a
      6XOSE2-SV40 promoter (6 tandem binding elements for Cbfa1 ligated in front of the
      SV40 promoter sequence), a mouse osteocalcin promoter, and a mouse osteopontin
      promoter revealed the differences in the transcriptional induction of target
      genes by each Cbfa1 isoform with or without its beta-subunit. These results
      suggest that all three of the Cbfa1 isoforms used in the present study are
      involved in the stimulatory action of osteoblast differentiation, but they exert
      different functions in the process of osteoblast differentiation.

PMID- 10066752
TI  - Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma
      membrane cholesterol.
AB  - Class I P-glycoproteins (Pgp) confer multidrug resistance in tumors, but the
      physiologic function of Pgp in normal tissues remains uncertain. In cells derived
      from tissues that normally express Pgp, recent data suggest a possible role for
      Pgp in cholesterol trafficking from the plasma membrane to the endoplasmic
      reticulum. We investigated the esterification of plasma membrane cholesterol
      under basal conditions and in response to sphingomyelinase treatment in
      transfected and drug-selected cell lines expressing differing amounts of
      functional class I Pgp. Compared with parental NIH 3T3 fibroblasts, cells
      transfected with human multidrug resistance (MDR1) Pgp esterified more
      cholesterol both without and with sphingomyelinase. Esterification also was
      greater in drug-selected Dox 6 myeloma cells than parental 8226 cells, which
      express low and non-immunodetectable amounts of Pgp, respectively. However, no
      differences in total plasma membrane cholesterol were detected. Transfection of
      fibroblasts with the multidrug resistance-associated protein (MRP) did not alter
      esterification, showing that cholesterol trafficking was not generally affected
      by ATP-binding cassette transporters. Steroidal (progesterone,
      dehydroepiandrosterone) and non-steroidal antagonists (verapamil, PSC 833,
      LY335979, and GF120918) were evaluated for effects on both cholesterol
      trafficking and the net content of 99mTc-Sestamibi, a reporter of drug transport
      activity mediated by Pgp. In Pgp-expressing cells treated with nonselective and
      selective inhibitors, both the kinetics and efficacy of inhibition of cholesterol
      esterification differed from the antagonism of drug transport mediated by Pgp.
      Thus, although the data show that greater expression of class I Pgp within a
      given cell type is associated with enhanced esterification of plasma membrane
      cholesterol in support of a physiologic function for Pgp in facilitating
      cholesterol trafficking, the molecular mechanism is dissociated from the
      conventional drug transport activity of Pgp.

PMID- 10066753
TI  - Characterization of the nucleoside triphosphatase activity of poliovirus protein
      2C reveals a mechanism by which guanidine inhibits poliovirus replication.
AB  - The highly conserved non-structural protein 2C of picornaviruses is involved in
      viral genome replication and encapsidation and in the rearrangement of
      intracellular structures. 2C binds RNA, has nucleoside triphosphatase activity,
      and shares three motifs with superfamily III helicases. Motifs "A" and "B" are
      involved in nucleotide triphosphate (NTP) binding and hydrolysis, whereas a
      function for motif "C" has not yet been demonstrated. Poliovirus RNA replication
      is inhibited by millimolar concentrations of guanidine hydrochloride (GdnHCl).
      Resistance and dependence to GdnHCl map to 2C. To characterize the nucleoside
      triphosphatase activity of 2C, we purified poliovirus recombinant 2C fused to
      glutathione S-transferase (GST-2C) from Escherichia coli. GST-2C hydrolyzed ATP
      with a Km of 0.7 mM. Other NTPs, including GTP, competed with ATP for binding to
      2C but were poor substrates for hydrolysis. Mutation of conserved residues in
      motif A and B abolished ATPase activity, as did mutation of the conserved
      asparagine residue in motif C, an observation indicating the involvement of this
      motif in ATP hydrolysis. GdnHCl at millimolar concentrations inhibited ATP
      hydrolysis. Mutations in 2C that confer poliovirus resistant to or dependent on
      GdnHCl increased the tolerance to GdnHCl up to 100-fold.

PMID- 10066754
TI  - A phosphatidylinositol 3-kinase-dependent pathway that differentially regulates c
      Raf and A-Raf.
AB  - Cytokines trigger the rapid assembly of multimolecular signaling complexes that
      direct the activation of downstream protein kinase cascades. Two protein kinases
      that have been linked to growth factor-regulated proliferation and survival are
      mitogen-activated protein/ERK kinase (MEK) and its downstream target Erk, a
      member of the mitogen-activated protein kinase family. Using complementary
      pharmacological and genetic approaches, we demonstrate that MEK and Erk
      activation requires a phosphatidylinositol 3-kinase (PI3-K)-generated signal in
      an interleukin (IL)-3-dependent myeloid progenitor cell line. Analysis of the
      upstream pathway leading to MEK activation revealed that inhibition of PI3-K did
      not block c-Raf activation, whereas MEK activation was effectively blocked under
      these conditions. Furthermore, agents that elevated cAMP suppressed IL-3-induced
      c-Raf activation but did not inhibit MEK activation. Because c-Raf activation and
      MEK activation were inversely affected by PI3-K- and cAMP-dependent pathways, we
      examined whether IL-3 activated the alternative Raf isoforms A-Raf and B-Raf.
      Although IL-3 did not activate B-Raf, A-Raf was activated by the cytokine.
      Moreover, A-Raf activation, like MEK activation, was blocked by inhibition of PI3
      K but was insensitive to cAMP. Experiments with dominant negative mutants of the
      Raf isoforms showed that overexpression of dominant negative c-Raf did not
      prevent MEK activation. However, dominant negative A-Raf effectively blocked MEK
      activation, suggesting that activation of the MEK-Erk signaling cascade is
      mediated through A-Raf. Taken together, these results suggest that IL-3 receptors
      engage and activate both c-Raf and A-Raf in hemopoietic cells. However, these
      intermediates are differentially regulated by upstream signaling cascades and
      selectively coupled to downstream signaling pathways.

PMID- 10066755
TI  - Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier.
AB  - Lactoferrin (Lf) is an iron-binding protein involved in host defense against
      infection and severe inflammation; it accumulates in the brain during
      neurodegenerative disorders. Before determining Lf function in brain tissue, we
      investigated its origin and demonstrate here that it crosses the blood-brain
      barrier. An in vitro model of the blood-brain barrier was used to examine the
      mechanism of Lf transport to the brain. We report that differentiated bovine
      brain capillary endothelial cells exhibited specific high (Kd = 37.5 nM; n =
      90,000/cell) and low (Kd = 2 microM; n = 900,000 sites/cell) affinity binding
      sites. Only the latter were present on nondifferentiated cells. The surface-bound
      Lf was internalized only by the differentiated cell population leading to the
      conclusion that Lf receptors were acquired during cell differentiation. A
      specific unidirectional transport then occurred via a receptor-mediated process
      with no apparent intraendothelial degradation. We further report that iron may
      cross the bovine brain capillary endothelial cells as a complex with Lf. Finally,
      we show that the low density lipoprotein receptor-related protein might be
      involved in this process because its specific antagonist, the receptor-associated
      protein, inhibits 70% of Lf transport.

PMID- 10066756
TI  - Molecular basis of the interaction between plasma platelet-activating factor
      acetylhydrolase and low density lipoprotein.
AB  - The platelet-activating factor acetylhydrolases are enzymes that were initially
      characterized by their ability to hydrolyze platelet-activating factor (PAF). In
      human plasma, PAF acetylhydrolase (EC 3.1.1.47) circulates in a complex with low
      density lipoproteins (LDL) and high density lipoproteins (HDL). This association
      defines the physical state of PAF acetylhydrolase, confers a long half-life, and
      is a major determinant of its catalytic efficiency in vivo. The lipoprotein
      associated enzyme accounts for all of the PAF hydrolysis in plasma but only two
      thirds of the protein mass. To characterize the enzyme-lipoprotein interaction,
      we employed site-directed mutagenesis techniques. Two domains within the primary
      sequence of human PAF acetylhydrolase, tyrosine 205 and residues 115 and 116,
      were important for its binding to LDL. Mutation or deletion of those sequences
      prevented the association of the enzyme with lipoproteins. When residues 115 and
      116 from human PAF acetylhydrolase were introduced into mouse PAF acetylhydrolase
      (which normally does not associate with LDL), the mutant mouse PAF
      acetylhydrolase associated with lipoproteins. To analyze the role of
      apolipoprotein (apo) B100 in the formation of the PAF acetylhydrolase-LDL
      complex, we tested the ability of PAF acetylhydrolase to bind to lipoproteins
      containing truncated forms of apoB. These studies indicated that the carboxyl
      terminus of apoB plays a key role in the association of PAF acetylhydrolase with
      LDL. These data on the molecular basis of the PAF acetylhydrolase-LDL association
      provide a new level of understanding regarding the pathway for the catabolism of
      PAF in human blood.

PMID- 10066757
TI  - RAG1 and RAG2 cooperate in specific binding to the recombination signal sequence
      in vitro.
AB  - An essential step in the development of the vertebrate immune system is the DNA
      level rearrangement of the antigen receptor genes. This process, termed "V(D)J
      recombination," begins with DNA cleavage at the appropriate sites mediated by the
      two proteins RAG1 and RAG2. We report here that the two proteins cooperate to
      bind DNA with significantly higher specificity than either protein alone. Gel
      purification of the triple complex is performed in the absence of any cross
      linking agents. Both proteins remain present in the complex, and UV cross-linking
      using iodouridine-containing probes shows that RAG1 makes close contacts in both
      the heptamer and nonamer motifs. The two proteins are also shown to associate
      with each other in the absence of any DNA. These findings refine our
      understanding of the protein-DNA interactions that accompany cleavage at the
      recombination signals.

PMID- 10066758
TI  - Identification of protein-disulfide isomerase activity in fibronectin.
AB  - Assembly and degradation of fibronectin-containing extracellular matrices are
      dynamic processes that are up-regulated during wound healing, embryogenesis, and
      metastasis. Although several of the early steps leading to fibronectin deposition
      have been identified, the mechanisms leading to the accumulation of fibronectin
      in disulfide-stabilized multimers are largely unknown. Disulfide-stabilized
      fibronectin multimers are thought to arise through intra- or intermolecular
      disulfide exchange. Several proteins involved in disulfide exchange reactions
      contain the sequence Cys-X-X-Cys in their active sites, including thioredoxin and
      protein-disulfide isomerase. The twelfth type I module of fibronectin (I12)
      contains a Cys-X-X-Cys motif, suggesting that fibronectin may have the intrinsic
      ability to catalyze disulfide bond rearrangement. Using an established protein
      refolding assay, we demonstrate here that fibronectin has protein-disulfide
      isomerase activity and that this activity is localized to the carboxyl-terminal
      type I module I12. I12 was as active on an equal molar basis as intact
      fibronectin, indicating that most of the protein-disulfide isomerase activity of
      fibronectin is localized to I12. Moreover, the protein-disulfide isomerase
      activity of fibronectin appears to be partially cryptic since limited proteolysis
      of I10-I12 increased its isomerase activity and dramatically enhanced the rate of
      RNase refolding. This is the first demonstration that fibronectin contains
      protein-disulfide isomerase activity and suggests that cross-linking of
      fibronectin in the extracellular matrix may be catalyzed by a disulfide isomerase
      activity contained within the fibronectin molecule.

PMID- 10066759
TI  - Binding of Cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide
      reductase from Lactobacillus leichmannii. Identification of dimethylbenzimidazole
      as the axial ligand.
AB  - The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii
      catalyzes the reduction of nucleoside 5'-triphosphates to 2'-deoxynucleoside 5'
      triphosphates and uses coenzyme B12, adenosylcobalamin (AdoCbl), as a cofactor.
      Use of a mechanism-based inhibitor, 2'-deoxy-2'-methylenecytidine 5'
      triphosphate, and isotopically labeled RTPR and AdoCbl in conjunction with EPR
      spectroscopy has allowed identification of the lower axial ligand of
      cob(II)alamin when bound to RTPR. In common with the AdoCbl-dependent enzymes
      catalyzing irreversible heteroatom migrations and in contrast to the enzymes
      catalyzing reversible carbon skeleton rearrangements, the dimethylbenzimidazole
      moiety of the cofactor is not displaced by a protein histidine upon binding to
      RTPR.

PMID- 10066760
TI  - Both group IB and group IIA secreted phospholipases A2 are natural ligands of the
      mouse 180-kDa M-type receptor.
AB  - Snake venom and mammalian secreted phospholipases A2 (sPLA2s) have been
      associated with toxic (neurotoxicity, myotoxicity, etc.), pathological
      (inflammation, cancer, etc.), and physiological (proliferation, contraction,
      secretion, etc.) processes. Specific membrane receptors (M and N types) for
      sPLA2s have been initially identified with snake venom sPLA2s as ligands, and the
      M-type 180-kDa receptor was cloned from different animal species. This paper
      addresses the problem of the endogenous ligands of the M-type receptor.
      Recombinant group IB and group IIA sPLA2s from human and mouse species have been
      prepared and analyzed for their binding properties to M-type receptors from
      different animal species. Both mouse group IB and group IIA sPLA2s are high
      affinity ligands (in the 1-10 nM range) for the mouse M-type receptor. These two
      sPLA2s are expressed in the mouse tissues where the M-type receptor is also
      expressed, making it likely that both types of sPLA2s are physiological ligands
      of the mouse M-type receptor. This conclusion does not hold for human group IB
      and IIA sPLA2s and the cloned human M-type receptor. The two mouse sPLA2s have
      relatively high affinities for the mouse M-type receptor, but they can have much
      lower affinities for receptors from other animal species, indicating that species
      specificity exists for sPLA2 binding to M-type receptors. Caution should thus be
      exerted in avoiding mixing sPLA2s, cells, or tissues from different animal
      species in studies of the biological roles of mammalian sPLA2s associated with an
      action through their membrane receptors.

PMID- 10066761
TI  - Binding of the transition state analog MgADP-fluoroaluminate to F1-ATPase.
AB  - Escherichia coli F1-ATPase from mutant betaY331W was potently inhibited by
      fluoroaluminate plus MgADP but not by MgADP alone. beta-Trp-331 fluorescence was
      used to measure MgADP binding to catalytic sites. Fluoroaluminate induced a very
      large increase in MgADP binding affinity at catalytic site one, a smaller
      increase at site two, and no effect at site three. Mutation of either of the
      critical catalytic site residues beta-Lys-155 or beta-Glu-181 to Gln abolished
      the effects of fluoroaluminate on MgADP binding. The results indicate that the
      MgADP-fluoroaluminate complex is a transition state analog and independently
      demonstrate that residues beta-Lys-155 and (particularly) beta-Glu-181 are
      important for generation and stabilization of the catalytic transition state.
      Dicyclohexylcarbodiimide-inhibited enzyme, with 1% residual steady-state ATPase,
      showed normal transition state formation as judged by fluoroaluminate-induced
      MgADP binding affinity changes, consistent with a proposed mechanism by which
      dicyclohexylcarbodiimide prevents a conformational interaction between catalytic
      sites but does not affect the catalytic step per se. The fluorescence technique
      should prove valuable for future transition state studies of F1-ATPase.

PMID- 10066762
TI  - Fas-induced B cell apoptosis requires an increase in free cytosolic magnesium as
      an early event.
AB  - Ligation of the Fas molecule expressed on the surface of a cell initiates
      multiple signaling pathways that result in the apoptotic death of that cell. We
      have examined Mg2+ mobilization as well as Ca2+ mobilization in B cells
      undergoing Fas-initiated apoptosis. Our results indicate that cytosolic levels of
      free (non-complexed) Mg2+ ([Mg2+]i) and Ca2+ ([Ca2+]i) increase in cells
      undergoing apoptosis. Furthermore, the percentages of cells mobilizing Mg2+,
      fragmenting DNA, or externalizing phosphatidylserine (PS) increase in parallel as
      the concentration of anti-Fas monoclonal antibody is raised. Kinetic analysis
      suggests that Mg2+ mobilization is an early event in apoptosis, clearly preceding
      DNA fragmentation and probably occurring prior to externalization of PS as well.
      The source of Mg2+ that produces the increases in [Mg2+]i is intracellular and
      most likely is the mitochondria. Extended pretreatment of B cells with carbonyl
      cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial oxidative
      phosphorylation, produces proportional decreases in the percentage of cells
      mobilizing Mg2+, fragmenting DNA, and externalizing PS in response to anti-Fas
      monoclonal antibody treatment. These observations are consistent with the
      hypothesis that elevated [Mg2+]i is required for apoptosis. Furthermore, we
      propose that the increases in [Mg2+]i function not only as cofactors for Mg2+
      dependent endonucleases, but also to facilitate the release of cytochrome c from
      the mitochondria, which drives many of the post-mitochondrial, caspase-mediated
      events in apoptotic cells.

PMID- 10066763
TI  - Up-regulation of the Pit-2 phosphate transporter/retrovirus receptor by protein
      kinase C epsilon.
AB  - The membrane receptors for the gibbon ape leukemia retrovirus and the amphotropic
      murine retrovirus serve normal cellular functions as sodium-dependent phosphate
      transporters (Pit-1 and Pit-2, respectively). Our earlier studies established
      that activation of protein kinase C (PKC) by treatment of cells with phorbol 12
      myristate 13-acetate (PMA) enhanced sodium-dependent phosphate (Na/Pi) uptake.
      Studies now have been carried out to determine which type of Na/Pi transporter
      (Pit-1 or Pit-2) is regulated by PKC and which PKC isotypes are involved in the
      up-regulation of Na/Pi uptake by the Na/Pi transporter/viral receptor. It was
      found that the activation of short term (2-min) Na/Pi uptake by PMA is abolished
      when cells are infected with amphotropic murine retrovirus (binds Pit-2 receptor)
      but not with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating
      that Pit-2 is the form of Na/Pi transporter/viral receptor regulated by PKC. The
      PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan
      PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype
      inhibitor Go 6976, suggesting that a novel PKC isotype is required to regulate
      Pit-2. Overexpression of PKCepsilon, but not of PKCalpha, -delta, or -zeta, was
      found to mimic the activation of Na/Pi uptake. To further establish that
      PKCepsilon is involved in the regulation of Pit-2, cells were treated with
      PKCepsilon-selective antisense oligonucleotides. Treatment with PKCepsilon
      antisense oligonucleotides decreased the PMA-induced activation of Na/Pi uptake.
      These results indicate that PMA-induced stimulation of Na/Pi uptake by Pit-2 is
      specifically mediated through activation of PKCepsilon.

PMID- 10066764
TI  - Nuclear factor I-mediated repression of the mouse mammary tumor virus promoter is
      abrogated by the coactivators p300/CBP and SRC-1.
AB  - To better understand the function of nuclear factor I (NFI) proteins in
      transcription, we have used transient transfection assays to assess
      transcriptional modulation by NFI proteins on the NFI-dependent mouse mammary
      tumor virus (MMTV) promoter. Expression of NFI-C or NFI-X, but not NFI-A or NFI-B
      proteins, represses glucocorticoid induction of the MMTV promoter in HeLa cells.
      Repression is DNA binding-independent as a deletion construct expressing the NH2
      terminal 160 residues of NFI-C represses but does not bind DNA. Repression by NFI
      C is cell type-dependent and occurs in HeLa and COS-1 cells but not 293 or JEG-3
      cells. NFI-C does not repress progesterone induction of the MMTV promoter in HeLa
      cells, suggesting that progesterone induction of the promoter differs
      mechanistically from glucocorticoid induction. NFI-C-mediated repression is
      alleviated by overexpression of glucocorticoid receptor (GR), suggesting that NFI
      C represses the MMTV promoter by preventing GR function. However, repression by
      NFI-C occurs with only a subset of glucocorticoid-responsive promoters, as the
      chimeric NFIGREbeta-gal promoter that is activated by GR is not repressed by NFI
      C. Since the coactivator proteins p300/CBP, SRC-1A, and RAC3 had previously been
      shown to function at steroid hormone-responsive promoters, we asked whether they
      could influence NFI-C-mediated repression of MMTV expression. Expression of
      p300/CBP or SRC-1A alleviates repression by NFI-C, whereas RAC3 has no effect.
      This abrogation of NFI-C-mediated repression by p300/CBP and SRC-1A suggests that
      repression by NFI-C may occur by interference with coactivator function at the
      MMTV promoter.

PMID- 10066765
TI  - Cloning and expression of a wheat (Triticum aestivum L.) phosphatidylserine
      synthase cDNA. Overexpression in plants alters the composition of phospholipids.
AB  - We describe the cloning of a wheat cDNA (TaPSS1) that encodes a
      phosphatidylserine synthase (PSS) and provides the first strong evidence for the
      existence of this enzyme in a higher eukaryotic cell. The cDNA was isolated on
      its ability to confer increased resistance to aluminum toxicity when expressed in
      yeast. The sequence of the predicted protein encoded by TaPSS1 shows homology to
      PSS from both yeast and bacteria but is distinct from the animal PSS enzymes that
      catalyze base-exchange reactions. In wheat, Southern blot analysis identified the
      presence of a small family of genes that cross-hybridized to TaPSS1, and Northern
      blots showed that aluminum induced TaPSS1 expression in root apices. Expression
      of TaPSS1 complemented the yeast cho1 mutant that lacks PSS activity and altered
      the phospholipid composition of wild type yeast, with the most marked effect
      being increased abundance of phosphatidylserine (PS). Arabidopsis thaliana leaves
      overexpressing TaPSS1 showed a marked enhancement in PSS activity, which was
      associated with increased biosynthesis of PS at the expense of both
      phosphatidylinositol and phosphatidylglycerol. Unlike mammalian cells where PS
      accumulation is tightly regulated even when the capacity for PS biosynthesis is
      increased, plant cells accumulated large amounts of PS when TaPSS1 was
      overexpressed. High levels of TaPSS1 expression in Arabidopsis and tobacco
      (Nicotiana tabacum) led to the appearance of necrotic lesions on leaves, which
      may have resulted from the excessive accumulation of PS. The cloning of TaPSS1
      now provides evidence that the yeast pathway for PS synthesis exists in some
      plant tissues and provides a tool for understanding the pathways of phospholipid
      biosynthesis and their regulation in plants.

PMID- 10066766
TI  - EPR spectroscopy of VO2+-ATP bound to catalytic site 3 of chloroplast F1-ATPase
      from Chlamydomonas reveals changes in metal ligation resulting from mutations to
      the phosphate-binding loop threonine (betaT168).
AB  - Site-directed mutations were made to the phosphate-binding loop threonine in the
      beta-subunit of the chloroplast F1-ATPase in Chlamydomonas (betaT168). Rates of
      photophosphorylation and ATPase-driven proton translocation measured in coupled
      thylakoids purified from betaT168D, betaT168C, and betaT168L mutants had <10% of
      the wild type rates, as did rates of Mg2+-ATPase activity of purified chloroplast
      F1-ATPase (CF1). The EPR spectra of VO2+-ATP bound to Site 3 of CF1 from wild
      type and mutants showed that EPR species C, formed exclusively upon activation,
      was altered in CF1 from each mutant in both signal intensity and in 51V hyperfine
      parameters that depend on the equatorial VO2+ ligands. These data provide the
      first direct evidence that Site 3 is a catalytic site. No significant differences
      between wild type and mutants were observed in EPR species B, the predominant
      form of the latent enzyme. Thus, the phosphate-binding loop threonine is an
      equatorial metal ligand in the activated conformation but not in the latent
      conformation of Site 3. The metal-nucleotide conformation that gives rise to
      species B is consistent with the Mg2+-ADP complex that becomes entrapped in a
      catalytic site in a manner that regulates enzymatic activity. The lack of
      catalytic function of CF1 with entrapped Mg2+-ADP may be explained in part by the
      absence of the phosphate-binding loop threonine as a metal ligand.

PMID- 10066767
TI  - Murine p38-delta mitogen-activated protein kinase, a developmentally regulated
      protein kinase that is activated by stress and proinflammatory cytokines.
AB  - The p38 mitogen-activated protein kinases (MAPK) play a crucial role in stress
      and inflammatory responses and are also involved in activation of the human
      immunodeficiency virus gene expression. We have isolated the murine cDNA clones
      encoding p38-delta MAPK, and we have localized the p38-delta gene to mouse
      chromosome 17A3-B and human chromosome 6p21.3. By using Northern and in situ
      hybridization, we have examined the expression of p38-delta in the mouse adult
      tissues and embryos. p38-delta was expressed primarily in the lung, testis,
      kidney, and gut epithelium in the adult tissues. Although p38-delta was expressed
      predominantly in the developing gut and the septum transversum in the mouse
      embryo at 9.5 days, its expression began to be expanded to many specific tissues
      in the 12.5-day embryo. At 15.5 days, p38-delta was expressed virtually in most
      developing epithelia in embryos, suggesting that p38-delta is a developmentally
      regulated MAPK. Interestingly, p38-delta and p38-alpha were similar
      serine/threonine kinases but differed in substrate specificity. Overall, p38
      delta resembles p38-gamma, whereas p38-beta resembles p38-alpha. Moreover, p38
      delta is activated by environmental stress, extracellular stimulants, and MAPK
      kinase-3, -4, -6, and -7, suggesting that p38-delta is a unique stress-responsive
      protein kinase.

PMID- 10066768
TI  - Role of aromaticity of agonist switches of angiotensin II in the activation of
      the AT1 receptor.
AB  - We have shown previously that the octapeptide angiotensin II (Ang II) activates
      the AT1 receptor through an induced-fit mechanism (Noda, K., Feng, Y. H., Liu, X.
      P., Saad, Y., Husain, A., and Karnik, S. S. (1996) Biochemistry 35, 16435-16442).
      In this activation process, interactions between Tyr4 and Phe8 of Ang II with
      Asn111 and His256 of the AT1 receptor, respectively, are essential for agonism.
      Here we show that aromaticity, primarily, and size, secondarily, of the Tyr4 side
      chain are important in activating the receptor. Activation analysis of AT1
      receptor position 111 mutants by various Ang II position 4 analogues suggests
      that an amino-aromatic bonding interaction operates between the residue Asn111 of
      the AT1 receptor and Tyr4 of Ang II. Degree and potency of AT1 receptor
      activation by Ang II can be recreated by a reciprocal exchange of aromatic and
      amide groups between positions 4 and 111 of Ang II and the AT1 receptor,
      respectively. In several other bonding combinations, set up between Ang II
      position 4 analogues and receptor mutants, the gain of affinity is not
      accompanied by gain of function. Activation analysis of position 256 receptor
      mutants by Ang II position 8 analogues suggests that aromaticity of Phe8 and
      His256 side chains is crucial for receptor activation; however, a stacked rather
      than an amino-aromatic interaction appears to operate at this switch locus.
      Interaction between these residues, unlike the Tyr4:Asn111 interaction, plays an
      insignificant role in ligand docking.

PMID- 10066769
TI  - Characterization of proteoglycans synthesized by cultured corneal fibroblasts in
      response to transforming growth factor beta and fetal calf serum.
AB  - A culture system was developed to analyze the relationship between proteoglycans
      and growth factors during corneal injury. Specifically, the effects of
      transforming growth factor beta-1 (TGF-beta1) and fetal calf serum on
      proteoglycan synthesis in corneal fibroblasts were examined. Glycosaminoglycan
      synthesis and sulfation were determined using selective polysaccharidases.
      Proteoglycan core proteins were analyzed using gel electrophoresis and Western
      blotting. Cells cultured in 10% dialyzed fetal calf serum exhibited decreased
      synthesis of more highly sulfated chondroitin sulfate and heparan sulfate
      compared with cells cultured in 1% dialyzed fetal calf serum. The amount and
      sulfation of the glycosaminoglycans was not significantly influenced by TGF
      beta1. The major proteoglycan species secreted into the media were decorin and
      perlecan. Decorin was glycanated with chondroitin sulfate. Perlecan was linked to
      either chondroitin sulfate, heparan sulfate, or both chondroitin sulfate and
      heparan sulfate. Decorin synthesis was reduced by either TGF-beta1 or serum. At
      early time points, both TGF-beta1 and serum induced substantial increases in
      perlecan bearing chondroitin sulfate and/or heparan sulfate chains. In contrast,
      after extended periods in culture, the amount of perlecan bearing heparan sulfate
      chains was unaffected by TGF-beta1 and decreased by serum. The levels of perlecan
      bearing chondroitin sulfate chains were elevated with TGF-beta1 treatment and
      were decreased with serum. Because both decorin and perlecan bind growth factors
      and are proposed to modulate their activity, changes in the expression of either
      of these proteoglycans could substantially affect the cellular response to
      injury.

PMID- 10066770
TI  - Identification and structure characterization of a Cdk inhibitory peptide derived
      from neuronal-specific Cdk5 activator.
AB  - The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its
      neuronal specific activator Nck5a. The minimal activation domain of Nck5a is
      located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C.
      S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this
      work we show that a 29-residue peptide, denoted as the alphaN peptide,
      encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding
      Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho
      Cdk2-cyclin A complex, with a similar potency. Direct competition experiments
      have shown that this inhibitory peptide does not compete with Nck5a or cyclin A
      for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that
      the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex
      with respect to the peptide substrate. To understand the molecular basis of
      kinase inhibition by the peptide, we determined the structure of the peptide in
      solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The
      peptide adopts an amphipathic alpha-helical structure from residues Ser149 to
      Arg162 which can be further stabilized by the helix-stabilizing solvent
      trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase
      binding surface.

PMID- 10066771
TI  - Purification and characterization of a mitochondrial thymine glycol endonuclease
      from rat liver.
AB  - Mitochondrial DNA is exposed to oxygen radicals produced during oxidative
      phosphorylation. Accumulation of several kinds of oxidative lesions in
      mitochondrial DNA may lead to structural genomic alterations, mitochondrial
      dysfunction, and associated degenerative diseases. The pyrimidine hydrate thymine
      glycol, one of many oxidative lesions, can block DNA and RNA polymerases and
      thereby exert negative biological effects. Mitochondrial DNA repair of this
      lesion is important to ensure normal mitochondrial DNA metabolism. Here, we
      report the purification of a novel rat liver mitochondrial thymine glycol
      endonuclease (mtTGendo). By using a radiolabeled oligonucleotide duplex
      containing a single thymine glycol lesion, damage-specific incision at the
      modified thymine was observed upon incubation with mitochondrial protein
      extracts. After purification using cation exchange, hydrophobic interaction, and
      size exclusion chromatography, the most pure active fractions contained a single
      band of approximately 37 kDa on a silver-stained gel. MtTGendo is active within a
      broad KCl concentration range and is EDTA-resistant. Furthermore, mtTGendo has an
      associated apurinic/apyrimidinic-lyase activity. MtTGendo does not incise 8
      oxodeoxyguanosine or uracil-containing duplexes or thymine glycol in single
      stranded DNA. Based upon functional similarity, we conclude that mtTGendo may be
      a rat mitochondrial homolog of the Escherichia coli endonuclease III protein.

PMID- 10066772
TI  - Mapping binding domains of kininogens on endothelial cell cytokeratin 1.
AB  - Human cytokeratin 1 (CK1) in human umbilical vein endothelial cells (HUVEC) is
      expressed on their membranes and is able to bind high molecular weight kininogen
      (HK) (Hasan, A. A. K., Zisman, T., and Schmaier, A. H. (1998) Proc. Natl. Acad.
      Sci. U. S. A. 95, 3615-3620). New investigations have been performed to
      demonstrate the HK binding domain on CK1. Four overlapping recombinant (r) CK1
      proteins were produced in Escherichia coli by a glutathione S-transferase gene
      fusion system. Biotin-HK specifically bound to rCK128 and rCK131 in the presence
      of Zn2+ but not to Deleted1-6rCK131. Recombinant CK128 and rCK131 also inhibited
      biotin-HK binding to HUVEC with IC50 of 0.4 and 0.5 microM, respectively.
      Alternatively, rCK114 and Deleted1-6rCK131 did not inhibit binding at
      concentrations >/=1 microM. Seven sequential 20 amino acid peptides of CK1 were
      prepared to cover the protein coded by exons 1-3. Only the first peptide (GYG20)
      coded by exon 1 significantly inhibited HK binding to HUVEC with an IC50 of 35
      microM. Fine mapping studies isolated two overlapping peptides also coded by exon
      1 (GPV15 and PGG15) that inhibited binding to HUVEC with IC50 of 18 and 9 microM,
      respectively. A sequence scrambled peptide of PGG15 did not block binding to
      HUVEC and biotin-GPV20 specifically bound to HK. Peptides GPV15 and PGG15 also
      blocked prekallikrein activation on endothelial cells. However, inhibition of PK
      activation by peptide PGG15 occurred at 10-fold lower concentration (IC50 = 1
      microM) than inhibition of biotin-HK binding to HUVEC (IC50 = 10 microM). These
      studies indicate that HK binds to a region of 20 amino acids coded by exon 1 on
      CK1 which is carboxyl-terminal to its glycine-rich amino-terminal globular
      domain. Furthermore, HK binding to CK1 modulates PK activation on HUVEC.

PMID- 10066773
TI  - Evidence for the head domain movement of the rieske iron-sulfur protein in
      electron transfer reaction of the cytochrome bc1 complex.
AB  - The three-dimensional structure of the mitochondrial cytochrome bc1 complex
      suggests that movement of the extramembrane domain (head) of the Rieske iron
      sulfur protein (ISP) may play an important role in electron transfer. Such
      movement requires flexibility in the neck region of ISP, since the head and
      transmembrane domains of the protein are rather rigid. To test this hypothesis,
      Rhodobacter sphaeroides mutants expressing His-tagged cytochrome bc1 complexes
      with cysteine substitution at various positions in the ISP neck (residues 39-48)
      were generated and characterized. The mutants with a single cysteine substitution
      at Ala42 or Val44 and a double cysteine substitution at Val44 and Ala46 (VQA-CQC)
      or at Ala42 and Ala46 (ADVQA-CDVQC) have photosynthetic growth rates comparable
      with that of complement cells. Chromatophore membrane and intracytoplasmic
      membrane (ICM) prepared from these mutants have cytochrome bc1 complex activity
      similar to that in the complement membranes, indicating that flexibility of the
      neck region of ISP was not affected by these cysteine substitutions. Mutants with
      a double cysteine substitution at Ala42 and Val44 (ADV-CDC) or at Pro40 and Ala42
      (PSA-CSC) have a retarded (50%) or no photosynthetic growth rate, respectively.
      The ADV-CDC or PSA-CSC mutant ICM contains 20 or 0% of the cytochrome bc1 complex
      activity found in the complement ICM. However, activity can be restored by the
      treatment with beta-mercaptoethanol (beta-ME). The restored activity is
      diminished upon removal of beta-ME but is retained if the beta-ME-treated
      membrane is treated with the sulfhydryl reagent N-ethylmaleimide or p
      chloromercuribenzoic acid. These results indicate that the loss of bc1 complex
      activity in the ADV-CDC or PSA-CSC mutant membranes is due to disulfide bond
      formation, which increases the rigidity of ISP neck and, in turn, decreases the
      mobility of the head domain. Using the conditions developed for the isolation of
      His-tagged complement cytochrome bc1 complex, a two-subunit complex (cytochromes
      b and c1) is obtained from all of the double cysteine-substituted mutants. This
      suggests that introduction of two cysteines in the neck region of ISP weakens the
      interactions between cytochromes b, ISP, and subunit IV.

PMID- 10066774
TI  - Distinct contributions of residue 192 to the specificity of coagulation and
      fibrinolytic serine proteases.
AB  - Archetypal members of the chymotrypsin family of serine proteases, such as
      trypsin, chymotrypsin, and elastase, exhibit relatively broad substrate
      specificity. However, the successful development of efficient proteolytic
      cascades, such as the blood coagulation and fibrinolytic systems, required the
      evolution of proteases that displayed restricted specificity. Tissue-type
      plasminogen activator (t-PA), for example, possesses exquisitely stringent
      substrate specificity, and the molecular basis of this important biochemical
      property of t-PA remains obscure. Previous investigations of related serine
      proteases, which participate in the blood coagulation cascade, have focused
      attention on the residue that occupies position 192 (chymotrypsin numbering
      system), which plays a pivotal role in determining both the inhibitor and
      substrate specificity of these enzymes. Consequently, we created and
      characterized the kinetic properties of new variants of t-PA that contained point
      mutations at position 192. These studies demonstrated that, unlike in coagulation
      serine proteases, Gln-192 does not contribute significantly to the substrate or
      inhibitor specificity of t-PA in physiologically relevant reactions. Replacement
      of Gln-192 with a glutamic acid residue did, however, decrease the catalytic
      efficiency of mature, two-chain t-PA toward plasminogen in the absence of a
      fibrin co-factor.

PMID- 10066775
TI  - Roles for the troponin tail domain in thin filament assembly and regulation. A
      deletional study of cardiac troponin T.
AB  - Striated muscle contraction is regulated by Ca2+ binding to troponin, which has a
      globular domain and an elongated tail attributable to the NH2-terminal portion of
      the bovine cardiac troponin T (TnT) subunit. Truncation of the bovine cardiac
      troponin tail was investigated using recombinant TnT fragments and subunits TnI
      and TnC. Progressive truncation of the troponin tail caused progressively weaker
      binding of troponin-tropomyosin to actin and of troponin to actin-tropomyosin. A
      sharp drop-off in affinity occurred with NH2-terminal deletion of 119 rather than
      94 residues. Deletion of 94 residues had no effect on Ca2+-activation of the
      myosin subfragment 1-thin filament MgATPase rate and did not eliminate
      cooperative effects of Ca2+ binding. Troponin tail peptide TnT1-153 strongly
      promoted tropomyosin binding to actin in the absence of TnI or TnC. The results
      show that the anchoring function of the troponin tail involves interactions with
      actin as well as with tropomyosin and has comparable importance in the presence
      or absence of Ca2+. Residues 95-153 are particularly important for anchoring, and
      residues 95-119 are crucial for function or local folding. Because striated
      muscle regulation involves switching among the conformational states of the thin
      filament, regulatory significance for the troponin tail may arise from its
      prominent contribution to the protein-protein interactions within these
      conformations.

PMID- 10066776
TI  - Lower plasma levels and accelerated clearance of high density lipoprotein (HDL)
      and non-HDL cholesterol in scavenger receptor class B type I transgenic mice.
AB  - Recent studies have indicated that the scavenger receptor class B type I (SR-BI)
      may play an important role in the uptake of high density lipoprotein (HDL)
      cholesteryl ester in liver and steroidogenic tissues. To investigate the in vivo
      effects of liver-specific SR-BI overexpression on lipid metabolism, we created
      several lines of SR-BI transgenic mice with an SR-BI genomic construct where the
      SR-BI promoter region had been replaced by the apolipoprotein (apo)A-I promoter.
      The effect of constitutively increased SR-BI expression on plasma HDL and non-HDL
      lipoproteins and apolipoproteins was characterized. There was an inverse
      correlation between SR-BI expression and apoA-I and HDL cholesterol levels in
      transgenic mice fed either mouse chow or a diet high in fat and cholesterol. An
      unexpected finding in the SR-BI transgenic mice was the dramatic impact of the SR
      BI transgene on non-HDL cholesterol and apoB whose levels were also inversely
      correlated with SR-BI expression. Consistent with the decrease in plasma HDL and
      non-HDL cholesterol was an accelerated clearance of HDL, non-HDL, and their major
      associated apolipoproteins in the transgenics compared with control animals.
      These in vivo studies of the effect of SR-BI overexpression on plasma
      lipoproteins support the previously proposed hypothesis that SR-BI accelerates
      the metabolism of HDL and also highlight the capacity of this receptor to
      participate in the metabolism of non-HDL lipoproteins.

PMID- 10066777
TI  - The heparin/heparan sulfate-binding site on apo-serum amyloid A. Implications for
      the therapeutic intervention of amyloidosis.
AB  - Serum amyloid A isoforms, apoSAA1 and apoSAA2, are apolipoproteins of unknown
      function that become major components of high density lipoprotein (HDL) during
      the acute phase of an inflammatory response. ApoSAA is also the precursor of
      inflammation-associated amyloid, and there is strong evidence that the formation
      of inflammation-associated and other types of amyloid is promoted by heparan
      sulfate (HS). Data presented herein demonstrate that both mouse and human apoSAA
      contain binding sites that are specific for heparin and HS, with no binding for
      the other major glycosaminoglycans detected. Cyanogen bromide-generated peptides
      of mouse apoSAA1 and apoSAA2 were screened for heparin binding activity. Two
      peptides, an apoSAA1-derived 80-mer (residues 24-103) and a smaller carboxyl
      terminal 27-mer peptide of apoSAA2 (residues 77-103), were retained by a heparin
      column. A synthetic peptide corresponding to the CNBr-generated 27-mer also bound
      heparin, and by substituting or deleting one or more of its six basic residues
      (Arg-83, His-84, Arg-86, Lys-89, Arg-95, and Lys-102), their relative importance
      for heparin and HS binding was determined. The Lys-102 residue appeared to be
      required only for HS binding. The residues Arg-86, Lys-89, Arg-95, and Lys-102
      are phylogenetically conserved suggesting that the heparin/HS binding activity
      may be an important aspect of the function of apoSAA. HS linked by its carboxyl
      groups to an Affi-Gel column or treated with carbodiimide to block its carboxyl
      groups lost the ability to bind apoSAA. HDL-apoSAA did not bind to heparin;
      however, it did bind to HS, an interaction to which apoA-I contributed. Results
      from binding experiments with Congo Red-Sepharose 4B columns support the
      conclusions of a recent structural study which found that heparin binding domains
      have a common spatial distance of about 20 A between their two outer basic
      residues. Our present work provides direct evidence that apoSAA can associate
      with HS (and heparin) and that the occupation of its binding site by HS, and HS
      analogs, likely caused the previously reported increase in amyloidogenic
      conformation (beta-sheet) of apoSAA2 (McCubbin, W. D., Kay, C. M.,
      Narindrasorasak, S., and Kisilevsky, R. (1988) Biochem. J. 256, 775-783) and
      their amyloid-suppressing effects in vivo (Kisilevsky, R., Lemieux, L. J.,
      Fraser, P. E., Kong, X., Hultin, P. G., and Szarek, W. A. (1995) Nat. Med. 1, 143
      147), respectively.

PMID- 10066778
TI  - Allosteric control of three B12-dependent (class II) ribonucleotide reductases.
      Implications for the evolution of ribonucleotide reduction.
AB  - Three separate classes of ribonucleotide reductases are known, each with a
      distinct protein structure. One common feature of all enzymes is that a single
      protein generates each of the four deoxyribonucleotides. Class I and III enzymes
      contain an allosteric substrate specificity site capable of binding effectors
      (ATP or various deoxyribonucleoside triphosphates) that direct enzyme
      specificity. Some (but not all) enzymes contain a second allosteric site that
      binds only ATP or dATP. Binding of dATP to this site inhibits the activity of
      these enzymes. X-ray crystallography has localized the two sites within the
      structure of the Escherichia coli class I enzyme and identified effector-binding
      amino acids. Here, we have studied the regulation of three class II enzymes, one
      from the archaebacterium Thermoplasma acidophilum and two from eubacteria
      (Lactobacillus leichmannii and Thermotoga maritima). Each enzyme has an
      allosteric site that binds ATP or various deoxyribonucleoside triphosphates and
      that regulates its substrate specificity according to the same rules as for class
      I and III enzymes. dATP does not inhibit enzyme activity, suggesting the absence
      of a second active allosteric site. For the L. leichmannii and T. maritima
      enzymes, binding experiments also indicate the presence of only one allosteric
      site. Their primary sequences suggest that these enzymes lack the structural
      requirements for a second site. In contrast, the T. acidophilum enzyme binds dATP
      at two separate sites, and its sequence contains putative effector-binding amino
      acids for a second site. The presence of a second site without apparent
      physiological function leads to the hypothesis that a functional site was present
      early during the evolution of ribonucleotide reductases, but that its function
      was lost from the T. acidophilum enzyme. The other two B12 enzymes lost not only
      the function, but also the structural basis for the site. Also a large subgroup
      (Ib) of class I enzymes, but none of the investigated class III enzymes, has lost
      this site. This is further indirect evidence that class II and I enzymes may have
      arisen by divergent evolution from class III enzymes.

PMID- 10066779
TI  - Nitric oxide donors induce stress signaling via ceramide formation in rat renal
      mesangial cells.
AB  - Exogenous NO is able to trigger apoptosis of renal mesangial cells, and thus may
      contribute to acute lytic phases as well as to resolution of glomerulonephritis.
      However, the mechanism involved in these events is still unclear. We report here
      that chronic exposure of renal mesangial cells for 24 h to compounds releasing
      NO, including spermine-NO, (Z)-1-{N-methyl-N-[6-(N
      methylammoniohexyl)amino]}diazen-1-ium-1, 2-diolate (MAHMA-NO), S
      nitrosoglutathione (GS-NO), and S-nitroso-N-acetyl-D,L-penicillamine (SNAP)
      results in a potent and dose-dependent increase in the lipid signaling molecule
      ceramide. Time courses reveal that significant effects occur after 2-4 h of
      stimulation with NO donors and reach maximal levels after 24 h of stimulation. No
      acute (within minutes) ceramide production can be detected. When cells were
      stimulated with NO donors in the presence of phorbol ester, a direct activator of
      protein kinase C, both ceramide production and DNA fragmentation are completely
      abolished. Furthermore, addition of exogenous ceramide partially reversed the
      inhibitory effect of phorbol ester on apoptosis, thus suggesting a negative
      regulation of protein kinase C on ceramide formation and apoptosis. In contrast
      to exogenous NO, tumor necrosis factor (TNF)-alpha stimulates a very rapid and
      transient increase in ceramide levels within minutes but fails to induce the late
      phase ceramide formation. Moreover, TNF fails to induce apoptosis in mesangial
      cells. Interestingly, NO and TNFalpha cause a chronic activation of acidic and
      neutral sphingomyelinases, the ceramide-generating enzymes, whereas acidic and
      neutral ceramidases, the ceramide-metabolizing enzymes, are inhibited by NO, but
      potently stimulated by TNFalpha. Furthermore, in the presence of an acidic
      ceramidase inhibitor, N-oleoylethanolamine, TNFalpha leads to a sustained
      accumulation of ceramide and in parallel induces DNA fragmentation. In summary,
      our data demonstrate that exogenous NO causes a chronic up-regulation of ceramide
      levels in mesangial cells by activating sphingomyelinases and concomitantly
      inhibiting ceramidases, and that particularly the late-phase of ceramide
      generation may be responsible for the further processing of a proapoptotic
      signal.

PMID- 10066780
TI  - CREB-binding [corrected] protein interacts with the homeodomain protein Cdx2 and
      enhances transcriptional activity.
AB  - Cdx2 encodes for a homeodomain protein that is expressed in intestinal epithelial
      cells. The Cdx2 protein triggers intestinal differentiation in cell lines and is
      necessary for maintenance of the intestinal phenotype in mice. CBP (cAMP response
      element-binding protein) is a transcriptional co-activator that interacts with
      many transcription factors and components of the basal transcriptional machinery.
      In this study, we demonstrate that CBP is markedly induced upon differentiation
      of the Caco-2 intestinal cell line and augments Cdx2-dependent transcriptional
      activity. Cdx2 interacts with the amino-terminal domain of CBP, and the two
      proteins coexist in vivo within the same nuclear protein complex. Moreover,
      expression of the CBP domain that interacts with Cdx2 acts as a dominant-negative
      inhibitor of transcriptional activation by Cdx2. These findings demonstrate a
      direct interaction between an intestinal homeodomain protein and CBP and suggest
      that CBP participates in the network of transcriptional proteins that direct
      intestinal differentiation.

PMID- 10066781
TI  - 'Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions and
      facilitates their cleavage by phage resolution enzymes.
AB  - Genetic and biochemical studies have indicated that mismatch repair proteins can
      interact with recombination intermediates. In this study, gel shift assays and
      electron microscopic analysis were used to show that the Saccharomyces cerevisiae
      MSH2/6 complex binds to Holliday junctions and has an affinity and specificity
      for them that is at least as high as it has as for mispaired bases. Under
      equilibrium binding conditions, the MSH2/6 complex had a Kd of binding to
      Holliday junctions of 0.5 nM. The MSH2/6 complex enhanced the cleavage of
      Holliday junctions by T4 endonuclease VII and T7 endonuclease I. This is
      consistent with the view that the MSH2/6 complex can function in both mismatch
      repair and the resolution of recombination intermediates as predicted by genetic
      studies.

PMID- 10066782
TI  - Disulfide bond structure and N-glycosylation sites of the extracellular domain of
      the human interleukin-6 receptor.
AB  - The high affinity interleukin-6 (IL-6) receptor is a hexameric complex consisting
      of two molecules each of IL-6, IL-6 receptor (IL-6R), and the high affinity
      converter and signaling molecule, gp130. The extracellular "soluble" part of the
      IL-6R (sIL-6R) consists of three domains: an amino-terminal Ig-like domain and
      two fibronectin-type III (FN III) domains. The two FN III domains comprise the
      cytokine-binding domain defined by a set of 4 conserved cysteine residues and a
      WSXWS sequence motif. Here, we have determined the disulfide structure of the
      human sIL-6R by peptide mapping in the absence and presence of reducing agent.
      Mass spectrometric analysis of these peptides revealed four disulfide bonds and
      two free cysteines. The disulfides Cys102-Cys113 and Cys146-Cys157 are consistent
      with known cytokine-binding domain motifs, and Cys28-Cys77 with known Ig
      superfamily domains. An unusual cysteine connectivity between Cys6-Cys174, which
      links the Ig-like and NH2-terminal FN III domains causing them to fold back onto
      each other, has not previously been observed among cytokine receptors. The two
      free cysteines (Cys192 and Cys258) were detected as cysteinyl-cysteines, although
      a small proportion of Cys258 was reactive with the alkylating agent 4
      vinylpyridine. Of the four potential N-glycosylation sites, carbohydrate moieties
      were identified on Asn36, Asn74, and Asn202, but not on Asn226.

PMID- 10066783
TI  - Alternative endocytic pathway for immunoglobulin A Fc receptors (CD89) depends on
      the lack of FcRgamma association and protects against degradation of bound
      ligand.
AB  - IgA is the most abundant immunoglobulin in mucosal areas but is only the second
      most common antibody isotype in serum because it is catabolized faster than IgG.
      IgA exists in monomeric and polymeric forms that function through receptors
      expressed on effector cells. Here, we show that IgA Fc receptor(s) (FcalphaR) are
      expressed with or without the gamma chain on monocytes and neutrophils. gamma
      less FcalphaR represent a significant fraction of surface FcalphaR molecules even
      on cells overexpressing the gamma chain. The FcalphaR-gamma2 association is up
      regulated by phorbol esters and interferon-gamma. To characterize gamma-less
      FcalphaR functionally, we generated mast cell transfectants expressing wild-type
      human FcalphaR or a receptor with a point mutation (Arg --> Leu at position 209)
      which was unable to associate with the gamma chain. Mutant gamma-less FcalphaR
      bound monomeric and polymeric human IgA1 or IgA2 but failed to induce exocytosis
      after receptor clustering. The two types of transfectant showed similar kinetics
      of FcalphaR-mediated endocytosis; however, the endocytosis pathways of the two
      types of receptor differed. Whereas mutant FcalphaR were localized mainly in
      early endosomes, those containing FcalphaR-gamma2 were found in endo-lysosomal
      compartments. Mutant gamma-less FcalphaR recycled the internalized IgA toward the
      cell surface and protected against IgA degradation. Cells expressing the two
      forms of FcalphaR, associated or unassociated with gamma chains, may thus have
      differential functions either by degrading IgA antibody complexes or by recycling
      serum IgA.

PMID- 10066784
TI  - Transglutaminase cross-linking properties of the small proline-rich 1 family of
      cornified cell envelope proteins. Integration with loricrin.
AB  - Small proline-rich 1 (SPR1) proteins are important for barrier function in
      stratified squamous epithelia. To explore their properties, we expressed in
      bacteria a recombinant human SPR1 protein and isolated native SPR1 proteins from
      cultured mouse keratinocytes. By circular dichroism, they possess no alpha or
      beta structure but have some organized structure associated with their central
      peptide repeat domain. The transglutaminase (TGase) 1 and 3 enzymes use the SPR1
      proteins as complete substrates in vitro but in different ways: head domain A
      sequences at the amino terminus were used preferentially for cross-linking by
      TGase 3, whereas those in head domain B sequences were used for cross-linking by
      TGase 1. The TGase 2 enzyme cross-linked SPR1 proteins poorly. Together with our
      data base of 141 examples of in vivo cross-links between SPRs and loricrin, this
      means that both TGase 1 and 3 are required for cross-linking SPR1 proteins in
      epithelia in vivo. Double in vitro cross-linking experiments suggest that
      oligomerization of SPR1 into large polymers can occur only by further TGase 1
      cross-linking of an initial TGase 3 reaction. Accordingly, we propose that TGase
      3 first cross-links loricrin and SPRs together to form small interchain
      oligomers, which are then permanently affixed to the developing CE by further
      cross-linking by the TGase 1 enzyme. This is consistent with the known
      consequences of diminished barrier function in TGase 1 deficiency models.

PMID- 10066785
TI  - Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and
      myogenesis.
AB  - Signaling induced by interaction between the receptor Notch and its ligand Delta
      plays an important role in cell fate determination in vertebrates as well as
      invertebrates. Vertebrate Notch signaling has been investigated using its
      constitutively active form, i.e. the truncated intracellular region which is
      believed to mimic Notch-Delta signaling by interaction with a DNA-binding protein
      RBP-J. However, the molecular mechanism for Notch signaling triggered by ligand
      binding, which leads to inhibition of differentiation, is not clear. We have
      established a myeloma cell line expressing mouse Delta1 on its cell surface which
      can block muscle differentiation by co-culture with C2C12 muscle progenitor
      cells. We showed that Delta-induced Notch signaling stimulated transcriptional
      activation of RBP-J binding motif, containing promoters including the HES1
      promoter. Furthermore, ligand-induced Notch signaling up-regulated HES1 mRNA
      expression within 1 h and subsequently reduced expression of MyoD mRNA. Since
      cycloheximide treatment did not inhibit induction of HES1 mRNA, the HES1 promoter
      appears to be a primary target of activated Notch. In addition, a
      transcriptionally active form of RBP-J, i.e. VP16-RBP-J, inhibited muscle
      differentiation of C2C12 cells by blocking the expression of MyoD protein. These
      results suggest that HES1 induction by the Delta1/Notch signaling is mediated by
      RBP-J and blocks myogenic differentiation of C2C12 cells by subsequent inhibition
      of MyoD expression.

PMID- 10066786
TI  - Cycloheximide-induced T-cell death is mediated by a Fas-associated death domain
      dependent mechanism.
AB  - Cycloheximide (CHX) can contribute to apoptotic processes, either in conjunction
      with another agent (e.g. tumor necrosis factor-alpha) or on its own. However, the
      basis of this CHX-induced apoptosis has not been clearly established. In this
      study, the molecular mechanisms of CHX-induced cell death were examined in two
      different human T-cell lines. In T-cells undergoing CHX-induced apoptosis
      (Jurkat), but not in T-cells resistant to the effects of CHX (CEM C7), caspase-8
      and caspase-3 were activated. However, the Fas ligand was not expressed in Jurkat
      cells either before or after treatment with CHX, suggesting that the activation
      of these caspases does not involve the Fas receptor. To determine whether CHX
      induced apoptosis was mediated by a Fas-associated death domain (FADD)-dependent
      mechanism, a FADD-DN protein was expressed in cells prior to CHX treatment. Its
      expression effectively inhibited CHX-induced cell death, suggesting that CHX
      mediated apoptosis primarily involves a FADD-dependent mechanism. Since CHX
      treatment did not result in the induction of Fas or FasL, and neutralizing anti
      Fas and anti-tumor necrosis factor receptor-1 antibodies did not block CHX
      mediated apoptosis, these results may also indicate that FADD functions in a
      receptor-independent manner. Surprisingly, death effector filaments containing
      FADD and caspase-8 were observed during CHX treatment of Jurkat, Jurkat-FADD-DN,
      and CEM C7 cells, suggesting that their formation may be necessary, but not
      sufficient, for cell death.

PMID- 10066787
TI  - Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum-
      and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel
      convergence point of anti-proliferative and proliferative cell signaling
      pathways.
AB  - The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine
      protein kinase that is transcriptionally regulated in rat mammary tumor cells by
      serum under proliferative conditions or by glucocorticoids that induce a G1 cell
      cycle arrest. Our results establish that the subcellular distribution of Sgk is
      under stringent cell cycle and hormonal control. Sgk is localized to the
      perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in
      cells arrested in G1 by treatment with the synthetic glucocorticoid
      dexamethasone. In serum-stimulated cells, Sgk was transiently hyperphosphorylated
      and resided in the nucleus. Laser scanning cytometry, which monitors Sgk
      localization and DNA content in individual mammary tumor cells of an
      asynchronously growing population, revealed that Sgk actively shuttles between
      the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell
      cycle. In cells synchronously released from the G1/S boundary, Sgk localized to
      the nucleus during progression through S phase. The forced retention of exogenous
      Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the
      nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk),
      suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our
      study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for
      cell cycle progression and represents a novel convergence point of anti
      proliferative and proliferative signaling in mammary tumor cells.

PMID- 10066788
TI  - Anti-apoptotic role of telomerase in pheochromocytoma cells.
AB  - Telomerase is a protein-RNA enzyme complex that adds a six-base DNA sequence
      (TTAGGG) to the ends of chromosomes and thereby prevents their shortening.
      Reduced telomerase activity is associated with cell differentiation and
      accelerated cellular senescence, whereas increased telomerase activity is
      associated with cell transformation and immortalization. Because many types of
      cancer have been associated with reduced apoptosis, whereas cell differentiation
      and senescence have been associated with increased apoptosis, we tested the
      hypothesis that telomerase activity is mechanistically involved in the regulation
      of apoptosis. Levels of telomerase activity in cultured pheochromocytoma cells
      decreased prior to cell death in cells undergoing apoptosis. Treatment of cells
      with the oligodeoxynucleotide TTAGGG or with 3,3'-diethyloxadicarbocyanine,
      agents that inhibit telomerase activity in a concentration-dependent manner,
      significantly enhanced mitochondrial dysfunction and apoptosis induced by
      staurosporine, Fe2+ (an oxidative insult), and amyloid beta-peptide (a cytotoxic
      peptide linked to neuronal apoptosis in Alzheimer's disease). Overexpression of
      Bcl-2 and the caspase inhibitor zVAD-fmk protected cells against apoptosis in the
      presence of telomerase inhibitors, suggesting a site of action of telomerase
      prior to caspase activation and mitochondrial dysfunction. Telomerase activity
      decreased in cells during the process of nerve growth factor-induced
      differentiation, and such differentiated cells exhibited increased sensitivity to
      apoptosis. Our data establish a role for telomerase in suppressing apoptotic
      signaling cascades and suggest a mechanism whereby telomerase may suppress
      cellular senescence and promote tumor formation.

PMID- 10066789
TI  - Intraerythrocytic Plasmodium falciparum expresses a high affinity facilitative
      hexose transporter.
AB  - Asexual stages of Plasmodium falciparum cause severe malaria and are dependent
      upon host glucose for energy. We have identified a glucose transporter of P.
      falciparum (PfHT1) and studied its function and expression during parasite
      development in vitro. PfHT1 is a saturable, sodium-independent, and
      stereospecific transporter, which is inhibited by cytochalasin B, and has a
      relatively high affinity for glucose (Km = 0.48 mM) when expressed in Xenopus
      laevis oocytes. Competition experiments with glucose analogues show that hydroxyl
      groups at positions C-3 and C-4 are important for ligand binding. mRNA levels for
      PfHT1, assessed by the quantitative technique of tandem competitive polymerase
      chain reaction, are highest during the small ring stages of infection and lowest
      in gametocytes. Confocal immunofluorescence microscopy localizes PfHT1 to the
      region of the parasite plasma membrane and not to host structures. These findings
      have implications for development of new drug targets in malaria as well as for
      understanding of the pathophysiology of severe infection. When hypoglycemia
      complicates malaria, modeling studies suggest that the high affinity of PfHT1 is
      likely to increase the relative proportion of glucose taken up by parasites and
      thereby worsen the clinical condition.

PMID- 10066790
TI  - AP-4, a novel protein complex related to clathrin adaptors.
AB  - Here we report the identification and characterization of AP-4, a novel protein
      complex related to the heterotetrameric AP-1, AP-2, and AP-3 adaptors that
      mediate protein sorting in the endocytic and late secretory pathways. The key to
      the identification of this complex was the cloning and sequencing of two widely
      expressed, mammalian cDNAs encoding new homologs of the adaptor beta and sigma
      subunits named beta4 and sigma4, respectively. An antibody to beta4 recognized in
      human cells an approximately 83-kDa polypeptide that exists in both soluble and
      membrane-associated forms. Gel filtration, sedimentation velocity, and
      immunoprecipitation experiments revealed that beta4 is a component of a
      multisubunit complex (AP-4) that also contains the sigma4 polypeptide and two
      additional adaptor subunit homologs named mu4 (mu-ARP2) and epsilon.
      Immunofluorescence analyses showed that AP-4 is associated with the trans-Golgi
      network or an adjacent structure and that this association is sensitive to the
      drug brefeldin A. We propose that, like the related AP-1, AP-2, and AP-3
      complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane
      proteins in mammalian cells.

PMID- 10066791
TI  - The cellular target of histatin 5 on Candida albicans is the energized
      mitochondrion.
AB  - Histatin 5 is a human basic salivary peptide with strong fungicidal properties in
      vitro. To elucidate the mechanism of action, the effect of histatin 5 on the
      viability of Candida albicans cells was studied in relation to its membrane
      perturbing properties. It was found that both the killing activity and the
      membrane perturbing activity, studied by the influx of a DNA-specific marker
      propidium iodide, were inhibited by high salt conditions and by metabolic
      inhibitors, like sodium azide. In addition, exposure to histatin 5 resulted in a
      loss of the mitochondrial transmembrane potential in situ, measured by the
      release of the potential-dependent distributional probe rhodamine 123.
      Localization studies using tetramethylrhodamine isothiocyanate-labeled histatin 5
      or fluorescein isothiocyanate-labeled histatin 5 showed a granular intracellular
      distribution of the peptide, which co-localized with mitotracker orange, a
      permeant mitochondria-specific probe. Like the biological effects, uptake of
      labeled histatin 5 was inhibited by mitochondrial inhibitors and high salt
      conditions. Our data indicate that histatin 5 is internalized, and targets to the
      energized mitochondrion.

PMID- 10066792
TI  - Mutation of a conserved serine residue in a quinolone-resistant type II
      topoisomerase alters the enzyme-DNA and drug interactions.
AB  - A Ser740 --> Trp mutation in yeast topoisomerase II (top2) and of the equivalent
      Ser83 in gyrase results in resistance to quinolones and confers hypersensitivity
      to etoposide (VP-16). We characterized the cleavage complexes induced by the
      top2(S740W) in the human c-myc gene. In addition to resistance to the
      fluoroquinolone CP-115,953, top2(S740W) induced novel DNA cleavage sites in the
      presence of VP-16, azatoxin, amsacrine, and mitoxantrone. Analysis of the VP-16
      sites indicated that the changes in the cleavage pattern were reflected by
      alterations in base preference. C at position -2 and G at position +6 were
      observed for the top2(S740W) in addition to the previously reported C-1 and G+5
      for the wild-type top2. The VP-16-induced top2(S740W) cleavage complexes were
      also more stable. The most stable sites had strong preference for C-1, whereas
      the most reversible sites showed no base preference at positions -1 or -2.
      Different patterns of DNA cleavage were also observed in the absence of drug and
      in the presence of calcium. These results indicate that the Ser740 --> Trp
      mutation alters the DNA recognition of top2, enhances its DNA binding, and
      markedly affects its interactions with inhibitors. Thus, residue 740 of top2
      appears critical for both DNA and drug interactions.

PMID- 10066793
TI  - The topoisomerase-related function gene TRF4 affects cellular sensitivity to the
      antitumor agent camptothecin.
AB  - Camptothecin is an antitumor agent that kills cells by converting DNA
      topoisomerase I into a DNA-damaging poison. Although camptothecin derivatives are
      now being used to treat tumors in a variety of clinical protocols, the cellular
      factors that influence sensitivity to the drug are only beginning to be
      understood. We report here that two genes required for sister chromatid cohesion,
      TRF4 and MCD1/SCC1, are also required to repair camptothecin-mediated damage to
      DNA. The hypersensitivity to camptothecin in the trf4 mutant does not result from
      elevated expression of DNA topoisomerase I. We show that Trf4 is a nuclear
      protein whose expression is cell cycle-regulated at a post-transcriptional level.
      Suppression of camptothecin hypersensitivity in the trf4 mutant by gene
      overexpression resulted in the isolation of three genes: another member of the
      TRF4 gene family, TRF5, and two genes that may influence higher order chromosome
      structure, ZDS1 and ZDS2. We have isolated and sequenced two human TRF4 family
      members, hTRF4-1 and hTRF4-2. The hTRF4-1 gene maps to chromosome 5p15, a region
      of frequent copy number alteration in several tumor types. The evolutionary
      conservation of TRF4 suggests that it may also influence mammalian cell
      sensitivity to camptothecin.

PMID- 10066794
TI  - The functional topography of transmembrane domain 3 of the M1 muscarinic
      acetylcholine receptor, revealed by scanning mutagenesis.
AB  - Alanine-scanning mutagenesis has been applied to residues 100-121 in
      transmembrane domain 3 of the M1 muscarinic acetylcholine receptor. This study
      complements a previous investigation of the triad Asp122-Arg123-Tyr124 (Lu, Z-L.,
      Curtis, C. A., Jones, P. G., Pavia, J., and Hulme, E. C. (1997) Mol. Pharmacol.
      51, 234-241). The results demonstrate the alpha-helical secondary structure of
      the domain and suggest its orientation with respect to the other transmembrane
      domains. The C-terminal part of the helix appears to be largely buried within the
      receptor structure. On its surface, there is a patch of three residues, Val113,
      Leu116, and Ser120, which may form intramolecular contacts that help to stabilize
      the inactive ground state of the receptor. Mutagenic disruption of these
      increased agonist affinity and signaling efficacy. In two cases (L116A and
      S120A), this led to constitutive activation of the receptor. Parallel to the
      helix axis and spanning the whole transmembrane region, a distinct strip of
      residues on one face of transmembrane domain 3 forms intermolecular
      (acetylcholine-receptor, receptor-G protein) or intrareceptor bonds that
      contribute to the activated state. The binding of acetylcholine may destabilize
      the first set of contacts while favoring the formation of the second.

PMID- 10066795
TI  - Identifying the bicyclomycin binding domain through biochemical analysis of
      antibiotic-resistant rho proteins.
AB  - Mutations M219K, S266A, and G337S in transcription termination factor Rho have
      been shown to confer resistance to the antibiotic bicyclomycin (BCM). All three
      His-tagged mutant Rho proteins exhibited similar Km values for ATP; however, the
      Vmax values at infinite ATP concentrations were one-fourth to one-third that for
      the His-tagged wild-type enzyme. BCM inhibition kinetics of poly(C)-dependent
      ATPase activity for the mutant proteins were non-competitive with respect to ATP
      (altering catalytic function but not ATP binding) and showed increased Ki values
      compared with His-tagged wild-type Rho. M219K and G337S exhibited increased
      ratios of poly(U)/poly(C)-stimulated ATPase activity and lower apparent Km values
      for ribo(C)10 in the poly(dC).ribo(C)10-dependent ATPase assay compared with His
      tagged wild-type Rho. The S266A mutation did not show an increased
      poly(U)/poly(C) ATPase activity ratio and maintained approximately the same Km
      for ribo(C)10 in the poly(dC). ribo(C)10-dependent ATPase assay. The kinetic
      studies indicated that M219K and G337S altered the secondary RNA binding domain
      in Rho whereas the S266A mutation did not. Transcription termination assays for
      each mutant showed different patterns of Rho-terminated transcripts. Tyrosine
      substitution of Ser-266 led to BCM sensitivity intimating that an OH (hydroxyl)
      moiety at this position is needed for BCM (binding) inhibition. Our results
      suggest BCM binds to Rho at a site distinct from both the ATP and the primary RNA
      binding domains but close to the secondary RNA-binding (tracking) site and the
      ATP hydrolysis pocket.

PMID- 10066796
TI  - An ankyrin-like protein with transmembrane domains is specifically lost after
      oncogenic transformation of human fibroblasts.
AB  - We have identified a novel transformation-sensitive mRNA, which is present in
      cultured fibroblasts but is lacking in SV40 transformed cells as well as in many
      mesenchymal tumor cell lines. The corresponding gene is located on human
      chromosome 8 in band 8q13. The open reading frame of the mRNA encodes a protein
      of 1119 amino acids forming two distinct domains. The N-terminal domain consists
      of 18 repeats that are related to the cytoskeletal protein ankyrin. The C
      terminal domain contains six putative transmembrane segments that resemble many
      ion channels. This overall structure is reminiscent of TRP-like proteins that
      function as store-operated calcium channels. The novel protein with an Mr of 130
      kDa is expressed at a very low level in human fibroblasts and at a moderate level
      in liposarcoma cells. Overexpression in eukaryotic cells appears to interfere
      with normal growth, suggesting that it might play a direct or indirect role in
      signal transduction and growth control.

PMID- 10066797
TI  - Cell cycle-dependent expression and centrosome localization of a third human
      aurora/Ipl1-related protein kinase, AIK3.
AB  - We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2
      sharing high amino acid sequence identities with Drosophila Aurora and
      Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome
      segregation. In the present study, a third human cDNA (AIK3) highly homologous to
      aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA
      encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal
      kinase domain of AIK3 protein shares high amino acid sequence identities with
      those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2,
      Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of
      AIK3 protein shares little homology with any other Aurora/Ipl1 family members.
      AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently
      deleted or rearranged region in several tumor tissues, by fluorescence in situ
      hybridization, somatic cell hybrid panel, and radiation hybrid cell panel.
      Northern blot analyses revealed that AIK3 expression was limited to testis. The
      expression levels of AIK3 in several cancer cell lines were elevated severalfold
      compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein
      level is low in G1/S, accumulates during G2/M, and reduces after mitosis.
      Immunofluorescence studies using a specific antibody have shown that AIK3 is
      localized to centrosome during mitosis from anaphase to cytokinesis. These
      results suggest that AIK3 may play a role(s) in centrosome function at later
      stages of mitosis.

PMID- 10066798
TI  - pp60(v-src) induction of cyclin D1 requires collaborative interactions between
      the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role
      for cAMP response element-binding protein and activating transcription factor-2
      in pp60(v-src) signaling in breast cancer cells.
AB  - The cyclin D1 gene is overexpressed in breast tumors and encodes a regulatory
      subunit of cyclin-dependent kinases that phosphorylate the retinoblastoma
      protein. pp60(c-src) activity is frequently increased in breast tumors; however,
      the mechanisms governing pp60(c-src) regulation of the cell cycle in breast
      epithelium are poorly understood. In these studies, pp60(v-src) induced cyclin D1
      protein levels and promoter activity (48-fold) in MCF7 cells. Cyclin D1
      associated kinase activity and protein levels were increased in mammary tumors
      from murine mammary tumor virus-pp60(c-src527F) transgenic mice. Optimal
      induction of cyclin D1 by pp60(v-src) involved the extracellular signal-regulated
      kinase, p38, and c-Jun N-terminal kinase members of the mitogen-activated protein
      kinase family. Cyclin D1 promoter activation by pp60(v-src) involved a cAMP
      response element-binding protein (CREB)/activating transcription factor 2 (ATF-2)
      binding site. Dominant negative mutants of CREB and ATF-2 but not c-Jun inhibited
      pp60(v-src) induction of cyclin D1. pp60(v-src) induction of CREB was blocked by
      the p38 inhibitor SB203580 or by mutation of CREB at Ser133. pp60(v-src)
      induction of ATF-2 was abolished by the c-Jun N-terminal kinase inhibitor JNK
      interacting protein-1 or by mutation of ATF-2 at Thr69 and Thr71. CREB and ATF-2,
      which bind to a common pp60(v-src) response element, are transcriptionally
      activated by distinct mitogen-activated protein kinases. Induction of cyclin D1
      activity by pp60(v-src) may contribute to breast tumorigenesis through
      phosphorylation and inactivation of the retinoblastoma protein.

PMID- 10066799
TI  - Photosystem I, an improved model of the stromal subunits PsaC, PsaD, and PsaE.
AB  - An improved electron density map of photosystem I (PSI) calculated at 4-A
      resolution yields a more detailed structural model of the stromal subunits PsaC,
      PsaD, and PsaE than previously reported. The NMR structure of the subunit PsaE of
      PSI from Synechococcus sp. PCC7002 (Falzone, C. J., Kao, Y.-H., Zhao, J., Bryant,
      D. A., and Lecomte, J. T. J. (1994) Biochemistry 33, 6052-6062) has been used as
      a model to interpret the region of the electron density map corresponding to this
      subunit. The spatial orientation with respect to other subunits is described as
      well as the possible interactions between the stromal subunits. A first model of
      PsaD consisting of a four-stranded beta-sheet and an alpha-helix is suggested,
      indicating that this subunit partly shields PsaC from the stromal side. In
      addition to the improvements on the stromal subunits, the structural model of the
      membrane-integral region of PSI is also extended. The current electron density
      map allows the identification of the N and C termini of the subunits PsaA and
      PsaB. The 11-transmembrane alpha-helices of these subunits can now be assigned
      uniquely to the hydrophobic segments identified by hydrophobicity analyses.

PMID- 10066800
TI  - Localization of two phylloquinones, QK and QK', in an improved electron density
      map of photosystem I at 4-A resolution.
AB  - An improved electron density map of photosystem I from Synechococcus elongatus
      calculated at 4-A resolution for the first time reveals a second phylloquinone
      molecule and thereby completes the set of cofactors constituting the electron
      transfer system of this iron-sulfur type photosynthetic reaction center: six
      chlorophyll a, two phylloquinones, and three Fe4S4 clusters. The location of the
      newly identified phylloquinone pair, the individual plane orientations of these
      molecules, and the resulting distances to other cofactors of the electron
      transfer system are discussed and compared with those determined by magnetic
      resonance techniques.

PMID- 10066801
TI  - Deamidation and isoaspartate formation in smeared tau in paired helical
      filaments. Unusual properties of the microtubule-binding domain of tau.
AB  - An extensive loss of a selected population of neurons in Alzheimer's disease is
      closely related to the formation of paired helical filaments (PHFs). The most
      striking characteristic of PHFs upon Western blotting is their smearing.
      According to a previously described protocol (Morishima-Kawashima, M., Hasegawa,
      M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1993) Neuron 10, 1151
      1160), smeared tau was purified, and its peptide map was compared with that of
      soluble (normal) tau. A CNBr fragment from soluble tau (CN5; residues 251-419
      according to the 441-residue isoform) containing the microtubule-binding domain
      migrated at 15 and 18 kDa on SDS-polyacrylamide gel electrophoresis, whereas that
      from smeared tau exhibited two larger, unusually broad bands at approximately 30
      and approximately 45 kDa, presumably representing dimers and trimers of CN5. In
      the peptide map of smeared tau-derived CN5, distinct peaks eluting at unusual
      locations were noted. Amino acid sequence and mass spectrometric analyses
      revealed that these distinct peptides bear isoaspartate at Asn-381 and Asp-387.
      Because no unusual peptides other than aspartyl or isoaspartyl peptide were found
      in the digests of smeared tau-derived CN5, it is likely that site-specific
      deamidation and isoaspartate formation are involved in its dimerization and
      trimerization and thus in PHF formation in vivo.

PMID- 10066802
TI  - Genomic structure and expression of the mouse growth factor receptor related to
      tyrosine kinases (Ryk).
AB  - We report the genomic organization of the mouse orphan receptor related to
      tyrosine kinases (Ryk), a structurally unclassified member of the growth factor
      receptor family. The mouse RYK protein is encoded by 15 exons distributed over a
      minimum of 81 kilobases. Genomic DNA sequences encoding a variant protein
      tyrosine kinase ATP-binding motif characteristic of RYK are unexpectedly found in
      two separate exons. A feature of the gene is an unmethylated CpG island spanning
      exon 1 and flanking sequences, including a TATA box-containing putative promoter
      and single transcription start site. Immunohistochemical examination of RYK
      protein distribution revealed widespread but developmentally regulated
      expression, which was spatially restricted within particular adult organs.
      Quantitative reduction of Southern blotting stringency for the detection of Ryk
      related sequences provided evidence for a retroprocessed mouse pseudogene and a
      more distantly related gene paralogue. Extensive cross-species reactivity of a
      mouse Ryk kinase subdomain probe and the cloning of a Ryk orthologue from
      Caenorhabditis elegans demonstrate that Ryk and its relatives encode widely
      conserved members of a novel receptor tyrosine kinase subfamily.

PMID- 10066803
TI  - Importin beta recognizes parathyroid hormone-related protein with high affinity
      and mediates its nuclear import in the absence of importin alpha.
AB  - Parathyroid hormone-related protein (PTHrP), expressed in a range of tumors, has
      endocrine, autocrine/paracrine, and intracrine actions, some of which relate to
      its ability to localize in the nucleus. Here we show for the first time that
      extracellularly added human PTHrP (amino acids 1-108) can be taken up
      specifically by receptor-expressing UMR106.01 osteogenic sarcoma cells and
      accumulate to quite high levels in the nucleus and nucleolus within 40 min.
      Quantitation of recognition by the nuclear localization sequence (NLS)-binding
      importin subunits indicated that in contrast to proteins containing conventional
      NLSs, PTHrP is recognized exclusively by importin beta and not by importin alpha.
      The sequence of PTHrP responsible for binding was mapped to amino acids 66-94,
      which includes an SV40 large tumor-antigen NLS-like sequence, although sequence
      determinants amino-terminal to this region were also necessary for high affinity
      binding (apparent dissociation constant of approximately 2 nM for importin beta).
      Nuclear import of PTHrP was assessed in vitro using purified components,
      demonstrating that importin beta, together with the GTP-binding protein Ran, was
      able to mediate efficient nuclear accumulation in the absence of importin alpha,
      whereas the addition of nuclear transport factor NTF2 reduced transport. The
      polypeptide ligand PTHrP thus appears to be accumulated in the nucleus/nucleolus
      through a novel, NLS-dependent nuclear import pathway independent of importin
      alpha and perhaps also of NTF2.

PMID- 10066804
TI  - Tat-associated kinase (P-TEFb): a component of transcription preinitiation and
      elongation complexes.
AB  - Human immunodeficiency virus, type 1 (HIV-1) Tat protein activates transcription
      from the HIV-1 long terminal repeat. Tat interacts with TFIIH and Tat-associated
      kinase (a transcription elongation factor P-TEFb) and requires the carboxyl
      terminal domain of the largest subunit of RNA polymerase II (pol II) for
      transactivation. We developed a stepwise RNA pol II walking approach and used
      Western blotting to determine the role of TFIIH and P-TEFb in HIV-1 transcription
      elongation. Our results demonstrate the new findings that P-TEFb is a component
      of the preinitiation complex and travels with the elongating RNA pol II, whereas
      TFIIH is released from the elongation complexes before the trans-activation
      responsive region RNA is synthesized. Our results suggest that TFIIH and P-TEFb
      are involved in the clearance of promoter-proximal pausing of RNA pol II on the
      HIV-1 long terminal repeat at different stages.

PMID- 10066805
TI  - Molecular cloning and biochemical characterization of a novel anthocyanin 5-O
      glucosyltransferase by mRNA differential display for plant forms regarding
      anthocyanin.
AB  - UDP-glucose: anthocyanin 5-O-glucosyltransferase (5-GT) is responsible for the
      modification of anthocyanins to more stable molecules in complexes for co
      pigmentation, supposedly resulting in a purple hue. The cDNA encoding 5-GT was
      isolated by a differential display applied to two different forms of anthocyanin
      production in Perilla frutescens var. crispa. Differential display was carried
      out for mRNA from the leaves of reddish-purple and green forms of P. frutescens,
      resulting in the isolation of five cDNA clones predominantly expressed in the red
      form. The cDNA encoded a polypeptide of 460 amino acids, exhibiting a low
      homology with the sequences of several glucosyltransferases including UDP
      glucose: anthocyanidin 3-O-glucosyltransferase. By using this cDNA as the probe,
      we also isolated a homologous cDNA clone from a petal cDNA library of Verbena
      hybrida. To identify the biochemical function of the encoded proteins, these
      cDNAs were expressed in Saccharomyces cerevisiae cells. The recombinant proteins
      in the yeast extracts catalyzed the conversion of anthocyanidin 3-O-glucosides
      into the corresponding anthocyanidin 3,5-di-O-glucosides using UDP-glucose as a
      cofactor, indicating the identity of the cDNAs encoding 5-GT. Several biochemical
      properties (optimum pH, Km values, and sensitivity to inhibitors) were similar to
      those reported previously for 5-GTs. Southern blot analysis indicated the
      presence of two copies of 5-GT genes in the genome of both red and green forms of
      P. frutescens. The mRNA accumulation of the 5-GT gene was detected in the leaves
      of the red form but not in those of the green form and was induced by
      illumination of light, as observed for other structural genes for anthocyanin
      biosynthesis in P. frutescens.

PMID- 10066806
TI  - The very low density lipoprotein receptor regulates urokinase receptor catabolism
      and breast cancer cell motility in vitro.
AB  - The very low density lipoprotein receptor (VLDLr) binds diverse ligands,
      including urokinase-type plasminogen activator (uPA) and uPA-plasminogen
      activator inhibitor-1 (PAI-1) complex. In this study, we characterized the
      effects of the VLDLr on the internalization, catabolism, and function of the uPA
      receptor (uPAR) in MCF-7 and MDA-MB-435 breast cancer cells. When challenged with
      uPA.PAI-1 complex, MDA-MB-435 cells internalized uPAR; this process was inhibited
      by 80% when the activity of the VLDLr was neutralized with receptor-associated
      protein (RAP). To determine whether internalized uPAR is degraded, we studied the
      catabolism of [35S]methionine-labeled uPAR. In the absence of exogenous agents,
      the uPAR catabolism t(1)/(2) was 8.2 h. uPA.PAI-1 complex accelerated uPAR
      catabolism (t(1)/(2) to 1.8 h), while RAP inhibited uPAR catabolism in the
      presence (t(1)/(2) of 7.8 h) and absence (t(1)/(2) of 16.9 h) of uPA.PAI-1
      complex, demonstrating a critical role for the VLDLr. When MCF-7 cells were
      cultured in RAP, cell surface uPAR levels increased gradually, reaching a new
      steady-state in 3 days. The amount of uPA which accumulated in the medium also
      increased. Culturing in RAP for 3 days increased MCF-7 cell motility by 2.2 +/-
      0.1-fold and by 4.4 +/- 0.3-fold when 1.0 nM uPA was added. The effects of RAP on
      MCF-7 cell motility were entirely abrogated by an antibody which binds uPA and
      prevents uPA binding to uPAR. MCF-7 cells that were cultured in RAP demonstrated
      increased levels of activated mitogen-activated protein kinases. Furthermore, the
      MEK inhibitor, PD098059, decreased the motility of RAP-treated cells without
      affecting control cultures. These studies suggest a model in which the VLDLr
      regulates autocrine uPAR-initiated signaling and thereby regulates cellular
      motility.

PMID- 10066807
TI  - Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene
      expression. Impact of STAT5a gene disruption.
AB  - Stat5b gene disruption leads to an apparent growth hormone (GH) pulse
      insensitivity associated with loss of male-characteristic body growth rates and
      male-specific liver gene expression (Udy, G. B., Towers, R. P., Snell, R. G.,
      Wilkins, R. J., Park, S. H., Ram, P. A., Waxman, D. J., and Davey, H. W. (1997)
      Proc. Natl. Acad. Sci. U. S. A. 94, 7239-7244). In the present study, disruption
      of the mouse Stat5a gene, whose coding sequence is approximately 90% identical to
      the Stat5b gene, resulted in no loss of expression in male mice of several sex
      dependent, GH-regulated liver cytochrome P450 (CYP) enzymes. By contrast, the
      loss of STAT5b feminized the livers of males by decreasing expression of male
      specific CYPs (CYP2D9 and testosterone 16alpha-hydroxylase) while increasing to
      female levels several female-predominant liver CYPs (CYP3A, CYP2B, and
      testosterone 6beta-hydroxylase). Since STAT5a is thus nonessential for these male
      GH responses, STAT5b homodimers, but not STAT5a-STAT5b heterodimers, probably
      mediate the sexually dimorphic effects of male GH pulses on liver CYP expression.
      In female mice, however, disruption of either Stat5a or Stat5b led to striking
      decreases in several liver CYP-catalyzed testosterone hydroxylase activities.
      Stat5a or Stat5b gene disruption also led to the loss of a female-specific, GH
      regulated hepatic CYP2B enzyme. STAT5a, which is much less abundant in liver than
      STAT5b, and STAT5b are therefore both required for constitutive expression in
      female but not male mouse liver of certain GH-regulated CYP steroid hydroxylases,
      suggesting that STAT5 protein heterodimerization is an important determinant of
      the sex-dependent and gene-specific effects that GH has on the liver.

PMID- 10066808
TI  - Activation of Go-proteins by membrane depolarization traced by in situ
      photoaffinity labeling of galphao-proteins with [alpha32P]GTP-azidoanilide.
AB  - Evidence for depolarization-induced activation of G-proteins in membranes of rat
      brain synaptoneurosomes has been previously reported (Cohen-Armon, M., and
      Sokolovsky, M. (1991) J. Biol. Chem. 266, 2595-2605; Cohen-Armon, M., and
      Sokolovsky, M. (1993) J. Biol. Chem. 268, 9824-9838). In the present work we
      identify the activated G-proteins as Go-proteins by tracing their depolarization
      induced in situ photoaffinity labeling with [alpha32P]GTP-azidoanilide (GTPAA).
      Labeled GTPAA was introduced into transiently permeabilized rat brain-stem
      synaptoneurosomes. The resealed synaptoneurosomes, while being UV-irradiated,
      were depolarized. Relative to synaptoneurosomes at resting potential, the
      covalent binding of [alpha32P]GTPAA to Galphao1- and Galphao3-proteins, but not
      to Galphao2- isoforms, was enhanced by 5- to 7-fold in depolarized
      synaptoneurosomes, thereby implying an accelerated exchange of GDP for
      [alpha32P]GTPAA. Their depolarization-induced photoaffinity labeling was
      independent of stimulation of Go-protein-coupled receptors and could be reversed
      by membrane repolarization, thus excluding induction by transmitters release. It
      was, however, dependent on depolarization-induced activation of the voltage-gated
      sodium channels (VGSC), regardless of Na+ current. The alpha subunit of VGSC was
      cross-linked and co-immunoprecipitated with Galphao-proteins in depolarized brain
      stem and cortical synaptoneurosomes. VGSC alpha subunit most efficiently cross
      linked with guanosine 5'-O-2-thiodiphosphate-bound rather than to guanosine 5'-O
      (3-thiotriphosphate)-bound Galphao-proteins in isolated synaptoneurosomal
      membranes. These findings support a possible involvement of VGSC in
      depolarization-induced activation of Go-proteins.

PMID- 10066809
TI  - Prophenoloxidase-activating enzyme of the silkworm, Bombyx mori. Purification,
      characterization, and cDNA cloning.
AB  - Prophenoloxidase-activating enzyme (PPAE) was purified to homogeneity as judged
      by SDS-polyacrylamide gel electrophoresis from larval cuticles of the silkworm,
      Bombyx mori. The purified PPAE preparation was shown to be a mixture of the
      isozymes of PPAE (PPAE-I and PPAE-II), which were eluted at different retention
      times in reversed-phase high performance liquid chromatography. PPAE-I and PPAE
      II seemed to be post translationally modified isozymes and/or allelic variants.
      Both PPAE isozymes were proteins composed of two polypeptides (heavy and light
      chains) that are linked by disulfide linkage(s) and glycosylated serine
      proteases. The results of cDNA cloning, peptide mapping, and amino acid
      sequencing of PPAE revealed that PPAE is synthesized as prepro-PPAE with 441
      amino acid residues and is activated from pro-PPAE by cleavage of a peptide bond
      between Lys152 and Ile153. The homology search showed 36.9% identity of PPAE to
      easter, which is a serine protease involved in dorso-ventral pattern formation in
      the Drosophila embryo, and indicated the presence of two consecutive clip-like
      domains in the light chain. A single copy of the PPAE gene was suggested to be
      present in the silkworm genome. In the fifth instar larvae, PPAE transcripts were
      detected in the integument, hemocytes, and salivary glands but not in the fat
      body or mid gut. A polypeptide cross-reactive to mono-specific anti-PPAE/IgG was
      transiently detected in the extract of eggs between 1 and 3 h after they were
      laid.

PMID- 10066810
TI  - Phosphorylation of CD45 by casein kinase 2. Modulation of activity and mutational
      analysis.
AB  - CD45 is a receptor-type protein-tyrosine phosphatase (PTP) that is required for
      antigen-specific stimulation and proliferation in lymphocytes. This study was
      designed to determine the nature of specific kinases in lymphocytes that
      phosphorylate CD45 and to determine the effect of phosphorylation on CD45 PTP
      activity. A major cytoplasmic lymphocyte kinase that phosphorylated CD45 was
      identified as casein kinase 2 (CK2) by use of an in-gel kinase assay in
      combination with immunoprecipitation, immunodepletion, and specific inhibition.
      Mutational analysis of CK2 consensus sites showed that the target for CK2 was in
      an acidic insert of 19 amino acids in the D2 domain, and Ser to Ala mutations at
      amino acids 965, 968, 969, and 973 abrogated CK2 phosphorylation of CD45. CK2
      phosphorylation increased CD45 activity 3-fold toward phosphorylated myelin basic
      protein, and this increase was reversible by PP2A treatment. Mutation of Ser to
      Glu at the CK2 sites had the same effect as phosphorylation and also tripled the
      Vmax of CD45. CD45 isolated in vivo was highly phosphorylated and could not be
      phosphorylated by CK2 without prior dephosphorylation with phosphatase PP2A. We
      conclude that CK2 is a major lymphocyte kinase that is responsible for in vivo
      phosphorylation of CD45, and phosphorylation at specific CK2 sites regulates CD45
      PTP activity.

PMID- 10066811
TI  - Single copies of subunits d, oligomycin-sensitivity conferring protein, and b are
      present in the Saccharomyces cerevisiae mitochondrial ATP synthase.
AB  - In the mitochondrial ATP synthase (mtATPase) of the yeast Saccharomyces
      cerevisiae, the stoichiometry of subunits d, oligomycin-sensitivity conferring
      protein (OSCP), and b is poorly defined. We have investigated the stoichiometry
      of these subunits by the application of hexahistidine affinity purification
      technology. We have previously demonstrated that intact mtATPase complexes
      incorporating a Hex6-tagged subunit can be isolated via Ni2+-nitrilotriacetic
      acid affinity chromatography (Bateson, M., Devenish, R. J., Nagley, P., and
      Prescott, M. (1996) Anal. Biochem. 238, 14-18). Strains were constructed in which
      Hex6-tagged versions of subunits d, OSCP, and b were coexpressed with the
      corresponding wild-type subunit. This coexpression resulted in a mixed population
      of mtATPase complexes containing untagged wild-type and Hex6-tagged subunits. The
      stoichiometry of each subunit was then assessed by determining whether or not the
      untagged wild-type subunit could be recovered from Ni2+-nitrilotriacetic acid
      purifications as an integral component of those complexes absorbed by virtue of
      the Hex6-tagged subunit. As only the Hex6-tagged subunit was recovered from such
      purifications, we demonstrate that the stoichiometry of subunits d, OSCP, and b
      in yeast is 1 in each case.

PMID- 10066812
TI  - Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic nucleotide
      dependent kinases in vitro and in rat cerebellar slices in situ.
AB  - We have examined cyclic nucleotide-regulated phosphorylation of the neuronal type
      I inositol 1,4,5-trisphosphate (IP3) receptor immunopurified from rat cerebellar
      membranes in vitro and in rat cerebellar slices in situ. The isolated IP3
      receptor protein was phosphorylated by both cAMP- and cGMP-dependent protein
      kinases on two distinct sites as determined by thermolytic phosphopeptide
      mapping, phosphopeptide 1, representing Ser-1589, and phosphopeptide 2,
      representing Ser-1756 in the rat protein (Ferris, C. D., Cameron, A. M., Bredt,
      D. S., Huganir, R. L., and Snyder, S. H. (1991) Biochem. Biophys. Res. Commun.
      175, 192-198). Phosphopeptide maps show that cAMP-dependent protein kinase (PKA)
      labeled both sites with the same time course and same stoichiometry, whereas cGMP
      dependent protein kinase (PKG) phosphorylated Ser-1756 with a higher velocity and
      a higher stoichiometry than Ser-1589. Synthetic decapeptides corresponding to the
      two phosphorylation sites (peptide 1, AARRDSVLAA (Ser-1589), and peptide 2,
      SGRRESLTSF (Ser-1756)) were used to determine kinetic constants for the
      phosphorylation by PKG and PKA, and the catalytic efficiencies were in agreement
      with the results obtained by in vitro phosphorylation of the intact protein. In
      cerebellar slices prelabeled with [32P]orthophosphate, activation of endogenous
      kinases by incubation in the presence of cAMP/cGMP analogues and specific
      inhibitors of PKG and PKA induced in both cases a 3-fold increase in
      phosphorylation of the IP3 receptor. Thermolytic phosphopeptide mapping of in
      situ labeled IP3 receptor by PKA showed labeling on the same sites (Ser-1589 and
      Ser-1756) as in vitro. In contrast to the findings in vitro, PKG preferentially
      phosphorylated Ser-1589 in situ. Because both PKG and the IP3 receptor are
      specifically enriched in cerebellar Purkinje cells, PKG may be an important IP3
      receptor regulator in vivo.

PMID- 10066813
TI  - Repair of large insertion/deletion heterologies in human nuclear extracts is
      directed by a 5' single-strand break and is independent of the mismatch repair
      system.
AB  - The repair of 12-, 27-, 62-, and 216-nucleotide unpaired insertion/deletion
      heterologies has been demonstrated in nuclear extracts of human cells. When
      present in covalently closed circular heteroduplexes or heteroduplexes containing
      a single-strand break 3' to the heterology, such structures are subject to a low
      level repair reaction that occurs with little strand bias. However, the presence
      of a single-strand break 5' to the insertion/deletion heterology greatly
      increases the efficiency of rectification and directs repair to the incised DNA
      strand. Because nick direction of repair is independent of the strand in which a
      particular heterology is placed, the observed strand bias is not due to asymmetry
      imposed on the heteroduplex by the extrahelical DNA segment. Strand-specific
      repair by this system requires ATP and the four dNTPs and is inhibited by
      aphidicolin. Repair is independent of the mismatch repair proteins MSH2, MSH6,
      MLH1, and PMS2 and occurs by a mechanism that is distinct from that of the
      conventional mismatch repair system. Large heterology repair in nuclear extracts
      of human cells is also independent of the XPF gene product, and extracts of
      Chinese hamster ovary cells deficient in the ERCC1 and ERCC4 gene products also
      support the reaction.

PMID- 10066814
TI  - Accelerated transcription of PRPS1 in X-linked overactivity of normal human
      phosphoribosylpyrophosphate synthetase.
AB  - Phosphoribosylpyrophosphate (PRPP) synthetase (PRS) superactivity is an X-linked
      disorder characterized by gout with overproduction of purine nucleotides and uric
      acid. Study of the two X-linked PRS isoforms (PRS1 and PRS2) in cells from
      certain affected individuals has shown selectively increased concentrations of
      structurally normal PRS1 transcript and isoform, suggesting that this form of the
      disorder involves pretranslational dysregulation of PRPS1 expression and might be
      more appropriately termed overactivity of normal PRS. We applied Southern and
      Northern blot analyses and slot blotting of nuclear runoffs to delineate the
      process underlying aberrant PRPS1 expression in fibroblasts and lymphoblasts from
      patients with overactivity of normal PRS. Neither PRPS1 amplification nor altered
      stability or processing of PRS1 mRNA was identified, but PRPS1 transcription was
      increased relative to GAPDH (3- to 4-fold normal in fibroblasts; 1.9- to 2.4-fold
      in lymphoblasts) and PRPS2. Nearly coordinate relative increases in each process
      mediating transfer of genetic information from PRPS1 transcription to maximal
      PRS1 isoform expression in patient fibroblasts further supported the idea that
      accelerated PRPS1 transcription is the major aberration leading to PRS1
      overexpression. In addition, modulated relative increases in PRS activities at
      suboptimal Pi concentration and in rates of PRPP and purine nucleotide synthesis
      in intact patient fibroblasts indicate that despite an intact allosteric
      mechanism of regulation of PRS activity, PRPS1 transcription is a major
      determinant of PRPP and purine synthesis. The genetic basis of disordered PRPS1
      transcription remains unresolved; normal- and patient-derived PRPS1s share
      nucleotide sequence identity at least 850 base pairs 5' to the consensus
      transcription initiation site.

PMID- 10066815
TI  - The SH2 domain-containing inositol 5'-phosphatase (SHIP) recruits the p85 subunit
      of phosphoinositide 3-kinase during FcgammaRIIb1-mediated inhibition of B cell
      receptor signaling.
AB  - Coligation of FcgammaRIIb1 with the B cell receptor (BCR) or FcepsilonRI on mast
      cells inhibits B cell or mast cell activation. Activity of the inositol
      phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes
      the conversion of the phosphoinositide 3-kinase (PI3K) product
      phosphatidylinositol 3,4, 5-trisphosphate (PIP3) into phosphatidylinositol 3,4
      bisphosphate. Recent data demonstrate that coligation of FcgammaRIIb1 with BCR
      inhibits PIP3-dependent Btk (Bruton's tyrosine kinase) activation and the Btk
      dependent generation of inositol trisphosphate that regulates sustained calcium
      influx. In this study, we provide evidence that coligation of FcgammaRIIb1 with
      BCR induces binding of PI3K to SHIP. This interaction is mediated by the binding
      of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C
      terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4
      bisphosphate was only partially reduced during coligation of BCR with
      FcgammaRIIb1 despite a drastic reduction in PIP3. In contrast to the complete
      inhibition of Tec kinase-dependent calcium signaling, activation of the
      serine/threonine kinase Akt was partially preserved during BCR and FcgammaRIIb1
      coligation. The association of PI3K with SHIP may serve to activate PI3K and to
      regulate downstream events such as B cell activation-induced apoptosis.

PMID- 10066816
TI  - Apolipoprotein B stimulates formation of monocyte-macrophage surface-connected
      compartments and mediates uptake of low density lipoprotein-derived liposomes
      into these compartments.
AB  - Much of the cholesterol that accumulates in atherosclerotic plaques is found
      within monocyte-macrophages transforming these cells into "foam cells." Native
      low density lipoprotein (LDL) does not cause foam cell formation. Treatment of
      LDL with cholesterol esterase converts LDL into cholesterol-rich liposomes having
      >90% cholesterol in unesterified form. Similar cholesterol-rich liposomes are
      found in early developing atherosclerotic plaques surrounding foam cells. We now
      show that cholesterol-rich liposomes produced from cholesterol esterase-treated
      LDL can cause human monocyte-macrophage foam cell formation inducing a 3-5-fold
      increase in macrophage cholesterol content of which >60% is esterified. Although
      cytochalasin D inhibited LDL liposome-induced macrophage cholesteryl ester
      accumulation, LDL liposomes did not enter macrophages by phagocytosis. Rather,
      the LDL liposomes induced and entered surface-connected compartments within the
      macrophages, a unique endocytic pathway in these cells that we call patocytosis.
      LDL liposome apoB rather than LDL liposome lipid mediated LDL liposome uptake by
      macrophages. This was shown by the findings that: 1) protease treatment of the
      LDL liposomes prevented macrophage cholesterol accumulation; 2) liposomes
      prepared from LDL lipid extracts did not cause macrophage cholesterol
      accumulation; and 3) purified apoB induced and accumulated within macrophage
      surface-connected compartments. Although apoB mediated the macrophage uptake of
      LDL liposomes, this uptake did not occur through LDL, LDL receptor-related
      protein, or scavenger receptors. Also, LDL liposome uptake was not sensitive to
      treatment of macrophages with trypsin or heparinase. Cholesterol esterase
      mediated transformation of LDL into cholesterol-rich liposomes is an LDL
      modification that: 1) stimulates uptake of LDL cholesterol by apoB-dependent
      endocytosis into surface-connected compartments, and 2) causes human monocyte
      macrophage foam cell formation.

PMID- 10066817
TI  - Transcriptional regulation of the mouse ferritin H gene. Involvement of p300/CBP
      adaptor proteins in FER-1 enhancer activity.
AB  - We previously identified a major enhancer of the mouse ferritin H gene (FER-1)
      that is central to repression of the ferritin H gene by the adenovirus E1A
      oncogene (Tsuji, Y., Akebi, N., Lam, T. K., Nakabeppu, Y., Torti, S. V., and
      Torti, F. M. (1995) Mol. Cell. Biol. 15, 5152-5164). To dissect the molecular
      mechanism of transcriptional regulation of ferritin H, E1A mutants were tested
      for their ability to repress FER-1 enhancer activity using cotransfection with
      ferritin H-chloramphenicol acetyltransferase (CAT) reporter constructs. Here we
      report that p300/CBP transcriptional adaptor proteins are involved in the
      regulation of ferritin H transcription through the FER-1 enhancer element. Thus,
      E1A mutants that failed to bind p300/CBP lost the ability to repress FER-1,
      whereas mutants of E1A that abrogated its interaction with Rb, p107, or p130 were
      fully functional in transcriptional repression. Transfection with E1A did not
      affect endogenous p300/CBP levels, suggesting that repression of FER-1 by E1A is
      not due to repression of p300/CBP synthesis, but to E1A and p300/CBP interaction.
      In addition, we have demonstrated that transfection of a p300 expression plasmid
      significantly activated ferritin H-CAT containing the FER-1 enhancer, but had a
      marginal effect on ferritin H-CAT with FER-1 deleted. Furthermore, both wild-type
      p300 and a p300 mutant that failed to bind E1A but retained an adaptor function
      restored FER-1 enhancer activity repressed by E1A. Sodium butyrate, an inhibitor
      of histone deacetylase, mimicked p300/CBP function in activation of ferritin H
      CAT and elevation of endogenous ferritin H mRNA, suggesting that the histone
      acetyltransferase activity of p300/CBP or its associated proteins may contribute
      to the activation of ferritin H transcription. Recruitment of these broadly
      active transcriptional adaptor proteins for ferritin H synthesis may represent an
      important mechanism by which changes in iron metabolism are coordinated with
      other cellular responses mediated by p300/CBP.

PMID- 10066818
TI  - L-type Ca2+ channels and K+ channels specifically modulate the frequency and
      amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin
      release in GH3 cells.
AB  - GH3 cells showed spontaneous rhythmic oscillations in intracellular calcium
      concentration ([Ca2+]i) and spontaneous prolactin release. The L-type Ca2+
      channel inhibitor nimodipine reduced the frequency of Ca2+ oscillations at lower
      concentrations (100nM-1 microM), whereas at higher concentrations (10 microM), it
      completely abolished them. Ca2+ oscillations persisted following exposure to
      thapsigargin, indicating that inositol 1,4,5-trisphosphate-sensitive
      intracellular Ca2+ stores were not required for spontaneous activity. The K+
      channel inhibitors Ba2+, Cs+, and tetraethylammonium (TEA) had distinct effects
      on different K+ currents, as well as on Ca2+ oscillations and prolactin release.
      Cs+ inhibited the inward rectifier K+ current (KIR) and increased the frequency
      of Ca2+ oscillations. TEA inhibited outward K+ currents activated at voltages
      above -40 mV (grouped within the category of Ca2+ and voltage-activated currents,
      KCa,V) and increased the amplitude of Ca2+ oscillations. Ba2+ inhibited both KIR
      and KCa,V and increased both the amplitude and the frequency of Ca2+
      oscillations. Prolactin release was increased by Ba2+ and Cs+ but not by TEA.
      These results indicate that L-type Ca2+ channels and KIR channels modulate the
      frequency of Ca2+ oscillations and prolactin release, whereas TEA-sensitive KCa,V
      channels modulate the amplitude of Ca2+ oscillations without altering prolactin
      release. Differential regulation of these channels can produce frequency or
      amplitude modulation of calcium signaling that stimulates specific pituitary cell
      functions.

PMID- 10066819
TI  - Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic
      ether reductases to pinoresinol-lariciresinol and isoflavone reductases.
AB  - Pinoresinol-lariciresinol and isoflavone reductase classes are phylogenetically
      related, as is a third, the so-called "isoflavone reductase homologs." This study
      establishes the first known catalytic function for the latter, as being able to
      engender the NADPH-dependent reduction of phenylcoumaran benzylic ethers.
      Accordingly, all three reductase classes are involved in the biosynthesis of
      important and related phenylpropanoid-derived plant defense compounds. In this
      investigation, the phenylcoumaran benzylic ether reductase from the gymnosperm,
      Pinus taeda, was cloned, with the recombinant protein heterologously expressed in
      Escherichia coli. The purified enzyme reduces the benzylic ether functionalities
      of both dehydrodiconiferyl alcohol and dihydrodehydrodiconiferyl alcohol, with a
      higher affinity for the former, as measured by apparent Km and Vmax values and
      observed kinetic 3H-isotope effects. It abstracts the 4R-hydride of the required
      NADPH cofactor in a manner analogous to that of the pinoresinol-lariciresinol
      reductases and isoflavone reductases. A similar catalytic function was observed
      for the corresponding recombinant reductase whose gene was cloned from the
      angiosperm, Populus trichocarpa. Interestingly, both pinoresinol-lariciresinol
      reductases and isoflavone reductases catalyze enantiospecific conversions,
      whereas the phenylcoumaran benzylic ether reductase only shows regiospecific
      discrimination. A possible evolutionary relationship among the three reductase
      classes is proposed, based on the supposition that phenylcoumaran benzylic ether
      reductases represent the progenitors of pinoresinol-lariciresinol and isoflavone
      reductases.

PMID- 10066820
TI  - Inhibition of phosphatidylinositol 3-kinase induces nitric-oxide synthase in
      lipopolysaccharide- or cytokine-stimulated C6 glial cells.
AB  - Nitric oxide (NO) produced by inducible nitric-oxide synthase (iNOS) in different
      cells including brain cells in response to proinflammatory cytokines plays an
      important role in the pathophysiology of demyelinating and neurodegenerative
      diseases. The present study underlines the importance of phosphatidylinositol 3
      kinase (PI 3-kinase) in the expression of iNOS in C6 glial cells and rat primary
      astrocytes. Bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta)
      was unable to induce the expression of iNOS and the production of NO in rat C6
      glial cells. Similarly, wortmannin and LY294002, compounds that inhibit PI 3
      kinase, were also unable to induce the expression of iNOS and the production of
      NO. However, a combination of wortmannin or LY294002 with LPS or IL-1beta induced
      the expression of iNOS and the production of NO in C6 glial cells. Consistent
      with the induction of iNOS, wortmannin also induced iNOS promoter-derived
      chloramphenicol acetyltransferase activity in LPS- or IL-1beta-treated C6 glial
      cells. The expression of iNOS by LPS in C6 glial cells expressing a dominant
      negative mutant of p85alpha, the regulatory subunit of PI 3-kinase, further
      supports the conclusion that inhibition of PI 3-kinase provides a necessary
      signal for the induction of iNOS. Next we examined the effect of wortmannin on
      the activation of mitogen-activated protein (MAP) kinase and nuclear factor NF
      kappaB in LPS- or IL-1beta-stimulated C6 glial cells. In contrast to the
      inability of LPS and IL-1beta alone to induce the expression of iNOS, both LPS
      and IL-1beta individually stimulated MAP kinase activity and induced DNA binding
      and transcriptional activity of NF-kappaB. Wortmannin alone was unable to
      activate MAP kinase and NF-kappaB. Moreover, wortmannin had no effect on LPS- or
      IL-1beta-mediated activation of MAP kinase and NF-kappaB, suggesting that
      wortmannin induced the expression of iNOS in LPS- or IL-1beta-stimulated C6 glial
      cells without modulating the activation of MAP kinase and NF-kappaB. Similar to
      C6 glial cells, wortmannin also stimulated LPS-mediated expression of iNOS and
      production of NO in astrocytes without affecting the LPS-mediated activation of
      NF-kappaB. Taken together, the results from specific chemical inhibitors and
      dominant-negative mutant expression studies demonstrate that apart from the
      activation of NF-kappaB, inhibition of PI 3-kinase is also necessary for the
      expression of iNOS and production of NO.

PMID- 10066821
TI  - Trimming and readdition of glucose to N-linked oligosaccharides determines
      calnexin association of a substrate glycoprotein in living cells.
AB  - To analyze the role of glucose trimming and reglucosylation in the binding of
      substrate proteins to calnexin in the endoplasmic reticulum (ER) of living cells,
      we made use of the thermosensitive vesicular stomatitis virus tsO45 glycoprotein
      (G protein). At nonpermissive temperature the G protein failed to fold completely
      and remained bound to calnexin. When the cells were shifted to permissive
      temperature, complete folding occurred accompanied by glucosidase-mediated
      elimination of calnexin-G protein complexes. If release from calnexin was blocked
      during the temperature shift by inhibiting the glucosidases, folding occurred,
      albeit at a reduced rate. In contrast, when unfolded by a shift from permissive
      to nonpermissive temperature, the G protein was reglucosylated rapidly and became
      capable of rebinding to calnexin. The rate at which calnexin binding occurred
      showed a 20-min delay that was explained by accumulation of the G protein in
      calnexin-free exit sites of the ER. These contained the glucosyltransferase
      responsible for reglucosylation of misfolded glycoproteins but had little or no
      calnexin. After unfolding and reglucosylation, the G proteins moved slowly from
      these structures back to the ER where they reassociated with the chaperone. Taken
      together, these results in live cells fully supported the lectin-only model of
      calnexin function. The ER exit sites emerged as a potentially important location
      for components of the quality control system.

PMID- 10066822
TI  - Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2
      dependent prostaglandin formation via a protein kinase C/mitogen-activated
      protein kinase-dependent pathway.
AB  - Activation of platelets results in shedding of membrane microparticles (MP) with
      potentially bioactive properties. Platelet MP modulate platelet, monocyte, and
      vascular endothelial cell function, both by direct effects of MP arachidonic acid
      (AA) and by its metabolism to bioactive prostanoids. We have previously reported
      that platelet MP induce expression of cyclooxygenase (COX)-2 and prostacyclin
      production in monocytes and endothelial cells. To elucidate further the molecular
      mechanisms that underlie MP-induced up-regulation of COX-2 expression, we
      investigated the response of a human monocytoid (U-937) cell line to platelet MP
      stimulation. In U-937 cells, MP-induced COX-2 expression and eicosanoid formation
      is prevented by pharmacological inhibitors of protein kinase C (PKC), PI 3
      kinase, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated
      kinase, and p38 kinase. Treatment with the PI 3-kinase inhibitors wortmannin and
      LY294002 also blocked MP-induced p42/p44 MAPK, p38, and JNK1 phosphorylation.
      Conversely, platelet MP stimulation of U-937 cells results in direct activation
      of PKC, p42/p44 MAPK, p38 kinase, and c-Jun N-terminal kinase (JNK) as well as
      activation of the transcription factors c-Jun and Elk-1. However, MP failed to
      activate the cAMP response element. Activation of U-937 cells by MP induces
      translocation of classical (PKCbeta), novel (PKCdelta) and atypical (PKCzeta and
      PKClambda) isozymes of PKC from the cytosol to the membrane, with concomitant
      activation of downstream MAPK. While MP-induced activation of p42/p44 MAPK and
      p38 kinase is transient, a sustained activation of JNK1 was observed. Although
      PKC activation is required for MP-induced p42/p44 MAPK, activation of the stress
      kinases p38 and JNK1 was PKC-independent. The fatty acid fraction of the MP
      accounted for these effects, which were mimicked by MP AA. Rather than acting
      directly via nuclear receptors, MP AA activates COX-2-dependent prostaglandin
      production by a PKC/p42/p44 MAPK/p38 kinase-sensitive pathway in which PI 3
      kinase plays a significant role. MP AA also stimulates transcriptional activation
      of COX-2 as well as c-Jun and Elk-1.

PMID- 10066823
TI  - Molecular features underlying the sequential phosphorylation of HS1 protein and
      its association with c-Fgr protein-tyrosine kinase.
AB  - The hematopoietic lineage cell-specific protein HS1 was shown to undergo a
      process of sequential phosphorylation both in vitro and in vivo, which is
      synergistically mediated by Syk and Src family protein-tyrosine kinases and
      essential for B cell antigen receptor-mediated apoptosis. We have now identified
      tyrosine 222 as the HS1 residue phosphorylated by the Src family protein kinases
      c-Fgr and Lyn, and we show that a truncated form of HS1 (HS1-208-401) lacking the
      N-terminal putative DNA binding region and the C-terminal Src homology 3 (SH3)
      domain is still able to undergo all the steps of sequential phosphorylation as
      efficiently as full-length HS1. We also show that a stable association of phospho
      HS1 with c-Fgr through its SH2 domain requires previous autophosphorylation of
      the kinase and is prevented by subsequent phosphorylation of Tyr-222. Kinetic
      studies with HS1 and its truncated forms previously phosphorylated by Syk and
      with a peptide substrate reproducing the sequence around tyrosine 222 support the
      view that efficient phosphorylation of HS1 by Src family protein kinases entirely
      relies on TyrP-SH2 domain interaction with negligible, if any, contribution of
      local specificity determinants. Our data indicate that the proline-rich region of
      HS1 bordered by tyrosyl residues affected by Syk and Src family kinases
      represents a functional domain designed to undergo a process of sequential
      phosphorylation.

PMID- 10066824
TI  - Real-time visualization of the cellular redistribution of G protein-coupled
      receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the
      substance P receptor.
AB  - The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays
      a key role in pain regulation. The SPR desensitizes in the continued presence of
      agonist, presumably via mechanisms that implicate G protein-coupled receptor
      kinases (GRKs) and beta-arrestins. The temporal relationship of these proposed
      biochemical events has never been established for any GPCR other than rhodopsin
      beyond the resolution provided by biochemical assays. We investigate the real
      time activation and desensitization of the human SPR in live HEK293 cells using
      green fluorescent protein conjugates of protein kinase C, GRK2, and beta-arrestin
      2. The translocation of protein kinase C betaII-green fluorescent protein to and
      from the plasma membrane in response to substance P indicates that the human SPR
      becomes activated within seconds of agonist exposure, and the response
      desensitizes within 30 s. This desensitization process coincides with a
      redistribution of GRK2 from the cytosol to the plasma membrane, followed by a
      robust redistribution of beta-arrestin 2 and a profound change in cell morphology
      that occurs after 1 min of SPR stimulation. These data establish a role for GRKs
      and beta-arrestins in homologous desensitization of the SPR and provide the first
      visual and temporal resolution of the sequence of events underlying homologous
      desensitization of a GPCR in living cells.

PMID- 10066825
TI  - Folding and assembly of type X collagen mutants that cause metaphyseal
      chondrodysplasia-type schmid. Evidence for co-assembly of the mutant and wild
      type chains and binding to molecular chaperones.
AB  - Schmid metaphyseal chondrodysplasia results from mutations within the COOH
      terminal globular domain (NC1) of type X collagen, a short chain collagen
      expressed in the hypertrophic region of the growth plate cartilage. Previous in
      vitro studies have proposed that mutations prevent the association of the NC1
      domain of constituent chains of the trimer based upon a lack of formation of a
      trimeric structure that is resistant to dissociation with sodium dodecyl sulfate.
      To examine the effect of mutations on folding and assembly within a cellular
      context, bovine type X cDNAs containing analogous disease causing mutations
      Y598D, N617K, W651R, and wild-type were expressed in semi-permeabilized cells. We
      assessed trimerization of the mutant chains by their ability to form a collagen
      triple helix. Using this approach, we demonstrate that although there is an
      apparent lower efficiency of association of the mutant NC1 domains, they can
      drive the formation of correctly aligned triple helices with the same thermal
      stability as the wild-type collagen. When epitope-tagged mutant and wild-type
      collagen were co-expressed, heterotrimers could be detected by sequential
      immunoprecipitation. Both wild-type and mutant type X chains were found in
      association with the molecular chaperones protein disulfide isomerase and Hsp 47.
      The implications of these findings on the likely mechanism of Schmid metaphyseal
      chondrodysplasia will be discussed.

PMID- 10066826
TI  - Identification of determinants in E2 ubiquitin-conjugating enzymes required for
      hect E3 ubiquitin-protein ligase interaction.
AB  - Members of the hect domain protein family are characterized by sequence
      similarity of their C-terminal regions to the C terminus of E6-AP, an E3
      ubiquitin-protein ligase. An essential intermediate step in E6-AP-dependent
      ubiquitination is the formation of a thioester complex between E6-AP and
      ubiquitin in the presence of distinct E2 ubiquitin-conjugating enzymes including
      human UbcH5, a member of the UBC4/UBC5 subfamily of E2s. Similarly, several hect
      domain proteins, including Saccharomyces cerevisiae RSP5, form ubiquitin
      thioester complexes, indicating that hect domain proteins in general have E3
      activity. We show here, by the use of chimeric E2s generated between UbcH5 and
      other E2s, that a region of UbcH5 encompassing the catalytic site cysteine
      residue is critical for its ability to interact with E6-AP and RSP5. Of
      particular importance is a phenylalanine residue at position 62 of UbcH5 that is
      conserved among the members of the UBC4/UBC5 subfamily but is not present in any
      of the other known E2s, whereas the N-terminal 60 amino acids do not contribute
      significantly to the specificity of these interactions. The conservation of this
      phenylalanine residue throughout evolution underlines the importance of the
      ability to interact with hect domain proteins for the cellular function of
      UBC4/UBC5 subfamily members.

PMID- 10066827
TI  - The tyrosines in the bidentate motif of the env-sea oncoprotein are essential for
      cell transformation and are binding sites for Grb2 and the tyrosine phosphatase
      SHP-2.
AB  - The transforming gene product of the S13 avian erythroblastosis virus, the env
      sea protein, is a member of the hepatocyte growth factor receptor family of
      tyrosine kinases comprising Met, Ron, and Sea. Like all three members of this
      family, the env-sea protein has a so-called bidentate motif (Y557INMAVTY564VNL)
      composed of two tandemly arranged tyrosines in the carboxyl terminus. To
      investigate whether the tyrosine residues in this motif are essential for the env
      sea-mediated transformation, we generated tyrosine to phenylalanine mutations.
      Substitutions of both tyrosine residues resulted in complete loss of the
      transforming activity. In contrast, single mutations at either tyrosine did not
      inhibit transformation of Rat1 cells, and mutation of tyrosine 564 actually
      increased transformation of Rat 1 cells. To define signaling pathways activated
      by the env-sea protein, we looked for protein-protein interactions mediated by
      these tyrosine residues. We show that the bidentate motif is responsible for
      interaction with the adapter protein Grb2, phosphatidylinositol 3-kinase, and the
      tyrosine phosphatase SHP-2. Furthermore, we show that microinjected Src homology
      2 domains from either Grb2 or SHP-2 blocked the transforming activity of the env
      sea protein. Together, these results suggest that the tyrosines within the
      bidentate motif are essential for the env-sea transformation.

PMID- 10066828
TI  - Role of interleukin (IL)-2 receptor beta-chain subdomains and Shc in p38 mitogen
      activated protein (MAP) kinase and p54 MAP kinase (stress-activated protein
      Kinase/c-Jun N-terminal kinase) activation. IL-2-driven proliferation is
      independent of p38 and p54 MAP kinase activation.
AB  - We have shown recently that interleukin (IL)-2 activates the mitogen-activated
      protein (MAP) kinase family members p38 (HOG1/stress-activated protein kinase II)
      and p54 (c-Jun N-terminal kinase/stress-activated protein kinase I). Furthermore,
      the p38 MAP kinase inhibitor SB203580 inhibited IL-2-driven T cell proliferation,
      suggesting that p38 MAP kinase might be involved in mediating proliferative
      signals. In this study, using transfected BA/F3 cell lines, it is shown that both
      the acidic domain and the membrane-proximal serine-rich region of the IL-2Rbeta
      chain are required for p38 and p54 MAP kinase activation and that, as for p42/44
      MAP kinase, this activation requires the Tyr338 residue of the acidic domain, the
      binding site for Shc. It is well established that the acidic domain of the IL
      2Rbeta chain is dispensable for IL-2-driven proliferation, and thus our
      observations suggest that neither p38 nor p54 MAP kinase activation is required
      for IL-2-driven proliferation of BA/F3 cells. In addition, the tetravalent
      guanylhydrazone inhibitor of proinflammatory cytokine production, CNI-1493, can
      block the activation of p54 and p38 MAP kinases by IL-2 but has no effect on IL-2
      driven proliferation of BA/F3 cells, activated primary T cells, or a cytotoxic T
      cell line. Furthermore, our observations provide evidence for the existence of an
      additional, unknown target of the p38 MAP kinase inhibitor SB203580, the
      activation of which is essential for mitogenic signaling by IL-2.

PMID- 10066829
TI  - Bacillus subtilis spore coat.
AB  - In response to starvation, bacilli and clostridia undergo a specialized program
      of development that results in the production of a highly resistant dormant cell
      type known as the spore. A proteinacious shell, called the coat, encases the
      spore and plays a major role in spore survival. The coat is composed of over 25
      polypeptide species, organized into several morphologically distinct layers. The
      mechanisms that guide coat assembly have been largely unknown until recently. We
      now know that proper formation of the coat relies on the genetic program that
      guides the synthesis of spore components during development as well as on
      morphogenetic proteins dedicated to coat assembly. Over 20 structural and
      morphogenetic genes have been cloned. In this review, we consider the
      contributions of the known coat and morphogenetic proteins to coat function and
      assembly. We present a model that describes how morphogenetic proteins direct
      coat assembly to the specific subcellular site of the nascent spore surface and
      how they establish the coat layers. We also discuss the importance of
      posttranslational processing of coat proteins in coat morphogenesis. Finally, we
      review some of the major outstanding questions in the field.

PMID- 10066830
TI  - Metabolic engineering of poly(3-hydroxyalkanoates): from DNA to plastic.
AB  - Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyesters
      that have potential applications as conventional plastics, specifically
      thermoplastic elastomers. A wealth of biological diversity in PHA formation
      exists, with at least 100 different PHA constituents and at least five different
      dedicated PHA biosynthetic pathways. This diversity, in combination with
      classical microbial physiology and modern molecular biology, has now opened up
      this area for genetic and metabolic engineering to develop optimal PHA-producing
      organisms. Commercial processes for PHA production were initially developed by W.
      R. Grace in the 1960s and later developed by Imperial Chemical Industries, Ltd.,
      in the United Kingdom in the 1970s and 1980s. Since the early 1990s, Metabolix
      Inc. and Monsanto have been the driving forces behind the commercial exploitation
      of PHA polymers in the United States. The gram-negative bacterium Ralstonia
      eutropha, formerly known as Alcaligenes eutrophus, has generally been used as the
      production organism of choice, and intracellular accumulation of PHA of over 90%
      of the cell dry weight have been reported. The advent of molecular biological
      techniques and a developing environmental awareness initiated a renewed
      scientific interest in PHAs, and the biosynthetic machinery for PHA metabolism
      has been studied in great detail over the last two decades. Because the structure
      and monomeric composition of PHAs determine the applications for each type of
      polymer, a variety of polymers have been synthesized by cofeeding of various
      substrates or by metabolic engineering of the production organism. Classical
      microbiology and modern molecular bacterial physiology have been brought together
      to decipher the intricacies of PHA metabolism both for production purposes and
      for the unraveling of the natural role of PHAs. This review provides an overview
      of the different PHA biosynthetic systems and their genetic background, followed
      by a detailed summation of how this natural diversity is being used to develop
      commercially attractive, recombinant processes for the large-scale production of
      PHAs.

PMID- 10066832
TI  - Prochlorococcus, a marine photosynthetic prokaryote of global significance.
AB  - The minute photosynthetic prokaryote Prochlorococcus, which was discovered about
      10 years ago, has proven exceptional from several standpoints. Its tiny size (0.5
      to 0.7 microm in diameter) makes it the smallest known photosynthetic organism.
      Its ubiquity within the 40 degrees S to 40 degrees N latitudinal band of oceans
      and its occurrence at high density from the surface down to depths of 200 m make
      it presumably the most abundant photosynthetic organism on Earth. Prochlorococcus
      typically divides once a day in the subsurface layer of oligotrophic areas, where
      it dominates the photosynthetic biomass. It also possesses a remarkable pigment
      complement which includes divinyl derivatives of chlorophyll a (Chl a) and Chl b,
      the so-called Chl a2 and Chl b2, and, in some strains, small amounts of a new
      type of phycoerythrin. Phylogenetically, Prochlorococcus has also proven
      fascinating. Recent studies suggest that it evolved from an ancestral
      cyanobacterium by reducing its cell and genome sizes and by recruiting a protein
      originally synthesized under conditions of iron depletion to build a reduced
      antenna system as a replacement for large phycobilisomes. Environmental
      constraints clearly played a predominant role in Prochlorococcus evolution. Its
      tiny size is an advantage for its adaptation to nutrient-deprived environments.
      Furthermore, genetically distinct ecotypes, with different antenna systems and
      ecophysiological characteristics, are present at depth and in surface waters.
      This vertical species variation has allowed Prochlorococcus to adapt to the
      natural light gradient occurring in the upper layer of oceans. The present review
      critically assesses the basic knowledge acquired about Prochlorococcus both in
      the ocean and in the laboratory.

PMID- 10066833
TI  - Mechanisms of arthropod transmission of plant and animal viruses.
AB  - A majority of the plant-infecting viruses and many of the animal-infecting
      viruses are dependent upon arthropod vectors for transmission between hosts
      and/or as alternative hosts. The viruses have evolved specific associations with
      their vectors, and we are beginning to understand the underlying mechanisms that
      regulate the virus transmission process. A majority of plant viruses are carried
      on the cuticle lining of a vector's mouthparts or foregut. This initially
      appeared to be simple mechanical contamination, but it is now known to be a
      biologically complex interaction between specific virus proteins and as yet
      unidentified vector cuticle-associated compounds. Numerous other plant viruses
      and the majority of animal viruses are carried within the body of the vector.
      These viruses have evolved specific mechanisms to enable them to be transported
      through multiple tissues and to evade vector defenses. In response, vector
      species have evolved so that not all individuals within a species are susceptible
      to virus infection or can serve as a competent vector. Not only are the virus
      components of the transmission process being identified, but also the genetic and
      physiological components of the vectors which determine their ability to be used
      successfully by the virus are being elucidated. The mechanisms of arthropod-virus
      associations are many and complex, but common themes are beginning to emerge
      which may allow the development of novel strategies to ultimately control
      epidemics caused by arthropod-borne viruses.

PMID- 10066834
TI  - Precise packaging of the three genomic segments of the double-stranded-RNA
      bacteriophage phi6.
AB  - Bacteriophage phi6 has a genome of three segments of double-stranded RNA. Each
      virus particle contains one each of the three segments. Packaging is effected by
      the acquisition, in a serially dependent manner, of the plus strands of the
      genomic segments into empty procapsids. The empty procapsids are compressed in
      shape and expand during packaging. The packaging program involves discrete steps
      that are determined by the amount of RNA inside the procapsid. The steps involve
      the exposure and concealment of binding sites on the outer surface of the
      procapsid for the plus strands of the three genomic segments. The plus strand of
      segment S can be packaged alone, while packaging of the plus strand of segment M
      depends upon prior packaging of S. Packaging of the plus strand of L depends upon
      the prior packaging of M. Minus-strand synthesis begins when the particle has a
      full complement of plus strands. Plus-strand synthesis commences upon the
      completion of minus-strand synthesis. All of the reactions of packaging, minus
      strand synthesis, and plus-strand synthesis can be accomplished in vitro with
      isolated procapsids. Live-virus constructions that are in accord with the model
      have been prepared. Mutant virus with changes in the packaging program have been
      isolated and analyzed.

PMID- 10066831
TI  - Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity.
AB  - Cdc42p is an essential GTPase that belongs to the Rho/Rac subfamily of Ras-like
      GTPases. These proteins act as molecular switches by responding to exogenous
      and/or endogenous signals and relaying those signals to activate downstream
      components of a biological pathway. The 11 current members of the Cdc42p family
      display between 75 and 100% amino acid identity and are functional as well as
      structural homologs. Cdc42p transduces signals to the actin cytoskeleton to
      initiate and maintain polarized gorwth and to mitogen-activated protein
      morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42p plays an
      important role in multiple actin-dependent morphogenetic events such as bud
      emergence, mating-projection formation, and pseudohyphal growth. In mammalian
      cells, Cdc42p regulates a variety of actin-dependent events and induces the
      JNK/SAPK protein kinase cascade, which leads to the activation of transcription
      factors within the nucleus. Cdc42p mediates these processes through interactions
      with a myriad of downstream effectors, whose number and regulation we are just
      starting to understand. In addition, Cdc42p has been implicated in a number of
      human diseases through interactions with its regulators and downstream effectors.
      While much is known about Cdc42p structure and functional interactions, little is
      known about the mechanism(s) by which it transduces signals within the cell.
      Future research should focus on this question as well as on the detailed analysis
      of the interactions of Cdc42p with its regulators and downstream effectors.

PMID- 10066835
TI  - Protein targeting to the bacterial cytoplasmic membrane.
AB  - Proteins that perform their activity within the cytoplasmic membrane or outside
      this cell boundary must be targeted to the translocation site prior to their
      insertion and/or translocation. In bacteria, several targeting routes are known;
      the SecB- and the signal recognition particle-dependent pathways are the best
      characterized. Recently, evidence for the existence of a third major route, the
      twin-Arg pathway, was gathered. Proteins that use either one of these three
      different pathways possess special features that enable their specific
      interaction with the components of the targeting routes. Such targeting
      information is often contained in an N-terminal extension, the signal sequence,
      but can also be found within the mature domain of the targeted protein. Once the
      nascent chain starts to emerge from the ribosome, competition for the protein
      between different targeting factors begins. After recognition and binding, the
      targeting factor delivers the protein to the translocation sites at the
      cytoplasmic membrane. Only by means of a specific interaction between the
      targeting component and its receptor is the cargo released for further processing
      and translocation. This mechanism ensures the high-fidelity targeting of
      premembrane and membrane proteins to the translocation site.

PMID- 10066838
TI  - MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS. Instructions To authors* 

PMID- 10066837
TI  - Osmosensing by bacteria: signals and membrane-based sensors.
AB  - Bacteria can survive dramatic osmotic shifts. Osmoregulatory responses mitigate
      the passive adjustments in cell structure and the growth inhibition that may
      ensue. The levels of certain cytoplasmic solutes rise and fall in response to
      increases and decreases, respectively, in extracellular osmolality. Certain
      organic compounds are favored over ions as osmoregulatory solutes, although K+
      fluxes are intrinsic to the osmoregulatory response for at least some organisms.
      Osmosensors must undergo transitions between "off" and "on" conformations in
      response to changes in extracellular water activity (direct osmosensing) or
      resulting changes in cell structure (indirect osmosensing). Those located in the
      cytoplasmic membranes and nucleoids of bacteria are positioned for indirect
      osmosensing. Cytoplasmic membrane-based osmosensors may detect changes in the
      periplasmic and/or cytoplasmic solvent by experiencing changes in preferential
      interactions with particular solvent constituents, cosolvent-induced hydration
      changes, and/or macromolecular crowding. Alternatively, the membrane may act as
      an antenna and osmosensors may detect changes in membrane structure. Cosolvents
      may modulate intrinsic biomembrane strain and/or topologically closed membrane
      systems may experience changes in mechanical strain in response to imposed
      osmotic shifts. The osmosensory mechanisms controlling membrane-based K+
      transporters, transcriptional regulators, osmoprotectant transporters, and
      mechanosensitive channels intrinsic to the cytoplasmic membrane of Escherichia
      coli are under intensive investigation. The osmoprotectant transporter ProP and
      channel MscL act as osmosensors after purification and reconstitution in
      proteoliposomes. Evidence that sensor kinase KdpD receives multiple sensory
      inputs is consistent with the effects of K+ fluxes on nucleoid structure,
      cellular energetics, cytoplasmic ionic strength, and ion composition as well as
      on cytoplasmic osmolality. Thus, osmoregulatory responses accommodate and exploit
      the effects of individual cosolvents on cell structure and function as well as
      the collective contribution of cosolvents to intracellular osmolality.

PMID- 10066839
TI  - Cerebral venous thrombosis: nothing, heparin, or local thrombolysis?

PMID- 10066840
TI  - Randomized, placebo-controlled trial of anticoagulant treatment with low
      molecular-weight heparin for cerebral sinus thrombosis.
AB  - BACKGROUND AND PURPOSE: Treatment of cerebral sinus thrombosis with heparin is
      controversial. We conducted a double-blind, placebo-controlled multicenter trial
      to examine whether anticoagulant treatment improves outcome in patients with
      sinus thrombosis. METHODS: Patients were randomized between body weight-adjusted
      subcutaneous nadroparin (180 anti-factor Xa units/kg per 24 hours) and matching
      placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral
      anticoagulants for patients allocated nadroparin (open part). Patients with
      cerebral hemorrhage caused by sinus thrombosis were also included. RESULTS: Sixty
      patients were enrolled, and none were lost to follow-up. In 1 patient the
      diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%)
      in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a
      poor outcome, defined as death or Barthel Index score of <15 (risk difference, 
      4%; 95% CI, -25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the
      nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome,
      defined as death or Oxford Handicap Score of >/=3 (risk difference, -7%; 95% CI, 
      26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient
      in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in
      the placebo group died from clinically suspected pulmonary embolism. CONCLUSIONS:
      Patients with cerebral sinus thrombosis treated with anticoagulants (low
      molecular-weight heparin followed by oral anticoagulation) had a favorable
      outcome more often than controls, but the difference was not statistically
      significant. Anticoagulation proved to be safe, even in patients with cerebral
      hemorrhage.

PMID- 10066841
TI  - Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin.
AB  - BACKGROUND AND PURPOSE: We chose to evaluate the safety and efficacy of combined
      intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT).
      METHODS: We treated 12 patients with symptoms of 1 to 40 days' duration (eg,
      headache, somnolence, focal deficits, seizures, and nausea and vomiting).
      Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients,
      obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent
      pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and
      contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3
      patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and
      1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose
      of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous
      intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused
      concomitantly. RESULTS: Flow was restored completely in 6 patients and partially
      in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29
      hours (range, 13 to 77 hours). Symptoms improved in these 9 patients
      concomitantly with flow restoration. Flow could not be restored in 3 patients. In
      1 of them, treatment was stopped when little progress had been made, and
      fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic
      worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1
      of these, the hematoma was evacuated. CONCLUSIONS: Our experience with
      intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT
      is encouraging. This therapy should probably be regarded as unsafe in patients
      with obvious hemorrhage. Time to restore flow may be faster than with urokinase
      (an average of 71 hours has been reported for 29 documented patients). Further
      evaluation of rtPA with heparin in CVT is warranted.

PMID- 10066842
TI  - Prevention of stroke in urban China: a community-based intervention trial.
AB  - BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death in
      large cities in China since the 1980s. Meanwhile, the prevalences of hypertension
      and smoking have steadily increased over the last 2 decades. Therefore, a
      community-based intervention trial was initiated in 7 Chinese cities in 1987. The
      overall goal of the study was to evaluate the effectiveness of an intervention
      aimed at reducing multiple risk factors for stroke. The primary study objective
      was to reduce the incidence of stroke by 25% over 3.5 years of intervention.
      METHODS: In May 1987 in each of 7 the cities, 2 geographically separated
      communities with a registered population of about 10 000 each were selected as
      either intervention or control communities. In each community, a cohort
      containing about 2700 subjects (>/=35 years old) free of stroke was sampled, and
      a survey was administered to obtain baseline data and screen the eligible
      subjects for intervention. In each city, a program of treatment for hypertension,
      heart disease, and diabetes was instituted in the intervention cohort (n
      approximately 2700) and health education was provided to the full intervention
      community (n approximately 10 000). A follow-up survey was conducted in 1990.
      Comparisons of intervention and control cohorts in each city were pooled to yield
      a single summary. RESULTS: A total of 18 786 subjects were recruited to the
      intervention cohort and 18 876 to the control cohort from 7 cities. After 3.5
      years, 174 new stroke cases had occurred in the intervention cohort and 253 in
      the control cohort. The 3.5-year cumulative incidence of total stroke was
      significantly lower in the intervention cohort than the control cohort (0.93%
      versus 1.34%; RR=0.69; 95% CI, 0.57 to 0.84). The incidence rates of nonfatal and
      fatal stroke, as well as ischemic and hemorrhagic stroke, were significantly
      lower in the intervention cohort than the control cohort. The prevalence of
      hypertension increased by 4.3% in the intervention cohort and by 7.8% in the
      control cohort. The average systolic and diastolic blood pressures increased more
      in the control cohort than in the intervention cohort. Among hypertensive
      individuals in the intervention cohort, awareness of hypertension increased by
      6.7% and the percentage of hypertensives who regularly took antihypertensive
      medication increased 13.2%. All of these indices became worse in the control
      cohort. The prevalence of heart diseases and diabetes increased significantly in
      the both cohorts (P<0.01). The prevalence of consumption of alcohol increased
      slightly, and that of smoking remained constant in both cohorts. CONCLUSIONS: A
      community-based intervention for stroke reduction is feasible and effective in
      the cities of China. The reduction, due to the intervention, in the incidence of
      stroke in the intervention cohort was statistically significant after 3.5 years
      of intervention. The sharp reduction in the incidence of stroke may be due to the
      interventions having blunted the expected increase in hypertension that
      accompanies aging as well as to better and earlier treatment of hypertension,
      particularly borderline hypertension. Applied health education to all the
      residents of the community may have prevented some normotensive individuals from
      developing hypertension and improved overall health awareness and knowledge.

PMID- 10066843
TI  - Delayed increase in infarct volume after cerebral ischemia: correlations with
      thrombolytic treatment and clinical outcome.
AB  - BACKGROUND AND PURPOSE: Growing experimental evidence indicates that the
      development of cerebral ischemic damage is slower than previously believed. The
      aims of this work were (1) to study the evolution of CT hypoattenuation between
      24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether
      thrombolytic treatment given within 6 hours of stroke affects delayed infarction
      evolution; and (3) to investigate possible correlations between lesion volume
      changes over time and clinical outcome. METHODS: Of 620 patients included in the
      European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients
      whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had
      been randomly divided into 2 groups: 206 patients had been treated with rtPA and
      244 with placebo. CT1 and CT7 were classified according to the location of the
      infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2
      for irregular volumes. The 95% confidence interval of inter- and intrarater
      variability was used to determine whether significant changes in lesion volume
      had occurred between CT1 and CT7. Clinical severity was evaluated by means of the
      Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS:
      Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1
      in all the subgroups of patients and particularly in patients with a subcortical
      lesion. Of the 450 patients studied, 287 (64%) did not show any significant
      change in lesion volume between CT1 and CT7, 143 (32%) showed a significant
      increase and the remaining 20 (4%) a significant decrease. No significant
      correlation was observed between treatment and lesion evolution between CT1 and
      CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery
      were significantly (P<0.05) lower in the subgroup of patients with a significant
      lesion volume increase than in the other 2 groups. CONCLUSIONS: In approximately
      two thirds of patients, infarct size is established 24 to 36 hours after stroke
      onset, whereas in the remaining one third, changes in lesion volume may occur
      later than the first 24 to 36 hours. Many factors may be responsible for delayed
      infarct enlargement and for a lower degree of clinical recovery, both of which
      may occur despite early recombinant tissue plasminogen activator treatment.

PMID- 10066844
TI  - Dose escalation study of the NMDA glycine-site antagonist licostinel in acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Licostinel (ACEA 1021; 5-nitro-6, 7-dichloro-2,3
      quinoxalinedione), a competitive antagonist of glycine at the N-methyl-D
      aspartate (NMDA) receptor, is an effective neuroprotective agent in animal models
      of cerebral ischemia. The purpose of this study was to assess the safety,
      tolerability, and pharmacokinetics of licostinel in patients with acute stroke.
      METHODS: In this 5-center dose escalation trial, patients were enrolled within 48
      hours of an ischemic stroke and treated with ascending doses of a short infusion
      of licostinel or a placebo. Adverse effects were assessed with clinical and
      laboratory measurements, and patient outcome was determined with the National
      Institutes of Health Stroke Scale. RESULTS: Sixty-four patients (44 treated with
      escalating doses of licostinel and 20 who received placebo) were treated. Lower
      doses of licostinel (0.03 to 0.60 mg/kg) were not associated with any significant
      adverse effects. Higher doses of licostinel (1.2 to 3.0 mg/kg) were associated
      with a variety of mild-to-moderate adverse effects including neurological and
      gastrointestinal complaints. No major psychotomimetic effects or significant
      safety concerns occurred. At the higher dose levels, peak plasma concentrations
      of licostinel were substantially higher than those required for neuroprotection
      in animal stroke models. A similar improvement in National Institutes of Health
      Stroke Scale scores over time was seen in both the placebo group and the
      licostinel-treated patients. CONCLUSIONS: A short infusion of licostinel in doses
      up to 3.0 mg/kg is safe and tolerable in acute stroke patients. Licostinel may be
      a safer and better tolerated neuroprotective agent than many of the previously
      evaluated NMDA antagonists.

PMID- 10066845
TI  - Cerebral injury after cardiac surgery: identification of a group at extraordinary
      risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the
      Ischemia Research Education Foundation (IREF) Investigators.
AB  - BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized
      as a serious and costly healthcare problem mandating immediate attention. To
      effect solution, those subgroups of patients at greatest risk must be identified,
      thereby allowing efficient implementation of new clinical strategies. No such
      subgroup has been identified; however, patients undergoing intracardiac surgery
      are thought to be at high risk, but comprehensive data regarding specific risk,
      impact on cost, and discharge disposition are not available. METHODS: We
      prospectively studied 273 patients enrolled from 24 diverse US medical centers,
      who were undergoing intracardiac and coronary artery surgery. Patient data were
      collected using standardized methods and included clinical, historical,
      specialized testing, neurological outcome and autopsy data, and measures of
      resource utilization. Adverse outcomes were defined a priori and determined after
      database closure by a blinded independent panel. Stepwise logistic regression
      models were developed to estimate the relative risks associated with clinical
      history and intraoperative and postoperative events. RESULTS: Adverse cerebral
      outcomes occurred in 16% of patients (43/273), being nearly equally divided
      between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new
      TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at
      hospital discharge and 3 newly diagnosed seizures). Associated resource
      utilization was significantly increased--prolonging median intensive care unit
      stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and
      from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type
      II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after
      hospital discharge was frequently necessary in those with type I outcomes, in
      that only 31% returned home compared with 85% of patients without cerebral
      complications (P<0.001). Significant risk factors for type I outcomes related
      primarily to embolic phenomena, including proximal aortic atherosclerosis,
      intracardiac thrombus, and intermittent clamping of the aorta during surgery. For
      type II outcomes, risk factors again included proximal aortic atherosclerosis, as
      well as a preoperative history of endocarditis, alcohol abuse, perioperative
      dysrhythmia or poorly controlled hypertension, and the development of a low
      output state after cardiopulmonary bypass. CONCLUSIONS: These prospective
      multicenter findings demonstrate that patients undergoing intracardiac surgery
      combined with coronary revascularization are at formidable risk, in that 1 in 6
      will develop cerebral complications that are frequently costly and devastating.
      Thus, new strategies for perioperative management--including technical and
      pharmacological interventions--are now mandated for this subgroup of cardiac
      surgery patients.

PMID- 10066836
TI  - Surface proteins of gram-positive bacteria and mechanisms of their targeting to
      the cell wall envelope.
AB  - The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal
      organelle that is assembled and turned over at designated sites. The cell wall
      also functions as a surface organelle that allows gram-positive pathogens to
      interact with their environment, in particular the tissues of the infected host.
      All of these functions require that surface proteins and enzymes be properly
      targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and
      targeting, have been identified. Cell well sorting is the covalent attachment of
      surface proteins to the peptidoglycan via a C-terminal sorting signal that
      contains a consensus LPXTG sequence. More than 100 proteins that possess cell
      wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein
      A of Staphylococcus aureus, and several internalins of Listeria monocytogenes,
      have been identified. Cell wall targeting involves the noncovalent attachment of
      proteins to the cell surface via specialized binding domains. Several of these
      wall-binding domains appear to interact with secondary wall polymers that are
      associated with the peptidoglycan, for example teichoic acids and
      polysaccharides. Proteins that are targeted to the cell surface include muralytic
      enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples
      for targeted proteins are the surface S-layer proteins of bacilli and clostridia,
      as well as virulence factors required for the pathogenesis of L. monocytogenes
      (internalin B) and Streptococcus pneumoniae (PspA) infections. In this review we
      describe the mechanisms for both sorting and targeting of proteins to the
      envelope of gram-positive bacteria and review the functions of known surface
      proteins.

PMID- 10066846
TI  - Anger expression and incident stroke: prospective evidence from the Kuopio
      ischemic heart disease study.
AB  - BACKGROUND AND PURPOSE: High levels of anger are associated with an increased
      risk of coronary heart disease and hypertension, but little is known about the
      role of anger in stroke risk. METHODS: Anger expression style and risk of
      incident stroke were examined in 2074 men (mean age, 53.0+/-5.2 years) from a
      population-based, longitudinal study of risk factors for ischemic heart disease
      and related outcomes in eastern Finland. Self-reported style of anger expression
      was assessed by questionnaire at baseline. Linkage to the FINMONICA stroke and
      national hospital discharge registers identified 64 first strokes (50 ischemic)
      through 1996. Average follow-up time was 8.3+/-0.9 (mean+/-SD) years. RESULTS:
      Men who reported the highest level of expressed anger were at twice the risk of
      stroke (relative hazard, 2.03; 95% CI, 1.05 to 3.94) of men who reported the
      lowest level of anger, after adjustments for age, resting blood pressure,
      smoking, alcohol consumption, body mass index, low-density and high-density
      lipoprotein cholesterol, fibrinogen, socioeconomic status, history of diabetes,
      and use of antihypertensive medications. Additional analysis showed that these
      associations were evident only in men with a history of ischemic heart disease
      (n=481), among whom high levels of outwardly expressed anger (high anger-out)
      predicted >6-fold increased risk of stroke after risk factor adjustment (relative
      hazard, 6.87; 95% CI, 1.50 to 31.4). Suppressed anger (anger-in) and controlled
      anger (anger-control) were not consistently related to stroke risk. CONCLUSIONS:
      This is the first population-based study to show a significant relationship
      between high levels of expressed anger and incident stroke. Additional research
      is necessary to explore the mechanisms that underlie this association.

PMID- 10066847
TI  - Predictors of brain morphology for the men of the NHLBI twin study.
AB  - BACKGROUND AND PURPOSE: Cross-sectional studies show that cerebrovascular risk
      factors are associated with increased brain atrophy, accumulation of abnormal
      cerebral white matter signals, and clinically silent stroke. We extend these
      findings by examining the relationship between midlife cerebrovascular risk
      factors and later-life differences in brain atrophy, amount of abnormal white
      matter, and stroke on MRI. METHODS: Subjects were the 414 surviving members of
      the prospective National Heart, Lung, and Blood Institute Twin Study, who have
      been examined on 4 separate occasions, spanning the 25 years between 1969-1973
      and 1995-1997. Quantitative measures of brain volume, volume of abnormal white
      matter signal (WMHI), and volume of stroke, when present, were obtained from
      those participating in the fourth examination. RESULTS: The mean+/-SD age of the
      subjects was 47.2+/-3.0 years at initial examination and 72. 5+/-2.9 years at
      final examination. Average blood pressure (BP) levels were normal, although 32%
      of the subjects had received or were currently taking antihypertensive
      medications. As a group, 31% had symptomatic cardiovascular disease, 11% had
      symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular
      disease. Both systolic and diastolic BP levels at initial examination were
      inversely related to brain volume and positively related to WMHI volume. Multiple
      regression analysis identified BP-related measures and vascular risk factors as
      significant predictors of brain and WMHI volumes. In addition, the magnitude of
      orthostatic BP change was significantly associated with WMHI volume. Subjects
      with extensive amounts of WMHI had significantly higher systolic BP at the final
      examination and a higher prevalence of symptomatic cardiovascular and
      cerebrovascular disease, without significant differences in the prevalence of
      hypertension treatment. CONCLUSIONS: Midlife BP measures are significantly
      associated with later-life brain and WMHI volumes and the prevalence of
      symptomatic vascular disease. Since WMHI share cerebrovascular risk factors and
      extensive WMHI are associated with symptomatic vascular disease, extensive WMHI
      may be a subclinical expression of cerebrovascular disease. Careful treatment of
      midlife BP elevations may diminish these later-life brain changes.

PMID- 10066848
TI  - Intracerebral hemorrhage in young people: analysis of risk factors, location,
      causes, and prognosis.
AB  - BACKGROUND AND PURPOSE: The frequency of intracerebral hemorrhages (ICHs) in
      people aged </=40 years has been poorly studied. We investigated the incidence,
      causes, locations, and prognosis of ICH in young patients. METHODS: We evaluated
      all consecutive patients with neuroimaging evidence or pathological confirmation
      of symptomatic ICH. We excluded patients with primary subarachnoid or traumatic
      hemorrhage, past evidence of vascular malformation, or brain tumor. We analyzed
      the risk factors, number, locations, and causes of ICH, and final outcome
      measured by the modified Glasgow Outcome Scale. RESULTS: We retrospectively
      evaluated 200 patients (mean age, 27 years; range, 15 to 40 years). The most
      frequent risk factors were tobacco use (20%), hypocholesterolemia (35%),
      hypertension, (13%), and alcohol use (10%). The locations of ICH were lobar
      (55%), basal ganglia/internal capsule (22%), and others (24%). The most common
      causes of ICH were vascular malformations (49%), including cavernous angioma, and
      hypertension (11%). Cryptogenic ICH was considered in 15%. Other causes included
      cerebral venous thrombosis (5%) and sympathomimetic drug use (4%). The majority
      of patients with ICH that resulted from hypertension were aged >31 years (odds
      ratio, 3.48), and those with ICH that resulted from arteriovenous malformations
      were aged <20 years (odds ratio, 2.80). The final outcome was considered
      favorable in 60%. CONCLUSIONS: ICHs in young people are mainly lobar in location
      and result from vascular malformation. Hypertension causes most cases in which
      the ICH is located in the basal ganglia. Mortality and morbidity in the acute
      phase are low and are related to hypertension as the cause of ICH.

PMID- 10066849
TI  - Brain-specific protein C activation during carotid artery occlusion in humans.
AB  - BACKGROUND AND PURPOSE: Activation of plasma protein C (PC) zymogen by thrombin
      thrombomodulin at the endothelial surface is an important endogenous
      antithrombotic mechanism. It is unknown whether activated protein C (APC) is
      generated in vivo in the cerebrovasculature, because there is only limited
      thrombomodulin expression in human brain vascular endothelium. Therefore, we
      tested the hypothesis that carotid occlusion produces brain-specific PC
      activation. METHODS: Blood samples were simultaneously collected from the
      ipsilateral internal jugular vein and radial artery before and during carotid
      cross-clamping and on "de-occlusion" in 8 awake patients undergoing routine
      carotid endarterectomy. Plasma PC zymogen and circulating APC levels were
      measured using enzyme immunocapture assay and expressed as percent of pooled
      plasma controls. RESULTS: Internal jugular vein APC levels increased 28%
      exclusively during carotid occlusion and then decreased 32% with de-occlusion
      (F=8.1, P<0.005). PC zymogen increased only 5.9% with occlusion (F=6.3, P<0.02),
      consistent with hemoconcentration. There were no changes in radial artery PC or
      APC levels. CONCLUSIONS: These findings demonstrate brain-specific protein C
      activation in humans during carotid occlusion and suggest a protective role for
      endogenous APC generation during cerebrovascular occlusion.

PMID- 10066850
TI  - Increased platelet activation in the chronic phase after cerebral ischemia and
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Enhanced thromboxane (TX) biosynthesis has previously
      been reported in the acute phase after ischemic stroke. We investigated whether
      enhanced urinary excretion of 11-dehydro-TXB2, a noninvasive index of platelet
      activation, was present in the chronic phase after a transient ischemic attack
      (TIA) or stroke, including intracerebral hemorrhage. METHODS: We obtained a
      single urinary sample from 92 patients between 3 and 9 months after onset of
      stroke or TIA. The urinary excretion of the major enzymatic metabolite of TXA2,
      11-dehydro-TXB2, was measured by a previously validated radioimmunoassay. The
      excretion rates were compared with those of 20 control patients with nonvascular
      neurological diseases. RESULTS: Urinary 11-dehydro-TXB2 averaged 294+/-139, 413+/
      419, and 557+/-432 pmol/mmol creatinine for patients with TIA, ischemic stroke,
      and intracerebral hemorrhage, respectively; the values were higher in all
      subgroups (P<0.01) than that in control patients (119+/-66 pmol/mmol). Increased
      11-dehydro-TXB2 excretion was present in 59% of all patients, in 60% (P<0.001) of
      patients with TIA, in 56% (P<0.001) of patients with ischemic stroke, and in 73%
      (P<0.001) of patients with intracerebral hemorrhage. Atrial fibrillation, no
      aspirin use, and severity of symptoms at follow-up contributed independently to
      the level of 11-dehydro-TXB2 excretion in a multiple linear regression analysis.
      CONCLUSIONS: Platelet activation is often present in patients in the chronic
      phase after stroke, including those with intracerebral hemorrhage. Persistent
      platelet activation, which is associated with atrial fibrillation and poor stroke
      outcome, can be substantially suppressed by aspirin treatment.

PMID- 10066851
TI  - Cross-sectional and 4-year longitudinal associations between brachial pulse
      pressure and common carotid intima-media thickness in a general population. The
      EVA study.
AB  - BACKGROUND AND PURPOSE: The cross-sectional and 4-year longitudinal associations
      between brachial pulse pressure (PP) and ultrasound measurements of common
      carotid intima-media thickness (CCA-IMT) were assessed. METHODS: A population of
      957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the
      city of Nantes (western France) and reexamined 4 years later. Longitudinal
      changes in PP and CCA-IMT were computed as the difference between 4-year follow
      up and baseline values. RESULTS: Baseline CCA-IMT and PP were positively
      associated in both age- and sex-adjusted analysis (partial correlation
      coefficient=0.20, P<0.001) and in multivariate analysis adjusted for traditional
      cardiovascular risk factors and mean blood pressure (partial correlation
      coefficient=0.18, P<0.001). In longitudinal analysis, baseline PP was associated
      with the change in 4-year CCA-IMT (partial correlation coefficient=0.11,
      P<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP
      (partial correlation coefficient=0.10, 0.001<P<0.01). No association between mean
      blood pressure and CCA-IMT was observed once PP was taken into account, in either
      cross-sectional or longitudinal analyses (partial correlation coefficients ranged
      from 0.00 to 0.03). Similar patterns of results were observed in hypertensive,
      nonhypertensive, and antihypertensive-treated and -nontreated subjects.
      CONCLUSIONS: This longitudinal study of a large population of relatively aged
      subjects suggests that elevated levels of PP are associated with the progression
      of CCA-IMT, and increased CCA-IMT is associated with PP widening. The nature of
      these relationships and whether atherosclerosis progression over time is involved
      or not in these associations merit further investigations.

PMID- 10066852
TI  - Neuropsychological impairment correlates with hypoperfusion and hypometabolism
      but not with severity of white matter lesions on MRI in patients with cerebral
      microangiopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral microangiopathy, indicated on MRI by lacunar
      infarctions (LI) and deep white matter lesions (DWML), is said to lead to
      vascular dementia. METHODS: Fifty-seven patients with proven cerebral
      microangiopathy were assessed for changes in regional cerebral blood flow (rCBF)
      and glucose metabolism (rMRGlu) and compared with 19 age-matched controls. The
      findings were correlated with results of extensive neuropsychological testing, as
      well as with MRI findings. A special head holder ensured reproducibility of
      positioning during rCBF (single-photon emission CT [SPECT]), rMRGlu (positron
      emission tomography [PET]), and MR imaging. White matter and cortex were
      quantified with regions of interest defined on MRI and superimposed to
      corresponding PET/SPECT slices. LI and DWML were graded by number and extent.
      RESULTS: Even with severe DWML and multiple LI, rCBF and rMRGlu values were not
      reduced. ANOVAs identified brain atrophy and neuropsychological deficits as the
      main determinants for reduced rCBF and rMRGlu values in both cortex and white
      matter. Neuropsychological deficits correlated well with decreased rCBF and
      rMRGlu, whereas MRI patterns such as LI and DWML did not. Factor analysis
      revealed no correlation of LI and DWML with rCBF, rMRGlu, atrophy, and
      neuropsychological deficits, showing instead positive correlations between rCBF,
      rMRGlu, and neuropsychological performance and negative correlations of the
      latter 3 with brain atrophy. CONCLUSIONS: From these data, we conclude that LI
      and DWML are epiphenomena that may morphologically characterize cerebral
      microangiopathy but do not in themselves indicate cognitive impairment. Dementia
      or neuropsychological deficits, by contrast, are reflected exclusively by
      functional imaging parameters (rCBF, rMRGlu) and cerebral atrophy.

PMID- 10066853
TI  - Psychological well-being 3 years after severe stroke.
AB  - BACKGROUND AND PURPOSE: Stroke often has a very negative influence on the
      victims' perception of their life situation. The aim of this study was therefore
      to assess the subjects' long-term psychological well-being and to explore
      associations between subject characteristics, impairments, disabilities, and
      psychological well-being. METHODS: Of 100 subjects rehabilitated at a specialized
      geriatric stroke ward after the acute phase, 47 survivors were assessed in their
      homes 3 years after discharge and interviewed regarding their psychological well
      being with the Philadelphia Geriatric Center Morale Scale (PGCMS). RESULTS: Sixty
      four percent of the subjects were classified as having high scores for
      psychological well-being or fell within the middle range. In a cluster analysis,
      depression was shown to have the strongest association with the subjects' PGCMS
      scores. Variables including the subjects' social situation and functions as well
      as age, gender, ability to communicate, and need for help showed a much weaker
      association with the PGCMS. CONCLUSIONS: More than half of the stroke subjects
      were classified as having levels of psychological well-being that were good or
      fairly good. The strong association between PGCMS scores and depression indicates
      the importance of detecting and treating depression and of following up initiated
      therapy after stroke.

PMID- 10066854
TI  - Randomized, controlled trial to evaluate increased intensity of physiotherapy
      treatment of arm function after stroke.
AB  - BACKGROUND AND PURPOSE: Many patients have impaired arm function after stroke,
      for which they receive physiotherapy. The aim of the study was to determine
      whether increasing the amount of physiotherapy early after stroke improved the
      recovery of arm function and to compare the effects of this therapy when
      administered by a qualified therapist or a trained, supervised assistant. The
      physiotherapy followed a typical British approach, which is Bobath derived. Ten
      hours of additional therapy were given over a 5-week period. METHODS: The study
      design was a single-blind, randomized, controlled trial. Stroke patients were
      recruited from those admitted to the hospital in the 5 weeks after stroke. They
      were randomly allocated to routine physiotherapy, additional treatment by a
      qualified physiotherapist, or additional treatment by a physiotherapy assistant.
      Outcome was assessed after 5 weeks of treatment and at 3 and 6 months after
      stroke on measures of arm function and of independence in activities of daily
      living. RESULTS: There were 282 patients recruited to the study. The median
      initial Barthel score was 6.5, and the median age of the patients was 73 years.
      The median initial Rivermead Motor Assessment Arm score was 1. There were no
      significant differences between the groups at randomization or on any of the
      outcome measures. Only half of the patients allocated to the 2 additional-therapy
      groups completed the program. CONCLUSIONS: This increase in the amount of
      physiotherapy for arm impairment with a typical British approach given early
      after stroke did not significantly improve the recovery of arm function in the
      patients studied. A number of other studies of interventions aimed at
      rehabilitation of arm function have reported positive results. Such findings may
      have been due to the content of these interventions, to the greater intensity of
      the interventions, or to the selection of patients to whom the treatments were
      applied.

PMID- 10066855
TI  - A clinical guide to assess the role of lower limb extensor overactivity in
      hemiplegic gait disorders.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess the role of knee and
      ankle extensor overactivity in the hemiplegic gait observed in stroke victims and
      to propose a clinical guide for selecting patients before treatment of a supposed
      disabling spasticity. METHODS: A standardized physical examination procedure was
      performed in 135 consecutive stroke patients. All patients were able to walk
      without human assistance. The period after stroke ranged from 3 to 24 months
      (mean, 11.5+/-7.25 months). Spasticity was evaluated with the stroke victim in
      sitting position and during walking. Overactivity of the quadriceps was
      considered disabling when inducing inability to flex the knee during the swing
      phase despite adequate control of knee flexion in sitting and standing positions;
      overactivity of the triceps surae was considered to be disabling when heel strike
      was not possible despite good control of the ankle flexion in sitting position;
      triceps retraction was also considered. RESULTS: Disabling overactivity was
      observed in 56 (41.5%) patients: 11 times for the quadriceps femoris, 21 times
      for the triceps surae, and 21 times for both muscles. It was considered to be the
      main disorder impairing gait among only 16 (12%) patients: 9 for the quadriceps
      alone, 3 for the triceps alone, and 4 for both. Sitting spasticity of the lower
      limb was not predictive of disabling overactivity during walking. CONCLUSIONS:
      Extensor muscle overactivity is one of the components of gait disorders in stroke
      patients. The difficulty in assessing spasticity and its real causal effect in
      gait disturbances are discussed. A clinical guide is proposed.

PMID- 10066856
TI  - Effects of constraint-induced movement therapy on patients with chronic motor
      deficits after stroke: a replication.
AB  - BACKGROUND AND PURPOSE: Constraint-induced movement therapy (CI therapy) has
      previously been shown to produce large improvements in actual amount of use of a
      more affected upper extremity in the "real-world" environment in patients with
      chronic stroke (ie, >1 year after the event). This work was carried out in an
      American laboratory. Our aim was to determine whether these results could be
      replicated in another laboratory located in Germany, operating within the context
      of a healthcare system in which administration of conventional types of physical
      therapy is generally more extensive than in the United States. METHODS: Fifteen
      chronic stroke patients were given CI therapy, involving restriction of movement
      of the intact upper extremity by placing it in a sling for 90% of waking hours
      for 12 days and training (by shaping) of the more affected extremity for 7 hours
      on the 8 weekdays during that period. RESULTS: Patients showed a significant and
      very large degree of improvement from before to after treatment on a laboratory
      motor test and on a test assessing amount of use of the affected extremity in
      activities of daily living in the life setting (effect sizes, 0.9 and 2.2,
      respectively), with no decrement in performance at 6-month follow-up. During a
      pretreatment control test-retest interval, there were no significant changes on
      these tests. CONCLUSIONS: Results replicate in Germany the findings with CI
      therapy in an American laboratory, suggesting that the intervention has general
      applicability.

PMID- 10066857
TI  - Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the
      possibility of obtaining prognostic indications in patients with internal carotid
      occlusion on the basis of intracranial hemodynamic status, presence of previous
      symptoms of cerebrovascular failure, and baseline characteristics. METHODS:
      Cerebral hemodynamics were studied with transcranial Doppler ultrasonography.
      Cerebrovascular reactivity to apnea was calculated by means of the breath-holding
      index (BHI) in the middle cerebral arteries. Sixty-five patients with internal
      carotid artery occlusion were followed-up prospectively (median, 24 months), 23
      patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack
      and 22 with stroke). RESULTS: During the follow-up period, 11 symptomatic
      patients and 1 asymptomatic patient had another ischemic event ipsilateral to
      carotid occlusion. Among factors considered, only lower BHI values in the middle
      cerebral arteries ipsilateral to carotid occlusion and older age were
      significantly associated with the risk of developing symptoms (P=0.002 and
      P=0.003, respectively; Cox regression multivariate analysis). Based on our data,
      a cut point of the BHI value for distinguishing between pathological and normal
      cerebrovascular reactivity was determined to be 0.69. All patients except one,
      who developed TIA or stroke during the follow-up period, had BHI values
      ipsilateral to carotid occlusion of <0.69. CONCLUSIONS: These data suggest that
      impaired cerebrovascular reactivity is predictive for cerebral ischemic events in
      patients with carotid occlusion.

PMID- 10066858
TI  - Diffusion- and perfusion-weighted imaging in vasospasm after subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Better measures of cerebral tissue perfusion and earlier
      detection of ischemic injury are needed to guide therapy in subarachnoid
      hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia
      and early ischemic injury with combined diffusion-weighted (DW) and
      hemodynamically weighted (HW) MRI in patients with vasospasm after SAH. METHODS:
      Combined DW and HW imaging was used to study 6 patients with clinical and
      angiographic vasospasm, 1 patient without clinical signs of vasospasm but with
      severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis
      of the passage of an intravenous contrast bolus through brain was used to
      construct multislice maps of relative cerebral blood volume (rCBV), relative
      cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize
      that large HW imaging (HWI) abnormalities would be present in treated patients at
      the time they develop neurological deficit due to vasospasm without matching DW
      imaging (DWI) abnormalities. RESULTS: Small, sometimes multiple, ischemic lesions
      on DWI were seen encircled by a large area of decreased rCBF and increased tMTT
      in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent.
      MRI hemodynamic abnormalities occurred in regions supplied by vessels with
      angiographic vasospasm or in their watershed territories. All patients with
      neurological deficit showed an area of abnormal tMTT much larger than the area of
      DWI abnormality. MRI images were normal in the asymptomatic patient with
      angiographic vasospasm and the patient with normal angiogram and no clinical
      signs of vasospasm. CONCLUSIONS: We conclude that DW/HW MRI in symptomatic
      vasospasm can detect widespread changes in tissue hemodynamics that encircle
      early foci of ischemic injury. With additional study, the technique could become
      a useful tool in the clinical management of patients with SAH.

PMID- 10066859
TI  - CT angiography and Doppler sonography for emergency assessment in acute basilar
      artery ischemia.
AB  - BACKGROUND AND PURPOSE: Both Doppler sonography (DS) and spiral CT angiography
      (CTA) are noninvasive vascular assessment tools with a high potential for
      application in acute cerebral ischemia. The usefulness of CTA for vascular
      diagnosis in acute basilar artery (BA) ischemia has not yet been studied.
      METHODS: We prospectively studied 19 patients (mean+/-SD age, 58+/-11 years) with
      clinically suspected acute BA occlusion by DS and CTA. Prior extracranial and
      transcranial DS was performed in all but 1 patient, with DS 4 hours after CTA. In
      6 of 19 patients, we performed digital subtraction angiography. RESULTS: CTA was
      diagnostic in all but 1 patient. CTA revealed complete BA occlusion in 9 patients
      and incomplete BA occlusion with some residual flow in 2 patients. A patent BA
      was shown in 7 patients. Because of severe BA calcification, CTA results were
      inconclusive in 1 patient. DS was diagnostic in only 7 of 19 patients, indicating
      certain BA occlusion in 3 patients and BA patency in 4 patients. In an additional
      9 patients, the results of DS were inconclusive. DS was false-negative in 2
      patients with distal BA occlusion shown by CTA and digital subtraction
      angiography. In 1 patient with DS performed after CTA, recanalization was
      demonstrated. In addition to the diagnosis or exclusion of BA occlusion, CTA
      provided information on the exact site and length of BA occlusion and collateral
      pathways. In our series, CTA results prompted indication for intra-arterial
      thrombolysis in 5 patients. CONCLUSIONS: CTA was superior to DS in the assessment
      of BA patency in patients with the syndrome of acute BA ischemia in terms of
      feasibility and conclusiveness, particularly in cases with distal BA occlusion.
      Our study confirmed the usefulness of combined extracranial and transcranial DS
      in the diagnosis and exclusion of proximal BA occlusion.

PMID- 10066860
TI  - beta-amyloid load is not influenced by the severity of cardiovascular disease in
      aged and demented patients.
AB  - BACKGROUND AND PURPOSE: This study was conducted to analyze the association
      between reported risk factors for Alzheimer's disease, apolipoprotein E epsilon4
      allele, and cardiovascular disease and neuropathological changes essential for
      the diagnosis of Alzheimer's disease. METHODS: Our data are based on clinical and
      postmortem evaluations of a cohort of nondemented (n=118) and demented (n=107)
      individuals. A cardiovascular index was calculated at autopsy to estimate the
      extent of cardiovascular disease. Neuropathological lesions such as
      senile/neuritic plaques, neurofibrillary tangles, beta-amyloid load, cerebral
      amyloid angiopathy, and the load of paired helical filaments were determined.
      RESULTS: The aforementioned neuropathological lesions did not show any positive
      significant correlation with cardiovascular index. In contrast, the extent of
      Alzheimer's lesions was significantly higher in those nondemented and demented
      patients carrying the apolipoprotein E epsilon4 allele than in those without this
      allele. CONCLUSIONS: Our results demonstrate that the apolipoprotein E epsilon4
      allele, but not cardiovascular disease, indeed influences the extent of
      Alzheimer's lesions seen in the brain tissue of demented patients as well as
      asymptomatic controls.

PMID- 10066861
TI  - Age and stimulus dependency of visually evoked cerebral blood flow responses.
AB  - BACKGROUND AND PURPOSE: During visual stimulation, the increased metabolic demand
      is coupled with an increase of cerebral blood flow velocity (pCBFV) in the
      posterior cerebral artery (PCA). Investigation of the visually evoked flow
      responses (VEFR, expressed as percentage of increase from baseline pCBFV values)
      was suggested for different conditions of vasoneuronal disorders in the absence
      of any systematic investigation in healthy subjects. METHODS: We investigated
      VEFRs from both PCAs to various increasingly complex paradigms (diffuse light,
      alternating checkerboard patterns, and a color video movie stimulation; 5, 10,
      20, and 30-second intervals) in 60 healthy volunteers (mean age, 41.5+/-14.9
      years; range, 24 to 80 years; 28 male, 32 female) at different recording sites
      (P1 versus P2 segments of PCAs). RESULTS: With increasing complexity of
      stimulation, the VEFRs increased significantly (24.3+/-10.3%, 28.5+/-13.5%, and
      43.4+/-10.7%, respectively). Twenty-second stimulation intervals yielded maximal
      responses (41.5+/-13.2%) compared with 5-, 10-, and 30-second intervals (22.6+/
      14.1%, P=0.001; 34.4+/-11.7%, P=0.0042; and 35.5+/-9.9%, P=0.0032, respectively).
      Significantly higher responses were gained from P2 segments than from P1 segments
      (42.7+/-7.2% versus 28.2+/-7.1%). Although VEFRs tended to decrease in amplitude
      with age (mean, 41. 7+/-10.5% [20 to 40 years], 35+/-9.2% [40 to 60 years], and
      33.9+/-8.6% [60 to 80 years]); without significant sex-related differences, only
      the percentage decrement of the pulsatility indices during stimulation were
      significant (mean, 24+/-10.7% [20 to 40 years], 20+/-7.3% [40 to 60 years], and
      13+/-11.2% [60 to 80 years]). CONCLUSIONS: For optimal stimulus conditions for
      maximum VEFRs, a colored video stimulation of 20-second intervals should be used
      to combine responses not only from the primary visual projection fields (V1 and
      V2) but also from temporal lobe areas (V3 through V5) often supplied by the PCA.

PMID- 10066862
TI  - Thrombolysis with tissue plasminogen activator alters adhesion molecule
      expression in the ischemic rat brain.
AB  - BACKGROUND AND PURPOSE: We tested the hypothesis that treatment of embolic stroke
      with recombinant human tissue plasminogen activator (rhtPA) alters cerebral
      expression of adhesion molecules. METHODS: Male Wistar rats were subjected to
      middle cerebral artery occlusion by a single fibrin-rich clot. P-selectin, E
      selectin, and intercellular adhesion molecule-1 (ICAM-1) immunoreactivity was
      measured at 6 or 24 hours after embolic stroke in control rats and in rats
      treated with rhtPA at 1 or 4 hours after stroke. To examine the therapeutic
      efficacy of combined rhtPA and anti-ICAM-1 antibody treatment at 4 hours after
      embolization, ischemic lesion volumes were measured in rats treated with rhtPA
      alone, rats treated with rhtPA and anti-ICAM-1 antibody, and nontreated rats.
      RESULTS: Administration of rhtPA at 1 hour after embolization resulted in a
      significant reduction of adhesion molecule vascular immunoreactivity after
      embolization in the ipsilateral hemisphere compared with corresponding control
      rats. However, when rhtPA was administered to rats at 4 hours after embolization,
      significant increases of adhesion molecule immunoreactivity in the ipsilateral
      hemisphere were detected. A significant increase of ICAM-1 immunoreactivity was
      also detected in the contralateral hemisphere at 24 hours after ischemia. A
      significant reduction in lesion volume was found in rats treated with the
      combination of rhtPA and anti-ICAM-1 antibody compared with rats treated only
      with rhtPA. CONCLUSIONS: The present study suggests that the time of initiation
      of thrombolytic therapy alters vascular immunoreactivity of inflammatory adhesion
      molecules in the ischemic brain and that therapeutic benefit can be obtained by
      combining rhtPA and anti-ICAM-1 antibody treatment 4 hours after stroke.

PMID- 10066863
TI  - Estrogen provides neuroprotection in transient forebrain ischemia through
      perfusion-independent mechanisms in rats.
AB  - BACKGROUND AND PURPOSE: Estrogen-related neuroprotection in association with
      animal models of transient forebrain and focal ischemia has been documented in
      several recent reports. Some of those studies indicated that part of that benefit
      was a function of improved intraischemic vasodilating capacity. In the present
      study we examined whether chronic estrogen depletion and repletion affected
      ischemic neuropathology through perfusion-independent mechanisms. METHODS:
      Normal, ovariectomized (OVX), and OVX female rats treated with 17beta-estradiol
      (E2) were subjected to 30 minutes of transient forebrain ischemia (right common
      carotid occlusion plus hemorrhagic hypotension) and reperfusion. Neurological
      function and brain histopathology were assessed over the 72-hour recovery period.
      In all rats, preischemic and intraischemic cortical cerebral blood flow (CBF)
      levels were monitored with laser-Doppler flowmetry. In additional rats, CBF
      changes in the striatum and hippocampus were also monitored with laser-Doppler
      flowmetry probes and radiolabeled microspheres. In each experiment, the level of
      ischemia was targeted to a 75% to 80% reduction in cortical CBF. RESULTS: The
      similarity in ischemic severity among groups was supported by measurements of
      comparable patterns of electroencephalographic power changes during the ischemic
      period. Compared with normal females, OVX rats showed diminished neurological
      outcomes and more severe histopathology in the hippocampus and striatum. Two-week
      treatment of OVX rats with E2 was accompanied by postischemic neuropathological
      changes similar to those seen in normal females. Intraischemic CBF reductions in
      the hippocampus and striatum were similar in all groups (to 35% to 50% of the
      preischemic value) but significantly less than the cortical CBF reductions.
      CONCLUSIONS: These findings indicate that estrogen provides ischemic
      neuroprotection through mechanisms unrelated to improvement of intraischemic
      cerebral perfusion.

PMID- 10066864
TI  - Blockade and reversal of endothelin-induced constriction in pial arteries from
      human brain.
AB  - BACKGROUND AND PURPOSE: Substantial evidence now implicates endothelin (ET) in
      the pathophysiology of cerebrovascular disorders such as the delayed vasospasm
      associated with subarachnoid hemorrhage and ischemic stroke. We investigated the
      ET receptor subtypes mediating vasoconstriction in human pial arteries. METHODS:
      ET receptors on human pial and intracerebral arteries were visualized with the
      use of autoradiography, and the subtypes mediating vasoconstriction were
      identified by means of wire myography. RESULTS: ET-1 was more potent than ET-3 as
      a vasoconstrictor, indicating an ETA-mediated effect. Similarly, the selective
      ETB agonist sarafotoxin S6c had no effect on contractile action at concentrations
      up to 30 nmol/L. The nonpeptide ETA receptor antagonist PD156707 (3 to 30 nmol/L)
      caused a parallel rightward shift of the ET-1-induced response, yielding a pA2 of
      9.2. Consistent with these results, PD156707 (30 nmol/L) fully reversed an
      established constriction in pial arteries induced by 1 nmol/L ET-1, while the
      selective ETB receptor antagonist BQ788 (1 micromol/L) had little effect. The
      calcium channel blocker nimodipine (0.3 to 3 micromol/L) significantly attenuated
      the maximum response to ET-1 in a concentration-dependent manner without changing
      potency. In agreement with the functional data, specific binding of
      [125I]PD151242 to ETA receptors was localized to the smooth muscle layer of pial
      and intracerebral blood vessels. In contrast, little or no [125I]BQ3020 binding
      to ETB receptors was detected. CONCLUSIONS: These data indicate an important role
      for ETA receptors in ET-1-induced constriction of human pial arteries and suggest
      that ETA receptor antagonists may provide additional dilatory benefit in
      cerebrovascular disorders associated with raised ET levels.

PMID- 10066865
TI  - Prevention of neointimal formation by a serine protease inhibitor, FUT-175, after
      carotid balloon injury in rats.
AB  - BACKGROUND AND PURPOSE: In vivo and vitro studies revealed the activation of
      thrombin and the complement system in vascular lesion formation during the
      process of atherosclerosis, along with pathological proliferation of smooth
      muscle cells. We examined the effect of the synthetic serine protease inhibitor
      FUT-175 (developed as a potent inhibitor of thrombin and the complement system)
      on vascular lesions using balloon dilatation-induced neointimal formation in the
      carotid artery of rats. METHODS: Sprague-Dawley (SD) rats underwent balloon
      dilatation injury of the left carotid artery to induce neointimal formation.
      Three groups of these rats (n=8, each) were treated with daily intraperitoneal
      injections of 1 of the following doses of FUT-175: 0.5, 1.0, or 2.0 mg/d in 1 mL
      of saline for 7 consecutive days. The control group (n=8) was similarly treated
      with 1 mL of saline for 7 days. The injections were started immediately after
      balloon injury. Two weeks after the injury, the left carotid arteries were
      perfusion-fixed, and the areas of the neointimal and medial layer were analyzed
      under a microscope. RESULTS: A morphometric analysis revealed that there were
      significant differences in the intima-media ratio between the 4 groups treated
      with vehicle (saline) or a low, medium, or high dose of FUT-175 (1.45+/-0.11,
      1.08+/-0.06, 0.71+/-0.04, or 0.32+/-0.04, respectively). This suppression was
      achieved in a dose-dependent manner by the administration of FUT-175 after
      balloon injury. In the histological study, it was demonstrated that FUT-175
      suppresses the production of platelet-derived growth factor (PDGF)-BB in the
      neointima and the medial smooth muscle cell layer. CONCLUSIONS: After balloon
      injury activated proteases that were inhibited by FUT-175 were demonstrated to
      have an essential role in the development of the pathological thickening of the
      arterial wall.

PMID- 10066866
TI  - Nicotine increases plasminogen activator inhibitor-1 production by human brain
      endothelial cells via protein kinase C-associated pathway.
AB  - BACKGROUND AND PURPOSE: Smoking both increases stroke risk and reduces the risk
      of thrombolysis-associated intracerebral hemorrhage. Plasminogen activator
      inhibitor-1 (PAI-1) is a major regulator of fibrinolysis; elevation of PAI-1 is
      associated with an increased risk of thrombotic disorders. We studied the effect
      of nicotine, an important constituent of cigarette smoke, on PAI-1 production by
      human brain endothelial cells. METHODS: Adult human central nervous system
      endothelial cells (CNS-EC) were used for tissue culture experiments. We analyzed
      culture supernatant for PAI-1 protein and measured PAI-1 mRNA (by Northern blot
      analysis) and protein kinase C (PK-C) activity. RESULTS: Nicotine at 100 nmol/L
      increased PAI-1 protein production and mRNA expression by CNS-EC. After 72 hours
      of exposure to nicotine, the concentration of secreted PAI-1 in the cell
      supernatant was increased 1.90+/-0.2 fold compared with untreated cells. PAI-1
      mRNA also increased approximately twofold. Inhibition of PK-C completely
      abolished this effect. Nicotine had no effect on the concentration of tissue
      plasminogen activator. CONCLUSIONS: Nicotine increases brain endothelial cell PAI
      1 mRNA expression and protein production via PK-C-dependent pathway. These
      findings provide new insights into why smoking may be associated with
      predisposition to thrombosis and inversely associated with intracerebral
      hemorrhage after therapeutic tissue plasminogen activator therapy.

PMID- 10066867
TI  - Cerebrovascular alterations in protein kinase C-mediated constriction in stroke
      prone rats.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular pressure-dependent constriction may
      involve the smooth muscle production of diacylglycerol, which could facilitate
      constriction by activating protein kinase C (PKC). A dysfunctional PKC system
      could promote the loss of pressure-dependent constriction. We attempted to
      determine whether the alterations in pressure-dependent constriction in the
      middle cerebral arteries (MCAs) observed in relation to stroke development in
      Wistar-Kyoto stroke-prone spontaneously hypertensive rats (SHRsp) were associated
      with defects in the ability of the arteries to constrict in response to PKC
      activation. METHODS: MCAs were sampled from SHRsp before and after stroke
      development and in stroke-resistant Wistar-Kyoto spontaneously hypertensive rats.
      A pressure myograph was used to test the ability of the arteries to constrict in
      response to a 100 mm Hg pressure step and subsequently to contract in response to
      phorbol 12,13-dibutyrate in the presence of nifedipine (3 micromol/L). RESULTS:
      Pressure-dependent constriction and constriction in response to phorbol
      dibutyrate in the MCAs were inhibited by PKC inhibitors (staurosporine [40
      nmol/L], chelerythrine [12 micromol/L], bisindolylmaleimide [5 micromol/L]),
      declined with age before stroke development in SHRsp, and were absent after
      stroke. There was a significant relationship between pressure- and phorbol
      dibutyrate-induced constriction (r=0.815, P<0. 05). CONCLUSIONS: Phorbol esters
      interact with the same activation site as diacylglycerol to stimulate PKC. An
      inability to constrict in response to phorbol dibutyrate may reflect
      unresponsiveness to diacylglycerol and may contribute to the loss of pressure
      dependent constriction associated with stroke in the MCAs of SHRsp. The loss of
      this autoregulatory function before stroke could increase the risk of cerebral
      hemorrhage.

PMID- 10066868
TI  - Continuing postischemic neuronal death in CA1: influence of ischemia duration and
      cytoprotective doses of NBQX and SNX-111 in rats.
AB  - BACKGROUND AND PURPOSE: Transient forebrain ischemia results in a 24- to 72-hour
      delayed loss of CA1 neurons. Previous work has not assessed whether insult
      durations can vary the degree and maturation rate of CA1 injury and whether there
      are different ultrastructural features of death after brief or severe ischemia.
      We also tested whether known cytoprotective drugs achieve permanent or transient
      neuroprotection. METHODS: In the first experiment, ischemia was induced for 5,
      15, or 30 minutes with the use of the 4-vessel occlusion rat model with 1- to 28
      day survival. Others subjected to 5 or 15 minutes of ischemia and allowed to
      survive for 14 or 7 days, respectively, were examined with electron microscopy.
      Finally, we determined whether NBQX (30 mg/kg x3 at 0 or 6 hours after ischemia),
      an AMPA antagonist, and SNX-111 (5 mg/kg at 6 hours after ischemia), an N-type
      Ca2+ channel antagonist, provided enduring CA1 protection against 10 minutes of
      ischemia. RESULTS: CA1 damage was not detected at 24 hours. Thirty minutes of
      ischemia produced 47% and 84% CA1 damage at 2 and 3 days, respectively. A 15
      minute occlusion yielded 11%, 74%, and 86% loss at 2, 3, and 7 days,
      respectively. Five minutes of ischemia produced an even slower progression with
      24%, 52%, and 59% loss at 3, 7, and 14 days, respectively. Ultrastructural
      examination after 5 and 15 minutes of ischemia revealed necrosis with no
      morphological evidence of apoptosis. Both NBQX (P<0.021) and SNX-111 (P<0.001)
      significantly reduced CA1 death at 7 days (</=35%) but not at 28 days (>/=80%)
      compared with saline treatment ( approximately 79%). CONCLUSIONS: Brief forebrain
      ischemia results in a slower progression of CA1 loss than more severe insults.
      Nonetheless, neuronal injury had necrotic, not apoptotic, morphology. NBQX and
      SNX-111 only postponed CA1 injury.

PMID- 10066869
TI  - Nitric oxide production in the CA1 field of the gerbil hippocampus after
      transient forebrain ischemia : effects of 7-nitroindazole and NG-nitro-L-arginine
      methyl ester.
AB  - BACKGROUND AND PURPOSE: The present study was designed to examine the time course
      of nitric oxide (NO) production and the source of NO in the CA1 field of the
      gerbil hippocampus after transient forebrain ischemia. METHODS: The production of
      NO in the CA1 field of the hippocampus after transient ischemia was monitored
      consecutively by measuring total NO metabolites (NOx-, NO2- plus NO3-) with the
      use of brain microdialysis. 7-Nitroindazole (7-NI) and NG-nitro-L-arginine methyl
      ester were used to dissect the relative contributions of neuronal NO synthase and
      endothelial NO synthase to the NO production. The histological outcomes of 7-NI
      in 5- and 10-minute global ischemia were also evaluated. RESULTS: The production
      of NO in the CA1 field of the hippocampus after ischemia was dependent on the
      severity of ischemia. Ischemia for 2 or 5 minutes did not induce a significant
      increase in NOx- levels in the CA1 field of the hippocampus after reperfusion,
      whereas the 10- and 15-minute ischemias produced significant and persistent
      increases in NOx- levels. 7-NI did not inhibit the basal NOx- levels and showed
      no effects on NOx- levels after 5 minutes of ischemia. However, it completely
      inhibited the increased NOx- levels after 10 or 15 minutes of ischemia. 7-NI
      provided minor neuroprotection in 5 minutes but not in 10 minutes of global
      ischemia. CONCLUSIONS: The increased NO level in the CA1 field of the hippocampus
      after ischemia is produced mostly by neuronal NO synthase, whereas the basal NO
      level mainly originates from endothelial NO synthase. The observed
      neuroprotective effect of 7-NI in 5-minute global ischemia in gerbils may not be
      due to neuronal NO synthase inhibition by this drug.

PMID- 10066870
TI  - Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion
      weighted MRI.
AB  - BACKGROUND: Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new
      techniques that can be used for the evaluation of acute ischemic stroke. However,
      their potential role in the management of patients treated with recombinant
      tissue plasminogen activator (rtPA) has yet to be determined. CASE DESCRIPTION:
      The authors present the case of a 73-year-old man who was treated with intra
      arterial rtPA, and they compare findings on DWI and PWI scans with angiography.
      PWI revealed decreased cerebral perfusion corresponding to an area that was not
      successfully recanalized, but revealed no abnormality in regions in which blood
      flow was restored. DWI was unremarkable in the region that was reperfused early
      (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours
      after symptom onset and in the area that was not reperfused. CONCLUSIONS:
      Findings on PWI correlated well with angiography, and DWI detected injured tissue
      in the hyperacute stage, whereas conventional MRI findings were negative. This
      suggests that these techniques may be useful to noninvasively evaluate the
      success of thrombolytic therapy.

PMID- 10066871
TI  - Facial diplegia complicating a bilateral internal carotid artery dissection.
AB  - BACKGROUND AND PURPOSE: We report a case of facial diplegia complicating a
      bilateral internal carotid artery dissection. CASE DESCRIPTION: A 49-year-old
      patient presented with unilateral headache and oculosympathetic paresis. Cerebral
      angiography revealed a bilateral internal carotid artery dissection. A few days
      later, the patient developed a facial diplegia that regressed after arterial
      recanalization. An arterial anatomic variation may explain this ischemic
      complication of carotid dissection. CONCLUSIONS: Double carotid dissection should
      be included among the causes of bilateral seventh nerve palsy.

PMID- 10066872
TI  - Spatz-Lindenberg disease: a rare cause of vascular dementia.
AB  - BACKGROUND: Isolated cerebral thromboangiitis obliterans (Spatz-Lindenberg
      disease) is not well recognized as a cause of vascular dementia. CASE
      DESCRIPTION: A 58-year-old woman presented with dementia and pyramidal signs.
      Neuroimaging showed multiple areas of white matter change. Brain biopsy showed
      intimal thickening of the walls of leptomeningeal and intraparenchymal arteries,
      almost to complete occlusion, with an intact internal elastic lamina and media
      and without inflammation or infiltration. The cortex showed only moderate
      gliosis. CONCLUSIONS: Spatz-Lindenberg disease should be considered in the
      differential diagnosis of vascular dementia. Additional studies of its
      pathogenesis are required to determine appropriate treatment.

PMID- 10066873
TI  - Letters to the editor 

PMID- 10066874
TI  - Therapy of early poststroke depression with venlafaxine: safety, tolerability,
      and efficacy as determined in an open, uncontrolled clinical trial.

PMID- 10066875
TI  - Poststroke pruritus.

PMID- 10066876
TI  - Mitral annulus calcification and carotid atherosclerotic disease.

PMID- 10066877
TI  - Spontaneous stroke in renovascular hypertensive rats.

PMID- 10066879
TI  - Abstracts of literature 

PMID- 10066878
TI  - Amphetamine-facilitated poststroke recovery.

PMID- 10066880
TI  - Therapeutic strategies for coronary artery disease beyond low density lipoprotein
      (LDL)--lowering.
AB  - Coronary artery disease (CAD) ranks as the leading cause of death in the Western
      world. The most widely used therapeutics utilized for the treatment of CAD are
      the lipid-lowering drugs, which lower plasma cholesterol. However lowering
      cholesterol alone may not be sufficient to provide benefit to all patient
      populations at risk for CAD. This creates an unmet medical need. Emerging
      knowledge of the genesis, progression and regression of atherosclerosis, that
      leads to CAD permits evaluation of other therapeutic strategies. This review will
      evaluate two such naturally occurring paradigms, the nitric oxide pathway and the
      high-density lipoprotein system which are nature's defense mechanisms against
      atherosclerosis and may lead to next generation therapeutics against CAD.

PMID- 10066881
TI  - 15-Lipoxygenase and its inhibition: a novel therapeutic target for vascular
      disease.
AB  - The disease process known as atherosclerosis is the leading cause of morbidity
      and mortality in the Western world. Current therapies have focused on treating
      the major risk factors identified to date including plasma lipid derangements,
      hypertension, clotting disorders, and diabetes. However, a significant number of
      individuals will be diagnosed with this malady in the apparent absence of known
      risk factors. Recent attention has turned toward treating the disease at the
      level of the vessel wall. In this review, we assess the relevancy of the
      oxygenating enzyme 15-lipoxygenase (15-LO) as a therapeutic target. In vitro
      studies suggest that this enzyme may be involved in processes that modify native
      LDL in such a way as to be avidly taken up by tissue macrophages. In support of
      this contention are reports demonstrating the colocalization of 15-LO with
      macrophage-rich arterial lesions and epitopes of modified LDL. Investigations
      using transgenic animals also suggest that the site of 15-LO expression may be an
      important factor in the development of the disease. The alteration of important
      cellular fatty acids may also generate intracellular signals that promote a pro
      atherogenic phenotype in the absence of measurable changes in bulk lipid
      peroxidation. A limited number of studies have examined 15-LO inhibitors and
      those structural determinants necessary for inhibition of the enzyme. These
      include natural products and synthetic analogs. Structure activity relationships
      have been defined for a number of compounds including caffeic acid derivatives,
      propargyl ethers, and catechols. A novel, potent, specific inhibitor of 15-LO
      that lacks significant antioxidant activity was tested for its ability to inhibit
      atherosclerotic lesion formation in vivo. This benzothiopyranoindole virtually
      eliminated lesion formation in two animal models in the absence of significant
      changes in plasma lipids. Further, it prevented the progression of pre
      established lesions in another study. Collectively, these data provide a strong
      scientific rationale for exploring the inhibition of 15-LO as a therapeutic
      strategy.

PMID- 10066882
TI  - Parathyroid hormone and parathyroid hormone-related protein: model systems for
      the development of an osteoporosis therapy.
AB  - The parathyroid hormone (PTH) plays a vital role in the homeostasis of calcium
      within the blood stream. Given its unique ability to increase bone density, an
      understanding of the molecular mechanism by which the hormone is recognized and
      binds to its receptor should provide targets for the development of PTH-based,
      anabolic agents for the treatment of osteoporosis. Parathyroid hormone related
      protein (PTHrP), a genetically and structurally distinct hormone which displays
      similar binding and activation profiles as PTH, has greatly facilitated the
      effort to establish a structure-biological function relationship by allowing for
      direct comparisons. In an analogous manner, the presence of two receptors,
      PTH/PTHrP (PTH1) and PTH2, which differ in their ligand selectivity (PTH2 is
      activated by PTH, not PTHrP) has provided a unique vehicle for probing the
      structural motifs of the receptor required for ligand recognition and binding.
      Recent photo-affinity cross-linking studies of PTH and PTHrP binding to PTH1 have
      produced direct points of contact between the ligand and receptor. Here, we
      review each of the components involved in this important hormone system, with
      particular emphasis on the structural features of each: the ligands (PTH and
      PTHrP), the receptors (PTH1 and PTH2), and the interaction between ligand and
      receptor. Although the current understanding of the molecular mechanism of ligand
      binding and receptor activation does not allow for the rational design of drug
      candidates, and indeed contains much conjecture, significant strides have been
      made towards this end.

PMID- 10066883
TI  - Methicillin-resistance in Staphylococcus aureus - molecular basis, novel targets
      and antibiotic therapy.
AB  - Methicillin-resistant S. aureus are the major cause of nosocomial bacteremias
      showing a high morbidity rate in intensive care units. These strains are often
      resistant against almost all antibiotics in clinical use with the exception of
      vancomycin. However, the first isolation of a S. aureus strain with a diminished
      susceptibility to vancomycin from a hospitalized patient in Japan has been
      reported very recently. Therefore, current antibiotic therapy is difficult and
      expensive, often a combination of several antibiotics has to be used. For this
      reason novel antibiotics to combat staphylococcal bacteremias, which prevent
      further spread of resistance are urgently needed. One approach might be the
      investigation of the mechanism of methicillin resistance, which is mediated by
      PBP2a, an additional penicillin-binding protein present in resistant strains with
      low affinity to ss-lactams. Beside PBP2a other housekeeping genes, the so called
      fem factors, are involved in expression of methicillin resistance. Two of these
      fem factors, the FemAB proteins, have been shown to participate in the formation
      of the pentaglycine crossbridge, which is a unique staphylococcal cell wall
      component. The biosynthesis of the pentaglycine side chains is not fully
      elucidated, but follows an interesting novel mechanism with unusual glycyl-tRNA
      as a substrate. Furthermore, inactivation of femAB, which have been reported as
      essential for bacterial growth, causes a completely restoration of antibiotic
      susceptibility in MRSA strains. Thus, these proteins might serve as attractive
      novel anti-staphylococcal targets for a small-range antibiotic.

PMID- 10066884
TI  - Design and preparation of cyclopeptamine antifungal agents.
AB  - The lack of agents for infections caused by pathogenic fungi has demanded further
      investigation of a key lead structure which has shown promise, echinocandin B. In
      recent years, two analogs of this cyclic hexapeptide are proceeding through the
      clinic exhibiting proof of concept for the target of these drugs. This target,
      the ss-1,3-glucan synthesis complex, produces the majority of fungal cell wall
      glucan in many of the most pathogenic fungi such as Candida. A methodical
      structure-activity relationship review of several major fragments of these highly
      functionalized molecules is described. This information is useful for
      determination of the minimum functional/structural requirements for design of an
      optimal compound in this series. Analogs are presented with their accompanying
      whole cell antifungal activities.

PMID- 10066885
TI  - Polyoxins and nikkomycins: progress in synthetic and biological studies.
AB  - Polyoxins and nikkomycins are naturally-occurring peptidyl nucleoside
      antibiotics. As inhibitors of chitin synthetase, they exhibit antifungal
      activity, but lack antibacterial activity. Since they also lack mammalian
      toxicity, they represent potentially useful models for the development of
      effective agents for the treatment of opportunistic fungal infections. Direct
      clinical application of the natural peptidyl nucleosides is compromised by their
      attenuated in vivo activity, apparently due to their hydrolytic lability and
      inefficient fungal cell wall permeability. Thus, extensive efforts have focused
      on syntheses of natural peptidyl nucleosides, their components and analogs in
      anticipation of establishing useful structure-activity-relationships (SAR) for
      the development of new antifungal agents. A comprehensive and critical review of
      the synthetic effort and subsequent biological studies reveals that while much
      has been accomplished, ideal antifungal agents have not yet been developed from
      the natural peptidyl nucleoside leads. The need for continued study of agents
      with novel modes of action is emphasized by the realization that other
      structurally varied antifungal agents currently used clinically have limitations
      and often severe side effects, including nephrotoxicity.

PMID- 10066886
TI  - Current progress in the chemistry, medicinal chemistry and drug design of
      artemisinin based antimalarials.
AB  - This review covers developments in relation to artemisinin-based antimalarial
      agents. Topics covered include a brief introduction to the history and treatment
      of malaria, and more recently, drug resistant malaria; the discovery of the
      naturally occurring novel peroxidic antimalarial artemisinin; artemisinin
      biosynthesis, metabolism and biotransformations; the diversity of proposed
      mechanisms of action; pharmacokinetics; the insight into structure-toxicity
      relationships; the total syntheses and the progress made in the syntheses of its
      analogs; and, ultimately the contribution of these efforts towards rational drug
      design in order to access potent, non-toxic antimalarial drugs based on
      artemisinin.

PMID- 10066887
TI  - The dolastatins, a family of promising antineoplastic agents.
AB  - The dolastatins and some related compounds are antineoplastic pseudopeptides
      isolated from the sea hare Dolabella auricularia by the groups of G. R. Pettit
      and K. Yamada. Several groups including ours have contributed to the development
      of synthetic routes to most of these compounds. We recently described the
      synthesis of dolatrienoic acid, the lipidic component of dolastatin 14. Among all
      these metabolites, dolastatin 10 and dolastatin 15 exhibit the most promising
      antiproliferative properties and are currently under evaluation in clinical
      trials. These antimitotic agents seem to exert their activity by interacting with
      tubulin and inducing apoptosis. Research in this domain could greatly benefit
      from the recent elucidation of the atomic structure of tubulin. However, other
      targets cannot be excluded. Elucidation of the structure-activity relationships
      is an important step in the development of therapeutic agents. Parallel to the
      studies developed by other groups, our approach to exploring structural
      requirements for the antineoplastic activity of these compounds involved the
      determination of their preferred conformations in solution. Our study showed that
      dolastatin 10 exists in two different conformations corresponding to a cis-trans
      isomerization of a central amide bond. Such a situation was not demonstrated in
      the case of dolastatin 15. In view of elucidating the biological relevance of
      these findings, we elaborated hybrid molecules constituted of parts of both
      compounds. We also synthesized a cyclic analogue of dolastatin 10 which locked
      this compound in its cis conformation. Our results as well as those of others
      could be interpreted in terms of an existing structural model.

PMID- 10066888
TI  - Inhibitors of 17alpha-hydroxylase/17,20-lyase (CYP17): potential agents for the
      treatment of prostate cancer.
AB  - Prostate cancer (PCa) is now the most prevalent cancer in men in the U.S.A. and
      Europe. At present the major treatment options include surgical or medical
      castration. These strategies depend on the abolition of the production of
      testosterone by the testes. However, as these procedures do not affect adrenal
      androgen production, they are frequently combined with androgen receptor
      antagonist to block their action. Inhibition of the key enzyme which catalyzes
      the biosynthesis of androgens from pregnane precursors, 17alpha-hydroxylase/17,20
      lyase (hereafter referred to as CYP17 ) could prevent androgen biosynthesis from
      both sources. Thus total blockade of androgen production by CYP17 inhibitors may
      provide effective treatment of prostate cancer patients. Indeed, this strategy is
      now an area of intense interest within research institutions and the
      pharmaceutical industry. This review highlights development in the design and
      evaluation of both steroidal and non-steroidal CYP17 inhibitors since 1965. Major
      emphasis is given to the potent CYP17 inhibitors and those which may show
      clinical promise. The review could function as a comprehensive working reference
      of research accomplishment in the field and what problems remain to be tackled in
      the future.

PMID- 10066889
TI  - Fused azepinones with antitumor activity.
AB  - Based on the observation that some simple [1]benzazepin-2-ones exhibit in vivo
      antitumor activity, studies directed to several new structure classes with this
      partial motif have been reported recently, comprising 7,12-dihydro-indolo[3, 2
      d][1]benzazepin-6(5H)-ones (paullones), 5H-qui nolino[3, 2-d][1]benzazepin-6(7H)
      ones, 2,4-diaryl-5H-pyrido[3, 2-d][1]benzazepin-6(7H)-ones, spiro[1-benzazepine
      4,1 -cyclohexane] deriva-tives, and naphthannelated benzazepinones. For the
      syntheses of these heterocyclic compounds, 1H-[1]benzazepine-2,5(3H,4H)-diones
      were employed as readily available starting materials. In each of the mentioned
      series, entities with in vitro antitumor activity have been detected. Considering
      potency and in vitro cell line selectivity, both the 2,4-diaryl-5H-pyrido[3, 2
      d][1]benzazepin-6(7H)-ones and the paullones are apparently suitable for a
      further development. A biological mechanism probably related to the anti
      proliferative activity has been established only for the paullones. These
      compounds represent a novel class of selective inhibitors of cyclin-dependent
      kinases, a family of enzymes whose function seems to be deregulated in many human
      tumors.

PMID- 10066890
TI  - Drugs acting on DNA topoisomerases: recent advances and future perspectives.
AB  - DNA-topoisomerases, a family of DNA-processing enzymes, represent the
      pharmacological target of major clinically useful chemotherapeutic agents. These
      drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an
      intermediate in the enzyme s catalytic cycle. Research activity in this field
      continues to grow exponentially, resulting in a wealth of new information on the
      functional role and the biochemical and structural properties of the enzymes. In
      addition, the drug pharmacophores have been further characterized, along with
      their sequence preferences, and key interactions with the target macromolecules
      are being unveiled. This review will discuss the recent advances in elucidating
      the mode of action of DNA-topoisomerases and of topoisomerase-targeted anticancer
      agents.

PMID- 10066891
TI  - Ring-B modified anthracyclines.
AB  - One of the most investigated classes of antitumor drugs is represented by
      anthracyclines. Over thirty years since the original discovery of daunorubicin
      and doxorubicin thousands of anthracycline analogues have been synthesized and
      tested to identify compounds superior to the parent drugs in terms of increased
      therapeutic effectiveness, reduced toxicity or both. Previous structure-activity
      studies had shown that minor modifications of the anthracycline structure can
      result not only in active agents, but, more importantly, analogues with reduced
      cardiotoxicity and activity on multi drug resistance. The fact that 4
      demethoxydaunorubicin showed higher potency than daunorubicin and a reduced
      cardiotoxicity, prompted us to explore novel analogues with altered substitution
      patterns on the anthraquinone system, particularly ring-B. In this review we will
      describe total synthesis and antitumor activity of three classes of derivatives:
      whereby one hydroxyl group in ring-B was either removed or replaced with nitro or
      amino groups. While these modifications yielded anthracyclines with a promising
      pharmacological activity, they did not modify activity on multidrug resistant
      (MDR) tumors. On the other hand, introduction of morpholino group in the sugar
      part of these new molecules, dramatically increased activity on MDR tumors. We
      conclude that activity on MDR tumors is not bound to modifications in the
      aglycone moiety of anthracyclines.

PMID- 10066892
TI  - Surprising diversity in axonal properties between the different functional
      classes of neurone in peripheral nerves.

PMID- 10066893
TI  - Selective activation of heterologously expressed G protein-gated K+ channels by
      M2 muscarinic receptors in rat sympathetic neurones.
AB  - 1. G protein-regulated inward rectifier K+ (GIRK) channels were over-expressed in
      dissociated rat superior cervical sympathetic (SCG) neurones by co-transfecting
      green fluorescent protein (GFP)-, GIRK1- and GIRK2-expressing plasmids using the
      biolistic technique. Membrane currents were subsequently recorded with whole-cell
      patch electrodes. 2. Co-transfected cells had larger Ba2+-sensitive inwardly
      rectifying currents and 13 mV more negative resting potentials (in 3 mM [K+]o)
      than non-transfected cells, or cells transfected with GIRK1 or GIRK2 alone. 3.
      Carbachol (CCh, 1-30 microM) increased the inwardly rectifying current in 70 % of
      GIRK1+ GIRK2-transfected cells by 261 +/- 53 % (n = 6, CCh 30 microM) at -120 mV,
      but had no effect in non-transfected cells or in cells transfected with GIRK1 or
      GIRK2 alone. Pertussis toxin prevented the effect of carbachol but had no effect
      on basal currents. 4. The effect of CCh was antagonized by 6 nM tripitramine but
      not by 100 nM pirenzepine, consistent with activation of endogenous M2 muscarinic
      acetylcholine receptors. 5. In contrast, inhibition of the voltage-activated Ca2+
      current by CCh was antagonized by 100 nM pirenzepine but not by 6 nM
      tripitramine, indicating that it was mediated by M4 muscarinic acetylcholine
      receptors. 6. We conclude that endogenous M2 and M4 muscarinic receptors
      selectively couple to GIRK currents and Ca2+ currents respectively, with
      negligible cross-talk.

PMID- 10066894
TI  - Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth
      muscle cells.
AB  - 1. The molecular nature of the strong inward rectifier K+ channel in vascular
      smooth muscle was explored by using isolated cell RT-PCR, cDNA cloning and
      expression techniques. 2. RT-PCR of RNA from single smooth muscle cells of rat
      cerebral (basilar), coronary and mesenteric arteries revealed transcripts for
      Kir2.1. Transcripts for Kir2.2 and Kir2.3 were not found. 3. Quantitative PCR
      analysis revealed significant differences in transcript levels of Kir2.1 between
      the different vascular preparations (n = 3; P < 0.05). A two-fold difference was
      detected between Kir2.1 mRNA and beta-actin mRNA in coronary arteries when
      compared with relative levels measured in mesenteric and basilar preparations. 4.
      Kir2.1 was cloned from rat mesenteric vascular smooth muscle cells and expressed
      in Xenopus oocytes. Currents were strongly inwardly rectifying and selective for
      K+. 5. The effect of extracellular Ba2+, Ca2+, Mg2+ and Cs2+ ions on cloned
      Kir2.1 channels expressed in Xenopus oocytes was examined. Ba2+ and Cs+ block
      were steeply voltage dependent, whereas block by external Ca2+ and Mg2+ exhibited
      little voltage dependence. The apparent half-block constants and voltage
      dependences for Ba2+, Cs+, Ca2+ and Mg2+ were very similar for inward rectifier
      K+ currents from native cells and cloned Kir2.1 channels expressed in oocytes. 6.
      Molecular studies demonstrate that Kir2.1 is the only member of the Kir2 channel
      subfamily present in vascular arterial smooth muscle cells. Expression of cloned
      Kir2.1 in Xenopus oocytes resulted in inward rectifier K+ currents that strongly
      resemble those that are observed in native vascular arterial smooth muscle cells.
      We conclude that Kir2.1 encodes for inward rectifier K+ channels in arterial
      smooth muscle.

PMID- 10066895
TI  - Identification, cloning and expression of rabbit vascular smooth muscle Kv1.5 and
      comparison with native delayed rectifier K+ current.
AB  - 1. The molecular basis of voltage-gated, delayed rectifier K+ (KDR) channels in
      vascular smooth muscle cells is poorly defined. In this study we employed (i) an
      antibody against Kv1.5 and (ii) a cDNA clone encoding Kv1.5 derived from rabbit
      portal vein (RPV) to demonstrate Kv1.5 expression in RPV and to compare the
      properties of RPVKv1.5 expressed in mammalian cells with those of native RPV KDR
      current. 2. Expression of Kv1.5 channel protein in RPV was demonstrated by (i)
      immunocytolocalization of an antibody raised against a C-terminal epitope of
      mouse cardiac Kv1.5 in permeabilized, freshly isolated RPV smooth muscle cells
      and (ii) isolation of a cDNA clone encoding RPVKv1.5 by reverse transcription
      polymerase chain reaction (RT-PCR) using mRNA derived from endothelium-denuded
      and adventitia-free RPV. 3. RPVKv1.5 cDNA was expressed in mammalian L cells and
      human embryonic kidney (HEK293) cells and the properties of the expressed
      channels compared with those of native KDR channels of freshly dispersed myocytes
      under identical conditions. 4. The kinetics and voltage dependence of activation
      of L cell-expressed RPVKv1.5 and native KDR current were identical, as were the
      kinetics of recovery from inactivation and single channel conductance. In
      contrast, there was little similarity between HEK293 cell-expressed RPVKv1.5 and
      native KDR current. 5. Inactivation occurred with the same voltage for half
      maximal availability, but the kinetics and slope constant for the voltage
      dependence of inactivation for L cell-expressed RPVKv1.5 and the native current
      were different: slow time constants were 6.5 +/- 0.6 and 3.5 +/- 0.4 s and slope
      factors were 4.7 +/- 0.2 and 7.0 +/- 0.8 mV, respectively. 6. This study provides
      immunofluorescence and functional evidence that Kv1.5 alpha-subunits are a
      component of native KDR channels of vascular smooth muscle cells of RPV. However,
      the differences in kinetics and voltage sensitivity of inactivation between L
      cell- and HEK293 cell-expressed channels and native KDR channels provide
      functional evidence that vascular KDR current is not due to homomultimers of RPV
      Kv1.5 alone. The channel structure may be more complex, involving heteromultimers
      and modulatory Kvbeta-subunits, and/or native KDR current may have other
      components involving Kvalpha-subunits of other families.

PMID- 10066896
TI  - Regulation of an amiloride-sensitive Na+-permeable channel by a beta2-adrenergic
      agonist, cytosolic Ca2+ and Cl- in fetal rat alveolar epithelium.
AB  - 1. In cell-attached patches formed on the apical membrane of fetal alveolar
      epithelium, terbutaline (a specific beta2-adrenergic agonist) increased the open
      probability (Po) of an amiloride-sensitive Na+-permeable non-selective cation
      (NSC) channel (control, 0.03 +/- 0.04; terbutaline, 0.62 +/- 0.18; n = 8, P < 0.
      00001) by increasing the mean open time 100-fold without any significant change
      in the mean closed time and without any change in the single channel conductance
      (control, 27.8 +/- 2.3 pS; terbutaline, 28.2 +/- 2.1 pS; n = 8). 2. The Po of the
      unstimulated channel increased when the apical membrane was depolarized due to a
      decrease in the closing rate and an increase in the opening rate, while the Po of
      the terbutaline-stimulated channel did not depend on the membrane potential. 3.
      Increased cytosolic [Ca2+] also increased the Po of the channel in a manner
      consistent with one Ca2+-binding site on the cytosolic surface of the channel.
      Terbutaline increased the sensitivity of the channel to cytosolic Ca2+ by
      shifting the concentration of cytosolic Ca2+ ([Ca2+]c) required for half-maximal
      activation to a lower [Ca2+]c value, leading to an increase in Po. 4. An increase
      in the cytosolic Cl- concentration ([Cl-]c) decreased the Po of the channel
      consistent with two Cl--binding sites by increasing the closing rate without any
      significant change in the opening rate. Terbutaline increased Po by reducing the
      effect of cytosolic Cl- to promote channel closing. 5. Taken together, these
      observations indicate that terbutaline activates a Ca2+-activated, Cl-
      inhibitable, amiloride-sensitive, Na+-permeable NSC channel in fetal rat alveolar
      epithelium in two ways: first, through an increase in Ca2+ sensitivity, and
      second, through a reduction in the effect of cytosolic Cl- to promote channel
      closing.

PMID- 10066897
TI  - Differential plasma membrane targeting of voltage-dependent calcium channel
      subunits expressed in a polarized epithelial cell line.
AB  - 1. Voltage-dependent calcium channels (VDCCs) show a highly non-uniform
      distribution in many cell types, including neurons and other polarized secretory
      cells. We have examined whether this can be mimicked in a polarized epithelial
      cell line (Madin-Darby canine kidney), which has been used extensively to study
      the targeting of proteins. 2. We expressed the VDCC alpha1A, alpha1B or alpha1C
      subunits either alone or in combination with accessory subunits alpha2-delta and
      the different beta subunits, and examined their localization
      immunocytochemically. An alpha1 subunit was only targeted to the plasma membrane
      if co-expressed with the accessory subunits. 3. The combination alpha1C/alpha2
      delta and all beta subunits was always localized predominantly to the basolateral
      membrane. It has been suggested that this is equivalent to somatodendritic
      targeting in neurons. 4. In contrast, the alpha1B subunit was expressed at the
      apical membrane with all the accessory subunit combinations, by 24 h after
      microinjection. This membrane destination shows some parallels with axonal
      targeting in neurons. 5. The alpha1A subunit was consistently observed at the
      apical membrane in the combinations alpha1A/alpha2-delta/beta1b or beta4. In
      contrast, when co-expressed with alpha2-delta/beta2a, alpha1A was clearly
      targeted to the basolateral membrane. 6. In conclusion, the VDCC alpha1 subunit
      appears to be the primary determinant for targeting the VDCC complex, but the
      beta subunit can modify this destination, particularly for alpha1A.

PMID- 10066898
TI  - Cross-coupling between voltage-dependent Ca2+ channels and ryanodine receptors in
      developing ascidian muscle blastomeres.
AB  - 1. Ascidian blastomeres of muscle lineage express voltage-dependent calcium
      channels (VDCCs) despite isolation and cleavage arrest. Taking advantage of these
      large developing cells, developmental changes in functional relations between
      VDCC currents and intracellular Ca2+ stores were studied. 2. Inactivation of
      ascidian VDCCs is Ca2+ dependent, as demonstrated by two pieces of evidence: (1)
      a bell-shaped relationship between prepulse voltage and amplitude during the test
      pulse in Ca2+, but not in Ba2+, and (2) the decay kinetics of Ca2+ currents (ICa)
      obtained as the size of tail currents. 3. During replacement in the external
      solution of Ca2+ with Ba2+, the inward current appeared biphasic: it showed rapid
      decay followed by recovery and slow decay. This current profile was most evident
      in the mixed bath solution (2 % Ca2+ and 98 % Ba2+, abbreviated to '2Ca/98Ba').
      4. The biphasic profile of I2Ca/98Ba was significantly attenuated in caffeine and
      in ryanodine, indicating that Ca2+ release is involved in shaping the current
      kinetics of VDCCs. After washing out the caffeine, the biphasic pattern was
      reproducibly restored by depolarizing the membrane in calcium-rich solution,
      which is expected to refill the internal Ca2+ stores. 5. The inhibitors of
      endoplasmic reticulum (ER) Ca2+-ATPase (SERCAs) cyclopiazonic acid (CPA) and
      thapsigargin facilitated elimination of the biphasic profile with repetitive
      depolarization. 6. At a stage earlier than 36 h after fertilization, the biphasic
      profile of I2Ca/98Ba was not observed. However, caffeine induced a remarkable
      decrease in the amplitude of I2Ca/98Ba and this suppression was blocked by
      microinjection of the Ca2+ chelator BAPTA, showing the presence of caffeine
      sensitive Ca2+ stores at this stage. 7. Electron microscopic observation shows
      that sarcoplasmic membranes (SR) arrange closer to the sarcolemma with
      maturation, suggesting that the formation of the ultrastructural machinery
      underlies development of the cross-coupling between VDCCs and Ca2+ stores.

PMID- 10066899
TI  - Receptor system response kinetics reveal functional subtypes of native murine and
      recombinant human GABAA receptors.
AB  - 1. Regional distinctions in GABA type A (GABAA) miniature IPSC responses are
      thought to be determined by postsynaptic receptor composition. The kinetics of
      receptor activation and deactivation were studied using rapid exchange (100
      micros) of GABA at excised patches containing recombinant (alpha1beta1gamma2 or
      alpha2beta1gamma2) and native (cortical) GABAA receptors. 2. Receptors activated
      by brief (< 1 ms) pulses of GABA demonstrated a characteristic current response,
      hereby referred to as the 'receptor system response'. System response properties
      included agonist concentration-dependent peak amplitudes and concentration
      independent maximal rates of activation and deactivation. Receptor subtypes were
      characterized functionally and phenotyped using the system response
      characteristics. 3. System responses obtained for alpha1beta1gamma2 receptors
      exhibited a single phenotype while alpha2beta1gamma2 receptors exhibited either a
      predominant slow deactivation (type I) or a relatively infrequent faster (type
      II) phenotype. Receptor system responses of alpha2beta1gamma2 receptors reached
      peak currents twice as fast as those of alpha1beta1gamma2 receptors (0.5 versus
      1.0 ms) but decayed 2 or 6 times more slowly (taulong of approximately 190 and 62
      ms for type I and II alpha2beta1gamma2, and approximately 34 ms for
      alpha1beta1gamma2 receptors). 4. Receptor system responses from cultured fetal
      mouse cortical neurons could be statistically separated and classified into five
      major types with little intragroup variability, primarily based on variations in
      the current deactivation phases. 5. Receptors subjected to pharmacological
      modulation exhibited alterations in system response properties consistent with
      known mechanisms of action, such that distinctions between binding and gating
      modulations were possible. 6. Brief agonist exposure places limits on receptor
      activation and deactivation response kinetics. Consequently, receptor system
      responses may be used to characterize and functionally phenotype an excised patch
      receptor population. Furthermore, since synaptic exposure to transmitter is
      postulated to be similarly brief, IPSC kinetics may reflect a functional
      fingerprint of synaptic receptors.

PMID- 10066900
TI  - Ion binding and permeation through the lepidopteran amino acid transporter KAAT1
      expressed in Xenopus oocytes.
AB  - 1. The transient and steady-state currents induced by voltage jumps in Xenopus
      oocytes expressing the lepidopteran amino acid co-transporter KAAT1 have been
      investigated by two-electrode voltage clamp. 2. KAAT1-expressing oocytes
      exhibited membrane currents larger than controls even in the absence of amino
      acid substrate (uncoupled current). The selectivity order of this uncoupled
      current was Li+ > Na+ approximately Rb+ approximately K+ > Cs+; in contrast, the
      permeability order in non-injected oocytes was Rb+ > K+ > Cs+ > Na+ > Li+. 3.
      KAAT1-expressing oocytes gave rise to 'pre-steady-state currents' in the absence
      of amino acid. The characteristics of the charge movement differed according to
      the bathing ion: the curves in K+ were strongly shifted (> 100 mV) towards more
      negative potentials compared with those in Na+, while in tetramethylammonium
      (TMA+) no charge movement was detected. 4. The charge-voltage (Q-V) relationship
      in Na+ could be fitted by a Boltzmann equation having V of -69 +/- 1 mV and slope
      factor of 26 +/- 1 mV; lowering the Na+ concentrations shifted the Q-V
      relationship to more negative potentials; the curves could be described by a
      generalized Hill equation with a coefficient of 1.6, suggesting two binding
      sites. The maximal movable charge (Qmax) in Na+, 3 days after injection, was in
      the range 2.5-10 nC. 5. Addition of the transported substrate leucine increased
      the steady-state carrier current, the increase being larger in high K+ compared
      with high Na+ solution; in these conditions the charge movement disappeared. 6.
      Applying Eyring rate theory, the energy profile of the transporter in the absence
      of organic substrate included a very high external energy barrier (25.8 RT units)
      followed by a rather deep well (1.8 RT units).

PMID- 10066901
TI  - Passive electrotonic properties of rat hippocampal CA3 interneurones.
AB  - 1. The linear membrane responses of CA3 interneurones were determined with the
      use of whole-cell patch recording methods. The mean input resistance (RN) for all
      cells in this study was 526 +/- 16 MOmega and the slowest membrane time constant
      (tau0) was 73 +/- 3 ms. 2. The three-dimensional morphology of 63 biocytin
      labelled neurones was used to construct compartmental models. Specific membrane
      resistivity (Rm) and specific membrane capacitance (Cm) were estimated by fitting
      the linear membrane response. Acceptable fits were obtained for 24 CA3
      interneurones. The mean Rm was 61.9 +/- 34.2 Omega cm2 and the mean Cm was 0.9 +/
      0.3 microF cm-2. Intracellular resistance (Ri) could not be resolved in this
      study. 3. Examination of voltage attenuation revealed a significantly low
      synaptic efficiency from most dendritic synaptic input locations to the soma. 4.
      Simulations of excitatory postsynaptic potentials (EPSPs) were analysed at both
      the site of synaptic input and at the soma. There was little variability in the
      depolarization at the soma from synaptic inputs placed at different locations
      along the dendritic tree. The EPSP amplitude at the site of synaptic input was
      progressively larger with distance from the soma, consistent with a progressive
      increase in input impedance. 5. The 'iso-efficiency' of spatially different
      synaptic inputs arose from two opposing factors: an increase in EPSP amplitude at
      the synapse with distance from the soma was opposed by a nearly equivalent
      increase in voltage attenuation. These simulations suggest that, in these
      particular neurones, the amplitude of EPSPs measured at the soma will not be
      significantly affected by the location of synaptic inputs.

PMID- 10066902
TI  - Long-term suppression of synaptic transmission by tetanization of a single
      pyramidal cell in the mouse hippocampus in vitro.
AB  - 1. The consequences of stimulating a single pyramidal cell in the CA1 area of the
      hippocampus for synaptic transmission in the stratum radiatum were investigated.
      2. Tetanic activation of single pyramids caused by depolarizing current
      injection, but not an equal number of distributed action potentials, reduced
      excitatory transmission by 20 %, with a delayed onset, for more than 1 h. 3.
      EPSPs in the tetanized pyramidal cells were increased for equally long periods
      but this was not the cause of the field EPSP reduction. Spontaneous somatic IPSPs
      were not affected; evoked IPSPs were decreased in the tetanized cell. 4. Paired
      pulse facilitation of the field EPSPs was unchanged. 5. The field EPSP reduction
      was markedly diminished by a knife cut along the base of pyramidal cells in CA1.
      6. The addition of antagonists of GABA, NMDA and metabotropic glutamate receptors
      blocked or diminished the field EPSP slope reduction evoked by intracellular
      stimulation. 7. Simultaneous recordings revealed long-lasting excitations of
      interneurons located in the outer oriens layer as a result of single pyramid
      tetanization. 8. Intense firing of small numbers of pyramidal cells can thus
      persistently inhibit mass transmission through the hippocampus. This effect
      involves activation of interneurons by glutamate receptors.

PMID- 10066903
TI  - Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal
      organotypic cultures and slices.
AB  - 1. Whole-cell clamp recordings of the compound synaptic current elicited by
      afferent stimulation of Schaffer collaterals showed that blockade of the NMDA,
      AMPA and GABAA receptor-mediated components by 6-nitro-7-sulphamoyl-
      benzo(f)quinoxaline-2,3-dione (NBQX), 3-((R)-2-carboxypiperazine-4-yl)propyl-1
      phosphonate (R-CPP) and picrotoxin, respectively, left a small residual current
      in 39 out of 41 CA1 pyramidal neurones in organotypic cultures and 9 out of 16
      CA1 cells in acutely prepared slices. 2. This current represented 2. 9 +/- 0.4 %
      of the compound evoked synaptic response in organoypic cultures and 1.4 +/- 0.5 %
      in slices. It was characterized by a slightly rectifying I-V curve and a reversal
      potential of 3.4 +/- 5. 1 mV. 3. This residual current was insensitive to
      blockers of GABAB, purinergic, muscarinic and 5-HT3 receptors, but it was
      essentially blocked by the nicotinic receptor antagonist d-tubocurarine (91 +/- 4
      % blockade; 20 microM), and partly blocked by alpha-bungarotoxin (200 nM) and
      methyllycaconitine (10 nM), two antagonists with a higher selectivity for alpha7
      subunit-containing nicotinic receptors (48 +/- 3 % and 55 +/- 11 % blockade,
      respectively). 4. The residual current was of synaptic origin, since it occurred
      after a small delay; its amplitude depended upon the stimulation intensity and it
      was calcium dependent and blocked by the sodium channel antagonist tetrodotoxin.
      5. We conclude that afferent stimulation applied in the stratum radiatum evokes
      in some hippocampal neurones a small synaptic current mediated by activation of
      neuronal nicotinic receptors.

PMID- 10066904
TI  - On the mechanism of histaminergic inhibition of glutamate release in the rat
      dentate gyrus.
AB  - 1. Histaminergic depression of excitatory synaptic transmission in the rat
      dentate gyrus was investigated using extracellular and whole-cell patch-clamp
      recording techniques in vitro. 2. Application of histamine (10 microM, 5 min)
      depressed synaptic transmission in the dentate gyrus for 1 h. This depression was
      blocked by the selective antagonist of histamine H3 receptors, thioperamide (10
      microM). 3. The magnitude of the depression caused by histamine was inversely
      related to the extracellular Ca2+ concentration. Application of the N-type
      calcium channel blocker omega-conotoxin (0. 5 or 1 microM) or the P/Q-type
      calcium channel blocker omega-agatoxin (800 nM) did not prevent depression of
      synaptic transmission by histamine. 4. The potassium channel blocker 4
      aminopyridine (4-AP, 100 microM) enhanced synaptic transmission and reduced the
      depressant effect of histamine (10 microM). 4-AP reduced the effect of histamine
      more in 2 mM extracellular calcium than in 4 mM extracellular calcium. 5.
      Histamine (10 microM) did not affect the amplitude of miniature excitatory
      postsynaptic currents (mEPSCs) and had only a small effect on their frequency. 6.
      Histaminergic depression was not blocked by an inhibitor of serine/threonine
      protein kinases, H7 (100 microM), or by an inhibitor of tyrosine kinases,
      Lavendustin A (10 microM). 7. Application of adenosine (20 microM) or the
      adenosine A1 agonist N6-cyclopentyladenosine (CPA, 0.3 microM) completely
      occluded the effect of histamine (10 microM). 8. We conclude that histamine,
      acting on histamine H3 receptors, inhibits glutamate release by inhibiting
      presynaptic calcium entry, via a direct G-protein-mediated inhibition of multiple
      calcium channels. Histamine H3 receptors and adenosine A1 receptors act upon a
      common final effector to cause presynaptic inhibition.

PMID- 10066905
TI  - Distribution of cholinergic contacts on Renshaw cells in the rat spinal cord: a
      light microscopic study.
AB  - 1. Cholinergic terminals in the rat spinal cord were revealed by
      immunohistochemical detection of the vesicular acetycholine transporter (VAChT).
      In order to determine the relationships of these terminals to Renshaw cells, we
      used dual immunolabelling with antibodies against gephyrin or calbindin D28k to
      provide immunohistochemical identification of Renshaw cells in lamina VII of the
      ventral horn. 2. A total of 50 Renshaw cells were analysed quantitatively using a
      computer-aided reconstruction system to provide accurate localization of contact
      sites and determination of somatic and dendritic surface area. Dendrites could be
      traced for up to 413 microm from the soma in calbindin D28k-identified Renshaw
      cells and up to 184 microm in gephyrin-identified cells. 3. A total of 3330
      cholinergic terminals were observed on 50 Renshaw cells, with a range of 21-138
      terminal appositions per cell (mean 66.6 +/- 25.56 contacts per cell). The vast
      majority (83.5 %) of the terminals were apposed to dendrites rather than the
      soma. The overall density of cholinergic contacts increased from a little above 1
      per 100 microm2 on the soma and initial 25 microm of proximal dendrites to 4-5
      per 100 microm2 on the surface of dendritic segments located 50-250 microm from
      the soma. Single presynaptic fibres frequently formed multiple contacts with the
      soma and/or dendrites of individual Renshaw cells. 4. VAChT-immunoreactive
      terminals apposed to Renshaw cells varied in size from 0.6 to 6.9 microm in
      diameter (mean 2.26 +/- 0.94; n = 986) and were on average smaller than the
      cholinergic C-terminals apposed to motoneurones, but larger than VAChT
      immunoreactive terminals contacting other ventral horn interneurones. 5. The high
      density and relatively large size of many cholinergic terminals on Renshaw cells
      presumably correlates with the strong synaptic connection between motoneurones
      and Renshaw cells. The fact that the majority of contacts are distributed over
      the dendrites makes the motoneurone axon collateral input susceptible to
      inhibition by the prominent glycinergic inhibitory synapses located on the soma
      and proximal dendrites. The relative positions and structural features of the
      excitatory cholinergic and inhibitory glycinergic synapses may explain why
      Renshaw cells, although capable of firing at very high frequency following motor
      axon stimulation, appear to fire at relatively low rates during locomotor
      activity.

PMID- 10066906
TI  - Activity-dependent slowing of conduction differentiates functional subtypes of C
      fibres innervating human skin.
AB  - 1. The effects of impulse activity on conduction in cutaneous C fibres have been
      examined in 46 microneurographic recordings from 11 normal subjects and 11
      diabetic patients with normal nerve conduction. A tungsten microelectrode was
      inserted into a cutaneous nerve, usually the superficial peroneal close to the
      ankle, and intraneural microstimulation was used to identify an area of skin
      innervated. Three minute trains of 0.25 ms stimuli at 1, 2 and 4 Hz were then
      delivered to the surface of the skin, separated by intervals of 6 min with
      stimulation at 0.25 Hz. Slowing and block of conduction were measured from the
      nerve responses for up to seven C units per stimulation sequence. 2. Three types
      of C unit were distinguished by their responses to repetitive stimulation: type 1
      units slowed progressively during the 3 min trains; slowing of type 2 units
      reached a plateau within 1 min; while type 3 units hardly slowed at all. Data
      from normal and diabetic subjects did not differ and were pooled. After 3 min at
      2 Hz, the percentage increases in latency were for type 1, 28.3 +/- 9.7 (n = 63
      units, mean +/- s.d.); for type 2, 5.2 +/- 1.6 (n = 14); and for type 3, 0.8 +/-
      0.5 (n = 5), with no overlap. After 3 min at 4 Hz, 58 % of type 1 units (but no
      type 2 or 3 units) blocked intermittently. Recovery of latency after stimulation
      was faster for type 2 than for type 1 units, but conduction velocities of the
      three types were similar. 3. Type 1 units were identified as nociceptors and 7
      type 2 units were identified as 'cold' fibres, activated by non-noxious cold,
      with no overlap in modality. None of the units tested was activated by weak
      mechanical stimuli or reflex sympathetic activation. 4. Spike waveforms were
      averaged for 18 type 1, 10 type 2 and 6 type 3 units. All units had predominantly
      triphasic action potentials with a major negative peak, but those of type 3 units
      were on average both smaller and briefer than those of type 1 and type 2 units.
      5. It is concluded that repetitive electrical stimulation reliably differentiates
      nociceptive from cold-specific C fibres innervating human hairy skin, as has
      previously been shown for the rat. Cold fibres can propagate impulses
      continuously at much higher rates than nociceptive fibres. The nature of the type
      3 units is unclear.

PMID- 10066907
TI  - Properties and functional roles of hyperpolarization-gated currents in guinea-pig
      retinal rods.
AB  - 1. The inward rectification induced by membrane hyperpolarization was studied in
      adult guinea-pig rods by the perforated-patch-clamp technique. 2. CsCl blocked
      the rectification observed in both voltage- and current-clamp recordings at
      voltages negative to -60 mV, while BaCl2 blocked the inward relaxation observed
      at voltages positive to -60 mV. The current activated at -90 mV had a low
      selectivity between sodium and potassium and reversed at -31.0 mV. 3. These
      observations suggest that two inward rectifiers are present in guinea-pig rods: a
      hyperpolarization-activated (Ih) and a hyperpolarization-deactivated (Ikx)
      current. The functional roles of Ih and Ikx were evaluated by stimulating rods
      with currents sinusoidally modulated in time. 4. Rods behave like bandpass
      amplifiers, with a peak amplification of 1.5 at about 2 Hz. For
      hyperpolarizations that mainly gate Ikx, amplification and phase shifts are fully
      accounted for by a rod membrane analogue model that includes an inductance. For
      hyperpolarizations that also gate Ih, a harmonic distortion became apparent. 5.
      Bandpass filtering and amplification of rod signals, associated with Ih and Ikx
      gating by membrane hyperpolarization, are strategically located to extend, beyond
      the limits imposed by the slow phototransductive cascade, the temporal resolution
      of signals spreading to the rod synapse.

PMID- 10066908
TI  - Adenosine inhibits the transfected Na+-H+ exchanger NHE3 in Xenopus laevis renal
      epithelial cells (A6/C1).
AB  - 1. Adenosine influences the vectorial transport of Na+ and HCO3- across kidney
      epithelial cells. However, its action on effector proteins, such as the Na+-H+
      exchanger NHE3, an epithelial brush border isoform of the Na+-H+ exchanger (NHE)
      gene family, is not yet defined. 2. The present study was conducted in Xenopus
      laevis distal nephron A6 epithelia which express both an apical adenosine
      receptor of the A1 type (coupled to protein kinase C (PKC)) and a basolateral
      receptor of the A2 type (coupled to protein kinase A (PKA)). The untransfected A6
      cell line expresses a single NHE type (XNHE) which is restricted to the
      basolateral membrane and which is activated by PKA. 3. A6 cell lines were
      generated which express exogenous rat NHE3. Measurements of side-specific pHi
      recovery from acid loads in the presence of HOE694 (an inhibitor with
      differential potency towards individual NHE isoforms) detected an apical
      resistant Na+-H+ exchange only in transfected cell lines. The sensitivity of the
      basolateral NHE to HOE694 was unchanged, suggesting that exogenous NHE3 was
      restricted to the apical membrane. 4. Stimulation of the apical A1 receptor with
      N 6-cyclopentyladenosine (CPA) inhibited both apical NHE3 and basolateral XNHE.
      These effects were mimicked by the addition of the protein kinase C (PKC)
      activator phorbol 12-myristate 13-acetate (PMA) and partially prevented by the
      PKC inhibitor calphostin C which also blocked the effect of PMA. 5. Stimulation
      of the basolateral A2 receptor with CPA inhibited apical NHE3 and stimulated
      basolateral XNHE. These effects were mimicked by 8-bromo-cAMP and partially
      prevented by the PKA inhibitor H89 which entirely blocked the effect of 8-bromo
      cAMP. 6. In conclusion, CPA inhibits rat NHE3 expressed apically in A6 epithelia
      via both the apical PKC-coupled A1 and the basolateral PKA-coupled A2 adenosine
      receptors.

PMID- 10066909
TI  - Effects of tetracaine on sarcoplasmic calcium release in mammalian skeletal
      muscle fibres.
AB  - 1. Single muscle fibres were dissociated enzymatically from the extensor
      digitorum communis muscle of rats. The fibres were mounted into a double Vaseline
      gap experimental chamber and the events in excitation-contraction coupling were
      studied under voltage clamp conditions in the presence and absence of the local
      anaesthetic tetracaine. 2. Changes in intracellular calcium concentration
      ([Ca2+]i) were monitored using the calcium sensitive dyes antipyrylazo III and
      fura-2 and the rate of calcium release (Rrel) from the sarcoplasmic reticulum
      (SR) was calculated. Tetracaine decreased the maximal attained [Ca2+]i and
      suppressed, in a dose-dependent manner, both the early peak and the steady level
      of Rrel in the voltage range examined. 3. The concentration dependence of the
      effects on the two kinetic components of Rrel were almost identical with a half
      effective concentration (K50) of 70 and 71 microM and a Hill coefficient (nH) of
      2.7 and 2.3 for the peak and the steady level, respectively. Furthermore, the
      drug did not alter the peak to steady level ratio up to a concentration (50
      microM) that caused a 35 +/- 5 % reduction in calcium release. Higher
      concentrations did suppress the ratio but the degree of suppression was voltage
      independent. 4. Tetracaine (50 microM) neither influenced the total available
      intramembrane charge nor altered its membrane potential dependence. It shifted
      the transfer function, the normalized SR permeability versus normalized charge to
      the right, indicating that similar charge transfer caused a smaller increase in
      SR permeability. 5. To explore the site of action of tetracaine further the
      ryanodine receptor (RyR) calcium release channel of the SR was purified and
      reconstituted into planar lipid bilayers. The reconstituted channel had a
      conductance of 511 +/- 14 pS (n = 8) in symmetric 250 mM KCl that was not
      affected by tetracaine. Tetracaine decreased the open probability of the channel
      in a concentration-dependent manner with K50 = 68 microM and nH = 1.5. 6. These
      experiments show that tetracaine suppresses SR calcium release in enzymatic
      isolated mammalian skeletal muscle fibres. This effect is due, presumably, to the
      decreased open probability of the RyR in the presence of the drug. Since both the
      inactivating peak and the steady level of Rrel were equally affected by
      tetracaine, our observations suggest that there is a tight coupling between these
      kinetic components of SR calcium release in mammalian skeletal muscle.

PMID- 10066910
TI  - Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR
      MDX mice is reduced by ion channel blockers.
AB  - 1. Single fibres were enzymatically isolated from interosseus muscles of
      dystrophic MDX mice, myotonic-dystrophic double mutant ADR-MDX mice and C57BL/10
      controls. The fibres were kept in cell culture for up to 2 weeks for the study of
      Ca2+ homeostasis and sarcolemmal Ca2+ permeability. 2. Resting levels of
      intracellular free Ca2+, determined with the fluorescent Ca2+ indicator fura-2,
      were slightly higher in MDX (63 +/- 20 nM; means +/- s.d.; n = 454 analysed
      fibres) and ADR-MDX (65 +/- 12 nM; n = 87) fibres than in controls (51 +/- 20 nM;
      n = 265). 3. The amplitudes of electrically induced Ca2+ transients did not
      differ between MDX fibres and controls. Decay time constants of Ca2+ transients
      ranged between 10 and 55 ms in both genotypes. In 50 % of MDX fibres (n = 68),
      but in only 20 % of controls (n = 54), the decay time constants were > 35 ms. 4.
      Bath application of Mn2+ resulted in a progressive quench of fura-2 fluorescence
      emitted from the fibres. The quench rate was about 2 times higher in MDX fibres
      (3.98 +/- 1.9 % min-1; n = 275) than in controls (2.03 +/- 1.4 % min-1; n = 204).
      The quench rate in ADR-MDX fibres (2.49 +/- 1.4 % min-1; n = 87) was closer to
      that of controls. 5. The Mn2+ influx into MDX fibres was reduced to 10 % by Gd3+,
      to 19 % by La3+ and to 47 % by Ni2+ (all at 50 microM). Bath application of 50
      microM amiloride inhibited the Mn2+ influx to 37 %. 6. We conclude that in
      isolated, resting MDX muscle fibres the membrane permeability for divalent
      cations is increased. The presumed additional influx of Ca2+ occurs through ion
      channels, but is well compensated for by effective cellular Ca2+ transport
      systems. The milder dystrophic phenotype of ADR-MDX mice is correlated with a
      smaller increase of their sarcolemmal Ca2+ permeability.

PMID- 10066911
TI  - Fluorescence changes of a label attached near the myosin active site on
      nucleotide binding in rat skeletal muscle fibres.
AB  - 1. Trinitrophenyl AMP (TNP-AMP) in the concentration range 10-300 microM induced
      an increase in fluorescence intensity at around 530 nm in skinned skeletal muscle
      fibres freshly obtained from rat psoas muscle. 2. The fluorescence intensity of
      the fibres depended on TNP-AMP concentration up to approximately 200 microM. The
      Kd of TNP-AMP binding to the muscle fibres was 38.0 +/- 8.4 microM (mean +/-
      s.d., n = 4 measurements) in three fibres. TNP-AMP fluorescence was readily
      washed out. 3. Various nucleotides affected the fluorescence of the fibres
      incubated in 20 microM TNP-AMP. MgATP (1 mM) and caged ATP (5 mM) reduced the
      fluorescence in 20 microM TNP-AMP by more than 40 % of the value measured in the
      absence of nucleotide. 4. When the fibres were stretched to almost no filament
      overlap, the extent of the quenching of the TNP-AMP (20 microM) fluorescence due
      to ATP binding was reduced by 14 %. This might be explained by assuming that the
      association of the thin filament affected the TNP-AMP fluorescence in muscle
      fibres. 5. The distance between the active site and the specific site for TNP was
      measured by the fluorescence resonance energy transfer between N
      methylanthraniloyl-ATP (Mant-ATP) bound to the active site and the TNP-AMP bound
      to the TNP-specific site in muscle fibres. The results showed that the distance
      between the two may be less than 2 nm. 6. It may be concluded that the
      fluorescence intensity at 530 nm in skinned muscle fibres in low concentrations
      of TNP-AMP changes directly reflecting the conformational state of the nucleotide
      binding region that is determined by the binding of nucleotides.

PMID- 10066912
TI  - Effects of targeted disruption of the mouse angiotensin II type 2 receptor gene
      on stress-induced hyperthermia.
AB  - 1. We have previously reported that brain angiotensin II type 2 receptors (AT2)
      contribute to immunological stress-induced hyperthermia (fever) in rats. Now, in
      mice, we report the effect of AT2 gene disruption on the hyperthermia induced by
      immunological (interleukin-1 (IL-1) injection) and non-immunological (saline
      injection or cage switch) stress. 2. AT2-deficient and control mice both showed
      typical circadian rhythmicity in body temperature and physical activity. During
      the latter half of the dark period, AT2-deficient mice exhibited a lower body
      temperature than the controls. 3. By comparison with the controls, AT2-deficient
      mice exhibited: (i) a significantly smaller hyperthermia after intraperitoneal
      (i.p.) injection of IL-1beta; (ii) significantly greater increases in body
      temperature and physical activity after i. p. saline; and (iii) a significantly
      greater hyperthermia (but a similar increase in activity) during cage-switch
      stress. 4. These results suggest that AT2, presumably in the brain, plays
      important roles in stress-induced hyperthermia in mice.

PMID- 10066913
TI  - Assessment of cardiac sympathetic regulation by respiratory-related arterial
      pressure variability in the rat.
AB  - 1. Mechanical ventilation evokes a corresponding arterial pressure variability
      (APV) which is decreased by beta-adrenoceptor antagonism. Therefore, in this
      study we set out to determine whether the respiratory-related APV can be used to
      assess cardiac sympathetic tone. 2. Computer-generated broad-band mechanical
      ventilation (0-3 Hz) was applied to Sprague-Dawley rats that had been
      anaesthetized with ketamine and paralysed with pancuronium. APV and its
      relationship to lung volume variability (LVV-APV) was systematically quantified
      with auto- or cross-spectral frequency domain analysis. 3. APV and LVV-APV
      transfer magnitudes between 0.5 and 1.5 Hz showed dose-dependent suppression by
      propranolol from 0.01 to 1 mg kg-1, while the static value of arterial pressure
      remained unchanged. Stroke volume variability, assessed by the use of a pulse
      contour method, exhibited a similar pattern of suppression by propranolol. In
      contrast, heart rate variability was not lowered with propranolol. 4. The effect
      of propranolol on respiratory-related APV persisted even in the presence of
      combined alpha-adrenoceptor and muscarinic receptor blockade by phentolamine and
      atropine. 5. The frequency range of 0.5-1.0 Hz was optimal for LVV-APV transfer
      magnitude to correlate with cardiac sympathetic tone. 6. We conclude that
      respiratory-related APV may provide a valid assessment of cardiac sympathetic
      regulation which is independent of parasympathetic and vascular sympathetic
      influences in ketamine-anaesthetized and positive pressure-ventilated rats.

PMID- 10066914
TI  - Restriction of placental and fetal growth in sheep alters fetal blood pressure
      responses to angiotensin II and captopril.
AB  - 1. We have measured arterial blood pressure between 115 and 145 days gestation in
      normally grown fetal sheep (control group; n = 16) and in fetal sheep in which
      growth was restricted by experimental restriction of placental growth and
      development (PR group; n = 13). There was no significant difference in the mean
      gestational arterial blood pressure between the PR (42.7 +/- 2.6 mmHg) and
      control groups (37.7 +/- 2.3 mmHg). Mean arterial blood pressure and arterial PO2
      were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16),
      but not in the PR group. 2. There were no changes in mean arterial blood pressure
      in either the PR or control groups in response to captopril (7.5 microg captopril
      min-1; PR group n = 7, control group n = 6) between 115 and 125 days gestation.
      After 135 days gestation, there was a significant decrease (P < 0.05) in the
      fetal arterial blood pressure in the PR group but not in the control group during
      the captopril infusion (15 microg captopril min-1; PR group n = 7, control group
      n = 6). 3. There was a significant effect (F = 14.75; P < 0.001) of increasing
      doses of angiotensin II on fetal diastolic blood pressure in the PR and control
      groups. The effects of angiotensin II were different (F = 8.67; P < 0.05) in the
      PR and control groups at both gestational age ranges. 4. These data indicate that
      arterial blood pressure may be maintained by different mechanisms in growth
      restricted fetuses and normally grown counterparts and suggests a role for the
      fetal renin-angiotensin system in the maintenance of blood pressure in growth
      restricted fetuses.

PMID- 10066915
TI  - Common 3 and 10 Hz oscillations modulate human eye and finger movements while
      they simultaneously track a visual target.
AB  - 1. A 10 Hz range centrally originating oscillation has been found to modulate
      slow finger movements and anticipatory smooth eye movements. To determine if an
      interaction or linkage occurs between these two central oscillations during
      combined visuo-manual tracking, frequency and coherence analysis were performed
      on finger and eye movements while they simultaneously tracked a visual target
      moving in intermittently visible sinusoidal patterns. 2. Two different
      frequencies of common or linked oscillation were found. The first, at 2-3 Hz, was
      dependent on visual feedback of target and finger tracking positions. The second,
      at around 10 Hz, still occurred when both target and finger positions were
      largely obscured, indicating that this common oscillation was generated
      internally by the motor system independent of visual feedback. Both 3 and 10 Hz
      oscillation frequencies were also shared by the right and left fingers if
      subjects used these together to track a visual target. 3. The linking of the 10
      Hz range oscillations between the eyes and finger was task specific; it never
      occurred when eye and finger movements were made simultaneously and
      independently, but only when they moved simultaneously and followed the target
      together. However, although specific for tracking by the eyes and fingers
      together, the linking behaviour did not appear to be a prerequisite for such
      tracking, since significant coherence in the 10 Hz range was only present in a
      proportion of trials where these combined movements were made. 4. The experiments
      show that common oscillations may modulate anatomically very distinct structures,
      indicating that single central oscillations may have a widespread distribution in
      the central nervous system. The task-specific manifestation of the common
      oscillation in the eye and finger suggests that such mechanisms may have a
      functional role in hand-eye co-ordination.

PMID- 10066916
TI  - Metabolism and inflammatory mediators in the peritendinous space measured by
      microdialysis during intermittent isometric exercise in humans.
AB  - 1. The metabolic processes that occur around the tendon during mechanical loading
      and exercise are undescribed in man. These processes are important for
      understanding the development of overuse inflammation and injury. 2. A
      microdialysis technique was used to determine interstitial concentrations of
      glycerol, glucose, lactate, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) as
      well as to calculate tissue substrate balance in the peritendinous region of the
      human Achilles tendon. Recovery of 48-62 % (range) at rest and 70-77 % during
      exercise were obtained for glycerol, glucose and PGE2. 3. Six young healthy
      humans were studied at rest, during 30 min of intermittent static plantar flexion
      of the ankle at a workload corresponding to individual body weight, and during 60
      min of recovery. Microdialysis was performed in both legs with simultaneous
      determination of blood flow by 133Xe washout in the same area, and blood sampling
      from the radial artery. 4. With exercise, the net release of lactate as well as
      of glycerol from the peritendinous space of the Achilles tendon increased 2-fold
      (P < 0.05). Furthermore a 100 % increase in interstitial concentration of PGE2
      and TXB2 was found, but it was only significant for TXB2(P < 0.05). As
      peritendinous blood flow increased 2- to 3-fold during intermittent static
      contractions, this indicates also that the output of these substances from the
      tissue increased during exercise. 5. This study indicates that both lipid and
      carbohydrate metabolism as well as inflammatory activity is accelerated in the
      peritendinous region of the human Achilles tendon with dynamic loading.

PMID- 10066917
TI  - Amplitude of the human soleus H reflex during walking and running.
AB  - 1. The objective of the study was to investigate the amplitude and modulation of
      the human soleus Hoffmann (H) reflex during walking and during running at
      different speeds. 2. EMGs were recorded with surface electrodes from the soleus,
      the medial and lateral head of the gastrocnemius, the vastus lateralis and the
      anterior tibial muscles. The EMGs and the soleus H reflex were recorded while
      walking on a treadmill at 4.5 km h-1 and during running at 8, 12 and 15 km h-1.
      3. The amplitudes of the M wave and the H reflex were normalized to the amplitude
      of a maximal M wave elicited by a supramaximal stimulus just after the H reflex
      to compensate for movements of the recording and stimulus electrodes relative to
      the nerve and muscle fibres. The stimulus intensity was set to produce M waves
      that had an amplitude near to 25 % of the maximal M wave measured during the
      movements. As an alternative, the method of averaging of sweeps in sixteen
      intervals of the gait cycle was applied to the data. In this case the amplitude
      of the H reflex was expressed relative to the maximal M wave measured whilst in
      the standing position. 4. The amplitude of the H reflex was modulated during the
      gait cycle at all speeds. During the stance phase the reflex was facilitated and
      during the swing and flight phases it was suppressed. The size of the maximal M
      wave varied during the gait cycle and this variation was consistent for each
      subject although different among subjects. 5. The peak amplitude of the H reflex
      increased significantly (P = 0.04) from walking at 4.5 km h-1 to running at 12
      and 15 km h-1 when using the method of correcting for variations of the maximal M
      wave during the gait cycle. The sweep averaging method showed a small but non
      significant decrease (P = 0. 3) from walking to running at 8 km h-1 and a small
      decrease with running speed (P = 0.3). The amplitude of the EMG increased from
      walking to running and with running speed. 6. The relatively large H reflex
      recorded during the stance phase in running indicates that the stretch reflex may
      influence the muscle mechanics during the stance phase by contributing to the
      motor output and enhancing muscle stiffness.

PMID- 10066918
TI  - Contributions of mitochondria to animal physiology: from homeostatic sensor to
      calcium signalling and cell death.
AB  - Over recent years, it has become clear that mitochondria play a central role in
      many key aspects of animal physiology and pathophysiology. Their central and
      ubiquitous task is clearly the production of ATP. Nevertheless, they also play
      subtle roles in glucose homeostasis, acting as the sensor for substrate supply in
      the transduction pathway that promotes insulin secretion by the pancreatic -cell
      and that modulates the excitability of the hypothalamic glucose-sensitive neurons
      involved in appetite control. Mitochondria may also act as sensors of
      availability of oxygen, the other major mitochondrial substrate, in the
      regulation of respiration. Mitochondria take up calcium, and the high opacity
      mitochondrial calcium uptake pathway provides a mechanism that couples energy
      demand to increased ATP production through the calcium-dependent upregulation of
      mitochondrial enzyme activity. Mitochondrial calcium accumulation may also have a
      substantial impact on the spatiotemporal dynamics of cellular calcium signals,
      with subtle differences of detail in different cell types. Recent work has also
      revealed the centrality of mitochondrial dysfunction as an irreversible step in
      the pathway to both necrotic and apoptotic cell death. This review looks at
      recent developments in these rapidly evolving areas of cell physiology in an
      attempt to draw together disparate areas of research into a common theme.

PMID- 10066919
TI  - Beta2-adrenergic receptor overexpression in the developing mouse heart: evidence
      for targeted modulation of ion channels.
AB  - 1. We studied the effect of overexpression of the beta2-adrenergic receptor
      (beta2-AR) in the heart on ion channel currents in single cells isolated from
      hearts of fetal and neonatal transgenic and wild-type mice. The beta2-AR
      transgene construct was under the control of the murine alpha-myosin heavy chain
      (alpha-MHC) promoter, and ion channel activity was measured at distinct
      developmental stages using whole-cell and perforated patch clamp techniques. 2.
      We found no change in L-type Ca2+ channel current (ICa) density in early
      embryonic stages (E11-13) of beta2-AR transgenic positive (TG+) mice, but
      significant increases in ICa density in intermediate (E14-16, 152 %) and late
      (E17-19, 173.7 %) fetal and neonatal (1 day post partum, 161 %) TG+ compared with
      transgenic negative (TG-) mice. This increase in ICa was accompanied by a
      negative shift in the peak of the current-voltage relationship in TG+ mice. 3.
      Transient (< 3 min) or prolonged (16-24 h) exposure of TG- neonatal stage
      myocytes to 8-Br-cAMP (300 microM) increased ICa density and caused a shift in
      the current-voltage relationship to a similar extent to that seen in TG+ mice. In
      TG+ myocytes, 8-Br-cAMP had no effect. Exposure of TG+ cells to Rp-cAMPS reversed
      both the shift in voltage dependence and reduced the peak current density
      observed in these myocytes. We concluded from these results that the L-type Ca2+
      channel is maximally modulated by cAMP-dependent protein kinase (PKA) in TG+ mice
      and that the alpha-MHC promoter is functional in the ventricle as early as
      embryonic day 14. 4. In contrast, we found that slow delayed rectifier K+
      channels were not changed significantly at any of the developmental stages
      studied by the overexpression of beta2-ARs compared with TG- mice. The
      sensitivity of murine slow delayed rectifier K+ channels to cAMP was tested by
      both transient and prolonged exposure to 8-Br-cAMP (300 microM), which increased
      the slow delayed rectifier K+ channel current (IK,s) density to a similar extent
      in both TG- and TG+ neonatal myocytes. In addition, we found that there was no
      difference in the concentration dependence of the response of ICa and IK,s to 8
      Br-cAMP. 5. Thus, overexpression of the beta2-AR in the heart results in distinct
      modulation of ICa, but not IK,s, and this is not due to differences in the 8-Br
      cAMP sensitivity of the two channels. Instead, these results are consistent with
      both compartmentalization of beta2-AR-controlled cAMP and distinct localization
      of L-type Ca2+ and slow delayed rectifier K+ channels. This cAMP is targeted
      preferentially to the L-type Ca2+ channel and is not accessible to the slow
      delayed rectifier K+ channel.

PMID- 10066920
TI  - Feedback inhibition of rat amiloride-sensitive epithelial sodium channels
      expressed in Xenopus laevis oocytes.
AB  - 1. Regulation of the amiloride-sensitive epithelial sodium channel (ENaC) is
      essential for the control of body sodium homeostasis. The downregulation of the
      activity of this Na+ channel that occurs when the intracellular Na+ concentration
      ([Na+]i) is increased is known as feedback inhibition. Although intracellular Na+
      is the trigger for this phenomenon, its cellular and molecular mediators are
      unknown. 2. We used the 'cut-open oocyte' technique to control the composition of
      the intracellular milieu of Xenopus oocytes expressing rat ENaCs to enable us to
      test several factors potentially involved in feedback inhibition. 3. The effects
      of perfusion of the intracellular space were demonstrated by an
      electromicrographic study and the time course of the intracellular solution
      exchange was established by observing the effect of intracellular pH: a decrease
      from pH 7.4 to 6.5 reduced the amiloride-sensitive current by about 40 % within 2
      min. 4. Feedback inhibition was observed in non-perfused oocytes when Na+ entry
      induced a large increase in [Na+]i. Intracellular perfusion prevented feedback
      regulation even though the [Na+]i was allowed to increase to values above 50 mM.
      5. No effects on the amiloride-sensitive current were observed after changes in
      the concentration of Na+ (from 1 to 50 mM), Ca2+ (from 10 to 1000 nM) or ATP
      (from nominally free to 1 or 5 mM) in the intracellular perfusate. 6. We conclude
      that feedback inhibition requires intracellular factors that can be removed by
      intracellular perfusion. Although a rise in [Na+]i may be the trigger for the
      feedback inhibition of the ENaC, this effect is not mediated by a direct effect
      of Na+, Ca2+ or ATP on the ENaC protein.

PMID- 10066921
TI  - ATP inhibition of a mouse brain large-conductance K+ (mslo) channel variant by a
      mechanism independent of protein phosphorylation.
AB  - 1. We investigated the effect of ATP in the regulation of two closely related
      cloned mouse brain large conductance calcium- and voltage-activated potassium
      (BK) channel alpha-subunit variants, expressed in human embryonic kidney (HEK
      293) cells, using the excised inside-out configuration of the patch-clamp
      technique. 2. The mB2 BK channel alpha-subunit variant expressed alone was
      potently inhibited by application of ATP to the intracellular surface of the
      patch with an IC50 of 30 microM. The effect of ATP was largely independent of
      protein phosphorylation events as the effect of ATP was mimicked by the non
      hydrolysable analogue 5'-adenylylimidodiphosphate (AMP-PNP) and the inhibitory
      effect of ATPgammaS was reversible. 3. In contrast, under identical conditions,
      direct nucleotide inhibition was not observed in the closely related mouse brain
      BK channel alpha-subunit variant mbr5. Furthermore, direct nucleotide regulation
      was not observed when mB2 was functionally coupled to regulatory beta-subunits.
      4. These data suggest that the mB2 alpha-subunit splice variant could provide a
      dynamic link between cellular metabolism and cell excitability.

PMID- 10066922
TI  - NH2-terminal fragments of the 130 kDa subunit of myosin phosphatase increase the
      Ca2+ sensitivity of porcine renal artery.
AB  - 1. The effects of the NH2-terminal fragments of M130, a 130 kDa regulatory
      subunit of smooth muscle myosin phosphatase, on contraction and myosin light
      chain phosphorylation were investigated in Triton X-100-permeabilized porcine
      renal artery. 2. Incubation of the permeabilized fibres with M1301-633 (a
      fragment containing amino acid residues 1-633) or M13044-633 enhanced the Ca2+
      induced contraction and shifted the [Ca2+]i-force relationship to the left (EC50
      of Ca2+: 330 nM, control, without fragment; 145 nM, M1301-633; 163 nM, M13044
      633). Pre-incubation for 1-3 h was needed for these long constructs. 3. M1301
      374, M130304-511 and M130297-374, i.e. relatively short constructs compared with
      M1301-633 and M13044-633, also induced leftward shifts of the [Ca2+]i-force
      relationship (EC50 of Ca2+: 65 nM, 72 nM and 180 nM, respectively). However,
      these required no pre-incubation. 4. Deletion of residues 304-374 from the most
      potent construct, M1301-374, abolished the Ca2+-sensitizing effect. 5. Wortmannin
      inhibited the enhancement of contraction induced by M130 fragments when added
      before contraction was initiated and partially inhibited the effects when added
      after steady-state contraction. 6. M1301-374 slowed the rate of relaxation in
      Ca2+-free medium. The time for 50 % relaxation with this fragment was 510 +/- 51
      s, compared with 274 +/- 14 s for control. 7. The levels of myosin light chain
      phosphorylation (22.4 %) and force (34. 5 %) obtained with 300 nM Ca2+ were
      increased by 3 microM M1301-374 to 35.7 and 92.2 %, respectively. However, M1301
      374 had no effect on the phosphorylation-force relationship. 8. In conclusion,
      the NH2-terminal M130 fragments containing residues 304-374 inhibited myosin
      phosphatase, increased myosin light chain phosphorylation and increased the Ca2+
      sensitivity of the contractile apparatus in permeabilized porcine renal artery.

PMID- 10066923
TI  - Role of Rho and Rho kinase in the activation of volume-regulated anion channels
      in bovine endothelial cells.
AB  - 1. We have studied the modulation of volume-regulated anion channels (VRACs) by
      the small GTPase Rho and by one of its targets, Rho kinase, in calf pulmonary
      artery endothelial (CPAE) cells. 2. RT-PCR and immunoblot analysis showed that
      both RhoA and Rho kinase are expressed in CPAE cells. 3. ICl,swell, the chloride
      current through VRACs, was activated by challenging CPAE cells with a 25 %
      hypotonic extracellular solution (HTS) or by intracellular perfusion with a
      pipette solution containing 100 microM GTPgammaS. 4. Pretreatment of CPAE cells
      with the Clostridium C2IN-C3 fusion toxin, which inactivates Rho by ADP
      ribosylation, significantly impaired the activation of ICl,swell in response to
      the HTS. The current density at +100 mV was 49 +/- 13 pA pF-1 (n = 17) in
      pretreated cells compared with 172 +/- 17 pA pF-1 (n = 21) in control cells. 5.
      The volume-independent activation of ICl,swell by intracellular perfusion with
      GTPgammaS was also impaired in C2IN-C3-pretreated cells (31 +/- 7 pA pF-1, n =
      11) compared with non-treated cells (132 +/- 21 pA pF-1, n = 15). 6. Activation
      of ICl,swell was pertussis toxin (PTX) insensitive. 7. Y-27632, a blocker of Rho
      kinase, inhibited ICl,swell and delayed its activation. 8. Inhibition of Rho and
      of Rho kinase by the above-described treatments did not affect the extent of cell
      swelling in response to HTS. 9. These experiments provide strong evidence that
      the Rho-Rho kinase pathway is involved in the VRAC activation cascade.

PMID- 10066924
TI  - Functional and molecular characterization of a volume-sensitive chloride current
      in rat brain endothelial cells.
AB  - 1. Volume-activated chloride currents in cultured rat brain endothelial cells
      were investigated on a functional level using the whole-cell voltage-clamp
      technique and on a molecular level using the reverse transcriptase-polymerase
      chain reaction (RT-PCR). 2. Exposure to a hypotonic solution caused the
      activation of a large, outward rectifying current, which exhibited a slight time
      dependent decrease at strong depolarizing potentials. The anion permeability of
      the induced current was I- (1.7) > Br- (1.2) > Cl- (1.0) > F- (0. 7) > gluconate
      (0.18). 3. The chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate
      (NPPB, 100 microM) rapidly and reversibly inhibited both inward and outward
      currents. The chloride transport blocker 4,4'-diisothiocyanatostilbene-2, 2'
      disulphonic acid (DIDS, 100 microM) also blocked the hypotonicity-induced current
      in a reversible manner. In this case, the outward current was more effectively
      suppressed than the inward current. The volume-activated current was also
      inhibited by the antioestrogen tamoxifen (10 microM). 4. The current was
      dependent on intracellular ATP and independent of intracellular Ca2+. 5.
      Activation of protein kinase C by phorbol 12,13-dibutyrate (PDBu, 100 nM)
      inhibited the increase in current normally observed following hypotonic
      challenge. 6. Extracellular ATP (10 mM) inhibited the current with a more
      pronounced effect on the outward than the inward current. 7. Verapamil (100
      microM) decreased both the inward and the outward hypotonicity-activated chloride
      current. 8. RT-PCR analysis was used to determine possible molecular candidates
      for the volume-sensitive current. Expression of the ClC-2, ClC-3 and ClC-5
      chloride channels, as well as pICln, could be shown at the mRNA level. 9. We
      conclude that rat brain endothelial cells express chloride channels which are
      activated by osmotic swelling. The biophysical and pharmacological properties of
      the current show strong similarities to those of ClC-3 channel currents as
      described in other cell types.

PMID- 10066925
TI  - Isosmotic modulation of Ca2+-regulated exocytosis in guinea-pig antral mucous
      cells: role of cell volume.
AB  - 1. Exocytotic events and changes of cell volume in mucous cells from guinea-pig
      antrum were examined by video-enhanced optical microscopy. 2. Acetylcholine (ACh)
      evoked exocytotic events following cell shrinkage, the frequency and extent of
      which depended on the ACh concentration. ACh actions were mimicked by ionomycin
      and thapsigargin, and inhibited by Ca2+-free solution and Ca2+ channel blockers
      (Ni2+, Cd2+ and nifedipine). Application of 100 microM W-7, a calmodulin
      inhibitor, also inhibited the ACh-induced exocytotic events. These results
      indicate that ACh actions are mediated by intracellular Ca2+ concentration
      ([Ca2+]i) in antral mucous cells. 3. The effects of ion channel blockers on
      exocytotic events and cell shrinkage evoked by ACh were examined. Inhibition of
      KCl release (quinine, Ba2+, NPPB or KCl solution) suppressed both the exocytotic
      events and cell shrinkage evoked by ACh. 4. Bumetanide (inhibition of NaCl entry)
      or Cl--free solution (increasing Cl- release and inhibition of NaCl entry) evoked
      exocytotic events following cell shrinkage in unstimulated antral mucous cells
      and caused further cell shrinkage and increases in the frequency of exocytotic
      events in ACh-stimulated cells. However, Cl--free solution did not evoke
      exocytotic events in unstimulated cells in the absence of extracellular Ca2+,
      although cell shrinkage occurred. 5. To examine the effects of cell volume on ACh
      evoked exocytosis, the cell volume was altered by increasing the extracellular K+
      concentration. The results showed that cell shrinkage increases the frequency of
      ACh-evoked exocytotic events and cell swelling decreases them. 6. Osmotic
      shrinkage or swelling caused the frequency of ACh-evoked exocytotic events to
      increase. This suggests that the effects of cell volume on ACh-evoked exocytosis
      under anisosmotic conditions may not be the same as those under isosmotic
      conditions. 7. In antral mucous cells, Ca2+-regulated exocytosis is modulated by
      cell shrinkage under isosmotic conditions.

PMID- 10066926
TI  - Sympathetic neuroeffector transmission in the rat anococcygeus muscle.
AB  - 1. When intracellular recordings were made from preparations of rat anococcygeus
      muscle, transmural nerve stimulation evoked noradrenergic excitatory junction
      potentials (EJPs) made up of two distinct components. Both components were
      abolished by either guanethidine or alpha-adrenoceptor antagonists, indicating
      that they resulted from the release of transmitter from sympathetic nerves and
      the subsequent activation of alpha-adrenoceptors. 2. The first component was
      associated with a transient increase in the intracellular concentration of
      calcium ions ([Ca2+]i) and a contraction. Although the second component was often
      associated with a long lasting increase in [Ca2+]i it was not associated with a
      contraction unless the second component initiated an action potential. 3. The
      increase in [Ca2+]i associated with the first component resulted from Ca2+
      release from an intracellular store and from entry of Ca2+ through voltage
      dependent Ca2+ channels. The increase in [Ca2+]i associated with the second
      component resulted only from the entry of Ca2+ through L-type Ca2+ channels (CaL
      channels). The depolarization associated with the initial increase in [Ca2+]i was
      abolished by reducing the external concentration of chloride ions ([Cl-]o),
      suggesting that it involved the activation of a Cl- conductance. 4. When the
      relationships between changes in [Ca2+]i, membrane depolarization and contraction
      produced by an increasing number of sympathetic nerve stimuli were determined in
      control, and caffeine- and nifedipine-containing solutions, it was found that an
      increase in [Ca2+]i recorded in nifedipine produced a larger contraction and
      larger membrane depolarization than did a similar increase in [Ca2+]i recorded in
      either control or caffeine-containing solutions. These observations indicate that
      Ca2+ released from stores more readily triggers contraction and membrane
      depolarization than does Ca2+ entry via CaL channels.

PMID- 10066927
TI  - Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+
      release events in rat ventricular myocytes.
AB  - 1. The time courses of Ca2+ current and Ca2+ spark occurrence were determined in
      single rat ventricular myocytes voltage clamped with patch pipettes containing
      0.1 microM fluo-3. Acquisition of line-scan images on a laser scanning confocal
      microscope was synchronized with measurement of Cd2+-sensitive Ca2+ currents. In
      most cells, individual Ca2+ sparks were observed by reducing Ca2+ current density
      with nifedipine (0.1-8 microM). 2. Ca2+ sparks elicited by depolarizing voltage
      clamp pulses had a peak [Ca2+] amplitude of 289 +/- 3 nM with a decay half-time
      of 20.8 +/- 0.2 ms and a full width at half-maximum of 1.40 +/- 0.03 microm (mean
      +/- s. e.m., n = 345), independent of the membrane potential. 3. The time between
      the beginning of a depolarization and the initiation of each Ca2+ spark was
      calculated and data were pooled to construct waiting time histograms. Exponential
      functions were fitted to these histograms and to the decaying phase of the Ca2+
      current. This analysis showed that the time constants describing Ca2+ current and
      Ca2+ spark occurrence at membrane potentials between -30 mV and +30 mV were not
      significantly different. At +50 mV, in the absence of nifedipine, the time
      constant describing Ca2+ spark occurrence was significantly larger than the time
      constant of the Ca2+ current. 4. A simple model is developed using Poisson
      statistics to relate macroscopic Ca2+ current to the opening of single L-type
      Ca2+ channels at the dyad junction and to the time course of Ca2+ spark
      occurrence. The model suggests that the time courses of macroscopic Ca2+ current
      and Ca2+ spark occurrence should be closely related when opening of a single L
      type Ca2+ channel initiates a Ca2+ spark. By comparison with the data, the model
      suggests that Ca2+ sparks are initiated by the opening of a single L-type Ca2+
      channel at all membrane potentials encountered during an action potential.

PMID- 10066928
TI  - Kinetics of inactivation and restoration from inactivation of the L-type calcium
      current in human myotubes.
AB  - 1. Inactivation and recovery kinetics of L-type calcium currents were measured in
      myotubes derived from satellite cells of human skeletal muscle using the whole
      cell patch clamp technique. 2. The time course of inactivation at potentials
      above the activation threshold was obtained from the decay of the current during
      15 s depolarizing pulses. At subthreshold potentials, prepulses of different
      durations, followed by +20 mV test pulses, were used. The time course could be
      well described by single exponential functions of time. The time constant
      decreased from 17.8 +/- 7.5 s at -30 mV to 1.78 +/- 0.15 s at +50 mV. 3.
      Restoration from inactivation caused by 15 s depolarization to +20 mV was slowed
      by depolarization in the restoration interval. The time constant increased from
      1.11 +/- 0.17 s at -90 mV to 7.57 +/- 2.54 s at -10 mV. 4. Restoration showed
      different kinetics depending on the duration of the conditioning depolarization.
      While the time constant was similar at restoration potentials of -90 and -50 mV
      after a 1 s conditioning prepulse, it increased with increasing prepulse duration
      at -50 mV and decreased at -90 mV. 5. The experiments showed that the rates of
      inactivation and restoration of the L-type calcium current in human myotubes were
      not identical when observed at the same potential. The results indicate the
      presence of more than one inactivated state and point to different voltage
      dependent pathways for inactivation and restoration.

PMID- 10066929
TI  - Release of Ca2+ from the sarcoplasmic reticulum increases mitochondrial [Ca2+] in
      rat pulmonary artery smooth muscle cells.
AB  - 1. The Ca2+-sensitive fluorescent indicator rhod-2 was used to measure
      mitochondrial [Ca2+] ([Ca2+]m) in single smooth muscle cells from the rat
      pulmonary artery, while simultaneously monitoring cytosolic [Ca2+] ([Ca2+]i) with
      fura-2. 2. Application of caffeine produced an increase in [Ca2+]i and also
      increased [Ca2+]m. The increase in [Ca2+]m occurred after the increase in
      [Ca2+]i, and remained elevated for a considerable time after [Ca2+]i had returned
      to resting values. 3. The protonophore carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP), which causes the mitochondrial membrane
      potential to collapse, markedly attenuated the increase in [Ca2+]m following
      caffeine application and also increased the half-time for recovery of [Ca2+]i to
      resting values. 4. Activation of purinoceptors with ATP also produced increases
      in both [Ca2+]i and [Ca2+]m in these smooth muscle cells. In some cells,
      oscillations in [Ca2+]i were observed during ATP application, which produced
      corresponding oscillations in [Ca2+]m and membrane currents. 5. This study
      provides direct evidence that Ca2+ release from the sarcoplasmic reticulum,
      either through ryanodine or inositol 1,4, 5-trisphosphate (InsP3) receptors,
      increases both cytosolic and mitochondrial [Ca2+] in smooth muscle cells. These
      results have potential implications both for the role of mitochondria in Ca2+
      regulation in smooth muscle, and for understanding how cellular metabolism is
      regulated.

PMID- 10066930
TI  - Mitochondrial regulation of the cytosolic Ca2+ concentration and the InsP3
      sensitive Ca2+ store in guinea-pig colonic smooth muscle.
AB  - 1. Mitochondrial regulation of the cytosolic Ca2+ concentration ([Ca2+]c) in
      guinea-pig single colonic myocytes has been examined, using whole-cell recording,
      flash photolysis of caged InsP3 and microfluorimetry. 2. Depolarization increased
      [Ca2+]c and triggered contraction. Resting [Ca2+]c was virtually restored some 4
      s after the end of depolarization, a time when the muscle had shortened to 50 %
      of its fully relaxed length. The muscle then slowly relaxed (t = 17 s). 3. The
      decline in the Ca2+ transient was monophasic but often undershot or overshot
      resting levels, depending on resting [Ca2+]c. The extent of the overshoot or
      undershoot increased with increasing peak [Ca2+]c. 4. Carbonyl cyanide m
      chlorophenyl hydrazone (CCCP; 5 microM), which dissipates the mitochondrial
      proton electrochemical gradient and therefore prevents mitochondrial Ca2+
      accumulation, slowed Ca2+ removal at high ( > 300 nM) but not at lower [Ca2+]c
      and abolished [Ca2+]c overshoots. Oligomycin B (5 microM), which prevents
      mitchondrial ATP production, affected neither the rate of decline nor the
      magnitude of the overshoot. 5. During depolarization, the global rhod-2 signal
      (which represents the mitochondrial matrix Ca2+ concentration, [Ca2+]m) rose
      slowly in a CCCP-sensitive manner during and for about 3 s after depolarization
      had ended. [Ca2+]m then slowly decreased over tens of seconds. 6. Inhibition of
      sarcoplasmic reticulum Ca2+ uptake with thapsigargin (100 nM) reduced the
      undershoot and increased the overshoot. 7. Flash photolysis of caged InsP3 (20
      microM) evoked reproducible increases in [Ca2+]c. CCCP (5 microM) reduced the
      magnitude of the [Ca2+]c transients evoked by flash photolysis of caged InsP3.
      Oligomycin B (5 microM) did not reduce the inhibition of the InsP3-induced Ca2+
      transient by CCCP thus minimizing the possibility that CCCP lowered ATP levels by
      reversing the mitochondrial ATP synthase and so reducing SR Ca2+ refilling. 8.
      While CCCP reduced the magnitude of the InsP3-evoked Ca2+ signal, the internal
      Ca2+ store content, as assessed by the magnitude of ionomycin-evoked Ca2+
      release, did not decrease significantly. 9. [Ca2+]c decline in smooth muscle,
      following depolarization, may involve mitochondrial Ca2+ uptake. Following InsP3
      evoked Ca2+ release, mitochondrial uptake of Ca2+ may regulate the local [Ca2+]c
      near the InsP3 receptor so maintaining the sensitivity of the InsP3 receptor to
      release Ca2+ from the SR.

PMID- 10066931
TI  - The cAMP transduction cascade mediates the PGE2-induced inhibition of potassium
      currents in rat sensory neurones.
AB  - 1. The role of the cyclic AMP (cAMP) transduction cascade in mediating the
      prostaglandin E2 (PGE2)-induced decrease in potassium current (IK) was
      investigated in isolated embryonic rat sensory neurones using the whole-cell
      patch-clamp recording technique. 2. Exposure to 100 microM chlorophenylthio
      adenosine cyclic 3', 5'-monophosphate (cpt-cAMP) or 1 microM PGE2 caused a slow
      suppression of the whole-cell IK by 34 and 36 %, respectively (measured after 20
      min), without a shift in the voltage dependence of activation for this current.
      Neither of these agents altered the shape of the voltage-dependent inactivation
      curve indicating that the suppression of IK did not result from alterations in
      the inactivation properties. 3. To determine whether the PGE2-mediated
      suppression of IK depended on activation of the cAMP pathway, cells were exposed
      to this prostanoid in the presence of the protein kinase A (PKA) inhibitor, PKI.
      The PGE2-induced suppression of IK was prevented by PKI. In the absence of PGE2,
      PKI had no significant effect on the magnitude of IK. 4. Results obtained from
      protocols using different conditioning prepulse voltages indicated that the
      extent of cpt-cAMP- and PGE2-mediated suppression of IK was independent of the
      prepulse voltage. The subtraction of control and treated currents revealed that
      the cpt-cAMP- and PGE2-sensitive currents exhibited little time-dependent
      inactivation. Taken together, these results suggest that the modulated currents
      may be delayed rectifier-like IK. 5. Exposure to the inhibitors of IK,
      tetraethylammonium (TEA) or 4-aminopyridine (4-AP), reduced the control current
      elicited by a voltage step to +60 mV by 40-50 %. In the presence of 10 mM TEA,
      treatment with cpt-cAMP did not result in any further inhibition of IK. In
      contrast, cpt-cAMP reduced IK by an additional 25-30 % in the presence of 1 mM 4
      AP. This effect was independent of the conditioning prepulse voltage. 6. These
      results establish that PGE2 inhibits an outward IK in sensory neurones via
      activation of PKA and are consistent with the idea that the PGE2-mediated
      sensitization of sensory neurones results, in part, from an inhibition of delayed
      rectifier-like IK.

PMID- 10066932
TI  - Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity
      in rabbit trachea.
AB  - 1. Average intracellular calcium concentration ([Ca2+]i) and ciliary beat
      frequency (CBF) were simultaneously measured in rabbit airway ciliated cells in
      order to elucidate the molecular events that lead to ciliary activation by
      purinergic stimulation. 2. Extracellular ATP and extracellular UTP caused a rapid
      increase in both [Ca2+]i and CBF. These effects were practically abolished by a
      phospholipase C inhibitor (U-73122) or by suramin. 3. The effects of
      extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by
      either GF 109203X or chelerythrine chloride, or when protein kinase A (PKA) was
      inhibited by RP-adenosine 3', 5'-cyclic monophosphothioate triethylamine (Rp
      cAMPS). 4. Activation of PKC by phorbol 12-myristate, 13-acetate (TPA) had little
      effect on CBF or on [Ca2+]i, while activation of PKA by forskolin or by dibutyryl
      cAMP led to a small rise in CBF without affecting [Ca2+]i. 5. Direct activation
      of protein kinase G (PKG) with dibutyryl-cGMP had a negligible effect on CBF when
      [Ca2+]i was at basal level. However, dibutyryl-cGMP strongly elevated CBF when
      [Ca2+]i was elevated either by extracellular ATP or by ionomycin. 6. The findings
      suggest that the initial rise in [Ca2+]i induced by extracellular ATP activates
      the NO pathway, thus leading to PKG activation. In the continuous presence of
      elevated [Ca2+]i the stimulated PKG then induces a robust enhancement in CBF. In
      parallel, activated PKG plays a central role in Ca2+ influx via a still
      unidentified mechanism, and thus, through positive feedback, maintains CBF close
      to its maximal level in the continuous presence of ATP.

PMID- 10066933
TI  - Thapsigargin inhibits a potassium conductance and stimulates calcium influx in
      the intact rat lens.
AB  - 1. An increase in lens cell calcium has long been associated with cortical
      cataract. Recently, it has been shown that thapsigargin induces a rise in lens
      cell calcium by release from endoplasmic reticulum stores. The effects of this
      rise on the optical and membrane characteristics of the lens were studied in the
      isolated rat lens. 2. The electrical characteristics of the isolated, perifused
      rat lens were measured using a two-internal microelectrode technique that permits
      measurement of plasma membrane conductance (Gm), membrane potential (Vm) and
      junctional conductance in the intact lens. 3. Thapsigargin (1 microM) induced a
      rapid overall depolarization of Vm that was accompanied by first a decrease and
      then an increase in Gm. 4. Replacing external Na+ with tetraethylammonium (TEA)
      abolished the decrease in Gm. However, a transient increase phase was still
      observed. 5. The changes in conductance were further characterized by measuring
      22Na+ and 45Ca2+ influxes into the isolated lens. Thapsigargin (1 microM) induced
      a transient increase in 45Ca2+, but did not affect Na+ influx. 6. The Ca2+
      channel blocker La3+ (10 microM) totally inhibited the thapsigargin-induced Ca2+
      influx. It also blocked the increase in Gm observed in control and in Na+-free
      TEA medium. In the absence of external calcium, thapsigargin induced a small
      depolarization in Vm. 7. These data indicate that thapsigargin induces both a
      decrease in K+ conductance and an increase in Ca2+ conductance. These probably
      result from release of stored Ca2+ and subsequent activation of store-operated
      Ca2+ channels (capacitative Ca2+ entry). 8. Thapsigargin application over the
      time course of these experiments (24 h) had no effect on junctional conductance
      or on the transparency of the lens.

PMID- 10066934
TI  - Inhibition of effects of flow on potassium permeability in single perfused frog
      mesenteric capillaries.
AB  - 1. We have investigated the effects of various potential inhibitors on flow
      dependent K+ permeability (PK) of single perfused mesenteric microvessels in
      pithed frogs. 2. Neither superfusion with a nitric oxide synthase inhibitor, NG
      monomethyl-L-arginine (10 or 100 micromol l-1), nor the addition of indomethacin
      (30 micromol l-1) to both perfusate and superfusate reduced the positive
      correlation between PK and flow velocity (U). 3. In the presence of agents known
      to raise intracellular levels of adenosine 3',5'-cyclic monophosphate
      (noradrenaline, 8-bromo-cAMP and a combination of forskolin and rolipram) the
      slope of the relation between PK and U was no longer significant, so that PK was
      no longer flow dependent. 4. These results confirm that the flow dependence of PK
      is a biological process and not an artefact of measurement and suggest a role for
      intracellular cAMP rather than nitric oxide or prostacyclin in the flow-dependent
      modulation of PK in frog mesenteric microvessels.

PMID- 10066935
TI  - A novel role for carbonic anhydrase: cytoplasmic pH gradient dissipation in mouse
      small intestinal enterocytes.
AB  - 1. The spatial and temporal distribution of intracellular H+ ions in response to
      activation of a proton-coupled dipeptide transporter localized at the apical pole
      of mouse small intestinal isolated enterocytes was investigated using
      intracellular carboxy-SNARF-1 fluorescence in combination with whole-cell
      microspectrofluorimetry or confocal microscopy. 2. In Hepes-buffered Tyrode
      solution, application of the dipeptide Phe-Ala (10 mM) to a single enterocyte
      reduced pHi locally in the apical submembranous space. After a short delay (8 s),
      a fall of pHi occurred more slowly at the basal pole. 3. In the presence of
      CO2/HCO3--buffered Tyrode solution, the apical and basal rates of acidification
      were not significantly different and the time delay was reduced to 1 s or less.
      4. Following application of the carbonic anhydrase inhibitor acetazolamide (100
      microM) in the presence of CO2/HCO3- buffer, addition of Phe-Ala once again
      produced a localized apical acidification that took 5 s to reach the basal pole.
      Basal acidification was slower than at the apical pole. 5. We conclude that acid
      influx due to proton-coupled dipeptide transport can lead to intracellular pH
      gradients and that intracellular carbonic anhydrase activity, by facilitating
      cytoplasmic H+ mobility, limits their magnitude and duration.

PMID- 10066936
TI  - Inhibition by adenosine receptor agonists of synaptic transmission in rat
      periaqueductal grey neurons.
AB  - 1. The actions of selective adenosine A1 and A2 receptor agonists were examined
      on synaptic currents in periaqueductal grey (PAG) neurons using patch-clamp
      recordings in brain slices. 2. The A1 receptor agonist 2-chloro-N
      cyclopentyladenosine (CCPA), but not the A2 agonist, 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680), inhibited
      both electrically evoked inhibitory (eIPSCs) and excitatory (eEPSCs) postsynaptic
      currents. The actions of CCPA were reversed by the A1 receptor antagonist 8
      cyclopentyl-1, 3-dipropylxanthine (DPCPX). 3. In the absence or presence of
      forskolin, DPCPX had no effect on eIPSCs, suggesting that concentrations of
      tonically released adenosine are not sufficient to inhibit synaptic transmission
      in the PAG. 4. CCPA decreased the frequency of spontaneous miniature action
      potential-independent IPSCs (mIPSCs) but had no effect on their amplitude
      distributions. Inhibition persisted in nominally Ca2+-free, high Mg2+ solutions
      and in 4-aminopyridine. 5. The CCPA-induced decrease in mIPSC frequency was
      partially blocked by the non-selective protein kinase inhibitor staurosporine,
      the specific protein kinase A inhibitor 8-para-chlorophenylthioadenosine-3',5'
      cyclic monophosphorothioate (Rp-8-CPT-cAMPS), and by 8-bromoadenosine cyclic
      3',5' monophosphate (8-Br-cAMP). 6. These results suggest that A1 adenosine
      receptor agonists inhibit both GABAergic and glutamatergic synaptic transmission
      in the PAG. Inhibition of GABAergic transmission is mediated by presynaptic
      mechanisms that partly involve protein kinase A.

PMID- 10066937
TI  - Quantal amplitude and quantal variance of strontium-induced asynchronous EPSCs in
      rat dentate granule neurons.
AB  - 1. Excitatory postsynaptic currents (EPSCs) were recorded from granule cells of
      the dentate gyrus in acute slices of 17- to 21-day-old rats (22-25 C) using
      tissue cuts and minimal extracellular stimulation to selectively activate a small
      number of synaptic contacts. 2. Adding millimolar Sr2+ to the external solution
      produced asynchronous EPSCs (aEPSCs) lasting for several hundred milliseconds
      after the stimulus. Minimally stimulated aEPSCs resembled miniature EPSCs
      (mEPSCs) recorded in the same cell but differed from them in ways expected from
      the greater range of dendritic filtering experienced by mEPSCs. aEPSCs had the
      same stimulus threshold as the synchronous EPSCs (sEPSCs) that followed the
      stimulus with a brief latency. aEPSCs following stimulation of distal inputs had
      a slower mean rise time than those following stimulation of proximal inputs.
      These results suggest that aEPSCs arose from the same synapses that generated
      sEPSCs. 3. Proximally elicited aEPSCs had a mean amplitude of 6.7 +/- 2.2 pA (+/-
      s.d., n = 23 cells) at -70 mV and an amplitude coefficient of variation of 0. 46
      +/- 0.08. 4. The amplitude distributions of sEPSCs never exhibited distinct
      peaks. 5. Monte Carlo modelling of the shapes of aEPSC amplitude distributions
      indicated that our data were best explained by an intrasite model of quantal
      variance. 6. It is concluded that Sr2+-evoked aEPSCs are uniquantal events
      arising at synaptic terminals that were recently invaded by an action potential,
      and so provide direct information about the quantal amplitude and quantal
      variance at those terminals. The large quantal variance obscures quantization of
      the amplitudes of evoked sEPSCs at this class of excitatory synapse.

PMID- 10066938
TI  - Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a
      comparison with metabolic inhibition.
AB  - 1. Hypoxia (PO2 < 5 mmHg) decreased vessel tone in isolated rat mesenteric
      arteries precontracted with either high [K+] or the thromboxane analogue U46619.
      This response was not altered by N-nitro-L-arginine (L-NA) and indomethacin. 2.
      Simultaneous measurement of pHi and tension showed that the decrease in vessel
      tone was accompanied by an intracellular acidification. Similar reductions in
      tone and pHi were observed with the metabolic inhibitors 2,4-dinitrophenol (DNP)
      and sodium azide. 3. The presence of the lactate transport inhibitor alpha-cyano
      4-hydroxy-cinnamic acid (CHC) increased the magnitude of the acidification and
      resulted in a significantly faster reduction in tone in response to hypoxia.
      Addition of CHC to normoxic tissues caused both a vasodilatation and a reduction
      of pHi. 4. A decrease in pHi induced on washout of ammonium chloride (NH4Cl)
      resulted in an increase in tone. 5. Relaxation to hypoxia or metabolic inhibition
      was unaffected when the change in pHi was neutralized by addition of the weak
      base trimethylamine (TMA). 6. It is concluded that severe hypoxia decreases tone
      in isolated rat mesenteric arteries by a mechanism which is independent of nitric
      oxide and prostaglandins. Both severe hypoxia and metabolic inhibition reduced
      pHi, although this does not appear to be contributing to the changes in tone
      observed.

PMID- 10066939
TI  - Nitric oxide release in penile corpora cavernosa in a rat model of erection.
AB  - 1. Nitric oxide (NO) levels were measured in the corpus cavernosum of urethane
      anaesthetized rats by using differential normal pulse voltammetry with carbon
      fibre microelectrodes coated with a polymeric porphyrin and a cation exchanger
      (Nafion). A NO oxidation peak could be recorded at 650 mV vs. a Ag-AgCl reference
      electrode every 100 s. 2. This NO signal was greatly decreased by the NO synthase
      inhibitor NG-nitro-L-arginine methyl ester (L-NAME), given by local and systemic
      routes, and enhanced by the NO precursor L-arginine. Treatment with L-arginine
      reversed the effect of L-NAME on the NO peak. 3. Both the NO signal and the
      intracavernosal pressure (ICP) were increased by electrical stimulation of
      cavernosal nerves (ESCN). However, the rise in the NO levels long outlived the
      rapid return to baseline of the ICP values at the end of nerve stimulation. 4.
      The ICP and the NO responses to ESCN were suppressed by local and systemic
      injections of L-NAME. Subsequent treatment with L-arginine of L-NAME-treated
      animals restored the NO signal to basal levels and the NO response to ESCN. The
      ICP response to ESCN was restored only in part by L-arginine. 5. The observed
      temporal dissociation between the NO and ICP responses could be accounted for by
      several factors, including the buffering of NO by the blood filling the
      cavernosal spaces during erection. 6. These findings indicate that an increased
      production of NO in the corpora cavernosa is necessary but not sufficient for
      maintaining penile erection and suggest a complex modulation of the NO-cGMP
      cavernosal smooth muscle relaxation cascade.

PMID- 10066940
TI  - In vitro simultaneous measurements of relaxation and nitric oxide concentration
      in rat superior mesenteric artery.
AB  - 1. The relationship between nitric oxide (NO) concentration measured with an NO
      specific microelectrode and endothelium-dependent relaxation was investigated in
      isolated rat superior mesenteric artery contracted with 1 microM noradrenaline.
      2. Acetylcholine (10 microM) induced endothelium-dependent simultaneous increases
      in luminal NO concentration of 21 +/- 6 nM, and relaxations with pD2 values and
      maximum of 6.95 +/- 0.32 and 97.5 +/- 0.7 % (n = 7), respectively. An inhibitor
      of NO synthase, N G-nitro-L-arginine (L-NOARG, 100 microM) inhibited the
      relaxations and increases in NO concentration induced by acetylcholine. 3.
      Oxyhaemoglobin (10 microM) reversed the relaxations and increases in NO
      concentrations induced by acetylcholine, S-nitroso-N-acetylpenicillamine (SNAP)
      and S-morpholino-sydnonimine (SIN-1), but not the relaxations induced with
      forskolin. Oxyhaemoglobin also decreased the NO concentration below baseline
      level. 4. In the presence of L-NOARG (100 microM), a small relaxation to
      acetylcholine (10 microM) of noradrenaline-contracted segments was still seen;
      oxyhaemogobin inhibited this relaxation and decreased the NO concentration by 14
      +/- 4 nM (n = 4). 5. The NO concentration-relaxation relationship for
      acetylcholine resembled that for SNAP and SIN-1 more than for authentic NO. Thus
      while 7-17 nM NO induced half-maximal relaxations in response to SNAP or SIN-1,
      378 +/- 129 nM NO (n = 4) was needed for half-maximal relaxation to authentic NO.
      6. The present study provides direct evidence that the relaxation of the rat
      superior mesenteric artery with the endothelium-dependent vasodilator
      acetylcholine is correlated to the endogeneous release of NO. The study also
      suggests that NO mediates the L-NOARG-resistant relaxations in this artery, and
      that there is a basal NO release.

PMID- 10066941
TI  - Spread of vasodilatation and vasoconstriction along feed arteries and arterioles
      of hamster skeletal muscle.
AB  - 1. In arterioles of the hamster cheek pouch, vasodilatation and vasoconstriction
      can spread via the conduction of electrical signals through gap junctions between
      cells that comprise the vessel wall. However, conduction in resistance networks
      supplying other tissues has received relatively little attention. In
      anaesthetized hamsters, we have investigated the spread of dilatation and
      constriction along feed arteries and arterioles of the retractor muscle, which is
      contiguous with the cheek pouch. 2. When released from a micropipette,
      acetylcholine (ACh) triggered vasodilatation that spread rapidly along feed
      arteries external to the muscle and arterioles within the muscle. Responses were
      independent of changes in wall shear rate, perivascular nerve activity, or
      release of nitric oxide, indicating cell-to-cell conduction. 3. Vasodilatation
      conducted without decrement along unbranched feed arteries, yet decayed markedly
      in arteriolar networks. Thus, branching of the conduction pathway dissipated the
      vasodilatation. 4. Noradrenaline (NA) or a depolarizing KCl stimulus evoked
      constriction of arterioles and feed arteries of the retractor muscle that was
      constrained to the vicinity of the micropipette. This behaviour contrasts sharply
      with the conduction of vasodilatation in these microvessels and with the
      conduction of vasoconstriction elicited by NA and KCl in cheek pouch arterioles.
      5. Focal electrical stimulation produced constriction that spread rapidly along
      feed arteries and arterioles. These responses were inhibited by tetrodotoxin or
      prazosin, confirming the release of NA along perivascular sympathetic nerves,
      which are absent from arterioles studied in the cheek pouch. Thus, sympathetic
      nerve activity co-ordinated the contraction of smooth muscle cells as effectively
      as the conduction of vasodilatation co-ordinated their relaxation. 6. In the
      light of previous findings in the cheek pouch, the properties of vasoconstriction
      and vasodilatation in feed arteries and arterioles of the retractor muscle
      indicate that substantive differences can exist in the nature of signal
      transmission along microvessels of tissues that differ in structure and function.

PMID- 10066942
TI  - Firing properties of single vasoconstrictor neurones in human subjects with high
      levels of muscle sympathetic activity.
AB  - 1. Single-unit recordings were made from 19 postganglionic muscle vasoconstrictor
      axons via tungsten microelectrodes in the peroneal nerve in seven healthy
      subjects with many multi-unit sympathetic discharges at rest ('high group', 75 +/
      5 multi-unit bursts per 100 heart beats, mean +/- s.e.m.). The results were
      compared with previous data from 14 units in subjects with 21 +/- 2 multi-unit
      bursts per 100 heart beats ('low group'). 2. In the 'high group' the units fired
      spontaneously in 35 +/- 4 % of all cardiac intervals. One unit only ever fired
      once per cardiac interval, 14 units (74 %) generated maximally two to three
      spikes, and four units (21 %) up to four to five spikes. Of those cardiac
      intervals in which a unit fired, a single spike occurred in 78 %, two spikes in
      18 %, three spikes in 4 % and four spikes in less than 1 % of cardiac intervals.
      Measured as the inverse of all interspike intervals, the mean rate was 0.33 +/-
      0.04 Hz and the mean intraburst frequency 22.2 +/- 1.6 Hz. Most results were
      similar to those in the 'low group', but in the 'low group' heart rate was higher
      (64.5 vs. 50.4 beats min-1) and mean firing frequency was higher (0.49 +/- 0.06
      Hz). 3. During increases of multi-unit burst activity evoked by sustained
      inspiratory-capacity apnoea the firing probability of nine units in the 'high
      group' increased from 33 +/- 6 to 56 +/- 3 % of the cardiac intervals.
      Simultaneously, the incidence of single spikes decreased and the incidence of
      multiple spikes per cardiac interval increased, resulting in an increase of mean
      firing frequency from 0. 23 +/- 0.04 Hz at rest to 1.04 +/- 0.14 Hz during the
      apnoea. 4. We conclude that single muscle vasoconstrictor neurones usually fire
      only a solitary spike during sympathetic bursts both in subjects with a high and
      in subjects with a low number of bursts at rest. Presumably, differences in the
      numbers of bursts are due mainly to differences in firing probability and
      recruitment of sympathetic fibres. During acute increases of multi-unit activity,
      both increases in discharge frequency and recruitment of additional neurones
      contribute to the increased intensity of an individual sympathetic burst.

PMID- 10066944
TI  - [Phase III trials in oncology].
AB  - The randomised trial is the best context for the assessment of any new molecule
      in oncology. The authors emphasize the methodological aspects of randomised
      trials and suggest strategies to be adopted in phase III trials, based on the
      newly orthodox concept of evidence-based medicine, while underscoring the need
      for context specific adaptations to increase relevance and specificity of sought
      endpoints, including other means of controlling adequately the clinical
      experiment without randomization (patient as his own control models). The authors
      also suggest certain strategic changes. For example, restrictive but relevant
      eligibility criteria may help decrease the number of patients needed without
      compromising statistical power as well as other strategies aimed at proving the
      efficacy of a new molecule without carrying out large trials, which are too long
      and costly.

PMID- 10066943
TI  - Respiratory and cardiac modulation of single sympathetic vasoconstrictor and
      sudomotor neurones to human skin.
AB  - 1. The firing of single sympathetic neurones was recorded via tungsten
      microelectrodes in cutaneous fascicles of the peroneal nerve in awake humans.
      Studies were made of 17 vasoconstrictor neurones during cold-induced cutaneous
      vasoconstriction and eight sudomotor neurones during heat-induced sweating.
      Oligounitary recordings were obtained from 8 cutaneous vasconstrictor and 10
      sudomotor sites. Skin blood flow was measured by laser Doppler flowmetry, and
      sweating by changes in skin electrical resistance within the innervation
      territory on the dorsum of the foot. 2. Perispike time histograms revealed
      respiratory modulation in 11 (65 %) vasoconstrictor and 4 (50 %) sudomotor
      neurones. After correcting for estimated conduction delays, the firing
      probability was higher in inspiration for both classes of neurone. Measured from
      the oligounitary recordings, the respiratory modulation indices were 67. 7 +/-
      3.9 % for vasoconstrictor and 73.5 +/- 5.7 % for sudomotor neurones (means +/-
      s.e.m.). As previously found for sudomotor neurones, cardiac rhythmicity was
      expressed by 7 (41 %) vasoconstrictor neurones, 5 of which showed no significant
      coupling to respiration. Measured from the oligounitary records, the cardiac
      modulation of cutaneous vasoconstrictor activity was 58.6 +/- 4.9 %, compared
      with 74.4 +/- 6.4 % for sudomotor activity. 3. Both vasoconstrictor and sudomotor
      neurones displayed low average firing rates (0.53 and 0.62 Hz, respectively). The
      percentage of cardiac intervals in which units fired was 38 % and 35 %,
      respectively. Moreover, when considering only those cardiac intervals when a unit
      fired, vasoconstrictor and sudomotor neurones generated a single spike 66 % and
      67 % of the time. Rarely were more than four spikes generated by a single
      neurone. 4. We conclude that human cutaneous vasoconstrictor and sudomotor
      neurones share several properties: both classes contain subpopulations that are
      modulated by respiration and/or the cardiac cycle. The data suggest that the
      intensity of a multi-unit burst of vasoconstrictor or sudomotor impulses is
      probably governed primarily by firing incidence and the recruitment of additional
      neurones, rather than by an increase in the number of spikes each unit
      contributes to a burst.

PMID- 10066945
TI  - [Angiogenesis and endocrine tumors].
AB  - Endocrine tumors are characteristically hypervascularized. This property recalls
      that of normal endocrine tissues, which possess a dense and specialized capillary
      network. The cellular and molecular mechanisms of the angiogenesis process
      associated with endocrine tumorigenesis are poorly known. Most normal endocrine
      cells constituvely express high levels of angiogenic factors, such as VEGF, which
      likely play an important role in the development of the characteristic vascular
      architecture of normal endocrine tissues. Clinical and experimental data suggest
      that a surexpression of such angiogenic factors is unlikely to be involved in the
      induction of the angiogenic process associated with endocrine tumorigenesis. In
      contrast, according to some experimental observations, the loss of endocrine
      specific anti-angiogenic factors may be required for the initiation of the
      angiogenic process and the transition from endocrine hyperplasia to endocrine
      neoplasia. Such inhibitory factors remain to be identified and characterized. A
      better understanding of the mechanisms of angiogenesis in endocrine tumors is
      important for the delineation of novel therapeutic strategies.

PMID- 10066946
TI  - [Integrins and metalloproteinases: an efficient collaboration in the invasive
      process].
AB  - During the invasive process, tumor cells must move through the extracellular
      matrix. They have to adhere to the extracellular matrix components, then
      proteolyse them and migrate on their fragments. This implicates integrins and
      proteinases, namely metalloproteinases. Numerous experiments which had been
      performed on various models, namely malignant melanomas proved that integrins
      have a major role in the transduction of signals from the outside to the inside
      of the cells, such signals enhancing the expression of the metalloproteinases or,
      in the contrary, inhibiting it. The modifications of this expression are
      dependent of extracellular matrix components and may be induced by the linking of
      specific antibodies to integrins. In some instances, the integrins localized on
      the tumor cell surface may act as receptors for extracellular matrix proteins and
      metalloproteinases at once, that may give to tumor cells an higher efficiency in
      the invasive process. Such mechanisms may result in interesting clinical
      perspectives for the control of metalloproteinases regulation in pathological
      processes.

PMID- 10066947
TI  - [Standards, options and recommendations (SOR) for diagnosis, treatment and follow
      up of osteosarcoma. Groupe de travail SOR].
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 outcome 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 clinical practice guidelines according to the
      definitions of Standards, Options and Recommendations for the clinical care of
      osteosarcoma in children and adult. METHODS: Data have been identified by
      literature search using Medline (1985-december 1998) and the expert groups
      personal reference lists. The main criteria considered were incidence, risk
      factors, prognostic factors and efficacy of treatment. Once the guidelines were
      defined, the document was submitted for review to 27 national and international
      independent reviewers, and to the medical committees of the 20 French Cancer
      Centres and, in particular, the 4 which have particular expertise in pediatric
      cancer management. RESULTS: The main recommendations for osteosarcoma management
      are that: 1) the clinical diagnosis is based on appropriate clinical and
      radiological findings; 2) the final diagnosis is pathological and the biopsy
      should be performed by the surgeon who will subsequently perform the definitive
      surgery; 3) surgical biopsy must be of adequate size and performed by an
      experienced surgeon; 4) the therapeutic strategy for osteosarcoma is based on
      surgery with neoadjuvant and adjuvant chemotherapy given in experienced centres.
      Inclusion of high dose methotrexate is recommended for children, and the dose of
      methotrexate must be adapted for adults. Inclusion of children in SFOP protocols
      and adults in EORTC and FNCLCC clinical trials is recommended; 5) treatment of
      metastatic osteosarcoma is based on chemotherapy and surgery to lung metastases
      which may be curative. Amputation is rarely appropriate. Inclusion of children in
      SFOP and of adult in EORTC and FNCLCC clinical trials for metastatic osteosarcoma
      is recommended; 6) at the present time, there are no clear data on which to base
      guidelines for timing and duration of follow-up studies in this condition.

PMID- 10066948
TI  - [Estimation of the incidence of eight malignant tumours in France, on the basis
      of health insurance's statistics].
AB  - This work has for aim to suggest coefficients of adjustment applicable to the
      statistics of malignant tumours refunded through the health insurance as long
      term diseases. Those coefficients would allow to evaluate the morbidity rate of
      cancer in the general population in France. To reach this target, we compared the
      figures of health insurance to those of the registers of cancers in six french
      departments, after we made the necessary adjustments to make the comparison
      possible. We showed that, for each cancer, the coefficient of adjustment is equal
      to the median of the relative differences that we noticed between the figures of
      the registers and those of the health insurance. We calculated the adjustment
      coefficients for bladder cancers (1.07), colon-rectum cancers (1.36), womb
      cancers (1), kidney cancers (0.83), lung cancers (1.33), oesophagus cancers
      (1.56) and prostate cancers (1.37). The comparison between the incidences
      adjusted on the basis of the figures of the health insurance, the incidences
      estimated by the Inserm and those released in the literature allowed us to
      confirm the validity of the coefficient we propose, except for the kidney cancer
      and the lung cancer by women, for whom we can't make any conclusions. Our work
      shows that the statistics of health insurance builds up a basis of information
      that can be used to study the morbidity rate of some malignant tumours in France.

PMID- 10066949
TI  - [Conservative treatment of multifocal breast cancer: a comparative study].
AB  - Conservative treatment of multifocal breast cancer is still very controversial.
      This retrospective study concerns 56 patients with stage I or II multifocal
      breast cancer who underwent conservative treatment at the Institut Curie from
      January 1983 to December 1989. These patients (group 1) were matched with 132
      patients with multifocal lesions treated by mastectomy (group 2). Surgical
      treatment consisted of a single wide lumpectomy followed by external
      radiotherapy. Adjuvant systemic therapy and regional nodal irradiation were
      administered as indicated by current protocols. The actuarial 5-year overall
      survival rate was 94% 6 in group 1, and 90% 6 in group 2 (NS). The actuarial 5
      year ipsilateral breast recurrence rate was 11% 8 in group 1, and 11% 5 in group
      2 (NS). In group 1 patients, the ipsilateral breast recurrence rate was related
      neither to type of multifocality nor to presence of intra ductal breast
      carcinoma, nodal status, tumor margins, radiotherapy boost, or distance between
      tumors. Consequently, conservative treatment of multifocal breast cancers which
      can be completely removed by a single lumpectomy seems, when technically
      feasible, an alternative to mastectomy.

PMID- 10066950
TI  - [Neoadjuvant chemotherapy FEC-HD in locally advanced breast cancer].
AB  - The tolerance and the clinical and histological efficacy of a neoadjuvant
      chemotherapy FEC-HD including hematopoietic growth factors have been studied in
      40 patients with stade II or III breast cancer between February 1991 and February
      1997. Four courses were given, every 21 days, with 5-fluorouracil (750 mg/m2/day
      D1 to D4 by continuous infusion), epirubicin (35 mg/m2/day D2 to D4) and
      cyclophosphamide (400 mg/m2/day D2 to D4) with G-CSF (5 mug/kg/day D6 to D15).
      The surgery was performed 3 or 4 weeks after the end of the chemotherapy. All
      patients had radiotherapy. The neoadjuvant chemotherapy induced 37.5% CR, 45% PR,
      and 15% SD. In 40% of the patients, the surgery was conservative. An histological
      CR was obtained in 15% with no axillary involvement one time out of two. There
      was intraductal carcinoma without invasive carcinoma in 7.5%. There was no
      differences between the response of inflammatory and non inflammatory tumors. One
      hundred and fifty-eight courses have been delivered. A grade 3 or 4
      leuconeutropenia, anemia and thrombopenia have been observed in respectively
      34.6%, 6.3% and 8.8% of the courses. A grade 3 or 4 mucositis has been noticed in
      2.5% of the courses. A febrile granulocytopenia has occurred in 3.8% of the
      courses. The median survival without metastatic progression was 48 months and the
      median overall survival was not achieved. In stade II and III breast cancer,
      neoadjuvant chemotherapy with FEC-HD obtains an important histological response
      with an acceptable toxicity. The role of the dose-intensity increase on survival
      remains to be determined.

PMID- 10066951
TI  - [Clinical benefits of stabilization after second-line chemotherapy in patients
      with metastatic colorectal cancer].
AB  - New innovative cytotoxic agents have proven active for treating patients with
      metastatic cancer who have failed first line 5FU based therapy, with sizeable
      objective response rates and a much higher rate of stabilization. The benefit of
      stabilization has not yet been well evaluated. A prospective multicentric study
      was carried out with 80 patients treated by second line chemotherapy for
      metastatic colorectal cancer. Tumor assessment and symptomatic status were
      reported at each cycle with a 4-month follow-up, allowing dynamic patient
      categorization per health state associated with the treatment. It appears that
      patients who are stabilized by chemotherapy have a quality of life profile
      comparable to that of responders, as opposed to patients with progressive
      disease. More patients experience improvement or stabilization of their quality
      of life, while they are stabilized versus progressive patients. Average number of
      days in hospital and hospital costs are cut down by three during stabilization as
      opposed to progressive disease. These results provide evidence that disease
      stabilization brings benefit to patients and reduces hospitalization.

PMID- 10066952
TI  - [Compassionate use of gemcitabine in advanced pancreatic cancer: a French
      multicentric study].
AB  - Advanced-stage surgically unresectable adenocarcinoma of the pancreas is highly
      lethal. Attempts to improve this survival with chemotherapy were dismal, until
      gemcitabin was shown to be clinically beneficial and to modestly improve
      survival. We started an open multicentric compassionate study of gemcitabine in
      advanced adenocarcinoma of the pancreas to assess those benefits. Of 74 patients
      who were enrolled, 46 were assessable for tumoral response (2 partial response,
      18 stable disease, 24 progressing disease). A clinical benefit was obtained in
      48% of assessable patients. Myelotoxicity, nausea and vomiting were the major
      side effect. The median event-free and overall survivals from study inclusion
      were 2. 5 and 5 months respectively. This study confirms that gemcitabine can be
      effective even in patients with pretreated advanced adenocarcinoma of the
      pancreas.

PMID- 10066953
TI  - Intercellular IgA dermatosis.
AB  - We report three cases of intercellular IgA dermatosis (IAD) and review the
      literature. IAD is a spectrum of vesiculobullous or vesiculopustular diseases
      mediated by intercellular IgA deposition. The clinical picture may vary from a
      vesiculopustular eruption with centrifugal evolution mainly involving the trunk
      and extremities, to the typical picture of classic pemphigus variants (foliaceus,
      vegetans). Histologically, infiltrating polymorphonuclear cells (mainly
      neutrophils) are observed in the epidermis with formation of pustules and bullae
      at various levels. However cases with typical histological features of pemphigus
      (variants) are described. Direct immunofluorescence on perilesonal skin typically
      displays intercellular IgA deposition at different levels or throughout the
      epidermis and indirect immunofluorescence often detects low levels of circulating
      antibodies. The disease has been repeatedly reported in association with
      monoclonal IgA gammopathy. Most cases respond to dapsone. In some cases IgA is
      directed against known pemphigus antigens whereas their targets in other cases
      are newly discovered antigens (105 kD, 115 kD, 120 kD). We observe a
      heterogeneity within the clinical, histological and immunological characteristics
      of the disease. Many reported cases feature various combinations of these
      characteristics. We therefore consider IAD as a disease spectrum with IgA
      pemphigus (clinical and histological pemphigus) at one end and intercellular IgA
      vesiculopustular dermatosis at the other end.

PMID- 10066954
TI  - Immediate pigment darkening: description, kinetic and biological function.
AB  - Immediate pigment darkening (IPD) is a transitory darkening of the skin observed
      after UVA exposure. The melanocytic system is implicated in its development.
      Indeed, it involves structural changes in melanocytes and keratinocytes and a
      chemical modification of pre-existing melanin. Darkening intensity is maximum
      immediately after exposure and decreases rapidly. The maximum efficiency
      wavelength for induction of IPD is around 340 nm. The phenomenon is inhibited by
      oxygen deprivation. Dose-response curves are linear for doses above 4 J/cm2.
      Minimum dose for induction of IPD (MIPDD) varies with the subject according to
      phototype, melanotype and skin color. The best criterion for predicting MIPDD
      seems to be chromametrically determined skin color. The biological role of IPD
      remains poorly understood; several hypotheses are discussed.

PMID- 10066955
TI  - Treatment of scabies with ivermectin.
AB  - The authors report six new cases of patients suffering from severe infestation
      with the mite sarcoptes scabiei, treated with ivermectin, currently the only oral
      therapy available for this disease. Each patient received 200 mug/kg of
      ivermectin, taken as single dose. No topical therapy was undertaken, except for
      topical treatment with emollient, as needed. The drug was very effective in all
      cases, easy to use, safe, and particularly useful in those patients with
      secondary eczematisation and escoriations, for whom the topical treatments are
      irritant and less well tolerated.

PMID- 10066956
TI  - Immunohistochemical study of the early histopathologic changes occurring in
      trauma-injured skin of psoriatic patients.
AB  - In the present study we have investigated the early histopathologic as changes
      occurring in the Koebner reaction induced by traumatic injury in uninvolved skin
      of 23 psoriatic and 7 non-psoriatic control patients. A punch biopsy of the
      injured area was performed after 2-3 (15 cases) or 7 days (8 cases). As a trauma,
      instead of the classic sellotape stripping, needle scarification was used. A
      peculiar histological feature of the skin biopsies of 13/23 psoriatic patients
      (56%) was a keratinocyte hyperplasia leading to a "papillary" projection into the
      upper dermis, just beneath the scarification. The papillary projection was
      associated with the expression of intercellular adhesion molecule-1 (ICAM-1) in
      the keratinocytes of 9/13 cases (70%) and with the presence of peri-papillary
      aggregates of CD68+ cells in 10/13 cases. In the upper dermis, tenascin was
      markedly expressed in 12/13 cases. Moreover, in one third of the cases, just
      beneath the scarification, there was reabsorption of the epidermal basal membrane
      as documented by a marked reduction of collagen type IV and laminin content.
      These histopathological alterations were detected in 6/15 psoriatic patients
      whose skin biopsy was taken 2-3 days after scarification, in 7/8 after 7 days,
      and in only 1/7 non psoriatic controls. Our results indicate that needle
      scarification can be a suitable method to study the early events occurring in
      trauma injured psoriatic skin.

PMID- 10066957
TI  - Macrophage marker 27E10 on human keratinocytes helps to differentiate discoid
      lupus erythematosus and Jessner's lymphocytic infiltration of the skin.
AB  - Chronic inflammatory discoid lupus erythematosus (DLE) and Jessner's lymphocytic
      infiltration of the skin (LIS) are both characterized by dermal infiltrates of
      activated T lymphocytes. However, an inflammatory involvement of the epidermis is
      only found in DLE. We therefore compared the phenotypic properties of the
      keratinocytes using immunohistochemical stainings of biopsies from typical DLE
      and LIS. Keratinocytes failed to express HLA-DR in LIS and surprisingly also in
      DLE. The adhesion molecule ICAM-1 was only expressed in DLE, with focal staining
      of the basal keratinocytes in close association with intraepidermal lymphocytes.
      The monoclonal antibody 27E10, a distinct marker for macrophage activation and
      differentiation, revealed a strong band-like labelling of the suprabasal and
      upper keratinocytes in DLE. In contrast, no epidermal expression of this
      biologically active heterodimer of the calcium-binding proteins MRP-8 and MRP-14
      was found in LIS. The staining patterns provide a new method to differentiate DLE
      and LIS by immunohistochemistry and suggest a distinct type of keratinocyte
      activation and differentiation in DLE which would in turn mediate epidermal T
      cell infiltration.

PMID- 10066958
TI  - Pronounced perifollicular lymphocytic infiltrates in alopecia areata are
      associated with poor treatment response to diphencyprone.
AB  - Some authors have reported that severe destruction of follicular structures and
      even scarring patterns occur in those patients with alopecia areata (AA) who fail
      to respond to topical immunotherapy with contact sensitizers, such as
      diphencyprone (DCP). Other studies, however, gave contradictory results.
      Therefore, we re-examined histopathological changes in scalp samples obtained
      from 85 patients with severe alopecia areata before initiation of DCP treatment
      (40 responders and 45 non-responders in terms of hair regrowth after DCP
      treatment). The following parameters were evaluated: i) perifollicular
      lymphocytic infiltration; ii) perifollicular fibrosis, and iii) miniaturized hair
      follicles. No difference between responders and non-responders could be observed
      in the degree of miniaturization of hair follicles and proliferation of
      perifollicular fibrous tissue. In neither group was there any evidence of
      scarring or severe follicular destruction. 18 non-responders but only 6
      responders showed a very dense perifollicular lymphocytic infiltration. In
      contrast, a particularly scarce infiltrate was seen in 9 non-responders and in 19
      responders. We conclude that non-responders to topical sensitizers tend to have
      rather pronounced inflammatory reactions with dense perifollicular lymphocytic
      infiltrates.

PMID- 10066959
TI  - Epidermal nuclear CIq deposits in a patient with amyopathic dermatomyositis.
AB  - We report a case of amyopathic dermatomyositis, in which C1q deposits on the
      epidermal nucleus were immunohistologically found as well as Ig deposits at the
      dermoepidermal junction (DEJ). Direct immunofluorescence (IF) examination of
      infiltrated erythematous lesions revealed C1q deposits on the epidermal nucleus
      and fibrinogen at the DEJ, and examination of hyperkeratotic erythematous lesions
      showed linear deposits of Ig G and Ig A at the DEJ but not in the nuclei of
      epidermal cells. The authors discuss the direct in vivo interaction between
      nucleus and immunoreactants in dermatomyositis.

PMID- 10066960
TI  - Angiosarcoma. A rare secondary malignancy after breast cancer treatment.
AB  - Life-saving mastectomy and radiation therapy are established in the treatment of
      early stage breast cancer. Angiosarcoma, i.e. malignant angioendothelioma, is a
      rare tumor which can develop after several years of such treatment. The number of
      post-operative and post-irradiation angiosarcomas has increased in recent years.
      We report four cases of angiosarcoma which occurred after treatment of breast
      cancer and review the literature. In two of these cases the angiosarcoma
      developed on the irradiated breast skin after partial mastectomy and radiation
      therapy, in the other two cases the angiosarcoma appeared on a chronically
      edematous arm after radical mastectomy and radiation therapy.

PMID- 10066961
TI  - Linear IgA bullous dermatosis in a patient with acute lymphocytic leukemia:
      possible involvement of granulocyte colony-stimulating factor.
AB  - We describe a case of linear IgA bullous dermatosis (LABD) in a patient with
      acute lymphocytic leukemia during treatment with granulocyte colony-stimulating
      factor (G-CSF). After a drug eruption due to imipenem cilastatin sodium had
      disappeared, bullous lesions appeared on the trunk. Results of histopathological
      studies and direct immunofluorescence studies of the lesion were consistent with
      LABD. Reinstitution of G-CSF after the resolution, however, did not reproduce the
      bullous eruptions. This suggests that in addition to G-CSF, the presence of
      precipitating factors that can synergistically enhance or accelerate the outbreak
      of the disease is required for the development of bullous lesions. Various
      cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma),
      endogenously produced from activated lymphocytes during the drug eruption might
      have provided a favorable milieu for the onset of G-CSF-induced LABD. We suggest
      that patients with LABD will need special attention with respect to the type of
      cytokines or combination of cytokines given as therapeutic modalities.

PMID- 10066962
TI  - Breaking the relentless course of Hallopeau's acrodermatitis by dapsone.
AB  - We report the case of a 74-year-old man who suffered for four years from
      recurrent generalized pustular eruptions associated with acrodermatitis continua
      of Hallopeau (ACH). Initial therapy using topical corticosteroids, tars and PUVA
      failed to improve the acral lesions. The disease was also unresponsive to
      systemic therapy using corticosteroids, methotrexate, etretinate, acitretine and
      cyclosporin A. Serious side-effects were experienced with these drugs. A marked
      improvement of the generalized pustules was observed under treatment combining
      etretinate and methotrexate, without having any effect on the acropustulosis.
      During hospitalization, a topical tar therapy cleared the pustular rash. Again no
      effect was observed on the acral lesions. Disulone (DDS) therapy, initiated at a
      dose of 200 mg/day, completely cleared ACH after 4 weeks. The disease relapsed
      when the dose was reduced to 100 mg/day. Increasing the DDS to 150 mg/day was
      rapidly followed by a new clearance of the acral lesions. After a 3-month
      treatment, the patient has remained lesion free and no DDS-related side-effects
      have occurred. In conclusion, sulfones may be considered as an alternative
      therapeutic option in drug-resistant ACH.

PMID- 10066963
TI  - Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?
AB  - We report on a patient with hyperimmunoglobulin E syndrome, who developed
      pruritic vesiculopapules from the age of six months and also had recurrent
      episodes of skin abscesses and oral thrush. Serum IgE was extremely elevated at
      59,514 IU/ml and specific IgE antibody to Staphylococcus aureus was positive.
      Histological examination from a vesiculopapule on the face revealed that
      eosinophil-rich infiltration involved hair follicles, similar to eosinophilic
      pustular folliculitis. We also examined cytokine profiles of circulating CD4+ T
      cells by intracellular cytokine staining and flow cytometry. The ratio of cells
      positive for interferon-gamma was significantly reduced compared with a control.
      Several reports have shown decreased interferon-gamma production by peripheral
      blood mononuclear cells of patients with hyperimmunoglobulin E syndrome. We think
      that this cytokine profile and the histological findings of our patient support
      the hypothesis that TH1/TH2 imbalance is involved in hyperimmunoglobulin E
      syndrome.

PMID- 10066964
TI  - Embolia cutis medicamentosa of the foot after sclerotherapy.
AB  - Typically, embolia cutis medicamentosa is reported after intramuscular injections
      of drugs. We describe a case of embolia cutis medicamentosa after sclerotherapy
      of intracutaneous veins of the foot with a polidocanol solution of 1%. Under
      therapy with intravenous alprostadil, pentoxifyllin, internal steroids and
      anticoagulation with heparin, the lesions healed completely without necrosis.

PMID- 10066965
TI  - A hyperkeratotic linear lesion in a girl with KID syndrome. A further example of
      early allelic loss?

PMID- 10066966
TI  - Contact dermatitis II. Clinical aspects and diagnosis.
AB  - Contact dermatitis (CD) is an altered state of skin reactivity induced by
      exposure to an external agent. "Eczema" and "dermatitis" are often used
      synonymously to denote a polymorphic pattern of inflammation of the skin
      characterized, at least in its acute phase, by erythema, vesiculation and
      pruritus. Substances that induce CD after single or multiple exposures may be
      irritant or allergic in nature. The clinical presentation may vary depending on
      the identity of the triggering agent and the reactivity of the subject, but in
      all cases the lesions are primarily confined to the site of contact. According to
      the mechanism of elicitation, the following types of contact reactions may be
      distinguished: (1) allergic contact dermatitis (ACD); (2) irritant contact
      dermatitis (ICD); (3) phototoxic and photoallergic contact dermatitis, and (4)
      immediate type contact reactions. The present review will focus on allergic
      contact dermatitis. ACD is the clinical presentation of contact sensitivity in
      humans. The pathophysiology of the contact sensitivity reaction has been reviewed
      in a preceding issue of this journal [1].

PMID- 10066967
TI  - Orthodontics: a case study in the tension between guild standards and capitalism.

PMID- 10066968
TI  - Patient-centered evaluation of orthodontic care: a longitudinal cohort study of
      children's and parents' attitudes.
AB  - As health services are adapted to meet consumers' needs, patient-centered
      evaluation of quality of care as well as informed consent to treatment decisions
      become increasingly important concepts in orthodontics. In an attempt to assess
      the orthodontic service in a region, this study focused on attitudes among
      children and their parents. The attitudes were recorded both before and after the
      period in which orthodontic treatment is usually carried out. Changes in
      children's and parents' attitudes were applied to measure outcome of care, and to
      evaluate the relevance of informed consent in decisions about treatment. Seventy
      nine family units were interviewed with the use of questionnaires when the child
      was 11 years of age and again at 16 years. Both orthodontically treated and
      untreated subjects were included. Responses to questions about satisfaction with
      dental appearance and desire for treatment were transformed to a score for
      orthodontic concern. A significant decrease in the concern score was observed
      over the 5-year period among the treated subjects, and the care system apparently
      identified and provided treatment to the majority of those children concerned at
      11 years. Intra-unit disagreement in concern was observed among 25% of the
      child/parent units at the 11-year stage, whereas at 16 years nearly all units
      agreed. Informed consent as a tool to ensure patients' autonomy when decisions
      about treatment are made did not appear to be negatively affected by conflicting
      attitudes between children and their parents.

PMID- 10066969
TI  - The Treatment Motivation Survey: defining patient motivation for treatment.
AB  - The Treatment Motivation Survey questionnaire is presented as a treatment
      planning tool designed to assist the patient and doctor in defining treatment
      expectations. With the Treatment Motivation Survey, motivation and expectations
      are mutually understood, and the treatment plan is successfully designed.
      Responses to the Treatment Motivation Survey questionnaire can also reveal
      patients whose expectations are unrealistic.

PMID- 10066970
TI  - Effect of changes in the breathing mode and body position on tongue pressure with
      respiratory-related oscillations.
AB  - The purpose of this study was to examine whether tongue pressure on the lingual
      surface of the mandibular incisors shows respiratory-related changes, with
      particular attention paid to its relationship to genioglossus electromyographic
      activity, and to determine the effect of changes in the mode of breathing and
      body position on tongue pressure. Tongue pressure was recorded with a miniature
      pressure sensor incorporated in a custom-made intraoral appliance in nine male
      subjects in different breathing modes and body positions. Electromyographic
      activity of the genioglossus muscle and respiratory-related movement were
      recorded simultaneously. Tongue pressure showed respiratory-related cyclic
      oscillations, with a maximum value during expiration and a minimum value during
      inspiration. In contrast, the activity of the genioglossus muscle showed a
      maximum amplitude during inspiration and a minimum amplitude during expiration.
      The maximum tongue pressure during oral breathing was significantly greater (P
      <.01) than during nasal breathing in both the upright and supine positions.
      Changes in body position significantly affected the maximum tongue pressure
      during oral breathing. The activity of the genioglossus muscle changed
      significantly with different breathing modes and body positions. Changes in the
      position of the hyoid bone produced by changes in the breathing mode and body
      position appear to have a critical role in determining tongue pressure.

PMID- 10066971
TI  - Mandibular length and midline asymmetry after experimentally induced
      temporomandibular joint disk displacement in rabbits.
AB  - The purpose of the present investigation was to test the hypothesis that
      permanent disk displacement in the temporomandibular joint (TMJ) is one causal
      factor in the development of mandibular midline asymmetry. Unilateral,
      nonreducing disk displacement was therefore created in growing rabbits. The right
      TMJ in seven experimental animals was surgically opened, and the disk was
      anteriorly displaced with the posterior disk attachment kept intact above the
      condyle. The right TMJ in seven sham animals was surgically opened and closed
      without any disk manipulation. Seven additional rabbits served as reference
      animals. For identification of mandibular growth, tantalum implants were inserted
      into the mandibular body, and lateral cephalograms were exposed at the beginning
      and at the end of the experimental period. After the animals had been sacrificed,
      the mandibles were dissected and measurements were performed on the mandibular
      specimens. Axial radiographs of the mandibles were then exposed and measurements
      of mandibular length and midline shift were performed in the radiographs. The
      mandible in the experimental animals was consistently shorter on the disk
      displacement side resulting in a midline shift to the ipsilateral side. No
      mandibular asymmetry was observed in the sham and reference groups. The
      hypothesis was verified; disk displacement in the TMJ with an onset during the
      growth period can cause mandibular length and midline asymmetry in growing
      rabbits.

PMID- 10066972
TI  - Management of impacted maxillary canines using mandibular anchorage.

PMID- 10066973
TI  - Relationship between anteroposterior maxillomandibular morphology and masticatory
      jaw movement patterns.
AB  - The causal relationships between oral function and craniomandibular morphology
      are poorly understood. The aim of this study was to determine whether
      quantifiable features of masticatory jaw movements and associated EMG activity
      correlated with variation in morphology as defined by the ANB angle. Thirty-six
      healthy subjects with no previous orthodontic treatment, asymptomatic masticatory
      muscles, and asymptomatic temporomandibular joints participated. While subjects
      chewed gum, jaw movement data and surface EMG data were digitized and then
      quantified into a 300 variable vector for each subject. ANB angle measurements
      were calculated from digitized tracings of lateral cephalographs. Step-wise
      linear regression and discriminant analyses were used to determine the
      relationship between the ANB angle and a subset of the variables defining jaw
      movement patterns and EMG patterns. A linear combination of seven jaw movements
      and EMG variables accounted for over 75% of the variation in the ANB angle
      (adjusted x R2 = 0.78, P <.001). A jackknifed cross-validation of the
      discriminant analysis, which was forced to use the same seven variables as the
      regression analysis, resulted in correct classification of 14 of 20 skeletal
      Class I, 7 of 9 skeletal Class II, and 7 of 7 skeletal Class III subjects. These
      results suggest that there is an association between anteroposterior skeletal
      morphology, as quantified by the ANB angle, and masticatory jaw movement
      patterns, as quantified in this study.

PMID- 10066974
TI  - Analysis of stress in the periodontium of the maxillary first molar with a three
      dimensional finite element model.
AB  - The aim of this study was to simulate the stress response in the periodontium of
      the maxillary first molar to different moment to force ratios, and to determine
      the moment to force ratio for translational movement of the tooth by means of the
      finite element method. The three-dimensional finite element model of the
      maxillary first molar consisted of 3097 nodes and 2521 isoparametric eight-node
      solid elements. The model was designed to dissect the periodontal ligament, root,
      and alveolar bone separately. The results demonstrate the sensitivity of the
      periodontium to load changes. The stress pattern in the periodontal ligament for
      a distalizing force without counterbalancing moments showed high concentration at
      the cervical level of the distobuccal root due to tipping and rotation of the
      tooth. After various counterrotation as well as countertipping moments were
      applied, an even distribution of low compression on the distal side of the
      periodontal ligament was obtained at a countertipping moment to force ratio of
      9:1 and a counterrotation moment to force ratio of 5:1. This lower and uniform
      stress in the periodontal ligament implies that a translational tooth movement
      may be achieved. Furthermore, high stress concentration was observed on the root
      surface at the furcation level in contrast with anterior teeth reported to
      display high concentration at the apex. This result may suggest that the root
      morphology of the maxillary first molar makes it less susceptible to apical root
      resorption relative to anterior teeth during tooth movement. The stress patterns
      in the periodontal ligament corresponded with the load types; those on the root
      appeared to be highly affected by bending and the high stiffness of the root.

PMID- 10066975
TI  - The wire material and cross-section effect on double delta closing loops
      regarding load and spring rate magnitude: an in vitro study.
AB  - The mechanical behavior of orthodontics closing loops, with three different wire
      materials (stainless steel, cobalt-chromium and titanium-molybdenum) and with
      different cross-sections and a double delta design, was studied in tension tests.
      The springs were stress-relieved, except the titanium-molybdenum wires. There
      were 72 sample springs, divided into 33 stainless steel, 26 cobalt-chromium and
      13 titanium-molybdenum, activated at 0.5 mm intervals, from neutral position to
      3.0 mm. It was hypothesized that loads, after spring activation, and spring rate,
      are dependent on cross-section, wire material, and activation. The analysis of
      variance and the Tukey-Kramer test were applied to verify the differences between
      all coupled averages of the loads. Regression analysis was also used to verify if
      closing loops behavior was in accordance with Hooke's law and to obtain the
      spring rate. The results show that the loads are dependent on activation, cross
      section, and wire material. Titanium-molybdenum 0.017 x 0.025 inch (Ormco)
      springs showed the smallest loads and the best spring rate. (beta = 84.9 g/mm)

PMID- 10066976
TI  - Retirement from orthodontics: financial and psychosocial preparation and
      adaptation.
AB  - Retired members of the Pacific Coast Society of Orthodontists (n = 231) were
      surveyed with respect to their financial and psychosocial preparation for, and
      adaptation to, retirement. Statistical and subjective evaluation of the survey
      results established that the respondents used a variety of strategies in
      divesting themselves of their practices and other aspects of professional life.
      The respondents reported a relatively high level of accumulated wealth and
      general satisfaction with retirement as a result of a sense of financial security
      as well as continued active participation in diverse recreational, social,
      avocational, business, family, and community activities. Early anticipation of
      and planning for all aspects of the retirement experience enhanced the likelihood
      of a satisfactory outcome.

PMID- 10066977
TI  - In vitro and in vivo fluoride release from orthodontic elastomeric ligature ties.
AB  - Clinically, demineralization of enamel around orthodontic attachments can occur
      after only 1 month. Fluoride incorporation into elastomeric ligature ties may
      provide additional protection against decalcification through fluoride release.
      This study compared the fluoride release of fluoride-impregnated and nonfluoride
      elastomeric ligature ties (Ortho Arch Company) both in vitro and in vivo. A total
      of 260 fluoride-impregnated and 260 nonfluoride elastomerics were evaluated in
      this study, 400 in vitro and 120 in vivo. For the in vivo part of the study, six
      patients had fluoride and nonfluoride elastomerics placed in cross-quadrant
      fashion in their mouths; these were removed and tested for residual fluoride
      release after 1 month. With the use of the potentiometric analytical method, the
      fluoride release of the elastomerics was determined in distilled water as the 24
      hour residual release, to compare the in vitro and in vivo fluoride leached into
      solution. The data was analyzed with the Wilcoxon matched-pairs signed ranks
      test. The distilled water control yielded an F- reading of 0.03 +/- 0.01
      microgram/F/mL. In the in vitro part of the study, an average of 0. 38
      microgram/F/mL/elastomeric was released over the 1 month period by the fluoride
      impregnated elastomerics; this decreased significantly (P <. 05) to a 24-hour
      residual value at 1 month of 0.02 microgram/F/mL/elastomeric ligature, which is
      in the same order of magnitude as the distilled water control solution. The
      nonfluoride ties produced a calculated 24 hour residual fluoride release of 0.
      003 microgram/F/mL/elastomeric after 1 month; this is much less than the
      distilled water control and would not be possible to measure accurately. After 1
      month in vivo, significantly greater (P >.05) amounts of 24-hour residual
      fluoride were apparent: F- elastomerics = 1.43 microgram/F/mL/elastomeric and
      nonfluoride elastomerics = 0.44 microgram/F/mL/elastomeric. Fluoride ties gained
      weight intra-orally. Residual, leachable fluoride was present in fluoride
      impregnated and nonfluoride elastomeric ligature ties after 1 month of intraoral
      use, due to imbibition. The clinical efficacy of fluoride-impregnated elastomeric
      ligature ties to prevent decalcification in the presence of plaque needs to be
      investigated.

PMID- 10066978
TI  - Identical twins treated differently.
AB  - This case study is intended to demonstrate the effects of two different
      orthodontic treatment methods on one set of identical twins.

PMID- 10066979
TI  - Stability of orthodontic treatment outcome: follow-up until 10 years
      postretention.
AB  - Dental casts of 1016 patients were evaluated for the long-term treatment outcome
      using the Peer Assessment Rating (PAR) index. The PAR index was measured at the
      pretreatment stage (n = 1016), directly posttreatment (n = 783), postretention (n
      = 942), 2 years postretention (n = 781), 5 years postretention (n = 821), and 10
      years postretention (n = 564). The mean absolute change as well as the percentage
      of change per year (relapse) related to the postretention stage was calculated.
      An analysis of variance was applied to compare the mean change in the PAR between
      cases with and without a fixed retainer at the postretention stage and up to 10
      years postretention. Drop-out analysis showed that more Class II Division 2 cases
      were lost to follow-up than cases of other Angle classes. The results indicate
      that 67% of the achieved orthodontic treatment result was maintained 10 years
      postretention. About half of the total relapse (as measured with the PAR index)
      takes place in the first 2 years after retention. All occlusal traits relapsed
      gradually over time but remained stable from 5 years postretention with the
      exception of the lower anterior contact point displacement, which showed a fast
      and continuous increase even exceeding the initial score. The presence of a fixed
      retainer had a positive effect on the PAR score. In cases with fixed retention,
      the relapse was 3.6 PAR points less at 5 years postretention and 4.6 points less
      at 10 years postretention. The results of this type of studies enable clinicians
      to inform their patients about treatment limitations in order to better meet
      their expectations.

PMID- 10066980
TI  - Arch width and form: a review.
AB  - A study of the literature reveals a variety of opinions on the potential for
      change in arch dimensions. The variations in sample sizes, treatment mechanics,
      and retention regimens may obscure relevant findings. These articles confirm some
      common findings, and a number of clinical cases are presented to illustrate these
      trends. It would seem that limited degrees of arch expansion can be produced
      regularly, but careful case selection is necessary. Arch expansion is most likely
      to be achieved in the growing patient with correction of crossbites, correction
      of a Class II malocclusion, and achievement of a good intercuspation without
      extractions.

PMID- 10066981
TI  - Localization of the unerupted maxillary canine: how to and when to.
AB  - Reasons for localizing impacted maxillary canines are outlined and methods of
      localization described. The favored method of radiographic localization is the
      parallax method (image/tube shift method). Tube shifts can be carried out in both
      the horizontal and the vertical planes. For a horizontal tube shift, two occlusal
      radiographs are recommended; for a vertical tube shift, a rotational panoramic
      radiograph and an occlusal radiograph are recommended. This latter combination is
      usually the combination of choice because the panoramic radiograph, which
      provides information about all the teeth in both arches, the two jaws, and the
      surrounding structures, is often taken as an initial radiograph and this
      combination only requires one additional exposure, the occlusal radiograph. To
      facilitate the interpretation of a vertical tube shift, the angle of the tube in
      the occlusal radiograph should be increased from the customary 60 degrees to 65
      degrees to 70 degrees to 75 degrees. Less accurate methods of radiographic
      localization are to use (1) image magnification of the impacted maxillary canines
      and (2) image superimposition of the impacted maxillary canines on the central or
      lateral incisor. Reasons why periapical radiographs are not recommended to be
      used for a horizontal tube shift or for a vertical tube shift in combination with
      a panoramic radiograph are explained. Indications to suspect palatal impaction
      may occur in the future if the patient is less than 10 years of age, and
      indications to suspect impaction may have occurred if the patient is more than 10
      years of age are discussed. Patient questionnaires are advocated to aid the
      clinician in anticipating palatal impaction, the most frequent impaction.

PMID- 10066982
TI  - Osteoclast activation and recruitment after application of orthodontic force.
AB  - In this study, whole body radioactive cobalt 60 (Co60) irradiation was used in an
      orthodontic tooth movement model to investigate osteoclast activation and
      recruitment in adult rats. Seventy-five rats were divided into three groups and
      were irradiated with Co60 ranging from 10 to 26 Gray. An orthodontic appliance
      was fitted to each rat 12 days after initiation of irradiation. Identical
      appliances were fitted on an additional 25 unirradiated rats. Groups of rats were
      sacrificed 1 week before and on the day of appliance placement as well as 1, 2,
      3, 4, or 5 weeks after appliance placement. Histologic sections from decalcified
      maxillary processes were prepared and osteoclasts were counted. Results showed
      that regardless of irradiation dosage, osteoclast number did not decrease during
      the first 3 weeks of orthodontic treatment; animals receiving lower (ie, 10 Gray)
      total irradiation actually showed a transient increase in the osteoclast number.
      In addition, regardless of dose in the irradiated rats, the total time
      osteoclasts were present in the periodontal membrane after orthodontic activation
      was reduced from 4 to 3 weeks. These findings lead us to hypothesize that
      osteoclasts involved in appliance-induced remodeling are initially from
      precursors in the periodontal membrane. During prolonged periods of orthodontic
      force application, replacement osteoclasts originate from bone marrow precursors.
      Although an orthodontic bone resorption cycle lasts 4 weeks, the life span of
      individual osteoclasts is limited to 9 to 10 days. The clinical significance of
      this finding remains to be elucidated.

PMID- 10066983
TI  - Charles henry tweed (1895-1970) 

PMID- 10066984
TI  - Reception room digital presentations.

PMID- 10066985
TI  - Small claims court step by step 

PMID- 10066986
TI  - Rescue treatment of acute parent vessel thrombosis with glycoprotein IIb/IIIa
      inhibitor during GDC coil embolization.

PMID- 10066987
TI  - [VIII Conference on Family and Community Medical Teaching and XVIII National
      Congress of Family and Community Medicine. Abstracts].

PMID- 10066988
TI  - Differential cognitive response to a mood challenge following successful
      cognitive therapy or pharmacotherapy for unipolar depression.
AB  - This study examined the nature of cognitive reactivity to mood changes in
      formerly depressed patients. Patients who recovered either through cognitive
      behavior therapy (CBT; N = 25) or through pharmacotherapy (PT; N = 29) completed
      self-reported ratings of dysfunctional attitudes before and after a negative mood
      induction procedure. In response to similar levels of induced sad mood, PT
      patients showed a significant increase in dysfunctional cognitions compared with
      patients in the CBT group. To evaluate the effects of such cognitive reactivity
      on the subsequent course of depression, follow-up analyses reassessed 30 patients
      several years after initial testing. Results indicated that patients' reactions
      to the mood induction procedure were predictive of depressive relapse. These
      findings argue for differential effects of treatment on cognitive reactivity to
      mood induction and for the link between such reactivity and risk for later
      depressive relapse.

PMID- 10066989
TI  - Drug-abusing patients and their intimate partners: dyadic adjustment,
      relationship stability, and substance use.
AB  - The dyadic adjustment and substance use of couples with a drug-abusing husband (n
      = 94), couples with a drug-abusing wife (n = 36), couples in which both partners
      abused drugs (n = 87), and non-substance-abusing conflicted couples (n = 70) were
      examined. For couples with 1 drug-abusing partner, a higher percentage of days
      abstinent during the year before treatment for drug abuse was associated with a
      higher level of relationship satisfaction. When both partners abused drugs, the
      relationship between percentage of days abstinent and relationship satisfaction
      became stronger and more negative as the time partners spent together using drugs
      increased. A higher percentage of days abstinent was associated with relationship
      stability for couples with 1 drug-abusing partner during and 1 year after
      treatment; for couples in which both partners abused drugs, a higher percentage
      of days abstinent was associated with relationship instability.

PMID- 10066990
TI  - Sex differences in genetic and environmental influences on DSM-III-R attention
      deficit/hyperactivity disorder.
AB  - Approximately 5% of children are affected by attention-deficit/hyperactivity
      disorder (ADHD), and more boys are affected than girls. This study examined the
      magnitude of genetic and environmental influences on ADHD and several questions
      regarding sex differences in its prevalence and liability. The participants were
      2,391 twin and sibling pairs from Australia, ages 3-18. ADHD symptoms in the
      general population were highly heritable (h2 = .85-.90), as were deviant ADHD
      scores in the selected population. The magnitude of familial influences was
      similar for boys and girls, although there were shared environmental influences
      on ADHD in girls but not boys and dominance genetic influences on ADHD in boys
      but not girls. Specific genetic and environmental influences were highly similar
      for boys and girls. Evidence supported the polygenic multiple threshold model
      rather than the constitutional variability model of sex differences in ADHD.

PMID- 10066991
TI  - Spatial frequency masking in positive- and negative-symptom schizophrenia.
AB  - The role of transient and sustained channels in masking was investigated in
      groups with positive and negative symptoms in schizophrenia and in a control
      group. The target stimulus was a 3.0 c/deg sinusoidal grating, which was masked
      at 11 stimulus-onset asynchronies between -40 to 360 ms by a 1.0 c/deg mask or an
      11.0 c/deg mask. The results showed that there was no difference between the
      control and positive-symptom groups in the perception of the 3 c/deg target
      stimulus, nor was there a difference when the target was masked by 1 or 11 c/deg
      masking stimuli. In comparison with the control and positive-symptom groups, the
      negative-symptom group showed a significantly higher threshold for the perception
      of the 3 c/deg target stimulus and more masking with a 1 c/deg mask, but not with
      an 11 c/deg mask. The results provide evidence for distinguishable differences in
      visual masking between groups with positive and negative symptoms in
      schizophrenia.

PMID- 10066992
TI  - The relationship between personality pathology and dysfunctional cognitions in
      previously depressed adults.
AB  - Multivariate and univariate regression models were used to examine the
      relationship between Axis II personality pathology and dysfunctional cognitions
      in a follow-up study of 40 formerly depressed inpatients. A dimensionalized
      measure of overall Axis II pathology was significantly and positively related to
      dysfunctional attitudes (Dysfunctional Attitudes Scale [DAS]) and maladaptive
      negative event attributions (Attributional Style Questionnaire-Negative Composite
      [ASQ-N]); the Axis II measure accounted for approximately 29% of the variance in
      DAS and 14% of the variance in ASQ-N, after controlling statistically for
      subsyndromal depressive symptoms (Beck Depression Inventory [BDI]). Axis II
      pathology was not significantly associated with positive event attributions, and
      no significant Axis II x BDI interaction effects were observed. A secondary
      canonical analysis of Axis II clusters was largely consistent with a hypothesized
      general personality pathology factor associated with dysfunctional cognitions,
      though a more specific association between Axis II Cluster C pathology and
      dysfunctional attitudes was also observed.

PMID- 10066993
TI  - Psychopathy across cultures: North America and Scotland compared.
AB  - Differences in the prevalence and presentation of psychopathic personality
      disorder between North America and Scotland were evaluated. R. D. Hare's (1991)
      Psychopathy Checklist--Revised ratings obtained from a sample of 2,067 North
      American male prisoners and forensic patients were compared with ratings obtained
      from 246 Scottish male prisoners. Item response theory methods were used to
      examine differences in the performance of items and to equate the scale across
      settings. The items had equal relevance to the description of psychopathic
      personality disorder in both settings; however, the Scottish prisoners had to
      have higher levels of the underlying latent trait before certain characteristics
      became apparent. The prevalence of the disorder appears to be lower in Scotland.
      Explanations for the observed differences in terms of enculturation,
      socialization, and migration are explored.

PMID- 10066994
TI  - Normal time course of auditory recognition in schizophrenia, despite impaired
      precision of the auditory sensory ("echoic") memory code.
AB  - Prior studies have demonstrated impaired precision of processing within the
      auditory sensory memory (ASM) system in schizophrenia. This study used auditory
      backward masking to evaluate the degree to which such deficits resulted from
      impaired overall precision versus premature decay of information within the short
      term auditory store. ASM performance was evaluated in 14 schizophrenic
      participants and 16 controls. Schizophrenic participants were severely impaired
      in their ability to match tones following delay. However, when no-mask
      performance was equated across participants, schizophrenic participants were no
      more susceptible to the effects of backward maskers than were controls. Thus,
      despite impaired precision of ASM performance, schizophrenic participants showed
      no deficits in the time course over which short-term representations could be
      used within the ASM system.

PMID- 10066995
TI  - Vulnerability to depression: reexamining state dependence and relative stability.
AB  - Treatment-related decreases in Dysfunctional Attitudes Scale (DAS; Weissman &
      Beck, 1978) scores have been interpreted as evidence that dysfunctional attitudes
      are state-dependent concomitants of depression. Data from the National Institute
      of Mental Health Treatment of Depression Collaborative Research Program were used
      to reexamine the stability of dysfunctional attitudes. Mean scores for
      Perfectionism, Need for Approval, and total DAS decreased after 16 weeks of
      treatment. However, test-retest correlations showed that the DAS variables
      displayed considerable relative stability. Structural equation models
      demonstrated that dysfunctional attitudes after treatment were significantly
      predicted by initial level of dysfunctional attitudes as well as by posttreatment
      depression. The relative stability of dysfunctional attitudes was even higher
      during the 18-month follow-up period. The results were consistent with Beck's
      (1967) and Blatt's (1974) theories of vulnerability.

PMID- 10066996
TI  - Effects of methylphenidate on complex cognitive processing in attention-deficit
      hyperactivity disorder.
AB  - Three experiments were conducted to explore the effects of methylphenidate (MPH),
      attention-deficit hyperactivity disorder (ADHD) diagnosis, and age on performance
      on a complex visual-memory search task. Results showed that the effects of MPH
      varied with information load. On low-processing loads, all doses of MPH helped
      children with ADHD to improve accuracy with no cost to reaction time (RT),
      whereas on high loads, higher MPH doses improved error rates while slowing RT.
      Without medication, children with ADHD showed high error rates and slow RTs
      across both low and high loads, as did younger, normal control children. Because
      MPH slowed performance on only the most difficult, high-load conditions, it is
      argued that the drug improves self-regulatory ability, enabling children with
      ADHD to adapt differentially to high and low loads.

PMID- 10066997
TI  - A longitudinal study of children of alcoholics: predicting young adult substance
      use disorders, anxiety, and depression.
AB  - This study tested the specificity of parent alcoholism effects on young adult
      alcohol and drug abuse/dependence, anxiety, and depression, and tested whether
      adolescent symptomatology and substance use mediated parent alcoholism effects.
      Participants were from a longitudinal study in which a target child was assessed
      in adolescence and young adulthood with structured interview measures (N = 454
      families at Time 1). Results showed unique effects of parent alcoholism on young
      adult substance abuse/dependence diagnoses over and above the effects of other
      parental psychopathology. There was some evidence of parent alcoholism effects on
      young adult depression and of maternal alcoholism effects on young adult anxiety,
      although these were not found consistently across subsamples. Mediational models
      suggested that parent alcoholism effects could be partially (but not totally)
      explained by adolescent externalizing symptoms.

PMID- 10066998
TI  - Context-processing deficits in schizophrenia: converging evidence from three
      theoretically motivated cognitive tasks.
AB  - To test the hypothesis that the ability to actively represent and maintain
      context information in a central function of working memory and that a
      disturbance in this function contributes to cognitive deficits in schizophrenia,
      the authors modified 3 tasks--the AX version of the Continuous Performance Test,
      Stroop, and a lexical disambiguation task--and administered them to patients with
      schizophrenia as well as to depressed and healthy controls. The results suggest
      an accentuation of deficits in patients with schizophrenia in context-sensitive
      conditions and cross-task correlations of performance in these conditions.
      However, the results do not definitively eliminate the possibility of a
      generalized deficit. The significance of these findings is discussed with regard
      to the specificity of deficits in schizophrenia and the hypothesis concerning the
      neural and cognitive mechanisms that underlie these deficits.

PMID- 10066999
TI  - Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War
      veterans with posttraumatic stress disorder.
AB  - Aversive conditioning to explicit and contextual cues was examined in Gulf War
      veterans with and without posttraumatic stress disorder (PTSD) by use of the
      startle reflex methodology. Veterans participated in a differential aversive
      conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each
      session comprised two startle habituation periods, a preconditioning phase, a
      conditioning phase, and a postconditioning extinction test. In contrast to the
      non-PTSD group, the PTSD group showed a lack of differential startle response in
      the presence of a conditioned stimulus with or without an unconditioned stimulus
      in Session 1 and an increase in the baseline startle response during Session 2.
      The PTSD group also exhibited normal differential conditioning following
      reconditioning in Session 2. These data suggest that individuals with PTSD tend
      to generalize fear across stimuli and are sensitized by stress.

PMID- 10067000
TI  - Fear-relevant images as conditioned stimuli for somatic complaints, respiratory
      behavior, and reduced end-tidal pCO2.
AB  - Two fear-relevant imagery scripts were used as conditioned stimuli (CSs) in a
      differential learning paradigm with 5.5% CO2-enriched air as unconditioned
      stimulus (US). In another condition, 2 neutral scripts were used as CSs (N = 56).
      Within each condition, one script was imagined while breathing the CO2-enriched
      air (CS+/US trial), the other while breathing room air (CS- trial). Three CS+ and
      3 CS- trials were run in an acquisition phase, followed by 2 CS+ and 2 CS- test
      trials (imagining the scripts while breathing air). Respiratory behavior, end
      tidal CO2, and heart rate were measured throughout the experiment; subjective
      symptoms were measured after each trial. The type of imagery had strong effects
      on symptoms and physiological responses. A selective conditioning effect was also
      observed: CS+ imagery produced more symptoms and altered respiratory behavior
      compared with CS- imagery, but only in the fear-relevant script condition. The
      findings are discussed as to their relevance for panic and agoraphobic anxiety.

PMID- 10067001
TI  - Explicit memory in anxiety disorders.
AB  - Two experiments were conducted to study selective memory bias favoring anxiety
      relevant materials in patients with anxiety disorders. In the 1st experiment, 32
      patients with generalized anxiety disorder (GAD), 30 with social phobia (speaking
      anxiety), and 31 control participants incidentally learned GAD-relevant words,
      speech anxiety-relevant words, strongly pleasant words, and words with a neutral
      valence. Participants did not show any explicit memory bias for threatening
      materials. Thirty patients suffering from panic disorder (PD) with agoraphobia
      and 30 controls took part in the 2nd experiment. The design was similar to the
      1st experiment. This time a highly specific selective memory bias for threatening
      words was found. Words describing symptoms of anxiety were better recalled by PD
      patients. Results are consistent with previous findings but are inexplicable by
      existing theories.

PMID- 10067002
TI  - Posttraumatic stress disorder in a national sample of female and male Vietnam
      veterans: risk factors, war-zone stressors, and resilience-recovery variables.
AB  - Relationships among pretrauma risk factors (e.g., family instability, childhood
      antisocial behavior), war-zone stressors (e.g., combat, perceived threat),
      posttrauma resilience-recovery variables (e.g., hardiness, social support), and
      posttraumatic stress disorder (PTSD) symptom severity were examined. Data from a
      national sample of 432 female and 1,200 male veterans were analyzed using
      structural equation modeling. For both genders, direct links to PTSD from
      pretrauma, war-zone, and posttrauma variable categories were found; several
      direct associations between pretrauma and posttrauma variables were documented.
      Although war-zone stressors appeared preeminent for PTSD in men, posttrauma
      resilience-recovery variables were more salient for women. Researchers,
      policymakers, and clinicians are urged to take a broad view on trauma and its
      sequelae, especially regarding possible multiple exposures over time and the
      depletion and availability of important resources.

PMID- 10067003
TI  - Selective attention in obsessive-compulsive disorder.
AB  - Recent information-processing studies have suggested that a selective attention
      deficit may be involved in the symptomatology of obsessive-compulsive disorder
      (OCD). In this study, individuals diagnosed with OCD were distinguished from
      those with panic disorder and from control participants by their relatively
      poorer performance on a series of psychometric tasks of selective attention.
      These results are interpreted as supporting the hypothesis of a diminished
      ability of people with OCD to selectively ignore competing external (sensory) and
      internal (cognitive) stimuli, especially intrusive thoughts.

PMID- 10067004
TI  - Neuropsychological functioning among the nonpsychotic relatives of schizophrenic
      patients: a 4-year follow-up study.
AB  - In a prior study of 54 relatives of patients with schizophrenia and 72 control
      participants, 3 neuropsychological functions met the criteria for risk indicators
      of the schizophrenia genotype: executive functioning, memory, and auditory
      attention. In an assessment of the stability of these findings, the sample was
      reexamined 4 years after the initial assessment. Three test scores were found to
      differ between groups (Immediate Verbal Memory, Delayed Verbal Memory, and
      Dichotic Listening Digits Detected) or to show a significant Group x Gender
      interaction (immediate and delayed verbal and visual memories). None of the test
      scores showed Group x Time interactions, suggesting that the discriminating power
      of the tests was stable over time. Evidence for deficits in working memory and
      rule learning on the object alternation test was also found. These results
      support the idea that neuropsychological dysfunction among relatives of patients
      with schizophrenia is a stable trait caused by the familial predisposition to
      schizophrenia.

PMID- 10067005
TI  - Deeper into the schizotypy taxon: on the robust nature of maximum covariance
      analysis.
AB  - Prior research has suggested that the latent structure of the schizotypy
      construct (P. E. Meehl, 1990) may be qualitative in nature and have a low base
      rate (L. Korfine & M. F. Lenzenweger, 1995; M. F. Lenzenweger & L. Korfine,
      1992). These studies relied on the application of maximum covariance analysis
      (MAXCOV) to 8 true-false format items from a schizotypy measure. The current
      study sought to examine the robustness of those prior findings through MAXCOV
      analysis of fully quantitative measures of schizotypy. Measures of perceptual
      aberration, magical ideation, and referential thinking were analyzed using MAXCOV
      in a sample of 429 persons. The results of these analyses strongly support a
      latent taxonic structure for schizotypy and a low base rate for the schizotypy
      taxon. Furthermore, the members of the putative taxon reveal an increased level
      of deviance on a psychometric measure known to be associated with schizophrenia
      liability. The possibility that the dichotomous item format of those items
      analyzed previously with MAXCOV lead to spurious pseudotaxonicity is greatly
      diminished in light of these results.

PMID- 10067006
TI  - Genital fistulae. A continuing tragedy.

PMID- 10067007
TI  - Glucose transporter 4 (GLUT4) mRNA abundance in the adipose tissue and skeletal
      muscle tissue of ovariectomized rats treated with 17 beta-estradiol or
      progesterone.
AB  - OBJECTIVE: To investigate the effects of 17 beta-estradiol and progesterone on
      the expression of glucose transporter 4 (GLUT4) in the adipose tissue and
      skeletal-muscle tissue of ovariectomized rats. METHODS: Female Sprague-Dawley
      rats (n = 63) received a daily subcutaneous injection of 10 micrograms, 50
      micrograms, or 250 micrograms of 17 beta-estradiol (Group E) or of 1 mg, 5 mg or
      25 mg of progesterone (Group P) for 3 days, 7 days, or 10 days (n = 3, at each
      dose). The expression of GLUT4 mRNA was assessed by performing ribonuclease
      protection assays. RESULTS: The levels of GLUT4 mRNA in adipose tissue was
      significantly reduced by treatment with estradiol, 50 micrograms or 250
      micrograms, relative to findings in control rats (p < 0.01). No such reductions
      were seen regarding the progesterone treatment. The level of GLUT4 mRNA in
      skeletal-muscle tissue did not change, regardless of treatment. CONCLUSION: In
      ovariectomized rats, higher than physiologic dosages of 17 beta-estradiol can
      suppress the expression of GLUT4 mRNA in adipose tissue.

PMID- 10067008
TI  - Immunohistochemical and ultrastructural study of Langerhans's cells in squamous
      cell carcinoma of the cervix.
AB  - OBJECTIVE: To study Langerhans's cells (LCs) in cervical squamous cell carcinoma.
      STUDY DESIGN: The study was carried out in the Shatby University Hospital,
      Alexandria, Egypt. Thirty cases with squamous cell carcinoma, 10 cases with
      cervical intra-epithelial neoplasia (CIN) and 10 cases with normal exocervix were
      recruited. Sections from the exocervix were stained with gold chloride,
      immunostaining with S-100 protein antiserum, adenosine triphosphatase ATPase and
      electron microscopy. Statistical evaluation was done using the t-test. RESULTS:
      Gold chloride staining revealed significantly increased number of LCs in all
      cases of CIN compared to normal controls and with increasing grade of CIN (p <
      0.001). No relationship between LCs number and the grade of carcinoma. Least
      branched LCs were predominant in the normal tissue while in neoplasia, these
      cells were of the most branched type, indicating a hyperactivity. S-100 protein
      positive LCs were almost absent in normal controls while their number were almost
      lower than the corresponding cases of CIN and invasive carcinoma after gold
      chloride or ATPase stainings. Signs of hyperactivity were evident in LCs of
      neoplastic cases after electron microscopy. CONCLUSIONS: Proliferation and
      increased number of LCs in CIN is an immune response, while such reaction is
      suppressed by invasive carcinoma.

PMID- 10067009
TI  - Interleukin-6 (IL-6) does not change the expression of Bcl-2 protein in the
      prevention of cisplatin-induced apoptosis in ovarian cancer cell lines.
AB  - OBJECTIVE: To study whether interleukin-6 (IL-6) changes the expression of the
      anti-apoptic Bcl-2 protein in the prevention of cis-diaminedichloroplatinum (II)
      (CDDP)-induced apoptosis of human ovarian cancer cells. METHODS: Comparative
      studies were performed on 3 ovarian cancer cell lines after 48 hours of exposure
      to 0.5-50 ng/ml IL-6, 2 micrograms/ml anti-IL-6 monoclonal antibody (anti-IL-6
      mAb), 10 microM CDDP, 10 microM CDDP + 0.5-50 ng/ml IL-6, and 10 microM CDDP + 2
      micrograms/ml anti-IL-6 mAb. Apoptosis was measured morphologically and by a DNA
      fragmentation assay. Bcl-2 protein levels were measured by an ELISA. RESULTS: An
      increase in apoptosis was observed for each cell line after 48 hours of exposure
      to 10 microM CDDP. Although high doses of IL-6 decreased the percentage of
      apoptotic cells, this cytokine did not change the expression of the Bcl-2
      protein. CONCLUSION: CDDP-induced apoptosis was negatively controlled by IL-6.
      However, the anti-apoptic Bcl-2 protein level was not changed by IL-6 in the
      process of apoptosis in the ovarian cancer cell lines.

PMID- 10067010
TI  - A case report: rare case of primary transitional cell carcinoma of the fallopian
      tube.
AB  - Carcinomas other than adenocarcinomas are extremely rare in the fallopian tube. A
      42-year-old woman with watery, intermittent vaginal discharge was found to have a
      left adnexal tumor. This case was diagnosed as primary carcinoma of the fallopian
      tube, FIGO Stage Ia. She underwent a total abdominal hysterectomy, a bilateral
      salpingo-oophorectomy, a pelvic and periaortic lymphoadenectomy, and an
      omentectomy, followed by cisplatin-based chemotherapy. Four years after the
      initial diagnosis of the disease, she remains in a disease-free state.
      Histologically, the tumor revealed a primary transitional cell carcinoma of the
      left fallopian tube. The findings on an immunohistochemical test for an
      epithelial membrane antigen, the CA125 antigen, were positive, whereas findings
      on a test for CEA were negative. We report a case of a malignant neoplasm of the
      fallopian tube with histological features of transitional cell carcinoma that
      arose from the tubal epithelium.

PMID- 10067011
TI  - Elective induction of labor at 39 weeks of gestation: a prospective randomized
      trial.
AB  - OBJECTIVE: To clarify the safety of elective induction of labor at 39 weeks of
      gestation. STUDY DESIGN: Prospective randomized study. SUBJECTS AND METHODS:
      Uncomplicated nulliparas (N = 194) were randomly assigned at 36 weeks of
      gestation. Labor was electively induced in 63 women at 39 weeks of gestation in
      the active management group (I group, N = 98). Spontaneous labor onset was
      expected with semi-weekly nonstress test (NST) and amniotic fluid index (AFI) by
      42 weeks of gestation in the expectant group (E group, N = 96). Perinatal events
      were compared between the 2 groups. RESULTS: A significantly higher incidence of
      meconium-stained amnios (19.4% vs 3.2%) and fetal resuscitation (16.7% vs 4.8%)
      was found in the E group than in the I group. Also, although a significantly
      higher incidence of epidural analgesia was noted in the I group (89%) than in the
      E group (54%) (labor onset > or = 39 weeks, N = 72), the duration of the 1st
      stage was shorter in I group and the duration of the 2nd stage was not
      significantly different. No other significant difference was noted between the 2
      groups in terms of the rate of C-section, blood loss, incidence of pathological
      FHR, birth weight, Apgar score, umbilical arterial pH, or admission to NICU.
      CONCLUSION: Active management of labor at 39 weeks could be made as safely as
      expectant management with modified biophysical profile monitoring.

PMID- 10067012
TI  - The association between maternal smoking and fetal hydranencephaly.
AB  - OBJECTIVE: To evaluate the relationship between maternal smoking and fetal
      congenital central nervous system malformations. METHODS: Retrospective review of
      all cases of fetal congenital malformations of the central nervous system (CNS)
      identified at or shortly after birth over a 10-year period (1986-1995) in a
      university teaching obstetric department. RESULTS: The total number of CNS
      abnormalities identified was 79, constituting 0.13% of all deliveries over the
      period (n = 59,392) and 4.7% of all congenital malformations (n = 1,678). The
      incidence of smoking mothers was 1.64% over the study period. Four babies had
      hydranencephaly, 3 of these mothers being smoking teenagers. The odds ratio of
      having a hydranencephalic fetus in smoking mothers compared to non-smokers was 56
      (95% CI 7.41-427) in the group with CNS abnormalities, 136 (95% CI 14.5-1280) in
      the group including all congenital malformations, and 179 (95% CI 18.6-1719) in
      the group including all deliveries. CONCLUSION: Maternal smoking did not appear
      to increase the incidence of fetal congenital CNS abnormalities overall, but
      might be associated with particular vascular patterns of damage to the developing
      brain that could predispose to a hydranencephalic malformation.

PMID- 10067013
TI  - Psychological and obstetrical responses of mothers following antenatal fetal sex
      identification.
AB  - This work was designed to study the impact of prenatal knowledge of fetal sex
      both on the psychological and obstetrical aspects of the expectant mothers during
      pregnancy and labour. One hundred pregnant women attending the outpatient
      antenatal clinic of Assiut University Hospital were recruited. All were in the
      third trimester, parous, with normal pregnancy and having no past or present
      psychiatric disorders. The desired sex of the expected child was registered.
      Symptom checklist 90 (SCL-90) was applied before, and 2 weeks after sonographic
      fetal sex determination. Women who desired male sex scored significantly higher
      depressive symptoms than those who desired female sex. Women who were proven
      sonographically to have the undesired fetal sex showed significantly higher
      scores of depression, somatization, anxiety, hostility and phobia scales of SCL
      90 than women whose desired fetal sex was confirmed. The second part of the study
      to evaluate the effect of knowing the fetal sex on the progress of labour was
      designed as a case control study including 57 women previously informed about
      their fetal sex and 40 women ignorant of their fetal sex as controls. Women
      delivering a baby with undesired sex showed more obstetric difficulties. In the
      first stage of labour, they had significant reduction in frequency of uterine
      contractions and rate of cervical dilatation. They also needed much more
      sedation, analgesia and oxytocin augmentation.

PMID- 10067014
TI  - Obstetrical management following incontinence surgery.
AB  - OBJECTIVE: To analyze in a retrospective fashion our experiences with obstetrical
      management following previous incontinence surgery. METHODS: Between 1990 and
      1997 4 women presented to our institution in the third trimester of pregnancy
      with a history of colposuspension performed 3 months to 4 years before onset of
      pregnancy for second degree stress incontinence. Three of 4 patients experienced
      recurrent incontinence during the third trimester. RESULTS: A cesarean section
      was performed before the onset of labor in all 4 patients. Postpartal pelvic
      floor exercises were prescribed and a follow-up ensued after 6 and 11 months in
      the form of a questionnaire. While incontinence persisted in 2 patients for 6
      months, all 4 patients demonstrated complete continence after one year.
      CONCLUSIONS: We consider an elective cesarean section to be the optimal mode of
      delivery in women with a history of incontinence surgery.

PMID- 10067015
TI  - Rational type of laparoscopic hysterectomy and safety in anesthetic profiles.
AB  - OBJECTIVE: To evaluate what type of surgery would be more reasonable among 3
      types of laparoscopic hysterectomy and to evaluate the safety of cardio-pulmonary
      changes on these patients during these operations. METHOD: A retrospective study
      was carried out in 215 women who underwent laparoscopic hysterectomy including
      laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic hysterectomy
      (LH), total laparoscopic hysterectomy (TLH). Blood gas analysis, end-tidal CO2
      levels and vital signs were checked and compared with control and preceding
      values. RESULTS: The average duration of operation was 102.5 min, 83.8 min and
      118.3 min for LAVH (n = 97), LH (n = 75) and TLH (n = 43), respectively (p <
      0.05). The average amount of bleeding was 297.5 ml, 152.3 ml and 149.2 ml for
      each type of hysterectomy, respectively. Hemoglobin decreased by an average of
      1.6 g/100 ml, 0.9 g/100 ml and 0.8 g/100 ml, respectively. There was a lesser
      amount of bleeding for LH and TLH than for LAVH (p < 0.05). Profiles of blood gas
      analysis and expiratory CO2 varied significantly according to the operative
      stages under controlled anesthesia (p < 0.05), but were within the normal range.
      CONCLUSION: These results demonstrate that laparoscopic procedures advancing
      below the uterine vasculature can be considered effective for hysterectomies and
      that proper anesthesia can safely control the cardio-pulmonary changes during
      laparoscopic hysterectomy.

PMID- 10067016
TI  - Pregnancy-associated osteoporosis with elevated levels of circulating parathyroid
      hormone-related protein: a report of two cases.
AB  - Two lactating women who had complained of back pain developed spontaneous
      vertebral fractures with low bone mineral density (BMD) several months
      postpartum. The back pain and biochemical abnormalities presented as
      hypercalcemia and elevated plasma levels of the parathyroid hormone-related
      protein (PTH-rP) that returned to normal indices with increasing BMD after
      weaning. The increased circulating PTH-rP might contribute to the pregnancy
      associated osteoporosis in women who probably are already osteopenic.

PMID- 10067017
TI  - Absence of hypertension: a bad prognostic sign in placental abruption.

PMID- 10067018
TI  - Everybody on the banding bandwagon?

PMID- 10067019
TI  - Appendicitis: a continuing challenge.
AB  - Acute appendicitis is a common surgical emergency in urban setting, of a
      developing country. The computerised hospital patient database at Aga Khan
      University Hospital, Karachi, was utilised to obtain records of all adults with a
      histologically proven diagnosis of acute appendicitis. A review of patients
      treated over a 18 month period was undertaken. One hundred and three
      appendicectomies were performed for acute appendicitis during this period. The
      diagnosis was clinical in all cases. Investigations like leucocyte count and
      lower abdominal ultrasound scan were used to improve diagnostic accuracy without
      a clear advantage. A number of routine investigations like, haemoglobin
      estimation and urea, creatinine, electrolyte measurements, did not provide
      additional information. The duration of antibiotic treatment in acute simple
      appendicitis was empiric and could be reduced to a single preoperative dose.
      Peritoneal fluid culture studies had a poor yield (26%) and results were not
      found to effect management in acute simple appendicitis. The routine use of
      Ampicillin in all cases of bacterial peritonitis needs re-evaluation, as a high
      incidence (73%) of resistance was seen. Studies to define the role and duration
      of treatment, with a single antibiotic, in acute simple appendicitis should be
      undertaken. Acute appendicitis is probably the most frequently considered
      surgical differential diagnosis at any hospital dealing with acute surgical
      conditions. The established treatment continues to be surgical removal of the
      inflamed organ. The diagnosis and decision to operate both are accepted to be
      based on clinical judgement, though a number of investigative manoeuvres have
      been described to reduce the negative appendicectomy rate. Other areas of debate
      are the number and length of antibiotic treatment and use of bacterial culture
      studies in cases of simple acute appendicitis. To analyse present practice and
      identify areas for study and change, a retrospective study was undertaken at Aga
      Khan University Hospital (AKUH), Karachi.

PMID- 10067020
TI  - Band ligation vs endoscopic sclerotherapy in esophageal varices: a prospective
      randomized comparison.
AB  - OBJECTIVE: A prospective randomized trial was conducted to compare efficacy,
      safety and complications of band ligation (BL) with sclerotherapy (Scl). METHODS:
      Patients with esophageal variceal bleeding were randomized into two study groups.
      BL (group A) was done in 28 patients whereas 30 patients (group B) had Scl. After
      initial treatment, follow-up sessions were repeated by the same method every two
      weeks till obliteration or reduction to grade 1. Subsequent sessions of endoscopy
      were done every three months, same procedure was repeated for recurrence of
      varices and for any episode of rebleeding. RESULTS: Initial control of bleeding
      by Scl was achieved in 22 of 28 patients (78%) and in 23 of 24 patients (96%)
      with BL. Eradication of varices was significantly better achieved in BL group,
      with less treatment sessions required in Group A as compared with group B 2 +/-
      1.2 vs 5 +/- 2.5, P < 0.001). Major complications (3% vs 16%, P < 0.05) as well
      as mortality (11% vs 21%, P > 0.05) was higher in group B. CONCLUSION: Band
      ligation was more effective mode of treatment and was associated with lesser
      early mortality and complications as compared with sclerotherapy.

PMID- 10067021
TI  - Hiatal hernia in achalasia.
AB  - Barium esophagograms of 89 patients out of 110 with manometrically proven
      achalasia were reviewed. Only four (4.4%) patients showed association of hiatal
      hernia, indicative of its rare occurrence. Presence of hiatal hernia, is said to
      have less likelihood of associated achalasia but this association does exist as
      per our report and that of others.

PMID- 10067022
TI  - Hepatocellular carcinoma: analysis of 76 cases.
AB  - Hepatocellular carcinoma is one of the most common malignancies world wide. We
      present data on 76 patients admitted to the Shaikh Zayed Hospital. Mean age was
      52.2 +/- 11.3 years. Eighty six percent were males and 14% females. Eighty-six
      percent patients had underlying cirrhosis documented on ultrasound examination.
      Seventy-five percent were positive for anti HCV, 10% for HBsAg positive, 10% for
      both HBsAg and anti HCV and 5% cases had negative viral serology. Main clinical
      features were abdominal pain, weight loss, jaundice, hepatomegaly and ascites.
      Forty-three percent patients were Child-Pugh class A, 30% class B and 13% class C
      and 14% were non cirrhotic. Mean alfa fetoprotein levels were 142 +/- 155 ng/ml
      (range 2.7 to 1470). Diagnosis of hepatocellular carcinoma was established in 60
      patients by fine needle aspiration biopsy under ultrasound guidance. Two patients
      died after biopsy due to uncontrollable bleeding. Fifty-four percent patients had
      a solitary lesion and 46% had multifocal or diffuse lesions. The average size of
      lesion was 7.8 x 8.1 cm. Twenty-two patients received intralesional alcohol
      injection. Fifty-four percent of these with a tumor size greater than 8 cm died
      during follow up. The major cause of death was liver failure in 8 patients and
      fatal bleeding occurred in 4 patients. Hepatocellular carcinoma has a high
      prevalence in middle aged males with a strong association with anti HCV positive
      cirrhosis. Patients with a tumour size greater than 8 cm have a poor response to
      intralesional alcohol injection.

PMID- 10067023
TI  - Prevalence of Helicobacter pylori antibodies in endoscopy personnel and non
      medical volunteers of Karachi.
AB  - Prevalence of Helicobacter pylori (Hp) is high in developing countries. As
      endoscopy personnel are at greater risk of exposure to gastric secretions, they
      are apparently at higher risk of acquiring this infection. The aim of this study
      was to determine prevalence of Hp antibodies in endoscopy staff and compare it
      with non-medical volunteers and assess any additional risk of occupational
      exposure to Hp in the former group. Thirty-three subjects working in endoscopy
      suites of different hospitals of Karachi and 33 non-medical volunteers were
      investigated for the prevalence of Hp antibodies by using a commercially
      available rapid qualitative test (FlexPack HP; Abbott). The two groups were
      comparable in mean age, sex and social class. Twenty-six of 33 (79%) of the
      endoscopy personnel and 19/33 (58%) of the non-medical volunteers were positive
      for Hp serology (p = 0.06 R.R 1.37). Among the endoscopy personnel 13/14 (93%) of
      endoscopy assistants were positive and this subgroup had a significantly higher
      prevalence of Hp antibodies as compared to the control group (p = 0.019). No
      correlation could be found between the positive serology and symptoms of
      dyspepsia.

PMID- 10067024
TI  - CLO antibody assay--can it be an alternate to endoscopy and biopsy?

PMID- 10067025
TI  - Hydatidosis: experience with hepatic and pulmonary hydatid disease.
AB  - From 1989-1992, 35 cases comprising of 20 hepatic and 15 pulmonary hydatid cysts
      were seen. Four patients with pulmonary hydatid disease had previous or
      concomitant hepatic hydatidosis compared to no concomitant pulmonary hydatid
      disease in the hepatic group. Hepatic hydatid disease had a greater tendency to
      be right sides, infected and calcified. Anaphylactic reactions occurred in 3 of
      20 patients with hepatic hydatid disease against none in 15 patients with
      pulmonary disease. Management consisted of evacuation, drainage and obliteration
      of the residual cavity by capittonage in the lung and omentoplasty in the liver.
      Two patients, one hepatic and one with pulmonary hydatid disease developed
      infection of the residual cavity. Bronchocystic fistula occurred in 4 pulmonary
      and cystobiliary fistula in 2 hepatic hydatid disease patients. One patient with
      severe pleuropulmonary hydatidosis required a thoracoplasty. No recurrences have
      been noted in either group over a mean follow-up of 11 months (range 3 weeks- 3
      years).

PMID- 10067026
TI  - Management of gall stones: the current perspective.

PMID- 10067027
TI  - Insulin lispro--a review.

PMID- 10067028
TI  - Introducing the Internet to medical practitioners.
AB  - The benefits of using the Internet to medical practitioners are growing rapidly,
      as the Internet becomes easier to use and ever more biomedical resources become
      available on net. The Internet is the largest computer network in the world that
      connects millions of computers in a web and makes almost immediate communication
      possible, irrespective of the location of its users. There are various ways to be
      connected with Internet and once connected, it is easy to take advantage from
      this space of unlimited potentials. Several Internet applications are available
      today that will bring more information to the doctors' desk. Although, it is
      difficult to predict the future of medicine on the Internet, but the net has
      opened up many new possibilities for medical professionals, which were not
      available through previous technologies. It is now up to them to realize the
      Internet's full potential. A non-technical overview of Internet, a glimpse of
      electronically available information and the methods available to access,
      manipulate and disseminate biomedical data from the Internet are discussed. These
      methods are useful for beginners as well as beneficial for experienced
      physicians.

PMID- 10067029
TI  - Well differentiated hepatocellular carcinoma metastasizing to jaw and oral cavity
      within six months of primary diagnosis.

PMID- 10067030
TI  - Mannitol osmotherapy in haemodynamically stable head injury patients--risk of
      sudden hypotension--a case report.

PMID- 10067031
TI  - Congenital bilateral diaphragmatic eventration--a rare anomaly with complicated
      perioperative care.

PMID- 10067032
TI  - Blindness in postpartum period: spinal analgesia or pre-eclampsia caused it?

PMID- 10067033
TI  - Locally produced drugs need quality control.

PMID- 10067034
TI  - Research and the changing truths.

PMID- 10067035
TI  - End stage renal failure--dilemmas and hope!

PMID- 10067036
TI  - Evaluation of the effect of haemodialysis on cardiac dysfunction in patients of
      chronic renal failure.
AB  - Thirty-eight patients with end stage renal disease who were on haemodialysis and
      had recurrent congestive cardiac failure were analysed. Echocardiographic
      findings were evaluated at start of haemodialysis and after 6 dialysis sessions.
      Seventeen cases (48%) had diastolic dysfunction, 11 (29%) systolic dysfunction 8
      (18%) had normal echocardiogram and 2 (5%) had dilated left ventricle with normal
      ejection fraction. In the systolic dysfunction group the end diastolic diameter
      decreased after 6 dialysis sessions. In the diastolic dysfunction group the end
      diastolic diameter and ejection fraction decreased minimally. In the systolic
      dysfunction group 8 patients (42%) expired within 18 months with a mean survival
      of 5 months and in the diastolic dysfunction group 5 patients (28%) died within
      18 months with a mean survival of 12 months.

PMID- 10067037
TI  - Effect of chronic peritoneal fluid eosinophilia on peritoneal membrane function.
AB  - This study was undertaken to evaluate the effects of long-term persistent
      peritoneal fluid eosinophilia on the peritoneal membrane as reflected by a change
      in dialysis function. This was a prospective study undertaken at a community
      based peritoneal dialysis unit, where thirty-one patients were enrolled over a 9
      month period. Chronic, long-term peritoneal fluid eosinophilia was noted in 12/31
      (38.7%) patients. Significant differences were not noted between values of
      creatinine clearance, D/P urea and Kt/V, compared to their baseline values. This
      study shows that long-term peritoneal fluid eosinophilia does not significantly
      affect peritoneal membrane function in patients on maintenance peritoneal
      dialysis.

PMID- 10067038
TI  - Epidemiology and clinicopathologic characteristics of childhood nephrotic
      syndrome in Benin-City, Nigeria.
AB  - Medical records of 58 children, 38 (65.5%) males and 20 (34.5%) females with
      nephrotic syndrome (NS) admitted to the paediatric wards of the University of
      Benin Teaching Hospital (UBTH) Benin-City, Nigeria, between January, 1991 and
      December, 1995 were reviewed. The aim of the study was to document the
      epidemiologic as well as certain clinico-pathologic characteristics of the
      disease in Benin-City. More males than females (ratio of 1.9:1) and older
      children (mean +/- (SEM) 8.2 +/- 0.5 years; range 2-15 years) were affected.
      About 62% of the patients were aged 7 years and above. There was a high incidence
      of hypertension (41.4%) and microscopic haematuria (60%) in the patients.
      Hypercholesterolaemia and hypoalbuminaemia were seen in only 21.6% and 30.2% of
      evaluated patients respectively. Hypercholesterolaemia and hypoalbuminaemia as
      diagnostic criteria for NS in our locale may not be very useful. About 51.7% of
      patients responded to the initial course of prednisolone, out of whom 43.3%
      relapsed (26.7%) frequently and 16.7% infrequently. Mortality rate was 6.9%.
      Urinary tract infection (UTI) occurred in 44.8% of the patients and was caused
      largely by Staphylococcus aureus and untyped coliform organisms.

PMID- 10067039
TI  - Could conductivity be used as a parameter in urinalysis?
AB  - Conductivity is a non-linear function of electrolyte concentration in solutions
      and could be used as an indirect method. The aim of this study was to determine
      the feasibility of urine conductivity measurement, which is a simple, cheap and
      not time consuming method, in the evaluation of renal functions. Seventy-two
      patients whose primary diseases were not taken into consideration were enrolled
      in this study. First morning urine specimens were obtained from all the patients
      and evaluated for osmolality, conductivity, pH, specific gravity, protein,
      creatinine, urea, uric acid, glucose, sodium, potassium, chloride, inorganic
      phosphate and calcium levels. There was a significant positive relation between
      osmolality and creatinine, urea, sodium, potassium, chloride, inorganic
      phosphate, uric acid, conductivity and specific gravity. Conductivity was also
      determined to be positively related to osmolality (r: 0.390, p < 0.01), sodium
      (r: 0.326, p < 0.01) and uric acid (r: 0.345, p < 0.01). The patients were
      grouped as those with a urine osmolality of less or more than 290 m Osm/kg. H2O
      (group A and B respectively). Urine conductivity was 6.84 +/- 5.35 (0.16-23.2)
      mScm-1 in group A and 10.6 +/- 5.25 (0.12-192) mScm-1 in group B. The difference
      was statistically significant (p = 0.005). When the spectrum of conductivity
      values were evaluated separately in each group, 74% of the patients in group A
      and 33.9% of the patients in group B were determined to have a conductivity level
      of less than 7.338 mScm-1. In conclusion, urine conductivity has a positive
      relation with osmolality. In addition, while osmolality and specific gravity are
      effected by many non-electrolyte molecules, conductivity is only related to
      sodium and uric acid concentrations. In addition, urine osmolality and
      conductivity levels could be used to interpret the concentration of uncharged
      glucose molecules. These results suggest that conductivity could be used as a
      parameter in routine urinalysis.

PMID- 10067040
TI  - Population based data on urinary excretion of various metabolites in children of
      north western region of Pakistan.
AB  - Population based data on urinary excretion of various metabolites of pathological
      importance, Calcium, Magnesium, Sodium, Potassium, Oxalates, Citrates,
      Phosphates, Uric acid and urea have been collected from around three hundred
      children of the Quetta valley. The body weight was in the range of 11-50 kg and
      the age was in between 4-16 years. The urine excretion average was 987.5 +/-
      452.5 ml per 24 hours. There was 11.5% incidence of hypercalciuria, 8.5%
      incidence of hyperuricosuria, 2.0% hyperphosphaturia, 2.5% hypomagnesuria, 3.5%
      hypocitraturia, 6.5% hypernatriuria, 43.5% hypokaliurea and 2.1% hyperoxaluria.
      Urea excretion average was 23.11 +/- 14.99 g per 24 hours. The study provided the
      basis for childhood reference pattern in urinary excretion of compounds related
      to various pathological conditions, in particular stone formation in this region.

PMID- 10067041
TI  - Effect of dialysis on bleeding time in chronic renal failure.
AB  - Renal failure is associated with severe haemorrhagic complications. Platelets
      play an important role in coagulation and their dysfunction may be responsible
      for the bleeding tendency in these patients. Sixty patients with advanced renal
      failure were investigated for bleeding tendency due to platelet dysfunction. The
      pre-dialysis platelet count was 46 to 325 x 10(9)/L) (mean 166 x 10(9)/L). Post
      dialysis platelet count was 60 to 310 x 10(9)/L, (mean 172 x 10(9)/L) Pre
      dialysis mean bleeding time (BT) was 4.95 +/- 0.27 minutes (range 1.30 to 20
      minutes). Thirty-three patients (55%) had prolonged BT before dialysis. Mean BT
      in all patients after dialysis was 2.46 +/- 0.24 minutes (range 1.15 to 10
      minutes). BT was corrected in 27 (81.8%) out of 33 patients with prolonged BT
      before dialysis. In 6 patients (10%) it remained prolonged. This improvement in
      BT after dialysis was statistically significant (p value < 0.001). Both
      peritoneal and hemodialysis resulted in significant improvement in bleeding time.

PMID- 10067042
TI  - Esophageal variceal banding--the local experience.
AB  - Banding of esophageal varices was done in 29 patients suffering from acute
      variceal bleeding. In 13 patients this was the first bleed while in 16 it was
      recurrent. Five patients had large grade III (polypoid) varices while others had
      grade II varices. Banding was done using multi band ligator and 4-6 bands were
      fired per session. Repeat endoscopy at 3 weeks revealed persistence of varices
      requiring second session of banding in 11 cases and small varices (difficult to
      band) in 9 cases. Two patients expired due to persistent bleeding and 2 bled from
      esophageal ulcers. Both patients settled with conservative treatment. A third
      session of banding was required in 5 cases only. None of the cases developed any
      major complication. In our setting where expertise for sclerotherapy is scarce
      and cost of sclerosants is high; banding appears to be a cost effective modality
      for the management of variceal bleeding with a low complication rate.

PMID- 10067043
TI  - Magnesium in health and disease.
AB  - This paper reviews the significance of magnesium (Mg) in health and disease. Mg
      is an intracellular element and after potassium, second most abundant cation
      found within the cell. Plasma contains less than 1% of body's total Mg.
      Physiologically most active form of Mg is ionized form. Most of the plasma Mg is
      bound with albumin, globulin and proteins. This bound form of Mg is not available
      for biochemical actions. Binding of Mg with the specific globulin fractions may
      be indicative of certain disease patterns. Deficient serum Mg concentration may
      be a sign of various pathologies. Thus, the repletion of Mg may be helpful in the
      treatment of diseases such as hypertension, acute myocardial infarction and
      atherosclerosis. Role of Mg for the treatment of chronic disease, however, is
      poorly understood and requires a better knowledge of ionized Mg metabolism.

PMID- 10067044
TI  - Pregnancy unmasking hypoparathyroidism.

PMID- 10067045
TI  - Nocturnal enuresis in children.
AB  - This common condition can be managed by the general practitioners. The key answer
      to nocturnal enuresis is nocturnal self-awakening and recently more emphasis is
      given on this which is an area of greatest promise. Behavioural modification in
      conjunction with an enuretic alarm also teaches this skill and has the highest
      cure rate and the lowest relapse rate. Enuretic alarms can be used any time from
      age 5 onwards. But drugs are only indicated when there is need for short term
      dryness e.g. when the child has to be away from home.

PMID- 10067046
TI  - Evaluation of chest pain in general practice.

PMID- 10067047
TI  - Helicobacter pylori: a review.

PMID- 10067048
TI  - WebReview green monkeys--Pakistan Public Health Forum
      http:/(/)www.greenmonkeys.net.

PMID- 10067049
TI  - Prevalence of hepatitis B Virus in dental clinics in Rawalpindi/Islamabad.

PMID- 10067050
TI  - [Tuberculosis sequelae in Japan].
AB  - Tuberculosis had been the leading cause of death in Japan until 1950, and in
      these days there were about 3 million patients with active tuberculosis every
      year. From about 1950 to 1960 surgery was the treatment of choice if there were
      cavities and the lesions were regional. The number of patients who had
      thoracoplasties and/or pulmonary resections at national sanatoriums during the
      period of 1954 to 1961 was about 200,000. Since national sanatoriums had about
      25% of the total beds for tuberculosis in Japan at that time, the total number of
      surgically treated patients would be around four times this number, that is 0.8
      to 1.0 million. Many of those who survived suffered later from complications,
      which included chronic respiratory failures, chronic hepatitis (hepatitis C),
      liver cirrhosis and/or hepatic cell carcinomas. There are at least 50,000
      patients who are under home oxygen therapy (HOT) in Japan, of whom about 30% are
      those with pulmonary tuberculosis sequelae (TBS). The survival rate after the
      start of HOT in these patients was found better in those who had surgical
      treatments than in those who had medical treatments only. Since hypercapnea was
      more common in the former, better survival rates in the hypercapnic than in the
      normocapnic patients with TBS as a whole could be due to the fact that more of
      the surgically treated patients were included in the hypercapnic group. For this
      reason, it is premature to conclude that hypercapnea is an independent favorable
      prognostic factor in TBS patients with chronic respiratory failure. Because more
      than one-forth of thoracoplasties and/or pulmonary resections were done in
      national sanatoriums, it is the responsibility of those who are now working in
      national hospitals to treat and support these patients with TBS who developed
      complications such as respiratory failures, chronic hepatitis, liver cirrhosis,
      and/or hepatic cell carcinomas.

PMID- 10067051
TI  - [Investigation of pulmonary hemodynamics and chest X-ray findings in patients
      with pulmonary tuberculosis sequelae and obstructive ventilatory impairment].
AB  - We investigated pulmonary hemodynamics and chest X-ray findings to explore
      significance of obstructive ventilatory impairment in patients with pulmonary
      tuberculosis sequelae. One hundred and two patients underwent examinations of
      blood gases, spirometry, and right cardiac catheterization. The patients were
      divided into two groups, according to forced expiratory volume in one second as
      the percentage of forced vital capacity (FVC), which was expressed as FEV1%.
      Group A (n = 38) had FEV1% of 55% or lower and Group B (n = 64), FEV1% above 55%.
      First, the values of blood gases and hemodynamics were compared between the two
      groups, regarding the percent predicted value of FVC as a covariate. Secondly,
      between 26 of Group A and 42 of Group B, the change of pulmonary arteriolar
      resistance (PAR) before and after 100% oxygen breathing for 10 minutes was
      compared. These comparisons were made by exploratory data analysis. Lastly, we
      described every case with five items of chest X-ray findings and the extent of
      each finding we had defined. The items were emphysematous change; fibrosis,
      bronchiectasis and/or cavity; pulmonary resection and/or atelectasis; pleural
      thickening; and thoracoplasty. We explored X-ray findings influenced on airway
      obstruction by ridit (abbreviation for "relative to an identified distribution")
      analysis, taking smoking status into consideration. The results were as follows.
      (1) The patients of Group A tended to show severer hypoxemia and tissue hypoxia
      than the patients of Group B. (2) The patients of Group A tended to show worse
      values of pulmonary hemodynamics than the patients of Group B. Under an even
      level of the arterial oxygen tension that was 60 Torr or lower, pulmonary artery
      mean pressure was higher in Group A than in Group B. (3) PAR after oxygen
      breathing was less likely to decrease in Group A than in Group B. (4) As any mean
      ridit was standardized and adjusted to 0.5 in Group B, every mean ridit of
      "emphysematous change" in Group A was the largest-0.63 in non-smokers, 0.74 in ex
      smokers and 0.70 in current smokers. Therefore, "emphysematous change" was more
      influenced on airway obstruction than any other finding because of the largest
      mean ridit. We conclude as follows. Pulmonary hypertension is more serious in
      patients suffering from severe airway obstruction with pulmonary tuberculosis
      sequelae, and it may be attributable to reduction in capacity of anatomical
      pulmonary vascular bed rather than hypoxic pulmonary vasoconstriction.
      Pathological changes such as "emphysematous change" on the radiograph might be
      considered as an important cause of obstructive ventilatory impairment.

PMID- 10067052
TI  - [Evaluation of Mycobacterium kansasii isolates from a clinical laboratory in a
      city hospital].
AB  - Fifteen isolates of Mycobacterium kansasii in Showa University Fujigaoka Hospital
      between 1982 and 1995 were investigated. Comparing by gender, 13 were isolated
      from male patients and only two were isolated from female patients. The average
      of cases was 48 years old and 14 out of 15 cases (93%) were isolated from
      respiratory tract specimens. The rate of the smear- and culture-positives was
      64%, which was significantly higher than that (26%) of M. avium complex (p < 0.01
      by chi 2 test). All 4 isolates were susceptible to rifampicin (10 micrograms/ml)
      by drug susceptibility testing using Ogawa egg medium, and only 1 was resistant
      to ethambutol (2.5 micrograms/ml). Seven out of 10 patients whose medical record
      was available were diagnosed as pulmonary infection with M. kansasii. Two out of
      4 patients with primary infection type had underlying diseases such as diabetes
      mellitus and leukemia, while the remaining two patients did not have any
      underlying disease. Two out of 3 patients with secondary infection type had a
      medical history of tuberculosis and the remaining 1 patient had infected
      pulmonary cyst. Such as Pseudomonas aeruginosa, Enterobacter aerogenes and
      Flavobacterium spp., and Branhamella catarrhalis, associated with M. kansasii,
      bacteria more than 10(7) cfu/ml were isolated from the sputa of 3 patients with
      leukemia, infected pulmonary cyst and post-tuberculosis, respectively. M.
      kansasii, Stenotrophomonas maltophilia (10(7) cfu/ml) and Candida albicans were
      detected from the sputum of 1 patient with nephrosis, for which steroid
      (predonin) and antibiotics (piperacillin and latamoxef) were administrated,
      however, this patient was not diagnosed as a case of M. kansasii infection. These
      findings suggest the fact that M. kansasii inhabits among compromised hosts of a
      city hospital.

PMID- 10067053
TI  - [Tuberculous meningitis developed during treatment for systemic lupus
      erythematosus (SLE)].
AB  - A 51-year-old woman was admitted to our hospital complaining of fever and general
      fatigue. Physical examination revealed butterfly-like erythema in face, facial
      edema and diffuse purpura all over her body. Laboratory data showed renal
      dysfunction, nephrotic syndrome and active phase of SLE. She was administered
      first methylprednisolone (1g/day/3 days by intravenous drip) then prednisolone
      (60 mg/day/month, orally) and had immune adsorption therapy for eight times.
      However, 14 days after the last session of immune adsorption, she developed fever
      of 39 degrees C and mild headache, and then 3 days later, she gradually became
      unconscious. Brain CT showed hydrocephalus. We diagnosed her as having
      tuberculous meningitis based on the detection of acid-fast bacillus in
      cerebrospinal fluid, and began treatment with antituberculous agents. We
      suspected that tuberculous meningitis had caused hydrocephalus. We tried
      percutaneous drainage of the left ventricle for hydrocephalus. Brain MRI showed a
      tuberculoma depicted as a mass of low intensity in the right cerebellum on the T1
      weighted image, and of high intensity on the T2-weighted image, and the meninx in
      the basal cistern was enhanced. After treatment with antituberculous agents, we
      performed serial brain MRI and examined cerebrospinal adenosine deaminase
      activity (ADA). Despite treatment with antituberculous agents, new intracerebral
      tuberculomas had developed in some areas, whereas they had disappeared in other
      areas. After treatment for 4 months, the level of cerebrospinal ADA became
      normal, and the patient recovered consciousness despite the presence of multiple
      tuberculomas. Both the cell counts and the level of ADA in cerebrospinal fluid
      are the good indicators of the activity of tuberculous meningitis and reflected
      its clinical course. Furthermore, the level of ADA in cerebrospinal fluid changed
      with brain MRI image. Serial brain MRI and examination of ADA in cerebrospinal
      fluid were useful to know the activity of tuberculous meningitis and to evaluate
      the response to treatment.

PMID- 10067054
TI  - [Drug-induced pneumonitis].
AB  - Drug can cause various types of lung damages, with drug-induced pneumonitis
      (including acute interstitial pneumonia, usual interstitial pneumonia,
      desquamative interstitial pneumonia, nonspecific interstitial pneumonia,
      bronchiolitis obliterans with organizing pneumonia, eosinophilic pneumonia and
      hypersensitivity pneumonitis) being the most important among them. The incidence
      and the causative agents of drug induced pneumonitis have varied over time.
      Before 1980, anticancer agents and gold salts were the main drugs, and the number
      of causative drugs (61) and case reports was small. Recently, pneumonitis has
      increasingly been caused by Chinese herbal medicines, antibiotics, chemotherapy
      agents, anti-inflammatory drugs, analgesics, cytokines, and gold salts, and the
      number of case reports and drugs involved (177) has increased. Drug-induced
      pneumonitis has characteristics that depend on the causative agent. Review of our
      patients and reports in Japan revealed the following. Pneumonitis caused by anti
      inflammatory drugs, analgesics, and antibiotics generally develops at 1-2 weeks
      after starting administration, and bronchoalveolar lavage and histologic
      examination of lung biopsies reveals the features of eosinophilic pneumonia. Such
      pneumonitis is associated with a high frequency of a positive drug lymphocyte
      stimulation test (DLST), and has a good outcome. Conversely, with pneumonitis
      caused by anticancer and immunosuppressive agents, the onset is often delayed and
      the disease has features of diffuse interstitial pneumonia and pulmonary
      fibrosis. The frequency of a positive DLST is low, and the outcome is generally
      poor. Pneumonitis induced by Chinese herbal medicines, gold salts, and
      antituberculosis agents has intermediate features between the above two types
      :i.e., it develops after 2-3 months or six months (gold salts), and resembles
      either eosinophilic pneumonia, BOOP or interstitial pneumonia. For in vitro
      identification of causative drugs, the DLST and the leukocyte migration
      inhibition test (LMIT) are generally used. The latter test is superior in
      sensitivity, suggesting that the mechanism of this test involves cytokines such
      as IL-1 alpha, IL-1 beta, IL-2, TNF-alpha, and IL-8.

PMID- 10067055
TI  - [View of development of fluoroquinolones].
AB  - The global resurgence of tuberculosis and the emergence of multidrug-resistant
      tuberculosis have emphasized an urgent need for new, effective antimycobacterial
      drugs. A new antimycobacterial drugs should have a different mechanism of action
      to the standard drugs and should not show cross-resistance with them. Favorable
      pharmacokinetic properties, low incidence of side effects and low cost are the
      characteristics that would make antimycobacterial drugs suitable for extensive
      use. The fluoroquinolones would appear to fulfill most of the criteria for an
      ideal class of antimycobacterial drugs. The fluoroquinolones have been proposed
      for the treatment of Mycobacterium tuberculosis (M. tuberculosis) infections,
      with the results of in vitro, animal model and clinical studies suggesting that
      ofloxacin, ciprofloxacin, sparfloxacin and levofloxacin are the most promising of
      these drugs. However, these fluoroquinolones should not be used as first-line
      drugs, but rather, they should be reserved for treatment of tuberculosis that is
      resistant to rifampicin and isoniazid. Recently, a new investigational
      fluoroquinolone derivative, AM-1155, DU-6859a and CS-940, have excellent in vitro
      activity against M. tuberculosis, further studies are required to assess its
      clinical activity. We discussed the future of view of development of
      fluoroquinolones for mycobacterial diseases on the basis of structure-activity
      and structure-side-effect relationship studies. The comparative analysis enabled
      us to elucidate the structural requirements for the antimycobacterial activity
      and side-effects of fluoroquinolones. In addition, we summarized the newer
      methods for high-throughput screening of compounds against M. tuberculosis and
      discussed the problem of development of fluoroquinolones for mycobacterial
      diseases.

PMID- 10067056
TI  - [Current status and perspectives on the development of rifamycin derivative
      antibiotics].
AB  - Rifampicin (RFP) was developed as one of the anti-tuberculosis drugs in 1966 and
      has been used for almost 30 years. Establishment of combination therapy using RFP
      has been contributing to the treatment/eradication of tuberculosis. A number of
      rifamycin derivatives, as post RFPs, have been synthesized/developed over the the
      years. Chemical modification of rifamycins has largely been concentrated on the
      moiety of naphthalene ring because modification of the ansa chain moiety reduces
      the activity. In 1992, rifabutin was approved as a preventive drug for MAC
      infection in AIDS patients in the United States and in European countries. It is
      noteworthy that rifapentine (RPT) was approved as an anti-tuberculosis drug in
      1998 by FDA in the United States. A newly synthesized rifamycin derivative (KRM
      1648, rifalazil) possesses a potent activity against both M. Tuberculosis and
      MAC, and it is now under clinical trial for the treatment of Tuberculosis in the
      United States. KRM-1648 is metabolized to 30-hydroxy KRM and 25-deacetyl KRM in
      the body, and its 30-hydroxylation is caused by liver cytochrome P450 3A. It is
      well known that RFP, RFB and RPT induce liver cytochrome P450 in animals and
      human, and these accelerate the metabolism of concomitant drugs such as HIV
      protease inhibitors resulting in lowering their blood levels. While KRM-1648 did
      not induce liver P450 in animals, but it is not examined yet in human. Clinical
      study of DOT with intermittent therapy of RPT in combination with INH resulted in
      the preferable therapeutic effect comparable to the RFP therapy. Since KRM-1648
      has a potent activity, a high tissue distribution and a long half-life, it may be
      also suitable for intermittent therapy. For the future novel anti-tuberculosis
      drugs and therapy for tuberculosis, it is prerequisite to develop new drugs with
      a preferable antimicrobial activity, to shorten further the treatment period, and
      to be effective against multi-drug resistant bacilli. It is expected that more
      effective novel rifamycin derivatives can be developed with the above view
      points.

PMID- 10067057
TI  - [In vitro antimicrobial activities of quinolones, rifamycins and macrolides
      against Mycobacterium tuberculosis and M.avium complex: attempt to establish new
      assay methods which accurately reflect therapeutic effects of test agents in
      vivo].
AB  - Profiles of expression of the antimicrobial activities of LVFX, KRM-1648 (KRM),
      and CAM against M. tuberculosis (MTB) and M. avium complex (MAC) residing in MONO
      MAC-6 human macrophage like cells (MM6-M phi s) and A-549 human type II alveolar
      pneumocyte cells (A-549 cells) were determined. First, the antimicrobial
      activities of LVFX, KRM, and CAM against intracellular organisms of MTB Kurono
      and MAC N-444 strains were examined under conditions in which infected MM6-M phi
      s and A-549 cells were cultured for up to 7 days or longer in medium containing
      the antimicrobials at their Cmaxs in the blood, achievable after oral
      administration of clinical dosages of these drugs. The antimicrobial effects of
      LVFX and KRM against respectively MTB and MAC within A-549 cells were
      significantly less than the activities they displayed against the same organisms
      residing in MM6-M phi s. Notably, it was also found that KRM had a markedly
      larger MIC (0.25 microgram/ml) for MAC N-444 within A-549 cells than its MIC
      (0.008 microgram/ml) for the same strain residing in MM6-M phi s. Thus, the
      profiles of LVFX- and KRM-mediated killing or inhibition of intracellular MTB or
      MAC organisms in A-549 cells were markedly different from those observed for the
      organisms residing in MM6-M phi s. Second, invasive and multiplicative phenotypes
      of MTB and MAC organisms, which had been adapted to either an extracellular or
      intracellular environment (designated as E- and I-type organisms, respectively),
      were studied. In the case of MTB, I-type organisms (retrieved from infected MM6-M
      phi s after bacterial growth within the M phi s during 5-day cultivation) were
      less efficient than E-type organisms (prepared by cultivating the organisms in
      7H9 medium) in entering MM6-M phi s, whereas I-type organisms were more efficient
      than E-type organisms in invading A-549 cells. On the other hand, in the case of
      MAC, infectivity of I-type organisms not only in MM6-M phi s but also in A-549
      cells was larger than that of E-type organisms. Next, while I-type organisms of
      MTB and MAC displayed more vigorous replication within MM6-M phi s than E-type
      organisms, the growth rate of E-type organisms within A-549 cells was more rapid
      than that of I-type organisms residing in A-549 cells. These findings indicate
      that there are significant differences between E- and I-type organisms of MTB or
      MAC in ability to invade and multiply within M phi s (professional phagocytes)
      and alveolar epithelial cells (nonprofessional phagocytic cells).

PMID- 10067058
TI  - [Clinical evaluation of new quinolones as antituberculosis drugs].
AB  - Compared with the recent rapid advances in the diagnosis of tuberculosis,
      advances in the treatment of tuberculosis have been quite slow. For example, as
      long as six months are required for initial treatment, even with addition of
      pyrazinamide in the first two months to isoniazid, rifampicin, and streptomycin
      or ethambutol. Moreover, it is not always easy to treat patients who cannot
      receive standard agents including isoniazid and rifampicin due to adverse effects
      of these drugs or drug resistance. For these reasons, the development of new
      agents with potent antituberculosis activities and fewer adverse effects is
      urgently desired. However, at present, few new antituberculosis agents are being
      developed, and new quinolones are considered the most promising new
      antituberculosis agents due to their lack of cross-resistance to previously
      existing antituberculosis agents, their excellent in vitro and in vivo
      antituberculous activities, and good pharmacokinetics. We therefore reviewed
      experimental studies and clinical reports useful for evaluation of potential
      clinical use of new quinolones as antituberculosis drugs. Our conclusions are
      summarized below: 1) Of nine new quinolones on the market, ofloxacin,
      ciprofloxacin, aparfloxacin and levofloxacin have excellent in vitro and in vivo
      antituberculous activities without cross-resistance to previously existing
      antituberculosis agents. 2) Ofloxacin appears to be useful clinically for
      intractable multidrug-resistant tuberculosis. The incidence and severity of
      adverse effects of ofloxacin were very low on longterm administration. 3)
      Ofloxacin resistance emerged from two to four months after initiation of
      administration of ofloxacin, and ofloxacin exhibited cross-resistance to other
      new quinolones. 4) The usefulness of new quinolones for initial treatment of
      tuberculosis is unclear. 5) New quinolones should be used to treat patients with
      drug-resistant tuberculosis and those patients for whom adverse effects have
      limited the use of standard agents. However, monotherapy with new quinolones is
      not recommended, due to the significant risk of emergence of quinolone
      resistance. 6) Not only ofloxacin, ciprofloxacin, sparfloxacin and levofloxacin,
      which are on the market, but also gatifloxacin, CS-940, Du-6859a and other newly
      developed new quinolones are candidates for new antituberculosis agents. However,
      careful study not only of antituberculous activities and pharmacokinetic but also
      drug interactions and chronic cumulative toxicities due to long-term
      administration are needed prior to clinical application of these drugs.

PMID- 10067059
TI  - [The need for new antituberculosis agents in Japan].
AB  - We discussed the need of new antituberculosis agents in Japan concerning drug
      adverse reactions in particular as well as drug interactions and drug resistance.
      We reviewed medical charts of hospitalized patients receiving standard
      antituberculosis chemotherapy (INH + RFP + EB/SM +/- PZA), and analyzed all
      symptoms, signs and abnormal laboratory data presumably caused by the
      chemotherapy. About 48% of 228 cases analyzed had at least 1 episode of adverse
      reactions: 77 episodes of hepatotoxicity, 15 episodes of ototoxicity, 14 episodes
      of eruption, 14 episodes of ocular toxicity and so on. About 23% cases treated
      with RFP, 20% cases with SM, 12% cases with INH and 7.7% cases with EB had at
      least 1 episode of adverse reactions due to the corresponding agent. In 59 cases,
      at least one agent was stopped to administer because of adverse reactions.
      Finally, standard chemotherapy could not be completed in 23% of all cases, and in
      stead, the other agents, mainly new quinolones, were administered. RFP induces
      cytochrome P450 3A in the liver to decrease the activities of many drugs, such as
      cyclosporin A, tacrolimus, protease inhibitor, itraconazole, and clarithromycin.
      In some clinical settings, RFP cannot be administered in combination with such
      drugs. In conclusions, new antituberculosis agents that have strong activities
      with less adverse reactions and drug interactions are needed in Japan, even
      without considering drug resistance.

PMID- 10067060
TI  - [Morphological characteristics of epithelial cell line from rat cornea].
AB  - PURPOSE: Morphological characteristics of established cell line (RtCE) derived
      from rat anterior corneal epithelium. MATERIAL AND METHODS: Morphology of
      cultured RtCE cells was evaluated by light and electron microscopy. Anterior
      corneal epithelium of rat served as control. RESULTS: Both in light and electron
      microscope we observed morphological similarity with anterior corneal epithelium
      (several layers of cells, numerous desmosomal connections). Moreover, similar
      morphological changes were observed in relation to the control material, i.e.
      degeneration and flattening of cells in superficial layers. CONCLUSIONS: The
      morphological analysis of RtCE cell line proves its usefulness for further
      cytomorphological, cytogenetical and functional analyses, as well as for
      evaluation of influence of different physico-chemical and biological factors on
      growth and regeneration of corneal epithelium in vitro.

PMID- 10067062
TI  - [Corneal topography before and after radial keratotomy].
AB  - PURPOSE: Evaluation of corneal topography of patients examined before and after
      radial keratotomy. MATERIAL AND METHODS: There were 23 patients (40 eyes)
      examined at our department. The corneal shape was evaluated by use of EYE-SYS
      company equipment. RESULTS: Postoperatively marked flattening of the central
      cornea was noticed with hypercorrection which decreased during postoperative
      period up to six months. Good postoperative results persisted after 18 months.
      Additional corneal incisions during RK decreased astigmatism effectively.
      CONCLUSION: Examination and corneal shape analysis before and after RK enabled an
      objective and quantitative evaluation of this procedure.

PMID- 10067063
TI  - [Fluorophotometric study of juvenile insulin-dependent diabetic patients].
AB  - PURPOSE: The aim of this study is to find a correlation between fluorophotometric
      data, diabetes duration and patient's age. MATERIALS AND METHODS: A group of 19
      patients (38 eyes) aged 11-23 years with juvenile-onset, insulin-dependent
      diabetes, treated for 2-17 years were examined using ocular fluorophotometry.
      Visual acuity, anterior segment and fundus as well as IOP, fluoroangiography and
      opacimetry were also examined. RESULTS: Anterior Chamber (AC) and Posterior
      Vitreous (PV) fluorescein concentration was higher in the group with mild
      background retinopathy (10 eyes) than in group with normal fundi (28 eyes).
      CONCLUSIONS: Diabetes duration over 15 years increases the risk of the
      development of diabetic retinopathy and increases fluorescein leakage through the
      blood-retinal barrier in juvenile insulin-dependent diabetes patients.

PMID- 10067064
TI  - [Pathomorphological evaluation of the extraocular muscles during strabismus].
AB  - PURPOSE: An analysis of the histopathological picture of extraocular muscles
      removed in the operation of strabismus. MATERIAL AND METHODS: Light microscopy
      analysis included 131 fragments of rectus muscles, with the majority of lateral,
      collected from patients with concomitant squint of different angles and disease
      durations. RESULTS: Normotopic cross-striated muscle fibres were observed in 40
      (30.6%) studied muscles, while pathological changes appeared in 91 (69.4%)
      muscles with a prevailance of fibrous atrophy. A correlation was found between
      the histopathological picture of the examined muscles and the extent of
      strabismus. CONCLUSIONS: Pathomorphological changes were observed with the
      majority of the extraocular muscles in the microscopic picture. The observed
      changes in the cellular structure of the extraocular muscles influenced the
      extent of the squint angle, affecting the result of surgery.

PMID- 10067065
TI  - [The results of surgery on squint with pathological muscle attachment].
AB  - The aim of our study was to evaluate the results of the operation on squint with
      pathological attachment of lateral rectus revealed during surgery. MATERIAL AND
      METHODS: The study involved 22 children (12 girls and 10 boys) out of 320
      children operated on for squint in the years 1993-1996, who had pathological
      attachment of lateral rectus. Alternating convergent squint was found in 12
      children, unilateral in 10. Muscle exposure showed dislocation of lateral rectus
      attachment--upwards by c. 1.5 mm in 11 children, downwards and obliquely by c. 2
      mm in 10 children, in 1 child the upper part of the attachment was shifted
      forward by 1 mm. During the surgery, in addition to the reduction of squint
      angle, physiological attachment of the rectus was reconstructed. RESULTS: The
      operation restored parallel position of the eyes in 22 children, very good vision
      was obtained in 12 (54%) with alternating convergent squint, significant
      improvement in 5 (22%) with unilateral convergent squint, and only slight
      improvement in the remaining 5 (22.7%) with high initial amblyopia and squint
      angle from +15 degrees to +30 degrees.

PMID- 10067066
TI  - [Results of surgical treatment of divergent squint in the author's patients].
AB  - The results of surgical treatment of divergent squint in 97 patients were
      analysed. The results obtained directly after the operation were compared with
      the results of examinations conducted on the average 6 years after the surgery
      operation. Their durability has been estimated for the cases of fixed and
      periodic divergent squint. After surgical treatment of divergent squint the
      parallel position of the eyes was obtained in 72% of patients and the result was
      permanent in most cases. Thanks to the liquidation of squint angle the
      convergence and binocular vision improved (the fusion improved in 50% of cases).
      The convergence and binocular vision continued to ameliorate between the
      operation and the final examination, especially in the cases in which surgical
      treatment gave the parallel position of the eyes (the fusion kept improving in
      73% and stereopsis in 41% of cases).

PMID- 10067067
TI  - [New view on the causes and treatment of Brown's syndrome].
AB  - The cause of the Brown's syndrome has so far been assigned to changes in the
      tendon sheath. Muhlendyck has proved that in Brown's syndrome patients the tendon
      sheath is regular whereas the symptoms are caused by changes in muscle obliquus
      superior or in the trochlea area. Resection of the irregular structures results
      in a normalisation of the active and passive elevation in adduction. 18 patients
      have been operated at our department according to the Muhlendyck method. Early
      postsurgical observations suggest positive results.

PMID- 10067068
TI  - [Our results of orbital fracture treatment].
AB  - PURPOSE: To present our results of orbital fracture treatment. MATERIAL AND
      METHODS: There were 28 patients with orbital fracture hospitalized at
      Ophthalmology Department of Medical University in Gdansk during last 5 years.
      Most of them had a blow-out fracture type. We reconstructed it using artificial
      materials (cranioplast). It was shaped according to the defect of the bone.
      Fracture of zygomatico-frontalis and zygomatico-maxillaris suture was fixed by
      bone sutures. The same method was used to treat gaps in medial and superior wall
      of the orbit. RESULTS AND CONCLUSIONS: We took into consideration the period of
      time between the trauma and surgical procedure. Full recovery (lack of diplopia)
      was achieved in 10 cases which underwent operation in less then 14 days after
      trauma and only in 2 cases in the group where patients were operated later than
      14 days after accident.

PMID- 10067069
TI  - [Suspending of blepharoptosis on temporalis fascia slings: our own experience].
AB  - There are many procedures providing treatment of ptosis. In cases with palpebrae
      levator palsy, procedures involving mechanical suspension of palpebrae are used.
      Artificial and natural materials are used to suspend the lid. We describe
      surgical treatment of blepharoptosis using autogenous temporalis fascia sling.
      The sling is attached to the tarsus and spreads to the frontalis muscle. We have
      used this procedure in 12 cases. Full effect of functional elevation of palpebrae
      was achieved in 14 to 30 days after procedure. We did not encounter any
      significant complications due to this material. These operative modifications
      make this procedure more closely parallel to the normal eyelid dynamics and
      provide consistently good results for this difficult problem.

PMID- 10067071
TI  - [A case of bird-shot type chorioretinopathy].
AB  - A case of a 39-years-old man with progressive deterioration of visual acuity,
      which occurred during the birdshot chorioretinopathy, is presented. The major
      findings in this rare disorder concern the ocular fundus. The most marked are the
      patterned distribution of depigmented spots without hyperpigmentation, radiation
      from the optic disc in association with vitritis, retinal vasculopathy with
      frequent cystoid macular oedema, and involvement of the optic nerve head. HLA
      testing showed very strong disease association with HLA-A 29 (95.8%).

PMID- 10067072
TI  - [The significance and interpretation of the electrophysiological and
      psychophysiological analyses in the diagnosis of glaucoma].
AB  - The goal of this paper is to discuss and indicate which electrophysiological and
      psychophysical tests are useful for diagnosis and monitoring of glaucoma
      patients. In diagnosis of glaucoma, among electrophysiological methods, the
      authors perform mainly transient and steady-state pattern electroretinogram
      (PERG). Steady-state as well as transient PERG have the best sensitivity and
      specificity in diagnosis of this disease even in its early stages. Pattern visual
      evoked potentials (PVEPs) are less sensitive and specific, that is why this
      examination is rare in practical use. The authors describe the method of PERG,
      discuss most frequent mistakes in the method and interpretation of the obtained
      results. Among psychophysical tests the authors emphasize the significance of
      short-wave-length perimetry (blue-on-yellow) and standard static perimetry in
      early diagnosis of glaucoma. On the basis of literature, the authors present also
      other psychophysical methods, which can be applied in diagnosis of glaucoma.

PMID- 10067073
TI  - [Discovering phenomena leading to the death of retinal ganglion cells in
      glaucoma: the aim of ophthalmology at the end of the 20th century. (The report
      introducing the 1st Glaucoma Symposium organized by Glaucoma Section of POS --
      Wroclaw, April 17-18, 1998)].

PMID- 10067074
TI  - The differential infectivity and staged progression models for the transmission
      of HIV.
AB  - Recent studies of HIV RNA in infected individuals show that viral levels vary
      widely between individuals and within the same individual over time. Individuals
      with higher viral loads during the chronic phase tend to develop AIDS more
      rapidly. If RNA levels are correlated with infectiousness, these variations
      explain puzzling results from HIV transmission studies and suggest that a small
      subset of infected people may be responsible for a disproportionate number of
      infections. We use two simple models to study the impact of variations in
      infectiousness. In the first model, we account for different levels of virus
      between individuals during the chronic phase of infection, and the increase in
      the average time from infection to AIDS that goes along with a decreased viral
      load. The second model follows the more standard hypothesis that infected
      individuals progress through a series of infection stages, with the
      infectiousness of a person depending upon his current disease stage. We derive
      and compare threshold conditions for the two models and find explicit formulas of
      their endemic equilibria. We show that formulas for both models can be put into a
      standard form, which allows for a clear interpretation. We define the relative
      impact of each group as the fraction of infections being caused by that group. We
      use these formulas and numerical simulations to examine the relative importance
      of different stages of infection and different chronic levels of virus to the
      spreading of the disease. The acute stage and the most infectious group both
      appear to have a disproportionate effect, especially on the early epidemic.
      Contact tracing to identify super-spreaders and alertness to the symptoms of
      acute HIV infection may both be needed to contain this epidemic.

PMID- 10067075
TI  - On the role of anatomy in learning by the cerebellar cortex.
AB  - The properties due to the location of neurons, synapses, and possibly even
      synaptic channels, in neuron networks are still unknown. Our preliminary results
      suggest that not only the interconnections but also the relative positions of the
      different elements in the network are of importance in the learning process in
      the cerebellar cortex. We have used neural field equations to investigate the
      mechanisms of learning in the hierarchical neural network. The numerical
      resolution of these equations reveals two important properties: (i) The
      hierarchical structure of this network has the expected effect on learning
      because the flow of information at the neuronal level is controlled by the
      heterosynaptic effect through the synaptic density-connectivity function, i.e.
      the action potential field variable is controlled by the synaptic efficacy field
      variable at different points of the neuron. (ii) The geometry of the system
      involves different velocities of propagation along different fibers, i.e.
      different delays between cells, and thus has a stabilizing effect on the
      dynamics, allowing the Purkinje output to reach a given value. The field model
      proposed should be useful in the study of the spatial properties of hierarchical
      biological systems.

PMID- 10067076
TI  - Cluster growth by mitosis.
AB  - A stochastic mitosis growth model is introduced. The colony enlarge by random
      mitosis of a mother cell which is replaced by two daughter cells. Unlike growth
      models based on a grid, the present model is isotropic. Using simulation of
      colonies of 10,000 cells, it is found that the density is constant and the
      boundary is fractal.

PMID- 10067077
TI  - [Dietary habits, lifestyle and physical condition of junior high school
      students].
AB  - Dietary habits, lifestyle and thirty subjective physical symptoms of all students
      at the first year level of junior high school were investigated by means of a
      specially designed questionnaire. After two years, the same questionnaire was
      again used on the same students who were now in their third year of junior high
      school. The students (305 boys and 319 girls totalling 624 students) who were
      included in both the first and the second surveys were used to analyze the
      relationship between physical conditions and lifestyle. The results were as
      follows: 1. The number of subjective symptoms increased significantly during the
      two years. 2. The students in their third year consumed less of a variety of
      foods than those in their first year. Dietary habits such as having a breakfast,
      lunch, or eating a meal with the family were worse at the third year level
      compared to the first year level. 3. In regard to lifestyle, recreational time or
      sleep time decreased while study time, dissatisfaction with life, or the rate of
      getting in or being in trouble increased during the two years surveyed. 4.
      Balance score and Dietary habits score decreased during the two years along with
      the increase in subjective symptoms. The survey suggests that better dietary
      habits and lifestyle are necessary in order to maintain good physical condition
      in junior high school students.

PMID- 10067078
TI  - [Role of school lunch in primary school education: a trial analysis of school
      teachers' views using an open-ended questionnaire].
AB  - We tried to analyze synthetically teachers' view points associated with health
      education and roles of school lunch in primary education. For this purpose, a
      survey using an open-ended questionnaire consisting of eight items relating to
      health education in the school curriculum was carried out in 100 teachers of ten
      public primary schools. Subjects were asked to describe their view regarding the
      following eight items: 1) health and physical guidance education, 2) school lunch
      guidance education, 3) pupils' attitude toward their own health and nutrition, 4)
      health education, 5) role of school lunch in education, 6) future subjects of
      health education, 7) class room lesson related to school lunch, 8) guidance in
      case of pupil with unbalanced dieting and food avoidance. Subjects described
      their own opinions on an open-ended questionnaire response sheet. Keywords in
      individual descriptions were selected, rearranged and classified into categories
      according to their own meanings, and each of the selected keywords were used as
      the dummy variable. To assess individual opinions synthetically, a principal
      component analysis was then applied to the variables collected through the
      teachers' descriptions, and four factors were extracted. The results were as
      follows. 1) Four factors obtained from the repeated principal component analysis
      were summarized as; roles of health education and school lunch program (the first
      principal component), cooperation with nurse-teachers and those in charge of
      lunch service (the second principal component), time allocation for health
      education in home-room activity and lunch time (the third principal component)
      and contents of health education and school lunch guidance and their future plan
      (the fourth principal component). 2) Teachers regarded the role of school lunch
      in primary education as providing daily supply of nutrients, teaching of table
      manners and building up friendships with classmates, health education and food
      and nutrition education, and developing food preferences through eating lunch
      together with classmates. 3) Significant positive correlation was observed
      between "the teachers' opinion about the role of school lunch of providing
      opportunity to learn good behavior for food preferences through eating lunch
      together with classmates" and the first principal component "roles of health
      education and school lunch program" (r = 0.39, p < 0.01). The variable "the role
      of school lunch is health education and food and nutrition education" showed
      positive correlation with the principle component "cooperation with nurse
      teachers and those in charge of lunch service" (r = 0.27, p < 0.01). Interesting
      relationships obtained were that teachers with longer educational experience
      tended to place importance in health education and food and nutrition education
      as the role of school lunch, and that male teachers regarded the roles of school
      lunch more importantly for future education in primary education than female
      teachers did.

PMID- 10067079
TI  - [Reproducibility and validity of a semi-quantitative food frequency
      questionnaire].
AB  - The reproducibility and relative validity of a semi-quantitative food frequency
      questionnaire (FFQ) were evaluated. Subjects were 72 (36 men and 36 women)
      residents of N island, Shimane Prefecture in Japan, aged 50-76 years. The
      questionnaire was administered twice at an interval of one week (FFQ1, FFQ2), and
      7-day weighing diet records were collected during that period. This protocol was
      conducted in summer and winter. The mean intakes for 11 nutrients calculated from
      the FFQ1 and FFQ2 were similar and, those from the FFQ1 were smaller than those
      from the diet records for all but fat and vitamin C. Pearson correlation
      coefficients assessing reproducibility between nutrient intakes from FFQ1 and
      FFQ2 ranged from 0.59 for vitamin C to 0.90 for carbohydrate. Validity was
      measured by comparing nutrient intakes from FFQ1 with those from the 7-day diet
      record, and Pearson correlation coefficients ranged from 0.15 for iron to more
      than 0.35 for total energy and macronutrients. These correlation coefficients
      showed slight difference by gender or age group, but did not vary materially
      between seasons. These data indicate that this questionnaire is reproducible but
      has some problems in validity.

PMID- 10067080
TI  - [The number of beds needed for patients with infectious diseases that require
      hospitalization by law].
AB  - PURPOSE: Using a statistical model, a study was conducted on the number of beds
      that are needed for patients with infectious diseases who are required by law to
      be hospitalized. METHODS: Based on 1995 data, the incidence of such infectious
      diseases and the average duration of isolation of these patients in Japan were
      obtained. Using a Poisson distribution, the probability that the number of
      patients that exceeds a specific number over an average duration of
      hospitalization was computed in a finite population. The observation period was
      then extended to one year and the probability that the number of patients did not
      exceed a specific number during one year was calculated. RESULTS: In 1995, the
      annual incidence of infectious diseases requiring isolation by hospitalization
      was 1.38 per 100,000 population and the average duration of hospital confinement
      was 13.8 days. The estimated patient numbers calculated based on the probability
      of less than 0.001 that the number of patients would not exceed a specific number
      were: 2 for 30,000 population, 3 for 50,000 through 100,000, 5 for 200,000 and
      300,000, 5 for 400,000 and 500,000, 6 for 750,000 and 1,000,000, 8 for 2,000,000,
      and 10 for 3,000,000. CONCLUSION: By using a Poisson distribution, a method was
      developed for estimating the number of beds that are needed for patients with
      infectious diseases when hospitalization was mandatory.

PMID- 10067081
TI  - [Investigation on daily life concerning patients with spinocerebellar
      degeneration].
AB  - Patients with spinocerebellar degeneration show gradual progression of symptoms
      and decreasing ADL (activities of daily living), resulting in their having many
      problems concerning daily care. However, there are relatively few patients with
      such diseases who have participated in those education and consultation services
      provided by the public health center. To better meet the needs of these patients,
      we investigated their attitudes and the various parameters affecting their actual
      daily life. A survey of patients in Sakai-city was conducted via a questionnaire
      mailed to 100 patients who applied for financial aid for spinocerebellar
      degeneration in 1996. A total of 74% of the patients responded to the
      questionnaire. Patients over 50 years old accounted for 77% of the total, Among
      all responding patients, 14% had their own occupation. The average period of
      morbidity was 4.8 years. Most (62%) patients were being treated as outpatients.
      Main symptoms of the patients were associated with speech and trunk movement.
      About one-fourth of the patients required constant assistance for bathing and
      transportation. The main person providing care for the patients was the spouse.
      Main demands for health and welfare services were, "consulting on care and daily
      life", and "the opportunity for patients to talk with each other." The need for
      health services is high because such patients have several symptoms. Information
      acquired through this investigation from patients and their families will be
      useful for providing better care for patients, with spinocerebellar degeneration.

PMID- 10067082
TI  - [Effectiveness of day care service for elderly patients with dementia and their
      caregivers as observed by comparison of days with and without day care services].
AB  - PURPOSE: To explore the effectiveness of day care service for the dementia
      elderly and their caregivers. METHODS: Subjects were sixty caregivers who took
      care of dementia elderly and were using day care service in two municipalities.
      The data on caregiving, care burden of caregivers, and time schedule of daily
      life were obtained from a questionnaire that was distributed at the five day care
      centers and collected through home visits. The data from a day with day care were
      compared with data from a day without. RESULTS & DISCUSSION: 1. Caregivers
      reported that their care burden was reduced on the day with day care, even though
      their time schedule for the day was not so different from the day without day
      care. 2. The harder the caregiving became, the more caregivers felt relieved on
      the day with day care. 3. Obviously, day care would no be expected to have the
      same effect in situations in which the caregiver is elderly or works outside the
      home all day. CONCLUSION: When we think about day care it is important to provide
      a well adapted home care program which effectively meets the needs of the
      dementia elderly and their caregivers.

PMID- 10067083
TI  - [Lifestyle, mental health, and awareness of health among Japanese bus drivers].
AB  - To examine lifestyle, mental health and awareness of health, a self-administered
      questionnaire survey was performed among 751 employees of a bus company in a
      rural city of Japan. From 597 (79.5%) respondents, we analyzed 130 male bus
      drivers and age-matched 130 male clerks. The questionnaire included eleven
      questions about lifestyle and mental health, three questions about awareness of
      health, and questions on personal concern about specific parts of the body or
      diseases, and health information they needed. Answers for lifestyle and mental
      health were classified into the categories of "good" or "not good" practices
      recommended by Breslow and Morimoto. The results were as follows; 1) Over 80
      percent of subjects of both groups had good awareness of health, but bus drivers
      had significantly worse lifestyle with regard to nutritional intake (p < 0.05),
      daily walking (p < 0.001), sports (p < 0.05), and sleeping hours (p < 0.001). 2)
      Bus drivers had significantly greater prevalence of concern about their
      cardiovascular system, esophagus and gastrointestinal system, and joints and
      bones than clerks (p < 0.05). 3) Bus drivers had a significantly greater need for
      information about nutritional intake (p < 0.001), and methods for prevention of
      diseases (p < 0.01). From these results, the discrepancy between awareness of
      health and lifestyle seen in this study, especially in food intake, walking time,
      sports participation, and sleep, may have resulted from the bus driver's
      characteristics of job, for example, long and irregular working hours. Therefore,
      effective guidance on health and lifestyle changes to restore balance and improve
      their lifestyle.

PMID- 10067084
TI  - [Conversion syndromes in neurology. A psychopathological and psychodynamic
      differentiation of conversion disorder, somatization disorder and factitious
      disorder].
AB  - Conversion syndromes are frequent among medically unexplained somatic symptoms in
      neurology. A careful differential diagnosis must be carried out in a psychiatric
      consultation service. In a prospective study lasting for over four years 169
      patients with pseudoneurological signs of conversion were included. From a
      clinical point of view the following conversion syndromes were presented:
      astasia/abasia: 27.2%, paresis/plegia: 24.3%, aphonia: 1.8%, hyp-/anaesthesia:
      21.9%, blindness: 5.3%, non-epileptic seizures: 19.5%. According to the
      diagnostic criteria of DSM-III-R three subgroups were differentiated: conversion
      disorder (n = 132), somatisation disorder (n = 28), factitious disorder (n = 9).
      Intermittent courses of illness were prevailing in conversion disorder, whereas
      chronic courses predominated in the other two subgroups. High rates of
      psychiatric comorbidity were typical signs of somatisation disorder. Frequent
      autodestructive motives (suicidality, deliberate and covert self-harm, chronic
      pain, high rate of operations) in illness behaviour had to be registered in
      somatisation and factitious disorder. Both subgroups were characterised by
      frequent traumatic events during early development. Important socio-economic
      aspects of illness behaviour above all in somatisation and factitious disorder
      were underlined. The results are discussed in terms of psychiatric differential
      diagnosis and psychiatric comorbidity, psychodynamic evaluation, illness
      behaviour and therapeutic options in a C/L-service.

PMID- 10067085
TI  - [Contribution of the clinical psychologists to rehabilitation of children with
      craniofacial abnormalities].
AB  - This paper describes the role of the clinical psychologist collaborating in an
      interdisciplinary rehabilitation team for children with severe congenital
      craniofacial disorders. This includes: 1. Psychological counseling during the
      initial period of responding to the traumatic experience of the child's birth; 2.
      Preparing the child and parents for surgery and hospitalisation; 3. Developmental
      assessment and counseling in parenting and educational issues; 4. Prevention of
      social-emotional disorders and psychological support for the long-term adjustment
      to facial difference.

PMID- 10067086
TI  - [Comparison of the body image of healthy and psychiatrically and chronically ill
      children using the KBMT-K].
AB  - Initially some results from empirical studies regarding body satisfaction and
      differentiation of body experience of children are described. METHOD: In our
      study several groups of children showing different kinds of illness at the age of
      eight to twelve years were subjected to the "Korperbildmaltest fur Kinder" (KBMT
      K, Gunter) (Colour-A-Person-Dissatisfaction-Test for Children), a depression
      inventory and an anxiety test. Furthermore we examined the children's body
      knowledge. We assessed two samples of children in psychiatric and
      psychotherapeutic inpatient treatment. The diagnoses were disruptive behaviour (n
      = 32) or emotional disturbances (n = 36). Three other groups were formed of
      children with somatic chronic illnesses (asthmatics (n = 47), inpatient diabetics
      (n = 34) and outpatient diabetics (n = 30)). We compared the test scores with
      those of healthy children. RESULTS: Only the younger (eight to ten years old)
      children of both samples showed a significantly lower body satisfaction in
      comparison to healthy children, the young girls with a chronic somatic illness
      having the lowest scores. Older girls with a chronic somatic illness (aged 11 or
      12 years) had a significantly poorer differentiation of their body experience
      than the healthy peers, a finding we had not expected in advance. Comparing the
      different clinical samples with the healthy sample, only the emotionally
      disturbed children were significantly more dissatisfied with their own body.
      Whereas we were able to demonstrate by statistical analyses that in addition to
      the illness, depression and anxiety had an impact on body image, the knowledge of
      the body did not influence the above-mentioned concepts. The results are
      discussed.

PMID- 10067087
TI  - [Effect of subjective theories on the coping with illness process--exemplified by
      patients with chronic pancreatitis].
AB  - The concept of locus of control, as a basic aspect of subjective self-perception
      and world perception, has turned out to be an important construct in the area of
      psychosomatic medicine for the explanation and prediction of illness-relevant
      behaviour. This study investigates the influence of illness-specific locus of
      control on the course of the disease in patients suffering from chronic
      pancreatitis. While most investigations in this area of research are
      methodologically restricted to paper-and-pencil questionnaires, the present study
      registered the concept of locus of control within the metatheoretical framework
      of "research programme subjective theories". This programme focuses on the
      capacity of patients to create their own models of their relationship with the
      world. The procedure involves two stages of research: In the first phase of
      communicative validation the patient is interviewed about the possibility to
      influence the course of his disease. A few days later, in a second session, the
      patient models together with the interviewer a structure of his subjective
      theory. In the second stage, the phase of explanatory validation, this model will
      be tested using empirical methods for validation. Compared to a paper-and-pencil
      questionnaire this procedure means more expenditure for research. On the other
      hand the results are detailed and specified. Hence, it can be shown that patients
      dispose over a set of subjective theories on how to influence the course of their
      illness. These subjective theories determine the patients' coping styles.
      Methodological and theoretical consequences for coping research and treatment of
      chronic diseases are discussed.

PMID- 10067088
TI  - 5th Annual Conference of the International Society for Quality of Life Research.
      Baltimore, Maryland, USA. 15-17 November 1998. Abstracts.

PMID- 10067089
TI  - [Clinical outcomes in low grade follicular lymphoma].
AB  - Twenty-six patients with follicular small-cleaved lymphoma (FSCL) and 16 patients
      with follicular mixed lymphoma (FML) were treated at the Nichidai Itabashi
      Hospital between 1981 and 1995. The 5-year overall survival rate was 74.3% and
      70.0% for the FSCL and FML patients, respectively. Of the patients with stage III
      IV FSCL, 9 were assigned to a "watchful waiting" follow-up course and 13 were
      treated with a single alkylating agent or CHOP therapy. The 5-year failure-free
      survival rate was 66.7% and 33.0%, respectively. Of the patients with stage II-IV
      FML, 6 were treated with CHOP or MACOP-B protocol. The complete response rate for
      this group was only 33.3%, and none of the patients were in remission for more
      than 2 years. Histological transformation into diffuse aggressive lymphoma was
      observed in 7 patients, with the median time from diagnosis to transformation at
      50 months. Three of those patients were successfully treated with intensive
      chemotherapy after transformation.

PMID- 10067090
TI  - [New quinolone versus vancomycin/tobramycin for intestinal sterilization in
      patients who undergo allogeneic bone marrow transplantation].
AB  - The frequency of infection in recipients of allogeneic bone marrow transplants
      (BMT) who received oral new quinolones (NQ) was compared with that in BMT
      recipients who were given oral vancomycin/tobramycin (V/T). Between 1984 and
      1997, our hospital treated 79 patients with V/T and 90 patients with NQ. Number
      of febrile days, duration of intravenous antibiotics administration, and
      frequency of documented infections were statistically the same for both groups.
      However, the frequency of grampositive bacterial infections, especially
      staphylococcal infections, was slightly higher in patients receiving NQ than in
      patients receiving V/T (p = 0.12). Of the patients who received NQ, those who
      underwent unrelated donor BMT procedures were generally febrile for slightly
      longer periods than those who underwent related donor BMT procedures (p = 0.10).
      These results suggest that oral NQ is as effective as oral V/T for the prevention
      of serious gramnegative bacterial infections in patients who undergo BMTs.

PMID- 10067091
TI  - [A trial for peripheral blood stem cell harvest by combination of G-CSF with ABVD
      regimen in the management of Hodgkin's disease].
AB  - We studied the possibility of performing peripheral blood stem cell (PBSC)
      harvests during the course of ABVD therapy by adding G-CSF to the treatment
      regimen. Six patients with high-risk Hodgkin's disease (HD) (5 untreated cases
      with bulky mass and 1 relapsed case) received G-CSF (5 micrograms/kg)
      subcutaneously from day 8 to day 13 of their first course of ABVD treatment; the
      numbers of CD34+ cells and CFU-GM were monitored. PBSC harvests were performed on
      day 12 and day 13 of subsequent ABVD plus G-CSF treatment courses. For all
      patients tested, we were able to harvest CFU-GM (3.78 +/- 1.19 x 10(5)
      colonies/kg) for peripheral blood stem cell transplants (PBSCT) by performing 2
      to 4 cycles. of apheresis, without any modification to the original ABVD
      protocol. These findings suggest that ABVD plus G-CSF therapy is a strong
      candidate for the treatment of patients with high-risk HD who may undergo
      autologous PBSCT.

PMID- 10067092
TI  - [A case of aggressive myeloma with abnormal plasmocytes in pleural effusion and
      cerebrospinal fluid].
AB  - Extramedullary involvement of myelomas is common but invasion of myeloma cells
      into the pleural cavity and cerebrospinal fluid (CSF) is rare. We report an
      aggressive case of multiple myelomas (Bence Jones lambda type) with pleural and
      meningeal infiltration. A 66-year-old man was referred to our hospital because of
      anemia, thrombocytopenia, and dyspnea. His peripheral blood contained 2% bizarre
      plasma cells. Bone marrow biopsy specimens and immunoelectrophoresis confirmed
      the diagnosis. A chest radiograph disclosed pleural effusion in both lungs
      containing M-protein and numerous abnormal cells. The patient also suffered from
      disorientation, speech disorder, and muscle weakness. A lumbar puncture revealed
      atypical plasma cells in CSF. Four courses of chemotherapy (cyclophosphamide,
      doxorubicin, and prednisolone) and the intrathecal administration of methotrexate
      and cytarabine at 3-week intervals were effective in decreasing the pleural
      effusions and eliminating plasma cells from CSF. Nonetheless a chest wall tumor,
      pelvic mass, and pneumonia developed, and the patient died 5 months after initial
      presentation. Pleural infiltration of myeloma cells and multiple lesions with
      plasma cell involvement were discovered at autopsy.

PMID- 10067093
TI  - [Allogeneic peripheral blood stem cell transplantation in an elderly patient with
      myelodysplatic syndrome with myelofibrosis].
AB  - Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has in recent
      years become an alternative to allogeneic bone marrow transplantation because it
      facilitates rapid hematopoietic reconstitution without an increase in the
      incidence of severe graft-versus-host disease (GVHD). We report on a 61-year-old
      man with myelodysplastic syndrome (MDS) and myelofibrosis who received an allo
      PBSCT from his HLA-matched 68-year-old brother. The preparative regimen consisted
      of busulfan and cyclophosphamide. Cyclosporin A and methotrexate were
      administered for GVHD prophylaxis. The donor was treated with granulocyte colony
      stimulating factor (G-CSF) at a dose of 10 micrograms/kg/day subcutaneously for 4
      consecutive days. A preparation of 4.04 x 10(6) CD34+ cells/kg recipient weight
      was collected in a single apheresis and infused immediately. Engraftment times to
      a neutrophil count greater than 500/microliter and platelet count greater than
      2.0 x 10(4)/microliter were 15 days each. Acute GVHD of grade II developed, but
      was resolved with methylprednisolone. However, the patient died of thrombotic
      microangiopathy 97 days after his allo-PBSCT. Administration of G-CSF and
      apheresis in the donor were feasible and well tolerated. Allo-PBSCT may result in
      earlier engraftment and be especially beneficial to elderly patients with MDS.

PMID- 10067094
TI  - [Myelodysplastic syndrome accompanied by i(17) (q10) anomaly following pure red
      cell aplasia and transient myeloproliferative stage].
AB  - A 71-year-old man was given a diagnosis of pure red cell aplasia (PRCA) in May
      1995. However, immunosuppressive agents, including prednisolone, azathioprine,
      and cyclosporin A, were not effective, and he required frequent red cell
      transfusions. In September 1995, leukocytosis and thrombocytosis developed
      (peaking at 10,100/microliter white cells and 98.1 x 10(4)/microliter platelets,
      respectively, in November 1996). Conversely, the patient's peripheral blood count
      began to decrease in July 1996, and pancytopenia progressed thereafter i(17)
      (q10) chromosomal abnormality of bone marrow cells was detected in November 1996.
      The patient was readmitted due to the progression of thrombocytopenia (1.2 x
      10(4)/microliter). His bone marrow has 16.6% blasts, and a diagnosis of
      myelodysplastic syndrome (MDS) was made. The patient died in November 1997. His
      hematological state demonstrated significant changes in a relatively short period
      and severe hypoerythropoiesis and eosinophilia of the bone marrow persisted
      throughout the clinical course. These findings suggested that a common deranged
      stem cell was the origin of 3 different states; PRCA, chromic myeloproliferative
      disorder, and MDS. The i(17) (q10) anomaly may have caused the acute
      proliferation of blasts and pancytopenia.

PMID- 10067095
TI  - [Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia
      after allogeneic bone marrow transplantation: analysis of natural killer cell
      activity and T-cell receptor repertoire in bone marrow T cells that exhibited
      graft-versus-leukemia activity].
AB  - Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255
      days after allogeneic bone marrow transplantation. The patient received a donor
      lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved
      complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR
      state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD)
      was observed. Natural killer (NK) cell activity was elevated. Also, analysis of
      the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells
      of the TCR V beta and J beta subfamilies. These observations provide evidence for
      the clonal expansion of allogeneic T cells that are capable of mediating
      antileukemic activity without causing GVHD.

PMID- 10067096
TI  - [Successful lithium carbonate therapy for a patient with intractable and severe
      aplastic anemia].
AB  - A 16-year-old female patient who had been given a diagnosis of severe aplastic
      anemia underwent 2 courses of a combined regimen of corticosteroid pulse therapy
      and androgen therapy. This proved ineffective. Antilymphocyte globulin therapy
      was also ineffective. The patient was then given lithium carbonate at a dose of
      600 mg/day in combination with an androgen derivative. This had a dramatic effect
      on her peripheral blood smear. Within 3 weeks after the first course of this
      treatment, she no longer required red blood cell transfusions. Also, once the
      lithium carbonate dose was increased to 1,200 mg/day, the patient no longer
      needed exogenous platelet transfusions. Approximately 6 months after the start of
      combination therapy, a peripheral blood smear showed entirely normal results.
      However, 2 months after lithium carbonate was discontinued probably as a result
      of drug-induced liver dysfunction, both leukocytopenia and thrombocytopenia
      reappeared. Therefore, lithium carbonate was readministered at a dose of 400
      mg/day, and later at a dose of 800 mg/day. Again, the patient showed improvements
      in 3 blood components without any adverse effects. We concluded that lithium
      therapy was remarkably useful for this patient with intractable and severe
      aplastic anemia.

PMID- 10067097
TI  - [Adult T-cell leukemia with elevated serum hyaluronic acid levels paralleling
      disease activity].
AB  - We report on two adult T-cell leukemia (ATL) patients whose levels of serum
      hyaluronic acid (HA) moved in parallel with the clinical activity of their
      disease. A 66-year-old man was admitted to our hospital because of
      unconsciousness and hypotension. Acute type ATL complicated by hypercalcemia and
      myelofibrosis was diagnosed. Before therapy, the level of patient's serum HA was
      2,045 to 4,010 ng/ml (normal range: 50 >). After he achieved complete remission
      (CR) through chemotherapy, his serum HA was 36 ng/ml. Several months later,
      however, his ATL relapsed, and his serum HA increased to 393 ng/ml. The other
      patient was an 80-year-old man who had been admitted on the suspected diagnosis
      of ATL. Before chemotherapy, his serum HA was high (3,420 ng/ml). After CHOP
      therapy, he entered CR and his HA decreased to 122 ng/ml. He remains in CR with
      slightly elevated levels of HA (127 to 212 ng/ml), and is being followed up on an
      out-patient basis.

PMID- 10067098
TI  - [Adverse reactions to autologous peripheral blood stem cell transplantation in
      patients over 65 years old].
AB  - We compared the outcomes of autologous peripheral blood stem cell transplantation
      (auto-PBSCT) for two groups: one composed of 6 patients over 65 years of age, and
      the other, of 8 younger patients. Transfused CD34-positive cells and CFU-GM
      counts, days to achieve a neutrophil count of over 500/microliter after
      transplantation, days to achieve a platelet count of over 50,000/microliter, and
      blood transfusion times were similar in both groups. Organ toxicity also appeared
      similar in both groups, but no severe adverse reactions (WHO grade/4) were
      observed. Poor performance status due to advanced tumors improved in some
      patients after PBSCT. We concluded that PBSCT is tolerable in patients over 65
      years of age and useful as salvage therapy.

PMID- 10067099
TI  - [Rapid recovery of hemopoiesis and alleviation of symptoms similar to peri
      engraftment syndrome after donor leukocyte infusion].
AB  - A 28-year-old man who had received an allogeneic bone marrow transplant 7 years
      earlier experienced a relapse of chronic myelogenous leukemia in an accelerated
      phase. He was unsuccessfully treated with vincristine (VCR) and interferon-alpha
      (IFN-alpha), and subsequently received a donor leukocyte transfusion (CD3+ cells:
      1.5 x 10(7)/kg). Rapid hematologic recovery was observed and a complete remission
      was obtained without graft-versus-host disease (GVHD) or bone marrow aplasia. It
      may be that the preceding regimen of chemotherapy (VCR + IFN-alpha) contributed
      to the patient's recovery by reducing the tumor burden.

PMID- 10067100
TI  - [Fungi in the intestine. Clinical significance].

PMID- 10067101
TI  - [How to proceed? ERCP in acute pancreatitis?].

PMID- 10067102
TI  - [How to proceed? ERCP in acute pancreatitis?].
AB  - The standard treatment of acute pancreatitis is primarily supportive, including a
      well standardized conservative therapy and additionally specific interventions in
      complicated disease. The role of early endoscopic retrograde
      cholangiopancreatography in acute pancreatitis has been discussed for about 20
      years. The etiology of pancreatitis plays an important role in making the
      decision for early interventional treatment. The results of clinical trials about
      early interventional treatment of acute biliary pancreatitis demonstrate that the
      outcome of patients without signs of biliary stone impaction or acute cholangitis
      is burdened by more severe complications than in patients treated conservatively.
      Urgent endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy
      and stone extraction within 72 hours of admission reduces the frequency of major
      complications only in patients with acute biliary pancreatitis with obstructive
      jaundice or biliary sepsis.

PMID- 10067103
TI  - [State of the art: gastroenterologic surgery].
AB  - Microcirculation and molecular biology are the hottest topics in modern surgical
      research. In familial adenomatous polyposis the incidence of carcinoma can be
      assessed by the localisation of the PAC-gene mutation. Restorative
      proctocolectomy with ileoanal pouch represents the procedure of choice. The
      optimal age for the operation varies between 20 and 35 years according to the
      localisation of the mutation. RT-PCR directed to recently defined surface
      antigens allows for the sensitive detection of intraoperative tumor cell
      liberation. Due to tumor cell detection in the systemic circulation the
      perioperative administration of monoclonal antibodies must be advocated. A
      preciser definition of lymphogenic tumor spread underlines the importance of
      systematic lymphadenectomy in resection of the colon. The understanding of
      microcirculatory disorders has optimized surgical decision-making intra- and
      perioperatively: function of renal and hepatic microcirculation is a reliable
      parameter to predict graft quality already intraoperatively and to monitor
      therapeutic approaches to ischemia/reperfusion injury. Results in the therapy of
      acute pancreatitis could be improved by operating less and later. Analysis of
      pancreatic microcirculation resulted in an improvement of ICU-therapy in the
      early stages of the disease. Transplantation of the liver is limited to
      hepatocellular carcinoma when its localisation or the residual hepatic function
      after resection preclude curative excision. In addition liver transplantation
      should not be carried out in tumors larger than 5 cm or in patients with more
      than 3 tumor nodules. Liver resection for colorectal metastases is a standard
      procedure. A second resection of recurrent metastases is advocated since an
      identical median survival can be achieved compared to the primary resection (32
      mo). The surgical treatment of non-colorectal liver metastases is under
      evaluation and should be restricted to oncological centers. Special aspects of
      backwashileitis in ulcerative colitis will be outlined concerning timing of
      colectomy, pouch construction, and follow-up.

PMID- 10067104
TI  - [Acute lower abdominal pain in constipation].

PMID- 10067105
TI  - [Stage IIIa multiple myeloma].

PMID- 10067106
TI  - [Current status of positron emission tomography in diagnosis of abdominal
      tumors].
AB  - PET is recognized as a powerful imaging research tool. Based on
      pathophysiological and biochemical principles, functional PET imaging allows to
      assess parameters of tumor biology not easily accessible to conventional imaging
      such as metabolic activity, proliferation, adrenergic transmitter uptake or
      accumulation of cytostatic drugs in individual tumor manifestations. This article
      reviews recent developments of PET imaging with 2-[F-18]fluoro-deoxyglucose (FDG)
      in the Diagnosis of abdominal malignant tumors. Diagnosis of pancreatic carcinoma
      and its liver metastases, locoregional and distant recurrence as well as therapy
      control of colorectal cancer, nodal and extranodal staging and therapy monitoring
      of malignant lymphoma can be reliably achieved with PET. Encouraging clinical
      results and attractive new imaging concepts promise increasing use and importance
      of PET for imaging abdominal malignancies.

PMID- 10067107
TI  - [Possibilities of virtual gastrointestinal endoscopy].
AB  - Beside the technological development of the modalities, secondary image
      reconstruction procedures are of increasing interest for diagnostic purposes and
      preoperative planning. Recently the simulation of endoscopic views--so called
      virtual endoscopy--has become available for presenting volume datasets. This new
      technique, usually based on CT and MRT data-sets, leads to new possibilities for
      examination of gastrointestinal organs and vasculature. Most interest has
      focussed on colon examinations, depending on a detailed knowledge of the
      technical procedure of the examination and additional experience of endoscopic
      techniques of the examiner. The procedures for the different parts of the
      gastrointestinal tract are explained.

PMID- 10067108
TI  - [New perspectives in 3D MR colonography].
AB  - Filling the colon lumen with contrast allows for 3D-MR-colonography. The 3D data
      set can be postprocessed to multiplanar reconstruction, surface shaded displays
      as well as virtual colonoscopy. The latter facilitates the differentiation
      between haustra and polyps and enables detection of polyps down to 6 mm in size.
      Multiplanar reconstructions provide the assessment of the inner wall contour. The
      morphology of the colonic wall itself can be assessed on T1- or T2-weighted
      images. T1-weighted sequences performed before and after i.v. contrast
      administration and T2-weighted sequences depict pathologies based on their
      contrast uptake respectively on their tissue water content. This concept of
      colonic imaging practicable in less than 15 minutes is useful for the assessment
      of inflammatory disease, for polyp detection as well as for tumour staging.

PMID- 10067109
TI  - [Stent therapy].
AB  - Expandable metal stents are a significant advance in the treatment of malignant
      gastrointestinal tract obstruction. The devices available are not perfect in
      design and need further technical improvement. However they already offer
      advantages over conventional plastic stents. They are becoming standard for
      esophageal stenting. Indications for metal stents in other locations of the
      gastrointestinal tract have to be evaluated. Endoscopic stenting is now the
      method of choice in the palliative treatment of jaundice in patients with
      inoperable biliopancreatic neoplasias. Stent clogging as a result of biliary
      sludge and biofilm remains an unsolved problem of plastic stents. Expandable
      metal stents remain patent longer but are reserved for patients with good general
      health.

PMID- 10067110
TI  - [Endoscopy 2000].
AB  - The trends and developments in endoscopy of the coming years are many-sided.
      Improved fiber-optics and invention of computer technology lead to smaller
      endoscopes with higher resolution. Electronic image processing makes three
      dimensional measurement or presentation of objects possible. In endosonography a
      trend to miniaturization is also obvious. Advances in molecular biology and
      imaging procedures will strengthen the importance of endoscopy in the future.
      Moreover a differentiated use of new laser technologies will improve the
      possibilities of endoscopic diagnosis and therapy. The use of electronic
      diagnostic documentation systems will contribute to a standardized nomenclature
      and to a quality-improvement of documentation in the near future. The utilization
      of modern electronic communication systems will facilitate intra- and
      interdisciplinary exchange of information.

PMID- 10067111
TI  - [Comparison of invasive and drug therapy approaches in non-transmural acute
      infarct].

PMID- 10067112
TI  - [Diagnosis and therapy of lymph node tuberculosis].
AB  - Due to an increase of lymph node tuberculosis and associated diagnostic problems
      the question for the easiest and most accurate diagnostic measures was asked.
      Furthermore, the success of surgical and pharmacologic treatment was evaluated. A
      total of 16 patients (nine females, seven males) treated at the medical
      outpatient clinic between 1977 and 1995 because of lymph node tuberculosis were
      evaluated retrospectively. Diagnosis had been established in all cases either by
      fine needle aspiration or surgical excision. The mean age was 31 years (range 17
      68). In 10 patients cervical lymphomas were found. Other localisations were
      supraclavicular, inguinal, axillary and mediastinal. In 94% of the patients a
      fine needle aspiration was performed to ascertain diagnosis. Acid-fast bacilli
      were found in 36% and mycobacteria were cultured in 92%. Five patients (31%) had
      a surgical excision with acid-fast bacilli in two and positive cultures from all
      specimens. All patients had chemotherapy, in most cases started by a combination
      of three and followed by a combination of two drugs. According to our results a
      fine needle aspiration is justified as a first diagnostic step if lymph node
      tuberculosis is suspected. A positive result can be regarded as conclusive and
      spares surgical intervention. Since negative results do not exclude tuberculosis
      they justify surgical excision for final diagnosis.

PMID- 10067113
TI  - [Brief history of recent hemp cultivation in Switzerland and subsequent medico
      legal problems resulting from hemp cultivation].
AB  - In March 1995, a decision about cultivation of cannabis was issued by the Swiss
      Federal Offices of Public Health, Police and Agriculture in order to satisfy the
      growing interest of farmers and other people in hemp farming. It pointed out that
      1)... each hemp plant contains THC and must be therefore considered a drug, 2)...
      no permission is required for those who grow hemp without the intention to
      produce drugs ... meaning that the choice of the plant variety was not restricted
      to those which are characterized by a low THC concentration and grown in a few
      countries belonging to the European Union. Claiming that natural hemp must
      contain significant amounts of THC and thanks to the Swiss legislation, areas
      dedicated to hemp cultivation develop considerably. Most hemp plants which are
      submitted to our laboratories by the police for THC quantification belong to the
      drug-type. Nowadays, a great deal of goods (food and beverages, cosmetics, drugs)
      made of hemp are marketed in Switzerland. Strong suspicions exist however that
      several of these products could be used as a screen for the illegal market of
      cannabis. For instance, despite financial support from the state, fiber hemp
      cultivation remains unsuccessful. No advantage with regard to seed productivity,
      edible seed and essential oils qualities and yields have been found for drug hemp
      over fiber hemp by agricultural research stations up to now. Several clues about
      the possible illicit use of hemp goods rich in THC, especially hemp tea made of
      flower tops and "therapeutic" pillows filled with cannabis exist. Recently, two
      Federal edits were issued in order to restrict the selling of hemp seedlings and
      of hemp foods and beverages to those containing only low amounts of THC. However,
      the marketing of hemp plants used for decorating remains free partly explaining
      the recent success of these "beautiful" plants. Broadly speaking, the Swiss and
      European legislations about hemp have approached mutually during the last years.

PMID- 10067114
TI  - [Is there a standard therapy in advanced ovarian carcinoma?].

PMID- 10067115
TI  - [Cocaine: its possible role in coronary arteriosclerosis and myocardial infarct.
      Case reports and review of the literature].
AB  - Cocaine is a frequently used drug with many known effects on the cardiovascular
      system. It leads also to structural changes of the coronary arteries that can
      result in severe chest pain or even acute myocardial infarction. We discuss two
      patients with infarction, differentiate between chest pain and infarction and
      suggest some important therapeutic measures.

PMID- 10067116
TI  - [Fatigue, diffuse alopecia, Hashimoto thyroiditis].

PMID- 10067117
TI  - [Chronic bacterial prostatitis].

PMID- 10067119
TI  - [Phosphatidylserine metabolism and biosynthetic regulation in mammalian cells].

PMID- 10067120
TI  - [Biochemistry of pain].

PMID- 10067121
TI  - [F1-ATPase; the stepping rotary motor in ATP synthase].

PMID- 10067122
TI  - [Novel F-actin-binding proteins involved in cell-cell adhesion].

PMID- 10067123
TI  - [Fukutin, a novel protein product responsible for Fukuyama-type congenital
      muscular dystrophy].

PMID- 10067124
TI  - [Isoform multiplicity of microphthalmia-associated transcription factor].

PMID- 10067125
TI  - [Cloning of disease genes by chromosome mapping].

PMID- 10067126
TI  - [Recent progress on the study of structural zinc].

PMID- 10067127
TI  - [Hypertension is a frequent illness].

PMID- 10067128
TI  - [Molecular genetics of hypertension in the human].
AB  - In the general population blood pressure varies along a continuum and is
      regulated via multiple mechanisms involving many genetic loci and environmental
      factors. Epidemiological studies suggest that blood pressure variance is
      attributable to both genetic factors and environmental factors to the same
      magnitude. The molecular basis for three forms of sever hypertension transmitted
      on an autosomal basis has been recently elucidated: a) the glucocorticoid
      suppressible aldosteronism (GSA), b) the Liddle's syndrome and c) the syndrome of
      apparent mineralocorticoid excess (AME). GSA is due to expression of a chimeric
      gene produced by fusion of the 11 beta-hydroxylase promoter with the region
      encoding the enzyme aldosterone-synthase. Expression of this chimeric gene occurs
      in the zona fasciculata of the adrenal cortex, under the control of ACTH, and can
      be suppressed by administration of glucocorticoids. Liddle's syndrome is due to
      mutations in the beta or gamma chain of the epithelial sodium channel in distal
      renal tubule cells. The hyperactivity of this channel caused by the mutations
      results in increased sodium reabsorption, which can be suppressed by
      administration of amiloride or triamterene. AME is caused by mutations of the 11
      beta-hydroxysteroid dehydrogenase type 2 enzyme, an enzyme that metabolises
      cortisol into its receptor inactive keto-form cortisone, thus protecting the
      mineralocorticoid receptor from occupation by glucocorticoids. Apart from these
      rare genetic defects of the extended renin-angiotensin system, there are many
      susceptibility genes that might increase the risk of hypertension in a given
      environment. Several studies have demonstrated a link between the angiotensinogen
      gene and familial hypertension. One variant of angiotensinogen gene is associated
      with elevated plasma angiotensinogen levels and is more prevalent among
      hypertensive than among normotensive. This observation shows the relationship
      between the angiotensinogen genotype, the intermediate phenotype (i.e., plasma
      angiotensinogen elevation), and the distant phenotype (i.e., blood pressure
      elevation). The identification of these genes as well as other informative
      genetic markers distributed along the genome could be used in the search for
      genetic links between arterial hypertension and a chromosomal locus.

PMID- 10067129
TI  - [Arterial hypertension in childhood and adolescence].
AB  - The importance of hypertension in the pediatric population is not as well
      appreciated as in adults. This might well be related in part to the lower
      prevalence of high blood pressure in this age group. As with height and weight,
      blood pressure increases with age during childhood. 'High normal' blood pressure
      is a blood pressure above the 90th percentile and established hypertension a
      blood pressure above 95th percentile. The varying arm and thigh sizes of children
      and adolescents require blood pressure cuffs that are appropriately sized. A cuff
      that is too small will produce an artificially elevated blood pressure, while a
      cuff that is too large is not likely to obscure hypertensive levels of blood
      pressure. The use of an oscillometric device is more convenient for infants. The
      underlying causes of significant hypertension in the pediatric population differ
      considerably from those of adults: while the prevalence of hypertension in
      pediatrics is lower than in adults, clinically identifiable causes of
      hypertension account for a much higher proportion of hypertension in children.
      Children with chronic secondary hypertension will require drug therapy with
      converting-enzyme inhibitors, calcium-channel blockers, beta-blockers or
      diuretics. Therapy now tends to be initiated with converting-enzyme inhibitors
      because they are generally effective and have few side effects. Persistent cough
      sometimes develops on converting enzyme inhibitors. The term sartans denotes a
      new group of orally active antagonists of the angiotensin II receptor. Since
      sartans do not cause cough, these agents represent a promising treatment for
      patients who develop cough with converting enzyme inhibitors.

PMID- 10067130
TI  - [Hypertension in the elderly].
AB  - This article summarizes current recommendations for work-up and treatment of
      hypertension in elderly persons. The prevalence of hypertension in older persons
      is over 50 percent. A review of randomized controlled studies among older persons
      shows that treatment of hypertension reduces the risk of cardiovascular
      complications by about 30 to 50 percent. Since the absolute risk of
      cardiovascular disease at any given level of blood pressure in the elderly is
      three to four times greater than that in younger people, the potential benefit of
      antihypertensive treatment among older people is high. On the other hand, the
      potential risks of antihypertensive therapy need to be taken into account. The
      patients' other risk factors, pre-existing cardiovascular disease, and competing
      comorbid illnesses should be considered for treatment decisions. Baseline and
      follow-up control for detection of postural hypotension is emphasized.

PMID- 10067131
TI  - [Antihypertensive therapy in diabetes mellitus].
AB  - Approximately 150 million people worldwide have diabetes mellitus, of whom 90%
      are type II diabetics. It is therefore of no surprise that diabetic nephropathy
      has become the leading cause of end-stage renal disease. Opposite to what has
      been known previously, kidney disease is at least as common in type II as in type
      I diabetes. However, because the majority of type II diabetics has hypertension
      for many years before diabetes mellitus becomes clinically relevant, renal
      lesions are often heterogeneous with frequent exclusive presence of ischemic
      changes. For the treatment of hypertension in diabetics without nephropathy (no
      microalbuminuria), drugs that exert beneficial effects or are at least neutral
      with respect to lipid and glucose metabolism, such as ACE inhibitors, angiotensin
      II-receptor antagonists, non-dihydropyridine-calcium channel blockers and the
      thiazide-like indapamide, are to be preferred. Although metabolically neutral,
      dihydropyridine calcium channel blockers should be used with caution, since an
      increase in cardiovascular morbidity and mortality in type II diabetics treated
      with these compounds has most recently been described. Once that diabetic
      nephropathy is established, blood pressure should be lowered to 120/80 mmHg
      (measured in seated position). Antihypertensive treatment should primarily be
      based on ACE inhibitors; angiotensin II-receptor antagonists are a valuable
      alternative if ACE inhibitors are not tolerated. Both ACE inhibitors and
      angiotensin II-receptor antagonists should be used with high caution in elderly
      patients with severe atherosclerosis in whom acute renal failure could occur due
      to the presence of bilateral renal artery stenosis. Newer studies indicate that
      non-dihydropyridine calcium channel blockers such as verapamil and diltiazem may
      be as effective as ACE inhibitors in preserving renal function in diabetic
      nephropathy. A fix-dose combination of the ACE inhibitor trandolapril with
      verapamil is now available; it should be reserved for patients whose blood
      pressure and/or proteinuria can not be adequately controlled with ACE inhibitors.
      Finally, indapamide is the only antihypertensive diuretic with nephroprotective
      properties.

PMID- 10067132
TI  - [Fixed antihypertensive drug combinations].
AB  - Arterial hypertension is a highly heterogeneous condition. It is therefore not
      surprising that blood pressure lowering agents acting via a given mechanism allow
      a normalization of blood pressure in a fraction of hypertensive subjects only.
      The combination of drugs with different mechanisms of action on the
      cardiovascular system results in a considerably higher antihypertensive efficacy,
      not only with regard to the absolute blood pressure reduction but also in the
      number of responders. This effect is not achieved at the expenses of tolerance,
      because usually lower doses of the combined agents are sufficient to achieve the
      target blood pressure. The administration of antihypertensive agents in fixed
      combination has the advantage of its simplicity for both the physician as well as
      the patient. This aspect also explains the increasing popularity of fixed
      combinations as a valuable option in the initial treatment of the hypertensive
      patient.

PMID- 10067133
TI  - [Perioperative management of patients with arterial hypertension].
AB  - Concomitant arterial hypertension in surgical patients is an indicator of
      increased risk for peri-operative cardiovascular complications. This review
      article discusses reasons for the increased risk and gives recommendations for
      the perioperative management of patients with arterial hypertension. In patients
      with established anti-hypertensive therapy, it is of greatest importance to
      continue this therapy perioperatively. In addition, the management of patients
      with preoperatively elevated arterial blood pressure is addressed, and
      recommendations are provided as to when it seems safe to go on with surgery and
      when prudent to delay surgery to control hypertension.

PMID- 10067134
TI  - [Calcium antagonists in cardiovascular diseases--a valuable controversy, but
      unnecessary panic].
AB  - Taking into consideration the available data in 1998, we believe that short
      acting calcium antagonists should no longer be used in hypertensive patients. The
      practice of using oral or sublingual nifedipine in hypertensive emergency or
      pseudoemergency should be abandoned because it can lead to serious side effects
      such as syncope, myocardial infarction, stroke and even death. However, the use
      of a low dose of the long-acting formulations seems to be safe and promising in
      patients with essential hypertension. In the Hypertension Optimal Treatment (HOT)
      trial a calcium-antagonist based combination therapy reduced blood pressure by
      over 20 mmHg in most of the nearly 19,000 patients. Cardiovascular mortality in
      this study was with 3.8 per 1000 patient years clearlylower as compared to 6.5
      per 1000 patient years reported in previous intervention trials. A long-acting
      dihydropyridine calcium antagonist was used in 78% of these patients. Clearly the
      calcium antagonists controversy was helpful in alerting physicians to the fact
      that hypertension remains a surrogate endpoint and that not all drugs that reduce
      blood pressure will reduce morbidity and mortality to the same extent. What was
      completely unnecessary, however, was the inappropriate news media coverage to the
      calcium blocker controversy that led to panic and confusion among patients and
      frustration among physicians. In this context we should perhaps remember the
      first rule in the treatment of Sir George Pickering: "Never frighten your
      patients."

PMID- 10067135
TI  - [Does constitutional hypotension exist?].
AB  - Orthostatic hypotension is frequently related to severe insufficiency of the
      autonomic nervous system associated with neuropathy or systemic disease like
      diabetes. Inversely, pre-syncopal orthostatic symptoms associated with mild drop
      in orthostatic blood pressure is quite often a reason to seek medical care, but
      is relatively unrecognized in the literature. Recently a syndrome of mild
      orthostatic intolerance has been defined, and seem to be quite common among young
      subjects, characterized by frequent orthostatic presyncopal symptoms associated
      with orthostatic tachycardia and high plasma catecholamines levels. In the paper,
      we will review different causes of orthostatic hypotension, and mention some
      physiopathological mechanisms linked to renal sodium handling. In particular,
      alterations in renal proximal segmental handling of sodium might generate and
      play a pathophysiological role in maintenance of the orthostatic hypotension.
      Finally, we will evoke some therapeutical aspects.

PMID- 10067136
TI  - [Arterial hypertension and rapidly progressing renal failure].
AB  - A case report is presented, which describes a patient with a long history of
      stable but mild renal insufficiency for several years, who presented with end
      stage stage renal disease following a rapid decline of renal function and
      accelerated hypertension. A renal work-up disclosed severe bilateral renal artery
      stenoses. A percutaneous transluminal renal angioplasty (PTRA) with stent
      significantly improved both renal function and hypertension and the patient was
      still not on dialysis twelve months after the procedure. The epidemiology,
      prognosis, diagnosis and treatment of the atherosclerotic renovascular disease
      are discussed. Treatment consists in the revascularization, this can improve not
      only the hypertension but also the renal function. In patients with end-stage
      renal disease PTRA can postpone for several months the need for dialysis.

PMID- 10067137
TI  - [Intersensory facilitation: also concomitant visual stimuli can decrease reaction
      time].
AB  - Subjects respond faster to a visual response signal when an auditory accessory is
      presented at the same time. In contrast, a visual accessory does not reduce
      reaction time to an auditory response signal. Previous studies suggest that this
      asymmetrical effect is due to different properties of visual and auditory
      accessories (i.e., arousal and preparation enhancement). We assessed whether this
      asymmetrical effect would disappear when subjects were to process the accessory
      stimulus in a secondary task while responding to the response signal in the main
      task. This dual task method formed the basis for two experiments. Each experiment
      employed both visual and auditory accessories, as well as auditory and visual
      response signals. Experiment 1 manipulated factorially the intensity levels of
      the accessory and response signal. Experiment 2 was similar to Experiment 1 but
      manipulated the time interval between the accessory and the response signal
      instead of stimulus intensities. Response force was recorded in addition to
      reaction time. In both experiments the previously reported asymmetrical effect
      disappeared showing that auditory and visual accessories are functionally
      equivalent when the task demands more central processing of these stimuli. The
      analysis of response force suggested that both the visual and auditory accessory
      produce nonspecific arousal effects that may facilitate the generation of the
      response.

PMID- 10067138
TI  - [Inducibility of olfactory sensitivity by odor exposure of persons with specific
      anosmia].
AB  - Insensitivity to single odors, called specific anosmia, has been repeatedly
      reported in the literature. The main question of the present study was whether
      olfactory sensitivity is inducable in subjects with specific anosmia. For this
      reason the olfactory sensitivity of women with specific anosmia to the volatile
      steroid androstenone was investigated by threshold measurements at two times,
      before and after repeated odor exposure. Androstenone is a compound that
      contributes to human body odor and is found at a higher concentration in male
      axillary sweat than in female sweat. The results show that in more than 80% of
      the odor exposed anosmics olfactory perception of androstenone could be induced.

PMID- 10067139
TI  - [Effect of symptom-related vs. distraction-focused attention on dysphoric mood].
AB  - Within the framework of the "response styles theory" Nolen-Hoeksema (1991) argues
      that depressive episodes are prolonged or intensified by symptom-focused
      rumination. In contrast, depressed mood can be reduced by responses which focus
      the attention away from the symptoms of depression and its possible causes and
      consequences. In the present study these assumptions were examined under
      conditions derived from a critical analysis of earlier empirical studies. 70
      students took part in the experiment. Depressed (n = 30) and non-depressed (n =
      40) subjects were randomly assigned to either a symptom-focused or a distracting
      task. Self-report data were used to compare pre- and post-task mood. Results are
      mainly consistent with predictions. However, in contrast to the findings of Nolen
      Hoeksema and her colleagues, no significant increase in depressed mood was
      observed in the symptom-focused condition and the empirical effect in the
      distracting condition was weaker than in previous studies using the same
      distracting task. These inconsistent findings are attributed to differences in
      the experimental settings. Theoretical and methodical implications are discussed.

PMID- 10067140
TI  - Aortic aneurysms. Detecting and treating enlarged blood vessels.

PMID- 10067141
TI  - Health tips. Reducing allergens in your home.

PMID- 10067142
TI  - More caution advised in using impotence drug Viagra.

PMID- 10067143
TI  - Small unruptured brain aneurysms may not require surgery.

PMID- 10067144
TI  - Loss of height. When should you become concerned?

PMID- 10067145
TI  - Making health a priority. It's a key to living longer.

PMID- 10067146
TI  - Gallstones. A common, sometimes serious condition.

PMID- 10067147
TI  - I often develop canker sores in my mouth. Is there anything I can do to treat
      them?

PMID- 10067148
TI  - Are there any foods I can eat to help protect my eyesight?

PMID- 10067149
TI  - Medicare. Fraud busters.

PMID- 10067150
TI  - Columbia watch. Tamer ... not timid.

PMID- 10067151
TI  - Outreach. Good mourning.

PMID- 10067152
TI  - Consolidation. Trauma trouble.

PMID- 10067153
TI  - Should Congress pass a patient-protection law?

PMID- 10067154
TI  - Comebacks. Talent route.

PMID- 10067155
TI  - Conflicts of interest during a financial crisis.

PMID- 10067156
TI  - Shock talk. Interview by Alden Solovy.

PMID- 10067157
TI  - The unlearning curve. Learning is only half the process of achieving
      organizational change.

PMID- 10067158
TI  - Off target.
AB  - Leave it to the market. It's our collective corrective, the American way of
      problem-solving. So it's no surprise that we looked to the market to stop runaway
      health care costs. For awhile, it seemed to work. Medicare HMOs, physician
      practice management, risk contracting, and other innovations boomed. Then came
      the setbacks, exposing health care's complexities and contradictions--and
      reminding us that nothing escapes market discipline.

PMID- 10067159
TI  - 1999 Nova Award winners.
AB  - No hospital creates a healthier community all by itself. But it can give its
      neighbors a jump start. As the winners of this year's NOVA Awards show, the
      result is a better life for the most vulnerable--the sickest, the poorest, the
      youngest, the oldest. And by tackling problems beyond their traditional turf,
      NOVA winners earn raves for leadership.

PMID- 10067160
TI  - Benchmarking guide '99.
AB  - The right data: You can't benchmark without it. For our third annual guide to
      benchmarking under managed care, we turned to six prominent organizations. We've
      tapped their databases and creativity to help you gauge your performance on
      financial, operational, and service targets by degree of managed care
      penetration.

PMID- 10067162
TI  - Techno no-nos. Think you've mastered those gadgets around you? Think again.

PMID- 10067161
TI  - Wish lists: 1999 lobbying outlook.
AB  - It's an uncertain year for Congress, but the health agenda is already filling in
      with both big-picture and nitty-gritty concerns. From patient protection to
      patents, health care's top advocacy groups describe what they want most from
      Washington. As the legislative season gets under way, here's what they'll lobby
      for.

PMID- 10067163
TI  - Production of donor-derived offspring by transfer of primordial germ cells in
      Japanese quail.
AB  - We transfused concentrated primordial germ cells (PGCs) of the black strain (D:
      homozygous for the autosomal incomplete dominant gene, D) of quail into the
      embryos of the wild-type plumage strain (WP: d+/d+) of quail. The recipient quail
      were raised until sexual maturity and a progeny test of the putative germline
      chimeras was performed to examine the donor gamete-derived offspring (D/d+).
      Thirty-one percent (36/115) of the transfused quail hatched and 21 (13 females
      and 8 males) of them reached maturity. Five females and 2 males were germline
      chimeras producing donor gamete-derived offspring. Transmission rates of the
      donor derived gametes in the chimeric females and males were 1.8-8.3% and 2.6
      63.0%, respectively. Germline chimeric and the other putative chimeric males were
      also test-mated with females from the sex-linked imperfect albino strain (AL:
      d+/d+, al/W, where al indicates the sex-linked imperfect albino gene on the Z
      chromosome, and W indicates the W chromosome) for autosexing of W-bearing
      spermatozoa: No albino offspring were born.

PMID- 10067164
TI  - Macroscopic distribution of coronary atherosclerotic lesions in cholesterol-fed
      rabbits.
AB  - In the present study we macroscopically examined a change in the distribution of
      coronary atherosclerosis in cholesterol-fed rabbits. Rabbits were fed a
      cholesterol-enriched diet for 15 weeks, then replaced by a normal diet, and were
      sacrificed at 15, 24, 32 and 42 weeks after the start of the experiment. The
      coronary atherosclerosis in the cholesterol-fed rabbits was distributed more
      densely in the proximal portion than in the middle and distal portions, and the
      lesions were severe at 24 and 32 weeks after the start of the experiment.
      comparison of lesions in the three portions at these time points showed that the
      percentages of lesion areas in the proximal portion, the middle portion and the
      distal portion were approximately 51%, 21 to 25% and 0.2 to 3.7%, respectively.
      Macroscopic observation of the coronary atherosclerotic lesions showed that the
      lesions formed over the vessel lumen in the proximal portion within the range of
      approximately 5 mm from the orifice of the left coronary artery. In the middle
      portion, the lesions formed predominantly around the orifices of branches as
      small patchy lesions from 1 to 3 mm in diameter. These findings support previous
      histopathological reports that suggested that the incidence of stenosis in the
      proximal portion was high, and the incidence of lesion occurrence in the middle
      and the distal portions varied. The method, macroscopical investigation of the
      coronary artery, is useful for analyzing coronary atherosclerosis in the rabbit.

PMID- 10067165
TI  - Morphological variations in transplanted tumors developed by inoculation of
      spontaneous mesothelioma cell lines derived from F344 rats.
AB  - Morphological and immunohistochemical features of the abdominal mesotheliomas
      that were developed by inoculation of 3 cell lines (MeET-4, -5 and -6)
      established from spontaneous abdominal mesotheliomas in male F344 rats. Although
      the original tumors of three cell lines showed signs of epithelioid growth with a
      predominantly simple papillary pattern, transplanted tumors revealed a variety of
      morphologic features including epithelioid with glandular structures,
      sarcomatous, and a mixture of these components. All tumor cells of transplanted
      tumors were positive for alpha-smooth muscle actin (ASMA) but almost negative for
      desmin as were epithelioid cells of the original tumors, and the cell lines were
      positive for desmin but not for ASMA. These results suggested that mesothelioma
      in the F344 rat had the potential for wide spectrum differentiation under in
      vitro conditions. The microenvironmental factors obtained in vivo can modify
      their potential ability and their morphological aspects. These factors may be
      related to tumor cell reexpression of ASMA of tumor cells that were masked under
      in vitro culture conditions.

PMID- 10067166
TI  - Age-related changes in blood coagulation and fibrinolysis in mice fed on a high
      cholesterol diet.
AB  - To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we
      examined age-dependent changes in platelet activity, blood coagulation and
      fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male
      ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days
      with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'
      diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated
      aggregation compared with the same in control mice. Yohimbine as alpha 2
      adrenergic blocker antagonized these aggregations in a dose-dependent manner. A
      significant increase in plasma total cholesterol and VLDL (very low-density
      lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight
      ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the
      early phase of this experiment, a significant increase in fibrinogen was
      observed. In the middle phase, increases in the activity of antithrombin III
      (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content
      gradually decreased in both normal diet and HCD mice throughout the experiment.
      The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD
      mice. Morphological observation of the aortic arch from 3-month HCD mice revealed
      apparent atheromatous plaques not seen in control mice. These results suggest
      that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic
      model and the changes in platelet activity, coagulation and fibrinolysis in the
      early phase may be a cause of pathologic changes in this model.

PMID- 10067167
TI  - Age-related changes in antioxidant enzyme activities in the small intestine and
      liver from Wistar rats.
AB  - The present study was designed to determine age-related changes in intestinal and
      hepatic antioxidant enzymes including superoxide dismutase (SOD), glutathione
      peroxidase (GSH-PX), and glutathione-S-transferase (GST), and lipid peroxidation
      in male Wistar rats (n = 8) aged 2 wk, 2.5 mon, 5 mon, 10 mon, and 23 mon. In the
      small intestine, cytosolic SOD, GSH-PX activities and lipid peroxidation were not
      affected by age, but intestinal GST activity was noticeably enhanced as age
      increased. In particular, intestinal GST activity in 23 mon old rats was 3 times
      as strong as that in 2 wk old rats. In the liver, the activity of hepatic
      cytosolic SOD was not affected by age, whereas GSH-PX and GST activities in rats
      aged 10 mon and 23 mon were much stronger than those in rats aged 2 wk, 2.5 mon,
      and 5 mon. The increased lipid peroxidation in 2.5 mon and 5 mon old rats was
      observed when compared with that of other groups. It is therefore concluded from
      the results presented here that age greatly increases GST activity in the small
      intestinal mucosae and increasing GSH-PX, GST activities and lipid peroxidation
      in the liver from male Wistar rats.

PMID- 10067168
TI  - Characteristics of spontaneous erythema appeared in hairless rats.
AB  - The hairless rat (WBN/Kob-Ht), a dominant mutant rat derived from the Wistar
      strain, rarely develops spontaneous erythema of a progressive nature on its skin.
      Erythema was first observed at 8 weeks of age and the incidence at 20 weeks of
      age was about 4% in both males and females. Histopathologically, erythema was
      characterised by dermatitis induced by an immunological reaction. Areas of
      erythema in the skin were decreased by treatment with dexamethasone (1 mg/kg) or
      ciclosporin (25 or 50 mg/kg). These results suggested that erythema on the
      hairless rat could be used as an animal model of spontaneous dermatitis.

PMID- 10067169
TI  - Preventive effects of dehydroepiandrosterone acetate on the fatty liver induced
      by orotic acid in male rats.
AB  - Preventive effects of dehydroepiandrosteone acetate (DHEA-A) and clofibrate
      (positive control substance) on the fatty liver induced by orotic acid (OA) were
      examined on the male Sprague-Dawley rats fed a high sucrose based diet containing
      1% OA and this diet further mixed with 0.5% DHEA-A or 0.5% clofibrate for 2
      weeks. Numerous lipid droplets were observed in the hepatocytes of the rats
      treated with OA alone, but not in those treated with DHEA-A or clofibrate. In
      comparison to the group with OA alone, the DHEA-A or clofibrate treated rats
      showed a larger relative liver weight (to body weight) which was accompanied by
      increased peroxisomes in the hepatocytes. These results indicate that DHEA-A, as
      well as clofibrate, may prevent OA-induced fatty liver.

PMID- 10067170
TI  - Application of nested polymerase chain reaction to detection of mouse hepatitis
      virus in fecal specimens during a natural outbreak in an immunodeficient mouse
      colony.
AB  - The usefulness of RT-PCR for the detection of MHV in tissues and feces of
      experimentally infected animals has been reported, but it was unclear whether the
      method was also applicable for the detection of MHV during a natural outbreak.
      Enterotropic infection is considered to be the most common form of natural
      infection among various forms of MHV infection. In this paper, RT-nested PCR was
      performed to detect MHV excreted in the feces during an outbreak in an
      immunocompromised A/WySnJ mouse colony. The expected bands were amplified after
      nested PCR from 20 fecal samples out of 37. These results showed that RT-nested
      PCR could be applicable for the diagnosis for MHV natural infection.

PMID- 10067171
TI  - Nucleotide sequence of endothelin-B receptor gene reveals origin of piebald
      mutation in laboratory mouse.
AB  - Piebald (Ednrbs) is a coat color mutation of laboratory mice caused by a
      decreased expression of endothelin-B receptor gene (Ednrb). The IITES and JF1
      mouse strains, whose origins are believed to be different from those of the
      common laboratory inbred strains, also show a phenotype similar to Ednrbs. In the
      present study, we found that the nucleotide sequence of the Ednrb gene of the
      IITES and JF1 mice is identical to that of the Ednrbs allele, Ednrbs allele has
      an RFLP of the Ednrb gene identical with that of M. m. molossinus but different
      from other subspecies, and at least particular regions of chromosome 14 proximal
      to the Ednrb locus of the IITES and JF1 strains are derived from M. m.
      molossinus. These findings clearly indicate that the Ednrbs allele of the
      laboratory mice has its origin in M. m. molossinus.

PMID- 10067172
TI  - Intraperitoneal insemination of the guinea pig with synchronized estrus induced
      by progesterone implant.
AB  - Female guinea pigs with synchronized ovulation by means of implantation of
      progesterone-filled tubing (P-tube) followed by a progesterone injection, were
      inseminated by intraperitoneal injection with sperm suspension. First, to obtain
      the optimum conditions for insemination, the females were inseminated singly over
      the range of 1-10 x 10(7) spermatozoa before and after the synchronized
      ovulation. The incidence of conception and implantation was 100% in the females
      given more than 5 x 10(7)/animal at 9:00 h on the 5th day after removal of the P
      tube. Second, the reproductive ability of the inseminated females under this
      optimal condition was observed throughout the pregnancy to delivery. Inseminated
      females had a mean +/- S.D. gestation period of 68.7 +/- 0.5 days, a litter size
      of 2.8 +/- 0.6 pups and body weight of 110 +/- 14 g. These data were comparable
      to those of naturally-mated females. Our findings suggest that the artificial
      insemination by intraperitoneal injection in combination with the synchronized
      estrus technique is very useful for production control in a small colony of
      guinea pigs.

PMID- 10067173
TI  - Midpalatal suture of osteopetrotic (op/op) mice exhibits immature fusion.
AB  - The midpalatal suture was observed histologically in both toothless osteopetrotic
      (op/op) and normal (control) mice. The normal mice had a mature sutural
      structure, which consists of a well-developed cartilage cell zone and palatal
      bone. In contrast, the thickness of the cartilage cell zone was substantially
      greater in the op/op mice than that in the controls. Moreover, the cartilage
      cells in the op/op mice were frequently found in the palatal bone as well as in
      the sutural space, exhibiting an imperfect fusion. It seems that immature fusion
      at the sutural interface in the op/op mice is related to a decrease in biting or
      masticatory force accompanied by the failure of tooth eruption in addition to an
      essential defect in osteoclast differentiation, which is a congenital symptom in
      op/op mice.

PMID- 10067174
TI  - Mapping of the genes for rat P-glycoprotein 1, 2, and 3 (Pgy1, Pgy2, and Pgy3) to
      chromosome 4.

PMID- 10067175
TI  - Reuse of single-use only devices.

PMID- 10067176
TI  - A manufacturer's perspective: Hewlett Packard Y2K action plan.
AB  - Medical device manufacturers must ensure that their devices are safe and
      effective including investigating issues involved with the century rollover.
      Manufacturers must begin early to evaluate their products in order to allow time
      to correct and distribute these product corrections and communicate to their
      customers so they can prepare for the Y2K event.

PMID- 10067177
TI  - Preparing hospital medical devices for year 2000: a risk analysis approach.

PMID- 10067178
TI  - Mobile phones in hospitals.

PMID- 10067179
TI  - Technological developments and approaches to improving service quality.
AB  - In summary, major paradigm shifts in the health care industry are altering the
      way technology is maintained and supported. Service organizations are now
      responsible for maintaining a broader base of technology within the health care
      delivery network and must to this on an extremely rapid, efficient, and
      productive basis. A number of new technologies are coming on-line, which can
      allow a health care technology service organization to experience significant
      improvements in profitability, efficiency, and productivity. To realize maximum
      benefit from these technologies, service organizations may find themselves re
      engineering their service processes. The author believes that this is a
      requirement for many service organizations, regardless of whether new technology
      is implemented. The traditional approaches to service delivery are ineffective in
      managing the new structural realities and service requirements of today's health
      care environment. New strategies and tactics are required for ensuring that these
      requirements are met. These approaches will no doubt improve the overall quality,
      productivity, and efficiency of service and are based on best practices utilized
      by leading OEMs and ISOs in the medical electronics and other high technology
      service industry such as information technology and telecommunications, where the
      service organization is responsible for supporting a broad array of the
      technology over a large geography with a densely populated installed base, not
      unlike the typical health care delivery service environment. Once operational
      improvements are made, a service organization can take advantage of the
      productivity and efficiency gains brought on by new technology. Organizations
      interested in doing so are urged to thoroughly research the current state-of-the
      art and best practices, because there are numerous systems currently available
      off-the-shelf. The author believes that new technology will be a basic
      requirement for competing in the health care technology service marketplace,
      because it can significantly affect the profitability of service organizations.
      This technology will help level the playing field between ISOs, OEMs, and
      biomedical personnel. As our research suggests, efficiently operating biomedical
      personnel can achieve a significantly higher utilization and profitability than
      efficiently operating OEMs, due to the advantages of lower overhead and operating
      cost structure. In general, the process to improve service productivity and
      efficiency involves a review of current service operations and understanding of
      the customer environment perceptions as well as understanding of key service
      factors parameters. From there, service organizations should identify the current
      state-of-the-art service and infrastructure systems and technology. Based on this
      assessment, a service organization can evaluate best practices and identify new
      strategies and tactics for improving service delivery. Through better service
      management control and education of users on the improvement in service, which
      the new processes and technologies provide, the service organization can realize
      real, quantifiable improvements in service quality, productivity, and
      profitability.

PMID- 10067180
TI  - Learning from a merger opportunity.

PMID- 10067181
TI  - Accuracy relationship of blood pressure devices between the AAMI SP 10 standard
      and the British Hypertension Society protocols.
AB  - This article analyzes and compares the accuracy requirements for the AAMI SP10
      standard and the British Hypertension Society (BHS) protocol for evaluation of
      blood pressure devices. It generates a theoretical mapping relationship between
      the AAMI accuracy criteria and the BHS grading system, using these requirements.
      It locates within that relationship the analyses of blood pressure devices in the
      literature that have used both of these standards from 1990, when the original
      BHS protocol was published and the original AAMI SP10 standard was available,
      through the end of 1997. Comparison of 67 paired entries thus provides a
      framework for consideration of the concept of accuracy implicit in both systems
      against empirical testing of devices. Results of accuracy testing with each of
      the two systems should be consistent and convertible to the other system. The
      discrepancies between the theoretic combination of accuracy standards and
      empirical testing for each standard separately suggest a variety of difficulties
      in determining accuracy, such as statistical variability and test procedure
      variations. Using a chi-square test for matched samples, the discrepancies are
      found statistically significantly different (chi-square = 28.96, p < 0.001).
      Although there are fewer literature reports using the revised BHS protocol, the
      differences in the two systems suggest a potential need for an international
      agreement on accuracy determinations of blood pressure devices.

PMID- 10067182
TI  - Comparative study of physical properties of three suture materials: silk, e-PTFE
      (Gore-Tex), and PLA/PGA (Vicryl).
AB  - The aim of this in-vitro study was to compare the physical properties of three
      suture materials used in periodontal surgery: silk, expanded
      polytetrafluoroethylene (e-PTFE), and polylactic acid/polyglycolic and (PLA/PGA).
      Five physical tests were carried out on each of the three suture materials:
      strain to failure, tensile strength, knot tensile strength, knot slippage, and
      capillarity. For each test, 30 samples of each suture material were used. In all
      cases, the statistical results showed that the e-PTFE and the PLA/PGA threads
      were superior.

PMID- 10067183
TI  - An ultra-high common-mode rejection ratio (CMRR) AC instrumentation amplifier for
      laplacian electrocardiographic measurement.
AB  - Laplacian electrocardiograms (LECGs) localize the moment of activation (MOA) of
      the heart noninvasively at a nearby point on the chest surface. Tripolar
      concentric ring (TCR) electrodes provide small, but well-defined, site-specific
      second spatial derivative signals of the potential on the chest surface for
      studying the activation sequence of the myocardium. A battery-powered, modified
      AC instrumentation amplifier (IA) was used as preamplifier to obtain signals with
      a high common-mode rejection ratio (CMRR). The authors' direct-coupled quasi-high
      pass IA has high input impedance and high CMRR, without the need to match
      capacitors and resistors. The amplifier circuit and two lithium cells were
      integrated with the substrate for the TCR sensor to minimize inductive pickup by
      the leads. Combining the natural ability of the TCR electrodes to reject common
      mode signals with the high CMRR of the IA made it possible to obtain LECG signals
      in real time with good signal-to-noise ratio (SNR). The authors observed and
      recorded the MOAs from 16 sites in a 4-by-4 matrix from the left side of the
      thorax of each subject. Beat-by-beat changes were observed from one subject
      showing episodes of bigeminal rhythm. The authors were able to obtain localized
      signals representing the right and left ventricles from surface TCR electrodes in
      real time.

PMID- 10067184
TI  - Voices from the silent world of doctor and patient.

PMID- 10067185
TI  - Autonomy, power, and control in palliative care.

PMID- 10067186
TI  - Stewardship of the aged: meeting the ethical challenge of ageism. In honor of
      Joseph Fletcher.

PMID- 10067188
TI  - Giving "moral distress" a voice: ethical concerns among neonatal intensive care
      unit personnel.

PMID- 10067187
TI  - Neonatal viability in the 1990s: held hostage by technology.

PMID- 10067189
TI  - Ethical challenges in the treatment of infants of drug-abusing mothers.

PMID- 10067190
TI  - Precedent autonomy: life-sustaining intervention and the demented patient.

PMID- 10067191
TI  - Proxy, health, and personal care preferences: implications for end-of-life care.

PMID- 10067192
TI  - CQ sources/bibliography.

PMID- 10067193
TI  - Universal emergency access under managed care: universal doubt or mission
      impossible?

PMID- 10067194
TI  - Science, rhetoric, and public discourse in genetic research.

PMID- 10067195
TI  - Response to "Euthanasia and health reform in Canada" by Michael Stingl (CQ vol 7,
      no 4). Euthanasia and justice.

PMID- 10067196
TI  - Response to special section: cloning: technology, policy, and ethics (CQ vol 7,
      no 2). Humanness, personhood, and a lamb named Dolly.

PMID- 10067197
TI  - Environmental ethics and medical ethics: some implications for end-of-life care,
      Part II.

PMID- 10067198
TI  - A modern public health crisis: a physician speaks about healthcare in post
      Glasnost Russia. Interview by Steve Heilig.

PMID- 10067199
TI  - Development of atherosclerotic lesions in cholesterol-loaded rabbits.
AB  - To examine both of the target vessels and the optimal time of their endothelial
      denudation to study vascular restenosis after balloon injury in cholesterol
      loaded rabbits, we made 36 atherosclerotic rabbits by feeding a hypercholesterol
      diet, and histologically examined the onset time and the development of
      atherosclerosis. Atheromatous changes were observed first after the 5th week in
      the thoracic aorta from the start of the diet, and then extended to the abdominal
      aorta, coronary artery with time. The atherosclerotic lesions in the thoracic
      aorta and the proximal portion of the coronary artery showed high-grade
      concentric intimal thickening with luminal stenosis. The abdominal aortic lesion
      mildly progressed. In the renal, carotid and femoral arteries, in contrast,
      slight atheroscleromatous changes developed during the diet period. These results
      suggest that the thoracic and abdominal aortas and the coronary artery would be
      suitable as target vessels to study vascular restenosis after balloon injury, and
      the endothelial denudation of these vessels should be performed between the 8th
      and 15th week in this diet protocol for an accurate analysis.

PMID- 10067200
TI  - High-temperature effects on antibody response to viral antigen in mice.
AB  - To determine the effects of high-temperature exposure on antibody response to
      viral antigen in mice, male BALB/c mice were placed for 13 days in animal
      chambers at 23 degrees C, 32 degrees C, and 35.5 degrees C. Rectal temperature
      rose from 37 degrees C to 39 degrees C on day 1 in a 35.5 degrees C environment.
      The rectal temperature was kept constant throughout the exposure period. The IgG
      antibody to Sendai virus (SV) antigen was inhibited to about 50% of the control
      value (23 degrees C). The serum corticosterone concentration indicating thermal
      stress increased steadily, peaking on day 1 and then gradually decreased and
      recovered to the normal level on day 13. Body weight decreased to about 72% of
      the controls on day 13. Thymus and spleen weight decreased to 31.7% and 61.5%
      respectively. At 32 degrees C, these effects were less than at 35.5 degrees C.
      Effects of high-temperature exposure at 35.5 degrees C appeared to noticeably
      decrease thymus and spleen weight. It is clear that IgG-antibody response to SV
      antigen is suppressed by high-temperature exposure.

PMID- 10067201
TI  - Effectiveness of indomethacin as an antitumor agent in Colon 26-bearing
      conventional and nude mice, and telomerase activity in the tumors.
AB  - The antitumor effect of indomethacin on Colon 26 tumor was investigated in
      conventional (CDF1) and nude mice (BALB/c nu/nu), and the telomerase activity in
      the tumor tissues treated with indomethacin was monitored. Growth of Colon 26
      tumor was significantly suppressed with indomethacin treatment compared to the
      controls both in conventional and nude mice. And telomerase activity in the tumor
      tissues noticeably declined in contrast to normal somatic tissues (testis, liver
      and colon), which were not affected by indomethacin treatment. We also showed
      that indomethacin can suppress tumor growth in association with a preferential
      decrease in telomerase activity in tumor tissues both in conventional and nude
      mice to the same extent. This study suggests a method for investigating the
      mechanism of tumor suppression by indomethacin, and suggests that indomethacin
      might be useful as a novel agent for human cancer therapy.

PMID- 10067202
TI  - Glycoconjugate expression in follicle-associated epithelium (FAE) covering the
      nasal-associated lymphoid tissue (NALT) in specific pathogen-free and
      conventional rats.
AB  - We examined lectin-histochemically the glycoconjugate expression in the follicle
      associated epithelium (FAE) covering the nasal-associated lymphoid tissue (NALT)
      in the rat under specific pathogen-free (SPF) and conventional (CV) conditions
      and compared the results for SPF and CV rats as well as for membranous (M) cells
      and adjacent ciliated respiratory epithelial (CRE) cells in FAE. N
      acetylgalactosamine-specific lectins, Dolichos biflorus (DBA), Helix pomatia
      (HPA), Glycine max (SBA) and Vicia villosa (VVA), and alpha-L-fucose-specific
      lectin, Ulex europaeus (UEA-I), preferentially bound to M cells mainly in the
      luminal surface compared with CRE cells in SPF rats, whereas DBA and UEA-I showed
      signs of preferential binding to the apical and basolateral cytoplasm as well as
      to the luminal surface of M cells in CV rats. In addition, HPA, SBA and VVA more
      frequently and extensively labeled M cells than CRE cells in CV rats with the
      same subcellular staining pattern as DBA and UEA-I. On the whole, the changes in
      lectin binding frequency and strength were more prominent in M cells than in CRE
      cells in both SPF and CV rats. The present results indicate that DBA and UEA-I
      are useful as markers of M cells in NALT. Furthermore, the pattern of expression
      of carbohydrate residues recognized by such lectins in SPF and CV rats suggests
      that M cells are highly sensitive to environmental changes.

PMID- 10067203
TI  - Anatomical structure and surface epithelial distribution in the nasal cavity of
      the common cotton-eared marmoset (Callithrix jacchus).
AB  - To validate use of the common cotton-eared marmoset (Callithrix jacchus) in
      inhalation toxicity studies, its nasal morphology was examined. The nasal
      turbinates each consisted of one maxilloturbinate and one ethmoturbinate: these
      were more planar in structure than the comparable structures of rodents or dogs.
      The nasal cavity epithelia comprised squamous epithelium (SE), nasal transitional
      epithelium (NTE), respiratory epithelium (RE) and olfactory epithelium (OE),
      listed in order of occurrence from anterior to posterior positions. NTE was
      distributed as a narrow band lying between SE and RE. OE was limited to the
      dorsal part of the cavity, which was structurally similar to that of the macaque
      or man. Overall, this study revealed structural the similarity of the whole nasal
      cavity in the marmoset to that of macaques or humans. Prediction of nasal cavity
      changes in man based on extrapolation from experimentally induced changes in the
      common marmoset therefore seems likely to be feasible, making it a useful animal
      model for inhalation studies.

PMID- 10067204
TI  - Sex differences in susceptibility of ICR mice to oral infection with
      Corynebacterium kutscheri.
AB  - Sex difference in susceptibility to oral infection with Corynebacterium (C.)
      kutscheri was experimentally studied in ICR mice. Immature (4-week-old) and adult
      (14-week-old) mice were inoculated with two infecting doses of C. kutscheri, and
      necropsied for bacteriological and serological survey 4 weeks after the bacterial
      infection. No macroscopic lesions at necropsy were demonstrated, except for one
      adult male given 10(9) bacteria. In immature mice, C. Kutscheri isolated from the
      oral cavity and cecum with FNC agar, were recovered in only 40.0% of female mice
      but in 90.0% of male mice given 10(6) bacteria (p < 0.05), and in only 55.6% of
      female mice but in 80.0% male mice given 10(8) bacteria. In adult mice given
      10(9) bacteria, the organism were recovered in only 45.5% of female mice but in
      90.9% of male mice (p < 0.05), furthermore, the mean number of organisms in the
      cecum of male mice harboring the organism was significantly higher than that in
      females (p < 0.01). Castration caused an increase in host resistance in adult
      male mice. These results indicated that ICR male mice were more susceptible than
      females, in terms of bacterial colonization in the cecum and the oral cavity, to
      oral infection with C. kutscheri.

PMID- 10067205
TI  - A genetic linkage map of rat chromosome 9 with a new locus for variant activity
      of liver aldehyde oxidase.
AB  - A genetic linkage map of rat chromosome 9 consisting of five loci including a new
      biochemical marker representing a genetic variation of the activity of the liver
      aldehyde oxidase, (Aox) was constructed. Linkage analysis of the five loci among
      92 backcross progeny of (WKS/Iar x IS/Iar)F1 x WKS/Iar revealed significant
      linkages between these loci. Minimizing crossover frequency resulted in the best
      gene order: Aox-D9Mit4-Gls-Cryg-Tp53l1. The homologues of the Cryg, Gls, and Aox
      genes have been mapped on mouse chromosome 1 and human chromosome 2q. The present
      findings provide further evidence for the conservation of synteny among these
      regions of rat, mouse, and human chromosomes.

PMID- 10067206
TI  - Underdevelopment of fetal thyroid follicular cells in athymic nude mouse
      (BALB/cAnNCrj-nu/nu) observed by electron microscopic morphometry.
AB  - Fetal thyroid follicular cells of congenitally athymic nude mouse (BALB/cAnNCrj
      nu/nu) were studied with an electron microscope. The area of the entire cell,
      nucleus and mitochondrion were measured and compared in athymic and euthymic
      fetal nude mice (BALB/cAnNCrj-nu/+) at 18 days of gestation. The mean area of
      cytoplasm was significantly smaller in homozygous athymic nude mice than in
      heterozygous euthymic ones. The mean area of the mitochondrion was also smaller
      in homozygous athymic nude mice, but the difference was not statistically
      significant. There was no significant difference between the two groups in the
      area of the nucleus. These findings suggest that the thyroid gland of athymic
      nude mice is still underdeveloped at the end of gestation as compared to that of
      their euthymic littermates.

PMID- 10067207
TI  - Evaluation of PCR as a means of identification of Pasteurella pneumotropica.
AB  - A polymerase chain reaction with new primers (new PCR) designed from Pasteurella
      pneumotropica 16S rDNA as an identification system for this organism was compared
      with the PCR reported by Wang et al. (Wang's PCR) by using 15 bacterial reference
      species and 70 clinical isolates with the conventional identification system. For
      the 15 reference strains, both PCRs were identical. For the 70 clinical isolates,
      the new PCR and Wang's PCR showed consistency with the conventional system in
      62.9% (44/70) and 51.4% (36/70), respectively. Twenty-six isolates were
      inconsistent with the conventional system and the new PCR with respect to
      morphology and serology. These findings suggested that the new PCR was more
      sensitive than Wang's PCR, and the new PCR in combination with morphology and
      serology is useful for P. pneumotropica identification.

PMID- 10067208
TI  - Opportunistic Pneumocystis carinii infection in red-bellied tamarins (Saguinus
      labiatus).
AB  - P. carinii infection in red-bellied tamarins (Saguinus labiatus), born and
      maintained in a laboratory breeding colony, was examined by histopathologic
      examination postmortem. P. carinii cysts were detected in 6 of 10 red-bellied
      tamarins examined, by using Grocott's, toluidine blue O and immunostaining with
      avidin-biotin complex using antisera for rat-, simian-, and human-P. carinii. The
      results obtained from the present studies imply that P. carinii may be an
      important pathogen in this species.

PMID- 10067209
TI  - Production of germfree mice by embryo transfer.
AB  - We applied the embryo transfer technique to germfree (GF) mouse production.
      Embryos harvested from superovulated mice were transferred aseptically, in a
      sterile environment, to the uterus of GF recipient females which had been mated
      with vasectomized GF males. One of the recipients became pregnant and delivered
      offspring. Sterility tests confirmed that the vasectomized males, newborns,
      recipient female mice, embryo-containing culture media, and the inside of the
      vinyl film isolator were germfree. These results suggest that the embryo transfer
      technique can be successfully applied to the production of GF mice.

PMID- 10067210
TI  - Linkage mapping of the rat Msh2 DNA mismatch repair gene on chromosome 6.

PMID- 10067211
TI  - [Congestive heart failure in infancy and childhood].
AB  - Congestive heart failure is the inability of the heart to provide a sufficient
      output at a sufficient arterial pressure for the metabolic needs of the organism.
      Having presented the physiologic mechanisms of the contraction of the heart and
      its regulatory mechanisms the different aspects of classification of heart
      failure and its neurohormonal modulation are described. The epidemiology of heart
      failure in childhood is largely unknown, the causes vary considerably, symptoms
      are age-dependent. Main diagnostic tools for etiologic clarification are
      echocardiography and chest-x-ray. Focus of therapy is to eliminate the causes,
      but general recommendations may not be forgotten. Medical treatment of acute
      severe heart failure is use of catecholamines, ino- and vasodilators in the
      intensive care unit. Therapy of chronic heart failure is performed with
      diuretics, digitalis and ACE-inhibitors. Their pharmacologic effect, therapeutic
      trials in adults and children and peculiarities of pharmacology and side effects
      in childhood are reported. Low dose beta-blockers are a new therapeutic strategy
      still not established in children.

PMID- 10067212
TI  - [Efficiency and risk of chest physiotherapy in the newborn--review of the
      literature].
AB  - Chest physiotherapy (CP) in the mechanically ventilated newborn infant belongs to
      standard treatment methods of neonatal intensive care units in many countries for
      more than twenty years. In the late seventies, some of the studies published were
      able to demonstrate a beneficial effect of CP on short time improvement of
      oxygenation in those newborns treated. Other trials dealt with the (patho)
      physiologic changes e.g. in cerebral perfusion following routine nursery
      procedures such as positioning, suctioning and CP. Recent studies have shown that
      the mechanically ventilated preterm infant is at risk to suffer intracranial
      bleeding or a "postnatal encephaloclastic porencephaly" due to routine CP.
      Prospective randomized trials with large patient numbers are needed to prove an
      effect of CP on shortening mechanical ventilation in the newborn. Meanwhile CP
      should not be administered on a routine basis especially not in the preterm
      infant, but only after assessment of the individual risk-benefit-ratio.

PMID- 10067213
TI  - [The congenital dislocation of the hip joint in ultrasound examination-
      frequency, diagnosis and treatment].
AB  - BACKGROUND: A real congenital dislocation of the hip joint is very rare. Because
      of the severeness of the disease an immediate diagnosis and begin of treatment is
      required. PATIENTS: Between 1984 and 1995 clinical and sonographic screening
      examinations at 4177 newborns were performed at our hospital. METHODS: We
      analyzed our patients retrospectively and found out all cases of congenital
      dislocation of the hip joint. All these cases were classified and the results of
      treatment were determined. The clinical success of our strategy of treatment was
      described. RESULTS: Among the 4177 observed newborns 39 cases of congenital
      dislocation of the hip joint in 27 children were found. We diagnosed the hip type
      IIIa, IIIb and IV according to Graf in 28.2 and 9 cases respectively. After 12
      month a complete healing rate of 95 percent was exhibited with the functional
      management strategy. Five percent of the affected joints showed a residual
      dysplasia. The rate of residual dysplasias was 2.5%. CONCLUSIONS: The good
      prognosis after our early treatment strategy severe congenital dislocation of the
      hip joint underlines the use of earliest therapy together with a hip screening
      program.

PMID- 10067214
TI  - [Standardized sonographic investigation of the lumbar spine in 247 newborns].
AB  - Open dysraphism is generally known before birth due to prenatal screening but
      occult spinal malformation often remains unrecognized. Nevertheless, newborns
      with occult dysraphism could be easily diagnosed by ultrasound, which might be
      performed additionally to the neonatal screening of the hips. Early surgical
      treatment or close neuropediatric follow-ups could be administered as a
      consequence. As part of a prospective study-design, we screened the spinal cord
      of 247 newborns by ultrasound. Parents were interviewed about a positive family
      history, a folate intake during pregnancy, amniocentesis or chorionbiopsy.
      Clinically, cutaneous stigmata usually associated with occult spinal dysraphism
      were evaluated. An orthopedic and pediatric examination followed. The sonographic
      investigation was done in prone position using a newly designed positioning
      device. The sonographic examination was performed within 5 minutes and
      longitudinal and transversal pictures were taken for documentation. In all of the
      247 examined newborns we were able to visualize the cartilageous structures of
      the spinal cord and the dural sack detailly. Dependent on the position of the
      newborn, variations of the width of the dural sack could be noted. Thus a newly
      designed positioning device helped to standardize the examination situation. We
      did not find any pathological changes of the spinal cord. Nevertheless
      ultrasonography provides a useful diagnostic tool in investigating the newborn
      where occult spinal dysraphism is expected.

PMID- 10067215
TI  - [Pyogenic sacroiliitis in children].
AB  - Pyogenic sacroiliitis is a rarely occurring disease. In recent years more reports
      have been published about this topic. We report on a case of infectious
      sacroiliitis in a young female patient. The multivarious clinical symptoms, the
      problems of diagnosis, differential diagnosis, treatment and prognosis of this
      disease will be described.

PMID- 10067216
TI  - Screening of patients with Turner syndrome for "hidden" Y-mosaicism.
AB  - The presence of Y-chromosomal sequences in the cells of patients with Turner
      Syndrome (TS) is a risk factor for the development of gonadal tumors. Therefore
      and since demonstration of Y-material usually results in prophylactic gonadectomy
      optimal sensitivity and specificity of the diagnosis have to be attempted. We
      wanted to evaluate the diagnostic potential of cytogenetic investigations as
      routinely employed in TS. In the most comprehensive study published so far we
      screened 208 TS patients for the presence of Y-chromosomal sequences by
      polymerase chain reaction (PCR) specific for eight different loci along the Y
      chromosome. Six patients (3%) without cytogenetic evidence of Y-chromosome were
      found to be Y-positive. Among 12 cases with marker chromosomes two more Y
      chromosomal fragments were identified. Thus, PCR-screening for Y-specific
      sequences was shown to be a valuable tool in the clinical management of Turner
      patients.

PMID- 10067217
TI  - [Trisomy 4p as result of a maternal translocation t(4;8)(q11;p23)].
AB  - We report on a 21 month old boy with congenital anomalies and a trisomy of the
      short arm of chromosome 4 as result of a maternal translocation 4/8 with meiotic
      3:1 segregation. Karyotype/phenotype correlation is compared with other reported
      cases and discussed in a context of nearly pure trisomy 4p.

PMID- 10067218
TI  - [Propofol for sedation in pediatric magnetic resonance imaging investigations].
AB  - BACKGROUND: Magnetic Resonance Imaging requires immobilisation of the patients
      without excitement due to acoustic irritation. During childhood this is hardly to
      guarantee without anaesthesia or sedation. The problem is the magnetic field
      strength, which interferes with the monitoring devices and the anaesthesia
      machines interrupting the function and can produce thermal injury, but
      additionally the tools will cause image degradation. PATIENT AND METHOD: MR
      Imaging was done in 46 children with a mean age of 50.9 months (0.06 to 129) in a
      sedation with propofol during spontaneous breathing. The induction dose of
      propofol was 3.0 mg/kg bodyweight and the repetition dose was 1.0 mg/kg. During
      the radiological examination and the time of emergence the children were
      monitored with a MRI-compatible fiberoptic pulseoximeter (NONIN), a capnography
      by naso-pharyngeal canula (OHMEDA) and a noninvasive blood pressure oscillometer
      (CRITICON). The monitors were located outside the 0.5 Tesla area and were
      connected to the patient via extension tubing. Additionally there was a clinical
      observation by a present anaesthesiologist. RESULTS: In all children the
      investigation has been realized without any problem. Haemodynamics, ventilation
      and oxygenation have been in a normal range. Only 2 of the 186 sequences had to
      be repeated. After a mean time of investigation of 29 minutes (10 to 55) the
      emergence time until purposeful reaction was 7.7 minutes (5 to 20) and until full
      orientation was 13.4 minutes (5 to 30). CONCLUSIONS: This regime of sedation for
      children undergoing Magnetic Resonance Imaging is safe and suitable independent
      of age: there is a good control of vital functions, a minimum of side effects and
      a fine recovery characteristic with short times of emergence.

PMID- 10067219
TI  - [Factitious skin lesions as an expression of a family crisis].
AB  - The factitious disorder is a deliberately induced, hidden self-mutilation based
      on a psychic conflict. We present a previously healthy nine-year old girl with
      initially obscure symmetric skin lesions. Family history, psychological
      exploration, special tests like pictural expression and scenial exhibition
      revealed the child's fear of a divorce of her parents and her own identity
      problem. These examinations aroused the suspicion that the girl could only
      express her conflict of ambivalence by self-injury behavior in the meaning of
      artificial disease. Guided by this impression, an intensive conversation with
      both parents was undertaken, focussing the familiar crisis. Afterwards, the skin
      lesions disappeared the girl admitted the self-mutilation. A family therapy was
      initiated.

PMID- 10067220
TI  - Techniques for MR imaging of joints in sports medicine.
AB  - Technical advances in MR imaging of sports-related bone and joint derangement
      have improved our ability to evaluate these problems. This article discusses
      current utilization of MR imaging, advances in local coils, pulse sequences and
      parameters, and reviews current aspects and indications for MR arthrography.

PMID- 10067221
TI  - MR imaging of rotator interval, long biceps, and associated injuries in the
      overhead-throwing athlete.
AB  - The rotator interval between supraspinatus and subscapularis is proving to be an
      important anatomic and functional region of the shoulder. Appreciation of the
      anatomic structures, functional importance, and mechanisms of injury are
      invaluable in appropriate assessment, both by physical examination and diagnostic
      MR imaging. The long biceps tendon; the superior labrum and labral-biceps anchor;
      the coracohumeral ligament merging with the rotator interval capsule and the
      superior glenohumeral ligament; the ligamentous reflection pulley for the long
      biceps tendon at the far lateral margin of the interval extending to the lesser
      tuberosity and proximal bicipital groove, bounded by the distal superior margin
      of the subscapularis and anterior margin of the supraspinatus tendons; and the
      transverse humeral ligament extending between the lesser and greater tuberosities
      along the proximal bicipital groove all are intimately associated in this region
      and may be injured together. Understanding of the anatomy and function of the
      rotator interval continues to evolve. Rotator interval injury may be better
      understood as a complex or spectrum rather than an isolated lesion. When any one
      of the spectrum of associated injuries is suspected or found, all of the other
      possible associated injuries should be considered and evaluated, both on clinical
      and MR imaging evaluations.

PMID- 10067222
TI  - MR imaging of the thrower's shoulder. Internal impingement, latissimus
      dorsi/subscapularis strains, and related injuries.
AB  - In conclusion, internal impingement apparently occurs in nearly all patients and
      is demonstrable on MR imaging. Pathologic changes associated with internal
      impingement seem to develop with repetitive placement of the arm into a position
      of extreme external rotation and abduction. Findings may include lesions of the
      posterior superior labrum, undersurface irritation, or tearing of the
      supraspinatus-infraspinatus junction near the attachment site and cystic changes
      of the posterior superior glenoid and posterior lateral greater tuberosity. There
      is no evidence for a particular sequence of pathologic changes. Instability may
      be associated with but does not appear to be a prerequisite for the development
      of the pathologic lesions of internal impingement.

PMID- 10067223
TI  - MR imaging of sports injuries of the elbow.
AB  - Recent clinical experience has shown MR imaging to provide useful information in
      detecting, assessing, and characterizing sports-related disorders of the elbow.
      This article discusses features of MR imaging, including noninvasivness; accurate
      depiction of structures (muscles, ligaments, and tendons), and presence and
      extent of bone and soft tissue pathology; and visualization (nerves, bone marrow,
      and hyaline cartilage). The article also reviews ongoing improvements in surface
      coil design, and newer pulse sequences resulting in MR images that are higher in
      quality and available more quickly.

PMID- 10067224
TI  - Role of MR imaging in the management of "skier's thumb" injuries.
AB  - "Skier's thumb" is an acute rupture of the ulnar collateral ligament (UCL) of the
      metacarpophalangeal (MCP) joint of the thumb. As the method of choice in
      evaluating soft tissue injuries, MR imaging is useful in evaluating UCL injuries.
      This article reviews current concepts regarding the rupture of the UCL, including
      a study of 34 UCL injuries in which MR imaging was used as the main diagnostic
      tool. When correlated with surgical findings, MR imaging resulted in identifying
      UCL tears with 96% sensitivity and 95% specificity.

PMID- 10067225
TI  - MR imaging of the spine in sports injuries.
AB  - MR imaging has afforded an ability to better visualize and characterize a whole
      host of spine abnormalities encountered in the athletic population. It remains
      the mainstay in the noninvasive diagnosis of most soft-tissue abnormalities
      occurring within and about the spine. Its role in the evaluation of central
      spinal stenosis, the central spinal canal, and the spinal cord is unsurpassed by
      other noninvasive imaging modalities. In the setting of underlying fractures, it
      is complementary to CT, particularly with respect to evaluating concomitant soft
      tissue and ligamentous abnormalities. With its ability to image edema and
      reactive marrow changes, it is useful in the evaluation of osseous stress changes
      that may occur in the athletic population.

PMID- 10067226
TI  - MR imaging of sports injuries of the hip.
AB  - While MR imaging studies of the hip have been directed routinely toward the
      diagnosis of atraumatic osteonecrosis (ON), interest has increased in the use of
      MR imaging to diagnose other disorders of the hip and surrounding soft tissues,
      especially in athletic injuries. In addition to reviewing MR imaging technical
      considerations and image appearance, this article discusses applications of MR
      imaging to diagnosing pelvic and hip fractures, muscle contusion and strain,
      tendon injuries, acetabular labral tears, bursitis, and osteitis pubis and
      chronic symphyseal injury.

PMID- 10067227
TI  - MR imaging of knee anterior cruciate ligament and associated injuries in skiers.
AB  - Tears of the ACL have become widespread in the skiing population. Understanding
      of the mechanisms and patterns of associated injury of such ACL tears has
      benefited from and contributed greatly to clinical and imaging evaluation and
      management. MR imaging of the injured knee has become the gold standard
      comprehensive imaging examination for evaluating the ACL tear and associated soft
      tissue and osseous injuries and assisting the treating physician in planning
      management, as the isolated ACL tear has proven to be the exception rather than
      the rule in skiing knee injuries.

PMID- 10067228
TI  - MR imaging in sports injuries of the foot and ankle.
AB  - MR imaging has become the diagnostic modality of choice for the evaluation of
      traumatic ligamentous and tendinous injures of the foot and ankle, occult bony
      trauma, and osteochondral lesions of the talus. This article reviews the current
      applications of MR imaging for the evaluation of sports-related injuries of the
      foot and ankle, including fractures, sprains, tendon injuries, and heel pain.

PMID- 10067229
TI  - MR imaging of stress reactions, muscle injuries, and other overuse injuries in
      runners.
AB  - Running-related injuries are increasingly common, and most often due to overuse.
      This article briefly discusses the biomechanics of running, and a general review
      of stress lesions of bone; site-specific reviews of bony stress lesions and other
      running-related soft tissue injuries; and associated MR imaging findings.

PMID- 10067230
TI  - Role of MR imaging in the management of injuries in professional football
      players.
AB  - This article discusses the effectiveness of MR imaging in evaluating the injuries
      of both upper and lower extremities in the professional football player. Topics
      include bone, joint and soft tissue disorders, and injuries resulting from
      overuse or trauma of the shoulder, elbow, forearm, and wrist; the pelvis and hip,
      lower extremity muscle and tendon, knee, and ankle.

PMID- 10067231
TI  - Role of MR imaging in sports medicine research. Basic science and clinical
      research studies.
AB  - The advent and advancement of MR imaging have provided an entire new dimension
      for medical imaging. MR imaging has been especially useful because of its
      capacity to image nonmineralized tissues with a very high degree of resolution.
      Although modalities such as ultrasound and scintigraphy have proven useful for
      specific purposes, it is MR imaging that has the most utility and capabilities,
      especially in the area of sports-induced injuries. The technology associated with
      MR imaging has expanded greatly, and it continues to evolve at a rapid pace. The
      result has been an ever-increasing diagnostic capability that has become more
      economic with time. As described previously, MR imaging is gaining importance in
      the area of comparative medicine for animal athletes as well. It is also
      interesting to note that MR imaging now has a greater potential for monitoring
      physiological and biochemical changes as well as anatomic ones. Some newer MR
      units actually include physiologic data acquisition components. Consequently, new
      bioassays and nondestructive tissue tests can be performed to further understand
      the molecular biology and ongoing cellular processes in any given condition.
      Coupled with MR spectroscopy, the enhanced MR techniques should continue to
      contribute to the overall information that will be integrated into the training
      and rehabilitation of patients with sports-induced inflammation and injuries. The
      authors support and encourage ongoing efforts in the area of MR imaging research,
      both basic science and clinical studies.

PMID- 10067232
TI  - [Young children's representational theory of mind in understanding masked facial
      expression].
AB  - In this study, development of young children's understandings of masked facial
      expression was examined from the perspective of the development of "theory of
      mind". In Experiment 1, short stories in which one character masks facial
      expressions to make another character have false beliefs were presented to 3-, 4
      , and 6-year-old. They were asked questions to assess their judgements on various
      mental states (desire, belief, and intention) of story characters. And, to assess
      children's "representational theory of mind", they performed a "Smaties Task".
      The results showed that recognition of masked facial expression was developed
      from 3 to 4 years. Scores on "Smaties Task" was also improved during the same
      period. An additional analysis showed that the major determinant of to determine
      the understanding of masked facial expression was not the age but the possession
      of "representational theory of mind". In Experiment 2 more sophisticated but
      similar type of procedures were presented to 3- and 4-year-old children. Results
      replicated the results in Experiment 1 and the understanding of the intention of
      characters was also found to develop from 3 to 4 years.

PMID- 10067233
TI  - [A study on the response selection and inhibition in a cognitive conflict task
      using event-related potentials].
AB  - This study examined the hypothesis (Eriksen & Schultz, 1979) that a subject
      checks whether a prepared response is correct or not in the Eriksen and Eriksen
      (1974) cognitive conflict task, using event-related potentials (ERPs). Fourteen
      right-handed subjects were required to respond selectively to a central target
      letter flanked with compatible (e.g., HHHHHHH) or incompatible (e.g., SSSHSSS)
      noise letters, or not to respond to asterisks (*******). The results showed that
      the lateralized readiness potential indicating an incorrect preparation and the
      NO-GO potential reflecting a response inhibition emerged for incompatible
      stimuli. These findings indicate that a prepared response was recognized as
      erroneous, and was inhibited. Therefore, it is suggested that the check operation
      functioned in the cognitive conflict task. Furthermore, the result that the NO-GO
      potential latency for incompatible stimuli was longer than that for NO-GO stimuli
      suggests that the timing of NO-GO decision and response inhibition by the check
      operation influenced the NO-GO potential latency.

PMID- 10067234
TI  - [Collage therapy and an analysis of production process in collage work].
AB  - An application of collage as an art form has been made in clinical psychology,
      and has been established as collage therapy. This paper attempted to answer the
      following questions: What kind of behavior people show during production of
      collage work; how the production behavior differs from person to person; what
      causes the behavior differences. The framework of creative problem solving and
      behavior analysis technique with VTR were used, and behavior characteristics of
      mentally retarded subjects (N = 20) were compared with non-retarded adults (N =
      20). Results revealed three behavior patterns: Whole linear type ([SEAF]n),
      partially repeated linear type ([SE]n and [AF]m), and circuit type ([SEA]n and
      [AF]m) from the analysis of transition probability of four fundamental action
      elements (search [S], extraction [E], arrangement [A] and fixation [F]) of
      collage work production. The difference in the production process of each subject
      may be attributed to the difference in proportions of the three behavior
      patterns. The proportion difference in turn appeared to reflect that on the
      global-local dimension in the work production plan.

PMID- 10067235
TI  - [Effects of PAC (personal attitude construct) analysis in counseling].
AB  - The aim of the present study is to prove that the use of PAC Analysis will
      enhance and facilitate counseling effects. Eleven functions were hypothetically
      presented: (1a) Intake Facilitation Function, (1b) Self-Disclosure Facilitation
      Function, (1c) Trust Formation Function, (1d) Dialogue Development Function, (2a)
      Mutual Understanding Function, (2b) Clarification Function, (2c) Self
      Understanding Facilitation Function, (2d) Counselor's Awareness Function, (3a)
      Descriptive Documentation Function, (3b) Practical Explanation Function, and (3c)
      Evaluation-Assessment Function. By examining two case studies of international
      students' counseling process, these functions were analyzed. Results showed that
      all the functions were confirmed. Introducing PAC Analysis into counseling is
      proved to be effective in the direct intermental function field in counseling
      process (1a to 1d), the intramental function field between a client and a
      counselor (2a to 2d), and the indirect intermental function field including
      description, explanation, and assessment (3a to 3c). It is discussed that PAC
      Analysis is expected to take an important role in counseling in general.

PMID- 10067236
TI  - [Effects of fimbria-fornix lesion on the temporal discrimination revealed by peak
      interval procedure in rats].
AB  - When temporal discrimination is examined by a peak interval (PI) procedure in
      rats, a shortening of peak time is induced by the fimbria-fornix (FF) lesion. The
      aim of this research is to investigate the extent of peak time shortening induced
      by FF lesion and the acquisition process of temporal discrimination. In FF
      lesioned rats, the peak time was very short (about 13 sec) in earlier phase, then
      became longer as the training progressed and reached a steady level, which was
      approximately 20% shorter than control rats. These results suggest that the "non
      timing process" is involved in addition to the "timing process" in FF lesioned
      rats.

PMID- 10067237
TI  - [Effects of body control and attention on body sway induced by a tilting room].
AB  - The purpose of this study was to examine the effects of body control and
      attention on body sway that was induced by a "tilting room". With an initial
      instruction, 18 subjects were divided into two groups: target and body attention
      groups, and then stood on a stabilometer in a room that tilted forwardly. Body
      sway that was induced by the tilting room was measured with the stabilometer.
      During the training session, subjects received Dohsa training (Naruse, 1973) in
      order to control their body movement. Analyses indicated the following: (1)
      Subjects swayed in the same direction as tilting of the room; (2) No difference
      in the body sway was found for the two groups before training; and (3) After
      training, subjects increased the controllable area on the stabilometer and
      learned to use their bodily sensation better. Subjects in the target attention
      group had a greater increase in body sway than the other group. These results
      suggest that adult flexibility appeared in an ecological situation where
      conflicting information was received through visual and bodily sensation.

PMID- 10067238
TI  - [Prospective memory and its theoretical considerations].
AB  - Prospective memory involves memory for future intentions in our everyday lives
      and it is one of the hot topics in current memory research. We reexamined what is
      prospective memory and discussed how intentions had been conceived of in the
      history of psychology. We emphasize the necessity of classifying a form of
      remembering intentions into the self-initiated existence-remembrance and its
      content-remembrance. Many studies on prospective memory in recent decades were
      reviewed with respect to the following perspectives: (1) how intentions are
      recollected, (2) what is remembering intentions based on, (3) how we attempt to
      avoid forgetting to do things, and (4) what is neuropsychological mechanism of
      remembering intentions. Requirements for experimental research on prospective
      memory are summarized and future directions are discussed.

PMID- 10067239
TI  - [Factors associated with progression of kidney diseases and principal
      possibilities of affecting them].

PMID- 10067240
TI  - [Variability of the hypolipidemic action of simvastatin and fluvastatin in
      patients with primary hyperlipoproteinemia].
AB  - AIM: To reveal the metabolic parameters of lipoproteins (L), which determine the
      benefits of hypolipidemic effects of simvastatin (S) and fluvastatin (F); to
      trace changes in the activity of lecithin-cholesterol acyltransferase (LCA) and
      cholesterol (C) ester transfer (CET) from high density lipoproteins to very low
      density lipoproteins (VLDL) and low density lipoproteins (LDL) and the levels of
      apoE in the blood and in some L classes during therapy with the above drugs.
      MATERIALS AND METHODS: Thirty six patients took S, 10 mg/day, and 25 received F,
      20 mg/day, for 3 months. The levels of lipids were measured by enzyme assays,
      apoprotein (apo) was determined by immunoturbidimetry and immunodiffusion.
      RESULTS: The hypocholesterolemic and hypotriglyceridemic effect of S (19.6 and
      25.5, respectively) and F (19.0 and 30.5%) were similar. With S, the reduction in
      the blood levels of C and LDL C positively correlated with the baseline apoE
      levels. With F, it did with C and LDL C before treatment. Lower blood apoE was
      found with S and F and lower HDL apoE/(VLDL + LDL) ratio was detected only with
      F. F treatment significantly lowered the activity of CET and LCA; before and
      after S treatment, they did not differ significantly. CONCLUSION: Analyzing the
      relationship between the benefits of the hypolipidemic effect and the baseline
      parameters of L metabolism indicates that the changes in serum C, LDL C and HDL C
      are due to the composition of HDL particles and the distribution of apoE among
      different L classes in the patient to a greater degree.

PMID- 10067241
TI  - [Relationship of vascular reactivity to blood lipid spectrum and lipid
      peroxidation in unstable angina].
AB  - AIM: To examine the relationship between the vascular response of the
      microcirculatory bed to vasoactive agents and lipid peroxidation (LPO) and
      antioxidative defense in patients with unstable angina pectoris. MATERIALS AND
      METHODS: Thirty male patients (mean age 58.0 +/- 2.4 years) were examined. The
      patients were divided into 2 groups: 1) those with high alpha-cholesterolemia
      alone and 2) those with high alpha-cholesterolemia concurrent with
      hyperglyceridemia and elevated total cholesterol levels. Photoplethysmographic
      determination was used to evaluate vascular responses to norepinephrine
      (vasopressor function) and histamine (vasodilating function), the blood levels of
      cortisol, LPO products, antioxidative protection components, histamine, and
      serotonin. RESULTS: Vascular dilating function was found to be most pronounced in
      Group 1. Moreover, Group 1 patients had a significant depression of the
      antioxidative defense system and the highest blood levels of cortisol, and
      serotonin. The levels of LPO products did not differ significantly in both groups
      though they were significantly higher than those in healthy individuals.
      CONCLUSION: Impairment in the antioxidant system and in coordination of
      vasodilating function to histamine stimulation are typical of patients with
      unstable angina.

PMID- 10067242
TI  - [Features of individual pain sensitivity of patients with ischemic heart disease
      during different variants of bicycle ergometry test].
AB  - AIM: To assess the significance of individual pain sensitivity in the development
      of painful and painless episodes of acute myocardial ischemia. MATERIALS AND
      METHODS: Bicycle ergometry test was carried out in 50 patients aged 35-65 years
      with angina of effort, functional classes II-III. Before bicycle ergometry,
      tactile and pain sensitivity thresholds and duration of pain tolerance were
      assessed by SSM-01 sensometer. RESULTS: Twenty-seven patients showed painful
      reaction to exercise; 40% of them had a low threshold of pain and 81% poorly
      tolerated pain. In 11 patients who complained of pain before ECG showed
      myocardial ischemia, these values were 64 and 91%, respectively. All of 9
      patients with painless myocardial ischemia had a high threshold of pain, and 44%
      of them poorly tolerated pain. CONCLUSION: The data indicate significance of
      individual pain sensitivity in the development of painless episodes of acute
      myocardial ischemia.

PMID- 10067243
TI  - [Effects of fenigidin treatment regimen on the state of peripheral hemodynamics
      of patients with stable effort angina pectoris and postinfarction
      cardiosclerosis].
AB  - AIM: To examine the impact of fenigidin treatment regimen on peripheral
      hemodynamics in patients with stable angina pectoris of effort and postinfarction
      cardiosclerosis without signs of heart failure. MATERIALS AND METHODS: Thirty two
      patients with functional classes II and III stable angina of effort and 32 with
      postinfarction cardiosclerosis without signs of heart failure were examined.
      RESULTS: Monotherapy with fenigidin, 30-40 mg/day in patients with stable angina
      pectoris of effort and in those with postinfarction cardiosclerosis lowered
      systolic and mean blood pressures, total and specific peripheral vascular
      resistance, venous tone and increased additional venous volume and maximum vein
      emptying rate in the upper and lower extremities. Fenigidin therapy caused no
      side effects. CONCLUSION: Fenigidin monotherapy improves hemodynamic parameters
      in stable angina pectoris of effort and postinfarction cardiosclerosis without
      obvious signs of heart failure and causes no side effects when the drug is used
      in a dose of 30-40 mg/day for 3 weeks.

PMID- 10067244
TI  - [Association of the metabolic syndrome components in patients with arterial
      hypertension and their relationship with dyslipidemia].
AB  - AIM: To detect the correlation between complete metabolic syndrome (MS) and
      combinations of arterial hypertension (AP) with abdominal obesity (AO),
      hyperlipidemia (HLP), and both without disorders in glucose tolerance. MATERIALS
      AND METHODS: 122 men aged 35-66 years were examined, in whom AP was diagnosed 4-6
      years before. The following criteria were used for detecting MS components: AP
      was diagnosed at diastolic AP of at least 90 mm Hg or systolic AP of 140 mm Hg;
      HLP was confirmed at total cholesterol (CS) level of at least 5.2 mmol/liter
      and/or triglyceride (TG) level of at least 2.3 mmol/liter; AO was diagnosed at
      body weight index of at least 26 kg/m2 and the ratio of waist/hip circumferences
      more than 0.90. Poor glucose tolerance was diagnosed at glucose level in
      capillary blood 120 mg/dl and higher, but no more than 180 mg/dl 2 h after 75 g
      glucose loading, if glucose level after an overnight fasting was no higher than
      120 mg/dl. RESULTS: The majority of patients (39.3%) had combinations of AP with
      AO and HLP; complete MS was diagnosed in 21%. Isolated AP was found in only 8.2%
      of examinees. Dyslipidemia in the presence of MS and in combinations of AP with
      AO and HLP was characterized by increased levels of TG and total CS and decreased
      content of CS and high-density lipoproteins, which was associated with basal
      hyperinsulinemia. CONCLUSION: MS alone and clusters of AP, AO, and HLP
      characterized by insulin resistance, accelerate the development of cardiovascular
      diseases associated with atherosclerosis.

PMID- 10067245
TI  - [Role of cell membrane abnormalities in the etiology of arterial hypertension].
AB  - AIM: To study the role of cell membrane disorders in the formation of arterial
      hypertension under conditions of Extreme North. MATERIALS AND METHODS: A total of
      128 men aged 20-48 years with essential hypertension (EH) were examined. All of
      them worked in the duty regimen at the Extreme North. Control group consisted of
      EH patients living in the temperate climatic zone. Central and peripheral
      hemodynamic parameters and cell membrane characteristics were studied: activities
      of transmembrane ion transport enzymes, intracellular electrolytes sodium and
      calcium, lipid peroxides (LPO), antioxidant defense values in erythrocyte
      membranes, plasma and cell membrane cholesterol. RESULTS: Activation of LPO
      processes and decreased antioxidant defense in both groups modified the lipid
      spectrum of cell membranes. The levels of intracellular calcium and sodium were
      increased, activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase decreased; total
      peripheral vascular resistance and left ventricular myocardium were progressively
      increasing. CONCLUSION: Membrane-destabilizing processes and hemodynamic shifts
      were more expressed in subjects with arterial hypertension working in the duty
      regimen.

PMID- 10067246
TI  - [Substantiation of patients' length stay in hospital after acute myocardial
      infarct].
AB  - AIM: To study and validate the duration of optimal hospital stay for
      postmyocardial infarction patients and to specify indications for their
      discharge. MATERIALS AND METHODS: The trial enrolled 187 patients with large- and
      small-focal acute myocardial infarction. The patients were divided into two
      groups by different speed of activization and hospital stay. RESULTS: There were
      no significant differences between the groups with different duration of hospital
      stay by working ability and invalidism. Temporary disability in patients who have
      undergone standard rehabilitation was longer than in patients on the shorter
      program rehabilitation. Performance of exercise tests on day 14 distinguished
      patients with a favourable long-term prognosis who were candidates for shorter
      rehabilitation program. CONCLUSION: The program of quicker rehabilitation (a two
      times decrease in the hospital stay) can be applied to patients with
      uncomplicated myocardial infarction without damage to their health.

PMID- 10067247
TI  - [Phenomenon of preoperative stress in patients with ischemic heart disease.
      Assessment of its clinical and prognostic significance].
AB  - AIM: To assess preoperative stress in patients with ischemic heart disease (IHD)
      and its influence on the course of early intraoperative period. MATERIALS AND
      METHODS: 79 patients scheduled for aortocoronary bypass operation were studied to
      assess the phenomenon of preoperative psychoemotional stress (clinical
      characteristics, personal anxiety, humoral and vegetative regulation. RESULTS: 24
      hours before operation IHD patients became anxious, coronary insufficiency and
      arrhythmia aggravated as shown by Holter ECG monitoring. Initial insufficiency of
      the antioxidant system, disturbances of the platelet-vascular hemostasis,
      hyperlipidemia and dyslipoproteinemia enhanced. Preoperative changes due to
      stress reaction affected the course of early intraoperative period. CONCLUSION:
      It is necessary to apply individual schemes of stress-limiting preoperative
      preparation in IHD patients.

PMID- 10067248
TI  - [Early and late (during 3 years) results of coronary bypass operation in patients
      with ischemic heart disease with moderate dyslipoproteinemia].
AB  - AIM: The study of efficacy of rehabilitation and clinical-instrumental
      characteristics of coronary failure in patients with ischemic heart disease (IHD)
      of high functional classes and moderate dyslipoproteinemia early (1.6 months) and
      late (1 and 3 years) after coronary by-pass operation. MATERIALS AND METHODS: The
      examination covered 119 males with IHD (mean age 51.8 +/- 6.9 years) 1.6 months
      and 3 years after coronary by-pass operation. Lipid spectrum of blood plasma,
      frequency of anginal attacks, 24-h nitroglycerin requirement, results of bicycle
      exercise and loading myocardial scintigraphy were assessed. The patients were
      divided into two groups. In 82 patients of group 1 total cholesterol ranged
      within 3 years after the surgery from 5.2 to 6.5 mmol/l, 37 patients of group 2
      had no lipid disorders. RESULTS: Within 12 months after direct myocardial
      revascularization, the groups had similar clinical-instrumental characteristics.
      3 years after the operation, patients of group 1 exhibited a rise in anginal
      attacks frequency, nitroglycerin requirement, size of unstable perfusion defects
      by 84.6, 88.8 and 26.4%, respectively. Exercise tolerance diminished by 18.7%.
      CONCLUSION: Moderate defects in lipid metabolism influence progression of
      coronary failure. This becomes especially pronounced within 3 years after
      coronary by-pass operation.

PMID- 10067249
TI  - [Antiphospholipid antibodies in hypertension].

PMID- 10067250
TI  - [Hypertrophic cardiomyopathy in a female patient with systemic lupus
      erythematosus].

PMID- 10067251
TI  - [Epidemiology of bronchial asthma in a large industrial region].
AB  - AIM: To estimate the prevalence of bronchial asthma (BA) basing on the complex of
      the disease symptoms within the last year associated with bronchial obstruction
      (BO) and bronchial hyperreactivity (BHR). MATERIALS AND METHODS: A questionnaire
      survey (IUATLD) has covered 1572 individuals (mean age 40.1 +/- 0.3 years, 837
      females). The responders were divided into 3 age groups. BO and BHR were
      examined, concentration of air pollutants NO2, SO2, CO were measured. RESULTS:
      The most typical BA symptoms were defined in males and females in different age
      groups. The relationship between frequency of BA symptoms on concentration of air
      pollutants was determined. BO and BHR were found in 13.3% of the respondents.
      CONCLUSION: Prevalence of BA in a large industrial region is 16.4% (17.5% in
      males and 14.0% in females).

PMID- 10067252
TI  - [Treatment of bronchial asthma by the Su-Jok therapy method].
AB  - AIM: To evaluate the influence of su-jok therapy (one of the methods of
      alternative medicine) in combination with chemotherapy on the course of bronchial
      asthma. MATERIALS AND METHODS: 68 patients have undergone su-jok therapy in
      combination with drug treatment in accordance with international asthma
      consensus. Control group of 44 patients received only chemotherapy. The response
      was assessed by: quantitative indices of asthma course, FEV1, FEF 25, 75, 50,
      PEF, demand of beta2-agonists, long-term outcomes. RESULTS: The efficiency
      coefficient made up 2.64 in patients versus 1.48 in controls. Demand of beta2
      agonists reduced 4 times versus 1.6 times, respectively. The degree of
      improvement of bronchial permeability at the level of distal bronchus was 2 times
      higher in the study group. Other functional parameters were not significantly
      different. The period free of exacerbations with hospital care was 1.7 times
      longer in patients on su-jok therapy. CONCLUSION: The su-jok therapy adjuvant to
      chemotherapy is highly effective.

PMID- 10067253
TI  - [Delayed-type hypersensitivity in insulin-dependent diabetes mellitus and effects
      of short-action insulins produced by different pharmaceutical firms].
AB  - AIM: The study of activity of T-effector lymphocytes of delayed-type
      hypersensitivity (DTH) in insulin-dependent diabetes (IDD) and effects of short
      action insulins produced by different pharmaceutical firms. MATERIALS AND
      METHODS: 79 IDD patients aged 3-48 entered the study. RESULTS: T-effector
      lymphocytes activity in DTH patients was abnormal: leukocytes migration was
      enhanced due to inhibited production of the inhibiting factor. Effector function
      was subnormal. Short-acting insulins promoted normalization of the above indices.
      The insulins of different producers is individual in efficacy for each patient.
      CONCLUSION: In vitro tests are necessary for each patient to determine insulin
      activity before insulin therapy.

PMID- 10067254
TI  - [Effects of tanakan on blood lipid peroxidation and platelet aggregation
      properties in patients with insulin-dependent diabetes mellitus].
AB  - AIM: To elucidate tanakan effects on lipid peroxidation (LPO) products in blood
      serum, red cell and platelet membranes of patients with insulin-dependent
      diabetes mellitus (IDDM) with and without vascular complications. MATERIALS AND
      METHODS: Twenty-seven diabetics and 15 donors were examined. Platelet
      aggregation, malonic dialdehyde (MDA), hemoglobin (including glycosylated), blood
      total cholesterol and lipoproteins were measured routinely. RESULTS: Elevated
      levels of malonic dialdehyde (MDA) in the serum and red cell membrane in IDDM
      patients diminished in response to 6-week treatment with tanakan. Basal and
      induced MDA in platelets reduced, more noticeably in patients without angiopathy.
      Platelets resumed sensitivity to low-dose ristomycin. A 6-week course of tanakan
      failed to normalize platelet function completely. Moreover, platelets sensitivity
      to some inductors (ADP, adrenalin) enhanced, more noticeable in patients without
      angiopathy. CONCLUSION: Tanakan in IDDM shows properties of an effective
      antioxidant and return to normal LPO products level both in blood serum and red
      cell membrane. This eradicates a damaging action of free radical products in
      blood cells and endothelium. It is suggested that for normalization of platelet
      aggregation in IDDM a longer tanakan course is required or combined use of
      tanakan with other antithrombotic medicines of different mechanism of action may
      be effective.

PMID- 10067255
TI  - [Dynamics of the level and structure of mortality of Russia's population
      according to main classes of cause of death in the period 1985-1995 (an
      analytical review of official data)].

PMID- 10067256
TI  - [Immunological aspects of circulating immune complexes in kidney diseases in
      patients with chronic alcoholism].
AB  - AIM: Characterization of the content and features of circulating immune complexes
      (CIC) in chronic alcoholics with renal diseases. MATERIALS AND METHODS:
      Quantitative and qualitative characteristics of CIC, RNA and DNA levels in CIC
      were studied in 58 patients suffering from chronic alcoholism stage II. The
      patients had the history of 10 and more years of alcohol abuse, exhibited
      symptoms of chronic renal affection with clinical picture of chronic
      glomerulonephritis. RESULTS: Glomerulonephritis in chronic alcoholics was
      accompanied with higher CIC, CIC IgM and IgA levels compared to healthy subjects
      and non-alcoholics with glomerulonephritis. Alcoholics had also higher DNA and
      CIC DNA. CONCLUSION: Quantitative and qualitative assessment of CIC in chronic
      alcoholics with renal disease provide information valuable for the disease
      diagnosis and prognosis.

PMID- 10067257
TI  - [Neuralgia and zovirax treatment of patients with herpes zoster].
AB  - AIM: To estimate the occurrence of postherpetic neuralgia (PHN) arising after
      acute period of herpes zoster (HZ) and determination of zovirax efficiency in PHN
      prevention. MATERIALS AND METHODS: Of a total of 102 patients with HZ aged 17-89
      years, 20 patients aged 26-83 years were given zovirax. RESULTS: Acute pain
      syndrome in PHN was observed in more that one-third of HZ patients. Patients over
      60 years of age were more predisposed to PHN. Zovirax reduced the duration of
      acute rash and its healing, decreased the number of patients with zoster
      associated pain and PHN patients. CONCLUSION: Zovirax is effective and safe in
      preventing PHN in HZ patients.

PMID- 10067258
TI  - [Scientific validation of the use of efferent methods].

PMID- 10067259
TI  - [Heparin in the treatment of unstable angina. Can the decrease of the molecular
      size increase its effectiveness?].

PMID- 10067260
TI  - [Antiphospholipid syndrome: serological markers, diagnostic criteria, clinical
      manifestations, classification, prognosis].

PMID- 10067261
TI  - [Brufen on the eve of the 21st century].

PMID- 10067262
TI  - [The range of clinical use of current calcium antagonists].

PMID- 10067263
TI  - [Cardiorespiratory disorders in drug addiction].

PMID- 10067264
TI  - [Are there still indications for albumin?].

PMID- 10067265
TI  - Genetics and metabolism of lipoprotein(a) and their clinical implications (Part
      1).
AB  - The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a
      genetically determined risk factor for atherosclerotic vascular diseases.
      Numerous (including prospective) studies have described a correlation between
      elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral
      atherosclerosis. Lp(a) consists of a large LDL-like particle to which the
      specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on
      chromosome 6 and belongs to a gene family including the highly homologous
      plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the
      extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a
      size polymorphism. The size of the apo(a) isoform is inversely correlated with
      Lp(a) plasma concentrations, which are non-normally distributed in most
      populations. To a minor extent, apo(a) gene-independent effects also influence
      Lp(a) concentrations. These include diet, hormonal status and diseases like renal
      disease and familial hypercholesterolemia. The standardisation of Lp(a)
      quantification is still an unresolved problem due to the enormous particle
      heterogeneity of Lp(a) and homologies of other members of the gene family.
      Stability problems of Lp(a) as well as statistical pitfalls in studies with small
      group sizes have created conflicting results. The apo(a)/Lp(a) secretion from
      hepatocytes is regulated at various levels including postranslationally by apo(a)
      isoform-dependent prolonged retention in the endoplasmic reticulum. This
      mechanism can partly explain the inverse correlation between apo(a) size and
      plasma concentrations. According to numerous investigations, Lp(a) is assembled
      extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms
      of Lp(a) removal from plasma are only poorly understood. The human kidney seems
      to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism
      is rather unclear; several candidate receptors from the LDL-receptor gene family
      do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over
      controls in patients with renal diseases like nephrotic syndrome and end-stage
      renal disease. Following renal transplantation, Lp(a) concentrations decrease to
      values observed in controls matched for apo(a) type. Controversial data on Lp(a)
      in diabetes mellitus mainly result from insufficient sample sizes in numerous
      studies. Large studies and those including apo(a) phenotype analysis have come to
      the conclusion that Lp(a) levels are not or only moderately elevated in insulin
      dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated.
      Several rare disorders, such as LCAT and LPL deficiency, as well as liver
      diseases and abetalipoproteinemia are associated with low plasma levels or lack
      of Lp(a).

PMID- 10067266
TI  - LYS-plasminogen shortens the duration of local thrombolytic treatment of
      peripheral arterial occlusions--a randomized controlled trial.
AB  - Local thrombolytic treatment of peripheral arterial occlusions, which has been
      accepted as a therapeutic alternative to surgical treatment, is not always
      successful. One of the reasons for unsuccessful thrombolytic treatment might be a
      low concentration of plasminogen in the thrombus or insufficient activation of
      the thrombolytic system. Therefore the purpose of this study was to determine
      whether the success of local treatment of peripheral arterial occlusions of lower
      extremities with streptokinase could be improved by enriching the thrombus with
      exogenous plasminogen and furthermore, if the therapeutic success depends on a
      systemic fibrinolytic effect. In a prospective randomized study two groups of
      patients with acute and subacute arterial occlusions of the lower limbs (Stage
      III, IV) were treated with a continuous infusion of local low dose of
      streptokinase (SK). The first group (45 patients, mean age 73 years) was treated
      with SK only (3750 IU/hour) (SK group). While the patients in the second group
      (43 patients, mean age 72 years) received exogenous lys-plasminogen (7.5 mg)
      before application of SK in thrombi (SK-Plg group). The treatment was successful
      in 69% (31 out of 45 patients) of the SK group and in 77% (33 out of 43 patients)
      of the SK-Plg group. Although lysis of thrombi was observed more frequently in
      the SK-Plg group than in the SK-group, the clinical outcome was comparable
      between groups. In successfully treated patients from the SK-Plg group the
      duration of treatment was significantly shorter than in the SK group (33 +/- 8 hr
      vs. 53 +/- 11 hr, p < 0.01). A significant decrease of fibrinogen concentration
      as an indicator of activation of fibrinolysis was not observed in the majority of
      treated patients. On the other hand, in successfully treated patients of both
      groups, the following was observed: 24 hour after the beginning of treatment,
      euglobulin clot lysis times were shortened to half of baselines values, and the
      plasminogen concentration was also significantly reduced (to 55% of the baseline
      value). In unsuccessfully treated patients no significant changes in fibrinolytic
      parameters were observed. The results of our study indicated that enrichment of
      the thrombus with exogenous plasminogen does not significantly improve the
      percentage of successful recanalization of peripheral arteries with a local low
      dose of SK, but significantly shortens the duration of treatment up to
      reperfusion. The study also showed that in local thrombolysis for the treatment
      of arterial occlusion a certain degree of systemic activation of the fibrinolytic
      system is essential for successful dissolution of the thrombi.

PMID- 10067267
TI  - [Hypoplastic left-heart syndrome. Initial intensive care experiences with the
      Norwood operation in Vienna].
AB  - Palliative surgery of the hypoplastic left heart syndrome (HLHS), whereby both
      pulmonary and systemic circulation are restored, was first described by Norwood
      in 1983. Careful ventilatory and pharmacologic modulation of the ratio of
      pulmonary to systemic vascular resistance are a crucial part of pre-, peri- and
      postoperative management. We report our experience in 3 of 7 newborns with HLHS
      who underwent the Norwood operation. Hemodynamic and respiratory parameters were
      evaluated retrospectively in these patients and we analysed the influence of
      diagnostic and therapeutic interventions on the course of disease before and
      after operation. During prostaglandin therapy two of three patients required
      mechanical ventilation preoperatively because of pulmonary hyperperfusion.
      Decreased myocardial contractility, oliguria and increased pulmonary vascular
      resistance characterized the postoperative course. The management included a
      careful application of inotropic support when necessary, adaptation of the
      ventilatory setting in order to modulate pulmonary perfusion and, in addition,
      institution of peritoneal dialysis. One patient died from staphylococcus aureus
      and superinfection with respiratory syncytial virus on day 41 after the
      operation. Maintaining an optimal balance between pulmonary and systemic blood
      flow is an essential aspect of postoperative management. Serum lactate and
      central venous oxygen saturation are helpful parameters in monitoring therapeutic
      measures in these patients. We conclude from our preliminary experience, that the
      Norwood operation might be an alternative therapeutic approach for newborns with
      HLHS in whom heart transplantation is not possible.

PMID- 10067268
TI  - [An adult patient with phenylketonuria before and one year after reinstitution of
      diet therapy].
AB  - BACKGROUND: In phenylketonuria (PKU) a phenylalanine restricted diet during the
      first years of life can prevent the development of severe cognitive damage.
      OBJECTIVE: Could neuropsychological or neurological changes occur in a 20-year
      old patient with PKU (diagnosed early and treated until the age of 8 years) after
      12 years of normal nutrition and if so, can these changes be counteracted by
      reinstitution of a low phenylalanine diet? METHODS: Psychological (intelligence,
      attention), neurophysiological (evoked potentials) and neuroradiological
      examination (magnetic resonance tomography [MRT] of the brain) were performed
      before and after one year of treatment with a diet low in phenylalanine. RESULTS:
      During the reinstitution of dietary therapy we observed significant improvements
      in attentiveness (percentage increase of 30), whereas intelligence subtests
      remained stable, a reduction in hyperreflexia, shortening of the latencies of the
      evoked potentials and a decrease in periventricular pathological signal
      alterations as evaluated by MRT. CONCLUSIONS: The reintroduction of a diet low in
      phenylalanine improved psychological and neurological symptoms in this PKU
      patient. We recommend a constant low-phenylalanine diet throughout life in
      patients with PKU.

PMID- 10067269
TI  - Primary PTCA versus thrombolysis with tPA in acute myocardial infarction: a
      formal cost-effectiveness analysis.
AB  - AIMS: Information concerning the cost-effectiveness of primary percutaneous
      transluminal coronary angioplasty (PTCA) compared to thrombolytic treatment with
      tissue plasminogen activator (tPA) for the management of acute myocardial
      infarction (AMI) is limited. The existing data are derived from studies using a
      wide range of intervention, re-intervention and a high rate of mortality. The
      present study examined the cost-effectiveness of primary PTCA compared to
      thrombolytic treatment with tPA in the setting of AMI by applying data from
      published prospective randomised studies. METHODS AND RESULTS: We performed a
      formal cost-effectiveness analysis. As estimates for "cost" of therapy we applied
      the reimbursement paid by the public health insurance organisations in Austria.
      Coronary intervention rates and re-intervention rates were extracted from
      published studies. Assuming a moderately reduced in-hospital mortality for
      patients treated with primary PTCA (4.8%) compared to tPA (6.6%) on the basis of
      AMI in a 60-year-old male, the estimated additional cost per life saved was 274.
      ECU (95% confidence interval 231.- to 318.-ECU). However, the cost per life saved
      was sensitive to the given range of intervention and re-intervention rates (range
      2,518.-ECU gain to 9,560.-ECU additional cost). CONCLUSIONS: Assuming a moderate
      in-hospital survival benefit from treatment with primary PTCA in patients with
      AMI, PTCA seems to be cost effective in comparison to treatment with tPA--at
      least from the perspective of cost reimbursement by public health insurance
      organisations.

PMID- 10067270
TI  - Total synthesis of the naturally occurring antibiotic toyocamycin using new and
      improved synthetic procedures.
AB  - Starting with commercially available tetracyanoethylene, we describe a more
      efficient and higher yielding synthesis of toyocamycin with regards to
      convenience, overall yield, and total reaction time than those syntheses
      previously reported.

PMID- 10067271
TI  - A practical synthesis of L-FMAU from L-arabinose.
AB  - A practical synthesis of 2'-deoxy-2'-fluoro-5-methyl-beta-L-arabinofuranosyl
      uracil (14, L-FMAU) was developed from L-arabinose. L-Arabinose was converted to
      L-ribose 5, which was used for the synthesis of bromosugar 12 via 2,3,5-O
      tribenzoyl-1-O-acetyl-beta-L-ribofuranose 8, which was subjected to condensation
      with silylated thymine and the resulting protected L-FMAU 13 was deprotected to
      afford L-FMAU in 14 steps in 8% overall yield.

PMID- 10067272
TI  - Synthesis of fluorescent, photolabile 3'-O-protected nucleoside triphosphates for
      the base addition sequencing scheme.
AB  - The dansylated nucleoside triphosphates 1a and 1b were prepared as a prelude to
      investigating sequencing of DNA via a scheme that does not involve
      electrophoresis.

PMID- 10067273
TI  - The synthesis and antiviral activity of 4-fluoro-1-beta-D-ribofuranosyl-1H
      pyrazole-3-carboxamide.
AB  - A novel fluoropyrazole ribonucleoside has been shown to have significant anti
      influenza activity in vitro. The compound is compared and contrasted with the
      structurally-related compound ribavirin in attempts to identify factors having
      significant bearing on the mode of action of both compounds.

PMID- 10067274
TI  - Synthesis and biological evaluation of a carbocyclic azanoraristeromycin
      siderophore conjugate.
AB  - Synthesis and biological evaluation of a carbocyclic azanoraristeromycin
      siderophore conjugate 22 is reported. Coupling of previously prepared L-alanyl-4'
      azanoraristeromycin 19 with protected tripeptide trihydroxamate 20, followed by
      hydrogenolytic removal of all protecting groups, provided the first carbocylic
      azanoraristeromycin siderophore conjugate (22, 8 with iron). Compounds 19 and 22
      showed inhibitory activity against tumor cells, and conjugate 22, in particular,
      displayed significant activity against those viruses (i.e. reo, parainfluenza,
      vaccinia, cytomegalo) that are known to be inhibited by S-adenosylhomocysteine
      hydrolase inhibitors.

PMID- 10067275
TI  - Synthesis and antiviral activity of novel aza-acyclonucleosides.
AB  - We have prepared a series of novel aza-acyclonucleosides as potential antiviral
      agents. These compounds were prepared from diethanolamine and the desired purine
      or pyrimidine base via a Mitsunobu coupling. No antiviral activity was observed
      against either HSV-1 or HCMV.

PMID- 10067276
TI  - Synthesis of a new class of HIV-1 inhibitors.
AB  - A new family of molecules potentially inhibitors of the HIV-1 Tat-TAR complex was
      prepared. These compounds are constituted by dinucleotide analogs (PNA dimer)
      bound, through a linker, to an arginine residue. In this series, several
      molecules inhibit viral development in cell culture with a micromolar IC50 and
      without cellular toxicity until 200 microM concentration.

PMID- 10067277
TI  - High specific radioactivity labeling of oligonucleotides with 3H-succinimidyl
      propionate.
AB  - An easy and rapid method for tritium labeling of deprotected oligonucleotides is
      proposed. The method consists in performing the reaction of commercial 3H
      succinimidyl propionate with a terminal amino group of the oligonucleotide in an
      organic medium. High specific radioactivity labeling can be achieved with minimal
      radiolysis during long term storage. The synthesis of the nonradioactive congener
      having an identical structure to the labeled compound is also described.

PMID- 10067278
TI  - Synthesis of achiral linker reagents for direct labelling of oligonucleotides on
      solid supports.
AB  - Full experimental procedures for the synthesis of a series of new functional
      linker reagents (14-16) and solid supports (11-13) are reported. The achiral
      linker reagents and supports can be used for high yield incorporation of free
      amino groups, fluorescein or biotin into DNA oligomers.

PMID- 10067279
TI  - [48th general meeting of the Japanese Society of Allergology. Kobe, Japan.
      December 1-3, 1998. Abstracts].

PMID- 10067280
TI  - [Secretory expression of salmon calcitonin in Streptomyces lividans].
AB  - A gene coding for salmon calcitonin precursor (sCT-Gly) was amplified from salmon
      genomic DNA by Polymerase Chain Reaction (PCR) and fused to the expression and
      secretion signals of melC1 amplified by PCR. The fusion gene was cloned into the
      Streptomyces vector pIJ680 and expressed under the control of aminoglycoside
      phosphotransferase gene (aph) promoter. Streptomyces lividans TK54 transformed
      with the expression plasmid (pMS680) secreted biologically active sCT-Gly into
      the culture medium which was confirmed by Enzyme Immunoassay (EIA) and bioassay.
      Production of sCT-Gly by the recombinant strain in YEME medium reached a maximum
      of 100 micrograms/L culture at about 96 h. The recombinant sCT-Gly had almost the
      same HPLC retention time as the standard sCT obtained from Sigma.

PMID- 10067281
TI  - [Studies on DNA damage in human blood lymphocytes using the single cell microgel
      electrophoresis technique].
AB  - In this paper, the single cell microgel electrophoresis (SCG) technique was
      described in detail, and effects of DNA damage of human blood lymphocytes induced
      by gamma-rays radiation, H2O2 and CdCl2 were studied using this technique. It was
      shown that gamma-rays, H2O2 and CdCl2 all caused the increase of DNA migration
      length in the lymphocytes in the dose-dependent manner. The principle of the SCG
      technique, cause of DNA migration in the untreated control cells, and noticeable
      details in the SCG technique were also discussed.

PMID- 10067282
TI  - [Expression and biochemical characterization of human G6PD gene 1376 and 1388
      mutation in G6PD-deficient Escherichia coli].
AB  - Nine types of human G6PD gene mutated at the positions of nt 1376 and nt 1388 by
      site-directed mutagenesis were transformed into the strain of G6PD dificent E.
      coli HB 351(DE3). The mutated gene was expressed successfully and the enzyme
      kinetic studies undertaken according to WHO standardization. The results showed
      that the arginine residues at the positions of 459 and 463 of G6PD gene play an
      important role in maintaining activity of the enzyme. The amino acid structure,
      polarity, and electronic property may be responsible for it. The arginine
      residues at the positions of 459 and 463 are also important for the enzyme-NADP+
      binding, but it was not interfered by the lysine-arginine substitution. By
      inducing a non-sense mutation, it was further demonstrated that the amino acids
      residueds behind the position of 459 were extremely significant for G6PD
      activity.

PMID- 10067283
TI  - [Thermostable alkaline phosphatase from Thermus sp. FD3041: cloning of the gene
      and expression in Escherichia coli].
AB  - A genomic library of Thermus sp. FD3041 which produces thermostable alkaline
      phosphatase (FD-TAP) was constructed with the vector pUC118 and the host E. coli
      TG1. 3-10kb inserted fragments of foreign DNA were identified in 90 percent of
      the 12,000 clones thus obtained. Five positive clones were detected after
      screening the plated library by the method of colony coloration for TAP in situ.
      Preliminary analysis of the enzyme expressed from one recombinant plasmid pTAP362
      showed that the properties of the recombinant enzyme, such as the thermal
      stability and optimal temperature of reaction, were identical to those of the
      native enzyme. The gene of FD-TAP was located on the 2.0kb BamHI-HindIII fragment
      of the pTAP362, determined by its physical map and the change of enzyme activity
      in different partially deleted plasmids. Results of thermostability experiment in
      PCR thermal cycle showed that the FD-TAP would be suitable for labelling of
      primers and detection of PCR amplified products.

PMID- 10067284
TI  - [Role of fundamental research in development of new drugs].

PMID- 10067285
TI  - [Connective tissue dysplasia in idiopathic mitral valve prolapse].

PMID- 10067286
TI  - [Cardioembolic stroke].

PMID- 10067287
TI  - [Viral persistence: immunological and pathogenetic aspects].

PMID- 10067288
TI  - [Hemogram in differential diagnosis of infectious diseases].

PMID- 10067289
TI  - [Beta-adrenergic blockers and calcium antagonists in hypertrophic
      cardiomyopathy].
AB  - Effects of beta-blockers (propranolol, penbutolol) and calcium antagonists
      (nifedipine, verapamil, diltiazem) were studied in 73 patients with hypertrophic
      cardiomyopathy (HC). Clinical data, ECG and echo-CG findings were assessed. It
      was found that beta-adrenoblockers and calcium antagonists improve quality of
      life in one-third of the patients. Penbutolol and nifedipine did so in half of
      the patients. Neither beta-adrenoblockers nor calcium antagonists decrease
      myocardial hypertrophy. Calcium antagonists may result in lowering of myocardial
      contractility while beta-adrenoblockers may increase the ejection fraction.
      Diltiazem produced a positive effect on diastolic function but had many side
      effects. Nifedipine increased lethality compared with verapamil and propranolol.

PMID- 10067290
TI  - [Parameters of variation pulsometry, Q-T interval dispersion and frequency of
      occurrence of late potentials in acute myocardial infarction].
AB  - Registration of standard and high-resolution EGCs, echocardiography in 90
      ischemic heart disease (IHD) patients on myocardial infarction week 2 to 6 has
      demonstrated that deterioration of local myocardial contractility and development
      of left ventricular dilation increase frequency of late ventricular potentials
      and worsen parameters of high-resolution ECG. Left ventricular dysfunction is
      associated with defects in autonomic regulation of cardiac activity. Diminished
      myocardial contractility had no significant effect on dispersion of
      repolarisation.

PMID- 10067291
TI  - [Dynamics of electrophysiological parameters of the heart conduction system in
      patients with alcoholism during long-term therapeutic-vocational rehabilitation].
AB  - Transesophageal pacing in 48 patients with alcoholism stage II made before,
      during and after long-term rehabilitation has shown that initial
      electrophysiological parameters of the heart conductive system were impaired. In
      alcoholics who have abused alcohol for less than 10 years rehabilitation brought
      about positive changes from month 3 to 24 of alcohol withdrawal. Initially
      registered paroxysmal tachyarrhythmia was eliminated. In longer duration of
      alcoholism functional recovery of conductive system of the heart was not
      complete.

PMID- 10067292
TI  - [Acute gastric and duodenal ulcers in burns].
AB  - The authors made a clinical trial of acute gastric and duodenal ulcers arising in
      burnt patients. Treatment results and autopsy material have been analysed for
      1410 and 165 burnt patients, respectively. Of 1410 patients, 8(0.6%) patients
      developed acute gastric and duodenal ulcers. Of 165 dead of burn disease, 23(14%)
      died of gastroduodenal hemorrhage from ulcer lesions. The causes of acute ulcer
      emergence were studied and factors of risk for burnt patients to develop acute
      ulcer and gastroduodenal erosions were determined. This allowed the authors to
      propose measures to prevent onset of acute ulcer in burnt patients.

PMID- 10067293
TI  - [Clinical significance of serum enzymes and proteins in dermatomyositis and
      polymyositis].

PMID- 10067294
TI  - [Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and
      melatonin combined therapy in aged patients with hypertension].
AB  - Effectiveness of Cozaar monotherapy (50 mg at 8 a.m.) was compared to that of
      Cozaar combination with melatonin (3 mg before sleep) in 21 patients with
      hypertension stage II (mean age 62 years). Clinical symptoms and hemodynamic
      parameters were evaluated with ECG and blood pressure monitoring. The findings
      were processed with statistical methods and Kosinor-analysis. Cozaar alone had
      moderate hypotensive and vasodilating effects, affected circadian rhythm of
      systolic and diastolic blood pressure, heart rate. Combination Cozaar + melatonin
      reduced blood pressure more noticeably, diminished cardiac output, energy
      consumption of the myocardium, normalized normal chronostructure of blood
      pressure and heart rate circadian rhythms.

PMID- 10067295
TI  - [Flurbiprofen: pharmacological characteristics and clinical effectiveness].

PMID- 10067296
TI  - [Carcinoid tumors].
AB  - Carcinoid tumors are new growths from neuroendocrine cells. The following
      clinical variants of carcinoid were observed in 11 patients with histologically
      verified carcinoid: 1) asymptomatic variant (an occasional finding at endoscopy)-
      2 cases; 2) carcinoid with symptoms of a mass detected at surgery--2 cases of
      intestinal ileus, 2 cases of appendix carcinoid simulating acute appendicitis; 3)
      carcinoid with hepatic metastases and carcinoid syndrome with unknown primary
      focus--2 cases; 4) carcinoid with metastases to the liver and carcinoid syndrome
      with location of the primary tumor in the lungs (2 cases) and pancreas (1 case).
      It is stated that carcinoid tumors are encountered more frequently than diagnosed
      (0.1-0.5% of all the tumors). Manifestations of carcinoid syndrome allow to
      diagnose carcinoid only at late stage when a large mass of hormone-active tumor
      tissue and metastases to the liver are present.

PMID- 10067297
TI  - [A case of primary actinomycosis of internal female genitalia].

PMID- 10067298
TI  - [Association of untreated lymphogranulomatosis and severe myocarditis].

PMID- 10067299
TI  - [Raising the level of physicians' professional skills by using expert
      examinations on health care quality].

PMID- 10067300
TI  - [Heart failure: limits of classification].

PMID- 10067301
TI  - [Blood group isoantigens in transitional cell carcinoma of the urinary bladder].

PMID- 10067302
TI  - [Usefulness of urethral descent for evaluating the type of female stress urinary
      incontinence].
AB  - BACKGROUND: To select suitable treatment for stress urinary incontinence (SUI),
      both urethral function and urethral mobility must be assessed. Abdominal leak
      point pressure (ALPP) is considered to be useful to evaluate urethral function,
      and radiographic findings are effective to evaluate urethral mobility. However no
      adequate methods to measure urethral mobility with videourodynamics study (VUDS)
      exist. We measured the downward movement of the membranous urethra at the same
      time as ALPP was measured on VUDS, and examined whether or not the urethral
      descent on VUDS is useful to evaluate urethral mobility. METHODS: The subjects
      were 28 women with over grade II SUI (according to McGuire's grading) who
      underwent bead chain cystography and VUDS. As a classical index of urethral
      mobility, we measured the change of posterior urethrovesical angle (PUVA) and
      vesical neck descent during Valsalva maneuver on bead chain cystography. The
      videourodynamic urethral catheter had a radiographic marker that permitted the
      identification of the location of the urethral pressure sensing aperture. The
      catheter was fixed at the position where the urethral pressure aperture reached
      the point of highest pressure. The urethral descent was defined as the downward
      movement of the urethral marker during Valsalva maneuver while measuring ALPP.
      According to the urethral descent the patients were classified as follows: 1)
      hyper-mobile group; urethral descent was over 5 mm. 2) non-mobile group: urethral
      descent was under 5 mm. The severity of SUI was evaluated with 1 hr. pad
      weighting test, ALPP and maximum urethral pressure. RESULTS: The urethral descent
      was significantly related to vesical neck descent and PUVA change. In the non
      mobile group (11 cases), ALPP was significantly lower, and urine loss on the pad
      weighting test was significantly greater than that in the hyper-mobile group (17
      cases). The non-mobile group exhibited more severe incontinence than the hyper
      mobile group. When the patients were classified according to Blaivas's
      classification, all patients in type III and 2 in type I were in the non-mobile
      group. These 2 type I patients had low ALPP (40 cm. water and 70 cm. water) and a
      history of radical hysterectomy. Therefore these patients were diagnosed with ISD
      due to the fixed urethra. CONCLUSIONS: Urethral descent is an useful index of
      urethral mobility. In the non-mobile group, the pathophysiological cause of SUI
      was not urethral hypermobility but ISD, and it was diagnosed as type III SUI
      without urethral mobility. We consider that urethral descent assesses urethral
      mobility more accurately than vesical neck descent, and that urethral descent is
      a valuable parameter on VUDS.

PMID- 10067303
TI  - [Long-term efficacy of the Gittes bladder neck suspension with use of
      ultrasonography for genuine stress urinary incontinence].
AB  - Thirty-eight patients with genuine stress incontinence underwent the Gittes
      procedures of the bladder neck suspension under ultrasonical monitoring. We
      performed the following two procedures. Original Gittes procedure: the puncture
      of the needle made twice through the different holes of the rectus fascia for
      each side and the bilateral helical suture was tied down separately above the
      rectus fascia. Modified Gittes procedure: the needle was passed through the
      rectus fascia once for each side and the both end of the helical suture was drawn
      up to suprapubic area, then the bilateral threads were tied over the rectus
      fascia. Original Gittes procedure was performed for twenty-nine patients and
      modified Gittes procedure for nine patients. Tightness of the suspension was
      decided by monitoring the posterior urethrovesical angle with use of the
      transrectal ultrasonography during the operation. A long term follow up survey
      was made up by means of a questionnaire by the phone or the mail. A total of
      thirty-six patients responded the questionnaire for a 94.7% response rate. The
      mean follow up was 33.1 months. 83.3% of the patients were cured and 5.6% were
      significantly improved. None of the patients claimed dysuria. There was no
      difference between the continent rates of the two procedures. We conclude that
      the Gittes bladder neck suspension with use of ultrasonography is effective for
      correction of female stress urinary incontinence.

PMID- 10067304
TI  - [A clinical study on virilization of external genitalia in congenital adrenal
      hyperplasia].
AB  - PURPOSE: In the newborn female with congenital adrenal hyperplasia (CAH), there
      are variable degrees of clitoral enlargement and virilization of the urethra. In
      order to investigate the factors that cause these variations, the degree of
      musculinization of the external genitalia in 44 patients with CAH was studied
      retrospectively. PATIENTS AND METHODS: This study includes a total of 44 patients
      with CAH aged 2 months to 12 years and 11 months old who had consulted Nagoya
      City University Hospital from 1977 to 1994. The length of clitoris on the first
      consultation was compared with the age and its change was followed. Also, the
      relationship among the length of clitoris on the first consultation, the degree
      of urethral virilization, the clinical forms i.e. salt-losing or simple
      virilization, and the glucocorticoid hormonal condition were investigated with
      each other. In 5 pairs of sisters, the length of clitoris on the first
      consultation was compared within each pairs, and also the degree of urethral
      virilization was compared. RESULTS: The clitoral length on the first consultation
      was significantly correlated with the age (y = 1.8 x + 1.8, r = 0.7, p < 0.0001).
      The mean clitoral length at birth calculated from these data was 18 mm, which is
      as large as that of adult female one, and the clitoral enlargement rate was 1.8
      mm/yr. The correlation was not clear between the clitoral length and the degree
      of urethral virilization, the clinical forms, and the glucocorticoid hormonal
      condition, either. On the other hand, the degree of urethral virilization was
      comparable within clitoral length was not comparable within them. CONCLUSIONS:
      The urethral virilization was suggested to be determined by the internal hormonal
      environment during embryonal stage which was shared by the each pair of sisters.
      On the Other hand, the clitoral length was depend on the patient's age though the
      factor which determined the length was not apparent. These facts indicated that,
      not only the severely musculinizing cases, but also the new born female with
      mildly virilizing urethra should be followed strictly not to undergo the clitoral
      enlargement.

PMID- 10067305
TI  - [Voiding condition in elderly males examined prostate cancer screening in total
      health check and the effect of subjective urinary symptoms on quality of life].
AB  - PURPOSE: We investigated the prevalence of lower urinary tract symptoms and the
      effect of subjective urinary symptoms on quality of life (QOL) in elderly males
      examined prostate cancer screening in total health check from April 1996 to March
      1997. PATIENTS AND METHODS: A total of 922 eligible examinees 50 to 70 years old
      completed a questionnaire with questions worded similarly to those of the
      international prostate symptom score (I-PSS) and AUA Impact index score and so
      on. RESULTS: The prevalence of moderate to severe symptoms was 19.6%, which
      increased with age. I-PSS was well correlated aging but not prostate size. The
      most prevalent symptoms were nocturia (61.1%), frequency (50.0%) and weak stream
      (47.7%). There was good correlation between symptom severity and QOL and AUA
      Impact index scores. While QOL was correlated with obstructive and irritative
      symptom scores, wish for treatment was associated mainly with irritative symptoms
      by multiple regression analyses. However, some examinees (15.5%, 28/181), who had
      moderate to severe symptoms, did not feel a decrease of QOL in daily life.
      CONCLUSIONS: A large percentage of elderly men 50 years old or older experienced
      symptoms. However, subjective urinary symptoms did not always correlate with QOL
      in some individuals. We should independently consider not only symptom severity
      but also QOL and AUA Impact index score in clinical decision making.

PMID- 10067306
TI  - [Indication of repeat prostatic biopsy following previous negative findings].
AB  - BACKGROUND: Many men with clinically suspicious findings would not be diagnosed
      to have prostate cancer. Establishing criteria for indicating repeat biopsy is
      imperative for early detection of prostate cancer. METHODS: Eighty-one patients
      underwent repeat prostatic biopsies under sonographic guidance at Kitasato
      University Hospital between March 1992 and October 1996. Clinicopathological
      parameters such as age, prostate specific antigen (PSA), PSA adjusted for
      transition zone volume (PSAT), PSA density (PSAD), PSA velocity, transition zone
      volume, prostatic volume, rectal findings, ultrasound findings and initial biopsy
      histology were compared with the results of repeat biopsy for searching for
      possible predictors of positive biopsy. RESULTS: Cancer was confirmed in 14
      patients (17.3%), 10 patients by the second biopsy (15.4%, 10/65) and 4 patients
      by the third biopsy (28.6%, 4/14). No cancer was found at the 4th or more
      biopsies. Twelve (85.7%) of these patients had prostatic volume less than 40 cm3.
      Univariate analysis indicated PSAT, PSAD, transition zone volume and prostatic
      volume to be more frequent in men with positive biopsies (p < 0.05). But
      multivariate logistic regression analysis failed to identify any significant
      predictors of positive results in repeat biopsies. CONCLUSIONS: No
      clinicopathological parameters could reliably predict repeat biopsy findings. One
      or 2 additional sets of biopsies is recommended based on clinical judgement
      (symptoms, life expectancy, small glands < or = 40 cm3 etc.) for the purpose of
      early detection of prostate cancer in patients with previously negative biopsy
      but still with suspicious findings in consideration of approximately 20% false
      negative rates by the initial biopsy.

PMID- 10067307
TI  - [A case of renal oncocytoma with cystic formation].
AB  - A 60-year-old man was admitted to our hospital because of a right renal mass
      incidentally detected by ultrasonography during a general health check.
      Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a
      solid mass measuring 6 cm diameter containing a cystic portion in the right
      kidney. Cystic renal cell carcinoma was suspected, and right nephrectomy was
      performed. The gross appearance showed a well circumscribed mahogany brown tumor
      in the lower portion. On cross section of the tumor, a solid mass was seen in the
      cystic portion. Microscopically, oncocytic cells with eosinophilic granular
      cytoplasm were scattered on the cystic wall, and tumor cells formed microcystic
      structures in the solid part. Therefore, the tumor was diagnosed as renal
      oncocytoma with cystic formation. Only twelve cases have previously been reported
      in the literature.

PMID- 10067308
TI  - [Cyclophosphamide-induced bladder cancer in a patient with Wegener
      granuromatosis].
AB  - Cyclophosphamide (CPM) has been considered to be a factor of bladder carcinogen.
      A 60-years old woman had been received a total dose of 370 g of CPM for the
      treatment of Wegener's granulomatosis since August, 1977. She was consulted to
      our department with chief complaint of macrohematuria in August, 1986. Hemorrhage
      cystitis was diagnosed and cystoscopy and urine cytology were performed as follow
      up schedule in every year. In 1996, urine cytology showed class IV and cystoscopy
      revealed multiple nonpapillary tumors. Abdominal computerized tomography
      demonstrated a low density mass on the posterior wall of the bladder. A
      transurethral cold cup biopsy showed G3 transitional cell carcinoma (TCC).
      Radical cystectomy and tubeless cutaneous ureterostomy was performed on December
      6, 1996 and histopathological diagnosis was TCC, G 3, pT3 bNXM0. She died of
      liver failure due to metastatic bladder cancer after seven months
      postoperatively.

PMID- 10067309
TI  - [A patient of successful renal transplantation using donor kidney with congenital
      abnormalities of the inferior vena cava].
AB  - At the time of donor nephrectomy, congenital abnormalities of the inferior vena
      cava was discovered. A 56-year-old woman was worked up preoperatively and no
      abnormalities were found. Abdominal aortography was normal. At the time of
      operation, the inferior vena cava was located to the left and anterior to the
      abdominal aorta. In the renal hilus, the location of the renal artery and vein
      was reversal. We thought the ideas of operation and could successfully performed
      renal transplantation using donor kidney with congenital abnormalities of the
      inferior vena cava.

PMID- 10067310
TI  - [Diagnosis of thyroid nodules by Doppler ultrasonography: a comparison between
      color Doppler and power Doppler ultrasonography].
AB  - The purpose of this study was to assess the usefulness of color and power Doppler
      imaging in thyroid nodules. The following 4 items were compared between malignant
      thyroid nodules (34 cases) and benign nodules (51 cases): 1) vascularity; 2)
      distribution of tumor vessels (none, marginal, peripheral, central); 3) nature of
      tumor vessels (tortuosity, interruption); and 4) FFT analysis. The distribution
      of tumor vessels on color Doppler images, nature of tumor vessels on power
      Doppler images, and the indices of PI, RI, and ATI in FFT analysis were useful in
      making the differential diagnosis between malignant and benign nodules. In terms
      of vascularity, including the distribution of tumor vessels on power Doppler
      images and nature of tumor vessels on color Doppler images, no statistically
      significant differences were found between malignant and benign nodules. Power
      Doppler images depicted tumor vessels in more detail than color Doppler images
      and were considered to extend the application of FFT analysis.

PMID- 10067311
TI  - [Balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric
      varices: therapeutic results and problems].
AB  - PURPOSE: To evaluate the usefulness of balloon-occluded retrograde transvenous
      obliteration (B-RTO) in the treatment of gastric varices. MATERIALS AND METHODS:
      Twenty-one patients with ruptured or high-risk gastric varices underwent B-RTO. A
      5-7F balloon catheter was advanced into the gastrorenal shunt and/or
      gastrophrenic shunt from the femoral vein. Five percent ethanolamine oleate
      iopamidol (EOI) was injected via the balloon catheter or a microcatheter that was
      advanced through the balloon catheter. EOI was withdrawn via the catheter after
      stagnation for 30-60 minutes. Contrast enhanced CT findings, endoscopic findings,
      and liver and renal function tests were evaluated before and after B-RTO.
      RESULTS: Nineteen patients (90%) were successfully treated with B-RTO. In 17 of
      them, CT within two weeks after B-RTO showed complete thrombosis of the gastric
      varices, and the varices had disappeared or markedly regressed on endoscopy after
      1-3 months. In the other two patients, in whom CT showed partial thrombosis of
      the varices, the varices regressed minimally. Liver and renal function tests did
      not show significant changes in 17 of 19 patients (89%). Transient worsening of
      liver function was seen in one patient in whom a small amount of EOI moved into
      the splenic vein during balloon occlusion. Acute renal failure occurred in the
      other patient with the use of 50 ml of EOI. CONCLUSION: B-RTO is an effective
      therapy for gastric varices. However, careful attention should be paid to the
      amount of EOI and hemodynamic change caused by shunt occlusion.

PMID- 10067312
TI  - [CT analysis of mucosal surface dose in intraluminal irradiation for esophageal
      cancer].
AB  - PURPOSE: Balloon applicators are generally used in intraluminal irradiation for
      esophageal cancer. CT exhibits a distortion of the applicator during treatment.
      Because little attention has been paid to dose non-uniformity in the esophageal
      mucosa, we analyzed mucosal surface dose using CT. MATERIALS AND METHODS: Eleven
      patients with esophageal cancer treated with a double-lumen balloon applicator
      (balloon length: 15 cm, diameter: 20 mm) were evaluated. Reference dose was
      prescribed at 5 mm under the mucosal surface. Mucosal surface points were
      determined from CT images, and relative surface dose to reference dose was
      calculated. Hot and cold spots were defined respectively, as dose points
      receiving at least 200% and less than 100% of the reference dose. RESULTS: The
      mean mucosal dose ranged from 138% to 174%. Mucosal dose was distributed widely
      from 100% to 199% in 94% of all patients. Hot and cold spots accounted for 5.3%
      and 0.7% of mucosal dose points, respectively. CONCLUSION: 1) CT analysis
      exhibited the inhomogeneity of esophageal mucosal dose in intraluminal
      irradiation. 2) At present, it is acceptable to prescribe the reference dose at 5
      mm under the esophageal surface. 3) Balloon applicators should be improved to
      achieve dose uniformity in the esophageal mucosa.

PMID- 10067313
TI  - [Clinical results and prognostic factors of radiotherapy for bone metastases from
      breast cancer].
AB  - The purpose of this study was to analyze the results of initial radiotherapy for
      bone metastases (BM) from breast cancer and to investigate the prognostic
      factors. Between 1981 and 1995, 65 women (109 lesions) received initial
      radiotherapy for BM, aiming at a total dose of 50 Gy/25 Fr. Significant relief of
      pain was obtained in 61 (88.4%) of 69 estimable lesions according to the RTOG
      score. The control rates of pain including the prevention of pathological
      fractures or myelopathy were 80.4% at 5 years and 64.3% at 10 years. The median
      survival time of all patients was 11 months, and the survival rates were 56% at 1
      year, 31.6% at 3 years, 17.9% at 5 years and 10.7% at 10 years, with five long
      term survivors. Univariate analysis showed that a normal state of LDH, no other
      metastatic organs, a disease-free interval longer than two years, good
      performance status (0 or 1), BM limited to the axial bones, maintenance chemo
      hormonal therapy and an age of more than 55 years were good prognostic factors.
      Multivariate analysis showed that LDH, age and performance status were
      significant predictors of prognosis. It is important to note the prognostic
      factors at the initial treatment of BM from breast cancer. We consider that
      further prospective studies are needed to determine the optimal treatment
      schedule, including radiotherapy and its combination with chemohormonal therapy,
      for BM.

PMID- 10067314
TI  - [3D-CT cystography of submucosal elevated lesion of the bladder: report of two
      cases].
AB  - We report 2 cases of rare inflammatory disease of the bladder arising from the
      bladder submucosa: eosinophilic cystitis in a 33-year-old woman and inflammatory
      pseudotumor of the bladder in a 41-year-old man. 3D-CT cystography demonstrated
      submucosal tumorous lesions clearly and enabled the evaluation of mucosae of
      lesions especially showed the bridging fold-like appearance of the submucosal
      tumorous lesion in eosinophilic cystitis.

PMID- 10067315
TI  - [Object analysis of cervical lymph nodes using MRI turbo-STIR sequence in cases
      of head and neck tumors].
AB  - Diagnosis of cervical lymph nodes from head and neck tumors was studied using MRI
      turbo-STIR (short TI inversion recovery) sequence and conventional MRI sequence
      in 15 patients. After the MRI examination, 10 of the 15 patients underwent
      radical neck dissections. The detection of cervical lymph nodes with the
      conventional MRI was not clear. However, MRI turbo-STIR depicted clear cervical
      lymph node margins by selectively suppressing fat signals. Thus, the accuracy of
      diagnosis of cervical lymph nodes by the turbo-STIR was higher than by
      conventional MRI. On the other hand, differential diagnosis between metastatic
      and non-metastatic lymph nodes remains difficult only by turbo-STIR. These
      findings suggest that MRI turbo-STIR sequence is more useful in the detection of
      cervical lymph nodes than the conventional MRI methods.

PMID- 10067316
TI  - [An experimental study of the protective effect of lazaroid (U-74389G) on
      cisplatin-induced toxicity].
AB  - Lazaroids, a novel series of 21-aminosteroids without glucocorticoid action, have
      the properties of free radical scavenging and potent inhibition of lipid
      peroxidation. U-74389G is one of the Lazaroid compounds. These compounds have
      shown excellent effect on central nervous system trauma and ischemia in
      experimental animals. The present study was designed to investigate whether
      Lazaroid (U-74389G) has a protective effect on Cisplatin (CDDP)-induced toxicity.
      Fisher 344 rats were used in this study. The animals were divided into three
      groups: I) CDDP 0.9 mg/kg i.v. alone; II) CDDP 0.9 mg/kg i.v. 1 hr after the p.o.
      administration of U-74389G 10 mg/kg; III) physiological saline 2.5 ml/kg i.v.
      instead of CDDP, for 7-10 days. First, the protective effect of Lazaroid (U
      74389G) on CDDP-induced ototoxicity was studied. Cochlear damage was evaluated by
      means of the compound action potential (CAP) and histological examination using
      scanning electron microscopy. The degree of elevation of CAP thresholds and the
      rate of missing outer hair cells were significantly reduced in Group II as
      compared to Group I. These results clearly demonstrate that Lazaroid (U-74389G)
      has a protective effect on CDDP-induced ototoxicity. Second, the protective
      effect of Lazaroid (U-74389G) on CDDP-induced nephrotoxicity was studied.
      Nephrotoxicity was evaluated by means of serum BUN level and histopathological
      examination. There was no significant difference in serum BUN level and little
      difference of renal histopathological findings between Group I and Group II.
      Lazaroid (U-74389G) was not found to ameliorate CDDP-induced nephrotoxicity.
      Third, the influence of Lazaroid (U-74389G) on the antitumor effect of CDDP was
      investigated in rats inoculated subcutaneously with SCC-158 squamous-cell
      carcinoma cells. There was no significant difference of Tumor Growth Rate (TGR)
      between Group I and Group II. The result suggests that the combined
      administration does not alter the antitumor activity of CDDP. In conclusion, the
      combined administration of CDDP with Lazaroid (U-74389G) ameliorates CDDP-induced
      ototoxicity without decreasing the antitumor activity of CDDP.

PMID- 10067317
TI  - [Calcifying epithelioma observed in the anterior auricular region].
AB  - Three cases of calcifying epithelioma observed in the anterior auricular region
      are reported. The ages were 9 to 15 years, and all were females. The size of the
      tumors ranged from 20 x 20 mm to 22 x 34 mm. One case showed elevated (4.1 ng/ml)
      SCC antigen preoperatively, however, the value was reduced within the normal
      range (1.3 ng/ml) after removal of the tumor. One case showed a fistula with
      brownish and serous discharge on the epithelial surface of the tumor. In the same
      case, mitotic change of basophilic cells in the tumor was observed, however,
      distinctly malignant changes such as cell invasion into the surrounding tissue
      were not observed. Although the head and neck region are the most common areas
      where calcifying epithelioma occur otolaryngologists do not have sufficient
      understanding of this disease. Therefore, epidemiology, clinical findings,
      clinical examination, pathology, therapy and prognosis of calcifying epithelioma
      were discussed.

PMID- 10067318
TI  - [Age-dependent changes in dynamic body balance as evaluated by the Body Tracking
      Test (BTT)].
AB  - Stability of Posture and gait decays with aging. In this study, we constructed
      the Body Tracking Test (BTT), to evaluate dynamic body balance function as
      opposed to static balance. Healthy volunteers of various ages (total, 272
      persons) were subjects of the study. The principle of the BTT was for the subject
      to attempt to track an optical moving target displayed on a computer screen by
      shifting his or her body's center of gravity that was also displayed. The target
      moved for a span of 15 cm horizontally on the 14-inch screen, and also, in
      lateral and antero-posterior (horizontal and vertical) on CRT directions at a
      constant velocity of 0.125 Hz. Sixty-seconds recordings are obtained. In BTT, the
      gain for target against tracking was fixed at 2.0 (target:tracking = 1:2). The
      target was 100 cm anterior to the platform where the subject stood erect with the
      feet close together. The criteria for evaluation of the tracking function were
      determined by our preliminary study, titled "Index of BTT movement", and was
      useful during our present study. These criteria were determined ranking to E from
      A. The A rank indicated best tracking. Determination of rankings were performed
      by good or not tracking line against target trace line on recorded papers. Age
      dependent changes in scores were obtained and analyzed. Results suggested that
      the tracking ability started to deteriorate after age 40, and these differences
      were observed in lateral and antero-posterior (horizontal and vertical on CRT)
      directions for all age groups. Tried for a with 30 years old changes, increase of
      a rate that A ranking occupies with a lateral direction law fast stimulation BTT
      from 20-year-old changes though, didn't try for a significant difference with a
      antero-posterior direction law fast stimulation BTT. Try start were 50-year-old
      changes with an antero-posterior BTT, 40-year-old changes with a lateral BTT E
      ranking. C, D, rate that E ranking occupies increases consequently to become 80
      year-old changes and advanced age from 60 years on. For the tendency, a small
      tendency tried for the rate for antero-posterior stimulation BTT compared with a
      lateral stimulation BTT. Whether thought about for this, an of direction is
      prompt nearly against an outside stimulation since it keeps a balance with
      standing and being mended.

PMID- 10067319
TI  - [Epidemiology of Japanese cedar pollinosis: result of the survey in Mibu-machi].
AB  - The prevalence rate of Japanese cedar pollinosis has increased since 1979. We
      conducted a survey of the residents of Mibu-mach, Tochigi, in 1988 and 1996 using
      a questionnaire to determine the prevalence rate of cedar pollinosis. Results
      showed its rate was 15.6% in 1988, and 25.6% in 1996. Age distribution analysis
      of patients with Japanese cedar pollinosis showed the highest prevalence in
      patients between the ages of 10 to 49 years in 1988, and between the ages of 10
      to 59 years old in 1996. Within these age groups, the majority of the patients
      were females, but males were more prevalent than females in the age group under
      19 years old. The prevalence rate of patients by age group revealed the same
      pattern as the age distribution of the patients. Age distribution of cedar
      pollinosis showed a peak in patients in their thirties both in 1988 and 1996. In
      conclusion, the numbers of patients with Japanese cedar pollinosis has been
      increasing remarkably in Mibu-mach. As climate or environmental conditions are
      varied in different geographical regions in Japan, further epidemiological
      studies in various regions of the country are required to clarify the actual
      prevalence rate of cedar pollinosis.

PMID- 10067320
TI  - [Three-dimensional analysis of eye movements induced by off-vertical axis
      rotation].
AB  - Off-vertical axis rotation (OVAR) is a method to stimulate the otolith organ. In
      order to elucidate the function of the otolith organ, we analyzed three
      dimensional eye movements by video-oculographic technique during OVAR in 30
      normal subjects. The eye movements induced by OVAR stimulation have two
      components: a constant horizontal deviation in the direction opposite to the
      rotation known as the bias component, and sinusoidal amplitude changes of eye
      movements known as the modulation component. Modulation components were detected
      in the horizontal, vertical, and torsional eye movements, but the bias components
      were only detected in the horizontal eye movements. The modulation components may
      compensate for changes in head orientation with respect to gravity. Since the
      bias component is caused by the velocity storage mechanism, the lack of bias
      components in vertical and torsional eye movements may suggest its specific
      relation to only horizontal eye movements. Our results also demonstrated that
      torsional and horizontal eye movements may originate from the utricle, whereas
      vertical eye movement may originate from the saccule. However, a lag phase
      between torsional and horizontal eye movements suggests that the most effective
      direction for stimulation of these two eye movements may be different.

PMID- 10067321
TI  - [The influence of dorsal neck proprioceptive inputs on vestibular compensation-
      by three-dimensional analysis of neck-induced nystagmus].
AB  - The influence of dorsal neck proprioceptive inputs on vestibular compensation was
      investigated in 21 patients with unilateral vestibular dysfunction. Subjects
      neither had history of spontaneous nystagmus nor of disequilibrium, indicating
      that they were in a good compensated stage. However, marked nystagmus was induced
      by applying vibratory stimulation to the dorsal neck of the patients, using a
      vibrator with a frequency of 110 Hz. The nystagmus was three-dimensional as
      analyzed by applying computerized eye movement analysis system. Twelve of 21
      patients (57%) demonstrated three components of eye movement. All subjects showed
      a horizontal component directed towards the contralateral side of the vestibular
      lesion. Vertical and torsional components of the nystagmus were exhibited by 18
      and 14 subjects, respectively. The average percentages of slow phase velocity of
      the horizontal, vertical and torsional components were 57%, 23% and 20%,
      respectively. No tendency towards any of the three components was observed.
      Furthermore, in order to investigate the relation between dorsal neck
      proprioceptive inputs and vestibular outputs, especially semicircular canal
      outputs, the author compared the direction of the nystagmus with the orientation
      of the semicircular canals. Normalized average velocity vectors of the nystagmus
      were calculated. In most subjects, the velocity vectors of the nystagmus were
      related to the horizontal semicircular canal. These results suggest that by
      controlling the neck proprioceptive inputs, neck vibration can cause
      discompensation in vestibularly well-compensated subjects with unilateral
      dysfunction secondary to vestibular lesion, and that neck proprioceptive inputs
      have a great influence on the horizontal vestibulo-ocular reflex pathways.
      However, in a few subjects the average vectors of the nystagmus were related to
      the vertical semicircular canals. This suggests that the proprioceptive inputs
      may also be related to the vertical vestibulo-ocular reflex pathways.

PMID- 10067322
TI  - [Prediction about daily scattering count of Japanese cedar pollen].
AB  - We investigated the relationship between the daily count of pollen scattered, the
      count of days during the scattering period and the highest temperature during the
      sugi (Japanese cedar) pollen scattering season from 1983 to 1997, and whether
      prediction of the count of pollen scattered for the following day is possible.
      Our studies clearly demonstrated that the count of sugi pollen scattered is small
      in the early period of the scattering season with some daily variations in
      amount; this cycle is repeated for several days in the middle period of the
      season then decreases again in the late period. These findings showed that both
      the cumulative value of the count of pollen scattered daily and the total count
      of pollen scattered formed an S-shaped curve when compared with the count of days
      after the start of the scattering season and the cumulative highest temperature
      for the season. Predicting the daily count of pollen scattered after the start of
      the scattering season against the cumulative highest temperature is possible by
      drawing a regression curve from the S-shaped curve. Also, a regression curve was
      useful in predicting the total count of pollen scattered during the season from
      the cumulative count of pollen scattered 10 to 20 days after the start of the
      scattering season. Using these data, we were able to improve the accuracy for
      predicting the scattering of sugi pollen.

PMID- 10067323
TI  - [Cytokine production of peripheral mononuclear cells in HD-mite-allergic rhinitis
      patients].
AB  - To elucidate the role of cytokines in the pathogenesis of allergic rhinitis, the
      proliferative response and cytokine production of peripheral mononuclear cells
      (PMNC) following stimulation with mite-antigen were evaluated in HD-mite-allergic
      rhinitis patients (mite-allergy group), non-HD-mite pollinosis patients (non-mite
      allergy group) and normal subjects (normal group). The proliferative response of
      PMNC to PHA stimulation was not different among the groups, whereas that to mite
      antigen stimulation was significantly higher in the mite-allergy group than in
      the normal group. Production of both IL-4 and IL-5 from PMNC after stimulation
      with mite-antigen was significantly higher in the mite-allergy group than in the
      normal group. Production of IFN-gamma from PMNC after antigen stimulation was
      significantly increased in both the mite-allergy and normal groups. The ratio of
      IFN-gamma to IL-4 synthesis was significantly higher in the normal group than in
      the mite-allergy group. This study revealed cytokine synthesis from PMNC after
      the antigen-stimulation was predominantly Th2-cytokines in patients with HD-mite
      allergic rhinitis.

PMID- 10067324
TI  - [Influence of age on vestibulo-ocular reflex (VOR)].
AB  - In this article we discuss the influence of age on the vestibulo-ocular reflex in
      a comparison of data from different age groups. In order to examine the influence
      of age, the pendular rotation test was performed in 25 otoneurologically healthy
      subjects and 12 patients with unilateral peripheral vestibular disorders, from 25
      to 72 years of age. The subjects were divided into three groups: 20-39, 40-64 and
      older than 65 years. The stimulus modes were an amplitude and a frequency of 30
      degrees at 0.25 Hz and of 60 degrees at 0.1 Hz, respectively. The gain, phase lag
      and visual suppression in VOR of the pendular rotation test were measured, and
      the age-dependent changes in these scores were evaluated. The following results
      were obtained: 1. The gain in VOR with eyes open in a dark booth was
      significantly decreased in the older than 65 years group. 2. The phase lag was
      significantly increased in the older than 65 years group. 3. There were no
      significant differences of VOR-visual suppression between any of the age groups.
      The gain in normal subjects was significantly larger than that of the affected
      side in patients with unilateral peripheral vestibular disorders. The phase lag
      in patients with unilateral peripheral vestibular disorders was significantly
      larger than in normal subjects. Similar to normal subjects, this stimulation
      caused no significant differences in the VOR-VS between the affected side and the
      normal side in patients with unilateral peripheral vestibular disorders.

PMID- 10067325
TI  - [The 100th anniversary of the Japanese Journal of Gastroenterology 1898-1998].

PMID- 10067326
TI  - [Exudative retinal detachment surgery. A prognostic++ parameter of malignant
      melanoma in brachytherapy?].
AB  - BACKGROUND: The purpose of this study was to compare the regression of the tumor
      distant exudative detachment that accompanies malignant melanoma with regression
      of the tumor as a result of ruthenium-106 irradiation. METHODS: From 1994 until
      the beginning of 1996 we treated 28 patients with choroidal malignant melanoma
      with radioactive plaque therapy. Follow-up examinations were completed 3 and 6
      weeks, 3, 6 and 12 months after therapy and finally at 1 year or half-year
      intervals. Twenty-three patients met the study requirements. RESULTS: Initially,
      after irradiation there was an increase in the retinal detachment. In 15 patients
      (65%) we found rapid regression of the detachment, accompanied by distinct tumor
      regression (61%). One of these patients revealed only minor tumor regression in
      spite of regression of the exudative detachment. Three months after radiation, 8
      patients showed no rapid regression of the exudative detachment. Two of these
      patients had to undergo a second irradiation and 2 were enucleated because of
      absent tumor regression. One patient died. Three patients showed an increase in
      the detachment, accompanied by tumor regression. CONCLUSIONS: Rapid regression of
      the exudative detachment (> or = 50% of the preoperative detachment)
      approximately 3 months after irradiation seems to be of good prognostic value for
      tumor regression.

PMID- 10067327
TI  - [Serous central chorioretinopathy. Acute autofluorescence of the pigment
      epithelium of the eye].
AB  - PURPOSE: The lack of histopathological material has placed limitations on our
      knowledge on lipofuscin in central serous chorioretinopathy (CSCR). This study
      was designed to document the pathological changes of the retinal pigment
      epithelium (RPE) in CSCR using in vivo recording of fundus autofluorescence.
      METHODS: Fundus autofluorescence was documented in 62 eyes of 44 subjects with
      CSCR using a laser scanning ophthalmoscope (Zeiss, Oberkochen; excitation
      wavelength: 488 nm, barrier filter at 521 nm). Images were compared to the
      respective fundus appearance and fluorescein angiograms. RESULTS: Neurososensory
      retinal detachments showed diffuse increased autofluorescence corresponding to
      the detached area. Long-standing lesions showed very irregular autofluorescence
      with regions greater and less than the background levels of autofluorescence.
      CONCLUSION: Focal accumulation of autofluorescent material occurs at the level of
      the RPE in patients with CSCR, relating to variation in metabolic activity of the
      RPE. This technique may be useful in selecting patients for laser
      photocoagulation.

PMID- 10067328
TI  - [Cytomegalovirus (CMV) retinitis in AIDS. Gancilovir implantation in comparison
      with systemic therapy].
AB  - INTRODUCTION: Untreated CMV retinitis with AIDS leads to blindness; therefore, a
      life-long virostatic treatment is required. It can either be administered
      systemically or locally, as there are different advantages and disadvantages.
      When treating patients we aim at therapy that preserves vision without
      diminishing quality of life. It should induce as few drug-induced side effects as
      possible and not shorten the patient's life expectation. METHODS AND RESULTS: A
      total of 111 patients (150 eyes) with systemic maintenance treatment were
      compared retrospectively with 33 patients (62 eyes) that received a ganciclovir
      implant only as maintainance therapy and no additional systemic treatment.
      Patients with an implant showed a prolonged interval of nonprogression of
      retinitis than patients receiving systemic treatment. Patients with unilateral
      retinitis are at higher risk of developing bilateral disease in the implant group
      than in the systemically treated group. Manifestation of extraocular disease was
      equal in both groups. Local treatment with the implant does not shorten patient
      survival time. CONCLUSION: Local treatment with the ganciclovir implant means
      quality of life for patients and also safe protection of the affected eye.
      Extraocular disease and survival time are not influenced adversely by local
      treatment. However, primarily unilateral involved patients show higher risk for
      bilateral disease in the implant group than in the systemically treated group.

PMID- 10067329
TI  - [Surgical suction in cataract extraction. Postoperative follow-up in 219 cases
      over 16 years of age].
AB  - Nd-YAG posterior capsulotomy in treatment of secondary cataract has the main
      disadvantage of increasing the risk for pseudophakic retinal detachment by
      destroying the posterior lens capsule. This is of great interest in high myopic
      eyes with an increased risk for pseudophakic retinal detachment. In 219 cases of
      secondary cataract in our clinic a surgical posterior capsule polishing has been
      performed and this group was followed up over 6 years looking for intra- and
      postoperative complications. PATIENTS: The examined group included 209 myopic
      eyes with a bulbus length > 25 mm and 10 eyes with traumatic cataract; 24 eyes of
      this group had been primarily operated without a lens. The secondary cataract
      surgery was performed between 1990 and 1995, and the average follow-up period was
      42 months. The intra- and postoperative complications were revealed
      retrospectively by examination of the patients in our clinic or by interviewing
      the patients' private doctors. RESULTS: The patients achieved a mean improvement
      in vision of 4 lines. In 9 cases intraoperative capsule rupture occurred (4%). In
      35 of the operated eyes one or more relapses occurred during the follow-up period
      that made another polishing necessary (16%), and in 5 cases YAG capsulotomy was
      eventually performed (2%). Pseudophakic retinal detachment occurred in none of
      the cases. CONCLUSION: Surgical posterior capsule polishing is a low-risk
      procedure for treatment of regenerative secondary cataract. It is indicated
      especially in myopic eyes in order to reduce the risk of pseudophakic retinal
      detachment by conserving the posterior lens capsule.

PMID- 10067330
TI  - [Biocompatibility of flexible intraocular lenses in vivo].
AB  - PURPOSE: One aspect of biocompatibility of IOLs can be tested using specular
      microscopy of the anterior and posterior surface of the lens in vivo. METHODS: We
      examined 45 patients after implantation of a "Memory lens" and 31 patients after
      the implantation of an "Acrysof" lens 3-6 months after surgery. RESULTS: Typical
      deposits (Lens epithelial cells, spindle-shaped macrophages, giant cells,
      pigment, Wolter membrane) were rarely seen on both types of lenses. There were
      fewer lens epithelial cells on the posterior capsule and less secondary cataract
      after implantation of the "Acrysof" lens. CONCLUSIONS: We did not find any
      indication of reduced biocompatibility in any of the lenses examined. The reduced
      rate of secondary cataract after implantation of the "memory lens" may be
      explained by the fact that this lens type sticks to the posterior capsule better.

PMID- 10067331
TI  - [Retinal hemodynamics in patients with normal pressure glaucoma. Quantification
      with digital laser scanning fluorescein angiography].
AB  - Chronic ischemia of the retina and the optic nerve head seems of importance
      especially in patients with normal-tension glaucoma (NTG). The purpose of this
      study was to examine the retinal hemodynamics in patients with NTG. PATIENTS:
      Twenty-five patients with NTG were examined (3 weeks washout period) in this
      study (age 58 +/- 16 years). The arteriovenous passage (AVP) time and arterial
      and venous diameters from scanning laser fluorescein angiograms were evaluated by
      means of digital image analysis. RESULTS: The AVP time in patients with NTG (2.78
      +/- 1.1 s) was significantly prolonged (P < 0.0001) compared with healthy
      subjects (1.58 +/- 0.4 s). No significant correlation was found between arterial
      and venous diameters, intraocular pressure, blood pressure or calculated
      perfusion pressure and retinal arteriovenous passage time. CONCLUSION: Patients
      with NTG showed prolonged retinal passage, which could cause chronic hypoxia.
      This prolongation of circulation is not correlated with any of the clinical
      parameters. Thus, a circulatory defect might be a primary factor in the
      pathogenesis of NTG.

PMID- 10067332
TI  - [Motif expressing soft print lenses. Effect on visual function].
AB  - BACKGROUND: Contact lenses which change the structure and color of the iris are
      used not only for many therapeutic situations but also for cosmetic reasons. The
      purpose of this study was to investigate whether such lenses cause impairment of
      visual functions. MATERIAL AND METHODS: In healthy volunteers with an uncorrected
      visual acuity of 20/20 a clear soft-fitting lens and a special effect soft
      contact lens (Crazy lens, Bach Optic, Cologne) were tested in changing sequence.
      The following parameters were studied: visual acuity, contrast sensitivity (MCT
      8000, VisTech Cons., Dayton, Ohio), Goldmann visual field, mesopic vision
      (Nyktometer, Rodenstock, Munich), and subjective wear comfort on a scale from 1
      (excellent) to 10 (poor). Statistical analysis was performed using the Wilcoxon
      test and the Mann-Whitney U-test. RESULTS: Nine volunteers with a mean age of
      29.9 +/- 5.1 years were analyzed. Visual acuity was reduced to 0.9 +/- 0.23 in
      the Crazy lens group compared to 1.2 +/- 0.13 in the clear lens group. Mesopic
      vision without glare was reduced from 1:2.5 to 1:7.4. Goldmann visual field
      displayed a significant constriction of following isopters: III/4, I/4, and I/3.
      Contrast sensitivity was significantly reduced in a photopic condition with and
      without glare and in a scotopic condition without glare; there was, however, an
      increase in contrast sensitivity in a scotopic condition with glare. Furthermore
      a decrease in wear comfort from 2.8 +/- 1.4 with the clear fitting lens to 5.7 +/
      2.1 with the print-lens was found. CONCLUSION: The tested special-effect contact
      lenses are associated with a reduction of many visual functions, including visual
      acuity and contrast sensitivity. This may interfere in some wearers with the
      ability to drive a car.

PMID- 10067333
TI  - [Long-term results of secondary orbital implants].
AB  - BACKGROUND: Secondary orbital implants are used for the correction of the post
      enucleation socket syndrome (PESS). This study evaluates retrospectively the post
      operative course, complications, additional surgery, long-term cosmetic and
      functional results, and patient's satisfaction after secondary orbital implants.
      PATIENTS: Nineteen out of 24 patients who underwent secondary baseball implant
      insertion between 1986 and 1989 for the correction of PESS were re-examined.
      RESULTS: Five patients had complications, 11 patients (58%) further surgery.
      After a mean follow-up of 8.6 years, 17 patients (89%) showed findings better
      than preoperatively. Two patients were unchanged. The static overall impression,
      assessing particularly volume deficit and symmetry, using a scale of 1 to 5, was
      improved from 4.5 preoperatively to 2.5. CONCLUSIONS: Secondary orbital implants
      improve symptoms of PESS and patient's satisfaction in a high proportion of cases
      also in the long term. Complications are not rare, and frequently more than one
      operation is necessary. There is no significant risk of long-term side effects
      and no reduction of the positive effect with time.

PMID- 10067334
TI  - [High endothelial venules. Kinetics of the expression in IRBP-induced
      experimental autoimmune uveitis].
AB  - Experimental autoimmune uveitis (EAU) is a T-cell-mediated disease expressing
      high endothelial venules (HEVs) in the retina. HEVs could be responsible for the
      absorption of activated T-cells. The purpose of this study was to investigate the
      kinetics of HEV expression in the murine IRBP (interphotoreceptor retinoid
      binding protein) induced EAU. METHODS: B10. A mice were immunized subcutaneously
      with IRBP. The eyes were analysed on days 10, 18, 24 and 28 (n = 5 for each time
      point). While HEVs were identified with the mAb MECA 325, the control mAb MECA 20
      stained all endothelial cells. RESULTS: HEVs were detectable in the intact retina
      from day 10. Presence of HEVs peaked on day 18 and decreased by day 28, when
      maximal inflammation and retinal destruction was detectable. CONCLUSION: HEV
      expression could play a central role in the onset of EAU, allowing homing and
      migration of inflammatory cells into the eye.

PMID- 10067335
TI  - [Therapy-refractory iridocyclitis in pseudophakia. Chronic low-grade
      endophthalmitis after cataract operation, induced by propionibacteria].

PMID- 10067336
TI  - [Combined cataract and glaucoma surgery].

PMID- 10067337
TI  - [Pulmonary tuberculosis: data of general somatic hospital].
AB  - About 20% of phthisiatric patients are identified among pulmonological patients
      treated in general hospitals. These include not only the subjects having
      indications in the history, signs of prior tuberculosis and being at risk for the
      disease, but those with the first detected specific changes in the lung and
      unregistered in the dispensary, as well as its contingents (including patients
      with active and basilar pulmonary tuberculosis). In this connection, this
      emphasizes that the physicians of general somatic hospitals should be more
      phthisiologically alert by taking into account the poor tuberculosis situation in
      the country.

PMID- 10067338
TI  - [Analysis of tuberculosis quality diagnosis by autopsy data].
AB  - The records of autopsies and history cases of deceased patients served as a
      material for analyzing the quality of clinical diagnosis of tuberculosis in 1987
      1997. A hundred and eighty and six patients (39.1%) were autopsied. Of them 139
      (74.7%) and 47 (25.3%) died from tuberculosis and other diseases, respectively.
      Tuberculosis and its complications were recognized in 113 (81.3%) patients during
      their life. Fibrocavernous tuberculosis was a prevalent clinical form in 104
      (55.9%) of the deceased. Progressive tuberculosis, more commonly as complications
      of cavernous tuberculosis (in 49 (35.2%) patients) and those of hematogenic
      generalization (in 23 (16.5%)) were a direct cause of death in most tuberculosis
      patients (n = 72 (51.8%)).

PMID- 10067339
TI  - [Problems and specific features of antituberculous work among pediatric
      population].
AB  - The paper defines the problems and priorities in putting antituberculous measures
      into effect among children. The formation of risk groups, the use of the
      compulsory diagnostic minimum during their examination for tuberculosis, the
      increase of the scope and quality of immunoprophylaxis, the phthisiologist's
      contacts with general medical network are the main thing in work on early
      detection and prevention of tuberculosis. The sanatorium stage assumes a great
      significance under the present conditions due to changes in the periods and
      treatment regimen of patients with tuberculosis.

PMID- 10067340
TI  - [Some specific features of temporary and persistent disability in patients with
      pulmonary tuberculosis].
AB  - Disability was analyzed in 270 patients with pulmonary tuberculosis detected in
      1995-1997. Today the level of disability and its associated expenses on payment
      of allowances due to the working incapacity of patients with pulmonary
      tuberculosis are more and more determined by different poor social factors, such
      as the specific features of the labour market, unemployment, lower living
      conditions of most patients with this disease.

PMID- 10067341
TI  - [Clinical and epidemiological characteristics of patients with eye tuberculosis].
AB  - The study has analyzed 514 new cases of eye tuberculosis registered in the
      dispensaries of 23 regions. Eye tuberculosis more frequently affects young and
      middle-aged women, urban citizens, persons who have adequate living and domestic
      conditions, moderate income, who are clerks or skilled workers, who have no bad
      habits, who suffer one or two concurrent diseases, who have no opportunity of
      receiving adequate treatment in a hospital or sanatorium due to familial or
      professional circumstances and more commonly those whose posterior eyeball is
      involved (chorioretinitis). Of great concern is eye tuberculosis detected in
      87.4% of referrals, which determines the high proportion of advanced and far
      advanced cases.

PMID- 10067342
TI  - [Clinical, immunological and psychiatric characteristics of tuberculosis
      infection initial period in adolescents].
AB  - Variability of tuberculin reactions in adolescents may be represented by changes
      of a negative tuberculin test to a positive or false one, then to a positive
      test. Adolescents primarily infected with tuberculosis have predisposing factors:
      inadequate immunoprophylaxis contact with tuberculosis patients, discord in
      physical development, hyperergic sensitivity to tuberculin, which can determine a
      further course of tuberculosis infection. The variability of tuberculin reactions
      in adolescents is characterized by changed immunological responsiveness as higher
      immunospecific parameters and lower nonspecific responsiveness parameters, as
      well as decreased attention; there is a trend for frequent development of primary
      infection in persons having character accentuation. The aforesaid allows the
      variability of tuberculin reactions to be regarded as "minor disease".

PMID- 10067343
TI  - [Carbohydrate metabolism in children with pulmonary tuberculosis].
AB  - Examining carbohydrate metabolism in 59 children with pulmonary tuberculosis
      ascertained that to get tuberculosis naturally resulted in lower tissue
      sensitivity to insulin and in hyperinsulinemia. Effective treatment of children
      improves carbohydrate metabolism. However, there is no normalization of
      carbohydrate metabolism even in clinical cure.

PMID- 10067344
TI  - [Detection of antituberculosis antibodies and antigens by enzyme immunoassay in
      young and preschool children suffering from tuberculosis].
AB  - Antituberculosis antibodies and mycobacterial antigens were detected in 74 young
      and preschool children suffering from tuberculosis by using enzyme immunoassay
      (EIA). They were found in 75.7% and 68.9% of children, respectively. The highest
      levels of antibodies were significantly greater in patients with active
      disseminated processes than in those with active restrictive processes. There
      were no great differences in the levels of antigens between the patients having
      different activities of a tuberculosis process. Follow-up indicated that there
      was a reduction in the levels of antibodies and antigens at 6-month treatment.
      The use of enzyme EIA in children ill with tuberculosis may serve an additional
      criterion for diagnosis of tuberculosis, evaluation of its activity and course.

PMID- 10067345
TI  - [Immunotherapy of pulmonary tuberculosis].
AB  - The efficiency of treating patients with destructive tuberculosis by using
      different immune correctors was comparatively analyzed. Five hundred and fifty
      three patients were treated with thymalin, thymogen, human leukocytic interferon,
      and a combination of thymogen and interferon. The benefit from immunocorrector
      treatment was obtained early in the complex therapy and the best result was
      achieved by the use of thymogen plus interferon. However, the action of the two
      immunocorrectors increased when fibrous deformity of the lung was healed,
      followed by the development of pronounced residual changes.

PMID- 10067346
TI  - [Late results of multistage polysegmental lung resection for tuberculosis at many
      sites].
AB  - The late outcomes of surgical treatment of 124 patients operated on for pulmonary
      tuberculosis at many sites were analyzed. Surgery was made in the anatomic
      variant of typical polysegmental resections involving 3 to 7 bronchopulmonary
      segments in combination with a number of additional elements. The stable cure
      rates were 77.7, 71.2, and 64.3% at 3-, 5- and 10-year follow-ups, respectively.
      The maximum relapse rates at 2- and 3-year follow-up were 9.5 and 9.2%,
      respectively with variations in some subgroups according to the type of
      resection, the clinical forms of tuberculosis, the bacteriological activity of
      the process by surgery and the drug resistance of Mycobacteria. The cumulative
      adjusted survival rates in the same periods were 92.1, 85.1, and 70%,
      respectively, with the maximum mortality rate (6.8%) at 3-year follow-up, they
      being ranged under the influence of the above risk factors. No systematic
      controlled preventive chemotherapy regimens are a cause of relapses and death in
      the late periods of follow-ups.

PMID- 10067347
TI  - [Clinical and morphological characterizations of first detected cases of caseous
      pneumonia and its outcomes under conditions of current antibacterial therapy].
AB  - The paper provides a clinical and X-ray picture of first detected caseous
      pneumonia. It shows the potentialities of currently available antibiotic therapy
      used in patients with this diagnosis. At the same time closure of decay cavities
      and eradication of bacteria can be achieved only in 29% of cases. The major
      outcome of caseous pneumonia is fibrocavernous tuberculosis. Thus, surgical
      methods must play an important role in curing such patients. A detailed
      morphological characterization of surgical materials has demonstrated that active
      chemotherapy may result in 3 types of caseous pneumonia outcomes: acute
      progression, chronicity tended to progression, and the development of
      fibrocavernous tuberculosis. The morphological studies have provided evidence for
      the validity of the clinical and X-ray dynamics of the disease and for the
      correctness of choice of surgical policy.

PMID- 10067348
TI  - [Significance of radionuclide study in early diagnosis of chronic pleural
      empyemas].
AB  - Forty-five patients aged 17 to 70 years with exudative pleurisy were examined.
      Among them there were 31 patients with exudative pleurisy of tuberculous
      etiology, 7 with parapneumonic pleurisy and 7 with malignant pleurisy. In
      addition to clinical and X-ray examination, all the patients were studied for the
      functional status of the parietal pleura by using the radionuclide technique. The
      study indicated that the peripheral blood levels of radio pharmaceuticals (RP)
      ranged in relation to the duration of the disease: 0.33%, 0.31, 0.29, and 0.26%
      with a duration of 1-3, 4-6, 7-9, and over 10 months, respectively. With the
      least changes in the parietal pleura, the peripheral blood content of RP was
      highest and in pleural cirrhosis it was the lowest. The study showed that 66%
      were diagnosed as having early pleural empyema and 13 underwent pleurectomy.

PMID- 10067349
TI  - [Computed tomography in the diagnosis of intrathoracic lymph nodes tuberculosis
      in children].
AB  - Computed tomography (CT) was used to examine 48 children aged 3 to 14 years;
      among them 15 patients were studied for small tuberculosis of intrathoracic lymph
      nodes (ITLN), 33 for infiltrative and tumorous forms, 19 infected with
      Mycobacterium tuberculosis with progressive positive hyperergic tuberculin
      reactions or with its variations. Chest CT study of children with ITLN
      tuberculosis established the precise site of lymph nodal involvement, evaluated
      the lymph nodes based on their density, homogeneity, the presence of liquid and
      solid caseous portions, cavities, calcifications, and the affection of the
      adjacent mediastinal organs. CT data were used to make a differential diagnosis
      of bulky mediastinal formations regarded as ITLN tuberculosis. It is recommended
      to consider CT as the method of choice in the complex X-ray examination of
      children with ITLN tuberculosis.

PMID- 10067350
TI  - [Significance and role of radiation studies in complex diagnosis of exogenous
      allergic alveolitis].
AB  - The authors highlight X-ray symptom complexes (XRSC) (emphysematointerstitial,
      parenchymatointerstitial, and pneumonic) which are characteristic of exogenous
      allergic alveolitis (EAA). The above XRSC are comparable with the clinical types
      of EAA. The semeiotics typical of each XRSC and the value of radiation diagnostic
      methods in specifying changes in lung tissue and intrathoracic lymph nodes, the
      activity of the process are presented. Each study (classical X-ray, CT,
      radionuclide scintigraphy) has its own advantages and resolution limits.
      Radiation studies in the diagnosis of EAA should be used purposefully in
      combination with other studies (immunology, external respiratory function test,
      bacterial cytology, morphology) by taking into account the clinical
      manifestations of the disease.

PMID- 10067351
TI  - [Scintigraphic evaluation of pulmonary microcirculatory bed and intrathoracic
      lymph nodes in patients with infiltrative tuberculosis].
AB  - Complex radionuclide study was conducted in 134 patients with infiltrative
      tuberculosis. According to the extent and severity of a specific process in the
      lung, all the patients were divided into two groups. Group 1 comprised 43
      patients and group 2 included 91. Radionuclide studies were made according to two
      parameters: the activity of dysfunction of intrathoracic lymph nodes (ITLN) in
      the mediastinum with Ga-67 citrate and the magnitude of pulmonary regional
      circulatory disorders. The results of radionuclide studies in patients with
      infiltrative pulmonary tuberculosis indicated that not only a lung tissue
      inflammatory response, but also the development of pneumosclerotic changes both
      at the site of the basic specific process and in the intact area are responsible
      for regional circulatory disorders. The absorption uptake of Ga-67 citrate in the
      mediastinal lymph nodes and in the inflamed lung tissue areas varied with the
      process of chemotherapy and the beginning of a radionuclide study.

PMID- 10067352
TI  - [Radionuclide techniques in early diagnosis of pulmonary artery thromboembolism].
AB  - A combined procedure of indirect radionuclide phlebography and emission
      tomography of the lung with human serum albumin microspheres was employed to
      diagnose thromboembolism of pulmonary arterial branches (TPAB) and thrombosis in
      the inferior cava system. Four hundred and forty nine patients suspected for TPAB
      were examined. The data characteristic of pulmonary thromboembolism were obtained
      in 21.6% of cases. In 75 (17.6%) of 432 patients, indirect radionuclide
      phlebography revealed signs of thrombosis in the inferior cava at various sites.
      The radionuclide study of pulmonary perfusion is the only technique that assesses
      the degree of recovery of pulmonary perfusion after TPAB.

PMID- 10067353
TI  - [X-ray differential diagnosis of focal tuberculosis and peripheral lung cancer].
AB  - The paper deals with the differential diagnosis of focal tuberculosis and
      peripheral lung cancer. It presents data on 25 patients of whom 24 were
      misdiagnosed as having focal tuberculosis. The main reason for misdiagnoses was
      the similarity of early X-ray symptoms of the two diseases, namely, upper lobar
      site, increased and thickened lung pattern and focal shadows against this
      background. The most important differentially diagnostic criteria for the above
      diseases are varying optic densities of pulmonary structures at the site of
      involvement and different patterns of vascular changes in the lung portion with a
      pathological process.

PMID- 10067354
TI  - [Serological and immunochemical properties of carbohydrate-containing fraction
      from mycobacterium tuberculosis H37Rv].
AB  - Using affinity chromatography on concanavalin A (Con A) sepharose CL 6B, a
      carbohydrate-containing fraction was derived from Mycobacterium tuberculosis
      H37Rv sonicate. Surprisingly, the main component of Con A fraction was a protein
      having a molecular weight of a 30-kD range which is generally absent in the Con A
      adsorbed fraction from the culture filtrate. ELISA by means of an
      antimycobacterial monoclonal antibody panel showed that the 30-kD range of Con A
      fraction contained antigen 85. It is suggested that the derived components
      antigen 85 are a glycosylated form of the proteins associated with the
      mycobacterial cell wall. The Con A fraction, antigen 85 (Department of Virology,
      Pasteur Institute, Brussels, Belgium), and PPD (Batch RT 45, Stattens
      Seruminstitute, Denmark) were used for ELISA determination of antimycobacterial
      antibody titers in the sera of 30 patients with pulmonary tuberculosis, 28
      patients with nonspecific lung diseases (bronchitis and/or asthma, pneumonia), as
      well as in the sera of 12 healthy volunteers. The sensitivities were 46.42,
      57.34, and 72.33% and the specificities were 36.97, 26.73, and 56.75% for Con A
      fraction, antigen 85, and PPD, respectively. The authors suggest that
      serodiagnostic properties of Con A fraction are extremely limited.

PMID- 10067355
TI  - [Platelet activating factor in biological fluids of animals with different
      species-specific resistance at the stage of infective process after inoculation
      with mycobacterium tuberculosis].
AB  - Following 24 hours, 1, 2, and 6 weeks of inoculation of guinea-pigs and albino
      rats by Mycobacterium tuberculosis (MT), the levels of platelet activation factor
      (PAF) were determined in the plasma, leukocytes, alveolar macrophages,
      nonfractionated cellular sediment and fluid of bronchoalveolar lavage (FBAL) by
      testing rabbit platelets. The guinea-pigs developed generalized tuberculosis, the
      rats receiving a small dose of MT developed nonspecific inflammation and those
      taking a large dose had specific foci. In both experiments, spontaneous
      regression of inflammatory changes began in rats after 6 weeks. In the guinea
      pigs inoculated by MT, there was a steady increase in PAF synthesis in all cell
      populations, PAF levels dropped in fluids. In the rats receiving a small dose of
      MT, the cellular levels PAF levels periodically rose in early infection, but
      decreased below the control values during regression of inflammatory changes.
      Concurrently, the level of PAF became lower in plasma and FBAL. With high-dose
      inoculation, it drastically fell in the cells just after MT administration, then
      moderately increased during the development of specific changes and again dropped
      at the end of the experiment. In early infection the changes in PAF levels in the
      body's fluids were mirror as regards to the respective cells, but at regression
      of specific changes, the content of PAF was lower than the normal values in all
      the fluids under study.

PMID- 10067356
TI  - [Evolution of granulomas induced by BCG vaccine administered in the experiment].
AB  - The time course of hepatic granulomatosis was studied on a CBAxC57B1/6 murine
      model of a vaccinal process induced by BCG vaccine. It was found that over the
      natural course of inflammation, there were changes in the spectrum of granulomas
      from epithelioid cellular to macrophageal and fibrotic ones with stabilization of
      their sizes, averaged cellular composition and density in the organ. Long-term
      use of isoniazid caused a considerably (2-fold) reduction in the number of
      granulomas in the organ and thus a decrease in the level of its fibrotic process.
      Presumably, in the treated animals, the mechanism responsible for a reduction in
      the number of granulomas is the "dissociation" of macrophageal cells from them.

PMID- 10067357
TI  - [Tuberculous pleurisy].

PMID- 10067358
TI  - [Scientific conference on radiation studies and differential diagnosis in
      phthisiology and pulmonology].

PMID- 10067359
TI  - The effects of a fixed-fee reimbursement system introduced by the Federal
      Government on laboratory testing in the United States.
AB  - Rapid growth of health care expenditures during the 1970s in the United States
      led to implementation of a prospective payment system (PPS) based on diagnosis
      related groups (DRG) for Medicare inpatient reimbursement in 1983. With the
      introduction of DRG/PPS, hospitals encouraged earlier discharges and discouraged
      admission of patients who may require expensive services. Patient care has moved
      into more outpatient and non-hospital settings which have been less regulated and
      paid on a cost-reimbursement basis. The change of reimbursement system has
      converted hospital laboratories from "profit center" under the fee-for-service
      reimbursement practice to possible "cost center" at least for inpatient
      laboratory services with the advent of DRG/PPS. Hospitals have reduced laboratory
      operating expenses by constraining laboratory growth and development. Laboratory
      testing in non-hospital settings such as physicians' office laboratories, which
      were exempt from license and quality control by governmental regulations, has
      increased exponentially since implementation of DRG/PPS. To improve the quality
      of laboratory testing in such unregulated laboratories, the federal government
      has promulgated the Clinical Laboratory Improvement Amendments of 1988 (CLIA
      '88), requiring on-site survey and license under CLIA '88 for all laboratories in
      the United States regardless of the size, complexity, or location of laboratory.
      Implementation of DRG/PPS resulted in a temporary success in reducing Medicare
      Part A budget growth, but had only a small impact to slow the actual growth of
      total national health care expenditures or laboratory-related expenditures.
      Nevertheless, the change of reimbursement practice has created a large incentive
      to reduce unnecessary resource utilization, and cost-effective laboratory testing
      has become an essential concept during the DRG/PPS era.

PMID- 10067360
TI  - [Review and quality assurance of cytological follow-up cases of class III
      readings].
AB  - Standardization in diagnostic cytology remains limited. In this study, I reviewed
      laboratory reports which resulted in class III readings. Of 28,644 cytology
      specimens submitted between 1992 and 1996, a total of 1,335 (4.7%) were
      classified as class III. These class III cases were divided into eight groups;
      atypical cells in small number (I), low-grade atypical cells (II), combination of
      groups I and II (III), dysplasia (IV), unknown-origin cells (V), benign tumor
      cells (VI), degenerative cells by irradiation (VII) and poor fixation (VIII).
      More than half of the cases were from groups I, II and III. However, poor sample
      preparations (VIII) were found in 5.8%. Among the gynecologic specimens with
      class III readings, nearly 50% showed no malignancy by histological examination,
      but 28% exhibited carcinoma and the remaining 24% showed dysplasia. The results
      indicated that class III reports included a variety of findings from poor quality
      specimens to malignancy. At present, class III reports are regarded as a buffer
      zone by laboratories but cause misunderstanding among clinicians. Therefore, it
      is very important for laboratories to describe in detail why the specimen
      resulted in a class III reading.

PMID- 10067361
TI  - [Genetic alterations in human malignant tumor].
AB  - To clarify the genetic background of cancer patients, microsatellite instability
      (MSI) and mutations of transforming growth factor-beta type II receptor (RII),
      p53 and k-ras gene were investigated. MSI were detected in 33.3% of esophageal,
      15.8% of gastric, 21.4% of colorectal, 4.5% of bile duct, 0% of gallbladder,
      13.3% of pancreatic, 11.6% of breast and 10.5% of thyroid cancers. Mutations of
      RII gene were detected in only 2 of 9 MSI-positive colorectal cancers. k-ras gene
      mutations were investigated in colorectal, bile duct, gallbladder, breast and
      thyroid cancer and were detected in 11.9%, 36.4%, 64.3%, 0%, 0% of each. p53 gene
      mutations were investigated in colorectal and breast cancer and were detected in
      9.5% and 9.3%, respectively. In addition, 4 colorectal cancer cases exhibited
      more than two kinds of genetic alteration, while breast cancer cases showed only
      single kind. From these findings, it is suggested that 1) the incidence of each
      genetic alteration differed among the cancers investigated and organ specificity
      may exist; 2) the genetic alterations investigated here contributed to a minor
      part of cancer development, which requires the identification of more unknown
      genes related to carcinogenesis; 3) to clarify the molecular mechanism of cancer
      development, the genetic alterations including genomic instability and mutations
      of several kinds of genes related to cancer development in each case should also
      be determined along with their genetic molecular profile.

PMID- 10067362
TI  - [Present and prospects of telepathology].
AB  - Nearly ten years have passed since telepathology was introduced and real-time
      pathology consultations were conducted. Long distance consultations in pathology,
      cytology, computed tomography and magnetic resonance imaging, which are referred
      to as telemedicine, clearly enhance the level of medical care in remote hospitals
      where no full-time specialists are employed. To transmit intraoperative frozen
      section images, we developed a unique hybrid system "Hi-SPEED". The imaging view
      through the CCD camera is controlled by a camera controller that provides NTSC
      composite video output for low resolution motion pictures and high resolution
      digital output for final interpretation on computer display. The results of
      intraoperative frozen section diagnosis between the Gihoku General Hospital 410
      km from SRL showed a sensitivity of 97.6% for 82 cases of breast carcinoma and a
      false positive rate of 1.2%. This system can be used for second opinions as well
      as for consultations between cytologists and cytotechnologists.

PMID- 10067363
TI  - [Clinical autopsy evaluation].
AB  - The hospital autopsy rate in Japan dropped from 63.5 per cent in 1972 to 20.9 per
      cent in 1995. This reduction is attributable to declining interest by clinicians,
      surgeons and pathologists. The decline is a very serious problem, because the
      autopsy contributes to what has been called "quality control" of medical care.
      However, the method of autopsy should change along with advances in diagnostic
      technology or various changes in the circumstances surrounding medical practice.
      The most important problem at present is that autopsies require both time and
      effort. Delayed autopsy reports by pathologists may result in declined interest
      by clinicians and thus limit the benefits. To shorten the time delay for autopsy
      reports, clinicians must clarify their clinical questions concerning the deceased
      patient so that pathologists can readily identify the patients' problems and
      determine the causes more promptly, clearly and diplomatically. Other suggestions
      for improvement include the following: the reports should be simpler; the concept
      that all autopsies must be complete should be eliminated; a hospital accreditor
      must emphasize that clinicians intend to gain more precise diagnoses by obtaining
      post-mortem tissues of various organs using biopsy instruments. In addition,
      communication between pathologists and clinicians must be active to determine the
      pathogenesis of disease.

PMID- 10067364
TI  - [Genomic instability and neurodegenerative disease].
AB  - The discovery of unstable DNA sequences as the cause of genetic disease is a
      fascinating new area in human genetics, raising a number of important questions
      addressing the understanding of both the mechanisms and the effects of this new
      type of mutation. Trinucleotide repeat expansion mutations have been identified
      in a number of neurodegenerative diseases, including spinal and bulbar muscular
      atrophy (SBMA), fragile X syndrome (FRAXA and FRAXE), myotonic dystrophy (DM),
      Huntington's disease (HD), spinocerebellar ataxia types 1, 2, 3, 6, 7 (SCA1,
      SCA2, SCA3, SCA6, SCA7), dentatorubral-pallidoluysian atrophy (DRPLA),
      Friedreich's ataxia (FRDA) and autosomal dominant pure spastic paraplegia
      (ADPSP). They have been traced to genetic variation in the length of
      (CTG)n/(CAG)n, (CGG)n/(CCG)n, or (GAA)n/(TTC)n triplet repeats in DNA. In normal
      individuals these loci contain a short length of triplet repeats (usually 5-40),
      which is polymorphic within the population. Increases in the lengths of the
      translated triplet repeats to 40-100 are associated with disease symptoms,
      whereas the untranslated triplet repeats to 200-3000 are associated with the
      disease. We concentrated on repeat expansions in myotonic dystrophy. In this
      symposium, we outline the molecular aspects of myotonic dystrophy including DNA
      diagnosis and anticipation, and review the similarities and differences among
      these triplet repeat diseases.

PMID- 10067365
TI  - [Analysis of serum amyloid A1 alleles by PCR-RFLP].
AB  - Serum amyloid A1 (SAA1), the acute phase isotype of SAA protein family,
      preferentially forms amyloid fibrils in reactive amyloidosis. Three alleles
      (alpha, beta, gamma) have been identified in the SAA1 locus. A recent study
      suggested the association of SAA1 gamma with amyloidogenesis in Japanese patients
      with rheumatoid arthritis. In this study, PCR-RFLP method was developed for SAA1
      allele analysis. The use of two restriction enzymes, Ban I and Bcl I, for SAA1
      derived PCR products, clearly identified six SAA1 genotypes. The frequency of
      SAA1 alleles was determined in the 100 healthy subjects, and resulted in 33.0%,
      30.5% and 36.5%, for alpha, beta and gamma, respectively.

PMID- 10067366
TI  - [Small increases of the serum alkaline phosphatase activity and malignant
      changes].
AB  - In order to see the clinico-pathological significance of the small increase of
      serum alkaline phosphatase (ALP) activity alone in routine laboratory
      examinations, we picked up 76 new out-patients of adult within the two-fold high
      ALP level in contrast to the reference range in the Akita University Hospital for
      one year, and then studied the relation between the histories and serum ALPs of
      33 patients whose ALP had increased pathologically or decreased after
      intervention such as surgical operations. The ratio of the patients with
      malignant tumors to the tested all patients was 13 to 76 (17%). Immunochemical
      analysis of sera for the cancers of the lung, larynx and prostate showed that the
      small amount of the placental isozyme or intestinal-like isozyme was expressed
      selectively. It may be useful for earlier detection of malignancy to analyze the
      cancer-associated ALPs, when the small and sequential increase of the serum ALP
      activity is found in routine laboratory examinations.

PMID- 10067367
TI  - [A causal model of blood enzyme data and visualization of tissue conditions].
AB  - Quantitative diagnostics is an important field in which clinical data are
      converted into medical information. A variety of approaches to obtain medical
      diagnoses have been developed and multivariate statistical analysis supports the
      diagnostic process. Although many clinical data are affected by body conditions
      such as disease and functional failure, only a few models take this phenomenon
      into consideration. The correlation between laboratory test results can be
      understood as a causal relationship between body conditions and clinical test
      data variations. A multivariate statistical method, factor analysis, expresses a
      causal relationship between latent variables and observed variables. We developed
      a causal model for blood enzyme data using factor analysis. The latent variables
      were assumed to be organ specific regarding 9 enzyme data. This causal model
      expressed clinical knowledge within blood enzymes and allowed visualization of
      organ conditions. The visualization of laboratory data is useful to screen
      patient's pathological states.

PMID- 10067368
TI  - [Urinary excretion of steroid hormone and 3 beta-hydroxysteroid dehydrogenase
      activity in normal young adult women].
AB  - The urinary steroid hormone metabolites and the ratio of pregnenetriol (delta
      5P3) to pregnanetriol (P3) as indicators of 3 beta HSD activity in the urine of
      healthy young female were measured by means of capillary gas chromatography. All
      of the subjects have finished the normal pubertal development, and their adrenal
      steroid hormone secretion had reached to the stable state. We analyzed the
      diurnal variation, fluctuation during menstrual cycle and seasonal variation of
      delta 5P3/P3. We found that the hormone excretion in the urine of the morning
      during the follicular phase of menstrual cycle was relatively stable, and that
      the ratio of delta 5P3/P3 correlated highly with that in the total daily urine.
      In the seasonal variation, the urinary delta 5P3/P3 ratio in the subjects of high
      urinary DHEA group was relatively high, and that of the low DHEA group was low.
      Although the difference of delta 5P3/P3 ratio of the both groups was small, but
      statistically significant. Individual difference in the delta 5P3/P3 ratio was
      relatively small in comparison with that of the urinary DHEA excretion. About 5%
      of the all subjects showed marked high value of delta 5P3/P3 ratio. About 80% of
      the high urinary excretion group showed higher value than the average delta
      5P3/P3 ratio. These findings suggest that the normal young female subjects were
      divided into several groups with regard to the urinary DHEA excretion pattern and
      delta 5P3/P3 ratio in the urine. Both of them may be a specific individual
      marker.

PMID- 10067369
TI  - [Somatosensory evoked potential (SEP) to posterior tibial nerve stimulation in
      children with cerebral palsy].
AB  - We investigated the possible usefulness of SEP to the posterior tibial nerve in
      children with cerebral palsy. Sixty-four children with cerebral palsy, aged
      between 6 months to 20 years, were studied. Twelve patients had hemiplegia (H),
      24 spastic diplegia who were able to walk (SDW), 17 spastic diplegia who were
      impossible to walk (SDNW) and 11 spastic quadriplegia (SQ), respectively. We also
      studied with 40 normal controls. Informed consent was obtained from subjects and
      parents. A significant difference was found in an appearance rate of P37 between
      the control and cerebral palsy groups. Absent and shortening of P37 were
      recognized in 10 among 18 recordings in the paralytic side of patients with
      hemiplegia. The central conduction time was shortened gradually with age in the
      control group. There was difference in the central conduction velocity between
      SDW, SDNW or SQ. These results suggested that P37 was the first cortical
      response, and that it was useful for the diagnosis of cause of paralysis.

PMID- 10067370
TI  - [Congestive heart failure due to a combination of atrial fibrillation and
      tricuspid regurgitation: clinical course and echocardiographical analysis].
AB  - The combination of atrial fibrillation (Af) and tricuspid regurgitation (TR) may
      induce the congestive heart failure (HF) due to insufficient output. However,
      these associations have not been elucidated. We examined the clinical course with
      echocardiographic data in 119 patients with Af and/or TR and/or HF. Their mean
      age was 65 +/- 14 years. The patients were classified into 6 groups as follows:
      Group I contained patients with Af, TR and HF(n = 13); Group II contained
      patients with Af and TR, without HF(n = 59); Group III contained patients with TR
      and HF, without Af(n = 15); Group IV contained patients with TR and without AF
      and HF(n = 15); Group V contained patients with Af and HF, without TR(n = 24);
      Group VI contained patients with Af and without TR and HF(n = 13). The fractional
      shortening and ejection fraction in Group I and II were significantly (p < 0.05)
      decreased compared to Group IV. Moreover, the fractional shortening in Group V
      was significantly (p < 0.05) lower than in Group IV. Among 72 cases in Group I
      and II, 24 cases were followed by echocardiography for 2 to 5 years. Eight cases
      of HF exhibited a no HF state and 1 demonstrated had the HF state. All 9 cases
      (38%) showed a decreased heart rate and no alternation of TR. Four of the 24
      patients (17%) had developed worsened TR and a lowered ejection fraction but none
      developed them became HF. Therefore, tachycardia may be an accelerative factor
      for HF due to the combination of Af and TR, not due to the grade of TR.

PMID- 10067371
TI  - [What is your diagnosis? Transitory erythroblastopenia in childhood].

PMID- 10067372
TI  - [Anemia in pregnancy].
AB  - Pregnancy and postpartum anaemia occurs worldwide, particularly in developing
      countries where it accounts for substantial maternal and infant morbidity and
      mortality. The main cause is iron deficiency, primarily of dietary origin: 20% of
      the world population are estimated to have some degree of trace element
      deficiency. Even in industrialized countries iron deficiency anaemia is common in
      pregnancy due to the negative iron balance created by the high fetal demand for
      iron. It is compounded by blood loss during and after delivery, particularly in
      the absence of adequate prevention and treatment. The main effects of pregnancy
      and postpartum anaemia (defined by the WHO as hemoglobin values < 110 g/l and <
      100 g/l, respectively) present for the mother an increased susceptibility to
      infection and premature delivery and for the baby intrauterine growth retardation
      and the consequences of prematurity. Diagnosis and differential diagnosis are
      thus a major obstetric concern. Iron deficiency can be particularly difficult to
      diagnose in postpartum anaemia because ferrritin is often falsely elevated due to
      concurrent infection. Prevention with oral iron + folic acid supplementation has
      proven effective, as has intravenous iron in more severe cases, while the
      addition of recombinant erythropoietin augments the effect of iron alone.

PMID- 10067373
TI  - [Common anemias in neonatology].
AB  - We describe the four most common groups of neonatal anemia and their treatments,
      with particular emphasis on erythropoietin therapy. The hemolytic anemias include
      the ABO incompatibility (much more frequent, nowadays, than the Rh
      incompatibility, which has nearly disappeared following the use of anti-D
      immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G
      6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19
      predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the
      rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin
      transfusions, or during feto-maternal transfusions. Finally, the multifactorial
      anemia of prematurity develops principally as a result of the rapid expansion of
      the blood volume in this group of patients. Erythropoietin therapy, often at
      doses much higher than those used in the adult, should be seriously considered in
      most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of
      transfusions.

PMID- 10067374
TI  - [Treatment of anemia in chronic renal failure (predialysis)].
AB  - The treatment of renal anaemia with human recombinant erythropoietin (r-hu-EPO)
      in predialysis patients requires a close collaboration between the general
      practitioner and the nephrologist. This therapeutic option, along with other
      measures as part of the management of patients with renal insufficiency, is aimed
      at slowing down the progression of the kidney failure and at maintaining the
      patient in the best possible metabolic conditions. This paper summarises the
      benefits and risks of r-hu-EPO administered in renal insufficiency. The practical
      guidelines for the r-hu-EPO administration should help to assure an optimal and
      cost-effective utilization of the treatment.

PMID- 10067375
TI  - [Tumor anemia. Overview of the role of human recombinant erythropoietin (r-hu
      EPO) in treatment of tumor anemia].
AB  - The prevalence of anaemia in patients with cancer lies between 10 and 40%,
      depending on the type of tumor and chemotherapy. Anaemia has a significant impact
      on the quality of life, along with pain or disease progression. There are
      multiple causes but the physiopathology resembles that of inflammatory anaemia.
      The following mechanisms can be distinguished: a resistance of the erythroid
      precursor cells (BFU-e, CFU-e) to erythropoietin, an inappropriately decreased
      renal erythropoietin secretion for a given haemoglobin value and alterations of
      the iron metabolism leading to a functional iron deficiency. Recombinant human
      erythropoietin (r-hu-EPO) is safe and efficient in the treatment of anaemia of
      chronic renal failure and rheumatoid arthritis. In oncology different phase I and
      II studies have demonstrated an efficacy (increase of haemoglobin, decrease of
      transfusion requirements) in about 50% of all adult patients. A response to a
      subcutaneous r-hu-EPO treatment with a relatively high posology of 150 U/kg three
      times a week can be expected after one to two months. No single reliable
      parameter will predict a response to the r-hu-EPO treatment. Several phase III
      studies confirm that anaemia in cancer patients undergoing chemotherapy (notably
      with cisplatin) can be corrected in 40 to 60% of all cases and that the
      haemoglobin increase improves the quality of life. Finally, recent clinical
      trials suggest that an early r-hu-EPO treatment might prevent the occurrence of
      anaemia secondary to chemotherapy. Several parameters will have to be specified
      such as the precise definition of the groups at risk, the appropriate haemoglobin
      level to initiate a r-hu-EPO treatment, its optimal posology, as well as the role
      of the iron substitution and its route of administration. The impact of the r-hu
      EPO treatment on the quality of life of cancer patients constitutes a priority
      for future studies, which will have define the exact role of r-hu-EPO in oncology
      management.

PMID- 10067376
TI  - [Primary hyperparathyroidism].

PMID- 10067377
TI  - [94th annual meeting of the Japanese Society of Psychiatry and Neurology. May 20
      22, 1998. Okinawa, Japan. Abstracts].

PMID- 10067378
TI  - [94th annual meeting of the Japanese Society of Psychiatry and Neurology. May 20
      22, 1998. Okinawa, Japan. Abstracts].

PMID- 10067379
TI  - [94th annual meeting of the Japanese Society of Psychiatry and Neurology. May 20
      22, 1998. Okinawa, Japan. Abstracts].

PMID- 10067380
TI  - The utility of peak flow measurements in guiding asthma management--what is the
      evidence?

PMID- 10067381
TI  - Doctor under stress.

PMID- 10067382
TI  - Peak expiratory flow rate guided protocol did not improve outcome in emergency
      room asthma.
AB  - BACKGROUND AND AIMS OF STUDY: All current international practice guidelines
      recommend that treatment of acute asthma in the emergency room (ER) should be
      guided by the peak expiratory flow rate (PEFR). The aim of this study was to
      assess the efficacy of a PEFR guided protocol in treating ER asthma. METHODS: We
      compared two different management protocols in adult asthmatics who presented to
      the ER with acute exacerbations. The routine protocol (RP) assessed and dispensed
      patients according to overall subjective and clinical response without
      predetermined criteria. The peak protocol (PP) used serial measurements of PEFR
      to guide intensity of bronchodilator treatment and fitness for hospital
      discharge. On the PP, a threshold PEFR of > or = 60% predicted had to be achieved
      before the patient could be discharged from the ER. RESULTS: There were 79
      patients in the RP group and 70 in the PP group. There was no significant
      difference between the two groups in baseline PEFR, PEFR after treatment and
      percentage increase in PEFR with treatment. The PP resulted in a higher hospital
      admission rate than RP. CONCLUSION: We conclude that in the management of acute
      asthma in the ER, a PEFR guided protocol neither improved overall PEFR response
      to treatment nor reduced admission rates when compared with current management as
      it is practised in Singapore.

PMID- 10067383
TI  - Thrombocytosis in childhood.
AB  - INTRODUCTION: Thrombocytosis is a common condition in infancy and childhood.
      There are very few paediatric literature on its incidence and clinical
      significance. METHOD: We conducted a prospective study over 18 months (January
      1993 to June 1994) on all patients admitted with a platelet count done. Cases
      with platelet count > 600 x 10(9)/L were reviewed and followed-up. Serial
      platelet count were done at 1 week, 2 weeks, 3 weeks, 4 weeks, and then monthly
      until it normalised. RESULTS: One hundred and thirty-five cases out of 10,288
      admissions had raised platelet count. There was a preponderance of male (sex
      ratio M:F = 1.7:1). Majority was less than 1 year old. Seventy-eight percent had
      associated infection of which 2/3 were due to bacterial infections, Pneumonia was
      the most common bacterial infection associated with thrombocytosis whilst
      gastroenteritis was the most common cause for non-bacterial infection and
      Kawasaki's disease constituted the majority of the non-infective etiology. Cases
      with platelet count > 900 x 10(9)/L, 73.3% were due to bacterial infection. Three
      cases of Kawasaki's disease had platelet counts > 900 x 10(9)/L. Fifty-two
      percent of cases developed thrombocytosis within 4 days of illness. In
      nonbacterial infection, the thrombocytosis normalised by about 1 week after
      onset. For bacterial infection, the thrombocytosis normalised later depending on
      the severity of infection. In majority of the Kawasaki's disease, the platelet
      count normalised by the third week. CONCLUSION: Primary thrombocytosis is rare in
      paediatric age group. None of the cases developed any symptoms associated with
      thrombocytosis. Secondary thrombocytosis is a benign and common phenomenon in
      children.

PMID- 10067384
TI  - Telephone counselling in psychiatry.
AB  - AIM OF STUDY: To study the description of callers using a telephone helpline to
      improve support to patients in between appointments. METHOD: This includes
      creating a helpline in the department and getting psychiatrists, medical
      officers, psychologists and social workers trained to man this line during office
      hours. Information from callers were recorded and analysed using SPSS for MS
      Windows version 6.0. RESULTS: The callers were mainly females calling about
      personal problems, namely psychiatric symptoms and sleep difficulties. Half were
      given specialist appointments and one-fifth were discharged after telephone
      counselling. CONCLUSIONS: Telephone counselling is useful in clarifying medical
      instructions and supporting psychiatric patients in between outpatient
      appointments.

PMID- 10067385
TI  - Laparoscopic adhesiolysis for subfertility.
AB  - AIM: Laparoscopic adhesiolysis has been associated with pregnancy rates of 12% to
      58%. This study looks at our experience with laparoscopic adhesiolysis in the
      management of subfertile patients. METHOD & RESULTS: Between January 1992 and
      March 1995, 27 subfertile patients who had laparoscopic adhesiolysis done were
      studied. Four patients (15%) had a second look laparoscopy. The overall pregnancy
      rate (after excluding 6 patients with bilateral tubal blockage or severe male
      factor) was 33% (7/21). The take home baby rate was 14.3% (3/21) and the ectopic
      pregnancy rate was 4.7% (1/21). CONCLUSION: Laparoscopic adhesiolysis still
      remains a useful and effective procedure for infertile couples with pelvic
      adhesions.

PMID- 10067386
TI  - The prescribing pattern of hospital doctors.
AB  - OBJECTIVE: There has been no local data on the prescribing habits of doctors over
      the last 25 years. This is a retrospective study done to examine the outpatient
      prescribing pattern of doctors at Alexandra Hospital over a one month period in
      1995. METHOD: Six-thousand five-hundred and three scripts were analysed. A total
      of 16,642 items were prescribed. The distribution of prescription scripts by
      departments included Accident & Emergency 39.0%; Medical 23.5%; Orthopaedics
      10.3%; Surgery 18.5%; Paediatrics 4.4%, and Geriatrics 4.3%. The overall mean
      number of drugs prescribed was 2.6 (median = 2, mode = 2, range = 14). RESULTS:
      Analysis of the overall results by age groups showed the following means for
      "total number of drugs prescribed": (> 0 to 20 years) = 2.23, (> 20 to 40 years)
      = 2.42, (> 40 to 60 years) = 2.61 and (> 60 years) = 3.18. Analysis of variance
      showed highly significant results between the means of each age-group. Post-hoc
      analysis revealed that the oldest age group (> 60 years) accounted for most of
      this significant result. The top 10 drugs used by the hospital were (in
      descending order): NSAIDs, antacids, analgesics (other than NSAID), antibiotics,
      topical medications, anti-diarrhoeal agents, anti-histamines, vitamins, anti
      emetics and promethazine cough syrup. There was a high usage of NSAID-antacid
      combination. Similarly, amoxycillin was often given with cloxacillin. There was
      an underuse of anti-depressants. There were very few (0.15%) illegible
      prescriptions. Only one prescription had an adverse combination of drugs.
      CONCLUSION: This is the first local study of prescribing pattern of a hospital.
      While this data may vary from hospital to hospital, depending on the patient mix,
      it does provide some useful baseline data which hitherto never existed. Our
      findings suggested that the elderly do receive more medications.

PMID- 10067387
TI  - Haematuria clinic--a preliminary audit and considerations for a one-stop
      assessment centre.
AB  - AIM: To audit and study the practicality of an integrated Haematuria Clinic as a
      one-stop assessment centre for the investigations of patients presenting with
      haematuria. METHODS: A weekly clinic was organised to facilitate consultation,
      intravenous urogram and flexible cystoscopy for patients with haematuria. A
      protocol was set up and data on symptoms, types of haematuria, results of the
      investigations and outcomes were collected. RESULTS: About half of all the
      patients seen in this clinic were found to harbour urological lesions; of which
      urolithiasis (20.4%) and urological malignancies (14.2%) were the most common
      lesions identified. Transitional cell carcinoma of the bladder was the most
      common malignancy diagnosed (8%). Significantly, 2 of 9 (22.2%) bladder cancers
      were found on cystoscopy and missed on the cystogram phase of the intravenous
      urogram. Ten urological lesions would have been missed if cystoscopies were not
      performed. Conversely, in 14 patients, cystoscopy could be avoided because their
      intravenous urograms identified lesions sufficiently to allow for definitive
      treatment. CONCLUSIONS: The need and types of investigation for patients with
      haematuria are evolving. We recommend intravenous urogram and flexible cystoscopy
      as the standard investigations and caution against ignoring microscopic
      haematuria. These assessments can be organised into an integrated clinic
      improving deliverance of clinical care; which may result in better patient
      compliance for investigations and earlier detection and treatment of urological
      lesions presenting as haematuria.

PMID- 10067388
TI  - Pseudo myocardial infarct--electrocardiographic pattern in a patient with
      diabetic ketoacidosis.
AB  - Diabetic ketoacidosis is an extremely serious complication of diabetes mellitus.
      It arises because of a complex disturbance in glucose metabolism. There is
      usually a precipitating cause such as sepsis or myocardial infarction. If not
      recognised and appropriately treated, it can have devastating consequences. This
      is a case report of a patient with severe diabetic ketoacidosis and interesting
      electrocardiographic findings. The initial electrocardiographic (ECG) findings
      were suggestive of an acute myocardial infarction. The ECG changes normalised
      remarkably following initial management of the diabetic ketoacidosis. There have
      been only occasional reports of hyperkalemia causing electrocardiographic
      changes, closely resembling those of acute myocardial infarction.

PMID- 10067389
TI  - Takayasu arteritis--a case report of aortic aneurysm.
AB  - Aortic pseudo-aneurysm is a rare manifestation of Takayasu arteritis. We present
      a 16-year-old girl who first complained of multiple arthritis, recurrent
      abdominal pain and malaise at the age of 15 years. The initial working diagnosis
      was juvenile rheumatoid arthritis. Follow-up abdominal ultrasonography for her
      hepatomegaly incidentally revealed an aortic aneurysm. Total aortography showed
      diffuse aortic narrowing and an infra-renal aortic pseudo-aneurysm. Vascular
      reconstruction with an interposition Dacron graft was performed with uneventful
      recovery. Early non-specific presentation of Takayasu arteritis often results in
      delay of diagnosis. The presence of a vascular bruit in a young female with non
      specific symptoms should point to a differential diagnosis of Takayasu arteritis.
      We review the role of surgery in the management of this condition.

PMID- 10067390
TI  - Potassium and anaesthesia.

PMID- 10067391
TI  - What you need to know: how to manage your stress.

PMID- 10067392
TI  - What you need to know: guidelines to medical practitioners for proper maintenance
      of drugs and dispensing records (including controlled drugs).

PMID- 10067393
TI  - The training of future doctors.

PMID- 10067394
TI  - Medical education revisited.

PMID- 10067395
TI  - What makes a good doctor--views of non-medical professionals.

PMID- 10067396
TI  - Reflection for young doctors and doctors of tomorrow.

PMID- 10067397
TI  - 'What makes a good doctor?'--views of the medical profession and the public in
      setting priorities for medical education.
AB  - AIM: The concept of the 'good doctor' was systematically studied by determining
      the view of doctors and non-physicians regarding the qualities and attributes of
      an ideal physician. METHOD: A list of characteristics of a good doctor was
      compiled from a Medline search, and from opinions generated by three focus groups
      (medical school academics, general practitioners and non-medical professionals).
      This was qualitatively categorised into five domains: 1. Cognitive, 2. Conative,
      3. Emotional, 4. Interpersonal, and 5. Moral-ethical. An inventory comprising 25
      statements, which reflected the most commonly and consistently identified
      characteristics was administered to 274 doctors and 400 members of the public.
      Each item was scored on a Likert scale (0 = not important, to 4 = absolutely
      essential). RESULTS: The public regarded being 1. knowledgeable and 2. keeping up
      to-date most important; physicians regarded being 1. honest and 2. responsible
      and trustworthy as the two most important items. There was significant difference
      (p < 0.001) between physicians 'and the public' item ratings for 13 of the 25
      items. The public rated cognitive qualities most highly; the ethical domain was
      most important to doctors. Healthcare consumers were significantly more concerned
      than doctors about domains of emotional regulation, and communication. Overall,
      the two groups had strong agreement on the rank order of both items and domains
      (Spearman r, 0.88 and 0.91). CONCLUSION: Medical education should inculcate the
      values and qualities desired by both the medical profession and public. Basic
      medical knowledge and reasoning are of prime importance; moral-ethical issues and
      communication skills should also be emphasised. Selection criteria for admission
      to medical school should also consider humanistic, non-cognitive traits.

PMID- 10067398
TI  - Experience with portfolio-based learning in family medicine for master of
      medicine degree.
AB  - BACKGROUND: The Private Practitioners Stream (PPS) of the Family Medicine
      Traineeship Programme for the Master of Medicine (Family Medicine) (MMed (FM))
      was started in 1995. The portfolio-based learning approach was used as the staple
      learning method in the tutorial system. Due to the autonomy given to Family
      Medicine trainees in choosing the topics for the portfolio-based presentations,
      the completeness of coverage of the Family Medicine training syllabus is a
      research question. AIM: To study if portfolio-based presentations in a tutorial
      system covered the broad based Family Medicine training syllabus. METHOD: Data in
      the one-page portfolio-based records developed were used to categorise the
      presentations according to the topics in the Family Medicine Modular Course.
      RESULTS: In the three-year period since the introduction of the PPS, 83 tutorials
      were conducted in which 87 portfolio-based presentations were made. Thirteen
      (15%) were in the Whole Person Medicine category, 70 (80%) in the Disease
      Management category and 4 (5%) in the Practice Management category. CONCLUSION:
      The portfolio-based learning is recognised as useful in continuing medical
      education because of the autonomy it gives to the adult learner. In our three
      years' experience, the one-page portfolio-based record developed was effective as
      the staple learning tool to cover the broad range of topics required in the
      defined syllabus of training and to meet the focus of the MMed(FM) examination.

PMID- 10067399
TI  - The Mitchell distal metatarsal osteotomy for hallux valgus--the Singapore General
      Hospital experience.
AB  - BACKGROUND: Fifty-five Mitchell distal metatarsal osteotomies for hallux valgus
      performed over a period of four years have been retrospectively reviewed. The 38
      patients were followed for an average of 30 months (range 12 to 60 months).
      RESULTS: The preoperative hallux valgus angle averaged 30.9 degrees +/- 8.2
      degrees SD (range 18 degrees to 60 degrees) and the postoperative angle averaged
      12.2 degrees +/- 4.6 degrees (range 5 degrees to 20 degrees). CONCLUSION: Ninety
      two percent of the patients were satisfied with the result of the procedure. They
      stated that, given the identical situation, they would undergo the operation
      again.

PMID- 10067400
TI  - Breastfeeding at 6 months and effects on infections.
AB  - AIMS: To examine the pattern of and the influence of some socio-demographic
      factors on infant milk feedings, and the protective role of breastfeeding against
      infections. METHODS: Mothers who breastfed their infants (exclusively or
      partially) at 6 weeks postpartum, and who had singleton pregnancies and healthy
      infants at birth, were interviewed when their infants had reached 6 months of
      age. RESULTS: Of the 234 mothers studied, only 31 (13%) mothers were practising
      exclusive breastfeeding (EBF) and 133 (57%) mothers were using exclusive infant
      formula feeding (EIF). Solid and semi-solid foods were introduced between 4 to 6
      months of life in 89% of the infants. On logistic regression analysis, mothers
      who were in paid employment [OR 0.25, 95% CI 0.15, 0.42] and not breast feeding
      at 6 weeks [OR 0.32, 95% CI 0.19, 0.54] had decreased odds of EBF. Antenatal
      plans to breastfeed, breast-feeding difficulties, ethnicity, level of parental
      education, parental ages, fathers' income, primigravida status and infants'
      gender were not significant co-variates. In comparison, EIF was more likely in
      mothers who worked, practised mixed feedings at 6 weeks and of Chinese descent.
      There were no significant differences in the rates of upper respiratory tract
      infections (URTI) or diarrhoeal illnesses between the infants who were or were
      not being breast-fed. CONCLUSIONS: Most mothers were unable to breastfeed their
      infants exclusively in the recommended first 4 to 6 months of life. Complementary
      changes outside the hospital and maternity services are essential in improving
      breastfeeding rates. Breastfeeding does not appear to confer significant
      protection to either URTI or gastrointestinal tract infections.

PMID- 10067401
TI  - Ophthalmic manifestations in Asian patients with systemic lupus erythematosus.
AB  - AIM OF STUDY: To determine the spectrum and prevalence of ophthalmic
      manifestations of systemic lupus erythematosus (SLE) in Asian patients. METHODS:
      We performed a standardised ophthalmic examination on consecutive Asian patients
      with SLE referred from a tertiary rheumatology unit to an ophthalmology
      department. RESULTS: Seventy patients were included in the study. There were 66
      females (94%) and 4 males (6%). The mean (range) age of the patients was 32.9 (9
      67) years. Five patients (7%) had ophthalmic symptoms while 65 (93%) were
      asymptomatic. Eighty-three eyes of 45 patients had abnormal Schirmer's #1 test
      and 27 of these eyes of 17 patients also had concomitant rose bengal staining of
      the cornea and/or conjunctiva. Seventeen eyes of 9 patients had retinal vascular
      lesions. Fourteen of these eyes had mild microangiopathic retinopathy with best
      corrected visual acuity (BCVA) 6/12 or better and 3 had retinal vaso-occlusive
      disease with BCVA worse than 6/12. Twenty-eight eyes of 14 patients had cataract
      and 3 eyes of 2 patients had raised intraocular pressure. Twelve eyes of 7
      patients had BCVA worse than 6/12 because of optic neuropathy (4 eyes), posterior
      subscapsular cataract (4 eyes), retinal vaso-occlusive disease (3 eyes) and
      phthisis bulbi (1 eye). None had any eyelid lesion, extraocular motility disorder
      or retrochiasmal disorder of vision. CONCLUSIONS: Asymptomatic dry eye is the
      most common ocular finding in patients with SLE. Sight-threatening complications
      of SLE include retinal vaso-occlusive disease and optic neuropathy.

PMID- 10067402
TI  - Experience of percutaneous endoscopic gastrostomy at Massachusetts General
      Hospital--indications and complications.
AB  - BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) is a relatively new method
      to deliver nutrition to patients with inadequate caloric intake who have a
      functionally intact gastrointestinal tract. METHODS: This is a retrospective
      review of 58 consecutive patients who were referred to the Surgical Endoscopy
      Unit, Massachusetts General Hospital for placement of PEG in 1996. The current
      indications, methods, and results of PEG will be discussed. RESULTS: Of this
      series, all but one patient had the PEG successfully placed. Indications included
      head and neck cancer (29 patients); neurological disorders (21 patients); burns
      (3 patients); respiratory failure (2 patients), and aspirations (2 patients).
      Fifty-four percent of cases were performed with local anaesthesia. There was one
      complication (2%) with no procedural-related mortality. CONCLUSION: PEG is an
      easy and safe procedure. It is a good alternative to provide enteral feeding in
      selected patients.

PMID- 10067403
TI  - The death of Sir Thomas Stamford Raffles (1781-1826).
AB  - The authors reviewed a rare autopsy report of Sir Thomas Stamford Raffles and
      offer a fresh interpretation of the cause of his death, with illustrations on the
      implied findings.

PMID- 10067404
TI  - [The comparative characteristics of chemically and light-hardened composite
      materials in vitro].
AB  - The strength and color stability of various composites of photo- and chemical
      consolidation is assessed by laboratory methods. The class of a material is the
      most essential factor affecting the above characteristics. The macrofilled and
      hybrid materials showed the best adhesive and bending strength. The method of
      consolidation does not notably affect the studied characteristics.

PMID- 10067405
TI  - [Changes in the quantitative composition of the microbial flora of dental
      deposits during the intensification of oral hygiene].
AB  - The efficacy of hygienic treatment of the oral cavity in combination with ozone
      therapy is assessed. This combination mechanically removes soft dental deposit
      and decreases bacterial contamination.

PMID- 10067406
TI  - [The use of antihomotoxic therapy in dentistry].
AB  - Efficacy of traumel C is assessed in patients with various maxillofacial
      inflammations. Sixty-nine patients with diseases of the buccal mucosa (aphthous
      stomatitis, herpes labialis, and perleches), periodontal tissues, and painful
      syndrome after dental canal filling were treated. Applications of the drug were
      administered to patients with diseases of the buccal mucosa and slight or medium
      severe periodontitis. Patients with grave periodontitis and pain after dental
      canal filling were injected with traumel solution. Positive shifts were attained
      in all cases. The duration of treatment depended on the process severity. The
      results recommend traumel C as an ointment for local applications and an
      injection solution for combined therapy of diseases of the buccal mucosa and
      periodontitis. The treatment schemes are convenient for outpatient treatment;
      there are no contraindications precluding the drug use. No side effects were
      observed.

PMID- 10067407
TI  - [The determination of the tooth-destroying loading while clamping the forceps
      during tooth removal].
AB  - The research results of the fracture load under the fixation of the dental
      forceps in vitro on the fresh extracted teeth are presented. The data analysis
      shows that the probability of the teeth fracture depends their clinical state and
      mechanical properties. It is practically impossible to fracture the intact and
      minor caries teeth by forceps at the first loading.

PMID- 10067408
TI  - [The prediction of the outcomes of severe odontogenic inflammatory diseases of
      the maxillofacial area taking into account biorhythms].
AB  - Time course of laboratory parameters is assessed in 31 patients with severe
      maxillofacial inflammations, hospitalized in intensive care wards. The patients
      were followed up for 4 to 42 days. Routine blood and urine analyses were
      monitored. Wave-like fluctuations in all laboratory parameters with periodicity
      of about a week (biorhythms) were detected. In lethal outcomes, the rhythms were
      disordered (desynchronized) and counterphases were detected. A grave course of
      inflammation is for the first time graphically represented critical periods of
      the diseases are determined; this will help planning the rational terms for
      monitoring the homeostasis, predict the disease outcome, and improve the
      treatment of such patients.

PMID- 10067409
TI  - [The pharmacokinetics of lincomycin when used as a component of a drug
      combination with ultrahighly dispersed hydroxyapatite].
AB  - A drug composition LINCOGAP is assessed, consisting of lincomycin hydrochloride
      (33%), ultrahighly dispersed hydroxyapatite (HA) (33%), gelatin (7%), and water
      (27%). Distribution of tritium-labeled lincomycin in organs and tissues of
      experimental animals was studied by the radiometric method after implantation of
      the composition into a standard rat mandibular defect. Lincomycin concentration
      surpassing by orders of magnitude the minimal inhibitory concentration for the
      main lincomycin-sensitive microorganisms persisted at the site of implantation of
      the composition for at least 7 days, while the concentration in internal organs
      and tissues was the minimum. Microbiological findings indicate active diffusion
      of lincomycin from the site of injection into the adjacent bone. Thus, LINCOGAP
      exerts an antibacterial effect in the pathological focus while its general toxic
      effect is low and, therefore, side effects are minimized. Combination of the
      antibiotic with ultrahighly dispersed HA helps regulate the process of bone
      repair, stimulating the proliferative and functional activity of osteoblasts.
      Hence, combined drug LINCOGAP is a promising agent for the treatment of
      inflammatory destructive diseases of osseous tissue.

PMID- 10067410
TI  - [The optimization of the reparative processes in a mandibular bone wound in
      patients with chronic alcoholism].
AB  - A total of 148 chronic alcoholics with mandibular fractures were treated.
      Hydroxyapol and colapol were inserted in bone wounds for improving the reparative
      osteogenesis. Clinical, immunological, and echo-osteometric data demonstrated the
      efficacy of both preparations, which promoted bone repair and reduced the
      incidence of pyoinflammatory complications.

PMID- 10067411
TI  - [The characteristics of the immune status of patients with combined jaw
      deformities before and after an osteotomy operation on the maxillary complex].

PMID- 10067412
TI  - [The use of titanium mesh plates for graft fixation in mandibular osteoplasty].
AB  - Opportunities of the use of mesh titanium plates as fixing devices are considered
      at reconstruction operations. Data of following up 8 patients with defects of the
      mandible of various location and extent are analysed. They were operated with
      reconstruction of the mandible with iliac graft and bone graft fixing with the
      mesh titanium plates. A technique of the operations is described, a case of
      successful use of mesh titanium implant modelled by the form of the mandible in
      repair of the mandible defect. The analysis of long-term results shows the
      potential efficiency of the use of mesh titanium plates as fixing adaptations in
      bone plastic operations.

PMID- 10067413
TI  - [Surgical treatment methods for the short saddle nose and high skin portion of
      the upper lip].
AB  - Remote results of treatment are analyzed in 10 patients with deformations of the
      nose combining a shortened nose and pulled in skin of the septum. The patients
      were operated on according to Burian. Good results were obtained in 4 cases,
      satisfactory in 5. A higher share of satisfactory results of Burian's operation
      is explained by the fact that it is very difficult to draw down the thick porous
      skin into a proper position, particularly at the tip of the nose. Additional
      operations are needed, deteriorating the cosmetic effect. The method proposed by
      the authors yields better results: 89% good and 16% satisfactory. The
      intervention is aimed directly at removal of the deformation and tissue defect.
      Mutual transposition of three flaps, one of which is a drawn columella and two
      other flaps from the upper lip fill the mucosal defect, repairs the pulled in
      skin part of the septum and elongates the tip of the nose. In addition,
      transposition of skin flaps from the upper third of the upper lip to the site of
      mucosal defect shortens the height of the upper lip, thus creating a correct
      proportion of the middle and lower thirds of the face.

PMID- 10067414
TI  - [Enhancing the esthetic properties of fixed dentures].

PMID- 10067415
TI  - [A biomechanical study of dental implants using a method for 3-dimensional
      volumetric mathematical modelling].
AB  - Biomechanics of the dental implants introduced into alveoli immediately after
      tooth extraction has been investigated. The programme ANSYS has been used. Three
      dimension volume mathematical models were calculated, with the help of which the
      tense-deformed state of the supportive biological tissues has been investigated
      in the area of direct implantation. On the grounds of the results obtained a
      conclusion has been made that there is an essential improvement of the load
      distribution under investigation of the inner bone modified biologically designed
      implants for direct implantation.

PMID- 10067416
TI  - [Microwave technology for fabricating the bases of plate dentures].
AB  - Polymerization of basic acrylic heat-hardened plastic under the effect of UHF
      exposure is studied. Specimens and standard bases of dentures from Russian
      acrylic plastic widely used in orthodontics were used in experiment. Plastics
      polymerized in UHF field and in water bath were compared. Experiments helped
      develop a method for making removable dentures using microwaves.

PMID- 10067417
TI  - [The automation of the processing and interpreting of teleroentgenograms].
AB  - Demonstrates the advantages of computer preparation of teleroentgenograms (TRG)
      and their layout and deciphering for subsequent roentgenocephalometric analysis.
      Using a full-page scanner, TRG is recorded in a computer, which improves the
      image by transforming the histogram brightness and then superimposes this image
      on the contour of the initial image. The quality of layout is improved by a
      larger (at least two times) image on the monitor and anthropometric points marked
      strictly parallel to the abscissa and ordinate. All this 50 times improves the
      accuracy of measurements on the prepared TRG and thus increases the value of
      roentgenocephalometric analysis.

PMID- 10067418
TI  - [The choice of the optimal plan for treating dystopia of individual teeth
      combined with arch defects of the maxilla].
AB  - Treatment of patients requires cooperation of an orthodontist and prosthesis
      maker as early as during treatment planning. An adequate clinical situation of
      treatment can be chosen only after preliminary modeling and prediction of results
      using dismountable diagnostic models of the jaws and computer simulation of the
      graphic scheme of the teeth position and transposition, described in this paper.
      Two-staged orthodontic and orthopedic treatment is needed for patients with early
      removed teeth and delayed prostheses, congenital cleft alveolar process and
      palate, and lack of two lateral incisors. However, for 25% of patient lacking two
      lateral incisors, orthodontic treatment alone is sufficient.

PMID- 10067419
TI  - [Commercial outpatient-polyclinic dental care for the population].
AB  - The authors have analysed annual activity of the dental clinic. On the grounds of
      the analysis they have formulated principles that can help commercial dental
      services to become a highly effective part of general medical aid to population.
      The principles are: highly skilled surgical (periodontological), therapeutic,
      orthopaedic aid in cooperation and specialisation in accordance with generally
      adopted staff standards; complex of periodontological aid; modern medicines and
      filling materials. Statistical data on each dental manipulation requirement in
      the conditions of commercial dental clinic are provided.

PMID- 10067420
TI  - [The immediate and late results of using the Scalpel-1 laser unit].
AB  - Efficacy of treating tumors of the face and buccal mucosa with a laser scalpel is
      analyzed. A total of 455 patients of both sexes aged 9-55 years were treated.
      Scalpel-1 device was used. 185 patients operated on from December 1, 1991 to
      December 1, 1996 were followed up for 5 years. No relapses occurred and a good
      local cosmetic effect was attained.

PMID- 10067421
TI  - [Medical informatics in the training of students, dentists and teachers in dental
      schools].
AB  - Philosophy of training students, physicians, and tutors of dentistry schools in
      medical informatics and the relevant curricula are discussed. Specialized
      software for differential diagnosis and treatment of the major stomatological
      diseases (dental caries, pulpitis, periodontitis, mucosal, periodontal, oral
      diseases, tumors, rapid methods for AIDS screening, etc.) are presented.

PMID- 10067422
TI  - [A universal computerized training system for the instruction in computer
      technologies of dentists, students and teachers in dental schools].
AB  - A complex of equipment for computer technology training is described. Its three
      main blocks are technological (Server, Smart), automated working place (AWP) for
      head physician (tutor), and AWP for a dentist. The complex works in the Power
      Line and Ulter-Line operation network in the network and autonomous modes.
      Methods of training students, dentists, and tutors of dentistry schools are
      described.

PMID- 10067423
TI  - [Assessing quality in the conducting of seminars for the advanced training of
      dentists].
AB  - Regular analysis of questionnaires distributed among students of self-supporting
      workshops carried out at the Training Center is aimed at elucidating the
      students' opinions about organization of workshops in order to optimize it and at
      collection of marketing information on the training and medical activities of the
      firm. The majority (90%) of respondents gave a positive answer to the question:
      "Will you advise your colleagues to go to workshops at the Training Center?"
      Exhibitions of materials offered by the firm and training of students to use
      these materials demonstrate the advantages thereof. Analysis of questionnaires
      showed that just a little part of dentists know the true price of their work and
      that the major part of the market of dental service is oriented, judging by the
      proposed costs, mainly at the solvent population.

PMID- 10067424
TI  - ["The honor of being right": Experiment and theory in the dispute over the
      doctrine of irritability].
AB  - In the middle of the 18th century the leading physiological concepts shift from
      mechanism to vitalism. The turning point of this change is Albrecht von Haller's
      Dissertation on the irritable parts (1752/53). The decisive discussion about
      irritability takes place between strictly empirical Hallerians and their
      opponents who try to build new medical systems on this property. Hence, the
      debate is also about experiment and theory. The 'sociology of scientific
      knowledge' furnishes models and theories that help us to conceive the
      argumentations and strategies of the leading figures. Thus, we understand why
      even Haller--the 'founder of modern experimental physiology'--has to allow
      general conclusions and to support vitalistic interpretations if he wants to
      succeed with some of his views. Only in its modified form the 'Irritabilitas
      Halleriana' meets the interest needed for dissemination.

PMID- 10067425
TI  - Getting the point; Paul of Aegina on arrow wounds.

PMID- 10067426
TI  - [Derangement of the mind in the Paracelsus tract "Liber de lunaticis
      Theophrasti"].
AB  - In a treatise "Liber de lunaticis Theophrasti" Paracelsus describes his view of
      "lunatici". These are men, inflicted by a psychopathological process, that
      gradually destroys their minds. He develops his argumentation on the base of
      iatroastrological, new-neoplatonistical and Christian thoughts. In his view man
      is a microcosm in macrocosm and a trichotomically organized being. Man is
      influenced by three lights. These lights are representing three levels of
      vitalisation, knowledge and cognition. According to this, man consists of the
      body (corresponding to the level of visible material light), the soul
      (corresponding to the invisible astral-sidereal light of the firmamental
      macrocosm) and the spirit (corresponding to the light of Christ and the divine
      Christian sphere of spiritual light). The origin of lunatic confusion of the mind
      is caused by the intrinsically motivated intention of man (representing the
      microcosm) to shift his spiritual focus from the protective sphere of spiritual
      light to the sphere of astral-sidereal macrocosmic emanations. The latter have a
      deteriorative influence on man's mind, due to the lack of guidance of man's
      consciousness by the spiritual light. Paracelsus describes the individual and
      sociological effects of lunatic confusion. These effects may range from personal
      confusion up to the aggregation of lunatics in ideologically coordinated groups
      of fanatics, displaying wrong teachings, dissensions and even warfare and
      homicide. Concerning the therapy of "lunatici" Paracelsus develops ideas, which
      show a resemblance towards integrative and holistic tendencies of our days
      discussed in the field of Psychoanalysis, Behavioral Medicine and "Holistic
      Health Medicine". In general the Paracelsian concept of lunatic deterioration can
      be regarded as an historic example that deals with an integrative approach
      towards the description of psychiatric disorders.

PMID- 10067427
TI  - [De-professionalization or 'para-professionalization'?. The professional
      development of the midwife and her place in the obstetrics of the 19th century].
AB  - The present article deals with the standing and the tasks of midwives in 19th
      century Wurttemberg. After outlining the legal framework of obstetrics, special
      emphasis was given to the education and activities of contemporary midwives, and
      to their numbers. At the beginning of the 18th century, obstetrics was almost
      exclusively in the hands of women. After 1800, a growing number of barber
      surgeons and physicians began to practise obstetrics. At the same time,
      vocational training and qualification of women-obstetricians increased
      considerably. Schools for midwives and lying-in hospitals were founded. In these
      schools a limited number of midwives were trained by physicians. Finally a
      hierarchy of different groups of obstetricians developed: first physicians, then
      barber-surgeons, midwives and folk healers. Although midwives were more or less
      excluded from operative obstetrics and high-risk-pregnancies, care and
      supervision of uncomplicated pregnancies, and of women in childbed remained their
      responsibility. It could be shown that in 19th century Wurttemberg more than 90
      percent of pregnancies ran a safe course, and neither physicians nor barber
      surgeons took a special interest in the care of normal births. Thus there was no
      dramatic transfer of obstetric care from the hands of the midwives to those of
      academically trained men. The high social status of the university-bred
      physicians separated them from most of the patients, as did the doctors' high
      fees. A certain indolence, and a remarkable sense of shame on the part of the
      pregnant women prevented much demand for academic obstetricians.

PMID- 10067428
TI  - [Discovery and development of donepezil hydrochloride for the treatment of
      Alzheimer's disease].
AB  - The most consistent change of neurotransmitter in the brain of Alzheimer's
      patients is the dramatic decrease of cholinergic innervation due to the loss of
      neurons in the basal forebrain. The most widely studied acetylcholinesterase
      inhibitors (AChEIs) have been physostigmine and tacrine. Physostigmine has very
      short duration, and tacrine has liability to hepatotoxicity. These are the
      defects of the inhibitors. Our objective was to find a new type of AChEIs that
      would overcome the disadvantages of physostigmine and tacrine. Through a random
      screening, we incidentally found an N-benzylpiperazine derivative which showed
      positive cholinergic behavior in rats. We replaced the N-benzylpiperazine moiety
      with N-benzylpiperidine moiety and found a dramatic increase in anti-AChE
      activity. Even after the replacement of an amide group with a ketone group the
      activity was held. Furthermore, the cyclic-amide derivative showed enhanced
      inhibitory activity. On the basis of these results, an indanone derivative was
      designed. Among these indanone derivatives, donepazil hydrochloride (E2020),
      brand name ARICEPT was found to be the most balanced compound. The clinical
      studies of donepezil hydrochloride demonstrated statistically significant effects
      on ADAS-cog (Alzheimer's Disease Assessment Scale cognitive sub.) and CIBIC Plus
      (Clinician's Interview-Based Impression of Change plus).

PMID- 10067429
TI  - [Development of new asymmetric reactions utilizing carbanions].
AB  - New methods for asymmetric reactions developed by the author's group are
      outlined. They include asymmetric nitroolefination through an addition
      elimination process, asymmetric synthesis utilizing 2,2'-disubstituted and 8,8'
      disubstituted binaphthyl derivatives, and enantioselective alpha-alkylation of
      carbonyl compounds under conditions with absolutely no external chiral
      environmental factors.

PMID- 10067430
TI  - [Development of new reactions utilizing feature of sulfur atom and the
      applications].
AB  - Several novel reactions utilizing the latent feature of sulfur atoms have been
      developed. We found that chiral p-toluenesulfinyl groups on olefines control the
      stereochemistry in highly diastereoselective manners as show in the following
      three types of reactions: 1) intramolecular Michael addition reactions, 2)
      Pummerer-type reactions, and 3) cyclopropanation reactions. These chiral
      auxiliary groups are also very efficient for the asymmetric desymmetrization of
      sigma-symmetric diols via diastereoselective acetal fission. In addition, it was
      revealed that an aryl sulfide group on the cyclopropyl ring triggers single
      electron transfer reactions via cation radical species, resulting in the
      following reactions: 1) tandem oxidative ring cleavage-cyclization reactions and
      2) intramolecular [3 + 2] cycloaddition reactions. These reactions have been
      applied to the syntheses of natural products.

PMID- 10067431
TI  - [Effect of temperature on drug release and drug absorption in mixed type
      diclofenac sodium suppositories].
AB  - New types of diclofenac sodium suppositories known to control a drug release
      function for hospital preparations were developed based on a concept of the drug
      delivery system. Hard fat (Witepsol) used as a base of the suppository consists
      of a mixture of triglycerides, diglycerides and monoglycerides, and each Witepsol
      is characterized by its physicochemical properties. Authors disclosed that the
      amount of drug release measured in the commercially available diclofenac sodium
      suppositories decreased at a low temperature (36 degrees C). Mixed types of
      diclofenac sodium suppositories consisting of Witepsol W35 and Witepsol E85 as a
      base were also prepared and their drug release functions investigated in vitro
      and in vivo. The in vitro drug release properties changed with the mixing ratios
      of the two bases and with the temperature of the fluid tested. The amount of
      released diclofenac sodium increased with increases of both the ratio of Witepsol
      W35 in the suppository and the temperature of the test fluid. Moreover, several
      processes causing these phenomena were evidenced by the image analysis. The in
      vivo absorption of diclofenac sodium was found to be also influenced by these
      factors. Consequently, it is predicted that such factors as the ratio of Witepsol
      W35 in the suppository and the temperature will influence the drug absorption and
      the pharmacological effect of diclofenac sodium suppositories.

PMID- 10067432
TI  - [Study on the "signal" constituents for the evaluation of animal crude drugs. VI.
      The identification method of cervi parvum cornu in medicines using DNA analysis].
AB  - Cervi Parvum Cornu has been widely used as an agent in commercially available
      tonic medicines. The establishment of the method for the identification of each
      agent, especially crude drugs in formulations, is very important from the
      viewpoint of the quality control of drugs. In this paper, we reported the
      examination on the extraction method of DNA from the formulations, and also on
      the PCR method using four sets of primers, amplifying the DNA fragments of the
      regions of 12S rRNA and/or cytochrome b genes. The same size of DNA fragments as
      in the Cervi Parvum Cornu reference sample were found in all PCR products
      obtained from four commercial tonic medicines investigated. Therefore, it was
      confirmed that Cervi Parvum Cornu was contained in all the tonic medicines used.
      The PCR method was found to be a useful method for the identification of Cervi
      Parvum Cornu in tonic medicines and the DNA fragments amplified by the PCR method
      was clarified to be also helpful materials as index constituents for Cervi Parvum
      Cornu.

PMID- 10067433
TI  - Call to action in the 21st century. Creating a strategic plan for recruitment and
      retention of acute care staff.

PMID- 10067434
TI  - Getting results with integrity.

PMID- 10067435
TI  - SDM95: increase nursing ratios without adding cost through economic sizing and
      staffing to the 95th percentile.

PMID- 10067436
TI  - Transformation: caregivers can convert personal limitations into powerful healing
      capabilities.

PMID- 10067437
TI  - Ten steps to a strategic, service-driven focus.

PMID- 10067438
TI  - Nurse executives as champions of caring.

PMID- 10067439
TI  - Gaining a competitive advantage.

PMID- 10067440
TI  - Information: do we have too much of it?

PMID- 10067441
TI  - Crossing the border in health care. Learning the language and culture of Mexico.

PMID- 10067442
TI  - Why some teams succeed and others flop. And what you can do about it.

PMID- 10067443
TI  - How to hire hard so you can manage easy.

PMID- 10067444
TI  - Learn how to cough up that hairball!

PMID- 10067446
TI  - Keeping your eye on the ball: an open letter to nurse executives.

PMID- 10067445
TI  - Mastering the language of leadership.

PMID- 10067447
TI  - Multidisciplinary intervention programs and tools for integrating professional
      practice.

PMID- 10067448
TI  - What if Herb Kelleher, CEO of Southwest Airlines managed a hospital?

PMID- 10067449
TI  - Care management in a primary care depression team. Pilot project yields changes
      in treatment.

PMID- 10067450
TI  - Do we still value the magnet nursing service recognition program? Documenting
      excellence in quality service.

PMID- 10067451
TI  - Join the healthcare renaissance....

PMID- 10067452
TI  - Delegation: relief is just a swallow away.

PMID- 10067453
TI  - Minimal investments, maximum gain.

PMID- 10067454
TI  - HealthCare DIVERSOPHY--a cultural competence training tool for nurse executives.

PMID- 10067455
TI  - The patient care delivery mode at Mercy Medical Center: a licensed caregiver
      model.

PMID- 10067456
TI  - How have we engaged in our work? Integrating the internal and external.

PMID- 10067457
TI  - A competency model approach to redesigning the manager's role.

PMID- 10067458
TI  - Informatics & process improvement in real life. The clinical design unit.

PMID- 10067459
TI  - The Tapestry model: an innovative strategy for futuristic strategic planning.

PMID- 10067460
TI  - Coaching: a buzzword or a breakthrough management practice?

PMID- 10067461
TI  - Restructuring for partnership.

PMID- 10067462
TI  - Strengthening project management. Not just nice but necessary.

PMID- 10067463
TI  - A competency model approach to redesigning the manager's role.

PMID- 10067464
TI  - A new definition of empowerment.

PMID- 10067465
TI  - Where will you be in the new millennium?

PMID- 10067466
TI  - Planning, coaching, education: a big payoff.

PMID- 10067467
TI  - Maternal deaths.

PMID- 10067468
TI  - What would you have done?. Interview by Ina May Gaskin.

PMID- 10067469
TI  - Sovereignty in birth reclaimed.

PMID- 10067470
TI  - Ritual in the hospital: giving birth the American way.

PMID- 10067471
TI  - Childbirth and authoritative knowledge. Interview by Jane Bernstein.

PMID- 10067472
TI  - Physicians for midwives. Who we are.

PMID- 10067473
TI  - If you don't change directions, you're likely to end up where you're headed.
      Interview by Jane Bernstein.

PMID- 10067474
TI  - Birth stories. An ecstatic birth.

PMID- 10067475
TI  - A call for child advocacy.

PMID- 10067476
TI  - Coercion theory: application to the inpatient treatment of conduct-disordered
      children.
AB  - TOPIC: Conduct disorders in children are a phenomenon of concern in child and
      adolescent psychiatric nursing. PURPOSE: To review the major principles of
      coercion theory, provide an analysis of the relevant research, and discuss
      implications for inpatient nursing care. SOURCES: Published literature from the
      fields of medicine, nursing, psychology, sociology, and clinical experience.
      CONCLUSIONS: The principles of coercion theory are conceptually relevant in
      developing intervention strategies to treat conduct disorders and to interrupt
      escalation of aggressive behavior patterns in inpatient settings.

PMID- 10067477
TI  - Assessment of hospital-related stress in children and adolescents admitted to a
      psychiatric inpatient unit.
AB  - PROBLEM: The assessment of hospital-related stressors experienced by child and
      adolescent patients on a psychiatric inpatient unit. SUBJECTS: Child and
      adolescent inpatients (N = 40) admitted to an acute, short-term psychiatric unit.
      METHODS: A newly developed stressor survey was administered to subjects to
      identify the most problematic stressors. Correlation analyses were used to assess
      associations between hospital-related stress and adjustment variables. FINDINGS:
      Broad domains and specific items of the most problematic hospital-related
      stressors were revealed. Also, higher levels of hospital-related stress were
      consistently associated with poorer hospital-based adjustment. CONCLUSIONS:
      Implications for treatment include identifying hospital-related stressors for
      individual patients and providing interventions to enhance coping.

PMID- 10067479
TI  - Kaleidoscope of excellence. Interview by Linda M. Finke.

PMID- 10067478
TI  - Eating disorders and adolescents: an overview of a maladaptive behavior.
AB  - TOPIC: Eating disorders among the adolescent population are a serious health
      problem. The author provides an overview of anorexia nervosa and bulimia nervosa.
      PURPOSE: To present information on eating disorders that includes DSM-IV criteria
      and typical profiles of the client. Current hypotheses about the etiology of
      eating disorders, medical complications, treatment approaches, morbidity and
      mortality data research, and outcome research of treatment are reviewed.
      Research, treatment, and educational considerations for nursing care are
      discussed. SOURCES: Published literature, clinical experience. CONCLUSIONS:
      Advanced practice nurses are particularly suited for working with adolescents
      because of their holistic approach to client care. Inconsistencies and gaps in
      the knowledge base of eating disorders regarding incidence, etiology, treatment
      approaches, pharmacology, and outcome are areas for future nursing research.

PMID- 10067480
TI  - Update on mental health parity.

PMID- 10067481
TI  - Absconding: a literature review.
AB  - Incidents of absconding from inpatient care are high-risk events which have been
      linked to serious harm to self and others. This paper brings together for the
      first time findings from a disparate body of research literature spanning many
      years. Varied definitions of absconding and methods of calculating the rates of
      absconding make comparisons between studies difficult. Nevertheless, it is clear
      that absconders are more often young, male, from disadvantaged groups, and
      suffering from schizophrenia, compared to admissions generally. Roughly half of
      the abscondings take place while the patient is temporarily off the ward with
      permission, the remainder of absconding patients use an assortment of means to
      make their escape. A large variety of reasons for absconding have been elicited
      from patients or advanced as possibilities by researchers. Only six evaluative
      studies of interventions impacting upon absconding have been reported in the
      literature, but no firm conclusions can be drawn from them.

PMID- 10067482
TI  - Developments in mental health nursing: a critical voice.
AB  - This paper examines stances that are being adopted in relation to the current and
      future direction of mental health nursing practice. The argument is made that
      mental health nursing is being pushed into a direction that is essentially
      positivistic and narrow in its focus, stating that the current hegemony of
      thinking which dictates that our primary focus of concern should be with
      individuals suffering from severe or recurring mental illness, allied with the
      drive towards 'evidence based practice' is symptomatic of wider issues that
      should be of concern to all parties interested in the issue of mental health
      care. The authors examine the context and rationale for these developments from
      socio-political, philosophical and ethical viewpoints, highlighting that their
      logical outcome is the exclusion of individuals from the right to health care and
      question the motives underpinning what could be considered a fundamental shift in
      the provision of mental health services. The argument is then advanced that
      caution should be adopted by mental health nursing services before abandoning
      what Gournay (1994) described as 'redundant ideologies' and that a broader view
      of mental health nursing action should be accommodated. The validity of trying to
      account for mental nursing action in quantifiable and biomechanistic terms is
      questioned and an alternative paradigm of accounting for such action is
      suggested.

PMID- 10067483
TI  - Intensive care psychiatric nursing--psychoanalytic perspectives.
AB  - Based on unobtrusive observations, a parallel is drawn between general and
      psychiatric intensive care nursing. The correlation between bedside skills and
      the incidence of physical contact between nurse and patient in each setting is
      considered. The phenomenon of physical attacks by patients on carers and the
      process of restraint in the psychiatric intensive care unit (ICU) is then
      examined. It is suggested that attack by and subsequent restraint of a disturbed
      patient may be considered in terms of an unconscious re-enactment of an early
      skin-on-skin object relation. It is argued that the physical holding of a
      psychotic patient is functional in re-establishing their bodily ego. Some
      thoughts are offered on how the intensive care of psychotic patients might be
      carried forward in the future.

PMID- 10067484
TI  - Provision of out-of-hours support to a forensic population: strategies and
      research potential.
AB  - Community Mental Health Nurses (CMHNs) working within regional forensic services
      are increasingly expected to provide out-of-hours cover for community forensic
      patients. This is often in the absence of appropriate resources or indeed
      informed knowledge as to what are appropriate resources. In areas such as
      forensic services it would be assumed that out-of-hours cover is essential. Yet
      most forensic services find it difficult to provide this cover, because of the
      low number of CMHNs and the regional nature of the service. One option which has
      not been explored is the use of telephone support in conjunction with individual
      contingency plans for each patient. This paper explores this area and makes
      suggestions for researching outcomes for this service change.

PMID- 10067485
TI  - The effects of multisensory environments on older people with dementia.
AB  - This paper reports on the findings of an initial evaluation of the effects of
      exposing older people with dementia to a multisensory environment. Data collected
      about 29 patients demonstrated that this was generally a positive experience in
      terms of response to equipment and effect on behaviour. This was not the case for
      all patients, tactile equipment generating the most negative responses when it
      occurred. Several facets of behaviour, as judged by staff accompanying patients
      in the room, demonstrated desirable change over the session. Issues relating to
      refinement of the research methodology are discussed and the potential for such
      environments as tools for promoting communication is highlighted.

PMID- 10067486
TI  - Manufacturing a human drama from a psychiatric crisis: crisis intervention,
      family therapy and the work of R. D. Scott.
AB  - There has been a recent resurgence of interest in crisis intervention within
      psychiatry. The idea of crisis services is not, of course, a new thing, and there
      is a great deal to be learnt from returning to the innovative writings of those
      practitioners who developed similar services in the 1960s and 1970s. This article
      discusses the work of the psychiatrist and family therapist R. D. Scott, who
      developed a 24-hour family-orientated crisis intervention service in London
      during this era. Although under-utilized, the writings of Scott and his
      colleagues in this area continue to be of crucial relevance to mental health
      nurses and other psychiatric professionals.

PMID- 10067487
TI  - Evaluating learning opportunities offered to mental health nursing students.
AB  - This article is based upon a thesis submitted in partial fulfilment of the
      requirements of Anglia Polytechnic University for the degree of Master of
      Philosophy. The study, completed in 1997, sought to identify factors making a
      positive contribution to learning within mental health care settings, and, having
      done this, to develop a means of auditing. Phase One drew on published work;
      however, it was necessary to determine the contextual validity of factors shown
      by colleagues to be conductive to learning, since the focus of this earlier work
      was, in the main, within general adult nursing. Information on the relevance of
      these factors was obtained from a sample (n = 146) of mental health nursing
      students, qualified staff, and teachers who responded to a self-completion postal
      survey, using a questionnaire as the research instrument. Phase Two drew upon the
      work completed in Phase One. A Likert-type scale audit instrument was developed
      and administered to a sample (n = 51) of mental health nursing students. In order
      to test the reliability of this instrument, students'verbal ratings of the
      quality of their learning experience were compared to numerical ratings provided
      by the audit instrument resultant from this study. Findings suggest that the
      instrument provides an effective, efficient means of evaluating learning
      environments from an individual student's perspective, and as a cumulative
      profile of student, practice setting and supervisors operating within it. This
      enables educationalists to identify standards which may be incorporated into
      future education/service provider contracting arrangements.

PMID- 10067488
TI  - Objective measurement of mood change induced by contemporary music.
AB  - A myriad of previous studies from a variety of disciplines has shown several
      effects of music on mind and body. This study investigated the relationship
      between different categories of contemporary music (n = 6) and the mood states of
      a group of students (n = 12), using the Profile of Mood States (POMS), to measure
      mood before and after exposure to these different pieces of music. When analysed
      together, all six pieces of music produced an overall change in mood (P = 0.008)
      as measured by 2-way repeated measures analysis of variance (ANOVA). When each
      category was examined individually, four categories of music produced highly
      significant changes in mood: the tense category (score -4.0 +/- 1.8 POMS Units; P
      < 0.001); depressed category (+0.5 +/- 0.2; P < 0.001); angry category (+0.9 +/-
      1.6; P < 0.03); and the all moods category (1.6 +/- 0.3; P < 0.04). One piece of
      dance music produced changes in all mood categories, giving the largest positive
      mean mood change. By contrast, the popular/independent music, associated with the
      tense category, produced the largest negative mean mood change. The five POMS
      mood states were analysed separately for each piece of music. These findings are
      consistent with previous work. In addition, the finding of the effects of
      specific music categories on mood may have important implications for therapy in
      mental health and mental health nursing.

PMID- 10067489
TI  - The effects of spiritual practices on recovery from substance abuse.
AB  - Twelve-step programs have stressed the importance of spiritual practices for over
      four decades. The spiritual principles embodied in the twelve-step programs may
      be key in their success of recovering addicts/alcoholics with an overall recovery
      rate of 34%. A literature search revealed little available data on spiritual
      principles and practices and their effects on long-term recovery from substance
      abuse. This study compared two groups of recovering addicts, those with one year
      of recovery and those with less than one year and a history of relapse. Spiritual
      practices were measured using a five-point Likert scale questionnaire. The
      results of the study indicated a relationship between spiritual practices and
      long-term recovery from substance abuse.

PMID- 10067490
TI  - Stress and the quality of life in the parents of young people with intellectual
      disabilities.
AB  - This paper reports the results of a study into stress and quality of life in the
      parents of young people with an intellectual disability. Research in this area
      often finds that parents suffer stress as a result of having a son or daughter
      with an intellectual disability. According to Glidden (1993), this has led to the
      mistaken perception amongst researchers and professionals in the field that these
      parents are maladjusted. Glidden's work with parents adopting children with an
      intellectual disability suggest the parenting may be a satisfying experience and
      suggests a research focus based on outcomes. In this study the participants,
      including 102 parents of young people with (44) and without (58) an intellectual
      disability, were mailed a stress questionnaire and quality of life questionnaire.
      The results of the analysis of these data demonstrate that the families with a
      member with a disability report significantly greater stress, they also
      demonstrated that as stress increases the quality of life decreases. Governments
      need to address this problem if current policies of integrating people with
      intellectual disabilities into the community are to be successful. This paper
      also discusses the reasons natural parents of people with disabilities are
      dissatisfied while adopting parents are not and suggests further research into
      this important topic.

PMID- 10067491
TI  - Using technology to enhance psychological well-being.

PMID- 10067492
TI  - The Robinson Unit: a step-down unit for people recovering from acute mental
      illness.

PMID- 10067493
TI  - Acute admission psychiatric nursing.

PMID- 10067538
TI  - Getting involved in curriculum planning.

PMID- 10067539
TI  - Understanding statistics. 1. Data and data summaries.

PMID- 10067540
TI  - Prep and profiles. A framework in the making.

PMID- 10067541
TI  - Learning in clinical practice. 5. Evaluating student performance.

PMID- 10067542
TI  - Evaluating healthcare systems.

PMID- 10067543
TI  - Mental health therapies.

PMID- 10067544
TI  - Powerful presentations: prepare to be heard.

PMID- 10067545
TI  - The disease management approach to cost containment.
AB  - Disease management has been around a long time, certainly since Pasteur. Its
      initial focus was to eliminate or contain epidemics. In the 20th century,
      American public health scientists and officials have used disease management to
      address a high-risk, often poor population. Currently, the population-based
      principles of disease management, including disease prevention activities, are
      being applied to noninfectious diseases. Two examples of public health disease
      prevention strategies are vaccinations and chlorination of water. Hospitals are
      now providing post-hospital disease management programs for selected chronic
      conditions that account for a high volume of repeat admissions or emergency
      department visits, such as chronic heart failure, asthma, and cancer. In other
      words, hospitals are spending money on a program that, if done right, will reduce
      their inpatient revenues. They are doing so for various reasons (e.g., because
      they have established at-risk financial partnerships with their physicians, or
      possibly because other area hospitals are doing it, or possibly because they want
      to keep the ancillaries [x-rays, laboratory, pharmacy, ambulatory surgery, etc]).
      Regardless of the reasons, hospital case managers will be charged with referring
      qualified patients to both hospital-based and provider-based disease management
      programs.

PMID- 10067546
TI  - The long and winding road: merging two case management programs in a developing
      healthcare network.

PMID- 10067547
TI  - Outcomes for patients with congestive heart failure in a nursing case management
      model.
AB  - Congestive heart failure is a leading cause of hospital admissions, costing an
      estimated $7 billion in 1990. Hospital-based nursing case management has been
      used to reduce costs of care while maintaining quality of care. This study
      describes the outcomes for 50 patients with congestive heart failure in a
      hospital-based nursing care management model, providing general outcomes,
      physiologic status, physical functioning, health knowledge, and family caregiver
      status. The number of medications was the only predictor of length of stay using
      regression analysis.

PMID- 10067548
TI  - Navigating critical pathway selection.

PMID- 10067549
TI  - Advanced nurse practice. A model for collaboration.
AB  - The authors present an argument for separate advanced practice nursing roles. A
      model is presented for collaborative practice between two advanced practice
      nursing roles--a nurse practitioner and a clinical nurse specialist/case manager.
      The model was developed from the clinical practice of the authors' work in a
      community health center. A clinical example is provided that explicates the
      distinct and separate roles of each provider and demonstrates their collaboration
      to provide excellent, cost-effective healthcare.

PMID- 10067550
TI  - Determining case manager workload: are there secrets to success?

PMID- 10067551
TI  - Automated clinical pathways in the patient record legal implications.
AB  - Nurses have long been taught the need for precise documentation of patient care.
      Yet, as demands on nurses' time increases, maintaining an accurate and
      informative patient record becomes more difficult. The use of an automated
      clinical pathway that contains both the plan of care and a record of the care,
      while increasing communication between the care providers, is a promising
      solution to the problem. In this article, the process of moving a clinical
      pathway from paper to a computerized format is discussed. Legal issues related to
      its status as a permanent part of the patient record are considered. The legal
      implications of the pathway as a standard of care are also examined. As clinical
      pathways and computers merge, effective automated plans of care that also can
      serve as a documentation tool will benefit both the caregiver and the patient,
      while decreasing the risk of liability.

PMID- 10067552
TI  - Health care education for dialogue and dialogic relationships.
AB  - This article will address the question: how can health care education best take
      seriously the task of educating for professional practice within a post
      traditional, liberal democratic society? In the setting of modernity, the altered
      personal and professional self has to be explored and constructed as part of a
      reflective process of connecting personal and professional change: in essence, to
      develop self-knowledge. A moral life, or 'working morality', that evolves out of
      a process of ongoing dialogue and conversation is required. What is advocated
      here is a more social model of health care education that acknowledges a social
      or communal dimension to knowledge and the centrality of relationships for the
      full development of the individual personally and professionally, fosters our
      capacity to identify who we are both personally and professionally, connects
      reason and dialogue, and educates for dialogue and dialogic relationships.

PMID- 10067553
TI  - The authenticity and ethics of phenomenological research: how to overcome the
      researcher's own views.
AB  - This article is based on the assumption that the researcher cannot detach from
      his or her own view in phenomenological research. The researcher is assumed to be
      able to understand the experiences of an individual only through the points of
      departure created by the researcher's own view. The goal of this article is to
      describe practical aspects and their theoretical grounds that are of crucial
      importance in overcoming a researcher's views in data gathering and analysis. Its
      purpose is to clarify the authenticity and ethical standards concerning the views
      of the researcher in phenomenological research.

PMID- 10067554
TI  - Living with dementia: communicating with an older person and her family.
AB  - This article is designed to explore and examine the key components of
      communication that emerged during the interactional analysis of a role play that
      took place in the classroom. The 'actors' were nurses who perceived the
      interaction to reflect an everyday encounter in a hospital ward. Permission to
      tape the interaction was sought and given by all persons involved. The principal
      'players' in the scenario were: the patient, a 70-year-old-woman who had been
      admitted with dementia, her son and daughter, and the nurse in charge of the
      ward. The fundamental dynamics of the use of power and restriction, truth
      telling, family stress, interpersonal conflict, ageism, sexism, empathy and
      humanism surfaced during the analysis. The findings show that therapeutic
      communication should be the foundation on which nursing should stand. The article
      continues with an exploration of the theoretical frameworks that guided the
      analysis of interaction and concludes by suggesting tentatively some meaningful
      implications for nursing practice. It plans to furnish provocative new insights
      into the sometimes covert communication dynamics occurring within the nurse
      patient relationship. Finally, it aims to generate discussion on this little
      charted realm of human social interaction.

PMID- 10067555
TI  - The person in abortion.
AB  - The issue of what constitutes a person is examined in relation to whether or not
      the fetus or newborn has qualities of personhood. The discussion also dwells on
      birth and viability as determining factors in decisions concerning terminations.
      Such decisions are stated to be constrained by both biological and social
      factors, particularly in the way in which the fetus can possess personhood only
      through the 'absorption' of such from its mother; both mother and fetus together
      are 'the person'. This article also considers whether, on Piagetian grounds, one
      can make personhood comparisons between infants and adults and suggests that such
      comparisons are a mistake. A social critique of Piagetian principles shifts the
      emphasis from individualism towards consideration of school, family and
      environmental factors. Equally, it is not feasible to view the fetus as an entity
      that is separate from its mother's perceptions of its social as well as its
      physical status. Finally, because termination decisions occur against 'real life'
      (and highly charged) backgrounds, we must reject any notion that such decisions
      are only an intellectual exercise. It is assumed that nurses would implicitly
      understand this and some attempt is made to state why this is so.

PMID- 10067556
TI  - Abortion: why bioethics can have no answer--a personal perspective.
AB  - Abortion is one of the great moral debates of the epoch. Is there a rational
      method by which the debate can be resolved? Can bioethics' promise of such a
      method be fulfilled? Surely, a strictly rational approach can establish solid
      grounds for our beliefs once and for all. We would then be justified in deeming
      as unreasonable anyone who does not accept the perfectly rational conclusions. I
      present two scenarios to show that there can be no such philosophically grounded
      method and therefore no such facts to which everyone must agree. This does not
      mean that it is in fact impossible for people to reach agreement. It simply means
      that there is no incontrovertibly rational means by which they must do so.

PMID- 10067557
TI  - Health needs of lone elderly Chinese men with heart disease during their
      hospitalization.
AB  - Hospitalization is a unique health-illness transition for most elderly people.
      Whether the patient's health-related needs are met or not often influence his or
      her appraisal of quality of life during hospitalization. This qualitative study
      explored the health needs of elderly Chinese male cardiac patients during their
      hospitalization. Eighteen subjects were recruited from a veterans' hospital in
      northern Taiwan. These men all lived alone before their hospital admission. Data
      were gathered using semistructured interviews and then analysed by content
      analysis. Ninety-four per cent of the subjects described up to three categories
      of needs: met needs (72%), unmet needs (78%), and expected needs (50%). Needs
      that participants believed were met were those for psychological support,
      spiritual support, tangible support and information. Unmet needs were those for
      participation in decision making, maintaining daily activities and resuming a
      preadmission lifestyle. The expected needs included those for learning self-care
      strategies to maintain their daily activities after discharge from the hospital.
      The factors that framed the participants' perceptions of different health needs
      were identified to be lack of family support and locus of control. Finally, a
      discussion of the context background of this phenomenon, as well as some
      suggestions for its implications, are provided from a culturally sensitive
      ethical aspect.

PMID- 10067558
TI  - Ethical considerations in qualitative research with vulnerable groups: exploring
      lesbians' and gay men's experiences of health care--a personal perspective.
AB  - It is rare to find honest accounts of the difficulties and dilemmas encountered
      when conducting sensitive research with vulnerable research populations. This
      account explores some of the ethical issues raised by a qualitative interview
      study with lesbians and gay men about their experiences of nursing care. There is
      tension between the moral duty to conduct research with vulnerable and
      stigmatized groups in order to improve care, and the inevitable lack of resources
      that go with such a venture. This increases the risk of harm during the process
      of research. The risk of harm to both the researchers and the researched is
      explored and the need for a support structure for both groups is raised. There is
      a pressing need to develop further understanding about the ways in which the
      dissemination of research can potentially harm already vulnerable research
      populations.

PMID- 10067560
TI  - Trusts struggling to deliver quality care.

PMID- 10067559
TI  - Child care: why nurses are getting a raw deal.

PMID- 10067561
TI  - From here to maternity.

PMID- 10067562
TI  - Testing times.

PMID- 10067563
TI  - Cash for nurses' pay rises spent on Romanian asylum-seekers?

PMID- 10067564
TI  - Arena with friends like these....

PMID- 10067565
TI  - Are you sitting comfortably?

PMID- 10067566
TI  - Laugh? I nearly cried.

PMID- 10067567
TI  - Back to front.

PMID- 10067568
TI  - Pilonidal sinus: the bottom line.

PMID- 10067569
TI  - Tales of the expected.

PMID- 10067570
TI  - Let's move on up.

PMID- 10067571
TI  - NT/3M National Nursing Awards. Trained for life.

PMID- 10067572
TI  - Face to face. Interview by Eileen Fursland.

PMID- 10067573
TI  - Measuring the sleep patterns of older people.
AB  - This paper examines a pilot study analysing sleep in nursing care settings. Sleep
      aids recovery, and affects the quality of life of older people in care settings.
      Issues are raised about the sleep measurement for research, and feasibility and
      rigour; new instruments are introduced; the value of self-reported and observed
      sleep data is discussed and recommendations are made.

PMID- 10067574
TI  - Dealing with the dilemmas of confidentiality.
AB  - The duty of nurses to maintain patient confidentiality can be influenced by a
      number of factors. This article discusses the circumstances under which nurses
      may decide, or be constrained, to share information about a patient. It argues
      for greater clarity in the guidance given to nurses regarding confidentiality.

PMID- 10067575
TI  - Working with confidentiality.

PMID- 10067576
TI  - How to achieve effective diabetes management.

PMID- 10067577
TI  - Improving outcomes through preoperative teaching.

PMID- 10067578
TI  - Continence problems: how to tackle reticence of patients.

PMID- 10067579
TI  - Could do better.

PMID- 10067580
TI  - Back to the future.

PMID- 10067581
TI  - Attitude problem.

PMID- 10067582
TI  - Why are we waiting?

PMID- 10067583
TI  - Poor ward preparation.

PMID- 10067584
TI  - Enter the dragon.

PMID- 10067585
TI  - Project 2000 is to blame for nurse shortages.

PMID- 10067586
TI  - The untouchables.

PMID- 10067587
TI  - Nurses get the credit as waiting list measures begin to bite.

PMID- 10067588
TI  - A double blow. Interview by Rebecca Coombes.

PMID- 10067590
TI  - Professionalism.

PMID- 10067589
TI  - Oil on troubled waters.

PMID- 10067591
TI  - What you think of doctors.

PMID- 10067592
TI  - Spectre at the feast.
AB  - The government's vision, reflected in both the white paper The New NHS: Modern,
      Dependable (Department of Health, 1997) and circulars since is of GPs and
      community nurses working together in primary care groups to shape services for
      patients. But the short history of PCGs has seen nurses having to fight for
      representation. There is also cynicism about the outcome, nurses having a maximum
      of two members, GPs seven. Is an equal working relationship really possible? This
      snapshot survey examines professionalism and collaborative working in primary
      care. The results suggest that without changes in structure, understanding and
      attitudes by both doctors and nurses a relationship of equality is not likely.

PMID- 10067593
TI  - A hole lot more.

PMID- 10067594
TI  - Primary care. Pilot light.

PMID- 10067595
TI  - NT/3M National Nursing Awards. Keeping up to date on current affairs.

PMID- 10067596
TI  - In our parents' shadow. Prader-Willi syndrome.

PMID- 10067597
TI  - Open to attack.

PMID- 10067598
TI  - Collecting a mid-stream specimen of urine.

PMID- 10067599
TI  - Flu is wreaking havoc.

PMID- 10067600
TI  - Support for the carers of people with schizophrenia.

PMID- 10067601
TI  - Assessment and management of erectile dysfunction.

PMID- 10067602
TI  - Living with a cardioverter defibrillator in the community.
AB  - Internal cardioverter defibrillators are increasingly used for the treatment of
      life threatening arrhythmias. Patients and their families have described many
      emotional and psychological consequences of living with these devices. The impact
      on family members of providing high levels of support can lead to stress-related
      problems, yet their needs are often underestimated or overlooked.

PMID- 10067603
TI  - Cold comfort.

PMID- 10067604
TI  - Isolated instance.

PMID- 10067605
TI  - Taking the strain.

PMID- 10067606
TI  - Nurse attacked: suit against patient's psychiatrist.

PMID- 10067607
TI  - Failure to adequately "monitor": $1.5 million dollar verdict. Case on point:
      Adams v. Cooper Hospital. 684 A. 2d 506--NJ (1996).

PMID- 10067608
TI  - WI: HMO refuses to pay for treatment: breach of contract and bad faith alleged.

PMID- 10067609
TI  - TX: transport team drops patient: malpractice limitations not applicable.

PMID- 10067610
TI  - Neonatal nurse's reprehensible conduct results in revocation. Case on point:
      Mississippi Board of Nursing v. Hanson 703 So. 2d 239--MS (1997).

PMID- 10067611
TI  - Patient dies of heart attack: did nurses "drop the ball"?

PMID- 10067612
TI  - Did this nurse euthanize her patient? Case on point: Dobisky v. Rand, 670
      N.Y.S.2d--NY 606 (1998).

PMID- 10067613
TI  - MO: pt. sues nursing home-limitations issue: no "continuous treatment exception"
      applies.

PMID- 10067614
TI  - NC: failure to assert expert's review of case: court holds dismissal of case is
      mandatory.

PMID- 10067615
TI  - Nurse peer review records not totally privileged. Case on point: Adams v. St.
      Francis Regional Med. Ctr., 955 P.2d 1169-KS (1998).

PMID- 10067616
TI  - Did advocacy for patients' rights result in termination?

PMID- 10067617
TI  - What do you do when faced with an incompetent director of nursing? Case on point:
      Yearous v. Niobara County Memorial Hospital. 128 F. 3d 1351--(1997).

PMID- 10067618
TI  - NY: co-worker sues employer's nurse: compensation is exclusive remedy.

PMID- 10067619
TI  - MN: nurse fails to report sexual abuse: testimony under "dissassociative state".

PMID- 10067620
TI  - Nurse attacked by teen pt.: "discretionary" immunity issue. Case on point: Ludlow
      v. City of Clifton 702 A. 2d 506--NJ (1997).

PMID- 10067621
TI  - Hospital fails to diagnose CVA; EMTALA suit follows.

PMID- 10067622
TI  - Manning hospital hotlines can be risky for nurses. Case on point: Starkey v. St.
      Rita's Med. Ctr. 690 N.E. 2d 57--OH (1997).

PMID- 10067623
TI  - LA: failure to pay child support as ordered: license to practice nursing
      suspended.

PMID- 10067624
TI  - NY: aide threatens life of supervisor, etc.: dismissal for "misconduct" affirmed.

PMID- 10067625
TI  - Board suspends license: court reverses on "jurisdiction" issue. Case on point:
      Regester v. Indiana State Bd. of Nursing, 689 N.E.2d 477--IN (1997).

PMID- 10067626
TI  - Fund pays ten million: pursues nurse and her insurer.

PMID- 10067627
TI  - Doctor orders nurses not to "code" patient. Case on Point: Wendland v. Sparks,
      574 N.W. 2d 327--IA(1998).

PMID- 10067628
TI  - NY: patient falls from bed--$150,000 verdict: nurse expert precluded from
      testifying.

PMID- 10067629
TI  - DC: CNA charged with abuse of patient: name placed on nurse aide registry list.

PMID- 10067630
TI  - Can state retroactively limit times NCLEX taken? Case on Point: Yap v. Zollar 691
      N.E. 2d 18--IL(1997).

PMID- 10067631
TI  - Wrongful refusal to authorize treatment: do we care?

PMID- 10067632
TI  - Court holds hospital has duty to employees' spouses. Case on point: Bolieu v.
      Sisters of Providence in Wash., 953 P. 2d 327--Alaska (1998).

PMID- 10067633
TI  - NY: emergency intubation--no consent issue: extubation results in suit v. R.N. &
      M.D.

PMID- 10067634
TI  - CO: suit for violation of EMTALA, etc.: arbitraton act no bar to suit against
      nurse.

PMID- 10067635
TI  - Patient's legs broken during transfer: $1.25 million verdict. Case on point:
      rehabilitation facility at Austin v. Cooper 962 S.W. 2d 151--TX (1998).

PMID- 10067636
TI  - How will you use your influence?

PMID- 10067637
TI  - An analysis of patients' psychosocial adjustment and values before and after
      coronary artery surgery.
AB  - This study describes the impact of coronary artery bypass graft (CABG) surgery on
      patients' personal values. The relationship between the difference in value ranks
      and psychosocial adjustment to CABG surgery was also investigated. A one-group
      pretest-posttest design was employed to identify the differences between pre- and
      postsurgery value ranks. A consecutive sample of 67 participants ranked two sets
      of 18 values using the Rokeach Value Survey 1 day before and 6 months after
      surgery. At 6 months after surgery, psychosocial adjustment was also measured,
      using the Psychosocial Adjustment to Illness Scale (PAIS). A Pearson product
      moment correlation was calculated to test the hypothesis that a direct
      relationship exists between the difference in value ranks and positive
      psychosocial adjustment to CABG surgery. Fifty-six participants completed the 6
      month follow-up survey. The median value ranks for the three most and least
      important values of each set were essentially the same for the ranks obtained
      before and after surgery. The PAIS results obtained 6 months after surgery
      indicated that all but 4 of the 56 participants had a positive psychosocial
      adjustment to surgery. There was no significant relationship between PAIS and
      value difference scores.

PMID- 10067638
TI  - Relationships between adherence, sense of coherence, and knowledge in cardiac
      rehabilitation.
AB  - Seventy-nine subjects took part in a cross-sectional study to investigate
      knowledge of and adherence to lifestyle recommendations 2 years after cardiac
      rehabilitation. The relationship of adherence, Antonovsky's sense of coherence
      (SOC) concept, and knowledge also were explored. Data were collected via a mailed
      questionnaire. The majority of the subjects showed a high degree of program
      related knowledge and a significant increase in desired behaviors. A modest
      correlation was found between knowledge and SOC, whereas, contrary to
      expectations, there was no significant association between SOC and adherence. The
      results question the concept of adherence to medical regimens as a measure of
      successful coping.

PMID- 10067639
TI  - Cardiac rehabilitation referral and attendance: not one and the same.
AB  - Despite empirical evidence that cardiac rehabilitation programs can play a
      significant role in enhancing recovery following a primary cardiac event and in
      enacting secondary prevention measures, attendance rates remain remarkably low.
      Referral and attendance at cardiac rehabilitation programs are not one and the
      same. Recognizing this, issues related to the referral of eligible patients to
      cardiac rehabilitation and factors that affect patients' decisions regarding
      attendance must be identified and addressed. This article presents an overview of
      the potential benefits of cardiac rehabilitation programs, describes salient
      issues related to referral and attendance, and identifies directions for future
      research.

PMID- 10067640
TI  - The relationship between caregiver burden and TBI survivors' cognition and
      functional ability after discharge.
AB  - This exploratory correlational clinical study examines the relationship between
      reported caregiver burden (as measured by the Burden Interview) and cognition and
      functional ability (as measured by the Functional Independence Measure
      instrument) of people who had experienced traumatic brain injury (TBI). The
      purpose of the research was to explore the impact of cognition and functional
      ability in adults with TBI on perceived caregiver burden. Forty-two subjects with
      TBI and their caregivers were studied during the follow-up clinic appointment 3
      months after discharge from a 31-bed inpatient rehabilitation unit. Demographic
      data and relationships to previous studies were explored. Pearson correlation
      matrixes and a simple single regression model were used to examine the
      relationships. Functional ability and cognition both negatively affected reported
      caregiver burden, although the relationship was not statistically significant.

PMID- 10067641
TI  - The relationship between caregiver burden and self-care deficits in former
      rehabilitation patients.
AB  - This study examined the relationship between caregiver burden and self-care
      deficit in former rehabilitation patients. We hypothesized that as self-care
      deficit increases, so does the level of caregiver burden. We employed Spearman
      correlational analysis and stepwise multiple regression analyses; the mean
      caregiver burden score was 25.9 (SD = 17.1), indicating mild to moderate burden.
      Caregiver burden was significantly correlated with social cognition deficit (r =
      0.438, p = .001), communication deficit (r = 0.430, p = .001), and self-care
      deficit (r = .426, p = .002). Significant predictors of burden were social
      cognition deficit (beta = .408, p = .0018), self-care deficit (beta = .322, p =
      .0100), and caregiver age (beta = .369, p = .0312).

PMID- 10067642
TI  - The Balanced Budget Act of 1997: how the prospective payment system affects
      providers of rehabilitation services.

PMID- 10067643
TI  - Successful ventilator weaning: a collaborative effort.

PMID- 10067644
TI  - Miracles do happen.

PMID- 10067645
TI  - Quality in child healthcare. The views of mothers and public health nurses.
AB  - In child health promotion (CHP) programmes it is the public health nurse who is
      responsible for most of the work. However, the perspectives of the family and the
      staff must be identified in order to get a comprehensive picture of significant
      quality factors in child healthcare. One aim of this study was to assess the
      views of mothers and public health nurses concerning a CHP programme and the
      first home visit to parents of newborn children. Other aims were to compare
      mothers' and nurses' views of CHP programmes in relation to age, experience,
      structure of organization and urbanization, and mothers' views in relation to
      social position, health of the children, primi- or multipara, country of birth
      and urbanization. Two national postal questionnaires, one sent to the mothers
      (850), the other to public health nurses (291), yielded data for analysis. Both
      mothers' and public health nurses' views of what constitutes good child
      healthcare were found to concur with the official goals of child health
      promotion. Important quality indicators were said to be: kind treatment,
      competence, time, support, an all-round view, the individual perspective, and
      home visits to primipara parents.

PMID- 10067646
TI  - Parenthood as talked about in Swedish ante- and postnatal midwifery
      consultations. A qualitative study of 58 video-recorded consultations.
AB  - In order to explore the manner in which parenthood was discussed in midwifery
      consultations, 58 video-recorded consultations were analysed. A content analysis
      revealed a variety of topics concerning conversation on parenthood--topics of an
      intimate nature and discussions from a societal perspective. Parenthood was not
      of primary importance in visits, which were mostly directed by the midwives. A
      phenomenological hermeneutic analysis of the meaning of being a mother revealed a
      complex and difficult situation of being both needed and dependent. The meaning
      of being a father revealed a struggle between distancing from and closeness to
      the child. The mate relationship was indicated as important and under strain. The
      metaphor of the 'spiders web', where the mother is the spider with the child
      mostly on her back, the father entering the web on her terms, summarizes the
      understanding. The results from this study could provide a basis for reflection
      on the status of the topic of parenthood, on the meaning of being a mother and a
      father disclosed in the consultations, and ultimately on the organization of ante
      and postnatal midwifery care.

PMID- 10067647
TI  - The Norwegian version of the Quality of Life Scale (QOLS-N). A validation and
      reliability study in patients suffering from psoriasis.
AB  - The aim of this study was to adapt, validate, and test for reliability the
      Quality of Life Scale in Norwegian (QOLS-N) for patients suffering from
      psoriasis. Two hundred and eighty-two patients with psoriasis were included in
      the study. Self-reported health was measured using the SF-36. Disease severity
      was also measured in 95 patients using the Psoriasis Area and Severity Index
      (PASI). The reliability of the QOLS-N was computed using the internal consistency
      reliability (Cronbach's alpha) and the test-retest reliability test. Face and
      content validity and construct discriminant ability of the QOLS-N were assessed.
      The results indicated that the QOLS-N has highly satisfactory rates of test
      retest reliability (r = 0.83) and internal consistency reliability (alpha 0.86).
      As expected, the QOLS-N had a lower correlation with physical health (r = 0.24, p
      < 0.000) and self-reported symptoms (r = -0.20, p < 0.001), and a higher
      correlation with mental health (r = 0.52, p < 0.000). The correlation with
      disease severity was not significant (-0.06). The results reported in the present
      paper are in accordance with those derived in other validation studies. The QOLS
      N seems to be a reliable and valid measure of global quality of life in patients
      suffering from psoriasis.

PMID- 10067648
TI  - Coping strategies and quality of life among patients on hemodialysis and
      continuous ambulatory peritoneal dialysis.
AB  - A consecutive series of hemodialysis (HD) patients (n = 30) was included in a
      descriptive-comparative design. The aim was to study coping strategies and
      quality of life compared to a group of patients on continuous ambulatory
      peritoneal dialysis (CAPD). Coping was measured on the Jalowiec Coping Scale.
      Quality of life was measured by the Swedish Health-Related Quality of Life Survey
      (SWED-QUAL). An optimistic coping style was the most widely adopted by men and
      women in both groups, and this style was also considered to be the most effective
      in terms of dealing with stressful treatment aspects. The HD sample used more
      evasive coping strategies than the CAPD sample. Compared to a sample from the
      general population, HD patients had lower values on all SWED-QUAL subscales.
      Further, the CAPD women scored lower on general health than did the HD women.
      Significant gender differences were found in that men in both samples regarded
      themselves as better able to cope with physical aspects of the illness. Women in
      both samples scored lower on general health. It seems important to identify
      patients who use emotive, evasive and palliative coping techniques extensively,
      because they seem to be less effective at handling their illnesses.

PMID- 10067649
TI  - Meals in nursing homes. An ethical appraisal.
AB  - The ethical approach of artificial administration of food and fluids has been
      much enlivened in recent years. Nevertheless, the ethical implications of the day
      to-day event of serving meals in nursing homes remain to be clarified. This paper
      has a double aim. First, I present a philosophical-ethical clarification of
      mealtime care in nursing homes. Second, I suggest several ethical orientations
      related to the nutritional problem among nursing home residents. I argue that
      caregivers must not only have considerable knowledge and skill in nutritional
      matters; it is only by integrating as much as possible an attitude of caring with
      the competent performance of care activities that 'good mealtime care' can be
      achieved.

PMID- 10067650
TI  - Cancer patient and staff perceptions of caring and clinical care in free versus
      forced choice response formats.
AB  - Two questions were investigated: whether cancer patients (n = 32) and staff (n =
      30) have different cognitive representations of the concepts 'caring' (Swedish:
      'omvardnad') and 'clinical care' (Swedish: 'vard'), and whether results differ
      between forced vs. free choice response formats. Two Swedish versions of the CARE
      Q instrument were used: (i) a CARE-Q sorting (forced format) and (ii) a CARE
      Questionnaire (free format). Four groups of patients and 4 groups of staff
      completed (i) the forced format/caring, (ii) the forced format/clinical care,
      (iii) the free format/caring and (iv) the free format/clinical care versions,
      respectively. Participants were asked to rank the importance of 50 CARE-Q
      behaviours for the specific method/concept combination. Results demonstrated that
      neither patients nor staff, to any great extent, valued CARE-Q subscales
      differently when regarded as examples of 'caring' vs. 'clinical care'. Further,
      the free vs. forced choice format did not influence patient and staff perceptions
      of the importance of CARE-Q subscales, except that both groups gave higher values
      to all subscales in the free choice response format. The assumptions that
      different cognitive representations of the concepts or the response formats had
      affected previous CARE-Q results were not substantiated.

PMID- 10067651
TI  - Neonatal death and parents' grief. Experience, behaviour and attitudes of Swedish
      nurses.
AB  - The aim of the present study was to survey the experience, behaviour and
      attitudes of nurses in Swedish neonatal wards towards parents who refuse or are
      reluctant to see, touch or hold their dying or dead baby. A questionnaire was
      distributed to 173 nurses, of whom 144 responded. The questionnaire contained
      questions about the nurses' own experience of such situations, their behaviour,
      and their attitude towards influencing the parents. Seventy-four percent answered
      that they had experience of such situations, 59% that they often tried to
      persuade or in other ways influence the parents to change their mind, and 60%
      were of the opinion that the parents mourning-process is always facilitated when
      they touch or hold their dead baby. Most nurses (83%) were of the opinion that
      the conflict between beneficence and autonomy was difficult but not impossible to
      solve. A majority of the nurses were inclined to give priority to the principle
      of beneficence. But is this inclination ethically justified? A well-founded
      answer to this question requires more knowledge about the experiences of parents
      who have lived through such traumatic situations.

PMID- 10067652
TI  - A nutritional requirement: the need for research, education, and health claims.

PMID- 10067653
TI  - Mechanisms of chromium action: low-molecular-weight chromium-binding substance.
AB  - Chromium has long been known to be essential for proper lipid and carbohydrate
      metabolism in mammals, with chromium deficiency leading to symptoms associated
      with adult-onset diabetes and cardiovascular disease. Elucidating the structure,
      function, and mode of action of the biologically active form of chromium has
      proved enigmatic. However, a naturally-occurring oligopeptide, low-molecular
      weight chromium-binding substance (LMWCr), has been found in our laboratory to
      activate insulin receptor kinase activity up to 7-fold with a dissociation
      constant of 250 picomolar in the presence of 100 nanomolar insulin, and it has
      been partially characterized in terms of structural and spectroscopic properties.
      LMWCr may function in a manner similar to that of the calcium-binding signal
      protein calmodulin. In other words, LMWCr is maintained in its active apo
      oligopeptide form; in response to a chromium flux, LMWCr binds 4 chromic ions.
      The holoprotein is then capable of binding to insulin receptor (and perhaps other
      enzymes) activating the enzyme. Establishing a link between the nutrient
      chromium, LMWCr's activation of insulin receptor kinase activity, and adult-onset
      diabetes and related conditions could result in a new treatment for these
      conditions.

PMID- 10067654
TI  - High doses of multiple antioxidant vitamins: essential ingredients in improving
      the efficacy of standard cancer therapy.
AB  - Numerous articles and several reviews have been published on the role of
      antioxidants, and diet and lifestyle modifications in cancer prevention. However,
      the potential role of these factors in the management of human cancer have been
      largely ignored. Extensive in vitro studies and limited in vivo studies have
      revealed that individual antioxidants such as vitamin A (retinoids), vitamin E
      (primarily alpha-tocopheryl succinate), vitamin C (primarily sodium ascorbate)
      and carotenoids (primarily polar carotenoids) induce cell differentiation and
      growth inhibition to various degrees in rodent and human cancer cells by complex
      mechanisms. The proposed mechanisms for these effects include inhibition of
      protein kinase C activity, prostaglandin E1-stimulated adenylate cyclase
      activity, expression of c-myc, H-ras, and a transcription factor (E2F), and
      induction of transforming growth factor-beta and p21 genes. Furthermore,
      antioxidant vitamins individually or in combination enhance the growth-inhibitory
      effects of x-irradiation, chemotherapeutic agents, hyperthermia, and biological
      response modifiers on tumor cells, primarily in vitro. These vitamins,
      individually, also reduce the toxicity of several standard tumor therapeutic
      agents on normal cells. Low fat and high fiber diets can further enhance the
      efficacy of standard cancer therapeutic agents; the proposed mechanisms for these
      effects include the production of increased levels of butyric acid and binding of
      potential mutagens in the gastrointestinal tract by high fiber and reduced levels
      of growth promoting agents such as prostaglandins, certain fatty acids and
      estrogen by low fat. We propose, therefore, a working hypothesis that multiple
      antioxidant vitamin supplements together with diet and lifestyle modifications
      may improve the efficacy of standard and experimental cancer therapies.

PMID- 10067655
TI  - Survey of nutrition knowledge of Canadian physicians.
AB  - OBJECTIVES: Previous reports have indicated that physicians generally have little
      training in nutrition and a poor knowledge of the subject. A survey was carried
      out to determine the nutrition knowledge of physicians working in general
      practice. METHODS: A questionnaire with multiple-choice questions was mailed to
      248 physicians working in Alberta, Canada, mainly in Edmonton and Calgary. Non
      respondents received a second questionnaire and a phone call. RESULTS: Completed
      questionnaires were received from 36.1% (84 of 233 eligible physicians). The
      average correct response was 63.1%. The results indicate that physicians are
      generally aware of information which has been publicized in the medical press:
      which nutrients are antioxidants; the nutrient associated with the prevention of
      neural tube defects (folate); the preventive action of fruit and vegetables
      against cancer; the energy value of fat (9 kcals/g); and the recommended fat
      intake (under 30% of energy). By contrast they have a poor knowledge of other
      important topics in nutrition: the typical salt intake of Canadians; the
      association between excess protein intake and calcium loss; the type of dietary
      fiber helpful in lowering the blood cholesterol level (soluble fiber); and the
      nutrient which helps prevent thrombosis (omega-3 fat). CONCLUSIONS: These results
      support other data that physicians need more training in nutrition.

PMID- 10067656
TI  - Methodologies for using stable isotopes to assess magnesium absorption and
      secretion in children.
AB  - OBJECTIVE: To provide methodological information regarding the absorption and
      excretion of dietary magnesium by children and adolescents. METHODS: Recently,
      stable isotope techniques for assessing magnesium absorption and excretion have
      been developed which allow for these studies to be safely performed in subjects
      of all ages. In the report, we describe the dosing and sample requirements for
      such studies. RESULTS: Our data demonstrate that, after oral and intravenous
      dosing of isotopes, a complete 72-hour urine collection will allow for
      determination of fractional magnesium absorption. In our study, urinary, but not
      endogenous fecal magnesium excretion, was closely correlated with magnesium
      intake (r = 0.47, p = 0.02 vs r = 0.08, p = 0.69). As endogenous fecal magnesium
      excretion is small relative to urinary magnesium excretion, measurement of
      endogenous fecal magnesium excretion is not needed to make a reasonable estimate
      of net magnesium retention for most studies. Using high-precision analytical
      techniques, an intravenous dose of 25Mg of approximately 0.2 to 0.3 mg/kg would
      be adequate for absorption measurements. CONCLUSIONS: The cost and availability
      of isotopes and their analysis are such that it should be feasible for increasing
      numbers of investigators to make use of these techniques.

PMID- 10067657
TI  - Alterations in carbohydrate and lipid metabolism induced by a diet rich in
      coconut oil and cholesterol in a rat model.
AB  - OBJECTIVE: The type of dietary fat as well as the amount of cholesterol occurring
      in the diet have been associated with several metabolic disorders. Thus, the aim
      of the present study was to investigate the influence of a hypercholesterolemic
      diet enriched with coconut oil and cholesterol on carbohydrate and lipid
      metabolism in a rat model. METHODS: Twenty male Wistar rats weighing about 190 g
      were assigned to two dietary groups. One group received a semipurified control
      diet and the other was given a diet enriched in coconut oil (25% by weight) and
      cholesterol (1% by weight) for 26 days. RESULTS: Our results indicated a
      significant increase in serum total cholesterol (+285%; p<0.001), low-density
      lipoproteins (+154%; p<0.01), liver cholesterol (+1509%; p<0.001), as well as a
      significant increase in liver weight (+46%; p<0.001) in those rats fed the
      hypercholesterolemia-inducing diet as compared to controls. Moreover, a
      significant decrease in serum high-density lipoproteins (-67%; p<0.001),
      triacylglycerols levels (-33%; p<0.05), and abdominal fat weight (-39%; p<0.01)
      were found. The observed alterations in serum lipid and lipoprotein profile
      resembled a situation of type IIa hyperlipidemia in humans. Measurement of
      several enzymes concerned with lipid utilization revealed a significant increase
      in 3-hydroxy-3-methylglutaryl-CoA reductase activity (+68%; p<0.01) in the liver
      of animals fed the hypercholesterolemic diet, while a significant reduction in
      plasma lecithin-cholesterol acyltransferase activity (-66%; p<0.001) was found.
      The situation of hypoglycemia (-18%; p<0.05) was accompanied by lower levels of
      serum insulin (-45%; p<0.01) and liver glycogen (-30%; p<0.05) in the
      hypercholesterolemic rats. Furthermore, glucose utilization was altered since
      lower glucose-6-Pase (-33%; p<0.05) and increased glucokinase (+212%; p<0.001)
      activities in the liver were found in the rat model of hypercholesterolemia.
      CONCLUSION: These results provide new evidence that a diet-induced
      hypercholesterolemia in rats is associated with several adaptative changes in
      carbohydrate metabolism. These findings may be of importance not only considering
      the role of western diets on cholesterogenesis, but also in other metabolic
      disturbances involving lipid and carbohydrate metabolism.

PMID- 10067658
TI  - Effect of fermented milk (yogurt) containing Lactobacillus acidophilus L1 on
      serum cholesterol in hypercholesterolemic humans.
AB  - OBJECTIVE: Two controlled clinical studies were performed to examine effects of
      consumption of one daily serving of fermented milk (FM) (yogurt) on serum lipids.
      METHODS: In the first study, subjects were randomly allocated to FM containing
      Lactobacillus acidophilus L1 of human origin or to FM containing L. acidophilus
      ATCC 43211 of swine origin. In this single-blind study, subjects consumed one 200
      ml serving of FM daily for 3 weeks. The second study was a double-blind, placebo
      controlled, cross-over study. Subjects completed a 4-week first treatment, had a
      2-week washout, and completed a second 4-week treatment. In the second study
      subjects consumed FM containing L. acidophilus L1 or placebo FM over 4 weeks.
      RESULTS: In the first study, FM containing L. acidophilus L1 was accompanied by a
      2.4% (p<0.05) reduction of serum cholesterol concentration. In the second study,
      strain L1 reduced serum cholesterol concentration by 3.2% (p<0.05) in the first
      treatment period. In the second treatment period there were no significant
      changes in serum cholesterol concentration. Combined analysis of the two L1
      treatment studies demonstrated a 2.9% (p<0.01) reduction in serum cholesterol
      concentration. CONCLUSION: Since every 1% reduction in serum cholesterol
      concentration is associated with an estimated 2% to 3% reduction in risk for
      coronary heart disease, regular intake of FM containing an appropriate strain of
      L. acidophilus has the potential of reducing risk for coronary heart disease by 6
      to 10%.

PMID- 10067659
TI  - Heart murmurs, valvular regurgitation and electrical disturbances in copper
      deficient genetically hypertensive, hypertrophic cardiomyopathic rats.
AB  - OBJECTIVE: Rats with a genetic tendency to develop hypertensive, hypertrophic
      cardiomyopathy were fed copper-deficient diets and their cardiac responses were
      investigated. METHODS: Five male weanling rats of the Long-Evans and SHHF/Mcc
      fa(cp) strains were randomly selected to receive diets containing either adequate
      quantities of copper (94.5 micromol Cu/kg diet) or reduced quantities of copper
      (<15.8 micromol Cu/kg diet) for 6 weeks, (n=5 within each group). Echocardiograms
      and electrocardiograms were recorded and analyzed at the end of the 6-week
      interval. RESULTS: Electrocardiograms from copper deficient groups showed longer
      Q-T intervals and increased QRS amplitudes than controls. Both the copper
      deficient and control SHHF groups demonstrated significant QRS complex
      prolongation compared to Long-Evans rats. Echocardiography analysis showed
      significant increases in left ventricular area, free wall dimension, and
      myocardial cross-sectional areas in rats fed a copper deficient diet. The
      frequency of systolic cardiac murmurs increased in copper deficient rats and were
      related to the presence of valvular regurgitation as determined from
      echocardiography. DISCUSSION: However, the data do not suggest that a copper
      deficient diet fed to a strain of rats genetically susceptible to heart disease
      later in life, hastens or worsens the onset of cardiac disease. The genetic
      predisposition and copper-deficient states exert independent effects upon the
      heart.

PMID- 10067660
TI  - Measured energy expenditure of tube-fed patients with severe neurodevelopmental
      disabilities.
AB  - OBJECTIVE: To determine measured resting energy expenditure (REE) of
      nonambulatory tube-fed patients with severe neurological neurodevelopmental
      disabilities. METHODS: Twenty patients were prospectively studied. Only steady
      state indirect calorimetry measurements were taken. All measurements were
      conducted using a canopy system. Nutritional needs were met entirely by enteral
      feedings via a permanent ostomy. RESULTS: REE was widely distributed from 16
      kcals/kg/day to 39 kcals/kg/day. The mean REE (888+/-176 kcals/day) of the
      patients was significantly (p<0.01) lower than predicted as estimated by the
      Harris-Benedict equations (1081+/-155 kcals/day) and World Health Organization
      equations (1194+/-167 kcals/day). Fat-free mass (FFM) was the best parameter for
      predicting REE. Two predictive equations were developed that are not
      significantly biased and more precise (< or =15% error) than conventional
      predictive formulas. CONCLUSION: Conventional formulas for estimating energy
      expenditure are inaccurate and generally overestimate measured energy expenditure
      of nonambulatory patients with severe developmental disabilities.

PMID- 10067661
TI  - Relation of age and self-reported chronic medical condition status with dietary
      nutrient intake in the US population.
AB  - OBJECTIVE: To examine the association of nutrient intake with age and self
      reported chronic medical condition status in a large, nationally representative
      sample. METHODS: We used data from the Continuing Survey of Food Intakes by
      Individuals, 1989-1991. The analytic sample included subjects aged > or =25 years
      with 3 days of dietary data, and medical condition information (n=7,207). A
      positive response to having been informed by a doctor of having diabetes, heart
      disease, high blood pressure, cancer, osteoporosis, and stroke indicated the
      presence of chronic medical condition(s) (n=2,368). Sex-specific linear and
      logistic regression analyses adjusted for multiple covariates were used to
      examine the relation of age and morbidity status with nutrient intake. RESULTS:
      In men, age was associated with an increased risk of consuming <100% of the
      Recommended Dietary Allowance (RDA) of vitamin E, vitamin B12, calcium, zinc, and
      iron (p<0.05), and self-reported morbidity was associated with an increased risk
      of consuming <100% of the RDA of protein. Relative to men, women were more likely
      to report less than the RDA of most nutrients examined; however, neither age nor
      chronic disease status were associated with increased likelihood of reporting
      <100% of the RDA of any of the nutrients examined. In women, the probability of
      reporting <100% of the RDA of vitamin A, vitamin B6, folate, vitamin C, and iron,
      and in men, the probability of reporting <100% of the RDA of vitamin C, declined
      with age (p<0.05). No adverse effect of age and chronic disease interaction on
      intake of most nutrients was noted in men or women. CONCLUSIONS: Chronologic age
      and morbidity were associated with an increased risk of inadequate intake of
      several nutrients in free-living, independent men but not in women.

PMID- 10067662
TI  - L-carnitine improves glucose disposal in type 2 diabetic patients.
AB  - OBJECTIVE: Aim of the present study is to evaluate the effects of L-carnitine on
      insulin-mediated glucose uptake and oxidation in type II diabetic patients and
      compare the results with those in healthy controls. DESIGN: Fifteen type II
      diabetic patients and 20 healthy volunteers underwent a short-term (2 hours)
      euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L
      carnitine (0.28 micromole/kg bw/minute) or saline solution. Respiratory gas
      exchange was measured by an open-circuit ventilated hood system. Plasma glucose,
      insulin, non-esterified fatty acids (NEFA) and lactate levels were analyzed.
      Nitrogen urinary excretion was calculated to evaluate protein oxidation. RESULTS:
      Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine
      than with saline solution in the two groups investigated (48.66+/-4.73 without
      carnitine and 52.75+/-5.19 micromoles/kg(ffm)/minute with carnitine in healthy
      controls, and 35.90+/-5.00 vs. 38.90+/-5.16 micromoles/kg(ffm)/minute in diabetic
      patients). Glucose oxidation significantly increased only in the diabetic group
      (17.61+/-3.33 vs. 16.45+/-2.95 micromoles/kg(ffm)/minute, p<0.001). On the
      contrary, glucose storage increased in both groups (controls: 26.36+/-3.25 vs.
      22.79+/-3.46 micromoles/kg(ffm)/minute, p<0.001; diabetics: 21.28+/-3.18 vs.
      19.66+/-3.04 micromoles/kg(ffm)/minute, p<0.001). In type II diabetic patients,
      plasma lactate significantly decreased during L-carnitine infusion compared to
      saline, going from the basal period to the end-clamp period (0.028+/-0.0191
      without carnitine and 0.0759+/-0.0329 with carnitine, p<0.0003). CONCLUSIONS: L
      carnitine constant infusion improves insulin sensitivity in insulin resistant
      diabetic patients; a significant effect on whole body insulin-mediated glucose
      uptake is also observed in normal subjects. In diabetics, glucose, taken up by
      the tissues, appears to be promptly utilized as fuel since glucose oxidation is
      increased during L-carnitine administration. The significantly reduced plasma
      levels of lactate suggest that this effect might be exerted through the
      activation of pyruvate dehydrogenase, whose activity is depressed in the insulin
      resistant status.

PMID- 10067663
TI  - Dietary fructose but not starch is responsible for hyperlipidemia associated with
      copper deficiency in rats: effect of high-fat diet.
AB  - OBJECTIVE: To test the hypothesis that copper deficiency in rats may be
      hyperlipidemic only when the diets consumed contain nutrients which contribute to
      blood lipids such as fructose and high fat. METHODS: Weanling male Sprague Dawley
      rats were fed diets which contained either starch or fructose as their sole
      carbohydrate source. The diets were either inadequate (0.6 microg Cu/g) or
      adequate (6.0 microg Cu/g) in copper and contained either high (300 g/kg) or low
      (60 g/kg) fat. At the end of the 4th week the rats were killed. Livers were
      analyzed for copper content. Plasma was analyzed for cholesterol and triglyceride
      concentrations. RESULTS: High-fat diet did not increase blood lipids in rats fed
      a copper-deficient diet containing starch. In contrast, the combination of high
      fat diet with fructose increased blood triglycerides and fructose with copper
      deficiency resulted in a significant increases in blood cholesterol. CONCLUSIONS:
      Hyperlipidemia of copper deficiency in rats is dependent on synergistic effects
      between dietary fructose and copper deficiency and fructose and amount of dietary
      fat. Hyperlipidemia does not develop if starch is the main source of dietary
      carbohydrate in a copper-deficient diet even if a high-fat diet is fed.

PMID- 10067664
TI  - Nutritional status and dietary habits of Indian children from Alto Xingu (Central
      Brazil) according to age.
AB  - OBJECTIVE: To evaluate the nutritional status and dietary habits of children of
      the Alto Xingu, Central Brazil, according to age. SUBJECTS: 172 Indian children
      (<10 years of age) of Alto Xingu tribes. METHODS: Date of birth, sex, weight,
      height (NCHS reference) and questionnaire of dietary habits at the time of field
      work. RESULTS: Of the 103 children less than 5 years of age, 34% presented
      protein-energy malnutrition (PEM), according to Gomez's criteria, of which only
      2% with grade II malnutrition and no child presented severe PEM. In relation to
      the Z scores for the 172 children studied, it was observed that those younger
      than 1 year (n=25) presented weight for age (median, M=+0.43) and weight for
      height (M=+1.33) greater (p<0.05) than the children with ages between 12 and 60
      months (n=78) (weight for age, M=-0.54; weight for height, M=+0.29) and between
      60 and 120 months (n=69) (weight for age, M=-0.78; weight for height, M=+0.27).
      The height for age Z scores for the population studied showed a shift to the left
      in relation to the reference population in the three age groups (<12 months, M=
      0.95; 12 to 60 months, M=-1.22 and 60 to 120 months, M=-1.40). The mothers
      nursed, without exception, to the age of 24 months, and the frequency of
      breastfeeding decreased progressively to age 42 months. The introduction of solid
      foods started at the age of 6 months and after the 10th month all the children
      ate "beiju" (flat bread), fruit and fish. CONCLUSION: The nutritional status of
      Alto Xingu Indian children, in 1992, is adequate and similar to that previously
      observed between 1974 and 1980.

PMID- 10067665
TI  - DNA-mediated immunization to hepatitis B virus envelope proteins: preS antigen
      secretion enhances the humoral response.
AB  - In order to design optimized DNA vectors as genetic vaccines against infections
      with the hepatitis B virus (HBV) we investigated if secretion or retention of the
      viral antigens has an influence on the quality and quantity of the humoral immune
      response. Intramuscular injection of plasmid DNA encoding the HBV large L
      envelope protein, known to be retained within host cells, induced only a weak
      response in mice whereas a vector expressing the secretion-competent small S
      envelope protein elicited strong and sustained immunity. Immunization with
      rearranged envelope genes further demonstrated that secretion affects the
      magnitude of the immune response. In situ expression of modified small and middle
      envelope genes carrying C-terminally attached epitopes are derived from the preS1
      region of L generated high titers of preS1- and preS2-specific antibodies, unless
      antigen secretion was blocked. Accessibility of preS antigens to B-cells that can
      be achieved by generating extracellular forms of the envelope proteins is thus
      critical to elicit humoral responses. Such DNA constructs carrying preS1
      determinants are promising candidates for the development of multivalent HBV
      vaccines.

PMID- 10067666
TI  - Ending polio immunization: when and how are we sure that the needle is out of the
      haystack?

PMID- 10067667
TI  - Intradermal DNA immunization by using jet-injectors in mice and monkeys.
AB  - We have used spring powered jet injectors to deliver a solution of a naked DNA
      vaccine encoding the influenza hemagglutinin HA into the skin of mice and
      monkeys. We compared the immune responses induced by this needleless injection
      technique into the skin to the responses induced by a classical i.m.
      immunization. Both routes of immunization induced significant ELISA antibody
      titers and hemagglutination inhibition (HI) titers that were above the usual
      threshold values predictive of protection against influenza in mice and monkeys.
      In mice, both ways of immunization were equally efficient in inducing HA-specific
      CTL responses. Regarding antibody isotypes, the IgG1/IgG2a ratio was in favour of
      the IgG2a isotype for i.m. immunization and more balanced for i.d. immunization.
      The ability of the two injection techniques to induce immunity in mice did not
      correlate with transgene expression in the site of administration. In fact, local
      gene expression was 10-100 fold more important in the injected muscle as compared
      to the jet-injected skin when assessed by using the luciferase reporter system.

PMID- 10067668
TI  - Antibody responses and protection stimulated by sequential oral-parenteral
      immunization of mice with rotavirus.
AB  - Antibody responses and protection against shedding following oral challenge with
      murine rotavirus (EDIM) were determined in mice after sequential oral parenteral
      immunization. Oral immunization of 4-day-old BALB/c mice with live, heterologous
      rotavirus (RRV) stimulated serum rotavirus IgG but little serum or intestinal
      rotavirus IgA and small but significant (P < 0.001) reductions in EDIM shedding.
      Intraperitoneal immunization with inactivated EDIM at 29 days of age had similar
      effects. Sequential oral-parenteral immunization under these conditions
      stimulated small but significant (P < 0.001) increases in both rotavirus IgG and
      IgA titers and reduced shedding (P < 0.001) compared to individual immunizations.
      However, these responses were essentially additive, indicative of separate
      inductive/effector sites for mucosal and systemic immunity.

PMID- 10067669
TI  - The introduction of new vaccines into developing countries.
AB  - The development and introduction of new vaccines is a costly and time consuming
      process. Unfortunately, those most in need--individuals in developing countries-
      are the last to receive these powerful disease preventing products. From the time
      a vaccine is first licensed in a developed country to the time most of the poor
      in developing countries have access to the vaccine can be 20-30 years. This delay
      is unacceptable. There is a great need to reduce this time span. This paper
      examines five ways of reducing the time span. Each of the five is essential and
      achieving success on all five will require a heightened level of international
      effort and coordination.

PMID- 10067670
TI  - Enhanced protection against a lethal influenza virus challenge by immunization
      with both hemagglutinin- and neuraminidase-expressing DNAs.
AB  - The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or
      matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of
      these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or
      heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated
      twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1 microg of each
      component per mouse by particle-mediated DNA transfer to the epidermis (gene
      gun). Seven days after the last immunization, mice were challenged with a lethal
      homologous or heterologous virus and the ability of each DNA to protect the mice
      from influenza was evaluated by observing lung virus titers and survival rates.
      The administration of a plasmid DNA mixture of either (HA + NA) or (HA + NA + M1)
      provided almost complete protection against the PR8 virus challenge, and this
      protection was accompanied by high levels of specific antibody responses to the
      respective components. The degree of protection afforded in these groups is
      significantly higher than that in mice given either HA- or NA-expressing DNA
      alone, which provided only a partial protection against PR8 challenge or that in
      mice given M1-expressing DNA, which failed to provide any protection. In
      addition, both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a
      slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1)
      virus challenge, and this was accompanied by a relatively high level of cross
      reacting antibodies. Thus, there was no clear difference between the ability of
      the HA + NA and HA + NA + M1 plasmid DNA mixtures in providing protection against
      either a PR8 or heterologous virus challenge. These results suggest that in mice
      immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide
      the most effective protection against the virus challenge. The addition of the M 
      expressing plasmid DNA to this mixture does not enhance the degree of protection
      afforded.

PMID- 10067671
TI  - Expression of Epstein-Barr virus gp350 as a single chain glycoprotein for an EBV
      subunit vaccine.
AB  - There is currently no commercially available vaccine for Epstein Barr virus (EBV)
      related disease in humans. Since the EBV glycoprotein gp350/220 is the primary
      target for EBV-neutralizing antibodies following natural infection in humans and
      some forms of gp350/220 have been shown to protect against EBV-related disease in
      animal models, it is a likely candidate for an EBV subunit vaccine. We have made
      gp350/220 gene constructs that facilitate gp350 secretion from CHO cells and
      created splice site mutations in the gene that effectively prevent production of
      the gp220 species. Recombinant CHO cell gp350 (MSTOP gp350) is recognized by
      several different anti-gp350/220 monoclonal antibodies, and is also competent to
      bind to the cellular EBV receptor, CD21, suggesting that the recombinant protein
      is conformationally similar to wild-type EBV gp350/220. The MSTOP gp350 antigen
      raises high antibody titers in rabbits and these antibodies neutralize wild-type
      EBV. These properties make MSTOP gp350 a realistic candidate for a subunit
      vaccine against EBV-related disease.

PMID- 10067672
TI  - Cellular immune response of a varicella vaccine following simultaneous DTaP and
      VZV vaccination.
AB  - BACKGROUND: Chickenpox and zoster are an important cause of morbidity among
      children and adults. The ability of a new, thermostable vaccine to induce
      varicella-zoster-virus (VZV)-specific humoral and cell mediated immunity when
      given simultaneously with diphtheria-tetanus-acellular pertussis vaccine (DTaP)
      as a booster dose in the second year of life was investigated. METHODS: A new,
      temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart,
      Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV
      specific humoral and cell-mediated immunity was studied in the first 27 out of
      232 vaccinated children at 16-28 months of age, from blood samples drawn just
      before and six weeks after vaccination. VZV-specific antibody response, T-cell
      proliferation, cytokine production and expression of activation markers (CD25,
      HLADR) on T-cells were analyzed. RESULTS: Vaccination resulted in a significant
      rise of VZV-specific serum IgG titers and in a strong VZV-specific T-cell
      response in all vaccinated infants. Analysis of the expression of activation
      marker revealed activation of both CD4+-T-helper- and CD8+-T-cells. CONCLUSIONS:
      The varicella vaccine given simultaneously with DTaP produced strong B- and T
      cell responses alike. This is the first report to show that CMI to VZV is
      conferred to young children by vaccination with a temperature stable VZV vaccine.

PMID- 10067673
TI  - Lipopeptide particles as the immunologically active component of CTL inducing
      vaccines.
AB  - Using a bipalmitoylated lipopeptide consisting of an ovalbumin helper T-cell
      epitope covalently linked to an influenza virus cytotoxic T-lymphocyte (CTL)
      epitope, we addressed possible factors that may be critical for CTL induction.
      Antigen processing of lipopeptide appears to be required for T-cell induction
      since there was virtually no in vitro binding of lipopeptide to purified MHC
      molecules. A major portion of lipopeptide immunogenicity was due to its
      particulate nature inasmuch as CTL induction in mice correlated with insoluble
      lipopeptide constructs, whereas more soluble analogs were significantly less
      immunogenic. Immunohistological analysis of tissue from immunized animals
      revealed that lipopeptide migration from the s.c. injection site to the spleen
      could be detected as early as 1 h after immunization and cell-associated
      lipopeptide was observed on macrophages and dendritic cells, implicating both
      cell populations in the processing and presentation of lipopeptide particles to
      CTLs.

PMID- 10067674
TI  - Identification of murine cytotoxic T-lymphocyte epitopes of bovine herpesvirus 1.
AB  - Major histocompatibility complex (MHC) class I molecules present endogenously
      derived viral peptides to CD8+ cytotoxic T-lymphocytes (CTLs). The objective of
      this study was to identify the H-2Dd- and H-2Kd-restricted CTL epitopes of bovine
      herpesvirus 1 (BHV-1), based on the allele-specific peptide motifs (ASPMs) of the
      above class I molecules. Nine sequences conforming to the H-2Dd and H-2Kd ASPMs
      were identified on BHV-1 proteins, and the respective peptides were synthesized.
      Five of these peptides exhibited moderate to strong binding to the Dd molecule.
      CTLs generated by BALB/c mice immunized with BHV-1 proteins emulsified in a
      suitable adjuvant effectively lysed peptide-pulsed syngeneic targets, indicating
      that these epitopes were generated in vivo. Mice immunized with these peptides
      emulsified in a suitable adjuvant also developed anti-BHV-1 CTLs. These CTLs
      identified three veritable CTL epitopes among the "potential epitopes"
      synthesized based on the ASPMs. The elucidation of the CTL epitopes of BHV-1
      should aid in the development of efficacious vaccines against this virus.

PMID- 10067675
TI  - The adjuvants MF59 and LT-K63 enhance the mucosal and systemic immunogenicity of
      subunit influenza vaccine administered intranasally in mice.
AB  - Commercial influenza vaccines generate serum antibody, but not local IgA.
      Influenza vaccines that induce both serum and secretory antibody are more likely
      to protect against infection and disease progression. The adjuvants MF59 and LT
      K63 were tested intramuscularly and intranasally with subunit HA. In naive mice,
      intranasal adjuvant effect was more apparent when included with the first than
      second immunization. In previously infected mice, intranasal adjuvants had little
      effect on serum antibodies and were most effective for nasal antibodies after the
      second immunization. Overall, both adjuvants enhanced anti-HA IgA and IgG by
      intranasal vaccination whereas, by intramuscular vaccination, they only enhanced
      serum IgG.

PMID- 10067676
TI  - Immunogenicity of recombinant BCG producing the GRA1 antigen from Toxoplasma
      gondii.
AB  - Toxoplasmosis is a major parasitic disease, responsible for foetopathy in humans
      and domestic animals, especially sheep. Toxoplasma gondii infection generally
      protects immunocompetent hosts against subsequent reinfection, suggesting that
      efficacious vaccines can be developed against this disease. Excreted/secreted T.
      gondii antigens have previously been shown to provide immunoprotection in small
      rodents, and protective immunity is thought to be cell-mediated. Mycobacterium
      bovis BCG is known to be a good inducer of cellular immunity. In this study, we
      have developed a BCG strain which produces and secretes GRA1, one of the major
      excreted/secreted T. gondii antigens. This strain does not carry antibiotic
      resistance determinants and is therefore safe for the environment. The
      intraperitoneal immunisation of OF1 outbred mice with this BCG strain failed to
      induce GRA1-specific humoral or cellular immune responses and only conferred a
      very limited degree of protection against challenge with virulent T. gondii.
      However, in sheep immunised subcutaneously and boosted intravenously, this
      recombinant BCG strain induced GRA1-specific cell-mediated responses, as
      evidenced by the proliferation of peripheral blood mononuclear cells and by the
      production of IFN-gamma, although it failed to elicit GRA1-specific antibody
      responses. Following oocyst challenge infection, sheep immunised with recombinant
      BCG exhibited an abbreviated temperature response compared with controls,
      suggesting partial protection.

PMID- 10067677
TI  - Evaluation of novel aggregate structures as adjuvants: composition, toxicity
      studies and humoral responses.
AB  - Adjuvants are compounds that, when combined with an antigen, potentiate an immune
      response in an immunized species. There are numerous pathogens for which there
      are no protective vaccines and since alum is the only adjuvant licensed for use
      in humans, there is a clear need for more effective adjuvant preparations. In
      this study we describe the immunopotentiating properties of three novel molecular
      aggregate formulations based on tomatine (RAM1), a glycosylamide lipid (RAM2) and
      a fifth generation dendrimeric polymer (RAM3) respectively. These formulations
      were evaluated for their ability to augment antigen-specific antibody responses
      when administered with a soluble protein antigen. All three adjuvants were shown
      to be nontoxic to mice and elicited antigen-specific antibody responses. Of the
      three formulations, RAM1 was found to induce the highest titers of antibody;
      these were substantially higher than those induced by reference control
      adjuvants. RAM1 elicited antibodies of the IgG1 and IgG2a subclasses indicating,
      indirectly, that this adjuvant can stimulate Th2 and Th1 type immunity.

PMID- 10067678
TI  - Human antibody responses to A and C capsular polysaccharides, IgA1 protease and
      transferrin-binding protein complex stimulated by infection with Neisseria
      meningitidis of subgroup IV-1 or ET-37 complex.
AB  - The protein sequences of the IgA1 protease, TbpA and TbpB proteins differ between
      meningococci representative of serogroup A, subgroup IV-1 from epidemic disease
      in The Gambia and serogroup C, ET-37 complex from endemic disease in Mali. The
      uniformity of restriction endonuclease sites was determined for the iga, tbpA and
      thpB genes among strains of both clonal lineages. Rare isolates had acquired a
      variant thpAB operon by horizontal genetic exchange but all other strains were
      uniform within each clonal lineage. The quantitative levels of IgG to capsular
      polysaccharide, IgA1 protease and TBP complex were measured in paired acute phase
      and convalescent phase sera from The Gambia and from Mali using antigens from the
      homologous clonal lineages. IgG levels to these antigens were also measured in
      paired sera from healthy Gambians who permanently carried meningococci in the
      nasopharynx or did not. The results showed that disease stimulated IgG to each
      antigen in Mali and to all but TBP complex in The Gambia. Similarly, higher
      levels of IgG were found in sera from permanent carriers than in sera from
      permanent non-carriers. Acute phase sera from Mali contained low levels of IgG to
      C capsular polysaccharide (geometric mean value of 0.3 microg ml(-1)) while such
      sera from The Gambia contained higher and potentially protective levels of IgG to
      A polysaccharide (geometric mean of 5.5 microg ml(-1)). The concentrations of IgG
      to TBP complex in acute phase sera were higher and IgG to IgA1 protease was even
      higher, suggesting that intermediate levels of IgG to these proteins do not
      protect against disease.

PMID- 10067679
TI  - Epidemiology of rotavirus in infants and protection against symptomatic illness
      afforded by primary infection and vaccination.
AB  - This study assessed the frequency of symptomatic and asymptomatic primary and
      secondary infections with rotavirus in children under 24 months and determined
      protection against symptomatic illness afforded by rhesus and human-rhesus
      rotavirus reassortant vaccines. Successive cohorts of children (n 236) were
      followed through five winter rotavirus seasons with cultures of each reported
      episode of diarrheal disease and serologic determination of rotavirus exposure on
      paired sera bracketing the winter. An average of 46% of children experienced
      rotavirus infection in each season with almost all infected by two years of age.
      The relative risk of rotavirus associated gastroenteritis in naive children
      versus naturally immune children was 2.4 (1.1, 5.3). The relative risk of
      rotavirus associated gastroenteritis in naive children versus vaccinees was 4.1
      (1.6, 10.7). In a community with predominantly serotype G1 rotavirus rhesus
      rotavirus-based vaccines are as protective against rotavirus gastroenteritis as
      prior natural infection.

PMID- 10067680
TI  - Human IgG subclass responses in relation to serum bactericidal and opsonic
      activities after immunization with three doses of the Norwegian serogroup B
      meningococcal outer membrane vesicle vaccine.
AB  - Ten adult volunteers, with low prevaccination levels of serum IgG antibodies
      against meningococcal antigens (< 1 microg ml(-1)), received three doses of the
      Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine
      intramuscularly at weeks 0, 6 and 46. Anti-OMV IgG subclass responses were
      measured and compared with serum bactericidal activity (SBA) and opsonic activity
      against the vaccine strain 44/76. All vaccinees showed an IgG1 antibody response
      after each vaccine dose. The vaccine-induced median serum IgG1 antibody levels
      were 16, 17 and 18 microg ml(-1) 2-6 weeks after the first, second and third
      dose, respectively. Three vaccinees showed a weak IgG3 response after the first
      dose, whereas 8 and 9 showed a response after the second (median = 10 microg ml(
      1)) and third dose (median = 10 microg ml(-1)), respectively. Low levels of anti
      OMV IgG2 antibodies were found, whilst specific IgG4 antibodies were only
      detected for one vaccinee. The vaccine induced at least a fourfold increase in
      SBA titre in 8 vaccinees after the first dose, in 9 vaccinees after 2 doses and
      in all vaccinees after 3 doses. A positive correlation was found between IgG1
      subclass antibody levels and SBA (r = 0.62, P < 0.0001). Elevated
      opsonophagocytic activity, measured as respiratory burst (RB), was observed in
      all vaccinees after one vaccine dose and usually increased after 2 and 3 doses. A
      strong positive correlation was found between IgG1 antibody levels and RB (r =
      0.76, P < 0.0001). In conclusion, we have shown that systemic meningococcal OMV
      vaccination in adult vaccinees mainly induced IgG1 antibodies which correlated
      with bactericidal and opsonic activity, but also a considerable amount of IgG3
      antibodies, which, in contrast to the IgG1 response, was induced only after 2 or
      3 vaccine doses and declined more rapidly.

PMID- 10067681
TI  - Varicella vaccination of health-care workers.
AB  - The objective of this open study was to evaluate the response of non-immune
      health-care workers to two doses of live attenuated varicella vaccine given two
      months apart. One hundred subjects (58 females; aged 17-49 yr, mean 22.8 yr)
      received two doses of varicella vaccine. Blood samples for antibody estimation
      were taken before vaccination, 2 months after the first dose and 6 weeks after
      the second dose. Reactions were recorded daily in diaries by the vaccinees and
      controlled by telephone contacts by the investigators. Ninety-four of 99
      vaccinees (94.9%, 95% CL 88.6, 98.3) had detectable antibodies after the first
      dose [titers 4-1024, geometric mean titer (GMT): 53.2 (95% CL 42.4, 66.8)]. After
      the second dose, all vaccinees had antibodies (100%, 95% CL 96.6, 100.0) [titers
      32-2048, GMT: 235.6 (95% CL 199.0, 278.8)]. Mild reactions limited to the
      injection site occurred in 1 in 4 subjects after each dose. Vesicular rashes
      occurred in one subject after the 1st dose and in 3 subjects after the 2nd dose,
      1 subject was febrile (38.2 degrees C) after the 1st dose. Eighty-one subjects
      were retested 12 months after the second vaccination. Three had become
      seronegative (one developed mild varicella 2 months later). Two had boosted their
      titers (one after mild clinical varicella 1 month earlier, the other after close
      contact with clinical cases). The GMT of the group had fallen to 83.6 (95% CL
      65.4, 106.8). The identification and vaccination of seronegative health-care
      workers is safe and efficient, and will benefit the workers themselves and the
      communities in which they work.

PMID- 10067682
TI  - Expression of a pilin subunit BfpA of the bundle-forming pilus of
      enteropathogenic Escherichia coli in an aroA live salmonella vaccine strain.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major cause of childhood diarrhea
      in developing countries and is a leading cause of severe diarrheal illness among
      Brazilian infants. As one approach to constructing a vaccine candidate against
      diarrhea caused by EPEC, we evaluated whether the pilin subunit (BfpA) of the
      bundle-forming pilus (BFP) could be expressed by a live Salmonella vaccine
      strain. Several copies of the coding region of BfpA (bfpA) were amplified by PCR
      from a preparation of the EAF plasmid of EPEC strain B171 and cloned into plasmid
      vectors. An intact copy of bfpA was subcloned into the heat inducible prokaryotic
      expression vector pCYTEXP1, and the resulting pBfpA was used to transform the
      aroA S. typhimurium strain SL3261, generating SL3261(pBfpA). The recombinant
      vaccine strain was able to express, but not to process, rBfpA as evidenced by a
      prominent 21 kDa protein that crossreacted with anti-BFP antiserum found only in
      extracts of heat-treated SL3261(pBfpA), but not in strains of untreated
      SL3261(pBfpA) or SL3261 not carrying the plasmid. Furthermore, rBfpA accumulation
      was not toxic to the Salmonella host, as evidenced by similar plating
      efficiencies between induced and uninduced strains of SL3261(pBfpA). Finally,
      SL3261(pBfpA) orally administered to BALB/c mice was capable of eliciting a
      sustained and vigorous humoral immune response to BfpA, achievable even with a
      single oral dose of approximately 10(9) organisms. Therefore, this pilin product
      may serve as a potential immunogen as part of a live combined vaccine strategy to
      prevent two of the major public health problems in Brazil--salmonellosis and EPEC
      childhood diahrrea.

PMID- 10067683
TI  - Pathogenicity of tick-borne encephalitis virus isolated in Hokkaido, Japan in
      mouse model.
AB  - The pathogenic characteristics of tick-borne encephalitis (TBE) virus strain
      (Oshima 5-10) isolated from a sentinel dog in Hokkaido, Japan, was compared by
      use of a mouse model with several inoculation routes to other strains of TBE
      virus (the Far Eastern subtype; Sofjin strain and the Western subtype;
      Hochosterwitz strain) and TBE complex virus (Langat virus; TP-21 strain). The
      degree of neuroinvasiveness of the strains in mice subcutaneously (s.c.)
      inoculated was Sofjin equaled Hochosterwitz which was greater than Oshima and TP
      21, respectively. Neurovirulence, as determined after intracerebral inoculation
      was Sofjin > Oshima = Hochosterwitz > TP-21. Virus replication in the brains of
      mice s.c. or intracerebrally inoculated with Oshima strain was slower and of
      lower titer than that of Sofjin strain. Histopathological findings indicated that
      subarachnoid infiltration of mononuclear cells prior to necrosis of the cerebrum
      was characteristic in Oshima strain. These findings indicated that the Oshima
      strain possessed a pathogenic potential common to TBE viruses and is less
      virulent for mice as compared with the two other TBE strains examined.

PMID- 10067684
TI  - Mucosal immunogenicity and adjuvanticity of cholera toxin in swine.
AB  - The oral immunogenic and adjuvant properties of cholera toxin (CT) and its
      nontoxic B subunit (CT-B) were assessed in swine. Both whole CT and CT-B are oral
      immunogens in swine and CT is relatively more potent. Oral administration of 100
      microg of CT resulted in a greater immune response than 1 mg of CT-B as measured
      by anti-CT-B IgA, IgG and IgM in local (jejunum) and distant (oral cavity)
      mucosal sites, and in systemic sites including blood and spleen. Lower doses of
      CT were potent adjuvants for the response to CT-B, but did not induce detectable
      immunity alone. The predominant response to oral CT-B administered with CT was
      intestinally produced and secreted IgA, with about 2500 per 10(6) jejunal lamina
      propria cells producing anti-CT-B IgA in immunized animals. While CT is a potent
      adjuvant for CT-B, its ability to act as adjuvant for heterologous proteins is
      more restricted. 50 microg of CT in combination with 1 mg of CT-B did not induce
      antibodies to 25 mg of coadministered KLH. However, chemical linking of ovalbumin
      to CT-B and coadministration with CT resulted in a detectable antibody response
      to ovalbumin. These results suggest that CT is immunogenic and is a potent
      adjuvant for CT-B in swine and that the induction of mucosal immunity to
      heterologous antigens may require specific targeting to the gut-associated
      lymphoid tissues.

PMID- 10067685
TI  - Efficacy of an ovine caseous lymphadenitis vaccine formulated using a genetically
      inactive form of the Corynebacterium pseudotuberculosis phospholipase D.
AB  - Caseous lymphadenitis (CLA) is an economically significant disease of sheep
      caused by the gram-positive bacterium Corynebacterium pseudotuberculosis. CLA
      vaccines are currently formulated using formalin inactivated culture supernatants
      that are rich in the C. pseudotuberculosis phospholipase D (PLD) exotoxin. One
      alternative to chemical detoxification is to inactivate the PLD genetically. This
      procedure not only provides a means to remove an onerous chemical treatment step
      but also the opportunity to increase gene expression, therefore improve protein
      yields. Using site-specific mutagenesis the C. pseudotuberculosis PLD was
      inactivated by substituting a serine residue at histidine 20 within the enzyme
      active site. CLA vaccine formulated using genetically inactivated PLD protected
      44% of sheep against C. pseudotuberculosis challenge compared with 95% protection
      offered by the formalin inactivated preparation. Since there was no apparent
      difference in immune response mounted by vaccinated sheep the reason for this
      variation in vaccine efficacy remains unclear. Although genetic inactivation can
      be a convenient means to produce toxoid vaccines its use to develop a new CLA
      vaccine provided no net benefit over the conventional formulation.

PMID- 10067686
TI  - The effect of formalin-inactivated vaccine on respiratory disease associated with
      bovine respiratory syncytial virus infection in calves.
AB  - The effect of vaccination with a formalin-inactivated, alum-precipitated (FI),
      bovine respiratory syncytial virus (BRSV) vaccine on BRSV induced respiratory
      disease in calves was investigated. Six month old BRSV-naive calves were
      vaccinated with either a FI, a modified live virus (MLV), or virus antigen
      negative control vaccine (n = 4 per group). One month after the second
      vaccination, the calves were aerosol challenged with lung wash from a newborn
      calf infected with a field isolate of BRSV. Moderate to severe clinical disease
      occurred in all calves. Calves that received FI vaccine had a significantly
      earlier (day 2 vs. day 4-5) onset of pyrexia and dyspnea (P < 0.05). Pulmonary
      lesions, consisting of cranioventral atelectasis and dorsal emphysema, occurred
      in all groups. Two calves that received MLV, and three that received FI vaccine,
      had reduced pneumonic lung area relative to controls. Vaccination with the FI
      vaccine resulted in more rapid onset of clinical disease, but ultimately, reduced
      pulmonary pathology in most recipients.

PMID- 10067687
TI  - Sequence analysis of Pasteurella multocida major outer membrane protein (OmpH)
      and application of synthetic peptides in vaccination of chickens against
      homologous strain challenge.
AB  - Pasteurella multocida major outer membrane protein (OmpH) has been previously
      characterized as a porin. The native OmpH from strain X-73 (serotype 1) but not
      recombinant protein from Escherichia coli induced homologous protection in
      chickens. In this study OmpH sequences from 15 P. multocida serotypes as well as
      the CU vaccine strain were compared by sequence alignment and revealed high
      homology, with major variations confined to two discrete regions which were
      correspondingly predicted as two largest external loops. Secondary structures of
      OmpHs were predicted by sequence alignment of OmpHs with well defined porins and
      analyses of amphiphilicity, hydrophobic moment and antigenic index plots. Several
      synthetic peptides derived from predicted loop 2 and loop 5 of X-73 OmpH were
      synthesized as vaccine candidates. Vaccination studies in chickens showed that
      the cyclic synthetic peptide (Cyclic-L2) mimicking the predicted loop 2 induced
      70% protection in chickens against strain X-73 challenge. This is the first
      report that a synthetic peptide mimicking the conformational epitopes of a native
      protein provide practical protection in target animal against bacterial
      infection.

PMID- 10067688
TI  - Complete protection of mice from respiratory syncytial virus infection following
      mucosal delivery of synthetic peptide vaccines.
AB  - We have previously shown that intraperitoneal immunization of BALB/c mice with
      the 14 amino-acid long synthetic peptides G/174-187 and BG/174-187, representing
      the region 174-187 of the G-glycoprotein from human (H) and bovine (B)
      respiratory syncytial virus (RSV), respectively, completely protects animals from
      infection with the corresponding virus. A current goal in vaccine development
      being the delivery of noninvasive protective antigens via mucosal surfaces, we
      have evaluated the immunogenicity and protective efficacy of the two peptides
      when administered to mice by the intranasal (i.n.) route in the presence or
      absence of the cholera toxin (CT) as a mucosal adjuvant. The two peptides given
      alone induced the production of RSV-specific circulating IgG, as revealed by
      ELISA titers of immune sera. When the peptides were administered intranasally
      with CT, the higher IgG antibody titer which was induced was within the same
      order of magnitude as that obtained following i.n. immunization with live RSV or
      intraperitoneal injection with the peptides, thus demonstrating the stimulatory
      effect of the CT adjuvant. Moreover, although the peptides fail to induce a
      detectable level of secretory IgA, all animals immunized i.n. with peptide BG/174
      187 (plus or minus CT) and all those immunized with peptide G/174-187 mixed with
      CT were completely resistant to infection by the corresponding virus. To our
      knowledge, this is the first study reporting that complete protection against a
      natural pathogen can be elicited by mucosally delivered synthetic peptides. This
      supports the usefulness of synthetic peptides in prophylactic vaccination.

PMID- 10067689
TI  - Mild illness at or after measles vaccination does not reduce seroresponse in
      young children.
AB  - We analyzed data from a randomized trial of AIK-C, high-titre (EZ-H) or medium
      titre EZ (EZ-M) vaccines in 3.5 and 6 month old infants in Kinshasa, Zaire, in
      which the occurrence of rhinorrhoea, cough, diarrhoea, fever, conjunctivitis or
      rash was monitored for 15 days post-vaccination (including the day of
      vaccination, day 0). We compared sero-response at 6 weeks and 6 months post
      vaccination among children with and without mild illness at or after vaccination.
      Seroresponse tended to be higher in children with mild illness after vaccination
      than those without, whether days 0-7 or 8-15 were examined. For most symptoms,
      these differences did not reach statistical significance after adjusting for
      prevaccination maternal antibody level. However, in the EZ-M group, the
      proportion of children attaining at least the median post-vaccination antibody
      level was significantly higher in children with rhinorrhoea in days 0-7 post
      vaccination than those without (adjusted odds ratio 2.6, 95% CI 1.08-6.27), as
      was that among children with at least one symptom in days 0-7 compared with
      children with no symptoms (adjusted OR 4.55, 95% CI 1.18-17.57). There were no
      significant differences in post-vaccination antibody levels among children with
      symptoms compared either to those without the specific symptom or those with no
      symptoms. Fever on the day of vaccination or at home visits on 7, 10 or 14 days
      post-vaccination, did not affect seroconversion or GMTs. Regression models showed
      no relation between the cumulative number of days with symptoms and antibody
      increase after vaccination. Analysis of antibody levels at 6 months post
      vaccination showed no consistent differences according to presence or absence of
      symptoms. These findings provide further strong support to recommendations that
      mild illness is not a reason to delay measles vaccination.

PMID- 10067690
TI  - Seroprevalence and determinants of diphtheria, tetanus and poliomyelitis
      antibodies among adults in Berlin, Germany.
AB  - The immunity levels against diphtheria, tetanus and poliomyelitis were
      investigated among blood donors (n = 2079) in Berlin. Of all participants, only
      60% had full, long-term protection against diphtheria, 72% against tetanus, 87%
      against poliomyelitis type 1, 77% against poliomyelitis type 2 and 73% against
      type 3. There was a striking decrease of tetanus and diphtheria immunity levels
      by age. Immunity levels against tetanus were higher among males, whereas females
      were better protected against poliomyelitis. After adjusting for confounding
      effects in logistic regression diphtheria immunity in those aged <40 years was
      significantly higher in participants from East-Berlin, whereas the immunity
      levels against poliomyelitis were higher in West-Berlin. These differences
      reflect the different vaccination policies in East-Germany and West-Germany
      before 1989. There is a need to improve the immunity levels of the adult
      population in Berlin.

PMID- 10067691
TI  - Vaccination with the plasminogen activator from Streptococcus uberis induces an
      inhibitory response and protects against experimental infection in the dairy cow.
AB  - Two antigens comprising either concentrated culture filtrate containing the
      plasminogen activator, PauA (total antigen) or the same preparation from which
      PauA had been selectively removed by incubation with a PauA-specific monoclonal
      antibody and immobilisation on Protein-G agarose (depleted antigen) were combined
      with either Freund's incomplete adjuvant (FIA) or a commercially used adjuvant
      (SB62) and used to vaccinate dairy cows by a subcutaneous route. Immunisation of
      four animals with depleted antigen combined with FIA conferred no protection to
      mastitis following intramammary challenge with S. uberis 0140J. However,
      immunisation of two groups of four animals with the total antigen combined with
      either FIA or SB62 induced protection in 3 out of 8 and 5 out of 8 similarly
      challenged quarters, respectively. Protection corresponded to the production of
      an inhibitory antibody response to PauA.

PMID- 10067692
TI  - IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA
      vaccine.
AB  - Cytokines are powerful regulators of the immune response. In this study, an HIV-1
      envelope DNA vaccine and interleukin 15 (IL-15) expression plasmid were
      intranasally administered to mice. A significant increase in the HIV-1-specific
      DTH response and CTL activity, and decrease in the serum IgG/IgG2a ratio was
      observed in the group which received DNA vaccine and IL-15 expression plasmid
      compared to DNA vaccination alone. Restimulated immune lymphoid cells from mice
      which received both agents showed enhanced production of interferon-gamma (IFN
      gamma) and reduced secretion of IL-4. However, administration of DNA vaccine with
      IL-15 and IL-2 or IL-12 expression plasmids did not alter the effect of IL-15
      expression plasmid on the DNA vaccine. These results indicate that intranasal
      administration of DNA vaccine and IL-15 expression plasmid is capable of
      enhancing the T helper type 1 (Th1) dependent HIV-1-specific cell-mediated
      immunity, and that the IL-15 and IL-2 or IL-12 expression plasmids may not have a
      synergistic effect on the immune response induced by DNA vaccine in vivo.

PMID- 10067693
TI  - Vaccination against tick-borne encephalitis under therapeutic immunosuppression.
      Reduced efficacy in heart transplant recipients.
AB  - Patients after organ transplantation are at an increased risk of microbial
      infections and might benefit from active vaccination. Due to therapeutic
      immunosuppression the efficacy of immunizations is, however, reduced and
      difficult to predict. Efficacy of vaccination against tick-borne encephalitis
      (TBE) using an abbreviated immunization schedule was compared in 31 heart
      transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation:
      53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls.
      TBE vaccination was well tolerated by the transplant recipients; spectrum and
      frequency of adverse events were similar to controls. In the transplant patients,
      seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post
      vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001)
      were markedly reduced in comparison to the control group. No clinical or
      demographic predictors of vaccination success could be established in the
      transplant patients. Due to the limited efficacy, TBE vaccination cannot be
      recommended as a routine procedure in heart transplant recipients at risk of TBE
      virus infection. TBE vaccination may be performed safely in selected cases, but
      repeated titre controls to confirm vaccination success would be required.

PMID- 10067694
TI  - Priming effect, immunogenicity and safety of an Haemophilus influenzae type b
      tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis
      (DTaP) combination vaccine administered to infants in Belgium and Turkey.
AB  - To evaluate the priming effect, immunogenicity and safety of an Haemophilus
      influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus
      acellular (two component) pertussis (DTaP) combination vaccine, a randomized,
      comparative study was conducted in two centers, one in Belgium and one in Turkey.
      A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly
      received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138)
      received DTaP and PRP-T vaccines reconstituted immediately prior to injection at
      3, 4 and 5 months of age, and are referred to as the combined, short schedule
      group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but
      injected at different sites according to the same schedule, and are referred to
      as the associated, short schedule group (As-S). The third group (N = 137) also
      received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are
      referred to as the associated, long schedule group (As-L). The As-L group allowed
      for serological bridging with a Senegalese two-component pertussis vaccine
      efficacy trial, using the same batch of DTaP vaccine. Children of both short
      schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster
      dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the
      vaccines did not affect the immune response to the antigens included in the DTaP
      vaccine. The immune response to Hib capsular polysaccharide, however, was
      significantly lower after combined administration (Co-S group) than after
      associated (As-S group) administration (P < 0.0001), with a similar trend among
      both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02
      microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the
      unconjugated PRP induced a vigorous and similar anamnestic response in both
      groups. Belgian infants showed a significantly lower immune response to all
      antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar
      trend among each study group. In all groups, the incidence of adverse events was
      lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of
      systemic reactions were observed in the Belgian population, possibly due to
      differences in reporting practice. Our results indicate (1) that the combination
      vaccine, DTaP//PRP-T, represents an important improvement over the existing
      uncombined vaccines; (2) that immunogenicity studies should include at least one
      booster injection to evaluate priming effects by combined vaccines; and (3) that
      it is feasible and valuable to co-randomize combination vaccine studies in
      sufficiently different geographical areas and child populations.

PMID- 10067695
TI  - Enhanced CD8+ T cell response to HIV-1 env by combined immunization with
      influenza and vaccinia virus recombinants.
AB  - With the aim to determine if immunization with two different live recombinant
      viral vectors could lead to an enhancement of the cellular immune response to HIV
      1 antigens, we have characterized the CD8+ T cell response elicited against the
      V3 loop epitope from HIV-1 env protein in Balb/c mice immunized with either: a
      recombinant influenza virus (Flu-Env) expressing the V3 loop epitope from HIV-1
      strain IIIB, a vaccinia virus recombinant (VV-Env) expressing the complete HIV-1
      IIIB env protein, or a combination of both. The CD8+ T cell response, measured by
      the ELISPOT assay, in animals primed with Flu-Env and boosted with VV-Env was 5
      to 6 times higher than in animals inoculated with either Flu-Env or VV-Env alone.
      Similar results were obtained with recombinant viruses expressing the V3 loop
      epitope or the complete env protein, respectively, from the MN strain of HIV-1.
      Our results indicate that the use of two different live vectors for priming and
      boosting has a synergistic effect on the immune response against HIV-1, and could
      represent a novel vaccination strategy against AIDS.

PMID- 10067696
TI  - The use of combination vaccinia vaccines and dual-gene vaccinia vaccines to
      enhance antigen-specific T-cell immunity via T-cell costimulation.
AB  - Several recombinant vaccinia viruses are currently being evaluated to induce
      antigen-specific immunity to a variety of infectious disease agents and tumor
      associated antigens. T-cell costimulation is extremely important in enhancing T
      cell responses, and recombinant vaccines have now been shown to be effective
      vectors to express a range of these molecules. Both combination vaccines (an
      admixture of a recombinant vaccinia virus expressing a specific target antigen
      and a recombinant vaccinia virus expressing a costimulatory molecule) and dual
      gene vaccines expressing both transgenes on the same vector have been shown
      capable of effectively enhancing antigen-specific responses via T-cell
      costimulation. In this report, we compare for the first time the use of both
      types of approaches to enhance antigen-specific T-cell responses, and we
      demonstrate the importance of route of vaccine administration and vaccine dose in
      attaining optimal T-cell responses. These studies should have direct bearing on
      the design of vaccine clinical trials for infectious agents and/or tumor
      associated antigens, in which T-cell costimulatory molecules will be employed to
      enhance antigen-specific T-cell responses via the use of either combination or
      dual-gene vaccinia vaccines.

PMID- 10067697
TI  - Safety and immunogenicity of recombinant Bacille Calmette-Guerin (rBCG)
      expressing Borrelia burgdorferi outer surface protein A (OspA) lipoprotein in
      adult volunteers: a candidate Lyme disease vaccine.
AB  - This phase I clinical trial was designed to determine the feasibility of using
      rBCG as a live bacterial vaccine vector for the outer surface protein A (OspA) of
      Borrelia burgdorferi and as model for other vaccines based on a rBCG vector. To
      construct the vaccine, a signal peptide derived from a mycobacterial lipoprotein
      was used to direct the export, and membrane-associated surface expression, of
      OspA in a standard strain of BCG (Connaught). The rBCG OspA vaccine was safe and
      immunogenic in several animal species, and protective in a mouse model of Lyme
      borreliosis. An intradermal injection (0.1 ml) of rBCG OspA was administered to
      24 healthy adult volunteers sequentially at one of four dose levels, ranging from
      2.0 x 10(4) CFU to 2 x 10(7) CFU, using a dose-escalation design. All volunteers
      were initially PPD-skin test and OspA antibody negative, and they were monitored
      for 2 years after immunization. Three volunteers had mild flu-like reactions 1-2
      days after vaccination. Local ulceration and drainage at the site of injection,
      which occurred in 50% and 83% of volunteers in the two highest dose groups,
      persisted for 1-70 days before the ulcers healed. Most of the drainage samples
      yielded rBCG colonies that contained the OspA plasmid. Thirteen of 24 vaccinees,
      principally in the two highest dose groups, converted their PPD skin tests from
      negative to positive. None of the 24 volunteers developed OspA antibody. In
      conclusion, the current rBCG vaccine construct, the first such construct tested
      in humans, had a safety profile comparable to that of licensed BCG, but it did
      not elicit primary humoral responses to the vectored antigen.

PMID- 10067698
TI  - A historical and molecular phylogeny of BCG strains.
AB  - Bacillus Calmette-Guerin (BCG) is the name given to a family of vaccines derived
      in 1921 by the in-vitro attenuation of Mycobacterium bovis. Subsequently, BCG
      seed lots were distributed globally, and both phenotypic and genotypic
      differences between strains have been described. As a step to understanding BCG
      diversity, we have reviewed the English and French historical record on 13
      strains and DNA was extracted from these strains for restriction-fragment-length
      polymorphism study. The written record suggests "early strains" obtained from the
      Pasteur Institute between 1924 and 1926 and "later strains" obtained after 1931.
      Molecular typing resulted in 3 clades, based on variability in IS6110-typing and
      the presence of mpt64 gene. With two exceptions, these clades correspond with
      strains obtained in 1924-26 (IS6110-2/mpt64+), 1926-31 (IS6110-1/mpt64+), and
      1931 or later (IS6110-1/mpt64-) This analysis demonstrates that BCG has undergone
      genetic changes since 1921, consistent with ongoing in-vitro evolution.

PMID- 10067699
TI  - Recombinant, attenuated Salmonella typhimurium stimulate lymphoproliferative
      responses to SIV capsid antigen in rhesus macaques.
AB  - Recombinant bacteria are useful vectors for delivering foreign antigens to
      mucosal surfaces and may elicit immune protection against sexually-transmitted
      pathogens. Recombinant, attenuated Salmonella typhimurium expressing the Simian
      Immunodeficiency Virus capsid protein (p27) were given to rhesus macaques by
      intragastric intubation. This route of immunization was compared with
      intramuscular injection of soluble p27 in adjuvant, and with immunization
      protocols that combined intragastric and intramuscular antigen exposures.
      Recombinant Salmonella stimulated p27-specific lymphoproliferative responses that
      were present transiently in peripheral blood, and were recalled easily by booster
      immunizations. Intramuscular p27 injection elicited strong serum antibody
      responses, but only low level capsid-specific proliferative responses.
      Recombinant Salmonella immunization elicited low levels of p27-specific
      antibodies in serum and did not suppress subsequent responses to parenteral
      immunization. Intragastric immunization of macaques with recombinant Salmonella
      typhimurium was safe and induced immune responses specific for the expressed,
      foreign antigen.

PMID- 10067700
TI  - The effect of pre-existing adenovirus-specific immunity on immune responses
      induced by recombinant adenovirus expressing glycoprotein D of bovine herpesvirus
      type 1.
AB  - We investigated whether pre-existing adenovirus-specific immunity influenced the
      development of immunity to a foreign antigen expressed by recombinant adenovirus.
      Active adenovirus-specific immunity was induced in cotton rats by i.n.
      administration of wild type human adenovirus type 5 (HAd5) two weeks before
      immunisation with a HAd5 vector expressing the glycoprotein D (gD) of bovine
      herpesvirus type 1 (gD-dE3 recombinant adenovirus). Active adenovirus-specific
      immunity inhibited gD-specific immune responses, following either i.n. or
      gastrointestinal immunisation with gD-dE3. An inhibitory effect was present even
      if infection with HAd5 and immunisation with gD-dE3 were 13 weeks apart. Passive
      transfer of adenovirus specific antibodies to cotton rats one day before
      immunisation, however, did not significantly inhibit gD-specific immune responses
      induced by i.n. immunisation with gD-dE3. Repeated administration of an
      adenovirus vector, therefore, may have a limited ability to deliver antigen,
      while passive immunity to adenovirus may not interfere with the success of
      immunisation.

PMID- 10067701
TI  - Intranasal or subcutaneous co-administration of recombinant cholera toxin B
      subunit stimulates only a slight or no level of the specific IgE response in mice
      to tetanus toxoid.
AB  - Whether recombinant cholera toxin B subunit (rCTB) co-administered intranasally
      or subcutaneously with aluminium-non-adsorbed tetanus toxoid (nTT) can induce the
      production of tetanus toxoid (TT)-specific IgE antibodies in mice was
      investigated compared with aluminium-adsorbed tetanus toxoid (aTT) administered
      intranasally or subcutaneously. Mice immunized intranasally or subcutaneously
      with nTT together with rCTB showed a high level of TT-specific serum IgG antibody
      response and no or a slight level of TT-specific serum IgE antibody response. On
      the other hand, in mice vaccinated intranasally or subcutaneously with aTT alone,
      higher levels of TT-specific IgG and IgE antibodies were induced in comparison
      with intranasal or subcutaneous inoculation of nTT together with rCTB. These
      results suggest that intranasal or subcutaneous co-administration of rCTB with
      nTT is better than intranasal or subcutaneous administration of aTT to avoid IgE
      mediated allergic reactions.

PMID- 10067702
TI  - Diarrheagenicity evaluation of attenuated Vibrio cholerae O1 and O139 strains in
      the human intestine ex vivo.
AB  - The recent spread of El Tor cholera in Latin America highlights the need for a
      safe and economical vaccine. The main approach for developing live recombinant
      vaccines has been to disarm known pathogenic strains of cholera toxin leaving
      intact antigens involved in protection. These recombinant vaccine candidates do
      not cause severe diarrhea, but they are too reactogenic for wide scale usage. We
      describe here a test capable of determining the diarrheagenic potential of
      attenuated V. cholerae strains. The functional test consists in the simultaneous
      recording of net water movement, electrical potential difference and short
      circuit current across the human intestine ex vivo. We found that human tissues
      incubated with supernatants from the attenuated 638, 413 and 251a V. cholerae
      strains caused no changes in the ion conductances and water absorption in ileal
      and colon tissues allowing them to be assayed in volunteers.

PMID- 10067703
TI  - Vaccination of mice with a combination of BCG and killed Leishmania promastigotes
      reduces acute Trypanosoma cruzi infection by promoting an IFN-gamma response.
AB  - The combination of BCG with killed Leishmania promastigotes, demonstrated to be
      efficient in the cure of patients suffering American cutaneous leishmaniasis and
      in the induction of a long-term immune response in healthy vaccinated volunteers,
      was tested in BALB/c mice infected with Trypanosoma cruzi, in comparison to BCG
      or Leishmania alone, and a vehicle (PBS) control. BCG-Leishmania vaccination,
      applied intra-peritoneally 10 and 3 days before T. cruzi trypomastigote
      inoculation, prolonged the survival, and reduced blood parasitaemia of infected
      animals. Proliferation studies indicated that splenocytes of mice vaccinated with
      BCG-Leishmania and harvested in the acute phase of T. cruzi infection displayed
      stimulation indices higher than cells from PBS-treated mice when stimulated with
      PHA mitogen, PPD, Leishmania or T. cruzi antigens. Injections of a monoclonal
      antibody able to neutralise IFN-gamma into BCG-Leishmania vaccinated mice
      increased parasitaemia to levels similar to those of control animals (treated
      with PBS) and reversed the beneficial effect of vaccination on the proliferative
      response to T. cruzi antigen. These results show that vaccination of mice with
      BCG plus killed Leishmania promastigotes delayed acute T. cruzi infection,
      stimulated a T-cell response to T. cruzi antigen and promoted IFN-gamma
      production.

PMID- 10067704
TI  - DNA is as effective as protein at inducing antibody in fish.
AB  - Antiviral vaccines are needed for fish. 50 microg plasmid DNA in saline by the
      intramuscular route and 10 microg beta-gal protein in a commercial oil adjuvant
      by the peritoneal route induced serum antibody of the same titre and avidity in
      goldfish. The DNA expressed beta-gal under control of the immediate early
      promoter/enhancer gene of human cytomegalovirus. Commercial bacterin vaccines are
      administered to fish by the intraperitoneal route with oil and this route for DNA
      induced only 2-fold less antibody than DNA by the intramuscular route. Bacterin
      vaccines and antiviral plasmid DNA could therefore be co-injected into the
      peritoneum of fish in an oil adjuvant as a single dose.

PMID- 10067705
TI  - The predicted pattern of emergence of vaccine-resistant hepatitis B: a cause for
      concern?
AB  - We develop an epidemiological model of hepatitis B virus (HBV) in The Gambia in
      order to investigate the possible patterns of emergence of a vaccine-resistant
      strain. Under pessimistic assumptions (e.g., the current vaccine provides no
      cross-immunity against the variant) the model predicts the variant will not
      become dominant over the wild-type for at least 50 years. Therefore the current
      low prevalence of variant infections is not evidence for high cross-immunity of
      the vaccine or for low infectiousness of the variant, but may simply be a
      consequence of the epidemiology of HBV. The efficacy of the present vaccine
      against possible variants needs to be evaluated now to determine whether vaccine
      modifications are required. However, the model also suggests that serological
      surveillance may be unable to determine this efficacy for 40-50 years.

PMID- 10067707
TI  - TC-83 vaccine protects against airborne or subcutaneous challenge with
      heterologous mouse-virulent strains of Venezuelan equine encephalitis virus.
AB  - Vaccination with TC-83 virus produced solid protection against subcutaneous
      challenge with Venezuelan equine encephalitis (VEEV) viruses from homologous and
      heterologous serogroups, but breakthrough infection and disease occurred after
      airborne challenge. Breakthrough occurred more often with time after vaccination,
      and was more frequent with epizootic, homologous serogroup 1A/B viruses than with
      enzootic, heterologous serogroup viruses. A decrease in VEEV-specific IgA levels
      in the respiratory tract of vaccinated mice may explain the increased frequency
      of breakthrough with time after vaccination. However increased breakthrough with
      the highly virulent homologous serogroup 1A/B viruses (compared to less virulent
      viruses from heterologous serogroups) may be a consequence of their greater
      ability to invade the brain via the olfactory neuroepithelium and olfactory
      nerve.

PMID- 10067706
TI  - A study of human rabies immune globulin manufactured by the Thai Red Cross.
AB  - This is a prospective post marketing study of 4496 patients presenting with
      severe animal bites in a canine rabies endemic region. They received human rabies
      immune globulin manufactured from volunteer blood donors at the National Blood
      Center of the Thai Red Cross Society at Bangkok. All patients also received a
      full course of tissue culture rabies vaccine. Only three subjects reported an
      adverse reaction (redness and itching at the immune globulin injection sites).
      None of the patients died during the subsequent 18 month follow up period.

PMID- 10067708
TI  - Some important issues in the planning of phase III HIV vaccine efficacy trials.
AB  - Given that interesting HIV vaccine candidates, including live preparations and
      DNA plasmids, exist and that the first phase III vaccine (AIDSVAX) testing is due
      to begin this summer, 1998, in the U.S., adequately addressing trial preparedness
      is a pressing issue. Despite double-blind randomized controlled clinical trial
      design, there may be difficulties with interpretation and use of the usual
      measures of vaccinal efficacy and calculation of sample size. Difficulties arise
      from vaccine characteristics (e.g. mode of action, time-lag, waning) and
      population heterogeneities (e.g. differences in susceptibility, sexual behaviour,
      mixing preferences) causing frailty effects that can exacerbate bias and time
      dependent effects already known to exist in simple cases. Since vaccine
      properties, particularly mode of action, are unlikely to be known before the
      onset of clinical trials, choosing an efficacy measure and the associated
      analyses and sample size calculations will be problematic. Interim analyses
      designed to decide whether a study will be prolonged may be tenuous if based on a
      time-dependent measure and will influence sample size determination. Despite
      shortcomings, general recommendations can be made to minimise pernicious effects.
      The objectives of this paper are principally to review the current state of
      knowledge of the different stages in the preparation of large phase III HIV
      vaccine efficacy trials, the methodological difficulties related to their design,
      and the analysis of data collected from them. Mathematical models and trial
      simulations are used to demonstrate that further research is necessary to study
      the behaviour of vaccine efficacy measures under heterogeneous conditions of
      population, vaccine action, and trial design and identify a time-independent
      efficacy measure. Alternative methods to validate sample size calculations have
      to be developed in older to reduce the chances of unnecessary economic and human
      cost in phase III HIV vaccine trials.

PMID- 10067709
TI  - Heterotypic protection from rotavirus infection in mice vaccinated with virus
      like particles.
AB  - Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3
      serotype specificity were produced in insect cells coinfected with recombinant
      baculoviruses expressing single rotavirus genes. The VLPs were purified and
      subsequently evaluated for immunogenicity and protection in the adult mouse model
      of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs
      formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide
      (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions
      formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice
      were examined for serum and fecal antibody responses by ELISA or
      microneutralization assays. Protective efficacy of the VLP vaccine formulations
      against oral challenge with the G3 murine ECwt rotavirus was assessed by
      comparing the antigen shed in stool of the VLP-vaccinated mice to that of the
      adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and
      intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also
      heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented
      antibody responses were further characterized by equivalent IgG1 and IgG2a titers
      in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2
      response. G1 VLPs in QS-21 induced partial protection (88%) against oral
      challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced
      complete protection (100%). In contrast, G1 VLPs when formulated with AlOH
      induced a predominant Th2 response and did not protect (1%) mice from virus
      challenge. Our results indicate that the type of adjuvant used clearly influences
      both antibody responses to rotavirus VLPs and the protective efficacy against
      rotavirus infections. These data have important implications for the development
      of parenteral vaccines to ameliorate rotavirus disease.

PMID- 10067710
TI  - Between rubbish and the magnum opus.

PMID- 10067711
TI  - Repair of articular cartilage defects: part II. Treatment options.
AB  - Articular cartilage injuries result in numerous clinical symptoms, such as pain
      and decreased functional levels. Current therapeutic options being used include
      articular surface debridement, such as chondral shaving, abrasion chondroplasty,
      and subchondral perforation; soft-tissue arthroplasties, such as perichondrial
      and periosteal grafts; and osteochondral transplantation. None of these
      therapies, however, has resulted in the successful regeneration of a hyaline-like
      tissue that withstands normal joint loading and activity over prolonged periods.
      As a result, research is also being conducted on alternative therapeutic
      procedures to enhance the repair process and to stimulate the regeneration of a
      repair tissue with hyaline-like structural and biologic properties. Part I of
      this paper, which was published in January, discussed the basic science of
      cartilage healing. Part II presents the treatment options.

PMID- 10067712
TI  - Pain control and cultural norms and expectations after closed femoral shaft
      fractures.
AB  - The purpose of this observation-cohort survey study was to compare the analgesia
      given and satisfaction with analgesia after a uniform orthopedic injury and
      operation in culturally disparate settings. Twenty-five patients with isolated
      closed femoral shaft fractures treated with intramedullary rod fixation within 1
      week of injury were retrospectively evaluated at two urban hospitals in the
      United States. They were compared with a matched group from three urban hospitals
      in Vietnam (two in Hanoi and one in Ho Chi Minh City [Saigon]). Ages and sex did
      not differ significantly between the two groups. The mean weight of the
      Vietnamese group was significantly less than that of the US group (58 vs. 81 kg).
      During the 14 days following injury, the Vietnamese and American groups were
      given a mean of 0.9 mg/kg per day versus 30.2 mg/kg per day of morphine
      equivalent units, respectively. Two (8%) of the Vietnamese group felt their pain
      control had been inadequate, versus 20 (80%) of the US group. Similarly, 2 (8%)
      of the US group and 7 (28%) of the Vietnamese group felt they had received "too
      much" pain medication. Mean heart rates during the first 5 days after surgery
      were not significantly different in the two groups. Only 4% of the US group felt
      they had had an accurate impression of how much a femur fracture would hurt prior
      to the injury, whereas 76% of Vietnamese patients responded that they imagined
      such an injury would be approximately as painful as it was. Results were similar
      for preconceptions of pain as a result of surgery and during the postoperative
      period. More than 50% of patients from the US group felt there must be some
      explanation other than the femur fracture to explain the severity of their pain,
      such as infection, missed injury, hardware failure, or inappropriate medical
      care. Despite much higher administration of narcotic analgesia, American patients
      with femoral shaft fractures were much more dissatisfied with their analgesic
      results. In assessing the recommended dosing for "adequate analgesia" and
      "analgesic requirements," determinations may depend less upon tissue injury than
      upon cultural norms and patient expectations.

PMID- 10067713
TI  - The role of bilateral talectomy in the management of bilateral rigid clubfeet.
AB  - Severe clubfoot is a common sequela of arthrogryposis multiplex congenita and
      myelomeningocele. Talectomy is a practical surgical procedure to assist in the
      correction of severe, rigid equinovarus foot deformity. However, the results of
      talectomy may be less predictable in rigid bilateral equinovarus foot deformity
      than in the treatment of unilateral clubfoot. To determine the outcome of
      talectomy in the treatment of bilateral rigid clubfoot, we reviewed the cases of
      all patients at our center who underwent bilateral talectomy. Seven children were
      treated for bilateral talipes equinovarus with talectomy. The patient group
      consisted of 3 children with arthrogryposis, 3 with myelomeningocele, and 1 with
      Duchenne muscular dystrophy. The age at surgery averaged 6 years and ranged from
      1 year and 10 months to 15 years and 7 months. The length of follow-up averaged 5
      years and 6 months and ranged from 3 years to 12 years and 6 months. Three feet
      had a good and 7 feet a satisfactory correction of the deformity. Four feet had
      poor results. Bilateral talectomy was found overall to be a successful and
      predictable procedure, with low morbidity for the attainment of functional feet.

PMID- 10067714
TI  - Consequences of knuckle cracking: a report of two acute injuries.
AB  - A question commonly asked of physicians focuses on the possible deleterious
      effects of knuckle cracking. Patients are usually concerned that the risk of
      arthritis is increased by the habit; however, reports addressing the potential
      long-term consequence are controversial. We present two cases in which acute
      injuries were suffered while the patients were attempting to crack their
      knuckles. Both injuries responded well to conservative treatment. Our
      investigation shows that acute injuries can result from the forceful manipulation
      needed to achieve the audible pop of cracking knuckles and that patients should
      be counseled accordingly.

PMID- 10067715
TI  - Vertebra plana of the lumbar spine caused by an aneurysmal bone cyst: a case
      report.
AB  - The patient was a 15-year-old girl who had a lesion of the fourth lumbar
      vertebra. Plain radiographs suggested vertebra plana, with complete collapse of
      the body of the fourth lumbar vertebra and no involvement of the intervertebral
      disk spaces. The presumptive diagnosis was eosinophilic granuloma. Progressive
      neurologic symptoms required surgical excision of the lesion, decompression, and
      fusion. Histopathologic examination of the operative specimen confirmed the
      diagnosis of an aneurysmal bone cyst.

PMID- 10067716
TI  - Triplane fractures in the hand.
AB  - Two new cases of triplane fracture of the distal tibia are reported in the
      proximal phalanx of the thumb and the distal radius, respectively, of a 12-year
      old girl and a 13-year-old boy. Neither fracture showed any displacement,
      achieving healing at 4 weeks of external immobilization. Triplane fractures can
      occur across growth plates other than the distal tibia. Because of the rapid
      physiologic physeal arrest, the potential for growth deformity is null. In cases
      without displacement, these fractures should be treated conservatively by
      external immobilization, as one would treat a one-plane fracture.

PMID- 10067717
TI  - Retrospective report on the effectiveness of a polyurethane football helmet cover
      on the repeated occurrence of cerebral concussions.
AB  - This report reviews the literature and unpublished data and presents survey
      results related to the use of a polyurethane football helmet cover. Two hundred
      forty-five individuals, identified by the helmet manufacturer as having purchased
      at least one device, were sent a survey after the 1992, 1993, and 1994 football
      seasons; 155 (63.3%) of the surveys were returned. The questionnaire, designed to
      be completed by the athlete, required a detailed history of concussions occurring
      both prior to and during the period the device was used. Individuals used the
      device as a result of having incurred at least one concussion. Rates of
      concussion reoccurrence while the device was worn were grouped by the number of
      previous concussions (1, 2, 3, or 4+) that occurred over a 4year period prior to
      use of the device. The rate of concussion reoccurrence was 2.4%, 7.3%, 15.8%, and
      33.3%, respectively, over a 4-year period. The range appeared to reflect a
      parallel relationship between pre- and post-device concussion experiences: the
      more concussions experienced prior to adopting the device, the higher the rate of
      concussion reoccurrence while using the device. The natural history of repeated
      occurrences of concussive events may not be affected by the use of a polyurethane
      football helmet cover. We suggest that such a device not be routinely used
      prophylactically, but instead be reserved for individuals with 1 to 2 prior
      concussion injuries. However, at this time, we neither recommend nor discommend
      the device.

PMID- 10067718
TI  - The mechanism underlying aspirin's anti-inflammatory effects: a new twist to an
      old tale.

PMID- 10067719
TI  - How many wrongs make a right (or a left)? Vertebrate asymmetry unraveled.

PMID- 10067720
TI  - Helicobacter pylori infection in children--an update.

PMID- 10067721
TI  - Disaccharidase activities in children.

PMID- 10067722
TI  - Fish oil: for use in infant formula?

PMID- 10067723
TI  - Disaccharidase activities in children: normal values and comparison based on
      symptoms and histologic changes.
AB  - BACKGROUND: The relationship between symptoms, intestinal mucosal histology, and
      disaccharidase activities is not well defined. An analysis of disaccharidase
      activities was performed in children grouped by age, symptoms, and intestinal
      mucosal histology and normal values established. METHODS: Disaccharidase
      activities and histology of 246 endoscopically obtained duodenal biopsies in 232
      patients (121 girls; age range, 0.08-17 years; mean, 5.9 years) in a 3-year
      period were reviewed. Patients were divided into two groups based on absence
      (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided
      by age into, less than 24 months of age and 24 months of age or more. Histologic
      changes within groups were classified as (A) normal, (B) mild, or (C) moderate to
      severe based on villus height abnormalities. A questionnaire was sent to 34
      patients with hypolactasia to assess the efficacy of lactose avoidance and/or
      lactase supplementation. RESULTS: All group 1 patients had normal findings in
      analysis of mucosal specimens, and their disaccharidase activities showed normal
      values because they had no diarrhea. The geometric means (95% confidence
      interval) in children aged less than 24 months are (in micromoles of substrate
      hydrolyzed per minute at 37 degrees C per gram protein) (units [U]) lactase, 36.7
      (13.4-100.4); maltase, 178.5 (88.9-356.3); palatinase, 12.7 (3.8-41.5); and
      sucrase 60.0 (24.0-148.1). In children 24 months of age or more, the values are
      23.2 (3.9-108.1), 167.6 (78.8-355.9), 12.7 (4.9-32.9), and 51.0 (20.5-126.0),
      respectively. Only lactase activity decreased with age (p < 0.05). No differences
      in disaccharidase activities were noted in patients with and without diarrhea if
      the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea,
      values were commensurate with the degree of mucosal injury, especially in the
      older group. Twenty-two of 27 patients (81%) who responded to the questionnaire
      had benefited from lactase supplementation and/or lactose avoidance. CONCLUSIONS:
      We have established normal values for disaccharidase activities in the pediatric
      population. Although the disaccharidase activities correlate more with degree of
      intestinal mucosal injury than with symptoms, their activities are difficult to
      predict accurately based on these criteria. If required, disaccharidase
      activities should be measured biochemically.

PMID- 10067724
TI  - Reverse transcription-polymerase chain reaction in the diagnosis of Helicobacter
      pylori infection in Finnish children.
AB  - BACKGROUND: The purpose of this study was to design a simplified polymerase chain
      reaction (PCR) technique for the detection of Helicobacter pylori and to compare
      it with conventional diagnostic methods-culture and histology of gastric biopsy
      specimens. In addition, the capability of this technique to detect H. pylori in
      the gastric mucosal biopsies of originally H. pylori-negative children with
      gastritis or recurrent abdominal pain was investigated. METHODS: Reverse
      transcriptase polymerase chain reaction (RT-PCR) using polymerase from Thermus
      thermophilus was applied to detect H. pylori 16S rRNA. Twenty-five children H.
      pylori-positive by culture and/or histology were used as positive control
      subjects. Sixteen healthy H. pylori-negative children served as negative control
      subjects. Biopsy specimens from gastric antrum and corpus from 81 children were
      examined by RT-PCR. Altogether, 30 had histologic gastritis and 51 had
      nonspecific abdominal pain only, with no disease in histologic specimens.
      Histology and culture of H. pylori were negative in both patient groups. RESULTS:
      Reverse transcription-polymerase chain reaction detected 24 of 25 tissue-positive
      and 0 of 16 tissue-negative cases, indicating 96% sensitivity and 100%
      specificity for the test. None of the culturally and histologically H. pylori
      negative samples showed H. pylori colonization when analyzed by RT-PCR.
      CONCLUSIONS: RT-PCR using Thermus thermophilus polymerase is a fast and simple
      means of detecting H. pylori in gastric biopsy specimens. It is at least as
      specific and sensitive as conventional methods. In pediatric patients it may be
      necessary to take more than two biopsy specimens to increase sensitivity in cases
      of local or patchy colonization.

PMID- 10067725
TI  - S-fimbriae from Escherichia coli bind to soluble glycoproteins from human milk.
AB  - BACKGROUND: Escherichia coli (E. coli) strains, expressing S-fimbriae, belong to
      the most common gram-negative pathogens that cause sepsis and meningitis in
      neonates. The attachment of S-fimbriae to the cell surface is mediated by
      membrane glycoconjugates, which often carry N-acetylneuraminic acid. METHODS:
      Binding studies were performed with glycoproteins from the whey fraction of human
      milk to investigate whether they exert a potential inhibitory effect on bacterial
      adhesion. Whey glycoproteins were separated according to their molecular weight
      by fast protein liquid chromatography gel filtration. After sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, proteins were transferred to
      nitrocellulose membranes and incubated with isolated S-fimbriae from recombinant
      E. coli strain HB 101 (pANN 801-4). RESULTS: S-fimbriae recognized four whey
      proteins with a molecular mass of more than 200 kDa, 170 to 150 kDa, and 80 kDa.
      Their glycosylation pattern was investigated using the lectins Sambucus nigra,
      Maackia amurensis, Galanthus nivalis, and Arachis hypogaea. Thus the presence of
      N- and O-glycans in these proteins was confirmed. The preferential binding to N
      acetylneuraminic acid containing glycoproteins was demonstrated by a complete
      abolishment of these reactions by incubation with acidic lactose-derived
      oligosaccharides. However, the cleavage of N-acetylneuraminic acid from
      glycoproteins by mild acid hydrolysis revealed a second binding site for S
      fimbriae on milk proteins of a similar molecular weight range. Terminal galactose
      in human milk glycoconjugates were thought to react with S-fimbriae as well.
      CONCLUSION: These data further support the opinion that glycoproteins from human
      milk are potential receptor analogues for certain bacteria that may prevent
      microbial adhesion to the epithelial cell surface.

PMID- 10067726
TI  - Altered intestinal permeability to mannitol in diabetes mellitus type I.
AB  - BACKGROUND: Intestinal permeability has seldom been investigated in diabetes
      mellitus, even though patients frequently report gastrointestinal symptoms, and
      it has recently been shown that the prevalence of celiac disease associated with
      diabetes mellitus is higher than expected. METHODS: Intestinal permeability to
      cellobiose and mannitol was investigated in 31 patients affected by type I
      uncomplicated diabetes mellitus. Values were compared with those obtained in 32
      normal subjects. RESULTS: The percentage of mannitol recovery was far higher than
      normal in two thirds of the investigated patients and correlated with the length
      of disease, even though the probes' ratio (cellobiose/mannitol) was in the normal
      range. CONCLUSIONS: A not previously reported increase of intestinal permeability
      to mannitol, clear-cut and not associated with that of the larger probe, is found
      in type I uncomplicated diabetes mellitus. These results may describe a primary
      feature of type I diabetes mellitus and the initial steps of evolution to celiac
      disease.

PMID- 10067727
TI  - Aluminum contents of human milk, cow's milk, and infant formulas.
AB  - BACKGROUND: Aluminum toxicity is well documented and contamination of milk
      formulas has been implicated as the source of accumulation in bone and brain
      tissues. The purpose of the current study was to evaluate the aluminum contents
      of human milk, cow's milk, and infant formulas. METHODS: Aluminum contents were
      determined by atomic absorption spectrometry in samples of human milk in the
      colostrum, intermediate, and mature stages; infant formulas from eight
      manufacturers; and various types and brands of commercially available cow's milk.
      RESULTS: Mean aluminum concentration was lowest in human milk (23.4 +/- 9.6
      microg/l), and did not differ significantly between colostrum, intermediate-stage
      and mature-stage milk. Mean aluminum concentration was 70 microg/l in cow's milk,
      and 226 microg/l in reconstituted infant formulas. Aluminum concentrations in
      infant formulas differed markedly among manufacturers; concentration in milk from
      one of the manufacturers was particularly high (mean, 551 microg/l; range, 302
      1149 microg/l). These values are for milk reconstituted with aluminum-free water
      under laboratory conditions; formulas prepared with tap water in the University
      Hospital's infant-feeding unit had even higher aluminum content. Experiments
      showed that aluminum concentration in the high-aluminum milk could be reduced by
      more than 70% at the manufacturing stage, by using low aluminum components.
      CONCLUSIONS: The results of the present study support the recommendations for
      infant formula manufacturers to strive to reduce aluminum concentration in their
      products.

PMID- 10067728
TI  - Fish oil supplementation does not impair the gut immune response to Trichinella
      spiralis infection in rats.
AB  - BACKGROUND: Fish oil has been recommended as a source of omega-3 fatty acids for
      preterm infants and for therapy of some inflammatory diseases. METHODS: Because
      fish oil supplementation could downregulate the host's immune response, we
      studied the gut inflammatory response to an enteric infection in 72 rats assigned
      to three dietary groups with differing fatty acid profile: 1) fish oil, rich in
      eicosapentaenoic and docosahexaenoic acid; 2) olive oil, containing 71%
      monounsaturated fat; and 3) rat chow, containing 57% saturated fat. One half (n =
      36) of the rats were infected with Trichinella spiralis larvae; the other half
      served as controls. The inflammatory response to initial infection (study 1), and
      type I hypersensitivity response to a subsequent parasite-derived antigenic
      challenge (study 2) were assessed. Jejunal inflammatory cell infiltrate, mean
      villus height, disaccharidase levels, changes in short-circuit current in
      response to glucose absorption, and chloride secretagogues (study 1) were
      measured 9 days after infection. Short-circuit current changes induced by
      chloride secretion were measured when the proximal jejunum was challenged with T.
      spiralis-derived antigen 40 days after infection (study 2). RESULTS: In study 1,
      jejunal tissue from infected animals had more eosinophilic infiltrate, lower
      disaccharidase levels, and less glucose absorptive and chloride secretory
      capacity than tissue from noninfected animals. In study 2, the jejunum of
      infected animals showed an antigen-induced chloride secretory response, whereas
      no response was obtained from jejunal tissue from noninfected animals. Type of
      diet did not affect the response in either study. CONCLUSION: Under the
      conditions of this experiment, fish oil supplementation did not interfere with
      the local intestinal inflammatory response after T. spiralis infection.

PMID- 10067729
TI  - Epidemiology of altered intestinal permeability to lactulose and mannitol in
      Guatemalan infants.
AB  - BACKGROUND: Subclinical alterations of small intestinal function have been
      reported frequently in tropical countries. Studies of small intestinal
      permeability to lactulose and mannitol were therefore completed in Guatemalan
      infants from a low-income, periurban community to assess the prevalence of
      altered intestinal function and the factors associated with this condition.
      METHODS: Two hundred studies were successfully completed in 158 infants who had
      been free of diarrhea for at least 1 week before the day of study. Urinary
      concentrations of lactulose and mannitol during the 5-hour period after ingestion
      of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were
      measured by gas-liquid chromatography and compared by age group, feeding
      practices, anthropometric indexes, and serum iron and zinc concentrations.
      RESULTS: The overall prevalence of altered intestinal permeability (defined as a
      ratio of urinary recovery of lactulose to mannitol [L/M] > or =0.07) was 30%. The
      urinary L/M recovery ratio was positively associated with age; low weight for
      age; and, in infants less than 6 months of age, non-breast-feeding. Children with
      serum iron concentrations less than 7.16 microM/l (40 [microg/dl) had higher
      median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than
      those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p
      = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic
      infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154)
      was higher than that in children who had been free from diarrhea for at least 1
      week (0.052; CI = 0.048, 0.056; p = 0.01). CONCLUSION: Age, feeding practices,
      low weight-for-age, low serum iron concentration, and recent diarrhea were all
      associated with altered intestinal function in this group of Guatemalan infants.

PMID- 10067730
TI  - The effects of acetylsalicylic acid, interferon-alpha, and vitamin E on
      prevention of parenteral nutrition-associated cholestasis: an experimental study.
AB  - BACKGROUND: Cholestasis is one of the major complications of parenteral
      nutrition. The purpose of this experimental study was to detect the effects of
      acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon-alpha (IFN-alpha)
      on prevention of parenteral nutrition-associated cholestasis. METHODS: Ten
      experimental groups, each consisting of 10 4-week-old Wistar albino rats, were
      formed: control 10- and 20-day groups (C10 and C20), parenteral nutrition-only 10
      and 20-day groups (T10 and T20), ASA-supplemented parenteral nutrition 10- and
      20-day groups (TA10 and TA20), Vit E-supplemented parenteral nutrition 10- and 20
      day groups (TE10 and TE20), and IFN-alpha-supplemented 10- and 20-day groups
      (TF10 and TF20). Acetylsalicylic acid, Vit E, and IFN-alpha were administered in
      the parenteral nutrition solution through an intraperitoneal route. At the end of
      the study, serum total bile acids, serum aspartate and alanine aminotransferases,
      and alkaline phosphatase were measured biochemically. In addition, the
      histopathologic findings of cholestasis were evaluated by using a morphologic
      portal inflammation index. RESULTS: Although the difference in the serum levels
      of transferases and alkaline phosphatase was not significant among all groups (p
      > 0.05), it was significant in total bile acid levels (p < 0.05). There was also
      a significant correlation between the histopathologic changes of the liver and
      serum total bile acid concentrations (p < 0.05). Portal inflammation in varying
      degrees was seen in all experimental groups, but not in the control groups. Serum
      total bile acid concentrations in parenteral nutrition groups receiving ASA were
      significantly lower than those in the parenteral nutrition-only group (p < 0.01).
      Although Vit E-supplemented parenteral nutrition was effective in preventing the
      development of cholestasis in the 10-day group (p < 0.05), it was not effective
      in the 20-day group when compared with incidence of cholestasis in the parenteral
      nutrition-only group (p > 0.05). Conversely, IFN-alpha-supplemented parenteral
      nutrition had no effect on cholestasis in the 10-day group (p > 0.05) but lowered
      cholestasis in the 20-day group when compared with incidence the parenteral
      nutrition-only group (p < 0.05). CONCLUSION: Our results indicate that
      acetylsalicylic acid may be beneficial in preventing, and (alpha-interferon in
      treating, parenteral nutrition-associated cholestasis.

PMID- 10067731
TI  - Helicobacter pylori and nonulcer dyspepsia in childhood: clinical pattern,
      diagnostic techniques, and bacterial strains.
AB  - BACKGROUND: This is a report of the results of a multicenter study performed in
      children with dyspepsia from five pediatric centers in Puglia, a region in
      southern Italy. In the study, clinical features of Helicobacter pylori infection,
      the reliability of diagnostic techniques, and the involvement of bacterial
      strains were examined. METHODS: Fifty-three outpatients with dyspepsia enrolled
      in our study and compiled a diary recording clinical symptoms in patients before
      they underwent the following diagnostic techniques: endoscopy, biopsy for
      histologic analysis, rapid urease test, 13C urea breath test, serology specific
      for immunoglobulin (Ig)G and anti-CagA and VacA. RESULTS: H. pylori showed a
      prevalence of 30.2% (n = 16). Histologic positivity was seen in all patients at
      the antral level (H. pylori-associated chronic gastritis). In the gastric body,
      bacterial chronic active gastritis was present only in six patients (H. pylori
      associated chronic pangastritis). Clinical evaluation showed a significant
      difference in favor of subjects positive for H. pylori only for epigastric
      burning and/or pain (p < 0.001). The comparison of results of diagnostic tests,
      using histology as the gold standard, showed sensitivity and specificity of more
      than 93% for 13C urea breath test and more than 85% for rapid urease test and
      serology. Anti-CagA antibodies were found in 64.3% and anti-VacA antibodies in
      42.8% of H. pylori-positive patients. CONCLUSIONS: H. pylori prevalence in
      children with dyspepsia from the geographic area studied is comparable with that
      found in other developed countries. Approximately 50% of the studied patients
      were infected by cytotoxic strains. The urea breath test was the most reliable
      noninvasive diagnostic tool and is suitable for routine use, although endoscopy
      with histologic assessment remains the definitive investigation and is
      particularly important in patients with positive serology for CagA and VacA.
      Finally, the frequency of aggressive strains in our region seems to affect the
      clinical pattern; this emphasizes the importance of definitive diagnosis in
      children and offers a new role for serology.

PMID- 10067732
TI  - Prevalence of Helicobacter pylori infection detected by serology and 13C-urea
      breath test in HIV-1 perinatally infected children.
AB  - BACKGROUND: Conflicting results have been reported in adults with human
      immunodeficiency virus (HIV-1) who were investigated for Helicobacter pylori
      infection. Most studies indicate a lower prevalence than is found in the general
      population. The purposes of this study were to evaluate H. pylori prevalence by
      noninvasive methods in a population of children perinatally infected with HIV-1
      and to correlate H. pylori prevalence with HIV-1-related clinical and immunologic
      status. METHODS: H. pylori infection was studied in 45 children perinatally
      infected with HIV-1 by performing serologic testing of anti-H. pylori
      immunoglobulin G antibodies and the 13C-urea breath test. RESULTS: Eight children
      with HIV-1 (17.7%) were positive by serology, and nine (20%) were positive by 13C
      urea breath test. No significant differences related to age, previous antibiotic
      treatment, immunoglobulin administration, antiretroviral treatment, abdominal
      pain, CD4+ cell count, number of HIV-1 RNA copies, and frequency of severe
      immunodepression were noted between children with positive 13C-urea breath test
      results and those with negative results. Children with positive results were
      significantly more likely to have severe clinical manifestations. CONCLUSIONS:
      The results show, by both serology and 13C-urea breath test, a prevalence of H.
      pylori infection comparable with the prevalence in the normal population of the
      same age. H. pylori prevalence has probably been underestimated in patients with
      HIV. Results of serologic and histologic analyses for H. pylori require cautious
      interpretation, especially in severely immunodeficient patients.

PMID- 10067733
TI  - Helicobacter pylori and type 1 diabetes mellitus in children.
AB  - BACKGROUND: Helicobacter pylori is a recognized gastroduodenal pathogen and H.
      pylori infection is one of the most common bacterial infections, usually acquired
      during childhood. However, diabetes mellitus is characterized by an increased
      susceptibility to infections. METHODS: We compared the prevalence of H. pylori
      infection as well as cytotoxin-associated gene A-CagA-and vacuolating cytotoxin
      gene A-VacA-positivity in 103 children and adolescents with type 1 diabetes
      mellitus and in 236 nondiabetic children. We used a novel Recombinant ImmunoBlot
      Assay-Strip (RIBA SIA) with individual band for whole H. pylori lysate and
      recombinant CagA and VacA. RESULTS: H. pylori-positive subjects, both diabetics
      and controls, were significantly older than negative subjects. In the whole group
      of diabetic patients the prevalence of each of the three reactivities was higher
      than in control subjects, reaching significance only for lysate. Only diabetic
      patients over 12 years of age, with a longer disease duration, had a higher
      prevalence of positive cases, although not significantly so. CONCLUSIONS: In the
      first few years of disease, diabetic children do not differ from the nondiabetic
      population. Subsequently they show an H. pylori seroprevalence tendentially
      higher than that of controls of the same age. Therefore, H. pylori infection
      acquired in childhood and lasting several years, could be one of the causes of
      chronic atrophic gastritis, which is more frequent in longstanding diabetes
      mellitus.

PMID- 10067734
TI  - Nitrous oxide sedation in pediatric patients undergoing gastrointestinal
      endoscopy.
AB  - BACKGROUND: The ideal medication to administer to children before
      gastrointestinal endoscopy procedures has yet to be found. The efficacy of using
      inhaled nitrous oxide during endoscopy in children was assessed in a pilot study.
      METHODS: Patients aged 5 to 17 years, referred to our hospital for diagnostic
      upper gastrointestinal endoscopy or rectosigmoidoscopy procedures, were eligible
      for enrollment in this study. All received 50% nitrous oxide in oxygen (Entonox;
      AGA, Rueil-Malmaison, France) before endoscopy and some of them again during
      endoscopy. The pediatric endoscopist and the nurse performing the procedure were
      separately asked to rate cooperation, emotional state, drowsiness and overall
      efficacy of sedation. Oxygen saturation and adverse effects were recorded
      throughout the procedure. After endoscopy, children scored their degree of pain
      during the procedures on a visual analog scale (0, no pain; 100, agony) and on a
      body outline (projective method). Any adverse effects were noted. RESULTS: Thirty
      seven patients were enrolled in the study. Thirty patients underwent diagnostic
      upper gastrointestinal endoscopy and seven diagnostic rectosigmoidoscopy. The
      median time from administration of nitrous oxide until insertion of the endoscope
      was 5 minutes (range, 3-8 minutes). Good or excellent efficacy of the sedation
      was noted in 92% of children by the endoscopist and in 89% by the nurses. Good or
      excellent cooperation was noted in 92% of the children by the endoscopist and in
      78% by the nurses. The children's pain score on the visual analog scale ranged
      from 5 to 100 (median, 20) for upper gastrointestinal endoscopy and from 0 to 30
      (median, 0) for rectosigmoidoscopy. The time of discharge after endoscopy,
      defined as the time elapsed between the end of the endoscopy and discharge from
      the endoscopy suite, varied from 1 to 7 minutes (median, 1.5 minutes).
      CONCLUSION: Entonox provides rapid and effective analgesia without heavy
      sedation, leads to adequate relaxation and cooperation, and facilitates quick and
      efficient endoscopy. The effect of Entonox was of short duration, allowing the
      children to leave the endoscopy unit without need for a long recovery period. The
      adverse effects of Entonox appeared to be minor, and their duration was always
      brief. Nitrous oxide-oxygen inhalation may provide a valuable alternative to
      conventional sedation regimens during gastrointestinal endoscopy in children, but
      randomized and prospective studies comparing nitrous oxide sedation and
      conventional sedation regimens are necessary.

PMID- 10067735
TI  - Growth hormone stimulates, through tyrosine kinase, ion transport and
      proliferation in human intestinal cells.
AB  - BACKGROUND: Growth hormone (GH) stimulates intestinal growth and differentiation
      and promotes water and ion absorption in the rat intestine. Epidermal growth
      factor has similar effects, which involve tyrosine kinase activity. The effects
      of growth hormone on ion transport and cell growth and the role of tyrosine
      kinase in these effects were examined in a human-derived intestinal cell line
      (Caco-2). METHODS: For transport study, electrical parameters were measured in
      human intestinal Caco-2 cell monolayers mounted in Ussing chambers. Cell growth
      was monitored by counting and 3H-thymidine incorporation in the presence and
      absence of growth hormone. The role of tyrosine kinase was investigated by using
      its specific inhibitor genistein. RESULTS: The addition of growth hormone induced
      a rapid, Cl- -dependent, decrease in short-circuit current without affecting
      tissue conductance, which is consistent with an anion-absorptive effect.
      Incubation with growth hormone increased cell count by 85% and 3H-thymidine
      incorporation by 64% versus the count in control specimens. The absorptive and
      trophic effects of growth hormone were dose-dependent, and the maximum effective
      concentration was identical for each effect. Genistein blocked the growth hormone
      effect on ion transport and cell growth. CONCLUSIONS: Growth hormone stimulates
      ion absorption and cell growth in human enterocytes. Both effects result from a
      direct growth hormone-enterocyte interaction, and both require tyrosine kinase
      activity. Growth hormone may have therapeutic potential in intestinal diseases
      characterized by epithelial atrophy and loss of water and electrolytes.

PMID- 10067736
TI  - Clinical quiz. Histoplasma capsulatum.

PMID- 10067737
TI  - Metastatic Crohn's disease in a 9-year-old boy.

PMID- 10067738
TI  - Unexplained chronic bronchial suppuration and inflammatory bowel disease.

PMID- 10067739
TI  - Rectal cancer in an 11-year-old girl with hyperplastic polyposis.

PMID- 10067740
TI  - Cyclosporine for rectoperineal fistula in a human immunodeficiency virus-infected
      child.

PMID- 10067741
TI  - Meckel's diverticulitis associated with Schistosoma mansoni.

PMID- 10067742
TI  - Hepatic capillariasis in a 2-year-old boy.

PMID- 10067743
TI  - Treatment of Helicobacter heilmannii-associated gastritis in a 14-year-old boy.

PMID- 10067744
TI  - Congenital microgastria: treatment with transient jejunal feedings.

PMID- 10067745
TI  - Meckel's diverticulum as a rare cause of chronic screaming: the importance of
      clinical examination during anaesthesia.

PMID- 10067746
TI  - Progress in the prevention and treatment of osteoporosis in pediatrics.

PMID- 10067747
TI  - An explanation for growth impairment in chronic inflammation.

PMID- 10067748
TI  - Inflammatory bowel disease, autism, and the measles, mumps, and rubella vaccine.

PMID- 10067749
TI  - Comparison of fiberendoscopy and suction capsule for small intestinal biopsy in
      children with and without celiac disease.

PMID- 10067750
TI  - Celiac disease and selective IgA deficiency in a girl with atypical Turner
      syndrome.

PMID- 10067751
TI  - The rate of Helicobacter pylori infection in children with growth retardation.

PMID- 10067752
TI  - Food allergy and tacrolimus.

PMID- 10067753
TI  - Managing intrafamilial dissemination of Helicobacter pylori gastric infection
      improves eradication rate in children.

PMID- 10067754
TI  - The technological imperative in craniofacial surgery.

PMID- 10067755
TI  - Psychological issues in craniofacial care: state of the art.
AB  - This article is an extensive review of the psychological literature on cleft lip
      and palate and other craniofacial anomalies. Issues of parental acceptance,
      social competence, self-concept, emotional adjustment, and cognitive functioning
      are examined. Cumulative research suggests that many children with craniofacial
      conditions develop in a typical manner and do not experience psychological
      problems. However, a significant number of children (30% to 40% in most studies)
      experience difficulties with internalizing and/or externalizing problems,
      learning disorders, and social competence. A multifactorial model for examining
      the domains that are related to both psychological risk and protection is
      recommended. The need for multicenter studies that are prospective and clinically
      relevant is emphasized.

PMID- 10067757
TI  - Dr. Roux's first operation of soft palate in 1819: a historical vignette.

PMID- 10067756
TI  - Progress toward understanding craniofacial malformations.
AB  - Significant advances in the study of the human face have revealed the genetic and
      gene-environment bases of numerous common and rare craniofacial disorders.
      Classification of craniofacial malformations based on clinical phenotypes is
      sometimes quite different from the genetic findings of patients. Different
      mutations in a single gene can cause distinct syndromes, and mutations in
      different genes can cause the same syndrome. The extracellular signaling molecule
      SHH, fibroblast growth factor receptors, and transcription factors GLI3, MSX2,
      and TWIST are discussed as examples of molecules involved in interrelated signal
      transduction networks regulating craniofacial development. Progress in the
      understanding of normal and abnormal craniofacial development, through the study
      of morphoregulatory signaling pathways, has benefited from multifactorial
      approaches recommended 40 years ago at the National Institute of Dental Research
      sponsored landmark Gatlinburg Conference. The utilization of biochemistry,
      protein structure analyses, tissue culture, and animal model systems for
      developmental genetics has resulted in remarkable scientific advances. The
      evolutionary conservation of morphoregulatory pathways has revealed the homology
      of genes associated with human craniofacial malformations and their counterparts
      that regulate the morphogenesis of fruit flies. The continued investments in
      basic, translational, and patient-oriented research regarding normal and abnormal
      craniofacial development will translate into substantial improvements in the
      prevention, diagnosis, and treatment of craniofacial diseases and disorders.

PMID- 10067758
TI  - Medical genetics on the cleft palate-craniofacial team: understanding parental
      preference.
AB  - OBJECTIVE: This study examined health care professionals' perceptions of parental
      preferences and preferences of parents of affected children (cleft lip, cleft
      palate, both, or other craniofacial anomaly) for prenatal testing with respect to
      oral-facial clefts and craniofacial anomalies. DESIGN: This was a descriptive
      study assessing and comparing questionnaire responses of two independent groups.
      PARTICIPANTS: Healthcare professional participants comprised 570 U.S. members of
      the American Cleft Palate-Craniofacial Association. Parent participants comprised
      97 parents of children seen at the University of Pittsburgh Cleft Palate
      Craniofacial Center. MAIN OUTCOME MEASURES: A practitioner survey was developed
      to examine practitioner perception of parental desire for involvement, desire for
      knowledge, and reaction to learning of a birth defect. A parent survey was
      developed to correspond with the practitioner survey. RESULTS: Health
      professionals' perceptions of parental preferences often paralleled parental
      preference data. However, parental responses were found to be significantly
      different from practitioner perception of parental preferences on one question
      reflecting desire for involvement (chi2 = 33.35, df=1, p = .001) and on one
      question reflecting desire for knowledge (chi2 = 4.82, df = 1, p = .03). For both
      questions, higher percentages of parents responded that they would want this
      involvement or information. CONCLUSIONS: Findings are consistent with those
      reported in other studies of prenatal testing preferences and susceptibility.
      Results suggest that parents of affected children have a strong desire for
      information and involvement in prenatal testing and counseling decisions. Parents
      appear to value preparation in spite of acknowledging anxiety associated with
      prenatal information.

PMID- 10067759
TI  - Points of risk and opportunity for parents of children with craniofacial
      conditions.

PMID- 10067760
TI  - Living with craniofacial microsomia: support for the patient and family.

PMID- 10067761
TI  - Psychosocial adjustment in twin pairs with and without hemifacial microsomia.
AB  - OBJECTIVE: To compare the psychosocial adjustment of children with and without
      hemifacial microsomia (HFM). DESIGN: This cross-sectional pilot study
      investigated psychosocial adjustment of twin pairs in which one twin was affected
      with HFM and the other was unimpaired. Data were analyzed using paired t tests.
      SETTING: The dental medicine clinic of a large urban children's hospital, serving
      a multistate area. PARTICIPANTS: Participants were six twin pairs aged 9 to 15
      years and their parents. Data were also collected from classroom teachers. MAIN
      OUTCOME MEASURES: Outcome measures included: the Child Behavior Checklist (CBCL),
      the Teacher Report Form (TRF), the Coopersmith Self-Esteem Inventory (SEI), and a
      structured self-concept interview (the Self-Interview). RESULTS: Children with
      HFM had significantly higher CBCL and TRF total behavior problem scores and lower
      SEI general self-esteem scores than their unimpaired twins. No differences were
      found in CBCL competence scores. Interview data revealed concerns among the HFM
      group related to appearance, negative social responses, and fear of hospital
      procedures. Children also reported positive aspects of coping with HFM.
      CONCLUSIONS: The results of this study suggest that, similar to other
      craniofacial conditions, HFM is associated with an elevated risk for childhood
      psychosocial difficulties. Replication of specific findings with a larger sample
      is needed. Multicenter, collaborative studies are a crucial next step for this
      field.

PMID- 10067762
TI  - The influence of dentures on nasalance values in speech.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of maxillary
      dentures on nasalance values in normal elderly individuals. DESIGN: A three
      factor within-subjects experimental design was employed to analyze the nasalance
      scores obtained. PARTICIPANTS: Twenty English-speaking women aged 61 to 81 years,
      who wore complete maxillary dentures, participated in the study. INTERVENTION: A
      Nasometer was used to collect nasalance data. Participants read three standard
      passages aloud, three times each, in two conditions: with and without their
      maxillary dentures. RESULTS: Results revealed that nasalance values were
      significantly lower with the maxillary dentures removed (p<.01), although the
      difference in nasalance between the two denture conditions averaged no more than
      2%. Nasalance scores obtained both with and without maxillary dentures fell
      within one standard deviation of the mean for a reference group of comparably
      aged English-speaking women. CONCLUSIONS: The results suggest that the existing
      collection of normal reference data for nasalance may be safely used for elderly
      individuals regardless of their status with respect to natural or prosthetic
      maxillary dentition.

PMID- 10067763
TI  - Nasalance statistics for two Mexican populations.
AB  - OBJECTIVES: This study was undertaken (1) to obtain nasalance statistics for 152
      Spanish-speaking normal males and females in three age groups (young children,
      older children, and adults) from two cities in central Mexico, (2) to determine
      the reliability of nasalance statistics, and (3) to test whether cities, age
      group, and/or gender significantly affected nasalance scores.
      DESIGN/PARTICIPANTS: Randomly selected volunteers, screened for normal speech and
      hearing, in two middle-class neighborhoods in each city participated. SETTINGS:
      Measures were made in private homes. MEASURES: Eight nasalance measures were
      obtained: means, "deviations," maxima, and minima for two sets of sentences; one
      set that contained no nasals (NN); and another set that included sentences
      containing several words with nasal sounds (N). RESULTS: Reliability (Cronbach's
      alpha) of the measures was demonstrated to be very high (0.87 to 0.95). Eight
      multivariate analyses of variance, one for each type of measure, were performed.
      Significant differences among subgroups were limited to four: (1) cities differed
      in their NN means, (2) age groups differed in their NN minima, (3) cities
      differed in their N minima, and (4) genders differed in their N minima.
      (Bonferroni adjusted alphas = 0.05).

PMID- 10067764
TI  - A teaching device for Furlow palatoplasty.
AB  - The Furlow double-opposing z-plasty technique of palate repair has become a
      common treatment for cleft palate. The procedure is more complicated than other
      methods of palate closure and is difficult for the trainee to visualize; It is
      even more difficult for the layperson without prior understanding of the concept
      of z-plasty to understand. A simple, inexpensive, portable model is described
      that shows the key elements of the repair and can be used for parent, patient,
      student, and resident teaching.

PMID- 10067765
TI  - Bone grafting of cleft lip and palate patients for placement of endosseous
      implants.
AB  - OBJECTIVE: Fixation of a prosthesis or single tooth replacement using
      osseointegrated implants has the potential to overcome functional and
      psychological inconveniences that many patients experience from such appliances.
      However, the dimensions of the recipient site are relatively often inadequate for
      implant placement. This study assessed grafting of this site with autogenous bone
      as a solution for the latter problem. METHODS: Ten cleft lip and palate patients
      had bone grafts; six had iliac crest grafts to the maxillary sinus floor (31
      implants), and four had chin bone grafts to the local defect in the anterior
      maxilla (six implants). Implants were inserted during the grafting procedure (one
      patient) or after 3 months (nine patients). RESULTS: No inflammation of the bone
      grafts or the maxillary sinus occurred. One implant was lost during the healing
      phase. Four single tooth restorations, one fixed bridge, and five implant
      supported overdentures were made. During the follow-up, which was 47 months
      (range, 28 to 65 months) in the anterior maxilla group and 56 months (range, 28
      to 68 months) in the posterior maxilla group, no loss of implants was observed,
      and all prosthetic appliances functioned well. CONCLUSIONS: It is concluded that
      bone grafting followed by placement of dental implants can serve as a reliable
      alternative for conventional prosthetic rehabilitation of cleft patients.

PMID- 10067766
TI  - Long-term outcome analysis of two treatment methods for cleft palate: combined
      levator retropositioning and pharyngeal flap versus double-opposing Z-plasty.
AB  - OBJECTIVE: Two surgical techniques for repair of a cleft palate include levator
      retropositioning in combination with a pharyngeal flap and the Furlow double
      opposing Z-plasty. This study compared morbidity and speech results from the use
      of these two methods in an effort to determine which was the superior technique.
      DESIGN: Patient records from 1986 to 1996 were retrospectively reviewed, and 10
      patients with a cleft palate who underwent repair with a levator retropositioning
      and pharyngeal flap were compared to 14 patients who underwent a double-opposing
      Z-plasty repair. Postoperative complications including fistula formation,
      obstructive sleep apnea, and residual velopharyngeal insufficiency were recorded.
      Speech was assessed perceptually and through the use of nasometry. RESULTS: Both
      surgical techniques resulted in good speech in the majority of patients. Only two
      patients in the study, both in the Z-plasty group, had severe postoperative
      hypernasality. Two patients in the levator retropositioning and pharyngeal flap
      group developed severe postoperative obstructive sleep apnea, requiring
      additional surgery. CONCLUSION: The levator retropositioning and pharyngeal flap
      technique was successful in achieving good speech results, but it also caused
      more serious postoperative complications when compared to the double-opposing Z
      plasty technique.

PMID- 10067767
TI  - Congenital fistulae of the lower lip in Van der Woude syndrome: a
      histomorphological study.
AB  - OBJECTIVE: To evaluate a significant number of cases of fistulae of the lower lip
      with the light microscope in order to investigate the histological variation and
      to attempt to define the histopathological pattern of the lesion. METHODS:
      Congenital fistulae of the lower lips of 17 patients with Van der Woude syndrome
      were analyzed by light microscopy. RESULTS AND CONCLUSION: The walls of most of
      the fistulae consisted of stratified nonkeratinized squamous epithelium and a
      lamina propria of dense connective tissue with areas of lymphohistiocytic
      inflammatory infiltrates. Bundles of striated muscle fibers, blood vessels,
      nerves, adipose tissue, and mixed acinar glands were observed. These glands
      surrounded the entire wall of the lesion, and their excretory ducts opened into
      the lumen of the fistula, explaining the clinical observation of elimination of
      mucous secretion through the opening of the fistula. Two microform cases of
      fistula were analyzed that presented only a depression in the epithelium at the
      site corresponding to the opening of the fistula.

PMID- 10067768
TI  - Median cleft of the lower lip associated with lip pits and cleft of the lip and
      palate.

PMID- 10067769
TI  - Learning disability, school achievement, and grade retention among children with
      cleft: a two-center study.

PMID- 10067770
TI  - Visual confrontation naming following left anterior temporal lobectomy: a
      comparison of surgical approaches.
AB  - Change in visual confrontation naming was examined following left (speech
      dominant) anterior temporal lobectomy (ATL) as a function of surgical technique
      and patient characteristics. Two hundred seventeen patients with intractable left
      temporal lobe epilepsy were selected according to standard criteria across 8
      centers, and combined into 4 surgical approaches to ATL: (a) tailored resections
      with intraoperative mapping of eloquent cortex, (b) tailored resections with
      extraoperative mapping, (c) standard resections with sparing of superior temporal
      gyrus, and (d) standard resections including excision of superior temporal gyrus.
      Changes in visual confrontation naming were examined with an index of reliable
      change derived from an independent sample of 90 nonsurgical patients with complex
      partial seizures. Results showed significant decline in visual confrontation
      naming following left ATL, regardless of surgical technique. Across surgical
      approaches, the risk for decline in visual confrontation naming was associated
      with a later age of seizure onset and more extensive resection of lateral
      temporal neocortex.

PMID- 10067771
TI  - Effects of divided attention on temporal processing in patients with lesions of
      the cerebellum or frontal lobe.
AB  - Prefrontal cortex and cerebellum have both been implicated in temporal processing
      tasks although the exact contribution of each system remains unclear. To
      investigate this issue, control participants and patients with either prefrontal
      or cerebellar lesions were tested on temporal and nontemporal perceptual tasks
      under 2 levels of attentional load. Each trial involved a comparison between a
      standard tone and a subsequent comparison tone that varied in frequency,
      duration, or both. When participants had to make concurrent judgments on both
      dimensions, patients with frontal lobe lesions were significantly impaired on
      both tasks whereas the variability of cerebellar patients increased in the
      duration task only. This dissociation suggests that deficits on temporal
      processing tasks observed in frontal patients can be related to the attention
      demands of such tasks; cerebellar patients have a more specific problem related
      to timing.

PMID- 10067772
TI  - Word-stem completion priming in healthy aging and Alzheimer's disease: the
      effects of age, cognitive status, and encoding.
AB  - There are many conflicting results concerning the effects of age and Alzheimer's
      disease (AD) on word-stem completion priming. To examine potential sources of
      this variability, the authors examined the influences on such priming of age,
      cognitive status, and encoding in a large sample of young, old, and AD
      individuals. At study, words were processed aloud by reading, reading and rating
      likeability, or generating from definition. Old participants had less priming
      than young participants and more priming than AD patients. For the healthy old
      participants, priming decreased with advancing age and with cognitive loss
      following generation only. For AD patients, priming decreased as dementia
      severity increased; patients with the mildest dementia did not differ from
      healthy old participants. Thus, age, cognitive status, and encoding
      differentially influenced the magnitude of priming in healthy aging and AD.

PMID- 10067773
TI  - The differentiation of semantic dementia and frontal lobe dementia (temporal and
      frontal variants of frontotemporal dementia) from early Alzheimer's disease: a
      comparative neuropsychological study.
AB  - The authors compared age-matched groups of patients with the frontal and temporal
      lobe variants of frontotemporal dementia (FTD; dementia of frontal type [DFT] and
      semantic dementia), early Alzheimer's disease (AD), and normal controls (n = 9
      per group) on a comprehensive neuropsychological battery. A distinct profile
      emerged for each group: Those with AD showed a severe deficit in episodic memory
      with more subtle, but significant, impairments in semantic memory and
      visuospatial skills; patients with semantic dementia showed the previously
      documented picture of isolated, but profound, semantic memory breakdown with
      anomia and surface dyslexia but were indistinguishable from the AD group on a
      test of story recall; and the DFT group were the least impaired and showed mild
      deficits in episodic memory and verbal fluency but normal semantic memory. The
      frontal and temporal presentations of FTD are clearly separable from each other
      and from early AD.

PMID- 10067774
TI  - The mere exposure effect in patients with Alzheimer's disease.
AB  - The mere exposure effect was examined in patients with mild to moderate
      Alzheimer's disease (AD). Twenty patients and 20 elderly controls judged the
      physical characteristics of faces. Implicit memory was tested later by presenting
      pairs of faces (old and new) and asking participants which faces they liked
      better. Patients and controls exhibited above chance preference for previously
      exposed faces. Experiment 2 evaluated whether the preserved implicit memory of
      patients was mediated by explicit memory. Patients and controls again judged
      faces but then later chose which faces they had seen before. Patients exhibited
      impaired recognition memory compared to controls. These findings suggest that a
      mere exposure effect for unfamiliar faces is present in mild to moderate AD. The
      results are discussed in terms of perceptual and conceptual priming and
      relatively spared occipital lobe functioning in early AD.

PMID- 10067775
TI  - Odor identification in normal aging and early Alzheimer's disease: effects of
      retrieval support.
AB  - Odor sensitivity and identification were examined in normal aging and early
      Alzheimer's disease (AD). The aims were to investigate AD as associated with
      lower odor sensitivity, odor identification as a function of retrieval support,
      and the relationship between global cognitive functioning (Mini-Mental State Exam
      [MMSE]; M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975) and olfactory
      performance. Results indicated intact odor sensitivity but deficient odor
      identification in AD. Both groups benefited from cues in identification, and the
      size of the gains was equally large in AD patients and controls. The finding of
      no selective benefit from retrieval support in AD suggests that a degradation of
      olfactory knowledge contributes to the odor identification deficits in these
      patients. MMSE and identification were positively related, whereas MMSE and
      olfactory sensitivity were unrelated. These findings suggest that the AD-related
      olfactory impairment stems from lesions in cortical rather than peripheral
      structures.

PMID- 10067776
TI  - Impairment of consciously controlled use of memory in schizophrenia.
AB  - Recent studies of memory in schizophrenia have shown that explicit but not
      implicit memory performance is impaired. The hypothesis that schizophrenia is
      associated with a failure of consciously but not unconsciously (automatic)
      controlled influence of memory on performance was tested using a procedure
      providing uncontaminated estimates of consciously controlled and automatic memory
      processes (i.e., the process-dissociation procedure in a stem completion task).
      Performance of 35 patients with schizophrenia was compared with that of 35 normal
      participants. Consciously controlled use but not automatic influences of memory
      was significantly lower in patients with schizophrenia than in controls.
      Consciously controlled use of memory was negatively and significantly correlated
      with positive symptoms of schizophrenia. Schizophrenia differentially affects 2
      types of memory processes: It impairs consciously controlled use of memory but
      spares automatic influences. Positive symptoms could reflect the lack of control
      from higher level conscious processes.

PMID- 10067777
TI  - Neurocognitive dysfunction in patients diagnosed with schizophrenia and
      alcoholism.
AB  - The authors administered the Halstead-Reitan Neuropsychological Test Battery to
      schizophrenic groups with (n = 54) and without (n = 217) coexisting alcoholism,
      nonschizophrenic groups with alcoholism (n = 231), and a patient comparison group
      (n = 145) to determine the extent of additive cognitive impairment in
      schizophrenia associated with alcoholism and to compare cognitive function in
      alcoholism and schizophrenia. The additive effects of alcoholism on cognitive
      dysfunction in schizophrenia were subtle but were consistently identifiable.
      Cognitive dysfunction in alcoholism was less severe than in schizophrenia with or
      without alcoholism. The magnitude of additive effects of alcoholism on cognitive
      dysfunction in schizophrenia was age related with a significant interaction
      between age and presence or absence of alcoholism on a global index of cognitive
      dysfunction.

PMID- 10067778
TI  - Neuropsychological deficits in psychotic versus nonpsychotic unipolar depression.
AB  - A broad range of neuropsychological function was compared in samples of young
      adult unipolar depressed inpatients with and without psychotic features.
      Consistent with expectations, the psychotic depressive group demonstrated a broad
      range of deficit and had more impaired performances than the nonpsychotic group.
      Relevance of these data for hypotheses concerning psychotic depression as a
      unique diagnostic entity is discussed. In the context of previous research, the
      current findings suggest that accounting for individual differences in depression
      may clarify discrepancies between earlier studies of neuropsychological function
      in depression, and our understanding of the mechanisms by which depression
      influences cognition may be refined.

PMID- 10067779
TI  - Influences on first-year recovery from traumatic brain injury in children.
AB  - This study examined recovery over the first year following traumatic brain injury
      (TBI) in children 6-12 years of age. Forty-two children with severe TBI and 52
      with moderate TBI were compared to 58 children with orthopedic injuries. The
      children and their families were evaluated at a baseline assessment and at 6- and
      12-month follow-ups. Findings documented cognitive, achievement, and behavioral
      sequelae of TBI, with only limited evidence for recovery over the first year
      postinjury. Outcomes were predicted by preinjury factors, TBI severity, and
      measures of the postinjury family environment. Some of the sequelae of severe TBI
      were more marked in the context of higher compared with lower levels of family
      burden or dysfunction. The findings confirm the need to consider environmental
      contributions to outcomes of TBI in children.

PMID- 10067780
TI  - Relationships among age, conditioned stimulus-unconditioned stimulus interval,
      and neuropsychological test performance.
AB  - To evaluate the effect of age at various conditioned stimulus (CS)-unconditioned
      stimulus (US) intervals, 144 young, middle-aged, and older adults were tested on
      eyeblink classical conditioning at CS-US intervals of 500, 1,000, or 1,500 ms.
      Reaction time, response timing, motor learning, declarative memory, and attention
      were assessed to identify correlates of conditioning at various CS-US intervals.
      Previously reported middle-aged and older adults were impaired at a 400-ms CS-US
      interval, but the addition of 100 ms to the CS-US interval in this study enabled
      equal conditioning in middle-aged and young adults. At a 1,000-ms CS-US interval,
      older adults remained significantly impaired. It was only at the 1,500-ms CS-US
      interval that conditioning was equal for the 3 age groups. Measures of reaction
      time, timing, and motor learning were not correlated systematically with
      conditioning. Whereas the results of age differences at various CS-US intervals
      were clear and striking, patterns of relationships among neuropsychological and
      conditioning variables were not consistent in indicating sources of age
      differences.

PMID- 10067781
TI  - Prospective memory: a neuropsychological study.
AB  - To examine the neuropsychology of prospective remembering, older adults were
      divided preexperimentally into 4 groups on the basis of their scores on 2
      composite measures: one assessing frontal lobe function and the other assessing
      medial temporal lobe function. The groups reflected the factorial combination of
      high and low functioning for each neuropsychological system, and they were tested
      on an event-based laboratory prospective memory task. High-functioning frontal
      participants showed better prospective remembering than low-functioning frontal
      participants. There was no significant difference in prospective memory
      performance attributable to medial temporal functioning. The results support the
      theoretical notion that frontal lobe processes play a key role in prospective
      remembering. Discussion focuses on the particular components of prospective
      memory performance that frontal lobes might mediate.

PMID- 10067782
TI  - Hemispheric asymmetries in vigilance and cerebral arousal mechanisms in younger
      and older adults.
AB  - Younger and older adults responded to an asterisk presented to either the left or
      right visual field, with delay interval between onset of a fixation cross and
      onset of the asterisk varied. At delay intervals longer than 3 s, reaction time
      was faster when the same visual field was stimulated on 2 successive trials than
      when different visual fields were stimulated. This prefield effect was larger in
      the left visual field (right hemisphere), consistent with hypotheses of
      hemispheric asymmetry for arousal and vigilance. For older adults, these results
      were obtained only when participants responded with the left hand, suggesting
      that some aspects of hemispheric asymmetry for attention-related processing or
      the efficiency of interhemispheric transfer may change in an age-related fashion.

PMID- 10067783
TI  - Testing normal older people three or four times at 1- to 2-year intervals:
      defining normal variance.
AB  - Normative data were presented that defined the upper and lower standards for
      deciding if cognitive abilities show reliable change over 2 or more testing
      occasions when retesting occurs at 1- to 2-year intervals. The Mayo Cognitive
      Factor Scores (MCFS; G. E. Smith et al., 1994) were analyzed because they permit
      the quantitation of overall functioning in 5 clinically important cognitive
      domains: established verbal knowledge, nonverbal reasoning, attention and
      concentration, new learning, and delayed memory. To the authors' knowledge, this
      is the first report of both group-level and individual-level data analyses
      derived from a respectably sized sample of normal persons who have been tested 3
      or more times at clinically common test-retest intervals.

PMID- 10067784
TI  - Manipulating attentional asymmetry affects self-reported arousal.
AB  - This investigation examined whether manipulating participants' attention toward
      the left or right visual field would have consequences for mood state. Based on
      the premise that right parietal activity is related to the arousal dimension of
      emotion, it was predicted that activating the right parietal region
      asymmetrically would differentially affect aspects of mood related to arousal.
      Half of the participants in the experiment completed a leftward-biased
      attentional orienting task, and half completed a mirror-image rightward-biased
      task. Consistent with predictions, participants in the left-biased group showed
      greater changes in self-reported arousal. Results support the notion of
      bidirectional causal relations between mood and perceptual asymmetries.

PMID- 10067785
TI  - Concept formation and concept shifting in frontal lesion and Parkinson's disease
      patients assessed with the California Card Sorting Test.
AB  - Concept formation and shifting abilities of 17 frontal lesion (FL) and 8
      Parkinson's disease (PD) patients were assessed with the California Card Sorting
      Test. FL patients demonstrated a significantly greater number of perseverative
      responses and deficits in strategy planning, strategy initiation, and concept
      formation and did not benefit from abstract cues in comparison with their matched
      normal control (NC) participants. PD patients also demonstrated an increased
      number of perseverative responses under selected conditions in comparison with
      their matched NCs, but their ability to explain their sorts, to extract and
      express the sorting principles, and to sort with the help of abstract and
      concrete cues depended on their general cognitive status.

PMID- 10067786
TI  - 1999 World Health Organization-International Society of Hypertension Guidelines
      for the Management of Hypertension. Guidelines Subcommittee.

PMID- 10067787
TI  - Pressor hyperreactivity to mental and hand-grip stresses in patients with
      hypercholesterolemia.
AB  - OBJECTIVE: To investigate the role of hypercholesterolemia in the regulation of
      blood pressure. SUBJECTS AND METHODS: We compared blood pressure responses to
      arithmetic stress and hand-grip tests in normotensive patients with
      hypercholesterolemia n = 15) and a mean (+/- SEM) age of 49 +/- 3 years, and
      normal cholesterolemic controls (n = 22) aged 48 +/- 1 years. Blood pressure and
      heart rate were measured throughout the tests. We examined the intracellular Ca2+
      concentration in platelets with or without low-density-lipoprotein stimulation
      (2.9 nmol/l, 10 mg/ml). The plasma nitrite plus nitrate and cyclic GMP were
      determined before and at the end of each test to evaluate nitric oxide production
      and activity. RESULTS: Both tests showed that systolic/diastolic blood pressure
      was higher in the hypercholesterolemic patients than in the normal controls
      (stress test: 139 +/- 3/91 +/- 4 versus 127 +/- 2/80 +/- 3 mmHg, P < 0.01/P <
      0.05; hand-grip test: 164 +/- 5/106 +/- 5 versus 144 +/- 3/88 +/- 3 mmHg, P <
      0.01/P < 0.01). The intracellular Ca2+ concentration in platelets and the
      increase in response to low-density-lipoprotein stimulation were higher in the
      hypercholesterolemic patients (without stimulation: 72 +/- 3 versus 64 +/- 3
      nmol/l, P < 0.01; with 2.9 nmol/l stimulation: 145 +/- 21 versus 89 +/- 6 nmol/l,
      P < 0.01). The increase in Ca2+ in response to 2.9 nmol/ml stimulation with low
      density lipoprotein was positively related to the increase in mean blood pressure
      in response to the stress test (r = 0.56, P < 0.002). Nitric oxide production
      appeared to be increased in the hypercholesterolemic patients (65 +/- 5 versus 51
      +/- 4 mmol/l, P < 0.05), and was not affected significantly by the tests. In
      contrast, cyclic GMP was lower in the patients and was increased significantly in
      the normal controls by the hand-grip test (P < 0.05). As a result, plasma cyclic
      GMP was lower in the patients (1.9 +/- 0.2 versus 2.5 +/- 0.1 nmol/l, P < 0.01).
      The ratio of plasma cyclic GMP to nitric oxide was also lower in the
      hypercholesterolemic patients at rest (P < 0.05), and at the end of the mental
      stress (P < 0.02) and hand-grip (P < 0.001) tests. CONCLUSIONS: Patients with
      hypercholesterolemia showed an exaggerated blood pressure response to both mental
      stress and exercise, even if resting blood pressure was normal. Increases in the
      intracellular Ca2+ concentration can contribute to these excessive responses. A
      disproportionately lower level of cyclic GMP to nitric oxide in plasma may also
      be involved in these abnormal responses.

PMID- 10067788
TI  - Job strain, blood pressure and response to uncontrollable stress.
AB  - OBJECTIVE: The association between cardiovascular disease risk and job strain
      (high-demand, low-control work) may be mediated by heightened physiological
      stress responsivity. We hypothesized that high levels of job strain lead to
      increased cardiovascular responses to uncontrollable but not controllable
      stressors. Associations between job strain and blood pressure reductions after
      the working day (unwinding) were also assessed. DESIGN: Assessment of
      cardiovascular responses to standardized behavioral tasks, and ambulatory
      monitoring of blood pressure and heart rate during a working day and evening.
      PARTICIPANTS: We studied 162 school teachers (60 men, 102 women) selected from a
      larger survey as experiencing high or low job strain. METHODS: Blood pressure,
      heart rate and electrodermal responses to an externally paced (uncontrollable)
      task and a self-paced (controllable) task were assessed. Blood pressure was
      monitored using ambulatory apparatus from 0900 to 2230 h on a working day.
      RESULTS: The groups of subjects with high and low job strain did not differ in
      demographic factors, body mass or resting cardiovascular activity. Blood pressure
      reactions to the uncontrollable task were greater in high than low job-strain
      groups, but responses to the controllable task were not significantly different
      between groups. Systolic and diastolic blood pressure did not differ between
      groups over the working day, but decreased to a greater extent in the evening in
      subjects with low job strain. CONCLUSIONS: Job strain is associated with a
      heightened blood pressure response to uncontrollable but not controllable tasks.
      The failure of subjects with high job strain to show reduced blood pressure in
      the evening may be a manifestation of chronic allostatic load.

PMID- 10067789
TI  - Adrenomedullin and membrane fluidity of erythrocytes in mild essential
      hypertension.
AB  - OBJECTIVE: Adrenomedullin is a newly discovered 52 amino acid peptide that has a
      potent vasodilating action. The present study was undertaken to investigate the
      role of adrenomedullin in the regulation of membrane fluidity of erythrocytes in
      patients with essential hypertension. METHODS AND RESULTS: We used an electron
      paramagnetic resonance and spin-labeling method. Adrenomedullin significantly
      decreased the order parameter for 5-nitroxide stearate and peak height ratio for
      16-nitroxide stearate obtained from electron paramagnetic resonance spectra of
      erythrocyte membranes in normotensive volunteers (mean +/- SEM order parameter
      value: control, 0.718 +/- 0.003, n = 16; adrenomedullin at 10(-9) mol/l, 0.692 +/
      0.004, n = 16, P < 0.05; adrenomedullin at 10(-8) mol/l, 0.690 +/- 0.004, n =
      16, P < 0.05; adrenomedullin at 10(-7) mol/l, 0.683 +/- 0.004, n = 16, P < 0.05).
      The findings showed that adrenomedullin increased the membrane fluidity of
      erythrocytes. In addition, the effect of adrenomedullin was significantly
      potentiated by prostaglandin E1 and dibutyryl cyclic AMP. In contrast, the
      calcium ionophore A23187 counteracted the actions of adrenomedullin. In patients
      with essential hypertension, who had higher order parameter values, the membrane
      fluidity of erythrocytes was significantly lower than in the normotensive control
      subjects (order parameter: 0.728 +/- 0.004 in hypertensives, n = 20; 0.692 +/-
      0.002 in normotensives, n = 36, P < 0.01). The effect of adrenomedullin on
      membrane fluidity was more pronounced in the erythrocytes of essential
      hypertensive than in the erythrocytes of normotensive subjects (change in the
      order parameter with adrenomedullin at 10(-9) mol/l: -4.2 +/- 0.3% in
      hypertensives, n = 20; -1.8 +/- 0.2% in normotensives, n = 20, P < 0.05;
      adrenomedullin at 10(-8) mol/l: -4.5 +/- 0.3% in hypertensives, n = 20; -1.8 +/-
      0.2% in normotensives, n = 36, P < 0.05). CONCLUSIONS: The results of the present
      study demonstrate that adrenomedullin significantly increased the membrane
      fluidity of erythrocytes. The mechanisms were partially mediated by a
      prostaglandin E1- and cyclic AMP-dependent pathway which might be linked to
      changes in intracellular calcium kinetics. The greater effect of adrenomedullin
      in patients with essential hypertension suggests that the peptide might actively
      participate in the regulation of membrane functions in hypertension.

PMID- 10067790
TI  - Analysis of circadian blood pressure rhythm and target-organ damage in stroke
      prone spontaneously hypertensive rats.
AB  - OBJECTIVE: We compared diurnal patterns of blood pressure in Wistar-Kyoto (WKY)
      rats, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously
      hypertensive rats (SHRSP), and analyzed the relationship between the change in
      diurnal patterns of blood pressure and target-organ damage in SHRSP. MATERIALS
      AND METHODS: Blood pressure, heart rate and motor activity in the three groups of
      rats were continuously monitored by radiotelemetry, from 1100 h on the first
      measuring day to 1300 h on the third measuring day. The left ventricular weight
      and the ratio of beta-myosin heavy chain to alpha-myosin heavy chain in the
      cardiac left ventricle, morphological changes in the glomerular basement membrane
      in the kidney, 24 h urinary protein excretion and brain weights were also
      measured in 10-, 12- or 17-week-old SHRSP. RESULTS: The SHR circadian blood
      pressure rhythm exhibited a pattern which peaked during the rats' active (light
      off or dark) phase, but the peak time was a little closer to the resting (light
      on) phase compared with that for WKY rats. Although the circadian blood pressure
      rhythm for 10-week-old SHRSP was similar to that observed for SHR, the patterns
      in 12- and 17-week-old SHRSP were shifted further towards the resting phase.
      Heart and left ventricular weight increased with the progression of hypertension.
      The ratio of beta- to alpha-myosin heavy chain in the left ventricle was higher
      in 12- and 17-week-old SHRSP than in 10-week-old SHRSP. Brain weight was
      increased significantly in 17-week-old SHRSP compared with 10- and 12-week-old
      SHRSP. Increased urinary protein excretion and morphological changes in the
      glomerular basement membrane in the kidney were observed in 12- and 17-week-old
      SHRSP. CONCLUSIONS: These data suggest that SHRSP have an abnormal circadian
      blood pressure rhythm associated with hypertensive target-organ damage. This rat
      strain may therefore be a useful model in which to investigate the mechanisms
      responsible for the alteration in the circadian blood pressure rhythm, and to
      analyze the relationship between the abnormal circadian rhythm and target-organ
      damage.

PMID- 10067791
TI  - Effects of antihypertensive therapy on factors mediating endothelium-dependent
      relaxation in rats treated chronically with L-NAME.
AB  - OBJECTIVES: To evaluate the relative participation of endothelium-derived factors
      mediating relaxation in response to acetylcholine in isolated mesenteric vascular
      beds from rats treated chronically with N(G)-nitro-L-arginine methylester (L
      NAME); and to compare the consequences of prolonged treatment with either an
      angiotensin converting enzyme inhibitor or a calcium channel blocker on the
      components of acetylcholine-induced relaxation in this vascular preparation.
      MATERIALS AND METHODS: Male Sprague- Dawley rats were treated for 8 weeks with L
      NAME (40 mg/kg per day), quinapril (10 mg/kg per day), diltiazem (100 mg/kg per
      day), L-NAME + quinapril and L-NAME + diltiazem. Systolic blood pressure was
      estimated by a tail-cuff plethysmograph. Relaxing responses to acetylcholine (10(
      12) to 10(-8) mol) in mesenteric vascular beds precontracted with phenylephrine
      (10(-5) mol/l) were studied in the presence and absence of L-NAME (10(-5) mol/l),
      L-NAME + indomethacin (10(-5) mol/l) or L-NAME + indomethacin + potassium
      chloride (6 x 10(-5) mol/l). The area under the dose- response curve was used to
      calculate the approximate participation of nitric oxide, prostaglandins or
      endothelium-derived hyperpolarizing factor in the acetylcholine-induced
      relaxation. RESULTS: Chronic administration of L-NAME increased blood pressure
      levels and vascular responsiveness to phenylephrine. Treatments with either
      quinapril or diltiazem reduced blood pressure levels and attenuated the increased
      response to phenylephrine. Relaxing responses to acetylcholine were similar in
      all groups, independently of the treatment received. The calculated participation
      of endothelium-derived hyperpolarizing factor in the acetylcholine-induced
      relaxation was higher than that of nitric oxide and prostaglandins in all groups,
      but was higher in L-NAME-treated than in untreated rats. In contrast, the
      participation of both nitric oxide and prostaglandins was higher in control than
      in L-NAME-treated rats. Quinapril increased the participation of prostaglandins
      in L-NAME-treated rats. Diltiazem increased the participation of nitric oxide in
      L-NAME-treated rats. CONCLUSIONS: The administration of L-NAME in Sprague-Dawley
      rats increased the production of endothelium-derived hyperpolarizing factor as a
      compensatory mechanism to maintain acetylcholine-induced relaxation.
      Antihypertensive therapy with either quinapril or diltiazem produced a selective
      redistribution of the endothelial factors mediating acetylcholine-induced
      relaxation.

PMID- 10067792
TI  - Effects of sodium depletion on the role of AT1- and alpha-adrenergic receptors in
      the regulation of forearm vascular tone in humans.
AB  - OBJECTIVE: Sodium depletion stimulates the renin-angiotensin and sympathetic
      nervous systems, which may affect the role of each of these systems in the
      regulation of vascular tone. We investigated the influence of sodium depletion on
      the roles of the angiotensin II type 1 receptor and the alpha1- and alpha2
      adrenergic receptors, and on nitric oxide generation, in the regulation of human
      forearm vascular tone. SUBJECTS AND METHODS: We studied the effects of the
      angiotensin II type 1 receptor antagonist losartan (0.1-3 microg/kg per min),
      angiotensin II (0.01-10 ng/kg per min), the alpha1- and alpha2-adrenoceptor
      antagonists doxazosin (3-100 ng/kg per min) and yohimbine (0.5-4 microg/kg per
      min) and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA;
      7.5-60 microg/kg per min) on forearm blood flow in control subjects (n = 12) and
      sodium-depleted subjects (n = 11). Sodium depletion was achieved by 3 days of
      pretreatment with 40 mg furosemide twice a day and a sodium-restricted diet.
      Forearm blood flow was measured by venous occlusion plethysmography. RESULTS:
      Sodium depletion resulted in activation of the renin-angiotensin and sympathetic
      nervous systems, as indicated by increased levels of plasma renin, aldosterone
      and heart rate (P < 0.05). Blood pressure remained unchanged. Losartan at the
      highest dose increased forearm blood flow in the sodium-depleted group by 42 +/-
      9%, but had no effect in controls (P < 0.05). Both doxazosin and yohimbine caused
      an increased vasodilatory effect in the sodium-depleted versus the control group
      (228 +/- 42 versus 83 +/- 13% and 192 +/- 24 versus 95 +/- 8%, respectively; P <
      0.05). The constrictor effects by angiotensin II and L-NMMA of -65 +/- 6% and -79
      +/- 4%, respectively, in controls were unchanged by sodium depletion.
      CONCLUSIONS: In sodium-depleted subjects, endogenous angiotensin II appears to
      play a role in the regulation of forearm vascular tone, in contrast to sodium
      replete conditions. Furthermore, in these subjects the role of alpha1- and alpha2
      adrenoceptors in the regulation of forearm vascular tone was enhanced compared
      with control conditions. Neither the forearm vascular effects of exogenously
      infused angiotensin II nor those of baseline nitric oxide production were
      influenced by sodium depletion.

PMID- 10067793
TI  - Influence of age and end-stage renal disease on the stiffness of carotid wall
      material in hypertension.
AB  - BACKGROUND: Incremental elastic modulus, which is the slope of the relationship
      between stress and strain of arterial vessels, is a marker of wall material
      stiffness. The radial artery incremental elastic modulus, which is not influenced
      by age, is normal or reduced in patients with essential hypertension but
      increased in patients with end-stage renal disease. Authors of studies on
      hypertension largely ignore the question of whether the incremental elastic
      modulus, measured in the common carotid artery as typical of a central artery
      site, differs according to age or to the presence of end-stage renal disease or
      both. SUBJECTS AND METHODS: The carotid incremental elastic modulus was measured
      in 208 hypertensive patients divided into four groups according to age (< or = or
      > 55 years) and the presence or absence of end-stage renal disease. The
      incremental elastic modulus was calculated from transcutaneous measurements of
      arterial internal diameter and wall thickness (echo-tracking device) and carotid
      pulse pressure (tonometry). Because the four groups of subjects had the same mean
      arterial pressure, the static incremental elastic modulus was calculated both in
      isobaric conditions and for the same wall stress. RESULTS: In nonuremic subjects,
      lumen diameter, wall thickness and the incremental elastic modulus were
      significantly (P < 0.001) increased in older subjects whereas compliance and
      distensibility were decreased. The mean (+/- SD) elastic modulus was 0.41 +/-
      0.14 x 10(3) kPa in younger and 0.71 +/- 0.28 x 10(3) kPa in older subjects. In
      uremic subjects, the corresponding values were 0.48 +/- 0.30 and 0.90 +/- 0.49 x
      10(3) kPa, and therefore higher than in nonuremic subjects, irrespective of age.
      Multiple regression analysis showed that age, mean arterial pressure and the
      presence of end-stage renal disease independently influenced carotid diameter,
      distensibility and the incremental elastic modulus. CONCLUSIONS: In hypertensive
      patients, the carotid incremental elastic modulus is increased independently in
      aging men and women and in the presence of uremia. This increase is not dependent
      on mechanical factors such as the level of mean blood pressure.

PMID- 10067794
TI  - An independent relationship between plasma leptin and heart rate in untreated
      patients with essential hypertension.
AB  - OBJECTIVE: To test the hypothesis that hemodynamic measurements in patients with
      essential hypertension are related independently to plasma leptin levels.
      PATIENTS AND METHODS: We measured plasma leptin, insulin, office and ambulatory
      blood pressure and heart rate in 60 men with untreated mild hypertension.
      RESULTS: Plasma leptin correlated significantly with body mass index (r = 0.43, P
      = 0.001), 24 h heart rate (r = 0.35, P = 0.006) and 24 h diastolic blood pressure
      (r = 0.27, P = 0.04) but not with age (r = 0.03; P = 0.85) or 24 h systolic blood
      pressure (r = -0.08, P = 0.56). Plasma leptin levels adjusted for body mass index
      correlated significantly with 24 h heart rate (r = 0.36, P = 0.005) but not with
      24 h diastolic blood pressure (r = 0.19, P = 0.15). We divided the patient
      population into tertiles of body mass index-adjusted plasma leptin levels. Age,
      plasma insulin, blood pressure, smoking status and physical activity habits were
      similar across the adjusted leptin tertiles. Patients from the third tertile of
      adjusted plasma leptin distribution (those with leptin levels higher than would
      be expected on the basis of body mass index) had significantly faster ambulatory
      heart rates than subjects from both the first and the second tertiles. The
      difference in heart rate across the three tertiles was most pronounced for the
      night-time values. CONCLUSIONS: In patients with essential hypertension, heart
      rate is faster in those patients with higher plasma leptin levels. This
      relationship is independent of age, body mass index, insulin levels, blood
      pressure level, smoking status and physical activity.

PMID- 10067795
TI  - Cardiovascular regulation during insulin infusion into the carotid or vertebral
      artery in dogs.
AB  - OBJECTIVE: To test the hypothesis that insulin increases heart rate and arterial
      pressure via direct effects on the central nervous system. METHODS AND DESIGN:
      Insulin was infused into the cerebral circulation of conscious dogs (n = 8)
      chronically instrumented for continuous infusions and measurement of arterial
      pressure, cardiac output, heart rate and other hemodynamic variables. In acute
      experiments, insulin was infused for 30 min into either a carotid or vertebral
      artery at several rates calculated to increase cerebral circulation insulin
      concentrations to levels in the physiological or pathophysiological range. It was
      infused with and without a simultaneous glucose infusion. During long-term
      experiments, insulin was infused into either a carotid or a vertebral artery for
      4 days at 0.4 or 0.2 mU/kg per min, respectively. RESULTS: Insulin infusion alone
      into the cerebral circulation produced no changes in any measured cardiovascular
      variable. A simultaneous glucose infusion also produced no changes in
      cardiovascular dynamics, except at the highest rate of infusion into the carotid
      artery. The changes seen at the highest rate of infusion are unlikely to be
      insulin-induced, since similar changes occurred when either glucose or saline was
      infused in the absence of any insulin infusion. Long-term insulin infusion (4
      days) into carotid or vertebral arteries also produced no changes in any measured
      cardiovascular or renal variable. CONCLUSIONS: These results provide no evidence
      that insulin, at physiological or pathophysiological concentrations, increases
      heart rate or arterial pressure by acting directly on the central nervous system,
      and suggest that sympathetic activation and tachycardia previously observed with
      systemic hyperinsulinemia may be secondary to peripheral actions of insulin.

PMID- 10067796
TI  - Temporal regulation of extracellular matrix components in transition from
      compensatory hypertrophy to decompensatory heart failure.
AB  - OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides
      tensile strength that allows cardiac muscle to perform systolic and diastolic
      functions. Collagen is induced during the transition from compensatory
      hypertrophy to heart failure. We hypothesized that cardiac stiffness during
      decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio.
      MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from
      spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory
      hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had
      decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto
      (WKY) rats were used as normotensive controls. In both SHR groups, increased
      levels of collagen were detected by immuno-blot analysis using type I collagen
      antibody. Elastin and collagen were quantitated by measuring
      desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To
      determine whether the decrease in elastin content was due to increased
      elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and
      elastin zymography on left ventricular tissue homogenates from control rats, SHR
      with compensatory hypertrophy and SHR with heart failure. RESULTS: The
      elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR
      without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in
      decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/-
      0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR
      with heart failure compared with controls (P < 0.001). The level of tissue
      inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and
      markedly reduced in heart failure. Decorin was strongly reduced in decompensatory
      heart failure compared with control hearts. CONCLUSIONS: Since collagen was
      induced in SHR with heart failure, decorin and elastin were decreased and the
      ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4
      were increased, we conclude that heart failure is associated with adverse
      extracellular matrix remodeling.

PMID- 10067797
TI  - In-vitro validation, with histology, of intravascular ultrasound in renal
      arteries.
AB  - OBJECTIVE: To investigate the feasibility of using intravascular ultrasound to
      characterize normal and diseased renal arteries. MATERIALS AND METHODS: Forty
      four renal artery specimens from 21 humans, removed at autopsy, were studied with
      intravascular ultrasound in vitro. From each vascular specimen, two to four sets
      of corresponding intravascular ultrasound images and histologic sections were
      subjected to qualitative analysis. The renal arterial wall was considered normal
      by intravascular ultrasound when the wall thickness (intima and media) was 0.5 mm
      or less. On intravascular ultrasound imaging, a distinction was made between
      bright lesions with or without peripheral shadowing (i.e. calcification).
      Histological sections were examined and fibromuscular lesions were scored with or
      without calcifications. Quantitative analysis of a multitude of intravascular
      ultrasound cross-sections (interval 5 mm) included assessment of the lumen area,
      vessel area, plaque area and percentage area obstructed. The target site
      (smallest lumen area) was compared with a reference site (largest lumen area
      before the first major side branch). RESULTS: Of the 130 corresponding
      intravascular ultrasound images and histologic sections analysed, 55 were normal
      and 75 presented a bright lesion on ultrasound; in 31 lesions, peripheral
      shadowing was involved. The sensitivity of the intravascular ultrasound in
      detecting calcifications was 87%, and the specificity was 89%. Lumen area
      reduction at the target site was associated with vessel and plaque area
      enlargement in eight specimens, with plaque area enlargement in 12 specimens and
      with a vessel area reduction in 21 specimens. CONCLUSIONS: Intravascular
      ultrasound is a reliable technique for distinguishing renal arteries with or
      without a lesion. Both plaque development and local vessel narrowing may result
      in renal artery stenosis.

PMID- 10067798
TI  - Renal angiotensin II receptor regulation and renin-angiotensin system inhibition
      in one-kidney, one clip hypertensive rats.
AB  - OBJECTIVE: To characterize glomerular and preglomerular vascular angiotensin II
      receptors during the acute phase of nonrenin-dependent one-kidney, one clip
      hypertension in rats, using the angiotensin II antagonists losartan and PD
      123319, and to investigate their regulation after renin-angiotensin system
      blockade with either an angiotensin converting enzyme inhibitor, captopril, or an
      angiotensin II receptor antagonist, TCV-116. MATERIALS AND METHODS: One-kidney,
      one clip hypertension was produced in male Sprague-Dawley rats by placing a
      silver clip (internal diameter 0.2 mm) on the left renal artery and removing the
      contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their
      glomerular and preglomerular vascular membranes were purified. Competitive
      binding studies were performed using specific angiotensin II antagonists.
      Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks
      before treatment with captopril or TCV-116 for 2 weeks. RESULTS: Competitive
      binding studies showed that only the angiotensin II type 1 (AT1) receptor was
      detected on both glomeruli and preglomerular vessels of all groups. The vascular
      AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one
      clip groups, but the glomerular receptor density was not different in these rats
      compared with age-matched uninephrectomized controls. The glomerular receptor
      density was significantly higher in captopril-treated rats and significantly
      lower in TCV-116-treated rats compared with untreated and control rats, but no
      significant changes were detected in any groups in vascular AT1 receptor density.
      CONCLUSIONS: Angiotensin II receptors on preglomerular vessels and glomeruli are
      differentially regulated during the early phase of hypertension and after renin
      angiotensin system blockade. Vascular angiotensin II receptors are upregulated in
      the early phase of hypertension whereas glomerular angiotensin II receptors are
      not However, after renin-angiotensin system blockade, glomerular but not vascular
      angiotensin II receptors were differentially regulated according to the type of
      blockade.

PMID- 10067799
TI  - Effect of endothelin blockade on pressure natriuresis in nitric oxide-deficient
      hypertensive rats.
AB  - OBJECTIVE: Chronic inhibition of nitric oxide synthesis has been shown to cause
      arterial hypertension and an important blunting of the pressure diuresis and
      natriuresis response. The mechanisms mediating these abnormalities are not
      completely established. We therefore studied the effects of endothelin on these
      alterations. MATERIALS AND METHODS: Pressure diuretic and natriuretic
      relationships were evaluated in rats treated chronically (3 weeks) with the
      nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME;
      40 mg/kg per day), alone or in combination with bosentan sodium salt (acute
      treatment: 10 mg/kg, intravenously; chronic treatment: 10 mg/kg per day).
      RESULTS: Chronic treatment with L-NAME significantly elevated mean arterial
      pressure (143.7 +/- 2.8 mmHg versus 102.8 +/- 1.6 in controls), reduced the
      glomerular filtration rate and renal blood flow and shifted the pressure diuretic
      and natriuretic responses to the right. Treatment with bosentan, either acute or
      chronically, did not attenuate the arterial hypertension of the L-NAME-treated
      rats but normalized the glomerular filtration rate and renal blood flow. In spite
      of the normalization of renal hemodynamics, the pressure diuretic and natriuretic
      responses of the bosentan-treated groups were not normalized, although chronic
      bosentan significantly improved the pressure natriuretic response. CONCLUSIONS:
      These results indicate that endothelin participates in the renal hemodynamic and
      excretory alterations that follow chronic inhibition of nitric oxide synthesis.
      However, the arterial hypertension is not mediated by endothelin activation.

PMID- 10067800
TI  - Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared
      with enalapril in elderly patients with primary hypertension. TEES Study Group.
AB  - OBJECTIVE: To assess the antihypertensive efficacy and safety of the novel AT1
      receptor antagonist, telmisartan, compared with that of enalapril in elderly
      patients with mild to moderate hypertension. DESIGN: A 26-week, multicenter,
      double-blind, parallel-group, dosage titration study. METHODS: A total of 278
      patients aged > or = 65 years were randomized to eithertelmisartan or enalapril
      once a day. The telmisartan dosage was increased from 20 to 40-80 mg and that of
      enalapril from 5 to 10-20 mg at 4-week intervals until trough supine diastolic
      blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5-25 mg
      once a day was added to the treatment regimen of those patients not controlled on
      monotherapy. RESULTS: Both treatments lowered blood pressure in a comparable and
      clinically meaningful manner. The adjusted mean changes from baseline in supine
      diastolic blood pressure at trough were -12.8 mmHg for telmisartan and -11.4 mmHg
      for enalapril (P = 0.074). Mean changes in supine systolic blood pressure were 
      22.1 mmHg for telmisartan and -20.1 mmHg for enalapril (P = 0.350). Overall, 63
      and 62% of patients responded to telmisartan and enalapril, respectively, with a
      supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective
      blood pressure lowering over the 24 h dosing interval, as determined by
      ambulatory blood pressure monitoring. Both regimens were well tolerated; however,
      patients on the enalapril regimen had more than double the incidence of treatment
      related cough compared with those on the telmisartan regimen (16 versus 6.5%).
      CONCLUSIONS: These results demonstrate that telmisartan is well tolerated and is
      at least as effective as enalapril in treating elderly patients with mild to
      moderate hypertension.

PMID- 10067801
TI  - Sphygmomanometry induces different blood pressure changes in normotensive and
      untreated (borderline) hypertensive subjects.

PMID- 10067802
TI  - Will the millimetre of mercury be replaced by the kilopascal?

PMID- 10067803
TI  - Women's choice between indigenous and Western contraception in urban Mozambique.
AB  - Research on women's reproductive behavior and family planning in developing
      countries is usually focused on western contraceptive methods and rarely
      addresses indigenous contraception, such as herbs, amulets, and charms that are
      believed to prevent pregnancy. However, the available data demonstrate that
      indigenous contraception is widely known, and its prevalence often rivals that of
      western methods. Based on qualitative data collected in Greater Maputo,
      Mozambique, in 1993, this study explores and analyzes women's choice between
      western methods-mainly oral contraceptives, intra-uterine devices and injectables
      available from state-run family planning clinics, and indigenous contraception, a
      combination of herbal and magical medicine, provided by traditional healers. The
      study demonstrates that women's choice between the two types of methods is
      determined by their sociodemographic characteristics and cultural background,
      access to these methods, perceptions of the effectiveness and undesirable side
      effects of these methods, and by restrictions imposed by the providers. Although
      indigenous methods may not compete with western contraception in the long run,
      their present-day persistence warrants the attention of scholars and policymakers
      who intend to integrate women's concerns and constraints in the design of family
      planning systems.

PMID- 10067804
TI  - Smoking behaviors of women whose children attend an urban pediatric primary care
      clinic.
AB  - OBJECTIVE: To characterize smoking behaviors of caregivers whose children attend
      a large urban pediatric primary care center. DESIGN: Descriptive survey. Women (n
      = 479) classified as smokers completed a questionnaire including demographics,
      smoking habits, measures of addiction, social reinforcers for smoking, attitudes
      and knowledge, other health and safety habits, and the pediatrician's role in
      smoking cessation counseling. RESULTS: Of 1421 women surveyed, 36.6% (517) were
      classified as daily smokers. Four hundred and seventy-nine (93%) were enrolled in
      the study. Thirty-eight (7%) refused or were ineligible. Smokers differed
      significantly from non-smokers, with smokers more likely to have lower incomes
      (p<.03), lower educational attainment (p<.001), and were more likely to be white
      than non-smokers (p<.001). The average smoker smoked 14 cigarettes per day for 10
      years. Half of the subjects had not considered quitting smoking in the near
      future. The majority of subjects (66%) lived with at least one other smoker, and
      reported that more than half of their friends smoked. Most (79%) participants
      agreed that pediatricians should give smoking cessation advice to parents of
      their patients. However, only 19% recalled being counseled to quit, and 55%
      recalled their child's doctor discussing the danger of environmental tobacco
      smoke. CONCLUSION: The pediatric visit is an excellent opportunity for
      identifying women who smoke. Efforts to assist women with smoking cessation in
      similar settings will need to take into account their poverty and the high degree
      of social support for their continued smoking.

PMID- 10067805
TI  - Sexual harassment in academia: a hazard to women's health.
AB  - Universities and colleges have for a long time ignored sexual harassment, hoped
      it was non-existent or waited for it to disappear. Recently, however, students,
      professors and university administrators have begun to recognize the
      perniciousness and pervasiveness of the problem but thus far with little
      attention to sexual harassment as a health hazard. Based on data collected by
      questionnaire from 455 women university undergraduate and graduate students and
      nine follow-up in-depth interviews, this study examines the dimensions and
      dynamics of sexual harassment as a health hazard for women. Sexual harassment is
      found to have both direct and indirect health effects, including nausea and
      sleeplessness, loss of self-esteem, fear and anger, feelings of helplessness and
      isolation, as well as nervousness and depression. In contributing to the
      literature on women's culturally and socially determined health problems, this
      study sheds light on the ways in which women students' economic, political,
      social and personal well-being can be undermined by sexual harassment.

PMID- 10067806
TI  - Rural women's satisfaction and stress as family health care gatekeepers.
AB  - Women shoulder much of the responsibility for their families' health care, making
      women's satisfaction with available services an important issue for their
      families and for women's personal stress levels. Lack of services and resulting
      stress may be acute for rural women, the focus of this study. In a state-wide
      survey, fewer than one-half of rural women were satisfied with the health
      services available; dissatisfaction was a strong determinant of women's stress
      over health care issues. Rural women are at risk for a pile-up of stressors that
      could impede their ability to care for themselves and their families.

PMID- 10067807
TI  - Migraine: a "woman's disease?".
AB  - Migraine, a chronic disorder characterized by episodes of headache, has a
      profound effect on the well-being and general functioning of its victims, not
      only during the acute attacks, but also in terms of impairment of school
      achievement, work performance, and family/social relationships. Despite
      staggering social and economic costs, it remains under-diagnosed and under
      treated worldwide. Migraine has been labeled a "woman's disease" because it is
      three times more common in women than men, the attacks tend to be more severe and
      disabling among women and, in some women, they seem to be modulated by such
      hormonal "milestones" as menarche, menstruation, pregnancy and menopause. After a
      brief review of the diagnosis of migraine, this article will examine the nuances
      responsible for that label and their implications for treatment.

PMID- 10067808
TI  - Moderate physical activity in relation to mammographic patterns.
AB  - High-risk mammographic patterns may be used as a surrogate end point for breast
      cancer in etiologic research as well as in prevention studies. Physical activity
      may be one of the few modifiable risk factors for breast cancer. We examined the
      relationship between physical activity and mammographic patterns among 2720
      Norwegian women, ages 40-56 years, who participated in both the Second and Third
      Tromso studies. Epidemiologic data were obtained through questionnaires. Two
      questions from the Second Tromso study and five questions from the Third elicited
      information on physical activity. The mammograms were categorized into five
      groups based on anatomical-mammographic correlations. For analysis, patterns I
      through III were combined into a low-risk group and patterns IV and V into a high
      risk group. Odds ratios that were adjusted for age, education, menopausal status,
      body mass index, parity, age at menarche, oral contraceptive use, and alcohol
      intake, with 95% confidence intervals, were estimated using logistic regression.
      Women who reported moderate physical activity, i.e., more than 2 h/week, were 20%
      less likely (odds ratio, 0.8; 95% confidence interval, 0.6-1.1) to have high-risk
      mammographic patterns compared with those who reported being inactive. This
      relationship remains consistent when stratified by menopausal status, parity, and
      tertiles of body mass index. However, all of the associations between various
      measures of physical activity and high-risk patterns found in this study are weak
      with confidence intervals that include 1.0. Thus, chance is a reasonable
      explanation for the weak associations found. The relationship between physical
      activity and high-risk patterns should be examined further as a means to explore
      the biologic mechanisms relating physical activity to breast cancer risk.

PMID- 10067809
TI  - Macronutrient intake and change in mammographic density at menopause: results
      from a randomized trial.
AB  - To examine the effects of dietary fat intake on breast cancer risk, we are
      conducting a randomized trial of dietary intervention in women with extensive
      areas of radiologically dense breast tissue on mammography, a risk factor for
      breast cancer. Early results show that after 2 years on a low-fat, high
      carbohydrate diet there is a significant reduction in area of density,
      particularly in women going through menopause. In women who went through
      menopause during the 2-year follow-up, the mean decreases in area of density and
      percentage of density in the intervention group were 11.0 cm2 and 11.0%,
      respectively, whereas the control group decreased 4.5 cm2 and 5.2%. The purpose
      of this analysis was to determine whether changes in intake of specific
      macronutrients could account for the observed reduction in breast density in
      these women. Differences between 2-year and baseline values of macronutrients
      (averaged over 3 nonconsecutive days of food intake) were calculated. We examined
      the effect of dietary variables, adjusted for changes in total calorie intake and
      weight and for family history of breast cancer, on changes in area of density and
      percentage of density using linear regression. Reduction in total or saturated
      fat intake or cholesterol intake was significantly associated with decreased
      dense area (p < or = .004). The most significant dietary variable associated with
      reduction in percentage of density was reduction in dietary cholesterol intake (P
      = 0.001), although reducing saturated fat intake was of borderline significance
      (P = 0.05). The effect of the membership in the intervention and control groups
      on change in area of density or percentage of density was reduced by models that
      included changes in intake of any fat, or cholesterol, or carbohydrates. The
      observation of an effect of diet at menopause on breast density, a marker of
      increased risk of breast cancer, may be an indication that exposures at this time
      have an enhanced effect on subsequent risk.

PMID- 10067810
TI  - Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with
      stage III or IV epithelial ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) has a high mortality rate, which is due primarily
      to the fact that early clinical symptoms are vague and nonspecific; hence, this
      disease often goes undetected and untreated until in its advanced stages.
      Sensitive and reliable methods for detecting earlier stages of EOC are,
      therefore, urgently needed. Epidermal growth factor (EGF) is a ligand for EGF
      receptor (ErbB1); this receptor is the product of the c-erbB1 proto-oncogene.
      ErbB1 overexpression is common in human ovarian carcinoma-derived cell lines and
      tumors, in which overexpression is thought to play a critical role in tumor
      etiology and progression. Furthermore, ErbB1 overexpression is associated with
      disease recurrence and decreased patient survival. Recently, we have developed an
      acridinium-linked immunosorbent assay that detects a approximately 110-kDa
      soluble analogue of ErbB1, ie., sErbB1, in serum samples from healthy men and
      women (A. T. Baron, et al., J. Immunol. Methods, 219: 23-43, 1998). Here, we
      demonstrate that serum p110 sErbB1 levels are significantly lower in EOC patients
      with stage III or IV disease prior to (P < 0.0001) and shortly after (P < 0.0001)
      cytoreductive staging laparotomy than in healthy women of similar ages, whereas
      EGF levels are significantly higher than those of age-matched healthy women only
      in serum samples collected shortly after tumor debulking surgery (P < 0.0001). We
      observe that the preoperative serum sErbB1 concentration range of advanced stage
      EOC patients barely overlaps with the serum sErbB1 concentration range of healthy
      women. In addition, we show that serum sErbB1 and EGF levels changed temporally
      for some EOC patients who were surgically debulked of tumor and who provided a
      second serum sample during the course of combination chemotherapy. Finally, we
      observe a significant positive association between sErbB1 and EGF levels only in
      serum samples of EOC patients collected prior to cytoreductive surgery
      (correlation coefficient = 0.61968; P = 0.0027). These data suggest that
      epithelial ovarian tumors concomitantly affect serum sErbB1 and EGF levels. In
      conclusion, these data indicate that serum sErbB1 and EGF (postoperative only)
      levels are significantly different between EOC patients and healthy women and
      that altered and/or changing serum sErbB1 and EGF levels may provide important
      diagnostic and/or prognostic information useful for the management of patients
      with EOC.

PMID- 10067811
TI  - Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin
      induced cytochrome P450 1B1 expression in human lymphocytes.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a
      broad spectrum of biological responses, including altered metabolism, disruption
      of normal hormone signaling pathways, reproductive and developmental effects, and
      cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in
      the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen.
      Therefore, the analysis of CYP1B1 in humans may be useful in establishing
      relationships between dioxin exposure and adverse health effects. In this study,
      we examined the expression of CYP1B1 in human peripheral blood lymphocytes of
      unexposed individuals using a quantitative reverse transcription-PCR method.
      Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear
      cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated
      lymphocytes with TCDD for 1-5 days of culture resulted in a peak induction of
      CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture
      was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied
      greatly among different individuals. However, the half maximal dose required for
      this induction was similar between individuals and comparable to that observed in
      the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1
      exhibits variable constitutive expression and is inducible in vitro by TCDD in
      human lymphocytes and that the magnitude of induction varies within the
      population. These data define the suitability of CYP1B1 for use as a
      mechanistically based biomarker in ongoing molecular epidemiological studies of
      human populations exposed to dioxins and related chemicals that bind the aromatic
      hydrocarbon receptor.

PMID- 10067812
TI  - Laboratory assay reproducibility of serum estrogens in umbilical cord blood
      samples.
AB  - We evaluated the reproducibility of laboratory assays for umbilical cord blood
      estrogen levels and its implications on sample size estimation. Specifically, we
      examined correlation between duplicate measurements of the same blood samples and
      estimated the relative contribution of variability due to study subject and assay
      batch to the overall variation in measured hormone levels. Cord blood was
      collected from a total of 25 female babies (15 Caucasian and 10 Chinese-American)
      from full-term deliveries at two study sites between March and December 1997. Two
      serum aliquots per blood sample were assayed, either at the same time or 4 months
      apart, for estrone, total estradiol, weakly bound estradiol, and sex hormone
      binding globulin (SHBG). Correlation coefficients (Pearson's r) between duplicate
      measurements were calculated. We also estimated the components of variance for
      each hormone or protein associated with variation among subjects and variation
      between assay batches. Pearson's correlation coefficients were >0.90 for all of
      the compounds except for total estradiol when all of the subjects were included.
      The intraclass correlation coefficient, defined as a proportion of the total
      variance due to between-subject variation, for estrone, total estradiol, weakly
      bound estradiol, and SHBG were 92, 80, 85, and 97%, respectively. The magnitude
      of measurement error found in this study would increase the sample size required
      for detecting a difference between two populations for total estradiol and SHBG
      by 25 and 3%, respectively.

PMID- 10067813
TI  - Merkel cell carcinoma and melanoma: etiological similarities and differences.
AB  - Merkel cell carcinoma (MCC) of the skin and cutaneous malignant melanoma can now
      be compared epidemiologically through the use of population-based data not
      previously available for MCC. The results may provide new clues to etiology. In
      this study, United States data covered by the Surveillance, Epidemiology, and End
      Results (SEER) Program were from nine areas of the United States (approximately
      10% of the population). In 1986-1994, 425 cases of MCC were registered. The
      annual age-adjusted incidence per 100,000 of MCC was 0.23 for whites and 0.01 for
      blacks; among whites, the ratio of melanoma to MCC was approximately 65 to 1.
      Only 5% of MCC occurred before age 50, unlike the lifelong risk of nodular and
      superficial spreading melanoma. Regional incidence rates of both cancers
      increased similarly with increasing sun exposure as measured by the UVB solar
      index. The most sun-exposed anatomical site, the face, was the location of 36% of
      MCC but only 14% of melanoma. Both cancers increased in frequency and
      aggressiveness after immunosuppression and organ transplantation (36 cases from
      the Cincinnati Transplant Tumor registry and 12 from published case reports) and
      after B-cell neoplasia (5 cases in this study; 13 from case series in the
      literature). The SEER data contained reports of six patients with both types of
      cancer; 5 melanomas before the diagnosis of MCC and 1 after diagnosis. MCC and
      melanoma are similarly related to sun exposure and immunosuppression, but they
      differ markedly from one another in their distributions by age, race, and
      anatomical site, especially the face.

PMID- 10067814
TI  - Five caffeine metabolite ratios to measure tobacco-induced CYP1A2 activity and
      their relationships with urinary mutagenicity and urine flow.
AB  - To choose a sensitive protocol to discriminate populations exposed and not
      exposed to inducers, five urinary metabolite ratios (MRs) [MR1 (17X + 17U)/137X,
      MR2 (5-acetylamino-6-formylamino-3-methyluracil [AFMU] + 1X + 1U)/17U, MR3
      (17X/137X), MR4 (AFMU + 1X + 1U + 17X + 17U)/137X, and MR5 (AFMU + 1X + 1U)/17X]
      were calculated in 4-5 h and 0-24 h urine samples after caffeine intake. One
      hundred twenty-five healthy volunteers (59 nonsmokers and 66 smokers) were
      included in the study. All ratios showed a log-normal distribution. MR2 in the
      two time intervals was the only ratio nondependent on the urine flow. Differences
      between nonsmokers and smokers could be detected with all ratios at 4-5 h.
      However, only MR2 and, to a lesser extent, MR5 allowed the discrimination of
      higher cytochrome P450 1A2 (CYP1A2) activity in smokers in the 0-24 h sample.
      Although smokers had increased urinary mutagenicity in relation to nonsmokers, a
      significant association between MRs and urine mutagenicity was observed only with
      MR2 in the 4-5 h interval; this ratio/time schedule being that of higher
      association with tobacco consumption. The most flow-dependent ratios, MR1, MR3,
      and MR4, were closely correlated with each other at the two intervals. The flow
      dependency profile of each ratio may explain their different power to indicate
      both tobacco exposure and tobacco-derived mutagenicity. In conclusion, MR2 in the
      period of 4-5 h after caffeine intake seems preferable, especially at high urine
      flow rates.

PMID- 10067815
TI  - KRAS mutations predict progression of preneoplastic gastric lesions.
AB  - Eight hundred sixty-three subjects with atrophic gastritis were recruited to
      participate in an ongoing chemoprevention trial in Narino, Colombia. The
      participants were randomly assigned to intervention therapies, which included
      treatment to eradicate Helicobacter pylori infection followed by daily dietary
      supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design.
      A series of biopsies of gastric mucosa were obtained according to a specified
      protocol from designated locations in the stomach for each participant at
      baseline (before intervention therapy) and at year three. A systematic sample of
      160 participants was selected from each of the eight treatment combinations. DNA
      was isolated from each of these biopsies (n = 320), and the first exon of KRAS
      was amplified using PCR. Mutations in the KRAS gene were detected using
      denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of
      all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those
      participants with atrophic gastritis without metaplasia, 19.4% (6 of 25)
      contained KRAS mutations, indicating that mutation of this important gene is
      likely an early event in the etiology of gastric carcinoma. An important
      association was found between the presence of KRAS mutations in baseline biopsies
      and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of
      participants without baseline KRAS mutations progressed from atrophic gastritis
      to intestinal metaplasia or from small intestinal metaplasia to colonic
      metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a
      more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05);
      multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the
      specificity of the KRAS mutation predicted progression. For those participants
      with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17)
      progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-
      >A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR,
      8.7; P = 0.004 using chi2 test).

PMID- 10067816
TI  - Risk factors for abnormal anal cytology in young heterosexual women.
AB  - Although anal cancers are up to four times more common in women than men, little
      is known about the natural history of anal human papillomavirus (HPV) infections
      and HPV-related anal lesions in women. This study reports on the prevalence of
      and risks for anal cytological abnormalities over a 1-year period in a cohort of
      young women participating in a study of the natural history of cervical HPV
      infection. In addition to their regularly scheduled sexual behavior interviews
      and cervical testing, consenting women received anal HPV DNA and cytological
      testing. Anal cytology smears were obtained from 410 women whose mean age was
      22.5 +/- 2.5 years at the onset of the study. Sixteen women (3.9%) were found to
      have abnormal anal cytology: 4 women had low-grade squamous intraepithelial
      lesions (SILs) or condyloma; and 12 women had atypical cells of undetermined
      significance. Factors found to be significantly associated with abnormal anal
      cytology were a history of anal sex [odds ratio (OR), 6.90; 95% confidence
      interval (CI), 1.7-47.2], a history of cervical SILs (OR, 4.13; 95% CI, 1.3
      14.9), and a current anal HPV infection (OR, 12.28; 95% CI, 3.9-43.5). The strong
      association between anal intercourse and the development of HPV-induced SILs
      supports the role of sexual transmission of HPV in anal SILs. Young women who had
      engaged in anal intercourse or had a history of cervical SILs were found to be at
      highest risk.

PMID- 10067817
TI  - Environmental contaminants and body fat distribution.
AB  - The effect of body mass index (BMI) and waist:hip ratio (WHR) on plasma levels of
      organochlorines [i.e., 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)] was
      investigated in a sample of black and white women drawn from a population-based
      study in North Carolina. Organochlorine levels were determined in plasma samples
      from 99 women selected on the basis of race (black versus white) and quartile of
      the WHR (1st versus 4th). Of a panel of 20 organochlorine compounds tested, only
      DDE was detectable in most study subjects. Measurements of height, weight, and
      waist and hip circumferences were taken during an in-person interview.
      Information was elicited regarding dietary, residential, and breast-feeding
      histories. Results of multiple regression analyses indicate that black women had
      significantly higher plasma levels of DDE than white women. These levels were
      independent of BMI and WHR. BMI but not WHR was also found to be an independent
      predictor of DDE plasma level. These results suggest that black/white differences
      should be considered in studies that explore the relationship between
      environmental contaminants and various disease outcomes, such as breast cancer
      risk. In addition, BMI may affect circulating levels of contaminants and should
      also be considered a potentially important modifying factor for exposure to
      lipophilic substances.

PMID- 10067818
TI  - Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk.
AB  - Glutathione S-transferases (GSTs) are involved in detoxification of reactive
      metabolites of carcinogens and, therefore, could be potentially important in
      susceptibility to cancer. The associations between larynx cancer risk and GSTM3
      and GSTP1 gene polymorphisms, either separately or in combination with GSTM1 and
      GSTT1 gene polymorphisms, were evaluated using peripheral blood DNA from 129
      cancer patients and 172 controls, all regular smokers. The frequencies of GSTM3
      AA, AB, and BB genotypes were 60.5%, 36.4%, and 3.1% in cases and 72.7%, 24.4%,
      and 2.9% in controls, respectively. The frequencies of GSTP1 AA, AG, and GG
      genotypes were 48.1%, 40.3%, and 11.6% in cases and 50.0%, 37.2%, and 12.8% in
      controls, respectively. Multivariate logistic regression analyses did not reveal
      any association between the GSTP1 (AG or GG) genotype and larynx cancer [odds
      ratio, 1.1; 95% confidence interval (CI), 0.7-2.0]. In contrast, a significant
      increase in risk was related to the GSTM3 (AB or BB) genotype (odds ratio, 2.0;
      95% CI, 1.1-3.4). The combined GSTM3 (AB or BB) and GSTM1-null genotype conferred
      a 4-fold risk (95% CI, 1.6-10.1) of larynx cancer as compared with the combined
      GSTM3 AA and GSTM1-positive genotype. However, the effect of GSTM3 (AB or BB)
      genotype was similar among individuals with GSTM1-positive or GSTM1-null
      genotypes.

PMID- 10067819
TI  - Screening for neuroblastoma: progress and pitfalls.

PMID- 10067821
TI  - Pulsatility in primates--a perspective from the placode.

PMID- 10067822
TI  - Differential effects of superior and inferior spermatic nerves on testosterone
      secretion and spermatic blood flow in cats.
AB  - It has been postulated that testosterone secretion is partially regulated by
      signals from the spermatic nerves. To further examine this hypothesis in vivo,
      the superior (SSN) or the inferior (ISN) spermatic nerves were stimulated
      electrically (varying intensity, 25 Hz, 0.2 msec, 10 min) in anesthetized cats,
      determining the testosterone concentration and the blood flow in the spermatic
      vein. In some additional experiments arterial blood was sampled, and
      norepinephrine (NE) output was calculated. Stimulation of the SSN (25-35 V)
      increased the testosterone concentration in spermatic vein blood (P < 0.01
      compared with prestimulation levels). The response varied among animals, reaching
      a 50-100% increase in some animals, whereas in others it ranged from almost
      undetectable to more than 10 ng/100 g x min. Under the same experimental
      conditions, the NE output increased from 135.4 +/- 99 to 1614.2 +/- 347 pg/ml (P
      < 0.01), and spermatic blood flow decreased from 24.1 +/- 1.42 to 20.2 +/- 1.65
      ml/min x 100 g (P < 0.05) during nerve stimulation. By contrast, stimulation of
      the ISN (25-35 V) modified neither the testosterone concentration, the NE output,
      nor the blood flow in the spermatic vein. High intensity stimulation (36-70 V) of
      each spermatic nerve evoked different vascular and hormonal effects. SSN
      activation induced a marked decrease in spermatic blood flow during stimulation
      and an increase in the testosterone response, whereas ISN activation resulted
      only in an enhanced spermatic blood flow. Our results suggest that testosterone
      secretion, although mainly dependent on gonadotropin secretion, could be further
      regulated by neural inputs from the SSN acting directly or alternatively through
      changes in blood flow. It would appear that the SSN mainly supplies the
      vasoconstrictor fibers to the testis, whereas the ISN provides vasodilator
      fibers.

PMID- 10067823
TI  - Inhibition of dendritic spine induction on hippocampal CA1 pyramidal neurons by a
      nonsteroidal estrogen antagonist in female rats.
AB  - Estrogens regulate the formation of excitatory synaptic connections in the
      hippocampus of female rats. Because the adult hippocampus has a very low
      concentration of intracellular estrogen receptors, it is unclear whether a
      conventional genomic mechanism is involved. Nonsteroidal estrogen antagonists are
      useful tools to study estrogen action because they can provide pharmacological
      data in favor of a particular pathway of estrogen action and evidence against
      other pathways. To investigate the role of intracellular estrogen receptors in
      the estrogen induction of synapse formation, we took advantage of previous
      studies in which we had shown that an estrogen antagonist, CI-628, enters the
      brain and blocks estrogen induction of progestin receptors to study whether the
      same antagonist would either mimic or block effects of estradiol to induce
      excitatory spine synapses. Using silver impregnation of neurons by the single
      section Golgi technique and morphometric analysis, we found that CI-628
      effectively prevented estrogen induction of spines on CA1 pyramidal neurons,
      without having any agonist effects of its own. This result is consistent with an
      action of estradiol via intracellular estrogen receptors that are known to be
      expressed by interneurons within the hippocampus.

PMID- 10067824
TI  - Regulation of estrogen sulfotransferase expression in Leydig cells by cyclic
      adenosine 3',5'-monophosphate and androgen.
AB  - Estrogen sulfotransferase (EST) catalyzes the specific sulfonation and
      inactivation of estrogens. A common site for EST expression in mammalian species
      is the testicular Leydig cells. In previous in vivo studies, we have shown that
      testicular expression of EST is under the regulation of LH. Thus, EST expression
      in mouse Leydig cells was abolished by hypophysectomy, but could be restored by
      hCG injection. In this study, we have evaluated the downstream mechanisms by
      which LH exerts its regulatory effect on EST. Primary mouse Leydig cells were
      isolated and purified by collagenase digestion and Percoll density gradient
      centrifugation. They were cultured in serum-free medium at 32 C and treated with
      various agents for 24 or 48 h, and levels of EST messenger RNA and enzyme
      activity were determined. Consistent with the in vivo data suggesting an
      essential role of LH in regulating EST expression, treatment of primary mouse
      Leydig cells in vitro with 100 microM 8-bromo-dibutyryl cAMP [(Bu)2cAMP]
      increased EST expression 3- to 5-fold. The effect of (Bu)2cAMP was attenuated by
      the steroidogenesis inhibitor aminoglutethimide and was mimicked by the potent
      androgen 5alpha-dihydrotestosterone (5-DHT). The activity of 5-DHT in stimulating
      EST expression was blocked by the androgen receptor antagonist, hydroxyflutamide.
      These data suggested the involvement of androgen in (Bu)2cAMP-induced EST
      expression. Further evidence came from the study with interleukin-1beta, another
      agent known to suppress Leydig cell steroidogenesis by down-regulating P450c17
      gene expression. Treatment of Leydig cells with 0.2 ng/ml interleukin-1beta
      inhibited (Bu)2cAMP-induced EST expression, which was overcome by the addition of
      5-DHT. Finally, in the testis-feminized mouse (Tfm) in which the androgen
      receptor is nonfunctional due to a frameshift mutation, testicular EST expression
      is completely absent, whereas messenger RNAs of steroidogenic enzymes such as
      P450c17 and 3beta-hydroxysteroid dehydrogenase are relatively abundant. We
      conclude that, by acting as an autocrine or paracrine factor, androgen plays an
      essential role in the regulation of estrogen sulfotransferase expression in
      Leydig cell by LH and cAMP.

PMID- 10067825
TI  - Cloning of thyrotropin-releasing hormone precursor and receptor in rat thymus,
      adrenal gland, and testis.
AB  - TRH is a hypophysiotropic peptide that acts mainly via the hypothalamic-pituitary
      thyroid axis, but TRH immunoreactivity is also detected in several peripheral
      tissues. PCR with two pairs of primers enabling amplification of three fragments
      of TRH complementary DNA (cDNA) was used to demonstrate local production of TRH.
      Products of the expected size were detected in the testis, adrenal gland,
      lymphoid organs, thymus, and spleen. The amplified cDNA fragments were cloned and
      sequenced to show that the TRH gene is expressed in the thymus, spleen, and
      adrenal gland. Competitive RT-PCR showed that the TRH messenger RNA content of
      the testis was about one third that of the hypothalamus, whereas the adrenal
      gland contained 2% and the thymus 6%. HPLC analysis of thymus and spleen extracts
      showed small amounts of TRH, with a particular processing pattern of pro-TRH in
      lymphoid organs. The expression of the TRH receptor gene in peripheral organs was
      investigated to determine whether TRH had an autocrine or a paracrine action.
      cDNA fragments that encompassed the coding region of the receptor were identified
      in the testis, adrenal gland and thymus. No signal was detected in the spleen.
      These findings indicate that TRH may have a biological activity in extrapituitary
      organs and may act locally in the testis, adrenal gland, and thymus.

PMID- 10067826
TI  - Calcitonin-dependent down-regulation of the mouse C1a calcitonin receptor in
      cells of the osteoclast lineage involves a transcriptional mechanism.
AB  - Although expression of the calcitonin (CT) receptor (CTR) decreases after CT
      binding, there has been no evidence that it occurs at the transcriptional level.
      In the present study we investigated the mechanism of CTR messenger RNA (mRNA)
      down-regulation by CT in mouse cocultures of bone marrow and osteoblasts.
      Ribonuclease protection analysis revealed that osteoclast-like cells purified
      from cocultures predominantly express the C1a isoform and do not express an
      appreciable amount of the brain-specific C1b mRNA (< 1% of C1a). Treatment of day
      5 cocultures with CT caused a dose- and time-dependent decrease in the steady
      state level of C1a mRNA. This CT effect was mimicked by the cAMP agonists
      forskolin and (Bu)2cAMP. Prolonged suppression of C1a mRNA was observed after
      short treatment with CT, but not with (Bu)2cAMP, suggesting that persistent
      intracellular cAMP elevation is necessary for the prolonged CT effect. The half
      life of the C1a mRNA in cocultures was 4-6 h and was not altered by CT or
      (Bu)2cAMP. Moreover, competitive RT-PCR analysis revealed that 1-h treatment with
      CT reduced the level of CTR heterogeneous nuclear RNA to 10% in a cycloheximide
      independent manner. These results suggest that CT down-regulates C1a-CTR mRNA
      expression at least in part by a transcriptional mechanism, thereby contributing
      to the ligand-induced desensitization in cells of the osteoclast lineage.

PMID- 10067827
TI  - Fibroblast growth factor-2 induces hepatocyte growth factor/scatter factor
      expression in osteoblasts.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth
      factor with a major role in tissue morphogenesis and repair. It stimulates the
      proliferation of cells of the osteoblast and osteoclast lineages. Mitogenic
      factors playing a role in fracture repair may act by regulating HGF/SF expression
      or activity in bone-forming cells. We investigated the effect of fibroblast
      growth factor-2 (FGF-2) on the expression of HGF/SF and its receptor, encoded by
      c-met, in the MC3T3-E1 osteoblastic cell line. MC3T3-E1 cells expressed low
      levels of HGF/SF messenger RNA (mRNA), which were markedly increased by FGF-2 in
      a dose- and time-dependent manner. FGF-2 also induced HGF/SF polypeptide
      synthesis. The stimulation of HGF/SF mRNA expression by FGF-2 was blocked by
      cycloheximide, a protein synthesis inhibitor, but not by DNA or prostaglandin
      synthesis inhibitors. FGF-2 increased the rate of HGF/SF gene transcription by
      approximately 2-fold, as determined by nuclear run-on assays, and did not modify
      the decay of HGF/SF mRNA in transcriptionally arrested cells. FGF-2 also caused a
      dose- and time-dependent stimulation of c-met mRNA. In conclusion, FGF-2 induces
      HGF/SF expression in osteoblasts and may promote HGF/SF activity by increasing
      the expression of its receptor. Through these mechanisms, HGF/SF could mediate
      FGF actions on bone repair.

PMID- 10067828
TI  - Retinol-binding protein is produced by rabbit chondrocytes and responds to
      parathyroid hormone (PTH)/PTH-related peptide-cyclic adenosine monophosphate
      pathway.
AB  - PTH and dibutyryl cAMP [(Bu)2cAMP] induced the expression of a 19-kDa protein in
      the conditioned media of rabbit growth plate chondrocyte cultures. The 19-kDa
      protein was identified as plasma retinol-binding protein (RBP) by aminoterminal
      sequence analysis and immunoblot analysis with an anti-RBP monoclonal antibody.
      Northern blot analysis showed that PTH, PTH-related peptide (PTHrP), and
      (Bu)2cAMP increased the RBP messenger RNA (mRNA) level in chondrocyte cultures.
      Further, both PTH and (Bu)2cAMP markedly induced the expression of RBP mRNA by
      about 10-fold at 3 h and by about 40-fold at 24 h, indicating a pretranslational
      regulation. The level of the mRNA expression induced by PTH, PTHrP, and (Bu)2cAMP
      was as high as that by retinoic acid (RA), known as a potent inducer of RBP in
      hepatoma cells. RBP mRNA was also detected in cartilage tissues at higher levels
      than in the other tissues examined except liver. Both RBP and PTH/PTHrP inhibited
      the dedifferentiative activity of RA on growth plate chondrocytes when added to
      the culture medium. These results demonstrate that chondrocytes synthesize and
      secrete RBP in vivo and in vitro and suggest that PTH/PTHrP modulates the effect
      of RA by means of RBP production in chondrocytes.

PMID- 10067829
TI  - Pituitary and testicular function in growth hormone receptor gene knockout mice.
AB  - The role of GH in the control of pituitary and testicular function is poorly
      understood. GH receptor gene knockout (GHR-KO) mice were recently produced. As
      these mice are good experimental animals to assess the influence of the effects
      of GH and insulin-like growth factor-I (IGF-I), the present studies were
      undertaken. Young adult male GHR-KO mice and their normal siblings were tested
      for fertility and subsequently injected (i.p.) with saline or GnRH (1 ng/g BW) in
      saline. Fifteen minutes later, blood was obtained via heart puncture. Plasma IGF
      I, PRL, LH, and testosterone concentrations were measured by RIAs. In addition,
      the testicular testosterone response to LH treatment was evaluated in vitro. The
      results indicate that the absence of GH receptors (GHRs) was associated with an
      increase (P < 0.005) in plasma PRL levels, and circulating IGF-I was not
      detectable. Although the basal plasma LH levels were similar in GHR-KO mice
      relative to those in their normal siblings, the circulating LH response to GnRH
      treatment was significantly (P < 0.001) attenuated. Plasma testosterone levels
      were unaffected by disruption of the GHR gene. However, basal (P < 0.01) and LH
      stimulated (P < 0.001) testosterone release from the isolated testes of GHR-KO
      mice were decreased. The rate of fertility in GHR-KO male mice was also reduced.
      These results indicate that the lack of GHRs (with GH resistance and lack of IGF
      I secretion) induces hyperprolactinemia and alters the effect of GnRH on LH
      secretion as well as testicular function. Thus, GH and IGF-I influence pituitary
      and gonadal functions in male mice.

PMID- 10067830
TI  - Insulin-induced up-regulation of lipoprotein lipase messenger ribonucleic acid
      and activity in mammary gland.
AB  - The effects of insulin on lipoprotein lipase (LPL) messenger RNA (mRNA) were
      studied in mammary glands from virgin and late-pregnant rats. Virgin and pregnant
      rats (at 17 days of gestation) were subjected to a continuous infusion (35
      ml/day) with 50% glucose for 72 h to produce a prolonged hyperinsulinemic
      euglycemic condition. Gestation causes a 4-fold increase in LPL mRNA accompanied
      by a 3- to 4-fold increase in total LPL activity. Experimental hyperinsulinemia,
      generated by the 50% glucose infusion, had a similar effect in both pregnant and
      virgin rats, by enhancing (2- to 3-fold) both their LPL activity and LPL mRNA.
      Thus, total LPL activity and LPL mRNA significantly correlated with plasma
      insulin (r = 0.789, P < 0.001; and r = 0.772, P < 0.001, respectively).
      Furthermore, total LPL activity was correlated with LPL mRNA (r = 0.765, P =
      0.001). In conclusion, the present study shows that insulin participates in the
      control of LPL expression in mammary glands, revealing its role as a modulator of
      the enzyme at a mRNA level.

PMID- 10067831
TI  - Regulation of the three-dimensional organization of thyroid epithelial cells into
      follicle structures by the matricellular protein, thrombospondin-1.
AB  - Thyroid epithelial cells in primary culture have the capacity to organize into
      thyroid-specific three-dimensional structures, the follicles, in response to TSH.
      We studied whether thrombospondin 1 (TSP1), which represents, besides
      thyroglobulin, the main protein secreted by thyroid cells, could play a role in
      the process of folliculogenesis. TSH promoted follicle formation and inhibited
      TSP1 production. On the contrary, the phorbol ester, 12-O-tetradecanoyl-phorbol
      13-acetate (1-100 nM) prevented TSH-induced follicle formation and strongly
      increased the synthesis of TSP1. Activation of TSP1 synthesis was dependent upon
      messenger RNA synthesis. Transforming growth factor-beta, like 12-O-tetradecanoyl
      phorbol 13-acetate, increased TSP1 synthesis and prevented TSH-induced follicle
      formation. Thus, signaling molecules that depressed or conversely activated TSP1
      production, respectively promoted or prevented thyroid folliculogenesis. TSP1,
      purified from platelets, was devoid of effect on cell substratum attachment, but
      exerted a concentration-dependent inhibition of the TSH-activated reconstitution
      of thyroid follicles (half-inhibition at 40 microg/ml). TSP1 exhibited the same
      effect when added to thyroid cell aggregates representing primitive follicle
      structures. Our data suggest that the control of thyroid follicle formation may
      operate at least in part through regulation of the production of the
      matricellular protein TSP1, which acts as a negative modulator of the cell-cell
      adhesion process involved in thyroid follicle morphogenesis.

PMID- 10067832
TI  - Regulation of somatotroph differentiation and growth hormone (GH) secretion by
      corticosterone and GH-releasing hormone during embryonic development.
AB  - The role of extracellular factors in the regulation of anterior pituitary cell
      differentiation and GH secretion during embryonic development was investigated.
      Previously, we reported that somatotrophs become a significant population by
      embryonic day (e-) 16 of the chick and that corticosterone is the active compound
      responsible for the observed GH cell-differentiating activity of e-16 serum. More
      recently, the influence of hormone interactions on somatotroph differentiation
      and GH secretion during mid- to late embryogenesis was evaluated. Anterior
      pituitary cells from e-12, -14, and -17 chicks were cultured for 2, 3, and 6 days
      with corticosterone (10(-9) M) and GH-releasing hormone (GHRH; 10(-10)-10(-7) M)
      alone and in combination. Medium samples were analyzed for GH concentrations, and
      recovered cells were subjected to GH reverse hemolytic plaque assay for
      determination of somatotroph percentages and the relative amount of GH secretion
      from individual somatotrophs. GHRH significantly (P < 0.05) increased GH
      secretion from e-17, but not e-12 and e-14, pituitary cells during 2 and 3 days
      of culture. Corticosterone alone failed to increase GH secretion from e-12, -14,
      and -17 pituitary cells; however, corticosterone in combination with GHRH
      increased GH secretion from cells of all three ages. Culture with GHRH decreased
      percentages of e-17 GH-secreting cells in a concentration-dependent manner (from
      basal levels of 12.3 +/- 2.4% to 3.2 +/- 0.7% by 2 days), but did not affect
      percentages of e-12 and e-14 somatotrophs. Conversely, corticosterone increased
      percentages of e-12 and e-14 GH-secreting cells (by as much as 14- and 3-fold
      above basal levels, respectively), but did not alter the proportions of e-17 GH
      cells. Corticosterone in combination with GHRH was more effective than either
      hormone alone for increasing percentages of e-12 GH-secreting cells (from 9.6 +/-
      0.8% with corticosterone to 15.9 +/- 1.5% with corticosterone plus GHRH), but
      this synergistic effect was not apparent until after 3 days of culture. Exposure
      to corticosterone in culture for 2, 3, and 6 days increased subsequent GH release
      from e-12 and e-14 pituitary cells during reverse hemolytic plaque assay.
      Combined treatment with corticosterone and GHRH further increased subsequent GH
      release from e-12 and e-14 cells. We conclude that glucocorticoids induce GH cell
      differentiation and that corticosterone and GHRH can interact at specific stages
      of embryonic development to regulate somatotroph differentiation and GH
      secretion.

PMID- 10067833
TI  - Thyroid hormones act primarily within the brain to promote the seasonal
      inhibition of luteinizing hormone secretion in the ewe.
AB  - In the ewe, thyroid hormones are required for the seasonal suppression of GnRH
      and LH secretion, thereby maintaining an annual rhythm in reproductive activity.
      The primary site of action of thyroid hormones is unknown; in particular, there
      is no evidence to distinguish a central from a peripheral action. In this study,
      we test the hypothesis that thyroid hormones can act directly within the brain to
      promote GnRH/LH seasonal inhibition. Ovariectomized estradiol-treated ewes were
      thyroidectomized late in the breeding season to prevent seasonal LH inhibition.
      T4 was then infused for 3 months, either peripherally or centrally.
      Neuroendocrine reproductive state was monitored by assaying the LH concentration
      in biweekly blood samples. Central infusion of low dose T4, which restored a
      physiological concentration of the hormone in cerebrospinal fluid of these
      thyroidectomized ewes, promoted the neuroendocrine changes that lead to anestrus.
      The serum LH concentration in these animals fell at the same time as the seasonal
      LH decline in euthyroid controls. Neither this same T4 dose infused peripherally
      nor vehicle infused centrally was effective; LH remained elevated, signifying
      blockade of the mechanism for anestrus. Our results provide strong evidence that
      thyroid hormones can act directly within the brain to promote seasonal inhibition
      of neuroendocrine reproductive function in the ewe.

PMID- 10067834
TI  - Intracellular fragments of the natriuretic peptide receptor-C (NPR-C) attenuate
      dopamine efflux.
AB  - Natriuretic peptides suppress adrenergic neurotransmission by a mechanism
      apparently involving the natriuretic peptide receptor-C (NPR-C) rather than
      particulate guanylyl cyclase receptors. The bulk of evidence implicating the NPR
      C in neuromodulatory effects relies on the pharmacological specificity of
      peptides believed to be specific for the NPR-C. This study tests for NPR-C
      effects on neurotransmitter release by examining fragments of the receptor for
      biological activity in pheochromocytoma (PC12) cells permeabilized with
      digitonin. A pentadecapeptide segment of the cytoplasmic portion of the NPR-C
      mimicked the effect of natriuretic peptides to suppress dopamine efflux evoked by
      calcium approximately 40%. Furthermore, an antibody generated against the
      pentadecapeptide fragment abolished the neuromodulatory effect of C-type
      natriuretic peptide in permeabilized cells. In contrast, the carboxy terminal
      nonadecapeptide portion of the NPR-C failed to attenuate dopamine efflux. These
      data are consistent with the proposed role of the NPR-C in transducing the
      biological activity of natriuretic peptides in adrenergic tissue. The most novel
      aspect of these observations involves the potency of the small cytosolic region
      of the NPR-C with the region closest to the membrane accounting for
      neuromodulatory effects.

PMID- 10067835
TI  - Independent signal-transduction pathways for vanadate and for insulin in the
      activation of glycogen synthase and glycogenesis in rat adipocytes.
AB  - The activating effect of vanadate on glycogenesis and on glycogen synthase
      (uridine diphosphate-glucose-glycogen glucosyl transferase) activity was studied
      in rat adipocytes and compared with that of insulin. Using several approaches and
      specific blockers, we found that vanadate and insulin resemble each other, in the
      activation of glycogen synthase, in several aspects: both require nonarrested
      protein phosphatase 1 activity; they are equally suppressed by conditions that
      elevate cAMP-levels; and both depend on the activation of phosphatidylinositol-3
      kinase. The basic differences between them are as follows: 1) vanadate promotes
      glycogenesis through the activation of a cytosolic protein tyrosine kinase, in an
      insulin-receptor-independent manner; 2) vanadate elevates glucose-6-phosphate (G
      6-P) to a higher level than insulin; 3) vanadate-activated glycogenesis is
      accompanied by an increase in the cellular content of immunoreactive glycogen
      synthase, an effect less noticeable with insulin; 4) adipose glucose-6
      phosphatase is inhibited by vanadate (dose for 50% inhibition, IC50 = 7 +/- 0.7
      microM) but not by insulin. We have concluded that insulin and vanadate activate
      glycogenesis through a phosphatidylinositol-3 kinase and dephosphorylation
      dependent mechanism. Vanadate, however, uses a receptor-independent pathway and
      is superior to insulin in elevating the level of G-6-P, a key metabolite for
      activating glycogen synthase. This is attributed to the combined effect of
      vanadate in enhancing glucose entry and in inhibiting dephosphorylation of
      endogenously formed G-6-P. The latter effect is not exerted by insulin.

PMID- 10067836
TI  - Pancreatic glucagon-like peptide-1 receptor couples to multiple G proteins and
      activates mitogen-activated protein kinase pathways in Chinese hamster ovary
      cells.
AB  - Chinese hamster ovary (CHO) cells stably expressing the human insulin receptor
      and the rat glucagon-like peptide-1 (GLP-1) receptor (CHO/GLPR) were used to
      study the functional coupling of the GLP-1 receptor with G proteins and to
      examine the regulation of the mitogen-activated protein (MAP) kinase signaling
      pathway by GLP-1. We showed that ligand activation of GLP-1 receptor led to
      increased incorporation of GTP-azidoanilide into Gs alpha, Gq/11 alpha, and Gi1,2
      alpha, but not Gi3 alpha. GLP-1 increased p38 MAP kinase activity 2.5- and 2.0
      fold over the basal level in both CHO/GLPR cells and rat insulinoma cells (RIN
      1046-38), respectively. Moreover, GLP-1 induced phosphorylation of the immediate
      upstream kinases of p38, MKK3/MKK6, in CHO/GLPR and RIN 1046-38 cells. Ligand
      stimulated GLP-1 receptor produced 1.45- and 2.7-fold increases in tyrosine
      phosphorylation of 42-kDa extracellular signal-regulated kinase (ERK) in CHO/GLPR
      and RIN 1046-38 cells, respectively. In CHO/GLPR cells, these effects of GLP-1 on
      the ERK and p38 MAP kinase pathways were inhibited by pretreatment with cholera
      toxin (CTX), but not with pertussis toxin. The combination of insulin and GLP-1
      resulted in an additive response (1.6-fold over insulin alone) that was
      attenuated by CTX. In contrast, the ability of insulin alone to activate these
      pathways was insensitive to either toxin. Our study indicates a direct coupling
      between the GLP-1 receptor and several G proteins, and that CTX-sensitive
      proteins are required for GLP-1-mediated activation of MAP kinases.

PMID- 10067837
TI  - In vivo insulin signaling in the myocardium of streptozotocin-diabetic rats:
      opposite effects of diabetes on insulin stimulation of glycogen synthase and c
      Fos.
AB  - Diabetes induced by streptozotocin (STZ) in laboratory rats leads to impaired
      glucose metabolism in the heart and changes in myocardial contractile protein
      isoform expression and cardiac function. The purpose of this study was to
      investigate in vivo insulin signaling responses in the myocardium of STZ-diabetic
      rats. Insulin rapidly stimulated tyrosine phosphorylation of the insulin
      receptor, insulin receptor substrate-1 (IRS-1) and, to a lesser extent, IRS-2 in
      normal and diabetic myocardium. In diabetic rats, there was 2-fold higher insulin
      receptor content and insulin-stimulated receptor tyrosine phosphorylation in
      comparison with control rats. IRS-1 tyrosine phosphorylation also increased in
      STZ diabetes in spite of a decrease in IRS-1 content, resulting in a 4-fold
      higher ratio of phosphorylated to total IRS-1. This was associated with 2-fold
      higher IRS-1 precipitable phosphatidylinositide 3-kinase activity in diabetic
      animals. Insulin stimulation of glycogen synthase activity was significantly
      diminished in STZ diabetes, consistent with resistance to insulin in a step
      downstream from phosphatidylinositide 3-kinase activation. Under the same
      experimental conditions, there was a marked increase in insulin stimulation of
      myocardial c-fos messenger RNA content in diabetic animals in comparison with
      controls. These data demonstrate altered early steps in insulin signaling in STZ
      diabetic rat myocardium. Consequent oppositely directed disturbances in growth
      regulatory and glucose regulatory responses to insulin may contribute to the
      development of myocardial functional abnormalities in this model of diabetes.

PMID- 10067838
TI  - Mechanism of hexosamine-induced insulin resistance in transgenic mice
      overexpressing glutamine:fructose-6-phosphate amidotransferase: decreased glucose
      transporter GLUT4 translocation and reversal by treatment with thiazolidinedione.
AB  - Hexosamines have been hypothesized to mediate aspects of glucose sensing and
      toxic effects of hyperglycemia. For example, insulin resistance results when the
      rate-limiting enzyme for hexosamine synthesis, glutamine:fructose-6-phosphate
      amidotransferase (GFA), is overexpressed in muscle and adipose tissue of
      transgenic mice. The glucose infusion rates required to maintain euglycemia at
      insulin infusion rates of 0.5, 2, 15, and 20 mU/kg x min were 39-90% lower in
      such transgenic mice, compared with their control littermates (P < or = 0.01). No
      differences were observed in hepatic glucose output, serum insulin levels, or
      muscle ATP levels. Uptake of 2-deoxyglucose, measured under conditions of
      hyperinsulinemia, was significantly lower in transgenic hindlimb muscle, compared
      with controls (85.9 +/- 17.8 vs. 166.8 +/- 15.1 pmol deoxyglucose/g x min). The
      decrease in glucose uptake by transgenic muscle was associated with a disruption
      in the translocation of the insulin-stimulated glucose transporter GLUT4.
      Fractionation of muscle membranes on a discontinuous sucrose gradient revealed
      that insulin stimulation of control muscle led to a 28.8% increase in GLUT4
      content in the 25% fraction and a 61.2% decrease in the 35% fraction. In
      transgenic muscle, the insulin-stimulated shifts in GLUT4 distribution were
      inhibited by over 70%. Treatment of the transgenic animals with the
      thiazolidinedione troglitazone completely reversed the defect in glucose disposal
      without changing GFA activity or the levels of uridine 5'-diphosphate-N
      acetylglucosamine. Overexpression of GFA in skeletal muscle thus leads to defects
      in glucose transport similar to those seen in type 2 diabetes. These data support
      the hypothesis that excess glucose metabolism through the hexosamine pathway may
      be responsible for the diminished insulin sensitivity and defective glucose
      uptake that are seen with hyperglycemia.

PMID- 10067839
TI  - Stimulation of central and systemic oxytocin release by histamine in the
      paraventricular hypothalamic nucleus: evidence for an interaction with
      norepinephrine.
AB  - Central histaminergic neurons have been implicated in the control of oxytocin
      (OT) secretion in various physiological conditions, including parturition and
      lactation. The present studies investigated whether histamine also influences the
      central intranuclear release of OT, which is known to be important in the
      activation of OT neurons, and the possible interaction of histamine with
      norepinephrine in systemic and central OT release. Microdialysis probes were
      placed immediately adjacent to the hypothalamic paraventricular nucleus (PVN) and
      used for administration of artificial cerebrospinal fluid (ACSF) vehicle, ACSF
      containing histamine, ACSF containing histamine in combination with a specific H1
      or H2 histamine receptor antagonist, or ACSF containing histamine and the alpha
      adrenergic antagonist phentolamine. Dialysates and plasma were collected, and OT
      concentrations were determined using RIA. Dialysis of the PVN with ACSF
      containing histamine significantly increased the release of OT systemically and
      centrally within the PVN. Furthermore, the increases in OT concentration in
      dialysates and plasma were prevented by simultaneous administration of
      chlorpheniramine (an H1 receptor antagonist) or ranitidine (an H2 receptor
      antagonist) as well as by the adrenergic antagonist phentolamine. These data
      demonstrate that histamine acts within the PVN to increase both systemic and
      intranuclear release of OT. Furthermore, the increased OT release induced by
      histamine is dependent upon stimulation of both H1 and H2 histaminergic receptors
      and subsequent activation of alpha-noradrenergic receptors. These findings
      suggest that histamine induces systemic and intranuclear OT release by
      stimulating the release of norepinephrine.

PMID- 10067840
TI  - Characterization of unique truncated prolactin receptor transcripts,
      corresponding to the intracellular domain, in the testis of the sexually mature
      chicken.
AB  - We have examined expression of the chicken PRL receptor (cPRLR) gene in different
      tissues of the chicken by Northern blot analysis. Most tissues examined (ovary,
      testis, oviduct, kidney, and fat) possess a prominent full-length (4.6-kb) cPRLR
      transcript. A larger (11.7-kb) transcript is also detected in ovary, oviduct,
      testis, and kidney after longer exposure. A unique pattern of cPRLR expression
      was found in the testis of sexually mature chickens, which have an unusually high
      abundance of three small transcripts (1.2, 1.7, and 2 kb) in addition to the 4.6
      kb transcript found in other tissues. Three domain-specific complementary DNA
      (cDNA) probes were constructed that correspond to the first and second ligand
      binding regions in the extracellular domain and the transmembrane-intracellular
      domain. With these probes, Northern blot analysis of polyadenylated RNA prepared
      from the testes of a mature (22-week-old) chicken indicates that the highly
      abundant (1.2- and 1.7-kb) and less abundant (2.0-kb) cPRLR transcripts in testis
      hybridize only to the intracellular domain probe. Two types of truncated testis
      specific cPRLR transcripts were identified using 5'-RACE (rapid amplification of
      cDNA ends) analysis of polyadenylated RNA from the testis of a 22-week-old
      chicken. The predominant truncated cDNA sequence contains the highly conserved
      box 1 motif [(+)box 1 cDNA] and diverges (at nucleotide 1396) from that of the
      cPRLR cDNA, just downstream of the transmembrane domain. The other truncated cDNA
      lacks the box 1 motif [(-)box 1 cDNA], which is replaced by 39 bases that could
      encode a hydrophobic N-terminus with a putative 5'-untranslated region of 131
      bases. Young chickens predominately express the full-length cPRLR messenger RNA
      (4.6 kb) in the testis. At the onset of sexual maturity, there is a dramatic
      increase in abundance of the testis-specific (+)box 1 transcript, whereas
      expression of the full-length cPRLR is depressed. The presence of truncated [(+)
      or (-)box 1] cPRLR transcripts in the sexually mature chicken testis suggests a
      complex mechanism of PRL action on gonadal function.

PMID- 10067841
TI  - Central administration of leptin to ovariectomized ewes inhibits food intake
      without affecting the secretion of hormones from the pituitary gland: evidence
      for a dissociation of effects on appetite and neuroendocrine function.
AB  - We have studied the effect of leptin on food intake and neuroendocrine function
      in ovariectomized ewes. Groups (n = 5) received intracerebroventricular infusions
      of either vehicle or leptin (20 microg/h) for 3 days and were blood sampled over
      6 h on days -1, 2, and for 3 h on day 3 relative to the onset of the infusion.
      The animals were then killed to measure hypothalamic neuropeptide Y expression by
      in situ hybridization. Plasma samples were assayed for metabolic parameters and
      pituitary hormones. Food intake was reduced by leptin, but did not change in
      controls. Leptin treatment elevated plasma lactate and nonesterified fatty acids,
      but did not affect glucose or insulin levels, indicating a state of negative
      energy balance that was met by the mobilization of body stores. Pulse analysis
      showed that the secretion of LH and GH was not affected by leptin treatment, nor
      were the mean plasma concentrations of FSH, PRL, or cortisol. Expression of
      messenger RNA for neuropeptide Y in the arcuate nucleus was reduced by the
      infusion of leptin, primarily due to reduced expression per cell rather than a
      reduction in the number of cells observed. Thus, the action of leptin to inhibit
      food intake is dissociated from neuroendocrine function. These results suggest
      that the metabolic effects of leptin are mediated via neuronal systems that
      possess leptin receptors rather than via endocrine effects.

PMID- 10067842
TI  - Possible interactions between gonadotrophs and somatotrophs in the pituitary of
      tilapia: apparent roles for insulin-like growth factor I and estradiol.
AB  - The unique organization of the teleost pituitary, in which cells are grouped
      according to their characteristic hormone, makes this a suitable model for
      studying pituitary paracrine interactions. In a number of fish, including
      tilapia, there are variations in the circulating levels of the gonadotropins and
      GH, which are elevated during the reproductive season, suggesting interactions
      between the reproductive and growth axes. The aim of this study was to
      investigate paracrine interactions between the gonadotrophs and somatotrophs in
      the tilapia pituitary. Initially, dispersed pituitary cells were separated on a
      density gradient in which the gonadotrophs were found in the least dense
      fractions, and the somatotrophs were concentrated in the densest fraction. After
      4 days in culture, cells in the least dense fractions showed characteristic
      cytoplasmic extensions not seen in the somatotrophs, which appeared small and
      failed to form aggregates; somatotrophs were found, however, attached to other
      non-GH cells. Staining of the nuclei with 4,6-diaminidino-2-phenyl
      dihydrochloride revealed that the isolated somatotrophs had undergone nuclear
      condensation and fragmentation typical of apoptosis. Addition of either estradiol
      or human recombinant insulin-like growth factor I (IGF-I; 10 nM) to the
      somatotroph cultures increased the number of cell aggregates and reduced the
      number of condensed or fragmented nuclei. Immunocytochemical studies on pituitary
      sections revealed IGF-I immunoreactivity in regions of the proximal pars distalis
      that stain with gonadotropin IIbeta antisera and also in regions of the rostral
      pars distalis characteristic of corticotrophs; immunoreactive IGF-I was never
      seen in the region of the somatotrophs. Incubation of cells from the different
      fractions with testosterone (10 nM; 24 h) revealed that cells of the least dense
      fractions, which were rich in gonadotrophs, possessed aromatizing ability, which
      was absent in the somatotroph-enriched fraction. These results suggest that
      estradiol and IGF-I, both generated from cells other than the somatotrophs, may
      exert antiapoptotic effects and thus possibly control the size of this population
      of cells.

PMID- 10067843
TI  - 1,25-(OH)2D3 down-regulates expression of Phex, a marker of the mature
      osteoblast.
AB  - Mutations in the PHEX/Phex gene, which encodes for a protein with homology to
      neutral endopeptidases, are responsible for human and murine X-linked
      hypophosphatemia. The present study examined Phex messenger RNA (mRNA) and
      protein expression in cultured osteoblasts and its regulation by 1,25-(OH)2D3.
      Phex mRNA levels were quantitated on Northern blots by densitometric analysis
      relatively to GAPDH mRNA levels. Immunoreactive Phex protein levels were
      evaluated by immunoprecipitation using a polyclonal rabbit antiserum raised
      against a mouse Phex carboxy-terminal peptide. Beta-glycerophosphate-induced
      matrix mineralization in primary osteoblast cultures was associated with
      significant increases in Phex mRNA and protein. Phex mRNA and protein levels were
      low or undetectable in proliferating preosteoblastic MC3T3-E1 cells and
      dramatically increased concomitantly with initiation of matrix mineralization.
      The pattern of Phex expression, however, was similar in nonmineralizing cultures
      grown in the absence of beta-glycerophosphate, indicating that the induction of
      Phex expression in MC3T3-E1 cells was related to cell differentiation rather than
      matrix mineralization. 1,25-(OH)2D3 inhibited mineral deposition and down
      regulated Phex mRNA and protein expression in a time- and dose-dependent manner.
      These results indicate that Phex is a marker of the fully differentiated
      osteoblast and that its expression is stimulated during beta-glycerophosphate
      induced mineralization in primary osteoblast cultures and down-regulated by 1,25
      (OH)2D3, an inhibitor of matrix mineralization. These findings add support for
      Phex having an important role in bone mineralization.

PMID- 10067844
TI  - A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic beta
      cell death.
AB  - Insulin-dependent diabetes mellitus is characterized by the selective destruction
      of pancreatic beta-cells. Chronic treatment with cytokines induced a low voltage
      activated (LVA) Ca2+ current in mouse beta-cells. The concomitant increase in the
      basal cytoplasmic free Ca2+ concentration ([Ca2+]i) was associated with DNA
      fragmentation and cell death. Antagonists of LVA Ca2+ channels prevented this
      elevation of basal [Ca2+]i and DNA fragmentation and reduced the percentage of
      cell death. Exposure to cytokines did not affect the profile of Ca2+ currents or
      basal [Ca2+]i in glucagon-secreting alpha-cells. An increased Ca2+ signal through
      LVA Ca2+ channels may thus be a key feature in cytokine-induced beta-cell
      destruction.

PMID- 10067845
TI  - Induction of androgen receptor by 1alpha,25-dihydroxyvitamin D3 and 9-cis
      retinoic acid in LNCaP human prostate cancer cells.
AB  - We have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits
      proliferation of LNCaP cells, an androgen-responsive human prostate cancer cell
      line. Also, 1,25-(OH)2D3 increases androgen receptor (AR) abundance and enhances
      cellular responses to androgen in these cells. In the current study, we have
      investigated the mechanism by which 1,25-(OH)2D3 regulates AR gene expression and
      the involvement of AR in the 1,25-(OH)2D3- and 9-cis retinoic acid (RA)-mediated
      growth inhibition of LNCaP cells. Northern blot analyses demonstrated that the
      steady-state messenger RNA (mRNA) level of AR was significantly increased by 1,25
      (OH)2D3 in a dose-dependent manner. Time-course experiments revealed that the
      increase of AR mRNA by 1,25-(OH)2D3 exhibited delayed kinetics. In response to
      1,25-(OH)2D3, AR mRNA levels were first detected to rise at 8 h and reached a
      maximal induction of 10-fold over the untreated control at 48 h; the effect was
      sustained at 72 h. Furthermore, the induction of AR mRNA by 1,25-(OH)2D3 was
      completely abolished by incubation of cells with cycloheximide, a protein
      synthesis inhibitor. 1,25-(OH)2D3 was unable to induce expression of an AR
      promoter-luciferase reporter. Together, these findings indicate that the
      stimulatory effect of 1,25-(OH)2D3 on AR gene expression is indirect. Western
      blot analyses showed an increase of AR protein in 1,25-(OH)2D3-treated cells.
      This increased expression of AR was followed by 1,25-(OH)2D3-induced inhibition
      of growth in LNCaP cells. Similar to 1,25-(OH)2D3, 9-cis RA also induced AR mRNA
      expression, and the effect of both hormones was additive. Moreover, 1,25-(OH)2D3
      and 9-cis RA acted synergistically to inhibit LNCaP cell growth. These
      antiproliferative effects of 1,25-(OH)2D3 and 9-cis RA, alone or in combination,
      were blocked by the pure AR antagonist, Casodex. In conclusion, our results
      demonstrate that growth inhibition of LNCaP cells by 1,25-(OH)2D3 and 9-cis RA is
      mediated by an AR-dependent mechanism and preceded by the induction of AR gene
      expression. This finding, that differentiating agents such as vitamin D and A
      derivatives are potent inducers of AR, may have clinical implications in the
      treatment of prostate cancer.

PMID- 10067846
TI  - Acute regulation by corticosteroids of channel-inducing factor gene messenger
      ribonucleic acid in the distal colon.
AB  - The molecular mechanisms by which corticosteroids affect fluid and electrolyte
      balance are unclear. Though glucocorticoid-responsive genes have been identified,
      genes regulated by aldosterone have not. CHIF (channel-inducing factor gene) is a
      recently identified gene that is up-regulated in the distal colon by chronic
      corticosteroid exposure, is expressed in the kidney, and induces a K+-specific
      current in Xenopus oocytes. The predicted protein shows similarity to gammaNa.K
      ATPase, phospholemman, and Mat-8; all seem to be involved in ion transport. CHIF
      thus presents as a potential aldosterone target gene. In this study, CHIF
      expression was examined in rats in the acute timeframe of 0.5-4 h after
      corticosteroid administration. CHIF messenger RNA showed up-regulation by both
      mineralocorticoid and glucocorticoid receptor agonists in the distal colon, which
      was not diminished by cycloheximide. Corticosteroid regulation was not observed
      in the kidney. Basal and induced expression was absent in the lung and in all
      gastrointestinal tissues except colon, with expression increasing proximal to
      distal. CHIF is the first gene to show acute regulation by aldosterone and thus
      encodes a candidate aldosterone-induced protein. In addition, gammaNa.K-ATPase
      gene expression was found to be very low in colon and significantly higher in
      kidney. Regulation by corticosteroids was not evident in either tissue.

PMID- 10067847
TI  - Growth hormone and dexamethasone stimulate lipolysis and activate adenylyl
      cyclase in rat adipocytes by selectively shifting Gi alpha2 to lower density
      membrane fractions.
AB  - GH, in the presence of glucocorticoid, produces a delayed increase in lipolysis
      in rat adipose tissue, but the biochemical mechanisms that account for this
      action have not been established. Other lipolytic agents rapidly activate
      adenylyl cyclase (AC) and the resulting production of cAMP initiates a chain of
      reactions that culminates in the activation of hormone-sensitive lipase. We
      compared responses of segments of rat epididymal fat or isolated adipocytes to 30
      ng/ml GH and 0.1 microg/ml dexamethasone (Dex) with 0.1 ng/ml isoproterenol
      (ISO), which evoked a similar increase in lipolysis. All measurements were made
      during the fourth hour after the addition of GH+Dex or immediately after the
      addition of ISO to cells or tissues that had been preincubated for 3 h without
      hormone. Although no significant increases in cAMP were discernible in
      homogenates of GH+Dex-treated tissues, Rp-cAMPS (Rp-adenosine 3'5'
      phosphothioate), a competitive inhibitor of cAMP, was equally effective in
      decreasing lipolysis induced by GH+Dex or ISO. The proportion of PKA that was
      present in the active form was determined by measuring the incorporation of 32P
      from [gamma-32P]ATP into kemptide in the absence and presence of saturating
      amounts of cAMP. GH+Dex and ISO produced similar increases in protein kinase A
      activity in tissue extracts. Treatment with GH+Dex did not change the total
      forskolin-stimulated AC present in either a crude membrane pellet sedimented at
      16K x g or a less dense membrane pellet sedimented at 100K x g, but doubled the
      AC activity in the 16K pellet when assayed in the absence of forskolin. To
      evaluate possible effects on G proteins, pellets obtained from centrifugation of
      adipocyte homogenates at 16K x g and 100K x g were solubilized and subjected to
      PAGE and Western analysis. GH+Dex decreased Gi alpha2 by 44% (P < 0.02) in the
      16K pellets and increased it by 52% (P < 0.01) in the 100K pellets. Gs alpha in
      the 16K pellet was unaffected by GH+Dex and was decreased (P < 0.05) in the 100K
      pellet. Sucrose density fractionation of the 16K pellets revealed a similar
      GH+Dex-dependent shift of Gi alpha2 to less dense fractions as determined by both
      Western analysis and [32P]NAD ribosylation catalyzed by pertussis toxin. No such
      changes were seen in the distribution of Gs alpha or 5'-nucleotidase. Colchicine
      (100 microM) blocked the GH+Dex-dependent shift of Gi alpha2 from the 16K to the
      100K pellet and blocked the lipolytic effects of GH+Dex, but not those of ISO. We
      conclude that by modifying the relationship between AC and Gi alpha2, GH+Dex
      relieves some inhibition of cAMP production and consequently increases lipolysis.

PMID- 10067848
TI  - Cortisol selectively stimulates pituitary gonadotropin beta-subunit in a
      primitive teleost, Anguilla anguilla.
AB  - It has been suggested that in mammals, glucocorticoids, beside their stress
      related inhibitory effects on reproductive function, may also play a stimulatory
      role at the onset of puberty. Using the juvenile female eel as a model, we
      investigated the potential stimulatory role of cortisol (F) on pituitary
      gonadotropin (GtH-II). GtH-II levels were measured by RIA, and messenger RNA
      (mRNA) levels for alpha- and GtH-II beta-subunits were determined by dot blot
      using homologous probes. F treatment increased eel pituitary GtH-II content in
      vivo and in vitro. Using a long term, serum-free primary culture of pituitary
      cells, we studied the direct effect of F on GtH-II production. F increased the
      GtH-II cellular content in vitro in a dose- and time-dependent manner. The
      relative potencies of various corticosteroids on GtH-II were: triamcinolone
      acetonide > dexamethasone > F >> cortisone and aldosterone, indicating a
      glucocorticoid-specific receptor (GR). F stimulated GtH-II production through a
      selective increase in mRNA levels for GtH-II beta-subunit; no significant effect
      was observed on alpha-subunit mRNA levels. This stimulatory effect of F on GtH-II
      beta, played out directly at the pituitary cell level, recalls that of F on
      FSHbeta in the rat. The present study, performed in a primitive teleost at the
      juvenile stage, suggests that the role of F in the positive regulation of
      gonadotropins at puberty may have arisen early in vertebrate evolution.

PMID- 10067849
TI  - Recombinant growth differentiation factor-9 (GDF-9) enhances growth and
      differentiation of cultured early ovarian follicles.
AB  - Transgenic mice with deletion of the GDF-9 (growth differentiation factor-9) gene
      are characterized by the arrest of ovarian follicle development at the primary
      stage. Based on the hypothesis that GDF-9 is important for early follicle
      development, we isolated rat GDF-9 complementary DNA (cDNA) and generated
      recombinant GDF-9 protein to study its physiological role. Using bacteria-derived
      GDF-9-glutathione S-transferase (GST) fusion protein, specific antibodies to the
      mature form of GDF-9 was generated. Immunohistochemical staining of ovarian
      sections indicated the localization of GDF-9 protein in the oocyte of primary,
      secondary and preantral follicles, whereas immunoblotting demonstrated the
      secretion of GDF-9 by mammalian cells transfected with GDF-9 cDNAs. Recombinant
      GDF-9 was shown to be an N-glycosylated protein capable of stimulating early
      follicle development. Growth of preantral follicles isolated from immature rats
      was enhanced by treatment with either GDF-9 or FSH whereas the combined treatment
      showed an additive effect. In addition, treatment with GDF-9, like forskolin,
      also stimulated inhibin-alpha content in explants of neonatal ovaries. In
      contrast, the stimulatory effects of GDF-9 were not mimicked by amino-terminal
      tagged GDF-9 that was apparently not bioactive. Thus, the present study
      demonstrates the important role of GDF-9 in early follicle growth and
      differentiation. The availability of recombinant bioactive GDF-9 allows future
      studies on the physiological role of GDF-9 in ovarian development in vivo.

PMID- 10067850
TI  - Gender differences in the responsiveness of the sex-dependent isoforms of hepatic
      P450 to the feminine plasma growth hormone profile.
AB  - Most of the constitutive hepatic P450 isoforms expressed in the rat exhibit
      dramatic gender differences. Whereas only male hepatocytes contain CYP2A2, 2C11,
      and 3A2, only female hepatocytes express CYP2C12 and 3- to 4-fold greater levels
      of CYP2C7. This sexually dimorphic expression of hepatic P450 isoforms is
      regulated by the gender-dependent secretory GH profiles, i.e. episodic in males
      and continuous in females. In the case of the feminine GH profile, the continuous
      presence of the hormone in the circulation completely suppresses male-specific
      CYP2A2, 2C11, and 3A2, while stimulating full expression of female-dependent
      CYP2A1, 2C7, 2C12, and non-P450 testosterone 5alpha-reductase (type 1). The
      gender-dependent expression of the P450s can be reversed by exposing male rats to
      the continuous feminine plasma GH profile and females to the episodic masculine
      GH profile. Under these conditions, females will now express the male-specific
      isoforms and suppress the female-dependent forms, whereas the opposite will occur
      in the males. Nevertheless, it is not clear whether the levels of expression or
      suppression are comparable in male and female rats exposed to the same sex
      dependent GH profiles. In the present study, we have renaturalized the
      circulating feminine GH profile in euthyroid-maintained, hypophysectomized female
      and male rats at six concentrations ranging from 3-100% of normal. Continuous
      monitoring of GH levels revealed indistinguishable plasma profiles in females and
      males at each dosage administered. In the case of females, restoration of the
      feminine-like plasma GH profile at a concentration that was 3% of the normal
      level restored expression levels (i.e. mRNA, protein, and/or catalytic activity)
      of female-dependent CYP2C12, 2A1, and 5alpha-reductase to 50% or greater of
      normal and fully suppressed expression of male-specific CYP2A2, 2C11, and 3A2.
      Twice the dosage of the hormone (6% of normal) was required to restore female
      predominant CYP2C7 to 50% of normal in hypophysectomized female rats. In
      contrast, we found that all of the measured isoforms were significantly less
      responsive to the inductive and suppressive effects of the feminine-like GH
      profile when administered to male rats. While suppression of the male-specific
      isoforms (i.e. CYP2A2, 2C11, and 3A2) in male rats required concentrations of GH
      in the feminine profile 2-3 times greater than were effective in female rats, no
      dosage of the hormone was as effective in inducing female-dependent P450s (i.e.
      CYP2A1, 2C7, and 2C12) in males as in females. Clearly, the continuous feminine
      GH profile was more effective at inducing and suppressing gender-dependent
      isoforms of hepatic P450 when restored to female rats, where it is normally
      secreted, than in males. As GH profiles appear to be the sole factor responsible
      for regulating the sexually dimorphic expression of hepatic P450 isoforms in
      adult rats, the differential responsiveness of male and female rats to the
      feminine GH profile are likely to be inherently induced by irreversible
      imprinting during a critical developmental period.

PMID- 10067851
TI  - Increased osteoblastic c-fos expression by parathyroid hormone requires protein
      kinase A phosphorylation of the cyclic adenosine 3',5'-monophosphate response
      element-binding protein at serine 133.
AB  - PTH induces c-fos expression rapidly and transiently in osteoblastic cells and
      requires the activity of the cAMP response element-binding protein (CREB). Here
      we provide evidence that protein kinase A (PKA) is the enzyme responsible for
      phosphorylating CREB at serine 133 (S133) and that this event is required for PTH
      induced c-fos expression. PTH increases the level of phosphorylation of CREB at
      S133 in a time- and dose-dependent manner, correlating with the time and level of
      activation of PKA in response to PTH. PTH-(1-34) and -(1-31), each known to
      activate the cAMP pathway, induced the phosphorylation of CREB and increased the
      levels of c-fos messenger RNA, whereas PTH-(3-34), -(13-34), and -(28-48) could
      not. Specific inhibitors of calcium/calmodulin-dependent protein kinases and
      protein kinase C could not inhibit CREB phosphorylation or c-fos expression in
      response to PTH; however, H-89, a specific inhibitor of PKA, could do so in a
      dose-dependent manner. In addition, PTH-induced c-fos promoter activity was
      completely inhibited in a dose-dependent fashion by transfection of the heat
      stable inhibitor of PKA. Taken together, these data provide strong evidence that
      PKA is the enzyme responsible for phosphorylating CREB at S133 in response to PTH
      and that PKA activity is required for PTH-induced c-fos expression.

PMID- 10067852
TI  - E-box and cyclic adenosine monophosphate response elements are both required for
      follicle-stimulating hormone-induced transferrin promoter activation in Sertoli
      cells.
AB  - Sertoli cells are the epithelial cells responsible for the onset of pubertal
      development and maintenance of spermatogenesis in the adult. Transferrin is one
      of the major secretory products expressed by differentiated Sertoli cells.
      Investigation of the transcriptional control of transferrin gene expression
      provides insight into the regulation of Sertoli cell differentiation. Analysis of
      the mouse transferrin (mTf) promoter reveals the presence of a number of
      conserved response elements that have previously been shown to regulate cell
      specific expression of the human transferrin (hTf) promoter. One of these
      elements is the human PRII region, which is a cAMP response element (CRE)-like
      element that is more than 80% conserved in the mTf promoter. The activation of
      the hTf promoter by FSH and cAMP in rat Sertoli cells has been shown to be
      mediated in part through the CRE-like PRII region and binding of the CRE binding
      protein (CREB). The present study investigates the role of PRII in the activation
      of mTf promoter by FSH and cAMP in rat Sertoli cells. Mutations in the PRII of
      the mTf promoter reduced FSH activation by only 50% and cAMP activation by more
      than 90%. In contrast, the mutant PRII mTf promoter construct was fully activated
      by a partially purified testicular paracrine activity PModS(S300). Gel shift
      experiments demonstrated that proteins that can bind a consensus CRE
      oligonucleotide also bind the PRII region of the mTf promoter. An immunoblot
      confirmed that CREB binds the PRII and promotes the gel shift observed. The
      hypothesis developed was that another cis-acting element in addition to the CRE
      like PRII is also involved in FSH actions. A conserved response element in both
      the mTf and hTf promoters is the basic helix-loop-helix (bHLH) responsive E-box
      sequence. Both FSH and PModS (S300) activity were found to promote a mTf E-box
      gel shift that contained the E2A gene product the bHLH protein E47.
      Interestingly, mutations in the E-box of the mTf promoter completely abolished
      the PModS(S300) activation and partially (52%) inhibited the activation by FSH.
      In contrast, the mutant E-box mTf promoter construct was fully activated by cAMP.
      Finally a double mutation of both the PRII and the E-box completely abolished FSH
      activation of the mTf promoter. These results suggest that optimal activation of
      the mouse transferrin promoter by FSH requires both CREB binding to the CRE-like
      PRII region and bHLH binding to the E-box. Information is provided that indicates
      a number of Sertoli cell promoters contain a close association of E-box and CRE
      like elements. Observations are discussed in regards to the potential
      interactions of the CRE and E-box response elements in mediating FSH actions in
      Sertoli cells.

PMID- 10067853
TI  - Pretranslational regulation of rhythmic type II iodothyronine deiodinase
      expression by beta-adrenergic mechanism in the rat pineal gland.
AB  - It has been demonstrated that type II iodothyronine deiodinase is present in rat
      pineal gland, and the deiodinase activity markedly increases during the hours of
      darkness, primarily through beta-adrenergic mechanism. We have studied the
      relationship between pineal type II iodothyronine deiodinase messenger RNA (mRNA)
      and the deiodinase activity to elucidate the mechanisms involved in the nocturnal
      rise in pineal deiodinase activity. Northern analysis has demonstrated that type
      II iodothyronine deiodinase mRNA is expressed in rat pineal gland, and the mRNA
      markedly increases during the hours of darkness. The nocturnal increase in pineal
      type II iodothyronine deiodinase activity is preceded by the increase in its
      mRNA. Daytime isoproterenol administration resulted in a rapid increase in pineal
      type II iodothyronine deiodinase mRNA followed by the increase in deiodinase
      activity. Propranolol treatment, bilateral superior cervical ganglionectomy, or
      constant light exposure significantly suppressed the nocturnal rise in type II
      iodothyronine deiodinase mRNA as well as the deiodinase activity. Moreover,
      isoproterenol or (Bu)2AMP stimulated type II iodothyronine deiodinase mRNA and
      the deiodinase activity in cultured rat pineal glands. These results suggest that
      the rhythmic change in pineal type II iodothyronine deiodinase activity is
      regulated at least in part at the pretranslational level by a beta-adrenergic
      mechanism transmitted through superior cervical ganglia.

PMID- 10067854
TI  - Regulation of growth hormone secretion by alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid receptors in infantile, prepubertal, and adult male rats.
AB  - Excitatory amino acids, such as glutamate, constitute a major transmitter system
      in the control of hypothalamic-pituitary function. Different subtypes of
      glutamate receptors, such as N-methyl-D-aspartic acid and kainate receptors, have
      been involved in the control of GH secretion. Other excitatory amino acid
      receptor subtypes, as alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA), amino-4-phosphobutyric acid, and metabotropic receptors, have been
      identified, yet their role in the control of neuroendocrine function remains to
      be completely characterized. The purpose of this study was to assess the
      potential involvement of AMPA receptors in the control of GH secretion. In a
      first set of experiments, neonatal (5 and 10 days) and prepubertal (23 days) male
      rats were injected with AMPA (1, 2.5, or 5 mg/kg) or the antagonist of AMPA
      receptors, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide
      (NBQX; 0.25 or 0.50 mg/kg). Serum GH concentrations significantly increased 15
      min after i.p. administration of AMPA in both neonatal and prepubertal male rats.
      In addition, serum GH concentrations decreased after NBQX treatment. The
      stimulatory effect of AMPA was abolished by pretreatment with the blocker of
      nitric oxide synthase, nitro(w)-arginine-methyl ester (40 mg/kg), and was
      partially counteracted by the simultaneous administration of GH-releasing hormone
      (500 microg/kg). Moreover, AMPA was unable to elicit in vitro GH secretion by
      hemipituitaries from prepubertal males, pointing out that the hypothalamus is
      probably the site of action for the reported stimulatory action of AMPA on GH
      release. In a second set of experiments, the effects of AMPA and NBQX were tested
      in adult male rats. As in prepubertal animals, AMPA significantly increased GH
      secretion in adult males, whereas NBQX (20 or 40 nmol), administered through
      intracerebroventricular injection, induced a significant decrease in the
      amplitude of GH pulses. In conclusion, our data indicate that AMPA receptors have
      a physiological stimulatory role in the control of GH secretion in male rats
      throughout the life span. This effect depends on appropriate nitric oxide
      synthesis during the prepubertal age. In addition, AMPA receptors appear to
      modulate pulsatile GH secretion in adulthood.

PMID- 10067855
TI  - A cloned frog vasoactive intestinal polypeptide/pituitary adenylate cyclase
      activating polypeptide receptor exhibits pharmacological and tissue distribution
      characteristics of both VPAC1 and VPAC2 receptors in mammals.
AB  - Three receptor subtypes for the neuropeptides vasoactive intestinal peptide (VIP)
      and pituitary adenylate cyclase-activating polypeptide (PACAP) have been
      identified in mammals: the PAC1 receptor (PAC1-R) which is selectively activated
      by PACAP, and two VPAC receptors (VPAC1-R and VPAC2-R), which are equally
      stimulated by PACAP and VIP. The structures of PACAP and VIP have been well
      conserved during evolution, but little is known about VIP/PACAP receptors in
      nonmammalian species. An amphibian VIP/PACAP receptor complementary DNA (cDNA)
      has been cloned and characterized from a frog (Rana ridibunda) pituitary cDNA
      library. The predicted protein contains seven putative transmembrane domains and
      exhibits the highest sequence identity (65%) with the human VPAC1-R. The cloned
      cDNA was transiently expressed in LLC-PK1 cells, and its pharmacological profile
      was determined in comparison with the human VPAC1-R. Both PACAP and VIP
      stimulated cAMP accumulation through the cloned receptor with an EC50 of about 30
      nM. In contrast, secretin, at concentrations that stimulate the human VPAC1-R,
      had no effect on cAMP production. RT-PCR analysis revealed the widespread
      distribution of this frog VIP/PACAP receptor in peripheral tissues. In situ
      hybridization histochemistry using a complementary RNA probe showed that the
      receptor gene is highly expressed in several hypothalamic and thalamic nuclei and
      to a lesser extent in the pallium and striatum. In the pituitary, the highest
      messenger RNA levels were detected in the distal lobe. Taken together, these data
      show that the cloned frog receptor shares several common features with both the
      VPAC1-R and VPAC2-R of mammals; the frog receptor exhibits the highest sequence
      identity with mammalian VPAC1-R, but the lack of effect of secretin and the brain
      distribution of the receptor are reminiscent of the characteristics of the
      mammalian VPAC2-R. The sequence of the frog receptor should thus prove useful to
      decipher the structure-activity relationships of the VIP/PACAP receptor family.

PMID- 10067856
TI  - Role of signal transduction in internalization of the G protein-coupled receptor
      for parathyroid hormone (PTH) and PTH-related protein.
AB  - For G protein-coupled receptors, limited information is available on the role of
      agonist binding or of the second-messenger products of receptor signaling on
      receptor endocytosis. We explored this problem using the opossum PTH/PTH-related
      protein (PTHrP) receptor, a prototypical Class II G protein-coupled receptor, as
      a model. In one approach, we evaluated the endocytic properties of mutated forms
      of the opossum PTH/PTHrP receptor that we had previously shown to be impaired in
      their ability to initiate agonist-induced signaling when expressed in COS-7
      cells. A point mutation in the third cytoplasmic loop (K382A) that severely
      impairs PTH/PTHrP receptor signaling significantly reduced internalization,
      whereas two mutant receptors that displayed only partial defects in signaling
      were internalized normally. To explore more directly the role of second-messenger
      pathways, we used a cleavable biotinylation method to assess endocytosis of the
      wild-type receptor stably expressed in human embryonic kidney (HEK) 293 cells. A
      low rate of constitutive internalization was detected (<5% over a 30-min
      incubation at 37 C); the rate of receptor internalization was enhanced about 10
      fold by the receptor agonists PTH(1-34) or PTHrP(1-34), whereas the receptor
      antagonist PTH(7-34) had no effect. Forskolin treatment produced a minimal
      increase in constitutive receptor endocytosis, and the protein kinase (PK)-A
      inhibitor H-89 failed to block agonist-stimulated endocytosis. Similarly,
      activation of PK-C, by treatment with phorbol 12-myristate 13-acetate, elicited
      only a minimal increase in constitutive receptor endocytosis; and blockade of the
      PK-C pathway, by treatment with a bisindolylmaleimide, failed to inhibit agonist
      induced receptor endocytosis. Immunofluorescence confocal microscopic studies of
      PTH/PTHrP receptor internalization confirmed the results using receptor
      biotinylation. These findings suggest that: 1) agonist binding is required for
      the efficient endocytosis of the PTH/PTHrP receptor; 2) receptor activation
      (agonist-induced receptor conformational change) and/or coupling to G proteins
      plays a critical role in receptor internalization; and 3) activation of PK-A and
      PK-C is neither necessary nor sufficient for agonist-stimulated receptor
      internalization.

PMID- 10067857
TI  - Human vascular endothelial cells express oxytocin receptors.
AB  - Pharmacological studies in humans and animals suggest the existence of vascular
      endothelial vasopressin (AVP)/oxytocin (OT) receptors that mediate a vasodilatory
      effect. However, the nature of the receptor subtype(s) involved in this
      vasodilatory response remains controversial, and its coupled intracellular
      pathways are unknown. Thus, we set out to determine the type and signaling
      pathways of the AVP/OT receptor(s) expressed in human vascular endothelial cells
      (ECs). Saturation binding experiments with purified membranes of primary cultures
      of ECs from human umbilical vein (HUVEC), aorta (HAEC), and pulmonary artery
      (HPAEC) and [3H]AVP or [3H]OT revealed the existence of specific binding sites
      with a greater affinity for OT than AVP (Kd = 1.75 vs. 16.58 nM). Competition
      binding experiments in intact HUVECs (ECV304 cell line) with the AVP antagonist
      [125I]4-hydroxyphenacetyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2 or the OT
      antagonist [125I]D(CH2)5[O-Me-Tyr-Thr-Orn-Tyr-NH2]vasotocin, and various AVP/OT
      analogs confirmed the existence of a single class of surface receptors of the
      classical OT subtype. RT-PCR experiments with total RNA extracted from HUVEC,
      HAEC, and HPAEC and specific primers for the human V1 vascular, V2 renal, V3
      pituitary, and OT receptors amplified the OT receptor sequence only. No new
      receptor subtype could be amplified when using degenerate primers. DNA sequencing
      of the coding region of the human EC OT receptor revealed a nucleotide sequence
      100% homologous to that of the uterine OT receptor reported previously.
      Stimulation of ECs by OT produced mobilization of intracellular calcium and the
      release of nitric oxide that was prevented by chelation of extra- and
      intracellular calcium. No stimulation of cAMP or PG production was noted.
      Finally, OT stimulation of ECs led to a calcium- and protein kinase C-dependent
      cellular proliferation response. Thus, human vascular ECs express OT receptors
      that are structurally identical to the uterine and mammary OT receptors. These
      endothelial OT receptors produce a calcium-dependent vasodilatory response via
      stimulation of the nitric oxide pathway and have a trophic action.

PMID- 10067858
TI  - Activation of the p38 mitogen-activated protein kinase pathway by gonadotropin
      releasing hormone.
AB  - Previous studies have shown that interaction of GnRH with its serpentine, G
      protein-coupled receptor results in activation of the extracellular signal
      regulated protein kinase (ERK) and the Jun N-terminal protein kinase (JNK)
      pathways in pituitary gonadotropes. In the present study, we examined GnRH
      stimulated activation of an additional member of the mitogen-activated protein
      kinase (MAPK) superfamily, p38 MAPK GnRH treatment of alphaT3-1 cells resulted in
      tyrosine phosphorylation of several intracellular proteins. Separation of
      phosphorylated proteins by ion exchange chromatography suggested that GnRH
      receptor stimulation can activate the p38 MAPK pathway. Immunoprecipitation
      studies using a phospho-tyrosine antibody resulted in increased amounts of
      immunoprecipitable p38 MAPK from alphaT3-1 cells treated with GnRH. Immunoblot
      analysis of whole cell lysates using a phospho-specific antibody directed against
      dual phosphorylated p38 kinase revealed that GnRH-induced phosphorylation of p38
      kinase was dose and time dependent and was correlated with increased p38 kinase
      activity in vitro. Activation of p38 kinase was blocked by chronic phorbol ester
      treatment, which depletes protein kinase C isozymes alpha and epsilon.
      Overexpression of p38 MAPK and an activated form of MAPK kinase 6 resulted in
      activation of c-jun and c-fos reporter genes, but did not alter the expression of
      the glycoprotein hormone alpha-subunit reporter. Inhibition of p38 activity with
      SB203580 resulted in attenuation of GnRH-induced c-fos reporter gene expression,
      but was not sufficient to reduce GnRH-induced c-jun or glycoprotein hormone alpha
      subunit promoter activity. These studies provide evidence that the GnRH signaling
      pathway in alphaT3-1 cells includes protein kinase C-dependent activation of the
      p38 MAPK pathway. GnRH integration of c-fos promoter activity may include
      regulation by p38 MAPK.

PMID- 10067859
TI  - Characterization of insulin-like growth factor binding protein-3 (IGFBP-3)
      binding to human breast cancer cells: kinetics of IGFBP-3 binding and
      identification of receptor binding domain on the IGFBP-3 molecule.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) binds to specific membrane
      proteins located on human breast cancer cells, which may be responsible for
      mediating the IGF-independent growth inhibitory effects of IGFBP-3. In this
      study, we evaluated IGFBP-3 binding sites on breast cancer cell membranes by
      competitive binding studies with IGFBP-1 through -6 and various forms of IGFBP-3,
      including synthetic IGFBP-3 fragments. Scatchard analysis revealed the existence
      of high-affinity sites for IGFBP-3 in estrogen receptor-negative Hs578T human
      breast cancer cells (dissociation constant (Kd) = 8.19 +/- 0.97 x 10(-9) M and
      4.92 +/- 1.51 x 10(5) binding sites/cell) and 30-fold fewer receptors in estrogen
      receptor-positive MCF-7 cells (Kd = 8.49 +/- 0.78 x 10(-9) M and 1.72 +/- 0.31 x
      10(4) binding sites/cell), using a one-site model. These data demonstrate binding
      characteristics of typical receptor-ligand interactions, strongly suggesting an
      IGFBP-3:IGFBP-3 receptor interaction. Among IGFBPs, only IGFBP-5 showed weak
      competition, indicating that IGFBP-3 binding to breast cancer cell surfaces is
      specific and cannot be attributed to nonspecific interaction with
      glycosaminoglycans. This was confirmed by showing that synthetic IGFBP-3 peptides
      containing IGFBP-3 glycosaminoglycan-binding domains competed only weakly for
      IGFBP-3 binding to the cell surface. Rat IGFBP-3 was 20-fold less potent in its
      ability to compete with human IGFBP-3(Echerichia coli), as well as 10- to 20-fold
      less potent for cell growth inhibition than human IGFBP-3, suggesting the
      existence of species specificity in the interaction between IGFBP-3 and the IGFBP
      3 receptor. When various IGFBP-3 fragments were evaluated for affinity for the
      IGFBP-3 receptor, only those fragments that contain the midregion of the IGFBP-3
      molecule were able to inhibit 125I-IGFBP-3(Escherichia coli) binding, indicating
      that the midregion of the IGFBP-3 molecule is responsible for binding to its
      receptor. These observations demonstrate that specific, high-affinity IGFBP-3
      receptors are located on breast cancer cell membranes. These receptors have
      properties that support the notion that they may mediate the IGF-independent
      inhibitory actions of IGFBP-3 in breast cancer cells.

PMID- 10067860
TI  - Cloning, tissue expression, and chromosomal location of the mouse insulin
      receptor substrate 4 gene.
AB  - The insulin receptor substrates (IRSs) are key proteins in signal transduction
      from the insulin receptor. Recently, we discovered a fourth member of this
      family, designated IRS-4, cloned its complementary DNA from the human embryonic
      kidney 293 cell line, and characterized its signaling properties in this cell
      line. As part of an investigation of the physiological role of this IRS, we have
      now cloned the mouse IRS-4 gene and determined its tissue expression and
      chromosomal location. The coding region of the mouse IRS-4 gene contains no
      introns, and in this regard is the same as that of the genes for IRS-1 and -2.
      The predicted amino acid sequence of mouse IRS-4 is highly homologous with that
      of human IRS-4; the pleckstrin homology domain, the phosphotyrosine-binding
      domain, and the tyrosine phosphorylation motifs are especially well conserved.
      The tissue distribution of IRS-4 in the mouse was determined by analysis for the
      expression of its messenger RNA by RT-PCR and for the protein itself by
      immunoprecipitation and immunoblotting. The messenger RNA was detected in
      skeletal muscle, brain, heart, kidney, and liver, but the protein itself was not
      detected in any tissue. These results indicate that IRS-4 is a very rare protein.
      The chromosomal locations of the mouse IRS-4 and IRS-3 genes were determined by
      interspecific back-cross analysis and were found to be on chromosomes X and 5,
      respectively. As the mouse genes for IRS-1 and -2 are on chromosomes 1 and 8,
      respectively, each IRS gene resides on a different chromosome.

PMID- 10067861
TI  - 5'-flanking and intragenic sequences confer androgenic and developmental
      regulation of mouse aldose reductase-like gene in vas deferens and adrenal in
      transgenic mice.
AB  - The MVDP (mouse vas deferens protein) gene, which encodes an aldose reductase
      like enzyme, is mainly expressed in vas deferens epithelium and adrenal cortex.
      Vas deferens MVDP gene transcription was known to be under androgenic control, we
      now have evidence for androgen and probable ACTH responsiveness of the MVDP gene
      in the adrenal. To analyze the role of potential regulatory regions in hormonal,
      developmental, and tissue-specific aspects of MVDP regulation, we generated
      transgenic mice harboring MVDP-CAT fusion genes. The constructs carried either 
      1.8 or -0.5 kb 5'-flanking sequence attached to the chloramphenicol
      acetyltransferase gene in presence or absence of a 3.5-kb intragenic fragment in
      a downstream position. We show that at least two regions ensure proper gene
      regulation in vivo. The first, located within the 1.8-kb promoter fragment,
      directs tissue specificity; positive elements necessary for vas deferens and
      adrenal expression lay within positions -1804 to -510 and -510 to +41,
      respectively. The second, located within the 3.5-kb intragenic fragment spanning
      intron 1 to intron 2, increases percentage of expressing lines and behaves as a
      vas deferens-specific enhancer. Hormonal and developmental control of transgenes
      closely parallel endogenous gene regulation. Androgen and ACTH responsiveness in
      adrenals is conferred by 0.5-kb promoter, whereas in vas deferens, full
      androgenic response of the 1.8-kb promoter required the 3.5-kb intragenic
      fragment. Thus, vas deferens and adrenals use distinct cis-acting elements to
      direct and regulate the expression of the MVDP gene.

PMID- 10067862
TI  - The detrimental effects of spinal cord injury on spermatogenesis in the rat is
      partially reversed by testosterone, but enhanced by follicle-stimulating hormone.
AB  - Our previous studies have demonstrated that impaired spermatogenesis during the
      acute phase of spinal cord injury (SCI) is preceded by a transient (but
      significant) suppression of serum FSH, LH, and testosterone (T) concentrations.
      It is hypothesized that hormonal deprivation may impair Sertoli cell function,
      leading to the loss of spermatogonia, degeneration of spermatogenic cells, and
      eventual regression of the seminiferous epithelium. The current study examined
      the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and
      Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm)
      attenuated some of the spermatogenic lesions and maintained qualitatively
      complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast,
      daily injections of 0.1 U of FSH alone, or in combination with TC implants,
      paradoxically enhanced the regression of spermatogenesis in SCI rats. At this
      time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes
      in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the
      decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further
      enhanced when FSH-treated rats also received TC implants. The intratesticular T
      concentration in untreated and FSH-treated SCI rats was not different from that
      of sham control rats, but it decreased by more than 95% in those SCI rats given
      TC implants alone. These results demonstrate that impairment of spermatogenesis
      during the acute phase of SCI is not related to the availability of FSH and/or T.
      Northern blot analysis revealed an increase in androgen receptor messenger RNA
      (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but
      persisted when FSH was also given. In contrast, the levels of FSH-receptor,
      androgen binding protein, and transferrin mRNA were not affected by SCI but were
      significantly higher in those SCI rats given FSH alone or in combination with TC.
      TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats,
      without concomitant change in those for FSH-receptor and ABP. The changes in
      Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal
      events elicited by these hormones, thus contributing to abnormal epithelial
      environments and regression of spermatogenesis. Maintenance of spermatogenesis in
      SCI rats by exogenous T suggests the feasibility of using exogenous hormones to
      impede the detrimental effects of SCI on spermatogenesis. This approach may have
      clinical applicability for the preservation of spermatogenic functions in SCI
      men.

PMID- 10067863
TI  - ROR alpha augments thyroid hormone receptor-mediated transcriptional activation.
AB  - This study is designed to clarify the role of an orphan nuclear hormone receptor,
      ROR alpha, on thyroid hormone (TH) receptor (TR)-mediated transcription on a TH
      response element (TRE). A transient transfection study using various TREs [i.e.,
      F2 (chick lysozyme TRE), DR4 (direct repeat), and palindrome TRE] and TR and ROR
      alpha1 was performed. When ROR alpha1 and TR were cotransfected into CV1 cells,
      ROR alpha1 enhanced the transactivation by liganded-TR on all TREs tested without
      an effect on basal repression by unliganded TR. By electrophoretic mobility shift
      assay, on the other hand, although ROR alpha bound to all TREs tested as a
      monomer, no (or weak) TR and ROR alpha1 heterodimer formation was observed on
      various TREs except when a putative ROR-response element was present. The
      transactivation by ROR alpha1 on a ROR-response element, which does not contain a
      TRE, was not enhanced by TR. The effect of ROR alpha1 on the TREs is unique,
      because, whereas other nuclear hormone receptors (such as vitamin D receptor) may
      competitively bind to TRE to exert dominant negative function, ROR alpha1
      augmented TR action. These results indicate that ROR alpha1 may modify the effect
      of liganded TR on TH-responsive genes. Because TR and ROR alpha are coexpressed
      in cerebellar Purkinje cells, and perinatal hypothyroid animals and ROR alpha
      disrupted animals show similar abnormalities of this cell type, cross-talk
      between these two receptors may play a critical role in Purkinje cell
      differentiation.

PMID- 10067864
TI  - Regulation of natriuretic peptide receptors by thyrotropin in FRTL-5 rat thyroid
      cells: evidence for nonguanylate cyclase atrial natriuretic factor-binding sites
      in cells lacking the natriuretic peptide receptor C.
AB  - Natriuretic peptide receptors (NPR) are expressed in thyroid-derived cells,
      including the rat FRTL-5 thyroid cell line. We have previously demonstrated that
      atrial natriuretic factor (ANF) binding consistent with the NPR-A receptor is
      significantly increased in FRTL-5 cells cultured in the presence of TSH. The
      purpose of the present study was to determine whether TSH treatment, therefore,
      results in higher levels of ANF-induced intracellular cGMP, and whether TSH
      elicits similar effects on cGMP signaling through the NPR-B receptor. We now show
      that contrary to expectation, long term exposure to 1 mIU/ml bovine TSH (6H
      medium) does not significantly alter maximal ANF-induced cGMP formation.
      Moreover, TSH treatment decreased C-type natriuretic peptide (CNP)-induced cGMP
      generation in FRTL-5 cells, suggesting a down-regulation of NPR-B. A similar
      effect of TSH on ANF- and CNP-induced cGMP was observed in FRTL cells, the
      precursor of the FRTL-5 cell line. Scatchard analysis of [125I]ANF binding in TSH
      treated (6H) FRTL-5 cultures indicated a 5.6-fold increase in high affinity ANF
      binding sites compared with TSH-deficient (5H) cultures [binding capacity (Bmax)
      of 6H cells, 227.2 +/- 33.7 fmol/mg protein; Bmax of 5H cells, 40.2 +/- 4.7
      fmol/mg protein]. The effect of TSH on [125I]ANF binding was mimicked by
      forskolin and (Bu)2cAMP, indicating receptor up-regulation via a cAMP pathway.
      High affinity [125I]CNP-binding sites were present in much lower abundance (Bmax
      of 5H, 0.80 +/- 0.06 fmol/mg protein), and no effect of TSH treatment on them
      could be demonstrated. However, low affinity [125I]CNP binding was increased by
      TSH. RT-PCR confirmed the presence of both NPR-A and NPR-B transcripts in FRTL-5
      cells and showed that TSH treatment significantly decreased NPR-B, but not NPR-A.
      NPR-C transcript was not detectable by RT-PCR in FRTL-5 cells cultured in high
      TSH medium, suggesting that the ANF-binding sites increased by TSH are not NPR-C.
      Both CNP and ANF transcript were also expressed in FRTL-5 cells, and CNP was
      increased by TSH. Together the data support the down-regulation of functional NPR
      B and no change in functional NPR-A by TSH. The vast majority of ANF-binding
      sites in FRTL-5 cells, therefore, are not coupled to cGMP production and may
      represent a novel or altered form of NPR that is regulated by TSH independently
      of NPR-A and NPR-B.

PMID- 10067865
TI  - Photoneural regulation of rat pineal hydroxyindole-O-methyltransferase (HIOMT)
      messenger ribonucleic acid expression: an analysis of its complex relationship
      with HIOMT activity.
AB  - In the pineal gland, synthesis of melatonin requires O-methylation catalyzed by
      hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4). We investigated in vivo
      the molecular mechanisms involved in the regulation of rat pineal HIOMT messenger
      RNA (mRNA) expression and activity using in situ hybridization and radioenzymatic
      assay. HIOMT mRNA levels and activity are both detectable during the daytime and
      display nocturnal increases of 100% and 30%, respectively. These variations are
      controlled by the endogenous clock, as they persist in constant darkness. The
      nocturnal increase in HIOMT mRNA mainly results from a beta-adrenergic
      stimulation of HIOMT gene expression without requiring de novo synthesis of a
      transcription factor. In contrast, the nocturnal increase in HIOMT activity
      appears independent of beta1/alpha1-adrenergic stimulation. A light pulse at
      night abolishes the nighttime increase in HIOMT mRNA, but not HIOMT activity.
      Constant light application for up to 11 days does not depress HIOMT mRNA levels
      lower than the daytime levels, but decreases enzyme activity down to 50% of the
      daytime level. This finding indicates that the nocturnal stimulation of HIOMT
      gene expression is required for sustaining a basal level of activity over a few
      days. Our data suggest 1) that HIOMT gene expression is partly regulated by beta1
      stimulation; and 2) that HIOMT activity is regulated over the short term by a
      nonnoradrenergic stimulus and over the long term by noradrenergic stimulation.

PMID- 10067866
TI  - Raf-1 kinase activation by angiotensin II in adrenal glomerulosa cells: roles of
      Gi, phosphatidylinositol 3-kinase, and Ca2+ influx.
AB  - Little is known of the mechanisms leading to mitogen-activated protein kinase
      (MAPK) activation via Gq-coupled receptors. We therefore examined the pathways by
      which angiotensin II (Ang II) activates Raf-1 kinase, an upstream intermediate in
      the pathway to MAPK, via the Gq-coupled AT1 angiotensin receptor in bovine
      adrenal glomerulosa (BAG) cells. Ang II caused a rapid and transient activation
      of Raf-1 that reached a peak at 5-10 min. Ang II was a potent stimulus of Raf-1
      activation with an ED50 of 10 pM and a maximal response at 1 nM, although higher
      Ang II concentrations elicited a submaximal response. Ang II-stimulated Raf-1
      activity was unaffected by down-regulation of protein kinase C and intracellular
      Ca2+ chelation (using BAPTA) but was partially inhibited by pertussis toxin, and
      was abolished by manumycin A. Removal of extracellular Ca2+ (by EGTA) or blockade
      of L type Ca2+ channels (by nifedipine), as well as inhibition of MEK-1 kinase
      (by PD98059), enhanced Raf-1 activity, whereas wortmannin (100 nM) inhibited
      approximately one half of Ang II-stimulated Raf-1 activity. Hence, Raf-1 kinase
      activation by Ang II in BAG cells is dependent on Ras, is mediated in part via Gi
      and phosphatidylinositol 3-kinase, and is negatively regulated via Ca2+ influx
      and a downstream signaling element(s).

PMID- 10067867
TI  - Regulation and transfer of a murine model of thyrotropin receptor antibody
      mediated Graves' disease.
AB  - In order to replicate a recently described murine model of Graves' disease, we
      immunized AKR/N (H-2k) mice i.p., every 2 weeks, with either a clone of
      fibroblasts expressing both the human TSH receptor (hTSHR) and murine major
      histocompatibility complex (MHC) class II molecules or with fibroblasts
      expressing the MHC class II molecules alone. Mice were bled, and their thyroid
      hormone levels measured, at 6, 12, and up to 18 weeks after the first
      immunization. Between 11-12 weeks after immunization, a significant number of
      mice began to die spontaneously and were found to have developed large goiters.
      Thirty to 40% of mice immunized with hTSHR transfected fibroblasts showed
      markedly increased serum T3 and T4 hormone levels by 12 weeks compared with
      controls, with the highest thyroid hormone levels being T3: 420 ng/dl (normal <
      70) and T4: 16.5 microg/dl (normal < 5). The murine serum demonstrated the
      presence of antibodies to the TSHR, as evidenced by inhibition of labeled TSH
      binding to the hTSHR, and these sera had in vitro thyroid stimulating activity.
      Many of the hyperthyroid mouse exhibited weight loss and hyperactivity and, on
      examination, their thyroids had the histological features of thyroid
      hyperactivity including thyroid enlargement, thyroid cell hypertrophy, and
      colloid droplet formation--all consistent with Graves' disease. In contrast, a
      small number of mice (< 5%) developed hypothyroidism with low serum T4 levels and
      markedly increased TSH concentrations and evidence of thyroid hypoplasia. Both
      hyperthyroidism and hypothyroidism were successfully transferred to naive mice
      using ip cells of immunized mice. Surprisingly, hypothyroidism occurred in many
      recipient mice even after transfer from hyperthyroid donors. These results
      confirmed that immunization with naturally expressed hTSHR in mammalian cells was
      able to induce functional TSHR autoantibodies that either stimulated or blocked
      the mouse thyroid gland and induced hyperthyroidism or thyroid failure.
      Furthermore, both blocking and stimulating antibodies coexisted in the same mice
      as evidenced so clearly by the transfer of hypothyroidism from hyperthyroid mice.
      The addition of a Th2 adjuvant (pertussis toxin) caused approximately 50% of the
      animals to become hyperthyroid beginning early at 9 weeks, whereas a Th1 adjuvant
      (CFA) delayed the disease onset such that only 10% were hyperthyroid by 12 weeks.
      As with human autoimmune thyroid disease, the T cell control of this murine model
      may be critical and requires more extensive investigation.

PMID- 10067868
TI  - Activation of the mitogen-activated protein kinase cascade is necessary but not
      sufficient for basic fibroblast growth factor- and epidermal growth factor
      stimulated expression of endothelial nitric oxide synthase in ovine fetoplacental
      artery endothelial cells.
AB  - Basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and
      vascular endothelial growth factor (VEGF) may play important roles in the
      placental vasculature, not only by controlling cell growth and differentiation,
      but also by mediating production of local vasodilators such as nitric oxide. As
      the mitogen-activated protein kinase (MAPK) signal cascade has been widely
      associated with cell growth in response to growth factors, herein we investigate
      whether bFGF, EGF, and VEGF also stimulate expression of endothelial nitric oxide
      synthase (eNOS) via activation of the MAPK cascade in ovine fetoplacental artery
      endothelial cells. The presence of the receptors for all three growth factors was
      confirmed by both immunocytochemistry and a functional cell proliferation assay.
      All three growth factors at 10 ng/ml rapidly (<10 min) activated MAPK. This
      activation was inhibited by PD 98059, a specific MAPK kinase inhibitor. bFGF and
      EGF, but not VEGF, dose- and time-dependently increased eNOS protein levels.
      Maximal stimulatory effects of bFGF and EGF on eNOS protein expression were
      observed at 10 ng/ml for 24 h of treatment and were associated with elevated eNOS
      messenger RNA. PD 98059 also significantly inhibited bFGF- and EGF-induced
      increases in eNOS protein expression. Because treatment with all three growth
      factors resulted in activation of the MAPK cascade, while bFGF and EGF, but not
      VEGF, increased eNOS expression, we conclude that activation of the MAPK cascade
      is necessary, but not sufficient, for bFGF- and EGF-induced increases in eNOS
      protein expression in ovine fetoplacental artery endothelial cells. Thus,
      additional signaling pathways are implicated in the different controls of eNOS
      expression and mitogenesis by growth factors.

PMID- 10067869
TI  - Characterization of the neuroanatomical distribution of agouti-related protein
      immunoreactivity in the rhesus monkey and the rat.
AB  - Agouti-related protein (AGRP) is a recently described homolog of the skin agouti
      protein. AGRP is transcribed primarily in the adrenal and hypothalamus and is a
      high affinity antagonist of the neural melanocortin-3 and melanocortin-4
      receptors. The perikarya expressing AGRP messenger RNA are found in the arcuate
      nucleus of the rat and rhesus monkey. Using a polyclonal antibody against the
      pharmacologically active domain of AGRP (amino acids 83-132), we have also
      characterized the distribution of AGRP-immunoreactive neurons in both species.
      The major fiber tracts are conserved in both species, with dense projections
      originating in the arcuate nucleus and proceeding along the third ventricle.
      Dense fiber bundles are also visible in the paraventricular, dorsomedial, and
      posterior nuclei in the hypothalamus, in the bed nucleus of the stria terminalis,
      and in the lateral septal nucleus of the septal region. AGRP-containing neurons
      are not visualized in a number of areas, including portions of the amygdala,
      thalamus, and brain stem, that express MC3-R and MC4-R messenger RNA and receive
      innervation from POMC neurons that serve as the source of melanocortin agonists.
      Thus, AGRP is most likely to be involved in modulating a conserved subset of the
      physiological functions of central melanocortin peptides. Based on the particular
      distribution of AGRP neurons, those functions are likely to include the central
      control of energy homeostasis.

PMID- 10067870
TI  - Pituitary homeobox 1 (Ptx1) is differentially expressed during pituitary
      development.
AB  - Pituitary homeobox 1 (Ptx1) is a homeodomain-containing transcription factor
      acting on transcription of all pituitary hormone genes. Its expression is first
      detected in the stomodeal ectoderm and is maintained in all derivatives of this
      structure, including Rathke's pouch. We now show that Ptx1 is expressed in all
      pituitary cells but that it is differentially expressed in different lineages at
      both the messenger RNA and protein levels. On day 12.5 of mouse embryonic
      development, cells expressing the highest levels of Ptx1 are restricted to the
      forming pars tuberalis, also called the rostral tip, a region where the first
      alpha-glycoprotein subunit-expressing cells appear. Coimmunolocalization studies
      reveal that alpha-glycoprotein subunit-positive cells express the highest levels
      of Ptx1 throughout development and in the adult gland. The quantitative
      differences in Ptx1 expression in pituitary cell lineages may relate to a role in
      cell proliferation, lineage commitment, and/or the control of organ development.

PMID- 10067871
TI  - Autocrine regulation of gonadotropin-releasing hormone secretion in cultured
      hypothalamic neurons.
AB  - Episodic hormone secretion is a characteristic feature of the hypothalamo
      pituitary-gonadal system, in which the profile of gonadotropin release from
      pituitary gonadotrophs reflects the pulsatile secretory activity of GnRH
      producing neurons in the hypothalamus. Pulsatile release of GnRH is also evident
      in vitro during perifusion of immortalized GnRH neurons (GT1-7 cells) and
      cultured fetal hypothalamic cells, which continue to produce bioactive GnRH for
      up to 2 months. Such cultures, as well as hypothalamic tissue from adult rats,
      express GnRH receptors as evidenced by the presence of high-affinity GnRH binding
      sites and GnRH receptor transcripts. Furthermore, individual GnRH neurons
      coexpress GnRH and GnRH receptors as revealed by double immunostaining of
      hypothalamic cultures. In static cultures of hypothalamic neurons and GT1-7
      cells, treatment with the GnRH receptor antagonist, [D-pGlu1, D-Phe2, D
      Trp(3,6)]GnRH caused a prominent increase in GnRH release. In perifused
      hypothalamic cells and GT1-7 cells, treatment with the GnRH receptor agonist, des
      Gly10-[D-Ala6]GnRH N-ethylamide, reduced the frequency and increased the
      amplitude of pulsatile GnRH release, as previously observed in GT1-7 cells. In
      contrast, exposure to the GnRH antagonist analogs abolished pulsatile secretion
      and caused a sustained and progressive increase in GnRH release. These findings
      have demonstrated that GnRH receptors are expressed in hypothalamic GnRH neurons,
      and that receptor activation is required for pulsatile GnRH release in vitro. The
      effects of GnRH agonist and antagonist analogs on neuropeptide release are
      consistent with the operation of an ultrashort-loop autocrine feedback mechanism
      that exerts both positive and negative actions that are necessary for the
      integrated control of GnRH secretion from the hypothalamus.

PMID- 10067872
TI  - Pulsatile release of luteinizing hormone-releasing hormone (LHRH) in cultured
      LHRH neurons derived from the embryonic olfactory placode of the rhesus monkey.
AB  - To study the mechanism of LH-releasing hormone (LHRH) pulse generation, the
      olfactory pit/placode and the migratory pathway of LHRH neurons from monkey
      embryos at embryonic age 35-37 were dissected out, under the microscope, and
      cultured on plastic coverslips coated with collagen in a defined medium for 2-5
      weeks. First, we examined whether cultured neurons release the decapeptide into
      media. It was found that LHRH cells release LHRH in a pulsatile manner at
      approximately 50-min intervals. Further, LHRH release was stimulated by
      depolarization with high K+ and the Na+ channel opener, veratridine. However,
      whereas the Na+ channel blocker, tetrodotoxin suppressed the effects of
      veratridine, tetrodotoxin did not alter the effects of high K+. Subsequently, the
      role of extracellular and intracellular Ca2+ in LHRH release was examined. The
      results are summarized as follows: 1) exposing the cells to a low Ca2+ (20 nM)
      buffer solution suppressed LHRH release, whereas exposure to a normal Ca2+
      solution (1.25 mM) maintained pulsatile LHRH release; 2) LHRH release from
      cultured LHRH cells was stimulated by the voltage-sensitive L-type Ca2+ channel
      agonist, Bay K 8644 (10 microM), whereas it was suppressed by the L-type Ca2+
      channel blocker, nifedipine (1 microM), but not by the N-type channel blocker,
      omega-conotoxin GVIA (1 microM); 3) the intracellular Ca2+ stimulant, ryanodine
      (1 microM), stimulated LHRH release, whereas the intracellular Ca2+ transporting
      adenosine triphosphatase antagonist, thapsigargin (1 and 10 microM), did not
      yield consistent results; and 4) carbonyl cyanide p-trifluoromethoxyphenyl
      hydrazone (1 microM), a mitochondrial Ca2+ mobilizer, stimulated LHRH release,
      whereas ruthenium red, a mitochondrial Ca2+ uptake inhibitor, did not induce
      consistent results. These results indicate that: 1) the presence of extracellular
      Ca2+ is essential for LHRH neurosecretion; 2) Ca2+ enters the cell via L-type
      channels but not N-type channels; and 3) mobilization of intracellular Ca2+ from
      inositol 1,4,5-triphosphate-sensitive stores, as well as mitochondrial stores,
      seem to contribute to LHRH release in these cells.

PMID- 10067873
TI  - Regulation of hepatic glycogen in the insulin-like growth factor II-deficient
      mouse.
AB  - Insulin-like growth factor II (IGF-II), a polypeptide hormone with structural
      homologies to insulin-like growth factor I (IGF-I) and insulin, regulates the
      metabolism and growth of many tissues. In this study, we examined the role of IGF
      II in hepatic glycogen metabolism in normal and growth-retarded IGF-II-deficient
      (knockout) mice. Liver glycogen content was significantly lower in the IGF-II
      knockout than in control livers during embryonic day 18 and postnatal day 0.
      Biochemical results were verified histologically using a glycogen-specific stain.
      The enzymatic activity of glycogen synthase, the rate-limiting enzyme for
      glycogen synthesis, was significantly lower in livers of knockout mice than in
      livers from wild-type controls on embryonic day 18 and postnatal day 0. The
      levels of glycogen synthase messenger RNA were not different between the two
      groups at any age studied, indicating that IGF-II acts posttranscriptionally.
      Hepatic glycogen content, measured in newborns after food withdrawal, was
      significantly lower in knockout mice compared with that in wild-type mice after
      0, 3, and 6 h of fasting. Blood glucose was significantly lower in knockouts vs.
      wild-type newborn mice before fasting and was similar in both genotypes after 6 h
      of fasting. Consistent with this, only 23% of IGF-II knockout newborn mice
      survived fasting for 12 h, whereas 93% of wild-type mice survived this treatment.
      These results indicate that IGF-II is required for the regulation of glycogen
      metabolism of the mouse in the perinatal period, possibly via stimulation of
      glycogen synthase activity. IGF-II, via perinatal regulation of glycogen
      synthesis, may regulate fetal growth as well as play an important role in the
      transition from fetal to postnatal life by protecting the neonate against
      hypoglycemia during periods of fasting.

PMID- 10067874
TI  - The novel progesterone receptor antagonists RTI 3021-012 and RTI 3021-022 exhibit
      complex glucocorticoid receptor antagonist activities: implications for the
      development of dissociated antiprogestins.
AB  - We have identified two novel compounds (RTI 3021-012 and RTI 3021-022) that
      demonstrate similar affinities for human progesterone receptor (PR) and display
      equivalent antiprogestenic activity. As with most antiprogestins, such as RU486,
      RTI 3021-012, and RTI 3021-022 also bind to the glucocorticoid receptor (GR) with
      high affinity. Unexpectedly, when compared with RU486, the RTI antagonists
      manifest significantly less GR antagonist activity. This finding indicates that,
      with respect to antiglucocorticoid function, receptor binding affinity is not a
      good predictor of biological activity. We have determined that the lack of a
      clear correlation between the GR binding affinity of the RTI compounds and their
      antagonist activity reflects the unique manner in which they modulate GR
      signaling. Previously, we proposed a two step "active inhibition" model to
      explain steroid receptor antagonism: 1) competitive inhibition of agonist
      binding; and 2) competition of the antagonist bound receptor with that activated
      by agonists for DNA response elements within target gene promoters. Accordingly,
      we observed that RU486, RTI 3021-012, and RTI 3021-022, when assayed for PR
      antagonist activity, accomplished both of these steps. Thus, all three compounds
      are "active antagonists" of PR function. When assayed on GR, however, RU486 alone
      functioned as an active antagonist. RTI 3021-012 and RTI 3021-022, on the other
      hand, functioned solely as "competitive antagonists" since they were capable of
      high affinity GR binding, but the resulting ligand receptor complex was unable to
      bind DNA. These results have important pharmaceutical implications supporting the
      use of mechanism based approaches to identify nuclear receptor modulators. Of
      equal importance, RTI 3021-012 and RTI 3021-022 are two new antiprogestins that
      may have clinical utility and are likely to be useful as research reagents with
      which to separate the effects of antiprogestins and antiglucocorticoids in
      physiological systems.

PMID- 10067875
TI  - Testes exhibit elevated expression of calcitonin gene-related peptide receptor
      component protein.
AB  - Calcitonin gene-related peptide (CGRP) receptor component protein (RCP) is a
      novel protein that modulates CGRP responsiveness in a variety of cell types.
      Using probes based on the isolation of CGRP-RCP complementary DNA (cDNA) from a
      guinea pig organ of Corti cDNA library, we cloned human (h) and mouse (m) CGRP
      RCP cDNAs, both of which encode 148-residue proteins that at the amino acid
      levels are approximately 88% identical to each other and to the 146-residue
      guinea pig CGRP-RCP. Northern blot analysis confirmed the presence of CGRP-RCP
      messenger RNA in all of the human and mouse tissues tested. In these human
      tissues, hCGRP-RCP messenger RNA (major band at approximately 3.1 kb, minor band
      at approximately 7.5 kb) was most prevalent in the testis. In the mouse, the
      highest abundance of CGRP-RCP RNA was clearly in the testis (major band at
      approximately 1.6 kb, minor band at approximately 1.1 kb). Based on this tissue
      distribution of RNA, we sought to identify the cells in the murine testis that
      contained CGRP-RCP protein. Numerous antisera generated against hCGRP-RCP,
      including one to recombinant hCGRP-RCP, exhibited strong immunoreactivity
      localized to the head region of spermatozoa. No CGRP-RCP immunoreactivity was
      observed in other cells at less mature stages of sperm maturation, in Sertoli or
      interstitial (Leydig) cells, or in human spermatozoa. Murine epididymal (mature)
      spermatozoa exhibited CGRP-RCP immunoreactivity identical to that of testicular
      spermatozoa. Spermatozoa that underwent an experimentally induced acrosome
      reaction (acrosomal discharge) lost their CGRP-RCP immunoreactivity. Therefore,
      it appears that CGRP-RCP is associated with the acrosome, suggesting that it may
      play an important role in reproduction.

PMID- 10067876
TI  - Expression and regulation of transcription factors GATA-4 and GATA-6 in
      developing mouse testis.
AB  - Previous studies have shown that transcription factors GATA-4 and GATA-6 are
      expressed in granulosa and thecal cells of the mouse ovary and that GATA-4
      expression in ovarian tissue is regulated by gonadotropins. Given the emerging
      role of GATA-4 and GATA-6 in gonadal cells, we have now studied the expression
      and regulation of these factors in the mouse testis and testicular cell lines. In
      situ hybridization demonstrated GATA-4 messenger RNA (mRNA) in the fetal testis
      at 13.5 days postcoitum. Both GATA-4 and GATA-6 transcripts were observed in late
      fetal, neonatal, juvenile, and adult Sertoli cells. In addition, GATA-4 mRNA was
      detected in interstitial cells throughout development. Immunohistochemistry
      demonstrated GATA-4 protein in both Sertoli and Leydig cells in postnatal
      animals. The regulation of GATA-4 and GATA-6 expression was explored using
      established testicular cell lines. Treatment of Leydig tumor cell lines with hCG
      resulted in a modest, but statistically significant, increase in the steady state
      level of GATA-4 mRNA, comparable to the previously described effect of FSH on
      GATA-4 expression in Sertoli cell lines. Gonadotropin or androgen action was not,
      however, a prerequisite for the basal expression of GATA-4 or GATA-6 in the
      testis, as their presence in Sertoli and Leydig cells was demonstrated in
      genetically hypogonadal hpg mice, in rats treated with GnRH receptor antagonist,
      and in Sertoli cells after chemical abolition of Leydig cells. Cotransfection
      studies using a GATA-4 expression plasmid and an inhibin alpha promoter/reporter
      gene construct in Leydig and granulosa tumor cell lines revealed that the inhibin
      alpha promoter harboring essential GATA-binding sites can be trans-activated by
      GATA-4. In light of these results, we propose that transcription factors GATA-4
      and GATA-6 play differing roles in the maturation and function of testicular
      somatic cells.

PMID- 10067877
TI  - Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid
      dehydrogenase, and androgen receptor in the human prostate by in situ
      hybridization and immunocytochemistry.
AB  - An important source of androgens in the human prostate are those synthesized
      locally from the inactive adrenal precursor dehydroepiandrosterone (DHEA) and its
      sulfated derivative DHEA-S. Three beta-HSD (hydroxysteroid dehydrogenase)
      converts DHEA into androstenedione (4-dione), whereas type 5 17beta-HSD catalyzes
      the reduction of 4-dione into testosterone in the human prostate and other
      peripheral intracrine tissues. In the present study, we have used two
      complementary approaches, namely in situ hybridization and immunocytochemistry,
      to identify the cells that contain the type 5 17beta-HSD messenger RNA and enzyme
      in human benign prostatic hyperplasia (BPH). Localization of 3beta-HSD and of the
      androgen receptor (AR) was also investigated by immunostaining in the same
      tissue. To find out whether there are any differences between BPH and normal
      prostate tissue, the localization of type 5 17beta-HSD was reexamined by
      immunocytochemistry in the normal human prostate samples and also in normal
      prostate epithelial cell line (PrEC). The in situ hybridization results obtained
      with a tritiated uridine triphosphate (3H-UTP)-labeled type 5 17beta-HSD
      riboprobe are in agreement with the immunostaining data obtained with a specific
      antibody to the enzyme. The immunostaining results obtained from normal prostate
      tissue and BPH were found to be similar. Thus, in the glandular epithelium, basal
      cells highly express the messenger RNA and the enzyme, whereas luminal cells show
      a much lower and variable level of expression. In the stroma and walls of blood
      vessels, fibroblasts and the endothelial cells lining the blood vessels show
      positive staining. Similar results are observed when the cellular distribution of
      3beta-HSD is investigated. AR immunoreactivity, however, shows a different
      distribution because, in the epithelium, most of the nuclei of basal cells are
      negative, whereas the majority of nuclei of the luminal cells show positive
      staining. A strong reaction for AR is also found in most stromal cell nuclei and
      in the nuclei of most endothelial cells, as well as in some other cells of the
      walls of blood vessels. In conclusion, human type 5 17beta-HSD, as well as 3beta
      HSD, are highly expressed, not only in the basal epithelial cells and stromal
      fibroblasts but also in the endothelial cells and fibroblasts of the blood
      vessels. AR, on the other hand, is highly expressed in the luminal cells. The
      present data suggest that DHEA is transformed in the basal cells of the glandular
      epithelium into 4-dione by 3beta-HSD and then into testosterone by type 5 17beta
      HSD, whereas dihydrotestosterone is synthesized in the luminal cells after
      diffusion of testosterone from the underlying layer of basal cells. The potential
      role of androgen formation and action in blood vessels is unknown and opens new
      avenues of investigation for a better understanding of the multiple roles of
      androgens.

PMID- 10067878
TI  - Function of stem cell factor as a survival factor of spermatogonia and
      localization of messenger ribonucleic acid in the rat seminiferous epithelium.
AB  - To address the possibility that stem cell factor (SCF) is a paracrine regulator
      of germ cell development in the adult rat testis, stage-specific distribution of
      SCF messenger RNA (mRNA) was investigated with Northern blot and in situ
      hybridization analyses. The highest levels of SCF mRNA were found in stages II-VI
      of the rat seminiferous epithelial cycle, whereas the lowest levels were in
      stages VII-VIII. Intermediate levels of SCF mRNA were detected in stages IX-XIV-I
      of the cycle. The expression of the SCF gene was found to be developmentally
      regulated, and the expression pattern followed the process of Sertoli cell
      proliferation and differentiation during postnatal life. The effect of mouse
      recombinant SCF on spermatogonial DNA synthesis was studied using an in vitro
      tissue culture system for stage-defined seminiferous tubules. A significant
      increase in DNA synthesis in spermatogonia could be detected when tubule segments
      from stage XII were cultured in the presence of 100 ng/ml SCF for 48 h (P < 0.05)
      and 72 h (P < 0.01). This observation was further confirmed with autoradiographic
      analyses; almost a 100-fold increase in thymidine incorporation in the SCF
      treated (100 ng/ml) tubule segments was observed compared with that in untreated
      samples. The results of the present study suggest that SCF is a Sertoli cell
      produced paracrine regulator and acts as a survival factor for spermatogonia in
      the adult rat seminiferous epithelium in a stage-specific manner.

PMID- 10067879
TI  - Stage-specific regulation of stem cell factor gene expression in the rat
      seminiferous epithelium.
AB  - To assess the regulation of stem factor factor (SCF) gene expression during
      spermatogenesis, we tested the effects of hormones (FSH, testosterone, and 17beta
      estradiol) and some growth factors [transforming growth factor-beta (TGF beta),
      TGF alpha, tumor necrosis factor-alpha, and activin] on SCF gene expression by
      using a transillumination-assisted microdisection technique, a seminiferous
      tubule culture system, and Northern hybridization. Our results showed that FSH
      (10 ng/ml) increased steady state levels of SCF messenger RNA (mRNA) in a stage
      specific and time-dependent manner. 8-Bromo-cAMP could increase the SCF mRNA
      level in a similar way as FSH, whereas phorbol 12-myristate 13-acetate had no
      effect. Actinomycin D could abolish the stimulatory effect of FSH, whereas
      cyclohexamide could not. The half-life of SCF mRNA was apparently prolonged after
      FSH stimulation (FSH-treated tubules, 15.6 +/- 1.2 h; controls, 8.6 +/- 2.7 h).
      Nuclear run-on assay revealed 5- and 10-fold increases in the transcription rate
      after FSH stimulation for 8 and 30 h, respectively. Neither testosterone nor
      estradiol had significant effects on SCF gene expression in our tissue culture
      system. Activin, TGF beta, TGF alpha, and tumor necrosis factor-alpha had no
      effect on SCF gene expression in vitro. In conclusion, SCF gene expression in the
      rat seminiferous tubule is regulated by FSH through the cAMP/protein kinase A
      pathway. FSH regulates SCF gene expression at both transcriptional and
      posttranscriptional levels involving the increase in transcription rate and
      prolongation of half-life of SCF mRNA, but is independent of de novo protein
      synthesis.

PMID- 10067880
TI  - Former Pasteur head defends politicians.

PMID- 10067881
TI  - US groups sue over approval of Bt crops...as UK press reports come under fire.

PMID- 10067882
TI  - Spain makes transgenic crop producers pay into insurance fund.

PMID- 10067883
TI  - Congress may block stem-cell research.

PMID- 10067884
TI  - How hunger keeps the population down.

PMID- 10067885
TI  - Revolutionary ideas come round again.

PMID- 10067886
TI  - Hox proteins reach out round DNA.

PMID- 10067887
TI  - Bioenergetics. One price to run, swim or fly?

PMID- 10067888
TI  - Sorting out the neuron.

PMID- 10067889
TI  - RNA splicing. Running rings around RNA.

PMID- 10067890
TI  - Breathing through skin in a newborn mammal.

PMID- 10067891
TI  - The bio-logic of facial geometry.

PMID- 10067892
TI  - A ferric-chelate reductase for iron uptake from soils.
AB  - Iron deficiency afflicts more than three billion people worldwide, and plants are
      the principal source of iron in most diets. Low availability of iron often limits
      plant growth because iron forms insoluble ferric oxides, leaving only a small,
      organically complexed fraction in soil solutions. The enzyme ferric-chelate
      reductase is required for most plants to acquire soluble iron. Here we report the
      isolation of the FRO2 gene, which is expressed in iron-deficient roots of
      Arabidopsis. FRO2 belongs to a superfamily of flavocytochromes that transport
      electrons across membranes. It possesses intramembranous binding sites for haem
      and cytoplasmic binding sites for nucleotide cofactors that donate and transfer
      electrons. We show that FRO2 is allelic to the frd1 mutations that impair the
      activity of ferric-chelate reductase. There is a nonsense mutation within the
      first exon of FRO2 in frd1-1 and a missense mutation within FRO2 in frd1-3.
      Introduction of functional FRO2 complements the frd1-1 phenotype in transgenic
      plants. The isolation of FRO2 has implications for the generation of crops with
      improved nutritional quality and increased growth in iron-deficient soils.

PMID- 10067893
TI  - A diffusion barrier maintains distribution of membrane proteins in polarized
      neurons.
AB  - The asymmetric distribution of proteins to distinct domains in the plasma
      membrane is crucial to the function of many polarized cells. In epithelia,
      distinct apical and basolateral surfaces are maintained by tight junctions that
      prevent diffusion of proteins and lipids between the two domains. Polarized
      neurons maintain axonal and somatodendritic plasma membrane domains without an
      obvious physical barrier. Indeed, the artificial lipid Dil encounters no
      diffusion barrier at the presumptive domain boundary, the axon hillock. By
      measuring the lateral mobility of membrane proteins using optical tweezers, we
      show here that some membrane proteins exhibit markedly reduced mobility in the
      initial segment of the axon. Disruption of F-actin and low levels of dimethyl
      sulphoxide (DMSO) abolish this diffusion barrier and lead to redistribution of
      membrane markers that had previously been polarized. Immobilization in the
      initial segment may reflect, at least in part, differential tethering to
      cytoskeletal components. Therefore, the ability to maintain a polarized
      distribution of membrane proteins depends on a specialized domain at the initial
      segment of the axon, which restricts lateral mobility and serves as a new type of
      diffusion barrier that acts in the absence of cell-cell contact.

PMID- 10067894
TI  - Development of peripheral lymphoid organs and natural killer cells depends on the
      helix-loop-helix inhibitor Id2.
AB  - Transcription factors with a basic helix-loop-helix (HLH) motif have been shown
      to be crucial for various cell differentiation processes during development of
      multicellular organisms. Id proteins inhibit the functions of these transcription
      factors in a dominant-negative manner by suppressing their heterodimerization
      partners through the HLH domains. Members of the Id family also promote cell
      proliferation, implying a role in the control of cell differentiation. Here we
      show that Id2 is indispensable for normal development of mice. Id2-/- mice lack
      lymph nodes and Peyer's patches. However, their splenic architecture is normal,
      exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell
      population that produces lymphotoxins, essential factors for the development of
      secondary lymphoid organs, is barely detectable in the Id2-/- intestine.
      Furthermore, the null mutants show a greatly reduced population of natural killer
      (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our
      results indicate that Id2 has an essential role in the generation of peripheral
      lymphoid organs and NK cells.

PMID- 10067895
TI  - The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt
      signals.
AB  - Embryological and genetic evidence indicates that the vertebrate head is induced
      by a different set of signals from those that organize trunk-tail development.
      The gene cerberus encodes a secreted protein that is expressed in anterior
      endoderm and has the unique property of inducing ectopic heads in the absence of
      trunk structures. Here we show that the cerberus protein functions as a
      multivalent growth-factor antagonist in the extracellular space: it binds to
      Nodal, BMP and Wnt proteins via independent sites. The expression of cerberus
      during gastrulation is activated by earlier nodal-related signals in endoderm and
      by Spemann-organizer factors that repress signalling by BMP and Wnt. In order for
      the head territory to form, we propose that signals involved in trunk
      development, such as those involving BMP, Wnt and Nodal proteins, must be
      inhibited in rostral regions.

PMID- 10067896
TI  - Inhibition of transforming growth factor-beta/SMAD signalling by the interferon
      gamma/STAT pathway.
AB  - Transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) have
      opposite effects on diverse cellular functions, but the basis for this antagonism
      is not known. TGF-beta signals through a receptor serine kinase that
      phosphorylates and activates the transcription factors Smads 2 and 3, whereas the
      IFN-gamma receptor and its associated protein tyrosine kinase Jak1 mediate
      phosphorylation and activation of the transcription factor Stat1. Here we present
      a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits
      the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely,
      the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus,
      and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1,
      IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents
      the interaction of Smad3 with the TGF-beta receptor. The results indicate a
      mechanism of transmodulation between the STAT and SMAD signal-transduction
      pathways.

PMID- 10067897
TI  - Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex.
AB  - During the development of multicellular organisms, gene expression must be
      tightly regulated, both spatially and temporally. One set of transcription
      factors that are important in animal development is encoded by the homeotic (Hox)
      genes, which govern the choice between alternative developmental pathways along
      the anterior-posterior axis. Hox proteins, such as Drosophila Ultrabithorax, have
      low DNA-binding specificity by themselves but gain affinity and specificity when
      they bind together with the homeoprotein Extradenticle (or Pbxl in mammals). To
      understand the structural basis of Hox-Extradenticle pairing, we determine here
      the crystal structure of an Ultrabithorax-Extradenticle-DNA complex at 2.4 A
      resolution, using the minimal polypeptides that form a cooperative heterodimer.
      The Ultrabithorax and Extradenticle homeodomains bind opposite faces of the DNA,
      with their DNA-recognition helices almost touching each other. However, most of
      the cooperative interactions arise from the YPWM amino-acid motif of
      Ultrabithorax-located amino-terminally to its homeodomain-which forms a reverse
      turn and inserts into a hydrophobic pocket on the Extradenticle homeodomain
      surface. Together, these protein-DNA and protein-protein interactions define the
      general principles by which homeotic proteins interact with Extradenticle (or
      Pbx1) to affect development along the anterior-posterior axis of animals.

PMID- 10067898
TI  - What can we infer from author order in epidemiology?

PMID- 10067899
TI  - Recurrence in affective disorder: analyses with frailty models.
AB  - The risk of recurrence in affective disorder is influenced by the number of prior
      episodes and by a person's tendency toward recurrence. Newly developed frailty
      models were used to estimate the effect of the number of episodes on the rate of
      recurrence, taking into account individual frailty toward recurrence. The study
      base was the Danish psychiatric case register of all hospital admissions for
      primary affective disorder in Denmark during 1971-1993. A total of 20,350 first
      admission patients were discharged with a diagnosis of major affective disorder.
      For women with unipolar disorder and for all kinds of patients with bipolar
      disorder, the rate of recurrence was affected by the number of prior episodes
      even when the effect was adjusted for individual frailty toward recurrence. No
      effect of episodes but a large effect of the frailty parameter was found for
      unipolar men. The authors concluded that the risk of recurrence seems to increase
      with the number of episodes of bipolar affective disorder in general and for
      women with unipolar disorder.

PMID- 10067900
TI  - Familial aggregation of blood pressure in a rural Chinese community.
AB  - This study investigated blood pressure in 1,183 Chinese nuclear families (mother,
      father, and first two children) via a cross-sectional 1994-1997 survey. The
      mother's, the father's, and the first sibling's blood pressures were each
      significantly and independently related to the second sibling's blood pressure
      after adjustment for sex, age, height, weight, education, smoking, and alcohol
      consumption. The association was consistent across the four age strata (6-10, 11
      14, 15-19, and > or = 20 years). The rate of high systolic blood pressure in the
      second sibling was lowest (2.3%) when both parents and the first sibling were in
      the low blood pressure tertile (low-low group) and highest (26.0%) when these
      family members were in the high blood pressure tertile (high-high group). The
      rate was intermediate if only the parents (10.7%, high-low group) or the first
      sibling (8.4%, low-high group) was in the high blood pressure tertile. As
      compared with the low-low group, the odds ratios for the high-high, high-low, and
      low-high groups were 14.3 (95% confidence interval 4.3-48.2), 4.3 (95% confidence
      interval 1.2-15.6), and 3.9 (95% confidence interval 1.1-14.4), respectively. A
      similar pattern was found for diastolic blood pressure. The data indicate a
      strong familial aggregation of blood pressure in this population and show that
      such a familial influence on blood pressure can be detected from early childhood
      onward.

PMID- 10067901
TI  - Dietary iron and risk of myocardial infarction in the Rotterdam Study.
AB  - Free iron has been implicated in lipid peroxidation and ischemic myocardial
      damage, and it has been suggested that iron is an independent risk factor for
      myocardial infarction. The authors investigated whether dietary iron is
      associated with an increased risk of fatal and nonfatal myocardial infarction in
      the Rotterdam Study, a community-based prospective cohort study of 7,983 elderly
      subjects in Rotterdam, the Netherlands. The study sample consisted of 4,802
      participants who at baseline had no known history of myocardial infarction and
      for whom dietary data were available. From 1990 to 1996, 124 subjects had a
      myocardial infarction. No association was observed between total iron intake and
      risk of myocardial infarction after adjustment for age and sex (relative risk for
      the highest vs. the lowest tertile of intake = 0.89, 95% confidence interval (CI)
      0.55-1.45, p for trend = 0.640). Heme iron intake was positively associated with
      risk of myocardial infarction (relative risk for the highest vs. the lowest
      tertile of intake = 1.83, 95% CI 1.16-2.91, p for trend = 0.008) after adjustment
      for age and sex, and this association persisted after multivariate adjustment
      (relative risk = 1.86, 95% CI 1.14-3.09, p for trend = 0.010). A distinction
      between fatal and nonfatal cases of myocardial infarction indicated that the
      association of heme iron with myocardial infarction was more pronounced in fatal
      cases. The results suggest that a high dietary heme iron intake is related to an
      increased risk of myocardial infarction and that it may specifically affect the
      rate of fatality from myocardial infarction.

PMID- 10067902
TI  - Variability in meta-analytic results concerning the value of cholesterol
      reduction in coronary heart disease: a meta-meta-analysis.
AB  - Despite official support for the efficacy of cholesterol reduction, considerable
      controversy exists, and meta-analyses of this topic have produced conflicting
      results. The authors assessed the variability of meta-analyses, evaluating the
      cardiovascular value of cholesterol reduction while attempting to explain the
      variability. Metaanalyses were identified by electronic search and citation
      tracking. Included were those conducted prior to 1995 that dealt with cholesterol
      reduction and total mortality, cardiovascular mortality, or nonfatal
      cardiovascular disease. In addition to extracting odds ratios for total
      mortality, cardiovascular mortality, and nonfatal cardiovascular disease, the
      authors encoded methodological variables, publication variables, and data
      concerning investigators' backgrounds. Twenty-three meta-analyses were reviewed,
      and 15 concluded that cholesterol reduction was beneficial. Summary odds ratios
      for total mortality were heterogeneous, generally failing to support the value of
      cholesterol reduction. Odds ratios depended on inclusion criteria and
      investigator variables. Odds ratios for cardiovascular mortality and for nonfatal
      cardiovascular disease were more homogeneous and supported the value of
      cholesterol reduction. Methodologically better meta-analyses tended to report
      more beneficial odds ratios. Although "supportiveness" of the value of
      cholesterol reduction was associated with inclusion/exclusion criteria and
      publication variables, the primary outcome variable related to supportiveness was
      the statistical significance of the odds ratios for cardiovascular mortality.

PMID- 10067903
TI  - Maternal smoking and Down syndrome: the confounding effect of maternal age.
AB  - Inconsistent results have been reported from studies evaluating the association
      of maternal smoking with birth of a Down syndrome child. Control of known risk
      factors, particularly maternal age, has also varied across studies. By using a
      population-based case-control design (775 Down syndrome cases and 7,750 normal
      controls) and Washington State birth record data for 1984-1994, the authors
      examined this hypothesized association and found a crude odds ratio of 0.80 (95%
      confidence interval 0.65-0.98). Controlling for broad categories of maternal age
      (<35 years, > or =35 years), as described in prior studies, resulted in a
      negative association (odds ratio = 0.87, 95% confidence interval 0.71-1.07).
      However, controlling for exact year of maternal age in conjunction with race and
      parity resulted in no association (odds ratio = 1.00, 95% confidence interval
      0.82-1.24). In this study, the prevalence of Down syndrome births increased with
      increasing maternal age, whereas among controls the reported prevalence of
      smoking during pregnancy decreased with increasing maternal age. There is a
      substantial potential for residual confounding by maternal age in studies of
      maternal smoking and Down syndrome. After adequately controlling for maternal age
      in this study, the authors found no clear relation between maternal smoking and
      the risk of Down syndrome.

PMID- 10067904
TI  - Low-weight neonatal survival paradox in the Czech Republic.
AB  - Analysis of vital statistics for the Czech Republic between 1986 and 1993,
      including 3,254 infant deaths from 350,978 first births to married and single
      women who conceived at ages 18-29 years, revealed a neonatal survival advantage
      for low-weight infants born to disadvantaged (single, less educated) women,
      particularly for deaths from congenital anomalies. This advantage largely
      disappeared after the neonatal period. The same patterns have been observed for
      low-weight infants born to black women in the United States. Since the Czech
      Republic had an ethnically homogenous population, virtually universal prenatal
      care, and uniform institutional conditions for delivery, Czech results must be
      attributed to social rather than to biologic or medical circumstances. This
      strengthens the contention that in the United States, the black neonatal survival
      paradox may be due as much to race-related social stigmatization and consequent
      disadvantage as to any hypothesized hereditary influences on birth-weight
      specific survival.

PMID- 10067905
TI  - Influence of a family history of cancer within and across multiple sites on
      patterns of cancer mortality risk for women.
AB  - A case-control study nested within a large cohort, the American Cancer Society
      Cancer Prevention Study-1, was conducted to test associations between a family
      history of cancer and cancer mortality in women. By using logistic regression,
      the authors analyzed family history, as reported by 429,483 women enrolled in
      1959, relative to subsequent mortality through 1972 from cancer within and across
      multiple sites. The associations between family history and cancer mortality were
      generally stronger within cancer sites than across cancer sites. Within-site
      associations were found for breast cancer (odds ratio (OR) = 1.9), colorectal
      cancer (OR = 1.6), stomach cancer (OR = 1.9), and lung cancer (OR = 1.7). Across
      site associations were observed for a family history of 1) breast cancer as a
      risk factor for ovarian cancer mortality (OR = 1.6), 2) stomach cancer as a risk
      factor for ovarian cancer mortality (OR = 1.5), and 3) uterine cancer as a risk
      factor for pancreatic cancer mortality (OR = 1.6). A general pattern of positive
      associations was observed between a family history of cancer at several sites and
      subsequent death from pancreatic cancer. These findings support the growing body
      of evidence from cancer genetics suggesting that inherited cancer-susceptibility
      genes increase the risk for cancer at many sites and are not specific to cancer
      risk within a single site.

PMID- 10067906
TI  - Alcohol intake and the risk of lung cancer: influence of type of alcoholic
      beverage.
AB  - Alcohol consumption has been associated with an increased risk of lung cancer,
      but the antioxidants in wine may, in theory, provide protection. This association
      was studied in 28,160 men and women subjects from three prospective studies
      conducted in 1964-1992 in Copenhagen, Denmark. After adjustment for age, smoking,
      and education, a low to moderate alcohol intake (1-20 drinks per week) was not
      associated with an increased risk of lung cancer. Men who consumed 21-41 and more
      than 41 drinks per week had relative risks of 1.23 (95% confidence interval (CI)
      0.88-1.74) and 1.57 (95% CI 1.06-2.33), respectively. The risk of lung cancer
      differed according to the type of alcohol consumed: After abstainers were
      excluded, drinkers of 1-13 and more than 13 glasses of wine per week had relative
      risks of 0.78 (95% CI 0.63-0.97) and 0.44 (95% CI 0.22-0.86), respectively, as
      compared with nondrinkers of wine (p for trend = 0.002). Corresponding relative
      risks for beer intake were 1.09 (95% CI 0.83-1.43) and 1.36 (95% CI 1.02-1.82),
      respectively (p for trend = 0.01); for spirits, they were 1.21 (95% CI 0.97-1.50)
      and 1.46 (95% CI 0.99-2.14), respectively (p for trend = 0.02). In women, the
      ability to detect associations with high alcohol intake and type of beverage was
      limited because of a limited range of alcohol intake. The authors concluded that
      in men, a high consumption of beer and spirits is associated with an increased
      risk of lung cancer, whereas wine intake may protect against the development of
      lung cancer.

PMID- 10067907
TI  - Association between serum fructosamine and mortality in elderly women: the study
      of osteoporotic fractures.
AB  - Serum fructosamine levels can be used to estimate long-term serum glucose values
      and can be measured in frozen serum. The authors examined whether fructosamine
      levels were associated with mortality in a cohort of 9,704 white women (> or = 65
      years of age) recruited from September 1986 to October 1988 at four clinical
      centers in the United States. A random sample of women who had died during a mean
      of 6 years of follow-up (n = 55) was compared with randomly selected controls (n
      = 276, 54 of whom had died). Fructosamine assays were performed blinded to vital
      status. Hazard ratios with 95% confidence intervals were adjusted for age,
      clinical center, smoking, hypertension, and serum albumin and cholesterol levels.
      Each standard deviation (46 micromol) increase in fructosamine level was
      associated with a 1.3-fold (95% confidence interval (CI) 1.0-1.6, p = 0.04)
      increased rate of all-cause mortality, including a 1.5-fold (95% CI 1.0-2.1, p =
      0.03) increase in cardiovascular disease mortality. Elevated fructosamine levels
      (>285 micromol/liter) were associated with a 4.3-fold (95% CI 1.6-12, p = 0.004)
      increased rate of cardiovascular mortality; in women without a history of
      diabetes, the hazard ratio was 4.6 (95% CI 1.3-16, p = 0.02). Fructosamine level,
      or another indicator of glycemia, should be included when the risk of
      cardiovascular disease among older patients is evaluated.

PMID- 10067908
TI  - Prospective cohort study of antioxidant vitamin supplement use and the risk of
      age-related maculopathy.
AB  - In a prospective cohort study, the authors examined whether self-selection for
      antioxidant vitamin supplement use affects the incidence of age-related
      maculopathy. The study population consisted of 21,120 US male physician
      participants in the Physicians' Health Study I who did not have a diagnosis of
      age-related maculopathy at baseline (1982). During an average of 12.5 person
      years of follow-up, a total of 279 incident cases of age-related maculopathy with
      vision loss to 20/30 or worse were confirmed by medical record review. In
      multivariate analysis, as compared with nonusers of supplements, persons who used
      vitamin E supplements had a possible but nonsignificant 13% reduced risk of age
      related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI)
      0.53-1.43), while users of multivitamins had a possible but nonsignificant 10%
      reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C
      supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational
      data suggest that among persons who self-select for supplemental use of
      antioxidant vitamin C or E or multivitamins, large reductions in the risk of age
      related maculopathy are unlikely. Randomized trial data are accumulating to
      enable reliable detection of the existence of more plausible small-to-moderate
      benefits of these agents alone and in combination on age-related maculopathy.

PMID- 10067909
TI  - Re: "The failure of academic epidemiology: witness for the prosecution".

PMID- 10067910
TI  - Re: The absence of reports relating dairy food to mortality.

PMID- 10067911
TI  - Clinical variability in patients with Apert's syndrome.
AB  - OBJECT: Apert's syndrome is characterized by faciocraniosynostosis and severe
      bony and cutaneous syndactyly of all four limbs. The molecular basis for this
      syndrome appears remarkably specific: two adjacent amino acid substitutions
      (either S252W or P253R) occurring in the linking region between the second and
      third immunoglobulin domains of the fibroblast growth factor receptor (FGFR)2
      gene. The goal of this study was to examine the phenotype/genotype correlations
      in patients with Apert's syndrome. METHODS: In the present study, 36 patients
      with Apert's syndrome were screened for genetic mutations. Mutations were
      detected in all cases. In one of the patients there was a rare mutation
      consisting of a double-base pair substitution in the same codon (S252F). A
      phenotypical survey of our cases was performed and showed the clinical
      variability of this syndrome. In two patients there was no clinical or
      radiological evidence of craniosynostosis. In two other patients with atypical
      forms of syndactyly and cranial abnormalities, the detection of a specific
      mutation was helpful in making the diagnosis. CONCLUSIONS: The P253R mutation
      appears to be associated with the more severe forms, with regard to the forms of
      syndactyly and to mental outcome. The fact that mutations found in patients with
      Apert' s syndrome are usually confined to a specific region of the FGFR2 exon
      IIIa may be useful in making the diagnosis and allowing genetic counseling in
      difficult cases.

PMID- 10067912
TI  - Failure of third ventriculostomy in the treatment of aqueductal stenosis in
      children.
AB  - OBJECT: The goal of this study was to analyze the types of failure and long-term
      efficacy of third ventriculostomy in children. METHODS: The authors
      retrospectively analyzed clinical data obtained in 213 children affected by
      obstructive triventricular hydrocephalus who were treated by third
      ventriculostomy between 1973 and 1997. There were 120 boys and 93 girls. The
      causes of the hydrocephalus included: aqueductal stenosis in 126 cases;
      toxoplasmosis in 23 cases, pineal, mesencephalic, or tectal tumor in 42 cases;
      and other causes in 22 cases. In 94 cases, the procedure was performed using
      ventriculographic guidance (Group I) and in 119 cases by using endoscopic
      guidance (Group II). In 19 cases (12 in Group I and seven in Group II) failure
      was related to the surgical technique. Three deaths related to the technique were
      observed in Group I. For the remaining patients, Kaplan-Meier survival analysis
      showed a functioning third ventriculostomy rate of 72% at 6 years with a mean
      follow-up period of 45.5 months (range 4 days-17 years). No significant
      differences were found during long-term follow up between the two groups. In
      Group I, a significantly higher failure rate was seen in children younger than 6
      months of age, but this difference was not observed in Group II. Thirty-eight
      patients required reoperation (21 in Group I and 17 in Group II) because of
      persistent or recurrent intracranial hypertension. In 29 patients shunt placement
      was necessary. In nine patients in whom there was radiologically confirmed
      obstruction of the stoma, the third ventriculostomy was repeated; this was
      successful in seven cases. Cine phase-contrast (PC) magnetic resonance (MR)
      imaging studies were performed in 15 patients in Group I at least 10 years after
      they had undergone third ventriculostomy (range 10-17 years, median 14.3 years);
      this confirmed long-term patency of the stoma in all cases. CONCLUSIONS: Third
      ventriculostomy effectively controls obstructive triventricular hydrocephalus in
      more than 70% of children and should be preferred to placement of extracranial
      cerebrospinal shunts in this group of patients. When performed using
      ventriculographic guidance, the technique has a higher mortality rate and a
      higher failure rate in children younger than 6 months of age and is, therefore,
      no longer preferred. When third ventriculostomy is performed using endoscopic
      guidance, the same long-term results are achieved in children younger than 6
      months of age as in older children and, thus, patient age should no longer be
      considered as a contraindication to using the technique. Delayed failures are
      usually secondary to obstruction of the stoma and often can be managed by
      repeating the procedure. Midline sagittal T2-weighted MR imaging sequences
      combined with cine PC MR imaging flow measurements provide a reliable tool for
      diagnosis of aqueductal stenosis and for ascertaining the patency of the stoma
      during follow-up evaluation.

PMID- 10067913
TI  - Preoperative identification of meningiomas that are highly likely to recur.
AB  - OBJECT: Although generally they are well-circumscribed benign tumors, meningiomas
      recur even after complete removal. The aims of this study are to identify
      preoperatively groups of patients who have a high risk of meningioma recurrence
      by reviewing their clinicoradiological features and to plan appropriate
      treatments. METHODS: One hundred one patients who underwent macroscopically
      complete removal of meningiomas were observed postoperatively for at least 5
      years or until tumor recurrence. Preoperative radiological findings and clinical
      characteristics were assessed. Fifteen meningiomas recurred during the follow-up
      period, which extended to a maximum duration of 18 years. On univariate analysis,
      tumor size and shape, relation to the major sinuses, calcification, bone changes,
      and characteristics of the tumor-brain interface were significant predictive
      factors for recurrence. Patient age and gender were not deemed significant.
      Multivariate analysis revealed that only the shape of the tumor was significant;
      both "mushrooming" and lobulated meningiomas were more likely to recur than round
      ones. Recurrences most frequently occurred at the edge of the dural resection
      after a Simpson Grade I removal, whereas local recurrences were predominant after
      a Simpson Grade II or III removal. CONCLUSIONS: Meningiomas with mushrooming or
      lobulated shapes should be treated more aggressively with a wider dural excision.
      This is not usually necessary for round tumors, although it may be beneficial in
      younger patients.

PMID- 10067914
TI  - Changes in hemodynamics of the carotid and middle cerebral arteries before and
      after endoscopic sympathectomy in patients with palmar hyperhidrosis: preliminary
      results.
AB  - OBJECT: The purpose of this study was to analyze the change in carotid and middle
      cerebral artery (MCA) hemodynamics before and after endoscopic upper thoracic
      sympathectomy in patients with palmar hyperhidrosis (PH). METHODS: Sixty-eight
      patients with PH (35 males and 33 females) for whom the average age was 24.5+/
      10.7 years (+/- standard deviation) were recruited into this study. These
      patients all underwent routine upper T-2 sympathectomy to treat their PH.
      Ultrasonography studies of the carotid arteries (CAs) and MCA were obtained in
      each patient before and after T-2 sympathectomy. The blood flow volume, flow
      velocity, and resistivity index (RI) in the bilateral common CAs (CCAs), internal
      CAs (ICAs), and external CAs (ECAs) were evaluated using duplex ultrasonography.
      The systolic peak velocity, mean velocity, diastolic peak velocity, pulsatility
      index, and RI of the bilateral MCAs were evaluated using transcranial Doppler
      ultrasonography. Blood pressure and heart rate were also recorded during this
      study. The Student paired t-test was used to analyze the differences between
      studies before and after bilateral T-2 sympathectomy. There was a significant
      reduction in diastolic pressure after T-2 sympathectomy (p = 0.003), but not in
      systolic pressure or heart rate. The vessel diameter was increased after
      sympathectomy in the left CAs and right CCA. The T-2 sympathectomy led to
      significant elevation of blood flow volume and RI in the left CCA, ICA, and ECA
      (p < 0.05). The authors found significant increases in maximum flow velocity and
      RI in the left MCA (p < 0.05). CONCLUSIONS: Patients who underwent T-2
      sympathectomy demonstrated a significant increase in blood flow volume and flow
      velocities of the CAs and MCA, especially on the left side. Asymmetry of
      sympathetic influence on the hemodynamics of the CAs and MCA was noted. The
      usefulness of sympathectomy for the treatment of ischemic cardiovascular and
      cerebrovascular disease deserves further investigation.

PMID- 10067915
TI  - Variability in lesion location after microelectrode-guided pallidotomy for
      Parkinson's disease: anatomical, physiological, and technical factors that
      determine lesion distribution.
AB  - OBJECT: To understand the factors that determine the distribution of lesions
      after microelectrode-guided pallidotomy for Parkinson's disease, the authors
      quantitatively characterized lesion location in a cohort of patients who were
      prospectively followed to determine the effects of pallidotomy on clinical
      outcome. METHODS: Thirty-three patients underwent volumetric magnetic resonance
      (MR) imaging after surgery to allow quantitative lesion localization in relation
      to conventional intraventricular landmarks and, alternatively, more anatomically
      relevant landmarks. The validity of the method was verified in a cohort of
      postpallidotomy patients who underwent concurrent volumetric and stereotactic MR
      imaging in an external head frame. Lesions were distributed over a considerable
      distance in the anteroposterior (8.8 mm) and mediolateral (8.7 mm) dimensions in
      relation to the anterior commissure and wall of the third ventricle,
      respectively. Less variation was seen in lesion location in the dorsoventral
      dimension (4.8 mm) in relation to the intercommissural plane. CONCLUSIONS: Lesion
      distribution was not random: lesion locations in the anteroposterior and
      mediolateral dimensions were highly correlated, such that lesions were
      distributed from anteromedial to posterolateral, parallel to the border of the
      globus pallidus internus with the obliquely oriented internal capsule. The
      factors that led to variability in lesion location were variation in third
      ventricle width and the oblique anteromedial-to-posterolateral course of the
      internal capsule. This demonstration of variability of lesion location in a
      cohort of patients who experienced excellent clinical benefits and minimal
      postoperative complications emphasizes the importance of anatomical variations in
      determining lesion position and the need for physiological corroboration for
      correct lesion placement.

PMID- 10067916
TI  - Localization of somatosensory function by using positron emission tomography
      scanning: a comparison with intraoperative cortical stimulation.
AB  - OBJECT: To investigate the utility of [15O]H2O positron emission tomography (PET)
      activation studies in the presurgical mapping of primary somatosensory cortex,
      the authors compared the magnitude and location of activation foci obtained using
      PET scanning with the results of intraoperative cortical stimulation (ICS).
      METHODS: The authors used PET scanning and vibrotactile stimulation (of the face,
      hand, or foot) to localize the primary somatosensory cortex before surgical
      resection of mass lesions or epileptogenic foci affecting the central area in 20
      patients. With the aid of image-guided surgical systems, the locations of
      significant activation foci on PET scanning were compared with those of positive
      ICS performed at craniotomy after the patient had received a local anesthetic
      agent. In addition, the relationship between the magnitude and statistical
      significance of blood flow changes and the presence of positive ICS was examined.
      In 22 (95.6%) of 23 statistically significant (p < 0.05) PET activation foci,
      spatially concordant sites on ICS were also observed. Intraoperative cortical
      stimulation was positive in 40% of the PET activation studies that did not result
      in statistically significant activation. In the patients showing these results,
      there was a clearly identifiable t-statistic peak that was spatially concordant
      with the site of positive ICS in the sensorimotor area. All PET activation foci
      with a t statistic greater than 4.75 were associated with spatially concordant
      sites of positive ICS. All PET activation foci with a t statistic less than 3.2
      were associated with negative ICS. CONCLUSIONS: Positron emission tomography is
      an accurate method for mapping the primary somatosensory cortex before surgery.
      The need for ICS, which requires local anesthesia, may be eliminated when PET
      foci with high (> 4.75) or low (< 3.20) t-statistic peaks are elicited by
      vibrotactile stimulation.

PMID- 10067917
TI  - The parasellar region of human infants: cavernous sinus topography and surgical
      approaches.
AB  - OBJECT: In this study the authors analyze the peculiarities of the parasellar
      anatomy and the topography of surgical approaches to the parasellar region (PSR)
      in human infants. METHODS: Forty-nine specimens of the PSR obtained at autopsy
      were studied using microdissection and histological analysis. Important distances
      between anatomical landmarks were measured with the aid of a dissecting
      microscope. One serially sectioned specimen was three-dimensionally reconstructed
      and analyzed on the computer screen by using the authors' new episcopic
      reconstruction technique. CONCLUSIONS: The anatomy of the infant PSR differs
      distinctly from that of the adult. The parasellar portion of the internal carotid
      artery (ICA) does not form a siphon, but takes a straight course, and the venous
      pathways as well as the cranial and sympathetic nerves have different
      topographical relationships. Analyses of surgical approaches demonstrate that, in
      young children, the anterolateral approach can be used to reach the
      pterygopalatine compartment, the superior ophthalmic vein, and those pathological
      processes that extend from the orbit into the PSR. The approach via Parkinson's
      triangle can be used in 45% of cases to access the pathological processes that
      occur in the voluminous space above and behind the posterior flexure of the
      parasellar ICA. Taking this route, sympathetic nerve fibers passing through the
      PSR are not at risk, but some arterial branches that run within the lateral wall
      of the sinus can complicate this approach. This study presents a guideline that
      can assist radiologists and neurosurgeons in the planning and performance of
      interventions within the PSR of neonates and young children.

PMID- 10067918
TI  - Ultra-early clot aspiration after lysis with tissue plasminogen activator in a
      porcine model of intracerebral hemorrhage: edema reduction and blood-brain
      barrier protection.
AB  - OBJECT: Ultra-early hematoma evacuation (< 4 hours) after intracerebral
      hemorrhage (ICH) may reduce mass effect and edema development and improve
      outcome. To test this hypothesis, the authors induced lobar hematomas in pigs.
      METHODS: The authors infused 2.5 ml of blood into the frontal cerebral white
      matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with
      tissue plasminogen activator ([tPA], 0.3 mg) and aspirated at 3.5 hours after
      hematoma induction. Brains were frozen in situ at 24 hours post-ICH and hematomal
      and perihematomal edema volumes were determined on coronal sections by using
      computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated
      cerebral tissue pressure from 12.2+/-1.3 to 2.8+/-0.8 mm Hg. At 24 hours, prior
      clot removal markedly reduced hematoma volumes (0.40+/-0.10 compared with 1.26+/
      0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28+/-0.05 compared with
      1.46+/-0.24 cm3, p < 0.005), compared with unevacuated control lesions.
      Furthermore, no Evans blue dye staining of perihematomal edematous white matter
      was present in brains in which the hematomas had been evacuated, compared with
      untreated controls. CONCLUSIONS: Hematomas were quickly and easily aspirated
      after treatment with tPA, resulting in significant reductions in mass effect.
      Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of
      the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the
      development of vasogenic edema. These findings in a large-animal model of ICH
      provide support for clinical trials that include the use of fibrinolytic agents
      and ultra-early stereotactically guided clot aspiration for treating ICH.

PMID- 10067919
TI  - Correlations between the apparent diffusion coefficient, water content, and
      ultrastructure after induction of vasogenic brain edema in cats.
AB  - OBJECT: The authors examined the correlation between changes in the apparent
      diffusion coefficient, regional water content, and tissue ultrastructure after
      vasogenic brain edema. METHODS: Vasogenic edema was induced in the white matter
      of six cats by cortical cold lesioning. The trace of diffusion tensor (Trace[D])
      obtained from magnetic resonance imaging to measure the orientationally averaged
      water diffusibility was compared with the corresponding tissue water content
      determined by gravimetric studies and with ultrastructural water localization.
      Edema fluid had spread to the subcortical and deep white matter by 4.5 hours
      postlesioning. The increase in Trace(D) showed a significant linear correlation
      with the increase in tissue water content, both in the subcortical and deep white
      matter as follows: y = 45.5x - 2367 (r = 0.94) and y = 37.0x - 1769 (r = 0.93),
      respectively, where x is the water content (gram water/gram tissue) and y the
      Trace(D) (x 10(-6) mm2/second). On histological examination, nerve fibers were
      found to be dissociated in the white matter and the extracellular space was
      markedly enlarged with protein-rich fluid. No noticeable hydropic swelling of the
      cellular components was observed. CONCLUSIONS: A linear correlation was observed
      between increases in Trace(D) and increases in extracellular water volume in in
      vivo vasogenic brain edema. A similar correlation between the subcortical and
      deep white matter showing different arrangements of nerve fibers (parallel
      compared with intermingled, respectively) indicated that measurement of Trace(D)
      is a suitable parameter for the evaluation of vasogenic brain edema.

PMID- 10067920
TI  - Improved motor outcome in response to magnesium therapy received up to 24 hours
      after traumatic diffuse axonal brain injury in rats.
AB  - OBJECT: The goal of this study was to establish the therapeutic window during
      which delayed therapy with MgSO4 improves neurological motor outcome in rats that
      have suffered severe traumatic axonal brain injury. METHODS: Severe brain injury
      was induced in male Sprague-Dawley rats by using the impact-acceleration model of
      severe traumatic diffuse axonal brain injury. Injured animals were subsequently
      treated with MgSO4 (750 micromol/kg) infused intramuscularly at 30 minutes or at
      8, 12, or 24 hours after trauma and were tested for neurological motor outcome
      during the following week by using the rotarod test. Injured untreated (control)
      animals demonstrated highly significant (p < 0.001) neurological motor deficits
      that were sustained over the 1-week assessment period. Animals treated with MgSO4
      at 30 minutes or at 8 or 12 hours postinjury demonstrated significantly improved
      motor outcomes compared with untreated control animals at all time points (0.001
      < p < 0.05). Animals treated with MgSO4 at 24 hours had motor scores that were
      similar to those of untreated control animals early in the week, but demonstrated
      a significantly more rapid recovery in function and, by the end of the assessment
      period, they demonstrated significantly improved motor scores (p < 0.01).
      Repeated administration of MgSO4 over the 1-week observation period did not
      further improve outcome. CONCLUSIONS: The present results demonstrate that Mg++
      plays a neuroprotective role following severe diffuse traumatic axonal brain
      injury. Moreover, Mg++ therapy significantly improved motor outcome when
      administered up to 24 hours after injury, with early treatments providing the
      most significant benefit. Repeated administration beyond 24 hours postinjury did
      not provide additional neuroprotection.

PMID- 10067921
TI  - Influence of early posttraumatic hypothermia therapy on local cerebral blood flow
      and glucose metabolism after fluid-percussion brain injury.
AB  - OBJECT: Using autoradiographic image averaging, the authors recently described
      prominent foci of marked glucose metabolism-greater-than-blood-flow uncoupling in
      the acutely traumatized rat brain. Because hypothermia is known to ameliorate
      injury in this and other injury models, the authors designed the present study to
      assess the effects of posttraumatic therapeutic hypothermia on the local cerebral
      metabolic rate of glucose (LCMRglu) and local cerebral blood flow (LCBF)
      following moderate parasagittal fluid-percussion head injury (FPI) in rats.
      METHODS: Either cranial hypothermia (30 degrees C) or normothermia (37 degrees C)
      was induced for 3 hours in matched groups of rats immediately after FPI; LCMRglu
      and LCBF were assessed 3 hours after concluding these temperature manipulations.
      In rats subjected to FPI, regardless of whether normothermia or hypothermia
      ensued, LCBF was reduced relative to the sham-injury groups. In addition, when
      FPI was followed by hypothermia (FPI-30 degrees C group), the subsequent LCBF was
      significantly lower (35-38% on average) than in FPI-37 degrees C rats.
      Statistical mapping of LCBF difference imaging data revealed confluent cortical
      and subcortical zones of significantly reduced LCBF (largely ipsilateral to the
      prior injury) in FPI-30 degrees C rats relative to the FPI-37 degrees C group.
      Local glucose utilization was reduced in both hemispheres of FPI-37 degrees C
      rats relative to the sham-injury group and was lower in the right (traumatized)
      hemisphere than in the left. However, LCMRglu values were largely unaffected by
      temperature manipulation in either the FPI or sham-injury groups. The
      LCMRglu/LCBF ratio was nearly doubled in FPI-30 degrees C rats relative to the
      FPI-37 degrees C group, in a diffuse and bihemispheric fashion. Linear regression
      analysis comparing LCMRglu and LCBF revealed that the FPI-37 degrees C and FPI-30
      degrees C data sets were completely nonoverlapping, whereas the two sham-injury
      data sets were intermixed. CONCLUSIONS: Despite its proven neuroprotective
      efficacy, early posttraumatic hypothermia (30 degrees C for 3 hours) nonetheless
      induces a moderate decline in cerebral perfusion without the (anticipated)
      improvement in cerebral glucose utilization, so that a state of mild metabolism
      greater-than-blood-flow dissociation is perpetuated.

PMID- 10067922
TI  - Effect of cerebral perfusion pressure on contusion volume following impact
      injury.
AB  - OBJECT: Although it is generally acknowledged that a sufficient cerebral
      perfusion pressure (CPP) is necessary for treatment of severe head injury, the
      optimum CPP is still a subject of debate. The purpose of this study was to
      investigate the effect of various levels of blood pressure and, thereby, CPP on
      posttraumatic contusion volume. METHODS: The left hemispheres of 60 rats were
      subjected to controlled cortical impact injury (CCII). In one group of animals
      the mean arterial blood pressure (MABP) was lowered for 30 minutes to 80, 70, 60,
      50, or 40 mm Hg 4 hours after contusion by using hypobaric hypotension. In
      another group of animals the MABP was elevated for 3 hours to 120 or 140 mm Hg 4
      hours after contusion by administering dopamine. The MABP was not changed in
      respective control groups. Intracranial pressure (ICP) was monitored with an ICP
      microsensor. The rats were killed 28 hours after trauma occurred and contusion
      volume was assessed using hematoxylin and eosin-stained coronal slices. No
      significant change in contusion volume was caused by a decrease in MABP from 94
      to 80 mm Hg (ICP 12+/-1 mm Hg), but a reduction of MABP to 70 mm Hg (ICP 9+/-1 mm
      Hg) significantly increased the contusion volume (p < 0.05). A further reduction
      of MABP led to an even more enlarged contusion volume. Although an elevation of
      MABP to 120 mm Hg (ICP 16+/-2 mm Hg) did not significantly affect contusion
      volume, there was a significant increase in the contusion volume at 140 mm Hg
      MABP (p < 0.05; ICP 18+/-1 mm Hg). CONCLUSION: Under these experimental
      conditions, CPP should be kept within 70 to 105 mm Hg to minimize posttraumatic
      contusion volume. A CPP of 60 mm Hg and lower as well as a CPP of 120 mm Hg and
      higher should be considered detrimental.

PMID- 10067923
TI  - Glutathione monoethyl ester and inhibition of the oxyhemoglobin-induced increase
      in cytosolic calcium in cultured smooth-muscle cells.
AB  - OBJECT: The mechanism of arterial vasoconstriction caused by oxyhemoglobin
      production after subarachnoid hemorrhage was investigated. METHODS: Using a
      fluorescent Ca++ indicator (fura-2 acetoxymethyl ester), the change in the
      cytosolic intracellular Ca++ concentration, [Ca++]i. was measured in cultured rat
      vascular smooth-muscle cells exposed to oxyhemoglobin and other substances.
      Oxyhemoglobin induced transient elevation of smooth-muscle cell [Ca++]i in either
      the presence or absence of ethyleneglycol-bis (beta-aminoethylether)-N,N'
      tetraacetic acid, indicating that Ca++ released by oxyhemoglobin was derived from
      [Ca++]i stores. In contrast, methemoglobin had no effect on the smooth-muscle
      cells. Exposure of the cells to reactive oxygen species generated by xanthine
      plus xanthine oxidase yielded the same results as with oxyhemoglobin, that is,
      transient elevation of smooth-muscle cell [Ca++]i. Procaine (a Ca++ channel
      blocker) failed to inhibit the oxyhemoglobin-induced elevation of [Ca++]i.
      Ryanodine (a Ca++ channel opener) plus oxyhemoglobin caused markedly greater
      elevation of [Ca++]i than ryanodine alone, whereas thapsigargin (an adenosine
      triphosphate [ATP]-dependent Ca++ pump inhibitor) plus oxyhemoglobin had no
      additional effect when compared with thapsigargin alone. The oxyhemoglobin
      induced elevation of [Ca++]i could be blocked by an Fe++ chelator (ferene), but
      not by an Fe chelator (deferoxamine mesylate). Treatment with either
      dithiothreitol or glutathione monoethyl ester markedly inhibited the
      oxyhemoglobin-induced elevation of [Ca++]i. CONCLUSIONS: These results indicate
      that Fe++-catalyzed hydroxyl radicals generated from oxyhemoglobin-derived free
      radicals induce the elevation of [Ca++]i by inhibiting the ATP-dependent Ca++
      pump rather than the Ca++ channels in the sarcoplasmic reticulum and that thiols
      may prevent Ca++ pump inactivation by inhibiting the oxidation of membrane
      sulfhydryl groups.

PMID- 10067924
TI  - Tamoxifen radiosensitization in human glioblastoma cell lines.
AB  - OBJECT: A combined tamoxifen and radiation therapy is being used in clinical
      trials to treat glioblastoma multiforme (GBM). The rationale behind this therapy
      is that tamoxifen is a radiosensitizer. However, the evidence for this is weak.
      The authors, therefore, examined the effect of combined radiation-tamoxifen
      therapy in three GBM cell lines of human origin. METHODS: The GBM cell lines were
      exposed to different concentrations (0.3-5 microg/ml) of tamoxifen and
      subsequently irradiated at varying doses (0.8-5 Gy). Tumor growth inhibition was
      measured using a proliferation assay. The interaction of tamoxifen and radiation
      therapies was quantified using the combination index method, which distinguishes
      whether a combined antitumor effect is synergistic, additive, or antagonistic. At
      high doses of tamoxifen or radiation there was significant inhibition of tumor
      cell proliferation. At low doses of either therapeutic agent, there was little
      effect. In one cell line, synergism occurred at high doses of tamoxifen and
      radiation. In the other two cell lines, an additive effect was observed. In only
      one of the three cell lines was there synergy between tamoxifen and radiation at
      doses that significantly inhibited tumor proliferation. CONCLUSIONS: Because
      synergy could not be demonstrated in all three cell lines at active dosages, the
      clinical combination of tamoxifen and radiation therapies may not be of benefit
      to all patients.

PMID- 10067925
TI  - Anatomical and embryological considerations in the repair of a large vertex
      cephalocele. Case report.
AB  - The case of a neonate with a large vertex cephalocele is presented. The
      anatomical features of this anomaly were evaluated by means of magnetic resonance
      imaging and magnetic resonance angiography. Fusion of the thalami, dysgenesis of
      the corpus callosum, and failure of adequate formation of the interhemispheric
      fissure were characteristics of the major cerebral anomalies associated with the
      cephalocele. The absence of a falx in the midline, a split configuration of the
      superior sagittal sinus, and a dysgenetic tentorium with a concomitant abnormal
      venous drainage pattern were found in association with a large dorsal cyst.
      Repair of the anomaly was undertaken on the 3rd postnatal day. A cerebrospinal
      fluid shunt was required to treat hydrocephalus on Day 30. The child is well at
      age 3 years, but with significant developmental delay. The pathogenesis of this
      vertex cephalocele relates to semilobar holoprosencephaly and dorsal cyst
      formation. In addition, a disturbance in the separation of the diencephalic
      portion of the neural tube from the surface ectoderm or skin during the final
      phases of neurulation had occurred to help create the large cephalocele. Detailed
      preoperative imaging studies and awareness of the embryology and anatomy of this
      lesion facilitated the repair of the cephalocele. The prognosis of the child is
      determined not only by the presence of hydrocephalus, but also by the number of
      associated major cerebral anomalies. Options for treatment are discussed.

PMID- 10067926
TI  - Surgically created fourth-third cranial nerve communication: temporary success in
      a child with bilateral third nerve hamartomas. Case report.
AB  - Shortly after birth, an otherwise healthy infant developed eye deviation and
      ptosis due to a hamartomatous lesion of the interpeduncular segment of the right
      oculomotor nerve. The left nerve became similarly involved when the child was 1.5
      years of age. Direct nerve repair was not possible. Instead, the trochlear nerve
      was divided and its proximal end was attached to the distal end of the third
      nerve. Elevation of the upper eyelid and partial adduction of the eye developed
      gradually over the ensuing 3 to 5 months. Both functions were lost after an
      additional 2 months, presumably as a result of tumor recurrence or neuroma
      formation. This case report shows that surgically created fourth-third cranial
      nerve communication is feasible and may merit consideration under similar
      circumstances.

PMID- 10067927
TI  - Primary cerebellar glioblastomas multiforme in children. Report of four cases.
AB  - Primary cerebellar glioblastomas multiforme are exceedingly rare in children. The
      authors therefore retrospectively characterized the clinical behavior and
      pathological features of these tumors. A review of the database at the Hospital
      for Sick Children, Toronto, Canada revealed four patients with cerebellar tumors
      that displayed significant pleomorphism, hypercellularity, mitoses, and necrosis
      with pseudopalisading. The authors performed a detailed clinical, radiological,
      histological, and immunohistochemical analysis of the tumors in these four
      children (three boys and one girl; average age at presentation 7 years; range 21
      months-15 years). Magnetic resonance imaging and computerized tomography most
      commonly revealed a large lesion with minimal edema, inhomogeneous contrast
      enhancement, and a discrete border. Tumor resection was subtotal in one patient
      and gross total in three patients. Immunostaining of the tumor cells with
      antisera to glial fibrillary acidic protein and vimentin was positive in varying
      degrees. Initial adjuvant therapy consisted of local radiation only (one
      patient), chemotherapy only (one patient), and radiation and chemotherapy (one
      patient). One patient received no adjuvant therapy. Tumor recurrence was
      documented in all patients: two local recurrences (at 3.5 and 7 months), one
      spinal recurrence (at 14 months), and one local recurrence with ventricular and
      spinal spread (at 8 months). Ultimately, three of the four patients developed
      leptomeningeal tumor spread. Patient follow up ranged from 8 to 17 months (mean
      12.5 months). Three patients were dead at last follow up with a mean survival of
      15 months. The prognosis for patients with cerebellar glioblastomas is extremely
      poor, and the tumor has a tendency for cerebrospinal fluid dissemination. The
      optimal management of patients harboring of these difficult-to-treat tumors,
      including the role of craniospinal radiation and chemotherapy, has not yet been
      achieved.

PMID- 10067928
TI  - Stereotactic pallidotomy in a child with Hallervorden-Spatz disease. Case report.
AB  - The authors present a case of Hallervorden-Spatz disease (HSD) in a 10-year-old
      boy treated with stereotactic pallidotomy for control of severe dystonia.
      Hallervorden-Spatz disease is a rare type of neuraxonal dystrophy that can be
      familial or sporadic. This is the first case of HSD reported in the literature in
      which a pallidotomy was performed. The patient had progressively worsening
      dystonias and spasms that prevented useful function of his entire right side and
      eventually threatened his respiratory ability. Pre- and postoperative magnetic
      resonance images are presented along with electrophysiological recordings made in
      the globus pallidus at the time of surgery. Functional improvement in the use of
      the patient's limbs and relief from the painful dystonia were observed.
      Stereotactic pallidotomy should be considered as a potential treatment in the
      management of HSD.

PMID- 10067929
TI  - Middle ear adenocarcinoma with intracranial extension. Case report.
AB  - Middle ear adenocarcinoma is a very rare, locally invasive neoplasm assumed to
      arise from the middle ear mucosa. Although endolymphatic sac tumor (aggressive
      papillary middle ear tumor) and jugulotympanic paraganglioma may show brain
      invasion, intracranial extension of histologically confirmed middle ear
      adenocarcinoma has not been previously reported. The authors describe a 53-year
      old man who suffered from otalgia and tinnitus for more than 10 years and from
      neurological deficits for 1 year due to a large temporal bone tumor that invaded
      the temporal lobe. A combined neurosurgical and otolaryngological resection was
      performed. Pathological analysis revealed a low-grade adenocarcinoma of a mixed
      epithelial-neuroendocrine phenotype, which showed a close histological similarity
      to, and topographical relationship with, middle ear epithelium. The authors
      conclude that middle ear adenocarcinoma belongs to the spectrum of extracranial
      tumors that have possible local extension to the brain.

PMID- 10067930
TI  - Late complications of Silastic duraplasty: low-virulence infections. Case report.
AB  - The authors describe three patients with expanding hemorrhagic mass lesions who
      presented 13 to 18 years after undergoing Silastic duraplasty. In all patients,
      results of bacteriological cultures of the masses obtained intraoperatively were
      positive, revealing low-virulence bacteria. Two of the patients were treated with
      antibiotic drugs and made a good recovery. The third did not receive antibiotic
      medications initially and later developed an epidural empyema that necessitated
      reoperation, but subsequently made a complete recovery. Vascularized neomembranes
      are generally agreed to be causes of the expanding masses, but the possibility
      that patients could be harboring chronic infections must be considered. Thus, on
      removal of duraplasty materials a complete bacteriological culture should be
      obtained, and if it is positive the proper antibiotic therapy should be
      administered. Furthermore, the creation of a registry of patients who have
      received implants is advocated to facilitate tracking of implanted material in
      case of complications.

PMID- 10067931
TI  - Intracranial Castleman's disease of solitary form. Case report.
AB  - This 62-year-old woman presented with clumsiness in her right hand. Magnetic
      resonance imaging demonstrated a small lesion mimicking a meningioma, which had
      arisen from the tentorium and contained notable edema. Full recovery was achieved
      by total removal of the lesion, which was diagnosed as a lymphoid mass resembling
      giant lymph node hyperplasia on histological examination. The lack of notable
      findings on whole-body and laboratory studies was compatible with a rare case of
      intracranial Castleman's disease of solitary form. The authors document clinical,
      neuroradiological, and pathological features of this rare disease.

PMID- 10067932
TI  - Saphenous vein interposition graft for recurrent carotid stenosis after prior
      endarterectomy and stent placement. Case report.
AB  - Although the use of carotid artery stents is increasing, the management of
      recurrent stenosis after their placement is undefined. The authors report on a
      patient who underwent two left carotid endarterectomies followed by left carotid
      angioplasty and stent placement for recurrent stenosis. A third symptomatic
      recurrence was subsequently managed by placement of a saphenous vein
      interposition graft from the common carotid artery to the distal cervical
      internal carotid artery. The patient remained without hemispheric or retinal
      ischemia at his 5-month follow-up visit. Interposition grafting should be
      considered as a treatment option for carotid restenosis after initial
      endarterectomy and stent placement.

PMID- 10067933
TI  - Recurrent stenosis of common carotid-intracranial internal carotid interposition
      saphenous vein bypass graft caused by intimal hyperplasia and treated with
      endovascular stent placement. Case report and review of the literature.
AB  - Intimal hyperplasia is a well-known cause of delayed stenosis in vein bypass
      grafts in all types of vascular surgery. Options for treatment of stenosis in
      peripheral and coronary artery bypass grafts include revision surgery and the
      application of endovascular techniques such as balloon angioplasty and stent
      placement. The authors present a case of stenosis caused by intimal hyperplasia
      in a high-flow common carotid artery-intracranial internal carotid artery (IICA)
      saphenous vein interposition bypass graft that had been constructed to treat a
      traumatic pseudoaneurysm of the intracavernous ICA. The stenosis recurred after
      revision surgery and was successfully treated by endovascular stent placement in
      the vein graft. The literature on stent placement for vein graft stenoses is
      reviewed, and the authors add a report of its application to external carotid
      internal carotid bypass grafts. Further study is required to define the role of
      endovascular techniques in the management of stenotic cerebrovascular disease.

PMID- 10067934
TI  - Resolution of central pain after embolization of an arteriovenous malformation.
      Case report.
AB  - The authors describe a patient with right-sided central pain resulting from a
      left parietal arteriovenous malformation (AVM). The AVM was treated with staged
      embolization and stereotactic radiosurgery, and its obliteration was documented
      on follow-up angiographic studies. Surprisingly, the patient noted complete
      resolution of her pain syndrome after embolization, which is an extremely rare
      result. Central pain and its proposed mechanisms are discussed.

PMID- 10067935
TI  - Hyperactive rhizopathy of the vagus nerve and microvascular decompression. Case
      report.
AB  - A 37-year-old woman underwent microvascular decompression of the superior
      vestibular nerve for disabling positional vertigo. Immediately following the
      operation, she noted severe and spontaneous gagging and dysphagia. Multiple
      magnetic resonance images were obtained but failed to demonstrate a brainstem
      lesion and attempts at medical management failed. Two years later she underwent
      exploration of the posterior fossa. At the second operation, the vertebral artery
      as well as the posterior inferior cerebellar artery were noted to be compressing
      the vagus nerve. The vessels were mobilized and held away from the nerve with
      Teflon felt. The patient's symptoms resolved immediately after the second
      operation and she has remained symptom free. The authors hypothesize that at
      least one artery was shifted at the time of her first operation, or immediately
      thereafter, which resulted in vascular compression of the vagus nerve. To the
      authors' knowledge, this is the first reported case of a hyperactive gagging
      response treated with microvascular decompression. The case also illustrates the
      occurrence of a possibly iatrogenic neurovascular compression syndrome.

PMID- 10067936
TI  - Thalamic stimulation and functional magnetic resonance imaging: localization of
      cortical and subcortical activation with implanted electrodes. Technical note.
AB  - The utility of functional magnetic resonance (fMR) imaging in patients with
      implanted thalamic electrodes has not yet been determined. The aim of this study
      was to establish the safety of performing fMR imaging in patients with thalamic
      deep brain stimulators and to determine the value of fMR imaging in detecting
      cortical and subcortical activity during stimulation. Functional MR imaging was
      performed in three patients suffering from chronic pain and two patients with
      essential tremor. Two of the three patients with pain had undergone electrode
      implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the
      other had undergone electrode implantation in both the Vc and the periventricular
      gray (PVG) matter. Patients with tremor underwent electrode implantation in the
      ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during
      stimulation by using a pulse generator connected to a transcutaneous extension
      lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body,
      PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim
      stimulation caused tremor arrest. Functional images were acquired using a 1.5
      tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias
      resulted in activation of the primary somatosensory cortex (SI). Stimulation at
      subthreshold intensities failed to activate the SI. Additional stimulation
      coupled activation was observed in the thalamus, the secondary somatosensory
      cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did
      not evoke paresthesias or activate the SI, but resulted in medial thalamic and
      cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal
      ganglia, and SI activation. An evaluation of the safety of the procedure
      indicated that significant current could be induced within the electrode if a
      faulty connecting cable (defective insulation) came in contact with the patient.
      Simple precautions, such as inspection of wires for fraying and prevention of
      their contact with the patient, enabled the procedure to be conducted safely.
      Clinical safety was further corroborated by performing 86 MR studies in patients
      in whom electrodes had been implanted with no adverse clinical effects. This is
      the first report of the use of fMR imaging during stimulation with implanted
      thalamic electrodes. The authors' findings demonstrate that fMR imaging can
      safely detect the activation of cortical and subcortical neuronal pathways during
      stimulation and that stimulation does not interfere with imaging. This approach
      offers great potential for understanding the mechanisms of action of deep brain
      stimulation and those underlying pain and tremor generation.

PMID- 10067937
TI  - Integration of preoperative and intraoperative functional brain mapping in a
      frameless stereotactic environment for lesions near eloquent cortex. Technical
      note.
AB  - The authors present a method of incorporating preoperative noninvasive functional
      brain mapping data into the frameless stereotactic magnetic resonance (MR)
      imaging dataset used for image-guided resection of brain lesions located near
      eloquent cortex. They report the use of functional (f)MR imaging and magnetic
      source (MS) imaging for preoperative mapping of eloquent cortex in difficult
      cases of brain tumor resection such as those in which there are large expansive
      masses or in which reoperations are required and the anatomy is distorted from
      prior treatments. To correlate methods of preoperative and intraoperative mapping
      localization directly, the authors have developed techniques of importing
      preoperative MS and fMR imaging data into an image-guided frameless stereotactic
      computer workstation. The data appear as a seamless overlay on the same
      preoperative volumetric MR imaging dataset used for stereotactic guidance during
      the operation. Intraoperatively identified functional locations mapped by
      cortical stimulation are recorded as digitally registered points. This approach
      should prove useful in assessing the accuracy and reliability of various
      preoperative functional brain mapping techniques.

PMID- 10067938
TI  - Henry G. Schwartz, M.D. 1909-1998. An obituary.

PMID- 10067939
TI  - Ependymomas in children.

PMID- 10067941
TI  - Hypothermia and head injury.

PMID- 10067940
TI  - Arteriovenous malformations and endothelin-1.

PMID- 10067942
TI  - Plurihormonal pituitary tumor.

PMID- 10067943
TI  - Primary melanoma.

PMID- 10067944
TI  - Direct convective macromolecule delivery.

PMID- 10067945
TI  - Violence in the lives of adult borderline patients.
AB  - The purpose of this study was to assess the experiences of adult violence
      reported by a sample of criteria-defined borderline patients and axis II
      controls. The experiences of having had a physically abusive partner and/or
      having been raped reported by 362 personality-disordered inpatients were assessed
      blind to diagnostic status using a semistructured research interview. Forty-six
      percent of borderline patients reported having been a victim of violence since
      the age of 18. Borderline patients (N = 290) were significantly more likely than
      axis II controls (N = 72) to report having had a physically abusive partner,
      having been raped, having been raped multiple times, having been raped by a known
      perpetrator, and having been both physically assaulted by a partner and raped.
      Female borderline patients were significantly more likely than male borderline
      patients to have been physically and/or sexually assaulted as adults (50% vs.
      26%). However, a significantly higher percentage of borderline patients of both
      genders reported experiences of adult violence than controls of the same gender.
      Four risk factors were found to significantly predict whether borderline patients
      had an adult history of being a victim of violence: female gender, a substance
      use disorder that began before the age of 18, childhood sexual abuse, and
      emotional withdrawal by a caretaker. The results of this study suggest that both
      male and female borderline patients are at substantial risk for being physically
      and/or sexually victimized as adults.

PMID- 10067946
TI  - Examining an affect regulation model of substance abuse in schizophrenia. The
      role of traits and coping.
AB  - Comorbid substance use disorders occur frequently in schizophrenia with
      significant detrimental effects to clinical outcome. Unfortunately, attempts to
      identify factors associated with comorbid substance use disorders (beyond
      demographic characteristics such as gender) have not been successful. This study
      examined an affect regulation model of comorbid substance use in schizophrenia
      with a focus on personality traits and coping. It was hypothesized that
      maladaptive coping and the traits of negative affect (NA) and disinhibition
      (DIS), but not trait positive affect (PA), would be associated with greater
      substance use problems. Thirty-nine patients with schizophrenia or
      schizoaffective disorder completed measures of personality traits, coping, and
      negative consequences associated with substance use. Traits were differentially
      associated with coping in that NA and DIS, but not PA, were associated with
      maladaptive coping including the use of drugs and alcohol to cope with stress.
      Alternatively, PA, but not DIS or NA, was related to adaptive coping strategies.
      Individuals high in NA and endorsing the use of drugs and alcohol to cope
      reported the greatest number of negative consequences from substance use. This
      finding held after controlling for gender. These results are consistent with an
      affect regulation model of substance use and suggest the advantage of examining
      the role of affect, traits, and coping in understanding comorbid substance use in
      schizophrenia.

PMID- 10067947
TI  - Long-term changes in defense style among patients recovering from major
      depression.
AB  - The long-term stability of ego defenses was examined in a group of 68 patients
      with major depression being treated in a rural private psychiatric practice.
      Current symptomatology and dispositional characteristics, including defense style
      (40-item Defense Style Questionnaire), were assessed pretreatment and at
      approximately 6 months and 2 years after treatment commenced. Age- and gender
      matched comparison groups were also selected from two community-based studies
      that utilized similar instruments and time periods. The major depression group
      reported significantly lower usage of mature defenses initially, but with
      recovery they moved progressively toward the range of mature defenses displayed
      by the nonpatient comparison group. Neurotic defenses were relatively stable
      throughout the study, as were immature defenses during the first 6 months.
      Comparisons between patients who discontinued treatment (N = 24) and those who
      remained in treatment (N = 33) revealed similar rates of symptom reduction;
      however, the latter group reported continuing reductions in their use of immature
      defenses, to a level below that of the nonpatient comparison group.

PMID- 10067948
TI  - Comparison of outcome between homogeneous and heterogeneous treatment
      environments in combat-related posttraumatic stress disorder.
AB  - This study compared treatment outcome at discharge, and 4, 8, and 12 month follow
      up between an inpatient program consisting of a mixture of Vietnam combat
      veterans with posttraumatic stress disorder (PTSD) and general psychiatric
      patients (N = 42), and the same program at a later period, consisting of only
      Vietnam combat veterans with PTSD (N = 33). Veterans rated the homogeneous
      environment higher in satisfaction, support, order, clarity, and amount of
      discussion of combat, and lower in hostility, than the heterogeneous condition.
      However, veterans showed no improvement in condition at 12 month follow-up, with
      the exception of decreased violence, replicating earlier studies. No differences
      in outcome were found between homogeneous or heterogeneous treatment
      environments. This study underscores the enduring nature of chronic posttraumatic
      stress disorder in the veteran population.

PMID- 10067949
TI  - Evaluating the tolerability of the newer antidepressants.
AB  - Given their equal efficacy, the choice of a specific antidepressant is largely
      influenced by side effect (SE) profiles. A number of new agents have recently
      become available. However, data directly comparing the side effects of these
      agents are scarce. As suggested by AHCPR guidelines, we used the 1998 Physicians'
      Desk Reference (PDR) to construct a comparison table using treatment emergent,
      placebo-adjusted incidence rates for the major (gastrointestinal, central nervous
      system, and sexual) side effects caused by nine antidepressants (fluoxetine,
      paroxetine, sertraline, fluvoxamine, nefazodone, bupropion SR, mirtazapine,
      venlafaxine XR, and citalopram). The results were tabulated to show the relative
      propensity of each drug to cause a particular side effect. Bupropion SR had the
      most favorable overall side-effect profile, and fluvoxamine the least favorable.
      However, there are several limitations in using the PDR to compare the newer
      antidepressants. Clinical studies directly comparing SEs of newer antidepressants
      are needed. Sexual SEs substantially affected total SE liability. A simplified
      summary table, with its advantages and some limitations, is not simple to
      construct. Pitfalls in this process are discussed.

PMID- 10067950
TI  - The relative influences of symptoms, insight, and neurocognition on social
      adjustment in schizophrenia and schizoaffective disorder.
AB  - Impaired insight and neurocognitive deficits are commonly seen in schizophrenia.
      No study to date, however, has documented the relative influences of insight
      deficits, neurocognitive functioning, and psychotic symptoms on overall social
      adjustment in this population. This was done in a cohort of individuals
      recovering from acute exacerbations. Forty-six individuals with schizophrenia or
      schizoaffective disorder were recruited upon discharge from an inpatient unit.
      Symptom levels, neurocognitive functioning (information processing, memory, and
      executive functioning), and symptom awareness were documented, and social
      adjustment was assessed in three domains: treatment compliance, social behavior,
      and subjective quality of life. Cross-sectional data from initial assessments are
      reported. Sequential linear regression analyses identified differential
      associations between illness characteristics and outcome domains. Treatment
      compliance was most influenced by insight; social behavior deficits were
      associated with thought disorder and neurocognitive (working memory and visuo
      spatial) impairments; and quality of life was associated with mood disturbances.
      Outcome is multidimensional in schizophrenia, and there are differential patterns
      of associations between illness characteristics and domains of social adjustment.
      Studies such as this can guide clinicians in determining the most appropriate
      treatments for specific individuals and should also guide researchers in efforts
      to clarify the processes that underlie treatment response and recovery in
      schizophrenia.

PMID- 10067951
TI  - Visual distortions and dissociation.
AB  - Visual distortions may be a frightening experience. They are often incorrectly
      diagnosed and easily dismissed. The causes of visual distortions are poorly
      understood. The aim of this study was to investigate the link between visual
      distortions and dissociative experiences in a nonclinical population. A total of
      297 nonclinical volunteers completed the Dissociative Experience Scale and
      answered questions concerning visual distortions. Our study suggests that visual
      distortions are quite common and that there is a clear link between visual
      distortions and dissociative phenomena. Literature indicates that this may be
      caused by disturbances in brain lateralization. Bilateral language capacity may
      interfere with abilities usually associated with the nondominant hemisphere.
      Research efforts attempting to shed light on the above matter may benefit our
      knowledge for dissociative phenomena. An interdisciplinary approach is needed.

PMID- 10067952
TI  - EEG abnormalities in nonmedicated panic disorder.

PMID- 10067953
TI  - Repetitive transcranial magnetic stimulation in the treatment of medication
      resistant depression: preliminary data.

PMID- 10067954
TI  - Mood and motivation disturbance in elderly subjects with and without dementia: a
      replication study.

PMID- 10067955
TI  - Personality as a predictor of the variability of insight in schizophrenia.

PMID- 10067956
TI  - Electrical stimulation as a therapeutic option to improve eyelid function in
      chronic facial nerve disorders.
AB  - PURPOSE: To establish whether it is possible to improve orbicularis oculi muscle
      function in the eyelids of patients with a chronic seventh cranial nerve palsy by
      using transcutaneous electrical stimulation to the point at which electrical
      stimulation induces a functional blink. METHODS: Ten subjects (one woman, nine
      men) aged 36 to 76 with chronic, moderate to severe facial nerve palsy were
      recruited into the study. Voluntary and spontaneous eyelid movements were
      assessed, using an optical measuring system, before, during, and after a 3-month
      treatment period. Voluntary and spontaneous lid velocities were also measured and
      compared with eyelid kinematic data in normal subjects (12 women, 18 men; age
      range, 22-56 years). RESULTS: Therapeutic electrical stimulation applied over 3
      months produced improvement in eyelid movement (>2 mm) in 8 of 10 patients during
      voluntary eyelid closure. However, there was no significant improvement recorded
      in spontaneous blink amplitudes or peak downward-phase velocity of the upper
      eyelid. This regimen of stimulation failed to recover function well enough that a
      functional blink could be induced in the paretic eyelid by electrical
      stimulation. CONCLUSIONS: Electrical stimulation using transcutaneous electrical
      nerve stimulators units can improve voluntary eye closure, apparently because of
      a reduction in stiffness of eyelid mechanics, rather than an improvement of
      muscle function. Investigation of alternative stimulation regimens is warranted.

PMID- 10067957
TI  - Immunoglobulin VH gene expression among extranodal marginal zone B-cell lymphomas
      of the ocular adnexa.
AB  - PURPOSE: Most lymphomas of the ocular adnexa are primary extranodal non-Hodgkin's
      lymphomas of the B-cell type, with the most common lymphoma subtype being the
      extranodal marginal-zone B-cell lymphoma (EMZL). Analysis of somatic mutations in
      the variable (V) region of the Ig heavy (H)-chain gene segment suggests that EMZL
      development in other locations is dependent on antigen stimulation. The purpose
      of this study was to analyze the presence of somatic hypermutations in clonally
      rearranged Ig H-chain V genes of this lymphoma entity in the ocular adnexa and to
      estimate whether the mutation pattern is compatible with antigen selection.
      METHODS: Twenty-six cases of EMZL of the ocular adnexa were diagnosed on the
      basis of morphology, histology, and immunohistology. A nested polymerase chain
      reaction (PCR) was performed on DNA extracted from paraffin sections. The
      isolated PCR products were sequenced and compared with published VH germline
      segments to determine the number of somatic mutations in the complementarity
      determining region (CDR) 2 and framework (FW) region 3. RESULTS: The number of
      somatic mutations in the cases of EMZL varied between 0 and 24: Five cases
      involved 0 to 3 somatic mutations, and the remaining 21 cases involved 4 to 24
      mutations. Based on the ratio of replacement (R) to silent (S) mutations in the
      CDR2 or FW3 regions, antigen selection seems to have occurred in 60% of ocular
      adnexal EMZL. The VH3 family was the most commonly expressed germline VH family
      (54%), followed by VH4 (23%), with biased usage of the latter. Some germline VH1
      genes used included DP-8, DP-10, DP-53, DP-63 (VH4.21), and DP-49, which are
      frequently used by autoantibodies (e.g., rheumatoid factors) and natural
      autoantibodies. CONCLUSIONS: EMZLs of the ocular adnexa have an Ig H-chain
      mutation pattern that supports the concept that they represent a clonal expansion
      of post-germinal-center memory B-cells in most instances. In two thirds of cases,
      antigen selection may have occurred, and autoantibodies may have a role in their
      development.

PMID- 10067958
TI  - Hyaluronan synthase expression in bovine eyes.
AB  - PURPOSE: Hyaluronan (HA), a high-molecular-weight linear glycosaminoglycan, is a
      component of the extracellular matrix (ECM). It is expressed in eyes and plays
      important roles in many biologic processes, including cell migration,
      proliferation, and differentiation. Hyaluronan is produced by HA synthase (HAS),
      which has three isoforms: HAS1, HAS2, and HAS3. In this study, the HAS expression
      in the anterior segment of bovine eyes was investigated to determine the
      significance of HA in eyes. METHODS: To obtain bovine HAS probes, degenerate
      oligonucleotide primers, based on well-conserved amino acid sequences including
      the catalytic region of each HAS isoform, were used for reverse transcription
      polymerase chain reaction to amplify mRNA from bovine corneal endothelial cells
      (BCECs). Hyaluronan synthase-1 expression in the anterior segment of bovine eyes
      at the protein level was investigated by immunohistochemistry. RESULTS: All three
      HAS isoforms were expressed in BCECs at the mRNA level. Amplified cDNA fragments
      of HAS1, HAS2, and HAS3 from BCECs can be aligned to human counterparts, showing
      similarities of 100%, 97.3%, and 100%, respectively, at the amino acid level.
      Hyaluronan synthase 1 was expressed at the protein level in corneal epithelium,
      keratocyte, corneal endothelium, conjunctival epithelium, ciliary epithelium,
      capillary endothelium, and trabecular meshwork. CONCLUSIONS: Hyaluronan synthase
      isoforms were expressed in the ocular anterior segment and are speculated to be
      involved in HA production in situ.

PMID- 10067959
TI  - Expression patterns of neurturin and its receptor components in developing and
      degenerative mouse retina.
AB  - PURPOSE: Neurturin (NTN) and its receptor components (GFRalpha2 and Ret) play an
      important role in the survival of different populations of neurons in the central
      and peripheral nervous systems. To gain insight into their possible functions
      throughout normal retinal development and during retinal neuronal apoptosis, the
      retinal distribution of expression of NTN and GFRalpha2 mRNAs and Ret protein
      were compared in control and retinal degeneration (rd) mice. METHODS: Eyes from
      control and rd animals were fixed in paraformaldehyde before sectioning. For in
      situ hybridization, retinal sections were hybridized with 35S-radiolabeled sense
      and antisense riboprobes for murine NTN and GFRalpha2 and were autoradiographed.
      Ret localization was detected by immunofluorescence. RESULTS: Neurturin mRNA
      expression was modulated through normal postnatal retinal development and was
      localized primarily to the inner retina and photoreceptor outer segments.
      GFRalpha2 mRNA displayed a diffuse developmental pattern of expression, but in
      the mature normal retina, NTN and GFRalpha2 mRNAs were more closely colocalized.
      Ret protein was localized particularly at the outer segments of photoreceptors,
      inner retina, and ganglion cell layers, but there were no prominent differences
      among genotypes. Increased NTN mRNA expression was detected in the retinal
      pigment epithelium and neural retina in concert with photoreceptor degeneration
      in rd mouse. In contrast, the level of GFRalpha2 mRNA was lower in rd compared
      with that in normal retina. CONCLUSIONS: These results suggest that NTN and its
      receptor are involved in retinal postnatal development and maintenance and that
      alterations in their transcription patterns are associated with inherited retinal
      degeneration.

PMID- 10067960
TI  - Effect of leukocytes on corneal cellular proliferation and wound healing.
AB  - PURPOSE: To establish whether fucoidin, by blocking the adhesion of leukocytes on
      the limbal vascular endothelium, prevents extravasation of the cells from the
      blood stream into the limbal stroma and the wounded area after corneal injury.
      Successful leukocyte blocking enabled investigation of the influence of
      leukocytes on corneal cellular proliferation after corneal wounding. METHODS:
      Thirty-two New Zealand White rabbits were used. Photorefractive keratectomy (PRK)
      and a standardized alkali corneal wound were used as models in two sets of
      experiments. In half of the injured rabbits fucoidin was used to prevent
      leukocytes from leaving the local vessels. The efficiency of the blocking
      technique was evaluated by counting the number of leukocytes in the limbal and
      wounded corneal areas. Proliferating cell nuclear antigen (PCNA) was used as a
      marker for proliferative activity. RESULTS: The infiltration of leukocytes into
      the limbus and the cornea after PRK and alkali injuries can be blocked by
      fucoidin. The healing rate of corneal epithelium after alkali burn was retarded
      in the absence of leukocytes. PCNA expression was enhanced in the presence of
      leukocytes. Fucoidin per se had no influence on corneal cell proliferation and
      wound healing. CONCLUSIONS: Polymorphonuclear leukocytes (PMNs) can be prevented
      from entering the cornea in vivo by fucoidin after PRK and after alkali burn. The
      corneal epithelial healing rate is delayed in the absence of PMNs in vivo, and
      PCNA expression increases in the presence of leukocytes.

PMID- 10067961
TI  - Zernike representation of corneal topography height data after nonmechanical
      penetrating keratoplasty.
AB  - PURPOSE: To demonstrate a mathematical method for decomposition of discrete
      corneal topography height data into a set of Zernike polynomials and to
      demonstrate the clinical applicability of these computations in the
      postkeratoplasty cornea. METHODS: Fifty consecutive patients with either Fuchs'
      dystrophy (n = 20) or keratoconus (n = 30) were seen at 3 months, 6 months, and 1
      year (before suture removal) and again after suture removal following
      nonmechanical trephination with the excimer laser. Patients were assessed using
      regular keratometry, corneal topography (TMS-1, simulated keratometry [SimK]),
      subjective refraction, and best-corrected visual acuity (VA) at each interval. A
      set of Zernike coefficients with radial degree 8 was calculated to fit two model
      surfaces: a complete representation (TOTAL) and a representation with parabolic
      terms only to define an approximate spherocylindrical surface (PARABOLIC). The
      root mean square error (RMS) was calculated comparing the corneal raw height data
      with TOTAL (TOTALRMS) and PARABOLIC (PARABOLICRMS). The cylinder of subjective
      refraction was correlated with the keratometric readings, the SimK, and the
      respective Zernike parameter. Visual acuity was correlated with the tilt
      components of the Zernike expansion. RESULTS: The measured corneal surface could
      be approximated by the composed surface 1 with TOTALRMS < or = 1.93 microm and by
      surface 2 with PARABOLICRMS < or = 3.66 microm. Mean keratometric reading after
      suture removal was 2.8+/-0.6 D. At all follow-up examinations, the SimK yielded
      higher values, whereas the keratometric reading and the refractive cylinder
      yielded lower values than the respective Zernike parameter. The correlation of
      the Zernike representation and the refractive cylinder (P = 0.02 at 3 months, P =
      0.05 at 6 months and at 1 year, and P = 0.01 after suture removal) was much
      better than the correlation of the SimK and refractive cylinder (P = 0.3 at 3
      months, P = 0.4 at 6 months, P = 0.2 at 1 year, and P = 0.1 after suture
      removal). Visual acuity increased from 0.23+/-0.10 at the 3-month evaluation to
      0.54+/-0.19 after suture removal. After suture removal, there was a statistically
      significant inverse correlation between VA and tilt (P = 0.02 in patients with
      keratoconus and P = 0.05 in those with Fuchs' dystrophy). CONCLUSIONS: Zernike
      representation of corneal topography height data renders a reconstruction of
      clinically relevant corneal topography parameters with a marked reduction of
      redundance and a small error. Correlation of amount/axis of refractive cylinder
      with respective Zernike parameters is more accurate than with keratometry or
      respective SimK values of corneal topography analysis.

PMID- 10067962
TI  - Androgen influence on lacrimal gland apoptosis, necrosis, and lymphocytic
      infiltration.
AB  - PURPOSE: Previous studies have shown that ovariectomy and hypophysectomy cause
      regression of the lacrimal gland and have implicated androgens as trophic
      hormones that support the gland. The purposes of this study were to test the
      hypothesis that glandular regression after ovariectomy is due to apoptosis, to
      identify the cell type or types that undergo apoptosis, to survey the time course
      of the apoptosis, and to determine whether ovariectomy-induced apoptosis could be
      prevented by dihydrotestosterone (DHT) treatment. METHODS: Groups of sexually
      mature female New Zealand White rabbits were ovariectomized and killed at various
      time periods up to 9 days. Additional groups of ovariectomized rabbits were
      treated with 4 mg/kg DHT per day. At each time period, sham-operated rabbits were
      used as controls. Lacrimal glands were removed and processed for analysis of
      apoptosis as assessed by DNA fragmentation and for morphologic examination. DNA
      fragmentation was determined using the TdT-dUTP terminal nick-end labeling assay
      and by agarose gel electrophoresis. Labeled nuclei were quantified by automated
      densitometry. Sections were also stained for RTLA (rabbit thymic lymphocyte
      antigen), rabbit CD18, and La antigen. Morphology was evaluated by both light and
      electron microscopy. RESULTS: The time course of apoptosis exhibited two phases,
      a rapid and transient phase and a second prolonged phase. A transient phase
      peaked at approximately 4 to 6 hours after ovariectomy. The values for degraded
      DNA as a percentage of total nuclear area were 4.29%+/-0.79% and 4.26%+/-0.54%,
      respectively. The values for sham-operated controls examined at the same time
      periods were 1.77%+/-0.08% and 0.82%+/-0.21%, respectively. The percentage of
      degraded DNA at 24 hours after ovariectomy was not different from controls
      examined at the same interval after sham operation. The percentage of degraded
      DNA 6 days after ovariectomy was significantly increased (8.5%+/-2.4%), compared
      with sham-operated animals at the same time period (0.68%+/-0.03%). DNA laddering
      was more pronounced after ovariectomy. Dihydrotestosterone treatment in
      ovariectomized rabbits suppressed the increase in DNA degradation. Morphologic
      examination of lacrimal gland sections indicated that ovariectomy caused
      apoptosis of interstitial cells rather than acinar or ductal epithelial cells.
      Tissue taken 4 hours and 6 days after ovariectomy showed nuclear chromatin
      condensation principally in plasma cells. Increased numbers of macrophages were
      also evident. Significant levels of cell degeneration and cell debris,
      characteristic of necrosis, were observed in acinar regions 6 days after
      ovariectomy. Dihydrotestosterone prevented this necrosis. Increased numbers of
      RTLA+, CD18+, and La+ interstitial cells were also evident 6 days after
      ovariectomy. In addition, ovariectomy increased La expression in ductal cells.
      Dihydrotestosterone treatment prevented the increase in numbers of lymphoid cells
      and La expression. Dihydrotestosterone also promoted the appearance of mitotic
      figures in acinar cells and increased the sizes of acini by 43% (P < 0.05).
      CONCLUSIONS: Glandular atrophy observed after ovariectomy is likely to proceed by
      necrosis of acinar cells rather than apoptosis. This process begins with an
      apparent time lag after a rapid phase of interstitial cell apoptosis. These
      processes are accompanied by increased lymphocytic infiltration. These results
      suggest that a critical level of androgen is necessary to maintain lacrimal gland
      structure and function and that a decrease in available androgen below this level
      could trigger lacrimal gland apoptosis and necrosis, and an autoimmune response.
      Because apoptotic and necrotic cell fragments may be sources of autoantigens that
      can be processed and presented to initiate an autoimmune reaction, we surmise
      that cell death triggered by androgen withdrawal may trigger an autoimmune
      response such as that encountered in Sjogren's syndrome. (ABSTRACT TRUNCATED)

PMID- 10067963
TI  - Estimation of corneal endothelial pump function in long-term contact lens
      wearers.
AB  - PURPOSE: To study the effects of long-term contact lens wear on morphologic and
      physiologic properties of corneal endothelial cells. METHODS: The endothelial
      permeability to fluorescein and the rate of corneal deswelling from hypoxia
      induced edema were measured in 20 long-term (mean, 17+/-9 years; range, 5-33
      years) contact lens wearers and 20 age-matched control subjects. From these data,
      the relative endothelial pump rate in each subject was estimated, based on the
      pump-leak hypothesis of corneal hydration control. Corneal autofluorescence and
      the aqueous humor flow rate were determined by fluorescein fluorophotometry.
      Images of corneal endothelial cells were recorded by using specular microscopy,
      and morphologic indices (cell density, coefficient of variation of cell area,
      percentage of hexagonal cells, and skewness) were determined. RESULTS: No
      statistically significant differences were found between the contact lens and
      control groups in endothelial permeability, corneal deswelling, relative
      endothelial pump rate ([mean +/- SD] 1.07+/-0.33 relative pump units versus
      1.01+/-0.25 relative pump units; contact lens versus control; P = 0.57), and
      endothelial cell density. Contact lens wearers had a significantly higher aqueous
      humor flow rate (3.57+/-1.03 microl/min versus 2.77+/-0.51 microl/min; P =
      0.005), coefficient of variation of cell area (0.35+/-0.09 versus 0.28+/-0.04; P
      = 0.006), and corneal autofluorescence (3.1+/-0.6 ng/ml versus 2.3+/-0.3 ng/ml
      fluorescein equivalents; P < 0.001) than did non-contact lens wearers.
      CONCLUSIONS: Despite the known effects of long-term contact lens wear on corneal
      endothelial morphometry, no effect on endothelial function was found.

PMID- 10067964
TI  - In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal
      angiogenesis.
AB  - PURPOSE: Numerous investigations have stressed the significance of leukocytes in
      early angiogenesis. Leukocytes invade the cornea, and the location of their
      extravasation corresponds to the site of vessel ingrowth. The interactions
      between leukocytes and vascular endothelium are mediated by various proteins,
      including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1).
      In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated
      in vivo. METHODS: Corneal neovascularization was induced in New Zealand White
      rabbits by use of intrastromal pellets containing 750 ng vascular endothelial
      growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain
      leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo
      by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a
      microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS:
      Limbal vessels showed increased leukocyte adhesion 24 hours after pellet
      implantation: The number of rolling and sticking leukocytes was significantly
      increased compared with the number in control animals (P < 0.01). Treatment with
      anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased
      leukocyte rolling. The area covered by new blood vessels was significantly
      diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results
      support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in
      early angiogenesis. This model may serve for investigation of the significance of
      adhesion molecules by in vivo observation and quantification.

PMID- 10067965
TI  - Effects of benzalkonium chloride on growth and survival of Chang conjunctival
      cells.
AB  - PURPOSE: The aim of this study was to investigate the action of benzalkonium
      chloride (BAC), used as a preservative in most ophthalmic topical solutions, on
      epithelial conjunctival cells in vitro. METHODS: A continuous human conjunctival
      cell line (Wong-Kilbourne derivative of Chang conjunctiva) was exposed to BAC
      solutions at various concentrations (0.1%-0.0001%) during a period of 10 minutes.
      Cells were examined before treatment and 3, 24, 48, and 72 hours later, after
      reexposure to normal cell culture conditions. Cell number and viability were
      assessed with crystal violet and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl
      tetrazolium bromide colorimetric assays. The expression of the apoptotic marker
      Apo 2.7, nuclear antigen p53, membrane proteins Fas and Fas ligand, and DNA
      content was studied by flow cytometry. Morphologic aspects of cell nuclei were
      analyzed on slides with a nucleic acid-specific dye, 4',6'-diamidino-2
      phenylindole dihydrochloride. Cytoskeleton was labeled with a monoclonal anti
      pancytokeratin antibody. In addition, apoptosis was measured by DNA
      electrophoresis assays in agarose gel. RESULTS: Cell exposure to 0.1% and 0.05%
      BAC induced cell lysis immediately after treatment. All cells (100%) treated with
      0.01% BAC died in a delayed manner within 24 hours, with most of the
      characteristics of apoptosis (chromatin condensation and DNA fragmentation,
      reduction in cell volume, expression of the apoptotic marker Apo 2.7, and
      apoptotic changes in DNA content). Aliquots of 0.005%, 0.001%, 0.0005%, and
      0.0001% BAC induced growth arrest and apoptotic cell death in a dose-dependent
      manner between 24 and 72 hours after treatment. The expressions of Fas and p53
      did not vary after BAC treatment. Fas ligand was always negative. CONCLUSIONS:
      These results suggest that BAC induces cell growth arrest and death at a
      concentration as low as 0.0001%. The mode of BAC-induced cell death is dose
      dependent. Cells die by necrosis after BAC treatment at high concentrations and
      by apoptosis if low concentrations of BAC are applied. This new aspect of in
      vitro toxicity of BAC could in part explain some ocular surface disorders
      observed in patients undergoing long-term topical treatments with preservative
      containing drugs.

PMID- 10067966
TI  - Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey.
AB  - PURPOSE: To determine the effect of latrunculin (LAT)-A, which binds to G-actin
      and disassembles actin filaments, on the pupil, accommodation, and isolated
      ciliary muscle (CM) contraction in monkeys. METHODS: Pupil diameter (vernier
      calipers) and refraction (coincidence refractometry) were measured every 15
      minutes from 0.75 to 3.5 hours after topical LAT-A 42 microg (approximately 10
      microM in the anterior chamber [AC]). Refraction was measured every 5 minutes
      from 0.5 to 1.5 hours after intracameral injection of 10 microl of 50 microM LAT
      A (approximately 5 microM in AC), with intramuscular infusion of 1.5 mg/kg
      pilocarpine HCl (PILO) during the first 15 minutes of measurements. Pupil
      diameter was measured at 1 and 2 hours, and refraction was measured every 5
      minutes from 1 to 2 hours, after intravitreal injection of 20 microl of 1.25 mM
      LAT-A (approximately 10 microM in vitreous), with intramuscular infusion of 1.5
      mg/kg PILO during the first 15 minutes of measurements (all after topical 2.5%
      phenylephrine), and contractile response of isolated CM strips, obtained <1 hour
      postmortem and mounted in a perfusion apparatus, to 10 microM PILO +/- LAT-A was
      measured at various concentrations. RESULTS: Topical LAT-A of 42 microg dilated
      the pupil without affecting refraction. Intracameral LAT-A of 5 microM inhibited
      miotic and accommodative responses to intramuscular PILO. Intravitreal LAT-A of
      10 microM had no effect on accommodative or miotic responses to intramuscular
      PILO. LAT-A dose-dependently relaxed the PILO-contracted CM by up to 50% at 3
      microM in both the longitudinal and circular vectors. CONCLUSIONS: In monkeys,
      LAT-A causes mydriasis and cycloplegia, perhaps related to its known ability to
      disrupt the actin microfilament network and consequently to affect cell
      contractility and adhesion. Effects of LAT-A on the iris and CM may have
      significant physiological and clinical implications.

PMID- 10067967
TI  - Directional and spectral reflectance of the rat retinal nerve fiber layer.
AB  - PURPOSE: To measure and describe the reflectance properties of a mammalian
      retinal nerve fiber layer (RNFL) and to determine the mechanisms responsible for
      the RNFL reflectance. METHODS: An isolated rat retina suspended across a slit in
      a black membrane and mounted in a black perfusion chamber provided high quality
      images of the RNFL. Imaging microreflectometry was used to measure RNFL
      reflectance at wavelengths from 400 nm to 830 nm and as a function of
      illumination angle. RESULTS: The directional reflectance of rat RNFL at all
      wavelengths was consistent with the theory of light scattering by cylinders; each
      nerve fiber bundle scattered light into a conical sheet coaxial with the bundle.
      There was no evidence of a noncylindrical component at any wavelength. Measured
      reflectance spectra were consistent between animals, similar to ones previously
      measured in macaque, and varied with scattering angle. All spectra could be
      described by a two-mechanism cylindrical scattering model with three free
      parameters. CONCLUSIONS: At all wavelengths the reflectance of rat RNFL arises
      from light scattering by cylindrical structures. The highly directional nature of
      this reflectance can be an important source of measurement variability in
      clinical assessment of the RNFL. The reflectance spectra reveal a combination of
      mechanisms: At wavelengths shorter than approximately 570 nm the reflectance
      comes from cylinders with diameters much smaller than the wavelength, but at
      wavelengths longer than approximately 680 nm the reflectance comes from cylinders
      with effective diameters of 350 nm to 900 nm.

PMID- 10067968
TI  - Test-retest variability of frequency-doubling perimetry and conventional
      perimetry in glaucoma patients and normal subjects.
AB  - PURPOSE: To compare the test-retest variability characteristics of frequency
      doubling perimetry, a new perimetric test, with those of conventional perimetry
      in glaucoma patients and normal control subjects. METHODS: The study sample
      contained 64 patients and 47 normal subjects aged 66.16+/-11.86 and 64.26+/-7.99
      years (mean +/- SD), respectively. All subjects underwent frequency-doubling
      perimetry (using the threshold mode) and conventional perimetry (using program 30
      2 of the Humphrey Field Analyzer; Humphrey Instruments, San Leandro, CA) in one
      randomly selected eye. Each test was repeated at 1-week intervals for five tests
      with each technique over 4 weeks. Empirical 5th and 95th percentiles of the
      distribution of threshold deviations at retest were determined for all
      combinations of single tests and mean of two tests, stratified by threshold
      deviation. The influence of visual field eccentricity and overall visual field
      loss on variability also were examined. RESULTS: Mean test time with frequency
      doubling perimetry in patients and normal control subjects was 5.90 and 5.25
      minutes, respectively, and with conventional perimetry was 17.20 and 14.01
      minutes, respectively. In patients, there was a significant correlation between
      the results of the two techniques, in the full field and in quadrants, whereas in
      normal subjects there was no such correlation. In patients, the retest
      variability of conventional perimetry in locations with 20-dB loss was 120%
      (single tests) and 127% (mean tests) higher compared with that in locations with
      0-dB loss. Comparative figures for frequency-doubling perimetry were 40% and 47%,
      respectively. Variability also increased more with threshold deviation in normal
      subjects tested with conventional perimetry. In both patients and normal
      subjects, variability increased with visual field eccentricity in conventional
      perimetry, but not in frequency-doubling perimetry. Both techniques showed an
      increase in variability with overall visual field damage. CONCLUSIONS: Frequency
      doubling perimetry has different test-retest variability characteristics than
      conventional perimetry and may have potential for monitoring glaucomatous field
      damage.

PMID- 10067969
TI  - Modifications to rat lens major intrinsic protein in selenite-induced cataract.
AB  - PURPOSE: To identify modifications to rat lens major intrinsic protein (MIP)
      isolated from selenite-induced cataract and to determine whether m-calpain (EC
      3.4.22.17) is responsible for cleavage of MIP during cataractogenesis. METHODS:
      Cataracts were induced in rats by a single injection of sodium selenite. Control
      and cataract lenses were harvested on day 16 and dissected into cortical and
      nuclear regions. Membranes were washed with urea buffer followed by NaOH. The
      protein was reduced/alkylated, delipidated, and cleaved with cyanogen bromide
      (CNBr). Cleavage products were fractionated by high-performance liquid
      chromatography (HPLC), and peptides were characterized by mass spectrometry and
      tandem mass spectrometry. MIP cleavage by m-calpain was carried out by incubation
      with purified enzyme, and peptides released from the membrane were analyzed by
      Edman sequencing. RESULTS: The intact C terminus, observed in the control nuclear
      and cataractous cortical membranes, was not observed in the cataractous nuclear
      membranes. Mass spectrometric analysis revealed heterogeneous cleavage of the C
      terminus of MIP in control and cataract nuclear regions. The major site of
      cleavage was between residues 238 and 239, corresponding to the major site of in
      vitro cleavage by m-calpain. However, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and mass spectrometric analysis indicated that in vivo
      proteolysis during cataract formation also included sites closer to the C
      terminus not produced by m-calpain in vitro. Evidence for heterogeneous N
      terminal cleavage was also observed at low levels with no differences between
      control and cataractous lenses. The major site of phosphorylation was determined
      to be at serine 235. CONCLUSIONS: Specific sites of MIP N- and C-terminal
      cleavage in selenite-induced cataractous lenses were identified. The
      heterogeneous cleavage pattern observed suggests that m-calpain is not the sole
      enzyme involved in MIP C-terminal processing in rat lens nuclei.

PMID- 10067970
TI  - Anterior polar cataracts in CS rats: a predictor of mature cataract formation.
AB  - PURPOSE: The objective of this study was to characterize the morphology of the
      anterior opacities formed during recovery from posterior subcapsular cataract
      (PSC) in Royal College of Surgeons (RCS) rats. METHODS: Lenses from RCS rats at 8
      and 12 weeks postnatal (n = 14 and 12, respectively) were examined under a
      dissecting microscope for the presence of anterior opacities. Lenses with
      anterior opacities were fixed, embedded in epoxy resin, and sectioned along the
      optic axis for light microscopy (LM) and transmission electron microscopy (TEM).
      RESULTS: At eight weeks postnatal, 21.5% of animals (3/14) had anterior
      cataracts. Light microscopy of 1- to 2-microm-thick sections revealed an
      anomalous layer of material located at the epithelium-fiber interface, which was
      identified as a zone of liquefaction by TEM. Epithelial cells had minor
      structural defects but were not necrotic. Anterior portions of elongating and
      cortical fibers under the zone of liquefaction were undisrupted, whereas their
      posterior portions had numerous vacuoles. The anterior opacities were classified
      as anterior polar cataracts (APCs) based on the location and type of morphologic
      damage in the affected lenses. At twelve weeks postnatal, 25% of animals (3/12)
      had APCs that involved prominent vesiculation of the anterior cortex.
      Ultrastructural examination showed that large vesicles were located between and
      inside anterior fibers and that most extracellular spaces were abnormally
      widened. Posteriorly, internalization of the PSC by new fiber growth was
      disordered and displayed vesiculation and density variations. In the bow region,
      LM revealed minor structural irregularities that were identified as groups of
      apparently degenerating fibers by TEM. CONCLUSIONS: APCs in RCS rats are caused
      by degeneration of elongating fibers in the bow region and subsequent damage in
      the superficial anterior cortex. The percentage of animals with APCs (25%) was
      consistent with the percentage of animals in which mature cataracts eventually
      develop. The morphologic changes, time of onset, and percentage of animals
      affected suggest that APC is the initial manifestation of mature cataract
      formation in RCS rats.

PMID- 10067971
TI  - Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid
      peroxidation, and energy metabolism in diabetic precataractous lens.
AB  - PURPOSE: To evaluate changes in glutathione and NAD(P)-redox status, taurine and
      malondialdehyde (MDA) levels, glucose utilization, and energy metabolism in
      diabetic precataractous lenses and to assess whether these changes can be
      prevented with dietary taurine supplementation. METHODS: The experimental groups
      included control and streptozotocin-diabetic rats with a 3-week duration of
      diabetes fed unsupplemented or taurine (1% or 5%)-supplemented diets. The levels
      of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione (GSSG),
      glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides
      were assayed in individual lenses spectrofluorometrically by enzymatic methods,
      reduced glutathione (GSH) spectrofluorometrically with O-phthaldialdehyde, MDA
      colorimetrically with N-methyl-2-phenylindole, and taurine by high-performance
      liquid chromatography. Free cytosolic NAD+/NADH and NADP+/NADPH ratios were
      calculated from the lactate dehydrogenase and malic enzyme systems. RESULTS:
      Sorbitol pathway metabolites and MDA were increased, and GSH and taurine levels
      were reduced in diabetic rats versus controls. The profile of glycolytic
      intermediates (an increase in glucose 6-phosphate, no change in fructose 6
      phosphate and fructose 1,6-diphosphate, an increase in dihydroxyacetone
      phosphate, a decrease in 3-phosphoglycerate, phosphoenolpyruvate, and pyruvate,
      and no change in lactate), and a 9.2-fold increase in alpha-glycerophosphate
      suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+/NADH
      ratios, ATP levels, ATP/ADP, and adenylate charge were reduced, whereas free
      cytosolic NADP+/NADPH ratios were elevated. Lens taurine levels in diabetic rats
      were not affected by supplementation with 1% taurine. With 5% taurine
      supplementation, they were increased approximately 2.2-fold higher than those in
      untreated diabetics but remained 3.4-fold lower than in controls. Lens GSH levels
      were similar in diabetic rats fed unsupplemented and 5% taurine-supplemented
      diets, whereas GSSG and MDA levels and GSSG/GSH ratios were reduced by 5% taurine
      supplementation. The decrease in free cytosolic NAD+/NADH, ATP/ADP, and adenylate
      energy charge were ameliorated by 5% taurine supplementation, whereas
      accumulation of sorbitol pathway intermediates, depletion of myoinositol,
      inhibition of glycolysis, a decrease in ATP and total adenine nucleotide, and an
      increase in free cytosolic NADP+/NADPH were not prevented. CONCLUSIONS: Dietary
      taurine supplementation ameliorates MDA levels, GSSG/GSH, and NAD+/NADH and fails
      to prevent the osmotically mediated depletion of GSH and taurine and the decrease
      in glucose utilization and ATP levels in diabetic precataractous lens. Dietary
      taurine supplementation cannot be regarded as an alternative to aldose reductase
      inhibition in eliminating antioxidant and metabolic deficits contributing to
      diabetes-associated cataractogenesis.

PMID- 10067972
TI  - Role for nitric oxide in the hyperpermeability and hemodynamic changes induced by
      intravenous VEGF.
AB  - PURPOSE: To explore the effects of brief intravenous (IV) infusion of vascular
      endothelial growth factor (VEGF) on vascular albumin permeability, blood flow,
      and vascular conductance (blood flow normalized to arterial blood pressure) in
      ocular tissues and brain and to assess the role of nitric oxide in mediating
      these changes. METHODS: A quantitative, double-tracer, radiolabeled albumin
      permeation method was combined with radiolabeled microspheres for assessment of
      changes in vascular permeability and blood flow, respectively, induced in ocular
      tissues by IV infusion of recombinant human VEGF165 for 20 minutes (80-450
      picomoles/kg body weight). An inhibitor of nitric oxide synthase (NOS), NG
      monomethyl-L-arginine (L-NMMA; 50 micromoles/kg body weight infused
      simultaneously with VEGF), was used to explore the role of nitric oxide in
      mediating the vascular changes induced by VEGF. RESULTS: Infusion of VEGF165 in
      thiopental-anesthetized rats dose-dependently increased 125I albumin permeation
      in the retina, anterior uvea, and choroid/sclera and in brain, aorta, lung,
      kidney, small intestine, and peripheral nerve. Mean arterial blood pressure,
      cardiac output, and stroke volume were decreased only at the highest dose of
      VEGF, whereas heart rate remained unchanged. Blood flow was increased in the
      anterior uvea, and vascular conductance was increased in retina, anterior uvea,
      choroid/sclera, and brain at the highest dose of VEGF. The NOS inhibitor, L-NMMA,
      blocked VEGF-induced vascular hyperpermeability in all ocular and nonocular
      tissues, prevented the increase in vascular conductance in all ocular tissues,
      and blocked the decrease in mean arterial blood pressure, cardiac output, and
      stroke volume. Infusion of L-NMMA alone decreased vascular conductance in
      choroid/sclera and kidney, slightly increased mean arterial blood pressure, and
      in general, did not affect 125I-albumin permeation. (L-NMMA slightly decreased
      albumin permeation in the retina and increased it in the brain.) CONCLUSIONS:
      Intravenous infusion of VEGF can acutely impair endothelial cell barrier
      functional integrity and relax resistance arterioles in ocular tissues and brain
      through a mechanism involving activation of NOS.

PMID- 10067973
TI  - Polyol formation and NADPH-dependent reductases in dog retinal capillary
      pericytes and endothelial cells.
AB  - PURPOSE: Dogs fed a diet containing 30% galactose experience retinal vascular
      changes similar to those in human diabetic retinopathy, with selective pericyte
      loss as an initial lesion. In the present study the relationship among reduced
      nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductases, polyol
      formation, and flux through the polyol pathway in cultured dog retinal capillary
      cells were investigated. METHODS: Pericytes and endothelial cells were cultured
      from retina of beagle dogs. NADPH-dependent reductases were characterized by
      chromatofocusing after gel filtration. Sugars in cultured cells were analyzed by
      gas chromatography, and flux through the polyol pathway was investigated by 19F
      nuclear magnetic resonance (NMR) with 3-fluoro-3-deoxy-D-glucose (3FG) as a
      substrate. The presence of aldose reductase and sorbitol dehydrogenase in these
      cells was examined by northern blot analysis. RESULTS: Two distinct peaks
      corresponding to aldose reductase and aldehyde reductase, the latter being
      dominant, were observed in pericytes by chromatofocusing. Culture in medium
      containing either 10 mM D-galactose or 30 mM D-glucose resulted in the
      accumulation of sugar alcohol in pericytes that was markedly reduced by aldose
      reductase inhibitors. 19F NMR spectra obtained from pericytes cultured for 5 days
      in medium containing 2 mM 3FG displayed the marked accumulation of 3-fluoro
      deoxysorbitol but not 3-fluoro-deoxyfructose. No 3FG metabolism was observed in
      similarly cultured endothelial cells. With northern blot analysis, aldose
      reductase was detected in pericytes but not in endothelial cells. Sorbitol
      dehydrogenase was below the detectable limit in pericytes and endothelial cells.
      CONCLUSIONS: Aldose, aldehyde, and glyceraldehyde reductases are present in dog
      retinal capillary pericytes, with aldehyde reductase being the major reductase
      present. Polyol accumulation easily occurs in pericytes but not in endothelial
      cells.

PMID- 10067974
TI  - Expression of vitreous cytokines in proliferative vitreoretinopathy: a
      prospective study.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is a major cause of failure of
      retinal detachment surgery. It is believed to be a wound-healing process in the
      retina. Many of the cellular functions are influenced by cytokines and growth
      factors such as interleukins (ILs). The present study was conducted to
      investigate the presence of transforming growth factor-beta 2 (TGF-beta2), basic
      fibroblast growth factor (bFGF), IL-1beta, IL-6, and protein in the vitreous of
      patients with retinal detachment and to determine the value of these mediators in
      predicting the future development of PVR. METHODS: A prospective study was
      conducted in 140 consecutive patients with rhegmatogenous retinal detachment in
      whom vitrectomy was considered necessary. Vitreous samples were analyzed for the
      presence of TGF-beta2, bFGF, IL-1beta, IL-6, and protein. Patients were then
      followed up for 3 months for the development of postoperative PVR. RESULTS: The
      mean levels of TGF-beta2, bFGF, IL-1beta, and protein in the vitreous were
      significantly higher (P < 0.05) in patients with preoperative PVR compared with
      those without. The mean levels of TGF-beta2, bFGF, IL-6, and protein in the
      vitreous were significantly higher (P < 0.05) in patients who had postoperative
      PVR compared with those who did not. Multivariate logistic regression analysis
      showed IL-6 and protein to be significant (P < 0.05), independent, predictive
      risk factors for the development of PVR. CONCLUSIONS: The various cytokines may
      play a role in the pathobiology of PVR. High vitreous levels of IL-6 and protein
      were identified as significant risk factors for PVR. A model was developed to
      predict the probability of development of postoperative PVR in these patients,
      and it may be used to indicate intravitreal pharmacologic treatment for those at
      risk.

PMID- 10067975
TI  - Necrosis and apoptosis after retinal ischemia: involvement of NMDA-mediated
      excitotoxicity and p53.
AB  - PURPOSE: Accumulated evidence has shown that apoptosis and necrosis contribute to
      neuronal death after ischemia. The present study was performed to study the
      temporal and spatial patterns of neuronal necrosis and apoptosis after ischemia
      in retina and to outline mechanisms underlying necrosis and apoptosis. METHODS:
      Retinal ischemia was induced by increasing intraocular pressure to a range of 160
      mm Hg to 180 mm Hg for 90 minutes in adult rats. The patterns of neuronal cell
      death were determined using light and electron microscopy and were visualized by
      TdT-dUTP nick-end labeling (TUNEL). The mRNA expression profile of p53 was
      examined using reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization histochemistry. Immunohistochemistry was performed using anti
      p53, anti-microtubule associated protein-2, and anti-glial fibrillary acidic
      protein antibodies. RESULTS: Within 4 hours after ischemia, neurons in the inner
      nuclear cell layer (INL) and ganglion cell layer (GCL) underwent marked necrosis,
      made apparent by swelling of the cell body and mitochondria, early fenestration
      of the plasma membrane, and irregularly scattered condensation of nuclear
      chromatin. After 3 days, the INL and GCL neurons showed further degeneration
      through apoptosis marked by cell body shrinkage, aggregation, and condensation of
      nuclear chromatin. Apoptotic neurons were also observed sparsely in the outer
      nuclear cell layer. Intravitreal injections of MK-801 prevented early neuronal
      degeneration after ischemia. Of note, mRNA and protein levels of p53, the tumor
      suppressor gene known to induce apoptosis, were increased in the retinal areas
      undergoing apoptosis 1 to 3 days after ischemic injury. CONCLUSIONS: Ischemia
      produces the N-methyl-D-aspartate-mediated necrosis and slowly evolving apoptosis
      of neurons in the retina. The latter may depend on the expression of the p53
      proapoptosis gene.

PMID- 10067976
TI  - Angiotensin II-induced constrictions are masked by bovine retinal vessels.
AB  - PURPOSE: To unmask the vasoconstricting effect of angiotensin II (Ang II) on
      retinal smooth muscle by studying its interaction with endothelium-derived
      paracrine substances. This study focused specifically on determining the changes
      in vascular diameter and the release of endothelial-derived vasodilators, nitric
      oxide (NO) and prostaglandin (PG) I2, from isolated retinal microvessels.
      METHODS: Bovine retinal central artery and vein were cannulated, and arterioles
      and venules were perfused with oxygenated/heparinized physiological salt solution
      at 37 degrees C. This ex vivo perfused retinal microcirculation model was used to
      observe the contractile effects of Ang II on arterioles and venules of different
      diameters. The NO and PGI2 synthase inhibitors, 1-NOARG and flurbiprofen,
      respectively, were used to unmask Ang II vasoconstriction; the changes in
      vascular diameters were then measured. Enzyme immunoassays were used to measure
      the release of cGMP (an index of NO release) and 6-keto-PG-F1alpha (a stable
      metabolite of PGI2) from isolated bovine retinal vessels. RESULTS: Topically
      applied Ang II (10(-10) M to 10(-4) M) caused significant (P < 0.05) arteriolar
      and venular constrictions in a dose-dependent manner, with the smallest retinal
      arterioles (7+/-0.2 microm luminal diameter) and venules (12+/-2 microm luminal
      diameter) significantly more sensitive than larger vessels. After the inhibition
      of endogenous NO and PGI2 synthesis by 1-NOARG and flurbiprofen, respectively,
      the vasoconstriction effects of Ang II became more pronounced. Again, the
      smallest vessels tested were significantly more sensitive, and synthesis of
      endothelial-derived relaxing factor (EDRF), therefore, may be most important in
      these vessels. Vasoactive doses of Ang II (10(-10) M to 10(-4) M) caused a dose
      dependent increase in the release of NO and PGI2 from isolated bovine retinal
      vessels, indicating that the increase in EDRF may nullify direct Ang II-induced
      vasoconstriction. Interestingly, intraluminal administration of Ang II caused
      only vasodilation. CONCLUSIONS: This study demonstrates that the retinal vascular
      endothelium acts as a buffer against the vasoconstricting agent Ang II via
      release of vasodilators NO and PGI2, and the vasoconstriction effects due to Ang
      II are most prominent in the smallest diameter vessels.

PMID- 10067977
TI  - Riluzole improves functional recovery after ischemia in the rat retina.
AB  - PURPOSE: Retinal ischemia leads to neuronal death. The effects of riluzole, a
      drug that protects against the deleterious effect of cerebral ischemia by acting
      on several types of ion channels and blocking glutamatergic neurotransmission,
      were investigated in a rat model of retinal ischemic injury. METHODS: Retinal
      ischemia was induced by increasing intraocular pressure above systolic blood
      pressure for 30 minutes. Electroretinograms were recorded before ischemia and at
      different periods of reperfusion. Riluzole was injected or topically applied to
      the eye before or after ischemia and twice daily during the reperfusion period.
      Retinas were harvested for histopathology (toluidine blue and silver-impregnation
      stainings, Tdt-dUTP terminal nick-end labeling [TUNEL] method) and
      immunohistochemistry for cytoskeletal glial fibrillary acid protein and c-jun NH2
      terminal kinase (p-JNK). RESULTS: Ischemia for 30 minutes caused a reduction of a
      and b-waves of the electroretinogram. Systemic and topical treatments with
      riluzole significantly enhanced the recovery of the reduced a- and b-waves after
      defined reperfusion times. Riluzole also prevented or attenuated ischemia-induced
      retinal cell death (necrosis and apoptosis) and reduced the activation of p-JNK,
      c-jun phosphorylation, and the increase of cytoskeletal proteins induced by
      ischemic injury. CONCLUSIONS: Riluzole acted in vivo as a potent neuroprotective
      agent against pressure-induced ischemia. Therefore, riluzole may be a major drug
      for use in protection against retinal injury.

PMID- 10067978
TI  - Inhibition of lysosomal degradative functions in RPE cells by a retinoid
      component of lipofuscin.
AB  - PURPOSE: To investigate the effect of the lipofuscin component N-retinylidene-N
      retinylethanolamine (A2-E) on degradative functions of lysosomes in human retinal
      pigment epithelial (RPE) cells and to evaluate its mechanism of action. METHODS:
      A2-E was coupled to low-density lipoprotein (LDL). Human RPE cell cultures were
      loaded with the A2-E/LDL complex, and controls were run with medium containing
      LDL alone. To determine whether A2-E accumulated in lysosomes, cells were
      fractionated in a Percoll gradient, and protein degradation was determined by
      metabolic labeling and measurement of the release of low-molecular-weight
      radioactivity. Lysosomal degradation was distinguished from nonlysosomal
      degradation by inclusion of NH4Cl in the medium. The metabolism of sulfated
      glycosaminoglycans was studied by radiosulfate incorporation in pulse-chase
      experiments. Intralysosomal pH was determined using a fluorescent lysosomotropic
      pH indicator. RESULTS: A2-E accumulated almost exclusively in the lysosomal
      compartment. Lysosomal protein degradation was reduced in a dose-dependent
      fashion in A2-E-treated cells. The selectivity of A2-E on lysosomal function was
      demonstrated by its lack of effect on degradation of extralysosomal protein.
      Lysosomal glycosaminoglycan catabolism of RPE cells was also strongly inhibited
      by A2-E. Lysosomal pH was increased by A2-E. CONCLUSIONS: The findings indicate
      that accumulation of A2-E in RPE cells interferes with lysosomal functions as
      exemplified by its inhibitory effect on protein and glycosaminoglycan catabolic
      pathways. The quaternary amine character of the A2-E apparently causes a
      perturbation of the acidic intralysosomal milieu, resulting in diminished
      hydrolase action and consequent accumulation of undegraded material. Such
      mechanism could be operative in retinal diseases associated with excessive
      lipofuscin accumulation including age-related macular degeneration.

PMID- 10067979
TI  - Expression of antioxidant protective proteins in the rat retina during prenatal
      and postnatal development.
AB  - PURPOSE: In retinopathy of prematurity, capillary growth in the retina is
      attenuated. Subsequent cyclic elevation of oxygen levels leads to renewed
      capillary growth that may eventually result in retinal detachment. It is
      hypothesized that the sensitivity of the premature retina to oxidative shock
      results from the absence of antioxidant protective proteins. METHODS: The
      expression of heme oxygenase-1, metallothionein, superoxide dismutase, and
      catalase mRNAs was measured in retinas of rats from 6 days before birth to 4 days
      after birth using in situ hybridization and semiquantitative reverse
      transcription-polymerase chain reaction with Southern blot analysis. RESULTS:
      Superoxide dismutase mRNA was expressed to a similar extent at all time points.
      Metallothionein mRNA expression, which was high at embryonic days (E) 16 and 18,
      decreased to low levels by the time of birth and remained low at least until 4
      days after birth. Catalase mRNA expression was low until birth and increased
      until at least postnatal day 4. Heme oxygenase-1 mRNA showed low expression at
      E16 and E18, increased before birth, and then diminished. CONCLUSIONS: Four
      antioxidant protein mRNAs showed very different patterns of expression in the rat
      retina. Two of these proteins, heme oxygenase-1 and catalase, were expressed at
      relatively low levels until approximately the time of birth. The former is
      important in protection against heme-mediated generation of reactive oxygen
      species, whereas the latter protects against hydrogen peroxide-generated damage.
      As a result of the low expression of these mRNAs, and presumably the proteins
      encoded by them, the premature rat (and probably the premature human) is likely
      to be born without a full complement of antioxidant defenses.

PMID- 10067980
TI  - Human Muller cells express VEGF183, a novel spliced variant of vascular
      endothelial growth factor.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor
      expressed as multiple RNA transcripts due to alternative splicing. During an
      investigation of the expression of VEGF mRNA in human Muller cells cultured under
      hypoxic conditions, a cDNA species was isolated whose size was incompatible with
      known VEGF transcripts. This study was performed to determine the nucleotide
      sequence of the candidate VEGF species and examine the effects of hypoxia on its
      expression. METHODS: Cultured human Muller cells were exposed to normoxic (20%
      O2, 5% CO2, 75% N2) or hypoxic (2% O2, 5% CO2, 93% N2) conditions at 37 degrees C
      for 4 hours and processed for reverse transcription-polymerase chain reaction (RT
      PCR), molecular cloning, Southern hybridization, nucleotide sequencing,
      semiquantitative RT-PCR, and ribonuclease protection assay. RESULTS: The
      nucleotide sequence of the novel VEGF species isolated from human Muller cells
      had a short exon 6-encoded sequence without 18-bp nucleotides immediately
      upstream of the exon 7-encoded sequence in VEGF189. The 18-bp deletion
      (corresponding to the six amino acids Tyr-Lys-Ser-Trp-Ser-Val) was compatible
      with a polypeptide containing 183 amino acids (VEGF183). Although VEGF183 mRNA
      was found in all tissues studied, its expression seemed to be higher than that of
      VEGF 189 in the brain and spleen; lower in the kidney, retina, skeletal muscle,
      and liver; and at similar level in the heart. Exposure to hypoxic conditions for
      4 hours promoted increased levels of VEGF mRNA including that of VEGF183.
      CONCLUSIONS: The expression of the novel isoform VEGF 183 in human Muller cells,
      its variable tissue expression, and its modulation by hypoxia may provide another
      pathway for VEGF induction of angiogenesis in the retina.

PMID- 10067981
TI  - CNTF, not other trophic factors, promotes axonal regeneration of axotomized
      retinal ganglion cells in adult hamsters.
AB  - PURPOSE: To investigate the in vivo effects of trophic factors on the axonal
      regeneration of axotomized retinal ganglion cells in adult hamsters. METHODS: The
      left optic nerve was transected intracranially or intraorbitally, and a
      peripheral nerve graft was apposed or sutured to the axotomized optic nerve to
      enhance regeneration. Trophic factors were applied intravitreally every 5 days.
      Animals were allowed to survive for 3 or 4 weeks. Regenerating retinal ganglion
      cells (RGCs) were labeled by applying the dye Fluoro-Gold to the distal end of
      the peripheral nerve graft 3 days before the animals were killed. RESULTS:
      Intravitreal application of ciliary neurotrophic factor substantially enhanced
      the regeneration of damaged axons into a sciatic nerve graft in both experimental
      conditions (intracranial and intraorbital optic nerve transections) but did not
      increase the survival of distally axotomized RGCs. Basic fibroblast growth factor
      and neurotrophins such as nerve growth factor, brain-derived neurotrophic factor,
      neurotrophin-3, and neurotrophin-4/5 failed to enhance axonal regeneration of
      distally axotomized RGCs. CONCLUSIONS: Neurons of the adult central nervous
      system can regenerate in response to trophic supply after injury, and ciliary
      neurotrophic factor is at least one of the trophic factors that can promote
      axonal regeneration of axotomized RGCs.

PMID- 10067982
TI  - Repopulation of different layers of host human Bruch's membrane by retinal
      pigment epithelial cell grafts.
AB  - PURPOSE: To determine the morphology of human retinal pigment epithelium (RPE)
      after reattachment to different ultrastructural layers of human Bruch's membrane
      (BM). METHODS: Bruch's membrane explants were prepared from eyes of 23 human
      donors (age range, 11-89 years). The basal lamina of the RPE, inner collagenous
      layer, and elastin layer were removed sequentially by mechanical and enzymatic
      techniques. First-passage cells of human RPE (15,000 cells/6 mm explant) from
      three donors (ages, 52, 64, and 80 years) were plated onto different layers of
      human BM, and the explants were examined by scanning and transmission electron
      microscopy up to 21 days later. RESULTS: RPE flattened and extended footplates 6
      hours after plating onto basal lamina. Cells remained round 6 and 24 hours after
      plating onto the inner collagenous, elastin, or outer collagenous layer. The RPE
      cells became confluent 14 days after plating onto basal lamina but did not become
      confluent up to 21 days after plating onto the inner collagenous or elastin
      layer. Sparse round cells were observed 21 days after plating onto deeper layers,
      suggesting extensive loss of RPE. CONCLUSIONS: The morphology and subsequent
      behavior of the RPE reattached to BM depends on the anatomic layer of BM
      available for cell reattachment. The results suggest that the ability of
      transplanted RPE to repopulate BM in age-related macular degeneration and other
      disorders may depend on the layer of BM available to serve as a substrate for
      cell reattachment.

PMID- 10067983
TI  - Increase in the advanced glycation end product pentosidine in Bruch's membrane
      with age.
AB  - PURPOSE: To determine whether there is an age-related increase of pentosidine in
      human Bruch's membranes and to localize pentosidine and carboxymethyllysine
      (CML), two well-characterized, advanced glycation end products (AGEs) in aged
      human Bruch's membranes and choroid in vivo. METHODS: Human Bruch's membrane
      samples were isolated from the retinal pigment epithelium (RPE) and choroid and
      subjected to reversed-phase high-performance liquid chromatography to determine
      pentosidine content. A polyclonal anti-pentosidine antibody and a monoclonal
      antibody specific for carboxymethyllysine were used to localize AGEs in 20-month
      old nondiabetic, 82-year-old nondiabetic, and 82-year-old diabetic globes.
      RESULTS: Human Bruch's membranes (n = 20) showed a linear age-dependent increase
      in pentosidine that reached approximately 0.17 millimoles pentosidine per mole
      hydroxyproline in late life (r = 0.896; P < 0.001). Immunohistochemical
      evaluation showed evidence of pentosidine in Bruch's membrane, choroidal
      extracellular matrix, and vessel walls in the 82-year-old nondiabetic and
      diabetic globes. A similar staining pattern was found with the anti-CML antibody.
      Basal laminar deposits and drusen stained with both antibodies in the elderly
      nondiabetic eye. In contrast, neither antibody stained the 20-month-old tissue.
      CONCLUSIONS: We provide biochemical and immunohistochemical evidence for the
      formation of pentosidine and CML structures in human Bruch's membrane and choroid
      with age. These changes could promote aging of the RPE-Bruch's membrane-choroid
      complex.

PMID- 10067984
TI  - Analysis of p16 (CDKN2/MTS-1/INK4A) alterations in primary sporadic uveal
      melanoma.
AB  - PURPOSE: To define more clearly the role of the tumor suppressor gene p16 in
      uveal melanoma by determining the relative contribution of all known mechanisms
      of p16 inactivation in this tumor. METHODS: A comprehensive genetic analysis of
      the p16 gene was performed in 33 primary sporadic ciliochoroidal and choroidal
      melanomas. Fourteen highly polymorphic microsatellite markers surrounding the p16
      locus on chromosome 9p21 were used for the microsatellite analysis. Sequence
      analysis of the p16 gene was performed on those tumors with 9p21 loss of
      heterozygosity. To investigate methylation as an alternative mechanism of
      inactivation of p16, methylation-specific polymerase chain reaction was performed
      on all tumor DNA samples. RESULTS: Loss of heterozygosity (LOH) was found in 8 of
      33 (24%) uveal melanomas. No evidence of a second region of LOH that did not
      include the p16 locus was found. Four cases had hemizygous losses including
      markers both distal and proximal to p16. Homozygous deletion of the p16 gene was
      detected in the 4 remaining cases by microsatellite analysis. Sequence analysis
      revealed no p16 mutations in the tumors with hemizygous loss of p16. Methylation
      of the 5' CpG island of p16 was found in one tumor with 9p21 LOH and in another
      without LOH. CONCLUSIONS: p16 inactivation by HD or methylation occurs in 27% of
      uveal melanomas, representing the most common molecular genetic alteration
      identified thus far in uveal melanoma.

PMID- 10067985
TI  - Regulation of gelatinase B production in corneal cells is independent of
      autocrine IL-1alpha.
AB  - PURPOSE: The matrix metalloproteinase gelatinase B is synthesized by cells at the
      leading edge of the corneal epithelium migrating to heal a wound. Recent data
      from the authors' laboratory suggest that excessive synthesis contributes to
      repair defects. The goal of the study reported here was to investigate mechanisms
      controlling gelatinase B production by corneal epithelial cells. METHODS: Freshly
      isolated cultures of corneal epithelial cells and early passage stromal
      fibroblasts from rabbit were used for these studies. RESULTS: In a previous
      study, it was found that the cytokine interleukin (IL)-1alpha is released into
      the culture medium of corneal epithelial cells more efficiently when they are
      plated at low density with limited cell-cell contact than when plated at high
      density. In this study, we show that production of gelatinase B by these cells is
      similarly affected by cell plating density. However, it is further demonstrated
      that these two events are not dependent on one another but occur in parallel: IL
      1alpha does not regulate gelatinase B production (synthesis), nor was there
      evidence that any other secreted autocrine cytokine acts as mediator. Instead,
      our data suggest that gelatinase B production is downregulated directly by high
      cell density and indicate a connection to the level of protein kinase C activity.
      Nevertheless, the anticancer agent suramin, which blocks collagenase synthesis by
      interfering with autocrine cytokine-receptor interactions, still inhibits
      synthesis of gelatinase B. CONCLUSIONS: Unlike collagenase synthesis by corneal
      stromal fibroblasts, production (synthesis) of gelatinase B does not appear to be
      controlled by secreted autocrine cytokines but can still be inhibited by suramin.
      Suramin may make an effective therapeutic agent for controlling pathologic
      overproduction of gelatinase B in corneal ulcers.

PMID- 10067986
TI  - PAF binding to a single receptor in corneal epithelium plasma membrane.
AB  - PURPOSE: To study the binding characteristics and the expression of platelet
      activating factor receptors (PAF-R) in corneal epithelium to elucidate the site
      of action of PAF. METHODS: Binding of [3H]PAF was investigated in subcellular
      fractions of the epithelia of bovine corneas and in membranes from cultured
      rabbit corneal epithelial cells. Dose-response inhibition curves of [3H]PAF
      specific binding were generated using increasing concentrations of several PAF-R
      antagonists. RNA from rabbit corneal epithelial cells was probed for PAF-R
      expression by reverse transcription-polymerase chain reaction (RT-PCR) with
      specifically designed degenerated primers. RESULTS: Scatchard analysis showed a
      high-affinity binding site in bovine and rabbit corneal epithelium. The
      dissociation constant (Kd) and the maximum binding sites (Bmax) in a bovine
      membrane preparation and similar rabbit fraction were 0.77+/-0.03 nM and 180+/-21
      femtomoles/mg protein and 4.3 nM and 1.3 picomoles/mg protein, respectively.
      Specific PAF-binding sites were found in bovine preparations enriched in plasma
      membranes with a Kd = 69.6 pM and Bmax = 80 femtomoles/mg protein; no specific
      binding was found in nuclei or microsomal fractions. RT-PCR of rabbit corneal
      epithelium generated a single product of the predicted size (478 bp). The deduced
      amino acid sequence of the purified PCR product was 87% homologous to human PAF
      R. The hetrazepines BN 50727 and BN 50730 and the PAF structural analogues CV
      3988 and CV 6209 competitively inhibited [3H]PAF binding to corneal epithelium
      with similar potency. WEB 2086 BS was two orders of magnitude less active in
      antagonizing PAF binding. CONCLUSIONS: Corneal epithelium contains a single
      population of receptors localized in the plasma membrane. PAF antagonists exert
      their actions by blocking this PAF-R. The partial sequence deduced in rabbit
      corneal PAF-R show a higher homology to the human PAF-R.

PMID- 10067987
TI  - Brightness alters Heidelberg retinal flowmeter measurements in an in vitro model.
AB  - PURPOSE: The Heidelberg Retinal Flowmeter (HRF), a laser Doppler flowmetry
      device, has captured interest as a research and clinical tool for measurement of
      ocular blood flow. Concerns remain about the range and accuracy of the values
      that it reports. METHODS: An in vitro blood-flow model was constructed to provide
      well-controlled laminar flow through a glass capillary for assessment by HRF. A
      change in material behind the glass capillary was used to simulate changing
      brightness conditions between eyes. RESULTS: Velocities reported by the HRF
      correlated linearly to true velocities below 8.8 mm/sec. Beyond 8.8 mm/sec, HRF
      readings fluctuated randomly. True velocity and HRF reported velocities were
      highly correlated, with r = 0.967 (P < 0.001) from 0.0 mm/sec to 2.7 mm/sec mean
      velocity using a light background, and r = 0.900 (P < 0.001) from 2.7 mm/sec to
      8.8 mm/sec using a darker background. However, a large change in the y-intercept
      occurred in the calibration curve with the background change. CONCLUSIONS: The
      HRF may report velocities inaccurately because of varying brightness in the
      fundus. In the present experiment, a darker background produced an overreporting
      of velocities. An offset, possibly introduced by a noise correction routine,
      apparently contributed to the inaccuracies of the HRF measurements. Such offsets
      vary with local and global brightness. Therefore, HRF measurements may be error
      prone when comparing eyes. When used to track perfusion in a single eye over
      time, meaningful comparison may be possible if meticulous care is taken to align
      vessels and intensity controls to achieve a similar level of noise correction
      between measurements.

PMID- 10067988
TI  - Analysis of blood flow in the long posterior ciliary artery of the cat.
AB  - PURPOSE: Experiments were undertaken to use a new technique for direct on-line
      measurement of blood flow in the long posterior ciliary artery (LPCA) in cats and
      to evaluate possible physiological mechanisms controlling blood flow in the
      vascular beds perfused by this artery. METHODS: Blood flow in the temporal LPCA
      was measured on a continuous basis using ultrasonic flowmetry in anesthetized
      cats. Effects of acute sectioning of the sympathetic nerve and changes in LPCA
      and cerebral blood flows in response to altered levels of inspired CO2 and O2
      were tested in some animals. In others, the presence of vascular autoregulatory
      mechanisms in response to stepwise elevations of intraocular pressure was
      studied. RESULTS: Blood flow in the temporal LPCA averaged 0.58+/-0.03 ml/min in
      45 cats anesthetized with pentobarbital. Basal LPCA blood flow was not altered by
      acute sectioning of the sympathetic nerve or by changes in low levels of inspired
      CO2 and O2, although 10% CO2 caused a modest increase. Stepwise elevations of
      intraocular pressure resulted in comparable stepwise decreases of LPCA blood
      flow, with perfusion pressure declining in a linear manner throughout the
      perfusion-pressure range. CONCLUSIONS: Ultrasonic flowmetry seems to be a useful
      tool for continuous on-line measurement of LPCA blood flow in the cat eye. Blood
      flow to vascular beds perfused by this artery does not seem to be under
      sympathetic neural control and is refractory to modest alterations of blood gas
      levels of CO2 and O2. Blood vessels perfused by the LPCA show no clear
      autoregulatory mechanisms.

PMID- 10067989
TI  - Metabolic acidosis-induced retinopathy in the neonatal rat.
AB  - PURPOSE: Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat,
      analogous to human retinopathy of prematurity (ROP), was previously described by
      our group. In this model, it is possible that CO2-associated acidosis provides a
      biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis
      on the developing retinal vasculature of the neonatal rat was investigated.
      METHODS: A preliminary study of arterial blood pH was performed to confirm
      acidosis in our model. In neonatal rats with preplaced left carotid artery
      catheters, acute blood gas samples were taken 1 to 24 hours after gavage with
      either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal
      retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25
      and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100
      g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of
      recovery, rats were killed, and retinal vasculature was assessed using
      fluorescein perfusion and ADPase staining techniques. RESULTS: In the preliminary
      pH study, the minimum pH after NH4Cl gavage was 7.10+/-0.10 at 3 hours (versus
      7.37+/-0.03 in controls, mean +/- SD, P < 0.01). In the formal retinopathy study,
      preretinal neovascularization occurred in 36% of acidotic rats versus 5% of
      controls (P < 0.001). Acidotic rats showed growth retardation (final weight
      16.5+/-3.0 g versus 20.2+/-2.6 g, P < 0.001). The ratio of vascularized to total
      retinal area was smaller in acidotic rats (94%+/-4% versus 96%+/-2%, P < 0.001).
      CONCLUSIONS: Metabolic acidosis alone induces neovascularization similar to ROP
      in the neonatal rat. This suggests a possible biochemical mechanism by which high
      levels of CO2 induce neovascularization and supports the suggestion that acidosis
      may be an independent risk factor for ROP.

PMID- 10067990
TI  - Human diabetic neovascular membranes contain high levels of urokinase and
      metalloproteinase enzymes.
AB  - PURPOSE: Retinal neovascularization is one of the leading causes of blindness. A
      crucial event in this process is the remodeling and penetration of the capillary
      basement membrane by migrating endothelial cells. This process requires
      proteolysis of basement membrane components by a variety of proteinases. The
      objective of the present study was to determine the expression of proteinases in
      human retinal tissues showing active neovascularization. METHODS: Epiretinal
      neovascular membranes surgically removed from patients with proliferative
      diabetic retinopathy were analyzed by zymography, and the types and amounts of
      proteinases present in the tissues were determined. Retinas from nondiabetic
      donor eyes served as control specimens. RESULTS: Both the high- (54 kDa) and low-
      (33 kDa) molecular-weight forms of urokinase were present at significantly higher
      levels in neovascular membranes than in normal retinas. The pro forms of the
      matrix metalloproteinases (MMP) MMP-2 and MMP-9 were significantly elevated in
      the neovascular membranes in comparison with levels in normal retinas. In
      addition, the active forms of these enzymes were present in the membranes,
      whereas there was no detectable level of the active forms in normal retinas.
      CONCLUSIONS: Human diabetic neovascular membranes contain high levels of
      urokinase and MMP. The increased activity of proteinases in the final common
      pathway of retinal neovascularization indicates that inhibition of these enzymes
      may be a useful therapeutic target as an alternative approach in the management
      of proliferative retinopathies.

PMID- 10067991
TI  - Pilocarpine toxicity in retinal ganglion cells.
AB  - PURPOSE: Muscarinic agents reduce intraocular pressure by enhancing aqueous
      outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine
      is a well characterized neurotoxin and is widely used to generate animal seizure
      models. It was therefore investigated whether pilocarpine was also toxic to
      retinal ganglion cells. METHODS: Dissociated whole retinal preparations were
      prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been
      previously back-labeled with a fluorescent tracer. Retinal cells were incubated
      with pilocarpine, lithium, and inositol derivatives, and viability of the
      retrogradely labeled retinal ganglion cells was assayed after 24 hours. RESULTS:
      Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This
      toxicity was potentiated by lithium and blocked by epi- and myo-inositol.
      CONCLUSIONS: Pilocarpine is toxic to retinal ganglion cells in a mixed culture
      assay. This toxicity appears to depend on the inositol pathway and is similar to
      its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest
      concentration that did not affect ganglion cell survival) is roughly 1000-fold
      higher than the vitreal concentration and 20-fold higher than the scleral
      concentration that can be obtained with topical administration of 2% pilocarpine
      in the rabbit eye.

PMID- 10067992
TI  - The role of the orthopaedic surgeon in metastatic disease of the appendicular
      skeleton. Working Party on Metastatic Bone Disease in Breast Cancer in the UK.

PMID- 10067993
TI  - Trauma and orthopaedic surgery on the Internet.

PMID- 10067994
TI  - Longitudinal limb deficiencies and the sclerotomes. An analysis of 378 dysmelic
      malformations induced by thalidomide.
AB  - The pathogenesis of longitudinal reduction deformities of the limbs, or dysmelia,
      is still a matter of debate. Their morphological pattern was defined from a large
      collection of radiographs of children with dysmelia following the thalidomide
      disaster. We compared radiographs of 378 of these limbs with the sclerotomes
      which are areas of segmental sensory innervation of the limb skeleton defined by
      the radiation of referred pain. The pattern of dysmelia matched the sclerotomes
      closely in 279 limbs (73.5%). The principles of skeletal reduction in dysmelia
      are explained by the arrangement of the sclerotomes. The congruence between two
      separate and independent data sets shows that both patterns are expressions of
      the underlying segmental sensory innervation of the skeleton, and that the
      sensory nervous system is involved in the process of limb morphogenesis and
      teratogenesis.

PMID- 10067995
TI  - Radiolucent lines and component stability in knee arthroplasty. Standard versus
      fluoroscopically-assisted radiographs.
AB  - The radiolucent lines and the stability of the components of 66 knee
      arthroplasties were assessed by six orthopaedic surgeons on conventional
      anteroposterior and lateral radiographs and on fluoroscopic views which had been
      taken on the same day. The examiners were blinded as to the patients and clinical
      results. The interpretation of the radiographs was repeated after five months. On
      fluoroscopically-assisted radiographs four of the six examiners identified
      significantly more radiolucent lines for the femoral component (p < 0.05) and one
      significantly more for the tibial implant. Five examiners rated more femoral
      components as radiologically loose on fluoroscopically-assisted radiographs (p =
      0.0008 to 0.0154), but none did so for the tibial components. The mean intra- and
      interobserver kappa values were higher for fluoroscopically-assisted radiographs
      for both components. We have shown that fluoroscopically-assisted radiographs
      allow more reproducible, and therefore reliable, detection of radiolucent lines
      in total knee arthroplasty. Assessment of the stability of the components is
      significantly influenced by the radiological technique used. Conventional
      radiographs are not adequate for evaluation of the stability of total knee
      arthroplasty and should be replaced by fluoroscopically-assisted films.

PMID- 10067996
TI  - Manipulation of total knee replacements. Is the flexion gained retained?
AB  - As part of a prospective study of 476 total knee replacements (TKR), we evaluated
      the use of manipulation under anaesthesia in 47 knees. Manipulation was
      considered when intensive physiotherapy failed to increase flexion to more than
      80 degrees. The mean time from arthroplasty to manipulation was 11.3 weeks
      (median 9, range 2 to 41). The mean active flexion before manipulation was 62
      degrees (35 to 80). One year later the mean gain was 33 degrees (Wilcoxon signed
      rank test, range -5 to 70, 95% CI 28.5 to 38.5). Definite sustained gains in
      flexion were achieved even when manipulation was performed four or more months
      after arthroplasty (paired t-test, p < 0.01, CI 8.4 to 31.4). A further 21
      patients who met our criteria for manipulation declined the procedure. Despite
      continued physiotherapy, there was no significant increase in flexion in their
      knees. Six weeks to one year after TKR, the mean change was 3.1 degrees (paired t
      test, p = 0.23, CI -8.1 to +2).

PMID- 10067997
TI  - The tourniquet in total knee arthroplasty. A prospective, randomised study.
AB  - We assessed the influence of the use of a tourniquet in total knee arthroplasty
      in a prospective, randomised study. After satisfying exclusion criteria, we
      divided 77 patients into two groups, one to undergo surgery with a tourniquet and
      one without. Both groups were well matched. The mean change in knee flexion in
      the group that had surgery without a tourniquet was significantly better at one
      week (p = 0.03) than in the other group, but movement was similar at six weeks
      and at four months. There was no significant difference in the surgical time,
      postoperative pain, need for analgesia, the volume collected in the drains,
      postoperative swelling, and the incidence of wound complications or of deep
      venous thrombosis. We conclude that the use of a tourniquet is safe and that
      current practice can be continued.

PMID- 10067998
TI  - Extensive post-traumatic ossification of the patellar tendon. A report of two
      cases.
AB  - Two men, aged 21 and 50 years, were seen with ossification of the patellar tendon
      after injury to the knee in adolescence. They complained of pain and had patella
      alta. Large bony masses were excised from below the affected patellae. The
      patellar tendon was then reconstructed using a Leeds-Keio ligament. The results
      at six and ten years, respectively, were good, with neither patient having pain
      or an extension lag.

PMID- 10067999
TI  - Meniscal movement. An in-vivo study using dynamic MRI.
AB  - We present the first study in vivo of meniscal movement in normal knees under
      load. Using an open MR scanner, allowing imaging in physiological positions in
      near to real-time, 16 young footballers were scanned moving from full extension
      to 90 degrees flexion in the sagittal and coronal planes. Excursion of the
      meniscal horns, radial displacement and meniscal height were measured. On weight
      bearing, the anterior horn of the medial meniscus moves through a mean of 7.1 mm
      and the posterior horn through 3.9 mm, with 3.6 mm of mediolateral radial
      displacement. The height of the anterior horn increases by 2.6 mm and that of the
      posterior horn by 2.0 mm. The anterior horn of the lateral meniscus moves 9.5 mm
      and the posterior horn 5.6 mm, with 3.7 mm of radial displacement. The height of
      the anterior horn increases by 4.0 mm, and that of the posterior horn by 2.4 mm.
      In non-weight-bearing, the anterior horn of the medial meniscus moves 5.4 mm and
      the posterior horn 3.8 mm, with 3.3 mm of radial displacement. The anterior horn
      of the lateral meniscus moves 6.3 mm, and the posterior horn 4.0 mm, with 3.4 mm
      of radial displacement. The most significant differences between weight-bearing
      and non-weight-bearing were the movement and vertical height of the anterior horn
      of the lateral meniscus.

PMID- 10068000
TI  - Is revision as good as primary hip replacement? A comparison of quality of life.
AB  - Primary total hip arthroplasty (THA) is one of the most effective ways of
      improving quality of life (QoL). We have compared the improvement in QoL in 62
      patients who had a cemented revision of a THA with that of 62 primary
      replacements. One year after operation the median QoL score had been
      significantly improved in both groups; from 0.870 to 0.990 in the primary group
      (p < 0.0001) and from 0.870 to 0.980 in the revised group (p < 0.0001). There was
      no significant difference in the improvement in scores between the groups (p =
      0.29). When reviewed after four years there was no difference in the pain score
      for either group (p = 0.89), but that for function had deteriorated
      significantly. This was associated with revision surgery (p = 0.018) and a low
      preoperative QoL score (p = 0.004). We conclude that both primary and revision
      operations give a significant improvement in the QoL but function after revision
      may be less durable than after a primary arthroplasty.

PMID- 10068001
TI  - Analysis of 118 second-generation metal-on-metal retrieved hip implants.
AB  - Osteolysis is due to particulate wear debris and is responsible for the long-term
      failure of total hip replacements. It has stimulated the development of
      alternative joint surfaces such as metal-on-metal or ceramic-on-ceramic implants.
      Since 1988 the second-generation metal-on-metal implant Metasul has been used in
      over 60 000 hips. Analysis of 118 retrieved specimens of the head or cup showed
      rates of wear of approximately 25 microm for the whole articulation per year in
      the first year, decreasing to about 5 microm per year after the third. Metal
      surfaces have a 'self-polishing' capacity. Scratches are worn out by further
      joint movement. Volumetric wear was decreased some 60-fold compared with that of
      metal-on-polyethylene implants, suggesting that second-generation metal-on-metal
      prostheses may considerably reduce osteolysis.

PMID- 10068002
TI  - Migration of the Duraloc cup at two years.
AB  - We carried out 71 primary total hip arthroplasties using porous-coated,
      hemispherical press-fit Duraloc '100 Series' cups in 68 consecutive patients; 61
      were combined with the cementless Spotorno stem and ten with the cemented Lubinus
      SP II stem. Under-reaming of 2 mm achieved a press-fit. Of the 71 hips, 69
      (97.1%) were followed up after a mean of 2.4 years. Migration analysis was
      performed by the Ein Bild Rontgen Analyse method, with an accuracy of 1 mm. The
      mean total migration after 24 months was 1.13 mm. Using the definition of
      loosening as a total migration of 1 mm, it follows that 30 out of 63 cups (48%)
      were loose at 24 months.

PMID- 10068003
TI  - Low-friction arthroplasty of the hip using alumina ceramic and cross-linked
      polyethylene. A ten-year follow-up report.
AB  - We report the results of our continued review of 14 hip arthroplasties using
      alumina ceramic femoral heads with cross-linked polyethylene cups. There have
      been no complications and a very low rate of penetration. This was 0.02 mm per
      year after an initial 'bedding-in' period of two years. There has been no change
      in the mean rate between our earlier study at six years and the current results
      at 10 to 11 years. The use of these bearing surfaces appears to reduce the
      potential amount of polyethylene debris and may provide the next logical stage in
      the development of the Charnley low-friction arthroplasty.

PMID- 10068004
TI  - Infections associated with dental procedures in total hip arthroplasty.
AB  - Dental procedures may lead to a transient bacteraemia lasting for up to 30
      minutes. Of the numerous cases of total hip arthroplasty (THA) reported which
      have been infected from haematogenous sources, dental procedures have been
      involved only infrequently. We reviewed the records of 2973 patients after THA.
      Of the late infections identified in 52 patients, three (6%) were strongly
      associated with a dental procedure. Infection was diagnosed by culture from the
      affected joint; Streptococcus viridans was identified in two cases and
      Peptostreptococcus in one. One patient had diabetes mellitus and another
      rheumatoid arthritis, both conditions predisposing to infection. The dental
      operations all lasted for more than 45 minutes and no patient received
      perioperative antibiotics. Infection of a THA after dental procedures is more
      common than has been previously suspected. Patients with systemic disease, or who
      are undergoing extensive procedures, should be considered for prophylactic
      antibiotic treatment.

PMID- 10068005
TI  - Long-term results of spherical acetabular osteotomy.
AB  - We have examined the effect of the Wagner spherical acetabular osteotomy on
      preserving the joint in 38 hips with a mean follow-up of 17 years. At the time of
      the initial operation, 55% of patients had clinical symptoms and 30 joints showed
      minimal or absent radiological signs of osteoarthritis. At follow-up, 54% of
      patients had a good functional result. The osteotomy improved the mean centre
      edge angle from -3 degrees to +15 degrees, the mean anterior centre-edge angle to
      23 degrees and the acetabular head index to 75%. The obliquity of the acetabular
      roof decreased from 28 degrees to 16 degrees. One patient improved, but 14
      deteriorated with joint degeneration. Of these, one progressed because of
      postoperative deep-tissue infection and five due to undercorrection. One patient
      needed total joint replacement after 14 years. At 17 years after operation,
      Wagner osteotomy had prevented progression of secondary arthritis in 63% of
      cases.

PMID- 10068006
TI  - Non-operative management of acetabular fractures. The use of dynamic stress
      views.
AB  - To assess the stability of the hip after acetabular fracture, dynamic
      fluoroscopic stress views were taken of 41 acetabular fractures that met the
      criteria for non-operative management. These included roof arcs of 45 degrees, a
      subchondral CT arc of 10 mm, displacement of less than 50% of the posterior wall,
      and congruence on the AP and Judet views of the hip. There were three unstable
      hips which were treated by open reduction and internal fixation. The remaining 38
      fractures were treated non-operatively with early mobilisation and delayed weight
      bearing. At a mean follow-up of 2.7 years, the results were good or excellent in
      91% of the cases. Three fair results were ascribed to the patients' other
      injuries. Dynamic stress views can identify subtle instability in patients who
      would normally be considered for non-operative treatment.

PMID- 10068007
TI  - Fractures of the tibia. Can their outcome be predicted?
AB  - We have carried out a prospective study to determine whether the basic
      descriptive criteria and classifications of diaphyseal fractures of the tibia
      determine prognosis, as is widely believed. A number of systems which are readily
      available were used, with outcome being determined by standard measurements
      including fracture union, the need for secondary surgery and the incidence of
      infection. Many validated functional outcomes were also used. The Tscherne
      classification of closed fractures proved to be slightly more predictive of
      outcome than the others, but our findings indicate that such systems have little
      predictive value.

PMID- 10068008
TI  - Contralateral fracture of the proximal femur. Implications for planning trials.
AB  - In three consecutive years 462 patients over the age of 60 years presented at
      Waikato Hospital, Hamilton, New Zealand, with a fracture of the proximal femur.
      Within two years, 11 (2.4%) returned with a fracture of the contralateral femur.
      If the effectiveness of any form of treatment aiming at reducing the incidence of
      contralateral fracture were subjected to a trial, a sample size of 5000, randomly
      distributed equally between treatment and placebo groups, would be needed for the
      trial to have a power of 80% to detect a reduction.

PMID- 10068009
TI  - Survivorship and radiological analysis of the standard Souter-Strathclyde total
      elbow arthroplasty.
AB  - We undertook a radiological analysis of 186 standard Souter implants to determine
      survivorship and to analyse the pattern of failure in those needing revision. The
      implants had been inserted as a primary procedure in patients with rheumatoid
      arthritis of the elbow at our hospital over the last 12 years. Taking revision as
      an endpoint, the survivorship after 12 years was 87%. If, however, revision and
      loosening, defined as the Hindex value equivalent to demarcation of 1 mm around
      the whole implant, are also included, the survivorship falls to 80%. Of the 24
      implants revised, 18 (75%) were for problems with the humeral component, three
      (12.5%) with the ulnar component and three (12.5%) for instability. Loosening of
      the humeral component occurred when the implant extended into the humerus, with
      the tip moving anteriorly on to the anterior humeral cortex. Our study indicates
      that loosening can be predicted by the rate of change in this angle of extension
      of the prosthesis.

PMID- 10068010
TI  - Patterns of healing of scaphoid fractures. The importance of vascularity.
AB  - We studied 45 patients with 46 fractures of the scaphoid who presented
      sequentially over a period of 21 months. MRI enabled us to relate the pattern of
      the fracture to the blood supply of the scaphoid. Serial MRI studies of the four
      main patterns showed that each followed a constant sequence during healing and
      failure to progress normally predicted nonunion.

PMID- 10068011
TI  - Acute fractures of the scaphoid. Treatment by cast immobilisation with the wrist
      in flexion or extension?
AB  - Acute fractures of the scaphoid were randomly allocated for conservative
      treatment in a Colles'-type plaster cast with the wrist immobilised in either 20
      degrees flexion or 20 degrees extension. The position of the wrist did not
      influence the rate of union of the fracture (89%) but when reviewed after six
      months the wrists which had been immobilised in flexion had a greater restriction
      of extension. We recommend that acute fractures of the scaphoid should be treated
      in a Colles'-type cast with the wrist in slight extension.

PMID- 10068012
TI  - Anterior instability of the glenohumeral joint with humeral avulsion of the
      glenohumeral ligament. A review of 41 cases.
AB  - We studied retrospectively a consecutive series of 547 shoulders in 529 patients
      undergoing operation for instability. In 41, the cause of instability was
      considered to be lateral avulsion of the capsule, including the inferior
      glenohumeral ligament, from the neck of the humerus, the HAGL lesion. In 35, the
      lesion was found at first exploration, whereas in six it was noted at revision of
      a previous failed procedure. In both groups, the patients were older on average
      than those with instability from other causes. Of the primary cases, in 33
      (94.3%) the cause of the first dislocation was a violent injury; six (17.4%) had
      evidence of damage to the rotator cuff and/or the subscapularis. Only four
      (11.4%) had a Bankart lesion. In patients undergoing a primary operation in whom
      the cause of the first dislocation was a violent injury, who did not have a
      Bankart lesion and had no suggestion of multidirectional laxity, the incidence of
      HAGL was 39%.

PMID- 10068013
TI  - Assessment of hindfoot deformity by three-dimensional MRI in infant club foot.
AB  - In 12 infants aged under 16 months with unilateral club foot we used MRI in
      association with multiplanar reconstruction to calculate the volume and principal
      axes of inertia of the bone and cartilaginous structures of the hindfoot. The
      volume of these structures in the club foot is about 20% smaller than that in the
      normal foot. The reduction in volume of the ossification centre of the talus
      (40%) is greater than that of the calcaneus (20%). The long axes of both the
      ossification centre and the cartilaginous anlage of the calcaneus are identical
      in normal and club feet. The long axis of the osseous nucleus of the talus of
      normal and club feet is medially rotated relative to the cartilaginous anlage,
      but the angle is greater in club feet (10 degrees v 14 degrees). The
      cartilaginous structure of the calcaneus is significantly medially rotated in
      club feet (15 degrees) relative to the bimalleolar axis. The cartilaginous anlage
      of the talus is medially rotated in both normal and club feet, but with a smaller
      angle for club feet (28 degrees v 38 degrees). This objective technique of
      measurement of the deformity may be of value preoperatively.

PMID- 10068014
TI  - Unsuccessful surgical treatment of hip dislocation in congenital sensory
      neuropathy with anhidrosis. A case report.
AB  - A six-year-old girl with congenital sensory neuropathy with anhidrosis (CSNA)
      presented with bilateral hip dysplasia and subluxation on the right side.
      Conservative treatment of the hips by closed reduction and a plaster cast was
      unsuccessful. When aged seven years the patient had an intertrochanteric varus
      rotation osteotomy on the right side, but subluxation was again evident after
      five months. A Salter-type pelvic osteotomy was carried out followed by
      immobilisation, but one year later subluxation was present in the right hip and
      dislocation in the left. At the age of nine years, the right femoral head
      resembled a Charcot joint, although walking ability was preserved. In patients
      with CSNA, surgery may not always be advisable.

PMID- 10068015
TI  - Support of the anterior column with allografts in tuberculosis of the spine.
AB  - Fresh-frozen allografts from the humerus were used to help to stabilise the spine
      after anterior decompression for tuberculosis in 47 children with a mean age of
      4.2 years (2 to 9). The average angle of the gibbus, before operation, was 53
      degrees; at follow-up, two years later, it was 15 degrees. Rejection of the graft
      or deep sepsis was not seen. Cross trabeculation between the allograft and the
      vertebral body was observed at six months, with remodelling occurring at
      approximately 30 months.

PMID- 10068016
TI  - Determining the sagittal dimensions of the canal of the cervical spine. The
      reliability of ratios of anatomical measurements.
AB  - The ratio of the sagittal diameter of the cervical canal to the corresponding
      diameter of the vertebral body has been described as a reliable means for
      assessing stenosis of the canal and detecting those at risk of cervical
      neuropraxia. The use of ratio techniques has the advantage of avoiding variation
      in magnification when direct measurements are made from plain radiographs. We
      examined the reliability of this method using plain lateral radiographs of
      unknown magnification and CT scans. We also assessed other possible ratios of
      anatomical measurements as a guide to the diameter of the canal. Our findings
      showed a poor correlation between the true diameter of the canal and the ratio of
      its sagittal diameter to that of the vertebral body. No other more reliable ratio
      was identified. The variability in anatomical morphology means that the use of
      ratios from anatomical measurements within the cervical spine is not reliable in
      determining the true diameter of the cervical canal.

PMID- 10068017
TI  - Ankle arthrodesis using an anterior AO T plate.
AB  - We describe a surgical technique for ankle arthrodesis using an anterior approach
      to the ankle and internal fixation with an anteriorly-placed AO T plate. A total
      of 33 patients who had ankle arthrodeses have been followed retrospectively.
      Thirty-one (94%) of the ankles fused although two patients developed tibial
      stress fractures. Four patients had a superficial infection which did not prevent
      union. The surgical technique is simple, easily reproducible and gives excellent
      clinical results with a high rate of union.

PMID- 10068018
TI  - Mechanical considerations in impaction bone grafting.
AB  - In impaction grafting of contained bone defects after revision joint arthroplasty
      the graft behaves as a friable aggregate and its resistance to complex forces
      depends on grading, normal load and compaction. Bone mills in current use produce
      a distribution of particle sizes more uniform than is desirable for maximising
      resistance to shear stresses. We have performed experiments in vitro using
      morsellised allograft bone from the femoral head which have shown that its
      mechanical properties improve with increasing normal load and with increasing
      shear strains (strain hardening). The mechanical strength also increases with
      increasing compaction energy, and with the addition of bioglass particles to make
      good the deficiency in small and very small fragments. Donor femoral heads may be
      milled while frozen without affecting the profile of the particle size.
      Osteoporotic femoral heads provide a similar grading of sizes, although fewer
      particles are obtained from each specimen. Our findings have implications for
      current practice and for the future development of materials and techniques.

PMID- 10068019
TI  - Transplantation of osteoblast-like cells to the distracted callus in rabbits.
AB  - We carried out limb lengthening in rabbits and then transplanted osteoblast-like
      cells derived from the tibial periosteum to the centres of distracted callus
      immediately after distraction had been terminated. Two weeks later the transaxial
      area ratio at the centre of the distracted callus and the bone mineral density
      (BMD) were significantly higher in the transplanted group, by 21% and 42%,
      respectively, than in the non-injected group or the group injected with
      physiological saline (p < 0.05). Callus BMD as a percentage of density in
      uninvolved bone was also significantly higher in the transplanted group (p <
      0.05) than in the other two groups, by 27% and 20% in the second and fourth
      weeks, respectively (p < 0.05). Mechanically, the callus in the transplanted
      group tended to be stronger as shown by the three-point bending test although the
      difference in fracture strength was not statistically significant. Our results
      show that transplantation of osteoblast-like cells promotes maturity of the
      distracted callus as observed at the second and fourth weeks after lengthening.
      The method appears promising as a means of shortening the consolidation period of
      callus distraction and decreasing complications during limb lengthening with an
      external fixator.

PMID- 10068020
TI  - Cement migration after THR. A comparison of charnley elite and exeter femoral
      stems using RSA.
AB  - Studies using roentgen stereophotogrammetric analysis (RSA) have shown that the
      femoral components of cemented total hip replacements (THR) migrate distally
      relative to the bone, but it is not clear whether this occurs at the cement
      implant or the cement-bone interface or within the cement mantle. Our aim was to
      determine where this migration occurred, since this has important implications
      for the way in which implants function and fail. Using RSA we compared for two
      years the migration of the tip of the stem with that of the cement restrictor for
      two different designs of THR, the Exeter and Charnley Elite. We have assumed that
      if the cement restrictor migrates, then at least part of the cement mantle also
      migrates. Our results have shown that the Exeter migrates distally three times
      faster than the Charnley Elite and at different interfaces. With the Exeter
      migration was at the cement-implant interface whereas with the Charnley Elite
      there was migration at both the cement-bone and the cement-implant interfaces.

PMID- 10068021
TI  - Subsidence of a non-polished stem in revisions of the hip using impaction
      allograft. Evaluation with radiostereometry and dual-energy X-ray absorptiometry.
AB  - We revised 24 consecutive hips with loosening of the femoral stem using impaction
      allograft and a cemented stem with an unpolished proximal surface. Repeated
      radiostereometric examinations for up to two years showed a slow rate of
      subsidence with a mean of 0.32 mm (-2.0 to +0.31). Fifteen cases followed for a
      further year showed the same mean subsidence after three years, indicating
      stabilisation. A tendency to retroversion of the stems was noted between the
      operation and the last follow-up. Retroversion was also recorded when
      displacement of the stem was studied in ten of the patients after two years.
      Repeated determination of bone mineral density showed an initial loss after six
      months, followed by recovery to the postoperative level at two years. Defects in
      the cement mantle and malalignment of the stem were often noted on postoperative
      radiographs, but did not correlate with the degrees of migration or displacement.
      After one year, increasing frequency of trabecular remodelling or resorption of
      the graft was observed in the greater trochanter and distal to the tip of the
      stem. Cortical repair was noted distally and medially (Gruen regions 3, 5 and 6).
      Migration of the stems was the lowest reported to date, which we attribute to the
      improved grafting technique and to the hardness of the graft.

PMID- 10068022
TI  - Determination of Hounsfield value for CT-based design of custom femoral stems.
AB  - Ct and advanced computer-aided design techniques offer the means for designing
      customised femoral stems. Our aim was to determine the Hounsfield (HU) value of
      the bone at the corticocancellous interface, as part of the criteria for the
      design algorithm. We obtained transverse CT images from eight human cadaver
      femora. The proximal femoral canal was rasped until contact with dense cortical
      bone was achieved. The femora were cut into several sections corresponding to the
      slice positions of the CT images. After obtaining a computerised image of the
      anatomical sections using a scanner, the inner cortical contour was outlined and
      transferred to the corresponding CT image. The pixels beneath this contour
      represent the CT density of the bone remaining after surgical rasping. Contours
      were generated automatically at nine HU levels from 300 to 1100 and the mean
      distance between the transferred contour and each of the HU-generated contours
      was computed. The contour generated along the 600-HU pixels was closest to the
      inner cortical contour of the rasped femur and therefore 600 HU seem to be the CT
      density of the corticocancellous interface in the proximal part of cadaver
      femora. Generally, femoral bone with a CT density beyond 600 HU is not removable
      by conventional reamers. Thus, we recommend the 600 HU threshold as one of
      several criteria for the design of custom femoral implants from CT data.

PMID- 10068023
TI  - Hydroxyapatite-coated femoral stems. Histology and histomorphometry around five
      components retrieved at post mortem.
AB  - We performed a histological and histomorphometric examination in five cadaver
      specimens of the femoral and acetabular components and the associated tissue
      which had been recovered between 3.3 and 6.2 years after primary total hip
      arthroplasty (THA) using a proximal hydroxyapatite (HA)-coated titanium alloy
      implant. All had functioned well during the patients' life. All the stems were
      fixed in the femur and showed osseointegration of both the proximal and distal
      parts. The amount of residual HA was greatest in the distal metaphyseal sections,
      indicating that the rate of bone remodelling may be the main factor causing loss
      of HA. The level of activity of the patient was the only clinical factor which
      correlated with loss of coating. The percentage of bone-implant osseointegration
      was almost constant, regardless of the amount of HA residue, periprosthetic bone
      density or the time of implantation. HA debris was seldom observed and if present
      did not cause any adverse or inflammatory reaction. Partial debonding did occur
      in one case as a result of a polyethylene-induced inflammatory reaction.

PMID- 10068024
TI  - Induction of macrophage C-C chemokine expression by titanium alloy and bone
      cement particles.
AB  - Particulate wear debris is associated with periprosthetic inflammation and
      loosening in total joint arthroplasty. We tested the effects of titanium alloy
      (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C
      chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory
      protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed
      and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed
      for expression of macrophage chemokines by immunohistochemistry. Chemokine
      expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles
      in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP
      1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti
      alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in
      macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not
      detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells
      after exposure to particles. Monocyte migration was stimulated by culture medium
      collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to
      MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium
      samples. Release of C-C chemokines by macrophages in response to wear particles
      may contribute to chronic inflammation at the bone-implant interface in total
      joint arthroplasty.

PMID- 10068025
TI  - Cytokine levels in synovial fluid from hips with well-functioning or loose
      prostheses.
AB  - We analysed synovial fluid from 88 hips, 38 with osteoarthritis and 12 with well
      functioning and 38 with loose hip prostheses. The levels of TNF-alpha, IL-1beta
      (71 hips) and IL-6 (45 hips) were measured using the ELISA technique. Joints with
      well-functioning or loose prostheses had significantly increased levels of TNF
      alpha compared with those with osteoarthritis. Hips with aseptic loosening also
      had higher levels of IL-1beta but not of IL-6 compared with those without an
      implant. The levels of TNF-alpha and IL-1beta did not differ between hips with
      stable and loose prostheses. Higher levels of TNF-alpha were found in hips with
      bone resorption of type II and type III (Gustilo-Pasternak) compared with those
      with type-I loosening. The level of cytokines in joint fluid was not influenced
      by the time in situ of the implants or the age, gender or area of the osteolysis
      as measured on conventional radiographs. Our findings support the theory that
      macrophages in the joint capsule increase the production of TNF-alpha at an early
      phase probably because of particle load and in the absence of clinical loosening.
      Since TNF-alpha has an important role in the osteolytic process, the interfaces
      should be protected from penetration of joint fluid.

PMID- 10068026
TI  - The inadequacy of standard radiographs in detecting flaws in the cement mantle.
AB  - Radiological assessment of the cement mantle is used routinely to determine the
      outcome of total hip replacement. We performed a simulated replacement
      arthroplasty on cadaver femora and took standard postoperative radiographs. The
      femora were then sectioned into 7 mm slices starting at the calcar, and high
      resolution faxitron radiographs were taken of these sections. Analysis of the
      faxitron images showed that defects in the cement mantle were observed up to 100
      times more frequently than on the standard films. We therefore encourage the
      search for a better technique in assessing the cement mantle.

PMID- 10068027
TI  - Sensory afferent properties of immobilised or inflamed rat knees during
      continuous passive movement.
AB  - We studied the sensory afferent properties of normal, immobilised and inflamed
      rat knees by recording the activity of the medial articular nerve (MAN). When the
      knee was inflamed by kaolin-carrageenan or immobilised for six weeks, MAN
      activity significantly increased during rest and continuous passive motion (CPM).
      The maximal discharge rate tended to increase depending on the angular velocity
      of the CPM. When the knees were then rested for one hour before again starting
      CPM, activity was further increased at the initial CPM cycle, the 'post-rest
      effect'. Analysis of the conduction velocity showed that 94% and 66% of spike
      units on the recorded discharge of the immobilised and inflamed knees,
      respectively, belonged to fine nerve fibres. Our findings show that the sensory
      receptors in the knee are sensitised in a similar manner by immobilisation and by
      inflammation, suggesting a relationship to pain. The post-rest effect may be
      related to a characteristic symptom of osteoarthritis called 'starting pain'.

PMID- 10068028
TI  - Ankle fractures in diabetics.

PMID- 10068029
TI  - Severe progressive deformities after limb lengthening in type-II fibular
      hemimelia.

PMID- 10068030
TI  - Ultrasonography in developmental hip dysplasia.

PMID- 10068032
TI  - Prognosis in Perthes' disease.

PMID- 10068031
TI  - Wear of polyethylene in artificial hip joints.

PMID- 10068033
TI  - Different methods of treatment related to the bilateral occurrence of Perthes'
      disease.

PMID- 10068034
TI  - Treatment of displaced proximal humeral fractures in elderly patients.

PMID- 10068035
TI  - The conservative management of acute pyogenic iliopsoas abscess in children.

PMID- 10068036
TI  - Contribution of disulphide bonds to antigenicity of Lep d 2, the major allergen
      of the dust mite Lepidoglyphus destructor.
AB  - To study the contribution of the 3 disulphide bonds in the major allergen Lep d 2
      to the antigenic structure, site-directed mutagenesis was performed. Mutants with
      one or more cysteine residues altered were constructed with a histidine residue
      tag for purification purposes and expressed as recombinant proteins in E. coli.
      Seven mutants were analysed: 3 single mutants (Cys 8, Cys 21 and Cys 72), 3
      double mutants (Cys 8-117, Cys 21-16 and Cys 72 77) and one mutant with all 6
      cysteines altered (6 Cys). The evaluation of IgE reactivity in 10 allergic
      patients showed that the disulphide bond formed by cysteine 72 and 77 was the
      single most contributing bond to IgE binding. Mutants with disruption of the Cys
      8-117 bond had a lesser reduction in IgE binding, even though this alteration
      seemed to influence the compact nature of Lep d 2. However, to abolish the IgE
      reactivity almost completely, all 6 cysteines had to be altered. A monoclonal
      antibody previously raised against Lepidoglyphus destructor showed a similar
      binding as human IgE with no reactivity to the Cys 72 77 or the 6 Cys mutant.
      Using skin prick test we found no reaction to the 6 Cys mutant at the
      concentrations tested (1-100 microg/ml) in an Lepidoglyphus destructor allergic
      patient, while the T-cell reactivity was preserved. The 6 Cys mutant of Lep d 2
      may, after further evaluation, be a candidate molecule for improved immunotherapy
      of Lepidoglyphus destructor allergy.

PMID- 10068037
TI  - Evidence for a new transcript of the Epstein-Barr virus/C3d receptor (CR2, CD21)
      which is due to alternative exon usage.
AB  - CR2 extracellular domain is constituted of 15 or 16 Short Consensus Repeats
      (SCR), with additional SCR 11 localized between SCRs 10 and 12. We amplified Raji
      cDNA library, with specific primers where SCR 11 is localized. This generated a
      new fragment of 643 bp (16b SCR), in addition to the two expected transcripts of
      489 (15 SCR) and 667 (16a SCR) bp. Sequencing these three fragments and the
      corresponding genomic DNA, demonstrated the presence of a 24 bp deletion in 16b
      SCR, without change of open reading frame and that this 24 bp region was flanked
      by two splicing acceptor sites. This supported a new alternative splicing of CR2,
      with generation of a third distinct mRNA. This third transcript was expressed in
      human CR2 positive T cells, normal or transformed B cells and EBV negative B cell
      lines. The 24 bp deletion corresponds to a proline-rich region, which may
      influence CR2 conformation and more likely have consequences on CR2 extra and
      intracellular interactions.

PMID- 10068038
TI  - Baculoviral expressed HLA class I heavy chains used to screen a synthetic peptide
      library for allele-specific peptide binding motifs.
AB  - Recombinant baculoviruses encoding truncated HLA-A*0101 and HLA-A*0201 class I
      heavy chains have been isolated and used to infect lepidopteran cells. Proteins
      overexpressed in this system were glycosylated, and consisted of 282 amino acid
      residues after signal sequence cleavage. These class I heavy chains could fold
      into their native conformation in the presence of recombinant human beta2
      microglobulin expressed in Escherichia coli and a synthetic peptide library of
      nonamers bound to resin-support beads. Reconstitution into native ternary
      complexes was detected using a conformation specific monoclonal antibody followed
      by isolation and sequencing of the bound peptides. The motifs obtained for HLA
      A1.1 and HLA-A2.1 peptides are similar although more extensive than those derived
      from sequencing endogenous peptides. This approach selects peptides which form
      very stable complexes regardless of whether these peptides are generated under
      physiological conditions, thereby providing unique supplementary data for
      predicting and designing CTL epitopes. This method is based solely on peptide
      binding to the class I molecule and is therefore independent of any constraints
      imposed by endogenous intracellular processing or transport systems. A comparison
      of the two motifs provides an opportunity to distinguish between the requirements
      of binding from those arising as a function of intracellular processing or
      transport. Our findings are not consistent with a recent report suggesting that
      constraints on the COOH termini of these peptides can be attributed to the
      effects of either intracellular processing or transport. We find that the carboxy
      termini in the class I peptides analyzed to date mimic the endogenous data,
      suggesting that residues in this position contribute to binding affinity.

PMID- 10068039
TI  - Human monoclonal autoantibody fragments from combinatorial antibody libraries
      directed to the U1snRNP associated U1C protein; epitope mapping,
      immunolocalization and V-gene usage.
AB  - To study the localization and function of the U1snRNP associated U1C protein, so
      far only human sera from systemic lupus erythematosus (SLE) overlap syndrome
      patients have been used. Here we report for the first time the isolation of human
      monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and
      semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC
      (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C
      only, and cross-reactive antibodies which also react with U1A and Sm
      B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi
      synthetic libraries and two of the three U1C-specific patient derived
      autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was
      overrepresented. The heavy chain of the two cross-reactive autoantibodies are
      derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are
      targeted by these antibodies. (1) Four U1C specific antibodies recognize an N
      terminal region of U1C in which amino acids 30-63 are essential for recognition,
      (2) two antibodies recognize only the complete U1C protein, and (3) two cross
      reactive and one U1C specific antibody recognize the C-terminal domain in which
      amino acids 98-126 are critical for recognition. The two cross-reactive
      antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein
      (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino
      acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able
      to immunoprecipitate the native U1snRNP particle. The two cross-reactive
      antibodies immunoprecipitate the other Sm containing snRNPs as well. Using
      confocal immunofluorescence microscopy we could show that the major part of the
      U1C protein is localized within the coiled body structure.

PMID- 10068040
TI  - The mouse genome contains two expressed intronless retroposed pseudogenes for the
      sentrin/sumo-1/PIC1 conjugating enzyme Ubc9.
AB  - The ubiquitin conjugating (ubc) E2 enzyme ubc-9 conjugates the ubiquitin-like
      peptide sentrin/SUMO-1/PIC1 to target proteins which include the Fas antigen. We
      show that the mouse genome contains four copies of the ubc-9 gene. These include
      a structural ubc-9 gene consisting of seven exons which encode a protein
      identical to human ubc-9, and three intronless processed pseudogenes. The open
      reading frames (ORF) of two of the pseudogenes, ubc9-psi1 and ubc9-psi2,
      correspond to the cDNA of ubc-9 and encode for proteins which differ from ubc9 by
      three and one amino acid substitutions respectively. The third pseudogene, ubc9
      psi3, contains many mutations and stop codons. ubc9-psi1 and ubc9-psi2 are
      flanked by 5'- and 3'-untranslated (UT) regions homologous to those of the
      structural ubc-9 gene. Both genes contain a polyA tail and direct repeats at both
      ends suggesting that they arose by mRNA retroposition. Both ubc9-psi1 and ubc9
      psi2 are transcribed into mRNA in murine cells. In contrast to ubc9, the protein
      products of ubc9-psil and ubc9-psi2 fail to bind Fas and to complement an yeast
      conditional ubc9 mutant. These results suggest that ubc9-psi1 and ubc9-psi2
      encode for proteins that may interact with targets that differ from those
      recognized by ubc-9.

PMID- 10068042
TI  - Joining the mainstream.

PMID- 10068041
TI  - Conversion of an antibody into an enzyme which cleaves the protein HPr.
AB  - Jel 42 is an IgG which binds to the small bacterial protein, HPr and the
      structure of the complex is known at high resolution. The IgG was expressed as a
      single chain variable fragment (scFv) and the binding to HPr was assessed by
      fluorescence polarization of fluorescein-labelled HPr. The binding constant for
      the IgG was about 20-fold higher than the scFv. Inspection of the structure of
      the complex suggested that it might be possible to convert the scFv into a bond
      specific protease by the introduction of three catalytic residues: a glutamate to
      increase the nucleophilicity of a nearby water molecule, a lysine to increase the
      polarizability of the carbonyl group and a histidine to provide a proton to
      convert the amine into a better leaving group. By trial and error it was found
      that a fourth residue had to be converted into glycine in order to maintain the
      integrity of complimentarity-determining region three of the heavy chain (CDRH3)
      at the binding interface. The resulting quadruple mutant still bound to HPr and
      unlike other mutants, showed weak protease activity as judged from the
      fluorescence polarization assay. The activity was maximum at pH 6 consistent with
      a requirement for a protonated histidine residue. With the aid of HPr fluorescein
      labelled at two different positions, it was demonstrated that the size of the
      products was consistent with cleavage occurring in the vicinity of the target
      peptide bond. The activity was specific for HPr since an excess of bovine serum
      albumin did not interfere with the reaction.

PMID- 10068043
TI  - Peer problems of 9- to 11-year-old children with hemiplegia in mainstream
      schools. Can these be predicted?
AB  - Is it possible to predict relatively early in the life of children with
      disabilities those who are likely to develop peer problems if they get no extra
      help? This question is examined in our prospective study of a representative
      sample of children with hemiplegia attending mainstream schools. Hemiplegia is a
      particularly suitable model for studying integration as it is a relatively
      homogeneous condition that does not usually preclude mainstream placement. Our
      aim was to investigate whether the excess of peer problems could be predicted
      from information obtained some 4 years earlier. A representative sample of 55
      children with hemiplegia in mainstream education was followed prospectively from
      a mean age of 7.1 years (Time 1) to a mean age of 10.7 years (Time 2). Using
      standardized measures of peer rejection, lack of friends, and victimization, two
      thirds of the sample had at least one of these problems at Time 2. A greater
      number of peer problems was primarily predicted by two Time-1 variables: lower IQ
      and more teacher-reported externalizing problems (disruptiveness and
      hyperactivity). A risk index based on these two variables identified a high-risk
      subgroup that might particularly have benefited from early intervention to reduce
      behavioural problems, and nurture social skills. As more children with special
      needs are integrated into mainstream schools, it is increasingly important to
      remember that supporting these children requires appropriate provision to foster
      their social as well as their academic and physical development.

PMID- 10068044
TI  - Prognostic value of flash visual evoked potentials in preterm infants.
AB  - This paper investigates the prognostic value of flash visual evoked potentials
      (VEPs) recorded in preterm infants at birth and at term age with respect to
      severe neurological outcome. Flash VEPs were recorded in 81 preterm infants at
      birth (i.e. <35 weeks' gestation) and repeated in 56 of these infants at term
      age. The preterm infants were assigned to either a healthy or at-risk subgroup
      based on clinical birth factors. Normal ranges of flash-VEP latencies,
      amplitudes, and number of components present were obtained from the subgroup of
      healthy preterm infants and from 68 term infants tested postnatally. The flash
      VEP results of the entire preterm group were compared with the normal ranges and
      any abnormalities noted. Seven preterm infants in the at-risk group died, six of
      whom had abnormal flash VEPs before term age. Of the five infants from the at
      risk group diagnosed with cerebral palsy (CP), three had abnormal flash VEPs
      before term age. Thus the sensitivity and specificity of the flash VEP with
      respect to survival was 86% and 89% respectively, and with respect to the
      development of CP was 60% and 92%. The abnormal features of the flash VEP
      associated with adverse outcomes comprised a delayed N3 component before term age
      and the absence of a positive component (P2) at term age.

PMID- 10068047
TI  - Prevalence of cerebral palsy in north-east Italy from 1965 to 1989.
AB  - This study examines the prevalence of cerebral palsy (CP) in two north-east
      Italian provinces, Padua and Rovigo (overall population 1030 000). Six-hundred
      and ten children with a diagnosis of CP (330 male, 280 female), born between 1965
      and 1989, were studied. The prevalence of CP progressively increased from the
      1960s to the mid-1980s, and then decreased in the 5-year period, 1985 to 1989.
      These quantitative changes were associated with qualitative ones. For example,
      the number of low-birthweight (LBW) infants progressively increased, similar to
      results of epidemiological studies from other European countries. The clinical
      features of the types of CP in this study (hemiplegia, diplegia, ataxic diplegia,
      quadriplegia, pure ataxia, dyskinesia) generally correspond with those described
      in other studies. However, the prevalence of quadriplegia in this study is
      higher. The prevalence of types of CP related to preterm birth, such as diplegia,
      increased over the years, while those associated with term babies, such as
      dyskinesia, decreased. This study suggests that prenatal factors are associated
      with some types of CP, while in others, such as diplegia, quadriplegia, and
      dyskinesia, the perinatal factors are notable. Perinatal factors were associated
      with LBW children, while prenatal factors were greater for normal-birthweight
      infants. The variation in the prevalence of CP over the years, with two peaks
      corresponding with the introduction of neonatal intensive care units in Padua and
      Rovigo, suggests that changes in neonatal care could influence the levels of CP,
      independent of the original presence of predisposing prenatal factors.

PMID- 10068045
TI  - Placental pathology and neurodevelopment of the infant with intrauterine growth
      restriction.
AB  - The placentas of 68 infants with intrauterine growth restriction (IUGR) were
      examined for evidence of impaired uteroplacental circulation and compared with
      those of 65 appropriately grown infants. Infarcts and/or accelerated villous
      maturation were present in the placentas in 27 (40%) of the infants with IUGR
      compared with seven (11%) of the infants without IUGR (P<0.001). The infants were
      followed-up at 4 and 12 months of age and growth parameters recorded. Medical and
      developmental assessments and neuromotor developmental examinations were also
      performed. The 23 infants in the IUGR group with placentas with evidence of
      impaired uteroplacental circulation were compared with the 31 infants with IUGR
      with normal placentas. There was no difference between the groups in growth,
      cognitive development, or neuromotor abnormality. It was concluded that IUGR is
      strongly associated with placental markers of impaired uteroplacental blood flow
      while it would appear that there is no association between placental pathology
      and growth or neurodevelopment in the first year.

PMID- 10068046
TI  - Characterization and comparison of autistic subgroups: 10 years' experience with
      autistic children.
AB  - To summarize our 10-year experience with autistic children at the Tel Aviv Child
      Development Center, the files of all 55 children with autism treated at our
      center over a 10-year period were retrospectively reviewed. Particular attention
      was addressed to the value of the medical work-up in detecting the etiology of
      autism and to factors differentiating infantile autism (IA) from autistic-like
      behavior (ALB). Twenty-four subjects (44%) had IA and 31 (56%) had ALB. These
      subgroups were compared for demographic, perinatal, familial, neurological, and
      psychological findings, and outcome at discharge. Associated medical conditions
      and the yield of metabolic work-up and neuroimaging and electroencephalography
      studies are discussed. The two subgroups differed only in severity of autistic
      symptoms and cognitive function (P<0.05), but not in demographic or
      neurobiological findings. It was concluded that IA and ALB are similar
      conditions, and autism has a wide continuum of clinical expressions.

PMID- 10068048
TI  - Sleep-disordered breathing in patients with myelomeningocele: the missed
      diagnosis.
AB  - Moderate to severe sleep-disordered breathing (SDB) was identified in 20% (17 of
      83) of children with spina bifida/myelomeningocele (SB/MM) at the Montreal
      Children's Hospital. The prevalence of SDB in patients with SB/MM elsewhere has
      not been determined. To establish current practices for identifying SDB in
      patients with SB/MM, questionnaires were sent to the coordinators of the 212
      spina-bifida clinics in Canada and in the United States. Eighty-six (41%)
      questionnaires were returned, representing data on 13 349 patients. Although 67%
      of the responding centers reported availability of cardiorespiratory sleep
      studies, only 996 (7.5%) patients with SB/MM had been tested and only 418 (3.1%)
      patients had been diagnosed with SDB. Across clinics, the prevalence of SDB was
      directly related to the frequency of testing. Of 380 deaths over the past 10
      years, SDB and sudden unexplained death during sleep were identified as the cause
      of death in 49 (12.8%) and 34 (8.9%) patients, respectively. Moderate to severe
      SDB may not have been identified in a significant number of patients with SB/MM
      because they have not been tested.

PMID- 10068049
TI  - Children presenting with convulsions (including status epilepticus) to a
      paediatric accident and emergency department: an audit of a treatment protocol.
AB  - All children who presented in a convulsion, including convulsive status
      epilepticus, to the accident and emergency department over a 12-month period and
      who required treatment, were reviewed retrospectively to identify the
      effectiveness and safety of a specific treatment protocol. This protocol
      recommends the initial use of one, or if necessary, two doses of rectal or
      intravenous diazepam (0.4 mg/kg) followed by the simultaneous administration of
      phenytoin (18 mg/kg) and rectal paraldehyde (0.4 mL/kg), with instructions for
      maximum doses and timings of administration. Eighty-one evaluable children (52
      male) were audited. The mean age of the study population was 4.1 (range 0.1 to
      14.9) years. Overall, the presenting convulsion was successfully terminated in 76
      children (94%) within the accident and emergency department. In 69 children (85%
      of the entire study population) this was after a single dose of diazepam (rectal
      in 41 and intravenous in 28). In only an additional two children did the
      presenting convulsion stop after a second dose of diazepam. In five of the 10
      children (50%) who received paraldehyde and phenytoin as a combination, the
      convulsion stopped. Nine patients (11%) required admission to the intensive-care
      unit, five because of persisting convulsive activity, and four because of
      respiratory depression. The results of this retrospective audit suggest that the
      current treatment protocol appears to be effective and relatively safe in
      treating acute convulsions, including convulsive status epilepticus. The audit is
      to be repeated prospectively to either confirm or refute these findings before
      recommending any changes to the protocol.

PMID- 10068050
TI  - Mild developmental delay due to ring chromosome 19 mosaicism.
AB  - Children with mild developmental delay without dysmorphic features do not often
      have identifiable underlying aetiological factors. We report on a 5-year-old girl
      with mild developmental delay and dysmorphic features which were previously
      unrecognized. She was found to have supernumerary ring chromosome 19 mosaicism
      which was the likely cause of her clinical problems. Her parents' chromosomes
      were normal. A careful examination for dysmorphic features should be done in all
      children with developmental delay. However, these may not be readily apparent in
      babies and very young children. Chromosomal analysis to identify a genetic cause
      and to offer genetic counselling should be considered in all such children unless
      the clinician is absolutely certain that there are no dysmorphic features.

PMID- 10068051
TI  - Hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem
      responses: a report on the first white patient.
AB  - A white Italian boy, aged 5 years and 8 months, is reported with failure to
      thrive, hypotonia, truncal ataxia, psychomotor retardation, and congenital
      horizontal pendular nystagmus with only waves I and II on auditory brainstem
      responses. Our patient's clinical picture resembles that previously reported in
      10 male Oriental patients. He did not manifest spastic diplegia by the age of 2
      years, as did the subjects reported in the literature, but knee-jerk
      hyperreflexia was evident at the most recent clinical reevaluation. Serial brain
      MRI studies revealed a cystic brain lesion and peritrigonal hyperintensities with
      no brainstem abnormalities. To date, no other child with a similar syndrome has
      been described either in Europe or in America. The clinical features of this
      condition are consistent and characteristic. A definitive diagnosis is achieved
      by demonstrating the absence of all waves following wave I or wave II on auditory
      brainstem responses as early as 3 months of age. Due to the predominance of
      males, the occurrence in siblings, the early age at onset, the non-progressive
      course, and the characteristic auditory brainstem response findings, the syndrome
      may have a genetic origin and be attributable to a dysgenetic brainstem lesion.

PMID- 10068052
TI  - Evaluating research in developmental disabilities: a conceptual framework for
      reviewing treatment outcomes.

PMID- 10068053
TI  - Sleep problems in autism: prevalence, cause, and intervention.

PMID- 10068054
TI  - Decrease in cerebral palsy mortality among children and adolescents in Italy from
      1979 to 1993'.

PMID- 10068055
TI  - 'Factors associated with serious skin reactions in children aged 12 years and
      under taking lamotrigine'.

PMID- 10068056
TI  - Increased sensitivity of IL-6-deficient mice to carbon tetrachloride
      hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera.
AB  - Interleukin-6 (IL-6)-deficient mice were found to be much more sensitive to liver
      injury by carbon tetrachloride (CCl4) than mice with an intact IL-6 system. At
      doses of CCl4 ranging from 2 to 3.5 ml/kg body weight, mean mortality in the IL-6
      gene knockout (IL-6-/-) mice was 71% at 24 hours versus 12% in normal IL-6+/+
      mice. At sublethal doses, there was extensive parenchymal necrosis in the livers
      of IL-6-deficient mice, which was not seen in the control animals. Lipid
      peroxidation induced by CCl4 was up to 10-fold higher in the IL-6-/- mice.
      Injections of a chimeric protein containing IL-6 fused to its soluble receptor
      (IL-6R-IL-6 chimera) induced hepatocyte protection against CCl4 damage in both IL
      6-/- and IL-6+/+ mice. Treatment with IL-6R-IL-6 restored the survival of the IL
      6-/- mice to the level of IL-6+/+ animals. Free IL-6 was not effective in
      reducing CCl4-induced liver toxicity, but was as effective as IL-6R-IL-6 in
      reducing death from metastases in a murine melanoma model. Hence the IL-6R-IL-6
      chimera appears to be particularly effective against chemical hepatotoxic injury.

PMID- 10068057
TI  - Interferons in the management of viral hepatitis.
AB  - Since their discovery in 1957, interferons (IFNs) have been noted to have
      protective effects against human viral infections. The use and safety of IFNs in
      patients with acute or chronic hepatitis B or C infections have evolved over the
      last 20 years. The most studied IFN for the management of viral hepatitis is IFN
      alpha, but others have recently been evaluated through controlled clinical
      trials. IFN treatment is not currently indicated for patients with acute
      hepatitis B, but has proven beneficial in chronic hepatitis B. The success of
      treatment in this group of patients has been measured by the normalization of
      liver enzymes, loss of hepatitis B e antigen and loss of detectable serum DNA of
      hepatitis B. It has been estimated in several clinical trials that as many as 40%
      of treated patients will respond to therapy, as defined above. Although only a
      few and limited studies have evaluated the use of IFNs in acute hepatitis C,
      treatment appears to decrease the likelihood of chronicity, and should be
      considered. In chronic hepatitis C, treatment has been effective in achieving
      sustained viral eradication in up to 20% of patients taking the FDA-approved
      dosage of three million units, three times weekly for 6-12 months. However,
      higher doses, longer duration of treatment or combining IFN with other antiviral
      agents may improve the rate of response. It has become clear during the last two
      decades that IFNs have beneficial effects for patients with viral hepatitis B or
      C. Much more effort is needed to establish the optimal dose and duration of
      therapy. Studies addressing the pharmacokinetics of IFNs in patients with viral
      hepatitis are needed, and methods to improve the bioavailability of these
      products to affected tissues such as the liver may improve efficacy and minimize
      side-effects.

PMID- 10068058
TI  - Signalling by cytokines interacting with the interleukin-2 receptor gamma chain.
AB  - The interleukin-2 (IL-2) receptor gamma chain (gammac) is shared by receptor
      complexes used by IL-2, IL-4, IL-7, IL-9 and IL-15, all of which are cytokines
      involved in lymphocyte development and/or activation. Gammac is physically and
      functionally associated with the JAK3 tyrosine kinase. This molecular pair may be
      considered as the trigger of the signalling cascades, inducing the activation of
      JAK1 upon heterodimerization with a cytokine-specific receptor component. JAK1,
      JAK3 and other tyrosine kinases, the nature of which varies between cytokines,
      phosphorylate the receptor, thereby creating docking sites for signalling
      molecules. Among them, PI 3-kinase and downstream effectors play a central role
      in the signalling processes involved in proliferation and inhibition of apoptosis
      for every gammac-interacting cytokine, although the mechanism of activation may
      vary between cytokines. Other important mediators--STAT transcription factors-
      regulate the expression of specific genes. IL-2, IL-7, IL-9 and IL-15 activate
      STAT3 and STAT5, in contrast to IL-4, which activates STAT6. These cytokines also
      trigger specific pathways, such as the MAP kinase cascade for IL-2 and IL-15, and
      the cascade responsible for immunoglobulin gene V-D-J rearrangement in response
      to IL-7.

PMID- 10068059
TI  - Clinical applications of ex vivo cultured CD34+ cells and myeloid progenitors.
AB  - After extensive preclinical work, hematopoietic cellular therapy has recently
      entered a new era of clinical trials involving ex vivo cultured cells. The
      evolution of hematopoietic cell culture from clonogenic assays to large-scale
      static culture systems and bioreactors, and the identification and production of
      hematopoietic growth factors, have in part made this possible. In addition,
      murine models have demonstrated encouraging results with regard to the
      feasibility of infusing cultured cells, as well as to the potential efficacy.
      Several trials have recently been published utilizing ex vivo generated
      hematopoietic progenitors and myeloid progenitors, and are reviewed here. The
      field of clinical hematopoietic cellular therapy, while still in its infancy, is
      progressing rapidly, and promises to offer improved therapeutic options.

PMID- 10068060
TI  - Human dendritic cells: natural adjuvants in antitumor immunotherapy.
AB  - Although T-cell-defined tumor antigens have recently been identified in several
      tumors, human neoplastic cells are considered to be poorly immunogenic. The
      development of clinical approaches to the immunotherapy of human tumors thus
      requires the identification of effective adjuvants. Dendritic cells (DC) are a
      specialized system of antigen-presenting cells (APC) that could be utilized as
      natural adjuvants to elicit antitumor immune responses. In an attempt to overcome
      the problem of the low frequency of mature DC in peripheral blood, several
      methods have been applied for the ex vivo generation of human DC by culturing
      mobilized CD34+ cells or monocytes with combinations of cytokines. As shown in
      murine models as well as in the human system, after loading with peptides or
      tumor lysates or infection with recombinant viral vectors, DC expressing tumor
      antigens are able to elicit specific antitumor T cells and to mediate tumor
      regression. These initial results suggest that this new approach may lead to
      effective antitumor responses even in heavily pretreated patients bearing
      advanced cancers, but further clinical trials are required to validate the
      efficacy of vaccination with tumor-antigen-loaded DC.

PMID- 10068061
TI  - Mechanisms of cell signaling in immune-mediated inflammation.
AB  - Deposition of immune complexes in tissues is the pathogenic mechanism underlying
      tissue injury in a number of diverse clinical conditions affecting the skin,
      joints, blood vessels and renal glomeruli. Initial approaches to the
      understanding of these conditions have stressed the roles of both the activation
      of the complement system and the accumulation of polymorphonuclear leukocytes as
      the main molecular and cellular mechanisms explaining the sequence of events
      leading to tissue damage. Recent findings on (i) the molecular biology of the
      leukocyte chemoattractants, (ii) the chemical structure and function of receptors
      for the Fc portion of the antibody molecule and (iii) the signaling events
      coupled to the engagement of these receptors have led to an understanding of the
      biochemical events involved in immune-complex injury and have provided a
      promising avenue for the development of therapeutic approaches. This review will
      focus on our current understanding of signal transduction events in the effector
      phase of immune-complex-mediated tissue injury.

PMID- 10068062
TI  - Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis
      and immune recovery.
AB  - The identification of interleukin-7 (IL-7) as a critical cytokine in early B- and
      T-cell development, combined with the discovery that it acts on mature T cells,
      opens new avenues for investigating the thymopoietic machinery and manipulation
      of the immune system. Initially, IL-7 was thought to be a growth factor in the
      context of the B-cell lineage in that it stimulates proliferation of early B-cell
      progenitors. However, it appears that this cytokine has a much broader field of
      activity within the network of signal transduction. Indeed, evidence exists to
      support the pivotal involvement of IL-7 in the gene rearrangement of the T-cell
      receptor repertoire that ultimately leads to thymocyte commitment. The finding
      that IL-7 is an inducer of both cytotoxic T-cell- and lymphocyte-activated killer
      cells is one of the significant recent developments in the field of tumor
      immunology. Lately, it has been demonstrated that administration of IL-7 to mice
      after myeloablative treatment accelerates immune recovery via a unique pathway.
      This review of the literature dealing with IL-7 in the realm of immune function
      shows, inter alia, the value of the cytokine in immunosuppressed animals. The
      collection of findings noted in this paper may be considered the forerunner for
      clinical application of IL-7 in a variety of conditions of hematolymphopoietic
      failure.

PMID- 10068063
TI  - Current research on the late Pliocene and Pleistocene deposits north of Homa
      Mountain, southwestern Kenya.
AB  - The late Pliocene and Pleistocene sediments of the Homa Peninsula in southwestern
      Kenya are richly fossiliferous, preserve Early Stone Age archaeological traces
      and provide one of the few paleoanthropological data sets for the region between
      the branches of the East African Rift Valley. This paper presents preliminary
      results of our ongoing investigation of late Pliocene and Pleistocene deposits at
      the localities of Rawi, Kanam East, Kanam Central and Kanjera. While fossils have
      been collected from the peninsula since 1911, little systematic effort has been
      made to place them into a broader litho-and chronostratigraphic framework. This
      project has conclusively demonstrated that fossils occur in good stratigraphic
      context at all of the study localities and that claims of sediment slumping
      (Boswell, 1935) have been greatly overstated (Behrensmeyer et al., 1995; Plummer
      & Potts, 1989). A provisional chronostratigraphic framework based on magneto- and
      biostratigraphy is presented here. We have revised the Plio-Pleistocene
      stratigraphy of the Rawi and Kanam gullies to include three formations: the Rawi,
      Abundu and Kasibos Formations. Based on magneto- and biostratigraphy, these
      formations are dated between approximately three and one m.y.a. (Gauss Chron
      Jaramillo Subchron) (Cande & Kent, 1995). The Apoko Formation unconformably
      overlies the others and may be middle to late Pleistocene in age. All formations
      contain rich patches of fossils, and Acheulean artifacts have been surface
      collected from the Abundu and Kasibos Formations. Deposition of the fossil- and
      artefact-bearing sediments at Kanjera North began in the early Pleistocene and
      continued into the middle Pleistocene. Deposition at Kanjera South began over one
      million years earlier than previously thought, at approximately 2.2 m.y.a., and
      continued into the Olduvai Subchron (1.770-1.950 m.y.a.; Cande & Kent, 1995).
      Excavations have recovered Oldowan artefacts in association with well-preserved
      fossil fauna near the base of the sequence, the oldest archaeological traces yet
      known from southwestern Kenya.

PMID- 10068064
TI  - Research on late Pliocene Oldowan sites at Kanjera South, Kenya.
AB  - The late Pliocene is notable for the appearance of two new hominid genera as well
      as the first archaeological sites, generally attributed to the Oldowan Industrial
      Complex. However, the behavioral ecology of Oldowan hominids has been little
      explored, particularly at sites older than 2.0 Ma. Moreover, debates on Oldowan
      hominid foraging ecology and behavior have centered on data from only two
      regions, and often from single site levels. Here we describe the preliminary
      results of our investigation of Oldowan occurrences at Kanjera South. These
      occurrences preserve the oldest known traces of hominid activity in southwestern
      Kenya, and unlike most of the Oldowan sites in the 2.0-2.5 Ma time interval,
      artefacts are found in spatial association with a well-preserved fauna. In 1996
      and 1997, this project initiated the first excavation program for Kanjera South.
      Magneto- and biostratigraphy indicate that deposition began approximately 2.2 Ma,
      substantially earlier than previously thought. At Excavation 1, artefacts were
      found in spatial association with a taxonomically diverse faunal assemblage in
      Beds KS-1 and KS-2. Excavation 2 yielded a partial hippopotamus axial skeleton
      with artefacts in KS-3. Cores from both sites were incidentally flaked and
      represent a Mode I lithic technology indistinguishable from the Oldowan.
      Approximately 15% of the artefacts were manufactured from non-local raw
      materials, indicating a flow of resources into the area. Stable isotopic analysis
      of KS-1 and KS-2 pedogenic carbonates suggests that the Excavation 1 assemblages
      formed in a relatively open (>75% C4 grass) habitat. The Excavation 1 and 2
      faunas contain a high proportion of equids relative to Oldowan accumulations from
      Bed I Olduvai Gorge, Tanzania. Beds KS-1 and KS-2 thus preserve traces of Oldowan
      hominid activities in a more open setting than has been previously documented.

PMID- 10068065
TI  - Did knuckle walking evolve twice?
AB  - Although African great apes share a similar quadrupedal locomotor behaviour,
      there are marked differences in hand morphology and size between the species.
      Hence, whilst all three species (two genera) of African ape frequently knuckle
      walk as adults, debate remains as to whether this behaviour is derived from a
      common ancestor or whether it evolved in parallel in chimpanzees and gorillas.
      This exploratory morphometric study of the sub-adult and adult wrist of these two
      genera aims to contribute to this debate. A total of twenty-seven dimensions of
      the lunate, triquetral, hamate and capitate of sub-adult and adult Pan
      troglodytes and Gorilla gorilla were analysed in order to determine whether
      carpal dimensions are generally ontogenetically scaled, and whether differences
      in growth trajectories, or length of growth, and adult morphologies can be
      explained by behavioural differences between the two species. Only 56% of all
      dimensions studied were ontogenetically scaled in sub-adults and some of these
      dimensions exhibit differing adult proportions between the two species. In
      general, the dimensions analysed fell into two categories: Pan and Gorilla either
      follow the same growth trajectories (Pattern A) or the Pan reduced major axis
      (RMA) regressions were significantly transposed above those of Gorilla (Pattern
      B). Additionally, it was found that Gorilla carpals appear to cease growing
      relatively earlier than those of Pan. While a small number of differences,
      notably those of the lunate, can be accounted for by differences in behaviour
      between the species, the majority of differences indicate heterochronic
      modifications of development during evolution, which correspond to kinematic
      differences in knuckle walking between the African great apes. In light of
      morphological, behavioural and ecological data currently available it is
      parsimonious to suggest that knuckle walking has evolved in parallel in the two
      lineages.

PMID- 10068066
TI  - Artificial cranial deformation and fossil Australians revisited.
AB  - Based on cranial characters shared by Homo erectus in Java and Homo sapiens in
      Australia, Australasia is widely considered the strongest case for a regional
      origin of modern humans. However, artificial vault deformation has been suggested
      to be the cause of "archaic" characters such as frontal recession in key fossil
      Australian crania. We use log-log plots of cranial arc versus chord measurements
      and we score nonmetric traits often thought to be associated with artificial
      deformation to make systematic comparisons across groups and deformation types to
      identify universal consequences of artificial deformation. Based on our large
      comparative sample (n = 588) apparatus-deformed crania have flatter frontals and
      occipitals and usually more angulated parietals in the sagittal plane than
      undeformed crania, regardless of deformation type. Fossil Australian samples
      exhibit evidence of both undeformed and deformed individuals. The sample from
      Coobool Creek provides evidence that undeformed individuals had more rounded
      frontals than recent Australians. However, many individuals from Coobool Creek,
      Kow Swamp, and Nacurrie exhibit modification of one or more cranial contours. The
      Kow Swamp individuals in particular plot with deformed crania from all regions.
      In addition, the frequency of hyperostotic traits such as bregmatic eminence,
      metopic and sagittal keels in H. sapiens is influenced by both artificial
      deformation and pathological hypervascularity/hyperostosis. Thus it is unwise to
      use cranial contours and these nonmetric traits to infer genetic relatedness
      between Fossil Australians and Indonesian H. erectus.

PMID- 10068067
TI  - Hip bone trabecular architecture shows uniquely distinctive locomotor behaviour
      in South African australopithecines.
AB  - Cancellous bone retains structural and behavioural properties which are time and
      strain-rate dependent. As the orientation of the trabeculae (trajectories)
      follows the direction of the principal strains imposed by daily loadings,
      habitual postural and locomotor behaviours are responsible for a variety of
      trabecular architectures and site-specific textural arrangements of the pelvic
      cancellous network. With respect to the great ape condition, the human trabecular
      pattern is characterized by a distinctive ilioischial bundle, an undivided
      sacropubic bundle, and a full diagonal crossing (approximately 100 degrees) over
      the acetabulum between the ilioischial and the sacropubic bundles. Advanced
      digital image processing (DIP) of hip bone radiographs has revealed that
      adolescent and adult South African australopithecines retained an incompletely
      developed human-like trabecular pattern associated with gait-related features
      that are unique among the extant primates.

PMID- 10068068
TI  - Sex differences in brain/body relationships of Rhesus monkeys and humans.

PMID- 10068069
TI  - Gibraltar and the Neanderthals 1848-1998.

PMID- 10068070
TI  - Benign and malignant cartilage tumors of bone and joint: their anatomic and
      theoretical basis with an emphasis on radiology, pathology and clinical biology.
      II. Juxtacortical cartilage tumors.
AB  - In part I, we reviewed the varied clinical presentations, pathogenesis,
      histologic findings, radiologic findings, and treatment of intramedullary
      cartilaginous lesions of bone. In this section, we will evaluate our cases and
      consultations of juxtacortical cartilaginous tumors. Radiographic differential
      diagnosis includes the numerous juxtacortical lesions particularly
      osteochondroma, parosteal chondroma, Trevor's disease, trauma (fracture and
      periostitis ossificans), and the low- and high-grade surface osteosarcomas. By
      emphasizing pathogenesis in conjunction with radiographic and histologic
      findings, pitfalls in diagnosis and subsequent treatment can be avoided in such
      cases.

PMID- 10068071
TI  - Ultrasound of the plantar aponeurosis (fascia).
AB  - OBJECTIVE: To assess the plantar aponeurosis origin (plantar fascia) using high
      resolution ultrasound. DESIGN: The sonographic appearance of the plantar fascia
      in asymptomatic volunteers was compared with the appearance in: (1) clinical
      idiopathic plantar fasciitis, (2) inflammatory arthropathy without clinically
      active plantar fasciitis and (3) Achilles tendon or ankle ligament injury.
      Patients. There were 48 asymptomatic volunteers (96 heels), 190 patients with
      idiopathic plantar fasciitis (297 heels), 35 with rheumatoid factor negative
      spondyloarthropathy (70 heels), 17 with rheumatoid arthritis (34 heels), 62 with
      clinical Achilles tendinitis (93 heels) and 17 with instability secondary to
      previous ankle ligament injury (17 heels). RESULTS: Compared with the
      asymptomatic volunteers, the symptomatic plantar aponeurosis demonstrated
      significant thickening in patients with clinically unilateral (P<0.001) and
      bilateral (P<0.001) idiopathic plantar fasciitis as well as in patients with
      spondyloarthropathy (P<0.001). However, the plantar aponeurosis on the
      asymptomatic side in patients with unilateral idiopathic plantar fasciitis
      (P<0.2), rheumatoid arthritis (P<0.2) and ankle injury (P<0.1) demonstrated no
      significant thickening. In patients with idiopathic plantar fasciitis, abnormal
      plantar aponeurosis echogenicity was seen in 78% and subcalcaneal bone spurs in
      24%. Peritendinous edema was present in 5% of all symptomatic heels, subcalcaneal
      bone erosion in 4% and intratendinous calcification in 3% of heels.
      Retrocalcaneal bursitis was present in 7% of patients with idiopathic plantar
      fasciitis, 40% with spondyloarthropathy and 19% with rheumatoid arthritis.
      CONCLUSION: Ultrasound allows confirmation of the clinical diagnosis in plantar
      fasciitis and may provide information as to its etiology.

PMID- 10068072
TI  - Radiological assessment of the position of the tibial tuberosity by means of a
      marking wire in knees with patellofemoral arthritis.
AB  - OBJECTIVE: To assess the usefulness of a new axial radiographic technique in
      knees with patellofemoral arthritis (PF-OA). DESIGN AND PATIENTS: After a marking
      wire had been attached to the skin on the tibial tuberosity so that the wire
      matched the width of the patellar tendon, an axial radiograph was taken at 30
      degrees of flexion in 16 normal knees and 14 PF-OA knees in which computed
      tomographic analysis had revealed a laterally positioned tibial tuberosity at 30
      degrees of flexion. The distance of the marking wire from the lateral condyle and
      from the patellar groove was compared between the two groups. RESULTS: The
      marking wire was located significantly laterally in PF-OA knees compared with
      normal knees. CONCLUSION: An axial radiograph with a marking wire on the tibial
      tuberosity is useful for assessing the position of the tibial tuberosity in PF-OA
      knees.

PMID- 10068073
TI  - Spinal osteoblastoma: CT and MR imaging with pathological correlation.
AB  - OBJECTIVES: To illustrate the CT and MRI features of spinal osteoblastomas and
      correlate the imaging with histological findings. DESIGN: In a retrospective
      review the CT and MRI features of spinal osteoblastomas with respect to
      mineralisation, signal intensity (SI), adjacent reactive changes, enhancement
      following gadolinium-DTPA (5 cases) and adjacent soft tissue masses were compared
      and correlated with the histological findings including the degree of osteoid
      formation and matrix mineralisation, vascularity and surrounding reactive changes
      in bone and soft tissue. PATIENTS: Eleven patients (7 males and 4 females; age
      range 8-43 years, mean age 19.5 years) with 12 osteoblastomas (1 patient suffered
      a recurrence) were studied. RESULTS: All lesions showed classical features on CT
      with varying degrees of matrix mineralisation, whereas MRI identified
      mineralisation in only eight of 12 cases. MRI showed low signal intensity of the
      lesion on both T1- and T2-weighted sequences in several cases in the absence of
      heavy mineralisation. In these cases, histological examination revealed diffuse
      osteoid production by the tumour. All patients given gadolinium showed
      enhancement within the tumour on MRI. Reactive bone marrow changes were
      identified on MRI in 10 cases, and in five of these the changes were at multiple
      levels. An adjacent soft tissue mass was demonstrated in five cases, but
      extraosseous tumour was present histologically in only two of these. CONCLUSIONS:
      The MRI appearances of spinal osteoblastomas are varied and show no
      characteristic features. MRI may also overestimate the extent of the lesion due
      to extensive reactive changes and adjacent soft tissue masses. CT should continue
      to be the investigation of choice for the characterisation and local staging of
      suspected spinal osteoblastomas.

PMID- 10068074
TI  - Intracortical osteoblastic osteosarcoma with oncogenic rickets.
AB  - Intracortical osteosarcoma is the rarest variant of osteosarcoma, occurring
      within, and usually confined to, the cortical bone. Oncogenic osteomalacia, or
      rickets, is an unusual clinicopathologic entity in which vitamin D-resistant
      osteomalacia, or rickets, occurs in association with some tumors of soft tissue
      or bone. We present a case of oncogenic rickets associated with intracortical
      osteosarcoma of the tibia in a 9-year-old boy, whose roentgenographic
      abnormalities of rickets disappeared and pertinent laboratory data except for
      serum alkaline phosphatase became normal after surgical resection of the tumor.
      Histologically, the tumor was an osteosarcoma with a prominent osteoblastic
      pattern. An unusual microscopic feature was the presence of matrix mineralization
      showing rounded calcified structures (calcified spherules). Benign osteoblastic
      tumors, such as osteoid osteoma and osteoblastoma, must be considered in the
      differential diagnosis because of the relatively low cellular atypia and mitotic
      activity of this tumor. The infiltrating pattern with destruction or engulfment
      of normal bone is a major clue to the correct diagnosis of intracortical
      osteosarcoma. The co-existing radiographic changes of rickets were due to the
      intracortical osteosarcoma.

PMID- 10068075
TI  - Oncogenic osteomalacia presenting as bilateral stress fractures of the tibia.
AB  - We report on a patient with bilateral stress fractures of the tibia who
      subsequently showed classic biochemical features of oncogenic osteomalacia.
      Conventional radiographs were normal. MR imaging revealed symmetric, bilateral,
      band-like low-signal lesions perpendicular to the medial cortex of the tibiae and
      corresponding to the only lesions subsequently seen on the bone scan. A maxillary
      sinus lesion was subsequently detected and surgically removed resulting in prompt
      alleviation of symptoms and normalization of hypophosphatemia and low 1,25-(OH)2
      vitamin D3. The lesion was pathologically diagnosed as a hemangiopericytoma-like
      tumor. Patients with oncogenic osteomalacia may present with stress fractures
      limited to the tibia, as seen in athletes. The clue to the real diagnosis lies in
      paying close attention to the serum phosphate levels, especially in patients
      suffering generalized symptoms of weakness and not given to unusual physical
      activity.

PMID- 10068076
TI  - Cryptococcoma of the sacrum.
AB  - Cryptococcoma of the sacrum was the initial presentation of systemic
      cryptococcosis in a patient on chronic steroid therapy for autoimmune hepatitis.
      The bone lesion was the only overt manifestation of systemic cryptococcal
      disease, which preceded other clinical manifestations and led to the subsequent
      diagnosis of systemic infection.

PMID- 10068077
TI  - Peroneal nerve palsy caused by intraneural ganglion.
AB  - A case of peroneal nerve palsy caused by an intraneural ganglion is presented.
      The cystic mass was located posterolateral to the lateral femoral condyle and
      extended along the common peroneal nerve distal to the origin of the peroneus
      longus muscle. The nerve was compressed in the narrow fibro-osseous tunnel
      against the fibula neck and the tight origin of the peroneus longus muscle. The
      nerve was decompressed by complete tumor excision and transection of the origin
      of the peroneus longus muscle. Full recovery of nerve function was obtained in 6
      months.

PMID- 10068078
TI  - Deep soft tissue hemangiomas.

PMID- 10068079
TI  - Routinely available indicators of prognosis in breast cancer.
AB  - Diagnosis coupled with prognostication is the challenge for and charge of the
      pathologist. In this time of rapidly developing basic knowledge and increasing
      sophistication in the evaluation of prognostic information, there has also been
      an important re-evaluation of the validity, reliability, and relevance of classic
      histopathology. Also, the precision of and criteria for evaluating tumor size and
      status of regional lymph nodes is under study. Our emphasis in this review is
      tissue pathology and further, its practical relevance to patient management.
      Histopathology remains the basis of diagnosis universally; the addition of other
      elements will increase precision of prediction, particularly of responsiveness to
      individual therapies. Histologic grade may be integrated to substratify high and
      low stage cases into prognostically more useful subsets. Histologic types also
      interact with size and nodal status to predict patients with excellent prognosis.
      Further refinement of these parameters may occur by analysis within clinical,
      pathologic, or therapeutic subsets.

PMID- 10068080
TI  - Prognostic factors for patients with breast cancers 1cm and smaller.
AB  - The widespread use of mammography has resulted in the detection of an increasing
      number of small invasive breast cancers, i.e. those that are 1cm and smaller.
      Patients with these small cancers generally have a low incidence of axillary
      lymph node metastases, and this has led some to question the routine use of
      axillary dissection in these patients. In addition, the prognosis of these
      patients is generally favorable, and the routine use of adjuvant systemic therapy
      is difficult to justify. Nonetheless, some patients with these small invasive
      cancers will have axillary nodal involvement and/or develop metastatic disease.
      The identification of this prognostically unfavorable subset of patients within
      this otherwise favorable group is an important goal of clinical research. In this
      article, we review the available literature on prognostic factors for patients
      with breast cancers 1cm and smaller to help determine which of these features
      might be of value in the identification of patients at risk for axillary lymph
      node involvement and/or metastatic disease.

PMID- 10068081
TI  - Steroid hormone receptors in breast cancer management.
AB  - Estrogen and progesterone receptors (ER and PR) have now been studied in clinical
      breast cancer for more than 20 years. Positive receptor status correlates with
      favorable prognostic features including a lower rate of cell proliferation and
      histologic evidence of tumor differentiation. During the first several years
      after diagnosis, patients with ER-positive tumors tend to have a lower recurrence
      rate; however, this is balanced by a higher recurrence rate in subsequent years
      so that the overall prognostic significance of receptor status is modest. ER and
      PR have their greatest utility in predicting response to hormonal therapy, both
      in the adjuvant setting and for advanced disease. When the assay is done properly
      and cut-offs for ER-negativity and positivity are defined by clinical studies of
      patients treated with endocrine therapy, receptor status is very helpful in
      identifying groups of patients who are very unlikely to benefit from hormonal
      therapy. Tumors that express both ER and PR have the greatest benefit from
      hormonal therapy, but those containing only ER or only PR still have significant
      responses. Two types of estrogen receptors, ERalpha and ERbeta, have now been
      identified. Although there is considerable homology between these receptor forms,
      they appear to have important structural and functional differences that may be
      important for tissue and promoter-specific regulation of gene expression. These
      receptor forms, as well as ER variants and mutants, may also contribute to
      hormonal sensitivity and resistance. PR also exists in two forms, PRA and PRB.
      PRA appears to have repressor functions on both PRB and ERalpha, and the ratio of
      PRA to PRB in clinical breast tumors needs to be studied for its possible
      clinical relevance. Expression of receptor-interacting proteins can also modulate
      ER transcriptional activity, and these too need additional study to determine if
      they are markers of hormonal sensitivity or resistance. In summary, ER and PR
      status are important biomarkers that help physicians individualize therapy.

PMID- 10068082
TI  - S-phase fraction combined with other patient and tumor characteristics for the
      prognosis of node-negative, estrogen-receptor-positive breast cancer.
AB  - Women with estrogen-receptor (ER)-positive breast cancer and no axillary lymph
      node involvement are considered to have excellent overall prognosis. However,
      this population is not homogeneous with regard to risk of recurrence; in fact,
      some of these patients have a prognosis no better than that of many women with ER
      negative tumors or positive axillary nodes. Consequently, better tumor markers
      and better use of those currently available are needed to distinguish patients
      who would benefit from more aggressive therapy from those for whom such therapy
      is unnecessary. A well-defined cohort of over 4000 breast cancer patients from
      National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-14 who had
      ER-positive tumors and no axillary lymph-node involvement was analyzed to
      ascertain the usefulness of tumor cell S-phase fraction for prognosis. The
      significance of clinical tumor size, patient age at surgery, ER and progesterone
      receptor (PgR) expression, and nuclear grade was also explored. Statistical
      methods based on smoothing splines were used to relate treatment failure and
      mortality rates to patient and tumor characteristics. Models for 5- and 10-year
      disease-free survival (DFS) and overall survival were developed and summarized.
      The attenuation of the prognostic importance of covariates over time was
      investigated. After other characteristics were accounted for, a strong
      association was found between S-phase fraction and DFS, as well as survival.
      Tumor size, patient age at surgery, and PgR status were also significantly
      associated with outcome. The diversity of risk in the B-14 population was more
      extreme than is generally recognized. The prognostic capabilities of S-phase,
      tumor size, and PgR status were sharply attenuated as the time from surgery
      increased.

PMID- 10068083
TI  - S-phase fraction and breast cancer--a decade of experience.
AB  - During the past decade, more than 300 articles, abstracts, and book chapters have
      been published about S-phase fraction (SPF) determined by DNA flow cytometry and
      its clinical utility for patients with breast cancer. However, the use of SPF for
      making treatment decisions for breast cancer patients remains controversial.
      After reviewing 273 published articles, we conclude: 1) Despite different
      techniques and cutpoints, correlations between SPF and other prognostic markers
      are relatively consistent across studies; higher SPF is generally associated with
      worse tumor grade, absence of steroid receptors, larger tumors, and positive
      axillary lymph nodes. 2) Higher SPF is generally associated with worse disease
      free and overall survival in both univariate and multivariate analyses; SPF
      values from laboratories that have conducted validation studies can be used, in
      combination with other factors, to estimate the prognosis of patients with
      primary breast cancer. 3) There is considerable variability among laboratories
      regarding assay methodology, cell-cycle analysis techniques, and cutpoints for
      classifying and interpreting SPF; use of SPF values from different laboratories
      is problematic, and there remains a need for standardization of these processes
      and well-designed confirmation studies. We conclude that measurement of SPF does
      have clinical utility for patients with breast cancer, but standardization and
      quality control must be improved before it can be routinely used in community
      settings.

PMID- 10068084
TI  - Prognostic and predictive value of thymidine labelling index in breast cancer.
AB  - In the last few decades, much effort has been directed towards identifying the
      phenotypic or functional aspect of tumor cells which can contribute to a
      biofunctional staging for improving the accuracy of pathologic staging used for
      identifying patients at different risk. Among known biologic factors, the
      proliferative capacity of the tumor cell population, a feature common to all
      tumors, has been widely investigated. Several approaches have been used to
      measure different aspects of the cell cycle. Among these, the thymidine labeling
      index (TLI) represents the fraction of cells in S-phase cell fraction and is
      based on the active incorporation of labelled thymidine into DNA. From basic
      studies conducted on several thousands of patients, the TLI of primary breast
      cancers appears closely related to steroid receptor status and generally
      unrelated to pathologic stage. Retrospective analyses performed on large series
      of patients treated with local regional therapy alone have consistently shown the
      relevance of TLI value to clinical aggressiveness in terms of relapse-free
      survival and overall survival. Moreover, TLI is a prognostic indicator which is
      independent of tumor size, steroid receptors, and p53 and bc12 protein
      expression, and which, together with patient age and tumor size, is able to
      identify patients at different risk of loco-regional or distant metastases.
      Recently, a direct relationship between TLI and response to polychemotherapy has
      been shown in patients with operable and advanced breast cancers. This finding,
      derived from retrospective and recently confirmed in prospective clinical
      studies, has led to the activation of cell kinetics based therapeutic protocols
      for patients with node-negative and one to three node-positive operable breast
      cancers.

PMID- 10068085
TI  - The perikaryal surface of spinal ganglion neurons: differences between domains in
      contact with satellite cells and in contact with the extracellular matrix.
AB  - The perikaryal surface of spinal ganglion neurons undergoes dynamic changes
      throughout life. In particular, numerous slender projections develop and retract
      continuously from this surface. We showed previously that the outgrowth of these
      projections, while an intrinsic property of spinal ganglion neurons, is also
      influenced by the surrounding microenvironment. Since the latter consists of
      satellite cells and the extracellular matrix, we sought to determine the relative
      contributions of each of these components to the outgrowth of perikaryal
      projections. To this end, we took advantage of a little known characteristic of
      the satellite cell sheaths: in the rabbit, these sheaths can exhibit gaps that
      leave the nerve cell body surface directly exposed to the extracellular matrix.
      We compared the surface domains covered by satellite cells with those in direct
      contact with the extracellular matrix. We found that the perikaryal projections
      are abundant in the former domains but are absent in the latter. We also found
      that the perineuronal extracellular matrix of rabbit spinal ganglia contains
      laminin and fibronectin, two glycoproteins that have been reported to promote the
      growth of axonal processes from sensory ganglion neurons. Laminin and fibronectin
      were also present at the level of the gaps in the satellite cell sheath. These
      results: (1) provide additional evidence that environmental factors influence the
      outgrowth of perikaryal projections from spinal ganglion neurons; (2) suggest
      that satellite cells permit the outgrowth of these projections; (3) suggest that
      in the spinal ganglia of adult rabbits the perineuronal extracellular matrix is
      not in itself able to promote the outgrowth of these projections. This study
      provides a further example of the influence that supporting neuroglial cells have
      on sensory ganglion neurons.

PMID- 10068086
TI  - Endothelin and endothelin receptors A and B in the human testis.
AB  - Human testicular capillaries interconnect Leydig cells and seminiferous tubules.
      Microcirculation and blood flow are therefore essential for the maintenance of
      spermatogenesis. The expression and the localisation of ET (endothelin) and its
      receptors in testicular tissue, in seminiferous tubules and in human testicular
      capillaries were studied. ET-1 mRNA was detected in whole testicular tissue and
      in seminiferous tubules whereas isolated testicular capillaries were negative.
      Big ET-1 (Big endothelin 1) and ET peptides were localised in Leydig and Sertoli
      cells whereas interstitial and intramural capillaries (within the lamina propria)
      remained unstained. ET was also found in mature spermatids. ET-A (endothelin
      receptor A) mRNA was detected in seminiferous tubules and whole testicular tissue
      whereas testicular blood vessels were negative. ET-A immunostaining was displayed
      in Leydig and Sertoli cells and in spermatids. ET-B (endothelin receptor B) mRNA
      was detected in whole testicular tissue, seminiferous tubules and in testicular
      capillaries. ET-B peptide was prominent in Leydig cells, peritubular cells,
      endothelial cells and pericytes of interstitial and intramural capillaries as
      well as in vascular endothelial and smooth muscle cells. From these results we
      conclude that ET produced in Leydig and Sertoli cells can act in a paracrine
      manner via ET-B on the human testicular microvasculature and the peritubular
      cells. The presence of both ET-A and ET-B in Leydig cells and of ET-A in Sertoli
      cells leads to the assumption that ET could influence these cells as an autocrine
      factor.

PMID- 10068087
TI  - A developmental study using three antibodies (VOBM1, VOBM2, and VOM2):
      immunocytochemical and electron microscopical analysis of the luminal surface of
      the rat vomeronasal sensory epithelium.
AB  - The development of the rat vomeronasal organ was studied morphologically and
      immunocytochemically, using the monoclonal antibodies (MAbs) VOBM1, VOBM2 and
      VOM2 that react with the luminal surface of the vomeronasal sensory epithelium.
      Postnatal day (P) 7, 14, 21, 28, 35 and adult animals were examined. The
      vomeronasal organ and the blood vessel of the organ markedly increased in size
      and the vomeronasal glands increased in number between P7 and P14. At P35, the
      shape of the vomeronasal organ was similar to that of the adult but its size was
      slightly smaller. Electron microscopy showed that only a few scattered microvilli
      were present on supporting cells, and receptor cells were immature at P7. At P21,
      well-branched microvilli of the receptor cells and many microvilli of the
      supporting cells were observed on the luminal surface of the sensory epithelium.
      At P35, most apical endings of supporting cells and receptor cells were covered
      with numerous microvilli. Less developed areas were also present at the luminal
      surface of the epithelium at P35. At P7, immunoreactivities of the three
      antibodies were observed as discontinuous thin-layered bands only on the luminal
      surface of the sensory epithelium and no immunoreactivity was observed in other
      regions of the vomeronasal organ. Immunoreactivities of the VOBM1, VOBM2 and VOM2
      increased with age and were observed as continuous thin-layered bands on the
      luminal surface of the epithelium by P35. These finding suggest that the
      development of the vomeronasal organ continues after birth and that the organ may
      reach maturity just before puberty (P42-49).

PMID- 10068088
TI  - Intermediate filament proteins in developing human arteries.
AB  - The distribution of intermediate filament proteins in adult human blood vessels
      and in human fetal elastic arteries is relatively well-known. However, the
      distribution of these proteins in the course from neonate to adult has not been
      established. In this investigation, human postnatal arteries were studied with
      immunohistochemistry, using antibodies targeted on the intermediate filament
      proteins desmin, vimentin and cytokeratins 8, 18 and 19. Vimentin was present in
      most smooth muscle cells in all vessels and at all ages. The proportions of
      desmin-expressing cells increased in the elastic arteries during the first year
      of life and was higher in the pulmonary trunk than in the aorta. In the muscular
      arteries, the proportion of desmin-labelled cells increased in the coronary and
      the deep femoral arteries, but remained constant in the renal and the cerebral
      arteries. Cytokeratins were detected in the pulmonary trunk earlier than in the
      aorta. Cytokeratins were present throughout the wall of the ductus arteriosus,
      but desmin was present only in some cells. Thus, there are postnatal changes in
      the distribution of intermediate filament proteins in the elastic arteries and in
      some muscular arteries, whereas the intermediate filament pattern remains
      unchanged in other muscular arteries.

PMID- 10068089
TI  - Confocal microscopy of dentinal tubules in human tooth stained with alizarin red.
AB  - The present study was designed to analyze the structures of dentinal tubules by
      confocal microscopy. Undecalcified ground sections of human teeth were stained
      with alizarin red in 0.1% KOH aqueous solution, and examined by confocal
      microscopy. Alizarin red stained dentinal tubules, interglobular dentine,
      granular layer of Tomes, and the surface of dentine. Interglobular dentine was
      seen between the outer and middle layers of coronal dentine. At the outer layer
      of coronal dentine, the dentinal tubules were thin and showed numerous branches.
      At the middle layer of coronal dentine, dentinal tubules displayed two types. The
      type I tubules are the dentinal tubules that do not show any nodular structures
      and the type II tubules are the dentinal tubules that appear bamboo-like with
      many nodules. In the cross section through the type II tubules, the nodules
      appeared as fine circular tubules surrounding the dentinal tubules. The circular
      tubules of nodules adhered to one side of the dentinal tubules. When the
      fluorescence images were compared with the images taken by transmission light
      mode, the fluorescence of dentinal tubules was seen at the inner surface of
      dentinal tubules, and the fluorescence of nodules was seen at interface between
      peritubular and intertubular dentine. Most of the dentinal tubules were of the
      type II tubules in the teeth from older individuals, whereas the type II tubules
      were scarce in the teeth from younger individuals. At the inner layer of coronal
      dentine, the dentinal tubules have no nodules and branches were scarce. The
      dentinal tubules of radicular dentine were different from those of coronal
      dentine. Most of the dentinal tubules were the type I tubules. Numerous fine
      branches were seen at the outer and middle layers of radicular dentine. No
      interglobular dentine was seen in the root except at the cervical part, and the
      granular layer of Tomes was also positive with alizarin red. At the cervical part
      of the root, interglobular dentine was present and the dentinal tubules displayed
      types I and II.

PMID- 10068090
TI  - A non-destructive technique for 3-D microstructural phenotypic characterisation
      of bones in genetically altered mice: preliminary data in growth hormone
      transgenic animals and normal controls.
AB  - A non-destructive, three-dimensional technique for microstructural phenotypic
      characterisation of skeletal elements in genetically altered mice is presented.
      Preliminary data in bovine growth-hormone transgenic animals and control
      littermates are shown. The technique is based on microcomputed tomography
      (microCT) and digital postprocessing and allows for a differential quantitative
      analysis of the cortical and trabecular bone compartments in the axial and
      peripheral skeleton. The distal femora and the first lumbar vertebral bodies of
      six animals were CT scanned in the axial plane with an isotropic resolution of 20
      microm. The periostal surface and the marrow spaces were segmented fully
      automatically, and the trabecular and cortical compartments were separated
      interactively. After 3-D reconstruction, various regions of interest (diaphyseal,
      metaphyseal and epiphyseal) were selected for the analysis. The femora and
      vertebrae of the transgenic animals showed obvious differences in size, shape,
      and trabecular arrangement compared with the control animals. The total bone mass
      was increased by a factor of two to three, but the trabecular bone was increased
      much more (up to 12 times) than the cortical bone. The transgenic animals showed
      an increased ratio of trabecular vs cortical bone (0.90 to 1.27 vs 0.14 to 0.36
      in the femoral diaphysis) and an elevated trabecular bone volume fraction (49% to
      73% vs 18% to 43% in the femoral metaphysis). The mean 3-D cortical thickness was
      similar in the normal and transgenic animals (values between 93 microm and 232
      microm in the dia- and metaphyses), but the minimal cortical thickness was lower
      in the transgenic animals (22 to 31 microm vs 54 microm to 110 microm in the
      diaphysis). The technique presented is suitable for phenotypic characterisation
      of bone structure in genetically altered mice.

PMID- 10068091
TI  - Projections of the mediolateral part of the lateral septum to the hypothalamus,
      revealed by Fos expression and axonal tracing in rats.
AB  - The lateral septum participates in a variety of functions involving the
      hypothalamus. The present study investigated the effect of an electrical
      stimulation of the mediolateral part of the lateral septum on the expression of
      Fos in the hypothalamic nuclei by using immunohistochemical methods in
      anaesthetised and free-moving rats. We analysed in another series of rats the
      direct projections of the lateral septum by axonal anterograde tracing with
      biotinylated dextran-amine. Tracing was used in combination with Fos labelling in
      a third series of animals. Stimulation induced an expression of Fos in neurones
      located in anteroventral and anterodorsal preoptic nuclei, medial preoptic area,
      anterior hypothalamic nucleus, subparaventricular zone, dorsomedial nucleus,
      lateral hypothalamic area and mammillary nucleus. The distribution of Fos
      immunoreactive neurones conforms to the topographic organisation of direct
      projections from the lateral septum, as revealed by axonal tracing. These results
      suggest that the lateral septum activates definite hypothalamic structures by a
      direct link. Some structures displayed substantial Fos labelling whereas they
      received a slight, or no projection, from the lateral septum. This was
      particularly evident in the core of the ventromedial nucleus and in areas known
      to contain tubero-infundibular neurones. This observation suggests that the
      lateral septum may also exert an indirect control, via polysynaptic links, on
      hypothalamic structures including nuclei involved in neuroendocrine mechanisms.

PMID- 10068092
TI  - Distribution of various neurochemicals within the zona incerta: an
      immunocytochemical and histochemical study.
AB  - To gain insight into the cellular organisation of the zona incerta, we have
      examined the chemoarchitectonic properties of this "uncertain zone". The brains
      of Sprague-Dawley rats and common cats were processed for immunocytochemistry or
      NADPH-diaphorase histochemistry using standard methods. For the
      immunocytochemistry, antibodies to y-aminobutyric acid (GABA), glutamic acid
      decarboxylase (GAD), parvalbumin, calbindin, tyrosine hydroxylase, somatostatin,
      serotonin and glutamate were used. Two general patterns of distribution in the
      zona incerta were seen. First, labelled cells were restricted largely to one of
      the cytoarchitectonically defined sectors of the zona incerta. For instance,
      GABA, GAD and parvalbumin-immunoreactive cells were found principally within the
      ventral sector, NADPH-diaphorase and glutamate-immunoreactive cells within the
      dorsal sector and tyrosine hydroxylase- and somatostatin-immunoreactive cells
      within the rostral sector. Second, labelled cells were scattered somewhat across
      all incertal sectors, with no clear region of concentration. This pattern
      included the calbindin- and serotonin-immunoreactive cell groups. These results
      indicate that the zona incerta is made up of many neurochemically distinct cell
      groups, some of which respect the well-defined cytoarchitectonic boundaries of
      the nucleus, whilst others do not. This rich neurochemical diversity in the zona
      incerta suggests that this nucleus may have differential effects on the different
      structures that it projects to.

PMID- 10068093
TI  - Immunodominant B-cell domains of hepatitis C virus envelope proteins E1 and E2
      identified during early and late time points of infection.
AB  - BACKGROUND/AIMS: We characterized immunoreactive B-cell domains of hepatitis C
      virus (HCV) envelope proteins E1 and E2 by a peptide ELISA using sera of patients
      who were infected by the same isolate of HCV (HCV-AD78). METHODS: Fifty-four
      overlapping peptides which corresponded to the sequence of E1 and E2 of isolate
      HCV-AD78 were used to detect specific antibodies. Three groups of HCV-AD78
      related sera were analyzed. Two groups were from sera obtained at early time
      points of infection (months 4-15) from patients who later resolved infection
      (group A), or who later developed chronic disease (group B). Group C sera were
      from later time points of chronic disease. As a control, sera of chronic HCV
      patients who did not have HCV-AD78 infection were also analyzed (group D).
      RESULTS: In group A, 25 of the 54 peptides produced OD405 above the cut-off,
      whereas 17 peptides produced such values in group B. Only 10 and 3 peptides
      yielded such values in groups C and D, respectively. The overall prevalence of
      antibodies against peptides was high in the early phase of infection (means of
      28.7+/-14.8% and 25.9+/-14.5% in groups A and B, respectively). At later time
      points of chronic infection (group C), the overall prevalence was lower (mean
      18.6+/-15.4%). Group D sera produced the lowest overall prevalence (mean 13.2+/
      14.1%). Three peptides, covering aa271-290, aa481-500 and aa551-570, were
      recognized significantly more frequently (p<0.05) by group A sera than group B
      sera. CONCLUSIONS: We conclude that more linear epitopes of the HCV envelope are
      recognized with a high prevalence of antibodies, as was suggested previously.
      However, most B-cell domains of the HCV envelope induce a similarly high antibody
      response in patients who resolve infection or develop chronic disease.

PMID- 10068094
TI  - Soluble tumor necrosis factor receptors in chronic hepatitis C: a correlation
      with histological fibrosis and activity.
AB  - BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF) is a mediator of inflammation
      and cellular immune response. Soluble TNF receptors (sTNFR) sTNF-R55 and sTNF
      R75, which compete with cellular receptors for the binding of TNF, have been
      detected at high levels in infectious diseases including human immunodeficiency
      virus and HBV infection. In order to investigate the activation of the TNF system
      in HCV infection, we have analyzed the balance between TNF and sTNF-R in 60 HCV
      infected subjects according to their clinical, biological, virological and
      histological characteristics. METHODS: Serum TNF, sTNF-R55 and sTNF-R75 levels
      were determined by ELISA before any therapy and were compared to a control group
      of 60 healthy subjects and a group of 34 HBV-infected patients. RESULTS: Mean TNF
      levels were 50.5+/-4.5 pg/ml in HCV patients, and undetectable (<5 pg/ml) in the
      control subjects. sTNF-R55 and sTNF-R75 levels were significantly higher in HCV
      infected patients than in the controls: 2.88+/-0.14 ng/ml vs. 1.30+/-0.05, (p =
      0.0001), and 9.54+/-0.58 ng/ml vs. 4.19+/-016, (p = 0.0001), respectively. sTNF
      R55 and TNF-alpha levels in HCV patients were not significantly different from
      levels in HBV patients. sTNF-R75 levels were slightly lower than in HBV patients
      (9.54+/-0.58 vs. 11.4+/-0.79 ng/ml, p = 0.03). In contrast to other infectious
      diseases, there was no correlation between levels of sTNF-R and TNF. sTNF-R75 but
      not TNF levels were correlated with aminotransferases levels (p = 0.0001 and p =
      0.0015 for aspartate and alanine aminotransferase, respectively), while sTNF-R55
      levels were significantly correlated only with aspartate aminotransferase levels
      (p = 0.003). sTNF-R75 levels were significantly correlated with the Metavir
      activity index (p = 0.01), and sTNF-R55 and sTNF-R75 levels were significantly
      higher in patients with vs. without cirrhosis (3.22+/-0.21 vs. 2.54+/-0.17 ng/ml
      (p<0.02) and 11.6+/-0.86 vs. 7.5+/-0.53 ng/ml (p<0.001), respectively). sTNF-R55,
      sTNF-R75 and TNF levels were not correlated with viral load, genotype or response
      to interferon therapy. CONCLUSIONS: Levels of soluble TNF receptors, and
      particularly sTNF-R75, are significantly correlated with the severity of the
      disease but not with virological parameters such as quantitative viremia and
      genotype. High TNF-R production could thus suggest that HCV-related liver disease
      involves immunological mechanisms, including activation of the TNF system.

PMID- 10068095
TI  - Early prediction of response in interferon monotherapy and in interferon
      ribavirin combination therapy for chronic hepatitis C: HCV RNA at 4 weeks versus
      ALT.
AB  - BACKGROUND/AIMS: There is consensus that interferon for hepatitis C should be
      stopped if alanine aminotransferase (ALT) remains elevated after 12 weeks;
      however, this may lead to unjust treatment withdrawal in around 20% of potential
      sustained responders. No consensus exists for interferon-ribavirin combination
      therapy. The aim of this study was to assess the predictive value of an HCV RNA
      test at 4 weeks in comparison with ALT, both in interferon monotherapy and in
      interferon-ribavirin combination therapy. METHODS: Plasma HCV RNA was tested at 4
      weeks in 149 naive patients undergoing 6 months and 187 undergoing up to 12
      months of interferon monotherapy, and in 40 non-responders treated for 6 months
      with interferon-ribavirin combination therapy. RESULTS: For 6 and up to 12 months
      of interferon monotherapy, the predictive value for non-response was 99% resp.
      97% for a positive HCV RNA at week 4, versus 97% resp. 91% for an elevated ALT at
      week 12. Using a positive HCV RNA at week 4 as a stopping rule would lead to
      missing 5% resp. 12% of potential sustained responders, versus 10% resp. 28% for
      an elevated ALT at week 12. In interferon-ribavirin combination therapy, the
      predictive value for non-response was 100% for week 4 HCV RNA versus 95% for week
      12 ALT, and 0% potential sustained responders were missed by a test for week 4
      HCV RNA versus 20% for week 12 ALT. The overall sensitivity and specificity of a
      week 4 HCV RNA test was significantly better (area under ROC 0.85) as compared to
      testing ALT at week 4 (0.78, p<0.001), week 8 (0.76, p<0.001) or week 12 (0.78,
      p<0.001). CONCLUSION: A positive HCV RNA test (> or =10(3) copies/ ml) at 4 weeks
      is highly predictive for non-response and leads to significantly less
      misidentification of potential sustained responders than ALT at week 4, 8 or 12,
      both in 6 or up to 12 months interferon monotherapy and in 6 months interferon
      ribavirin combination therapy of chronic hepatitis C.

PMID- 10068096
TI  - Long-term serological follow up and cross-challenge studies in rhesus monkeys
      experimentally infected with hepatitis E virus.
AB  - BACKGROUND/AIMS: The aims of this study were to examine the decline of IgG anti
      HEV antibodies over a period of 7 years in rhesus monkeys experimentally infected
      with hepatitis E virus, and to assess the protectivity of these antibodies by
      challenging the monkeys with a heterologous isolate of hepatitis E virus, 5 years
      after the primary inoculation. METHODS: Nine rhesus monkeys (six non-pregnant and
      three pregnant at the time of hepatitis E virus inoculation) were followed
      serologically and biochemically for 7 years post-inoculation. Based on regression
      analysis, estimated time for IgG anti-HEV titers to reach 1:100 or 1:50 was
      calculated. Three of the monkeys inoculated initially with AKL-90 isolate and
      challenged 2 years later with PUN-85 isolate of hepatitis E virus were
      rechallenged with KOL-91 isolate of the virus, 5 years post-primary inoculation.
      Evidence of viral replication was assessed by measuring serum alanine
      aminotransferase levels, excretion of the virus in feces or bile (reverse
      transcription polymerase chain reaction) and rise in IgG anti-HEV titers (ELISA).
      RESULTS: None of the challenged monkeys showed evidence of disease. In contrast
      to extensive replication of the virus in anti-HEV-negative control monkeys,
      limited replication was noted in one of the challenged monkeys. The estimated
      time for the titers to reach 1:100 or 1:50 varied from 3.15 to 44.9 years (19.4+/
      11.6 years) and 6.9 to 84.3 years (35.4+/-21.3 years), respectively. Decline in
      titers was independent of the pregnancy status at the time of infection or
      reexposure of the monkeys to HEV CONCLUSION: The results show persistence of IgG
      anti-HEV antibodies for a long time and protectivity of low titered antibodies
      against reinfection, leading to disease even after intravenous exposure to a
      heterologous isolate of hepatitis E virus.

PMID- 10068097
TI  - Infection with an unenveloped DNA virus (TTV) in patients with acute or chronic
      liver disease of unknown etiology and in those positive for hepatitis C virus
      RNA.
AB  - BACKGROUND/AIMS: An unenveloped single-stranded DNA virus (TTV) has been reported
      in association with elevated transaminase levels in patients with posttransfusion
      hepatitis and in those with acute or chronic liver disease of unknown etiology.
      To further evaluate the association of TTV with liver disease, TTV DNA was
      searched for in patients with acute or chronic liver disease of various
      etiologies. METHODS: TTV DNA was determined by polymerase chain reaction with
      hemi-nested primers in 64 patients with acute or chronic liver disease of unknown
      etiology and in 100 with acute or chronic liver disease positive for antibody to
      hepatitis C virus (HCV) as well as HCV RNA. RESULTS: TTV DNA was detected in two
      of the seven (29%) patients with acute hepatitis of unknown etiology, but in none
      of the four patients with acute HCV-associated hepatitis. It was detected in 27
      of the 57 (47%) patients with chronic liver disease of unknown etiology at a
      frequency significantly higher (p<0.001) than that in 17 of the 96 (18%) patients
      with chronic HCV-associated liver disease. By contrast, RNA of hepatitis G virus
      was detected in none of the patients with acute hepatitis, and only in one of the
      57 (2%) patients with chronic liver disease of unknown etiology as well as in six
      of the 96 (6%) patients with chronic HCV-associated liver disease. CONCLUSIONS:
      Based on the obtained results, TTV has a role in the development of acute and
      chronic liver disease of unknown etiology.

PMID- 10068098
TI  - Effects of exogenous superoxide anion and nitric oxide on the scavenging function
      and electron microscopic appearance of the sinusoidal endothelium in the
      isolated, perfused rat liver.
AB  - BACKGROUND/AIMS: Functional and morphological alterations of the hepatic
      sinusoidal endothelial cell occur in several models of experimental liver injury
      and in clinical settings. The causes of these alterations are multiple. The aim
      of this study was to test the hypothesis that the early functional impairment and
      morphological alterations of the sinusoidal endothelial cell and hepatic sinusoid
      associated with liver injury are mediated by free radical species, such as
      superoxide anion and nitric oxide. METHODS: Isolated rat livers were perfused by
      recirculation with hemoglobin-free, Krebs-Henseleit bicarbonate buffer and
      presented with a source of superoxide anion (xanthine oxidase+hypoxanthine) or
      nitric oxide (S-nitroso-N-acetyl penicillamine). Hyaluronan uptake (an index of
      sinusoidal endothelial cell scavenging function), thiobarbituric acid-reactive
      substances content of the tissue (a marker of lipid peroxidation), reduced and
      oxidized glutathione (a marker of the thiol system oxidation/reduction state),
      lactate dehydrogenase and alanine aminotransferase activities (markers of
      cytolysis), as well as scanning and transmission electron microscopic appearance
      of the sinusoid were evaluated. RESULTS: At the high concentrations used, both
      free radical generating systems suppressed hyaluronan uptake, increased
      malondialdehyde content of the tissue, enhanced the release of both liver
      enzymes, decreased the total glutathione content of the liver, and altered the
      ratio of reduced/oxidized glutathione. Both free radical species induced dose
      dependent morphological alterations of the sinusoid, consisting of the appearance
      of large gaps replacing the sieve-plated fenestration. CONCLUSIONS: The free
      radical species-induced functional impairment and morphological alterations of
      the liver sinusoid, presented in this study, closely resemble the early in vivo
      changes associated with liver injury under a variety of conditions, such as
      preservation and reperfusion, or administration of hepatotoxicants such as D
      galactosamine, Gram-negative bacterial lipopolysaccharides, acetaminophen,
      alcohol and others. Therefore, we suggest that early liver sinusoid injury,
      observed under these conditions, can be attributed to the action of free
      radicals, such as superoxide anion and nitric oxide.

PMID- 10068099
TI  - Short-term cyclosporine induces a remission of autoimmune hepatitis in children.
AB  - BACKGROUND/AIMS: The current immunosuppressive treatment of patients with
      autoimmune hepatitis consists of prednisone and azathioprine. High doses of
      prednisone used to obtain the remission of the disease are associated with
      serious adverse effects. To avoid harmful consequences of prednisone therapy, we
      proposed to treat patients with oral cyclosporine to obtain the remission of the
      inflammatory process. METHODS: This is a pilot, multinational, multicenter,
      clinical trial involving children with autoimmune hepatitis. Thirty-two children
      were recruited, who according to international criteria were considered as having
      definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months,
      followed by combined low doses of prednisone and azathioprine for 1 month, after
      which cyclosporine was discontinued. Biochemical remission of the disease was
      established by the follow-up of serum transaminase activity levels. Growth
      parameters and adverse effects of the treatment were recorded. RESULTS: Two
      patients were withdrawn from the study: one for non-compliance and the other for
      liver failure which did not improve with cyclosporine. Of the 30 remaining
      patients, 25 normalized alanine aminotransferase activity levels by 6 months and
      all the patients by 1 year of treatment. Z-scores for height showed a trend
      towards improvement during treatment. Adverse effects of cyclosporine were mild
      and disappeared during weaning off the medication. CONCLUSIONS: Cyclosporine
      induced the biochemical remission of the hepatic inflammatory/necrotic process in
      children with autoimmune hepatitis, with few and well-tolerated adverse effects.

PMID- 10068100
TI  - Long-term outcome of asymptomatic liver hydatidosis.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the outcome of
      asymptomatic liver hydatid cysts in a cohort of 33 out of 59 carriers by
      evaluating clinical and ultrasonographic (US) changes 10-12 years after initial
      diagnosis. METHODS: We compared US features and cyst size with the original
      descriptions from 1984-1986. Patients were questioned about hydatid-related
      symptoms and signs. RESULTS: Thirty-three of the 59 carriers could be
      reevaluated, five (15.2%) of whom had undergone surgery without presenting
      symptoms, while of 28 unoperated cases, 21 (75%) remained asymptomatic. Of the
      unoperated cases evaluated by US, in 8/14 (57.1%) there were no modifications in
      cyst size during the 10-12-year period, in five (35.7%) growth was slight (<3 cm)
      and in one (7.1%) the cyst grew 4 cm. Mean cyst growth in all 14 cases was 0.7
      cm. CONCLUSIONS: Despite the limited number of cases, our results show that most
      asymptomatic liver hydatid cases (75%) remain symptom-free for more than 10
      years, regardless of cyst size or type. We believe that such carriers are at low
      risk of developing complications, so that it is difficult to establish specific
      rules for their therapy, if any. Longitudinal follow-up of larger series of
      asymptomatic hepatic hydatidosis cases is essential to gain a deeper insight into
      the natural history of such patients, and to draw up comprehensive guidelines for
      treatment.

PMID- 10068101
TI  - Tumour necrosis factor-alpha promoter polymorphisms in primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: The incidence of primary biliary cirrhosis (PBC) is increased in
      the close relatives of patients, suggesting that genetic factors play a role in
      disease susceptibility. Decreased in vitro production of tumour necrosis factor
      (TNF)-alpha has been reported in PBC patients, suggesting a potential
      aetiological role for this cytokine. The aim of this study was to examine two
      biallelic polymorphisms in the promoter region of the TNF-alpha gene, which may
      play a role in the control of TNF-alpha secretion, as candidate susceptibility
      loci in PBC. METHODS: The polymorphisms at positions -238 and -308 in the TNF
      alpha promoter region were analysed by polymerase chain reaction in 168 unrelated
      PBC patients and 145 local unrelated, geographically matched normal individuals.
      All PBC subjects were also genotyped for HLA DR8, a previously identified
      susceptibility locus in PBC. RESULTS: The -308 TNF1/TNF1 genotype was seen in a
      similar proportion of PBC patients (66%) and controls (60%). However, this
      genotype was found significantly more frequently in the 95 PBC patients with more
      advanced disease (histological stage III/IV) (77%) than in either controls
      (p<0.01, OR = 2.2 [1.2-4.0]) or the PBC patients with earlier disease (38/73
      (52%), p = 0.001 OR 3.1 [1.6-5.9]). Linkage between TNF -308 and HLA DR8 was not
      seen. No association was found between PBC and the biallelic -238 TNF-alpha
      polymorphism, either in the whole PBC population or the histological Stage III/IV
      subgroup. CONCLUSIONS: Our study provides no evidence for involvement of the TNF
      alpha -308 or -238 promoter polymorphisms in genetic predisposition to PBC.
      However, the significantly increased frequency of the -308 TNF1/TNF1 genotype
      seen in 95 patients with more advanced disease raises the possibility that this
      allele may be linked to disease progression rather than susceptibility. The
      finding of different allele frequencies in PBC patients in different disease
      subgroups emphasises the importance of clinical phenotype/casemix in the design
      of disease association studies.

PMID- 10068102
TI  - Association of tumor necrosis factor polymorphism with primary sclerosing
      cholangitis.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis is associated with the HLA
      haplotypes A1-B8-DRB3*0101-DRB1*0301-DQA1*0501-DQB1*0201 and DRB3*0101-DRB1*1301
      DQA1*0103-DQB1* 0603. However, the interpretation of these genetic associations
      is controversial. One explanation may be that HLA-encoded susceptibility is due
      to other genes carried on these haplotypes such as the HLA class III tumor
      necrosis factor genes. The aim of the study was to investigate tumor necrosis
      factor genetics in a large series of well-defined patients. METHODS: One hundred
      and ten HLA genotyped patients and 126 control subjects were studied by
      polymerase chain reaction genotyping for 3 different tumor necrosis factor gene
      polymorphisms: -308, -238 and an Ncol restriction fragment length polymorphism in
      the lymphotoxin alpha gene. RESULTS: Overall, 58% of patients had the TNF2
      allele, compared with 29% of controls, p(c) = 0.0001. No association was found
      with either of the other tumor necrosis factor polymorphisms examined. TNF2 was
      significantly increased in the presence of B8 and DRB3*0101 only, and was
      independent of DRB1*0301 (p(c)<0.04). The associations with B8 and TNF2 were
      stronger than the associations with any of the HLA class II alleles examined.
      CONCLUSION: HLA-encoded genetic susceptibility to primary sclerosing cholangitis
      may be determined by polymorphism within the HLA class III region, in particular
      with the TNF2 allele.

PMID- 10068103
TI  - The liver carnitine pool reflects alterations in hepatic fatty acid metabolism in
      rats with bile duct ligation before and after biliodigestive anastomosis.
AB  - BACKGROUND/AIMS: Rats with long-term bile duct ligation (BDL rats) have impaired
      hepatic fatty acid metabolism and alterations in carnitine homeostasis. Analysis
      of the carnitine tissue and body fluid pools was used as a tool to study hepatic
      fatty acid metabolism in BDL rats and after reversal of bile duct ligation by
      Roux-en-Y anastomosis for 5 (RY5) or 14 days (RY14) METHODS: Control rats were
      pair-fed to treated rats, and all rats were studied after starvation for 24 h.
      Carnitine was analyzed by a radioenzymatic method and by high performance liquid
      chromatography. RESULTS: Both BDL and RY rats had decreased plasma beta
      hydroxybutyrate concentrations, whereas free fatty acid plasma concentrations
      were not different from control rats. Free carnitine plasma concentrations were
      not different between BDL or RY and control rats, whereas acetylcarnitine
      concentrations were decreased in BDL and RY rats, and showed a positive
      correlation with the plasma beta-hydroxybutyrate concentrations. In comparison to
      control rats, the total hepatic carnitine content was increased in BDL and RY
      rats, both when expressed per g tissue and per total liver. This rise in the
      hepatic carnitine content was due to increases in both free and acylcarnitines,
      including acetylcarnitine. In comparison to control rats, the hepatic
      concentration of beta-hydroxybutyrate was decreased in BDL and RY rats, findings
      compatible with impaired formation of ketone bodies from acetyl-CoA. Urinary
      excretion of total carnitine was not different between treated and control rats.
      CONCLUSIONS: Hepatic metabolism of fatty acids is impaired in BDL rats and does
      not recover during the 14 days after Roux-en-Y anastomosis. The increased hepatic
      carnitine content in BDL and RY rats can best be explained by decreased export of
      carnitine from the hepatocytes. The alterations in the hepatic carnitine pool and
      impaired hepatic fatty acid metabolism in BDL and RY rats are compatible with
      impaired ketogenesis.

PMID- 10068104
TI  - Staphylococcus aureus nasal carriage in 104 cirrhotic and control patients. A
      prospective study.
AB  - BACKGROUND/AIMS: Bacterial infections, specially Staphylococcus aureus (S.
      aureus) septicemia, remain a leading cause of death following liver
      transplantation. It has been demonstrated that nasal carriage of S. aureus is
      associated with invasive infections in patients undergoing hemodialysis and could
      be decreased by use of antibiotic nasal ointment. However, in cirrhotic patients,
      the frequency of nasal carriage is unknown. The aims of this study were to
      determine the prevalence of S. aureus nasal carriage in cirrhotic patients and to
      assess nosocomial contamination. METHODS: One hundred and four patients were
      included in a prospective study, 52 cirrhotic and 52 control (hospitalized
      patients without cirrhosis or disease which might increase the rate of nasal
      carriage of S. aureus). On admission and after a few days of hospitalization,
      nasal specimens from each anterior naris were obtained for culture. S. aureus was
      identified by the gram strain, positive catalase and coagulase reactions;
      antibiotic susceptibility was determined using a disk-diffusion test. RESULTS:
      Both groups were similar with regard to age and sex. The prevalence of nasal
      colonization on hospital admission was 56% in cirrhotic patients and 13% in
      control patients (p = 0.001). After an average of 4 days, 42% of cirrhotics and
      8% of control patients were colonized (p = 0.001), without any nosocomial
      contamination. Three strains out of 29 were oxacillin-resistant in cirrhotic
      patients, and none in controls (p>0.05). There was no statistical difference in
      carriage rate according to sex, age, cause of cirrhosis and Child-Pugh score.
      Previous hospitalization (OR, 6.3; 95% CI, 2.3 to 19.9; p = 0.0006) and cirrhosis
      (OR, 4.4; 95% CI, 1.5 to 13.4; p = 0.0048) were independent predictors of
      colonization. CONCLUSION: Cirrhotic patients had a higher S. aureus nasal
      carriage rate than control subjects. Previous hospitalization and cirrhosis
      diagnosis were correlated to nasal colonization. Further studies are necessary to
      determine if nasal decontamination could reduce S. aureus infections after liver
      transplantation.

PMID- 10068105
TI  - Course of platelet counts in cirrhotic patients after implantation of a
      transjugular intrahepatic portosystemic shunt--a prospective, controlled study.
AB  - BACKGROUND/AIMS: The pathogenesis of thrombocytopenia associated with advanced
      liver disease is still controversial. To study the impact of portal decompression
      on this hematologic complication, we conducted a prospective, controlled study to
      compare the course of platelet counts in patients after implantation of a
      transjugular intrahepatic portosystemic shunt (TIPS) with matched controls
      without shunts. METHODS: Fifty-five TIPS patients and 110 controls matched for
      age, sex, Child-Pugh class, etiology of liver disease and baseline platelet count
      were included, and followed for 1 year. Follow-up visits were scheduled after 1
      month, after 3 months, and at 3-month intervals thereafter. RESULTS:
      Nonparametric Mann-Whitney U-tests revealed significantly higher platelet counts
      for TIPS patients as compared to controls from the 1st through the 12th month
      (p<0.01). During the study period, the median platelet count of TIPS patients
      increased by 19.7%, from 104.0/nl (IR: 68.0) to 124.5/nl (IR: 41.0). In contrast,
      during the same period the median platelet count of controls decreased by 17.1%,
      from 102.5/nl (IR: 66.0) to 85.0/nl (IR: 67.5). In the group of cases with
      baseline platelet counts < or =100/nl, platelet counts had increased by at least
      25% at month 12 in 65% of TIPS patients, but in only 5% of controls (p<0.001).
      However, normalization of platelet counts, i.e. > or =150/nl, was not achieved in
      any case. Neither the portosystemic pressure gradient after TIPS implantation,
      nor the percentage of portosystemic pressure gradient reduction during the
      procedure was predictive of platelet response. CONCLUSIONS: TIPS implantation
      increases platelet counts significantly. However, portal hypertension is clearly
      not the only mechanism contributing to thrombocytopenia in advanced liver
      disease.

PMID- 10068106
TI  - Helicobacter pylori, hyperammonemia and subclinical portosystemic encephalopathy:
      effects of eradication.
AB  - BACKGROUND/AIMS: An involvement of Helicobacter pylori in the development of
      hepatic encephalopathy in cirrhotic patients has been proposed, but data
      confirming such an association are lacking. This prospective study aimed to
      assess whether ammonia levels and indicators of subclinical portosystemic
      encephalopathy were influenced by H. pylori status in a series of 62 cirrhotic
      patients. The effects of H. pylori eradication on such parameters were also
      investigated. METHODS: Fasting blood ammonia levels, mental state, number
      connection test, flapping tremor, and EEG tracings were recorded at baseline, and
      in H. pylori-positive patients (as diagnosed by rapid urease test and 14C-urea
      breath test) these parameters were reassessed 2 months following eradication
      therapy. RESULTS: In this series of non-advanced cirrhotic patients, the
      prevalence of H. pylori infection was 52%. No significant differences were
      observed between H. pylori+ and H. pylori- cases with respect to fasting venous
      blood ammonia concentration (47+/-24 vs. 43+/-22 micromol/l) or to the remaining
      parameters assessing portosystemic encephalopathy. In addition, H. pylori
      eradication failed to induce any significant variation in either fasting blood
      ammonia levels (from 45+/-23 to 48+/-26 micromol/l) or neurologic disturbances.
      CONCLUSION: These results indicate that H. pylori infection is not a major
      contributing factor to either fasting blood ammonia levels or parameters
      assessing subclinical portosystemic encephalopathy in patients with non-advanced
      liver cirrhosis.

PMID- 10068107
TI  - Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum
      free cultures of human hepatocytes.
AB  - BACKGROUND/AIMS: Serum-free primary cultures of hepatocytes are a useful tool to
      study factors triggering hepatocyte proliferation and regeneration. We have
      developed a chemically defined serum-free system that allows human hepatocyte
      proliferation in the presence of epidermal growth factor and hepatocyte growth
      factor. METHODS: DNA synthesis and accumulation were determined by [3H]thymidine
      incorporation and fluorometry, respectively. Western blot analyses and co
      immunoprecipitations were used to investigate the association of proteins
      involved in epidermal growth factor and hepatocyte growth factor activation and
      signaling: epidermal growth factor receptor, hepatocyte growth factor receptor
      (MET), urokinase-type plasminogen activator and its receptor, and a member of the
      signal transducer and activator of transcription family, STAT-3. RESULTS: Primary
      human hepatocytes proliferated under serum-free conditions in a chemically
      defined medium for up to 12 days. Epidermal growth factor-receptor and MET were
      present and functional, decreasing over time. MET, urokinase-type plasminogen
      activator and urokinase-type plasminogen activator receptor co-precipitated to
      varying degrees during the culture period. STAT-3 co-precipitated with epidermal
      growth factor-receptor and MET to varying degrees. CONCLUSIONS: Proliferation of
      human hepatocytes can improve by modification of a chemically defined medium
      originally used for rat hepatocyte cultures. In these long-term cultures of human
      hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate
      growth and differentiation by interacting with their receptors and initiating
      downstream signaling. This involves complex formation of the receptors with other
      plasma membrane components for MET (urokinase-type plasminogen activator in
      context of its receptor) and activation of STAT-3 for both receptors.

PMID- 10068108
TI  - Myofibroblasts are responsible for collagen synthesis in the stroma of human
      hepatocellular carcinoma: an in vivo and in vitro study.
AB  - BACKGROUND/AIMS: Marked changes in extracellular matrix occur in the stroma of
      hepatocellular carcinoma, as compared to normal or cirrhotic liver. The cell
      types responsible for extracellular matrix synthesis within hepatocellular
      carcinoma have not been clearly identified. METHODS: In vivo collagen synthesis
      was studied by in situ hybridization and immunohistochemistry for types I, IV, V
      and VI collagen, together with immunolabeling of alpha-smooth muscle actin, a
      myofibroblast marker, and CD34, an endothelial cell marker. In vitro,
      extracellular matrix deposition by cultured myofibroblasts was studied by
      reticulin staining, immunocytochemistry and RNase protection. RESULTS: All
      collagens studied were expressed in the stroma of the tumor, with a higher level
      of type VI and IV collagens than of type I and V. The majority of the cells
      expressing collagen transcripts in human hepatocellular carcinoma stroma were
      alpha-actin positive and CD 34 negative. In vitro experiments demonstrated that
      the hepatocellular carcinoma cell lines HepG2, HuH7 and Hep3B markedly increased
      extracellular matrix deposition by human liver myofibroblasts. This increase was
      mediated by a soluble mediator present in tumor cell conditioned medium. It was
      not explained by an increase in mRNA levels of extracellular matrix components,
      nor by a decrease in the secretion of matrix-degrading proteinases by
      myofibroblasts. CONCLUSIONS: Myofibroblasts are the main source of collagens in
      the stroma of hepatocellular carcinoma. Our data also indicate that tumoral
      hepatocytes increase extracellular matrix deposition by cultured myofibroblasts,
      probably by post-transcriptional mechanisms. The generation of hepatocellular
      carcinoma stroma by myofibroblasts could thus be under control of tumoral cells.

PMID- 10068109
TI  - Optimal timing of liver transplantation for patients with primary biliary
      cirrhosis: use of prognostic modelling.
AB  - BACKGROUND/AIMS: Liver transplantation remains the only definitive treatment for
      patients with end-stage primary biliary cirrhosis, although the optimal timing of
      the procedure remains uncertain. The aim of the study was to use prognostic
      modelling to determine the optimal timing of transplantation for patients with
      primary biliary cirrhosis. METHODS: A prognostic model for predicting the
      survival of patients after transplantation was generated using the Cox regression
      model with data from 312 patients transplanted for primary biliary cirrhosis at
      the Queen Elizabeth Hospital, Birmingham. The prognosis after transplantation was
      compared to that without transplantation (using a previously published prognostic
      index for non-transplantation) both in these patients and in 98 non-transplanted
      primary biliary cirrhosis patients dying from the liver disease, in order to
      establish at what stage the prognosis with transplantation was better than
      without transplantation. RESULTS: The prognostic index for transplantation
      included the following significant prognostic variables: serum bilirubin, serum
      albumin, age, year of transplantation, and the presence of ascites or treatment
      with diuretics. Comparison of prognosis with and without transplantation showed
      that the predicted gain in survival after transplantation becomes increasingly
      positive when the 6-month survival probability in the absence of transplantation
      falls below 0.85. In the non-transplanted patients this occurs on average about 8
      months before death. CONCLUSIONS: Comparison of the prognosis with and without
      transplantation provides a rational method for determining the optimum timing of
      the procedure which occurs approximately when the predicted 6-month survival
      probability without transplantation falls below 0.85.

PMID- 10068110
TI  - Familial Amyloidotic Polyneuropathy: domino liver transplantation.
AB  - BACKGROUND/AIMS: The primary cause of Familial Amyloidotic Polyneuropathy is a
      variant transthyretin gene on chromosome 18. Progressive polyneuropathy followed
      by fatal cardiac and renal failure commonly manifest during middle age. Within 10
      years after onset of clinical symptoms, affected individuals usually die due to
      malnutrition or heart failure. Currently, liver transplantation is the only
      available therapeutic option. METHODS: We performed liver transplantation in two
      patients with Familial Amyloidotic Polyneuropathy carrying the transthyretin-30
      mutant. Two patients aged more than 50 years received the two explanted
      amyloidotic livers. This procedure is called Domino liver transplantation. We
      report the outcome in the studied subjects and analyze the metabolic consequences
      of this procedure. RESULTS: We determined the serum half-life of transthyretin-30
      as 2.25 days using daily monitoring of transthyretin-30 levels. An affected
      amyloidotic patient had an increased serum concentration of lipoprotein(a) of 78
      mg/dl before transplantation. The tumor patient, who received the organ from this
      affected patient, developed an almost identical serum concentration of
      lipoprotein(a) after liver transplantation, confirming the liver as the primary
      site of synthesis of this lipoprotein. CONCLUSION: Once Domino liver
      transplantation has been performed, the impact of the liver-dependent metabolism
      of specific proteins of interest can be studied.

PMID- 10068111
TI  - Rapid clearance of transplanted hepatocytes from pulmonary capillaries in rats
      indicates a wide safety margin of liver repopulation and the potential of using
      surrogate albumin particles for safety analysis.
AB  - BACKGROUND/AIMS: Applications of liver repopulation by hepatocyte transplantation
      require analysis of cell biodistributions, particularly when portasystemic
      shunting coexists. The aims of this study were to determine the fate of
      hepatocytes transplanted into the pulmonary vascular bed and to examine whether
      cell biodistributions could be approximated by convenient surrogates. METHODS:
      Rat hepatocytes and macroaggregated serum albumin particles of similar sizes were
      injected into the portal and pulmonary vascular beds of rats, followed by
      biodistribution, survival and function analyses. RESULTS: Although functionally
      intact, virtually all hepatocytes were cleared from the pulmonary capillaries
      within 24 h. Serum albumin levels increased minimally in Nagase analbuminemic
      rats with or without portacaval shunting to enhance delivery of portal factors to
      transplanted cells in lungs. Despite intravenous injection of hepatocytes
      approaching >1x10(9) cells in humans, the hemodynamic changes were limited to
      transient increases in right atrial pressures. The hepatocyte distributions in
      specific vascular beds were largely reproduced by macroaggregated human serum
      albumin particles. CONCLUSIONS: Incidental intrapulmonary cell translocations
      during liver repopulation will have a wide safety margin. Use of macroaggregated
      serum albumin particles as surrogates for initial short-term biodistribution and
      safety analysis will advance hepatocyte transplantation, as the cost of GLP
      certified laboratories and consumption of scarce donor livers will be avoided.

PMID- 10068112
TI  - Evaluation of a novel bioartificial liver in rats with complete liver ischemia:
      treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte
      viability.
AB  - BACKGROUND/AIMS: There is an urgent need for an effective bioartificial liver
      system to bridge patients with fulminant hepatic failure to liver transplantation
      or to regeneration of their own liver. Recently, we proposed a bioreactor with a
      novel design for use as a bioartificial liver (BAL). The reactor comprises a
      spirally wound nonwoven polyester fabric in which hepatocytes are cultured (40 x
      10(6) cells/ml) as small aggregates and homogeneously distributed oxygenation
      tubing for decentralized oxygen supply and CO2 removal. The aims of this study
      were to evaluate the treatment efficacy of our original porcine hepatocyte-based
      BAL in rats with fulminant hepatic failure due to liver ischemia (LIS) and to
      monitor the viability of the porcine hepatocytes in the bioreactor during
      treatment. The latter aim is novel and was accomplished by applying a new species
      specific enzyme immunoassay (EIA) for the determination of porcine alpha
      glutathione S-transferase (alpha-GST), a marker for hepatocellular damage.
      METHODS: Three experimental groups were studied: the first control group (LIS
      Control, n = 13) received a glucose infusion only; a second control group (LIS No
      Cell-BAL, n = 8) received BAL treatment without cells; and the treated group (LIS
      Cell-BAL, n = 8) was connected to our BAL which had been seeded with 4.4 x 10(8)
      viable primary porcine hepatocytes. RESULTS/CONCLUSIONS: In contrast to previous
      comparable studies, BAL treatment significantly improved survival time in
      recipients with LIS. In addition, the onset of hepatic encephalopathy was
      significantly delayed and the mean arterial blood pressure significantly
      improved. Significantly lower levels of ammonia and lactate in the LIS Cell-BAL
      group indicated that the porcine hepatocytes in the bioreactor were metabolically
      activity. Low pig alpha-GST levels suggested that our bioreactor was capable of
      maintaining hepatocyte viability during treatment. These results provide a
      rationale for a comparable study in LIS-pigs as a next step towards potential
      clinical application.

PMID- 10068113
TI  - Autoimmune cholangitis in a patient with celiac disease: a case report and review
      of the literature.
AB  - Autoimmune cholangitis is a rare chronic cholestatic liver disease. We describe
      the case of a 65-year-old woman with celiac disease who presented to us with
      fever, jaundice and weight loss. Serum biochemical study showed marked increase
      in alkaline phosphatase and gammaGT levels. Antinuclear antibodies were positive,
      while antimitochondrial and anti-smooth-muscle antibodies were negative. Liver
      biopsy was compatible with primary autoimmune cholangitis. The patient was
      successfully treated with azathioprine and methylprednisolone. We describe here
      the uncommon association of autoimmune cholangitis with celiac disease and review
      the prevalence of liver diseases in patients with celiac disease.

PMID- 10068114
TI  - Premalignant lesions and hepatocellular carcinoma in a non-cirrhotic alcoholic
      patient with iron overload and normal transferrin saturation.
AB  - A 66-year-old white man had a hepatic resection for a 6-cm well-differentiated
      hepatocellular carcinoma which had developed in a non-cirrhotic liver. The only
      risk factors found were heavy drinking, smoking and heterozygosity for the C282Y
      mutation of the HFE gene. The liver was mildly fibrotic and overloaded with iron.
      It also contained numerous iron-free hepatocellular lesions from <1 to 10 mm,
      suggesting a premalignant change. These lesions were of three types: (i) iron
      free foci, (ii) hyperplastic nodules and (iii) dysplastic nodules with severe
      dysplasia or even foci of well-differentiated grade I hepatocellular carcinoma.
      This observation suggests the possibility of malignant transformation of the
      liver in the newly-described syndrome of iron overload and normal transferrin
      saturation. It also illustrates the multistep process of carcinogenesis in the
      non-cirrhotic liver.

PMID- 10068115
TI  - Images in hepatology. Reversible nail changes in primary biliary cirrhosis after
      liver transplantation.

PMID- 10068116
TI  - Genetics of tumour necrosis factor (TNF) in autoimmune liver diseases: red hot or
      red herring?

PMID- 10068117
TI  - Biliary imaging: magnetic resonance cholangiography versus endoscopic retrograde
      cholangiography.

PMID- 10068118
TI  - DNA vaccine strategies for hepatitis C.

PMID- 10068119
TI  - Improvement of sarcoidosis under therapy with interferon-alpha 2b for chronic
      hepatitis B virus infection.

PMID- 10068120
TI  - Retrospective analysis of the impact of HIV infection and alcohol use on chronic
      hepatitis C in a large cohort of drug users.

PMID- 10068121
TI  - Cholinesterase-producing hepatocellular carcinoma.

PMID- 10068122
TI  - Elevated liver enzymes preceding vessel involvement in Takayasu's arteritis.

PMID- 10068123
TI  - Prevalence of antibodies against canine herpesvirus 1 in dogs in The Netherlands
      in 1997-1998.
AB  - Canine herpesvirus (CHV1) is found in dogs all over the world and may spread by
      oronasal or sexual contact. We developed an enzyme-linked immunosorbent assay
      (ELISA) for the detection of antibodies against CHV1 in dogs. The antigen used
      for this ELISA was prepared by purifying CHV1 virions from the medium of infected
      A72 cells. To investigate the prevalence of CHV1 in The Netherlands, a panel of
      145 sera of dogs boarding at a kennel in Lelystad, The Netherlands, was screened
      using this ELISA. The dogs originated from all parts of The Netherlands and
      represented many different breeds. The sera were collected both at the start and
      at the end of the boarding period. Of the 145 paired sera 61 (42.1%) were
      positive, 79 (54.5%) were negative and 5 (3.4%) could not be attributed to either
      group. None of the negative dogs became seropositive during the boarding period,
      which lasted normally two to three weeks. We also tested 79 individual sera taken
      from dogs at various other places in The Netherlands and found that 27 (34.2%)
      were positive. Hence, in total 224 dog sera, collected from April 1997 to March
      1998, were tested and 88 (39.3%) were found positive. We conclude that the
      prevalence of CHV1 seropositive dogs in The Netherlands in this period was about
      40%, and that boarding at a dogs kennel did not contribute to the spread of CHV1.
      In addition, CHV1 has been isolated from two clinical cases of fatal haemorrhagic
      disease in The Netherlands.

PMID- 10068124
TI  - Species-specific B-cell epitope on the C-terminal region of the alpha antigen
      from Mycobacterium intracellulare in mice.
AB  - The alpha antigen, which is an immunodominant antigen, is a 30 kDa protein
      secreted by mycobacterial species. The C-terminal regions of alpha antigens are
      quite divergent. We investigated the question of whether the C-terminal regions
      of Mycobacterium avium alpha antigen (A-alpha), M. intracellulare alpha antigen
      (I-alpha) and M. bovis BCG alpha antigen (B-alpha) contained species-specific B
      cell epitopes. We investigated the reactions of these peptides with anti-A-alpha,
      anti-I-alpha and anti-B-alpha sera prepared from BALB/c in a Western blot assay
      and ELISA. The C-terminal regions of I-alpha reacted exclusively with anti-I
      alpha serum. The results of the inhibition assay of antibodies binding to I-alpha
      by peptides of C-A-alpha, C-I-alpha, and C-B-alpha are that only C-I-alpha
      inhibited the binding of antibodies to C-I-alpha. We found that the C-terminal
      region was B-cell epitope-specific to I-alpha in BALB/c mice.

PMID- 10068125
TI  - Brucella melitensis 16M: characterisation of the galE gene and mouse immunisation
      studies with a galE deficient mutant.
AB  - The galE gene of Streptomyces lividans was used to probe a cosmid library
      harbouring Brucella melitensis 16M DNA and the nucleotide sequence of a 2.5 kb
      ClaI fragment which hybridised was determined. An open reading frame encoding a
      predicted polypeptide with significant homology to UDP-galactose-4-epimerases of
      Brucella arbortus strain 2308 and other bacterial species was identified. DNA
      sequences flanking the B. melitensis galE gene shared no identity with other gal
      genes and, as for B. abortus, were located adjacent to a mazG homologue. A
      plasmid which encoded the B. melitensis galE open reading frame complemented a
      galE mutation in Salmonella typhimurium LB5010, as shown by the restoration of
      smooth lipopolysaccharide (LPS) biosynthesis, sensitivity to phage P22 infection
      and restoration of UDP-galactose-4-epimerase activity. The galE gene on the B.
      melitensis 16M chromosome was disrupted by insertional inactivation and these
      mutants lacked UDP-galactose-4-epimerase activity but no discernible differences
      in LPS structure between parent and the mutants were observed. One B. melitensis
      16M galE mutant, Bm92, was assessed for virulence in CD-1 and BALB/c mice and
      displayed similar kinetics of invasion and persistence in tissues compared with
      the parent bacterial strain. CD-1 mice immunised with B. melitensis 16M galE were
      protected against B. melitensis 16M challenge.

PMID- 10068126
TI  - Protection of just weaned pigs against infection with F18+ Escherichia coli by
      non-immune plasma powder.
AB  - The anti-colonization effect of porcine plasma powder against experimentally
      induced postweaning diarrhoea and oedema disease in just weaned piglets was
      examined. Piglets were infected with an Escherichia coli strain expressing F18ac
      fimbriae and producing SLTIIv- and LT-toxins. Reduced fecal excretion of the
      challenge strain and protection against clinical symptoms was obtained by daily
      supplementation of the feed with either 90 or 45 g of plasma powder. However, the
      piglets receiving 90 g of plasma powder a day showed diarrhoea and reduced weight
      gain compared to the piglets receiving 45 g of plasma powder a day. The diarrhoea
      was attributed to biogenic amines released from excessive protein in the diet.

PMID- 10068127
TI  - Effects of macrophage inhibitory factor-A3 (MIF-A3) on cytokine secretion and
      phagolysosome fusion in murine macrophages.
AB  - Macrophage inhibitory factor-A3 (MIF-A3) is a fraction derived from Mycobacterium
      avium serovar 2 (Mav2) that consists of a small amine containing compound
      (peptide), trehalose and two or three short chain fatty acids. MIF-A3 has been
      shown to inhibit candidacidal activity of murine thioglycolate-elicited
      peritoneal-derived macrophages and bovine peripheral blood monocytes, and
      scavenge reactive oxygen intermediates. In this study, MIF-A3 was evaluated for
      its effect on secretion of IL-1beta, IL-6, IL-10, TNFalpha and GM-CSF in C57BL/6
      murine thioglycolate-elicited peritoneal-derived macrophages, with and without
      pre-incubation with affinity purified goat anti-MIF-A3 IgG, using ELISA cytokine
      kit analysis. Results of this study suggest that anti-MIF-A3 IgG does not enhance
      clearance of Mav2, alter phagocytosis or alter phagosome-lysosome interactions as
      determined by electron microscopy in Mav2 infected macrophages. MIF-A3 does
      induce secretion of IL-6, but does not induce secretion of TNFalpha, IL-1beta,
      and GM-CSF. TNFalpha has been previously shown to reduce growth, while IL-6 has
      been shown to enhance growth of M. avium. Since IL-6 appears to enhance growth of
      M. avium and MIF-A3 induces IL-6 secretion, MIF-A3 may be responsible for
      enhanced intracellular growth in M. avium infections and be a factor in the
      pathogenesis of M. avium infections.

PMID- 10068128
TI  - Development of a typing system for epidemiological studies of porcine toxin
      producing Pasteurella multocida ssp. multocida in Denmark.
AB  - The aim of the present study was to evaluate capsular-typing, plasmid-profiling,
      phage-typing and ribotyping for epidemiological studies of toxin-producing
      Pasteurella multocida ssp. multocida in Denmark. The evaluation of methods was
      based on 68 strains from nasal swabs and 14 strains from pneumonic lungs. Strains
      from lungs were all of capsular Type A, whereas strains from nasal swabs were of
      both capsular Types A and D. Only 9% of the strains contained plasmids, which
      could not be associated with antibiotic resistance. Phage-typing divided 61% of
      strains into 10 groups, while 39% were non-typable. CfoI ribotyping divided
      strains into four groups of which one type contained 94% of isolates. HindIII
      ribotyping divided strains into 18 types. A total of 18 strains from The
      Netherlands, UK and USA were subjected to HindIII ribotyping, resulting in 13
      types of which six were identical to ribotypes of Danish strains. Phage-typing of
      isolates from an outbreak of atrophic rhinitis involving six herds in 1985 showed
      the existence of an epidemic strain. This type was recognised in the herd
      suspected of being the source of the infections and in four of the five infected
      herds. These findings were supported by HindIII ribotyping, as 85% of isolates
      from all herds were assigned to one ribotype. In conclusion, HindIII ribotyping
      seems to represent a useful tool for epidemiological studies of toxigenic P.
      multocida ssp. multocida.

PMID- 10068129
TI  - Genetic heterogeneity of porcine and ruminant pestiviruses mainly isolated in
      Japan.
AB  - The genetic variability of porcine and ruminant pestiviruses was studied by
      comparative nucleotide sequence analysis of 73 isolates (42 porcine and 31
      ruminant), including 65 Japanese isolates (35 porcine and 30 ruminant). The 5'
      untranslated region (UTR) amplified by reverse transcriptase-polymerase chain
      reaction (RT-PCR) was determined by direct sequencing and phylogenetic analysis
      was performed from the nucleotide sequence data. Most porcine isolates were
      divided into two major subgroups, classical swine fever virus (CSFV) subgroup 1
      (CSFV-1, represented by Brecia strain) and subgroup 2 (CSFV-2, represented by
      Alfort strain). However, the Japanese Kanagawa/74, Okinawa/86, Okinawa/86-2 and
      Thai CBR/93 strains were the most distinct variants and these were assigned to
      another new disparate subgroup, CSFV-3 (represented by p97 strain). Most ruminant
      isolates were classified as the bovine viral diarrhoea virus (BVDV) genotype-I
      (BVDV-I) and subdivided into two subgroups, BVDV-Ia (represented by the NADL
      strain) and Ib (represented by the Osloss strain). Two bovine isolates (MS-1 and
      SY-89) and a contaminating strain (V/FLL) from an ovine cell line were classified
      as BVDV genotype-II (BVDV-II) on genetic characteristics. These data suggested
      that the detection and phylogenetic analysis of 5'-UTRs are useful for the rapid
      characterization of field isolates.

PMID- 10068130
TI  - Capillary electrophoresis of subcellular-sized particles.
AB  - Utilization of capillary electrophoresis (CE) for characterization and analytical
      separation of submicron- and micron-sized organic and inorganic particles as well
      as biological vesicles is reviewed. CE has been applied to charged polystyrene
      size standards, inorganic and organic colloidal particles, lipoprotein particles,
      liposomes, microsomes and viruses. These particle separations generally occur in
      a size-dependent manner and provide values of electrophoretic mobility which are
      in good agreement with those obtained by other electrophoretic techniques.

PMID- 10068131
TI  - Oriented immobilization of biologically active proteins as a tool for revealing
      protein interactions and function.
AB  - The advantages of oriented immobilization of biologically active proteins are
      good steric accessibilities of active binding sites and increased stability. This
      not only may help to increase the production of preparative procedures but is
      likely to promote current knowledge about how the living cells or tissues
      operate. Protein inactivation starts with the unfolding of the protein molecule
      by the contact of water with hydrophobic clusters located on the surface of
      protein molecules, which results in ice-like water structure. Reduction of the
      nonpolar surface area by the formation of a suitable biospecifc complex or by use
      of carbohydrate moieties thus may stabilize proteins. This review discusses
      oriented immobilization of antibodies by use of immobilized protein A or G. The
      section about oriented immobilization of proteins by use of their suitable
      antibodies covers immobilization of enzymes utilizing their adsorption on
      suitable immunosorbents prepared using monoclonal or polyclonal antibodies,
      preparation of bioaffinity adsorbent for the isolation of concanavalin A and
      immobilization of antibodies by use of antimouse immunoglobulin G, Fc-specific
      (i.e. specific towards the constant region of the molecule). In the further
      section immobilization of antibodies and enzymes through their carbohydrate
      moieties is described. Oriented immobilization of proteins can be also based on
      the use of boronate affinity gel or immobilized metal ion affinity chromatography
      technique. Biotin-avidin or streptavidin techniques are mostly used methods for
      oriented immobilization. Site-specific attachment of proteins to the surface of
      solid supports can be also achieved by enzyme, e.g., subtilisin, after
      introduction a single cysteine residue by site-directed mutagenesis.

PMID- 10068132
TI  - Use of magnetic techniques for the isolation of cells.
AB  - Magnetic separation is an emerging technology using magnetism, sometimes in
      combination with conventional separation or identification methods, to purify
      cells, cell organelles and biologically active compounds (nucleic acids,
      proteins, xenobiotics) directly from crude samples. Several magnetic separation
      procedures have been developed to isolate target cells specifically. The purpose
      of this short review is to summarize various methodologies, strategies and
      materials which can be employed for the selection and separation of target cells
      with the help of magnetic field and thus to help the novices in this field to be
      able to orient themselves in vast amount of literature available. Immunomagnetic
      separations employing specific antibodies to label the target cells represent the
      most often used approach and are discussed in detail.

PMID- 10068133
TI  - Advances in cell separation: recent developments in counterflow centrifugal
      elutriation and continuous flow cell separation.
AB  - Cell separation by counterflow centrifugal elutriation (CCE) or free flow
      electrophoresis (FFE) is performed at lower frequency than cell cloning and
      antibody-dependent, magnetic or fluorescence-activated cell sorting.
      Nevertheless, numerous recent publications confirmed that these physical cell
      separation methods that do not include cell labeling or cell transformation
      steps, may be most useful for some applications. CCE and FFE have proved to be
      valuable tools, if homogeneous populations of normal healthy untransformed cells
      are required for answering scientific questions or for clinical transplantation
      and cells cannot be labeled by antibodies, because suitable antibodies are not
      available or because antibody binding to a cell surface would induce the cell
      reaction which should be investigated on purified cells or because antibodies
      bound to the surface hamper the use of the isolated cells. In addition, the
      methods are helpful for studying the biological reasons for, or effects of,
      changes in cell size and cellular negative surface charge density. Although the
      value of the methods was confirmed in recent years by a considerable number of
      important scientific results, activities to further develop and improve the
      instruments have, unfortunately, declined.

PMID- 10068134
TI  - Surface affinity chromatography of human peripheral blood cells.
AB  - Column packings with chemically bonded polyethylene glycol (PEG) and
      polypropylene glycol (PPG) were prepared and the separation of human peripheral
      blood cells by an aqueous polymeric two phase system could be performed in a
      partition chromatography. In this chromatographic system, the interaction of
      blood cells with bonded PEG, PPG stationary phases is apparently selective, and
      granulocytes and lymphocytes are more strongly retained on the column than
      erythrocytes and platelets. The hydrophobic interactions between the hydrophobic
      region on the cell surface membrane and the bonded PEG, PPG phases is probably
      the main factor affecting the retention of lymphocytes and granulocytes. The
      selective separation of human peripheral platelets, granulocytes and lymphocytes
      was investigated using another type of column packing bonded with
      methoxyethoxymethyl (MEM) groups. The isolation of platelets and lymphocytes from
      human leukocyte-rich plasma was performed with a MEM-Sephadex column and elution
      with 0.27 M sucrose solution. Platelets could be selectively collected from the
      same column by elution with 0.31 M methyl-alpha-D-mannoside at the high recovery
      of 100%.

PMID- 10068135
TI  - Subcellular fractionation, electromigration analysis and mapping of organelles.
AB  - Subcellular fractionation has provided the means required to analyze the
      composition and properties of purified cellular elements. In particular,
      subcellular fractionation has helped to define membrane boundaries and became
      necessary for the development of cell-free assays that reconstitute complicated
      cellular processes. Although cell fractionation techniques have improved over the
      last decades the purification of organelles to homogeneity is still a barely
      accessible goal in cell biology. In this article, we will first briefly review
      the basic principles of subcellular fractionation, and the establishment of
      different organelle fractions by density centrifugation, using tissue culture
      cells as a paradigm. Then we will discuss some of the intrinsic problems and will
      compare gradient purification of cellular extracts with electromigration
      analysis. Finally, we will describe alternative approaches, such as
      immunoisolation and flow cytometry to purify organelles from tissue culture
      cells.

PMID- 10068136
TI  - Chromatographic approaches to liposomes, proteoliposomes and biomembrane
      vesicles.
AB  - Size-exclusion chromatography has been used for fractionation of liposomes,
      proteoliposomes and biomembrane vesicles of up to approximately 500 nm in size
      and for separation of these entities from smaller components. Liposome sizes,
      encapsulation stability, and solute affinities for membrane proteins have been
      determined. Counter-current distribution in aqueous two-phase systems has widened
      the range of applications to larger structures. Immobilized biomembrane vesicles
      and (proteo)liposomes provide stationary phases for chromatographic analysis of
      specific or nonspecific membrane-solute interactions.

PMID- 10068137
TI  - Separation of plant membranes by electromigration techniques.
AB  - The review focuses on the multiple separating regimes that offers the free flow
      electrophoresis technique: free flow zone electrophoresis, isoelectric focusing,
      isotachophoresis, free flow step electrophoresis. Also, the feasibility to apply
      either interval or continuous flow electrophoresis is evaluated. The free flow
      zone electrophoresis regime is generally selected for the separation of cells,
      organelles and membranes while the other regimes find their largest fields of
      applications in the purification of proteins and peptides. The latter regimes
      present the highest resolution efficiency. Therefore, a large part of this review
      is devoted to the applicabilities of these different regimes to the purification
      of organelles and membrane vesicles at the preparative scale. Recent
      developments, both in instrumentation and procedures, are described. The major
      achievements in plant membrane fractionation obtained with free flow
      electrophoresis are outlined. The related procedures are both analytical and
      preparative: they separate tonoplast and plasma membrane simultaneously from the
      same homogenate, they discriminate for one type of membrane vesicles of opposite
      orientation, and process large quantities of membrane material by reason of the
      continuous flow mode. Recent advances using electromigration techniques that
      permit confirmation of the dynamic state of membranes, characterisation of
      complex membrane-dependent functions and discovery of new membrane-localised
      activities are presented.

PMID- 10068138
TI  - Electromigration for separations of protein complexes.
AB  - This paper describes electromigration of complexes, consisting of two or more
      proteins and non-covalently associated peptides. Relatively small complexes (Mr <
      1000000) can be resolved in sieving matrices. Large complexes are separated in
      free liquid systems. Examples of separation are given using native gels,
      denaturing gels and special formats thereof: blue native PAGE and gels
      incorporating a transversal temperature gradient. Both preparative and analytical
      applications are discussed as well as separations leading to mechanistic models
      of protein interaction. Carrier-free electrophoresis is represented by capillary
      zone electrophoresis, free-flow electrophoresis and density gradient
      electrophoresis. Emphasis is put on the free liquid separation of clathrin-coated
      vesicles and proteasomes.

PMID- 10068139
TI  - Purification of chaperonins.
AB  - The availability of protein samples of sufficient quality and in sufficient
      quantity is a driving force in biology and biotechnology. Protein samples that
      are free of critical contaminants are required for specific assays. Large amounts
      of highly homogeneous and reproducible material are needed for crystallography
      and nuclear magnetic resonance studies of protein structure. Protein-based
      therapeutic factors used in human medicine must not contain any contaminants that
      might interfere with treatment. The roles played by molecular chaperones in
      protein folding and in many cellular processes make these proteins very
      attractive candidates as biochemical reagents, and the class of chaperones called
      chaperonins is one of the most important candidates. Methods for successfully
      purifying chaperonins are needed to advance the field of chaperonin-mediated
      protein folding. This article outlines the strategies and methods used to obtain
      pure chaperonin samples from different biological sources. The objective is to
      help new researchers obtain better quality samples of chaperonins from many new
      organisms.

PMID- 10068140
TI  - Advances in the separation of bacteriophages and related particles.
AB  - Nondenaturing gel electrophoresis is used to both characterize multimolecular
      particles and determine the assembly pathways of these particles.
      Characterization of bacteriophage-related particles has yielded strategies for
      characterizing multimolecular particles in general. Previous studies have
      revealed means for using nondenaturing gel electrophoresis to determine both the
      effective radius and the average electrical surface charge density of any
      particle. The response of electrophoretic mobility to increasing the magnitude of
      the electrical field is used to detect rod-shaped particles. To increase the
      capacity of nondenaturing gel electrophoresis to characterize comparatively large
      particles, some current research is directed towards either determining the
      structure of gels used for electrophoresis or inducing steric trapping of
      particles in dead-end regions within the fibrous network that forms a gel. A
      trapping-dependent technique of pulsed-field gel electrophoresis is presented
      with which a DNA-protein complex can be made to electrophoretically migrate in a
      direction opposite to the direction of migration of protein-free DNA.

PMID- 10068141
TI  - Proteome analysis. I. Gene products are where the biological action is.
AB  - Two-dimensional electrophoresis has rapidly become the method of choice for
      resolving complex mixtures of proteins. Since the technique was pioneered in
      1975, 2-D gel methods have undergone a series of enhancements to optimize
      resolution and reproducibility. Recent improvements in the sensitivity of mass
      spectrometry have allowed the direct identification of polypeptides from 2-D gels
      by a procedure termed "mass profiling". In combination, these two techniques have
      made possible the characterization of the complete collection of gene products,
      or proteome, of an organism. Proteomes are increasingly being documented as
      interactive informational databases available on the World Wide Web (WWW). This
      availability of organismic global protein patterns will no doubt be an invaluable
      resource aiding the discovery of diagnostic and therapeutic disease markers.

PMID- 10068142
TI  - Proteome analysis. II. Protein subcellular redistribution: linking physiology to
      genomics via the proteome and separation technologies involved.
AB  - While annotated two-dimensional (2D) gel electrophoresis databases contain
      thousands of proteins, they do not represent the entire genome. High-molecular
      mass proteins in particular are conspicuously absent from such databases. Filamin
      is prototypical of this class of proteins since it is a dimer with relative
      molecular mass (Mr) of 520000 containing at least 240 potential phosphorylation
      sites. Filamin is not readily separated by current 2D procedures, and is
      difficult to study with respect to cycles of phosphorylation-dephosphorylation.
      Novel technologies are needed to identify biochemical pathways impinging upon
      such targets. The success of immunofluorescence microscopy as a research tool can
      be attributed in part to the fact that proteins redistribute in response to a
      variety of physiological stimuli. Comparable quantitative methods are required in
      proteome analysis. Three components are necessary for development of an approach
      that is capable of screening for protein redistribution events: (1) subcellular
      fractionation, (2) protein labeling and (3) data acquisition. An integrated
      approach is presented that utilizes differential detergent fractionation combined
      with reversible, luminescent protein stains and analytical imaging for high
      throughput analysis of signal transduction events leading to protein subcellular
      redistribution. The procedure has been successfully implemented to rapidly define
      key second messenger pathways leading to endothelial cell junctional permeability
      and to guide in the design of a new family of peptide-based anti-inflammatory
      drugs.

PMID- 10068143
TI  - Single cell gel electrophoresis assay: methodology and applications.
AB  - The single cell gel electrophoresis or Comet assay is a sensitive, reliable, and
      rapid method for DNA double- and single-strand breaks, alkali-labile sites and
      delayed repair site detection, in eukaryotic individual cells. Given its overall
      characteristics, this method has been widely used over the past few years in
      several different areas. In this paper we review the studies published to date
      about the principles, the basic methodology with currently used variations. We
      also explore the applications of this assay in: genotoxicology, clinical area,
      DNA repair studies, environmental biomonitoring and human monitoring.

PMID- 10068144
TI  - Isolation and separation of proteoglycans.
AB  - Proteoglycans contain a polypeptide core and an oligosaccharide chain composed of
      aminohexoses and uronic acid. The glycan chain is attached to the polypeptide in
      a bond to serine hydroxyl. The glycan chains may contain up to 200 disaccharide
      units and the proteoglycan molecular mass ranges from a few thousands to
      millions. Their physiological functions are related to barriers limiting
      diffusion across the membranes, articular lubrification, blood coagulation and
      cellular adhesion. The tissue proteoglycans can be extracted with 4 M guanidine
      hydrochloride and purified with chromatographic techniques. The soluble
      proteoglycans can be precipitated with cetylpyridinium chloride, purified by
      chromatography or by dialysis. All proteoglycan species are amenable to
      electrophoresis on polyacrylamide gels, and after blotting on polyvinylidene
      fluoride membranes, they can be stained for glycans. Proteoglycan analyses have
      shown their value in clinical mucopolysaccharidosis diagnostics, in occupational
      toxicology and in coagulation studies. Experimental applications include cell
      adhesion studies in tumor biology, regeneration in neurosciences or maturation of
      skin and kidneys.

PMID- 10068145
TI  - Methods for the differentiation of microorganisms.
AB  - Advances in analytical and diagnostic assays based on novel nucleic acid analyses
      techniques have revolutionized the application of molecular differentiation of
      microorganisms. Phenotypic typing schemes are now broadly supplemented by new
      genotyping methods which allow a more refined and detailed differentiation of
      closely related microorganisms, bacterial strains, isolates and pathogens on the
      DNA level. Bio-, sero- and phagetyping, antibiotic susceptibility tests,
      immunoblotting as well as multilocus enzyme- or polyacrylamide gel
      electrophoresis are now supported by the analysis of plasmid or chromosomal DNA
      restriction profiles, ribotyping, pulsed-field gel electrophoresis and polymerase
      or ligase-chain reaction-based methods or direct sequencing technique to
      differentiate microorganisms. Some of these molecular techniques are also used in
      the field of virology to analyse and differentiate closely related sub- or
      genotypes. Few examples for the analysis and investigation of these usually small
      genomes will also be given.

PMID- 10068146
TI  - Utilization of enzyme-substrate interactions in analytical chemistry.
AB  - Enzymes are capable of a highly specific interaction with a variety of substances
      including their respective substrates. This review summarizes how such
      interactions may be used in analytical (bio-)chemistry, e.g., for the elucidation
      of the binding mechanism, the determination of the binding strength, the carting
      of the binding site, or the screening of possible substrate/inhibitor molecules.
      Possible assay formats such as analytical affinity chromatography, affinity
      capillary electrophoresis (ACE), conventional affinity gel electrophoresis (AEP),
      and related techniques are discussed together with examples of recent
      applications. In addition a brief section on enzyme-substrate reactions as tools
      in analytical chemistry is included, since these are perhaps even more important
      to analytical (bio-)chemistry. The development and application of bioanalytical
      systems and especially biosensors in various fields including medicine,
      biotechnology, agriculture, defense and foodstuffs are considered.

PMID- 10068147
TI  - The cardiovascular effects of amperozide: interactions with cocaine.
AB  - Amperozide is a 5-HT2A receptor antagonist that significantly reduces the
      acquisition and expression, by rats, of a cocaine conditioned place preference.
      In order to rule out the possibility that amperozide affects a cocaine
      conditioned place preference due to effects on blood pressure or heart rate, the
      cardiovascular effects of amperozide were investigated. Alternating cumulative
      doses of amperozide (0.5, 1.0, 1.5 and 2.5 mg kg(-1)) or saline and phenylephrine
      (8 microg kg(-1)) were administered through the femoral vein of awake freely
      moving Sprague-Dawley rats and blood pressure and heart rate were recorded from
      the femoral artery. A single dose of cocaine (5.0 mg kg(-1)) was administered
      after all the amperozide or saline doses were given. Amperozide (0.5, 1.0, 1.5
      and 2.5 mg kg(-1)) did not have any significant effect on blood pressure compared
      to the saline control treatment to the same animals. However, 0.5 mg kg(-1)
      amperozide significantly decreased heart rate at 5 and 10 min. after
      administration. but higher doses did not further depress heart rate. Amperozide
      did not affect the increased blood pressure and decreased heart rate caused by
      phenylephrine. an alpha1-adrenoceptor agonist. In addition, amperozide did not
      affect the cardiovascular response to an intravenous dose of 5.0 mg kg(-1)
      cocaine. These results suggest that amperozide does not cause direct
      cardiovascular effects. The mechanism by which the lowest dose of amperozide
      caused a decrease in heart rate is unknown. Amperozide affects neither alpha
      adrenoceptor mediated vasoconstriction nor the increased sympathetic activity
      caused by the peripheral and central effects of cocaine. The significance of
      these results, in terms of locomotor activity and the cocaine conditioned place
      preference paradigm, is discussed.

PMID- 10068148
TI  - Modulation of drug-metabolising enzyme expression by condensation products of
      indole-3-ylcarbinol, an inducer in cruciferous vegetables.
AB  - Indole-3-ylcarbinol (13C) is formed during processing of cruciferous vegetables
      and is suggested to be one of the modulators of drug-metabolising enzymes. Indole
      3-ylcarbinol is a far less efficient inducer of hepatic enzymes after parenteral
      than after oral administration, due to formation of active metabolites in the
      gastrointestinal tract. As indole-3-ylcarbinol is unstable in weakly acidic
      aqueous solutions, non-active condensation products may be formed from indole-3
      ylcarbinol, that cannot be transformed to the active products when reaching the
      stomach. The purpose of the present study was to test the ability of the
      condensation products formed at a pH corresponding to that of fresh vegetable
      juice to modulate the metabolism of xenobiotics. Indole-3-ylcarbinol was
      incubated in vitro at room temperature in the dark at pH 5.5 and samples taken at
      various times, for oral administration to rats and for chemical analysis. Indole
      3-ylcarbinol was rapidly transformed into various oligomeric products. The 7
      ethoxyresorufin O-deethylase activities (marker of cytochrome Cytochrome P450 1A
      enzymes, CYP1A) in liver, kidney and colon increased with the duration of the in
      vitro condensation period whereas the formation of 6beta-, 15beta- and and 2alpha
      hydroxytestosterone was not affected significantly, indicating no effect on
      CYP2C11 or CYP3A enzymes. The hepatic metabolism of the food mutagen 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). was increased by indole-3
      ylcarbinol condensation products and the 4'-OH-PhIP/N-OH-PhIP ratio was decreased
      due to a significantly increased formation of the proximate genotoxic metabolite.
      N-OH-PhIP. The activities of DT-diaphorase and glutathione S-transferase were not
      changed significantly in the rat organs. These experiments clearly indicate that
      indole-3-ylcarbinol is not the definitive CYP1A inducer and that indole-3
      ylcarbinol at near-neutral pH, is transformed to compounds that are inducers by
      themselves or may be further converted into inducing compounds in the rat
      stomach. Also, the enzyme inducing potency of indole-3-ylcarbinol containing
      vegetable juice is apparently enhanced by incubation in vitro before the intake.

PMID- 10068149
TI  - Rat offspring treated prenatally with capsaicin do not show some of the
      irreversible effects induced by neonatal treatment with neurotoxin.
AB  - The present study evaluates whether some of the irreversible effects induced by
      neonatally administered capsaicin are present in offspring prenatally treated
      with the neurotoxin as well, and investigated its foetal toxicity. Capsaicin was
      administered subcutaneously at doses of 50, 100 and 200 mg/kg in five injections
      every other day between gestational days 7-15, the period of major organogenesis,
      or in a single subcutaneous injection of 50 mg/kg only at day 15 of gestation. In
      one-month old rats prenatally capsaicin-treated the response to noxious
      stimulation (hot plate and wiping tests) and the urinary excretion in response to
      oral water load were evaluated. Parallel experiments were conducted in one-month
      old rats treated with capsaicin (50 mg/kg) on the 2nd day of life. Prenatal
      capsaicin induced no evident treatment-related signs of toxicity in dams and
      offspring, nor did it influence the body growth of the pups or induce cutaneous
      lesions. Unlike neonatal treatment, prenatal administration of neurotoxin did not
      raise the threshold to thermal and chemical pain, and did not modify diuresis
      induced by oral load. Since researchers have proposed the existence of more than
      one population of capsaicin-sensitive afferent neurones which differ in their age
      dependent sensitivity to capsaicin, we hypothesized that failure of prenatal
      treatment might be due either to reduced foetal availability, not capable of
      selectively destroying capsaicin-sensitive neurones, or to incomplete
      rearrangement and maturation of developing primary sensory neurons, in fact, the
      existence is well known of more than one population of capsaicin-sensitive
      afferent neurons which differ in their age-dependent sensitivity to capsaicin.
      Future studies are needed to elucidate the effects of capsaicin at cellular and
      molecular levels.

PMID- 10068150
TI  - The effect of toremifene on bone and uterine histology and on bone resorption in
      ovariectomised rats.
AB  - The effect of the selective oestrogen receptor modulator, toremifene, to inhibit
      ovariectomy-induced bone loss was studied in rats. The oral doses were 0.3, 3.0
      or 30 mg/kg/day for 2 months. 17beta-oestradiol (5 microg/kg/day, subcutaneously)
      was used as positive control. One group was also treated with a combination of
      17beta-oestradiol (5 microg/kg) and toremifene (3.0 mg/kg). Biochemical markers
      were urinary hydroxyproline and calcium (adjusted with urinary creatinine levels)
      and the serum level of pyridinoline cross-linked carboxy terminal telopeptide, a
      bone specific collagen breakdown product. The femoral and sternal trabecular bone
      thickness served as histological parameters. Ovarectomy increased the levels of
      hydroxyproline and pyrodinoline and decreased the trabecular bone thickness
      compared to the sham-operated control group. This was inhibited by both test
      compounds but 17beta-oestradiol was more efficient. Toremifene did not reverse
      the ovariectomy-induced reduction of urinary calcium but inhibited the 17beta
      oestradiol-related increase. When administered together with oestradiol,
      toremifene did not reverse the positive effect of 17beta-oestradiol on bone,
      however toremifene reversed the oestradiol-related uterothrophic effects. These
      findings indicate that the antagonistic features of toremifene dominate in the
      rat uterus the agonistic properties do in the bone.

PMID- 10068151
TI  - The inhibitory effect of ambroxol on respiratory burst, degranulation and
      cytosolic Ca2+ change in degraded immunoglobulin G-activated neutrophils.
AB  - Superoxide and H2O2 production by neutrophils stimulated by 0.5 mg/ml degraded
      immunoglobulin G (IgG) and 1 microM N-formyl-methionyl-leucyl-phenylalanine
      (fMLP) was inhibited by ambroxol in a dose-dependent fashion, and at the
      concentration of 100 microM, 43.3% to 64.3% of inhibitions were detected. The
      inhibitory effect of ambroxol on H2O2 production by neutrophils was greater than
      that on superoxide production. The production of nitrite by lipopolysaccharide
      activated murine peritoneal macrophages was significantly attenuated by ambroxol
      in a dose-dependent fashion and NG-monomethyl-L-arginine (NMMA). Ambroxol
      decreased the release of myeloperoxidase and lysozyme evoked by 0.5 mg/ml
      degraded immunoglobulin G and 1 microM fMLP in a dose-dependent fashion, and at
      the concentration of 100 microM, 37.1% to 64.2% of inhibitions were observed. The
      stimulatory effect of phorbol 12-myristate 13-acetate (PMA) (0.1 microg/ml) on
      superoxide production and myeloperoxidase, which is inhibited by 100 nM
      staurosporine, was not affected by 100 microM ambroxol. Degraded immunoglobulin G
      (0.5 mg/ml) caused an immediate elevation of [Ca2+]i in fura-2 load neutrophils
      in 1.23 mM Ca2+-containing medium. Preincubation of neutrophils with 10 microM to
      100 microM ambroxol, 5 mM EGTA and 100 microM verapamil depressed the elevation
      of [Ca2+]i elicited by 0.5 mg/ml degraded immunoglobulin G. In conclusion, the
      inhibitory action of ambroxol on stimulated neutrophil responses, including
      respiratory burst and lysosomal enzyme release, appears to be attributed to its
      depressant action on the activation process, including the change in
      intracellular Ca2+ level. in which the role of protein kinase C is uncertain.

PMID- 10068152
TI  - Region-selective effects of long-term lithium and carbamazepine administration on
      cyclic AMP levels in rat brain.
AB  - The effect of lithium and carbamazepine in the treatment of bipolar affective
      disorder is well established. Although a number of biochemical effects have been
      found, the exact molecular mechanisms underlying their therapeutic actions have
      not been elucidated nor are the target regions in the brain identified. Taken
      into account the important role of the cyclic AMP second messenger system in the
      regulation of neuronal exitability and the indications of its involvement in the
      patophysiology of bipolar affective disorder, we have focused on the drug effects
      on cyclic AMP levels. The objectives of this investigation were to measure the
      effects on basal cyclic AMP levels, and to locate target regions within the rat
      brain after long-term administration of lithium and carbamazepine. Drug
      treatments were carried out for a period of 28 days. After either drug treatment
      the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in
      hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostriatum
      the cyclic AMP level was decreased to about 30% after treatment with lithium. We
      suggest the common region-selective effect, observed for both drugs in frontal
      cortex, to be essential for the therapeutic actions of lithium and carbamazepine.

PMID- 10068153
TI  - Interactions of buspirone with itraconazole and rifampicin: effects on the
      pharmacokinetics of the active 1-(2-pyrimidinyl)-piperazine metabolite of
      buspirone.
AB  - The effects of inhibition and induction of the metabolism of buspirone on the
      plasma concentrations of 1-(2-pyrimidinyl)-piperazine (a piperazine metabolite),
      the principal active metabolite of buspirone, were investigated. Two separate
      randomized, placebo-controlled cross-over studies with two phases were carried
      out in healthy volunteers. In Study I, six subjects took itraconazole 200 mg
      daily or matched placebo orally for 4 days. On day 4, 10 mg buspirone was
      administered orally. In study II, six subjects took rifampicin 600 mg daily or
      matched placebo orally for 5 days. On day 6, 30 mg buspirone was administered
      orally. Buspirone and piperazine metabolite concentrations in plasma were
      determined by gas chromatography. Itraconazole decreased the mean AUC of the
      piperazine metabolite by 50% (P<0.05) and the Cmax by 57% (P<0.05) compared with
      placebo, whereas the mean AUC and Cmax of unchanged buspirone were increased 14.5
      fold (P<0.05) and 10.5-fold (P<0.05), respectively, by itraconazole. Rifampicin
      had no significant effect on the AUC of the piperazine metabolite, but it
      increased the mean Cmax of the piperazine metabolite by 35% (P=0.08). The mean
      AUC and Cmax of parent buspirone were reduced by 91% (P<0.05) and 85% (P<0.05),
      respectively, by rifampicin. The mean ratio of the AUC of the piperazine
      metabolite to that of buspirone was decreased 34-fold (P<0.05) by itraconazole
      and increased 7.6-fold (P<0.05) by rifampicin. In conclusion, itraconazole and
      rifampicin caused only relatively minor changes in the plasma concentrations of
      the active piperazine metabolite of buspirone, although they had drastic effects
      on the concentrations of parent buspirone.

PMID- 10068154
TI  - Effects of trifluralin on Trypanosoma cruzi in vitro and in vivo.

PMID- 10068155
TI  - The cortical representation of pain.
AB  - Anatomical and physiological studies in animals, as well as functional imaging
      studies in humans have shown that multiple cortical areas are activated by
      painful stimuli. The view that pain is perceived only as a result of thalamic
      processing has, therefore, been abandoned, and has been replaced by the question
      of what functions can be assigned to individual cortical areas. The following
      cortical areas have been shown to be involved in the processing of painful
      stimuli: primary somatosensory cortex, secondary somatosensory cortex and its
      vicinity in the parietal operculum, insula, anterior cingulate cortex and
      prefrontal cortex. These areas probably process different aspects of pain in
      parallel. Previous psychophysical research has emphasized the importance of
      separating pain experience into sensory-discriminative and affective-motivational
      components. The sensory-discriminative component of pain can be considered a
      sensory modality similar to vision or olfaction; it becomes more and more evident
      that it is subserved by its own apparatus up to the cortical level. The affective
      motivational component is close to what may be considered 'suffering from pain';
      it is clearly related to aspects of emotion, arousal and the programming of
      behaviour. This dichotomy, however, has turned out to be too simple to explain
      the functional significance of nociceptive cortical networks. Recent progress in
      imaging technology has, therefore, provided a new impetus to study the multiple
      dimensions of pain.

PMID- 10068156
TI  - Dynamic mechanical allodynia in humans is not mediated by a central presynaptic
      interaction of A beta-mechanoreceptive and nociceptive C-afferents.
AB  - Recently, Cervero and Laird (NeuroReport, 7 (1996) 526-528; Pain, 68 (1996) 13
      23) proposed a new pathophysiological mechanism of dynamic mechanical allodynia
      in skin. Using the capsaicin pain model in humans, they showed that light
      mechanical stimulation within an area of secondary mechanical allodynia induces
      vasodilatation measured by laser-Doppler flowmetry. They suggested that the low
      threshold A beta-mechanoreceptive fibres depolarize the central terminals of
      nociceptive primary afferent neurons via interneurons. Consequently, the
      vasodilatation is produced by impulses conducted antidromically in nociceptive C
      axons. The allodynia was proposed to result from depolarization of central
      terminals of primary afferent neurons with C-fibres with activation of
      nociceptive dorsal horn neurons. In order to extend these findings, we used the
      same experimental approach but additionally stimulated the A beta-fibres
      electrically to evoke secondary allodynia during simultaneous monitoring skin
      blood flow. Twenty microlitres of a 0.5% capsaicin solution was injected
      intradermally into the dorsal forearm. Skin sites that demonstrated dynamic
      mechanical allodynia but were not located within the area of primary hyperalgesia
      and flare were investigated. Ten mm away from a laser-Doppler probe, dynamic
      mechanical allodynia was induced for 1 min (1) by moving a cotton swab and (2) by
      electrically stimulating the afferent nerve endings transdermally. Increasing
      stimulus intensities were applied (0.3-4 mA, 40 Hz, pulse duration 0.2 ms). After
      intracutaneous injection of capsaicin, light mechanical stimulation elicited a
      burning painful sensation (numeric analogue scale (NAS) 1.5-3) and concomitant
      movement artefacts at the laser signal. Antidromic vasodilatation was never
      observed. In this area of dynamic allodynia, electrical stimulation at stimulus
      intensities that were not painful before capsaicin injection (A beta-stimulation)
      was now able to elicit a burning painful sensation (NAS 1.5-3). No change in
      blood flow was detected. When the stimulus intensities were increased reaching
      levels that were also painful before capsaicin treatment (C-fibre stimulation),
      an increase in blood flow could be induced showing the time course of an axon
      reflex vasodilatation. In conclusion, electrical stimulation of A beta-fibres in
      allodynic skin does not induce antidromic vasodilatation. Consequently,
      interaction of A beta-mechanoreceptive fibres and nociceptive C-fibres at a
      presynaptic level is unlikely to produce antidromically conducted impulses and
      therefore cannot explain the pathophysiology of mechanical allodynia.
      Alternatively, it is much more likely that under pathophysiological conditions,
      activity in A beta-fibres may activate nociceptive second-order neurons, i.e. in
      the spinal cord.

PMID- 10068157
TI  - Pain related undergraduate teaching in medical faculties in Finland.
AB  - The present questionnaire study was conducted to examine how teachers in all
      Finnish medical faculties have included pain teaching in their courses for
      undergraduate medical students. The study was planned to compare the existing
      education in Finland with the IASP curriculum on pain for medical schools. In
      1991 and 1995 the questionnaire was sent to a total of 135 and 130 university
      teachers, respectively. The teachers were asked about the quantity and quality of
      their pain teaching. Teachers' attitudes on pain related teaching were also
      examined. A Finnish translation of the IASP curriculum was provided, and
      university teachers were asked to evaluate it and compare it with their current
      teaching. The educational programs of all universities were also analyzed. After
      completion of these surveys, representatives of teachers responsible for teaching
      of pain, and of medical students from all Finnish medical faculties were invited
      to a meeting to discuss methods for improving and developing education. Completed
      questionnaires were received from 107 university teachers (78%) in 1991 and from
      74 (60%) in 1995. No printed curricula for pain education were found in any
      university and in all universities pain teaching was provided in an inconsistent
      way. There were differences, yet statistically non-significant, between the
      faculties in the pain teaching. No major differences were observed between the
      two questionnaires. A serious lack of teaching in psychology of pain was a
      general finding. University teachers were found to have positive attitudes
      towards developing their teaching of pain. The IASP curriculum has not been fully
      followed but was considered a valuable tool in planning the educational programs.
      The curriculum should be distributed directly to the governmental bodies of the
      universities, since individual university teachers are not necessarily familiar
      with it. Local associations may have an important role in this distribution as we
      have shown. This report shows the necessity of changing the attitudes of
      university teachers providing concrete teaching programs for pain. A multimedia
      package of pain containing references, video tapes and cd-discs produced by a
      workshop of IASP would certainly be welcome.

PMID- 10068158
TI  - Lack of involvement of capsaicin-sensitive primary afferents in nerve-ligation
      injury induced tactile allodynia in rats.
AB  - Tactile allodynia and thermal hyperalgesia, two robust signs of neuropathic pain
      associated with experimental nerve injury, have been hypothesized to be
      mechanistically distinguished based on (a) fiber types which may be involved in
      the afferent input, (b) participation of spinal and supraspinal circuitry in
      these responses, and (c) sensitivity of these endpoints to pharmacological
      agents. Here, the possibility that nerve-injury induced tactile allodynia and
      thermal hyperalgesia may be mediated via different afferent fiber input was
      tested by evaluating these responses in sham-operated or nerve-injured (L5/L6)
      rats before or after a single systemic injection of resiniferatoxin (RTX), an
      ultrapotent analogue of the C-fiber specific neurotoxin, capsaicin. Tactile
      allodynia, and three measures of thermal nociception, tail-flick, paw-flick and
      hot-plate responses, were determined before and at various intervals for at least
      40 days after RTX injection. Nerve-injured, but not sham-operated, rats showed a
      long-lasting tactile allodynia and thermal hyperalgesia (paw-flick) within 2-3
      days after surgery; responses to other noxious thermal stimuli (i.e., tail-flick
      and hot-plate tests) did not distinguish the two groups at the stimulus
      intensities employed. RTX treatment resulted in a significant and long-lasting
      (i.e. essentially irreversible) decrease in sensitivity to thermal noxious
      stimuli in both sham-operated and nerve-injured rats; thermal hyperalgesia was
      abolished and antinociception produced by RTX. In contrast, RTX treatment did not
      affect the tactile allodynia seen in the same nerve-injured rats. These data
      support the concept that thermal hyperalgesia seen after nerve ligation, as well
      as noxious thermal stimuli, are likely to be mediated by capsaicin-sensitive C
      fiber afferents. In contrast, nerve-injury related tactile allodynia is
      insensitive to RTX treatment which clearly desensitizes C-fibers and, therefore
      such responses are not likely to be mediated through C-fiber afferents. The
      hypothesis that tactile allodynia may be due to inputs from large (i.e. A beta)
      afferents offers a mechanistic basis for the observed insensitivity of this
      endpoint to intrathecal morphine in this nerve-injury model. Further, these data
      suggest that clinical treatment of neuropathic pains with C-fiber specific agents
      such as capsaicin are unlikely to offer significant therapeutic benefit against
      mechanical allodynia.

PMID- 10068159
TI  - Mechanical hyperalgesia after spinal nerve ligation in rat is not reversed by
      intraplantar or systemic administration of adrenergic antagonists.
AB  - The development of alpha-adrenergic sensitivity in cutaneous nociceptors has been
      postulated as a mechanism for sympathetically maintained pain (SMP). In order to
      characterize the adrenergic receptors involved, we investigated the effects of
      intraplantar administration of alpha1-(prazosin) and alpha2-(yohimbine)
      adrenergic antagonists and systemic injection of phentolamine, a non-specific
      alpha-adrenergic blocker, on allodynic/hyperalgesic behavior in an animal model
      thought to mimic SMP in humans. Peripheral neuropathy in rats was induced by
      tight ligation of the L5/L6 spinal nerves. Mechanical hyperalgesia was quantified
      with von Frey hairs applied either for 3 s or repetitively to the plantar surface
      of the hindpaw. Responses to the 3 s duration stimulus were used to determine the
      paw withdrawal threshold with the up-down paradigm and repetitive stimuli were
      used to determine the response incidence of paw withdrawal to a given von Frey
      hair. Mechanical thresholds on the ipsilateral paw decreased significantly after
      ligation and were stable over the following 3 weeks. Intradermal administration
      of yohimbine or prazosin did not significantly alleviate mechanical hyperalgesia
      in L5/L6 ligated animals. Also systemic administration of phentolamine (1 and 5
      mg/kg) did not alleviate the increased incidence of paw withdrawal in L5/L6
      spinal nerve ligated animals. These results suggest that an alpha adrenergic
      interaction between sympathetic efferent and somatic afferent fibers does not
      play a critical role for the maintenance of mechanical hyperalgesia in this model
      for neuropathic pain.

PMID- 10068160
TI  - Lumbar sympathectomy failed to reverse mechanical allodynia- and hyperalgesia
      like behavior in rats with L5 spinal nerve injury.
AB  - The L5 spinal nerve ligation model of neuropathic pain in rats has been proposed
      as a model for sympathetically maintained pain (SMP) based on the effects of
      surgical or chemical sympathectomy on nerve injury induced behavior. In an
      attempt to confirm that the lesion produces an animal model of SMP, surgical
      sympathectomies were independently conducted in two different laboratories (Johns
      Hopkins and University Kiel) using male Sprague-Dawley (n = 30) or Wistar rats (n
      = 14). The L5 spinal nerve was ligated or cut and ligated. Using von Frey hairs,
      paw withdrawal threshold and incidence of paw withdrawal were tested concurrently
      before and after the sympathectomy. The sympathectomy was either verified by (a)
      glyoxylic acid staining of peripheral blood vessels of the hindpaw or (b) skin
      temperature measurements of the hindpaws. To blind the experimenter, surgeries
      and behavioral tests were performed by two different investigators and a sham
      sympathectomy was performed at Johns Hopkins. Decreased paw withdrawal thresholds
      and increased frequencies of paw withdrawal on the lesioned side were observed
      after the L5 lesion. Thus, the L5 spinal nerve ligation resulted in behavioral
      signs of allodynia and hyperalgesia to mechanical stimuli. Lumbar surgical
      sympathectomy 1-3 weeks after the lesion or prior to lesion with bilateral
      removal of the sympathetic ganglia L2-L4, however, did not reverse or prevent the
      behavioral changes induced by the nerve injury. The lack of effect of the
      sympathectomies was independent of the testing paradigm used. Experiments in
      Wistar and Sprague-Dawley rats yielded the same results. Potential reasons for
      the discrepancies between the present study and earlier reports are discussed.
      These results indicate that an L5 spinal nerve injury rat model is not a reliable
      model for SMP.

PMID- 10068161
TI  - The effects of disclosure on pain during dental hygiene treatment: the moderating
      role of catastrophizing.
AB  - Catastrophizers and non-catastrophizers were asked to disclose about their dental
      worries prior to undergoing dental hygiene treatment. It was hypothesized that
      the effects of emotional disclosure would vary as a function of the level of
      catastrophizing; where catastrophizers would be more likely than non
      catastrophizers to show reductions in pain and emotional distress. The study also
      examined whether emotional disclosure influenced subsequent levels of
      catastrophizing and dental anxiety. Eighty undergraduate students were randomly
      assigned to a disclosure condition or a control condition prior to undergoing a
      scaling and root planing procedure. In the control condition, catastrophizers
      reported significantly more pain and emotional distress than non-catastrophizers.
      In the disclosure condition, catastrophizers and non-catastrophizers did not
      differ significantly in their pain and emotional distress. The interaction
      between condition and level of catastrophizing remained significant even when
      controlling for emotional distress and the emotional content of the thought
      records. While catastrophizers benefited from disclosure in regard to their
      immediate physical and emotional experience, their levels of catastrophizing and
      dental anxiety remained essentially unchanged. Theoretical and clinical
      implications of the findings are discussed.

PMID- 10068162
TI  - Spatial and temporal summation of sensory and affective dimensions of deep
      somatic pain.
AB  - There is considerable evidence in support of differential information processing
      of the sensory-discriminative and motivational-affective meanings of pain. The
      purpose of this work was to examine whether temporal (acute, tonic, persistent)
      and spatial (local, regional, widespread) aspects of deep somatic pain influence
      the sensory and affective dimensions of pain. Acute pain consisted of a short
      bout of pain, lasting about 100 s. Tonic pain was the experience of
      experimentally maintained pain for 18 min. Both acute and tonic pain were induced
      by infusion of an algesic or control substance into muscle with the subject
      blinded with respect to the type of infusion and randomization of the application
      sequence. Comparing the response of experimental subjects to a group of matched
      cases with persistent masticatory myalgia alone or in combination with widespread
      musculoskeletal pain, we examine whether the experimental state is different from
      the matched clinical condition, and whether there is a difference between the
      condition being restricted to the face or not. The McGill pain questionnaire was
      used to assess the sensory and affective correlates of pain. The normalized
      sensory score for acute/unilateral face pain was different from that established
      for tonic/unilateral face pain (P = 0.055, borderline s.), and so was the
      normalized affective score (P = 0.009, s.). When comparing tonic/unilateral
      versus tonic/bilateral face pain, the affective scores increased with increased
      pain involvement (P = 0.009, s.) while the sensory sores were unaffected by the
      additional pain induced in the contralateral masseter muscle (P = 0.357, n.s).
      Notably, sensory and affective scores for tonic/bilateral and
      persistent/bilateral face pain were not statistically different (sensory: P =
      0.169, n.s.; affective: P = 0.643, n.s). On the other hand, when contrasting
      persistent/bilateral face pain with persistent/ widespread musculoskeletal pain,
      both scores were significantly different (sensory: P < 0.001, s.; affective: P =
      0.041, s.). Time in and spread of pain influenced the perceptual correlates of
      pain to a significant degree. The major increase in the sensory dimension
      occurred from 'no pain' to 'acute pain'. Affective scores showed the most
      significant increases from acute to tonic pain, particularly with greater spatial
      involvement. The significant increases in sensory scores observed when
      contrasting persistent facial pain alone and in combination with widespread
      musculoskeletal pain was attributed to the broader body experience. Because the
      perceptual correlates of tonic and matched persistent (chronic) pain states were
      similar, we concluded that it does not require months for the development of the
      sensory and affective meaning of persistent pain as assumed.

PMID- 10068163
TI  - Effects of kappa opioids in the inflamed rat colon.
AB  - The objective of this study was to examine the antinociceptive effects of
      peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of
      inflammatory bowel disease produced by intracolonic instillation of
      trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine)
      and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model
      of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80)
      on responses of pelvic nerve afferent fibers innervating the colon were also
      tested. In the behavioral study, systemic injections of morphine and both kappa
      ORAs dose-dependently inhibited the visceromotor response to colorectal
      distension in rats with uninflamed or inflamed colons. The inhibitory effects of
      kappa-ORAs, but not morphine, were significantly greater in rats with colons
      inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg)
      of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not
      of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC
      80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs
      dose-dependently inhibited responses of pelvic nerve afferent fibers with
      significantly greater potency in the inflamed colon. Pretreatment with a non
      opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in
      the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in
      the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid
      receptors in colonic inflammation.

PMID- 10068164
TI  - Alterations in neuropeptide Y, tyrosine hydroxylase, and Y-receptor subtype
      distribution following spinal nerve injury to rats.
AB  - Recent animal models of experimental nerve injury have proven useful in
      evaluating potential sympathetic involvement in neuropathic pain syndromes. We
      have employed a widely adopted unilateral L5/L6 spinal nerve ligation model to
      compare the development of mechanical allodynia with neurochemical changes both
      at the site of peripheral nerve injury and in the dorsal root ganglia (DRG). We
      have focused on the expression of neuropeptide Y (NPY), a well-studied regulatory
      peptide and phenotypic marker of sympathetic neurons, and functionally related Y
      receptor binding sites following nerve injury. In sympathetic neurons, NPY is
      colocalized and coreleased with norepinephrine (NE) at peripheral sites of
      action. Furthermore, NPY gene expression is induced within the population of
      medium- and large-diameter DRG neurons of the A beta-fiber class after
      experimental nerve injury. We therefore hypothesized that concurrent alterations
      in NPY and NE expression by sympathetic and sensory neurons may be a contributing
      factor to sympathetically-maintained neuropathic conditions. Animals with
      unilateral L5/L6 spinal nerve ligation developed mechanical allodynia of the hind
      paw ipsilateral to the site of injury that persisted until sacrifice at
      postoperative day 10. A significant induction of preproneuropeptide Y-encoding
      (PPNPY) mRNA, as detected by in situ hybridization histochemistry (ISHH),
      occurred in populations of medium- and large-diameter DRG neurons ipsilateral to
      the site of injury. Immunohistochemical analysis indicated a marked decline in
      the number of labeled sympathetic axons positive for tyrosine hydroxylase-like
      and NPY-like immunoreactivities (TH-LI and NPY-LI, respectively) proximal to the
      site of nerve injury and almost complete elimination of immunopositive fibers
      distal to the site of ligation. Whereas, the extent of colocalization of NPY-LI
      to TH-LI-positive sympathetic axons in unaffected L4 or L5 nerve segments
      exceeded 80%, this figure declined to approximately 50% in regenerating axons of
      ligated spinal nerve L5. The portion of NPY-LI that was not colocalized to
      sympathetic TH-LI-positive fibers was most likely contributed by regenerating
      sensory axons, consistent with marked de novo synthesis of NPY by DRG neurons. In
      end bulb axon terminals, i.e. morphological profiles characteristic of neuromas,
      NPY-LI-positive elements that were not colocalized to TH-LI-positive sympathetic
      elements appeared to be spatially segregated from those of sympathetic origin
      with colocalized TH-LI and NPY-LI. Receptor autoradiography indicated that small-
      and medium-diameter DRG somata of the C-fiber class normally express both Y1 and
      Y2 receptor subtypes. The pattern of the distribution of Y-receptor binding sites
      appeared to be relatively unaffected by spinal nerve ligation. In contrast, there
      was a marked increase in the density of Y2 receptor binding sites in the proximal
      segment of ligated spinal nerve L5, consistent with previously published data
      indicating differential transport of the Y2 autoregulatory receptor subtype to
      nerve terminals. Induction of NPY gene expression in injured DRG neurons is
      consistent with appearance of NPY-LI-positive end bulbs derived from regenerating
      sensory axons that are found in developing neuromas containing a relatively high
      density of transported prejunctional Y2 receptors. Newly established functional
      interactions of spatially segregated sensory- and sympathetically-derived end
      bulbs in developing neuromas may enhance neuronal hyperexcitability engendered by
      aberrant electrical activity at the site of injury. Injury-related alterations in
      the regulatory activities of NPY released within the DRG at somally-distributed Y
      receptors may also contribute to the development and/or persistence of symptoms
      characteristic of sympathetically-maintained pain. Finally, at later times NPY
      mediated modulation of NE release from invading sympathetic axon terminals within
      the DRG may affect the extent of alpha2 rece

PMID- 10068165
TI  - Muscle hardness in patients with chronic tension-type headache: relation to
      actual headache state.
AB  - It has recently been reported that the pericranial muscles in patients with
      chronic tension-type headache are harder, i.e. have a higher consistency, than in
      controls. The primary aim of the present study was to investigate whether muscle
      hardness is influenced by the presence or absence of actual headache and whether
      hardness is correlated to tenderness. The secondary aim was to compare muscle
      hardness between patients and healthy controls. Hardness of the trapezius muscle
      was measured with a hardness meter in 20 patients with chronic tension-type
      headache and in 20 healthy controls. The patients were examined on 2 days, 1 day
      with headache and 1 day without headache. Pericranial myofascial tenderness was
      recorded with manual palpation. In addition, muscle hardness was measured in
      another five patients out-side headache and in 30 healthy controls. The muscle
      hardness recorded in patients (n = 20) on days with headache, 98 +/- 26 kPa/cm,
      did not differ significantly from the muscle hardness recorded on days without
      headache, 100 +/- 21 kPa/cm, (P = 0.62). The muscle hardness was positively
      correlated to the local tenderness score recorded from the trapezius muscle both
      on days with headache (R = 0.52, P = 0.02) and on days without headache (R =
      0.53, P = 0.02). The total tenderness score (TTS) recorded in patients on days
      with headache, 23 +/- 10, was significantly higher than the TTS recorded on days
      without headache, 15 +/- 11, (P = 0.0001). There was a significant difference
      between the TTS recorded in patients without headache, 15 +/- 11, and in
      controls, 4 +/- 4, (P = 0.002). The muscle hardness was significantly higher in
      patients on days without headache (n = 25), 97 +/- 20 kPa/cm, than in controls (n
      = 30), 87 +/- 16 kPa/cm (P = 0.03). On basis of previous and present results, we
      suggest that muscle hardness and muscle tenderness are permanently altered in
      chronic tension-type headache and not only a consequence of actual pain. In
      addition, the positive correlation between muscle hardness and tenderness
      supports the common clinical observation that tender muscles are harder than
      normal muscles.

PMID- 10068166
TI  - Postoperative pain assessment and management in adolescents.
AB  - A 3-year study investigated the experience and management of postoperative pain
      following elective surgery in an adolescent sample, using a variety of valid,
      reliable instruments and semi-structured interviews. In addition to the
      adolescent subjects, the views of one parent of each adolescent were sought and a
      sample of health professionals comprising surgeons, anaesthetists and nurses were
      interviewed about acute pain in adolescent patients. This paper presents some of
      the main findings pertaining to pain assessment and management. Pain, experienced
      by most adolescents on the 1st and 3rd postoperative days, was influenced by the
      presence of anxiety and depression, in addition to the maturational stage;
      differences between in-patients and day cases are highlighted. Recommendations
      for practice include the need for more effective pain management and raising
      awareness of the importance of both psychological state and adjustment to
      adolescence in this age-group.

PMID- 10068167
TI  - Morphine-induced analgesia in rats withdrawn from concurrent nimodipine and
      morphine treatment.
AB  - The effect of repeated administration of dihydropyridine calcium channel
      antagonist, nimodipine, given concurrently with morphine on the development of
      tolerance to the antinociceptive actions of morphine in rats was studied. In
      acute experiments nimodipine (1 mg/kg i.p.) enhanced the antinociceptive effect
      of morphine (2.5 mg/kg s.c.) in the hot-plate and tail immersion tests. Daily
      administration of morphine either for 10 days (increasing the daily dose from 20
      to 35 mg/kg) or for 24 days (increasing the daily dose from 20 to 70 mg/kg)
      induced tolerance to the antinociceptive effect of a challenge dose of morphine
      (10 mg/kg) administered 24 h after the withdrawal from chronic morphine.
      Concurrent administration of nimodipine (1 mg/kg per day) with morphine for 10 or
      24 days augmented the reduction of the antinociceptive effect of morphine.
      Neither acute nor repeated administration of nimodipine with morphine altered the
      concentrations of morphine or its metabolite morphine 6-glucuronide in the brain
      tissue or in the plasma. The observed further reduction in the nociceptive
      response in morphine tolerant animals pre-treated with nimodipine is, most
      probably, due to the adaptive changes in the central dihydropyridine calcium
      channels induced by the withdrawal from repeated nimodipine treatment.

PMID- 10068168
TI  - Spinal cord stimulation attenuates dorsal horn neuronal hyperexcitability in a
      rat model of mononeuropathy.
AB  - The mechanisms underlying the relief of neuropathic pain of peripheral origin by
      spinal cord stimulation (SCS) are poorly understood. The present study was
      designed to investigate the effects of SCS on evoked and spontaneous discharges
      in dorsal horn neurons in intact and in nerve-injured rats subjected to partial
      sciatic nerve ligation according to Seltzer et al. (1990). Tactile sensitivity in
      the hind paw was assessed in behavioral tests using von Frey filaments. The
      presence of 'allodynia' was defined as a withdrawal response to a filament of 10
      g or less. Under halothane/oxygen anesthesia the effects of SCS (50 Hz, 0.2 ms,
      80-620 microA, 5 min.) on mechanically evoked (brush and innocuous press on the
      hind paw) responses and spontaneous discharges were investigated in wide-dynamic
      range (WDR) neurons in three groups of animals: (1) rats that displayed
      'allodynia' after nerve ligation (2) rats without signs of 'allodynia' after
      surgery and (3) control, intact rats. A significantly increased frequency of
      spontaneous discharge and of responsiveness to brush and press was found in the
      group of allodynic, as compared with non-allodynic and control rats. The majority
      (63%) of the investigated neurons in these animals displayed afterdischarge in
      response to press stimulation. SCS induced a significant depression of both the
      principal response and the afterdischarge in allodynic rats: the discharge during
      brush stimulation was reduced to 86 +/- 8.2% and during press to 77.4 +/- 4.5% as
      compared with the prestimulation value. These depressive effects on evoked
      responses in allodynic rats outlasted SCS by 10.5 +/- 1.7 min during which time
      the responses gradually recovered. The frequency of spontaneous discharge was
      markedly decreased in approximately one third of the neurons, whereas in another
      third it was increased. In non-allodynic and control rats, SCS had no significant
      depressive effects on the evoked responses and spontaneous discharge. The results
      suggest that SCS may provide a suppressive action on dorsal horn neuronal
      hyperexcitability associated with signs of peripheral neuropathy. The suppressive
      effect of SCS on tactile allodynia, as previously observed in behavioral
      experiments, presumably corresponds to a normalization of the excitability of WDR
      cells in response to innocuous stimuli.

PMID- 10068169
TI  - Auditory evoked potentials and multiple personality measures in migraine and post
      traumatic headaches.
AB  - Migraine sufferers have abnormal cerebral information processing and personality
      disorders, post-traumatic headache sufferers also have some personality changes.
      We therefore, studied intensity dependence of auditory evoked potentials,
      Plutchik-van Praag's depression inventory, Zuckerman's sensation seeking scales
      and Zuckerman-Kuhlman's personality questionnaire in patients suffering from
      migraine without aura (n = 26) and chronic post-traumatic headaches (n = 26) as
      well as in healthy volunteers (n = 30). The migraine group showed significantly
      increased neuroticism-anxiety than controls, increased intensity dependence of N1
      P2, and decreased thrill and adventure score compared with the controls and post
      traumatic headaches. The post-traumatic headache had significantly increased
      depression compared with the controls, and increased disinhibition compared with
      the controls and migraines. This study demonstrates that the two headache types
      have different neurophysiological and personality traits. The pronounced
      intensity dependence of N1-P2 suggests a cortical potentiation response, together
      with a decreased thrill and adventure seeking, favor a lower serotonergic
      innervation in migraine. While the elevated disinhibition and depression, as
      consequences, may be linked with the wide cortical neuronal/axonal degeneration
      in post-traumatic headache.

PMID- 10068170
TI  - Actions of intrathecal diphtheria toxin-substance P fusion protein on models of
      persistent pain.
AB  - Substance P (SP) plays a central role in the transduction of second messenger
      signals from primary afferent nociceptive terminals to second-order neurons in
      the spinal cord. We have tested a recombinant engineered diphtheria toxin/SP
      fusion protein (DAB389SP) in acute and chronic pain models in the rat. DAB389SP
      binds to the SP receptor (SPR) and is internalized and kills SPR-expressing cells
      by blocking cellular protein synthesis. DAB389SP delivery was by intrathecal
      infusion, of varying duration, at the lumbar level. In the chronic constriction
      injury model of neuropathic pain a significant reduction in mechanically induced
      hyperalgesia was obtained. This effect was less marked in an acute carageenan
      inflammation model. Although other pain characteristics (mechano-allodynia, cold
      allodynia, and heat-hyperalgesia) showed some improvement, these were less
      pronounced. Immunocytochemistry revealed a toxin-induced reduction in lamina I,
      of SPR and of NMDA NR1 subunit receptor expressing neurons, and of c-Fos, an
      inducible molecular marker of persistent nociceptive activity. The use of
      cytotoxic fusion proteins to target specific cell types may be of considerable
      benefit in the study of nociception and the treatment of chronic pain.

PMID- 10068171
TI  - The kappa opioid agonist GR89,696 blocks hyperalgesia and allodynia in rat models
      of peripheral neuritis and neuropathy.
AB  - Previous work demonstrated that, in rats, intrathecal GR89696, a putative kappa-2
      opioid receptor agonist, inhibited hyperalgesia to noxious heat in an inflamed
      hind paw (anti-hyperalgesic effect). Non-inflamed paws were not influenced by
      kappa-2 receptor activation. The question addressed in this study was whether
      GR89696 was as effective in blocking hyperalgesia and allodynia in nerve injury
      models as it was in the inflammation model. GR89696 (6 nmoles, i.t.) completely
      reversed the hyperalgesia and allodynia observed in both the neuropathy and
      neuritis models in all sensory tests. However, it did not alter sensory function
      in non-injured limbs nor in sham operated animals. Naloxone (1 mg/kg, i.p.)
      reversed the anti-hyperalgesic and anti-allodynic effects of GR89696. The mu
      agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69593 (100 nmoles, i.t.)
      only partially reversed hyperalgesia and allodynia. These findings suggest that
      kappa-2 opioid receptors may be a useful target for the pharmacological control
      of hyperalgesia and allodynia.

PMID- 10068172
TI  - Effect of NGF and anti-NGF on neuropathic pain in rats following chronic
      constriction injury of the sciatic nerve.
AB  - The systemic administration of anti-nerve growth factor (NGF) antibodies can
      prevent local sensory hypersensitivity and block nociceptive fibers from
      sprouting into denervated adult rat skin. However, in the case of chronic
      constriction injury (CCI) in a rat, there is evidence that NGF reverses some
      effects of axotomy and alleviates thermal hyperalgesia. It is with this in mind
      that we investigated the influence of local anti-NGF and NGF on neuropathic pain
      and collateral sprouting caused by CCI. In our study, we looked at the effects to
      the ligated nerves after 30 consecutive days of local injections of anti-NGF and
      NGF. A high-dose of anti-NGF (1800 ng) was found to eradicate heat and cold
      hyperalgesia during postoperative days 16-28 and from days 8 to 34 after CCI,
      respectively. Our results show that a low-dose anti-NGF (18 ng) only mildly
      alleviates heat hyperalgesia but not cold hyperalgesia. There is evidence that a
      rebound phenomenon occurs for a short period of time after the anti-NGF
      injections cease. Results show that anti-NGF injections, whether in a high or low
      dose, significantly reduces the severity of autotomy or prevents the spread of
      collateral sprouting from the saphenous nerve into the sciatic innervation
      territory. In contrast, when a NGF (0.75 ng/g body weight) was applied to the
      ligated nerve immediately after the ligation, heat and cold hyperalgesia were
      eradicated during postoperative days 4-68 and from days 4 to 28, respectively.
      The results show that the effect of anti-NGF is delayed at the onset, is short in
      duration, and is dependent on the dosage. However, anti-NGF but not NGF blocked
      collateral sprouting and decreased the severity of autotomy, suggesting that anti
      NGF may be a better potential alternative analgesic for the treatment of
      neuropathic pain in humans. The different initiation times to abolish thermal
      hyperalgesia by anti-NGF (delayed onset) and NGF (early onset) suggests that
      alterations in neurotrophic factors contribute to the development of behavioral
      hyperalgesia via a complex mechanism in CCI rats.

PMID- 10068173
TI  - Relationship between the chronic pain grade and measures of physical, social and
      psychological well-being.
AB  - Chronic pain is an important cause of suffering, disability and loss of
      productivity within the community. Chronic pain can also be viewed as a
      multidimensional phenomenon, and may be associated with increased suffering of a
      social and psychological nature, as well as physical suffering. In this paper,
      the severity of the chronic pain gradings (CPG) is defined in terms of physical,
      social and psychological well-being, as measured by the SF36 and Glasgow Pain
      Questionnaire. Although previous work has shown the chronic pain grade to be a
      valid measure of chronic pain severity, little is known of the relationship
      between this and other health measures. A random sample of 5036 individuals,
      representative of the general population, stratified for age and sex, was drawn.
      A further sample of 4175 patients was drawn from a list of patients enrolled for
      repeat prescriptions for analgesic medication. A questionnaire survey was carried
      out, and response rates of 82 and 87% were achieved, respectively. The
      comparisons described confirm the widespread impact of chronic pain on all
      aspects of health, supporting the multidimensional view. These findings are
      important in addressing the management of chronic pain patients, and in
      particular, the social and psychological well-being of a patient needs to be
      addressed in parallel with the physical well-being in order to successfully
      reduce the suffering associated with chronic pain.

PMID- 10068174
TI  - Pharmacological studies on a rat model of trigeminal neuropathic pain: baclofen,
      but not carbamazepine, morphine or tricyclic antidepressants, attenuates the
      allodynia-like behaviour.
AB  - Trigeminal neuralgia is an example of an extreme form of neuropathic pain and
      continues to be a real therapeutic challenge. Although the pathophysiology of the
      disorder is uncertain, vascular compression of the trigeminal root resulting in
      damage to primary afferent neurons is thought to play a major role in the
      generation of pain. In the present study, we have used a recently developed rat
      model of trigeminal neuropathic pain, where the neuropathy is produced by a
      chronic constriction injury of the infraorbital branch of the trigeminal nerve
      (CCI-ION), and for the first time studied the effects of various pharmacological
      treatments on this purely sensory model of neuropathic pain. Rats with a CCI-ION
      consistently display a series of spontaneous behavioural abnormalities that may
      be indicative of trigeminal paraesthesias/dysesthesias. A hyper-responsiveness of
      the territory of the ligated infraorbital nerve to light mechanical stimulation
      with von Frey hairs also develops at 7-12 days after the injury. Pharmacological
      studies indicated that the mechanical hyper-responsiveness could be reversibly
      abolished by local injections of alphacaine into the close proximity of the
      injured nerve. The allodynia-like behaviour was resistant to i.v. morphine.
      Similarly, single and repeated injections (using the respective T 1/2 as an
      interval) of tricyclic antidepressants amitriptyline and clomipramine were devoid
      of effects on the mechanical allodynia-like behaviour. Carbamazepine was
      effective only after doses (> or =10 mg/kg s.c.) that already caused disturbances
      in motor co-ordination in the rotarod test. Repeated injections of baclofen (3
      mg/kg s.c.) partially alleviated the mechanical allodynia-like behaviour without
      effects on rotarod performance. The partial anti-allodynic effect of a single
      injection (5 mg/kg) of baclofen, which was already accompanied by slight motor
      disturbances, could be antagonized by CGP35348, a selective GABA(B)-receptor
      antagonist. Functional deficits in the GABAergic system may play an important
      role in the pathogenesis of this purely sensory rat model of trigeminal
      neuropathic pain.

PMID- 10068175
TI  - Validity of an illness severity measure for headache in a population sample of
      migraine sufferers.
AB  - The headache impact questionnaire (HImQ) is used to measure pain and activity
      limitations from headache over a 3-month recall period. In a prior study, the
      test-retest reliability of the eight-item HImQ score was found to be relatively
      high (0.86). In the current study, we examined the validity of the eight-item
      HImQ by comparing the overall score and individual items to equivalent measures
      from a 90-day diary. Pain and activity limitations due to headache were assessed
      in a population-based sample of 132 migraine headache sufferers enrolled in a 90
      day daily diary study who completed the HImQ at the end of the study. The HImQ
      score was derived from four frequency-based questions (i.e. number of headaches,
      missed days of work, missed days of chores, or missed days of non-work activity)
      and four summary measures of average experience across headaches (i.e. average
      pain intensity, and average reduced effectiveness when having a headache at work,
      during household chores, and in non-work activity). Diary based measures were
      used as the gold standard in evaluating the HImQ score. Mean and median values of
      frequency-based HImQ items (e.g. number of headaches) were similar to equivalent
      diary measures, indicating no systematic bias. In contrast, HImQ measures of
      average experience across attacks (e.g. average pain intensity) overestimated
      equivalent diary measures and, in general, better approximated diary measures for
      migraine headaches, rather than all headaches. The highest correlations between
      HImQ and diary items were observed for headache frequency and average pain
      intensity, the two general headache measures, followed by measures of reduced
      effectiveness. Among frequency-based measures, the strength of the correlation
      was directly related to the magnitude of the mean. The higher the mean value, the
      higher the correlation. The correlation between the HImQ score and diary based
      score was 0.49. The HImQ score is moderately valid. Frequency-based items (e.g.
      number of missed work days) were found to be unbiased and the highest correlation
      coefficients were observed for frequency-based items with relatively high mean
      counts (number of headaches, number of missed non-work days). These findings have
      implications for measuring severity of chronic episodic conditions like headache,
      asthma, back pain, arthritis, epilepsy, and panic disorder, which can cause
      limitations to activities. The validity of illness severity measures may be
      improved by using frequency-based questions to assess both missed activity days
      and days with significantly reduced effectiveness or productivity (e.g. by 50% or
      more). By combining the count for both missed days and days where productivity is
      substantially reduced, the mean of the frequency-based measure will be increased,
      a factor which may improve the overall validity of the item. A severity measure
      can be derived from such items by simple addition and provides a scale with
      intuitively meaningful units.

PMID- 10068176
TI  - Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain
      in cancer patients: a controlled dose titration study.
AB  - Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which
      the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that
      is dissolved in the mouth. It is undergoing investigation as a treatment for
      cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory
      flare of moderate to severe pain that interrupts otherwise controlled persistent
      pain. There have been no controlled trials of other treatments for this
      condition. To evaluate the safety and efficacy of ascending doses of OTFC, a
      novel controlled dose titration methodology was developed that applied blinding
      and randomization procedures to the evaluation of recurrent pains in the home
      environment. The study was a multicenter, randomized, double-blind dose titration
      study in ambulatory cancer patients. The sample comprised adult patients
      receiving a scheduled oral opioid regimen equivalent to 60-1000 mg oral morphine
      per day, who were experiencing at least one episode per day of breakthrough pain
      and had achieved at least partial relief of this pain by use of an oral opioid
      rescue dose. After collection of 2 days of baseline data concerning the efficacy
      of the usual rescue drug, patients were randomly treated with either 200 or 400
      microg OTFC unit doses in double-blind fashion. Up to two breakthrough pains each
      day could be treated with up to four OTFC unit doses per pain. OTFC in unit doses
      containing 200, 400, 600, 800, 1200 or 1600 microg of fentanyl citrate were
      available for the study. The unit dose was titrated upward in steps until the
      patient had 2 consecutive days on which breakthrough pain could be treated with
      the single unit dose, titration was ineffective at a 1600 microg unit dose, or 20
      days elapsed. To maintain the double-blind, orders to titrate up were ignored one
      third of the time according to a pre-defined randomization schedule accessible
      only to an unblinded study pharmacist. Main outcome measures included, numeric or
      categorical measures of pain intensity, pain relief, and global assessment of
      drug performance. Dose response relationships were found suggesting that the
      methodology was sensitive to opioid effects. Seventy-four percent of patients
      were successfully titrated. There was no relationship between the total daily
      dose of the fixed schedule opioid regimen and the dose of OTFC required to manage
      the breakthrough pain. Although the study was not designed to provide a
      definitive comparison between OTFC and the usual rescue drug, exploratory
      analyses found that OTFC provided significantly greater analgesic effect at 15,
      30 and 60 min, and a more rapid onset of effect, than the usual rescue drug.
      Adverse effects of the OTFC were typically opioid-related, specifically
      somnolence, nausea and dizziness. Very few adverse events were severe or serious.
      This study demonstrated the feasibility of controlled trial methodology in
      studies of breakthrough pain. OTFC appears to be a safe and effective therapy for
      breakthrough pain, and dose titration can usually identify a unit dose capable of
      providing adequate analgesia. If the lack of a relationship between the effective
      OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be
      needed in the clinical use of this formulation. Further investigation of OTFC as
      a specific treatment for breakthrough pain is warranted.

PMID- 10068177
TI  - A case of reflex sympathetic dystrophy (complex regional pain syndrome, type I)
      resolved by cerebral contusion.
AB  - We present a case of refractory reflex sympathetic dystrophy (RSD) (complex
      regional pain syndrome, type I) whose symptoms (ongoing pain, allodynia,
      hyperhydrosis and temperature abnormalities) were resolved after the patient
      suffered a traumatic cerebral contusion in the left temporal lobe, which caused
      no neurological deficit. This case suggests that symptoms of some RSD patients
      may largely sustained by a complex network involving the brain.

PMID- 10068178
TI  - Comments on Kingery, PAIN, 73 (1997) 123-139. Controlled randomized trials failed
      to demonstrate that sympathetic blocks (SB) are more effective than placebo for
      relieving complex regional pain syndromes (CRPS)

PMID- 10068179
TI  - Comments on Ohrbach and Dworkin, PAIN, 74 (1998) 315-326. Studies on factors
      predicting the long-term outcome of pain disorders and TMDs.

PMID- 10068180
TI  - Operative treatment of spondylodiscitis--what is the most effective approach?
AB  - In a study the results recorded in 34 surgically treated patients with specific
      or unspecific spondylodiscitis after dorsoventral one-stage instrumentation with
      CDI and anterior grafting (group 1) were compared with those obtained in a group
      of 38 patients treated with anterior CDH instrumentation in combination with
      anterior grafting (group 2). The mean observation periods were 48.4 (19-82)
      months in group 1 and 29.0 (8-54) months in group 2. In both groups the infection
      healed after fusion without a secondary operation. In group 1 the mean values for
      blood loss, operating time, length of hospital stay and fusion length (3.5
      segments) were significant higher than those in group 2; in particular, the
      fusion length was shorter (1.3 segments) in group 2. Only 8 patients in group 1
      were treated with postoperative external support. The mean preoperative segmental
      angle of 18.2 degrees (group 1) was corrected by a mean of 11.9 degrees, and the
      reposition loss during follow-up amounted to an average of 2.7 degrees. Group 2
      showed a mean preoperative segmental deformity angle of 13.4 degrees, which was
      corrected by 11.6 degrees, and the loss of reposition was 2.9 degrees on average.
      Even in florid spondylodiscitis a short-range anterior fusion of the affected
      spinal segment can be performed with a primary stable implant, avoiding a second
      operation without an increased risk of infection-related dislocation. In the
      authors' own experience a secondary dorsal operation can be avoided except in the
      case segment L-5/S-1, the fast mobilization without external support allows a up
      to-date treatment in this severe spinal disease.

PMID- 10068181
TI  - Asymptomatic or minimally symptomatic traumatic epidural haematomas: comparison
      of the results of surgical and conservative management related to SPECT and
      neuropsychological tests. Preliminary results.
AB  - One hundred and thirteen patients with asymptomatic or minimally symptomatic
      epidural heamatomas treated surgically or conservatively in our department were
      collected prospectively. Between 3 and 6 months after the head injury a SPECT
      (single photon emission computed tomography) study for evaluation of the three
      dimensional cerebral blood flow distribution and extensive neuropsychological
      tests were performed in 22 patients. The preliminary results of this prospective
      study have demonstrated that minimally symptomatic or asymptomatic EDHs cause no
      pathologic SPECT findings and that neuropsychological impairment and duration of
      the haematoma do not affect the results of conservative management.

PMID- 10068182
TI  - Transtracheal electrical stimulation of the spinal cord for intraoperative
      monitoring of the motor pathway.
AB  - Because of the suppressant effects of anesthetic drugs and muscle relaxants on
      motor responses elicited by either magnetic or electrical transcranial
      stimulation, intraoperative monitoring of the motor system, and especially
      monitoring of lower limb function, presents many difficulties. The upper part of
      the spinal cord was stimulated in 14 anesthetized and relaxed dogs with a cathode
      attached to the intratracheal tube and an anode fixed above the upper cervical
      spinous processes. Action potentials evoked by single and serial stimuli were
      recorded from the exposed right femoral nerve and quadriceps muscle Averaging was
      necessary for serial stimulations. Reproducible early and late responses to both
      single and serial stimulations were recorded during regular anesthesia. The
      origin of the different responses is discussed. Transtracheal stimulation of the
      spinal cord is easy to perform and the responses recorded from the peripheral
      nerve or limb muscle are well reproducible in regular anesthesia. The method
      seems to be appropriate for intraoperative monitoring of the thoracolumbar spine.

PMID- 10068183
TI  - Cytochemical and microbiological testing of CSF and catheter in patients with
      closed continuous drainage via a lumbar subarachnoid catheter for treatment or
      prevention of CSF fistula.
AB  - A study was performed to evaluate the efficacy of closed continuous drainage
      (CCD) via a lumbar subarachnoid catheter for prevention or treatment of CSF
      fistulas. In addition to the analysis of the physical, chemical and biological
      properties of the CSF obtained, the catheters themselves were tested on removal
      to identify any microorganisms contaminating them. Other factors taken into
      consideration were the symptoms reported by the patients during positioning of
      the catheter and while it was in place, any variations in body temperature and
      local inflammatory effects on the nerve roots of the cauda equine and surrounding
      tissues. The low percentage of systemic and local infections observed testifies
      to the safety of this method, regardless of the duration of treatment.

PMID- 10068184
TI  - Importance of cranial nerve involvement in nasopharyngeal carcinoma. A clinical
      study comprising 124 cases with special reference to clinical presentation and
      prognosis.
AB  - A review of nasopharyngeal carcinomas (NPCs) treated in the Hacettepe University
      Hospitals is presented. One hundred twenty-four patients between the ages of 3
      years and 72 years were managed in the period 1968-1992. Of these cases, 48 had
      only cranial nerve (CN) involvement on admission. The most commonly affected CNs
      were the VIth and the Vth, in that order. The prognostic significance of this
      finding is obvious, because early diagnosis and treatment is vital in a cancer
      patient. This study includes retrospective analysis of 124 patients with NPC. The
      patients were investigated with respect to clinical and radiological diagnosis
      and outcome. Our results also show that CN involvement in NPC usually requires
      careful neuro-otological examination. It is suggested that increased knowledge
      and understanding of the disease among neurosurgeons, neurologists and ENT
      surgeons would improve the prognosis of patients with NPC.

PMID- 10068185
TI  - Cranio-cerebral erosion: delayed diagnosis and treatment.
AB  - Cranio-cerebral erosion is a well-known complication of calvarian fracture with
      underlying dural tear and cerebral injury in infancy and early childhood. The
      anatomy, pathogenesis and natural evolution of these lesions remain obscure. The
      common clinical symptoms are seizures, focal neurological deficits, impairment of
      consciousness and a soft subgaleal mass. Three patients of cranio-cerebral
      erosion who underwent delayed surgery in their adult lives are presented to
      illustrate the common and uncommon features, and their long-term outcome is
      discussed.

PMID- 10068186
TI  - Complications of brain tissue pressure monitoring with a fiberoptic device.
AB  - Seventy-five patients with intracranial hypertension whose Glasgow Coma Score
      (GCS) was 8 or below and in whom intracranial pressure (ICP) was monitored were
      examined for complications of this procedure. In 20 of the 75 patients we used
      only an intraparenchymal fiberoptic ICP monitoring transducer, while, in the
      remaining 55 patients, who required CSF drainage, a ventricular drainage set
      (VDS) was used in addition to ICP monitoring. The duration of monitoring with the
      ICP transducer alone was approximately 5.1+/-2.6 das (min. 1, max. 13) and that
      of ICP monitoring with VDS was 6.2+/-3.1 days (min. 1, max. 13). In 8 cases a
      total of 9 complications were experienced (12%). These complications were
      infection in 3 cases (4%), epidural hematoma in 2 cases (2.7%), disconnection in
      2 cases (2.7%) and contusion in 2 cases (2.7%). Although none of the 44 patients
      who were monitored for less than 5 days experienced infection, 3 of the 31
      patients monitored for longer than 5 days did experience infection (9.7%)
      (p<0.05). None of the 20 patients who underwent ICP monitoring only experienced
      infection. However, 3 of the 55 patients in whom the ventricular drainage set was
      implanted in addition to the transducer for ICP monitoring experienced infection
      (p<0.05). Owing to its minimally invasive nature, low complication rate, and
      accuracy in monitoring the parenchyma pressure, the Camino fiberoptic
      intraparenchymal monitor has become the system of choice in our clinic.

PMID- 10068187
TI  - Effect of nimodipine and N-acetylcysteine on lipid peroxidation after
      experimental spinal cord injury.
AB  - The effectiveness of nimodipine and N-acetylcysteine in experimental spinal cord
      injury was evaluated by measuring tissue lipid peroxidation levels of the damaged
      spinal cords 1 hour after the injury We used the clip compression method to
      produce acute spinal cord injury in 40 female Sprague-Dawley rats were used. The
      rats were divided into four groups of 10 each. Lipid peroxidation was assessed by
      measuring the tissue content of malonil dialdehyde (MDA). In group 3, nimodipine,
      and in group 4, N-acetylcysteine, was administered i.p. as a single dose
      immediately after the injury. The rats were sacrificed 1 hour after clip
      application. The tissue mean MDA content was 3,992 micromol MDA/gww in group 1
      (sham operated), 10,192 micromol MDA/gww in group 2 (trauma), 10,449 micromol
      MDA/gww in group 3 (nimodipine treatment) and 9,009 micromol MDA/gww in group 4
      (N-acetylcysteine treatment). These results demonstrated that a single dose of
      nimodipine and N-acetylcysteine had no effect on peroxidation of lipid membranes
      in the early period of experimental spinal cord injury.

PMID- 10068188
TI  - Somatosensory spinal cord evoked potentials in the evaluation of the effect of
      dexamethasone in experimental spinal cord injury.
AB  - We studied the effects of high-dose dexamethasone on amplitude and latency values
      of spinal cord evoked potentials. Thirty-three rabbits were divided into three
      equal groups. The first group served as the control group, the others received
      high-dose (2.5 mg/kg) dexamenthasone, the second group 1 hour prior to and the
      third group immediately after the induction of a spinal cord trauma in segment
      T12. The spinal cord evoked potentials were recorded epidurally from T12 segment
      5 min before and 5, 30, 60, 90, 120 and 150 min after trauma. Pretreatment with
      dexamethasone (group II) prevented the latency delay, and later treatment with
      dexemethasone (group III) prevented the latency delay partially. Our results
      suggest that when dexamethasone is given prophylactically it prevents latency
      alteration, while treatment with dexamethasone after lesioning prevents latency
      alteration partially. From our results we conclude that pretreatment with
      dexamethasone may involve different mechanisms than were activated in the
      posttreatment group.

PMID- 10068189
TI  - Cavernous angioma of the VIIIth cranial nerve. A case report.
AB  - We report a case of a 24-year-old woman affected by a cavernous angioma of the
      right VIIIth cranial nerve associated with a venous angioma. The malformation was
      diagnosed by MRI, performed in relation to an acute onset of right anacusia. The
      case report is indicative that, even if unusual, an acute onset of an
      cerebellopontine angle syndrome can be subsequent to a bleeding cavernous
      angioma. This occurrence must be kept in mind in the differential diagnosis of
      the cerebellopontine angle tumors.

PMID- 10068190
TI  - Foramen magnum meningioma presenting as amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative disease of the
      nervous system. It affects adults in all age groups and leads to death few years
      after the diagnosis. The etiology is unknown, and there no convincing medical or
      surgical therapy Some diseases can mimic ALS. If diagnosed early these may be
      treatable, but if misdiagnosed as ALS and left untreated they may be fatal. We
      present a case of foramen magnum meningioma presenting clinically as ALS. After
      surgery, the symptoms disappeared and the neurological deficits improved.

PMID- 10068191
TI  - "Kissing" bilateral large carotid-ophthalmic aneurysms. A case report.
AB  - A case of unruptured bilateral large carotid-ophthalmic aneurysms, which appear
      to be adjoining and "kissing" each other when visualized by three-dimensional
      computed tomographic angiography (3-D CTA), is reported. Although bilateral
      carotid-ophthalmic aneurysms are not rare, bilateral large ones are quite rare,
      and direct imaging of "kissing aneurysms" of this portion has not been reported.
      Since 3-D CTA is becoming a useful tool for the diagnosis of cerebral aneurysms,
      we propose that these and similar bilateral large carotid-ophthalmic aneurysms
      are good candidates for the term "kissing aneurysms".

PMID- 10068192
TI  - A giant dissecting aneurysm mimicking serpentine aneurysm angiographically. Case
      report and review of the literature.
AB  - Intracranial dissecting and giant serpentine aneurysms are rare vascular
      anomalies. Their precise cause has not yet been completely clarified, and the
      radiological appearance of such lesions can be different in each case according
      to the effect of hemodynamic stress on a pathologic vessel wall. For berry
      aneurysms, available evidence overwhelmingly favors their causation by
      hemodynamically induced degenerative vascular disease and there is an obvious
      need to determine the hemodynamic parameters most likely to induce the precursor
      atrophic lesions. In this study, a case of a giant dissecting aneurysm
      angiographically mimicking serpentine aneurysm of the right ophthalmic artery is
      reported and the relevant literature is reviewed to investigate the pathological
      characteristics and pathogenesis of this lesion. In the present case,
      radiological investigation of the lesion suggested a serpentine aneurysm, but the
      diagnosis was corrected to dissecting aneurysm subsequent to the pathological
      examination of the resected aneurysm. A giant dissecting aneurysm
      angiographically mimicking serpentine aneurysm and developing as the result of a
      circumferential dissection located between the internal elastic lamina and media
      is of particular interest when the etiology of these aneurysms is considered. To
      our knowledge this is the first report on intracranial dissecting aneurysm
      mimicking serpentine aneurysm angiographically. Our case illustrates the
      importance of careful serial section studies for a better understanding of the
      vascular pathology underlying the processes involved in intracranial serpentine
      aneurysms. We conclude that serpentine, dissecting and berry aneurysms may all
      arise by way of similar pathophysiological mechanisms.

PMID- 10068193
TI  - Basilar bifurcation aneurysms associated with persistent primitive hypoglossal
      artery.
AB  - We report two cases of ruptured basilar bifurcation aneurysm associated with a
      persistent primitive hypoglossal artery. Angiograms revealed low-positioned
      aneurysms; in both cases bilateral vertebral arteries and posterior communicating
      arteries were hypoplastic or aplastic. Both aneurysms were successfully clipped
      via subtemporal transtentorial approach through the craniotomy ipsilateral to the
      side of the primitive hypoglossal artery. The ipsilateral craniotomy and exposure
      of the cervical carotid artery were helpful for obtaining the proximal control of
      the basilar artery needed to perform the clipping procedure with safety.

PMID- 10068194
TI  - Ectopic dural osteolytic meningiomas.
AB  - Intracranial meningiomas usually originate from the arachnoidal cells of the
      internal dural layer: meningiomas that originate from different sites are
      ectopic. The authors describe the case of a small meningioma adhering to the
      external dural layer without involvement of the internal layer, accompanied by
      osteolysis of the internal surface of the skull. A review of the literature on
      cranial ectopic meningiomas yielded only four cases described as originating from
      the external dural layer. Osteolysis of the skull was always present and was not
      found to have prognostic significance. The authors suggest that these four
      primary ectopic meningiomas originating from the external dural layer should be
      differentiated from intraosseous meningiomas of the skull.

PMID- 10068195
TI  - A large anomalous anterior choroidal artery associated with internal carotid
      artery-posterior communicating artery aneurysm. Case report.
AB  - A case of a large anomalous anterior choroidal artery (AchA) associated with
      internal carotid artery-posterior communicating artery aneurysm is reported. At
      surgery, the large anomalous AchA mimicked the PcomA. Therefore, we initially
      mistook the large anomalous AchA for the PcomA, and the ICA-PcomA aneurysm for
      the dorsal ICA aneurysm arising at a location of other than an arterial division.
      This is a rare case of an anomaly of the AchA with an associated aneurysm found
      at surgery. Anatomical and surgical considerations are made.

PMID- 10068196
TI  - How does metyrapone decrease seizures?

PMID- 10068197
TI  - Recent advances in bone biology provide insight into the pathogenesis of bone
      diseases.
AB  - Bone is modeled during embryonic development by endochondral and membranous
      ossification and is continuously remodeled thereafter under the influence of
      local and systemic factors to provide structural support and assist in calcium
      homeostasis. Recent studies of knockout and transgenic mice have increased
      understanding of the regulation of bone modeling during development and of
      remodeling of mature bone and have shed new light on the pathogenesis of a number
      of bone disorders. For example, fibroblast growth factor receptor-3, parathyroid
      hormone-related protein, and tartrate-resistant acid phosphatase affect the
      function of chondrocytes during endochondral ossification (the latter two by
      regulating their life spans and thus growth plate thickness and bone length).
      Some ubiquitously expressed genes seem unexpectedly to have unique functions that
      are largely confined to bone cells: M-CSF, C-Fos, PU.1, and NF-kappaB are
      required for osteoclast formation, whereas c-Src and Mitf (microphthalmia
      transcription factor) are required for osteoclast activity after the cells have
      formed. Knockout of these genes results in osteopetrosis, a disorder
      characterized by persistence in marrow cavities of unresorbed osteocartilaginous
      matrix and, as in some affected humans, by increased mortality. Some proteins
      seem to act as negative regulators of bone cell function, for example
      osteoprotegerin (a soluble TNF receptor) in osteoclasts; osteocalcin, bone
      sialoprotein, and 5-lipoxygenase in osteoblasts. Regulation of osteoclast life
      span may be an important mechanism by which estrogen and bisphosphonates prevent
      bone loss in conditions characterized by increased bone resorption, such as
      postmenopausal osteoporosis. The unique requirement of bone cells for certain
      gene products raises the possibility that these cells may have specific responses
      to inhibitory or stimulatory agents, and that signaling molecules in these
      response pathways could be specific targets for novel therapies to treat or
      prevent common bone diseases.

PMID- 10068198
TI  - The 1918 flu and other influenza pandemics: "over there" and back again.

PMID- 10068199
TI  - Atypical ductular proliferation and its inhibition by transforming growth factor
      beta1 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic
      alcoholic liver disease.
AB  - Many acute and chronic liver diseases are often associated with atypical ductular
      proliferation (ADP). These ADPs have gained increasing interest since a number of
      recent observations suggest that ADPs may represent progenies of the putative
      liver stem cell compartment. In this study, we show that feeding mice with 3,5
      diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in persistent proliferation
      of primitive ductules with poorly defined lumens. Similar to oval cell
      proliferation in other rodent models as well as in various human liver diseases,
      DDC-induced ADP originated from the portal tract, spread into the hepatic lobule,
      and was associated closely with appearance of hepatocytes harboring an antigen
      (A6), which normally is expressed in biliary epithelium. Furthermore, DDC
      treatment severely inhibited the regenerative capacity of mice after partial
      hepatectomy. The development of ADP was selectively blocked in DDC-fed TGF-beta1
      transgenic mice producing active TGF-beta1 in the liver and no accumulation of
      new hepatocytes expressing the A6 antigen was observed. Moreover, the
      transforming growth factor beta1 (TGF-beta1) transgenic mice did not survive
      beyond 3 weeks from starting the DDC-containing diet. The results suggest that
      persistent activation of the hepatic stem cell compartment is essential for liver
      regeneration in the DDC model and that active TGF-beta1 may negatively control
      activation of stem cells in the liver. These data further emphasize the relevance
      of the DDC model as an experimental tool for studying chronic liver diseases.

PMID- 10068200
TI  - Tracking recurrent quantitative genomic alterations in colorectal cancer: allelic
      losses in chromosome 4 correlate with tumor aggressiveness.
AB  - Allelic imbalances are common events in cancer cells. Quantitative alterations in
      specific chromosomal loci have been linked to activation (gain) or inactivation
      (loss) of genes with a proven impact on tumor cell biology. The aim of this study
      was to detect new chromosomal regions recurrently altered in colorectal
      tumorigenesis and with a potential effect on patient's outcome. We have analyzed
      a series of human colorectal tumor biopsy specimens by using the DNA
      fingerprinting technique arbitrarily primed PCR. This approach provided
      information on 95 different loci randomly selected and distributed through out
      the cell's genome. Eight sequences displayed recurrent alterations associated
      with diminished patient survival. Four of them (showing allelic losses) were
      located in chromosome 4, one sequence in chromosome 2, and one sequence in
      chromosome 17. The chromosomal origin of the two remaining sequences could not be
      determined. Fine mapping of chromosome 4 bands suggested that there are at least
      two regions in chromosome 4 (4p14-16 and 4q21-28) susceptible to containing tumor
      suppressor genes the loss of which may affect tumor aggressiveness.

PMID- 10068201
TI  - Genetic profile of the giant cell glioblastoma.
AB  - Giant cell glioblastoma is a rare glioblastoma variant characterized by the
      presence of large, bizarre, multinucleated giant cells. This glioblastoma subtype
      develops clinically de novo after a short clinical history and contains a high
      frequency of p53 mutations. In this study, we screened a series of 18 giant cell
      glioblastomas for additional genetic alterations. PCR-SSCP followed by DNA
      sequencing revealed PTEN mutations in 5 of 15 tumors (33%). Of these, two
      mutations were located in exon 5, two mutations in exon 6, and one mutation each
      in exons 1 and 9. Four mutations were point mutations and two mutations were
      deletions. One neoplasm contained two PTEN mutations (exons 5 and 6). None of the
      giant cell glioblastomas showed a homozygous deletion of PTEN orp16, or
      amplification of MDM2. Immunohistochemically, MDM2 overexpression was either not
      observed or detected in only a minor fraction of tumor cells. Differential PCR
      revealed EGFR amplification in only one of 17 tumors (6%). These results indicate
      that giant cell glioblastomas occupy a hybrid position, sharing with primary (de
      novo) glioblastomas a short clinical history, the absence of a less malignant
      precursor lesion and a 30% frequency of PTEN mutations. With secondary
      glioblastomas that develop through progression from low-grade astrocytomas, they
      have in common a younger patient age at manifestation and a high frequency (>70%)
      of p53 mutations.

PMID- 10068202
TI  - Expression of the human P2Y6 nucleotide receptor in normal placenta and
      gestational trophoblastic disease.
AB  - The P2Y family of purinergic receptors are members of the G-protein-coupled
      receptor superfamily. The P2Y6 subtype is expressed at particularly high levels
      in the placenta, suggesting that P2Y6 plays an important role in placental
      function. However, the cellular localization of P2Y6 within the placenta is
      unknown. This study examined the expression of P2Y6 in first-trimester and full
      term placental tissues, as well as examples of gestational trophoblastic disease,
      by Northern blot analysis and in situ hybridization. P2Y6 message was present at
      similar levels in first-trimester and full-term placenta, and in situ
      hybridization revealed that message was most abundant in the cytotrophoblast of
      the villi and chorionic plate at both gestational stages. The syncytiotrophoblast
      harbored lower levels of P2Y6 in first-trimester placenta, and by full-term, the
      syncytiotrophoblast only focally expressed P2Y6 transcripts. Neither the
      intermediate trophoblast nor nontrophoblastic elements of the placenta expressed
      P2Y6. Molar disease expressed P2Y6 in the villous trophoblast but not in the
      proliferative intermediate trophoblast, recapitulating the pattern of first
      trimester placenta. Neither choriocarcinoma nor the choriocarcinoma cell lines
      JEG-3 and JAr expressed P2Y6 transcript. These findings reveal that P2Y6 mRNA
      production is highly characteristic of the epithelial-like cytotrophoblast and
      syncytiotrophoblast, whereas expression is absent in the mesenchymal-like
      intermediate trophoblast. Thus, P2Y6 may play an important role in trophoblastic
      development, differentiation, and neoplasia.

PMID- 10068203
TI  - Human prostate-specific transglutaminase: a new prostatic marker with a unique
      distribution pattern.
AB  - Human prostate-specific transglutaminase (hTGp) is a cross-linking enzyme, the
      physiologic function of which has not been established unequivocally yet. To gain
      insight into its distribution, we raised antisera against hTGp. By using Western
      blotting analysis, we found that these antisera specifically recognize a 77-kDa
      protein in prostatic fluids, seminal plasmas, and prostatic tissues. The
      concentrations of hTGp in these fluids and tissues were found to be highly
      variable among individuals. Immunohistochemical examination of several formalin
      fixed paraffin-embedded human tissues revealed an exclusive expression in the
      prostate. The histologic localization and distribution of hTGp within the
      prostate was assessed by studying multiple sections from tumor-containing
      prostatectomy specimens and needle biopsies. hTGp expression was entirely
      restricted to luminal epithelial cells. No basal epithelial cells or stromal
      cells were stained. Within the prostate, large areas without any hTGp-positive
      cells were seen. Immunopositive cells were present either in a scattered pattern
      or concentrated in single or multiple glands in which all luminal epithelial
      cells expressed hTGp. The latter staining pattern occurred frequently, but not
      exclusively, in the peripheral zone, whereas scattered expression was most often
      observed in the transitional zone. Expression of the hTGp protein could
      occasionally be observed in high-grade prostatic intraepithelial neoplasia, but
      was not detected in prostate carcinoma cells. The expression pattern as observed
      for hTGp has not been found thus far for any other prostate-specific marker.

PMID- 10068204
TI  - Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction
      up-regulates placenta growth factor expression: molecular evidence for "placental
      hyperoxia" in intrauterine growth restriction.
AB  - Early placental development occurs in an environment of relative hypoxia. Hypoxia
      promotes angiogenesis and up-regulates vascular endothelial growth factor (VEGF)
      expression while it down-regulates placenta growth factor (PIGF) that possess 53%
      homology with VEGF. Morphological studies show poor placental vascular
      development and an increase in the mitotic index of cytotrophoblasts in
      intrauterine growth restriction (IUGR). We hypothesized that the reported
      relatively high oxygen level in the intervillous space in contact with IUGR
      placental villi will limit angiogenesis by changes in VEGF and PIGF expression
      and function. Western immunoblot analysis demonstrates a diametric expression of
      PIGF and VEGF proteins throughout pregnancy with PIGF levels increasing and VEGF
      levels decreasing, consistent with placental oxygenation. In IUGR placentae, the
      ratio of PIGF/GAPDH mRNA was increased by 2.3-fold (p < 0.03) and PIGF protein
      levels were also increased, (p < 0.05) as compared with gestationally-matched
      normal placentae. PIGF mRNA and protein were localized to the trophoblast bilayer
      and villous mesenchyme of the human placenta throughout gestation. In vitro
      studies demonstrated that increasing oxygen tension (hyperoxia) up-regulated PIGF
      protein in term placental villous explants, whereas hypoxic culture of a term
      trophoblast choriocarcinoma cell line (BeWo) down-regulated PIGF mRNA and protein
      and VEGFR-1 (Flt-1) autophosphorylation. The addition of PIGF-1 to a
      spontaneously transformed first trimester cytotrophoblast cell line stimulated
      DNA synthesis while PIGF-2 had little effect. VEGF and PIGF exert their
      biological actions by means of a common receptor VEGFR-1. In the first trimester
      trophoblast cells, PIGF-1 increased the association of phosphorylated
      extracellular signal-related kinase (ERK) with VEGFR-1 immunoprecipitates while
      both PIGF-1 and PIGF-2 also potentiated endogenous VEGF mediated association of
      phosphorylated extracellular related kinase (ERK) with VEGFR-2 (KDR). More
      importantly, the addition of PIGF-1 had little effect while PIGF-2 inhibited cell
      growth in cultured endothelial cells derived from human umbilical vein. Nitric
      oxide (NO) is reported to promote angiogenesis and PIGF-2 inhibited the basal
      release of NO from the first trimester trophoblast. The tissue expression and
      functional studies support the hypothesis of "placental hyperoxia" in early-onset
      IUGR because hypoxia down-regulates trophoblast PIGF levels, PIGF expression is
      increased in IUGR, and PIGF-2 inhibits endothelial cell growth. Taken together,
      these changes provide a cellular explanation for the observed poor angiogenesis
      in the pathogenesis of IUGR and show that the two PIGF isoforms may modulate
      trophoblast and endothelial cell function differently, possibly through
      potentiation of VEGF mediated activation of VEGF-2.

PMID- 10068205
TI  - Growth factor expression in the obstructed developing and mature rat kidney.
AB  - The purpose of this study is to evaluate the role of keratinocyte growth factor
      (KGF), transforming growth factor-alpha (TGF-alpha), and their receptors in
      altered renal growth caused by complete ureteral obstruction in the developing
      kidney. Neonatal and adult rats underwent complete unilateral ureteral ligation
      or sham operation. The kidneys were harvested at 1, 5, 10, 20, and 30 days after
      obstruction. Renal growth and development was assessed by histology and
      immunohistocytochemical localization of vimentin, cytokeratin and smooth muscle
      alpha actin. Cellular proliferation was measured by [3H]thymidine labeling index
      of all cells. RNase protection assays were used to quantify mRNA encoding for
      KGF, KGF receptor, TGF-alpha, and epidermal growth factor (EGF) receptor.
      Ureteral obstruction in the developing kidneys resulted in decreased DNA
      synthesis, rapid parenchymal loss, myofibroblast proliferation in the
      interstitium, decreased tubular epithelial cells formation, and development of
      cystic dysplasia. In comparison, obstruction in the mature kidneys resulted in
      transient growth in the medullary ductal cells, parenchymal loss, and
      myofibroblast proliferation at a later time, lymphocytic infiltration in the
      interstitium but not cystic dysplasia. KGF and KGF receptor mRNA levels were
      increased in obstructed neonatal kidneys. Similarly, TGF-alpha and EGF receptor
      mRNA levels were increased. Delayed and more moderate increases in KGF, KGF
      receptor, and TGF-alpha expression were also seen in the obstructed mature
      kidneys. Of importance, the amount of EGF receptor mRNA was not increased in the
      obstructed compared with the contralateral or sham-operated adult kidneys. This
      study suggests that obstruction alters the normal expression pattern of KGF, TGF
      alpha, and their receptors in renal development. These changes may be responsible
      for the impaired renal growth and altered development seen in ureteral
      obstruction of the kidneys. Although some changes are similar to those seen in
      the adult kidney, the increased expression of TGF-alpha and cystic dysplasia are
      unique to neonatal obstruction.

PMID- 10068206
TI  - Changes in the pattern of fibronectin mRNA alternative splicing in acute
      experimental mesangioproliferative nephritis.
AB  - Fibronectins (FN) regulate cell migration, proliferation, and matrix formation
      during tissue injury. In humans, up to 20 different FN isoforms are generated by
      alternative splicing in three regions called EIIIA, EIIIB, and V, which have been
      implicated in the process undergoing wound healing and embryonic development.
      Specifically, EIIIA- and EIIIB-containing isoforms have been implicated in the
      regulation of cell proliferation and migration, whereas FN isoforms containing
      the full-length V region (named V120) are ligands to the VLA-4 integrin. To study
      the changes in the expression of FN isoforms in the anti-Thy-1 nephritis, an
      acute and self-resolutive model of mesangioproliferative nephritis, we analyzed
      the FN splicing patterns by means of ribonuclease protection assays. At Day 7
      after anti-Thy-1 monoclonal injection, time of the maximal matrix expansion and
      glomerular hypercellularity, EIIIA+, EIIIB-, and V120 FN mRNA isoforms were
      increased. In accordance with the mRNA studies, FN proteins, including the EIIIA
      and V120 regions, increased in the mesangium of nephritic rats, as assayed by
      immunohistochemistry. Coinciding with the EIIIA and V120 isoforms up-regulation,
      there was an increase in mesangial cell proliferation and in the number of VLA-4+
      infiltrating cells. At Day 14, in parallel with a remission of the above
      mentioned changes, there was a decline in the mRNA and protein FN isoforms
      increased in the previous phase. The marked and reversible changes in the pattern
      of FN isoforms and their temporal association with other indicators of glomerular
      injury suggest that certain FN isotypes are important and coordinated components
      of the mechanisms attempting to reverse glomerular damage.

PMID- 10068207
TI  - Prevention of myocardial reperfusion injury in rats by an antibody against
      monocyte chemotactic and activating factor/monocyte chemoattractant protein-1.
AB  - MCAF (monocyte chemotactic and activating factor)/MCP-1 (monocyte chemoattractant
      protein-1) is an important mediator of monocyte recruitment to inflammatory
      sites. However, its pathophysiologic role in myocardial reperfusion injury
      remains unknown. Male Wistar rats were anesthetized, and the left anterior
      descending coronary artery was ligated for an hour, after which the ligature was
      released. Northern blotting analysis revealed that MCAF/MCP-1 mRNA expression
      increased 16-fold in the reperfused region at 12 hours after reperfusion.
      MCAF/MCP-1 concentration in plasma and the heart was already elevated after hour
      of ischemia in this model. Goat polyclonal antibodies were prepared by repeated
      immunization of animals with purified, recombinant rat MCAF/MCP-1, and the
      neutralizing activities of this antibody were confirmed by monocyte chemotaxis
      assay and administration to rats with crescentic glomerulonephritis. Intravenous
      injection of anti-MCAF/MCP-1 antibody significantly reduced the infarct size at
      24 hours after reperfusion compared with the injection of control IgG (33.9 +/-
      5.1% vs 49.4 +/- 2.7% of ischemic area, mean +/- SEM). Administration of this
      antibody markedly decreased the intercellular adhesion molecule-1 mRNA expression
      and infiltration of macrophages, which suggested the pathophysiologic role of
      MCAF/MCP-1. Neutralization of MCAF/MCP-1 is beneficial by preventing reperfusion
      injury in a rat model of myocardial ischemia and reperfusion.

PMID- 10068208
TI  - Immunophenotypic diagnosis of acute leukemia by using decision tree induction.
AB  - We describe a model for decision making for bone marrow immunophenotypic analysis
      of acute leukemia. In this study, we used decision tree induction as an
      information processing system for the analysis of flow cytometry immunophenotype
      results of bone marrow specimens obtained for the diagnosis of acute leukemia. By
      using decision tree analysis, we queried which antibodies and at what percentage
      cut-offs led to particular diagnoses. Flow cytometry results of up to 27
      monoclonal antibodies from bone marrow specimens of 175 adult and pediatric cases
      were used: acute lymphoblastic leukemia (n = 80), myeloid leukemia (n = 44),
      mixed lineage (n = 16), and reactive marrow (n = 35). The percentage of positive
      cells was used as input data, and the diagnoses were used as output of the
      information processing system. Results of the decision tree showed an easy,
      accurate, and intuitive algorithm that can delineate a hierarchy of antibodies
      relevant to diagnosis. A correct discrimination of acute myeloid and lymphoid
      leukemia from benign bone marrow can be inferred by using the results of four to
      eight from a panel of up to 27 antibodies with an accuracy of 95%. Here, we
      describe a computer-aided model that uses decision tree induction applied to flow
      cytometry immunophenotype data. If generalizable, this technique may be an
      alternative approach to modeling complex information like that seen in
      hematopathology and may complement the immunologist's interpretation, along with
      cytochemistry and morphology results, in the diagnosis of acute leukemia.

PMID- 10068209
TI  - Direct actions of angiopoietin-1 on human endothelium: evidence for network
      stabilization, cell survival, and interaction with other angiogenic growth
      factors.
AB  - Angiopoietin-1 (Ang-1) is a recently described angiogenic protein that activates
      the endothelial Tie 2 receptor. Disruption of the Ang-1 gene shows that it has an
      indispensable role in blood vessel development, but it is not clear what specific
      effects, if any, Ang-1 has on endothelial cell (EC) phenotypes. Here, we show
      that Ang-1 dose-dependently stabilizes HUVEC network organization for up to 48
      hours; this action of Ang-1 is dependent on Tie-2 receptor activation, because a
      soluble form of the Tie2-, but not the Tie1-receptor, completely blocks the
      effects of Ang-1. Moreover, we show that Ang-1 potentiates the actions of other
      angiogenic growth factors. Ang-1 markedly increases the survival of vascular
      networks (up to 96 hours) exposed to either vascular endothelial growth factor or
      endothelial cell growth supplement, a form of acidic fibroblast growth factor. In
      addition, Ang-1 prevents apoptotic death in HUVEC triggered by withdrawal of
      endothelial cell growth supplement. Collectively, these data are consistent with
      the idea that Ang-1 directly acts on human EC and interacts with other angiogenic
      molecules to stabilize vascular structures by promoting the survival of
      differentiated ECs.

PMID- 10068210
TI  - Transgenic TIMP-1 inhibits simian virus 40 T antigen-induced hepatocarcinogenesis
      by impairment of hepatocellular proliferation and tumor angiogenesis.
AB  - Tissue inhibitors of metalloproteinases (TIMP) block proteolytic degradation of
      extracellular matrix and consequently impede tumor invasion and metastasis. In
      addition, we have previously reported that hepatic TIMP-1 modulation alters the
      susceptibility of the liver to oncogene (simian virus 40 T-antigen; TAg)-induced
      tumorigenesis in a double-transgenic mouse model. To identify the cellular
      processes by which TIMP-1 inhibits hepatocarcinogenesis, we examined the effects
      of TIMP-1 on four specific events that are important during tumorigenesis:
      hepatocellular proliferation, apoptosis, the stromal characteristics of the
      liver, and tumor vascularization. Transgenic mice with elevated or reduced
      hepatic TIMP-1 expression were bred independently with TAg transgenics. Liver
      tissue from littermates were analyzed by in situ hybridization with TIMP-1 cDNA
      probes; gelatin enzymography; immunohistochemistry for proliferating cell nuclear
      antigen, von Willebrand factor, and collagen type IV; reticulin histochemistry;
      and collagens type III and IV, laminin, fibronectin, and CD31 immunoblotting. We
      demonstrate that TIMP-1 overexpression significantly inhibited the proliferation
      of hepatocytes in TAg mice but did not affect their apoptotic index, the hepatic
      parenchymal architecture, or extracellular matrix composition, including
      collagens type III and IV, laminin, and fibronectin. Moreover, the hepatocellular
      carcinomas formed in TIMP-1-overexpressing mice had significantly reduced tumor
      vascularization; conversely, tumor vascularization was significantly increased in
      TIMP-1-reduced livers. These data indicate that TIMP-1 inhibits TAg-induced
      hepatocarcinogenesis by altering hepatocellular proliferation and tumor
      vascularization, without any effect on hepatocyte apoptosis and stromal
      composition. To our knowledge, this is the first in vivo demonstration that
      genetic modulation of TIMP-1 inhibits cellular proliferation and angiogenesis
      during hepatocarcinogenesis. This potentially extends the use of matrix
      metalloproteinase inhibitors in cancer beyond control of invasion and metastasis.

PMID- 10068211
TI  - Detailed in vivo analysis of interferon-gamma induced major histocompatibility
      complex expression in the the central nervous system: astrocytes fail to express
      major histocompatibility complex class I and II molecules.
AB  - To recognize and respond immunologically to foreign antigens, T lymphocytes
      require the presentation of foreign peptides by MHC molecules. To determine which
      cells of the central nervous system (CNS) are capable of expressing MHC
      molecules, we used confocal microscopy and dual immunofluorescence with cell
      specific and MHC-specific antibodies to study brain sections of adult mice. We
      took advantage of transgenic mice that initiate CNS-specific expression of IFN
      gamma at 8 weeks of age. This inflammatory cytokine is a strong inducer of MHC
      expression both in culture and in vivo. From this analysis, we clearly found MHC
      class I and II expression on endothelial, microglial, and oligodendrocyte cell
      types, but did not find astrocytes or neurons capable of expressing either MHC
      class I or II molecules under these conditions. This finding suggests that,
      although microglia and oligodendrocytes may participate in the antigen
      presentation process in the organism, we found no in vivo evidence to support the
      concept that astrocytes act as antigen-presenting cells.

PMID- 10068212
TI  - Expression of vascular endothelial growth factor receptor-3 and podoplanin
      suggests a lymphatic endothelial cell origin of Kaposi's sarcoma tumor cells.
AB  - Despite intensive research over the past decade, the exact lineage relationship
      of Kaposi's sarcoma (KS) tumor cells has not yet been settled. In the present
      study, we investigated the expression of two markers for lymphatic endothelial
      cells (EC), ie, vascular endothelial growth factor receptor-3 (VEGFR-3) and
      podoplanin, in AIDS and classic KS. Both markers were strongly expressed by cells
      lining irregular vascular spaces in early KS lesions and by tumor cells in
      advanced KS. Double-staining experiments by confocal laser microscopy established
      that VEGFR-3-positive and podoplanin-positive cell populations were identical and
      uniformly expressed CD31. By contrast, these cells were negative for CD45, CD68,
      and PAL-E, excluding their hemopoietic and blood vessel endothelial cell nature.
      Podoplanin expression in primary KS tumor lysates was confirmed by Western blot
      analysis. Both splice variants of VEGFR-3 were found in KS-tumor-derived RNA by
      RT-PCR. In contrast to KS tumor cells in situ, no expression of VEGFR-3 and
      podoplanin was detected in any of four KS-derived spindle cell cultures and in
      one KS-derived autonomously growing cell line (KS Y-1). Our findings that KS
      tumor cells express two lymphatic EC markers in situ strongly suggest that they
      are related to or even derived from the lymphatic EC lineage. Lack of these
      antigens on cultured cells derived from KS lesions indicates that they might not
      represent tumor cells that grow in tissue culture, but rather other cell types
      present in KS lesions.

PMID- 10068213
TI  - Biocatalytic nerve agent detoxification in fire fighting foams.
AB  - Current events across the globe necessitate rapid technological advances to
      combat the epidemic of nerve agent chemical weapons. Biocatalysis has emerged as
      a viable tool in the detoxification of organophosphorus neurotoxins, such as the
      chemical weapons VX and sarin. Efficient detoxification of contaminated
      equipment, machinery, and soils are of principal concern. This study describes
      the incorporation of a biocatalyst (organophosphorus hydrolase, E.C. 3.1.8.1)
      into conventional formulations of fire fighting foam. The capacity of fire
      fighting foams to decrease volatilization of contained contaminants, increase
      surface wettability, and control the rate of enzyme delivery to large areas makes
      them useful vehicles for enzyme application at surfaces. The performance of
      enzyme containing foams has been shown to be not only reproducible but also
      predictable. An empirical model provides reasonable estimations for the amounts
      of achievable surface decontamination as a function of the important parameters
      of the system. Theoretical modeling illustrates that the enzyme-containing foam
      is capable of extracting agent from the surface and is catalytically active at
      the foam-surface interface and throughout the foam itself. Biocatalytic foam has
      proven to be an effective, "environmentally friendly" means of surface and soil
      decontamination.

PMID- 10068215
TI  - Proceedings of the International Conference on Environmental Epidemiology and
      Exposure Analysis. Cuernavaca, Mexico, 26-29 August 1992.

PMID- 10068214
TI  - Editorial overview: motor control from molecules to bedside.

PMID- 10068216
TI  - Suboptimal ward care of critically ill patients. Assessment of quality of care
      was flawed.

PMID- 10068217
TI  - Suboptimal ward care of critically ill patients. Active management should prevent
      cardiopulmonary arrests.

PMID- 10068218
TI  - Suboptimal ward care of critically ill patients. Doctors don't review patients
      that nurses identify as highly dependent.

PMID- 10068219
TI  - Suboptimal ward care of critically ill patients. Inadequate staffing means
      problems are missed.

PMID- 10068220
TI  - Suboptimal ward care of critically ill patients. Checklist may help improve
      referral.

PMID- 10068221
TI  - Suboptimal ward care of critically ill patients. Medical training should focus on
      basic skills.

PMID- 10068222
TI  - Suboptimal ward care of critically ill patients. More intensive care beds are
      needed.

PMID- 10068223
TI  - Suboptimal care should have been defined. Course is available for surgical
      trainees.

PMID- 10068224
TI  - Suboptimal ward care of critically ill patients. Medical emergency teams improve
      care.

PMID- 10068225
TI  - Infantile spasms and vigabatrin. Visual field defects may be permanent.

PMID- 10068226
TI  - Treatment of gastro-oesophageal reflux disease in adults. "Step down" strategy of
      treatment would be expensive.

PMID- 10068227
TI  - Communicating with patients. Hostility can be a barrier to effective
      communication.

PMID- 10068228
TI  - Elective caesarean section on request. All types of anaesthesia carry risks.

PMID- 10068229
TI  - Elective caesarean section on request. Obstetricians are more than technicians.

PMID- 10068230
TI  - Elective caesarean section on request. Safest option is still to aim for vaginal
      delivery.

PMID- 10068231
TI  - Elective caesarean section on request. Unnecessary caesarean sections should be
      avoided.

PMID- 10068232
TI  - Elective caesarean section on request. Maternal age is important.

PMID- 10068233
TI  - Elective caesarean section on request. Pregnant women should have choices.

PMID- 10068234
TI  - Acute obstructive hydrocephalus complicating bacterial meningitis. Use of
      dexamethasone remains contentious.

PMID- 10068235
TI  - Acute obstructive hydrocephalus complicating bacterial meningitis. Hydrocephalus
      was probably non-obstructive.

PMID- 10068236
TI  - Acute obstructive hydrocephalus complicating bacterial meningitis. Neuroimaging
      has limitations.

PMID- 10068237
TI  - 50 years of the NHS. Demand must be reduced or funding must be increased.

PMID- 10068238
TI  - 50 years of the NHS. Picture painted of health service in Singapore was too rosy.

PMID- 10068239
TI  - Risk of breast cancer among female airline cabin attendants. Large European
      studies are now carried.

PMID- 10068240
TI  - Bournewood: an indefensible gap in mental health law. Law is inappropriate for
      patients admitted informally but who lack capacity.

PMID- 10068241
TI  - Laparoscopic versus open mesh repair of inguinal hernia. Recurrence rate is true
      test of hernia repair.

PMID- 10068242
TI  - Laparoscopic versus open mesh repair of inguinal hernia. Laparoscopic repair is
      good when undertaken by experienced surgeons.

PMID- 10068243
TI  - Laparoscopic verses open mesh repair of inguinal hernia. Costs and outcomes
      should always be presented in disaggregated form.

PMID- 10068244
TI  - Laparoscopic versus open mesh repair of inguinal hernia. Laparoscopic repair can
      be made less expensive.

PMID- 10068245
TI  - Laparoscopic versus open mesh repair of inguinal hernia. Unblinded trails may not
      be more reliable than observational studies.

PMID- 10068246
TI  - Identification of patients with atrial fibrillation in general practice. "While
      we're there" research disguises need for screening studies.

PMID- 10068247
TI  - Laparoscopic verses open mesh repair of inguinal hernia. Laparoscopic repair is
      much more expensive.

PMID- 10068248
TI  - A national target for reducing suicide. People over 65 should be a target group.

PMID- 10068249
TI  - Quality of care before admission to intensive care. Strategies for suboptimal
      care need evaluation.

PMID- 10068250
TI  - [Primary vesicoureteric reflux in children and adults. Proceedings of the 1998
      Congress of the French Association of Urology].

PMID- 10068251
TI  - Vital status ascertainment through the files of the Department of Veterans
      Affairs and the Social Security Administration.
AB  - Veterans of US military service are a valuable resource for epidemiologic
      studies, and the Department of Veterans Affairs (VA) files provide an effective
      way to gather mortality information on veterans, so long as these files provide
      reasonably complete death reporting. To determine the completeness of VA death
      reporting, we assembled an independent sample of known veteran deaths among males
      born between 1936 and 1955 and assessed the performance of VA death reporting in
      this sample. We also compared VA death ascertainment to Social Security
      Administration (SSA) ascertainment. Based on the more than 4300 deaths in our
      study, we found VA death reporting to be approximately 90% complete by itself and
      96% complete when used in conjunction with SSA death reporting. In addition, we
      found no evidence that VA death reporting changed substantially after passage of
      the Omnibus Budget Reconciliation Act of 1981, which limited eligibility for VA
      death benefits. Because veterans make up a large segment of the US population,
      our findings have particular relevance for studies in which mortality is a
      primary end point.

PMID- 10068252
TI  - Mechanisms of inflammation: symposium of the Sonderforschungsbereich (SFB 244),
      Hannover, Germany, 4-5 June 1998.

PMID- 10068253
TI  - Specificity of the 34-kilodalton immunodominant protein of Mycobacterium avium
      sp. paratuberculosis.

PMID- 10068254
TI  - [Current status and problems associated with antinuclear antibody analysis by
      indirect fluorescent antibody method].

PMID- 10068255
TI  - Amgen redux: ICOS Corporation.

PMID- 10068256
TI  - [Molecular biology of viral cardiopathies].

PMID- 10068258
TI  - Rosacea--a condition that needs special care.

PMID- 10068257
TI  - 14-3-3 protein, neuron-specific enolase, and S-100 protein in cerebrospinal fluid
      of patients with Creutzfeldt-Jakob disease.
AB  - We explored simultaneously 14-3-3 protein, neuron-specific enolase (NSE), and one
      astroglial protein, S-100, recently proposed as Creutzfeld-Jakob disease (CJD)
      markers, in the cerebrospinal fluid (CSF) of 129 patients with suspected CJD.
      Cutoff values for NSE and S-100 were established at 25 and 2.5 ng/ml,
      respectively. The highest sensitivity was observed for S-100 (94.2%) followed by
      14-3-3 (89.8%) and NSE (79.7%), while the highest specificity in CJD diagnosis
      was obtained with 14-3-3 protein (100%) as compared with NSE (91.5%) and S-100
      (85.4%). No influence of sex, genotype at codon 129 of the prion protein gene,
      time between sampling, and death or disease duration has been found. Based on 90
      cases initially referred as 'probable' or 'possible' CJD, with 14-3-3, NSE, or S
      100 we could correctly discriminate between 'CJD' or 'non-CJD' categories in
      94.4, 86.5, and 90% of the cases, respectively. When limited to 'possible CJD'
      cases, diagnosis based on one of the three CSF proteins was accurate in 98, 90.7
      and 87.3%, respectively. In view of the fact that the CSF 14-3-3 protein test
      alone has the highest specificity and good sensitivity, it appears that there is
      no additional advantage at the moment to include NSE and/or S-100 protein in the
      exploration of clinically suspected CJD cases.

PMID- 10068259
TI  - The risk of intracerebral haemorrhage with smoking. The Melbourne Risk Factor
      Study Group.
AB  - To determine whether smoking contributes to the risk of primary intracerebral
      haemorrhage (ICH) a case-control study was carried out on 331 consecutive cases
      of first-episode ICH as verified by computed tomography. Patients were age- and
      sex-matched to 331 community-based controls. Unlike other forms of stroke where
      smoking is an established risk factor, there was no increase in risk of ICH with
      smoking in this study (odds ratio, OR, 1.07, 95% confidence interval, CI,
      0.631.81). Similar ratios were obtained for past and current smokers. Neither the
      amount smoked nor the duration of smoking were associated with ICH. Further
      investigation, however, revealed an interaction between smoking and hypertension
      on the risk of ICH that was similar regardless of the amount of cigarettes
      currently smoked and was largely seen to be a phenomenon in men (OR 8.13, 95% CI
      2.0432.42). This interaction is a new finding, but the post-hoc nature of this
      analysis requires that it be further tested, preferably in a large prospective
      study.

PMID- 10068260
TI  - Seeking Haydn's secrets.

PMID- 10068261
TI  - Foundations of Clinical Cancer Research: Perspective for the 21st Century.
      Proceedings of a symposium honoring Dr. Emil J Freireich. Houston, Texas, March
      14-15, 1997.

PMID- 10068262
TI  - Advances in therapy of multiple myeloma: lessons from acute leukemia.
AB  - This paper traces the lack of progress, until recently, in the treatment of
      multiple myeloma (MM) to having ignored the principles that led to cure in acute
      leukemia more than 2 decades ago. Only in the mid-1980s did investigation begin
      to consider complete remission (CR) a research objective, representing a
      necessary first step toward cure. The experience with autologous and allogeneic
      stem cell-supported high-dose therapy is reviewed, demonstrating, in both
      historically controlled and randomized studies, the validity of the dose-response
      concept in MM in terms of increased CR rates as well as extended event-free (EFS)
      and overall survival (OS). Avoidance of hematopoietic stem cell-damaging agents,
      especially melphalan, nitrosoureas, and ionizing radiation to marrow-containing
      sites, assures the ability of peripheral stem cell collection of high quality and
      quantity, providing rapid engraftment so that mortality is well under 5%
      following high-dose melphalan (200 mg/m2). This treatment can be applied safely
      to patients even >70 years of age and in the presence of renal failure. Tandem
      autotransplants after multiregimen induction have yielded CR rates in the 40%
      range with median durations of EFS and OS of 43 and 62 months, respectively.
      Certain chromosomal abnormalities (11 and 13; and translocations) represent the
      dominant adverse prognosticator for EFS and OS, confirmed in over 500 patients
      including those with prior therapy. Allogeneic transplants, possible in less than
      10% of MM patients, are associated with a 50% mortality during the first year
      and, unfortunately, late relapses; thus, this approach should be reserved for
      patients with high-risk disease early in their management. A risk-based treatment
      algorithm that matches a patient's disease risk with the risk of intervention is
      presently used, followed by bisphosphonate therapy, not only to delay the onset
      of MM-related bone disease but also to induce tumor cell apoptosis, indirectly or
      directly, by down-regulation of cytokines with antiapoptotic activities. Although
      many patients relapse, this author subscribes to his mentor's motto: "Be Prepared
      for Success!".

PMID- 10068263
TI  - Drug development in solid tumors: personal perspective of Dr. Emil J Freireich's
      contributions.
AB  - The development of chemotherapy for patients with the major cancers progressed
      from the initial success attained in the treatment of acute leukemias and
      choriocarcinoma. Many of the principles of therapy were based on the concepts
      developed in the experimental laboratories and early clinical studies done at the
      NIH Clinical Center and other centers around the country. The purpose of this
      review is to describe some of the early advances in cancer therapy and show how
      many are based on the efforts of Dr. Emil J Freireich. Over his career, Dr.
      Freireich has published more than 500 papers and worked on more than 70 different
      drugs and combinations. The principles defined by Dr. Freireich, namely, the use
      of intermittent intensive chemotherapy to induce complete remissions (CRs),
      intensification of therapy in remission, and the use of unmaintained remissions
      to assess cure, have been important in developing curative chemotherapy programs
      in patients with acute leukemias. These same principles were applied to
      combination therapy of Hodgkin's disease as the nitrogen mustard, vincristine,
      procarbazine, and prednisone combination was developed. This led to the high CR
      and cure rate for this disease. The treatment of metastatic breast cancer does
      not produce a high proportion of CRs, and cures of metastatic disease are
      unlikely with chemotherapy alone. But adjuvant chemotherapy after surgery has
      resulted in a significant reduction in cancer mortality. Many challenges remain
      in increasing the cure rate for the major solid tumors. New avenues of
      controlling cell growth and metastases need to be explored. One approach that is
      exploitable is the use of drugs or nutrients to prevent cancer. Laboratory
      approaches are now becoming a clinical reality.

PMID- 10068264
TI  - Advances in the biological therapy and gene therapy of malignant disease.
AB  - Biological and gene therapy of cancer have become important components of
      clinical cancer research. Advances in this area are based on evidence for the
      presence of tumor antigens, antitumor immune responses, evasion of host control
      by tumors, and the recognition of host defense failure in cancer patients. These
      mechanisms are being corrected or exploited in the development of biological and
      gene therapy. Over the last decade, 9 biological therapies have received Food and
      Drug Administration approval, and another 12 appear promising and will likely be
      approved in the next few years. Our approach to gene therapy has been to
      allogenize tumors by the direct intratumoral injection of HLA-B7/beta2
      microglobulin genes as plasmid DNA in a cationic lipid into patients with
      malignant melanoma. In four Phase I studies, we found a 36% response by the local
      injected tumor and a 19% systemic antitumor response. In other cancers, gene
      transfer, expression, and an intratumoral T-cell response were seen, but no
      clinical response was seen. A variety of follow-up studies with HLA-B7 and other
      genes are planned. Evasion of host control is now a major target of gene therapy.
      Strategies to overcome this include up-regulation of MHC and introduction of cell
      adhesion molecules into tumor cells, suppression of transforming growth factor
      and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas
      interaction between tumor cells and attacking lymphocytes. With these approaches,
      it seems likely that gene therapy may become the fifth major modality of cancer
      treatment in the next decade.

PMID- 10068265
TI  - Testicular cancer: an oncological success story.
AB  - Testicular cancer has become a model for a curable neoplasm. Our studies with
      cisplatin combination chemotherapy allow us to conclude that: (a) short-duration
      intensive induction therapy with the most active agents in optimal dosage is more
      important than maintenance therapy; (b) modest dose escalation increases toxicity
      without improving therapeutic efficacy; (c) it is possible to develop curative
      salvage therapy for refractory germ cell tumors; and (d) preclinical models
      predicting synergism, such as vinblastine + bleomycin or cisplatin + etoposide
      have clinical relevance. Finally, testicular cancer has also become a model for
      new drug development. Cisplatin was approved by the Food and Drug Administration
      for testis and ovarian cancer, and etoposide and ifosfamide were approved for
      refractory germ cell tumors. The success of these studies confirms the importance
      of the continued search for new investigational drugs in all solid tumors.

PMID- 10068267
TI  - Combined modality therapy of lung cancer.
AB  - Combined modality therapy for lung cancer was first demonstrated to be successful
      in limited-stage small cell lung cancer. Concurrent administration of
      chemotherapy with chest and elective brain irradiation appears to produce the
      best results, with cisplatin/etoposide as the core chemotherapy. Using such
      programs, 2-year survival in the 40% range and 5-year survivals in excess of 20%
      may be expected, based on the results of multiple studies. Attempts to improve on
      these results through the use of altered schemes of chest irradiation or the
      delivery of high-dose consolidation chemotherapy are ongoing but to date have not
      been shown to affect survival significantly. We remain at a plateau in the
      effectiveness of combined modality therapy for small cell lung cancer, with
      little evidence that it impacts survival at all in extensive-stage disease. The
      incorporation of new agents in combination chemotherapy regimens, more "specific"
      immunotherapy directed at tumor-associated antigens, and the potential adjunctive
      use of broad-spectrum neuropeptide antagonists offer promise for the future. In
      non-small cell lung cancer, the sequential use of platinum-based chemotherapy and
      chest irradiation appears superior in survival to standard, daily fractionated
      radiation therapy used alone, with long-term survival increased from 5-10% to 15
      20%. Concurrent administration of chemotherapy with cisplatin/etoposide and chest
      irradiation produces 2-year survival in the range of 30%, about twice that would
      be expected for radiation therapy alone, but has not been compared to it in the
      setting of a randomized trial. Low-dose cisplatin on a daily basis has been
      combined as a "sensitizer" with chest irradiation, producing initial results that
      appeared encouraging. However, these have not been reproduced in subsequent,
      randomized trials. Another approach to combined modalities has been to give
      chemotherapy or chemotherapy/radiation therapy as induction, followed by surgical
      resection, with or without subsequent additional treatment. Most patients (80
      85%) can be resected, with encouraging survival at 2 and 3 years in the Southwest
      Oncology Group experience (37 and 26%, respectively). However, toxicity is
      greater, and such an approach is associated with an overall mortality risk in the
      range of 10%. A current intergroup study attempts to define the role of surgery
      in this setting. The major recent development that is likely to influence the
      future of combined modality therapy for this disease is the advent of multiple
      new chemotherapeutic agents, such as the taxanes, gemcitabine, vinorelbine, and
      the topoisomerase-I inhibitors, which have activity in stage IV disease. The
      immediate challenge is how to combine these agents with platinum analogues,
      radiation, and surgery. Aiding this process may be the use of molecular
      biological "markers" that may predict the chance of success or failure with a
      given systemic agent. The next decade is likely to see substantial improvements
      in the outcome of treatment for patients with stages I-III non-small cell lung
      cancer, based on the systemic exploration of combined modalities.

PMID- 10068266
TI  - Multimodality therapy for locally advanced and limited stage IV breast cancer:
      the impact of effective non-cross-resistance late-consolidation chemotherapy.
AB  - To determine the effectiveness of non-cross-resistant late-consolidation
      chemotherapy in locally advanced breast cancer (LABC) and stage IV breast cancer,
      we review our experience with two regimens. Between 1985 and 1991, we enrolled 56
      patients with LABC, who were treated with a doxorubicin-based adjuvant regimen,
      followed by a late-consolidation non-cross-resistant regimen containing
      methotrexate, 5-fluorouracil, cisplatin, and cyclophosphamide. Between 1985 and
      1996, a total of 45 patients with limited stage IV breast cancer underwent
      surgical excision of all evaluable disease, making them metastatic (stage IV)
      with no evaluable disease. Surgery was followed by a doxorubicin-containing
      regimen and then a late-consolidation non-cross-resistant regimen, which was
      either methotrexate, 5-fluorouracil, cisplatinum, and cyclophosphamide or 5
      fluorouracil, mitomycin, etoposide, and cisplatin. Twenty-four patients with
      limited bone metastases that were unresectable were treated with a doxorubicin
      containing regimen, radiation therapy to all sites of disease, and then one of
      the two late non-cross-resistant regimens. With a median follow-up of 84 months,
      78% of patients with LABC are alive, and 68% are free of disease. After a median
      follow-up of 44 months, 53% of patients with stage IV with no evaluable disease
      are alive and free of disease. The use of non-cross-resistant late-consolidation
      chemotherapy is an effective strategy in the treatment of patients with LABC and
      selected patients with limited stage IV breast cancer.

PMID- 10068268
TI  - Freireich's laws in the treatment of sarcomas.

PMID- 10068269
TI  - Can we cure indolent lymphomas?
AB  - The current consensus is that indolent lymphomas are incurable disorders. There
      are some indications that these malignancies are potentially curable. Indeed, not
      all indolent lymphomas are currently incurable. For example, patients with Ann
      Arbor stage I-II indolent lymphomas can experience long-term disease-free
      survival and probable cure. Also, from the available literature data, it seems
      that the achievement of a molecular complete remission is a desirable objective.
      Patients who achieve a persistently negative PCR state seldom relapse, whereas
      the opposite is true for persistently positive cases. In view of its excellent
      correlation with disease-free survival when examined serially in multiple blood
      or marrow samples, the PCR technique has the potential of providing a tumor
      marker that can be used as an early end point for clinical trials. By serving as
      an early surrogate end point, PCR could play an important role in expediting the
      development of new treatment strategies. Whether IFN is capable of increasing the
      molecular complete remission rate as measured by PCR is not known. However, it is
      clear that from the clinical standpoint, IFN has been able to increase 2-fold the
      length of remission in patients with advanced indolent lymphomas. In at least two
      studies, this has been associated with prolongation of survival. More intensive
      regimens such as alternating triple therapy, when used in combination with IFN,
      seem to have improved the quality of remissions as judged by the PCR assay.
      Finally, the site where the bcl-2 breakpoint occurs seems to have clinical
      significance. Those follicular lymphomas with germ-line bcl-2, in our experience,
      have behaved more aggressively than the others, and their failure-free survival
      seems different from the usual indolent lymphomas and more closely resembles the
      large cell lymphomas. Although the biological significance of this observation is
      not yet understood, this group might actually constitute a prognostically
      different subset with a more aggressive and perhaps more curable lymphoma.
      Whether the plateau observed in their failure-free survival curve will be
      maintained with more follow-up and whether they might be a curable subset remain
      to be determined.

PMID- 10068270
TI  - The evolution of antibiotic therapy for neutropenic patients.
AB  - Considerable progress has been made in the treatment of infections in neutropenic
      patients during the past three decades. A major contribution to this progress has
      been the discovery of effective new therapies and their prompt administration.
      Unfortunately, successful therapy of each important pathogen has resulted in the
      emergence of new pathogens, usually with unique patterns of antibiotic
      susceptibility. Unfortunately, antibiotic resistance has become an increasing
      threat in recent years, raising the possibility of infections that will be
      difficult to eradicate. Fortunately, there are new classes of antimicrobials that
      hold promise for therapeutic success in the future.

PMID- 10068271
TI  - Hematopoietic supportive care.

PMID- 10068273
TI  - Toward a leukemia treatment strategy based on the probability of stem cell death:
      an essay in honor of Dr. Emil J Freireich.
AB  - Dr. Emil J Freireich is a pioneer in the rational treatment of cancer in general
      and leukemia in particular. This essay in his honor suggests that the cell kill
      concept of chemotherapy of acute myeloblastic leukemia be extended to include two
      additional ideas. The first concept is that leukemic blasts, like normal
      hemopoietic cells, are organized in hierarchies, headed by stem cells. In both
      normal and leukemic hemopoiesis, killing stem cells will destroy the system;
      furthermore, both normal and leukemic cells respond to regulators. It follows
      that acute myelogenous leukemia should be considered as a dependent neoplasm. The
      second concept is that cell/drug interaction should be considered as two phases.
      The first, or proximal phase, consists of the events that lead up to injury; the
      second, or distal phase, comprises the responses of the cell that contribute to
      either progression to apoptosis or recovery. Distal responses are described
      briefly. Regulated drug sensitivity is presented as an example of how distal
      responses might be used to improve treatment.

PMID- 10068272
TI  - High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as
      conditioning regimen for allogeneic bone marrow transplantation for patients with
      acute myeloid leukemia in first complete remission.
AB  - We explored the combination of busulfan/cyclophosphamide/etoposide as
      conditioning regimen prior to bone marrow transplantation in 31 patients with
      acute myeloid leukemia (AML) in first complete remission. The preparative regimen
      consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg
      cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25
      patients are alive in continuous complete remission. Estimated disease-free
      survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft
      versus-host disease and cytomegalovirus infection, graft-versus-host disease and
      pneumonia, sepsis and mucositis, respectively). None of the patients have
      relapsed. As demonstrated by the results of this analysis, the conditioning
      regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in
      patients with AML in first complete remission. Main nonhematological toxicities
      were mucositis and hepatotoxicity. The low mortality and relapse rate appears to
      justify allogeneic bone marrow transplantation for patients with AML in first
      complete remission who have an HLA-identical donor. Whether this regimen offers a
      substantial improvement in disease-free and overall survival over presently used
      regimens warrants further investigation.

PMID- 10068274
TI  - Prospects for cytokine and chemokine biotherapy.
AB  - Cytokines with immunostimulating effects have the capacity to induce tumor
      immunity in animal models, whereas some cytokines interfere with tumor growth
      based on their angiostatic effects. Despite these capabilities, cytokines, such
      as IFN-, IFN-, tumor necrosis factor, interleukin (IL)-1, and IL-2, have had
      limited clinical efficacy and many undesirable side effects. In preclinical
      models, cytokines can even promote tumor growth and increase metastatic spread.
      Although chemokines have had limited clinical evaluation, studies of animal
      models show that they can also have tumor-suppressive or tumor-enhancing effects.
      In mice, chemokines, such as IP-10, RANTES, and TCA3, have resulted in tumor
      regression and immunity to subsequent tumor challenge. Those chemokines that are
      angiostatic (e.g., PF4, IP-10, and MIG) can also induce tumor regression by
      reducing the tumor blood supply. Conversely, IL-8, which is angiogenic, can
      promote tumor growth. Our studies show that nasopharyngeal cell line cells (FADU)
      show a chemotactic as well as a proliferative response to MCP-1. In addition, a
      variant murine T cell lymphoma cell line Esb-MP, unlike the parental variant Esb,
      was selectively chemoattracted by murine MCP-1/JE. When injected s.c. into mice,
      the Esb-MP variant metastasized to the kidney with much higher frequency than the
      Esb variant. Both cultured kidneys from normal mice and a mesangial cell line
      constitutively produced chemoattractants that acted on Esb-MP but not Esb
      parental cells. Purification to homogeneity of these chemoattractants led to the
      identification of RANTES and JE. These results demonstrate that some chemokines
      may promote tumor growth and organ-specific metastatic spread of those tumors
      that have adapted and become responsive to chemokines. Finally, tumors appear to
      use numerous adaptive mechanisms to subvert and suppress the immune system. More
      effective therapy with cytokines and chemokines will require better
      characterization of the means by which tumors develop resistance to cytokines and
      overcome the immune system. Only then can we develop appropriate therapeutic
      approaches to antagonize cancer-induced immunosuppression.

PMID- 10068275
TI  - Oncogenes and tumor suppressor genes: therapeutic implications.
AB  - Genetic instability is a hallmark of cancer. Alterations in DNA through
      mutations, deletions, and translocations affect genes that are fundamental to
      normal cell growth differentiation and programmed cell death. Here, we discuss
      these alterations as they relate to oncogenes and tumor suppressor genes. In
      addition, we describe the implications the changes in oncogenes and tumor
      suppressor genes have on designing new therapeutic strategies for the treatment
      of cancer.

PMID- 10068276
TI  - Disorders in cell circuitry associated with multistage carcinogenesis:
      exploitable targets for cancer prevention and therapy.
AB  - The development of a malignant tumor involves the progressive acquisition of
      mutations and epigenetic abnormalities in multiple genes that have highly diverse
      functions. Some of these genes code for pathways of signal transduction that
      mediate the action of growth factors. The enzyme protein kinase C plays an
      important role in these events and in the process of tumor promotion. Therefore,
      we examined the effects of three inhibitors of protein kinase C, CGP 41251, RO 31
      8220, and calphostin C, on human glioblastoma cells. These compounds inhibited
      growth and induced apoptosis; these activities were associated with a decrease in
      the level of CDC2 and cyclin B1/CDC2-associated kinase activity. This may explain
      why the treated cells accumulated in G2-M. In a separate series of studies, we
      examined abnormalities in cell cycle control genes in human cancer. We have found
      that cyclin D1 is frequently overexpressed in a variety of human cancers.
      Mechanistic studies indicate that cyclin D1 can play a critical role in
      carcinogenesis because: overexpression enhances cell transformation and
      tumorigenesis; introduction of an antisense cyclin D1 cDNA into either human
      esophageal or colon cancer cells reverts their malignant phenotype; and
      overexpression of cyclin D1 can enhance the amplification of other genes. The
      latter finding suggests that cyclin D1 can enhance genomic instability and,
      thereby, the process of tumor progression. Therefore, inhibitors of the function
      of cyclin D1 may be useful in both cancer chemoprevention and therapy. We
      obtained evidence for the existence of homeostatic feedback loops between cyclins
      D1 or E and the cell cycle inhibitory protein p27Kip1. On the basis of these and
      other findings, we hypothesize that, because of their disordered circuitry,
      cancer cells suffer from "gene addiction" and "gene hypersensitivity," disorders
      that might be exploited in both cancer prevention and therapy.

PMID- 10068277
TI  - Epidermal growth factor receptor inhibition by a monoclonal antibody as
      anticancer therapy.
AB  - Monoclonal antibody (mAb) 225 against the human epidermal growth factor receptor
      blocks activation of receptor tyrosine kinase. This retards or arrests cell cycle
      progression, with accumulation of cells in G1 phase. The mechanism of growth
      inhibition involves increased levels of p27KIP1 and inhibition of cyclin
      dependent kinase-2 activity. mAb in combination with chemotherapy exhibits a
      synergistic antitumor activity, with successful eradication of well-established
      tumor xenografts that resist treatment with either mAb or drug alone. A Phase I
      clinical trial has established the safety of repeated administration of
      human:mouse chimeric mAb 225 at concentrations that maintain receptor-saturating
      blood levels for up to 3 months. Phase I trials exploring mAb 225 treatment in
      combination with doxorubicin, cisplatin, or paclitaxel are ongoing.

PMID- 10068278
TI  - Summary of the first Emil J Freireich symposium.

PMID- 10068279
TI  - Who took the clinical out of clinical research?--Mouse versus man: seventh David
      A Karnofsky Memorial Lecture--1976.

PMID- 10068280
TI  - Chronic myelogenous leukemia--progress at the M. D. Anderson Cancer Center over
      the past two decades and future directions: first Emil J Freireich Award Lecture.
AB  - The purpose of this study was to review the progress in clinical and
      translational research in chronic myelogenous leukemia (CML) over the past 20
      years at M.D. Anderson Cancer Center. The CML database updating the clinical and
      basic research investigations was reviewed as the source of this report.
      Publications resulting from these investigations were summarized. The long-term
      results with intensive chemotherapy, IFN-alpha therapy alone or in combination,
      autologous stem cell transplantation, and new agents such as homoharringtonine
      and decitabine showed encouraging results. Biological studies related to the BCR
      ABL molecular abnormality, other molecular events, and the detection of minimal
      residual disease were detailed. Future strategies with potential promise in CML
      were outlined. Significant progress in understanding CML biology and in treating
      patients afflicted with the disease has occurred. Several therapeutic and
      research tools are currently investigated, which should hopefully improve further
      the prognosis of patients with CML.

PMID- 10068281
TI  - Implanon. A review of clinical studies.

PMID- 10068282
TI  - Proceedings of a symposium on genetics and tuberculosis. Cape Town, South Africa,
      18-20 November 1997.

PMID- 10068283
TI  - Biopolymers, Model systems. Web alert.

PMID- 10068284
TI  - Ipsilateral femoral neck and shaft fractures.

PMID- 10068285
TI  - Rapid liquid chromatography with tandem mass spectrometry-based screening
      procedures for studies on the biotransformation of drug candidates.
AB  - The accelerated pace of contemporary drug discovery and development in the
      pharmaceutical industry has generated increasing demands for early information on
      the metabolic fate of candidate drugs to guide the selection of new compounds for
      clinical evaluation. In response to these demands, we have developed a procedure
      for the rapid analysis of complex biological mixtures for the presence of drug
      related materials and have embarked on the development of novel computer-based
      approaches whereby such procedures can be automated. The goal of this work was to
      rapidly identify drug metabolites (derived either from a single substrate or from
      a mixture of substrates) formed in vivo or in vitro. The approach that we have
      developed relies on the use of generic chromatographic and mass spectrometric
      methods for analysis of mixtures of drugs and metabolites and on correlation
      analysis of tandem mass spectrometry spectra to distinguish drug-related
      components from endogenous materials. Cross-correlation of the spectra also is
      used to identify the relationship between each metabolite and its respective
      parent drug in the mixture. In this manner, metabolites of a mixture of several
      drugs may be analyzed in the time it normally would take to analyze the products
      from a single substrate. We show that this rapid analytical approach can, with
      only minor sacrifices in the completeness of the data, significantly increase the
      number of compounds whose metabolic fate can be elucidated in a given time.

PMID- 10068286
TI  - Meeting of the minds on mercury.

PMID- 10068287
TI  - New understanding of algae.

PMID- 10068288
TI  - Alzheimer's disease: a basis in bacteria?

PMID- 10068289
TI  - Gene-toxicant link to Parkinson's disease.

PMID- 10068290
TI  - Ninth ROC rocks the boat. Report on Carcinogens.

PMID- 10068291
TI  - Dietary exposure to PCBs and dioxins in children.

PMID- 10068292
TI  - Festschrift in honour of Stover Snook.

PMID- 10068293
TI  - [The Academician Vasilii Vasil'evich Parin Lectures (18 March 1998, Moscow)].

PMID- 10068294
TI  - [The V. V. Parin Memorial Study Room in the Medical Museum Research Center of the
      Russian Academy of Medical Sciences].

PMID- 10068295
TI  - Intracellular location of catalase-peroxidase hydroperoxidase I of Escherichia
      coli.
AB  - The catalase-peroxidase hydroperoxidase I of Escherichia coli has been confirmed
      to be located in the cytoplasm using two independent methods. Catalase activity
      was found predominantly (> 95%) in the cytoplasmic fraction following spheroplast
      formation. The cytoplasmic enzyme glucose-6-phosphate dehydrogenase and the
      periplasmic enzyme alkaline phosphatase were used as controls. The second method
      of immunogold staining for the enzyme in situ revealed an even distribution of
      the enzyme across the cell.

PMID- 10068296
TI  - Impact of new therapies on Alzheimer's disease management. Introduction.

PMID- 10068297
TI  - [Cerebrovascular disorder with memory disturbance, drowsiness, and a lack of
      drive as major symptoms].

PMID- 10068298
TI  - Article retraction.

PMID- 10068299
TI  - Proceedings of the 52nd annual fall conference of the American Hearth Association
      Council for High Blood Pressure Research. Philadelphia, Pennsylvania, USA.
      September 15-18, 1998.

PMID- 10068300
TI  - Hoechst Marion Roussel Hypertension Research Clinical Fellowship Award 1998.

PMID- 10068301
TI  - Irvine Page-Alva Bradley Lifetime Achievement Award 1998.

PMID- 10068302
TI  - Novartis Award for Hypertension Research 1998.

PMID- 10068304
TI  - [Guidelines for quality assurance in dermatology].

PMID- 10068303
TI  - Harry Goldblatt Award 1998.

PMID- 10068305
TI  - [Anesthesia and environmental pollution].

PMID- 10068308
TI  - Early developmental changes in the chemoarchitecture of the human inferior olive:
      a review.

PMID- 10068309
TI  - Neuronal nitric oxide synthase expression in developing and adult human CNS.
AB  - Neuronal nitric oxide synthase (nNOS) is constitutively expressed by
      subpopulations of neurons in the CNS and is involved in neurotransmission,
      learning and memory, and neuronal injury. While the distribution of nNOS neurons
      has been characterized in the rodent CNS, the expression in human brain has not
      been well documented. We determined the expression of nNOS in second trimester
      human fetal and adult brain. In second trimester fetal brain, the nNOS neurons
      are concentrated in the developing cerebral cortex at the subplate zone and in
      layer VI, the striatum, and in certain brainstem nuclei. The nNOS neurons are
      sparsely distributed in the hippocampus, and virtually absent in the cerebellar
      cortex. The nNOS neurons in the subplate zone extend their processes radially,
      suggesting a developmental role, perhaps in guidance. The number and distribution
      of NADPH diaphorase-positive neurons corresponds to that of the nNOS neurons.
      While the distribution of nNOS neurons in the adult brain is similar to that
      found in fetal brain, the overall density is lower in the adult. The highest
      density of nNOS neurons is found in the striatum followed by the neocortex. A
      region-specific role for nNOS neurons in human brain and a potential
      developmental role for nNOS in the cerebral cortex are suggested by these data.

PMID- 10068310
TI  - Temporal lobe microdysgenesis in epilepsy versus control brains.
AB  - Histopathologic evaluation of brain tissue derived from surgically treated
      patients with medically refractory temporal lobe epilepsy (TLE) frequently
      reveals structural brain lesions in the surgical specimen. While several of the
      most commonly encountered lesions such as low-grade neoplasms or vascular
      malformations are well established as structural substrates of epilepsy, the
      significance of subtle microscopic characteristics has remained controversial.
      Within the spectrum a broad range of microscopic features has previously been
      reported as "mild cortical dysplasia," "focal cortical dysplasia," or
      "microdysgenesis," including cortical laminar disorganization, columnar
      arrangement of cortical neurons, marked clustering of neurons throughout cortical
      layers II-VI, increased numbers of molecular layer neurons, marked perivascular
      clustering of oligodendroglia in the white matter, single heterotopic neurons in
      the deep white matter, glioneuronal hamartia, giant neurons, and balloon cell
      change. In this paper we report the frequency of these features in temporal lobe
      tissue of 47 surgically treated TLE-patients vs 29 normal autopsy controls. While
      most of them were found in both cases and controls, clustering of neurons
      throughout cortical layers II-VI, perivascular clustering of oligodendroglia in
      the white matter, increased single heterotopic white matter neurons, and
      glioneuronal hamartias predominated in tissue from patients with epilepsy (p <
      0.05). A count of more than 10 white matter neurons/HPF was associated with a
      worse postoperative outcome (p < 0.05). These data suggest that certain
      microscopic characteristics are associated with the epileptic process, while
      others appear as normal variants.

PMID- 10068311
TI  - Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.
AB  - Sleep disruption and other circadian rhythm disturbances are frequently seen in
      dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN),
      the putative site of the hypothalamic circadian pacemaker, to determine the
      nature and degree of pathologic changes caused by severe dementia.
      Neuropathologic examination indicated that among 30 patients with a clinical
      history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease,
      3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had
      severe hippocampal sclerosis. Comparisons were made with a control group composed
      of 13 age-matched patients with no clinical or pathological evidence of dementia
      or other CNS disorders. To determine the pathologic involvement within the SCN,
      human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and
      specific antibodies directed against vasopressin (VP), neurotensin (NT),
      neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4)
      and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily
      limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse
      plaques were noted. The pathologic changes within the SCN were less severe than
      in the other brain regions. Morphometric analysis was accomplished using a
      stereological approach to sample the average total number of positively stained
      neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal
      subdivision of the SCN. Patients with Alzheimer disease exhibited a significant
      decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63,
      p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained
      astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies
      provide evidence that both vasopressin and neurotensin neurons are lost in
      Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of
      disease-related pathology within the SCN. Taken collectively, our data support
      the hypothesis that damage to the SCN may be an underlying anatomical substrate
      for the clinically observed changes in circadian rhythmicity that have been
      observed in Alzheimer patients.

PMID- 10068312
TI  - Molecular genetic analysis as a tool for evaluating stereotactic biopsies of
      glioma specimens.
AB  - Over the last years, distinct genetic lesions have been associated with
      individual tumor entities. Stereotactic biopsy has become an essential diagnostic
      tool in surgical neuro-oncology. In order to evaluate the potential of molecular
      analyses in stereotactic biopsies, we examined a series of 156 human brain tumors
      from patients undergoing stereotactic biopsy for molecular alterations typically
      seen in astrocytic gliomas and compared those results with a control group of 268
      astrocytic tumors obtained at open surgery. Stereotactic biopsies of astrocytomas
      with borderline histopathological features between the WHO grades II and III
      showed a higher rate of allelic losses on chromosome 10 than those of the WHO
      grade II from open surgery (p = 0.011). Stereotactic biopsies of astrocytomas
      with borderline histopathological features between the WHO grades III and IV
      showed a higher rate of allelic losses on chromosome 10 than those of the WHO
      grade III from open surgery (p = 0.013). This indicates that stereotactic
      biopsies with features intermediate between grades are likely to correspond to
      the higher malignancy grade. Our data demonstrate that molecular genetic
      approaches can be successfully applied to stereotactic glioma biopsies. The
      difference in the distribution of malignancy associated genetic alterations
      between a stereotactic and openly resected group of gliomas indicates that
      histopathology may underestimate the malignant potential in some stereotactic
      specimens. We propose to further evaluate the molecular analysis of stereotactic
      glioma biopsies as a useful adjunct to standard histopathological procedures.

PMID- 10068313
TI  - Cellular proliferation in pilocytic and diffuse astrocytomas.
AB  - Using quantitative image analysis, we evaluated the MIB-1 labeling index (LI) in
      a large population of pilocytic (n = 131) and diffuse astrocytomas (n = 140),
      explored its significance as a prognostic predictor of survival, and compared it
      to other commonly accepted predictors, including grade and its histologic
      determinants, atypia, mitoses, endothelial proliferation, and necrosis. Diffuse
      astrocytomas were graded according to the St Anne-Mayo scheme and included 45
      grade 2, 50 grade 3, and 45 grade 4 astrocytomas. In pilocytic astrocytomas,
      mean, median, and range of MIB-1 LIs were 1.1, 0.9, and 0-3.9%, respectively. In
      diffuse astrocytomas, these values were 2.3, 2, and 0-7.6% in grade 2; 6, 4.4,
      and 0.1-25.7% in grade 3; 9.1, 6, and 0.3-36% in grade 4. There was a significant
      difference in the distribution of MIB-1 LIs between pilocytic and diffuse grade 2
      astrocytomas (p < 0.001), between grade 2 and grade 3 (p < 0.001), and between
      tumors of grade 3 and 4 (p = 0.014). Among pilocytic astrocytomas there was no
      association between survival and MIB-1 LI or any histologic parameter. In diffuse
      astrocytomas, MIB-1 LI was significantly correlated with grade as well as with
      mitotic activity (<0.001) and survival. While in diffuse astrocytomas of all
      grades, necrosis was the strongest factor associated with survival, in tumors of
      grades 2 and 3 the MIB-1 LI preceded other histologic parameters and, on
      multivariate analysis, remained the only feature predictive of survival. Grade 3
      astrocytomas with a single "solitary" mitosis had a significantly lower MIB-I LI
      than did grade 3 tumors with >1 mitosis and, compared to the latter, had a
      significantly longer survival (p = 0.013), one not significantly different from
      patients with grade 2 astrocytomas. These findings suggest that the cutoff point
      between grade 2 and 3 in the St. Anne-Mayo scheme may not be optimal and may need
      to be revised.

PMID- 10068314
TI  - A syngeneic mouse glioma model for study of glioblastoma therapy.
AB  - Animal models of human tumors serve a vital role in the development and testing
      of new anticancer therapies. Since the immune system is likely to play an
      essential role in tumor eradication, there is a particular need for modeling
      human disease in immunocompetent hosts. Few models of glioma have been developed
      in immunocompetent mice that are commercially available and none of these tumors
      have histological and antigenic characteristics of human gliomas. We have used a
      cell line, 4C8, derived from a spontaneous glioma-like tumor that arose in a
      transgenic mouse to develop a new glioma model. The intracranial injection of 4C8
      cells into immunocompetent syngeneic B6D2F1 mice resulted in tumors that were
      densely cellular, developed a pseudopallisading pattern of necrosis, and
      expressed GFAP; all important features of human malignant gliomas. The average
      neurological endpoint was 51 days after intracranial injection. The 4C8 cells
      also grew rapidly in the flank, retaining histologic features seen in
      intracranial tumors. Flank tumors reached an average volume of 100 mm3, a volume
      ideal for therapy testing, by 34 days postinjection. These results suggest that
      the 4C8 mouse glioma model is an excellent system in which to test new antiglioma
      therapies for use in humans.

PMID- 10068315
TI  - Regulation of the gene encoding tumor necrosis factor alpha (TNF-alpha) in the
      rat brain and pituitary in response in different models of systemic immune
      challenge.
AB  - Tumor necrosis factor (TNF)-alpha is usually referred to as a proinflammatory
      cytokine that plays a central role in initiating the cascade of other cytokines
      and factors for an appropriate immune response to infection. Like systemic
      phagocytes, recent studies have reported that specific cellular populations of
      the CNS have the ability to express and release the proinflammatory cytokine in
      response to peripheral administration of the bacterial endotoxin
      lipopolysaccharide (LPS). Whether such phenomenon represents a general mechanism
      of systemic immunogenic stimuli and how the severity of the challenge may
      influence TNF-alpha transcription in the brain has yet to be defined. Adult male
      rats were sacrificed 1, 3, 6, 12, 24 and 48 hours (h) after intraperitoneal (IP)
      injection of LPS (25-250 microg/100 g) or intramuscular (IM) injection of
      turpentine. Brains and pituitary glands were removed, cut, and TNF-alpha mRNA
      assayed by in situ hybridization using a full-length rat cRNA probe. The results
      show no positive signal under basal conditions or following sterile inflammation
      into the left hind limb. Systemic LPS caused a profound increase in the
      expression of the gene encoding TNF-alpha in the leptomeninges, choroid plexus
      (chp) and all sensorial circumventricular organs (CVOs). Interestingly, a
      migratory-like pattern of TNF-alpha-positive cells became apparent around the
      sensorial CVOs at 3 h, while a ubiquitous-like positive signal was found
      throughout the brain 6 h after the injection with the highest dose of LPS. The IP
      LPS injection also stimulated TNF-alpha transcription in the anterior pituitary
      lobe; the signal was maximal 1 h after the injection and returned gradually to
      basal levels at 12 h, whereas the mRNA encoding the cytokine was detected later
      in the neurohypophysis, i.e. 3 and 6 h post challenge. Dual-labeling procedure
      provided the evidence of an LPS-dependent induction of TNF-alpha in different
      phagocytic cellular populations of the brain, including parenchymal microglial
      cells during severe endotoxemia. The fact that these myeloid-derived cells have
      the ability to express the LPS receptor CD14 in the brain may well explain the
      transcriptional activation of the cytokine in response to the bacterial
      endotoxin, but not to systemic localized inflammation.

PMID- 10068316
TI  - Absence of spontaneous central nervous system remyelination in class II-deficient
      mice infected with Theiler's virus.
AB  - We previously showed that Theiler's murine encephalomyelitis virus (TMEV)
      infected major histocompatibility complex (MHC) class II-deficient mice develop
      both demyelination and neurologic deficits, whereas MHC class I-deficient mice
      develop demyelination but no neurologic deficits. The absence of neurologic
      deficits in the class I-deficient mice was associated with preserved sodium
      channel densities in demyelinated lesions, a relative preservation of axons, and
      extensive spontaneous remyelination. In this study, we investigated whether TMEV
      infected class II-deficient mice, which have an identical genetic background
      (C57BL/6 x 129) as the class I-deficient mice, have preserved axons and
      spontaneous myelin repair following chronic TMEV-infection. Both class I- and
      class II-deficient mice showed similar extents of demyelination of the spinal
      cord white matter 4 months after TMEV infection. However, the class I-deficient
      mice demonstrated remyelination by oligodendrocytes, whereas class II-deficient
      mice showed minimal if any myelin repair. Demyelinated lesions, characterized by
      inflammatory infiltrates in both mutants, revealed disruption of axons in class
      II- but not class I-deficient mice. Further characterization revealed that even
      though class II-deficient mice lacked TMEV-specific IgG, they had virus-specific
      IgM, which, however, did not neutralize TMEV in vitro. In addition, class II
      deficient mice developed TMEV-specific cytotoxic T-lymphocytes in the CNS during
      the acute (7 days) disease, but these cytotoxic lymphocytes were not present in
      the chronic stage of disease, despite a high titer of infectious virus throughout
      the disease. We envision that the presence of demyelination, high virus titer,
      absence of remyelination, and axonal disruption in chronically infected class II
      deficient mice contributes to the development of paralytic disease.

PMID- 10068317
TI  - Prenatal methylazoxymethanol treatment in rats produces brain abnormalities with
      morphological similarities to human developmental brain dysgeneses.
AB  - A double methylazoxymethanol (MAM) intraperitoneal injection was prenatally
      administered to pregnant rats at gestational day 15 to induce developmental brain
      dysgeneses. Thirty adult rats from 8 different progenies were investigated with a
      combined electrophysiological and neuroanatomical analysis. The offspring of
      treated dams was characterized by extensive cortical layering abnormalities,
      subpial bands of heterotopic neurons in layer I, and subcortical nodules of
      heterotopic neurons extending from the periventricular region to the hippocampus
      and neocortex. The phenotype of cell subpopulations within the heterotopic
      structures was analyzed by means of antibodies raised against glial and neuronal
      markers, calcium binding proteins, GABA, and AMPA glutamate receptors. Neurons
      within the subcortical heterotopic nodules were characterized by abnormal firing
      properties, with sustained repetitive bursts of action potentials. The
      subcortical nodules were surrounded by cell clusters with ultrastructural
      features of young migrating neurons. The immunocytochemical data suggested,
      moreover, that the subcortical heterotopia were formed by neurons originally
      committed to the neocortex and characterized by morphological features similar to
      those found in human periventricular nodular heterotopia. The present study
      demonstrates that double MAM treatment at gestational day 15 induces in rats
      developmental brain abnormalities whose anatomical and physiological features
      bear resemblance to those observed in human brain dysgeneses associated with
      intractable epilepsy. Therefore, MAM treated rats could be considered as useful
      tools in investigating the pathogenic mechanisms involved in human developmental
      brain dysgeneses.

PMID- 10068318
TI  - [Pediatric tonsillectomy can be performed as day surgery].
AB  - In the spring of 1996, tonsillectomy, traditionally regarded as a procedure
      requiring hospitalization, began to be performed at the recently started day
      surgery unit at Danderyd Hospital. The article consists in a report of results
      obtained with a series comprising just over 200 children who were the first to
      undergo adenotonsillectomy in day surgery, and followed up, for instance, by
      questionnaire. There were no cases of complications requiring hospitalization
      during the first postoperative day. The parents were fairly satisfied with the
      care provided, though 25 per cent of them said that in the event of a new
      operation being necessary they would prefer that it be performed as an in-patient
      procedure.

PMID- 10068319
TI  - [A cat at home can cause nasal congestion at work].

PMID- 10068320
TI  - [Amoxicillin caused aseptic meningoencephalitis].

PMID- 10068321
TI  - [To know that the physician is really listening].
AB  - Communication is a central feature of patient-doctor interaction, and one that is
      often problematic. Listening is so basic that we tend to take it for granted.
      Unfortunately, most of us think ourselves better listeners than we really are.
      Especially distressing are deaf ears among those we count on for understanding.
      Doctors are powerful social figures, expected to manifest appropriate skills in
      encountering anxious, unhappy, disappointed, angry or even hypochondriac
      patients. The article consists in a review of an interview method based on
      cognitive principles, specially designed to promote the patient's feeling of
      being listened to, and to establish a working relationship. Such skills as non
      verbal communication, reflection, summation, and self-disclosure are essential
      components of the method. The patient's emotional response to health problems is
      viewed as being valid, and investigation is initiated on the basis of the
      patient's perception of the problem rather than on the doctor's professional
      knowledge. Through Socratic questioning, the doctor helps patients to reach their
      own conclusions and to reformulate axiogenic hypothesis.

PMID- 10068322
TI  - [Effects of strength and endurance training on skeletal muscles in the elderly.
      New muscles for old!].
AB  - A well-known effect of increasing age is the gradual reduction of muscle
      function, and thus of performance in the activity of daily living. Recent
      research has shown that, even among the very elderly, exercise can improve not
      only strength and endurance, but also balance and mobility, thus reducing the
      risk of falls. The possibility of counteracting some of the age-related muscle
      changes has also been demonstrated. The article reviews current knowledge of
      strength and endurance training in the elderly, the importance of exercise to
      improve physical performance, and how lifelong exercise can counteract the
      effects associated with the ageing of the neuromuscular system.

PMID- 10068323
TI  - [Osteoporosis is prevented by physical activity, calcium and hormone
      supplementation].
AB  - As the incidence of osteoporosis-related fractures is increasing and constitutes
      a major health problem in the Western world, their prevention is of great
      importance. Physical activity, combined with adequate calcium intake and hormone
      levels, is necessary for the formation and maintenance of bone tissue. The
      effects of physical exercise on bone tissue variables are most beneficial when it
      is intensive, regular, and of weight-bearing character. Physical exercise may
      also be of value in the future treatment of osteoporosis. In addition to its
      skeletal effects, such exercise improves physical fitness, muscle strength and co
      ordination, resulting in a reduced risk of fractures and improved quality of
      life.

PMID- 10068324
TI  - [Physical inactivity and cancer--is this a causal relationship?].
AB  - Strong epidemiological evidence suggests relationship to exist between physical
      inactivity and the risk of large bowel cancer (especially colon cancer).
      Moreover, there are indications that inactivity is also associated with an
      increased risk of endogenous hormone-related cancer (especially breast cancer).
      However, further research is needed to determine whether such relationships are
      casual, and if so to identify the underlying mechanisms. Since a large proportion
      of the populations of industrial countries are characterized by a sedentary
      lifestyle, even a small risk may be associated with high attributable fraction.
      Moreover, not only are the types of cancer concerned common, but inactivity is
      also associated with a number of other chronic diseases. Accordingly, the health
      benefit to be derived from a general increase in physical activity might be
      substantial.

PMID- 10068325
TI  - [Sensitive quality indicators stimulate improvement of care].
AB  - For the past four years, 52 of the approximately 80 departments of medicine in
      Sweden have collected data on key indicators of quality of care with regards to
      acute myocardial infarction, stroke, anticoagulant treatment, and diabetes. The
      results are analysed centrally, each department being supplied with feedback in
      the form of overall results, and comparison of its own values with the respective
      means. Gradual general improvement has been discernible over time, though there
      is still room for improvement at some departments. There have been isolated
      instances of manifest changes in indicator values associated with major
      departmental reorganisation, probably reflecting real deterioration in quality of
      care. Thus, indicator monitoring would appear a sensitive means of promoting
      qualitative improvement.

PMID- 10068326
TI  - Rates of death from coronary heart disease.

PMID- 10068327
TI  - Rates of death from coronary heart disease.

PMID- 10068328
TI  - Dilated cardiomyopathy in HIV-infected patients.

PMID- 10068329
TI  - Dilated cardiomyopathy in HIV-infected patients.

PMID- 10068330
TI  - Dilated cardiomyopathy in HIV-infected patients.

PMID- 10068331
TI  - Warfarin-induced skin necrosis in a patient with a mutation of the prothrombin
      gene.

PMID- 10068332
TI  - The care of patients undergoing hemodialysis.

PMID- 10068333
TI  - The care of patients undergoing hemodialysis.

PMID- 10068334
TI  - The care of patients undergoing hemodialysis.

PMID- 10068335
TI  - The care of patients undergoing hemodialysis.

PMID- 10068336
TI  - Gamma/delta T-cell stimulation by pamidronate.

PMID- 10068337
TI  - Case 31-1998: a boy with bronchiectasis.

PMID- 10068338
TI  - Zygotic splitting after assisted reproduction.

PMID- 10068340
TI  - The Internet and nursing research.

PMID- 10068339
TI  - Truth or consequences?

PMID- 10068341
TI  - Expression of cyclin A and D proteins in prostate cancer and their relation to
      clinopathological variables and patient survival.
AB  - BACKGROUND: Cell proliferation and its regulation are important determinants of
      the prognosis of prostate cancer patients. Cyclins are important regulators of
      cell proliferation in human cancer, but their prognostic value has not been
      previously analyzed in prostate cancer. METHODS: The immunohistochemical
      expression and prognostic value of cyclins A and D were studied in prostate
      cancer in a cohort of 213 patients followed-up for a mean of 12 years. RESULTS:
      The expression of cyclin A was both cytoplasmic and nuclear, whereas the
      expression of cyclin D was nuclear. The mean (SD) fraction of cyclin A- and
      cyclin D-positive cells was 2.1 (7.9)% and 16.3 (23.4)%, respectively. The
      expression of cyclin A was related to TM-category, histological differentiation,
      perineural invasion, S-phase fraction, and expression of Ki67 and bcl-2 (for all,
      P<0.05). The expression of cyclin D was related to TM-classification,
      histological differentiation, perineural invasion, DNA ploidy, S-phase fraction,
      expression of Ki67, and mitotic index (for all, P< or =0.01). In survival
      analysis, expression of cyclin A predicted cancer-related survival in the entire
      cohort (P<0.001). Expression of cyclin D predicted cancer-related survival in the
      entire cohort (P<0.0001), in MO (P = 0.0007), and in T1-2NxM0 tumors (P =
      0.0003). In Cox multivariate analysis, T-category, M-category, patient age, and
      the fraction of cyclin A-positive cells were independent predictors of survival
      in the entire series. In local tumors, T-category, Gleason score, DNA ploidy, or
      S-phase fraction were independent prognostic factors, and cyclins had no
      independent prognostic value. CONCLUSIONS: The results show that the expression
      of cyclins A and D is related to several malignant cellular features in prostate
      cancer, but they have no independent prognostic value.

PMID- 10068342
TI  - Tissue PSA from fine-needle biopsies of prostatic carcinoma as related to serum
      PSA, clinical stage, cytological grade, and DNA ploidy.
AB  - BACKGROUND: The mechanisms behind changes in serum PSA (S-PSA) levels in patients
      with prostatic carcinoma (CAP) are not completely known. To further elucidate the
      factors affecting the serum levels of this important tumor marker, we measured
      PSA concentrations in serum and in aspiration biopsies (tissue PSA; T-PSA) from
      patients with prostatic disease and correlated the values to tumor stage,
      cytological grade, and DNA ploidy. METHODS: T-PSA and S-PSA were measured in 91
      metastasis-free patients with newly diagnosed, untreated CAP and 13 patients with
      benign prostatic hyperplasia, and the values were related to tumor stage,
      cytological grade, and DNA ploidy. RESULTS: Significant negative correlations
      were found between T-PSA and S-PSA in the total clinical material and various
      subgroups of patients with CAP. T-PSA showed significant negative associations to
      T-stage and to cytological grading, and T-PSA concentrations were significantly
      lower in tetra-/aneuploid tumors than in diploid tumors. On the other hand, S-PSA
      showed corresponding positive associations and was significantly higher in tetra
      /aneuploid tumors than in diploid tumors. CONCLUSIONS: The negative association
      between S-PSA and T-PSA values indicates that S-PSA values in metastasis-free
      patients reflect the degree of leakage from the tumor tissue rather than the
      intracellular concentration of PSA. Factors such as tissue volume, condition of
      gland structure, and vascularization may thus be more important for S-PSA than
      the production of PSA in the prostatic tissue.

PMID- 10068343
TI  - Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer:
      seventeen-year follow-up of the prospective basel study.
AB  - BACKGROUND: Prostate cancer has one of the highest incidence rates of all
      cancers. Vitamin intake and tobacco use may have an impact on incidence and
      mortality, but epidemiologic evidence is scarce and inconsistent. METHODS: Plasma
      vitamins C, E, retinol, and carotene were measured in 1971-1973 in 2,974 men
      working in Basel, Switzerland. In 1990, the vital status of all participants was
      assessed. RESULTS: Two hundred and ninety men had died from cancer, including 30
      with prostate cancer. On average, prostate cancer cases were 15 years older and
      smoked slightly more frequently than survivors. The mean values of plasma
      carotene, and of vitamin C, were nonsignificantly lower in prostate cancer cases
      than in survivors. After calculation of relative risk using the Cox model with
      exclusion of mortality during the first 2 years of follow-up, low vitamin E
      levels in smokers were related to an increased risk for prostate cancer. Relative
      risks of low vitamin C and carotene levels were about 1. A slightly but
      nonsignificantly increased risk was observed for low levels of retinol.
      CONCLUSIONS: Given the profound implication if the risk of prostatic cancer could
      be reduced, the relationship with vitamin E and smoking requires further study.

PMID- 10068344
TI  - Characterization of the role of IL-6 in the progression of prostate cancer.
AB  - BACKGROUND: We recently identified IL-6, a pleiotropic cytokine implicated in the
      neoplastic process of a variety of neoplasms, as a mediator of prostate cancer
      morbidity. In the present study, we investigated the expression of members of the
      IL-6 supergene family and related cytokines and the potential role of IL-6 in
      prostate cancer growth regulation. METHODS: Five established human prostate
      cancer cell lines were screened by ELISA for production of granulocyte colony
      stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary
      neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF),
      interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM
      CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80,
      was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and
      immunoblotting were performed to assay for expression of the signal-transducing
      component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were
      assessed by MTT assays. RESULTS: The three hormone-refractory cell lines, DU-145,
      TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF;
      TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing
      IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC
      and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed.
      None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All
      cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130.
      Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no
      effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited
      growth of hormone-refractory cells. CONCLUSIONS: IL-6 appears to undergo a
      functional transition from paracrine growth inhibitor to autocrine growth
      stimulator during progression of prostate cancer to the hormone-refractory
      phenotype.

PMID- 10068345
TI  - Saw palmetto extracts potently and noncompetitively inhibit human alpha1
      adrenoceptors in vitro.
AB  - BACKGROUND: We wanted to test whether phytotherapeutic agents used in the
      treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic
      properties in vitro. METHODS: Preparations of beta-sitosterol and extracts of
      stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several
      pharmaceutical companies. They were tested for their ability to inhibit
      [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin
      binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of
      phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was
      also investigated. RESULTS: Up to the highest concentration which could be
      tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin
      were without consistent inhibitory effect in all assays. In contrast, all tested
      saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors
      and agonist-induced [3H]inositol phosphate formation. Saturation binding
      experiments in the presence of a single saw palmetto extract concentration
      indicated a noncompetitive antagonism. The relationship between active
      concentrations in vitro and recommended therapeutic doses for the saw palmetto
      extracts was slightly lower than that for several chemically defined alpha1
      adrenoceptor antagonists. CONCLUSIONS: Saw palmetto extracts have alpha1
      adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic
      properties of these ingredients are similar to those of the chemically defined
      alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved
      in the therapeutic effects of these extracts in patients with lower urinary tract
      symptoms suggestive of benign prostatic obstruction.

PMID- 10068346
TI  - Influence of the alpha1-adrenergic antagonist, doxazosin, on noradrenaline
      induced modulation of cytoskeletal proteins in cultured hyperplastic prostatic
      stromal cells.
AB  - BACKGROUND: Doxazosin, an alpha1-adrenergic antagonist, inhibits sympathetic
      contraction of prostatic stromal smooth muscle cells and is used in the relief of
      obstructive benign prostatic hyperplasia (BPH). In vitro application of
      noradrenaline stimulates expression of cytoskeletal filaments, particularly actin
      and myosin, by prostatic stromal cells, thus enhancing their differentiation
      towards smooth muscle cells. This study examined the possible role of doxazosin
      in reversing this phenotypic modulation as well as in inhibiting smooth muscle
      cell contraction. METHODS: Stromal cell tissue cultures derived from 10 human
      hyperplastic prostates were rendered quiescent by reduction of stripped fetal
      calf serum (FCS) to 1% (v/v) in the medium followed by treatment with 20 microM
      noradrenaline and/or 1 microM doxazosin for 10 days. Doxazosin, in 10-fold
      increments of concentration, was also added, separately, to two of these cell
      cultures, which were either quiescent or growing in 10% normal (unstripped) FCS.
      Harvested cells were labelled with fluorescein-labelled antisera to smooth muscle
      cytoskeletal filaments, and their individual fluorescence levels were analyzed
      flow-cytometrically. RESULTS: Noradrenaline increased expression of all
      cytoskeletal filaments studied. This effect was greatest for actin and myosin in
      proliferating cell cultures. Doxazosin largely reversed the increase in filament
      expression. This effect was most significant for actin and myosin and greatest in
      quiescent cultures. However, inhibition of the agonist effect of noradrenaline by
      doxazosin showed no clear dose-related response, in that expression of
      cytoskeletal filaments was differentially inhibited. CONCLUSIONS: The data
      suggest that doxazosin may inhibit not only stromal contraction of differentiated
      smooth muscle cells in BPH but also the phenotypic modulation of stromal smooth
      muscle cell differentiation induced by noradrenaline. These actions, together,
      may render prostatic stroma less contractile, and hence less able to respond to
      sympathetic stimulation, in patients with BPH. While effects on isolated stromal
      cells are of undoubted importance, failure to demonstrate a consistent dose
      response relationship between expression of smooth muscle cell phenotype and
      inhibition by doxazosin suggests that additional influences, including humoral
      factors as well as the proximity of differentiated epithelium, are also likely to
      be involved in this interaction in the intact tissue.

PMID- 10068347
TI  - Synthetic retinoid CD437 induces S-phase arrest and apoptosis in human prostate
      cancer cells LNCaP and PC-3.
AB  - BACKGROUND: Exposure of prostate carcinoma cell lines to retinoids, which
      function through the classical retinoic acid nuclear receptor, (RARs) or retinoid
      X receptors (RXRs), results in minimal cytostatic inhibition of cell
      proliferation. METHODS: Growth inhibition and various regulatory responses were
      investigated in two human prostate carcinoma cell lines (LNCaP and PC-3) treated
      with or without a synthetic retinoid, CD 437. RESULTS: Incubation of prostate
      carcinoma cell lines with a novel retinoid CD437 resulted in the marked
      inhibition of proliferation. LNCaP and PC-3 possessed IC50 values for CD437 of
      375 nM and 550 nM, respectively. Incubation with 1 microM CD437 for 24 hr
      resulted in 100% and 60% inhibition of growth in LNCaP and PC-3 cells,
      respectively. Simultaneously, cell flow cytometric analyses revealed a dramatic
      increase of the cell population in S phase, in both LNCaP (from 38.6% up to
      86.7%) and PC-3 (27.9% to 55.7%), and a decreased proportion of cells in G2
      phase, in LNCaP (from 23.7% down to 1.2%) and PC-3 (14.9% to 2.2%), indicating a
      significant S-phase arrest. The cell growth inhibition and S-phase arrest in
      these cells were followed by apoptosis, as revealed by the acquisition of the
      characteristic cell morphology including the appearance of apoptotic bodies, and
      further confirmed by cellular DNA fragmentation. CD437-induced-S phase arrest was
      associated with upregulated mRNA levels of p21waf1/cip1/sdi1 in both LNCaP
      (p53+/+) and PC-3 (53-/-) cells. CONCLUSIONS: CD437 represents a unique retinoid
      that induces S-phase arrest and apoptosis in both androgen-dependent (LNCaP) and 
      independent (PC-3) human prostate cancer cells, suggesting a potential role of
      CD437 in the treatment of human prostate cancer.

PMID- 10068348
TI  - Citrate in the diagnosis of prostate cancer.
AB  - BACKGROUND: One of the major current problems involved in prostate cancer (PCa)
      is the unavailability of sensitive, accurate, and preferably noninvasive
      procedures for the diagnosis of PCa. Moreover, procedures are needed which will
      permit the early detection, staging, location, and estimation of the volume of
      malignancy, and preferably a mapping of the prostate for follow-up of progression
      and regression of the malignancy. METHODS: The unique citrate relationships of
      the prostate, coupled with recent developments and technological advancements in
      magnetic resonance spectroscopy (MRS) for the in situ determination of citrate
      levels, now provides an excellent diagnostic procedure which can achieve all
      these goals. There exist strong, compelling basic and clinical studies in support
      of the employment of 1H MRS measurements of citrate and other associated
      metabolites in the diagnosis of PCa. RESULTS: This review provides the background
      leading to the current status of MRS citrate analysis, summarizes the data from
      clinical trials, and describes the applications of the procedure for the
      diagnosis of PCa and follow-up of patients. The use of MRS studies in defining
      the functional, as well as pathological relationships of the prostate, is also
      discussed. CONCLUSIONS: This review is intended to be informative to the prostate
      and oncology-interested community, and, hopefully, to engender much-needed
      interest and support in future research regarding the prostate relationships
      described in this report.

PMID- 10068349
TI  - Abstracts from the 1998 International Symposium on Biology of Prostate Growth.
      Bethesda, Maryland, USA. March 15-18, 1998.

PMID- 10068350
TI  - [Complications in two children with acute lymphatic leukemia caused by
      vaccination against varicella zoster virus].
AB  - Complications in two varicella zoster virus (VZV) vaccinated children with
      leukemia in remission are reported. Case I presented with varicella on day 30
      after vaccination, with a relapse on day 49 and development of zoster on day 70.
      VZV was detected in vesicles by PCR on days 49 and 70. Case II presented with
      varicella on day 32 after vaccination, and VZV was detected in vesicles and nasal
      secretion. The manifestations were mild and responded to treatment. PCR methods
      were directed toward the R5 and PS regions. The virus from the two children was
      unambiguously identified as the Oka vaccine strain. The majority of Danish field
      strains had only one copy of the 112 basepair repeat element in the R5 region,
      but two, four and presumably higher copy numbers were also seen. All Danish field
      strains had the Pst1 cleavage site in the PS region.

PMID- 10068351
TI  - [The role of echotomography in minor renal traumatology].
AB  - We examined retrospectively the records of 108 patients with blunt renal trauma
      to determine the importance of echography as radiological investigations in minor
      renal trauma. Of patients 62 (66.6%) had a minor renal injuries, 21 (22.5%) had a
      moderate injuries and 10 (10.7%) had a major renal renal injuries. All patients
      who had microscopic hematuria without shock or other associated injuries had
      minor injuries. Echography and excretory urogram (IVP) confirmed the injuries
      except in 5 cases who presenting with only gross hematuria and the IVP don't
      confirmed the presence of a subcapsular hematoma identified by echography.
      Echography was more sensitive and specific than an IVP in minor renal trauma.
      Radiological investigations are not needed in those with microscopic hematuria
      and no shock or associated injuries, however we prefer performing ever an
      echography for medical and legal risk because a microscopic hematuria may include
      a neoplasm or other lesions.

PMID- 10068352
TI  - ACSM/AHA Release Recommendations for fitness facilities. American College of
      Sports Medicine / American Heart Association.

PMID- 10068353
TI  - American College of Chest Physicians issues consensus statement on the management
      of cough.

PMID- 10068354
TI  - The Tecota Inhaler.

PMID- 10068355
TI  - Australian and New Zealand College of Anaesthetists and Faculty of Intensive Care
      annual scientific meeting. Newcastle, NSW, May 2-6, 1998. Abstracts.

PMID- 10068356
TI  - Medical therapy after successful percutaneous coronary revascularization.
AB  - BACKGROUND: Percutaneous coronary revascularization frequently relieves angina in
      patients with ischemic heart disease and may obviate the need for antianginal
      medications. OBJECTIVE: To examine the use of antianginal medications after
      successful percutaneous coronary revascularization. DESIGN: Retrospective cohort
      study of the Mayo Clinic PTCA [percutaneous transluminal coronary angioplasty]
      Registry. SETTING: Tertiary care center. PATIENTS: 3831 patients who underwent
      successful percutaneous coronary revascularization from September 1979 through
      August 1997 and had not had myocardial infarction within the year before the
      intervention. MEASUREMENTS: Use of antianginal medications (beta-adrenergic
      blockers, nitrates, and calcium-channel blockers) before the intervention, at
      hospital discharge, and 6 months after the intervention. RESULTS: 99% of patients
      reported improvement in their symptoms at hospital discharge. At 6 months, 87% of
      patients were free of myocardial infarction, coronary bypass surgery, or
      additional percutaneous intervention. Compared with 66% of patients before the
      index intervention, only 12% of patients had severe angina at 6 months and 69%
      were completely free of angina. Nonetheless, at 6 months, 39% of patients were
      receiving beta-adrenergic blockers (preprocedure proportion, 43%; P < 0.001), 36%
      were receiving nitrates (preprocedure proportion, 41%; P < 0.001), and 57% were
      receiving calcium-channel blockers (preprocedure proportion, 50%; P < 0.001).
      These trends persisted for patients without hypertension and those who had
      complete revascularization. CONCLUSIONS: Successful percutaneous coronary
      revascularization did not substantially supplant the use of antianginal
      medications, which were commonly used despite the marked improvement in anginal
      status. This may reflect reluctance to alter therapy once symptoms of angina
      subside. Guidelines on continued medical therapy after percutaneous coronary
      revascularization are needed.

PMID- 10068357
TI  - Patient age and decisions to withhold life-sustaining treatments from seriously
      ill, hospitalized adults. SUPPORT Investigators. Study to Understand Prognoses
      and Preferences for Outcomes and Risks of Treatment.
AB  - BACKGROUND: Patient age may influence decisions to withhold life-sustaining
      treatments, independent of patients' preferences for or ability to benefit from
      such treatments. Controversy exists about the appropriateness of using age as a
      criterion for making treatment decisions. OBJECTIVE: To determine the effect of
      age on decisions to withhold life-sustaining therapies. DESIGN: Prospective
      cohort study. SETTING: Five medical centers participating in the Study to
      Understand Prognoses and Preferences for Outcomes and Risks of Treatments
      (SUPPORT). PATIENTS: 9105 hospitalized adults who had one of nine illnesses
      associated with an average 6-month mortality rate of 50%. MEASUREMENTS: Outcomes
      were the presence and timing of decisions to withhold ventilator support,
      surgery, and dialysis. Adjustment was made for sociodemographic characteristics,
      prognoses, baseline function, patients' preferences for life-extending care, and
      physicians' understanding of patients' preferences for life-extending care.
      RESULTS: The median patient age was 63 years; 44% of patients were women, and 53%
      survived to 180 days. In adjusted analyses, older age was associated with higher
      rates of withholding each of the three life-sustaining treatments studied. For
      ventilator support, the rate of decisions to withhold therapy increased 15% with
      each decade of age (hazard ratio, 1.15 [95% CI, 1.12 to 1.19]); for surgery, the
      increase per decade was 19% (hazard ratio, 1.19 [CI, 1.12 to 1.27]); and for
      dialysis, the increase per decade was 12% (hazard ratio, 1.12 [CI, 1.06 to
      1.19]). Physicians underestimated older patients' preferences for life-extending
      care; adjustment for this underestimation resulted in an attenuation of the
      association between age and decisions to withhold treatments. CONCLUSION: Even
      after adjustment for differences in patients' prognoses and preferences, older
      age was associated with higher rates of decisions to withhold ventilator support,
      surgery, and dialysis.

PMID- 10068358
TI  - Compliance with handwashing in a teaching hospital. Infection Control Program.
AB  - BACKGROUND: Transmission of microorganisms from the hands of health care workers
      is the main source of cross-infection in hospitals and can be prevented by
      handwashing. OBJECTIVE: To identify predictors of noncompliance with handwashing
      during routine patient care. DESIGN: Observational study. SETTING: Teaching
      hospital in Geneva, Switzerland. PARTICIPANTS: Nurses (66%), physicians (10%),
      nursing assistants (13%), and other health care workers (11%). MEASUREMENTS:
      Compliance with handwashing. RESULTS: In 2834 observed opportunities for
      handwashing, average compliance was 48%. In multivariate analysis, noncompliance
      was higher among physicians (odds ratio [OR], 2.8 [95% CI, 1.9 to 4.1]), nursing
      assistants (OR, 1.3 [CI, 1.0 to 1.6]), and other health care workers (OR, 2.1
      [CI, 1.4 to 3.2]) than among nurses and was lowest on weekends (OR, 0.6 [CI, 0.4
      to 0.8]). Noncompliance was higher in intensive care than in internal medicine
      units (OR, 2.0 [CI, 1.3 to 3.1]), during procedures that carry a high risk for
      contamination (OR, 1.8 [CI, 1.4 to 2.4]), and when intensity of patient care was
      high (compared with < or = 20 opportunities for handwashing per hour of care, 21
      to 40 opportunities: OR, 1.3 [CI, 1.0 to 1.7]; 41 to 60 opportunities: OR, 2.1
      [CI, 1.5 to 2.9]; and > 60 opportunities: OR, 2.1 [CI, 1.3 to 3.5]). CONCLUSIONS:
      Compliance with handwashing was moderate. Variation across hospital ward and type
      of health care worker suggests that targeted educational programs may be useful.
      Even though observational data cannot prove causality, the association between
      noncompliance and intensity of care suggests that understaffing may decrease
      quality of patient care.

PMID- 10068359
TI  - Epidemiologic and molecular investigation of outbreaks of hepatitis C virus
      infection on a pediatric oncology service.
AB  - BACKGROUND: Despite screening of blood donors, hepatitis C virus (HCV) infection
      can occur in patients who receive multiple transfusions. OBJECTIVE: To clarify
      mechanisms of nosocomial transmission of HCV. DESIGN: Epidemiologic and molecular
      analyses of hepatitis C outbreaks. SETTING: Pediatric oncology ward. PATIENTS:
      Children with cancer. MEASUREMENTS: Epidemiologic analysis, HCV RNA detection,
      genotyping, and hypervariable region 1 (HVR1) sequencing. RESULTS: Ten cases of
      infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing
      of HVR1 revealed three related strains. Despite an overhaul of hygiene
      procedures, a patient infected with genotype 1b generated nine subsequent
      infected patients in 1994. Several patients had high virus titers and strongly
      delayed anti-HCV antibody responses. All had permanent intravenous catheters.
      Multidose vials used for flushing or treatment had probably been contaminated
      during periods of overlapping treatment. CONCLUSIONS: Contamination of multidose
      vials was the most likely mode of HCV transmission; therefore, use of such vials
      should be restricted. Rigorous adherence to hygiene routines remains essential to
      preventing transmission of bloodborne infections.

PMID- 10068360
TI  - Update in rheumatology.

PMID- 10068361
TI  - A shared statement of ethical principles for those who shape and give health
      care: a working draft from the Tavistock group.
AB  - Health care delivery in many countries has expanded over the past 150 years from
      a largely social service delivered by individual practitioners to an intricate
      network of services provided by teams of professionals. The problems of
      increasing resource consumption, financial constraints, complexity, and poor
      system design that have emerged as consequences of these changes have exacerbated
      many of the ethical tensions inherent in health care and have created new ones.
      Many groups of professionals that give and affect health care have established
      separate codes of ethics for their own disciplines, but no shared code exists
      that might bring all stakeholders in health care into a more consistent moral
      framework. A multidisciplinary group therefore recently met at Tavistock Square
      in London in an effort to prepare such a shared code. The result was not a code
      but a more basic and generic statement of ethical principles. The intent and hope
      is that it will offer clear guidance for tough calls in real world settings. It
      is presented here not as a finished work, but as a draft to elicit comment,
      critique, suggestions for revision, and, especially, ideas for implementation.

PMID- 10068362
TI  - The trouble with families: toward an ethic of accommodation.
AB  - Although some clinicians are extraordinarily sensitive to the legitimate roles of
      patients' families in medical crises, a persistent tendency to equate families
      with trouble is evident in both the literature and the practice of medicine. Some
      negative presumptions about families derive from western medicine's almost
      exclusive focus on the individual patient in codes of ethics, training, and
      practice. Modern bioethics has reinforced this individualistic approach.
      Physicians' primary responsibilities are unequivocally to their patients, but a
      complete understanding of the patient's personhood must include consideration of
      the significant persons who help define the patient's core identity. One source
      of tension between professionals and families lies in differing perceptions of
      the roles that family members should play and how they should play them. Members
      of a family may act as advocates, provide or manage care, serve as trusted
      companions on the journey through illness and death, and make decisions on behalf
      of an incompetent patient. Each role presents potential conflicts. Other sources
      of conflict include disagreement within a family; challenges to physician
      authority; fear of litigation; and differing religious, ethnic, or cultural
      traditions. An ethic of accommodation emphasizes the need to negotiate care plans
      that do not compromise patients' basic interests but that recognize the
      capacities and limitations of family members. Family caregivers want
      understandable and timely information, better training, compassionate recognition
      of their anxiety, guidance in defining their roles and responsibilities, and
      support for the setting of fair limits on their sacrifices. Health care
      professionals can better meet these needs through education and skills
      acquisition, the establishment of partnerships with families, and regular
      dialogue and communication.

PMID- 10068363
TI  - It is time for action: improving hand hygiene in hospitals.

PMID- 10068364
TI  - A novel antimicrobial agent joins the battle against resistant bacteria.

PMID- 10068365
TI  - A simple procedure: a play in one act.

PMID- 10068366
TI  - Screening for thyroid disease.

PMID- 10068367
TI  - Screening for thyroid disease.

PMID- 10068368
TI  - Screening for thyroid disease.

PMID- 10068369
TI  - Screening for thyroid disease.

PMID- 10068370
TI  - Impaired glucose tolerance in HIV-positive patients receiving and those not
      receiving protease inhibitors.

PMID- 10068371
TI  - Thrombotic thrombocytopenic purpura after Ecstasy-induced acute liver failure.

PMID- 10068372
TI  - Severe hepatotoxicity associated with troglitazone.

PMID- 10068373
TI  - Current health care environment.

PMID- 10068374
TI  - Current health care environment.

PMID- 10068375
TI  - Current health care environment.

PMID- 10068376
TI  - Doing everything.

PMID- 10068377
TI  - Preservation of the chief medical residency.

PMID- 10068378
TI  - Solid organ transplantation. 2: Ethical considerations.

PMID- 10068379
TI  - Ideas and trends: medical informatics and health care computing.

PMID- 10068380
TI  - The association between cardiorespiratory fitness and impaired fasting glucose
      and type 2 diabetes mellitus in men.
AB  - BACKGROUND: Several studies show an inverse association between self-reported
      physical activity and type 2 diabetes. It is not known whether physical activity
      or cardiorespiratory fitness is associated with the onset of objectively
      determined impaired fasting glucose and type 2 diabetes. OBJECTIVE: To determine
      whether cardiorespiratory fitness, an objective marker of physical activity, is
      associated with risk for impaired fasting glucose and type 2 diabetes. DESIGN:
      Population-based prospective study. SETTING: Preventive medicine clinic.
      PATIENTS: 8633 nondiabetic men (of whom 7511 did not have impaired fasting
      glucose) who were examined at least twice. MEASUREMENTS: Cardiorespiratory
      fitness (determined by a maximal exercise test on a treadmill), fasting plasma
      glucose level, and other clinical and personal characteristics and incidence of
      impaired fasting glucose and type 2 diabetes. RESULTS: During an average follow
      up of 6 years, 149 patients developed type 2 diabetes and 593 patients developed
      impaired fasting glucose. After age, cigarette smoking, alcohol consumption, and
      parental diabetes were considered, men in the low-fitness group (the least fit
      20% of the cohort) at baseline had a 1.9-fold risk (95% CI, 1.5- to 2.4-fold) for
      impaired fasting glucose and a 3.7-fold risk (CI, 2.4- to 5.8-fold) for diabetes
      compared with those in the high-fitness group (the most fit 40% of the cohort).
      The risk for impaired fasting glucose was elevated in older men and those with a
      higher body mass index. Age, body mass index, blood pressure, triglyceride level,
      and a history of parental diabetes were also directly related to risk for type 2
      diabetes. CONCLUSIONS: Low cardiorespiratory fitness was associated with
      increased risk for impaired fasting glucose and type 2 diabetes. A sedentary
      lifestyle may contribute to the progression from normal fasting glucose to
      impaired fasting glucose and diabetes. Risk for type 2 diabetes was elevated in
      older persons and those with higher body mass index, blood pressure, and
      triglyceride levels and a parental history of diabetes.

PMID- 10068381
TI  - The costs, clinical benefits, and cost-effectiveness of screening for cervical
      cancer in HIV-infected women.
AB  - BACKGROUND: Women with HIV infection have a higher risk for cervical squamous
      intraepithelial lesions than do women without HIV infection, and the optimal
      regimen for cervical cancer screening in these women is uncertain. OBJECTIVE: To
      assess the net health consequences, costs, and cost-effectiveness of various
      screening strategies for cervical neoplasia and cancer in HIV-infected women.
      DESIGN: A cost-effectiveness analysis from a societal perspective done by using a
      state-transition Markov model. Values for incidence, progression, and regression
      of cervical neoplasia; efficacy of screening and treatment; progression of HIV
      disease; mortality from HIV infection and cancer; quality of life; and costs were
      obtained from the literature. SETTING: Simulated clinical practice in the United
      States. PATIENTS: HIV-infected women representative of the U.S. population.
      INTERVENTION: Six main screening strategies--no screening, annual Papanicolaou
      smears, annual Papanicolaou smears after two negative smears obtained 6 months
      apart (recommended by the Centers for Disease Control and Prevention), semiannual
      Papanicolaou smears, annual colposcopy, and semiannual colposcopy--were
      considered. MEASUREMENTS: Quality-adjusted life-years (QALYs), lifetime costs,
      and incremental cost-effectiveness. RESULTS: Annual Papanicolaou smear screening
      resulted in a 2.1-month gain in quality-adjusted life expectancy for an
      incremental cost of $12,800 per QALY saved. Annual Papanicolaou smear screening
      after two negative smears obtained 6 months apart provided an additional 0.04
      QALYs at a cost of $14,800 per QALY saved. Semiannual Papanicolaou smear
      screening provided a further 0.17 QALYs at a cost of $27,600 per QALY saved.
      Annual colposcopy cost more but provided no additional benefit compared with that
      given by semiannual Papanicolaou smear screening, and semiannual colposcopy
      exceeded $375,000 per QALY saved. Results were most sensitive to the rate of
      progression of neoplasia to invasive cancer. CONCLUSIONS: In HIV-infected women,
      cervical cancer screening with annual Papanicolaou smears after two negative
      smears obtained 6 months apart offers quality-adjusted life expectancy benefits
      at a cost comparable to that of other clinical preventive interventions.

PMID- 10068382
TI  - Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing
      olestra or triglycerides. A 6-week randomized, placebo-controlled trial.
AB  - BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is
      not absorbed, it may cause digestive symptoms when consumed in large amounts.
      OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in
      adults and children who freely consume snacks containing olestra or regular
      snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo
      controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to
      89 years of age. INTERVENTION: Households received identical packages labeled as
      containing olestra corn or potato chips. These packages contained either olestra
      or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their
      impact on daily activities were reported in a daily record. RESULTS: At least one
      gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the
      olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points
      [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did
      not differ significantly in the proportion of participants who reported
      individual gastrointestinal symptoms; however, more controls reported nausea
      (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4
      percentage points]; P = 0.02). The only difference between groups for the mean
      numbers of days on which symptoms were reported was that participants in the
      olestra group had 1 more symptom-day of more frequent bowel movements than did
      controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9
      symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ
      in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful
      or bothersome gastrointestinal effects are not associated with unregulated
      consumption of olestra corn and potato chips in the home.

PMID- 10068383
TI  - Effects of estrogen and estrogen-progestin on mammographic parenchymal density.
      Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators.
AB  - BACKGROUND: In longitudinal studies, greater mammographic density is associated
      with an increased risk for breast cancer. OBJECTIVE: To assess differences
      between placebo, estrogen, and three estrogen-progestin regimens on change in
      mammographic density. DESIGN: Subset analysis of a 3-year, multicenter, double
      blind, randomized, placebo-controlled trial. SETTING: Seven ambulatory study
      centers. PARTICIPANTS: 307 of the 875 women in the Postmenopausal
      Estrogen/Progestin Interventions Trial. Participants had a baseline mammogram and
      at least one follow-up mammogram available, adhered to treatment, had not taken
      estrogen for at least 5 years before baseline, and did not have breast implants.
      INTERVENTION: Treatments were placebo, conjugated equine estrogens (CEE), CEE
      plus cyclic medroxyprogesterone acetate (MPA), CEE plus daily MPA, and CEE plus
      cyclic micronized progesterone (MP). MEASUREMENTS: Change in radiographic density
      (according to American College of Radiology Breast Imaging Reporting and Data
      System grades) on mammography. RESULTS: Almost all increases in mammographic
      density occurred within the first year. At 12 months, the percentage of women
      with density grade increases was 0% (95% CI, 0.0% to 4.6%) in the placebo group,
      3.5% (CI, 1.0% to 12.0%) in the CEE group, 23.5% (CI, 11.9% to 35.1%) in the CEE
      plus cyclic MPA group, 19.4% (CI, 9.9% to 28.9%) in the CEE plus daily MPA group,
      and 16.4% (CI, 6.6% to 26.2%) in the CEE plus cyclic MP group. At 12 months, the
      odds of an increase in mammographic density were 13.1 (95% CI, 2.4 to 73.3) with
      CEE plus cyclic MPA, 9.0 (CI, 1.6 to 50.1) with CEE plus daily MPA, and 7.2 (CI,
      1.3 to 40.0) with CEE plus cyclic micronized progesterone compared with CEE
      alone. CONCLUSIONS: Further study of the magnitude and meaning of increased
      mammographic density due to use of estrogen and estrogen-progestins is warranted
      because mammographic density may be a marker for risk for breast cancer.

PMID- 10068384
TI  - Elevated serum estradiol and testosterone concentrations are associated with a
      high risk for breast cancer. Study of Osteoporotic Fractures Research Group.
AB  - BACKGROUND: The relation between endogenous steroid hormones and risk for breast
      cancer is uncertain. Measurement of sex hormone levels may identify women at high
      risk for breast cancer who should consider preventive therapies. OBJECTIVE: To
      test the hypothesis that serum concentrations of estradiol and testosterone
      predict risk for breast cancer. DESIGN: Prospective case-cohort study. SETTING:
      Four clinical centers in the United States. PARTICIPANTS: 97 women with confirmed
      incident breast cancer and 244 randomly selected controls; all women were white,
      65 years of age or older, and were not receiving estrogen. MEASUREMENTS: Sex
      steroid hormone concentrations were assayed by using serum that was collected at
      baseline and stored at -190 degrees C. Risk factors for breast cancer were
      ascertained by questionnaire. Incident cases of breast cancer were confirmed by
      review of medical records during an average period of 3.2 years. RESULTS: The
      relative risk for breast cancer in women with the highest concentration of
      bioavailable estradiol (> or = 6.83 pmol/L or 1.9 pg/mL) was 3.6 (95% CI, 1.3 to
      10.0) compared with women with the lowest concentration. The risk for breast
      cancer in women with the highest concentration of free testosterone compared with
      those with the lowest concentration was 3.3 (CI, 1.1 to 10.3). The estimated
      incidence of breast cancer per 1000 person-years was 0.4 (CI, 0.0 to 1.3) in
      women with the lowest levels of bioavailable estradiol and free testosterone
      compared with 6.5 (CI, 2.7 to 10.3) in women with the highest concentrations of
      these hormones. Traditional risk factors for breast cancer were similar in case
      patients and controls. Adjustments for these risk factors had little effect on
      the results. CONCLUSIONS: Estradiol and testosterone levels may play important
      roles in the development of breast cancer in older women. A single measurement of
      bioavailable estradiol and free testosterone may be used to estimate a woman's
      risk for breast cancer. Women identified as being at high risk for breast cancer
      as determined by these hormone levels may benefit from antiestrogen treatment for
      primary prevention.

PMID- 10068385
TI  - Birthweight and the risk for type 2 diabetes mellitus in adult women.
AB  - BACKGROUND: Previous reports have suggested an association between birthweight
      and type 2 diabetes mellitus. OBJECTIVE: To investigate the association between
      birthweight and type 2 diabetes in a large cohort of adult women, taking into
      account potential explanatory factors in childhood and adult life. DESIGN: Cohort
      study. Birthweight was ascertained at the end of follow-up. SETTING: The Nurses'
      Health Study, a cohort of 121,701 U.S. women born from 1921 to 1946 who have been
      followed since 1976. PARTICIPANTS: 69,526 women in the Nurses' Health Study who
      were free of diabetes at baseline and reported their own birthweight on the 1992
      questionnaire. MEASUREMENT: 2123 cases of confirmed type 2 diabetes diagnosed
      from 1976 to 1992. RESULTS: Low birthweight was associated with increased risk
      for type 2 diabetes. Age-adjusted relative risks suggested a reverse J-shape
      association between birthweight and risk for type 2 diabetes. However, after
      adjustment for adult body mass index and maternal history of diabetes, an inverse
      association across the entire range of birthweight became apparent; compared with
      the reference group, relative risks by ascending birthweight category were 1.83
      (95% CI, 1.55 to 2.16) for birthweight less than 5.0 lb, 1.76 (CI, 1.49 to 2.07)
      for birthweight 5.0 to 5.5 lb, 1.23 (CI, 1.11 to 1.37) for birthweight 5.6 to 7.0
      lb, 0.95 (CI, 0.82 to 1.10) for birthweight 8.6 to 10.0 lb, and 0.83 (CI, 0.63 to
      1.07) for birthweight of more than 10 lb (P for trend < 0.001). Adjustment for
      ethnicity, childhood socioeconomic status, and adult lifestyle factors did not
      substantially alter this association. The association between birthweight and
      risk for type 2 diabetes was strongest among women whose mothers had no history
      of diabetes. CONCLUSIONS: Birthweight is inversely associated with risk for type
      2 diabetes during adulthood. Examination of prenatal nutrition and other
      potential in utero determinants of both birthweight and risk for type 2 diabetes
      may yield new means to prevent type 2 diabetes.

PMID- 10068386
TI  - Nefazodone-induced liver failure: report of three cases.
AB  - BACKGROUND: Liver failure is a rare but devastating result of drug toxicity.
      OBJECTIVE: To describe three cases of subfulminant liver failure that were
      probably caused by nefazodone, a new antidepressant that is a synthetically
      derived phenylpiperazine. DESIGN: Case series. SETTING: Two university medical
      centers and a children's hospital. PATIENTS: Three women 16 to 57 years of age.
      INTERVENTION: Two patients underwent liver transplantation; the third was listed
      for transplantation but subsequently improved. MEASUREMENT: Liver biopsy.
      RESULTS: Nefazodone was administered for 14 to 28 weeks before the onset of
      symptoms. The duration of jaundice before onset of encephalopathy ranged from 4
      to 6 weeks. All cases of liver failure had similar histologic appearance, with
      prominent necrosis in the centrolobular areas (zone 3). One patient had
      successful liver transplantation, one underwent transplantation but died, and one
      improved without transplantation. The temporal onset of disease after the start
      of nefazodone therapy suggested severe hepatocellular injury caused by the drug.
      CONCLUSIONS: Because nefazodone seems to cause severe hepatocellular injury in an
      idiosyncratic manner, routine liver chemistries should be performed before
      starting nefazodone therapy and patients should be monitored regularly. Therapy
      should be discontinued if liver enzyme concentrations become abnormal.

PMID- 10068387
TI  - Association between the Epworth sleepiness scale and the multiple sleep latency
      test in a clinical population.
AB  - BACKGROUND: Excessive daytime sleepiness can be evaluated with both subjective
      and objective tests. OBJECTIVE: To examine the association between Epworth
      Sleepiness Scale scores and sleep latency on the multiple sleep latency test.
      DESIGN: Case series. SETTING: Referral sleep disorders center. PATIENTS: 102
      consecutive patients evaluated for excessive daytime sleepiness. MEASUREMENTS:
      Epworth Sleepiness Scale scores and mean sleep latency on the multiple sleep
      latency test. RESULTS: No significant association was seen between Epworth scores
      and mean sleep latency (Pearson correlation, -0.17 [95% CI, -0.35 to 0.03]; P =
      0.09) (analysis of variance, P = 0.13). The mean Epworth score did not differ in
      three groups of patients who were defined by mean sleep latency as having normal
      sleep latency (>10 minutes), moderate sleep latency (5 to 10 minutes), or severe
      sleep latency (<5 minutes) (analysis of variance, P = 0.13). CONCLUSIONS: No
      statistically or clinically significant association was seen between Epworth
      scores and mean sleep latency. The subjective Epworth Sleepiness Scale and the
      objective multiple sleep latency test may evaluate different, complementary
      aspects of sleepiness.

PMID- 10068388
TI  - Coccidioidomycosis: a regional disease of national importance. Rethinking
      approaches for control.
AB  - Coccidioidomycosis is an increasingly important health problem because of the
      migration of large numbers of persons to portions of the southwestern United
      States in which the disease is endemic and because of the increasing numbers of
      immunosuppressed patients. Most infections due to Coccidioides immitis, although
      causing significant illness, are self-limited and resolve over a period of weeks
      to months without specific treatment. It is not known whether antifungal
      treatment of early infections hastens resolution of the primary illness or
      prevents complications. Even so, diagnosis of early infections is of value for
      allaying patient anxiety, lessening the need for further diagnostic studies,
      decreasing empirical use of antibacterial agents, and facilitating early
      identification of patients with complications that are more serious. Patients who
      develop chronic coccidioidal pneumonia or extrapulmonary infection often have
      complicated courses that require the involvement of various medical, surgical,
      and radiologic subspecialties for management. Improvement of the ability to
      control the problem of coccidioidomycosis will require research into the
      molecular and cellular biology of C. immitis, vaccine development to prevent
      coccidioidal infection, a better understanding of the soil ecology that supports
      the fungus in its endemic regions, and discovery of new antifungal drugs. In
      addition, government agencies, colleges, the military, and employers could
      improve public health by initiating education programs about the most common
      manifestations of the disease among persons at risk for infection.

PMID- 10068389
TI  - Biliary sludge.
AB  - Biliary sludge was first described with the advent of ultrasonography in the
      1970s. It is defined as a mixture of particulate matter and bile that occurs when
      solutes in bile precipitate. Its composition varies, but cholesterol monohydrate
      crystals, calcium bilirubinate, and other calcium salts are the most common
      components. The clinical course of biliary sludge varies, and complete
      resolution, a waxing and waning course, and progression to gallstones are all
      possible outcomes. Biliary sludge may cause complications, including biliary
      colic, acute pancreatitis, and acute cholecystitis. Clinical conditions and
      events associated with the formation of biliary sludge include rapid weight loss,
      pregnancy, ceftriaxone therapy, octreotide therapy, and bone marrow or solid
      organ transplantation. Sludge may be diagnosed on ultrasonography or bile
      microscopy, and the optimal diagnostic method depends on the clinical setting.
      This paper proposes a protocol for the microscopic diagnosis of sludge. There are
      no proven methods for the prevention of sludge formation, even in high-risk
      patients, and patients should not be routinely monitored for the development of
      sludge. Asymptomatic patients with sludge can be managed expectantly. If patients
      with sludge develop symptoms or complications, cholecystectomy should be
      considered as the definitive therapy. Further studies of the pathogenesis,
      natural history, and clinical associations of biliary sludge will be essential to
      our understanding of gallstones and other biliary tract abnormalities.

PMID- 10068390
TI  - When doctors marry doctors: a survey exploring the professional and family lives
      of young physicians.
AB  - BACKGROUND: Soon, half of all physicians may be married to other physicians (that
      is, in dual-doctor families). Little is known about how marriage to another
      physician affects physicians themselves. OBJECTIVE: To learn how physicians in
      dual-doctor families differ from other physicians in their professional and
      family lives and in their perceptions of career and family. DESIGN: Cross
      sectional survey. SETTING: Two medical schools in Ohio. PARTICIPANTS: A random
      sample of physicians from the classes of 1980 to 1990. MEASUREMENTS: Responses to
      a questionnaire on hours worked, income, number of children, child-rearing
      arrangements, and perceptions about work and family. RESULTS: Of 2000 eligible
      physicians, 1208 responded (752 men and 456 women). Twenty-two percent of male
      physicians and 44% of female physicians were married to physicians (P < 0.001).
      Men and women in dual-doctor families differed (P < 0.001) from other married
      physicians in key aspects of their professional and family lives: They earned
      less money, less often felt that their career took precedence over their spouse's
      career, and more often played a major role in child-rearing. These differences
      were greater for female physicians than for male physicians. Men and women in
      dual-doctor families were similar to other physicians in the frequency with which
      they achieved career goals and goals for their children and with which they felt
      conflict between professional and family roles. Marriage to another physician had
      distinct benefits (P < 0.001) for both men and women, including more frequent
      enjoyment from shared work interests and higher family incomes. CONCLUSIONS: Men
      and women in dual-doctor families differed from other physicians in many aspects
      of their professional and family lives, but they achieved their career and family
      goals as frequently. These differences reflect personal choices that will
      increasingly affect the profession as more physicians marry physicians.

PMID- 10068391
TI  - Fat, foreboding, and flatulence.

PMID- 10068392
TI  - The fetal origins of type 2 diabetes mellitus.

PMID- 10068393
TI  - The National Diabetes Education Program: changing the way diabetes is treated.

PMID- 10068394
TI  - The hospitalist movement in the United States: what does it mean for internists?

PMID- 10068395
TI  - Delayed hospital arrival for acute stroke.

PMID- 10068396
TI  - Breath tests for alcohol in gastroesophageal reflux disease.

PMID- 10068397
TI  - Hypocalcemia associated with alendronate.

PMID- 10068398
TI  - Leg ischemia in a patient receiving ritonavir and ergotamine.

PMID- 10068399
TI  - Troglitazone-associated hepatic failure.

PMID- 10068400
TI  - Illiteracy: the silent barrier to health care.

PMID- 10068401
TI  - Putting prevention into practice: the community's role.

PMID- 10068402
TI  - An introduction to the hospitalist model.
AB  - Motivated by a search for improved quality and efficiency, increasing numbers of
      hospitals and physicians are moving from systems in which all primary care
      providers manage their own hospitalized patients or rotate this responsibility
      among themselves at infrequent intervals to voluntary or mandatory systems in
      which patients are "handed off" to the care of an inpatient physician, the
      "hospitalist." All hospitalists manage medical patients in the hospital. Other
      potential roles for these physicians include triage in the emergency department,
      transfer of "out-of-network" patients, management of patients in the intensive
      care unit, preoperative and postoperative management of surgical patients, and
      leadership in hospital quality improvement and regulatory work. Hospitalists may
      add value by being more available to inpatients, having more hospital experience
      and expertise, and having an increased commitment to hospital quality improvement
      compared with primary care providers. Potential disadvantages of the hospitalist
      model include loss of information as a result of discontinuity of care, patient
      dissatisfaction, loss of acute care skills by primary care physicians, and
      burnout among hospitalists. A variety of models of care are needed to meet the
      clinical, organizational, financial, and political demands of diverse health care
      systems. The favored model should be that which produces the best clinical
      outcomes and the highest patient satisfaction at the lowest cost.

PMID- 10068403
TI  - Hospitalists and the practice of inpatient medicine: results of a survey of the
      National Association of Inpatient Physicians.
AB  - The number of hospital-based physicians, or hospitalists, in the United States
      has grown rapidly, yet no published data have characterized hospitalists or their
      practices. A self-administered questionnaire was used to describe 1) the features
      of hospitalists, 2) the hospitals in which they practice, and 3) the practice of
      inpatient medicine. The questionnaire contained 48 questions that covered four
      domains: demographic information about the respondent, the clinical and
      nonclinical workload and responsibilities of the respondent, organizational and
      financial aspects of the respondent's practice, and the respondent's satisfaction
      and his or her perception of the reaction of other physicians and nurses to the
      hospitalist system. The overall response rate was 57%. Data are reported on 372
      surveys. Respondents were young and most were men, and only 48% had practiced
      hospital-based medicine for more than 2 years. Eighty-nine percent of respondents
      were internists; of these, 51% were generalists and 38% were subspecialists. Most
      hospitalists limited their practices to the inpatient setting, but 37% practiced
      outpatient general internal medicine or subspecialty medicine in a limited
      capacity. In addition to providing care for inpatients, 90% of hospitalists were
      engaged in cohsultative medicine. Quality assurance and practice guideline
      development were the most frequently reported nonclinical activities (53% and
      46%; respectively). Small group practices (31%) and staff-model health
      maintenance organizations (25%) were the most common practice settings, and 78%
      of participants were reimbursed through salary. Financial incentives were common
      (43%) but modest. Accurate information about hospitalists and their practices
      will be important to clinicians, educators, researchers, and policymakers as the
      hospitalist movement continues to grow.

PMID- 10068404
TI  - The Park Nicollet experience in establishing a hospitalist system.
AB  - A hospitalist system was developed at Park Nicollet Clinic in 1993, was
      implemented in 1994, and remains in existence today. It was established without
      knowledge of any other similar program in the United States. Internists and
      family practitioners were given the choice to continue to care for hospitalized
      patients or to become totally office based. The new system has met with good
      patient acceptance along with increased physician satisfaction and retention.
      This paper describes some key aspects of the institution of the system in a
      multispecialty group that includes both family practitioners and internists.

PMID- 10068405
TI  - Implementation of a hospitalist system in a large health maintenance
      organization: the Kaiser Permanente experience.
AB  - This paper presents preliminary quality and utilization data from a hospitalist
      system that is being implemented at Kaiser Permanente, a large health maintenance
      organization with 16 hospitals in northern California. Hospitalist programs,
      which are staffed by clinicians highly skilled in caring for inpatients, are
      being launched with the aim of delivering high-quality, efficient medical care in
      an increasingly competitive health care delivery environment. This paper also
      describes, in some detail, the process of implementation at one hospital.
      Challenges to implementation included 1) overcoming the reluctance of clinic
      physicians to relinquish inpatient care responsibilities, 2) developing
      sustainable work schedules, 3) creating effective channels of communication
      between staff in inpatient and outpatient settings, and 4) designing appropriate
      compensation scales for hospitalists. Mean length of stay, patient-day rates,
      admission rates, consultation request rates, costs, and readmission rates were
      examined for patients discharged from adult medicine services at all 16 hospitals
      between 1 January 1994 and 30 June 1997. These preliminary resource utilization
      data seem promising, but further analysis is needed to assess how hospitalist
      programs may affect clinical quality of care, costs, and patient and provider
      satisfaction.

PMID- 10068406
TI  - An employer's perspective on hospitalists as a source of improved health care
      value.
AB  - The probable perspective of large employers toward the phenomenon of hospitalists
      can be derived by examining the four essential elements of health care value to
      employers. Current hospital care in the United States is thought to offer
      substantial opportunities for improvement, and the impact of hospitalist programs
      on an employer's sense of health care value is predicted to be favorable. This
      prediction, however, should be validated through outcomes research before it is
      widely propagated. If innovations as promising as hospitalist programs are to
      occur in ambulatory care, employers and other health care purchasers must be
      proactive in identifying and rewarding them.

PMID- 10068407
TI  - The impact of hospitalists on medical education and the academic health system.
AB  - Hospitalism as a career option is likely to reinforce the emphasis of traditional
      medical residency programs on inpatient care; may become an alternative area of
      emphasis in many subspecialty fellowship programs; and may even generate its own
      specific types of advanced training and certification. In the academic setting,
      subspecialists and their trainees are concerned that hospitalists may request
      fewer consultations, which could adversely affect subspecialists and the
      education of both fellows and residents. However, the focus and expertise of
      hospitalists is likely to improve inpatient education for students and residents
      and is appealing because it has the potential to improve the quality of inpatient
      care. Perhaps the major effect of the hospitalist movement on academic centers
      will be the creation of a cadre of physicians committed to critical pathways;
      clinical guidelines; quality assurance; risk management; clinical re-engineering;
      and the use of the inpatient service as a laboratory for developing, evaluating,
      and implementing initiatives to improve patient care. Although any fundamental
      change in the organization of clinical services brings with it the risk that
      essential components of the current system will be jeopardized, the hospitalist
      movement may have great benefits if it can develop safeguards to ensure seamless
      patient care and the appropriate use of subspecialty expertise.

PMID- 10068408
TI  - The hospitalist model: perspectives of the patient, the Internist, and internal
      medicine.
AB  - The use of hospitalists has implications for patients, for internists, and for
      the specialty of internal medicine. For patients, the greatest concern is
      interrupting the continuity of a supportive relationship with their regular
      physican. For many internists, the hospitalist model is attractive, but they are
      concerned that health plans will compel physicians to transfer their patients to
      a hospitalist at the time of admission to the hospital (mandatory hand-off).
      Thus, the hospitalist could become the means to exclude internists from hospital
      care and deprive them of an important source of professional satisfaction. The
      specialty of internal medicine is very concerned about the mandatory hand-off
      because it threatens the internist's identity as the physician who can care for
      the sickest patients in any venue, making it harder for patients and health plans
      to distinguish the internist from family physicians and nurse practitioners. The
      hospitalist movement has much to offer internal medicine. To enjoy the benefits
      and avoid the harms associated with the hospitalist model, internal medicine must
      resist the imposition of the mandatory hand-off and use the hospitalist's focus
      on excellent inpatient care to improve the practice of medicine by all
      internists.

PMID- 10068409
TI  - The hospitalist: a new medical specialty?
AB  - Economic forces have stimulated a growing role for physician "hospitalists" in
      caring for patients hospitalized by other physicians, and the question of whether
      hospital care constitutes a new medical specialty has been raised. Three recently
      recognized specialties--emergency medicine, family practice, and critical care-
      originated from trends in medical practice. All three fulfill the major criteria
      for a medical specialty: scientific legitimacy, the development of new training
      pathways, and the existence of academic departments. The hospitalist movement is
      currently underdeveloped in each of these areas. By training, most hospitalists
      are internists who are well prepared to care for inpatients. Internal medicine
      must determine how this new movement fits into the traditional framework of
      general internal medicine and medical subspecialties. Until it does, the future
      of inpatient medicine as a recognized specialty will remain uncertain.

PMID- 10068410
TI  - Evaluating the impact of hospitalists.
AB  - The hospital-based generalist physician is a recent organizational innovation in
      health care in the United States. Does the hospitalist model provide improved
      health care? The answer to this question lies in a rigorous evaluation of the
      hospitalist system in the clinical setting. This paper describes key outcomes
      that need to be assessed and methodologic issues that need to be addressed when
      conducting and interpreting the results of evaluations of the hospitalist model.
      To provide evidence about the value of the hospitalist model, quality of care
      should be evaluated through the measurement of both processes and outcomes. The
      clinical processes assessed may include diagnostic tests and treatments that are
      causally linked with outcomes. A variety of outcomes can be measured, such as
      death, clinical or physiologic status, physical function, and psychological well
      being. The analysis of resource use data can aid in an assessment of the relative
      costs and effectiveness of clinical services. An evaluation of the hospitalist
      model requires an adequate research design, which should include a precise
      definition of the model being studied, the selection of an appropriate comparison
      group, the collection of clinical and demographic information on patients, the
      specification of both process and outcome measures, and the use of statistical
      techniques that are appropriate to the questions being asked and the data being
      collected. The design must distinguish between outcomes attributable to the
      introduction of hospitalists and those attributable to other changes in medical
      treatments and the organization of care.

PMID- 10068411
TI  - The hospitalist: new boon for internal medicine or retreat from primary care?
AB  - The growing reliance on hospitalists in the United States has implications for
      several areas of internal medicine, including patient care, administration,
      clinical practice, and medical education. This paper discusses some of the
      potential advantages and disadvantages of the use of hospitalists in each of
      these areas. The new hospitalist practice mode highlights long-standing tensions
      about the role and direction of internal medicine, tensions that affect
      generalist and specialty care in both outpatient and hospital settings. The
      career trajectory of hospitalists will depend on whether burnout is a problem and
      on whether hospitalists will be able to compete effectively with sub-specialists,
      such as cardiologists and physicians specializing in AIDS. Clearly, hospitalism
      meets a clinical need and expands opportunities for internists, but it is
      important that it not overreach, forfeiting primary care turf and distorting
      medical education. This new field warrants close monitoring because of its
      potential effects and because-unlike related fields, such as emergency medicine
      and intensive care--its birth was strongly influenced by system-wide financial
      considerations.

PMID- 10068412
TI  - Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus.
      A randomized, controlled trial.
AB  - BACKGROUND: Compared with other insulin regimens, combination therapy with oral
      hypoglycemic agents and bedtime insulin produces similar improvement in glycemic
      control but induces less weight gain. OBJECTIVE: To determine whether bedtime
      insulin regimens differ with respect to their effects on weight gain in patients
      with type 2 diabetes. DESIGN: Randomized, controlled trial. SETTING: Four
      outpatient clinics at central hospitals. PATIENTS: 96 patients (mean age, 58 +/-
      1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly
      controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/
      0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).
      INTERVENTION: Random assignment to 1 year of treatment with bedtime intermediate
      acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo,
      glyburide and metformin, or a second injection of intermediate-acting insulin in
      the morning. Patients were taught to adjust the bedtime insulin dose on the basis
      of fasting glucose measurements. MEASUREMENTS: Body weight, biochemical and
      symptomatic hypoglycemias, and indices of glycemic control. RESULTS: At 1 year,
      body weight remained unchanged in patients receiving bedtime insulin plus
      metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups)
      but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients
      receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus
      both oral drugs, and those receiving bedtime and morning insulin, respectively.
      The greatest decrease in the glycosylated hemoglobin value was observed in the
      bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2%
      [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0
      months and P < 0.05 compared with other groups). This group also had
      significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05)
      than the other groups. CONCLUSIONS: Combination therapy with bedtime insulin plus
      metformin prevents weight gain. This regimen also seems superior to other bedtime
      insulin regimens with respect to improvement in glycemic control and frequency of
      hypoglycemia.

PMID- 10068413
TI  - Relation between influenza vaccination and outpatient visits, hospitalization,
      and mortality in elderly persons with chronic lung disease.
AB  - BACKGROUND: Influenza vaccine is underused in groups targeted for vaccination.
      OBJECTIVE: To define the effects of influenza and the benefits of influenza
      vaccination in elderly persons with chronic lung disease. DESIGN: Retrospective,
      multiseason cohort study. SETTING: Large managed care organization. PATIENTS: All
      elderly members of a managed care organization who had a previous diagnosis of
      chronic lung disease. MEASUREMENTS: Outcomes in vaccinated and unvaccinated
      persons for the 1993-1994, 1994-1995, and 1995-1996 influenza seasons were
      compared after adjustment for baseline demographic and health characteristics.
      All data were obtained from administrative databases. RESULTS: Vaccination rates
      were greater than 70% for each season. Among unvaccinated persons,
      hospitalization rates for pneumonia and influenza were twice as high in the
      influenza seasons as they were in the interim (noninfluenza) periods. Influenza
      vaccination was associated with fewer hospitalizations for pneumonia and
      influenza (adjusted risk ratio, 0.48 [95% CI, 0.28 to 0.82]) and with lower risk
      for death (adjusted odds ratio, 0.30 [CI, 0.21 to 0.43]) during the influenza
      seasons. It was also associated with fewer outpatient visits for pneumonia and
      influenza and for all respiratory conditions. CONCLUSIONS: For elderly persons
      with chronic lung disease, influenza is associated with significant adverse
      health effects and influenza vaccination is associated with substantial health
      benefits, including fewer outpatient visits, fewer hospitalizations, and fewer
      deaths. Health care providers should take advantage of all opportunities to
      immunize these high-risk patients.

PMID- 10068414
TI  - Delays in the suspicion and treatment of tuberculosis among hospitalized
      patients.
AB  - BACKGROUND: Despite increased awareness of tuberculosis, delays in management are
      common. OBJECTIVE: To investigate management delays among hospitalized patients
      with tuberculosis. DESIGN: Retrospective cohort study. SETTING: The Barnes-Jewish
      Christian Health System, a network of eight community and tertiary-care
      facilities serving the St. Louis, Missouri, metropolitan area. PATIENTS: All 203
      patients with tuberculosis hospitalized in the Barnes-Jewish-Christian Health
      System from 1988 to 1996. MEASUREMENTS: Time from admission to first
      consideration of the diagnosis (suspicion interval), first consideration and
      treatment initiation (treatment interval), and admission and treatment initiation
      (overall management interval) were determined. Delays were defined as intervals
      longer than 24 hours. RESULTS: The overall management interval (median, 6 days
      [5th and 95th percentiles, 1 and 52 days]) exceeded 24 hours in 152 patients
      (74.9% [95% CI, 68.9% to 80.9%]). The suspicion interval (median, 1 day [5th and
      95th percentiles, 0 and 16 days]) exceeded 24 hours in 54 patients (26.6% [CI,
      20.5% to 32.7%]), and the treatment interval (median, 3 days [5th and 95th
      percentiles, 0 and 51 days]) was prolonged in 130 patients (64.0% [CI, 57.4% to
      70.6%]). Overall management delays of more than 10 and 25 days occurred in 33.5%
      (CI, 27.0% to 40.0%) and 18.7% (CI, 13.3% to 24.1%) of patients, respectively.
      The 55 patients with smears that were positive for acid-fast bacilli had a median
      treatment interval of 3 days (5th and 95th percentiles, 0 and 33 days); in 58.2%
      of patients (CI, 45.2% to 71.2%), this interval exceeded 24 hours. CONCLUSIONS:
      Delays in initiation of treatment were more common than delays in the initial
      suspicion of tuberculosis. Both types of delays were common even in patients with
      disease that was confirmed by a positive smear. These data illustrate a need for
      improved education of physicians about the benefits of early initiation of
      therapy for tuberculosis.

PMID- 10068415
TI  - Prostanoids for chronic critical leg ischemia. A randomized, controlled, open
      label trial with prostaglandin E1. The ICAI Study Group. Ischemia Cronica degli
      Arti Inferiori.
AB  - BACKGROUND: No effective pharmacologic intervention is available for critical leg
      ischemia, a severe clinical condition associated with high morbidity and
      mortality. OBJECTIVE: To assess the safety and efficacy of prostaglandin E1 in
      improving the prognosis and quality of life in patients with critical leg
      ischemia. DESIGN: Multicenter, centrally randomized, controlled, open-label
      trial. SETTING: 56 vascular surgery and angiology departments of the Italian
      National Health Service. PATIENTS: 1560 patients with chronic critical leg
      ischemia. INTERVENTIONS: In addition to routine treatments practiced in each
      center, patients were randomly assigned to receive either a daily intravenous
      infusion of 60 microg of prostaglandin E1 in the form of alprostadil-alpha
      cyclodextrine (n = 771) or no prostaglandin E1 (n = 789) during their hospital
      stay. The treatment period lasted for up to 28 days. MEASUREMENTS: A combined end
      point consisting of death and peripheral and cardiocerebrovascular illness (major
      amputation or persistence of critical leg ischemia, acute myocardial infarction,
      or stroke) evaluated at hospital discharge and during 6 months of follow-up.
      RESULTS: The incidence of the combined outcome measure was lower in the
      alprostadil group than in controls at hospital discharge (493 [63.9%] patients
      compared with 581 [73.6%] patients; relative risk, 0.87 [95% CI, 0.81 to 0.93]; P
      < 0.001) but differed only modestly at 6 months (348 of 661 [52.6%] patients
      compared with 387 of 673 [57.5%] patients; relative risk, 0.92 [CI, 0.83 to
      1.01]; P = 0.074). Most of the observed benefit was due to recovery from critical
      leg ischemia. CONCLUSIONS: Short-term treatment with alprostadil-alpha
      cyclodextrine provides patients with critical leg ischemia clinical benefit that
      is apparent in the short term but decreases over time.

PMID- 10068416
TI  - Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three
      cases.
AB  - BACKGROUND: Takayasu arteritis is a rare form of chronic inflammatory disease of
      the large arterial vessels. Some patients do not respond to steroids or
      immunosuppressant drugs. OBJECTIVE: To evaluate the effect of mycophenolate
      mofetil in patients with severe Takayasu arteritis. DESIGN: Case series. SETTING:
      Clinical Research Center for Rare Diseases in Bergamo, Italy. PATIENTS: Three
      patients with Takayasu arteritis. INTERVENTION: Mycophenolate mofetil (2 g/d)
      given orally in two divided doses. MEASUREMENTS: Clinical evaluation and
      assessment of leukocyte counts were done weekly. Vascular lesions were assessed
      by using Doppler ultrasonography. RESULTS: All patients showed clinical benefit,
      and two resumed work after months of inactivity. Patients were also able to taper
      and discontinue steroid use. Mycophenolate mofetil was well tolerated, and no
      signs of toxicity were observed. CONCLUSIONS: Mycophenolate mofetil may be an
      alternative to steroids and cytotoxic agents in patients with Takayasu arteritis.
      Before results of controlled trials become available, mycophenolate mofetil
      should be considered only for patients who do not improve or stabilize with
      conventional therapy.

PMID- 10068417
TI  - Theophylline therapy for near-fatal Cheyne-Stokes respiration. A case report.
AB  - BACKGROUND: Cheyne-Stokes respiration is characterized by periodic breathing that
      alternates with hypopnea or apnea. OBJECTIVE: To describe the effect of
      theophylline on near-fatal Cheyne-Stokes respiration. DESIGN: Case report.
      SETTING: Tertiary referral center. PATIENT: A 48-year-old diabetic woman with a
      history of three cardiorespiratory arrests, a normal coronary arteriogram, normal
      left ventricular function, and severe Cheyne-Stokes respiration. MEASUREMENTS:
      Oxygen saturation, intra-arterial blood pressure, central venous pressure, chest
      wall movement, electrocardiography, electromyography, electroencephalography,
      electro-oculography, minute ventilation, arterial blood gases, and serum
      theophylline levels. RESULTS: After intravenous administration of 1.2 mg of
      theophylline at 0.6 mg/kg per hour (serum level, 5.6 microg/mL), both Cheyne
      Stokes respiration and oxygen desaturation were markedly attenuated. After
      infusion of 2.4 mg of theophylline (serum level, 11.6 microg/mL), Cheyne-Stokes
      respiration resolved completely. No change was seen with placebo. Cheyne-Stokes
      respiration did not recur during outpatient treatment with oral theophylline.
      CONCLUSION: Theophylline may be a rapid and effective therapy for life
      threatening Cheyne-Stokes respiration.

PMID- 10068418
TI  - Clinical effects of raloxifene hydrochloride in women.
AB  - PURPOSE: To review clinical data on raloxifene hydrochloride, a selective
      estrogen receptor modulator that was recently approved for the prevention of
      osteoporosis in postmenopausal women. DATA SOURCES: English-language articles
      published from 1980 to May 1998 were identified through MEDLINE searches.
      Bibliographies, book chapters, and meeting abstracts were reviewed for additional
      relevant publications. STUDY SELECTION: Publications that contained information
      on the background of development, structure, mechanism of action, tissue
      selective effects, and adverse effects of raloxifene hydrochloride were included.
      DATA EXTRACTION: Data in selected articles were reviewed, and relevant clinical
      information was extracted. DATA SYNTHESIS: Raloxifene hydrochloride was developed
      in an effort to find a treatment for breast cancer and osteoporosis. It binds to
      the estrogen receptor and shows tissue-selective effects; thus, it belongs to a
      class of drugs recently described as selective estrogen receptor modulators.
      Tissue selectivity of raloxifene may be achieved through several mechanisms: the
      ligand structure, interaction of the ligand with different estrogen receptor
      subtypes in various tissues, and intracellular events after ligand binding.
      Raloxifene has estrogen-agonistic effects on bone and lipids and estrogen
      antagonistic effects on the breast and uterus. An increase in bone mineral
      density at the spine, total hip, and total body has been reported with raloxifene
      but seems to be less than that seen with estrogen or alendronate therapy.
      Raloxifene has been shown to produce a reduction in total and low-density
      lipoprotein cholesterol concentrations similar to that produced by estrogen
      therapy, but high-density lipoprotein cholesterol and triglyceride concentrations
      do not increase during raloxifene therapy. In the uterus, raloxifene does not
      stimulate the endometrium. Long-term data on the effects of raloxifene in
      reduction of risk for fracture; prevention of cardiovascular events; cognitive
      function; and the incidence of breast, ovarian, and uterine cancer are not
      available. The most common adverse effect of raloxifene is hot flashes.
      CONCLUSIONS: Raloxifene has been shown to have beneficial effects in selected
      organs in postmenopausal women. Although estrogen remains the drug of choice for
      hormonal therapy in most postmenopausal women, raloxifene may be an alternative
      in certain groups of women at risk for osteoporosis.

PMID- 10068419
TI  - Treating type 2 diabetes with respect.

PMID- 10068420
TI  - Critical limb ischemia: nothing to give at the office?

PMID- 10068421
TI  - Seeking forgiveness.

PMID- 10068422
TI  - Trying to let go.

PMID- 10068423
TI  - Star treatment.

PMID- 10068424
TI  - Hospitalists: cost and quality of care.

PMID- 10068425
TI  - Hospitalists: cost and quality of care.

PMID- 10068426
TI  - Prevalence of hepatitis C virus infection in patients hospitalized for hepatitis
      A.

PMID- 10068427
TI  - Transfusion-transmitted virus and mixed cryoglobulinemia.

PMID- 10068428
TI  - Effects of hypertriglyceridemia on platelet counts in automated hematologic
      analysis.

PMID- 10068429
TI  - Access to health care, socioeconomic status, and health.

PMID- 10068430
TI  - Using practice guideline compendiums to provide better preventive care.

PMID- 10068440
TI  - Application of a thermodynamic model to the prediction of phase separations in
      freeze-concentrated formulations for protein lyophilization.
AB  - Many of the compounds considered for use in pharmaceutical formulations
      demonstrate incompatibilities with other components at high enough
      concentrations, including pairs of polymers, polymers and salts, or even proteins
      in combination with polymers, salts, or other proteins. Freeze concentration can
      force solutions into a region where incompatibilities between solutes will
      manifest as the formation of multiple phases. Such phase separation complicates
      questions of the stability of the formulation as well as labile components, such
      as proteins. Yet, phase separation events are difficult to identify by common
      formulation screening methods. In this report, we use the osmotic virial
      expansion model of Edmond and Ogston (1) to describe phase-separating behavior of
      ternary aqueous polymer solutions. Second osmotic virial coefficients of
      polyethylene glycol 3350 (PEG) and dextran T500 were measured by light
      scattering. Assuming an equilibrium between ice and water in the freeze
      concentrated solution, a degree of freeze concentration can be estimated, which,
      when combined with the phase separation spinodal, describes a "phase separation
      envelope" in which phase separation tendencies can be expected in the frozen
      solution. The phase separation envelope is bounded at low temperatures by the
      glass transition temperature of the freeze-concentrated solution. Scanning
      electron microscopic images and infrared spectroscopy of protein structure are
      provided as experimental evidence of the phase separation envelope in a freeze
      dried system of PEG, dextran, and hemoglobin.

PMID- 10068441
TI  - Function of a C-rich sequence in the polypyrimidine/polypurine tract of the
      promoter of the chicken malic enzyme gene depends on promoter context.
AB  - The promoters of many genes contain C-rich polypyrimidine/polypurine (PPY/PPU)
      sequences that are important for gene expression. The promoter of the chicken
      malic enzyme gene contains a long PPY/PPU tract that can act as an alternative
      promoter. This tract can be separated functionally into a C-rich and (CT)7
      sequences. The (CT)7 region together with some 3' nucleotides is essential for
      function of the alternative transcription start site and the C-rich sequence as a
      regulatory element. In constructs that contained the PPY/PPU tract or the 
      147/+31-bp promoter of the malic enzyme gene connected to a reporter gene,
      deletion of the C-rich region increased gene expression. In constructs containing
      5.8-kb 5'-flanking DNA of the gene, deletion of the same C-rich region decreased
      expression of the reporter gene. Positive function of the C-rich sequence
      required two upstream DNA regions, -237 to -147 bp and -3474 to -2715 bp. To
      understand the mechanism(s) by which the same sequence exerts different effects,
      we examined the transcription start sites in the construct where the C-rich
      region was deleted. We directly visualized transcription start sites by
      performing 5'-rapid amplification of cDNA ends and a subsequent primer extension
      on a single-stranded template. Deletion of the C-rich region from constructs
      containing 5.8 kb of 5'-flanking DNA almost completely abolished transcription
      initiation from the PPY/PPU promoter and reduced transcription from the major
      endogenous start site. DEAE fractionation of hepatic nuclear extract revealed
      more than 10 proteins that bound specifically to C-rich DNA. These results
      suggest that interactions between upstream DNA elements and the C-rich sequence
      and the selective use of DNA-binding activities may bestow different functions on
      the same nucleotide sequence.

PMID- 10068442
TI  - Fates and vascular action of S-nitrosoglutathione and related compounds in the
      circulation.
AB  - To know the metabolism of low-molecular-weight S-nitrosothiols (RS-NO) in the
      circulation, we analyzed the stability and depressor effects of S
      nitrosoglutathione (GS-NO) and the l- and d-forms of S-nitrosocysteine (Cys-NO).
      Although half-lives of these RS-NO in fresh plasma were longer than 50 min, their
      depressor effects disappeared within 5 min after intravenous administration of
      these compounds. Acivicin (AT-125), an inhibitor of gamma-glutamyltransferase
      (gamma-GTP), prolonged the depressor effect of GS-NO but not of Cys-NO. The
      depressor effect of GS-NO disappeared in AT-125-treated rats within 10 min after
      administration, which is still shorter than its half-life in vitro. Although S
      conjugates of l-cysteine, but not of d-cysteine, rapidly enter into cells via an
      active transport system and disappear from the circulation, both forms of Cys-NO
      exhibited similar activity to decrease blood pressure to that of NO. Thus, NO
      might be rapidly released from Cys-NO in the circulation and shortly exhibited
      its depressor action. These observations suggested that the circulating GS-NO is
      rapidly decomposed by gamma-GTP to form Cys-NO and that the release of NO from
      both GS-NO and Cys-NO is enhanced significantly in the circulation.

PMID- 10068443
TI  - Vitamin D receptor interacts with DnaK/heat shock protein 70: identification of
      DnaK interaction site on vitamin D receptor.
AB  - Vitamin D receptor (VDR) regulates the expression of vitamin D-dependent genes
      upon binding to its cognate ligand, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3).
      This process represents a complex interaction of ligand-bound VDR with nuclear
      proteins like retinoid X receptor, nuclear accessory factors, and regulatory
      elements of the target gene. Expression of full-length VDR in Escherichia coli
      revealed that VDR binds DnaK, a member of heat-shock protein (Hsp) family, with
      high affinity. By systematic N-terminal truncation of VDR, the interaction site
      of DnaK on VDR was localized within a 17-amino-acid segment (105-122)
      representing the "hinge region" between the DNA-binding and hormone-binding
      domains of VDR. The putative DnaK-binding site was further localized between
      residues 105 to 109 of VDR by using binding-energy-minimization studies. The
      interaction of DnaK with VDR did not influence the binding of 1,25(OH)2D3 or
      nuclear accessory factor(s) to VDR. Furthermore, bovine brain Hsp 70, similar to
      DnaK, interacted with VDR-ligand-binding domain (105-427). These results suggest
      that DnaK/Hsp 70 may interact with VDR prior to the activation of the latter by
      1,25(OH)2D3-binding.

PMID- 10068444
TI  - Modulation of the protein tyrosine kinase activity and autophosphorylation of the
      epidermal growth factor receptor by its juxtamembrane region.
AB  - Using peptides epidermal growth factor receptor (EGFR)-13 and EGFR-14, which
      correspond to residues 645-657 and 679-692, respectively, in the juxtamembrane,
      cytosolic region of the epidermal growth factor receptor (EGFR) we have
      investigated the role of specific regions of the receptor in regulating its
      autophosphorylation and protein tyrosine kinase activity. EGFR-13, but not EGFR
      14, increased autophosphorylation (by twofold) of the full-length and two
      truncated forms (Delta1022-1186 and a constitutively active receptor kinase
      domain) of the EGFR. EGFR-13 increased the stoichiometry of tyrosine
      phosphorylation of the full-length receptor from 4.2 to 10.1 mol Pi/mol EGFR and
      that of EGFRDelta1022-1186 from 1.0 to 2 mol Pi/mol receptor. Increased receptor
      autophosphorylation in the presence of EGFR-13 cannot solely be attributed to an
      increase in tyrosine kinase activity because EGFR-14 and polylysine increased
      tyrosine kinase activity of EGFRDelta1022-1186 and full-length EGFR,
      respectively, to the same extent as EGFR-13 without any effects on receptor
      autophosphorylation. Phosphorylation of EGFR-13 (P-EGFR-13) on the threonine
      residue corresponding to Thr654 in EGFR obliterated the ability of the peptide to
      increase autophosphorylation and markedly diminished its capacity to increase
      receptor tyrosine kinase activity. Additionally, EGFR-13, but not EGFR-14 or P
      EGFR-13, decreased the migration of the receptor on nondenaturing gels,
      indicating that EGFR-13 induces some conformational change. Phosphopeptide maps
      of the EGFR phosphorylated in the presence of EGFR-13 or pp60(c-src) demonstrated
      that the additional sites phosphorylated in the presence of EGFR-13 were the same
      as those phosphorylated by pp60(c-src) (i.e., Y803, Y845, Y891, Y920, and Y1101).
      Thus, we conclude that EGFR-13, but not EGFR-14 or P-EGFR-13, competes to disrupt
      interactions between amino acids 645-657 and some other region(s) on the EGFR to
      either alleviate a conformational constraint or alter dimer conformation. This
      change increases the protein tyrosine kinase activity of the EGFR and provides
      access to additional tyrosine autophosphorylation sites in the receptor.

PMID- 10068445
TI  - Purification and identification of two putative autolytic sites in human calpain
      3 (p94) expressed in heterologous systems.
AB  - Human muscle-specific calpain (CAPN3) was expressed in two heterologous systems:
      Sf9 insect cells and Escherichia coli cells. Polyclonal antibodies were prepared
      against peptides whose sequences were taken from the three unique regions of
      human CAPN3, namely NS, IS1, and IS2, which are not found in other members of the
      calpain family. Western blot analysis using these antibodies revealed that CAPN3
      was well expressed in both systems. However, considerable rapid degradation of
      the expressed CAPN3 was observed in both Sf9 and E. coli cells. These antibodies
      were therefore also used to detect CAPN3 and its degradation products in human
      and rat muscles, as well as to detect the protein throughout the purification of
      the recombinant His-tagged human CAPN3 by Ni2+ affinity chromatography and by
      immunopurification over immobilized antibody. An alternative purification
      procedure was used for purification of all putative CAPN3 immunoreactive
      fragments by combining SDS-PAGE and hydroxyapatite chromatography. Two fragments
      of CAPN3 of approximately 55 kDa were purified, and their N-terminal amino acid
      sequencing demonstrated that cleavage of CANP3 occurred between residues 30-31
      and 412-413, thus providing the first evidence for the localization of putative
      autolytic sites in this enzyme.

PMID- 10068446
TI  - Tumor promoter benzoyl peroxide induces sulfhydryl oxidation in protein kinase C:
      its reversibility is related to the cellular resistance to peroxide-induced
      cytotoxicity.
AB  - Since tumor promoter benzoyl peroxide (BPO) mimics phorbol esters in some
      aspects, its effects on protein kinase C (PKC) were previously studied. However,
      in those studies due to the presence of thiol agents in the PKC preparations, the
      sensitive reaction of BPO with redox-active cysteine residues in PKC was not
      observed. In this study, by excluding thiol agents present in the purified PKC
      preparation, low concentrations of BPO modified PKC, resulting in the loss of
      both kinase activity and phorbol ester binding (IC50 = 0. 2 to 0.5 microM). This
      modification, which was not dependent on transition metals, was totally blocked
      by a variety of thiol agents including GSH, which directly reacted with BPO.
      Substoichiometric amounts of BPO (0.4 mol/mol of PKC) oxidized two sulfhydryls in
      PKC and inactivated the enzyme which was readily reversed by dithiothreitol. The
      regulatory domain having zinc thiolate structures supporting the membrane
      inserting region provided the specificity for PKC reaction with BPO, which
      partitioned into the membrane. Unlike H2O2, BPO did not induce the generation of
      the Ca2+/lipid-independent activated form of PKC. Other redox-sensitive enzymes
      such as protein kinase A, phosphorylase kinase, and protein phosphatase 2A
      required nearly 25- to 100-fold higher concentrations of BPO for inactivation.
      BPO also inactivated PKC in a variety of cell types. In the JB6 (30 P-)
      nonpromotable cell line and other normal cell lines, where BPO was more
      cytotoxic, it readily inactivated PKC due to a slow reversibility of this
      inactivation by the cell. However, in the JB6 (41 P+) promotable cell line,
      C3H10T1/2 and B16 melanoma cells, where BPO was less cytotoxic, it did not
      readily inactivate PKC due to a rapid reversibility of this inactivation by an
      endogenous mechanism. Nevertheless, BPO inactivated PKC at an equal rate in the
      homogenates prepared from all these cell types. Inclusion of NADPH reversed this
      inactivation in the homogenates to a different extent, presumably due to a
      difference in distribution of a protein disulfide reductase, which reverses this
      oxidative modification. BPO-induced modification of PKC occurred independent of
      the cellular status of GSH. However, externally added GSH and cell-impermeable
      thiol agents prevented the BPO-induced modification of PKC. Since BPO readily
      partitions into membranes, its reaction with redox-cycling thiols of membrane
      proteins such as PKC may trigger epigenetic events to prevent cytotoxicity, but
      favor tumor promotion.

PMID- 10068447
TI  - The active site of phosphorylating glyceraldehyde-3-phosphate dehydrogenase is
      not designed to increase the nucleophilicity of a serine residue.
AB  - Changing a catalytic cysteine into a serine, and vice versa, generally leads to a
      dramatic decrease in enzymatic efficiency. Except a study done on thiol
      subtilisin, no extensive study was carried out for determining whether the
      decrease in activity is due to a low nucleophilicity of the introduced amino
      acid. In the present study, Cys149 of glyceraldehyde-3-phosphate dehydrogenase
      from Bacillus stearothermophilus was converted into a Ser residue. This leads to
      a drastic reduction of the kcat value. The rate-limiting step occurs before the
      hydride transfer step. Selective, but slow, inactivation is observed with
      specific, structurally different, inhibitors of serine protease. The esterolytic
      activity of serine mutant towards activated esters is also strongly decreased.
      The rate-limiting step of the esterase reaction also shifts from deacylation in
      the wild type to acylation in the mutant. Altogether, these results strongly
      suggest that the low catalytic efficiency of the Ser mutant is due to a poor
      nucleophilicity of the hydroxyl serine group within the active site of the
      enzyme. The fact that (1) the apo --> holo transition does not change esterolytic
      and inactivating efficiencies, and (2) Ser149 Asn176 double mutant exhibits the
      same chemical reactivity and esterolytic catalytic efficiency compared to the
      Ser149 single mutant indicates that the serine residue is not subject to His176
      general base catalysis. A linear relationship between the catalytic dehydrogenase
      rate, the kcat/KM for esterolysis, and the concentration of OH- is observed, thus
      supporting the alcoholate entity as the attacking reactive species. Collectively
      this study shows that the active site environment of GAPDH is not adapted to
      increase the nucleophilicity of a serine residue. This is discussed in relation
      to what is known about Ser and Cys protease active sites.

PMID- 10068448
TI  - NADP+-Dependent internalization of recombinant CD38 in CHO cells.
AB  - CD38 is a 46-kDa type II transmembrane glycoprotein that catalyses the synthesis
      of cyclic ADP-ribose (cADPR) from NAD+. cADPR is a second messenger known to
      regulate intracellular Ca2+-induced Ca2+-release (CICR). A recent study has
      revealed that CD38 in Namalwa B cells undergoes internalization upon exposure to
      external NAD+. In this study, recombinant rat CD38 was expressed in Chinese
      hamster ovary (CHO) cells and the possibility of the protein to undergo
      internalization upon exposure to a substrate analog NADP+ was examined. It was
      found that such treatment of CHO cells resulted in a decrease of ADP-ribosyl
      cyclase activity, as well as immunofluorescence of CD38 on the cell surface. The
      same treatment of CHO cells also resulted in intracellular clustering of CD38
      molecules as revealed by confocal microscopic analysis. The internalized CD38 was
      purified using a streptavidin/biotin-based method and was found to exhibit both
      ADP-ribosyl cyclase and cADPR hydrolase activities. On immunoblot, the
      internalized CD38 appeared as a monomer of 46 kDa under reducing condition of SDS
      PAGE. Our data demonstrate that NADP+ can efficiently induce internalization of
      CD38, a process that may be important in the production of cADPR intracellularly
      to regulate CICR.

PMID- 10068449
TI  - Molecular approaches to probe differential NADH activation of phosphoribulokinase
      isozymes from Rhodobacter sphaeroides.
AB  - The cbbPI and cbbPII genes from Rhodobacter sphaeroides, encoding highly similar
      phosphoribulokinase (PRK) isozymes, PRK I and PRK II, respectively, exhibited
      differential allosteric activation by NADH. The two cbbP genes were cloned into
      expression vectors and homogeneous recombinant protein prepared. PRK II was found
      to be inherently less stable than PRK I; however, the addition of substrate ATP
      resulted in the complete protection of both isozymes to a 15-min incubation at 50
      degrees C. The relative molecular masses for both octameric isozymes were
      determined to be approximately 230,000; however, the protective effect of ATP was
      in accordance with aggregation of monomers to a molecular mass of approximately
      750,000. While PRK I exhibited a nearly absolute dependence upon NADH for
      activity, PRK II retained substantial activity in the absence of NADH. PRK
      chimeras were thus constructed to facilitate elucidation of the basis for the
      differential effect of NADH, with advantage taken of the relative sequence
      identity of about 90% between the two isozymes. Chimeras were constructed either
      by in vivo homologous recombination, using the sacB gene from Bacillus subtilis
      as a conditionally lethal marker, or by using convenient restriction sites to
      combine different parts of the two cbbP genes. The PRK chimeras generated
      contained either the amino-terminal domain of PRK II and the carboxy-terminal
      domain of PRK I or the opposite configuration. Subsequent analyses of the
      chimeras pointed to particular regions and residue(s) as likely being important
      for NADH activation.

PMID- 10068450
TI  - Enhancement of cytotoxicity of hydrogen peroxide by hyperthermia in chinese
      hamster ovary cells: role of antioxidant defenses.
AB  - Regional hyperthermia has potential for human cancer treatment, particularly in
      combination with systemic chemotherapy or radiotherapy. The mechanisms involved
      in heat-induced cell killing are currently unknown. Hyperthermia may increase
      oxidative stress in cells, and thus, oxidative stress could have a role in the
      mechanism of cell death. We use hydrogen peroxide as a model oxidant to improve
      understanding of interactions between heat and oxidative stress. Heat increased
      cytotoxicity of hydrogen peroxide in Chinese hamster ovary cells. Altered levels
      of cellular antioxidants should create an imbalance between prooxidant and
      antioxidant systems, thus modifying cytotoxic responses to heat and to oxidants.
      We determine the involvement of the two cellular antioxidant defenses against
      peroxides, catalase and the glutathione redox cycle, in cellular sensitivity to
      heat, to hydrogen peroxide, and to heat combined with the oxidant. Defense
      systems were either inhibited or increased. For inhibition studies, intracellular
      glutathione was diminished to less than 15% of its initial level by treatment
      with L-buthionine sulfoximine (1 mM, 24 h). Inhibition of catalase was achieved
      with 3-amino-1,2,4-triazole (20 mM, 2 h), which caused a 80% decrease in
      endogenous enzyme activity. To increase antioxidants, cells were pretreated with
      the thiol-containing reducing agents, N-acetyl-L-cysteine, 2-oxo-4-thiazolidine
      carboxylate, and 2-mercaptoethane sulfonate. These compounds increased
      intracellular glutathione levels by 30%. Catalase activity was increased by
      addition of exogenous enzyme to cells. We show that levels of glutathione and
      catalase affect cellular cytotoxic responses to heat and hydrogen peroxide,
      either used separately or in combination. These findings are relevant to
      mechanisms of cell killing at elevated temperatures and suggest the involvement
      of oxidative stress.

PMID- 10068451
TI  - Identical subunit topographies of human and yeast 20S proteasomes.
AB  - The arrangement of subunits in human 20S proteasomes was recently determined by
      us by immunoelectron microscopy and chemical cross-linking. The positions of 4 of
      the 14 subunits differed from those found in the yeast proteasome by X-ray
      crystallography. Double labeling of human 20S proteasomes with antibodies to
      subunits C2 and C5 has now shown that these subunits are nearest neighbors. The
      result contradicts our published model for the human proteasome but is in
      accordance with the subunit arrangement in yeast proteasomes, suggesting that
      yeast and human proteasomes most probably have identical subunit arrangements.
      Immunoelectron microscopy also showed that the C-terminal extension at the human
      C2 subunit is flexible but takes up a well-defined position in the proteasome.

PMID- 10068452
TI  - Characterization of a novel NADH-specific, FAD-containing, soluble reductase with
      ferric citrate reductase activity from maize seedlings.
AB  - A novel NADH-dependent, soluble flavoreductase of 60 kDa, active toward ferric
      chelates and quinones, has been purified from maize seedlings. Two closely
      related isoforms were separated. The two isoforms are similar in several
      biochemical features, with the exception of the apparent molecular mass of their
      subunits (29 and 31 kDa, respectively). They are homodimers in the native state,
      they bind FAD as the prosthetic group and show strong preference for NADH over
      NADPH as the electron donor. Ferric chelates (chiefly ferric citrate, Km 3-5 x
      10(-5) M; kcat/Km 3.4-3.7 x 10(5) M-1 s-1), and some quinones (benzoquinone,
      coenzyme Q-0, and juglone) are used as electron acceptors. Enzymatic reduction of
      benzoquinone occurs with formation of radical semiquinones. Both soluble ferric
      chelate reductase isoforms are strongly inhibited by p-hydroxymercuribenzoic acid
      (I50 5 nM) and by cibachron blue, the latter giving nonlinear inhibition. It is
      suggested that soluble ferric chelate reductase might be involved in the
      symplastic reduction of iron chelates which is required for the assembly of iron
      containing macromolecules such as cytochromes and ferritin.

PMID- 10068453
TI  - Substrate specificity of a nitroalkane-oxidizing enzyme.
AB  - The flavoprotein nitroalkane oxidase from Fusarium oxysporum catalyzes the
      oxidation of nitroalkanes to aldehydes with production of hydrogen peroxide and
      nitrite. The substrate specificity of the FAD-containing enzyme has been
      determined as a probe of the active site structure. Nitroalkane oxidase is active
      on primary and secondary nitroalkanes, with a marked preference for unbranched
      primary nitroalkanes. The V/K values for primary nitroalkanes increase with
      increasing length of the alkyl chain, reaching a maximum with 1-nitrobutane,
      suggesting a hydrophobic binding site sufficient to accommodate a four carbon
      chain. Each methylene group of the substrate contributes approximately 2.6 kcal
      mol-1 in binding energy. The V/K values for substrates containing a hydroxyl
      group are two orders of magnitude smaller than those of the corresponding
      nitroalkanes, also consistent with a hydrophobic binding site. 3-Nitro-1
      propionate is a competitive inhibitor with a Kis value of 3.1 +/- 0.2 mM.

PMID- 10068454
TI  - The effects of mono-ADP-ribosylation on desmin assembly-disassembly.
AB  - Previous studies have shown that desmin, the muscle-specific intermediate
      filament protein, is a substrate for the endogenous muscle arginine-specific mono
      ADP-ribosyltransferase and that ADP-ribosylation inhibits assembly of desmin into
      intermediate filaments (Huang et al., Exp. Cell Res. 226, 147-153, 1996). In this
      paper, the effects of mono-ADP-ribosylation on assembly and disassembly of desmin
      intermediate filaments were further characterized. First, it was found that ADP
      ribosylated desmin does not coassemble with unmodified desmin and has no effect
      on assembly of unmodified desmin. Second, incubation of assembled desmin
      filaments with mono-ADP-ribosyltransferase and NAD+ results in disassembly of the
      filaments. Finally, the structural components of the attached ADP-ribose moiety
      responsible for altering the assembly of desmin into filaments were investigated
      by a stepwise cleavage of ADP-ribose with snake venom phosphodiesterase and
      alkaline phophatase, followed by analysis of assembly. The reactions catalyzed by
      these two enzymes were established using a desmin peptide as a substrate. Our
      results show that ribosylated desmin, but not phosphoribosylated desmin, was able
      to self-assemble into intermediate filaments, suggesting that the presence of a
      phosphate group is needed to alter desmin's assembly ability.

PMID- 10068455
TI  - Cloning of an L-3-hydroxyacyl-CoA dehydrogenase that interacts with the GLUT4 C
      terminus.
AB  - Evidence indicates that the carboxy-terminal cytoplasmic domain of glucose
      transporter 4 (GLUT4) is important for the regulation of GLUT4 in muscle and
      adipocytes. We cloned from a human skeletal muscle cDNA library a 34-kDa protein
      which interacts with GLUT4 C-terminal cytoplasmic domain in a two-hybrid system
      and also with GLUT4 C-terminus synthetic peptide in an in vitro binding assay.
      This protein, called YP10, showed a high degree (>90%) of sequence homology with
      l-3-hydroxyacyl-CoA dehydrogenase (HAD) and had a dehydrogenase activity similar
      to pig heart HAD, which was inhibited by GLUT4 C-terminus synthetic peptide. An
      antiserum raised against pig heart HAD also reacted with YP10. Western blot
      analysis using this antiserum revealed abundant immunoreactivity only in the
      mitochondria- and plasma membrane-enriched fractions of rat adipocytes. Northern
      blots revealed that YP10 mRNA is most abundant in skeletal and heart muscle.
      These findings suggest that YP10, a HAD isoform, interacts with GLUT4 at the
      plasma membrane and may play a role in cross-talk between glucose transport and
      fatty acid metabolism.

PMID- 10068456
TI  - The effect of alpha-tocopherol on the nitration of gamma-tocopherol by
      peroxynitrite.
AB  - It has been proposed (S. Christen et al. Proc. Natl. Acad. Sci. USA 94, 3217
      3222, 1997) that although alpha-tocopherol (alpha-TH) is an efficient
      antioxidant, the presence of gamma-tocopherol (gamma-TH) may be required to
      scavenge peroxynitrite-derived reactive nitrogen species. To investigate the
      reactions between alpha-TH, gamma-TH, and peroxynitrite, endogenous levels of
      both alpha-TH and gamma-TH were monitored when low-density lipoprotein was
      oxidized in the presence of the peroxynitrite generator 5-amino-3-(4-morpholinyl)
      1, 2,3-oxadiazolium (SIN-1). SIN-1 oxidized alpha-TH while gamma-TH levels
      remained constant. The sparing of gamma-TH was also demonstrated when 1,2
      dilauroyl-sn-glycero-3-phosphocholine liposomes containing alpha-TH and gamma-TH
      were incubated with either SIN-1 or peroxynitrite. Our data show that alpha-TH
      inhibits peroxynitrite-mediated gamma-TH nitration, i.e., 5-NO2-gamma-tocopherol
      formation. The rate constants for the reactions between both alpha-TH and gamma
      TH with peroxynitrite suggest that the sparing of gamma-TH by alpha-TH does not
      occur by competitive scavenging, but may be due to the formation of a transient
      gamma-TH intermediate. Nitration of gamma-TH becomes significant only after alpha
      TH levels have been depleted. We conclude alpha-TH alone is sufficient to remove
      any peroxynitrite-derived reactive nitrogen species, as the presence of alpha-TH
      attenuates nitration of both gamma-TH and tyrosine. The present results also
      indicate that a bolus addition of peroxynitrite or SIN-1 to liposomes containing
      gamma-TH forms 5-NO2-gamma-tocopherol in similar yields. This is in contrast to
      their reaction profile with tyrosine in aqueous solution. Under these conditions,
      SIN-1 does not form nitrotyrosine at detectable yields.

PMID- 10068457
TI  - Expression of cytokines and activation of transcription factors in
      lipopolysaccharide-administered rats and their inhibition by phenyl N-tert
      butylnitrone (PBN).
AB  - The spin-trapping compound phenyl N-tert-butylnitrone (PBN) affords protection
      from the lethality of septic shock in rodents. Previous studies have shown that
      PBN elicits its protection by inhibiting inducible nitric oxide synthase (iNOS)
      induction. In the present study, using the lipopolysaccharide (LPS) rat septic
      shock model, we determined the expression of various cytokine genes (tumor
      necrosis factor (TNF)-alpha, TNF-beta, interferon (IFN)-gamma, interleukin (IL)
      1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-10) and the activation of
      transcription factors nuclear factor kappaB (NF-kappaB) and activator protein-1
      (AP-1) in the liver tissue, 30 min and 3 h after LPS administration. The effects
      of PBN preadministration on the production levels were also investigated. The
      results show that LPS (4 mg/kg, ip) induced the production of the cytokine genes
      and increased the nuclear protein level of NF-kappaB within 30 min after LPS
      administration. Preadministration of PBN (150 mg/kg, ip) significantly down
      regulated the production of cytokine genes (TNF-alpha by 94%, IL-1 by 63%, and IL
      1 by 70%) and reduced the nuclear protein level of NF-kappaB by 75% and AP-1 by
      72% at 3 h after LPS injection. These results demonstrate that PBN, in addition
      to its iNOS induction inhibition, also has multiple anti-inflammatory effects in
      septic shock, via modulation of the production of the key inflammatory mediators.

PMID- 10068458
TI  - The contribution of acidic residues to the conformational stability of common
      type acylphosphatase.
AB  - Common-type acylphosphatase is a small cytosolic enzyme whose catalytic
      properties and three-dimensional structure are known in detail. All the acidic
      residues of the enzyme have been replaced by noncharged residues in order to
      assess their contributions to the conformational stability of acylphosphatase.
      The enzymatic activity parameters and the conformational free energy of each
      mutant were determined by enzymatic activity assays and chemically induced
      unfolding, respectively. Some mutants exhibit very similar conformational
      stability, DeltaG(H2O), and specific activity values as compared to the wild-type
      enzyme. By contrast, six mutants show a significant reduction of conformational
      stability and two mutants are more stable than the wild-type protein. Although
      none of the mutated acidic residues is directly involved in the catalytic
      mechanism of the enzyme, our results indicate that mutations of residues located
      on the surface of the protein are responsible for a structural distortion which
      propagate up to the active site. We found a good correlation between the free
      energy of unfolding and the enzymatic activity of acylphosphatase. This suggests
      that enzymatic activity measurements can provide valuable indications on the
      conformational stability of acylphosphatase mutants, provided the mutated residue
      lies far apart from the active site. Moreover, our results indicate that the
      distortion of hydrogen bonds rather than the loss of electrostatic interactions,
      contributes to the decrease of the conformational stability of the protein.

PMID- 10068459
TI  - Characterization of free alpha- and beta-chains of recombinant macrophage
      stimulating protein.
AB  - Human serum macrophage-stimulating protein (MSP) induces motile activity of
      murine resident peritoneal macrophages and is a growth and motility factor for
      epithelial cells. It belongs to the plasminogen-related family of kringle
      proteins, and is secreted as a single-chain, 78-kDa, biologically inactive pro
      MSP. Proteolytic cleavage of pro-MSP at a single site yields active MSP, a
      disulfide-linked alphabeta-chain heterodimer. However cleavage of recombinant pro
      MSP yielded not only the disulfide-linked heterodimer, but also free alpha- and
      beta-chains, indicating that some of the recombinant molecules lacked an
      alphabeta-chain disulfide. We purified the free chains for characterization. The
      beta-chain of MSP has three extra cysteines, Cys527, Cys562, and Cys672, which
      are not found in the plasminogen beta-chain. Disulfide bond analysis showed a
      Cys527-Cys562, but also a Cys588-Cys672. Coopting Cys588 by Cys672 prevented the
      expected formation of a disulfide between alpha-chain Cys468 and beta-chain
      Cys588. Concomitant studies determined structures of oligosaccharides at the
      three Asn-linked glycosylation sites of MSP. The oligosaccharides at the three
      Asn loci are heterogeneous; 11 different sugars were identified, all being
      sialylated fucosyl biantennary structures. We also located the pro-MSP signal
      peptide cleavage site at Gly18-Gln19 and the scissile bond for formation of
      mature MSP at Arg483-Val484.

PMID- 10068460
TI  - Cationomycin and monensin partition between serum proteins and erythrocyte
      membrane: consequences for Na+ and K+ transport and antimalarial activities.
AB  - The ionophore properties of cationomycin and monensin were studied on human
      erythrocytes by measuring Na+ influx by 23Na NMR and concomitant K+ efflux by
      potentiometry in the presence of increasing amounts of serum. Both ion currents
      (Na+ or K+) decreased linearly with the reciprocal of serum amount. The serum
      effects on ion currents were stronger with cationomycin than with monensin.
      Assuming this decreased transport activity was due to drug binding to serum
      proteins, a partition coefficient between the protein and the membrane phase was
      determined for each ionophore by using a novel model. This partition coefficient
      is about 30 times higher for cationomycin than for monensin; the same result was
      obtained with purified human serum albumin, indicating that albumin may be the
      major ionophore binding protein of serum. In parallel, we also measured IC50 for
      50% in vitro growth inhibition of Plasmodium falciparum, the agent of malaria. In
      the presence of increasing serum concentrations, the antimalarial activity was
      decreased for both ionophores. Serum effect was less severe for monensin than for
      cationomycin, in agreement with the weaker interaction of monensin with proteins
      as shown from the partition coefficient values. A correlation was established
      between the ion transport currents (sodium and potassium) and the IC50 measured
      on P. falciparum in the presence of the various concentrations of serum. The
      relative value of the ion transport currents (expressed as percentage of control
      in absence of serum) can be indicative of the ionophore unbound fraction in the
      medium.

PMID- 10068461
TI  - Can foreign proteins imported into yeast mitochondria interfere with PIM1p
      protease and/or chaperone function?
AB  - When studying the fate of mammalian apocytochrome P450scc (apo-P450scc) imported
      in small amounts into isolated yeast mitochondria, we found that it undergoes
      degradation, this process being retarded if recipient mitochondria are preloaded
      in vivo (to about 0.2% of total organelle protein) with a fusion protein composed
      of mammalian adrenodoxin reductase and adrenodoxin (AdR-Ad); in parallel we
      observed aggregation of apo-P450scc. These effects suggest some overload of Pim1p
      protease and/or mtHsp70 system by AdR-Ad, as both of them are involved in the
      degradation of apo-P450scc (see Savel'ev et al. J. Biol. Chem. 273, 20596-20602,
      1998). However, under the same conditions AdR-Ad was not able to impede the
      import of proteins into mitochondria and the development of the mitochondrial
      respiratory machinery in yeast, the processes requiring the mtHsp70 system and
      Pim1p, respectively. These data imply that chaperones and Pim1p protease prefer
      their natural targets in mitochondria to imported foreign proteins.

PMID- 10068462
TI  - Neural precursor cells differentiating in the absence of Rb exhibit delayed
      terminal mitosis and deregulated E2F 1 and 3 activity.
AB  - The severe neurological deficit in embryos carrying null mutations for the
      retinoblastoma (Rb) gene suggests that Rb plays a crucial role in neurogenesis.
      While developing neurons undergo apoptosis in vivo neural precursor cells
      cultured from Rb-deficient embryos appear to differentiate and survive. To
      determine whether Rb is an essential regulator of the intrinsic pathway
      modulating terminal mitosis we examined the terminal differentiation of primary
      cortical progenitor cells and bFGF-dependent neural stem cells derived from Rb
      deficient mice. Although Rb -/- neural precursor cells are able to differentiate
      in vitro we show that these cells exhibit a significant delay in terminal mitosis
      relative to wild-type cells. Furthermore, Rb -/- cells surviving in vitro exhibit
      an upregulation of p107 that is found in complexes with E2F3. This suggests that
      p107 may partially compensate for the loss of Rb in neural precursor cells.
      Functional ablation of Rb family proteins by adenovirus-mediated delivery of an
      E1A N-terminal mutant results in apoptosis in Rb-deficient cells, consistent with
      the interpretation that other Rb family proteins may facilitate differentiation
      and survival. While p107 is upregulated and interacts with the putative Rb target
      E2F3 in neural precursor cells, our results indicate that it clearly cannot
      restore normal E2F regulation. Rb-deficient cells exhibit a significant
      enhancement of E2F 1 and 3 activity throughout differentiation concomitant with
      the aberrant expression of E2F-inducible genes. In these studies we show that Rb
      is essential for the regulation of E2F 1 and 3 activity as well as the onset of
      terminal mitosis in neural precursor cells.

PMID- 10068463
TI  - A subpopulation of apoptosis-prone cardiac neural crest cells targets to the
      venous pole: multiple functions in heart development?
AB  - A well-described population of cardiac neural crest (NC) cells migrates toward
      the arterial pole of the embryonic heart and differentiates into various cell
      types, including smooth muscle cells of the pharyngeal arch arteries (but not the
      coronary arteries), cardiac ganglionic cells, and mesenchymal cells of the
      aortopulmonary septum. Using a replication-incompetent retrovirus containing the
      reporter gene LacZ, administered to the migratory neural crest of chicken
      embryos, we demonstrated another population of cardiac neural crest cells that
      employs the venous pole as entrance to the heart. On the basis of our present
      data we cannot exclude the possibility that precursors of these cells might not
      only originate from the dorsal part of the posterior rhombencephalon, but also
      from the ventral part. These NC cells migrate to locations surrounding the
      prospective conduction system as well as to the atrioventricular (AV) cushions.
      Concerning the prospective conduction system, the tagged neural crest cells can
      be found in regions where the atrioventricular node area, the retroaortic root
      bundle, the bundle of His, the left and right bundle branches, and the right
      atrioventricular ring bundle are positioned. The last area connects the
      posteriorly located AV node area with the retroaortic root bundle, which receives
      its neural crest cells through the arterial pole in concert with the cells giving
      rise to the aortopulmonary septum. The NC cells most probably do not form the
      conduction system proper, as they enter an apoptotic pathway as determined by
      concomitant TUNEL detection. It is possible that the NC cells in the heart become
      anoikic and, as a consequence, fail to differentiate further and merely die.
      However, because of the perfect timing of the arrival of crest cells, their
      apoptosis, and a change in electrophysiological behavior of the heart, we
      postulate that neural crest cells play a role in the last phase of
      differentiation of the cardiac conduction system. Alternatively, the separation
      of the central conduction system from the surrounding working myocardium is
      mediated by apoptotic neural crest cells. As for the presence of NC cells in both
      the outflow tract and the AV cushions, followed by apoptosis, a function is
      assigned in the muscularization of both areas, resulting in proper septation of
      the outflow tract and of the AV region. Failure of normal neural crest
      development may not only play a role in cardiac outflow tract anomalies but also
      in inflow tract abnormalities, such as atrioventricular septal defects.

PMID- 10068464
TI  - Development of cephalic neural crest cells in embryos of Lampetra japonica, with
      special reference to the evolution of the jaw.
AB  - Neural crest cells contribute extensively to vertebrate head morphogenesis and
      their origin is an important question to address in understanding the evolution
      of the craniate head. The distribution pattern of cephalic crest cells was
      examined in embryos of one of the living agnathan vertebrates, Lampetra japonica.
      The initial appearance of putative crest cells was observed on the dorsal aspect
      of the neural rod at stage 20.5 and ventral expansion of these cells was first
      seen at the level of rostral somites. As in gnathostomes, cephalic crest cells
      migrate beneath the surface ectoderm and form three major cell populations, each
      being separated at the levels of rhombomeres (r) 3 and r5. The neural crest seems
      initially to be produced at all neuraxial levels except for the rostral-most
      area, and cephalic crest cells are secondarily excluded from levels r3 and r5.
      Such a pattern of crest cell distribution prefigures the morphology of the
      cranial nerve anlage. The second or middle crest cell population passes medial to
      the otocyst, implying that the otocyst does not serve as a barrier to separate
      the crest cell populations. The three cephalic crest cell populations fill the
      pharyngeal arch ventrally, covering the pharyngeal mesoderm laterally with the
      rostral-most population covering the premandibular region and mandibular arch.
      The third cell population is equivalent to the circumpharyngeal crest cells in
      the chick, and its influx into the pharyngeal region precedes the formation of
      postotic pharyngeal arches. Focal injection of DiI revealed the existence of an
      anteroposterior organization in the neural crest at the neurular stage, destined
      for each pharyngeal region. The crest cells derived from the posterior midbrain
      that express the LjOtxA gene, the Otx2 cognate, were shown to migrate into the
      mandibular arch, a pattern which is identical to gnathostome embryos. It was
      concluded that the head region of the lamprey embryo shares a common set of
      morphological characters with gnathostome embryos and that the morphological
      deviation of the mandibular arch between the gnathostomes and the lamprey is not
      based on the early embryonic patterning.

PMID- 10068465
TI  - Retinal neurogenesis: the formation of the initial central patch of postmitotic
      cells.
AB  - We have investigated the relationship between the birthdate and the onset of
      differentiation of neurons in the embryonic zebrafish neural retina. Birthdates
      were established by a single injection of bromodeoxyuridine into embryos of
      closely spaced ages. Differentiation was revealed in the same embryos with a
      neuron-specific antibody, zn12. The first bromodeoxyuridine-negative
      (postmitotic) cells occupied the ganglion cell layer of ventronasal retina, where
      they formed a small cluster of 10 cells or less that included the first zn12
      positive cells (neurons). New cells were recruited to both populations
      (bromodeoxyuridine-negative and zn12-positive) along the same front, similar to
      the unfolding of a fan, to produce a circular central patch of hundreds of cells
      in the ganglion cell layer about 9 h later. Thus the formation of this central
      patch, previously considered as the start of retinal neurogenesis, was actually a
      secondary event, with a developmental history of its own. The first neurons
      outside the ganglion cell layer also appeared in ventronasal retina, indicating
      that the ventronasal region was the site of initiation of all retinal
      neurogenesis. Within a column (a small cluster of neuroepithelial cells),
      postmitotic cells appeared first in the ganglion cell layer, then the inner
      nuclear layer, and then the outer nuclear layer, so cell birthday and cell fate
      were correlated within a column. The terminal mitoses occurred in three bursts
      separated by two 10-h intervals during which proliferation continued without
      terminal mitoses.

PMID- 10068466
TI  - Histone ubiquitination and chromatin remodeling in mouse spermatogenesis.
AB  - Male infertility in HR6B knockout mice is associated with impairment of
      spermatogenesis. The HR6B gene is a mammalian, autosomal homolog of the
      Saccharomyces cerevisiae gene Rad6 encoding a ubiquitin-conjugating enzyme. In
      addition, X-chromosomal HR6A has been identified, in human and mouse. RAD6 in
      yeast is required for a variety of cellular functions, including sporulation, DNA
      repair, and mutagenesis. Since RAD6 and its mammalian homologs can ubiquitinate
      histones in vitro, we have investigated the pattern of histone ubiquitination in
      mouse testis. By immunoblot and immunohistochemical analysis of wild-type mouse
      testis, a high amount of ubiquitinated H2A (uH2A) was detected in pachytene
      spermatocytes. This signal became undetectable in round spermatids, but then
      increased again during a relatively short developmental period, in elongating
      spermatids. No other ubiquitinated histones were observed. In the HR6B knockout
      mice, we failed to detect an overt defect in the overall pattern of histone
      ubiquitination. For somatic cell types, it has been shown that histone
      ubiquitination is associated with destabilization of nucleosomes, in relation to
      active gene transcription. Unexpectedly, the most intense uH2A signal in
      pachytene spermatocytes was detected in the sex body, an inactive nuclear
      structure that contains the heterochromatic X and Y chromosomes. The postmeiotic
      uH2A immunoexpression in elongating spermatids indicates that nucleosome
      destabilization induced by histone ubiquitination may play a facilitating role
      during histone-to-protamine replacement.

PMID- 10068467
TI  - Treatment of mouse oocytes with PI-PLC releases 70-kDa (pI 5) and 35- to 45-kDa
      (pI 5.5) protein clusters from the egg surface and inhibits sperm-oolemma binding
      and fusion.
AB  - The effect of phosphatidyinositol-specific phospholipase C (PI-PLC) on mouse
      sperm-egg interaction was investigated in this study to determine if glycosyl
      phosphatidylinositol (GPI)-anchored proteins are involved in mammalian
      fertilization. When both sperm and zona-intact oocytes were pretreated with a
      highly purified preparation of PI-PLC and coincubated, there was no significant
      effect on sperm-zona pellucida binding; however, fertilization was reduced from
      59.6% (control group) to 2.8% (treatment group). A similar reduction in
      fertilization rates was found when zona-intact oocytes were treated with PI-PLC
      and washed prior to incubation with untreated sperm. The effect of PI-PLC on
      sperm binding and fusion with zona-free oocytes was then investigated. Treatment
      of sperm with PI-PLC had no significant effect on sperm-egg binding or fusion.
      However, treatment of eggs with PI-PLC significantly reduced sperm-egg binding
      and fusion from 6.2 bound and 2.1 fused sperm per egg in the control group to 2.1
      bound and 0.02 fused sperm per egg in the treatment group. This decrease in sperm
      egg binding and fusion depended on the dose of PI-PLC employed, with a maximal
      inhibitory effect on binding and fusion at 5 and 1 U/ml, respectively. PI-PLC
      treated oocytes could be artificially activated by calcium ionophore,
      demonstrating that the oocytes were functionally viable following treatment.
      Furthermore, treatment of oocytes with PI-PLC did not reduce the immunoreactivity
      of the non-GPI-anchored egg surface integrin, alpha6beta1. Taken together, these
      observations support the hypothesis that PI-PLC affects fertilization by
      specifically releasing GPI-anchored proteins from the oolemma. In order to
      identify the oolemmal GPI-anchored proteins involved in fertilization, egg
      surface proteins were labeled with sulfo-NHS biotin, treated with PI-PLC, and
      analyzed by two-dimensional gel electrophoresis followed by avidin blotting. A
      prominent high-molecular-weight protein cluster (approximately 70 kDa, pI 5) and
      a lower molecular weight (approximately 35-45 kDa, pI 5.5) protein cluster were
      released from the oolemmal surface as a result of PI-PLC treatment. It is likely
      that these GPI-anchored egg surface proteins are required for sperm-egg binding
      and fusion.

PMID- 10068468
TI  - Misexpression of the catenin p120(ctn)1A perturbs Xenopus gastrulation but does
      not elicit Wnt-directed axis specification.
AB  - Modulators of cadherin function are of great interest given that the cadherin
      complex actively contributes to the morphogenesis of virtually all tissues. The
      catenin p120(ctn) (formerly p120cas) was first identified as a src- and receptor
      protein tyrosine kinase substrate and later shown to interact directly with
      cadherins. In common with beta-catenin and plakoglobin (gamma-catenin), p120(ctn)
      contains a central Armadillo repeat region by which it binds cadherin cytoplasmic
      domains. However, little is known about the function of p120(ctn) within the
      cadherin complex. We examined the role of p120(ctn)1A in early vertebrate
      development via its exogenous expression in Xenopus. Ventral overexpression of
      p120(ctn)1A, in contrast to beta-catenin, did not induce the formation of
      duplicate axial structures resulting from the activation of the Wnt signaling
      pathway, nor did p120(ctn) affect mesoderm induction. Rather, dorsal
      misexpression of p120(ctn) specifically perturbed gastrulation. Lineage tracing
      of cells expressing exogenous p120(ctn) indicated that cell movements were
      disrupted, while in vitro studies suggested that this may have been a consequence
      of reduced adhesion between blastomeres. Thus, while cadherin-binding proteins
      beta-catenin, plakoglobin, and p120(ctn) are members of the Armadillo protein
      family, it is clear that these proteins have distinct biological functions in
      early vertebrate development. This work indicates that p120(ctn) has a role in
      cadherin function and that heightened expression of p120(ctn) interferes with
      appropriate cell-cell interactions necessary for morphogenesis.

PMID- 10068469
TI  - Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and disrupt axis
      formation in Xenopus.
AB  - Smads are central mediators of signal transduction for the TGFbeta superfamily.
      However, the precise functions of Smad-mediated signaling pathways in early
      development are unclear. Here we demonstrate a requirement for Smad2 signaling in
      dorsoanterior axis formation during Xenopus development. Using two point
      mutations of Smad2 previously identified in colorectal carcinomas, we show that
      Smad2 ushers Smad4 to the nucleus to form a transcriptional activation complex
      with the nuclear DNA-binding protein FAST-1 and that the mutant proteins interact
      normally with FAST-1 but fail to recruit Smad4 into the nucleus. This mechanism
      of inhibition specifically restricts the dominant-negative activity of these
      mutants to the activin/Vg1 signaling pathway without inhibiting BMPs.
      Furthermore, expression of these mutants in Xenopus animal caps inhibits but does
      not abolish activin and Vg1 induction of mesoderm and in the embryo results in a
      truncated dorsoanterior axis. These studies define a mechanism through which
      mutations in Smad2 may block TGFbeta-dependent signaling and suggest a critical
      role for inductive signaling mediated by the Smad2 pathway in Xenopus organizer
      function.

PMID- 10068470
TI  - Gap junction signalling mediated through connexin-43 is required for chick limb
      development.
AB  - During chick limb development the gap junction protein Connexin-43 (Cx43) is
      expressed in discrete spatially restricted domains in the apical ectodermal ridge
      (AER) and mesenchyme of the zone of polarising activity. Antisense
      oligonucleotides (ODNs) were used to investigate the role of Connexin-43 (Cx43)
      in the development of the chick limb bud. We have used unmodified ODNs in
      Pluronic F-127 gel, which is liquid at low temperature but sets at room
      temperature and so remains situated at the point of application. As a mild
      surfactant, the gel increases antisense ODN penetration and supplies ODNs to the
      embryo continually for 12-18 h. We have shown a strong decrease in Cx43 protein
      expression after application of specific antisense oligonucleotides but the
      abundance of a closely related protein, Connexin-32 (Cx32), was not affected.
      Application of antisense Cx43 ODNs at stages 8-15 HH before limb outgrowth
      resulted in dramatic limb phenotypes. About 40% of treated embryos exhibited
      defects such as truncation of the limb bud, fragmentation into two or more
      domains, or complete splitting of the limb bud into two or three branches.
      Molecular analysis of antisense treated embryos failed to detect Shh or Bmp-2 in
      anterior structures and suggested that extra lobes seen in nicked and split limbs
      were not a result of establishment of new signalling centres as found after the
      application of FGF to the flank. However, examination of markers for the AER
      showed a number of abnormalities. In severely truncated specimens we were unable
      to detect the expression of either Fgf-4 or Fgf-8. In both nicked and split limbs
      the expression of these genes was discontinuous. Down-regulation of Cx43 after
      the antisense application could be comparable to AER removal and results in
      distal truncation of the limb bud. Taken together these data suggest the
      existence of a feedback loop between the FGFs and signalling mediated by Cx43.

PMID- 10068471
TI  - A novel follicle-cell-dependent dominant female sterile allele, StarKojak, alters
      receptor tyrosine kinase signaling in Drosophila.
AB  - We describe a new dominant allele, StarKojak, that alters receptor tyrosine
      kinase signaling in the follicle cells and in the eyes in Drosophila. We isolated
      StarKojak in a screen for follicle-cell-dependent dominant female sterile
      mutations. We show that StarKojak and revertants of StarKojak do not complement
      Star loss-of-function mutations. We propose that StarKojak is a novel type of
      allele of Star that has both dominant gain-of-function phenotypes early in
      development and dominant loss-of-function phenotypes later in development. Star
      encodes a putative transmembrane protein that has previously been shown to be a
      critical component of the epidermal growth factor receptor tyrosine kinase
      signaling pathway. Early in oogenesis, Star mRNA expression is higher in
      StarKojak egg chambers than in wild-type egg chambers, consistent with its gain
      of-function phenotype. Later in oogenesis, Star mRNA expression is lower in
      StarKojak follicle cells than in wild-type follicle cells, consistent with its
      loss-of-function phenotype. By genetically analyzing StarKojak and its
      revertants, we present evidence that Star is involved in anterior-posterior axis
      formation both in the female germline cells and in the somatic follicle cells. We
      also demonstrate that at least part of the dominant female sterile phenotype of
      StarKojak is restricted to the posterior-pole follicle cells. We propose that
      Star functions by processing pro-Gurken to mature Gurken, which is thereby
      released in the region between the oocyte and the follicle cells and binds to the
      epidermal growth factor receptor in the follicle cells.

PMID- 10068472
TI  - Regulation of meiosis during mammalian spermatogenesis: the A-type cyclins and
      their associated cyclin-dependent kinases are differentially expressed in the
      germ-cell lineage.
AB  - To begin to examine the function of the A-type cyclins during meiosis in the
      male, we have examined the developmental and cellular distribution of the cyclin
      A1 and cyclin A2 proteins, as well as their candidate cyclin-dependent kinase
      partners, Cdk1 and Cdk2, in the spermatogenic lineage. Immunohistochemical
      localization revealed that cyclin A1 is present only in male germ cells just
      prior to or during the first, but not the second, meiotic division. By contrast,
      cyclin A2 was expressed in spermatogonia and was most abundant in preleptotene
      spermatocytes, cells which will enter the meiotic pathway. Immunohistochemical
      detection of Cdk1 was most apparent in early pachytene spermatocytes, while
      staining intensity diminished in diplotene and meiotically dividing
      spermatocytes, the cells in which cyclin A1 expression was strongest. Cdk2 was
      highly expressed in all spermatocytes. Notably, in cells undergoing the meiotic
      reduction divisions, Cdk2 appeared to localize specifically to the chromatin.
      This was not the case for spermatogonia undergoing mitotic divisions. In the
      testis, cyclin A1 has been shown to bind both Cdk1 and Cdk2 but we show here that
      cyclin A2 binds only Cdk2. These results indicate that the A-type cyclins and
      their associated kinases have different functions in the initiation and passage
      of male germ cells through meiosis.

PMID- 10068473
TI  - Expression pattern of Brachyury and Not in the sea urchin: comparative
      implications for the origins of mesoderm in the basal deuterostomes.
AB  - This work concerns the expression of two transcription factors during the
      development of the sea urchin Strongylocentrotus purpuratus: SpNot, the
      orthologue of the vertebrate Not gene, and SpBra, the orthologue of the
      vertebrate Brachyury gene. SpNot transcripts are detected by in situ
      hybridization in the vegetal plate at the mesenchyme-blastula stage. Later the
      gene is expressed in the secondary mesenchyme, but expression is no longer
      detectable after gastrulation. SpNot is upregulated during larval development, in
      the invaginating vestibule of the adult rudiment. Transcripts are also found in
      several larva-specific tissues, including the epaulets, blastocoelar cells, and
      pigment cells. SpBra also displays a discontinuous pattern of expression. Much
      like SpNot, this gene is expressed during embryogenesis in the embryonic vegetal
      plate and secondary mesenchyme founder cells, and expression is then
      extinguished. The gene is upregulated over a week later in the feeding larva, in
      the vestibule of the adult rudiment. In contrast to SpNot, SpBra is also
      expressed in the mesoderm of both left and right hydrocoels, and it is not
      expressed in any larva-specific tissues. We compare the spatial expression
      profile determined in this study with that of the orthologous Brachyury gene in
      an indirectly developing enteropneust hemichordate, a representative of the
      sister group to the echinoderms within the deuterostomes. These observations
      illuminate the genetic basis underlying the process of maximal indirect
      development in basal deuterostomes. Finally, Brachyury appears to be an excellent
      marker for the progeny of the set-aside cells of the sea urchin embryo.

PMID- 10068474
TI  - Involvement of Chk1 kinase in prophase I arrest of Xenopus oocytes.
AB  - Chk1 kinase, a DNA damage/replication G2 checkpoint kinase, has recently been
      shown to phosphorylate and inhibit Cdc25C, a Cdc2 Tyr-15 phosphatase, thereby
      directly linking the G2 checkpoint to negative regulation of Cdc2. Immature
      Xenopus oocytes are arrested naturally at the first meiotic prophase (prophase I)
      or the late G2 phase, with sustained Cdc2 Tyr-15 phosphorylation. Here we have
      cloned a Xenopus homolog of Chk1, determined its developmental expression, and
      examined its possible role in prophase I arrest of oocytes. Xenopus Chk1 protein
      is expressed at approximately constant levels throughout oocyte maturation and
      early embryogenesis. Overexpression of wild-type Chk1 in oocytes prevents the
      release from prophase I arrest by progesterone. Conversely, specific inhibition
      of endogenous Chk1 either by overexpression of a dominant-negative Chk1 mutant or
      by injection of a neutralizing anti-Chk1 antibody facilitates prophase I release
      by progesterone. Moreover, when ectopically expressed in oocytes, a Chk1
      nonphosphorylatable Cdc25C mutant alone can induce prophase I release much more
      efficiently than wild-type Cdc25C; if endogenous Chk1 function is inhibited,
      however, even wild-type Cdc25C can induce the release very efficiently. These
      results suggest strongly that Chk1 is involved in physiological prophase I arrest
      of Xenopus oocytes via the direct phosphorylation and inhibition of Cdc25C. We
      discuss the possibility that Chk1 might function either as a G2 checkpoint kinase
      or as an ordinary cell cycle regulator in prophase-I-arrested oocytes.

PMID- 10068475
TI  - The synthesis of a small heat shock/alpha-crystallin protein in Artemia and its
      relationship to stress tolerance during development.
AB  - Fertilized oocytes of the brine shrimp Artemia franciscana undergo either
      ovoviviparous or oviparous development, yielding free-swimming larvae (nauplii)
      or encysted gastrulae (cysts), respectively. Encystment is followed by diapause,
      wherein metabolism is greatly reduced; the resulting cysts are very resistant to
      extreme stress, including desiccation and long-term anoxia. The synthesis of p26,
      a small heat shock/alpha-crystallin protein produced only in oviparously
      developing Artemia, is shown in this paper to be transcriptionally regulated. A
      p26 mRNA of about 0.7 kb was detected on Northern blots in the second day after
      oocyte fertilization. It peaked as embryos encysted and declined rapidly when
      activated cysts resumed development. The appearance of p26 protein, as indicated
      by immunoprobing of Western blots, followed mRNA by 1 day; it also increased as
      encystment occurred but remained constant during postgastrula development of
      cysts. However, p26 underwent a marked reduction during emergence of nauplii and
      could not be detected in cell-free extracts of second-instar larvae. p26 entered
      nuclei of encysting embryos soon after synthesis and was localized therein as
      late as instar II, when it was restricted to a small set of salt gland nuclei.
      First-instar larvae derived from cysts were more thermotolerant than larvae that
      had developed ovoviviparously, but synthesis of p26 was not induced by heat under
      the experimental conditions employed. Additionally, transformed bacteria
      synthesizing p26 were more thermotolerant than bacteria that lacked the protein.
      The results support the proposal that p26, a developmentally regulated protein
      synthesized during embryo encystment, has chaperone activity in vivo and protects
      the proteins of encysted Artemia from stress-induced denaturation.

PMID- 10068476
TI  - Discrete regional distributions suggest diverse functional roles of calcium
      channel alpha1 subunits in sperm.
AB  - The Ca channels of male germ-line cells are partially characterized, but the
      molecular properties and subcellular localization of the Ca channels of mature
      sperm are unknown. Here, we probe rodent sperm with anti-peptide antibodies
      directed to cytosolic domains of cloned rat brain alpha1A, alpha1C, and alpha1E
      Ca channel subunits. Each recognizes a 200- to 245-kDa band on immunoblots of
      whole rat sperm extracts. A smaller ( approximately 110-kDa) alpha1C band also is
      detected. Confocal fluorescence images of mouse sperm show characteristic
      patterns of punctate alpha1A-, alpha1C-, and alpha1E-immunoreactivity. For
      alpha1A, the puncta are larger, less numerous, and more variable in distribution
      than for alpha1C and alpha1E. They are absent from the acrosomal crescent, but
      are present elsewhere over the sperm head, often at the apical tip and equatorial
      segment. They also are found at irregular intervals along both the midpiece and
      the principal piece of the flagellum. For alpha1C and alpha1E, puncta are dense
      along dorsal and ventral aspects of the acrosomal cap. For alpha1E but not
      alpha1C, the remainder of the acrosomal region also is labeled. Neither is found
      in the postacrosomal region or on the midpiece. Puncta of alpha1C and alpha1E
      occur at regular intervals each in two parallel rows, at the dorsal and ventral
      aspects of the proximal segment of the flagellar principal piece. The puncta in
      these arrays become less abundant and intense in the distal flagellum. These
      results demonstrate that multiple Ca channel proteins are present in mature sperm
      and are regionally localized in ways that may give them different regulatory
      roles.

PMID- 10068477
TI  - Activin and TGFbeta limit murine primordial germ cell proliferation.
AB  - Mammalian primordial germ cells (PGCs) proliferate as they migrate from their
      initial location in the extraembryonic mesoderm to the genital ridge, the gonadal
      anlage. Once in the genital ridge, PGCs cease dividing and differentiate
      according to their gender. To identify ligands that might limit PGC
      proliferation, we analyzed growth factor receptors encoded in RNA obtained from
      purified germ cells shortly after their arrival in the genital ridge. Receptors
      for two members of the TGFbeta superfamily were found, TGFbeta1 and activin. As
      the signal-transducing domains of both receptor systems are highly conserved, the
      effects of both TGFbeta1 and activin on PGCs would be expected to be similar. We
      found that both ligands limited the accumulation of germ cells in primary PGC
      cultures. BrdU incorporation assays demonstrated that either ligand inhibits PGC
      proliferation. These results suggest that these signal transduction pathways are
      important elements of the mechanism that determines germ cell endowment.

PMID- 10068478
TI  - Volume 202, number 2 (1998), in article no. DB989010, "FREAC-1 contains a cell
      type-specific transcriptional activation domain and is expressed in epithelial
      mesenchymal Interfaces," by margit mahlapuu, markku pelto-huikko, marjo aitola,
      sven Enerback, and peter carlsson, pages 183-195 

PMID- 10068479
TI  - Volume 204, number 1 (1998), in article no. DB989075, "Bottle cells are required
      for the initiation of primary invagination in the sea urchin Embryo," by
      elizabeth laxson kimberly and jeff hardin, pages 235-250 

PMID- 10068480
TI  - The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of
      melanosomal proteins in the eye.
AB  - The pink-eyed dilution (p) locus is known to control the quantity of melanin
      pigment made within melanocytes and retinal pigment epithelium (RPE) in the eye.
      We have examined the effects of several mutant allele combinations at the murine
      p locus on the number and morphology of melanosomes in choroidal melanocytes and
      RPE cells as well as on the levels of four proteins known to be present within
      melanosomes: tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2)
      and lysosome-associated membrane protein-1 (LAMP-1). By electron microscopy, we
      observed a modest diminution in the size and number of choroidal melanosomes in
      pbs/pJ mice but a more dramatic decrease in the RPE in comparison with wild-type
      P/P mice. By contrast, a drastic reduction in melanosome size and number was
      present in the choroid and RPE of pun/pun and p6H/pcp mice, and in the RPE of
      p6H/pcp mice, melanosomes were essentially undetectable. In wild-type mice,
      levels of tyrosinase, TRP-1 and TRP-2 were high at birth and showed a second peak
      of expression at 10-14 days of age, declining to undetectable levels by 42 days.
      All three mutant allele combinations reduced the levels of these melanosomal
      proteins with the relative severity of effects being p6H/pcp>pun/pun>pbs/pJ. In
      the null p6H/pcp mice, levels of these proteins were extremely low at birth, no
      postnatal peak was observed, and levels declined to undetectable by 14 days.
      Levels of LAMP-1 in wild-type mice rose initially and then declined whereas in
      the mutant mice, levels decreased gradually from birth. Higher levels of LAMP-1
      were observed in each of the mutants than in the wild-type mice at 21 days of
      age. Our results demonstrate that mutations at the p locus affect the size,
      number, shape and contents of melanosomes, implicating the p gene product in the
      normal biogenesis of this organelle.

PMID- 10068481
TI  - Modulation of scleral DNA synthesis in development of and recovery from induced
      axial myopia in the tree shrew.
AB  - Visually modulated scleral extracellular matrix remodelling is associated with
      the development of, and recovery from, induced axial myopia in the tree shrew, a
      commonly used mammalian model of refractive error development. The involvement of
      scleral cell proliferation in this process was investigated using [3H] thymidine.
      Tree shrews were monocularly deprived of pattern vision, using translucent
      occluders, or the retinal image was optically defocused, using negative lenses,
      over a period of 5 days. A further group was monocularly deprived for 5 days,
      then allowed 3 days of binocular recovery. A control group of binocularly open
      animals was employed to establish normal parameters. On the final day of the
      experimental period, [3H] thymidine was administered by intraperitoneal
      injection, then optical and biometric measures were taken and tissue samples
      collected for assay. Incorporation of [3H] thymidine into cellular DNA was
      measured in proteinase K digests, following precipitation with trichloroacetic
      acid. After 5 days, significant amounts of myopia were present in the treated
      eyes of both form-deprived [-7. 0+/-0.7 Dioptres (D), group mean+/-s.e.m.;
      P<0.01] and lens-defocused animals (-6.2+/-0.9 D;P<0.01). After 3 days of
      recovery, 50% of the refractive error had been compensated for, predominantly
      through shortening of the vitreous chamber in the treated eye. Reduced levels of
      [3H] thymidine incorporation were observed in sclera from both groups of myopic
      animals (form-deprived, -34.3+/-9.9%;P<0.05 and lens-defocus, -32.8+/
      4.5%;P<0.005). Increased levels of [3H] thymidine incorporation were found in the
      sclera of recovering animals (+144.0+/-43.2%;P<0.05). The results show that
      changes in regulation of cell proliferation, during the development of myopia,
      are visually mediated and inversely related to the direction of change in ocular
      size. This implies that alterations in the scleral fibroblast population are
      involved in the modulation of scleral matrix turnover during myopia development.

PMID- 10068482
TI  - Swelling activated chloride channels in cultured bovine corneal endothelial
      cells.
AB  - Swelling induced enhancement of anion permeability was investigated using the
      halide-sensitive fluorescent dye SPQ in cultured bovine corneal endothelial cells
      (BCEC). Rates of anion influx were quantified in terms of the rate of change of
      SPQ fluorescence during exposure to short duration pulses of Cl-, I-or NO3-while
      the cells were being perfused with I-, NO3-or Cl-Ringer, respectively. Since SPQ
      fluorescence is quenched to different extents by these anions, their influx or
      efflux causes significant changes in fluorescence. The ratio of the maximum rate
      of change of fluorescence during the pulse period under hyposmotic conditions to
      that under isosmotic conditions, referred to as the enhancement ratio (ER), was
      calculated as a measure of the increase in anion permeability. When cells were
      perfused with NO3-Ringer, exposure to I-pulses yielded an ER=9.0+/-2.6 for 110+/
      5 mosmhyposmotic shock. This was higher than with Cl-/I-(6.4+/-0.7) or NO3-/Cl
      (3.2+/-0.8) anion-pairs for the same level of shocks. In all cases, the
      enhancement occurred within approximately 100 seconds after swelling but
      decreased with continued progress of regulatory volume decrease (RVD). ER
      returned to approximately 1 within 4 minutes after returning to isosmotic
      conditions. The membrane potential (Em) depolarized immediately after hyposmotic
      shock. When cells were depolarized prior to the shocks by high [K+], changes in
      Emwere relatively small. ER, for the NO3-/I-anion-pair, was significantly reduced
      by DIDS (100% at 500 microm), NPPB ( approximately 80% at 100 microm) and
      tamoxifen (approximately 85% at 12 microm). Tamoxifen and NPPB also inhibited
      swelling induced depolarization. Increasing cationic conductance with Gramicidin
      D at approximately 2 minutes following hyposmotic shock induced NPPB-inhibitable
      secondary swelling or accelerated RVD under normal or low Na+conditions,
      respectively. These results demonstrate that BCEC express swelling activated Cl
      channels, which facilitate RVD by enhancing anionic permeability and also by
      providing a favorable electrical gradient for K+efflux.

PMID- 10068483
TI  - Ubiquitin-dependent pathway is up-regulated in differentiating lens cells.
AB  - The mammalian eye lens is composed of two distinct types of cells, epithelial
      cells and fiber cells. The fiber cells are generated throughout life via
      continuous differentiation of epithelial cells. Differentiation of lens cells
      involves dramatic changes in cellular components including altered activity of
      the ubiquitin dependent pathway. The concentration of high mass ubiquitin
      conjugates in the mitotically active-, differentiating-equatorial epithelial
      cells was 5-10 fold higher than that observed in mitotically quiescent, non
      differentiated, central epithelial cells, even though there was a significant
      dilution of non-crystallin proteins due to an increase in level of crystallins in
      the differentiating cells. Similar observations were made when differentiation
      was modeled by exposure of lens epithelial explants to bFGF in culture.
      Activities of ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes
      (E2s) in the differentiating equatorial epithelial cells were also up to 100%
      higher than those noted in non-differentiated central epithelial cells and E1
      appears to be rate controlling for ubiquitinylation. Consistent with the higher
      concentrations of high mass ubiquitin conjugates, there was a trend of enhanced
      ability to execute ATP-dependent protein degradation in the differentiating
      equatorial epithelial cells as compared with degradation in the non
      differentiated central epithelial cells. These data indicate that the ubiquitin
      dependent pathway is up-regulated during differentiation of lens cells. In the
      differentiated fibers, the concentration of high mass ubiquitin conjugates and
      relative activities of E1 and E2s were 50% lower than in the non-differentiated
      central epithelial cells. In comparison, the concentration of the 110 kDa E1 was
      unchanged in differentiated fibers. However, if the factor of dilution by the
      significant increase in the level of crystallins was taken into account, the
      level or activities of the components of ubiquitin pathway in the differentiated
      cells was higher than the level noted in non-differentiated cells. These data
      indicate that, as compared with other non-crystallin proteins, there is
      differential stabilization and/or synthesis of the 110 kDa E1 and some other
      components of the ubiquitin dependent pathway in differentiated fibers.

PMID- 10068484
TI  - Regulation by transforming growth factor-beta 1 of G1 cyclin-dependent kinases in
      human retinal epithelial cells.
AB  - Transforming growth factor beta (TGFbeta) is a potent inhibitor of epithelial
      cell proliferation, delaying or arresting cell cycle progression in mid-late G1.
      In long-term life span cells this growth inhibitory action has been attributed to
      regulatory events on both the levels and activities of G1 cyclin-dependent
      kinases (CDKs). CDK inhibitors have been shown to play important role in the
      TGFbeta-induced inhibition of G1 CDKs. In this work, we have investigated the
      effect of TGFbeta1 on both cell proliferation and G1 CDK activities in primary
      cultures of human retinal pigment epithelial (RPE) cells. We show that TGFbeta1
      exerts a partial inhibitory effect on RPE cell proliferation by causing a
      significant increase of the RPE cell number in G1. TGFbeta1 induces an up
      regulation of the CDK inhibitor p15(INK4B)with its subsequent association to
      CDK4, and a decline in CDK4 protein level. In parallel, we have observed a
      decline of p27(KIP1)associated to CDK4 and a significant increase of the
      inhibitor associated to CDK2. Finally, we show that TGFbeta1 reduces both CDK4
      and CDK2 enzymatic activities. The fact that TGFbeta exerts only partial
      inhibitions on G1 CDKs and cell cycle progression in RPE cells suggests a
      propensity of these cells to escape from the anti-proliferative action of the
      cytokine, a phenomenon which could be reinforced during the development of
      proliferative vitreoretinopathy.

PMID- 10068485
TI  - Rek, an Axl/Tyro3-related receptor-class tyrosine kinase, is expressed in Muller
      glia and differentiating neural subpopulations in the avian retina.
AB  - Rek is a receptor-class tyrosine kinase of the Axl/Tyro3 family that has
      transforming capability and is expressed in the avian nervous system. To gain
      insight into its normal cellular function, the spatial and temporal expression of
      Rek was analyzed in the developing chick retina by immunoperoxidase staining and
      Western blotting using Rek-specific antibodies. Rek was developmentally regulated
      in the retina with maximal expression of the 140 kD full-length kinase at
      embryonic stage 34 (E8), when retinal glia and neurons begin to differentiate.
      Rek immunoreactivity was most prominent in the processes of developing and mature
      retinal Muller glia, and appeared transiently in the bodies of differentiating
      ganglion and amacrine neurons. In the developing optic tract Rek was found in
      oligodendroglial-type cells but not in ganglion cell axons. Rek antibodies also
      stained brain ependymal cells and some cerebellar neuronal cell types (Purkinje,
      basket and stellate cells). This expression pattern suggests that the Rek
      tyrosine kinase participates in an aspect of Muller glial function, and may also
      contribute to the development of restricted populations of glia and neurons in
      the brain and retina.

PMID- 10068486
TI  - Iris vasculopathy in galactose-fed rats.
AB  - Increased iris vessel permeability observed in diabetics has also been reported
      to occur in diabetic animals and galactose-fed rats. The potential role of aldose
      reductase in the induction of iris vessel changes has been investigated in rats
      fed a 50% galactose diet with/without the aldose reductase inhibitors AL 1576,
      sorbinil or ponalrestat for 7 to 18 months. Compared to normal control rats, long
      term galactose-fed rats display a breakdown of the blood-aqueous barrier due to
      iris vessel changes that include focal straightening, dilation, constriction,
      increased permeability, ischemia and new vessel proliferation. The onset and
      progression of these iridal vessel changes were prevented by the aldose reductase
      inhibitors AL 1576 and sorbinil, and reduced by Ponalrestat. Computerized
      analyses of lumen areas of iris vessels indicated an 18-fold decrease in the
      vascular area near the pupillary boarder in untreated galactose-fed rats compared
      with age-matched controls and galactose-fed rats treated with aldose reductase
      inhibitors. These observations linking iris vessel changes with galactose
      feeding, coupled with the fact that aldose reductase inhibitors also prevent
      these changes, strongly suggest a link between the sorbitol pathway and the
      appearance and progression of iris vessel changes.

PMID- 10068487
TI  - Critical period for retinoic acid-induced developmental abnormalities of the
      vitreous in mouse fetuses.
AB  - To elucidate the underlying developmental mechanisms of persistent hyperplastic
      primary vitreous (PHPV) in humans, we investigated a mouse model for PHPV induced
      by retinoic acid. We treated C57BL/6NJcl mice at various stages of pregnancy
      (gestation days 7, 8, 9, 10, 11, or 12) with the teratogen retinoic acid, which
      affects the migration of neural crest cells. Untreated pregnant mice served as a
      control group. The eyes of the fetuses were examined histologically on day 18 on
      gestation. Developmental abnormalities of the vitreous were defined as the
      presence of excessive mesenchymal tissue in the vitreous cavity. The incidence of
      developmental abnormalities of the vitreous in all groups, except for those
      treated on day 12 of pregnancy, significantly exceeded that in the control group
      (P<0.01). The histological characteristics of the observed vitreous abnormalities
      in mice resembled those found in PHPV clinically. Retinoic acid-induced
      abnormalities in mice can serve as an experimental model for PHPV by
      environmental factors. Results suggest that the critical period for these
      retinoic acid-induced abnormalities was during days 7 to 11 of gestation, which
      corresponds to a critical period of 2.5 to 7 weeks of gestation for PHPV in
      humans.

PMID- 10068488
TI  - Neutral and acidic glycosphingolipids in glucocorticoid-induced cataract in chick
      lens.
AB  - Administration of glucocorticoids induces transient cataract in 15-day-old chick
      embryos within 48 hr, and the opaque lens again becomes clear within the
      subsequent 48 hr. Oxidative stress is likely to be involved in the process of
      cataract formation, resulting in the appearance of numerous vacuoles around the
      perinuclear region. Chick lens contained low amounts of glycosphingolipids, which
      mainly consists of GM3, GD3, sialyl-LewisX gangliosides and glucosylceramide.
      Most lens gangliosides were immunohistochemically detected in lens epithelia,
      annular pads and developing fibers, but not in perinuclear and nuclear regions.
      Since cell surface gangliosides, for example GM3 and sialyl-LewisX gangliosides,
      are involved in cell adhesion, weak cell-to-cell interactions in the perinuclear
      and nuclear regions may allow vacuole formation in steroid-induced
      cataractogenesis.

PMID- 10068489
TI  - Melanin granules of retinal pigment epithelium are connected with the lysosomal
      degradation pathway.
AB  - Melanosomes are closely related to lysosomes and lipofuscin granules. This paper
      indicates the potential involvement of lysosomal degradation processes in retinal
      pigment epithelial (RPE) cells. RPE cells cultured on Bruch's membrane and
      choroid were fed with indigestible latex beads. The RPE cells from this
      preparation were treated with chloroquine to investigate whether membrane
      swelling, typical for lysosomes under this condition, can be induced in
      melanosomes. To investigate the fate of indigestible material associated with rod
      outer segments (ROS), gold-labeled ROS were injected transsclerally into the
      subretinal space of Long Evans rats using a 32 gauge Hamilton syringe. The
      degradation of labeled ROS was observed after 5 and 12 days by electron
      microscopy. The following results were observed. Latex particles fuse with the
      melanin granules of the RPE. Following chloroquine treatment, the membranes of
      melanin granules fused, and formed large clusters and vacuoles. Gold granules
      were detected inside both early stage melanosomes and mature melanin granules of
      the RPE cells 5 and 12 days following subretinal injection of the labeled ROS.
      Higher numbers of gold granules were predominantly found in immature melanosomes
      containing still melanofilaments and in small fused mature melanin granules. In
      conclusion the effect of chloroquine clearly demonstrates that the melanosomes
      possess active proton pumps which is typical for lysosomes. In RPE cells stressed
      by overload with rod outer segments or by ingestion of undegradable material
      (latex beads, gold particles), fusion of these phagosomes with melanosomes of
      different maturity is more a general rule than an exception. Therefore,
      melanosomes are connected to lysosomal pathways in RPE cells.

PMID- 10068490
TI  - Physical properties of stimulated and unstimulated tears.
AB  - It has long been assumed that unstimulated tears are more thoroughly equilibrated
      with epithelial secretions than stimulated tears, since they are in contact with
      tarsal, bulbar and corneal surfaces for longer. It was also believed from results
      with model solutions that soluble mucin is responsible for the observed surface
      tension and viscosity of tears. If longer contact means more mucin is dissolved
      in the aqueous tears, then the surface activity (surface tension lowered by
      mucin) and viscosity (raised by mucin) of tears should therefore be enhanced in
      unstimulated over stimulated tears. Pools of stimulated and minimally-stimulated
      tears were collected from a group of healthy adult volunteers by glass capillary.
      Viscosities were measured in the Contraves Low Shear 30 rheometer over the range
      of shear rates 0-130 sec-1. Surface tension was measured in the collection
      capillaries by a micro-technique, before and after refrigerated storage. Both
      surface tension and viscosity were determined for a variety of tear proteins and
      mucins. No significant difference was found between the viscosity/shear rate
      plots of stimulated and unstimulated tear samples. The viscosities of solutions
      of individual tear proteins were low, except for the combination of lysozyme and
      secretory IgA. Surface tensions were also similar in both cases, and unchanged by
      storage at room temperature or refrigeration, indicating no significant loss of
      surface-active material by adsorption on the capillary walls. Results with model
      mucin solutions gave a variety of results indicating either little surface
      activity or losses due to wall adsorption. Tear proteins, individually or in
      combination, did not lower surface tension to the level of tears. Tear viscosity
      seems not to depend on the level of dissolved mucins. This suggests either that a
      constant level of these is picked up even by short-term contact with ocular
      surfaces, or that viscosity arises from currently unknown materials which vary
      little with tear flow rate. This type of shear-dependent viscosity is most easily
      simulated in model solutions with polyionic linear macromolecules, including
      mucins. The contribution of individual proteins to overall viscosity is small,
      but combinations including lysozyme show tear-like characteristics, and may
      indicate that proteins whose concentration is relatively independent of tear flow
      rate combine with other tear components (possibly including mucins or lipids) to
      produce their full effect on tear viscosity. The surface tension results suggest
      that mucins are not of primary importance. Theories of tear film structure and
      performance need revision.

PMID- 10068491
TI  - Detection of melatonin, its precursors and related enzyme activities in rabbit
      lens.
AB  - Melatonin (N -acetyl-5-methoxytryptamine) was detected in extracts of albino
      rabbit lens using radioimmunoassay. Furthermore, melatonin precursors, tryptophan
      and serotonin (5-hydroxytryptamine), were found in the lens extracts by high
      performance liquid chromatography coupled with fluorometric detection. Also,
      activities of two melatonin-synthesizing enzymes, serotonin N -acetyltransferase
      (NAT) and hydroxyindole- O -methyltransferase (HIOMT), were found in the lens.
      The apparent Michaelis constants (K m) for substrates of NAT in the lens were
      similar to those reported for the pineal gland, although the apparent K m values
      for substrates of HIOMT in the lens were 10-fold higher than those in the pineal
      gland. When the rabbits were entrained to a 14-hr light: 10-hr dark cycle,
      melatonin levels and NAT activity in the lens showed significant day/night
      changes with high levels during the dark period, but HIOMT activity did not show
      these changes. These findings strongly suggest that the rabbit lens may
      synthesize melatonin from serotonin by the sequential action of NAT and HIOMT,
      and that the melatonin synthesis may fluctuate in a diurnal and/or circadian
      manner.

PMID- 10068492
TI  - Announcements 

PMID- 10068493
TI  - Volume Contents and Index.

PMID- 10068494
TI  - Effects of vasoactive intestinal peptide on plasma prolactin in passerines.
AB  - Vasoactive intestinal peptide (VIP) is a potent releaser of prolactin (PRL) in
      domestic fowl, turkey, and ring doves. However, few comparative studies have
      investigated this in wild species. We tested the effects of intravenously
      administered chicken VIP on plasma PRL concentrations in four passerine species:
      the white-crowned sparrow (Zonotrichia leucophrys gambelii), the dark-eyed junco
      (Junco hyemalis), the Florida scrub-jay (Aphelocoma coerulescens), and the
      western scrub-jay (A. californica). In the white-crowned sparrow, junco, and
      Florida scrub-jay, which were tested during the breeding season, VIP induced a
      rapid increase in plasma PRL. Serial plasma samples taken after VIP injection in
      the white-crowned sparrow show a 10-fold increase in PRL within 2 min of
      treatment, followed by a gradual decline. Effects of VIP, as compared to saline,
      remained significant for at least 20 min after treatment. Western scrub-jays did
      not respond to intravenous VIP with a significant rise in PRL secretion, possibly
      because they were tested after termination of the breeding season. This study
      indicates that VIP control of PRL release may be widespread among avian species,
      and that seasonal changes in plasma PRL may be mediated in part at the level of
      the pituitary. In addition, analysis of the control data revealed no increase in
      plasma PRL as a result of injection or restraint, suggesting that unlike in
      mammals, PRL is not released during acute stress in passerines.

PMID- 10068495
TI  - Effects of insulin-like growth factor-I and cortisol on Na+, K+-ATPase expression
      in osmoregulatory tissues of brown trout (Salmo trutta).
AB  - The effect of recombinant bovine IGF-I (rbIGF-I) on hypo-osmoregulatory ability
      and the effect of rbIGF-I and cortisol (F) alone and in combination on Na+,K+
      ATPase expression in fresh water (FW) acclimated brown trout (Salmo trutta) were
      examined in two experiments. In Experiment 1, fish were given three injections of
      saline or 0.01 or 0.1 microgram rbIGF-I/g, respectively, and subjected to a 24-h
      25 ppt seawater (SW) challenge test 24 h after the last injection. Fish treated
      with 0.01 and 0.1 microgram rbIGF-I/g had better hypo-osmoregulatory ability than
      control fish as judged by their higher level of muscle water content and lower
      plasma osmolality after 24 h exposure to 25 ppt SW. Compared with control fish,
      gill Na+,K+-ATPase activity was unchanged 24 h after the first injection at
      either dose but significantly stimulated after three injections of either dose of
      rbIGF-I. In Experiment 2, fish were given three injections of saline, 0.1
      microgram rbIGF-I/g, 4 microgram F/g, or 0.1 microgram rbIGF-I + 4 microgram F/g
      and sampled in FW 24 h after the last injection. IGF-I and F had additive
      stimulatory effects on Na+,K+-ATPase activity and alpha-subunit Na+,K+-ATPase
      mRNA levels in the gill. Injections of IGF-I and F alone and in combination
      increased Na+,K+-ATPase-immunoreactive (NKIR) cell number in the primary gill
      filament but had no effect on secondary lamellar NKIR cell number. NKIR cells
      were abundant in kidney tubules, pyloric ceca, and posterior intestine, but
      Na+,K+-ATPase enzyme activity was unaffected by treatment with F and/or IGF-I in
      these tissues. F but not rbIGF-I increased in vitro fluid transport capacity in
      the posterior intestine. In addition to confirming an overall SW-adaptive effect
      of rbIGF-I and F in FW-acclimated S. trutta, the study suggests the effect to be
      associated with stimulation of chloride cell development and Na+,K+-ATPase
      expression in the gill. The study indicates that the stimulatory effects of the
      two hormones on Na+,K+-ATPase expression are additive, highly organ specific, and
      restricted to the primary filament epithelium of the gill.

PMID- 10068496
TI  - Characterization of thyroid hormone 5'-monodeiodinase activity in the turtle
      (Trachemys scripta).
AB  - Thyroid hormone metabolism by 5'-monodeiodinase enzymes (5'MD) was characterized
      in peripheral tissues of the turtle, Trachemys scripta, and compared with
      activity measured in the rat. Based on differences in pH dependence, sensitivity
      to inhibitors, substrate affinity, and cofactor requirements, at least two types
      of enzyme activities have been identified in the turtle. A 5'MD activity was
      measured in liver and kidney microsomal fractions that exhibits inhibition by 2n
      propyl-6-thiouracil (PTU), a higher affinity for rT3 (Km = 2 microM) than for T4
      (Km = 6.5 microM), a low cofactor dependence, and a high pH optimum for T4
      metabolism. The characteristics of this turtle low affinity T4 activity
      correspond to the mammalian type I monodeiodinase. A second type of
      monodeiodinase (MD) activity that is less sensitive to PTU, has a higher affinity
      for T4 (Km = 1 nM), a higher cofactor requirement, and a lower pH optimum was
      colocalized with the first form. Both turtle MD activities remain active over a
      range of temperatures, allowing for activity at the preferred body temperature of
      this species (28 to 37 degrees C compared to the 37 degrees C optimum in the
      rat). Based on limited comparative data of MD systems from several fish and
      birds, the turtle most closely resembles avian species. Like birds, turtles
      possess a mammalian-like type I activity and have colocalized MD forms in the
      liver. However, the second turtle MD form (MDH) is not comparable to the
      mammalian or avian MDII-like activity. Analysis of the deiodinase products from
      both turtle MDs by high-performance liquid chromatography confirmed that the
      putative turtle MDI produces T3 from T4 as expected. The MDH produces rT3 from T4
      as does the mammalian type III form, but MDH has a wider tissue distribution
      (kidney, liver, pancreas, heart, ovary, and brain) and distinct enzyme kinetics.
      Moreover, MDH activity in the turtle kidney is 100-fold higher than in the liver,
      indicating that the kidney may play a critical role in the metabolism of thyroid
      hormones in the turtle; this high renal activity distinguishes the turtle from
      all other vertebrates studied.

PMID- 10068497
TI  - Cloning, in vitro expression, and novel phylogenetic classification of a channel
      catfish estrogen receptor.
AB  - We obtained two channel catfish estrogen receptor (ccER) cDNA from liver of
      female fish using RT-PCR. The two fragments were identical in sequence except
      that the smaller one had an out-of-frame deletion in the E domain, suggesting the
      existence of ccER splice variants. The larger fragment was used to screen a cDNA
      library from liver of a prepubescent female. A cDNA was obtained that encoded a
      581-amino-acid ER with a deduced molecular weight of 63.8 kDa. Extracts of COS-7
      cells transfected with ccER cDNA bound estrogen with high affinity (Kd = 4.7 nM)
      and specificity. Maximum parsimony and Neighbor Joining analyses were used to
      generate a phylogenetic classification of ccER on the basis of 18 full-length ER
      sequences. The tree suggested the existence of two major ER branches. One branch
      contained two clearly divergent clades which included all piscine ER (except
      Japanese eel ER) and all tetrapod ERalpha, respectively. The second major branch
      contained the eel ER and the mammalian ERbeta. The high degree of divergence
      between the eel ER and mammalian ERbeta suggested that they also represent
      distinct piscine and tetrapod ER. These data suggest that ERalpha and ERbeta are
      present throughout vertebrates and that these two major ER types evolved by
      duplication of an ancestral ER gene. Sequence alignments with other members of
      the nuclear hormone receptor superfamily indicated the presence of 8 amino acids
      in the E domain that align exclusively among ER. Four of these amino acids have
      not received prior research attention and their function is unknown. The novel
      finding of putative ER splice variants in a nonmammalian vertebrate and the novel
      phylogenetic classification of ER offer new perspectives in understanding the
      diversification and function of ER.

PMID- 10068498
TI  - Fish calcitonin genes: primitive bony fish genes have been conserved in some
      lower vertebrates.
AB  - Using the polymerase chain reaction method, we amplified calcitonin genes from
      the cDNA of the ultimobranchial glands or from the genomic DNA of the blood cells
      and liver of various fishes. The fishes examined were primitive bony fishes
      (lungfish, polypterus, sturgeon, and gar), 16 species of teleosts, and
      cartilaginous fishes (stingray). Sequenced calcitonin genes were compared among
      fishes and with those of reptiles and chickens. The similarity of the calcitonin
      genes was the highest between the reptile and chicken groups and the primitive
      bony fishes (sequence similarity of the nucleotides 81-90%). The values between
      teleosts and the primitive bony fishes were 70-81%, with the exception of eels.
      Eel calcitonin genes were very similar to those of primitive bony fishes (83
      88%). Stingray calcitonin genes were relatively more similar to those of the
      primitive bony fishes (74-78%) than to teleosts (63-73%). In goldfish and
      sardine, two types of calcitonin genes were found. We concluded that the genes of
      primitive bony fish are placed at a fundamental position in this hormone, at
      least among these vertebrates.

PMID- 10068499
TI  - The pulmonary neuroendocrine system and drainage of the fetal lung: effects of
      serotonin.
AB  - The neuroendocrine system of the lungs is maximally developed and activated at
      birth, but has no clear function. Here, one of its products, serotonin, was
      tested for an ability to stop lung fluid production or activate reabsorption.
      Lungs from fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro
      for 3 h; lung liquid production was monitored by a dye dilution method. Initial
      studies on 36 young fetuses (61 +/- 1 days of gestation) showed that untreated
      controls produced fluid at 1.17 +/- 0.23 ml.kg-1.h-1, with no significant change
      over 3 h (ANOVA; regression analysis); those given 10(-8) M serotonin during the
      middle hour showed no significant changes, but those given 5 x 10(-8), 10(-7),
      10(-6), or 10(-5) M serotonin reduced production significantly (P < 0.01 to P <
      0.0005). Responses were linear up to 10(-7) M (threshold, 10(-9) M) and then
      become maximal at 50% reduction. However, responses increased with age.
      Comparison of 40 fetuses divided into groups of 60-61 or 65-67 days of gestation
      showed a large and significant increase in responses in the older fetuses (P <
      0.01), where half the preparations reabsorbed fluid. Serotonin receptors were
      involved, since 10(-6) M cyproheptadine abolished responses (based on 24
      preparations). Amiloride-sensitive Na+ channels were involved, since 10(-6) M
      amiloride abolished responses (based on 24 preparations). These results, in
      combination with earlier results from somatostatin and dopamine, together with
      histochemical and clinical observations, strongly suggest that the neuroendocrine
      system of the lungs may find a function in clearing fluid from the lungs at time
      of birth.

PMID- 10068500
TI  - Molecular cloning of an estrogen receptor beta subtype from the goldfish,
      Carassius auratus.
AB  - The brain of many teleost fish species, including the goldfish Carassius auratus,
      expresses exceptionally high levels of cytochrome P450 aromatase (estrogen
      synthetase). To begin investigating the molecular and cellular targets of
      estrogen action in goldfish brain, a polymerase chain reaction (PCR) cloning
      strategy was used to isolate an estrogen receptor (ER) complementary DNA (cDNA).
      The 2283-bp cDNA isolated from goldfish liver encoded a protein of 568 amino
      acids (aa) with an estimated molecular weight of 63,539. The goldfish ER had high
      overall sequence identity when compared to other vertebrate ER sequences: eel
      (64%), human beta subtype (59%), human alpha subtype (46%), medaka (46%), and
      rainbow trout (47%). The highest degree of conservation was seen in the DNA
      binding (94-100%) and ligand-binding (67-79%) domains. Phylogenetic analysis of
      the ER gene family indicated that the goldfish and eel ER are most closely
      related to mammalian ERbeta subtypes, whereas previously identified fish,
      amphibian, and avian ER forms cluster separately with mammalian ERalpha subtypes.
      Using the goldfish ER cDNA (here designated gfERbeta), multiple mRNA species (3.1
      8.6 kb) were detected by Northern blot analysis in goldfish liver and ovary but
      expression was below detection in brain. Using reverse transcription-PCR
      analysis, gfERbeta mRNA was detected in forebrain, mid/hindbrain, pituitary,
      retina, liver, ovary, and testis. Further studies are required to determine
      whether an additional ERalpha subtype is present in the goldfish and whether
      ERalpha or ERbeta forms have evolutionary precedence in vertebrates.

PMID- 10068501
TI  - Several isoforms of locustatachykinins may be involved in cyclic AMP-mediated
      release of adipokinetic hormones from the locust Corpora cardiaca.
AB  - Four locustatachykinins (LomTK I-IV) were identified in about equal amounts in
      extracts of corpora cardiaca of locusts, using reverse-phase high-performance
      liquid chromatography and radioimmunoassay with synthetic LomTK I-IV as
      standards. Brain extracts also contained the four isoforms in roughly equimolar
      concentrations. Retrograde tracing of the nervi corporis cardiaci II (NCC II) in
      vitro with Lucifer yellow in combination with LomTK immunocytochemistry revealed
      that about half of the secretomotor neurons in the lateral part of the
      protocerebrum projecting into the glandular lobe of the corpora cardiaca (CCG)
      contain LomTK-immunoreactive material. Since the four LomTKs are present in the
      CCG, these four or five neurons in each hemisphere are likely to contain
      colocalized LomTK I-IV. The role of two of the LomTKs in the regulation of the
      release of adipokinetic hormones (AKHs) from the adipokinetic cells in the CCG in
      the locust was investigated. Experiments performed in vitro showed that LomTK I
      and II induced release of AKH in a dose-dependent manner. These peptides also
      rapidly and transiently elevated the cyclic AMP-content of the CCG. The peak
      level of cyclic AMP occurred about 45 seconds after stimulation with LomTK. These
      results support the proposal that LomTKs are involved in controlling the release
      of the adipokinetic hormones and suggest that all LomTK isoforms may participate
      in this cyclic AMP-mediated event.

PMID- 10068502
TI  - Growth hormone (GH) and gonadotropin subunit gene expression and pituitary and
      plasma changes during spermatogenesis and oogenesis in rainbow trout
      (Oncorhynchus mykiss).
AB  - In order to evaluate potential interactions between somatotropic and gonadotropic
      axes in rainbow trout (Oncorhynchus mykiss), changes in pituitary content of the
      specific messenger RNA of growth hormone (GH) and gonadotropin (GTH) alpha- and
      beta-subunits were studied during gametogenesis with respect to pituitary and
      plasma hormone concentrations. Quantitative analyses of mRNA and hormones were
      performed by dot blot hybridization and homologous RIA on individual fish
      according to stage of spermatogenesis and oogenesis. All transcripts were
      detectable in 9-month-old immature fish. GH, GTH IIbeta, and GTH alpha increased
      moderately throughout most of gametogenesis and then more dramatically at
      spermiation and during the periovulatory period. GTH Ibeta mRNA increased first
      from stage I to V in males and more abruptly at spermiation, while in females GTH
      Ibeta transcripts increased first during early vitellogenesis and again around
      ovulation. Pituitary GH absolute content (microgram/pituitary, not normalized
      with body weight) increased slowly during gametogenesis and more abruptly in
      males during spermiation. In the pituitary of previtellogenic females and
      immature males, GTH I beta peptide contents were 80- to 500-fold higher than GTH
      II beta peptide contents. GTH I contents rose regularly during the initial phases
      of vitellogenesis and spermatogenesis and then more abruptly in the final stages
      of gonadal maturation, while GTH II contents show a dramatic elevation during
      final oocyte growth and maturation, in postovulated females, and during
      spermiogenesis and spermiation in males. Blood plasma GTH II concentrations were
      undetectable in most gonadal stages, but were elevated during spermiogenesis and
      spermiation and during oocyte maturation and postovulation. In contrast, plasma
      GTH I was already high ( approximately 2 ng/ml) in fish with immature gonads,
      significantly increased at the beginning of spermatogonial proliferation, and
      then increased again between stages III and VI to reach maximal levels (
      approximately 9 ng/ml) toward the end of sperm cell differentiation, but
      decreased at spermiation. In females, plasma GTH I rose strongly for the first
      time up to early exogenous vitellogenesis, decreased during most exogenous
      vitellogenesis, and increased again around ovulation. Our data revealed that
      patterns of relative abundance of GTH Ibeta mRNA and pituitary and plasma GTH I
      were similar, but not the GTH II patterns, suggesting differential regulation
      between these two hormones at the transcriptional and posttranscriptional levels.
      Pituitary and plasma GH changes could not be related to sexual maturation, and
      only a weak relationship was observed between GH and gonadotropin patterns,
      demonstrating that no simple connection exists between somatotropic and
      gonadotropic axes at the pituitary level during gametogenesis.

PMID- 10068503
TI  - Sex reversal effects of environmentally relevant xenobiotic concentrations on the
      red-eared slider turtle, a species with temperature-dependent sex determination.
AB  - Xenobiotics suspected of being estrogenic-the PCB aroclor 1242 and the pesticides
      toxaphene, dieldrin, p,p'-DDD, cis-Nonachlor, trans-Nonachlor, p,p'-DDE, and
      chlordane-were examined for their ability to override a male-producing incubation
      temperature and result in female hatchlings in the red-eared slider, a turtle
      with temperature-dependent sex determination. Compounds were assayed in the
      environmentally relevant concentrations detected in alligator eggs from Lake
      Apopka, Florida, singly, in concert with one another, and with estradiol.
      Compounds assayed alone and resulting in significant sex reversal were trans
      Nonachlor, cis-Nonachlor, aroclor 1242, p,p'-DDE, and chlordane. When
      administered with estradiol, only one of the compounds, chlordane, caused sex
      reversal at significant levels. When applied together, however, the eight
      compounds assayed resulted in significant sex reversal.

PMID- 10068504
TI  - Seasonal changes in mRNA levels of gonadotropin and thyrotropin subunits in the
      goldfish, Carassius auratus.
AB  - Seasonal changes in the mRNA levels of glycoprotein alpha, gonadotropin (GTH)
      Ibeta and IIbeta, and thyrotropin (thyroid-stimulating hormone (TSH)) beta
      subunits in the pituitary of goldfish were quantified by Northern blot analysis
      and laser densitometry. Reproductive development and thyroid activity were
      monitored by measuring gonadosomatic index, plasma GTH II, testosterone (T),
      estradiol, 11-ketotestosterone, and thyroid hormones (T4 and T3). Plasma GTH II
      and steroids showed characteristic increases, while plasma thyroid hormones
      levels, in general, decreased in association with the reproductive period. In
      females, the mRNA levels of the alpha, GTH Ibeta, and GTH IIbeta subunits
      increased synchronously during early spawning period (April) and then decreased
      during ovarian regression (August). In males, the levels of the alpha and GTH
      IIbeta subunits showed changes similar to those in females, but the GTH Ibeta
      mRNA levels showed only a small increase during the late spawning period (May).
      In both sexes, TSHbeta mRNA levels were high during winter to early spring
      (February and April) and low during late spring to summer (May and August). These
      results suggest that in goldfish the gonadotropins may be synthesized
      synchronously in order for asynchronous gametogenesis to take place.
      Additionally, the data suggest a negative feedback relationship between synthesis
      of the TSHbeta subunit and the thyroid hormones.

PMID- 10068505
TI  - Effects of ambient temperature on photo-induced prolactin secretion in three
      subspecies of white-crowned sparrow, Zonotrichia leucophrys.
AB  - We tested the effects of naturally relevant ambient temperatures (5, 20, and 30
      degrees C) on photoinduced prolactin (PRL) secretion in three subspecies of white
      crowned sparrow, Zonotrichia leucophrys. In all three subspecies, transfer from
      short to long days triggered an increase in plasma PRL typical of an avian
      seasonal breeder. In Z. l. gambelii, which breeds at high latitudes, temperature
      does not affect the rate of photoinduced gonadal maturation or luteinizing
      hormone (LH) secretion. In this subspecies, we found that changes in plasma PRL
      concentrations were similar in all temperature treatments. In Z. l. pugetensis,
      which breeds in the Pacific Northwest, high temperatures accelerate gonadal
      development in females but not males and does not affect LH secretion. In this
      subspecies, we found that like gonadal growth, photoinduced changes in PRL
      secretion in Z. l. pugetensis vary with ambient temperature in females but not
      males. In Z. l. oriantha, which breeds in alpine regions of the West, both males
      and females respond to temperature cues by modulating gonadal growth but not LH
      secretion. We found in Z. l. oriantha that ambient temperature affects PRL
      secretion in both sexes. These results suggest that PRL may be involved in the
      transduction of ambient temperature cues used to time reproductive development
      and the termination of seasonal breeding. Alternatively, temperature-mediated
      differences in plasma PRL may be a result rather than a cause of differences in
      gonadal development, since sex steroids affect PRL secretion in some species.

PMID- 10068506
TI  - Effect of season and photoperiod on FSH in male great tits.
AB  - The present study investigated (1) the photoperiodic threshold for an increase in
      FSH and LH secretion in male great tits (Parus major) from south Sweden and (2)
      seasonal changes in FSH secretion patterns in short day (SD; 8 L:16 D) and long
      day (LD; 20 L:4 D) exposed great tits. When fully photosensitive great tits were
      exposed to a simulated vernal increase in day lengths plasma levels of FSH
      started to rise at a shorter day length (10.5 h) than did LH (11 h). Once the
      photoperiodic threshold was exceeded FSH levels increased slowly, but
      continuously, and reached maximum levels when day lengths had reached 13-14 h,
      whereas LH levels rose to maximum levels more or less immediately. Great tits
      break photorefractoriness in September. Exposing sham-operated and castrated
      great tits to SD or LD in October and February resulted in clear seasonal
      differences in their FSH cycles. At both times the great tits responded to
      castration and exposure to long days. However, castration and photoperiodic FSH
      responses were not only more rapid in February, but also of a higher magnitude.

PMID- 10068507
TI  - Effects of photoperiod on the cessation of growth during autumn in male red deer
      and growth hormone and insulin-like growth factor-I secretion.
AB  - Male red deer undergo seasonal cycles of food intake and growth rate, which are
      high during spring and low during winter, despite high quality food ad libitum.
      Hormonal profiles during the cessation of growth in autumn and the potential role
      of photoperiod in the timing of the observed changes have been investigated.
      Whether this seasonal decrease in growth affected the response of GH and IGF-I to
      fasting was also examined. Two groups of six male 1-year-old red deer were
      exposed to different photoperiods after the summer solstice. One group (C) was
      given a simulated natural photoperiod while the other group (SS) was maintained
      on a summer solstice photoperiod (16L:8D). GH was measured in blood collected
      continuously and divided into pools every 5 min for 24 h in the fed state and
      after a 48-h fast on two occasions; the first was in November before photoperiod
      manipulation began and the second was in April approximately 16 weeks after
      initiating treatments. IGF-I, prolactin, and testosterone were measured in weekly
      samples. Individual live weight and group food intake were also measured each
      week. The normal growth pattern seen in the C group was delayed in the SS group.
      Thus, from 7 March until the second GH sampling on 11 April the live weight of
      deer in group C fell; in contrast, deer in group SS continued to grow (-43 vs 186
      g/day s.e.d. = 65.5, P < 0. 01). Food intake changes reflected the pattern of
      growth in both groups. Mean GH (P < 0.05), GH pulse amplitude (P < 0.01), and IGF
      I (P < 0.001) declined in both groups from November to April. This decline was
      more marked in group C and in April these parameters were all lower in group C
      than in group SS (GH, P < 0.05; IGF-1, P < 0.01). Prolactin levels in April were
      also lower in group C than in group SS (P < 0.01); testosterone was not affected
      by treatment. Fasting increased mean GH and GH pulse amplitude in both groups in
      November (P < 0.05). In April, the fasting response differed between the groups.
      In group C, mean GH, pulse amplitude, and pulse frequency were all greater in the
      fasted state than in the fed state (P < 0.05), while in group SS there were no
      significant differences (P > 0.05). IGF-I was lower in the fasted state than in
      the fed state at both sampling dates (P < 0.001). The seasonal decline in food
      intake and growth is associated with decreased GH, IGF-I, and prolactin
      concentrations, and increased testosterone and the GH response associated with
      fasting. All these changes except those of testosterone were delayed or reduced
      by continued exposure to a summer solstice photoperiod in autumn. The decreased
      photoperiod in autumn may thus influence the normal timing of the seasonal growth
      cycle.

PMID- 10068508
TI  - Announcement 

PMID- 10068509
TI  - Maturational changes in gene expression for adenine nucleotide translocator
      isoforms and betaF1-ATPase in rabbit heart.
AB  - Maturational changes in myocardial respiratory control have been related to
      postnatal accumulation of adenine nucleotide translocator (ANT) in the inner
      mitochondrial membrane. Alternatively alterations in relative isoform
      distribution for this nuclear-encoded gene during myocardial maturation might be
      responsible for changing the kinetics of respiratory control. Rabbit hearts were
      analyzed for adenine nucleotide translocator isoform (ANT1, ANT2, ANT3) gene
      expression and distribution at four ages (fetal, 29/31 days of gestation; 1 h
      postnatal; 9 days postnatal; and 3-4 months postnatal). Transcript levels for the
      coordinately expressed betaF1-ATPase were also examined in these hearts. These
      studies demonstrated that mRNA expression for ANT1 in coordination with betaF1
      ATPase increased substantially after 9 days of age in rabbit hearts. Expression
      of the minor isoform ANT3 parallels ANT1, though no change in expression of the
      kidney-specific isoform ANT2 occurs in heart during this developmental period.
      Previous work has demonstrated that ANT protein accumulation is closely
      coordinated with mRNA expression for ANT1. These results support previous
      studies, which indicate that the operational mode of myocardial respiratory
      control depends on adenine nucleotide mRNA expression. Changes in relative
      adenine nucleotide translocator isoform distribution do occur during fetal to
      mature transition and may contribute to observed changes in the mode of
      respiratory control.

PMID- 10068510
TI  - Mechanism of biotin responsiveness in biotin-responsive multiple carboxylase
      deficiency.
AB  - Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin
      dependent carboxylases found in humans. A deficiency in HCS results in biotin
      responsive multiple carboxylase deficiency. We have evaluated the biotin
      responsiveness associated with six missense mutations previously identified in
      affected patients by expression of plasmids containing the mutated HCS in an
      Escherichia coli strain mutated in the corresponding BirA gene. We demonstrate
      that the mutations identified in the MCD patients are indeed responsible for
      their reduced HCS activity. Four of the mutations, clustering in the putative
      biotin binding domain as deduced from the structure of the E. coli enzyme, are
      consistent with an explanation for biotin responsiveness based on altered
      affinity for biotin. The remaining mutations, located outside the biotin binding
      region, were associated with a more limited biotin responsiveness that may be
      explained by the degree of residual enzyme activity present. The data suggest
      that the concentration of circulating biotin is as low as 100 times below the Km
      of the enzyme, so that any increase in biotin concentration through dietary
      supplementation would result in saturation of the available mutant enzyme. We
      suggest that these alternative explanations are sufficient to account for the
      apparent universality of biotin responsiveness in biotin responsive multiple
      carboxylase deficiency.

PMID- 10068511
TI  - Peroxisomal very long chain fatty acid beta-oxidation activity is determined by
      the level of adrenodeukodystrophy protein (ALDP) expression.
AB  - Impaired peroxisomal beta-oxidation of saturated very long chain fatty acids
      (VLCFA, >/=C22:0) results in increased VLCFA levels in the tissues and body
      fluids of patients with disorders of peroxisomal biogenesis (i.e., Zellweger
      syndrome and neonatal adrenoleukodystrophy) and single peroxisomal protein
      defects (i.e., X-linked adrenoleukodystrophy (X-ALD) and acyl-CoA oxidase
      deficiency). We show that SV40T transformation also results in impaired
      peroxisomal beta-oxidation and VLCFA accumulation despite the presence of
      abundant peroxisomes. To explore the mechanism responsible for this observation,
      we have examined expression of key components of peroxisomal VLCFA beta
      oxidation. We found that expression of both acyl-CoA oxidase, the rate limiting
      enzyme of peroxisomal VLCFA beta-oxidation and the adrenoleukodystrophy protein
      (ALDP), the defective gene product in X-ALD, are reduced after SV40T
      transformation. Surprisingly, ALDP overexpression by itself restores peroxisomal
      VLCFA beta-oxidation in SV40T-transformed control and X-ALD cells. These results
      demonstrate that ALDP is a fundamental component in VLCFA peroxisomal beta
      oxidation and may serve as a "gatekeeper" for VLCFA homeostasis.

PMID- 10068512
TI  - Effects of dystrophin isoforms on signal transduction through neural retina:
      genotype-phenotype analysis of duchenne muscular dystrophy mouse mutants.
AB  - Duchenne and Becker muscular dystrophy patients have mutations in the dystrophin
      gene. Most show reduced b-wave amplitudes in the dark-adapted electroretinogram
      (ERG). We studied normal C57BL/6J mice and five X-linked muscular dystrophy
      strains with different dystrophin mutations to determine whether the location of
      the mutation within the gene affects the mouse ERG and to correlate such effects
      with dystrophin isoform expression. Amplitudes and implicit times were measured
      for a-waves, b-waves, and digitally filtered oscillatory potentials. mdx and
      mdxCv5 mice, with mutations near the amino terminus and lacking expression of
      Dp427, had ERGs similar to those of C57BL/6J mice. mdxCv2 and mdxCv4 mice, with
      mutations in the center of dystrophin and who do not express isoforms Dp427,
      Dp260, or Dp140 (mdxCv4), had increased b-wave and oscillatory potential implicit
      times. mdxCv3 mice, with a mutation near the carboxy terminus resulting in
      deficiency of all dystrophin isoforms, had increased b-wave and oscillatory
      potential implicit times and reduced scotopic b-wave amplitudes. Fitting the a
      wave data to a transduction activation phase mathematical model showed normal
      responses for all phenotypes, suggesting that the b-wave delays are due to
      defects beyond the rod outer segment, most likely at the rod to on-bipolar cell
      synapse. The variation in the ERG phenotype with the position of the dystrophin
      gene mutation suggests that there are different contributions by each isoform to
      retinal electrophysiology. Although Dp427 and Dp140 isoforms do not appear to be
      important contributors to the ERG, lack of Dp260 and possibly Dp71 isoforms is
      associated with an abnormal ERG.

PMID- 10068513
TI  - Identification and detection of the common 65-kb deletion breakpoint in the
      nephropathic cystinosis gene (CTNS).
AB  - The most common mutation in the cystinosis gene, CTNS, is a 65-kb deletion
      thought to have originated in Germany. Although homozygotes for this deletion are
      detectable by the absence of the D17S829 polymorphic marker, no method exists to
      identify heterozygotes. We identified the 65-kb deletion breakpoints and used
      flanking PCR primers to amplify a 423-bp fragment present only in the deletion
      alleles. Using this method, we determined that 121 of 216 (56%) cystinosis
      alleles examined bore the 65-kb deletion. We found no non-Europeans with the
      deletion, and the deletion size and breakpoints appeared identical in all
      patients studied, supporting the concept of a founder effect. The addition of
      D17S829 primers (266 bp apart) to the PCR created a multiplex PCR system useful
      for diagnosing cystinosis patients homozygous and heterozygous for the 65-kb
      deletion.

PMID- 10068514
TI  - Complementation studies in human and feline Niemann-Pick type C disease.
AB  - Complementation studies were performed to determine if the gene responsible for
      the major form of human Niemann-Pick type C disease (NPC) and a feline model of
      NPC are orthologous. Cell fusions between human NPC and feline NPC fibroblasts
      were conducted to assess whether the multinucleated heterokaryons that were
      formed showed a reversal of the NPC phenotype. Cultured fibroblasts from NPC
      affected humans and NPC-affected cats were hybridized and then analyzed for
      complementation by challenging the cells with low-density lipoprotein (LDL) and
      subsequently staining with the fluorescent antibiotic filipin to visualize any
      abnormal accumulation of unesterified cholesterol. All of the multinucleated
      cells formed from these fusions retained the NPC staining phenotype, indicating
      an absence of complementation and suggesting that the underlying defect in the
      major form of human NPC and this feline model of NPC involve orthologous genes.

PMID- 10068515
TI  - Sequence comparisons reveal two classes of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase.
AB  - Both in eukaryotes and in archaebacteria the enzyme 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase (E.C. 1.1. 1.34) is known to catalyze an early
      reaction unique to isoprenoid biosynthesis. In humans, the HMG-CoA reductase
      reaction is rate-limiting for the biosynthesis of cholesterol and therefore
      constitutes a prime target of drugs that reduce serum cholesterol levels. Recent
      advances in genome sequencing that permitted comparison of 50 HMG-CoA reductase
      sequences has revealed two previously unsuspected classes of this enzyme. Based
      on sequence and phylogenetic considerations, we propose the catalytic domain of
      the human enzyme and the enzyme from Pseudomonas mevalonii as the canonical
      sequences for Class I and Class II HMG-CoA reductases, respectively. These
      sequence comparisons have revealed, in addition, that certain true bacteria,
      including several human pathogens, probably synthesize isoprenoids by reactions
      analogous to those of eukaryotes and that there therefore exist two distinct
      pathways for isoprenoid biogenesis in true bacteria.

PMID- 10068516
TI  - Accurate DNA-based diagnostic and carrier testing for X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is a serious and often fatal disorder, affecting
      the white matter of the nervous system, the adrenal cortex, and the testis. The
      gene mutated in X-ALD encodes a peroxisomal membrane protein, ALDP. The presence
      of very long chain fatty acids in plasma is highly diagnostic for affected males
      and carrier females, but exclusion of carrier status biochemically is unreliable.
      Molecular analysis of the X-ALD gene has the potential to either identify or rule
      out carrier status accurately, but is complicated by the existence of autosomal
      paralogs. We have developed and validated a robust DNA diagnostic test for this
      disorder involving nonnested genomic amplification of the X-ALD gene, followed by
      fluorescent dye-primer sequencing and analysis. This protocol provides a highly
      reliable means of determining carrier status in women at risk for transmitting X
      ALD and is applicable to a clinical diagnostic laboratory.

PMID- 10068517
TI  - Glucocorticoid resistance in premature pubarche and adolescent hyperandrogenism.
AB  - To determine whether glucocorticoid resistance due to mutations in the
      glucocorticoid receptor (GRL) gene is associated with premature pubarche,
      hirsutism, or oligo/amenorrhea, we performed single-strand conformational
      polymorphism analysis of genomic DNA obtained from 25 children and 16 adolescent
      girls referred for the evaluation of premature pubarche, hirsutism, or
      oligo/amenorrhea. A missense mutation, N363S, and a presumed polymorphism in the
      3'-UTR of exon 9alpha were identified. We conclude that glucocorticoid resistance
      due to GRL mutations is an infrequent cause of mild hyperandrogenism.

PMID- 10068518
TI  - Ischemia-reperfusion protects the rat small intestine against subsequent injury.
AB  - BACKGROUND: It has been suggested that multiple sublethal insults are commonly
      associated with the development of multiple organ failure (MOF). The gut is
      considered to be pivotal in the pathogenesis of MOF. This study investigated the
      effects of repeated ischemia-reperfusion of the rat small intestine. METHODS:
      Groups of rats underwent 30 min of superior mesenteric artery occlusion or sham
      operation followed by 24 h of reperfusion. They then received an additional 30
      min of superior mesenteric artery occlusion and 2 h of reperfusion or sham
      operation. Small intestine was examined for mucosal injury, neutrophil
      infiltration, goblet cell number, and generation of the eicosanoids,
      prostaglandin E2, and leukotriene B4. Activation of neutrophils was assessed in
      systemic venous blood. RESULTS: Animals subjected to two insults of ischemia
      reperfusion demonstrated significantly less mucosal injury than animals
      undergoing one episode of ischemia and 2 h of reperfusion, despite increased
      neutrophil infiltration, leukotriene B4, and activated systemic neutrophils.
      Goblet cell number was elevated in animals 24 h after the first ischemia
      reperfusion insult and remained enhanced after the second episode of ischemia
      reperfusion. CONCLUSIONS: The initial episode of ischemia-reperfusion caused an
      adaptive response associated with cytoarchitectural preservation following the
      subsequent insult. Increased mucus production was associated with mucosal
      protection. Nevertheless, repeated ischemia-reperfusion potentiated the local
      inflammatory response and the systemic activation of neutrophils.

PMID- 10068519
TI  - Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold
      preserved warm-reperfused rat livers.
AB  - BACKGROUND/AIM: A mechanism suggested to cause injury to preserved organs is the
      generation of oxygen free radicals. Lipid peroxidation is one of the biological
      damages caused by oxygen free radicals. It is our aim to investigate whether
      magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals
      and improves the viability of cold-preserved warm-reperfused rat livers.
      MATERIALS AND METHODS: In vitro lipid peroxidation was induced in rat hepatic
      mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid
      peroxidation was measured with oxygen consumption and malondialdehyde (MDA)
      formation. Subsequently, we preserved and reperfused rat livers in preservation
      solutions that contained magnolol. The hepatic enzymes and liver MDA were
      measured to assess the protective effect of magnolol on isolated rat livers.
      RESULTS: In rat hepatic mitochondria, magnolol was 470 times more potent than
      alpha-tocopherol in inhibiting oxygen consumption and 340 times more potent than
      alpha-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's
      lactate solution had a protective effect, in terms of MDA formation and leakage
      of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition
      of magnolol to University of Wisconsin (UW) solution, a widely used preservation
      solution, did not modify the effect of this solution on isolated liver tissues.
      CONCLUSIONS: We conclude that magnolol is an effective antioxidant and suppresses
      lipid peroxidation in rat liver mitochondria and can be used as a rinsing
      solution in protecting transplanted organs from lipid peroxidation during
      reperfusion, especially for those organs not preserved with UW solution.

PMID- 10068520
TI  - Oral administration of L-arginine reduces intimal hyperplasia in balloon-injured
      rat carotid arteries.
AB  - Endogenous nitric oxide (NO) is produced from L-arginine by NO synthase. We
      evaluated the effect of oral administration of L-arginine on intimal hyperplasia
      in balloon-injured rat carotid arteries. Thirty Sprague-Dawley rats underwent
      balloon denudation on the left common carotid artery. Fifteen rats were treated
      with L-arginine in drinking water (2.5 mg/mL) two days before injury and were
      continued for 2 weeks. Another 15 rats served as controls. All animals survived
      without complications or body weight loss. In the treated group, daily intake of
      L-arginine was 170 +/- 43 mg/day. Plasma arginine levels were 130 +/- 32
      micromol/L prior to L-arginine intake, 165 +/- 42 micromol/L at the day of
      injury, and 162 +/- 26 micromol/L at sacrifice. Intimal hyperplasia developed in
      all balloon-injured arteries in both control and L-arginine-treated animals.
      However, L-arginine-treated animals showed a 65% reduction of the intima/media
      area ratio and a 26% reduction of the intimal cell proliferation compared with
      control animals. These data indicate that adequate amounts of L-arginine were
      ingested by the rats and that oral administration of L-arginine significantly
      reduced intimal hyperplasia of balloon-injured arteries without any detectable
      toxicity.

PMID- 10068521
TI  - Reduced capacity to inhibit elastase in abdominal aortic aneurysm.
AB  - BACKGROUND: Loss of elastin in the aortic wall is an early event in abdominal
      aortic aneurysm (AAA). An imbalance in the protease-antiprotease system is
      proposed to be one of the factors that promote connective tissue destruction. We
      hypothesize that plasma from AAA patients will have a reduced inhibitory capacity
      in comparison to normal controls. MATERIALS AND METHODS: Using an assay we
      developed, plasma (10 microliters), collected from AAA patients (n = 14) and
      normal controls (n = 13), was added to the elastase inhibition assay containing
      succinylated elastin substrate. The reaction was initiated with 13.9 units
      porcine pancreatic elastase (PPE). Elastase activity in the presence and absence
      of plasma was compared. Plasma elastase was also determined using the Merck PMN
      elastase kit. RESULTS: The relative activity of exogenous elastase (%) in the
      presence of AAA plasma (n = 14, mean age 73.4 years +/- 1.7 SEM) was 42.59% +/-
      4.3 SEM, while that in the presence of control plasma (n = 13, mean age 73.9
      years +/- 2.1 SEM) was 10.23% +/- 2.1 SEM (P < 0.0001). Analysis of plasma
      elastase (microgram/L) indicated that there was no significant difference between
      normal (n = 9, 207.33 microgram/L +/- 58.67 SEM) and AAA (n = 9, 145.34
      microgram/L +/- 29.54 SEM) (P = 0.359). CONCLUSION: There is a significant
      reduction in the plasma inhibitory capacity of elastase in AAA patients in
      comparison to normal controls, though plasma elastase level was not significantly
      different. The data presented here give experimental evidence to the protease
      antiprotease imbalance in AAA patient plasma and may lead to the development of a
      measurable parameter to monitor AAA.

PMID- 10068522
TI  - Remodeling of peritoneal-like structures by mesothelial cells: its role in
      peritoneal healing.
AB  - BACKGROUND: Intraabdominal adhesions are a common complication following
      laparotomy. Since the exact mechanisms involved in this processes are unknown we
      have analyzed in vitro the role of mesothelial cells in peritoneal healing.
      MATERIAL AND METHODS: Human mesothelial cells from omental tissue were cultivated
      for 2 weeks in a three-dimensional culture either on or in a collagen type I
      matrix. The effects of blood and collagen matrix were analyzed by exposing
      mesothelial cells to an overlying blood clot, simulating intraperitoneal
      bleeding, or a second collagen layer. The production of collagen types III and
      IV, fibronectin, and laminin was analyzed with immunohistochemical methods.
      RESULTS: Mesothelial cells grown on a collagen matrix formed a monolayer of flat
      or cobblestone-like cells whereas those cultivated in a collagen matrix exhibited
      spindle-like morphology. Mesothelial cells failed to grow into an overlying
      collagen matrix, but did grow into a blood clot, emphasizing a potential role of
      blood clots in peritoneal adhesion formation. Independent of the culture systems
      mesothelial cells produced collagen type III, fibronectin, and laminin but not
      collagen type IV. CONCLUSIONS: Our experiments demonstrate remodeling of
      peritoneal-like structures by mesothelial cells in a three-dimensional culture
      reflecting their putative role in the reepithelialization after serosal defects,
      and also in the formation of peritoneal adhesions.

PMID- 10068523
TI  - Protective effects of ulinastatin against ischemia-reperfusion injury.
AB  - We investigated the protective effect of urinary trypsin inhibitor (ulinastatin:
      UTI) in vitro, in relation to the neutrophil activity in hepatic
      ischemia/reperfusion (I/R) injury. The rat liver was removed and preserved in
      cold Ringer's lactate solution for 60 min, followed by 120 min of reperfusion
      with oxygenated perfusate. The rats were divided into four groups (n = 8 in each
      group). The livers were perfused with Krebs-Henseleit (K-H) solution containing
      no additives in group 1, 50,000 U/kg of UTI in group 2, 3.5 x 10(6) of
      neutrophils in group 3, and both neutrophils and UTI in group 4. In group 3, the
      AST and ALT levels were always higher than those in other three groups at any
      point evaluated (P < 0.01) and the LDH levels were observed to be significantly
      higher than those in other three groups at 0, 5, 10, 60, and 90 min after
      reperfusion (P < 0. 01). These increase were suppressed by additional
      pretreatment with UTI in group 4. The bile flow during reperfusion was
      significantly suppressed in group 3 compared to that of group 4, at both 30 (P <
      0. 01) and 60 (P < 0.05) min after reperfusion. The MPO activity after
      reperfusion in group 3 also significantly increased compared to other three
      groups (P < 0.01). These data thus suggest that UTI ameliorated the
      ischemia/reperfusion injury in vitro by inhibiting of neutrophil accumulation in
      the postischemic liver.

PMID- 10068524
TI  - Effect of cigarette smoke on endothelial regeneration in vivo and nitric oxide
      levels.
AB  - BACKGROUND: Cigarette smoking accelerates atherosclerosis and restenosis after
      vascular reconstruction. The mechanisms by which smoking alters vessel structure
      after injury are unclear. This study examined the effects of cigarette smoking on
      endothelial regeneration, an important component of arterial remodeling.
      MATERIALS AND METHODS: Adult male rats were subjected to balloon injury of the
      thoracic aorta and exposed to mainstream cigarette smoke via a Griffith-type
      smoking machine for 2 weeks. Control groups included rats which were restrained
      in the machine but not smoked and a group not utilizing the machine. Aortic
      reendothelialization was determined using Evan's blue staining of the arterial
      surface. Serum levels of nitric oxide were measured to determine if smoke
      exposure altered this potential endothelial cell mitogen. RESULTS: Cigarette
      smoking increased aortic endothelial regeneration (78.4 +/- 4.6% vs 59.2 +/-
      2.1%, P < 0.05) and was associated with an increase in serum nitric oxide level
      (59.9 +/- 7. 1 microM vs 28.5 +/- 1.8 microM, P < 0.05). Daily restraint alone in
      the smoking machine had no effect on endothelial regeneration. CONCLUSIONS: This
      is the first report on the effects of smoking on endothelial regeneration and
      demonstrates that smoking increases reendothelialization after large vessel
      injury and serum levels of nitric oxide, an EC mitogen.

PMID- 10068525
TI  - Complement component C3 production in IL-1beta-stimulated human intestinal
      epithelial cells is blocked by NF-kappaB inhibitors and by transfection with ser
      32/36 mutant IkappaBalpha.
AB  - BACKGROUND: Recent studies suggest that interleukin-1beta (IL-1beta) stimulates
      the production of the acute phase protein complement component C3 in human
      intestinal epithelial cells. The transcription factor NF-kappaB activates
      different genes involved in the response to cytokines. It is not known if IL
      1beta-induced C3 production in the enterocyte is regulated by NF-kappaB.
      MATERIALS AND METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell
      line, were treated with one of the NF-kappaB inhibitors, tosyl-lys
      chloromethylketone (TLCK), genistein, or pyrrolidine dithiocarbamate (PDTC), or
      with N-acetyl-leu-leu-norleucinal (LLnL), a proteasome inhibitor known to block
      the degradation of Ikappabeta, the cytosolic inhibitor of NF-kappaB. Following
      this treatment, the Caco-2 cells were stimulated with IL-1beta, and C3 levels in
      the culture medium were measured after 24 h by ELISA. C3 mRNA levels were
      determined after 4 h by Northern blot analysis. In other experiments, Caco-2
      cells were transfected with a mutant IkappaBalpha in which serines 32 and 36 were
      substituted by alanine. This mutation prevents IkBalpha phosphorylation and
      subsequent NF-kappaB nuclear translocation. After transfection, the cells were
      stimulated with IL-1beta, and C3 levels in the culture medium were measured after
      24 h. Cytosolic IkappaBalpha was determined by Western blot analysis. RESULTS:
      TLCK, genistein, and LLnL each inhibited IL-1beta-induced C3 production in a dose
      dependent fashion. These responses were associated with decreased C3 mRNA levels.
      In contrast, PDTC did not influence C3 production or C3 mRNA in the Caco-2 cells.
      Transfection of the Caco-2 cells with the Ser 32/36 mutant IkBalpha resulted in
      maintained IkappaBalpha levels and decreased IL-beta-induced C3 production.
      CONCLUSIONS: IL-1beta-stimulated C3 production in the enterocyte may be regulated
      by NF-kappaB.

PMID- 10068526
TI  - Continuous dose furosemide as a therapeutic approach to acute respiratory
      distress syndrome (ARDS).
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is seen in a variety of
      clinical settings in critically ill patients. ARDS has been defined as a clinical
      syndrome characterized by progressive hypoxemia, tachypnea, and generalized
      patchy bilateral pulmonary infiltrates in the absence of cardiac failure.
      Furosemide has been shown to improve pulmonary gas exchange and intrapulmonary
      shunt in animal models of ARDS by preferential perfusion of nonedematous lung
      units. We hypothesized that continuous dose furosemide would improve lung injury
      during resuscitation from oleic acid-induced lung injury in canines. METHODS: Ten
      mongrel dogs were anesthetized and given intravenous oleic acid (0.1 mg/kg) to
      induce lung injury. Once lung injury was established (2 h) the control animals (n
      = 6) were continued on standard supportive therapy, and the study animals (n = 4)
      were started on continuous dose furosemide at 0.2 mg/kg/h. Cardiac filling
      pressures were maintained in all animals by infusion of isotonic saline solution.
      Data collected included lung injury score (LIS), cardiac index (CI), stroke
      volume index (SVI), pulmonary capillary wedge pressure (PCWP), urine output (UO),
      volume of resuscitation (VR), and pulmonary shunt fraction (Qs/Qt). Data were
      collected at baseline, established lung injury (2 h), and end of protocol (6 h).
      Data were compared between groups at various stages of the model using one-way
      analysis of variance with repeated measures. RESULTS: All 10 animals survived the
      protocol. There was no difference between the experimental and control groups at
      baseline or established lung injury (2 h) for CI, SVI, PCWP, or VR. There was a
      significant improvement in PO2/FIO2 and reduction of PEEP values in the
      furosemide group. There was also a statistically significant difference between
      experimental and control groups in LIS, Qs/Qt, and urine volumes. CONCLUSIONS:
      Continuous dose furosemide therapy improves LIS, PO2/FIO2, and Qs/Qt and
      decreases PEEP requirements in this oleic acid model of ARDS.

PMID- 10068527
TI  - Thrombin induces production of growth factors from aortic smooth muscle cells.
AB  - BACKGROUND: Myointimal hyperplasia is a common complication of arterial
      recontructive surgery. The serine protease thrombin has a major role in vessel
      wall healing and eventual myointimal hyperplasia formation. The aim of this study
      was to determine the effect of thrombin on the production of PDGF AA and bFGF by
      arterial smooth muscle cells. MATERIALS AND METHODS: Bovine smooth muscle cells
      were stimulated with thrombin in a serum-free culture. The release of PDGF AA and
      bFGF was assessed by ELISA. The effect of thrombin on the proliferation of
      confluent monolayers of bovine smooth muscle cells was determined by tritiated
      thymidine uptake. RESULTS: Smooth muscle cells stimulated with thrombin released
      more PDGF AA (P < 0.001) and bFGF (P < 0.001) than the control. Addition of anti
      PDGF AA and anti-bFGF antibodies to the medium of smooth muscle cell cultures
      neutralized the mitogenic effect of thrombin (P < 0.001). CONCLUSIONS: The
      findings of our study suggest that thrombin may lead to myointimal hyperplasia
      formation through induction of PDGF and bFGF production by smooth muscle cells.

PMID- 10068528
TI  - Experimental study on the bilirubin metabolism after major hepatectomy:
      alterations in the proportions of bile bilirubin subfractions.
AB  - Bilirubin metabolism after major hepatectomy was investigated experimentally
      using rats. After a 70% and an 80% hepatectomy, proportions of bilirubin
      diglucuronide (BDG) decreased, and reversely, those of bilirubin monoglucuronide
      (BMG) increased. These changes were even more remarkable after an 80%
      hepatectomy. Parallel to the decrease in the proportions of BDG, the
      concentrations of uridine diphosphoglucuronic acid (UDP-GA) in the remnant liver
      decreased, and there was a significant correlation between the changes in BDG and
      UDP-GA. Although UDP-glucuronyltransferase (UDP-GT) activity and energy charge of
      the remnant liver also decreased after surgery, these decreases were mild and
      returned to the control level earlier than BDG. And there was no significant
      correlation between the changes in BDG and those in UDP-GT activity and energy
      charge. In this study, the decrease of the proportions of BDG in the bile juice
      was long term after partial hepatectomy and the period of the decrease became
      longer according to the augmentation of the volume of the hepatectomized liver.
      We clarified that the process of the UDP-GA production was inhibited after
      hepatectomy and the decrease of the proportions of BDG was derived from a
      deficiency of substrate of the glucuronidation, UDP-GA.

PMID- 10068529
TI  - A study of the effect of distension of the rectosigmoid junction on the rectum
      and anal canal with evidence of a rectosigmoid-rectal reflex.
AB  - PURPOSE: To elucidate the role of the rectosigmoid junction (RSJ) in the
      mechanism of defecation. METHOD: Fourteen healthy volunteers were enrolled in the
      study (10 men, 4 women; mean age 38.2 +/- 10.6 years). The pressures in the
      rectum, anal canal, and RSJ as well as rectal balloon expulsion were recorded in
      response to balloon distension of the RSJ in increments of 10 ml of carbon
      dioxide (CO2) to 50 ml. The experiments were repeated after individual
      anesthetization of the RSJ, rectum, and anal canal. The expulsion of a 50-ml
      distended balloon located in the anesthetized rectum was tested. RESULTS: RSJ
      distension with 10 ml of CO2 produced no significant pressure changes in the RSJ,
      rectum, or anal canal. A 20-ml distension effected a significant pressure rise in
      the RSJ (P < 0.05) and the rectum (P < 0.01) and a decline in the anal canal (P <
      0.05); the rectal balloon was expelled to the exterior. Similar pressure changes
      (P > 0.05) were recorded with a 30-, 40-, and 50-ml balloon distension. The mean
      latency for the RSJ response was 12.6 +/- 2.2 ms and for the rectum 15.8 +/- 2.6
      ms. The balloon, distended with 50 ml of CO2 and located in the rectum, was not
      expelled to the exterior. Balloon expulsion occurred only with distension with
      volumes of above 80 ml. Individual anesthetization of the RSJ, rectum, and anal
      canal followed by RSJ distension produced no significant pressure changes in RSJ,
      rectum, and anal canal as well as no rectal balloon expulsion. CONCLUSION: The
      rectal contraction upon RSJ distension affirms the hypothesis of the possible
      involvement of a reflex, which we term "rectosigmoid-rectal reflex." This reflex
      relationship is evidenced by reproducibility and its absence on anesthetization
      of either the RSJ or the rectum, both presumably representing the two arms of the
      reflex arc. It is postulated that stools passing from the sigmoid colon to the
      rectum distend the RSJ and evoke the rectosigmoid-rectal reflex, which produces
      rectal contraction. The role of the reflex in defecation disorders needs to be
      studied.

PMID- 10068530
TI  - Activated natural killer cell tumor retention and cytokine production in colon
      tumor using a tissue-isolated model.
AB  - BACKGROUND: Adoptively transferred activated natural killer (A-NK) cells are
      capable of selectively infiltrating solid tumors, but only at low efficiency when
      administered systemically. It is unclear if human A-NK cells can be retained in
      tumor tissue and, if so, what is their action. We investigated intratumor A-NK
      cell retention and in situ cytokine production, using an xenogeneic ex vivo
      tissue-isolated tumor model, which permits direct intraarterial infusion.
      MATERIALS AND METHODS: Human colon adenocarcinoma (HT-29) was implanted in the
      ovarian fat pad of nude rats. The tumors were perfused ex vivo 25 to 30 days
      postimplant with a known number of cells, and the effluent was collected over
      time. The number of human A-NK cells and cell surface antigen expression of cells
      infused and exiting the tumor were calculated, using cell counts and flow
      cytometry, respectively. Frozen sections were stained with Giemsa and also
      immunostained for the presence of interleukin-2, -4, and -10, tumor necrosis
      factor alpha (TNF-alpha), and interferon. RESULTS: Six perfusions with 8 x 10(6)
      A-NK cells were performed. The mean number of infused A-NK cells that remained in
      the tumor at the completion of perfusion was 4.74 x 10(6) (59.2%). No differences
      were noted in cellular phenotype between the infused cells and the cells exiting
      the tumor: expression of the markers CD45 (97.5% vs 94. 5%), CD14 (0 vs 0), CD3
      (3.83% vs 2.83%), and CD56 (86% vs 83%) was unchanged, P > 0.05. Microscopic
      examination of tumor sections showed tumor surrounded by A-NK cells, with some
      tumor nests infiltrated by A-NK cells. In situ immunopositivity for interleukin-2
      (2/6), interleukin-4 (3/6), interleukin-10 (2/6), and TNF-alpha (2/6) specimens
      was observed. Immunostaining for interferon-gamma was negative. Conclusions. The
      retention of A-NK cells in the transplanted human colon tumor tissue was found to
      be efficient (59.2 %) in this model. Although perfusion time was limited, A-NK
      cells were able to infiltrate the tumor and initiate cytokine production.

PMID- 10068531
TI  - Myocardial high-energy phosphates and hepatic redox state in jaundiced rats.
AB  - BACKGROUND: The mechanism underlying the fatal complications in jaundiced states
      after shock has not been fully clarified. The present study was designed to
      examine the effect of hemorrhagic shock on myocardial high-energy phosphate
      stores and the arterial ketone body ratio (AKBR:acetoacetate/beta
      hydroxybutyrate), which reflects the redox state of the liver mitochondria, in
      normal and jaundiced rats. MATERIALS AND METHODS: At 1 week after ligation of the
      common bile duct, hemorrhagic shock was induced by exsanguination (mean arterial
      blood pressure = 40 mmHg) and maintained for 2 h. Serial changes in AKBR were
      measured. The myocardial adenine nucleotides phosphocreatine (PCr) and inorganic
      phosphate (Pi) were determined before and after hemorrhagic shock. RESULTS:
      Before shock, myocardial ATP in the jaundiced group was lower than that in the
      sham group. However, the myocardial PCr levels in the two groups did not differ.
      After reinfusion of the shed blood, ATP and PCr recovered to the preshock levels
      in the sham group. However, ATP and PCr were further increased in the jaundiced
      group. At 60 min after reinfusion, AKBR recovered to the normal level in the sham
      group, but decreased below 0.7 in the jaundiced group. Metabolic acidosis was
      more severe in the jaundiced group than in the sham group. CONCLUSIONS: The
      decrease in AKBR indicated irreversible metabolic acidosis. As a result, fatal
      circulatory failure occurred, although the phosphoenergetic level in the
      myocardium was sufficiently maintained.

PMID- 10068532
TI  - Analysis of Pseudomonas aeruginosa clinical isolates for possible variations
      within the virulence genes exotoxin A and exoenzyme S.
AB  - We have previously characterized several Pseudomonas aeruginosa isolates that
      were obtained from patients with tracheal, urinary tract, or wound infections (A.
      H. Hamood, J. A. Griswold, and C. M. Duhan, 1996, J. Surg. Res. 61: 425).
      Analysis of additional isolates showed that regardless of the isolation site,
      some isolates produced significantly higher or significantly lower levels of
      either exotoxin A or exoenzyme S proteins. These variations did not correlate
      with the mucoid phenotype of the isolates. One aim of this study was to determine
      if the variations in the level of exotoxin A or exoenzyme S are due to DNA
      rearrangements within either the toxA or the exoS gene. This was accomplished by
      Southern blot hybridization experiments using a toxA internal probe, a toxA
      upstream probe, or an exoS internal probe. Hybridization with the toxA internal
      probe produced a 0.8-kb hybridizing fragment, whereas hybridization with the exoS
      internal probe produced either a 2.0- or a 2.3-kb hybridizing fragment.
      Hybridization with the toxA upstream probe, however, produced hybridizing
      fragments of varying sizes, regardless of their isolation site. Isolates that
      showed a similar hybridization fragment with either the toxA upstream probe or
      the exoS internal probe produced variable levels of exotoxin A or exoenzyme S.
      These results suggest that: [1] specific location within the host has no effect
      on either the mucoid phenotype of the isolate or the level of exotoxin A or
      exoenzyme S produced by the isolates; [2] although restriction polymorphism
      exists within the toxA upstream region, both the toxA and the exoS structural
      genes are relatively conserved; and [3] variations in the level of exoenzyme S
      and exotoxin A produced by different isolates do not correlate with either the
      observed heterogeneity within the toxA upstream region or the mucoid phenotype of
      the isolates.

PMID- 10068534
TI  - Advances in breast, endocrine, and cancer surgery 

PMID- 10068533
TI  - Glycyl-glutamine-enriched long-term total parenteral nutrition attenuates
      bacterial translocation following small bowel transplantation in the pig.
AB  - BACKGROUND: Improvements in immunosuppression, operative procedure, and
      posttransplant management have made clinical small bowel transplantation (SBT)
      feasible. Ischemia and reperfusion injury, total parenteral nutrition (TPN), and
      devoidment of enteral feeding lead to graft atrophy, gut barrier dysfunction, and
      bacterial translocation. Glutamine (Gln) is the principal fuel for the
      enterocyte. The influence of Gln dipeptide-supplemented TPN, especially long-term
      TPN, on intestinal graft permeability and bacterial translocation is not clear
      following SBT in the large animal model. Therefore, we studied the effect of
      glutamine dipeptide, glycyl-glutamine (Gly-Gln), on bacterial translocation
      following SBT in the pig, which has a physiology similar to humans. MATERIALS AND
      METHODS: The outbred pigs underwent segmental small bowel autotransplantation and
      were divided into two groups. In the STPN group (n = 5), the animal received
      standard TPN devoid of Gly-Gln for 28 days. In the GTPN group (n = 5), the animal
      received isonitrogenous (0.3 g/kg.day) and isocaloric (33 kcal/kg.day) TPN
      solution with 2% Gly-Gln for 28 days. RESULTS: At the end of the experiment, Gly
      Gln-enriched TPN could maintain the plasma Gln level, graft mucosal Gln and
      protein concentrations, and skeletal muscle Gln and protein concentrations. Gly
      Gln-enriched TPN significantly decreased the bacterial number of mesenteric lymph
      nodes in the liver and spleen and intestinal permeability to 99mTc-DTPA. There
      were no significant differences in body weight gain. CONCLUSIONS: The Gly-Gln
      enriched long-term TPN may maintain the plasma Gln level, mucosal and muscle Gln,
      and protein concentrations and attenuate the intestinal permeability to 99mTc
      DTPA and bacterial translocation following small bowel transplantation in the
      pig.

PMID- 10068569
TI  - Early immune activation in acute dengue illness is related to development of
      plasma leakage and disease severity.
AB  - T lymphocyte activation and increased cytokine levels have been described in
      retrospective studies of children presenting with dengue hemorrhagic fever (DHF).
      Serial plasma samples obtained in a prospective study of Thai children presenting
      with <72 h of fever were studied. Plasma levels of 80-kDa soluble tumor necrosis
      factor receptors (sTNFRs) were higher in children who developed DHF than in those
      with dengue fever (DF) or other nondengue febrile illnesses (OFIs) and were
      correlated with the degree of subsequent plasma leakage. Soluble CD8 and soluble
      interleukin-2 receptor levels were also elevated in children with DHF compared
      with those with DF. Interferon-gamma and sTNFR 60-kDa levels were higher in
      children with dengue than in those with OFIs. TNF-alpha was detectable more often
      in DHF than in DF or OFIs (P<.05). These results support the hypothesis that
      immune activation contributes to the pathogenesis of DHF. Further studies
      evaluating the predictive value of sTNFR80 for DHF are warranted.

PMID- 10068570
TI  - The molecular epidemiology and evolution of Epstein-Barr virus: sequence
      variation and genetic recombination in the latent membrane protein-1 gene.
AB  - The phylogeny and evolution of Epstein-Barr virus (EBV) genetic variation are
      poorly understood. EBV latent membrane protein-1 (LMP-1) gene sequences are
      especially heterogeneous and may be useful as a tool for EBV genotype
      identification. Therefore, LMP-1 sequences obtained directly from EBV-infected
      human tissues were examined by PCR amplification and cloning. EBV genotypes were
      defined as "strains" from among 22 identified LMP-1 sequence patterns. Three
      molecular mechanisms were identified by which genetic diversity arises in the LMP
      1 gene: point mutation, sequence deletion or duplication, and homologous
      recombination. The rate of LMP-1 gene evolution was found to be accelerated by
      coinfection with multiple EBV strains. The results of this study refine our
      understanding of LMP-1 sequence variation and enable accurate discrimination
      between independent EBV infection events and the consequence of intrahost EBV
      evolution. Thus, this LMP-1 sequence-based approach to EBV molecular epidemiology
      will facilitate the study of intrahost EBV infection, coinfection, and
      persistence.

PMID- 10068571
TI  - Core promoter mutations and genotypes in relation to viral replication and liver
      damage in East Asian hepatitis B virus carriers.
AB  - Virus load and liver damage, as measured by quantitative polymerase chain
      reaction and histology activity index, were related to genotype and core promoter
      mutations in 43 chronic hepatitis B virus (HBV) carriers of East Asian origin. T
      1762 mutants were more frequent in genotype C strains and were associated with
      more inflammation (P=.0036) and fibrosis (P=.0088) of the liver but not with
      hepatitis B e antigen (HBeAg) status or virus load. Conversely, precore mutations
      were associated with less liver inflammation (P=. 08), which was linked to HBeAg
      negativity and lower viral replication. Carriers with genotype C were more often
      HBeAg positive (P=.03) with precore wild type strains and more-severe liver
      inflammation (P=.009) than were those with genotype B. These findings suggest
      that pathogenic differences between genotypes may exist and that the T-1762
      mutation may be useful as a marker for progressive liver damage but seem to
      contradict that down-regulation of HBeAg production is the major effect of this
      mutation.

PMID- 10068572
TI  - Carriage of GB virus C/hepatitis G virus RNA is associated with a slower
      immunologic, virologic, and clinical progression of human immunodeficiency virus
      disease in coinfected persons.
AB  - The prevalence of GB virus C (GBV-C) infection is high in human immunodeficiency
      virus (HIV)-infected persons. However, the long-term consequences of coinfection
      are unknown. HIV-positive persons with a well-defined duration of infection were
      screened on the basis of their GBV-C/hepatitis G virus (HGV) RNA status and
      studied. GBV-C/HGV viremia was observed in 23, who carried the virus over a mean
      of 7.7 years. All parameters (survival, CDC stage B/C, HIV RNA load, CD4 T cell
      count) showed significant differences in terms of the cumulative progression rate
      between persons positive and negative for GBV-C/HGV RNA. When GBV-C/HGV RNA
      positive and -unexposed subjects were matched by age, sex, baseline HIV RNA load,
      and baseline CD4 T cell count, HIV disease progression appeared worse in GBV
      C/HGV RNA-negative subjects. The carriage of GBV-C/HGV RNA is associated with a
      slower progression of HIV disease in coinfected persons.

PMID- 10068573
TI  - Outcome and predictors of failure of highly active antiretroviral therapy: one
      year follow-up of a cohort of human immunodeficiency virus type 1-infected
      persons.
AB  - The outcome and predictors of virologic treatment failure of highly active
      antiretroviral therapy (HAART) were determined for 271 human immunodeficiency
      virus (HIV)-infected protease inhibitor-naive persons. During a follow-up of 48
      weeks after the initiation of HAART, 6.3% of patients experienced at least one
      new AIDS-defining event, and 3.0% died. Virologic treatment failure occurred in
      40% (indinavir, 27%; ritonavir, 30%; saquinavir, 59%; ritonavir plus saquinavir,
      32%; chi2, P=.001). Risk factors for treatment failure were baseline plasma HIV-1
      RNA (odds ratio [OR], 1.70 per log10 copies increase in plasma HIV-1 RNA),
      baseline CD4 cell count (OR, 1. 35 per 100 CD4 cells/mm3 decrease), and use of
      saquinavir versus other protease inhibitors (OR, 3.21). During the first year of
      treatment, 53% of all patients changed (part of) their original HAART regimen at
      least once. This was significantly more frequent for regimens containing
      saquinavir (62%; 27% for virologic failure) or ritonavir (64%; 55% for
      intolerance) as single protease inhibitor.

PMID- 10068574
TI  - Characterization of viral dynamics in human immunodeficiency virus type 1
      infected patients treated with combination antiretroviral therapy: relationships
      to host factors, cellular restoration, and virologic end points.
AB  - Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir,
      zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1
      as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were
      significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and
      CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline
      virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery
      (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T
      lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG
      that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral
      decay rates were not predictive of treatment failure or durability of viral
      suppression. These exploratory findings are consistent with a model in which
      immunologic factors contribute to elimination of HIV-infected cells and suggest a
      dynamic interplay between regulation of HIV expression and lymphocyte activation
      and recovery.

PMID- 10068575
TI  - Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in
      adults with human immunodeficiency virus infection. AIDS Clinical Trials Group
      347 Study Team.
AB  - Amprenavir is a human immunodeficiency virus (HIV) protease inhibitor with a
      favorable pharmacokinetic profile and good in vitro activity. Ninety-two
      lamivudine- and protease inhibitor-naive individuals with >/=50 CD4 cells/mm3 and
      >/=5000 HIV RNA copies/mL were assigned amprenavir (1200 mg) alone or with
      zidovudine (300 mg) plus lamivudine (150 mg), all given every 12 h. After a
      median follow-up of 88 days, the findings of a planned interim review resulted in
      termination of the amprenavir monotherapy arm. Among 85 subjects with confirmed
      plasma HIV RNA determination, 15 of 42 monotherapy versus 1 of 43 triple-therapy
      subjects had an HIV RNA increase above baseline or 1 log10 above nadir (P=.0001).
      For subjects taking triple therapy at 24 weeks, the median decrease in HIV RNA
      was 2.04 log10 copies/mL, and 17 (63%) of 27 evaluable subjects had <500 HIV RNA
      copies/mL. Treatment with amprenavir, zidovudine, and lamivudine together reduced
      the levels of HIV RNA significantly more than did amprenavir monotherapy.

PMID- 10068576
TI  - Proliferative responses to human immunodeficiency virus type 1 (HIV-1) gp120
      peptides in HIV-1-infected individuals immunized with HIV-1 rgp120 or rgp160
      compared with nonimmunized and uninfected controls.
AB  - The proliferative responses to a series of peptides constituting the human
      immunodeficiency virus type 1 (HIV-1) gp120 sequence were evaluated in 19 HIV-1
      infected rgp160 vaccine recipients, 17 HIV-1-infected rgp120 vaccine recipients,
      15 HIV-1-infected placebo recipients, and 18 HIV-1-uninfected controls. Many
      regions of the gp120 molecule were found to contribute proliferative epitopes,
      although there were clearly regions of relative dominance and silence. Vaccine
      recipients tended to have broader, more robust, and more frequent peptide
      recognition than the placebo recipients. Despite the considerable variability in
      the pattern of peptide recognition among individuals, there was a striking
      similarity between the rgp160 and rgp120 vaccinee groups as a whole. Low-risk HIV
      1-uninfected individuals may react to a few peptides within the gp120 sequence as
      well, despite a lack of significant response to the whole gp120 protein.

PMID- 10068577
TI  - No evidence for an effect of the CCR5 delta32/+ and CCR2b 64I/+ mutations on
      human immunodeficiency virus (HIV)-1 disease progression among HIV-1-infected
      injecting drug users.
AB  - The relationship between CCR5 and CCR2b genotypes and human immunodeficiency
      virus (HIV)-1 disease progression was studied among the 108 seroconverters of the
      Amsterdam cohort of injecting drug users (IDUs). In contrast to earlier studies
      among homosexual men, no effect on disease progression of the CCR5 Delta32/+ and
      the CCR2b 64I/+ genotypes was found, when progression to AIDS, death, or a CD4
      cell count <200/microL was compared by a Cox proportional hazards model.
      Furthermore, CD4 cell decline (by a regression model for repeated measurements)
      and virus load in the first 3 years after seroconversion did not differ between
      the CCR5 and CCR2b wild type and heterozygous genotypes. A nested matched case
      control study also revealed no significant effect of the CCR5 and CCR2b
      mutations. Immunologic differences between IDUs and homosexual men may account
      for the observed lack of effect. Alternatively, difference in transmission route
      or characteristics of the HIV-1 variants that circulate in IDUs could also
      explain this phenomenon.

PMID- 10068578
TI  - Enhanced production of tumor necrosis factor-alpha and interleukin-6 due to
      prolonged response to lipopolysaccharide in human macrophages infected in vitro
      with human immunodeficiency virus type 1.
AB  - Elevated levels of circulating tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6 have been detected in human immunodeficiency virus (HIV) type 1 infection.
      The overproduction of these cytokines could contribute to AIDS pathogenesis.
      Thus, the expression of TNF-alpha and IL-6 in human macrophages infected with HIV
      1 was investigated. HIV-1 infection, per se, did not induce any TNF-alpha or IL-6
      production or cytokine-specific mRNA expression. In contrast, HIV-1 primed
      macrophages to a prolonged TNF-alpha and IL-6 response to lipopolysaccharide
      (LPS) stimulation with respect to uninfected cells. Time-course analysis and flow
      cytometry demonstrated that cytokine production stopped at 6 h in uninfected
      macrophages but continued up to 24 h in HIV-1-infected cells. RNA studies
      suggested that HIV-1 interfered with late steps of cytokine synthesis. No
      modulation of membrane CD14 was found to account for the enhanced response to
      LPS. Finally, the effect of HIV-1 on cytokine response could not be abolished by
      the antiviral compound U75875.

PMID- 10068579
TI  - Stability of plasma levels of cytokines and soluble activation markers in
      patients with human immunodeficiency virus infection.
AB  - Cytokine and immune activation marker levels in plasma are valuable measurements
      of immune status and treatment effects in human immunodeficiency virus (HIV)
      infection and AIDS. Five populations representing various stages of disease were
      studied: controls, 2 AIDS groups with <50/mm3 CD4 cells, and 2 groups of HIV
      positive subjects-1 with stable CD4 T cells (median, 545/mm3) and 1 with >100/mm3
      CD4 cell decline in 1 year. Relatively stable levels of tumor necrosis factor
      (TNF)-alpha, soluble TNF receptor (R)II, soluble interleukin-2R, neopterin, and
      beta2-microglobulin (beta2M) were documented over 5-8 weeks in patients with AIDS
      and for 1-4 years in the other groups. beta2M was generally the most stable
      marker. Interferon-gamma levels, however, fluctuated substantially. Individuals,
      whether normal or HIV-positive, maintain characteristic plasma levels of
      cytokines and immune activation markers. Thus, documented changes, in excess of
      the variability observed in this study, are likely to be significant indicators
      of change in disease status or effects of therapy.

PMID- 10068580
TI  - A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient
      therapy for early human immunodeficiency virus type 1 infection.
AB  - Forty-nine outpatients infected with human immunodeficiency virus with baseline
      CD4 cell counts >/=500/mm3, who were on stable antiretroviral therapy, were
      randomized to receive 5-day cycles of either low-dose (1.5 million IU [MIU] twice
      a day) or high-dose (7.5 MIU twice a day) subcutaneous (sc) interleukin (IL)-2
      every 4 or every 8 weeks. High-dose recipients experienced mean slopes of +116.1
      cells/month and +2.7 %/month in CD4 cells and percents, respectively, whereas low
      dose recipients displayed mean slopes of +26.7 and +1.3% in the same parameters.
      At month 6, high-dose recipients achieved a 94.8% increase in mean CD4 cells over
      baseline compared with a 19.0% increase in low-dose recipients. While high-dose
      recipients encountered more constitutional side effects, these were generally not
      dose-limiting. High-dose scIL-2 therapy in outpatients with early HIV-1 infection
      was well tolerated and induced dramatic, sustained rises in CD4 cells.

PMID- 10068581
TI  - Shorter survival in advanced human immunodeficiency virus type 1 infection is
      more closely associated with T lymphocyte activation than with plasma virus
      burden or virus chemokine coreceptor usage.
AB  - To define predictors of survival time in late human immunodeficiency virus type 1
      (HIV-1) disease, long- and short-duration survivors were studied after their CD4+
      T cells fell to </=50/mm3. Immune activation of CD4+ and CD8+ T cells, as
      measured by elevated cell surface expression of CD38 antigen, was strongly
      associated with shorter subsequent survival (P</=.002). The naive CD45RA+CD62L+ T
      cell reserve was low in all subjects and did not predict survival (P=.34 for CD4+
      and.08 for CD8+ cells). Higher virus burden correlated with CD8+ but not CD4+
      cell activation and, after correcting for multiple comparisons, was not
      associated with shorter survival (P=.02). All of the patients' viruses used CCR5,
      CXCR4, or both, and coreceptor usage did not predict survival (P=. 27). Through
      mechanisms apparently unrelated to higher virus burden, immune activation is a
      major determinant of survival in advanced HIV-1 disease.

PMID- 10068582
TI  - Correlation of human immunodeficiency virus type 1 RNA levels in blood and the
      female genital tract.
AB  - In this study, the correlations of human immunodeficiency virus type 1 (HIV-1)
      RNA levels in blood plasma, vaginal secretions, and cervical mucus of 52 HIV-1
      infected women were determined. The amount of cell-free HIV-1 RNA in blood plasma
      was correlated with that in vaginal secretions (Spearman's rank correlation
      coefficient (r) = 0.64, P<.001). In both blood plasma and vaginal secretions, the
      amounts of cell-free and cell-associated HIV-1 RNA were highly correlated
      (r=0.76, P<.01 and r=0.85, P<.01, respectively). Cell-free HIV-1 RNA levels in
      blood plasma and vaginal secretions were negatively correlated with CD4+ T
      lymphocyte count (r=-0.44, P<.01 and r=-0.40, P<.01, respectively). Similar to
      the effect observed in blood plasma, initiation of antiretroviral therapy
      significantly reduced the amount of HIV-1 RNA in vaginal secretions. These
      findings suggest that factors that lower blood plasma virus load may also reduce
      the risk of perinatal and female-to-male heterosexual transmission by lowering
      vaginal virus load.

PMID- 10068583
TI  - Transmission dynamics of epidemic methicillin-resistant Staphylococcus aureus and
      vancomycin-resistant enterococci in England and Wales.
AB  - A simple epidemiological framework for the analysis of the transmission dynamics
      of hospital outbreaks of epidemic methicillin-resistant Staphylococcus aureus
      (EMRSA) and vancomycin-resistant enterococci (VRE) in hospitals in England and
      Wales is presented. Epidemic strains EMRSA-15 and EMRSA-16 are becoming endemic
      in hospitals in the United Kingdom, and theory predicts that EMRSA-15 and EMRSA
      16 will reach respective endemic levels of 158 (95% confidence interval [CI], 143
      173) and 116 (95% CI, 109-123) affected hospitals with stochastic fluctuations of
      up to 30 hospitals in each case. An epidemic of VRE is still at an early stage,
      and the incidence of hospitals newly affected by VRE is growing exponentially at
      a rate r=0.51/year (95% CI, 0.48-0.54). The likely impact of introducing
      surveillance policies if action is taken sufficiently early is estimated.
      Finally, the role of heterogeneity in hospital size is considered: "Super
      spreader hospitals" may increase transmission by 40%-132% above the expected
      mean.

PMID- 10068584
TI  - Molecular analysis of the genetic variation among penicillin-susceptible and
      penicillin-resistant Streptococcus pneumoniae serotypes in Canada.
AB  - Few studies have examined the genetic relatedness within and between serotypes of
      Streptococcus pneumoniae. Penicillin-susceptible S. pneumoniae (PSSP) isolates
      (n=170) and penicillin-resistant S. pneumoniae (PRSP) isolates (n=48) belonging
      to 13 different serotypes from across Canada were studied to further understand
      the molecular epidemiology of S. pneumoniae. PRSP of serotypes 6B, 14, and 19F
      appeared to be novel clones, differentiated by pulsed-field gel electrophoresis
      from the recognized international penicillin-resistant clones belonging to these
      serotypes. In addition, not all PRSP strains shared similar genetic backgrounds
      with PSSP strains of the same serotype, suggesting that in Canada, certain PRSP
      strains have emerged from new unique lineages of PRSP. Although there was
      significant heterogeneity among S. pneumoniae of different serotypes, certain
      serotypes (3, 7F, and 22F) appeared to be more clonally related despite having
      originated from different geographic regions.

PMID- 10068585
TI  - Protective immune response against Streptococcus pyogenes in mice after
      intranasal vaccination with the fibronectin-binding protein SfbI.
AB  - Despite the significant impact on human health of Streptococcus pyogenes, an
      efficacious vaccine has not yet been developed. Here, the potential as a vaccine
      candidate of a major streptococcal adhesin, the fibronectin-binding protein SfbI,
      was evaluated. Intranasal immunization of mice with either SfbI alone or coupled
      to cholera toxin B subunit (CTB) triggered efficient SfbI-specific humoral
      (mainly IgG) and lung mucosal (14% of total IgA) responses. CTB-immunized control
      mice were not protected against challenge with S. pyogenes (90%-100% lethality),
      whereas SfbI-vaccinated animals showed 80% and 90% protection against homologous
      and heterologous challenge, respectively. Multiple areas of consolidation with
      diffused cellular infiltrates (macrophages and neutrophils) were observed in
      lungs from control mice; the histologic structure was preserved in SfbI
      vaccinated animals, which occasionally presented focal infiltrates confined to
      the perivascular, peribronchial, and subpleural areas. These results suggest that
      SfbI is a promising candidate for inclusion in acellular vaccines against S.
      pyogenes.

PMID- 10068586
TI  - Interaction between group A streptococci and the plasmin(ogen) system promotes
      virulence in a mouse skin infection model.
AB  - Group A streptococci are capable of acquiring a surface-associated, unregulatable
      plasmin-like enzymatic activity when incubated in human plasma. The effect of
      this enzymatic activity on virulence of group A isolate CS101 was examined in a
      mouse skin infection model. Initial studies demonstrated enhanced virulence for
      bacteria preincubated in human plasma but not in plasminogen-depleted plasma. A
      direct correlation between surface-associated enzymatic activity and virulence
      was not observed; however, an association between virulence and the assembly of a
      surface-associated plasminogen activator that could activate mouse plasminogen
      was noted. This activity enhanced virulence in wild type but not in plg-/-
      plasminogen-deficient mice. These results support the hypothesis that acquisition
      of a surface-associated plasmin(ogen)-dependent enzymatic activity can contribute
      to the virulence of group A streptococcal invasive infections.

PMID- 10068587
TI  - Temporal trends in the population structure of Bordetella pertussis during 1949
      1996 in a highly vaccinated population.
AB  - The population structure of Bordetella pertussis in The Netherlands in 5
      successive periods, encompassing 1949-1996, was analyzed by DNA typing
      ("fingerprinting"). In 10 years following the introduction of wide-scale
      vaccination in 1953, a decrease in genotypic diversity (GD) was observed,
      suggesting clonal expansion of strains that were adapted to vaccine-induced
      immunity. In subsequent periods, GD increased to prevaccination levels, probably
      reflecting a gradual adaptation of the B. pertussis population involving many
      lineages. In the 1990s, GD decreased again. This decrease coincided with an
      antigenic shift in the surface protein pertactin. No evidence was found for
      changes in DNA types or GD in 1996, when a large pertussis epidemic occurred.
      Thus, gradual changes in the bacterial population previous to 1996 were probably
      the cause of the 1996 epidemic. The results herein suggest that vaccination has
      selected for strains that are adapted to a highly vaccinated population. Similar
      changes may have occurred in other countries, explaining the reemergence of
      pertussis in vaccinated populations.

PMID- 10068588
TI  - Activation of human immunodeficiency virus type 1 expression by Gardnerella
      vaginalis.
AB  - Bacterial vaginosis (BV) is associated with an increased rate of sexual
      transmission of human immunodeficiency virus (HIV) type 1, and Gardnerella
      vaginalis is frequently isolated from the genital tracts of women with BV. G.
      vaginalis lysates were found to significantly stimulate HIV expression in
      monocytoid cells. Stimulation was significantly higher when lysates were heated
      at 100 degrees C for 5 min but was reduced by treatment with lysozyme or
      protease. G. vaginalis lysates also activated HIV expression in certain T cell
      lines. G. vaginalis lysates activated HIV long-terminal repeat transcription in
      HIV-infected cells and increased NF-kappaB binding activity, indicating an effect
      by G. vaginalis on HIV transcription. The activation of HIV production by G.
      vaginalis suggests that genital tract infection with G. vaginalis increases the
      risk of HIV transmission by increasing HIV expression in the genital tract. This
      may explain, at least in part, the increased rate of HIV transmission in women
      with BV.

PMID- 10068589
TI  - Evaluation of two-test serodiagnostic method for early Lyme disease in clinical
      practice.
AB  - The Centers for Disease Control and Prevention (CDC) recommend a two-test
      approach for the serodiagnosis of Lyme disease (LD), with EIA testing followed by
      Western immunoblotting (WB) of EIA-equivocal and -positive specimens. This
      approach was compared with a simplified two-test approach (WB of EIA equivocals
      only) and WB alone for early LD. Case-patients with erythema migrans (EM) rash
      >/=5 cm were recruited from three primary-care practices in LD-endemic areas to
      provide acute- (S1) and convalescent-phase serum specimens (S2). The simplified
      approach had the highest sensitivity when either S1 or S2 samples were tested,
      nearly doubling when S2 were tested, while decreasing slightly for the other two
      approaches. Accordingly, the simplified approach had the lowest negative
      likelihood ratio for either S1 or S2. For early LD with EM, the simplified
      approach performed well and was less costly than the other testing approaches
      since less WB is required.

PMID- 10068590
TI  - Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen
      activated protein kinase pathways block inducible nitric oxide synthase and tumor
      necrosis factor accumulation in murine macrophages stimulated with
      lipopolysaccharide and interferon-gamma.
AB  - Whether p38 and extracellular signal-regulated kinase (ERK) mitogen-activated
      protein kinase cascades are required for inducible nitric oxide synthase (iNOS)
      and tumor necrosis factor (TNF) accumulation in RAW 264.7 murine macrophages
      exposed to lipopolysaccharide (LPS) plus recombinant interferon-gamma (rIFN
      gamma) was investigated. By use of Western blotting for iNOS detection and ELISA
      for quantitation of TNF secretion, three selective inhibitors of these pathways
      were tested (the p38 inhibitors SB202190 and SB203580 and the MEK 1,2/ERK
      inhibitor PD98059). Dose-related inhibition of iNOS production was demonstrated
      when inhibitors were added 1 h before, simultaneously with, or 1 h after LPS plus
      rIFN-gamma stimulation. In contrast, inhibition of TNF secretion was observed
      only when cells were preincubated with these agents. Thus, both the p38 and ERK
      pathways are involved in the up-regulation of iNOS and TNF production by murine
      macrophages, and specific inhibitors of these pathways block macrophage iNOS
      production even when added 1 h after activation of these cells.

PMID- 10068591
TI  - Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis.
AB  - Mycobacterium tuberculosis (MTB)-induced T cell responses are depressed in
      peripheral blood mononuclear cells of persons with newly diagnosed pulmonary
      tuberculosis (TB), and levels of interferon (IFN)-gamma remain low even after
      completion of antituberculous therapy. Loss of MTB-reactive T cells through
      apoptotic mechanisms could account for this prolonged T cell hyporesponsiveness.
      T cell apoptosis was studied in TB patients and healthy control subjects. Both
      spontaneous and MTB-induced apoptosis (in CD4 and non-CD4 T cells) from TB
      patients was increased when compared with healthy control subjects, whereas
      coculture with control antigen (candida) had no effect on T cell apoptosis in
      either group of study subjects. An inverse correlation existed between increased
      MTB-induced T cell apoptosis and IFN-gamma and interleukin (IL)-2
      immunoreactivities. Successful antituberculous chemotherapy resulted in a 50%
      reduction in both spontaneous and MTB-induced apoptosis, which coincided with 3-
      and 8-fold increases in levels of MTB-stimulated IL-2 and IFN-gamma,
      respectively. These data indicate that apoptotic pathways are operant during
      active MTB infection and may contribute to deletion of MTB-reactive T cells and
      the immunopathogenesis of this disease.

PMID- 10068592
TI  - Persistent chlamydial envelope antigens in antibiotic-exposed infected cells
      trigger neutrophil chemotaxis.
AB  - An in vitro coculture model system was used to explore conditions that trigger
      neutrophil chemotaxis to Chlamydia trachomatis infected human epithelial cells
      (HEC-1B). Polarized HEC-1B monolayers growing on extracellular matrix (ECM) were
      infected with C. trachomatis serovar E. By 36 h, coincident with the secretion of
      chlamydial lipopolysaccharide and major outer membrane protein to the surfaces of
      infected cells, human polymorphonuclear neutrophils (PMNL) loaded with
      azithromycin migrated through the ECM and infiltrated the HEC-1B monolayer.
      Bioreactive azithromycin was delivered by the chemotactic PMNL to infected
      epithelial cells in concentrations sufficient to kill intracellular chlamydiae.
      However, residual chlamydial envelopes persisted for 4 weeks, and PMNL chemotaxis
      was triggered to epithelial cells containing residual envelopes. Infected
      endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA.
      Thus, despite appropriate antimicrobial therapy, residual chlamydial envelope
      antigens may persist in infected tissues of culture-negative women and provide
      one source for sustained inflammation.

PMID- 10068593
TI  - Cytokine profile induced by Cryptosporidium antigen in peripheral blood
      mononuclear cells from immunocompetent and immunosuppressed persons with
      cryptosporidiosis.
AB  - The proliferative response of peripheral blood mononuclear cells (PBMC) to a
      crude extract from Cryptosporidium parvum (CCE) was studied in persons who
      acquired cryptosporidiosis in the same outbreak (15 immunocompetent subjects with
      prior cryptosporidiosis and 22 human immunodeficiency virus [HIV]-positive
      persons with various levels of immunosuppression and active cryptosporidiosis)
      and in individual patients (8 HIV-positive patients with active cryptosporidiosis
      and 15 HIV-positive persons without history of cryptosporidiosis). PBMC from HIV
      positive persons showed less proliferation to CCE and mitogens than did PBMC from
      immunocompetent subjects with prior cryptosporidiosis, independent of CD4 cell
      count. In immunocompetent subjects, cytokine gene expression was consistent with
      cytokine production, whereas in HIV-positive subjects it was not. The production
      of interferon-gamma in CCE-stimulated PBMC from both immunocompetent and HIV
      positive subjects with cryptosporidiosis and the lack of interferon-gamma in CCE
      stimulated PBMC from HIV-positive subjects without cryptosporidiosis indicate
      that C. parvum mainly induces a Th1 response.

PMID- 10068594
TI  - Intrinsic efficacy of proguanil against falciparum and vivax malaria independent
      of the metabolite cycloguanil.
AB  - Mutations in human CYP2C19 and parasite dihydrofolate reductase (dhfr) genes,
      related to poor metabolism of proguanil and resistance to cycloguanil,
      respectively, have both been assumed to be associated with poor antimalarial
      effect by proguanil. To study this, 95 subjects with uncomplicated Plasmodium
      falciparum or Plasmodium vivax infections in Vanuatu received proguanil treatment
      for 3 days (adult relative dose of 300-500 mg/day) and were followed up for 28
      days. A similarly high antimalarial efficacy against both infections was observed
      in 62 patients with CYP2C19-related poor metabolizer genotype and in 33 with
      extensive metabolizer genotype, even though blood cycloguanil was significantly
      more often detected in those with extensive metabolizer genotype than in those
      with poor metabolizer genotype. All 28 P. falciparum isolates had two dhfr
      mutations (residues 59 and 108), suggesting moderate resistance to cycloguanil.
      The results suggest that the parent compound proguanil has significant intrinsic
      efficacy against falciparum and vivax malaria independent of the metabolite
      cycloguanil.

PMID- 10068595
TI  - Interferon-gamma responses are associated with resistance to reinfection with
      Plasmodium falciparum in young African children.
AB  - The contribution of T cell-mediated responses was studied with regard to
      resistance to reinfection in groups of Gabonese children participating in a
      prospective study of severe and mild malaria due to infection with Plasmodium
      falciparum. In those admitted with mild malaria, but not in those with severe
      malaria, production of IFN-gamma by peripheral blood mononuclear cells (PBMC) in
      response to either liver-stage or merozoite antigen peptides was associated with
      significantly delayed first reinfections and with significantly lower rates of
      reinfection. Proliferative or tumor necrosis factor responses to the same
      peptides showed no such associations. Production of interferon-gamma by PBMC in
      response to sporozoite and merozoite antigen peptides was observed in a higher
      proportion of those presenting with mild malaria. Differences in the Th1/Th2
      cytokine balance may be linked to the ability to control parasite multiplication
      in these young children, helping to explain the marked differences observed in
      both susceptibility to infection as well as in clinical presentation.

PMID- 10068596
TI  - Complexity of Plasmodium falciparum infections is consistent over time and
      protects against clinical disease in Tanzanian children.
AB  - The complexity of Plasmodium falciparum populations in 21 children was studied in
      repetitive samples over 4 years in an area of Tanzania where the organism is
      holoendemic. Genotyping was done by a polymerase chain reaction method that
      targets three highly polymorphic regions of the merozoite surface protein (MSP) 1
      block 2, MSP 2, and the glutamine-rich protein. Eight children were repeatedly
      parasitemic, 5 had scanty parasitemias, and 8 were consistently nonparasitemic.
      Varying numbers of genotypes were detected in the parasitemic children, but the
      multiplicity of infection was significantly constant within each child. The
      children with frequent parasitemias experienced fewer clinical episodes during
      the study period than those without parasitemias. There was also a tendency for
      children with more complex infections to experience fewer episodes. The children
      had consistent parasitologic profiles over the 4 years. Although few subjects
      were studied and the results will require confirmation, the results suggest that
      asymptomatic (especially polyclonal) P. falciparum infection protects against
      clinical disease from new infections.

PMID- 10068597
TI  - Double-blind placebo-controlled study of concurrent administration of albendazole
      and praziquantel in schoolchildren with schistosomiasis and geohelminths.
AB  - A double-blind placebo-controlled study of the concurrent administration of
      albendazole and praziquantel was conducted in>1500 children with high prevalences
      of geohelminths and schistosomiasis. The study sites were in China and the
      Philippines, including 2 strains of Schistosoma japonicum, and 2 different
      regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma
      haematobium. Neither medication affected the cure rate of the other. There was no
      difference between the side effect rate from albendazole or the double placebo.
      Praziquantel-treated children had more nausea, abdominal pain, and headache but
      these side effects were statistically more common in children with
      schistosomiasis, suggesting a strong influence of dying parasites. The subjects
      were followed for 6 months for changes in infection status, growth parameters,
      hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month
      increase in serum hemoglobin was observed in children who received praziquantel,
      strongly supporting population-based mass treatment.

PMID- 10068598
TI  - Class II HLA alleles and hepatitis B virus persistence in African Americans.
AB  - Persistence of hepatitis B virus (HBV) infection is likely due to the interplay
      of the virus and host immune response. Given its critical role in antigen
      presentation, allelic differences in the HLA complex may affect HBV persistence.
      In a prospectively followed African American cohort, molecular class I and class
      II HLA typing was done on 31 subjects with persistent HBV infection and 60
      controls who cleared the infection. HBV persistence was significantly associated
      with two class II alleles, DQA1 *0501 (odds ratio [OR], 2.6; P=.05) and DQB1
      *0301 (OR, 3.9; P=.01), the two-locus haplotype consisting of these same two
      alleles (OR, 3; P=. 005) and the three-locus haplotype, DQA1 *0501, DQB1 *0301,
      and DRB1 *1102 (OR, 10.7; P=.01). In addition, HBV persistence was associated
      with class II allelic homozygosity. Several class I associations with persistence
      were also noted but were not statistically significant after correction for
      multiple comparisons. These results underscore the importance of the class II
      mediated immune response in recovery from HBV infection.

PMID- 10068599
TI  - Experimental transmission of hepatitis C virus-associated fulminant hepatitis to
      a chimpanzee.
AB  - Hepatitis C virus (HCV) was transmitted from a patient with fulminant hepatitis C
      to a chimpanzee. The patient had developed two episodes of fulminant hepatitis C,
      each occurring after a separate liver transplantation. Serial serum and liver
      samples from the patient and the chimpanzee were analyzed for HCV replication,
      genotype, quasispecies heterogeneity, and antibodies. In the patient, the levels
      of HCV replication in serum and liver correlated with the degree of
      hepatocellular necrosis and the clinical expression of fulminant hepatitis. The
      same HCV strain, genotype 1a, was recovered from both episodes of fulminant
      hepatitis. An unusually severe acute hepatitis was also observed in the
      chimpanzee. The viruses recovered from the patient and the chimpanzee were almost
      identical and displayed relatively little quasispecies heterogeneity. Thus, the
      same HCV strain induced two episodes of fulminant hepatitis in a single patient
      and severe hepatitis in a chimpanzee, suggesting that the pathogenicity or
      virulence of a specific HCV strain may be important in the pathogenesis of
      fulminant hepatitis C.

PMID- 10068600
TI  - Persistently high Epstein-Barr virus (EBV) loads in peripheral blood lymphocytes
      from patients with chronic active EBV infection.
AB  - Chronic active Epstein-Barr virus infection (CAEBV) is a severe illness with
      unusual EBV activation that persists for years, and its pathogenesis is largely
      unknown. After the creation of an accurate and reproducible polymerase chain
      reaction system to quantify EBV DNA, virus loads in peripheral blood lymphocytes
      (PBL) were determined in 54 children: 15 with CAEBV, 16 with infectious
      mononucleosis (IM), and 23 healthy children. Children with CAEBV and those with
      IM had high virus loads. Lower loads were detected in 47% of seropositive healthy
      donors. There were two distinct differences between children with CAEBV and those
      with IM: The former had greater viral replication (10(3)-10(7) copies/2.5x10(5)
      PBL) than those with IM, and viral replication declined in children with IM
      whereas active replication persisted for years in subjects with CAEBV. Persisting
      high virus loads are a possible diagnostic criterion for CAEBV. EBV loads may
      enable classification and prognosis of EBV infections.

PMID- 10068601
TI  - Human serum antibodies to a major defined epitope of human herpesvirus 8 small
      viral capsid antigen.
AB  - The major antibody-reactive epitope of the small viral capsid antigen (sVCA) of
      human herpesvirus 8 (HHV-8) was defined by use of overlapping peptides. Strong
      IgG reactivity was found among approximately 50% of 44 human immunodeficiency
      virus-positive or -negative patients with Kaposi's sarcoma and 13 subjects who
      were seropositive by immunofluorescence assay (IFA) for the latent HHV-8 nuclear
      antigen. Only 1 of 106 subjects seronegative for both lytic and latent HHV-8
      antigens and 10 of 81 subjects IFA-seropositive only for the lytic HHV-8 antigen
      had strong IgG reactivity to this epitope. Among 534 healthy Swedish women, only
      1.3% were strongly seropositive. Comparison of the peptide-based and purified
      sVCA protein-based ELISAs found 55% sensitivity and 98% specificity. However,
      only 1 of 452 serum samples from healthy women was positive in both tests. In
      conclusion, the defined sVCA epitope was a specific, but not very sensitive,
      serologic marker of active HHV-8 infection. Such infection appears to be rare
      among Swedish women, even with sexual risk-taking behavior.

PMID- 10068602
TI  - A reanalysis of IgM Western blot criteria for the diagnosis of early Lyme
      disease.
AB  - A two-step approach for diagnosis of Lyme disease, consisting of an initial EIA
      followed by a confirmatory Western immunoblot, has been advised by the Centers
      for Disease Control and Prevention (CDC). However, these criteria do not examine
      the influence of the prior probability of Lyme disease in a given patient on the
      predictive value of the tests. By using Bayesian analysis, a mathematical
      algorithm is proposed that computes the probability that a given patient's
      Western blot result represents Lyme disease. Assuming prior probabilities of
      early Lyme disease of 1%-10%, the current CDC minimum criteria for IgM immunoblot
      interpretation yield posttest probabilities of 4%-32%. The value of the two-step
      approach for diagnosis of early Lyme disease may be limited in populations at
      lower risk of disease or when patients present with atypical signs and symptoms.

PMID- 10068603
TI  - Application of molecular methods for detection and transmission analysis of
      mycobacterium tuberculosis drug resistance in patients attending a reference
      hospital in Italy.
AB  - A molecular analysis of drug-resistant isolates of Mycobacterium tuberculosis was
      done in a population with a high prevalence of human immunodeficiency virus
      infection. Seventy-one consecutive isolates were tested for genotypic resistance
      to isoniazid, rifampicin, streptomycin, and ethambutol by polymerase chain
      reaction-single strand conformation polymorphism analysis and automated
      sequencing of target regions. Phenotypic and genotypic resistance to isoniazid,
      rifampicin, streptomycin, and ethambutol were detected in 23.4%, 11.2%, 7%, and
      5.6% of isolates and in 87%, 88%, 40%, and 100% of resistant isolates,
      respectively. Specificity was 100% for all target regions. When rpoB, katG, and
      ahpC mutation analysis were combined, 86% of resistant isolates to any drug were
      identified. No mutations in inhA were found in isoniazid-resistant isolates.
      Molecular detection of drug resistance, particularly for isoniazid and
      rifampicin, may represent a sensitive and very specific technique. The strategy
      of selecting rpoB, katG, and ahpC to quickly identify most resistant isolates,
      with a relevant saving of resources, is warranted.

PMID- 10068604
TI  - Serotypes VI and VIII predominate among group B streptococci isolated from
      pregnant Japanese women.
AB  - Infection by group B streptococcus (GBS) is an important cause of bacterial
      disease in neonates, pregnant women, and nonpregnant adults. Whereas serotypes
      Ia, Ib, II, III, and V are most commonly associated with colonization and disease
      in the United States, strains of other serotypes have been isolated from patients
      in Japan. By use of an inhibition ELISA, the serotypes of 73 vaginal colonizing
      GBS strains isolated from healthy pregnant Japanese women were investigated.
      Twenty-six (35.6%) were type VIII, 18 (24.7%) were type VI, and the remaining 29
      were distributed among more traditional serotypes. Strains were also tested by
      immunoblot for the presence of GBS surface proteins. Fifty-three (72.6%) of the
      73 strains expressed one or more laddering GBS proteins. These data show that
      type VI and VIII GBS strains are common vaginal isolates in pregnant Japanese
      women and that one or more laddering proteins are present in most GBS strains.

PMID- 10068605
TI  - Immune responses to recombinant proteins of Mycobacterium leprae.
AB  - Identification of antigenic determinants of the polar immune response in leprosy
      may illuminate both protection and pathogenesis. Thirty subjects were studied (22
      with polar disease and 8 healthy controls who were heavily exposed but disease
      free) by assaying the proliferative, interferon (IFN)-gamma, and antibody
      responses to recombinant antigens of Mycobacterium leprae (10, 28, 36, and 65
      kDa). The 10-kDa antigen elicited IFN-gamma production from all tuberculoid (TT)
      and borderline tuberculoid (BT) patients but little from controls, lepromatous
      (LL), or borderline lepromatous (BL) patients (P<.05). Production of 65-kDa
      specific IFN-gamma was higher in TT/BT than in controls or LL/BL patients
      (P<.006). All subjects produced 65-kDa-specific antibody, but it was higher in
      LL/BL patients than in healthy controls, whose responses were higher than in
      TT/BT subjects (P=.035). The 36-kDa antibody responses were selectively increased
      in LL/BL subjects (P<.02). The intermediate phenotype of the controls suggests
      that M. leprae-specific production of IFN-gamma may contribute to pathology and
      to protection in leprosy.

PMID- 10068606
TI  - Comparison of interferon-gamma, granulocyte colony-stimulating factor, and
      granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated
      hyphal damage of opportunistic fungal pathogens.
AB  - Proinflammatory cytokines have been proposed as adjunctive therapeutic agents to
      enhance the host immune response during infections caused by opportunistic fungi.
      The study compared the differential in vitro priming effects of interferon-gamma
      (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), and granulocyte
      macrophage colony-stimulating factor (GM-CSF) on hyphal damage of opportunistic
      fungi mediated by isolated neutrophils (polymorphonuclear leukocytes, PMNL) and
      buffy coat cells (polymorphonuclear leukocytes/peripheral blood mononuclear
      cells, PMNL/PBMC) from healthy donors. IFN-gamma (1000 U/mL) effectively primed
      both PMNL and PMNL/PBMC for enhanced hyphal damage of Aspergillus fumigatus,
      Fusarium solani, and Candida albicans. G-CSF (100 ng/mL) increased hyphal damage
      mediated by both PMNL and PMNL/PBMC against F. solani, and GM-CSF (100 ng/mL)
      augmented the antifungal activity of PMNL/PBMC against hyphal forms of both F.
      solani and C. albicans. IFN-gamma may be superior to G-CSF or GM-CSF for
      enhancing the microbicidal activity of PMNL and PMNL/PBMC against opportunistic
      fungi.

PMID- 10068607
TI  - HLA class II factors associated with Plasmodium falciparum merozoite surface
      antigen allele families.
AB  - In Plasmodium falciparum malaria, certain human leukocyte antigens (HLA) and the
      parasite's merozoite surface antigens 1 and 2 (MSA-1, MSA-2) have been shown to
      influence the course of the infection. This report is on associations of distinct
      HLA factors with the occurrence of particular MSA families in a group of patients
      with either severe or mild P. falciparum malaria in Gabon. Different
      distributions of HLA-DPB1 alleles were found in the 2 groups. DR *04 alleles were
      observed more frequently among patients with severe malaria. Several alleles of
      different loci were associated with distinct MSA allele families. In addition,
      carriers of the amino acid methionine at position 11 of the DPA1 allele were more
      often infected by MSA-1 K1 parasites and less frequently by MSA-1 RO33 parasites.
      Furthermore, associations of HLA factors with polyclonal infections were found.

PMID- 10068608
TI  - Presence of human herpesvirus 6 DNA in cord blood cells.

PMID- 10068609
TI  - Salmonella abortus equi endotoxin does not affect leptin plasma levels in healthy
      humans.

PMID- 10068610
TI  - Reply 

PMID- 10068612
TI  - Reply 

PMID- 10068611
TI  - Role played by the fibronectin-binding protein SfbI (Protein F1) of Streptococcus
      pyogenes in bacterial internalization by epithelial cells.

PMID- 10068613
TI  - Differences between HLA-B44 and HLA-B60 in patients with smear-positive pulmonary
      tuberculosis and exposed controls.

PMID- 10068615
TI  - A comparison of the nitrogen requirements of the eastern pygmy possum,
      Cercartetus nanus, on a pollen and on a mealworm diet.
AB  - The eastern pygmy possum, Cercartetus nanus, is known to feed both on flower
      products and on invertebrates. This study compares its ability to meet its
      nitrogen requirements on pollen and on insect larvae. Captive C. nanus were fed
      diets in which nitrogen was provided either by Eucalyptus pollen or by the
      mealworm Tenebrio molitor. The apparent digestibility of the nitrogen from both
      sources was high, with a mean value of 76% for the pollen and 73% for the
      mealworms. This was much higher than would have been inferred from the common
      practice of measuring the percentage of empty pollen grains in fecal samples. The
      truly digestible maintenance nitrogen requirements of C. nanus on pollen were
      exceptionally low: 2.6 mg N d-1 compared with 9.5 mg N d-1 on mealworms. The
      value for pollen is the lowest yet recorded for any mammal. The difference
      between the requirements of C. nanus on the two diets appeared to be related to
      the composition of the mealworm and pollen protein. The biological value of the
      pollen nitrogen was exceptionally high for a plant protein, at 72%, whereas the
      biological value of the mealworm nitrogen was only 42%. This suggests that the
      amino acid composition of the pollen corresponded more closely to the
      requirements of C. nanus than the composition of the mealworm protein did. Pollen
      is an excellent source of nitrogen for C. nanus, and it should be considered as a
      potential nitrogen source for other flower-feeding animals.

PMID- 10068616
TI  - Presence of Na-K-ATPase in mitochondria-rich cells in the yolk-sac epithelium of
      larvae of the teleost Oreochromis mossambicus.
AB  - The purpose of this study is to provide biochemical evidence for the functions of
      the mitochondria-rich cell (MR cell) in the yolk-sac epithelium of the developing
      larvae of tilapia Oreochromis mossambicus. Western blotting with the antibody
      (6F) raised against avian Na-K-ATPase alpha1 subunit demonstrated the presence of
      Na-K-ATPase in yolk-sac epithelium of tilapia larvae and about 1. 46-fold more of
      the enzyme in seawater larvae than in freshwater ones. The yolk-sac MR cells were
      immunoreacted to the antibody (alpha5) against the alpha subunit of avian Na-K
      ATPase and were double-labeled with anthroylouabain and dimethylaminostyrylethyl
      pyridiniumiodine, suggesting the existence and activity of Na-K-ATPase in these
      cells. Binding of 3H-ouabain in the yolk sac of seawater larvae was much higher
      than in that of freshwater larvae (4.183+/-0.143 pmol/mg protein versus 1.610+/
      0. 060 pmol/mg protein or 0.0508+/-0.0053 pmol/yolk sac versus 0. 0188+/-0.0073
      pmol/yolk sac). These biochemical results are further evidence that yolk-sac MR
      cells are responsible for a major role in the osmoregulatory mechanism of early
      developmental stages before the function of gills is fully developed.

PMID- 10068617
TI  - Maximal horizontal flight performance of hummingbirds: effects of body mass and
      molt.
AB  - Hovering and fast forward flapping represent two strenuous types of flight that
      differ in aerodynamic power requirement. Maximal capabilities of ruby-throated
      hummingbirds (Archilochus colubris) in hovering and forward flight were compared
      under varying body mass and wing area. The capability to hover in low-density gas
      mixtures was adversely affected by body mass, whereas the capability to fly in a
      wind tunnel did not show any adverse mass effect. Molting birds that lost primary
      flight feathers and reduced wing area also displayed mass loss and loss of
      aerodynamic power and flight speed. This suggests that maximal flight speed is
      insensitive to short-term perturbations of body mass but that molting is
      stressful and reduces the birds' speed and capacity for chase and escape.
      Hummingbirds' flight behavior in confined space was also investigated. Birds
      reduced their speeds flying through a narrow tube to approximately one-fifth of
      that in the wind tunnel and did not display differences under varying body mass
      and wing area. Hence, performance in the flight tube was submaximal and did not
      correlate with performance variation in the wind tunnel. For ruby-throated
      hummingbirds, both maximal mass-specific aerodynamic power derived from hovering
      performance in low-density air media and maximal flight velocity measured in the
      wind tunnel were invariant with body mass.

PMID- 10068618
TI  - Ionoregulatory specializations for exceptional tolerance of ion-poor, acidic
      waters in the neon tetra (Paracheirodon innesi).
AB  - To better understand how fish are able to inhabit dilute waters of low pH, we
      examined ionoregulation in exceptionally acid-tolerant neon tetras (Paracheirodon
      innesi), which are native to the ion-poor, acidic Rio Negro, Amazon. Overall ion
      balance was unaffected by 2-wk exposure to pH 4.0 and 3.5. Measurements of
      unidirectional Na+ fluxes during exposure to pH 3.5 showed that tetras
      experienced only a mild, ionic disturbance of short duration (</=24 h) as a
      result of a stimulation of Na+ efflux. At pH 3.25, Na+ efflux was almost fourfold
      greater (all fish died within 6-8 h). At both pHs, active Na+ uptake was not
      inhibited, and in fact, at pH 3.5, uptake was stimulated. Kinetic analysis of Na+
      uptake at pH 6.5 and 3.5 produced virtually identical low Km values and high
      maximum-transport values. These results confirmed the pH insensitivity of the
      uptake mechanism and revealed a mechanism well designed to operate in the dilute,
      acidic waters of the Rio Negro. Na+ influx was only mildly sensitive to amiloride
      (a Na+ channel blocker), which, along with the pH insensitivity, suggests that
      Na+ uptake may occur by a novel mechanism. Na+ efflux was reduced by addition of
      Ca2+ to the test water at pH 6.5, but the effect disappeared at pH 3.5. Exposure
      to LaCl3 (a strong Ca2+ displacer) also stimulated Na+ efflux. These results
      suggest that Ca2+ plays a role in determining branchial ion permeability at high
      pH but that, at low pH, where Na+ efflux is stimulated, alternate, Ca2+
      independent mechanisms are employed to control Na+ efflux.

PMID- 10068619
TI  - The autonomic nervous control of heart rate in ducks during voluntary diving.
AB  - Autonomic nervous control of heart rate was studied in voluntarily diving ducks
      (Aythya affinis). Ducks were injected with the muscarinic blocker atropine, the
      beta-adrenergic blocker nadolol, the beta-adrenergic agonist isoproterenol, and a
      combination of both atropine and nadolol. Saline injection was used as a control
      treatment. The reduction in heart rate (from the predive level) normally seen
      during a dive was abolished by atropine. Nadolol reduced heart rate during all
      phases of diving activity-predive, dive, and postdive-indicating that sympathetic
      output to the heart was not withdrawn during diving. Isoproterenol increased
      heart rate before, during, and after the dive, although the proportional increase
      in heart rate was not as high during the dive as compared with the increase in
      routine heart rate or heart rate during the predive or postdive phase. The
      parasympathetic system predominates in the control of heart rate during diving
      despite the maintenance of efferent sympathetic influences to the heart, perhaps
      due to accentuated antagonism between the two branches of the autonomic nervous
      system.

PMID- 10068620
TI  - Energy metabolism and body temperature of barn owls fasting in the cold.
AB  - Energetic adaptation to fasting in the cold has been investigated in a nocturnal
      raptor, the barn owl (Tyto alba), during winter. Metabolic rate and body
      temperature (Tb) were monitored in captive birds, (1) after acute exposure to
      different ambient temperatures (Ta), and (2) during a prolonged fast in the cold
      (4 degrees C), to take into account the three characteristic phases of body fuel
      utilization that occur during a long-term but reversible fast. In postabsorptive
      birds, metabolic rate in the thermoneutral zone was 4. 1+/-0.1 W kg-1 and
      increased linearly below a lower critical temperature of 23 degrees C. Metabolic
      rate was 70% above basal at +4 degrees C Ta. Wet thermal conductance was 0.22 W
      kg-1 degrees C-1. During fasting in the cold, the mass-specific resting metabolic
      rate decreased by 16% during the first day (phase I) and remained constant
      thereafter. The amplitude of the daily rhythm in Tb was only moderately increased
      during phase II, with a slight lowering (0. 6 degrees C) in minimal diurnal Tb,
      but rose markedly in phase III with a larger drop (1.4 degrees C) in minimal
      diurnal Tb. Refeeding the birds ended phase III and reversed the observed
      changes. These results indicate that diurnal hypothermia may be used in long-term
      fasting barn owls and could be triggered by a threshold of body lipid depletion,
      according to the shift from lipid to protein fuel metabolism occurring at the
      phase II/phase III transition. The high cost of regulatory thermogenesis and the
      limited use of hypothermia during fasting may contribute to the high mortality of
      barn owls during winter.

PMID- 10068621
TI  - Effects of hypoxia on embryonic development in two Ambystoma and two Rana
      species.
AB  - Oxygen available to amphibian embryos fluctuates widely and is often very low. We
      investigated the effects of oxygen partial pressure (1. 3-16.9 kPa) on embryonic
      development and hatching of two salamander (Ambystoma) and two frog (Rana)
      species. In Ambystoma, chronic hypoxia resulted in slowed development, delayed
      hatching, and embryos that were less developed at the time of hatching. Although
      hypoxia was not lethal to embryos, temporary developmental abnormalities were
      observed in Ambystoma at oxygen partial pressures of 3.8 kPa and below.
      Posthatching survival decreased below 3.3 kPa. In Rana, hypoxia did not affect
      developmental rate, presumably because hatching occurs at a very early stage of
      development relative to Ambystoma. However, Rana embryos hatched sooner in
      hypoxia than in normoxia, resulting in less developed embryos at the time of
      hatching. The results suggest that embryonic hypoxia may negatively affect
      survival and fitness in these species.

PMID- 10068622
TI  - Effects of dietary quality on basal metabolic rate and internal morphology of
      European starlings (Sturnus vulgaris).
AB  - European starlings (Sturnus vulgaris) were fed either a low- or high-quality diet
      to test the effects of dietary quality on basal metabolic rate (BMR) and internal
      morphology. Basal metabolic rate did not differ significantly between the two
      dietary groups, but internal morphology differed greatly. Starlings fed the low
      quality diet had heavier gastrointestinal tracts, gizzards, and livers. Starlings
      fed the high-quality diet had heavier breast muscles. Starlings on the low
      quality diet maintained mass, while starlings on the high-quality diet gained
      mass. Dry matter digestibility and energy digestibility were lower for starlings
      fed the low-quality diet, and their food and water intake were greater than
      starlings on the high-quality diet. The lack of dietary effect on BMR may be the
      result of increased energy expenditure of digestive organs paralleling a
      reduction of energy expenditure of organs and tissues not related to digestion
      (i.e., skeletal muscle). This trade-off in energy allocation among organs
      suggests a mechanism by which organisms may alter BMR in response to a change in
      seasonal variation in food availability.

PMID- 10068623
TI  - In situ and laboratory assessment of heart rate in a Mediterranean limpet using a
      noninvasive technique.
AB  - Heart rate of the Mediterranean limpet Patella caerulea L. was investigated on
      the natural shore and in the laboratory by using a technique based on infrared
      phototransducers. Field recording occurred in the Gulf of Trieste (northern
      Adriatic) during March and June 1997. A consistent dependence of heart rate on
      temperature was observed in limpets both when submerged and when exposed to air
      in the two periods, but thermal acclimation was evident. During spontaneous
      activity at high tide, heart rate increased 1.5-1.7 times the values observed
      during resting in water at corresponding temperatures. The dependence of heart
      rate on temperature (10 degrees, 16 degrees, and 22 degrees C) and size (wet
      weight <1.25 and >1.30 g) in submerged limpets from different populations
      (northern Adriatic and Tyrrhenian) was tested in the laboratory by adopting a
      factorial design. The results showed a marked effect of temperature, body weight,
      and their interaction, independent from the site of origin. Smaller limpets
      showed a linear increase of heart rate in the whole range of temperature tests,
      while in the larger ones the increase between 10 degrees and 16 degrees C was
      greater than between 16 degrees and 22 degrees C. Heart rate decreased with
      increasing body size at control (16 degrees C) and high (22 degrees C)
      temperature, while at lower temperature (10 degrees C) no effect of body size was
      evident. When removed from their home scar, limpets increased heart rate to about
      1.5 times the reference value. Finally, correlation of oxygen consumption with
      heart rate of submerged limpets maintained at a different temperature (10 degrees
      -22 degrees C) was statistically significant.

PMID- 10068624
TI  - Stereological determination of tracheal volume and diffusing capacity of the
      tracheal walls in the stick insect Carausius morosus (Phasmatodea, Lonchodidae).
AB  - First instars of Carausius morosus provide a good model for morphometric
      evaluation of the diffusing capacity between the tracheal system and hemolymph:
      air sacs are lacking, tracheoles do not penetrate the organs and muscles, and
      entire animals can be evaluated electron microscopically without subsampling. The
      tracheal volume makes up 1.3% of the volume of the whole insect excluding
      appendages. We calculated the lateral diffusing capacity for oxygen and carbon
      dioxide for five classes of tracheae according to their diameters, from 0.2
      microm to 35 microm. The harmonic mean thickness of the tracheal epithelium is
      lowest in smallest tracheae and increases with increasing tracheal diameter.
      Although the smallest tracheae make up 70% (O2) and 60% (CO2) of the total
      diffusing capacity, the proximal four classes may also be significant in
      diffusion of oxygen and particularly of carbon dioxide. The suppression of the
      development of respiratory pigments in the evolution of terrestrial insects may
      have increased the relative importance of small tracheal elements for local
      oxygen consumption.

PMID- 10068625
TI  - The role of the nasal passages in the water economy of crested larks and desert
      larks.
AB  - Condensation of water vapor in the exhaled air stream as it passes over
      previously cooled membranes of the nasopharynx is thought to be a mechanism that
      reduces respiratory water loss in mammals and birds. Such a mechanism could be
      important in the overall water economy of these vertebrates, especially those
      species occupying desert habitats. However, this hypothesis was originally based
      on measurements of the temperature of exhaled air (Tex), which provides an
      estimate of water recovered from exhaled air as a proportion of water added on
      inhalation but does not yield a quantitative measure of the reduction in total
      evaporative water loss (TEWL). In this study, we experimentally occluded the
      nares of crested larks (Galerida cristata), a cosmopolitan species, and desert
      larks (Ammomanes deserti), a species restricted to arid habitats, to test the
      hypothesis that countercurrent heat exchange in the nasal passages reduces TEWL.
      Tex of crested larks increased linearly with air temperature, (Ta):
      Tex=8.93+0.793xTa. Following Schmidt-Nielsen and based on measurements of Tex, we
      predicted that crested larks would recover 69%, 49%, 23%, and -5% of the water
      added to the inhaled air at Ta's of 15 degrees, 25 degrees, 35 degrees, and 45
      degrees C, respectively. However, with the nares occluded, crested larks
      increased TEWL by only 27%, 10%, and 6% at Ta's of 15 degrees, 25 degrees, and 35
      degrees C, respectively. At Ta=45 degrees C, TEWL of the crested lark was not
      affected by blocking the nares. In contrast to our expectation, occluding the
      nares of desert larks did not affect their TEWL at any Ta.

PMID- 10068626
TI  - Renal response of euryhaline toad (Bufo viridis) to acute immersion in tap water,
      NaCl, or urea solutions.
AB  - Green toads (Bufo viridis) were acclimated to either tap water, 230 mOsmol NaCl
      kg-1 H2O (saline), 500 mOsmol NaCl kg-1 H2O (high saline), or 500 mmol L-1 urea.
      Renal functions for each acclimation group were studied on conscious animals that
      had one ureter chronically catheterized. Reciprocal immersion of tap-water- and
      saline-acclimated toads in the opposite solution did not stress the animals
      osmotically, and plasma osmolality increased or decreased by no more than 15%.
      However, urine osmolality and ionic composition changed immediately and
      profoundly on exposure to the other solution. Exposure of tap-water-acclimated
      toads to saline decreased urine flow by 30%, whereas the reciprocal immersion led
      to an increase of 30%. Immersion of tap-water-acclimated toads in high saline led
      to immediate cessation of urine flow, whereas immersion of 500 NaCl- or urea
      acclimated toads in tap water led to a large increase in urine flow, with an
      overshoot that lasted 10 h (as a result of either salt or urea diuresis). Urine
      flow then stabilized at a level 5-6 times higher than the value attained at high
      salt environment. On immersion of 500 urea-acclimated toads in 500 NaCl, urine
      flow doubled, accompanied by a change in ion composition, without change in the
      osmolality. In all experimental conditions, plasma potassium concentration was
      maintained within a narrow range. The results show that the toad's kidneys
      contributed efficiently both to osmo- and ionoregulation in a wide range of
      ambient solutions.

PMID- 10068627
TI  - Energy cost of wheel running in house mice: implications for coadaptation of
      locomotion and energy budgets.
AB  - Laboratory house mice (Mus domesticus) that had experienced 10 generations of
      artificial selection for high levels of voluntary wheel running ran about 70%
      more total revolutions per day than did mice from random-bred control lines. The
      difference resulted primarily from increased average velocities rather than from
      increased time spent running. Within all eight lines (four selected, four
      control), females ran more than males. Average daily running distances ranged
      from 4.4 km in control males to 11.6 km in selected females. Whole-animal food
      consumption was statistically indistinguishable in the selected and control
      lines. However, mice from selected lines averaged approximately 10% smaller in
      body mass, and mass-adjusted food consumption was 4% higher in selected lines
      than in controls. The incremental cost of locomotion (grams food/revolution),
      computed as the partial regression slope of food consumption on revolutions run
      per day, did not differ between selected and control mice. On a 24-h basis, the
      total incremental cost of running (covering a distance) amounted to only 4.4% of
      food consumption in the control lines and 7.5% in the selected ones. However, the
      daily incremental cost of time active is higher (15.4% and 13.1% of total food
      consumption in selected and control lines, respectively). If wheel running in the
      selected lines continues to increase mainly by increases in velocity, then
      constraints related to energy acquisition are unlikely to be an important factor
      limiting further selective gain. More generally, our results suggest that, in
      small mammals, a substantial evolutionary increase in daily movement distances
      can be achieved by increasing running speed, without remarkable increases in
      total energy expenditure.

PMID- 10068628
TI  - Controlling for body mass effects: is part-whole correlation important?

PMID- 10068629
TI  - The development and evolution of bristle patterns in Diptera.
AB  - The spatial distribution of sensory bristles on the notum of different species of
      Diptera is compared. Species displaying ancestral features have a simple
      organization of randomly distributed, but uniformly spaced, bristles, whereas
      species thought to be more derived bear patterns in which the bristles are
      aligned into longitudinal rows. The number of rows of large bristles on the
      scutum was probably restricted to four early on in the evolution of cyclorraphous
      Brachyceran flies. Most species have stereotyped patterns based on modifications
      of these four rows. The possible constraints placed upon the patterning
      mechanisms due to growth and moulting within the Diptera are discussed, as well
      as within hemimetabolous insects. The holometabolic life cycle and the setting
      aside of groups of imaginal cells whose function is not required during the
      growth period, may have provided the freedom necessary for the evolution of
      elaborate bristle patterns. We briefly review the current state of knowledge
      concerning the complex genetic pathways regulating achaete-scute gene expression
      and bristle pattern in Drosophila melanogaster, and consider mechanisms for the
      genetic regulation of the bristle patterns of other species of Diptera.

PMID- 10068630
TI  - beta-thymosin is required for axonal tract formation in developing zebrafish
      brain.
AB  - beta-Thymosins are polypeptides that bind monomeric actin and thereby function as
      actin buffers in many cells. We show that during zebrafish development, &bgr;
      thymosin expression is tightly correlated with neuronal growth and
      differentiation. It is transiently expressed in a subset of axon-extending
      neurons, essentially primary neurons that extend long axons, glia and muscle. Non
      neuronal expression in the brain is restricted to a subset of glia surrounding
      newly forming axonal tracts. Skeletal muscle cells in somites, jaw and fin
      express beta-thymosin during differentiation, coinciding with the time of
      innervation. Injection of beta-thymosin antisense RNA into zebrafish embryos
      results in brain defects and impairment of the development of beta-thymosin
      associated axon tracts. Furthermore, irregularities in somite formation can be
      seen in a subset of embryos. Compared to wild-type, antisense-injected embryos
      show slightly weaker and more diffuse engrailed staining at the midbrain
      hindbrain boundary and a strong reduction of Isl-1 labeling in Rohon Beard and
      trigeminal neurons. The decreased expression is not based on a loss of neurons
      indicating that beta-thymosin may be involved in the maintenance of the
      expression of molecules necessary for neuronal differentiation. Taken together,
      our results strongly indicate that beta-thymosin is an important regulator of
      development.

PMID- 10068631
TI  - Dominant effects of RET receptor misexpression and ligand-independent RET
      signaling on ureteric bud development.
AB  - During kidney development, factors from the metanephric mesenchyme induce the
      growth and repeated branching of the ureteric bud, which gives rise to the
      collecting duct system and also induces nephrogenesis. One signaling pathway
      known to be required for this process includes the receptor tyrosine kinase RET
      and co-receptor GFR(&agr;)-1, which are expressed in the ureteric bud, and the
      secreted ligand GDNF produced in the mesenchyme. To examine the role of RET
      signaling in ureteric bud morphogenesis, we produced transgenic mice in which the
      pattern of RET expression was altered, or in which a ligand-independent form of
      RET kinase was expressed. The Hoxb7 promoter was used to express RET throughout
      the ureteric bud branches, in contrast to its normal expression only at the bud
      tips. This caused a variable inhibition of ureteric bud growth and branching
      reminiscent of, but less severe than, the RET knockout phenotype. Manipulation of
      the level of GDNF, in vitro or in vivo, suggested that this defect was due to
      insufficient rather than excessive RET signaling. We propose that RET receptors
      expressed ectopically on ureteric bud trunk cells sequester GDNF, reducing its
      availability to the normal target cells at the bud tips. When crossed to RET
      knockout mice, the Hoxb7/RET transgene, which encoded the RET9 isoform, supported
      normal kidney development in some RET-/- animals, indicating that the other major
      isoform, RET51, is not required in this organ. Expression of a Hoxb7/RET-PTC2
      transgene, encoding a ligand-independent form of RET kinase, caused the
      development of abnormal nodules, outside the kidney or at its periphery,
      containing branched epithelial tubules apparently formed by deregulated growth of
      the ureteric bud. This suggests that RET signaling is not only necessary but is
      sufficient to induce ureteric bud growth, and that the orderly, centripetal
      growth of the bud tips is controlled by the spatially and temporally regulated
      expression of GDNF and RET.

PMID- 10068632
TI  - The auxin-insensitive bodenlos mutation affects primary root formation and apical
      basal patterning in the Arabidopsis embryo.
AB  - In Arabidopsis embryogenesis, the primary root meristem originates from
      descendants of both the apical and the basal daughter cell of the zygote. We have
      isolated a mutant of a new gene named BODENLOS (BDL) in which the primary root
      meristem is not formed whereas post-embryonic roots develop and bdl seedlings
      give rise to fertile adult plants. Some bdl seedlings lacked not only the root
      but also the hypocotyl, thus resembling monopteros (mp) seedlings. In addition,
      bdl seedlings were insensitive to the auxin analogue 2,4-D, as determined by
      comparison with auxin resistant1 (axr1) seedlings. bdl embryos deviated from
      normal development as early as the two-cell stage at which the apical daughter
      cell of the zygote had divided horizontally instead of vertically. Subsequently,
      the uppermost derivative of the basal daughter cell, which is normally destined
      to become the hypophysis, divided abnormally and failed to generate the quiescent
      centre of the root meristem and the central root cap. We also analysed double
      mutants. bdl mp embryos closely resembled the two single mutants, bdl and mp, at
      early stages, while bdl mp seedlings essentially consisted of hypocotyl but did
      form primary leaves. bdl axr1 embryos approached the mp phenotype at later
      stages, and bdl axr1 seedlings resembled mp seedlings. Our results suggest that
      BDL is involved in auxin-mediated processes of apical-basal patterning in the
      Arabidopsis embryo.

PMID- 10068633
TI  - Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis
      in developing myelinating Schwann cells.
AB  - The transcription factors Krox-20 and SCIP each play important roles in the
      differentiation of Schwann cells. However, the genes encoding these two proteins
      exhibit distinct time courses of expression and yield distinct cellular
      phenotypes upon mutation. SCIP is expressed prior to the initial appearance of
      Krox-20, and is transient in both the myelinating and non-myelinating Schwann
      cell lineages; while in contrast, Krox-20 appears approximately 24 hours after
      SCIP and then only within the myelinating lineage, where its expression is stably
      maintained into adulthood. Similarly, differentiation of SCIP-/- Schwann cells
      appears to transiently stall at the promyelinating stage that precedes
      myelination, whereas Krox-20(-/-) cells are, by morphological criteria, arrested
      at this stage. These observations led us to examine SCIP regulation and Schwann
      cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(-/-) Schwann
      cells, SCIP expression is converted from transient to sustained. We further
      observe that both Schwann cell proliferation and apoptosis, which are normal
      features of SCIP+ cells, are also markedly increased late in postnatal
      development in Krox-20 mutants relative to wild type, and that the levels of cell
      division and apoptosis are balanced to yield a stable number of Schwann cells
      within peripheral nerves. These data demonstrate that the loss of Krox-20 in
      myelinating Schwann cells arrests differentiation at the promyelinating stage, as
      assessed by SCIP expression, mitotic activity and susceptibility to apoptosis.

PMID- 10068634
TI  - VEGF deprivation-induced apoptosis is a component of programmed capillary
      regression.
AB  - The pupillary membrane (PM) is a transient ocular capillary network, which can
      serve as a model system in which to study the mechanism of capillary regression.
      Previous work has shown that there is a tight correlation between the cessation
      of blood flow in a capillary segment and the appearance of apoptotic capillary
      cells throughout the segment. This pattern of cell death is referred to as
      synchronous apoptosis (Lang, R. A., Lustig, M., Francois, F., Sellinger, M. and
      Plesken, H. (1994) Development 120, 3395-3404; Meeson, A., Palmer, M., Calfon, M.
      and Lang, R. A. (1996) Development 122, 3929-3938). In the present study, we have
      investigated whether the cause of synchronous apoptosis might be a segmental
      deficiency of either oxygen or a survival factor. Labeling with the compound EF5
      in a normal PM indicated no segmental hypoxia; this argued that oxygen
      deprivation was unlikely to be the cause of synchronous apoptosis. When rat
      plasma was used as a source of survival factors in an in vitro PM explant assay,
      inhibition of vascular endothelial growth factor (VEGF) all but eliminated the
      activity of plasma in suppressing apoptosis. This argued that VEGF was an
      important plasma survival factor. Furthermore, inhibition of VEGF in vivo using
      fusion proteins of the human Flk-1/KDR receptor resulted in a significantly
      increased number of capillaries showing synchronous apoptosis. This provides
      evidence that VEGF is necessary for endothelial cell survival in this system and
      in addition, that VEGF deprivation mediated by flow cessation is a component of
      synchronous apoptosis.

PMID- 10068635
TI  - Differential transcriptional control as the major molecular event in generating
      Otx1-/- and Otx2-/- divergent phenotypes.
AB  - Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene,
      show a limited amino acid sequence divergence. Their embryonic expression
      patterns overlap in spatial and temporal profiles with two major exceptions:
      until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating
      embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal
      telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple
      abnormalities affecting primarily the dorsal telencephalic cortex and components
      of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation
      abnormalities and lack the rostral neuroectoderm corresponding to the forebrain,
      midbrain and rostral hindbrain. In order to define whether these contrasting
      phenotypes reflect differences in expression pattern or coding sequence of Otx1
      and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA.
      Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy
      and corticogenesis abnormalities and showed a significant improvement of
      mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the
      lateral semicircular canal of the inner ear was never recovered, strongly
      supporting an Otx1-specific requirement for the specification of this structure.
      These data indicate an extended functional homology between OTX1 and OTX2
      proteins and provide evidence that, with the exception of the inner ear, in Otx1
      and Otx2 null mice contrasting phenotypes stem from differences in expression
      patterns rather than in amino acid sequences.

PMID- 10068636
TI  - The zebrafish bozozok locus encodes Dharma, a homeodomain protein essential for
      induction of gastrula organizer and dorsoanterior embryonic structures.
AB  - The dorsal gastrula organizer plays a fundamental role in establishment of the
      vertebrate axis. We demonstrate that the zebrafish bozozok (boz) locus is
      required at the blastula stages for formation of the embryonic shield, the
      equivalent of the gastrula organizer and expression of multiple organizer
      specific genes. Furthermore, boz is essential for specification of dorsoanterior
      embryonic structures, including notochord, prechordal mesendoderm, floor plate
      and forebrain. We report that boz mutations disrupt the homeobox gene dharma.
      Overexpression of boz in the extraembryonic yolk syncytial layer of boz mutant
      embryos is sufficient for normal development of the overlying blastoderm,
      revealing an involvement of extraembryonic structures in anterior patterning in
      fish similarly to murine embryos. Epistatic analyses indicate that boz acts
      downstream of beta-catenin and upstream to TGF-beta signaling or in a parallel
      pathway. These studies provide genetic evidence for an essential function of a
      homeodomain protein in beta-catenin-mediated induction of the dorsal gastrula
      organizer and place boz at the top of a hierarchy of zygotic genes specifying the
      dorsal midline of a vertebrate embryo.

PMID- 10068637
TI  - Complex modular cis-acting elements regulate expression of the cardiac specifying
      homeobox gene Csx/Nkx2.5.
AB  - The murine homeobox gene Csx/Nkx2.5 is an evolutionarily highly conserved gene
      related to the Drosophila tinman gene, which specifies cardiac and visceral
      mesoderm. Since Csx/Nkx2.5 plays an essential role in heart development, studying
      its regulation is essential for the better understanding of molecular mechanisms
      of cardiogenesis and the pathogenesis of congenital heart disease in humans. In
      this study, we characterized the murine Csx/Nkx2.5 gene and identified two novel
      untranslated exons, 1a, and 1b, resulting in three different Csx/Nkx2.5
      transcripts. To examine the tissue-specific transcriptional regulation in vivo,
      we analyzed a total of 23 kb of Csx/Nkx2.5 upstream and downstream sequences by
      generating transgenic embryos carrying lacZ reporter constructs containing
      various lengths of flanking sequence. With 14 kb of 5' flanking sequence, lacZ
      expression was observed in the cardiac crescent at E7.5, and in the outflow
      tract, the interatrial groove, the atrioventricular canal and right and left
      ventricles, as well as in pharyngeal floor, thyroid primordia, and stomach at
      E10.5. In adult animals, lacZ expression of the transgene was limited to the
      atrioventricular junction and the subendocardium of the ventricular septum.
      Reducing the size of flanking sequence to 3.3 kb of intron 2 restricted lacZ
      expression to the outflow tract and the basal part of the right ventricle in
      E10.5 embryos. In contrast, the addition of 6 kb of 3' flanking sequence caused
      strong expression of the reporter gene in the entire right ventricle.
      Interestingly, Csx/Nkx2. 5 seems to be negatively regulated by its own gene
      product, because when lacZ was "knocked-in" to replace the entire coding exons,
      lacZ expression was much higher in the heart of homozygous embryos than that in
      the heterozygote. These results indicate that the transcriptional regulatory
      elements of Csx/Nkx 2.5 seems unexpectedly highly modular, and is temporally
      regulated in a dynamic manner by different enhancer regions. Since Csx/Nkx2.5
      like genes are expressed in all species having a heart, their complex modular
      organization with multiple enhancers probably reflects progressive addition of
      regulatory elements during the evolution from a simple heart tube to a complex
      four-chambered organ.

PMID- 10068638
TI  - The netrin receptor frazzled is required in the target for establishment of
      retinal projections in the Drosophila visual system.
AB  - Retinal axons in Drosophila make precise topographic connections with their
      target cells in the optic lobe. Here we investigate the role of the Netrins and
      their receptor Frazzled in the establishment of retinal projections. We find that
      the Netrins, although expressed in the target, are not required for retinal
      projections. Surprisingly, Frazzled, found on both retinal fibers and target
      cells, is required in the target for attracting retinal fibers, while playing at
      best a redundant role in the retinal fibers themselves; this finding demonstrates
      that target attraction is necessary for topographic map formation. Finally, we
      show that Frazzled is not required for the differentiation of cells in the
      target. Our data suggest that Frazzled does not function as a Netrin receptor in
      attracting retinal fibers to the target; nor does it seem to act as a homotypic
      cell adhesion molecule. We favor the possibility that Frazzled in the target
      interacts with a component on the surface of retinal fibers, possibly another
      Netrin receptor.

PMID- 10068639
TI  - Bar homeobox genes are latitudinal prepattern genes in the developing Drosophila
      notum whose expression is regulated by the concerted functions of decapentaplegic
      and wingless.
AB  - In Drosophila notum, the expression of achaete-scute proneural genes and bristle
      formation have been shown to be regulated by putative prepattern genes expressed
      longitudinally. Here, we show that two homeobox genes at the Bar locus (BarH1 and
      BarH2) may belong to a different class of prepattern genes expressed
      latitudinally, and suggest that the developing notum consists of checker-square
      like subdomains, each governed by a different combination of prepattern genes.
      BarH1 and BarH2 are coexpressed in the anterior-most notal region and regulate
      the formation of microchaetae within the region of BarH1/BarH2 expression through
      activating achaete-scute. Presutural macrochaetae formation also requires Bar
      homeobox gene activity. Bar homeobox gene expression is restricted dorsally and
      posteriorly by Decapentaplegic signaling, while the ventral limit of the
      expression domain of Bar homeobox genes is determined by wingless whose
      expression is under the control of Decapentaplegic signaling.

PMID- 10068640
TI  - derriere: a TGF-beta family member required for posterior development in Xenopus.
AB  - TGF-beta signaling plays a key role in induction of the Xenopus mesoderm and
      endoderm. Using a yeast-based selection scheme, we isolated derriere, a novel TGF
      beta family member that is closely related to Vg1 and that is required for normal
      mesodermal patterning, particularly in posterior regions of the embryo. Unlike
      Vg1, derriere is expressed zygotically, with RNA localized to the future endoderm
      and mesoderm by late blastula, and to the posterior mesoderm by mid-gastrula. The
      derriere expression pattern appears to be identical to the zygotic expression
      domain of VegT (Xombi, Brat, Antipodean), and can be activated by VegT as well as
      fibroblast growth factor (FGF). In turn, derriere activates expression of itself,
      VegT and eFGF, suggesting that a regulatory loop exists between these genes.
      derriere is a potent mesoderm and endoderm inducer, acting in a dose-dependent
      fashion. When misexpressed ventrally, derriere induces a secondary axis lacking a
      head, an effect that is due to dorsalization of the ventral marginal zone. When
      misexpressed dorsally, derriere suppresses head formation. derriere can also
      posteriorize neurectoderm, but appears to do so indirectly. Together, these data
      suggest that derriere expression is compatible only with posterior fates. In
      order to assess the in vivo function of derriere, we constructed a dominant
      interfering Derriere protein (Cm-Derriere), which preferentially blocks Derriere
      activity relative to that of other TGFbeta family members. Cm-derriere expression
      in embryos leads to posterior truncation, including defects in blastopore lip
      formation, gastrulation and neural tube closure. Normal expression of anterior
      and hindbrain markers is observed; however, paraxial mesodermal gene expression
      is ablated. This phenotype can be rescued by wild-type derriere and by VegT. Our
      findings indicate that derriere plays a crucial role in mesodermal patterning and
      development of posterior regions in Xenopus.

PMID- 10068641
TI  - Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2
      family.
AB  - Hoxa2 is expressed in cranial neural crest cells that migrate into the second
      branchial arch and is essential for proper patterning of neural-crest-derived
      structures in this region. We have used transgenic analysis to begin to address
      the regulatory mechanisms which underlie neural-crest-specific expression of
      Hoxa2. By performing a deletion analysis on an enhancer from the Hoxa2 gene that
      is capable of mediating expression in neural crest cells in a manner similar to
      the endogenous gene, we demonstrated that multiple cis-acting elements are
      required for neural-crest-specific activity. One of these elements consists of a
      sequence that binds to the three transcription factor AP-2 family members.
      Mutation or deletion of this site in the Hoxa2 enhancer abrogates reporter
      expression in cranial neural crest cells but not in the hindbrain. In both cell
      culture co-transfection assays and transgenic embryos AP-2 family members are
      able to trans-activate reporter expression, showing that this enhancer functions
      as an AP-2-responsive element in vivo. Reporter expression is not abolished in an
      AP-2(alpha) null mutant embryos, suggesting redundancy with other AP-2 family
      members for activation of the Hoxa2 enhancer. Other cis-elements identified in
      this study critical for neural-crest-specific expression include an element that
      influences levels of expression and a conserved sequence, which when multimerized
      directs expression in a broad subset of neural crest cells. These elements work
      together to co-ordinate and restrict neural crest expression to the second
      branchial arch and more posterior regions. Our findings have identified the cis
      components that allow Hoxa2 to be regulated independently in rhombomeres and
      cranial neural crest cells.

PMID- 10068642
TI  - Requirement for the Drosophila COE transcription factor Collier in formation of
      an embryonic muscle: transcriptional response to notch signalling.
AB  - During Drosophila embryogenesis, mesodermal cells are recruited to form a
      stereotyped pattern of about 30 different larval muscles per hemisegment. The
      formation of this pattern is initiated by the specification of a special class of
      myoblasts, called founder cells, that are uniquely able to fuse with neighbouring
      myoblasts. We report here the role of the COE transcription factor Collier in the
      formation of a single muscle, muscle DA3([A])(DA4([T])). Col expression is first
      observed in two promuscular clusters (in segments A1-A7), the two corresponding
      progenitors and their progeny founder cells, but its transcription is maintained
      in only one of these four founder cells, the founder of muscle DA3([A]). This
      lineage-specific restriction depends on the asymmetric segregation of Numb during
      the progenitor cell division and involves the repression of col transcription by
      Notch signalling. In col mutant embryos, the DA3([A]) founder cells form but do
      not maintain col transcription and are unable to fuse with neighbouring
      myoblasts, leading to a loss-of-muscle DA3([A]) phenotype. In wild-type embryos,
      each of the DA3([A])-recruited myoblasts turns on col transcription, indicating
      that the conversion, by the DA3([A]) founder cell, of 'naive' myoblasts to
      express its distinctive pattern of gene expression involves activation of col
      itself. We find that muscles DA3([A]) and DO5([A]) (DA4([T]) and DO5([T])) derive
      from a common progenitor cell. Ectopic expression of Col is not sufficient,
      however, to switch the DO5([A]) to a DA3([A]) fate. Together these results lead
      us to propose that specification of the DA3([A]) muscle lineage requires both Col
      and at least one other transcription factor, supporting the hypothesis of a
      combinatorial code of muscle-specific gene regulation controlling the formation
      and diversification of individual somatic muscles.

PMID- 10068643
TI  - adrift, a novel bnl-induced Drosophila gene, required for tracheal pathfinding
      into the CNS.
AB  - Neurons and glial cells provide guidance cues for migrating neurons. We show here
      that migrating epithelial cells also contact specific neurons and glia during
      their pathfinding, and we describe the first gene required in the process. In
      wild-type Drosophila embryos, the ganglionic tracheal branch navigates a
      remarkably complex path along specific neural and glial substrata, switching
      substrata five times before reaching its ultimate target in the CNS. In adrift
      mutants, ganglionic branches migrate normally along the intersegmental nerve, but
      sporadically fail to switch to the segmental nerve and enter the CNS; they wind
      up meandering along the ventral epidermis instead. adrift encodes a novel nuclear
      protein with an evolutionarily conserved motif. The gene is required in the
      trachea and is expressed in the leading cells of migrating ganglionic branches
      where it is induced by the branchless FGF pathway. We propose that Adrift
      regulates expression of tracheal genes required for pathfinding on the segmental
      nerve, and FGF induction of adrift expression in migrating tracheal cells
      promotes the switch from the intersegmental to the segmental nerve.

PMID- 10068644
TI  - Kinetic analysis of segmentation gene interactions in Drosophila embryos.
AB  - A major challenge for developmental biologists in coming years will be to place
      the vast number of newly identified genes into precisely ordered genetic and
      molecular pathways. This will require efficient methods to determine which genes
      interact directly and indirectly. One of the most comprehensive pathways
      currently under study is the genetic hierarchy that controls Drosophila
      segmentation. Yet, many of the potential interactions within this pathway remain
      untested or unverified. Here, we look at one of the best-characterized components
      of this pathway, the homeodomain-containing transcription factor Fushi tarazu
      (Ftz), and analyze the response kinetics of known and putative target genes. This
      is achieved by providing a brief pulse of Ftz expression and measuring the time
      required for genes to respond. The time required for Ftz to bind and regulate its
      own enhancer, a well-documented interaction, is used as a standard for other
      direct interactions. Surprisingly, we find that both positively and negatively
      regulated target genes respond to Ftz with the same kinetics as autoregulation.
      The rate-limiting step between successive interactions (<10 minutes) is the time
      required for regulatory proteins to either enter or be cleared from the nucleus,
      indicating that protein synthesis and degradation rates are closely matched for
      all of the proteins studied. The matching of these two processes is likely
      important for the rapid and synchronous progression from one class of
      segmentation genes to the next. In total, 11 putative Ftz target genes are
      analyzed, and the data provide a substantially revised view of Ftz roles and
      activities within the segmentation hierarchy.

PMID- 10068645
TI  - The Drosophila SH2-SH3 adapter protein Dock is expressed in embryonic axons and
      facilitates synapse formation by the RP3 motoneuron.
AB  - The Dock SH2-SH3 domain adapter protein, a homolog of the mammalian Nck
      oncoprotein, is required for axon guidance and target recognition by
      photoreceptor axons in Drosophila larvae. Here we show that Dock is widely
      expressed in neurons and at muscle attachment sites in the embryo, and that this
      expression pattern has both maternal and zygotic components. In motoneurons, Dock
      is concentrated in growth cones. Loss of zygotic dock function causes a selective
      delay in synapse formation by the RP3 motoneuron at the cleft between muscles 7
      and 6. These muscles often completely lack innervation in late stage 16 dock
      mutant embryos. RP3 does form a synapse later in development, however, because
      muscles 7 and 6 are normally innervated in third-instar mutant larvae. The
      absence of zygotically expressed Dock also results in subtle defects in a
      longitudinal axon pathway in the embryonic central nervous system. Concomitant
      loss of both maternally and zygotically derived Dock dramatically enhances these
      central nervous system defects, but does not increase the delay in RP3
      synaptogenesis. These results indicate that Dock facilitates synapse formation by
      the RP3 motoneuron and is also required for guidance of some interneuronal axons
      The involvement of Dock in the conversion of the RP3 growth cone into a
      presynaptic terminal may reflect a role for Dock-mediated signaling in remodeling
      of the growth cone's cytoskeleton.

PMID- 10068646
TI  - Anterior organization of the Caenorhabditis elegans embryo by the labial-like Hox
      gene ceh-13.
AB  - The Caenorhabditis elegans lin-39, mab-5 and egl-5 Hox genes specify cell fates
      along the anterior-posterior body axis of the nematode during postembryonic
      development, but little is known about Hox gene functions during embryogenesis.
      Here, we show that the C. elegans labial-like gene ceh-13 is expressed in cells
      of many different tissues and lineages and that the rostral boundary of its
      expression domain is anterior to those of the other Hox genes. By transposon
      mediated mutagenesis, we isolated a zygotic recessive ceh-13 loss-of-function
      allele, sw1, that exhibits an embryonic sublethal phenotype. Lineage analyses and
      immunostainings revealed defects in the organization of the anterior lateral
      epidermis and anterior body wall muscle cells. The epidermal and mesodermal
      identity of these cells, however, is correctly specified. ceh-13(sw1) mutant
      embryos also show fusion and adhesion defects in ectodermal cells. This suggests
      that ceh-13 plays a role in the anterior organization of the C. elegans embryo
      and is involved in the regulation of cell affinities.

PMID- 10068647
TI  - The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth
      and function of particular GABAergic neurons.
AB  - We describe here the functional analysis of the C. elegans LIM homeobox gene lim
      6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS,
      kidney and eye development. lim-6 is expressed in a small number of sensory-,
      inter- and motorneurons, in epithelial cells of the uterus and in the excretory
      system. Loss of lim-6 function affects late events in the differentiation of two
      classes of GABAergic motorneurons which control rhythmic enteric muscle
      contraction. lim-6 is required to specify the correct axon morphology of these
      neurons and also regulates expression of glutamic acid decarboxylase, the rate
      limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity
      and GABA signaling regulate neuroendocrine outputs of the nervous system. In the
      chemosensory system lim-6 regulates the asymmetric expression of a probable
      chemosensory receptor. lim-6 is also required in epithelial cells for uterine
      morphogenesis. We compare the function of lim-6 to those of other LIM homeobox
      genes in C. elegans and suggest that LIM homeobox genes share the common theme of
      controlling terminal neural differentiation steps that when disrupted lead to
      specific neuroanatomical and neural function defects.

PMID- 10068648
TI  - Induction of fetal hemoglobin in sickle cell disease.

PMID- 10068650
TI  - Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid.

PMID- 10068649
TI  - Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell
      disease.
AB  - High levels of fetal hemoglobin (Hb F) protect from many of the complications of
      sickle cell disease and lead to improved survival. Butyrate and other short chain
      fatty acids were previously shown to increase Hb F production in erythroid cells
      in vitro and in animal models in vivo. However, butyrates are also known to
      inhibit the proliferation of many cell types, including erythroid cells.
      Experience with the use of butyrate in animal models and in early clinical trials
      demonstrated that the Hb F response may be lost after prolonged administration of
      high doses of butyrate. We hypothesized that this loss of response may be a
      result of the antiproliferative effects of butyrate. We designed a regimen
      consisting of intermittent or pulse therapy in which butyrate was administered
      for 4 days followed by 10 to 24 days with no drug exposure. This pulse regimen
      induced fetal globin gene expression in 9 of 11 patients. The mean Hb F in this
      group increased from 7.2% to 21.0% (P <.002) after intermittent butyrate therapy
      for a mean duration of 29.9 weeks. This was associated with a parallel increase
      in the number of F cells and F reticulocytes. The total hemoglobin levels also
      increased from a mean of 7.8 g/dL to a mean of 8.8 g/dL (P <.006). The increased
      levels of Hb F were sustained in all responders, including 1 patient who has been
      on pulse butyrate therapy for more than 28 months. This regimen, which resulted
      in a marked and sustained increase in Hb F levels in more than two thirds of the
      adult sickle cell patients enrolled in this study, was well tolerated without
      adverse side effects. These encouraging results require confirmation along with
      an appropriate evaluation of clinical outcomes in a larger number of patients
      with sickle cell disease.

PMID- 10068651
TI  - Gab-family adapter proteins act downstream of cytokine and growth factor
      receptors and T- and B-cell antigen receptors.
AB  - We previously found that the adapter protein Gab1 (110 kD) is tyrosine
      phosphorylated and forms a complex with SHP-2 and PI-3 kinase upon stimulation
      through either the interleukin-3 receptor (IL-3R) or gp130, the common receptor
      subunit of IL-6-family cytokines. In this report, we identified another adapter
      molecule (100 kD) interacting with SHP-2 and PI-3 kinase in response to various
      stimuli. The molecule displays striking homology to Gab1 at the amino acid level;
      thus, we named it Gab2. It contains a PH domain, proline-rich sequences, and
      tyrosine residues that bind to SH2 domains when they are phosphorylated. Gab1 is
      phosphorylated on tyrosine upon stimulation through the thrombopoietin receptor
      (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors
      (TCR and BCR, respectively), in addition to IL-3R and gp130. Tyrosine
      phosphorylation of Gab2 was induced by stimulation through gp130, IL-2R, IL-3R,
      TPOR, SCFR, and TCR. Gab1 and Gab2 were shown to be substrates for SHP-2 in
      vitro. Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated
      ERK2 activation as that of Gab1 did. These data indicate that Gab-family
      molecules act as adapters for transmitting various signals.

PMID- 10068652
TI  - Biallelic and heterozygous point mutations in the runt domain of the
      AML1/PEBP2alphaB gene associated with myeloblastic leukemias.
AB  - The AML1 gene encoding the DNA-binding alpha-subunit in the Runt domain family of
      heterodimeric transcription factors has been noted for its frequent involvement
      in chromosomal translocations associated with leukemia. Using reverse
      transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase
      cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160
      leukemia patients: silent mutations, heterozygous missense mutations, and
      biallelic nonsense or frameshift mutations in 2, 4, and 2 cases, respectively.
      The mutations were all clustered within the Runt domain. Missense mutations
      identified in 3 patients showed neither DNA binding nor transactivation, although
      being active in heterodimerization. These defective missense mutants may be
      relevant to the predisposition or progression of leukemia. On the other hand, the
      biallelic nonsense mutants encoding truncated AML1 proteins lost almost all
      functions examined and may play a role in leukemogenesis leading to acute
      myeloblastic leukemia.

PMID- 10068653
TI  - Vitronectin inhibits the thrombotic response to arterial injury in mice.
AB  - Vitronectin (VN) binds to plasminogen activator inhibitor-1 (PAI-1) and integrins
      and may play an important role in the vascular response to injury by regulating
      fibrinolysis and cell migration. However, the role of VN in the earliest response
      to vascular injury, thrombosis, is not well characterized. The purpose of this
      study was to test the hypothesis that variation in vitronectin expression alters
      the thrombotic response to arterial injury in mice. Ferric chloride (FeCl3)
      injury was used to induce platelet-rich thrombi in mouse carotid arteries. Wild
      type (VN +/+, n = 14) and VN-deficient (VN -/-, n = 15) mice, matched for age and
      gender, were studied. Time to occlusion after FeCl3 injury was determined by
      application of a Doppler flowprobe to the carotid artery. Occlusion times of VN 
      /- mice were significantly shorter than those of VN +/+ mice (6.0 +/- 1.2 minutes
      v 17.8 +/- 2.3 minutes, respectively, P < .001). Histologic analysis of injured
      arterial segments showed that thrombi from VN +/+ and VN -/- mice consisted of
      dense platelet aggregates. In vitro studies of murine VN +/+ and VN -/- platelets
      showed no significant differences in ADP-induced aggregation, but a trend towards
      increased thrombin-induced aggregation in VN -/- platelets. Purified, denatured
      VN inhibited thrombin-induced platelet aggregation, whereas native VN did not.
      Thrombin times of plasma from VN -/- mice (20.5 +/- 2.1 seconds, n = 4) were
      significantly shorter than those of VN +/+ mice (34.2 +/- 6.7 seconds, n = 4, P <
      .01), and the addition of purified VN to VN -/- plasma prolonged the thrombin
      time into the normal range, suggesting that VN inhibits thrombin-fibrinogen
      interactions. PAI-1-deficient mice (n = 6) did not demonstrate significantly
      enhanced arterial thrombosis compared with wild-type mice (n = 6), excluding a
      potential indirect antithrombin function of VN mediated by interactions with PAI
      1 as an explanation for the accelerated thrombosis observed in VN -/- mice. These
      results suggest that vitronectin plays a previously unappreciated antithrombotic
      role at sites of arterial injury and that this activity may be mediated, at least
      in part, by inhibiting platelet-platelet interactions and/or thrombin
      procoagulant activity.

PMID- 10068654
TI  - Cytokine-based tumor cell vaccine is equally effective against parental and
      isogenic multidrug-resistant myeloma cells: the role of cytotoxic T lymphocytes.
AB  - Tumor cells that survive initial courses of chemotherapy may do so by acquiring a
      multidrug-resistant phenotype. This particular mechanism of drug resistance may
      also confer resistance to physiological effectors of apoptosis that could
      potentially reduce the efficacy of immune therapies that use these pathways of
      cell death. We have previously demonstrated high efficacy for a cytokine-based
      tumor cell vaccine in a murine MPC11 myeloma model. In the present study, the
      effects of this vaccination were compared in MPC11 cells and their isogenic
      sublines selected for mdr1/P-glycoprotein (Pgp)-mediated multidrug resistance
      (MDR). Immunization with MPC11 cells expressing granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-12 (IL-12) led to long-lasting
      protection of mice against subcutaneous (sc) challenge with both parental cells
      or their MDR variants. Similarly, immunization with GM-CSF/IL-12-transfected MDR
      sublines caused rejection of transplantation of both parental cells and the MDR
      sublines. Whereas MPC11 cells and their MDR variants were resistant to APO
      1/CD95/Fas ligand, the immunization generated potent granzyme B/perforin
      secreting cytotoxic T lymphocytes (CTLs) that were similarly effective against
      both parental and isogenic MDR cells. We conclude that MDR mediated by mdr1/Pgp
      did not interfere with lysis by pore-forming CTLs. Immunotherapy based on pore
      forming CTLs may be an attractive approach to the treatment of drug-resistant
      myeloma.

PMID- 10068655
TI  - Chemokine and chemokine receptor gene variants and risk of non-Hodgkin's lymphoma
      in human immunodeficiency virus-1-infected individuals.
AB  - Normal B-lymphocyte maturation and proliferation are regulated by chemotactic
      cytokines (chemokines), and genetic polymorphisms in chemokines and chemokine
      receptors modify progression of human immunodeficiency virus-1 (HIV-1) infection.
      Therefore, 746 HIV-1-infected persons were examined for associations of
      previously described stromal cell-derived factor 1 (SDF-1) chemokine and CCR5 and
      CCR2 chemokine receptor gene variants with the risk of B-cell non-Hodgkin's
      lymphoma (NHL). The SDF1-3'A chemokine variant, which is carried by 37% of whites
      and 11% of blacks, was associated with approximate doubling of the NHL risk in
      heterozygotes and roughly a fourfold increase in homozygotes. After a median
      follow-up of 11.7 years, NHL developed in 6 (19%) of 30 SDF1-3'A/3'A homozygotes
      and 22 (10%) of 202 SDF1-+/3'A heterozygotes, compared with 24 (5%) of 514 wild
      type subjects. The acquired immunodeficiency syndrome (AIDS)-protective chemokine
      receptor variant CCR5-triangle up32 was highly protective against NHL, whereas
      the AIDS-protective variant CCR2-64I had no significant effect. Racial
      differences in SDF1-3'A frequency may contribute to the lower risk of HIV-1
      associated NHL in blacks compared with whites. SDF-1 genotyping of HIV-1-infected
      patients may identify subgroups warranting enhanced monitoring and targeted
      interventions to reduce the risk of NHL.

PMID- 10068656
TI  - Human immunodeficiency virus-1-infected macrophages induce inducible nitric oxide
      synthase and nitric oxide (NO) production in astrocytes: astrocytic NO as a
      possible mediator of neural damage in acquired immunodeficiency syndrome.
AB  - Nitric oxide (NO) plays an important role in normal neural cell function.
      Dysregulated or overexpression of NO contributes to neurologic damage associated
      with various pathologies, including human immunodeficiency virus (HIV)-associated
      neurological disease. Previous studies suggest that HIV-infected monocyte-derived
      macrophages (MDM) produce low levels of NO in vitro and that inducible nitric
      oxide synthase (iNOS) is expressed in the brain of patients with neurologic
      disease. However, the levels of NO could not account for the degree of neural
      toxicity observed. In this study, we found that induction of iNOS with
      concomitant production of NO occurred in primary human astrocytes, but not in
      MDM, when astrocytes were cocultured with HIV-1-infected MDM. This coincided with
      decreased HIV replication in infected MDM. Supernatants from cocultures of
      infected MDM and astrocytes also stimulated iNOS/NO expression in astrocytes, but
      cytokines known to induce iNOS expression (interferon-gamma, interleukin-1beta,
      and tumor necrosis factor-alpha) were not detected. In addition, the recombinant
      HIV-1 envelope protein gp41, but not rgp120, induced iNOS in cocultures of
      uninfected MDM and astrocytes. This suggests that astrocytes may be an important
      source of NO production due to dysregulated iNOS expression and may constitute
      one arm of the host response resulting in suppression of HIV-1 replication in the
      brain. It also leads us to speculate that neurologic damage observed in HIV
      disease may ensue from prolonged, high level production of NO.

PMID- 10068657
TI  - Human immunodeficiency virus replication induces monocyte chemotactic protein-1
      in human macrophages and U937 promonocytic cells.
AB  - We have recently described a significant correlation between human
      immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein
      1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the
      acquired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because
      local macrophages (microglia) are the cells predominantly infected in the brain,
      we investigated whether in vitro HIV infection affects MCP-1 production in
      mononuclear phagocytes (MP). MCP-1 secretion and expression were consinstently
      upregulated over constitutive levels in human monocyte-derived macrophages (MDM)
      infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was required
      for this effect, as demonstrated by the absence of chemokine upregulation after
      infection in the presence of 3'-azido-3'-deoxythimidine (AZT) or cell-exposure to
      heat-inactivated (triangle up degrees ) virus. MCP-1 induction was not restricted
      to HIV-1 BaL, but was also observed during productive infection of MDM with two
      primary isolates differing for entry coreceptor usage and of U937 cells with the
      X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1 Tat induced MCP
      1 expression in astrocytes, we also investigated its role in MDM and U937 cells.
      Exogenous Tat induced MCP-1 production from MDM in a concentration-dependent
      manner, however, it was not effective on uninfected U937 cells or on the
      chronically infected U937-derived cell line U1. Transfection of Tat-expressing
      plasmids moderately activated HIV expression in U1 cells, but failed to induce
      MCP-1 expression in this cell line or in uninfected U937 cells. HIV replication
      dependent expression of MCP-1 in MP may be of particular relevance for the
      pathogenesis of HIV infection in nonlymphoid organs such as the brain.

PMID- 10068658
TI  - Multicenter phase III trial to evaluate CD34(+) selected versus unselected
      autologous peripheral blood progenitor cell transplantation in multiple myeloma.
AB  - High-dose chemotherapy followed by autologous transplantation has been shown to
      improve response rates and survival in multiple myeloma and other malignancies.
      However, autografts frequently contain detectable tumor cells. Enrichment for
      stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor
      contamination in phase I/II studies. To more definitively assess the safety and
      efficacy of CD34 selection, a phase III study was completed in 131 multiple
      myeloma patients randomized to receive an autologous transplant with either CD34
      selected or unselected peripheral blood progenitor cells after myeloablative
      therapy. Tumor contamination in the autografts was assessed by a quantitative
      polymerase chain reaction detection assay using patient-specific, complementarity
      determining region (CDR) Ig gene primers before and after CD34 selection. A
      median 3.1 log reduction in contaminating tumor cells was achieved in the CD34
      selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA).
      Successful neutrophil engraftment was achieved in all patients by day 15 and no
      significant between-arm difference for time to platelet engraftment occurred in
      patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg.
      In conclusion, this phase III trial demonstrates that CD34-selection of
      peripheral blood progenitor cells significantly reduces tumor cell contamination
      yet provides safe and rapid hematologic recovery for patients receiving
      myeloablative therapy.

PMID- 10068659
TI  - Effective control of Epstein-Barr virus-related hemophagocytic
      lymphohistiocytosis with immunochemotherapy. Histiocyte Society.
AB  - The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal
      disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH)
      remains uncertain, numerous reports indicate that it can also be fatal in a
      substantial proportion of cases. We therefore assessed the potential of
      immunochemotherapy with a core combination of steroids and etoposide to control
      EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this
      reactive disorder of the mononuclear phagocyte system. Treatment of life
      threatening emergencies was left to the discretion of participating investigators
      and typically included either intravenous Ig or cyclosporin A (CSA). Five
      patients (29%) entered complete remission during the induction phase (1 to 2
      months), whereas 10 others (57%) required additional treatment to achieve this
      status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone
      marrow transplantation. Severe but reversible myelosuppression was a common
      finding; adverse late sequelae were limited to epileptic activity in one child
      and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with
      immunochemotherapy have maintained their complete responses for 4+ to 39+ months
      (median, 15+ months), suggesting a low probability of disease recurrence. These
      results provide a new perspective on EBV-HLH, showing effective control (and
      perhaps cure) of the majority of EBV-HLH cases without bone marrow
      transplantation, using steroids and etoposide, with or without immunomodulatory
      agents.

PMID- 10068660
TI  - The rhesus macaque as an animal model for hemophilia B gene therapy.
AB  - We have determined the 2905 nucleotide sequence of the rhesus macaque factor IX
      complementary DNA (cDNA) and found it to be greater than 95% identical to that of
      the human factor IX cDNA. The cDNA has a large 3' untranslated region like the
      human cDNA, but unlike the human cDNA has two polyadenylation sites 224
      nucleotides apart that are used for transcription of the messenger RNA. The
      deduced amino acid sequence is greater than 97% identical to that of human factor
      IX, differing in only 11 of 461 amino acids in the complete precursor protein. We
      found a single silent polymorphism in the nucleotide sequence at the third
      position of the codon for asparagine at position 167 in the secreted protein
      (AAC/AAT). All residues subject to posttranslational modifications in the human
      protein are also found in the rhesus factor IX sequence. The high degree of
      homology between the rhesus and human factor IX proteins suggested the
      possibility that the human factor IX protein might be nonimmunogenic in the
      rhesus. We tested the immunogenicity of human factor IX in three rhesus macaques
      by repeated intravenous injections of monoclonal antibody-purified, plasma
      derived human factor IX over the course of more than a year and assessed the
      recovery and half-life of the infused protein, as well as in vitro indicators of
      antihuman factor IX antibodies. Human factor IX recovery and half-life remained
      unchanged over the course of a year in the three animals studied, and aPTT mixing
      studies showed no evidence for neutralizing antihuman factor IX antibodies. An
      outbred, nonhuman primate model that permits assessment of the level and duration
      of factor IX expression as well as vector safety would complement the use of
      other (mouse and canine) hemophilia B animal models in current use for the
      development of gene therapy for hemophilia B.

PMID- 10068661
TI  - Transduction of primitive human marrow and cord blood-derived hematopoietic
      progenitor cells with adeno-associated virus vectors.
AB  - We evaluated the capacity of adeno-associated virus (AAV) vectors to transduce
      primitive human myeloid progenitor cells derived from marrow and cord blood in
      long-term cultures and long-term culture-initiating cell (LTC-IC) assays. Single
      colony analyses showed that AAV vectors transduced CD34(+) and CD34(+)38(-)
      clonogenic cells in long-term culture. Gene transfer was readily observed in LTC
      ICs derived from 5-, 8-, and 10-week cultures. Recombinant AAV (rAAV)
      transduction was observed in every donor analyzed, although a wide range of gene
      transfer frequencies (5% to 100%) was noted. AAV transduction of LTC-ICs was
      stable, with week-8 and -10 LTC-ICs showing comparable or better transduction
      relative to week-5 LTC-ICs. Fluorescence in situ hybridization (FISH) analyses
      performed to determine the fate of AAV vectors in transduced cells showed that 9%
      to 28% of CD34(+) and CD34(+)38(-) cells showed stable vector integration as
      evidenced by chromosome-associated signals in metaphase spreads. Comparisons of
      interphase and metaphase FISH suggested that a fraction of cells also contained
      episomal vector at early time points after transduction. Despite the apparent
      loss of the episomal forms with continued culture, the number of metaphases
      containing integrated vector genomes remained stable long term. Transgene
      transcription and placental alkaline phosphatase (PLAP) expression was observed
      in CD34(+), CD34(+)38(-) LTC-ICs in the absence of selective pressure. These
      results suggest that primitive myeloid progenitors are amenable to genetic
      modification with AAV vectors.

PMID- 10068662
TI  - Genetically corrected autologous stem cells engraft, but host immune responses
      limit their utility in canine alpha-L-iduronidase deficiency.
AB  - Canine alpha-L-iduronidase (alpha-ID) deficiency, a model of the human storage
      disorder mucopolysaccharidosis type I (MPS I), is an ideal system in which to
      evaluate the clinical benefit of genetically corrected hematopoietic stem cells.
      We performed adoptive transfer of genetically corrected autologous hematopoietic
      cells in dogs with alpha-ID deficiency. Large volume marrow collections were
      performed on five alpha-ID-deficient dogs. Marrow mononuclear cells in long-term
      marrow cultures (LTMCs) were exposed on three occasions during 3 weeks of culture
      to retroviral vectors bearing the normal canine alpha-ID cDNA. Transduced LTMC
      cells from deficient dogs expressed enzymatically active alpha-ID at 10 to 200
      times the levels seen in normal dogs. An average of 32% of LTMC-derived
      clonogenic hematopoietic cells were provirus positive by polymerase chain
      reaction and about half of these expressed alpha-ID. Approximately 10(7)
      autologous gene-modified LTMC cells/kg were infused into nonmyeloablated
      recipients. Proviral DNA was detected in up to 10% of individual marrow-derived
      hematopoietic colonies and in 0.01% to 1% of blood and marrow leukocytes at up to
      2 to 3 years postinfusion. Despite good evidence for engraftment of provirally
      marked cells, neither alpha-ID enzyme nor alpha-ID transcripts were detected in
      any dog. We evaluated immune responses against alpha-ID and transduced cells.
      Humoral responses to alpha-ID and serum components of the culture media (fetal
      bovine and horse sera and bovine serum albumin) were identified by enzyme-linked
      immunosorbent assay. Cellular immune responses to autologous alpha-ID but not
      neo(r) transduced cells were demonstrated by lymphocyte proliferation assays. To
      abrogate potential immune phenomena, four affected dogs received posttransplant
      cyclosporine A. Whereas immune responses were dampened in these dogs, alpha-ID
      activity remained undetectable. In none of the dogs engrafted with genetically
      corrected cells was there evidence for clinical improvement. Our data suggest
      that, whereas the alpha-ID cDNA may be transferred and maintained in
      approximately 5% of hematopoietic progenitors, the potential of this approach
      appears limited by the levels of provirally derived enzyme that are expressed in
      vivo and by the host's response to cultured and transduced hematopoietic cells
      expressing foreign proteins.

PMID- 10068663
TI  - Human immunodeficiency virus type 1 Vpr alters bone marrow cell function.
AB  - Vpr, a 96 amino acid protein, encoded by the human immunodeficiency virus type I
      (HIV-1), is important for efficient infection of mononuclear phagocytic cells.
      These cells are abundant in whole bone marrow, which can easily be cultured in
      vitro to support hematopoiesis. Our experiments indicate that Vpr plays a role in
      the potent activation of murine and human mononuclear phagocytic cells within a
      hematopoietic microenvironment. In murine cultures, avid erythrophagocytosis is
      triggered by transduction of marrow cells with supernatant derived from PA317
      cells transfected with a murine retroviral delivery vector bearing a Vpr
      expression cassette. Supernatants derived from cells transfected with the same
      vector carrying sequences for the expression of other relevant viral and nonviral
      proteins do not induce erythrophagocytosis to any marked degree. The effect on
      human marrow cells is similar, where treatment promotes adhesion of mononuclear
      phagocytic cells to culture plates in association with other nucleated and
      nonnucleated cells that undergo subsequent engulfment. The differential effects
      of Vpr point and deletion mutants in both marrow culture systems fortify the view
      that the effect is specific to HIV-1 Vpr. Addition of low molar quantities of
      purified Vpr to marrow cultures is also capable of promoting cell adhesion and
      phagocytosis, suggesting that extracellular Vpr is the effector of the
      phenomenon. Accelerated phagocytosis is a hallmark of promonocyte, monocyte, and
      macrophage activation and its occurrence within a hematopoietic microenvironment
      may account for critical in vivo pathogenic features of HIV-1 infection. First,
      activation of mononuclear phagocytes may promote productive viral infection; and
      second, premature phagocytosis could provide, at least in part, a molecular
      explanation for the induction of the idiopathic cytopenias that are typical of
      individuals infected with HIV-1.

PMID- 10068664
TI  - Hematopoietic stem cell tracking in vivo: a comparison of short-term and long
      term repopulating cells.
AB  - We have previously demonstrated that we could separate long-term repopulating
      stem cells from cells that provided radioprotection (short-term repopulating
      cells) on the basis of size and suggested that this might be due to the quiescent
      nature of long-term repopulating cells. To further define the activity of these
      populations, we used a dye (PKH26), which incorporates into the membrane of cells
      and is equally distributed to daughter cells when they divide. We developed an
      assay, which allowed us to retrieve PKH26(+) long-term and short-term
      repopulating cells in the hematopoietic tissues of the recipients posttransplant.
      We were able to recover the labeled cells and determine their cell cycle
      activity, as well as their ability to reconstitute secondary lethally irradiated
      hosts in limiting dilution. The results of our assay suggest that long-term
      repopulating cells are quiescent in the bone marrow (BM) 48 hours after
      transplant. We were able to detect only a few labeled cells in the peripheral
      blood posttransplant and even though cells homed to both the spleen and BM, more
      long-term repopulating cells homed to the marrow and only these cells, which
      homed to the marrow, were capable of reconstituting lethally irradiated secondary
      hosts long-term.

PMID- 10068665
TI  - A novel spliced form of SH2-containing inositol phosphatase is expressed during
      myeloid development.
AB  - SH2-containing Inositol Phosphatase (SHIP) is a 145 kD protein expressed in
      hematopoietic cells. SHIP is phosphorylated on tyrosine after receptor binding by
      several cytokines and has a negative role in hematopoiesis. We cloned a murine
      complementary DNA (cDNA) sequence for an isoform of SHIP with an internal 183
      nucleotide deletion, encoding a protein 61 amino acids shorter than 145 kD SHIP.
      This deletion eliminates potential SH3-domain binding regions and a potential
      binding site for the p85 subunit of Phosphatidylinositol 3-Kinase. Using
      polyclonal anti-SHIP antibodies, we and others have previously observed a 135 kD
      SHIP isoform that is coexpressed with 145 kD SHIP. Here, we used monoclonal
      antibodies raised against the region deleted in the spliced form to show that the
      product of the novel spliced SHIP cDNA is antigenically identical to the 135 kD
      SHIP isoform. Like 145 kD SHIP, 135 kD SHIP expression was induced on
      differentiation of bone marrow cells. After macrophage colony-stimulating factor
      (M-CSF) stimulation of FDC-P1(Fms) myeloid cells, both 145 and 135 kD SHIP forms
      were tyrosine phosphorylated and could be coimmunoprecipitated with antibodies to
      Shc and Grb2. However, experiments showed only a weak association of 135 kD SHIP
      with p85. A potentially analogous 135 kD SHIP species also appears in human
      differentiated leukocytes.

PMID- 10068666
TI  - Cytoplasmic domains of the leukemia inhibitory factor receptor required for STAT3
      activation, differentiation, and growth arrest of myeloid leukemic cells.
AB  - Leukemia inhibitory factor (LIF) induces growth arrest and macrophage
      differentiation of mouse myeloid leukemic cells through the functional LIF
      receptor (LIFR), which comprises a heterodimeric complex of the LIFR subunit and
      gp130. To identify the regions within the cytoplasmic domain of LIFR that
      generate the signals for growth arrest, macrophage differentiation, and STAT3
      activation independently of gp130, we constructed chimeric receptors by linking
      the transmembrane and intracellular regions of mouse LIFR to the extracellular
      domains of the human granulocyte macrophage colony-stimulating factor receptor
      (hGM-CSFR) alpha and betac chains. Using the full-length cytoplasmic domain and
      mutants with progressive C-terminal truncations or point mutations, we show that
      the two membrane-distal tyrosines with the YXXQ motif of LIFR are critical not
      only for STAT3 activation, but also for growth arrest and differentiation of WEHI
      3B D+ cells. A truncated STAT3, which acts in a dominant negative manner was
      introduced into WEHI-3B D+ cells expressing GM-CSFRalpha-LIFR and GM-CSFRbetac
      LIFR. These cells were not induced to differentiate by hGM-CSF. The results
      indicate that STAT3 plays essential roles in the signals for growth arrest and
      differentiation mediated through LIFR.

PMID- 10068667
TI  - Deficient transcription of mouse mast cell protease 4 gene in mutant mice of
      mi/mi genotype.
AB  - The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH
      Zip) protein family of transcription factors (hereafter called MITF). We reported
      that expression of the mouse mast cell protease 5 (MMCP-5) and MMCP-6 genes were
      deficient in cultured mast cells (CMC) derived from mutant mice of mi/mi
      genotype. Despite the reduced expression of both MMCP-5 and MMCP-6, their
      regulation mechanisms were different. Because MMCP-5 is a chymase and MMCP-6 a
      tryptase, there was a possibility that the difference in regulation mechanisms
      was associated with their different characteristics as proteases. We compared the
      regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP
      6. The expression of the MMCP-4 gene was also deficient in mi/mi CMC. The
      overexpression of the normal (+) MITF but not of mi-MITF normalized the poor
      expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF
      in transactivation of the MMCP-4 gene. Although MMCP-4 is chymase as MMCP-5, the
      regulation of MMCP-4 expression was more similar to MMCP-6 than to MMCP-5. We
      also showed the deficient expression of granzyme B and cathepsin G genes in mi/mi
      CMC. Genes encoding granzyme B, cathepsin G, MMCP-4, and MMCP-5 are located on
      chromosome 14. Because all these genes showed deficient expression in mi/mi CMC,
      there is a possibility that MITF might regulate the expression of these genes
      through a locus control region.

PMID- 10068668
TI  - Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human
      megakaryocyte colony formation and proplatelet formation.
AB  - The influence of antiplatelet glycoprotein (GP) antibodies on
      megakaryocytopoiesis in patients with idiopathic or immune thrombocytopenic
      purpura (ITP) has been well studied. However, the influence of GP antibodies on
      proplatelet formation is poorly understood. Here we investigated whether in vitro
      human megakaryocyte colony formation and proplatelet formation are affected by
      various monoclonal antiplatelet GP antibodies (MoAb). The megakaryocyte colony
      formation inhibition assay was performed by methylcellulose culture with
      modifications, using peripheral blood nonadherent mononuclear cells. The
      proplatelet formation inhibition assay was performed by megakaryocytes derived
      from CD34(+) cells, stimulated with thrombopoietin + stem cell factor, which were
      then incubated with antiplatelet GP MoAb for 24 or 48 hours. Anti-GP-Ibalpha MoAb
      (CD42b; HIP1) slightly inhibited megakaryocyte colony formation (P < .05). and
      strongly inhibited proplatelet formation (after 24 hours incubation, P < .0002;
      after 48 hours incubation, P < .0007). Anti-GP-IIb MoAb (CD41; 5B12) inhibited
      only proplatelet formation (only after 24 hours incubation, P <. 03). Anti
      integrin alphavbeta3 MoAb (CD51/CD61; 23C6) only slightly inhibited colony size
      (P < .05). However, anti-GP-IIIa MoAb (CD61; Y2/51) did not inhibit either colony
      formation or proplatelet formation. These results suggest that antiplatelet GP
      MoAbs have differing effects on in vitro megakaryocyte colony formation and
      proplatelet formation.

PMID- 10068669
TI  - Conformational changes in the A3 domain of von Willebrand factor modulate the
      interaction of the A1 domain with platelet glycoprotein Ib.
AB  - Bitiscetin has recently been shown to induce von Willebrand factor (vWF)
      dependent aggregation of fixed platelets (Hamako J, et al, Biochem Biophys Res
      Commun 226:273, 1996). We have purified bitiscetin from Bitis arietans venom and
      investigated the mechanism whereby it promotes a form of vWF that is reactive
      with platelets. In the presence of bitiscetin, vWF binds to platelets in a dose
      dependent and saturable manner. The binding of vWF to platelets involves
      glycoprotein (GP) Ib because it was totally blocked by monoclonal antibody (MoAb)
      6D1 directed towards the vWF-binding site of GPIb. The binding also involves the
      GPIb-binding site of vWF located on the A1 domain because it was inhibited by
      MoAb to vWF whose epitopes are within this domain and that block binding of vWF
      to platelets induced by ristocetin or botrocetin. However, in contrast to
      ristocetin or botrocetin, the binding site of bitiscetin does not reside within
      the A1 domain but within the A3 domain of vWF. Thus, among a series of vWF
      fragments, 125I-bitiscetin only binds to those that overlap the A3 domain, ie,
      SpIII (amino acid [aa] 1-1365), SpI (aa 911-1365), and rvWF-A3 domain (aa 920
      1111). It does not bind to SpII corresponding to the C-terminal part of vWF
      subunit (aa 1366-2050) nor to the 39/34/kD dispase species (aa 480-718) or T116
      (aa 449-728) overlapping the A1 domain. In addition, bitiscetin that does not
      bind to DeltaA3-rvWF (deleted between aa 910-1113) has no binding site ouside the
      A3 domain. The localization of the binding site of bitiscetin within the A3
      domain was further supported by showing that MoAb to vWF, which are specific for
      this domain and block the interaction between vWF and collagen, are potent
      inhibitors of the binding of bitiscetin to vWF and consequently of the bitiscetin
      induced binding of vWF to platelets. Thus, our data support the hypothesis that
      an interaction between the A1 and A3 domains exists that may play a role in the
      function of vWF by regulating the ability of the A1 domain to bind to platelet
      GPIb.

PMID- 10068670
TI  - Inflammatory cytokines and vascular endothelial growth factor stimulate the
      release of soluble tie receptor from human endothelial cells via metalloprotease
      activation.
AB  - Activation of endothelial cells, important in processes such as angiogenesis, is
      regulated by cell surface receptors, including those in the tyrosine kinase (RTK)
      family. Receptor activity, in turn, can be modulated by phosphorylation,
      turnover, or proteolytic release of a soluble extracellular domain. Previously,
      we demonstrated that release of soluble tie-1 receptor from endothelial cells by
      phorbol myristate acetate (PMA) is mediated through protein kinase C and a Ca2+
      dependent protease. In this study, the release of soluble tie-1 was shown to be
      stimulated by inflammatory cytokines and vascular endothelial growth factor
      (VEGF), but not by growth factors such as basic fibroblast growth factor (bFGF)
      or transforming growth factor alpha (TGFalpha). Release of soluble tie by tumor
      necrosis factor alpha (TNFalpha) or VEGF occurred within 10 minutes of
      stimulation and reached maximal levels within 60 minutes. Specificity was shown
      by fluorescence-activated cell sorting (FACS) analysis; endothelial cells
      exhibited a significant decrease in cell surface tie-1 expression in response to
      TNF, whereas expression of epidermal growth factor receptor (EGF-R) and CD31 was
      stable. In contrast, tie-1 expression on megakaryoblastic UT-7 cells was
      unaffected by PMA or TNFalpha. Sequence analysis of the cleaved receptor
      indicated that tie-1 was proteolyzed at the E749/S750 peptide bond in the
      proximal transmembrane domain. Moreover, the hydroxamic acid derivative BB-24
      demonstrated dose-dependent inhibition of cytokine-, PMA-, and VEGF-stimulated
      shedding, suggesting that the tie-1 protease was a metalloprotease. Protease
      activity in a tie-1 peptide cleavage assay was (1) associated with endothelial
      cell membranes, (2) specifically activated in TNFalpha-treated cells, and (3)
      inhibited by BB-24. Additionally, proliferation of endothelial cells in response
      to VEGF, but not bFGF, was inhibited by BB-24, suggesting that the release of
      soluble tie-1 receptor plays a role in VEGF-mediated proliferation. This study
      demonstrated that the release of soluble tie-1 from endothelial cells is
      stimulated by inflammatory cytokines and VEGF through the activation of an
      endothelial membrane-associated metalloprotease.

PMID- 10068671
TI  - Interferon-alpha activates multiple STAT proteins and upregulates proliferation
      associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells.
AB  - Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that has antiviral,
      antiproliferative, and immunoregulatory functions. There is increasing evidence
      that IFN-alpha has an important role in T-cell biology. We have analyzed the
      expression of IL-2Ralpha, c-myc, and pim-1 genes in anti-CD3-activated human T
      lymphocytes. The induction of these genes is associated with interleukin-2 (IL-2)
      induced T-cell proliferation. Treatment of T lymphocytes with IFN-alpha, IL-2, IL
      12, and IL-15 upregulated IL-2Ralpha, c-myc, and pim-1 gene expression. IFN-alpha
      also sensitized T cells to IL-2-induced proliferation, further suggesting that
      IFN-alpha may be involved in the regulation of T-cell mitogenesis. When we
      analyzed the nature of STAT proteins capable of binding to IL-2Ralpha, pim-1, and
      IRF-1 GAS elements after cytokine stimulation, we observed IFN-alpha-induced
      binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements. Yet,
      IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS
      site. IFN-alpha enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a,
      and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the
      GAS elements. Taken together, our results suggest that IFN-alpha, IL-2, IL-12,
      and IL-15 have overlapping activities on human T cells. These findings thus
      emphasize the importance of IFN-alpha as a T-cell regulatory cytokine.

PMID- 10068672
TI  - CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy:
      stimulation of allogeneic versus autologous T cells generates different types of
      effector cells.
AB  - Although spontaneous remissions may rarely occur in B-cell chronic lymphocytic
      leukemia (B-CLL), T cells do generally not develop a clinically significant
      response against B-CLL cells. Because this T-cell anergy against B-CLL cells may
      be caused by the inability of B-CLL cells to present tumor-antigens efficiently,
      we examined the possibility of upregulating critical costimulatory (B7-1 and B7
      2) and adhesion molecules (ICAM-1 and LFA-3) on B-CLL cells to improve antigen
      presentation. The stimulation of B-CLL cells via CD40 by culture on CD40L
      expressing feeder cells induced a strong upregulation of costimulatory and
      adhesion molecules and turned the B-CLL cells into efficient antigen-presenting
      cells (APCs). CD40-activated B-CLL (CD40-CLL) cells stimulated the proliferation
      of both CD4(+) and CD8(+) T cells. Interestingly, stimulation of allogeneic
      versus autologous T cells resulted in the expansion of different effector
      populations. Allogeneic CD40-CLL cells allowed for the expansion of specific
      CD8(+) cytolytic T cells (CTL). In marked contrast, autologous CD40-CLL cells did
      not induce a relevant CTL response, but rather stimulated a CD4(+), Th1-like T
      cell population that expressed high levels of CD40L and released interferon-gamma
      in response to stimulation by CD40-CLL cells. Together, these results support the
      view that CD40 activation of B-CLL cells might reverse T-cell anergy against the
      neoplastic cell clone, although the character of the immune response depends on
      the major histocompatibility complex (MHC) background on which the CLL or tumor
      antigens are presented. These findings may have important implications for the
      design of cellular immunotherapies for B-CLL.

PMID- 10068673
TI  - Involvement of wiskott-aldrich syndrome protein in B-cell cytoplasmic tyrosine
      kinase pathway.
AB  - Bruton's tyrosine kinase (Btk) has been shown to play a role in normal B
      lymphocyte development. Defective expression of Btk leads to human and murine
      immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal
      transduction in B cells is still unclear. This study represents a search for the
      substrate for Btk in vivo. We identified one of the major phosphoproteins
      associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome
      protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which
      is another hereditary immunodeficiency with distinct abnormalities in
      hematopoietic cells. We demonstrated that WASP was transiently tyrosine
      phosphorylated after B-cell antigen receptor cross-linking on B cells, suggesting
      that WASP is located downstream of cytoplasmic tyrosine kinases. An in vivo
      reconstitution system demonstrated that WASP is physically associated with Btk
      and can serve as the substrate for Btk. A protein binding assay suggested that
      the tyrosine-phosphorylation of WASP alters the association between WASP and a
      cellular protein. Furthermore, identification of the phosphorylation site of WASP
      in reconstituted cells allowed us to evaluate the catalytic specificity of Btk,
      the exact nature of which is still unknown.

PMID- 10068674
TI  - Cloning and characterization of a lymphoid-specific, inducible human protein
      tyrosine phosphatase, Lyp.
AB  - Protein tyrosine phosphatases act in conjunction with protein kinases to regulate
      the tyrosine phosphorylation events that control cell activation and
      differentiation. We have isolated a previously undescribed human phosphatase,
      Lyp, that encodes an intracellular 105-kD protein containing a single tyrosine
      phosphatase catalytic domain. The noncatalytic domain contains four proline-rich
      potential SH3 domain binding sites and an NXXY motif that, if phosphorylated, may
      be recognized by phosphotyrosine binding (PTB) domains. Comparison of the Lyp
      amino acid sequence with other known proteins shows 70% identity with the murine
      phosphatase PEP. The human Lyp gene was localized to chromosome 1p13 by
      fluorescence in situ hybridization analysis. We also identified an alternative
      spliced form of Lyp RNA, Lyp2. This isoform encodes a smaller 85-kD protein with
      an alternative C-terminus. The lyp phosphatases are predominantly expressed in
      lymphoid tissues and cells, with Lyp1 being highly expressed in thymocytes and
      both mature B and T cells. Increased Lyp1 expression can be induced by activation
      of resting peripheral T lymphocytes with phytohemagglutinin or anti-CD3. Lyp1 was
      found to be constitutively associated with the proto-oncogene c-Cbl in thymocytes
      and T cells. Overexpression of lyp1 reduces Cbl tyrosine phosphorylation,
      suggesting that it may be a substrate of the phosphatase. Thus, Lyp may play a
      role in regulating the function of Cbl and its associated protein kinases.

PMID- 10068675
TI  - Tandem amino acid repeats from Trypanosoma cruzi shed antigens increase the half
      life of proteins in blood.
AB  - Proteins containing amino acid repeats are widespread among protozoan parasites.
      It has been suggested that these repetitive structures act as immunomodulators,
      but other functional aspects may be of primary importance. We have recently
      suggested that tandem repeats present in Trypanosoma cruzi trans-sialidase
      stabilize the catalytic activity in blood. Because the parasite releases trans
      sialidase, this delayed clearance of the enzyme might have implications in vivo.
      In the present work, the ability of repetitive units from different T. cruzi
      molecules in stabilizing trans-sialidase activity in blood was evaluated. It is
      shown that repeats present on T. cruzi shed proteins (antigens 13 and Shed-Acute
      Phase-Antigen [SAPA]) increase trans-sialidase half-life in blood from 7 to
      almost 35 hours. Conversely, those repeats present in intracellular T. cruzi
      proteins only increase the enzyme half-life in blood up to 15 hours. Despite
      these results, comparative analysis of structural and catalytic properties of
      both groups of chimeric enzymes show no substantial differences. Interestingly,
      antigens 13 and SAPA also increase the persistence in blood of chimeric
      glutathione S-transferases, thus suggesting that this effect is inherent to these
      repeats and independent of the carrier protein. Although the molecular basis of
      this phenomenon is still uncertain, its biotechnological potential can be
      envisaged.

PMID- 10068676
TI  - Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in
      healthy women and women with scleroderma.
AB  - Fetal CD34(+) CD38(+) cells have recently been found to persist in maternal
      peripheral blood for many years after pregnancy. CD34(+) CD38(+) cells are
      progenitor cells that can differentiate into mature immune-competent cells. We
      asked whether long-term fetal microchimerism occurs in T lymphocyte, B
      lymphocyte, monocyte, and natural-killer cell populations of previously pregnant
      women. We targeted women with sons and used polymerase chain reaction for a Y
      chromosome-specific sequence to test DNA extracted from peripheral blood
      mononuclear cells (PBMC) and from CD3, CD19, CD14, and CD56/16 sorted subsets. We
      also asked whether persistent microchimerism might contribute to subsequent
      autoimmune disease in the mother and included women with the autoimmune disease
      scleroderma. Scleroderma has a peak incidence in women after childbearing years
      and has clinical similarities to chronic graft-versus-host disease that occurs
      after allogeneic hematopoietic stem-cell transplantation, known to involve
      chimerism. Sixty-eight parous women were studied for male DNA in PBMC and 20 for
      PBMC subsets. Microchimerism was found in PBMC from 33% (16 of 48) of healthy
      women and 60% (12 of 20) women with scleroderma, P =.046. Microchimerism was
      found in some women in CD3, CD19, CD14, and CD56/16 subsets including up to 38
      years after pregnancy. Microchimerism in PBMC subsets was not appreciably more
      frequent in scleroderma patients than in healthy controls. Overall,
      microchimerism was found in CD3, CD19, and CD14 subsets in approximately one
      third of women and in CD56/16 in one half of women. HLA typing of mothers and
      sons indicated that HLA compatibility was not a requirement for persistent
      microchimerism in PBMC subsets. Fetal microchimerism in the face of HLA disparity
      implies that specific maternal immunoregulatory pathways exist that permit
      persistence but prevent effector function of these cells in normal women.
      Although microchimerism in PBMC was more frequent in women with scleroderma than
      healthy controls additional studies will be necessary to determine whether
      microchimerism plays a role in the pathogenesis of this or other autoimmune
      diseases.

PMID- 10068677
TI  - Spectral karyotype analysis of T-cell acute leukemia.
AB  - Analysis of 15 cases of T-cell acute lymphoblastic leukemia with spectral
      karyotyping (SKY), which can identify all chromosomes simultaneously, clarified
      the chromosome rearrangements in 3 cases and confirmed them in 11 others; no
      abnormal cells were identified in 1 case, which had only 10% abnormal cells. Five
      of the latter cases had a normal karyotype. Thus, the use of SKY substantially
      improves the precision of karyotype analysis of malignant cells, which in turn
      leads to a more accurate assessment of the genotypic abnormalities in those
      cells.

PMID- 10068678
TI  - Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow
      repopulated mice.
AB  - Mutations that activate the N-ras oncogene are among the most frequently detected
      genetic alterations in human acute myeloid leukemias (AMLs), Philadelphia
      chromosome-negative myeloproliferative disorders (MPDs), and myelodysplastic
      syndromes (MDSs). However, because N-ras has not been shown to induce these
      disorders in an in vivo model, the role of N-ras in the evolution of myeloid
      leukemia is unclear. To investigate the potential of N-ras to induce myeloid
      leukemia, lethally irradiated mice were reconstituted with bone marrow (BM) cells
      infected with a retroviral vector carrying activated N-ras. Approximately 60% of
      these mice developed hematopoietic disorders, including severe MPDs resembling
      human chronic myelogenous leukemia (CML) or AML with differentiation (French
      American-British [FAB] classification M2). Other reconstituted mice succumbed to
      hematopoietic defects that were pathologically similar to human MDSs. The latter
      disorders appeared to be due to a myeloid impairment that was demonstrated by
      enumeration of day-12 colony-forming units-spleen (CFU-S) and by in vitro colony
      assays. A high level of apoptosis associated with thymic atrophy and peripheral
      blood (PB) lymphopenia was also evident in N-ras reconstituted mice. Our results
      are consistent with a model in which antiproliferative effects are a primary
      consequence of N-ras mutations and secondary transforming events are necessary
      for the development of myeloid leukemia. This is the first report of an in vivo
      model for N-ras induced MPD and leukemia.

PMID- 10068679
TI  - Effects of novel RAR- and RXR-selective retinoids on myeloid leukemic
      proliferation and differentiation in vitro.
AB  - Retinoids such as all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis
      RA) have an important role in many aspects of proliferation and differentiation
      of hematopoietic cells. They exert their effects by binding to retinoic acid
      receptors (RARs) and/or retinoid X receptors (RXRs). We studied the effects of
      novel retinoids on proliferation and differentiation of HL-60 and NB4 myeloid
      leukemic cells, as well as acute promyelocytic leukemia (APL) cells from
      patients. RXR-selective SR11345 (Retinoid C) had little ability to inhibit the
      clonal growth and to induce the differentiation of either HL-60 or NB4 cells.
      However, SR11276 (Retinoid E), which activated both the RAR and RXR classes, and
      SR11278 (Retinoid D), which activated the RAR subtypes alpha, beta, and gamma,
      could inhibit clonal growth of both cell types, as well as leukemic cells from
      APL patients. The combination of ATRA and either SR11276 or SR11278 additively
      inhibited APL cell proliferation. SR11302 (Retinoid A), with reported anti-AP-1
      activity and no activation of RARs and RXR and SR11363 (Retinoid B), which
      selectively activated RARbeta and gamma, were inactive. The clonal proliferation
      of both HL-60 and NB4 cells that were pulse-exposed to 10(-9) mol/L ATRA,
      SR11276, SR11278, or SR11345 for 3 days, washed, and plated in methylcellulose
      culture were inhibited by 0%, 51%, 21%, and 1% for HL-60 cells and 43%, 41%, 35%,
      and 1% for NB4, respectively, compared with nontreated control cells. When the HL
      60 cells were pulse-exposed to 10(-9) mol/L of either SR11278 or SR11276, plus
      10(-9) mol/L ATRA for 3 days, colony numbers were reduced by 46% and 64%,
      respectively. Induction of leukemic cell differentiation as determined by the
      nitroblue tetrazolium (NBT) assay showed that the combination of 10(-7) mol/L of
      either SR11278 or SR11276 with 10(-7) mol/L ATRA had additive effects on HL-60
      cells, NB4 cells, and fresh APL cells. Induction of CD11b expression on both HL
      60 and NB4 cells occurs during their differentiation. Expression of this antigen
      was synergistically augmented by the combination of either 10(-7) to 10(-8) mol/L
      SR11278 or 10(-7) to 10(-9) mol/L SR11276 with 10(-9) mol/L ATRA compared with
      either analog alone in HL-60 cells. Expression of the novel myeloid specific
      transcription factor C/EBPepsilon was increased by SR11278 and SR11276 in both
      the HL-60 and NB4 cell lines. We conclude that retinoids or combination of
      retinoids with specificities for both RAR and RXR may markedly enhance the
      ability of ATRA to inhibit clonal growth and induce differentiation of HL-60 and
      NB4 leukemic cells. This occurs in the absence of continuous contact with
      retinoids.

PMID- 10068680
TI  - Cyclin A1 expression in leukemia and normal hematopoietic cells.
AB  - Human cyclin A1 is a newly cloned, tissue-specific cyclin that is prominently
      expressed in normal testis. In this study, we showed that cyclin A1 was highly
      expressed in a subset of leukemia samples from patients. The highest frequency of
      cyclin A1 overexpression was observed in acute myelocytic leukemias, especially
      those that were at the promyelocyte (M3) and myeloblast (M2) stages of
      development. Cyclin A1 expression was also detected in normal CD34(+) progenitor
      cells. The expression of cyclin A1 increased when these cells were stimulated to
      undergo myeloid differentiation in vitro. Taken together, our observations
      suggest that cyclin A1 may have a role in hematopoiesis. High levels of cyclin A1
      expression are especially associated with certain leukemias blocked at the
      myeloblast and promyelocyte stages of differentiation.

PMID- 10068681
TI  - Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of
      prognostic significance.
AB  - The BCR-ABL chromosomal translocation is a central event in the pathogenesis of
      chronic myelogenous leukemia (CML). One of the ABL1 promoters (Pa) and the coding
      region of the gene are usually translocated intact to the BCR locus, but the
      translocated promoter appears to be silent in most cases. Recently,
      hypermethylation of Pa was demonstrated in CML and was proposed to mark advanced
      stages of the disease. To study this issue, we measured Pa methylation in CML
      using Southern blot analysis. Of 110 evaluable samples, 23 (21%) had no
      methylation, 17 (15%) had minimal (<15%) methylation, 12 (11%) had moderate
      methylation (15% to 25%), and 58 (53%) had high levels of methylation (>25%) at
      the ABL1 locus. High methylation was more frequent in advanced cases of CML.
      Among the 76 evaluable patients in early chronic phase (ECP), a major cytogenetic
      response with interferon-based therapy was observed in 14 of 34 patients with
      high methylation compared with 19 of 42 among the others (41% v 45%; P value not
      significant). At a median follow-up of 7 years, there was no significant
      difference in survival by ABL1 methylation category. Among patients who achieved
      a major cytogenetic response, low levels of methylation were associated with a
      trend towards improved survival, but this trend did not reach statistical
      significance. Thus, Pa methylation in CML is associated with disease progression
      but does not appear to predict for survival or response to interferon-based
      therapy.

PMID- 10068682
TI  - Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction
      of humoral tolerance in seroconverted patients after repeat administration.
AB  - Alglucerase, a macrophage-targeted enzyme replacement therapy for Gaucher
      disease, has been successfully used for several years to improve clinical
      symptoms and reverse disease progression. As part of an immunosurveillance
      program, 1,122 Gaucher patients were monitored for antibody response to
      glucocerebrosidase, the active component of alglucerase. Seroconversion was
      detected in 142 patients (12.8%) by enzyme-linked immunosorbent assay (ELISA) and
      confirmed by radioimmunoprecipitation. The majority (75%) of the seroconverted
      population had no detectable levels of circulating inhibitory antibody as
      assessed by in vitro inhibition of enzymatic activity of the therapeutic
      molecule. Of the remaining patients with putative inhibitory antibodies, the
      majority had only low levels of serum inhibitory activity, which was transient. A
      very small number of patients were identified as developing true neutralizing
      antibodies, as defined by the development of antibodies that impacted clinical
      efficacy. Many of the patient antibody responses were also diminished with time.
      Eighty-two of the 142 seroconverted patients have stopped producing antibody to
      the molecule and appear tolerized. The mean time for humoral tolerization was 28
      months from initiation of therapy. Of 64 seroconverted patients followed for at
      least 30 months of therapy, the tolerization rate was 93%. These results show
      that although 12.8% of the patients on therapy developed antibodies to the
      molecule, 90% of these patients became tolerized over time.

PMID- 10068683
TI  - The intracellular serpin proteinase inhibitor 6 is expressed in monocytes and
      granulocytes and is a potent inhibitor of the azurophilic granule protease,
      cathepsin G.
AB  - The monocyte and granulocyte azurophilic granule proteinases elastase, proteinase
      3, and cathepsin G are implicated in acute and chronic diseases thought to result
      from an imbalance between the secreted proteinase(s) and circulating serpins such
      as alpha1-proteinase inhibitor and alpha1-antichymotrypsin. We show here that the
      intracellular serpin, proteinase inhibitor 6 (PI-6), is present in monocytes,
      granulocytes, and myelomonocytic cell lines. In extracts from these cells, PI-6
      bound an endogenous membrane-associated serine proteinase to form an sodium
      dodecyl sulfate (SDS)-stable complex. Using antibodies to urokinase, elastase,
      proteinase 3, or cathepsin G, we demonstrated that the complex contains cathepsin
      G. Native cathepsin G and recombinant PI-6 formed an SDS-stable complex in vitro
      similar in size to that observed in the extracts. Further kinetic analysis
      demonstrated that cathepsin G and PI-6 rapidly form a tight 1:1 complex (ka = 6.8
      +/- 0.2 x 10(6) mol/L-1s-1 at 17 degrees C; Ki = 9.2 +/- 0.04 x 10(-10) mol/L).
      We propose that PI-6 complements alpha1-proteinase inhibitor and alpha1
      antichymotrypsin (which control extracellular proteolysis) by neutralizing
      cathepsin G that leaks into the cytoplasm of monocytes or granulocytes during
      biosynthesis or phagocytosis. Control of intracellular cathepsin G may be
      particularly important, because it has recently been shown to activate the
      proapoptotic proteinase, caspase-7.

PMID- 10068684
TI  - Missense mutations in the gp91-phox gene encoding cytochrome b558 in patients
      with cytochrome b positive and negative X-linked chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a disorder of host defense due to genetic
      defects of the superoxide (O2-) generating NADPH oxidase in phagocytes. A
      membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22
      phox, is a critical component of the oxidase. The X-linked form of the disease is
      due to defects in the gp91-phox gene. We report here biochemical and genetic
      analyses of patients with typical and atypical X-linked CGD. Immunoblots showed
      that neutrophils from one patient had small amounts of p22-phox and gp91-phox and
      a low level of O2- forming oxidase activity, in contrast to the complete absence
      of both subunits in two patients with typical CGD. Using polymerase chain
      reactions (PCR) on cDNA and genomic DNA, we found novel missense mutations of
      gp91-phox in the two typical patients and a point mutation in the variant CGD, a
      characteristic common to two other patients with similar variant CGD reported
      previously. Spectrophotometric analysis of the neutrophils from the variant
      patient provided evidence for the presence of heme of cytochrome b558. Recently,
      we reported another variant CGD with similar amounts of both subunits, but
      without oxidase activity or the heme spectrum. A predicted mutation at amino acid
      101 in gp91-phox was also confirmed in this variant CGD by PCR of the genomic
      DNA. These results on four patients, including those with two variant CGD, are
      discussed with respect to the missense mutated sites and the heme binding ligands
      in gp91-phox.

PMID- 10068685
TI  - Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase
      allelic variant with low expression accounts for clinical manifestation.
AB  - Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of heme
      biosynthesis characterized by partial decrease in ferrochelatase (FECH; EC
      4.99.1.1) activity with protoporphyrin overproduction and consequent painful skin
      photosensitivity and rarely liver disease. EPP is normally inherited in an
      autosomal dominant pattern with low clinical penetrance; the many different
      mutations that have been identified are restricted to one FECH allele, with the
      other one being free of any mutations. However, clinical manifestations of
      dominant EPP cannot be simply a matter of FECH haploinsufficiency, because
      patients have enzyme levels that are lower than the expected 50%. From RNA
      analysis in one family with dominant EPP, we recently suggested that clinical
      expression required coinheritance of a normal FECH allele with low expression and
      a mutant FECH allele. We now show that (1) coinheritance of a FECH gene defect
      and a wild-type low-expressed allele is generally involved in the clinical
      expression of EPP; (2) the low-expressed allelic variant was strongly associated
      with a partial 5' haplotype [-251G IVS1-23T IVS2microsatA9] that may be ancestral
      and was present in an estimated 10% of a control group of Caucasian origin; and
      (3) haplotyping allows the absolute risk of developing the disease to be
      predicted for those inheriting FECH EPP mutations. EPP may thus be considered as
      an inherited disorder that does not strictly follow recessive or dominant rules.
      It may represent a model for phenotype modulation by mild variation in expression
      of the wild-type allele in autosomal dominant diseases.

PMID- 10068686
TI  - Identification of the poly(C) binding protein in the complex associated with the
      3' untranslated region of erythropoietin messenger RNA.
AB  - Hypoxia regulates expression of erythropoietin (EPO), a glycoprotein that
      stimulates erythrocytosis, at the level of transcription and also possibly at the
      level of messenger RNA (mRNA) stability. A pyrimidine-rich region within the EPO
      mRNA 3' untranslated region was implicated in regulation of EPO mRNA stability
      element and shown to bind protein factors. In the present study we wished to
      identify the protein factor binding to the pyrimidine-rich sequence in the EPO
      mRNA stability element. Using mobility shift assays, ultraviolet light cross
      linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), and electroelution of protein factors from the gel slices corresponding to
      the ribonucleoprotein complexes, we found that two isoforms of a 40 kD poly(C)
      binding protein (PCBP, also known as alphaCP or hnRNPE), PCBP1, and PCBP2 are
      present in that complex. In Hep3B or HepG2 cells hypoxia induces neither
      expression of PCBP nor formation of the ribonucleoprotein complex associated with
      EPO mRNA that involves PCBP.

PMID- 10068687
TI  - Structural and functional consequences of antigenic modulation of red blood cells
      with methoxypoly(ethylene glycol).
AB  - We previously showed that the covalent modification of the red blood cell (RBC)
      surface with methoxypoly(ethylene glycol) [mPEG; MW approximately 5 kD] could
      significantly attenuate the immunologic recognition of surface antigens. However,
      to make these antigenically silent RBC a clinically viable option, the mPEG
      modified RBC must maintain normal cellular structure and functions. To this end,
      mPEG-derivatization was found to have no significant detrimental effects on RBC
      structure or function at concentrations that effectively blocked antigenic
      recognition of a variety of RBC antigens. Importantly, RBC lysis, morphology, and
      hemoglobin oxidation state were unaffected by mPEG-modification. Furthermore, as
      shown by functional studies of Band 3, a major site of modification, PEG-binding
      does not affect protein function, as evidenced by normal SO4- flux. Similarly,
      Na+ and K+ homeostasis were unaffected. The functional aspects of the mPEG
      modified RBC were also maintained, as evidenced by normal oxygen binding and
      cellular deformability. Perhaps most importantly, mPEG-derivatized mouse RBC
      showed normal in vivo survival ( approximately 50 days) with no sensitization
      after repeated transfusions. These data further support the hypothesis that the
      covalent attachment of nonimmunogenic materials (eg, mPEG) to intact RBC may have
      significant application in transfusion medicine, especially for the chronically
      transfused and/or allosensitized patient.

PMID- 10068688
TI  - Imagene: an integrated computer environment for sequence annotation and analysis.
AB  - MOTIVATION: To be fully and efficiently exploited, data coming from sequencing
      projects together with specific sequence analysis tools need to be integrated
      within reliable data management systems. Systems designed to manage genome data
      and analysis tend to give a greater importance either to the data storage or to
      the methodological aspect, but lack a complete integration of both components.
      RESULTS: This paper presents a co-operative computer environment (called
      Imagenetrade mark) dedicated to genomic sequence analysis and annotation. Imagene
      has been developed by using an object-based model. Thanks to this representation,
      the user can directly manipulate familiar data objects through icons or lists.
      Imagene also incorporates a solving engine in order to manage analysis tasks. A
      global task is solved by successive divisions into smaller sub-tasks. During
      program execution, these sub-tasks are graphically displayed to the user and may
      be further re-started at any point after task completion. In this sense, Imagene
      is more transparent to the user than a traditional menu-driven package. Imagene
      also provides a user interface to display, on the same screen, the results
      produced by several tasks, together with the capability to annotate these results
      easily. In its current form, Imagene has been designed particularly for use in
      microbial sequencing projects. AVAILABILITY: Imagene best runs on SGI (Irix 6.3
      or higher) workstations. It is distributed free of charge on a CD-ROM, but
      requires some Ilog licensed software to run. Some modules also require separate
      license agreements. Please contact the authors for specific academic conditions
      and other Unix platforms. CONTACT: imagene home page:
      http://wwwabi.snv.jussieu.fr/imagene

PMID- 10068689
TI  - Stem Trace: an interactive visual tool for comparative RNA structure analysis.
AB  - MOTIVATION: Stem Trace is one of the latest tools available in STRUCTURELAB, an
      RNA structure analysis computer workbench. The paradigm used in STRUCTURELAB
      views RNA structure determination as a problem of dealing with a database of a
      large number of computationally generated structures. Stem Trace provides the
      capability to analyze this data set in a novel, visually driven, interactive and
      exploratory way. In addition to providing graphs at a high level of ion, it is
      also connected with complementary visualization tools which provide orthogonal
      views of the same data, as well as drawing of structures represented by a stem
      trace. Thus, on top of being an analysis tool, Stem Trace is a graphical user
      interface to an RNA structural information database. RESULTS: We illustrate Stem
      Trace's capabilities with several examples of the analysis of RNA folding data
      performed on 24 strains of HIV-1, HIV-2 and SIV sequences around the HIV
      dimerization region. This dimer linkage site has been found to play a role in
      encapsidation, reverse transcription, recombination, and inhibition of
      translation. Our examples show how Stem Trace elucidates preservation of
      structures in this region across the various strains of HIV. AVAILABILITY: The
      program can be made available upon request. It runs on SUN, SGI and DEC (Compaq)
      Unix workstations.

PMID- 10068690
TI  - RNA movies: visualizing RNA secondary structure spaces.
AB  - MOTIVATION: RNA Movies is a system for the visualization of RNA secondary
      structure spaces. Its input is a script consisting of primary and secondary
      structure information. From this script, the system fully automatically generates
      animated graphical structure representations. In this way, it creates the
      impression of an RNA molecule exploring its own two-dimensional structure space.
      RESULTS: RNA Movies has been used to generate animations of a switching structure
      in the spliced leader RNA of Leptomonas collosoma and sequential foldings of
      potato spindle tuber viroid transcripts. AVAILABILITY: Demonstrations of the
      animations mentioned in this paper can be viewed on our Bioinformatics web server
      under the following address: http://BiBiServ.TechFak.Uni-Bielefeld.
      DE/rnamovies/. The RNA Movies software is available upon request from the
      authors.

PMID- 10068691
TI  - Bayesian inference on biopolymer models.
AB  - MOTIVATION: Most existing bioinformatics methods are limited to making point
      estimates of one variable, e.g. the optimal alignment, with fixed input values
      for all other variables, e.g. gap penalties and scoring matrices. While the
      requirement to specify parameters remains one of the more vexing issues in
      bioinformatics, it is a reflection of a larger issue: the need to broaden the
      view on statistical inference in bioinformatics. RESULTS: The assignment of
      probabilities for all possible values of all unknown variables in a problem in
      the form of a posterior distribution is the goal of Bayesian inference. Here we
      show how this goal can be achieved for most bioinformatics methods that use
      dynamic programming. Specifically, a tutorial style description of a Bayesian
      inference procedure for segmentation of a sequence based on the heterogeneity in
      its composition is given. In addition, full Bayesian inference algorithms for
      sequence alignment are described. AVAILABILITY: Software and a set of
      transparencies for a tutorial describing these ideas are available at
      http://www.wadsworth.org/res&res/bioinfo/

PMID- 10068692
TI  - Using imperfect secondary structure predictions to improve molecular structure
      computations.
AB  - MOTIVATION: Until ab initio structure prediction methods are perfected, the
      estimation of structure for protein molecules will depend on combining multiple
      sources of experimental and theoretical data. Secondary structure predictions are
      a particularly useful source of structural information, but are currently only
      approximately 70% correct, on average. Structure computation algorithms which
      incorporate secondary structure information must therefore have methods for
      dealing with predictions that are imperfect. EXPERIMENTS PERFORMED: We have
      modified our algorithm for probabilistic least squares structural computations to
      accept 'disjunctive' constraints, in which a constraint is provided as a set of
      possible values, each weighted with a probability. Thus, when a helix is
      predicted, the distances associated with a helix are given most of the weight,
      but some weights can be allocated to the other possibilities (strand and coil).
      We have tested a variety of strategies for this weighting scheme in conjunction
      with a baseline synthetic set of sparse distance data, and compared it with
      strategies which do not use disjunctive constraints. RESULTS: Naive
      interpretations in which predictions were taken as 100% correct led to poor
      quality structures. Interpretations that allow disjunctive constraints are quite
      robust, and even relatively poor predictions (58% correct) can significantly
      increase the quality of computed structures (almost halving the RMS error from
      the known structure). CONCLUSIONS: Secondary structure predictions can be used to
      improve the quality of three-dimensional structural computations. In fact, when
      interpreted appropriately, imperfect predictions can provide almost as much
      improvement as perfect predictions in three-dimensional structure calculations.

PMID- 10068693
TI  - A fast, stochastic threading algorithm for proteins.
AB  - MOTIVATION: Sequences for new proteins are being determined at a rapid rate, as a
      result of the Human Genome Project, and related genome research. The ability to
      predict the three-dimensional structure of proteins from sequence alone would be
      useful in discovering and understanding their function. Threading, or fold
      recognition, aims to predict the tertiary structure of a protein by aligning its
      amino acid sequence with a large number of structures, and finding the best fit.
      This approach depends on obtaining good performance from both the scoring
      function, which simulates the free energy for given trial alignments, and the
      threading algorithm, which searches for the lowest-score alignment. It appears
      that current scoring functions and threading algorithms need improvement.
      RESULTS: This paper presents a new threading algorithm. Numerical tests
      demonstrate that it is more powerful than two popular approximate algorithms, and
      much faster than exact methods.

PMID- 10068694
TI  - E-CELL: software environment for whole-cell simulation.
AB  - MOTIVATION: Genome sequencing projects and further systematic functional analyses
      of complete gene sets are producing an unprecedented mass of molecular
      information for a wide range of model organisms. This provides us with a detailed
      account of the cell with which we may begin to build models for simulating
      intracellular molecular processes to predict the dynamic behavior of living
      cells. Previous work in biochemical and genetic simulation has isolated well
      characterized pathways for detailed analysis, but methods for building
      integrative models of the cell that incorporate gene regulation, metabolism and
      signaling have not been established. We, therefore, were motivated to develop a
      software environment for building such integrative models based on gene sets, and
      running simulations to conduct experiments in silico. RESULTS: E-CELL, a modeling
      and simulation environment for biochemical and genetic processes, has been
      developed. The E-CELL system allows a user to define functions of proteins,
      protein-protein interactions, protein-DNA interactions, regulation of gene
      expression and other features of cellular metabolism, as a set of reaction rules.
      E-CELL simulates cell behavior by numerically integrating the differential
      equations described implicitly in these reaction rules. The user can observe,
      through a computer display, dynamic changes in concentrations of proteins,
      protein complexes and other chemical compounds in the cell. Using this software,
      we constructed a model of a hypothetical cell with only 127 genes sufficient for
      transcription, translation, energy production and phospholipid synthesis. Most of
      the genes are taken from Mycoplasma genitalium, the organism having the smallest
      known chromosome, whose complete 580 kb genome sequence was determined at TIGR in
      1995. We discuss future applications of the E-CELL system with special respect to
      genome engineering. AVAILABILITY: The E-CELL software is available upon request.
      SUPPLEMENTARY INFORMATION: The complete list of rules of the developed cell model
      with kinetic parameters can be obtained via our web site at: http://e-cell.org/.

PMID- 10068695
TI  - Genetic Simulation Library.
AB  - SUMMARY: The Genetic Simulation Library (GSL) is a set of C++ programs and
      classes that can be used in individual-based simulation models of plant and
      animal populations. The classes in this library build representations of genes
      for a wide variety of different types of organisms, from asexually reproducing
      single-cell organisms to chromosome-structured sexually reproducing species.
      AVAILABILITY: http://www.csi.uoregon.edu/projects/genetics/GSL . Free for non
      commercial applications; others should contact the author.

PMID- 10068696
TI  - BAliBASE: a benchmark alignment database for the evaluation of multiple alignment
      programs.
AB  - SUMMARY: BAliBASE is a database of manually refined multiple sequence alignments
      categorized by core blocks of conservation sequence length, similarity, and the
      presence of insertions and N/C-terminal extensions. AVAILABILITY: From http://www
      igbmc. u-strasbg.fr/BioInfo/BAliBASE/index.html

PMID- 10068698
TI  - Volume 202, number 2 (1998), in article no. DB989012, "Tissues exhibiting
      inhibiory and repulsive activities during the initial stages of neurite outgrowth
      from the dorsal root ganglion in the chick Embryo," by keiko nakamoto and takashi
      shiga, pages 304-314 

PMID- 10068697
TI  - Application of distance geometry to 3D visualization of sequence relationships.
AB  - SUMMARY: We describe the application of distance geometry methods to the three
      dimensional visualization of sequence relationships, with examples for mumps
      virus SH gene cDNA and prion protein sequences. Sequence-sequence distance
      measures may be obtained from either a multiple sequence alignment or from sets
      of pairwise alignments. AVAILABILITY: C/Perl code and HTML/VRML files from
      http://www.nibsc.ac.uk/dg3dseq/

PMID- 10068699
TI  - Reply 

PMID- 10068700
TI  - Internet resource for physicians who treat patients with HIV.

PMID- 10068701
TI  - Childhood obesity: time for action, not complacency.

PMID- 10068702
TI  - Problem sleepiness: an often unrecognized condition.

PMID- 10068703
TI  - ACOG/AAFP guidelines for obstetrics and gynecology.

PMID- 10068704
TI  - Screening for inborn errors of metabolism in children.

PMID- 10068706
TI  - Diagnosis and treatment of the acute scrotum.
AB  - Testicular torsion must be considered in any patient who complains of acute
      scrotal pain and swelling. Torsion of the testis is a surgical emergency because
      the likelihood of testicular salvage decreases as the duration of torsion
      increases. Conditions that may mimic testicular torsion, such as torsion of a
      testicular appendage, epididymitis, trauma, hernia, hydrocele, varicocele and
      Schonlein-Henoch purpura, generally do not require immediate surgical
      intervention. The cause of an acute scrotum can usually be established based on a
      careful history, a thorough physical examination and appropriate diagnostic
      tests. The onset, character and severity of symptoms must be determined. The
      physical examination should include inspection and palpation of the abdomen,
      testis, epididymis, scrotum and inguinal region. Urinalysis should always be
      performed, but scrotal imaging is necessary only when the diagnosis remains
      unclear. Once the correct diagnosis is established, treatment is usually
      straightforward.

PMID- 10068707
TI  - Liver disease in pregnancy.
AB  - Acute viral hepatitis is the most common cause of jaundice in pregnancy. The
      course of acute hepatitis is unaffected by pregnancy, except in patients with
      hepatitis E and disseminated herpes simplex infections, in which maternal and
      fetal mortality rates are significantly increased. Chronic hepatitis B or C
      infections may be transmitted to neonates; however, hepatitis B virus
      transmission is effectively prevented with perinatal hepatitis B vaccination and
      prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent
      of pregnancies; complications can safely be treated with surgery. Women with
      chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during
      pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver
      enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and
      hepatic infarction and rupture. These rare diseases result in increased maternal
      and fetal mortality. Treatment involves prompt delivery, whereupon the liver
      disease quickly reverses. Therapy with penicillamine, trientine, prednisone or
      azathioprine can be safely continued during pregnancy.

PMID- 10068708
TI  - Evaluating patients for return to work.
AB  - The family physician is often instrumental in the process of returning a patient
      to the workplace after injury or illness. Initially, the physician must gain an
      understanding of the job's demands through detailed discussions with the patient,
      the patient's work supervisor or the occupational medicine staff at the patient's
      place of employment. Other helpful sources of information include job demand
      analysis evaluations and the Dictionary of Occupational Titles. With an adequate
      knowledge of job requirements and patient limitations, the physician should
      document specific workplace restrictions, ensuring a safe and progressive reentry
      to work. Occupational rehabilitation programs such as work hardening may be
      prescribed, if necessary. If the physician is unsure of the patient's status, a
      functional capacity evaluation should be considered. The family physician should
      also be familiar with the Americans with Disabilities Act as it applies to the
      patient's "fitness" to perform the "essential tasks" of the patient's job.

PMID- 10068709
TI  - 'Common' uncommon anemias.
AB  - Of the uncommon anemias, "common" types include the anemia of renal disease,
      thalassemia, myelodysplastic syndrome and the anemia of chronic disease. These
      conditions may be suggested by the clinical presentation, laboratory test values
      and peripheral blood smear, or by failure of the anemia to respond to iron
      supplements or nutrient replacement. The principal cause of the anemia of renal
      disease is a decreased production of red blood cells related to a relative
      deficiency of erythropoietin. When treatment is required, erythropoietin is
      administered, often with iron supplementation. In the anemia of chronic disease,
      impaired iron transport decreases red blood cell production. Treatment is
      predominantly directed at the underlying condition. Since iron stores are usually
      normal, iron administration is not beneficial. Thalassemia minor results from a
      congenital abnormality of hemoglobin synthesis. The disorder may masquerade as
      mild iron deficiency anemia, but iron therapy and transfusions are often not
      indicated. In the myelodysplastic syndrome, blood cell components fail to mature,
      and the condition may progress to acute nonlymphocytic leukemia. The rate of
      progression depends on the subtype of myelodysplasia, but the leukemia is usually
      resistant to therapy.

PMID- 10068710
TI  - Evaluation and treatment of childhood obesity.
AB  - The prevalence of childhood obesity in the United States has risen dramatically
      in the past several decades. Although 25 to 30 percent of children are affected,
      this condition is underdiagnosed and undertreated. Hormonal and genetic factors
      are rarely the cause of childhood obesity; unnecessary diagnostic evaluations can
      be avoided with a careful history and physical examination. Because obese
      children may suffer life-long physical and emotional consequences, it is
      imperative to discuss prevention with parents during well-child examinations. All
      obese children should be screened for cardiac risk factors, as well as for
      possible orthopedic, dermatologic and psychiatric sequelae. Treatment should be
      initiated when the trend in increasing weight obviously surpasses the trend in
      increasing height. Treatment plans should include reasonable weight-loss goals,
      dietary and physical activity management, behavior modification and family
      involvement, which may include weight loss in the parents. Anorexiant medications
      are not approved by the U.S. Food and Drug Administration for use in pediatric
      populations.

PMID- 10068711
TI  - Neurologic complications of systemic cancer.
AB  - Neurologic complications occur frequently in patients with cancer. After routine
      chemotherapy, these complications are the most common reason for hospitalization
      of these patients. Brain metastases are the most prevalent complication,
      affecting 20 to 40 percent of cancer patients and typically presenting as
      headache, altered mental status or focal weakness. Other common metastatic
      complications are epidural spinal cord compression and leptomeningeal metastases.
      Cord compression can be a medical emergency, and the rapid institution of high
      dose corticosteroid therapy, radiation therapy or surgical decompression is often
      necessary to preserve neurologic function. Leptomeningeal metastases should be
      suspected when a patient presents with neurologic dysfunction in more than one
      site. Metabolic encephalopathy is the common nonmetastatic cause of altered
      mental status in cancer patients. Cerebrovascular complications such as stroke or
      hemorrhage can occur in a variety of tumor-related conditions, including direct
      invasion, coagulation disorders, chemotherapy side effects and nonbacterial
      thrombotic endocarditis. Radiation therapy is the most commonly employed
      palliative measure for metastases. Chemotherapy or surgical removal of tumors is
      used in selected patients.

PMID- 10068712
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- 10068713
TI  - Esophageal atresia and tracheoesophageal fistula.
AB  - Esophageal atresia, with or without tracheoesophageal fistula, is a fairly common
      congenital disorder that family physicians should consider in the differential
      diagnosis of a neonate who develops feeding difficulties and respiratory distress
      in the first few days of life. Esophageal atresia is often associated with other
      congenital anomalies, most commonly cardiac abnormalities such as ventricular
      septal defect, patent ductus arteriosus or tetralogy of Fallot. Prompt
      recognition, appropriate clinical management to prevent aspiration, and swift
      referral to an appropriate tertiary care center have resulted in a significant
      improvement in the rates of morbidity and mortality in these infants over the
      past 50 years.

PMID- 10068714
TI  - Gout and hyperuricemia.
AB  - Gout is a condition characterized by the deposition of monosodium urate crystals
      in the joints or soft tissue. The four phases of gout include asymptomatic
      hyperuricemia, acute gouty arthritis, intercritical gout and chronic tophaceous
      gout. The peak incidence occurs in patients 30 to 50 years old, and the condition
      is much more common in men than in women. Patients with asymptomatic
      hyperuricemia do not require treatment, but efforts should be made to lower their
      urate levels by encouraging them to make changes in diet or lifestyle. Acute gout
      most commonly affects the first metatarsal joint of the foot, but other joints
      are also commonly involved. Definitive diagnosis requires joint aspiration with
      demonstration of birefringent crystals in the synovial fluid under a polarized
      light microscope. Treatment includes nonsteroidal anti-inflammatory drugs
      (NSAIDs), colchicine, corticosteroids and analgesics. In patients without
      complications, NSAID therapy is preferred.

PMID- 10068715
TI  - Recognizing problem sleepiness in your patients. National Center on Sleep
      Disorders Research Working Group.
AB  - Normal sleep is required for optimal functioning. Normal wakefulness should be
      effortless and free of unintended sleep episodes. Problem sleepiness is common
      and occurs when the quantity of sleep is inadequate because of primary sleep
      disorders, other medical conditions or lifestyle factors. Medications and
      substances that disturb sleep, such as caffeine and nicotine, or those that have
      sedating side effects, may also cause problem sleepiness. This condition can lead
      to impairment in attention, performance problems at work and school, and
      potentially dangerous situations when the patient is driving or undertaking other
      safety-sensitive tasks. However, problem sleepiness is generally correctable when
      it is recognized. Asking a patient and his or her bed partner about the
      likelihood of drowsiness or of falling asleep during specific activities, as well
      as questions that uncover factors contributing to the sleepiness, helps the
      physician to recognize the disorder. Accurate diagnosis of specific sleep
      disorders may require evaluation by a specialist. The primary care physician is
      in an ideal position to identify signs and symptoms of problem sleepiness and
      initiate appropriate care of the patient, including educating the patient about
      the dangers of functioning while impaired by sleepiness.

PMID- 10068716
TI  - Low-molecular-weight heparin in outpatient treatment of DVT.
AB  - Patients with a diagnosis of acute deep venous thrombosis have traditionally been
      hospitalized and treated with unfractionated heparin followed by oral
      anticoagulation therapy. Several clinical trials have shown that low-molecular
      weight heparin is at least as safe and effective as unfractionated heparin in the
      treatment of uncomplicated deep venous thrombosis. The use of low-molecular
      weight heparin in an outpatient program for the management of deep venous
      thrombosis provides a treatment alternative to hospitalization in selected
      patients. Use of low-molecular-weight heparin on an outpatient basis requires
      coordination of care, laboratory monitoring, and patient education and
      participation in treatment. Overlapping the initiation of warfarin permits long
      term anticoagulation. Advantages include a decreased incidence of heparin-induced
      thrombocytopenia and fewer episodes of bleeding complications. Future clinical
      trials evaluating the safety and efficacy of low-molecular-weight heparin in the
      treatment of complicated deep venous thrombosis will further define appropriate
      indications for use and strategies for outpatient management.

PMID- 10068717
TI  - Topical psoriasis therapy.
AB  - Psoriasis is a common dermatosis, affecting from 1 to 3 percent of the
      population. Until recently, the mainstays of topical therapy have been
      corticosteroids, tars, anthralins and keratolytics. Recently, however, vitamin D
      analogs, a new anthralin preparation and topical retinoids have expanded
      physicians' therapeutic armamentarium. These new topical therapies offer
      increased hope and convenience to the large patient population with psoriasis.

PMID- 10068718
TI  - NOF urges bone density tests for certain postmenopausal women and all women over
      age 65.

PMID- 10068719
TI  - NIH issues consensus statement on the rehabilitation of persons with traumatic
      brain injury.

PMID- 10068720
TI  - [Therapeutic endoscopy].

PMID- 10068721
TI  - [Therapeutic endoscopy in portal hypertension. When, how and how far in 1998].
AB  - Portal hypertension hemorrhage (PHH) due to esophageal varices (EV) rupture in
      nearly 80% of cases, or gastric varices (GV) in the remaining 20%, account for
      one-fifth of the GI tract bleedings in a general hospital. Its frequency, but
      more importantly, its magnitude, that causes up to one-third of the cirrhotic
      casualties, deserves constant update in its management. Diverse inherent patient
      factors influence the course of any PHH, i.e., a) remaining liver function, which
      is determinant; b) variceal size; c) sepsis, and d) alcohol intake. Mortality due
      to PHH is 27% during the first week, 41% within 6 weeks and 75% by one year of
      follow-up after the index hemorrhage. Time of intervention is then of utmost
      importance. All these key circumstances determine the ultimate course of the
      bleeding event, in many cases to a greater degree than the opportunity and
      quality of the specific treatment itself. This diversity of influential factors
      also jeopardizes adequate patient randomization in trials designed to compare
      treatment modalities. During the last decade, EV sclerosis, when compared to
      conventional medical treatment (non-beta blockers), has proved useful to stop
      active bleeding in 71 vs. 31% of cases, decreasing early and late recurrence from
      70 to 40%, and direct bleeding-related mortality from 24 to 9%, even when global
      mortality remains around 14% per year. Disappointing as it seems, remaining liver
      function is the determinant issue, but a biased underestimation factor may also
      play a role, due to greater surgical rescue of patients in the medical branch
      compared to EV sclerosis, 6 vs. 28%. Minor morbidity in 14% of sclerosis
      treatment has given way to endoscopic ligation with similar results and less
      morbidity. Prophylactic EV sclerosis was prohibited by prospective controlled
      trials, which demonstrated significant increase in bleeding and mortality, even
      though there might be a subgroup of patients with large varices or endoscopic
      prognostic signs of bleeding that decrease by 10% their incidence expected
      35%/year bleeding. GV bleeding remains a challenge; where cyanoacrylate may be
      needed to improve immediate control and prevent recurrence of PHH. These
      patients, as well as those failures to endoscopic treatment are candidates for
      intrahepatic portosystemic shunt (TIPS), although long-lasting control is
      achieved, in most cases, by liver transplant.

PMID- 10068722
TI  - [Esophageal prosthesis].
AB  - The patient with advanced esophageal cancer (AEC) is condemned to a short
      existence. The management of the majority of these patients is only palliative.
      The results obtained with surgery, radiotherapy and chemotherapy are only
      slightly encouraging. The patients require a highly effective palliative
      treatment that resolves the dysphagia, and the endoscopic procedures have
      demonstrated their high effectiveness. The principal objective is to better the
      quality of the life of the patient. Advantages of the Endoscopic Procedure (EP):
      this is carried out in only one session, does not require hospitalization, is low
      in cost, resolves the dysphagia, is well tolerated, the morbidity-mortality is
      low, and it is useful in esophagobronchial fistulas. Disadvantages: greater
      morbidity, is not useful in cervical esophagus, fluoroscopy is indispensable, it
      requires skill and experience, and the prosthesis can migrate. We report here on
      the insertion of 31 non-expandable polyvinyl EPs in patients with (AEC) (15.7% of
      197 cases of(AEC) diagnosed in 4 years 5 months); 21 males (67.74%) and 10
      females (32.25%); the average extension of the obstructed segment was 6.06 cm,
      and was localized in 77.41% in the inferior third; 64.51% were adenocarcinomas,
      and 32.25% were epidermoid carcinoma; five carcinomas (16.1%) originated in the
      Barrett esophagus; the complications were the following: migration 3 (9.67%),
      perforation 2 (6.45%), and obstruction by food 1 (3.22%). The dysphagia was
      resolved in all of the patients.

PMID- 10068723
TI  - [Endoscopic resection of the digestive tract mucosa].
AB  - The endoscopic resection of the mucosa of the digestive tract (ERM) is a set of
      techniques that have as their end the remotion of the mucosa for the diagnosis
      and treatment of localized diseases. The technique consists of the elevation of
      the mucosa with a submucosa injection of liquid or with suction in the interior
      of a transparent overtube. The procedure is indicated in the treatment of
      incipient malignant tumors of the esophagus, stomach, and colon, with a success
      rate that vacillates between 60 and 95%. An indispensable condition is the
      precise selection of patients through endoscopy and high-frequency endoscopic
      ultrasound. Other indications are the resection of flat and sessile polyps, the
      biopsies of submucosa tumors, and the taking of biopsies of great volume for the
      study of infiltrating and inflammatory neoplastic diseases. Based on the
      literature, principally descriptive and not comparative, the treatment of
      incipient digestive tract carcinomas with ERM has encountered serious
      difficulties in the Western world because of the rarity of the diagnosis, the
      scarce availability of endoscopic ultrasound, and lack of information of long
      term results. On the other hand, in the diagnostic field of mucosa diseases, and
      in the treatment of polyps, its utility is evident. In conclusion, ERM is added
      to the new endoscopic techniques for the obtaining of specimens of great volume
      and for the resection of sessile polyps. In the treatment of malignant tumors,
      ERM should be used with caution.

PMID- 10068724
TI  - [Treatment of non-variceal hemorrhage of the upper digestive tract].
AB  - High digestive tract hemorrhage (HDTH) represents on average 35% of the
      indications for endoscopy. It shows as a complication in different digestive
      pathologies or secondary to coagulopathies. Endoscopic management of non-variceal
      HDTH includes a gamut of procedures that when grouped together, have shown to be
      effective and safe in its control with an important diminishing in morbidity
      mortality, transfusion requirements, days of hospital stay, and the need for
      surgery. The most frequently employed methods are substance injections,
      multipolar coagulation, and thermic catheter, which achieve an average 90%
      hemostasis, but still inform high percentages of relapse. Approximately 25% of
      the patients with non-variceal hemorrhage may bleed again after endoscopic
      management. New procedures such as hemoclips and the combination of endoscopic
      methods have been used to diminish relapse. Endoscopic treatment should be
      carried out when we find bleeding lesions with Forrest Ia, Ib and IIa
      classifications, fundamentally because the risk of hemorrhagic relapse is very
      high among these groups. The treatment for the eradication of Helicobacter pylori
      in patients with bleeding peptic ulcers diminishes, in an important manner, the
      risk of the recurrence of hemorrhage.

PMID- 10068725
TI  - [Endoscopic gastrostomy].
AB  - Endoscopic gastrostomy is one procedure that is recommended for feeding or for
      gastric drainage, when the permanence of the feeding tube is required for a long
      time. This has arisen as a better alternative than surgical gastrostomy, because
      of its simplicity, efficiency, lower costs, and scarce morbidity-mortality. The
      most commonly recommended technique consists of gastric punction by percutaneous
      route and traction of the feeding tube from the mouth with the aid of an
      endoscopy. The indications are the necessity of feeding patients in a critical
      state who have gastric disorders and in whom prolonged gastric suction is
      required. It is contraindicated in morbid obesity, tension ascites, distension of
      intestinal loops, gastric carcinoma, pyloric obstruction, liver cirrhosis,
      previous gastric resective surgery, very voluminous hepatomegaly, and in patients
      who have had previous high abdominal surgery and who are suspected of having many
      loop adherences. The procedure may not be carried out when there exists the
      impossibility of passing the endoscope to the stomach. Complications occur is
      nearly 5% of the patients, and consist of wound infection due to the dragging of
      the oropharynx, periostomal leaks, peritonitis, gastrocolic fistulas, and
      pneumonia by aspiration. Mortality occurs in some 2%.

PMID- 10068726
TI  - [Endoscopic treatment of choledocholithiasis].
AB  - Since endoscopic access was possible to the choledochal conduit and to the
      intrahepatic bile ducts with the help of fluoroscopy, the ability of the
      endoscopist, his/her experience in technological development and in endoscopies
      as well as in the multiple accessories that allow us direct or indirect ingress
      to the bile ducts, choledocholithiasis has been able to be resolved with a
      success rate that oscillates between 95 and 99%, revolutionizing the management
      which formerly required from one to multiple surgical interventions with very
      high morbidity-mortality. Endoscopic management, with the passage of time, has
      shown itself to be the treatment of choice in choledocholithiasis as well as in
      other types of bile duct obstructive problems. The advent of new techniques of
      sphincterotomy, of the dilatation of the Oddi sphincter without the need for
      sphincterotomy, and also such as the diverse types of lithotripsy, including
      mechanical lithotripsy, electrohydraulic lithotripsy and extracorporeal
      lithotripsy, and the use of the laser for the destruction of the stones in the
      bile ducts, has increased the percentage of success in a significant way. This is
      of the utmost importance if we are to achieve working in a team with the surgeon,
      above all in the laparoscopic era in which we find ourselves, where the
      procedures are of minimum invasion, highly effective, come to resolve
      choledocholithiasis and chronic lithiasic cholecystitis with very low morbidity
      and mortality, and with a very short hospital stay.

PMID- 10068727
TI  - [Endoscopic drainage of the biliary system].
AB  - Endoscopic biliary drainage, with nasobiliary catheter or biliary prostheses,
      changed the treatment of biliary problems. The first indication for endoscopic
      drainage with biliary prostheses ware malignant diseases and then, benign
      diseases, and recently, the use of metallic autoexpandable prostheses in
      malignant and benign diseases to avoid stent occlusion. At the same time, the
      nasobiliary catheter for biliary drainage began to be used first in benign
      pathologies with good results and low morbidity-mortality. This article reviews
      the indications for biliary endoscopic drainage, with nasobiliary catheter or
      biliary prostheses, and the results for endoscopic management employing both
      treatments.

PMID- 10068728
TI  - [Endoscopic treatment of dyskinesia of the Oddi's sphincter].
AB  - Oddi sphincter dysfunction is manifested as a biliary- or pancreatic-type pain
      syndrome. At present, imaging studies are not very trustworthy for the diagnosis
      of this dysfunction, because of which direct endoscopic manometry offers the gold
      standard for confirming or ratifying the problem, supported by the Milwaukee
      Biliary Classification. Currently, the endoscopic approach has become the most
      effective alternative used for this type of diagnosis. Among the techniques may
      be found the following: endoscopic sphincterotomy, balloon dilation, the placing
      of biliary endoprostheses, and the injection of botulinic toxin in the Oddi
      sphincter. In our modest and short experience with six patients, of which five
      corresponded to group I of the Milwaukee bile classification, the above patients
      were treated successfully with sphincterotomy. The other two patients belonged to
      group type III of the Milwaukee classification, and were treated with botulinic
      toxin until the moment of a satisfactory response, for a period of 8 months.

PMID- 10068729
TI  - [Polypectomy of the digestive tract].
AB  - Endoscopic polypectomy was one of the first therapeutic procedures, as it was
      done even before the appearance of colonoscopy through rigid endoscopies.
      Immediately after the use of monopolar current in endoscopy, polyp resection in
      the digestive tract has been a elective treatment, and is reserved only for
      surgeries which are very extensive, or those which cannot be surrounded with a
      wire loop. The impact of the polypectomy in colonic adenomas has been notable
      because of the possibility of the diagnosis of the entire surgical piece, and for
      the treatment of lesions with premalignant potential. The success of the complete
      resection of a colonic polyp is directly proportional to its size and shape,
      given that pendicular polyps guarantee the complete extirpation of the tumor, in
      that sessile polyps require additional techniques to elevate the lesion. Among
      the precautions in prepolypectomy are found the following: Anti-inflammatory non
      steroidal (AINS) suspension; anticoagulant suspension, and adequate intestinal
      preparation. Hemorrhage and perforation occur in 0.1% of each. Postcoagulation
      syndrome is a secondary effect which only requires vigilance. The inherent
      complications in the use of secondary current are minimal when its technical
      principles are known. The success of endoscopic polypectomy depends on the
      refinement of the procedure, which is achieved through experience.

PMID- 10068730
TI  - [Comparison of 2 schedules based on pantoprazole for eradication of Helicobacter
      pylori in patients with active duodenal ulcer].
AB  - OBJECTIVE: To compare the efficacy and tolerability of a triple vs dual
      pantoprazole based therapy to eradicate Helicobacter pylori (H. pylori) in
      mexican patients with florid duodenal ulcer. BACKGROUND: The treatment of peptic
      ulcer disease was revolutionized by the fact that H. pylori generally induces
      chronic gastritis and peptic ulcer disease and that the cure of the infection
      prevents ulcer relapses. MATERIAL AND METHODS: 74 H. pylori positive patients
      with florid duodenal ulcer were randomized to receive either pantoprazole 40 mg
      bid in combination with clarithromycin 500 mg tid and amoxicillin 1 g bid (triple
      regimen PAC) or pantoprazole in combination with clarithromycin and placebo (dual
      regimen PC) during 14 days. To ensure complete ulcer healing all patients
      received an additional 2 weeks treatment with pantoprazole 40 mg od. 14C Urea
      Breath test (UBT) was the main criteria used to determine eradication rate with <
      150 disintegrations per minute (DPM) to consider a patient eradicated. In all
      patients culture, antibiotic susceptibility (E-test) and histology were
      performed. RESULTS: In the per protocol analysis (n = 66) the eradication rate
      was: PAC 93.5% vs PC 54.3% (p < 0.001). 76% of H. pylori strains were resistant
      to metronidazole. Tolerance and compliance were excellent in both groups.
      CONCLUSIONS: Triple therapy (PAC) was shown to be superior to dual therapy (PC)
      for H. pylori eradication in mexican patients with florid duodenal ulcer.

PMID- 10068731
TI  - [Comparative study of soft diet or clear liquids in the resumption of oral intake
      in the postoperative period].
AB  - BACKGROUND: The reinstitution of oral intake in patients who have undergone
      intraabdominal surgery has traditionally progressed in a stepwise fashion
      beginning with clear liquids, liquid diet and after an adequate tolerance regular
      diet. OBJECTIVE: To determine if the reinstitution of oral intake after major
      abdominal surgery with regular diet offers benefits into which it's not harmful
      for patients and reduce the in-hospital stay. TYPE OF STUDY: Prospective,
      randomized, open study conducted between October 1996 to May 1997. MATERIAL AND
      METHODS: Patients aged 18 and older submitted to elective or urgent surgery of
      the abdomen and pelvis were included with the exception of: bariatric surgery,
      esophageal resection, pyloroplasty, pancreato-duodenal resection, laparoscopic
      surgery and patients under ventilatory support or with enteral or parenteral
      nutrition. As soon as postoperative ileus disappeared patients were randomly
      assigned to receive regular diet (group 1) or clear liquids (group 2) as the
      first oral intake. Oral diet tolerance was evaluated as well as the caloric and
      protein intake, the in-hospital stay and the cost. RESULTS AND MEASUREMENTS:
      Group 1 was conformed by 63 patients, and group 2 for 69 patients. There was no
      difference between, sex, age, kind of surgery (elective or emergency) and the
      type of pathology. 96.6% of patients in group 1 tolerated regular diet and 96.9%
      of patients in group 2 tolerated clear liquids. Only two patients of each group
      required oral intake suspension. The in-hospital stay was 2.6 +/- 2.0 days in
      group 1 against 3.4 +/- 2.6 in group 2 (P = < 0.005), the cost of the in-hospital
      stay period after the beginning of oral intake was 2726 +/- 2107 pesos in group 1
      against 3547 +/- 2690 in group 2 (P = < 0.005), the caloric and protein intake
      were 1307 +/- 523 Kcals with 55.9 +/- 23.2 grams of proteins in group 1 and 651
      +/- 204 Kcals and 0 grams of proteins in group 2 (P = < 0.00001). CONCLUSIONS: No
      difference was found in adverse reactions with the use of regular diet as the
      first meal. The in-hospital stay and the cost were reduced significantly and the
      calories and grams of proteins are higher in group 1. These results suggest that
      the routine use of clear liquids as the initial postoperative diet may be
      unnecessary and nutritionally suboptimal when compared with regular diet.

PMID- 10068732
TI  - [Endoscopic retrograde cholangiopancreatography prior to laparoscopic
      cholecystectomy in patients with suspected choledocholithiasis].
AB  - BACKGROUND: Laparoscopic cholecystectomy is the treatment of choice for patients
      with symptomatic gallstones. The management of choledocholithiasis in these
      patients remains controversial. Endoscopic retrograde cholangiopancreatography
      (ERCP) with ductal stone clearance prior to laparoscopic cholecystectomy is one
      of the options. OBJECTIVE: To evaluate the results of ERCP prior to laparoscopic
      cholecystectomy in patients with suspected ductal stones. METHODS: We performed a
      retrospective study from patients who underwent ERCP prior to laparoscopic
      cholecystectomy in a four years period. RESULTS: ERCP was successful in 86 out of
      88 patients (97.7%). Common bile duct (CBD) stones were found in 34 patients
      (39.5%). Sixty two of 86 patients had symptomatic gallstones with abnormal liver
      function test and/or ultrasound. CBD stones were found in 25 of the 62
      symptomatic patients (40.3%). Twenty four patients had acute biliary
      pancreatitis. CBD stones were found in nine of these patients (37.5%). All
      patients with CBD stones underwent stone extraction after endoscopic
      sphincterotomy (ES). Sixteen other patients underwent ES for suspected
      obstruction at the ampulla. Stone extraction was successful in 100% of patients.
      There were six patients with complications (6.9%). Four patients had pancreatitis
      (4.6%), one patient hemorrhage (1.1%) and one patient cholangitis (1.1%).
      Analysis using logistic regression model showed that CBD stones on
      ultrasonography was the only variable significantly associated with
      choledocholithiasis (P < 0.001). CONCLUSIONS: Preoperative ERCP is useful in the
      management of CBD stones prior to laparoscopic cholecystectomy.

PMID- 10068733
TI  - [Neoplasms and dysplasias of the gallbladder and their relationship with
      lithiasis. A case-control clinicopathological study].
AB  - BACKGROUND: A strong association has been reported between gallbladder carcinoma,
      premalignant epithelial or metaplasic inflammatory lesions and cholelithiasis,
      varying the incidence among different ethnic groups. PURPOSE: To determine the
      frequency of association between such lesions and gallbladder lithiasis. MATERIAL
      AND METHODS: We examined histopathologic changes in 1,367 cholecystectomy
      specimens with (1,096) or without (271) lithiasis and established its frequency
      of association, correlating with main clinical data. RESULTS: Overall, 80% had
      lithiasis. In this group, pseudopyloric metaplasia (50%), intestinal metaplasia
      (16%), low grade dysplasia (40%), high grade dysplasia (16%), carcinoma in situ
      (1.5%) and invasive carcinoma (2.6%) were observed compared to 25%, 2%, 17%, 2%,
      0%, and 0% in the control group. The findings of 80% with lithiasis, 65% with
      carcinoma in situ and 90% of invasive carcinoma, all were in women. Median age of
      patients with low and high grade dysplasia, carcinoma in situ and invasive
      carcinoma was 42, 48, 53 and 61 years, respectively. CONCLUSIONS: Acute and
      xanthogranulomatous cholecystitis, adenomyomatosis, pseudopyloric and intestinal
      metaplasia, hyperplastic polyps, low and high grade dysplasia, tubular adenomas,
      carcinoma in situ and invasive carcinoma were more frequent when cholelithiasis
      was present (p < .05) than in cases without lithiasis.

PMID- 10068734
TI  - [Anorectal diseases in HIV-positive patients. A prospective study].
AB  - BACKGROUND: The acquired immunodeficiency syndrome (AIDS) has transformed in a
      illness pandemic and it is thought that 120 million of people will be infected by
      the year 2000. About thirty five percent of HIV positive patients will have
      rectal manifestations during their illness, and from these the most important
      anorectal manifestation are perianal sepsis, anal condyloma, hemorrhoidal
      disease, chronic diarrhea syndrome, anal ulcer and anorectal tumors. PURPOSE: To
      determinate in our medical environment which anorectal manifestation have the
      most frequency in HIV positive patients. PATIENTS AND METHOD: We developed a
      linear prospective, comparative and observational trial between December 1993 and
      December 1994, which included 83 patients distributed in 4 groups: 1) HIV
      homosexual patients with AIDS, 2) positive HIV homosexual patients without AIDS,
      3) negative HIV homosexual patients, 4) negative HIV heterosexual patients. The
      statistical analysis was done through a chi 2 (Chi square) test. RESULTS: In
      homosexual HIV patients with the disease, the most common lesion was the anal
      ulcer (55%). In positive HIV homosexual patients without disease and negative HIV
      homosexual patients the most frequent lesion is Condyloma acuminata (48 y 84%).
      In negative HIV heterosexual patients the most frequent disease was anal fistula
      (40%) and hemorrhoidal disease (36%). CONCLUSION: In negative HIV patients and
      positive HIV patients without disease the most frequent anorectal lesion is
      condyloma acuminata; when immunosuppression begins by AIDS, anal ulcer appears
      and is transformed in the most frequent anorectal disease in AIDS patients.

PMID- 10068735
TI  - [Why is the esophageal pH-metry required? Comparison with the recommendations of
      the American Association of Gastroenterology for its correct use].
AB  - INTRODUCTION: The esophageal pH monitoring is the most sensitive method to
      diagnose gastroesophageal reflux disease (GERD). However, there is a significant
      number of patients who do not require this test. Recently, guidelines for the
      appropriate use of pH monitoring have been published. AIM: To study the
      indications for the use of esophageal pH monitoring and to compare these
      indications with the guidelines published by the American Gastroenterological
      Association (AGA). METHODS: Seventy-five files of patients submitted to
      esophageal pH monitoring from February 1997 to July 1997 were reviewed. The
      clinical indications of this test were defined by history and endoscopic
      findings. These indications were compared with the AGA guidelines. RESULTS: In 50
      cases (67%) the indications for esophageal pH monitoring were performed according
      to AGA's guidelines, in 15 (20%) the indications of pH monitoring did not follow
      these guidelines and in ten cases (13%), the indication could not be determined.
      The most frequent indications were: 1) diagnosis of GERD in patients with a
      negative endoscopy; 2) detection of GERD in patients with extraesophageal
      manifestations; 3) refractory symptoms of GERD to proton pump inhibitors; 4)
      evaluation of GERD after antireflux surgery; and 5) assessment of non-cardiac
      chest pain. In 11 cases (15%), the indications for the use of pH monitoring was
      erroneous. CONCLUSIONS: In our motility laboratory, the majority of indications
      for esophageal pH monitoring were consistent with the AGA's guidelines. However,
      in 15% of the cases the pH monitoring was erroneously indicated.

PMID- 10068736
TI  - [Gastric neuroendocrine tumor].
AB  - Gastric carcinoid tumors arise from enterochromaffin-like (ECL) cells, these
      tumors represent 2-41% of all neuroendocrine tumors and 0.3% of malignant gastric
      neoplasias, being more common in men than in women, and commonly affecting people
      over 60 years old. These tumors arise from accelerated proliferation of the ECL
      cells as a consequence of the hypersecretion of gastrin, situation that can be
      present in atrophic gastritis and the Zollinger-Ellison syndrome. We report the
      case of a 51 year old hispanic female who presented with a 3 month history of
      abdominal pain, meteorism and constipation; she was treated with ranitidine and
      metoclopramide without clinical improvement, thus she underwent upper
      gastrointestinal endoscopy which showed an atrophic gastritis and gastric polyps.
      Histopathologic examination revealed a neuroendocrine gastric tumor which was
      positive to serotonine and gastrin stainings. Hormonal screening showed normal
      serum levels of LH, FSH, estradiol, ACTH, progesterone, calcitonin and cortisol.
      The serum level of gastrin was elevated with 500 pg/mL. Gammagraphic scanning
      with octreotide was negative for metastasis.

PMID- 10068737
TI  - [Doxycycline-induced esophageal ulcers].
AB  - Tetracycline is known as one of the antibiotics that induce esophageal ulcers.
      PURPOSE: Understand how these ulcers may behave and respond to treatment with
      sucralfate. METHOD: During the last two years we studied all patients complaining
      of dysphagia and odinophagia with an upper GI endoscopy, who were taking
      doxycycline in the last few days. All of them discontinued the drug once the
      diagnosis was done and most of them were treated also with sucralfate, 1 g tid.
      RESULTS: Eleven patients took doxycycline prescribed for: pelvic inflammatory
      disease, acne, urinary tract and pulmonary infections. Odinophagia was the most
      common symptom over the next few days of treatment with some risk factors
      previously documented, such as taking pills just before bedtime and with a small
      amount of water. The esophageal ulcers were multiple and located mainly in the
      middle esophageal third. Symptoms disappeared 3.7 days after the medication was
      stopped, while those taking sucralfate did not change the period of symptoms.
      CONCLUSIONS: Physicians must be aware of the doxycycline induced esophageal
      ulcers and discontinuation of the antibiotic as the main treatment, while
      sucralfate even though has shown to cover these ulcers, does not change the
      outcome. Therefore, they must encourage then patients to take the pills with
      enough liquid, in supine position and have special attention to the elderly and
      those with any kind of esophageal disease.

PMID- 10068738
TI  - [Metronidazole-induced esophageal ulcer. A case report].
AB  - A 25 years old female, previously in good health, complained of odinophagia and
      retrosternal pain. The last 3 days, she has been ingesting metronidazole 500 mg
      t.i.d. Last pill was swallowed the night before without liquids, at bed time.
      Esophagoscopy showed two ulcers in the middle portion of the esophagus. The
      patient stopped the medication, received liquid diet and sucralfate 2 g b.i.d.
      Clinically and endoscopically healing was achieved one week later. This case is
      important due to the high frequency of metronidazole prescription in Mexico.

PMID- 10068739
TI  - [Intramural esophageal abscess].

PMID- 10068740
TI  - [Choledochal cyst].

PMID- 10068741
TI  - [Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Editors of Medical Journals].

PMID- 10068742
TI  - [Utilization of medical resources for patients with irritable bowel syndrome in a
      tertiary hospital].
AB  - BACKGROUND: The irritable bowel syndrome (IBS) produces a high cost to society in
      terms of work loss, consultations, medical tests, treatments and even unnecessary
      surgeries. AIMS: To evaluate the use of medical resources by IBS patients in a
      tertiary hospital. METHODS: Retrospective study of medical records from patients
      with IBS younger than 60 years old. Number of clinical studies, consultations to
      all specialties and number of surgeries were analyzed. RESULTS: Between 1987 and
      1996, 98 patients age (mean) 40.8 years, were identified. Follow-up time was 33.4
      months (1-243), during a mean of 22.4 studies per patient (1-82) were solicited.
      Prior to IBS diagnosis, 5.0 studies per patient (I-II) were required. In 87% of
      the cases, IBS diagnosis was established during the first visit. Each patient
      consulted 3.6 times/year, 44.2% for gastrointestinal symptoms and 48.6% for non
      gastrointestinal symptoms. The consultations with the most demand were internal
      medicine (53.0%), gastroenterology (38.8%), proctology (31.6%), psychiatry
      (21.4%), gynecology (18.4%) and urology (13.3%). Surgical history was found in
      39%, 17.3% had appendectomy and 13.3% cholecystectomy, 1.02% and 2.04%
      respectively were done after IBS diagnosis. CONCLUSIONS: Although the
      availability of the Rome criteria for the diagnosis of IBS, these patients
      require an excessive quantity of studies to eliminate the possibility of organic
      disease, and excessive number of annual medical consultations as well. IBS
      patients also have a high rate of appendectomies and cholecystectomies.

PMID- 10068743
TI  - [Clinical superiority of pantoprazole over ranitidine in the treatment of reflux
      esophagitis grade II and III. A prospective, double-blind, double-placebo study.
      Mexican clinical experience. Mexican Pantoprazole Study Group].
AB  - OBJECTIVE: To compare and contrast the efficacy and tolerability of a proton pump
      inhibitor, pantoprazole, to that of an H2 antagonist, ranitidine, in the
      treatment of patients with mild to severe reflux esophagitis. BACKGROUND: Reflux
      esophagitis is a common illness affecting 5-10% of the world's population. Acid
      reflux plays a major role in the disease's genesis, as do esophageal and gastric
      motility disturbances. METHODS: 315 patients (intent to treat) with
      endoscopically confirmed reflux esophagitis (Savary-Miller (SM) stages II and
      III) were recruited to the study by 46 mexican investigators in nine centers.
      Patients received either pantoprazole 40 mg once daily or ranitidine 150 mg twice
      daily in this double blind, randomized, parallel group study. Patients not
      achieving complete endoscopic healing after four weeks of therapy received an
      additional four weeks of treatment. Drug tolerability was assessed by adverse
      event reporting during the study. RESULTS: After four weeks pantoprazole therapy,
      81% of patients with SM II and 67% of the patients with SM III were healed; in
      contrast ranitidine healed only 67 and 30% of the patients respectively, all
      results expressed on an per-protocol basis. After eight weeks therapy the healing
      rates for pantoprazole group increased to 94% and the ranitidine group to 74% (p
      = 0.001). The incidence of adverse events was less than 2% in both treatment
      groups, thus both therapies were found to be well tolerated. CONCLUSIONS:
      Pantoprazole is superior to ranitidine in the treatment of mild to severe reflux
      esophagitis and is equally well tolerated.

PMID- 10068744
TI  - [Laparoscopic cholecystectomy in children].
AB  - BACKGROUND: Laparoscopic cholecystectomy is the standard current treatment in
      adults with cholelithiasis, the experience in children has been reported
      recently. OBJECTIVE: To report the utility and results with this new technology
      in the pediatric age. METHODS: We found six children, 10 to 15 years old, with
      gallbladder lithiasic disease, all were operated with a modified laparoscopic
      cholecystectomy technique. RESULTS: The operation was performed without
      complications, the average surgical time was 90 minutes, and the recover, was
      short and successful. CONCLUSIONS: Laparoscopic cholecystectomy in children can
      be safe and effective.

PMID- 10068745
TI  - [Eradication of Helicobacter pylori in peptic ulcer and chronic gastritis. A
      randomized clinical trial].
AB  - BACKGROUND: The Helicobacter pylori (Hp) is found in patients with gastritis and
      peptic ulcer approximately in up to 80 percent. The eradication rates of 80 to 90
      percent are achievable with some regimens. AIMS: Evaluate two regimens for H
      pylori eradication in gastritis and peptic ulcer. METHODS: Patients more than 20
      years old with gastritis, gastric and duodenal ulcer disease and H pylori
      positive entered the study. We investigated prior history of peptic ulcer and
      hemorrhage, NSAID's use, smoking, alcoholism and epigastric pain. Endoscopy was
      performed before and at the end of the 8-12 weeks treatment, biopsies were taken
      from the antrum for Hp histological detection. Patients were randomly assigned to
      receive bismuth-metronidazole-tetracycline-ranitidine or bismuth-metronidazole
      amoxicillin-ranitidine during two weeks. STATISTICAL ANALYSIS: chi square and
      multivariate analysis. RESULTS: One hundred and eighteen patients were included
      in this study, 52% male and 48% female with mean age of 47 +/- 16 years. History
      of peptic ulcer and bleeding was present in 79% and 62% respectively. NSAID's,
      and tobacco use among all patients was 49%, and 30%. Epigastric pain, melena and
      hematemesis was present in 90%, 47% and 24% respectively. H pylori eradication
      treatment was successful in 70% in both regimens (pNS). Was no related to age,
      tobacco and alcohol for Hp eradication (pNS), and NSAID's use was inversely
      related to Hp eradication (p < 0.05). Persistent peptic ulcer was seen in 23%.
      CONCLUSIONS: Eradication treatment was successful in 70% (p NS). Peptic ulcer
      refractory in 23% of patients and NSAID's use was inversely related to Hp
      eradication (p 0.05).

PMID- 10068746
TI  - [A comparative study of 2 methods of preparation for colonoscopic procedure].
AB  - BACKGROUND: Although ingestion of polyethylene glycol solution has become the
      standard preparation for colonoscopy since 1980, there is investigation of new
      safe, comfortable and cheap methods. OBJECTIVE: We carried out a prospective
      study in order to compare the utility and tolerance related to the preparation of
      the colon for colonoscopy, using a dioctyl sodium sulfosuccinate enema (SD)
      versus our conventional preparation. METHOD: Group A was prepared the day
      previous to the study with liquid diet, oral laxative and application of an SD,
      prior to the endoscopy received another SD. Group B was prepared three days with
      liquid diet, the day previous to the colonoscopy they ingested oral laxative and
      used a water enema (W(e)), and they used another W(e) the day of the procedure.
      The patients' tolerance in each case was compared using a scale assigned as good,
      fair and poor. The cleaning obtained in the colon was also evaluated in a scale
      of good, regular and bad, considering three colon segments. RESULTS: Forty-four
      patients had been studied, 19 men and 25 women; each group with 22 patients. In
      group A: the preparation tolerance was good in 14 cases (63.6%), fair in seven
      (31.8%) and poor in one (4.5%); also, the obtained cleaning up to the cecum was
      good in nine cases (40.9%) and fair in 13 (59%). In group B: the tolerance was
      good in five cases (22.7%) fair in 12 (54.5%) and poor in five (22.7%); the
      obtained cleaning in this group up to the cecum was good in two cases (9%), fair
      in 19 (86.3%) and poor in one (4.5%). CONCLUSIONS: The SD preparation was better
      tolerated and more effective in order to achieve the cleaning of the colon than
      the conventional one.

PMID- 10068747
TI  - [Achalasia, alacrima without adrenal insufficiency with peripheral and autonomic
      neurological dysfunction (Allgrove's syndrome)].
AB  - OBJECTIVE: To present a patient with Allgrove's syndrome and peripheral and
      autonomic neurological dysfunction. This pathological entity has not been
      previously reported in national medical literature. BACKGROUND: Allgrove's
      syndrome is comprised of achalasia, alacrima and adrenal insufficiency. It is a
      rare disease. Some isolated cases have been informed in the literature. The most
      extensive series was published by Grant et al in 1993. In this study, 20 patients
      from various european countries were analyzed. METHOD: We describe a patient with
      diagnosis suggestive of Allgrove's syndrome and expose the results of a review of
      the medical literature concerning this syndrome. We emphasize in neurological
      dysfunction of these patients. Such abnormalities are not actually well defined
      in this syndrome. RESULTS: A twelve-year-old male patient was admitted to the
      hospital for dysphagia. A diagnosis of achalasia was performed with endoscopy and
      esophagogram and confirmed with esophageal manometry. Physical examination showed
      alacrima and neurological dysfunction. Stimulation of adrenal function with ACTH
      (Cortosin) was normal. Neurologic examination revealed: peripheral neuropathy,
      autonomic dysfunction; corticospinal, psychomotor and intellectual impairment.
      CONCLUSION: Allgrove's syndrome must be in mind in physicians who see children
      with achalasia. Nevertheless adrenal insufficiency is not always present in cases
      when diagnosis is performed. It may appear several years afterwards. Neurological
      dysfunction seems to be the most prominent feature.

PMID- 10068748
TI  - [Intestinal hemorrhage for 21 years in a case of blue nevus syndrome].
AB  - OBJECTIVE: To report a case of gastrointestinal bleeding due to a blue rubber
      bleb nevus syndrome undiagnosed for 21 years. CASE: A woman of 28 years of age
      suffered chronic gastrointestinal bleeding starting at seven years of age. During
      these 21 years she received various treatment with oral and parenteral iron and,
      in addition, four blood transfusions. We found her to be anemic with 7.8 g/dL of
      hemoglobin (HB), iron deficient and with skin lesions in tongue, right hand and
      lower extremities. A skin biopsy diagnosed the lesions as cavernous hemangiomas.
      Multiple intestinal hemangiomas seen by radiologic, endoscopic and colonoscopic
      studies, established the diagnosis. She was treated with oral iron; three months
      later she was asymptomatic and with higher levels of HB (9.1 g/dL). CONCLUSION:
      The rarity of the syndrome and the fact that, as far as we know, it is the first
      case reported in Mexico, probably led to a delay in its diagnosis and to
      potentially dangerous therapy in this patient in spite of the fact that the
      diagnosis was not difficult.

PMID- 10068749
TI  - [Laparoscopic treatment of severe acute pancreatitis. A case report].
AB  - OBJECTIVE: To report the laparoscopic treatment of a patient with severe
      pancreatitis. BACKGROUND: The efficiency and advantages of laparoscopic surgery
      in the management on acute abdominal diseases has been demonstrated. The
      laparoscopic approach has been reported in the diagnosis and treatment of several
      pancreatic diseases, including severe cases of pancreatitis and its
      complications. MATERIALS AND METHODS: A 70-years-old male patient with acute
      abdomen in which a diagnostic laparoscopy was performed finding acute
      cholecystitis and severe pancreatitis. Seven days later because a torpid course
      required a reintervention to perform laparoscopic necrosectomy. CONCLUSION: The
      laparoscopic treatment in severe pancreatitis is possible in selected cases and
      offers advantages over the traditional procedure. Prospective studies and
      protocols are necessary to validate the laparoscopic approach in the diagnosis
      and treatment of severe pancreatitis.

PMID- 10068750
TI  - [Ileoanal reservoir: new concepts and current results].
AB  - More than 1,800 ileoanal pouches have been performed at the Mayo Clinic since
      1981 and results have been satisfactory in more than 90% of the patients.
      However, we continue to search for alternatives to improve postoperative results
      and avoid the complications that currently occur in a minority of patients.
      During the last two years new concepts and surgical techniques for the
      construction of the ileoanal reservoir have been described. Herein we present
      those innovations and compare them to our current institutional practice.

PMID- 10068751
TI  - [Gastric diverticulum].

PMID- 10068752
TI  - [Crohn disease].

PMID- 10068753
TI  - [Opening address of the President of the Mexican Association of
      Gastroenterology].

PMID- 10068754
TI  - [Closing address of the President of the Mexican Association of
      Gastroenterology].

PMID- 10068755
TI  - [Homage to Dr. Alfredo Vicencio Tovar].

PMID- 10068756
TI  - [Homage to Dr. Hector Orozco Zepeda].

PMID- 10068757
TI  - [Spontaneous hemorrhage in liver neoplasms. Experience at an institution].
AB  - OBJECTIVE: Retrospective review of a single Institution experience with the
      management of hepatic neoplasms complicated with spontaneous bleeding. METHODS:
      In a 11 years period from 1980 to 1990 we reviewed the medical charts of patients
      treated at our Institution with the diagnosis of hepatic neoplasms complicated
      with sudden bleeding. We recorded demographic information, clinical
      manifestations, treatment and outcome. A review of the world literature was done.
      RESULTS: We found six patients with the diagnosis of liver tumors complicated
      with sudden bleeding. Five patients were female with a age range from 30 to 67
      years old. Four of them had an adenoma (three of them single and one multiple)
      and the fifth had a non-parasitic cyst. Seventy-five per cent of the patients
      with the diagnosis of adenoma had used in the past oral contraceptives for at
      least three years. The sixth patient was a male with a ruptured hepatocellular
      carcinoma. Three patients were admitted in shock. Successful transcatheter
      hepatic arterial embolization was performed in two patients; the third required
      operative hemostasis. Major hepatic resections were performed in three patients
      including a total hepatectomy and liver transplant. All patients recovered
      satisfactorily. CONCLUSIONS: The spontaneous rupture of benign and malignant
      tumors of the liver is not a common phenomenon, but is a serious complication.
      The experience of our Institution and the reports of literature favor CT scan and
      arteriogram as the most effective diagnostic methods in this group of patients,
      but arteriogram has the advantage of its therapeutic potential. The long term
      prognosis of this patients depends of their pathological diagnosis.

PMID- 10068758
TI  - [Infrared photocoagulation in the treatment of hemorrhoids].
AB  - PURPOSE: The aim of this study was to determine the efficacy of infrared
      photocoagulation in the treatment of grades I and II of hemorrhoidal disease.
      MATERIAL AND METHODS: 60 patients with hemorrhoidal disease grades I and II were
      included, each one with transanal bleeding as the only symptom, without any other
      ano-rectal pathology. They were 30 male and 30 female patients, with 39.9 years
      as median age. Each had 1 to 4 photocoagulation sessions, according to the
      results obtained in each one. TECHNIC: Each application was 1.5 seconds duration,
      once every two weeks, in diamond or rainbow shape; 1 to 4 sessions were required.
      Follow up was 24 months. RESULTS: Good results were obtained in 66.6% since the
      second application, and in 93.4% at the end of the study; 4 (6.6%) patients were
      failures and had to be operated on. CONCLUSION: Treatment of hemorrhoidal disease
      grades I and II with infrared photocoagulation is an excellent alternative; it is
      painless, suitable as an outpatient procedure and its cost is low.

PMID- 10068759
TI  - [Breath tests as a noninvasive diagnostic method in Helicobacter pylori
      infection].
AB  - There are several diagnostic methods for Helicobacter pylori infection, some of
      them need an endoscopic procedure and biopsy to be performed (invasive) like the
      rapid urease test, culture and histology. Recently non invasive, specific,
      sensible, easy to perform and patient's well accepted methods had been developed
      known as breath test, based on the hydrolysis of labelled urea by Helicobacter
      pylori urease enzyme, to release ammonia and bicarbonate. Labelled CO2 reaches
      the bloodstream and the lungs, from where can be collected into the breath for
      quantification. Labelled urea has to options: 13C stable, non-radioactive and 14C
      unstable, radioactive. Breath test with 13C is based on the atomic mass
      difference between 12C and 13C and it is necessary a mass spectrometer and 40
      minutes to perform it. Breath test with 14C has 1 uCi (one micro-curie) of
      radioactivity (1/300 of total radiation received in one year from the
      environment); the test takes 10 minutes and the samples are read in a beta
      counter. Both non-invasive tests had demonstrated sensitivity and specificity
      comparable to established "gold standards" for Helicobacter pylori infection
      diagnosis.

PMID- 10068760
TI  - [Presence of acinar pancreas in reflux esophagitis and Barrett's esophagus].
AB  - Pancreatic metaplasia in Barrett's esophagus was originally described by
      Krishnamurthy et al. They found that these focal clusters of cells resemble
      pancreatic acinar cells by immunohistochemistry and electron microscopy. Wang et
      al one year later, described these same cell clusters in normal and inflamed
      gastroesophageal junction. We studied 318 cases diagnosed as Barrett's esophagus
      (199 cases) and chronic esophagitis (119 cases) in the ABC Medical Center seen in
      1996 and the first four months of 1997, to look for pancreatic acinar metaplasia.
      We found 14 cases of Barrett's esophagus and 11 cases of chronic esophagitis with
      pancreatic acinar metaplasia. By immunohistochemistry and electron microscopy
      that these cell clusters are actually acinar pancreatic cells. Our results are in
      keeping with those found by Krishnamurthy and Wang that the clusters represent
      pancreatic acinar cells and may be found in Barrett's esophagus and in chronic
      esophagitis. The significance of these findings remain to be elucidated.

PMID- 10068761
TI  - [Precut sphincterotomy: efficacy and complications].
AB  - BACKGROUND: The use of precut sphincterotomy has been criticized as potentially
      unsafe. Despite this, a number of tertiary referral center have reported their
      successful use of this technique to increase the rate of common bile duct
      cannulation and therapeutic procedures. AIM: To evaluate precut papillotomy and
      correlate the complication rate. METHODS-PATIENTS AND RESULTS: We performed
      precut sphincterotomy in 120 patients in whom attempts at standard common bile
      duct cannulation and sphincterotomy were unsuccessful. Bile duct diameters were
      correlated to the complication rate. Cannulation of the common bile duct and
      endoscopic sphincterotomy was successful immediately after precut sphincterotomy
      in 103 patients (86%), and was successful in 12 of the 17 patients who underwent
      repeat ERCP, for a total cannulation and sphincterotomy rate of 96%. Eight
      patients (6.9%) experienced complications: six bleeding, and two retroduodenal
      perforation. There was no procedure-related mortality, and complications were
      managed medically except on patient with bleeding who required surgical
      intervention. CONCLUSIONS: Precut sphincterotomy was effective and safe in
      facilitating cannulation and sphincterotomy in patients in whom standard
      cannulation attempts failed. Excluding patients with small duct size may further
      reduce the complication rate.

PMID- 10068762
TI  - [Giant abdominal pseudocyst in patients with ventriculoperitoneal shunts].
AB  - OBJECTIVE: To analyze the etiology, clinical picture, diagnostic methods,
      surgical treatment and follow up of a series of six patients with large abdominal
      pseudocyst as a complication of ventriculo-peritoneal shunts for cerebrospinal
      fluid relief. DESIGN: Study of a series of cases. PATIENTS AND METHODS: We
      studied six patients from 1992 to 1995 with large abdominal pseudocyst; there
      were four women and two men, with range of age from nine to 19 years, and average
      of 15.9 years. Diagnosis was supported by clinical findings, ultrasound and
      computed tomographic scan. RESULTS: Meningeal tuberculosis was the cause of
      hydrocephalus, in five cases and neurocysticercosis in one. The most common
      symptoms were diffuse abdominal pain, nausea and vomiting. All of them presented
      with abdominal distention and a soft mass filled with liquid that occupied most
      of the abdominal cavity without evidence of shunt malfunction. All patients
      underwent surgical treatment for excision of the pseudocyst and relocation of the
      catheter of the shunt, without morbidity on mortality. In the follow up we have
      not experienced recurrence of the pseudocyst in any case. CONCLUSION: According
      to our experience, we propose that in a patient with a history of meningeal
      tuberculosis and ventriculo-peritoneal shunt that presents with an abdominal mass
      should be investigated for the occurrence of a pseudocyst. The ultrasound and
      tomographic scan are of great value for diagnosis. Surgical treatment through an
      open laparotomy is the best option for these patients. Morbidity and mortality
      are considered low, without evidence of recurrence.

PMID- 10068763
TI  - [Post-traumatic intrahepatic extraductal bile collection].
AB  - BACKGROUND: Intrahepatic extraductal biliary collections are a rare complication
      of abdominal trauma. OBJECTIVE: To describe two patients with diagnosis of
      posttraumatic intrahepatic extraductal biliary collections. CASE REPORT: Two male
      patients suffered multiple severe injuries, one of them from blunt trauma and the
      other from penetrating trauma; their main clinical manifestations were fever and
      jaundice. CT scan was the best suited diagnostic tool for evidencing the
      intrahepatic collections. Both patients underwent surgical drainage, only one of
      them had a satisfactory evolution. CONCLUSIONS: Posttraumatic intrahepatic
      extraductal biliary collections are a rare complication of abdominal trauma, its
      presence should be suspected in patients with hepatic trauma showing jaundice,
      fever and/or right upper quadrant pain between the second and sixth week
      following abdominal trauma.

PMID- 10068764
TI  - [Current concepts in the treatment of hemorrhoids].
AB  - Hemorrhoidal disease is a common problem that affects a large number of patients.
      Usually multiple remedies are used by those patients without medical advise and
      for several reasons consultation with a specialist is often delayed. The large
      prevalence of popular misconception adds to this and occasionally makes adequate
      treatment difficult. Herein we present a brief and useful review of current
      relevant concepts in the management of patients with hemorrhoidal disease.

PMID- 10068765
TI  - [Tamoxifen and hepatocarcinoma].

PMID- 10068766
TI  - [Leiomyosarcoma of the terminal ileum].

PMID- 10068767
TI  - [Peutz-Jeghers syndrome].

PMID- 10068768
TI  - Confocal-multilabeling, ultrasensitive TUNEL analysis of DNA breaks in individual
      cells.
AB  - OBJECTIVE: To visualize and localize fragmented DNA strands within apoptotic
      cells by means of fluorescence using TdT-mediated dUTP-biotin nick end labeling
      (TUNEL) techniques, laser scanning confocal microscopy (CLSM) and factor analysis
      of biomedical image sequences (FAMIS). STUDY DESIGN: For this experiment,
      lymphoid reverted cells were used as a model. Characteristic DNA breaks inside
      apoptotic cells were detected using TUNEL techniques by a reaction involving
      tetramethyl rhodamin isothyocyanate (TRITC). The DNA from cell nuclei was
      counterstained using chromomycin A3 (CA3). The tandem TRITC-CA3 in CLSM was
      applied to investigate the ability to detect DNA breaks in individual cells using
      TUNEL techniques and its amplified variants (TUNEL-CARD). FAMIS was applied on
      dynamic sequences of images of TUNEL preparations and on four-dimensional (4-D)
      sequences of images of TUNEL-CARD preparations. RESULTS: Distribution and
      amplitude of fluorescent structures were characterized on dynamic sequences of
      images. Characterization was improved when FAMIS was applied on 4-D sequences of
      images, taking into account differences in photobleaching and/or spectrum of
      TRITC and CA3. CONCLUSION: It is possible to discriminate targets from CA3. FAMIS
      and TUNEL methods can be used to visualize and localize multiple DNA breaks in
      lymphoid reverted cells in improved methods of experimentation.

PMID- 10068769
TI  - A method for simultaneous quantification of monoclonal antibody Ki-67 and DNA
      content by flow cytometry. Application to breast carcinomas.
AB  - OBJECTIVE: To seek a method assessing Ki-67 immunostaining and DNA content by
      flow cytometry simultaneously. STUDY DESIGN: The murine monoclonal antibody Ki-67
      (Ki) identifies a nuclear protein complex expressed by all nonquiescent tumor
      cells. Since the antigen detected by Ki is quite labile in most fixation and
      embedding protocols, a new method for simultaneous quantification of nuclear Ki
      immunofluorescence and DNA content by flow cytometry was developed. Unfixed,
      solid tumor cells are permeabilized only with saponin to preserve Ki antigen. The
      percentage of Ki-positive cell subpopulations calculated by subtraction of the
      related aspecific fixation histogram gives optimal results more rapidly than by
      cytogram analysis. Application to breast carcinoma shows the feasibility of the
      method. RESULTS: Significant correlations between Ki staining and the S-phase
      fraction were observed. Mean Ki labelling rates of aneuploid tumors were
      significantly higher than those of the diploid tumors, and significant
      differences between histologic types were found. CONCLUSION: This technique can
      be considered a fast, sensitive and optimal method to evaluate the proliferative
      activity of breast carcinomas and possibly of other solid tumors in a department
      of pathology.

PMID- 10068770
TI  - Cytologic grading and DNA image cytometry of breast carcinoma on fine needle
      aspiration cytology smears.
AB  - OBJECTIVE: To correlate the cytologic grade of breast carcinoma with DNA image
      cytometry (ICM) and nuclear area on fine needle aspiration cytology (FNAC)
      smears. STUDY DESIGN: In this prospective study, FNAC material from 28 breast
      carcinomas were studied for cytologic grade and DNA ICM. Breast carcinomas were
      classified as grade 1-3 (low to high). DNA histograms were classified by the
      modified Auer method. Degree of hyperploidy (DH), ploidy balance (PB) and nuclear
      area (NA) were measured on Feulgen-stained smears by a CAS 200 image cytometer.
      Cytologic grade was correlated with DNA ICM findings and NA. RESULTS: There were
      3 cytologic grade 1, 13 grade 2 and 12 grade 3 breast carcinomas. Seven of eight
      cases of hypertetraploid aneuploidy were grade 3 tumors. All cytologic grade 1
      tumors were diploid. There were significant differences in DH, PB and NA in
      different grades of breast carcinoma (one-way ANOVA). CONCLUSION: DNA image
      cytometry in combination with cytologic grading might offer additional
      information for the characterization of breast carcinomas diagnosed by FNAC.
      These observations are of particular interest with the introduction of
      preoperative chemotherapy.

PMID- 10068771
TI  - Measurement variability and diagnostic sensitivity of gastric mucosal
      inflammatory cell morphometry.
AB  - OBJECTIVE: To assess the variability and sensitivity of morphometric measures of
      gastric mucosal lymphocyte and plasma cells to determine a systematic procedure
      for evaluating the density of these mononuclear inflammatory cells (MNC). STUDY
      DESIGN: Gastric biopsies of antrum (n = 3), incisura angularis (n = 2) and corpus
      (n = 3) from two controls and three patients with Helicobacter pylori-related
      gastritis (antral, diffuse or multifocal gastritis) were considered. In each
      biopsy, three fields from each of three sections were selected. In each field,
      stromal area was obtained by subtracting gland area (GA) from total area, and MNC
      were counted. Results were expressed as MNC/total mm2 and MNC/stromal mm2.
      Correlations with GA, coefficients of variation (CV), discriminant power analysis
      and analysis of variance were performed. RESULTS: Correlations always existed
      between GA and MNC/total mm2 and rarely between GA and MNC/stromal mm2. CV of
      MNC/stromal mm2 were lower (18%) than those of MNC/total mm2 (30%). High
      sensitivity (95.4%) and specificity (95.8%) were found for MNC/stromal mm2 but
      not for MNC/total mm2. Differences in MNC/stromal mm2 existed in all subjects (P
      < .0001). Highly significant differences in MNC/stromal mm2 were also found
      between normal and inflammatory states, gastric sites and sections. CONCLUSION:
      In contrast to MNC/total mm2, MNC/stromal mm2 is an unbiased estimate of MNC
      density. The following sampling procedure is proposed: two biopsies from each
      gastric site, two sections from each biopsy and two microscopic fields from each
      section.

PMID- 10068772
TI  - DNA ploidy in seminal vesicle cells. A potential diagnostic pitfall in urine
      cytology.
AB  - OBJECTIVE: To verify that abnormal DNA ploidy in urine cytology can occasionally
      be attributed to contamination by seminal vesicle cells. STUDY DESIGN: In the
      first part of this study, we analyzed the DNA content of six urine cytology
      specimens containing seminal vesicle cells. In the second part, we evaluated 21
      Feulgen-stained prostate core biopsies containing seminal vesicle-type epithelium
      using a CAS-200 system. DNA index, proliferative activity (S + G2M) and degree of
      hyperploidy (> 5C) were determined in each case. RESULTS: All six urine cytology
      specimens were diploid, with all but one containing hyperploid cells (range, 0
      16%; mean, 6.3%). Seminal vesicle cells from prostate biopsies showed a broad
      range of ploidy abnormalities. Ten cases (48%) showed an aneuploid peak, two
      cases (9%) showed a tetraploid peak, and nine cases (43%) showed only a diploid
      peak. All but one case showed both an elevation in proliferative activity (mean S
      + G2M, 24.2%) and some hyperploid cells (mean, > 5C; 4.5%). CONCLUSION: Seminal
      vesicle cells, although rarely seen in urine cytology, can cause abnormal DNA
      ploidy measurements. Morphologic criteria remain vital to an accurate cytologic
      diagnosis.

PMID- 10068773
TI  - Expert consultation for cervical carcinoma smears. Reliability of selected-field
      videomicroscopy.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of videomicroscopy image selection
      for expert consultation in cervical cytology. STUDY DESIGN: One hundred
      diagnostically difficult cervical cytologic smears were selected and rescreened
      by a general pathologist who chose, from each slide, four or five fields
      featuring abnormal cells. Video images were digitized and stored on a 512 x 512
      pixel matrix using an image acquisition and transmission system. Five experts
      each reviewed 20 of the 100 cases, and a sixth reviewed all 100 cases. Diagnoses
      based on selected digitized images were compared to those based on conventional
      examination of whole slides. RESULTS: Intraobserver agreement was fair to
      excellent for all six experts (kappa value: 0.47-0.81); it was complete or
      acceptable in 68.4-85% of cases. Compared to the reference diagnosis,
      interobserver agreement was not significantly different whether cases were
      examined by screening the entire slide or by videomicroscopy of selected fields.
      The marked discordance in four cases concerned very small cells the significance
      of which was misinterpreted on videomicroscopy because of poor image quality due
      to lack of focus setting. CONCLUSION: This exploratory study showed that
      selection of videomicroscopy images seems as reliable as conventional examination
      of slides for expert consultation on diagnostically difficult cervical cytologic
      smear cases.

PMID- 10068774
TI  - Ki-67 immunostaining and stereologic estimation of nuclear volume in melanocytic
      skin tumors.
AB  - OBJECTIVE: To investigate the proliferative activity and mean nuclear volume
      (MNV) of melanocytic skin tumors. STUDY DESIGN: Proliferative activity, assessed
      by immunostaining for the Ki-67 monoclonal antibody (reactive with all actively
      cycling cells), and MNV, estimated by means of a stereologic method, were
      determined in 60 cutaneous melanocytic tumors, including 28 primary malignant
      melanomas (PMM), 13 compound nevi (CN), 11 dysplastic nevi and 8 metastatic
      malignant melanomas. RESULTS: Both MNV and Ki-67 expression differed
      significantly between CN and other melanocytic tumors and showed a good
      correlation with Clark's level (a well-established prognostic parameter in PMM).
      CONCLUSION: The association of proliferative activity and quantitative nuclear
      features may be helpful in the interpretation of the degree of malignancy in
      melanocytic skin tumors.

PMID- 10068775
TI  - Digital image analysis of silver-stained nucleolar organizer region--associated
      proteins in endometrial cytologic samples.
AB  - OBJECTIVE: Digital image analysis was applied to determine the number, area and
      size of silver-stained nucleolar organizer regions (AgNORs) in cytologic samples
      from curettage in normal, hyperplastic and malignant endometrium. STUDY DESIGN:
      Thirty-two archival cytologic smears from curettage (previously stained by the
      Papanicolaou method) with the histologic diagnosis (4 inactive endometrium, 5
      secretion, 5 proliferation, 5 simple hyperplasia, 5 complex hyperplasia, 3
      atypical hyperplasia, 5 adenocarcinoma, grade 1) were analyzed with the AgNOR
      technique. Count, area and size of AgNORs were analyzed in 50 cells per sample
      using a magnification of 1,000x. Quantitative analysis was performed on an SFORM
      digital imaging system. Data were analyzed with the SPSS/PC+ program. Mann
      Whitney and chi 2 tests were performed. RESULTS: The average value of AgNOR count
      increased from normal to hyperplastic endometrium and well-differentiated
      adenocarcinoma. Differences were significant except between atypical hyperplasia
      and adenocarcinoma. Four, five and more AgNORs in 40% or more of the nuclei were
      found in complex and atypical hyperplasia and adenocarcinoma. Proliferation, and
      simple and atypical hyperplasia had similar mean values of AgNOR area. The mean
      total AgNOR area value increased from normal to hyperplastic had similar mean
      values of AgNOR area. The mean total AgNOR area value increased from normal to
      hyperplastic and well-differentiated adenocarcinoma. Differences were
      statistically significant. AgNOR size in well-differentiated adenocarcinoma was
      significantly different from that in normal endometrium and different grades of
      hyperplasia. CONCLUSION: Digital image analysis of AgNOR count, area and size
      enabled a distinction to be made between normal, hyperplastic and malignant
      endometrium.

PMID- 10068776
TI  - Laser scanning analysis of cell-cell communication in cultured human prostate
      tumor cells.
AB  - OBJECTIVE: To investigate gap-junctional intercellular communication (GJIC) in
      LNCaP and DU145 human prostate cancer cells. STUDY DESIGN: Normal rat liver F344
      (WB1) cells were used as positive controls. Functional GJIC was inspected using
      either the scrape-loading/dye transfer (SL/DT) method or fluorescence recovery
      after photobleaching (FRAP) analysis. In the former, GJIC activity was expressed
      as a measure of the extent of diffusion of Lucifer Yellow after cell monolayers
      were scraped using a surgical blade and exposed to dye for a few minutes at room
      temperature. In the latter, cells were incubated for 15 minutes at 37 degrees C
      with 5,6-carboxyfluorescein diacetate dye and the dye transfer visualized by
      photobleaching individual cells with a 488-nm laser and monitoring the recovery
      of fluorescence using a laser cytometer. RESULTS: The preliminary results
      obtained indicate that neither LNCaP nor DU145 cells have functional GJIC, while,
      as expected, WB1 cells show unimpaired GJIC activity. Equivalent results were
      consistently obtained using either SL/DT or the FRAP approach. However, using
      FRAP analysis, DU145 cells only showed weak recovery of fluorescence after a
      total observation interval of 15 minutes. CONCLUSION: The present data, though
      preliminary, suggest that disruption of GJIC may play a role in development of
      malignancy in the human prostate.

PMID- 10068777
TI  - Quantitative image analysis of estrogen and progesterone receptors as a
      prognostic tool for selecting breast cancer patients for therapy.
AB  - OBJECTIVE: To assess estrogen and progesterone receptor presence in human breast
      tumors using immunocytochemical analysis. STUDY DESIGN: For both estrogen (ER)
      and progesterone (PR) receptor assay, percent of stained cells and intensity of
      staining were estimated on a series of 251 consecutive breast cancer cases from
      the M. Ascoli Cancer Hospital Center in Palermo using the CAS 200 image analysis
      system. RESULTS: Cytochemical assay revealed a differential distribution of both
      ER and PR, by menopausal status of the patients; premenopause (PreM) was mostly
      ER negative (63%), and postmenopause (PostM) > 10 years was mostly ER and PR
      positive (64%). The percent of cells stained for ER was significantly different
      between PreM and PostM patients when they were considered as a whole. By
      contrast, no difference emerged for PR staining among menopausal groups. Overall,
      patients whose tumors were PR positive showed a significantly (P < .03) longer
      interval free of relapse. CONCLUSION: The present results suggest that PRs behave
      as better indicators than ERs of early relapse in breast cancer patients. Further
      studies, with longer follow-up, are needed, however, to validate this concept.

PMID- 10068778
TI  - Nodular hyperplasia of the prostate. Quantitative evaluation of secretory cell
      changes after treatment with finasteride.
AB  - OBJECTIVE: To quantitatively evaluate the changes in the secretory cells in
      nodular hyperplasia of the prostate after treatment with finasteride. STUDY
      DESIGN: Secretory cell nuclear and nucleolar measurements were performed with an
      image analyzer in hematoxylin-and-eosin-stained sections of 20 untreated and 20
      finasteride-treated cases of nodular hyperplasia. An immunoperoxidase method was
      used to stain the secretory cells with a monoclonal antibody-directed, anti
      prostate specific antigen (PSA). The size of prostates was determined by
      transrectal ultrasound. For both groups the serum PSA values were determined.
      RESULTS: After six months of treatment with finasteride, the prostates shrank by
      approximately 20% with the therapeutic regimen (as determined by transrectal
      ultrasound), whereas the serum PSA values decreased by 30% (before therapy, <
      4.00 ng/mL). The secretory cells appeared smaller than those from the untreated
      group of patients, and the cytoplasm staining of the PSA marker was slightly
      diminished. Karyometric analyses showed that the nuclear and nucleolar size were
      smaller in comparison with the controls. In particular, the mean nuclear and
      nucleolar area in the treated group were, respectively, 34.12 and 1.424 micron 2,
      whereas in the untreated group the values were 40.46 and 2.261. CONCLUSION:
      Reduced androgen stimulation after treatment with finasteride induces involution
      of secretory cells. This may be responsible for the decrease in the serum PSA
      level and may contribute to the reduction in prostate size.

PMID- 10068779
TI  - Cell growth and death in malignant lymphomas. A quantitative analysis.
AB  - OBJECTIVE: To review the value of biopathologic factors in single lymphomatous
      patients across the boundaries of histologic classification. STUDY DESIGN: In a
      series of previous studies, based on a large collection of biopsy samples, the
      value of the above biopathologic characteristics in individual lymphomatous
      patients was quantitatively evaluated. RESULTS: The relationships between
      apoptotic index and growth fraction, in light of the expression of oncogenes,
      which regulate cell birth and death, were of particular value in determining the
      growth pattern of different lymphoma cases across the boundaries of histologic
      classification. CONCLUSION: The study of mechanisms that regulate cell
      proliferation and death might have therapeutic implications as the proper
      therapeutic approach should be based on detailed knowledge of the kinetic and
      molecular characteristics of each tumor.

PMID- 10068780
TI  - Quantitative histochemical study of hyaluronic acid binding protein and the
      activity of uridine diphosphoglucose dehydrogenase in the synovium of patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To examine hyaluronic acid (HA) dynamics in synovia with rheumatoid
      arthritis (RA), relying on a new quantitative technique introduced into
      histochemistry. STUDY DESIGN: Synovial lesions from 28 patients were classified
      into four histologic stages of RA according to the degree of inflammation. The
      distribution of HA was histochemically investigated with a hyaluronic acid
      binding protein (HABP) and that of HA-producing cells enzyme histochemically with
      the expression of uridine diphosphoglucose dehydrogenase (UDPGD) activity in the
      synovium of RA patients. The results were quantified using an image processor for
      analytical pathology. The positive area of HABP reaction, the number of UDPGD
      positive cells and the color density of the enzyme-histochemistry of UDPGD
      activity were measured with the IPAP system. RESULTS: HA was shown to be
      diffusely distributed in the synovia, particularly densely in the superficial
      layer, and the distribution overlapped with that of UDPGD activation. HA
      distribution and UDPGD activity varied with the severity of synovial
      inflammation, and the positive area was the most extensive in the early stage,
      while it completely disappeared in the fibrotic stage. CONCLUSION: We assume that
      for HA, not only does the production decrease, but the range of distribution
      contracts with time.

PMID- 10068781
TI  - Constructing a local district telepathology network in Japan. Diagnosis of
      intraoperative frozen sections via telepathology over an integrated service
      digital network and the National Television Standard Committee System.
AB  - OBJECTIVE: To construct a local telepathology network between the Department of
      Pathology, Tohoku University Hospital, and Koritu Kesennuma Hospital, about 150
      km away. STUDY DESIGN: Tohoku University Hospital is connected with Koritu
      Kesennuma Hospital by an integrated service digital network for telepathology
      using the National Television Standard Committee system. The cases submitted for
      telepathology were limited to those in which a rapid intraoperative diagnosis was
      made on frozen sections. RESULTS: At this writing, more than 200 cases were
      diagnosed during a period of 2.5 years. The cases submitted increased with time,
      amounting to 150 in 1996. In some cases the use of telepathology proved to be
      fairly advantageous. For example, in one case a radical operation was avoided
      because of a diagnosis on intraoperative frozen sections. DISCUSSION: There are
      problems to be solved before telepathology becomes available for practical use:
      (1) misdiagnosis due to poor quality of instruments, including the transmission
      cable and pictures; (2) cost-benefit ratio, (3) protection of patients' privacy,
      and (4) overwork for pathologists. The Japanese government will officially accept
      telepathology as a means of medical examination in the future. Despite some
      problems left, telepathology is a promising technology.

PMID- 10068782
TI  - DNA ploidy, Ki-67 and p53 as indicators of lymph node metastasis in early gastric
      carcinoma.
AB  - OBJECTIVE: To perform flow cytometric and immunohistochemical analysis of early
      gastric carcinoma in order to investigate the clinical value of DNA ploidy, Ki-67
      and p53 as indicators of lymph node metastasis. STUDY DESIGN: We studied 108
      cases of surgically resected early gastric carcinoma, which comprised 21 cases
      showing positive lymph node metastasis (group A) and 87 cases showing negative
      lymph node metastasis (group B). RESULTS: Aneuploidy was seen in 16 cases (76.2%)
      in group A in contrast to 10 cases (11.5%) in group B (P = .0029). The mean value
      of the Ki-67 labeling rate in all cases was 21.9%, and 15 cases (79.0%) showed a
      Ki-67 labeling rate of more than 21.9% in group A, while they numbered 31 (37.4%)
      in group B (P = .0016). Cases with cell positive for p53 protein numbered 15
      (75%) in group A, while they numbered 38 (46%) in group B (P = .0460).
      CONCLUSION: DNA aneuploidy, a high labeling rate of Ki-67 and overexpression of
      p53 are all useful indicators of lymph node metastasis in patients with early
      gastric carcinoma.

PMID- 10068783
TI  - Stereologic estimates of glomerular volume in unilaterally nephrectomized rats.
AB  - OBJECTIVE: To quantitatively evaluate the changes in glomeruli in unilaterally
      nephrectomized adult rats by unbiased stereologic techniques. STUDY DESIGN: Adult
      rats received unilateral nephrectomy (UN) or a sham operation. Four weeks later
      the remnant kidneys were fixed and sampled by the fractionator method.
      Consecutive sections were prepared and stained. Morphometric analyses were
      performed by a light microscope equipped with computer-assisted digitizer.
      RESULTS: The total glomerular volume increased by 51% (P < .01). The volume
      density of glomeruli did not change (5.58 +/- 0.22 x 10(-2) vs. 5.51 +/- 0.44 x
      10(-2), P > .50). In contrast, the numerical densities of glomeruli decreased by
      36% (P < .05). CONCLUSION: Glomerular enlargement, but not the increase in
      glomerular number contributed heavily to compensatory glomerular growth after UN
      in rats.

PMID- 10068784
TI  - Rhodococcal systematics: problems and developments.
AB  - Various approaches that have been used in the development of a system of
      classification for the genus Rhodococcus are discussed. The application of
      chemotaxonomic, molecular systematic and numerical phenetic methods have greatly
      contributed to improvements in the systematics of rhodococci and related mycolic
      acid containing actinomycetes. The genus currently encompasses twelve validly
      described species but improved diagnostic methods are needed to distinguish
      between them. In addition, evidence from 16S ribosomal RNA sequencing suggests
      that the genus is still heterogeneous.

PMID- 10068785
TI  - Diversity of isolates of Rhodococcus equi from Australian thoroughbred horse
      farms.
AB  - Pulsed field gel electrophoresis of restriction endonuclease digested genomic DNA
      from a collection of clinical isolates of Rhodococcus equi was used to compare
      strain diversity on different Thoroughbred horse farms over time. Restricted
      diversity was found among the isolates tested, as the same strains were detected
      on multiple farms and in multiple years. Marked variation occurred in strain
      prevalence with some strains being represented by single isolates, and the most
      prevalent by 26 isolates. There were dominant strains on some farms and the
      prevalence of some strains differed between farms. Infection with multiple
      strains was noted in some cases where multiple isolates from a single foal were
      examined.

PMID- 10068786
TI  - Novel rhodococci and other mycolate actinomycetes from the deep sea.
AB  - A large number of mycolate actinomycetes have been recovered from deep-sea
      sediments in the NW Pacific Ocean using selective isolation methods. The isolates
      were putatively assigned to the genus Rhodococcus on the basis of colony
      characteristics and mycolic acid profiles. The diversity among these isolates and
      their relationship to type strains of Rhodococcus and other mycolate taxa were
      assessed by Curie point pyrolysis mass spectrometry (PyMS). Three major (A, C, D)
      and two minor (B, E) groups were defined by PyMS. Cluster A was a large group of
      isolates recovered from sediment in the Izu Bonin Trench (2679 m); Cluster C
      comprised isolates from both the Izu Bonin Trench (6390 and 6499 m) and from the
      Japan Trench (4418, 6048 and 6455 m). These Cluster C isolates showed close
      similarity to Dietzia maris and this was subsequently confirmed using molecular
      methods. Cluster D contained isolates recovered from a sediment taken from a
      depth of 1168 m in Sagami Bay and were identified as members of the terrestrial
      species Rhodococcus luteus. Clusters B and E had close affinities with members of
      the genera Gordonia and Mycobacterium. The presence of Thermoactinomyces in
      certain of the deep-sea sediments studied was indicative of the movement of
      terrestrial material into the ocean depths. 16S ribosomal RNA gene sequence
      analyses produced excellent definition of most genera of the mycolata, and
      indicated that the among the deep sea isolates (1) were novel species of
      Corynebacterium, Gordonia and Mycobacterium, and (2) a Sea of Japan isolate the
      phylogenetic depth of which suggests the possibility of a new genus. Polyphasic
      taxonomic analysis revealed considerable diversity among the deep sea rhodococci
      and evidence for recently diverged species or DNA groups.

PMID- 10068787
TI  - In situ detection of rhodococci associated with activated sludge foams.
AB  - Genus-specific 16S rRNA targeted oligonucleotide probes, Rco1 and Rco2, were
      designed and used to detect rhodococci in activated sludge foam samples by
      confocal laser scanning microscopy. Pure cultures were used to find the optimal
      hybridisation conditions which were determined by comparing the mean fluorescent
      intensities of target and non-target cells from images captured using a confocal
      laser scanning microscope (CLSM). The combination of fluorescent in situ
      hybridisation with rRNA-targeted oligonucleotide probes and confocal laser
      scanning microscopy provides an effective way of detecting rhodococci in
      environmental samples.

PMID- 10068788
TI  - Cell envelope composition and organisation in the genus Rhodococcus.
AB  - A knowledge of the organisation of the rhodococcal cell envelope is of
      fundamental importance if the environmental and biotechnological significance of
      these bacteria are to be understood and successfully exploited. The genus
      Rhodococcus belongs to a distinctive suprageneric taxon, the mycolata, which
      includes among others the genera Corynebacterium, Mycobacterium and Nocardia.
      Members of this taxon exhibit an unusual complexity in their cell envelope
      composition and organisation compared to other Gram-positive bacteria. Models
      that describe the architecture of the mycobacterial cell envelope are
      extrapolated here to provide a model of the rhodococcal cell envelope. The
      rhodococcal cell envelope is dominated by the presence of an arabinogalactan cell
      wall polysaccharide and large 2-alkyl 3-hydroxy branched-chain fatty acids, the
      mycolic acids, which are covalently assembled into a peptidoglycan
      arabinogalactan-mycolic acid matrix. This review further emphasises that the
      mycolic acids in this complex form the basis of an outer lipid permeability
      barrier. The localisation and roles of other cell envelope components, notably
      complex free lipids, lipoglycans, proteins and lipoproteins are also considered.

PMID- 10068789
TI  - Surface-active lipids in rhodococci.
AB  - Like other hydrocarbon-oxidising bacteria, rhodococci respond to the presence of
      alkanes by producing biosurfactant molecules to improve their ability to utilise
      these hydrophobic compounds as growth substrates. In the rhodococci these
      surfactants are predominantly glycolipids, the majority of which remain cell
      bound during unrestricted growth. Most work has been done on the trehalose
      mycolates formed by Rhodococcus erythropolis, but nitrogen-limited conditions
      lead to the production of anionic trehalose tetraesters also. As surfactants,
      these compounds, whether purified or in crude form, are able to reduce the
      surface tension of water from 72 mN m-1 to a low of 26, thus making them among
      the most potent biosurfactants known. They are also able to reduce the
      interfacial tension between water and a hydrophobic phase (e.g. n-hexadecane)
      from 43 mN m-1 to values less than one (Table 1). Biosurfactants have about a ten
      to 40-fold lower critical micelle concentration than synthetic surfactants. Such
      properties suggest a range of industrial applications, where a variety of surface
      active characteristics are appropriate. Interest in biosurfactants as industrial
      chemicals results from the toxicity of many petrochemical-derived surfactants.
      Currently world-wide surfactant production is on a very large scale, and the
      demand for them is increasing. However, the drive towards less environmentally
      damaging chemicals makes biosurfactants attractive as they have lower toxicity.
      The reason they have not achieved a significant market share is the cost of
      production, which is considerably higher than for synthetic surfactants. This
      problem is being addressed using several strategies. An approach where there is
      great scope for improvement with the rhodococci is an understanding of the
      genetic basis of glycolipid production, which is largely unknown. They may find
      applications in the near future in the environmental remediation industries,
      where the requirement for purified molecules is of less importance. This review
      summarises knowledge of the chemistry, biochemistry and production of Rhodococcus
      surface-active lipids. Where they have been used, or there is potential for use,
      in industrial applications is discussed.

PMID- 10068790
TI  - The putative regulator of catechol catabolism in Rhodococcus opacus 1CP--an IclR
      type, not a LysR-type transcriptional regulator.
AB  - The catechol catabolic genes catABC from Rhodococcus opacus 1CP have previously
      been characterized by sequence analysis of the insert cloned on plasmid pRER1.
      Now, a 5.1-kb DNA fragment which overlaps with the insert of pRER1 was cloned,
      yielding pRER2, and subjected to sequencing. Besides three other open reading
      frames, a gene was detected ca 200 bp upstream of the catechol 1,2-dioxygenase
      gene catA, which is obviously transcribed divergently from catABC. The protein
      which can be deduced from this gene, CatR, resembles members of the PobR
      subfamily of IclR-type regulatory proteins. This finding was unexpected, as all
      catechol and chlorocatechol gene clusters known thus far from proteobacteria are
      under control of LysR-type regulators. It was not possible to inactivate catR by
      homologous recombination. However, heterologously expressed CatR in vitro bound
      specifically to the intergenic region between catR and catA thereby providing a
      first indication for a possible involvement of CatR in the regulation of catechol
      catabolism.

PMID- 10068791
TI  - A self-compartmentalizing protease in Rhodococcus: the 20S proteasome.
AB  - The 26S proteasome represents a major, energy-dependent and self
      compartmentalizing protease system in eukaryotes. The proteolytic core of this
      complex, the 20S proteasome, is also ubiquitous in archaea. Although absent from
      most eubacteria, this multi-subunit protease was recently discovered in
      Rhodococcus and appears to be confined to actinomycetes. The eubacterial 20S
      proteasome represents an attractive complementary system to study proteasome
      assembly, quaternary structure, and catalytic mechanism. In addition, it is
      likely to contribute substantially to our understanding of the role of various
      self-compartmentalizing proteases in bacterial cells.

PMID- 10068792
TI  - Biotransformation of nitriles by rhodococci.
AB  - Rhodococci have been shown to be capable of a very wide range of
      biotransformations. Of these, the conversion of nitriles into amides or
      carboxylic acids has been studied in great detail because of the biotechnological
      potential of such activities. Initial investigations used relatively simple
      aliphatic nitriles. These studies were quickly followed by the examination of the
      regio- and stereoselective properties of the enzymes involved, which has revealed
      the potential synthetic utility of rhodococcal nitrile biotransforming enzymes.
      Physiological studies on rhodococci have shown the importance of growth medium
      design and bioreactor operation for the maximal conversion of nitriles. This in
      turn has resulted in some truly remarkable biotransformation activities being
      obtained, which have been successfully exploited for commercial organic syntheses
      (e.g. acrylamide production from acrylonitrile). The two main types of enzyme
      involved in nitrile biotransformations by rhodococci are nitrile hydratases
      (amide synthesis) and nitrilases (carboxylic acid synthesis with no amide
      intermediate released). It is becoming clear that many rhodococci contain both
      activities and multiple forms of each enzyme, often induced in a complex way by
      nitrogen containing molecules. The genes for many nitrile-hydrolysing enzymes
      have been identified and sequenced. The crystal structure of one nitrile
      hydratase is now available and has revealed many interesting aspects of the
      enzyme structure in relationship to its catalytic activity and substrate
      selectivity.

PMID- 10068793
TI  - Enantioselective biotransformations using rhodococci.
AB  - The use of enzymes and whole cells in enantioselective biotransformation
      reactions is briefly reviewed. A Rhodococcus strain is shown to possess nitrile
      hydratase and amidase activity. The organism can be used for the enantioselective
      biotransformation of racemic alpha-amino amides to (S) alpha-amino acids with an
      enantiomeric excess (ee) of > 98%. Enantioselectivity is effectively time
      independent allowing easy quantitative conversion of racemic mixtures into
      enantiomerically pure alpha-amino amides and alpha-amino acids. The reaction is
      effective for a wide range of alpha-substituents. The pH-dependence of the
      reaction indicates that the alpha-amino amide is bound to the amidase enzyme in
      its neutral unprotonated form.

PMID- 10068794
TI  - Application of whole cell rhodococcal biocatalysts in acrylic polymer
      manufacture.
AB  - Rhodococci are ubiquitous in nature and their ability to metabolise a wide range
      of chemicals, many of which are toxic, has given rise to an increasing number of
      studies into their diverse use as biocatalysts. Indeed rhodococci have been shown
      to be especially good at degrading aromatic and aliphatic nitriles and amides and
      thus they are very useful for waste clean up where these toxic chemicals are
      present. The use of biocatalysts in the chemical industry has in the main been
      for the manufacture of high-value fine chemicals, such as pharmaceutical
      intermediates, though investigations into the use of nitrile hydratase, amidase
      and nitrilase to convert acrylonitrile into the higher value products acrylamide
      and acrylic acid have been carried out for a number of years. Acrylamide and
      acrylic acid are manufactured by chemical processes in vast tonnages annually and
      they are used to produce polymers for applications such as superabsorbents,
      dispersants and flocculants. Rhodococci are chosen for use as biocatalysts on an
      industrial scale for the production of acrylamide and acrylic acid due to their
      ease of growth to high biomass yields, high specific enzyme activities
      obtainable, their EFB class 1 status and robustness of the whole cells within
      chemical reaction systems. Several isolates belonging to the genus Rhodococcus
      have been shown in our studies to be among the best candidates for acrylic acid
      preparation from acrylonitrile due to their stability and tolerance to high
      concentrations of this reactive and disruptive substrate. A critical part of the
      selection procedure for the best candidates during the screening programme was
      high purity product with very low residual substrate concentrations, even in the
      presence of high product concentrations. Additionally the nitrile and amide
      substrate scavenging ability which enables rhodococci to survive very
      successfully in the environment leads to the formation of biocatalysts which are
      suitable for the removal of low concentrations of acrylonitrile and acrylamide in
      waste streams and for the removal of impurities in manufacturing processes.

PMID- 10068795
TI  - Desulphurisation of benzothiophene and dibenzothiophene by actinomycete organisms
      belonging to the genus Rhodococcus, and related taxa.
AB  - Desulphurising enzymes remove the sulphur moiety from an organosulphur molecule
      leaving the carbon skeleton intact. Two kinds of desulphurisation reaction are
      recognised. The dibenzothiophene (DBT)-specific pathway desulphurises DBT to
      inorganic sulphite and 2-hydroxybiphenyl (HBP), and the benzothiophene (BTH)
      specific pathway desulphurises BTH to 2-(2'-hydroxyphenyl)ethan 1-al (HPEal) and
      probably inorganic sulphite. The DBT-desulphurisation pathway was originally
      identified in Rhodococcus erythropolis strain IGTS8 (ATCC 53968), and the BTH
      desulphurisation pathway in Gordonia sp. strain 213E (NCIMB 40816). These
      organisms do not further metabolise the organic product of desulphurisation. In
      this article current knowledge of the biochemistry and genetics of the
      desulphurisation enzymes is reviewed. The need for separate, DBT- and BTH
      specific desulphurisation routes is rationalised in terms of the chemical
      differences between the two compounds. The desulphurisation pathway is compared
      with other microbial DBT-degrading enzyme systems. Finally some comments are made
      concerning the application of desulphurisation enzymes for fuel desulphurisation
      and on the relevance of these enzymes to the ecology of the mycolata (sensu Chun
      et al, 1996).

PMID- 10068796
TI  - Applied aspects of Rhodococcus genetics.
AB  - Eubacteria of the genus Rhodococcus are a diverse group of microorganisms
      commonly found in many environmental niches from soils to seawaters and as plant
      and animal pathogens. They exhibit a remarkable ability to degrade many organic
      compounds and their economic importance is becoming increasingly apparent.
      Although their genetic organisation is still far from understood, there have been
      many advances in recent years. Reviewed here is the current knowledge of
      rhodococci relating to gene transfer, recombination, plasmid replication and
      functions, cloning vectors and reporter genes, gene expression and its control,
      bacteriophages, insertion sequences and genomic rearrangements. Further
      fundamental studies of Rhodococcus genetics and the application of genetic
      techniques to the these bacteria will be needed for their continued
      biotechnological exploitation.

PMID- 10068797
TI  - Cloning of genes that have environmental and clinical importance from rhodococci
      and related bacteria.
AB  - Generalised and specialised transduction systems were developed for Rhodococcus
      by means of bacteriophage Q4. The latter was used in conjunction with DNA from an
      unstable genetic element of R. rhodochrous to construct resistance plasmids which
      replicate in strains of R. equi, R. erythropolis and R. rhodochrous. One of the
      plasmids, pDA21, was joined with Erythropolis coli suicide vector pEcoR251 to
      obtain shuttle plasmids maintained in both rhodococci and E. coli. Conjugation
      between these rhodococcal strains demonstrated all were interfertile with each
      other and that some of the determinants for this were located on the unstable
      genetic element. Plasmids derived from this element, such as pDA21, carried the
      conjugative and self-incompatibility capacities; deletion analysis revealed that
      DNA necessary for self-incompatibility overlapped with that for arsenic
      resistance. Rifampicin is one of the principal chemotherapeutic agents used to
      treat infections by rhodococci and related organisms. The genes responsible for
      two types of inactivation have been cloned. The sequence of the R. equi DNA
      responsible for decomposition of the antibiotic strongly resembled those of
      monooxygenases acting upon phenolic compounds, consistent with the presence of a
      naphthalenyl moiety in the rifampicin molecule. Antibiotic resistance conferred
      by the gene was surprisingly specific to the semisynthetic compounds rifampicin
      (150-fold increase) and rifapentine (70-fold). Similar specificity was observed
      with the other inactivation gene cloned, which ribosylates rifampicin at the 23
      hydroxyl position. A 60-bp sequence upstream of the monooxygenase and
      ribosylation genes is strikingly similar suggesting a shared pattern of
      regulation. Rhodococcal arsenic resistance and azo dye degradation genes have
      been cloned and characterised.

PMID- 10068798
TI  - Structural alteration of linear plasmids encoding the genes for polychlorinated
      biphenyl degradation in Rhodococcus strain RHA1.
AB  - Polychlorinated biphenyl (PCB) tolerant derivatives of a strong PCB degrader,
      Rhodococcus strain RHA1, were selected after growth in the presence of 100
      micrograms/ml PCBs. Some of the derivatives did not grow on biphenyl but
      accumulated a yellow coloured metabolite suggesting a defect in the meta-ring
      cleavage compound hydrolase step encoded by the bphD gene. Other derivatives
      failed to grow on biphenyl and exhibited little PCB transformation activity
      suggesting a defect in the initial ring-hydroxylation dioxygenase step encoded by
      the bphA gene. These organisms had a structural alteration in the linear plasmids
      coding for the bph genes in RHA1, which included the bph gene deletion. When a
      bphD containing plasmid was introduced into a tolerant derivative, RCD1, which
      was shown to have bphD deletion, the defect in the growth on biphenyl of RCD1 was
      overcome. The bph gene deletion seems to play a key role in these tolerant
      derivatives thereby suggesting that the toxic metabolic intermediate would be a
      main cause of the growth inhibition of RHA1 in the presence of high concentration
      PCBs.

PMID- 10068799
TI  - Molecular characterisation of a Rhodococcus ohp operon.
AB  - The ohp operon of Rhodococcus strain V49 consists of five genes, ohpR, ohpA,
      ohpB, ohpC and ohpD which encode putative regulator and transport proteins and
      confirmed monooxygenase, hydroxymuconic semialdehyde hydrolase and catechol 2,3
      dioxygenase enzymes, respectively. These enzymes catalyse the conversion of 3-(2
      hydroxyphenyl)propionic acid to the corresponding linear product via a meta
      cleavage pathway. Confirmation that the ohp gene cluster formed an operon was
      provided by gene disruption during which expression of Bacillus levansucrase was
      confirmed in Rhodococcus. Following biochemical assays of cell-free extracts from
      recombinant Escherichia coli expressing ohpB (monooxygenase), ohpC
      (hydroxymuconic-semialdehyde hydrolase) and ohpD (catechol 2,3-dioxygenase), the
      ortho-hydroxyphenylpropionic acid catabolic pathway in Rhodococcus strain V49
      (ATCC 19070) has been predicted.

PMID- 10068800
TI  - Can SPECT predict the future for mild cognitive impairment?

PMID- 10068801
TI  - The world of touch--from evoked potentials to conscious perception.
AB  - Microelectrode recordings have enabled several maps of the body surface to be
      recognized in the mammalian somatosensory cortex. The maps appear to represent
      increasingly complex levels of analysis of the sensory message. At present the
      prevailing opinion is that the different components of the ERPs (event related
      potentials) represent sequential steps in such an analysis, and such an
      interpretation is supported by the enhancement of the ERPs when attention is paid
      to a somatic stimulus. However, there are a number of critical observations which
      are inconsistent with this view and suggest that the ERP enhancement may be an
      epiphenomenon. An alternative explanation for the ERPs is that they reflect
      discharges from the non-specific thalamic nuclei, and are essentially similar to
      the long latency responses which can be recorded from the cortex during sleep or
      anaesthesia. Lastly, a hypothesis is proposed for the neuronal events in the
      somatosensory cortex which culminate in a conscious perception. In this "RULER"
      model, the deep pyramidal neurones read out the sensory information which has
      been retained in the apical dendrites of more superficial cells, and do so at the
      end of successive "time-chunks".

PMID- 10068802
TI  - Low grade glioma: a measuring radiographic response to radiotherapy.
AB  - PURPOSE: We set out to determine the rate of response of low-grade (WHO Grade II)
      gliomas to radiotherapy and analyze the relationship between radiographic
      response, symptom control and patient survival. METHODS: Patients were eligible
      for this study if they had received radiotherapy for pathologically confirmed,
      residual, supratentorial low-grade astrocytoma, oligodendroglioma, or mixed
      glioma, and imaging studies (baseline and follow-up) were available for review.
      Percent change in tumor size and rate and timing of response were determined by
      maximum linear measurement, area measurement, volume measurement using an
      ellipsoid model, and volume measurement by image segmentation. For each method,
      response to radiotherapy was defined firstly as a > or = 50% decrease in tumor
      size (partial response), and secondly as a decrease equivalent to a 50% area
      decrease (normalized partial response). Relationships between radiographic
      response, clinical improvement and progression-free survival were analyzed using
      a Cox Proportional Hazard's model. RESULTS: Twenty-one patients in a database (13
      male, 8 female; ages 22-66 years) met the eligibility criteria. Twenty were
      imaged by computed tomography, 18 had an astrocytoma and 15 were irradiated soon
      after surgery. Responses were common and not felt to be due to a steroid effect.
      Use of normalized response criteria improved agreement between assessment of
      response as determined by the 4 methods. Median time to maximum radiographic
      improvement was 2.8 months (range, 1.5-11). Sixteen patients (76%) were improved
      neurologically, the median time to progression was 4.8 years and the 5-year
      progression-free survival rate was 43%. We did not detect a statistically
      significant association between response (as measured by any method),
      symptomatology and progression-free survival. CONCLUSIONS: Low-grade gliomas are
      moderately radioresponsive. Use of volume measurement may over-estimate the
      number of partial responses unless a volume reduction equivalent to a 50% area
      decrease is used to define response. The best way to measure response remains
      uncertain because neither visual, area, nor volume changes confidently predicted
      clinical outcomes.

PMID- 10068803
TI  - Lack of prognostic significance of SPECT abnormalities in non-demented elderly
      subjects with memory loss.
AB  - OBJECTIVE: To determine if hypoperfusion abnormalities on single photon emission
      computed tomography (SPECT) are associated with poorer cognitive function at
      baseline or increased risk of decline in cognitive function and progression to
      dementia in memory-impaired but non-demented elderly subjects meeting the
      criteria for aging associated cognitive decline (AACD). DESIGN: Cross sectional
      study of 36 AACD subjects comparing hexamethyl propylene-amine oxime (HMPAO)
      SPECT results rated by visual inspection with base line cognitive functioning.
      Prospective study of these AACD subjects with clinical and neuropsychological
      follow-up over 35 months. SETTING: The memory clinic and nuclear medicine unit of
      a university teaching hospital. SUBJECTS: Thirty-six subjects meeting the
      criteria for AACD recruited from patients seen on a physician referral basis.
      MAIN OUTCOME MEASURES: 1) Baseline cognitive function as measured by the Mini
      Mental State Examination (MMSE), Boston naming, Logical Memory I subtest of the
      WAIS-R, and verbal fluency, correlated with SPECT status. 2) Decline in cognitive
      function as measured by clinical exam and the MMSE, with progression to dementia
      on follow-up being correlated with SPECT status at baseline. RESULTS: 18 of the
      36 subjects progressed to dementia (probable Alzheimer's Disease) over follow-up.
      No correlation was found between the presence or absence of SPECT abnormality and
      MMSE or other cognitive measures. There was no correlation between the presence
      or absence of SPECT abnormality at initial examination, and cognitive decline
      according to the MMSE, or with the occurrence of clinical dementia on follow-up.
      CONCLUSIONS: We conclude that SPECT abnormalities assessed by visual inspection
      do not correlate with severity of impairment in AACD individuals, and are not
      useful in predicting progression to dementia in AACD subjects.

PMID- 10068804
TI  - Herpes zoster and multiple sclerosis.
AB  - BACKGROUND: Clinical experience suggests that young multiple sclerosis patients
      may have herpes zoster (HZ) earlier and more often than the general population.
      As there is evidence of a relationship between varicella zoster virus (VZV) and
      MS, a study of HZ and MS was undertaken. METHODS: Eight hundred and twenty-nine
      patient-members of the Manitoba Chapter of the Canadian Multiple Sclerosis
      Society were surveyed by mail. Six hundred and thirty-three (76%) responded.
      Questions included: age at diagnosis of MS, history of HZ (yes, no, probably),
      number of episodes of HZ and age at each occurrence, date of birth, and sex of
      respondent. The controls were consecutive patients with other neurological
      diseases (OND) attending local neurological or neurosurgical clinics, plus
      practice-based and population-based surveys of herpes zoster without reference to
      any other disease. The OND controls were assessed at the time of their outpatient
      visits. RESULTS: In the MS group with a positive/probable history of HZ, the
      HZ/MS rate was 106/633 (16.8%); in the practice-based survey the rate was
      192/3534 (5.4%); and among the patients with OND it was 42/616 (6.8%). The HZ
      occurred at an earlier age in the MS group. The majority of male patients had HZ
      prior to the diagnosis of MS. The date of diagnosis is more likely to be a
      precise memory as opposed to the onset of symptoms. More than one attack of HZ
      was also more common in the MS group. CONCLUSIONS: This survey adds to the
      evidence that patients with MS have a unique relationship with the herpes zoster
      virus.

PMID- 10068805
TI  - Role of electrocorticography at surgery for lesion-related frontal lobe epilepsy.
AB  - BACKGROUND: The prognostic significance of epileptiform activity (EA) recorded
      intraoperatively at electrocorticography (ECOG) in patients with lesion-related
      frontal lobe epilepsy (FLE) is unknown. METHODS: The results of ECOG performed in
      22 patients with intractable FLE and a circumscribed frontal lobe structural
      lesion were compared with postoperative seizure control. Three patients underwent
      re-operation for a total of 25 cases, 23/25 with post-resection ECOG. Lesions
      were neoplasms (12), hamartomas (6) and arteriovenous malformations (4). RESULTS:
      Outcomes were 15/25 Class I, 5/25 Class III and 5/25 Class IV (Engel
      classification). Class I outcome was associated with pre-excision EA recorded
      from < or = 2 gyri (p < 0.05) and absence of EA, or EA limited to the resection
      border, at post-excision ECOG (p < 0.01). Complete lesion excision was highly
      correlated with Class I outcome (p < 0.001). The most significant correlations
      were seen when ECOG and lesionectomy variables were considered together: all 12
      cases with complete lesionectomy and absent post-excision EA distant to the
      resection border had Class I outcome (p < 0.00015) and all 13 cases with complete
      lesionectomy and pre-excision EA recorded from < or = 2 gyri had Class I outcome
      (p < 0.00005). CONCLUSIONS: Postoperative seizure control in lesion-related FLE
      is assured in the setting of complete lesion resection with pre-excision EA
      recorded from < or 2 gyri and no post-excision EA distant to the resection
      border; complete lesion excision is of paramount importance.

PMID- 10068806
TI  - The reliability of the "absent cistern sign" in assessing LP shunt function.
AB  - OBJECTIVE: One of the difficulties with lumboperitoneal (LP) shunts has been non
      invasively ascertaining shunt function. It has been previously reported that in
      the presence of a functioning LP shunt the perimesencephalic cisterns become
      obliterated--the "absent cistern sign". In order to more rigorously test this
      association we performed a retrospective analysis of LP shunt patients at the
      Hospital for Sick Children, Toronto. METHODS: The CT scans of all patients
      undergoing LP shunting over a 17 year period were reviewed. The "absent cistern
      sign" and ventricular size were compared against the results of either an isotope
      shunt study or surgical findings performed within 2 days of the CT. RESULTS:
      There were 38 CT scans (27 patients) performed within 2 days of an isotope shunt
      study and 15 CT scans (14 patients) performed within 2 days of a surgical
      intervention. These results give the absent cistern sign a sensitivity of 75% and
      a specificity of 57% when compared to the shunt isotope findings and a
      sensitivity of 100% and a specificity of 50% when compared to the surgical
      findings. Over 30% of the CT scans showed ventriculomegaly in the presence of a
      functioning shunt and, conversely, nearly 45% of the CT scans had normal or small
      lateral ventricles in the presence of a malfunctioning shunt. CONCLUSIONS: The
      "absent cistern sign" appears to reliably rule out a completely blocked shunt,
      but is less reliable in detecting a normal or partially obstructed shunt.
      Ventricular size correlates poorly with LP shunt function.

PMID- 10068807
TI  - Intraoperative loss of auditory function relieved by microvascular decompression
      of the cochlear nerve.
AB  - BACKGROUND: Brainstem auditory evoked potentials (BAEP) are useful indicators of
      auditory function during posterior fossa surgery. Several potential mechanisms of
      injury may affect the cochlear nerve, and complete loss of BAEP is often
      associated with postoperative hearing loss. We report two cases of intraoperative
      auditory loss related to vascular compression upon the cochlear nerve. METHODS:
      Intra-operative BAEP were monitored in a consecutive series of over 300
      microvascular decompressions (MVD) performed in a recent twelve-month period. In
      two patients undergoing treatment for trigeminal neuralgia, BAEP waveforms
      suddenly disappeared completely during closure of the dura. RESULTS: The
      cerebello-pontine angle was immediately re-explored and there was no evidence of
      hemorrhage or cerebellar swelling. The cochlear nerve and brainstem were
      inspected, and prominent vascular compression was identified in both patients. A
      cochlear nerve MVD resulted in immediate restoration of BAEP, and both patients
      recovered without hearing loss. CONCLUSION: These cases illustrate that vascular
      compression upon the cochlear nerve may disrupt function, and is reversible with
      MVD. Awareness of this event and recognition of BAEP changes alert the
      neurosurgeon to a potential reversible cause of hearing loss during posterior
      fossa surgery.

PMID- 10068808
TI  - Near-infrared spectroscopy monitored cerebral venous thrombolysis.
AB  - BACKGROUND: Cerebral venous thrombosis is a clinical entity which is readily
      diagnosed with the advent of modern imaging techniques. Anticoagulation is now a
      standard therapy, but more recent treatment strategies have included endovascular
      thrombolysis. While the endpoint of this intervention both clinically and
      radiographically has not been defined, noninvasive monitoring techniques may add
      further objective measures of treatment response. CLINICAL PRESENTATION: We
      present a patient with a four day history of worsening headache and papilledema
      on exam. Superior sagittal, straight, and bilateral transverse sinus thromboses
      were identified on computed tomography and angiography. INTERVENTION: Emergent
      endovascular thrombolysis by a transvenous approach re-established venous patency
      and resulted in immediate resolution of the patient's symptoms. Cerebral oximetry
      by near-infrared spectroscopy was utilized during the procedure, and changes in
      chromophore concentrations correlated directly with angiographic and clinical
      resolution of the thrombosis. CONCLUSION: Near-infrared spectroscopy can provide
      continuous feedback during thrombolytic therapy in cerebral venous thrombosis and
      may help define endpoints of such intervention.

PMID- 10068809
TI  - Phantom erection after amputation of penis. Case description and review of the
      relevant literature on phantoms.
AB  - BACKGROUND: Perception of a phantom limb is frequent after an amputation of an
      upper or lower extremity. Phantom penis is reported infrequently. METHOD: Case
      description and literature review. RESULT: The phenomenon of phantom penis
      followed total penectomy. Several aspects were unusual, particularly the
      existence with phantom only in the erect state, and associated recrudescence of a
      preoperative painful ulcer. General features of limb phantoms after amputation
      are reviewed including a resume of recent studies of cortical reorganization. The
      phantom process is analyzed looking for clues to the nature of the underlying
      neural organization. The puzzle of phantom pain is briefly touched on.
      CONCLUSION: The development of the phantom is attributed to activity in the
      deafferented parietal sensory cortex.

PMID- 10068810
TI  - Pseudo-subarachnoid hemorrhage: a rare neuroimaging pitfall.
AB  - OBJECTIVE: We report an unusual case of the CT appearance of diffuse subarachnoid
      hemorrhage in a patient with anoxic encephalopathy, a situation which
      neurosurgeons, neurologists, and neuroradiologists should be aware of. CLINICAL
      PRESENTATION: A young man collapsed unconscious in jail after abusing an unknown
      quantity and variety of drugs. CT scan showed a picture compatible with diffuse
      subarachnoid hemorrhage. INTERVENTION: As the patient had a Glasgow Coma Score of
      3 no heroic intervention was undertaken. An autopsy performed 40 hours after the
      initial ictus and 24 hours after death revealed no evidence of subarachnoid
      hemorrhage but gross and microscopic evidence of anoxic encephalopathy.
      CONCLUSION: Anoxic encephalopathy can mimic diffuse subarachnoid hemorrhage on
      CT.

PMID- 10068811
TI  - MRI in vitamin B12 deficiency myelopathy.
AB  - BACKGROUND: Little is known about vitamin B12 deficiency myelopathy's magnetic
      resonance imaging (MRI) manifestations and their relationship to the onset,
      evolution, and resolution of neurologic signs and symptoms. METHODS: We present a
      case and review eleven additional reported cases of subacute combined
      degeneration of the spinal cord detected by MRI. RESULTS: Our patient had
      increased T2-weighted signal and gadolinium contrast enhancement of the posterior
      columns in the cervical and thoracic regions and enhancement of the lateral
      columns in the high cervical region. This is a case with imaging evidence for
      lateral column lesions. Two prior reports have shown posterior column
      enhancement. T1-weighted images may show decreased signal in the posterior
      columns and sometimes demonstrate reversible spinal cord swelling. MRI
      abnormalities typically improve after vitamin replacement therapy. However,
      clinical signs may persist despite resolution of imaging abnormalities, and these
      abnormalities do not always resolve completely. In addition, symptoms may precede
      the imaging abnormality. CONCLUSIONS: Vitamin B12 deficiency may produce an
      increased T2-weighted signal, decreased T1-weighted signal, and contrast
      enhancement of the posterior and lateral columns of the spinal cord, mainly of
      the cervical and upper thoracic segments. Because the symptoms may precede any
      imaging abnormality, it is clear that spinal cord MRI may not be a highly
      sensitive, early test for subacute combined degeneration.

PMID- 10068812
TI  - Guidelines for the diagnosis of brain death. Canadian Neurocritical Care Group.

PMID- 10068813
TI  - [In Process Citation]

PMID- 10068814
TI  - [In Process Citation]
AB  - Intensive care of the surgical patient is an integral part of the treatment and
      continuing medical education mission of surgery. Working on the intensive care
      unit educates surgeons with regard to emergency treatment, pathophysiological
      thinking, and judging the risks of surgical procedures. The importance of
      preoperative workup and postoperative care and the diagnosis of postoperative
      complications are experienced personally and should thus encourage the surgeon to
      operate nontraumatically and increase their motivation for continuous holistic
      patient care. This does not mean erecting boundaries or competing with
      anesthesiologists in surgical intensive care. Rather, the joint aims of surgeons
      and anesthesiologists should be reinforced. The advantages of close cooperation
      for successful completion of the mission of patient care and medical education
      for younger colleagues need to be emphasized. Ideal cooperation between
      anesthesiologists and surgeons calls for commitment, competence, trust, and
      personal accord on the part of the persons involved. Under these circumstances,
      even in hospitals with only one interdisciplinary intensive care unit there
      should be no problems regarding who takes on official leadership.

PMID- 10068815
TI  - [In Process Citation]
AB  - Intensive care medicine for both surgical and medical patients has a common
      scientific and clinical basis. In critically ill patients the medical conditions
      are complex and can be managed only by specialists thoroughly trained in
      intensive care medicine. Therefore, surgeons as well as anesthesiologists must
      have a detailed theoretical and clinical knowledge of intensive care medicine.
      Surgical training places the emphasis on operative skills, while intraoperative
      management of the patient by the anesthesiologist calls for skills involved in
      intensive care medicine. Interdisciplinary cooperation between specialists is
      essential to improve the quality of intensive care medicine further. The
      cooperation that already exists between surgeons and anesthesiologists makes
      closer collaboration in the future a logical step.

PMID- 10068816
TI  - [In Process Citation]
AB  - The complexity of daily clinical work requires a sophisticated collaboration of
      surgery and anesthesiology. This can be accomplished by a rational approach to
      the following topics: clear definition of areas of competence respecting the
      principle of mutual trust, integration of anesthesiologists into the basic
      physical examination, proposal of case-oriented preoperative diagnostics,
      agreement on necessary preoperative therapy, common consultational meetings for
      outpatient surgery, recovery room available 24 h a day, instruction of the
      surgical personnel in specific pain therapy, availability of coworkers who are
      competent and willing to cooperate, no unilateral renunciation of clinical
      knowledge, ability and execution, no renunciation of organizational and
      structural self-determination, no monopoly on perioperative medicine.

PMID- 10068817
TI  - [In Process Citation]
AB  - Soaring health care costs are also forcing surgeons and anaesthesiologists to
      introduce practice patterns that allow more efficient use of expensive hospital
      resources. Because perioperative ward expenditures account for approximately one
      third of the hospital costs incurred for surgical inpatients, with personnel
      costs being a major component, interventions that decrease the length of stay can
      result in considerable savings without affecting the quality of care.
      Interventious that can reduce the length of stay are outpatient preoperative
      evaluation and same-day admission, improvement of OR efficiency and sufficient
      cost-effective facilities for qualified postoperative care.

PMID- 10068818
TI  - [In Process Citation]
AB  - The increasing number of high-risk patients and the limited number of intensive
      care beds and shrinking hospital budgets make it necessary to review
      perioperative management processes. Analyzing the data of the Heidelberg
      Anesthesia documentation system revealed improvement strategies in operating room
      management. The coordination of all groups involved is optimized by an operating
      room management group. This independent group plans and coordinates the operating
      room procedures, together with emergency cases according to personal, room and
      specific needs. Establishment of a holding area and a postoperative anesthesia
      care unit next to central operating units will significantly improve the
      perioperative organization processes. Redistribution of personnel enables
      intermediate care units to be opened, which provide additional intensive care bed
      capacity.

PMID- 10068819
TI  - [In Process Citation]
AB  - Perioperative management requires close cooperation between the referring
      practitioner, anesthesiologist, surgeon, and nursing staff. Standards in
      diagnostics, risk assessment, and choice of procedure, as well as integration of
      the anesthesiologist into the surgical out-patient department, are all important
      prerequisites for the optimum preparation of patients. Elective operations are to
      be planned in advance, taking into account the surgical resources available.
      Additional operating rooms with interdisciplinary access should be available for
      emergency procedures. Turnaraound times between operations can be reduced by
      separate rooms for pre- and postsurgical preparation and recovery. Small
      functional units allow for a flexible response to necessary changes in the
      schedule. These measures increase the quality of treatment and economic
      efficiency, as well as the satisfaction of patients and staff.

PMID- 10068820
TI  - [In Process Citation]
AB  - Solid tumors do not grow beyond a size of a few millimetres without supply of
      nutrients and growth factors by the vascular system. Only when tumors produce
      angiogenic growth factors new vessels are formed by sprouting of capillaries from
      the existing vascular system. The tumor can grow and tumor cells reach the
      circulation through these new and permeable vessels. The vascular endothelial
      growth factor (VEGF) is the most prominent angiogenic growth factor. VEGF is
      produced by almost all solid tumors: its receptors are expressed only on vascular
      endothelial cells and predominantly in vessels in the proximity of the tumor.
      Therefore, the VEGF/VEGF-receptor system is a target for anti-angiogenic cancer
      therapy. Experiments show that inhibition of the VEGF-mediated endothelial cell
      activation interferes with tumor growth and metastases formation. Appropriate
      therapeutic strategies are currently under clinical investigation.

PMID- 10068821
TI  - [In Process Citation]
AB  - Video-assisted thoracoscopic surgery is now recommended for the treatment of
      primary spontaneous pneumothorax. We studied the validity of this method at our
      general surgical department in a prospective group with regard to effectiveness
      and complication rate. The combination of thoracoscopic bulla resection with
      tetracycline pleurodesis resulted in a 100% recurrence-free rate of 28
      pneumothoraces at a median follow-up of 19 months. We observed no intraoperative
      complications. We conclude that video-assisted thoracoscopic surgery is an
      effective treatment for primary spontaneous pneumothorax and can safely be
      carried out even in a general surgical unit. The legal aspects are discussed in
      detail.

PMID- 10068822
TI  - [In Process Citation]
AB  - Intraoperative radiotherapy (IORT) is a new concept in the treatment of recurrent
      and primary advanced colorectal tumors. Between October 1994 and December 1997 27
      patients (primary tumor: 8, first recurrent tumor: 12, second recurrent tumor: 7)
      received IORT (32 applications). Chemotherapy and percutaneous radiotherapy had
      already been given to all patients with advanced and recurrent colorectal tumors.
      The intraoperative irradiation was performed through HDR iridium afterloading. A
      flexible flab--individually adapted to the "tumor bed"--was used as applicator.
      The contact dose ranged from 10 to 15 Gy. The mean operation time (rectum
      resection: 5, rectum amputation: 14, debulking: 8) increased by 30 min on
      average. Eight patients had postoperative complications: perianal wound
      infections (3), sacrovesical fistulas (3), leakage of anastomosis (1) and neural
      ureter dysfunction (1). To date--on average 17.1 months (range: 3-33) after
      operation--13 patients are free of tumor recurrence or show stable disease. Ten
      patients--all of them had macroscopic residual tumor--have local tumor
      progression combined with good quality of life. Only 4 patients died (acute
      kidney failure, stroke, marasmus, systemic progression). The afterloading flab
      technique represents a technically simple, minimally harmful procedure in the
      therapy of colorectal tumor. Even when IORT with electrons is not feasible or the
      patients have already been irradiated, a higher radiation dose is possible. Given
      the demonstrated rate of local tumor recurrence, the afterloading flab technique
      seems to be a valuable treatment alternative to extended, high-risk resections.
      Long-term follow-ups will be necessary.

PMID- 10068824
TI  - [In Process Citation]

PMID- 10068823
TI  - [In Process Citation]
AB  - BACKGROUND: Although the majority of surgeons regard Hartmann's operation as
      therapeutic standard in perforations of the colon complicated by peritonitis this
      procedure has been critically discussed in recent years. Advocates of one-stage
      techniques criticized bad postoperative results (high morbidity and mortality)
      and long-term outcome (low rates of intestinal restoration). The aim of our study
      was to investigate whether the late results after Hartmann's operation justify
      this criticism. METHOD: From 1982 to 1997 Hartmann's operations were performed in
      103 patients for colonic perforations. In 63% of cases inflammatory diseases
      caused colonic complications. The average Mannheimer Peritonitis Index (MPI) was
      19. Seventeen patients died postoperatively (mortality: 16.5%). In 69 patients
      (80%) intestinal restoration could be performed after an average interval of 122
      days (complication rate: 6%, no mortality). On follow-up, patients were asked to
      give information on their general state, changes of housing, abdominal
      complaints, and quality of life. RESULTS: Data on 93% of patients could be
      obtained. The median follow-up time was 75 months. Eleven patients had died; the
      remaining 72 were investigated. 86% described the quality of their lives as good
      or very good; only 11% indicated severe loss of activity. Quality of life did not
      differ between patients in whom intestinal continuity had been restored and those
      in whom it had not been restored. Anastomotic structures developed in 7% of
      cases, always after stapled anastomosis. CONCLUSIONS: According to our results,
      long-term outcome after Hartmann's operation is good. 80% of patients underwent
      intestinal restoration with low morbidity (6%) and no mortality. A great majority
      of patients indicated the quality of their lives as good or very good: this
      assessment was not dependent on restoration of intestinal continuity.

PMID- 10068825
TI  - [In Process Citation]

PMID- 10068826
TI  - [In Process Citation]

PMID- 10068827
TI  - [In Process Citation]

PMID- 10068828
TI  - [In Process Citation]

PMID- 10068829
TI  - [In Process Citation]

PMID- 10068830
TI  - [In Process Citation]

PMID- 10068831
TI  - [In Process Citation]
AB  - Twenty-seven patients presenting with complete rectal prolapse were treated by
      extracorporal resection using a stapling device. The mean age of the female
      patients was 74 +/- 15 years, the mean operation time 61 +/- 17 min, the mean
      length of hospital stay 17 +/- 8 days. 96% of the patients suffered from at least
      one concurrent disease necessitating treatment. Perioperative mortality was 3.7%,
      postoperative complications occurred in 18% of our patients. After surgery 19% of
      the patients were incontinent. Extracorporal resection using a stapling device
      proves to be a secure and technically easy-to-perform procedure in the treatment
      of complete rectal prolapse. Due to several advantages compared with
      transabdominal procedures, the indication for perineal repair of a complete
      rectal prolapse by extracorporal resection should not be confined to high-risk
      patients.

PMID- 10068832
TI  - [In Process Citation]
AB  - The aim of this study was to investigate postoperative und long-term results
      after radical tumor surgery in complicated colorectal cancers. One hundred and
      twenty-six (11.7%) of 1071 patients treated for large bowel cancer between 1986
      and 1997 were operated on for bowel obstruction (84; 7.8%): or perforation (42;
      3.9%). Postoperative mortality was significantly higher in complicated than in
      uncomplicated cancers (19% after bowel obstruction, 38% after perforation, 6% in
      uncomplicated cases). Development of preoperative organ dysfunction determined
      survival in both complications. Mortality after perforations was influenced by
      the degree of peritonitis and tumor stage, while patients after bowel obstruction
      were at greater risk in the case of cardiac comorbidity. Long-term results
      depended on tumor stage but not on complications. Our concept of radical tumor
      surgery in emergency operations was supported by the fact that long-term results
      of patients surviving the acute stage of complicated colorectal cancers did not
      differ from those of patients with uncomplicated carcinomas.

PMID- 10068833
TI  - [In Process Citation]
AB  - Mechanical ventilation is a well-established strategy in intensive care medicine.
      ICU trauma patients require analgesia, and sedation mostly consists of
      benzodiazepines and opioids with increasing doses over time. The weaning period
      is complicated by the withdrawal syndrome, showing tachycardia, hypertonia,
      tachypnea and restlessness. Although treatment with clonidine can influence these
      symptoms, tachypnea still remains the main problem in weaning patients from
      mechanical ventilation. Adding sufentanil, an opioid with greater effects on
      analgesia than on respiratory depression compared with fentanyl, tachypnea can be
      reduced to normal frequency. In this way weaning management can be managed more
      easily for the benefit of both, the patient and physician. In comparison with a
      group of 50 patients treated with clonidine alone, 72 patients treated with
      clonidine/sufentanil showed a shorter period from the start of spontaneous
      ventilation until extubation (4.8 vs 7.6 days) and until discharge from the ICU
      (7.7 vs 12.4 days). The number of reintubations caused by respiratory exhaustion
      decreased from 16.0 to 2.8%.

PMID- 10068834
TI  - [In Process Citation]
AB  - Since 1996 thoracic surgery has been invoiced according to fixed reimbursement
      rates (Sonderentgelte, SE). The legislator argues that fixed reimbursement rates
      cover operation costs and justify a 20% reduction in reimbursement for nursing.
      In order to examine this assumption we performed a cost analysis of thoracic
      surgery. Taking into account the staff, equipment, and operating theatre
      supplies, we analyzed 30 cases of five different types of operation prospectivly:
      wedge resections with more than three wedges (AR: n = 8), lobectomies (LE: n =
      8), pneumonectomies (PE: n = 5), thoracoscopic wedge resections (VR: n = 6) and
      resections of mediastinal tumors (MR: n = 3). Then we calculated the overall
      costs for each operation. The costs for a LE amounted to DM 9,927, which is DM
      4,904 more than the corresponding fixed reimbursement rate. The costs were DM
      11,562 for a PE, DM 12,477 for a VR and DM 7,532 for a MR. Thus the costs were DM
      5,539, DM 2,435 or DM 1,907 higher than the corresponding fixed reimbursement
      rates. The fixed reimbursement rate for an AR was DM 866 higher than the actual
      cost of DM 6,922. Only for a small number of cases do the fixed reimbursement
      rates cover the actual costs of thoracic surgery. Thus operation costs still need
      to be at least partly covered by the reimbursement for nursing.

PMID- 10068835
TI  - [In Process Citation]
AB  - Cryophlebectomy, a more recent technique in varicose veins surgery, was evaluated
      in comparision with conventional techniques. Group IA: Microphlebectomy,
      invaginative stripping of the long saphenous vein, tourniquet, n = 90; group IB:
      only microphlebektomie and tourniquet, n = 72. Group IIA: Cryostripping of the
      long saphenous vein in combination with cryosurgical distal avulsion of
      varicosities and microphlebectomy, n = 112; gr. IIB: only cryosurgical distal
      avulsion of varicosities and microphlebectomy. Data were compared regarding
      duration of operation and hospitalisation and cosmetic outcome. Hospital stay
      (gr. IA: 9.1 +/- 5.1 d vs. gr. IIA: 6.1 +/- 2.1 d, gr. IB: 5.5 +/- 2.3 d vs. gr.
      IIB: 4.8 +/- 2.5 d) and duration of operation (gr. IA: 113.6 +/- 35 min vs. gr.
      IIA: 67 +/- 21.3 min, gr. IB: 74.4 +/- 35.3 min vs. gr. IIB: 53.3 +/- 15.5 min)
      were found to be significantly shorter and cosmetic result and postoperative
      discomforts improved in the cryophlebectomy-group. We conclude that the use of
      this combination of methods reduces invasivity, rises the patient's well-being
      and helps in cost-reduction.

PMID- 10068836
TI  - [In Process Citation]
AB  - Intimal sarcoma of the pulmonary artery is an extremely rare type of malignant
      tumor of the large vessels. Despite systematic diagnostics, distinguishing
      between pulmonary emboli and tumors is difficult. We report a patient who was
      referred because of suspected embolic occlusion of the pulmonary artery. The
      operation was started with the intention of performing a pulmonary artery
      thromboendarterectomy; however, intraoperative histology revealed a malignant
      mesenchymal tumor. Therefore, the left lung was resected with the use of
      extracorporeal circulation, and the pulmonary trunk and right pulmonary artery
      were reconstructed. A solitary right lung metastasis was resected 3 months later
      using stapling devices. Complete surgical resection is the treatment of choice
      for patients with sarcoma of the pulmonary arteries. Surgical therapy often
      includes extensive reconstructive measures. Since, thromboembolic obstruction
      cannot be excluded preoperatively, patients with this type of disease should be
      treated at centers experienced with the broad spectrum of pulmonary artery
      surgery.

PMID- 10068837
TI  - [In Process Citation]
AB  - Mesenteric cysts are a rare cause of disease. In our hospital we treated one
      patient who suffered from bilateral ureteral obstruction followed by
      hydronephrosis, caused by a large mesenteric cyst. Because of its extent complete
      enucleation--the surgical procedure of choice--was not possible. We opened the
      cyst and made an external percutaneous drainage. After this treatment the patient
      recovered and even after 6 months there was no recurrence.

PMID- 10068838
TI  - [In Process Citation]
AB  - Adrenocortical insufficiency (Addison's disease) is a functional diagnosis. At
      the beginning of this century, tuberculosis was recognized as the main
      etiological cause (50-70%). Today, however, tuberculosis represents only 10% of
      the cases. Adrenocortical insufficiency is mainly caused by autoimmune
      adrenalitis (more than 50%). Unilateral adrenocortical disease is usually
      asymptomatic or presents, as in the case described, with minor symptoms. This
      case report of adrenal tuberculosis illustrates the current challenges of
      diagnosis and therapy.

PMID- 10068839
TI  - [In Process Citation]
AB  - To optimise the microsurgical training in our clinic we organized a permanent
      possibility to practice microsurgical techniques of vascular anastomosis. This
      includes step-wise education by means of plastic materials, human placenta and
      the rat model. The most important role in this concept is played by the placenta.
      It supplies a realistic simulation of different in vivo situations concerning
      microvascular anastomosis. As to availability, handling and costs the placenta is
      superior to animal models and has replaced them almost completely in our
      educational concept.

PMID- 10068840
TI  - Glycoprotein IIb/IIIa platelet receptor blockers: are they ready for prime time
      in patients with unstable coronary artery disease?

PMID- 10068841
TI  - Early repolarization.
AB  - Early repolarization (ER) is an enigma. The purpose of this review is to
      reemphasize the overall electrocardiographic (ECG) pattern of this normal ST
      variant which continues to challenge the clinician because of its similarity to
      the current of injury potential to myocardium or an acute pericarditis. The data
      were provided from the studies identified through computerized searches of
      Medline, Toxline, Oxford, Agricola, and Bios Afterdark, Cumulative index, and a
      review of bibliographies of relevant articles on the related subjects. Early
      repolarization has elevated, upward, concave ST segments, located commonly in
      precordial leads, with reciprocal depression in a VR, tall, peaked and slightly
      asymmetrical T waves with notch, and slur on the R wave. The other accompanying
      features in the ECG are vertical axis, shorter and depressed P-R interval, abrupt
      transition, counterclockwise rotation, presence of U waves, and sinus
      bradycardia. Males dominate and patients are often younger than 50 years of age.
      The incidence of 1 to 2% is found equally common in all races. Degree and
      incidence of ST elevation decrease as age advances. Exercise or isoproterenol
      administration may normalize the ST segment. Early repolarization is a benign
      condition. If the ECG conforms to a classical pattern of ER on serial ECGs, it
      would exclude the unnecessary hazards of present day revascularization therapy
      for myocardial infarction such as primary angioplasty or thrombolytic therapy, or
      aggressive management of acute pericarditis, and so forth. This review concludes
      with a discussion of comparative ECG features of ER, pericarditis, and myocardial
      infarction, and provides an algorithm for diagnostic management of patients
      suffering from these conditions.

PMID- 10068842
TI  - Assessing the appropriateness of coronary revascularization: the University of
      Maryland Revascularization Appropriateness Score (RAS) and its comparison to RAND
      expert panel ratings and American College of Cardiology/American Heart
      Association guidelines with regard to assigned appropriateness rating and ability
      to predict outcome.
AB  - BACKGROUND: Significant regional variation in procedural frequencies has led to
      the development of the RAND and American College of Cardiology/American Heart
      Association (ACC/AHA) guidelines; however, they may be difficult to apply in
      clinical practice. The University of Maryland Revascularization Appropriateness
      Score (RAS) was created to address the need for a simplified point scoring
      system. HYPOTHESIS: The study was undertaken to compare revascularization
      appropriateness ratings yielded by the RAND Expert Panel Ratings, ACC/AHA
      guidelines, and the University of Maryland RAS. METHODS: We applied these three
      revascularization appropriateness scoring systems to 153 catheterization
      laboratory patients with a variety of cardiac diagnoses and treatments. For each
      patient, appropriateness scores assigned by each of the three systems were
      compared with each other and with the actual treatment delivered. Concordance of
      care with appropriateness score was then correlated with outcome. RESULTS: There
      were significant differences among all three scoring systems in their ratings and
      in the concordance of treatment with appropriateness rating. When treatment
      provided was concordant with RAND ratings, there was a lower occurrence of
      subsequent coronary artery bypass grafting (CABG), the composite end point of
      either CABG or percutaneous transluminal coronary angioplasty (PTCA), and the
      composite end point of death, myocardial infarction (MI), or revascularization.
      When treatment was concordant with the ACC/AHA guidelines, there was lower
      occurrence of all-cause mortality, PTCA, the composite end point of either CABG
      or PTCA, and the composite end point of death, MI, or revascularization. When
      treatment provided was concordant with the RAS, there was lower occurrence of
      cardiac death, all-cause death, CABG, the composite end point of either CABG or
      PTCA, and the composite end point of death, MI, or revascularization.
      CONCLUSIONS: The RAS is a simple scoring system to assess revascularization
      appropriateness. When the RAND, ACC/AHA, and RAS systems are compared in a
      catheterization laboratory population, they rate the same patient differently and
      vary in their correlation of appropriateness rating with outcome.

PMID- 10068843
TI  - An electrocardiographic algorithm for the prediction of the culprit lesion site
      in acute anterior myocardial infarction.
AB  - BACKGROUND: Although the 12-lead electrocardiogram (ECG) has been found useful in
      identifying the left anterior descending (LAD) coronary artery as the infarct
      related artery in acute myocardial infarction (MI), it has traditionally been
      felt to be incapable of localizing the culprit lesion within the LAD itself. Such
      a capability would be important, because anterior MI due to proximal LAD lesions
      carry a much worse prognosis than those due to more distal or branch vessel
      lesions. HYPOTHESIS: This study investigated whether certain ECG variables-
      especially an ST-segment injury pattern in leads aVL and/or V1--would correlate
      with culprit lesion site, and an ECG algorithm was developed to predict culprit
      lesion site. METHODS: The initial ECGs of 55 patients who had undergone cardiac
      catheterization after an anterior or lateral MI were reviewed to identify the
      leads with an ST-segment injury pattern; the corresponding catheterization films
      were then reviewed to identify the location of the culprit lesion; and these
      separate findings were then compared. RESULTS: The sensitivity and specificity of
      an ST-injury pattern in aVL in predicting a culprit lesion before the first
      diagonal branch were 91 and 90%, respectively; the same values in predicting a
      lesion prior to the first septal branch were 85 and 78%. ST-segment elevation in
      V1, on the other hand, was a much less sensitive and specific predictor of a
      preseptal lesion. Overall, our algorithm correctly identified the culprit lesion
      location in 82% of our patients. CONCLUSION: Based on our findings, we conclude
      that a ST-segment injury pattern in aVL during an anterior myocardial infarction
      predominantly reflects a proximal LAD lesion and therefore constitutes a high
      risk finding.

PMID- 10068844
TI  - Lack of association between prior infection with Chlamydia pneumoniae and acute
      or chronic coronary artery disease.
AB  - BACKGROUND: Higher than normal serologic titers and the detection of bacteria
      within atheroma have suggested an association between Chlamydia pneumoniae (C.
      pneumoniae) infection and coronary heart disease (CHD), but the relationship has
      not been well established. HYPOTHESIS: The study was designed to establish a lack
      of relationship between chronic C. pneumoniae infection and CHD. METHODS:
      Chlamydia-specific IgG-antibody was assayed using an indirect immunofluorescence
      test in the serum of 159 patients with severe arterial disease and 203 patients
      with a heart valve prostheses and no demonstrable CHD. Fatal and nonfatal
      vascular events and systemic thromboembolism were recorded over a 2-year period.
      RESULTS: In the arterial group 107 patients (67.3%) and in the valvular group
      120/203 (59.1%) were positive for C. pneumoniae antibody. The number of patients
      with fatal or nonfatal vascular events (double end point) in the arterial and
      valvular groups was 23 and 2, respectively (p < .0001). Triple end points (fatal
      plus nonfatal vascular events plus thromboembolism) were also more frequent in
      the arterial group (p < 0.002). The prevalence of chlamydia antibody positivity
      was the same in the arterial and valvular groups, and the occurrence of clinical
      events was also the same for chlamydia-positive (227 patients) as for chlamydia
      negative (135 patients). After adjustment for confounding variables, only
      arterial disease was a predictive factor for double (OR 17.0; 95% CI 3.94-73.3)
      or triple (OR 3.12; 95% CI 1.56-6.25) end points. CONCLUSION: We find C.
      pneumoniae chronic infection not to be an independent risk factor for acute or
      chronic arterial disease.

PMID- 10068845
TI  - Early mitral regurgitation after acute myocardial infarction does not contribute
      to subsequent left ventricular remodeling.
AB  - BACKGROUND: It is well known that mitral regurgitation may lead to left
      ventricular dilation; however, the relationship between progressive left
      ventricular dilation after acute myocardial infarction (MI) and mitral
      regurgitation has not yet been clarified. HYPOTHESIS: This study tested the
      hypothesis that early mitral regurgitation contributes to left ventricular
      remodeling after acute MI. METHODS: We prospectively evaluated 131 consecutive
      patients by serial two-dimensional and Doppler echocardiography on Days 1, 2, 3,
      and 7, after 3 and 6 weeks, 3 and 6 months, and 1 year following acute MI.
      Patients were divided into two groups: those with mitral regurgitation in the
      first week after acute MI (Group 1, n = 34) and those without mitral
      regurgitation (Group 2, n = 81). RESULTS: Over 1 year, a significant increase in
      end-diastolic volume index (from 62.1 +/- 12.9 to 70.5 +/- 23.6 ml/m2, p = 0.001)
      with a strong linear trend (F = 15.1, p < 0.001) was noted. Initial end-diastolic
      volume index was higher in Group 1 (65.6 +/- 13.3 vs. 60.4 +/- 12.5 ml/m2, p =
      0.047), but this difference remained constant throughout the study (F = 1.76, p =
      NS). Therefore, the pattern of end-diastolic volume changes was similar in both
      groups during the period of observation. CONCLUSIONS: These data indicate that
      early mitral regurgitation after acute MI does not contribute to subsequent left
      ventricular remodeling in the first year after myocardial infarction.

PMID- 10068846
TI  - Effects of digoxin on electrocardiogram in patients with acute atrial
      fibrillation--a randomized, placebo-controlled study. Digitalis in Acute Atrial
      Fibrillation (DAAF) Trial Group.
AB  - BACKGROUND: Studies of healthy volunteers or patients in sinus rhythm have
      indicated that treatment with digoxin produces characteristic changes in the
      electrocardiogram (ECG). No randomized, placebo-controlled studies are available
      and no study has investigated the effect on ECG in patients with atrial
      fibrillation. HYPOTHESIS: In a substudy to a trial comparing the therapeutic
      effect of intravenously administered digoxin with placebo in patients with acute
      atrial fibrillation, we investigated these effects as well as the relation
      between ECG changes and serum concentration of digoxin. METHODS: In all, 167
      patients were included. Standard ECGs recorded at baseline, and at 2, 6, 12, and
      16 h after randomization were digitized, and changes in RR-intervals, QRS width,
      ST-segment amplitude at 60 ms after the J point, T-wave amplitude, and QTc
      interval were calculated. Furthermore, the correlation between the serum
      concentration of digoxin at 16 h after inclusion and changes on the ECG was
      analyzed. RESULTS: Compared with placebo, digoxin resulted in an increase in RR
      interval (p < 0.0001), a decrease in ST-segment and T-wave amplitude (p = 0.009
      and p = 0.002, respectively), and in the QTc interval (p = 0.01). These changes
      were present 2 h after the first dose, but were more pronounced after 16 h. There
      was no significant correlation between serum concentration of digoxin and ECG
      changes at 16 h. CONCLUSION: Compared with placebo, digoxin produces significant
      changes on ECG in patients with acute atrial fibrillation. The changes are in
      accordance with previous findings in individuals in sinus rhythm. There was no
      correlation between serum concentration of digoxin and ECG changes.

PMID- 10068847
TI  - Circadian variations of QTc dispersion: is it a clue to morning increase of
      sudden cardiac death?
AB  - BACKGROUND: Several studies related to cardiac events including sudden death have
      shown a peak incidence in the early morning hours. It has also been known that
      acute ischemia is a potent stimulus to increased dispersion of repolarization and
      development of malignant arrhythmias. HYPOTHESIS: The purpose of the present
      study was to investigate diurnal variations of corrected QT dispersion (QTcD) in
      patients with coronary artery disease (CAD) (Group 1) compared with controls with
      normal coronary angiograms (Group 2). METHODS: We investigated a total of 110
      patients who had been referred for coronary angiography, of whom 62 (42 men, 20
      women; age 55 +/- 7 years) had double- or triple-vessel disease, and of whom 48
      (31 men, 17 women; age 54 +/- 9 years) had normal coronary angiograms. QTcD
      measurements were calculated from a 12-lead resting electrocardiogram (ECG)
      during sinus rhythm. These ECGs were obtained for each patient in the morning, at
      noon, in the evening, and at night on the day after performance of coronary
      angiography. QTcD was significantly greater in patients with abnormal coronary
      angiograms (Group 1) than in patients with angiographically documented normal
      coronary arteries (Group 2). This difference appeared to be more prominent in the
      morning hours (p < 0.001) than at other times. QTcD in the evening and night
      hours was not statistically different (p > 0.05) between both groups. We also
      compared intragroup QTcD values: QTcD values were significantly increased in the
      morning hours and were more prominent in Group 1 than in Group 2. CONCLUSIONS:
      Our data suggest that QTcD has a circadian variation with an increase in the
      morning hours, especially in patients with coronary artery disease. This finding
      was thought to be an explanation for the role played by sympathetic nervous
      system in the occurrence of acute cardiac events and sudden death during these
      hours.

PMID- 10068848
TI  - Effect of aprindine on heart rate variability indices in patients with ischemic
      heart disease.
AB  - BACKGROUND: Decreased heart rate variability indices (HRV) are associated with
      untoward outcome of patients with ischemic heart disease (IHD). Most class I
      antiarrhythmic agents decrease HRV, but aprindine (a new class I antiarrhythmic
      agent) is reported to increase HRV in patients without ischemia. HYPOTHESIS: The
      study was undertaken to determine whether apridine might increase HRV in patients
      with IHD. METHODS: To investigate the effect of aprindine on HRV in patients with
      IHD, we performed 24-h ambulatory electrocardiogram (ECG) at the end of placebo
      and aprindine (60 mg daily) treatment phases on 38 patients with IHD and at least
      isolated premature ventricular contractions (PVC). The study protocol utilized a
      single blind, 4-week, placebo-controlled design. Heart rate variability from
      ambulatory ECG included SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%);
      frequency analysis of HRV consisting of total (ms, 0.01-1.00 Hz), low (ms, 0.04
      0.15 Hz), and high (ms, 0.15-0.40 Hz) components. RESULTS: Study patients were
      divided into three groups according to the severity of IHD and antiarrhythmic
      efficacy of aprindine. Group 1 consisted of 15 patients with angina with single
      vessel disease, and Group 2 was composed of 10 patients with either multivessel
      disease or post myocardial infarction; PVCs decreased in both groups as result of
      aprindine treatment. Group 3 consisted of 13 patients who showed no decreased PVC
      after aprindine treatment. RMSSD increased, and pNN50 and high-frequency spectra
      tended to increase in Group 1, while SD, rMSSD, pNN50, and total and low
      frequency spectra decreased in Group 3; no significant changes were observed in
      Group 2. Aprindine significantly augments vagal activity, as reflected by the
      increase of rMSSD, pNN50, and high-frequency spectra in mild IHD. CONCLUSION:
      These salutary effects are less in more severe IHD, but aprindine does not
      aggravate HRV. Thus, if there are salutary effects on arrhythmias and no
      proarrhythmic effects, aprindine could be prescribed to patients with IHD without
      concern about decreasing HRV.

PMID- 10068849
TI  - Differential hormonal profiles of adrenomedullin and proadrenomedullin N-terminal
      20 peptide in patients with heart failure and effect of treatment on their plasma
      levels.
AB  - BACKGROUND: Adrenomedullin (AM) is a potent vasodilatory peptide discovered in
      human pheochromocytoma tissue. Proadrenomedullin N-terminal 20 peptide (PAMP)
      processed from an AM precursor is also a novel hypotensive peptide which inhibits
      catecholamine secretion from sympathetic nerve endings. HYPOTHESIS: The present
      study sought to examine the relationships between the two peptides and other
      clinical parameters by measuring the plasma AM and PAMP concentrations in 98
      patients with heart failure. METHODS: In all, 98 patients [65 men and 33 women,
      aged 58.2 +/- 11.0 years, mean +/- standard deviation (SD)] with heart failure
      and 26 healthy volunteers (12 men and 14 women, aged 54.1 +/- 8.6 years) were
      examined in this study. Heart failure was secondary to previous myocardial
      infarction in 58 patients, valvular disease in 28, cardiomyopathy in 9, and
      congenital heart disease in 3. All patients were classified into two groups of
      class I or II (Group 1) and class III or IV (Group 2) according to the New York
      Heart Association (NYHA) functional classification. RESULTS: Both plasma AM and
      PAMP concentrations in the patients were significantly higher than those in
      healthy volunteers. In addition, plasma AM and PAMP concentrations in patients in
      class III or IV of New York Heart Association (NYHA) classification were
      significantly higher than those in NYHA class I or II. The elevated plasma
      concentrations of these peptides in patients in NYHA class III or IV
      significantly decreased in response to the treatment for 7 days. There was a
      significant correlation between plasma AM and PAMP, though the plasma
      concentration of PAMP was one-fifth to one-seventh of that of AM in patients and
      controls. The plasma AM concentration correlated significantly with the plasma
      concentrations of atrial and brain natriuretic peptides, epinephrine, and right
      atrial pressure, whereas such a relationship was not noted for the plasma PAMP
      concentration. CONCLUSIONS: Judging from the difference in not only the
      biological actions but also the hormonal profiles between AM and PAMP, they may
      differentially modulate the cardiovascular system in patients with heart failure,
      although they are processed from the same precursor.

PMID- 10068850
TI  - Isolated left ventricular abnormal trabeculation in adults is associated with
      neuromuscular disorders.
AB  - BACKGROUND: Isolated left ventricular abnormal trabeculation (ILVAT) is defined
      as > 3 coarse trabeculations of the left ventricular wall, apically to the
      papillary muscles, in hearts without congenital malformations. HYPOTHESIS: The
      aims of the study were to assess by echocardiography the prevalence of ILVAT, to
      confirm the diagnosis by cardiac magnetic resonance imaging (CMRI), to look for
      cardiac findings in ILVAT, and to determine whether ILVAT is familial and
      associated with neurological disorders. METHODS: During a 1-year period (July
      1995 to July 1996) all patients in whom transthoracic echocardiography visualized
      ILVAT, were included in the study. The examination and measurements were
      performed according to established guidelines. RESULTS: During 1 year, ILVAT was
      found in 6 of 3,397 patients (0.2%). When applied, CMRI confirmed ILVAT. Four
      patients had heart failure, all had electrocardiographic (ECG) abnormalities.
      None of the investigated relatives showed ILVAT. One patient had Becker's
      muscular dystrophy, three had mitochondrial myopathy, one had polyneuropathy, and
      one had muscle wasting of unknown origin. CONCLUSIONS: Isolated left ventricular
      abnormal trabeculation is rare, visible on echocardiography and CMRI, associated
      with ECG abnormalities, sometimes with heart failure, and always with
      neuromuscular disorders. Thus, when ILVAT is found, the cardiologist should
      consider a neurology referral.

PMID- 10068851
TI  - Deceleration-dependent shortening of the QT interval: a new electrocardiographic
      phenomenon?
AB  - In clinical cardiology, deceleration-dependent QT interval shortening is
      considered to be an extraordinary electrocardiographic phenomenon. We present an
      early premature born 4-year-old African-American girl with complications related
      to her premature birth, developmental delay, and several episodes of cardiac
      arrest. An episode of severe transient bradyarrhythmia was documented on Holter
      monitoring. The unique feature of the rhythm strips was paradoxical gradual
      shortening of the QT interval to 216 ms with accompanying transient T-waves
      abnormalities. The activation of the Ik, ACh due to an unusually high vagal
      discharge to the heart is proposed as a possible mechanism responsible for both
      slowing of the heart rate and shortening of the QT interval.

PMID- 10068852
TI  - Thrombosed pulmonary arterial aneurysm in Eisenmenger's syndrome.

PMID- 10068853
TI  - Bullet in the heart.

PMID- 10068854
TI  - Multiple coronary occlusions associated with ST-segment elevation.
AB  - We describe the case of a patient with rapid sequential ST-segment elevation in
      different areas on the electrocardiogram (ECG) associated with lesions of
      differing etiologies in the corresponding coronary arteries. Prior reports of ST
      segment elevations in multiple areas on the ECG have been from obstructions of
      single coronary vessels whose distribution overlapped separate areas on the ECG
      or spasm of multiple coronary arteries. We could find no prior reports of such
      rapid sequential ST-elevation in different areas on the ECG caused by two
      differing etiologies.

PMID- 10068855
TI  - Myotonic dystrophy associated with QT prolongation and torsade de pointes.
AB  - A rare case of myotonic dystrophy (MD) with congestive heart failure, associated
      with QT prolongation and torsade de pointes (TdP) is reported. A 53-year-old
      woman was admitted to the hospital because of congestive heart failure.
      Electrocardiograph (ECG) showed first-degree atrioventricular block and QT
      prolongation. During hospitalization, TdP appeared but returned to sinus rhythm
      spontaneously. As the patient had quadriplegia, a myopathic face, cataracts,
      diabetes mellitus, and an increased number of cytosine-thymineguanine (CTG)
      repeats (760 repeats), she was diagnosed as having MD. Electrocardiographic
      analysis of her family also revealed abnormal QT(U) prolongation in her daughter
      and brother who both had MD, while ECG findings of other family members without
      MD were normal. Thus, the presence of QT(U) prolongation was associated with MD
      in this family.

PMID- 10068856
TI  - Potential proarrhythmic effects of implantable cardioverter-defibrillators.
AB  - Implantable cardioverter-defibrillator (ICD) interventions have the potential to
      be proarrhythmogenic. New arrhythmias can occur in the setting of clinically
      appropriate therapies, as well as during a cardiac rhythm for which therapy is
      not intended. Cardioversion/defibrillation therapies, antitachycardia pacing, and
      antibradycardia pacing are potential triggers for the development of new
      arrhythmias. Newer ICDs allow better recognition and interpretation of the
      arrhythmias that are induced by delivered therapies. Two cases of ICD-induced
      proarrhythmias are described. Based on the course of these patients and review of
      previous reports, proarrhythmic effects of ICD interventions along with
      prevention and management strategies are discussed.

PMID- 10068857
TI  - Coronary stent deployment in a young adult with Kawasaki disease and recurrent
      myocardial infarction.
AB  - A 19-year-old man developed a huge coronary aneurysm and stenosis in the right
      coronary artery as a sequela of Kawasaki disease (KD) that resulted in recurrent
      episodes of myocardial infarction. Coronary ischemic events were successfully
      prevented after balloon angioplasty followed by coronary stent implantation into
      the stenotic lesion. The stent deployment may have an advantage compared with
      balloon angioplasty and other new devices for the treatment for patients with KD
      showing stenotic lesions without dense calcification.

PMID- 10068858
TI  - Thrombolysis of mobile right atrial thrombi following severe pulmonary embolism.
AB  - Thrombolysis may favorably affect the clinical outcome of mobile right atrial
      thrombus following pulmonary embolism (PE). We report the case of three patients
      with mobile right atrial thrombus following PE, in whom fibrinolysis was
      performed. Atrial mass disappeared on the control echocardiogram, but control
      ventilation perfusion scan showed new perfusion defects in all patients.
      Thrombolysis seems successful for the treatment of patients with mobile right
      atrial thrombus following PE; however, recurrent PE may be induced by
      fibrinolysis. This may affect the benefit of such therapy and should be taken
      into account when using this therapeutic treatment.

PMID- 10068859
TI  - Aubrey Leatham: twentieth century pioneer in auscultation.

PMID- 10068860
TI  - Clinical characteristics of ruptured chordae tendinae in hospitalized patients:
      primary tear versus infective endocarditis.

PMID- 10068861
TI  - Pulmonary embolism and impending paradoxical embolism: a role for transesophageal
      echocardiography?

PMID- 10068862
TI  - Pulsed tissue Doppler evaluation of mitral annulus motion: a new window to
      assessment of diastolic function.
AB  - Diastolic dysfunction is an important cause of cardiac heart failure. To date
      detailed assessment of diastolic left ventricular (LV) function has required
      invasive methods which are impractical in the clinical routine. The prevailing
      non-invasive method has been Doppler echocardiography with use of mitral inflow
      and pulmonary vein inflow parameters, measurements providing no direct assessment
      of either ventricular relaxation or compliance, and influenced by multiple
      haemodynamic factors. We sought to determine the tissue Doppler pattern from the
      mitral annulus motion in normals and in patients with expected LV-diastolic
      dysfunction. Using pulsed tissue Doppler we recorded peak velocities from the
      mitral annulus motion in 16 young normals, 10 older normals and in two groups of
      patients expected to have an LV-diastolic relaxation abnormality, i.e. 15
      patients with systemic hypertension and 10 patients with significant aortic
      stenosis. The peak early diastolic (E) annulus velocity was significantly (P <
      0.001) lower in older normals compared with young, and the late diastolic
      velocity (A) was higher (P < 0.01). Compared with the older normals, patients
      showed significantly lower E-velocities (P < 0.05 hypertensive patients), more
      pronounced in the patients with aortic stenosis (P < 0.001), but the A-velocities
      were not higher. In systole a decrease in peak velocity was noted with increasing
      age and in patients with aortic stenosis. In conclusion, pulsed tissue Doppler
      measurement of annulus motion seems to provide valuable and easily obtainable
      information about LV-diastolic function, and furthermore there is striking change
      in velocity pattern with increasing age which necessitates age-matched reference
      values.

PMID- 10068863
TI  - Properties of spiral waves in a piece of isotropic myocardium.
AB  - Tachyarrhythmias of the heart can be due to the presence of one or more spiral
      waves of electrical activity. Spiral waves were simulated using a previously
      described ionic model of cardiac action potentials in a 75 x 75 network of
      compartments. The compartments were connected by means of resistors and made
      isotropic in order to catch basic properties of spiral waves. The cross-field
      stimulation technique was used to generate single or double spiral waves. The
      analysis showed that a spiral wave was created when the second excitation front
      became critically curved, in the wake of the preceding wave, so that decremental
      propagation occurred. A spiral wave could also be generated from a wave
      circulating around an obstacle when the obstacle size was suddenly reduced. The
      spiral waves steadily circled around an area with excitable but unexcited cells.
      An undisturbed spiral wave in the isotropic medium circled around in a stable
      pathway, but drifted along the borders of cells made non-excitable. An excitation
      within an existing spiral wave could generate new spiral waves that interacted
      with each other and formed complex excitation patterns. A sudden prolongation of
      the refractory period reduced the central area with unexcited cells in the spiral
      pathway but only slightly prolonged the revolution time. A further prolongation
      of the refractory period extinguished the spiral wave when the tip of the spiral
      wave invaded refractory areas. The described ionic compartment model could
      accurately produce spiral waves with properties in line with experimental results
      reported by others.

PMID- 10068864
TI  - Renal prostanoids: physiological relevance in healthy salt-depleted women.
AB  - The effective role played by prostanoids in the control of renal function has
      been investigated in healthy women with salt depletion. Salt depletion (SD2
      group, n = 6) was induced by low sodium chloride dietary intake (< or = 60 mmol
      per day) and combined treatment with natriuretic and potassium-sparing drugs. At
      the end of the depletive treatment, the cumulative sodium deficit was 513 +/- 56
      mmol. The renal function and urinary excretions of prostaglandin (PG) E2, 6-keto
      PGF1 alpha (6KPGF) and thromboxane (Tx) B2 were evaluated during hypotonic
      polyuria. The basal values of plasma sodium and potassium concentrations, plasma
      renin activity (PRA) and urinary aldosterone excretion were determined before the
      induction of hypotonic polyuria. Paired studies were performed in the absence
      (control) and presence of indomethacin both in the SD2 group and in a previously
      studied group (N2, n = 6) of healthy women in normal sodium and potassium
      balance. Women in normal balance received 100 mg i.m. of indomethacin, salt
      depleted women received only 50 mg (because 100 mg of the drug produced a
      prolonged anuria). In the SD2 vs. N2 group in the absence of treatment the
      following significant differences were found: (a) higher basal values of PRA and
      urinary aldosterone excretion; (b) higher urinary excretions of 6KPGF and TxB2
      but not of PGE2; (c) lower values of urinary flow rate, creatinine clearance,
      absolute and fractional excretions of sodium and chloride, plasma osmolality and
      plasma electrolyte concentrations. The effects of the indomethacin have been
      assessed as percentage variations by using paired data for each experimental
      group. In the SD2 vs. N2 group the reduction in urinary excretions of 6KPGF, TxB2
      and potassium as well as in creatinine clearance were not significantly
      different. On the other hand, the following were significantly different: (a) the
      lower reduction in PGE2 excretion; (b) the higher reduction in urinary flow rate
      and in CH2O; (c) the reductions in absolute and fractional excretions of sodium
      and chloride, and the increase in plasma potassium concentration, significant in
      the SD2 group but not in the N2 group. The data suggest that: (1) when stimulated
      by salt depletion the renal biosynthetic pathways of PGI2 and TxA2 showed greater
      sensitivity to indomethacin inhibition; (2) the effects of the neurohormonal
      systems activated by salt depletion were either modulated or mediated by renal
      prostanoids.

PMID- 10068865
TI  - Controlled oral glucose tolerance test: evaluation of insulin resistance with an
      insulin infusion algorithm that forces the OGTT glycaemic curve within the normal
      range. A feasibility study.
AB  - This is a technical study to show the feasibility of a computer-controlled oral
      glucose tolerance test (OGTT) using a specific algorithm, consisting of an OGTT
      carried out while insulin is infused as required to keep glycaemia within the
      normal range (National Diabetes Data Group 1979 criteria). This technique allows
      (a) the amount of insulin (insulin area) required to maintain a normal glycaemic
      curve to be assessed, a parameter indicating the degree of insulin resistance;
      and (b) the unique parameter consisting of the insulin secretory response (C
      peptide) to a normal glycaemic curve under the inhibitory feedback exerted by the
      insulin levels required to maintain normal glycaemia to be obtained. Preliminary
      results confirmed the feasibility of this approach by showing that during the
      test while the glycaemic area was kept normal the insulinaemic area (endogenous +
      infused insulin) increased markedly in obese (n = 8) and obese diabetic (n = 5)
      subjects compared with normal subjects (n = 6), with values of 145.10 +/- 26.71,
      204.75 +/- 20.77 and 68.25 +/- 5.93 nmol l-1 min-1 respectively (P < 0.01 in both
      instances). In contrast, endogenous insulin secretion (C-peptide levels) remained
      almost unchanged. Compared with data in normal subjects, free fatty acid (FFA)
      values were basally elevated in the obese and obese diabetic patients, and
      underwent a smaller decrease during the test. The FFA areas were greater than
      normal in both groups of patients, suggesting that FFAs were not fully
      suppressible despite the highest possible insulin levels (higher insulin levels
      would produce hypoglycaemia). The computer-controlled OGTT might be useful for
      the metabolic study of patients in the clinical setting.

PMID- 10068866
TI  - How can the variability in ultrasound measurement of intima-media thickness be
      reduced? Studies of interobserver variability in carotid and femoral arteries.
AB  - A critical component in scientific studies of most biological variables is the
      variation or error in measurements which leads to non-identical results of
      repeated measurements from the same subject. The aim of this study was to
      investigate whether the interobserver error (s) in measurement of intima-media
      thickness (IMT) in carotid and femoral arteries could be decreased if the mean
      value obtained using two ultrasound images from each of the right and left
      arteries was used in the analyses instead of the mean value obtained using images
      from only the right artery. In addition, we wished to evaluate two different
      reading procedures, one based on manual tracing of echo interfaces and the other
      on automated edge detection. In a methodological study, 50 subjects were examined
      with ultrasound twice in the same day by two independent laboratory
      technologists. The ultrasound images were analysed in two ways: using a
      computerized manual tracing analysing system and an automated analysing system.
      When both right and left carotid arteries were examined (manual reading), the
      interobserver error was smaller than that determined for the examination of only
      the right artery, for IMTmean in both the common carotid artery (P = 0.06) and
      the carotid artery bulb (P < 0.05). The interobserver error was also
      significantly smaller for double-sided vs. one-sided examination with automated
      reading of IMTmean in the common carotid artery (P < 0.01) and in the carotid
      artery bulb (P < 0.01). The coefficient of variation (CV) for measurement in the
      common carotid artery decreased from 8.6% (one-sided, manual reading) to 5.3%
      (double-sided, automated reading). The interobserver error in measurement of IMT
      in the common femoral artery did not improve by examination of both right and
      left arteries. The results from this study show that the interobserver errors in
      measurement of IMT can be decreased by using ultrasound images from both the
      right and the left carotid arteries, and that the use of an automated analysing
      system greatly simplifies the reading of ultrasound images with sustained low
      variability.

PMID- 10068867
TI  - Non-linear cardiac dynamics and morning dip: an unsound circadian rhythm.
AB  - The frequency of sudden cardiac death increases in the morning. The relationship
      between decreased complexity of heart rate dynamics and sudden cardiac death has
      been documented. An understanding of circadian variation in the complexity of
      cardiac dynamics may be important to predict and prevent sudden cardiac death.
      Dynamic 24-h electrocardiographic recordings were obtained from 30 healthy
      ambulant subjects aged 41-50 years, and the digitized data were partitioned into
      sections of 30 min duration. For each section, four indexes obtained from
      separate algorithms of non-linear dynamics of the RR interval--modified
      correlation dimension, Lyapunov exponent, approximate entropy, and fractal
      dimension--were calculated. Normalized low-(0.04-0.15 hertz) and high-frequency
      (> 0.15 hertz) components were also calculated. All four indexes of non-linear
      dynamics showed a remarkably similar circadian rhythm: a prominent morning dip
      preceded by a steep decline during the late night, a recovery during the evening
      and a peak around midnight. In the morning, the low-frequency component rose
      rapidly with concomitant reduction in the high-frequency component. The
      complexity of cardiac dynamics decreases significantly in the morning, and this
      may contribute to the ominously increased rate of cardiac death in the morning
      hours.

PMID- 10068868
TI  - C-type natriuretic peptide does not affect plasma and urinary adrenomedullin in
      man.
AB  - To investigate whether C-type natriuretic peptide (CNP) at pathophysiological
      plasma levels stimulates the release of adrenomedullin (ADM) in man, six healthy
      subjects (three men and three women, mean age 35 +/- 3 years, range 33-40 years)
      received an intravenous infusion of synthetic human CNP-22 (2 pmol kg-1 min for 2
      h), in a single-blind, placebo-controlled, random order, cross-over study, with
      measurements of the plasma levels of cyclic guanosine monophosphate (cGMP), ADM,
      renin and atrial natriuretic peptide (ANP), arterial pressure, heart rate, renal
      blood flow (para-aminohippurate clearance), glomerular filtration rate
      (creatinine clearance), and the urinary excretion rates of cGMP, ADM and sodium.
      Infusion of CNP induced increases in its own levels (from 1.17 +/- 0.11 up to
      21.13 +/- 1.41 pmol l-1) without modifying the plasma levels of cGMP, ADM, renin
      and ANP, the urinary excretion rate of ADM and cGMP, renal haemodynamics and
      sodium excretion. These data indicate that circulating CNP is not involved in the
      regulation of ADM release, renal haemodynamics and sodium excretion in man.

PMID- 10068869
TI  - Myocardial sestamibi uptake in healthy subjects is related to age, gender and
      habitus.
AB  - The object of this study was to evaluate the effect of gender, age and
      anthropometric data on regional isotope uptake in myocardial perfusion
      scintigraphy using 99mTc-MIBI-SPECT (myocardial sestamibi single-photon emission
      technique). Seventy-one healthy, non-smoking subjects, 42 men and 29 women
      between 40 and 80 years of age, with less than 5% likelihood of having coronary
      artery disease were studied. All subjects underwent a maximal exercise and rest
      MIBI-SPECT using a 2-day protocol and a 180 degrees anterior circular rotation.
      No correction for scatter or attenuation was made. Normalized regional activity
      was different in men and women in the anterior and inferior regions, with higher
      values anteriorly in men and inferiorly in women. Regional activity also differed
      with age in both women and men with higher relative activity in the anterior
      regions in the oldest age groups. Higher activities were seen in the basal parts
      of the left ventricle at rest compared with stress in both men and women.
      Regional isotope uptake was significantly affected by habitus expressed as body
      mass index (BMI) and thoracic circumference. Different protocols for stress and
      rest seem to be needed for men and women in different age groups, and for stress
      and rest when performing semiquantitative MIBI-SPECT and comparing data with a
      normal file of healthy subjects. Furthermore, such anthropometric data as BMI
      and/or thoracic circumference should be considered in order to minimize the risk
      for false-positive or false-negative scintigraphic results.

PMID- 10068870
TI  - Accuracy of a novel real-time microprocessor QRS detector for heart rate
      variability assessment.
AB  - Assessment of heart rate variability from 24-h recordings requires a high-quality
      Holter, expensive equipment and multistage processing of recordings. We compared
      a new personal computer-based digital QRS detector system with a Holter recorder,
      and found the two methods to be equally accurate in time and frequency domain
      measures of heart rate variability.

PMID- 10068871
TI  - Standardized intermittent static exercise increases peritendinous blood flow in
      human leg.
AB  - Alteration in tendinous and peritendinous blood flow during and after exercise is
      suggested to contribute to the development of Achilles tendon injury and
      inflammation. In the present study a method for evaluating the influence of
      standardized workload on peritendinous flow is presented. The radioactive isotope
      xenon-133 was injected just ventrally to the Achilles tendon 5 cm proximal to the
      tendon's insertion on the calcaneous. The disappearance of 133Xe was used to
      determine blood flow during intermittent static exercise of the calf muscle (1.5
      s exercise/1.5 s rest) for 30 min at a workload equivalent to individual body
      weight (1 BW) in six healthy volunteers around both Achilles tendons (n = 12).
      During intermittent static exercise, blood flow was increased from 1.8 +/- 0.3 ml
      100 g tissue-1 min-1 (mean value and SEM) (rest) to 6.1 +/- 1.3 ml 100 g tissue-1
      min-1 (exercise) (P < 0.05). The exercise induced an average increase in blood
      flow (3.4-fold) equivalent to results previously obtained during regular dynamic
      heel raises (P > 0.05). It is concluded that the method is well suited to study
      the influence of standardized workload on the physiology and pathophysiology of
      the tissue around the Achilles tendon in humans.

PMID- 10068872
TI  - Paris medicine: perspectives past and present.

PMID- 10068873
TI  - Before the clinic: French medical teaching in the eighteenth century.

PMID- 10068874
TI  - Was anatomical and tissue pathology a product of the Paris clinical school or
      not?

PMID- 10068875
TI  - Pious pathology: J. L. Alibert's iconography of disease.

PMID- 10068876
TI  - Corvisart and Broussais: human individuality and medical dominance.

PMID- 10068877
TI  - Laennec and Broussais: the 'sympathetic' duel.

PMID- 10068878
TI  - Dichotomy or integration? Medical microscopy and the Paris clinical tradition.

PMID- 10068879
TI  - 'Faithful to its old traditions'? Paris clinical medicine from the second empire
      to the Third Republic (1848-1872).

PMID- 10068880
TI  - Paradigm lost or paradise declining? American physicians and the 'dead end' of
      the Paris clinical school.

PMID- 10068881
TI  - Cervical cytology and colposcopy in young patients attending genitourinary
      medicine clinics: invalid intrusion or preventive opportunity and definitive
      audit?

PMID- 10068882
TI  - Human papillomavirus (HPV) typing as an adjunct to cervical cancer screening.

PMID- 10068883
TI  - Inadequate cervical smears: results of an educational slide exchange scheme.
      Trent Gynaecological Pathology Quality Assurance Group.
AB  - Fifty-six slides, predominantly inadequate and of varying difficulty, were
      circulated to 12 laboratories as an educationally based slide exchange scheme.
      Three slides failed to achieve an agreed majority consensus opinion. Seventy
      percent of participants agreed with the consensus opinion in 80% of slides. Of
      the slides originally reported as inadequate, the consensus diagnosis was
      inadequate in 78%, negative in 12% and abnormal in 10%. The latter included two
      cases of high-grade dyskaryosis. There was good agreement for the two most
      frequent causes of inadequacy in submitted slides (obscured and poor
      cellularity). There was poor consistency in reporting the presence or absence of
      endocervical and immature squamous metaplastic cells, to an extent that questions
      their use in the assessment of smear adequacy. Three inadequate slides on
      consensus opinion were associated with subsequent cervical intraepithelial
      neoplasia (grade III) or invasive squamous cell carcinoma. In the latter case,
      the slide had originally been reported as negative by the submitting laboratory.

PMID- 10068884
TI  - Diagnosis of fibromatosis colli by fine needle aspiration (FNA) cytology.
AB  - This study presents eight cases of fibromatosis colli accurately diagnosed by FNA
      cytology. Fibromatosis colli is a rare fibroblastic lesion that manifests in the
      sternocleidomastoid muscle during the first to second months after birth. The
      tumours varied in size from 1 to 3 cm and engaged the lower, middle as well as
      the upper part of the sternocleidomastoid muscle. The FNA cytology smears showed
      mostly mature fibroblasts in a background of pink granular material and fragments
      of striated muscle fibres with degeneration. The cytological presentation
      together with the typical clinical setting will allow a definitive and accurate
      diagnosis, avoiding surgery.

PMID- 10068885
TI  - Argyrophilic nucleolar organizer region (AgNOR) technique: a helpful tool for
      differential diagnosis in urinary cytology.
AB  - The aim of this study was to investigate whether the AgNOR technique could be
      helpful for the cytologic diagnosis of neoplastic and non-neoplastic urinary
      tract lesions. We analysed the AgNOR pattern in urinary cytology in samples from
      70 patients. In every case the average number of silver precipitations per
      nucleus was counted and the range between the minimum and maximum AgNOR value
      calculated. Furthermore we noted whether the AgNOR precipitations had a
      homogeneous or heterogeneous distribution. The diseases were classified in three
      groups: non-neoplastic lesions, low grade and high grade carcinoma. Linear
      discriminant analysis (with jack-knife procedure) was performed with the AgNOR
      parameters as independent variables. The final diagnosis of each patient had been
      established by histological analysis of bladder biopsies. We obtained a correct
      classification in 84.3% of the cases. All patients with normal or reactive
      lesions were correctly classified and only two cases of low grade malignancy were
      erroneously diagnosed as non-malignant. Five high grade neoplasms had been
      classified as low grade and four low grade carcinomas had been over-diagnosed as
      high grade neoplasms. We conclude that a combined qualitative and quantitative
      AgNOR analysis can be useful in the differential diagnosis of urinary cytology.

PMID- 10068886
TI  - Heat shock protein (HSP)27: a further refinement in the diagnosis of suspicious
      fine needle aspirates of breast.
AB  - The technique of fine needle aspiration (FNA) is increasingly used in the
      investigation of breast abnormalities both palpable and impalpable. However, up
      to 20% of aspirates fall into two categories which require further investigation,
      because they either show cytological atypia or exhibit features which are
      suspicious of malignancy (reporting categories C3 and C4). The usefulness of the
      27-kD heat shock protein (HSP27) expression in refining these categories of
      suspicion, and possibly in predicting malignancy, was investigated using an
      established immunocytochemical staining procedure. Positive HSP27 staining was
      shown by 73.1% of C4 and 33.3% of C3 FNAs. Statistical analysis showed a
      significant difference between the results obtained for the C3 and C4 FNAs.

PMID- 10068887
TI  - Fine needle aspiration cytology of the breast using the Cytospin method.

PMID- 10068888
TI  - Fine needle aspiration (FNA) biopsy of primary cutaneous meningioma: report of
      two cases.
AB  - Two cases of primary cutaneous meningioma are described. A male and a female
      patient, aged 56 and 61 years, respectively, presented each with a solitary
      subepidermal nodule. The initial diagnosis was established in both patients by
      application of FNA biopsy. The subsequent histologic examination confirmed the
      cytologic diagnosis. Extensive investigation of the patients by computed
      tomography (CT) and nuclear magnetic resonance imaging (MRI) scans failed to
      reveal any primary meningioma of the neuraxis. Neurologic examination and routine
      laboratory test results were all normal. The microscopic features,
      immunocytological study and histology, which all gave a similar pattern to that
      seen in intracranial meningiomas, are discussed. Distinction from other cutaneous
      lesions that may be considered in the differential diagnosis is made. A brief
      review of the literature is also presented.

PMID- 10068889
TI  - Polymorphous low-grade adenocarcinoma of the soft palate: fine needle aspiration
      (FNA) cytology.

PMID- 10068890
TI  - Personal performance profiles: a useful adjunct to quality assurance in cervical
      cytology.

PMID- 10068891
TI  - Modified ultra fast Papanicolaou staining.

PMID- 10068892
TI  - Comparison between the intravenous and esophageal-gastric administration of
      glycerol in changing cochlear blood flow and serum osmolarity in the guinea pig.
AB  - The effects of glycerol on cochlear blood flow and serum osmotic pressure were
      studied in healthy guinea pigs. Laser Doppler flowmetry of cochlear blood flow
      after the esophageal-gastric administration of 50% glycerol demonstrated a
      greater increase in blood flow for a longer time than with the intravenous
      infusion of 50% glycerol. The intravenous infusion of glycerol did increase
      systemic blood pressure, which changed partially in parallel with the change in
      cochlear blood flow. The change in systemic blood pressure after esophageal
      gastric administration was slight. In another experiment designed to observe the
      changes in serum osmotic pressure after glycerol administration, the esophageal
      gastric route also caused a greater and longer increase in serum osmolarity than
      intravenous infusion. The increase in cochlear blood flow after glycerol
      administration was thought to be due to an increase in the osmotic gradient
      between the blood in the cochlear vessels and the interstitial fluid, or to the
      high osmolarity of the blood itself. The possible mechanisms underlying local
      blood flow increase caused by high serum osmolarity are discussed. Systemic blood
      pressure increase induced by glycerol could be an influential factor for the
      cochlear blood flow increase during intravenous infusion.

PMID- 10068893
TI  - Computed tomographic imaging to determine the frequency of anatomical variations
      in pneumatization of the ethmoid bone.
AB  - The present study was performed on axial and coronal CT scans of 212 patients.
      Scans were analyzed by an anatomist and a radiologist for the presence of
      Haller's cells, agger nasi cells, Onodi's cells and pneumatized crista galli.
      Results demonstrated the presence of Haller's cells in 21.2%, Onodi's cells in
      10.4% and pneumatized crista galli in 2.4% of patients. A pneumatized anterior
      clinoid process was found in 0.5% of the patients. The data obtained in our study
      were compared with those reported in other anatomic and radiologic studies.

PMID- 10068894
TI  - Expression of c-erb B-2 oncoprotein in cancer of the larynx in relation to
      invasion of the cartilagenous framework and prognosis.
AB  - Oncogenes are important cellular genes that in general promote in the normal
      growth regulatory pathways. The human c-erb B-2 proto-oncogene (HER-2 or neu)
      encodes a 185 kDa transmembrane putative growth factor receptor of the tyrosine
      kinase family. This oncogene has been shown to be over expressed and/or amplified
      in primary carcinoma of the breast, ovary, pancreas and salivary glands. This
      study was conducted to evaluate a possible link between amplification of c-erb B
      2 oncoprotein and cartilage invasion in laryngeal carcinoma. In addition, data
      concerning overexpression were compared to other clinicopathological parameters
      as well as clinical outcomes. In all, 34 patients with squamous cell carcinoma of
      the larynx were studied prospectively. Total laryngectomy specimens were sliced
      in horizontal sections at 4- to 5-mm intervals. Specimens were preserved in 10%
      formalin, and histopathological examinations were carried out after embedding
      tissues in paraffin sections and then staining them with hematoxylin and eosin.
      Detection of c-erb B-2 oncoprotein overexpression was carried out with a
      polyclonal antibody and an avidin-biotin kit. The level of c-erb B-2
      overexpression was determined using the Quantimet 520 Leica image analyzing
      system. However, no significant correlation was found between cartilage invasion
      and clinicopathological parameters and prognosis. Overexpression of c-erb B-2
      attained no significant correlation with clinicopathological parameters. In
      contrast, the correlation of c-erb B-2 overexpression and cartilage invasion was
      statistically significant (P = 0.034). In general, overexpression of c-erb B-2
      oncoprotein was related to the more aggressive tumors with high capability of
      invading laryngeal cartilages. Patients with +ve c-erb B-2 oncogene had a poor
      prognosis but this was not statistically significant when compared to the
      clinical outcomes of patients with the -ve c-erb B-2 oncogene.

PMID- 10068895
TI  - The impact of preoperative tracheotomy on T3 transglottic carcinomas of the
      larynx.
AB  - To evaluate the impact of the practice of a preoperative tracheotomy and
      different prognostic factors reported in the literature in patients with
      transglottic carcinoma of the larynx, a retrospective study was performed in the
      Instituto Nacional de Cancerologia, Mexico City. In all, 90 cases with T3
      transglottic squamous cell carcinoma requiring a total laryngectomy as primary
      treatment were studied. Prognostic factors such as the Karnofsky index, tumor
      differentiation, surgical margins and preoperative tracheotomy were analyzed by a
      Cox's proportional hazards model. The Kaplan-Meier method and log rank test were
      used to evaluate the disease-free intervals and survival curves. Thirty-two
      patients had preoperative tracheotomies, while 58 did not. Eighty percent of the
      patients in the non-preoperative tracheotomy group were alive after 5 years
      versus 20% of those with preoperative tracheotomies (P < 0.001). Although
      possibly controversial, our findings indicate that a pretreatment tracheotomy
      should be avoided in T3 transglottic obstructive lesions. In patients with these
      lesions and a subglottic extension < or = 3 cm we recommend an emergency total
      laryngectomy when possible to increase survival and decrease surgical morbidity.

PMID- 10068896
TI  - Four cases of familial hearing loss with large vestibular aqueducts.

PMID- 10068897
TI  - Poly(ADP-ribose) synthesis in cells undergoing apoptosis: an attempt to face
      death before PARP degradation.

PMID- 10068898
TI  - Subcellular localization of estradiol receptor in MCF7 cells studied with
      nanogold-labelled antibody fragments.
AB  - Ultrastructural localization studies of estradiol receptor in hormone-deprived
      and hormone-stimulated MCF7 cells were done using F(ab') fragments of three
      different antibodies (#402, 13H2, HT277) covalently linked to nanogold. These
      ultra-small, non-charged immunoreagents, combined with a size-enlargement by
      silver enhancement, localized estradiol receptor in both nuclear and cytoplasmic
      areas of non-stimulated target cells; stimulation with the steroid induced a
      predominantly nuclear labelling. In the cytoplasm of resting cells, tagging was
      often observed at or in the proximity of stress fibers. In the nucleus a large
      proportion of receptor was found inside the nucleolus, specially with the reagent
      derived from antibody 13H2. We postulate that different accessibilities of
      receptor epitopes account for the different labelling densities observed at
      cytoskeletal elements and the nucleoli.

PMID- 10068899
TI  - Histochemical staining of chromium with 2-(8-quinolylazo)-4,5-di-p
      tolylimidazole.
AB  - A new highly sensitive staining agent for chromium (Cr) has been introduced. This
      staining agent, 2-(8-quinolylazo)-4,5-di-p-tolylimidazole (QTI), was found to be
      more than ten times as sensitive for Cr than the conventional staining agent,
      Chromazurol S, and QTI also stained cadmium, copper, lead and zinc.
      Differentiation between the staining of Cr and other metals was achieved by
      immersing the tissue sections in dilute alkylamine solutions before they were
      stained with QTI. Thus, it was possible to selectively stain for Cr by blocking
      other metals.

PMID- 10068900
TI  - LFA-1 mediated cell adhesion induces G0-G1 transition of human T lymphocytes in
      vitro.
AB  - Proliferation of mature T lymphocytes requires antigenic stimulation of the T
      cell receptor/CD3 complex (TCR/CD3) and an additional signal provided by
      different accessory molecules, including the leukocyte adhesion receptor LFA-1.
      We have used a cytochemical approach to analyse the effect of LFA-1 stimulation,
      either alone or in association with TCR/CD3 triggering. A dual parameter
      cytometric analysis of DNA content versus Ki-67 positivity allowed progression
      throughout the cell cycle to be monitored. Engagement of LFA-1 alone was able to
      initiate the intracellular events necessary for Ki-67 expression (marking G0-G1
      transition) in a fraction of the T cell population but was not sufficient to
      induce the transit into S-phase. Cross-linking of both LFA-1 and CD3 was required
      for DNA synthesis to occur. These data confirm LFA-1 as an important
      costimulatory molecule of TCR-mediated T cell activation.

PMID- 10068901
TI  - Cell loss and proliferation in non-small cell lung carcinoma: correlation with
      histological subtype.
AB  - BACKGROUND: Cell kinetic data are important indicators of the aggressiveness of
      tumor and treatment response. The size of a neoplasm depends on the balance
      between cell proliferation and death. Thus, the analysis of the kinetics of cell
      proliferation and death may explain differences in the rates of tumour
      progression. METHODS: We studied apoptosis and proliferative indices in 95 cases
      of non-small cell lung carcinomas. The analysis was performed on paraffin
      embedded tissue, by both MIB-1 immunocytochemical detection to establish the
      proliferation index and the in-situ end labelling method for the apoptosis index.
      The two indices were related. RESULTS: Our results showed a high proliferative
      index and cell loss rate in squamous cell carcinoma, and a low proliferative
      index and cell loss rate in adenocarcinoma, suggesting two different growth
      patterns. CONCLUSION: These findings could explain the different biological
      behaviour and treatment response of the tumours. The tendency of a cancer cell to
      undergo apoptosis may be especially important for the chemotherapy of malignant
      tumours with a low growth rate, which are typically resistant to cytostatic
      agents.

PMID- 10068902
TI  - Comparative study of microbiological and histopathological techniques used for
      the detection of Helicobacter pylori.
AB  - This study evaluates the sensitivity, specificity and predictive values of
      several techniques commonly used for the detection of Helicobacter pylori in an
      analysis of 105 biopsy specimens (gastric and duodenal). For comparative
      purposes, the techniques investigated were divided into 2 groups:
      histopathological and microbiological. The former included hematoxylin-eosin and
      Giemsa stains, a Gram stain modified for use in tissue, and immunohistochemical
      techniques. Microbiological analysis was performed using culture, the urease test
      and the conventional Gram stain. The immunohistochemical techniques proved to be
      the most sensitive (93%). The modified Gram stain was sufficiently sensitive
      (92%) and specific (97%) for the detection of the bacterium. When combined with a
      microbiological technique such as the urease test, this stain showed increased
      sensitivity (96%) but its specificity was reduced to 94%. This combination of
      tests is recommended for the detection of H. pylori in biopsy specimens since it
      is easily performed at low cost and gives excellent results. For economical
      reasons, it is suggested that the use of immunohistochemical techniques should be
      restricted to specific cases.

PMID- 10068903
TI  - Immunohistochemical localization of bioactive substances in the epidermis of the
      earthworm, Lumbricus terrestris (Annelida, oligochaeta).
AB  - Serotonin (5HT), endothelin-big (ET-big) and neuron-specific enolase (NSE) are
      present in some epithelial paraneuronal cells of vertebrates. In the
      invertebrates, we show for the first time, by immunofluorescence and
      immunoperoxidase methods, the immunoreactions to antibodies raised to ET, 5-HT
      and NSE in the epidermis of the Lumbricus terrestris. It is assumed that the
      reactive cells are small granular cells that may have a paracrine action in the
      mechanisms of cell proliferation and secretory processes. The function of these
      bioactive substances in the epidermis of the earthworm awaits investigation.
      Phylogenetically it is very interesting that paraneuronal-like type of cells
      appear in such an ancient species of invertebrate which uses the epidermis for
      various functional activities.

PMID- 10068904
TI  - Muscarinic drugs affect cholinesterase activity and development of eye structures
      during early chick development.
AB  - During neurogenesis, markers of the cholinergic system are present in the eye and
      visual cortex of vertebrates. In adult vertebrates, a role for these molecules,
      including muscarinic acetylcholine receptors (mAChRs), in eye growth non
      accommodative regulation is also known. In order to understand the biological
      mechanisms triggered by the cholinergic system in these events, we analysed the
      effects of a cholinergic agonist (10(-4) M carbachol) and an antagonist (10(-4) M
      atropine) of the muscarinic receptors, on early chick development. To establish
      if the cholinergic system also plays a role in the regulation of early
      neurogenetic signals, the drug treatments were made at stage 5-6 HH, during the
      formation of the cephalic process. Specific effects on forehead, and in
      particular on eye development were found; carbachol treated embryos presented
      huge and well pigmented eyes, significantly different from controls. The eyes of
      atropine-exposed embryos presented anomalies with different phenotypes ranging
      from strongly affected features to normal-like appearance. Generally, the eyes
      were smaller as compared to the controls, with a number of anomalies, also in the
      normal-like phenotype, including retina and lens defects. In these structures,
      distribution of cholinesterase activities was checked by histochemical methods,
      and the amount of cells undergoing nuclear disgregation was revealed by DAPI
      staining. We propose that the drugs affected the known nervous and pre-nervous
      functions of the cholinergic markers, such as cell signalling during primary
      induction, and regulation of cell death by ACh receptors.

PMID- 10068905
TI  - Role of computer-assisted analysis of the corneal endothelium in vitreoretinal
      surgery with intraocular silicone oil injection: a technical report.
AB  - The innermost lining of the cornea consists of a single layer of cells called the
      endothelium. Despite its name, the endothelium of the cornea differs considerably
      from the vascular endothelium, both functionally and morphologically. The corneal
      endothelium plays a fundamental role in maintaining the transparency of the
      corneal membrane, as the result of both its function as a barrier against
      penetration of the aqueous humor in the parenchyma and its ability to remove
      water from the stroma (usually referred to as the endothelial "pump" function).
      Any abnormality in the corneal endothelium causes, first, the impairment of its
      function as a barrier and pump due to the loss of stromal anti-turgor mechanisms,
      followed by edema and possible development into keratopathy. The specular
      microscope is an instrument which makes it possible to see the endothelial
      "mosaic" in the reflected image of the posterior corneal surface. A large variety
      of clinical specular microscopes is presently available, both contact and non
      contact, which allow, for easy and rapid photography of the corneal endothelium
      "in vivo". In the present case, we used a non-contact computerized specular
      microscope to analyze the corneal endothelium in a group of patients affected by
      retinal detachment who needed to undergo vitreoretinal surgery with immission of
      silicone oil into the vitreal chamber.

PMID- 10068906
TI  - Heterogeneity and susceptibility to apoptosis of human renal carcinoma cells in
      vitro.
AB  - Tumors are heterogeneous in terms of morphology and susceptibility to drugs or
      radiation. Among primary and metastatic cells of a human renal carcinoma, a
      population (type II) of larger cells with prominent nucleoli, eosinophilic
      globules of intermediate filaments in paranuclear bundles, margination of
      subcellular organelles and peripheral pools of glycogen was evident. Paranuclear
      structures were recognized by monoclonal antibodies specific for cytokeratin 8,
      18 and 19, but not by vimentin specific antibodies. We propagated a cell line in
      vitro (referred to as BKR cells), and observed culture in vitro, the almost
      complete disappearance of the type II cells. Pharmacological agents that
      influence cell differentiation, such as retinoic acid, rescued the expression of
      type II cells in vitro. Long-term treatments with insulin or alpha-interferon,
      but not with the epithelial growth factor (EGF), similarly differentiated BKR
      cells and abated their susceptibility to spontaneous and actinomycin-D induced
      apoptosis. These data support the contention that differentiation of tumor cells
      is actively maintained in vivo and further strengthen the caveat on tumor lines
      stabilized in vitro, that poorly represent the morphologic and antigenic
      heterogeneity of neoplasms in vivo.

PMID- 10068907
TI  - In vitro production of IFN-gamma correlates with CA repeat polymorphism in the
      human IFN-gamma gene.
AB  - The DNA sequence of the human IFN-gamma gene shows the presence of a variable
      length CA repeat in the first intron of the gene. We investigated the allele
      distribution of this microsatellite region in 164 unrelated healthy individuals,
      and the association with interferon-gamma (IFN-gamma) production. In vitro
      production of IFN-gamma showed a significant correlation with the presence of
      allele #2.

PMID- 10068908
TI  - Cis-trans complementation of DQA1-DQB1 genes are modulated by DQ alleles: an
      immunogenetics analysis of DQ association with the down-regulatory function of
      CD8 cells in trichosanthin-induced immunosuppression.
AB  - The initiation of a CD8 cell-mediated pathway (M+) was adopted as a phenotypic
      trait to analyse genetic predisposition in trichosanthin (Tk)-induced immuno
      suppression. Tk is a natural protein antigen with 247 amino acid residues. Based
      on DNA typing for DR, DQ, DP and TAP genes, data in this paper indicate that only
      DQ genes were primarily involved and that the alleles DQA1*0501 and DQB1*0201
      were strongly associated with the M+ phenotype in cis (on DR3 haplotype) or trans
      (on DR5/DR7 heterozygotes) complementation. This is consistent with our
      observation that only the DQ-positive cells were capable of expanding after being
      co-cultured with Tk for 96 h. Two points of interest were noted. (1) The
      susceptible haplotype DRB1*0301-DQA1*0501-DQB1*0201 showed an association with
      the M+ phenotype only if combined with DRB1*04-, DRB1*08-, or DRB1*09-related
      haplotypes. When co-presented with DRB1*11-, DRB1*15-, DRB1*07-related
      haplotypes, however, no cis complementation could be detected. A detailed
      analysis of the association patterns indicated that the DQB1 locus of the non
      susceptible haplotypes was the main factor for up- or down-modulation. (2) For M+
      phenotype-related trans complementation in Tk-induced suppression, it was found
      that not only DQA1*0501-DQB1*0201 (DR5/7) alleles, but also associated DQA1*0301
      DQB1*0201 (DR4/7, 9/7) alleles, were involved. The allele DQB1*0201 was not
      associated with the DQA1 alleles in DRB1*01-, DRB1*15-, DRB1*13-, DRB1*07-related
      haplotypes. The results obtained indicate that there are some additional genetic
      factors involved in the functional expression of cis and trans complementation of
      DQA1 and DQB1 genes, among which the DQ alleles play a critical role as self
      regulators.

PMID- 10068909
TI  - HLA-DQA1 alleles and the presence of Helicobacter pylori antibodies.
AB  - Recent reports suggest that the HLA-DQA1 gene may be important in determining
      susceptibility to and outcome of Helicobacter pylori infection. To determine if
      there is an association between HLA-DQA1 alleles and H. pylori antibodies, DQA1
      alleles and H. pylori-specific antibodies were determined in 199 random subjects
      of Finnish origin (mean age 43 years, range 22-69 years). H. pylori-specific
      class IgG antibodies were measured using the EIA method (Pyloriset-EIA-G, Orion
      Diagnostica, Espoo, Finland). HLA-DQA1 typing was carried out using PCR-SSP (PCR
      with sequence-specific primers). There were 64 subjects with H. pylori-specific
      class IgG antibodies (ab+) and 135 subjects without H. pylori-specific class IgG
      antibodies (ab-). Gene and phenotype frequencies of HLA-DQA1 alleles were similar
      in the ab+ and ab- subjects (P = NS). The data suggest that no single HLA-DQA1
      allele is associated with the presence of serum antibodies against H. pylori.

PMID- 10068910
TI  - HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting
      articular and extraarticular disease manifestations.
AB  - In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on
      disease progression and genetic predisposition among 201 RA patients. We clearly
      confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA
      amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta
      chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA
      patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28%
      vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients
      was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3
      (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and
      personal disability determined using the Health Assessment Questionnaire (HAQ)
      was significantly increased among patients positive for the HVR3 motif with the
      worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no
      association of the shared HVR3 AA cassette and disease severity in the majority
      of patients presenting systemic (extraarticular) disease. Homozygosity for the
      shared HVR3 motif was only marginally increased among patients presenting
      'severe' extraarticular disease in comparison to patients with articular disease
      (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more
      often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR
      independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients
      and controls. Our analysis supports the predominant role of HLA-DR for genetic
      susceptibility to RA. In the clinical setting, however, HLA-DR typing may be
      limited to assess the individual risk of patients for disease progression.

PMID- 10068911
TI  - Molecular cloning and sequencing of feline CD56 (N-CAM).

PMID- 10068912
TI  - Molecular matching in allogeneic bone marrow transplantation.

PMID- 10068913
TI  - General hospital psychiatry in the 21st century: will old acquaintance be forgot?

PMID- 10068914
TI  - Hypochondriasis vs. anxiety disorders: why should we care?

PMID- 10068915
TI  - The relationship of hypochondriasis to anxiety disorders.
AB  - There is evidence from the literature of phenomenological overlap between
      hypochondriasis and several anxiety disorders, including specific phobia, panic
      disorder with agoraphobia, generalized anxiety disorder, and obsessive-compulsive
      disorder. Even though the boundaries of these disorders are specifically
      addressed in the DSM-IV criteria, there is evidence of anxiety and phobic
      symptoms among hypochondriacal patients and hypochondriacal concerns among
      patients with these various anxiety disorders. Beyond that there appears to be
      considerable shared comorbidity. However, the data remain limited and few direct
      comparisons have been made between hypochondriacal and anxious patients belonging
      to particular diagnostic categories. Subtypes of hypochondriasis may exist. In
      fact, the clearest link would seem to be between the illness phobia subtype and
      other phobic disorders, although this subgroup has had little study. Thus,
      hypochondriasis is distinct from the anxiety disorders but, because of
      phenomenological similarities and extensive comorbidity, consideration should be
      given to classifying it among them.

PMID- 10068916
TI  - Do viruses cause depressive illness?

PMID- 10068917
TI  - Infectious mononucleosis: psychological symptoms during acute and subacute phases
      of illness.
AB  - Although anecdotal reports suggest that anxiety and depressive disorders may be
      precipitated by acute infectious mononucleosis (AIM), there are few population
      based studies measuring distress and psychiatric disorder during and after
      infection. The purpose of this research was to study the prevalence of
      psychiatric disorders and psychological distress in patients with AIM at initial
      infection and over the subsequent 6 months. In addition, we examined the
      correlation of baseline biopsychosocial factors with distress at 2 and 6 months
      postillness. A population-based cohort with AIM was surveyed at initial infection
      and at 2- and 6-month follow-up visits. Measures included physical and laboratory
      examinations, trait and state measures of psychological and somatic distress,
      locus of control, social support, and functioning. Patients also received a
      structured psychiatric interview during the initial infection. Although transient
      psychological distress was common during acute infection, few patients met
      criteria for DSM-III-R psychiatric illness. Greater distress at 2 months was
      associated with significantly lower social functioning in the month prior to
      diagnosis and higher aspartate aminotransferase (SGOT/AST) levels, less
      confidence in the physician and health care system (locus of control), and less
      severe physical symptoms of AIM at baseline. Greater distress at 6 months was
      associated with an increased number of adverse life events in the 6 months after
      developing AIM and more days of reduced activity in the 2 weeks prior to the
      onset of AIM. This population-based study suggests that few subjects develop DSM
      III-R psychiatric disorders with AIM. Both biological and psychosocial factors
      are highly correlated with psychosocial distress at 2 months, whereas
      psychosocial factors are more important at 6-month follow-up.

PMID- 10068918
TI  - Frequent attenders without organic disease in a gastroenterology clinic. Patient
      characteristics and health care use.
AB  - We used a hospital computer to identify 50 patients (35 women, 15 men) satisfying
      research criteria for "frequent attenders" at a gastroenterology outpatient
      clinic (four or more visits to a general hospital clinic in the previous 12
      months). Their mean duration of symptoms was 5 years, and 80% reported fatigue as
      a significant complaint. Thirteen (37%) of the women were also consulting a
      gynecologist, and in nine of these their status was normal. Seven (21%) of the 35
      women who were interviewed had a history of childhood sexual abuse, and these
      patients reported significantly more lifetime somatic symptoms (9.7, SD = 3.8)
      than those without such a history (5.4, SD = 3.5, p = < 0.01). The 50 patients
      reported high levels of disability and psychological distress, and were more
      likely to rate the probability of their symptoms as being due to "bowel disease"
      than to "stress" or "other problems." Forty-five patients had at least one
      current psychiatric diagnosis and 24 at least two, with somatoform disorders
      being the most common. Nineteen (38%) reported infrequent panic attacks, but only
      three had somatization disorder. The mean number of lifetime somatic symptoms was
      5.9 (SD = 3.6; range 1-14). Seventeen patients (35%) also satisfied criteria for
      frequent attending in primary care (> 12 visits over the previous 12 months), and
      the patients reported a mean number of 5.7 (SD = 2.1) specialist appointments in
      the previous year. There may be a case for using the hospital computer to
      identify frequent attenders proactively at an earlier stage of their hospital
      visits so that appropriate management can be instituted. If such patients can be
      identified in this way, their assessment and management might be more
      appropriately supervised in designated clinics by more experienced
      gastroenterology staff.

PMID- 10068919
TI  - "INTERMED": a method to assess health service needs. I. Development and
      reliability.
AB  - The purpose of this paper is to describe the development and to test the
      reliability of a new method called INTERMED, for health service needs assessment.
      The INTERMED integrates the biopsychosocial aspects of disease and the
      relationship between patient and health care system in a comprehensive scheme and
      reflects an operationalized conceptual approach to case mix or case complexity.
      The method is developed to enhance interdisciplinary communication between (para
      ) medical specialists and to provide a method to describe case complexity for
      clinical, scientific, and educational purposes. First, a feasibility study (N =
      21 patients) was conducted which included double scoring and discussion of the
      results. This led to a version of the instrument on which two interrater
      reliability studies were performed. In study 1, the INTERMED was double scored
      for 14 patients admitted to an internal ward by a psychiatrist and an internist
      on the basis of a joint interview conducted by both. In study 2, on the basis of
      medical charts, two clinicians separately double scored the INTERMED in 16
      patients referred to the outpatient psychiatric consultation service. Averaged
      over both studies, in 94.2% of all ratings there was no important difference
      between the raters (more than 1 point difference). As a research interview, it
      takes about 20 minutes; as part of the whole process of history taking it takes
      about 15 minutes. In both studies, improvements were suggested by the results.
      Analyses of study 1 revealed that on most items there was considerable agreement;
      some items were improved. Also, the reference point for the prognoses was changed
      so that it reflected both short- and long-term prognoses. Analyses of study 2
      showed that in this setting, less agreement between the raters was obtained due
      to the fact that the raters were less experienced and the scoring procedure was
      more susceptible to differences. Some improvements--mainly of the anchor points-
      were specified which may further enhance interrater reliability. The INTERMED
      proves to be a reliable method for classifying patients' care needs, especially
      when used by experienced raters scoring by patient interview. It can be a useful
      tool in assessing patients' care needs, as well as the level of needed adjustment
      between general and mental health service delivery. The INTERMED is easily
      applicable in the clinical setting at low time-costs.

PMID- 10068920
TI  - "INTERMED": a method to assess health service needs. II. Results on its validity
      and clinical use.
AB  - The validity and clinical use of a recently developed instrument to assess health
      care needs of patients with a physical illness, called INTERMED, is investigated.
      The INTERMED combines data reflecting patients' biological, psychological, and
      social characteristics with information on health care utilization
      characteristics. An example of a patient population in which such an integral
      assessment can contribute to the appropriateness of care, are patients with low
      back pain of degenerative or unknown origin. It supports the validity and the
      clinical usefulness of the INTERMED when clinically relevant subgroups in this
      heterogeneous population can be identified and described based on their INTERMED
      scores. The INTERMED was utilized in a group of patients (N = 108) having low
      back pain who vary on the chronicity of complaints, functional status, and
      associated disability. All patients underwent a medical examination and responded
      to a battery of validated questionnaires assessing biological, psychological, and
      social aspects of their life. In addition, the patients were assessed by the
      INTERMED. It was studied whether it proved to be possible to form clinically
      meaningful groups of patients based on their INTERMED scores; for this, a
      hierarchical cluster analysis was performed. In order to clinically describe
      them, the groups of patients were compared with the data from the questionnaires.
      The cluster analysis on the INTERMED scores revealed three distinguishable groups
      of patients. Comparison with the questionnaires assessing biological,
      psychological, and social aspects of disease showed that one group can be
      characterized as complex patients with chronic complaints and reduced capacity to
      work who apply for a disability compensation. The other groups differed
      explicitly with regard to chronicity, but also on other variables. By means of
      the INTERMED, clinically relevant groups of patients can be identified, which
      supports its use in clinical practice and its use as a method to describe case
      mix for scientific or health care policy purposes. In addition, the INTERMED is
      easy to implement in daily clinical practice and can be of help to ease the
      operationalization of the biopychosocial model of disease. More information on
      its validity in different patient populations is necessary.

PMID- 10068921
TI  - A preliminary study of staff perception of psychiatric services in general
      hospitals.
AB  - There has been increasing recognition of the importance of integrating physical
      and psychiatric care under growing economic pressure. We conducted a survey of
      staff perception on psychiatric services in four general hospitals. The purpose
      of this study was to see differences among the staff in their recognition and
      expectation of the role of the psychiatric department and the need for
      psychiatric and other staff to work more closely together. Although 81% of
      psychiatrists recognized their role in acute psychiatry, only 42.6% thought that
      acute psychiatry was the most important role of psychiatry. Mood disorders were
      recognized as a psychiatric category in 95.2% of psychiatrists and 54.8% of
      nonpsychiatrist physicians. Overall satisfaction with psychiatric services in
      psychiatric and other staff were 54.0% and 68.2%, respectively. Although 85.7% of
      psychiatrists answered that they supported staff in other departments that have
      psychiatric or psychological problems, only 53.5% of those staff in other
      departments were satisfied with their support. Staff in other departments
      expected psychiatric staff to establish consultation hotlines and to visit other
      departments regularly. Our results suggest that there are discrepancies between
      psychiatric and other staff in their perception of psychiatric services, and it
      is our belief that those gaps must be bridged for better collaboration in general
      hospitals.

PMID- 10068922
TI  - Attempted suicide. Do we understand the patients' reasons?
AB  - This explorative study compared the patients', doctors', and nurses' views
      regarding their attribution of reasons for attempting suicide and the patients'
      emotional state immediately preceding their suicide attempts. A sample of 30 out
      of 94 consecutive patients seen in the emergency room of University Hospital were
      examined shortly after they had attempted suicide. Immediately after the routine
      clinical interview, conducted by a psychiatric resident and a nurse, patients
      filled in a questionnaire giving 14 possible reasons for attempting suicide as
      well as 8 feelings characterizing the emotional state preceding the suicide
      attempt. In the meantime, and without prior discussion of the case, the resident
      and the nurse independently completed the same questionnaire. In addition,
      sociodemographic and clinical data were obtained. Intrapersonal reasons such as
      to get relief from a terrible state of mind or from an unbearable situation were
      most frequently chosen by patients, nurses, and doctors alike. The most striking
      difference was found for "loss of control": this item was chosen significantly
      more often by patients than by nurses and doctors. Accordingly, patients reported
      significantly more often feelings of anxiety/panic and emptiness (mental vacuum),
      whereas feelings of despair and powerlessness/hopelessness were mentioned most
      frequently by nurses and doctors. Mental health professionals should bear in mind
      that many suicide attempters experience feelings of anxiety/panic prior to their
      suicidal act, and that a majority report having lost control over themselves,
      thus indicating a state of emotional crisis.

PMID- 10068923
TI  - The use of clock tests in schizophrenia.
AB  - Though clock drawing tests are well recognized as measures of cognitive function,
      there is little data on the performance of patients with schizophrenia. We
      compared 24 patients with schizophrenia to 24 healthy, age-matched controls on
      clock drawing, copying, and reading. Patients with schizophrenia performed
      significantly worse on clock drawing and copying despite the fact that the groups
      had similar scores on the MMSE. Worse performance was associated with higher
      scores on the BPRS. Clock drawing and copying may be useful for the assessment of
      cognition in schizophrenia, and the monitoring of cognitive changes associated
      with antipsychotic medication.

PMID- 10068924
TI  - [Dermatologic rehabilitation--chances in crisis].
AB  - The political activities concerning the health care system in recent months have
      made the chronic crisis involving dermatological rehabilitation clinics in
      Germany more apparent. While dermatology has continual to evolve in acute care
      clinical facilities, no critical analysis of dermatological rehabilitation
      clinics has occurred. A commonly accepted, standardized document defining
      precisely the goals of dermatological rehabilitation as well as the appropriate
      ways to measure the quality of the treatment and its results is not available. An
      expert panel appointed by the responsible working group of the Bavarian public
      health care system succeeded in defining mandatory structural requirements which
      will soon be obligatory for all Bavarian dermatological rehabilitation clinics.
      In the future, a general concept for the medical care of patients with chronic
      dermatological diseases on the appropriate level--ambulatory or hospital--has to
      be established. A close cooperation between clinicians working in acute care
      facilities and dermatologists in ambulatory practices could, at least in the long
      run, result in establishing local and national centers of competence for
      diagnosis, therapy, prevention, and rehabilitation of chronic dermatological
      diseases.

PMID- 10068925
TI  - [Melatonin in dermatology. Experimental and clinical aspects].
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in
      humans, produced by the pineal gland and stimulated by beta-adrenergic receptors.
      Serum melatonin levels exhibit a circadian rhythm with low levels during the day,
      rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin
      participates in the regulation of several physiological processes such as
      seasonal biological rhythm, daily sleep induction, aging and modulation of
      immunobiological defence reactions. Furthermore, melatonin has a highly
      lipophilic molecular structure facilitating penetration of cell membranes and
      serving as an extra- and intracellular free radical scavenger. Melatonin seems to
      quench mainly hydroxyl radicals, the most damaging of all free radicals.
      Melatonin may play a role in the etiology and treatment of several dermatoses
      e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin
      on hair growth is another aspect. Topical application of melatonin inhibits the
      development of UV-erythema. Penetration through skin after topical application
      and oral bioavailability auxit further investigations on the pharmacokinetic and
      pharmacodynamic actions of melatonin.

PMID- 10068926
TI  - [Interleukin-10 in dermatology].
AB  - In recent years the investigation of cytokines has been a focus of scientific
      interest in order to understand the pathogenesis of a variety of diseases. In
      additions cytokines are increasingly being used for therapeutic purposes,
      including dermatologic disorders. IL-10 is a recently described cytokine with
      anti-inflammatory and immunosuppressive qualities which plays an important role
      in immunoregulation. The overexpression of this mediator has been proven in some
      inflammatory dermatoses as well as in various skin tumors. These observations
      help to understand down regulatory events in hyper-inflammatory conditions such
      as allergic or toxic dermatitis on the one hand and the suppression of an
      adequate anti-tumor response and thereby the progression of malignant tumors on
      the other hand. Recent investigations indicate a relative IL-10 deficiency in
      psoriasis. Initial therapeutic applications of IL-10 in psoriasis underline the
      pathophysiological importance of this cytokine.

PMID- 10068927
TI  - [Model of a special consultation for patients with atopic eczema].
AB  - Due to its high prevalence, atopic dermatitis is an important problem in the
      dermatologic practice. The chronicity of the disease together with numerous
      triggering factors of varying individual impact create a complex situation which
      is difficult to manage under the current circumstances in our health care system.
      We describe the concept of an outpatient clinic especially for atopic dermatitis
      as established in our Department of Dermatology. A high degree of standardization
      is combined with a high measure of individual care. The aims of this clinic are
      an optimized outpatient management of atopic dermatitis, the gathering of
      epidemiologic data, the performance of controlled studies, and potentially the
      reduction of costs.

PMID- 10068928
TI  - [Phototherapy in severe atopic dermatitis. Comparison between current UVA1
      therapy, UVA1 cold light and combined UVA-UVB therapy].
AB  - Severe atopic dermatitis, especially when involving the face, does not respond
      well to conventional therapy. In the present prospective randomized trial, we
      compared therapeutic efficiency of medium-dose UVA1, medium-dose cold light UVA1
      (15 treatment courses with 50 J/cm2 each) and combined UVA-UVB phototherapy. Four
      (13.3%) of 30 UVA1 treated patients, one (3.4%) of 30 UVA1 cold light treated
      patients and three (30%) of 10 patients treated with combined UVA-UVB
      discontinued therapy course before finishing treatment protocol because skin
      status did not improve or even deteriorated. In the other patients treated over a
      period of three weeks, skin status improved significantly or even cleared
      completely in 80.8% of UVA1 treated and in 89.7% of UVA1 cold light treated
      patients resulting in a significant decrease of the SCORAD-Score (UVA1 group from
      68.6 +/- SD 10.9 to 29.8 +/- SD 7.1 and UVA1 cold light group from 72.5 +/- SD
      13.4 to 23.8 +/- SD 11.6; p < 0.05 each). In the UVA-UVB treated group, the
      SCORAD-Score also decreased (from 71.0 +/- SD 9.4 to 41.6 +/- 10.5), but
      significantly less than in both UVA1 treated groups (p < 0.05 each). Four weeks
      after completing therapy UVA1 treated patients showed a prolonged therapy benefit
      as compared to UVA-UVB treated patients. Plasma levels of eosinophil cationic
      protein and soluble interleukin-2 receptor significantly decreased under UVA1
      phototherapy but not under UVA-UVB therapy. Compared to conventional UVA1
      phototherapy, UVA1 cold light phototherapy showed advantages due to the absence
      of potentially proinflammatory effects based on temperature-induced increase of
      skin blood flow (quantified by Laser doppler scanning) and increased sweat
      production (determined by the patient using a visual analog scale).

PMID- 10068929
TI  - [Cyclical intravenous antibiosis as an effective therapy concept in chronic
      recurrent erysipelas].
AB  - The treatment of choice for prevention of recurrent erysipelas is the long-term
      therapy with intramuscular penicillin. The results are often unsatisfactory.
      Usually erysipelas recurs when the treatment is stopped. The aim of the present
      study was to evaluate a new treatment regimen, consisting of intravenous
      penicillin combined with lymphatic drainage. Fifteen patients who had suffered
      from three or more episodes of erysipelas within the last two years received 10
      Mega I.U. of penicillin per day over ten days every third month over a one year
      period (patients who were allergic to penicillin received erythromycin). Use of
      intravenous penicillin was combined with lymphatic drainage performed by a
      sequential pneumatic compressing device. The treatment results were assessed by
      clinical examination and laboratory tests as well as by laser Doppler imaging
      every third month. During the one year treatment period and a further year of
      follow-up, 14 of 15 patients had no recurrent erysipelas. Only a 65 year old
      patient suffering from Parkinson heart failure, chronic lymphedema and an
      extensive stasis ulcers had recurrent erysipelas. The present treatment regimen
      appears to be an effective therapy for prevention of recurrent erysipelas.

PMID- 10068930
TI  - [Unilateral latero-thoracic exanthema in childhood. Clinical characteristics and
      diagnostic criteria in 5 patients].
AB  - Unilateral laterothoracic exanthem a (ULE) is a self-limited, probably infectious
      allergic skin disease predominantly affecting small children. We describe five
      such cases. The typical unilaterally located or at least unilaterally dominant
      exanthem usually starts in the axillary region and is characterized by red,
      partly confluent papules and fine scales. Two of the children presented with
      atypical manifestations of ULE. Due to its asymptomatic course, therapy is not
      necessary in the majority of cases.

PMID- 10068931
TI  - [Proliferating trichilemmal cyst with focal segments of metastatic squamous
      epithelial carcinoma].
AB  - A large ulcerated tumor covered the right hemisphere of the scalp of a 77 year
      old woman. By histological, immunohistological, and electronmicroscopical
      examination, a proliferating trichilemmal cyst with focal areas of a poorly
      differentiated squamous cell carcinoma was identified. Six months after
      extirpation of the entire tumor and dissection of supraomohyoidal lymph nodes,
      metastases in nuchal and supraclavicular lymph nodes and soft tissue of the neck
      became apparent. The present case underlines the necessity of a preoperative
      diagnostic evaluation and of radical surgical treatment for proliferating
      trichilemmal cysts.

PMID- 10068932
TI  - [Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine
      intolerance. A follow-up over 20 years].
AB  - A 58 year old patient with hepatitis virus C (HCV) infection had a secondary
      polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the
      patient suffered from progressive pigmented purpura (PPP). Histologic evaluation
      revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of
      the PPP, as demonstrated with controlled oral provocation testing. In most of the
      previously described cases of HCV and type III cryoglobulinemia, the typical
      cutaneous finding was palpable purpura with leukocytoclastic vasculitis.

PMID- 10068933
TI  - [An unusual hemorrhagic variant of Stevens-Johnson syndrome in an HIV-infected
      patient].
AB  - Cutaneous adverse drug reactions in HIV-positive patients with their wide
      spectrum of manifestations remain a diagnostic and therapeutic challenge. Skin
      diseases as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal
      necrolysis belong to this group. The typical primary lesions are erythematous
      macules and papules, which rapidly extend to the entire body and may be
      accompanied by a extensive epidermal detachment. Diagnosis and immediate therapy
      is indispensable because of the possible fulminant course of the disease. We
      report a HIV-positive patient with a cutaneous adverse drug reaction showing
      predominantly hemorrhagic lesions.

PMID- 10068934
TI  - [Synergistic effects of terbinafine and itraconazole antimycotics].

PMID- 10068935
TI  - [A prospective comparison of octylcyanoacrylate tissue adhesive and conventional
      wound closure].

PMID- 10068936
TI  - [The Tubingen "Video-Live" Congresses: examples for modern interactive and
      multimedia education].

PMID- 10068937
TI  - [Sonography of lymph nodes and subcutis in dermatology. 2].

PMID- 10068938
TI  - Immunomodulators in human seminal plasma: a vital protection for spermatozoa in
      the presence of infection?

PMID- 10068939
TI  - Prospects and problems for germ cell transplantation in the male.

PMID- 10068940
TI  - Y bind RNA for spermatogenesis?

PMID- 10068941
TI  - Secular and seasonal changes in semen quality among young Danish men: a
      statistical analysis of semen samples from 1927 donor candidates during 1977
      1995.
AB  - The objective of this study was to investigate whether semen quality has changed
      during the years 1977-1995 in a group of unselected semen donor candidates, and
      to determine whether semen quality is subject to seasonal variation, by analysis
      of time- and season-related changes in semen quality using multiple regression
      and ANOVA. The study was based on analysis of the first semen sample delivered by
      1927 semen donor candidates in Copenhagen during the period 1977-1995, with
      determination of semen volume, sperm concentration, total sperm count, percentage
      motile spermatozoa, and a semiquantitative sperm motility score. Multiple linear
      regression analysis with year, sexual abstinence and season as covariates showed
      a significant increase in mean sperm concentration from 53.0 x 10(6)/mL in 1977
      to 72.7 x 10(6)/mL in 1995 (p < 0.0001) and in mean total sperm count from 166.0
      x 10(6) to 227.6 x 10(6) (p < 0.0001). Mean semen volume and percentage motile
      spermatozoa did not change. Sperm motility deteriorated, as the spermatozoa in
      74.2% of the samples were of excellent motility in 1977-1980 compared to only
      41.9% in 1993-1995 (chi 2 = 130.0, p < 0.0001). Analysis of variance showed
      significant variation between seasons regarding sperm concentration (p < 0.0001)
      and total sperm count (p < 0.0001). Highest sperm counts were found in spring,
      with a mean concentration (95% C.I.) of 77.6 x 10(6)/mL (71.9-83.7), and lowest
      in summer, with a mean of 57.5 x 10(6)/mL (50.1-65.4). No other semen parameter
      varied with season. It is concluded that sperm counts increased, whereas sperm
      motility decreased, in a group of Danish semen donor candidates, from 1977 to
      1995. Due to the retrospective design and the anonymity of the donors, we were
      unable to control for variation in donor age, and we cannot exclude the
      possibility that some donor candidates were selected by being accepted as donors
      by other semen donor services in Copenhagen. With these limitations in mind, we
      suggest our results should be interpreted cautiously and regarded as a
      contribution to the ongoing dispute on whether or not there is a continuous
      decrease in sperm quality. The seasonal variations found in sperm concentration
      and total sperm count were pronounced and were not attributable to seasonal
      differences in the length of sexual abstinence. Additionally, the same seasonal
      pattern was observed in five successive year-intervals. These findings strongly
      indicate that human testicular function is influenced by season, a phenomenon
      well known in many lower mammals.

PMID- 10068942
TI  - Reactive oxygen species influence the acrosome reaction but not acrosin activity
      in human spermatozoa.
AB  - It is now widely accepted that the higher levels of reactive oxygen species (ROS)
      produced by damaged or deficient spermatozoa are associated with a loss of
      motility and a decreased capacity for sperm-oocyte fusion. Furthermore, earlier
      studies show, under physiological conditions, that some ROS may be involved in
      capacitation and hyperactivation of human spermatozoa. We measured ROS levels,
      acrosome reaction (AR) and acrosin activity (AA) in semen samples from suspected
      subfertile men to reveal the influence of ROS on AR and AA of human spermatozoa.
      Semen samples were obtained from 60 patients. Samples with > or = 1 x 10(6)
      leukocytes/mL were excluded from the study. ROS production was determined using a
      chemiluminescence technique. AR was determined using a triple stain technique.
      The percentage of acrosome-reacted spermatozoa after low temperature induction of
      the AR (test value), and the inducibility of AR (= the difference between the
      test value and the control), were calculated. The AA was analysed by determining
      the proteolytic potential of spermatozoa on gelatin plates. The mean halo
      diameter and percentage of halo formation in each sample were measured as AA
      parameters. Scatter plots of ROS levels and AR parameters showed that the
      percentage of acrosome reacted spermatozoa and AR inducibility were better in
      samples with low rather than high ROS levels. On the other hand, there were no
      apparent similarities between ROS and the AA parameters. Therefore, the
      percentage of acrosome-reacted spermatozoa and AR inducibility were significantly
      higher in the low than in the high ROS group (p = 0.028, p = 0.0001,
      respectively). In addition, there was no significant difference in AA parameters
      between groups. These findings suggest that lower ROS in semen may have a role in
      AR but excessive ROS may exert a negative influence on AR, while ROS in semen has
      no relationship to AA.

PMID- 10068943
TI  - Freezing of testicular tissue as a minced suspension preserves sperm quality
      better than whole-biopsy freezing when glycerol is used as cryoprotectant.
AB  - Frozen-thawed testicular spermatozoa have been used successfully for ICSI,
      especially in cases of obstructive azoospermia with normal spermatogenesis. Fewer
      attempts, however, have been made to check whether these rather immature
      spermatozoa, in a different environment with several other cell types present,
      have cryobiological requirements other than those of ejaculated spermatozoa. This
      is the reason why the freezing protocols and cryoprotectants (glycerol) used for
      freezing testicular tissue are based on experience with semen freezing. This
      study aimed to assess whether cryosurvival and/or motility was influenced by
      freezing of testicular tissue either as an intact biopsy or as a shredded tissue
      suspension, when glycerol was used as cryoprotectant. Freezing of testicular
      tissue as a suspension preserved motility (type B + C) significantly better than
      freezing of whole biopsies (9.2% vs. 4.0%). Similar observations have been made
      for vitality (39.3% vs. 25.4%). Centrifugation on 50% Percoll in order to remove
      the cryoprotectant resulted in a huge loss of spermatozoa (or late spermatids)
      and should therefore be especially avoided in cases of testicular failure. On the
      basis of these observations, mincing of the testicular biopsies before freezing
      may be advocated. Testicular spermatozoa seem to be better preserved when frozen
      in suspension, at least when slowly permeating glycerol is used as a
      cryoprotectant.

PMID- 10068944
TI  - Influence of age, hormones and germ cells on glutathione S-transferase activity
      in cultured Sertoli cells.
AB  - Glutathione S-transferase (GSH-S-T) activity was measured, using 1-Cl-2,4
      dinitrobenzene as substrate, in Sertoli cell cultures obtained from rats aged 10,
      18, and 26 days. The GSH-S-T activity showed a significant increase with age of
      the Sertoli cell donor. When cultures were treated with hypotonic solution, in
      order to eliminate residual contaminating germ cells, the age dependent increase
      in enzyme activity was less pronounced. FSH, but not testosterone, increased
      enzyme activity in all cultures. Addition of freshly isolated germ cells (mainly
      pachytene spermatocytes) to hypotonic-treated Sertoli cell monolayers enhanced
      GSH-S-T activity at all ages. It is concluded that GSH-S-T activity can be
      measured in cultured Sertoli cells during the period of onset of spermatogenesis
      (10-26 days). This enzyme activity is dependent on age of the Sertoli cell donor
      and is influenced by FSH and germ cells. Since GSH-S-Ts are actively engaged in
      cell detoxificative functions through conjugation of xenobiotics with
      glutathione, the present findings suggest that this enzyme may have a relevant
      protective role during the critical period when spermatogenesis is being
      established.

PMID- 10068945
TI  - Bile tolerance, taurocholate deconjugation, and binding of cholesterol by
      Lactobacillus gasseri strains.
AB  - Bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding
      ability of 28 strains of Lactobacillus gasseri were examined. There was
      significant variation among strains in growth in media containing bile and also
      variation in the ability to bind cholesterol. Cultures grown for 12 h at 37
      degrees C bound significantly more cholesterol than did cells from a 48-h
      incubation. Variation among strains in the ability to deconjugate sodium
      taurocholate was not significantly different. Maximal deconjugation of sodium
      taurocholate was achieved with the cells during the stationary phase of growth
      (12 h). Statistical analysis showed no significant correlation between bile
      tolerance and sodium taurocholate deconjugation, bile tolerance and cholesterol
      binding ability, or sodium taurocholate deconjugation and cholesterol-binding
      ability.

PMID- 10068946
TI  - The effect of lactose derivatives on intestinal lactic acid bacteria.
AB  - Nine strains of lactic acid bacteria were studied for growth and fermentation end
      products on lactulose, lactitol, and lactobionic acid. In addition, human fecal
      and biopsy isolates were screened for new potential by probiotic strains
      utilizing lactose derivatives, and one new isolate of Lactobacillus rhamnosus was
      enriched. The utilization of lactose derivatives and the effect on the
      fermentation end products were dependent on strain. Typical mixed-acid
      fermentations were observed with Lb. rhamnosus and Lactococcus lactis. Microbiota
      enriched from fecal and biopsy samples using modified MRS medium consisted mainly
      of enterococci and streptococci. The adhesion of tested strains to Caco-2 cells
      was not dependent on carbon source. The new Lb. rhamnosus strain VTT E-97800 has
      potential for further probiotic studies.

PMID- 10068947
TI  - Binding of lipophilic nutrients to beta-lactoglobulin prepared by bioselective
      adsorption.
AB  - The binding of the lipophilic nutrients, retinal, vitamin D2, and retinyl
      palmitate by beta-lactoglobulin was measured by analysis of changes in the
      fluorescence of the tryptophanyl residue of beta-lactoglobulin or the retinyl
      moiety. The fluorescence intensity of the tryptophanyl residue was quenched by
      retinoid or vitamin D binding but was enhanced by palmitate binding. The analysis
      of competitive binding experiments with palmitate indicated that retinal and
      palmitate did not compete for the same site; however, vitamin D2, which binds
      with a stoichiometry of 2, appeared to displace palmitate at higher
      concentrations. Also, the retinoids and vitamin D2 were bound more tightly than
      was palmitate. The results are consistent with the model in which the retinoids
      and vitamin D2 bind in the calyx formed by the beta-barrel; palmitate and a
      second molecule of vitamin D2 bind in a surface pocket near the dimer contact
      region. Retinyl palmitate, which has both moieties, appeared to bind at both
      sites.

PMID- 10068948
TI  - Effect of prepartum administration of monensin in a controlled-release capsule on
      milk production and milk components in early lactation.
AB  - Dry cows and pregnant heifers from 25 farms near Guelph, Ontario, Canada were
      enrolled in a large double-blind, randomized clinical trial that was designed to
      evaluate the impact of monensin on energy metabolism, health, and production. A
      total of 503 cows was given monensin in controlled-release capsules, and 507 were
      administered placebo capsules 3 wk prior to the expected calving date. The
      effects of treatment on milk production and milk components at the first three
      Dairy Herd Improvement (DHI) tests were evaluated using repeated measures
      analysis of variance. Treatment with monensin increased milk production, but this
      effect was dependent on body condition score prior to calving. Cows that were
      classified as thin (score of < or = 3.0) did not have increased production in
      response to monensin treatment. Cows with fair body condition (score of 3.25 to
      3.75) produced significantly more milk at the second DHI test (+0.85 kg), but
      cows that were fat (score of > or = 4.0) produced significantly more milk than
      did controls for all three DHI tests (+1.25 kg) in early lactation. Monensin
      significantly increased projected 305-d milk production in cows from herds at
      increased risk of ketosis. Treatment with monensin had no significant effect on
      either milk fat percentage or milk protein percentage.

PMID- 10068949
TI  - Hepatic fatty acid composition in periparturient dairy cows with fatty liver
      induced by intake of a high energy diet in the dry period.
AB  - The present study compared the hepatic fatty acid composition of cows that were
      fed a high energy diet during the dry period to induce fatty liver after
      parturition with that of control cows. Treated cows had higher concentrations of
      plasma nonesterified fatty acids as a result of greater lipolysis after
      parturition than did control cows; consequently, the treated cows accumulated
      greater amounts of triacylglycerols in the liver. Before parturition, treated
      cows had lower percentages of oleic acid and higher percentages of linoleic acid
      than did control cows, but percentages of other fatty acids were similar for both
      groups. After parturition, percentages of each fatty acid were changed
      substantially, particularly the four major fatty acids (palmitic, stearic, oleic,
      and linoleic acids). For treated cows, the percentages of palmitic and oleic
      acids were higher at 0.5 wk after parturition than at 1 wk before parturition;
      percentages of stearic and linoleic acids decreased. Unlike treated cows, the
      percentages of both oleic and linoleic acids in the control cows did not change
      during that time. Moreover, we found that when lipolysis decreased, as indicated
      by lower plasma nonesterified fatty acid concentrations, the percentages of each
      fatty acid gradually rebounded toward the concentrations measured before
      parturition; this observation indicates that the shift in hepatic fatty acid
      composition is influenced by lipolysis. The increased lipolysis after parturition
      led to a vast increase in the hepatic triacyglycerol concentration and to a shift
      in hepatic fatty acid composition.

PMID- 10068950
TI  - Effects of milk fever, ketosis, and lameness on milk yield in dairy cows.
AB  - The effects of milk fever, ketosis, and lameness were studied using data from
      23,416 Finnish Ayrshire cows that calved in 1993 and were followed for one
      lactation (i.e., until culling or the next calving). Monthly test day milk yields
      were treated as repeated measurements within a cow in a mixed model analysis.
      Disease index variables were created to relate the timing of a disease to the
      measures of test day milk. Statistical models for each parity and disease
      included fixed effects of calving season, stage of lactation, and disease index.
      An autoregressive correlation structure was used to model the association among
      the repeated measurements. The milk yield of cows contracting milk fever was
      affected for a period of 4 to 6 wk after calving; the loss ranged from 1.1 to 2.9
      kg/d, depending on parity and the time elapsed after milk fever diagnosis.
      Despite the loss, cows with milk fever produced 1.1 to 1.7 kg more milk/d than
      did healthy cows. Milk yield started to decline 2 to 4 wk before the diagnosis of
      ketosis and continued to decline for a varying time period after it. The daily
      milk loss was greatest within the 2 wk after the diagnosis, varying from 3.0 to
      5.3 kg/d, depending on parity. Cows in parity 4 or higher were most severely
      affected by ketosis; the average total loss per cow was 353.4 kg. Lameness also
      affected milk yield; milk loss of cows diagnosed with foot and leg disorders
      varied between 1.5 and 2.8 kg/d during the first 2 wk after the diagnosis.

PMID- 10068951
TI  - Postpartum body condition score and results from the first test day milk as
      predictors of disease, fertility, yield, and culling in commercial dairy herds.
AB  - The study used field data from a regular herd health service to investigate the
      relationships between body condition scores or first test day milk data and
      disease incidence, milk yield, fertility, and culling. Path model analysis with
      adjustment for time at risk was applied to delineate the time sequence of events.
      Milk fever occurred more often in fat cows, and endometritis occurred between
      calving and 20 d of lactation more often in thin cows. Fat cows were less likely
      to conceive at first service than were cows in normal condition. Fat body
      condition postpartum, higher first test day milk yield, and a fat to protein
      ratio of > 1.5 increased body condition loss. Fat or thin condition or condition
      loss was not related to other lactation diseases, fertility parameters, milk
      yield, or culling. First test day milk yield was 1.3 kg higher after milk fever
      and was 7.1 kg lower after displaced abomasum. Higher first test day milk yield
      directly increased the risk of ovarian cyst and lameness, increased 100-d milk
      yield, and reduced the risk of culling and indirectly decreased reproductive
      performance. Cows with a fat to protein ratio of > 1.5 had higher risks for
      ketosis, displaced abomasum, ovarian cyst, lameness, and mastitis. Those cows
      produced more milk but showed poor reproductive performance. Given this type of
      herd health data, we concluded that the first test day milk yield and the fat to
      protein ratio were more reliable indicators of disease, fertility, and milk yield
      than was body condition score or loss of body condition score.

PMID- 10068952
TI  - Bacillus cereus spores in raw milk: factors affecting the contamination of milk
      during the grazing period.
AB  - Psychrotrophic Bacillus cereus is a limiting factor for the shelf-life of
      pasteurized milk, particularly during the grazing season. Potential sources of
      contamination and factors that might affect the spore content of milk were
      studied in detail for a group of eight cows during three 2-wk study periods from
      June to September over 2 yr. The spore content of milk was strongly associated
      with the degree of contamination of the teats with soil. High water content of
      soil, low evaporation of water and dirty access alloys were the most important
      factors correlating with high spore concentrations. The spore content of soil
      varied from < 50 to 380,000/g, depending on time and sampling site. The milking
      equipment did not contribute significantly to the contamination. The spore
      contents in air during milking (< 100 cfu/m3) and in feed (silage, hay, fresh
      grass, and concentrates) were too low to be of importance for contamination. The
      spore content in dung was also low. Further support that soil was the major
      contamination source was found by comparison of genetic fingerprints by random
      amplified polymorphic DNA polymerase chain reaction of isolates of B. cereus from
      soil and milk and by teat cleansing experiments, which resulted in reduced
      contamination levels in milk.

PMID- 10068953
TI  - Phenotype analysis of peripheral blood mononuclear cells in periparturient dairy
      cows.
AB  - Impaired immune function during the periparturient period contributes to the
      increased susceptibility of the cow to infectious disease around the time of
      calving. Changes in subpopulations of peripheral blood mononuclear cells during
      the immediate periparturient period can contribute to the observed
      immunosuppression in cows, but it is not known exactly when and what changes
      occur. Using a flow cytometer and monoclonal antibodies directed against
      antigenic markers on mononuclear cells, the populations of CD3, CD4, CD8, and
      gamma delta T-cell receptor positive cells were examined in eight periparturient
      Jersey cows during the 2 wk before and 2 wk after parturition. The percentage of
      cells that were positive for CD3, CD4, and gamma delta T-cell receptor markers
      exhibited a significant decline before calving and reached a nadir at calving.
      These percentages did not return to precalving levels until 2 wk after calving.
      These data are compatible with the hypothesis that declining T-cell populations
      may contribute to the immunosuppression reported for dairy cows at calving.

PMID- 10068954
TI  - Water balance and fecal moisture content in suckling calves as influenced by free
      access to dry feed.
AB  - Holstein bull calves were used to examine the effect of dry feed on water balance
      and fecal moisture content during the suckling period. In Experiment 1 (n = 20
      calves), free access to concentrate and timothy hay decreased urine volume and
      increased apparent water retention, fecal water excretion, and fecal moisture
      content by 2 wk, although daily amounts of milk replacer also affected water
      balance when DMI from dry feed was low. In Experiment 2 (n = 20 calves), free
      access to concentrate and hay from wk 1 increased reabsorption of water from
      renal tubules during wk 2, resulting in reduced urine volume and increased plasma
      volume. In Experiment 3 (n = 10 calves), supplementation of 500 g/d of milk
      replacer plus free access to concentrate and hay from wk 1 increased plasma
      antidiuretic hormone by 2 wk compared with the concentration in calves receiving
      200 g/d of milk replacer alone. Plasma antidiuretic hormone concentrations were
      highly correlated with plasma concentrations of acetate and ketone bodies but not
      with glucose and urea. In Experiment 4 (n = 16 calves), apparent water retention
      and fecal moisture content during wk 2 were increased by free access to
      concentrate from wk 1 but were not affected by rice straw as an inert bulk
      source.

PMID- 10068955
TI  - The impact of a monensin controlled-release capsule on subclinical ketosis in the
      transition dairy cow.
AB  - An experiment was designed to examine subclinical ketosis in periparturient dairy
      cows and the antiketogenic effects of monensin. Subclinical ketosis was induced
      through a 10% feed restriction and was quantitatively determined using a blood
      beta-hydroxybutyrate (BHBA) threshold of 1200 mumol/L. Monensin decreased the
      BHBA concentration by 35% and increased the glucose concentration by 15%. No
      effect of monensin on milk production was detected, but rumen fermentation was
      altered. Monensin decreased the acetate to propionate ratio, decreased the
      butyrate concentration, and increased pH. The lower concentration of BHBA in
      blood and higher concentration of blood glucose in cows treated with a monensin
      controlled-release capsule decreased subclinical ketosis in early lactation cows.

PMID- 10068956
TI  - Degradability of forage proteins by in situ and in vitro enzymatic methods.
AB  - The overall objective of these two studies was to evaluate the efficacy of using
      the proteolytic enzyme from Streptomyces griseus to estimate concentrations of
      ruminally degradable protein (RDP) in a wide array of forages. In the first
      study, alfalfa and prairie hays that previously had been evaluated in vivo for
      RDP were incubated in a replicated 3 x 3 factorial combination of enzyme
      concentrations (6.6, 0.66, and 0.066 activity units/ml of incubation medium) and
      incubation times (2, 4, and 48 h). Two treatment combinations (6.6 activity units
      for 4 h and 0.066 activity units for 48 h) yielded respective RDP estimates for
      alfalfa and prairie hay that were close to the known in vivo values. In the
      second study, 20 diverse forages were evaluated for RDP by using the in situ
      technique. These forages also were evaluated for RDP with the two enzyme
      concentrations identified in the first study, but incubation times were expanded
      to include 1, 2, 3, 4, and 5 h at the high concentration and 24, 30, 36, 42, 48,
      and 54 h at the low concentration. At the high enzyme concentration, r2
      statistics from linear regressions of enzymatic estimates of RDP on corresponding
      estimates obtained by the in situ procedure were high (r2 > or = 0.898) at all
      incubation times; in addition, slopes (range = 0.88 to 1.00) and intercepts
      (range = -9.4 to 3.5%) approached unity and 0, respectively. At the lower enzyme
      concentration, r2 statistics were still good (> 0.81), but slopes (0.59 to 0.67)
      and intercepts (18.5 to 21.9%) for all incubation times did not meet the
      respective goals of unity and 0.

PMID- 10068957
TI  - Ruminal escape, gastrointestinal absorption, and response of serum methionine to
      supplementation of liquid methionine hydroxy analog in dairy cows.
AB  - Availability of liquid methionine hydroxy analog [D,L-2-hydroxy-4-(methylthio)
      butanoic acid] was evaluated in two experiments using four cannulated lactating
      dairy cows. The first experiment was designed as a 4 x 4 Latin square. Each cow
      received a pulse dose of 0, 30, 60, or 90 g of the methionine analog in the rumen
      each day for 10 d. Duodenal samples were collected at 16, 20, and 24 h after
      dosing for the last 5 d and pooled. The methionine analog was not detected in
      duodenal contents because it passed rapidly from the rumen relative to the
      sampling protocol. In the second experiment, cows were offered 90 g of the
      methionine analog and 600 ml of Cr-EDTA (3.5 g of Cr) mixed with ground corn for
      a period of 20 min after which any remains of the treatment were placed in the
      rumen. The concentration of the analog peaked in ruminal and duodenal fluid at 1
      and 3 h, respectively. Based on the fractional rate constants for ruminal and
      duodenal disappearance of the methionine analog and passage of the liquid, it was
      determined that 50.0 +/- 2.8% of the methionine analog escaped ruminal
      degradation and became available for intestinal absorption (44.6 +/- 5.7%) or was
      absorbed from the omasum (5.4 +/- 3.3%). Serum methionine concentration peaked 6
      h after analog dosing at a level that was three times the predose level,
      indicating that the methionine analog that escaped ruminal degradation was
      absorbed and metabolized to methionine.

PMID- 10068958
TI  - Vascular sources of phenylalanine, tyrosine, lysine, and methionine for casein
      synthesis in lactating goats.
AB  - The contribution to casein biosynthesis of peptides derived from blood was
      examined in late lactation goats (254 to 295 d in milk). Ratios of mammary uptake
      of free amino acids (AA) in blood to output of AA in milk protein and ratios of
      the enrichments of Phe, Tyr, Met, and Lys at isotopic plateau in secreted milk
      casein to the free AA in arterial and mammary vein blood were monitored during
      the last 5 h of a 30-h continuous i.v. infusion of [1-13C]Phe, [2H4]Tyr, [5
      13CH3]Met, and [2-15N]Lys on two occasions: before (control) and on d 6 of an
      i.v. infusion of Phe (6 g/d). During the control, uptakes of free Phe and Met
      were less than their output in milk. This result was comparable with the labeling
      kinetic results, suggesting that vascular peptides contributed 5 to 11% of Phe
      and 8 to 18% of Met. Free Tyr and Lys uptakes during the control were sufficient
      for milk output; however, the labeling kinetics indicated that 13 to 25% of the
      Tyr and 4 to 13% of the Lys were derived from peptides. Infusion of Phe increased
      the uptake of free AA but reduced the contribution of peptides toward Phe (0 to
      3%) and Tyr (8 to 14%) supply for casein synthesis. Whole body hydroxylation of
      Phe to Tyr increased from 10 to 18% with the infusion of Phe; within the mammary
      gland, this conversion was lower (3 to 5%). Results suggest that the mammary
      utilization of peptides containing Phe and Tyr appears to depend on the supply of
      free AA in blood.

PMID- 10068959
TI  - Effects of grain source and enzyme additive on site and extent of nutrient
      digestion in dairy cows.
AB  - Four lactating, cannulated Holstein cows were used in a 4 x 4 Latin square design
      to investigate the effects of grain source and fibrolytic enzyme supplementation
      on ruminal fermentation, nutrient digestion in the rumen and in the intestine,
      and milk production. A 2 x 2 factorial arrangement was used; two grains (barley
      and hull-less barley) were combined with and without enzyme. The enzyme
      supplement (Pro-Mote; Biovance Technologies Inc., Omaha, NE) contained primarily
      cellulase and xylanase activities and was applied daily to the total mixed diet.
      Dry matter intake was not affected by diet, but starch intake was greatest when
      hull-less barley was fed. Starch from hull-less barley was more digestible in the
      rumen and in the total tract than was starch from barley, but opposite results
      occurred for fiber digestion, indicating that hull-less barley depressed fiber
      digestion. As a result, cows fed the hull-less barley diets tended to produce
      more milk with a higher milk lactose content than did cows fed the barley diets.
      Enzyme supplementation had minimal effects on ruminal digestion but increased
      nutrient digestibility in the total tract and the proportion of microbial N in
      nonammonia N. Consequently, cows fed diets supplemented with enzyme had a higher
      milk protein content and tended to produce more 4% fat-corrected milk than did
      control cows. These results indicate that the use of hull-less barley rather than
      barley increased the digestible energy intake of dairy cows, resulting in higher
      milk production. The use of a fibrolytic enzyme mixture enhanced feed
      digestibility and milk production.

PMID- 10068960
TI  - Effects of an enzyme feed additive on extent of digestion and milk production of
      lactating dairy cows.
AB  - A study was conducted using lactating Holstein cows with ruminal and duodenal
      cannulas in a 4 x 4 Latin square design to investigate fibrolytic enzyme
      supplementation on site and extent of nutrient digestion. The four diets
      consisted of 45% concentrate, 10% barley silage, and 45% cubed alfalfa hay (dry
      matter basis) and differed in enzyme supplementation: 1) control cubes, 2) cubes
      treated with 1 g of enzyme mixture/kg of cubes, 3) cubes treated with 2 g of
      enzyme mixture/kg of cubes, and 4) both concentrate and cubes treated with 1 g of
      enzyme mixture/kg of dry matter. The enzyme supplement contained primarily
      cellulase and xylanase activities. Digestion of organic matter and neutral
      detergent fiber in the total tract was higher for cows fed the high dosage of
      enzyme than for cows fed the control cubes. Ruminal digestibility of crude
      protein was higher, but that of organic matter and neutral detergent fiber was
      only numerically higher, for cows fed the high dosage of enzyme compared with
      that of cows fed the control cubes. Higher ruminal digestibility associated with
      the high dosage of enzyme resulted in more microbial protein synthesis. Milk
      production increased for cows fed the high dosage of enzyme compared with cows
      fed the control cubes and effects of the addition of enzyme on milk composition
      were minimal. The results demonstrated the benefits of using a fibrolytic enzyme
      additive to enhance feed digestion and milk production by dairy cows. The
      response to enzyme supplementation was affected more by amount of enzyme than by
      whether the enzyme was added to forage or concentrate.

PMID- 10068961
TI  - Performance and nutrient digestibility by dairy cows treated with bovine
      somatotropin and fed diets with steam-flaked sorghum or steam-rolled corn during
      early lactation.
AB  - This study compared effects of exogenous bovine somatotropin (bST) on the
      performance of early lactation cows fed diets differing in ruminally degradable
      starch. Thirty-two Holstein cows (24 multiparous) in early lactation (5 d in
      milk) were divided into four groups and fed diets containing 39% grain as steam
      flaked sorghum or steam-rolled corn with or without exogenous bST for 90 d. Grain
      processing did not affect dry matter intake as a percentage of body weight or
      yields of milk, but steam-rolled corn improved efficiency of feed utilization
      during the first 45 d of the study. Cows receiving bST had lower dry matter
      intake during the first 45 d of treatment. Milk yield and efficiency of feed
      utilization were increased by bST treatment, and milk yield response was greater
      during the first half than during the second half of the study. Milk composition
      and yield of milk components did not differ among treatments. Flaked sorghum
      increased in vitro starch hydrolysis and digestibilities of dry matter, organic
      matter, and starch, but neither method of grain processing nor bST affected
      digestibilities of crude protein, acid detergent fiber, or neutral detergent
      fiber. Grain type did not affect milk yield, and responses to bST were lower from
      7 to 13 wk than from 1 to 6 wk prepartum.

PMID- 10068962
TI  - Conjugated linoleic acid content of milk and cheese from cows fed extruded
      oilseeds.
AB  - Extruded oilseeds were fed to 24 dairy cows to study the influence on the
      conjugated linoleic acid content of milk and cheese. Cows were fed one of three
      diets that contained forage and grain in a ratio of 47:53. A control diet
      containing 13.5% soybean meal was compared with diets containing 12% full fat
      extruded soybeans or 12% full fat extruded cottonseed. The control, extruded
      soybean, and extruded cottonseed diets contained 2.73, 4.89, and 4.56% fatty
      acids, respectively. Measurements were made during the last 5 wk of the 8-wk
      experiment. The DM intakes and 3.5% fat-corrected milk yields were higher for
      cows fed the extruded soybean and extruded cottonseed diets than for cows fed the
      control diet. A tendency for lower fat and protein contents in the milk of cows
      fed the extruded soybean and extruded cottonseed diets was detected. Most of the
      C18 fatty acids were increased in the milk and cheese when extruded soybeans and
      cottonseeds were fed. The conjugated linoleic acid content in milk and cheese
      increased a mean of 109% when full fat extruded soybeans were fed and increased
      77% when cottonseeds were fed compared with the conjugated linoleic acid content
      when the control diet was fed. Processing the milk into cheese did not alter the
      conjugated linoleic acid content. The conjugated linoleic acid content of milk
      and cheese can be increased by the inclusion of full fat extruded soybeans and
      full fat extruded cottonseeds in the diets of dairy cows.

PMID- 10068963
TI  - Effect of ethanol in feed on milk flavor and chemical composition.
AB  - A crossover study was performed using 24 dairy cows to investigate whether pure
      ethanol in concentrations that could be found in well-fermented silages
      influenced milk composition or flavor. Cows were fed a standard ration of well
      fermented grass silage for ad libitum intake and high moisture barley and a
      protein concentrate in restricted amounts. A daily dose of ethanol (600 g) was
      divided into three meals/d and fed with grass silage. When cows received ethanol,
      milk yields decreased slightly, but milk fat and protein concentrations increased
      so that energy-corrected milk yield increased by 0.9 kg/d. Milk concentrations of
      lactose and urea decreased, concentrations of ethanol and acetone increased,
      concentrations of free fatty acids increased slightly, and alpha-tocopherol
      concentrations were unaffected. The proportion of palmitic acid in milk fat
      increased, and the proportion of unsaturated acids decreased. Organoleptic milk
      quality was reduced because of an increase in milk tainted by feed flavors. The
      off-flavor could not be attributed solely to the ethanol transmitted to the milk.
      Precautions should be taken to avoid extensive production of ethanol during
      fermentation of grass silage and other feeds that are to be fed to dairy cows.

PMID- 10068964
TI  - Significance of amount and form of dietary selenium on blood, milk, and casein
      selenium concentrations in grazing cows.
AB  - Organic selenized yeast enriched with selenoamino acids or inorganic sodium
      selenate (Na2SeO4) was administered per os three times weekly as a drench for 133
      d to previously unsupplemented cows that were grazing low Se pastures. Treatment
      groups received the equivalent of 2 or 4 mg of Se/d of either supplement form.
      Control cows did not receive a drench. Samples of blood and milk were collected
      regularly throughout the trial. Selenium concentrations in blood, milk, casein,
      and liver and glutathione peroxidase activity in blood and liver are reported as
      responses per milligram of Se intake. Mean blood Se concentrations in treated
      cows increased steadily and, by d 133, were 4.7 to 8.8 times that in controls.
      Selenized yeast was 2 to 3 times more effective than was Na2SeO4, and low Se
      intakes were 27% more efficient per milligram of Se administered than were high
      Se intakes at increasing milk Se concentration. Casein Se content mirrored that
      of milk; among all treated and control cows and throughout the trial, the molar
      ratio of Se in casein as a percentage of the Se in whole milk was constant at 71
      +/- 1.2%. The Se concentration in liver biopsies taken on d 133 was indicative of
      total Se intake during the trial and ranged from 920 to 3920 nmol of Se/kg of
      fresh weight. These results demonstrate the differing efficacy of organic and
      inorganic Se dietary supplements to increase dairy cow Se status and to enhance
      Se content of milk and casein.

PMID- 10068965
TI  - Comparison of test interval and best prediction methods for estimation of
      lactation yield from monthly, a.m.-p.m., and trimonthly testing.
AB  - A method with best prediction properties that condenses information from all test
      days into measures of lactation yield and persistency has been proposed as a
      possible replacement for the test interval method and projection factors. The
      proposed method uses previously established correlations between individual test
      days and includes inversion of a matrix for each lactation. Milk weights that
      were representative of monthly, a.m.-p.m., and trimonthly test plans were
      examined to compare the accuracy of best prediction and test interval methods for
      estimating lactation yield. Individual milk weights or daily yields of 658
      Canadian cows in 17 herds were selected to correspond to test intervals for
      100,000 US cows. For a.m.-p.m. testing, the initial milk weight that was credited
      was selected randomly from the a.m. or p.m. milking and was alternated
      thereafter. Trimonthly credits were from one of the first three designated test
      day weights, selected randomly, and each third designated test weight thereafter.
      Correlations between 305-d actual lactation yield and lactation estimates by the
      test interval method were 0.97, 0.96, and 0.93 for monthly, a.m.-p.m., and
      trimonthly testing, respectively. Corresponding correlations for the best
      prediction method were 0.97, 0.97, and 0.93. Standard deviations of differences
      between estimated and 305-d actual yields for monthly, a.m.-p.m., and trimonthly
      testing were 373, 400, and 546 kg, respectively, for best prediction regressed on
      herd mean, which was a reduction in estimation error of 4, 6, and 10% over the
      test interval method. The advantage of best prediction was moderate if two milk
      weights were recorded monthly and was larger if testing was less frequent.
      Advantages also were found for fat and protein yields estimated by multitrait
      best prediction for records with reduced component sampling.

PMID- 10068966
TI  - Results of a nationwide survey to determine feedstuffs fed to lactating dairy
      cows.
AB  - A nationwide survey to determine feedstuffs used in the diets of dairy cows was
      conducted. This survey was mailed to dairy nutritionists at universities in each
      state to describe the use of 144 feedstuffs. Twenty-eight states responded and
      were grouped by region as follows: Northeast (Maine, Maryland, New Hampshire, New
      York, Ohio, Vermont, and West Virginia), Northwest (Idaho, Oregon, and
      Washington), Midwest (Iowa, Illinois, Michigan, Minnesota, Missouri, Nebraska,
      North Dakota, South Dakota, and Wisconsin), Southeast (Florida, Georgia,
      Kentucky, South Carolina, Tennessee, and Virginia), and Southwest (Arizona,
      Oklahoma, and Texas). Comparisons of the feedstuffs most commonly fed, the
      maximum inclusion rate of feedstuffs in the diet, and how these feedstuffs were
      fed (alone or in a mixed diet) were made. The maximum percentage fed was also
      reported. Overall, concentrate feeds were fed blended with other ingredients more
      often (98.7% of the time) than forages (67.8% of the time). Also, forage was fed
      at a higher percentage (42.3%) of the total diet relative to individual
      concentrate ingredients (16.3%). Corn silage, soybean meal, corn grain, alfalfa
      hay, and grass hay were common feeds across all regions. However, the use of by
      product feeds was variable depending on local availability.

PMID- 10068967
TI  - Nitric oxide inhalation and use in treatment of ARDS.

PMID- 10068968
TI  - Anesthetic management of the patient with a pacemaker.
AB  - Anesthetic care depends on the patient underlying condition. Local anesthesia is
      preferable. Do not use heavy sedation. If you use GA avoid suxamethonium. If the
      PM was recently implanted, avoid N2O. During operation change to fixed-rate.
      Precautions for electrocautery. Post-operatively inform cardiologist to readjust
      the PM.

PMID- 10068969
TI  - Analgesic effects of intra-muscular ketoprofen (Profenid) and pethidine for
      squint surgery in children.
AB  - Administration of analgesics before surgery can decrease the intra-operative
      anesthetic requirement and pain during the early post-operative period (pre
      emptive analgesia). The objective of this study was to evaluate an intra-muscular
      preparation of ketoprofen as analgesic in mild to moderate pain in children. In a
      double-blind placebo-controlled study, 91 healthy ASA I or II children undergoing
      squint opthalmic surgery was undertaken in the Ophthalmic Services at King Abdel
      Aziz University Hospital Riyadh. The postoperative analgesic effects of intra
      muscular pethidine and ketoprofen, just after the induction of anesthesia were
      compared. Patients were randomized to receive ketoprofen (1 mg W kg-1), pethidine
      (1 mg W kg-1) or saline (0.1 ml W kg-1). Anesthesia was induced and maintained
      with halothane and nitrous oxide via a facemask. Post-operative pain was assessed
      by a blinded observer using an objective pain scale. Results revealed that the
      ketoprofen group had lower post-operative pain scores and required less frequent
      analgesic therapy in the early postoperative period compared to the pethidine and
      placebo groups. In contrast, there were no differences in pain scores or
      analgesic requirements between the pethidine and the placebo groups. It is
      concluded that the preoperative administration of intramuscular ketoprofen, but
      not pethidine, provided better postoperative pain control than placebo in
      children undergoing ophthalmic surgery.

PMID- 10068970
TI  - Anesthesia for laparoscopic general surgery. A special review.
AB  - Laparoscopy employs highly technical equipment, and the surgeon needs special
      training in the technique. He should master in-depth knowledge of the use of
      optics, electrical principles, gas under pressure, and the physiologic changes
      that occur when carbon dioxide is placed in the abdominal cavity. Above all, the
      surgeon must adhere rigidly to guidelines for appropriate technique, and
      deviation will most assuredly result in complications and even death. General
      surgery application of laparoscopy followed a wealth of medical experience from
      gynecological laparoscopies, which declared the technique as safe, reduced
      hospital stay with little pain and disfigurement. Laparoscopic cholecystectomy
      started to enjoy ever increasing popularity. It retained the advantages of
      shorter hospital stay, more rapid return to normal activities, less pain, small
      incisions and less postoperative ileus compared with the traditional open
      cholecystectomy. Soon many procedures were done using this new technique in
      adults and children. Anesthesia for laparoscopy has been established with a broad
      usage of agents and techniques. General anesthesia using balanced anesthesia
      technique including intravenous induction agents like: thiopentone, propofol,
      etomidate, and inhalational agents like nitrous oxide, isoflurane, desflurane,
      has been reported. Variety of muscle relaxants including succinylcholine,
      mivacurium, atracurium, vecuronium aiming at rapid recovery and cardiovascular
      stability. Total intravenous anesthesia using agnets like propofol, midazolam and
      ketamine, alfentanil and vecuronium has been reported also for outpatient
      laparoscopy. Epidural anesthesia was considered as safe alternative to general
      anesthesia for outpatient laparoscopy without associated respiratory depression.
      As for pain relief, many methods have been used. The pain mechanism is variable
      and analgesia requirement is less than those of open surgery. Cited complications
      include pneumothorax, cardiovascular collapse, surgical emphysema and pneumo
      peritoneum complications. Among the implication for anesthesia care, the
      importance of preoperative monitoring, careful positioning and observation during
      the insufflation of carbon dioxide. The drive to have short term admission to
      hospital would make it imperative to use short acting rapidly eliminated
      anesthetic drugs, avoidance of vomiting and pain by proper use of modern anti
      emetics and NSAID to help in avoidance of narcotics or reduction of the
      requirement.

PMID- 10068971
TI  - Anesthesia for laparoscopic gastroplasty in morbid obesity.

PMID- 10068972
TI  - Use of propofol and sevoflurane in moyamoya disease--case reports and literature
      review.

PMID- 10068973
TI  - Successful treatment of near fatal thromboembolism--a case report.

PMID- 10068974
TI  - Anesthesia for multiple sclerosis in a patient undergoing correction of ASD--a
      case report.

PMID- 10068975
TI  - Delayed asystole following spinal anesthesia--a case report.

PMID- 10068976
TI  - Amphotericin B and cardiac toxicity--a case report.

PMID- 10068977
TI  - [Lead poisoning in the newborn and infants: an epidemiological study in an area
      of Northern Italy].
AB  - OBJECTIVE: Lead crosses the placenta and can cause permanent neurological
      impairment by prenatal poisoning. Blood lead levels higher than 10 mcgr/dl in
      children age 1 to 2 years may be toxic. In 1991 the CDC (Centers for Disease
      Control and Prevention) published "Preventing Lead Poisoning in Young Children"
      with the new guidelines defining the value of 10 mcgr/dl as the security limit.
      Since no blood lead levels in childhood have been collected in Italy this study
      reports blood lead levels in newborns and 4 month old infants in the Piemonte
      Region. DESIGN: The study was carried out on a random sample of 55 mother-infant
      couples attending the Mauriziano Hospital in Turin. The cohort was divided into
      urban versus rural residence. In every subject attending the study lead, ALA-d
      and Zn-PP were measured on venous blood specimens in three different moments.
      RESULTS: Even though our study refers to a small population our data were
      reassuring. The mean lead values found in the cohort in the three different
      stages were all below 10 mcgr/dl. ALA-d and Zn-PP resulted also in normal ranges.
      No statistical difference emerged between urban and rural coming subjects.
      CONCLUSIONS: In consideration of the results obtained we cannot confirm the
      necessity of a general screening programme for lead poisoning in our population.
      We assert the utility of a selective screening on the basis of a questionnaire as
      already experimented in some states of the U.S.A.

PMID- 10068978
TI  - [Partial liquid ventilation (PLV) in the newborn and infants: initial experiences
      in Italy].
AB  - Partial liquid ventilation is a valid alternative ventilation strategy for the
      management of the respiratory distress in newborn and infant. Authors describe
      their first experiences in 11 children (7 newborns, 4 infants).

PMID- 10068979
TI  - [Discontinuing of antiepileptic therapy].
AB  - The merits of suspending the treatment of children suffering from epilepsy must
      be evaluated under a number of different headings. It may be justified in the
      light of side effects brought about by the drugs administered, or on the basis of
      a favourable prognosis that often characterises these form of epilepsy. The
      current tendency is to start reducing the dosage of drugs 2-3 years after the
      complete remission of the seizures, fully suspending treatment 6-12 months
      thereafter. Greater prudence is called for in cases where the containment of
      seizures has proved particularly problematic. Despite these precautions, relapses
      have been found to occur in 15-30% of patients, during both the reduced dosage
      period and once treatment has been discontinued (normally within the first year).
      Subjects with brain injury and those effected by particular forms of epilepsy
      (myoclonic epilepsy, grand and petit mal status, complex epileptic attacks) are
      more prone to relapse, particularly when seizures have been very frequent.
      Adolescence and, according to many Authors, persistent EEG alterations, also
      represent negative factors. In most cases, seizures can be controlled once
      treatment is resumed. In all cases, the problems associated with the withdrawal
      of anti-epileptic treatment must be discussed carefully with the patient and his
      or her family; an attempt should be made to identify the risks involved and the
      patient must be followed closely during the delicate discontinuance period.

PMID- 10068980
TI  - [Helicobacter pylori. I. Morphology, biochemistry, antigenic profile and
      correlated diseases].
AB  - Infection by Helicobacter pylori (HP) occurs all over the world and is related to
      the socio-economic development of the subject's country of residence and age.
      Various strains of HP can be identified on the basis of the microbiological
      characteristics of the bacterium and, in particular, or its antigenic profile,
      while the virulence factors are responsible for the damage that HP can cause. The
      virulence factors include components (flagellum and adhesin) and substances
      produced by bacterium (enzymes and cytotoxins), the most important among which
      are urease and the cytotoxins, CagA and VacA. It is the association of these
      virulence factors that is responsible for the different pathologies to which HP
      positive subjects are prone. The link between HP and gastritis, peptic ulcer and
      gastric cancers (adenocarcinoma and lymphoma) is now proven. Whether there is a
      link between HP and RAP in young children is still a matter for debate; some
      Authors claim that there is, while others refute it.

PMID- 10068981
TI  - [Prevalence of Chlamydia pneumoniae in respiratory infections in children: an
      ambulatory diagnostic problem].
AB  - It has been recently suggested that Chlamydia Pneumoniae infection is a common
      finding among children with acute respiratory diseases. Chlamydia cell culture is
      difficult and time-consuming to perform. Polymerase chain reaction (PCR) is a
      more rapid but also more expensive technique used to identify Chlamydia in
      pharyngeal swab, but it can be performed only in few specialized laboratories. We
      tested a rapid enzyme immuno-assay to detect Chlamydia in 20 children with
      respiratory infections (mean age 3.29 years; male:female ratio = 12:8) and in 21
      healthy children (mean age 4.70 years male:female ratio = 15:6). Prevalence of
      Chlamydia isolation from pharyngeal swab was very high in both patients and
      healthy children without a significative difference in the two considered groups
      (45% vs 42%, p = 0.8). Specific Chlamydia IgG antibodies were undetectable in all
      patients and healthy children. Nine out of 20 patients affected by acute
      respiratory disease were Chlamydia-positive and 11 out 20 were Chlamydia
      negative: these two groups didn't differ in regard to clinical and laboratory
      features, whereas duration of symptoms was significantly longer in Chlamydia
      positive patients (9.3 vs 5.5 days, p = 0.014). Our study suggests a high
      prevalence of Chlamydia pharyngeal swab positivity in both healthy and sick
      children. Diagnosis of Chlamydia infection was not feasible on the basis of the
      considered clinical and laboratory findings.

PMID- 10068982
TI  - [Nephroblastoma and polycystic dysplastic kidney].
AB  - The Authors pass on the case of a nephroblastoma, associated to Wilms Tumorlet
      and combined nephroblastomatosis, arose on a multicystic dysplastic kidney. They
      examine the relationships between the nephroblastoma and the kidney
      malformations, the possibility of malignant degeneration of a multicystic
      dysplastic kidney and the necessity of the nephrectomy as a prevention of the
      degeneration. At the moment the statistic data don't justify the nephrectomy a
      the birth to prevent the arising of a nephroblastoma.

PMID- 10068983
TI  - [Nephroblastoma presenting with massive hematuria may require emergency surgery].
AB  - About 20% of children with nephroblastoma at onset present with macroscopic
      haematuria, which is usually asymptomatic and of little clinical relevance. The
      Authors describe an unusual case of nephroblastoma presenting with massive
      haematuria causing extensive blood clothing along the urinary tract and bladder.
      The phenomenon was of such entity to determine urinary retention and induce
      performing emergency nephrectomy. Tumour resection was radical and postoperative
      course uneventful. Eighteen months after surgery patient is in excellent status
      and full remission.

PMID- 10068984
TI  - [Ceftriaxone-induced cholelithiasis].
AB  - The formation of biliary sludge and cholelithiasis after ceftriaxone
      administration is not uncommon. Prompt resolution of sludge has been demonstrated
      with discontinuation of the drug. Despite this, cholecystectomy has been
      performed in symptomatic patients. Ceftriaxone is popular drug in pediatrics, but
      the complication is not widely appreciated in the gastroenterology and surgical
      literature. For this adverse effect and for cost ceftriaxone should be used with
      more caution. We describe two cases of children with ceftriaxone induced
      cholelithiasis.

PMID- 10068985
TI  - [Adhesion of the labia minora in children].
AB  - Vulvar agglutination or vulva connivens in childhood is a common disease and an
      important source of anxiety for parents. The Authors report on the anatomic
      classification, the etiology and the prevalence of this genital anomaly in the
      pediatric age. In the 2021 patients of our series examined in the Department of
      Pediatrics in Poggibonsi and in the Department of Pediatric Surgery of the
      University of Siena during a period of 7 years and revisited in the period
      between January 1995 and December 1996 (follow-up: max 7 years) no cases were
      observed in the first month of life (793 newborn infants) and this fact might
      help to exclude a congenital origin. The incidence of vulvar agglutination in
      1228 children was 9.8%; in the 3.6% of cases vulvar agglutination was complete,
      while in the 6.1% it was incomplete. 60% of complete vulvar adhesions were in 3-6
      years old patients, while the incomplete one was prevalent during the first 3
      years of life. In our series vulvar adhesion was more common than in other
      studies, but the Author report no cases of correlated urinary or genital
      infections. It is important to reassure parents and to maintain a conservative
      approach to this anomaly. Estrogen therapy in this study was applied only in a
      few cases, because almost all the patients healed before puberty; the surgical
      division was applied only in case of recurrence.

PMID- 10068986
TI  - [Gastroduodenal stress ulcer. A pediatric case report].
AB  - The Authors describe a case of a post rubella encephalitis in a six year old
      child complicated by severe haemorrhagic episodes due to a duodenal stress ulcer.
      Despite H2 receptors antagonist therapy, surgery has been required to control the
      repeated bleeding episodes.

PMID- 10068987
TI  - [Description of a case of spondylo-thoracic dysplasia or Jarcho-Levin syndrome].
AB  - A case of Jarcho-Levin Syndrome is described which is characterized by severe
      costo-vertebrate anomalies. In our case signal severe cardiopathy.

PMID- 10068988
TI  - Sensitivity, cooperativity and gain in chemotaxis signal transduction.

PMID- 10068989
TI  - Ushers and other doorkeepers.

PMID- 10068990
TI  - Treponema pallidum: doing a remarkable job with what it's got.

PMID- 10068991
TI  - Exploring parasite genomes.

PMID- 10068992
TI  - The role of CD1-restricted T cells in infectious diseases.

PMID- 10068993
TI  - Throwing the switch in bacterial chemotaxis.
AB  - In Escherichia coli chemotaxis, the switch from counterclockwise to clockwise
      rotation of the flagella occurs as a result of binding of the phosphorylated CheY
      protein to the base of the flagellum. Analysis of CheY variants has provided a
      picture of the surface of CheY that undergoes conformational shifts, as a result
      of phosphorylation, to interact directly with the flagellum. Whether phospho-CheY
      binding and flagellar switching are sequential steps or can occur in a concerted
      fashion has yet to be determined.

PMID- 10068994
TI  - T-cell transformation by Marek's disease virus.
AB  - Marek's disease virus (MDV) is an avian herpesvirus that causes rapid development
      of T-cell lymphomas in chickens. The MDV genes currently thought to be involved
      in lymphomagenesis include a bZIP transactivator that is homologous to fos and
      jun oncogenes but do not appear to have counterparts in other oncogenic
      herpesviruses.

PMID- 10068995
TI  - Escherichia coli mutator genes.
AB  - The isolation and characterization of Escherichia coli mutator genes have led to
      a better understanding of DNA replication fidelity mechanisms and to the
      discovery of important DNA repair pathways and their relationship to spontaneous
      mutagenesis. Mutator strains in a population of cells can be beneficial in that
      they allow rapid selection of variants during periods of stress, such as drug
      exposure.

PMID- 10068996
TI  - Small RNAs in Escherichia coli.
AB  - Bacterial cells contain several small RNAs (sRNAs) that are not translated. These
      stable, abundant RNAs act by multiple mechanisms, such as RNA-RNA basepairing,
      RNA-protein interactions and intrinsic RNA activity, and regulate diverse
      cellular functions, including RNA processing, mRNA stability, translation,
      protein stability and secretion.

PMID- 10068997
TI  - Unexplored reservoirs of pathogenic bacteria: protozoa and biofilms.
AB  - In the natural, industrial, hospital and domestic environments, there are
      numerous phenotypes of pathogenic microorganisms, which vary considerably in
      chemical, physical and biological properties. A link exists between survival,
      resistance and virulence. In particular, surface-adherent biofilms and bacteria
      living within protozoa pose potential health problems that are unrecognized by
      conventional laboratory culture methods.

PMID- 10068998
TI  - Cell cycle transition in early embryonic development of Xenopus laevis.
AB  - This article reviews cell cycle changes that occur during midblastula transition
      (MBT) in Xenopus laevis based on research carried out in the authors' laboratory.
      Blastomeres dissociated from the animal cap of blastulae, as well as those in an
      intact embryo, divide synchronously with a constant cell cycle duration in vitro,
      up to the 12th cell cycle regardless of their cell sizes. During this synchronous
      cleavage, cell sizes of blastomeres become variable because of repeated unequal
      cleavage. After the 12th cell cycle blastomeres require contact with an
      appropriate protein substrate to continue cell division. When nucleocytoplasmic
      (N/C) ratios of blastomeres reach a critical value during the 13th cycle, their
      cell cycle durations lengthen in proportion to the reciprocal of cell surface
      areas, and cell divisions become asynchronous due to variations in cell sizes.
      The same changes occur in haploid blastomeres with a delay of one cell cycle.
      Thus, post-MBT cell cycle control becomes dependent not only on the N/C relation
      but also on cell surface activities of blastomeres. Unlike cell cycle durations
      of pre-MBT blastomeres, which show monomodal frequency distributions with a peak
      at about 30 min, those of post-MBT blastomeres show polymodal frequency
      distributions with peaks at multiples of about 30 min, suggesting 'quantisement'
      of the cell cycle. Thus, we hypothesised that MPF is produced periodically during
      its unit cycle with 30 min period, but it titrates, and is neutralized by, an
      inhibitor contained in the nucleus in a quantity proportional to the genome size;
      however, when all of the inhibitor has been titrated, excess MPF during the last
      cycle triggers mitosis. At MBT, cell cycle checkpoint mechanisms begin to
      operate. While the operation of S phase checkpoint to monitor DNA replication is
      initiated by N/C relation, the initiation of M phase checkpoint operation to
      monitor chromosome segregation at mitosis is regulated by an age-dependent
      mechanism.

PMID- 10068999
TI  - Cytoplasmic factors that control nuclear behavior in mammalian oocytes: a re
      evaluation of studies performed as a student of Yoshio Masui.
AB  - Studies performed by the author in the laboratory of Dr Yoshio Masui are reviewed
      and interpreted in the light of subsequent findings. The first series of studies
      indicated that that chromosome condensation during meiotic maturation of mouse
      oocytes is controlled initially by a stable protein that decays during maturation
      and subsequently by an unstable protein synthesized after germinal vesicle
      breakdown. Cyclin B is present in immature oocytes, becomes partially degraded
      near metaphase I and then re-accumulates, suggesting that this may be protein
      whose activity was inferred from the original results. The second series of
      experiments indicated that factors which appear in the oocyte cytoplasm during
      maturation are able to remodel the sperm into metaphase-like chromosomes, and
      that the supply of these factors is limited. Recent work indicates that these
      factors are required for the assembly of histones onto the sperm DNA, and has
      identified two molecular species, mNAP-1 and NPM-3, known to promote replication
      independent chromatin assembly in somatic cells, that are expressed in oocytes.

PMID- 10069000
TI  - Autonomous activation of histone H1 kinase, cortical activity and microtubule
      organization in one- and two-cell mouse embryos.
AB  - The activation of M-phase promoting factor (MPF) in one-cell mouse embryo is
      independent from the nucleus. Other autonomous phenomena include the cortical
      activity observed at the end of the first cell cycle and the reorganization of
      the microtubule network. Here, we observed that the autonomous control of MPF
      activation is present also in two-cell mouse embryos (H1 kinase activity being
      higher in the first than in the second cell cycle). Moreover, the disappearance
      of the cortical activity in anucleated halves is observed when MPF activation
      takes place. The rounding up of the cytoplast and the mitotic reorganization of
      the microtubule network correlates with the maximum activity of H1 kinase in
      anucleated halves from one-cell embryos. In anucleated halves of two-cell stage
      blastomeres neither the cortical activity nor the microtubule reorganization were
      observed. The degree of activation of histone H1 kinase, and, as a consequence,
      the cortical activity and the microtubule reorganization, does not depend on the
      distribution of cyclin B. Finally, the level of cyclin B synthesis is similar in
      anucleated and nucleated halves derived from both one- and two-cell embryos.

PMID- 10069001
TI  - Mos-induced p42 mitogen-activated protein kinase activation stabilizes M-phase in
      Xenopus egg extracts after cyclin destruction.
AB  - Previously, we have shown that the addition of a constitutively-active mitogen
      activated protein kinase kinase protein (MAPKK = MEK) to cycling Xenopus egg
      extracts activates the p42MAPK pathway, leading to a G2 or M-phase cell cycle
      arrest. The stage of the arrest depends on the timing of p42MAPK activation. If
      p42MAPK is activated prior to M-phase, or after exit from M-phase, the extract is
      arrested in G2. If p42MAPK is activated during entry into M-phase, the extract is
      arrested in M-phase. In this study, we show that the addition of recombinant Mos
      protein (which directly phosphorylates and activates MEK) to cycling egg extracts
      has the same effect as those described for MEK. The addition of Mos to the
      extract at the start of incubation leads to a G2 arrest with large interphase
      nuclei with intact nuclear envelopes. If Mos is added at later times, however,
      the activation of p42MAPK leads to an M-phase arrest with condensed chromosomes
      and mitotic arrays of microtubules. Moreover, the extent of M-phase specific
      phosphorylations is shown by the sustained presence of phosphoproteins that are
      detected by the monoclonal antibody MPM-2. Unexpectedly, in certain M-phase
      arrested extracts, histone H1 kinase activity levels reach a peak on entry into M
      phase but then fall abruptly to interphase levels. When these extracts are
      analyzed by immunoblotting, Cyclin B2 is destroyed in those samples containing
      low maturation promoting factor activity (MPF, cyclin B/Cdc2), yet chromosomes
      remain condensed with associated mitotic arrays of microtubules and M-phase
      specific phosphorylations are sustained. These results suggest that although MPF
      is required for entry into M-phase, once established, M-phase can be maintained
      by the p42MAPK pathway after the proteolysis of mitotic cyclins.

PMID- 10069002
TI  - Ras family proteins: new players involved in the diplotene arrest of Xenopus
      oocytes.
AB  - Oogonia undergo numerous mitotic cell cycles before completing the last DNA
      replication and entering the meiotic prophase I. After chromosome pairing and
      chromatid exchanges between paired chromosomes, the oocyte I remains arrested at
      the diplotene stage of the first meiotic prophase. Oocyte growth then occurs
      independently of cell division; indeed, during this growth period, oocytes (4n
      DNA) are prevented from completing the meiotic divisions. How is the prophase
      arrest regulated? One of the players of the prophase block is the high level of
      intracellular cAMP, maintained by an active adenylate cyclase. By using lethal
      toxin from Clostridium sordellii (LT), a glucosyltransferase that glucosylates
      and inactivates small G proteins of the Ras subfamily, we have shown that
      inhibition of either Ras or Rap or both proteins is sufficient to release the
      prophase block of Xenopus oocytes in a cAMP-dependent manner. The implications of
      Ras family proteins as new players involved in the prophase arrest of Xenopus
      oocytes will be discussed here.

PMID- 10069003
TI  - The legacy of lithium effects on development.
AB  - The simple element lithium causes specific effect on early embryonic development.
      In amphibians, treatment during early cleavage enhances anterior and dorsal
      development at the expense of posterior and ventral development. Conversely,
      treatment at late cleavage reduces head development. While an effect of lithium
      on the phosphoinositide cycle was suspected, the enhancement of dorsoanterior
      development is now thought to result primarily from stimulation of the Wnt/beta
      catenin pathway. The multiple uses of this pathway in development may account for
      lithium's various specific effects.

PMID- 10069004
TI  - Nuclear responses to MPF activation and inactivation in Xenopus oocytes and early
      embryos.
AB  - The cell cycle of most organisms is highlighted by characteristic changes in the
      appearance and activity of the nucleus. Structural changes in the nucleus are
      particularly evident when a cell begins to divide. At this time, the nuclear
      envelope is disassembled, the chromatin condenses into metaphase chromosomes, and
      the chromosomes associate with a newly formed spindle. Upon completion of cell
      division the nuclear envelope reassembles around the chromosomes as they form
      telophase nuclei, and subsequently interphase nuclei, in the daughter cells. The
      cytoplasmic control of nuclear behavior has been the theme of Yoshio Masui's
      research for much of his career. His pioneering demonstration that the cytoplasm
      of maturing amphibian oocytes causes the resumption of the meiotic cell cycle
      when it is injected into an immature oocyte provided unequivocal evidence that a
      cytoplasmic factor could initiate the transition from interphase to metaphase (M
      phase) in intact cells. As described in several reviews in this and the previous
      issue of Biology of the Cell (see Beckhelling and Ford; Duesbery and Vande Woude;
      Maller), Masui initially called this activity maturation promoting factor (MPF),
      but when it was realized that it was a ubiquitous regulator of both mitotic and
      meiotic cell cycles, MPF came to stand for M-phase promoting factor. Biochemical
      evidence indicates that MPF activity is composed of a mitotic B-type cyclins and
      cyclin-dependent kinase 1. The increase in the protein kinase activity of cdk1
      initiates the changes in the nucleus associated with oocyte maturation and with
      the entry into mitosis. This article will attempt to provide a brief summary of
      the responses of the nucleus to the activation of MPF. In addition, the effect of
      MPF inactivation on nuclear envelope assembly at the end of mitosis will be
      discussed. This article is written as a tribute to Yoshio Masui on his retirement
      from the University of Toronto, and as an expression of gratitude for his
      guidance while I was a student in his laboratory. I have felt very privileged to
      have known him as a mentor and a friend.

PMID- 10069006
TI  - The 1997 list. Proposed new bacterial taxa and proposed changes of bacterial
      names published during 1997 and considered to be of interest to medical or
      veterinary bacteriology (an informational note).
AB  - A list of names published or validated in 1997 is presented. We also comment on
      the tendency to base names of new taxa on a single bacterial strain, and the
      consequences for reliable descriptions that this tendency implies.

PMID- 10069005
TI  - Colicins--exocellular lethal proteins of Escherichia coli.
AB  - Colicins are toxic exoproteins produced by bacteria of colicinogenic strains of
      Escherichia coli and some related species of Enterobacteriaceae, during the
      growth of their cultures. They inhibit sensitive bacteria of the same family.
      About 35% E. coli strains appearing in human intestinal tract are colicinogenic.
      Synthesis of colicins is coded by genes located on Col plasmids. Until now more
      than 34 types of colicins have been described, 21 of them in greater detail, viz.
      colicins A, B, D, E1-E9, Ia, Ib, JS, K, M, N, U, 5, 10. In general, their
      interaction with sensitive bacteria includes three steps: (1) binding of the
      colicin molecule to a specific receptor in the bacterial outer membrane; (2) its
      translocation through the cell envelope; and (3) its lethal interaction with the
      specific molecular target in the cell. The classification of colicins is based on
      differences in the molecular events of these three steps.

PMID- 10069007
TI  - In vivo and in vitro cloning and phenotype characterization of tellurite
      resistance determinant conferred by plasmid pTE53 of a clinical isolate of
      Escherichia coli.
AB  - A determinant encoding resistance against potassium tellurite (Te(r)) was
      discovered in a clinical isolate of Escherichia coli strain KL53. The strain
      formed typical black colonies on solid LB medium with tellurite. The determinant
      was located on a large conjugative plasmid designated pTE53. Electron-dense
      particles were observed in cells harboring pTE53 by electron microscopy. X-Ray
      identification analysis identified these deposits as elemental tellurium and X
      ray diffraction analysis showed patterns typical of crystalline structures.
      Comparison with JCPDS 4-0554 (Joint Committee on Powder Diffraction Standards)
      reference data confirmed that these crystals were pure tellurium crystals. In
      common with other characterized Te(r) determinants, accumulation studies with
      radioactively labeled tellurite showed that reduced uptake of tellurite did not
      contribute to the resistance mechanism. Tellurite accumulation rates for E. coli
      strain AB1157 harboring pTE53 were twice higher than for the plasmid-free host
      strain. In addition, no efflux mechanism was detected. The potassium tellurite
      resistance determinant of plasmid pTE53 was cloned using both in vitro and in
      vivo techniques in low-copy-number vectors pACYC184 and mini-Mu derivative pPR46.
      Cloning of the functional Te(r) determinant into high-copy cloning vectors pTZ19R
      and mini-Mu derivatives pBEf and pJT2 was not successful. During in vivo cloning
      experiments, clones with unusual "white colony" phenotypes were found on solid LB
      with tellurite. All these clones were Mucts62 lysogens. Their tellurite
      resistance levels were in the same order as the wild type strains. Clones with
      the "white" phenotype had a 3.6 times lower content of tellurium than the
      tellurite-reducing strain. Transformation of a "white" mutant with a recombinant
      pACYC184 based Te(r) plasmid did not change the phenotype. However, when one
      clone was cured from Mucts62 the "white" phenotype reverted to the wild-type
      "black" phenotype. It was suggested that the "white" phenotype was the result of
      an insertional inactivation of an unknown chromosomal gene by Mucts62, which
      reduced the tellurite uptake.

PMID- 10069008
TI  - Overexpression of the FNR protein of Escherichia coli with T7 expression system.
AB  - We have used the T7 expression system for expression of E. coli FNR protein. The
      fnr gene was cloned from its initiation codon ATG into the NdeI site of an
      expression vector and filamentous phage mGP1-2 was used as a donor of T7 RNA
      polymerase gene. The level of FNR expression attained by this expression
      arrangement was about 45% of total cell proteins.

PMID- 10069009
TI  - The Streptomyces aureofaciens homologue of the whiB gene is essential for
      sporulation; its expression correlates with the developmental stage.
AB  - In previous experiments, a Streptomyces aureofaciens gene highly similar to the
      sporulation-specific whiB gene of Streptomyces coelicolor was identified. By
      integrative transformation, via double cross-over, a stable null mutant of the
      whiB-homologous gene of S. aureofaciens was obtained. The disruption blocked
      differentiation at a stage between the formation of aerial mycelium and the
      development of mature spores, producing white aerial hyphae without septation.
      Expression of the whiB gene was investigated during differentiation by S1
      nuclease mapping, using RNA prepared from S. aureofaciens in various
      developmental stages. Two putative promoters were identified upstream of the whiB
      coding region. The stronger promoter, whiB-P2, was induced at the beginning of
      aerial mycelium formation, and the weaker promoter, whiB-P1, was expressed fairly
      constantly during differentiation. No differences in the expression of the whiB
      promoters were detected in an rpoZ-disrupted S. aureofaciens strain. The promoter
      bearing DNA fragment was inserted into the promoter-probe vector pARC1 to produce
      an expression pattern consistent with the results of direct RNA analysis.

PMID- 10069010
TI  - Substrate-dependent cadmium toxicity affecting energy-linked K+/86Rb transport in
      Staphylococcus aureus.
AB  - Bacteria accumulate high amounts of potassium in the cytoplasm. For studying
      transport of K+ (with 86Rb as a marker) in bacteria (Staphylococcus aureus
      17810S), the cells were depleted of the internal K+ pool by a DNP treatment.
      Kinetics and energetics of 86Rb transport was assayed with glucose as an
      exogenous energy source. It was shown that 86Rb uptake proceeded via a low
      affinity K+ transport system with an apparent K(m) of 2.3 mmol/L Rb+. Studies
      with the lipophilic cation TPP+ (tetraphenylphosphonium), the protonophore CCCP
      (carbonyl cyanide 3-chlorophenylhydrazone) and inhibitors (HQNO--2-heptyl-4
      hydroxyquinoline N-oxide; iodoacetate) indicated that 86Rb transport was driven
      by delta psi (membrane potential) generated via the respiratory chain. The effect
      of Cd2+ on 86Rb transport was assayed with two energy donors--glucose and L
      lactate. It was found that Cd2+ strongly inhibited delta psi-dependent 86Rb
      transport energized by cadmium-sensitive glucose oxidation, but was not toxic
      when cadmium-insensitive L-lactate was used as an energy source. The mechanism of
      these differential, substrate-dependent effects of Cd2+ on 86Rb transport is
      discussed.

PMID- 10069011
TI  - Extracellular acidification by Saccharomyces cerevisiae in normal and in heavy
      water.
AB  - Titratable acidity of the extracellular medium was compared with that calculated
      from pH changes in a suspension of Saccharomyces cerevisiae. After addition of
      cells to normal water the ratio of titratable acidity to the computed one was
      about 25, after addition of 50 mmol/L D-glucose it was about 13, after subsequent
      addition of K+ ions it was only 2. In heavy water the respective values were 30,
      9, and 1. Apparently, the principal buffer-generating processes have to do with
      glucose metabolism but little with the K+/H+ exchange observed after addition of
      K+. D2O appears to block processes producing the buffering capacity of the
      medium, among them possibly extrusion of organic acids.

PMID- 10069012
TI  - Molds on house walls and the effect of their chloroform-extractable metabolites
      on the respiratory cilia movement of one-day-old chicks in vitro.
AB  - The ciliostatic activity of the chloroform-extractable endo- and exometabolites
      of 5 strains of filamentous fungi--Alternaria sp., Aspergillus glaucus group,
      Aspergillus versicolor, Cladosporium sphoerospermum, Penicillium sp. and
      Ulocladium sp.--isolated from molded walls of a dwelling--on tracheal cilia from
      1-d-old chicks in vitro was evaluated. Endometabolites of Alternaria sp. and A.
      versicolor and exometabolites of Ulocladium sp. were the most active, these
      extracts stopped the ciliary movement within 1 d. The results are discussed in
      relation to the health status of people living in "moldy" dwellings.

PMID- 10069013
TI  - Type I beta-lactamases of Enterobacter cloacae and resistance to beta-lactam
      antibiotics.
AB  - The interaction of type-I beta-lactamases from Enterobacter cloacae with diverse
      beta-lactam compounds was examined. The ability of penicillin and cefoxitin to
      induce beta-lactamase production in this strain was assessed. The effect of beta
      lactamase inhibitors was measured on beta-lactamase extracts and on intact cells.
      E. cloacae 78 strain is a stably derepressed mutant showing limited
      susceptibility to a number of antibiotics except imipenem. Imipenem would
      therefore be the appropriate choice for therapy of infections caused by stably
      derepressed mutants of Enterobacter sp. producing type-I beta-lactamases.

PMID- 10069014
TI  - Arthritogenicity of Yersinia enterocolitica O:8 in hamsters: analysis of the
      immune response.
AB  - An animal model, hamster, was used for the study of Yersinia-induced arthritis.
      The development of arthritis, estimated by measuring the inflammation on hind
      paws after infection, was correlated with the kinetics of the immune response.
      Histological and immunofluorescence (IFI) studies and serum antibody measurements
      were performed. Two inflammatory peaks were observed: an acute one on day 11 post
      infection (p.i.) and a chronic one on days 26-35 p.i. Joint cultures were
      positive until day 14 p.i. IFI was used to demonstrate the deposit of bacterial
      antigens in the joint. A persistent response of cellular extract-specific IgG
      antibodies was observed until day 94. Lipopolysaccharide-specific IgG was
      statistically significant on day 26 p.i. Antibodies against bands 66 and 54 were
      observed by immunoblotting. Polyclonal activation was detected during reactive
      arthritis. It is shown that Y. enterocolitica is arthritogenic in hamsters,
      immune mechanisms participating in the development of this disease.

PMID- 10069015
TI  - Salmonellosis: lessons drawn from a germ-free pig model.
AB  - The germ-free pig model is shown to be useful for studying salmonellosis. The
      immune status of germ-free and infected gnotobiotic piglets is described. The
      regulatory role of cytokine is discussed and compared with our experimental
      findings.

PMID- 10069016
TI  - Detection of antigens in mycelial and in arthroconidial phases of Trichophyton
      mentagrophytes.
AB  - Protein pattern changes were investigated in the filamentous fungus Trichophyton
      mentagrophytes during the morphological transition induced by increased
      temperature and higher CO2 partial pressure in cultivation atmosphere. The
      differences between the mycelial and the arthroconidial phase were characterized
      by SDS-PAGE and by immunodetection with mouse polyclonal antibodies. The
      components found by Western blotting in mycelia were 88, 86, 32, 29, 19.5, 18.5
      kDa, in arthroconidia 108, 92, 88, 66, 56, 41, 39, 19.5 kDa. The results suggest
      the participation of some heat shock associated proteins of T. mentagrophytes in
      host immune response against mycotic infection.

PMID- 10069017
TI  - Characterization of Shigella dysenteriae type 1 capsular polysaccharide by
      immunochemical methods.
AB  - We have isolated the capsular polysaccharide from the strain of Shigella
      dysenteriae type 1 8337. The product was purified by ultracentrifugation, treated
      with enzymes (proteinase K, DNA-RNAase) and analyzed by immunochemical methods.
      Polyclonal antibodies were obtained from rabbits immunized by whole cell antigens
      prepared from Shigella by ultrasonic treatment and by purified capsular
      polysaccharide. Crossed immunoelectrophoresis, PAGE and Western blot analysis
      showed that this product containing mainly the polysaccharide component also
      contained glycoprotein and lipopolysaccharide. Double diffusion in agarose gel
      confirmed that the capsular preparation contained at least three antigens
      reacting with rabbit polyclonal antiserum.

PMID- 10069018
TI  - A case of fatal salt water intoxication following an exorcism session.
AB  - In response to a recent article published in this review, we present in this
      paper, an unusual case of fatal salt water intoxication. In this case, we point
      out three special features, the type of water ingested, the physiopathologic
      consequences of the ingestion and the very strange context of occurrence. This
      complex case allows us to point out complications due to salt poisoning and
      others caused by water intoxication.

PMID- 10069019
TI  - A one-step fluorescent detection method for lipid fingerprints; Eu(TTA)3.2TOPO.
AB  - This paper describes the development of a one-step fluorescent lipid reagent that
      involves europium chelates whose generic formula can be represented as
      europium(organic ligand)3.2(synergic reagent). An optimized formulation is
      presented and a comparison with physical developer was conducted which showed the
      new technique to be very good when fresh fingerprints were recovered but inferior
      to physical developer on aged prints (over a week). In addition, the
      compatibility of the technique with sequential methods such as ninhydrin and DFO
      is reported. The experimentation, results and chemical formulation of this study
      were presented to delegates of the International Symposium on Fingerprint
      Detection and Identification held in Israel in June 1995. Prior to that a patent
      application had been made.

PMID- 10069020
TI  - Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary
      tool for interpretation of forensic toxicological results.
AB  - Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many
      toxicologically important drugs. The gene encoding for this enzyme displays a
      polymorphic distribution in all populations examined. We report a study on 46
      cases, where analyses of the CYP2D6 gene were conducted on postmortem femoral
      blood in order to investigate the occurrence of poor metabolizers (PM). A
      polymerase chain reaction (PCR) method, designed and routinely used for
      therapeutic drug monitoring, was employed, only slightly modified. Samples from
      22 cases, where the parent drug to metabolite ratio was unexpectedly high were
      analyzed as well as samples from 24 control cases. Genotyping could be carried
      out in all but one case. Previous freezing or addition of potassium fluoride as
      preservative did not prevent analysis. Only one PM (from the control group) was
      discovered, implying an occurrence of only 2.2% as compared to the reported
      frequency of approx. 7% in Sweden. Among the extensive metabolizers (EM),
      however, a number of individuals with mutated genes were identified. Although it
      seems reasonable to suspect a PM genotype in cases with a high concentration of a
      drug metabolized by CYP2D6, but without suspicion of acute overdose, our study
      does not support the opinion that this interpretation pitfall is particularly
      common. This study rather indicates that drug interactions in EMs constitute a
      more frequent and important problem.

PMID- 10069021
TI  - Strontium90 for determination of time since death.
AB  - Strontium90 (Sr90) is an artificial nuclear fission product of the atmospheric a
      bomb testing between 1945 and 1979. It was spread throughout the atmosphere in
      the following years. Sr90 is an analogue to calcium and therefore enriched in
      human bones. Several studies especially in the 1960s and 1970s were undertaken to
      investigate the Sr90 burden and the resulting incorporated radiation in humans,
      but present studies are missing. In this study nine bone samples, three from
      1931/32 and six from 1989 to 1994 were examined by measuring the Sr90 radiation.
      The samples from 1931/32 did not show any Sr90 activity. All the samples from
      1989 and later showed a Sr90 activity, but the intensity was very variable.
      Subsequent investigations should be done to determine the cut-off year for
      measurable Sr90 activity. Furthermore the determination of a specific time since
      death depending on Sr90 activity should be possible, due to the ranging Sr90
      pollution between 1950 and 1980 and different uptake in adolescents and adults.

PMID- 10069022
TI  - Bacteria in lung tissue from an autopsy population of alcoholics.
AB  - The retrieval of bacteria from the lungs postmortem was examined in a population
      of alcoholics who had a medico-legal autopsy performed. The results were compared
      with non-alcoholic controls. Pneumococci were found more frequently in
      alcoholics, but in general there were no major differences. Proteus mirabilis was
      detected in three out of five alcoholics with unascertainable cause of death. It
      is speculated whether this species may cause septicaemia in some alcoholics due
      to abnormal splanchnicus circulation.

PMID- 10069023
TI  - Pellet embolization to the right atrium following double shotgun injury.
AB  - A 28-year-old man sustained two shotgun injuries of the left inguinal region from
      a distance of about 1.5 m by simultaneous discharge of both shells from a sawn
      off double-barrelled 16-bore shotgun (diameter of the lead pellets, 4 mm). The
      first X-ray examination carried out soon after hospital admission showed a single
      embolized pellet near the right margin of the cardiac silhouette. Eight months
      later, the man committed suicide by drug intoxication. At autopsy, the embolized
      pellet was found embedded between the pectinate muscles of the right atrium. On
      the basis of the reported case and with reference to the pertinent literature,
      the paper points out the medico-legal aspects of venous bullet/pellet embolism
      and the risk of lead poisoning after shotgun injury.

PMID- 10069024
TI  - Detection of "uncommon" tranquillizers-sedatives during screening toxicological
      analysis.

PMID- 10069025
TI  - Identifying stimuli of different perceptual categories in mixed blocks of trials:
      evidence for cost in switching between computational processes.
AB  - Responding to stimuli of different perceptual categories is usually faster when
      the categories are presented isolated from each other, in pure blocks, than when
      they are presented intermixed, in mixed blocks. According to criterion models,
      these perceptual mixing costs result from the use of a less conservative response
      criterion in pure than in mixed blocks. According to alternate processing models,
      mixing costs result from time-consuming switching in mixed blocks between
      different computational processes called on by the different perceptual
      categories. In 5 experiments, participants had to identify number stimuli of
      different categories. The results showed clear mixing costs whenever these
      categories differed in their assumed computational processing requirements but
      not when they differed on features that seemed trivial from a computational
      viewpoint. The results favor the alternate processing conception.

PMID- 10069026
TI  - Negative identity priming is contingent on stimulus repetition.
AB  - Five experiments demonstrate that negative identity priming is contingent on
      stimulus repetition. In ignored repetition conditions, priming was initially
      positive and became negative as the number of repetitions increased. Moreover, it
      was repetition as a target, not as a distractor, that was critical for negative
      priming. The effects of repetition were general: They were found with both naming
      and same-different paradigms, verbal and pictorial material, familiar and
      unfamiliar stimuli, and vocal and manual responses. Findings support an
      activation-based model of negative priming (G. B. Malley & D. L. Strayer, 1995)
      and are problematic for the episodic retrieval model of negative priming (W. T.
      Neill & L. A. Valdes, 1992). Finally, the experiments did not replicate B.
      DeSchepper and A. Treisman's (1996) reported negative priming with nonrepeated
      novel shapes.

PMID- 10069027
TI  - Attention accesses multiple reference frames: evidence from visual neglect.
AB  - Research with normal participants has demonstrated that mechanisms of selective
      attention can simultaneously gain access to internal representations of spatial
      information defined with respect to both location- and object-based frames of
      reference. The present study demonstrates that patients with unilateral spatial
      neglect following a right-hemisphere lesion are poorer at detecting information
      on the contralateral left side in both location- and object-based spatial
      coordinates simultaneously. Moreover, the extent of the neglect is modulated by
      the probability of a target's appearing in either reference frame; as the
      probability of sampling a target in a particular frame of reference increases, so
      does the severity of neglect in the frame. These findings suggest that attention
      can be flexibly and strategically assigned to a reference frame depending on the
      contingencies of the task.

PMID- 10069028
TI  - Perceptual independence of size and weight by dynamic touch.
AB  - Historically, the existence of a size-weight illusion has led to the conclusion
      that perceptions of size and weight are not independent. A dependence of
      perceived heaviness on physical volume (perceptual separability), however, is
      different from a dependence on perceived volume (perceptual independence). Three
      experiments were conducted to evaluate perceptual independence. The relations
      between perceived size and weight and physical size and mass were evaluated in
      Experiment 1. Perceived weight, length, and width were structured only by the
      corresponding physical variables, whereas variations in volume were not separable
      from variations in mass. F. G. Ashby and J. T. Townsend's (1986) test for
      perceptual independence was applied in Experiment 2. Perceived weight was
      independent of perceived length and volume. Experiment 3 used a magnitude
      estimation paradigm to investigate the extent to which information-perception
      relations could be related to the observed patterns of separability and
      independence.

PMID- 10069029
TI  - Perceiving affordances for another person's actions.
AB  - The perception of affordances for the actions of other people (actors) was
      examined. Observers judged the maximum and preferred sitting heights of tall and
      short actors. Judgments were scaled in centimeters, as a proportion of the
      observer's leg length, and as a proportion of each actor's leg length. In
      Experiment 1 observers viewed live actors standing next to a chair. When
      judgments were scaled by actor leg length, they reflected the actual ordinal
      relation between the capabilities of the actors. The perception of affordances
      from kinematic displays was then evaluated. Observers differentiated tall and
      short actors, but only when the displays contained direct information about
      relations between the actors and the chair. It is concluded that observers can
      perceive affordances for the actions of actors and that kinematic displays can be
      enough to support such percepts if they preserve actor-environment relations that
      define affordances.

PMID- 10069030
TI  - Visual word recognition in bilinguals: evidence from masked phonological priming.
AB  - Bilingual written language representation was investigated with the masked
      phonological priming paradigm. Pseudohomophonic and control primes of French
      target words were used to show that Dutch-French bilinguals exhibit the same
      pattern of phonological and orthographic priming as native French speakers, which
      suggests that the same processes underlie first-and second-language processing.
      It was also found that for bilinguals, but not monolinguals, it is possible to
      prime a target word of the second language with a homophonic stimulus (either
      word or nonword) of the first language. This interlingual phonological priming
      effect was of the same size as the intralingual priming effect. Implications for
      theories of bilingual written language representation and for the interpretation
      of the masked phonological priming paradigm are discussed.

PMID- 10069031
TI  - Processing lexically embedded spoken words.
AB  - A large number of multisyllabic words contain syllables that are themselves
      words. Previous research using cross-modal priming and word-spotting tasks
      suggests that embedded words may be activated when the carrier word is heard. To
      determine the effects of an embedded word on processing of the larger word,
      processing times for matched pairs of bisyllabic words were examined to contrast
      the effects of the presence or absence of embedded words in both 1st- and 2nd
      syllable positions. Results from auditory lexical decision and single-word
      shadowing demonstrate that the presence of an embedded word in the 1st-syllable
      position speeds processing times for the carrier word. The presence of an
      embedded word in the 2nd syllable has no demonstrable effect.

PMID- 10069032
TI  - Interactions between color and word processing in a flanker task.
AB  - To examine interactions between color and word attributes, participants
      responded, either manually or vocally, to a central target (color patch or word)
      flanked by a Stroop stimulus. Color and word attributes of the flanker affected
      both vocal and manual responding to color patches. Color and word flankers also
      affected manual responding to word targets, but only word flanker affected vocal
      responding to word targets. These results are not consistent with models (e.g.,
      translational models) of Stroop tasks, which posit that interactions between
      colors and words occur only when vocal responding is required.

PMID- 10069033
TI  - Inhibition of return in discrimination tasks.
AB  - Although inhibition of return is known to affect a wide range of detection tasks,
      it has not been found consistently in discrimination tasks. To examine this
      issue, 5 experiments were conducted in which participants discriminated between a
      visual target and a distractor. The responses were not inhibited if, before the
      onset of stimuli, attention had been overtly oriented (i.e., an eye movement was
      made) to the future target location and the stimulus at that location was the
      same symbol as the upcoming target. However, if attention was covertly oriented
      (i.e., no eye movement was made) to the future location of the target, or if the
      stimulus at the earlier attended location was a symbol different from the target,
      responses to the target were inhibited. Overall, the findings provide insights
      into the relation between movements of attention and discrimination judgments and
      support the notion that inhibition of return is an attentional phenomenon.

PMID- 10069034
TI  - Speed, size, and edge-rate information for the detection of collision events.
AB  - In the present study an alternative analysis to tau was considered that was based
      on perceived speed and size and that assumed constant deceleration for the
      detection of collision events. Observers were presented with displays simulating
      a 3-D environment with obstacles in the path of observer motion. During the
      trial, observer motion decelerated at a constant rate and was followed by a
      blackout prior to the end of the display. Observers had to detect which trials
      resulted in a collision. The results indicate that collision detection varied as
      a function of the size of the obstacles, observer speed, and edge rate--findings
      not predicted by an analysis of tau. The results suggest that observers use an
      analysis based on speed and size information. A model that assumes constant
      deceleration is proposed for braking control.

PMID- 10069035
TI  - The impact of visual exploration of judgments of whether a gap is crossable.
AB  - When observers look down into a gap in the ground plane, their judgments of the
      widest gap they can step across (gapmax) decrease as gap depth increases (Y.
      Jiang & L. S. Mark, 1994). This study investigated the possibility that Jiang and
      Mark's viewing conditions did not afford observers a sufficient opportunity to
      perform exploratory movements needed to detect information about gap width.
      Experiment 1 showed that the gap depth by gaze interaction disappeared only when
      restrictions were not imposed on observers' exploratory activities (eye, head,
      and body movements). Experiment 2 showed that observers tended to see the
      vertical surface as slanted away from them, which made the bottom of the surface
      appear farther away from them than the top. Only when observers were able to view
      the gap binocularly under conditions that did not restrict exploratory activity
      did their slant perception improve and their gapmax judgments no longer covary
      with gap depth. The data indicate that the exploratory movements of prospective
      actors are essential for the pickup of information about their action
      capabilities.

PMID- 10069036
TI  - Temporal control of feeding behaviour and its association with gastrointestinal
      function.
AB  - This paper summarises knowledge about temporal control of ad libitum feeding in
      poultry, from minute to minute, hour to hour and day to day, and about how it
      relates to aspects of gastrointestinal function. Evidence is presented of only
      loose control over initiation and termination of spontaneous meals, and it is
      proposed that degrees of hunger and satiety determine probabilities of feeding
      starting and stopping. Voluntary regulation of food intake can be considered in
      terms of adjustments in mean meal size, meal frequency or both. Short-term
      variation is associated more with meal frequency and longer-term changes more
      with meal size. Short-term adjustments appear to depend more on alimentary
      control and longer-term adjustments more on metabolic control (not considered
      here). Long-term changes affecting meal size are associated with changes in
      capacity of parts of the alimentary tract. Food can accumulate in the crop and
      gizzard, and meal initiation and termination are associated with varying degrees
      of emptying and filling of these diverticula during most of the day. Later in the
      day there is usually a conditioned change to cumulative filling of the crop (and
      gizzard) with food that is digested overnight. Possible roles of osmo
      /chemoreceptors and gut peptides are discussed.

PMID- 10069037
TI  - Significant role of the nitrogen recycling system through the ceca occurs in
      protein-depleted chickens.
AB  - This study focuses on the role of the ceca in nitrogen nutrition in chickens
      (Gallus domesticus). Urea is a very good nitrogen tracer for these studies.
      Little urea is synthesized by chickens due to the absence of carbamyl phosphate
      synthetase, an essential enzyme initiating the urea cycle. Urea is utilized by
      chickens when crystalline amino acid diets low in nonessential nitrogen or diets
      containing low concentrations of intact protein are fed, and most ureolytic
      activity is found in the ceca. Dietary urea was absorbed intact from the upper
      intestine of the chicken. The absorbed urea was excreted into ureteral urine that
      refluxed from the cloaca into the colon and ceca where urea was degraded to
      ammonia. Presumably the ammonia was incorporated into amino acids by cecal
      microorganisms and some urea, amino acids and proteins were absorbed from the
      ceca. These were utilized by the chickens. A beneficial role of ceca in the
      nitrogen metabolism in the chicken is, therefore, conservation of urinary
      nitrogen in protein-depleted chickens.

PMID- 10069038
TI  - Identification of interstitial cells of Cajal in the digestive tract of turkeys
      (Meleagris gallopavo).
AB  - Interstitial cells of Cajal (ICCs) were identified in the digestive tract of
      turkeys by electron microscopy. ICCs have been implicated as sources of
      pacemaking slow wave potentials that initiate peristalsis in the stomach and
      intestines in mammals. The gastroduodenal contraction cycle in turkeys, however,
      is uniquely coordinated by a neurogenic pacemaker in the isthmus area between the
      glandular stomach and the gizzard, and this controls the coordinated phasic
      contractions of the muscles of the gizzard, duodenum and glandular stomach. Thus,
      it becomes important to look for the presence and distribution of ICCs in the
      avian digestive tract, especially in the gizzard and duodenum. This investigation
      has identified that cells are present which contain the typical characteristics
      of ICCs including: numerous mitochondria, caveolae, thin processes, basement
      membrane, filaments, rough ER, Golgi, and occasional gap junctions. They were
      mostly located in the region of the myenteric plexus between the longitudinal and
      circular muscle layers and occasionally within the longitudinal muscle layer.
      They were frequently near nerve axon bundles and were usually surrounded by
      collagen, elastin fibers, and occasional fibroblasts or blood vessels. ICCs were
      easily found in the ileum, but were also present in the duodenum, cecum, and
      rectum. None were found in the serosal region of the thick muscle of the gizzard.
      The presence of ICCs in the turkey duodenum, which like the gizzard is under
      neurogenic control, suggests that ICCs may play a role(s) in addition to
      initiating peristalsis.

PMID- 10069039
TI  - Release and endogenous actions of the gastrin/cholecystokinin (CCK) family in the
      chicken.
AB  - The regulation of cholecystokinin (CCK) and gastrin release in the chicken and
      their endogenous actions are summarized. Both dietary protein and amino acids
      stimulated CCK releases. Among dietary fat sources, medium-chain triacylglycerol
      (MCT) was a potent stimulator of CCK release compared with long-chain
      triacylglycerol (LCT). However, it is difficult to explain that endogenous CCK
      released by those stimulators has an important role in the avian gastrointestinal
      physiology. Luminal acids may be an important regulator in pancreatic enzyme and
      fluid secretion. Gastrin (a regulator of luminal acid secretion) release was
      stimulated by food components, strongly by MCT, but not by LCT, and weakly by
      some amino acids, and was inhibited by luminal acids. Luminal acids controlled
      food passage from the crop. In conclusion, gastrointestinal physiology may be
      directly regulated by luminal acid rather than by the gastrin/CCK family in the
      chicken.

PMID- 10069040
TI  - Neurotensin modulates the composition of pancreatic exocrine secretions in
      chickens.
AB  - The effects of neurotensin on pancreatic exocrine secretion were examined in
      fasted, conscious White Leghorn hens. A cannula was surgically implanted in the
      central duct serving the ventral lobe of the pancreas in order to collect pure
      pancreatic juice. Following recovery, neurotensin was infused intravenously at
      3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were
      recorded and total pancreatic protein concentration, amylase, lipase, trypsin,
      and chymotrypsin activity were measured every 30 min for 2 hr and compared to
      secretions following the infusion of 0.9% saline. Our results demonstrated that
      neurotensin did not affect the pH nor the pancreatic juice protein concentration,
      but did increase secretion rate following neurotensin infusion at 3.6
      pmol/kg*min. Amylase activity was significantly depressed during neurotensin
      infusions, while lipase (both pancreatic and carboxylester lipase) activity was
      significantly elevated. The ratio of amylase to lipase activity was especially
      depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory
      activity prevented a balanced statistical analysis of chymotrypsin activity, but
      from a pooled analysis, neurotensin had no effect on protease activity in the
      pancreatic juice. These results support our current research indicating that
      neurotensin may be a hormonal regulator of postprandial lipid digestion in
      chickens.

PMID- 10069041
TI  - Effect of galanin on isolated strips of smooth muscle from the gastrointestinal
      tract of chickens.
AB  - The contractile effects of galanin on isolated longitudinal smooth muscle strips
      of pre-crop esophagus, proventriculus, duodenum, colon, and cecum of chickens
      were investigated. Application of galanin (5.0-100.0 nM) evoked strong
      contractions from the colon and cecum (hindgut), but evoked minimal responses
      from the pre-crop esophagus, proventriculus, and duodenum (foregut). Previous
      studies have demonstrated that the central administration of galanin stimulates
      food consumption in rats. Since galanin-like immunoreactivity is present in the
      chicken brain, we speculate that the central release of galanin may increase food
      intake and possibly be involved in a hypothalamic-colonic reflex modulating
      hindgut motility and generating a defecation. Thus, the results of this study
      demonstrate the presence of galanin receptors in the chicken gut and suggest a
      possible link with their functional presence in the hindgut to the chicken
      central nervous system.

PMID- 10069042
TI  - Effect of fasting on small intestinal antiperistalsis in the Nicholas turkey
      (Meleagris gallopavo).
AB  - Small intestinal refluxes (SIRs) were monitored in the gastrointestinal tract of
      Nicholas turkeys via implanted strain gage transducers and radiographic
      observations. It was determined that reflux of ingesta from the small intestine
      into the gizzard was a result of a single antiperistaltic contraction.
      Radiographic observation indicated that the antiperistaltic contraction
      originated in the ileum 88% of the time and the duodenum 12% of the time. Each
      antiperistaltic contraction was preceded by a single peristaltic contraction. No
      gastric contractions occurred during SIRs. Fasting for 12 to 24 hr significantly
      increased the frequency of occurrence of SIRs in the Nicholas turkey (P < 0.0001)
      but had no significant effect on the velocity of the peristaltic and
      antiperistaltic contractions or on recovery time to pre-SIR gastric contractile
      frequency. The pooled mean velocity of peristaltic contractions was determined to
      be 10.55 +/- 3.68 cm/sec, and that of antiperistaltic contractions was determined
      to be 12.12 +/- 3.69 cm/sec. The pooled mean recovery time to pre-SIR gastric
      contraction frequency was 28.31 +/- 8.25 sec. It has been suggested that the SIR
      may be a mechanism of maximizing nutrient utilization by the turkey.

PMID- 10069043
TI  - Mechanisms of excreta formation and elimination in turkeys and ostriches.
AB  - Undigested feed and precipitated uric acid are excreted together in domestic
      turkeys, whereas in ostriches, liquid urine then discrete fecal boli are excreted
      in rapid succession. Gross anatomy and physiology of the cloacal structures of
      these two species also differ, providing an explanation for the differences in
      their waste products.

PMID- 10069044
TI  - Integration of renal and gastrointestinal function.
AB  - In birds, the kidney does not independently regulate the composition of the
      extracellular fluid, as is the case for mammals. The urine of birds enters the
      cloaca and is moved by a reverse peristaltic action into the colon. In the colon,
      the urine comes in contact with an epithelium that modifies its composition. If
      the osmotic potential of the urine is significantly higher than that of the
      plasma, the urine will not be refluxed into the colon. The composition of the
      ureteral urine is sensed in the cloaca which in turn modulates the refluxing
      activity. It appears to be the large contraction waves of the colon that are
      modified by changes in the composition of the urine, although radiographic
      evidence indicates that the small contraction waves of the colon do the actual
      refluxing. It is necessary for the urine to be moved into the colon. This may be
      driven by the need to recover some, if not all, of the protein in the urine. This
      protein maintains uric acid in a colloidal suspension that prevents the formation
      of uric acid crystals which would block the renal tubules. Thus, the kidneys and
      lower gastrointestinal tract must function in concert in the regulation of the
      composition of the extracellular fluid.

PMID- 10069045
TI  - Sites of reaction of pilocarpine.
AB  - Analysis of the sites of reaction of a biologically important compound,
      pilocarpine, a molecule with imidazole and butyrolactone rings connected by a
      methylene bridge, has been accomplished in a quadrupole ion trap with the aim of
      characterizing its structure/reactivity relationships. Ion-molecule reactions of
      pilocarpine with chemical ionizing agents, dimethyl ether (DME), 2
      methoxyethanol, and trimethyl borate (TMB), along with collision-activated
      dissociation elucidated the reaction sites of pilocarpine and made possible the
      comparison of structural features that affect sites of reaction. Based on MS/MS
      experiments, methylation occurs on the imidazole ring upon reactions with
      CH3OCH2+ or (CH3OCH2CH2OH)H+ ions but methylation occurs on the lactone ring for
      reactions with (CH3O)2B+ ions. Bracketing experiments with two model compounds,
      alpha-methyl-gamma-butyrolactone and N-methyl imidazole, show the imidazole ring
      to have a greater gas-phase basicity and methyl cation affinity than the lactone
      ring. The contrast of methylation by TMB ions on the lactone ring is explained by
      initial addition of the dimethoxyborinium ion, (CH3O)2B+, on the imidazole ring
      with subsequent collisional activation promoting an intramolecular transfer of a
      methyl group to the lactone ring with concurrent loss of CH3OBO. Semiempirical
      molecular orbital calculations are undertaken to further address the favored
      reaction sites.

PMID- 10069046
TI  - Do charge-remote fragmentations occur under matrix-assisted laser desorption
      ionization post-source decompositions and matrix-assisted laser desorption
      ionization collisionally activated decompositions?
AB  - The precursor ions of tetraphenylporphyrins that are substituted with fatty acids
      can be introduced into the gas phase by matrix-assisted laser desorption
      ionization (MALDI) and undergo post-source and collisionally activated
      decompositions (CAD) in a time-of-flight mass spectrometer. The goal of the
      research is to obtain a better understanding of post-source decompositions (PSD);
      specifically, we asked the question of whether ions undergoing PSD have
      sufficient energy to give charge-remote fragmentations along an alkyl chain. We
      chose the porphyrin macrocycle because we expected it to act as an inert
      "support," allowing the molecule to be desorbed by MALDI and to be amenable to
      charge-remote fragmentation. MALDI-PSD and MALDI-CAD spectra are similar to high
      energy CAD spectra and considerably more informative than low-energy CAD spectra,
      showing that charge-remote fragmentations of the fatty acid moieties do occur
      upon MALDI-PSD and MALDI-CAD.

PMID- 10069047
TI  - Determining anomericity of the glycosidic bond in Zn(II)-diethylenetriamine
      disaccharide complexes using MSn in a quadrupole ion trap.
AB  - Zinc-diethylenetriamine (Zn-dien) N-glycoside complexes of four 1,4 and four 1,6
      linked disaccharides are prepared. Each reaction mixture is ionized by
      electrospray and the resulting species [Zn(dien)(disaccharide)-H]+ is allowed to
      undergo collision-induced dissociation in a quadrupole ion trap. An MS3 analysis
      is used to differentiate alpha versus beta anomericity of the glycosidic bond in
      the disaccharide moiety. In addition, the MS2 and MS3 spectra can be used
      together to determine the linkage position of this glycosidic bond.

PMID- 10069048
TI  - Modulation frequency and orientation tuning of second-order texture mechanisms.
AB  - Modulation frequency and orientation tuning of second-order mechanisms underlying
      the detection of modulation in local spatial-frequency information are assessed
      by using an oblique-masking paradigm. Stimuli were Gabor-filtered noise patterns
      in which the local carrier spatial frequency was modulated about an average value
      of 4.7 cycles per degree (cpd) according to sinusoidal function. Thresholds were
      determined for spatial-frequency modulated test patterns (0.2 and 0.8 cpd) with
      fixed vertical carrier and modulation orientations presented alone and in the
      presence of spatiotemporally superimposed masks. Mask modulation frequency (0.1,
      0.2, 0.4, 0.8, or 1.6 cpd), modulation orientation (0 degree, 45 degrees, or 90
      degrees relative to vertical), and carrier orientation (18.5 degrees or 90
      degrees relative to vertical) were manipulated independently while the mask
      modulation amplitude remained fixed at 0.25. Manipulating the modulation
      frequency of the mask revealed some modulation frequency specificity,
      particularly at lower test modulation frequencies. Spatial-frequency modulated
      masks produced threshold elevations regardless of the local carrier orientation.
      However, there was no evidence of threshold elevation when the mask modulation
      orientation was orthogonal to that of the test pattern. These results suggest a
      second-order texture mechanism that is tuned to both modulation frequency and
      modulation orientation but is not selective in terms of the orientation of first
      order inputs.

PMID- 10069049
TI  - Noise-resilient estimation of optical flow by use of overlapped basis functions.
AB  - Conventional techniques for the computation of optical flow from image gradients
      are used to formulate the problem as a nonlinear optimization that comprises a
      gradient constraint term and a field smoothness factor. The results of these
      techniques are often erroneous, highly sensitive to noise and numerical
      precision, determined sparsely, and computationally expensive. We regularize the
      gradient constraint equation by modeling optical flow as a linear combination of
      a set of overlapped basis functions. We develop a theory for estimating model
      parameters robustly and reliably. We prove that the extended-least-squares
      solution proposed here is unbiased and robust to small perturbations in the
      gradient estimates and to mild deviations from the gradient constraint. Our
      solution is obtained with a numerically stable sparse matrix inversion, which
      gives a reliable flow-field estimate over the entire frame. To validate our
      claims, we perform a series of experiments on standard benchmark data sets at a
      range of noise levels. Overall, our algorithm outperforms by a wide margin the
      others considered in the comparison. We demonstrate the applicability of our
      algorithm to image mosaicking and to motion superresolution through experiments
      on noisy compressed sequences. We conclude that our flow-field model offers
      greater accuracy and robustness than conventional optical flow techniques in a
      variety of situations and permits real-time operation.

PMID- 10069050
TI  - The Rose model, revisited.
AB  - In 1946 and 1948, three very important papers by Albert Rose [J. Soc. Motion
      Pict. Eng. 47, 273 (1946); J. Opt. Soc. Am. 38, 196 (1948); L. Marton, ed.
      (Academic, New York, 1948)] were published on the role that photon fluctuations
      have in setting fundamental performance limits for both human vision and
      electronic imaging systems. The papers were important because Rose demonstrated
      that the performance of imaging devices can be evaluated with an absolute scale
      (quantum efficiency). The analysis of human visual signal detection used in these
      papers (developed before the formal theory of signal detectability) was based on
      an approach that has come to be known as the Rose model. In spite of its
      simplicity, the Rose model is a very good approximation of a Bayesian ideal
      observer for the carefully and narrowly defined conditions that Rose considered.
      This simple model can be used effectively for back-of-the-envelope calculations,
      but it needs to be used with care because of its limited range of validity. One
      important conclusion arising from Rose's investigations is that pixel signal-to
      noise ratio is not a good figure of merit for imaging systems or components, even
      though it is still occasionally used as such by some researchers. In the present
      study, (1) aspects of signal detection theory are presented, (2) Rose's model is
      described and discussed, (3) pixel signal-to-noise ratio is discussed, and (4)
      progress on modeling human noise-limited performance is summarized. This study is
      intended to be a tutorial with presentation of the main ideas and provision of
      references to the (dispersed) technical literature.

PMID- 10069051
TI  - Why use noise?
AB  - Measuring the dependence of visual sensitivity on parameters of the visual
      stimulus is a mainstay of vision science. However, it is not widely appreciated
      that visual sensitivity is a product of two factors that are each invariant with
      respect to many properties of the stimulus and task. By estimating these two
      factors, one can isolate visual processes more easily than by using sensitivity
      measures alone. The underlying idea is that noise limits all forms of
      communication, including vision. As an empirical matter, it is often useful to
      measure the human observer's threshold with and without a noise background added
      to the display, to disentangle the observer's ability from the observer's
      intrinsic noise. And when we know how much noise there is, it is often useful to
      calculate ideal performance of the task at hand, as a benchmark for human
      performance. This strips away the intrinsic difficulty of the task to reveal a
      pure measure of human ability. Here we show how to do the factoring of
      sensitivity into efficiency and equivalent noise, and we document the invariances
      of the two factors.

PMID- 10069052
TI  - Effects of aging on calculation efficiency and equivalent noise.
AB  - Contrast sensitivity under photopic conditions declines with age; however, the
      cause of this decline remains unknown. To address this issue, we measured
      detection thresholds for sine wave gratings in noise, under various conditions of
      spatial-frequency uncertainty, and estimated observers' internal noise and
      calculation efficiency. Statistical analyses revealed that efficiencies were
      lower for old (median age at 68 years) than for young (median age at 22 years)
      observers; no significant differences in internal noise were found. A control
      experiment ruled out the possibility that reduced retinal illuminance causes the
      decline in efficiency with age. Our results demonstrate that age-related neural
      changes play a major role in the decline in contrast sensitivity with age.
      Possible contributing mechanisms are considered.

PMID- 10069053
TI  - Role of phase information and eye pursuit in the detection of moving objects in
      noise.
AB  - As part of an ongoing study that uses objective image quality measures to
      optimize medical imaging x-ray fluoroscopy, we investigated two basic features of
      the detection of moving cylinders that mimic arteries, catheters, and guide
      wires. First, we compared detection with and without a phase cue consisting of a
      nearby alternating light and dark square. Depending on object size and velocity,
      phase cuing improved detection from 1% to 15% and gave an average of 6%, an
      effect much smaller than the 38% predicted from a Monte Carlo simulation of the
      ideal observer. Evidently, humans were limited in their ability to incorporate
      knowledge of the phase cue. Second, we evaluated the effect of eye pursuit of a
      fixation point that moved with the target. In general, motion at the highest
      velocity degraded (74%) and enhanced (68%) detection of small and large objects,
      respectively. With eye pursuit, both effects were substantially reduced in a
      manner consistent with a reduced retinal velocity. Our data compared favorably
      with a human observer model that included a spatiotemporal contrast sensitivity
      response and smooth-pursuit eye movements with a gain of 0.8. These mechanisms of
      perception are thought to be present in coronary artery x-ray fluoroscopy
      imaging, where phase information is available from the moving heart and where
      motion markers are available from x-ray opaque markers incorporated in thin
      catheters and guide wires.

PMID- 10069054
TI  - Prediction of human observer performance by numerical observers: an experimental
      study.
AB  - Numerical observers are investigated for predicting the outcome of a free
      response human observer study involving the detection of simulated pulmonary
      nodules in images reconstructed from low-dose computed tomography projection data
      by use of several reconstruction algorithms. A new way of calculating the figure
      of merit of a numerical observer is proposed wherein the detectability of signals
      in a particular image depends on the noise properties associated with that image
      and not the other images in the data set. The resulting variants of numerical
      observers are found to perform better than their traditional counterparts. In
      particular, the imagewise variant of the region-of-interest observer is found to
      predict best the rank ordering of algorithms by human observers for the free
      response task.

PMID- 10069055
TI  - Visual signal detection with two-component noise: low-pass spectrum effects.
AB  - Detection of signals in natural images and scenes is limited by both noise and
      structure. The purpose of this study is to investigate phenomenological issues of
      signal detection in two-component noise. One component had a broadband (white)
      spectrum designed to simulate image noise. The other component was filtered to
      simulate two classes of low-pass background structure spectra: Gaussian-filtered
      noise and power-law noise. Measurements of human and model observer performance
      are reported for several aperiodic signals and both classes of background
      spectra. Human results are compared with two classes of observer models and are
      fitted very well by suboptimal prewhitening matched filter models. The
      nonprewhitening model with an eye filter does not agree with human results when
      background-noise-component power spectrum bandwidths are less than signal energy
      bandwidths.

PMID- 10069056
TI  - Noise and its effects on photoreceptor temporal contrast sensitivity at low light
      levels.
AB  - We studied photoreceptors in the locust (Schistocerca americanus) visual system
      to determine the extent to which quantal noise and intrinsic neural noise limit
      temporal sensitivity. Typical computational models of the temporal contrast
      sensitivity function are deterministic, reflect only filter characteristics, and
      lack explicit noise sources [J. Opt. Soc. Am. 58, 1133 (1968); Vision Res. 32,
      1373 (1992)]. We report here that the temporal contrast sensitivity function, at
      low light levels, is not simply the reflection of a filter function. Our evidence
      suggests that, at low backgrounds, noise, in conjunction with temporal filtering,
      plays a role in shaping the temporal contrast sensitivity function. At a given
      low adaptation level, quantal noise limits sensitivity at low temporal
      frequencies, while intrinsic noise limits sensitivity at relatively higher
      temporal frequencies.

PMID- 10069057
TI  - Noise location and the slope of the psychometric function for simple motion
      stimuli.
AB  - We measured subject performance as a function of luminance for both detection and
      discrimination of increment stimuli; some were static, and some were arranged to
      give two-step apparent motion. Our aim was to examine a prediction for the shape
      of the psychometric function for motion: an accelerating function due to the
      presence of a multiplicative nonlinearity contained in many low-level motion
      models. For the tasks with static stimuli we found psychometric function slopes
      (of log d' versus log luminance plots) between 1.9 and 2.4 in two subjects, as
      previously reported. For the tasks with apparent motion stimuli in the same range
      of detectability, however, the slopes are between 1.2 and 1.7. The lower slopes
      indicate that many low-level motion models are either incorrect or incomplete as
      currently specified, and changes in nonlinearities and noise placement are
      discussed.

PMID- 10069058
TI  - Local versus global contrasts in texture segregation.
AB  - In a texture pair (TP) yielding a vertical or horizontal edge, the local
      (luminance or color) contrast or the local orientation of the individual textels
      is traded off with the global strength of the luminance-, color-, or orientation
      defined TP edge so as to keep the latter at the detection threshold. Local and
      global contrasts are defined along the same (within-domain conditions) or along
      distinct physical dimensions (transdomain conditions). In the latter case local
      luminance or color contrast is traded off against global orientation. In all
      cases TP's are presented for 66.7 or 333.3 ms. Textels differ from the background
      in either luminance or color so that the TP's are respectively equichromatic or
      equiluminant. TP edge strength is modulated by means of swapping variable
      proportions of textels between the two textures in the TP. The observed local-
      global relationships are fitted with a version of the equivalent noise model for
      contrast coding modified to include the presentation time factor. The extension
      of the standard model in the time domain is meant to allow comparison between
      equivalent noise estimates for variable duration stimuli. Model fits of the
      within-domain data yield equivalent noise energy values significantly different
      for color- and luminance-defined TP's but are not applicable for the transdomain
      experiments, which indicates that global orientation processing is independent of
      both local luminance and local color contrast insofar as the latter are above the
      detection threshold. Finally, this study points to the equivalence among the
      local--global, the equivalent noise, and the statistical approaches to texture
      segregation.

PMID- 10069059
TI  - Detection improvement in spatially filtered x-ray fluoroscopy image sequences.
AB  - The effect of spatial noise-reduction filtering on human observer detection of
      stationary cylinders mimicking arteries, catheters, and guide wires in x-ray
      fluoroscopy was investigated in both single image frames and image sequences.
      Ideal edge-preserving spatial filtering was simulated by filtering of the noise
      before addition of the target cylinder. This allowed us to separate the effect of
      edge blurring from those of noise reduction and spatial noise correlation. We
      used three different center-weighted averagers that reduced pixel noise variance
      by factors of 0.75, 0.50, and 0.25. As compared with no filtering, the effect of
      filtering on detection in single images was statistically insignificant. This
      indicated an adverse effect of spatial noise correlation on detection that
      countered the effect of noise reduction. By comparison, spatial filtering
      significantly improved detection in image sequences and yielded potential x-ray
      dose savings of 26-34%. Comparison of results with two observer models suggested
      that human observers have an improved detection efficiency in spatially filtered
      image sequences as compared with white-noise sequences. Pixel noise reduction, a
      measure commonly used to assess filter performance, overestimated the effect of
      filtering on detection and was not a good indicator of image quality. We conclude
      that edge-preserving spatial filtering is more effective in sequences than in
      single images and that such filtering can be used to improve image quality in
      noisy image sequences such as x-ray fluoroscopy.

PMID- 10069060
TI  - Flash masking and facilitation by nearby luminance perturbations.
AB  - Light-adapted foveal luminance increment thresholds were measured for white
      photopic targets of 1.5-arc min diameter and 220-ms duration. We aimed to learn
      about the properties of mechanisms that subserve the detection of these targets.
      To study this subject we developed a noise probe technique that inserts noise
      close to the site of the stimulus. Threshold is more than doubled when zero-mean
      luminance noise is placed at a pair of flanking spots in the horizontal meridian
      centered on the test spot and 1.5 arc min distant. The detection mechanisms thus
      has a broad field, since noise effects persist at 5-arc min separation. The
      masking effect increases when the noise is in antiphase at the two flanking
      spots. Neither even- nor odd-symmetric mechanisms are able to explain these
      findings, regardless of whether linear or nonlinear processing is employed. The
      target detection may be mediated in part by a motion-sensitive mechanism.

PMID- 10069061
TI  - Detection in fixed and random noise in foveal and parafoveal vision explained by
      template learning.
AB  - Foveal and parafoveal contrast detection thresholds for Gabor and checkerboard
      targets were measured in white noise by means of a two-interval forced-choice
      paradigm. Two white-noise conditions were used: fixed and twin. In the fixed
      noise condition a single noise sample was presented in both intervals of all the
      trials. In the twin noise condition the same noise sample was used in the two
      intervals of a trial, but a new sample was generated for each trial. Fixed noise
      conditions usually resulted in lower thresholds than twin noise. Template
      learning models are presented that attribute this advantage of fixed over twin
      noise either to fixed memory templates' reducing uncertainty by incorporation of
      the noise or to the introduction, by the learning process itself, of more
      variability in the twin noise condition. Quantitative predictions of the template
      learning process show that it contributes to the accelerating nonlinear increase
      in performance with signal amplitude at low signal-to-noise ratios.

PMID- 10069062
TI  - Characterizing human perceptual inefficiencies with equivalent internal noise.
AB  - A widely used method for characterizing and comparing inefficiencies in
      perceptual processes is the method of equivalent internal noise--the amount of
      random internal noise necessary to produce the degree of inefficiency exhibited
      by the perceptual system in processing [J. Opt. Soc. Am. 46, 634 (1956)]. One
      normally estimates the amount of equivalent internal noise by systematically
      increasing the amount of external noise added to the signal stimulus and
      observing how threshold--signal stimulus energy required for an observer to
      maintain a given performance level--depends on the amount of external noise. In a
      variety of perceptual tasks, a simple noisy linear amplifier model [D. Pelli,
      Ph.D. dissertation (University of Cambridge, Cambridge, UK 1981)] has been
      utilized to estimate the equivalent internal noise Ninternal by fitting of the
      relation between threshold contrast c tau and external noise N(ext) at a single
      (d') performance level: c tau 2 =(d'/beta)2(N(ext)2 + Ninternal2). This model
      makes a strong prediction: Independent of observer and external noise contrast,
      the ratio between two thresholds at each external noise level is equal to the
      ratio of the two corresponding d' values. To our knowledge, this potential test
      for the internal consistency of the model had never been examined previously. In
      this study we estimated threshold ratios between multiple performance levels at
      various external noise contrasts in two different experiments: Gabor orientation
      identification, and Gabor detection. We found that, in both identification and
      detection, the observed threshold ratios between different performance levels
      departed substantially from the d' ratio predicted by the simple noisy linear
      amplifier model. An elaborated perceptual template model [Vision Res. 38, 1183
      (1998)] with nonlinear transducer functions and multiplicative noise in addition
      to the additive noise in the simple linear amplifier model leads to a
      substantially better description of the data and suggests a reinterpretation of
      earlier results that relied on the simple noisy linear amplifier model. The
      relationship of our model and method to other recent parallel and independent
      developments [J. Opt. Soc. Am. A 14, 2406 (1997)] is discussed.

PMID- 10069063
TI  - Target genes and regulatory domains of the GAMYB transcriptional activator in
      cereal aleurone.
AB  - GAMYB is an MYB transcription factor which is expressed in cereal aleurone cells
      in response to gibberellin (GA). HvGAMYB binds to the TAACAAA box of a high-pl
      alpha-amylase gene promoter and transcriptionally activates its expression. In
      this study, we examined the role of HvGAMYB in activating expression of other GA
      regulated genes encoding hydrolytic enzymes. In transient expression experiments,
      HvGAMYB transactivated expression of reporter genes fused to a low-pl alpha
      amylase gene promoter, an EII (1-3, 1-4)-beta-glucanase gene promoter and a
      cathepsin B-like protease promoter. HvGAMYB DNA binding specificity was
      determined using a PCR-based random site selection using HvGAMYB fusion protein
      isolated from E. coli. The deduced consensus closely resembled gibberellin
      response elements in alpha-amylase promoters. Functional analysis of HvGAMYB by
      transient expression of C terminal HvGAMYB deletions in barley aleurone cells
      identified two transcriptional activation domains (TADs) which function in
      transcriptional regulation of both high- and low-pl alpha-amylase promoters. The
      same TADs were identified using a heterologous yeast expression system. Together,
      these results indicate that HvGAMYB has two TADs. These domains are C-terminal to
      its DNA-binding domain.

PMID- 10069064
TI  - A 100 kDa polypeptide associates with the V0 membrane sector but not with the
      active oat vacuolar H(+)-ATPase, suggesting a role in assembly.
AB  - The vacuolar H(+)-ATPase (V-ATPase) is responsible for acidifying endomembrane
      compartments in eukaryotic cells. Although a 100 kDa subunit is common to many V
      ATPases, it is not detected in a purified and active pump from oat (Ward J.M. and
      Sze H. (1992) Plant Physiol. 99, 925-931). A 100 kDa subunit of the yeast V
      ATPase is encoded by VPH1. Immunostaining revealed a Vph1p-related polypeptide in
      oat membranes, thus the role of this polypeptide was investigated. Membrane
      proteins were detergent-solubilized and size-fractionated, and V-ATPase subunits
      were identified by immunostaining. A 100 kDa polypeptide was not associated with
      the fully assembled ATPase; however, it was part of an approximately 250 kDa V0
      complex including subunits of 36 and 16 kDa. Immunostaining with an affinity
      purified antibody against the oat 100 kDa protein confirmed that the polypeptide
      was part of a 250 kDa complex and that it had not degraded in the approximately
      670 kDa holoenzyme. Co-immunoprecipitation with a monoclonal antibody against A
      subunit indicated that peripheral subunits exist as assembled V1 subcomplexes in
      the cytosol. The free V1 subcomplex became attached to the detergent-solubilized
      V0 sector after mixing, as subunits of both sectors were co-precipitated by an
      antibody against subunit A. The absence of this polypeptide from the active
      enzyme suggests that, unlike the yeast Vph1p, the 100 kDa polypeptide in oat is
      not required for activity. Its association with the free Vo subcomplex would
      support a role of this protein in V-ATPase assembly and perhaps in sorting.

PMID- 10069065
TI  - Phylogenetic transfer of organelle genes to the nucleus can lead to new
      mechanisms of protein integration into membranes.
AB  - Subunits CFo-I and CFo-II of ATP synthase in chloroplast thylakoid membranes are
      two structurally and functionally closely related proteins of bitopic membrane
      topology which evolved from a common ancestral gene. In higher plants, CFo-I
      still originates in plastid chromosomes (gene: atpF), while the gene for CFo-II
      (atpG) was phylogenetically transferred to the nucleus. This gene transfer was
      accompanied by the reorganization of the topogenic signals and the mechanism of
      membrane insertion. CFo-I is capable of integrating correctly as the mature
      protein into the thylakoid membrane, whereas membrane insertion of CFo-II
      strictly depends on a hydrophobic targeting signal in the transit peptide. This
      requirement is caused by three negatively charged residues at the N-terminus of
      mature CFo-II which are lacking from CFo-I and which have apparently been added
      to the protein only after gene transfer has occurred. Accordingly, the CFo-II
      transit peptide is structurally and functionally equivalent to typical bipartite
      transit peptides, capable of also translocating hydrophilic lumenal proteins
      across the thylakoid membrane. In this case, transport takes place by the Sec
      dependent pathway, despite the fact that membrane integration of CFo-II is a Sec
      independent, and presumably spontaneous, process.

PMID- 10069066
TI  - Plants expressing the Pto disease resistance gene confer resistance to
      recombinant PVX containing the avirulence gene AvrPto.
AB  - Elicitation of hypersensitive cell death and induction of plant disease
      resistance by Pseudomonas syringae pv. tomato (Pst) is dependent on activity of
      the Pst Hrp secretion system and the gene-for-gene interaction between the tomato
      resistance gene Pto and the bacterial avirulence gene avrPto. AvrPto was
      expressed transiently in resistant or susceptible plant lines via a potato virus
      X (PVX) vector. We found that while PVX is normally virulent on tomato, a PVX
      derivative expressing avrPto was only capable of infecting plants lacking a
      functional Pto resistance pathway. Mutations in either the Pto or Prf genes
      allowed systemic spread of the recombinant virus. These results indicate that
      recognition of AvrPto by Pto in resistant plant lines triggers a plant defense
      response that can confer resistance to a viral as well as a bacterial pathogen.

PMID- 10069067
TI  - Organ identity genes and modified patterns of flower development in Gerbera
      hybrida (Asteraceae)
AB  - We have used Gerbera hybrida (the cultivated ornamental, gerera) to investigate
      the molecular basis of flower development in Asteraceae, a family of flowering
      plants that have heteromorphic flowers and specialized floral organs. Flowers of
      the same genotype may differ in a number of parameters, including sex expression,
      symmetry, sympetaly and pigmentation. In order to study the role of organ
      identity determination in these phenomena we isolated and functionally analysed
      six MADS box genes from gerbera; these were shown by phylogenetic analysis to be
      orthologous to well characterized regulatory genes described from Arabidopsis and
      Antirrhinum. Expression analysis suggests that the two gerbera agamous
      orthologues, the globosa orthologue and one of the deficiens orthologues may have
      functional equivalency to their counterparts, participating in the C and B
      functions, respectively. However, the function of a second deficiens orthologue
      appears unrelated to the B function, and that of a squamosa orthologue seems
      distinct from squamosa as well as from the A function. The induction patterns of
      gerbera MADS box genes conform spatiotemporally to the multi-flowered, head-like
      inflorescence typical of Asteraceae. Furthermore, gerbera plants transgenic for
      the newly isolated MADS box genes shed light onto the mechanistic basis for some
      floral characteristics that are typical for Asteraceae. We can conclude,
      therefore, that the pappus bristles are sepals highly modified for seed
      dispersal, and that organ abortion in the female marginal flowers is dependent
      upon organ identity and not organ position when position is homeotically altered.

PMID- 10069068
TI  - Circadian dysfunction causes aberrant hypocotyl elongation patterns in
      Arabidopsis.
AB  - Many endogenous and environmental signals control seedling growth, including
      several phototransduction pathways. We demonstrate that the circadian clock
      controls the elongation of the Arabidopsis hypocotyl immediately upon
      germination. The pattern of hypocotyl elongation in constant light includes a
      daily growth arrest spanning subjective dawn and an interval of rapid growth at
      subjective dusk. Maximal hypocotyl growth coincides with the phase during which
      the cotyledons are raised, in the previously described rhythm of cotyledon
      movement. The rhythm of hypocotyl elongation was entrained by light-dark cycles
      applied to the imbibed seed and its period was shortened in the toc1-1 mutant,
      indicating that it is controlled by a similar circadian system to other rhythmic
      markers. The daily groth arrest is abolished by the early flowering 3 (elf3)
      mutation, suggesting that this defect may cause its long-hypocotyl phenotype.
      Mutations that affect the circadian system can therefore cause gross
      morphological phenotypes, not because the wild-type gene functions
      pleiotropically in several signalling pathways, but rather because the circadian
      clock exerts wide-spread control over plant physiology.

PMID- 10069069
TI  - Comparative analysis of S haplotypes with very similar SLG alleles in Brassica
      rapa and Brassica oleracea.
AB  - Self-incompatibility in Brassica is controlled by a single multi-allelic locus
      (the S locus) which harbors at least two highly polymorphic genes, SLG and SRK.
      SRK is a putative transmembrane receptor kinase and its amino acid sequence of
      the extracellular domain of SRK (the S domain) exhibits high homology to that of
      SLG. The amino acid sequences of the SLGs of S8 and S46 haplotypes of B. rapa are
      very similar and those of S23 and S29 haplotypes of B. oleracea were also found
      to be almost identical. In both cases, SLG and the S domain of SRK of the same
      haplotype were less similar. This seems to contradict the idea that SLG and SRK
      of the same haplotype have the same self-recognition specificity. In the
      transmembrane-kinase domain, the SRK alleles of the S8 and S46 haplotypes had
      almost identical nucleotide sequences in spite of their lower homology in the S
      domain. Such a cluster of nucleotide substitutions is probably due to
      recombination or related events, although recombination in the S locus is thought
      to be suppressed. Based on our observations, the recognition mechanism and the
      evolution of self-incompatibility in Brassica are discussed.

PMID- 10069070
TI  - Iron homeostasis alteration in transgenic tobacco overexpressing ferritin.
AB  - Intracellular iron concentration requires tight control and is regulated both at
      the uptake and storage levels. Our knowledge of the role that the iron-storage
      protein ferritins play in plants is still very limited. Overexpression of this
      protein, either in the cytoplasm or the plastids of transgenic tobacco, was
      obtained by placing soybean ferritin cDNA cassettes under the control of the CAMV
      35S promoter. The protein accumulated in 4- and 6-day-old seedlings and in leaves
      of 3-week-old plants but not in dry seeds or in 2-day-old seedlings, which is
      consistent with previous reports describing a post-transcriptional control of
      ferritin amounts during the germination process. Overaccumulated ferritin in
      leaves was correctly assembled as 24-mers. Transformants were more resistant to
      methylviologen toxicity, indicating that the transgenic ferritins were functional
      in vivo. Ferritin overaccumulation in transgenic tobacco leaves leads to an
      illegitimate iron sequestration. As a consequence, these transgenic plants behave
      as iron deficient and activate iron transport systems as revealed by an increase
      in root ferric reductase activity and in leaf iron content.

PMID- 10069071
TI  - Genetic engineering of the multicellular green alga Volvox: a modified and
      multiplied bacterial antibiotic resistance gene as a dominant selectable marker.
AB  - The green alga Volvox represents the simplest multicellular organism: Volvax is
      composed of only two cell types, somatic and reproductive. Volvox, therefore, is
      an attractive model system for studying various aspects of multicellularity. With
      the biolistic nuclear transformation of Volvox carteri, the powerful molecular
      genetic manipulation of this organism has been established, but applications have
      been restricted to an auxotrophic mutant serving as the DNA recipient. Therefore,
      a dominant selectable marker working in all strains and mutants of this organism
      is required. Among several gene constructs tested, the most advantageous results
      were obtained with a chimeric gene composed of the coding sequence of the
      bacterial ble gene, conferring resistance to the antibiotic zeocin, modified with
      insertions of two endogenous introns from the Volvox arylsulfatase gene and fused
      to 5' and 3' untranslated regions from the Volvox beta 2-tubulin gene. In the
      most suitable plasmid used, the gene dosage was increased 16-fold by a technique
      that allows exponential multiplication of a DNA fragment. Co-transformation of
      this plasmid and a non-selectable plasmid allowed the identification of zeocin
      resistant transformants with nuclear integration of both selectable and non
      selectable plasmids. Stable expression of the ble gene and of genes from several
      non-selectable plasmids is demonstrated. The modified ble gene provides the first
      dominant marker for transformation of both wild-type and mutant strains of
      Volvox.

PMID- 10069072
TI  - Construction of two ordered cDNA libraries enriched in genes encoding plasmalemma
      and tonoplast proteins from a high-efficiency expression library.
AB  - We constructed a high-efficiency expression library from Arabidopsis cDNA clones
      by introducing a poly (dC) stretch at the 5' end of the clones. This library
      enables the synthesis of proteins from all the cDNA clones present. We have
      screened the high-efficiency expression library with antibodies raised against
      total proteins from Arabidopsis plasmalemma and tonoplast. With the positive
      clones, we have constructed two cDNA ordered libraries enriched in genes encoding
      plasmalemma (522 clones) and tonoplast proteins (594 clones). Partial sequencing
      of both libraries shows that a high proportion (47%) of the clones encoded
      putative membrane proteins, or membrane-associated proteins. When sequenced, 55%
      of the cDNAs were new EST sequences for Arabidopsis, 26% were similar to genes
      present in other plants or organisms, and 29% were not referenced in any
      databank. Immunoscreening of the two cDNA ordered libraries with antibodies
      raised against proteins from Arabidopsis cells submitted to osmotic stress allows
      the selection of genes over- and under-expressed in stress conditions.

PMID- 10069073
TI  - Transgene-induced gene silencing in plants.

PMID- 10069074
TI  - Direct repeats of T-DNA integrated in tobacco chromosome: characterization of
      junction regions.
AB  - Plant transformation via Agrobacterium frequently results in formation of
      multiple copy T-DNA arrays at one target site of the chromosome. The T-DNA copies
      are arranged in repeats, direct or inverted around one of the T-DNA borders. A Ti
      plasmid-derived transformation vector has been constructed enabling direct
      selection of transformants carrying at least two linked copies of T-DNA in the
      same orientation. The selection is based on expression of a promoterless neomycin
      phosphotransferase gene on one T-DNA copy from a promoter located on the other T
      DNA copy. After co-cultivation of tobacco protoplasts with Agrobacterium, as many
      as 30% of regenerated transformed plants carried directly repeated T-DNA copies.
      The junction regions between two T-DNAs were amplified and 13 amplified fragments
      were cloned and sequenced. The involvement of T-DNA left and right border
      sequences in direct repeat junctions was determined. In some junctions,
      additional filler DNA was detected. The length of filler DNA varied from a few up
      to almost 300 bp. The longer filler DNAs from two clones were found to be T-DNA
      fragments in direct or reverse orientation. We discuss the recently suggested
      models for T-DNA integration and propose that the formation of direct repeats in
      genomes does not necessarily result from ligation of intermediates (i.e. T
      strands), but more likely from the co-integration of several intermediates into
      one target site.

PMID- 10069075
TI  - A history of stress alters drought calcium signalling pathways in Arabidopsis.
AB  - Environmental stresses commonly encountered by plants lead to rapid transient
      elevations in cytosolic free calcium concentration ([Ca2+]cyt) (Bush, 1995;
      Knight et al., 1991). These cellular calcium (Ca2+) signals lead ultimately to
      the increased expression of stress-responsive genes, including those encoding
      proteins of protective function (Knight et al., 1996; Knight et al., 1997). The
      kinetics and magnitude of the Ca2+ signal, or 'calcium signature', differ between
      different stimuli and are thought to contribute to the specificity of the end
      response (Dolmetsch et al., 1997; McAinsh and Hetherington, 1998). We measured
      [Ca2+]cyt changes during treatment with mannitol (to mimic drought stress) in
      whole intact seedlings of Arabidopsis thaliana. The responses of plants which
      were previously exposed to osmotic and oxidative stresses were compared to those
      of control plants. We show here that osmotic stress-induced Ca2+ responses can be
      markedly altered by previous encounters with either osmotic or oxidative stress.
      The nature of the alterations in Ca2+ response depends on the identity and
      severity of the previous stress: oxidative stress pre-treatment reduced the
      mannitol-induced [Ca2+]cyt response whereas osmotic stress pretreatment increased
      the [Ca2+]cyt response. Therefore, our data show that different combinations of
      environmental stress can produce novel Ca2+ signal outputs. These alterations are
      accompanied by corresponding changes in the patterns of osmotic stress-induced
      gene expression and, in the case of osmotic stress pre-treatment, the acquisition
      of stress-tolerance. This suggests that altered Ca2+ responses encode a 'memory'
      of previous stress encounters and thus may perhaps be involved in acclimation to
      environmental stresses.

PMID- 10069076
TI  - Treatment of Vicia faba root tip cells with specific inhibitors to cyclin
      dependent kinases leads to abnormal spindle formation.
AB  - Many events during cell division are triggered by an evolutionary conserved
      regulator, the cyclin-dependent kinase (Cdk). Here we used two novel drugs, the
      purine analogues bohemine and roscovitine, to study the role of Cdks in cell
      cycle progression and microtubule organisation in Vicia faba root tip cells. Both
      drugs inhibited the activity of immunopurified Vicia faba and alfalfa Cdc2
      kinase. The transcript levels of an A- and B-type cyclin, as well as of the cdc2
      genes, declined in treated root tips, while the mRNA level of a D-type cyclin
      gene was not affected. An observed transient arrest at the G1/S and G2/M
      regulatory points indicated that inhibition of the Cdc2-kinase had an effect on
      both transitions. In contrast to the regular bipolar spindle in untreated cell,
      in drug-treated metaphase cells abnormally short and dense kinetochore
      microtubule fibres were observed. These microtubules were randomly arranged in
      the vicinity of the kinetochores and connected the chromosomes. Thus, the
      chromosomes were not aligned on the metaphase plate but were arranged in a
      circle, with kinetochores pointing inwards and chromosome arms pointing outwards.
      gamma-Tubulin, which plays a role in microtubule nucleation, also localised to
      the centre of the monopolar spindle. The observed abnormalities in mitosis, after
      inhibition of Cdc2-kinase by specific drugs, suggest a role for this enzyme in
      regulating some of the steps leading to a bipolar spindle structure.

PMID- 10069077
TI  - Mutational analyses of a type 2 peroxisomal targeting signal that is capable of
      directing oligomeric protein import into tobacco BY-2 glyoxysomes.
AB  - In this study of the type 2 peroxisomal targeting signal (PTS2) pathway, we
      examined the apparent discontinuity and conservation of residues within the PTS2
      nonapeptide and demonstrated that this topogenic signal is capable of directing
      heteromultimeric protein import in plant cells. Based on cumulative data showing
      that at least 26 unique, putative PTS2 nonapeptides occur within 12 diverse
      peroxisomal-destined proteins, the current (-R/K-L/V/I-X5-H/Q-L/A-) as well as
      the original (-R-L-X5-H/Q-L-) PTS2 motif appear to be oversimplified. To assess
      the functionality of residues within the motif, rat liver thiolase (rthio) and
      various chimeric chloramphenicol acetyltransferase (CAT) proteins were expressed
      transiently in suspension-cultured tobacco (Nicotiana tabaccum L.) cv Bright
      Yellow cells (BY-2), and their subcellular location was determined by
      immunofluoresence microscopy. Hemagglutinin (HA)-epitope-tagged-CAT subunits,
      lacking a PTS2 (CAT-HA), were 'piggybacked' into glyoxysomes by PTS2-bearing CAT
      subunits (rthio-CAT), whereas signal-depleted CAT-HA subunits that were modified
      to prevent oligomerization did not import into glyoxysomes. These results
      provided direct evidence that signal-depleted subunits imported into peroxisomes
      were targeted to the organelle as oligomers (heteromers) by a PTS2. Mutational
      analysis of residues within PTS2 nonapeptides revealed that a number of amino
      acid substitutions were capable of maintaining targeting function. Furthermore,
      functionality of residues within the PTS2 nonapeptide did not appear to require a
      context-specific environment conferred by adjacent residues. These results
      collectively suggest that the functional PTS2 is not solely defined as a sequence
      specific motif, i.e. -R/K-X6-H/Q-A/L/F-, but defined also by its structural motif
      that is dependent upon the physiochemical properties of residues within the
      nonapeptide.

PMID- 10069078
TI  - A Ty3/gypsy retrotransposon-like sequence localizes to the centromeric regions of
      cereal chromosomes.
AB  - A 745 bp sequence (pSau3A9) located at the centromeres of several cereal species
      was isolated from a sorghum BAC library by Jiang et al. (1996, Proc. Natl Acad.
      Sci. USA, 93, 14210-14213). We have amplified a partially homologous 809 bp
      sequence from barely genomic DNA by PCR and localized it to the centromeres of
      barley, wheat and rye chromosomes by fluorescent in situ hybridization (FISH).
      Sequence analysis showed this barley homolog of pSau3A9 to have high similarity
      to the integrase region of the polyprotein gene of Ty3/gypsy group
      retrotransposons. Using this integrase sequence as a probe, several clones were
      isolated from a lambda library constructed of genomic barley DNA. One of the
      lambda clones contained coding regions for all five catalytic sites
      characteristic of the retrotransposon polyprotein. Two direct repeats flanking
      the polyprotein gene are homologous to the cereal centromeric sequence described
      by Aragon-Alcaide et al. (1996, Chromosoma, 105, 261-268) and may represent all
      or part of the long-terminal repeats (LTRs). Different plasmid subclones
      containing various regions of the lambda clone were used in FISH to show that the
      entire polyprotein gene and upstream flanking sequences, including the presumed
      LTR, are present at barley centromeres. The preferential (or exclusive)
      localization of an apparently complete retroelement within the centromeric
      regions of several cereal species raises interesting questions about its role in
      karyotype evolution and centromere function.

PMID- 10069079
TI  - Floral dip: a simplified method for Agrobacterium-mediated transformation of
      Arabidopsis thaliana.
AB  - The Agrobacterium vacuum infiltration method has made it possible to transform
      Arabidopsis thaliana without plant tissue culture or regeneration. In the present
      study, this method was evaluated and a substantially modified transformation
      method was developed. The labor-intensive vacuum infiltration process was
      eliminated in favor of simple dipping of developing floral tissues into a
      solution containing Agrobacterium tumefaciens, 5% sucrose and 500 microliters per
      litre of surfactant Silwet L-77. Sucrose and surfactant were critical to the
      success of the floral dip method. Plants inoculated when numerous immature floral
      buds and few siliques were present produced transformed progeny at the highest
      rate. Plant tissue culture media, the hormone benzylamino purine and pH
      adjustment were unnecessary, and Agrobacterium could be applied to plants at a
      range of cell densities. Repeated application of Agrobacterium improved
      transformation rates and overall yield of transformants approximately twofold.
      Covering plants for 1 day to retain humidity after inoculation also raised
      transformation rates twofold. Multiple ecotypes were transformable by this
      method. The modified method should facilitate high-throughput transformation of
      Arabidopsis for efforts such as T-DNA gene tagging, positional cloning, or
      attempts at targeted gene replacement.

PMID- 10069080
TI  - Defending the priority of 'remarkable researches': the discovery of fibrin
      ferment.
AB  - At times scientists manipulate their community's perception of scientific
      discoveries. The following case study illustrates the extent to which a
      community's understanding of a discovery was influenced by one of its members. In
      the 1870s the British physiologist Arthur Gamgee undertook a campaign to insure
      Andrew Buchanan of Glasgow credit for his blood clotting research, conducted from
      the early 1830s to the mid-1840s. Gamgee endeavored to establish Buchanan as the
      discoverer of fibrin ferment, a clotting factor first isolated and named in 1872
      by Alexander Schmidt of Dorpat. Gamgee's campaign included the solicitation of
      support for Buchanan from contemporary physiologists, by discussing Buchanan's
      work in his publications and by demonstrating through experimentation that the
      material extracted from Buchanan's washed blood clots was similar, if not
      identical, to Schmidt's fibrin ferment. Gamgee's influence on the scientific
      community's perception of the discovery was effective, and Buchanan is generally
      considered the discover of the clotting factor and Schmidt its rediscovered.
      However, examination of Buchanan's research in blood coagulation and the context
      in which he conducted the research reveals that Buchanan is neither the
      discoverer of fibrin ferment nor even a precursor to Schmidt.

PMID- 10069081
TI  - 'You people': intolerance and alternative medicine.

PMID- 10069082
TI  - 'War' editorial invites varied and visceral reactions.

PMID- 10069083
TI  - 'War' editorial invites varied and visceral reactions.

PMID- 10069084
TI  - 'War' editorial invites varied and visceral reactions.

PMID- 10069086
TI  - 'Voices' reader asserts her soul's individual destiny.

PMID- 10069085
TI  - 'War' editorial invites varied and visceral reactions.

PMID- 10069087
TI  - The Osher Center for Integrative Medicine at UCSF: healing the whole person with
      'relationship-centered' medicine.

PMID- 10069088
TI  - The construct of control in mind-body medicine: implications for healthcare.
AB  - Research suggests that one of the principal reasons patients are attracted to
      alternative medicine is that they find many of these therapies more congruent
      with their philosophical orientation toward health. Many mind-body approaches,
      which are some of the most frequently used classifications of complementary and
      alternative therapies, grow out of research demonstrating the important role of
      psychological factors in treating and preventing illness. This article reviews
      research on one such factor--control--and its importance in health. Studies
      demonstrating the following are highlighted: (1) illness frequently results in
      feelings of loss of control; (2) gaining a sense of control can help patients to
      cope with illness; (3) whereas control may influence physiological function and
      health outcomes, the amount of active control we can exercise over physical
      functioning and health is limited; and (4) it is important to match control
      strategies to patient control styles and preferences. The implications of mind
      body studies are also discussed.

PMID- 10069089
TI  - Seeing to the distant mountain: diagnosis in Tibetan medicine.
AB  - To make use of an ancient traditional medical system, we must first comprehend
      the singular concepts and language that system uses to understand and describe
      health and illness. The diagnostic procedure is the method by which a person's
      medical condition is interpreted into the conceptual framework and language of
      medical science. This article provides a description of traditional Tibetan
      medical diagnosis and explains how a Tibetan physician perceives and analyzes a
      presenting illness. It discusses the spiritual, psychological, and physical
      aspects of the Tibetan medical approach to diagnosis. Addressing these issues can
      help us to understand what is unique about this system of alternative medicine
      and how it can inform other models of medical practice.

PMID- 10069090
TI  - Confronting the communication gap between conventional and alternative medicine:
      a survey of physicians' attitudes.
AB  - CONTEXT: An estimated 60 million Americans use some from of complementary and
      alternative medicine, though approximately 70% do not tell their physicians about
      this use. Open communication between conventional medical providers and patients
      in this area is therefore lacking. OBJECTIVE: To explore the dynamics that could
      potentially contribute to communication breakdown between physicians and patients
      over the use of alternative therapies. DESIGN: Mail-in, self-administered
      questionnaire. PARTICIPANTS: 96 practitioners in primary care and medical
      subspecialties representing the local county medical society, Stark county, Ohio.
      MAIN OUTCOME MEASURES: Data were obtained on the following: (1) physicians' level
      of familiarity with 23 different alternative therapies, (2) the question of
      whether physicians used the therapies themselves, (3) physicians' assessment of
      the potential benefits and harm of each therapy, and (4) physicians' response to
      the prospect of their patients using these therapies. RESULTS: Respondents
      reported the use of myriad alternative therapies. Only 28%, however, referred
      patients for alternative therapies. The physicians demonstrated clear preferences
      for specific therapies (i.e., when asked about benefits, familiarity, and
      reactions to patient use, they responded differently depending on the therapy).
      Indication that the doctor-patient relationship might be terminated as a result
      of alternative therapy use was more common among subspecialists than among
      primary care practitioners. CONCLUSIONS: Overall, physicians demonstrated an open
      attitude toward alternative therapies. This finding indicates that patients
      should disclose their use of alternative therapies to their doctors. Increased
      referral to alternative healthcare providers may require both ongoing peer
      reviewed studies of efficacy and increased physician access to information
      concerning therapies that have undergone definitive study.

PMID- 10069091
TI  - Using hypnosis to accelerate the healing of bone fractures: a randomized
      controlled pilot study.
AB  - CONTEXT: Hypnosis has been used in numerous medical applications for functional
      and psychological improvement, but has been inadequately tested for anatomical
      healing. OBJECTIVE: To determine whether a hypnotic intervention accelerates
      bodily tissue healing using bone fracture healing as a site-specific test.
      DESIGN: Randomized controlled pilot study. SETTING: Massachusetts General
      Hospital, Boston, Mass, and McLean Hospital, Belmont, Mass. PATIENTS: Twelve
      healthy adult subjects with the study fracture were recruited from an orthopedic
      emergency department and randomized to either a treatment (n = 6) or a control
      group (n = 6). One subject, randomized to the treatment group, withdrew prior to
      the intervention. INTERVENTION: All 11 subjects received standard orthopedic care
      including serial radiographs and clinical assessments through 12 weeks following
      injury. The treatment group received a hypnotic intervention (individual
      sessions, audiotapes) designed to augment fracture healing. MAIN OUTCOME
      MEASURES: Radiological and orthopedic assessments of fracture healing 12 weeks
      following injury and hypnotic subjects' final questionnaires and test scores on
      the Hypnotic Induction Scale. RESULTS: Results showed trends toward faster
      healing for the hypnosis group through week 9 following injury. Objective
      radiographic outcome data revealed a notable difference in fracture edge healing
      at 6 weeks. Orthopedic assessments showing trends toward better healing for
      hypnosis subjects through week 9 included improved ankle mobility; greater
      functional ability to descend stairs; lower use of analgesics in weeks 1, 3, and
      9; and trends toward lower self-reported pain through 6 weeks. CONCLUSION:
      Despite a small sample size and limited statistical power, these data suggest
      that hypnosis may be capable of enhancing both anatomical and functional fracture
      healing, and that further investigation of hypnosis to accelerate healing is
      warranted.

PMID- 10069092
TI  - Michael Murray, ND a natural approach to health. Interview by Bonnie Horrigan.

PMID- 10069093
TI  - Music therapy and chiropractic: an integrative model of tonal and rhythmic spinal
      adjustment.
AB  - There is a philosophical basis for the integration of treatment using music
      therapy and chiropractic. Perception is intimately linked to the nervous system.
      A relationship between spinal integrity and consciousness does exist. We can see
      that as spinal distortions diminish and awareness increases, there is a natural
      attraction toward the higher or more loving state of consciousness. Rhythms of
      healing and suffering are a key concept in combining music therapy with
      chiropractic manipulation. Donald Epstein's conceptualization of the rhythmic
      stages of consciousness corresponding to prescribed physiological patterns serves
      as a starting point for the use of rhythm in the healing process. Using
      interactive music, the music therapist can help facilitate a change in the
      patient's physical or emotional state. This occurs when the practitioner
      establishes an initial connection or musical validation of the patient's
      emotional state and assists the healing process by improvising supportive music
      while suggesting possibilities for resolution. We believe that the power of music
      can be used as a significant tool in chiropractic work to aid individuals in
      their healing process.

PMID- 10069094
TI  - European Commission sponsors consensus report on unconventional medicine.
      Research Council for Complementary Medicine.

PMID- 10069095
TI  - Effects of a prayer circle on a moribund premature infant.

PMID- 10069096
TI  - NAMI: a convention worth noting. National Alliance for the Mentally Ill.

PMID- 10069097
TI  - Screening and predicting adolescent depressive symptoms in rural settings.
AB  - Adolescent depression with related suicidal behavior is a serious health problem.
      This article describes depressive symptoms, reported life events, and demographic
      risk factors in 846 rural adolescents. The results indicate that self-reported
      depressive symptoms in rural adolescents is significantly (p < .05) related to
      gender, death in the family, and the perceived positive and negative impact of
      life events, as well as the specific events of losing a close friend, an increase
      in number of arguments with parents, trouble with classmates, and trouble with
      police. The type of school program and trouble with siblings was marginally
      significant (p < .10). These demographic factors and life events may assist
      health-care professionals in identifying adolescents at risk for depressive
      symptoms.

PMID- 10069098
TI  - Effect of abuse on self-perception of rural Mexican-American and non-Hispanic
      white adolescents.
AB  - The prevalence of adolescent abuse has serious community health ramifications
      because of its associated psychological responses. Theoretical frameworks have
      described behaviors arising from interpersonal interactions as being affected by
      self-concept. Therefore, the issue of assessing the self-concept is critical in
      research and practice for understanding the behavior of abused adolescents. This
      research arose from clinical practice in a rural Mexican-American and non
      Hispanic White community. The practice focused on individual and group counseling
      for adolescents in abusive relationships. This study proposed to refine the
      theoretical basis for interventions related to self-concept and woman abuse for
      rural Mexican-American and non-Hispanic White adolescents.

PMID- 10069099
TI  - Care provision and community adjustment of rural consumers with serious mental
      illness.
AB  - The purpose of this study was to examine the predictors of successful community
      living in a sample of rural individuals with severe and persistent mental illness
      (N = 40). Multimeasure/multisource indicators of consumer status, care provider
      attitudes, and care provider support provision were employed to predict community
      adjustment as measured by satisfaction with quality of life. Separate
      semistructured interviews were conducted with consumers, their case manager, and
      a family member or adult home provider. Reliability of the measures was
      established within acceptable limits. The multiple regression analyses showed
      that life stress and informal care-provider attitudes satisfied the inclusion
      criteria. R2 was .61 (F[2, 37] = 29.10, p < .001). Quality-of-life satisfaction
      was predicted primarily by consumer status characteristics.

PMID- 10069100
TI  - Utilization of mental health services among rural elderly.
AB  - Rural elders are an undeserved and vulnerable population with compromised access
      to health and human services leading to premature institutionalization. Even
      though elders living in rural areas have psychiatric illnesses that would prompt
      them to use mental health services, their use of these services remains low. This
      study developed predictive models of psychiatric hospitalization, use of mental
      health services, and use of crisis intervention by rural elders participating in
      an outreach case-management program. A combination of demographic, health status,
      and organizational variables were used in stepwise multiple regression. Being
      married and having supplemental insurance in addition to Medicare predicted 23%
      of the variance for utilization of psychiatric hospitalization. Only one
      variable, Medicaid, predicted 14% of the variance for use of mental health
      services. Type of caregiver, marital status, household composition, and Medicaid
      insurance accounted for 23% of the variance in utilization of crisis intervention
      by rural elders. Overall, the two variables that most likely predicted use of
      psychiatric mental health services were marital status and type of insurance.

PMID- 10069101
TI  - Developmental task achievement and learned resourcefulness in healthy older
      adults.
AB  - Although resourcefulness has been found to promote healthy functioning and is
      believed to be learned throughout life, studies have not examined relationships
      between developmental variables and resourcefulness. This study examined
      Erikson's eight developmental tasks as predictors of learned resourcefulness in
      60 healthy elders. Hierarchical regression based on Erikson's theory revealed
      that 37% of the variance in learned resourcefulness was explained by trust,
      autonomy, initiative, industry, and identity whereas intimacy, generativity, and
      integrity were not significant. The results suggest that mastery of developmental
      tasks through adolescence play a key role in determining how resourceful healthy
      elders are in their daily activities.

PMID- 10069102
TI  - Meanings of state hospital nursing. I: Facing challenges.
AB  - The purpose of this study was to describe the meaning of work for nurses employed
      in two state psychiatric hospitals. Nurses at both hospitals participated in
      designing and carrying out the research. In Phase I, nurses described situations
      in which they had been observers or participant observers and the way that they
      understood what was occurring in the situations described. The data from these
      descriptions were analyzed in collaboration with small groups of nurse co
      investigators at each hospital. In Phase II, patterns of meaning identified in
      Phase I were checked and further refined based on focus groups and interviews
      with nurses at both hospitals. The interrelated dilemmas faced by nurses are
      discussed as (1) challenges in clinical decision making, (2) challenges regarding
      personal control, and (3) challenges of maintaining professional standards. Ways
      of meeting these challenges, coping, and making meaning are discussed in a
      companion article, "Meanings of State Hospital Nursing II: Coping and Making
      Meaning".

PMID- 10069103
TI  - Meanings of state hospital nursing. II: Coping and making meaning.
AB  - The purpose of this study was to describe the meaning of work for nurses employed
      in two state psychiatric hospitals. A companion article, "Meanings of State
      Hospital Nursing I: Facing Challenges", (Archives of Psychiatric Nursing, 13(1),
      48-54), describes the study methods and the findings regarding the challenges in
      clinical decision making, personal control, and maintaining professional
      standards that nurses face in state hospital nursing. This article focuses on the
      ways that nurses meet the challenges, cope, and make meaning. These methods
      include taking pride in being able to cope with the challenges, maintaining
      watchfulness, narrowing of focus, valuing the ideal when it does occur, and
      constructing personal meanings. The article concludes with suggestions for
      supporting and enhancing the ways in which nurses cope and make meaning in their
      daily work in state hospitals.

PMID- 10069104
TI  - [Management in clinical microbiology].

PMID- 10069105
TI  - [Evaluation of the polymerase chain reaction technique for the diagnosis of
      meningitis caused by Neisseria meningitidis and Haemophilus influenzae].
AB  - BACKGROUND: Bacterial meningitis is a severe infection of the central nervous
      system (CNS), most frequently caused by Neisseria meningitidis in our setting.
      Microbiologic diagnosis of bacterial meningitis is not enough sensitive because
      its efficiency can be affected by the therapeutic regimen given to the patient.
      Polymerase chain reaction (PCR) can provide a more sensitive diagnosis and allow
      us to get an earlier result. OBJECTIVES: To assess the sensitivity and
      specificity of a PCR technique for the diagnosis of meningitis caused by N.
      meningitidis and Haemophilus influenzae. MATERIAL AND METHODS: Ninety-six
      patients who were attended because of suspected bacterial meningitis on the
      Hospital de Sant Joan de Deu, Corporacio Sanitaria Parc Tauli and Hospital de la
      Santa Creu i Sant Pau, and had negative results by conventional laboratory
      methods, were selected for the study. A total of 99 cerebrospinal fluid samples
      (CSF) were obtained and evaluated for PCR. DNA extracts of the CSF samples were
      amplified by universal primers. Amplification products were hybridized with
      specific probes for Haemophilus genus and N. meningitidis. Positive and negative
      controls were included to asses the reliability of PCR. RESULTS: Eight of the 99
      CSF samples (8%) were positive by PCR and subsequent hybridization with the
      specific probe of N. meningitidis. None of the amplicons hybridized with the
      probe of Haemophilus genus. Thirteen percent of the patients (8/59) with clinical
      suspicious of non-neonatal sepsis or meningitis were diagnosed by PCR, amongst
      them, 36% of the cases (4/11) with initial diagnosis of meningococcal sepsis or
      meningitis. CONCLUSIONS: The sensitivity and the specificity of the PCR technique
      afford a complementary method to conventional ones, in special for the diagnosis
      of meningococcal meningitis in the group of pediatric patients.

PMID- 10069106
TI  - [Distribution of Salmonella spp. serotypes isolated in Spain during a 4-year
      period (1993-1996)].
AB  - BACKGROUND: Knowledge of the epidemiology of salmonellosis over time is the main
      tool for public health care control of this disease which is the main cause of
      alimentary toxic infections in Spain. The epidemiologic marker of choice in this
      genus is the stable, simple technique of serotyping, which, given its wide use
      allows the follow up of the main serotypes over the years. This study analyzes
      the seasonal trends of the main serotypes of Salmonella received in the National
      Reference Laboratory of Salmonella and Shigella in Spain (LNRSSE) from 1993-1996.
      MATERIALS AND METHODS: Serotyping of the strains of Salmonella received in the
      LNRSSE during the years of the study with sera induced in our laboratory and
      commercial laboratories was undertaken. The strains of human origin the trends of
      the main serotypes were evaluated with the Mantel-Haenszel chi 2 test. RESULTS
      AND DISCUSSION: Nineteen thousand seven hundred forty-one strains of Salmonella
      from most of the autonomous communities of Spain were analyzed. Ninety-two point
      one two percent of the strains of human origin were received from laboratories
      that sent strains throughout at least three of the four years of the study,
      thereby allowing evaluation of the serotype trends for this group of strains. The
      enteritidis and typhimurium serotypes were the most frequently observed. In these
      serotypes the strains of human origin were typed with double the frequency of
      that found among those from food and three-fold greater than that found among the
      strains of environmental origin. Typhimurium was the more frequently found than
      enteriditis in the group of strains from diseased animals. Finally, the
      significant statistical increase of the hadar serotype, which surpassed the
      virchow serotype in recent years, is of note.

PMID- 10069107
TI  - [Cat-scratch disease: series of 14 cases. The diagnostic usefulness of serology].
AB  - BACKGROUND: Disease by cat scratch (CSD) is a syndrome characterized by regional
      adenopathies following cat scratch or bite. Despite knowing the etiologic agent
      of the same, there is still controversy in the diagnosis of the syndrome in daily
      clinical practice. MATERIALS AND METHODS: The cases of CSD diagnosed from 1990 to
      1997 with positive serology for Bartonella henselae performed by indirect
      immunofluorescence were reviewed. RESULTS: In 13 out of the 14 patients studied
      direct contact with cats was reported. Lymph node involvement corresponded to the
      following regions: axillary (57%), inguinal (28%), epitroclear (21%), cervical
      (14%), and periauricular (7%). In 35% of the cases, several territories were
      involved. In 3 patients the adenopathies were fluctuating. Eleven
      anatomopathologic studies were performed with 6 diagnoses of granulomatous
      adenitis, 3 reactive adenitis and 2 purulent adenitis. The serology for
      Bartonella henselae was positive in all the patients with a range of 1/64-1/256.
      The evolution was favorable in all the patients. DISCUSSION: Interpretation of
      the results of serology should be cautions and always related to the clinical and
      epidemiological picture of the patient. This technique should be considered as
      another criteria in the diagnosis of cat scratch disease to the detriment of the
      cutaneous test.

PMID- 10069108
TI  - [HIV infection in the health care are of Leon. Incidence from 1983-1997].
AB  - BACKGROUND: The aim of the present work was to know the incidence of HIV
      infection in the sanitary area of Leon, and its tendency, throughout the period
      1983-1997. MATERIAL AND METHODS: A register of cases with the patients attended
      in the area hospitals, those detected in the Penitentiary Centre of Leon and
      notifications of cases of AIDS at a national level have been used. Only the
      patients residing in a municipality belonging to the area at the time of
      detection of the infection have been included. Age, sex, risk group, year of
      detection of the infection, development to AIDS and mortality were analysed. The
      Spearman coefficient correlation range has been used for the study of tendency.
      RESULTS: 509 cases of HIV infection (374 males and 134 females) were detected in
      the area from 1983 to 1997. The accumulated incidence throughout the period of
      study was 1,368/million inhabitants. The annual incidence shows and upward phase
      until 1990, followed by another of plateau (1990-1993). In 1994-1995 there was a
      decrease, interrupted in 1996-1997. The curve as a whole doesn't reveal a
      descending tendency (p > 0.05). The annual incidence in the IDU follow a similar
      pattern to that of the complete group while the group of heterosexual
      transmission shows a tendency to increase (p < 0.025). 223 patients (43.8%)
      developed AIDS, 195 of whom we know the evolution. Of these, 139 have died and 56
      are still alive. CONCLUSIONS: There is no evidence that the incidence of HIV
      infection tends to decrease in the sanitary area of Leon at present. This is
      probably related to the behaviour of the two main risk groups: a tendency to
      stability in the case of IDU and to increase in heterosexual transmission. It is
      important to insist on the prevention campaigns, especially those directed
      towards avoiding heterosexual transmission.

PMID- 10069109
TI  - [Sensitivity of group A beta-hemolytic Streptococcus isolated from pediatric
      pharyngotonsillitis to erythromycin and clarithromycin: a primary care
      multicenter study].
AB  - BACKGROUND: The recent increase in the prevalence of macrolide-resistant group A
      beta-haemolytic Streptococcus (BHSGA) strains reported in some areas in Spain and
      several neighboring countries underscores the need to perform a periodic
      surveillance, with the adequate methodology, of the level of its susceptibility
      to these antimicrobials which are frequently used in our country for the
      treatment of acute streptococcal pharingotonsillitis and respiratory tract
      infections. PATIENTS AND METHODS: The susceptibility of 293 isolates of BHSGA to
      the macrolides erythromycin and clarithromycin was evaluated by the broth
      microdilution procedure recommended by the NCCLS (1997). The isolates were
      prospectively obtained from children with acute pharyngotonsillitis (n = 757) who
      were seen at primary care centers in ten Spanish cities. RESULTS: An overall
      prevalence of 8.9 and 7.8% erythromycin- and clarithromycin-resistant BHSGA
      isolates was respectively found. The percentage of resistant isolates varied
      considerably among the different cities subjected to study (0-33%). Overall, the
      intrinsic activity of clarithromycin (MIC50 and MIC90 of 0.007 and 0.25 mg/ml,
      respectively) was slightly higher than that of erythromycin (MIC50 and MIC90 of
      0.015 and 0.5 mg/ml, respectively). All strains studied were uniformly
      susceptible to penicillin. CONCLUSIONS: Macrolide antibiotics, erythromycin and
      clarithromycin, continue to be highly active against BHSGA. The mean level of
      resistant strains found in Spain from community acquired infections and recovered
      prospectively is comparable to that of our neighboring countries.

PMID- 10069110
TI  - [PCR in the diagnosis of focal cerebral lesions in HIV infected patients].

PMID- 10069111
TI  - [Necrotizing cellulitis of the hand and forearm in a hospitalized diabetic
      patient].

PMID- 10069112
TI  - [Mediastinal adenopathies and peripheral arteritis].

PMID- 10069113
TI  - [Multivalvular endocarditis caused by Pseudomonas aeruginosa in a patient
      infected with the human immunodeficiency virus].

PMID- 10069114
TI  - [Bacteremia caused by Stomatococcus mucilaginosus in a neutropenic patient].

PMID- 10069115
TI  - [Hemophagocytic syndrome associated with tuberculosis in a patient infected with
      the human immunodeficiency virus].

PMID- 10069116
TI  - [Late recurrence of endocarditis caused by Coxiella burnetii following prosthetic
      valve substitution and prolonged antibiotic treatment].

PMID- 10069117
TI  - [Ticks and Lyme disease in Lanzarote].

PMID- 10069118
TI  - [Meningitis by Streptococcus pneumoniae: resistant to cefotaxime?].

PMID- 10069119
TI  - [Abdominopelvic actinomycosis in an intrauterine device carrier: treatment with
      ceftriaxone].

PMID- 10069120
TI  - [Hydronephrosis caused by indinavir].

PMID- 10069121
TI  - [Enterobacter agglomerans pneumonia outside of the hospital in a previously
      health patient].

PMID- 10069122
TI  - [Are multiple sclerosis, gastric dyspepsia, asthma, atherosclerosis...infectious
      diseases?].

PMID- 10069123
TI  - Spinocerebellar ataxia genes--expansion of the phenotype.

PMID- 10069124
TI  - The National Meningococcal Reference Laboratory.

PMID- 10069125
TI  - Medical management of disturbed behaviour.

PMID- 10069126
TI  - No show is a major problem in planning appointments for infertility patients.
AB  - We examined the pattern of bookings for and actual visits undertaken by patients
      attending the Infertility Clinics at the Rotunda Hospital Dublin as well as the
      accuracy of systems in place for recording such events. The data provided by the
      Hospital Patient Administration System (PAS), clinic worksheets and clinic record
      chart of first visit couples attending initially over a 12 month period 1995/1996
      and their subsequent records to February 1998 was analysed. Comparable figures
      were provided from the corresponding private clinic over the same time frame.
      Sixty-nine percent had already had investigations and treatment elsewhere.
      Discrepancies were noted between the PAS and manual systems as confirmed by the
      patient records. The manual proved more accurate. We found 32% (88 of 276)
      patients failed to turn up for a first appointment compared with 17% of private
      patients. Un-notified no-show provides great logistic difficulties in planning
      clinic management. Waiting lists grow, staff and patients alike are greatly
      inconvenienced. This apparent recklessness makes the Charter of Rights for
      Hospital Patients difficult to comply with. A possible answer is to demand
      reconfirmation near to the clinic date and in it's absence reassign the
      appointment to another. Population education is clearly needed.

PMID- 10069127
TI  - The management of coeliac disease.
AB  - One hundred children put on a gluten free diet because of suspected coeliac
      disease were followed for a mean period of 9.9 years. The diagnosis was
      eventually confirmed in 53. Under the age of two, 35 children showed subtotal
      villous atrophy in their initial biopsy but nine of these on subsequent gluten
      challenge and rebiopsy were found to tolerate gluten normally. Challenge and
      rebiopsy are also necessary for children over the age of two where the initial
      biopsy changes are less severe than subtotal villous atrophy. Such challenges can
      probably be carried out earlier than the recommended age of six given in the 1990
      ESPGAN (European Society for Paediatric Gastroenterology and Nutrition) report
      with little risk of serious dental damage.

PMID- 10069128
TI  - Effect of the British warning on contraceptive use in the General Medical Service
      in Ireland.
AB  - In October 1995 the UK Committee of Safety of Medicine (CSM) issued a warning
      about the safety (thromboembolic disease) of the third generation oral
      contraceptive steroids (OCS) recommending a switch to older agents except where
      women were intolerant of first and second generation OCS. Advice by the Irish
      regulatory authority (Irish Medicines Board) did not recommend such a switch.
      This pill scare lead to some UK users stopping OCS mid-cycle and a rise
      subsequently in abortions and pregnancies was noted. To determine whether local
      or UK advice was followed we obtained data from the General Medical Service (GMS)
      Scheme on the use of contraceptive steroids prescribed before and after the CSM's
      warning. The results show a clear shift from usage of the third generation OCS to
      the second generation OCS and norgestimate-containing OCS. We have also noted a
      marked fall in the overall use of the combined OCS, a trend that was noted in the
      U.K. It is clear that prescribers and pill users were influenced more by advice
      from the UK than by Irish regulatory authority. There is now a centralised
      European mechanism to licence drugs in the European Union (EU). We need to
      develop an EU perspective to issues of drug safety, as constituent nations are no
      longer isolated islands.

PMID- 10069129
TI  - The prevalence of asthma in schoolboys of travellers' families.
AB  - This study compared the prevalence of asthma in travelling schoolboys and settled
      controls to determine whether the travelling lifestyle may be a protective factor
      in the development of asthma. Information was collected by parental responses to
      the ISAAC (International Study of Asthma and Allergies in Childhood)
      questionnaire. The design was a cross-sectional study with descriptive and
      analytical components. The subjects were six to twelve year old schoolboys from
      all male travelling children in Cork and from a selection of settled schoolboys.
      In addition the study collected information on the predictor variables--age,
      passive smoking and number of siblings. The questionnaire was administered to 54
      travelling boys and 129 controls. The parent reported prevalence of wheeze and
      related symptoms were all more common in controls compared with the travelling
      boys. The values were significant for wheeze in the last year (31.3% v 14.8%; OR
      5.6, p = 0.025), and for doctor diagnosed asthma (25.6% v 11.1%; OR = 5.1, p =
      0.04). Schoolboys from travelling families have less wheeze and doctor diagnosed
      asthma than controls. The experience of the travelling lifestyle maybe a
      protective factor in the development of asthma.

PMID- 10069130
TI  - Do doctors benefit from their profession?--A survey of medical practitioners'
      health promotion and health safety practices.
AB  - Three hundred Irish Medical Organisation members were surveyed on health
      promotion and health and safety issues. 64.7% responded (65.3 males; 33.7% <
      thirty-five years). Over half (54.9%) were aware of the safety legislation and
      very few reported available occupational health services. A majority wanted more
      such services. Nearly all believed health promotion was important yet only 35.2%
      always availed of opportunities to give such advice. 36.3% were often stressed,
      particularly at work. Alcohol was sometimes or frequently used to cope by around
      half of respondents. Although less than half (47.7%) used whole milk, one third
      usually or always added salt to their food. 15.5% took no weekly aerobic exercise
      but 42.0% claimed to do so three times weekly. 11.4 were current smokers. A third
      of women had never had a cervical smear. We conclude doctors require adequate
      occupational health services.

PMID- 10069131
TI  - Teenage pregnancy in the Rotunda Hospital.
AB  - The primary aim of this study was to investigate obstetric outcomes in teenagers
      delivered in the Rotunda Hospital and to identify whether younger teenagers have
      a poorer obstetric outcome. Delivery record details were recorded from the years
      1992-96. These included the number of teenage mothers, maternal age, parity,
      gestation, mode of delivery, birth weight and Apgar scores. Teenagers were
      classified into those aged under 17 years and those aged 17 and over. Overall
      2,228 teenage mothers were delivered in the Rotunda hospital, representing 17.2%
      of the total teenage population delivered in Ireland during the study period. Ten
      percent of mothers were under 17 years; 10.6% were multiparous with 2.6% of these
      under 17 years. There was a significant difference in the preterm delivery rate
      when the teenagers were compared as a whole with matched controls aged 20-24
      years (p = 0.0411). However this did not translate into a poorer neonatal outcome
      as on average only 5% of babies were low birth weight and only 3% had Apgar
      scores < 3. Overall 70.2% of deliveries were spontaneous, 20.2% were
      instrumental. Less than 10% of deliveries were by caesarean section. However the
      rate of caesarean section increased with age from 14 (5.7%) to 19 (13.5%) years
      and this trend was statistically significant (p = 0.013). In conclusion, this
      study does not support the view that younger teenage mothers have a poorer
      obstetric and neonatal outcome. It has also been shown that there has been a
      large increase in the number of multiparous patients in this teenage population.

PMID- 10069132
TI  - The issue of informed consent in medical law.

PMID- 10069133
TI  - Hospital admission with childhood asthma--recent trends.

PMID- 10069134
TI  - Adult abdominal migraine and sumatriptan: a case report.

PMID- 10069135
TI  - Sulphasalazine induced agranulocytosis revisited.

PMID- 10069136
TI  - Normal developmental outcome following exposure and hypothermia in a new-born
      infant.

PMID- 10069137
TI  - Assessing behavioral health outcomes in outpatient programs: reliability and
      validity of the BASIS-32.
AB  - The Behavior and Symptom Identification Scale (BASIS-32) was developed to assess
      mental health outcomes among patients with severe illness treated on inpatient
      programs. However, its applicability and utility to those treated in outpatient
      programs has not been determined. The objective of this study was to assess
      reliability, validity, and sensitivity to change of the BASIS-32 among mental
      health consumers treated in outpatient programs. A total of 407 outpatients
      completed the BASIS-32 and the Short Form Health Status Profile (SF-36) at the
      beginning of a treatment episode and again 30 to 90 days later. Outpatients
      reported less difficulty at intake than did inpatients, and the BASIS-32 detected
      statistically significant changes 30 to 90 days after beginning outpatient
      treatment. Factor structure and construct validity were partially confirmed on
      this sample of outpatient consumers. Analyses of data from a wide range of
      facilities and samples would add to validation efforts and to further refinement
      of the BASIS-32.

PMID- 10069138
TI  - Implementing outcome systems: lessons from a test of the BASIS-32 and the SF-36.
AB  - With increasing pressure from third-party payers to assess client outcomes,
      clinical programs want to know how to implement outcome systems. This article
      focuses on practical and logistic questions involved in implementing an outcome
      assessment system in ambulatory behavioral healthcare settings. Study questions
      addressed outcome systems in general and the use of the Behavior and Symptom
      Identification Scale (BASIS-32) and the Short Form Health Status Profile (SF-36)
      in particular. General questions focused on obtaining provider buy-in, client
      consent and confidentiality, data collection methods, sampling, time points,
      maximizing client participation, clinical utility of outcome data, and resources
      needed for outcome assessment. Measure-specific questions focused on client
      acceptability of the instruments and applicability of measures to diverse
      populations. The article suggests several strategies for enhancing outcome
      assessment efforts and concludes that there remains a need for further
      understanding of ways to maximize the utility and value of outcome measurement.

PMID- 10069139
TI  - An analysis of drug abuse policies in teaching hospitals.
AB  - The Drug-Free Workplace Act of 1988 mandated written drug abuse policies for
      recipients of certain government grants and contracts. The literature has
      reported costly side effects of employee drug abuse such as decreased
      productivity and increased use of health benefits. Furthermore, litigation
      involving drug abuse policies has been increasingly won by employers. More than
      90% of Fortune 1000 companies have adopted formal drug abuse policies. Using
      content analysis techniques, the current study examined the written substance
      abuse policies of 30 large American teaching hospitals. Results showed
      substantial variation in the style and content of the policies. In general,
      language used in the policies was vague. The study cites the potential use of
      strategic ambiguity in the development of the policies.

PMID- 10069140
TI  - Barriers and facilitators to use of services following intensive family
      preservation services.
AB  - The primary caregivers of 101 families that used short-term, intensive home-based
      services were interviewed 2 months after the services to ascertain use of the
      recommended aftercare services, perceived barriers to service use, and perceived
      facilitators of service use. While 88% of the families accessed at least some of
      the recommended services, more than 50% failed to access all of the recommended
      aftercare services. The most often noted barriers to service use were enabling
      factors at the agency or community level. Yet, many of the services were used,
      and the respondents indicated that professionals played a role in helping them
      link to services. Researchers should continue to study the use of recommended
      aftercare services and the relationship between aftercare service use and
      clinical outcomes.

PMID- 10069141
TI  - Measuring treatment outcomes and client satisfaction in a partial hospitalization
      program.
AB  - Mental health practitioners are increasingly being called on to evaluate the
      effectiveness of the treatment they provide. The partial hospitalization
      component of the mental health industry also has felt this call for outcome
      research. This article presents the results of one program's attempts to answer
      that call through an assessment of treatment outcome and client satisfaction at a
      partial hospitalization program. Participants (N = 287) were evaluated at
      admission, discharge, and 3-month follow-up. The article outlines the procedures
      used for assessment and uses the results as an example of the type of data that
      can be obtained through outcomes measurement. The article is intended to provide
      an example of program evaluation that is easy and inexpensive to administer.

PMID- 10069142
TI  - Self-regulating service delivery systems: a model for children and youth at risk.
AB  - A conceptual model of self-regulating service delivery is proposed for use by
      governments, planners, and policymakers to help children reach optimal adult
      functioning. It addresses most problems of present service delivery and is
      applicable to children in the general population and registered consumers of
      mental health, child welfare, special education, drug dependency, and juvenile
      justice (young offender) services. It has four essential components: (1) outcome
      measurements that reflect the mental health statuses of children in services and
      in the general population; (2) regular feedback of these measurements to
      governments, the public, and service delivery organizations; (3) powerful and
      significant rewards and incentives for the most desired outcomes to increase
      their salience and to motivate provider behavior; and (4) decision making that
      can affect all entities that contribute to the health of children. The evaluable
      expected benefits are improved mental health for children and greater efficiency
      within the "system."

PMID- 10069143
TI  - On-site primary care and mental health services in outpatient drug abuse
      treatment units.
AB  - Providing health services to drug abuse treatment clients improves their
      outcomes. Using data from a 1995 national survey of 597 outpatient drug abuse
      treatment units, this article examines the relationship between these units'
      organizational features and the degree to which they provided onsite primary care
      and mental health services. In two-stage models, Joint Commission on
      Accreditation of Healthcare Organizations-certified and methadone programs
      delivered more on-site primary care services. Units affiliated with mental health
      centers provided more on-site mental health services but less direct medical
      care. Units with more dual-diagnosis clients provided more on-site mental health
      but fewer on-site HIV/AIDS treatment services. Organizational features appear to
      influence the degree to which health services are incorporated into drug abuse
      treatment. Fully integrated care might be an unattainable ideal for many such
      organizations, but quality improvement across the treatment system might increase
      the reliability of clients' access to health services.

PMID- 10069144
TI  - Cost of employee assistance programs: comparison of national estimates from 1993
      and 1995.
AB  - The cost and financing of mental health services is gaining increasing importance
      with the spread of managed care and cost-cutting measures throughout the health
      care system. The delivery of mental health services through structured employee
      assistance programs (EAPs) could be undermined by revised health insurance
      contracts and cutbacks in employer-provided benefits at the workplace. This study
      uses two recently completed national surveys of EAPs to estimate the costs of
      providing EAP services during 1993 and 1995. EAP costs are determined by program
      type, worksite size, industry, and region. In addition, information on program
      services is reported to determine the most common types and categories of
      services and whether service delivery changes have occurred between 1993 and
      1995. The results of this study will be useful to EAP managers, mental health
      administrators, and mental health services researchers who are interested in the
      delivery and costs of EAP services.

PMID- 10069145
TI  - Impact of travel distance on the disposition of patients presenting for emergency
      psychiatric care.
AB  - For veterans presenting for emergency psychiatric care, this research tested the
      hypothesis that patients with poor geographic accessibility to ambulatory mental
      health services would be more likely to be hospitalized. Logistic regression
      results indicated that distant patients (> 60 miles) were 4.8 times more likely
      (p < .05) to be admitted for acute psychiatric treatment than were proximal
      patients (< 60 miles), controlling for clinical and demographic case-mix factors.
      This finding suggests that the Department of Veterans Affairs might be less
      effective in its effort to substitute intensive outpatient care in place of
      expensive inpatient treatment for rural veterans with emergent mental health
      problems.

PMID- 10069146
TI  - Measuring quality of care at life's end.

PMID- 10069147
TI  - Research agenda for developing measures to examine quality of care and quality of
      life of patients diagnosed with life-limiting illness.
AB  - Despite the universality of dying, research has not focused on developing
      conceptual models and measurement tools for examining the quality of care and
      quality of life of dying patients and their loved ones. We present here a vision
      and research agenda for the development of a Tool Kit of Instruments to Measure
      End of Life Care (TIME). Instruments for inclusion in the eventual "Tool Kit"
      should be patient-focused and family-centered, clinically meaningful,
      administratively manageable, and psychometrically sound. Prioritizing domains to
      measure quality of care should be based on consumer input and synergistic with
      ongoing efforts to formulate guidelines and standards of care. For this
      vulnerable population, research is needed regarding the timing and sources of
      data collection. In order to achieve maximal benefit, ultimately measurement
      tools must be incorporated into existing measurement systems and consideration be
      given to generating informative reports which leads to institutional action to
      improve the quality of care.

PMID- 10069148
TI  - Conceptual models and the outcomes of caring.
AB  - Conceptual models and the taxonomies associated with them are inherent tools of
      goal-directed activity. Conceptual models partition reality, discerning
      differences within a phenomenologic continuum; a process that is a fundamental
      requisite for measurement. This paper presents theoretical observations regarding
      the influence of conceptual models on goal-directed endeavors and explores
      specific implications for outcome measurement in palliative care. The dominant
      model of end-of-life care is the problem-based model of adult medicine. In
      clinical orientation, hospice and palliative care bear strong similarities to a
      pediatric and family medical model for early childhood care. This essay examines
      salient features of a conceptual model for palliative care that draws on a life
      cycle or developmental model of human experience in critical transitions and
      explores application of this model to palliative care.

PMID- 10069149
TI  - The concept of quality of life of dying persons in the context of health care.
AB  - Considerable research has addressed quality of life and quality of care; however,
      it has not addressed adequately the experiences of patients and their families at
      the end of life. Health care may have a greater effect on quality of life during
      the dying process than it normally does. Building on research and expert review,
      a conceptual framework is presented that specifies and integrates quality of life
      and quality of health care indicators. Five main concepts include patient/family
      context, structure of care, process of care, satisfaction with care, and quality
      and length of life. Patient and family perspectives are considered. The framework
      emphasizes quality of life, thus detailed definitions of each quality of life
      domain are provided. The goal is to facilitate development of a comprehensive set
      of measures to describe the quality of life of dying persons and evaluate the
      care they receive, to be used to improve end-of-life care.

PMID- 10069150
TI  - For every numerator, you need a denominator: a simple statement but key to
      measuring the quality of care of the "dying".
AB  - A mathematical rate is composed of a numerator, denominator, and time period of
      observation. Deciding who is in the denominator is a key, yet difficult task
      given the blurred boundaries of chronic illness, in examining the quality of care
      for dying patients. We propose two potential solutions. First, one could
      prospectively define the outcome state of "living with life-threatening" illness,
      where there is life expectancy of 1 or 2 years. Second, retrospective interviews
      could be used with family members or other loved ones about their perceptions of
      the quality of care in the last weeks of life. Improving the quality of care for
      dying patients and their families requires attention to this matter.

PMID- 10069151
TI  - Methodological challenges for measuring quality of care at the end of life.
AB  - Measurement is a fundamental step in improving the quality of care for dying
      patients and their families. Yet, there are important methodological challenges
      to be addressed. In conducting surveys about the patient and family experience,
      research is needed regarding the relative merits and cost-effectiveness of
      prospective or retrospective surveys after the patient's death. Proxies are an
      important source of information given that the majority of patients can not be
      interviewed in the last week of life. Research is needed to understand who is
      best able to serve as a proxy and the validity of their reports. The cost
      effectiveness and comparability of alternative data collection strategies need to
      be examined. These and other important issues need to be addressed in designing
      reliable, valid, and clinically manageable measures.

PMID- 10069152
TI  - Acts of omission and commission in pain management: the ethics of naloxone use.
AB  - In this paper the under-use of opioids for pain and symptom management is
      considered by explored by examining the history of the use of the opioid
      antagonist, naloxone.

PMID- 10069153
TI  - Phantom limb pain: a review of the literature on attributes and potential
      mechanisms.
AB  - This study presents a review of the literature on the attributes and potential
      mechanisms involved in phantom limb pain, encompassing studies describing pain in
      the residual limb, phantom sensation and phantom limb pain, and the difficulties
      that may arise when making these distinctions. A variety of theories have been
      proposed to explain causal mechanisms for phantom limb pain. Conceptually,
      research into phantom limb pain is informed by the particular theory of chronic
      pain that is dominant at the time the research is undertaken. For example, early
      physiological theories on the etiology of phantom limb pain were grounded in
      specificity or pattern theories of pain. Later physiological research was based
      on the framework provided by Gate Control Theory and focused on identifying
      peripheral, spinal, and central neural mechanisms. Psychological explanations
      were grounded in psychoanalytic or personality theories of chronic pain which
      propose that phantom limb pain results from pre-amputation psychological
      disturbance. Despite numerous studies examining phantom limb pain, much of this
      research has both conceptual and methodological shortcomings. As such, the
      application of these research findings to clinical practice has limited utility.

PMID- 10069154
TI  - Case presentation: contracting for chronic pain relief.

PMID- 10069155
TI  - Commentary: contracts, opioids, and the management of chronic nonmalignant pain.

PMID- 10069156
TI  - Commentary: promoting ethical flexibility.

PMID- 10069157
TI  - Doctors and insurers.

PMID- 10069158
TI  - Lockerbie and Dunblane: disasters and dilemmas.

PMID- 10069159
TI  - Cancer: proving the causal link, tobacco radiation and environmental pollution.

PMID- 10069160
TI  - Parent Alienation syndrome: what the legal profession should know.

PMID- 10069161
TI  - [Ultrasonic evaluation of endometrial changes induced by cyclic sequential
      hormone substitution therapy].
AB  - BACKGROUND: At present the hormonal replacement therapy on postmenopausal women
      with uterus needs the use of progestins additionally to estrogens, to eliminate
      the risk of endometrial hyperplasia and carcinoma connected with the use of
      estrogens alone. The check of the endometrium during these therapies can be made
      by transvaginal ultrasound that permits the evaluation of the thickness,
      structure, and contour of the endometrial rima. The aim of this study was to
      establish the changes of endometrial thickness during cyclic sequential hormonal
      replacement therapy on healthy postmenopausal women with transvaginal ultrasound.
      METHODS: The endometrial thickness with transvaginal ultrasound has been
      evaluated during the cyclic sequential hormonal replacement therapy on 20 healthy
      women in physiological menopause before the treatment, during the phase of
      treatment with estrogens alone and during the phase of treatment with the
      addition of the progestins. RESULTS: Significant differences during the
      estrogenic phase compared to before treatment have been underlined (5.7 mm vs 3.5
      mm p = 0.002), but not during progestinic phase compared to estrogenic (6 mm vs
      5.7 mm p = 0.712). CONCLUSIONS: Transvaginal ultrasound is a useful investigation
      to evaluate the modifications of the thickness and structure of the endometrium
      during hormonal replacement therapy and can help early diagnosis of endometrial
      diseases during these treatments.

PMID- 10069162
TI  - [Laser surgery in the conservative management of vaginal intraepithelial
      neoplasms].
AB  - BACKGROUND AND AIMS: The increase finding of vaginal intraepithelial neoplasia
      (VaIN) in young women has led to the need to develop personalized conservative
      treatment. The authors studied the use of CO2 laser in the treatment of VaIN,
      evaluating the efficacy, repeatability, complications and the conservation of
      sexual function. METHODS: A total of 37 consecutive patients with histologically
      demonstrated VaIN (10 VaIN 1, 14 VaIN 2 and 13 VaIN 3): mean age 45.3 years,
      37.8% aged < 35 years, 20/37 in childbearing age; VaIN was isolated in two
      patients, synchronous in 22 and in 13 cases it was metachronous with other
      intraepithelial or invasive genital neoplasia. 30/37 patients were treated with
      laser surgery as outpatients for a total of 41 operations (37 vaporisations and
      four excisions) using colposcopic guided CO2 laser with a constant emission power
      of 35 watts or 30 watts in the pulsed mode, under local anaesthesia, following
      the application of 5% acetic acid. RESULTS: Twenty-one (87.5%) of the 24 patients
      evaluated at 12 months were negative after one (16 patients) or more treatments
      (from 2 to 5 in 5 patients). Following the second recidivation, one elderly
      patient preferred traditional demolitive surgery; 2 patients are still awaiting
      further laser surgery. Five patients with multifocal lesions associated topical
      treatment with 5-fluorouracil. None of the sexually active patients complained of
      dyspareunias after treatment. CONCLUSIONS: Given the lack of other equally
      effective treatment and with the aim of preserving genital integrity, the authors
      regard laser surgery as the elective treatment for VaIN 2 and 3.

PMID- 10069163
TI  - [Use of methotrexate in ectopic pregnancy. Results in 55 patients treated].
AB  - BACKGROUND: The opportunity of conservative therapeutic approaches for the
      treatment of ectopic pregnancy diagnosed early with the use of transvaginal
      ultrasound. A number of papers came out in the last 15 years, showing successful
      medical therapies for ectopic pregnancies using methotrexate (MTX) in particular,
      an analog of folic acid with particular tropism for the trophoblast. METHODS: In
      this retrospective study, the results of 55 consecutive cases of tubaric
      pregnancy, treated by endovenous administration of 50 mg/m2 MTX, are presented.
      RESULTS: The percent of global success was 91% (50/55 patients). A single dose of
      MTX was able to resolve the tubaric pregnancy in 48 women (89%), while a second
      administration was necessary in the other seven cases. The percent of success was
      complete (100%) in patients with six weeks of amenorrhea; these values drop to
      72% in patients with seven-eight weeks of amenorrhea; in fact in 5 patients there
      was a tubal damage. CONCLUSIONS: The results obtained show the possibility to
      treat electively with MTX patients with ectopic pregnancy at six weeks of
      amenorrhea, and with good possibilities to save the tubaric patency. For patients
      with a longer amenorrhea the therapy with MTX remains alternative.

PMID- 10069164
TI  - [Premature membrane rupture. Comparison of diagnostic tests].
AB  - BACKGROUND: Objective of this study was to evaluate the accuracy of the vaginal
      pH-test, the Fern-test, the research of foetal cells and of foetal fibronectin in
      vaginal discharge, which are used to diagnose premature rupture of membranes.
      METHODS: To this aim 40 pregnant patients between 24th and 37th weeks gestation
      have been examined, considered at risk for sub-clinic loss of aminiotic fluid: 23
      were affected by preterm labour and 17 by suspected rupture of membranes.
      RESULTS: Subsequently amniotic sac was confirmed to be ripped in 10 cases (25%):
      2 (8.7%) in the 23 patients with preterm labour, and 8 (47%) in the 17 patients
      with suspected PROM. Sensibility, specificity and accuracy were respectively: 70,
      97 and 90% for pH-test; 70, 100 and 93% for Fern-test; 50, 93 and 82% for foetal
      cells; 100, 90 and 93% for fibronectin test. CONCLUSIONS: In personal experience
      fibronectin test appeared to be the most sensible and accurate marker. Fern-test
      was the most specific, while the research of foetal cells appeared to be the
      least reliable.

PMID- 10069165
TI  - [Sarcoma of the endometrial stroma].
AB  - BACKGROUND: To evaluate the most important risk factors and the efficacy of
      endometrial stromal sarcoma therapy. METHODS: During a period of 9 years, 5 cases
      of ESS have been observed at the IInd Obstetrical and Gynecological Institute of
      the University of Bari. The patients were staged according to the FIGO
      classification of endometrial carcinoma and studied from an epidemiological,
      histopatological and clinical point of view. All patients firstly received
      uterine courettage and then total simple laparohysterectomy. In 4 cases bilateral
      salpingo-oophorectomy and then polychemotherapy. Only in 1 case total
      hysterectomy and monolateral salpingo-oophorectomy were performed. RESULTS: Two
      patients were affected by low grade ESS malignancy respectively at Ib and Ic
      stage and received only surgery. High grade ESS malignancy was diagnosed in 3
      patients at stage IIIa and they received surgery followed by chemotherapy. These
      3 patients survived for 14, 25 and 30 months. The other two are still alive, with
      no evidence of the disease at 25 and 36 months. CONCLUSION: ESS is a rare
      neoplasm; the low grade malignancy may survive from 80-100%, while the high ones
      can have a fatal prognosis with exitus in 12-30 months.

PMID- 10069166
TI  - [Hardiness test in obstetrics. Behavior of the pregnant woman facing the stress
      of labor and delivery].
AB  - BACKGROUND: Evaluation of the hardiness test, already used to evidentiate the
      ability to face the stress, among women in pregnancy, in order to evaluate the
      possibility to face the stress of labor and delivery. METHODS: The test has been
      used in 67 normal pregnant women, with gestational age between the 32th and 36th
      week of gestation. The value of the hardiness test in the three components of
      "Challenge", "Control", and "Commitment" has been evaluated. These indexes have
      been correlated with the modality of delivery, age, choice of epidural analgesia,
      fetal weight and gestational age at delivery. RESULTS: Higher incidence of
      vaginal delivery among subjects with high value of hardiness in relation with
      subjects with low value of hardiness has been found. The index parameter which
      seems most conditioning the ability to affront the stress of labor is the
      "Challenge". Significant correlation between the value of hardiness and other
      parameters of delivery are not evident. CONCLUSIONS: The values of the Hardiness
      test seems to be significant, but it would be a mistake to use them as a
      predictive index of the modality of delivery; it seems to be most important to
      employ the test to assure more care to pregnant women with a reduction of the
      ability to face the stress of labor and delivery, in order to reduce the risk of
      problems in mother-child relations.

PMID- 10069167
TI  - [Immune tolerance in pregnancy. Maternal-fetal interactions].
AB  - The conceptus may be considered as a sort of semi-allogenic graft for the
      maternal organism, since it shares a half of genomic complement with the father.
      Nevertheless, its rejection does not take place physiologically during a
      pregnancy. The mechanisms resulting in the maternal immune tolerance versus the
      conceptus are not yet completely clarified. Such mechanisms are probably multiple
      and interacting with each other. In animal and in vitro studies provide evidence
      suggesting that the following factors are important in producing the maternal
      immune tolerance: the anatomical position of the fetus; the absence of expression
      of the class I and II Major Histocompatibility Complex (MHC) molecules in
      trophoblast tissues; the activity of blocking antibodies; a modification of the
      immune response; the fetal-placental production of immunosuppressive hormones and
      substances. Amongst pregnancy-related changes in the immune response, a reduced
      Natural Killer (NK) cell activity and an increased synthesis of Th2 cytokines
      (which inhibit the cell-mediated immunity) with an altered Th1/Th2 balance appear
      to be remarkably important. With regard to fetal-placental hormones, progesterone
      seems to exert an important immunosuppressive influence mediated by the protein
      named "Progesterone Induced Blocking Factor" (PIBF). Nevertheless, the real
      contribution of each of the above mentioned mechanisms still remains to be
      elucidated in humans.

PMID- 10069168
TI  - [Contraception after heart transplantation].
AB  - It was observed that fertility and menstrual function in heart-transplanted
      women, impaired before the operation, become normal with a new heart. The
      restoration of reproductive function is also confirmed by many cases of pregnancy
      in heart-transplant recipients, reported in the literature. Twenty-four cases
      were published worldwide up to 1997, out of which eighteen had a positive result.
      Also a case personally treated was successful. The outcome of a pregnancy after
      heart transplantation is, then, generally positive. Nevertheless, such a
      pregnancy involves important maternal and fetal risks. Thus, the gynecologist has
      to provide correct information about both such risks and the most suitable
      contraceptive methods, for these patients. Oral contraceptives are very effective
      and, in the new low-dose formulations, free from serious adverse effects. No
      adverse effects have been observed in our patient, who represents the only case,
      reported in the literature, in which an estroprogestinic contraception was
      utilized before a pregnancy. In conclusion, during an oral contraception or after
      a tubal sterilization, pregnancy is really unlikely to occur. Thus, when the
      couple either has completed the familial nucleus or does not desire offspring, a
      doubt is at least justified as to whether these safer methods of contraception
      are advisable in such women.

PMID- 10069169
TI  - [A case of Leydig cell virilizing tumor of the ovary].
AB  - A case of Leydig cell virilizing tumor of the ovary in a 68 year old woman, with
      clinical signs of virilization, clitoromegaly and androgenic alopecia is
      described. An RMN of encephalon and an abdominal ultrasound were normal.
      Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the
      patient had regression of hirsutism, and plasma testosterone dropped to normal
      level.

PMID- 10069170
TI  - [Craniosynostosis: is prenatal diagnosis possible?].
AB  - The authors report a case which demonstrates how an interdisciplinary
      collaboration between the obstetrician and pediatrician may be activated in the
      event of a suspected fetal malformation, in this case craniosynostosis, although
      it is important to recognise the diagnostic limitations of ultrasonography
      regarding this type of pathology.

PMID- 10069171
TI  - [Estrogen and progestin treatment in postmenopause. Effects on the endometrium].
AB  - BACKGROUND AND AIMS: It has been well demonstrated that menopausal disorders
      resulting from the lack of estrogens may be delayed and partly eliminated by
      appropriate hormone replacement therapy. The aim of this study was to demonstrate
      the absolute innocuity of the association of estrogen and progestin. METHODS: The
      authors used an association of conjugated equine estrogens and medroxi
      progesterone acetate to treat menopausal syndrome in 80 women aged between 48 and
      55 years old. The study lasted 2 years. RESULTS AND CONCLUSIONS: The results
      obtained showed the good tolerability and marked efficacy of the drugs used, as
      well as the absolute innocuity in relation to the target organs, namely the
      breast and endometrium. No cases of endometrial hyperplasia with atypical
      development or malignant evolution were reported during the study and there was a
      significant improvement in lipid metabolism, vasomotor or psychomotive disorders,
      as well as increased trophism of the genitourinary tract and skeleton.

PMID- 10069172
TI  - Glomerulonephritis in mixed cryoglobulinaemia: what treatment?

PMID- 10069173
TI  - The relative roles of circulating and tissue renin-angiotensin systems.

PMID- 10069174
TI  - Cardiovascular and renal risks of calcium-channel blockers--news from the HOT
      study.

PMID- 10069175
TI  - The clinical diagnosis of hypertensive nephrosclerosis--how reliable is it?

PMID- 10069176
TI  - Clostridium difficile and antibiotic-associated diarrhoea--importance of C.
      difficile for the nephrologist.

PMID- 10069177
TI  - Anaemia in the patient with renal insufficiency: documenting the impact and
      reviewing treatment strategies.
AB  - This paper attempts to present a context in which nephrologists can re-evaluate
      definitions of acceptable haemoglobin levels in renal populations, and re-examine
      previous notions about the impact of relative and absolute anaemia on patients
      with progressive renal insufficiency. Also, the nephrology community needs to
      examine rigorously treatment strategies aimed at reversing anaemia specifically
      in this population. Data are presented to support the notion that anaemia is
      disadvantageous to the patients with progressive renal insufficiency, and does
      need to be treated. The ongoing poor prognosis of patients receiving renal
      replacement therapy may well be due to our previous inattention to this
      correctable cause of morbidity early in the course of progressive renal disease.
      Long-term studies addressing these important clinical issues need to be
      supported, and evaluated within both immediate and future economic implications.

PMID- 10069178
TI  - Familial aggregation of end-stage renal failure: aetiological implications.

PMID- 10069179
TI  - Vascular steal syndrome and ischaemic monomelic neuropathy: two variants of upper
      limb ischaemia after haemodialysis vascular access surgery.

PMID- 10069180
TI  - Transplantation strategies in type 1 primary hyperoxaluria: the issue of
      pyridoxine responsiveness.

PMID- 10069181
TI  - Nephrotoxicity of increased glomerular protein traffic.

PMID- 10069182
TI  - Laparoscopy and retroperitoneoscopy--novel techniques of which clinical
      nephrologists should be aware.

PMID- 10069183
TI  - Discontinuing dialysis: patient's wishes and professional judgement.

PMID- 10069184
TI  - Costimulatory molecules as targets for the induction of transplantation
      tolerance.

PMID- 10069185
TI  - X-linked hypophosphataemia: a homologous disorder in humans and mice.
AB  - X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis
      characterized by growth retardation, rickets and osteomalacia, hypophosphataemia,
      and aberrant renal Pi reabsorption and vitamin D metabolism. Studies in murine
      Hyp and Gy homologues have identified a specific defect in Na+-Pi cotransport at
      the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D3
      (1,25(OH)2D) synthesis and degradation, and an intrinsic defect in bone
      mineralization. The mutant gene has been identified in XLH patients, by
      positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to
      signify a PHosphate-regulating gene with homology to Endopeptidases on the X
      chromosome. PHEX/Phex is expressed in bones and teeth but not in kidney and
      efforts are under way to elucidate how loss of PHEX/Phex function elicits the
      mutant phenotype. Based on its homology to endopeptidases, it is postulated that
      PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s)
      which plays a key role in the regulation of bone mineralization, renal Pi
      handling and vitamin D metabolism.

PMID- 10069186
TI  - Comparative cytotoxicity of ionic and non-ionic radiocontrast agents on MDCK cell
      monolayers in vitro.
AB  - BACKGROUND: Intravascular radiocontrast agents may cause acute renal failure,
      particularly in patients with pre-existing renal insufficiency. Direct cytotoxic
      effects of radiocontrast agents on renal tubular cells may contribute to the
      pathogenesis of radiocontrast-induced nephropathy. METHODS: We analysed the
      cytotoxicity of the ionic radiocontrast agents diatrizoate (monomeric) and
      ioxaglate (dimeric), as well as of the non-ionic radiocontrast agents iohexol
      (monomeric) and iodixanol (dimeric) on the renal epithelial Madin Darby Canine
      Kidney (MDCK) cell line grown on permeable supports. The toxicity assays assessed
      cell viability, transmonolayer resistance and inulin permeability between the
      apical and basal cell culture compartment. In addition, the distribution of the
      tight-junction-associated membrane proteins ZO-1 and occludin was analysed using
      immunofluorescence microscopy. RESULTS: In all assays the high osmolal ionic
      compound diatrizoate had significant cytotoxic effects that included the partial
      redistribution of the tight-junction-associated membrane proteins into a
      cytoplasmic compartment. To a lesser extent this redistribution also occurred
      with the dimeric ionic compound ioxaglate, but not with the non-ionic
      radiocontrast agents. With regards to cell viability, transmonolayer resistance
      and inulin permeability the radiocontrast agents with reduced osmolality were
      significantly less toxic than diatrizoate, independent of their ionic strength.
      CONCLUSIONS: Physicochemical factors contribute to the cytotoxicity of
      radiocontrast agents in vitro. The redistribution of tight-junction-associated
      membrane proteins by the ionic radiocontrast agents corresponds with the loss of
      the barrier function of the epithelial cell monolayer, which is a major
      pathophysiological mechanism in acute renal failure. The radiocontrast agents
      with reduced osmolality are less cytotoxic than diatrizoate, independent of their
      ionicity. Hyperosmolality appears to be a more important determinant of the
      cytotoxicity of diatrizoate than ionic strength.

PMID- 10069187
TI  - Neovascularization at the vascular pole region in diabetic glomerulopathy.
AB  - BACKGROUND: Diabetic nephropathy is associated with renal structural changes
      involving all of the compartments. Most characteristic is the diabetic
      glomerulopathy. Studies of the histological changes during the early phases of
      nephropathy have included the glomerulopathy and also the juxtaglomerular
      structures. Neovascularization, well-known in diabetic retinopathy, has also been
      observed in the kidney. The present study concerns estimates of frequency of
      neovascularization at the vascular pole region in early stages of diabetic
      nephropathy. METHODS: Extra efferent arterioles at the glomerular vascular pole
      were detected during measurements of the vascular pole area applying 1-microm
      serial sections through kidney biopsies. It was observed that more than one
      efferent arteriole existed occasionally. The present study was carried out with
      the aim of estimating the frequency of this phenomenon in diabetic patients and
      in non-diabetic controls, the diabetic patients categorized according to the
      level of albumin excretion rate. RESULTS: Neovascularization was first observed
      in IDDM patients with microalbuminuria. Some of the cases presented the
      phenomenon in all of the glomeruli studied. As the examinations of many kidney
      biopsies continued the phenomenon was observed also in the non-diabetic control
      group and in one IDDM patient with normoalbuminuria. However, the frequency was
      statistically highly significantly increased in patients with elevated albumin
      excretion. Within this group a strong correlation between frequency of
      neovascularization and the severity of diabetic glomerulopathy is seen.
      CONCLUSIONS: The vascular abnormality localized to the vascular pole region is
      observed occasionally in the normal kidney, but the frequency is increased in
      patients with diabetic glomerulopathy. The abnormality may develop as a
      consequence of a long-standing diabetic glomerulopathy and might lead to less
      pronounced elevation of albumin excretion.

PMID- 10069188
TI  - Decreased IgA1 response after primary oral immunization with live typhoid vaccine
      in primary IgA nephropathy.
AB  - INTRODUCTION: Patients with primary IgA nephropathy (IgAN) have an increased
      level of immunological memory to certain parenteral recall antigens. We recently
      found a deficient IgA1 immune response after intranasal challenge with a neo
      antigen: cholera toxin subunit B. In the present study, we assessed the specific
      IgA1 and IgA2 antibody response in plasma, peripheral blood cells and mucosal
      secretions after primary enteral immunization. METHODS: Twenty eight IgAN
      patients, 26 patients with non-immunological renal disease and 32 healthy
      subjects were immunized orally with three sequential doses of live, attenuated,
      Salmonella typhi Ty21a. The humoral immune response in body fluids and antibody
      synthesis by circulating B cells was assessed in specific ELISAs and ELIPSAs
      respectively. RESULTS: Oral immunization resulted in significantly (P<0.0001)
      increased IgM, IgG, IgA, IgA1 and IgA2 responses in all groups, both in plasma
      and in circulating B cells in vitro. The IgA1 response in plasma was
      significantly (P<0.05) lower in IgAN patients, while no significant differences
      in IgM (P=0.36), IgG (P= 0.79) or IgA2 (P=0.45) responses were found as compared
      with matched control groups. The amount of IgA1 synthesized by circulating B
      cells tended to be lower in IgAN patients. No significant IgA response after oral
      immunization with S. typhi Ty21a was found in saliva (P=0.11) or tears (P=0.10).
      CONCLUSIONS: These data suggest an IgA1 hyporesponsiveness in patients with IgAN
      that is not only apparent after primary challenge of the nasal-associated
      lymphoid tissue but also after presentation to the gut. Previous results after
      parenteral recall immunization may be explained by assuming that IgAN patients
      require more frequent and/or longer exposure to IgA1-inducing antigens on their
      mucosal surfaces before they reach protective mucosal immunity. As a consequence,
      overproduction of IgA1 antibodies occurs in the systemic compartment, accompanied
      by an increased number of IgA1 memory cells.

PMID- 10069189
TI  - Increased renal resistive index in patients with essential hypertension: a marker
      of target organ damage.
AB  - BACKGROUND: Increased renal resistance detected by ultrasound (US) Doppler has
      been reported in severe essential hypertension (EH) and recently was shown to
      correlate with the degree of renal impairment in hypertensive patients with
      chronic renal failure. However, the pathophysiological significance of this
      finding is still controversial. METHODS: In a group of 211 untreated patients
      with EH, we evaluated renal resistive index (RI) by US Doppler of interlobar
      arteries and early signs of target organ damage (TOD). Albuminuria was measured
      as the albumin to creatinine ratio (ACR) in three non-consecutive first morning
      urine samples. Left ventricular mass was evaluated by M-B mode echocardiography,
      and carotid wall thickness (IMT) by high resolution US scan. RESULTS: RI was
      positively correlated with age (r=0.25, P=0.003) and systolic blood pressure
      (SBP) (r=0.2, P=0.02) and with signs of early TOD, namely ACR (r=0.22, P=0.01)
      and IMT (r=0.17, P<0.05), and inversely correlated with renal volume (r=-0.22,
      P=0.01) and diastolic blood pressure (r=-0.23, P=0.006). Multiple linear
      regression analysis demonstrated that age, gender, ACR and SBP independently
      influence RI and together account for approximately 20% of its variations
      (F=8.153, P<0.0001). When clinical data were analysed according to the degree of
      RI, the patients in the top quartile were found to be older (P<0.05) and with
      higher SBP (P<0.05) as well as early signs of TOD, namely increased ACR (P<0.002)
      and IMT (P<0.005 by ANOVA), despite similar body mass index, uric acid, fasting
      blood glucose, lipid profile and duration of hypertension. Furthermore, patients
      with higher RI showed a significantly higher prevalence of microalbuminuria (13
      vs 12 vs 3 vs 33% chi2=11.72, P=0.008) and left ventricular hypertrophy (40 vs 43
      vs 32 vs 60%, chi2=9.25, P<0.05). CONCLUSIONS: Increased RI is associated with
      early signs of TOD in EH and could be a marker of intrarenal atherosclerosis.

PMID- 10069190
TI  - Hyperhomocyst(e)inaemia in children with chronic renal failure.
AB  - BACKGROUND: Hyperhomocyst(e)inaemia has been identified as a significant risk
      factor for the occurrence of atherosclerosis in adults with chronic renal
      failure. Because of its presumed direct toxic effect on the vascular wall, long
      standing hyperhomocyst(e)inaemia in children with chronic renal failure might
      have an important influence on their risk of future development of
      atherosclerosis. Hitherto no data on hyperhomocyst(e)inaemia in children with
      renal failure have been published. METHODS: We investigated 16 children with
      chronic renal failure on conservative management, 12 children on haemodialysis
      and 17 children with a renal transplant. Age-matched controls were used for
      comparison. Plasma homocyst(e)ine levels after an overnight fast were determined
      by HPLC. Glomerular filtration rate was estimated by the Schwartz formula.
      RESULTS: Mean plasma homocyst(e)ine levels were 12.6 +/- 5.2 micromol/l in the
      conservatively managed group, 22.2 +/- 13.5 micromol/l in the haemodialysed
      group, 14.2 +/- 2.1 micromol/l in transplanted children with an estimated GFR >
      60 ml/min/1.73 m2 and 17.5 +/- 5.1 micromol/l in transplanted children with a
      lower estimated GFR. In all groups homocyst(e)ine levels were significantly
      elevated as compared to controls. Homocyst(e)ine levels were significantly
      correlated with age and negatively correlated with estimated GFR and serum folate
      levels. CONCLUSIONS: Hyperhomocyst(e)inaemia is a feature of chronic renal
      failure in children as well as in adults. Elevated homocyst(e)ine levels can
      already be demonstrated in children with renal failure before end-stage renal
      disease has developed and persist after renal transplantation. Whether treatment
      of hyperhomocyst(e)inaemia in children with renal failure decreases the risk for
      future atherosclerosis remains to be proven.

PMID- 10069191
TI  - Fluid state and blood pressure control in patients treated with long and short
      haemodialysis.
AB  - BACKGROUND: Patients treated at the haemodialysis (HD) centre in Tassin, France
      have been reported to have superior survival and blood pressure (BP) control.
      This control has been ascribed to maintenance of an adequate fluid state,
      antihypertensive drugs being required in < 5% of the patients, although it could
      not be excluded that a high dose of HD regarding removal of uraemic toxins might
      also have been of value. METHODS: The aim of the study was to assess the fluid
      state and BP in normotensive patients on long HD (8 h) in Tassin (group TN) using
      bioimpedance to measure extracellular volume (ECV), ultrasound for determining
      the inferior vena cava diameter (IVCD), and 'on-line' monitoring of the change in
      blood volume (BV), and to compare them with normotensive (group SN) and
      hypertensive (group SH) patients on short HD (3-5 h) at centres in Sweden. ECV
      was normalized (ECVn) by arbitrarily setting the median ECV (in % of body weight)
      in SN patients at 100% for each gender, recalculating the individual values and
      combining the results for male and female patients in each group. RESULTS: The
      dose of HD (Kt/V urea) was higher for TN patients than for Swedish patients who
      had a similar Kt/V, whether hypertensive or not. SH patients had significantly
      higher ECVn and IVCD than TN and SN patients. TN and SN patients did not differ
      significantly regarding ECVn and IVCD before and after HD. However, in a subgroup
      of eight TN patients, ECVn was below the range of that in SH and SN patients, due
      to obesity with a high body mass index. Another subgroup of 14 TN patients had a
      higher ECVn than most of the SN patients and also higher than the median ECVn in
      the SH group, without any difference in body mass index, but they were
      nevertheless normotensive. The fall in BV was greater in SN than in TN patients,
      presumably due to a higher ultrafiltration rate in SN patients. However, SH
      patients had a smaller change in BV than SN patients, presumably because their
      state of overhydration facilitated refilling of BV from the interstitial fluid.
      CONCLUSIONS: Normotension can be achieved independently of the duration and dose
      (Kt/V urea) of HD, if the control of post-dialysis ECV is adequate. However, this
      is more difficult to achieve with short than with more prolonged HD during which
      the ultrafiltration rate is lower, BV changes are smaller and intradialysis
      symptoms less frequent. The results in the subgroup of patients with high ECVn at
      Tassin suggest that normotension may also be achieved in patients with fluid
      overload provided that the dialysis time is long enough to ensure more efficient
      removal of one or more vasoactive factors that cause or contribute to
      hypertension.

PMID- 10069192
TI  - Validation of haemodialysis recirculation and access blood flow measured by
      thermodilution.
AB  - BACKGROUND: Recirculation (R) and access blood flow (Qac) measurements are
      considered useful indicators of adequate delivery of haemodialysis. It was the
      purpose of this study to compare measurements of R and Qac obtained by two
      different techniques which are based on the same principle of indicator dilution,
      but which differ because of the characteristics of the injection and detection of
      the different indicators used. METHODS: Recirculation measured by a thermal
      dilution technique using temperature sensors (BTM, Fresenius Medical Care) was
      compared with recirculation measured by a validated saline dilution technique
      using ultrasonic transducers placed on arterial and venous segments of the
      extracorporeal circulation (HDM, Transonic Systems, Inc.). Calculated access
      flows were compared by Bland Altman analysis. Data are given as mean +/- SD.
      RESULTS: A total of 104 measurements obtained in 52 treatments (17 patients, 18
      accesses) were compared. Recirculation measured with correct placement of blood
      lines and corrected for the effect of cardiopulmonary recirculation using the
      'double recirculation technique' was -0.02 +/- 0.14% by the BTM technique and not
      different from the 0% measured by the HDM technique. Recirculation measured with
      reversed placement of blood lines and corrected for the effect of cardiopulmonary
      recirculation was 19.66 +/- 10.77% measured by the BTM technique compared with
      20.87 +/- 11.64% measured by the HDM technique. The difference between techniques
      was small (-1.21 +/- 2.44%) albeit significant. Access flow calculated from BTM
      recirculation was 1328 +/- 627 ml/min compared with 1390 +/- 657 ml/min
      calculated by the HDM technique. There was no bias between techniques.
      CONCLUSION: BTM thermodilution yields results which are consistent with the HDM
      ultrasound dilution technique with regard to both recirculation and access flow
      measurement.

PMID- 10069193
TI  - Renal effects of amlodipine in normotensive renal transplant recipients.
AB  - Renal effects of amlodipine in normotensive renal transplant recipients. The use
      of cyclosporin A (CsA) has improved the success of renal transplantation, but is
      associated with hypertension and significant renal toxicity. Previous reports
      suggest that calcium channel blockers may be useful in opposing the adverse
      effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for
      8 weeks) on renal function in 27 normotensive renal transplant recipients with
      stable renal function, in a double-blind, placebo-controlled, multicentre, cross
      over study. Amlodipine significantly reduced serum creatinine concentration
      relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and
      there was a strong trend towards an increase in effective renal plasma flow on
      amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular
      filtration rate and lithium clearance were unaffected. Trough CsA blood
      concentration was unaffected. Amlodipine was well tolerated, with a low incidence
      of adverse events, and did not affect blood pressure or heart rate. In
      conclusion, amlodipine reduced serum creatinine in normotensive renal transplant
      recipients after only 8 weeks treatment, and was well tolerated in concomitant
      administration with CsA.

PMID- 10069194
TI  - Immediate and early renal function after living donor transplantation.
AB  - BACKGROUND: In order to assess the immediate renal function after living donor
      transplantation, renal function was compared in eight renal allograft recipients
      and their living related kidney donors during the first 24 h after
      transplantation. METHODS: Substantial and comparable intraoperative volume
      loading with Ringer's acetate and mannitol was performed together with the
      administration of frusemide. Glomerular filtration rate (GFR) and effective renal
      plasma flow (ERPF) were estimated by the clearances of inulin and p
      aminohippurane, respectively. Tubular reabsorptive function and injury were
      estimated from the clearance of lithium, the fractional excretion of sodium and
      the urinary excretion of N-acetyl-beta-glucosaminidase. RESULTS: One hour after
      completion of surgery, GFR (54 +/- 7 ml/min) and ERPF (294 +/- 35 ml/min) were
      only 30% lower in the grafts than in the remaining donor kidneys, increasing to
      similar levels within 3 h. Only minor tubular dysfunction and injury were
      revealed in the grafted kidneys, and these tended to normalize within 24 h.
      CONCLUSIONS: By the present transplantation procedure comprising short ischaemia
      time and substantial volume expansion combined with mannitol and frusemide
      administration, kidneys from living donors regain nearly normal function within a
      few hours after transplantation.

PMID- 10069195
TI  - Reduced kidney transplant rejection rate and pharmacoeconomic advantage of
      mycophenolate mofetil.
AB  - BACKGROUND: Several multinational controlled clinical trials have shown that
      triple therapy immunosuppressive regimens which include mycophenolate mofetil
      (MMF), cyclosporin A (CSA) and steroids (S) are superior compared with
      conventional regimens which include azathioprine (AZA), CSA and S, mainly because
      MMF reduces the rate of acute rejection episodes in the first 6 months after
      kidney transplantation. Post-marketing studies are useful to evaluate the general
      applicability and costs of MMF-based immunosuppressive regimens. METHODS: Based
      on the excellent results of the published controlled clinical trials, we have
      changed the standard triple therapy immunosuppressive protocol (AZA+CSA+S) to an
      MMF-based regimen (MMF+CSA+S) at our centre. To analyse the impact of this change
      in regimen, we have monitored 6-month patient and graft survival, rejection rate,
      serum creatinine and CSA levels, as well as the costs of the immunosuppressive
      and anti-rejection treatments, in 40 consecutive renal transplant recipients (MMF
      group) and have compared the data with 40 consecutive patients transplanted
      immediately prior to the change in regimen (AZA group). RESULTS: Recipient and
      donor characteristics were similar in the AZA and MMF groups. Patient survival
      (37/40; 92.5% in the AZA group vs 38/40; 95% in the MMF group), graft survival
      (36/40 vs 36/40; both 90%) and serum creatinine (137+/-56 vs 139+/-44 micromol/l)
      after 6 months were not significantly different. However, the rate of acute
      rejection episodes (defined as a rise in creatinine without other obvious cause
      and treated at least with pulse steroids) was significantly reduced with MMF from
      60 to 20% (P=0.0005). The resulting cost for rejection treatment was lowered 8
      fold (from sFr. 2113 to 259 averaged per patient) and the number of transplant
      biopsies was lowered > 3-fold in the MMF group. The cost for the
      immunosuppressive therapy was increased 1.5-fold with MMF (from sFr. 5906 to 9231
      per patient for the first 6 months). CONCLUSIONS: The change from AZA to MMF
      resulted in a significant reduction in early rejection episodes, resulting in
      fewer diagnostic procedures and rehospitalizations. The optimal long-term regimen
      in terms of patient and pharmacoeconomic benefits remains to be defined.

PMID- 10069196
TI  - Leptin in CAPD patients: serum concentrations and peritoneal loss.
AB  - BACKGROUND: To determine whether serum leptin concentrations in patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD) are influenced by
      peritoneal loss of leptin and to compare serum leptin levels of normal subjects
      with those of patients receiving renal replacement therapy such as haemodialysis
      (HD), CAPD, or kidney transplantation. SUBJECTS AND METHODS: Eighty-four
      individuals were investigated: six females and 14 males on standard CAPD; 13
      females and 13 males on chronic HD; 10 female and eight male kidney transplant
      recipients, and 10 female and 10 male subjects as controls. Morning serum, 8-h
      and 24-h samples of peritoneal fluid concentrated to 6-20-fold by Centricon 3
      (cutoff 3000 daltons), and 24-h urinary concentrations of leptin were measured
      with commercial RIA (Linco Research, Inc., USA). Venous blood and peritoneal
      fluid samples of albumin, beta2-microglobulin, glucose, urea, and creatinine were
      determined by standard laboratory techniques. Serum insulin levels were measured
      by radioimmunoassay. RESULTS: Patients (men and women) on CAPD and after kidney
      transplantation exhibited significantly higher serum concentrations of leptin and
      leptin/BMI ratios than control subjects. These increased values did not reach
      statistical significance in HD patients. Serum leptin concentrations were
      correlated very significantly with BMI in all cases (r=0.380, P<0.001). Moreover,
      in CAPD patients (r=0.630, P<0.007) and in HD patients (r=0.668, P<0.005), but
      not in kidney transplant recipients or control subjects, significant correlations
      were observed between serum leptin and insulin concentrations. Residual renal
      function (RRF) in the range 0-12.8 ml/min and serum beta2-microglobulin levels in
      the range 7.9-47.1 mg/l did not influence serum leptin levels in CAPD and HD
      patients. As expected, leptin was detected in the peritoneal fluid of CAPD
      patients. Twenty-four-hour peritoneal loss (30.95+/-21.05 ng/min) and 24-h
      peritoneal clearance (0.01+/-0.01 ml/kg/min) of leptin account for only 3.9% of
      estimated whole-body leptin production rate and 0.7% of leptin clearance from
      plasma respectively. Twenty-four-hour urinary losses of leptin in CAPD patients
      were negligible, accounting for 5.6+/-1.8% (range 0.3-15.2%) of total (peritoneal
      and urinary) loss of this hormone. CONCLUSIONS: These findings suggest that serum
      leptin levels are not affected by continuous peritoneal loss of leptin during
      CAPD and that insulin resistance and hyperinsulinaemia contribute to elevated
      serum leptin concentrations in CAPD and HD patients. The aetiology of increased
      serum leptin levels in kidney transplant recipients is probably different from
      that in dialysis patients.

PMID- 10069197
TI  - High prevalence of hepatitis G virus (HGV) infections in dialysis staff.
AB  - BACKGROUND: Patients on renal replacement therapy, haemodialysis (HD), or after
      kidney transplantation (TX), are known to be at risk of acquiring blood-borne
      infections (HBV, HCV). GBV-C/Hepatitis G virus (HGV) has been described recently
      and is considered to cause blood-borne infections. The aim of this study was to
      analyse the risk for the medical staff of HD and TX patients to acquire HGV
      infection. METHODS: Eighty-five HD patients and 86 TX recipients were compared
      with 49 health-care workers and 64 blood donors as controls. The HGV prevalence
      was determined by RT-PCR and antibodies to E2 protein. RESULTS: A high prevalence
      of HGV was found in the medical staff (24%) which nearly corresponded to the
      prevalence of the patients (TX 36%, HD 25%) but not to the controls (9%). In
      contrast, the prevalence of HCV was low in the medical staff (2%) and controls
      (0%) but high in HD (13%) and TX (13%). Age and duration of employment in the
      department did not significantly influence the HGV prevalence in staff. The
      number of viraemic subjects in staff was high, possibly indicating a more recent
      infection. CONCLUSION: An occupational risk for HGV exists in medical staff of
      dialysis and transplant patients. Further routes of transmission than only
      parenteral may play a role in this setting.

PMID- 10069198
TI  - How can videolaparoscopy be used in a peritoneal dialysis programme?
AB  - BACKGROUND: Recently videolaparoscopy is considered to have a vaster use in
      surgery due to the undeniable benefits such as low operatory traumatism, quick
      recovery of canalization, a short stay in the hospital and minor scarring.
      METHODS: Forty patients were treated with peritoneal dialysis (PD); 15
      videolaparoscopic procedures were performed on 13 patients before starting PD and
      two during the course of PD. The videolaparoscopy procedure was started by
      inducing pneumoperitoneum after initiation of general anaesthesia through
      endotracheal intubation. RESULTS: Peritoneal catheter placement was carried out
      in 11 ESRD patients showing abdominal scars due to previous laparotomies; their
      abdominal condition precluded safe PC placement using conventional non
      laparoscopic procedures with local anaesthesia. Release of adhesions was
      performed only in two patients. Videolaparoscopy was also used in three patients
      for elective cholecystectomy; 2/3 underwent concomitant PC insertion. One patient
      was submitted to cholecystectomy during the course of CAPD; following the
      procedure we left the peritoneum dry overnight and then we started temporary IPD,
      using small volumes, avoiding haemodialysis (HD). Regular CAPD was resumed 6 days
      later. Finally, videolaparoscopy was also used for diagnostic purpose i.e. in one
      59-year-old man patient who had a peritoneal catheter obstruction. Repeated
      rescue attempts using urokinase solution to irrigate the peritoneal catheter had
      been used in vain attempts prior to the procedure. CONCLUSIONS: Videolaparoscopy
      proves to be a useful tool in a PD programme. Firstly, it may be used as a
      technique for catheter implantation, not as a routine procedure but in patients
      with extensive abdominal scars due to previous laparotomy, i.e. at risk for
      accidental viscera perforation due to the possibility of adhesions between
      intestinal loops and parietal peritoneum. Secondly, videolaparoscopy used for
      abdominal surgery allows the resumption of PD immediately after surgical
      procedure and thus avoiding HD. Videolaparoscopy is fundamental for diagnosis and
      rescue of catheter dysfunction and has an integral role in the successful
      management of these patients in extending catheter function and permitting safe
      replacement of peritoneal catheter if it becomes necessary. Along with the
      undeniable advantages, remains the disadvantages that it must be carried out by
      an expert surgeon in an operating theatre while the patient is under general
      anaesthesia.

PMID- 10069199
TI  - The use of treatment modality specific analysis according to Selwood in
      epidemiological studies.

PMID- 10069200
TI  - Membranous nephropathy associated with hepatitis B virus infection: long-term
      clinical and histological outcome.

PMID- 10069201
TI  - Crow-Fukase syndrome--immunoadsorption plasmapheresis effectively lowers elevated
      interleukin-6 concentration.

PMID- 10069202
TI  - Hyponatraemia as the presenting feature of isolated thyrotropin deficiency.

PMID- 10069203
TI  - Diabetes insipidus as the presenting symptom of Wegener's granulomatosis.

PMID- 10069204
TI  - Vasculitis look-alikes: variants of renal atheroembolic disease.

PMID- 10069205
TI  - Severe renal arterio-arteriolosclerosis after cocaine use.

PMID- 10069206
TI  - Thrombotic microangiopathy related to anticardiolipin antibody in a renal
      allograft.

PMID- 10069207
TI  - Haemolytic-uraemic syndrome in an adult male with Aeromonas hydrophila
      enterocolitis.

PMID- 10069208
TI  - Parenteral copper sulfate poisoning causing acute renal failure.

PMID- 10069209
TI  - Haemodialysis access graft with shunting through an iatrogenic fistula--the
      diagnostic role of magnetic resonance flow measurement.

PMID- 10069210
TI  - Lymph leakage following subclavian vein catheterization.

PMID- 10069211
TI  - Parathyroid carcinoma with multiple lung metastases.

PMID- 10069212
TI  - Daytime hypertension, sleep apnea and metabolic alkalosis in a haemodialysis
      patient--the result of sodium bicarbonate abuse.

PMID- 10069213
TI  - The haemodialysis patient who developed acute respiratory distress syndrome after
      a trip to a hot spring spa.

PMID- 10069214
TI  - Haemodialysis for severe hyperammonaemic coma complicating urinary diversions.

PMID- 10069215
TI  - Progressive multifocal leukoencephalopathy in a renal transplant patient
      diagnosed by JCV-specific DNA amplification and an intrathecal humoral immune
      response to recombinant virus protein 1.

PMID- 10069216
TI  - Complete regression of a major hyperprolactinaemia after renal transplantation.

PMID- 10069217
TI  - Concomitant parvovirus B19 and cytomegalovirus infections after living-related
      renal transplantation.

PMID- 10069218
TI  - Late renal transplant arterial thrombosis in a patient with systemic lupus
      erythematosus and antiphospholipid syndrome.

PMID- 10069219
TI  - Familial Mediterranean fever--renal involvement by diseases other than amyloid.
AB  - BACKGROUND: In patients with familial Mediterranean fever (FMF) renal involvement
      is usually in the form of AA amyloidosis. There is increasing evidence that renal
      involvement may be due to diseases other than amyloid as well. METHODS: Amongst
      302 children with FMF we observed and followed 28 with typical clinical and
      laboratory features of vasculitis. The diagnosis of FMF was established according
      to the Tel Hashomer criteria. RESULTS: Polyarteritis nodosa, protracted febrile
      attacks and Henoch-Schonlein purpura were diagnosed in 4, 13, and 11 patients,
      respectively. The presentation was often difficult to distinguish from FMF
      attacks, but protracted febrile attacks lasting several weeks, hypertension,
      thrombocytosis, and dramatic responses to corticosteroid therapy that were
      observed in many cases were different from what is observed in classical FMF.
      CONCLUSIONS: We suggest that FMF, perhaps as a consequence of impaired control of
      inflammatory responses, predisposes to vasculitis with renal involvement.

PMID- 10069220
TI  - Hyperkalaemic muscle paresis--side-effect of prostaglandin inhibition in a
      haemodialysis patient.

PMID- 10069221
TI  - Back pain and Staphylococcal bacteraemia in haemodialysed patients--beware!

PMID- 10069222
TI  - A desperate case of failing vascular access--management of superior vena cava
      thrombosis, recurrent bacteraemia, and acute clavicular osteomyelitis.

PMID- 10069223
TI  - A malignant 'incidentaloma' in a patient with autosomal dominant polycystic
      kidney disease.

PMID- 10069224
TI  - Nodular glomerulosclerosis in a renal allograft of a non-diabetic recipient.

PMID- 10069225
TI  - Radiological view of sclerosing peritonitis.

PMID- 10069226
TI  - 'The vanished occiput'.

PMID- 10069227
TI  - Management of acute myeloid leukaemia following myelodysplastic syndrome in a
      kidney graft recipient.

PMID- 10069228
TI  - The first percutaneous renal biopsies in Italy.

PMID- 10069229
TI  - Laudatio. Professor Maria Ratner.

PMID- 10069231
TI  - Definition of 'focal segmental glomerulosclerosis'.

PMID- 10069232
TI  - Gitelman syndrome and chondrocalcinosis.

PMID- 10069233
TI  - Ceruloplasmin in small vessel vasculitis.

PMID- 10069234
TI  - Does uraemia potentiate bacteraemia-associated haemolysis in patients receiving
      erythropoietin?

PMID- 10069235
TI  - Changes in adrenomedullin plasma concentrations during haemodialysis in patients
      with chronic renal failure.

PMID- 10069236
TI  - Atheroembolic disease associated with the use of low-molecular-weight heparin
      during haemodialysis.

PMID- 10069237
TI  - An exploratory study examining the influence of religion on attitudes towards
      organ donation among the Asian population in Luton, UK.

PMID- 10069238
TI  - Marked elevation of blood cyclosporin and tacrolimus levels due to concurrent
      metronidazole therapy.

PMID- 10069239
TI  - Omeprazole-induced agranulocytosis in a kidney transplant recipient.

PMID- 10069240
TI  - How inconsistencies in racial classification demystify the race construct in
      public health statistics.

PMID- 10069241
TI  - Pesticides and reproduction.

PMID- 10069242
TI  - Raising response rates: getting to yes.

PMID- 10069243
TI  - Why race is differentially classified on U.S. birth and infant death
      certificates: an examination of two hypotheses.
AB  - Among U.S. infants who die within a year of birth, classification of race on
      birth and death certificates may differ. I investigate two hypotheses: (1) The
      race of infants of different-race parents is more likely to be differentially
      classified at birth and death than the race of infants of same-race parents. (2)
      States with a greater proportion of infant deaths of a given race are less likely
      to differentially classify infants of that race on birth and death certificates
      than states with a smaller proportion of infant deaths of that race. Using the
      Linked Birth/Infant Death data tape for 1983-1985, I assessed the first
      hypothesis by comparing rates of differential classification for infants with
      different-race parents and same-race parents. To assess the second hypothesis, I
      examined the correlations between the proportion of infant deaths of each race in
      each state and the proportion of infants of that race consistently classified.
      Differential racial classification on birth and death certificates was more than
      31 times as likely with different-race than with same-race parents. The second
      hypothesis was confirmed for white, black, American Indian, and Japanese infants.
      As the U.S. population becomes more heterogeneous, attention to these
      methodologic issues becomes increasingly critical for the measurement and redress
      of differential racial health status.

PMID- 10069244
TI  - The effect of pesticide exposure on time to pregnancy.
AB  - The Ontario Farm Family Health Study provided data for examination of the effects
      of pesticide exposure on time to pregnancy. In this retrospective cohort study of
      farm couples in Ontario, Canada, the farm operator, husband, and wife completed
      questionnaires during 1991-1992. We asked about pesticides used on the farm and
      pesticide activities of the husband and wife for each month of trying to
      conceive. After exclusions, 2,012 planned pregnancies remained for analysis. We
      used an analog of the Cox proportional hazards model to calculate conditional
      fecundability ratios (conditional on pregnancy). There was no strong or
      consistent pattern of associations of pesticide exposure with time to pregnancy.
      During exposure intervals in which women participated in pesticide activities
      (during most of which the men also participated), however, 6 of 13 pesticide
      exposure categories were associated with a decrease in fecundability (conditional
      fecundability ratio range = 0.51-0.80). For exposure intervals in which only the
      men participated in pesticide activities or in which neither men nor women
      participated in pesticide activities but pesticides had been used on the farm,
      conditional fecundability ratios ranged from 0.75 to 1.50, with no apparent
      consistency among pesticide classes, chemical families, or active ingredients.

PMID- 10069245
TI  - Air pollution and infant mortality in Mexico City.
AB  - Historic air pollution episodes of the 1950s led to acute increases in infant
      mortality, and some recent epidemiologic studies suggest that infant or child
      mortality may still result from air pollution at current levels. To investigate
      the evidence for such an association, we conducted a time-series study of infant
      mortality in the southwestern part of Mexico City in the years 1993 to 1995 using
      mortality data from death registrations and air pollution measurements from a
      monitoring station we operated. Excess infant mortality was associated with the
      level of fine particles in the days before death, with the strongest association
      observed for the average concentration of fine particles during the period 3 to 5
      days previously: a 10-microg m(-3) increase in the mean level of fine particles
      during these 3 days was associated with a 6.9% excess of infant deaths (95%
      confidence interval 2.5-11.3%). Infant mortality was also associated with the
      levels of nitrogen dioxide and ozone 3 to 5 days before death, but not as
      consistently as with particles.

PMID- 10069246
TI  - Maternal occupational and hobby chemical exposures as risk factors for neural
      tube defects.
AB  - In a case-control study, we investigated whether occupational and nonoccupational
      (hobbies) chemical exposures to women in the periconceptional period increased
      their risk for having neural tube defect-affected pregnancies. Women were asked
      about occupational tasks and hobbies performed during the 3 months before through
      3 months after conception. Based on her reported occupational tasks and hobbies,
      an industrial hygienist assigned a priori defined exposure categories to each
      task and hobby. The exposure categories included 74 chemical groups, 9 "end-use"
      chemical groups, and organic solvents. Face-to-face interviews were conducted
      with mothers of 538 (88% of eligible) infants or fetuses with neural tube defect
      and mothers of 539 (88%) randomly selected, nonmalformed, live-born infants from
      a population-based 1989-1991 cohort of California births (N = 703,518). Our
      results suggested that maternal exposures in the periconceptional period to a
      variety of chemicals associated with occupational and nonoccupational activities
      did not contribute substantially to risk of neural tube defects in offspring. We
      observed no effect estimate greater than 2.0 for maternal exposures to the
      chemical agent groups studied. We did not observe substantially elevated risks
      associated with maternal exposures to any of the end-use chemical groups or to
      organic solvents. Considering occupational exposures only among women who worked
      did not substantially alter results. Adjustment for maternal vitamin use,
      race/ethnicity, or education level also did not substantially alter the observed
      associations.

PMID- 10069247
TI  - Epidemiologic evidence for a new class of compounds associated with toxic oil
      syndrome.
AB  - Toxic oil syndrome appeared in epidemic form in Spain in 1981. Epidemiologic
      studies have demonstrated that illness was caused by consumption of rapeseed oil
      that had been denatured with aniline. Chemical analyses of oil specimens
      conducted in conjunction with epidemiologic studies have established that
      consumption of specific oils containing fatty acid anilide contaminants was
      associated with increased risk for disease. New chemical analytic methods
      identified a family of compounds, the di-fatty acid esters of phenylamino propane
      diol, and one of these compounds, the 1,2-di-oleyl ester of 3-(N-phenylamino)-1,2
      propanediol (DPAP), has been found to be more strongly associated with disease
      status than the fatty acid anilides. We found the odds ratio for exposure to DPAP
      (OR = 26.4, 95% CI = 6.4-76.3) is much higher than the odds ratio for exposure to
      oleyl anilide (OR = 4.1, 95% CI = 2.2-7.8), implying that exposure to DPAP was a
      more relevant risk factor for development of toxic oil syndrome than exposure to
      oleyl anilide. In this paper, we review and present analyses of data from
      multiple studies of the possible etiologic role of DPAP in toxic oil syndrome.
      The presence of DPAP in oil collected from affected and unaffected households was
      a more specific correlate of case relatedness than was the presence of fatty acid
      anilides, and it was equally sensitive. Moreover, DPAP was found in oil from the
      only refinery whose oil was clearly associated with illness.

PMID- 10069248
TI  - Age at exposure modifies the effects of low-level ionizing radiation on cancer
      mortality in an occupational cohort.
AB  - In a cohort of 4,563 nuclear workers followed retrospectively from 1950 to 1994,
      we found that age at exposure modified the effects of external radiation dose on
      cancer mortality. Analyses involved application of conditional logistic
      regression to risk sets of age- and calendar time-matched cancer deaths, with
      covariates treated as time dependent and with cumulative radiation doses divided
      according to the age intervals in which exposure occurred. After adjustment for
      confounding factors, we found that workers exposed to external radiation after
      the age of 50 years experienced exposure-related elevations in mortality from
      cancer at any site [rate ratio (RR) = 1.98; 95% confidence interval (CI) = 0.63
      6.26], radiosensitive solid cancer (RR = 3.29; 95% CI = 1.10-9.89), and lung
      cancer (RR = 3.89; 95% CI = 1.23-12.3) substantially greater (1.6- to 3.5-fold
      greater) than were seen in coworkers exposed at all earlier ages. In contrast,
      all of the radiation doses contributing to mortality from cancers of the blood
      and lymph system were received before age 50 (for age <50, RR = 2.73 and 95% CI =
      1.46-5.10; for age > or =50, RR = 0.24 and 95% CI = 0.00-687). Our results for
      cancer of any site are consistent with the results of previous studies examining
      the effects of exposure age in nuclear workers. Thus, effects of low-level
      radiation doses may depend on exposure age, and furthermore, patterns of effect
      modification by age may differ by type of cancer.

PMID- 10069249
TI  - Maternal weight gain and preterm delivery: differential effects by body mass
      index.
AB  - We examined associations between weight gain (kg) per week of pregnancy and net
      weight gain per week of pregnancy (weight gain - birth weight/weeks of gestation
      at delivery) and preterm delivery in a population of 266,172 low-income women.
      Risk of preterm delivery was lowest among women with intermediate weight gain
      (0.35 to <0.46 kg/week) and net weight gain (0.27 to <0.37 kg/week). Both lower
      and higher weight gains and net weight gains per week were associated with an
      increased risk for preterm delivery. Associations, however, were not uniform
      across body mass index categories. Compared with women gaining 0.35 to <0.46
      kg/week, preterm risk differences (95% confidence limits) for women gaining <0.10
      kg/week were +9.5% (+6.5, +12.4) for underweight women, +6.7% (+5.6, +7.9) for
      average-weight women, +3.5% (+2.0, +4.9) for overweight women, and +0.4% (-0.4,
      +1.2) for obese women. The opposite pattern was observed with high weight gain.
      Preterm risk differences for weight gains >0.65 kg/week ranged from +0.8% (-0.7,
      +2.1) for underweight women, to +2.5% (+1.3, +3.9) for obese women. We also
      evaluated weight gain per week in the latter part of pregnancy (from week 14 to
      delivery). The same basic patterns were observed; however, variation in the
      associations across body mass index groups was not as marked.

PMID- 10069250
TI  - Changing paternity and the risk of preterm delivery in the subsequent pregnancy.
AB  - I studied whether changing a partner, and thus changing the likelihood of human
      leukocyte antigen (HLA) sharing between mating partners, affects the risk of
      preterm delivery in the subsequent pregnancy. I identified a total of 128,239
      women who had two consecutive births during 1989-1991 through data linkage of the
      California birth certificates. Paternal date of birth and names on the records of
      the two consecutive births were compared to determine whether the same father was
      reported on both records. Three cohorts of women were formed on the basis of the
      gestational age of their first delivery: <34, 34-36, and >36 weeks. If parental
      HLA sharing is associated with preterm delivery, the likelihood of HLA sharing
      was expected to be in a decreasing order from most likely among a <34-week cohort
      to least likely among a >36-week cohort. Among women in the <34-week cohort,
      changing partners resulted in a 33% reduction in the risk of early preterm
      delivery in the subsequent pregnancy compared with those who did not change
      partners [95% confidence interval (CI), 0.52-0.88]. In contrast, among women in
      the >36-week cohort, changing partners led to a 16% increase in the risk of early
      preterm delivery in the subsequent pregnancy (95% CI = 1.04-1.30). Among women in
      the 34-36-week cohort, changing partners did not affect the risk of preterm
      delivery (95% CI = 0.78-1.25). These estimates were adjusted for maternal
      race/ethnicity, age, educational level, prenatal smoking, prenatal care, parity,
      and interval from birth to conception of the subsequent pregnancy. The findings
      from this study suggest that the effect of changing paternity depends on the
      pregnancy outcome with the previous partner and support the hypothesis that
      parental HLA sharing may be related to preterm delivery.

PMID- 10069251
TI  - A woman's own birth weight and gestational age predict her later risk of
      developing preeclampsia, a precursor of chronic disease.
AB  - Preeclampsia is a major complication of pregnancy and a predictor of future
      chronic disease. We investigated the hypothesis that a woman's own weight and
      gestational age as a newborn influence her risk of developing preeclampsia later
      in life. This case-control study used linked computerized birth registry data
      from the Colorado Department of Public Health and Environment. The study subjects
      were women ages 12-20 who were born in Colorado after 1974, each of whom
      delivered a live infant in Colorado between 1990 and 1995. Cases were subjects
      with a report of eclampsia and/or preeclampsia on the 1990-1995 birth records (N
      = 345). Controls were randomly selected from subjects with uncomplicated
      pregnancies who were frequency matched to cases by year of delivery (N = 3,995).
      Records from each subject's pregnancy (1990-1995) were then linked to those from
      her own birth (1975-1983). Birth weight and gestational age, as recorded on the
      subject's birth records, were independently associated with the risk of
      developing preeclampsia after adjustment for age, parity, race/ethnicity, and
      other risk factors. The risk of preeclampsia decreased with increasing
      gestational age in a dose-dependent fashion; relative to mothers born post-term,
      adjusted odds ratios for preeclampsia ranged from 3.62 [95% confidence interval
      (95% CI) = 1.27-10.28] for mothers born at less than 34 weeks gestational age to
      1.45 (95% CI = 0.85-2.45) for those born at term. Relative to women who were born
      at 8.5 lb or more, those born in the lowest weight category (under 4.5 lb)
      appeared at greatest risk for preeclampsia (odds ratio = 5.16; 95% CI = 1.24
      21.51), although no directional trend was apparent. These findings suggest that
      women born small or premature may be at increased risk of developing preeclampsia
      as teenagers or young adults.

PMID- 10069252
TI  - Body weight, body mass index, and incident symptomatic osteoarthritis of the
      hand, hip, and knee.
AB  - Studies have shown a positive association between obesity and knee
      osteoarthritis. Studies evaluating hand or hip osteoarthritis and weight,
      however, have assessed x-ray osteoarthritis or been cross-sectional, or both, and
      results of these have been inconsistent. We assessed the association between body
      weight, body mass index, and incident symptomatic osteoarthritis in 134 matched
      case-control pairs of women who were part of a case-control study on estrogen
      replacement therapy and osteoarthritis. We identified incident symptomatic
      osteoarthritis cases of the hand, hip, and knee in women ages 20-89 years who
      were members of a health plan between January 1, 1990 and December 31, 1993. For
      each case we selected a control woman who was matched by closest date of birth to
      the case. Medical records were reviewed to obtain weight and height information
      for the period before disease onset. After controlling for estrogen use, smoking
      status, height, and health care use, we found that body weight was a predictor of
      incident osteoarthritis of the hand, hip, and knee. Odds ratios ranged from 3.0
      to 10.5 for women in the upper tertiles of weight compared with women in the
      lowest tertile. Similar associations were observed for body mass index. Our
      results suggest that obesity is associated with the development of incident
      osteoarthritis at all joints studied.

PMID- 10069253
TI  - Case-only design to measure gene-gene interaction.
AB  - The case-only design is an efficient and valid approach to screening for gene
      environment interaction under the assumption of the independence between exposure
      and genotype in the population. In this paper, we show that the case-only design
      is also a valid and efficient approach to measuring gene-gene interaction under
      the assumption that the frequencies of genes are independent in the population.
      Just as the case-only design requires fewer cases than the case-control design to
      measure gene-environment interaction, it also requires fewer cases to measure
      gene-gene interactions.

PMID- 10069254
TI  - Harvesting-resistant estimates of air pollution effects on mortality.
AB  - A number of studies have recently shown an association between particle
      concentrations in outdoor air and daily mortality counts in urban locations. In
      the public health interpretation of this evidence, a key issue is whether the
      increased mortality associated with higher pollution levels is restricted to very
      frail persons for whom life expectancy is short in the absence of pollution. This
      possibility has been termed the "harvesting hypothesis." We present an approach
      to estimating the association between pollution and mortality from times series
      data that is resistant to short-term harvesting. The method is based in the
      concept that harvesting alone creates associations only at shorter time scales.
      We use frequency domain log-linear regression to decompose the information about
      the pollution-mortality association into distinct time scales, and we then create
      harvesting-resistant estimates by excluding the short-term information that is
      affected by harvesting. We illustrate the methods with total suspended particles
      and mortality counts from Philadelphia for 1974-1988. The total suspended
      particles-mortality association in Philadelphia is inconsistent with the
      harvesting-only hypothesis, and the harvesting-resistant estimates of the total
      suspended particles relative risk are actually larger-not smaller-than the
      ordinary estimates.

PMID- 10069255
TI  - A sensitivity analysis of secular trends in risk factors and mortality based on
      cohort studies.
AB  - Because of a "healthy responder effect," secular trends in mortality based on
      cohort studies may be biased if based on responders only. Because responders are
      selected on the basis of their health at study entry, subjects just entering a
      study are not comparable with subjects who have been in the study for several
      years. The result may be an artificial increase in mortality, which impedes
      analyzing the effect of secular trends in risk factors on mortality. The
      objective of this paper is to suggest a solution by using data on nonresponders
      and applying a sensitivity analysis. We illustrate this solution with data on
      trends in smoking prevalence and all-cause mortality based on a large Danish
      cohort study with 19 years of complete follow-up on responders and nonresponders.
      Secular trends in mortality based on the whole sample vs responders only
      illustrated that results based on responders were biased. In a sensitivity
      analysis, the observed person-years of nonresponders were distributed among six
      categories of persons with respect to smoking behavior (never-smokers; ex
      smokers; noninhaling current smokers; and current smokers of 1-14, 15-24, and >
      or =25 gm tobacco per day) according to preset assumptions regarding smoking
      habits. The observed deaths among nonresponders were then distributed on the six
      smoking categories according to relative risks derived from a Poisson regression
      analysis among responders. This procedure allowed us to study the effect of
      adjustment for smoking on the unbiased secular trend in mortality. By applying
      different assumptions regarding smoking habits among nonresponders, we explored
      the effect of the assumptions on the adjusted secular trend in mortality. We
      conclude that secular trends in mortality based on responders in a cohort study
      are likely to be biased. If complete follow-up on nonresponders is available,
      this method could prove useful in other cohort studies.

PMID- 10069256
TI  - Control response proportions in population-based case-control studies in Germany.
AB  - We investigated the methods of recruitment, levels and determinants of response,
      and the calculation method of response proportions in population-based case
      control studies in Germany. We identified 26 eligible studies. The pooled
      analysis showed that the response proportion was 68% among controls and 80% among
      cases. Response proportions among controls without telephones were about 50%
      lower than for controls with telephones. We propose a new measure that indicates
      the efficacy of the recruitment strategy.

PMID- 10069257
TI  - The burden of mortality of diabetes mellitus in The Netherlands.
AB  - Our objective was to estimate the excess mortality and the reduction in life
      expectancy related to diabetes mellitus. We developed a life table to describe
      the Dutch population in two states, diabetic and non-diabetic, using age- and sex
      specific prevalence of diabetes mellitus and risks of dying for diabetic
      subjects. We compared the calculated excess deaths with registered deaths. The
      cause-of-death registration practice underestimates diabetes-related mortality.
      The method used in this study, combining mortality data with data from
      epidemiologic studies, provides an assessment of the impact of diabetes on the
      Dutch population.

PMID- 10069258
TI  - Body mass index and risk of renal cell carcinoma.
AB  - To examine the association between body mass index and renal cell carcinoma risk,
      we analyzed data from a case-control study of members of a health maintenance
      organization in western Washington State. We identified cases diagnosed between
      1980 and 1995 through a population-based cancer registry. We selected controls
      from membership files. We collected adult weight and height from medical records.
      Increased body mass index was associated with increases in risk for both men and
      women (for the top quartile relative to the bottom quartile of maximum body mass
      index: in women, OR = 3.3, 95% CI = 1.2-8.7; in men, OR = 2.3, 95% CI = 1.2-4.5).

PMID- 10069259
TI  - A case-cohort study on prostate cancer risk in relation to family history of
      prostate cancer.
AB  - We investigated the risk of prostate cancer in relation to a family history of
      prostate cancer in 58,279 men ages 55-69 years. We found 704 incident cases after
      6.3 years of follow-up. Rate ratios and 95% confidence intervals for having an
      affected vs nonaffected father and brother were, respectively 1.44 (0.80-2.58)
      and 5.57 (1.61-19.26). We found no evidence for an increasing risk with an
      increasing percentage of affected family members. The associations we observed
      were stronger for cases diagnosed before age 70 compared with cases diagnosed
      after age 70 and for advanced compared with localized tumors.

PMID- 10069260
TI  - Assessing the effects of a therapy by comparing the experience of currently
      treated and formerly treated patients.

PMID- 10069261
TI  - Fumonisins and neural tube defects in South Texas.

PMID- 10069262
TI  - Reproductive outcomes after radiation exposure.

PMID- 10069263
TI  - Drinking water and spontaneous abortion.

PMID- 10069264
TI  - Preserving public health values.

PMID- 10069265
TI  - Morphological variation analysis of the repeatability of soccer offensive
      schemes.
AB  - A landmark-based statistical method, morphological variation analysis, for the
      quantification of the repeatability in the arrangement of body segments during
      the execution of sport actions has recently been developed. A two-dimensional
      shape is produced and its morphology is studied. The method was used to measure
      the within-team variability of the relative positions of players during the
      execution of offensive schemes in soccer. Two junior soccer teams of different
      technical abilities (semi-professional vs. amateur), each playing two
      standardized offensive schemes of different difficulty (easier: throw-in; more
      difficult: wing attack) were filmed. Each scheme was repeated 25 (semi
      professionals) or 10 (amateurs) times. For each repetition, the position of the
      players in a single significant frame was analysed using morphological variation
      analysis. The reproducibility of both schemes was higher among the semi
      professionals than among the amateurs (two-way analysis of variance, P<0.005).
      The repeatability of the players' relative positions was related to the
      difficulty of the scheme and the technical level of the team. Among the amateurs,
      the throw-in was more reproducible than the wing attack (Student's t-test,
      P<0.005). The method not only allows the quantification of collective (team)
      coordination, but also the separation of the influence of individual players.

PMID- 10069266
TI  - Determining propulsive force in front crawl swimming: a comparison of two
      methods.
AB  - To evaluate the propulsive forces in front crawl arm swimming, derived from a
      three-dimensional kinematic analysis, these values were compared with mean drag
      forces. The propulsive forces during front crawl swimming using the arms only
      were calculated using three-dimensional kinematic analysis combined with lift and
      drag coefficients obtained in fluid laboratories. Since, for any constant
      swimming speed, the mean propulsive force should be equal to the mean drag force
      acting on the body of the swimmer, mean values of the calculated propulsive
      forces were compared with the mean drag forces obtained from measurements on a
      Measuring Active Drag (MAD) system. The two methods yielded comparable results,
      the mean difference between them being only 5% (2 N). We conclude that propulsive
      forces obtained from three-dimensional kinematic analysis provide realistic
      values. The calculation of the propulsive force appears to be rather sensitive to
      the point on the hand at which the velocity is estimated and less sensitive to
      the orientation of the hand.

PMID- 10069267
TI  - Submaximal exercise and maturation in 12-year-olds.
AB  - The aim of this study was to examine the maturation responses of young people to
      submaximal treadmill exercise. Body mass was controlled using both the
      conventional ratio standard and allometric modelling. Ninety-seven boys and 97
      girls with a mean age of 12.2 years completed a discontinuous, incremental
      exercise test to voluntary exhaustion. We measured peak oxygen uptake (VO2peak)
      and VO2 when running at 8, 9 and 10 km x h(-1). Sexual maturation was assessed
      visually using Tanner's indices of pubic hair. Peak VO2 was significantly higher
      in boys (P<0.001); this was still the case when the influence of body mass was
      covaried out. During submaximal exercise, no significant differences in absolute
      VO2 were observed between the sexes (P>0.05); however, values of VO2, expressed
      both in ratio with body mass and adjusted for body mass using allometry, were
      significantly greater in boys than in girls (P<0.001). For absolute VO2,
      significant main effects (P<0.05) were seen for maturity at each exercise stage.
      With the influence of body mass controlled using either the ratio standard or
      allometry, no significant main effects (P>0.05) for maturity were observed. Our
      results indicate that boys are less economical than girls while running at 8-10
      km x h(-1) and that, independently of body mass, maturation does not influence
      the VO2 response to submaximal exercise.

PMID- 10069268
TI  - The effect of induced mood states on performance profile areas of perceived need.
AB  - The performance profile technique is now widely used by a range of sports
      scientists, usually as the first step in implementing a training programme. The
      aim of this study was to examine the effect of altered mood states on areas of
      perceived need for an individual identified by the performance profile. Sixty
      seven university sports science students (30 females, 37 males) participated in
      the study. They completed their performance profile and a shortened version of
      the Bi-polar Profile of Mood States before and after four separate mood
      manipulation treatments (happy, sad, neutral, control). The participants were
      allocated at random to one of four groups and completed the treatments in a
      counterbalanced order. Mood manipulation checks identified that both the happy
      and sad manipulations were successful. Profile areas of perceived need,
      identified through discrepancies in an individual's perceptions of ideal and
      current state, were not affected by the sad and neutral manipulations or by the
      control condition. However, areas of perceived need were significantly lower
      after the happy mood manipulation than before the treatment. Our results show
      that asking individuals to complete their profiles when in a happy mood state is
      likely to affect judgements and result in an underestimation of perceived need
      for improvement.

PMID- 10069269
TI  - The effects of high-intensity intermittent exercise on saliva IgA, total protein
      and alpha-amylase.
AB  - The aim of this study was to assess the effect of an acute bout of high-intensity
      intermittent exercise on saliva IgA concentration and alpha-amylase activity,
      since this type of training is commonly incorporated into the training programmes
      of endurance athletes and games players. Eight well-trained male games players
      took part in the study. They reported to the laboratory after an overnight fast
      and performed a 60-min cycle exercise task consisting of twenty 1-min periods at
      100% VO2max, each separated by 2 min recovery at 30% VO2max. Unstimulated whole
      saliva was collected over a 5-min period into pre-weighed tubes and analysed for
      total protein, saliva IgA and alpha-amylase. The saliva flow rate ranged from
      0.08 to 1.40 ml x min(-1) at rest and was not significantly affected by the
      exercise. The performance of the intermittent exercise bout did not affect the
      saliva IgA concentration, but caused a five-fold increase in alpha-amylase
      activity (P<0.01 compared with pre-exercise) and a three-fold increase in total
      protein concentration (P<0.01). These returned to pre-exercise values within 2.5
      h post-exercise. It has been suggested that IgA concentration should be expressed
      as the ratio to total protein concentration, to correct for any concentrating
      effect due to evaporative loss of saliva water when breathing through the mouth
      (as in strenuous exercise). The present study clearly demonstrates that this is
      not appropriate, since there is an increase in salivary protein secretion rate
      immediately after exercise (571+/-77 microg x min(-1) compared with 218+/-71
      microg x min(-1) pre-exercise; P<0.05). The increased saliva alpha-amylase
      activity after exercise may improve the protective effect of saliva, since this
      enzyme is known to inhibit bacterial attachment to oral surfaces. The saliva
      alpha-amylase secretion rate was lower immediately pre-exercise than at any other
      instant, which may have been due to anticipatory psychological stress, although
      the subjects were all familiar with interval exercise. This emphasizes the need
      for true resting non-stressed control conditions in future studies of the effects
      of exercise on saliva constituents.

PMID- 10069270
TI  - Heart rate and blood lactate responses during competitive Olympic boardsailing.
AB  - The rules of competitive boardsailing events were changed before the Atlanta
      Olympic Games. Pumping the sail (pulling repeatedly on the rig) is now allowed
      and the duration of races has been shortened. Eight members of the French
      national team (mean age 23+/-2.7 years) participated in this study. Their cardiac
      and metabolic responses were assessed by measuring heart rate and blood lactate
      concentration during various competitive events in two strengths of wind (light
      vs. moderate). Heart rate was higher in light (87.4+/-4.3% HRmax; mean racing
      time 37 min) than in moderate wind conditions (82.9+/-5.3% HRmax; mean racing
      time 33 min). The mean post-race blood lactate concentration (5.2+/-1.0 mmol x l(
      1)) was not affected by the wind conditions. Mean heart rate was highest during
      downwind legs (88.0+/-3.1% HRmax; duration 7-10 min). The races consisted of two
      laps, the first of which induced significantly higher cardiac demands than the
      second. We conclude that the changes to the rules of competitive boardsailing
      have increased the cardiac and metabolic efforts involved.

PMID- 10069271
TI  - A comparison of physiological responses to rowing on friction-loaded and air
      braked ergometers.
AB  - The physiological responses of 10 trained rowers to a progressive incremental
      rowing protocol to exhaustion were investigated on Gjessing, Rowperfect fixed
      mechanism and Rowperfect free-mechanism rowing ergometers. Heart rate, oxygen
      uptake (VO2), ventilation (VE) and blood lactate were determined at matched power
      values for each ergometer. The mean power and heart rate at the lactate anaerobic
      threshold were determined by graphical interpolation of data for each ergometer.
      Analysis of variance and linear regression showed differing responses at matched
      power and an approximate 40-50 W difference in power at the lactate anaerobic
      threshold when comparing the friction-loaded Gjessing with the air-braked
      Rowperfect fixed and Rowperfect free ergometers (P<0.01). No significant
      differences were noted when comparing the air-braked Rowperfect fixed and
      Rowperfect free ergometers. However, comparisons of VO2, VE and blood lactate at
      given heart rates and of heart rate at the lactate anaerobic threshold showed no
      significant differences between ergometers. Our results indicate similar
      physiological profiles for all ergometers tested when compared at equivalent
      heart rates, but differences when compared at matched power. A direct comparison
      of the data from Gjessing (friction-loaded) with Rowperfect fixed and Rowperfect
      free (air-braked) ergometers would therefore require a correction factor for
      inter-ergometer variation in displayed power data.

PMID- 10069272
TI  - The impact of collective efficacy beliefs on effort and persistence in a group
      task.
AB  - Collective efficacy is an important determinant of the motivation of individuals
      within groups, with increases in collective efficacy producing more effort in a
      task and greater persistence when faced with failure. To test hypotheses
      concerning the impact of collective efficacy on effort and persistence,
      participants (n = 22) were assigned to triads (consisting of the participant and
      two confederates) and performed three time trials on cycle ergometers. After
      trial 1, the participants were assigned to either a high or low collective
      efficacy condition, receiving appropriate bogus performance feedback. All groups
      received failure feedback after trial 2. Effort was assessed by performance time
      and maximum heart rate (HRmax) achieved during performance. A 2 (collective
      efficacy condition) x 3 (trials) analysis of variance with repeated measures on
      trials revealed significant interaction effects for both performance time and
      HRmax. Fisher's least significant difference post-hoc tests indicated that,
      following efficacy manipulation, groups low in collective efficacy significantly
      reduced both their performance time and HRmax, whereas groups high in collective
      efficacy maintained performance and HRmax. However, predictions concerning the
      impact of failure on persistence were not supported. Our results provide partial
      support for the role of collective efficacy in team sports.

PMID- 10069273
TI  - Changes in muscle-tendon length during the take-off of a running long jump.
AB  - The aims of this study were to determine: (1) the modes of action of selected
      muscles of the supporting leg during the take-off of a running long jump; (2)
      whether the instant at which maximum knee flexion is recorded is a valid
      indicator of the instant these muscles change their modes of action; and (3) the
      relationships between the actions of these muscles and the change in the vertical
      velocity of the centre of mass during the take-off. Eleven elite, female long
      jumpers performed six jumps from a full-length approach. A model of selected
      muscles of the jumping leg was developed to estimate muscle-tendon lengths from
      segment positions obtained using cinematography. Only half of the muscles
      exhibited a lengthening-shortening sequence of activity. The instant at which
      maximum knee flexion was recorded was a poor indicator of when the muscles
      changed from eccentric to concentric activity. The more the vasti muscles were
      stretched, the larger the gain in vertical velocity; the longer the triceps surae
      muscles at touchdown, the more they were stretched, and the faster they were
      stretched, the larger the gain in vertical velocity. Enhancement through use of
      the stretch-shortening cycle did not make a significant contribution to vertical
      velocity via the actions of the vasti and triceps surae muscles.

PMID- 10069274
TI  - Toward the goal of optimal cardiac anesthesia.

PMID- 10069275
TI  - Continuous infusion versus bolus administration of sufentanil and midazolam for
      mitral valve surgery.
AB  - OBJECTIVE: In the present study, the authors compared continuous infusion to
      bolus administration of sufentanil and midazolam in patients undergoing mitral
      valve surgery. The purpose of the study was to evaluate the hemodynamic
      variability, total dose, effective plasma drug concentrations, and simplicity of
      the two anesthetic techniques. DESIGN: Prospective, randomized study. SETTING:
      University hospital. PARTICIPANTS: Thirty patients scheduled for elective mitral
      valve surgery. INTERVENTIONS: Induction of anesthesia was similar in both groups
      and consisted of sufentanil, up to 2 microg/kg, and midazolam, 0.05 to 0.15
      mg/kg, followed by atracurium, 0.5 mg/kg. Anesthesia was maintained in the bolus
      group with predetermined boluses of sufentanil, 2 microg/kg, and midazolam, 0.03
      mg/kg. Boluses were not administered if blood pressure was within 20% of
      baseline. The continuous-infusion group received sufentanil, 3.6 microg/kg/h, and
      midazolam, 0.08 mg/kg/h, started immediately after induction. The infusion rate
      was reduced to sufentanil, 1.8 microg/kg/h, and midazolam, 0.04 mg/kg/h, after
      sternotomy and was discontinued at skin closure. Atracurium was infused at a rate
      of 0.5 mg/kg/h up to sternal closure in both groups. No inhalation agents were
      used. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variability between the groups
      was not significant. Total sufentanil dose was 773 +/- 186 microg in the
      continuous-infusion group and 610 +/- 184 microg in the bolus group (p = 0.01).
      Total midazolam dose was 14.4 +/- 3 mg and 11.2 +/- 3 mg in the continuous
      infusion and bolus groups, respectively. There were 3.46 (range, 0 to 7)
      additional bolus injections in the bolus group and 0.31 (range, 0 to 1) in the
      continuous-infusion group (p < 0.001). Plasma sufentanil concentrations at
      extubation were similar in both groups (0.5 ng/mL). Plasma midazolam
      concentrations at extubation in the bolus group (17 +/- 6.7 ng/mL) were similar
      to those in the continuous-infusion group (23 +/- 5 ng/mL). CONCLUSION: The
      simplicity of the continuous infusion is a major advantage. This technique
      provides hemodynamically safe and stable conditions similar to those of bolus
      administration.

PMID- 10069276
TI  - Does sufentanil concentration influence isoflurane requirements during coronary
      artery bypass grafting?
AB  - OBJECTIVE: To search for concentration-related suppression of hemodynamic
      responsiveness by sufentanil. DESIGN: Prospective, randomized, double-blind
      study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective
      coronary artery bypass grafting (CABG). INTERVENTION: Patients were assigned to
      target effect-site sufentanil concentrations of 1.5 ng/mL (group L; n = 14), 3.0
      ng/mL (group M; n = 13), or 4.5 ng/mL (group H; n = 12). Sufentanil was
      administered by computer-assisted continuous infusion. Isoflurane was used to
      maintain intraoperative hemodynamics near preoperative values. MEASUREMENTS AND
      MAIN RESULTS: Hemodynamics, the electroencephalographic spectral edge (SE95), and
      end-tidal isoflurane concentration (ET-ISO) were measured every 10 to 30 seconds
      during the prebypass period. Serum sufentanil concentration was measured at
      intervals. Prebypass serum sufentanil concentrations were stable, averaging 3.0
      +/- 0.7, 5.1 +/- 1.1, and 7.1 +/- 1.3 ng/mL in groups L, M, and H, respectively.
      The groups did not differ with respect to the speed of induction, intraoperative
      hemodynamics, incidence of isoflurane use, or isoflurane concentrations required.
      ET-ISO and serum sufentanil levels were not correlated. Among seven group L
      patients who did not require isoflurane, the average prebypass serum sufentanil
      concentration ranged from 1.7 to 3.3 ng/mL. CONCLUSION: Sufentanil does not
      induce concentration-related suppression of hemodynamic responsiveness over the
      range studied. A stable serum sufentanil concentration of 3.0 +/- 0.7 ng/mL
      induces the maximal opioid effect and need not be exceeded in patients undergoing
      CABG. A sufentanil concentration of 1.7 ng/mL provides clinically adequate
      anesthesia without supplementation in some premedicated patients undergoing CABG.

PMID- 10069277
TI  - Total intravenous anesthesia with remifentanil and propofol for implantation of
      cardioverter-defibrillators in patients with severely reduced left ventricular
      function.
AB  - OBJECTIVE: To determine the cardiocirculatory effects of total intravenous
      anesthesia (TIVA) using remifentanil and propofol in high-risk cardiac surgical
      patients. DESIGN: Prospective study of 20 patients undergoing first-time
      implantation of a cardioverter-defibrillator (ICD). SETTING: Major, community,
      university-affiliated hospital. PARTICIPANTS AND INTERVENTIONS: In 20 patients
      with severely reduced left ventricular function (left ventricular ejection
      fraction <30%) undergoing first-time implantation of an ICD, TIVA using
      remifentanil and propofol was performed. MEASUREMENTS AND MAIN RESULTS: Extensive
      hemodynamic monitoring using a pulmonary artery catheter was performed: (T1)
      before induction of anesthesia, (T2) after intubation, (T3) after skin incision,
      (T4) after first defibrillation, and (T5) 10 minutes after extubation. Propofol,
      3.0 +/- 0.6 mg/kg/h (range, 1.9 to 4.4 mg/kg/h), and remifentanil, 0.30 +/- 0.05
      microg/kg/min (range, 0.21 to 0.40 microg/kg/min), were used. Total costs added
      up to US $44.60 per patient. Patients could be extubated within 12.5 +/- 4.2
      minutes after stopping anesthesia. There were significant decreases in heart rate
      (HR; from 77 +/- 12 to 57 +/- 10 beats/min [T3]), mean arterial blood pressure
      (MAP; from 98 +/- 14 to 70 +/- 12 mmHg [T2]), and systemic vascular resistance
      (from 1,551 +/- 309 to 1,233 +/- 274 dyne x s x cm(-5) [T2]). Cardiac index (CI)
      slightly decreased only at T3 (from 2.46 +/- 0.42 to 1.92 +/- 0.29 L/min/m2; p =
      0.04). The decrease in MAP could easily be treated by volume infusion in most
      patients (17 patients). Sixty-five percent of the patients needed dobutamine to
      increase CI to greater than 2.0 L/min/m2 (mean dose, 2.2 +/- 1.8 microg/kg/min).
      Dobutamine could be stopped before extubation in all patients. No patient needed
      sustained inotropic or ventilatory support and intensive care therapy could be
      avoided. CONCLUSION: TIVA using remifentanil and propofol in patients with
      severely reduced left ventricular function is safe, well-controllable, and allows
      early extubation after implantation of an ICD. Because patients without
      complications did not need a postoperative intensive care stay, costs may be
      considerably reduced.

PMID- 10069278
TI  - A two-center study evaluating the hemodynamic and pharmacodynamic effects of
      cisatracurium and vecuronium in patients undergoing coronary artery bypass
      surgery.
AB  - OBJECTIVE: To determine the hemodynamic and pharmacodynamic effects of rapid
      bolus administration of cisatracurium compared with vecuronium. DESIGN: A
      randomized, prospective, double-blind study. SETTING: Tertiary-care university
      hospitals. PARTICIPANTS: Seventy-nine adult patients with diagnosed coronary
      artery disease (CAD). INTERVENTION: Elective coronary artery bypass graft surgery
      (CABG). MEASUREMENTS AND MAIN RESULTS: Patients were randomly divided into four
      groups. Patients received a rapid bolus of two or four times the 95% peak
      depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or
      vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all
      patients received a rapid bolus administration of either study drug. Maintenance
      of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic.
      Patients were monitored with radial and pulmonary artery catheters and
      electromyography. End points of the study were hemodynamic stability at
      induction, after bolus administration of study drugs, and after intubation; the
      quality of intubating conditions; drug interventions to correct hemodynamic
      instability; the onset, duration, and recovery of neuromuscular function; and
      drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a
      similar proportion in all four groups after induction while, following study drug
      administration, MAP and HR did not change significantly. Both cisatracurium
      groups required more boluses to maintain neuromuscular block, but spontaneous
      recovery rates were faster. Both agents, but cisatracurium to a lesser degree,
      showed increased duration with repeated maintenance doses. Both agents afforded
      good to excellent intubating conditions, but the cost of cisatracurium was
      significantly less. CONCLUSION: The authors conclude there is no evidence of a
      hemodynamic difference between the two neuromuscular blocking drugs (NMBDs).
      There are some clinical and cost advantages in favor of cisatracurium.

PMID- 10069279
TI  - Atracurium during thoracic surgery: impaired efficiency in septic processes.
AB  - OBJECTIVE: The aim of the study was to examine whether the neuromuscular blocking
      potency of atracurium changes in patients with a septic intrathoracic process.
      DESIGN: Prospective clinical study. SETTING: Community hospital. PARTICIPANTS:
      Thirty patients who underwent thoracic surgery for resection of a pulmonary
      carcinoma were examined. Fifteen patients showed typical signs of a concomitant
      bacterial superinfection (infection group), 15 age-matched patients without
      infection served as the control (no-infection) group. INTERVENTIONS: Relaxation
      was induced with atracurium, 0.6 mg/kg intravenously for intubation, followed by
      a continuous infusion to maintain a 90% neuromuscular blockade. Relaxometry was
      performed electromyographically using the Datex Relaxograph by stimulating the
      ulnar nerve next to the wrist. MEASUREMENTS AND MAIN RESULTS: The onset time was
      significantly longer (5.3 +/- 2.9 v 3.3 +/- 1.2 minutes; p < 0.05), and the
      recovery phase (DUR 10%) was significantly shorter (23.5 +/- 8.6 v 36.9 +/- 7.3
      minutes; p < 0.001) in the infection group compared with the controls. The
      infusion rate within the first hour of continuous application was 77.4% higher in
      the infection group than in the control group (11.0 +/- 2.9 v 6.2 +/- 1.0
      microg/kg/min; p < 0.001). CONCLUSION: The study showed that septic intrathoracic
      processes cause a clear reduction of the neuromuscular blocking potency of
      atracurium. To guarantee adequate muscle relaxation in such cases, precise
      neuromuscular monitoring is highly advisable.

PMID- 10069280
TI  - The influence of nitrous oxide to supplement fentanyl/low-dose propofol
      anesthesia on transcranial myogenic motor-evoked potentials during thoracic
      aortic surgery.
AB  - OBJECTIVE: Intraoperative monitoring of myogenic motor evoked potentials to
      transcranial electrical stimulation (tc MEPs) is a new method to assess the
      integrity of the motor pathways. The authors studied the effects of 50% nitrous
      oxide (N2O) and a low-dose propofol infusion on tc MEPs paired electrical
      stimulation during fentanyl anesthesia with partial neuromuscular blockade.
      DESIGN: Cross-over study. SETTING: St Antonius Hospital, Nieuwegein, The
      Netherlands. PARTICIPANTS: Ten patients scheduled to undergo surgery on the
      thoracoabdominal aorta were studied; 6 women aged 54 to 69 years and 4 men aged
      68 to 77 years. INTERVENTIONS: After achieving a stable anesthetic state and
      before surgery, tc MEPs were recorded during four 15-minute periods: (I)
      air/oxygen (O2; F(I)O2 = 50%); propofol target blood concentration, 0.5
      microg/mL; (II) N2O/O2 (F(I)O2 = 50%); propofol target blood concentration, 0.5
      microg/mL; (III) N2O/O2 (F(I)O2 = 50%; propofol target blood concentration, 1.0
      microg/mL; and (IV) air/O2 (F(I)O2 = 50%); propofol target blood concentration,
      1.0 microg/mL. MEASUREMENTS AND MAIN RESULTS: Tc MEPs were recorded from the
      right extensor digitorum communis muscle and the right tibialis anterior muscle.
      The right thenar muscle was used for recording the level of relaxation; the T1
      response was maintained at 40% to 70% of the control compound muscle action
      potential. There was no significant difference in onset latency among the four
      phases. The addition of N2O and doubling the target propofol infusion to 1.0
      microg/mL resulted in a 40% to 50% reduction of tc MEP amplitude recorded in the
      extensor digitorum communis muscle and tibialis anterior muscle (p < 0.01).
      During each phase, tc MEPs could be elicited and interpreted, except in one
      patient, in whom no tc MEPs could be elicited in the leg because of technical
      problems. CONCLUSION: The data indicate that tc MEP monitoring is feasible during
      low-dose propofol, fentanyl/50% N2O in 02 anesthesia and partial neuromuscular
      blockade.

PMID- 10069281
TI  - Pulmonary air trapping during two-lung and one-lung ventilation.
AB  - OBJECTIVE: Evaluation of the magnitude of pulmonary air trapping during routine
      thoracic surgery and single-lung transplantation. DESIGN: Prospective study on
      consecutive patients. SETTING: Single institution, university hospital.
      PARTICIPANTS: Sixteen patients with no or moderate obstructive lung disease
      undergoing routine thoracic surgery (group 1), six patients with severe emphysema
      (group 2), and six patients with severe fibrosis (group 3) undergoing single-lung
      transplantation. INTERVENTIONS: Occlusion maneuver timed at the end of expiration
      to measure auto-positive end-expiratory pressure (auto-PEEP) and trapped volume
      (delta FRC). The maneuver was performed during two-lung ventilation in supine
      (2LV supine) and lateral decubitus (2LV lateral) positions and during one-lung
      ventilation (OLV) in lateral decubitus position. At the same time, airway
      pressures and PaO2 measurements were performed. MEASUREMENTS AND MAIN RESULTS: In
      group 1, consistent values of auto-PEEP and delta FRC occurred only during OLV:
      4.8 +/- 2.5 cm H2O and 109 +/- 61 mL (mean +/- standard deviation). In group 2,
      auto-PEEP and delta FRC values were 11.7 +/- 6.9 cm H2O and 355 +/- 125 mL during
      2LV supine, 8.8 +/- 5.7 cm H2O and 320 +/- 122 mL during 2LV lateral, and 15.9 +/
      3.9 cm H2O and 284 +/- 45 mL during OLV. In group 3, pulmonary air trapping was
      low. For the three groups together, auto-PEEP and delta FRC (p < 0.0001) related
      inversely to the ratio of forced expired volume in 1 second (FEV1) to forced
      vital capacity (FVC) expressed in percent (FEV1/FVC%) during OLV. In contrast,
      there was no correlation between PaO2 and auto-PEEP or delta FRC. CONCLUSION:
      Pulmonary air trapping must be suspected in patients with no or moderate
      obstructive lung disease during OLV and in those with severe obstructive disease
      as soon as 2LV is initiated.

PMID- 10069282
TI  - A new bronchial blocker tube for one-lung ventilation.
AB  - One-lung ventilation is used to facilitate thoracic and cardiac surgery. This
      article describes the development and clinical use of a new device, the bronchial
      blocker tube, to establish one-lung ventilation. The bronchial blocker tube has
      two circular lumen joined together, one for ventilation and one for acceptance of
      a bronchial blocker. In this setting, the bronchial blocker is a separate device
      which is replaceable, rotatable, and removable. In the authors' experience, the
      bronchial blocker tube was effective and easy to use.

PMID- 10069283
TI  - Endovascular aortic repair is associated with greater hemodynamic stability
      compared with open aortic reconstruction.
AB  - OBJECTIVE: Examination of overall hemodynamic stability in patients undergoing
      endovascular aortic repair (EAR) compared with open aortic repair (OAR). DESIGN:
      Retrospective study. SETTING: University hospital setting. PARTICIPANTS: Seventy
      two patients undergoing OAR and 17 patients undergoing EAR were studied.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic parameters were
      extracted every 15 seconds from computerized anesthesia records. Median values
      were calculated for every 2-minute epoch, and the absolute value of the
      fractional change in median (|FCM|) from epoch to epoch was calculated for a
      maximum of 5 hours during the intraoperative period. The incidence of extremes in
      hemodynamic parameters was compared. Data are presented as median and
      interquartile ranges. The frequency of |FCM| greater than 0.06 for mean arterial
      pressure (MAP) was significantly greater in the OAR compared with the EAR group
      (0.37 [0.30, 0.46] vs 0.14 [0.11, 0.21], p < 0.0001), implying greater stability
      in MAP during EAR. Similarly, the mean pulmonary artery pressures (MPAPs) were
      significantly more stable during EAR compared with OAR (frequency of |FCM| >
      0.07: EAR, 0.20 [0.16, 0.27] vs OAR, 0.32 [0.26, 0.391; p < 0.01). No intergroup
      differences were detected in heart rate (HR), systolic (SPAP) or diastolic
      pulmonary artery pressures (DPAP), or central venous pressures (CVPs). With the
      exception of a greater incidence of low CVP during EAR, there were no significant
      differences in the frequency of extremes of hemodynamic values between groups.
      CONCLUSION: These results show improved hemodynamic stability during EAR compared
      with OAR.

PMID- 10069284
TI  - Morbidity outcome in patients with hypertrophic obstructive cardiomyopathy
      undergoing cardiac septal myectomy: early-extubation anesthesia versus high-dose
      opioid anesthesia technique.
AB  - OBJECTIVE: Anesthetic management of patients with hypertrophic obstructive
      cardiomyopathy (HOCM) undergoing septal myectomy is challenging. The morbidity
      outcome of early-extubation anesthesia (EEA), or fast tracking, versus high-dose
      opioid (HDO) anesthesia was studied. DESIGN: Retrospective study. SETTING:
      University teaching hospital. PARTICIPANTS: One hundred seventy-five cardiac
      septal myectomy patients (EEA, n = 53; HDO, n = 122). INTERVENTIONS: EEA
      technique consisted of low-dose fentanyl, 10 to 15 microg/kg; propofol infusion;
      midazolam; and inhalation agent. HDO technique consisted of fentanyl, 50 to 100
      microg/kg, and benzodiazepines, with or without an inhalation agent. Demographic
      data, preoperative symptoms, and data on anesthesia management and postoperative
      complications were recorded. MEASUREMENTS AND MAIN RESULTS: There were no
      differences between the groups (EEA v HDO, respectively) regarding age, sex,
      preoperative symptoms (dyspnea, 89% v 79%; palpitations, 28% v 26%; angina, 47% v
      61%; syncope, 47% v 41%), redo surgery, or combined surgery. Mean +/- standard
      deviation time to tracheal extubation was 7.2 +/- 5.3 hours in EEA versus 19.4 +/
      10.5 hours in HDO patients (p < 0.0001). Intensive care unit (ICU) stay was
      significantly shorter in EEA versus HDO patients (2.2 v 3.0 days; p < 0.005),
      with the trend toward earlier hospital discharge (9.7 v 11.3 days; p = 0.09).
      There was a high requirement for temporary pacing in both groups immediately
      postoperatively (EEA, 60% v HDO, 48%; p > 0.08). Permanent pacemaker insertion
      postoperatively was required in 7 of 53 patients (13%) in the EEA group and 11 of
      122 patients (9%) in the HDO group (p > 0.25). Atrial arrhythmias occurred
      postoperatively in 25% of EEA patients versus 34% of HDO patients (p > 0.08).
      CONCLUSION: EEA facilitates earlier tracheal extubation by 12 hours in patients
      with HOCM undergoing septal myectomy, significantly shortening ICU stay by 1 day
      without increasing perioperative cardiac morbidity or mortality.

PMID- 10069285
TI  - Heparin management test versus activated coagulation time during cardiovascular
      surgery: correlation with anti-Xa activity.
AB  - OBJECTIVE: To compare the abilities of the heparin management test (HMT) and the
      activated coagulation time (ACT) to provide a measurement of heparin effect in
      patients undergoing cardiac or peripheral vascular surgery. These measurements of
      heparin effect were also compared with measurements of heparin concentrations
      tested by anti-Xa activity. A secondary objective was to compare the performance
      of the noncitrated HMT with that of the citrated HMT. DESIGN: A prospective
      study. SETTING: A single-center study conducted in a university hospital.
      PARTICIPANTS: After human investigation committee approval and informed consent
      were obtained, adult patients undergoing cardiac or peripheral vascular surgery
      were included in this study. INTERVENTIONS: In both surgical groups, blood was
      sampled for ACT, HMT, and anti-Xa activity. Each HMT was performed on both
      noncitrated and citrated samples. MEASUREMENTS AND MAIN RESULTS: As an indicator
      of heparin effect, the HMT had a strong correlation with the ACT (r = 0.899; p <
      0.01). In addition, the HMT had a significantly stronger correlation with anti-Xa
      activity than the ACT (p < 0.01). The correlation obtained from the noncitrated
      samples was identical with that obtained from the citrated samples (r = 0.819; p
      < 0.001 for both groups). CONCLUSION: The ability of the HMT and the ACT to
      measure heparin effect was similar. The HMT performed better than the ACT when
      using anti-Xa activity as a measure of heparin concentration. Noncitrated HMT
      results were similar to citrated HMT results, thus supporting the use of fresh
      whole blood for testing purposes.

PMID- 10069286
TI  - Near-site monitoring of the antiplatelet drug abciximab using the Hemodyne
      analyzer and modified thrombelastograph.
AB  - OBJECTIVE: This investigation examines the hypothesis that the antiplatelet
      effect of abciximab and its reversal can be monitored using the Hemodyne
      (Hemodyne, Inc, Midlothian, VA) analyzer and modified Thrombelastograph
      (Haemoscope, Skokie, IL). DESIGN: In vitro dose-response and reversal study.
      SETTING: Anesthesia Research (Dallas, TX) and Special Studies Coagulation
      Laboratories (Washington, DC). PARTICIPANTS: Nine healthy volunteers.
      INTERVENTIONS: The addition of increasing concentrations of abciximab, 0 to 10
      microg/mL, and purified fibrinogen, 50 to 400 mg/dL. The reversal of abciximab, 4
      microg/mL, with the addition of fresh platelet-rich plasma (PRP) sufficient to
      increase the platelet concentration by approximately 10%. MEASUREMENTS AND MAIN
      RESULTS: Platelet aggregation and platelet contractile force using the Hemodyne
      analyzer were used as platelet-specific measurements. The Thrombelastograph
      maximum amplitude (MA) for platelets (MA(PLT)) was calculated by subtracting the
      MA from a platelet-poor plasma (PPP) sample (MA(ppp)) determined in one
      thromboelastography well from that of whole-blood MA (MA(WB)) run simultaneously
      in the second thromboelastography well. The addition of abciximab, 0 to 10
      microg/mL, resulted in significant concentration-dependent reductions in platelet
      aggregation (p < 0.001), platelet contractile force (p < 0.001), and MA(PLT) (p <
      0.001). Platelet contractile force (p < 0.03) and MA(PLT) (p < 0.05) were
      significantly more responsive than MA(WB) to the effect of abciximab, 4
      microg/mL, and its reversal with the addition of fresh PRP. Purified fibrinogen
      concentration directly correlated with thromboelastography MA (r(s) = 0.97; p <
      0.001), yet had no effect on platelet contractile force. The addition of
      abciximab had no measurable influence on the MA(ppp). CONCLUSION: This in vitro
      study suggests that the Hemodyne analyzer and modified Thrombelastograph might be
      clinically useful methods to monitor the platelet inhibitory effects of agents
      such as abciximab.

PMID- 10069287
TI  - Initial misinterpretation of a transesophageal echocardiographic image: potential
      for alteration of a planned minimally invasive procedure.

PMID- 10069288
TI  - Transesophageal echocardiography in monitoring of intrapulmonary embolism during
      inferior vena cava tumor resection.

PMID- 10069289
TI  - Use of transesophageal echocardiography to guide the anesthetic management of
      cesarean section in a patient with hypertrophic cardiomyopathy.

PMID- 10069290
TI  - Bleeding from a pulmonary artery catheter temperature connection port.

PMID- 10069291
TI  - Mechanisms of ischemic preconditioning and clinical implications for multiorgan
      ischemic-reperfusion injury.

PMID- 10069292
TI  - Case 1--1999. Elective and emergency cardiac surgery on a patient with hemophilia
      B.

PMID- 10069293
TI  - Pro: All patients should receive pharmacologic prophylaxis for atrial
      fibrillation after cardiac surgery.
AB  - In addition to the physiologic manifestations of atrial fibrillation (stroke,
      ventricular arrhythmia), patients with postoperative arrhythmias have subjective
      concerns because of symptoms (palpitations), and prolonged length of stay and
      hospital cost are significant sources of visceral morbidity to both patients and
      their physicians. Efforts to terminate this arrhythmia after its initiation are
      fraught with problems ranging from ineffectiveness to toxicity. Fortunately, a
      variety of pharmacologic strategies are now available to prevent atrial
      fibrillation after cardiac surgery. At a minimum, low-dose postoperative beta
      adrenergic blockade is valuable for patients who receive these medications
      preoperatively and may be beneficial in all patients. Moreover, emerging data
      suggest that prophylaxis with antiarrhythmic compounds can significantly decrease
      the incidence of atrial fibrillation, length of hospital stay, and cost. Future
      trials will be focused on evaluating the risks and benefits of the newer
      prophylactic therapies and defining which subpopulations benefit most from such
      therapy.

PMID- 10069294
TI  - Con: All patients should not receive pharmacologic prophylaxis for atrial
      fibrillation after cardiac surgery.

PMID- 10069295
TI  - Cardiac arrest after uncomplicated right upper lobectomy.

PMID- 10069296
TI  - Early extubation after abdominal aortic reconstruction.

PMID- 10069297
TI  - The art of communication during port-access cardiac surgery procedures.

PMID- 10069298
TI  - When the transesophageal echo probe goes into the trachea.

PMID- 10069299
TI  - Transesophageal echocardiography in MIDCAB: pitfalls.

PMID- 10069300
TI  - Dilator-associated complications of central vein catheter insertion.

PMID- 10069301
TI  - Medication errors in a pediatric emergency department.
AB  - OBJECTIVE: To initiate investigation into the medication errors that occur in a
      pediatric emergency department. These errors have the potential for significant
      morbidity and mortality, as well as costly litigation. METHODS: We conducted a
      retrospective chart review of all medication and intravenous fluid errors
      identified in a pediatric emergency department through incident reports filed
      over a 5-year period. An attempt was made to determine who was involved with the
      errors and what caused the errors. The patient outcomes were noted and classified
      according to clinical significance using previously published criteria. RESULTS:
      Thirty-three incident reports involving medication or intravenous fluid errors
      were analyzed. Most errors occurred on the evening and night shifts. Nurses were
      involved in 39% of reported errors; the nurse and emergency physician were
      jointly involved in 36%. The most common error was an incorrect dose of
      medication (35%) or incorrect medication given (30%). In one third of the cases,
      the family was not made aware of the error. In 12%, patients required additional
      treatment, and one was admitted to the hospital because of the error. There were
      no deaths. CONCLUSION: Incorrect recording of patient weights leading to an
      incorrect medication dose and failure to note drug allergy are common causes for
      medication errors in the pediatric emergency department. Incorrect drugs and i.v.
      fluids are given because of similar names and packaging. Many of the errors in
      the ED seem to be preventable.

PMID- 10069302
TI  - Short vertical falls in infants.
AB  - OBJECTIVE: To define injuries from short vertical falls (SVF) in infants, and to
      compare those with minor or no injuries to those with significant injury. DESIGN:
      Descriptive, retrospective chart review. SETTING: Pediatric emergency department
      (PED) of an urban teaching hospital. SUBJECTS: Infants < or = 10 months treated
      between January 1990 and December 1992 presenting with a SVF (< or = 4 feet).
      RESULTS: 167 patients met the definition. The mean age was 5.2 months; 56% were
      male. The mechanisms of injury included rolling off a bed (55%), being dropped
      from a caretaker's arms (20%), rolling off a couch (16%), and falling from other
      objects (10%). The majority of patients (85 %) had minor or no injury.
      Significant injuries were sustained by 15% (n = 25), including 16 with a closed
      head injury (12 with skull fractures), two with intracranial bleed, and seven
      with a long bone fracture. Subsequently, the two patients with intracranial
      hemorrhages were confirmed as being from child abuse. After excluding cases of
      suspected abuse, the only characteristic found to be independently associated
      with significant injury was being dropped by the caretaker (odds ratio: 6.4 vs
      rolling or falling from furniture, 95% CI: 2.0, 21.5). CONCLUSION: The most
      common mechanism of a SVF was rolling off a bed. Most patients sustained minor or
      no injury. No child sustained an intracranial hemorrhage from a SVF. The child
      with intracranial injury and/or multiple injuries warrants an investigation.
      Being dropped appears to be a greater risk for significant injury than rolling
      off or falling from furniture.

PMID- 10069303
TI  - Incidence of bacteremia, urinary tract infections, and unsuspected bacterial
      meningitis in children with febrile seizures.
AB  - PURPOSE: To determine the incidence of bacteremia, urinary tract infections, and
      unsuspected bacterial meningitis in a cohort of children diagnosed with febrile
      seizures. METHODS: We assembled a retrospective, consecutive case series of
      patients who presented to an urban tertiary care pediatric emergency department
      for evaluation of febrile seizures during a consecutive 12- month period. A
      febrile seizure was defined as a convulsion associated with a temperature > or =
      38.0 degrees C occurring in a child < or = 6 years. Children with initial
      laboratory evidence of meningoencephalitis in the emergency department (>8 white
      blood cells per milliliter of cerebrospinal fluid), known seizure disorders,
      chronic neurologic disease, or documented immunodeficiencies were excluded.
      RESULTS: There were 243 eligible patient encounters among 218 patients during the
      study period. The mean age was 1.9+/-0.96 years (range 0.3-5.9, median 1.7), and
      156 (64.2%) were male. Of the 243 encounters, 214 (88.1%) were for simple febrile
      seizures and 29 (11.9%) were for complex febrile seizures. Blood cultures were
      performed during 206/243 encounters (84.8%), and 6/206 (2.9%, 95%CI 0.6-5.2%)
      were positive, all for Streptococcus pneumoniae. All six positive cultures
      occurred among the 154 encounters in children 3 to 36 months with a temperature >
      or = 39.0 degrees C and no pretreatment with antibiotics (incidence 6/154 or
      3.9%, 95% CI 0.9-6.9%). Urine cultures were performed during 130/243 encounters
      (53.5%), and 1/130 (0.7%, 95% CI 0.0-2.2%) yielded a bacterial pathogen.
      Cerebrospinal fluid analysis was performed during 66/243 encounters (27.2%), and
      0/66 (0.0%, 95% CI 0.0-4.5%) yielded bacterial pathogens. CONCLUSIONS: Patients
      presenting for evaluation of febrile seizures are not at increased risk for
      bacteremia or urinary tract infections. Bacterial meningitis in the absence of
      initial laboratory evidence of meningoencephalitis is very uncommon in children
      diagnosed with febrile seizures.

PMID- 10069304
TI  - Lack of a regular source of care among children using a public hospital emergency
      department.
AB  - OBJECTIVES: This study examined risk factors for not having a regular source of
      care among children presenting to an urban public hospital for nonappointment
      care. Lack of a regular source of care is associated with decreased use of
      appropriate health care services and preventive care among children. METHODS: A
      cross-sectional survey was conducted for all children less than 16 years of age
      attending an emergency department at an urban public hospital over a consecutive
      7-day period. Univariate and multivariate logistic regression analyses were
      conducted. RESULTS: In 791 interviews available for analysis, 52% of preschool
      children and 66% of school-aged children did not have a regular source of care.
      Children without a regular source of care were more likely to present for
      nonurgent conditions (P < 0.0005). In multivariate analysis, older age of the
      child (OR = 1.6, 95% CI 1.132.25), lack of insurance (OR = 1.47, 95% CI 1.03
      2.11), and lack of personal vehicle (OR = 1.44, 95% CI 1.05-1.97) were associated
      with not having a regular source of care. CONCLUSIONS: The majority of children
      using an urban emergency department were without a regular source of care. In
      this population, no single factor identified children without a regular source of
      care, but increased age and lack of insurance were associated with it. Addressing
      this situation will require a multifaceted approach that includes, but is not
      limited to, decreasing financial barriers.

PMID- 10069305
TI  - Doctors, nurses, and parents are equally poor at estimating pediatric weights.
AB  - OBJECTIVE: To evaluate the relative accuracy of physicians, nurses, and parents
      in estimating the weight of children presenting to the emergency department.
      METHODS: One hundred pediatric patients between the ages of 0 and 8 years
      presenting to an urban teaching emergency department (40,000 patients per year)
      were enrolled over a 1-month period (September 1996). The parents, triage nurse,
      and examining physician were asked to estimate the patient's weight, each blinded
      to the others' estimates and the child's actual weight. RESULTS: Parents, nurses,
      and physicians all slightly underestimated patient weights (P < 0 .05), but these
      groups did not differ among themselves (P > 0 .05). The total range of estimates
      was broad in each group (parents +292% to -41%, nurses +30% to -36%, and
      physicians +43% to -56%). There was no significant relationship between estimates
      with regard to age, weight, or sex. Twenty-nine percent of physicians' estimates,
      40% of nurses' estimates, and 16% of parents' estimates differed from the actual
      weight by more than 15%. CONCLUSION: Emergency department pediatric weight
      estimates by parents, nurses, and physicians are significantly and similarly
      unreliable.

PMID- 10069306
TI  - Parental estimates of their child's weight: accurate for resuscitation drug
      doses.
AB  - OBJECTIVE: The aim of this study was to assess parental reliability in estimating
      child body weight in emergency situations, when weighing the child is often
      impossible. METHODS: 312 parents were asked to complete an anonymous
      questionnaire that included estimating their child's weight. 233 questionnaires
      were enrolled in the study and were assessed statistically using Students t test,
      and chi2 and ANOVA tests. RESULTS: 51.5% of parents estimated their child's body
      weight within +/-5% of the true weight, 73.4% within +/-10%, and 87.5% within +/
      20%. A significant difference was found between paternal and maternal
      estimations, with 56% of mothers and only 40.3% of fathers estimating within a 5%
      range of accuracy (P < 0.05). CONCLUSIONS: Parents, especially mothers, can
      estimate their child's body weight within clinically acceptable limits. These
      estimations can reliably be used to calculate drug doses in prehospital and
      emergency department situations, when children's weight is not known and cannot
      be measured.

PMID- 10069307
TI  - Delayed presentation of traumatic arterial vasospasm.
AB  - Traumatic arterial vasospasm with no surrounding anatomic damage is a rare
      finding. Delayed presentation of arterial vasospasm several days from the
      inciting event is also rare. However, when the diagnosis of arterial vasospasm is
      considered, evaluation and treatment must be initiated promptly to avoid
      prolonged ischemia to the extremity. We present an 11-year-old female who
      presented with a delayed presentation of arterial vasospasm, and also review the
      literature.

PMID- 10069308
TI  - Atlantoaxial rotary subluxation in children.
AB  - Traumatic torticollis is an uncommon complaint in the emergency department (ED).
      One important cause in children is atlantoaxial rotary subluxation. Most children
      present with pain, torticollis ("cock-robin" position), and diminished range of
      motion. The onset is spontaneous and usually occurs following minor trauma. A
      thorough history and physical examination will eliminate the various causes of
      torticollis. Radiographic evaluation will demonstrate persistent asymmetry of the
      odontoid in its relationship to the atlas. Computed tomography, especially a
      dynamic study, may be needed to verify the subluxation. Treatment varies with
      severity and duration of the abnormality. For minor and acute cases, a soft
      cervical collar, rest, and analgesics may be sufficient. For more severe cases,
      the child may be placed on head halter traction, and for long-standing cases,
      halo traction or even surgical interventions may be indicated. We describe two
      patients with atlantoaxial rotary subluxation, who presented with torticollis, to
      illustrate recognition and management in the ED.

PMID- 10069309
TI  - Emergency cardiopulmonary bypass for cardiac arrest refractory to pediatric
      advanced life support.
AB  - We report the application of emergent cardiopulmonary bypass (CPB) for three
      pediatric patients in the cardiac catheterization laboratory with cardiac arrest
      who did not respond to conventional resuscitation efforts. All three patients had
      return of baseline prearrest rhythms within minutes of the initiation of
      artificial cardiopulmonary support and the return of spontaneous circulation upon
      weaning CPB. Two patients had normal neurologic outcomes despite an interval of
      over 30 minutes from arrest to CPB. The continued judicious application and study
      of this technology in a small subpopulation of pediatric cardiac arrest patients
      is warranted.

PMID- 10069310
TI  - Caterpillars: an unusual source of ingestion.
AB  - PURPOSE: To describe a series of patients seen in a pediatric emergency
      department with adverse effects following an ingestion of a caterpillar. METHODS:
      Case series. RESULTS: Ten patients presented to the emergency department
      following ingestion of a caterpillar. Adverse effects ranged from drooling and
      refusal to drink to diffuse urticaria. Six patients were admitted and five
      underwent direct laryngoscopy and bronchoscopy in the operating room. None of the
      10 patients had an adverse outcome. CONCLUSIONS: Previously not described,
      significant adverse effects can occur following ingestion of a caterpillar. In
      addition, although not previously reported, the caterpillar of the Hickory
      Tussock moth can cause adverse effects in humans.

PMID- 10069311
TI  - Recognition and management of Tillaux fractures in adolescents.
AB  - Tillaux fractures are relatively uncommon Salter Harris III fractures of the
      tibia. The importance of recognizing this fracture is that a residual deformity
      in the joint surface can lead to premature degenerative arthritis. For this
      reason, it is important that accurate imaging to assess the congruity of the
      joint, as well as adequate reduction, is obtained. These fractures can occur in
      adolescents in the 18-month period during which the distal tibial epiphysis is
      closing. These injuries occur either by lateral rotation of the foot or by medial
      rotation of the leg on the fixed foot. Closed reduction is sufficient in most
      cases; however, if a gap of > or = 2 mm of the articular surface remains, open
      reduction is usually required to adequately reduce the articular surface.
      Orthopedic injuries are one of the most common reasons children are brought to
      the emergency department (ED). Most of these injuries are easily managed by
      splinting, with outpatient orthopedic follow-up. However, certain fractures need
      closer evaluation and immediate consultation with an orthopedic surgeon. One
      relatively uncommon fracture that needs special attention is the Tillaux
      fracture. Paul Jules Tillaux first described this particular fracture in 1892. He
      performed experiments on cadavers and found that stress to the anterior inferior
      tibiofibular ligament could lead to this type of avulsion fracture, which today
      is termed the Tillaux fracture. The distal tibial epiphysis is involved, and the
      mechanism usually is forced external rotation of the foot in a 12- to 14-year-old
      adolescent. This fracture only occurs during a certain time of adolescence, owing
      to the differential growth rate of the epiphysis, and only under certain
      circumstances. The fracture is of great importance because it involves a major
      weight-bearing articular surface. A residual deformity of the joint surface can
      lead to premature degenerative arthritis. We present a patient with a Tillaux
      fracture to elaborate on the mechanism of injury and to summarize the importance
      of its recognition and imaging and treatment options.

PMID- 10069312
TI  - Etiology of septic arthritis in children: an update for the 1990s.
AB  - OBJECTIVE: To establish the etiology of septic arthritis in children after
      implementation of HIB immunization guidelines. METHODS: A retrospective review of
      all charts with a discharge diagnosis of septic arthritis (ICD-9: 711) from
      January 1991 to December 1996 at St. Louis Children's Hospital was conducted.
      RESULTS: Sixty-four patients (male = 58%) were identified, whose median age was
      6.0 years. Twenty-one children (33%) were misdiagnosed on initial presentation.
      An organism was isolated in 38 (59%) of cases. The predominant organisms were
      Staphylococcus aureus (10 isolates), Group A Streptococcus (4), Enterobacter
      species (4), Kingella kingae (3), Neisseria meningitides (3), Streptococcus
      pneumoniae (2), Neisseria gonorrhoeae (2), Candida (2), Staphylococcus
      epidermidis (2). The only isolate of Haemophilus influenzae type B was in 1992 in
      an unimmunized 14 month old. CONCLUSIONS: These data confirm Staphylococcus
      aureus as a frequent pathogen and suggest that H influenzae type B is no longer
      the predominant isolate in young children with septic arthritis. In addition,
      early septic arthritis in children is frequently misdiagnosed on initial
      evaluation.

PMID- 10069313
TI  - "The silent killer": chronic acetaminophen toxicity in a toddler.
AB  - We report a case fatality from chronic acetaminophen (APAP) toxicity in an 18
      month-old toddler, born 14 weeks premature, who had been receiving less than the
      standard toxic threshold of the pediatric suspension of APAP for 4 days prior to
      presentation. Furthermore, he had been on prolonged total parenteral nutrition
      (TPN) as an infant. We hypothesize that TPN-induced hepatic changes may have
      diminished the patient's hepatic reserve, making him more susceptible to APAP
      toxicity. We propose that different "therapeutic" APAP dosing may be needed for
      those with underlying risk factors for hepatotoxicity.

PMID- 10069314
TI  - Autoerythrocyte sensitization (psychogenic purpura): a case report and review of
      the literature.
AB  - Autoerythrocyte sensitization (psychogenic purpura) is an unusual diagnosis, but
      one that has a characteristic dermatologic manifestation of painful bruising. A
      typical case is presented, as well as a review of the literature. Treatment
      consists of psychiatric therapy, which is most effective when initiated early in
      the disease, so early diagnosis will not only minimize the cost of the medical
      evaluation but will also benefit the patient.

PMID- 10069315
TI  - Acute care of the child with a tracheostomy.

PMID- 10069316
TI  - Priorities for research in emergency medical services for children: results of a
      consensus conference.
AB  - 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 I 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 II of the study involved a meeting of the panel,
      where the results of Round I were discussed and the topics were 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; 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 research agenda for
      such services.

PMID- 10069317
TI  - Flunitrazepam: a review of "roofies".

PMID- 10069318
TI  - Pediatric emergency medicine: legal briefs.

PMID- 10069319
TI  - Capnography in the pediatric emergency department.

PMID- 10069320
TI  - Abdominal pain, vomiting, and diarrhea.

PMID- 10069321
TI  - Vancomycin use.

PMID- 10069322
TI  - The GDNF protein family: gene ablation studies reveal what they really do and
      how.

PMID- 10069323
TI  - Drosophila odor receptors revealed.

PMID- 10069324
TI  - A sweet beginning.

PMID- 10069325
TI  - Variable loudness at individual excitatory synapses.

PMID- 10069326
TI  - A taste for development.

PMID- 10069327
TI  - From channels to behavior: an integrative model of NaCl taste.

PMID- 10069328
TI  - Ion channel defects in hereditary hearing loss.

PMID- 10069329
TI  - From lesions to leptin: hypothalamic control of food intake and body weight.

PMID- 10069330
TI  - Relating hippocampal circuitry to function: recall of memory sequences by
      reciprocal dentate-CA3 interactions.

PMID- 10069331
TI  - Retarded growth and deficits in the enteric and parasympathetic nervous system in
      mice lacking GFR alpha2, a functional neurturin receptor.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and a related protein,
      neurturin (NTN), require a GPI-linked coreceptor, either GFR alpha1 or GFR
      alpha2, for signaling via the transmembrane Ret tyrosine kinase. We show that
      mice lacking functional GFR alpha2 coreceptor (Gfra2-/-) are viable and fertile
      but have dry eyes and grow poorly after weaning, presumably due to malnutrition.
      While the sympathetic innervation appeared normal, the parasympathetic
      cholinergic innervation was almost absent in the lacrimal and salivary glands and
      severely reduced in the small bowel. Neurite outgrowth and trophic effects of NTN
      at low concentrations were lacking in Gfra2-/- trigeminal neurons in vitro,
      whereas responses to GDNF were similar between the genotypes. Thus, GFR alpha2 is
      a physiological NTN receptor, essential for the development of specific
      postganglionic parasympathetic neurons.

PMID- 10069332
TI  - Gene targeting reveals a critical role for neurturin in the development and
      maintenance of enteric, sensory, and parasympathetic neurons.
AB  - Neurturin (NTN) is a neuronal survival factor that activates the Ret tyrosine
      kinase in the presence of a GPI-linked coreceptor (either GFR alpha1 or GFR
      alpha2). Neurturin-deficient (NTN-/-) mice generated by homologous recombination
      are viable and fertile but have defects in the enteric nervous system, including
      reduced myenteric plexus innervation density and reduced gastrointestinal
      motility. Parasympathetic innervation of the lacrimal and submandibular salivary
      gland is dramatically reduced in NTN-/- mice, indicating that Neurturin is a
      neurotrophic factor for parasympathetic neurons. GFR alpha2-expressing cells in
      the trigeminal and dorsal root ganglia are also depleted in NTN-/- mice. The loss
      of GFR alpha2-expressing neurons, in conjunction with earlier studies, provides
      strong support for GFR alpha2/Ret receptor complexes as the critical mediators of
      NTN function in vivo.

PMID- 10069333
TI  - Engrailed negatively regulates the expression of cell adhesion molecules
      connectin and neuroglian in embryonic Drosophila nervous system.
AB  - Engrailed is expressed in subsets of interneurons that do not express Connectin
      or appreciable Neuroglian, whereas other neurons that are Engrailed negative
      strongly express these adhesion molecules. Connectin and Neuroglian expression
      are virtually eliminated in interneurons when engrailed expression is driven
      ubiquitously in neurons, and greatly increased when engrailed genes are lacking
      in mutant embryos. The data suggest that Engrailed is normally a negative
      regulator of Connectin and neuroglian. These are the first two "effector" genes
      identified in the nervous system of Drosophila as regulatory targets for
      Engrailed. We argue that differential Engrailed expression is crucial in
      determining the pattern of expression of cell adhesion molecules and thus
      constitutes an important determinant of neuronal shape and perhaps connectivity.

PMID- 10069334
TI  - Distinct functions of alpha3 and alpha(v) integrin receptors in neuronal
      migration and laminar organization of the cerebral cortex.
AB  - Changes in specific cell-cell recognition and adhesion interactions between
      neurons and radial glial cells regulate neuronal migration as well as the
      establishment of distinct layers in the developing cerebral cortex. Here, we show
      that alpha3beta1 integrin is necessary for neuron-glial recognition during
      neuronal migration and that alpha(v) integrins provide optimal levels of the
      basic neuron-glial adhesion needed to maintain neuronal migration on radial glial
      fibers. A gliophilic-to-neurophilic switch in the adhesive preference of
      developing cortical neurons occurs following the loss of alpha3beta1 integrin
      function. Furthermore, the targeted mutation of the alpha3 integrin gene results
      in abnormal layering of the cerebral cortex. These results suggest that
      alpha3beta1 and alpha(v) integrins regulate distinct aspects of neuronal
      migration and neuron-glial interactions during corticogenesis.

PMID- 10069335
TI  - Profilin and the Abl tyrosine kinase are required for motor axon outgrowth in the
      Drosophila embryo.
AB  - The ability of neuronal growth cones to be guided by extracellular cues requires
      intimate communication between signal transduction systems and the dynamic actin
      based cytoskeleton at the leading edge. Profilin, a small, actin-binding protein,
      has been proposed to be a regulator of the cell motility machinery at leading
      edge membranes. However, its requirement in the developing nervous system has
      been unknown. Profilin associates with members of the Enabled family of proteins,
      suggesting that Profilin might link Abl function to the cytoskeleton. Here,
      genetic analysis in Drosophila is used to demonstrate that mutations in Profilin
      (chickadee) and Abl (abl) display an identical growth cone arrest phenotype for
      axons of intersegmental nerve b (ISNb). Moreover, the phenotype of a double
      mutant suggests that these components function together to control axonal
      outgrowth.

PMID- 10069336
TI  - The tyrosine kinase Abl and its substrate enabled collaborate with the receptor
      phosphatase Dlar to control motor axon guidance.
AB  - Genetic analysis of growth cone guidance choice points in Drosophila identified
      neuronal receptor protein tyrosine phosphatases (RPTPs) as key determinants of
      axon pathfinding behavior. We now demonstrate that the Drosophila Abl tyrosine
      kinase functions in the intersegmental nerve b (ISNb) motor choice point pathway
      as an antagonist of the RPTP Dlar. The function of Abl in this pathway is
      dependent on an intact catalytic domain. We also show that the Abl phosphoprotein
      substrate Enabled (Ena) is required for choice point navigation. Both Abl and Ena
      proteins associate with the Dlar cytoplasmic domain and serve as substrates for
      Dlar in vitro, suggesting that they play a direct role in the Dlar pathway. These
      data suggest that Dlar, Abl, and Ena define a phosphorylation state-dependent
      switch that controls growth cone behavior by transmitting signals at the cell
      surface to the actin cytoskeleton.

PMID- 10069337
TI  - Mena is required for neurulation and commissure formation.
AB  - Mammalian enabled (Mena) is a member of a protein family thought to link signal
      transduction pathways to localized remodeling of the actin cytoskeleton. Mena
      binds directly to Profilin, an actin-binding protein that modulates actin
      polymerization. In primary neurons, Mena is concentrated at the tips of growth
      cone filopodia. Mena-deficient mice are viable; however, axons projecting from
      interhemispheric cortico-cortical neurons are misrouted in early neonates, and
      failed decussation of the corpus callosum as well as defects in the hippocampal
      commissure and the pontocerebellar pathway are evident in the adult. Mena
      deficient mice that are heterozygous for a Profilin I deletion die in utero and
      display defects in neurulation, demonstrating an important functional role for
      Mena in regulation of the actin cytoskeleton.

PMID- 10069338
TI  - A novel family of divergent seven-transmembrane proteins: candidate odorant
      receptors in Drosophila.
AB  - Although insects have proven to be valuable models for exploring the function,
      organization, and development of the olfactory system, the receptor molecules
      that bind odors have not been identified in any insect. We have developed a novel
      search algorithm, used it to search the Drosophila genomic sequence database, and
      identified a large multigene family encoding seven transmembrane domain proteins
      that are expressed in olfactory organs. We show that expression is restricted to
      subsets of olfactory receptor neurons (ORNs) for a number of these genes.
      Different members of the family initiate expression at different times during
      antennal development. Some of the genes are not expressed in a mutant of the Acj6
      POU-domain transcription factor, a mutant in which a subset of ORNs show abnormal
      odorant specificities.

PMID- 10069339
TI  - The odor specificities of a subset of olfactory receptor neurons are governed by
      Acj6, a POU-domain transcription factor.
AB  - Little is known about how the odor specificities of olfactory neurons are
      generated, a process essential to olfactory coding. We have found that neuronal
      identity relies on the abnormal chemosensory jump 6 (acj6) gene, originally
      identified by a defect in olfactory behavior. Physiological analysis of
      individual olfactory neurons shows that in acj6 mutants, a subset of neurons
      acquires a different odorant response profile. Certain other neurons do not
      respond to any tested odors in acj6. Molecular analysis of acj6 shows that it
      encodes a POU-domain transcription factor expressed in olfactory neurons. Our
      data suggest that the odor response spectrum of an olfactory neuron, and perhaps
      the choice of receptor genes, is determined through a process requiring the
      action of Acj6.

PMID- 10069340
TI  - Crossmodal associative memory representations in rodent orbitofrontal cortex.
AB  - Firing patterns of neurons in the orbitofrontal cortex (OF) were analyzed in rats
      trained to perform a task that encouraged incidental associations between
      distinct odors and the places where their occurrence was detected. Many of the
      neurons fired differentially when the animals were at a particular location or
      sampled particular odors. Furthermore, a substantial fraction of the cells
      exhibited odor-specific firing patterns prior to odor presentation, when the
      animal arrived at a location associated with that odor. These findings suggest
      that neurons in the OF encode cross-modal associations between odors and
      locations within long-term memory.

PMID- 10069341
TI  - Synchronous membrane potential fluctuations in neurons of the cat visual cortex.
AB  - We have recorded intracellularly from pairs of neurons less than 500 microm
      distant from one another in V1 of anesthetized cats. Cross-correlation of
      spontaneous fluctuations in membrane potential revealed significant correlations
      between the cells in each pair. This synchronization was not dependent on the
      occurrence of action potentials, indicating that it was not caused by mutual
      interconnections. The cells were synchronized continuously rather than for brief
      epochs. Much weaker correlations were found between the EEG and intracellular
      potentials, suggesting local, rather than global, synchrony. The highest
      correlation occurred among cells with similar connectivity from the LGN and
      similar receptive fields. During visual stimulation, correlations increased when
      both cells responded to the stimulus and decreased when neither cell responded.

PMID- 10069342
TI  - Selective pruning of more active afferents when cat visual cortex is
      pharmacologically inhibited.
AB  - Activity-dependent competition is thought to guide the normal development of
      specific patterns of neural connections. Such competition generally favors more
      active inputs, making them larger and stronger, while less active inputs become
      smaller and weaker. We pharmacologically inhibited the activity of visual
      cortical cells and measured the three-dimensional structure of inputs serving the
      two eyes when one eye was occluded. The more active inputs serving the open eye
      actually became smaller than the deprived inputs from the occluded eye, which
      were similar to those in normal animals. These findings demonstrate in vivo that
      it is not the amount of afferent activity but the correlation between cortical
      and afferent activity that regulates the growth or retraction of these inputs.

PMID- 10069343
TI  - Linear summation of excitatory inputs by CA1 pyramidal neurons.
AB  - A fundamental problem in neurobiology is understanding the arithmetic that
      dendrites use to integrate inputs. The impact of dendritic morphology and active
      conductances on input summation is still unknown. To study this, we use glutamate
      iontophoresis and synaptic stimulation to position pairs of excitatory inputs
      throughout the apical, oblique, and basal dendrites of CA1 pyramidal neurons in
      rat hippocampal slices. Under a variety of stimulation regimes, we find a linear
      summation of most input combinations that is implemented by a surprising balance
      of boosting and shunting mechanisms. Active conductances in dendrites
      paradoxically serve to make summation linear. This "active linearity" can
      reconcile predictions from cable theory with the observed linear summation in
      vivo and suggests that a simple arithmetic is used by apparently complex
      dendritic trees.

PMID- 10069344
TI  - Variability of neurotransmitter concentration and nonsaturation of postsynaptic
      AMPA receptors at synapses in hippocampal cultures and slices.
AB  - To understand the elementary unit of synaptic communication between CNS neurons,
      one must know what causes the variability of quantal postsynaptic currents and
      whether unitary packets of transmitter saturate postsynaptic receptors. We
      studied single excitatory synapses between hippocampal neurons in culture. Focal
      glutamate application at individual postsynaptic sites evoked currents (I(glu))
      with little variability compared with quantal excitatory postsynaptic currents
      (EPSCs). The maximal I(glu) was >2-fold larger than the median EPSC. Thus,
      variations in [glu]cleft are the main source of variability in EPSC size, and
      glutamate receptors are generally far from saturation during quantal
      transmission. This conclusion was verified by molecular antagonism experiments in
      hippocampal cultures and slices. The general lack of glutamate receptor
      saturation leaves room for increases in [glu]cleft as a mechanism for synaptic
      plasticity.

PMID- 10069345
TI  - First Mayo Clinic Hospital opens.

PMID- 10069346
TI  - Increasing the proportion of women in academic medicine: one institution's
      response.
AB  - OBJECTIVE: To increase gender diversity among the physician consulting staff
      (PCS) at a major medical center. DESIGN: Because the proportion of female PCS at
      academic medical centers in the United States has not increased commensurately
      with increases in the proportion of female graduates from American medical
      schools, a modeling and graphing technique was developed to analyze this problem
      and recommend solutions for one large academic medical center. MATERIAL AND
      METHODS: Personnel data, by gender and year from 1980 through 1994, were
      collected for all PCS at Mayo Clinic Rochester (MCR). These data were compared
      with similar data from other US academic medical centers and were used to develop
      models to predict the proportion of female PCS at MCR yearly until 2005, assuming
      various hiring and resignation patterns. Novel techniques were developed to
      illustrate and compare the models. Model-based predictions were compared with
      national projections, and a realistic target proportion of female PCS was defined
      on the basis of assumptions about the proportion of female graduates from medical
      school and internship programs during the next 10 years as well as probable
      hiring, retention, and resignation rates at MCR. To identify issues critical to
      recruitment, retention, and professional growth of female PCS at MCR, we used
      factor analysis to assess responses to a confidential questionnaire sent to all
      female faculty members. RESULTS: In 1994 and 1995, the proportion of female PCS
      was 25% at US academic medical centers but only 15% at MCR, and the rate at which
      this proportion increased from 1980 through 1994 at MCR was also lower than the
      national rate. Model-based predictions demonstrated that gradually (1.5% per
      year) increasing the female percentage of new recruits from 26% in 1995 to 40% in
      2005 would achieve the targeted 25% female PCS in 13 years. Questionnaire
      responses from 119 (68%) of the 175 female PCS at MCR identified 6 important
      recommendations for recruitment and retention of female PCS: survey resignees and
      candidates who decline positions; appoint more qualified women to policy-making
      committees; require sensitivity and diversity training for all staff (especially
      leaders); develop explicit, gender-sensitive criteria for selecting department
      and division chairs; compare Mayo gender and diversity data with national data at
      the department or division level; and develop mechanisms for mentoring junior
      female staff members. CONCLUSION: We developed useful methods for analyzing the
      PCS gender distribution, defined feasible hiring strategies, and identified
      specific recommendations to enhance the professional experience of female PCS.
      These methods can provide a model for other institutions seeking to optimize
      gender diversity among their staff.

PMID- 10069347
TI  - Postmortem analysis of encapsulation around long-term ventricular endocardial
      pacing leads.
AB  - OBJECTIVE: To analyze the site and thickness of encapsulation around ventricular
      endocardial pacing leads and the extent of tricuspid valve adhesion, from today's
      perspective, with implications for lead removal and sensor location. MATERIAL AND
      METHODS: Gross cardiac postmortem analysis was performed in 11 cases (8 female
      and 3 male patients; mean age, 78+/-7 years). None of the patients had died
      because of pacemaker malfunction. The mean implant time was 61+/-60 months
      (range, 4 to 184). RESULTS: The observations ranged from encapsulation only at
      the tip of the pacing lead to complete encapsulation along the entire length of
      the pacing lead within the right ventricle. Substantial areas of adhesion at the
      tricuspid valve apparatus were noted in 7 of the 11 cases (64%). The firmly
      attached leads could be removed only by dissection, and in some cases, removal
      was possible only by damaging the associated structures. No specific optimal site
      for sensor placement could be identified along the ventricular portion of the
      pacing leads; however, the fibrotic response was relatively less prominent in the
      atrial chamber. CONCLUSION: Extensive encapsulation is present in most long-term
      pacemaker leads, which may complicate lead removal. The site and thickness of
      encapsulation seem to be highly variable. Tricuspid valve adhesion, which is
      usually underestimated, may be severe. In contrast to earlier reports, our study
      demonstrates that the extent of fibrotic encapsulation may not be related to the
      duration since lead implantation. Moreover, we noted no ideal encapsulation-free
      site for sensors on the ventricular portion of long-term pacing leads.

PMID- 10069348
TI  - Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma
      and its increase during human heart failure.
AB  - OBJECTIVE: To determine whether Dendroaspis natriuretic peptide (DNP), a novel
      peptide isolated from the venom of the Dendroaspis angusticeps snake that
      contains a 17-amino acid disulfide ring structure similar to that in atrial,
      brain, and C-type natriuretic peptides, is present in normal human plasma and
      myocardium and whether, like the other natriuretic peptides, DNP-like
      immunoreactivity (DNP-LI) is activated in human congestive heart failure (CHF).
      MATERIAL AND METHODS: Circulating DNP-LI was assessed in 19 normal human subjects
      and 19 patients with CHF (New York Heart Association class III or IV) with a
      specific and sensitive radioimmunoassay for DNP with no cross-reactivity with the
      other natriuretic peptides. Immunohistochemical studies that used polyclonal
      rabbit anti-DNP antiserum were performed on human atrial myocardial tissue
      obtained from four patients with end-stage CHF who were undergoing cardiac
      transplantation and from three donor hearts at the time of transplantation.
      RESULTS: We report that DNP-LI circulates in normal human plasma and is present
      in the normal atrial myocardium. In addition, DNP-LI is increased in the plasma
      of patients with CHF. CONCLUSION: This study demonstrates, for the first time,
      the presence of a DNP-like peptide in normal human plasma and in the atrial
      myocardium. Additionally, these studies demonstrate increased plasma DNP-LI in
      human CHF. These results support the possible existence of an additional new
      natriuretic peptide in humans, which may have a role in the neurohumoral
      activation that characterizes human CHF.

PMID- 10069349
TI  - A prospective study of pathogenesis of catheter-associated urinary tract
      infections.
AB  - OBJECTIVE: To determine the pathogenesis of catheter-associated urinary tract
      infection (CAUTI) and the relative importance of each of the possible mechanisms
      of entry of infecting microorganisms to the catheterized urinary tract. MATERIAL
      AND METHODS: We conducted a prospective study of 1,497 newly catheterized
      patients. Paired quantitative urine cultures were obtained daily, from the
      catheter specimen port and from the collection bag, using a technique that could
      detect 1 colony-forming unit/mL. We assumed that with extraluminal infections,
      caused by microorganisms ascending from the perineum in the mucous film
      contiguous to the external surface of the catheter, the organisms would be
      detected first in bladder urine or in far higher concentrations in urine from the
      specimen port than from the collection bag. With intraluminal CAUTIs, caused by
      microorganisms gaining access to the catheter lumen because of failure of closed
      drainage or contamination of collection bag urine, the organisms would be
      detected first or in far larger numbers in a collection bag specimen. RESULTS:
      The probable mechanism of infection could be determined for 173 of 250 organisms
      (69.2 %) identified in 235 new-onset CAUTIs. Among these 173 cases, 115 (66%)
      were extraluminally acquired, and 58 (34%) were derived from intraluminal
      contaminants. For these determinable cases, CAUTIs caused by gram-positive cocci
      (enterococci and staphylococci) and yeasts were far more likely to be
      extraluminally acquired (extraluminal:intraluminal, 2.9) than were gram-negative
      bacilli, which caused CAUTIs by both routes equally (extraluminal: intraluminal,
      1.2; P = 0.007). Surprisingly, no significant differences were noted in
      pathogenetic mechanisms between men and women. CONCLUSION: We conclude that, in
      both men and women, CAUTIs occur by both extraluminal and intraluminal portals of
      entry but derive preponderantly from organisms that gain access extraluminally.
      Strategies for prevention of CAUTIs must focus on new technologies to prevent
      access of organisms by all possible routes.

PMID- 10069350
TI  - Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in
      patients with recurrent glioma.
AB  - OBJECTIVE: To assess the pharmacokinetics, toxicity, and efficacy of
      antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261). DESIGN: We initiated a
      phase II trial in order to determine whether evidence of antitumor activity of
      A10 and AS2-1 could be documented. MATERIAL AND METHODS: Patients with anaplastic
      astrocytoma or glioblastoma multiforme recurring after radiation therapy were
      eligible for enrollment in the trial. Patients received escalating doses of A10
      and AS2-1 by multiple intermittent intravenous injections with use of a portable
      programmable pump to the target daily dose of 1.0 g/kg for A10 and of 0.4 g/kg
      for AS2-1. RESULTS: Nine patients were treated, in six of whom the treatment
      response was assessable in accordance with protocol stipulations. No patient
      demonstrated tumor regression. Reversible grade 2 or 3 neurocortical toxicity,
      consisting of transient somnolence, confusion, and exacerbation of an underlying
      seizure disorder, was noted in five patients. Mean steady-state plasma
      concentrations of phenylacetate and phenylacetylglutamine after escalation to the
      target doses of A10 and AS2-1 were 177+/-101 microg/mL and 302+/-102 microg/mL,
      respectively. Patients who exhibited confusion tended to have higher
      phenylacetate levels. CONCLUSION: Although we could not confirm any tumor
      regression in patients in this study, the small sample size precludes definitive
      conclusions about treatment efficacy. Antineoplaston-related toxicity was
      acceptable in most patients with appropriate dose modification, although severe
      neurocortical toxicity may occur. Steady-state plasma concentrations of
      phenylacetate with use of A10 and AS2-1 were similar to those reported with use
      of similar doses of phenylacetate alone.

PMID- 10069351
TI  - Shibasaburo Kitasato--Japanese bacteriologist.

PMID- 10069352
TI  - Spinal epidural hematoma and high thromboembolic risk: between Scylla and
      Charybdis.
AB  - OBJECTIVE: To determine the optimal time for reinstitution of anticoagulant
      therapy after evacuation of spinal epidural hematoma in patients who have a high
      risk for cardiogenic embolization. MATERIAL AND METHODS: The clinical histories
      of all patients with a spinal epidural hematoma encountered at Mayo Clinic
      Rochester between 1975 and 1996 were reviewed. We present three cases of
      spontaneous spinal epidural hematoma and the management of anticoagulation in
      each case. RESULTS: Of the 17 patients identified, 3 received anticoagulant
      therapy at the onset of the hematoma and were at high risk for cardiogenic
      embolization. In two patients with a metallic heart valve and one patient with
      long-standing atrial fibrillation, anticoagulant therapy was discontinued for 5,
      13, and 18 days, respectively, after decompressive laminectomy. Systemic
      embolization occurred in one patient with a previous history of embolization to
      the femoral artery. No systemic embolization occurred in the two patients with a
      metallic valve. CONCLUSION: Early resumption of warfarin therapy is indicated
      after a spinal surgical procedure; however, discontinuation of anticoagulation
      for several days seems safe while postoperative hemostasis is monitored.

PMID- 10069353
TI  - Histologically proven lymphocytic hypophysitis: spontaneous resolution and
      subsequent pregnancy.
AB  - Of the 128 previously reported cases of lymphocytic hypophysitis, the diagnosis
      was histologically proven in 6 patients in whom the pituitary mass regressed
      spontaneously; only 1 subsequently became pregnant. Among six additional patients
      who became pregnant after a diagnosis of presumed lymphocytic hypophysitis, the
      disease was confirmed histologically in only three, two of whom underwent
      surgical debulking and one who had no follow-up imaging. To our knowledge, we
      describe the second patient with histologically proven lymphocytic hypophysitis,
      associated with adrenocorticotropic hormone (corticotropin) and prolactin
      deficiencies, in whom the pituitary mass regressed completely with physiologic
      hydrocortisone therapy only and in whom a spontaneous pregnancy occurred
      subsequently with no postpartum recurrence of the pituitary mass. This
      information lends credence to previous recommendations that, in the absence of
      visual field defects, surgical and corticosteroid therapy may be safely withheld,
      with periodic reassessment.

PMID- 10069354
TI  - Successful treatment of obstructive sleep apnea with use of nasal continuous
      positive airway pressure in three patients with mucosal hemangiomas of the oral
      cavity.
AB  - Cysts and benign tumors are uncommon causes of obstructive sleep apnea (OSA), and
      surgical removal is usually favored. In patients in whom an operation poses a
      high risk, however, nasal continuous positive airway pressure (CPAP) may prove
      beneficial. We describe three patients with hemangiomas of the oral cavity in
      whom polysomnography revealed moderate to severe OSA. In all three patients,
      nasal CPAP effectively decreased sleep-related disordered breathing events and
      dramatically improved their sleep. To our knowledge, this is the first report of
      OSA associated with hemangiomas involving the upper airway. Our experience
      suggests that nasal CPAP therapy is effective and well tolerated in such
      patients.

PMID- 10069355
TI  - Diagnosing polycythemia vera: a paradigm shift.
AB  - The primary objective during the evaluation of erythrocytosis is to ascertain the
      presence or absence of polycythemia vera (PV). Because of prognostic and
      treatment differences, PV must be distinguished from relative polycythemia and
      secondary erythrocytosis. This distinction is currently accomplished through the
      laboratory measurement of red blood cell mass, plasma volume, and arterial oxygen
      saturation and determination of oxygen pressure at 50% hemoglobin saturation
      (P50). Furthermore, according to the Polycythemia Vera Study Group guidelines,
      the demonstration of an increased red blood cell mass is an absolute criterion
      for the diagnosis of PV. This article discusses the use of the serum
      erythropoietin level and endogenous erythroid colony assay as a potential
      alternative in the diagnosis of PV.

PMID- 10069356
TI  - Human herpesvirus 6.
AB  - Human herpesvirus (HHV) 6 is a beta-herpes, DNA virus. This virus shows closest
      homology with cytomegalovirus and HHV-7. Infection usually occurs in infants 6 to
      24 months of age, and primary infection may result in roseola. HHV-6 infection in
      infants is the commonest cause of fever-induced seizures. Infection in adults is
      seen primarily in immunocompromised hosts with solid organ transplants or in
      those with human immunodeficiency virus infection. The virus is capable of
      pronounced interaction in vitro with cytomegalovirus and human immunodeficiency
      virus and induces immunosuppression and apoptosis. The importance of these
      interactions in vivo necessitates further investigation. HHV-6 infection may
      contribute to the pathogenesis of multiple sclerosis. HHV-6 may be diagnosed by
      viral culture, serology, or polymerase chain reaction.

PMID- 10069357
TI  - Improving the adverse cardiovascular prognosis of type 2 diabetes.
AB  - Approximately 80% of all patients with diabetes die of cardiovascular disease.
      The traditional management of type 2 diabetes has been ineffective in altering
      this dismal prognosis. Insulin resistance is the fundamental defect of type 2
      diabetes. Insulin resistance often leads to hyperinsulinemia, which is associated
      with hypertension, atherogenic dyslipidemia, left ventricular hypertrophy,
      impaired fibrinolysis, visceral obesity, and sedentary lifestyle. Although all
      these conditions are associated with atherosclerosis and adverse cardiovascular
      events, the therapeutic efforts in patients with diabetes have focused
      predominantly on normalizing glucose levels. Improved insulin sensitivity through
      lifestyle modifications or pharmacologic therapy (troglitazone and metformin)
      will lower both insulin and glucose levels as well as diminish dyslipidemia and
      hypertension. In contrast, sulfonylurea agents lower glucose by increasing
      insulin levels and may increase the risk of cardiovascular events. Therapy
      including aspirin, lipid agents (for example, statins), angiotensin-converting
      enzyme inhibitors, beta-adrenergic blockers, postmenopausal estrogen replacement,
      and vitamin E should be considered for patients with type 2 diabetes. In most
      patients with diabetes who have multivessel coronary artery disease, coronary
      artery bypass grafting is superior to coronary angioplasty for improving long
      term cardiovascular prognosis. This superiority is mediated in part by the use of
      a left internal mammary graft to the left anterior descending coronary artery.
      Urgent coronary angioplasty or thrombolytic therapy should be considered for all
      patients with diabetes who have acute myocardial infarction.

PMID- 10069358
TI  - 33-year-old man with chest pain and fever.

PMID- 10069359
TI  - The cephalosporins.
AB  - The cephalosporins are a large group of related beta-lactam antimicrobial agents.
      Favorable attributes of the cephalosporins include low rates of toxicity,
      relatively broad spectrum of activity, and ease of administration. Various
      cephalosporins are effective for treatment of many conditions, including
      pneumonia, skin and soft tissue infections, bacteremia, and meningitis.
      Differences among the numerous cephalosporin antimicrobial agents are sometimes
      subtle; however, an understanding of these differences is essential for optimal
      use of these agents. As a result of widespread use of cephalosporins, bacterial
      resistance to these drugs is increasingly common. New, fourth-generation agents
      (such as cefepime) offer an alternative for the treatment of infections caused by
      some drug-resistant microorganisms.

PMID- 10069360
TI  - The German Pflegeversicherung (long-term care insurance).
AB  - The German Pflegeversicherung, introduced in January 1995, has been very
      successful. It has been well accepted by persons in need and by their relatives
      and friends, providing benefits for both parties. The insurance is financially
      sound and has helped to create new workplaces.

PMID- 10069361
TI  - Gender diversity--struggle in the glass house.

PMID- 10069362
TI  - Cyclooxygenase-dependent signalling: molecular events and consequences.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) currently attract large interest.
      Next to pain relief, NSAIDs have important anti-thrombotic and anti-oncogenic
      effects. NSAIDs exert their action by inhibition of cyclooxygenase, the enzyme
      responsible for the production of prostanoids. Prostanoid signal transduction is
      still poorly understood, but it has become clear that these inflammatory lipids
      influence cellular physiology at three different levels: (1) activation of a 7 x
      transmembrane receptor coupled to heterotrimeric G proteins, (2) the inhibition
      of inflammation by activating corticosteroid-like receptors, (3) participation in
      receptor protein tyrosine kinase signal transduction. In this review prostanoid
      signalling at these three different levels will be reviewed and the relevance in
      (patho)physiological processes will be evaluated.

PMID- 10069363
TI  - Identification of a ribonuclease H gene in both Mycoplasma genitalium and
      Mycoplasma pneumoniae by a new method for exhaustive identification of ORFs in
      the complete genome sequences.
AB  - Exhaustive identification of open reading frames in complete genome sequences is
      a difficult task. It is possible that important genes are missed. In our efforts
      to reanalyze the intergenic regions of Mycoplasma genitalium and Mycoplasma
      pneumoniae, we have newly identified a number of new open reading frames (ORFs)
      in both M. genitalium and M. pneumoniae. The most significant identification was
      that of a ribonuclease H enzyme in both species which until now has not been
      identified or assumed absent and interpreted as such. In this paper we discuss
      the biological importance of RNase H and its evolutionary implication. We also
      stress the usefulness of our method for identifying new ORFs by reanalyzing
      intergenic regions of existing ORFs in complete genome sequences.

PMID- 10069364
TI  - Rhophilin, a small GTPase Rho-binding protein, is abundantly expressed in the
      mouse testis and localized in the principal piece of the sperm tail.
AB  - Tissue distribution and cellular localization of rhophilin, a 71 kDa Rho-binding
      protein, were examined in mice. Rhophilin mRNA was highly expressed in adult
      testis, but was absent in the testis of W/WV mice deficient in germ cells. An
      anti-rhophilin antibody detected a band of an expected size in sperm extracts,
      which was enriched in the tail fraction. Immunofluorescence analysis revealed two
      lines of striated staining running in parallel in the principal piece of the
      sperm tail. These results suggest that rhophilin is expressed in germ cells and
      localized in the fibrous sheath of the sperm tail.

PMID- 10069365
TI  - Distortion of the L-->M transition in the photocycle of the bacteriorhodopsin
      mutant D96N: a time-resolved step-scan FTIR investigation.
AB  - The D96N mutant of bacteriorhodopsin has often been taken as a model system to
      study the M intermediate of the wild type photocycle due to the long life time of
      the corresponding intermediate of the mutant. Using time-resolved step-scan FTIR
      spectroscopy in combination with a sample changing wheel we investigated the
      photocycle of the mutant with microsecond time resolution. Already after several
      microseconds an intermediate similar to the MN state is observed, which contrasts
      with the M state of the wild type protein. At reduced hydration M and N
      intermediates similar to those of wild type BR can be detected. These results
      have a bearing on the interpretation of the photocycle of this mutant. A
      mechanism is suggested for the fast rise of MN which provides some insight into
      the molecular events involved in triggering the opening of the cytosolic channel
      also of the wild type protein.

PMID- 10069366
TI  - Amino acid residues in the transmembrane domain of the type 1 sigma receptor
      critical for ligand binding.
AB  - The type 1 sigma receptor expressed in Xenopus oocytes showed binding abilities
      for the sigma-1 ligands, [3H](+)pentazocine and [3H]NE-100, with similar kinetic
      properties as observed in native tissue membranes. Amino acid substitutions
      (Ser99Ala, Tyr103Phe and di-Leu105,106di-Ala) in the transmembrane domain did not
      alter the expression levels of the type 1 sigma receptor as determined by
      immunoblot analysis using an anti-type 1 sigma receptor antiserum. By contrast,
      ligand binding was significantly suppressed by the substitutions. These findings
      provide evidence that the transmembrane domain of the type 1 sigma receptor plays
      a critical role in ligand binding of this receptor.

PMID- 10069367
TI  - Role of the third intracellular loop of the angiotensin II receptor subtype AT2
      in ligand-receptor interaction.
AB  - Angiotensin II (Ang II) receptor subtypes AT1 and AT2 share 34% overall homology,
      but the least homology is in their third intracellular loop (3rd ICL). In an
      attempt to elucidate the role of the 3rd ICL in determining the similarities and
      differences in the functions of the AT1 and the AT2 receptors, we generated a
      chimeric receptor in which the 3rd ICL of the AT2 receptor was replaced with that
      of the AT1 receptor. Ligand-binding properties and signaling properties of this
      receptor were assayed by expressing this receptor in Xenopus oocytes. Ligand
      binding studies using [125I-Sar1-Ile8] Ang II, a peptidic ligand that binds both
      the AT1 and the AT2 receptor subtypes, and 125I-CGP42112A, a peptidic ligand that
      is specific for the AT2 receptor, showed that the chimeric receptor has lost
      affinity to both ligands. However, IP3 levels of the oocytes expressing the
      chimeric receptor were comparable to the IP3 levels of the oocytes expressing the
      AT1 receptor, suggesting that the chimeric receptors could couple to
      phospholipase C pathway in response to Ang II. We have shown previously that the
      nature of the amino acid present in the position 215 located in the fifth
      transmembrane domain (TMD) of the AT2 receptor plays an important role in
      determining its affinity to different ligands. Our results from the ligand
      binding studies of the chimeric receptor further support the idea that the
      structural organization of the region spanning the 5th TMD and the 3rd ICL of the
      AT2 receptor has an important role in determining the ligand-binding properties
      of this receptor.

PMID- 10069368
TI  - The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY
      repressor.
AB  - Expression of the cop operon which effects copper homeostasis in Enterococcus
      hirae is controlled by the copper responsive repressor CopY. Purified Zn(II)CopY
      binds to a synthetic cop promoter fragment in vitro. Here we show that the 8 kDa
      protein CopZ acts as a copper chaperone by specifically delivering copper(I) to
      Zn(II)CopY and releasing CopY from the DNA. As shown by gel filtration and
      luminescence spectroscopy, two copper(I) are thereby quantitatively transferred
      from Cu(I)CopZ to Zn(II)CopY, with displacement of the zinc(II) and transfer of
      copper from a non-luminescent, exposed, binding site in CopZ to a luminescent,
      solvent shielded, binding site in CopY.

PMID- 10069369
TI  - Expression of plasminogen-related gene B varies among normal tissues and
      increases in cancer tissues.
AB  - We previously found that the promoter activity of plasminogen (PLG)-related gene
      B (PRGB) was 5-fold that of PLG. We have since examined the transcript levels of
      PRGB among various normal human tissues, and compared these findings with those
      of PLG. Reverse transcription-PCR analysis revealed that the PRGB expression
      varied widely among different tissues, while PLG was expressed only in the liver
      and kidney. RNA samples obtained from cultured cell lines also demonstrated
      differing PRGB expression. Furthermore, increased PRGB expression was observed in
      several fresh samples of cancer tissue obtained from cancer patients when
      compared with surrounding normal tissues.

PMID- 10069370
TI  - Evolution of visual pigments in geckos.
AB  - Most geckos are nocturnal forms and possess rod retinas, but some diurnal genera
      have pure-cone retinas. We isolated cDNAs encoding the diurnal gecko opsins, dg1
      and dg2, similar to nocturnal gecko P521 and P467, respectively. Despite the
      large morphological differences between the diurnal and nocturnal gecko
      photoreceptor types, they express phylogenetically closely related opsins. These
      results provide molecular evidence for the reverse transmutation, that is, rods
      of an ancestral nocturnal gecko have backed into cones of diurnal geckos. The
      amino acid substitution rates of dgl and dg2 are higher than those of P521 and
      P467, respectively. Changes of behavior regarding photic environment may have
      contributed to acceleration of amino acid substitutions in the diurnal gecko
      opsins.

PMID- 10069371
TI  - Submitochondrial and subcellular distributions of the carnitine-acylcarnitine
      carrier.
AB  - The submitochondrial and subcellular distributions of the carnitine-acylcarnitine
      translocase (CAC) have been studied. CAC is enriched to a much lesser extent than
      the carnitine palmitoyltransferases within the contact sites of mitochondria. A
      high-abundance protein of identical molecular size as the mitochondrial CAC that
      is immunoreactive with an anti-peptide antibody raised against a linear epitope
      of mitochondrial CAC is present in peroxisomes but not in microsomes. This
      suggests that CAC is targeted to at least two different locations within the
      liver cell and that acylcarnitine transport into peroxisomes is CAC mediated.

PMID- 10069372
TI  - Regulation of the human apolipoprotein AIV gene expression in transgenic mice.
AB  - The apolipoprotein (Apo) AI-CIII-AIV gene cluster has a complex pattern of gene
      expression that is modulated by both gene- and cluster-specific cis-acting
      elements. In particular the regulation of Apo AIV expression has been previously
      studied in vivo and in vitro including several transgenic mouse lines but a
      complete, consistent picture of the tissue-specific controls is still missing. We
      have analysed the role of the Apo AIV 3' flanking sequences in the regulation of
      gene expression using both in vitro and in vivo systems including three lines of
      transgenic mice. The transgene consisted of a human fragment containing 7 kb of
      the 5' flanking region, the Apo AIV gene itself and 6 kb of the 3' flanking
      region (-7+6 Apo AIV). Accurate analysis of the Apo AIV mRNA levels using
      quantitative PCR and Northern blots showed that the 7+6 kb Apo AIV fragment
      confers liver-specific regulation in that the human Apo AIV transgene is
      expressed at approximately the same level as the endogenous mouse Apo AIV gene.
      In contrast, the intestinal regulation of the transgene did not follow, the
      pattern observed with the endogenous gene although it produced a much higher
      intestinal expression following the accepted human pattern. Therefore, this
      animal model provides an excellent substrate to design therapeutic protocols for
      those metabolic derangements that may benefit from variations in Apo AIV levels
      and its anti-atherogenic effect.

PMID- 10069373
TI  - Intercellular traffic of human immunodeficiency virus type 1 transactivator
      protein defined by monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) directed against the amino-terminal region (N
      terminal sequence 2-19) of transactivator protein (tat) of HIV-1 have been shown
      to inhibit intercellular transactivation mediated by the extracellular tat
      protein. The intracellular transactivation was not significantly affected by anti
      tat mAbs. The specificity of anti-tat mAbs in abolishing the transactivating
      potential of extracellular tat is documented by studies with mAbs to HIV-1
      reverse transcriptase, or to a human mammary cancer protein. None of these
      antibodies showed any inhibitory effect on intercellular transactivation.
      Specific interaction of anti-tat IgG with tat protein expressed in Jurkat cells
      is further supported by experiments on immunoblotting. Extracellular tat is
      responsible for signals which induce a variety of biological responses in HIV
      infected cells, as well as in uninfected cells. The fact that anti-tat mAbs can
      abolish the intercellular traffic of tat protein offers a unique strategy in the
      development of vaccines against AIDS.

PMID- 10069374
TI  - Synthetic mammalian C-type natriuretic peptide forms large cation channels.
AB  - We report the first evidence that synthetic human C-type natriuretic peptide-22
      and the OaC-type natriuretic peptide-39(18-39), a 22 amino acid fragment of the
      OaC-type natriuretic peptide-39 from platypus venom, can function directly by
      forming a novel voltage-gated weakly cation-selective channel in negatively
      charged artificial lipid bilayer membranes. The channel activity is characterized
      by a tendency for inactivation at negative voltages, e.g. -60 and -70 mV, whereas
      at positive voltages the channel is fully open. The channel has a maximal cord
      conductance of 546+/-23 pS (n = 16) and shows weak outward rectification. The
      sequence and the permeability ratios were P(K)+: P(Cs)+: P(Na)+: P(choline)+
      1:0.88:0.76:0.13, respectively. The addition of 50 mM TEA+ cis (a blocker of
      outwardly rectifying K+ channels), 20 mM Cs+ cis (a blocker of inwardly
      rectifying K+ channels) or 0.5 mM glibenclamide cis (a blocker of ATP-sensitive
      K+ channels) to the cis chamber did not affect the conductance or the kinetics of
      the OaC-type natriuretic peptide-39(18-39)-formed channels (n = 2-5). It is
      concluded that the weak cation selectivity, large conductance and high open
      probability as well as their voltage dependency are consistent with the ability
      of these peptides to cause that loss of compartmentation of the membrane, which
      is a characteristic feature of adverse conditions that cause C-type natriuretic
      peptide-related pathologies.

PMID- 10069375
TI  - Functional dissection of the R domain of cystic fibrosis transmembrane
      conductance regulator.
AB  - Exogenously expressed unphosphorylated sub-domains of the R domain block CFTR Cl-
      channels in the planar lipid bilayer, though the block differs from block with
      full length R domain. Full length R domain peptide (aa 588-855) blocks CFTR Cl-
      channels quickly, completely and permanently. Two sub-domains, RD1RD2 (aa 588
      805) and RD2TM (aa 672-855), also inhibit CFTR Cl- channels, but the block takes
      longer to effect and is not complete. Shorter sequences, RD1 (aa 588-746) and RD2
      (aa 672-805), fail to effect any block. These data suggest that either the amino
      terminal or carboxy-terminal portions of the R domain protein or its stabilized
      secondary structure are critical to functional regulation.

PMID- 10069376
TI  - Rho-kinase in human neutrophils: a role in signalling for myosin light chain
      phosphorylation and cell migration.
AB  - The role of a Rho-associated coiled-coil forming kinase in migration of
      neutrophils has been investigated. Rho-associated coiled-coil forming kinase I
      was expressed in human neutrophils. Chemotactic peptide led to a Rho-associated
      coiled-coil forming kinase-dependent increase in phosphorylation of myosin light
      chain. This was determined with the help of an antibody directed against serine
      19-phosphorylated myosin light chain and an inhibitor of Rho-associated coiled
      coil forming kinase (Y-27632). Y-27632 suppressed myosin light chain
      phosphorylation and chemotactic peptide-induced development of cell polarity and
      locomotion with similar potency (ED50 0.5-1.1 microM). The data strongly suggest
      that a Rho-associated coiled-coil forming kinase isoform, activated in human
      neutrophils exposed to chemotactic peptide, is important for motile functions of
      these cells.

PMID- 10069377
TI  - Arginine-aminoglycoside conjugates that bind to HIV transactivation responsive
      element RNA in vitro.
AB  - HIV gene expression is crucially dependent on binding of the viral Tat protein to
      the transactivation RNA response element. A number of synthetic Tat
      transactivation responsive element interaction inhibitors of peptide/peptoid
      nature were described as potential antiviral drug prototypes. We present a new
      class of peptidomimetic inhibitors, conjugates of L-arginine with
      aminoglycosides. Using a gel-shift assay and affinity chromatography on an L
      arginine column we found that these compounds bind specifically to the
      transactivation responsive element RNA in vitro with Kd values in the range of 20
      400 nM, which is comparable to the Kd of native Tat bound to the transactivation
      responsive element (10-12 nM). Confocal microscopy studies demonstrated that
      fluorescein-labelled conjugate penetrates into live cells. High affinity to the
      transactivation responsive element, low toxicity, and relative simplicity of
      synthesis make these compounds attractive candidates for antiviral drug design.

PMID- 10069378
TI  - Purification and characterization of rat hippocampal CA3-dendritic spines
      associated with mossy fiber terminals.
AB  - We report a revised and improved isolation procedure for CA3-dendritic spines,
      most of them still in association with mossy fiber terminals resulting in a 7.5
      fold enrichment over nuclei and a 29-fold enrichment over myelin. Additionally,
      red blood cells, medullated fibers, mitochondria and small synaptosomes were
      significantly depleted. We show by high resolution electron microscopy that this
      subcellular fraction contains numerous dendritic spines with a rich
      ultrastructure, e.g. an intact spine apparatus, membranous organelles, free and
      membrane-bound polyribosomes, endocytic structures and mitochondria. This
      improved experimental system will allow us to study aspects of post-synaptic
      functions at the biochemical and molecular level.

PMID- 10069379
TI  - Tyrosine kinase-dependent modulation by interferon-alpha of the ATP-sensitive K+
      current in rabbit ventricular myocytes.
AB  - We examined the effects of interferon-alpha on the ATP-sensitive K+ current
      (IK,ATP) in rabbit ventricular cells using the patch-clamp technique. IK,ATP was
      induced by NaCN. Whole-cell experiments indicated that interferon-alpha (5 x
      10(2) - 2.4 x 10(4) U/ml) inhibited IK,ATP in a concentration-dependent manner
      (60.7+/-7.5% with 2.4 x 10(4) U/ml). In cell-attached configuration, interferon
      alpha (2.4 x 10(4) U/ml) applied to the external solution also inhibited the
      activity of the single ATP-sensitive K+ (KATP) channel by 56.0+/-5.8% without
      affecting the single channel conductance. The inhibitory effect of IK,ATP by
      interferon-alpha was blocked by genistein and herbimycin A, tyrosine kinase
      inhibitors, but was not affected by N-(2-metylpiperazyl)-5-isoquinolinesulfoamide
      (H-7), an inhibitor of protein kinase C and cAMP-dependent protein kinase. These
      findings suggest that interferon-alpha inhibits the cardiac KATP channel through
      the activation of tyrosine kinase. The tyrosine kinase-mediated inhibition of
      IK,ATP by cytokines may aggravate cell damage during myocardial ischemia.

PMID- 10069380
TI  - Impact of 9-(2-phosphonylmethoxyethyl)adenine on (deoxy)ribonucleotide metabolism
      and nucleic acid synthesis in tumor cells.
AB  - Following exposure to 9-(2-phosphonylmethoxyethyl)adenine (an inhibitor of the
      cellular DNA polymerases alpha, delta and epsilon), human erythroleukemia K562,
      human T-lymphoid CEM and murine leukemia L1210 cells markedly accumulated in the
      S phase of the cell cycle. In contrast to DNA replication, RNA synthesis
      (transcription) and protein synthesis (mRNA translation) were not affected by 9
      (2-phosphonylmethoxyethyl)-adenine. The ribonucleoside triphosphate pools were
      slightly elevated, while the intracellular levels of all four deoxyribonucleoside
      triphosphates were 1.5-4-fold increased in 9-(2-phosphonylmethoxyethyl)adenine
      treated K562, CEM and L1210 cells. The effect of 9-(2
      phosphonylmethoxyethyl)adenine on de novo (thymidylate synthase-mediated) and
      salvage (thymidine kinase-mediated) dTTP synthesis was investigated using radio
      labelled nucleoside precursors. The amount of thymidylate synthase-derived dTTP
      in the acid soluble pool was 2-4-fold higher in PMEA-treated than in untreated
      K562 cells, which is in accord with the 3-4-fold expansion of the global dTTP
      level in the presence of 9-(2-phosphonylmethoxyethyl)adenine. Strikingly, 2
      derived dTTP accumulated to a much higher extent (i.e. 16-40-fold) in the soluble
      dTTP pool upon 9-(2-phosphonylmethoxyethyl)adenine treatment. In keeping with
      this finding, a markedly increased thymidine kinase activity could be
      demonstrated in extracts of 9-(2-phosphonylmethoxyethyl)adenine-treated K562 cell
      cultures. Also, in the presence of 200 microM 9-(2
      phosphonylmethoxyethyl)adenine, 14-fold less thymidylate synthase-derived but
      only 3-fold less thymidine kinase-derived dTTP was incorporated into the DNA of
      the K562 cells. These data show that thymidine incorporation may be inappropriate
      as a cell proliferation marker in the presence of DNA synthesis inhibitors such
      as 9-(2-phosphonylmethoxyethyl)adenine. Our findings indicate that 9-(2
      phosphonylmethoxyethyl)adenine causes a peculiar pattern of (deoxy)ribonucleotide
      metabolism deregulation in drug-treated tumor cells, as a result of the metabolic
      block imposed by the drug on the S phase of the cell cycle.

PMID- 10069381
TI  - Antioxidant-mediated inhibition of the heat shock response leads to apoptosis.
AB  - We examined the hypothesis that reactive oxygen species (ROS) contribute to the
      induction of heat shock proteins (hsps) during stress response. Exposure of HL-60
      human myelocytic cells to 42 degrees C induced both hsp72 and hsp27. In the
      presence of the antioxidant molecules pyrrolidine dithiocarbamate or 1,10
      phenanthroline induction of hsp72 and 27 was significantly decreased, while N
      acetyl-L-cysteine caused a slight reduction. Prevention of hsp induction was
      associated with heat sensitization and increased caspase activity, indicating
      that the cells were undergoing apoptosis. These data suggest that ROS contribute
      to the induction of hsps and furthermore, that hsp induction and apoptosis are
      mutually exclusive events within the same cell.

PMID- 10069382
TI  - Substrate specificity of catechol oxidase from Lycopus europaeus and
      characterization of the bioproducts of enzymic caffeic acid oxidation.
AB  - The substrate specificity of catechol oxidase from Lycopus europaeus towards
      phenols is examined. The enzyme catalyzes the oxidation of o-diphenols to o
      quinones without hydroxylating monophenols, the additional activity of
      tyrosinase. Substrates containing a -COOH group are inhibitors for catechol
      oxidase. The products of enzymic oxidation of caffeic acid were analyzed and
      isolated by HPLC with diode array detection. The neolignans of the 2,3-dihydro
      1,4-benzodioxin type (3, 6-8), 6,7-dihydroxy-1-(3,4-dihydroxyphenyl)-2,3
      dicarboxy-1,2-dihydro naphthaline (1) 6,7-dihydroxy-1-(3,4-dihydroxyphenyl)-3
      carboxynaphthaline (5) and 2,6-bis-(3',4'-dihydroxyphenyl)-1-carboxy-3-oxacyclo
      (3,0)-pent an-2-on-1-ene (4) were formed. A reaction mechanism for the formation
      of (1, 4 and 5) is discussed.

PMID- 10069383
TI  - A unique DNase activity shares the active site with ATPase activity of the
      RecA/Rad51 homologue (Pk-REC) from a hyperthermophilic archaeon.
AB  - A RecA/Rad51 homologue from Pyrococcus kodakaraensis KOD1 (Pk-REC) is the
      smallest protein among various RecA/Rad51 homologues. Nevertheless, Pk-Rec is a
      super multifunctional protein and shows a deoxyribonuclease activity. This
      deoxyribonuclease activity was inhibited by 3 mM or more ATP, suggesting that the
      catalytic centers of the ATPase and deoxyribonuclease activities are overlapped.
      To examine whether these two enzymatic activities share the same active site, a
      number of site-directed mutations were introduced into Pk-REC and the ATPase and
      deoxyribonuclease activities of the mutant proteins were determined. The mutant
      enzyme in which double mutations Lys-33 to Ala and Thr-34 to Ala were introduced,
      fully lost both of these activities, indicating that Lys-33 and/or Thr-34 are
      important for both ATPase and deoxyribonuclease activities. The mutation of Asp
      112 to Ala slightly and almost equally reduced both ATPase and deoxyribonuclease
      activities. In addition, the mutation of Glu-54 to Gln did not seriously affect
      the ATPase, deoxyribonuclease, and UV tolerant activities. These results strongly
      suggest that the active sites of the ATPase and deoxyribonuclease activities of
      Pk-REC are common. It is noted that unlike Glu-96 in Escherichia coli RecA, which
      has been proposed to be a catalytic residue for the ATPase activity, the
      corresponding residual Glu-54 in Pk-REC is not involved in the catalytic function
      of the protein.

PMID- 10069384
TI  - Caspase-1 is not involved in experimental hepatitis in mouse.
AB  - Experimental hepatitis induced by tumor necrosis factor in D-(+)-galactosamine
      sensitized mice or by an agonistic anti-Fas antibody in normal mice is
      accompanied by dramatic apoptosis of hepatocytes. Apoptosis is the final result
      of activation of a cascade of caspases. We used caspase-1-/- mice, generated by
      gene targeting, to study the role of this protease in TNF- and anti-Fas-induced
      lethal hepatitis. We found that mutant mice exhibited the typical caspase-1-/-
      phenotype, since they resisted to a lethal injection of LPS and released no
      interleukin-1beta in the circulation, in contrast to wild-type littermates. When
      caspase-1-/- mice were challenged with different doses of tumor necrosis factor/D
      (+)-galactosamine or with anti-Fas, no increased survival was observed compared
      with control mice. Furthermore, apoptosis in the livers of these mice and serum
      levels of alanine aminotransferase were not reduced. These data indicate that
      caspase-1 deficiency does not lead to reduced apoptosis in these models, either
      because caspase-1 is irrelevant in this model or because of functional
      redundancy.

PMID- 10069385
TI  - Interactions of heterologous DNA with polyomavirus major structural protein, VP1.
AB  - 'Empty' polyomavirus pseudocapsids, self-assembled from the major structural
      protein VP1, bind DNA non-specifically and can deliver it into the nuclei of
      mammalian cells for expression [Forstova et al. (1995) Hum. Gene Ther. 6, 297
      3061. Formation of suitable VP1-DNA complexes appears to be the limiting step in
      this route of gene delivery. Here, the character of VP1-DNA interactions has been
      studied in detail. Electron microscopy revealed that VP1 pseudocapsids can create
      in vitro at least two types of interactions with double-stranded DNA: (i) highly
      stable complexes, requiring free DNA ends, where the DNA is partially
      encapsidated; and, (ii) weaker interactions of pseudocapsids with internal parts
      of the DNA chain.

PMID- 10069386
TI  - Domain organization of flagellar hook protein from Salmonella typhimurium.
AB  - Hook forms a universal joint, which mediates the torque of the flagellar motor to
      the outer helical filaments. Domain organization of hook protein from Salmonella
      typhimurium was investigated by exploring thermal denaturation properties of its
      proteolytic fragments. The most stable part of hook protein involves residues 148
      to 355 and consists of two domains, as revealed by deconvolution analysis of the
      calorimetric melting profiles. Residues 72-147 and 356-370 form another domain,
      while the terminal regions of the molecule, residues 1-71 and 371-403, avoid a
      compact tertiary structure in the monomeric state. These folding domains were
      assigned to the morphological domains of hook subunits known from EM image
      reconstructions, revealing the overall folding of hook protein in its filamentous
      state.

PMID- 10069387
TI  - Sulfonylurea receptors set the maximal open probability, ATP sensitivity and
      plasma membrane density of KATP channels.
AB  - KATP channels are heteromultimers of SUR and KIR6.2. C-terminal truncation of
      KIR6.2 allows surface expression of the pore. KIR6.2deltaC35 channels display
      approximately 7-fold lower maximal open probability, approximately 35-fold
      reduced ATP sensitivity, reduced mean open time, a markedly increased transition
      rate from a burst into a long-lived closed state, and have no counterpart in
      vivo. SUR1 and SUR2A restore wild-type bursting, ATP sensitivity and increase
      channel density in the plasma membrane. The high IC50(ATP) of approximately 4 mM
      for KIR6.2deltaCK185Q channels results from the additive effects of SUR removal
      and KIR6.2 modification. The results demonstrate allosteric interaction(s) are
      essential for normal intrinsic activity, ATP inhibition, and trafficking of KATP
      channels.

PMID- 10069388
TI  - On the binding of ATP to the autophosphorylating protein, Ptk, of the bacterium
      Acinetobacter johnsonii.
AB  - The autophosphorylating protein, Ptk, of the bacterium Acinetobacter johnsonii
      was overproduced, purified to homogeneity and assayed for ATP binding by using
      the nucleotide analog 5'-p-fluorosulfonylbenzoyl adenosine. The ATP binding site
      of this bacterial autophosphorylating protein was found to be different from that
      generally used by eukaryotic protein kinases. It consists of two amino acid
      sequences that closely resemble the Walker motifs A and B. This observation was
      confirmed by site-directed mutagenesis experiments which showed, in addition,
      that the ATP molecule bound to these motifs is effectively employed by the
      bacterial protein to autophosphorylate on tyrosine. It is concluded that even
      though the overall autophosphorylation reaction is similar in eukaryotic and
      prokaryotic proteins, the mechanism involved is likely different.

PMID- 10069389
TI  - Application of metabolic control analysis to the study of toxic effects of copper
      in muscle glycolysis.
AB  - Experimental and model studies have been performed to characterise the effects of
      Cu2+ on the activities of individual glycolytic enzymes and on the flux and
      internal metabolite concentrations of the upper part of glycolysis in mouse
      muscle extracts. Cu2+ significantly inhibited the triosephosphate production from
      glucose with an IC50 of about 6.0 microM. At a similar extension Cu2+ inhibited
      hexokinase and phosphofructokinase, with an IC50 of 6.2 microM and 6.4 microM
      respectively, whereas the effects on the activities of aldolase, phosphoglucose
      isomerase and the internal metabolite levels were not significant. Flux control
      coefficients and flux response coefficients were determined in the presence of
      copper concentrations between 0 and 10 microM. The same values of flux control
      coefficients for hexokinase and for phosphofructokinase (0.8 and 0.2
      respectively) were found in absence and in presence of copper. At Cu2+ equal to
      the flux IC50, the response coefficient was -1. The elasticity coefficients for
      hexokinase and phosphofructokinase at Cu2+ equal to the IC50 were also -1. A
      mathematical model was used to analyze the effect of copper on glycolysis under
      different conditions using experimental kinetic parameters and rate equations for
      enzymatic reactions of the upper part of glycolysis.

PMID- 10069390
TI  - Identification of caspases that cleave presenilin-1 and presenilin-2. Five
      presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases.
AB  - Mutations in the presenilin (PS) genes PSI and PS2 are involved in Alzheimer's
      disease (AD). Recently, apoptosis-associated cleavage of PS proteins was
      identified. Here we demonstrate that PS1 as well as PS2 are substrates for
      different members of the caspase protein family. Remarkably, the caspases acting
      on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and
      -11, cleaved PSI after residues ENDD329 and to a lesser extent after residues
      AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on
      AQRD341. Importantly, these two cleavage sites were also recognized by caspases
      in the C-terminal PS1 fragment produced by constitutive proteolysis. In
      decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the
      recognition site D326SYD329. Caspase-8 and -3 exhibited the highest proteolytic
      activity on both PS1 and PS2. PS1 and PS2 were not hydrolyzed by caspase-2 and
      PS2 also not by caspase-11. None of five missense mutations affected the
      sensitivity of PSI to caspase-mediated cleavage. This suggests that AD
      pathogenesis associated with PS1 missense mutations cannot be explained by a
      change in caspase-dependent processing.

PMID- 10069391
TI  - Overexpression of nucleoside diphosphate kinases induces neurite outgrowth and
      their substitution to inactive forms leads to suppression of nerve growth factor-
      and dibutyryl cyclic AMP-induced effects in PC12D cells.
AB  - Whether nucleoside diphosphate kinase (NDPK) is involved in neuronal
      differentiation was investigated with special reference to its enzyme activity.
      Neurite outgrowth of PC12D cells induced by nerve growth factor or a cyclic AMP
      analog was suppressed to some extent when inactive NDPKs (the active site
      histidine 118 was replaced with alanine), not active forms, were transiently
      overexpressed. This suppression was more definite in their stably expressed
      clones. NDPKbeta-transfected clones and, to a lesser extent, NDPKalpha
      transfected clones, but not inactive NDPK-transfected clones, extended neurites
      without differentiation inducers. These results imply that NDPKs may play a role
      by exerting their enzyme activity during differentiation of PC12 cells.

PMID- 10069392
TI  - Binding properties of the human homeodomain protein OTX2 to a DNA target
      sequence.
AB  - OTX2, a homeodomain protein essential in mouse for the development of structures
      anterior to rhombomere 3, binds with high affinity to a DNA element (called OTS)
      present in the human tenascin-C promoter. Here we investigate the binding
      properties of the full length recombinant human OTX2 and of several deletion
      mutants to the OTS element. We demonstrate that, upon binding of the protein to
      its DNA target site, a second molecule of OTX2 is recruited to the complex and
      that a nearby second binding site is not necessary for this interaction. OTX2
      sequences located within a region carboxyl-terminal to the homeodomain are
      necessary in addition to the homeodomain for binding to DNA. Furthermore, OTX2
      dimerization requires the same protein domains necessary for DNA binding.

PMID- 10069393
TI  - Antitumor activity of curcumin is mediated through the induction of apoptosis in
      AK-5 tumor cells.
AB  - Curcumin, the yellow pigment of turmeric (Curcuma longa), used commonly as a
      spice, has been shown to possess anticarcinogenic activity. Curcumin inhibited AK
      5 tumor growth and induced apoptosis in AK-5 cells. Curcumin induced apoptosis is
      mediated through the activation of caspase-3, which is specifically inhibited by
      the tetrapeptide Ac-DEVD-CHO. In addition, curcumin induced tumor cell death is
      caused through the generation of reactive oxygen intermediates which is inhibited
      by N-acetyl-L-cysteine. Our studies suggest that the apoptotic process induced by
      curcumin is the mechanism mediating AK-5 tumor cell death.

PMID- 10069394
TI  - The chloroplast infA gene with a functional UUG initiation codon.
AB  - All chloroplast genes reported so far possess ATG start codons and sometimes GTGs
      as an exception. Sequence alignments suggested that the chloroplast infA gene
      encoding initiation factor 1 in the green alga Chlorella vulgaris has TTG as a
      putative initiation codon. This gene was shown to be transcribed by RT-PCR
      analysis. The infA mRNA was translated accurately from the UUG codon in a tobacco
      chloroplast in vitro translation system. Mutation of the UUG codon to AUG
      increased translation efficiency approximately 300-fold. These results indicate
      that the UUG is functional for accurate translation initiation of Chlorella infA
      mRNA but it is an inefficient initiation codon.

PMID- 10069395
TI  - A tentative mechanism of the ternary complex formation between phosphorylase
      kinase, glycogen phosphorylase b and glycogen.
AB  - The kinetics of rabbit skeletal muscle phosphorylase kinase interaction with
      glycogen has been studied. At pH 6.8 the binding of phosphorylase kinase to
      glycogen proceeds only in the presence of Mg2+, whereas at pH 8.2 formation of
      the complex occurs even in the absence of Mg2+. On the other hand, the
      interaction of phosphorylase kinase with glycogen requires Ca2+ at both pH
      values. The initial rate of the complex formation is proportional to the enzyme
      and glycogen concentrations, suggesting the formation of the complex with
      stoichiometry 1:1 at the initial step of phosphorylase kinase binding by
      glycogen. According to the kinetic and sedimentation data, the substrate of the
      phosphorylase kinase reaction, glycogen phosphorylase b, favors the binding of
      phosphorylase kinase with glycogen. We suggest a model for the ordered binding of
      phosphorylase b and phosphorylase kinase to the glycogen particle that explains
      the increase in the tightness of phosphorylase kinase binding with glycogen in
      the presence of phosphorylase b.

PMID- 10069396
TI  - Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth
      factor.
AB  - Mammalian sensory neurons express a voltage-gated sodium channel named SNS. Here
      we report the identification of an SNS transcript (SNS-A) that contains an exact
      repeat of exons 12, 13 and 14 encoding a partial repeat of domain II. Because the
      exons 12-14 are present in single copies in genomic DNA, the SNS-A transcript
      must arise by trans-splicing. Nerve growth factor, which regulates pain
      thresholds, and the functional expression of voltage-gated sodium channels
      increases the levels of the SNS-A transcript several-fold both in vivo and in
      vitro as measured by RNase protection methods, as well as RT-PCR. These data
      demonstrate a novel regulatory role for the nerve growth factor and are the first
      example of trans-splicing in the vertebrate nervous system.

PMID- 10069397
TI  - Bacterial formate dehydrogenase. Increasing the enzyme thermal stability by
      hydrophobization of alpha-helices.
AB  - NAD+-dependent formate dehydrogenase (EC 1.2.1.2, FDH) from methylotrophic
      bacterium Pseudomonas sp.101 exhibits the highest stability among the similar
      type enzymes studied. To obtain further increase in the thermal stability of FDH
      we used one of general approaches based on hydrophobization of protein alpha
      helices. Five serine residues in positions 131, 160, 168, 184 and 228 were
      selected for mutagenesis on the basis of (i) comparative studies of nine FDH
      amino acid sequences from different sources and (ii) with the analysis of the
      ternary structure of the enzyme from Pseudomonas sp.101. Residues Ser-131 and Ser
      160 were replaced by Ala, Val and Leu. Residues Ser-168, Ser-184 and Ser-228 were
      changed into Ala. Only Ser/Ala mutations in positions 131, 160, 184 and 228
      resulted in an increase of the FDH stability. Mutant S168A was 1.7 times less
      stable than the wild-type FDH. Double mutants S(131,160)A and S(184,228)A and the
      four-point mutant S(131,160,184,228)A were also prepared and studied. All FDH
      mutants with a positive stabilization effect had the same kinetic parameters as
      wild-type enzyme. Depending on the position of the replaced residue, the single
      point mutation Ser/Ala increased the FDH stability by 5-24%. Combination of
      mutations shows near additive effect of each mutation to the total FDH
      stabilization. Four-point mutant S(131,160,184,228)A FDH had 1.5 times higher
      thermal stability compared to the wild-type enzyme.

PMID- 10069398
TI  - Carboxyatractyloside increases the effect of oleate on mitochondrial permeability
      transition.
AB  - Addition of a low concentration of carboxyatractyloside (0.075 microM) renders
      mitochondria susceptible to the opening of the non-specific pore by 5 microM
      oleate, in a cyclosporin A-sensitive fashion. Matrix Ca2+ efflux as well as
      collapse of the transmembrane potential reveal permeability transition. The
      effect of oleate is reached after the titration, by carboxyatractyloside, of 38
      pmol of adenine nucleotide translocase per mg mitochondrial protein. We propose
      that permeability transition may result from an additive action of
      carboxyatractyloside plus oleate on the ADP/ATP carrier.

PMID- 10069399
TI  - Single channel analysis of recombinant major outer membrane protein porins from
      Chlamydia psittaci and Chlamydia pneumoniae.
AB  - We recently demonstrated that the major outer membrane protein of Chlamydia
      psittaci, the primary vaccine candidate for combating chlamydial infections,
      functions as a porin-like ion channel. In this study, we have cloned, expressed
      and functionally reconstituted recombinant major outer membrane proteins from C.
      psittaci and Chlamydia pneumoniae and analysed them at the single channel level.
      Both form porin-like ion channels that are functionally similar to those formed
      by native C. psittaci major outer membrane protein. Also, like the native
      channels, recombinant C. psittaci channels are modified by a native major outer
      membrane protein-specific monoclonal antibody. This is the first time that native
      function has been demonstrated for recombinant chlamydial major outer membrane
      proteins. Future bilayer reconstitution will provide a strategy for detailed
      structure/function studies of this new subclass of bacterial porins and the work
      also has important implications for successful protein refolding and the
      development of improved subunit vaccines.

PMID- 10069400
TI  - Mitochondrial DNA sequence diversity in Russians.
AB  - The article presents the results of the first regular study of Russian
      populations by sequencing the control region of mitochondrial DNA (mtDNA). The
      sequenced region is the most variable on mtDNA molecule and is commonly used for
      population and evolutionary studies. Russians form one of the largest ethnic
      groups (more than 129 million). However, their genetic diversity had only been
      characterized with RFLP and biochemical markers, although there are already
      established mtDNA sequence databases for many ethnic groups of the world. We have
      obtained sequence data from 103 individuals living in three Russian regions:
      Kostroma, Kursk, and Rjazan. The sequenced fragment analyzed is 360 bp in length
      (positions from 16024 to 16383). Fifty nine nucleotide positions have been found
      polymorphic in Russians, among those were 57 transitions and two transversions.
      One individual is found having two insertions of two cytosines between positions
      16184 and 16193. Among 64 different mitotypes identified in the study 52 were
      unique in these samples. The index of genetic diversity (Nei, 1987) for Russians
      is 0.96. This value is within the established range for European populations
      (0.93 to 0.98). Genetic distances calculated from our data show that Russians
      form a cluster with Germans, Bulgarians, Swedes, Estonians, and Volgo-Finns are
      more distant from Karelians and Finns, and much more differ from Turks and
      especially Mongolians.

PMID- 10069401
TI  - 2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide (OPB-9195) treatment
      inhibits the development of intimal thickening after balloon injury of rat
      carotid artery: role of glycoxidation and lipoxidation reactions in vascular
      tissue damage.
AB  - We have pursued the hypothesis that the carbonyl modification of proteins by
      glycoxidation and lipoxidation reactions plays a role in atherogenesis. Human
      atherosclerotic tissues with fatty streaks and uremic arteriosclerotic tissues
      were examined, with specific antibodies, to detect protein adducts formed with
      carbonyl compounds by glycoxidation or lipoxidation reactions, i.e. advanced
      glycation end products (AGEs) or glycoxidation products, such as
      carboxymethyllysine (CML) and pentosidine, and lipoxidation products, such as
      malondialdehyde (MDA)-lysine and 4-hydroxy-nonenal (HNE)-protein adduct. All the
      four adducts were identified in the proliferative intima and in macrophage-rich
      fatty streaks. If the carbonyl modification is not a mere result but is a
      contributor to atherogenesis, inhibition of glycoxidation and lipoxidation
      reactions might prevent vascular tissue damage. We tested this hypothesis in rats
      following balloon injury of their carotid arteries, a model exhibiting a
      remarkable intimal thickening, which are stained positive for all the four
      adducts. Oral administration of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5
      ylacetanili de (OPB-9195), an inhibitor of both glycoxidation and lipoxidation
      reactions, in rats following balloon injury effectively prevented the intimal
      thickening. These data suggest a role for the carbonyl modification of proteins
      by glycoxidation and lipoxidation reactions in most, if not all, types of
      vascular tissue damage ('carbonyl stress'), and the usefulness of inhibitors of
      carbonyl reactions for the treatment of vascular tissue damage.

PMID- 10069402
TI  - Cellular localization and evolution of prolactin receptor mRNA in ovine
      endometrium during pregnancy.
AB  - In this study, we have investigated the expression of the prolactin receptor gene
      in ovine endometrium during oestrus cycle and pregnancy. Using reverse
      transcription-PCR analysis, we provided evidence that the prolactin receptor gene
      is specifically transcribed in this tissue. As shown by Northern blot analysis,
      the level of the prolactin receptor transcripts increased dramatically during
      late pregnancy. In situ hybridization experiments revealed that prolactin
      receptor mRNA was specifically expressed in the glandular compartment and
      confirmed the dramatic increase of its expression that occurs at the end of
      pregnancy. Taken together, these findings are consistent with a putative role of
      prolactin and/or related molecules in the regulation of the proliferation of the
      glandular compartment and/or in the control of the secretory activity of the
      endometrium.

PMID- 10069403
TI  - Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals.
AB  - Simultaneously produced superoxide/nitric oxide radicals (O2*-/NO*) could form
      peroxynitrite (OONO-) which has been found to cause atherogenic, i.e. oxidative
      modification of LDL. Aromatic hydroxylation and nitration of the aspirin
      metabolite salicylate by OONO- has been reported. Therefore we tested if
      salicylate may be able to protect LDL from oxidation by O2*-/NO* by scavenging
      the OONO reactive decomposition products. When LDL was exposed to simultaneously
      produced O2*-/NO* using the sydnonimine SIN-1, salicylate exerted an inhibitory
      effect on LDL oxidation as measured by TBARS and lipid hydroperoxide formation
      and alteration in electrophoretic mobility of LDL. The cytotoxic effect of SIN-1
      pre-oxidised LDL to endothelial cells was also diminished when salicylate was
      present during SIN-1 treatment of LDL. Spectrophotometric analysis revealed that
      salicylate was converted to dihydroxybenzoic acid (DHBA) derivatives in the
      presence of SIN-1. 2,3- and 2,5-DHBA were even more effective to protect LDL from
      oxidation by O2*-/NO*. Because O2*-/NO* can occur in vivo, the results may
      indicate that salicylate could act as an efficacious inhibitor of O2*-/NO*
      initiated atherogenic LDL modification, thus further supporting the rationale of
      aspirin medication regarding cardiovascular diseases.

PMID- 10069404
TI  - Immunohistochemical localization of 5-oxo-L-prolinase, an enzyme of the gamma
      glutamyl cycle, in porcine brain microvessels.
AB  - The immunohistochemical analysis of the distribution of 5-oxo-L-prolinase in
      porcine brain at the light microscopic level was performed with an antibody
      raised against the enzyme purified from pig kidney. The present study reveals the
      specific expression of 5-oxo-L-prolinase in brain capillaries with an average
      diameter of 4.1+/-0.9 microm, while larger blood vessels remain unstained.
      Porcine kidney and skeletal muscle show no endothelial-specific staining with the
      antibody. In some cases, the asymmetrical staining pattern in cross and
      longitudinal sections of brain microvessels indicate endothelial- but also
      pericyte-specific expression.

PMID- 10069405
TI  - Improving outcomes in elderly patients with asthma.
AB  - Although often regarded as a disease of childhood, asthma is common in elderly
      people. Although recent figures show a decline over the past few years in the
      number of asthma deaths in children and younger adults, the same is not true of
      older adults, in whom most asthma deaths occur. Differences between asthma in
      young and old patients are seen not only in response to treatment. The
      nonspecific presentation of asthma in elderly adults means that the diagnosis of
      asthma is difficult to make. In addition, research suggests that physicians are
      reluctant to use spirometry and measurement of reversibility when investigating
      respiratory symptoms in old people. This leads to a tendency to label breathless
      or wheezy elderly patients as having chronic obstructive pulmonary disease (COPD)
      rather than asthma. In turn, patients with a diagnosis of COPD are less likely to
      be treated with bronchodilators and corticosteroids. Treatment guidelines for the
      management of asthma in children and younger adults may need to be adapted when
      applied to older patients. Reduced perception of bronchoconstriction may lead to
      underuse of bronchodilators prescribed 'as required'. The bronchodilator response
      to beta2-agonists is attenuated as part of the normal aging process, and other
      groups of bronchodilator medications should be considered. Inhaler technique can
      be a particular problem in elderly patients with asthma, requiring careful choice
      of inhaler device. However, the frequent presence of multiple pathology and
      multiple medication in this age group enhances the risk of adverse effects from
      oral preparations, and so the inhaled route should be preferred wherever
      possible. Underestimation of the severity of an acute exacerbation of asthma by
      both patient and doctor has been suggested as a contributory factor to poor
      outcome in older people. Since the cardiovascular responses to hypoxia and
      bronchoconstriction tend to diminish with increasing age, objective measures of
      asthma severity (peak flow monitoring and blood gas estimation) are essential in
      this age group.

PMID- 10069408
TI  - Assessment of the risk for venous thromboembolism among users of hormone
      replacement therapy.
AB  - Although hormone replacement therapy (HRT) provides health benefits, concerns
      about harmful effects have been raised, including an increased risk of venous
      thromboembolism. The purpose of this review is to assess the risk for venous
      thromboembolism associated with HRT. Data searches involved the MEDLINE database
      from January 1982 to December 1997, and bibliographies of retrieved articles.
      Seven case-control studies and 1 prospective cohort study considering venous
      thromboembolism as the outcome of interest were selected and rated according to
      methodological criteria. Results of case-controls studies were pooled to
      determine an overall estimate. The pooled risk ratio (95% confidence interval)
      for venous thromboembolism among current users of HRT compared with non-users
      (never-users and past-users combined) was 2.1 (1.4 to 3.0) in the case-control
      studies (n = 7). Based on one prospective cohort study, the risk of primary
      pulmonary embolism associated with HRT was 2.1 (1.2 to 3.8). No association was
      found with past use of HRT. The risk of venous thromboembolism was higher within
      the first year of treatment. There was no strong evidence for a dose-response
      relationship with estrogen. No striking difference in risk of venous
      thromboembolism was observed between unopposed and opposed regimens. The small
      number of women using transdermal estrogen therapy precluded any firm conclusions
      about the impact of the route of estrogen administration. Current use of oral
      estrogen as HRT is associated with a 2- to 3-fold increased risk of venous
      thromboembolism. However, the absolute risk remains low, and these findings need
      to be weighed against the potential benefits of treatment. Whether transdermal
      estrogen therapy is safe with respect to venous thromboembolism has yet to be
      adequately investigated.

PMID- 10069409
TI  - Cilostazol.
AB  - Cilostazol is an antiplatelet agent with vasodilating properties that has been
      used in the treatment of patients with peripheral ischaemia such as intermittent
      claudication. The drug inhibits platelet aggregation induced by ADP, collagen and
      arachidonic acid. Unlike aspirin (acetylsalicylic acid), cilostazol inhibits both
      primary and secondary aggregation. It also acts as a vascular vasodilator by
      inhibiting calcium-induced contractions while having no direct effect on
      contractile proteins. In double-blind randomised trials, patients with
      intermittent claudication receiving cilostazol showed significant improvements
      versus placebo in terms of time to initial pain and maximal walking or absolute
      claudication distance; these findings were confirmed by cilostazol patients'
      positive responses on subscales measuring physical functioning and quality of
      life. In a 24-week randomised double-blind trial in patients with intermittent
      claudication, cilostazol 100mg twice daily produced significant improvements in
      pain-free and maximum walking distances, compared with pentoxifylline
      (oxpentifylline) 400mg 3 times daily and placebo. Cilostazol has been well
      tolerated, with the most common adverse events being headache, diarrhoea,
      abnormal stools and dizziness.

PMID- 10069407
TI  - Behavioural problems associated with dementia: the role of newer antipsychotics.
AB  - Behavioural disorders are a common feature in dementia, especially in the later
      stages of the disease. The most frequent disorders are agitation, aggression,
      paranoid delusions, hallucinations, sleep disorders, including nocturnal
      wandering, incontinence and (stereotyped) vocalisations or screaming. Behavioural
      disorders, rather than cognitive disorders, are the main reason why caregivers
      place patients with dementia in a nursing home. However, although behavioural
      disorders are important, there is still no international agreement with respect
      to the description and definition of symptoms and syndromes. This also holds true
      for the wide variety of scales for quantification and measurement of behavioural
      disorders. Drug therapy should be considered after possible underlying causes
      such as physical illness, drug adverse effects and environmental stressors have
      been ruled out, or specifically addressed, and a behavioural approach has also
      failed. This article briefly reviews the evidence for non-antipsychotic drug
      therapies, which include a variety of substances. However, antipsychotics are the
      group of drugs which have been most frequently studied for the treatment of
      behavioural syndromes in dementia. Drug responsive symptoms include anxiety,
      verbal and physical agitation, hallucinations, delusions, uncooperativeness and
      hostility, whereas wandering, hoarding, unsociability, poor self-care, screaming
      and other stereotyped behaviour seem to be unresponsive to all drugs. Although
      the use of classical antipsychotics is limited by extrapyramidal symptoms,
      anticholinergic adverse effects, sedation and postural hypotension, the newer
      antipsychotics offer the chance of a better risk:benefit ratio. This article
      reviews the small amount of data published on the use of the newer
      antipsychotics, and concludes that risperidone at low dosages (0.5 to 2 mg/day)
      seems to be especially useful for the treatment of behavioural symptoms in
      dementia because of its negligible anticholinergic adverse effects. The use of
      clozapine is limited by its anticholinergic activity, at least in dementia of the
      Alzheimer and Lewy body types. However, in patients with psychosis arising from
      Parkinson's disease it seems to be the drug of choice, and similar activity is
      likely for olanzapine. There are no published data on other newer drugs, such as
      sertindole, quetiapine or ziprasidone. Future studies should also address
      questions of dementia heterogeneity and should compare different drug treatments
      and treatment combinations.

PMID- 10069406
TI  - Limiting neurological damage after stroke: a review of pharmacological treatment
      options.
AB  - Acute ischaemic stroke is a leading cause of death and a major cause of long term
      disability worldwide. Effective treatments for limiting the neurological damage
      after stroke have proven elusive. An improved understanding of the complicated
      cascade of cellular events following the onset of cerebral ischaemia has led to
      exploration of a number of avenues for early intervention. Reperfusion of the
      ischaemic territory using thrombolytic drugs has shown promise in clinical trials
      as a method for achieving tissue salvage. Antithrombotic and antiplatelet agents
      have not demonstrated efficacy as acute therapies, although the early use of
      aspirin (acetylsalicylic acid) appears to produce a reduction in early stroke
      recurrence. A wide variety of drugs which interfere at various points in the
      ischaemic cascade, so-called 'neuroprotective agents', have also been studied,
      but with mixed success. Of these, antagonists of voltage-gated calcium channels,
      antagonists at the N-methyl-D-aspartate (NMDA) receptor and scavengers of free
      radicals have been most extensively studied. Despite proving effective in animal
      models of cerebral ischaemia, these drugs have largely failed to fulfil their
      promise in clinical trials. While individual compounds have proven ineffective,
      combinations of drugs with different mechanisms of action may yet provide the
      best treatment for acute ischaemic stroke.

PMID- 10069410
TI  - Autoreactive human T cell lines recognizing ribosomal protein L7.
AB  - Sera of patients suffering from systemic lupus erythematosus (SLE) frequently
      contain oligoclonal IgG autoantibodies with high affinity for the ribosomal
      protein L7 (rpL7). The humoral autoimmune response to rpL7 apparently is driven
      by antigen and T cell dependent. In order to analyze the T cell response to rpL7
      we cultured peripheral blood lymphocytes of healthy individuals and SLE patients
      in the presence of recombinant rpL7. After 10 days, the cytokine response to re
      stimulation with rpL7 was examined using a spot-ELISA. Measuring IFN-gamma
      secretion, the T cells of two patients and four healthy donors showed a
      significant increase in the number of spots as compared to control cells.
      Secretion of IL-4 or IL-10 was not detected. From the antigen-stimulated primary
      cultures we established by limiting dilution cloning six rpL7-reactive, IFN-gamma
      secreting T cell lines which show a CD3+CD4+CD8- phenotype. One line additionally
      was shown to be positive for HLA-DR and CD45R0, but negative for CD27 and CD31.
      The cell lines carry alphabeta TCR chains which differ from each other in
      sequence and specificity. rpL7 fragments rich in basic amino acids could be
      identified as epitopes recognized by the TCR of three cell lines. Recognition of
      rpL7 is HLA-DR6 restricted or respectively HLA-DP restricted in the two cell
      lines analyzed.

PMID- 10069411
TI  - Induction of CD8+ T cell-mediated protective immunity against Trypanosoma cruzi.
AB  - Trypanosoma cruzi was transformed with the Plasmodium yoelii gene encoding the
      circum-sporozoite (CS) protein, which contains the well-characterized CD8+ T cell
      epitope, SYVPSAEQI. In vivo and in vitro assays indicated that cells infected
      with the transformed T. cruzi could process and present this malaria parasite
      derived class I MHC-restricted epitope. Immunization of mice with recombinant
      influenza and vaccinia viruses expressing the SYVPSAEQI epitope induced a large
      number of specific CD8+ T cells that strongly suppressed parasitemia and
      conferred complete protection against the acute T. cruzi lethal infection. CD8+ T
      cells mediated this immunity as indicated by the unrelenting parasitemia and high
      mortality observed in immunized mice treated with anti-CD8 antibody. This study
      demonstrated, for the first time, that vaccination of mice with vectors designed
      to induce CD8+ T cells is effective against T. cruzi infection.

PMID- 10069412
TI  - Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha
      induced HIV-1 replication in latently infected OM10.1 and Ach2 cells.
AB  - NF-kappaB is a potent cellular activator of HIV-1 gene expression. Down
      regulation of NF-kappaB activation is known to inhibit HIV replication from the
      latently infected cells. Gold compounds have been effectively used for many
      decades in the treatment of rheumatoid arthritis. We previously reported that
      gold compounds, especially aurothioglucose (AuTG) containing monovalent gold ion,
      inhibited the DNA-binding of NF-kappaB in vitro. In this report we have examined
      the efficacy of the gold compound AuTG as an inhibitor of HIV replication in
      latently infected OM10.1 and Ach2 cells. Tumor necrosis factor (TNF)-alpha
      induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by
      non-cytotoxic doses of AuTG (>10 microM in OM10.1 cells and >25 F.M in Ach2
      cells), while 25 microM of the counter-anion thioglucose (TG) or gold compound
      containing divalent gold ion, HAuCl3, had no effect. The effect of AuTG on NF
      kappaB-dependent gene expression was confirmed by a transient CAT assay. Specific
      staining as well as electron microscopic examinations revealed the accumulation
      of metal gold in the cells, supporting our previous hypothesis that gold ions
      could block NF-kappaB-DNA binding by a redox mechanism. These observations
      indicate that the monovalent gold compound AuTG is a potentially useful drug for
      the treatment of patients infected with HIV.

PMID- 10069413
TI  - Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial
      fibroblasts by treatment with aurothioglucose.
AB  - Gold compounds have long been used in the treatment of rheumatoid arthritis (RA).
      However, their actions in RA have not been clarified. In this study, we examined
      the effect of one of the monovalent gold compounds, aurothioglucose (AuTG), on
      the IL-1-induced production of IL-6, IL-8 and granulocyte macrophage colony
      stimulating factor (GM-CSF) from rheumatoid synovial fibroblasts (RSF) isolated
      from three RA patients. IL-6 and IL-8 induction but not GM-CSF induction was
      inhibited in most of the RSF after pretreatment with AuTG. Since gene expression
      of these cytokines is known to be under the control of a common transcription
      factor, NF-kappaB, the effect of AuTG on the cellular localization of NF-kappaB
      (p65 subunit) and on NF-kappaB-DNA binding was examined. Although AuTG treatment
      did not prevent NF-kappaB nuclear translocation, AuTG blocked the DNA-binding
      activity of NF-kappaB when examined in vitro. Morphologically, both metal
      specific cell staining using p-dimethylaminobenzylidene rhodamine and
      transmission electron microscopic examinations demonstrated the accumulation of
      metal gold in the cytoplama and some organella (mitochondria and lysosomes) of
      the AuTG-treated RSF. These results indicate that one of the anti-rheumatic
      actions of AuTG might be through its inhibitory action on NF-kappaB.

PMID- 10069414
TI  - Heterogeneity in the ability of cytotoxic murine NK cell clones to enhance Ig
      secretion in vitro.
AB  - We recently described a panel of cytotoxic murine NK cell clones that also
      enhanced Ig secretion by B cells activated in an in vitro model of T cell
      independent type 2 (TI-2) responses. We employed dextran-conjugated anti-IgD
      (alphadelta-dex) as a model antigen. Here we study the mechanism of Ig induction
      by these clones. Addition of the various NK clones to sort-purified B cells
      stimulated with alphadelta-dex and IL-2 resulted in a markedly heterogeneous
      increase in Ig secretion, which varied from 3-fold, as mediated by clone PKO 56,
      to 15-fold, as induced by clone PKO 101. The other NK cells showed intermediate
      levels of Ig induction. Furthermore, while addition of as few as 0.04% of PKO 101
      cells stimulated significant increases and 1% induced near maximum Ig production,
      a 3% addition of PKO 56 cells was required for significant enhancement of Ig
      secretion. Supernatant material collected from the NK clones mediated Ig
      production at levels that mirrored the induction by the corresponding cells.
      Cytokine analysis showed that while all members of the NK panel produced IFN
      gamma only two secreted granulocyte macrophage colony stimulating factor and that
      the levels of Ig induction mediated by the NK clones correlated only with their
      levels of IFN-gamma secretion. Culture of B and NK cells in the presence of anti
      IFN-gamma demonstrated that IFN-gamma was the critical cytokine in NK-induced Ig
      production. These findings establish heterogeneity in the ability of NK cells to
      increase Ig secretion in vitro and show that NK-produced IFN-gamma is an
      important factor in determining this heterogeneity.

PMID- 10069415
TI  - Differential effects of manipulating signaling in early T cell development in
      intestinal intraepithelial lymphocytes and thymocytes.
AB  - A pre-TCR-CD3 signal is required for the efficient maturation of CD4- CD8-
      thymocytes to the CD4+ CD8+ stage. This study addressed whether a similar signal
      is required for maturation of intestinal intraepithelial lymphocytes (IEL) that
      may develop extrathymically. We have shown previously that IEL from mice
      deficient for CD3- associated zeta chains include an immature population of CD3-
      CD8alphaalpha+ cells expressing cytoplasmic TCR beta chains but lacking
      detectable surface TCRalphabeta, CD16 and B220. Here we stimulated the appearance
      of such IEL in epsilon+/- zeta-/- mice by expression of an activated Lck
      transgene or in vivo treatment with anti-CD3epsilon. Anti-CD3epsilon treatment of
      RAG-deficient animals also yielded CD16- B220- IEL. In contrast, expression of a
      TCRbeta transgene in rag-1(-/-) mice did not stimulate the appearance of CD3-
      CD8alphaalpha+ CD16- B220- cells. Taken together these data indicate that
      although anti-CD3epsilon treatment and LckF505 assist in catalyzing a CD16+ B220+
      --> CD16- B220- transition, these manipulations are not equivalent to a pre-TCR
      signal in IEL lymphocytes.

PMID- 10069416
TI  - The extracellular versus intracellular mechanisms of inhibition of TCR-triggered
      activation in thymocytes by adenosine under conditions of inhibited adenosine
      deaminase.
AB  - The absence or low levels of adenosine deaminase (ADA) in humans result in severe
      combined immunodeficiency (SCID), which is characterized by hypoplastic thymus, T
      lymphocyte depletion and autoimmunity. Deficiency of ADA causes increased levels
      of both intracellular and extracellular adenosine, although only the
      intracellular lymphotoxicity of accumulated adenosine is considered in the
      pathogenesis of ADA SCID. It is shown that extracellular but not intracellular
      adenosine selectively inhibits TCR-triggered up-regulation of activation markers
      and apoptotic events in thymocytes under conditions of ADA deficiency. The
      effects of intracellular adenosine are dissociated from effects of extracellular
      adenosine in experiments using an adenosine transporter blocker. We found that
      prevention of toxicity of intracellular adenosine led to survival of TCR-cross
      linked thymocytes in long-term (4 days) assays, but it was not sufficient for
      normal T cell differentiation under conditions of inhibited ADA. Surviving TCR
      cross-linked thymocytes had a non-activated phenotype due to extracellular
      adenosine-mediated, TCR-antagonizing signaling. Taken together the data suggest
      that both intracellular toxicity and signaling by extracellular adenosine may
      contribute to pathogenesis of ADA SCID. Accordingly, extracellular adenosine may
      act on thymocytes, which survived intracellular toxicity of adenosine during ADA
      deficiency by counteracting TCR signaling. This, in turn, could lead to failure
      of positive and negative selection of thymocytes, and to additional elimination
      of thymocytes or autoimmunity of surviving T cells.

PMID- 10069417
TI  - IgA production in MHC class II-deficient mice is primarily a function of B-1a
      cells.
AB  - Mice deficient in MHC class II expression (C2d mice) do not make antibody to
      protein antigens administered systemically, but their ability to produce IgA
      antibody to antigen administered at mucosal sites has not been described. We
      investigated IgA production by C2d mice and their IgA antibody response to
      antigen given orally. Young C2d mice had normal amounts of serum IgA, intestinal
      secreted IgA and normal numbers of intestinal IgA plasma cells, compared to
      control C57BL/6 mice. IgA production by C2d mice increased with age. Following
      oral immunization with cholera toxin, C57BL/6 mice responded with IgA and IgG
      antibody, and had increased numbers of IgA plasma cells, but C2d mice gave no
      response. The Peyer's patch and mesenteric lymph node tissues of C2d mice
      contained very few CD4-expressing T cells. Thus, C2d mice have no typical mucosal
      CD4 Th cells and cannot respond to a strong oral immunogen, yet they still
      produced and secreted IgA. We hypothesized that B-1 lymphocytes could provide a
      source of IgA independent of antigen-specific T cell help. Young C2d mice had
      normal numbers of peritoneal B-1a cells and their frequency increased with age.
      To test the role of these B-1a cells, we bred C2d mice to obtain mice that had no
      MHC class II expression and expressed the Xid gene that confers deficiency in B
      1a cells. These double-deficient mice had 10-fold less serum and secreted IgA
      than all other F2 littermates. We conclude that B-1a cells are essential for the
      majority of IgA production in C2d mice. Thus, the C2d mouse may provide a useful
      tool for analysis of the role of intestinal IgA provided by B-1a cells.

PMID- 10069418
TI  - Fc receptor beta subunit is required for full activation of mast cells through Fc
      receptor engagement.
AB  - The high-affinity IgE receptor (Fc epsilonRI) and the low-affinity IgG receptor
      (Fc gammaRIII) on mast cells are the key molecules involved in triggering the
      allergic reaction. These receptors share the common beta subunit (FcRbeta) which
      contains an immunoreceptor tyrosine-based activation motif and transduces the
      signals of these receptors' aggregation. In rodents, FcRbeta is essential for the
      cell surface expression of the Fc epsilonRI. In humans, the FcRbeta gene was
      reported to be one of the candidate genes causing atopic diseases. However, the
      role of FcRbeta in vivo still remains ambiguous. To elucidate the functions of
      FcRbeta, we developed the mice lacking FcRbeta [FcRbeta(-/-)]. The FcRbeta(-/-)
      mice lacked the expression of the Fc epsilonRI on mast cells and IgE-mediated
      passive cutaneous anaphylaxis (PCA) was not induced in FcRbeta(-/-) mice as was
      expected. In these mice, the expression of IgG receptors on mast cells was
      augmented but the IgG-mediated PCA reaction was attenuated. Although with bone
      marrow-derived cultured mast cells from FcRbeta(-/-), adhesion to fibronectin and
      Ca2+ flux upon aggregation of IgG receptors were enhanced, mast cells co-cultured
      with 3T3 fibroblasts exhibited impaired degranulation on receptor aggregation.
      These observations indicate that FcRbeta accelerates the degranulation of mature
      mast cells via the IgG receptor in connective tissues.

PMID- 10069419
TI  - Characterization of the culture filtrate-specific cytotoxic T lymphocyte response
      induced by Bacillus Calmette-Guerin vaccination in H-2b mice.
AB  - Although CD8+ T cells are supposed to play an important role in protective
      immunity to mycobacteria, cytotoxic T lymphocyte (CTL) responses in this
      infection remain poorly characterized. We previously demonstrated that bacillus
      Calmette-Guerin (BCG) immunization of H-2b mice induced CTL able to recognize and
      kill macrophages incubated with proteins from mycobacterial culture supernatant
      [culture filtrate (CF) antigens]. In the present study, we have further
      characterized the lytic activity of these CTL and the processing pathway used for
      the presentation of CF proteins. We show that they use the degranulation pathway
      (secretion of perforins and granzymes) as the main lytic mechanism of
      cytotoxicity and also secrete IFN-gamma upon incubation with CF-pulsed
      macrophages. The in vitro presentation of CF proteins to CTL required a
      processing step inhibited in the cold but insensitive to Brefeldin A. Transporter
      associated protein (TAP)-2-deficient RMA-S cells were efficiently recognized and
      killed by CF-specific CTL, demonstrating the lack of TAP requirement for this
      presentation. However, recognition of target cells by CTL was abolished when
      carried out in the presence of chloroquine. These results indicate that a non
      classical MHC class I-processing pathway allows the recognition of a CF protein
      by CTL in BCG-vaccinated H-2b mice.

PMID- 10069420
TI  - Mechanisms of acute inflammatory lung injury induced by abdominal sepsis.
AB  - Sequestration of neutrophils and release of histotoxic mediators are considered
      important for the development of pathologic alterations of the lung defined as
      adult respiratory distress syndrome. Mechanisms of inflammatory lung injury
      caused by abdominal sepsis were investigated using the colon ascendens stent
      peritonitis (CASP) model that closely mimics the human disease. In the CASP
      model, a continuous leakage of intraluminal bacteria into the peritoneal cavity
      is induced by implantation of a stent in the ascending colon, generating a septic
      focus. In contrast to the cecal ligation and puncture model of peritonitis,
      survival of mice following CASP surgery is dependent on IFN-gamma, but
      independent of tumor necrosis factor (TNF). Here we show that the systemic
      inflammation induced by CASP surgery results in a rapid and profound increase of
      lung vascular permeability that was associated with the activation and
      recruitment of neutrophils to the lung. Activation of circulating granulocytes
      was characterized by increased production of serine proteinases and reactive
      oxygen metabolites, as well as elevated expression of cell surface Mac-1.
      Expression of MIP-2, KC, MIP-1alpha and E-selectin mRNA in lung was strongly
      increased within 3 h following CASP surgery, whereas up-regulation of IP-10, MCP
      1 and P-selectin was delayed. In contrast, induction of RANTES, LIX, ICAM-1 and
      VCAM-1 mRNA was weak or not detectable after CASP surgery. Importantly,
      recruitment of leukocytes to the lung was normal in lipopolysaccharide-resistant
      mice, and was not affected by antibody neutralization of TNF or the chemokines
      MIP-2 and KC.

PMID- 10069421
TI  - Differentiation of human CD8 T cells: implications for in vivo persistence of
      CD8+ CD28- cytotoxic effector clones.
AB  - CD8 T cells contain a distinct subset of CD8+ CD28- cells. These cells are not
      present at birth and their frequency increases with age. They frequently contain
      expanded clones using various TCRalphabeta receptors and these clones can
      represent >50% of all CD8 cells, specially in old subjects or patients with
      chronic viral infections such as HIV-1. Herein, it is shown that a large fraction
      of CD8+ CD28- cells expresses intracellular perforin by three-color flow
      cytometry, in particular when this subset is expanded. Together with their known
      ability to exert potent re-directed cytotoxicity, this indicates that CD8+ CD28-
      T cells comprise cytotoxic effector cells. With BrdU labeling, we show that CD8+
      CD28- cells derive from CD8+ CD28+ precursors in vitro. In addition, sorted CD8+
      CD28+ cells gave rise to a population of CD8+ CD28- cells after allo-stimulation.
      Moreover, ex vivo CD8+ CD28+ cells contain the majority of CD8 blasts, supporting
      the notion that they contain the proliferative precursors of CD8+ CD28- cells.
      CD95 (Fas) expression was lower in CD8+ CD28- cells, and this subset was less
      prone to spontaneous apoptosis in ex vivo samples and more resistant to
      activation-induced cell death induced by a superantigen in vitro. Thus, the
      persistence of expanded clones in vivo in the CD8+ CD28- subset may be explained
      by antigen-driven differentiation from CD8+ CD28+ memory precursors, with
      relative resistance to apoptosis as the clones become perforin(+) effector cells.

PMID- 10069422
TI  - Marking IL-4-producing cells by knock-in of the IL-4 gene.
AB  - IL-4 is a cytokine which can be expressed by a number of cell types including Th2
      cells, mast cells and a population of CD4+ NK1.1+ NK T cells. Although phenotypic
      markers exist for identifying each of these cell types, there is at present no
      known cell surface marker common to all IL-4-producing cells. Using gene
      targeting in embryonic stem cells, we have modified the IL-4 locus by knock-in of
      a transmembrane domain to generate mice that express a membrane-bound form of IL
      4 (mIL-4). Flow cytometry using an IL-4-specific mAb allowed the detection of IL
      secreting Th2 cells, mast cells and NK T cells from mIL-4 mice. Furthermore, the
      analysis of immune responses in mIL-4 mice following immunization with anti-CD3
      and anti-IgD has allowed us to identify distinct subpopulations of IL-4-producing
      NK T cells. Thus, the expression of IL-4 in a membrane-bound form provides a
      novel method for the identification and characterization of IL-4-producing cells.

PMID- 10069423
TI  - MHC class II gene associations with autoantibodies to U1A and SmD1 proteins.
AB  - Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequently
      present in the serum of patients with systemic rheumatic diseases, and have been
      reported to be associated with HLA-DR and -DQ genes. To better define the role of
      HLA genes in the production of such antibodies, we studied immunogenetic
      associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and
      synthetic peptides containing immunodominant linear epitopes of these proteins.
      Only two out of the 15 overlapping peptides of U1A (i.e. peptides 35-58 and 257
      282) and three of 11 peptides of SmD1 (i.e. peptides 1-20, 44-67 and 97-119) were
      significantly recognized by patients' sera selected on the basis of their
      antibody positivity with RNP in immunodiffusion. The distribution of DRB1, DQB1
      and DPB1 alleles among the anti-RNP antibody-positive patients (n = 28) and
      healthy control subjects was similar. Antibodies against U1A (tested in Western
      immunoblotting with HeLa cell extracts) were positively associated to DRB1*06
      allele; antibodies reacting with SmD1 peptide 44-67 were negatively associated to
      DRB1*02 and DQB1*0602 alleles. No association was found between DPB1 alleles and
      antibodies reacting with U1A and SmD1 antigens. This first study reporting an
      association between autoantibodies reacting with U1A and SmD1 proteins (and
      peptides of these proteins), and immunogenetic markers suggest that the
      production of antibody subsets directed against different components (or regions
      of these proteins) bound to the same snRNP particle is associated with distinct
      MHC class II alleles.

PMID- 10069424
TI  - Core 2-containing O-glycans on CD43 are preferentially expressed in the memory
      subset of human CD4 T cells.
AB  - Human CD4 T cells can be divided into two functionally distinct subsets: a
      CD45RO+ memory subset and a CD45RA+ naive subset. In an attempt to identify novel
      cell surface molecules on these cells, we have developed a mAb, anti-1D4. The
      antigen defined by anti-1D4 was preferentially expressed on the memory subset of
      freshly isolated peripheral CD4 T cells and 1D4+ CD4 T cells functionally
      corresponded to memory T cells. Retrovirus-mediated expression cloning revealed
      that the 1 D4 antigen is human CD43. Transfection of CHO-leu cells, which stably
      express human CD43, with core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT)
      conferred expression of the 1D4 antigen and mRNA of C2GnT was detected by RT-PCR
      only in 1D4+ T cells but not in 1D4- T cells, implying that the 1 D4 antigen is
      composed of core 2-containing O-glycans on CD43. Reactivity with anti-1 D4 was
      completely abolished when cells were treated with neuraminidase, while them
      remained weak binding of anti-T305, a previously described mAb which also reacts
      with CD43 modified with core 2-containing O-glycans. Moreover, anti-1D4 markedly
      reacted with NIH-3T3 cells expressing human CD43 and low levels of endogenous
      C2GnT, whereas anti-T305 reacted slightly. These results indicate that the 1D4
      antigen is distinct from the epitope defined by anti-T305 and anti-1D4 is a more
      sensitive probe to detect core 2-containing O-glycans than anti-T305. Taken
      together, our results indicate that core 2-containing O-glycans, whose expression
      can easily be detected with anti-1D4, are preferentially expressed in the CD45RO+
      memory subset of CD4 T cells.

PMID- 10069425
TI  - HLA-DM and invariant chain are expressed by thyroid follicular cells, enabling
      the expression of compact DR molecules.
AB  - Thyroid follicular cells (TFC) in Graves' disease (GD) hyperexpress HLA class I
      and express ectopic HLA class II molecules, probably as a consequence of
      cytokines produced by infiltrating T cells. This finding led us to postulate that
      TFC could act as antigen-presenting cells, and in this way be responsible for the
      induction and/or maintenance of the in situ autoimmune T cell response. Invariant
      chain (li) and HLA-DM molecules are implicated in the antigen processing and
      presentation by HLA class II molecules. We have investigated the expression of
      these molecules by TFC from GD glands. The results demonstrate that class II+ TFC
      from GD patients also express li and HLA-DM, and this expression is increased
      after IFN-gamma stimulation. The level of HLA-DM expression by TFC was low but
      sufficient to catalyze peptide loading into the HLA class II molecules and form
      stable HLA class II-peptide complexes expressed at the surface of TFC. These
      results have implications for the understanding of the possible role of HLA class
      II+ TFC in thyroid autoimmune disease.

PMID- 10069426
TI  - Type I IFN sets the stringency of B cell repertoire selection in the bone marrow.
AB  - Locally produced type I interferon (IFN-I) enhances the sensitivity of bone
      marrow B cell to IgM receptor ligation. The establishment of B cell repertoires,
      on the other hand, seems to involve selective processes that are critically
      dependent on B cell receptor (BCR) ligation. In order to assess the importance of
      BCR triggering thresholds on the selection of polyclonal unmanipulated B cell
      populations, we compared VH gene expression and reactivity repertoires in various
      B cell compartments of wild-type and IFN-I receptor-deficient mice (IFN-I-R-/-).
      These analyses demonstrate that increased B cell sensitivity to BCR ligation
      mediated by IFN-I in the bone marrow (BM) has consequences on the stringency of B
      cell repertoire selection. Thus, the normal counter-selection of both VH7183 gene
      family expression and multireactivity was impaired among immature BM B cells from
      mutant mice. Furthermore, as a result of reduced efficiency of BCR ligation
      dependent inhibition of terminal differentiation, IFN-I-R-/- animals produce, in
      BM and thymus, higher numbers of plasma cells secreting antibodies that are more
      multireactive than wild-type animals. Finally, mutant serum IgM natural
      antibodies display a more reactive repertoire than controls, a likely reflection
      of the BM resident plasma cell repertoire. The present observations demonstrate,
      therefore, that local modulation of BCR triggering thresholds leads to important
      modifications in the generation and/or selection of normal B cell populations.

PMID- 10069427
TI  - Non-coding plasmid DNA induces IFN-gamma in vivo and suppresses autoimmune
      encephalomyelitis.
AB  - Regulatory sequences used in plasmids for naked DNA vaccination can modulate
      cytokine production in vivo. We demonstrate here that injection of plasmid DNA
      can suppress the prototypic T cell-mediated autoimmune disease, experimental
      autoimmune encephalomyelitis, by inducing IFN-gamma.

PMID- 10069428
TI  - Evidence for suppressed activity of the transcription factor NFAT1 at its
      proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4
      gene transcription in T cells of atopic patients.
AB  - Allergen-specific T cells in atopic patients are polarized IL-4-producing Th2
      cells, promoting IgE synthesis by B cells. The molecular basis for increased IL-4
      gene expression in atopy is not fully understood. IL-4 gene regulation in general
      involves the nuclear factor of activated T cells (NFAT) family of transcription
      factors, of which NFAT1 and NFAT2 are most prominent in peripheral T cells.
      Recently, a unique inhibitory role of NFAT1 in IL-4 gene control was shown in the
      mouse. In a series of electrophoretic mobility shift assays with protein extracts
      of highly polarized Th2 clones from atopics and Th1 clones from controls we
      compared DNA-binding activities at the two NFAT-binding elements P0 and P1 of the
      crucial proximal human IL-4 promoter. At the most proximal P0 site, NFAT
      containing complexes devoid of NFAT2 were readily inducible in the Th1 clones,
      but hardly or not in the Th2 clones. In contrast, both in Th1 and Th2 clones NFAT
      containing complexes were strongly inducible at the P1 site, consisting of NFAT2
      and a P0-compatible NFAT activity, without apparent differences between Th1 and
      Th2 clones. Like in Th2 clones, suppressed NFAT-P0 complex formation was observed
      also at the polyclonal level in peripheral blood mononuclear cells (PBMC) of
      three of five severe atopic dermatitis patients with strongly elevated serum IgE
      levels, but not in control PBMC. These findings suggest that high-level IL-4
      production in atopic Th2 cells is associated with selective reduction of
      suppressive NFAT1 activity at the IL-4 P0 element and that some patients with
      this multifactorial disease may have a putative systemic disorder at this level.

PMID- 10069429
TI  - Release and preparation of intact and unreduced N-linked oligosaccharides from Sf
      9 insect cells.
AB  - Glycosylation, the addition of carbohydrates to a peptide backbone, is the most
      extensive cotranslational and posttranslational modification made to proteins by
      eukaryotic cells. The glycosylation profile of a recombinant glycoprotein can
      significantly affect its biological activity, which is particularly important
      when being used in human therapeutic applications. Therefore, defining glycan
      structures to ensure consistency of recombinant glycoproteins among different
      batches is critical. In this study we describe a method to prepare N-linked
      glycans derived from insect cell glycoproteins for structural analysis by
      capillary electrophoresis. Briefly, glycoproteins obtained from uninfected
      Spodoptera frugiperda Sf-9 insect cells were precipitated with ammonium sulfate
      and the glycans were chemically cleaved by hydrazinolysis. Following the
      regeneration of the glycan reducing terminal residue and the removal of
      contaminating proteins and peptides, the glycans were fluorescently labeled by
      reductive amination. Fluorescent labeling greatly enhanced the detection limit of
      the glycan structures determined by capillary electrophoresis. Five major glycan
      structures were found that migrated between tetra-mannosylated hexasaccharide and
      nonamannosylated undecasaccharide standards. Upon alpha-mannosidase digestion the
      number of glycan structures was reduced to two major structures with shorter
      migration times than the undigested glycans. None of the glycans were susceptible
      to hexosaminidase or galactosidase treatment. These results are consistent with
      the majority of previous results demonstrating hypermannosylated glycan
      structures in Sf-9 insect cells.

PMID- 10069430
TI  - Isolation of a proliferation inhibitor factor from uterine myomatosis
      fibroblasts.
AB  - In this work, we report the isolation of a factor from the culture supernatant of
      confluent fibroblasts from human cervix with the diagnosis of uterine myomatosis.
      This factor possesses the capacity to inhibit the proliferation of normal
      fibroblasts. The proliferation inhibitor factor (PIF) was purified from the
      culture supernatant by precipitation with 80% ammonium sulfate, and by molecular
      sieve chromatography. Our results indicate that PIF is a protein of 23 kDa, which
      is highly sensitive to trypsin treatment, and is thermolabile, since temperatures
      equal to, or above, 60 degrees C eliminate the protein activity in 15 to 20 min.
      Western blot analyses identified no cross reactions of the purified PIF with TGF
      alpha, TNFalpha, IFNgamma, or IL-1beta, suggesting that PIF is a new protein
      belonging to the group of factors secreted by fibroblasts able to inhibit
      cellular proliferation.

PMID- 10069431
TI  - A single step purification process for cyclodextrin glucanotransferase from a
      Bacillus sp. isolated from soil.
AB  - Cyclodextrin glucanotransferase (CGTase) is a commercially important enzyme which
      catalyses the formation of cyclodextrins (CDs) from starch. A CGTase producing
      bacterium was isolated from soil which gave a fairly high enzyme activity of 7.5
      U mL(-1) after 24 h of growth which was further increased to 22 U mL(-1) by
      proper media design. The enzyme was purified to homogeneity by a novel single
      affinity precipitation step which resulted in a very high recovery of more than
      90%. The molecular weight, as determined by SDS-PAGE, was found to be 68 kDa. The
      pH optimum was found to be 6.6 while a temperature optimum of 65 degrees C was
      observed. The enzyme exhibited a fairly high degree of functional stability with
      little loss of activity, even after 8 h of incubation at 65 degrees C. Ca++ had
      little effect on the activity of the enzyme while urea at 10 mM concentration
      increased the activity of the enzyme by more than 200%, suggesting that it is a
      unique enzyme.

PMID- 10069432
TI  - An improved alkaline lysis method for minipreparation of plasmid DNA.
AB  - This study is to improve the digestion pattern of miniprepped plasmid analyzed on
      gel. Frequently, some ambiguous DNA bands, which are suspected to be denatured
      DNA molecules, appear during electrophoresis of enzyme digested miniprepped
      plasmids. By employing Southern hybridization of two identical gels, one had been
      treated with denaturation-neutralization step and another without such treatment,
      we confirmed that many of these ambiguous DNA bands were single-stranded (SS) DNA
      molecules. The presence of SS DNA was due to the use of excess amount of NaOH
      during plasmid DNA purification with the conventional alkaline lysis method. We,
      therefore, modified the procedure and recommend that a half amount of NaOH (0.1N
      instead of 0.2N) should be used when isolating small quantity of plasmid DNA with
      the method.

PMID- 10069433
TI  - Biosensor for the enantioselective analysis of S-perindopril.
AB  - Because S-perindopril enantiomer is the eutomer which is responsible for the
      angiotensin-converting enzyme inhibition activity, it is necessary to develop a
      reliable method for its assay from its distomer, the R-enantiomer. For this
      purpose, an amperometric biosensor was developed based on L-amino acid oxidase.
      The working range of the described biosensor was 20pmol/L-10 micromol/L on the
      7.0-7.4 pH range, with a detection limit of 2pmol/L. The low enantioselectivity
      for R-perindopril, as compared with S-enantiomer, was demonstrated by both mixed
      solutions and separate solutions methods (amperometric selectivity coefficient is
      1.0 x 10(-4)). The biosensor was also selective towards D-proline and
      polyvinylpyrrolidone. The amperometric biosensor can be used for enantioselective
      analysis of S-perindopril in raw material, with an RSD < 1%. The life time (t95%)
      of the biosensor is three weeks.

PMID- 10069434
TI  - Method for the isolation and purification of pyridinoline and deoxypyridinoline
      crosslinks from bone by liquid chromatographic techniques.
AB  - Significant progress has been made in recent years in the development of new bone
      resorption markers, based principally on the urinary excretion of pyridinoline
      (Pyd) and deoxypyridinoline (Dpd) crosslinks. For their measurement, in spite of
      the recent development of immunoassays, HPLC remains the method of reference.
      However, the lack of an appropriate internal standard requires large amounts of
      pure crosslinks for external standardisation. Herein, we describe an efficient
      method for the isolation of both crosslinks from bone of adult turkey by
      isocratic semi-preparative HPLC. Demineralized bone is hydrolysed in hydrochloric
      acid, 9 M. A first liquid extraction step in butanol allowed to eliminate less
      polar compounds. The aqueous phase was concentrated and separated by gel
      filtration on Biogel P2 and eluted by acetic acid solution (10%). Fractions
      containing pyridinoline were pooled, concentrated, and purified on a CF1
      cellulose column. Pyd and Dpd crosslinks were then separated isocratically by
      HPLC on a C18 reversed phase column (Vydac 218 TP 1010, 250x10 mm) and eluted
      with HFBA as the ion-pairing agent. Retention times of Pyd and DPD were 23.6 and
      28.7 min, respectively. Both crosslinks prepared by HPLC were then transformed as
      hydrochloride to cellulose phosphate and desalted on Sephadex G-10 columns. These
      two further steps yielded highly purified compounds (the purity was greater than
      98% evaluated by aminoacid analysis). In conclusion, the efficiency of this
      method allows to obtain rapidly Pyd and Dpd without interfering compounds as
      proven by spectral studies (NMR and mass spectroscopy).

PMID- 10069435
TI  - Prokaryotic gene fusion expression systems and their use in structural and
      functional studies of proteins.
AB  - The ability to express and purify large quantity of proteins in bacteria has
      greatly impacted many aspects of biological research. These include their use as
      a source of reagent for biochemical and biophysical studies as well as a source
      of antigen for antibody production. Currently many different expression systems
      are available and new ones are being developed. These systems allow inducible
      expression of a desired protein as a fusion with an affinity tag for simple
      purification. The affinity tags can generally be removed by specific proteases
      which recognize cleavage sites engineered between the affinity tag and the
      desired protein. Presence of tags that encode epitopes of specific antibodies
      provide additional means for identification of recombinant proteins. This review
      provides an overview of some of the most commonly utilized expression systems and
      examples of the use of these proteins in biochemical and biophysical studies. I
      will also describe other available systems which may provide suitable alternative
      for expression of recombinant proteins.

PMID- 10069436
TI  - Preparation of a genomic library using a TA vector.
AB  - An efficient and simple method for constructing a genomic DNA library is
      presented using a TA cloning vector. It is based on sonication cleavage of
      genomic DNA, blunting of the fragment ends with mung bean nuclease, and addition
      of a single 3'-deoxyadenylate with Taq DNA polymerase, followed by ligation with
      a TA vector. This method is useful for improving the quality of genomic libraries
      for organisms whose genomic DNA is not well digested with restriction enzymes
      owing to the presence of polysaccharides and/or DNA methylation.

PMID- 10069437
TI  - Maternal and developmental toxicity of halogenated 4'-nitrodiphenyl ethers in
      mice.
AB  - In an ongoing effort to delineate structure-activity relationships in the
      developmental toxicity of diphenyl ethers, we evaluated the maternal and
      developmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen.
      All possible trichlorophenyl 4'-nitrophenyl ethers were evaluated, as were the
      2,4-difluorophenyl and 2,4-dibromophenyl 4'-nitrophenyl ethers. We also evaluated
      bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl congeners with meta
      substituents on the 4'-nitrophenyl ring. Nitrofen (2,4-dichlorophenyl 4'
      nitrophenyl ether) was included for comparison. Identity of the halogen affected
      the postnatal (but not prenatal) mortality induced by 2,4-dihalogenated 4'
      nitrophenyl ethers. The presence of 3'-substituents on the 4'-nitrophenyl ring
      reduced both pre- and postnatal toxicity of 2,4-dichlorinated congeners. Among
      chlorinated 4'-nitrophenyl congeners without meta-substituents on the nitrophenyl
      ring, the position of chlorine substituents strongly affected the congener's
      potential for inducing prenatal vs. postnatal syndromes. All congeners increased
      liver to body weight ratios in unmated females, but such increases were not well
      correlated with either prenatal or postnatal embryotoxicity.

PMID- 10069438
TI  - Teratological interaction between the bis-triazole antifungal agent fluconazole
      and the anticonvulsant drug phenytoin.
AB  - Previous studies implicated the cytochrome P450 (CYP) system as critical in the
      teratogenic bioactivation of phenytoin (PHT). Fluconazole (FCZ) is an antifungal
      bis-triazole with potent inhibitory effect on the principal CYP-dependent
      metabolic pathway of PHT. In this study an in vivo experimental model was used to
      evaluate the potential ability of FCZ (2, 10, or 50 mg/kg intraperitoneally) to
      modulate PHT (65 mg/kg intraperitoneally) teratogenesis on day 12 (plug day = day
      1) Swiss mice. PHT alone elicited embryocidal and malformative effects, with
      cleft palate as the major malformation. Pretreatment with the nonembryotoxic
      dosage of 10 mg FCZ/kg potentiated PHT-induced teratogenesis, as indicated by a
      twofold (from 6.2% to 13.3%) increment of cleft palate incidence (P < 0.05).
      Combined treatment with 50 mg FCZ/kg plus PHT resulted in a statistically
      significant (P < 0.05) increment of the resorption incidence recorded after PHT
      alone exposure, but possibly as a consequence of the increased embryolethality,
      in the loss of the potentiative effect on PHT teratogenesis. Although the
      mechanistic nature of teratological interaction between FCZ and PHT remains to be
      established, these results may not support CYP system-mediated metabolic
      conversion as the mechanistic component of PHT teratogenesis.

PMID- 10069439
TI  - Development of a morphologically-based scoring system for postimplantation New
      Zealand White rabbit embryos.
AB  - Rodent whole-embryo culture (WEC) systems are well-established, as are several
      corresponding morphological scoring systems. Recently, WEC techniques for rabbits
      have been developed, creating the need for a morphological evaluation system in
      this species. Consequently, we developed a gestational-age-based quantitative
      morphology evaluation system for rabbit embryos. Detailed descriptions of 21
      embryonic structures, as collected from gestational day (gd) 9-13 rabbit embryos,
      formed the basis for this evaluation system. These descriptions were then
      developed into specific criteria for assigning numerical scores to quantify the
      degree of development of each embryonic structure. The overall morphologic score
      was calculated as the average of the individual structure scores. To make the
      system as informative as possible, the numerical scale of the scoring system was
      gestationally age-based (i.e., range of potential scores was 9.0-13.0). The
      scoring system was then applied in the evaluation of New Zealand White (NZW)
      rabbit embryos explanted on gd 9 and cultured for 48 hr. Embryos grown in vitro
      developed normally, but at a slightly slower rate in vitro than in vivo, as
      evidenced by the lower morphology score (10.4 in vitro, 11.0 in vivo) and
      measures of growth (somite number, total protein, and head length). This work
      firmly establishes the normal archetype of embryonic development in the gd 9-13
      NZW rabbit and provides an important tool for the advancement of mechanistic
      studies of rabbit embryos developing both in vivo and in vitro.

PMID- 10069440
TI  - Evaluation of various toxicants in rabbit whole-embryo culture using a new
      morphologically-based evaluation system.
AB  - In an effort to advance the use of whole-embryo culture (WEC) techniques in the
      rabbit, we recently developed a gestational-age-based quantitative morphologic
      evaluation system for rabbit embryos. In the current study, we applied this new
      morphological scoring system to assess the development of rabbit gestational day
      (gd) 9 embryos exposed for 48 hr in WEC to the teratogens ethanol (EtOH, 154 mM),
      6-aminonicotinamide (6AN, 0.15 mM), and methoxyacetic acid (MAA, 5.0 mM), and the
      nonteratogen penicillin G (PG, 2.0 mM). Each teratogen at the concentration
      tested markedly inhibited morphological development, as indicated by
      significantly lower morphologic scores (10.1+/-0.05, EtOH; 10.2+/-0.05, 6AN; and
      9.8, MAA) relative to controls (10.6+/-0.04), and resulted in an increased
      percentage of malformed embryos (53%, EtOH; 57%, 6AN; 90%, MAA; and 3%, control).
      Embryonic growth, as measured by head length, somite number, and total embryonic
      protein, was significantly decreased by each teratogen. The abnormalities
      produced by teratogen exposure, which included brain, somite, and facial defects,
      were often similar to those produced following in vivo exposure in rabbits and
      rodents, and/or in vitro exposure in rodents. In contrast to the teratogen
      exposure groups, PG had no effect on embryo growth parameters, or on malformation
      rate (6%), although a slight but statistically significant decrease in morphology
      score (10.5+/-0.03) was noted. Our preliminary studies demonstrate the usefulness
      of the morphology evaluation system by quantifying graded differences in
      development, and indicate that rabbit WEC may be a useful adjunct to rodent WEC
      in gaining insights regarding differential interspecies sensitivity.

PMID- 10069441
TI  - Morphological alterations induced by sodium valproate on somites and spinal
      nerves in rat embryos.
AB  - The antiepileptic drug valproic acid is a well-known teratogenic agent; its main
      target organ is the neural tube, though skeletal malformations have also been
      described. In our recent work, respecifications of vertebrae were described in
      rat fetuses after treatment with 400 mg/kg of sodium valproate at specific
      somitogenic stages. The observed malformations were stage-dependent.
      Morphological segmental respecification was observed at the level of segments in
      formation at the moment of exposure and at the level of more posterior segments.
      Recently, specific alterations in the development of cranial nerves and ganglia
      were described in mouse embryos after in vitro exposure to VPA. The aim of the
      present work was to analyze dysmorphogenetic effects of VPA on embryonic
      metameric structures: somites, spinal and cranial nerves, and ganglia. Sodium
      valproate (400 mg/kg) was subcutaneously injected at specific gestational times
      corresponding to embryonic stages: presomitic or at about 2, 6, 10, 14, 18, or 22
      somites. Females were sacrificed on the day 12 post coitum, and embryos were
      examined. Morphological examination of somites was performed by staining with
      acridine orange. Morphological examination of nerves and ganglia was performed by
      immunostaining, using monoclonal antibodies to the 160-kD neurofilament protein.
      No abnormalities were observed in the cranial nerves and ganglia. Specific and
      stage-dependent alterations were observed both at the level of the somites and at
      the level of the spinal nerves. The following characteristic malformations were
      observed: fusions, duplications, and reductions of somites and corresponding
      spinal nerves and ganglia. Our morphological data suggest a morphogenetic action
      of VPA at the level of the axial segments, with a possible respecification of the
      identity of the interested segments and their derivatives.

PMID- 10069442
TI  - Teratology Society 1998 Public Affairs Committee Symposium: the new thalidomide
      era: dealing with the risks.

PMID- 10069443
TI  - BCL-2--general considerations.
AB  - BCL-2 protein is a oncoprotein considered to have an important role in the
      regulation of programmed cell death--apoptosis. The intracellular localization,
      the relation with other oncoproteins, the antioxidant function and the
      pathological implications are discussed.

PMID- 10069444
TI  - P53, p15INK4B, p16INK4A and p57KIP2 mutations during the progression of chronic
      myeloid leukemia.
AB  - The occurrence of acute transformation during the treatment of chronic myeloid
      leukemia (CML) is still a poorly understood mechanism. In this disease p53,
      p16INK4A, p15INK4B, p57KIP2 mutations and p15INK4B/p16INK4A homo/hemizygous
      deletions were analyzed in the initial diagnosis phase and during the treatment
      phase of twelve CML cases, in order to establish whether there was a consistent
      molecular genetic alteration in its progression. During the treatment period,
      four of twelve cases had blastic crisis. All the mutations observed in p53,
      p16INK4A and p15INK4B cumulated in three out of four CML cases who had blastic
      crises. In one case, p53 codon 282 mutation (CGG-->TGG; arg-->trp) were observed
      in initial diagnosis. Seven months later, G-->C transition in the 3' side of p15
      cDNA (778. nucleotide) was observed in the accelerated phase with the same p53
      codon 282 mutation. Thirteen months later, this patient died as a result of
      blastic crisis. The patient in blastic crises in the initial diagnosis phase had
      a mis-sense point mutation in p16 codon 69 (ACT-->AGT; thr-->ser) and a
      polymorphism in codon 68 (GCC-->GCG). Six months later, this patient also died.
      In one case, p53 codon 237 mutation (ATG-->ATA; met-->ile) were observed in the
      initial diagnosis phase. Then months later, the patient died as a result of
      blastic crises. No p15INK4B/p16INK4A homo/hemizygous deletion and p57KIP2 gene
      mutation which was described in the same pathway were observed in CML
      progression. These results indicate that p15INK4B and p16INK4A gene alterations
      may have an affect on the progression of CML-like p53 mutation. A correlation was
      found with the progression of CML and p53, p15INK4B and p16INK4A somatic
      mutations. Finding p15INK4B and p16INK4A gene alteration as well as p53 mutations
      may be a prognostic marker in patients with CML.

PMID- 10069445
TI  - Cloning and characterization of bone marrow cells from patients with acute
      lymphoid leukemia (ALL) in agar cultures.
AB  - Acute lymphoid leukemias (ALL) represent malignant clonal expansions of lymphoid
      hemopoietic cells arrested at different stages of B- or T-cell maturation. We
      studied surface marker profiles and cloning capability of bone marrow (BM) cells
      from 22 adult ALL-patients at diagnosis (n = 15) or relapse (n = 7) in agar
      cultures under different culture conditions in order to develop a screening
      system for the classification of ALL and the detection of residual leukemia.
      Immunophenotyping of those 22 BM-samples enabled a classification in B- or T
      linear ALL. Colony growth of BM-cells could be obtained in four out of 20 cases
      of ALL at diagnosis and in one case at relapse. Different stimulating factors and
      their combinations (GM-CSF; IL-1; IL-2; IL-3; IL-4; IL-6; placenta conditioned
      media (PCM); Phytohemagglutinin (PHA, 40%) and lipopolisaccaride (LPS, 1.25%)-
      containing conditioned media ('B-ly'); IL-1+IL-3; IL-1+IL-4; IL-1+IL-6; IL-1+B
      ly) did not show an overall significant difference in stimulating ALL-clones.
      Immunological phenotyping of ALL-clones in these 5 cases could prove the lymphoid
      leukemic character of the clones obtained. CONCLUSIONS: Our data show that colony
      growth of ALL-BM-cells is difficult. Nevertheless, in cases where colony growth
      could be obtained those clones showed the original surface marker profile of the
      leukemic cells proving the specificity of our colony assay.

PMID- 10069446
TI  - Role of lipids, lipoproteins and lipid peroxidation in thrombocytopenia in
      patients with vivax malaria.
AB  - Possible roles of oxidative and metabolic changes of lipids in the development of
      thrombocytopenia in patients with vivax malaria were investigated. Serum total
      cholesterol, HDL and LDL cholesterols, triglycerides, lipid peroxidation level
      and platelet counts were determined in 60 patients with vivax malaria and
      compared with 50 healthy individuals. Inter-relationships of parameters were
      investigated. In patients, serum total cholesterol, HDL and LDL cholesterol
      concentrations and platelet counts were lower, and serum triglycerides and plasma
      lipid peroxidation concentrations were higher than those of control subjects.
      Significant relationships were found among serum lipid parameters, plasma lipid
      peroxidation and thrombocyte counts. Decrease in total cholesterol, HDL and LDL
      cholesterols and platelet counts may be related or secondary to oxidative stress.
      In the treatment of thrombocytopenia required in the some cases of malaria, the
      supplementation of antioxidative vitamins may be considered.

PMID- 10069447
TI  - Analysis of megakaryocytes by flow cytometry.
AB  - A flow cytofluorometric measurement of megakaryocyte ploidy has been adapted from
      Tomer's method. Briefly, bone marrow is aspirated through a medium containing
      theophyllin, prostaglandin-E1 and other antiaggregant agents. Megakaryocytes
      enriched buffy coats are recovered. Megakaryocytes are then stained for GP IIIa
      coupled with FITC and for DNA (propidium iodide). A Becton Dickinson FACScan flow
      cytometer is used for measuring the ploidy distribution of GP IIIa positive
      cells. The method we developed presents several advantages. Firstly, the time
      required is greatly decreased in comparison with other studies. Secondly, the
      washing steps are limited in number allowing a diminution of the cell loss.
      Thirdly, the method ensures a better megakaryocyte preservation. Finally,
      selection of megakaryocytes by ploidy and expression of GP IIIa can be made
      easily because of the simultaneity of the two stainings as well as by the use of
      a precise gating on the flow cytometer. Based on these results, we conclude that
      the present method provides a better means for the isolation and analysis of
      human normal megakaryocytes. This technique has been applied to the analysis of
      megakaryocyte populations from patients with abnormal platelet counts. In chronic
      myeloid leukemia patients, analysis of ploidy distribution shows a shift toward
      the low ploidy while in patients with immune thrombocytopenic purpura,
      polycythemia vera and essential thrombocythemia the ploidy distributions are
      shifted toward the high ploidy.

PMID- 10069448
TI  - Susceptibilities of plasma antioxidants and erythrocyte constituents to low
      levels of ozone.
AB  - To evaluate the susceptibilities of human blood constituents to the low levels of
      ozone used in ozonated autohemotherapy (40 microgO3/ml), we quantified plasma
      antioxidants and erythrocyte constituents after rapid mixing of human whole blood
      with ozone at 20, 40, 60, and 100 microg/ml blood. Ascorbic acid, uric acid, and
      alpha-tocopherol in plasma decreased as ozone increased, but bilirubin was
      unaffected. The content of thiobarbituric acid-reactive substances in plasma was
      increased by ozone. However, the content of thiobarbituric acid-reactive
      substances and alpha-tocopherol in the erythrocyte membrane was not significantly
      affected. No significant changes occurred in the content of methemoglobin,
      cytoskeleton proteins or erythrocyte enzymes such as Na+/K+-ATPase,
      acetylcholinesterase, catalase, glutathione peroxidase, glutathione reductase,
      and superoxide dismutase at all the ozone levels tested. A decrease in reduced
      glutathione in erythrocytes was the only significant change caused by the ozone
      level used for autohemotherapy. It may be one of the chemical events responsible
      for the beneficial effects of ozonated autohemotherapy.

PMID- 10069449
TI  - Importance of basophilia in haematopoietic disorders.
AB  - To the significance of basophilia in haematopoietic disorders, six draw attention
      to cases have been analyzed. Associated diseases included acute myelogenous
      leukaemia (AML-M2, M3, M4, and M6), refractory anaemia with excess of blasts
      (RAEB) and RAEB in transformation (RAEB-T). Two AML cases (M2, M6) were preceeded
      by myelodysplastic syndromes (MDS). All patients showed greater than 3%
      basophilia in peripheral blood and bone marrow. Basophils were identified
      successfully by metachromatic staining with toluidine blue in all cases. Three
      patients (M3, M4, RAEB) presented with lymphadenopathy, suggesting an association
      with extramedullary involvement. Neutrophil alkaline phosphatase (NAP) activity
      was significantly reduced in four patients with AML (M2, M3, M4) and RAEB-T. The
      clinical course was generally unfavourable characterized by short remission
      duration or disease progression except for the patient with RAEB. Haemorrhage was
      the main cause of death rather than infection. Cytogenetic analysis revealed
      unique abnormalities involving chromosomes 3q21, 5q31, and 17q11 where the genes
      for some haematopoietic growth factors or their receptors are located, in
      addition to t(6;9) and t(15;17).

PMID- 10069450
TI  - Mediastinal B-cell high grade non-Hodgkin's lymphoma with sclerosis: report of
      three cases.
AB  - Mediastinal large B-cell lymphomas are uncommon haematologic malignancies seen
      mostly in women. We report our recent experience with three patients, only one of
      whom survived after an autologous bone marrow transplantation.

PMID- 10069451
TI  - The value of serum soluble transferrin receptor (sTfR) determination in
      hematological malignancies.

PMID- 10069452
TI  - Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error
      positive colon cancer and azoxymethane-induced rat colonic tumors.
AB  - Evidence is accumulating which indicates that cyclooxygenase-2 (COX-2) is
      involved in the pathogenesis of colorectal cancer. We evaluated the expression of
      COX-2 in replication error-positive (RER) colon cancers, colon cancers metastatic
      to liver and azoxymethane (AOM)-induced rat colonic tumors. Immunohistochemistry
      showed that COX-2 was low to undetectable in normal human mucosa, but abundant in
      the RER adenocarcinomas we examined. COX-2 immunoreactivity in metastatic colon
      cancers was less abundant, but clearly detectable. In the colon of AOM-treated
      rats, COX-2 protein was not detectable in normal mucosa, but present in most of
      the epithelial cells comprising the tumors. The TGF-beta1 staining pattern in
      these human and rat tumors was similar to that observed for COX-2. The role of
      TGF-beta in RER adenocarcinomas is complex because of the increased mutation rate
      of TGF-beta type II receptors. Northern analysis showed abundant TGF-beta1 mRNA
      in AOM-induced tumors, but not in paired mucosa. TGF-beta1 induced the expression
      of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF
      beta1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat
      intestinal epithelial cells (RIE-1). TGF-beta1 may regulate COX-2 expression
      during the colonic adenoma to carcinoma sequence.

PMID- 10069453
TI  - Defining the substrate specificity of cdk4 kinase-cyclin D1 complex.
AB  - cdk4 kinase-cyclin D1 complex (cdk4/D1) does not phosphorylate all of the sites
      within retinoblastoma protein (Rb) equally. Comparison of five phosphorylation
      sites within the 15 kDa C domain of Rb indicates that Ser795 is the preferred
      site of phosphorylation by cdk4/D1. A series of experiments has been performed to
      determine the properties of this site that direct preferential phosphorylation.
      For cdk4/D1, the preferred amino acid at the third position C-terminal to the
      phosphorylated serine/threonine is arginine. Substitution of other amino acids,
      including a conservative change to lysine, has dramatic effects on the rates of
      phosphorylation. This information has been used to mutate less favorable sites in
      Rb, converting them to sites that are now preferentially phosphorylated by
      cdk4/D1. A conserved site at Ser842 in the related pocket protein p107 is also
      preferentially phosphorylated by cdk4/D1. Although Rb and p107 differ
      significantly in sequence, the Rb Ser795 site can replace the p107 Ser842 site
      without affecting the rate of phosphorylation. These results suggest that
      although a determinant of specificity resides in the sequences surrounding the
      phosphorylated site, the structural context of the site is also a critical
      parameter of specificity.

PMID- 10069454
TI  - Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA
      dependent protein kinase on cellular responses to DNA damage.
AB  - DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP) are
      activated by DNA strand breaks and participate in DNA repair. We investigated the
      interactive effects of inhibitors of these enzymes [wortmannin (WM), which
      inhibits DNA-PK, and 8-hydroxy-2-methylquinazolin-4-one (NU1025), a PARP
      inhibitor] on cell survival and DNA double-strand break (DSB) and single-strand
      break (SSB) rejoining in Chinese hamster ovary-K1 cells following exposure to
      ionizing radiation (IR) or temozolomide. WM (20 microM) or NU1025 (300 microM)
      potentiated the cytotoxicity of IR with dose enhancement factors at 10% survival
      (DEF10) values of 4.5 +/- 0.6 and 1.7 +/- 0.2, respectively. When used in
      combination, a DEF10 of 7.8 +/- 1.5 was obtained. WM or NU1025 potentiated the
      cytotoxicity of temozolomide, and an additive effect on the DEF10 value was
      obtained with the combined inhibitors. Using the same inhibitor concentrations,
      their single and combined effects on DSB and SSB levels following IR were
      assessed by neutral and alkaline elution. Cells exposed to IR were post-incubated
      for 30 min to allow repair to occur. WM or NU1025 increased net DSB levels
      relative to IR alone (DSB levels of 1.29 +/- 0.04 and 1.20 +/- 0.05,
      respectively, compared with 1.01 +/- 0.03 for IR alone) and the combination had
      an additive effect. WM had no effect on SSB levels, either alone or in
      combination with NU1025. SSB levels were increased to 1.27 +/- 0.05 with NU1025
      compared with IR alone, 1.02 +/- 0.04. The dose-dependent effects of the
      inhibitors on DSB levels showed that they were near maximal by 20 microM WM and
      300 microM NU1025. DSB repair kinetics were studied. Both inhibitors increased
      net DSB levels over a 3 h time period; when they were combined, net DSB levels at
      3 h were identical to DSB levels immediately post-IR. The combined use of DNA
      repair inhibitors may have therapeutic potential.

PMID- 10069455
TI  - Mismatch repair and differential sensitivity of mouse and human cells to
      methylating agents.
AB  - The long-patch mismatch repair pathway contributes to the cytotoxic effect of
      methylating agents and loss of this pathway confers tolerance to DNA methylation
      damage. Two methylation-tolerant mouse cell lines were identified and were shown
      to be defective in the MSH2 protein by in vitro mismatch repair assay. A normal
      copy of the human MSH2 gene, introduced by transfer of human chromosome 2,
      reversed the methylation tolerance. These mismatch repair defective mouse cells
      together with a fibroblast cell line derived from an MSH2-/- mouse, were all as
      resistant to N-methyl-N-nitrosourea as repair-defective human cells. Although
      long-patch mismatch repair-defective human cells were 50- to 100-fold more
      resistant to methylating agents than repair-proficient cells, loss of the same
      pathway from mouse cells conferred only a 3-fold increase. This discrepancy was
      accounted for by the intrinsic N-methyl-N-nitrosourea resistance of normal or
      transformed mouse cells compared with human cells. The >20-fold differential
      resistance between mouse and human cells could not be explained by the levels of
      either DNA methylation damage or the repair enzyme O6-methylguanine-DNA
      methyltransferase. The resistance of mouse cells to N-methyl-N-nitrosourea was
      selective and no cross-resistance to unrelated DNA damaging agents was observed.
      Pathways of apoptosis were apparently intact and functional after exposure to
      either N-methyl-N-nitrosourea or ultraviolet light. Extracts of mouse cells were
      found to perform 2-fold less long-patch mismatch repair. The reduced level of
      mismatch repair may contribute to their lack of sensitivity to DNA methylation
      damage.

PMID- 10069456
TI  - MSH3 deficiency is not sufficient for a mutator phenotype in Chinese hamster
      ovary cells.
AB  - In the yeast Saccharomyces cerevisiae, the mutS homolog protein products MSH3 and
      MSH6, each in cooperation with MSH2, play well-defined and specific roles in the
      repair of DNA mismatches and nucleotide loops. The discrete functions of the
      human homologs hMSH3 and hMSH6 are less clear and current evidence suggests that
      the substrate specificity of these proteins may be less strict. To determine the
      role of MSH3 in mammalian mismatch repair, we employed MSH3-deficient Chinese
      hamster ovary (CHO) cell lines. No significant changes in mutation rate were
      detected in the MSH3-deficient strain and there were no differences in
      sensitivity to DNA-damaging agents. Further analysis of hprt mutants did not show
      a MSH3-dependent shift in the mutant spectrum. Interestingly, thorough
      examination of four dinucleotide microsatellite regions revealed instability at
      only one locus in one of the MSH3-deficient cell lines. These data support the
      idea of a high degree of redundancy in the function of the MutS homologs MSH3 and
      MSH6, at least with respect to the control of microsatellite instability.

PMID- 10069457
TI  - Resistance to mammary tumorigenesis in Copenhagen rats is associated with the
      loss of preneoplastic lesions.
AB  - The resistance of Copenhagen (Cop) rats to mammary tumor development has recently
      been linked to three loci, but the genes have yet to be cloned and the mechanism
      of resistance is still largely unknown. In order to determine the cellular events
      associated with resistance, we prepared mammary whole mounts from Cop and
      susceptible Wistar Furth (WF) rats 0, 15, 30, 45 and 60 days after treatment with
      50 mg/kg N-methyl-N-nitrosourea (MNU). At 15 days, treated rats of both strains
      had significantly more undifferentiated structures [terminal end buds (TEBs)] and
      significantly fewer differentiated structures [alveolar buds (ABs)] than
      untreated rats. Treated Cop rats, however, had significantly more TEBs and fewer
      ABs than age-matched, treated WF rats. Histological analysis of preneoplastic
      lesions tentatively identified from the whole mounts showed that like WF rats,
      Cop rats developed early preneoplastic lesions [intraductal proliferations
      (IDPs)] by 15 days post-MNU treatment. Unlike IDPs from WF rats, however, the
      IDPs in Cop rats then decreased in number until they were absent 60 days post-MNU
      treatment. Furthermore, they failed to progress into more advanced lesions such
      as ductal carcinomas in situ (DCIS). Finally, we found G-->A activating mutations
      in codon 12 of the Ha-ras gene in 60% of IDPs from Cop rats and 75% of IDPs from
      WF rats. Our results show that resistance in Cop rats is not due to a target cell
      population for the carcinogen that is smaller than in susceptible rats or to the
      failure of the carcinogen to inhibit mammary gland differentiation. Furthermore,
      we have shown that Cop rats develop preneoplastic IDPs that harbor Ha-ras
      mutations but, unlike IDPs in susceptible strains, they fail to progress and
      ultimately disappear.

PMID- 10069458
TI  - Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu
      oncogene transformed human mammary epithelial cells by N-(4
      hydroxyphenyl)retinamide.
AB  - Epithelial cells from non-cancerous mammary tissue in response to exposure to
      chemical carcinogens or transfection with oncogenes exhibit hyperproliferation
      and hyperplasia prior to the development of cancer. Aberrant proliferation may,
      therefore, represent a modifiable early occurring preneoplastic event that is
      susceptible to chemoprevention of carcinogenesis. The synthetic retinoid N-(4
      hydroxyphenyl)retinamide (HPR), has exhibited preventive efficacy in several in
      vitro and in vivo breast cancer models, and represents a promising
      chemopreventive compound for clinical trials. Clinically relevant biochemical and
      cellular mechanisms responsible for the chemopreventive effects of HPR, however,
      are not fully understood. Experiments were performed on preneoplastic human
      mammary epithelial 184-B5/HER cells derived from reduction mammoplasty and
      initiated for tumorigenic transformation by overexpression of HER-2/neu oncogene,
      to examine whether HPR inhibits aberrant proliferation of these cells and to
      identify the possible mechanism(s) responsible for the inhibitory effects of HPR.
      Continuous 7-day treatment with HPR produced a dose-dependent, reversible growth
      inhibition. Long-term (21 day) treatment of 184-B5/HER cells with HPR inhibited
      anchorage-dependent colony formation by approximately 80% (P < 0.01) relative to
      that observed in the solvent control. A 24 h treatment with cytostatic 400 nM HPR
      produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01)
      in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P =
      0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of
      the antioxidant N-acetyl-L-cysteine. Treatment with HPR resulted in a 30%
      reduction of cellular immunoreactivity to tyrosine kinase, whereas
      immunoreactivity to p185HER remained essentially unaltered. HPR exposure resulted
      in time-dependent increase in cellular metabolism of the retinoid as evidenced by
      increased formation of the inert metabolite N-(4-methoxyphenyl)-retinamide (MPR)
      and progressive increase in apoptosis. Thus, HPR-induced inhibition of aberrant
      proliferation may be caused, in part, by its ability to inhibit HER-2/neu
      mediated proliferative signal transduction, retard cell cycle progression and
      upregulate cellular apoptosis.

PMID- 10069459
TI  - Resveratrol suppresses cell transformation and induces apoptosis through a p53
      dependent pathway.
AB  - Resveratrol, a plant constituent enriched in the skin of grapes, is one of the
      most promising agents for the prevention of cancer. However, the mechanism of the
      anti-carcinogenic activity of resveratrol is not well understood. Here we offer a
      possible explanation of its anti-cancer effect. Resveratrol suppresses tumor
      promoter-induced cell transformation and markedly induces apoptosis,
      transactivation of p53 activity and expression of p53 protein in the same cell
      line and at the same dosage. Also, resveratrol-induced apoptosis occurs only in
      cells expressing wild-type p53 (p53+/+), but not in p53-deficient (p53-/-) cells,
      while there is no difference in apoptosis induction between normal lymphoblasts
      and sphingomyelinase-deficient cell lines. These results demonstrate for the
      first time that resveratrol induces apoptosis through activation of p53 activity,
      suggesting that its anti-tumor activity may occur through the induction of
      apoptosis.

PMID- 10069460
TI  - Characterization of cytochrome P450 expression in human oesophageal mucosa.
AB  - The expression of cytochrome (CYP) P450 enzymes in human oesophageal mucosa was
      investigated in a total of 25 histologically non-neoplastic surgical tissue
      specimens by using specific antibodies in immunoblots and by RT-PCR mRNA
      analysis. The presence of CYP1A, 2E1, 3A and 4A enzymes was demonstrated by both
      techniques; CYP2A reactive protein was also detected by immunoblot. The presence
      of CYP4B1 mRNA was established but no specific antibody was available for
      detection of the corresponding protein by immunoblot. CYP2B6/7 mRNA was not
      detected in any sample. The mRNA transcripts for CYP1A1, 2E1, 4A11 and 4B1 were
      consistently detected in the majority of samples (>84%), whereas CYP1A2 mRNA was
      only detected in 11 of 19 specimens examined. An RT-PCR method to differentiate
      CYP3A4 and 3A5 mRNA was developed. This demonstrated CYP3A5 mRNA expression in
      all samples tested, whereas CYP3A4 mRNA was not detectable, suggesting that
      CYP3A5 is the major CYP3A protein in human oesophagus. There were significant
      interindividual variations in the amount of proteins, ranging from 8-fold for
      CYP4A to 43-fold for CYP2E1. For each patient, data on exposure to risk factors
      for oesophageal cancer were available, including tobacco smoke, alcohol, gastro
      oesophageal reflux and hot beverage consumption. None of these risk factors or
      other patient characteristics (age, sex, tumour location and tumour stage) were
      correlated with the protein level of the individual CYP enzymes as determined by
      quantitation of immunoblot staining. However, the small series of samples
      precludes any strong conclusion concerning the lack of such correlations. There
      were no differences between squamous cell carcinomas and adenocarcinomas in
      either the qualitative or quantitative expression of the CYP enzymes. These data
      demonstrate that a range of CYP enzymes are expressed in human oesophageal mucosa
      and indicate that this tissue has the capacity to activate chemical carcinogens
      to reactive DNA binding metabolites.

PMID- 10069461
TI  - Fish oil constituent docosahexa-enoic acid selectively inhibits growth of human
      papillomavirus immortalized keratinocytes.
AB  - The omega-3-fatty acids inhibit proliferation of breast cancer cells whereas
      omega-6-fatty acids stimulate growth. In this study, we examined effects of these
      fatty acids on human pre-cancerous cells. Cervical keratinocytes, immortalized
      with the oncogenic human papillomavirus (HPV) type 16, were treated with linoleic
      acid, an omega-6-fatty acid, and the omega-3-fatty acids, eicosapentaenoic and
      docosahexaenoic acids. Using both cell counts and bromodeoxyuridine
      incorporation, docosahexaenoic acid inhibited growth of these cells to a greater
      extent than eicosapenta-enoic acid. Linoleic acid had no effect. The effect of
      docosahexaenoic acid was dose dependent and caused growth arrest. Docosahexaenoic
      acid inhibited growth of HPV16 immortalized foreskin keratinocytes and laryngeal
      keratinocytes grown from explants of benign tumors caused by papillomavirus, but
      had no effect on normal foreskin and laryngeal keratinocytes. Docosahexaenoic
      acid inhibited growth in the presence of estradiol, a growth stimulator for these
      cells. Indomethacin, a cyclooxygenase inhibitor like docosahexaenoic acid, had
      only minimal effect on growth. Alpha-tocopherol, a peroxidation inhibitor,
      abrogated effects of docosahexaenoic acid implying that inhibitory effects were
      via lipid peroxidation.

PMID- 10069462
TI  - Effect of retinoids on AOM-induced colon cancer in rats: modulation of cell
      proliferation, apoptosis and aberrant crypt foci.
AB  - We have previously reported that the retinoids, 4-(hydroxyphenyl)retinamide (4
      HPR) and 9-cis-retinoic acid (RA) prevented azoxymethane (AOM)-induced colon
      tumors and along with 2-(carboxyphenyl)retinamide (2-CPR) prevented aberrant
      crypt foci (ACF). In this study, we evaluated the effect of 2-CPR on AOM-induced
      colon tumors and the effect of the three retinoids on apoptosis and cell
      proliferation. Male F344 rats were administrated 15 mg/kg AOM at weeks 7 and 8 of
      age. 2-CPR (315 mg/kg) was administered in the diet starting either 1 week before
      or at week 12 after the first dose of AOM. The rats continued to receive the 2
      CPR until killed at week 46. Unlike the demonstrated prevention of colon cancer
      by the other two retinoids, both dosing schedules of 2-CPR resulted in an
      approximate doubling of the yield of colon tumors. In adenomas, 2-CPR, 4-HPR and
      9-cis-RA were equally effective in reducing mitotic activity, while only 4-HPR
      and 9-cis-RA but not 2-CPR enhanced apoptosis. When administered for only the 6
      days prior to killing 4-HPR but not 2-CPR decreased the Mitotic Index and
      increased the Apoptotic Index in adenomas. In non-involved crypts, chronic
      exposure to 4-HPR and 9-cis-RA in contrast to 2-CPR reduced the Mitotic Index and
      enhanced the Apoptotic Index. In concurrence with our previous study, both 2-CPR
      and 4-HPR were very potent in preventing ACF when administered in the diet
      starting 1 week before the first dose of AOM and continuing for the 5 weeks of
      the study. Hence, unlike the other two retinoids, 2-CPR, although very potent in
      preventing ACF, enhanced rather than prevented AOM-induced colon cancer.
      Furthermore, our results suggest that the effect of 2-CPR on tumor yield is
      different from 4-HPR and 9-cis-RA because, unlike them, it does not enhance
      apoptosis.

PMID- 10069463
TI  - The major, N2-dG adduct of (+)-anti-B[a]PDE induces G-->A mutations in a 5'-AGA
      3' sequence context.
AB  - Previously, in a random mutagenesis study, the (+)-anti diol epoxide of
      benzo[a]pyrene [(+)-anti-B[a]PDE] was shown to induce a complex mutational
      spectrum in the supF gene of an Escherichia coli plasmid, which included
      insertions, deletions and base substitution mutations, notably a significant
      fraction of GC-->TA, GC-->AT and GC-->CG mutations. At some sites, a single type
      of mutation dominated and to understand individual mutagenic pathways these sites
      were chosen for study by site-specific means to determine whether the major
      adduct, [+ta]-B[a]P-N2-dG, was responsible. [+ta]-B[a]P-N2-dG was shown to induce
      approximately 95% G-->T mutations in a 5'-TGC-3' sequence context and
      approximately 80% G-->A mutations in a 5'-CGT-3' sequence context. (+)-anti
      B[a]PDE induced principally GC-->CG mutations in the G133 sequence context (5'
      AGA-3') in studies using both SOS-uninduced or SOS-induced E. coli. Herein, [+ta]
      B[a]P-N2-dG is shown to induce principally G-->A mutations (>90%) either without
      or with SOS induction in a closely related 5'-AGA-3' sequence context (identical
      over 7 bp). This is the first time that there has been a discrepancy between the
      mutagenic specificity of (+)-anti-B[a]PDE versus [+ta]-B[a]P-N2-dG. Eight
      explanations for this discordance are considered. Four are ruled out; e.g. the
      second most prevalent adduct [+ca]-B[a]P-N2-dG also induces a preponderance of G-
      >A mutations (>90%), so it also is not responsible for (+)-anti-B[a]PDE-induced
      G133-->C mutations. The four explanations not ruled out are discussed and include
      that another minor adduct might be responsible and that the 5'-AGA-3' sequence
      context differed slightly in the studies with [+ta]-B[a]P-N2-dG versus (+)-anti
      B[a]PDE. In spite of the discordance, [+ta]-B[a]P-N2-dG induces G-->A mutations
      in the context studied herein and this result has proven useful in generating a
      hypothesis for what conformations of [+ta]-B[a]P-N2-dG are responsible for G-->T
      versus G-->A mutations.

PMID- 10069464
TI  - Hprt mutant frequency and molecular analysis of Hprt mutations in Fischer 344
      rats treated with thiotepa.
AB  - Thiotepa is a bifunctional alkylating anticancer drug that is a rodent carcinogen
      and a suspected human carcinogen. In order to determine the sensitivity of mutant
      induction in the Hprt lymphocyte assay for detecting tumorigenic doses of
      thiotepa, Fischer 344 rats were treated for 4 weeks with thiotepa using a
      procedure adapted from a carcinogenesis protocol. At various times after
      beginning the treatment regimen, rats were killed and the lymphocyte Hprt assay
      was performed on splenic lymphocytes isolated from the animals. The 6-thioguanine
      resistant T lymphocyte mutant frequency increased with time during the period of
      thiotepa exposure and declined slightly thereafter. Significant dose-dependent
      increases in mutant frequency were found using concentrations of thiotepa that
      eventually result in lymphoproliferative tumors. Hprt mRNA from mutant
      lymphocytes was reverse transcribed to cDNA, amplified by PCR and examined for
      mutations by DNA sequencing. This analysis indicated that the major type of point
      mutation was G:C-->T:A transversion and that 33% of the mutants contained simple
      or complex frameshifts. Also, a multiplex PCR performed on DNA from mutant clones
      that were expanded in vitro indicated that 34% of the clones had deletions in the
      Hprt gene. These results indicate that the induction of lymphocyte Hprt mutants
      is a sensitive biomarker for the carcinogenicity of thiotepa and that the types
      of mutations found in the lymphocyte Hprt gene reflect the kinds of DNA damage
      produced by thiotepa.

PMID- 10069465
TI  - Reduced lung tumorigenesis in human methylguanine DNA--methyltransferase
      transgenic mice achieved by expression of transgene within the target cell.
AB  - Human methylguanine-DNA methyltransferase (MGMT) transgenic mice expressing high
      levels of O6-alkylguanine-DNA alkyltransferase (AGT) in lung were crossbred to
      A/J mice that are susceptible to pulmonary adenoma to study the impact of O6
      methylguanine (O6mG)-DNA adduct repair on NNK-induced lung tumorigenesis.
      Expression of the chimeric human MGMT transgene in lung was identified by
      northern and western blot analysis, immunohistochemistry assay and enzymatic
      assay. AGT activity was 17.6 +/- 3.2 versus 1.2 +/- 0.4 fmol/microg DNA in lung
      of MGMT transgenic mice compared with non-transgenic mice. Immunohistochemical
      staining with anti-human AGT antibody showed that human AGT was expressed
      throughout the lung. However, some epithelial cells of bronchi and alveoli did
      not stain for human AGT, suggesting that the human MGMT transgene expression was
      heterogeneous. After 100 mg/kg NNK i.p. injection in MGMT transgenic mice, lung
      AGT activity remained much higher and levels of lung O6mG-DNA adducts in MGMT
      transgenic mice were lower than those of non-transgenic mice. In the
      tumorigenesis study, mice received 100 mg/kg NNK at 6 weeks of age and were
      killed 44 weeks later. Ten of 17 MGMT transgenic mice compared with 16 of 17 non
      transgenic mice had lung tumors, P < 0.05. MGMT transgenic mice had lower
      multiplicity and smaller sized lung tumors than non-transgenic mice. Moreover, a
      reduction in the frequency of K-ras mutations in lung tumors was found in MGMT
      transgenic mice (6.7 versus 50% in non-transgenic mice). These results indicate
      that high levels of AGT expressed in mouse lung reduce lung tissue susceptibility
      to NNK-induced tumorigenesis due to increased repair capacity for O6mG,
      subsequently, decreased mutational activation of K-ras oncogene. Heterogeneity in
      the level of AGT expressed in different lung cell populations or other forms of
      carcinogenic DNA damage caused by NNK may explain the residual incidence of lung
      tumors in MGMT transgenic mice.

PMID- 10069466
TI  - In vitro reactions of butadiene monoxide with single- and double-stranded DNA:
      characterization and quantitation of several purine and pyrimidine adducts.
AB  - We have previously shown that butadiene monoxide (BM), the primary metabolite of
      1,3-butadiene, reacted with nucleosides to form alkylation products that
      exhibited different rates of formation and different stabilities under in vitro
      physiological conditions. In the present study, BM was reacted with single
      stranded (ss) and double-stranded (ds) calf thymus DNA and the alkylation
      products were characterized after enzymatic hydrolysis of the DNA. The primary
      products were regioisomeric N-7-guanine adducts. N-3-(2-hydroxy-3-buten-1
      yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine, which were depurinated from
      the DNA more rapidly than the N-7-guanine adducts, were also formed. In addition,
      N6-(2-hydroxy-3-buten-1-yl)deoxyadenosine and N6-(1-hydroxy-3-buten-2
      yl)deoxyadenosine were detected and evidence was obtained that these adducts were
      formed by Dimroth rearrangement of the corresponding N-1-deoxyadenosine adducts,
      not while in the DNA, but following the release of the N-1-alkylated nucleosides
      by enzymatic hydrolysis. N-3-(2-hydroxy-3-buten-1-yl)deoxyuridine adducts, which
      were apparently formed subsequent to deamination reactions of the corresponding
      deoxycytidine adducts, were also detected and were stable in the DNA. Adduct
      formation was linearly dependent upon BM concentration (10-1000 mM), with adduct
      ratios being similar at the various BM concentrations. At a high BM concentration
      (750 mM), the adducts were formed in a linear fashion for up to 8 h in both ssDNA
      and dsDNA. However, the rates of formation of the N-3-deoxyuridine and N6
      deoxyadenosine adducts increased 10- to 20-fold in ssDNA versus dsDNA, whereas
      the N-7-guanine adducts increased only slightly, presumably due to differences in
      hydrogen bonding in ssDNA versus dsDNA. These results may contribute to a better
      understanding of the molecular mechanisms of mutagenesis and carcinogenesis of
      both BM and its parent compound, 1,3-butadiene.

PMID- 10069467
TI  - Idoxifene derivatives are less reactive to DNA than tamoxifen derivatives, both
      chemically and in human and rat liver cells.
AB  - The drug tamoxifen shows evidence of genotoxicity, and induces liver tumours in
      rats. Covalent DNA adducts have been detected in the liver of rats treated with
      tamoxifen, and these arise through metabolism at the alpha-position to give an
      ester which reacts with DNA. (E)-1-(4-iodophenyl)-2-phenyl-1-[4-(2
      pyrrolidinoethoxy)phenyl]-but-1-en e (idoxifene) is an analogue of tamoxifen in
      which formation of DNA adducts is greatly reduced; we could not detect any
      adducts in the DNA of cultured rat hepatocytes treated with 10 microM idoxifene,
      after analysis by the 32P-post-labelling method. The metabolite (Z)-4-(4
      iodophenyl)-4-[4-(2-pyrrolidinoethoxy)phenyl]-3-phenyl-3-but en-2-ol (alpha
      hydroxyidoxifene) gave adducts in rat hepatocytes, but far fewer than the
      corresponding tamoxifen metabolite. In human hepatocytes, neither idoxifene nor
      tamoxifen induced detectable levels of DNA adducts. We prepared the alpha-acetoxy
      ester of idoxifene as a model for the ultimate reactive metabolite formed in rat
      liver. It was less reactive than alpha-acetoxytamoxifen, as might be expected on
      mechanistic grounds. It reacted with DNA in the same way, to give adducts which
      were probably N2-alkyldeoxyguanosines, but to a lower extent. All these results
      indicate that idoxifene is much less genotoxic than tamoxifen, and should
      therefore be a safer drug.

PMID- 10069468
TI  - Administration of an unconjugated bile acid increases duodenal tumors in a murine
      model of familial adenomatous polyposis.
AB  - Intestinal carcinogenesis involves the successive accumulation of multiple
      genetic defects until cellular transformation to an invasive phenotype occurs.
      This process is modulated by many epigenetic factors. Unconjugated bile acids are
      tumor promoters whose presence in intestinal tissues is regulated by dietary
      factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in
      an animal model of familial adenomatous polyposis. Mice susceptible to intestinal
      tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10
      week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were
      examined to determine tumor number, enterocyte proliferation, apoptosis and beta
      catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also
      assessed. Administration of chenodeoxycholate in the diet increased duodenal
      tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied
      by increased beta-catenin expression in duodenal cells, as well as increased PGE2
      in duodenal tissue. These data suggest that unconjugated bile acids contribute to
      periampullary tumor formation in the setting of an Apc mutation.

PMID- 10069469
TI  - Identification of the major tamoxifen-DNA adducts in rat liver by mass
      spectroscopy.
AB  - We present here the first mass spectroscopic (MS) identification of the main
      tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by
      high-performance liquid chromatography (HPLC) and identified by MS, MS-MS and
      ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen-deoxyguanosine
      adduct in which the alpha-position of the metabolite N-desmethyltamoxifen is
      linked covalently to the amino group of deoxyguanosine. Adduct 2 was confirmed to
      be the trans isomer of alpha-(N2-deoxyguanosinyl)tamoxifen, as previously
      suggested by co-chromatography.

PMID- 10069470
TI  - Expression cloning for arsenite-resistance resulted in isolation of tumor
      suppressor fau cDNA: possible involvement of the ubiquitin system in arsenic
      carcinogenesis.
AB  - Arsenic is a human carcinogen whose mechanism of action is unknown. Previously,
      this laboratory demonstrated that arsenite acts as a comutagen by interfering
      with DNA repair, although a specific DNA repair enzyme sensitive to arsenite has
      not been identified. A number of stable arsenite-sensitive and arsenite-resistant
      sublines of Chinese hamster V79 cells have now been isolated. In order to gain
      understanding of possible targets for arsenite's action, one arsenite-resistant
      subline, As/R28A, was chosen as a donor for a cDNA expression library. The
      library from arsenite-induced As/R28A cells was transfected into arsenite
      sensitive As/S5 cells, and transfectants were selected for arsenite-resistance.
      Two cDNAs, asr1 and asr2, which confer arsenite resistance to arsenite
      hypersensitive As/S5 cells as well as to wild-type cells, were isolated. asr1
      shows almost complete homology with the rat fau gene, a tumor suppressor gene
      which contains a ubiquitin-like region fused to S30 ribosomal protein. Arsenite
      was previously shown to inhibit ubiquitin-dependent proteolysis. These results
      suggest that the tumor suppressor fau gene product or some other aspect of the
      ubiquitin system may be a target for arsenic toxicity and that disruption of the
      ubiquitin system may contribute to the genotoxicity and carcinogenicity of
      arsenite.

PMID- 10069471
TI  - Induction of adenocarcinoma from hamster pancreatic islet cells treated with N
      nitrosobis(2-oxopropyl)amine in vitro.
AB  - Our previous studies in the hamster pancreatic cancer model have indicated that
      pancreatic ductal adenocarcinomas derive not only from ductal/ductular cells but
      also from islets. To verify the presence of carcinogen-responsive cells within
      islets, we tested the effect of the pancreatic carcinogen N-nitrosobis(2
      oxopropyl)amine (BOP) on recently established continuous hamster pancreatic islet
      culture. Isolated pure pancreatic islets of hamsters were treated in vitro with
      BOP at a concentration of 0.25 mM three times a week for 19 weeks. Each treatment
      week was designed as a stage. The growth of these cells, designated KL5B, was
      compared with untreated cultured islets, designated KL5N. As in our previous
      study, between 14 and 21 days of culture, exocrine and intermediary cells
      developed within both KL5N and KL5B islets, which were then replaced by
      undifferentiated cells. No differences were found in the growth patterns of KL5N
      and KL5B until stage 4, when KL5B cells showed accelerated cell growth and cell
      pleomorphism, which increased gradually at later stages of treatment. Anchorage
      independent and in vivo growth did not appear until stage 19. Mutation of c-Ki
      ras at codon 12 (GGT-->GAT) was detected in KL5B cells but not in KL5N cells. In
      vivo KL5B cells formed anaplastic invasive cancer with areas of glandular
      formation, overexpressed TGF-alpha and EGFR, expressed cytokeratin, vimentin,
      laminin and alpha-1 antitrypsin and reacted strongly with L-phytohemagglutinin
      and tomato lectin. Some cells within islets are responsive to the carcinogenic
      effects of BOP. Whether these cells represent islet cell precursors (stem cells)
      or malignant transdifferentiated islet cells remains to be seen.

PMID- 10069472
TI  - Possible carcinogenic effects of X-rays in a transgenerational study with CBA
      mice.
AB  - A lifetime experiment using 4279 CBA/J mice was carried out to investigate
      whether the pre-conceptual exposure of sperm cells to X-ray radiation or urethane
      would result in an increased cancer risk in the untreated progeny, and/or
      increased susceptibility to cancer following exposure to a promoting agent. The
      study consisted of four main groups, namely a control group (saline), a urethane
      group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9
      weeks after treatment, the males of these four parental groups were mated with
      untreated virgin females. The offspring of each parental group was divided into
      two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter,
      the other saline, at the age of 6 weeks. All animals were evaluated for the
      occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations
      were investigated in frozen lung tumour samples. The female offspring of male
      parents exposed to X-rays 1 week before their mating showed a trend towards a
      higher tumour incidence of the haematopoietic system than the F1 controls. In
      addition, a higher percentage of bronchioloalveolar adenocarcinomas in male
      offspring born to irradiated paternals mated 1 week after X-ray treatment points
      to a plausible increased sensitivity of post-meiotic germ cell stages towards
      transgenerational carcinogenic effects. On the other hand, no increased tumour
      incidence and malignancy were observed in the offspring born to irradiated
      paternals mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment
      1, 3 and 9 weeks prior to conception did not result in significantly altered
      incidence or malignancy of tumours of the lung, liver and haematopoietic tissue
      in the offspring. K-ras mutations increased during tumour progression from
      bronchioloalveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more
      frequent in lung tumours of urethane-promoted progeny from irradiated parents
      than from control parents. P53 mutations were absent from these lung alterations.

PMID- 10069473
TI  - Influence of glutathione levels and heat-shock on the steady-state levels of
      oxidative DNA base modifications in mammalian cells.
AB  - The effects of thiols, ascorbic acid and thermal stress on the basal (steady
      state) levels of oxidative DNA base modifications were studied. In various types
      of untreated cultured mammalian cells, the levels of total glutathione were found
      to be inversely correlated with the levels of DNA base modifications sensitive to
      the repair endonuclease Fpg protein, which include 8-hydroxyguanine (8-oxoG). A
      depletion of glutathione by treatment with buthionine sulphoximine increased the
      steady-state level in AS52 Chinese hamster cells by approximately 50%. However,
      additional thiols in the culture medium did not reduce the level of Fpg-sensitive
      base modifications: 0-10 mM N-acetylcysteine had no effect, whereas cysteine
      ethylester even increased the oxidative DNA damage at concentrations >0.1 mM.
      Similarly, ascorbic acid (0-20 mM) failed to reduce the steady-state levels. When
      AS52 cells were grown at elevated temperature (41 degrees C), the steady-state
      level of the oxidative DNA modifications increased by 40%, in spite of a
      concomitant 1.6-fold increase of the cellular level of total glutathione.
      Depletion of glutathione at 41 degrees C nearly doubled the already elevated
      level of oxidative damage. A constitutive expression of the heat-shock protein
      Hsp27 in L929 mouse fibrosarcoma cells at 37 degrees C increased the glutathione
      level by 60%, but had little effect on the level of oxidative DNA damage.

PMID- 10069474
TI  - Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the
      human endometrium.
AB  - Tamoxifen is associated with an increased incidence of endometrial cancer in
      women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts
      in this tissue. A previous study exploring DNA adducts in human endometria,
      utilizing thin layer chromatography 32P-postlabelling, found no evidence for
      adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P.,
      Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479].
      However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K.,
      Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377]
      suggested that very low levels could be detected. We have sought to investigate
      this question further by reproducing the HPLC methodology at two centres, and
      analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for
      between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used
      as a positive control. We found no convincing evidence for tamoxifen-derived DNA
      adducts in human endometrium. HPLC elution profiles of post-labelled DNA from
      tamoxifen-treated women were indistinguishable from those obtained with DNA from
      14 untreated women and from six women taking toremifene, an analogue of
      tamoxifen.

PMID- 10069475
TI  - 5-Aza-2'-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3
      pyridyl)-1-butanone-induced primary mouse lung tumor model.
AB  - Carcinogenesis is a multistep process in which many alterations in both genetic
      and epigenetic controls lead to a growth advantage for neoplastic cells.
      Hypermethylation has been established as the basis of genomic imprinting, but
      recent studies have also shown that alterations in genomic methylation patterns
      may contribute to tumorigenesis. The chemical 5-aza-2'-deoxycytidine (5-aza-dC)
      has been used both in vitro and in vivo to inhibit DNA methylation. In this
      study, we investigated the chemopreventive efficacy of 5-aza-dC in a well
      established primary mouse lung tumor model. Five-week-old male (C3H/HeJ x A/J) F1
      hybrid mice were treated for 24 consecutive weeks with 5-aza-dC, three times per
      week i.p. Lung tumors were induced with two consecutive weekly doses of 4-(methyl
      nitrosamino)-1-(3-pyridyl)-1-butanone starting 1 week after initial treatment
      with 5-aza-dC. We demonstrated that 5-aza-dC exhibits a chemopreventive effect in
      this primary mouse lung tumor model which, like human lung adenocarcinomas,
      harbors an activating K-ras mutation. Treatment with 5-aza-dC resulted in a 23%
      reduction in tumor incidence, as well as a 42% reduction in tumor multiplicity.
      This work supports further investigation of methylation inhibitors likes 5-aza-dC
      for early intervention, prevention and treatment of lung cancer.

PMID- 10069476
TI  - Pseudoenzymatic reduction of N-hydroxy-2-acetylaminofluorene to 2
      acetylaminofluorene mediated by cytochrome P450.
AB  - N-hydroxy-2-acetylaminofluorene (N-OH-AAF) was reduced to 2-acetylaminofluorene
      by rat liver microsomes in the presence of both NAD(P)H and FAD under anaerobic
      conditions. The microsomal reduction proceeds as if it were an enzymatic
      reaction. However, when the microsomes were boiled, the activity was not
      abolished, but was enhanced. The activity was also observed with cytochrome P450
      2B1 alone, without NADPH-cytochrome P450 reductase, in the presence of these
      cofactors. Hematin also exhibited a significant reducing activity in the presence
      of both a reduced pyridine nucleotide and FAD. The activities of microsomes,
      cytochrome P450 2B1 and hematin were also observed upon the addition of
      photochemically reduced FAD instead of both NAD(P)H and FAD. The microsomal
      reduction of N-OH-AAF appears to be a non-enzymatic reaction by the reduced
      flavin, catalyzed by the heme group of cytochrome P450.

PMID- 10069477
TI  - Heterocyclic amines in process flavours, process flavour ingredients, bouillon
      concentrates and a pan residue.
AB  - Seven process flavours, five process flavour ingredients, four bouillon
      concentrates and a pan residue were analysed for mutagenic/carcinogenic
      heterocyclic amines. To improve chromatographic efficiency for samples with
      complex matrixes (process flavours, pan residues, etc.), a new additional
      purification method was designed. The following polar heterocyclic amines were
      detected: 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in one sample (3.4 ng/g),
      2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx) in two samples (0.7-2.0 ng/g), 2
      amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in four samples (1.0-13.8
      ng/g), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in three
      samples (1.3-2.9 ng/g), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8
      DiMeIQx) in one sample (0.3 ng/g), and traces of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in two samples. 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline (MeIQ) was not identified in any of the samples.
      The following non-polar heterocyclic amines were detected: 2-amino-9H-pyrido[2,3
      b]indole (AalphaC) in one sample (0.4 ng/g), 2-amino-3-methyl-9H-pyrido[2,3
      b]indole (MeAalphaC) in one sample (20.3 ng/g), 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) in two samples (1.4-1.7 ng/g), and traces of 3
      amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in two samples. Of the co
      mutagenic heterocyclic amines, 1-methyl-9H-pyrido[3,4-b]indole (harman) was
      identified in 15 of 17 samples (3.3-755 ng/g), and 9H-pyrido[3,4-b]indole
      (norharman) in 16 of 17 samples (1.2-176 ng/g). The polar heterocyclic amines
      were detected only in the samples of animal and mixed animal plus vegetable
      origin, while the non-polar heterocyclic amines were identified in samples of
      animal, mixed animal plus vegetable and pure vegetable origin.

PMID- 10069478
TI  - Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity
      using a combination of in vivo and in vitro assays.
AB  - Phytosterols are natural constituents of the human diet, and as part of an
      extensive programme of safety evaluation studies investigating their use as a
      novel food ingredient, the possible oestrogenic effects of phytosterols have been
      investigated using a combination of in vitro and in vivo assays. Competitive
      binding with the immature rat uterine oestrogen receptor (ER) has been used to
      measure the ability of phytosterols to bind to ERs while the transcriptional
      activation of oestrogen-responsive genes has been examined in an oestrogen
      inducible yeast screen. Phytosterols did not display any activity in these in
      vitro assays. Uterotrophic assays have been conducted to investigate the
      potential for phytosterols to elicit an oestrogenic response when administered
      orally to immature female rats (n = 10) at doses of 0, 5, 50 or 500 mg/kg/day for
      3 consecutive days. Phytosterols (a well characterized mixture of beta
      sitosterol, campesterol and stigmasterol) and phytosterol esters (the previous
      phytosterol mixture esterified with fatty acids from sunflower oil) did not
      exhibit oestrogenic activity in the immature female rat using uterine wet weight
      as the endpoint. Beta-oestradiol (0.4 mg/kg/day) consistently produced a
      significant increase in uterus weights. Coumestrol (a known phytoestrogen) was
      also tested as a weak positive control and produced a dose response at doses of
      20, 40 and 80 mg/kg/day in the uterotrophic assay. In conclusion, we have shown
      that phytosterols do not bind to the ER and do not stimulate transcriptional
      activity of the human ER in a recombinant yeast strain. In addition, there was no
      indication of oestrogenicity from the uterotrophic assay when the material was
      administered by oral gavage to immature female rats.

PMID- 10069479
TI  - Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3
      month rat oral safety study with an in utero phase.
AB  - Owing to the presence of the polyunsaturated fatty acids (PUFA) docosahexaenoic
      acid (DHA) and arachidonic acid (ARA) in human milk and their important
      biological function, several authorities recommend that they be added to infant
      formulas. This study assessed the safety of an algal oil rich in DHA and a fungal
      oil rich in ARA, blended to provide a DHA to ARA ratio similar to human milk. The
      oil blend was incorporated into diets and fed to rats such that they received 3,
      11 and 22 times the anticipated infant exposure to DHA and ARA. Low-fat and high
      fat control groups received canola oil. Rats received experimental diets over a
      premating interval and throughout mating, gestation and lactation. Pups born
      during this period (F1) consumed treatment diets from weaning for 3 months.
      Physical observations, ophthalmoscopic examinations, body weight, food intake,
      clinical chemistry, neurobehavioural evaluations and postmortem histopathology of
      selected tissues were performed. No statistically significant, dose-dependent
      adverse effects were seen in reproductive performance or fertility, nor in the
      neonates from birth to weaning. Mid- and high-dose treated F1 animals exhibited
      increased white cell count, neutrophil count and blood urea nitrogen; increased
      liver and spleen weights (absolute and relative to body weight) also were
      observed. There were no corresponding microscopic findings. The clinical
      pathology and organ weight differences at these treatment levels represent
      physiological or metabolic responses to the test substance rather than adverse
      responses. These single-cell oils produced no adverse effects in rats when
      administered in utero and for 90 days at dietary levels resulting in exposures up
      to 22 or 66 times higher than those expected in infant formulas when extrapolated
      on the basis of diet composition (g/100 Cal) or intake (g/kg body weight),
      respectively.

PMID- 10069480
TI  - Effect of dietary phytate on magnesium bioavailability and liver oxidant status
      in growing rats.
AB  - Male albino rats (initial average weight 60 g) were fed semi-synthetic diets
      based on casein, corn starch and sunflower oil over 21 days. All diets were
      supplemented with 300 mg magnesium from MgSO4x7H2O and 0,7.5 and 15 g phytic acid
      (PA) from sodium phytate per kg. The addition of PA to the diets resulted in a
      dose-dependent decrease of apparent Mg absorption and Mg concentration in the
      plasma and femur. Impaired Mg bioavailability due to 15 g PA/kg diet was
      accompanied by an increase of hepatic thiobarbituric acid reactive substances and
      protein carbonyls as well as by a moderate decline in liver reduced glutathione
      (GSH) levels. The liver homogenates of rats receiving the diets with 7.5 and 15 g
      PA/kg, respectively, were much more susceptible to iron-induced lipid
      peroxidation than those of the controls. Hepatic antioxidative enzymes
      [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx),
      glucose-6-phosphate dehydrogenase (G6PDH)], alpha-tocopherol concentration and
      phenyl-N-tert-butylnitrone (PBN) adducts using electron spin resonance
      spectroscopy remained unchanged by the different dietary treatments. Under the
      conditions of a marginal dietary Mg supply, phytate had pro-oxidative rather than
      antioxidative effects in the case of liver metabolism.

PMID- 10069481
TI  - Apparent digestibility and glycaemic responses to an experimental induced
      viscosity dietary fibre incorporated into an enteral formula fed to dogs
      cannulated in the ileum.
AB  - The purpose of this study was to evaluate the apparent digestibility and
      postprandial glycaemic responses of ileal-cannulated dogs when fed an
      experimental induced viscosity dietary fibre (IVF) incorporated into a liquid
      enteral formula. Dietary treatments were: (1) control; (2) Glucerna; (3) Glytrol;
      (4) IVF; and (5) Jevity. Diets varied in concentrations of crude protein (CP),
      fat, starch and total dietary fibre (TDF). Dry matter and starch intakes by dogs
      fed the Glucerna and Glytrol treatments were lower (P<0.05) than for those
      consuming the other diets. However, daily intakes of CP and fat followed a
      reverse trend. Digestibility of nutrients at the ileum was high (>80%) for all
      dietary treatments. Mineral absorption proximal to the ileum and from the total
      tract was not significantly different among treatments. Mean incremental area
      under the serum glucose response curves for dogs fed Glytrol, Glucerna, and IVF
      treatments were lower (P<0.05) than the control treatment. Induced viscosity
      fibre appears to have no negative effects on nutrient digestion throughout the
      gastrointestinal tract. Its ability to moderate serum glucose concentrations
      would make it a potentially good choice for a diabetic liquid formula.

PMID- 10069482
TI  - Effect of Cassava on motor co-ordination and neurotransmitter level in the albino
      rat.
AB  - The root of Cassava, a tropical plant, is consumed in the tropics and has been
      attributed as the cause for various tropical neuropathies. This study aims to
      discover the neurotoxic effects of chronic cassava consumption of Indian origin
      and the effect of malnutrition. The assessment is based on the motor co
      ordination and brain neurotransmitters in rats. Cassava consumption reduced the
      motor co-ordination, but the changes in neurotransmitter levels due to cassava
      consumption (except for 5HT in corpus striatum) was identical with malnutrition
      induced changes, indicating that the toxicity of chronic cassava consumption (of
      Indian origin) is mainly due to the associated protein calorie malnutrition
      (PCM).

PMID- 10069483
TI  - Suppressive effects of josamycin on the development of altered liver cell foci
      and chronic nephropathy in a carcinogenicity study.
AB  - The carcinogenicity of josamycin was examined in Fischer 344 (F344) rats. Groups
      of 50 males and 50 females were given the compound in their diet at
      concentrations of 0 (control), 1.25 or 2.5% for 104-weeks; these dose levels were
      selected on the basis of the results of a subchronic study, in which animals
      rather rejected 5% josamycin. All surviving rats were killed at wk 106. A variety
      of tumours developed in all groups, including the control group, but all the
      neoplastic lesions were histologically similar to those known to occur
      spontaneously in this strain of rats, and no statistically significant increase
      in the incidence of any tumour was found in the treated groups of either sex.
      Interestingly, the josamycin treatment significantly reduced the development of
      altered liver cell foci and chronic nephropathy in a dose-dependent manner. Thus,
      it was concluded that, under the present experimental conditions, josamycin is
      not carcinogenic in F344 rats.

PMID- 10069484
TI  - Cytotoxic and porphyrinogenic effects of diphenyl ethers in cultured rat
      hepatocytes: chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox.
AB  - We studied the cytotoxic and porphyrinogenic effects of four diphenyl ethers
      (DPEs), chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox, in rat
      hepatocytes cultured on Matrigel. Cytotoxicity was determined as a decrease in
      viability measured by the release of lactate dehydrogenase. Of the DPEs examined.
      CNP-amino was the most cytotoxic, with an LC50 value of 0.36 mM (95% confidence
      interval, 0.33-0.40 mM). CNP also reduced the viability in a concentration
      dependent manner at the concentrations of 0.50 mM or above. In contrast, no
      concentration-dependent decrease in viability was observed in the chlomethoxyfen-
      and bifenox-treated hepatocytes at the concentrations up to 1.0 mM. To identify
      the enzyme involved in the metabolic activation of CNP-amino, inhibition studies
      were carried out using SKF 525-A (0.050 mM) and methimazole (1.0 mM). SKF 525-A,
      a cytochrome P450 inhibitor. quickened the onset of cell killing by CNP-amino,
      while methimazole, an inhibitor of flavin-containing monooxygenase (FMO),
      partially suppressed the cytotoxicity of CNP-amino. These results suggest that
      FMO plays an important role in the cytotoxicity induced by CNP-amino, while
      cytochrome P450 participates in the detoxification, possibly via the ring
      hydroxylation. The maximum porphyrin accumulation was observed at 0.13 mM for
      chlomethoxyfen (18-fold) and at 0.25 mM for CNP and bifenox (17- and 21-fold,
      respectively). In contrast to these DPEs, the porphyrinogenic effect of CNP-amino
      was weak, with the maximum accumulation at 0.13 mM (at least fivefold). The
      predominant species was protoporphyrin IX in all of the DPE-treated cultures.
      These results suggest that all of the DPEs examined, possibly including CNP
      amino, inhibit protoporphyrinogen oxidase, resulting in the accumulation of
      protoporphyrin IX.

PMID- 10069485
TI  - Subchronic inhalation toxicity of diglyme.
AB  - Diglyme [1,1'-oxybis(2-methoxyethane)] is an organic solvent belonging to the
      glycol ether class of compounds. To assess the inhalation toxicity of diglyme,
      groups of 20 male and 10 female rats were exposed by nose-only inhalation 6
      hours/day, 5 days/week for 2 weeks to either 0 (control), 110, 370 or 1100 ppm
      diglyme. To compare potency, 2-methoxyethanol was also tested at 300 ppm. Rats
      were sacrificed either immediately following exposure, after a 14-day recovery
      period, or after 42 and 84 days of recovery (males only). Parameters investigated
      included in-life observations and body weights, clinical pathology, and
      histopathology with organ weights. Exposure to diglyme produced a variety of
      concentration-related haematological, clinical chemical and histopathological
      changes in both sexes. The most striking effect produced in all test groups was
      cellular injury involving the testes, seminal vesicles, epididymides and
      prostate. Although these effects were more severe at the higher concentrations
      tested, partial or complete recovery was seen by 84 days post-exposure. Changes
      in the haematopoietic system occurred in both sexes and involved the bone marrow,
      spleen, thymus, leucocytes and erythrocytes. The testicular effects of diglyme
      were somewhat less pronounced than those seen with 2-methoxyethanol. The no
      observed-effect level (NOEL) for repeated inhalation exposure to diglyme in
      female rats is 370 ppm. For males, all concentrations tested produced effects to
      the reproductive system, hence a no-observed-effect level could not be
      demonstrated.

PMID- 10069486
TI  - Development of a non-radioactive endpoint in a modified local lymph node assay.
AB  - A murine local lymph node assay (LLNA) has been developed as an alternative to
      guinea pig models for contact sensitization testing. Although the LLNA appears to
      be a little less sensitive than the most stringent of guinea pig assays, it
      provides a rapid, objective, quantitative and cost-effective method for screening
      strong contact sensitizers and has advantages with respect to animal welfare.
      However, a potential disadvantage is the need for the use of radioactive
      material. We have reported previously that an ex vivo assay based on similar
      principles to the original in vivo LLNA, but using a non-radioactive endopoint,
      was valid for the prediction of strong sensitizers. This ex vivo assay was not
      sensitive enough to allow prediction of moderately potent ones. In this study, we
      propose a new parameter, Corrected IL-2 Index (CII), for the prediction of
      moderate sensitizers. To obtain CII the IL-2 release in the supernatant of the
      cell culture is corrected for lymph node weight ratio and ratio of CD4-positive
      subset. We found that CII predicted the allergenicity of moderate sensitizers,
      including the ones recommended by the OECD in guideline 406, such as
      mercaptobenzothiazole and hexyl cinnamic aldehyde. The allergenicity of metal
      salts, such as potassium dichromate, ammonium tetrachloroplatinate and cobalt
      chloride, was also predicted by the CII. We conclude that the use of CII as an
      index significantly increases the sensitivity of the ex vivo method so that
      moderate sensitizers may also be detected.

PMID- 10069487
TI  - Heat stress aggravates viral myocarditis in mice.
AB  - While a beneficial effect of hyperthermia on viral infection has been
      hypothesized, there are no data on viral myocarditis in vivo. To investigate
      whether hyperthermia might attenuate the course or severity of viral myocarditis,
      we studied the pathological changes in a murine model of viral myocarditis. C3H
      mice were inoculated i.p. with the encephalomyocarditis virus (500 pfu). They
      were anesthetized and heated to a body temperature of 42.5+/-0.2 degrees C for 30
      min. The latter was performed 4 hr before (n=28, HB) or 4 hr after (n=28, HA) the
      viral inoculation; results were compared with nonheated, infected controls (n=30,
      Cont). Cardiac viral titers were recorded on day 3, and the body weight (BW),
      heart weight (HW) and pathological changes were recorded on days 5 and 10. The
      incidence of spontaneous mortality on day 10 was significantly higher in the HA
      group (all deaths occurring by day 7 post-inoculation) as compared with the HB
      (35%) or Cont (18%) groups. Viral titers in the HA group (n=4) were significantly
      (P<0.05) higher than those in the Cont (n=7) or HB (n=7) groups (4.11+/-0.54 vs
      3.01+/-0.44 and 3.23+/-0.45 LogTCID50/mg, respectively). On day 5, the HW, the
      BW/HW ratio, and the severity of myocardial necrosis were all significantly
      higher in the HA than in the Cont and HB groups. To confirm the effect of
      hyperthermia on the expression of heart shock protein (HSP), immunohistochemical
      staining was done in the virus-infected hearts. The nucleus and cytoplasm of the
      injured myocardium in the HA group strongly expressed HSP70, whereas the HB and
      Cont groups were negative for this protein. In conclusion, induction of
      hyperthermia after viral inoculation aggravated the viral-induced myocardial
      necrosis and increased the mortality rate in a murine model of viral myocarditis
      and induced myocardial heat shock protein 70.

PMID- 10069488
TI  - Studies on the antitumor activity and biochemical actions of cyclopentenyl
      cytosine against human colon carcinoma HT-29 in vitro and in vivo.
AB  - Cyclopentenyl cytosine (CPEC) is cytotoxic to several tumor cell lines. CPEC
      inhibits CTP synthesis resulting in depletion of cytidylate pools. The aim of
      this study was to examine CPEC's cytotoxic and antitumor activity in vitro and in
      vivo against human colon carcinoma HT-29, and to relate its action on CTP
      synthesis. CPEC exhibits potent cytotoxicity in vitro to HT-29 cells with an LC50
      (concentration that is lethal to the survival of 50% cell colonies) of 2.4 microM
      and 0.46 microM following 2 h and 24 h exposure, respectively. Incubation of
      cells with CPEC for 2 h resulted in a dose-dependent decrease in cytidylate
      pools. The in vivo antitumor activity of CPEC in athymic mice transplanted
      subcutaneously (s.c.) with 3 million HT-29 cells was examined. Antitumor activity
      of CPEC was elucidated in early-staged tumor, wherein CPEC (1.5 mg/kg, QD x 9 or
      3 mg/kg, QOD x 9) was administered intraperitoneally (i.p.) 24 h after tumor
      implantation and it resulted in a significant reduction in tumor weight to 48% of
      control. The effect of CPEC on established solid tumors in vivo was examined in
      athymic mice transplanted s.c. 14 days earlier with HT-29 cells and treated i.p.
      with 1.5 mg/kg CPEC, QD x 5 for 4 courses, with a 10 day-interval between
      courses. This treatment resulted in a significant reduction in tumor weight (72%)
      in the treated group. HPLC analysis of HT-29 tumor obtained from mice after
      treatment with CPEC showed a depletion of the CTP concentration reaching a nadir
      at 8 h. In conclusion, the present studies demonstrate potent antitumor activity
      of CPEC against freshly transplanted and established human colon carcinoma which
      can be corroborated with the drug's biochemical actions.

PMID- 10069489
TI  - Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic or
      parasympatholytic syndromes induced by reserpine or diphemanil-methylsulfate.
AB  - Parasympathetic hyperactivity is found in some infants presenting faint episodes
      and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore
      it was interesting to look for a noninvasive biochemical indicator of
      parasympathetic activity. A parasympaticomimetic syndrome associated with
      muscarinic receptor stimulation, which has been followed during 48 h, was
      obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and
      a model of prolonged parasympatholytic syndrome, by administration of diphemanil
      methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean
      daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were
      respectively observed. In the reserpine-treated rats we found significantly
      increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and
      T48h, when compared with vehicle-treated controls (+87% in one experiment, +135%
      in the other, when expressed in pmol/microg creatinine); norepinephrine urinary
      excretion between T24h and T48h was decreased (-44%); the increase in cGMP
      urinary excretion was not significantly modified by the NO-synthase inhibitor, L
      nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly
      decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus
      cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated
      rats. The link between these modifications in cGMP excretion and muscarinic
      receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP
      excretion could be tested as screening parameter in infants at risk of faint
      episodes associated with bradycardia.

PMID- 10069490
TI  - Modified natural porcine surfactant modulates tobacco smoke-induced stress
      response in human monocytes.
AB  - Tobacco smoke (TS) is a potent source of oxidants and oxidative stress is an
      important mechanism by which TS exerts its toxicity in the lung. We have shown
      that TS induces heat shock (HS)/stress protein (HSP) synthesis in human
      monocytes. Pulmonary surfactant (PS) whose major physiological function is to
      confer mechanical stability to alveoli, also modulates oxidative metabolism and
      other pro-inflammatory functions of monocytes-macrophages. In order to determine
      whether PS alters the stress response induced by TS, we incubated human
      peripheral blood monocytes overnight with modified natural porcine surfactant
      (Curosurf) (1 mg/ml) before exposure to TS. Curosurf decreased TS-induced, but
      not HS-induced, expression of the major cytosolic, inducible 72 kD HSP (Hsp70).
      Furthermore, TS-generated superoxide anions production was significantly
      decreased by Curosurf in an acellular system, suggesting a direct scavenging
      effect of PS. We also examined the effects of TS and PS on monocytes
      ultrastructure. Monocytes incubated with Curosurf presented smoother cell
      membranes than control monocytes, while TS-induced monocyte vacuolization was, at
      least in part, prevented by Curosurf. Taken together, our data suggest that PS
      plays a protective role against oxygen radical-mediated, TS-induced cellular
      stress responses.

PMID- 10069491
TI  - Association of age-related decrease in platelet membrane fluidity with platelet
      lipid peroxide.
AB  - The influence of age on platelet lipid peroxide (LPO), platelet membrane fluidity
      and the composition of fatty acid was investigated in female Wistar rats widely
      ranging in age from 14 to 720 days old. LPO levels were significantly higher
      (p<0.05) in the platelets of upper age groups than in those of lower age groups,
      showing a significantly positive correlation with age (r=0.84, p<0.0001).
      Membrane fluidity, assessed by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence
      polarization, was significantly reduced with age. The composition of fatty acid
      demonstrated an age-related elevation (p<0.05) in the unsaturation index. The
      rises in the LPO levels revealed a significantly positive correlation with DPH
      polarization (r=0.73, p<0.0001). Thus our results suggested that the age-related
      deterioration of platelet membrane fluidity, despite a significant elevation in
      the unsaturation index, was due to the age-related higher basal levels of LPO in
      platelets.

PMID- 10069492
TI  - Diprotin A, an inhibitor of dipeptidyl aminopeptidase IV(EC 3.4.14.5) produces
      naloxone-reversible analgesia in rats.
AB  - The dipeptidyl aminopeptidase IV (DP IV) inhibitor Diprotin A produces a full,
      dose-dependent, short-lasting and naloxone-reversible analgesia in the rat tail
      flick test when given intracerebroventricularly, with an ED50 of 295 nmol/rat but
      it has no direct opioid agonist activity in the longitudinal muscle strip of
      guinea-pig ileum bioassay. Two of the potential DP IV substrates, morphiceptin
      and endomorphin 1, identified recently in bovine brain were also analgesic given
      by similar route. The action of endomorphin 1 was more potent (ED50 = 7.9
      nmol/rat) and slightly but significantly more sustained than that of Diprotin A.
      Diprotin A neither potentiated nor prolonged the effect of a marginally analgesic
      dose of endomorphin 1. The distinct time course and the lack of potentiation
      indicate that in the analgesic effect of Diprotin A in rats the protection of a
      brain Tyr-Pro-peptide other than endomorphin 1 is involved.

PMID- 10069493
TI  - Effects of ginseng on ethanol induced sedation in mice.
AB  - The effects of ginseng, ginsenosides, coffee, and caffeine on 75% ethanol induced
      sleeping in mice were examined. Mice treated with ethanol lost their righting
      reflex within 30 min and this lasted for about 4 h. The onset time of lose of
      righting reflex (LR) in mice pre-treated with ginseng, ginsenosides, coffee or
      caffeine 10 min before ethanol was significantly delayed; whereas the duration of
      sleep was not affected by all treatments. Administration of these agents 10 min
      after ethanol was ineffective in counteracting the LR effect of ethanol. Coffee
      and caffeine produced central stimulation and increased locomotor activity.
      Ginseng and ginsenosides were found to enhance exercise endurance and reduced the
      plasma level of ethanol. Gastric emptying was slowed by ginseng, ginsenosides or
      ethanol administration. An additive effect was observed when the mice were pre
      treated with ginseng or ginsenosides 10 min before ethanol administration. It is
      suggested that ginseng decreased plasma ethanol concentration by delaying gastric
      emptying and this may be partly due to the effect of the ginsenosides.

PMID- 10069494
TI  - Dextran sulfate inhibits E-selectin-mediated neutrophil adhesion to endotoxin
      activated vascular endothelial cells.
AB  - Effects of heparin-like glycosaminoglycans (h-GAGs) on neutrophil adhesion to
      endothelial cells (ECs) were investigated under physiological flow conditions
      using human umbilical vein ECs. Neutrophil adhesion to lipopolysaccharide
      activated ECs was assayed under rotating conditions with addition of h-GAGs or
      monoclonal antibodies (mAbs) against selectins. Neutrophil adhesion to activated
      ECs under rotating conditions was suppressed completely by anti-E-selectin mAb
      and partially by anti-L-selectin mAb. Addition of dextran sulfate or heparin also
      significantly inhibited neutrophil adhesion to ECs under the same conditions.
      Moreover, effects of h-GAGs on neutrophil adhesion to recombinant E-selectin
      coated plates were analyzed. Anti-E-selectin mAb and dextran sulfate, but not
      heparin, significantly inhibited neutrophil adhesion to E-selectin-coated plates.
      Results suggest that dextran sulfate inhibited E-selectin-mediated neutrophil
      adhesion to endotoxin-activated ECs under physiologic flow conditions.

PMID- 10069495
TI  - Sensitization by chronic diazepam treatment of A2A adenosine receptor-mediated
      relaxation in rat pulmonary artery.
AB  - The effects of a 10-day i.p. treatment of rats with diazepam on responses to
      subtype selective adenosine receptor agonists were studied 3 h, 2 and 8 days
      after termination of diazepam treatment in isolated cardiovascular tissues
      possessing distinct adenosine receptors. After long-lasting diazepam exposure,
      the relaxation elicited by the specific A2A receptor agonist CGS 21680 was
      enhanced in rat main pulmonary arteries (a tissue containing A2A adenosine
      receptors). The increased sensitivity of A2A receptors observed 3 h and 2 days
      after withdrawal of diazepam was completely restored by the 8th day of the wash
      out period. N6-cyclopentyladenosine (CPA)-induced suppression in mechanical
      activity of electrically stimulated rat atrial myocardium (a tissue containing A1
      adenosine receptors) was not altered following diazepam treatment. In order to
      reveal the possible role of inhibition of membrane adenosine transport in the
      effects of diazepam (a moderate inhibitor of membrane adenosine transport), the
      action of a 10-day treatment with dipyridamole or S-(p-nitrobenzyl)-6-thioinosine
      (NBTI; prototypic adenosine uptake inhibitors) was also studied. Dipyridamole or
      NBTI treatment, like diazepam, increased the responsiveness of rat pulmonary
      artery to CGS 21680, but did not influence the cardiodepressive effect of CPA in
      electrically driven left atrial myocardium. The CGS 21680-induced relaxations
      were significantly antagonized by 10 nM ZM 241385 (a selective A2A adenosine
      receptor antagonist) in vessels of diazepam-treated rats. The relaxation
      responses to verapamil were unaltered in pulmonary arteries obtained from animals
      chronically treated with diazepam, dipyridamole or NBTI. These results suggest
      that chronic diazepam treatment is able to enhance the A2A adenosine receptor
      mediated vascular functions, but does not modify the responses mediated via A1
      receptors of rat myocardium, where nucleoside transport inhibitory sites of
      membrane are of a very low density. It is possible that sensitization of A2A
      adenosine receptor-mediated vasorelaxation is due to a long-lasting inhibition of
      membrane adenosine transporter during diazepam treatment.

PMID- 10069496
TI  - Structure-function analysis of muscarinic receptors and their associated G
      proteins.
AB  - Each member of the muscarinic receptor family (M1-M5) can interact only with a
      limited subset of the many structurally closely related heterotrimeric G proteins
      expressed within a cell. To understand how this selectivity is achieved at a
      molecular level, we have used the G(i/0)-coupled M2 and the Gq/11-coupled M3
      muscarinic receptors as model systems. We developed a genetic strategy involving
      the coexpression of wild type or mutant muscarinic receptors with hybrid or
      mutant G protein alpha subunits to identify specific, functionally relevant
      receptor/G protein contact sites. This approach led to the identification of N-
      and C-terminal amino acids on alpha(q) and alpha(i) that are critical for
      maintaining proper receptor/G protein coupling. Moreover, several receptor sites
      were identified that are likely to be contacted by these functionally critical G
      alpha residues. To gain deeper insight into muscarinic receptor structure, we
      recently developed a cysteine disulfide cross-linking strategy, using the M3
      muscarinic receptor as a model system. Among other structural modifications, this
      approach involves the removal of most native cysteine residues by site-directed
      mutagenesis, the insertion of three factor Xa cleavage sites into the third
      intracellular loop, and systematic 'reintroduction' of pairs of cysteine
      residues. Following treatment of receptor-containing membrane preparations with
      factor Xa and oxidizing agents, disulfide cross-linked products can be identified
      by immunoprecipitation and immunoblotting studies. This approach should greatly
      advance our knowledge of the molecular architecture of muscarinic and other G
      protein-coupled receptors.

PMID- 10069497
TI  - Molecular events associated with the regulation of signaling by M2 muscarinic
      receptors.
AB  - Multiple events are associated with the regulation of signaling by the M2
      muscarinic cholinergic receptors (mAChRs). Desensitization of the attenuation of
      adenylyl cyclase by the M2 mAChRs appears to involve agonist-dependent
      phosphorylation of M2 mAChRs by G-protein coupled receptor kinases (GRKs) that
      phosphorylate the receptors in a serine/threonine rich motif in the 3rd
      intracellular domain of the receptors. Mutation of residues 307-311 from TVSTS to
      AVAAA in this domain of the human M2 mAChR results in a loss of receptor/G
      protein uncoupling and a loss of arrestin binding. Agonist-induced sequestration
      of receptors away from their normal membrane environment is also regulated by
      agonist-induced phosphorylation of the M2 mAChRs on the 3rd intracellular domain,
      but in HEK cells, the predominant pathway of internalization is not regulated by
      GRKs or arrestins. This pathway of internalization is not inhibited by a dominant
      negative dynamin, and does not appear to involve either clathrin coated pits or
      caveolae. The signaling of the M2 mAChR to G-protein regulated inwardly
      rectifying K channels (GIRKs) can be modified by RGS proteins. In HEK cells,
      expression of RGS proteins leads to a constitutive activation of the channels
      through a mechanism that depends on Gbetagamma. RGS proteins appear to increase
      the concentration of free Gbetagamma in addition to acting as GAPs. Thus multiple
      mechanisms acting at either the level of the M2 mAChRs or the G-proteins can
      contribute to the regulation of signaling via the M2 mAChRs.

PMID- 10069498
TI  - The influence of the cellular context on receptor function: a necessary
      consideration for physiologic interpretations of receptor expression studies.
AB  - The cell model studied has a fundamental influence on the function and regulation
      of G protein linked receptors. These cell-dependent effects are illustrated in
      the current communication focusing on M3 muscarinic, CCK and GRP receptors.
      Receptors interact with multiple cellular mechanisms. The most obvious are those
      involved in coupling to signaling mechanisms such as G proteins. Receptors are
      themselves phosphorylated and dephosphorylated by cellular kinases and
      phosphatases. Receptors may sequester, internalize, down-regulate and recycle via
      interactions with a number of separate cellular mechanisms. When the number and
      complexity of interactions between the cell and the receptor are taken into
      account it is not surprising that the cell model has a primary influence on
      receptor function and regulation. The implications of the importance of the cell
      model in receptor function for studies aimed at answering physiologic questions
      are discussed.

PMID- 10069499
TI  - Molecular analysis of the regulation of muscarinic receptor expression and
      function.
AB  - We have investigated the molecular mechanisms involved in the regulation of
      muscarinic acetylcholine receptor gene expression and localization and generated
      knockout mice to study the role of the M1 muscarinic receptor in vivo. We have
      used the MDCK cell system to demonstrate that different subtypes of mAChR can be
      targeted to different regions of polarized cells. We have also examined the
      developmental regulation of mAChR expression in the chick retina. Early in
      development, the M4 receptor is the predominant mAChR while the levels of the M2
      and M3 receptors increase later in development. The level of M2 receptor is also
      initially very low in retinal cultures and undergoes a dramatic increase over
      several days in vitro. The level of M2 receptor can be increased by a potentially
      novel, developmentally regulated, secreted factor produced by retinal cells. The
      promoter for the chick M2 receptor gene has been isolated and shown to contain a
      site for GATA-family transcription factors which is required for high level
      cardiac expression. The M2 promoter also contains sites which mediate induction
      of transcription in neural cells by neurally active cytokines. We have generated
      knockout mice lacking the M1 receptor and shown that these mice do not exhibit
      pilocarpine-induced seizures and muscarinic agonist-induced suppression of the M
      current potassium channel in sympathetic neurons.

PMID- 10069500
TI  - Development of muscarinic receptors and regulation of secretory responsiveness in
      rodent sweat glands.
AB  - Sweat glands are innervated by sympathetic neurons which undergo a change in
      transmitter phenotype from noradrenergic to cholinergic during development. As
      soon as the glands begin to differentiate, M3 muscarinic receptor mRNA and
      binding sites are detectable. Receptor expression appears in the absence of
      innervation and is maintained after denervation. While receptor expression is not
      regulated by innervation, secretory responsiveness is. Muscarinic blockade during
      development or in adult animals results in the loss of responsiveness and its
      reappearance requires several days. Cholinergic muscarinic activation is most
      likely to regulate one or more steps in the signalling cascade that are
      downstream of calcium mobilization. The anterograde regulation of sweat gland
      responsiveness is one facet of the reciprocal interactions are required to
      establish a functional synapse in this system.

PMID- 10069501
TI  - Contractile role of M2 and M3 muscarinic receptors in gastrointestinal smooth
      muscle.
AB  - Muscarinic agonists elicit contraction through M3 receptors in most isolated
      preparations of gastrointestinal smooth muscle, and not surprisingly, several
      investigators have identified M3 receptors in smooth muscle using biochemical,
      immunological and molecular biological methods. However, these studies have also
      shown that the M2 receptor outnumbers the M3 by a factor of about four in most
      instances. In smooth muscle, M3 receptors mediate phosphoinositide hydrolysis and
      Ca2+ mobilization, whereas M2 receptors mediate an inhibition of cAMP
      accumulation. The inhibitory effect of the M2 receptor on cAMP levels suggests an
      indirect role for this receptor; namely, an inhibition of the relaxant action of
      cAMP-stimulating agents. Such a function has been rigorously demonstrated in an
      experimental paradigm where gastrointestinal smooth muscle is first incubated
      with 4-DAMP mustard to inactivate M3 receptors during a Treatment Phase, and
      subsequently, the contractile activity of muscarinic agonists is characterized
      during a Test Phase in the presence of histamine and a relaxant agent. When
      present together, histamine and the relaxant agent (e.g., isoproterenol or
      forskolin) have no net contractile effect because their actions oppose one
      another. However, under these conditions, muscarinic agonists elicit a highly
      potent contractile response through the M2 receptor, presumably by inhibiting the
      relaxant action of isoproterenol or forskolin on histamine-induced contractions.
      This contractile response is pertussis toxin-sensitive, unlike the standard
      contractile response to muscarinic agonists, which is pertussis toxin
      insensitive. When measured under standard conditions (i.e., in the absence of
      histamine and without 4-DAMP mustard-treatment), the contractile response to
      muscarinic agonists is moderately sensitive to pertussis toxin if isoproterenol
      or forskolin is present. Also, pertussis toxin-treatment enhances the relaxant
      action of isoproterenol in the field-stimulated guinea pig ileum. These results
      demonstrate that endogenous acetylcholine can activate M2 receptors to inhibit
      the relaxant effects of beta-adrenoceptor activation on M3 receptor-mediated
      contractions. An operational model for the interaction between M2 and M3
      receptors shows that competitive antagonism of the interactive response resembles
      an M3 profile under most conditions, making it difficult to detect the
      contribution of the M2 receptor.

PMID- 10069502
TI  - Muscarinic antagonists in development for disorders of smooth muscle function.
AB  - Compounds with high affinity for muscarinic M3 receptors have been used for many
      years to treat conditions associated with altered smooth muscle tone or
      contractility such as urinary urge incontinence, irritable bowel syndrome or
      chronic obstructive airways disease. M3 selective antagonists have the potential
      for improved toleration when compared with non-selective compounds. Darifenacin
      has high affinity (pKi 9.12) and selectivity (9 to 74-fold) for the human cloned
      muscarinic M3 receptor. Consistent with this profile, the compound potently
      inhibited M3 receptor mediated responses of smooth muscle preparations (guinea
      pig ileum, trachea and bladder, pA2 8.66 to 9.4) with selectivity over responses
      mediated through the M1 (pA2 7.9) and M2 receptors (pA2 7.48). Interestingly,
      darifenacin also exhibited functional tissue selectivity for intestinal smooth
      muscle over the salivary gland. The M3 over M1 and M2 selectivity of darifenacin
      was confirmed in a range of animal models. In particular, in the conscious dog
      darifenacin inhibited intestinal motility at doses lower than those which inhibit
      gastric acid secretion (M1 response), increase heart rate (M2 response) or
      inhibit salivary secretion. Clinical studies are ongoing to determine if
      darifenacin has improved efficacy and or toleration when compared with non
      selective agents.

PMID- 10069503
TI  - Neuronal soma-dendritic and prejunctional M1-M4 receptors in gastrointestinal and
      genitourinary smooth muscle.
AB  - A variety of neurons in gastrointestinal and genitourinary smooth muscle express
      muscarinic auto- as well as heteroreceptors. These receptors are found on the
      soma and dendrites of many cholinergic, sympathetic and NANC neurons and on axon
      terminals. A given neuron may contain both excitatory and inhibitory presynaptic
      muscarinic receptors. The subtypes involved are species- and tissue-dependent,
      and neuronal M1 to M4 receptors have been shown to be expressed in smooth muscle
      tissues. In this study, the ability of several selective muscarinic receptor
      antagonists to inhibit the effect of arecaidine propargyl ester (APE) on
      prejunctional muscarinic receptors on sympathetic nerve endings in the rabbit
      anococcygeus muscle (RAM) was investigated to characterise the receptor subtype
      involved. Electrical field stimulation (EFS) resulted in a release of
      noradrenaline (NA) eliciting monophasic contractions due to stimulation of
      postjunctional alpha1-adrenoceptors. The selective muscarinic agonist APE did not
      reduce contractions to exogenous NA, but caused a concentration-related and N
      methylatropine-sensitive inhibition of neurogenic responses. All muscarinic
      antagonists investigated failed to affect the EFS-induced contractions, but
      shifted the concentration-response curve of APE to the right in a parallel and
      surmountable fashion. Schild analysis yielded regression lines of unit slope,
      indicating competitive antagonism. The following rank order of antagonist
      potencies (pA2 values) was found: tripitramine (9.10) > AQ-RA 741 (8.26) > or =
      himbacine (8.04) > or = (S)-dimethindene (7.69) > pirenzepine (6.46) > or = p-F
      HHSiD (6.27). A comparison of the pA2 values determined in the present study with
      literature binding and functional affinities obtained at native or recombinant M1
      to M5 receptors strongly suggests that NA release from sympathetic nerve endings
      in RAM is inhibited by activation of prejunctional muscarinic M2 receptors.

PMID- 10069504
TI  - Function, signal transduction mechanisms and plasticity of presynaptic muscarinic
      receptors in the urinary bladder.
AB  - Presynaptic M1 muscarinic receptors on parasympathetic nerve terminals in rat
      urinary bladder strips are involved in an autofacilitatory mechanism that
      markedly enhances acetylcholine release during continuous electrical field
      stimulation. The facilitatory muscarinic mechanism is dependent upon a PKC
      mediated second messenger pathway and influx of extracellular Ca2+ into the
      parasympathetic nerve terminals via L and N-type Ca2+ channels. Prejunctional
      muscarinic facilitation has also been detected in human bladders. The muscarinic
      facilitatory mechanism is upregulated in hyperactive bladders from chronic spinal
      cord transected rats; and the facilitation in these preparations is primarily
      mediated by M3 muscarinic receptors. Presynaptic muscarinic receptors represent a
      new target for pharmacological treatment of bladder hyperactivity. If presynaptic
      facilitation is restricted to the bladder and not present in other tissues then
      drugs acting at this site might be expected to exhibit uroselectivity.

PMID- 10069505
TI  - Muscarinic receptor subtypes modulating smooth muscle contractility in the
      urinary bladder.
AB  - Normal physiological voiding as well as generation of abnormal bladder
      contractions in diseased states is critically dependent on acetylcholine-induced
      stimulation of contractile muscarinic receptors on the smooth muscle (detrusor)
      of the urinary bladder. Muscarinic receptor antagonists are efficacious in
      treating the symptoms of bladder hyperactivity, such as urge incontinence,
      although the usefulness of available drugs is limited by undesirable side
      effects. Detrusor smooth muscle is endowed principally with M2 and M3 muscarinic
      receptors with the former predominating in number. M3 muscarinic receptors,
      coupled to stimulation of phosphoinositide turnover, mediate the direct
      contractile effects of acetylcholine in the detrusor. Emerging evidence suggests
      that M2 muscarinic receptors, via inhibition of adenylyl cyclase, cause smooth
      muscle contraction indirectly by inhibiting sympathetically (beta-adrenoceptor)
      mediated relaxation. In certain diseased states, M2 receptors may also contribute
      to direct smooth muscle contraction. Other contractile mechanisms involving M2
      muscarinic receptors, such as activation of a non-specific cationic channel and
      inactivation of potassium channels, may also be operative in the bladder and
      requires further investigation. From a therapeutic standpoint, combined blockade
      of M2 and M3 muscarinic receptors would seem to be ideal since this approach
      would evoke complete inhibition of cholinergically-evoked smooth muscle
      contractions. However, if either the M2 or M3 receptor assumes a greater
      pathophysiological role in disease states, then selective antagonism of only one
      of the two receptors may be the more rational approach. The ultimate therapeutic
      strategy is also influenced by the extent to which pre-junctional M1 facilitatory
      and M2 inhibitory muscarinic receptors regulate acetylcholine release and also
      which subtypes mediate the undesirable effects of muscarinic receptor blockade
      such as dry mouth. Finally, the consequence of muscarinic receptor blockade in
      the central nervous system on the micturition reflex, an issue which is poorly
      studied and seldom taken into consideration, should not be ignored.

PMID- 10069506
TI  - M2 receptors in genito-urinary smooth muscle pathology.
AB  - In vitro bladder contractions in response to cumulative carbachol doses were
      measured in the presence of selective muscarinic antagonists from rats which had
      their major pelvic ganglion bilaterally removed (denervation, DEN) or from rats
      in which the spinal cord was injured (SCI) via compression. DEN induced both
      hypertrophy (505+/-51 mg bladder weight) and a supersensitivity of the bladders
      to carbachol (EC50=0.7+/-0.1 uM). Some of the SCI rats regained the ability to
      void spontaneously (SPV). The bladders of these animals weighed 184+/-17 mg,
      significantly less than the bladders of non voiding rats (NV, 644+/-92 mg). The
      potency of carbachol was greater in bladder strips from NV SCI animals
      (EC50=0.54+/-0.1 uM) than either bladder strips from SPV SCI (EC50=0.93+/-0.3
      microM), DEN or control (EC50=1.2+/-0.1 microM) animals. Antagonist affinities in
      control bladders for antagonism of carbachol induced contractions were consistent
      with M3 mediated contractions. Antagonist affinities in DEN bladders for 4
      diphenlacetoxy-N-methylpiperidine methiodide (4-DAMP, 8.5) and para fluoro
      hexahydrosilodifenidol (p-F-HHSiD, 6.6); were consistent with M2 mediated
      contractions, although the methoctramine affinity (6.5) was consistent with M3
      mediated contractions. p-F-HHSiD inhibited carbachol induced contraction with an
      affinity consistent with M2 receptors in bladders from NV SCI (pKb=6.4) animals
      and M3 receptors in bladders from SPV SCI animals (pKb=7.9). Subtype selective
      immunoprecipitation of muscarinic receptors revealed an increase in total and an
      increase in M2 receptor density with no change in M3 receptor density in bladders
      from DEN and NV SCI animals compared to normal or sham operated controls. M3
      receptor density was lower in bladders from SPV SCI animals while the M2 receptor
      density was not different from control. This increase in M2 receptor density is
      consistent with the change in affinity of the antagonists for inhibition of
      carbachol induced contractions and may indicate that M2 receptors or a
      combination of M2 and M3 receptors directly mediate smooth muscle contraction in
      bladders from DEN and NV SCI rats.

PMID- 10069507
TI  - M2 signaling in smooth muscle cells.
AB  - M2 receptor stimulation results in the gating of nonselective cation channels in
      several smooth muscle cell types. However the requirement for current activation
      includes a rise in cytosolic calcium mediated by M3 receptor induced calcium
      release. This complex signaling system confers substantial complexity on the
      interpretation of pharmacological experiments. M2 and M3 receptor stimulation has
      also been linked to the inhibition of potassium channels in smooth muscle. These
      signaling events are likely to play important roles in excitation/contraction
      coupling.

PMID- 10069508
TI  - Role of M2 muscarinic receptors in airway smooth muscle contraction.
AB  - Airway smooth muscle expresses both M2 and M3 muscarinic receptors with the
      majority of the receptors of the M2 subtype. Activation of M3 receptors, which
      couple to Gq, initiates contraction of airway smooth muscle while activation of
      M2 receptors, which couple to Gi, inhibits beta-adrenergic mediated relaxation.
      Increased sensitivity to intracellular Ca2+ is an important mechanism for agonist
      induced contraction of airway smooth muscle but the signal transduction pathways
      involved are uncertain. We studied Ca2+ sensitization by acetylcholine (ACh) and
      endothelin-1 (ET-1) in porcine tracheal smooth muscle by measuring contractions
      at constant [Ca2+] in strips permeabilized with Staphylococcal alpha-toxin. Both
      ACh and ET-1 contracted airway smooth muscle at constant [Ca2+]. Pretreatment
      with pertussis toxin for 18-20 hours reduced ACh contractions, but had no effect
      on those of ET-1 or GTPgammaS. We conclude that the M2 muscarinic receptor
      contributes to airway smooth muscle contraction at constant [Ca2+] via the
      heterotrimeric G-protein Gi.

PMID- 10069509
TI  - Effects of inflammatory cells on neuronal M2 muscarinic receptor function in the
      lung.
AB  - In the lungs, acetylcholine released from the parasympathetic nerves stimulates
      M3 muscarinic receptors on airway smooth muscle inducing contraction and
      bronchoconstriction. The amount of acetylcholine released from these nerves is
      limited locally by neuronal M2 muscarinic receptors. These neuronal receptors are
      dysfunctional in asthma and in animal models of asthma. Decreased M2 muscarinic
      receptor function results in increased release of acetylcholine and in airway
      hyperreactivity. Inflammation has long been associated with hyperreactivity and
      the role of inflammatory cells in loss of neuronal M2 receptor function has been
      examined. There are several different mechanisms for loss of neuronal M2 receptor
      function. These include blockade by endogenous antagonists such as eosinophil
      major basic protein, decreased expression of M2 receptors following infection
      with viruses or exposure to pro inflammatory cytokines such as gamma interferon.
      Finally, the affinity of acetylcholine for these receptors can be decreased by
      exposure to neuraminidase.

PMID- 10069510
TI  - Tiotropium (Spiriva): mechanistical considerations and clinical profile in
      obstructive lung disease.
AB  - Inhaled antimuscarinics, often called anticholinergics in clinical medicine, are
      established as first line bronchodilators in COPD. Tiotropium has been developed
      as a new generation antimuscarinic following ipratropium. Tiotropium is a
      specific, highly potent antimuscarinic, demonstrating very slow dissociation from
      muscarinic receptors. Dissociation from M2-receptors is faster than from M3 or
      M1, which in functional in vitro studies, appeared as kinetic receptor subtype
      selectivity of M3 and M1 over M2. The high potency and slow receptor dissociation
      found its clinical correlate in significant and long lasting bronchodilatation
      and bronchoprotection in patients with COPD and asthma. In asthma, protection
      against methacholine challenge exceeded the study period of 48 hours. In COPD,
      bronchodilatation of about 80% of the plateau was demonstrated after the first
      dose. Following chronic once daily inhalation for 28 days, the improvement in
      pulmonary function was sustained and there was a further increase in peak
      effects, but more importantly a rising baseline, achieving steady state within 2
      weeks. Tiotropium achieves very stable long lasting effects with comparatively
      low variation of bronchodilatation between peak and trough (the level before the
      next administration). Stable 24 hour effectiveness profiles the compound as the
      first once daily bronchodilator. Clinical correlates of kinetic receptor subtype
      selective blockade remain to be shown. Plasma levels of tiotropium at trough are
      in the low pg/ml range and are unlikely to explain the sustained effectiveness in
      the airways. Slow dissociation from muscarinic receptors is likely to be
      responsible for the long duration of action.

PMID- 10069511
TI  - Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy
      display non-desensitized agonist-like effects.
AB  - Circulating autoantibodies against the human M2 muscarinic receptors have been
      previously shown in 38% of patients with idiopathic dilated cardiomyopathy. The
      functional properties of these autoantibodies are reported herein. They were able
      to decrease the cell beating frequency of myocytes in cultured neonatal rat heart
      cells in a dose-dependent manner without desensitization over a period of more
      than 5 hours whereas the non-specific muscarinic receptor agonist carbachol also
      inhibited the heart cell beating frequency but was desensitized within 1 hour. In
      the same cell culture, anti-M2 muscarinic receptor autoantibodies were not able
      to induce internalization of muscarinic receptor whereas carbachol did. These
      results demonstrate for the first time that anti-M2 muscarinic receptor
      autoantibodies from patients with idiopathic dilated cardiomyopathy have
      stimulatory muscarinic activity in vitro, which differ from normal muscarinic
      agonists by non-desensitization.

PMID- 10069512
TI  - Muscarinic cholinergic signaling in cardiac myocytes: dynamic targeting of M2AChR
      to sarcolemmal caveolae and eNOS activation.
AB  - The isoform of nitric oxide synthase (eNOS or NOS3) originally described in
      endothelial cells is also expressed in a number of other cell types, including
      cardiac myocytes. eNOS is activated in both atrial and ventricular myocytes,
      including specialized pacemaker cells, by M2AChR agonists, among other stimuli.
      In cardiac myocytes, as in endothelial cells, eNOS is targeted to sarcolemmal
      caveolae, due to both co-translational myristoylation and later palmitoylation,
      and by the presence of a caveolin binding domain in eNOS which interacts with the
      caveolin scaffolding domain. In the absence of ligand, the M2AChR is not
      associated with caveolar microdomains, but translates into caveolae upon agonist
      (but not antagonist) binding. Finally, the role of M2AChR-induced eNOS activation
      in regulating I(Ca-L) via activation of guanylyl cyclase has been confirmed in
      ventricular myocytes of mice that lack functional eNOS (i.e., eNOS(null)).

PMID- 10069513
TI  - Control elements of muscarinic receptor gene expression.
AB  - Studies describing the structures of the M1, M2 and M4 muscarinic acetylcholine
      receptors (mAChR) genes and the genetic elements that control their expression
      are reviewed. In particular, we focus on the role of the neuron-restrictive
      silencer element/restriction element-1 (NRSE/RE-1) in the regulation of the M4
      mAChR gene. The NRSE/RE-1 was first identified as a genetic control element that
      prevents the expression of the SCG-10 and type II sodium channel (NaII) genes in
      non-neuronal cells in culture. The NRSE/RE-1 inhibits gene expression by binding
      the repressor/silencer protein NRSF/REST, which is present in many non-neuronal
      cell lines and tissues. Our studies show that although the expression of the M4
      mAChR gene is inhibited by NRSF/REST, this inhibition is not always complete.
      Rather, the efficiency of silencing by NRSF/REST is different in different cells.
      A plausible explanation for this differential silencing is that the NRSF/RE-1
      interacts with distinct sets of promoter binding proteins in different types of
      cells. We hypothesize that modulation of NRSF/REST silencing activity by these
      proteins contributes to the cell-specific pattern of expression of the M4 mAChR
      in neuronal and non-neuronal cells. Recent studies that suggest a more complex
      role for the NRSE/RE-1 in regulating gene expression are also discussed.

PMID- 10069514
TI  - Endocytosis and recycling of muscarinic receptors.
AB  - Agonist stimulation causes the endocytosis of many G protein-coupled receptors,
      including muscarinic acetylcholine receptors. In this study we have investigated
      the agonist-triggered trafficking of the M3 muscarinic receptor expressed in SH
      SY5Y human neuroblastoma cells. We have compared the ability of a series of
      agonists to generate the second messenger Ins(1,4,5)P3 with their ability to
      stimulate receptor endocytosis. We show that there is a good correlation between
      the intrinsic activity of the agonists and their ability to increase the rate
      constant for receptor endocytosis. Furthermore, on the basis of our results, we
      predict that even very weak partial agonists should under some circumstances be
      able to cause substantial receptor internalization. Receptor endocytosis occurs
      too slowly to account for the rapid desensitization of the Ca2+ response to
      carbachol. Instead, receptor endocytosis and recycling appear to play an
      important role in resensitization. After an initial agonist challenge, the
      response to carbachol is fully recovered when only about half of the receptors
      have been recycled to the cell surface, suggesting that there is a receptor
      reserve of about 50%. Removal of this reserve by receptor alkylation
      significantly reduces the extent of resensitization. Resensitization is also
      reduced by inhibitors of either endocytosis alone (concanavalin A) or of
      endocytosis and recycling (nigericin). Finally, the protein phosphatase inhibitor
      calyculin A also reduces resensitization, possibly by blocking the
      dephosphorylation of the receptors in an endosomal compartment.

PMID- 10069515
TI  - Repression and activation of muscarinic receptor genes.
AB  - The specific cellular response to muscarinic receptor activation is dependent
      upon appropriate expression of each of the five muscarinic receptor genes by
      individual cells. Here we summarise recent work describing some of the genomic
      regulatory elements and transcriptional mechanisms that control expression of the
      M1 and M4 genes.

PMID- 10069516
TI  - Muscarinic receptor subtypes involved in hippocampal circuits.
AB  - Muscarinic receptors modulate hippocampal activity in two main ways: inhibition
      of synaptic activity and enhancement of excitability of hippocampal cells. Due to
      the lack of pharmacological tools, it has not been possible to identify the
      individual receptor subtypes that mediate the specific physiological actions that
      underlie these forms of modulation. Light and electron microscopic
      immunocytochemistry using subtype-specific antibodies was combined with lesioning
      techniques to examine the pre- and postsynaptic location of m1-m4 mAChR at
      identified hippocampus synapses. The results revealed striking differences among
      the subtypes, and suggested different ways that the receptors modulate excitatory
      and inhibitory transmission in distinct circuits. Complementary physiological
      studies using m1-toxin investigated the modulatory effects of this subtype on
      excitatory transmission in more detail. The implications of these data for
      understanding the functional roles of these subtypes are discussed.

PMID- 10069517
TI  - Using single photon emission tomography (SPECT) and positron emission tomography
      (PET) to trace the distribution of muscarinic acetylcholine receptor (MACHR)
      binding radioligands.
AB  - Two [18F] labeled ligands for the mAChR were prepared and evaluated in rodents
      and nonhuman primates. The properties of both compounds, one an agonist and the
      other an antagonist, were consistent with M2 subtype specificity.

PMID- 10069518
TI  - Allosteric effects of four stereoisomers of a fused indole ring system with 3H-N
      methylscopolamine and acetylcholine at M1-M4 muscarinic receptors.
AB  - We previously demonstrated that brucine and some analogues allosterically enhance
      the affinity of ACh at muscarinic receptor subtypes M1, M3 or M4. Here we
      describe allosteric effects at human M1-M4 receptors of four stereoisomers of a
      pentacyclic structure containing features of the ring structure of brucine. All
      compounds inhibited 3H-NMS dissociation almost completely at all subtypes with
      slopes of 1, with similar affinity values at the 3H-NMS-occupied receptor to
      those estimated from equilibrium assays, consistent with the ternary complex
      allosteric model. Compound 1a showed positive cooperativity with H-NMS and small
      negative or neutral cooperativity with ACh at all subtypes. Its stereoisomer, 1b,
      showed strong negative cooperativity with both 3H-NMS and ACh across the
      subtypes. Compound 2a was positive with 3H-NMS at M2 and M4 receptors, neutral at
      M3 and negative at M1 receptors; it was negatively cooperative with ACh at all
      subtypes. Its stereoisomer, 2b, was neutral with 3H-NMS at M1 receptors and
      positive at the other subtypes; 2b was negatively cooperative with ACh at M1, M3
      and M4 receptors but showed 3-fold positive cooperativity with ACh at M2
      receptors. This latter result was confirmed with further 3H-NMS and 3H-ACh
      radioligand binding assays and with functional assays of ACh-stimulated 35S
      GTPgammaS binding. These results provide the first well characterised instance of
      a positive enhancer of ACh at M2 receptors, and illustrate the difficulty of
      predicting such an effect.

PMID- 10069519
TI  - Potential role of muscarinic receptors in schizophrenia.
AB  - The role of muscarinic receptors in schizophrenia was investigated using the
      muscarinic agonist PTAC. PTAC was highly selective for muscarinic receptors, was
      a partial agonist at muscarinic M2/M4 receptors and an antagonist at M1, M3 and
      M5 receptors. PTAC was highly active in animal models predictive of antipsychotic
      behavior including inhibition of conditioned avoidance responding in rats and
      blockade of apomorphine-induced climbing behavior in mice. d-Amphetamine-induced
      Fos expression in rat nucleus accumbens was inhibited by PTAC, thus directly
      demonstrating the ability of PTAC to modulate DA activity. In
      electrophysiological studies in rats, PTAC acutely inhibited the firing of A10 DA
      cells and after chronic administration decreased the number of spontaneously
      firing DA cells in the A10 brain area. However, PTAC did not appreciably alter
      the firing of A9 DA cells. Thus, PTAC appears to have novel antipsychotic-like
      activity and these data suggest that muscarinic compounds such as PTAC may
      represent a new class of antipsychotic agents.

PMID- 10069520
TI  - SCH 57790: a novel M2 receptor selective antagonist.
AB  - As a decrease in cholinergic neurons has been observed in Alzheimer's Disease
      (AD), therapeutic approaches to AD include inhibition of acetylcholinesterase to
      increase acetylcholine levels. Evidence suggests that acetylcholine release in
      the CNS is modulated by negative feedback via presynaptic M2 receptors, blockade
      of which should provide another means of increasing acetylcholine release.
      Structure-activity studies of [4-(phenylsulfonyl)phenyl]methylpiperazines led to
      the synthesis of 4-cyclohexyl-alpha-[4-[[4-methoxyphenyl]sulfinyl]-phenyl]-1
      piperazin eacetonitrile. This compound, SCH 57790, binds to cloned human M2
      receptors expressed in CHO cells with an affinity of 2.78 nM; the affinity at M1
      receptors is 40-fold lower. SCH 57790 is an antagonist at M2 receptors expressed
      in CHO cells, as the compound blocks the inhibition of adenylyl cyclase activity
      mediated by the muscarinic agonist oxotremorine. This compound should be useful
      in assessing the potential of M2 receptor blockade for enhancement of cognition.

PMID- 10069521
TI  - Cholinergic facilitation of trace eyeblink conditioning in aging rabbits.
AB  - The hippocampus is importantly involved in learning and memory, and is severely
      impacted by aging. In in vitro hippocampal slices, both the post-burst
      afterhyperpolarization (AHP) and spike-frequency accommodation are reduced in
      hippocampal pyramidal neurons after hippocampally-dependent trace eyeblink
      conditioning, indications of increased cellular excitability. The AHP results
      from the activation of outward potassium currents, including sI(AHP) and
      muscarine-sensitive I(M). The AHP is significantly increased in aging hippocampal
      neurons, potentially contributing to age-associated learning deficits. Compounds
      which reduce the AHP and spike-frequency accommodation could facilitate learning
      in normal aging or in age-associated dementias such as Alzheimer's disease. The
      cholinesterase inhibitor metrifonate enhances trace eyeblink conditioning by
      aging rabbits and reduces the AHP and accommodation in hippocampal CA1 neurons in
      a dose-dependent manner. These reductions are mediated by muscarinic cholinergic
      transmission as they are blocked by atropine. Hippocampal neurons from
      metrifonate treated but behaviorally naive rabbits were more excitable and not
      desensitized to the effects of metrifonate since the AHP and accommodation were
      further reduced when metrifonate was bath applied to the neurons. These
      observations suggest that the facilitating effect of chronic metrifonate on
      acquisition of hippocampally dependent tasks is mediated at least partially by
      increasing the baseline excitability of CA1 pyramidal neurons. The issue of
      whether learning can be facilitated with muscarinic cholinergic agonists, in
      addition to cholinesterase inhibitors, was addressed by training aging rabbits
      during intravenous treatment with the M1 agonist CI1017. A dose-dependent
      enhancement of acquisition was observed, with rabbits receiving 1.0 or 5.0 mg/ml
      CI1017 showing comparably improved learning rates as those receiving 0.5 mg/ml or
      vehicle. Sympathetic side effects, mainly excess salivation, were seen with the
      5.0 mg/ml dose. Post-training evaluations suggested that the effective doses of
      CI1017 were enhancing responsivity to the tone conditioned stimulus. These
      studies suggest that muscarinic cholinergic neurotransmission is importantly
      involved in associative learning; that learning in aging animals may be
      facilitated by enhancing cholinergic transmission; and that the facilitation may
      be mediated through actions on hippocampal neurons.

PMID- 10069522
TI  - Muscarinic-mediated analgesia.
AB  - Systemic administration of cholinesterase inhibitors which cross the blood brain
      barrier have long been known to produce analgesia and enhance analgesia from
      opiates. A major site of analgesic action of cholinergic agents is the spinal
      cord. Muscarinic receptors are concentrated in the superficial layers of the
      dorsal horn of the spinal cord, an area of noxious sensory processing, and these
      reflect innervation primarily from cholinergic neurons with cell bodies deep in
      the neck of the dorsal horn. Spinal injection of cholinergic agonists results in
      analgesia which primarily reflects muscarinic receptor activation. Analgesia
      occurs in animal models of acute noxious stimulation and of chronic
      hypersensitivity pain. Although no cholinergic agonists have been tested for
      safety in humans, the cholinesterase inhibitor, neostigmine, has undergone such
      testing, and produces analgesia to experimental, acute postoperative, and chronic
      pain. Thus, muscarinic cholinergic agonists and cholinesterase inhibitors hold
      promise as non-opiate agents for the treatment of moderate to severe acute and
      chronic pain.

PMID- 10069523
TI  - Effects of palmatine on isometric force and intracellular calcium levels of
      arterial smooth muscle.
AB  - The effects of palmatine on isometric force and intracellular free calcium levels
      ([Ca2+]i) were determined in isolated rat arterial strips. Palmatine dose
      dependently relaxed the contractile responses stimulated by phenylephrine (PE) in
      aortic strips. In contrast, it only partially relaxed aortic strips contracted by
      51 mM KCl. Pretreatment with palmatine shifted the dose-response curves of PE
      both rightwards and downwards in a dose-dependent manner. When Ca2+-free solution
      and re-addition of Ca2+ were applied to assess PE-induced phasic and tonic
      contractions, palmatine was found to be effective in inhibiting both
      contractions. The effects of palmatine on intracellular calcium levels were
      measured with the bioluminescent calcium indicator aequorin in rat tail artery
      strips. Palmatine caused a concomitant, dose-dependent decrease in PE-activated
      isometric force and [Ca2+]i, resulting in small changes in the [Ca2+]i-force
      relationship. These results suggest that vasodilatory effect of palmatine was
      mediated by reducing [Ca2+]i as well as affecting [Ca2+]i sensitivity of the
      contractile apparatus. Palmatine-induced [Ca2+]i decreases appeared to involve
      decreases in both Ca2+ release from intracellular stores and Ca2+ influx through
      calcium channels.

PMID- 10069524
TI  - AMPA/kainate receptors permeable to divalent cations in amphibian central nervous
      system.
AB  - Glutamate receptors have been studied extensively in mammals but less explored in
      lower vertebrates. These receptors are present in amphibians. Using a recent
      method based upon agonist-induced cobalt uptake, we were able to detect the
      presence of functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)/kainate receptors permeable to divalent cations in tadpoles and in adults.
      The uptake specificity was checked by co-application of an antagonist. We studied
      the distribution of receptor-bearing cells in the principal brain regions. The
      distribution was similar in the two species studied: Rana esculenta (green frog)
      and Bufo bufo (common toad). The high number of cobalt-positive cells suggests
      that the AMPA/kainate receptors permeable to divalent cations play an important
      role in the anuran nervous system.

PMID- 10069525
TI  - Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin
      stimulated exocrine pancreatic secretion in humans.
AB  - Pancreatico-biliary secretion is reduced during acute hyperglycemia. We
      investigated whether alterations in pancreatico-biliary flow or volume output are
      responsible for the observed reduction in duodenal output of pancreatic enzymes
      and bilirubin during hyperglycemia. Eight healthy subjects were studied on two
      occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary
      output was measured by aspiration using a recovery marker under basal conditions
      (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin +
      CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate
      pancreatico-biliary flow and volume output. Secretin significantly (P<0.005
      P<0.05) increased volume and bicarbonate output and CCK significantly (P<0.01)
      increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume,
      both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin
      stimulated and secretin + CCK stimulated total pancreatico-biliary output were
      significantly (P<0.005-P<0.05) reduced compared to normoglycemia. The incremental
      outputs, however, were not significantly different between hyper- and
      normoglycemia. Pancreatic volume output was significantly (P<0.05) reduced during
      hyperglycemia compared to normoglycemia under basal conditions (31+/-16 m/h
      versus 132+/-33 m/h) during secretin infusion (130+/-17 ml/h versus 200+/-34 m/h)
      and during secretin + CCK infusion (370+/-39 ml/h versus 573+/-82 ml/h). Plasma
      PP levels were significantly (P<0.05) reduced during hyperglycemia. It is
      concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary
      output 2) the incremental pancreaticobiliary output in response to secretin or
      secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a
      reduction in volume output contributes to the inhibitory effect of hyperglycemia
      on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion
      suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and
      volume during hyperglycemia.

PMID- 10069526
TI  - Diet enriched with procyanidins enhances antioxidant activity and reduces
      myocardial post-ischaemic damage in rats.
AB  - Aim of this work was to study the efficacy of procyanidins from Vitis vinifera
      seeds, a standardized mixture of polyphenol antioxidants, on cardiac mechanics
      following ischemia/reperfusion stunning in the rat, after 3 weeks
      supplementation. Young and aged male rats were fed a diet enriched with
      procyanidins complexed (1:3 w/w) with soybean lecithin (2.4%); control animals
      (CTR-young and CTR-aged) received an equal amount of lecithin and 2 additional
      groups of animals the standard diet. At the end of the treatment, the total
      plasma antioxidant defense (TRAP), vitamin E, ascorbic acid and uric acid were
      determined in plasma and the hearts from all groups of animals subjected to
      moderate ischemia (flow reduction to 1 ml/min for 20 min) and reperfusion (15
      ml/min for 30 min). In both young and aged rats supplemented with procyanidins
      the recovery of left ventricular developed pressure (LVDP) at the end of
      reperfusion was 93% (p < 0.01) and 74% (p < 0.01) of the preischemic values and
      the values of coronary perfusion pressure (CPP) were maintained close to those of
      the preischemic period. Also creatine kinase (CK) outflow was restrained to
      baseline levels, while a 2-fold increase in prostacyclin (6-keto-PGF1alpha) in
      the perfusate from hearts of young and aged rats was elicited during both
      ischemia and reperfusion. In parallel, procyanidins significantly increased the
      total antioxidant plasma capacity (by 40% in young and by 30% in aged rats) and
      the plasma levels of ascorbic acid, while tend to reduce vitamin E levels; no
      significant differences were observed in uric acid levels. The results of this
      study demonstrate that procyanidins supplementation in the rat (young and aged)
      makes the heart less susceptible to ischemia/reperfusion damage and that this is
      positively associated to an increase in plasma antioxidant activity.

PMID- 10069527
TI  - CYP 3A proteins are expressed in human neutrophils and lymphocytes but are not
      induced by rifampicin.
AB  - Cytochrome P-450 3A (CYP 3A) enzymes, the prominent subfamily in the cytochrome
      system, are expressed in various extrahepatic tissues. Until now, their
      expression has been demonstrated in human polymorphic neutrophils (PMNs) but not
      in lymphocytes using immunohistochemistry and immunoblot analysis. Moreover,
      their potential modulation has not been determined yet. To study such an
      expression in different peripheral blood cell populations, rifampicin (600 mg/day
      during 6 days) was given to 8 healthy subjects. PMNs and lymphocytes were
      isolated by centrifugation of whole white blood cell fractions using Ficoll
      gradients before drug administration, immediately after, and 3 days after drug
      withdrawal. PMN and lymphocyte smears and homogenates were subjected to
      immunostaining and immunoblotting, respectively, with a mouse monoclonal antibody
      recognizing all CYP 3A proteins. These proteins were quantified by densitometric
      analysis. Before and after rifampicin administration, a positive cytoplasmic
      staining was observed in all PMNs and in about 50% of lymphocytes. CYP 3A
      expression in lymphocytes was further confirmed by positive immunoblots for
      lymphocyte homogenates. Neither in PMNs nor in lymphocytes, induction of CYP 3A
      protein expression was observed after rifampicin treatment despite overall
      induction of CYP 3A activity assessed by the urinary excretion of 6beta
      hydroxycortisol. These results demonstrate that CYP 3A proteins are
      constitutively expressed not only in PMNs but also in lymphocytes. However, in
      both cell lineages CYP 3A protein expression was not induced by rifampicin.

PMID- 10069528
TI  - Glucose-induced inhibition of angiogenesis in the rat sponge granuloma is
      prevented by aminoguanidine.
AB  - Angiogenesis and granulation tissue formation that occur following subcutaneous
      implantation of sponge implants in nondiabetic rats were inhibited by topical
      administration of D-glucose (22 mM). The healing impairment induced by glucose
      was analogous to healing failures associated with diabetes. Angiogenesis has been
      determined by measuring hemoglobin content in the implants, correlated with
      histological evidence of cellular infiltration and granulation tissue formation.
      The amount of hemoglobin detected in the glucose-treated implants was
      significantly lower (0.06+/-0.005 g/dl) than the amount in the controls that
      received glucose 5 mM (0.12+/-0.012 g/dl), saline (0.10+/-0.006 g/dl) or mannitol
      (0.086+/-0.007 g/dl). Parallel histological studies corroborated the biochemical
      findings. Daily intraperitoneal injection of aminoguanidine (AG, 50 mg/kg)
      prevented glucose-induced inhibition of neovascularization and cellular
      infiltration in the sponge granuloma. Our results show the direct inhibitory
      effect of high glucose in the development of granulation tissue and indicate that
      it may be associated with nonenzymatic glycation of key components of the healing
      process in the rat sponge granuloma.

PMID- 10069529
TI  - Selective stimulation of L-arginine uptake contributes to shear stress-induced
      formation of nitric oxide.
AB  - The aim of this study was to investigate the kinetics of L-arginine transport
      mechanisms and the role of extracellular L-arginine in nitric oxide formation
      during shear stress activation of endothelial cells. Porcine aortic endothelial
      cells were grown to confluence and were exposed to various amounts of shear
      stress for 40 min. Formation of nitric oxide was monitored by measuring elevation
      of endothelial cGMP. Activity of amino acid transport systems was determined by
      measuring the uptake of L-[3H]leucine (L system) and L-[3H]arginine (y+) under
      resting and shear stress condition. Shear stress-mediated nitric oxide formation
      critically depended on the presence of extracellular L-arginine, which increased
      shear stress-induced cGMP increases in a concentration dependent manner (EC50=123
      microM). In addition, shear stress increased L-arginine uptake, while the
      transport capacity for neutral amino acids (L system) remained unchanged under
      shear stress conditions. Analysis of the kinetics of the uptake of L-arginine
      under resting and shear stress conditions indicate that shear stress increased
      velocity of the high affinity, low capacity transport (y+) without affecting
      affinity of this system. These data suggest that shear stress selectively
      activates uptake of L-arginine in endothelial cells and that the uptake of L
      arginine might be important for shear stress-mediated nitric oxide formation.

PMID- 10069530
TI  - Dexamethasone inhibits leukocyte migration through endothelial cells towards
      smooth muscle cells.
AB  - Leukocyte interactions with endothelial cell monolayers (ECM) and smooth muscle
      cells (SMC) play an important role during inflammatory processes. Several studies
      describe an inhibitory effect of dexamethasone on polymorphonuclear leukocytes
      (PMNL), endothelial cell function, and interleukin-1 (IL-1) release. Aim of the
      current study was to investigate the influence of dexamethasone on leukocyte
      migration through an endothelial cell monolayer towards SMC-layers stimulated by
      tumor necrosis factor-alpha (TNF-alpha). Using a recently developed triple
      chamber migration system, SMC-layers were cultured on the bottom of a 24-well
      plate. On the upper surface of the first filter, ECM were cultured, the second
      filter was a collecting filter. The amount of leukocyte migration through ECM
      towards TNF-alpha-stimulated smooth muscle cell layers with and without
      dexamethasone-pretreatment was measured using a fluorescence technique. The
      pretreatment of SMC-layers with dexamethasone reduced the amount of leukocyte
      migration down to 92 +/- 8.8% (0.001 mM, p=n.s.), to 67 +/- 5.7% (0.01 mM,
      p<0.05), to 53 +/- 4.6% (0.1 mM, p<0.05), and to 41 +/- 5.0% (1 mM, p<0.05). In
      conclusion, dexamethasone treatment of smooth muscle cell layers inhibits
      leukocyte migration through ECM towards smooth muscle cell layers. The inhibition
      seems to be due to a decrease in IL-1 release. Treatment of all cell types, PMNL,
      endothelial cells, as well as smooth muscle cell layers, simulating an in-vivo
      situation, seems to have an additive effect.

PMID- 10069531
TI  - Membrane potential changes associated with calcium signals in human lymphocytes
      and rat mast cells.
AB  - Human lymphocytes and rat mast cells, two non-excitable cellular models, were
      used to investigate membrane potential changes accompanying Ca2+ signals. Cells
      were stimulated with agents known to induce both Ca2+ release from internal
      stores and influx of extracellular Ca2+, namely thapsigargin, ionomycin and
      compound 48/80. Thapsigargin and ionomycin were used to activate lymphocytes,
      while compound 48/80 was used to stimulate mast cells. Membrane potential changes
      and Ca2+ concentration were monitored with the fluorescent dyes bis-oxonol and
      fura-2, respectively. In lymphocytes, thapsigargin induced a hyperpolarization
      temporally correlated with the increase in intracellular Ca2+ concentration. This
      hyperpolarization is due to activation of a K+ conductance which consists of two
      phases, a first phase independent on external Ca2+ and a second one blocked in a
      Ca2+-free medium. Ionomycin induced a Ca2+-dependent depolarization attributed to
      a massive influx of external Ca2+. On the other hand, stimulation of mast cells
      with compound 48/80 produced a fast hyperpolarization and an increase in
      intracellular Ca2+ levels. Besides different time-courses, this hyperpolarization
      differs from that induced by thapsigargin in lymphocytes in two aspects, it is
      mainly due to a Cl(-)-entry current and exit of K+ and it is completely inhibited
      in the absence of extracellular Ca2+. Compound 48/80-induced histamine release is
      not related to membrane potential changes.

PMID- 10069532
TI  - High density of endothelin binding sites in the hearts of infants and children.
AB  - Endothelin (ET)-1 peripheral levels are high in children with respect to values
      of adults, but its pathophysiological significance remains to be established. In
      these conditions the interaction of ET-1 with its receptors may constitute a clue
      to the understanding of ET-1 function. Because a direct determination of ET
      binding sites in the heart of children is lacking, in this study we have
      attempted an assessment of the ET receptor status in cardiac tissue of infants
      (<1 year; 0.39 +/- 0.26 (SD) years, n=6) and children (1-14 years; 6.3 +/- 4.9
      years, n=7) as well as an evaluation of the receptor modulation as a function of
      age, associated to the observed decrease of plasma ET levels between infants and
      children. ET-1 binding sites have also been evaluated in atrium and ventricle
      membranes of adult subjects recipient of cardiac transplantation (CHF) and of
      post-mortem cardiac specimens (autopsy) of non cardiac patients. Considering all
      the pediatric patients (infants +/- children) studied, an affinity constant (Kd)
      value of 38.2 +/- 6.1 (SEM) pM and a density (Bmax) value of 166.2 +/- 11.6
      fmol/mg protein has been obtained for atrium. Similar values have been found in
      the ventricle. These values are significantly higher with respect to those
      obtained in adults: for atrial membranes, Kd = 22.2 +/- 9.7 and 11.6 +/- 1.8 pM;
      Bmax = 58.4 +/- 22.8 and 42.1 +/- 8.9 fmol/mg protein, respectively in explanted
      hearts and in post mortem specimens. No significant differences have been found
      in the binding parameters between infants and children, while, considering our
      results as a whole, a significant inverse correlation between Bmax and subject
      age (p<0.001) is suggested. The ET-A/ET-B ratio, evaluated by competition
      experiments with the specific ET-A antagonist BQ-123, was about 70:30 in
      pediatric patients, in both atrium and ventricle, without any difference between
      infants and children. Similar values for ET-A/ET-B ratio in adult CHF patients,
      in contrast to a reduction (significant only in ventricle) of the percent of ET-A
      subtype in autopsy, has been found. This is the first study concerning a direct
      evaluation of ET receptor status in children's hearts; the higher density of
      binding sites, associated to the elevation of plasma levels, could suggest a
      enhanced biological function of ET in children.

PMID- 10069533
TI  - Ischemia induces metallothionein III expression in neurons of rat brain.
AB  - Metallothionein III (MT-III) is a brain-specific member of the metallothionein
      family and binds zinc in vivo. In order to confirm the precise localization of MT
      III in normal rat brain and the change of MT-III expression after transient whole
      brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT
      III. Immunohistochemical analysis revealed that MT-III in normal brain is
      localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus,
      dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum.
      This expression pattern of MT-III was similar to that of MT-III mRNA observed by
      in situ hybridization studies. ELISA and Northern blot analysis revealed that MT
      III protein as well as mRNA levels were up-regulated in cerebrum soon after
      ischemic stress. Immunohistochemical analysis also demonstrated intense staining
      in neurons in injured brain after ischemia, which distributed in the same regions
      as in normal brain. These results suggest that MT-III plays an important role in
      protecting neurons from ischemic insult by reducing neurotoxic zinc levels and
      inhibits uncontrolled growth of neurites after ischemia.

PMID- 10069534
TI  - Muscarinic receptor occupancy by biperiden in living human brain.
AB  - Anticholinergic drug is often used to treat extrapyramidal symptoms. We measured
      muscarinic cholinergic receptor (mAchR) occupancy by the oral administration of
      biperiden in eight healthy subjects using positron emission tomography (PET) and
      [11C]N-methyl-4-piperidylbenzilate (NMPB). After the baseline scan each subject
      underwent one or two post-dose PET scans. mAchR occupancy was 10-45% in the
      frontal cortex three hours after the oral administration of 4 mg of biperiden.
      The occupancy correlated with the plasma concentration of biperiden in a
      curvilinear manner.

PMID- 10069535
TI  - Osteopontin (OPN) distribution in premalignant and malignant lesions of oral
      epithelium and expression in cell lines derived from squamous cell carcinoma of
      the oral cavity.
AB  - The objectives of this study were to assess the immunolocalization of human
      osteopontin (OPN) in oral lesions and to identify human cell lines of oral
      squamous cell carcinoma (OSCC) origin that express OPN mRNA. OPN was localized
      using immunohistochemistry in the following oral specimens: normal epithelium
      (n=6), epithelial hyperplasia (n=4), epithelial dysplasia (n=28), carcinoma in
      situ (n=11) and squamous cell carcinoma (n=43). Cell lines UMSCC-1, MDA TU 138,
      MDA 686LN, SCC4, SCC9, SCC25, CAL 27 and MDA 1483 were characterized for OPN mRNA
      expression using Northern blotting. OPN was not detected in normal oral
      epithelium. Intracellular and intercellular immunoreactivity was seen in 75% of
      hyperplasias, 57% of dysplasias, 54% of carcinoma in situ and 67% of squamous
      cell carcinomas. UMSCC-1 expressed high levels of OPN mRNA. We conclude that OPN
      protein is detectable in premalignant and malignant lesions arising from oral
      epithelium. UMSCC-1 may be a useful cell line in which to conduct in vitro
      studies designed to clarify the role of OPN in OSCC.

PMID- 10069536
TI  - DNA alterations in human oral squamous cell carcinomas detected by restriction
      landmark genomic scanning.
AB  - Genetic abnormalities in human oral squamous cell carcinomas (OSCC) were examined
      using restriction landmark genomic scanning (RLGS), a method of two-dimensional
      gel analysis allowing detection of amplifications and other aberrations in
      genomic DNA. DNAs from 11 oral tumours as well as from contiguous normal squamous
      epithelium, were cleaved with the restriction enzyme Not I, [32p] end-labeled and
      electrophoretically size-fractionated. Following a second digestion employing
      Hinf I, the further fragmented DNA was again electrophoretically separated. Five
      fragments/spots were found amplified in at least 64% (7/11) (chromosome nos. 4, 9
      12 or 22) of carcinomas, with one of these spots amplified in 100% (chromosome
      no. 4) of tumour samples. In addition, six other spots were frequently reduced in
      at least 55% (chromosome nos. 15 or 9-12) of tumour tissues. Further
      characterization of these common changes is needed to determine if they represent
      important alterations in OSCC.

PMID- 10069537
TI  - Expression of E-cadherin in oral cancer cell lines and its relationship to
      invasiveness in SCID mice in vivo.
AB  - We examined the expression of E-cadherin in nine oral cancer cell lines. HSC-4,
      NA, ZA, HOC927 and Ca9-22 cells strongly expressed E-cadherin [E-CD(++) cell
      line] and HSC-2 and HSC-3 cells weakly expressed E-cadherin [E-CD(+) cell line].
      All the cell lines that expressed E-cadherin were of cuboidal morphology and
      formed cobblestone colonies. In contrast, TSU and HOC313 cells had spindle
      shapes, formed dispersed colonies, and were completely negative for E-cadherin [E
      CD(-) cell line]. Moreover, all cell lines that expressed E-cadherin showed
      tumorgenicity in SCID mice, but E-CD(-) cell lines did not show tumorgenicity.
      The tumors derived from E-CD(+) cell lines invaded deeper into the connective
      tissues than those from E-CD(++) cell lines. In immunohistochemical analysis, the
      difference was more marked at the edges of the cancer nests. These results
      suggest that E-cadherin expression was relevant to the cell forms and the
      differential grade of cultured cells and that reduced E-cadherin in oral cancer
      may be associated with invasiveness in vivo.

PMID- 10069538
TI  - The in vitro post-antifungal effect of nystatin on Candida species of oral
      origin.
AB  - The post-antifungal effect (PAFE) is defined as the suppression of growth that
      persists following limited exposure of yeasts to antimycotics and subsequent
      removal of the drug. Although limited data are available on the PAFE of nystatin
      on oral isolates of C albicans, there is no information on non-albicans Candida
      species. As nystatin is the commonest antifungal agent prescribed in dentistry,
      the main aim of this investigation was to measure the PAFE of oral isolates of
      Candida belonging to six different species (five isolates each of C. albicans, C.
      tropicalis, C. krusei, C. parapsilosis, C. glabrata and C. guilliermondii)
      following limited exposure (1 h) to nystatin. The yeasts were examined for the
      presence of the PAFE after 1 h exposure to the minimum inhibitory concentration
      (MIC) of nystatin. The PAFE was determined as the difference in time (h) required
      for the growth of the drug-free control and the drug-exposed test cultures to
      increase to the 0.05 absorbance level following removal of the antifungal agent.
      The mean duration of nystatin-elicited PAFE was lowest for C. albicans (6.85 h)
      and greatest for C. parapsilosis (15.17 h), while C. krusei (11.58 h), C.
      tropicalis (12.73 h), C. glabrata (8.51 h), and C. guilliermondii (8.68 h)
      elicited intermediate values. These findings clarify another intriguing
      possibility for the persistent, chronic recurrence of oral C. albicans infections
      despite apparently adequate antifungal drug regimens. The significant variations
      in nystatin-induced PAFE amongst non-albicans species may also have clinical
      implications, in terms of nystatin regimens used in the management of these
      fungal infections.

PMID- 10069539
TI  - Immunocompetent cells in amalgam-associated oral lichenoid contact lesions.
AB  - Inflammatory cells in amalgam-associated, oral lichenoid contact lesions (OLL)
      were studied in 19 patients by immunocytochemistry using monoclonal antibodies.
      Ten of the patients displayed allergic patch test (PT) reactions to several
      mercury compounds and nine were negative. The immunocytochemical quantification
      showed a uniform composition of the inflammatory mononuclear cells in the two
      study groups. The number of HLA-D/DR-positive dendritic cells (P<0.001) and CD1a
      positive Langerhans cells (P=0.035) was significantly lower in the PT-negative
      than PT-positive patients. HLA-D/DR expression on keratinocytes varied from
      negative to full thickness staining of the epithelium. HLA-D/DR expression in the
      full thickness of epithelium (3) or through the basal and spinous cell layers (2)
      was seen in 5 of 8 PT-positive patients, whereas none of the PT-negative patients
      had this staining pattern (P=0.045). These patients also showed a good clinical
      response after amalgam removal. Consequently, OLL may represent a true delayed
      hypersensitivity reaction with a trans-epithelial route of entrance of the metal
      haptens released from dental restorative materials.

PMID- 10069540
TI  - Oral manifestations of HIV infection in a group of predominantly ethnic Chinese.
AB  - A total of 32 HIV-infected, predominantly ethnic Chinese individuals from Hong
      Kong were examined for oral mucosal lesions over a period of 1 year. The
      commonest oral lesion found was minor aphthous ulceration (27.4%), while
      xerostomia (17.8%), ulceration NOS (not otherwise specified; 12.3%), hairy
      leukoplakia (11.0%) and erythematous candidiasis (6.9%) were less frequent;
      Kaposi's sarcoma was notable for its absence. When the relationship between the
      number of oral lesions with age, risk group, medication taken, CDC staging and
      CD4+ count of the study group was investigated, a significantly higher number of
      oral lesions was associated with use of AZT, homosexuals and CDC stage IV; in
      contrast, a smaller number of lesions was found in those on antiparasitics and
      multivitamins (all P<0.05). When compared with studies from other parts of the
      world, the frequency of oral lesions appeared to be less common in the current
      study group. However, due to a lack of similar studies from the Asian region,
      especially in ethnic Chinese, it is not clear whether this difference could be
      attributed to racial, social or geographic factors.

PMID- 10069541
TI  - Bilirubin pigmentation of human teeth caused by hyperbilirubinemia.
AB  - This study was conducted to identify bilirubin in deciduous teeth obtained from
      two patients with a history of severe liver dysfunction. Teeth were
      histologically analyzed and bilirubin was extracted and quantified
      spectrophotometrically. Histological analysis revealed a green line in the
      dentine running parallel to the incremental lines. A chloroform/methanol/acetic
      acid (30:10:0.5, v/v) extract of the teeth was evaporated and the residue
      dissolved in chloroform. Absorption spectra were prepared before and after the
      diazo reaction. The absorption maximum shifted from 450 nm before to 540 nm after
      the diazo reaction and was higher than that of normal deciduous teeth. These
      results indicate that the discolouration of teeth in patients with severe liver
      dysfunction is due to bilirubin deposition.

PMID- 10069542
TI  - Immunohistochemical detection of DNA topoisomerase type II alpha and Ki-67 in
      adenoid cystic carcinoma and pleomorphic adenoma of the salivary gland.
AB  - Immunohistochemical detection of cell proliferation-associated antigens was
      investigated in 28 cases of adenoid cystic carcinoma (ACC) and 20 cases of
      pleomorphic adenoma (PA), using antibodies against DNA topoisomerase type II
      alpha (topo-II) (Ki-S1) and Ki-67 (MIB-1). The correlation of staining indices
      with clinicopathological data, histological features and prognosis was also
      studied. The topo-II value was significantly higher in ACC than in PA (P<0.0001),
      and highest in the solid growth pattern of ACC. In addition, significant
      relationships were found between topo-II values and clinical features such as
      local recurrence, surgical margins, and distant metastases. By log-rank test, the
      topo-II index was also correlated significantly with patient survival (P<0.01).
      The values of topo-II index paralleled those of Ki-67 index in ACC, and a
      correlation coefficient of 0.97 was obtained. Topo-II may be considered an
      additional marker for estimating the proliferating fraction of cells and for
      predicting the short-term prognosis for patients with salivary gland tumors.

PMID- 10069543
TI  - Oral wart associated with human papillomavirus type 2.
AB  - More than 100 human papillomavirus (HPV) types have been identified to date. Of
      these, 24 types have been described as being associated with oral lesions. HPV-2
      has been frequently associated with skin lesions, but the reports of oral lesions
      as features of mucosal infection are limited. A biopsy specimen of an oral wart
      on the right palate was taken from a 48-year-old man and examined for the
      presence of HPV The sections showed papillary growth of the epithelium with
      hyperkeratosis and parakeratosis, and koilocytotic changes of the cells located
      in the upper layers of the oral squamous cell epithelium. These histological
      features corresponded well to those of verruca vulgaris on the skin.
      Immunohistochemically, papillomavirus genus-specific capsid antigen was detected
      in most of the koilocytotic cells. In addition, Southern blot hybridization
      analysis revealed that the lesion harbored HPV-2 DNA. In situ hybridization with
      a biotinylated HPV-2 DNA probe clearly demonstrated viral DNA in the nuclei of
      squamous cells, which were located in a deeper layer of the epithelium than viral
      antigen-positive cells.

PMID- 10069544
TI  - Mixed-type liposarcoma of the oral cavity: a case with unusual features and a
      long survival.
AB  - A case of mixed-type liposarcoma, which showed unusual dedifferentiation in the
      recurrence, is reported. The rapidly growing mass in the palate of a 60-year-old
      Japanese woman first revealed a combination of myxoid liposarcoma with features
      resembling storiform malignant fibrous histiocytoma. The recurrent neoplasm,
      showing an abrupt transition between myxoid and non-lipogenic parts, partially
      reverted to sclerosing well-differentiated liposarcoma. The patient died 10.1
      years after the first operation.

PMID- 10069545
TI  - Effects of naltrexone on alcohol self-administration in heavy drinkers.
AB  - The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad
      libitum alcohol drinking in a bar/restaurant setting were investigated in heavy
      beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received
      50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized,
      double-blind crossover protocol. After 7 days of taking medication, subjects were
      provided with the opportunity to consume beer ad libitum during two, 90-min test
      sessions that were held 1 to 2 weeks apart. Blood samples were collected on test
      days to ensure medication compliance and to measure blood levels of NTX and the
      active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased
      urges to consume alcohol. NTX-treated subjects also took significantly longer to
      finish each glass of beer and were more likely to terminate beer drinking early.
      Self-report stimulation and ratings of positive mood states were lower during NTX
      treatment. Negative side effects of NTX, such as nausea and headache, were
      reported more frequently with NTX. Not all of the subjects decreased their beer
      intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not
      related to blood levels of the active metabolite beta-naltrexol or to a family
      history of alcoholism. Overall, the results of this study suggest that NTX
      affects a number of the components of alcohol drinking sequence, including
      lowering cravings, decreasing the positive reinforcing effects of alcohol, and
      increasing headache and nausea, each of which may contribute to reducing alcohol
      intake.

PMID- 10069546
TI  - Assessment of the role of kindling in the pathogenesis of alcohol withdrawal
      seizures and delirium tremens.
AB  - The aim of this study was to evaluate the hypothetical role of kindling
      phenomenon in the development and course of alcohol withdrawal (AW) seizures and
      delirium tremens (DT). The 2186 medical records of 1179 patients hospitalized in
      Nowowiejski Hospital in Warsaw from 1973 to 1987 were reviewed using a structured
      questionnaire. Investigating the role of kindling, a course of consecutive AW
      episodes of patients hospitalized several times was analyzed. The relationships
      of withdrawal seizures with the duration of alcohol abuse, the number of prior
      detoxification episodes, and other variables were also studied. Increasing
      severity of AW symptoms was observed during the course of consecutive episodes in
      22.5% of patients. The first episode of DT was preceded by withdrawal seizures in
      11% of cases. First-ever withdrawal seizures occurred more frequently in patients
      with head injury in the past and with coexisting symptoms of alcohol liver
      disease. Occurrence of withdrawal seizures and DTs did not correlate with the
      number of previous withdrawal episodes or with the length of period of intensive
      drinking. We concluded that the kindling model could be applied only to some
      cases in the development of AW seizures and DTs. Kindling should be considered as
      one of the multiple mechanisms involved in the pathogenesis of AW delirium.

PMID- 10069547
TI  - The role of somatic disorders and physical injury in the development and course
      of alcohol withdrawal delirium.
AB  - In a retrospective study, we evaluated the role of somatic disease and physical
      injury in the development and course of alcohol withdrawal delirium. Medical
      records of 1179 patients treated for alcohol withdrawal in Nowowiejski Hospital
      in Warsaw from 1973 to 1987 were reviewed using a structured questionnaire.
      Development, symptoms' severity, and the course of alcohol withdrawal delirium
      were assessed in possible relation to the somatic state of patients and other
      variables of alcohol dependence. Development of the first episode of delirium
      tremens (DT) was associated with the incidence of somatic disease or injury in
      19% of cases. Somatic disorders directly preceded the second episode of DT in 73%
      and the third in 57% of cases. A positive correlation was found between the
      greater severity and/or longer duration of DT symptoms, and occurrence of
      pneumonia, coronary heart disease, alcohol liver disease, and anemia, as well as
      daily amount of alcohol consumed during the last drinking bout. There was no
      relationship of severity of DT with the duration of alcohol abuse. Early
      development and severe course of alcohol withdrawal delirium correlated with the
      late beginning of excessive drinking (over the age of 40) and concomitant abuse
      of benzodiazepines or barbiturates. We concluded that somatic disorders or
      physical injury might trigger delirium during alcohol withdrawal, and have
      essential influence on the symptoms' severity and duration of DT. A more severe
      course of DT is also correlated with the quantity of alcohol consumed and
      concomitant abuse of sedatives.

PMID- 10069548
TI  - The effects of season and alcohol intake on mineral metabolism in men.
AB  - We have examined the relationship between self-reported alcohol intake (SRAI),
      season and mineral metabolism in a series of 96 men aged 32 to 78 years of age.
      Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated
      positively with liver function tests, including serum bilirubin, alkaline
      phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with
      serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone
      (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and
      pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the
      participants into two groups on the basis of their reported alcohol intake.
      Individuals with none-to-moderate intake had <8.4 oz/week of ethanol. Those with
      moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with
      none-to-moderate SRAI had a significant seasonal increase in iPTH, osteocalcin,
      urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25
      hydroxyvitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with
      moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have
      concluded that alcohol intake decreases seasonal change in serum iPTH. The
      biological effects of such alterations in parathyroid hormone levels include
      decreased seasonal loss of bone mineral density.

PMID- 10069549
TI  - The Oklahoma Postmenopausal Women's Health Study: recruitment and characteristics
      of American Indian, Asian, Black, Hispanic, and Caucasian women.
AB  - Since 1994, the National Institutes of Health has required the inclusion of women
      and minorities in all of its sponsored clinical research. This study describes a
      workable recruitment strategy that embraces the National Institutes of Health
      requirement. We describe the recruitment pattern of the Oklahoma Postmenopausal
      Women's Study conducted in the general community of Oklahoma City and in
      surrounding areas that are both urban and rural. For the period 1994 through
      1997, 491 postmenopausal women from all racial/ethnic groups in the community
      have participated in this study. Over 4 years of recruitment, the percentage of
      minority women in the study population has risen annually from 31% in 1994 to 81%
      in 1997. The overall percentage of minority women in the study population is
      currently 63.3%: American Indian, 21.8%; Asian, 3.7%; Black, 14.9%; Hispanic,
      9.4%; White/American Indian Blend, 13.6%; and White, 36.7%. The recruitment
      approach described may be implemented in a variety of research settings. Specific
      recruitment approaches are described, as well as the distribution of
      sociodemographic and health behaviors across and within ethnic/racial groups.

PMID- 10069550
TI  - Cognitive functioning moderates the relation between hyperactivity and drinking
      habits.
AB  - Previous research reveals an inconsistent link between hyperactivity and drinking
      (Weiss and Hechtman, 1993). This study sought to investigate whether cognitive
      functioning moderates the relation between these two variables. One hundred
      participants completed three measures of drinking habits, two measures of
      hyperactivity, and four measures of cognitive functioning. Confirmatory factor
      analysis showed that a three-factor model of hyperactivity, cognitive
      functioning, and drinking habits provided an excellent fit to the data. Stacked
      two-group analyses revealed that cognitive functioning moderated the association
      between hyperactivity and drinking habits. Drinking habits and hyperactivity
      correlated 0.408 (p < 0.05) for individuals low on cognitive performance; the
      correlation between these constructs was only 0.120 (NS) for individuals high on
      cognitive performance. Higher levels of cognitive functioning may buffer
      individuals from drinking alcohol in accordance with their hyperactive symptoms.

PMID- 10069551
TI  - Ritanserin in relapse prevention in abstinent alcoholics: results from a placebo
      controlled double-blind international multicenter trial. Ritanserin in Alcoholism
      Work Group.
AB  - Ritanserin, a long-acting specific 5-HT2 receptor antagonist, revealed promising
      effects on alcohol intake behavior in both animal and preliminary human studies.
      To test its effectiveness in alcohol dependence this phase III clinical trial was
      initiated. In a placebo-controlled, randomized, double-blind international
      multicenter study 493 patients with moderate or severe alcohol dependence (DSM
      III-R) were treated with three doses of ritanserin 2.5 mg/day (n = 122), 5 mg/day
      (n = 123), 10 mg/day (n = 126), or placebo (n = 122) over a period of 6 months.
      Ritanserin was well tolerated. The most frequent adverse experiences were
      headache and insomnia. A small increase in weight in the ritanserin-treated
      patients was observed. There were no significant differences between any dose of
      ritanserin and placebo in the relapse-rate, the time to relapse, craving for
      alcohol, or quantity and frequency of drinking after relapse. So far, neither
      ritanserin nor any other serotonergic medication has shown its specific
      effectiveness in relapse prevention in alcohol dependence.

PMID- 10069552
TI  - Innovations in adolescent substance abuse intervention.
AB  - Adolescent alcohol and other drug abuse is an important public health concern,
      and the past two decades has seen a dramatic increase in the demand for
      interventions to address substance use problems among teenagers. This demand has
      led to the development of multiple primary, secondary, and tertiary substance
      abuse prevention programs, some of which have little theoretical basis and most
      of which currently operate in the absence of data supporting their effectiveness.
      Very recently, there has been increased emphasis on the goal of developing and
      testing theoretically based and empirically supported intervention approaches for
      adolescent substance abuse. We describe five ongoing research programs devoted to
      meeting this goal. The background and rationale for each research program are
      discussed, and preliminary efficacy data concerning the specific interventions
      are presented.

PMID- 10069553
TI  - Effects of menstrual cycle and female sex steroids on ethanol pharmacokinetics.
AB  - This study investigated the influence of menstrual cycle and female sex steroid
      levels on ethanol pharmacokinetics. In a within-subjects design, 24 female
      volunteers each consumed 0.67 g x kg(-1) ethanol during the menstrual and luteal
      phases of their menstrual cycle. On each test day, we collected blood samples
      before ethanol administration to determine estradiol (E2) and progesterone (P)
      levels and to confirm ovulation. We took 20 or more postdrink breath ethanol
      concentration readings and examined pharmacokinetic differences between the two
      phases, using classical pharmacokinetic measures, as well as Michaelis-Menten
      measures. Despite highly significant differences in measured E2 as well as P
      levels on the 2 test days, and despite excluding subjects with anovulatory cycles
      from the analysis, there were no significant differences between menstrual and
      luteal phases for any of the pharmacokinetic variables. We found no correlation
      between E2 or P levels and any of the pharmacokinetic measures. In summary, we
      found no evidence that the tested menstrual cycle phases or varying E2 and
      progesterone levels significantly influence ethanol pharmacokinetics. Because
      previous studies about the topic have used few subjects and revealed
      controversial results, we consider our negative findings based on 24 subjects
      meaningful.

PMID- 10069554
TI  - Reduced EEG alpha power in the male and female offspring of alcoholics.
AB  - Abnormalities in resting EEG may be associated with a predisposition to
      alcoholism. Research also suggests that high levels of negative affect are
      important mediators of the predisposition to alcoholism in the offspring of
      alcoholics. This study tested the hypothesis that the offspring of alcoholics
      show deficits in EEG alpha and excessive EEG beta activity, which, in turn, would
      be associated with high levels of negative affect. Participants were 37 men and
      27 women with a positive family history of alcoholism and 37 men and 29 women
      with a negative family history of alcoholism. Personal and family history of
      psychopathology, psychological traits, and resting EEG were each assessed in
      separate testing sessions. Results indicated that subjects with a family history
      of alcoholism had reduced relative and absolute alpha power in occipital (O1, O2)
      and frontal (F3, F4, Fz) regions, and increased relative beta in both regions
      compared with subjects with a negative family history of alcoholism. EEG alpha
      and beta activity were not significantly correlated with trait anxiety, a
      diagnosis of depression, or antisocial traits. The results suggest that deficits
      in resting EEG alpha are associated with risk for alcoholism, although their
      etiological significance is unclear.

PMID- 10069555
TI  - Development of a composite measure for assessing alcohol treatment outcome:
      operationalization and validation.
AB  - This article operationally describes and empirically validates a composite
      outcome measure developed for use in a multisite alcohol treatment matching
      study. Using empirically based clinical guidelines to establish alcohol
      consumption and alcohol-related problems criteria, 1,726 subjects were classified
      as abstinent, moderate drinking without problems, heavy drinking or problems, or
      heavy drinking and problems at intake and 3, 6, 9, 12, and 15 months postintake.
      Subjects with poorer composite outcome also had poorer outcomes related to
      quantity and frequency of alcohol consumption, alcohol-related problems, serum
      gamma-glutamyltranspeptidase and other nonalcohol-related measures assessing
      psychiatric dysfunction, psychosocial functioning, and purpose or meaning in
      life. Differences in the present composite measure relative to other categorical
      measures used in research to date and the potential for incorporating nonalcohol
      specific variables into composite measures are discussed.

PMID- 10069556
TI  - Buspirone treatment of alcoholism: age of onset, and cerebrospinal fluid 5
      hydroxyindolacetic acid and homovanillic acid concentrations, but not medication
      treatment, predict return to drinking.
AB  - Disturbances in central nervous system serotonin (5-HT) have been implicated in
      the pathophysiology of alcoholism. To test the hypothesis that increasing 5-HT
      function could promote treatment compliance, we randomized patients who had
      completed a 5-week inpatient treatment program for alcoholism to receive either
      buspirone or placebo for 1 year. Ten of the 49 patients remained in the study for
      the entire year. The days to relapse did not differ significantly between
      patients receiving buspirone or placebo. Regardless of the medication, late-onset
      alcoholics had a longer time to relapse than early-onset alcoholics.
      Cerebrospinal fluid showed that patients with high concentrations of both the 5
      HT metabolite, 5-hydroxyindoleacetic acid, and the dopamine metabolite,
      homovanillic acid, were more likely to relapse, compared with patients with low
      concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic
      acid.

PMID- 10069557
TI  - Acetaldehyde enhances murine alpha2(I) collagen promoter activity by Ca2+
      independent protein kinase C activation in cultured rat hepatic stellate cells.
AB  - Protein kinase C (PKC) inhibitors decrease alpha1(I) collagen mRNA in stellate
      cells exposed to 200 micromol/liter of acetaldehyde. The purpose of these studies
      was to determine whether PKC activation plays a role in transcriptional
      activation of the alpha2(I) collagen gene. Cultured stellate cells were exposed
      to 200 micromol/liter of acetaldehyde. PKC, inositol triphosphate, diacylglycerol
      (DAG), and intracellular free calcium (Ca2+i) were measured. Alpha1(I) and
      alpha2(I) collagen messages were determined by reverse transcriptase-polymerase
      chain reaction. Activation of the alpha2(I) collagen promoter was determined in
      transiently transfected stellate cells. Acetaldehyde exposure enhanced PKC
      activity translocation to the particulate fraction at 20 min. Acetaldehyde did
      not increase Ca2+i, or inositol triphosphate but increased DAG levels at 20 min
      and 3 hr. Acetaldehyde increased both the alpha1(I) and alpha2(I) collagen
      messages in stellate cells. Calphostin C, a specific PKC inhibitor, which blocks
      DAG binding, eliminated both activation of the alpha2(I) collagen promoter by
      acetaldehyde and mRNA production by reverse transcriptase-polymerase chain
      reaction analysis. Similarly, D609, an inhibitor of DAG production, also
      inhibited alpha2(I) collagen gene expression. This study shows that collagen
      production by acetaldehyde is mediated by a calcium-independent PKC mechanism.

PMID- 10069558
TI  - Acute hemodynamic effects of ethanol in conscious spontaneously hypertensive and
      normotensive rats.
AB  - This study investigated the differential hemodynamic effects of small to high
      doses of ethanol in conscious age-matched spontaneously hypertensive rats (SHRs)
      and Wistar Kyoto rats (WKYs). Changes evoked by ethanol (0.25, 0.5, or 1 g/kg,
      i.v.) or equal volume of saline in mean arterial pressure (MAP), heart rate (HR),
      cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR)
      were followed for 90 min in the two rat strains. The baseline MAP (163 +/- 4 vs.
      113 +/- 2 mm Hg) of SHRs was significantly (p < 0.05) higher, compared with WKYs
      due mainly to the presence of an elevated TPR 13.82 +/- 0.12 vs. 2.51 +/- 0.09 mm
      Hg/ml/min/100 g, p < 0.05) in SHRs. In both rat strains, all doses of ethanol
      produced immediate increases in MAP at 1 min, after which the MAP responses
      varied and depended on the rat strain and dose of ethanol used. In WKYs, 0.25
      g/kg ethanol had no effect on MAP, but caused significant decreases in CO and SV
      and increased HR. Ethanol (0.5 and 1 g/kg) produced a short-lived (10 min) and
      dose-related increase in MAP. The higher dose (1 g/kg) of ethanol elicited
      significant (p < 0.05) increases in TPR that were counterbalanced by concomitant
      decreases in CO and SV. In SHRs, the two higher doses (0.5 and 1 g/kg) of ethanol
      elicited significant (p < 0.05) decreases and increases in MAP, respectively,
      compared with control (saline-treated) values. The pressor response to the 1 g/kg
      dose of ethanol was associated with an increase in TPR that achieved a
      statistical significance (p < 0.05) at 50 and 80 min after ethanol
      administration. HR was significantly (p < 0.05) reduced by the two higher doses
      of ethanol, whereas SV and CO were not changed. Blood ethanol concentrations
      measured 10, 30, and 60 min after ethanol administration were similar in SHRs and
      WKYs. These findings suggest that acute administration of ethanol to conscious
      rats elicits hemodynamic responses that are strain- and dose-dependent. In
      contrast to a short-lived and dose-related pressor response in WKYs, ethanol (0.5
      and 1 g/kg) elicited opposite and longer lasting effects on MAP (decreases and
      increases, respectively) in SHRs. In both rat strains, the pressor response to
      the higher dose of ethanol was associated with an increase in TPR; an effect that
      was compromised by a concomitant decrease in CO in WKYs but not SHRs.

PMID- 10069559
TI  - Effects of ethanol on the intraovarian insulin-like growth factor-1 system in the
      prepubertal rat.
AB  - Insulin-like growth factor-1 (IGF-1) is considered to play an important role
      during ovarian development and function. Because ethanol (ETOH) is a gonadal
      toxin in men, as well as male and female rats, we hypothesized that this drug may
      be having detrimental effects in the ovary by altering the intraovarian actions
      of IGF-1. In support of this notion, the present study was undertaken to examine
      the chronic effects of ETOH on the ovarian IGF-1 system in prepubertal female
      rats. Each rat was implanted with a gastric cannula on day 24 and began receiving
      either a control or ETOH liquid diet on day 29. The animals were killed on day
      34, confirmed to be in the late juvenile stage of development, and their ovaries
      and blood were collected. Using an RNase protection assay, we determined the
      expression of mRNAs encoding IGF-1 and the Type 1 IGF receptor in the ovaries of
      control and ETOH-treated rats. Results indicate that the ETOH-treated rats showed
      an increase in the ovarian expression of IGF-1a (p < 0.0001) and IGF-1b (p <
      0.001) mRNA, the two alternatively spliced forms of the IGF-1 gene. Conversely,
      ovarian IGF-1 protein levels were depressed (p < 0.05) in ETOH-treated rats as
      determined by radioimmunoassay. Furthermore, ETOH-treated rats showed a decrease
      (p < 0.01) in the expression of Type-1 IGF receptor mRNA with a subsequent
      decrease (p < 0.05) in the ovarian levels of IGF-1 receptor protein, as
      determined by Western blot analysis. Also, using Western immunoblotting, we
      determined increases in immunoreactive IGF-binding proteins-3 (p < 0.05) and 5 (p
      < 0.01), but not 4, in ETOH-treated rats as compared with controls. Furthermore,
      we observed a concomitant decrease (p < 0.01) in the serum levels of estradiol.
      These results demonstrate for the first time that chronic ETOH administration is
      capable of altering the prepubertal intraovarian IGF-1 signaling system. We
      suggest that, at least in part, these effects contribute to altered prepubertal
      ovarian function after chronic exposure to ETOH.

PMID- 10069560
TI  - Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses
      to chronic cold stress in rats.
AB  - Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary
      adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies
      that have investigated effects of prenatal ethanol exposure on HPA responses to
      acute or intermittent stressors, our study investigated HPA responses to a
      chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We
      tested the hypothesis that prenatal ethanol exposure would result in increased
      plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and
      increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in
      the paraventricular nucleus (PVN) of the hypothalamus compared to that in control
      animals. In addition, CORT and ACTH responses were measured after exposure to an
      acute stressor (i.p. isotonic saline injection), superimposed during chronic cold
      exposure, to examine possible sensitization of the HPA response to the acute
      stress. Thus, blood samples were collected at the end of each of the three
      periods of cold exposure, either before (0 min) or 15 min after acute stress. The
      subjects were adult male and female Sprague-Dawley rat offspring from prenatal
      ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups.
      Exposure to cold stress resulted in significant body weight loss in E males at 1
      day and in both males and females of all prenatal treatment groups by 3 days of
      cold stress. Males in all prenatal groups also exhibited significant increases in
      adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased
      CORT levels in E males and overall ACTH levels in E males and females compared to
      controls. ACTH levels were also higher overall in E compared to control males
      after acute stress (15 min condition). Sensitization of the CORT response to
      acute stress was observed in males but not females across all prenatal treatment
      groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN
      were not significantly affected by prenatal treatment or chronic cold stress in
      either males or females. In contrast, both males and females displayed increases
      in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These
      data support and extend previous work demonstrating differential effects of
      prenatal ethanol exposure on HPA responsiveness of male and female offspring, and
      suggest that E males may be more vulnerable to the effects of chronic cold stress
      than E females.

PMID- 10069561
TI  - Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty
      acids and alters essential fatty acid metabolism.
AB  - Rhesus monkeys that were maintained on an adequate diet but with low levels of
      essential fatty acids (1.4 en% linoleic, 18:2n-6, and 0.08 en%, linolenic acid,
      18:3n-3) became depleted of 20:4n-6, and 22: 6n-3 in their livers, plasma
      lipoproteins, and erythrocytes during an 18-month period of alcohol exposure (2.6
      g kg(-1) day(-1)). Monkeys that consumed alcohol also had higher plasma
      concentrations of 4-hydroxynonenal compared to controls. The metabolism of 18:2n
      6 and 18:3n-3 were evaluated in both groups of animals using deuterium-labeled
      substrates over a 9-day period. Alcohol consumption did not appear to have an
      effect on the absorption of either 2H5-18:2n-6 or 2H5-18:3n-3 ethyl esters into
      the circulation after a single oral dose. However, there was a greater enrichment
      of deuterium in the biosynthesized fatty acids, 20:4n-6 and 22:6n-3, in the
      plasma of the monkeys exposed to alcohol compared to controls. These results
      suggest that chronic alcohol exposure may lead to a stimulation of the rate at
      which long-chain polyunsaturated fatty acids are biosynthesized to compensate for
      an increase in lipid peroxidation.

PMID- 10069562
TI  - Effects of chronic ethanol ingestion on the vasoactive intestinal peptide
      receptor-effector system from rat seminal vesicle membranes.
AB  - We studied the modifications of the vasoactive intestinal peptide (VIP)
      receptor/effector system from the rat seminal vesicle after chronic ethanol
      ingestion. Ethanol treatment resulted in a decreased height of the secretory
      epithelium of seminal vesicle as well as in a weight loss of this gland. These
      morphological changes were accompanied by an increase of immunoreactive
      vasoactive intestinal peptide (VIP) levels and a decrease of the stimulatory
      effect of VIP adenylate cyclase activity in the seminal vesicle. The loss of
      sensitivity of the enzyme to VIP was conceivably related to a decrease in the
      affinity of VIP receptors rather than to a decrease in their number. The changes
      in the affinity of the VIP receptors were accompanied with a lower sensitivity of
      VIP binding to GTP, which suggest an uncoupling between the receptor and the
      transductor molecules. However, chronic exposure to ethanol did not modify either
      the levels of G-protein subunits (alpha(s) and alpha(i1/2)) or the GTPase
      activity from seminal vesicle membranes. Moreover, ethanol feeding did not affect
      adenylate cyclase activity stimulated by forskolin or by Gpp(NH)p. Thus, ethanol
      induced changes in the sensitivity of adenylate cyclase to VIP appear to be
      attributed to an alteration in the VIP-receptor/G-protein interphase rather than
      in the G-protein/adenylate cyclase connection.

PMID- 10069563
TI  - Osteopenia due to chronic alcohol consumption by young actively growing rats is
      not completely reversible.
AB  - Our project was conducted to determine if the deleterious effects of chronic
      alcohol consumption on growing bone are reversible if the adolescent stops
      drinking. Four-week old, female, Sprague-Dawley rats were housed and maintained
      in an AAALAC-accredited facility. Six animals each were placed on alcohol-fed
      (35% ethanol-derived calories), pair-fed or chow-fed diets for 2 or 4 weeks. A
      recovery group of six animals was alcohol-fed for 2 weeks followed by an
      additional 2 weeks of chow feeding. This group was pair-fed to an additional
      group of six animals that received liquid diet, pair fed to the recovery group
      for 2 weeks followed by 2 weeks on a pair-fed chow diet. Blood alcohol
      concentrations averaged 309 +/- 9 mg/dl. Morphological parameters of the femur,
      such as length, diameter, and volume were smaller in alcohol treated animals at
      both 2 and 4 weeks of feeding. Femur length and volume of recovery alcohol-fed
      animals were more than either 2- or 4-week alcohol-fed animals, but they were not
      as great as the same-age 4-week pair-fed or chow-fed animals. Diameter was
      similar to the 4-week alcohol-fed, but less than the chow-fed. Femur density was
      reduced at all time periods in the alcohol-fed animals. The recovery alcohol-fed
      animals had greater density than the 2-week alcohol, but not the 4-week alcohol
      fed animals. They did not, however, reach 4-week chow- or pair-fed levels. Tibia
      BV/TV was reduced in the 2- and 4-week alcohol- and pair-fed animals. BV/TV was
      greater in the recovery animals than either 2- or 4-week alcohols, but not as
      great as the chow-fed animals. At 2 weeks, calorie deprivation caused a reduction
      in insulin-like growth factor-1 (IGF-1) that was reduced even more by alcohol. By
      4 weeks, the calorie deprivation was no longer seen, but alcohol continued to
      reduce the values. Two weeks of alcohol followed by 2 weeks of chow diet returned
      the IGF-1 values to almost normal, but significantly different levels. The
      apparent improvement was probably due to continued growth of the young bones and
      not a regaining of bone lost during alcohol consumption.

PMID- 10069564
TI  - Effects of ethanol and ethanol withdrawal on nociception in rats.
AB  - The effect of acute and chronic administration of ethanol and ethanol withdrawal
      on a radiant heat tail-flick assay of nociception was examined in rats. Acute
      administration of ethanol (2.0 g/kg, i.p.) produced peak antinociception (68% of
      maximum) by 30 min, and effects were gone by 120 min. Cumulative doses of ethanol
      (0.5-2.0 g/kg, i.p.) produced dose-dependent increases in latencies to 49% of
      maximum. During chronic administration, a liquid diet containing ethanol (6.5%)
      was given for 10 days. Tail-flick latencies were measured on day 0 (baseline),
      day 2, 4, 6, 8, and 10 of chronic ethanol and at 3, 6, 12, and 36 hr after
      removal of ethanol. To test for behavioral tolerance, both between- and within
      group designs were used. In both between- and within-group experiments, the
      antinociceptive effects of chronic ethanol peaked by day 4 of exposure to the
      liquid diet, and tolerance developed by day 10. When the liquid diet was removed,
      hyperalgesia was detected at 6 and 12 hr after withdrawal, and was gone by 36 hr
      after withdrawal. When cumulative doses of ethanol (0.5-2.0 g/kg) were
      administered starting 12 hr after withdrawal, ethanol (0.5 g/kg) fully reversed
      the hyperalgesia induced by ethanol withdrawal, even though this dose was without
      antinociceptive effect in the absence of withdrawal. Higher doses of ethanol
      during ethanol withdrawal did not increase tail-flick latencies over baseline. In
      summary: (1) ethanol produces antinociception when administered acutely or
      chronically; (2) tolerance to the antinociceptive effects develops during chronic
      administration; (3) ethanol withdrawal induced hyperalgesia, which was reversed
      by ethanol; and (4) repeated testing did not produce behavioral tolerance.

PMID- 10069565
TI  - Chronic ethanol-initiated apoptosis in hepatocytes is induced by changes in
      membrane biogenesis and intracellular transport.
AB  - The outcome of chronic ethanol consumption recorded in liver by in situ staining
      of the genomic DNA in fragmented nuclei indicates the course of cellular events
      that has been coined as apoptosis or programmed cell death. Hence, we designed
      the study to determine which ethanol-induced modification of the cellular make-up
      is responsible for the hastening the cell damage. The in vitro assays were
      performed with cellular organelles and cytosol prepared from hepatocytes derived
      from rats subjected to 9 weeks of chronic alcohol consumption. The results were
      compared with the pair-fed controls receiving isocaloric liquid diet. In the
      initial phase of the studies, we established that the process of apoptosis was
      not triggered by the aberrant activity of neutral or acidic sphingomyelinase. The
      hepatocytes derived from alcohol and control diets manifested equal enzymatic
      activity. The de novo synthesis of sphingoid bases and ceramides in the alcohol
      derived sample of endoplasmic reticulum was reduced, but the in situ apoptosis
      was up to 36-fold higher than in the control. Also, the isolated hepatocytes
      contained a 2- to 4-fold higher amount of nucleosomal fragments in the cytosolic
      extracts. The endosomes from liver hepatocytes of ethanol-consuming rats, in the
      presence of the cytosol and mitochondria from pair-fed controls, disclosed 2 to 3
      times higher apoptotic potential than sample consisting of ethanol-derived
      fractions only, and 3 to 5 times higher than the control-derived fractions. The
      substantial increase in apoptosis, as recorded in the amount of DNA fragments
      released to the cytosol from the fresh nuclei, was also recorded when the
      microsomal membranes of endoplasmic reticulum and Golgi were incubated in the
      conditions with preserved intracellular transport. The maximal 20-fold increase
      of apoptotic activity was recorded in the incubation mixtures of ethanol-derived
      endoplasmic reticulum-Golgi membranes with control-derived cytosol in the
      presence of the ATP generating system. Results infer that the intracellular
      transport vesicles, generated from ethanol-modified membranes in the presence of
      the substrates that are available in the cytosol of the control hepatocytes,
      activate the apoptotic activity in the in vitro system. This interpretation is
      supported by the results of analysis of the clathrin-coated transport vesicles
      that, in contrast to nonclathrin transport vesicles, contain a sizable
      accumulation of ceramides that are known to induce apoptosis.

PMID- 10069566
TI  - A follow-up study on chromosomal aberrations in lymphocytes of alcoholics during
      early, medium, and long-term abstinence.
AB  - The frequencies of structural chromosomal aberrations were analyzed in peripheral
      blood lymphocytes of 31 chronic alcoholics at the beginning of an intensive
      outpatient treatment program at a neuropsychiatric clinic and were compared with
      31 controls matched for gender, age, smoking habits, and nondrinkers. A
      statistically significant difference was observed in the level of chromosomal
      aberrations in somatic cells from alcoholics when compared with controls (3.01%
      vs. 1.28%, p < or = 0.001). A follow-up study was carried out for a subset of the
      patients after 3 months (8 subjects) and 12 months (14 subjects) of controlled
      abstinence. A statistically significant increase in the mean frequency of cells
      with aberrations was observed in the group of 14 subjects reinvestigated after 12
      months of abstinence when compared with the mean value of the first blood samples
      immediately after hospitalization (4.61% vs. 3.01%; p < or = 0.001). An excessive
      increase in cigarette consumption during alcohol abstinence, reflected by a
      dramatic elevation of CO-hemoglobin levels, may, at least in part, account for
      this finding. In conclusion, chronic alcoholism leads to genotoxic effects that,
      instead of recovering after 1 year of alcohol abstinence, are even enhanced, most
      likely due to the "shift in addictive behavior."

PMID- 10069567
TI  - Modulation of caspase-3 activity and Fas ligand mRNA expression in rat liver
      cells in vivo by alcohol and lipopolysaccharide.
AB  - The purpose of this study was to determine if exacerbation of apoptosis precedes
      liver injury during chronic exposure of rats to alcohol. After 7 weeks of feeding
      an alcohol- or dextrin-containing liquid diet, the animals were treated with gram
      negative bacterial lipopolysaccharide (1 mg x kg(-1) body weight, intravenously)
      or sterile saline and sacrificed 3 hr after the treatment. Alanine:2-oxoglutarate
      aminotransferase (ALT) and lactate:NAD oxidoreductase [lactate dehydrogenase
      (LDH)] were measured in plasma. The caudate lobe of the liver was resected for
      histology, while the rest of the organ was perfused with collagenase to isolate
      hepatocytes, Kupffer cells (KCs), and sinusoidal endothelial cells (SECs) by
      centrifugal elutriation. Hepatocyte mitochondria were isolated by differential
      centrifugation of the cell homogenate. Reduced and oxidized glutathione (GSH and
      GSSG) in isolated hepatocytes and hepatocyte mitochondria, and malondialdehyde in
      hepatocytes were assayed. Caspase-3 activity and Fas ligand mRNA expression were
      determined in hepatocytes, KCs, and SECs. Plasma ALT and LDH activity, liver
      histology, GSH, GSSG and their ratio, and malondialdehyde content were not
      affected by alcohol treatment Caspase-3 activity was significantly increased in
      alcohol-treated rats in all three cell types, with the lowest response observed
      in hepatocytes and the highest in KCs. Fas ligand mRNA expression, which had the
      highest level in SECs, followed by KCs and hepatocytes, was not affected by
      alcohol administration. Lipopolysaccharide had the following effects: an increase
      in ALT in both pair- and alcohol-fed rats, and LDH only in alcohol-fed rats, a
      decrease in GSH + GSSG levels in both mitochondria and hepatocytes, an elevation
      of malondialdehyde content in hepatocytes, a raise in caspase-3 activity in all
      groups and cell types, and an augmentation of Fas ligand expression in
      hepatocytes and KCs, but not in SECs. These data suggest that, during chronic
      alcohol consumption, an exacerbated apoptosis precedes alcohol-induced liver
      injury.

PMID- 10069568
TI  - Effects of c-Src tyrosine kinase on ethanol sensitivity of recombinant NMDA
      receptors expressed in HEK 293 cells.
AB  - N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that are
      important mediators of the actions of the excitatory amino acid neurotransmitter
      glutamate. Previous studies have shown that ethanol inhibits the function of both
      wild-type receptors found in neurons and recombinant NMDA receptors expressed in
      heterologous cells, such as oocytes and transfected mammalian cells. Although
      some studies have reported that certain subunit combinations display an enhanced
      sensitivity to ethanol, this effect is not observed in all experimental systems.
      This discrepancy may be due to varying levels of endogenous modulators, such as
      kinases, between different cell preparations. In this study, we investigated the
      effects of tyrosine phosphorylation on the ethanol sensitivity of NMDA receptor
      function using a recombinant cell system where levels of both NMDA subunits and
      protein kinases can be more carefully controlled. Human embryonic kidney (HEK
      293) cells were transfected with different NMDA receptor subunits and a c-Src
      green fluorescent protein (GFP) fusion protein that could be directly visualized
      in living cells. Agonist-stimulated calcium flux was measured in single cells
      using fura-2 video imaging. As expected, cells transfected with the NR1/NR2B
      subunits were more sensitive to inhibition by the NR2 selective antagonist
      ifenprodil than those transfected with NR1/ NR2A or NR1/NR2A/NR2B subunits. All
      receptor combinations were inhibited by ethanol (25 and 100 mM), with the
      NR1/NR2B combination being slightly more sensitive than NR1/NR2A or
      NR1/NR2A/NR2B. Control and NMDA-receptor transfected HEK 293 cells displayed a
      low degree of tyrosine phosphorylation as measured by immunofluorescence and
      Western immunoblotting using an antiphosphotyrosine antibody. Phosphorylation was
      markedly enhanced in cells transfected with the c-Src-GFP fusion protein. The
      sensitivity of NMDA receptors to either 25 or 100 mM ethanol, or 10 microM
      ifenprodil, was not significantly altered by co-transfection with c-Src-GFP.
      These results indicate that, although NMDA receptors can be a target of c-Src
      tyrosine kinase, tyrosine phosphorylation by this enzyme does not modulate the
      inhibitory effects of ethanol on NMDA-activated currents.

PMID- 10069569
TI  - Chronic ethanol upregulates NMDA and AMPA, but not kainate receptor subunit
      proteins in rat primary cortical cultures.
AB  - The present study examined the effects of chronic ethanol exposure on the
      expression of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4
      isoxalone (AMPA) and kainate receptor subunit proteins in rat cortical neuronal
      cultures grown in media containing 2 mM (high) or 0.1 mM (low) glutamine.
      Immunoblot analysis of NMDA (NR1, NR2A, NR2B, and NR2D), AMPA (GluR1 and
      GluR2/3), and kainate (GluR6/7) subunit polypeptides in 3-, 5-, 8-, 10-, and 12
      day-old-cultures showed that NMDA receptor subunits NR1, NR2A, and NR2B and AMPA
      receptor subunits GluR2/3 progressively increased as a function of time, whereas
      levels of NMDA subunit NR2D were high at day 3 and progressively declined to
      barely detectable levels by day 12. Levels of AMPA subunit GluR1 and the kainate
      subunit GluR6/7 remained stable throughout the time course. Replacing the culture
      media with low glutamine media at culture day 5 did not alter the levels of
      subunit proteins measured at culture days 9 and 13. However, exposure of low
      glutamine cultures to 100 mM ethanol for 4 days (starting at culture day 9)
      significantly increased the levels of NMDA receptor subunits (NR1, NR2A, and
      NR2B) and AMPA receptor subunits (GluR1 and GluR2/3), but had no effect upon
      kainate receptor subunits (GluR6/7) or the synapse-associated proteins synapsin I
      and PSD-95. In contrast, chronic ethanol did not alter the levels of any of these
      subunit proteins in cells grown in high glutamine. These data demonstrate that
      under certain experimental conditions, prolonged exposure to ethanol upregulates
      NMDA and AMPA receptor subunit proteins, but has no effect upon kainate receptor
      subunit proteins. Because we have previously shown that acute ethanol can inhibit
      NMDA and AMPA, but not kainate, receptor function in these cultures, the increase
      in subunit expression likely reflects an adaptive response to the inhibitory
      effects of ethanol and suggests that both NMDA and AMPA receptors may play an
      important role in adaptation of the CNS to chronic ethanol.

PMID- 10069570
TI  - Upregulated expression of VLA proteins and CD29 in peripheral blood lymphocytes
      of chronic alcoholics without ethanol-related diseases.
AB  - To analyze adhesion molecule expression on peripheral blood mononuclear cells
      (PBMCs) and on different lymphocyte subpopulations (CD2+, CD8+, CD19+, and CD56+
      subsets) in chronic alcoholism, 30 well-nourished chronic alcoholics without
      ethanol-related diseases and 30 matched controls were included in the study.
      Adhesion molecules that mediate adhesion to other cells and to extracellular
      matrix proteins, and whose cellular expression is modified during lymphocyte
      activation, were selected for study. A detailed clinical evaluation, laboratory
      analysis, nutritional assessment, and study of adhesion molecule expression was
      performed. A significant higher expression of CD29 (beta1-integrin) (p = 0.001),
      VLA-3 (p = 0.002), VLA-4 (p = 0.03), and VLA-5 (p = 0.001) were observed on PBMCs
      of chronic alcoholics, compared with control subjects, whereas no changes were
      observed in CD18 (beta2-integrin) and CD50 (ICAM-3) expression. The upregulation
      of CD29 and VLA proteins only affected T lymphocytes (CD2+/CD8+/CD4+ cells).
      These data confirm that T cells of chronic alcoholics are basally activated and
      that changes in adhesion molecule expression on PBMCs may be responsible of
      disturbances of adhesion processes in chronic alcoholics without ethanol-related
      diseases.

PMID- 10069571
TI  - Chronic ethanol increases ganglioside sialidase activity in rat leukocytes,
      erythrocytes, and brain synaptosomes.
AB  - In view of the chronic alcohol-mediated pathological changes in various sialic
      acid-deficient glycoconjugates and the potential importance of sialidase in the
      generation of these glycoconjugates in the blood compartment and in the brain, we
      have investigated the effects of chronic ethanol feeding for 8 weeks on
      ganglioside sialidase activities in rat blood and brain. Ganglioside sialidase
      activity in erythrocytes (whether expressed as units/mg of protein or units/ml of
      blood) was 1.37- to 1.40-fold higher (p < 0.01) in the ethanol-fed group than in
      the control group. On the other hand, the same ethanol treatment increased
      sialidase activity in the leukocyte soluble fraction by 2.50- to 2.60-fold (p <
      0.01) and by 1.61- to 1.63-fold (p < 0.01) in the leukocyte particulate fraction,
      compared with the control group. More importantly, most of the blood compartment
      sialidase activity was localized in the leukocytes particulate fraction (80 to
      86% of total blood activity). Similarly, chronic ethanol treatment increased
      brain synaptosomal sialidase activity (whether expressed as units/gram of brain
      or units/mg of protein) 2.16- to 2.43-fold (p < 0.01). In contrast, brain
      lysosomal sialidase was not significantly altered by ethanol treatment, even
      though the major proportion of the brain sialidase activity was localized in the
      lysosomes. The proportion of synaptosomal sialidase activity as the percentage of
      total brain sialidase activity increased markedly from 13% in the control group
      to 24% in the ethanol group. Thus, chronic ethanol-mediated increases in
      sialidase activity in the leukocytes and brain synaptosomes could account for
      alterations in the ganglioside status of the animal and consequent adverse
      effects of chronic ethanol on behavioral and pathological changes.

PMID- 10069572
TI  - Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in
      murine and human bone marrow cultures.
AB  - Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a
      consequence of both systemic and direct cellular effects. To clarify some of the
      pathways by which alcohol exerts its actions directly on bone cells, we
      investigated the formation of early osteoblast progenitors (colony-forming units
      for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures
      exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone
      marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F
      formation (maximal reduction +/- SEM: 50 +/- 2%; p < 0.01) at concentrations
      ranging from 0.04% to 0.6% that are similar to those reached in vivo in
      alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of
      0.004% and 0.02%, and completely abolished it at the dose of 0.06%. Similarly,
      ethanol (at concentrations > or =0.02%) and acetaldehyde (from 0.004% to 0.06%)
      significantly decreased the number of CFU-F in human bone marrow cultures; the
      mean reduction observed with ethanol was 63 +/- 12% (p < 0.05), whereas
      acetaldehyde completely prevented CFU-F formation at the concentration of 0.06%.
      These in vitro observations were confirmed by the in vivo findings that the CFU-F
      formation in bone marrow cultures from nine young, chronic, noncirrhotic
      alcoholics was significantly reduced (70 +/- 15%), compared with seven age
      matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell
      proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas
      ethanol reduced proliferation only in MG-63 cells. Our results indicate that
      ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of
      the bone marrow, and this effect may contribute to the decreased bone formation
      observed in alcoholics.

PMID- 10069573
TI  - Batten disease: four genes and still counting.
AB  - The neuronal ceroid lipofuscinoses (NCLs, also known as Batten disease) are the
      most common childhood neurodegenerative disease. They are a group of inherited
      neurodegenerative disorders characterized by the accumulation of autofluorescent
      storage material in many cell types. Clinical features include seizures,
      psychomotor deterioration, and blindness, the ages and order of onset of which
      differ for each NCL type. An increasing number of subtypes caused by mutations in
      different genes are now recognized. With the advent of molecular genetics the
      basic genetic defect underlying each NCL phenotype is being determined, thus
      shedding light on the molecular basis of the NCLs and opening the way for the
      development of effective treatment. Four genes have been identified to date. The
      function of two of these is known and suggests that the primary defect in the
      NCLs lies in lysosomal proteolysis, the first example of this type of disease.
      However, since the function of the other two genes remains elusive, and at least
      four more genes remain to be identified, the molecular basis underlying the NCLs
      may be more complex than originally predicted.

PMID- 10069574
TI  - Disseminated corticolimbic neuronal degeneration induced in rat brain by MK-801:
      potential relevance to Alzheimer's disease.
AB  - Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors by MK-801 induces
      neuronal degeneration in the posterior cingulate/retrosplenial cortex and other
      corticolimbic regions although damage in the latter has not been adequately
      characterized. This disseminated corticolimbic damage is of interest since NMDA
      hypofunction, the mechanism that triggers this neurodegenerative syndrome, has
      been postulated to play a role in the pathophysiology of Alzheimer's disease
      (AD). Several histological methods, including electron microscopy, were used to
      evaluate the neurotoxic changes in various corticolimbic regions of rat brain
      following MK-801 or a combination of MK-801 plus pilocarpine. We found that MK
      801 triggers neuronal degeneration in a widespread pattern similar to that
      induced by phencyclidine and that females showed more damage than males. The
      neurotoxic reaction involved additional brain regions when muscarinic receptors
      were hyperactivated by administering pilocarpine with MK-801. Ultrastructural
      evaluation revealed that a major feature of the neurotoxic action involves
      degeneration of dendritic spines which entails loss of synaptic complexes. The
      ultrastructural appearance of degenerating neurons was generally inconsistent
      with an apoptotic mechanism, although evidence equivocally consistent with
      apoptosis was observed in some instances. The cell death process evolved
      relatively slowly and was still ongoing 7 days posttreatment. Relevance of these
      results to AD is discussed.

PMID- 10069575
TI  - Cloning of the presenilin 2 cDNA and its distribution in brain of the primate,
      Microcebus murinus: coexpression with betaAPP and Tau proteins.
AB  - A 1340-bp cDNA fragment encoding the lemurian presenilin 2 protein (PS2) was
      isolated from a Microcebus murinus brain cDNA library by PCR using
      oligonucleotide primers based on the nucleotide sequence of the human gene.
      Analysis of five isolated clones showed that the sequence encoded a 448-amino
      acid open reading frame, 95.5% identical to the human and 93.5% identical to the
      mouse presenilin 2 sequences. However, neither the localization of the 2
      positions in PS2 nor that of the 43 positions in PS1 associated with early onset
      Alzheimer's disease were changed. Expression of the presenilin 2 was detected by
      RT-PCR and compared with that of presenilin 1 and betaAPP in the brain and in
      peripheral tissues (liver, kidney, and spleen). Immunohistochemistry with a
      specific polyclonal antiserum raised against a synthetic peptide from the N
      terminal part of the human PS2 showed that the protein is distributed throughout
      the microcebe brain, in vascular and nerve structures. In cortical and in
      subcortical areas, PS2 labeling was weak and granular in appearance and was
      scattered throughout the cytoplasm of many neurones, extending into neurites. The
      gene expression of PS2 increased with age but was not affected by the presence of
      numerous amyloid plaques. Double labeling immunocytochemistry detected very few
      neurones with combined immunoreactivity PS2 and APP, or PS2 and Tau.

PMID- 10069576
TI  - Heterogeneous intracellular localization and expression of ataxin-3.
AB  - Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is an
      autosomal dominant neurodegenerative disorder caused by an unstable and expanded
      CAG trinucleotide repeat that leads to the expansion of a polyglutamine tract in
      a protein of unknown function, ataxin-3. We have generated and characterized a
      panel of monoclonal and polyclonal antibodies raised against ataxin-3 and used
      them to analyze its expression and localization. In Hela cells, multiple isoforms
      are expressed besides the major 55-kDa form. While the majority of ataxin-3 is
      cytosolic, both immunocytofluorescence and subcellular fractionation studies
      indicate the presence of ataxin-3, in particular, of some of the minor isoforms,
      in the nuclear and mitochodrial compartments. We also show that ataxin-3 can be
      phosphorylated. In the brain, only one ataxin-3 isoform containing the
      polyglutamine stretch was detected, and normal and mutated proteins were found
      equally expressed in all patient brain regions analyzed. In most neurons, ataxin
      3 had a cytoplasmic, dendritic, and axonal localization. Some neurons presented
      an additional nuclear localization. Ataxin-3 is widely expressed throughout the
      brain, with a variable intensity specific for subpopulations of neurons. Its
      expression is, however, not restricted to regions that show intranuclear
      inclusions and neurodegeneration in SCA3/MJD.

PMID- 10069577
TI  - Increased density of metallothionein I/II-immunopositive cortical glial cells in
      the early stages of Alzheimer's disease.
AB  - We have examined the possible role of metallothionein I/II (MT I/II) in
      Alzheimer's disease (AD), with a focus on the cellular localization of MT I/II
      relative to the astrocyte marker, glial fibrillary acidic protein (GFAP). In AD
      and preclinical AD cases, MT I/II immunolabeling was present in glial cells and
      did not show a spatial relationship with beta-amyloid plaques or neurofibrillary
      pathology. There was a six- to sevenfold increase in both MT I/II- and GFAP
      labeled cells in the gray matter of AD cases, relative to non-AD cases. However,
      there was a threefold increase in MT I/II-immunoreactive cells, but not GFAP
      labeled cells, in the gray matter of preclinical AD cases compared to non-AD
      cases. Therefore, the specific increase in MT I/II is associated with the initial
      stages of the disease process, perhaps due to oxidative stress or the
      mismetabolism of heavy metals.

PMID- 10069578
TI  - Differential regulation of the expression of nerve growth factor, brain-derived
      neurotrophic factor, and neurotrophin-3 after excitotoxicity in a rat model of
      Huntington's disease.
AB  - In the present study we have evaluated changes in nerve growth factor (NGF),
      brain-derived neurotrophic factor, and neurotrophin 3 (NT-3) mRNA expression
      induced by different glutamate receptor agonists injected into the neostriatum.
      Up-regulation of NGF expression was observed at 24 h after intrastriatal
      quinolinate injection, an N-methyl-D-aspartate receptor agonist, and this
      increase was maintained up to 7 days after lesion. NGF up-regulation was also
      apparent in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) treatment
      from 6 to 16 h postinjection. Instead, BDNF was up-regulated only at 6 h after
      kainate or AMPA excitotoxicity. Interestingly, NT-3 mRNA was down-regulated from
      10 to 16 h following AMPA lesion, while 1S,3R-1-aminocyclopentane-1,3
      dicarboxylic acid injection enhanced NT-3 mRNA levels at 10 h. Our results show a
      specific neurotrophin response induced by stimulation of each glutamate receptor.
      These activity-dependent changes might be involved in neuronal plasticity
      processes and may underlie the differential vulnerability of striatal neurons
      observed in neurodegenerative disorders.

PMID- 10069579
TI  - Beta-amyloid induces local neurite degeneration in cultured hippocampal neurons:
      evidence for neuritic apoptosis.
AB  - Many apoptotic insults, including beta-amyloid, cause neuritic degeneration. The
      possibility that apoptotic insults act directly on neurites was investigated in
      experiments using compartmented cultures of hippocampal neurons. Neurites in
      modified Campenot chambers displayed morphological signs of degeneration,
      including beading or blebbing, when exposed to beta-amyloid. At short time points
      neurite degeneration was limited to the distal portions of neurites directly
      exposed to beta-amyloid. Furthermore, annexin V binding detected extracellular
      exposure of phosphatidylserine in portions of neurites directly exposed to
      apoptotic insults. Pretreatment of the cultures with zVAD-fmk blocked annexin V
      binding induced by beta-amyloid and concanavalin A, suggesting that caspase
      activity was required. Caspase activation was also visualized in neurites locally
      exposed to apoptotic insults. Together these results show that apoptotic insults
      cause local neurite degeneration which displays morphological and biochemical
      characteristics of apoptosis and suggest that neurite degeneration may use
      mechanisms common to apoptosis.

PMID- 10069580
TI  - Boron neutron capture therapy of brain tumors: an emerging therapeutic modality.
AB  - Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs
      when boron-10, a stable isotope, is irradiated with low-energy thermal neutrons
      to yield alpha particles and recoiling lithium-7 nuclei. For BNCT to be
      successful, a large number of 10B atoms must be localized on or preferably within
      neoplastic cells, and a sufficient number of thermal neutrons must be absorbed by
      the 10B atoms to sustain a lethal 10B (n, alpha) lithium-7 reaction. There is a
      growing interest in using BNCT in combination with surgery to treat patients with
      high-grade gliomas and possibly metastatic brain tumors. The present review
      covers the biological and radiobiological considerations on which BNCT is based,
      boron-containing low- and high-molecular weight delivery agents, neutron sources,
      clinical studies, and future areas of research. Two boron compounds currently are
      being used clinically, sodium borocaptate and boronophenylalanine, and a number
      of new delivery agents are under investigation, including boronated porphyrins,
      nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies,
      liposomes, and epidermal growth factor. These are discussed, as is optimization
      of their delivery. Nuclear reactors currently are the only source of neutrons for
      BNCT, and the fission reaction within the core produces a mixture of lower energy
      thermal and epithermal neutrons, fast or high-energy neutrons, and gamma-rays.
      Although thermal neutron beams have been used clinically in Japan to treat
      patients with brain tumors and cutaneous melanomas, epithermal neutron beams now
      are being used in the United States and Europe because of their superior tissue
      penetrating properties. Currently, there are clinical trials in progress in the
      United States, Europe, and Japan using a combination of debulking surgery and
      then BNCT to treat patients with glioblastomas. The American and European studies
      are Phase I trials using boronophenylalanine and sodium borocaptate,
      respectively, as capture agents, and the Japanese trial is a Phase II study.
      Boron compound and neutron dose escalation studies are planned, and these could
      lead to Phase II and possibly to randomized Phase III clinical trials that should
      provide data regarding therapeutic efficacy.

PMID- 10069581
TI  - Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy
      for obsessive-compulsive disorder: relevance of the right hemisphere.
AB  - OBJECTIVES: Obsessive-compulsive disorder is a common mental disorder, notorious
      for its chronicity and intractability. Stereotactic lesions within the anterior
      limb of the internal capsule have been shown to provide symptomatic relief in
      such refractory cases, but only few systematic evaluations have correlated
      anatomic lesion location with individual postoperative outcome. PATIENTS AND
      METHODS: Between 1976 and 1989, extremely disabled and otherwise intractable
      patients with a chronic deteriorating clinical course of obsessive-compulsive
      disorder underwent bilateral thermocapsulotomy (n = 22) or radiosurgical gamma
      knife capsulotomy (n = 13) at the Karolinska Hospital, Stockholm. Clinical
      morbidity was monitored prospectively pre- and postoperatively by using
      standardized psychiatric rating scales. In 29 patients (thermocapsulotomy, n =
      19; gamma knife capsulotomy, n = 10), both psychiatric and magnetic resonance
      imaging follow-up data (median, 8.4 yr) were available. RESULTS: A right-sided
      anatomically defined lesion volume was identified in all successfully treated
      patients. This common topographic denominator was defined in the approximate
      middle of the anterior limb of the internal capsule on the plane parallel to the
      anterior commissure-posterior commissure line at the level of the foramen of
      Monro and 4 mm above on the plane defined by the internal cerebral vein. This
      region was unaffected in patients with poor outcomes. On the left side, no
      particular lesion topography was associated with clinical outcome. Topographic
      differences of lesion overlap between good and poor outcome groups were
      significant for the right side (Fisher's exact test, P < 0.005). CONCLUSION: The
      current anatomic long-term analysis after thermocapsulotomy or gamma knife
      capsulotomy for obsessive-compulsive disorder reveals common topographic features
      within the right-sided anterior limb of the internal capsule independent of
      treatment modality.

PMID- 10069582
TI  - Comparison of 1-year follow-up evaluations of patients with indication for
      pallidotomy who did not undergo surgery versus patients with Parkinson's disease
      who did undergo pallidotomy: a case control study.
AB  - Many reports published during the past 5 years have shown evidence of the
      beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients
      for up to 3 years, but none of them have compared patients who underwent surgery
      with a control group. OBJECTIVE: To compare the evolution of Parkinson's disease
      symptoms at 1-year follow-up between patients who underwent surgery and those who
      did not. MATERIAL AND METHODS: Ten patients with idiopathic Parkinson's disease
      refractory to treatment who were included in the Core Assessment for
      Intracerebral Transplantation program for PVP did not undergo surgery because
      financial support was lacking. These patients were followed up for 1 year as if
      they had been operated on and were finally compared with 10 patients having
      similar characteristics in whom PVP had been performed during the same period of
      time. RESULTS: There were no significant differences at basal evaluation in the
      motor section scores of the Unified Parkinson's Disease Rating Scale between
      those patients who underwent surgery and those who did not, but a significant
      reduction in Unified Parkinson's Disease Rating Scale motor score in the group
      who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias,
      which was nonsignificantly different at basal evaluation, showed, at the 1-year
      follow-up, a significant reduction in the group who underwent surgery (P < 0.04).
      Scores from the subsets of the Unified Parkinson's Disease Rating Scale
      addressing rigidity, tremor, and bradykinesia also proved significantly different
      at the 1-year follow-up. The slope of the line generated by the two evaluations
      for each group showed a negative value in the group who underwent surgery (value
      of -0.21) and a positive value in the group who did not (value of 0.148).
      CONCLUSION: At the 1-year follow-up, microelectrode-guided PVP produced
      significant changes in patient motor status and disease progression versus a
      comparable group of patients who did not undergo surgery during the same period
      of time.

PMID- 10069583
TI  - Postoperative neuroimaging of high-grade gliomas: comparison of transcranial
      sonography, magnetic resonance imaging, and computed tomography.
AB  - BACKGROUND: A precise and comprehensive knowledge of tumor burden and its extent
      and growth pattern in the pre- and postsurgical states is required to optimize
      tumor therapy and to determine treatment success and failure. This prospective
      study compares the diagnostic potential of computed tomography (CT), magnetic
      resonance imaging (MRI), and transcranial sonography (TCS) in the postoperative
      follow-up of brain tumors. METHOD: Twenty-six patients with high-grade gliomas
      were included in the study. After tumor debulking, a total of 31 biopsy specimens
      were obtained from the resection margin in 21 patients and histological findings
      were compared with the findings of early postoperative TCS, CT, and MRI. Findings
      indicating residual tumor tissue were nonlinear contrast enhancement at the
      resection site revealed by CT or MRI or hyperechogenic lesions revealed by TCS.
      Follow-up examinations using all three imaging techniques were performed every 3
      months. The end points of the follow-up were tumor recurrence as defined by CT
      and MRI, death, or severe clinical deterioration. RESULTS: On the basis of the
      above criteria, TCS identified residual tumor more often than did CT or MRI. In
      the group of 19 patients with histologically proven tumor remnants, residual
      tumor tissue was identified by TCS in all patients, whereas MRI and CT failed to
      show contrast enhancement in three and eight patients, respectively. However, the
      results of the TCS were false positive for one patient because of hemorrhage into
      the resection site. The average time to identification of tumor regrowth was 27
      weeks using TCS, 29 weeks using CT, and 33 weeks using MRI. Only the differences
      between TCS and MRI reached statistical significance. For one patient,
      multicentric tumor recurrence was not detected using TCS. CONCLUSION: TCS may
      complement CT and MRI in the postoperative follow-up of patients with high-grade
      gliomas. Because none of these modalities alone is both sensitive and specific,
      an integrated analysis of imaging findings is recommended.

PMID- 10069584
TI  - Embolization of rolandic cortex arteriovenous malformations.
AB  - OBJECTIVES: To evaluate the safety and efficacy of preradiosurgical and
      presurgical embolization of arteriovenous malformations (AVMs) involving the
      rolandic cortex. METHODS: Seventeen consecutive patients with rolandic AVMs seen
      during a 31-month period (December 1994-July 1997) were evaluated. All patients
      underwent superselective sodium amobarbital testing to determine any changes in
      the results of the neurological examinations before undergoing embolization. In
      16 of 17 patients (94.1%), somatosensory evoked potentials augmented physical
      examinations. Patients were embolized with N-butyl cyanoacrylate (Histoacryl; B.
      Braun, Melsungen, Germany) and iophendylate (Ethiodol; Savage Labs, Melville,
      NY). Rigid control of the mean arterial pressure (65-75 mm Hg) was maintained in
      all patients for 24 to 48 hours after embolization. RESULTS: Twenty-three
      embolization sessions were performed in 17 patients (mean, 1.5 sessions/patient),
      and a total of 40 feeding arteries were embolized. Two patients were unable to
      undergo embolization because of positive results of the amobarbital testing
      despite repeated attempts to reposition a microcatheter in the AVM circulation.
      In one case, somatosensory evoked potentials and the results of the physical
      examination were both positive; in the other case, only the somatosensory evoked
      potentials were used (in a pediatric patient under general anesthesia). All
      patients with AVMs that were embolized experienced a significant size reduction
      of their lesions (range, 20-95%; mean, 63%). There were no permanent
      complications. Four procedures (10% of the procedures, 23% of the patients)
      resulted in minor transient neurological deficits, with patients' conditions
      returning to baseline. Thirteen patients subsequently underwent radiosurgery,
      three underwent surgical resection, and one underwent combined surgery and
      radiosurgery. Complete obliteration of the lesions has been achieved in four
      patients to date (three who underwent surgery and one who underwent
      radiosurgery), with the remainder undergoing further follow-up. CONCLUSION: When
      properly evaluated before treatment, rolandic AVMs can be embolized with a high
      success rate (measured by completed embolization and size reduction) and a low
      complication rate.

PMID- 10069585
TI  - Extrinsic pathway of blood coagulation and thrombin in the cerebrospinal fluid
      after subarachnoid hemorrhage.
AB  - OBJECTIVE: The involvement of thrombin in the pathophysiology of subarachnoid
      hemorrhage (SAH) was investigated by comparing thrombin expression and extrinsic
      pathway activation in the cerebrospinal fluid (CSF) and blood of patients with
      SAH with the neurological grades, outcome, and presence of delayed cerebral
      vasospasm. METHODS: Blood and CSF samples were obtained from 38 patients with SAH
      on Days 3 through 5, 7 through 9, and 12 through 14 after the onset of SAH. CSF
      samples were also obtained from control patients. Thrombin-antithrombin III
      complex, prothrombin fragment F1 +2, tissue factor, and tissue factor pathway
      inhibitor were analyzed using enzyme-linked immunosorbent assay. RESULTS: No
      markers in the blood or CSF were correlated with neurological grades and outcome.
      Thrombin-antithrombin III complex and prothrombin fragment F1 +2 levels were
      significantly higher in the CSF of patients with SAH than in the blood or the CSF
      of control patients and were significantly higher in patients with vasospasm than
      in patients without vasospasm on Days 7 through 9. Tissue factor levels were
      significantly higher in the CSF of patients with SAH than in the blood, but the
      levels were close to those in the CSF of control patients. Tissue factor pathway
      inhibitor levels in the CSF of patients with SAH and control patients were under
      the detection limit. CONCLUSION: Thrombin in the blood may not reflect the
      pathophysiology of SAH. Imbalance between tissue factor and tissue factor pathway
      inhibitor in the CSF may tend to thrombin generation under normal physiological
      conditions and also after SAH. Thrombin in the CSF may be involved in the
      pathophysiology of vasospasm.

PMID- 10069586
TI  - Decompressive surgery for "pure" epidural hematomas: does neurosurgical expertise
      improve the outcome?
AB  - OBJECTIVE: The goal of this study was to determine whether patients with "pure"
      epidural hematomas can now be transferred safely to a neurosurgical unit for
      decompression or whether general or orthopedic surgeons must still be prepared to
      perform emergency craniotomies. METHODS: Between 1984 and 1996, 83 patients were
      surgically treated in our department for pure epidural hematomas, i.e., without
      associated intracranial lesions. The patient records were analyzed with respect
      to hematoma thickness, signs of herniation, delays from accident to
      decompression, results of any surgical attempts in local hospitals before
      admittance to our department, and clinical outcomes. RESULTS: The mortality rate
      was low (1 patient death, 1.2%). Seventy-nine patients (95%) experienced good or
      moderate outcomes (Glasgow Outcome Scale scores of 4 or 5). Twenty-four children
      all experienced good outcomes (Glasgow Outcome Scale scores of 5). The median
      delay from accident to decompression was 6.5 hours (mean, 7.1 h). When emergency
      surgery was attempted by general or orthopedic surgeons in local hospitals, the
      effective decompression was delayed (median, 4 h; mean, 12.5 h), and the final
      outcomes were considerably worse than for patients who were transferred without
      such surgical attempts. CONCLUSION: Patients with pure epidural hematomas have
      better prognoses than previously assumed. There is usually enough time to safely
      transfer patients to a neurosurgical unit, provided that transport is rapid and
      anesthesiological services are available during the transport. Surgeons without
      training in neurosurgery should not perform emergency craniotomies in local
      hospitals but, rather, should transfer patients as quickly as possible to the
      nearest department of neurosurgery.

PMID- 10069587
TI  - Chronic shunt-dependent hydrocephalus after early surgical and early endovascular
      treatment of ruptured intracranial aneurysms.
AB  - OBJECTIVE: The goal of this study was to document the influence of the treatment
      method (early surgery versus early endovascular treatment) on the development of
      chronic shunt-dependent hydrocephalus in a series of 242 patients treated within
      7 days after aneurysmal subarachnoid hemorrhage (SAH). METHODS: The following
      parameters were prospectively recorded in a computerized database and
      retrospectively analyzed for association with chronic shunt-dependent
      hydrocephalus: 1) Hunt and Hess grade, 2) Fisher computed tomographic grade, 3)
      incidence of repeat SAH, 4) aneurysm location, and 5) treatment method (early
      surgery versus early endovascular treatment). RESULTS: Forty of 187 patients
      (21.4%) who survived the SAH and its neurological and/or medical sequelae
      underwent definitive shunting for treatment of chronic hydrocephalus. The rate of
      shunt dependency was positively correlated with a higher Hunt and Hess grade (P <
      0.001), a higher Fisher computed tomographic grade (P = 0.003), the occurrence of
      intraventricular hemorrhage (P < 0.001), repeat SAH (P = 0.003), and aneurysms
      arising at the anterior communicating artery (P < 0.001). CONCLUSION: The results
      of the present study indicate that the treatment method used does not affect the
      risk of the later development of chronic shunt-dependent hydrocephalus (early
      surgery, 23.2% [29 of 125]; early endovascular treatment, 17.7% [11 of 62]; P =
      0.45).

PMID- 10069588
TI  - Subtemporal decompression: the treatment of noncompliant ventricle syndrome.
AB  - OBJECTIVE: To explore the effects of subtemporal decompression (STD) on the
      frequency of shunt revision and attendances with symptoms of raised intracranial
      pressure secondary to slit ventricle syndrome and slit ventricle-like syndrome. A
      renaming of these syndromes as noncompliant ventricle syndrome is suggested.
      METHOD: A retrospective review of the notes of all patients at our institution
      having STD from 1984 to 1997 was conducted. RESULTS: Twenty-eight patients
      underwent STD (age range, 4-31 yr). Thirty-two STD procedures were performed. The
      mean follow-up duration after STD was 5.3 years (range, 0-12 yr). The number of
      shunt revisions before STD was 128 (mean, 4.6 revisions; range, 0-30 revisions)
      and after STD was 28 (mean, 1.0 revision; range, 0-7 revisions). The number of
      attendances before STD was 213 (mean, 6.7 attendances; range, 1-31 attendances)
      and after STD was 57 (mean, 1.8 attendances; range, 0-10 attendances). Among 15
      patients for whom there was sufficient clinical data, 7 revisions were required
      during the 3 years before STD and 22 during the 3 years after STD. There were 53
      admissions during the 3 years before STD and 11 during the 3 years after STD.
      CONCLUSION: Although the overall incidence of shunt revision decreases, there is
      an early increase in the frequency of revision after STD. The number of
      admissions of patients with raised intracranial pressure symptoms reduces after
      STD, and we think that this is a more important factor in the consideration of
      this procedure than the number of recent revisions. We explore these arguments in
      this article.

PMID- 10069589
TI  - Ventral brain stem compression in pediatric and young adult patients with Chiari
      I malformations.
AB  - OBJECTIVE: The purposes of this study were as follows: 1) to determine the
      incidence and degree of ventral brain stem compression (VBSC) in pediatric and
      young adult patients with Chiari I malformations, and 2) to correlate VBSC with
      other imaging and clinical factors to help determine what amount of VBSC is
      successfully treated with a posterior decompressive procedure alone. METHODS: The
      magnetic resonance images and clinical histories of 40 pediatric and young adult
      patients with Chiari I malformations were analyzed for subjective grade of VBSC,
      distance of tonsillar descent, odontoid's relation to Chamberlain's and
      Wackenheim's line, clival length, foramen magnum diameter, syringomyelia,
      scoliosis, hydrocephalus, presenting clinical status, treatment, and outcome. To
      objectively measure the amount of ventral cervicomedullary encroachment by the
      odontoid and its investing tissues into the rostral spinal canal, a line (B-C2)
      was drawn between the basion and posteroinferior aspect of the C2 body on a
      sagittal magnetic resonance image. A line perpendicular to this line, pB-C2, was
      drawn through the odontoid tip to the ventral dura, and a distance (representing
      the amount of ventral canal encroachment) was measured. RESULTS: Flattening and
      distortion of the ventral brain stem were present in 48 and 28% of the patients,
      respectively. Only two patients had basilar invagination by traditional
      definitions. pB-C2 measurements correlated with the subjective grade of VBSC (P <
      0.05), age, and distance of tonsillar descent (P < 0.05). Eye motion
      abnormalities and upper cervical osseous anomalies were associated with higher pB
      C2 measurements. All patients with a pB-C2 measurement of less than 9 mm were
      treated successfully with posterior fossa decompression alone despite any
      subjective VBSC. Some patients with pB-C2 measurements greater than 9 mm had
      either preoperative neurological deficits or neurological worsening after
      posterior fossa decompression referable to VBSC. CONCLUSION: Patients with a pB
      C2 measurement of less than 9 mm do not require treatment directed at VBSC. In
      select patients with pB-C2 measurements of 9 mm or greater, reduction of VBSC may
      be prudent before posterior fossa decompression.

PMID- 10069590
TI  - Intracranial subdural empyemas in the era of computed tomography: a review of 699
      cases.
AB  - OBJECTIVE: Intracranial empyemas are the most common form of intracranial
      suppuration seen in our unit and, despite modern antibiotic therapy and advanced
      neurosurgical and imaging facilities, these pus collections remain a formidable
      challenge, often resulting in significant morbidity and death. We present an
      analysis of our 15-year experience with this condition in the era of computed
      tomography. METHODS: A retrospective analysis of 4623 patients admitted with
      intracranial sepsis during a 15-year period (1983-1997) identified 699 patients
      with intracranial subdural empyemas. The inpatient notes for these patients were
      analyzed with respect to clinical, radiological, bacteriological, surgical, and
      outcome data. Statistical analyses were performed. RESULTS: The 699 intracranial
      subdural empyemas accounted for 15% of all admissions for intracranial sepsis
      during the study period. Young male patients in the second or third decade of
      life were most commonly affected (62%), and the mean age was 14.65+/-12.2 years.
      Almost all patients (96%) underwent surgery. Eighty-two percent of patients
      experienced good outcomes (Glasgow Outcome Scale scores of 4 or 5). A morbidity
      rate of 25.9% (including postoperative seizures) was noted, and 85 patients died
      (mortality rate, 12.2%). CONCLUSION: Intracranial subdural empyema, which is a
      neurosurgical emergency, is rapidly fatal if not recognized early and managed
      promptly. Early surgical drainage, simultaneous eradication of the primary source
      of sepsis, and intravenous administration of high doses of appropriate antibiotic
      agents represent the mainstays of treatment.

PMID- 10069591
TI  - Partial labyrinthectomy petrous apicectomy approach to neoplastic and vascular
      lesions of the petroclival area.
AB  - OBJECTIVE: To study the value of an improvement of the presigmoid petrosal
      approach to the petroclival area by the addition of partial labyrinthectomy and
      petrous apicectomy and to document hearing and other results. METHODS: Thirty-six
      consecutive patients treated by this technique during a 2-year period were
      studied prospectively. The lesions treated included 33 petroclival neoplasms (25
      meningiomas, 5 chordomas, 1 chondrosarcoma, 1 trigeminal schwannoma, and 1
      epidermoid cyst) and 3 vertebrobasilar aneurysms. The patients underwent
      clinical, radiological, and neuro-otological examinations. RESULTS: There was no
      perioperative mortality. Cranial nerve deficits involving Cranial Nerves III, IV,
      V, and VI occurred in 17 patients (47%) postoperatively. Cerebrospinal fluid leak
      occurred in 12 patients (33%). Four of these patients were treated by lumbar
      drainage, two patients were treated by lumboperitoneal shunt, and six patients
      required reoperation and repacking of the middle ear. Hydrocephalus occurred in
      five patients (13.9%). There was one case of meningitis and another of systemic
      sepsis. All 36 patients underwent postoperative audiometric evaluation. When
      serviceable hearing was present preoperatively (Gardner-Robertson Grades I or
      II), it was determined to be preserved at postoperative follow-up in 81% of the
      patients (26 of 32 patients). CONCLUSION: The partial labyrinthectomy petrous
      apicectomy approach provided improved access to neoplasms of the clivus and
      petrous apex and the posterior cavernous sinus area and to vertebrobasilar
      aneurysms in the midclival area. This improvement in access permits more
      controlled and thorough treatment of these lesions, with reduced brain retraction
      and acceptable morbidity with respect to auditory function.

PMID- 10069592
TI  - Suprameatal extension of the retrosigmoid approach: microsurgical anatomy.
AB  - OBJECTIVE: This study was conducted to determine whether removing the bony
      prominence located above the porus of the internal acoustic meatus, called the
      suprameatal tubercle, and surrounding bone using the retrosigmoid approach would
      aid in the exposure of tumors that are located predominantly in the
      cerebellopontine angle but that also extend into the middle cranial fossa in the
      region of Meckel's cave and thus avoid the need for a supratentorial craniotomy.
      METHODS: Thirty cerebellopontine angles from 15 cadaveric heads examined using 3
      to 40x magnification provided the material for this study. A retrosigmoid
      craniotomy was completed and the exposure obtained before and after removing the
      suprameatal tubercle, and the surrounding bone was examined. In some cases,
      Meckel's cave and the tentorium lateral to the porus of Meckel's cave was opened
      to aid in the exposure. RESULTS: Removing the suprameatal tubercle and
      surrounding bone increased the exposure an average of 10.3 mm (range, 8.0-13.0
      mm) forward of the exposure, which could be obtained without suprameatal
      drilling. The extent of bone removal was limited on the lateral side by the
      posterior and superior semicircular canals and their common crus. CONCLUSION: The
      suprameatal extension of the retrosigmoid approach will permit removal of some
      tumors that are located mainly in the posterior fossa but that extend into the
      middle fossa in the region of Meckel's cave. The exposure can be increased by
      opening the superior petrosal sinus as it crosses in the upper margin of the
      porus of Meckel's cave and by opening the tentorium lateral to Meckel's cave.

PMID- 10069593
TI  - Microanatomy of the cerebellopontine angle and internal auditory canal: study
      with new magnetic resonance imaging technique using three-dimensional fast spin
      echo.
AB  - OBJECTIVE: We report a new magnetic resonance imaging technique that uses three
      dimensional fast spin echo and the minimum intensity projection method. Using
      this technique, detailed images of the cerebellopontine angle (CPA) and internal
      auditory canal (IAC) were obtained in normal volunteers and in patients with
      acoustic neuromas or hemifacial spasm. METHODS: Ten normal volunteers, 44
      patients with acoustic neuromas, and 31 patients with hemifacial spasm were
      studied using the three-dimensional fast spin echo magnetic resonance imaging
      protocol. The CPA and IAC were scanned by using a 1-mm slice thickness in the
      axial and parasagittal planes. RESULTS: Normal anatomy was as follows. 1) The
      vestibulocochlear nerve was ovoid near the brain stem and changed to a slightly
      crescentic configuration (C shape) as it traveled laterally. 2) Separation of the
      cochlear and vestibular nerves was observed near the central part of the IAC. 3)
      Discrimination between the superior and inferior vestibular nerves was also
      possible near the fundus of the IAC. 4) The facial nerve was easily identifiable
      as a discrete nerve at the anterior aspect of the vestibulocochlear nerve. 5) The
      meatal loop of the cerebellar artery was located medial to the porus in 44% of 95
      CPAs and reached the porus or protruded into the porus in 56%. Acoustic neuromas
      were as follows. 1) In a patient with a very small intracanalicular tumor, the
      nerve on which the tumor was located could be identified. 2) In 22 of 44 acoustic
      neuromas, cerebrospinal fluid was present between the tumor and the fundus of the
      IAC. Hemifacial spasm was as follows. The relationship between the responsible
      artery and the facial nerve could be precisely observed. CONCLUSION: The three
      dimensional fast spin echo method offers ultrahigh-resolution images, which are
      extremely useful in understanding the surgical anatomy of the CPA and IAC.

PMID- 10069594
TI  - Inhibition of phospholipase C-gamma1 activation blocks glioma cell motility and
      invasion of fetal rat brain aggregates.
AB  - OBJECTIVE: Phospholipase C (PLC)-gamma is a cytosolic enzyme activated by several
      growth factor (GF) receptors (epidermal GF receptor [EGFR], platelet-derived GF
      receptor, and insulin-like GF 1 receptor), and its activation is associated with
      increased cell motility (but not cell proliferation) in nonglioma cell lines.
      Because up-regulated activation of EGFR has been consistently linked to poor
      patient survival in patients with glioblastoma multiforme (GBM) and because
      inhibition of EGFR activation by tyrosine kinase inhibitors prevents glioma
      infiltration in vitro, we hypothesized that inhibition of PLC-gamma activation
      would inhibit glioma cell invasiveness. METHODS: Our experimental model assesses
      tumor spheroid invasion of fetal rat brain spheroids by confocal microscopy. We
      treated U87 GBM spheroids, and those derived from a single patient, with the PLC
      inhibitor U73122. We also transfected rat C6 glioma cells with the PLCz
      complementary deoxyribonucleic acid coding for a dominant negative PLC-gamma1 src
      homology-2/src-homology-3 peptide fragment, which blocks binding and activation
      of PLC-gamma1 by GF receptors. Two clones (C6F and C6E) were grown into spheroids
      and were tested for invasiveness in the spheroid model and for responsiveness to
      GFs in a standard in vitro motility assay. RESULTS: The infiltration rate of the
      patient GBM cell line overexpressing wild-type EGFR was reduced by 2 micromol/L
      U73122 from a slope (percent invasion/h) of 0.74+/-0.08 (with the inactive
      congener U73343) to 0.04+/-0.053 (P = 8 x 10(-7) by two-tailed t test, 92%
      reduction); the integral rate, another measure of invasion, was reduced from
      49.7+/-13 percent-hours per hour to 13.6+/-12 (P = 0.002, 72% reduction). The U87
      spheroid invasion rate was reduced by 0.5 micromol/L U73122 from 46.7+/-8.5
      percent-hours per hour to 11.2+/-4.6 (P = 3 x 10(-5)); the slope decreased from
      1.7+/-0.41 percent per hour to 0.35+/-0.14 (P = 0.0001). The C6F and C6E clones
      demonstrated attachment to and "surrounding" of the fetal rat brain aggregate but
      no true invasion by confocal or light microscopy. PLCz blocked the motility
      response to epidermal GF, platelet-derived GF, and insulin-like GF. There was a
      significant decrease in PLC-gamma1-associated tyrosine phosphorylation.
      CONCLUSION: These results support a key role for PLC-gamma activation as a common
      postreceptor pathway for GF-induced tumor infiltration and further identify PLC
      gamma1 as a possible target for anti-invasive therapy for GBMs.

PMID- 10069595
TI  - Adenovirus-mediated gene transfer of dominant negative Ha-Ras inhibits
      proliferation of primary meningioma cells.
AB  - OBJECTIVE: Previous studies demonstrated that activation of receptor tyrosine
      kinases in human meningiomas by an autocrine or paracrine growth-stimulatory loop
      plays an important role in meningioma proliferation. Although it is well
      established that the proliferative signal from protein tyrosine kinase receptors
      is transduced through Ras proteins, the relevance of the Ras pathway in
      meningioma proliferation, to our knowledge, has not been studied. The purpose of
      this study was, therefore, to determine whether Ras proteins are functionally
      important in meningioma proliferation. METHODS: Meningioma cells of nine primary
      cell cultures were infected with the recombinant adenovirus Ad-rasN17 encoding
      the dominant negative Ras protein or control adenovirus Ad-pAC. Ras-N17 is a Ras
      mutant protein with substitution of asparagine for serine at position 17 in the
      cellular Ha-Ras protein that inhibits function of all endogenous cellular Ras
      proteins. Proliferation of meningioma cells was measured using [3H]thymidine or 5
      bromo-2'-deoxyuridine labeling and detection assays. RESULTS: Infection of
      meningioma cells with Ad-rasN17 dramatically increased the expression levels of
      the Ras-N17 mutant protein and inhibited phosphorylation of the mitogen-activated
      protein kinases, compared with uninfected cells or cells infected with the
      control adenovirus. Suppression of Ras proteins inhibited proliferation of all
      exponentially growing and growth-arrested meningioma cells stimulated with serum.
      CONCLUSION: The obtained results suggest that proliferation of primary meningioma
      cells is dependent on the presence of functional Ras proteins. Therefore,
      inhibition of the Ras pathway may be important in preventing growth factor
      stimulated meningioma proliferation.

PMID- 10069596
TI  - Neurotrophic agents in fibrin glue mediate adult dorsal root regeneration into
      spinal cord.
AB  - OBJECTIVE: The aim of the present study was to determine whether neurotrophic
      factors (NTFs) exogenously administered in fibrin glue assisted cut dorsal root
      axons of adult rats to regenerate into the spinal cord. METHODS: Rats received
      intraspinal implants of fibrin glue containing neurotrophin-3, brain-derived NTF,
      ciliary NTF, or Dulbecco's modified Eagle's medium (control) into left dorsal
      quadrant cavities aspirated in the lumbar enlargement. The transected L5 dorsal
      root stump was placed at the bottom of the lesion cavity and was secured between
      the fibrin glue and the spinal cord. Regenerated dorsal root axons were
      subsequently labeled with immunohistochemical methods to demonstrate those that
      contained calcitonin gene-related peptide. RESULTS: Calcitonin gene-related
      peptide-immunoreactive dorsal root axons regenerated across the dorsal root
      spinal cord interface of rats with fibrin glue containing neurotrophin-3, brain
      derived NTF, or ciliary NTF, entered the spinal cord, and frequently arborized
      within clusters of motoneuronal cell bodies. Only a few axons regenerated into
      the spinal cord of animals with fibrin glue implants that lacked NTF, and their
      growth within the spinal cord was extremely limited. The results of quantitative
      studies confirmed these observations. CONCLUSION: Our results indicate that
      neurotrophin-3, brain-derived NTF, and ciliary NTF enhance dorsal root
      regeneration into spinal cord and that fibrin glue is an effective medium for
      intraspinal delivery of NTF. This method of delivering NTF may therefore provide
      a strategy for restoring injured spinal reflex arcs.

PMID- 10069597
TI  - Inhibition of peridural fibrosis after laminectomy using low-dose external beam
      radiation in a rat model.
AB  - OBJECTIVE: Clinical studies have revealed a significant association between the
      presence of extensive postlumbar discectomy peridural scar formation and the
      reoccurrence of low back and radicular pain. Low-dose perioperative radiation
      therapy has been shown to inhibit scar formation. Its effect on peridural
      fibrosis, however, has not been studied. METHODS: Thirty male Sprague-Dawley rats
      underwent L5 laminectomies. Ten rats each received a single fraction of 700-cGy
      external beam radiation to the lumbar spine 24 hours before surgery; 10 rats each
      received 700 cGy 24 hours after surgery. The remaining 10 rats served as a
      control group. All of the rats were killed 30 days after surgery. The spines were
      harvested, and axial histological sections through the laminectomy defect were
      evaluated. Each specimen was scored for extent, density, and arachnoidal
      involvement by fibrosis. RESULTS: There was a statistically significant
      difference between the treatment and control groups regarding the extent of
      fibrosis along the dura (P < 0.001), the density of fibroblasts (P < 0.005), and
      the arachnoid involvement (P < 0.01). There was no difference in fibrosis
      reduction between the groups receiving pre- and postlaminectomy radiation.
      CONCLUSION: Low-dose external beam radiation therapy administered before or after
      laminectomy in a rat model significantly decreases the extent, density, and
      arachnoidal involvement of peridural fibrosis. This technique may improve the
      outcome of patients who undergo reoperations for recurrent radicular and/or low
      back pain after successful lumbar discectomy in whom there is a significant
      amount of peridural fibrosis.

PMID- 10069598
TI  - Cerebrovascular Biology and the various neural barriers: challenges and future
      directions.
AB  - DESPITE MAJOR ADVANCES in neuroscience, potential therapeutic options for the
      treatment of central nervous system diseases often cannot be optimized secondary
      to the presence of the blood-brain barrier (BBB). During the next decade of
      inquiry, it is crucial that basic science and clinical research that is focused
      on overcoming the BBB, to optimize delivery to the central nervous system, be
      identified and supported as a priority topic. For this reason, the third
      international Cerebrovascular Biology and Blood-Brain Barrier Conference was
      convened in March 1998 in Gleneden Beach, OR. This meeting brought together basic
      science and clinical researchers from around the world to analyze BBB function
      and to discuss delivery of effective agents to the central nervous system for
      treatment of brain disease. This report summarizes the information presented at
      the meeting and the discussions that ensued. The current state of knowledge,
      obstacles to further understanding the BBB, and research priorities are
      identified.

PMID- 10069599
TI  - Sir Charles Ballance: pioneer British neurological surgeon.
AB  - Sir Charles A. Ballance (1856-1936) began his medical career at St. Thomas's
      Hospital the University College, London, England, in 1875, receiving honors in
      every subject and a gold medal in surgery. Victor Horsley (1857-1916) and
      Ballance were classmates at the University and in the later 1880s began work
      together at the Brown Institute and the National Hospital, Queen Square. In
      addition to important studies on vascular surgery, Ballance was involved in
      primate work on cerebral localization with lifelong friends Charles Beevor,
      Charles Sherrington, David Ferrier, and others. In June of 1887, Ballance
      assisted Horsley at Queen Square in the successful removal of an extramedullary
      spinal cord tumor. Horsley was about to abandon the operation, but his friend
      urged the removal of one lamina higher and the tumor was discovered. Ballance, a
      demonstrator in anatomy, realized the spinal cord segments lay higher in relation
      to the vertebral bodies than was generally appreciated. Ballance popularized the
      operation of radical mastoidectomy for advanced middle ear infection (1890),
      standardized an approach to drain or excise temporal brain abscesses, and was the
      first to clearly understand the neurological signs of cerebellar abscess (1894).
      Ballance also devised cranial base approaches to attack infectious
      thrombophlebitis of the lateral, petrosal, and cavernous sinuses. He was the
      first to completely remove an acoustic tumor (1894); 18 years later, the patient
      remained well. Ballance also drained a posterior fossa subdural hematoma (1906)
      and successfully sectioned the auditory nerve for Meniere's syndrome (1908).
      Ballance's operative experience with both supra- and infratentorial brain lesions
      included approximately 400 cases, which are detailed in his 1907 book, Some
      Points in the Surgery of the Brain and Its Membranes. His two-volume set, Essays
      on the Surgery of the Temporal Bone (1919), remains a brilliantly written and
      illustrated classic. Ballance was an expert on nerve regeneration and nerve
      grafting, and after many years of devoted research, he devised successful
      operations for facial nerve paralysis. For this and early vascular work, he is
      often credited as the first English surgeon to reintroduce classical Hunterian
      methods of experiment into surgery. He was honored as the founder and President
      of The Society of British Neurological Surgeons in 1926. Perhaps best known as a
      general and aural surgeon, Ballance was second only to Horsley in reputation as a
      pioneer British neurological surgeon. Described as a painstakingly slow but
      delicate and meticulous operator, Ballance made a contribution to neurosurgery
      and temporal bone surgery that was immense.

PMID- 10069600
TI  - Reactivation of herpes virus after surgery for epilepsy in a pediatric patient
      with mesial temporal sclerosis: case report.
AB  - OBJECTIVE: This case report is presented to raise the awareness of the potential
      risk of reactivation of herpes simplex virus (HSV) encephalitis after
      intracranial surgery. CLINICAL PRESENTATION: The case of an 8-year-old male
      patient who suffered a reactivation of HSV encephalitis after undergoing
      amygdalohippocampectomy for complex partial seizures is reported. This patient
      had previously contracted HSV 1 meningoencephalitis at the age of 16 months. Six
      years later, a left amygdalohippocampectomy was proposed after the development of
      intractable partial epilepsy associated with left mesial temporal lesions. During
      the postoperative period, the patient suffered severe clinical deterioration with
      partial status epilepticus, aphasia, and hyperthermia, which resolved after
      intensive antiepileptic treatment supported by acyclovir. CONCLUSION: We advise
      prophylactic pre-, peri-, and postoperative treatment with acyclovir for patients
      with known histories of HSV encephalitis who undergo intracranial procedures.

PMID- 10069601
TI  - Long-term remission of malignant brain tumors after intracranial infection: a
      report of four cases.
AB  - OBJECTIVE: This report describes four patients with malignant brain tumors in
      whom regression or cure seems to be related to infection with bacteria. METHODS:
      An analysis of the four clinical cases reported and a review of the literature
      produced a comprehensive body of both experimental and clinical data concerning
      the antineoplastic properties of bacteria. RESULTS: Although direct oncolytic
      effects from bacteria have been suggested, immune adjuvant responses to tumor
      suppression are emphasized. In one of our patients, infiltration of numerous
      granulocytes and lymphocytes into the tumor at the time of initial surgery was
      observed, suggesting that a spontaneous immune reaction had begun. Also, in two
      other patients, tumor aggression occurred in association with a bacterial process
      that was not in direct contact with the tumor. In three of the cases described,
      Enterobacter aerogenes was recovered from the microbial cultures. Whether the
      presence of this organism was coincidental or whether this organism plays an
      important role in tumor defense is not known; however, a specific cross-reactive
      immunological attack to the tumor is suggested. CONCLUSION: The case histories
      presented in conjunction with the relevant literature reviewed support the
      concept that microbial infections may influence immune responses in brain tumor
      defense.

PMID- 10069602
TI  - Immature teratoma originating from the pituitary gland: case report.
AB  - OBJECTIVE AND IMPORTANCE: Recently, it has been suggested that the primary site
      of suprasellar germinomas is the neurohypophysis, but nongerminomatous germ cell
      tumors originating from the pituitary gland have been rarely reported. CLINICAL
      PRESENTATION: A 27-year-old man presented with panhypopituitarism, bitemporal
      hemianopsia, and mild right oculomotor nerve paralysis. Diabetes insipidus was
      not observed. The tumor was shown by magnetic resonance imaging to extend and
      invade bilateral cavernous sinuses, sellar and clival dura mater, and the
      sphenoid sinus mucosa. INTERVENTION: Transsphenoidal removal yielded a diagnosis
      of immature teratoma. Serum alpha-fetoprotein was prominently elevated. Magnetic
      resonance imaging and surgical findings of the superiorly displaced residual
      pituitary gland strongly suggest the pituitary origin of this rare tumor.
      CONCLUSION: In contrast to the neurohypophyseal germinomas, nongerminomatous
      malignant germ cell tumors originating from the pituitary gland tend not to be
      associated with diabetes insipidus and thus mimic adenomas. Evaluation of the
      tumor markers is necessary in young patients with cavernous sinus syndrome and
      invasive pituitary tumors with heterogeneous intensity revealed by magnetic
      resonance imaging.

PMID- 10069603
TI  - Intraventricular cavernomas: three cases and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Cavernomas occur very rarely in the ventricular system.
      We report three cases of intraventricular cavernomas and review the literature.
      CLINICAL PRESENTATION: A 16-year-old female patient presented with a sudden
      distal deficit of the left superior limb. She had a voluminous tumor involving
      the two lateral ventricles, with radiological evidence of recent hemorrhage. A 30
      year-old man presented with generalized seizures and a right hemiplegia related
      to a 4-cm-diameter cavernoma in the two lateral ventricles involving the
      interhemispheric scissure through the corpus callosum and left centrum ovale. The
      radiological appearance was not typical and did not allow the diagnosis. A 42
      year-old man had a cavernoma in the third ventricle, which was responsible for
      his short-term memory loss. This cavernoma had been revealed by computed
      tomography that was performed after intracerebral hemorrhage related to another
      cavernoma in the right parietal lobe occurred. INTERVENTION: Stereotactic
      biopsies allowed the diagnosis of intraventricular cavernoma in the first case.
      Surgical removal via a right transcortical transventricular approach and a
      transcallosal approach in the first and second cases, respectively, was complete,
      resulting in good outcomes. Surgical removal via a right transcortical
      transventricular approach in the third case was partial. CONCLUSION:
      Intraventricular cavernomas are so uncommon that only 42 well-documented cases
      have been previously reported in the literature. It seems that their radiological
      diagnosis may be difficult because of their uncommon location in the ventricular
      system and their voluminous size. A wrong preoperative diagnosis has sometimes
      been the cause of inefficient therapy, such as radiotherapy, for these surgically
      curable benign lesions.

PMID- 10069604
TI  - Anterior approach to intramedullary hemangioblastoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intramedullary spinal cord tumors are generally
      operated on by using the posterior approach. However, the posterior approach may
      not be suitable for a tumor in the anterior part of the spinal cord. In this
      report, we describe a case of a cervical intramedullary tumor that was
      successfully removed by using the anterior approach. CLINICAL PRESENTATION: A 48
      year-old woman presented with lower cranial nerve disturbance and motor weakness
      of the upper extremities. Magnetic resonance imaging revealed a large extensive
      syrinx and an intramedullary enhanced tumor at the C6 level. The tumor was
      located at the left of the anterior part of the spinal cord. INTERVENTION: Based
      on these findings, the anterior approach was used in performing a corpectomy of
      C5 and C6. The tumor was highly vascular and was resected without resulting in
      any operative deficits. The pathological diagnosis was hemangioblastoma.
      CONCLUSION: The present case suggests that the anterior approach is an important
      option among surgical approaches to the intramedullary tumor in cases in which
      the tumors are small in size and are located in the anterior part of the cervical
      cord.

PMID- 10069605
TI  - An unusual case of the complete Currarino triad: case report, discussion of the
      literature and the embryogenic implications.
AB  - OBJECTIVE AND IMPORTANCE: We present and illustrate an unusual case of the
      complete familial Currarino triad (an association between a bony sacral defect, a
      presacral mass, and an anorectal malformation) in which the teratoma arose from
      the conus medullaris and contained mature neurons, glia, and branching ependymal
      canals that were in communication with a terminal syrinx. The embryogenic
      implications are discussed. CLINICAL PRESENTATION: The patient was a term neonate
      when discovered to have imperforate anus. Further workup revealed lumbosacral
      dysraphism with a presacral mass, a rectovaginal fistula, and a single pelvic
      kidney. The family pedigree revealed a familial transmission pattern; the patient
      had a second cousin with anal atresia and a first cousin with similar sacral
      anomalies. The motor level was L4 with trace L5, and there was absent sensation
      in the sacral dermatomes. INTERVENTION: A diverting colostomy was performed on
      Day 14, and the infant returned at 3 months of age to undergo near-total
      resection through the previous abdominal approach. Only a subtotal resection was
      possible because the mass arose from the low-lying conus and was firmly adherent
      to the sacral nerve roots and iliac vessel. Follow-up magnetic resonance imaging
      performed 18 months after surgery revealed that the residual tumor had not
      progressed. CONCLUSION: Complete Currarino triad is rare and is familial in half
      of the cases. The special features of the tumor in our case were the presence of
      mature neurons with ependymal canals and its origin from the conus. The possible
      embryogenesis may provide evidence that the caudal notochord is important for
      organized secondary neurulation.

PMID- 10069606
TI  - Endovascular treatment of hemifacial spasm associated with a cerebral
      arteriovenous malformation using transvenous embolization: case report.
AB  - OBJECTIVE AND IMPORTANCE: To illustrate that decompression of the facial nerve by
      transvenous endovascular treatment may relieve hemifacial spasm (HFS) caused by
      dilated veins. CLINICAL PRESENTATION: A 35-year-old man suffered severe chronic
      right HFS associated with a dilated right lateral mesencephalic vein lying in the
      vicinity of the facial nerve. This nonessential vein was recruited as a secondary
      collateral drainage from an inoperable left temporo-occipital arteriovenous
      malformation. INTERVENTION: The lateral mesencephalic vein was reached through
      the superior petrosal sinus using a transfemoral venous approach and was occluded
      with interlocking detachable coils (Target Therapeutics, Freemont, CA). There was
      complete remission of HFS without recurrence after 2.5 years of follow-up.
      CONCLUSION: This case report supports vascular compression in the pathogenesis of
      HFS and suggests that facial nerve injury is not essential for the therapeutic
      effect of surgical decompression.

PMID- 10069607
TI  - Endovascular stenting of an acutely thrombosed basilar artery: technical case
      report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: The goal of this report was to describe the successful
      percutaneous endovascular use of a Gianturco-Roubin-2 coronary stent in the
      treatment of an acute atherothrombotic occlusion of the basilar artery. To our
      knowledge, the percutaneous endovascular deployment of an intra-arterial stent
      for the treatment of an acute atherothrombotic occlusion of the basilar artery
      and the percutaneous endovascular placement of a Gianturco-Roubin-2 stent in the
      basilar artery have not been previously reported. CLINICAL PRESENTATION: An 83
      year-old man presented with a recurrent, transient, locked-in syndrome resulting
      from a lower basilar artery occlusion caused by vertebrobasilar thrombosis
      superimposed on severe proximal basilar artery atheromatous stenosis.
      INTERVENTION: After successful superselective intra-arterial thrombolysis of the
      vertebrobasilar clot, balloon angioplasty of the underlying basilar artery
      stenosis was performed, without significant angiographic improvement.
      Percutaneous endovascular deployment of a Gianturco-Roubin-2 coronary stent of 4
      mm diameter was subsequently performed, with excellent angiographic results.
      CONCLUSION: The patient made a very good neurological recovery but unfortunately
      died as a result of cardiogenic shock and sepsis. Detailed neuropathological
      follow-up results are presented; stent patency was revealed in the postmortem
      examination. The anatomic and pathophysiological considerations of basilar artery
      stent placement for the treatment of acute basilar artery occlusion related to
      atherosclerotic stenosis are discussed.

PMID- 10069608
TI  - The use of Gore-Tex membrane for adhesion prevention in tethered spinal cord
      surgery: technical case reports.
AB  - OBJECTIVE: The incidence of retethering caused by postoperative adhesions at the
      repair site after initial tethered spinal cord surgery is not uncommon. To assess
      the effectiveness of a Gore-Tex membrane in preventing these adhesions, only
      clinical radiological and experimental animal evaluation has been reported. In
      this report, we describe two cases in which Gore-Tex membrane was implanted at
      the initial untethering surgery and in which we were able to confirm the real
      effectiveness of the Gore-Tex membrane during a second operation. METHODS: In the
      first patient, Gore-Tex membrane was used for dural repair in the untethering
      surgery of the split spinal cord malformation. Because of the suspicion of a
      thickened filum terminale, repeated surgery was indicated 10 months after the
      initial procedure. In the second patient, Gore-Tex membrane was implanted during
      the initial untethering surgery for a lipomyeloschisis and a dermal sinus.
      Because of a persistent fistula of the dermal sinus, a second operation was
      necessary 1 year after the first operation. RESULTS: During the repeated surgery,
      a thorough inspection of the implanted Gore-Tex membrane revealed no adhesions
      between the Gore-Tex membrane and the intradural content in both cases.
      CONCLUSION: We support the use of Gore-Tex membrane in the prevention of
      postoperative dural adhesions in the repair of spinal dysraphism.

PMID- 10069609
TI  - Postcontrast magnetic resonance imaging to predict progression of traumatic
      epidural and subdural hematomas in the acute stage.

PMID- 10069610
TI  - Hypothermic circulatory arrest in neurovascular surgery: evolving indications and
      predictors of patient outcome.

PMID- 10069611
TI  - Library: historical perspective.

PMID- 10069612
TI  - Posterior C1-C2 transarticular screw fixation for atlantoaxial arthrodesis.

PMID- 10069613
TI  - Spinal cord compression by catheter granulomas in high-dose intrathecal morphine
      therapy: case report.

PMID- 10069614
TI  - Microvascular decompression of the left lateral medulla oblongata for severe
      refractory neurogenic hypertension.

PMID- 10069615
TI  - Arithmetical abilities in Alzheimer disease.
AB  - The purpose of this research was to analyze the calculation abilities in
      Alzheimer Disease (AD). Twenty right-handed patients meeting the DSM-IV (American
      Psychiatric Association, 1994) criteria for AD were studied. Age ranged from 64-
      to 88-year-old. A neuropsychological test battery including language, memory,
      constructional abilities, attention, mathematics, and abstraction tests was
      administered. In addition, the Mini-Mental State Exam (MMSE) (Folstein, Folstein,
      McHugh, 1975) was also administered. Mathematical subtests correlated higher than
      the MMSE with the scores in the different neuropsychological tests. Highest
      correlations of the mathematical subtests were observed with language repetition,
      non-verbal memory, and attention tasks. It is proposed that mathematical ability
      tests represent in AD an excellent predictor of general intellectual performance.
      It is further proposed that disturbances in arithmetical ability should be
      included as a diagnostic criteria for AD.

PMID- 10069616
TI  - Experimental induction of intermale aggressive behavior in limbic epileptic rats
      by weak, complex magnetic fields: implications for geomagnetic activity and the
      modern habitat?
AB  - In three separate experiments, groups (4/group) of male rats with limbic epilepsy
      were exposed for 80 min every 24 hr during the midscotophase for 24 successive
      days to sham-field conditions or to one of four complex patterns of magnetic
      fields whose average intensities ranged between 20 nT to 500 nT. The numbers of
      episodes of boxing, biting, mounting, eating, drinking and grooming were then
      recorded each night during the latter 20 min. Moderately strong statistically
      significant interactions occurred between the presence or absence of the field
      and the pattern of the field explained 25% and 50% of the variance in the numbers
      of biting and boxing responses, respectively. Other behaviors were not affected.
      The results suggest that group aggression can be increased or decreased as a
      function of the temporal characteristics and morphology (shape) of the applied
      magnetic field.

PMID- 10069617
TI  - MMPI-2 characteristics of adults diagnosed with attention deficit disorder.
AB  - Attention Deficit Disorder (ADD) has been increasingly recognized as extending
      into adulthood, affecting occupational, interpersonal, and psychological
      functioning. The Minnesota Multiphasic Personality Inventory (MMPI) and its
      revision (MMPI-2) have been widely used in the assessment of patients with
      psychiatric disorders, but few studies have attempted to characterize the
      personality profiles of individuals with ADD and none have used the MMPI-2.
      Thirty-three patients with ADD and 33 schizophrenia patients were compared to 46
      healthy control subjects on the MMPI-2 validity, clinical and Harris-Lingoes
      scales. With the exception of significantly lower scores for general affective
      distress (F), thought disorder (Sc), and paranoia (Pa), ADD subjects demonstrated
      remarkably similar profiles to those seen in the schizophrenia group. Significant
      differences between the three groups were found on a majority of the clinical
      scales, with ADD subjects showing similar profile elevations as schizophrenic
      subjects on both clinical- and sub-scales. These results were consistent with
      previous research using the original MMPI in adults with ADD, and confirm that
      examination of MMPI-2 profiles may be a useful diagnostic aid for this disorder.

PMID- 10069618
TI  - Executive dysfunctions in children with attention deficit hyperactivity disorder.
AB  - One hundred and twenty-four male children ranging in age from seven to 12 years
      old were selected. The sample was divided into two groups: (1) sixty-two with
      attention deficit hyperactivity disorder (ADHD) children; and (2) sixty-two
      normal matched controls (N-ADHD). Three tests were individually administered: (1)
      Wisconsin Card Sorting Test (WCST); (2) Verbal fluency and semantics (animals and
      fruits); and, (3) Picture Arrangement subtest of the WISC-R. For all the test
      scores, statistically significant differences were found between both ADHD and N
      ADHD groups. Two separate factor analyses were performed, using the normal and
      ADHD groups. Four factors were found for the N-ADHD group, which accounted for
      85.7% of the variance. The factor structure presented some similarities in both
      groups: Factor 2, 3 and 4 in the control group corresponded to factors 1, 2 and 3
      in the ADHD group. Nonetheless, in the ADHD group Factor 1 (Abstraction and
      Flexibility Factor) was absent. Results are interpreted as supporting the
      hypothesis of executive dysfunction in children with ADHD.

PMID- 10069619
TI  - Intersession interval affects performance in the Morris Water Maze.
AB  - We have recently reported an effect that shows a sexually dimorphic difference in
      cognitive style rather than ability. The preparation for potentially producing
      this proximal perceptual style effect is one where rats are first given 4-trial
      daily acquisition sessions for 12 days with the platform always in the same
      position, but sometimes visible (perceptual, "look-out" condition) and sometimes
      hidden (conceptual, "navigational" condition). On the first, probe trial of the
      13th day, the platform's position is shifted to a point very close (proximal) to
      the rat's starting position, and made visible. The proximal perceptual style
      (PPS) effect has emerged sexually dimorphically in that only females swam
      straight to the newly positioned proximal platform. Other studies have shown that
      the PPS effect is eliminated (with females behaving like males) by nicotine and
      prepubertal ovariectomy, and does not occur in prepubertal females. Also, as no
      sex-related effects emerged during acquisition during these studies, the PPS
      effect appears to be a function of cognitive style rather than ability. The
      present study varied age, and, in an effort to economize on time, shortened
      acquisition to 6 days by having morning and afternoon sessions each day. To our
      surprise, this relatively subtle psychological manipulation eliminated the PPS
      effect, and also yielded some sex- and age-related effects during acquisition: A
      male advantage was observed and prepubertal rats had longer escape latencies;
      there was no significant interaction between sex and age.

PMID- 10069620
TI  - Attentional stimuli and programming hand selection: a developmental perspective.
AB  - This experiment examined the use of attentional stimuli for reaching in hemispace
      by strong right-dominant adults and children. Driving the hypothesis was the
      notion that developmental factors associated with use of attentional information
      may affect the programming of reaching movements in hemispace. Although the
      general pattern of responses was similar for both samples, children did not use
      attentional cues to program reaching movements in contralateral hemispace as
      effectively as adults. This result suggests that motor dominance and perhaps
      other factors were pivotal in motor programming for children. One possible
      explanation for the general behavior observed underlies an attentional
      hemispheric bias for a tendency to use the hand that is on the same side as the
      stimulus.

PMID- 10069621
TI  - Aromatherapy positively affects mood, EEG patterns of alertness and math
      computations.
AB  - EEG activity, alertness, and mood were assessed in 40 adults given 3 minutes of
      aromatherapy using two aromas, lavender (considered a relaxing odor) or rosemary
      (considered a stimulating odor). Participants were also given simple math
      computations before and after the therapy. The lavender group showed increased
      beta power, suggesting increased drowsiness, they had less depressed mood (POMS)
      and reported feeling more relaxed and performed the math computations faster and
      more accurately following aromatherapy. The rosemary group, on the other hand,
      showed decreased frontal alpha and beta power, suggesting increased alertness.
      They also had lower state anxiety scores, reported feeling more relaxed and alert
      and they were only faster, not more accurate, at completing the math computations
      after the aromatherapy session.

PMID- 10069622
TI  - Neuropsychological testing in adult attention deficit hyperactivity disorder: a
      pilot study.
AB  - Diagnosing adult ADHD is frequently problematic because behavioral information
      from the patient's childhood, and multiple informants who can delineate the
      patient's current behavior, are often unavailable. This preliminary study was
      designed to explore whether objective neuropsychological testing may be a useful
      adjunct in the diagnosis of adult ADHD. Nineteen adults diagnosed with ADHD
      according to DSM-IV criteria, along with 10 controls, were assessed using a
      neuropsychological battery which comprised tests assessing linguistic, visual
      spatial perceptual, academic, attentional and inhibitory control, mnestic and
      executive functions. Following preliminary analyses, designed to determine which
      variables best discriminated the groups, receiver operating characteristic (ROC)
      curves were constructed to determine the sensitivity and specificity of the best
      measures both alone and in combination. Only three measures significantly (p <
      0.01) distinguished the groups; Digits Backwards from the WAIS-R and two reaction
      time measures from a computerized task modeled after Luria's Competing Motor
      Programs. ROC curve analyses indicated that in combination these measures had
      greater than 90% accuracy for classifying ADHD and non-ADHD patients. While
      further research is necessary these preliminary findings suggest that
      neuropsychological testing may be a useful adjunct in the differential diagnosis
      of adult ADHD.

PMID- 10069623
TI  - Correlation of applied kinesiology muscle testing findings with serum
      immunoglobulin levels for food allergies.
AB  - The pilot study attempted to determine whether subjective muscle testing employed
      by Applied Kinesiology practitioners, prospectively determine those individuals
      with specific hyperallergenic responses. Seventeen subjects were found positive
      on Applied Kinesiology (A.K.) muscle testing screening procedures indicating food
      hypersensitivity (allergy) reactions. Each subject showed muscle weakening
      (inhibition) reactions to oral provocative testing of one or two foods for a
      total of 21 positive food reactions. Tests for a hypersensitivity reaction of the
      serum were performed using both a radio-allergosorbent test (RAST) and immune
      complex test for IgE and IgG against all 21 of the foods that tested positive
      with A.K. muscle screening procedures. These serum tests confirmed 19 of the 21
      food allergies (90.5%) suspected based on the applied kinesiology screening
      procedures. This pilot study offers a basis to examine further a means by which
      to predict the clinical utility of a given substance for a given patient, based
      on the patterns of neuromuscular response elicited from the patient, representing
      a conceptual expansion of the standard neurological examination process.

PMID- 10069624
TI  - Functional recovery and vitamin E level following sciatic nerve crush injury in
      normal and diabetic rats.
AB  - Extensive biochemical data document the involvement of oxygen derived free
      radicals (ODFR) in recovery following neurotrauma as well as diabetic neuropathy.
      Vitamin E is considered as one of the principle protective mechanism against
      oxidative damage in neuronal tissue. The present study was undertaken to
      determine the association between functional recovery and vitamin E levels
      following sciatic nerve crush injury in normal and diabetic rats. The sciatic
      nerve of normal and streptozotocin (STZ) induced diabetic rats was crushed using
      a haemostat. The walking track analysis and vitamin E levels were recorded on 10,
      20 and 30th day. Maximum functional deficiency and depletion of vitamin E in
      sciatic nerve was observed on 10th day following crush injury in both normal and
      diabetic animals. A progressive motor recovery and repletion of vitamin E was
      observed on day 20 and 30 following injury in both diabetic and normal rats. The
      functional recovery was slower whereas vitamin E level was higher in diabetic
      animals as compared to normal injured rats during healing phase suggesting that
      vitamin E alone may not be an efficient indicator of oxidative stress during
      regeneration of axons following trauma in diabetic rats.

PMID- 10069625
TI  - The effect of 2-amino-3-arsonopropionate and 2-amino-4-arsonobutyrate on the
      development and maintenance of amygdala kindled seizures.
AB  - The effects of 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate, the arsono
      analogues of aspartate and glutamate respectively, on the development of
      electrically-induced kindling in the amygdala, and on seizures induced in fully
      kindled rats, were compared to the effects of 3-amino-propylarsonate the arsono
      analogue of GABA. Intra-amygdaloid micro-injection of 2-a-3-arsonopropionate and
      2-a-4-arsonobutyrate (10 nmol in 0.5 microl buffer phosphate) reduced the rate of
      epileptogenesis without preventing the development of generalized seizure
      responses, after 14 daily stimulations. In fully electrically kindled animals
      with stage 5 amygdala-kindled seizures, 3-aminopropy-larsonate (10 nmol/0.5
      microl) increased after-discharge threshold (ADT) by 82% (P< or =0.005) without
      having any effect on mean seizure score or after-discharge duration. Chemical
      reduction of 3-aminopropylarsonate with glutathione diminished the anti-seizure
      activity of the drug. 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate the arsono
      analogues of aspartate and glutamate were not effective when they were micro
      injected into the amygdala of fully kindled animals at equivalent doses i.e. (10
      nmol/0.5 microl). Higher doses (100 nmol/0.5 microl) of 2-a-3-arsonopropionate
      the analogue of aspartate increased the generalized seizure threshold by 40% (P <
      or = 0.025), while 2-a-4-arsonobutyrate was not effective even at high doses.

PMID- 10069626
TI  - A preliminary evaluation of emotional experience and expression following
      unilateral brain damage.
AB  - In this preliminary study, hemispheric specialization for the experience and
      expression of emotion was investigated. Subjects were right-brain-damaged (RBD),
      left-brain-damaged (LBD), and normal control (NC) right-handed adults, carefully
      matched on demographic and neurological variables. Facial expressions were
      videotaped while subjects described recollected emotional and nonemotional
      experiences. Expressions were later rated by trained judges for emotional
      intensity and category accuracy. To examine experience, subjects evaluated the
      intensity and accuracy with which they had produced their monologues. RBDs
      produced less intense facial expressions and reported less intense emotional
      experiences than LBDs and NCs. LBDs rated themselves as producing expressions
      with less accuracy than did RBDs and NCs. These findings are consistent with
      research that supports the right-hemisphere hypothesis for emotion. In addition,
      judges' ratings and subjects' self-reports of emotional intensity were positively
      correlated for normal but not for brain-damaged subjects.

PMID- 10069627
TI  - Bias in clinical trials: the importance of suture technique.
AB  - OBJECTIVE: To study the effect on suture technique of introducing a new suture
      material. DESIGN: Prospective clinical study. SETTING: County hospital, Sweden.
      SUBJECTS: 224 patients included during the first 10 months of a clinical study
      that had been designed to compare two suture materials. INTERVENTIONS: Wounds
      were sutured by a continuous technique. The suture length: wound length ratio was
      recorded together with details of patients and operations. MAIN OUTCOME MEASURES:
      The incidence of incisional hernia after 12 months. RESULTS: The mean suture
      length: wound length ratio was 3.6 (95% confidence interval (CI) 3.4 to 3.9) in
      wounds closed with the introduced new material and 3.2 (2.9 to 3.4) with the
      familiar material (p<0.01). With the new material a higher proportion of wounds
      were sutured at a ratio of 4 or more. Incisional hernias developed in 6% (3 of
      50) of wounds sutured with a suture length : wound length ratio of 4 or more and
      in 22% (26 of 119) if it was less (p = 0.01). The rate of incisional hernia was
      lower in wounds sutured with the new suture material. CONCLUSION: During the
      first 10 months of a clinical trial the introduction of a new suture material
      caused a potential systematic error. The suture technique was more meticulous
      with the new material and this may have affected the rate of incisional hernia.
      The suture technique should therefore be monitored in such studies in the future.

PMID- 10069628
TI  - The composition of serous fluid after axillary dissection.
AB  - OBJECTIVE: To analyse the composition of the serous fluid formed after axillary
      dissection. DESIGN: Descriptive study. SETTING: University hospital and teaching
      hospital, The Netherlands. SUBJECTS: 16 patients whose axillas were dissected as
      part of a modified radical mastectomy for stage I or II breast cancer. MAIN
      OUTCOME MEASURES: Chemical and cellular composition of axillary drainage fluid on
      the first, fifth, and tenth postoperative days compared with the same
      constituents in blood and with reported data on the composition of peripheral
      lymph. RESULTS AND CONCLUSION: On the first postoperative day the drainage fluid
      contained blood contents and a high concentration of creatine phosphokinase
      (CPK). After day one it changed to a peripheral lymph-like fluid but containing
      different cells, more protein, and no fibrinogen, making coagulation impossible.
      The reduction in the fluid production must be caused by other wound healing
      processes, such as formation of scars and connective tissue.

PMID- 10069629
TI  - Operations that require supracoeliac aortic cross-clamping: perioperative
      monitoring with gastric tonometry.
AB  - OBJECTIVE: To assess the predictive value of a gastric intramucosal pH of less
      than 7.35 for mortality in surgical patients after supracoeliac aortic cross
      clamping. DESIGN: Open prospective clinical study. SETTING: University hospital,
      The Netherlands. SUBJECTS: Six patients who required temporary supracoeliac, and
      four patients who required temporary infrarenal, cross-clamping of the aorta.
      MAIN OUTCOME MEASURES: Mortality and conventional measures of organ dysfunction
      correlated with gastric tonometry. RESULTS: All 6 patients who required
      supracoeliac cross-clamping underwent a steep, and 5 patients a prolonged,
      decrease in the gastric intramucosal pH. The mean lowest gastric intramucosal pH
      in the supracoeliac group was 7.05 and in the infrarenal group 7.28. All patients
      recovered completely. CONCLUSION: A pHig value below 7.35 does not seem to be a
      marker of mortality in patients who have undergone supracoeliac cross-clamping of
      the aorta.

PMID- 10069630
TI  - Immune response after laparoscopic and conventional Nissen fundoplication.
AB  - OBJECTIVE: To compare the changes in the immune responses of patients undergoing
      laparoscopic or conventional Nissen fundoplication. DESIGN: Prospective
      randomised clinical study. SETTING: University hospital, Finland. SUBJECTS: 20
      patients undergoing Nissen fundoplication for symptomatic erosive oesophagitis.
      INTERVENTION: Laparoscopic Nissen fundoplication (n = 10) or conventional open
      Nissen fundoplication (n = 10). MAIN OUTCOME MEASURES: Leucocyte and differential
      counts; percentages of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD20
      positive lymphocytes); and monocytes (CD 14); phytohemagglutinin, concanavalin A
      and pokeweed mitogen-induced and unstimulated proliferation of separated
      lymphocytes; plasma interleukin-6 (IL-6), serum C-reactive protein (CRP),
      albumin, and cortisol concentrations; and group II phospholipase A2 (PLA2)
      activity. RESULTS: Laparoscopic fundoplication was associated with less tissue
      damage (IL-6, and CRP concentrations) than the conventional open operation.
      However, although there were pronounced changes in immune responses over time,
      there were no differences between the groups. CONCLUSION: Laparoscopic
      fundoplication seemed to cause less tissue damage than the conventional open
      operation, but this difference was not reflected in patients' immune responses.

PMID- 10069631
TI  - Elective transumbilical compared with standard laparoscopic cholecystectomy.
AB  - OBJECTIVE: To compare the transumbilical technique of laparoscopic
      cholecystectomy with standard laparoscopic cholecystectomy. DESIGN: Randomised
      open study. SETTING: Teaching hospital, Italy. SUBJECTS: 90 patients who required
      elective cholecystectomy under general anaesthesia. INTERVENTIONS: Standard
      laparoscopic cholecystectomy through 4 ports or transumbilical cholecystectomy
      through 2 ports. MAIN OUTCOME MEASURES: Amount of pain and analgesia, cost, side
      effects, and cosmesis. RESULTS: 25 patients were excluded from analysis (8 in the
      standard group because relevant data were not recorded; and 17 in the
      transumbilical group in 4 of whom relevant data were not recorded, and 13 for
      technical reasons). 32 patients who had standard, and 25 who had transumbilical
      cholecystectomy had operative cholangiograms. There were no complications, no
      side effects, and no conversions to open cholecystectomy. Those who had
      transumbilical cholecystectomy had significantly lower pain scores (p<0.05) and
      required significantly less analgesia during the first 24 hours (p<0.05) than
      those who had standard laparoscopic cholecystectomy. CONCLUSION: Once the
      learning curve has been completed, transumbilical cholecystectomy is possible
      without some of difficulties associated with standard laparoscopic
      cholecystectomy.

PMID- 10069632
TI  - Phospholipase A2 activity in body fluids and pancreatic tissue in patients with
      acute necrotising pancreatitis.
AB  - OBJECTIVE: To measure pancreatic and non-pancreatic phospholipase A2 activity in
      human acute necrotising pancreatitis. DESIGN: Prospective study. SETTING:
      University hospital, Finland. SUBJECTS: 20 patients with acute necrotising
      pancreatitis. INTERVENTIONS: Serum and urine samples were taken daily for a week
      and fluid from peritoneal lavage for six days after admission. Samples from the
      pleural cavity were taken from patients in whom pleural drainage was considered
      necessary. Pancreatic tissue was recovered from the patients who were operated on
      for acute pancreatitis or for pancreatic tumour. MAIN OUTCOME MEASURES: Serum
      phospholipase A2, amylase, and lipase activities. RESULTS: Serum phospholipase A2
      activity increased up to eightfold, 25.0 (5.4) IU/L (n = 20, range 9.0-77 IU/L)
      (reference value <3 IU/L) and remained high during the first week, whereas serum
      amylase and lipase returned to the reference range during the first four days.
      The maximal phospholipase A2 activity in urine was 4.5 IU/L, in the fluid from
      peritoneal lavage 16.9 IU/L, and in the fluid from the pleural cavity 37.0 IU/L.
      Phospholipase A2 activity in necrotic pancreatic tissue ranged from 0.25 to 5.70
      IU/g and in normal pancreatic tissue from 9.85 to 15.0 IU/g. Preincubation at 60
      degrees C showed non-pancreatic phospholipase A2 activity predominated in serum,
      whereas part of the enzyme activity in the fluids from pleural cavity and
      peritoneal lavage proved to be of pancreatic derivation. CONCLUSIONS: The results
      suggest a role for both pancreatic and non-pancreatic phospholipase A2 in acute
      pancreatitis. Preincubation at 60 degrees C proved useful in the differentiation
      between pancreatic and non-pancreatic phospholipase A2 activity.

PMID- 10069633
TI  - Management of intraductal papillary mucinous tumours of the pancreas.
AB  - OBJECTIVE: To focus attention on the management and outcome of patients with
      intraductal papillary mucinous tumours of the pancreas. DESIGN: Retrospective
      study and analysis of published reports. SETTING: University hospital, France.
      SUBJECTS: 111 patients (101 published cases and our own 10 cases) divided in two
      groups: the first including malignant tumours (n = 46), and the second group
      benign or in situ tumours (n = 61). In 4 patients the type of tumour was not
      known. MAIN OUTCOME MEASURE: Resectability, mortality and recurrence. RESULTS:
      More men had benign or in situ tumours [48/61 (79%) compared with 28/46 (61%), p
      = 0.054]. Pancreatitis was more common among benign than malignant tumours [34/61
      (58%) compared with 21/46 (46%), p = 0.33]. In group I, 39 patients had diabetes.
      A total of 107 patients were operated on: pancreaticoduodenectomy (n = 54, 50%),
      distal pancreatectomy (n = 25, 23%), total pancreatectomy (n = 4,4%), bypass (n =
      2,2%). The type of resection was not mentioned in 22 records (21%). Four patients
      were not operated on because of their poor general condition. The resectability
      rate was 98% (105/107). Eleven patients had died at the time of publication.
      Hospital mortality rate was 3% (n = 3), mainly because 2 of the 4 who had total
      pancreatectomy died. With a median follow-up of 37 months, recurrence was 5% (n =
      5). CONCLUSION: Intraductal papillary mucinous tumours of the pancreas are well
      known distinctive pancreatic tumours that are usually intraductal but may develop
      into invasive carcinoma. They should be resected, and have a good prognosis and
      low recurrence rate.

PMID- 10069634
TI  - Randomised study of Lichtenstein compared with Shouldice inguinal hernia repair
      by surgeons in training.
AB  - OBJECTIVE: To compare the outcome following Lichtenstein open mesh technique or
      Shouldice repair for inguinal hernia operated on by surgeons in training. DESIGN:
      Prospective, randomised, trial. SETTING: District hospital, Sweden. SUBJECTS: 200
      men with primary inguinal hernias. INTERVENTIONS: Lichtenstein mesh repair or
      Shouldice repair. MAIN OUTCOME MEASURES: Duration of operation, postoperative
      pain assessed by visual analogue scale (VAS), complications within 30 days,
      duration of sick leave, and recurrence within one year. RESULTS: 178 patients
      were available for evaluation (n = 89 in each group). There were no significant
      differences in duration of operation, pain score, or incidence of postoperative
      complications. Patients in the mesh group took significantly less sick leave
      (mean 18.2 days) than those in the Shouldice group (23.8 days, p<0.05). The
      number of recurrences differed significantly between the groups with 9 in the
      Shouldice group and none in the mesh group (p<0.01). CONCLUSION: For surgeons in
      training the Lichtenstein open mesh technique is a better method of inguinal
      hernia repair than the Shouldice technique. The outcome is better for the
      patients and it is more cost-effective.

PMID- 10069635
TI  - Influence of age on prognosis and management of patients with colorectal
      carcinoma.
AB  - OBJECTIVE: To see if the prognosis and management differed in patients with
      carcinoma of colon and rectum above and below 65 years of age. DESIGN:
      Retrospective study. SETTING: University hospital, Turkey. SUBJECTS: 822
      consecutive patients with colorectal carcinoma operated on between 1984 and 1994,
      565 of whom were less than 65, and 257 of whom were 65 or more. MAIN OUTCOME
      MEASURES: Factors that affected prognosis and management. RESULTS: There were no
      significant differences between the two groups in mode of presentation, site and
      type of tumour, histological grade, incidence of curative and palliative
      operations, and postoperative morbidity and mortality. Obstruction and
      perforation were more common in the elderly group (p<0.0001). The postoperative
      (30 day) mortality was 3% in the younger group (20/565) and 7% in the older group
      (17/257). It was higher in those who were operated on as emergencies but was not
      significantly related to age. The actuarial five- year survival rates for older
      and younger patients were 33% and 45%, respectively (p<0.05). CONCLUSION: Age
      alone has no characteristic effect on the treatment of colorectal carcinoma.

PMID- 10069636
TI  - Sutureless small bowel anastomoses: experimental study in pigs.
AB  - OBJECTIVE: To evaluate a new technique for experimental anastomosis with fibrin
      glue, and to compare the results with those of stapled and one-layer sutured
      anastomosis. DESIGN: Open laboratory study. SETTING: Teaching hospital, Sweden.
      ANIMALS: Ten Swedish domestic pigs. INTERVENTIONS: Each pig had three anastomoses
      made in the small bowel, one by each technique. The pigs were killed on the 4th
      postoperative day. MAIN OUTCOME MEASURES: Blood flow, collagen concentration,
      anastomotic index, breaking strength, thickness of bowel wall, and histological
      appearance. RESULTS: Two pigs died postoperatively, leaving 8 for analysis. The
      blood flow at each anastomotic site studied by the microsphere technique was
      similar irrespective of the type of anastomosis (p = 0.3), as was anastomotic
      collagen concentration (p = 0.09). The anastomotic index, however, was
      significantly higher in the stapled than in the glued or sutured ones (p = 0.03).
      The glued anastomosis was the weakest, being only one fifth the strength of the
      stapled and one third the strength of the sutured anastomosis. There was no sign
      of rejection of the glue (of human origin) on histological examination. Glued and
      stapled anastomoses showed signs of mild inflammation, which did not reach the
      intensity of that around the sutured anastomoses. CONCLUSION: It is possible to
      make a sutureless anastomosis that does not leak with a modified stapler using
      fibrin glue instead of staples, but the anastomosis has considerably lower
      breaking strength than either stapled or sutured anastomoses.

PMID- 10069637
TI  - Rural surgery, caring for developing communities.

PMID- 10069638
TI  - Total rupture of the gastro-oesophageal junction after blunt trauma.

PMID- 10069639
TI  - Inguinal swelling: a rare presentation of retroperitoneal hydatidosis.

PMID- 10069640
TI  - Relative risk of malignant tumors in analgesic abusers. Effects of long-term
      intake of aspirin.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) e.g. aspirin,
      indomethacin are reported in epidemiological and experimental studies to reduce
      the risk for colo-rectal cancer and potentially other malignant tumors. METHODS:
      We examined the effect of NSAIDs on tumor prevalence in abusers of mixed
      analgesics containing aspirin, phenacetine, caffeine or codein. 618 analgesic
      abusers who were autopsied between 1968-1983 were compared with a control group
      without evidence of analgesic abuse matched for sex, age and year autopsy was
      performed. RESULTS AND CONCLUSIONS: Abusers were found to have an overall risk of
      0.40 fold of having developed a malignancy as compared with the controls.
      Excluding patients with urinary tract tumors which are increased in analgesic
      abusers the risk was further decreased to 0.28. No statistically significant
      effect was found for patients with prostate cancer. The results encourage
      prospective control studies in high risk patients.

PMID- 10069641
TI  - Erythrocyte P1 group antigen expression in VTEC-associated hemolytic uremic
      syndrome.
AB  - BACKGROUND: The P1 blood group antigen has been postulated as a protective host
      factor against the development of the verotoxin-associated with hemolytic uremic
      syndrome (HUS). PATIENTS AND METHODS: In this study the P1 blood group antigen in
      59 Japanese children with a past history of hemorrhagic colitis (HC) was scored
      with a direct agglutination method using a commercial anti P1 antibody. RESULTS:
      The P1 antigen was positive in 4 (21.1%) of 19 patients with a history of
      postdiarrheal HUS and in 11 (28.0%) of 40 patients with no history. There were no
      significant differences in the frequency of the P1 phenotype between the 2 groups
      (p = 0.629). CONCLUSION: We concluded that the P1 blood group antigen is not a
      protective factor against the development of HUS from verotoxin-producing
      Escherichia coli(VTEC)-infected hemorrhagic colitis in Japanese individuals.

PMID- 10069642
TI  - Prevalence of hypertension in a hemodialysis population.
AB  - BACKGROUND: Accurate information on prevalence and status of blood pressure (BP)
      control in hemodialysis patients is lacking. Our Hemodialysis Quality Improvement
      Program, sought to determine: 1) The extent and control of hypertension (HTN), 2)
      whether Erythropoietin (EPO) dose or intradialytic fluid loss had any effect on
      BP and 3) a means to follow the severity of HTN. PATIENTS AND METHODS: The
      pre/post mid-week dialysis BP readings of 190 patients (64+/-14.1 years, 53%
      males, 77% whites) were evaluated over a 3 month period. HTN was defined as BP
      >150/90. Hypertension was further characterized according to whether the patients
      had normal or elevated pre-dialysis systolic, pre-dialysis diastolic, post
      dialysis systolic or post-diastolic BP readings on more than 6 of the possible 13
      recordings. The average EPO dose and weight loss during dialysis was correlated
      with BP. To better understand the extent of HTN, systolic and diastolic pressures
      were separately graded from 0 to 3 and a number designated as hypertension
      sensitivity index (HSI) was assigned to each patient. RESULTS: Of the 190
      patients, 146 (76.8%) were hypertensive. 117 out of 146 hypertensive patients
      (80.1%) had persistent elevation of BP despite being on one or more
      antihypertensive medications. Most patients were on calcium channel blockers
      (39%) with 27% being on beta-blockers and 14% on Angiotensin converting enzyme
      inhibitors. There was no correlation between the number of medications used and
      the control of HTN. The dose of EPO also had no effect on the degree of HTN.
      69.8% of all HTN was systolic. Of this, 64.7% was pre-dialysis and 35.3% post
      dialysis. Multiple regression analysis demonstrated a significant correlation
      with loss of weight during dialysis and lowering of systolic BP (r = 0.33, p =
      0.0001). The mean HSI for this population was 2.3+/-1.8. CONCLUSION: HTN was a
      frequent finding in our hemodialysis population and it was controlled in only
      19.9% of hypertensive patients. Most of this HTN was pre-dialysis systolic. There
      was a significant correlation between fluid loss during dialysis and lowering of
      blood pressure. The use of the HSI has proven to be helpful in differentiating
      type and severity of HTN.

PMID- 10069643
TI  - Differential kinetics of circulating angiotensin IV and II after treatment with
      angiotensin II type 1 receptor antagonist and their plasma levels in patients
      with chronic renal failure.
AB  - BACKGROUND: Angiotensin II (Ang II) C-terminal hexapeptide (referred to as Ang
      IV) possesses the characteristics of a real hormone with specific receptors and
      biological effects. Clinical application of Ang II type 1 receptor (AT1-R)
      antagonists cause an increase in plasma Ang II level, which may result in
      enhanced production of Ang IV. PATIENTS AND METHODS: In this study, we measured
      plasma Ang IV and Ang II levels in patients with chronic renal failure (CRF), and
      also examined the changes in Ang IV and Ang II levels after administration of an
      ATI-R antagonist. RESULTS: Ang II and Ang IV levels in CRF patients untreated
      with hemodialysis (n = 16) were 15.8+/-3.6 and 6.0+/-1.1 pg/ml, respectively,
      which did not differ significantly from Ang II (20.6+/-2.4) and Ang IV levels
      (8.6+/-1.1) in normal controls (n = 23). The ratio of Ang IV to Ang II was 38%,
      similar to that in the controls (41%). Ang II or Ang IV levels in CRF patients
      treated with hemodialysis (n = 12) were also similar to the control values. Ang
      IV levels had a significant correlation with Ang II levels (r = 0.59). When
      hypertensive patients were treated with an AT1-R antagonist candesartan for 7
      days, Ang II and Ang IV levels were increased 5.5- and 4.1-fold relative to the
      control levels, respectively. Ang II levels 28 and 56 days after treatment were
      significantly lower than those 7 days after treatment, whereas Ang IV levels did
      not differ significantly from those 7 days after treatment. Similar differential
      kinetics in Ang II and Ang IV levels after long-term (90 days) treatment with an
      AT1-R antagonist was also confirmed in experiments using rats. Significant
      decrease in blood pressure continued during long-term treatment with an AT1-R
      antagonist. CONCLUSION: These findings demonstrated that plasma Ang IV levels in
      patients with CRF did not differ significantly from those in normal subjects, and
      that treatment with an AT1-R antagonist caused marked increases in both Ang II
      and Ang IV levels. In contrast, during long-term treatment plasma Ang II levels
      were more rapidly decreased than Ang IV levels, suggesting longer-lasting
      enhancement of the action of Ang IV rather than that of Ang II after treatment
      with an AT1-R antagonist.

PMID- 10069644
TI  - Hypoalbuminemia accelerates erythrocyte membrane lipid peroxidation in chronic
      hemodialysis patients.
AB  - BACKGROUND: Persistent hypoalbuminemia is a long-term poor prognostic factor in
      chronic hemodialysis patients. PATIENTS AND METHODS: We investigated the
      correlation between the degree of peroxidation of erythrocyte membrane lipids,
      erythrocyte alpha tocopherol content, erythrocyte glutathione peroxidase activity
      and serum albumin concentration in twelve patients with uremia not undergoing
      hemodialysis and fifteen patients on maintenance hemodialysis. RESULTS: The
      glutathione peroxidase activity in erythrocytes was higher in patients of uremia
      not undergoing hemodialysis than in chronic hemodialysis patients. A significant
      negative correlation was observed between the erythrocyte alpha tocopherol
      content and the degree of erythrocyte membrane lipid peroxidation in chronic
      hemodialysis patients. There was a statistically significant difference in the
      degree of erythrocyte membrane lipid peroxidation between patients with chronic
      hemodialysis-associated hypoalbuminemia and chronic hemodialysis patients having
      normal serum albumin levels. CONCLUSION: This study suggested that serum albumin
      inhibits peroxidation of erythrocyte membrane lipids and that hemodialysis
      induces recovery of serum reductivity. We conclude that persistent
      hypoalbuminemia worsens the serum antioxidant activity in chronic hemodialysis
      patients and may contribute to increased oxidative cell damage.

PMID- 10069645
TI  - Renal vasoconstriction induced by oxidized LDL is inhibited by scavengers of
      reactive oxygen species and L-arginine.
AB  - BACKGROUND: Low density lipoprotein (LDL) may be involved in the pathogenesis of
      glomerulosclerosis and progressive renal dysfunction associated with
      atherosclerotic renal artery stenosis (RAS). This study was undertaken to
      investigate the effects of native (n-LDL) and oxidized LDL (ox-LDL) on renal
      vascular response and function in an isolated perfused rat kidney (IPRK) model.
      MATERIAL AND METHOD: IPRK model was used for the study at a constant pressure of
      100 mm of Hg in the renal artery with continuous monitoring of pressure and renal
      perfusate flow. Urine and perfusate samples were collected to determine [14C]
      Inulin clearance and fractional reabsorption of sodium. To elucidate the role of
      nitric oxide (NO) urinary c-GMP, nitrate and nitrite excretion were measured and
      the responses to the NO synthase inhibitor N-monomethyl-L-arginine (LNMMA) and
      the NO donor Nitroso-glutathione (GSNO) were assessed. The effect of L-arginine
      supplementation and the role of reactive oxygen species were also studied by
      adding superoxide dismutase (SOD) and catalase. RESULTS: Ox-LDL but not n-LDL
      caused vasoconstriction in IPRK, as evidenced by a significant dose dependent
      reduction in renal perfusate flow. [14C] Inulin clearance and fractional
      reabsorption of sodium were reduced during ox-LDL infusion whereas no significant
      change occured with n-LDL. There was a significant decrease in urinary excretion
      of c-GMP during ox-LDL infusion. 10 microM LNMMA significantly increased and GSNO
      (10 microM) significantly diminished the vasoconstrictory effect of ox-LDL. The
      presence of L-arginine (100 & 500 microM) significantly decreased ox-LDL induced
      vasoconstriction. SOD (150 U/ml) and catalase (1200 U/ml) both had a significant
      inhibitory effect and the combination of SOD and catalase almost completely
      abolished the vasoconstriction due to ox-LDL. CONCLUSION: These results suggest
      that ox-LDL induced vasoconstriction in IPRK is mediated by decreased activity of
      NO probably due to inactivation of NO by reactive oxygen species. The free
      radical scavengers SOD, catalase and L-arginine provided protection against ox
      LDL induced vasoconstriction in this model.

PMID- 10069646
TI  - Response of hyperhomocysteinemia to folic acid supplementation in patients with
      end-stage renal disease.
AB  - BACKGROUND: Elevated concentrations of homocysteine are associated with an
      increased risk for cardiovascular disease. Reasons for elevated homocysteine
      concentrations are folate or vitamin B12 deficiency, renal disease or genetic
      abnormalities. A high prevalence of hyperhomocysteinemia is found in patients
      with end-stage renal disease (ESRD). Since these patients are also at increased
      risk for vitamin deficiency, a supplementation study comparing two doses of folic
      acid was performed in patients with ESRD treated with maintenance hemodialysis or
      with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis
      (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg
      folic acid (three times per week after each dialysis treatment) for four weeks in
      a parallel study design. In 20 hemodialysis patients, the effect of folic acid
      withdrawal was observed after four weeks. RESULTS: Both supplementation schemes
      reduced homocysteine to a similar extent (35%) but did not normalize homocysteine
      concentrations in the majority of patients. Dialysis also had a strong
      homocysteine lowering effect. After supplementation, 74% of the hemodialysis
      patients had post-dialysis homocysteine concentrations within the reference range
      (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients
      four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is
      concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect
      on homocysteine concentrations to supplementation regimens using 15 mg folic acid
      supplements. In contrast to the effect of folic acid supplementation in subjects
      with normal renal function, folic acid supplementation does not normalize
      homocysteine concentrations in ESRD patients.

PMID- 10069647
TI  - A large prospective survey of anti-cardiolipin antibodies in chronic hemodialysis
      patients.
AB  - We prospectively measured anti-cardiolipin antibody (ACLA) levels in 230 chronic
      hemodialysis (HD) patients over a 2-year period. Twenty-nine percent of HD
      patients were found to have elevated IgG-ACLA titers. Males were more likely to
      have elevated IgG-ACLA titers. Elevated IgG-ACLA titers correlated with shortened
      AVG survival in HD-patients (mean of 156 vs. 238 days, p<0.05). There was no
      statistically significant correlation with access survival in AVF-patients. There
      seemed to be a higher mean IgG-ACLA titer in diabetics but they did not have
      statistically significant shorter angioaccess survival times. By logistic
      regression analysis, only IgG-ACLA positivity was predictive of premature
      angioaccess failure (p<0.05). In a selected subset of 16 patients with frequent
      angioaccess (AVG) failure and elevated IgG-ACLA levels, coumadin, titrated to an
      INR of 2 - 3, was found to produce a small (though statistically significant)
      prolongation of AVG survival.

PMID- 10069648
TI  - Intravesicular formaldehyde instillation and renal complications.
AB  - Intravesicular formaldehyde has been used for intractable hemorrhagic cystitis
      since the late 1960's. Initial reports described few complications, but in the
      1970's both ureteral as well renal parenchymal damage were reported in the
      urology literature. This has been less appreciated by nephrologists perhaps
      related to the paucity of reports in the nephrology literature. Although the
      pathogenesis has not been rigorously studied ureteral toxicity may be secondary
      to intense edema, inflammation and subsequent fibrosis induced by the
      formaldehyde; while renal tubular injury may be secondary to systemic absorption
      of formaldehyde. Ureteral reflux as well as dosage of intravesicular formaldehyde
      seem to be risk factors for acute renal failure. We describe a case of acute
      renal failure secondary to intravesicular formaldehyde and review pathogenesis as
      well as potential prophylactic measures to prevent this complication.

PMID- 10069649
TI  - Peritoneal calcification in continuous ambulatory peritoneal dialysis.

PMID- 10069650
TI  - Successful combined therapy of nifedipine and diltiazem for severe hypertension
      in a maintenance hemodialysis patient.

PMID- 10069651
TI  - Long-term persistence of hepatitis C viremia in hemodialysis patients.

PMID- 10069652
TI  - Computer-assisted light microscopy in evaluating urinary red blood cell
      morphology.

PMID- 10069653
TI  - Significance of medial hypertrophy of blood vessels in IgA nephritis.

PMID- 10069654
TI  - Oestrogen deficiency in men: where are we today?

PMID- 10069655
TI  - Interactions between the neuropeptide Y system and the hypothalamic-pituitary
      adrenal axis.
AB  - The aim of this paper is to review the present knowledge of interactions between
      the neuropeptide Y (NPY) system and the hypothalamic-pituitary-adrenal (HPA)
      axis. On the basis of in vitro and in vivo studies of various animal species, we
      review the effects of NPY on all levels of HPA axis activity. We also describe
      the effects of glucocorticosteroids on the NPY system in the hypothalamus,
      including interactions between glucocorticosteroids and insulin. On the basis of
      available literature, we discuss the role of these interactions in the control of
      food intake and in the pathogenesis of obesity.

PMID- 10069656
TI  - Aquaporin-2 water channel mutations and nephrogenic diabetes insipidus: new
      variations on a theme.

PMID- 10069657
TI  - Kleine-Levin and Munchausen syndromes in a patient with recurrent acromegaly.
AB  - Hypothalamic disease often affects the patients' personality and this also
      applies to pituitary tumors with suprasellar extension. We report on a patient
      with a 12-year history of recurrent acromegaly, treated with three transphenoidal
      operations, single field radiation therapy and bromocriptine/octreotide
      administration. During the course of follow-up she presented with self-inflicted
      anemia and Kleine-Levin syndrome (hypersomnia, hyperphagia and hypersexuality).
      Furthermore, she developed post-radiation necrosis within the right temporal
      lobe. Whether her neurological and personality disorders result - at least
      partially - from the acromegaly or the temporal lobe necrosis remains unclear.

PMID- 10069658
TI  - The elevated serum alkaline phosphatase--the chase that led to two
      endocrinopathies and one possible unifying diagnosis.
AB  - A 39-year-old Chinese man with hypertension being evaluated for elevated serum
      alkaline phosphatase (SAP) levels was found to have an incidental right adrenal
      mass. The radiological features were characteristic of a large adrenal
      myelolipoma. This mass was resected and the diagnosis confirmed pathologically.
      His blood pressure normalised after removal of the myelolipoma, suggesting that
      the frequently observed association between myelolipomas and hypertension may not
      be entirely coincidental. Persistent elevation of the SAP levels and the
      discovery of hypercalcaemia after surgery led to further investigations which
      confirmed primary hyperparathyroidism due to a parathyroid adenoma. The patient's
      serum biochemistry normalised after removal of the adenoma. The association of
      adrenal myelolipoma with primary hyperparathyroidism has been reported in the
      literature only once previously. Although unconfirmed by genetic studies this
      association may possibly represent an unusual variation of the multiple endocrine
      neoplasia type 1 syndrome.

PMID- 10069659
TI  - Undetectable urinary free cortisol concentrations in a case of Cushing's disease.
AB  - Measurement of the 24-h urinary free cortisol is a valuable screening test of
      endogenous hypercortisolism and, although false positive results may occur in a
      few situations, for example endogenous depression, false negative results are
      unusual. We report a case of a 48-year-old lady with pituitary-dependent
      Cushing's disease, whose 24-h urinary free cortisol excretion was consistently
      undetectable in association with increased plasma and salivary cortisol
      concentrations and reduced dexamethasone suppressibility. The patient had chronic
      renal impairment (creatinine clearance 21 ml/min) as a consequence of
      hypertension, despite only modestly increased urea and creatinine concentrations.
      Urinary free cortisol measurements must be interpreted with caution in patients
      with renal impairment.

PMID- 10069660
TI  - IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas.
AB  - Several cytokines have been shown to be expressed in normal and adenomatous
      pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse
      transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We
      have investigated further the presence of IL-8 mRNA, using in situ hybridisation
      in two normal human anterior pituitary specimens and 25 human pituitary adenomas.
      IL-8 mRNA was not identified in either of the two normal pituitary specimens.
      Only three of the 25 adenomas were positive for IL-8 mRNA. In these three
      tumours, which included two null cell adenomas and one gonadotrophinoma, the
      majority of tumour cells (>90%) were positive for IL-8 mRNA. The remaining 22
      adenomas were completely negative. There was no difference in tumour size or type
      between the IL-8 positive and the IL-8 negative tumours, and immunocytochemistry
      for von Willebrandt factor showed that the two groups were also similar in their
      degree of vascularisation. In conclusion, IL-8 mRNA was found in 12% of pituitary
      adenomas studied and was histologically identified within the tumour cells. In
      situ hybridisation is a more appropriate technique for assessing cytokine mRNA
      production by human pituitary tumours because RT-PCR may be too sensitive,
      identifying very small, possibly pathologically insignificant, quantities of mRNA
      that could be produced by supporting cells such as fibroblasts, endothelial cells
      or macrophages.

PMID- 10069661
TI  - GH-binding protein in obese men with varying glucose tolerance: relationship to
      body fat distribution, insulin secretion and the GH-IGF-I axis.
AB  - Bioelectrical impedance for measurement of total body fat and computed tomography
      for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese
      and 10 lean men. Insulin secretion in response to an oral glucose tolerance test
      (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP)
      and IGF-I were measured. Obese subjects were divided into three groups according
      to the OGTT. The obese type II diabetes mellitus group had the highest GHBP
      levels and the most visceral fat. GHBP levels were most strongly correlated with
      the ratio of visceral fat area to body weight (VWR) above any other parameters (r
      = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC)
      during the OGTT, and the IGF-I level, were also positively correlated with GHBP
      levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to
      the L-dopa stimulation test was negatively correlated with GHBP levels (r = 
      0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR,
      FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2
      = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly
      determined GHBP levels in obese men with varying glucose tolerance: (ii)
      hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA
      could play a role in regulation of GHBP: and (iii) although GH was not the main
      regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests
      that increased GHBP levels reflect GH hypersensitivity in order to compensate for
      decreased GH secretion in obesity.

PMID- 10069662
TI  - Serum IGF-binding protein-6 and prostate specific antigen in breast cancer.
AB  - OBJECTIVE: Recent studies have demonstrated the presence of the IGF-binding
      proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in
      human breast tissue. We sought to investigate the differences in serum IGFs,
      IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer
      and patients with benign breast disease. DESIGN AND METHODS: Concentrations of
      IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients
      with breast cancer (CA), and 46 women with benign breast disease (BBD) using
      immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. RESULTS:
      The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was
      statistically significantly lower than in the BBD group, 157 (10) ng/ml (P =
      0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018
      (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in
      women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly
      lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P =
      0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus
      the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002)
      respectively. In the CA group, statistically significant correlations between PSA
      and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P =
      0.021) were seen. Differences in IGF-I and -II between the two groups were not
      statistically significant. CONCLUSION: Lower serum concentrations of IGFBP-6, -3
      and -1, but higher PSA concentrations were seen in the breast cancer group, and
      collectively these would suggest that there is an increase in bioavailable IGF-I
      in breast cancer.

PMID- 10069663
TI  - Overexpression of fibroblast growth factor receptor 3 in a human thyroid
      carcinoma cell line results in overgrowth of the confluent cultures.
AB  - Recent reports indicate that a gain-of-function mutation in fibroblast growth
      factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth
      plates. These results suggest that FGFR-3 may be the receptor transducing growth
      inhibitory signals. Using reverse transcription-PCR we examined seven papillary
      thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary
      carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma,
      FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell
      line. High levels of FGFR-3 protein were identified in cells stably transfected
      with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of
      these cells was threefold higher than that of control cells. Growth rates of
      cells overexpressing FGFR-3 were similar to those of control cells. However,
      cells overexpressing FGFR-3 continued to grow beyond the density at which control
      cells stopped proliferating. These results suggest that FGFR-3 in thyroid
      carcinoma is not involved strongly in the cell proliferation mechanism but may
      contribute to the malignant extension of some of the carcinomas by modifying cell
      contact signaling.

PMID- 10069664
TI  - Apo E phenotype and changes in serum lipids in adult patients during growth
      hormone replacement.
AB  - OBJECTIVE: To determine whether apo E phenotype influences changes in lipid
      profiles induced by growth hormone replacement in growth hormone (GH)-deficient
      adults. DESIGNS: Patients were treated for 6 months with recombinant human GH
      (hGH), given in a dose of 0.125 U/kg per week for 4 weeks followed by 0.25 U/kg
      per week thereafter. The effects on serum lipids and the influence of apo E
      phenotype were examined. METHODS: Thirty patients (aged 35.1+/-11.8 years: mean
      +/- S.D.) with adult growth hormone deficiency with included in the study.
      Fasting serum samples were analysed for apo E phenotype total cholesterol, high
      density lipoprotein (HDL)-cholesterol, triglycerides, lipoprotein (a) (Lp(a)) and
      IGF-I. Low-density lipoprotein (LDL)-cholesterol was calculated using the
      Friedwald formula. RESULTS: Six months of replacement treatment with hGH resulted
      in a reduction in HDL-cholesterol from 0.90+/-0.10 to 0.68+/-0.08 mmol/l
      (P<0.01), and a small, non-significant reduction in total cholesterol from 6.14+/
      0.40 to 5.99+/-0.35 mmol/l (P = 0.06). There was no significant change in the
      other lipid parameters. The decrease in HDL-cholesterol concentration was greater
      in patients carrying the apo E2 allele (0.40+/-0.07 mmol/l, P<0.05) than in
      patients homozygous for the apo E3 allele (0.23+/-0.04 mmol/l) and patients
      carrying the apo E4 allele (0.15+/-0.36 mmol/l). Patients with the apo E4 allele
      had lower baseline cholesterol concentrations than patients lacking the apo E4
      allele, and this persisted after treatment with hGH (P<0.05). CONCLUSIONS: Apo E
      phenotype may be a determining factor in the response of HDL-cholesterol to hGH
      in GH-deficient adults.

PMID- 10069665
TI  - Analysis of the relationship between fasting serum leptin levels and estimates of
      beta-cell function and insulin sensitivity in a population sample of 380 healthy
      young Caucasians.
AB  - OBJECTIVE: Circulating leptin levels correlate positively with the degree of
      obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover,
      insulin secreting beta-cells express functional leptin receptors indicating a
      functional relationship between leptin and insulin. The aim of this study was to
      examine the relationship between fasting serum leptin levels and measures of
      insulin sensitivity and beta-cell function in a population-based sample of 380
      young healthy Caucasians. DESIGN AND METHODS: Multiple regression analysis was
      employed to analyse the relationship between fasting serum leptin levels and
      levels of fasting serum insulin, insulin sensitivity index and acute insulin
      response (AIR) in a population-based study of 380 young healthy Caucasians who
      underwent a combined intravenous glucose and tolbutamide tolerance test. RESULTS
      AND CONCLUSION: Serum leptin levels were positively correlated to measures of
      adiposity and were 3.2 times higher in women than in men (P<0.00001). In multiple
      regression analyses adjusting for age, percentage body fat, waist circumference
      and maximal aerobic capacity, a significant positive correlation was observed
      between the fasting serum leptin concentrations and both fasting serum insulin
      levels (P<0.0001) and AIR (P = 0.014) for women. No significant interrelation of
      these variables was found in men. However, for both genders a significant
      negative correlation was observed between fasting serum leptin levels and
      measures of insulin sensitivity index (P = 0.007).

PMID- 10069666
TI  - Inactivating mutations of the LH receptor gene: more than two different
      phenotypes.

PMID- 10069667
TI  - Angiotensin II AT1-receptor blockade inhibits monocyte activation and adherence
      in transgenic (mRen2)27 rats.
AB  - This study investigated whether angiotensin II AT1-receptor blockade with
      losartan inhibits endothelium-monocyte interactions originating from long-term
      activation of the renin-angiotensin system in hypertensive transgenic rats
      [TGR(mRen2)27]. The number of circulating activated monocytes, monocytes adhered
      to thoracic aorta endothelium, and the extent of endothelial cell injury were
      compared in adult male transgenic (mRen2)27 and age-matched Hannover Sprague
      Dawley (SD) rats after 12 days of continuous subcutaneous administration of
      saline (120 microl/24 h), losartan (10 mg/kg/24 h), or the vasodilator
      hydralazine (3 mg/kg/24 h). At the doses administered in this experiment, both
      losartan and hydralazine normalized mRen2 rat blood pressures equal to values in
      similarly treated SD rats. Compared with saline infusion, administration of
      either antihypertensive in mRen2 rats reduced (p<0.05) endothelial cell injury,
      but only losartan significantly (p<0.05) decreased the number of activated
      circulating and endothelium-adherent monocytes. Infusion of antihypertensives in
      SD rats had no effect on blood pressures, monocyte activity, or endothelial
      injury compared with saline administration. These findings suggest that the
      recruitment and infiltration of leukocytes into the subendothelium associated
      with renin-angiotensin system-induced hypertension is partly mediated by pressure
      independent AT1-receptor pathways.

PMID- 10069668
TI  - Frequency-dependent effects of 4-aminopyridine and almokalant on action-potential
      duration of adult and neonatal rabbit ventricular muscle.
AB  - The effects of 4-aminopyridine (1 mM) and almokalant (1 microM) on action
      potential duration of neonatal and adult rabbit ventricular multicellular
      preparations and plateau membrane currents of single ventricular myocytes were
      studied. In adult ventricular preparations, 4-aminopyridine increased action
      potential duration in a frequency-dependent manner, with a greater effect at low
      stimulation frequencies ("reverse" use dependence). In neonatal preparations, the
      increase in action-potential duration by 4-aminopyridine was significantly
      smaller than in adults, and the effect was frequency independent. Almokalant
      increased the action-potential duration more in neonatal than in adult myocytes.
      The effect of almokalant was frequency independent between 0.5 and 2 Hz. The
      block of transient outward current and delayed rectifier current in single
      myocytes was quantitatively similar. We propose that differences in the kinetic
      behavior of the transient outward current between adult and neonatal ventricular
      preparations, slower inactivation, and recovery from inactivation in adults
      determine differences in the frequency-dependent changes induced by 4
      aminopyridine and almokalant on action-potential duration.

PMID- 10069669
TI  - Effects of long-term caffeine consumption on renal function in spontaneously
      hypertensive heart failure prone rats.
AB  - Our previous studies supported the hypothesis that prolonged administration of
      caffeine to animals with high-renin hypertension causes progressive deterioration
      of renal function. However, thus far this hypothesis has been tested with only a
      few animal models of hypertension. The aim of this study was to test this
      hypothesis further by investigating the effects of long-term caffeine consumption
      on renal function in adult spontaneously hypertensive heart failure (SHHF/Mcc
      fa(cp)) rats, another model of high-renin hypertension. Lean, male, 9-month-old
      SHHF/Mcc-fa(cp) rats were randomized to receive either normal drinking water
      (control group) or drinking water containing 0.1% caffeine (caffeine group) for
      20 weeks. No changes in body weight, food and fluid intake, urine volume, and
      sodium and potassium excretion were found in conscious SHHF/Mcc-fa(cp) rats after
      10 or 20 weeks of caffeine treatment. However, caffeine treatment accelerated the
      time-related decline in renal function and augmented urinary protein excretion.
      Ten weeks into the protocol, creatinine clearance was 3.6+/-0.4 and 5.7+/-0.9
      L/kg/day in the caffeine group and control group, respectively (p<0.02), whereas
      20 weeks into the study, creatinine clearance was similarly diminished in both
      groups. Proteinuria was greater in the caffeine group compared with the control
      group at both 10 (928+/-131 vs. 439+/-21 mg/kg/day, respectively; p<0.02) and 20
      weeks (1,202+/-196 vs. 603+/-30 mg/kg/day, respectively; p<0.01) into the
      protocol. After 20 weeks, all animals were anesthetized and instrumented.
      Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or
      vascular resistance in four examined vascular beds (abdominal aorta and renal,
      carotid, and mesenteric arteries). No changes in renal hemodynamics and
      electrolyte excretion were found, whereas significantly lower glomerular
      filtration rate (GFR; inulin clearance) and creatinine clearance (p<0.05) were
      observed in caffeine-treated animals. These data support our hypothesis that
      prolonged consumption of caffeine has adverse effects on renal function, in high
      renin hypertension.

PMID- 10069670
TI  - Characterization of angiotensin II antagonism displayed by SK-1080, a novel
      nonpeptide AT1-receptor antagonist.
AB  - The pharmacologic profile of SK-1080, a nonpeptide AT1-selective angiotensin
      receptor antagonist, was investigated by receptor-binding studies, functional in
      vitro assays with rabbit and rat aorta, and in vivo experiments in pithed rats.
      SK-1080 inhibited the specific binding of [125I]-[Sar1, Ile8]-angiotensin II to
      human recombinant AT1 receptor with a 12-fold greater potency than losartan
      [median inhibitory concentration (IC50): 1.01 and 12.3 nM, respectively], but it
      did not inhibit the binding of [125I]-CGP 42112A to human recombinant AT2
      receptor (IC50: >10 microM for both). The Hill coefficient for the competition
      curve of SK-1080 against AT1 receptor was not significantly different from unity
      (0.96). Scatchard analysis showed that SK-1080 interacted with human recombinant
      AT1 receptor in a competitive manner, as with losartan. In functional studies
      with rat and rabbit aorta, SK-1080 competitively inhibited the contractile
      response to angiotensin II (pKB values: 9.97 and 9.51, respectively) with 15-25%
      decrease in the maximal contractile responses, unlike losartan, which showed
      competitive antagonism without any change in the maximal contractile responses to
      angiotensin II (pA2 values, 8.02 and 7.59, respectively). In pithed rats, SK-1080
      (i.v.) induced a nonparallel right shift in the dose-pressor response curve to
      angiotensin II (ID50, 0.07 mg/kg) with a dose-dependent reduction in the maximal
      responses; this antagonistic effect was approximately 25 times more potent than
      losartan (ID50, 1.74 mg/kg), which showed competitive antagonism. SK-1080 did not
      alter the responses induced by other agonists such as norepinephrine, KCI, and
      vasopressin in isolated rabbit aorta and pithed rats. These results suggest that
      SK-1080 is a highly potent AT1-selective angiotensin II-receptor antagonist with
      a mode of insurmountable antagonism.

PMID- 10069671
TI  - In vivo pharmacologic profile of SK-1080, an orally active nonpeptide AT1
      receptor antagonist.
AB  - The pharmacologic profile of SK-1080, a newly synthesized AT1-receptor
      antagonist, was evaluated in conscious normotensive rats, conscious renally
      (RHRs) and spontaneously (SHRs) hypertensive rats, and conscious furosemide
      treated beagle dogs. In angiotensin II-challenged normotensive rats, orally
      administered SK-1080 had no agonistic effect and dose-dependently inhibited the
      pressor response to angiotensin II with a slightly weaker potency (ID50: 1.12 and
      0.47 mg/kg, respectively), but with a more rapid onset of action than losartan
      (time to Emax, 30 min and 6 h, respectively). In RHRs, orally given SK-1080
      produced a dose-dependent and long-lasting (>24 h) antihypertensive effect with a
      potency similar to that of losartan (ED20, 5.06 and 3.36 mg/kg, respectively).
      Intravenously administered SK-1080 exerted a very highly potent antihypertensive
      effect (ED20, 0.06 mg/kg), thus indicating a poor oral bioavailability in rats.
      On repeated dosing for 21 days in SHRs, SK-1080 significantly reduced blood
      pressure without inducing tachycardia and tolerance throughout the dosing period.
      On repeated dosing, the antihypertensive effect gradually increased from days 1
      to 7 (Emax on day 7, 15.0 and 19.7% at 10 and 30 mg/kg, respectively) and
      remained at a significant level on days 14 and 21. In furosemide-treated dogs,
      orally given SK-1080 produced a dose-dependent and long-lasting (>8 h)
      antihypertensive effect with a rapid onset of action (time to Emax, 1-1.5 h) and
      10-fold greater potency than losartan (ED20, 0.72 and 8.13 mg/kg, respectively).
      In furosemide-treated dogs, SK-1080 showed a good oral bioavailability, unlike
      that in RHRs. These results suggest that SK-1080 is a potent, orally active AT1
      receptor antagonist useful for the treatment of hypertension.

PMID- 10069672
TI  - Verapamil reduces dipyridamole-induced myocardial ischemia in patients with
      coronary artery disease.
AB  - The aim of this study was to evaluate the effects of verapamil administration on
      dipyridamole-induced transient wall-motion abnormalities as detected by two
      dimensional echocardiographic monitoring in patients with coronary artery
      disease. Twenty-eight patients (16 men and 12 women; mean age, 60+/-7 years) with
      angiographic evidence of significant coronary artery disease, positive
      dipyridamole echocardiography test results at basal condition on two consecutive
      days, were prospectively studied. Patients were randomized to verapamil (360
      mg/day) or placebo treatments, given in three divided doses daily for 7 days; at
      the end of this time, each patient crossed over to the alternate regimen.
      Dipyridamole echocardiographic testing was repeated at the end of each treatment
      period. Our data demonstrate that verapamil significantly reduces the
      dipyridamole-induced wall-motion score index, a quantitative marker of acute
      myocardial ischemia (1.7+/-0.4 vs. 1.3+/-0.2; p<0.001). Hemodynamic data show
      that the drug reduces heart rate and rate-pressure product at basal condition
      (heart rate from 75+/-8 to 67+/-9 beats/min; p<0.001; rate-pressure product from
      99+/-13 to 86+/-13 U x 10(-2); p<0.001) and at peak dipyridamole infusion (heart
      rate from 96+/-8 to 89+/-6 beats/min; p<0.001; rate pressure product from 127+/
      21 to 118+/-13 U x 10(-2); p<0.05) with respect to placebo treatment. We conclude
      that verapamil is able to reduce dipyridamole-induced ischemia, as detected by
      two-dimensional echocardiographic monitoring, in patients with coronary artery
      disease by reducing, at least partially, myocardial oxygen consumption. Moreover,
      its beneficial action could be related to the effects of the drug on coronary
      collateral circulation and on sympathetic modulation.

PMID- 10069673
TI  - Pharmacologic study of muscarinic receptor subtypes and arteriolar dilations: a
      comparison of conducted and local responses.
AB  - Arteriolar relaxation caused by the application of muscarinic agonists is
      mediated by multiple factors. One factor causes dilation only at the point of
      drug microapplication (local response), and a second factor causes responses
      remote (500 microm away) from the site of application (conducted response). This
      study was performed to determine if different muscarinic subtypes mediate the two
      responses. Arterioles of anesthetized hamster cheek pouch were studied with
      videomicroscopy. Muscarinic antagonists methscopolamine, scopolamine,
      pirenzepine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide), and AFDX
      116 [(11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H
      pyrido [2,3-b][1,4]benzodiazepin-6-one)] were cumulatively applied, and the K(B)
      for each antagonist was determined for the local and conducted responses caused
      by methacholine microapplication (10(-4) M, 5 s). The pK(B) (local, conducted)
      were not significantly different for the two responses when using scopolamine
      (10.5, 10.4). When the antagonist AFDX-116 (5.6, 6.3), selective for muscarinic
      receptor (m2) subtype was applied, the K(B) was greater for the conducted
      response. The pK(B) was greater, however, for the local response when the m1
      subtype-selective pirenzepine (7.7, 6.9) or m3 subtype-selective 4-DAMP (10.1,
      9.8) was applied. Thus the antagonist pK(B) ratio for on the local and conducted
      responses depends on the subtype selectivity of the antagonist. These data
      strongly suggest that different receptors are involved in the two responses.

PMID- 10069674
TI  - Cytosolic myocardial calcium modulation by ATP-dependent potassium channel
      openers and NO donors.
AB  - The goal of this study was to evaluate, in rat cardiomyocytes, the effects on
      cytosolic calcium of a pure K-adenosine triphosphate (ATP) channel opener,
      aprikalim, and those of nicorandil, a dual-acting agent that increases cyclic
      guanosine monophosphate (cGMP) levels and opens K-ATP channels. These effects
      were compared with those of a pure NO donor, 3-morpholino-sydnonimine (Sin-1).
      Ventricular myocytes were isolated from the hearts of adult rats. Changes in
      cytosolic calcium concentration ([Ca2+]i) were measured by using a Ca2+
      indicator, indo-1/AM. Alterations in indo-1 fluorescence were recorded during
      regular electrical stimulation. After 10 min of pacing, end-diastolic [Ca2+]i was
      significantly increased as compared with control without significant changes in
      calcium transient. For doses of 10(-7) to 10(-4) M, aprikalim and nicorandil did
      not affect significantly the calcium transient. Sin-1 produced a significant
      decrease in calcium transient (by approximately 20%), which was already maximal
      at 10(-7) M. When given with the potassium channel antagonist glibenclamide (10(
      5) M), nicorandil induced the same effects as those observed with Sin-1. We
      conclude that potassium channel openers aprikalim and nicorandil do not not
      decrease calcium transient. Thus the NO-donor properties of nicorandil are not
      apparent when given alone but appear when ATP-dependent potassium channels are
      blocked.

PMID- 10069675
TI  - Effects of sodium nitroprusside on renal functions and NO-cGMP production in
      anesthetized dogs.
AB  - Although the renal nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) system
      plays an important role in maintaining urinary sodium and water excretion,
      effects of an authentic NO donor sodium nitroprusside (SNP) on urine formation
      have been controversial. In this study, we examined whether SNP increases renal
      NO release and cGMP production and induces natriuresis in the denervated kidney
      of anesthetized dogs. The intrarenal arterial infusion of SNP at 10, 30, and 100
      ng/kg/min did not affect renal function or NO-cGMP production. The higher dose of
      SNP (1,000 ng/kg/min) reduced systemic blood pressure and urine flow rate. The
      antidiuresis was observed also in the contralateral control kidney, the degree of
      which was larger than that observed in the ipsilateral SNP-infused kidney. During
      the SNP infusion, reductions in urinary Na+ excretion, fractional Na+ excretion,
      and urinary nitrite + nitrate excretion occurred in the control kidney but not in
      the SNP-infused kidney. Urinary cGMP excretion and renal venous plasma cGMP
      concentration were significantly increased during the SNP infusion in the SNP
      infused kidney but not in the control kidney. These renal effects of SNP were
      similar to those obtained by intrarenal arterial infusion of a specific NO donor,
      NOC 7 (300 ng/kg/min). These results suggest that SNP can produce nitric oxide
      and increase cGMP levels in the kidney and suppress sodium reabsorption, but the
      natriuretic property of SNP may be masked by its counteracting effects including
      the systemic hypotension in anesthetized dogs.

PMID- 10069676
TI  - Recovery of cardiac norepinephrine concentration and tyrosine hydroxylase
      activity by the central alpha2-adrenoceptor agonist guanabenz in rats with aortic
      constriction.
AB  - Depletion of cardiac norepinephrine has been reported in cardiac hypertrophy.
      This depletion causes less support for cardiac output in response to sympathetic
      nerve activation. The central nervous system is thought to be involved in this
      abnormality. Correction of this abnormality is expected to restore proper support
      for the heart. Clipping of the ascending aorta or a sham operation was performed
      in 10-week-old rats. At 4 weeks after the operation, the left ventricular
      norepinephrine concentration in clipped rats decreased (p<0.01). The clipped rats
      and sham-operated rats were treated with either guanabenz (1 mg/kg) or a vehicle
      for 4 weeks starting from fifth postoperative week. The level of left ventricular
      norepinephrine increased more in clipped rats treated with guanabenz (469+/-37
      ng/g) than in clipped rats treated with a vehicle (325+/-28 ng/g). The
      norepinephrine concentration in the left ventricle recovered significantly after
      the treatment with guanabenz (p<0.001). Tyrosine hydroxylase activity in the left
      ventricle also recovered after treatment with guanabenz (p<0.01). Modulation of
      sympathetic nerve tone by the alpha2-adrenoceptor agonist restored cardiac
      norepinephrine concentration and tyrosine hydroxylase activity. This could be a
      new approach to the treatment of heart failure.

PMID- 10069677
TI  - Enhancement of constrictor response of spastic coronary arteries to acetylcholine
      but not to phenylephrine in patients with coronary spastic angina.
AB  - This study examined the direct response of smooth muscle of coronary spasm sites
      to alpha1-adrenergic stimulation in patients with coronary spastic angina.
      Phenylephrine (1 microM in the coronary circulation, for 5 min), a stimulator of
      alpha1-adrenoreceptors, was directly infused into coronary arteries with spasm in
      10 patients with coronary spastic angina and into normal coronary arteries in 10
      control patients. The luminal diameter of epicardial coronary arteries was
      determined by computer-assisted quantitative angiography. The constrictor
      response to intracoronary injection of acetylcholine (ACh; 50 microg) was greater
      in spastic arteries than in control arteries (decrease from baseline, 48+/-2% vs.
      12+/-2%, respectively; p<0.001). ACh (50 or 100 microg) induced coronary spasm
      associated with myocardial ischemia in all of patients with coronary spastic
      angina but not in any control patients. On the other hand, phenylephrine infusion
      did not induce coronary spasm in any of patients with coronary spastic angina or
      in control subjects. The constrictor response to phenylephrine infusion was
      comparable between spasm and control coronary arteries (decrease from baseline,
      11+/-2% vs. 9+/-2%, respectively; p = NS). The results indicate that smooth
      muscle of spastic coronary arteries does not exhibit enhancement of constrictor
      response to direct stimulation of alpha1-adrenoreceptor on coronary smooth
      muscle. There may be receptor-specific enhancement of constrictor response to
      agonists in smooth muscle of spastic coronary arteries in patients with coronary
      spastic angina.

PMID- 10069678
TI  - Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin
      II in humans in vivo.
AB  - Angiotensin II is a powerful vasoconstrictor and proatherogenic factor. It was
      recently suggested that the endothelium may influence the actions of angiotensin
      II by production of, for example, nitric oxide and superoxide. By using venous
      occlusion plethysmography, forearm blood flow was measured in 26 healthy subjects
      during intraarterial cumulative infusion of angiotensin II. In 14 subjects, the
      interaction between angiotensin II and NO was studied by infusion of angiotensin
      II before and after clamping NO availability at a fixed basal level by using N(G)
      monomethyl-L-arginine (L-NMMA) and nitroprusside. During a "free" NO system,
      blood flow decreased on angiotensin II infusion from 2.70+/-0.30 ml/100 ml
      forearm/min to 1.38+/-0.15 ml/100 ml forearm/min, whereas during NO-clamp
      vasoconstriction was significantly enhanced (blood flow from 2.56+/-0.25 to
      1.19+/-0.13; p<0.05 saline vs. NO clamp). In 12 other subjects, the interaction
      between angiotensin II and superoxide was evaluated by comparison of the effects
      of angiotensin II before and after coinfusion of vitamin C. Angiotensin II
      induced vasoconstriction was significantly attenuated by vitamin C at higher
      dosages of angiotensin (saline, blood flow from 3.08+/-0.33 to 1.12+/-0.09;
      vitamin C, blood flow from 3.01+/-0.23 to 1.61+/-0.13; p<0.05 saline vs. vitamin
      C). Vitamin C had no effect on baseline forearm blood flow. In conclusion, this
      study demonstrates that the constrictor actions of angiotensin II are enhanced
      during NO clamp and attenuated during vitamin C, suggesting direct angiotensin II
      associated stimulation of endothelial NO and of oxygen radicals, respectively, in
      humans in vivo.

PMID- 10069679
TI  - Systemic and regional hemodynamics assessment in rats with fluorescent
      microspheres.
AB  - The aim of this study was to validate in rats an alternative to the radioactive
      microspheres (RM) reference technique, the fluorescent microspheres (FM), for the
      simultaneous determination of cardiac index (CI) and regional blood flows (RBF).
      Validation of the FM method was performed in three steps: (a) comparison of CI
      and RBF values obtained simultaneously by FM and RM, (b) determination of the
      repeatability of the measurements by using two successive injections of FM, and
      (c) evaluation of the ability of the FM method to assess vasodilating effects (by
      using dipyridamole). CI values (range, 242-513 ml/min x kg; n = 20) obtained with
      FM correlated with those obtained with RM (r = 0.82: p<0.001), and agreement was
      found between FM and RM (error 95% confidence interval for one pair, +/-125
      ml/min x kg). FM RBF values, although smaller than corresponding RM RBF values,
      were correlated with the latter (range, 0.1-7 ml/min x g; n = 71; r = 0.99; p<
      0.001). Agreement was dependent on RBF values, e.g., error 95% confidence
      intervals for one pair were 0.08-0.13 and 3.86-6.48 for 0.1 and 5 ml/min x g,
      respectively. Two successive FM injections at a 10-min interval (conscious rats)
      provided similar values (n = 14) for CI (306+/-24 vs. 346+/- 18 ml/min x kg), and
      renal (5.1+/-0.2 vs. 6.2+/-0.3 ml/min x g), left (6.1+/-0.3 vs. 5.8+/-0.4 ml/min
      x g) and right (4.8+/-0.4 vs. 4.7+/-0.3 ml/min x g) myocardial RBF. Corresponding
      error 95% confidence intervals were +/-187 ml/min x kg, +/-2.8, +/-2.2, and +/
      2.0 ml/min x g, respectively. Dipyridamole (2, 4, 6, and 8 mg/kg x min for 10
      min, i.v.; n = 9-13 per group, conscious rats) significantly and dose dependently
      increased left and right myocardial blood flows, whereas renal blood flow was not
      affected. We conclude that the FM technique (a) is reliable and in agreement with
      the RM method, (b) provides repeatable measurements of systemic and regional
      hemodynamics, and (c) allows detection and quantification of vasodilating effects
      in rats.

PMID- 10069680
TI  - Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular
      hypertrophy and improves diastolic function in the remodeling post-myocardial
      infarction ventricle.
AB  - To evaluate the role of angiotensin II (AII) on diastolic function during post
      myocardial infarction (MI) ventricular remodeling, coronary ligation or sham
      operation was performed in male Sprague-Dawley rats. Experimental animals were
      maintained on either irbesartan, a selective AT1-receptor antagonist, or no
      treatment. Measurement of cardiac hypertrophy, diastolic function, and
      sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA) and
      phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial
      infarction caused a significant increase in myocardial mass and left ventricular
      (LV) filling pressure, whereas LV systolic pressure and +dP/dt were reduced. The
      time constant of isovolumic relaxation (tau) was markedly prolonged after MI.
      Post-MI hypertrophy was associated with substantial increases in the messenger
      RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant
      changes in SERCA or PLB levels. Although irbesartan treatment did not
      significantly alter post-MI LV systolic or filling pressures, it nevertheless
      effectively decreased ventricular hypertrophy, improved tau, and normalized ANP
      expression. These results demonstrate that AT1-receptor antagonism has important
      effects on myocardial hypertrophy and ANP gene expression, which are independent
      of ventricular loading conditions. In addition, the improvement in diastolic
      function was not related to changes in SERCA and PLB gene expression, suggesting
      that enhanced myocardial relaxation was related to the blockade of AII effects on
      myocyte function or through a reduction of ventricular hypertrophy itself or
      both.

PMID- 10069681
TI  - Caffeine increases renal renin secretion in a rat model of genetic heart failure.
AB  - In a previous study, we showed that caffeine (CAFF) increases basal renin
      secretion by blocking intrarenal adenosine receptors and, when sympathetic
      activity is increased, augments renin release in part by blockade of brain
      adenosine receptors, leading to increased central sympathetic tone. The purpose
      of this study was to investigate the effects of CAFF treatment on neurohumoral
      status and heart performance in experimental heart failure. Two series of
      experiments were performed. First, the effects of CAFF (10 mg/kg +150 microg/min
      over 40 min) on heart performance (time-pressure variables) and neurohumoral
      status were studied in conscious, 9-month-old Wistar-Kyoto (WKY) rats,
      spontaneously hypertensive rats (SHRs), and spontaneously hypertensive heart
      failure (SHHF/Mcc-fa(cp) rats. Second, caffeine (0.1% in drinking water) was
      given for 10 days to 14-month-old SHHF/Mcc-fa(cp) rats, and cardiac performance,
      renal function, and neurohumoral status determined in vivo. CAFF infusion
      increased heart rate, left ventricular peak systolic pressure, and workload in
      hypertensive (SHRs and SHHF), but not in normotensive (WKY) animals and had no
      effects on cardiac contractility in all three strains. CAFF increased plasma
      renin activity (PRA), norepinephrine (NE), and epinephrine (E) levels in all
      three strains [treatment effect, p<0.001, 2F analysis of variance (ANOVA)], and
      these effects were greater in hypertensive (SHRs and SHHF) animals as compared
      with normotensive WKY rats (p<0.015). Ten-day CAFF treatment in 14-month-old SHHF
      did not change measured cardiac time-pressure variables, or hemodynamic or renal
      excretory function parameters that can affect renin secretion. However, CAFF
      treatment significantly increased renal renin secretion (71.1+/-19.2 vs. 9.5+/
      5.8 ng Ang I/h/min/kg for caffeine and control group, respectively; p<0.01). In
      summary, acute administration of CAFF increases workload, but has no effects on
      cardiac contractility in conscious SHHF rats. The cardiac effects are accompanied
      by increased renin release and NE and E plasma levels. Moreover, this study
      provides the first evidence that short-term caffeine consumption increases renal
      renin secretion in heart failure, an effect most likely due to the blockade of
      intrarenal adenosine receptors. It is possible that long-term activation of
      neurohumoral mechanisms by CAFF could have adverse effects in heart failure.

PMID- 10069682
TI  - Comparison of irbesartan with captopril effects on cardiac hypertrophy and gene
      expression in heart failure-prone male SHHF/Mcc-fa(cp) rats.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have proven an effective means to
      control hypertension and manage cardiac hypertrophy. It is presently unknown if
      newer specific angiotensin II subtype 1 receptor (AT1R) antagonists are as
      effective or more effective in treating these conditions compared with ACE
      inhibitors. There is evidence that these classes of drugs may affect cardiac
      hypertrophy by different mechanisms. This study compared the effect of
      irbesartan, an AT1R antagonist, with that of captopril, an ACE inhibitor, on
      expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc
      fa(cp) rats. SHHF/Mcc-fa(cp) rats (n = 10/group) were given captopril (100
      mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and
      captopril significantly reduced systolic pressure and produced similar rightward
      shifts in the angiotensin I dose-response curve. Renal renin gene expression was
      increased 8.6-fold by irbesartan and 17.7-fold by captopril. The only effect on
      echocardiographic findings was a similar decrease in aortic peak velocity, an
      index of systolic function, by both treatments. Early markers of cardiac
      hypertrophy were significantly attenuated by both drugs. Both drugs produced
      marked and equivalent reductions in left ventricular atrial natriuretic peptide
      (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP
      gene expression was accompanied by a decrease in plasma ANP concentration in the
      treatment groups. The shift from V1 to V3 myosin isozymes was similarly decreased
      in both treatment groups, compared with controls. These data suggest that
      captopril and irbesartan are similarly effective in controlling expression of
      genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc
      fa(cp) rat.

PMID- 10069683
TI  - Cardiac effects of beta-adrenoceptor antagonists with intrinsic sympathomimetic
      activity in humans: beta1- and/or beta2-adrenoceptor mediated?
AB  - The aim of this study was to find out whether cardiac responses to the beta
      adrenoceptor antagonists with intrinsic sympathomimetic activity (ISA) xamoterol
      and celiprolol are mediated by cardiac beta1- or beta2-adrenoceptors or both. For
      this purpose we assessed, in six healthy male volunteers, the effects of
      xamoterol (100 and 200 mg, p.o.) and celiprolol (200, 600, and 1,200 mg, p.o.) on
      blood pressure, heart rate, and heart rate-corrected duration of the
      electromechanical systole (QS2c, as a measure of inotropism). Xamoterol, in both
      doses, increased systolic blood pressure and heart rate, transiently decreased
      diastolic blood pressure, and shortened QS2c; all these effects were attenuated
      after pretreatment of the volunteers with the beta1-adrenoceptor antagonist
      bisoprolol. Celiprolol, in all three doses, increased heart rate, decreased
      diastolic blood pressure, and shortened QS2c but only marginally increased
      systolic blood pressure. Bisoprolol did not attenuate these celiprolol effects
      but rather enhanced celiprolol effects on systolic blood pressure and heart rate.
      In a further set of experiments, we studied cardiovascular effects of celiprolol
      in six healthy volunteers whose beta2-adrenoceptors had been desensitized by a 2
      week treatment with 3x5 mg/day terbutaline. Under these conditions, celiprolol
      failed to increase heart rate or to shorten QS2c. We conclude that, under resting
      conditions, in healthy volunteers, beta-adrenoceptor antagonists with ISA can
      exert increases in heart rate and contractility that are mediated by either
      cardiac beta1-adrenoceptor (xamoterol) or cardiac beta2-adrenoceptor (celiprolol)
      stimulation. Thus in the human heart, the ISA of beta-adrenoceptor antagonists
      can be a beta1- or beta2-adrenoceptor agonistic component.

PMID- 10069684
TI  - Effects of lipid-lowering drugs on left ventricular function and exercise
      tolerance in dyslipidemic coronary patients.
AB  - Previous studies suggested that certain lipid-lowering drugs such as statins
      suppress ubiquinone, affect mitochondrial function, and may have deleterious
      effect on skeletal or cardiac muscles with potentially serious clinical
      consequences, especially in patients with established coronary heart disease and
      left ventricular dysfunction. In this double-blind study, we assessed the effects
      of 20 mg simvastatin (S, n = 32) or 200 mg micronized fenofibrate (F, n = 32,
      control group) on rest and exercise left ventricular function in
      hypercholesterolemic survivors of a previous Q-wave acute myocardial infarction.
      Left ventricular radionuclide imaging was performed at rest and during submaximal
      exercise and global and segmental (nine segment regional wall-motion score)
      ejection fractions were measured before treatment and 12 weeks later. Serum
      ubiquinone was reduced after treatment (p = 0.03) in the S but not the F group,
      whereas total and low-density lipoprotein (LDL) cholesterol were significantly
      reduced in both groups. Before treatment, mean global ejection fraction was
      52.1+/-12.2% and 49.3+/-11.8% at rest in F and S patients, respectively, and
      increased (56.0+/-13.7% in F and 52.1+/-12.9% in S) at peak exercise (no
      difference between groups). After treatment, the increase in ejection fraction
      tended to be lower in S (0) than in F (+3.8%) but not significantly. However,
      ejection fraction at rest increased after treatment in S (p = 0.009) but not in
      F. Subgroup analyses indicated that the improvement in rest ejection fraction in
      S was essentially observed in patients with ejection fraction <40% (n = 8, +6%),
      whereas it was stable in patients with ejection fraction >40% (+1.8%). Finally,
      the numbers of akinetic or hypokinetic segments at rest and during exercise were
      not different in the two groups before and after treatment. Mean maximal exercise
      load (113+/-23 watts in F vs. 104+/-27 W in S before treatment) was not modified
      by the treatment (111+/-21 and 104+/-27 W). Thus a 12-week lipid-lowering
      treatment with either S or F did not negatively alter left ventricular function
      during exercise in dyslipidemic patients with established coronary heart disease
      and did not affect their ability to exercise. The improvement in left ventricular
      function at rest after simvastatin in patients with left ventricular dysfunction
      warrants confirmation in further studies with large sample size.

PMID- 10069685
TI  - Long-acting lacidipine versus short-acting nifedipine in the treatment of
      asymptomatic acute blood pressure increase.
AB  - We compared antihypertensive efficacy and safety of a single administration of
      equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies.
      Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women)
      with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure
      (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs
      for the last 24 h, were randomized in a single-blind fashion to receive
      lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14
      patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken
      every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline
      BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs.
      NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant
      reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg)
      and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h.
      However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP
      (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the
      NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in
      BP >25% of the baseline value both 8 and 24 h after the dose. Although 10
      patients showed the same response in the NFD group 8 h after the dose, only four
      patients maintained these values at 24 h. One patient treated with NFD had a
      transient cerebrovascular ischemic attack. No adverse effects were observed in
      the LCD group. We conclude that the long-acting calcium antagonist lacidipine was
      more effective than the short-acting nifedipine in both controlling BP and
      maintaining this BP reduction over 8 h in essential hypertensive patients with
      acute asymptomatic BP increase.

PMID- 10069686
TI  - Lacidipine prevents the hypertension and renal and cardiac changes induced by
      high-fructose diet in WKY rats.
AB  - Normotensive rats fed a high-fructose diet (HFD) develop hypertriglyceridemia,
      hyperinsulinemia, and hypertension. The glomerular changes observed in the
      kidneys of these animals are similar to those observed in diabetic rats. The aim
      of this study was to evaluate whether lacidipine, a calcium antagonist, could
      have a protective effect with this animal model. Forty male Wistar-Kyoto (WKY)
      rats were divided into four groups treated with HFD + placebo; HFD + lacidipine,
      0.3 mg/kg/day; HFD + lacidipine, 3 mg/kg/day; or standard diet + placebo for 4
      weeks. Urinary excretion of the stable metabolic products of nitric oxide (NO)
      was determined, because this vasoactive agent has been found to cause hemodynamic
      changes in the diabetic kidney. Glomerular size was determined by means of
      morphometric analysis. The results of this study show that lacidipine prevents
      (a) the HFD-induced increase in blood pressure in a dose-dependent manner; (b)
      the HFD-induced increase in glomerular size and fibronectin synthesis; and (c)
      the increase of collagen III synthesis in the heart. The drug had no effect on
      the increased urinary excretion of the stable metabolic products of NO. These
      data suggest that lacidipine might be useful in preventing the renal and cardiac
      damage caused by hypertension and non-insulin-dependent diabetes mellitus.

PMID- 10069687
TI  - Effect of bepridil on intracellular calcium concentration and contraction in
      cultured rat ventricular myocytes.
AB  - We studied the effects of a new antiarrhythmic and antianginal agent, bepridil,
      on the intracellular calcium transient and contraction of cultured neonatal rat
      ventricular cells, and compared the effects with those caused by an authentic
      Ca2+ -entry blocker, D600 (methoxyverapamil). The Ca2+ transient was measured by
      using dual-wavelength microfluorometry of fura-2. The contraction was measured as
      a shortening of cell aggregates with the use of a video image-analyzing system.
      Both bepridil (1-30 microM) and D600 (1-30 microM) decreased the peak systolic
      amplitude of the Ca2+ transient in a concentration- and frequency-dependent
      manner. Bepridil, but not D600, significantly shortened the half-decay time of
      the Ca2+ transient and prolonged the time course of the contraction. D600
      decreased the contraction in parallel with the decrease in the peak Ca2+
      transient, whereas bepridil exerted no significant effect on the contraction.
      Bepridil (10 microM) induced a leftward shift (to lower amplitude of peak
      systolic Ca2+ transient) of the relation between the magnitude of contraction and
      the peak systolic Ca2+ transient, which was obtained by changing external Ca2+
      concentration. In contrast, D600 (10 microM) did not affect the relation. The
      results suggest that the negative inotropic effect of bepridil (caused by its
      Ca2+ channel-blocking effect) is offset by its simultaneous increase in the
      sensitivity of contractile protein(s) to intracellular Ca2+, which may be a
      unique characteristic of this antiarrhythmic agent in a clinical setting.

PMID- 10069688
TI  - Trimetazidine: potential mechanisms of action in hypertrophic cardiomyopathy.
AB  - In this review we consider available information on the cardio- and
      cytoprotective properties and mechanism of action of trimetazidine, an
      antianginal drug. Two points in particular are addressed: the advantages of
      trimetazidine over classic drugs and its possible use for the long-term treatment
      of hypertrophic cardiomyopathy, described as an ischemic disorder.

PMID- 10069689
TI  - Terfenadine block of sodium current in canine atrial myocytes.
AB  - Terfenadine, a histamine-1 receptor antagonist, is known to have direct effects
      on electrical activities in the heart. Studies have demonstrated an ability of
      terfenadine to suppress upstroke velocity of action potential, an indication of
      sodium channel blockade. To clarify whether terfenadine indeed blocks sodium
      current (I(Na)), we performed experiments to evaluate in detail the effects of
      terfenadine on I(Na) by applying whole-cell patch-clamp techniques to canine
      atrial myocytes. Terfenadine produced concentration-dependent inhibition of
      I(Na), with a median inhibitory concentration (IC50) of 0.93+/-0.12 microM.
      Significant effects were observed at a concentration of as low as 100 nM
      (approximately 15% reduction of I(Na)). The effects of terfenadine on I(Na) were
      voltage dependent, as indicated with greater inhibition at less-negative holding
      potentials and at more-positive test potentials. Terfenadine blockade of I(Na)
      was characterized by an important tonic block that accounted for approximately
      50% of the total block. Use-dependent block also was observed and found to
      contribute to 26% of the total block, and this use dependence was accentuated
      with longer pulse duration. Our findings suggest that terfenadine is a potent
      sodium channel blocker. Terfenadine blocks I(Na) in both rested state and
      inactivated state of the channels, but preferentially interacts with the former.
      The I(Na)-blocking property of terfenadine may contribute to its cardiac side
      effects in patients.

PMID- 10069690
TI  - Translocation of MAP (Erk-1 and -2) kinases to cell nuclei and activation of c
      fos gene during healing of experimental gastric ulcers.
AB  - We examined localization of extracellular signal regulated kinases (Erk) 1 and 2,
      and c-fos mRNA expression in normal and ulcerated gastric mucosa in rats at 1, 3
      and 7 days after gastric ulcer induction. In normal gastric mucosa
      immunofluorescence signal for Erk-1 and Erk-2 was detectable in surface
      epithelial, neck and some glandular cells. In gastric mucosa of the ulcer margin,
      almost all epithelial cells displayed strong Erk-1 and Erk-2 immunoreactivity in
      the basolateral membranes and the cytoplasm. In addition 19+/-3% of cells showed
      nuclear localization of the Erk-1 and -2 signal. The c-fos mRNA expression was
      increased by 790+/-14% and 220+/-10%, respectively in gastric ulcer at 3 and 7
      days after ulcer induction. Since in in vitro models nuclear translocation of Erk
      1 and -2 triggers cell proliferation, our finding indicates relevance of this
      mechanism to gastric ulcer healing.

PMID- 10069691
TI  - Role of basic fibroblast growth factor in the suppression of apoptotic caspase-3
      during chronic gastric ulcer healing.
AB  - BACKGROUND: In the course of ulcer healing an array of factors compel mucosal
      cells to proliferate, differentiate, and migrate to the site of injury. The
      recognition of triggering cues requires close interaction between the regulatory
      proteins integrating the growth factor and cytokine- mediated signals that propel
      cells through the cycle events, or to signal apoptosis. In this study, we
      analyzed the interplay between mucosal expression of the receptor-bound basic
      fibroblast growth factor (bFGF-R) and cyclin-dependent kinase (Cdk2), and the
      activity of apoptotic protease, caspase-3, and constitutive nitric oxide synthase
      (cNOS) during chronic gastric ulcer healing. METHODS: The experiments were
      conducted with gastric mucosa of rats at different stages of acetic acid-induced
      chronic gastric ulcer healing. RESULTS: The ulcer onset (2 days following injury)
      was characterized by a massive epithelial apoptosis associated with a 33-fold
      increase in caspase-3 activity and a 7.6-fold drop in cNOS, while the mucosal
      expression of Cdk2 fell by an 18% and that of bFGF-R by 12%. The ulcer healing
      was accompanied by a rapid elevation in bFGF-R and Cdk2, and a slow recovery in
      cNOS activity, while the caspase-3 activity and epithelial apoptosis showed a
      marked decline. The bFGF-R and Cdk2 reached their maximums of 2.2-2.3-fold at 4-6
      day of healing, while the caspase-3 activity and the apoptotic DNA fragmentation
      showed a 3-fold decline by the 7th day of healing. However, the activity of cNOS
      remained about 50% lower than that of the controls. CONCLUSIONS: Taken together,
      these results provide strong indications that the initial phase of ulcer healing
      involves the inhibition of apoptotic caspase activities by a signaling events
      initiated by bFGF-receptor activation and propagated by the regulatory kinases
      that propel the cell cycle progression. Our findings also point towards
      participation of cNOS in the suppression of proapoptotic activities in gastric
      mucosa.

PMID- 10069692
TI  - Cyclooxygenase-2 selective and nitric oxide-releasing nonsteroidal anti
      inflammatory drugs and gastric mucosal responses.
AB  - Occurrence of gastrointestinal damage and delayed healing of pre-existing ulcer
      are commonly observed in association with clinical use of nonsteroidal
      antiinflammatory drugs (NSAIDs). We examined the effects of NS-398, the
      cyclooxygenase (COX)-2 selective inhibitor, and nitric oxide (NO)- releasing
      aspirin (NCX-4016) on gastric mucosal ulcerogenic and healing responses in
      experimental animals, in comparison with those of nonselective COX inhibitors
      such as indomethacin and aspirin. Indomethacin and aspirin given orally were
      ulcerogenic by themselves in rat stomachs, while either NS-398 or NCX-4016 was
      not ulcerogenic at the doses which exert the equipotent antiinflammatory action
      with indomethacin or aspirin. Among these NSAIDs, only NCX-4016 showed a dose
      dependent protection against gastric lesions induced by HCl/ethanol in rats. On
      the other hand, the healing of gastric ulcers induced in mice by thermal
      cauterization was significantly delayed by repeated administration of these
      NSAIDs for more than 7 days, except NCX-4016. Gastric mucosal prostaglandin
      contents were reduced by indomethacin, aspirin and NCX-4016 in both normal and
      ulcerated mucosa, while NS-398 significantly decreased prostaglandin generation
      only in the ulcerated mucosa. Oral administration of NCX-4016 in pylorus-ligated
      rats and mice increased the levels of NO metabolites in the gastric contents. In
      addition, both NS-398 and NCX-4016 showed an equipotent anti-inflammatory effect
      against carrageenan-induced paw edema in rats as compared with indomethacin and
      aspirin. These results suggest that both indomethacin and aspirin are ulcerogenic
      by themselves and impair the healing of pre-existing gastric ulcers as well. The
      former action is due to inhibition of COX-1, while the latter effect may be
      accounted for by inhibition of COX-2 and mimicked by NS-398, the COX-2 selective
      NSAID. NCX-4016, despite inhibiting both COX-1 and COX-2, protects the stomach
      against damage and preserves the healing response of gastric ulcers, probably
      because of the beneficial action of NO.

PMID- 10069693
TI  - Relationship between vascular endothelial growth factor and angiogenesis in
      spontaneous and indomethacin-delayed healing of acetic acid-induced gastric
      ulcers in rats.
AB  - Angiogenesis is an important event for gastric ulcer healing. Vascular
      endothelial growth factor (VEGF) is known to be a potent stimulator of
      angiogenesis. This study consequently examined VEGF production, VEGF mRNA
      expression and angiogenesis during the spontaneous and indomethacin-delayed
      healing of acetic acid-induced ulcers in rats. The production of VEGF, taking
      place in the normal mucosa, was significantly elevated by ulceration. The mRNA
      expression of three isoforms of VEGF (VEGF188, VEGF164 and VEGF120) was also
      detected. Following the increase in VEGF production, angiogenesis was
      significantly promoted in the ulcer base. VEGF-immunoreactivity was observed in
      granulocytes, fibroblasts and regenerated epithelial cells. Indomethacin markedly
      inhibited prostaglandin E2 synthesis in the ulcer base, resulting in the
      prevention of ulcer healing. Angiogenesis was also significantly inhibited by
      indomethacin, but neither VEGF production nor VEGF mRNA expression was reduced.
      Such results suggest that VEGF might play a role in angiogenesis in the
      spontaneous healing of gastric ulcers in rats. However, the inhibition of
      angiogenesis in indomethacin-delayed ulcer healing is not explainable on VEGF
      expression.

PMID- 10069694
TI  - Disturbed gastric motility and pancreatic hormone release in diabetes mellitus.
AB  - BACKGROUND AND AIMS: The influence of glucose metabolism and postprandial release
      of glucagon on gastric emptying in diabetes mellitus is still unclear. The aim of
      this study was to assess the relationship between glucose, insulin and glucagon
      and alterations of gastric motility in symptomatic diabetic subjects with delayed
      gastric emptying. METHODS: Scintigraphy for solids and liquids, 13C-acetate
      breath test, electrogastrography and antral manometry were assessed in 20
      symptomatic subjects with diabetes mellitus type II and in 20 healthy controls.
      Simultaneously, serum glucose, glucagon and insulin levels were determined during
      the functional studies. RESULTS: Postprandial increase in antral motility and
      myoelectrical activity were seen in controls, but were missing in the group with
      diabetes mellitus. Moreover, in the fasting state the dominant frequency
      instability coefficient observed in healthy individuals and in subjects with
      diabetes of short (<5 years) duration was significantly reduced in subjects with
      longer duration of diabetes while the postprandial increase in dominant frequency
      instability coefficient was missing in all diabetics. Following the standard test
      meal, serum glucose and plasma glucagon in the diabetics increased to a
      significantly higher degree when compared to controls. CONCLUSIONS: Symptomatic
      subjects with delayed gastric emptying present abnormal patterns of gastric motor
      and electrical activity. Higher than normal postprandial plasma levels of
      glucagon may, at least in part, be responsible for disturbed gastric motility in
      non-insulin-dependent diabetic subjects.

PMID- 10069695
TI  - Myoelectric bowel activity in ischemia/reperfusion damage. Role of sensory
      neurons.
AB  - The present knowledge indicates that afferent sensory neurons (C-fibres) play an
      important role in the relationship between intestinal myoelectric activity (IMA)
      and blood flow (LDBF). The aim of this study was to evaluate the role of C-fibers
      in myoelectric activity of small intestine during its ischemia and reperfusion. A
      neurotoxin-capsaicin (CAP) was used to induce functional ablation of afferent
      sensory neurons. Experiments were performed on 6 groups of anesthetized rats. In
      the I, II, III group of rats IMA and LDBF were recorded during 100% ischemia
      induced by AMA 15, 30 and 60 min total occlusion and during 60 min reperfusion
      period. In group V and VI, IMA and LDBF were registered after intrajejunal
      placement of 1% CAP. In group IV we measured effects of intraluminal instillation
      of CAP alone. Intraluminal placement of CAP induced an early increase in slow
      wave amplitude SWA and slow wave frequency SWF by 35+/-11% and 19+/-10% (p<0.05)
      with the subsequent decrease in both by 25+/-6 and 24+/-8% (p<0.05) respectively.
      Short 15 min lasting ischemia induced by 100% occlusion of AMA evoked only a
      slight increase of SWA. During reperfusion period SWA and SWF returned to the
      baseline values after 15 min. Total 30 min occlusion decreased SWA and SWF by
      25+/-9 and 24+/-6% (p<0.05) respectively. During reperfusion period recovery of
      IMA parameters to preocclusion values were slower. Intestinal hyperemia was
      smaller than in previous group. After 60 min lasting intestinal ischemia SWA and
      SWF were decreased by 58+/-7 and 40+/-6% (p<0.01) respectively. There was no
      return of IMA parameters to control values. These data demonstrated that
      intestinal ischemia induces typical changes in the bowel myoelectric activity.
      These changes possess their own electrical characteristics which can be used in
      clinical practice for evaluation of the degree ischemically-induced intestinal
      injury. Capsaicin pretreatment significantly decreased SWA and SWF and LDBF in
      comparison with those observed in group II and III during 30 and 60 min occlusion
      and reperfusion period. We conclude that afferent neurons C activated during
      mesenteric ischemia/reperfusion play an important role in protecting ischemic
      bowel viability.

PMID- 10069696
TI  - Adrenal-renal portal circulation contributes to decrease in renal blood flow
      after renal artery stenosis in rats.
AB  - The aim of the present study was to investigate a role of adrenal-renal portal
      circulation (ARPC) in a decrease in renal blood flow due to acute stenosis of the
      renal artery in rats. Animals were divided into three groups. In the control
      group (I), in order to eliminate the ARPC tissue between the adrenal gland and
      the ipsilateral kidney was cut. In the second and the third group (II) (III),
      left renal artery was stenosed by a silver clip (ID 0.40 mm). Then, in the group
      II, ARPC was surgically eliminated. In the group II, prior to the elimination of
      ARPC, alpha-adrenergic receptors blockade was produced by phentolamine
      administration. In the control group, ARPC elimination did not influence either
      renal blood flow (RBF) or renal vascular resistance (RVR). In the group II,
      elimination of ARPC caused increase in RBF and decrease in RVR In the group III
      elimination of ARPC influenced neither RBF nor renal vascular resistance (RVR).
      Results of the present study provide the functional evidence that catecholamines
      reaching the kidney through ARPC, contribute to the decrease in RBF and increase
      in RVR during acute renal artery stenosis in the rat.

PMID- 10069697
TI  - Increase in vasopressin concentration and cardiodepressant activity in the blood
      dialysates after NMDA and hypertonic saline administration.
AB  - It has been demonstrated that electric stimulation of the central ends of cut
      vagus nerves or angiotensin II infusion cause an increase in vasopressin
      concentration and cardiodepressant activity in the sella turcica venous blood.
      The present study was an attempt to determine if the cardiodepressant factor and
      vasopressin were simultaneously released from the pituitary into the blood
      dialysate after osmotic stimulation, and whether excitatory amino acids are
      involved in this mechanism. The samples of dialysates of venous blood flowing
      from the sella turcica region and, for comparison, from the femoral vein were
      collected in anaesthetised rats. The concentration of vasopressin in blood
      dialysate was determined by radioimmunoassay, and cardiodepressant activity on
      spontaneously discharging pacemaker tissue of the right auricle of the right
      heart atrium. Osmotic stimulation or N-methyl-D-aspartic acid infusion caused an
      increase in cardiodepressant activity and vasopressin concentration in the blood
      dialysate from the sella turcica and from the femoral vein. A blockade of the
      excitatory amino acids receptors by specific and non-specific antagonists
      significantly inhibited the increase in the blood dialysate vasopressin
      concentration and cardiodepressant activity elicited by an intra-arterial
      injection of hypertonic saline. These data indicate that excitatory amino acids
      are involved in the mechanism of increase in blood vasopressin and
      cardiodepressant factor concentration in response to osmotic stimulation. These
      results also demonstrate the utility of blood minidialysis for simultaneous
      monitoring of active substances concentration in the blood.

PMID- 10069698
TI  - Effects of mibefradil, a blocker of T-type Ca2+ channels, in single myocytes and
      intact muscle of guinea-pig heart.
AB  - We investigated the effects of a relatively selective blocker of the T-type Ca2+
      channels, mibefradil (MBF), in the isovolumic left ventricles of the isolated,
      perfused hearts of guinea-pigs and single myocytes isolated from the ventricles
      of this species. In the myocytes superfused with 0 Na+ solution containing 200
      microM lidocaine and pulsed from -90 mV to -40 mV to +5 mV, MBF proved to be
      about 3 times more potent inhibitor of the T-type than of the L-type Ca2+
      current. The effect on the L-type current was strongly voltage and use dependent.
      In the ventricles and in the myocytes contraction was reduced by 50% by about 1
      microM MBF, the concentration 12 times higher than this increasing the coronary
      flow by 50%. In myocytes the decrease in unloaded shortening paralleled
      inhibition of the T-type rather, than of the L-type Ca2+ current. Inhibition of
      electrically stimulated contraction of the myocytes was three times stronger than
      inhibition of the caffeine contractures regarded as an index of sarcoplasmic
      reticulum (SR) Ca2+ content. These findings are consistent with the hypothesis
      that the T-type Ca2+ channels may contribute to release of Ca2+ from the SR. It
      is concluded that MBF has a definite negative inotropic effect in the ventricular
      myocardium of guinea-pig heart at the concentrations found in the blood of the
      patients submitted to the clinical trials.

PMID- 10069699
TI  - Effect of a short-term dietary creatine supplementation on high-energy phosphates
      in the rat myocardium.
AB  - The aim of this study was to find out whether creatine (Cr) feeding affects total
      creatine (TCr), phosphocreatine (PCr), adenine nucleotide contents and beta
      hydroxy-acyl-CoA-dehydrogenase (HAD) activity in myocardium as compared to red
      skeletal muscle. Ten adult Wistar rats received Cr (2.5% of diet weight) for 7
      days. In Cr fed rats, PCr was increased (by approx. 20%) in cardiac and in soleus
      muscles with ATP elevated in myocardium and TCr and free Cr in soleus. In both
      muscles, Cr feeding enhanced HAD activity. It is concluded, that dietary Cr does
      increase cardiac muscle high energy phosphate reserves and its oxidative
      potential.

PMID- 10069700
TI  - The rate of changes in tension within fused tetani of single motor units in rat
      medial gastrocnemius muscle.
AB  - The time course of fused tetani of three main types of motor units: slow (S),
      fast resistant (FR) and fast fatigable (FF) was studied in the rat medial
      gastrocnemius. The rate of tension generation and of the relaxation within a
      tetanus was measured under isometric conditions. These measurements were
      performed at three points during both the contraction and relaxation: the
      beginning, the middle and the end of the phase of changes in tension. Significant
      differences were found in the rate of tension changes between fast and slow
      units. Comparison of FF and FR units showed less pronounced differences in their
      rates of the contraction and the relaxation. Moreover, slow units showed
      significantly greater slowing of both the contraction and relaxation within a
      tetanus in relation to the speed of their twitch when compared to fast motor
      units. The rate of changes in tetanic tension correlated to twitch time
      parameters and to tension generated during twitch or tetanus. The results point
      out that the well known difference in the speed of twitch contraction between
      fast and slow units is also visible in their fused tetani.

PMID- 10069701
TI  - Effect of L-NAME, a specific nitric oxide synthase inhibitor, on corticotropin
      releasing hormone-elicited ACTH and corticosterone secretion.
AB  - This study was designed to determine the role of endogenous nitric oxide (NO) in
      the corticotropin-releasing hormone (CRH)-induced ACTH and corticosterone
      secretion, as well as possible involvement of hypothalamic dopamine and
      noradrenaline in that secretion in conscious rats. CRH given i.p. stimulated dose
      dependently the pituitary-adrenocortical activity measured 1 h later.
      Dexamethasone (0.2 mg/kg i.p.) injected 1 h before CRH (1 microg/kg i.p.) totally
      abolished the CRH-elicited ACTH and corticosterone secretion, indicating a
      predominantly pituitary site of CRH-evoked stimulation. L-arginine (120 mg/kg
      i.p.) and N(omega)-nitro-L-arginine methyl ester (L-NAME 5-10 mg/kg i.p.) did not
      markedly affect the basal plasma ACTH and corticosterone levels. L-NAME given 15
      min before CRH markedly, but not significantly, augmented the CRH-induced ACTH
      response, and enhanced more potently and significantly the corticosterone
      response. Pretreatment with L-arginine, a substrate for NOS, slightly diminished
      the CRH-induced ACTH response and considerably reduced the corticosterone
      response. L-arginine also significantly reversed the L-NAME-evoked increase in
      the CRH-induced ACTH and corticosterone secretion. L-NAME did not markedly alter
      the CRH-induced hypothalamic dopamine and noradrenaline levels, while L-arginine
      significantly increased noradrenaline level. However, those alterations were not
      directly correlated with the observed changes in ACTH and corticosterone
      secretion. These results indicate that in conscious rats NO plays a marked
      inhibitory role in the CRH-induced ACTH secretion and inhibits more potently
      corticosterone secretion. Hypothalamic dopamine and noradrenaline do not seem to
      be directly involved in the observed alterations in ACTH and corticosterone
      secretion.

PMID- 10069702
TI  - Influence of nitric oxide synthase inhibitors on the vasopressin-induced
      pituitary-adrenocortical activity and hypothalamic catecholamine levels.
AB  - In the present study the role of endogenous nitric oxide (NO) in the vasopressin
      induced ACTH and corticosterone secretion was investigated in conscious rats.
      Vasopressin (AVP 5 microg/kg i.p.) considerably augmented ACTH and corticosterone
      secretion. L-arginine (120 and 300 mg/kg i.p.) did not significantly alter the
      AVP-induced secretion of those hormones. Nitric oxide synthase (NOS) blockers
      N(omega)-nitro-L-arginine (L-NNA) and its methyl ester (L-NAME) given i.p. 15 min
      before AVP markedly increased the AVP-induced ACTH secretion. L-NNA (2 mg/kg)
      more potently and significantly increased the AVP-induced ACTH secretion, whereas
      L-NAME elicited a weaker and not significant effect. Both those NOS antagonists
      intensified significantly and to a similar extent the AVP-induced corticosterone
      secretion. L-arginine (120 mg/kg i.p.) reversed the L-NNA-induced rise in the AVP
      stimulated ACTH secretion and substantially diminished the accompanying
      corticosterone secretion. Neither vasopressin alone nor in combination with L
      arginine and L-NAME evoked any significant alterations in the hypothalamic
      noradrenaline and dopamine levels. L-NNA (2 and 10 mg/kg i.p.) elicited a dose
      dependent and significant decrease in the hypothalamic noradrenaline level. The
      hypothalamic dopamine level was not significantly altered by any treatment. These
      results indicate that in conscious rats endogenous NO has an inhibitory influence
      on the AVP-induced increase in ACTH and corticosterone secretion. L-NNA is
      significantly more potent than L-NAME in increasing the AVP-induced ACTH
      secretion. This may be connected with a considerable increase by L-NNA of
      hypothalamic noradrenergic system activation which stimulates the pituitary
      adrenal axis in addition to specific inhibition of NOS.

PMID- 10069703
TI  - Biphasic effect of protein kinase C on rat renal cortical Na+, K+-ATPase.
AB  - We examined the dependence of rat renal Na+, K+-ATPase activity on protein kinase
      C (PKC) stimulation. Infusion of either phorbol 12, 13-dibutyrate (PDBu) or
      phorbol 12-myristate 13-acetate (PMA) into rat abdominal aorta resulted in dose
      dependent changes of renal cortical Na+, K+-ATPase activity. Low doses of these
      esters (3 x 10(-11) mol/kg/min) increased activity of Na+, K+-ATPase whereas high
      doses (3 x 10(-9) mol/kg/min) decreased it. The changes in Na+, K+-ATPase
      activity induced by PDBu and PMA were prevented by staurosporine, a PKC
      inhibitor. 4Alpha phorbol didecanoate (4alpha PDD), phorbol ester which does not
      activate PKC had no effect on cortical Na+, K+-ATPase. PDBu and PMA did not
      change Na+, K+-ATPase activity in the renal medulla. The stimulatory effect of
      PDBu (3 x 10(-11) mol/kg/min) was neither mimicked by amphotericin B, a sodium
      ionophore nor blocked by amiloride, an inhibitor of Na+/H+-exchanger. The
      inhibitory effect of 3 x 10(-9) mol/kg/min PDBu was not mimicked by amiloride
      indicating that the observed effects of PKC stimulation are not secondary to
      alterations in intracellular sodium concentration. The inhibitory effect of PDBu
      was prevented by infusion of ethoxyresorufin, an inhibitor of cytochrome P450
      dependent arachidonate metabolism. These results suggest that the inhibitory
      effect of PKC on renal cortical Na+, K+-ATPase is mediated by cytochrome P450
      dependent arachidonate metabolites.

PMID- 10069704
TI  - Aphallia as part of urorectal septum malformation sequence in an infant of a
      diabetic mother.
AB  - A male patient with aphallia, anal stenosis, tetralogy of Fallot, multiple
      vertebral anomalies including sacral agenesis and central nervous system (CNS)
      malformations was born after a pregnancy complicated by poorly controlled
      maternal diabetes. Aphallia is an extremely rare abnormality and can be part of
      the urorectal septum malformation sequence (URSMS). While aphallia has not been
      reported in infants of diabetic mothers, urogenital malformations are known to
      occur with increased frequency. Two female products of pregnancies complicated by
      diabetes presented with multiple malformations including anal atresia and recto
      vaginal fistula consistent with the diagnosis of URSMS. The three patients share
      CNS, cardiac, and vertebral anomalies, abnormalities secondary to abnormal
      blastogenesis and characteristic of diabetic embryopathy. URSMS is also caused by
      abnormal blastogenesis. Therefore, this particular malformation should be viewed
      in the context of the multiple blastogenetic abnormalities in the cases reported
      here. The overlap of findings of URSMS in our cases with other abnormalities of
      blastogenesis, such as VATER association or sacral agenesis is not surprising, as
      these associations are known to lack clear diagnostic boundaries.

PMID- 10069705
TI  - Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack of loss
      of heterozygosity in a lung cyst.
AB  - A Japanese patient with tuberous sclerosis (TSC), who manifested with multiple
      lung cysts and pneumothorax, is described. All exons of two TSC genes, TSC1 and
      TSC2, in peripheral blood leukocytes from the patient were analyzed by polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP). A novel T-to-G
      transition was found in exon 19 of TSC2 at nucleotide position 2168. This
      mutation caused an amino acid change, L717R. There was no such mutation in any
      other family members or in 100 normal Japanese. An automated sequencer-assisted
      quantitative analysis of normal and mutated SSCP-bands revealed no loss of
      heterozygosity (LOH) in the lung cyst tissue of the patient.

PMID- 10069706
TI  - "Tandem" duplication of 4p16.1p16.3 chromosome region associated with 4p16.3pter
      molecular deletion resulting in Wolf-Hirschhorn syndrome phenotype.
AB  - Chromosome imbalance affecting the short arm of chromosome 4 results in a variety
      of distinct clinical conditions. Most of them share a number of manifestations,
      such as mental retardation, microcephaly, pre- and post-natal growth retardation,
      anteverted and low-set ears, that can be considered as nonspecific signs,
      generally attributable to gene dosage impairment. On the other hand, more
      distinctive phenotypic traits correlate with the segmental aneuploidy.
      Duplications of the distal half of 4p give rise to the partial trisomy 4
      syndrome, characterized by a "boxer" nose configuration and deep-set eyes. These
      signs are usually observed even in cases of small terminal duplications.
      Haploinsufficiency of 4p16.3 results in the so-called Wolf-Hirschhorn (WH)
      syndrome, a contiguous gene syndrome characterized by maxillary hypoplasia, large
      and protruding eyes, high nasal bridge, skeletal abnormalities, and midline
      defects. The smallest overlapping deletion described so far as a cause of this
      condition is only 165 kb long, suggesting that one or a few genes in this region
      act as "master" regulators of different developmental pathways. A "tandem"
      duplication of 4p16.1p16.3 was detected in association with a subtle deletion of
      4p16.3pter on the same chromosome in a patient with the WH phenotype. The 3.2 Mb
      deletion, spanning the genomic region from the vicinity of D4S43 to the telomere,
      encompasses the recently delimited "WHS critical region" [Wright et al., 1997:
      Hum. Mol. Genet. 6:317-324]. This unusual chromosome rearrangement resulted in WH
      phenotype, clinical manifestations of partial 4p trisomy being mild or absent.
      This observation led us to speculate that the regulatory gene/genes in the
      critical WH region affect the expression of other genes in a dose-dependent
      manner. Haploinsufficiency of this region could be more deleterious than various
      partial trisomies.

PMID- 10069707
TI  - Prenatal diagnosis of the RSH/Smith-Lemli-Opitz syndrome.
AB  - The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is a relatively common, autosomal
      recessive malformation syndrome comprising distinctive facial, limb and genital
      anomalies, and mental retardation. Most patients with a clinical diagnosis of
      RSH/SLOS have a defect of cholesterol biosynthesis at the level of 3beta
      hydroxysteroid-delta7-reductase, resulting in a decreased level of cholesterol
      and an increased level of 7-dehydrocholesterol (7DHC) in body fluids and tissues.
      We report on our experience with the prenatal diagnosis of RSH/SLOS by
      quantitative sterol chromatography in amniotic fluid (AF) and chorionic villus
      (CV). Of 76 AF and nine CV samples analyzed for various indications, 20 were
      diagnostic of RSH/SLOS based on an increased level of 7DHC in the fluid or
      tissue. Of 39 fetuses at a 25% risk for RSH/SLOS, 10(25.6%) were affected. Twenty
      nine pregnancies not known to be at risk for RSH/SLOS were studied because of
      either a fetal abnormality characteristic of RSH/SLOS detected by ultrasound, a
      low maternal serum uE3 level (MSuE3), or both. None of the pregnancies tested,
      because of a low MSuE3 but lacking a sonographic abnormality characteristic of
      RSH/SLOS, was affected. However, three of four pregnancies with a low MSuE3 and
      an RSH/SLOS-type fetal abnormality were positive. RSH/ SLOS was diagnosed in two
      additional pregnancies on which MSuE3 data were not available but in which fetal
      anomalies were identified. Of these five RSH/SLOS fetuses identified in
      pregnancies not otherwise at risk for RSH/SLOS, the presenting sonographic
      anomaly was either polydactyly, ambiguous genitalia, or both. Evaluation of the
      biochemical parameters and clinical severity of RSH/SLOS showed that there was an
      inverse correlation between clinical severity and both the level of AF 7DHC and
      the level of MSuE3. Based on these earlier and more extensive studies, we
      conclude that accurate prenatal diagnosis of RSH/ SLOS is possible by sterol
      analysis of AF and, most likely, CV specimens as well. Furthermore, our findings
      suggest that MSuE3 levels in combination with sonography may provide useful
      diagnostic and prognostic information in the absence of a family history of
      RSH/SLOS.

PMID- 10069708
TI  - Adrenal insufficiency in Smith-Lemli-Opitz syndrome.
AB  - We describe three unrelated patients with adrenal insufficiency and RSH or Smith
      Lemli-Opitz syndrome (SLOS), a disorder due to deficient synthesis of
      cholesterol. These patients presented with hyponatremia, hyperkalemia, and
      decreased aldosterone-to-renin ratio, which is a sensitive measure of the renin
      aldosterone axis. All patients had profound serum total cholesterol deficiency
      (14-31 mg/dl) and marked elevation of 7-dehydrocholesterol (10-45 mg/ dl). Two
      patients were newborn infants with 46, XY karyotypes and complete failure to
      masculinize; one of these patients also had cortisol deficiency. Both patients
      died within 10 days of birth of cardiopulmonary complications while on adrenal
      replacement therapy. The third patient diagnosed with SLOS at birth presented at
      age 7months with fever and diarrhea and was noted to have profound hyponatremia.
      This patient is maintaining normal serum electrolytes on mineralocorticoid
      replacement. We conclude that adrenal insufficiency may be a previously
      undetected and treatable manifestation in SLOS. We hypothesize that deficiency of
      cholesterol, an adrenal hormone precursor, may lead to insufficient synthesis of
      adrenal steroid hormones.

PMID- 10069709
TI  - Clinical spectrum of infantile free sialic acid storage disease.
AB  - Infantile free sialic acid storage disease (ISSD) is a rare autosomal recessive
      metabolic disorder caused by a lysosomal membrane transport defect, resulting in
      accumulation of free sialic acid within lysosomes. Only a few cases have been
      described. We report on three new cases of ISSD with different modes of
      presentation: an infant with nephrotic syndrome, a case of fetal and neonatal
      ascites with heart failure, and a case of fetal ascites with esophageal atresia
      type III. From these patients and a review of the literature (27 cases total) we
      draw the following conclusions. 1) "Coarse facies," fair complexion,
      hepatosplenomegaly, and severe psychomotor retardation are constant findings in
      this disorder. 2) Nephrotic syndrome occurred in most cases (four in seven) in
      which renal evaluation was performed. Therefore, ISSD is an important cause of
      nephrosis in infants with a storage disorder phenotype. 3) Fetal/neonatal ascites
      or hydrops was the mode of presentation in 13 (60%) of 21 cases. Thus, ISSD
      enters in the differential diagnosis of hydrops fetalis with a storage disease
      phenotype. 4) Cardiomegaly was evident in nine cases. 5) Corneae were always
      clear, and albinoid fundi were reported in five cases. 6) Dysostosis multiplex
      was not prominent. 7) Bone marrow aspiration could be negative. 8) Death ensued
      in early infancy with a mean age of 13.1 months. All reported deaths were caused
      by respiratory infections.

PMID- 10069710
TI  - Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian
      population: from LGMD2A to LGMD2G.
AB  - The autosomal recessive limb-girdle muscular dystrophies (AR-LGMDs) are a
      heterogeneous group of disorders of progressive weakness of the pelvic and
      shoulder girdle musculature. The clinical course is characterized by great
      variability, ranging from severe forms with onset in the first decade and rapid
      progression resembling clinically Xp21 Duchenne muscular dystrophy (DMD) to
      milder forms with later onset and slower course. Eight genes are mapped for the
      AR-LGMDs; they are: LGMD2A (CAPN3) at 15q, LGMD2B (dysferlin) at 2p, LGMD2C
      (gamma-SG) at 13q, LGMD2D (alpha-SG) at 17q, LGMD2E (beta-SG) at 4q, LGMD2F (6
      SG) at 5q, LGMD2G at 17q, and more recently LGMD2H at 9q. The LGMD2F (delta-SG)
      and LGMD2G genes were mapped in Brazilian AR-LGMD families. Linkage analysis in
      two unlinked families excluded the eight AR-LGMD genes, indicating that there is
      at least one more gene responsible for AR-LGMD. We have analyzed 140 patients
      (from 40 families) affected with one of seven autosomal recessive LGMD loci, that
      is, from LGMD2A to LGMD2G. The main observations were: 1) all LGMD2E and LGMD2F
      patients had a severe condition, but considerable inter- and intra-familial
      clinical variability was observed among patients from all other groups; 2) serum
      CK activities showed the highest values in LGMD2D (alpha-SG) patients among
      sarcoglycanopathies and LGMD2B (dysferlin) patients among nonsarcoglycanopathies;
      3) comparison between LGMD2A (CAPN3) and LGMD2B (dysferlin) showed that the first
      have on average a more severe course and have calf hypertrophy more frequently
      (86% versus 13%); and 4) inability to walk on toes was observed in approximately
      70% of LGMD2B patients.

PMID- 10069711
TI  - Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic
      variability of 1367Cys/Arg, and its stability in a population of Finnish
      centenarians.
AB  - The Werner syndrome gene (WRN) encodes a novel helicase of 1,432 amino acids.
      Homozygous mutations, all of which result in the truncation of the protein, lead
      to Werner syndrome. However, little is known about the role of WRN in "normal"
      aging. We have identified four missense polymorphisms and four conservative
      polymorphsims in WRN gene. A single study showed that a polymorphism at amino
      acid 1367 Cys(TTG)/ Arg(CTG) is associated with a variation in risk of myocardial
      infarction among a Japanese population. The 1367 Cys/Arg polymorphism was
      examined during aging in three different populations: Finnish, Mexican, and North
      American. The frequencies of 1367 Cys were higher than those of 1367 Arg in all
      the populations examined, though the frequencies varied among populations. The
      frequency of the 1367 Arg allele, thought to be protective against myocardial
      infarction in a Japanese population, was approximately three times higher in the
      North American and Finnish adult populations. When newborns and centenarians were
      compared within the Finnish population, no differences were observed in the
      proportions of 1367 Cys/Arg across age groups. Within the Finnish population, we
      confirmed a significant decrease of the APOE epsilon2 allele and an increase in
      the epsilon4 allele in newborn infants compared with centenarians. Thus, unlike
      the APOE polymorphism, there is no evidence of an association of this WRN
      polymorphism with longevity.

PMID- 10069712
TI  - Congenital stapes ankylosis, broad thumbs, and hyperopia: report of a family and
      refinement of a syndrome.
AB  - We report on a family with conductive hearing loss due to congenital stapes
      ankylosis, and with hyperopia, broad thumbs, and broad first toes. Neither of the
      studied relatives had symphalangism, possibly distinguishing this syndrome as an
      entity separate from the facio-audio-symphalangism and proximal symphalangism
      syndromes. An alternative possibility is that this family falls within the
      spectrum of the facioaudio-symphalangism and proximal symphalangism syndromes.
      Visualization of the ossicular chain, and ophthalmologic and radiologic studies
      are important in the evaluation of families with congenital conductive hearing
      loss. A characteristic physiognomy in our patients is present; this autosomal
      dominant syndrome was first described by Teunissen and Cremers [1990:
      Laryngoscope 100:380-384].

PMID- 10069713
TI  - Melorheostosis in a family with autosomal dominant osteopoikilosis.
AB  - We describe a 19-year-old woman with melorheostosis and osteopoikilosis (mixed
      sclerosing bone dysplasia). Her sister and mother had osteopoikilosis, but no
      evidence of melorheostosis. Isolated melorheostosis and melorheostosis with
      osteopoikilosis are sporadic disorders. Osteopoikilosis is an autosomal dominant
      trait. Mixed sclerosing bone dysplasia in a family with autosomal dominant
      osteopoikilosis raises the possibility that the two bone disorders may be
      related. This family and that of Butkus et al. [1997: Am J Med Genet 72:43-46]
      suggest that the melorheostosis could be due to a second mutation at the same
      locus as that which causes autosomal dominant osteopoikilosis.

PMID- 10069714
TI  - Tracheal agenesis revisited: analysis of associated anomalies.
AB  - We describe five new cases of tracheal agenesis and report on epidemiological and
      numerical analyses of nearly 100 such cases with multiple congenital anomalies.
      Malformations seen with tracheal agenesis form patterns which overlap with, but
      are distinct from, VACTERL association. They have a high frequency of other lower
      respiratory tract anomalies; e.g., laryngeal atresia and lung lobation defects,
      and complex heart anomalies, but fewer anal and vertebral malformations. Cluster
      analysis of the malformations in 86 patients identified four consistent groups.
      Anomalies in the first group were primarily restricted to the trachea, larynx,
      and cardiovascular system. In the second group, the patients had more severe
      cardiac defects, and lung lobation anomalies, while in the third they had a
      caudal component in addition to thoracic abnormalities, with anal and renal
      anomalies being common. Each of these groups showed a male excess and may
      represent increasingly severe perturbations in development fields encompassing
      the developing respiratory tract. Although the nature of the causative insult is
      unknown and probably heterogenous, one underlying pathogenetic mechanism may be
      abnormal epithelial-mesenchymal interactions. Patients in the fourth group also
      had multisystem involvement with a high incidence of aberrant vessels, complex
      cardiac malformations, lung lobation defects, and anomalies of other foregut
      derivatives. The sex ratio in this group was normal and such cases could
      represent a disturbance in the primary development field during blastogenesis
      with secondary vascular disruptions. Complete tracheal agenesis is a lethal
      anomaly. However, segmental forms may be correctable and, in this group of
      infants, the nature of associated anomalies may well determine long-term
      prognosis.

PMID- 10069715
TI  - Consanguinity and recurrence risk of birth defects: a population-based study.
AB  - Recurrence risks give insight into the causes of birth defects and are useful in
      genetic counseling. There are few population-based studies of recurrence of birth
      defects for subsequent sibs with consanguineous parents. The aim of this study
      was to estimate and compare the recurrence risk of birth defects for offspring of
      first cousins and nonconsanguineous parents. The study population consisted of
      all single births with a previous sib born in Norway between 1967 and 1995.
      Altogether 660,398 children had nonconsanguineous parents, and 3,583 had parents
      who were first cousins. For nonconsanguineous parents the risk of a birth defect
      for the subsequent sib was 15 per 1,000 births (95% confidence interval: 14.5
      15.1) if the previous child did not have a birth defect and 33 (95% confidence
      interval: 30-37) if the previous child had a birth defect. For parents who were
      first cousins the risk of a birth defect for the subsequent sib was 36 per 1,000
      (95% confidence interval: 30-42) if the previous child did not have a birth
      defect and 68 (95% confidence interval: 33-122) if the previous child had a birth
      defect. The risk of recurrence of birth defects is higher for subsequent sibs
      with first-cousin parents than for those with nonconsanguineous parents. This
      difference indicates the degree to which the increased homozygosity among
      offspring of consanguineous parents influences the risk of recurrence of birth
      defects.

PMID- 10069716
TI  - Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome:
      three new cases and review of nine patients.
AB  - Oculo-facio-cardio-dental syndrome is a very rare condition. So far, only nine
      cases have been documented. We report on three additional female patients
      representing the same entity. The clinical findings were: congenital cataract,
      microphthalmia/microcornea, secondary glaucoma, vision impairment, ptosis, long
      narrow face, high nasal bridge, broad nasal tip with separated cartilages, long
      philtrum, cleft palate, atrial septal defect, ventricular septal defect, and
      skeletal anomalies. The following dental abnormalities were found:
      radiculomegaly, delayed dentition, oligodontia, root dilacerations (extension),
      and malocclusion. For the first time, fusion of teeth and hyperdontia of
      permanent upper teeth were seen. In addition, structural and morphological dental
      changes were noted. These findings expand the clinical spectrum of the syndrome.

PMID- 10069717
TI  - Different phenotypic expression in relatives with fabry disease caused by a W226X
      mutation.
AB  - Two male relatives with Fabry disease presented striking differences in clinical
      symptoms and age of onset. The propositus had retarded statural growth and
      skeletal dysplasia while his nephew suffered mainly from aggravating
      acroparesthesia and celiac disease. Fabry disease is an X-linked inborn error of
      glycosphingolipid metabolism resulting from deficient activity of the lysosomal
      hydrolase alpha-galactosidase A (alpha-Gal A) enzyme. The alpha-Gal A gene is
      located at Xq22.1. Efforts to establish genotype-phenotype correlations have been
      limited because most patients have private mutations. In previous clinical
      studies performed in families with Fabry disease, marked differences in phenotype
      are described between affected relatives. This family also demonstrates the
      difficulty in predicting the clinical phenotype in patients and relatives with
      the same alpha-Gal A mutation. Furthermore, in the absence of a family history,
      the diagnosis may be easily missed.

PMID- 10069718
TI  - Branchio-otic syndromes imbroglio.

PMID- 10069719
TI  - Clinical differences between North African and Iraqi Jews with familial
      Mediterranean fever.

PMID- 10069720
TI  - Is there an association of Down Syndrome and omphalocele?

PMID- 10069721
TI  - Simultaneous assessment of right ventricular function and hypertrophy by Tc-99m
      MIBI.
AB  - PURPOSE: Tc-99m MIBI allows the simultaneous performance of cardiac blood pool
      scintigraphy and myocardial SPECT. The authors performed studies to determine
      whether right ventricular function and hypertrophy can be evaluated
      simultaneously using Tc-99m MIBI in patients with right heart disease. METHODS:
      Using right heart catheterization, several parameters of pulmonary circulation
      were measured, including right ventricular ejection fraction, in 23 patients with
      chronic pulmonary disease and pulmonary vascular disease. Within 1 week, right
      heart blood pool scintigraphy was performed using the first-pass method using Tc
      99m MIBI. The right ventricular ejection fraction calculated from right heart
      blood pool scintigraphy was compared with that measured using right heart
      catheterization. Myocardial SPECT was performed 1 hour after right heart blood
      pool scintigraphy. On the short axis images, which allowed optimal visualization
      of the right ventricle, the right and left ventricular free walls were
      established as regions of interest. Myocardial wall counts were determined. The
      right ventricular uptake: left ventricular uptake ratio was calculated to study
      the relation of that ratio to mean pulmonary artery pressure and total pulmonary
      resistance. RESULTS: A significant correlation was observed between the right
      ventricular ejection fraction calculated on right heart catheterization and that
      calculated on right heart blood pool scintigraphy. The right ventricular
      uptake:left ventricular uptake ratio correlated positively with pulmonary artery
      pressure and total pulmonary resistance. CONCLUSION: These results suggest that
      Tc-99m MIBI allows simultaneous noninvasive evaluation of cardiac function and
      structure, which previously was considered impossible in patients with right
      heart disease.

PMID- 10069722
TI  - Tc-99m HDP uptake in cardiac amyloidosis.
AB  - Amyloidosis is characterized by the soft-tissue deposition of amyloid protein. It
      may occur as a primary disorder but more often is seen as a manifestation of
      chronic illness. Scattered reports of the affinity of amyloid for bone scanning
      agents have appeared over many years. Isolated cardiac uptake of Tc-99m HDP is
      described in a patient with biopsy-proved cardiac amyloidosis on a background of
      tuberculosis, prostate cancer, and coronary artery disease.

PMID- 10069723
TI  - Detection of cardiac myxoma by F-18 FDG PET.
AB  - Intracardiac tumors occur infrequently and are difficult to diagnose with CT and
      MRI. The authors describe the successful imaging of a right atrial myxoma with F
      18 FDG PET.

PMID- 10069724
TI  - Scintigraphic diagnosis of polysplenia in the adult.
AB  - PURPOSE: The authors describe an adult patient with low index of suspicion for
      polysplenia. The diagnostic contribution of various investigative modalities is
      considered, and the key role of scintigraphy is specifically highlighted.
      RESULTS: CT scan findings revealed multiple abdominal and retroperitoneal masses.
      Needle biopsy of a flank mass was nonspecific. Tc-99m sulfur colloid liver spleen
      scintigraphy and Tc-99m heat-denatured RBC scans showed the presence of
      polysplenia. CONCLUSIONS: Multiple spleens can be mistaken for abdominal
      neoplasms on CT. Biopsy results may not always be helpful. In patients in whom
      there is such a diagnostic dilemma, Tc-99m heat-denatured RBC scans can
      successfully establish the definitive diagnosis of polysplenia.

PMID- 10069725
TI  - Hepatopulmonary syndrome in Gaucher disease with right-to-left shunt: evaluation
      and measurement using Tc-99m MAA.
AB  - Hepatomegaly is a common manifestation in Gaucher disease. In some patients with
      the disease, hepatic fibrosis and portal hypertension are observed. A patient
      with Gaucher disease with the hepatopulmonary syndrome associated with severe
      cyanosis and hypoxemia was examined for intrapulmonary right-to-left shunt using
      Tc-99m MAA. Quantitative evaluation revealed an approximately 50% right to left
      shunt as indicated by Tc-99m MAA activity in the lungs and systemic organs.

PMID- 10069726
TI  - Diagnostic accuracy of salivary scintigraphic indices in xerostomic populations.
AB  - PURPOSE: Three decades of work to enhance the diagnostic accuracy of salivary
      scintigraphy have generated various plausible decision criteria. This study
      evaluates four commonly cited numeric indices in studies of xerostomic
      populations and how accurately they identify Sjogren's syndrome, chronic
      sialadenitis, radiation sialadenitis, and drug effects and distinguish each from
      the other. METHODS: Stimulated dynamic salivary scintigraphy was performed on 295
      xerostomic patients and on 31 controls. The nonparametric area under the receiver
      operating characteristic curves expressed the diagnostic accuracy of the
      following scintigraphic indices: the parotid:submandibular ratio of unstimulated
      glandular activity, the peak:baseline uptake ratio, its time of occurrence, and
      the stimulated excretion fraction. RESULTS: The stimulated excretion fraction
      distinguished Sjogren's syndrome and radiation sialadenitis from healthy states
      with respective accuracies of 0.78 and 0.90. The maximum diagnostic payoff in
      Sjogren's syndrome occurred at a cutoff of 73%, yielding a 73% rate of test
      sensitivity and a 73% rate of specificity. The other three indices were not
      useful. Even the stimulated excretion fraction performed indifferently or poorly
      in most other diagnostic tasks. CONCLUSIONS: In the scintigraphic examination of
      xerostomic and healthy populations, an acceptable diagnostic utility of the
      stimulated excretion fraction was evident only in Sjogren's syndrome and
      radiation sialadenitis. When presented with differential diagnostic alternatives
      not involving radiation sialadenitis, none of the four numeric indices performed
      acceptably.

PMID- 10069727
TI  - Gallium accumulation in marrow lymphocytes.
AB  - A case of Ga-67 and Tc-99m WBC imaging in a patient is shown in which the
      discrepancy in the accumulation of the two imaging agents in radiated bone
      indicates that gallium accumulated predominantly in marrow lymphocytes in the
      skeleton of this patient.

PMID- 10069728
TI  - Intra- and interoperator variations in region-of-interest drawing and their
      effect on the measurement of glomerular filtration rates.
AB  - PURPOSE: Quantitative results are often obtained from images after drawing
      regions of interest (ROIs) about the organ or area being evaluated. The accuracy
      and reproducibility of ROIs is an important aspect of quality-control protocols.
      Attempts to increase ROI accuracy and precision by generating them automatically
      must be compared with manually processed images to evaluate the success of the
      automatic methods. Operators' abilities to reproduce ROIs and the effect this has
      on the reproducibility of estimating glomerular filtration rate from renograms
      were assessed. METHODS: Estimation of the glomerular filtration rate using
      Sampson's method requires a) exclusion ROIs around both kidneys for background
      subtraction, b) whole-kidney ROIs, and c) exclusion ROIs for the collecting
      system. Two nuclear medicine professionals were asked to produce glomerular
      filtration rate estimates for 20 patients with diverse renal function. This was
      repeated 1 month later. The intra- and interoperator variations were calculated
      for the glomerular filtration rate results and on a pixel basis for the ROIs.
      RESULTS: THE percentage of common pixels, on average, for a) intraoperator
      repeats and b) interoperator comparisons were a) 95%, 94%, 85%, and b) 94%, 93%,
      and 81% for region types 1, 2, and, 3, respectively. Analysis of variance for the
      glomerular filtration rate estimates showed significant variations in estimates
      for left kidneys (P < 0.025) but none (P > 0.1) for right kidneys. CONCLUSION:
      Spatial reproducibility in ROI drawing does not necessarily relate directly to
      the associated quantitative reproducibility.

PMID- 10069729
TI  - False-positive result of a total-body scan caused by benign thyroidal tissue
      after I-131 ablation.
AB  - This case report illustrates a false-positive result of an I-131 total-body scan
      caused by abnormal, noncancerous thyroid tissue. A 39-year-old woman underwent an
      open biopsy and thyroidectomy for a papillary thyroid carcinoma. She was treated
      by ablation with 150.8 mCi I-131. A follow-up total-body scan revealed a solitary
      focus of increased activity near the midline at the upper border of the larynx
      that was subsequently excised. Histologic analysis indicated a fragment of
      thyroid tissue with chronic inflammation, fibrosis, and squamous metaplasia. No
      evidence of thyroid carcinoma was present. Hypofunctioning or nonfunctioning
      residual tissue within the thyroglossal duct may have been suppressed under
      euthyroid conditions, protecting it from ablation. This tissue may have become
      stimulated by the high thyroid-stimulating hormone levels, accumulating I-131 and
      producing a false-positive result of the scan.

PMID- 10069730
TI  - Photopenic area visualized on bone scintigraphy in a patient with eosinophilic
      granuloma.

PMID- 10069731
TI  - TI-201 SPECT in pseudotumoral multiple sclerosis.

PMID- 10069732
TI  - Scintigraphy of a double renal transplant from an infant donor.

PMID- 10069733
TI  - Double-phase Tc-99m sestamibi scintigraphy in a patient with uremia and secondary
      hyperparathyroidism: an aid for subtotal parathyroidectomy.

PMID- 10069734
TI  - "Light bulb" bladder due to massive lymphadenopathy in prostate cancer.

PMID- 10069735
TI  - Iodine-131 MIBG uptake in hydronephrosis due to compression by a large adrenal
      mass.

PMID- 10069736
TI  - The role of Ga-67 whole-body and Tc-99m DMSA renal scan in primary bilateral B
      cell renal non-Hodgkin's lymphoma.

PMID- 10069737
TI  - Radionuclide accumulation in the proximal esophagus during esophageal
      scintigraphy.

PMID- 10069738
TI  - F-18 FDG PET scan of a metastatic pineoblastoma.

PMID- 10069739
TI  - Tc-99m DTPA uptake in malignant fibrous histiocytoma masquerading as a phantom
      kidney.

PMID- 10069740
TI  - Tc-99m DMSA renal scan in polyarteritis nodosa with bilateral intraparenchymal
      renal artery aneurysms.

PMID- 10069741
TI  - Internal mammary nodal metastases from breast cancer detected by
      scintimammography.

PMID- 10069742
TI  - Stromal tumor causing small intestinal bleeding: scintigraphic localization.

PMID- 10069743
TI  - Painful Schmorl's node: another cause of vertebral photopenia on Indium-111
      labeled leukocyte scintigraphy.

PMID- 10069744
TI  - Imaging of septate gallbladder.

PMID- 10069747
TI  - Current readings in nuclear medicine.

PMID- 10069745
TI  - Location of regional intestinal lymphangiectasia using Tc-99m dextran
      lymphoscintigraphy.

PMID- 10069748
TI  - Drug use in greater Accra, Ghana: pilot study.
AB  - The goal of this exploratory study of drug use in greater Accra, Ghana, is to
      expand our understanding of the rapidly changing drug problem in Africa. Until
      the last decade, Ghana, with its excellent transportation links, was only a
      transit point in the narcoscape. Drug use was confined to Indian hemp or
      marijuana use. This exploratory study, conducted in the summer of 1996, confirms
      that such drugs as heroin and cocaine, as well as psychotropic substances, are
      now diverted for local consumption. This conclusion is based on a survey of 1 17
      former and current drug users in the greater Accra area. The portrait of the
      typical drug user that emerges from this pilot study is a 30-year old, working
      class or underclass male who uses cocaine or heroin. In addition, many drug users
      resort to petty theft to support their habit because they are usually unemployed.

PMID- 10069749
TI  - The development of advanced drinking habits in adolescence--a longitudinal study.
AB  - This paper aims at exploring the relations between early risk factors and the
      development of advanced drinking habits in adolescence. Data were derived from
      the longitudinal research program Individual Development and Adjustment. Results
      confirm earlier findings from longitudinal studies in this field. Three important
      factors have been identified: significant others, general sociability, and
      personality/conduct. More important, though, is that results indicate that
      knowledge about one or two background characteristics is not enough to make
      predictions of adolescent drinking habits. Rather, it is the ensemble of
      circumstances that together lead to an increased risk for advanced drinking
      habits in adolescence.

PMID- 10069750
TI  - Polydrug misuse patterns in Sweden. Gender differences.
AB  - The main purpose of this study was to draw up literature about polydrug misuse
      and to study the patterns and gender differences of polydrug misuse in a sample
      (N = 1,268) of narcotics users in Sweden. They were interviewed personally when
      entering treatment about their drug misuse from debut to established misuse. A
      nationwide case-finding study was used to verify the results. First, results
      indicate that those studied were primarily polydrug misusers and that alcohol
      consumption was very high. Second, gender differences were found. Third, a basic
      characteristic of multiple substance use was formulated. The findings are
      discussed in relation to new knowledge of consumption patterns.

PMID- 10069751
TI  - Naturalistic observation of athletic drug-use patterns and behavior in
      professional-caliber bodybuilders.
AB  - Athletic performance-enhancing drug use is widespread. Awareness in the medical
      community lags because various athletic subcultures have not been penetrated by
      conventional medical literature. This report presents a current and comprehensive
      assessment of drugs used by professional-caliber bodybuilders to enhance athletic
      performance. The scale of drug use documented significantly exceeds all previous
      reports from athletic populations and indicates that this group is at significant
      risk for use. Drug-use patterns and behavior encompass multiple domestic,
      foreign, and veterinary agents to create "successful" training programs. The
      presence of interathlete and intersport communication at amateur and professional
      levels creates a wide application for this information in athletic settings.
      Since use may not be limited to the competitive athlete, a heightened awareness
      will aid practitioners in correlating clinical observations with accurate
      athletic drug-use information.

PMID- 10069752
TI  - A pilot study of the social construction of the meanings attached to alcohol use:
      perceptions from India.
AB  - The literature on alcoholism is replete with various cultural interpretations of
      alcohol use and alcoholism. However, many of those interpretations have not
      considered the meanings associated with drinking alcohol, a perspective that goes
      beyond simply examining the causes of alcoholism. The present study focused on
      the social construction of the meanings associated with use of alcohol and
      alcoholism from an Indian perspective. Using qualitative methods, the researcher
      collected ideas on the meanings of alcohol use from eight alcohol-dependent
      clients of a South India alcoholism treatment center who participated in focus
      groups and in-depth interviews. An important aspect of this research was that the
      researcher considered the alcohol-dependent participants as the "experts" who
      validated their point of view. Several themes emerged: Alcohol use is a symbol of
      economic status, caste, a person's karma, a period of turmoil, and gender
      privilege. It is important that social workers and other intervention agents
      understand the meanings of alcohol use for each alcohol-dependent client so that
      they may plan creative and individualized interventions.

PMID- 10069753
TI  - Characteristics of inconsistent respondents who have "ever used" drugs in a
      school-based sample.
AB  - This study examines the predictors of inconsistent responses from adolescents to
      questions about whether they ever used alcohol, cigarettes, and marijuana. Male
      adolescents had significantly higher rates of inconsistent responses than female
      adolescents. Black and Hispanic adolescents had significantly higher rates of
      inconsistent responses regarding ever using alcohol and cigarettes (only for
      Black) than White adolescents. The subjects' living status and academic
      achievements were significant predictors of inconsistent responses regarding ever
      using marijuana. Thus, these results are consistent with the notion that
      inconsistent responses may bias the estimation of the prevalence of ever using
      drugs in multivariate analyses.

PMID- 10069754
TI  - Generalizing ethnicity in youth drug misuse research.
AB  - Policies for providing prevention programs in multicultural communities are
      recommended. These policies are suggested after an assessment of the current
      literature on Mexican-origin youth and drug use. Additionally, a multicultural
      value system for communication is identified and suggested for considering drug
      prevention in practice, policy, and research.

PMID- 10069755
TI  - Opiate withdrawal outcome: the predictive ability of admission measures from the
      family assessment device (F.A.D.)
AB  - The Family Assessment Device (F.A.D.) was administered to a sample of 57 opiate
      misusers at admission for inpatient detoxification. Logistic regression analyses
      showed that the odds of a premature discharge against medical advice from the
      Unit were increased by progressively poorer ratings of family functioning in the
      areas of problem solving and roles, while progressively poorer ratings of
      functioning in the areas of communication and behavioral control were associated
      with decreasing odds of a premature discharge. It was concluded that further
      research was required to better understand and utilize the potentially supportive
      role of families in this phase of treatment.

PMID- 10069756
TI  - Long-term consequences of deep vein thrombosis.
AB  - Following an overt episode of deep vein thrombosis (DVT), the long-term prognosis
      of the patient is predominantly obscured by three natural complications:
      recurrence of venous thromboembolism (VTE), post-thrombotic syndrome and death.
      Antithrombotic treatments have been proven effective in preventing recurrence of
      VTE but carry the risk of major bleeding. A high mortality rate persists during
      the first year following an acute VTE, with a small but continuing risk beyond
      the first year. Recurrences of VTE account for the minority of causes of deaths.
      With effective initial anticoagulant treatment, the early (within approximately 3
      months) risk of recurrence is 3-6%. Long-term follow-up studies have shown that
      although the risk of recurrence of VTE beyond the first 6 months is lower, the
      risk persists over several years. Approximately 25% of DVT patients remain
      asymptomatic in the long term but severe signs of post-thrombotic syndrome
      (ulceration) are observed in 2-10% of patients 10 years after DVT. Major advances
      have been made in the management of acute VTE but the excess risks of death,
      recurrence of VTE and post-thrombotic syndrome persist for several years
      following the initial event. Appropriate therapeutic strategies for these events
      are still being developed and future study should be directed towards finding the
      optimal regimen for patients who require prolonged treatment.

PMID- 10069757
TI  - The economic impact of treating deep vein thrombosis with low-molecular-weight
      heparin: outcome of therapy and health economy aspects.
AB  - Subcutaneous low-molecular-weight heparin (LMWH) is at least as safe and
      effective as classical intravenous heparin therapy for the treatment of proximal
      vein thrombosis. Anticoagulant monitoring and intravenous administration are not
      required with LMWH treatment, therefore this therapy may offer economic
      advantages. An economic evaluation of these therapeutic approaches was performed
      comparing the costs and effectiveness. The evaluation was aimed at helping
      decision-makers to maximize the health of the population served, subject to
      available resources. The American-Canadian Thrombosis Study was a multicentre,
      randomized, double-blind clinical trial that compared treatment by initial
      continuous intravenous infusion of heparin (followed by 3 months of warfarin
      therapy) with a once-daily dose of subcutaneous LMWH, tinzaparin sodium (followed
      by 3 months of warfarin treatment) in patients with acute proximal deep vein
      thrombosis. In the LMWH-treated group, the cost incurred for 100 patients was
      $399,403 (Canadian) or $335,687 (US) with a frequency of objectively documented
      recurrent venous thromboembolism of 2.8%. In the intravenous heparin-treated
      group, the cost incurred for 100 patients was $ 414,655 (Canadian) or $ 375,836
      (US), with a frequency of objectively documented recurrent venous thromboembolism
      of 6.9%. These results show a cost saving of $ 15,252 (Canadian) or $ 40,149 (US)
      with the use of LMWH. Multiple sensitivity analyses did not alter the findings of
      the study which indicated that LMWH therapy is at least as safe and effective but
      less costly than intravenous heparin treatment. The potential for outpatient
      therapy in up to 37% of patients who are receiving LMWH would substantially
      augment the cost-saving. The cost-effectiveness findings presented in this paper
      are based on the assumption that all costs are covered by a single payer.
      Outpatient management in many countries will shift the healthcare costs from the
      healthcare payer to the patient, increasing the economic burden to the patient.

PMID- 10069758
TI  - Long-term prophylaxis in venous thromboembolism: LMWH or oral anticoagulation?
AB  - Warfarin remains the standard drug for secondary prophylaxis following venous
      thromboembolism, however this treatment is not ideal. In patients for whom
      monitoring is problematic or who have a high risk of bleeding complications,
      other possible solutions have been explored. Unfractionated heparin has been used
      to a limited extent in these situations and requires dose adjustment in order to
      achieve an acceptable efficacy. Low-molecular-weight heparin (LMWH) is a valuable
      alternative to warfarin for these patients and for thromboprophylaxis during
      pregnancy. In several subgroups of patients with venous thromboembolism the use
      of a LMWH instead of warfarin could offer specific advantages. The combination of
      warfarin and LMWH is warranted in patients for whom it is predicted that warfarin
      treatment alone may fail. The optimal dose of LMWH in long-term prophylaxis has
      not been evaluated in a properly designed study and the optimal duration of
      prophylaxis with LMWH is thought to be similar to that for warfarin.

PMID- 10069759
TI  - The special case of venous thromboembolism in pregnancy.
AB  - Pulmonary thromboembolism remains a major cause of maternal death in the Western
      world. The frequency of antepartum deaths, including deaths in the first and
      second trimester, which can be associated with early pregnancy problems such as
      hyperemesis, is similar in number to the deaths occurring following delivery.
      Risk factors for deep vein thrombosis have been identified and include age > 35
      years, operative delivery (particularly emergency Caesarean section), obesity and
      a personal or family history of thrombosis or thrombophilia. These risk factors
      should be used to guide administration of thromboprophylaxis during both
      pregnancy and the post-partum period, particularly after Caesarean section.
      Specific consideration towards thromboprophylactic agents is required. Warfarin
      crosses the placenta, is a known teratogen when used in early pregnancy and can
      also be associated with bleeding problems in the foetus, particularly at the time
      of delivery. Thus, warfarin has a limited use in the antenatal period and is
      usually only employed in patients such as those with artificial heart valves who
      require long-term anticoagulation. However, as warfarin does not cross the breast
      in any significant amount, it is suitable during breast feeding. In contrast,
      heparin does not cross the placenta or the breast therefore foetal problems are
      not associated with this treatment. However, heparin can be associated with
      problems such as heparin-induced osteoporosis, allergy and heparin-induced
      thrombocytopenia. The risk of some of these complications can be reduced by the
      use of low-molecular-weight heparins. When venous thromboembolism is suspected in
      pregnancy, it is critically important to obtain an objective diagnosis. This will
      include real-time or duplex ultrasound scan of the legs to elaborate the venous
      system, ventilation perfusion lung scan and, occasionally, venography. Treatment
      of established venous thromboembolism is similar to that in the non-pregnant
      patient and it is likely that low-molecular-weight heparins will play a major
      role in thromboprophylaxis in the future.

PMID- 10069760
TI  - Antithrombotic therapy in coronary ischaemia: the expanding role of low-molecular
      weight heparin.
AB  - Low-molecular-weight heparins (LMWHs) have been rigorously evaluated in the
      management of acute coronary ischaemia. The results of clinical trials suggest
      that LMWHs are effective in reducing major ischaemic outcomes in patients with
      unstable angina and non-Q-wave myocardial infarction. In one study, LMWH was
      shown to be more effective than heparin. The clinical utility of LMWHs given
      subcutaneously in a fixed-dose without the need for monitoring results in major
      cost savings. The accumulating evidence suggests that LMWHs are safe, effective
      alternatives to standard heparin in unstable coronary disease and offer practical
      and therapeutic advantages, representing an important advance in the management
      of acute coronary ischaemia.

PMID- 10069761
TI  - Venous thromboembolism in malignancy and malignancy in venous thromboembolism.
AB  - The activation of coagulation in patients with cancer contributes significantly
      to morbidity and mortality rates and may play a fundamental role in the host
      response to growing tumours. Patients with cancer are clearly at high risk for
      the development of venous thromboembolism (VTE), particularly during chemotherapy
      and surgery. This situation is aggravated by the use of venous access catheters
      and possibly growth factors. Data derived from large, randomized, controlled
      trials have been used to determine the true incidence of this complication of
      cancer and its treatment. The incidence based on the analyses of these randomized
      controlled trials varies from 1% for limited stage patients with breast cancer
      treated with tamoxifen to 60% for patients with any type of cancer who are
      subjected to orthopaedic surgery and do not receive prophylactic therapy. In view
      of the morbidity and mortality attributable to VTE in cancer, widespread
      utilization of prophylactic anticoagulation therapy, which has proven safe and
      effective in a variety of situations, should be considered. While migratory
      thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of
      cancer in patients with the more typical form of VTE has been the subject of
      intense debate over recent years. Some investigators have suggested that the
      relative risk of being diagnosed with an occult cancer within 6 months of an
      episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the
      cost-effectiveness of aggressive screening for cancer in patients with VTE has
      not yet been defined adequately.

PMID- 10069762
TI  - Mechanisms of hypercoagulation in malignancy and during chemotherapy.
AB  - Patients with cancer are at increased risk for thromboembolic disease. Commonly
      they present with abnormalities of one or more circulating markers of haemostatic
      system activation, underlying a 'hypercoagulable state'. Despite numerous
      investigations which have identified alterations in all of the haemostatic
      components (i.e. coagulation, fibrinolysis, endothelium, platelets and
      monocytes), no firm conclusions have been reached regarding the clinical utility
      of any of these coagulation markers for predicting thrombosis in cancer patients.
      The predictive value of one or more of these tests could help to identify safe
      and effective methods for prophylaxis against thrombotic complications in these
      patients. Plasma clotting abnormalities are usually exacerbated by chemotherapy.
      The mechanisms by which the haemostatic system is activated in malignancy (and
      chemotherapy) are reviewed.

PMID- 10069763
TI  - Thromboprophylaxis in the cancer patient.
AB  - Thrombosis is a common complication in patients with malignant disease resulting
      from tumour elaboration of procoagulants and subsequent activation of
      intravascular coagulation. Cancer therapies (operation, chemotherapy and the use
      of central venous lines) further heighten the risk of thrombosis. The risk of
      thrombosis in cancer operations is of sufficient magnitude to necessitate routine
      thromboprophylaxis, for which low-dose unfractionated heparin or the low
      molecular-weight heparins (LMWHs) have been proven effective and safe. Thrombotic
      complications with chemotherapy have been extensively described in women
      receiving either adjuvant or palliative cytotoxic or hormonal therapy for breast
      carcinoma. The problems are common, but of all the suitable prophylactic
      modalities available, only oral anticoagulants have been evaluated for this
      indication. Thrombosis complicates the use of central venous catheters in the
      cancer patient and both low-dose warfarin and LMWHs are effective in protecting
      against line-associated thrombi. Recent evidence from the retrospective analyses
      of randomized studies comparing unfractionated heparin and LMWH in the treatment
      of deep vein thrombosis have shown a striking mortality reduction among cancer
      patients who received LMWH. The use of LMWHs to prolong survival in patients with
      advanced malignant disease is currently the subject of a prospective, randomized,
      placebo-controlled study.

PMID- 10069764
TI  - Treatment of venous thromboembolism in cancer patients.
AB  - The occurrence of venous thromboembolism complicates the management of the
      patient with malignant disease because of the need for anticoagulant therapy.
      Cancer patients have an ongoing thrombotic stimulus due to the underlying cancer
      and its associated treatments, but are also considered to be at increased risk
      for anticoagulant-related bleeding. In recent years, the results of clinical
      trials have demonstrated the safety and efficacy of bodyweight-adjusted
      subcutaneous low-molecular-weight heparin administered at home for patients with
      acute deep vein thrombosis. This approach is particularly attractive in patients
      with cancer, in whom quality of life is an important consideration. There are no
      trials to date which specifically address the question of the duration of oral
      anticoagulant therapy in cancer patients. However, data can be extrapolated from
      trials evaluating the duration of oral anticoagulant therapy in other high-risk
      patients. Hence, cancer patients should continue oral anticoagulant therapy for
      as long the cancer remains active (usually at least 6 months). There remain a
      number of unanswered questions regarding the clinical management of
      thromboembolism in the cancer patient.

PMID- 10069765
TI  - Thromboprophylaxis in non-surgical patients: who, when and how?
AB  - Because of the serious lack of useable, relevant information, most
      recommendations for prevention of thrombosis in non-surgical patients are
      extrapolations from much larger clinical trials experienced in surgery. Directly
      relevant evidence comes predominantly from very small randomized trials, many of
      them open label and carried out more than 20 years before the introduction of
      more recent and important changes in clinical care that may have substantially
      reduced the baseline thrombosis risk. In these early studies, low-dose heparin
      and low-molecular-weight heparins prevented subclinical deep vein thrombosis in
      ischaemic stroke, myocardial infarction and among elderly medical inpatients.
      Although it is likely that these drugs also prevent subclinical deep vein
      thrombosis after spinal cord injury or other major trauma, and when patients
      require intensive medical care, the supporting evidence in these circumstances
      comes mainly from cohort studies and poorly controlled comparisons. In contrast,
      the heparins have not reduced mortality or demonstrably prevented pulmonary
      embolism after ischaemic stroke or among elderly medical inpatients in large and
      well-conducted clinical endpoint trials, from which no clinically important
      benefit could be demonstrated. From analyses it is suggested that such benefit is
      probably more difficult to demonstrate for medical than for surgical patients. In
      the absence of sufficient information that is specific to medical patients,
      various forms of prophylaxis known to be effective in surgery will continue to be
      applied in high-risk individuals. After venous thromboembolism, it now appears
      that the best duration of oral anticoagulant therapy to prevent a recurrence is
      determined to a greater extent by whether the thrombotic episode was idiopathic
      or triggered by a clinically recognizable cause, whether it was transient or
      continuing, and whether the deep vein thrombosis was extensive, limited to the
      calf veins or was a first or recurrent event.

PMID- 10069766
TI  - Unfractionated heparin and low-molecular-weight heparin for the initial treatment
      of acute venous thromboembolism.
AB  - Anticoagulant drugs represent the therapy of choice for the initial treatment of
      venous thromboembolism. Unfractionated heparin (UFH) in adjusted doses and low
      molecular-weight heparin (LMWH) in fixed doses are equally as effective and safe.
      Proper use of UFH requires considerable expertise, can cause inconvenience and
      has limitations. The use of LMWHs has multiple advantages over UFH including a
      more predictable dose-response and fixed administration dose. These properties
      make the treatment of suitable patients feasible in an outpatient setting. In two
      major clinical trials addressing the treatment of deep vein thrombosis,
      outpatient management with LMWH was associated with a substantial cost reduction
      compared with inpatient treatment using UFH. Recent studies have also shown that
      LMWHs are at least as effective and safe as UFH for the treatment of non-critical
      patients with pulmonary embolism. Whether or not home treatment of pulmonary
      embolism is feasible and safe remains to be demonstrated.

PMID- 10069767
TI  - Outpatient therapy with low-molecular-weight heparins: new perspectives for
      treatment of deep vein thrombosis.
AB  - Subcutaneous administration of low-molecular-weight heparin (LMWH) has been
      demonstrated to be as safe and effective for treatment of acute venous thrombosis
      as conventional treatment with unfractionated heparin, which requires intravenous
      infusion. In addition, LMWHs appear to provide an improved quality of life for
      patients with less impairment of physical activity. The ease of administration of
      LMWHs could be exploited in the clinical management of patients to increase the
      extent of LMWH outpatient therapy and reduce the number of hospitalizations for
      venous thrombosis, thus providing a more cost-effective therapy than conventional
      heparin. Efficient support services, patient education and careful follow up will
      be required for home treatment to be successful.

PMID- 10069768
TI  - New perspectives for treatment of pulmonary embolism.
AB  - Subcutaneous low-molecular-weight heparins (LMWHs) have been shown to be as safe
      and effective as intravenous unfractionated heparin (UFH) for the initial
      treatment of patients with deep vein thrombosis and acute symptomatic pulmonary
      embolism. In comparison with UFH, LMWHs have a longer half-life, greater
      bioavailability and more predictable antithrombotic effect when administered in
      fixed doses, thus obviating the need for laboratory monitoring. It is therefore
      feasible that LMWH preparations may replace UFH for the treatment of pulmonary
      embolism in the future. It is recommended that LMWH should be administered for 5
      10 days and should overlap with oral anticoagulant therapy by at least 4 days.
      Surgical pulmonary embolectomy should only be considered in patients with life
      threatening pulmonary embolism who have failed to respond during the first 3 h of
      thrombolytic therapy. The systematic use of vena cava filters is not recommended
      in patients presumed to be at high risk for pulmonary embolism.

PMID- 10069769
TI  - Out-of-hospital treatment of venous thrombosis: socioeconomic aspects and
      patients' quality of life.
AB  - Low-molecular-weight heparin has been recommended as the initial treatment of
      choice for patients with venous thromboembolism who require anticoagulant
      therapy. In recent studies, outpatient management of these patients has been
      proposed to be as effective and safe as treatment given in the hospital. This
      paper outlines the results of these studies and considers the feasibility of home
      treatment and the consequences of such a strategy. It is concluded that home
      treatment with low-molecular-weight heparin in patients with venous
      thromboembolism leads to significant benefits in terms of increase in the quality
      of life of the patients and a reduction in the duration of hospital stay, thus
      improving healthcare efficiency.

PMID- 10069770
TI  - Which endpoints to use in clinical trials in venous thromboembolism? Chairman's
      summary.

PMID- 10069771
TI  - Are symptomatic endpoints acceptable in venous thromboprophylactic studies?
AB  - Chemoprophylaxis with subcutaneous low-molecular-weight heparin has been shown to
      reduce deep vein thrombosis detected by surrogate endpoints such as fibrinogen
      scanning and venography. However, there have been few trials which have assessed
      clinical endpoints attributed to fatal and non-fatal pulmonary embolism following
      surgery. As these clinical endpoints are rare, large-scale trials using vascular
      mortality, vascular morbidity and the incidence of haemorrhage as clinical
      endpoints need to be performed to assess the efficacy of chemical
      thromboprophylaxis. The benefit of using clinical endpoints against the risk of
      haemorrhage should also be evaluated.

PMID- 10069772
TI  - What are the most reliable detection methods for deep vein thrombosis and
      pulmonary embolism to be used as endpoints in trials of venous
      thromboprophylaxis?
AB  - Numerous considerations and controversies attend the question of which endpoints
      to use in venous thromboembolism prophylaxis trials. In this paper, a rationale
      is presented for a new approach that simplifies certain aspects of endpoint
      detection in deep vein thrombosis and pulmonary embolism trials, and complicates
      others. The goal of this approach is to use reliably ascertainable endpoints that
      are clinically relevant and most probably predictive of clinical efficacy, in
      order to optimally inform the drug development process.

PMID- 10069773
TI  - Symptomatic endpoints for venous thromboembolism treatment.
AB  - Clinical trials evaluating antithrombotic therapy for the treatment of deep vein
      thrombosis require that the diagnosis is confirmed by objective testing prior to
      patient entry into the study. Two basic approaches may then be taken for defining
      endpoints to assess the efficacy of antithrombotic treatment. In the first
      approach, the diagnostic test is repeated at a predetermined time following the
      initiation of the interventional therapy. In the second approach, no further
      diagnostic testing is routinely performed for a minimum of 3 months following
      patient enrolment after the diagnosis of venous thromboembolism for evidence of
      symptomatic recurrent deep vein thrombosis or pulmonary embolism. This approach
      is used in later-phase clinical trials to examine whether a novel therapeutic
      agent is as safe and effective as the drugs currently used for management of
      venous thromboembolism. Symptomatic recurrent deep vein thrombosis and pulmonary
      embolism confirmed by objective testing are clinically important causes of
      patient morbidity, place patients at increased risk of fatal pulmonary embolism,
      cause increased rates of chronic thromboembolic complications and have resource
      consequences. Studies utilizing symptomatic recurrent deep vein thrombosis or
      pulmonary embolism as endpoints have been responsible for most of the treatment
      advances in the management of patients with venous thromboembolism that have been
      observed in the past 40 years. Although confirmation of recurrent venous
      thromboembolism is not possible in all patients, clinical trials using rigorous
      methodology can minimize the potential bias caused by the limitations of
      diagnostic test results. There is a need to develop better objective tests in the
      future, to distinguish previous from recurrent venous thromboembolism.

PMID- 10069774
TI  - Surrogate endpoints for the assessment of efficacy in venous thromboembolism
      treatment trials.
AB  - For the assessment of the efficacy of anticoagulant therapy in patients with
      symptomatic venous thrombosis, the incidence of symptomatic venous thromboembolic
      complications is the outcome measure of choice. However, the low incidence of
      such complications necessitates the inclusion of a prohibitively large number of
      patients in randomized trials evaluating anticoagulant regimens. Therefore,
      alternative efficacy outcome measures are desirable. This paper discusses the
      validity of the following alternative tests: venography and compression
      ultrasound for deep vein thrombosis; and pulmonary angiography and perfusion lung
      scanning for pulmonary embolism. It is concluded that a combination of one of the
      deep vein thrombosis tests and perfusion lung scanning is the optimal approach. A
      thrombotic burden assessment, using repeat venography and perfusion lung
      scanning, has been performed at the end of treatment (day 10) with low-molecular
      weight heparin and unfractionated heparin in 170 patients with symptomatic
      proximal deep vein thrombosis. An improved thrombotic burden was associated with
      a low number of subsequent symptomatic venous thromboembolic complications (4%),
      whereas this figure gradually increased for patients with an unchanged (10%) and
      deteriorated (29%) outcome (p < 0.005). It is concluded that the thrombotic
      burden assessment has potential to replace symptomatic outcomes, especially in
      dose-finding studies.

PMID- 10069775
TI  - Thromboembolic diseases: mechanisms, prophylaxis and treatment. Concluding
      remarks.

PMID- 10069776
TI  - Water quality objectives: yardsticks of the Great Lakes Water Quality Agreement.

PMID- 10069777
TI  - Meeting highlights. Highlights of the 20th congress of the European society of
      cardiology.

PMID- 10069778
TI  - Epidemic of cardiovascular disease and stroke: the three main challenges.
      Presented at the 71st scientific sessions of the American Heart Association.
      Dallas, Texas.

PMID- 10069779
TI  - Exercise training for heart failure: coming of age.

PMID- 10069780
TI  - Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.
AB  - BACKGROUND: Exposure to risk factors such as hypertension or hypercholesterolemia
      decreases the bioavailability of endothelium-derived nitric oxide (NO) and
      impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO
      synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in
      human plasma. The purpose of this study was to examine the relationship between
      plasma ADMA and atherosclerosis in humans. METHODS AND RESULTS: Subjects (n=116;
      age, 52+/-1 years; male:female ratio, 100:16) underwent a complete history and
      physical examination, determination of serum chemistries and ADMA levels, and
      duplex scanning of the carotid arteries. These individuals had no symptoms of
      coronary or peripheral artery disease and were taking no medications. Univariate
      and multivariate analyses revealed that plasma levels of ADMA were positively
      correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Sigma
      glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise
      regression analysis revealed that plasma ADMA levels were significantly
      correlated to the intima-media thickness of the carotid artery (as measured by
      high-resolution ultrasonography). CONCLUSIONS: This study reveals that plasma
      ADMA levels are positively correlated with risk factors for atherosclerosis.
      Furthermore, plasma ADMA level is significantly correlated with carotid intima
      media thickness. Our results suggest that this endogenous antagonist of NO
      synthase may be a marker of atherosclerosis.

PMID- 10069781
TI  - Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo.
AB  - BACKGROUND: The participation of endothelin-1 (ET-1) in the control of vascular
      tone in humans has been questioned, on the basis of the finding of subthreshold
      immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted
      abluminally, it might attain a higher concentration in the tunica media than in
      plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs)
      can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in
      the different layers of the wall of human arteries, including renal, gastric, and
      internal thoracic artery wall, obtained ex vivo from consenting patients with
      coronary artery disease and/or high blood pressure undergoing surgery, as well as
      from young organ donors. METHODS AND RESULTS: We performed immunohistochemistry
      with specific anti-ET-1 and anti-vWF antibodies followed by detection with an
      avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human
      endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse
      transcription-polymerase chain reaction in homogenates of vessel wall, including
      preparations deprived of both endothelium and adventitia, and in isolated VSMCs.
      We detected irET-1 in the endothelium of all arteries and in the tunica media of
      internal thoracic artery from most patients with coronary artery disease.
      PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these
      vessels. irET-1 and irvWF staining in endothelium and tunica media was measured
      by use of microscope-coupled computer-assisted technology. Significant
      correlations between the amount of irET-1 in the tunica media and mean blood
      pressure (P<0.05), total serum cholesterol (P<0.05), and number of
      atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was
      detectable almost exclusively in endothelial cells, whereas in patients with
      coronary artery disease and/or arterial hypertension, sizable amounts of irET-1
      were detectable in the tunica media of different types of arteries. In addition,
      VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes.
      CONCLUSIONS: Collectively, these findings are consistent with the contention that
      endothelial damage occurs in most patients with atherosclerosis and/or
      hypertension and that ET-1 is synthesized in VSMCs of these patients.

PMID- 10069782
TI  - Demonstration of rapid onset vascular endothelial dysfunction after
      hyperhomocysteinemia: an effect reversible with vitamin C therapy.
AB  - BACKGROUND: Hyperhomocysteinemia is a major and independent risk factor for
      vascular disease. The mechanisms by which homocysteine promotes atherosclerosis
      are not well understood. We hypothesized that elevated homocysteine
      concentrations are associated with rapid onset endothelial dysfunction, which is
      mediated through oxidant stress mechanisms and can be inhibited by the
      antioxidant vitamin C. METHODS AND RESULTS: We studied 17 healthy volunteers (10
      male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter
      responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN,
      endothelium independent) were measured with high resolution ultrasound at 0 hours
      (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100
      mg/kg), (2) oral methionine preceded by vitamin C (1g/day, for 1 week), and (3)
      placebo, on separate days and in random order. Plasma homocysteine increased (0
      hours, 12.8+/-1.4; 2 hours, 25.4+/-2.5; and 4 hours, 31. 2+/-3.1 micromol/l,
      P<0.001), and flow-mediated dilatation fell (0 hours, 4.3+/-0.7; 2 hours, 1.1+/
      0.9; and 4 hours, -0.7+/-0.8%) after oral L-methionine. There was an inverse
      linear relationship between homocysteine concentration and flow-mediated
      dilatation (P<0. 001). Pretreatment with vitamin C did not affect the rise in
      homocysteine concentrations after methionine (0 hours, 13.6+/-1.6; 2 hours,
      28.3+/-2.9; and 4 hours, 33.8+/-3.7 micromol/l, P=0.27), but did ameliorate the
      reduction in flow-mediated dilatation (0 hours, 4. 0+/-1.0; 2 hours, 3.5+/-1.2
      and 4 hours, 2.8+/-0.7%, P=0.02). GTN-induced endothelium independent brachial
      artery dilatation was not affected after methionine or methionine preceded by
      vitamin C. CONCLUSIONS: We conclude that an elevation in homocysteine
      concentration is associated with an acute impairment of vascular endothelial
      function that can be prevented by pretreatment with vitamin C in healthy
      subjects. Our results support the hypothesis that the adverse effects of
      homocysteine on vascular endothelial cells are mediated through oxidative stress
      mechanisms.

PMID- 10069783
TI  - Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future
      myocardial infarction.
AB  - BACKGROUND: Chlamydia pneumoniae has been hypothesized to play a role in
      atherothrombosis. However, prospective data relating exposure to Chlamydia
      pneumoniae and risks of future myocardial infarction (MI) are sparse. METHODS AND
      RESULTS: In a prospective cohort of nearly 15 000 healthy men, we measured IgG
      antibodies directed against Chlamydia pneumoniae in blood samples collected at
      baseline from 343 study participants who subsequently reported a first MI and
      from an equal number of age- and smoking-matched control subjects who did not
      report vascular disease during a 12-year follow-up period. The proportion of
      study subjects with IgG antibodies directed against Chlamydia increased with age
      and cigarette consumption. However, prevalence rates of Chlamydia IgG
      seropositivity were virtually identical at baseline among men who subsequently
      reported first MI compared with age- and smoking-matched control subjects.
      Specifically, the relative risks of future MI associated with Chlamydia
      pneumoniae IgG titers >/=1:16, 1:32, 1:64, 1:128, and 1:256 were 1.1, 1.0, 1.1,
      1.0, and 0.8, respectively (all probability values not significant). There was no
      association in analyses adjusted for other risk factors, evaluating early as
      compared with late events, or among nonsmokers. Further, there was no association
      between seropositivity and concentration of C-reactive protein, a marker of
      inflammation that predicts MI risk in this cohort. CONCLUSIONS: In a large-scale
      study of socioeconomically homogeneous men that controlled for age, smoking, and
      other cardiovascular risk factors, we found no evidence of association between
      Chlamydia pneumoniae IgG seropositivity and risks of future MI.

PMID- 10069784
TI  - Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective
      follow-up study of 14 786 middle-aged men and women in Finland.
AB  - BACKGROUND: Coronary heart disease (CHD) is markedly more common in men than in
      women. In both sexes, CHD risk increases with age, but the increase is sharper in
      women. We analyzed the extent to which major cardiovascular risk factors can
      explain the sex difference and the age-related increase in CHD risk. METHODS AND
      RESULTS: The study cohort consists of 14 786 Finnish men and women 25 to 64 years
      old at baseline. The following cardiovascular risk factors were determined:
      smoking, serum total cholesterol, HDL cholesterol, blood pressure, body mass
      index, and diabetes. Risk factor measurements were done in 1982 or 1987, and the
      cohorts were followed up until the end of 1994. The Cox proportional hazards
      model was used to assess the relation between risk factors and CHD risk. CHD
      incidence in men compared with women was approximately 3 times higher and
      mortality was approximately 5 times higher. Most of the risk factors were more
      favorable in women, but the sex difference in risk factor levels diminished with
      increasing age. Differences in risk factors between sexes, particularly in HDL
      cholesterol and smoking, explained nearly half of the difference in CHD risk
      between men and women. Differences in serum total cholesterol level, blood
      pressure, body mass index, and diabetes prevalence explained about one-third of
      the age-related increase in CHD risk among men and 50% to 60% among women.
      CONCLUSIONS: Differences in major cardiovascular risk factors explained a
      substantial part of the sex difference in CHD risk. An increase in risk factor
      levels was associated with the age-related increase in CHD incidence and
      mortality in both sexes but to a larger extent in women.

PMID- 10069785
TI  - Randomized, controlled trial of long-term moderate exercise training in chronic
      heart failure: effects on functional capacity, quality of life, and clinical
      outcome.
AB  - BACKGROUND: It is still a matter of debate whether exercise training (ET) is a
      beneficial treatment in chronic heart failure (CHF). METHODS AND RESULTS: To
      determine whether long-term moderate ET improves functional capacity and quality
      of life in patients with CHF and whether these effects translate into a favorable
      outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14
      years of age; 88 men and 11 women) were randomized into 2 groups. One group
      (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for
      8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not
      exercise. At baseline and at months 2 and 14, all patients underwent a
      cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group
      NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of
      life was assessed by questionnaire. Ninety-four patients completed the protocol
      (48 in group T and 46 in group NT). Changes were observed only in patients in
      group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18%
      and 24%, respectively; P<0. 001 for both) and did not change further after 1
      year. Quality of life also improved and paralleled peak VO2. Exercise training
      was associated both with lower mortality (n=9 versus n=20 for those with training
      versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and
      hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to
      0.88; P=0.02). Independent predictors of events were ventilatory threshold at
      baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta
      coefficient -0.165). CONCLUSIONS: Long-term moderate ET determines a sustained
      improvement in functional capacity and quality of life in patients with CHF. This
      benefit seems to translate into a favorable outcome.

PMID- 10069786
TI  - Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep
      apnea.
AB  - BACKGROUND: The chemoreflexes are an important mechanism for regulation of both
      breathing and autonomic cardiovascular function. Abnormalities in chemoreflex
      mechanisms may be implicated in increased cardiovascular stress in patients with
      obstructive sleep apnea (OSA). We tested the hypothesis that chemoreflex function
      is altered in patients with OSA. METHODS AND RESULTS: We compared ventilatory,
      sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia,
      and the cold pressor test in 16 untreated normotensive patients with OSA and 12
      normal control subjects matched for age and body mass index. Baseline muscle
      sympathetic nerve activity (MSNA) was higher in the patients with OSA than in the
      control subjects (43+/-4 versus 21+/-3 bursts per minute; P<0. 001). During
      hypoxia, patients with OSA had greater increases in minute ventilation (5.8+/-0.8
      versus 3.2+/-0.7 L/min; P=0.02), heart rate (10+/-1 versus 7+/-1 bpm; P=0.03),
      and mean arterial pressure (7+/-2 versus 0+/-2 mm Hg; P=0.001) than control
      subjects. Despite higher ventilation and blood pressure (both of which inhibit
      sympathetic activity) in OSA patients, the MSNA increase during hypoxia was
      similar in OSA patients and control subjects. When the sympathetic-inhibitory
      influence of breathing was eliminated by apnea during hypoxia, the increase in
      MSNA in OSA patients (106+/-20%) was greater than in control subjects (52+/-23%;
      P=0.04). Prolongation of R-R interval with apnea during hypoxia was also greater
      in OSA patients (24+/-6%) than in control subjects (7+/-5%) (P=0.04). Autonomic,
      ventilatory, and blood pressure responses to hypercapnia and the cold pressor
      test in OSA patients were not different from those observed in control subjects.
      CONCLUSIONS: OSA is associated with a selective potentiation of autonomic,
      hemodynamic, and ventilatory responses to peripheral chemoreceptor activation by
      hypoxia.

PMID- 10069787
TI  - Acute saline infusion reduces alveolar-capillary membrane conductance and
      increases airflow obstruction in patients with left ventricular dysfunction.
AB  - BACKGROUND: Impaired alveolar-capillary membrane conductance is the major cause
      for the reduction in pulmonary diffusing capacity for carbon monoxide (DLCO) in
      heart failure. Whether this reduction is fixed, reflecting pulmonary
      microvascular damage, or is variable is unknown. The aim of this study was to
      assess whether DLCO and its subdivisions, alveolar-capillary membrane conductance
      (DM) and pulmonary capillary blood volume (Vc), were sensitive to changes in
      intravascular volume. In addition, we examined the effects of volume loading on
      airflow rates. METHODS AND RESULTS: Ten patients with left ventricular
      dysfunction (LVD) and 8 healthy volunteers were studied. DM and Vc were
      determined by the Roughton and Forster method. The forced expiratory volume in 1
      second (FEV1), vital capacity, and peak expiratory flow rates (PEFR) were also
      recorded. In patients with LVD, infusion of 10 mL. kg-1 body wt of 0.9% saline
      acutely reduced DM (12.0+/-3.3 versus 10.4+/-3.5 mmol. min-1. kPa-1, P<0.005),
      FEV1 (2.3+/-0.4 versus 2.1+/-0.4 L, P<0.0005), and PEFR (446+/-55 versus 414+/-56
      L. min-1, P<0.005). All pulmonary function tests had returned to baseline values
      24 hours later. In normal subjects, saline infusion had no measurable effect on
      lung function. CONCLUSIONS: Acute intravascular volume expansion impairs alveolar
      capillary membrane function and increases airflow obstruction in patients with
      LVD but not in normal subjects. Thus, the abnormalities of pulmonary diffusion in
      heart failure, which were believed to be fixed, also have a variable component
      that could be amenable to therapeutic intervention.

PMID- 10069788
TI  - Vasodilator therapy for primary pulmonary hypertension in children.
AB  - BACKGROUND: This report presents 13 years of experience with vasodilator therapy
      for primary pulmonary hypertension (PPH) in children. Two eras were involved:
      between 1982 and 1987, oral calcium channel blockers were the only agents
      available for long-term therapy; after 1987, prostacyclin (PGI2) has been
      available for long-term intravenous use. METHODS AND RESULTS: Seventy-four
      children underwent short-term vasodilator testing with intravenous PGI2. Those
      who manifested pulmonary vasodilation ("acute responders") were treated with oral
      calcium channel blockers. Until 1987, "acute nonresponders" were treated in the
      same way as long as they had no serious side effects. When PGI2 became available
      for long-term administration, all nonresponders, as well as those who failed to
      improve clinically and hemodynamically on calcium channel blockers, were treated
      with long-term PGI2. In the 31 responders, calcium channel blockers improved
      survival compared with the 43 nonresponders (P=0.0002). Survival was also better
      in 24 PGI2-treated nonresponders compared with 22 nonresponders for whom PGI2 was
      unavailable (P=0.0005) as well as in all children who failed conventional therapy
      (n=31; P=0.002). CONCLUSIONS: Long-term vasodilator therapy improves survival in
      children with PPH. In acute responders, oral calcium channel blockers generally
      suffice. In both nonresponders to short-term testing and responders who fail to
      improve on calcium channel blockers, continuous intravenous infusion of PGI2
      improves survival.

PMID- 10069789
TI  - Prenatal features of ductus arteriosus constriction and restrictive foramen ovale
      in d-transposition of the great arteries.
AB  - BACKGROUND: Although most neonates with d-transposition of the great arteries
      (TGA) have an uncomplicated preoperative course, some with a restrictive foramen
      ovale (FO), ductus arteriosus (DA) constriction, or pulmonary hypertension may be
      severely hypoxemic and even die shortly after birth. Our goal was to determine
      whether prenatal echocardiography can identify these high-risk fetuses with TGA.
      METHODS AND RESULTS: We reviewed the prenatal and postnatal echocardiograms and
      outcomes of 16 fetuses with TGA/intact ventricular septum or small ventricular
      septal defect. Of the 16 fetuses, 6 prenatally had an abnormal FO (fixed
      position, flat, and/or redundant septum primum). Five of the 6 had restrictive FO
      at birth. Five fetuses had DA narrowing at the pulmonary artery end in utero, and
      6 had a small DA (diameter z score of <-2.0). Of 4 fetuses with the most
      diminutive DA, 2 also had an abnormal appearance of the FO, and both died
      immediately after birth. One other fetus had persistent pulmonary hypertension.
      Eight fetuses had abnormal Doppler flow pattern in the DA (continuous high
      velocity flow, n=1; retrograde diastolic flow, n=7). CONCLUSIONS: Abnormal
      features of the FO, DA, or both are present in fetuses with TGA at high risk for
      postnatal hypoxemia. These features may result from the abnormal intrauterine
      hemodynamics in TGA. A combination of restrictive FO and DA constriction in TGA
      may be associated with early neonatal death.

PMID- 10069790
TI  - Caval contribution to flow in the branch pulmonary arteries of Fontan patients
      with a novel application of magnetic resonance presaturation pulse.
AB  - BACKGROUND: A complete understanding of fluid mechanics in Fontan physiology
      includes knowledge of the caval contributions to right (RPA) and left (LPA)
      pulmonary arterial blood flow, total systemic venous return, and relative blood
      flow to each lung. METHODS AND RESULTS: Ten Fontan patients underwent cine MRI.
      Three cine scans of the pulmonary arteries were performed: (1) no presaturation
      pulse, (2) a presaturation pulse labeling inferior vena cava (IVC) blood (signal
      void), and (3) a presaturation pulse labeling superior vena cava (SVC) blood. The
      relative signal decrease is proportional to the amount of blood originating from
      the labeled vena cava. This method was validated in a phantom. Whereas 60+/-6% of
      SVC blood flowed into the RPA, 67+/-12% of IVC blood flowed toward the LPA. Of
      the blood in the LPA and RPA, 48+/-14% and 31+/-17%, respectively, came from the
      IVC. IVC blood contributed 40+/-16% to total systemic venous return. The
      distributions of blood to each lung were nearly equal (RPA/LPA blood=0.94+/-11).
      CONCLUSIONS: In Fontan patients with total cavopulmonary connection, SVC blood is
      directed toward the RPA and IVC blood is directed toward the LPA. Although the
      right lung volume is larger than the left, an equal amount of blood flow went to
      both lungs. LPA blood is composed of equal amounts of IVC and SVC blood because
      IVC contribution to total systemic venous return is smaller than that of the SVC.
      This technique and these findings can help to evaluate design changes of the
      systemic venous pathway to improve Fontan hemodynamics.

PMID- 10069791
TI  - Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice.
AB  - BACKGROUND: Iron deposition is evident in human atherosclerotic lesions,
      suggesting that iron may play a role in the development of atherosclerosis. To
      test this idea, the correlation between the extent of iron deposition and the
      severity of atherosclerosis in apolipoprotein E (apoE)-deficient mice was
      investigated. Furthermore, the effect of a low-iron diet on the progression of
      atherosclerotic lesions in these animals was evaluated. METHODS AND RESULTS: Iron
      deposition in tissues of apoE-deficient mice was examined by Perls' staining
      method. The results clearly demonstrated that iron deposits are present in
      atherosclerotic lesions and tissue sections of heart and liver in an age
      dependent manner. When the young mice received a low-iron diet for 3 months, the
      hematocrit, serum iron, hemoglobin, and cholesterol concentrations were not
      significantly altered compared with those of littermates placed on a chow diet.
      However, the serum ferritin level of animals in the iron-restricted group was 27%
      to 30% lower than that of the control group in either sex. Furthermore, the
      lipoproteins isolated from the iron-restricted group exhibited greater resistance
      to copper-induced oxidation. Histological examination revealed that
      atherosclerotic lesions developed in mice fed a low-iron diet were significantly
      smaller than those found in control littermates. Likewise, the iron deposition as
      well as tissue iron content was much less in aortic tissues of the iron
      restricted animals. Circulating autoantibodies to oxidized LDL and immunostains
      for epitopes of malondialdehyde-modified LDL detected on lesions were also
      significantly lower in mice fed a low-iron diet. CONCLUSIONS: Iron deposition is
      closely associated with the progression of atherosclerosis in apoE-deficient
      mice. Restriction in dietary iron intake leads to significant inhibition of
      lesion formation in these animals. These results suggest that the beneficial
      effect of a low-iron diet may be mediated, at least in part, by the reduction of
      iron deposition as well as LDL oxidation in vascular lesions.

PMID- 10069792
TI  - Homocysteine increases nitric oxide synthesis in cytokine-stimulated vascular
      smooth muscle cells.
AB  - BACKGROUND: Elevated plasma homocysteine levels have been reported to be an
      independent risk factor for vascular disease. However, there have been no reports
      concerning the effects of homocysteine on the production of nitric oxide (NO),
      another modulator of vascular function and proliferation, by the vascular smooth
      muscle. METHODS AND RESULTS: We investigated the effects of homocysteine on NO
      synthesis by measuring the production of nitrite, a stable metabolite of NO, in
      cultured rat vascular smooth muscle cells (VSMCs). Incubation of cultures with
      interleukin (IL)-1beta 10 ng/mL for 24 hours caused a significant increase in
      nitrite generation. The IL-1beta-induced nitrite production by VSMCs was
      significantly increased by homocysteine in a dose-dependent manner. This effect
      of homocysteine was significantly inhibited in the presence of NG-monomethyl-L
      arginine or actinomycin D. The homocysteine-induced nitrite production was
      accompanied by increased inducible NO synthase mRNA and protein accumulation.
      Cysteine, glutathione, or hydrogen peroxide also increased nitrite accumulation
      in IL-1beta-stimulated VSMCs. Coincubation with the radical scavenger catalase or
      superoxide dismutase markedly reduced homocysteine-induced nitrite accumulation.
      CONCLUSIONS: Homocysteine enhances NO synthesis in IL-1beta-stimulated VSMCs, and
      oxidative products are involved in the effect of homocysteine.

PMID- 10069793
TI  - Regression of atherosclerosis: role of nitric oxide and apoptosis.
AB  - BACKGROUND: We have recently found that administration of L-arginine to
      hypercholesterolemic rabbits induces regression of preexisting lesions. Others
      have previously shown that activation of the L-arginine/nitric oxide (NO)
      synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly,
      the current study was designed to determine if dietary supplementation of L
      arginine induces apoptosis of intimal lesions and if this effect is mediated
      through the NO synthase pathway. METHODS AND RESULTS: Male New Zealand White
      rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on
      2.5% L-arginine HCl in the drinking water, and the cholesterol diet was continued
      for 2 weeks, at which time the aortas were harvested for histological studies. L
      Arginine treatment increased the number of apoptotic cells (largely macrophages)
      in the intimal lesions by 3-fold (11.9+/-3.9 vs 3.9+/-1. 4 apoptotic cells/mm2,
      P<0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic
      segments were incubated in cell culture medium for 4 to 24 hours with modulators
      of the NO synthase pathway. The tissues were then collected for histological
      studies and the conditioned medium collected for measurement of nitrogen oxides
      by chemiluminescence. Addition of sodium nitroprusside (10(-5) mol/L) to the
      medium caused a time-dependent increase in apoptosis of vascular cells (largely
      macrophages) in the intimal lesion. L-Arginine (10(-3) mol/L) had an identical
      effect on apoptosis, which was associated with an increase in nitrogen oxides
      released into the medium. These effects were not mimicked by D-arginine, and they
      were antagonized by the NO synthase inhibitor L-nitro-arginine (10(-4) mol/L).
      The effect of L-arginine was not influenced by an antagonist of cGMP-dependent
      protein kinase, nor was the effect mimicked by the agonist of protein kinase G or
      8-BR cGMP. CONCLUSIONS: These results indicate that supplemental L-arginine
      induces apoptosis of macrophages in intimal lesions by its metabolism to NO,
      which acts through a cGMP-independent pathway. These studies are consistent with
      our previous observation that supplementation of dietary arginine induces
      regression of atheroma in this animal model. These studies provide a rationale
      for further investigation of the therapeutic potential of manipulating the NO
      synthase pathway in atherosclerosis.

PMID- 10069794
TI  - Effects of hypertension, diabetes mellitus, and hypercholesterolemia on
      endothelin type B receptor-mediated nitric oxide release from rat kidney.
AB  - BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide,
      stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in
      vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in
      pathological conditions are largely unknown. METHODS AND RESULTS: We studied the
      effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance
      and nitric oxide (NO) release in the isolated, perfused kidney of rats with
      hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry
      of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at
      concentrations of </=10(-10) mol/L reduced renal perfusion pressure in Dahl salt
      resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive
      (S) rats (10(-10) mol/L: -10.3+/-0. 6% versus 11.2+/-1.5%, R versus S; P<0.01).
      BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the
      level of NO release in S rats was lower, as detected by chemiluminescence (10(
      10) mol/L: 10.7+/-0.7 versus 3.1+/-0.4 fmol/min per gram of kidney, R versus S;
      P<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced
      diabetic rats and diet-induced hypercholesterolemic rats. Expression of
      endothelial NO synthase decreased in S rats but not in diabetic or
      hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was
      decreased in all 3 disease models compared with that in the vascular smooth
      muscle cell. CONCLUSIONS: These results suggest that impaired NO release in
      response to stimulation of ETBR is due, at least in part, to a decrease in
      endothelial ETBR and may play a role in vascular dysfunction usually associated
      with arteriosclerosis-related diseases.

PMID- 10069795
TI  - Preconditioning in immature rabbit hearts: role of KATP channels.
AB  - BACKGROUND: The protective effects of ischemic preconditioning have been shown to
      occur in adult hearts of all species studied. We determined whether immature
      hearts normoxic or chronically hypoxic from birth could be preconditioned, the
      time window or memory of the cardioprotective effect, and the involvement of the
      KATP channel. METHODS AND RESULTS: Isolated immature rabbit hearts (7 to 10 days
      old) were subjected to 0, 1, or 3 cycles of preconditioning consisting of 5
      minutes of global ischemia plus 10 minutes of reperfusion. This was followed by
      30 minutes of global ischemia and 35 minutes of reperfusion. Normoxic hearts
      (FIO2=0.21) subjected to 1 cycle of preconditioning recovered 70+/-7% of left
      ventricular developed pressure compared with 43+/-8% recovery in
      nonpreconditioned controls. Three cycles of preconditioning did not result in
      additional recovery (63+/-8%). Hearts from rabbits raised from birth in hypoxic
      conditions (FIO2=0.12) and subjected to 1 and 3 preconditioning cycles did not
      show increased recovery (68+/-8% and 65+/-5%) compared with nonpreconditioned
      hypoxic controls (63+/-9%), although the recovery was greater in chronically
      hypoxic hearts than in age-matched normoxic controls. Increasing the recovery
      period after the preconditioning stimulus from 10 to 30 minutes resulted in a
      loss of cardioprotection. Pretreatment of normoxic hearts for 30 minutes with the
      KATP channel blocker 5-hydroxydecanoate (300 micromol/L) completely abolished
      preconditioning (70+/-7% to 35+/-9%) but had no effect on nonpreconditioned
      hearts (40+/-8%). CONCLUSIONS: Immature hearts normoxic from birth can be
      preconditioned, whereas immature hearts hypoxic from birth cannot.
      Preconditioning in normoxic immature hearts is associated with activation of the
      KATP channel.

PMID- 10069796
TI  - Regional differences in the recovery course of tachycardia-induced changes of
      atrial electrophysiological properties.
AB  - BACKGROUND: Regional differences in recovery of tachycardia-induced changes of
      atrial electrophysiological properties have not been well studied. METHODS AND
      RESULTS: In the control group (5 dogs), atrial effective refractory period (AERP)
      and inducibility of atrial fibrillation (AF) were assessed before and every 4
      hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8
      week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF
      were assessed before and after complete AVJ ablation with 8-week rapid right
      atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs),
      AERP and inducibility of AF were assessed before and after 8-week rapid left
      atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were
      obtained from 7 epicardial sites. In the control group, atrial
      electrophysiological properties obtained immediately and during 48-hour
      measurements after pacing did not show any change. In the 2 experimental groups,
      recovery of atrial electrophysiological properties included a progressive
      recovery of AERP shortening, recovery of AERP maladaptation, and decrease of
      duration and episodes of reinduced AF. However, recovery of shortening and
      maladaptation of AERP and inducibility of AF was slower at the LA than at the RA
      and Bachmann's bundle. CONCLUSIONS: The LA had a slower recovery of tachycardia
      induced changes of atrial electrophysiological properties, and this might play a
      critical role in initiation of AF.

PMID- 10069797
TI  - Digitalis.
AB  - Cardiac glycosides have played a prominent role in the therapy of congestive
      heart failure since William Withering codified their use in his late 18th century
      monograph on the efficacy of the leaves of the common foxglove plant (Digitalis
      purpurea). Despite their widespread acceptance into medical practice in the
      ensuing 200 years, both the efficacy and the safety of this class of drugs
      continue to be a topic of debate. Moreover, despite the fact that the molecular
      target for the cardiac glycosides, the alpha-subunit of sarcolemmal Na+K+-ATPase
      (or sodium pump) found on most eukaryotic cell membranes, has been known for
      several decades, it remains controversial whether the sympatholytic or positive
      inotropic effects of these agents is the mechanism most relevant to relief of
      heart failure symptoms in humans with systolic ventricular dysfunction. Herein,
      we review the molecular and clinical pharmacology of this venerable class of
      drugs, as well as the manifestations of digitalis toxicity and their treatment.
      We also review in some detail recent clinical trials designed to examine the
      efficacy of these drugs in heart failure, with a focus on the Digoxin
      Investigation Group data set. Although, in our opinion, the data on balance
      warrant the continued use of these drugs for the treatment of symptoms of heart
      failure in patients already receiving contemporary multidrug therapy for this
      disease, the use of digitalis preparations will inevitably decline with the
      maturation of newer pharmacotherapies.

PMID- 10069798
TI  - Images in cardiovascular medicine. Roth's spots.

PMID- 10069799
TI  - Revascularization after myocardial infarction.

PMID- 10069800
TI  - Infrequent translation of a nonsense codon is sufficient to decrease mRNA level.
AB  - In many organisms nonsense mutations decrease the level of mRNA. In the case of
      mammalian cells, it is still controversial whether translation is required for
      this nonsense-mediated RNA decrease (NMD). Although previous analyzes have shown
      that conditions that impede translation termination at nonsense codons also
      prevent NMD, the residual level of termination was unknown in these experiments.
      Moreover, the conditions used to impede termination might also have interfered
      with NMD in other ways. Because of these uncertainties, we have tested the
      effects of limiting translation of a nonsense codon in a different way, using two
      mutations in the immunoglobulin mu heavy chain gene. For this purpose we
      exploited an exceptional nonsense mutation at codon 3, which efficiently
      terminates translation but nonetheless maintains a high level of mu mRNA. We have
      shown 1) that translation of Ter462 in the double mutant occurs at only
      approximately 4% the normal frequency, and 2) that Ter462 in cis with Ter3 can
      induce NMD. That is, translation of Ter462 at this low (4%) frequency is
      sufficient to induce NMD.

PMID- 10069801
TI  - Phosphorylation of tyrosine 992, 1068, and 1086 is required for conformational
      change of the human epidermal growth factor receptor c-terminal tail.
AB  - We reported previously that a conformation-specific antibody, Ab P2, to a 16
      amino acid peptide (Glu-Gly-Tyr-Lys-Lys-Lys-Tyr-Gln-Gln-Val-Asp-Glu-Glu-Phe-Leu
      Arg) of the cytoplasmic domain of the beta-type platelet-derived growth factor
      receptor also recognizes the epidermal growth factor (EGF) receptor. Although the
      antibody is not directed to phosphotyrosine, it recognizes in immunoprecipitation
      the activated and hence phosphorylated form of both receptors. In P2 peptide,
      there are two tripeptide sequences, Asp-Glu-Glu and Tyr-Gln-Gln, that are also
      present in the EGF receptor. Our present studies using either EGF receptor C
      terminal deletion mutants or point mutations (Tyr-->Phe) and our previous studies
      on antibody inhibition by P2-derived peptides suggest that Gln-Gln in combination
      with Asp-Glu-Glu forms a high-affinity complex with Ab P2 and that such complex
      formation is dependent on tyrosine phosphorylation. Of the five phosphate
      acceptor sites in the EGF receptor, clustered in the extreme C-terminal tail,
      phosphorylation of three tyrosine residues (992, 1068, and 1086) located between
      Asp-Glu-Glu and Gln-Gln is necessary for Ab P2 binding. In contrast, the acceptor
      sites Tyr 1173 and 1148 play no role in the conformation change. Asp-Glu-Glu and
      Gln-Gln are located 169 amino acids apart, and it is highly likely that the
      interactions among three negatively charged phosphotyrosine residues in the
      receptor C terminus may result in the bending of the peptide chain in such a way
      that these two peptides come close to each other to form an antibody-binding
      site. Such a possibility is also supported by our finding that receptor
      dephosphorylation results in complete loss of Ab P2-binding activity. In
      conclusion, we have identified a domain within the cytoplasmic part of the EGF
      receptor whose conformation is altered by receptor phosphorylation; furthermore,
      we have identified the tyrosine residues that positively regulate this
      conformation.

PMID- 10069802
TI  - High-affinity binding of the AP-1 adaptor complex to trans-golgi network
      membranes devoid of mannose 6-phosphate receptors.
AB  - The GTP-binding protein ADP-ribosylation factor (ARF) initiates clathrin-coat
      assembly at the trans-Goli network (TGN) by generating high-affinity membrane
      binding sites for the AP-1 adaptor complex. Both transmembrane proteins, which
      are sorted into the assembling coated bud, and novel docking proteins have been
      suggested to be partners with GTP-bound ARF in generating the AP-1-docking sites.
      The best characterized, and probably the major transmembrane molecules sorted
      into the clathrin-coated vesicles that form on the TGN, are the mannose 6
      phosphate receptors (MPRs). Here, we have examined the role of the MPRs in the AP
      1 recruitment process by comparing fibroblasts derived from embryos of either
      normal or MPR-negative animals. Despite major alterations to the lysosome
      compartment in the MPR-deficient cells, the steady-state distribution of AP-1 at
      the TGN is comparable to that of normal cells. Golgi-enriched membranes prepared
      from the receptor-negative cells also display an apparently normal capacity to
      recruit AP-1 in vitro in the presence of ARF and either GTP or GTPgammaS. The AP
      1 adaptor is recruited specifically onto the TGN and not onto the numerous
      abnormal membrane elements that accumulate within the MPR-negative fibroblasts.
      AP-1 bound to TGN membranes from either normal or MPR-negative fibroblasts is
      fully resistant to chemical extraction with 1 M Tris-HCl, pH 7, indicating that
      the adaptor binds to both membrane types with high affinity. The only difference
      we do note between the Golgi prepared from the MPR-deficient cells and the normal
      cells is that AP-1 recruited onto the receptor-lacking membranes in the presence
      of ARF1.GTP is consistently more resistant to extraction with Tris. Because
      sensitivity to Tris extraction correlates well with nucleotide hydrolysis, this
      finding might suggest a possible link between MPR sorting and ARF GAP regulation.
      We conclude that the MPRs are not essential determinants in the initial steps of
      AP-1 binding to the TGN but, instead, they may play a regulatory role in clathrin
      coated vesicle formation by affecting ARF.GTP hydrolysis.

PMID- 10069803
TI  - The multisubstrate docking site of the MET receptor is dispensable for MET
      mediated RAS signaling and cell scattering.
AB  - The scatter factor/hepatocyte growth factor regulates scattering and
      morphogenesis of epithelial cells through activation of the MET tyrosine kinase
      receptor. In particular, the noncatalytic C-terminal tail of MET contains two
      autophosphorylation tyrosine residues, which form a multisubstrate-binding site
      for several cytoplasmic effectors and are thought to be essential for signal
      transduction. We show here that a MET receptor mutated on the four C-terminal
      tyrosine residues, Y1311F, Y1347F, Y1354F, and Y1363F, can induce efficiently a
      transcriptional response and cell scattering, whereas it cannot induce cell
      morphogenesis. Although the mutated receptor had lost its ability to recruit
      and/or activate known signaling molecules, such as GRB2, SHC, GAB1, and PI3K, by
      using a sensitive association-kinase assay we found that the mutated receptor can
      still associate and phosphorylate a approximately 250-kDa protein. By further
      examining signal transduction mediated by the mutated MET receptor, we
      established that it can transmit efficient RAS signaling and that cell scattering
      by the mutated MET receptor could be inhibited by a pharmacological inhibitor of
      the MEK-ERK (MAP kinase kinase-extracellular signal-regulated kinase) pathway. We
      propose that signal transduction by autophosphorylation of the C-terminal
      tyrosine residues is not the sole mechanism by which the activated MET receptor
      can transmit RAS signaling and cell scattering.

PMID- 10069804
TI  - OBA/Ku86: DNA binding specificity and involvement in mammalian DNA replication.
AB  - Ors-binding activity (OBA) was previously semipurified from HeLa cells through
      its ability to interact specifically with the 186-basepair (bp) minimal
      replication origin of ors8 and support ors8 replication in vitro. Here, through
      competition band-shift analyses, using as competitors various subfragments of the
      186-bp minimal ori, we identified an internal region of 59 bp that competed for
      OBA binding as efficiently as the full 186-bp fragment. The 59-bp fragment has
      homology to a 36-bp sequence (A3/4) generated by comparing various mammalian
      replication origins, including the ors. A3/4 is, by itself, capable of competing
      most efficiently for OBA binding to the 186-bp fragment. Band-shift elution of
      the A3/4-OBA complex, followed by Southwestern analysis using the A3/4 sequence
      as probe, revealed a major band of approximately 92 kDa involved in the DNA
      binding activity of OBA. Microsequencing analysis revealed that the 92-kDa
      polypeptide is identical to the 86-kDa subunit of human Ku antigen. The affinity
      purified OBA fraction obtained using an A3/4 affinity column also contained the
      70-kDa subunit of Ku and the DNA-dependent protein kinase catalytic subunit. In
      vitro DNA replication experiments in the presence of A3/4 oligonucleotide or anti
      Ku70 and anti-Ku86 antibodies implicate Ku in mammalian DNA replication.

PMID- 10069805
TI  - GCS1, an Arf guanosine triphosphatase-activating protein in Saccharomyces
      cerevisiae, is required for normal actin cytoskeletal organization in vivo and
      stimulates actin polymerization in vitro.
AB  - Recent cloning of a rat brain phosphatidylinositol 3,4, 5-trisphosphate binding
      protein, centaurin alpha, identified a novel gene family based on homology to an
      amino-terminal zinc-binding domain. In Saccharomyces cerevisiae, the protein with
      the highest homology to centaurin alpha is Gcs1p, the product of the GCS1 gene.
      GCS1 was originally identified as a gene conditionally required for the reentry
      of cells into the cell cycle after stationary phase growth. Gcs1p was previously
      characterized as a guanosine triphosphatase-activating protein for the small
      guanosine triphosphatase Arf1, and gcs1 mutants displayed vesicle-trafficking
      defects. Here, we have shown that similar to centaurin alpha, recombinant Gcs1p
      bound phosphoinositide-based affinity resins with high affinity and specificity.
      A novel GCS1 disruption strain (gcs1Delta) exhibited morphological defects, as
      well as mislocalization of cortical actin patches. gcs1Delta was hypersensitive
      to the actin monomer-sequestering drug, latrunculin-B. Synthetic lethality was
      observed between null alleles of GCS1 and SLA2, the gene encoding a protein
      involved in stabilization of the actin cytoskeleton. In addition, synthetic
      growth defects were observed between null alleles of GCS1 and SAC6, the gene
      encoding the yeast fimbrin homologue. Recombinant Gcs1p bound to actin filaments,
      stimulated actin polymerization, and inhibited actin depolymerization in vitro.
      These data provide in vivo and in vitro evidence that Gcs1p interacts directly
      with the actin cytoskeleton in S. cerevisiae.

PMID- 10069806
TI  - Mutations at phosphorylation sites of Xenopus microtubule-associated protein 4
      affect its microtubule-binding ability and chromosome movement during mitosis.
AB  - Microtubule-associated proteins (MAPs) bind to and stabilize microtubules (MTs)
      both in vitro and in vivo and are thought to regulate MT dynamics during the cell
      cycle. It is known that p220, a major MAP of Xenopus, is phosphorylated by
      p34(cdc2) kinase as well as MAP kinase in mitotic cells, and that the
      phosphorylated p220 loses its MT-binding and -stabilizing abilities in vitro. We
      cloned a full-length cDNA encoding p220, which identified p220 as a Xenopus
      homologue of MAP4 (XMAP4). To examine the physiological relevance of XMAP4
      phosphorylation in vivo, Xenopus A6 cells were transfected with cDNAs encoding
      wild-type or various XMAP4 mutants fused with a green fluorescent protein.
      Mutations of serine and threonine residues at p34(cdc2) kinase-specific
      phosphorylation sites to alanine interfered with mitosis-associated reduction in
      MT affinity of XMAP4, and their overexpression affected chromosome movement
      during anaphase A. These findings indicated that phosphorylation of XMAP4
      (probably by p34(cdc2) kinase) is responsible for the decrease in its MT-binding
      and -stabilizing abilities during mitosis, which are important for chromosome
      movement during anaphase A.

PMID- 10069807
TI  - Genetic interactions between KAR7/SEC71, KAR8/JEM1, KAR5, and KAR2 during nuclear
      fusion in Saccharomyces cerevisiae.
AB  - During mating of Saccharomyces cerevisiae, two nuclei fuse to produce a single
      diploid nucleus. Two genes, KAR7 and KAR8, were previously identified by
      mutations that cause defects in nuclear membrane fusion. KAR7 is allelic to
      SEC71, a gene involved in protein translocation into the endoplasmic reticulum.
      Two other translocation mutants, sec63-1 and sec72Delta, also exhibited moderate
      karyogamy defects. Membranes from kar7/sec71Delta and sec72Delta, but not sec63
      1, exhibited reduced membrane fusion in vitro, but only at elevated temperatures.
      Genetic interactions between kar7 and kar5 mutations were suggestive of protein
      protein interactions. Moreover, in sec71 mutants, Kar5p was absent from the SPB
      and was not detected by Western blot or immunoprecipitation of pulse-labeled
      protein. KAR8 is allelic to JEMI, encoding an endoplasmic reticulum resident DnaJ
      protein required for nuclear fusion. Overexpression of KAR8/JEM1 (but not SEC63)
      strongly suppressed the mating defect of kar2-1, suggesting that Kar2p interacts
      with Kar8/Jem1p for nuclear fusion. Electron microscopy analysis of kar8 mutant
      zygotes revealed a nuclear fusion defect different from kar2, kar5, and
      kar7/sec71 mutants. Analysis of double mutants suggested that Kar5p acts before
      Kar8/Jem1p. We propose the existence of a nuclear envelope fusion chaperone
      complex in which Kar2p, Kar5p, and Kar8/Jem1p are key components and Sec71p and
      Sec72p play auxiliary roles.

PMID- 10069808
TI  - MCD4 encodes a conserved endoplasmic reticulum membrane protein essential for
      glycosylphosphatidylinositol anchor synthesis in yeast.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are cell surface-localized
      proteins that serve many important cellular functions. The pathway mediating
      synthesis and attachment of the GPI anchor to these proteins in eukaryotic cells
      is complex, highly conserved, and plays a critical role in the proper targeting,
      transport, and function of all GPI-anchored protein family members. In this
      article, we demonstrate that MCD4, an essential gene that was initially
      identified in a genetic screen to isolate Saccharomyces cerevisiae mutants
      defective for bud emergence, encodes a previously unidentified component of the
      GPI anchor synthesis pathway. Mcd4p is a multimembrane-spanning protein that
      localizes to the endoplasmic reticulum (ER) and contains a large NH2-terminal ER
      lumenal domain. We have also cloned the human MCD4 gene and found that Mcd4p is
      both highly conserved throughout eukaryotes and has two yeast homologues. Mcd4p's
      lumenal domain contains three conserved motifs found in mammalian
      phosphodiesterases and nucleotide pyrophosphases; notably, the temperature
      conditional MCD4 allele used for our studies (mcd4-174) harbors a single amino
      acid change in motif 2. The mcd4-174 mutant (1) is defective in ER-to-Golgi
      transport of GPI-anchored proteins (i.e., Gas1p) while other proteins (i.e., CPY)
      are unaffected; (2) secretes and releases (potentially up-regulated cell wall)
      proteins into the medium, suggesting a defect in cell wall integrity; and (3)
      exhibits marked morphological defects, most notably the accumulation of
      distorted, ER- and vesicle-like membranes. mcd4-174 cells synthesize all classes
      of inositolphosphoceramides, indicating that the GPI protein transport block is
      not due to deficient ceramide synthesis. However, mcd4-174 cells have a severe
      defect in incorporation of [3H]inositol into proteins and accumulate several
      previously uncharacterized [3H]inositol-labeled lipids whose properties are
      consistent with their being GPI precursors. Together, these studies demonstrate
      that MCD4 encodes a new, conserved component of the GPI anchor synthesis pathway
      and highlight the intimate connections between GPI anchoring, bud emergence, cell
      wall function, and feedback mechanisms likely to be involved in regulating each
      of these essential processes. A putative role for Mcd4p as participating in the
      modification of GPI anchors with side chain phosphoethanolamine is also
      discussed.

PMID- 10069810
TI  - The DNA helicase activity of BLM is necessary for the correction of the genomic
      instability of bloom syndrome cells.
AB  - Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by
      growth deficiency, immunodeficiency, genomic instability, and the early
      development of cancers of many types. BLM, the protein encoded by BLM, the gene
      mutated in BS, is localized in nuclear foci and absent from BS cells. BLM encodes
      a DNA helicase, and proteins from three missense alleles lack displacement
      activity. BLM transfected into BS cells reduces the frequency of sister chromatid
      exchanges and restores BLM in the nucleus. Missense alleles fail to reduce the
      sister chromatid exchanges in transfected BS cells or restore the normal nuclear
      pattern. BLM complements a phenotype of a Saccharomyces cerevisiae sgs1 top3
      strain, and the missense alleles do not. This work demonstrates the importance of
      the enzymatic activity of BLM for its function and nuclear localization pattern.

PMID- 10069809
TI  - The nucleoporin nup153 plays a critical role in multiple types of nuclear export.
AB  - The fundamental process of nucleocytoplasmic transport takes place through the
      nuclear pore. Peripheral pore structures are presumably poised to interact with
      transport receptors and their cargo as these receptor complexes first encounter
      the pore. One such peripheral structure likely to play an important role in
      nuclear export is the basket structure located on the nuclear side of the pore.
      At present, Nup153 is the only nucleoporin known to localize to the surface of
      this basket, suggesting that Nup153 is potentially one of the first pore
      components an RNA or protein encounters during export. In this study, anti-Nup153
      antibodies were used to probe the role of Nup153 in nuclear export in Xenopus
      oocytes. We found that Nup153 antibodies block three major classes of RNA export,
      that of snRNA, mRNA, and 5S rRNA. Nup153 antibodies also block the NES protein
      export pathway, specifically the export of the HIV Rev protein, as well as Rev
      dependent RNA export. Not all export was blocked; Nup153 antibodies did not
      impede the export of tRNA or the recycling of importin beta to the cytoplasm. The
      specific antibodies used here also did not affect nuclear import, whether
      mediated by importin alpha/beta or by transportin. Overall, the results indicate
      that Nup153 is crucial to multiple classes of RNA and protein export, being
      involved at a vital juncture point in their export pathways. This juncture point
      appears to be one that is bypassed by tRNA during its export. We asked whether a
      physical interaction between RNA and Nup153 could be observed, using
      homoribopolymers as sequence-independent probes for interaction. Nup153, unlike
      four other nucleoporins including Nup98, associated strongly with poly(G) and
      significantly with poly(U). Thus, Nup153 is unique among the nucleoporins tested
      in its ability to interact with RNA and must do so either directly or indirectly
      through an adaptor protein. These results suggest a unique mechanistic role for
      Nup153 in the export of multiple cargos.

PMID- 10069811
TI  - Cluster of differentiation antigen 4 (CD4) endocytosis and adaptor complex
      binding require activation of the CD4 endocytosis signal by serine
      phosphorylation.
AB  - Cluster of differentiation antigen 4 (CD4), the T lymphocyte antigen receptor
      component and human immunodeficiency virus coreceptor, is down-modulated when
      cells are activated by antigen or phorbol esters. During down-modulation CD4
      dissociates from p56(lck), undergoes endocytosis through clathrin-coated pits,
      and is then sorted in early endosomes to late endocytic organelles where it is
      degraded. Previous studies have suggested that phosphorylation and a dileucine
      sequence are required for down-modulation. Using transfected HeLa cells, in which
      CD4 endocytosis can be studied in the absence of p56(lck), we show that the
      dileucine sequence in the cytoplasmic domain is essential for clathrin-mediated
      CD4 endocytosis. However, this sequence is only functional as an endocytosis
      signal when neighboring serine residues are phosphorylated. Phosphoserine is
      required for rapid endocytosis because CD4 molecules in which the cytoplasmic
      domain serine residues are substituted with glutamic acid residues are not
      internalized efficiently. Using surface plasmon resonance, we show that CD4
      peptides containing the dileucine sequence bind weakly to clathrin adaptor
      protein complexes 2 and 1. The affinity of this interaction is increased 350- to
      700-fold when the peptides also contain phosphoserine residues.

PMID- 10069812
TI  - Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in
      Chlamydomonas.
AB  - A second cytoplasmic dynein heavy chain (cDhc) has recently been identified in
      several organisms, and its expression pattern is consistent with a possible role
      in axoneme assembly. We have used a genetic approach to ask whether cDhc1b is
      involved in flagellar assembly in Chlamydomonas. Using a modified PCR protocol,
      we recovered two cDhc sequences distinct from the axonemal Dhc sequences
      identified previously. cDhc1a is closely related to the major cytoplasmic Dhc,
      whereas cDhc1b is closely related to the minor cDhc isoform identified in sea
      urchins, Caenorhabditis elegans, and Tetrahymena. The Chlamydomonas cDhc1b
      transcript is a low-abundance mRNA whose expression is enhanced by
      deflagellation. To determine its role in flagellar assembly, we screened a
      collection of stumpy flagellar (stf) mutants generated by insertional mutagenesis
      and identified two strains in which portions of the cDhc1b gene have been
      deleted. The two mutants assemble short flagellar stumps (<1-2 micrometer) filled
      with aberrant microtubules, raft-like particles, and other amorphous material.
      The results indicate that cDhc1b is involved in the transport of components
      required for flagellar assembly in Chlamydomonas.

PMID- 10069813
TI  - A modulatory role for clathrin light chain phosphorylation in Golgi membrane
      protein localization during vegetative growth and during the mating response of
      Saccharomyces cerevisiae.
AB  - The role of clathrin light chain phosphorylation in regulating clathrin function
      has been examined in Saccharomyces cerevisiae. The phosphorylation state of yeast
      clathrin light chain (Clc1p) in vivo was monitored by [32P]phosphate labeling and
      immunoprecipitation. Clc1p was phosphorylated in growing cells and also
      hyperphosphorylated upon activation of the mating response signal transduction
      pathway. Mating pheromone-stimulated hyperphosphorylation of Clc1p was dependent
      on the mating response signal transduction pathway MAP kinase Fus3p. Both basal
      and stimulated phosphorylation occurred exclusively on serines. Mutagenesis of
      Clc1p was used to map major phosphorylation sites to serines 52 and 112, but
      conversion of all 14 serines in Clc1p to alanines [S(all)A] was necessary to
      eliminate phosphorylation. Cells expressing the S(all)A mutant Clc1p displayed no
      defects in Clc1p binding to clathrin heavy chain, clathrin trimer stability,
      sorting of a soluble vacuolar protein, or receptor-mediated endocytosis of mating
      pheromone. However, the trans-Golgi network membrane protein Kex2p was not
      optimally localized in mutant cells. Furthermore, pheromone treatment exacerbated
      the Kex2p localization defect and caused a corresponding defect in Kex2p-mediated
      maturation of the alpha-factor precursor. The results reveal a novel requirement
      for clathrin during the mating response and suggest that phosphorylation of the
      light chain subunit modulates the activity of clathrin at the trans-Golgi
      network.

PMID- 10069814
TI  - The development of cell processes induced by tau protein requires phosphorylation
      of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in
      the proline-rich domains.
AB  - The differentiation of neurons and the outgrowth of neurites depends on
      microtubule-associated proteins such as tau protein. To study this process, we
      have used the model of Sf9 cells, which allows efficient transfection with
      microtubule-associated proteins (via baculovirus vectors) and observation of the
      resulting neurite-like extensions. We compared the phosphorylation of tau23 (the
      embryonic form of human tau) with mutants in which critical phosphorylation sites
      were deleted by mutating Ser or Thr residues into Ala. One can broadly
      distinguish two types of sites, the KXGS motifs in the repeats (which regulate
      the affinity of tau to microtubules) and the SP or TP motifs in the domains
      flanking the repeats (which contain epitopes for antibodies diagnostic of
      Alzheimer's disease). Here we report that both types of sites can be
      phosphorylated by endogenous kinases of Sf9 cells, and that the phosphorylation
      pattern of the transfected tau is very similar to that of neurons, showing that
      Sf9 cells can be regarded as an approximate model for the neuronal balance
      between kinases and phosphatases. We show that mutations in the repeat domain and
      in the flanking domains have opposite effects. Mutations of KXGS motifs in the
      repeats (Ser262, 324, and 356) strongly inhibit the outgrowth of cell extensions
      induced by tau, even though this type of phosphorylation accounts for only a
      minor fraction of the total phosphate. This argues that the temporary detachment
      of tau from microtubules (by phosphorylation at KXGS motifs) is a necessary
      condition for establishing cell polarity at a critical point in space or time.
      Conversely, the phosphorylation at SP or TP motifs represents the majority of
      phosphate (>80%); mutations in these motifs cause an increase in cell extensions,
      indicating that this type of phosphorylation retards the differentiation of the
      cells.

PMID- 10069815
TI  - Interaction of the Doa4 deubiquitinating enzyme with the yeast 26S proteasome.
AB  - e Saccharomyces cerevisiae Doa4 deubiquitinating enzyme is required for the rapid
      degradation of protein substrates of the ubiquitin-proteasome pathway. Previous
      work suggested that Doa4 functions late in the pathway, possibly by
      deubiquitinating (poly)-ubiquitin-substrate intermediates associated with the 26S
      proteasome. We now provide evidence for physical and functional interaction
      between Doa4 and the proteasome. Genetic interaction is indicated by the mutual
      enhancement of defects associated with a deletion of DOA4 or a proteasome
      mutation when the two mutations are combined. Physical association of Doa4 and
      the proteasome was investigated with a new yeast 26S proteasome purification
      procedure, by which we find that a sizeable fraction of Doa4 copurifies with the
      protease. Another yeast deubiquitinating enzyme, Ubp5, which is related in
      sequence to Doa4 but cannot substitute for it even when overproduced, does not
      associate with the proteasome. DOA4-UBP5 chimeras were made by a novel PCR/yeast
      recombination method and used to identify an N-terminal 310-residue domain of
      Doa4 that, when appended to the catalytic domain of Ubp5, conferred Doa4
      function, consistent with Ubp enzymes having a modular architecture. Unlike Ubp5,
      a functional Doa4-Ubp5 chimera associates with the proteasome, suggesting that
      proteasome binding is important for Doa4 function. Together, these data support a
      model in which Doa4 promotes proteolysis through removal of ubiquitin from
      proteolytic intermediates on the proteasome before or after initiation of
      substrate breakdown.

PMID- 10069816
TI  - Short DNA fragments without sequence similarity are initiation sites for
      replication in the chromosome of the yeast Yarrowia lipolytica.
AB  - We have previously shown that both a centromere (CEN) and a replication origin
      are necessary for plasmid maintenance in the yeast Yarrowia lipolytica ().
      Because of this requirement, only a small number of centromere-proximal
      replication origins have been isolated from Yarrowia. We used a CEN-based plasmid
      to obtain noncentromeric origins, and several new fragments, some unique and some
      repetitive sequences, were isolated. Some of them were analyzed by two
      dimensional gel electrophoresis and correspond to actual sites of initiation
      (ORI) on the chromosome. We observed that a 125-bp fragment is sufficient for a
      functional ORI on plasmid, and that chromosomal origins moved to ectopic sites on
      the chromosome continue to act as initiation sites. These Yarrowia origins share
      an 8-bp motif, which is not essential for origin function on plasmids. The
      Yarrowia origins do not display any obvious common structural features, like bent
      DNA or DNA unwinding elements, generally present at or near eukaryotic
      replication origins. Y. lipolytica origins thus share features of those in the
      unicellular Saccharomyces cerevisiae and in multicellular eukaryotes: they are
      discrete and short genetic elements without sequence similarity.

PMID- 10069817
TI  - Gene knockouts reveal separate functions for two cytoplasmic dyneins in
      Tetrahymena thermophila.
AB  - In many organisms, there are multiple isoforms of cytoplasmic dynein heavy
      chains, and division of labor among the isoforms would provide a mechanism to
      regulate dynein function. The targeted disruption of somatic genes in Tetrahymena
      thermophila presents the opportunity to determine the contributions of individual
      dynein isoforms in a single cell that expresses multiple dynein heavy chain
      genes. Substantial portions of two Tetrahymena cytoplasmic dynein heavy chain
      genes were cloned, and their motor domains were sequenced. Tetrahymena DYH1
      encodes the ubiquitous cytoplasmic dynein Dyh1, and DYH2 encodes a second
      cytoplasmic dynein isoform, Dyh2. The disruption of DYH1, but not DYH2, resulted
      in cells with two detectable defects: 1) phagocytic activity was inhibited, and
      2) the cells failed to distribute their chromosomes correctly during micronuclear
      mitosis. In contrast, the disruption of DYH2 resulted in a loss of regulation of
      cell size and cell shape and in the apparent inability of the cells to repair
      their cortical cytoskeletons. We conclude that the two dyneins perform separate
      tasks in Tetrahymena.

PMID- 10069818
TI  - Modulation of cell proliferation and differentiation through substrate-dependent
      changes in fibronectin conformation.
AB  - Integrin-mediated cell adhesion to extracellular matrices provides signals
      essential for cell cycle progression and differentiation. We demonstrate that
      substrate-dependent changes in the conformation of adsorbed fibronectin (Fn)
      modulated integrin binding and controlled switching between proliferation and
      differentiation. Adsorption of Fn onto bacterial polystyrene (B), tissue culture
      polystyrene (T), and collagen (C) resulted in differences in Fn conformation as
      indicated by antibody binding. Using a biochemical method to quantify bound
      integrins in cultured cells, we found that differences in Fn conformation altered
      the quantity of bound alpha5 and beta1 integrin subunits but not alphav or beta3.
      C2C12 myoblasts grown on these Fn-coated substrates proliferated to different
      levels (B > T > C). Immunostaining for muscle-specific myosin revealed minimal
      differentiation on B, significant levels on T, and extensive differentiation on
      C. Differentiation required binding to the RGD cell binding site in Fn and was
      blocked by antibodies specific for this site. Switching between proliferation and
      differentiation was controlled by the levels of alpha5beta1 integrin bound to Fn,
      and differentiation was inhibited by anti-alpha5, but not anti-alphav,
      antibodies, suggesting distinct integrin-mediated signaling pathways. Control of
      cell proliferation and differentiation through conformational changes in
      extracellular matrix proteins represents a versatile mechanism to elicit specific
      cellular responses for biological and biotechnological applications.

PMID- 10069820
TI  - The multisensory guard cell. Stomatal responses to blue light and abscisic acid 

PMID- 10069819
TI  - Visualization of receptor-mediated endocytosis in yeast.
AB  - We studied the ligand-induced endocytosis of the yeast alpha-factor receptor
      Ste2p by immuno-electron microscopy. We observed and quantitated time-dependent
      loss of Ste2p from the plasma membrane of cells exposed to alpha-factor. This
      ligand-induced internalization of Ste2p was blocked in the well-characterized
      endocytosis-deficient mutant sac6Delta. We provide evidence that implicates
      furrow-like invaginations of the plasma membrane as the site of receptor
      internalization. These invaginations are distinct from the finger-like plasma
      membrane invaginations within actin cortical patches. Consistent with this, we
      show that Ste2p is not located within the cortical actin patch before and during
      receptor-mediated endocytosis. In wild-type cells exposed to alpha-factor we also
      observed and quantitated a time-dependent accumulation of Ste2p in intracellular,
      membrane-bound compartments. These compartments have a characteristic electron
      density but variable shape and size and are often located adjacent to the
      vacuole. In immuno-electron microscopy experiments these compartments labeled
      with antibodies directed against the rab5 homologue Ypt51p (Vps21p), the resident
      vacuolar protease carboxypeptidase Y, and the vacuolar H+-ATPase Vph1p. Using a
      new double-labeling technique we have colocalized antibodies against Ste2p and
      carboxypeptidase Y to this compartment, thereby identifying these compartments as
      prevacuolar late endosomes.

PMID- 10069821
TI  - NADH-glutamate synthase in alfalfa root nodules. Genetic regulation and cellular
      expression.
AB  - NADH-dependent glutamate synthase (NADH-GOGAT; EC 1.4.1.14) is a key enzyme in
      primary nitrogen assimilation in alfalfa (Medicago sativa L.) root nodules. Here
      we report that in alfalfa, a single gene, probably with multiple alleles, encodes
      for NADH-GOGAT. In situ hybridizations were performed to assess the location of
      NADH-GOGAT transcript in alfalfa root nodules. In wild-type cv Saranac nodules
      the NADH-GOGAT gene is predominantly expressed in infected cells. Nodules devoid
      of bacteroids (empty) induced by Sinorhizobium meliloti 7154 had no NADH-GOGAT
      transcript detectable by in situ hybridization, suggesting that the presence of
      the bacteroid may be important for NADH-GOGAT expression. The pattern of
      expression of NADH-GOGAT shifted during root nodule development. Until d 9 after
      planting, all infected cells appeared to express NADH-GOGAT. By d 19, a gradient
      of expression from high in the early symbiotic zone to low in the late symbiotic
      zone was observed. In 33-d-old nodules expression was seen in only a few cell
      layers in the early symbiotic zone. This pattern of expression was also observed
      for the nifH transcript but not for leghemoglobin. The promoter of NADH-GOGAT was
      evaluated in transgenic alfalfa plants carrying chimeric beta-glucuronidase
      promoter fusions. The results suggest that there are at least four regulatory
      elements. The region responsible for expression in the infected cell zone
      contains an 88-bp direct repeat.

PMID- 10069822
TI  - NADH-Glutamate synthase in alfalfa root nodules. Immunocytochemical localization 
AB  - In root nodules of alfalfa (Medicago sativa L.), N2 is reduced to NH4+ in the
      bacteroid by the nitrogenase enzyme and then released into the plant cytosol. The
      NH4+ is then assimilated by the combined action of glutamine synthetase (EC
      6.3.1.2) and NADH-dependent Glu synthase (NADH-GOGAT; EC 1.4.1.14) into glutamine
      and Glu. The alfalfa nodule NADH-GOGAT protein has a 101-amino acid presequence,
      but the subcellular location of the protein is unknown. Using immunocytochemical
      localization, we determined first that the NADH-GOGAT protein is found throughout
      the infected cell region of both 19- and 33-d-old nodules. Second, in alfalfa
      root nodules NADH-GOGAT is localized predominantly to the amyloplast of infected
      cells. This finding, together with earlier localization and fractionation
      studies, indicates that in alfalfa the infected cells are the main location for
      the initial assimilation of fixed N2.

PMID- 10069823
TI  - Winter survival of transgenic alfalfa overexpressing superoxide dismutase 
AB  - To test the hypothesis that enhanced tolerance of oxidative stress would improve
      winter survival, two clones of alfalfa (Medicago sativa) were transformed with a
      Mn-superoxide dismutase (Mn-SOD) targeted to the mitochondria or to the
      chloroplast. Although Mn-SOD activity increased in most primary transgenic
      plants, both cytosolic and chloroplastic forms of Cu/Zn-SOD had lower activity in
      the chloroplast SOD transgenic plants than in the nontransgenic plants. In a
      field trial at Elora, Ontario, Canada, the survival and yield of 33 primary
      transgenic and control plants were compared. After one winter most transgenic
      plants had higher survival rates than control plants, with some at 100%.
      Similarly, some independent transgenic plants had twice the herbage yield of the
      control plants. Prescreening the transgenic plants for SOD activity, vigor, or
      freezing tolerance in the greenhouse was not effective in identifying individual
      transgenic plants with improved field performance. Freezing injury to leaf blades
      and fibrous roots, measured by electrolyte leakage from greenhouse-grown
      acclimated plants, indicated that the most tolerant were only 1 degrees C more
      freezing-tolerant than alfalfa clone N4. There were no differences among
      transgenic and control plants for tetrazolium staining of field-grown plants at
      any freezing temperature. Therefore, although many of the transgenic plants had
      higher winter survival rates and herbage yield, there was no apparent difference
      in primary freezing injury, and therefore, the trait is not associated with a
      change in the primary site of freezing injury.

PMID- 10069824
TI  - The involvement of hydrogen peroxide in the differentiation of secondary walls in
      cotton fibers 
AB  - H2O2 is a widespread molecule in many biological systems. It is created
      enzymatically in living cells during various oxidation reactions and by leakage
      of electrons from the electron transport chains. Depending on the concentration
      H2O2 can induce cell protective responses, programmed cell death, or necrosis.
      Here we provide evidence that H2O2 may function as a developmental signal in the
      differentiation of secondary walls in cotton (Gossypium hirsutum) fibers. Three
      lines of evidence support this conclusion: (a) the period of H2O2 generation
      coincided with the onset of secondary wall deposition, (b) inhibition of H2O2
      production or scavenging the available H2O2 from the system prevented the wall
      differentiation process, and (c) exogenous addition of H2O2 prematurely promoted
      secondary wall formation in young fibers. Furthermore, we provide support for the
      concept that H2O2 generation could be mediated by the expression of the small
      GTPase Rac, the accumulation of which was shown previously to be strongly induced
      during the onset of secondary wall differentiation. In support of Rac's role in
      the activation of NADPH oxidase and the generation of reactive oxygen species, we
      transformed soybean (Glycine max) and Arabidopsis cells with mutated Rac genes.
      Transformation with a dominantly activated cotton Rac13 gene resulted in
      constitutively higher levels of H2O2, whereas transformation with the antisense
      and especially with dominant-negative Rac constructs decreased the levels of
      H2O2.

PMID- 10069825
TI  - A single limit dextrinase gene is expressed both in the developing endosperm and
      in germinated grains of barley.
AB  - The single gene encoding limit dextrinase (pullulan 6-glucanohydrolase; EC
      3.2.1.41) in barley (Hordeum vulgare) has 26 introns that range in size from 93
      to 822 base pairs. The mature polypeptide encoded by the gene has 884 amino acid
      residues and a calculated molecular mass of 97,417 D. Limit dextrinase mRNA is
      abundant in gibberellic acid-treated aleurone layers and in germinated grain.
      Gibberellic acid response elements were found in the promoter region of the gene.
      These observations suggest that the enzyme participates in starch hydrolysis
      during endosperm mobilization in germinated grain. The mRNA encoding the enzyme
      is present at lower levels in the developing endosperm of immature grain, a
      location consistent with a role for limit dextrinase in starch synthesis. Enzyme
      activity was also detected in developing grain. The limit dextrinase has a
      presequence typical of transit peptides that target nascent polypeptides to
      amyloplasts, but this would not be expected to direct secretion of the mature
      enzyme from aleurone cells in germinated grain. It remains to be discovered how
      the enzyme is released from the aleurone and whether another enzyme, possibly of
      the isoamylase group, might be equally important for starch hydrolysis in
      germinated grain.

PMID- 10069826
TI  - Characterization of Chlamydomonas reinhardtii zygote-specific cDNAs that encode
      novel proteins containing ankyrin repeats and WW domains.
AB  - Genes that are expressed only in the young zygote are considered to be of great
      importance in the development of an isogamous green alga, Chlamydomonas
      reinhardtii. Clones representing the Zys3 gene were isolated from a cDNA library
      prepared using zygotes at 10 min after fertilization. Sequencing of Zys3 cDNA
      clones resulted in the isolation of two related molecular species. One of them
      encoded a protein that contained two kinds of protein-to-protein interaction
      motifs known as ankyrin repeats and WW domains. The other clone lacked the
      ankyrin repeats but was otherwise identical. These mRNA species began to
      accumulate simultaneously in cells beginning 10 min after fertilization, and
      reached maximum levels at about 4 h, after which time levels decreased markedly.
      Genomic DNA gel-blot analysis indicated that Zys3 was a single-copy gene. The
      Zys3 proteins exhibited parallel expression to the Zys3 mRNAs at first, appearing
      2 h after mating, and reached maximum levels at more than 6 h, but persisted to
      at least 1 d. Immunocytochemical analysis revealed their localization in the
      endoplasmic reticulum, which suggests a role in the morphological changes of the
      endoplasmic reticulum or in the synthesis and transport of proteins to the Golgi
      apparatus or related vesicles.

PMID- 10069827
TI  - Osmotic water permeability of isolated protoplasts. Modifications during
      development 
AB  - A transference chamber was developed to measure the osmotic water permeability
      coefficient (Pos) in protoplasts 40 to 120 MUm in diameter. The protoplast was
      held by a micropipette and submitted to a steep osmotic gradient created in the
      transference chamber. Pos was derived from the changes in protoplast dimensions,
      as measured using a light microscope. Permeabilities were in the range 1 to 1000
      MUm s-1 for the various types of protoplasts tested. The precision for Pos was
      </=40%, and within this limit, no asymmetry in the water fluxes was observed.
      Measurements on protoplasts isolated from 2- to 5-d-old roots revealed a dramatic
      increase in Pos during root development. A shift in Pos from 10 to 500 MUm s-1
      occurred within less than 48 h. This phenomenon was found in maize (Zea mays),
      wheat (Triticum aestivum), and rape (Brassica napus) roots. These results show
      that early developmental processes modify water-transport properties of the
      plasma membrane, and that the transference chamber is adapted to the study of
      water-transport mechanisms in native membranes.

PMID- 10069828
TI  - The Arabidopsis dwarf1 mutant is defective in the conversion of 24
      methylenecholesterol to campesterol in brassinosteroid biosynthesis.
AB  - Since the isolation and characterization of dwarf1-1 (dwf1-1) from a T-DNA
      insertion mutant population, phenotypically similar mutants, including
      deetiolated2 (det2), constitutive photomorphogenesis and dwarfism (cpd),
      brassinosteroid insensitive1 (bri1), and dwf4, have been reported to be defective
      in either the biosynthesis or the perception of brassinosteroids. We present
      further characterization of dwf1-1 and additional dwf1 alleles. Feeding tests
      with brassinosteroid-biosynthetic intermediates revealed that dwf1 can be rescued
      by 22alpha-hydroxycampesterol and downstream intermediates in the brassinosteroid
      pathway. Analysis of the endogenous levels of brassinosteroid intermediates
      showed that 24-methylenecholesterol in dwf1 accumulates to 12 times the level of
      the wild type, whereas the level of campesterol is greatly diminished, indicating
      that the defective step is in C-24 reduction. Furthermore, the deduced amino acid
      sequence of DWF1 shows significant similarity to a flavin adenine dinucleotide
      binding domain conserved in various oxidoreductases, suggesting an enzymatic role
      for DWF1. In support of this, 7 of 10 dwf1 mutations directly affected the flavin
      adenine dinucleotide-binding domain. Our molecular characterization of dwf1
      alleles, together with our biochemical data, suggest that the biosynthetic defect
      in dwf1 results in reduced synthesis of bioactive brassinosteroids, causing
      dwarfism.

PMID- 10069829
TI  - Phytochrome D acts in the shade-avoidance syndrome in Arabidopsis by controlling
      elongation growth and flowering time.
AB  - Shade avoidance in higher plants is regulated by the action of multiple
      phytochrome (phy) species that detect changes in the red/far-red ratio (R/FR) of
      incident light and initiate a redirection of growth and an acceleration of
      flowering. The phyB mutant of Arabidopsis is constitutively elongated and early
      flowering and displays attenuated responses to both reduced R/FR and end-of-day
      far-red light, conditions that induce strong shade-avoidance reactions in wild
      type plants. This indicates that phyB plays an important role in the control of
      shade avoidance. In Arabidopsis phyB and phyD are the products of a recently
      duplicated gene and share approximately 80% identity. We investigated the role
      played by phyD in shade avoidance by analyzing the responses of phyD-deficient
      mutants. Compared with the monogenic phyB mutant, the phyB-phyD double mutant
      flowers early and has a smaller leaf area, phenotypes that are characteristic of
      shade avoidance. Furthermore, compared with the monogenic phyB mutant, the phyB
      phyD double mutant shows a more attenuated response to a reduced R/FR for these
      responses. Compared with the phyA-phyB double mutant, the phyA-phyB-phyD triple
      mutant has elongated petioles and displays an enhanced elongation of internodes
      in response to end-of-day far-red light. These characteristics indicate that phyD
      acts in the shade-avoidance syndrome by controlling flowering time and leaf area
      and that phyC and/or phyE also play a role.

PMID- 10069830
TI  - Chloroplast-avoidance response induced by high-fluence blue light in prothallial
      cells of the fern adiantum capillus-veneris as analyzed by microbeam irradiation 
AB  - Chloroplast movement was induced by partial cell illumination using a high
      fluence blue microbeam in light-grown and dark-adapted prothallial cells of the
      fern Adiantum capillus-veneris. Chloroplasts inside the illuminated area moved
      out (high-fluence response [HFR]), whereas those outside moved toward the
      irradiated area (low-fluence response [LFR]), although they stopped moving when
      they reached the border. These results indicate that both HFR and LFR signals are
      generated by high-fluence blue light of the same area, and that an LFR signal can
      be transferred long-distance from the beam spot, although an HFR signal cannot.
      The lifetime of the HFR signal was calculated from the traces of chloroplast
      movement induced by a brief pulse from a high-fluence blue microbeam to be about
      6 min. This is very short compared with that of the LFR (30-40 min; T. Kagawa, M.
      Wada [1994] J Plant Res 107: 389-398). These data indicate that the signal
      transduction pathways of the HFR and the LFR must be distinct.

PMID- 10069831
TI  - GTPase activity and biochemical characterization of a recombinant cotton fiber
      annexin.
AB  - A cDNA encoding annexin was isolated from a cotton (Gossypium hirsutum) fiber
      cDNA library. The cDNA was expressed in Escherichia coli, and the resultant
      recombinant protein was purified. We then investigated some biochemical
      properties of the recombinant annexin based on the current understanding of plant
      annexins. An "add-back experiment" was performed to study the effect of the
      recombinant annexin on beta-glucan synthase activity, but no effect was found.
      However, it was found that the recombinant annexin could display ATPase/GTPase
      activities. The recombinant annexin showed much higher GTPase than ATPase
      activity. Mg2+ was essential for these activities, whereas a high concentration
      of Ca2+ was inhibitory. A photolabeling assay showed that this annexin could bind
      GTP more specifically than ATP. The GTP-binding site on the annexin was mapped
      into the carboxyl-terminal fourth repeat of annexin from the photolabeling
      experiment using domain-deletion mutants of this annexin. Northern-blot analysis
      showed that the annexin gene was highly expressed in the elongation stages of
      cotton fiber differentiation, suggesting a role of this annexin in cell
      elongation.

PMID- 10069832
TI  - Isolation of ethylene-insensitive soybean mutants that are altered in pathogen
      susceptibility and gene-for-gene disease resistance 
AB  - Plants commonly respond to pathogen infection by increasing ethylene production,
      but it is not clear if this ethylene does more to promote disease susceptibility
      or disease resistance. Ethylene production and/or responsiveness can be altered
      by genetic manipulation. The present study used mutagenesis to identify soybean
      (Glycine max L. Merr.) lines with reduced sensitivity to ethylene. Two new
      genetic loci were identified, Etr1 and Etr2. Mutants were compared with isogenic
      wild-type parents for their response to different soybean pathogens. Plant lines
      with reduced ethylene sensitivity developed similar or less-severe disease
      symptoms in response to virulent Pseudomonas syringae pv glycinea and
      Phytophthora sojae, but some of the mutants developed similar or more-severe
      symptoms in response to Septoria glycines and Rhizoctonia solani. Gene-for-gene
      resistance against P. syringae expressing avrRpt2 remained effective, but Rps1-k
      mediated resistance against P. sojae races 4 and 7 was disrupted in the strong
      ethylene-insensitive etr1-1 mutant. Rps1-k-mediated resistance against P. sojae
      race 1 remained effective, suggesting that the Rps1-k locus may encode more than
      one gene for disease resistance. Overall, our results suggest that reduced
      ethylene sensitivity can be beneficial against some pathogens but deleterious to
      resistance against other pathogens.

PMID- 10069833
TI  - Regulation of soybean nodulation independent of ethylene signaling 
AB  - Leguminous plants regulate the number of Bradyrhizobium- or Rhizobium-infected
      sites that develop into nitrogen-fixing root nodules. Ethylene has been
      implicated in the regulation of nodule formation in some species, but this role
      has remained in question for soybean (Glycine max). The present study used
      soybean mutants with decreased responsiveness to ethylene, soybean mutants with
      defective regulation of nodule number, and Ag+ inhibition of ethylene perception
      to examine the role of ethylene in the regulation of nodule number. Nodule
      numbers on ethylene-insensitive mutants and plants treated with Ag+ were similar
      to those on wild-type plants and untreated plants, respectively. Hypernodulating
      mutants displayed wild-type ethylene sensitivity. Suppression of nodule numbers
      by high nitrate was also similar between ethylene-insensitive plants, wild-type
      plants, and plants treated with Ag+. Ethylene insensitivity of the roots of etr1
      1 mutants was confirmed using assays for sensitivity to 1-aminocyclopropane-1
      carboxylic acid and for ethylene-stimulated root-hair formation. Additional
      phenotypes of etr1-1 roots were also characterized. Ethylene-dependent pathways
      regulate the number of nodules that form on species such as pea and Medicago
      truncatula, but our data indicate that ethylene is less significant in regulating
      the number of nodules that form on soybean.

PMID- 10069834
TI  - A multisubunit acetyl coenzyme A carboxylase from soybean.
AB  - A multisubunit form of acetyl coenzyme A (CoA) carboxylase (ACCase) from soybean
      (Glycine max) was characterized. The enzyme catalyzes the formation of malonyl
      CoA from acetyl CoA, a rate-limiting step in fatty acid biosynthesis. The four
      known components that constitute plastid ACCase are biotin carboxylase (BC),
      biotin carboxyl carrier protein (BCCP), and the alpha- and beta-subunits of
      carboxyltransferase (alpha- and beta-CT). At least three different cDNAs were
      isolated from germinating soybean seeds that encode BC, two that encode BCCP, and
      four that encode alpha-CT. Whereas BC, BCCP, and alpha-CT are products of nuclear
      genes, the DNA that encodes soybean beta-CT is located in chloroplasts.
      Translation products from cDNAs for BC, BCCP, and alpha-CT were imported into
      isolated pea (Pisum sativum) chloroplasts and became integrated into ACCase.
      Edman microsequence analysis of the subunits after import permitted the
      identification of the amino-terminal sequence of the mature protein after removal
      of the transit sequences. Antibodies specific for each of the chloroplast ACCase
      subunits were generated against products from the cDNAs expressed in bacteria.
      The antibodies permitted components of ACCase to be followed during fractionation
      of the chloroplast stroma. Even in the presence of 0.5 M KCl, a complex that
      contained BC plus BCCP emerged from Sephacryl 400 with an apparent molecular mass
      greater than about 800 kD. A second complex, which contained alpha- and beta-CT,
      was also recovered from the column, and it had an apparent molecular mass of
      greater than about 600 kD. By mixing the two complexes together at appropriate
      ratios, ACCase enzymatic activity was restored. Even higher ACCase activities
      were recovered by mixing complexes from pea and soybean. The results demonstrate
      that the active form of ACCase can be reassembled and that it could form a high
      molecular-mass complex.

PMID- 10069835
TI  - A novel alkaline alpha-galactosidase from melon fruit with a substrate preference
      for raffinose 
AB  - The cucurbits translocate the galactosyl-sucrose oligosaccharides raffinose and
      stachyose, therefore, alpha-galactosidase (alpha-D-galactoside galactohydrolase,
      EC 3.2.1.22) is expected to function as the initial enzyme of photoassimilate
      catabolism. However, the previously described alkaline alpha-galactosidase is
      specific for the tetrasaccharide stachyose, leaving raffinose catabolism in these
      tissues as an enigma. In this paper we report the partial purification and
      characterization of three alpha-galactosidases, including a novel alkaline alpha
      galactosidase (form I) from melon (Cucumis melo) fruit tissue. The form I enzyme
      showed preferred activity with raffinose and significant activity with stachyose.
      Other unique characteristics of this enzyme, such as weak product inhibition by
      galactose (in contrast to the other alpha-galactosidases, which show stronger
      product inhibition), also impart physiological significance. Using raffinose and
      stachyose as substrates in the assays, the activities of the three alpha
      galactosidases (alkaline form I, alkaline form II, and the acid form) were
      measured at different stages of fruit development. The form I enzyme activity
      increased during the early stages of ovary development and fruit set, in contrast
      to the other alpha-galactosidase enzymes, both of which declined in activity
      during this period. In the mature, sucrose-accumulating mesocarp, the alkaline
      form I enzyme was the major alpha-galactosidase present. We also observed
      hydrolysis of raffinose at alkaline conditions in enzyme extracts from other
      cucurbit sink tissues, as well as from young Coleus blumei leaves. Our results
      suggest different physiological roles for the alpha-galactosidase forms in the
      developing cucurbit fruit, and show that the newly discovered enzyme plays a
      physiologically significant role in photoassimilate partitioning in cucurbit sink
      tissue.

PMID- 10069837
TI  - Root xylem embolisms and refilling. Relation To water potentials of soil, roots,
      and leaves, and osmotic potentials of root xylem Sap 
AB  - Embolism and refilling of vessels was monitored directly by cryomicroscopy of
      field-grown corn (Zea mays L.) roots. To test the reliability of an earlier study
      showing embolism refilling in roots at negative leaf water potentials, embolisms
      were counted, and root water potentials (Psiroot) and osmotic potentials of
      exuded xylem sap from the same roots were measured by isopiestic psychrometry.
      All vessels were full at dawn (Psiroot -0.1 MPa). Embolisms were first seen in
      late metaxylem vessels at 8 AM. Embolized late metaxylem vessels peaked at 50% at
      10 AM (Psiroot -0.1 MPa), fell to 44% by 12 PM (Psiroot -0.23 MPa), then dropped
      steadily to zero by early evening (Psiroot -0.28 MPa). Transpiration was highest
      (8.5 MUg cm-2 s-1) between 12 and 2 PM when the percentage of vessels embolized
      was falling. Embolized vessels were refilled by liquid moving through their
      lateral walls. Xylem sap was very low in solutes. The mechanism of vessel
      refilling, when Psiroot is negative, requires further investigation. Daily
      embolism and refilling in roots of well-watered plants is a normal occurrence and
      may be a component of an important hydraulic signaling mechanism between roots
      and shoots.

PMID- 10069836
TI  - Antisense expression of the CK2 alpha-subunit gene in Arabidopsis. Effects on
      light-regulated gene expression and plant growth.
AB  - The protein kinase CK2 (formerly casein kinase II) is thought to be involved in
      light-regulated gene expression in plants because of its ability to phosphorylate
      transcription factors that bind to the promoter regions of light-regulated genes
      in vitro. To address this possibility in vivo and to learn more about the
      potential physiological roles of CK2 in plants, we transformed Arabidopsis with
      an antisense construct of the CK2 alpha-subunit gene and investigated both
      morphological and molecular phenotypes. Antisense transformants had a smaller
      adult leaf size and showed increased expression of chs in darkness and of cab and
      rbcS after red-light treatment. The latter molecular phenotype implied that CK2
      might serve as one of several negative and quantitative effectors in light
      regulated gene expression. The possible mechanism of CK2 action and its
      involvement in the phytochrome signal transduction pathway are discussed.

PMID- 10069838
TI  - Study of the 3-hydroxy eicosanoyl-coenzyme A dehydratase and (E)-2,3 enoyl
      coenzyme A reductase involved in acyl-coenzyme A elongation in etiolated leek
      seedlings 
AB  - (R,S)-[1-14C]3-Hydroxy eicosanoyl-coenzyme A (CoA) has been chemically
      synthesized to study the 3-hydroxy acyl-CoA dehydratase involved in the acyl-CoA
      elongase of etiolated leek (Allium porrum L. ) seedling microsomes. 3-Hydroxy
      eicosanoyl-CoA (3-OH C20:0-CoA) dehydration led to the formation of (E)-2,3
      eicosanoyl-CoA, which has been characterized. Our kinetic studies have determined
      the optimal conditions of the dehydration and also resolved the stereospecificity
      requirement of the dehydratase for (R)-3-OH C20:0-CoA. Isotopic dilution
      experiments showed that 3-hydroxy acyl-CoA dehydratase had a marked preference
      for (R)-3-OH C20:0-CoA. Moreover, the very-long-chain synthesis using (R)-3-OH
      C20:0-CoA isomer and [2-14C]malonyl-CoA was higher than that using the (S)
      isomer, whatever the malonyl-CoA and the 3-OH C20:0-CoA concentrations. We have
      also used [1-14C]3-OH C20:0-CoA to investigate the reductant requirement of the
      enoyl-CoA reductase of the acyl-CoA elongase complex. In the presence of NADPH,
      [1-14C]3-OH C20:0-CoA conversion was stimulated. Aside from the product of
      dehydration, i.e. (E)-2,3 eicosanoyl-CoA, we detected eicosanoyl-CoA resulting
      from the reduction of (E)-2,3 eicosanoyl-CoA. When we replaced NADPH with NADH,
      the eicosanoyl-CoA was 8- to 10-fold less abundant. Finally, in the presence of
      malonyl-CoA and NADPH or NADH, [1-14C]3-OH C20:0-CoA led to the synthesis of very
      long-chain fatty acids. This synthesis was measured using [1-14C]3-OH C20:0-CoA
      and malonyl-CoA or (E)-2,3 eicosanoyl-CoA and [2-14C]malonyl-CoA. In both
      conditions and in the presence of NADPH, the acyl-CoA elongation activity was
      about 60 nmol mg-1 h-1, which is the highest ever reported for a plant system.

PMID- 10069839
TI  - Mannose inhibits Arabidopsis germination via a hexokinase-mediated step.
AB  - Low concentrations of the glucose (Glc) analog mannose (Man) inhibit germination
      of Arabidopsis seeds. Man is phosphorylated by hexokinase (HXK), but the absence
      of germination was not due to ATP or phosphate depletion. The addition of
      metabolizable sugars reversed the Man-mediated inhibition of germination.
      Carbohydrate-mediated regulation of gene expression involving a HXK-mediated
      pathway is known to be activated by Glc, Man, and other monosaccharides.
      Therefore, we investigated whether Man blocks germination through this system. By
      testing other Glc analogs, we found that 2-deoxyglucose, which, like Man, is
      phosphorylated by HXK, also blocked germination; no inhibition was observed with
      6-deoxyglucose or 3-O-methylglucose, which are not substrates for HXK. Since
      these latter two sugars are taken up at a rate similar to that of Man, uptake is
      unlikely to be involved in the inhibition of germination. Furthermore, we show
      that mannoheptulose, a specific HXK inhibitor, restores germination of seeds
      grown in the presence of Man. We conclude that HXK is involved in the Man
      mediated repression of germination of Arabidopsis seeds, possibly via energy
      depletion.

PMID- 10069840
TI  - Oxaloacetate transport into plant mitochondria 
AB  - The properties of oxaloacetate (OA) transport into mitochondria from potato
      (Solanum tuberosum) tuber and pea (Pisum sativum) leaves were studied by
      measuring the uptake of 14C-labeled OA into liposomes with incorporated
      mitochondrial membrane proteins preloaded with various dicarboxylates or citrate.
      OA was found to be transported in an obligatory counterexchange with malate, 2
      oxoglutarate, succinate, citrate, or aspartate. Phtalonate inhibited all of these
      countertransports. OA-malate countertransport was inhibited by 4, 4'
      dithiocyanostilbene-2,2'-disulfonate and pyridoxal phosphate, and also by p
      chloromercuribenzene sulfonate and mersalyl, indicating that a lysine and a
      cysteine residue of the translocator protein are involved in the transport. From
      these and other inhibition studies, we concluded that plant mitochondria contain
      an OA translocator that differs from all other known mitochondrial translocators.
      Major functions of this translocator are the export of reducing equivalents from
      the mitochondria via the malate-OA shuttle and the export of citrate via the
      citrate-OA shuttle. In the cytosol, citrate can then be converted either into 2
      oxoglutarate for use as a carbon skeleton for nitrate assimilation or into acetyl
      coenzyme A for use as a precursor for fatty acid elongation or isoprenoid
      biosynthesis.

PMID- 10069841
TI  - A photoperiod-insensitive barley line contains a light-labile phytochrome B 
AB  - Barley (Hordeum vulgare L.) is a long-day plant whose flowering is enhanced when
      the photoperiod is supplemented with far-red light, and this promotion is
      mediated by phytochrome. A chemically mutagenized dwarf cultivar of barley was
      selected for early flowering time (barley maturity daylength response [BMDR]-1)
      and was made isogenic with the cultivar Shabet (BMDR-8) by backcrossing. BMDR-1
      was found to contain higher levels of both phytochrome A and phytochrome B in the
      dark on immunoblots with monoclonal antibodies from oat (Avena sativa L.) that
      are specific to different members of the phytochrome gene family. Phytochrome A
      was light labile in both BMDR-1 and BMDR-8, decreasing to very low levels after 4
      d of growth in the light. Phytochrome B was light stable in BMDR-8, being equal
      in both light and darkness. However, phytochrome B became light labile in BMDR-1
      and this destabilization of phytochrome B appeared to make BMDR-1 insensitive to
      photoperiod. In addition, both the mutant and the wild type lacked any
      significant promotion of flowering in response to a pulse of far-red light given
      at the end of day, and the end-of-day, far-red inhibition of tillering is normal
      in both, suggesting that phytochrome B is not involved with these responses in
      barley.

PMID- 10069842
TI  - Nitrate-ammonium synergism in rice. A subcellular flux analysis 
AB  - Many reports have shown that plant growth and yield is superior on mixtures of
      NO3- and NH4+ compared with provision of either N source alone. Despite its clear
      practical importance, the nature of this N-source synergism at the cellular level
      is poorly understood. In the present study we have used the technique of
      compartmental analysis by efflux and the radiotracer 13N to measure cellular
      turnover kinetics, patterns of flux partitioning, and cytosolic pool sizes of
      both NO3- and NH4+ in seedling roots of rice (Oryza sativa L. cv IR72), supplied
      simultaneously with the two N sources. We show that plasma membrane fluxes for
      NH4+, cytosolic NH4+ accumulation, and NH4+ metabolism are enhanced by the
      presence of NO3-, whereas NO3- fluxes, accumulation, and metabolism are strongly
      repressed by NH4+. However, net N acquisition and N translocation to the shoot
      with dual N-source provision are substantially larger than when NO3- or NH4+ is
      provided alone at identical N concentrations.

PMID- 10069843
TI  - Overexpression of a novel Arabidopsis gene related to putative zinc-transporter
      genes from animals can lead to enhanced zinc resistance and accumulation.
AB  - We describe the isolation of an Arabidopsis gene that is closely related to the
      animal ZnT genes (Zn transporter). The protein encoded by the ZAT (Zn transporter
      of Arabidopsis thaliana) gene has 398 amino acid residues and is predicted to
      have six membrane-spanning domains. To obtain evidence for the postulated
      function of the Arabidopsis gene, transgenic plants with the ZAT coding sequence
      under control of the cauliflower mosaic virus 35S promoter were analyzed. Plants
      obtained with ZAT in the sense orientation exhibited enhanced Zn resistance and
      strongly increased Zn content in the roots under high Zn exposure. Antisense mRNA
      producing plants were viable, with a wild-type level of Zn resistance and
      content, like plants expressing a truncated coding sequence lacking the C
      terminal cytoplasmic domain of the protein. The availability of ZAT can lead to a
      better understanding of the mechanism of Zn homeostasis and resistance in plants.

PMID- 10069844
TI  - Further studies of the role of cyclic beta-glucans in symbiosis. An NdvC mutant
      of Bradyrhizobium japonicum synthesizes cyclodecakis-(1-->3)-beta-glucosyl.
AB  - The cyclic beta-(1-->3),beta-(1-->6)-D-glucan synthesis locus of Bradyrhizobium
      japonicum is composed of at least two genes, ndvB and ndvC. Mutation in either
      gene affects glucan synthesis, as well as the ability of the bacterium to
      establish a successful symbiotic interaction with the legume host soybean
      (Glycine max). B. japonicum strain AB-14 (ndvB::Tn5) does not synthesize beta
      glucans, and strain AB-1 (ndvC::Tn5) synthesizes a cyclic beta-glucan lacking
      beta-(1-->6)-glycosidic bonds. We determined that the structure of the glucan
      synthesized by strain AB-1 is cyclodecakis-(1-->3)-beta-D-glucosyl, a cyclic beta
      (1-->3)-linked decasaccharide in which one of the residues is substituted in the
      6 position with beta-laminaribiose. Cyclodecakis-(1-->3)-beta-D-glucosyl did not
      suppress the fungal beta-glucan-induced plant defense response in soybean
      cotyledons and had much lower affinity for the putative membrane receptor protein
      than cyclic beta-(1-->3),beta-(1-->6)-glucans produced by wild-type B. japonicum.
      This is consistent with the hypothesis presented previously that the wild-type
      cyclic beta-glucans may function as suppressors of a host defense response.

PMID- 10069845
TI  - Embryo-specific gene expression in microspore-derived embryos of brassica napus.
      An interaction between abscisic acid and jasmonic acid1,2 
AB  - The induction of napin and oleosin gene expression in Brassica napus microspore
      derived embryos (MDEs) was studied to assess the possible interaction between
      abscisic acid (ABA) and jasmonic acid (JA). Napin and oleosin transcripts were
      detected sooner following treatment with ABA than JA. Treatment of MDEs with ABA
      plus JA gave an additive accumulation of both napin and oleosin mRNA, the
      absolute amount being dependent on the concentration of each hormone. Endogenous
      ABA levels were reduced by 10-fold after treatment with JA, negating the
      possibility that the observed additive interaction was due to JA-induced ABA
      biosynthesis. Also, JA did not significantly increase the uptake of [3H-ABA] from
      the medium into MDEs. This suggests that the additive interaction was not due to
      an enhanced carrier-mediated ABA uptake by JA. Finally, when JA was added to MDEs
      that had been treated with the ABA biosynthesis inhibitor fluridone, napin mRNA
      did not increase. Based on these results with the MDE system, it is possible that
      embryos of B. napus use endogenous JA to modulate ABA effects on expression of
      both napin and oleosin. In addition, JA could play a causal role in the reduction
      of ABA that occurs during late stages of seed development.

PMID- 10069846
TI  - Impacts of aluminum on the cytoskeleton of the maize root apex. short-term
      effects on the distal part of the transition zone 
AB  - Using monoclonal tubulin and actin antibodies, Al-mediated alterations to
      microtubules (MTs) and actin microfilaments (MFs) were shown to be most prominent
      in cells of the distal part of the transition zone (DTZ) of an Al-sensitive maize
      (Zea mays L.) cultivar. An early response to Al (1 h, 90 MUM) was the depletion
      of MTs in cells of the DTZ, specifically in the outermost cortical cell file.
      However, no prominent changes to the MT cytoskeleton were found in elongating
      cells treated with Al for 1 h in spite of severe inhibition of root elongation.
      Al-induced early alterations to actin MFs were less dramatic and consisted of
      increased actin fluorescence of partially disintegrated MF arrays in cells of the
      DTZ. These tissue- and development-specific alterations to the cytoskeleton were
      preceded by and/or coincided with Al-induced depolarization of the plasma
      membrane and with callose formation, particularly in the outer cortex cells of
      the DTZ. Longer Al supplies (>6 h) led to progressive enhancements of lesions to
      the MT cytoskeleton in the epidermis and two to three outer cortex cell files.
      Our data show that the cytoskeleton in the cells of the DTZ is especially
      sensitive to Al, consistent with the recently proposed specific Al sensitivity of
      this unique, apical maize root zone.

PMID- 10069847
TI  - The mechanism of rhythmic ethylene production in sorghum. The role of phytochrome
      B and simulated shading.
AB  - Mutant sorghum (Sorghum bicolor [L.] Moench) deficient in functional phytochrome
      B exhibits reduced photoperiodic sensitivity and constitutively expresses a shade
      avoidance phenotype. Under relatively bright, high red:far-red light, ethylene
      production by seedlings of wild-type and phytochrome B-mutant cultivars
      progresses through cycles in a circadian rhythm; however, the phytochrome B
      mutant produces ethylene peaks with approximately 10 times the amplitude of the
      wild type. Time-course northern blots show that the mutant's abundance of the 1
      aminocyclopropane-1-carboxylic acid (ACC) oxidase mRNA SbACO2 is cyclic and is
      commensurate with ethylene production, and that ACC oxidase activity follows the
      same pattern. Both SbACO2 abundance and ACC oxidase activity in the wild-type
      plant are very low under this regimen. ACC levels in the two cultivars did not
      demonstrate fluctuations coincident with the ethylene produced. Simulated shading
      caused the wild-type plant to mimic the phenotype of the mutant and to produce
      high amplitude rhythms of ethylene evolution. The circadian feature of the
      ethylene cycle is conditionally present in the mutant and absent in the wild-type
      plant under simulated shading. SbACO2 abundance in both cultivars demonstrates a
      high-amplitude diurnal cycle under these conditions; however, ACC oxidase
      activity, although elevated, does not exhibit a clear rhythm correlated with
      ethylene production. ACC levels in both cultivars show fluctuations corresponding
      to the ethylene rhythm previously observed. It appears that at least two separate
      mechanisms may be involved in generating high-amplitude ethylene rhythms in
      sorghum, one in response to the loss of phytochrome B function and another in
      response to shading.

PMID- 10069848
TI  - Antioxidative defense system, pigment composition, and photosynthetic efficiency
      in two wheat cultivars subjected to drought 
AB  - We analyzed antioxidative defenses, photosynthesis, and pigments (especially
      xanthophyll-cycle components) in two wheat (Triticum durum Desf.) cultivars,
      Adamello and Ofanto, during dehydration and rehydration to determine the
      difference in their sensitivities to drought and to elucidate the role of
      different protective mechanisms against oxidative stress. Drought caused a more
      pronounced inhibition in growth and photosynthetic rates in the more sensitive cv
      Adamello compared with the relatively tolerant cv Ofanto. During dehydration the
      glutathione content decreased in both wheat cultivars, but only cv Adamello
      showed a significant increase in glutathione reductase and hydrogen peroxide
      glutathione peroxidase activities. The activation states of two sulfhydryl
      containing chloroplast enzymes, NADP+-dependent glyceraldehyde-3-phosphate
      dehydrogenase and fructose-1,6-bisphosphatase, were maintained at control levels
      during dehydration and rehydration in both cultivars. This indicates that the
      defense systems involved are efficient in the protection of sulfhydryl groups
      against oxidation. Drought did not cause significant effects on lipid
      peroxidation. Upon dehydration, a decline in chlorophyll a, lutein, neoxanthin,
      and beta-carotene contents, and an increase in the pool of de-epoxidized
      xanthophyll-cycle components (i.e. zeaxanthin and antheraxanthin), were evident
      only in cv Adamello. Accordingly, after exposure to drought, cv Adamello showed a
      larger reduction in the actual photosystem II photochemical efficiency and a
      higher increase in nonradiative energy dissipation than cv Ofanto. Although
      differences in zeaxanthin content were not sufficient to explain the difference
      in drought tolerance between the two cultivars, zeaxanthin formation may be
      relevant in avoiding irreversible damage to photosystem II in the more sensitive
      cultivar.

PMID- 10069849
TI  - Restrictions to carbon dioxide conductance and photosynthesis in spinach leaves
      recovering from salt stress 
AB  - Salt accumulation in spinach (Spinacia oleracea L.) leaves first inhibits
      photosynthesis by decreasing stomatal and mesophyll conductances to CO2 diffusion
      and then impairs ribulose-1, 5-bisphosphate carboxylase/oxygenase (S. Delfine, A.
      Alvino, M. Zacchini, F. Loreto [1998] Aust J Plant Physiol 25: 395-402). We
      measured gas exchange and fluorescence in spinach recovering from salt
      accumulation. When a 21-d salt accumulation was reversed by 2 weeks of salt-free
      irrigation (rewatering), stomatal and mesophyll conductances and photosynthesis
      partially recovered. For the first time, to our knowledge, it is shown that a
      reduction of mesophyll conductance can be reversed and that this may influence
      photosynthesis. Photosynthesis and conductances did not recover when salt
      drainage was restricted and Na content in the leaves was greater than 3% of the
      dry matter. Incomplete recovery of photosynthesis in rewatered and control leaves
      may be attributed to an age-related reduction of conductances. Biochemical
      properties were not affected by the 21-d salt accumulation. However, ribulose-1,
      5-bisphosphate carboxylase/oxygenase activity and content were reduced by a 36-
      to 50-d salt accumulation. Photochemical efficiency was reduced only in 50-d salt
      stressed leaves because of a decrease in the fraction of open photosystem II
      centers. A reduction in chlorophyll content and an increase in the chlorophyll
      a/b ratio were observed in 43- and 50-d salt-stressed leaves. Low chlorophyll
      affects light absorptance but is unlikely to change light partitioning between
      photosystems.

PMID- 10069850
TI  - Nicotianamine chelates both FeIII and FeII. Implications for metal transport in
      plants 
AB  - Nicotianamine (NA) occurs in all plants and chelates metal cations, including
      FeII, but reportedly not FeIII. However, a comparison of the FeII and ZnII
      affinity constants of NA and various FeIII-chelating aminocarboxylates suggested
      that NA should chelate FeIII. High-voltage electrophoresis of the FeNA complex
      formed in the presence of FeIII showed that the complex had a net charge of 0,
      consistent with the hexadentate chelation of FeIII. Measurement of the affinity
      constant for FeIII yielded a value of 10(20.6), which is greater than that for
      the association of NA with FeII (10(12.8)). However, capillary electrophoresis
      showed that in the presence of FeII and FeIII, NA preferentially chelates FeII,
      indicating that the FeIINA complex is kinetically stable under aerobic
      conditions. Furthermore, Fe complexes of NA are relatively poor Fenton reagents,
      as measured by their ability to mediate H2O2-dependent oxidation of deoxyribose.
      This suggests that NA will have an important role in scavenging Fe and protecting
      the cell from oxidative damage. The pH dependence of metal ion chelation by NA
      and a typical phytosiderophore, 2'-deoxymugineic acid, indicated that although
      both have the ability to chelate Fe, when both are present, 2'-deoxymugineic acid
      dominates the chelation process at acidic pH values, whereas NA dominates at
      alkaline pH values. The consequences for the role of NA in the long-distance
      transport of metals in the xylem and phloem are discussed.

PMID- 10069851
TI  - Light-induced changes in hydrogen, calcium, potassium, and chloride ion fluxes
      and concentrations from the mesophyll and epidermal tissues of bean leaves.
      Understanding the ionic basis of light-induced bioelectrogenesis 
AB  - Noninvasive, ion-selective vibrating microelectrodes were used to measure the
      kinetics of H+, Ca2+, K+, and Cl- fluxes and the changes in their concentrations
      caused by illumination near the mesophyll and attached epidermis of bean (Vicia
      faba L.). These flux measurements were related to light-induced changes in the
      plasma membrane potential. The influx of Ca2+ was the main depolarizing agent in
      electrical responses to light in the mesophyll. Changes in the net fluxes of H+,
      K+, and Cl- occurred only after a significant delay of about 2 min, whereas light
      stimulated influx of Ca2+ began within the time resolution of our measurements (5
      s). In the absence of H+ flux, light caused an initial quick rise of external pH
      near the mesophyll and epidermal tissues. In the mesophyll this fast
      alkalinization was followed by slower, oscillatory pH changes (5-15 min); in the
      epidermis the external pH increased steadily and reached a plateau 3 min later.
      We explain the initial alkalinization of the medium as a result of CO2 uptake by
      photosynthesizing tissue, whereas activation of the plasma membrane H+ pump
      occurred 1.5 to 2 min later. The epidermal layer seems to be a substantial
      barrier for ion fluxes but not for CO2 diffusion into the leaf.

PMID- 10069852
TI  - Decrease in phosphoribulokinase activity by antisense RNA in transgenic tobacco.
      Relationship between photosynthesis, growth, and allocation at different nitrogen
      levels 
AB  - To study the direct effects of photosynthesis on allocation of biomass by
      altering photosynthesis without altering leaf N or nitrate content,
      phosphoribulokinase (PRK) activity was decreased in transgenic tobacco (Nicotiana
      tabacum L.) with an inverted tobacco PRK cDNA and plants were grown at different
      N levels (0.4 and 5 mM NH4NO3). The activation state of PRK increased as the
      amount of enzyme was decreased genetically at both levels of N. At high N a 94%
      decrease in PRK activity had only a small effect (20%) on photosynthesis and
      growth. At low N a 94% decrease in PRK activity had a greater effect on leaf
      photosynthesis (decreased by up to 50%) and whole-plant photosynthesis (decreased
      by up to 35%) than at high N. These plants were up to 35% smaller than plants
      with higher PRK activities because they had less structural dry matter and less
      starch, which was decreased by 3- to 4-fold, but still accumulated to 24% to 31%
      of dry weight; young leaves contained more starch than older leaves in older
      plants. Leaves had a higher ion and water content, and specific leaf area was
      higher, but allocation between shoot and root was unaltered. In conclusion, low N
      in addition to a 94% decrease in PRK by antisense reduces the activity of PRK
      sufficient to diminish photosynthesis, which limits biomass production under
      conditions normally considered sink limited.

PMID- 10069853
TI  - Glycerol is a suberin monomer. New experimental evidence for an old hypothesis 
AB  - The monomer composition of the esterified part of suberin can be determined using
      gas chromatography-mass spectroscopy technology and is accordingly believed to be
      well known. However, evidence was presented recently indicating that the suberin
      of green cotton (Gossypium hirsutum cv Green Lint) fibers contains substantial
      amounts of esterified glycerol. This observation is confirmed in the present
      report by a sodium dodecyl sulfate extraction of membrane lipids and by a
      developmental study, demonstrating the correlated accumulation of glycerol and
      established suberin monomers. Corresponding amounts of glycerol also occur in the
      suberin of the periderm of cotton stems and potato (Solanum tuberosum) tubers. A
      periderm preparation of wound-healing potato tuber storage parenchyma was further
      purified by different treatments. As the purification proceeded, the
      concentration of glycerol increased at about the same rate as that of alpha,omega
      alkanedioic acids, the most diagnostic suberin monomers. Therefore, it is
      proposed that glycerol is a monomer of suberins in general and can cross-link
      aliphatic and aromatic suberin domains, corresponding to the electron-translucent
      and electron-opaque suberin lamellae, respectively. This proposal is consistent
      with the reported dimensions of the electron-translucent suberin lamellae.

PMID- 10069854
TI  - Behavior of pythium Torulosum zoospores during their interaction with tobacco
      roots and Bacillus cereus.
AB  - Bacillus cereus UW85 suppresses seedling damping-off diseases caused by Oomycetes
      and produces antibiotics that inhibit development of Oomycetes in culture. The
      goal of this study was to determine how UW85 and its antibiotics affected the
      behavior of an Oomycete, Pythium torulosum, in its interaction with plant roots.
      We studied tobacco seedlings inoculated with zoospores of P. torulosum and UW85
      culture, culture filtrate, washed cells, antibiotics (zwittermicin A or
      kanosamine), purified from cultures of UW85, and UW030, a mutant of UW85 that
      does not suppress disease and does not produce the antibiotics. Microscopic
      observation revealed that all of the treatments inhibited zoospore activity
      around roots and encystment on roots. Treatment with UW85 culture, culture
      filtrate, zwittermicin A, or kanosamine delayed cyst germination and the
      elongation rate of germ tubes, whereas treatment with UW030 or washed UW85 cells
      did not. In an in vitro seedling bioassay of disease suppression, the
      antibiotics, zwittermicin A and kanosamine, suppressed disease singly or
      together, although UW85 culture suppressed disease more effectively than did the
      antibiotics. The results show that B. cereus cultures affect zoospore behavior in
      the presence of roots, and B. cereus-produced antibiotics, zwittermicin A and
      kanosamine, contribute to disease suppression and inhibition of germ tube
      elongation in the presence of the plant root.

PMID- 10069855
TI  - Chemotaxis of Rhizobium sp.S2 towards Cajanus cajan root exudate and its major
      components.
AB  - The chemotactic response of Rhizobium sp. S2, a slow-growing Cajanus cajan
      isolate, towards its host root exudate was examined. Two classes of mutants, one
      nonchemotactic towards nutrients (amino acids and sugars) and signal compounds
      like flavonoids and the other, nonchemotactic towards amino acids and sugars but
      positive towards naringenin, the flavonoid present in Cajanus cajan root exudate,
      were obtained. The plasmid-cured derivative of the parent showed positive
      response towards amino acids and sugars but was nonchemotactic towards
      naringenin. A possible presence of dual chemotaxis pathways, one towards
      nutrients and the other for sensing signal compounds, was thus demonstrated. The
      possible involvement of naringenin as a chemoattractant in the preliminary stages
      of this Rhizobium-legume interaction was also established.

PMID- 10069856
TI  - Isolation and characterization of Synechococcus PCC7942 promoters: tRNApro gene
      functions as a promoter.
AB  - Promoter-active fragments of Synechococcus PCC7942 were isolated by
      transcriptional gene fusion to the promoterless beta-glucuronidase (GUS) gene of
      E. coli, which was used as a reporter gene. Several of the isolated promoter
      active fragments expressed GUS activity in Synechococcus comparable to that of
      the lambdaPR promoter. Only 10% of the isolated promoter-active fragments also
      functioned in E. coli. The transcription initiation sites of the two promoter
      active fragments, D13 and E3, were identified. The major transcription initiation
      sites of D13 and E3 in Synechococcus were located within the nucleotides TTTG and
      TTG respectively, which were identical to those corresponding to E. coli. The
      inferred -10 and -35 regions of D13 were TAAACT and TTGTAG respectively, which
      conformed to the E. coli sigma70 promoter. Immediately upstream of the E3
      transcription initiation sites was the tRNApro (GGG) gene, which contained two
      regions exhibiting strong homology to the major promoter elements in eukaryotic
      tRNA genes, but did not contain the E. coli promoter element. Thus, the tRNApro
      gene can act as a promoter.

PMID- 10069857
TI  - Fingerprinting of mixed bacterial strains and BIOLOG gram-negative (GN) substrate
      communities by enterobacterial repetitive intergenic consensus sequence-PCR (ERIC
      PCR).
AB  - PCR-based genomic fingerprinting by use of enterobacterial repetitive intergenic
      consensus primers (ERIC-PCR) was evaluated for its use in fingerprinting DNA of
      mixed Gram-negative bacterial strains and BIOLOG Gram-negative (GN) microplate
      substrate communities. ERIC-PCR fingerprints of six different pure bacterial
      strains and a combined mixture of the strains were compared with fingerprints
      obtained by two more established methods: amplified ribosomal DNA restriction
      analysis (ARDRA) and random amplified polymorphic DNA analysis (RAPD-PCR). The
      ERIC-PCR fingerprint of the mixed strains was highly reproducible and was more
      species-specific and representative of the individual strain fingerprints than
      the ARDRA and RAPD-PCR fingerprints, respectively. ERIC-PCR fingerprinting of
      model and rhizosphere BIOLOG GN substrate communities also provided clearly
      distinguishable fingerprints. Results of this study suggest that ERIC-PCR
      represents a rapid and highly discriminating method for fingerprinting DNA of
      mixed Gram-negative bacterial strains and BIOLOG GN substrate communities.

PMID- 10069858
TI  - Characterization of the mbl determinant and cloning of the spoIIID gene from
      Bacillus cereus ATCC 10987.
AB  - To examine the transcriptional start site of the putative Bacillus cereus mbl
      gene, we have cloned and sequenced the upstream region of the previously reported
      B. cereus mbl determinant, which showed sequence similarity to the mreB
      morphogene from Escherichia coli. Primer extension analysis revealed the
      transcriptional start site of mbl to 259 bp upstream of the putative
      translational start site and showed that the mbl gene was expressed at 3, 6, and
      10 h of growth after inoculation. Antibodies against B. cereus Mbl showed that
      even though mbl mRNA was present in amounts detectable with Northern blot
      analysis exclusively in the early logarithmic growth phase, the amount of protein
      was constant during the cell cycle. Immunogold labeling cryo-transmission
      electron microscopy indicates that B. cereus Mbl is a cytoplasmic protein. The
      upstream sequence of mbl revealed two open reading frames, spoIIID and orf1. The
      amino acid sequence of B. cereus SpoIIID is identical to the SpoIIID sequence
      from Bacillus thuringiensis. Primer extension showed that mbl is not
      cotranscribed with spoIIID.

PMID- 10069859
TI  - The occurrence of 4-amino-4-deoxy-arabinose in LPS of supersusceptible strain
      Pseudomonas aeruginosa Z61: noncorrelation with polymyxin resistance.
AB  - Lipopolysaccharides (LPS) extracted from the supersusceptible strain Pseudomonas
      aeruginosa Z61 were compared with LPS from other strains with varying
      antimicrobial susceptibilities. The presence of 4-amino-4-deoxy-arabinose (4
      AraN) in P. aeruginosa Z61 LPS was confirmed by gas-liquid chromatography/mass
      spectrometry (GLC-MS) and quantitated by high-performance liquid chromatography
      (HPLC). Z61 LPS (compared with wild-type strain PAO1) has reduced amounts of
      rhamnose and higher concentrations of hydroxy fatty acids, 4-AraN, and
      phosphates. 31P Nuclear magnetic resonance revealed that Z61 LPS phosphates are
      configured in monophosphates, phosphodiesters, pyrophosphomonoesters, and
      glycosidic pyrophosphodiester groups. The presence of 4-AraN in P. aeruginosa LPS
      did not correlate with antimicrobial resistance.

PMID- 10069860
TI  - A nonhemolytic phospholipase C from Burkholderia cepacia.
AB  - Burkholderia cepacia is an opportunistic pathogen that causes serious pulmonary
      infections in cystic fibrosis patients. Although several potential virulence
      factors-a protease, lipase, and two phospholipases C (one hemolytic and one
      nonhemolytic)-have been identified, only two, the protease and the lipase, have
      been described in detail. The goal of this study was to purify and characterize a
      nonhemolytic phospholipase C secreted by B. cepacia strain Pc224c. The enzyme was
      concentrated from culture supernatants and purified by polyacrylamide gel
      electrophoresis. The 54-kDa protein was stable in the presence of sodium dodecyl
      sulfate (up to 10%) and at 4 degrees, 22 degrees, and 37 degrees C; it was,
      however, inactivated at 100 degrees C. The enzyme bound to glass, chromatography
      matrices, and polyvinylidene difluoride and cellulose membranes, suggesting that
      it is hydrophobic. In a genetic approach, primers based on conserved sequences of
      a B. cepacia Pc69 hemolytic phospholipase C and both the Pseudomonas aeruginosa
      hemolytic and nonhemolytic proteins were designed to identify the Pc224c
      nonhemolytic phospholipase C gene. One polymerase chain reaction product was
      identified; it was sequenced and the sequence compared with sequences in the
      BLAST database. The best match was the Pseudomonas aeruginosa hemolytic
      phospholipase C. Ten additional B. cepacia strains were screened for the gene by
      Southern hybridization; five had the 4-kb band, suggesting that these strains
      have a similar form of the PLC gene. Nine of the ten strains reacted with the
      probe, suggesting that similar sequences were present, but in another form.

PMID- 10069861
TI  - The clinically isolated FIZ15 bacteriophage causes lysogenic conversion in
      Pseudomonas aeruginosa PAO1.
AB  - FIZ15 bacteriophage, from a human clinical isolate of Pseudomonas aeruginosa,
      causes lysogenic conversion in the P. aeruginosa strain PAO1. The prophage
      conferred phenotypes are: (1) increased resistance to phagocytosis by mouse
      peritoneal macrophages; (2) increased resistance to killing by normal human
      serum, and (3) increased adhesion to human buccal epithelial cells. These
      phenotypes are related to the prophage-induced change at the level of its own
      bacterial receptor, which appears to be the O-antigen.

PMID- 10069862
TI  - Apoptotic effect of outer-membrane proteins from Campylobacter jejuni on chicken
      lymphocytes.
AB  - Campylobacter jejuni is a significant cause of food-borne diseases in humans. The
      bacterium is considered a commensal organism in chickens, and it can heavily
      colonize chickens without causing inflammation. Poultry may be the major
      reservoir for the human infection in developed countries. Here we show that an
      outer-membrane protein extract prepared from the bacteria caused apoptosis of
      chicken lymphocytes detected in vitro with the terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling assay that preferentially labels
      individual apoptotic cells. Blood- and spleen-lymphocytes from different-aged
      chickens displayed a significantly greater percentage of apoptotic cells after
      culture with the outer-membrane proteins from C. jejuni than controls treated
      with phosphate-buffered saline, chicken ovalbumin, or outer-membrane proteins
      prepared from E. coli strain BL21. The C. jejuni extract also produced apoptosis
      of chicken lymphoblastoid tumor cell lines. Apoptosis was blocked by pretreating
      the extract with proteinase K or antiserum against outer-membrane proteins. The
      results suggest that C. jejuni may be capable of achieving immune avoidance in
      chickens by causing apoptosis of lymphocytes.

PMID- 10069863
TI  - Conversion of unsaturated fatty acids by bacteria isolated from compost.
AB  - A compost mixture amended with soybean oil was enriched in microorganisms that
      transformed unsaturated fatty acids (UFAs). When oleic acid or 10-ketostearic
      acid was the selective fatty acid, Sphingobacterium thalpophilum (NRRL B-23206,
      NRRL B-23208, NRRL B-23209, NRRL B-23210, NRRL B-23211, NRRL B-23212),
      Acinetobacter spp. (NRRL B-23207, NRRL B-23213), and Enterobacter cloacae (NRRL B
      23264, NRRL B-23265, NRRL B-23266) represented isolates that produced either
      hydroxystearic acid, ketostearic acid, or incomplete decarboxylations. When
      ricinoleic (12-hydroxy-9-octadecenoic) acid was the selective UFA, Enterobacter
      cloacae (NRRL B-23257, NRRL B-23267) and Escherichia sp. (NRRL B-23259) produced
      12-C and 14-C homologous compounds, and Pseudomonas aeruginosa (NRRL B-23256,
      NRRL B-23260) converted ricinoleate to a trihydroxyoctadecenoate product. Also,
      various Enterobacter, Pseudomonas, and Serratia spp. appeared to decarboxylate
      linoleate substrate incompletely. These saprophytic, compost bacteria were
      aerobic or facultative anaerobic Gram-negative and decomposed UFAs through
      decarboxylation, hydroxylation, and hydroperoxidation mechanisms.

PMID- 10069865
TI  - Maturation of immune responses at the beginning of asthma.
AB  - The prevalence of childhood asthma appears to be increasing worldwide. A critical
      element in the development of childhood asthma is maturation of the child's
      immune system. Most asthmatic children have a history of recurrent lower
      respiratory tract illnesses associated with airway obstruction during the first
      year of life. Most infants and young children who will go on to have persistent
      wheezing and asthma show high IgE production and eosinophilic immune responses at
      the time of their first viral lower respiratory tract illness. Understanding the
      genetic and environmental factors that regulate the maturation of the immune
      response during early life will greatly enhance the development of strategies for
      the primary and secondary prevention of asthma.

PMID- 10069866
TI  - Immunologic tolerance for immune system-mediated diseases.
AB  - Induction of long-term, antigen-specific immunologic unresponsiveness holds great
      promise for the treatment of many immune system-mediated diseases, including
      asthma, allergies, autoimmune diseases, and transplant rejection. Unlike current
      immunosuppressive treatments, immunologic tolerance therapies would affect only
      the undesired immune responses, leaving protective immunity intact. A variety of
      approaches to immunologic tolerance induction are being taken, reflecting the
      molecular and cellular complexity of immune system activation and regulation. The
      presentations summarized in this report represent promising strategies, some of
      which are being evaluated in advanced animal models and human clinical trials.
      Approaches presented include the following: interference with costimulatory
      signals in T-cell induction, T-cell receptor antagonism by altered peptides,
      exploitation of antigen-induced apoptosis to eliminate undesired T cells,
      opposition of inflammation by the induction of regulatory cytokines, induction of
      transplant tolerance by mixed chimerism, and deviation from deleterious allergic
      antibody responses by use of immunostimulatory DNA sequences. These multifaceted
      approaches are strongly supported by knowledge of basic immune mechanisms, which
      should facilitate the rational development of these therapies for controlling
      immune-mediated diseases.

PMID- 10069867
TI  - Focusing on childhood asthma: the childhood asthma management program (CAMP)

PMID- 10069868
TI  - Leukotriene modifiers: new drugs, old and new reactions.

PMID- 10069870
TI  - Alterations of T-lymphocyte subsets, soluble IL-2 receptor, and IgE in peripheral
      blood of children with acute asthma attacks.
AB  - BACKGROUND: T-cell activation and alteration of cytokines are involved in the
      pathogenesis of atopic asthma. However, the profile of circulating T-lymphocyte
      subsets, related cytokines, and plasma IgE during acute asthma attacks is still
      unclear. OBJECTIVE: In an attempt to illustrate the dynamics of these parameters
      in asthma attacks, we investigated the changes of T-cell subsets, lymphocyte
      activation, soluble IL-2R, and IgE in peripheral blood in children during and
      after acute asthma attacks. METHODS: This study was carried out in a cohort of
      Chinese children (n = 59) with acute asthma attacks. Immunoassays were performed
      when the patients had acute attacks before treatment, and the patients were
      reexamined in the 4 weeks after the resolution of acute attacks with therapy.
      Paired t tests were used for the statistical analysis of these patients to
      compare the data obtained during and after the acute attacks. Twenty healthy, age
      matched subjects were used as normal control subjects. Nine children with long
      term stable asthma were used as control subjects with stable asthma. RESULTS:
      CD3+, CD4+, CD8+, and IL-2R+ (CD25+) cells; plasma soluble IL-2 receptor; and IgE
      were significantly higher in patients with acute attacks than in control
      subjects. (P <.05, P <.05, P <.001, P <.05, P <.0001, and P <.0001,
      respectively). Immunoelectron microscopy exhibited an increased expression of IL
      2R on lymphocytes in acute attacks as compared to control subjects. The
      abnormalities returned to normal, with the exception of IgE, when clinical
      remission was achieved after treatment. Correlation analyses revealed a positive
      relationship between plasma IgE and soluble IL-2R in asthma attacks (r = 0.83, P
      =.0001). Plasma IgE and soluble IL-2R of those who were in remission positively
      correlated with their production in acute attacks (r = 0.58, P =.001 and r =
      0.71, P =.0001, respectively). CONCLUSION: This study suggests that (1) the
      percentage of CD4+, CD8+, or IL-2R+ lymphocytes in peripheral blood was
      significantly elevated during acute attacks and returned to normal ranges after
      complete remission was achieved; (2) plasma soluble IL-2R is a sensitive marker
      for asthma activity; and (3) atopic asthmatic children seem to have a hereditary
      predisposition of having higher levels of soluble IL-2R in asthma attacks,
      coinherited with the trait of IgE.

PMID- 10069869
TI  - Relationships between duration of asthma and asthma severity among children in
      the Childhood Asthma Management Program (CAMP)
AB  - BACKGROUND: Many factors, including heredity, atopic status, and environment,
      have been implicated in the determination of asthma severity. Relatively little
      is known about the degree to which asthma duration influences asthma severity.
      OBJECTIVE: The Childhood Asthma Management Program (CAMP), consisting of 1041
      children (age 8. 9 +/- 2.1 years at enrollment) with mild-to-moderate asthma,
      offers an opportunity to examine the relationship between asthma duration and
      asthma severity. METHODS: By using the extensive CAMP baseline cross-sectional
      data on asthma duration, spirometry, bronchial responsiveness, symptomatology,
      and markers of atopy, univariate and multivariate regression models were used to
      evaluate whether asthma duration is associated with asthma severity. RESULTS:
      Duration of asthma in the study cohort from time of diagnosis until randomization
      into CAMP ranged from 0.3 to 12.1 years (mean, 5.0; SD, 2.7; median, 4.8). Asthma
      duration is associated in univariate analyses both with lower levels of several
      lung functions (P <.001), including methacholine bronchial reactivity (natural
      log [ln] FEV1 PC20, mg/mL; r = -0.112), prebronchodilator and postbronchodilator
      percent predicted FEV1 (r = -0.176 and r = -0.130, respectively), and
      prebronchodilator and postbronchodilator FEV1 /forced vital capacity (FVC) (%) (r
      = -0.237 and r = -0.211, respectively), as well as higher levels of symptoms
      (symptom score: r = 0.147, P <. 001) and borderline greater use of albuterol for
      symptoms (r = 0.058, P =.064) during a 28-day screening period before
      randomization. Simple linear regression detected the following differences in
      lung functions per year of asthma duration: ln FEV1 PC20, -0.050 mg/mL/y;
      prebronchodilator FEV1, -0.907 percent predicted/y; and prebronchodilator FEV1
      /FVC, -0.729 percent predicted/y. After controlling for potential explanatory
      variables (atopy, inflammatory markers, household Der p 1 levels, anti
      inflammatory medication use, and clinical center), regression models revealed
      that the duration of asthma remained significantly and independently associated
      with ln FEV1 PC20 (P =.004), prebronchodilator percent predicted FEV1 (P =.043),
      and prebronchodilator and postbronchodilator FEV1 /FVC (%) (P <.001), as well as
      being positively associated with mean daily symptom score (P <.001) and albuterol
      use for symptoms (P =.003) during a 28-day screening period. Duration was also
      found to be significantly associated with physician/nurse assessment of asthma
      severity and other historical measures of medication use. CONCLUSIONS: These data
      demonstrate that asthma duration is associated with lower lung function, greater
      methacholine responsiveness, more asthma symptomatology, and greater use of as
      needed albuterol, which are all measures of asthma severity. As such, early
      diagnosis and intervention may be necessary to ameliorate these adverse effects
      of persistent asthma.

PMID- 10069871
TI  - Sinus mucosal IL-8 gene expression in chronic rhinosinusitis.
AB  - BACKGROUND: Epithelial hyperplasia and mucosal infiltration of leukocytes are
      common features of chronic rhinosinusitis. The epithelium can produce
      chemoattractant cytokines that may contribute to leukocyte infiltration in
      rhinosinusitis. OBJECTIVE: We sought to determine whether mucosal IL-8 gene
      expression is increased in chronic rhinosinusitis and to relate IL-8 gene
      expression to disease severity. METHODS: We used both a noncompetitive and a
      quantitative, competitive reverse transcription-polymerase chain reaction to
      examine IL-8 gene expression in samples of sinus mucosal tissue obtained during
      surgery from 22 patients with chronic rhinosinusitis and 9 normal control
      subjects. IL-8 gene expression was related to disease severity assessed by sinus
      computed tomography (CT) scores and to symptom scores assessed by means of a
      questionnaire. RESULTS: Sinus mucosal IL-8 gene expression was not detected in
      any of the control subjects but was present in 12 of 22 (55%) patients with
      rhinosinusitis. Sinus CT scores and symptom scores were both significantly higher
      in patients with positive mucosal IL-8 gene expression than in subjects with no
      detectable IL-8 gene expression. Positive IL-8 gene expression was not predicted
      by history of prior surgery nor by atopic or asthmatic status. In 9 subjects with
      positive IL-8 gene expression, levels of mRNA expression, assessed by competitive
      reverse transcription-polymerase chain reaction, correlated significantly (rho =
      0.72, P <.05) with sinus CT scores. CONCLUSION: Sinus mucosal expression of the
      gene for IL-8 is increased in patients with chronic rhinosinusitis, and the level
      of IL-8 gene expression correlates with disease severity.

PMID- 10069872
TI  - Direct expenditures for the treatment of allergic rhinoconjunctivitis in 1996,
      including the contributions of related airway illnesses.
AB  - BACKGROUND: Previous estimates of the national economic burden of allergic
      rhinoconjunctivitis (AR/AC) have relied on data analyses in which AR/AC was the
      primary International Classification of Diseases-ninth revision-Clinical
      Modification (ICD-9-CM)-coded diagnosis. These studies ignore the costs when
      AR/AC was a secondary diagnosis to other disorders such as asthma and sinusitis.
      OBJECTIVE: We sought to determine the national direct cost of illness for AR/AC.
      METHODS: An expert panel used the Delphi technique to estimate the proportion of
      visits coded by other primary ICD-9-CM diagnoses in which AR/AC was a significant
      secondary comorbid condition. The costs of this proportion were deemed to be
      "attributable" to AR/AC and were added to the costs when allergic rhinitis and
      allergic conjunctivitis were the primary diagnoses. RESULTS: The cost when AR/AC
      was the primary diagnosis was $1.9 billion (in 1996 dollars). The cost when AR/AC
      was a secondary diagnosis was estimated at $4.0 billion, giving an estimate of
      $5.9 billion for the overall direct medical expenditures attributable to AR/AC.
      Outpatient services (63%, $3.7 billion), medications (25%, $1.5 billion), and
      inpatient services (12%, $0.7 billion) accounted for the expenditures. Children
      12 years and younger accounted for $2.3 billion (38.0%). CONCLUSION: Upper airway
      allergy is an expensive disease process because of its readily apparent
      manifestations as AR/AC and its contribution to other airway disorders.

PMID- 10069873
TI  - Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis,
      and other airway disorders.
AB  - BACKGROUND: There have been no recent assessments of the economic burden of
      sinusitis in the peer-reviewed literature. OBJECTIVE: We sought to estimate the
      1996 total direct health care expenditures for the treatment of sinusitis.
      METHODS: This study determined (1) direct expenditures of medical and surgical
      encounters in which sinusitis was the primary diagnosis and (2) attributable
      expenditures when related airway diseases were the primary diagnosis and
      sinusitis was a comorbid condition. An expert panel used the Delphi consensus
      building technique to determine the proportions for the latter. RESULTS: Overall
      health care expenditures attributable to sinusitis in 1996 were estimated at $5.8
      billion, of which $1.8 billion (30.6%) was for children 12 years or younger. A
      primary diagnosis of acute or chronic sinusitis accounted for 58.7% of all
      expenditures ($3.5 billion). About 12% each of the costs for asthma and chronic
      otitis media and eustachian tube disorders were attributed to diagnosis and
      treatment of comorbid sinusitis. Nearly 90% of all expenditures ($5.1 billion)
      were associated with ambulatory or emergency department services. CONCLUSION: The
      economic burden of sinusitis in the United States is significant. However, the
      limitations of this type of evaluation suggest the $5.8 billion amount may be an
      underestimate of the true direct costs.

PMID- 10069874
TI  - Childhood environment and adult atopy: results from the European Community
      Respiratory Health Survey.
AB  - BACKGROUND: Previous literature has indicated that environmental exposures in
      childhood influence development of atopic sensitization. OBJECTIVE: We sought to
      study the association between childhood environment and adult atopy. METHODS:
      Thirteen thousand nine hundred thirty-two subjects aged 20 to 44 years from 36
      areas in Europe, New Zealand, the United States, and Australia took part in the
      European Community Respiratory Health Survey, answering interviewer-led
      questionnaires and providing blood tests for measurement of specific IgE to
      grass, house dust mite, cat, and Cladosporium allergens. RESULTS: Atopy was
      negatively associated with family size (OR = 0. 93; 95% CI = 0.90-0.96 per 1
      sib), partly attributable to an independent protective effect of a greater number
      of brothers (OR = 0.92; 95% CI = 0.89-0.95 per 1 brother). Accounting for total
      number of siblings, no further influence was detected for number of older or
      younger siblings. Bedroom sharing was associated with a lower prevalence of
      atopy, particularly to cat allergen. A protective effect of family size and
      bedroom sharing could only be detected in subjects reporting no parental allergy
      (family size, test for interaction P =.012). The presence of a dog in the home in
      childhood was negatively associated with adult atopy (OR = 0.85, 95% CI = 0. 78
      0.92), an effect that remained after adjustment for parental allergy, sibling
      allergy, and adult pet ownership. CONCLUSION: Subjects from large families with
      brothers, shared bedrooms, and dogs in childhood were less often atopic as
      adults. Our findings are consistent with the hypothesis that infectious agents
      could inhibit development of atopy during childhood. However, in subjects with a
      strong genetic predisposition, environmental factors in childhood are possibly of
      less importance.

PMID- 10069875
TI  - Mechanisms of glucocorticoid reduction in asthmatic subjects treated with
      intravenous immunoglobulin.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has been used as an oral
      glucocorticoid (GC)-sparing agent in patients with steroid-dependent asthma.
      Despite its use, little is known regarding its mechanism of action. OBJECTIVE: We
      sought to determine whether the GC-sparing effects of IVIG in severe asthma are
      related to improved GC receptor (GCR)-binding affinity and subsequent enhanced GC
      sensitivity. METHODS: In an open-label study, 11 steroid-dependent asthmatic
      subjects (6 GC-insensitive, 5 GC-sensitive) received monthly infusions of IVIG (2
      g/kg) for 6 months. Peak expiratory flow rates and oral GC dose were recorded
      daily, and spirometry was performed monthly. Blood was drawn for lymphocyte
      stimulation assays and GCR assays at baseline and after 3 and 6 months of
      therapy. Lymphocytes were stimulated ex vivo with PHA in the presence and absence
      of IVIG and increasing concentrations of dexamethasone (DEX). RESULTS: IVIG
      resulted in significant reductions in oral GC dose (P <.02), number of GC bursts
      (P =.033), and hospitalizations (P =.001) after 6 months of IVIG. Those with GC
      insensitive asthma responded equally well to IVIG as those with GC-sensitive
      asthma. Associated with the improved clinical efficacy, IVIG acted
      synergistically with DEX in suppressing lymphocyte activation as measured by a
      shift in the DEX dose-response curve by 1 log-fold (P =.03). IVIG therapy was
      also associated with significantly improved GCR-binding affinity (P =.01).
      CONCLUSIONS: IVIG resulted in significant reductions in oral GC requirements and
      hospitalizations in a group of patients with severe asthma, with IVIG being as
      effective in patients with GC-insensitive asthma as in patients with GC-sensitive
      asthma. IVIG therapy acted synergistically with DEX in suppressing lymphocyte
      activation and significantly improved GCR-binding affinity after 3 and 6 months
      of therapy.

PMID- 10069877
TI  - A randomized controlled trial of a pediatric asthma outreach program.
AB  - BACKGROUND: Previous studies have shown that asthma education and case management
      may reduce asthma emergency care, hospitalizations, and expenditures. OBJECTIVE:
      We sought to study the effect of an asthma outreach program (AOP), a team-based,
      case-management intervention, on emergency ward (EW) and hospital use. METHODS:
      Fifty-seven patients aged 1 to 15 years with the diagnosis of asthma based on the
      usual clinical practice criteria who were continuously enrolled in a staff-model
      health maintenance organization for a period of at least 2 consecutive years were
      randomized into 2 intervention groups. The control group received a single
      intensive asthma education intervention, and the AOP group received the same
      initial education but then was followed-up by an asthma case management nurse
      throughout the intervention period. RESULTS: EW visits, hospitalizations, and
      total outside-of-health-plan expenditures (consisting of EW and hospital
      expenses, as well as miscellaneous costs, such as ambulance, durable medical
      equipment, tertiary referrals, and home care) were assessed from claims filed for
      a year before and after enrollment. Control group patients experienced
      significant reductions in EW visits (39%), hospitalizations (43%), and outside-of
      health-plan costs (28%), possibly as a result of the baseline educational
      intervention received by all enrolled patients, in conjunction with regression to
      the mean. AOP group patients experienced significant reductions in EW visits,
      (73%, P =.0002), hospitalizations (84%, P =.0012), and outside-of-health-plan use
      (82%, P <.0001). When compared with the control group, AOP group patients
      demonstrated additional significant reductions in EW visits (57%, P <.05),
      hospitalizations (75%, P <.05), and outside-of-health-plan use (71%, P <.001).
      Estimates of direct savings to the health plan ranged from $7.69 to $11.67 for
      every dollar spent on the AOP nurse's salary, depending on assumptions.
      CONCLUSIONS: Asthma patients in a staff-model health maintenance organization
      decreased their resource use between 57% to 75% by participation in an AOP as
      compared with a randomized control group receiving only an educational
      intervention. Substantial savings were achieved compared with the cost of the AOP
      nurse.

PMID- 10069876
TI  - Sustained bronchoprotection, bronchodilatation, and symptom control during
      regular formoterol use in asthma of moderate or greater severity. The Canadian
      FO/OD1 Study Group.
AB  - BACKGROUND: Recent studies have raised concern that regular inhalation of beta2 
      agonists may cause a worsening of asthma control compared with on-demand dosing
      regimens. OBJECTIVE: The objective of this study was to compare the effect of
      twice daily formoterol (Foradil), 4 times daily albuterol, and on-demand
      albuterol on bronchial hyperresponsiveness (BHR), lung function measurements,
      symptoms, and other indicators of disease control over 6 months inpatients with
      asthma of moderate or greater severity receiving concomitant inhaled
      corticosteroids. We also looked for occurrence of rebound BHR on discontinuation
      of treatment. METHODS: This was a multicenter, parallel-group, double-blind,
      clinical trial. Methacholine PC20 was the primary outcome variable. Other outcome
      variables included symptom scores, use of rescue medication, morning peak
      expiratory flow (PEF), serial FEV1 measurements, and asthma exacerbations.
      RESULTS: Of the 271 randomized patients, 217 completed the study. Formoterol was
      significantly superior to on-demand albuterol with regard to methacholine PC20,
      FEV1, PEF, symptom scores, and use of rescue medication at each measured time
      point/interval. Regular albuterol was superior to on-demand albuterol with regard
      to PC20 and FEV1, but not PEF or various clinical scores. After a small drop in
      the magnitude of bronchoprotection and bronchodilatation occurring shortly after
      randomization, there was no evidence of progressive tolerance to either regular
      treatment for any of the measured variables or of rebound increase in BHR 2 days
      after the end of treatment. The formoterol group had the lowest number of
      exacerbation days, as defined by high intake of rescue bronchodilator and/or
      symptom scores, whereas the number of exacerbations requiring increased
      corticosteroid coverage was similar in the 3 groups. CONCLUSION: In patients with
      asthma of moderate or greater severity receiving inhaled corticosteroids,
      formoterol taken twice daily resulted in superior bronchoprotection,
      bronchodilatation, and clinical control compared with on-demand albuterol over 6
      months. Four times daily albuterol was superior to on-demand albuterol for only
      some of the end points. Progressive tolerance and a rebound increase in BHR on
      discontinuation of beta-agonists were not found

PMID- 10069878
TI  - Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in
      the nasal mucosa after nasal allergen provocation.
AB  - BACKGROUND: Allergic inflammation is regulated by the local production and
      release of several cytokines. OBJECTIVES: This study was designed to assess the
      changes in mRNA cytokine-positive cells after allergen provocation and to compare
      these cytokines with tissue eosinophilia as a marker of allergic inflammation.
      METHODS: A grass pollen allergen provocation study was conducted in autumn, out
      of the hay fever season. Nasal mucosal biopsy specimens were taken before
      provocation and 1 hour, 24 hours, and 1 week after allergen provocation.
      Eosinophils and mRNA-positive cells (in situ hybridization for IL-2, IL-3, IL-4,
      IL-5, IL-6, IL-8, IL-10, IL-13, IFN-gamma, RANTES, and TNF-alpha) were assessed
      in the biopsy specimens. RESULTS: After allergen provocation, an increase in cell
      number was found for eosinophils and cells expressing mRNA for the chemokines IL
      8 and RANTES and for the TH2 cytokines IL-10 and IL-13. Significant correlations
      were found between eosinophils and RANTES and eosinophils and IFN-gamma in the
      early phase and between eosinophils and IL-5 and eosinophils and RANTES in the
      late phase. The increase in eosinophils and IL-10 and IL-13 mRNA-positive cells
      could still be observed 1 week after allergen provocation. CONCLUSIONS: Nasal
      allergen provocation induced significant tissue eosinophilia and a significant
      increase in IL-8, IL-13, and RANTES mRNA-positive cells. A significant increase
      in eosinophils and IL-10 and IL-13 mRNA-positive cells compared with baseline can
      still be observed 1 week after a single allergen provocation.

PMID- 10069879
TI  - Differential regulation of antigen-induced IL-4 and IL-13 generation from T
      lymphocytes by IFN-alpha.
AB  - BACKGROUND: IL-4 and IL-13 are related cytokines with similar functional
      properties. Differential regulation of IL-4 and IL-13 has not been described.
      OBJECTIVE: We have examined the effects of IFN-alpha on antigen-driven
      proliferation, IL-4 generation, and IL-13 generation from human PBMCs and T-cell
      clones. METHODS: Proliferation was assessed by 3H-thymidine incorporation.
      Cytokine generation was assessed by reverse transcription PCR and ELISA.
      Messenger RNA stability was assessed in the presence of actinomycin D. RESULTS:
      IFN-alpha induced a concentration-dependent inhibition of antigen-driven
      proliferation of TH1 and TH2 clones (median effective concentration, 150 to 200
      U/mL); the sensitivity of TH1 and TH2 clones to IFN-alpha was not significantly
      different (P =.6). IFN-alpha induced an analogous concentration-dependent
      inhibition of antigen-driven IL-13 generation from TH1 and TH2 clones (median
      effective concentration, 100 U/mL); this effect was evident by 12 hours of
      culture and persisted beyond 48 hours. However, IL-4 generation from TH2 clones
      was insensitive to IFN-alpha at all concentrations and times tested (1 to 10,000
      U/mL). A similar inhibitory effect of IFN-alpha on mitogen-driven proliferation
      and IL-13 generation from PBMCs was demonstrated; once again, IL-4 generation
      from PBMCs was insensitive to IFN-alpha. IL-13 mRNA stability was unaffected by
      IFN-alpha, suggesting transcriptional regulation. CONCLUSION: IFN-alpha
      differentially regulates antigen-stimulated IL-4 and IL-13 generation.

PMID- 10069880
TI  - Predominant TH1 cytokine pattern in peripheral blood from subjects with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Previous studies have provided evidence for an inflammatory process
      in the large airways of subjects with chronic obstructive pulmonary disease
      (COPD), consisting predominantly of activated T cells. No data are available on
      the TH1 /TH2 T-cell cytokine pattern in this disease. OBJECTIVE: We sought to
      characterize the TH1 /TH2 T-cell cytokine pattern in subjects with COPD. METHODS:
      We examined the IFN-gamma and IL-4 expression in peripheral blood CD4+ and CD8+ T
      cells from 20 patients with COPD and 25 control subjects by using a flow
      cytometric method of intracellular cytokine detection. We also examined the
      expression of 2 surface activation markers (CD25 and HLA-DR) on peripheral blood
      CD4+ and CD8+ T cells. RESULTS: There was an increased percentage of IFN-gamma
      producing cells (30.3% [range, 12.9% to 60.4%] vs 19.1% [range, 4% to 31.2%], P
      =.003) and a decreased percentage of IL-4-producing cells (4.55% [range, 0.6% to
      11.3%] vs 9.5% [2.1% to 21.3%], P =.0008) among peripheral blood CD4+ T cells
      from the patients with COPD compared with control subjects. There was no
      significant difference between the 2 groups in the percentage of peripheral blood
      CD8+ T cells producing IFN-gamma or IL-4 or in the percentage of peripheral blood
      CD4+ and CD8+ T cells expressing CD25 and HLA-DR. CONCLUSION: These findings
      provide evidence for a TH1 -like immune response of peripheral blood CD4+ T cells
      in subjects with COPD.

PMID- 10069881
TI  - Inhaled IL-5 increases concentrations of soluble intracellular adhesion molecule
      1 in sputum from atopic asthmatic subjects.
AB  - BACKGROUND: Both IL-5 and intracellular adhesion molecule-1 (ICAM-1) have been
      shown to play important roles in the production of allergic inflammation,
      including atopic asthma. OBJECTIVE: The aim of this study was to investigate the
      effects of recombinant human IL-5 on changes of soluble (s) ICAM-1 concentrations
      in induced sputum from allergic asthmatic subjects. METHODS: In a randomized,
      double-blind, placebo-controlled study design, 8 nonsmoking patients with
      allergic asthma and 6 nonallergic normal subjects were administered recombinant
      human IL-5 by nebulization, and the concentrations of sICAM-1 in induced sputum
      from each subject were determined before and at 2, 24, 48, and 72 hours after
      inhalation. RESULTS: sICAM-1 levels in sputum within the control group did not
      appear to change from baseline at any time throughout the study. In allergic
      asthmatic subjects vehicle challenge was not able to cause any changes in sputum
      sICAM-1 concentrations. However, there were increases in sputum sICAM-1
      concentrations after IL-5 inhalation, which increased with time to significantly
      greater levels than those at baseline, reaching a maximum at 48 hours and lasting
      no less than 72 hours. The concentrations of sICAM-1 in sputum after IL-5
      challenge exceeded levels that could be accounted for by passive transudation
      from the circulation on the basis of the magnitude of increases in sputum albumin
      concentration. CONCLUSION: Our results indicated that IL-5 inhalation was capable
      of inducing an elevation of sputum sICAM-1 concentration by stimulating its local
      release in allergic asthmatic, but not in nonallergic normal, subjects.

PMID- 10069882
TI  - The kinetics of change in cytokine production by CD4 T cells during conventional
      allergen immunotherapy.
AB  - BACKGROUND: The effect of conventional allergen immunotherapy on allergen
      specific T lymphocyte cytokine production is incompletely understood,
      particularly during the initial phase of treatment. OBJECTIVE: The purpose of
      this study was to prospectively follow the kinetics of change in CD4(+) T cell
      cytokine secretion during the course of conventional immunotherapy. METHODS: Six
      allergic individuals were treated with extracts of Dermatophagoides
      farinae/Dermatophagoides pteronyssinus or with rye grass pollen (Lolium perenne)
      allergen, but not both, by using an internally controlled conventional
      immunotherapy protocol. CD4(+) T cells from peripheral blood were examined in
      vitro at varying intervals after the initiation of immunotherapy by stimulation
      with D farinae or L perenne group I antigen. The quantity of IL-4 and IFN-gamma
      produced and its relationship to clinical improvement was determined. RESULTS:
      The ratio of allergen-specific IL-4/IFN-gamma production by CD4(+) T cells from 4
      of 6 individuals receiving immunotherapy greatly increased during the period when
      the dose of allergen was increasing. However, after high-dose maintenance therapy
      was achieved, this ratio decreased in subjects responding clinically to, but not
      in those failing, immunotherapy. In addition, late-phase skin reactions and
      allergen-specific IgE levels in responding, but not in nonresponding, subjects
      diminished over the course of immunotherapy. CONCLUSION: Conventional
      immunotherapy may initially exacerbate allergic disease by increasing allergen
      specific IL-4 and allergen-specific IgE production. Later clinical improvement is
      associated with a reduction in allergen-specific IL-4 production and in allergen
      specific serum IgE.

PMID- 10069883
TI  - Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of
      asthmatic and nonasthmatic individuals.
AB  - BACKGROUND: Although an eosinophilic infiltrate has been observed in the small
      airways of asthmatic individuals, the mechanisms responsible for cellular
      recruitment in the lung periphery remain to be clarified. Eotaxin and monocyte
      chemotactic protein (MCP)-4 are 2 eosinophil-associated chemokines shown to be
      upregulated at sites of allergic inflammation. However, their expression within
      the small airways of asthmatic individuals remains to be elucidated. OBJECTIVE:
      We sought to determine the expression of eotaxin and MCP-4 in the peripheral
      airways and parenchyma of lungs of subjects with asthma and to assess their
      relationship to the numbers of resident eosinophils. METHODS: We examined
      surgically resected lung tissue from 6 asthmatic and 10 nonasthmatic subjects for
      the presence of eotaxin and MCP-4 mRNA by in situ hybridization. Chemokine mRNA
      expression was examined with respect to the numbers of eosinophils within the
      airways, as detected by immunocytochemistry for major basic protein. RESULTS:
      Numbers of chemokine mRNA-positive cells were significantly increased in the
      large and small airways of asthmatic subjects compared with nonasthmatic
      subjects. Although eotaxin and MCP-4 mRNA were widely expressed in the lungs of
      subjects with asthma, their expression was particularly evident within the
      bronchial epithelium and inflammatory cells. In the airways of the asthmatic
      individuals, the expression of eotaxin mRNA was significantly correlated to the
      numbers of eosinophils present. CONCLUSION: There is an increased expression of
      eotaxin and MCP-4 mRNA within the peripheral airways of lungs of asthmatic
      subjects, suggesting that these chemokines contribute to the small airways and
      peripheral lung inflammation in asthma.

PMID- 10069884
TI  - Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria:
      comparison of patients with and without anti-FcepsilonRI or anti-IgE
      autoantibodies.
AB  - BACKGROUND: Previous studies defining the histopathologic features of patients
      with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain
      duration and before the identification of functional autoantibodies against
      FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients
      with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory
      infiltrate in the wheals of patients with CIU and to detect differences between
      patients with and without autoantibodies. METHODS: Immunohistochemistry was used
      to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated
      eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for
      less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as
      in biopsy specimens from the skin of 12 healthy control subjects. Patients were
      identified as having functional autoantibodies on the basis of their serum-evoked
      histamine release in vitro from the basophils of 2 healthy donors. RESULTS:
      EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in
      greater numbers in wheals undergoing biopsy at less than 4 and greater than 12
      hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12)
      had significantly more EG2(+) cells in wheals of greater than 12 hours' duration
      than patients with autoantibodies (n = 10; P =.02). There was no other difference
      between patients with and without autoantibodies in the cutaneous cellular
      infiltrate. CONCLUSION: Neutrophil and eosinophil accumulation occurs early in
      the evolution of a wheal in patients with CIU, but eosinophil activation may
      occur later or be more persistent in patients without autoantibodies.

PMID- 10069885
TI  - Fungal extracellular polysaccharides in house dust as a marker for exposure to
      fungi: relations with culturable fungi, reported home dampness, and respiratory
      symptoms.
AB  - BACKGROUND: Epidemiologic studies have demonstrated an association between indoor
      fungal growth and respiratory symptoms. However, in only a few studies was fungal
      exposure actually measured. OBJECTIVE: The purpose of this study was to evaluate
      the measurement by enzyme immunoassay of extracellular polysaccharides of
      Aspergillus and Penicillium species (EPS-Asp/Pen ) in house dust as a marker for
      fungal exposure and to study the relations between EPS-Asp/Pen levels and home
      dampness and respiratory symptoms in children. METHODS: Extracts of house dust
      samples from bedroom and living room floors and mattresses from homes of 31
      children with chronic respiratory symptoms and 29 children with no chronic
      respiratory symptoms were analyzed for EPS-Asp/Pen. RESULTS: EPS-Asp/Pen were
      readily detectable (40 to 46,513 nanogram equivalent/g dust) in 161 house dust
      extracts, with highest concentrations in living room floor dust. EPS-Asp/Pen
      levels were 2 to 3 times higher on carpeted floors than on smooth floors. EPS
      Asp/Pen were significantly correlated with total culturable fungi (r = 0.3 to
      0.5) and with house dust mite allergens (r = 0.3 to 0.5). EPS-Asp/Pen levels in
      living room floor dust were positively associated with occupant-reported home
      dampness. This was not observed for EPS-Asp/Pen in bedroom floor and mattress
      dust. EPS-Asp/Pen levels in living room floor dust were positively associated
      with respiratory symptoms. EPS-Asp/Pen in bedroom floor and mattress dust showed
      a reversed association with respiratory symptoms, possibly because of allergen
      avoidance measures taken in the bedroom. CONCLUSION: The enzyme immunoassay for
      fungal EPS-Asp/Pen may be a useful method for exposure assessment of indoor
      fungi.

PMID- 10069886
TI  - Results of the National Cooperative Inner-City Asthma Study (NCICAS)
      environmental intervention to reduce cockroach allergen exposure in inner-city
      homes.
AB  - BACKGROUND: Cockroach allergen is important in asthma. Practical methods to
      reduce exposure are needed. OBJECTIVE: We sought to evaluate the effectiveness of
      house cleaning and professional extermination on lowering cockroach antigen
      levels in inner-city dwellings. METHODS: As part of the National Cooperative
      Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children
      who had positive skin test responses to cockroach allergen consented to a
      professional home extermination with 2 applications of a cockroach insecticide
      (Abamectin, Avert) combined with directed education on cockroach allergen
      removal. On a random subset of 48 homes undergoing cockroach extermination in the
      intervention group, Bla g 1 was measured in settled dust from the kitchen,
      bedroom, and TV/living room. The first sample was collected 1 week before
      extermination, with additional samples after the exterminations at approximately
      2, 6, and 12 months after the first sample. Self-reported problems with
      cockroaches were collected at baseline and after 12 months of follow-up in both
      the intervention and control group. RESULTS: The geometric mean kitchen level of
      Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels
      (68.7 U/g, P <.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a
      similar pattern, but only the decrease from preextermination to 6-month levels
      was significant (86.8% vs 64.3%, P <.05). By the 12-month visit, the allergen
      burden had returned to or exceeded baseline levels. Except for an increase in the
      bedroom at 2 months (8.9 U/g vs 11.1 U/g, P <.05), no other significant change
      was seen. Only about 50% of the families followed the cleaning instructions; no
      greater effect was found in these homes. Self-reported problems with cockroaches
      showed no difference between the intervention and control group after 1 year of
      follow-up. CONCLUSIONS: Despite a significant, but short-lived, decrease the
      cockroach allergen burden remained well above levels previously found to be
      clinically significant.

PMID- 10069887
TI  - Class I chitinases as potential panallergens involved in the latex-fruit
      syndrome.
AB  - BACKGROUND: Latex-fruit cross-sensitization has been fully demonstrated. However,
      the antigens responsible for this "latex-fruit syndrome" have not been
      identified. We have recently shown that class I chitinases are relevant chestnut
      and avocado allergens. OBJECTIVE: We sought to evaluate the in vivo and in vitro
      reactions of purified chestnut and avocado chitinases in relation to the latex
      fruit syndrome. METHODS: From a latex-allergic population, eighteen patients
      allergic to chestnut, avocado, or both were selected. Skin prick tests (SPTs)
      were performed with crude chestnut and avocado extracts, chitinase-enriched
      preparations, and purified class I and II chitinases from both fruits. CAP
      inhibition assays with the crude extracts and purified proteins were carried out.
      Immunodetection with sera from patients with latex-fruit allergy and immunoblot
      inhibition tests with a latex extract were also performed. Eighteen subjects
      paired with our patients and 15 patients allergic to latex but not food were used
      as control groups. RESULTS: The chestnut class I chitinase elicited positive SPT
      responses in 13 of 18 patients with latex-fruit allergy (72%), and the avocado
      class I chitinase elicited positive responses in 12 of 18 (67%) similarly
      allergic patients. By contrast, class II enzymes without a hevein-like domain did
      not show SPT responses in the same patient group. Each isolated class I chitinase
      reached inhibition values higher than 85% in CAP inhibition assays against the
      corresponding food extract in solid phase. Immunodetection of the crude extracts
      and the purified class I chitinases revealed a single 32-kd band for both
      chestnut and avocado. Preincubation with a natural latex extract fully inhibited
      the IgE binding to the crude extracts, as well as to the purified chestnut and
      avocado class I chitinases. CONCLUSION: Chestnut and avocado class I chitinases
      with an N-terminal hevein-like domain are major allergens that cross-react with
      latex. Therefore they are probably the panallergens responsible for the latex
      fruit syndrome.

PMID- 10069888
TI  - Lipid-transfer proteins are relevant allergens in fruit allergy.
AB  - BACKGROUND: Allergy to apple and Prunus fruits is frequently associated with
      birch pollinosis, with the principal cross-reacting allergens involved being
      members of the Bet v 1 family. However, a major 13-kd component,
      nonimmunologically related to Bet v 1, has been implicated as allergen in
      patients allergic to Prunoideae fruit but not to birch pollen. OBJECTIVE: We
      sought to isolate and characterize the 13-kd allergen present in apple and peach.
      METHODS: Sera from patients allergic to both fruits were selected on the basis of
      clinical symptoms, skin prick tests responses, and specific IgE levels. Allergens
      were purified by reverse-phase HPLC and characterized by N-terminal amino acid
      sequencing, MALDI analysis, specific IgE immunodetection, and immunoblot
      inhibition assays. RESULTS: A 13-kd protein band was recognized in crude apple
      and peach extracts by 9 of 10 and 10 of 10 sera from patients allergic to fruit,
      respectively. The isolation and characterization of the corresponding allergens
      allowed their identification as lipid-transfer proteins, with a molecular mass of
      9058 d for the apple protein and 9138 d for the peach protein. Both purified
      allergens were recognized by sera from patients allergic to fruit and fully
      inhibited the IgE binding by the 13-kd component present in the 2 crude fruit
      extracts. CONCLUSION: Lipid-transfer proteins are relevant apple and peach
      allergens and, considering their ubiquitous distribution in tissues of many plant
      species, could be a novel type of panallergen of fruits and vegetables.

PMID- 10069889
TI  - The major allergen of peach (Prunus persica) is a lipid transfer protein.
AB  - BACKGROUND: Allergy to fresh fruits and vegetables is mostly observed in subjects
      with pollinosis, especially from birch, because of cross-reacting allergens in
      vegetable foods and pollens. However, allergic reactions to fruits, specifically
      Rosaceae fruits, have been reported in subjects without pollinosis. OBJECTIVE:
      This study evaluated the pattern of IgE reactivity, identifying the allergen
      responsible in 2 groups of patients with oral allergy syndrome to peach with or
      without birch pollinosis. METHODS: The allergenic components of peach were
      detected by SDS-PAGE and immunoblotting. The major peach allergen was purified by
      HPLC with a cation-exchange column followed by gel filtration chromatography. Its
      IgE-binding capacity and its homology with the protein of the crude extract were
      demonstrated by immunoblotting inhibition techniques. To better characterize this
      allergen, periodic acid-Schiff stain and isoelectrofocusing were used. The amino
      acid sequencing was done with a gas-phase sequencer. RESULTS: SDS-PAGE and
      immunoblotting of the 15 patients allergic to peach, 8 without and 7 with birch
      pollinosis, showed that they all recognized a protein with a molecular weight of
      9 kd. This was the only allergen recognized by patients not sensitized to pollen,
      whereas the birch pollen-sensitive patients had IgE binding to other allergenic
      proteins at higher molecular weights. The purified 9-kd protein retained its IgE
      binding capacity, was negative to periodic acid-Schiff stain, and had an
      isoelectric point value of greater than 9. A search in the Swiss Prot Bank showed
      this was a lipid transfer protein, belonging to a group of molecules involved in
      the defensive system of plants. CONCLUSIONS: The major allergen of peach is a 9
      kd protein belonging to the group of lipid transfer proteins. This is the only
      allergen recognized by patients allergic to peach but not sensitized to birch
      pollen.

PMID- 10069890
TI  - Macrophage-derived chemokine induces human eosinophil chemotaxis in a CC
      chemokine receptor 3- and CC chemokine receptor 4-independent manner.
AB  - BACKGROUND: Chemokines are believed to contribute to selective cell recruitment.
      Macrophage-derived chemokine (MDC) is a CC chemokine that causes chemotaxis of
      dendritic cells, monocytes, and activated natural killer cells. MDC binds to CC
      chemokine receptor 4 (CCR4) but not to CCR1, CCR2, CCR3, CCR5, CCR6, or CCR7.
      OBJECTIVE: Our aim was to determine the in vitro activity of MDC on human
      eosinophils by using chemotaxis and calcium flux assays. METHODS: Eosinophils
      were purified from peripheral blood of allergic donors, and chemotactic activity
      of MDC and other CC chemokines was compared in microchemotaxis chamber assays.
      The role of CCR3 in these assays was determined by using a CCR3-blocking
      antibody. Measurements of cytosolic Ca++ mobilization were performed by using
      fura-2AM labeling, with eosinophils and cell lines transfected with CCR3 or CCR4.
      Eosinophil expression of CCR3 and CCR4 mRNA was determined by using RT-PCR.
      RESULTS: MDC (0.1 to 100 nmol/L) caused dose-dependent chemotaxis of purified
      human eosinophils (maximum approximately 3-fold control). Compared with other CC
      chemokines, the potency and efficacy for eosinophil chemotaxis were similar for
      MDC and eotaxin but were less than that observed for RANTES, monocyte
      chemoattractant protein (MCP)-4, and eotaxin-2. Although MDC can act by means of
      CCR4, RT-PCR analysis failed to reveal CCR4 mRNA in eosinophils. Effects of MDC
      on eosinophils was also independent of CCR3, as a blocking mAb to CCR3 failed to
      inhibit MDC-induced chemotaxis. Furthermore, CCR3-transfected human embryonic
      kidney cells labeled with Fura-2AM exhibited a rapid rise in intracellular free
      calcium after stimulation with eotaxin, eotaxin-2, or MCP-4, but not with MDC.
      Eosinophils cultured for 72 hours in 10 ng/mL IL-5 also demonstrated increased
      intracellular free calcium after stimulation with eotaxin-2 or MCP-4, but not
      with up to 100 nmol/L MDC. CONCLUSION: MDC is a CCR3- and CCR4-independent
      activator of eosinophil chemotaxis, but it does not appear to elicit measurable
      cytosolic calcium elevations during these responses. MDC appears to act by means
      of another receptor in addition to CCR4 and may therefore contribute to
      eosinophil accumulation without working through CCR1 to CCR7.

PMID- 10069891
TI  - Drug-induced lupus in a child after treatment with zafirlukast (Accolate).

PMID- 10069892
TI  - Churg-Strauss syndrome after corticosteroid withdrawal in an asthmatic patient
      treated with pranlukast.

PMID- 10069893
TI  - Assessment of the AirWatch lung function monitoring system. Asthma Clinical
      Research Network (ACRN).

PMID- 10069895
TI  - Pathophysiology and pharmacotherapy of allergic rhinitis. Foreword.

PMID- 10069896
TI  - Mediators of inflammation and the inflammatory process.
AB  - A complex interplay of inflammatory cells and chemical mediators is responsible
      for allergic inflammation. It is now understood that the allergic reaction
      consists of an early-phase response involving mast cell degranulation with the
      release of histamine and a late-phase response characterized by the migration of
      inflammatory cells. This review provides a summary of the early- and late-phase
      events associated with allergic inflammation and an overview of the principal
      chemical mediators involved in the inflammatory process.

PMID- 10069897
TI  - Clinical manifestations of the release of histamine and other inflammatory
      mediators.
AB  - This article reviews the symptoms that are characteristic of the early- and late
      phase allergic reaction. Each of the cardinal symptoms of seasonal allergic
      rhinitis (sneezing, pruritus, rhinorrhea, congestion) is discussed, as is the
      role of various chemical mediators in the expression of these clinical
      manifestations.

PMID- 10069898
TI  - Ideal pharmacotherapy for allergic rhinitis.
AB  - The characteristics of the "ideal" pharmacotherapeutic agent for managing the
      symptoms of seasonal allergic rhinitis and the advantages and disadvantages of
      the pharmacotherapeutic agents that are currently available are reviewed.
      Decongestants, mast cell stabilizers, anticholinergics, intranasal steroids, and
      oral antihistamines and their place in the therapeutic armamentarium of the
      clinician are discussed.

PMID- 10069899
TI  - Use of nasal steroids in managing allergic rhinitis.
AB  - Intranasal steroids are highly effective drugs for treating patients with
      allergic rhinitis. First-line use of intranasal steroids is becoming increasingly
      common, and intranasal steroids can be used alone or in combination with other
      therapies to achieve optimal improvement in rhinitis symptoms. The major adverse
      effect of intranasal steroids is local irritation. This article reviews the
      mechanism of action of corticosteroids, the effects of intranasal steroids on
      chemical mediators of inflammation, and the risks and benefits associated with
      their use.

PMID- 10069900
TI  - Pros and cons of the use of antihistamines in managing allergic rhinitis.
AB  - Histamine H1 -receptor antagonists are generally considered first-line therapy
      for the management of allergic rhinitis. Other than histamine antagonism, several
      of the second-generation antihistamines have also shown inhibitory effects on
      chemical mediators of inflammation such as leukotrienes, prostaglandins, and
      kinins. This article reviews the pharmacology, clinical use, and side effect
      profiles of the commonly used H1 -receptor antagonists.

PMID- 10069901
TI  - Management of allergic rhinitis with a combination antihistamine/anti
      inflammatory agent.
AB  - Azelastine nasal spray is a topical antihistamine treatment for the symptoms of
      seasonal allergic rhinitis. Besides histamine antagonism, azelastine affects
      other chemical mediators of the inflammatory response including leukotrienes and
      kinins. This article reviews and discusses the antihistaminic and anti
      inflammatory properties of azelastine and the results of pharmacokinetic studies
      and controlled clinical trials.

PMID- 10069902
TI  - Long-term functional status and quality of life after lower extremity
      revascularization.
AB  - OBJECTIVE: The objective of this study was to assess the longer term (up to 7
      years) functional status and quality of life outcomes from lower extremity
      revascularization. METHODS: This study was designed as a cross-sectional
      telephone survey and chart review at the University of Minnesota Hospital. The
      subjects were patients who underwent their first lower extremity
      revascularization procedure or a primary amputation for vascular disease between
      January 1, 1989, and January 31, 1995, who had granted consent or had died. The
      main outcome measures were ability to walk, SF-36 physical function, SF-12,
      subsequent amputation, and death. RESULTS: The medical records for all 329
      subjects were reviewed after the qualifying procedures for details of the primary
      procedure (62.6% arterial bypass graft, 36.8% angioplasty, 0.6% atherectomy),
      comorbidities (64% diabetics), severity of disease, and other vascular risk
      factors. All 166 patients who were living were surveyed by telephone between June
      and August 1996. At 7 years after the qualifying procedure, 73% of the patients
      who were alive still had the qualifying limb, although 63% of the patients had
      died. Overall, at the time of the follow-up examination (1 to 7.5 years after the
      qualifying procedure), 65% of the patients who were living were able to walk
      independently and 43% had little or no limitation in walking several blocks. In a
      multiple regression model, patients with diabetes and patients who were older
      were less likely to be able to walk at follow-up examination and had a worse
      functional status on the SF-36 and a lower physical health on the SF-12. Number
      of years since the procedure was not a predictor in any of the analyses.
      CONCLUSION: Although the long-term mortality rate is high in the population that
      undergoes lower limb revascularization, the survivors are likely to retain their
      limb over time and have good functional status.

PMID- 10069903
TI  - Prevalence of true vein graft aneurysms: implications for aneurysm pathogenesis.
AB  - BACKGROUND: Circumstantial evidence suggests that arterial aneurysms have a
      different cause than atherosclerosis and may form part of a generalized dilating
      diathesis. The aim of this study was to compare the rates of spontaneous aneurysm
      formation in vein grafts performed either for popliteal aneurysms or for
      occlusive disease. The hypothesis was that if arterial aneurysms form a part of a
      systemic process, then the rates of vein graft aneurysms should be higher for
      patients with popliteal aneurysms than for patients with lower limb ischemia
      caused by atherosclerosis. METHODS: Infrainguinal vein grafting procedures
      performed from 1990 to 1995 were entered into a prospective audit and graft
      surveillance program. Aneurysmal change was defined as a focal increase in the
      graft diameter of 1.5 cm or greater, excluding false aneurysms and dilatations
      after graft angioplasty. RESULTS: During the study period, 221 grafting
      procedures were performed in 200 patients with occlusive disease and 24 grafting
      procedures were performed in 21 patients with popliteal aneurysms. Graft
      surveillance revealed spontaneous aneurysm formation in 10 of the 24 bypass
      grafts (42%) for popliteal aneurysms but in only 4 of the 221 grafting procedures
      (2%) that were performed for chronic lower limb ischemia. CONCLUSION: This study
      provides further evidence that aneurysmal disease is a systemic process, and this
      finding has clinical implications for the treatment of popliteal aneurysms.

PMID- 10069904
TI  - Isolated femoropopliteal bypass graft for limb salvage after failed tibial
      reconstruction: a viable alternative to amputation.
AB  - PURPOSE: Femoropopliteal bypass grafting procedures performed to isolated
      popliteal arteries after failure of a previous tibial reconstruction were
      studied. The results were compared with those of a study of primary isolated
      femoropopliteal bypass grafts (IFPBs). METHODS: IFPBs were only constructed if
      the uninvolved or patent popliteal segment measured at least 7 cm in length and
      had at least one major collateral supplying the calf. When IFPB was performed for
      ischemic lesions, these lesions were usually limited to the digits or small
      portions of the foot. Forty-seven polytetrafluoroethylene grafts and three
      autogenous reversed saphenous vein grafts were used. RESULTS: Ankle brachial
      pressure index (ABI) increased after bypass grafting by a mean of 0.46. Three
      year primary life table patency and limb-salvage rates for primary IFPBs were 73%
      and 86%, respectively. All eight IFPBs performed after failed tibial bypass
      grafts remained patent for 2 to 44 months, with patients having viable, healed
      feet. CONCLUSION: In the presence of a suitable popliteal artery and limited
      tissue necrosis, IFPB can have acceptable patency and limb-salvage rates, even
      when a polytetrafluoroethylene graft is used. Secondary IFPB can be used to
      achieve limb salvage after failed tibial bypass grafting.

PMID- 10069905
TI  - Superficial femoral eversion endarterectomy combined with a vein segment as a
      composite artery-vein bypass graft for infrainguinal arterial reconstruction.
AB  - OBJECTIVE: The purpose of this study was to determine the results of composite
      artery-vein bypass grafting for infrainguinal arterial reconstruction. METHODS:
      This study was designed as a retrospective case series in two tertiary referral
      centers. Forty-eight of 51 patients underwent the procedure of interest for the
      treatment of ischemic skin lesions (n = 42), rest pain (n = 3), disabling
      claudication (n = 1), and infected prosthesis (n = 2). The intervention used was
      infrainguinal composite artery-vein bypass grafting to popliteal (n = 18) and
      infrapopliteal (n = 30) arteries, with an occluded segment of the superficial
      femoral artery prepared with eversion endarterectomy and an autogenous vein
      conduit harvested from greater saphenous veins (n = 43), arm veins (n = 3), and
      lesser saphenous veins (n = 2). The main outcome measures, primary graft patency
      rates, foot salvage rates, and patient survival rates, were described by means of
      the life-table method for a mean follow-up time of 15.5 months. RESULTS: The
      cumulative loss during the follow-up period was 6% and 24% at 6 and 12 months,
      respectively. The primary graft patency rates, the foot salvage rates, and the
      patient survival rates for patients with popliteal grafts were 60.0% +/- 9.07%,
      75.7% +/- 9.18%, and 93.5% +/- 6.03%, respectively, at 1 month; 53.7% +/- 11.85%,
      68.9% +/- 12.47%, and 85. 0% +/- 9.92% at 1 year; and 46.7% +/- 18.19%, 68.9% +/-
      20.54%, and 53.1% +/- 17.15% at 5 years. For infrapopliteal grafts, the
      corresponding estimates were 72.4% +/- 7.06%, 72.9% +/- 6.99%, and 92.7% +/-
      4.79% at 1 month; 55.6% +/- 10.70%, 55.4% +/- 10.07%, and 77.9% +/- 9.02% at 1
      year; and 33.6% +/- 22.36%, 55.4% +/- 30.20%, and 20.8% +/- 9.89% at 5 years.
      CONCLUSION: The composite artery-vein bypass graft is a useful autogenous
      alternative for infrainguinal arterial reconstruction when a vein of the required
      quality is not available or when the procedure needs to be confined to the
      affected limb.

PMID- 10069906
TI  - Surgical transluminal iliac angioplasty with selective stenting: long-term
      results assessed by means of duplex scanning.
AB  - PURPOSE: The safety of iliac angioplasty and selective stenting performed in the
      operating room by vascular surgeons was evaluated, and the short- and long-term
      results were assessed by means of serial duplex scanning. METHODS: Between 1989
      and 1996, 281 iliac stenotic or occlusive lesions in 235 consecutive patients
      with chronic limb ischemia were treated by means of percutaneous transluminal
      angioplasty (PTA) alone (n = 214) or PTA with stent (n = 67, 23.8%). There were
      260 primary lesions and 21 restenosis after a first PTA, which were analyzed
      separately. Stents were implanted in selected cases, either primarily in totally
      occluded arteries or after suboptimum results of PTA (ie, residual stenosis or a
      dissection). Data were collected prospectively and analyzed retrospectively.
      Results were reported in an intention-to-treat basis. Clinical results and
      patency were evaluated by means of symptom assessment, ankle brachial pressure
      index, and duplex scanning at discharge and 1, 3, 6, and every 12 months after
      angioplasty. To identify factors that may affect outcome, 12 clinical and
      radiological variables, including the four categories of lesions defined by the
      Standards of Practice Committee of the Society of Cardiovascular and
      Interventional Radiology, were analyzed separately. The statistical significances
      of life-table analysis of patency were determined by means of the log-rank test.
      RESULTS: There were no postoperative deaths or amputations. Local, general, and
      vascular complications occurred in 2.1%, 1.3% and 4.7% of cases, respectively
      (total, 8.1%). The mean follow-up period was 29.6 months. The cumulative patency
      rates +/- SE of the 260 PTAs (including 55 PTAs plus stents) were 92.9% +/- 1.5%
      at 1 month, 86. 5% +/- 1.7% at 1 year, 81.2% +/- 2.3% at 2 years, 78.8% +/- 2.9%
      at 3 years, and 75.4% +/- 3.5% at 5 and 6 years. The two-year patency rate of 21
      redo PTAs (including 11 PTAs plus stents) was 79.1% +/- 18.2%. Of 12 predictable
      variables studied in the first PTA group, only the category of the lesion was
      predictive of long-term patency. The two-year patency rate was 84% +/- 3% for 199
      category 1 lesions and 69.7% +/- 6.5% for 61 category 2, 3, and 4 lesions
      together (P =. 02). There was no difference of patency in the stented and
      nonstented group. CONCLUSION: Iliac PTA alone or with the use of a stent (in
      cases of occlusion and/or suboptimal results of PTA) offers an excellent long
      term patency rate. Categorization of lesions remains useful in predicting long
      term outcome. PTA can be performed safely by vascular surgeons in the operating
      room and should be considered to be the primary treatment for localized iliac
      occlusive disease.

PMID- 10069907
TI  - Plaque area increase and vascular remodeling contribute to lumen area change
      after percutaneous transluminal angioplasty of the femoropopliteal artery: an
      intravascular ultrasound study.
AB  - OBJECTIVE: The aim of the study was to assess the change in lumen area (LA),
      plaque area (PLA), and vessel area (VA) after percutaneous transluminal
      angioplasty (PTA) of the femoropopliteal artery. METHODS: This was a prospective
      study. Twenty patients were studied with intravascular ultrasound (IVUS)
      immediately after PTA and at follow-up examination. Multiple corresponding IVUS
      cross-sections were analyzed at the segments that were dilated by PTA (ie,
      treated sites; n = 168), including the most stenotic site (n = 20) and the
      nondilated segments (ie, reference sites; n = 77). RESULTS: At follow-up
      examination, both the PLA increase (13%) and the VA decrease (9%) resulted in a
      significant LA decrease (43%) at the most stenotic sites (P =.001). At the
      treated sites, the LA decrease (15%) was smaller and was caused by the PLA
      increase (15%). At the reference sites, the PLA increase (15%) and the VA
      increase (6%) resulted in a slight LA decrease (3%). An analysis of the IVUS
      cross-sections that were grouped according to LA change (difference >/=10%)
      revealed a similar PLA increase in all the groups: the type of vascular
      remodeling (VA decrease, no change, or increase) determined the LA change. At the
      treated sites, the LA change and the VA change correlated closely (r = 0.77, P
      <.001). At the treated sites, significantly more PLA increase was seen in the
      IVUS cross-sections that showed hard lesion or media rupture (P <.05). No
      relationship was found between the presence of dissection and the quantitative
      changes. CONCLUSION: At the most stenotic sites, lumen narrowing was caused by
      plaque increase and vessel shrinkage. Both the treated sites and the reference
      sites showed a significant PLA increase: the type of vascular remodeling
      determined the LA change at follow-up examination. The extent of the PLA increase
      was significantly larger in the IVUS cross-sections that showed hard lesion or
      media rupture.

PMID- 10069908
TI  - The value of late computed tomographic scanning in identification of vascular
      abnormalities after abdominal aortic aneurysm repair.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of late
      arterial abnormalities after aortic aneurysm repair and thus to suggest a routine
      for postoperative radiologic follow-up examination and to establish reference
      criteria for endovascular repair. METHODS: Computed tomographic (CT) scan follow
      up examination was obtained at 8 to 9 years after abdominal aortic aneurysm (AAA)
      repair on a cohort of patients enrolled in the Canadian Aneurysm Study. The
      original registry consisted of 680 patients who underwent repair of nonruptured
      AAA. When the request for CT scan follow-up examination was sent in 1994, 251
      patients were alive and potentially available for CT scan follow-up examination
      and 94 patients agreed to undergo abdominal and thoracic CT scanning procedures.
      Each scan was interpreted independently by two vascular radiologists. RESULTS:
      For analysis, the aorta was divided into five defined segments and an aneurysm
      was defined as a more than 50% enlargement from the expected normal value as
      defined in the reporting standards for aneurysms. With this strict definition,
      64.9% of patients had aneurysmal dilatation and the abnormality was considered as
      a possible indication for surgical repair in 13.8%. Of the 39 patients who
      underwent initial repair with a tube graft, 12 (30.8%) were found to have an
      iliac aneurysm and six of these aneurysms (15.4%) were of possible surgical
      significance. Graft dilatation was observed from the time of operation (median
      graft size of 18 mm) to a median size of 22 mm as measured by means of CT
      scanning at follow-up examination. Fluid or thrombus was seen around the graft in
      28% of the cases, and bowel was believed to be intimately associated with the
      graft in 7%. CONCLUSION: Late follow-up CT scans after AAA repair often show
      vascular abnormalities. Most of these abnormalities are not clinically
      significant, but, in 13.8% of patients, the thoracic or abdominal aortic segment
      was aneurysmal and, in 15.4% of patients who underwent tube graft placement, one
      of the iliac arteries was significantly abnormal to warrant consideration for
      surgical repair. On the basis of these findings, a routine CT follow-up
      examination after 5 years is recommended. This study provides a population-based
      study for comparison with the results of endovascular repair.

PMID- 10069909
TI  - Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's
      disease (endarteritis obliterans).
AB  - PURPOSE: The diagnosis of Buerger's disease has depended on clinical symptoms and
      angiographic findings, whereas pathologic findings are considered to be of
      secondary importance. Arteries from patients with Buerger's tissue were analyzed
      histologically, including immunophenotyping of the infiltrating cells, to
      elucidate the nature of Buerger's disease as a vasculitis. METHODS: Thirty-three
      specimens from nine patients, in whom Buerger's disease was diagnosed on the
      basis of our clinical and angiographic criteria between 1980 and 1995 at Nagoya
      University Hospital, were studied. Immunohistochemical studies were performed on
      paraffin-embedded tissue with a labeled streptoavidin-biotin method. RESULTS: The
      general architecture of vessel walls was well preserved regardless of the stage
      of disease, and cell infiltration was observed mainly in the thrombus and the
      intima. Among infiltrating cells, CD3(+) T cells greatly outnumbered CD20(+) B
      cells. CD68(+) macrophages or S-100(+) dendritic cells were detected, especially
      in the intima during acute and subacute stages. All cases except one showed
      infiltration by the human leukocyte antigen-D region (HLA-DR) antigen-bearing
      macrophages and dendritic cells in the intima. Immunoglobulins G, A, and M (IgG,
      IgA, IgM) and complement factors 3d and 4c (C3d, C4c) were deposited along the
      internal elastic lamina. CONCLUSION: Buerger's disease is strictly an
      endarteritis that is introduced by T-cell mediated cellular immunity and by B
      cell mediated humoral immunity associated with activation of macrophages or
      dendritic cells in the intima.

PMID- 10069910
TI  - Carotid endarterectomy and intracranial thrombolysis: simultaneous and staged
      procedures in ischemic stroke.
AB  - PURPOSE: The feasibility and safety of combining carotid surgery and thrombolysis
      for occlusions of the internal carotid artery (ICA) and the middle cerebral
      artery (MCA), either as a simultaneous or as a staged procedure in acute ischemic
      strokes, was studied. METHODS: A nonrandomized clinical pilot study, which
      included patients who had severe hemispheric carotid-related ischemic strokes and
      acute occlusions of the MCA, was performed between January 1994 and January 1998.
      Exclusion criteria were cerebral coma and major infarction established by means
      of cerebral computed tomography scan. Clinical outcome was assessed with the
      modified Rankin scale. RESULTS: Carotid reconstruction and thrombolysis was
      performed in 14 of 845 patients (1.7%). The ICA was occluded in 11 patients;
      occlusions of the MCA (mainstem/major branches/distal branch) or the anterior
      cerebral artery (ACA) were found in 14 patients. In three of the 14 patients,
      thrombolysis was performed first, followed by carotid enarterectomy (CEA) after
      clinical improvement (6 to 21 days). In 11 of 14 patients, 0.15 to 1 mIU
      urokinase was administered intraoperatively, ie, emergency CEA for acute ischemic
      stroke (n = 5) or surgical reexploration after elective CEA complicated by
      perioperative intracerebral embolism (n = 6). Thirteen of 14 intracranial embolic
      occlusions and 10 of 11 ICA occlusions were recanalized successfully (confirmed
      with angiography or transcranial Doppler studies). Four patients recovered
      completely (Rankin 0), six patients sustained a minor stroke (Rankin 2/3), two
      patients had a major stroke (Rankin 4/5), and two patients died. In one patient,
      hemorrhagic transformation of an ischemic infarction was detectable
      postoperatively. CONCLUSION: Combining carotid surgery with thrombolysis
      (simultaneous or staged procedure) offers a new therapeutic approach in the
      emergency management of an acute carotid-related stroke. Its efficacy should be
      evaluated in interdisciplinary studies.

PMID- 10069911
TI  - Right atrial bypass grafting for central venous obstruction associated with
      dialysis access: another treatment option.
AB  - PURPOSE: Central venous obstruction is a common problem in patients with chronic
      renal failure who undergo maintenance hemodialysis. We studied the use of right
      atrial bypass grafting in nine cases of central venous obstruction associated
      with upper extremity venous hypertension. To better understand the options for
      managing this condition, we discuss the roles of surgery and percutaneous
      transluminal angioplasty with stent placement. METHODS: All patients had
      previously undergone placement of bilateral temporary subclavian vein dialysis
      catheters. Severe arm swelling, graft thrombosis, or graft malfunction developed
      because of central venous stenosis or obstruction in the absence of alternative
      access sites. A large-diameter (10 to 16 mm) externally reinforced
      polytetrafluoroethylene (GoreTex) graft was used to bypass the obstructed vein
      and was anastomosed to the right atrial appendage. This technique was used to
      bypass six lesions in the subclavian vein, two lesions at the innominate
      vein/superior vena caval junction, and one lesion in the distal axillary vein.
      RESULTS: All patients except one had significant resolution of symptoms without
      operative mortality. Bypass grafts remained patent, allowing the arteriovenous
      grafts to provide functional access for 1.5 to 52 months (mean, 15.4 months)
      after surgery. CONCLUSION: Because no mortality directly resulted from the
      procedure and the morbidity rate was acceptable, this bypass grafting technique
      was adequate in maintaining the dialysis access needed by these patients. Because
      of the magnitude of the procedure, we recommend it only for the occasional
      patient in whom all other access sites are exhausted and in whom percutaneous
      dilation and/or stenting has failed.

PMID- 10069912
TI  - Evaluation of lidocaine as an analgesic when added to hypertonic saline for
      sclerotherapy.
AB  - PURPOSE: The efficacy of sclerosing agents for the treatment of telangiectasias
      and reticular veins is well established. The injection of these agents is often
      associated with pain, and it is not uncommon for sclerotherapists to include
      lidocaine with the sclerosants in an attempt to reduce the pain associated with
      treatment. However, there are concerns that this may reduce the overall efficacy
      of the treatment because of dilution of the sclerosant. Patient comfort and
      overall outcome associated with treatment using HS with lidocaine (LIDO) versus
      that using HS alone was compared. METHODS: Forty-two patients were prospectively
      entered into the study and randomized blindly to sclerotherapy with 23.4% HS or
      19% LIDO. Study subjects and treating physicians were blinded to the injection
      solution used. Injection sites were chosen for veins ranging in size from 0.1 to
      3 mm. Photographs of the area to be treated were taken, and the patients rated
      their pain. They were then observed at regular intervals for four months, and
      clinical data was collected. Thirty-five subjects completed the full follow-up
      period, and photographs of the injected area were taken again. Three
      investigators blinded to the treatment assignment then evaluated the photographs
      and scored the treatment efficacy according to a standardized system. RESULTS: In
      the HS group, 61.9% (13 of 21) patients rated their pain as none or mild, whereas
      90.5% (19 of 21) of patients in the LIDO group had no or mild discomfort. This
      difference is significant, with a P value of.034. There was no difference in the
      overall efficacy of treatment between the two groups. The groups had similar
      rates of vein thrombosis and skin necrosis. CONCLUSION: Although lidocaine is
      often used with sclerosing agents, there are no previous reports in the
      literature to evaluate its effectiveness in reducing the pain experienced by the
      patient. In this study, patients receiving LIDO experienced significantly less
      discomfort at the time of injection than patients who received HS alone. There
      were no differences in the effectiveness of treatment or in the incidence of
      complications between the two groups.

PMID- 10069913
TI  - Relief of obstructive pelvic venous symptoms with endoluminal stenting.
AB  - PURPOSE: To select patients for percutaneous transluminal stenting of chronic
      postthrombotic pelvic venous obstructions (CPPVO), we evaluated the clinical
      symptoms in a cohort of candidates and in a series of successfully treated
      patients. METHODS: The symptoms of 42 patients (39 women) with CPPVO (38 left
      iliac; average history, 18 years) were recorded, and the venous anatomy was
      studied by means of duplex scanning, subtraction venography, and computed
      tomography or magnetic resonance imaging. Successfully stented patients were
      controlled by means of duplex scanning and assessment of symptoms. RESULTS: The
      typical symptoms of CPPVO were reported spontaneously by 24% of patients and
      uncovered by means of a targeted interview in an additional 47%. Of 42 patients,
      15 had venous claudication, four had neurogenic claudication (caused by dilated
      veins in the spinal canal that arise from the collateral circulation), and 11 had
      both symptoms. Twelve patients had no specific symptoms. Placement of a stent was
      found to be technically feasible in 25 patients (60%), was attempted in 14
      patients, and was primarily successful in 12 patients. One stent occluded within
      the first week. All other stents were fully patent after a mean of 15 months
      (range, 1 to 43 months). Satisfaction was high in the patients who had the
      typical symptoms, but low in those who lacked them. CONCLUSION: Venous
      claudication and neurogenic claudication caused by venous collaterals in the
      spinal canal are typical clinical features of CPPVO. We recommend searching for
      these symptoms, because recanalization by means of stenting is often feasible and
      rewarding.

PMID- 10069914
TI  - Mid-term results of endoscopic perforator vein interruption for chronic venous
      insufficiency: lessons learned from the North American subfascial endoscopic
      perforator surgery registry. The North American Study Group.
AB  - PURPOSE: The safety, feasibility, and early efficacy of subfascial endoscopic
      perforator surgery (SEPS) for the treatment of chronic venous insufficiency were
      established in a preliminary report. The long-term clinical outcome and the late
      complications after SEPS are as yet undetermined. METHODS: The North American
      Subfascial Endoscopic Perforator Surgery registry collected information on 148
      SEPS procedures that were performed in 17 centers in the United States and Canada
      between August 1, 1993, and February 15, 1996. The data analysis in this study
      focused on mid-term outcome in 146 patients. RESULTS: One hundred forty-six
      patients (79 men and 67 women; mean age, 56 years; range, 27 to 87 years)
      underwent SEPS. One hundred and one patients (69%) had active ulcers (class 6),
      and 21 (14%) had healed ulcers (class 5). One hundred and three patients (71%)
      underwent concomitant venous procedures (stripping, 70; high ligation, 17;
      varicosity avulsion alone, 16). There were no deaths or pulmonary embolisms. One
      deep venous thrombosis occurred at 2 months. The follow-up periods averaged 24
      months (range, 1 to 53 months). Cumulative ulcer healing at 1 year was 88%
      (median time to healing, 54 days). Concomitant ablation of superficial reflux and
      lack of deep venous obstruction predicted ulcer healing (P <.05). Clinical score
      improved from 8.93 to 3.98 at the last follow-up (P <. 0001). Cumulative ulcer
      recurrence at 1 year was 16% and at 2 years was 28% (standard error, < 10%). Post
      thrombotic limbs had a higher 2-year cumulative recurrence rate (46%) than did
      those limbs with primary valvular incompetence (20%; P <.05). Twenty-eight of the
      122 patients (23%) who had class 5 or class 6 ulcers before surgery had an active
      ulcer at the last follow-up examination. CONCLUSIONS: The interruption of
      perforators with ablation of superficial reflux is effective in decreasing the
      symptoms of chronic venous insufficiency and rapidly healing ulcers. Recurrence
      or new ulcer development, however, is still significant, particularly in post
      thrombotic limbs. The reevaluation of the indications for SEPS is warranted
      because operations in patients without previous deep vein thrombosis are
      successful but operations in those patients with deep vein thrombosis are less
      successful. Operations on patients with deep vein occlusion have poor outcomes.

PMID- 10069915
TI  - The diameter of the common femoral artery in healthy human: influence of sex,
      age, and body size.
AB  - PURPOSE: To determine the relevance of dilatations of the common femoral artery
      (CFA), knowledge of the normal CFA diameter is essential. The diameter of the CFA
      in healthy male and female subjects of different ages was investigated. METHODS:
      The diameter of the CFA was measured in 122 healthy volunteers (59 male, 63
      female; 8 to 81 years of age) with echo-tracking B-mode ultrasound scan. The
      influence of age, sex, height, weight, body surface area (BSA), and systolic
      blood pressure was analyzed by means of a multiple regression model. RESULTS: The
      CFA increased steadily in diameter throughout life. From 25 years onwards, the
      diameter was larger in men than in women. Significant correlations were found
      between the CFA diameter and weight (r = 0.58 and r = 0.57 in male and female
      subjects, respectively; P <.0001), height (r = 0.49 and r = 0.54 in male and
      female subjects, respectively; P <.0001), and BSA (r = 0.60 and r = 0.62 in male
      and female subjects, respectively; P <.0001). Age and BSA were used to create a
      model for prediction of the CFA diameter (r = 0.71 and r = 0.77 in male and
      female subjects, respectively; P <.0001). CONCLUSION: The diameter of the CFA
      increases with age, initially during growth but also in adults. This is related
      to age, body size, and sex male subjects have larger arteries than female
      subjects. It is now possible to predict the normal CFA diameter, and nomograms
      that may be used in the study of aneurysmal disease are presented.

PMID- 10069916
TI  - The effect of mannitol versus dimethyl thiourea at attenuating
      ischemia/reperfusion-induced injury to skeletal muscle.
AB  - OBJECTIVE: Mannitol is used as a treatment for skeletal muscle
      ischemia/reperfusion (I/R) injury in humans, despite the fact that its
      effectiveness in vivo is still disputed. The purpose of this study was to
      determine the efficacy of mannitol in attenuating I/R injury at the
      microcirculatory level. METHODS: The study was designed as an experimental study
      with male Wistar rats. The main outcome measures were intravital microscopy,
      which was used to measure capillary perfusion, capillary and venular red blood
      cell velocity (VRBC), and leukocyte-endothelial interactions in the extensor
      digitorum longus muscle of the rat hind limb before and after ischemia. In
      addition, tissue injury was assessed during reperfusion with the fluorescent
      vital dyes bisbenzimide and ethidium bromide. Dimethyl thiourea (DMTU), a highly
      effective therapeutic agent of experimental I/R injury, was used as a positive
      control. RESULTS: No-flow ischemia (2 hour) resulted in a 40% drop in capillary
      perfusion, a decline in capillary and venular VRBC, and increased leukocyte
      venular adherence and tissue infiltration. Tissue injury increased to a constant
      level during reperfusion. Mannitol attenuated capillary malperfusion during the
      first 60 minutes of reperfusion and prevented a decline in capillary VRBC.
      However, mannitol did not reduce tissue injury or leukocyte adherence and
      infiltration during reperfusion. By comparison, DMTU not only prevented the
      perfusion deficits and the increases in leukocyte venular adherence and tissue
      infiltration but significantly reduced the magnitude of tissue injury.
      CONCLUSION: Our findings suggest that mannitol may be of limited value for the
      prevention of early reperfusion-induced injury after no-flow ischemia in skeletal
      muscle. By comparison, DMTU was highly efficacious by not only reducing
      microvascular perfusion deficits but by also reducing leukocyte-endothelial cell
      interactions and the incidence of cellular injury.

PMID- 10069917
TI  - Suppression of experimental abdominal aortic aneurysms by systemic treatment with
      a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908).
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with chronic
      inflammation, disruption of medial elastin, and increased local production of
      elastolytic matrix metalloproteinases (MMPs). The purpose of this study was to
      investigate how treatment with a hydroxamate-based MMP antagonist (RS 132908)
      might affect the development of experimental AAAs. METHODS: Male Wistar rats
      underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine
      pancreatic elastase followed by treatment for 14 days with RS 132908 (100
      mg/kg/day subcutaneously; n = 8) or with vehicle alone (n = 6). The external
      aortic diameter (AD) was measured in millimeters before elastase perfusion and at
      death, with AAA defined as an increase in AD (DeltaAD) of at least 100%. Aortic
      wall elastin and collagen concentrations were measured with assays for desmosine
      and hydroxyproline, and fixed aortic tissues were examined by light microscopy.
      RESULTS: AAAs developed in all vehicle-treated rats, with a mean AD (+/- SE) that
      increased from 1.60 +/- 0.03 mm before perfusion to 5.98 +/- 1.02 mm on day 14
      (DeltaAD = 276.4 +/- 67.7%). AAAs developed in only five of eight animals (62.5%)
      after MMP inhibition, with a mean AD that increased from 1.56 +/- 0.05 mm to 3.59
      +/- 0.34 mm (DeltaAD = 128.1 +/- 18.7%; P <.05, vs vehicle). The overall
      inhibition of aortic dilatation attributable to RS 132908 was 53.6 +/- 6.8%.
      Aortic wall desmosine fell by 85.4% in the vehicle-treated rats (1210.6 +/- 87.8
      pmol/sample to 176.7 +/- 33.4 pmol/sample; P <.05) but only by 65.6% in the
      animals treated with RS 312908 (416.2 +/- 120.5 pmol/sample). In contrast,
      hydroxyproline was not significantly affected by either elastase perfusion or
      drug treatment. Microscopic examination revealed the preservation of pericellular
      elastin and a greater degree of fibrocollagenous wall thickening after MMP
      inhibition, with no detectable difference in the extent of inflammation.
      CONCLUSIONS: Systemic MMP inhibition suppresses aneurysmal dilatation in the
      elastase-induced rodent model of AAA. Consistent with its direct inhibitory
      effect on various MMPs, RS 132908 promotes the preservation of aortic elastin and
      appears to enhance a profibrotic response within the aortic wall. Hydroxamate
      based MMP antagonists may therefore be useful in the development of pharmacologic
      approaches to the suppression of AAAs.

PMID- 10069918
TI  - Use of high-intensity focused ultrasound to control bleeding.
AB  - OBJECTIVE: High-intensity focused ultrasound (HIFU) has been shown to be
      effective in controlling hemorrhage from punctures in blood vessels. The
      objective of the current study was to investigate the capability of HIFU to stop
      bleeding after a more severe type of vascular injury, namely longitudinal
      incisions of arteries and veins. METHODS: The superficial femoral arteries,
      common femoral arteries, carotid arteries, and jugular veins of four anesthetized
      pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was
      produced in the vessel. HIFU treatment was applied within 5 seconds of the onset
      of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric
      transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm
      in axial dimension. The entire incision area was scanned with the HIFU beam at a
      rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of
      76 incisions and HIFU treatments were performed. RESULTS: Control of bleeding
      (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis
      achieved in 69 treatments (91%). The average treatment times of major and
      complete hemostasis were 17 and 25 seconds, respectively. After the treatment,
      74% of the vessels in which complete hemostasis was achieved were patent with
      distal blood flow and 26% were occluded. The HIFU-treated vessels showed a
      consistent coagulation of the adventitia surrounding the vessels, with a
      remarkably localized injury to the vessel wall. Extensive fibrin deposition at
      the treatment site was observed. CONCLUSION: HIFU may provide a useful method of
      achieving hemostasis for arteries and veins in a variety of clinical
      applications.

PMID- 10069919
TI  - Adventitial delivery minimizes the proinflammatory effects of adenoviral vectors.
AB  - PURPOSE: Adenovirus-mediated arterial gene transfer is a promising tool in the
      study of vascular biology and the development of vascular gene therapy. However,
      intraluminal delivery of adenoviral vectors causes vascular inflammation and
      neointimal formation. Whether these complications could be avoided and gene
      transfer efficiency maintained by means of delivering adenoviral vectors via the
      adventitia was studied. METHODS: Replication-defective adenoviral vectors
      encoding a beta-galactosidase (beta-gal) gene (AdRSVnLacZ) or without a
      recombinant gene (AdNull) were infused into the lumen or the adventitia of rabbit
      carotid arteries. Two days after infusion of either AdRSVnLacZ (n = 8
      adventitial, n = 8 luminal) or AdNull (n = 4 luminal), recombinant gene
      expression was quantitated by histochemistry (performed on tissue sections) and
      with a beta-gal activity assay (performed on vessel extracts). Inflammation
      caused by adenovirus infusion was assessed 14 days after infusion of either
      AdNull (n = 6) or vehicle (n = 6) into the carotid adventitia. Inflammation was
      assessed by means of examination of histologic sections for the presence of
      neointimal formation and infiltrating T cells and for the expression of markers
      of vascular cell activation (ICAM-1 and VCAM-1). To measure the systemic immune
      response to adventitial infusion of adenovirus, plasma samples (n = 3) were drawn
      14 days after infusion of AdNull and assayed for neutralizing antibodies.
      RESULTS: Two days after luminal infusion of AdRSVnLacZ, approximately 30% of
      luminal endothelial cells expressed beta-gal. Similarly, 2 days after infusion of
      AdRSVnLacZ to the adventitia, approximately 30% of adventitial cells expressed
      beta-gal. beta-gal expression was present in the carotid adventitia, the internal
      jugular vein adventitia, and the vagus nerve perineurium. Elevated beta-gal
      activity (50- to 80-fold more than background; P <.05) was detected in extracts
      made from all AdRSVnLacZ-transduced arteries. The amount of recombinant protein
      expression per vessel did not differ significantly between vessels transduced via
      the adventitia (17.1 mU/mg total protein [range, 8.1 to 71.5]) and those
      transduced via a luminal approach (10.0 mU/mg total protein [range, 3.9 to
      42.6]). Notably, adventitial delivery of AdNull did not cause neointimal
      formation. In addition, vascular inflammation in arteries transduced via the
      adventitia (ie, T-cell infiltrates and ICAM-1 expression) was confined to the
      adventitia, sparing both the intima and media. Antiadenoviral neutralizing
      antibodies were present in all rabbits after adventitial delivery of AdNull.
      CONCLUSION: Infusion of adenoviral vectors into the carotid artery adventitia
      achieves recombinant gene expression at a level equivalent to that achieved by
      means of intraluminal vector infusion. Because adventitial gene transfer can be
      performed by means of direct application during open surgical procedures, this
      technically simple procedure may be more clinically applicable than intraluminal
      delivery. Moreover, despite the generation of a systemic immune response,
      adventitial infusion had no detectable pathologic effects on the vascular intima
      or media. For these reasons, adventitial gene delivery may be a particularly
      useful experimental and clinical tool.

PMID- 10069920
TI  - Endovascular repair of a descending thoracic aortic aneurysm: a tip for systemic
      pressure reduction.
AB  - A proposed technique for systemic pressure reduction during deployment of a stent
      graft was studied. A 67-year-old man, who had a descending thoracic aneurysm, was
      successfully treated with an endovascular procedure. An occluding balloon was
      introduced into the inferior vena cava (IVC) through the femoral vein. The
      balloon volume was manipulated with carbon dioxide gas to reduce the venous
      return, resulting in a transient and well-controlled hypotension. This IVC
      occluding technique for systemic pressure reduction may be safe and convenient to
      minimize distal migration of stent grafts.

PMID- 10069921
TI  - Infrarenal endoluminal bifurcated stent graft infected with Listeria
      monocytogenes.
AB  - Prosthetic graft infection as a result of Listeria monocytogenes is an extremely
      rare event that recently occurred in a 77-year-old man who underwent endoluminal
      stent grafting for infrarenal abdominal aortic aneurysm. The infected aortic
      endoluminal prosthesis was removed by means of en bloc resection of the aneurysm
      and contained endograft with in situ aortoiliac reconstruction. At the 10-month
      follow-up examination, the patient was well and had no signs of infection.

PMID- 10069922
TI  - Endovascular stent graft repair of aortopulmonary fistula.
AB  - Two patients who had aortopulmonary fistula of postoperative origin with
      hemoptysis underwent successful repair by means of an endovascular stent graft
      procedure. One patient had undergone repeated thoracotomies two times, and the
      other one time to repair anastomotic aneurysms of the descending aorta after
      surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered
      with a Dacron graft was inserted into the lesion through the external iliac or
      femoral artery. The patients recovered well, with no signs of infection or
      recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting
      may be a therapeutic option for treating patients with aortopulmonary fistula.

PMID- 10069923
TI  - Popliteal artery occlusion as a late complication of liquid acrylate embolization
      for cerebral vascular malformation.
AB  - Occlusion of arteriovenous malformations of the brain (BAVMs) by means of an
      endovascular approach with liquid acrylate glue is an established treatment
      modality. The specific hazards of this procedure are related to the central
      nervous system. In the case of unexpectedly rapid polymerization of the
      cyanoacrylate glue and adhesion of the delivering microcatheter to the BAVM,
      severing the catheter at the site of vascular access is considered an acceptable
      and safe management. We present a unique complication related to this technique
      that has not been described yet. Fragmentation and migration of the
      microcatheter, originally left in place, had caused popliteal artery occlusion,
      which required saphenous vein interposition, in a 25-year-old man. Suggestions
      for avoiding this complication are discussed.

PMID- 10069924
TI  - The US Food and Drug Administration investigational device exemptions (IDE) and
      clinical investigation of cardiovascular devices: information for the
      investigator.
AB  - The conduct of a clinical investigation of a medical device to determine the
      safety and effectiveness of the device is covered by the investigational device
      exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to
      the extent consistent with the protection of public health and safety and with
      ethical standards, the discovery and development of useful devices intended for
      human use, and to that end to maintain optimum freedom for scientific
      investigators in their pursuit of this purpose" (Federal Food, Drug, and Cosmetic
      Act). Conducting a clinical investigation may require an approved IDE
      application. The US Food and Drug Administration encourages early interaction
      with the agency through the pre-IDE process during the development of a device or
      technology and during the preparation of an IDE application. This facilitates
      approval of the IDE application and progression into the clinical investigation.
      This paper reviews the terminology and applicability of the IDE regulation and
      the type of study that requires an IDE application to the Food and Drug
      Administration. The pre-IDE process and the development of an IDE application for
      a significant risk study of a cardiovascular device are discussed.

PMID- 10069925
TI  - Regarding "early history of aortic surgery".

PMID- 10069926
TI  - Vitamin C and endothelial dysfunction: what is new?

PMID- 10069927
TI  - Prevalence of penicillin-resistant viridans streptococci in the oral flora of
      Japanese children at risk for infective endocarditis.

PMID- 10069928
TI  - Variability of the lumped constant for [18F]2-deoxy-2-fluoroglucose and the
      experimental isolated rat heart model: clinical perspectives for the measurement
      of myocardial tissue viability in humans.

PMID- 10069929
TI  - Effect of fluticasone propionate nasal spray on the hypothalamic-pituitary
      adrenal axis.

PMID- 10069930
TI  - Reply.

PMID- 10069931
TI  - Regarding "early history of aortic surgery".

PMID- 10069932
TI  - Reply.

PMID- 10069933
TI  - "Proper" Binormal ROC Curves: Theory and Maximum-Likelihood Estimation.
AB  - The conventional binormal model, which assumes that a pair of latent normal
      decision-variable distributions underlies ROC data, has been used successfully
      for many years to fit smooth ROC curves. However, if the conventional binormal
      model is used for small data sets or ordinal-category data with poorly allocated
      category boundaries, a "hook" in the fitted ROC may be evident near the upper
      right or lower-left corner of the unit square. To overcome this curve-fitting
      artifact, we developed a "proper" binormal model and a new algorithm for maximum
      likelihood (ML) estimation of the corresponding ROC curves. Extensive simulation
      studies have shown the algorithm to be highly reliable. ML estimates of the
      proper and conventional binormal ROC curves are virtually identical when the
      conventional binormal ROC shows no "hook," but the proper binormal curves have
      monotonic slope for all data sets, including those for which the conventional
      model produces degenerate fits. Copyright 1999 Academic Press.

PMID- 10069934
TI  - A Dynamic Model of Cognitive Growth in a Population: Spatial Tasks and
      Conservation.
AB  - A dynamic model of cognitive growth is developed that is applicable to cross
      sectional studies of growth in a population, and that predicts the distribution
      of scores as a function of age. This model modifies the theory of P. van Geert
      (1991, Psychological Review, 98, 3-53) for the cognitive growth of an individual
      under limited resources, by taking into account the effect of schooling or
      training. The modified theory provides an explanation for the puzzling effect
      reported by C. J. Brainerd (1977, Psychological Bulletin, 84, 919-939), that the
      gain in scores obtained in concept training experiments is independent of the
      initial state of the learner. In developing the modified theory, it was found
      that the assumption of delayed feedback is unnecessary. To apply the model to
      populations, it was assumed that the ability parameters that appear in the growth
      function are distributed normally in the population. A distribution function G(s;
      t) was derived that predicts the distributions of scores s at age t in terms of a
      small number of parameters. Although the abilities are assumed to be distributed
      normally, the score distributions are often bimodal. The model was applied to the
      studies of H. Thomas and A. Lohaus (1993, Monographs of the Society for Research
      in Child Development, 58, 1-169) on the growth of the concepts of verticality and
      horizontality, and to the study of P. M. Bentler (1970, Perceptual and Motor
      Skills, 31, 855-859) on the growth of the concept of conservation. In these
      applications the score distributions are clearly bimodal, but there is no
      evidence of abrupt transitions or catastrophes. This shows that the presence of a
      "catastrophe flag" (bimodal distributions) does not necessarily imply the
      presence of a catastrophe. Copyright 1999 Academic Press.

PMID- 10069935
TI  - Functional Equations in Binocular Space Perception.
AB  - A general theory of the relationship of binocular visual space to physical space
      is formulated within a conjoint measurement framework. Psychophysically motivated
      invariance relations induce various functional equations. Another class of
      functional equations arises if we additionally assume the validity of a different
      psychophysical theory that is based on a formula suggested by A. A. Blank. We
      solve and interpret most of these equations and point out an unsolved problem.
      The obtained results lead to a measurement-theoretic foundation of the
      psychophysical assumptions underlying the Luneburg theory of binocular vision.
      They also contribute to clarifying the relationship between the presented general
      theory and Blank's approach. Copyright 1999 Academic Press.

PMID- 10069936
TI  - A Generic Disjunctive/Conjunctive Decomposition Model for n-ary Relations.
AB  - This paper discusses a generic decomposition model that represents an arbitrary n
      ary relation as a disjunctive or conjunctive combination of a number of n-ary
      component relations of a prespecified type. An important subclass of order
      preserving decompositions is defined and its properties are derived. The generic
      model is shown to subsume various known models as special cases, including the
      models of Boolean factor analysis, hierarchical classes analysis, and
      disjunctive/conjunctive nonmetric factor analysis. Moreover, it also subsumes a
      broad range of new models as exemplified with a novel model for multidimensional
      parallelogram analysis and novel three-way extensions of nonmetric factor
      analysis. Copyright 1999 Academic Press.

PMID- 10069937
TI  - Conditionally Selective Dependence of Random Variables on External Factors.
AB  - Selective influence of experimental factors upon observable or hypothetical
      random variables is a key concept in the analysis of processing architectures and
      response time decompositions. This paper deals with the notion of conditionally
      selective influence, defined as follows. Let {X1, em leader, Xn} be
      stochastically interdependent random variables (e.g., hypothetical components of
      response time), and let Phi be a set of external factors affecting the joint
      distribution of {X1, em leader, Xn}. A subset of factors &Lambdai conditionally
      selectively influences Xi if at any fixed values of the remaining random
      variables the conditional distribution of Xi only depends on factors inside
      &Lambdai. The notion of conditional selectivity generalizes the relationship
      between factors and random variables described in Townsend (1984) as "indirect
      nonselectivity." This paper establishes the structure of the joint distribution
      of {X1, em leader, Xn} that is necessary and sufficient for {X1, em leader, Xn}
      to be conditionally selectively influenced by (not necessarily disjoint) factor
      subsets {&Lambda1, em leader, Gamman}, respectively. The notion of conditional
      selectivity is compared to that of unconditional selectivity, defined as follows.
      A subset of factors &Gammai unconditionally selectively influences Xi if the
      latter can be presented as a deterministic function of &Gammai and of some random
      variables (the same for all Xi, i=1, em leader, n) whose joint distribution does
      not depend on any factors from Phi. The two forms of selective influence are
      generally incompatible. Copyright 1999 Academic Press.

PMID- 10069939
TI  - TELEGRAPHIC REVIEWS.

PMID- 10069940
TI  - CORRIGENDUM.

PMID- 10069941
TI  - RECENTLY ACCEPTED MANUSCRIPTS.

PMID- 10069942
TI  - Work and Family Stress and Well-Being: An Examination of Person-Environment Fit
      in the Work and Family Domains.
AB  - Research indicates that work and family are significant sources of stress.
      However, this research has underemphasized the cognitive appraisal process by
      which work and family generate stress. This study used person-environment fit
      theory to examine how the comparison of work and family experiences to the
      person's values relates to stress and well-being. Using data from 1758 employees,
      we assessed fit regarding autonomy, relationships, security, and segmentation for
      both work and family, and examined the relationship of fit with work and family
      satisfaction, anxiety, depression, irritation, and somatic symptoms. In general,
      well-being improved as experiences increased toward values and improved to a
      lesser extent as experiences exceeded values. Well-being was also higher when
      experiences and values were both high than when both were low. These
      relationships were generally strongest for within-domain fit and well-being
      (i.e., work fit and work satisfaction, family fit and family satisfaction), and
      several relationships were moderated by work and family centrality. Copyright
      1999 Academic Press.

PMID- 10069943
TI  - Effectiveness of Positive Hypothesis Testing in Inductive and Deductive Rule
      Learning.
AB  - In a positive hypothesis test a person generates or examines evidence that is
      expected to have the property of interest if the hypothesis is correct, whereas
      in a negative hypothesis test a person generates or examines evidence that is not
      expected to have the property of interest if the hypothesis is correct. Two
      experiments assessed the effectiveness of positive versus negative hypothesis
      tests on inductive and deductive rule learning problems. In Experiment 1 problem
      solvers induced a rule by proposing hypotheses and selecting evidence in the
      eight conditions of a factorial design defined by instructions to use a positive
      or negative hypothesis test on each of trials 1-5, 6-10, and 11-15. Instructions
      to use positive tests resulted in more examples, fewer strategic hypotheses, and
      a higher weighted score for five types of hypotheses than instructions to use
      negative tests. In Experiment 2 problem solvers identified 1 of a possible 1296
      correct rules in the deductive rule learning game Mastermind. When problems were
      classified in the 16 possible combinations of positive or negative hypothesis
      tests on trials 2, 3, 4, and 5 there were fewer trials to solution for positive
      tests on each of the four trials and fewer trials to solution with increasing
      positive tests. We conclude that positive hypothesis tests are generally more
      effective than negative hypothesis tests in both inductive and deductive rule
      learning. Copyright 1999 Academic Press.

PMID- 10069944
TI  - Cross-Cultural Differences in Choice Behavior and Use of Decision Aids: A
      Comparison of Japan and the United States.
AB  - A controlled laboratory study was conducted to investigate the effect of cultural
      differences on decision strategy. Participants from two cultures (Japan and the
      United States) completed multi-attribute preferential choice tasks with and
      without use of computerized decision aids. The results indicate that Japanese
      participants were less likely to invoke compensatory decision processes, which
      involve conflict-confronting assessment of trade-offs among attributes. This
      behavior is consistent with some cultural differences described in extant
      literature. The results call into question the generalizability across cultures
      of descriptive decision theories, which come largely from the West, and suggest
      the need for descriptive theories that incorporate cultural factors. Copyright
      1999 Academic Press.

PMID- 10069945
TI  - Integration of banana streak badnavirus into the Musa genome: molecular and
      cytogenetic evidence.
AB  - Breeding and tissue culture of certain cultivars of bananas (Musa) have led to
      high levels of banana streak badnavirus (BSV) infection in progeny from
      symptomless parents. BSV DNA hybridized to genomic DNA of one such parent, Obino
      l'Ewai, suggesting integration of viral sequences. Sequencing of clones of Obino
      l'Ewai genomic DNA revealed an interface between BSV and Musa sequences and a
      complex BSV integrant. In situ hybridization revealed two different BSV sequence
      locations in Obino l'Ewai chromosomes and a complex arrangement of BSV and Musa
      sequences was shown by probing stretched DNA fibers. This is the first report of
      integrated sequences that possibly lead to a plant pararetrovirus episomal
      infection by a mechanism differing markedly from animal retroviral systems.

PMID- 10069946
TI  - Evidence that badnavirus infection in Musa can originate from integrated
      pararetroviral sequences.
AB  - When some virus- and disease-free Musa spp. (banana and plantain) are propagated
      by tissue culture, the resulting plants develop infections with banana streak
      badnavirus (BSV), a pararetrovirus. In sharp contrast to the virion DNA recovered
      from natural infections, the virion DNA from tissue culture-associated infections
      of different Musa spp. was highly similar if not identical. Although BSV does not
      employ integration during the infection cycle, BSV DNA was found to be integrated
      into the Musa genome. While one integration consisted of a partial BSV genome, a
      second contained more than one complete genome that was almost identical to BSV
      recovered from tissue culture-derived plants. The arrangement of this integrated
      BSV DNA suggests that it can yield an infectious episomal genome via homologous
      recombination. This report documents the first instance of integrated DNA of a
      nonintegrating virus giving rise to an episomal viral infection and identifies
      tissue culture as a possible trigger for the infection, raising the question of
      whether similar activatable viral sequences exist in the genomes of other plants
      and animals.

PMID- 10069947
TI  - Poliomyelitis in intraspinally inoculated poliovirus receptor transgenic mice.
AB  - Mice transgenic with the human poliovirus receptor gene develop clinical signs
      and neuropathology similar to those of human poliomyelitis when neurovirulent
      polioviruses are inoculated into the central nervous system (CNS). Factors
      contributing to disease severity and the frequencies of paralysis and mortality
      include the poliovirus strain, dose, and gender of the mouse inoculated. The more
      neurovirulent the virus, as defined by monkey challenge results, the higher the
      rate of paralysis, mortality, and severity of disease. Also, the time to disease
      onset is shorter for more neurovirulent viruses. Male mice are more susceptible
      to polioviruses than females. TGM-PRG-3 mice have a 10-fold higher transgene copy
      number and produce 3-fold more receptor RNA and protein levels in the CNS than
      TGM-PRG-1 mice. CNS inoculations with type III polioviruses differing in relative
      neurovirulence show that these mouse lines are similar in disease frequency and
      severity, demonstrating that differences in receptor gene dosage and concomitant
      receptor abundance do not affect susceptibility to infection. However, there is a
      difference in the rate of accumulation of clinical signs. The time to onset of
      disease is shorter for TGM-PRG-3 than TGM-PRG-1 mice. Thus, receptor dosage
      affects the rate of appearance of poliomyelitis in these mice.

PMID- 10069948
TI  - Specific binding of recombinant foamy virus envelope protein to host cells
      correlates with susceptibility to infection.
AB  - The interaction of simian foamy viruses (FVs) with their putative cellular
      receptor(s) was studied with two types of recombinant envelope protein (Env).
      Transient expression of full-length Env in BHK-21 cells induced syncytia
      formation. However, selected stable transfectants fused with naive cells but not
      with each other. A soluble fusion protein of the Env surface domain with the Fc
      fragment of a human IgG1 heavy chain (EnvSU-Ig) was produced in the baculovirus
      expression system, purified to homogeneity, and used for binding and competition
      analyses. EnvSU-Ig but not unrelated Ig fusion proteins bound to cells
      specifically. Neutralizing serum blocked binding of EnvSU-Ig and, vice versa,
      serum-mediated neutralization was abrogated by the chimeric protein. Concomitant
      reduction of EnvSU-Ig binding and FV susceptibility was seen in Env-expressing
      target cells. Although EnvSU-Ig did not inhibit FV infection, very likely due to
      its displacement by multivalent virus-cell interactions, this divalent ligand
      should help to characterize functionally and to identify the ubiquitous FV
      receptor.

PMID- 10069949
TI  - Effect of rev on the cytoplasmic localization of intron-containing human
      immunodeficiency virus type 1 RNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) proteins are expressed from both
      intron-containing and completely spliced RNAs. Rev, an HIV-1 regulatory protein,
      is necessary for the expression of intron-containing RNAs. The effect of Rev on
      the subcellular localization of intron-containing HIV-1 RNA was examined by in
      situ RNA hybridization. In the presence of Rev, intron-containing HIV-1 RNA
      accumulated at the nuclear membrane and within the cytoplasm of transfected
      cells. In the absence of Rev, intron-containing HIV-1 RNA accumulated within the
      nucleus. In approximately 20% of the cells transfected in the absence of Rev,
      intron-containing HIV-1 RNA was also found in the cytoplasm. Differences in the
      subcytoplasmic localization of intron-containing HIV-1 RNA in the presence and
      absence of Rev were not observed using in situ RNA hybridization. To determine
      the effect of Rev on RNA localization within the cytoplasm, an extensive
      fractionation protocol involving both hypotonic and detergent lysis was used. In
      the presence of Rev, 40.9 +/- 4.6% of the cytoplasmic intron-containing HIV-1 RNA
      was released by hypotonic lysis. A similar fractionation profile was seen for
      several other translated viral and cellular RNAs. However, in the absence of Rev,
      only 16.5 +/- 5.1% of the cytoplasmic intron-containing HIV-1 RNA was released on
      hypotonic lysis (P < 0. 005). Thus the cytoplasmic fractionation pattern of this
      RNA was altered in the absence of Rev.

PMID- 10069950
TI  - Sequence heterogeneity within three different regions of the hepatitis G virus
      genome.
AB  - Two sets of primers derived from the 5'-terminal region and the NS5 region of the
      hepatitis G virus (HGV) genome were used to amplify PCR fragments from serum
      specimens obtained from different parts of the world. All PCR fragments from the
      5'-terminal region (5'-PCR, n = 56) and from the NS5 region (NS5-PCR, n = 85)
      were sequenced and compared to corresponding published HGV sequences. The range
      of nucleotide sequence similarity varied from 74 and 78% to 100% for 5'-PCR and
      NS5-PCR fragments, respectively. Additionally, five overlapping PCR fragments
      comprising an approximately 2.0-kb structural region of the HGV genome were
      sequenced from each of five sera obtained from three United States residents.
      These sequences were compared to 20 published sequences comprising the same
      region of the HGV genome. Nucleotide and deduced amino acid sequences obtained
      from different individuals were homologous from 82.9 to 93. 6% and from 90.4 to
      99.0%, respectively. Sequences obtained from follow-up specimens were almost
      identical. Comparative analysis of deduced amino acid sequences of the HGV
      structural proteins and hepatitis C virus (HCV) structural proteins combined with
      an analysis of predicted secondary structures and hydrophobic profiles allowed
      prediction of processing sites within the HGV structural proteins. A phylogenetic
      sequence analysis performed on the 2.0-kb structural region supports the
      existence of three previously identified HGV genetic groups. However,
      phylogenetic analysis performed on only small DNA fragments yielded inconsistent
      genetic grouping and failed to confirm the existence of genetic groups. Thus, in
      contrast to HCV where almost any region can be used for genotyping, only large or
      carefully selected genome fragments can be used to identify consistent HGV
      genetic groups.

PMID- 10069951
TI  - Flexibility of the major antigenic loop of foot-and-mouth disease virus bound to
      a Fab fragment of a neutralising antibody: structure and neutralisation.
AB  - The interaction of foot-and-mouth disease virus (FMDV) serotype C (clone C-S8c1)
      with a strongly neutralising monoclonal antibody (MAb) 4C4 has been studied by
      combining data from cryoelectron microscopy and x-ray crystallography. The MAb
      4C4 binds to the exposed flexible GH-loop of viral protein 1 (VP1), which appears
      to retain its flexibility, allowing movement of the bound Fab. This is in
      striking contrast to MAb SD6, which binds to the same GH-loop of VP1 but exhibits
      no movement of the bound Fab when observed under identical conditions. However,
      MAbs 4C4 and SD6 have very similar neutralisation characteristics. The known
      atomic structure of FMDV C-S8c1 and that of the 4C4 Fab cocrystallised with a
      synthetic peptide corresponding to the GH-loop of VP1 were fitted to the
      cryoelectron microscope density map. The best fit of the 4C4 Fab is compatible
      only with monovalent binding of the MAb in agreement with the neutralisation data
      on 4C4 MAbs, Fab2s, and Fabs. The position of the bound GH-loop is related to
      other known positions of this loop by a hinge rotation about the base of the
      loop. The 4C4 Fab appears to interact almost exclusively with the G-H loop of
      VP1, making no other contacts with the viral capsid.

PMID- 10069952
TI  - DNA vaccination with hantavirus M segment elicits neutralizing antibodies and
      protects against seoul virus infection.
AB  - Seoul virus (SEOV) is one of four known hantaviruses causing hemorrhagic fever
      with renal syndrome (HFRS). Candidate naked DNA vaccines for HFRS were
      constructed by subcloning cDNA representing the medium (M; encoding the G1 and G2
      glycoproteins) or small (S; encoding the nucleocapsid protein) genome segment of
      SEOV into the DNA expression vector pWRG7077. We vaccinated BALB/c mice with
      three doses of the M or S DNA vaccine at 4-week intervals by either gene gun
      inoculation of the epidermis or needle inoculation into the gastrocnemius muscle.
      Both routes of vaccination resulted in antibody responses as measured by ELISA;
      however, gene gun inoculation elicited a higher frequency of seroconversion and
      higher levels of antibodies in individual mice. We vaccinated Syrian hamsters
      with the M or S construct using the gene gun and found hantavirus-specific
      antibodies in five of five and four of five hamsters, respectively. Animals
      vaccinated with the M construct developed a neutralizing antibody response that
      was greatly enhanced in the presence of guinea pig complement. Immunized hamsters
      were challenged with SEOV and, after 28 days, were monitored for evidence of
      infection. Hamsters vaccinated with M were protected from infection, but hamsters
      vaccinated with S were not protected.

PMID- 10069953
TI  - Two types of HTLV-1 particles are released from MT-2 cells.
AB  - The MT-2 cell line transformed by human T-cell leukemia virus type 1 (HTLV-1)
      contains one complete provirus and seven defective proviruses. Four defective
      genomes have an identical structure (LTR-MA-deltaCA-pX-LTR) with an open reading
      frame that spans from MA to pX, giving rise to a 3.4-kb (24S) RNA transcript
      encoding a chimeric Gag-pX protein, p28. MT-2 cells release two distinct types of
      virions. The major "classic" type of particle has a buoyant density of 1.155-1.16
      g/cm3 and contains the standard HTLV-I structural proteins and reverse
      transcriptase (RT). In addition, about 5% of particles are "light," approximately
      1.12 g/cm3, and contain p28, RT activity, and the 3.4-kb RNA transcript. RT-PCR
      and in vitro translation indicate that some of the classic HTLV-1 particles
      package 3.4-kb RNA as well as full-length 8.5-kb RNA. In addition to matrix
      features, the p28 protein has a motif resembling a zinc finger at the C-terminal,
      pX0 region, which may play a role in the assembly of the defective light virions.

PMID- 10069954
TI  - RANTES, IFN-gamma, CCR1, and CCR5 mRNA expression in peripheral blood, lymph
      node, and bronchoalveolar lavage mononuclear cells during primary simian
      immunodeficiency virus infection of macaques.
AB  - Primary infection of macaques with pathogenic isolates of simian immunodeficiency
      virus (SIV) (as a model of HIV infection in humans) represents a unique
      opportunity to study early lentivirus/host interactions. We sought to determine
      whether there is a temporal relationship linking SIV replication and
      dissemination and the expression of the chemokine RANTES (regulated upon
      activation normal T cell expressed and secreted) and the SIV/HIV coreceptor CCR5
      in different tissues during acute SIV infection of macaques. Four cynomolgus
      macaques were inoculated intravenously with a pathogenic primary isolate of
      SIVmac251. RT-PCR was used to monitor the expression of RANTES and CCR5 mRNA in
      fresh isolated mononuclear cells from blood, lymph node, and bronchoalveolar
      lavages. These expressions were compared to those of IFN-gamma as an indicator of
      the development of the immune response and to another receptor for RANTES, CCR1,
      which is not described as a coreceptor for SIV/HIV-1 entry. An enhancement of
      CCR1/CCR5 mRNA expression was noticed during primary SIVmac251 infection of
      macaques, mainly in tissue. In the three different compartments investigated, IFN
      gamma and RANTES overexpression was noticed by the time of systemic viral
      replication containment. Our results put CCR5 and RANTES mRNA expression back in
      the context of inflammatory and immune responses to SIV primary infection.

PMID- 10069955
TI  - Natural selection of the Pol gene of bovine immunodeficiency virus.
AB  - Genetic variability is a salient feature of lentiviruses, contributing to the
      pathogenesis of these viruses by enabling them to persist in the host and to
      resist anti-retroviral treatment. Bovine immunodeficiency virus (BIV), a
      lentivirus of unknown pathology, infects cattle in the United States and
      worldwide. Genetic diversity of BIV that is associated with naturally infected
      cattle is not well studied. We examined the genetic diversity and natural
      selection of a segment of the BIV pol gene amplified from the leukocyte DNA of
      naturally infected cattle. A portion of the reverse transcriptase domain (183 bp)
      of the pol region was targeted for amplification by PCR. PCR products were
      sequenced directly and aligned. When compared to the sequences of BIV R29-127, a
      molecular clone of the original BIV R29 isolate, all isolates were greater than
      91% identical in nucleotide sequences and 77% identical in amino acid sequences.
      Pol genotypes were polymorphic at 14% of the nucleotide sites. The ratio of
      nonsynonymous to synonymous nucleotide substitutions (relative to the number of
      respective sites, Ka/Ks) was 0.16, indicating that this region of the BIV genome,
      like that of HIV-1, is subject to purifying selection. Based on the McDonald
      Kreitman analysis, this region also was under positive Darwinian selection as HIV
      1 and BIV diverged from a common progenitor. Phylogenetic analysis revealed that
      genotypes were geographically distinct, possibly indicating a common source of
      infection for animals within a herd.

PMID- 10069956
TI  - Expression of hepatitis C virus cDNA in human hepatoma cell line mediated by a
      hybrid baculovirus-HCV vector.
AB  - Although great progress has been made in the characterization of the biochemical
      and biological features of hepatitis C virus (HCV) gene expression, the
      elucidation of the HCV life cycle and the evaluation of novel antiviral
      strategies have been hindered by the lack of a suitable cell culture system. In
      this context, the development of an efficient HCV cDNA delivery method would
      contribute to the understanding of HCV replication. To assess the functionality
      of baculovirus mediated gene delivery for HCV expression, we have constructed
      recombinant baculoviruses encoding HCV cDNA under the control of the
      cytomegalovirus promoter. Transduction of the human hepatoma cell line Huh-7 with
      Bac-HCV vectors was efficient and HCV cDNA expression was enhanced by treatment
      of the infected cells with dexamethasone. HCV structural and nonstructural
      polypeptides were processed correctly and were found to localize in the cytoplasm
      in a pattern characteristic of the endoplasmic reticulum. The expression of the
      HCV proteins was detected for 49 days after infection. Thus, these results
      indicate that the recombinant Bac-HCV vectors are a useful tool for the delivery
      of HCV cDNA and can facilitate the analysis of structural and functional
      properties of the HCV proteins. In addition, the Bac-HCV vectors can provide
      important information on the evaluation of novel anti-HCV antiviral strategies.

PMID- 10069957
TI  - Heterologous sequences greatly affect foreign gene expression in tobacco mosaic
      virus-based vectors.
AB  - A series of tobacco mosaic virus (TMV)-based hybrid vectors for transient gene
      expression were constructed with similar designs but differing in the source of
      heterologous tobamovirus sequence: Odontoglossum ringspot virus, tobacco mild
      green mosaic virus variants U2 and U5, tomato mosaic virus, and sunn-hemp mosaic
      virus. These vectors contained a heterologous coat protein subgenomic mRNA
      promoter and coat protein open reading frame (ORF) and either TMV or heterologous
      3' nontranslated region. The foreign ORF, from the jellyfish green fluorescent
      protein (GFP) gene, was transcribed from the native TMV coat protein subgenomic
      mRNA promoter, which extended into the coat protein ORF. The presence of an in
      frame stop codon within the GFP mRNA leader and the choice of sequence of GFP
      ORFs substantially affected translational efficiency. However, the major
      regulatory component of gene expression in these vectors appeared to be
      transcriptional rather than translational. There was an inverse relationship
      between expression of GFP and the heterologous coat protein genes that was
      reflected in accumulation of the respective mRNAs and proteins. The most
      effective vector in this series (30B) contained sequences encoding the coat
      protein subgenomic mRNA promoter, coat protein ORF, and 3' nontranslated region
      from tobacco mild green mosaic virus U5. Expressed from 30B, GFP accumulated up
      to 10% of total soluble protein in leaves.

PMID- 10069958
TI  - Involvement of the aphthovirus RNA region located between the two functional AUGs
      in start codon selection.
AB  - Initiation of translation in picornavirus RNAs occurs internally, mediated by an
      element termed internal ribosome entry site (IRES). In the aphthovirus RNA, the
      IRES element directs translation initiation at two in-frame AUGs separated by 84
      nucleotides. We have found that bicistronic constructs that contained the IRES
      element followed by the fragment including the aphthovirus start codons in front
      of the second gene mimicked the translation initiation pattern of viral RNA
      observed in infected cells. In those constructs, the frequency of initiation at
      the first AUG was increased by a sequence context that resembled the favorable
      consensus for cap-dependent translation, although initiation at the second site
      was always preferred. In addition, we have found that initiation at the second
      start codon was not diminished under conditions in which the first initiation
      codon was blocked by antisense oligonucleotide interference. Interestingly,
      mutations that positioned the second AUG out-of-frame with the first AUG did not
      interfere with the frequency of initiation at the second one. On the contrary,
      IRES-dependent translation initiation in bicistronic constructs lacking the
      sequences present between functional AUGs in the viral RNA was sensitive to the
      presence of out-of-frame initiator codons and hairpins in the spacer region. This
      remarkable difference in start codon recognition was due to the nucleotide
      composition of the RNA that separated the IRES from the initiator codon. Thus our
      results indicate that the region located in the aphthovirus RNA between
      functional AUGs is involved in start codon recognition, strongly favoring
      selection of the second start AUG as the main initiator codon.

PMID- 10069959
TI  - Human immunodeficiency virus type 1 Tat-dependent activation of an arrested RNA
      polymerase II elongation complex.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein is a transcriptional
      activator that is essential for efficient viral gene expression and replication.
      Tat increases the level of full-length transcripts from the HIV-1 promoter by
      dramatically enhancing the elongation efficiency of the RNA polymerase II
      complexes assembled on this promoter. Tat could potentially activate the
      transcription machinery during initiation, elongation, or both. We used an
      immobilized HIV-1 promoter template with a reversible lac repressor (LacR)
      elongation block inserted downstream to dissect the stages in transcription
      affected by Tat. Transcription complexes assembled in the absence of Tat and
      blocked by LacR cannot be activated by incubation with Tat alone. These complexes
      can, however, be activated if Tat is added in combination with cellular factors.
      In this system, Tat also promoted the assembly of preinitiation complexes capable
      of elongating efficiently, suggesting that Tat can associate with transcription
      complex at an early stage. These data indicate that Tat can activate elongation
      of RNA polymerase by modifying an already elongating transcription complex. The
      data also suggest the possibility that Tat can interact with initiation
      complexes.

PMID- 10069960
TI  - Induction of a protective antibody response to foot and mouth disease virus in
      mice following oral or parenteral immunization with alfalfa transgenic plants
      expressing the viral structural protein VP1.
AB  - The utilization of transgenic plants expressing recombinant antigens to be used
      in the formulation of experimental immunogens has been recently communicated. We
      report here the development of transgenic plants of alfalfa expressing the
      structural protein VP1 of foot and mouth disease virus (FMDV). The presence of
      the transgenes in the plants was confirmed by PCR and their specific
      transcription was demonstrated by RT-PCR. Mice parenterally immunized using leaf
      extracts or receiving in their diet freshly harvested leaves from the transgenic
      plants developed a virus-specific immune response. Animals immunized by either
      method elicited a specific antibody response to a synthetic peptide representing
      amino acid residues 135-160 of VP1, to the structural protein VP1, and to intact
      FMDV particles. Additionally, the immunized mice were protected against
      experimental challenge with the virus. We believe this is the first report
      demonstrating the induction of a protective systemic antibody response in animals
      fed transgenic plants expressing a viral antigen. These results support the
      feasibility of producing edible vaccines in transgenic forage plants, such as
      alfalfa, commonly used in the diet of domestic animals even for those antigens
      for which a systemic immune response is required.

PMID- 10069961
TI  - In vivo detection, RNA-binding properties and characterization of the RNA-binding
      domain of the p7 putative movement protein from carnation mottle carmovirus
      (CarMV).
AB  - Biochemical and structural characterization studies on the p7 putative movement
      protein from a Spanish isolate of carnation mottle carmovirus (CarMV) have been
      conducted. The CarMV p7 gene was fused to a sequence coding for a six-histidine
      tag and expressed in bacteria, allowing the purification of CarMV p7 and the
      production of a specific antiserum. This antiserum led to the immunological
      identification of CarMV p7 in infected leaf tissue from the experimental host
      Chenopodium quinoa. Putative nucleic acid-binding properties of the CarMV p7 have
      been explored and demonstrated with both electrophoretic mobility shift and RNA
      protein blot in vitro assays using digoxigenin-labeled riboprobes. CarMV p7 did
      not show preferential binding to any of the different regions of the CarMV
      genomic RNA tested, suggesting that RNA binding was sequence nonspecific.
      Quantitative analyses of the data allowed calculation of the apparent
      dissociation constant of the p7-RNA complex (Kd approximately 0.7 microM) and
      supported a cooperative type of binding. A small 19-amino-acid synthetic peptide
      whose sequence corresponds to the putative RNA-binding domain of CarMV p7, at the
      basic central part of the protein, was synthesized, and it was demonstrated that
      it binds viral RNA probes. Peptide RNA binding was as stable as p7 binding,
      although data indicated it was not cooperative, thus suggesting that this
      cooperative binding requires another motif or motifs within the p7 amino acid
      sequence. The peptide could be induced to fold into an alpha-helix structure in
      which amino acids that are conserved among carmovirus p7-like proteins are
      distributed on one side. This alpha-helix motif could define a new and previously
      uncharacterized RNA-binding domain for plant virus movement proteins.

PMID- 10069962
TI  - Noncytopathic flavivirus replicon RNA-based system for expression and delivery of
      heterologous genes.
AB  - Noncytopathic replicons of the flavivirus Kunjin (KUN) were employed for
      expression and delivery of heterologous genes. Replicon vector C20DX2Arep,
      containing a unique cloning site followed by the sequence of 2A autoprotease of
      foot-and-mouth disease virus, was constructed and used for expression of a number
      of heterologous genes including chloramphenicol acetyltransferase (CAT), green
      fluorescent protein (GFP), beta-galactosidase, glycoprotein G of vesicular
      stomatitis virus, and the Core and NS3 genes of hepatitis C virus. The expression
      and proper processing of these genes upon transfection of BHK21 cells with the
      recombinant replicon RNAs were demonstrated by immunofluorescence,
      radioimmunoprecipitation, and appropriate reporter gene assays. Most of these
      recombinant KUN replicon RNAs were also successfully packaged into secreted virus
      like particles (VLPs) by subsequent transfection with Semliki Forest virus
      replicon RNA expressing KUN structural genes. Infection of BHK21 and Vero cells
      with these VLPs resulted in continuous replication of the recombinant replicon
      RNAs and prolonged expression of the cloned genes without any cytopathic effect.
      We also developed a replicon vector for generation of stable cell lines
      continuously expressing heterologous genes by inserting an encephalomyelocarditis
      virus internal ribosomal entry site-neomycin transferase gene cassette into the
      3'-untranslated region of the C20DX2Arep vector. Using this vector
      (C20DX2ArepNeo), stable BHK cell lines persistently expressing GFP and CAT genes
      for up to 17 passages were established. Thus noncytopathic KUN replicon vectors
      with the ability to be packaged into VLPs should provide a useful tool for the
      development of noninfectious and noncytopathic vaccines as well as for gene
      therapy applications.

PMID- 10069963
TI  - Genetic variation of chlorella viruses: variable regions localized on the CVK2
      genomic DNA.
AB  - A physical map of the Chlorella virus CVK2 genomic DNA has been constructed based
      on a cosmid contig covering the entire genomic region. By using Southern blot
      analysis with 22 gene probes, the gene arrangement along the genome was compared
      between CVK2 and PBCV-1, the prototypic member of Phycodnaviridae, whose genomic
      sequence is now available. The major rearrangements were (1) an insertion of a 20
      kbp region around the left end of CVK2 DNA, (2) a duplication of the gene for
      major capsid protein in CVK2 DNA, (3) deletions/insertions of some open reading
      frames, and (4) divergence in the terminal inverted repeat sequences. Despite
      these changes, extensive colinearity was revealed between most of the genes along
      the CVK2 and PBCV-1 genomes. These data imply that the Chlorella virus genome has
      an overall high degree of genomic stability, encompassing specific islands of
      rearrangements.

PMID- 10069964
TI  - A mutational analysis of the transforming functions of the E8 protein of bovine
      papillomavirus type 4.
AB  - The E8 protein of BPV-4 contributes to transformation of primary bovine cells
      (PalFs) by inducing anchorage-independent growth and by down-regulating gap
      junction intercellular communication, likely due to its binding to 16K ductin. We
      show here that, in addition, E8 confers on PalF cells the ability to grow in low
      serum and to escape from contact inhibition (focus formation). E8 also
      transactivates an exogenous human cyclin A gene promoter, suggesting that
      overexpression of cyclin A is responsible for the transformed phenotype. Mutant
      forms of E8 were generated to establish whether the transforming functions of the
      protein could be segregated. Mutations were introduced both in the hydrophobic
      domain and in the hydrophilic C-terminal "tail", and chimeras with BPV-1 E5 were
      constructed. Cells expressing either wild-type E8 or mutant forms were analyzed
      for their ability to grow in low serum and in suspension and to form foci. Wild
      type E8 and its mutants were also analyzed for their ability to transactivate the
      cyclin A promoter. We show here that the transforming functions of E8 can be
      segregated and that both the hydrophilic C-terminal tail and the residue at
      position 17 in the hydrophobic domain are crucial for E8 functions and for the
      transactivation of the cyclin A promoter. These results support the hypothesis
      that the different aspects of cellular transformation brought about by E8 might
      be due to interaction with different cellular targets. They suggest that E8 might
      function differently from BPV-1 E5 and demonstrate that the separate domains of
      E5 and E8 are not functionally interchangeable.

PMID- 10069965
TI  - How polarization-sensitive interneurones of crickets see the polarization pattern
      of the sky: a field study with an opto-electronic model neurone 
AB  - Many insects gain directional information from the polarization pattern of the
      sky. Polarization vision is mediated by the specialized ommatidia of the dorsal
      rim area of the compound eye, which contains highly polarization-sensitive
      photoreceptors. In crickets Gryllus campestris, polarized light information
      conveyed by the dorsal rim ommatidia was found to be processed by polarization
      opponent interneurones (POL-neurones). In this study, a field-proof opto
      electronic model of a POL-neurone was constructed that implements the
      physiological properties of cricket POL-neurones as measured by previous
      electrophysiological experiments in the laboratory. Using this model neurone,
      both the strength of the celestial polarization signal and the directional
      information available to POL-neurones were assessed under a variety of
      meteorological conditions. We show that the polarization signal as experienced by
      cricket POL-neurones is very robust, both because of the special filtering
      properties of these neurones (polarization-antagonism, spatial low-pass,
      monochromacy) and because of the relatively stable e-vector pattern of the sky.

PMID- 10069966
TI  - Morphology and mechanics of tongue movement in the African pig-nosed frog Hemisus
      marmoratum: a muscular hydrostatic model.
AB  - The goal of this study was to investigate morphological adaptations associated
      with hydrostatic elongation of the tongue during feeding in the African pig-nosed
      frog Hemisus marmoratum. Whereas previous studies had suggested that the tongue
      of H. marmoratum elongates hydraulically, the anatomical observations reported
      here favour a muscular hydrostatic mechanism of tongue elongation. H. marmoratum
      possesses a previously undescribed compartment of the m. genioglossus (m.
      genioglossus dorsoventralis), which is intrinsic to the tongue and whose muscle
      fibres are oriented perpendicular to the long axis of the tongue. On the basis of
      the arrangement and orientation of muscle fibres in the m. genioglossus and m.
      hyoglossus, we propose a muscular hydrostatic model of tongue movement in which
      contraction of the m. genioglossus dorsoventralis, together with unfolding of the
      intrinsic musculature of the tongue, results in a doubling in tongue length.
      Electron micrographs of sarcomeres from resting and elongated tongues show that
      no special adaptations of the sarcomeres are necessary to accommodate the
      observed doubling in tongue length during feeding. Rather, the sarcomeres of the
      m. genioglossus longitudinalis are strikingly similar to those of anuran limb
      muscles. The ability to elongate the tongue hydrostatically, conferred by the
      presence of the m. genioglossus dorsoventralis, is associated with the appearance
      of several novel aspects of feeding behaviour in H. marmoratum. These include the
      ability to protract the tongue slowly, thereby increasing capture success, and
      the ability to aim the tongue in azimuth and elevation relative to the head.
      Compared with other frogs, the muscular hydrostatic system of H. marmoratum
      allows more precise, localized and diverse tongue movements. This may explain why
      the m. genioglossus of H. marmoratum is composed of a larger number of motor
      units than that of other frogs.

PMID- 10069967
TI  - Development of diving capacity in emperor penguins.
AB  - To compare the diving capacities of juvenile and adult emperor penguins
      Aptenodytes forsteri, and to determine the physiological variables underlying the
      diving ability of juveniles, we monitored diving activity in juvenile penguins
      fitted with satellite-linked time/depth recorders and examined developmental
      changes in body mass (Mb), hemoglobin concentration, myoglobin (Mb) content and
      muscle citrate synthase and lactate dehydrogenase activities. Diving depth,
      diving duration and time-at-depth histograms were obtained from two fledged
      juveniles during the first 2.5 months after their depature from the Cape
      Washingon colony in the Ross Sea, Antarctica. During this period, values of all
      three diving variables increased progressively. After 8-10 weeks at sea, 24-41 %
      of transmitted maximum diving depths were between 80 and 200 m. Although most
      dives lasted less than 2 min during the 2 month period, 8-25 % of transmitted
      dives in the last 2 weeks lasted 2-4 min. These values are lower than those
      previously recorded in adults during foraging trips. Of the physiological
      variables examined during chick and juvenile development, only Mb and Mb content
      did not approach adult values. In both near-fledge chicks and juveniles, Mb was
      50-60 % of adult values and Mb content was 24-31 % of adult values. This suggests
      that the increase in diving capacity of juveniles at sea will be most dependent
      on changes in these factors.

PMID- 10069968
TI  - Respecified larval proleg and body wall muscles circulate hemolymph in developing
      wings of Manduca sexta pupae.
AB  - Most larval external muscles in Manduca sexta degenerate at pupation, with the
      exception of the accessory planta retractor muscles (APRMs) in proleg-bearing
      abdominal segment 3 and their homologs in non-proleg-bearing abdominal segment 2.
      In pupae, these APRMs exhibit a rhythmic 'pupal motor pattern' in which all four
      muscles contract synchronously at approximately 4 s intervals for long bouts,
      without externally visible movements. On the basis of indirect evidence, it was
      proposed previously that APRM contractions during the pupal motor pattern
      circulate hemolymph in the developing wings and legs. This hypothesis was tested
      in the present study by making simultaneous electromyographic recordings of APRM
      activity and contact thermographic recordings of hemolymph flow in pupal wings.
      APRM contractions and hemolymph flow were strictly correlated during the pupal
      motor pattern. The proposed circulatory mechanism was further supported by the
      findings that unilateral ablation of APRMs or mechanical uncoupling of the wings
      from the abdomen essentially abolished wing hemolymph flow on the manipulated
      side of the body. Rhythmic contractions of intersegmental muscles, which
      sometimes accompany the pupal motor pattern, had a negligible effect on hemolymph
      flow. The conversion of larval proleg and body wall muscles to a circulatory
      function in pupae represents a particularly dramatic example of functional
      respecification during metamorphosis.

PMID- 10069969
TI  - Optimizing force and velocity: mandible muscle fibre attachments in ants 
AB  - To be able to perform swift and powerful movements, ant mandible closer muscles
      are composed of two subpopulations of muscle fibres: fast fibres for rapid
      actions and slow fibres for forceful biting. All these fibres attach to a sturdy
      and complex apodeme which conveys force into the mandible base. Fast muscle
      fibres attach directly to the apodeme. Slow fibres may attach directly or insert
      at individual thin filament processes of the apodeme which vary in length.
      Comparisons of different ant species suggest two basic principles underlying the
      design of mandible muscles. (1) Ants specialized for fast mandible movements
      generally feature long heads which contain long fast muscle fibres that attach to
      the apodeme at small angles. Their muscles comprise only a few filament-attached
      fibres and they maximize speed of action at the expense of force output. (2) Ants
      performing particularly forceful mandible movements, such as seed cracking, rely
      on many short parallel muscle fibres contained within a broad head capsule. Their
      slower muscles incorporate a large proportion of filament-attached fibres. Two
      simple models explain how the attachment angles are optimized with respect to
      force and velocity output and how filament-attached fibres help to generate the
      largest power output from the available head capsule volume.

PMID- 10069970
TI  - Purification and cloning of the salivary peroxidase/catechol oxidase of the
      mosquito Anopheles albimanus.
AB  - Salivary homogenates of the adult female mosquito Anopheles albimanus have been
      shown previously to contain a vasodilatory activity associated with a catechol
      oxidase/peroxidase activity. We have now purified the salivary peroxidase using
      high-performance liquid chromatography. The pure enzyme is able to relax rabbit
      aortic rings pre-constricted with norepinephrine. The peroxidase has a relative
      molecular mass of 66 907 as estimated by mass spectrometry. Amino-terminal
      sequencing allowed us to design oligonucleotide probes for isolation of cDNA
      clones derived from the salivary gland mRNA from female mosquitoes. The full
      sequence of the cDNA demonstrated homology between A. albimanus salivary
      peroxidase and several members of the myeloperoxidase gene family. A close
      comparison of A. albimanus salivary peroxidase with canine myeloperoxidase, for
      which the crystal structure is known, showed that all six disulfide bridges were
      conserved and demonstrated identity for all five residues associated with a Ca2+
      binding site. In addition, 16 of 26 residues shown to be in close proximity to
      the heme moiety in the canine myeloperoxidase were identical. We conclude that
      the salivary peroxidase of A. albimanus belongs to the myeloperoxidase gene
      family. Other possible functions for this molecule in blood feeding are
      discussed.

PMID- 10069971
TI  - Changes in motor network expression related to moulting behaviour in lobster:
      role of moult-induced deep hypoxia 
AB  - The well known rhythmically active pyloric neural network in intact and freely
      behaving lobsters Homarus gammarus was monitored prior to and following ecdysis.
      Despite long-lasting hormonal and metabolic alterations associated with this
      process, spontaneous pyloric network activity remained largely unaltered until
      the last 12-48 h before exuviation. At this time, the most notable change was a
      progressive lengthening of pyloric cycle period, which eventually attained 500
      600 % of control values. It was only in the very last minutes before ecdysis that
      burst patterning became irregular and the otherwise strictly alternating motor
      sequence broke down. After the moult, coordinated rhythmicity was re-established
      within 10 min. Concomitant with these final changes in motor network expression
      at ecdysis was a drastic reduction in blood oxygen levels which led to a
      temporary near-anoxia. By imposing similarly deep hypoxic conditions both on
      intermoult animals and on the pyloric network in vitro, we mimicked to a large
      extent the moult-induced changes in pyloric network performance. Our data suggest
      that, despite major surrounding physiological perturbations, the pyloric network
      in vivo retains stable pattern-generating properties throughout much of the
      moulting process. Moreover, some of the most significant modifications in motor
      expression just prior to ecdysis can be related to a substantial reduction in
      oxygen levels in the blood.

PMID- 10069972
TI  - Brain blood flow and blood pressure during hypoxia in the epaulette shark
      Hemiscyllium ocellatum, a hypoxia-tolerant elasmobranch.
AB  - The key to surviving hypoxia is to protect the brain from energy depletion. The
      epaulette shark (Hemiscyllium ocellatum) is an elasmobranch able to resist energy
      depletion and to survive hypoxia. Using epi-illumination microscopy in vivo to
      observe cerebral blood flow velocity on the brain surface, we show that cerebral
      blood flow in the epaulette shark is unaffected by 2 h of severe hypoxia (0.35 mg
      O2 l-1 in the respiratory water, 24 C). Thus, the epaulette shark differs from
      other hypoxia- and anoxia-tolerant species studied: there is no adenosine
      mediated increase in cerebral blood flow such as that occurring in freshwater
      turtles and cyprinid fish. However, blood pressure showed a 50 % decrease in the
      epaulette shark during hypoxia, indicating that a compensatory cerebral
      vasodilatation occurs to maintain cerebral blood flow. We observed an increase in
      cerebral blood flow velocity when superfusing the normoxic brain with adenosine
      (making sharks the oldest vertebrate group in which this mechanism has been
      found). The adenosine-induced increase in cerebral blood flow velocity was
      reduced by the adenosine receptor antagonist aminophylline. Aminophylline had no
      effect upon the maintenance of cerebral blood flow during hypoxia, however,
      indicating that adenosine is not involved in maintaining cerebral blood flow in
      the epaulette shark during hypoxic hypotension.

PMID- 10069973
TI  - Urine release in freely moving catheterised lobsters (Homarus americanus) with
      reference to feeding and social activities.
AB  - Previous studies suggest that urine-borne pheromones play an important role in
      lobster agonistic and sexual behaviour. This paper investigates the pattern of
      urine release in catheterised, but otherwise freely moving, adult lobsters with
      respect to feeding, social and non-social activities. Lobsters on average
      released 4.1 ml (1 % of body mass) of urine over a 12 h period; this more than
      doubled to 10.6 ml over the 12 h period after feeding. Hourly monitoring revealed
      that most urine was released in the first hour after feeding (2.84 ml). With the
      exception of the first hours after feeding, urine release was intermittent, with
      pauses lasting up to 17 h. The probability of urine release per hour in unfed
      lobsters was 0.34 (median); this value increased during agonistic interactions
      elicited by the introduction of a conspecific (median 0. 63) and during activity
      initiated by non-social disturbance (median 0.56). Mean urine volume during
      output hours in unfed lobsters amounted to 1.09 ml h-1. This volume was
      significantly increased by the presence of a conspecific (1.88 ml h-1) and
      decreased during activity initiated by non-social disturbances (0.56 ml h-1). No
      sex-specific differences in urine release were found. The data demonstrate that
      lobsters control their urine release in a manner dependent on behavioural
      context. This supports recent findings suggesting the use of urine for chemical
      signalling in agonistic interactions.

PMID- 10069974
TI  - Water skating in the larvae of dixella aestivalis (Diptera) and hydrobius
      fuscipes (Coleoptera) 
AB  - The kinematics of locomotion was investigated in the aquatic larvae of Dixella
      aestivalis and Hydrobius fuscipes with the aid of high-speed video recordings.
      Both insects are able to skate on the surface of the water using the dorso-apical
      tracheal gill as an adhesive organ or 'foot'. Progress relies on the variable
      adhesion of the foot between 'slide' and 'hold' periods of the locomotory cycle.
      The flexural body movements underlying skating in D. aestivalis can be derived
      directly from the figure-of-eight swimming mechanism used in underwater swimming.
      The latter is shown to be similar to figure-of-eight swimming in chironomid
      larvae. This study shows how the deployment of a 'foot' enables simple side-to
      side flexural movements of the body to be converted into effective locomotion at
      the air-water interface.

PMID- 10069975
TI  - Excretion of thiosulphate, the main detoxification product of sulphide, by the
      lugworm arenicola marina L 
AB  - Thiosulphate, the main sulphide detoxification product, is accumulated in the
      body fluids of the lugworm Arenicola marina. The aim of this study was to
      elucidate the fate of thiosulphate. Electrophysiological measurements revealed
      that the transepithelial resistance of body wall sections was 76+/-34 capomega
      cm2 (mean +/- s.d., N=14), indicating that the body wall of the lugworm is a
      leaky tissue in which mainly paracellular transport along cell junctions takes
      place. The body wall was equally permeable from both sides to thiosulphate, the
      permeability coefficient of which was 1. 31x10(-)3+/-0.37x10(-)3 cm h-1 (mean +/-
      s.d., N=30). No evidence was found for a significant contribution of the gills or
      the nephridia to thiosulphate permeation. Thiosulphate flux followed the
      concentration gradient, showing a linear correlation (r=0.997) between permeated
      and supplied (10-100 mmol l-1) thiosulphate. The permeability of thiosulphate was
      not sensitive to the presence of various metabolic inhibitors, implicating a
      permeation process independent of membrane proteins and showing that the lugworm
      does not need to use energy to dispose of the sulphide detoxification product.
      The present data suggest a passive permeation of thiosulphate across the body
      wall of A. marina. In live lugworms, thiosulphate levels in the coelomic fluid
      and body wall tissue decreased slowly and at similar rates during recovery from
      sulphide exposure. The decline in thiosulphate levels followed a decreasing
      double-exponential function. Thiosulphate was not further oxidized to sulphite or
      sulphate but was excreted into the sea water.

PMID- 10069976
TI  - Evolution of complexity in motor patterns and jaw musculature of tetraodontiform
      fishes 
AB  - The prey-processing behavior and jaw-adducting musculature of tetraodontiform
      fishes provide a novel system for studying the evolution of muscles and their
      function. The history of this clade has involved a pattern of repeated
      'duplications' of jaw muscles by physical subdivision of pre-existing muscles. As
      a result, the number of adductor mandibulae muscles in different taxa varies from
      as few as two to as many as eight. We used electromyography (EMG) to quantify
      motor-pattern variation of adductor mandibulae muscles in four tetraodontiform
      species during feeding events on prey items that varied in durability and
      elusiveness. Statistical analyses of variation in EMG variables revealed
      significant differences in motor patterns between duplicated muscles derived from
      a common ancestral muscle in seven of nine cases examined. Overall individual EMG
      timing variables (e.g. relative onset or duration of bursts) were slightly less
      likely to diverge functionally than amplitude variables (e.g. relative intensity
      of bursts). Functional divergence was found in significant overall differences
      between muscles and twice as frequently in significant muscle-by-prey interaction
      terms. Such interactions represent an underappreciated way in which motor
      patterns can evolve and diversify. Regional variation was documented in undivided
      muscles in two species, indicating that it is possible for functional subdivision
      to precede anatomical subdivision. This study shows that phylogenetic increases
      in the number of tetraodontiform jaw adductor muscles have been associated with
      increases in the functional complexity of the jaws at the level of muscle
      activation patterns.

PMID- 10069977
TI  - The sarcoplasmic reticulum plays a major role in isometric contraction in atrial
      muscle of yellowfin tuna 
AB  - We used an isometric muscle preparation to test the hypothesis that yellowfin
      tuna Thunnus albacares utilize the intracellular Ca2+ storage sites of the
      sarcoplasmic reticulum (SR) during routine contractions. Ryanodine (a blocker of
      SR Ca2+ release) reduced the force of contraction by approximately 50 % and the
      rates of contraction and relaxation by 60 % in yellowfin tuna atrium. High levels
      of adrenaline were unable to ameliorate the effects of ryanodine. We conclude
      that the SR is active in contributing Ca2+ to force development at physiological
      contraction frequencies. Further, we suggest that, by using intracellular Ca2+
      cycling, the yellowfin tuna is able to increase the maximum contraction frequency
      of its cardiac muscle beyond that of most other fishes.

PMID- 10069978
TI  - Genetic and biochemical determinants of abnormal monovalent ion transport in
      primary hypertension.
AB  - Data obtained during the last two decades show that spontaneously hypertensive
      rats, an acceptable experimental model of primary human hypertension, possess
      increased activity of both ubiquitous and renal cell-specific isoforms of the
      Na+/H+ exchanger (NHE) and Na+-K+-2Cl- cotransporter. Abnormalities of these ion
      transporters have been found in patients suffering from essential hypertension.
      Recent genetic studies demonstrate that genes encoding the beta- and gamma
      subunits of ENaC, a renal cell-specific isoform of the Na+-K+-2Cl- cotransporter,
      and alpha3-, alpha1-, and beta2-subunits of the Na+-K+ pump are localized within
      quantitative trait loci (QTL) for elevated blood pressure as well as for enhanced
      heart-to-body weight ratio, proteinuria, phosphate excretion, and stroke latency.
      On the basis of the homology of genome maps, several other genes encoding these
      transporters, as well as the Na+/H+ exchanger and Na+-K+-2Cl- cotransporter, can
      be predicted in QTL related to the pathogenesis of hypertension. However, despite
      their location within QTL, analysis of cDNA structure did not reveal any mutation
      in the coding region of the above-listed transporters in primary hypertension,
      with the exception of G276L substitution in the alpha1-Na+-K+ pump from Dahl salt
      sensitive rats and a higher occurrence of T594M mutation of beta-ENaC in the
      black population with essential hypertension. These results suggest that, in
      contrast to Mendelian forms of hypertension, the altered activity of monovalent
      ion transporters in primary hypertension is caused by abnormalities of systems
      involved in the regulation of their expression and/or function. Further analysis
      of QTL in F2 hybrids of normotensive and hypertensive rats and in affected
      sibling pairs will allow mapping of genes causing abnormalities of these
      regulatory pathways.

PMID- 10069979
TI  - CCK receptor trafficking: a novel paradigm of travel focus on "regulation of
      lateral mobility and cellular trafficking of the CCK receptor by a partial
      agonist".

PMID- 10069980
TI  - Regulation of lateral mobility and cellular trafficking of the CCK receptor by a
      partial agonist.
AB  - Partial agonists are effective tools for advancing development of highly
      selective drugs and providing insights into molecular regulation of cellular
      functions. Here, we explore the impact of a partial agonist on key aspects of
      cholecystokinin (CCK) receptor regulation, its lateral mobility and cellular
      trafficking, in native pancreatic acinar cells and Chinese hamster ovary cells
      expressing CCK receptor (CHO-CCKR). We developed and characterized a novel
      fluorescent partial agonist, rhodamine-Gly-[(Nle28, 31)CCK-26-32]-phenethyl
      ester, that binds specifically and with high affinity to CCK receptors. Such
      analogs are fully efficacious pancreatic acinar cell secretagogues without
      supramaximal inhibition that mobilize intracellular calcium with little or no
      increase in phospholipase C (PLC) activity. Despite minimal phosphorylation of
      CCK receptors in response to this partial agonist, receptor trafficking was the
      same as that observed with full agonist (CCK). This included normal
      internalization via clathrin-dependent endocytosis in CHO-CCKR cells and
      insulation on the surface of pancreatic acinar cells. Also, as with CCK-occupied
      receptor, fluorescence recovery after photobleaching of partial agonist-occupied
      receptor on the acinar cell surface demonstrated a marked temperature-dependent
      slowing of its rate of diffusion. This was similarly associated with resistance
      to acid-induced dissociation of ligand. Thus some key molecular regulatory
      mechanisms for CCK receptor internalization and insulation may be initiated by
      cellular signaling cascades that are not dependent on PLC activation or receptor
      phosphorylation.

PMID- 10069981
TI  - Transport of fluid by lens epithelium.
AB  - We report for the first time that cultured lens epithelial cell layers and rabbit
      lenses in vitro transport fluid. Layers of the alphaTN4 mouse cell line and
      bovine cell cultures were grown to confluence on permeable membrane inserts.
      Fluid movement across cultured layers and excised rabbit lenses was determined by
      volume clamp (37 degrees C). Cultured layers transported fluid from their basal
      to their apical sides against a pressure head of 3 cmH2O. Rates were (in
      microliter. h-1. cm-2) 3.3 +/- 0.3 for alphaTN4 cells (n = 27) and 4.7 +/- 1.0
      for bovine layers (n = 6). Quinidine, a blocker of K+ channels, and p
      chloromercuribenzenesulfonate and HgCl2, inhibitors of aquaporins, inhibited
      fluid transport. Rabbit lenses transported fluid from their anterior to their
      posterior sides against a 2.5-cmH2O pressure head at 10.3 +/- 0.62 microliter. h
      1. lens-1 (n = 5) and along the same pressure head at 12.5 +/- 1.1 microliter. h
      1. lens-1 (n = 6). We calculate that this flow could wash the lens extracellular
      space by convection about once every 2 h and therefore might contribute to lens
      homeostasis and transparency.

PMID- 10069982
TI  - Direct evidence of Na+/Ca2+ exchange in squid rhabdomeric membranes.
AB  - Na+/Ca2+ exchange has been investigated in squid (Loligo pealei) rhabdomeric
      membranes. Ca2+-containing vesicles have been prepared from purified rhabdomeric
      membranes by extrusion through polycarbonate filters of 1-micrometer pore size.
      After removal of external Ca2+, up to 90% of the entrapped Ca2+ could be
      specifically released by the addition of Na+; this finding indicates that most of
      the vesicles contained Na+/Ca2+ exchanger. The Na+-induced Ca2+ efflux had a half
      maximum value (K1/2) of approximately 44 mM and a Hill coefficient of
      approximately 1.7. The maximal Na+-induced Ca2+ efflux was approximately 0.6 nmol
      Ca2+. s-1. mg protein-1. Similar Na+-induced Ca2+ effluxes were measured if K+
      was replaced with Li+ or Cs+. Vesicles loaded with Ca2+ by Na+/Ca2+ exchange also
      released this Ca2+ by Na+/Ca2+ exchange, suggesting that Na+/Ca2+ exchange
      operated in both forward and reverse modes. Limited proteolysis by trypsin
      resulted in a rate of Ca2+ efflux enhanced by approximately fivefold when efflux
      was activated with 95 mM NaCl. For vesicles subjected to limited proteolysis by
      trypsin, Na+/Ca2+ exchange was characterized by a K1/2 of approximately 25 mM and
      a Hill coefficient of 1.6. For these vesicles, the maximal Na+-induced Ca2+
      efflux was about twice as great as in control vesicles. We conclude that Na+/Ca2+
      exchange proteins localized in rhabdomeric membranes mediate Ca2+ extrusion in
      squid photoreceptors.

PMID- 10069983
TI  - Ca2+ sensitization of smooth muscle contractility induced by ruthenium red.
AB  - The effects of ruthenium red (RuR) on contractility were examined in skinned
      fibers of guinea pig smooth muscles, where sarcoplasmic reticulum function was
      destroyed by treatment with A-23187. Contractions of skinned fibers of the
      urinary bladder were enhanced by RuR in a concentration-dependent manner (EC50 =
      60 microM at pCa 6.0). The magnitude of contraction at pCa 6.0 was increased to
      320% of control by 100 microM RuR. Qualitatively, the same results were obtained
      in skinned fibers prepared from the ileal longitudinal smooth muscle layer and
      mesenteric artery. The maximal contraction induced by pCa 4.5 was not affected
      significantly by RuR. The enhanced contraction by RuR was not reversed by the
      addition of guanosine 5'-O-(2-thiodiphosphate) or a peptide inhibitor of protein
      kinase C [PKC-(19-31)]. The application of microcystin, a potent protein
      phosphatase inhibitor, induced a tonic contraction of skinned smooth muscle at
      low Ca2+ concentration ([Ca2+]; pCa > 8.0). RuR had a dual effect on the
      microcystin-induced contraction-to- enhancement ratio at low concentrations and
      suppression at high concentrations. The relaxation following the decrease in
      [Ca2+] from pCa 5.0 to >8.0 was significantly slowed down by an addition of RuR.
      Phosphorylation of the myosin light chain at pCa 6.3 was significantly increased
      by RuR in skinned fibers of the guinea pig ileum. These results indicate that RuR
      markedly increases the Ca2+ sensitivity of the contractile system, at least in
      part via inhibition of myosin light chain phosphatase.

PMID- 10069984
TI  - Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter
      isoform (hhNBC).
AB  - Our group recently cloned the electrogenic Na+-HCO-3 cotransporter (NBC) from
      salamander kidney and later from mammalian kidney. Here we report cloning an NBC
      isoform (hhNBC) from a human heart cDNA library. hhNBC is identical to human
      renal NBC (hkNBC), except for the amino terminus, where the first 85 amino acids
      in hhNBC replace the first 41 amino acids of hkNBC. About 50% of the amino acid
      residues in this unique amino terminus are charged, compared with approximately
      22% for the corresponding 41 residues in hkNBC. Northern blot analysis, with the
      use of the unique 5' fragment of hhNBC as a probe, shows strong expression in
      pancreas and expression in heart and brain, although at much lower levels. In
      Xenopus oocytes expressing hhNBC, adding 1.5% CO2/10 mM HCO-3 hyperpolarizes the
      membrane and causes a rapid fall in intracellular pH (pHi), followed by a pHi
      recovery. Subsequent removal of Na+ causes a depolarization and a reduced rate of
      pHi recovery. Removal of Cl- from the bath does not affect the pHi recovery. The
      stilbene derivative DIDS (200 microM) greatly reduces the hyperpolarization
      caused by adding CO2/HCO-3. In oocytes expressing hkNBC, the effects of adding
      CO2/HCO-3 and then removing Na+ were similar to those observed in oocytes
      expressing hhNBC. We conclude that hhNBC is an electrogenic Na+-HCO-3
      cotransporter and that hkNBC is also electrogenic.

PMID- 10069985
TI  - Splicing of a retained intron within ROMK K+ channel RNA generates a novel set of
      isoforms in rat kidney.
AB  - The renal outer medulla K+ channel (ROMK) family of K+ channels may constitute a
      major pathway for K+ secretion in the distal nephron. To date, four main isoforms
      of this gene have been identified in the rat that differ only in their NH2
      terminal amino acids and that share a common "core exon" that determines the
      remaining protein sequence. Using RT-PCR, we have identified a new set of ROMK
      isoforms in rat kidney that are generated by the deletion of a region within the
      ROMK core sequence that is identifiable as a typical mammalian intron. This
      splicing event was shown to be reproducible in vitro by detection of deleted ROMK
      mRNA in Madin-Darby canine kidney (MDCK) cells stably transfected with the gene
      for ROMK2. Translation of the deletion variant of ROMK2 was confirmed in vitro
      and visualized in MDCK cells following transient transfection with an enhanced
      green fluorescent protein tag. The deletion in this core region is predicted to
      generate hydrophilic proteins that are approximately one-third of the size of
      native ROMK and lack membrane-spanning domains.

PMID- 10069986
TI  - NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and
      rabbit CB chemoreceptor cells.
AB  - The aim of the present work was to elucidate the role of NADPH oxidase in hypoxia
      sensing and transduction in the carotid body (CB) chemoreceptor cells. We have
      studied the effects of several inhibitors of NADPH oxidase on the normoxic and
      hypoxia-induced release of [3H]catecholamines (CA) in an in vitro preparation of
      intact CB of the rat and rabbit whose CA deposits have been labeled by prior
      incubation with the natural precursor [3H]tyrosine. It was found that
      diphenyleneiodonium (DPI; 0.2-25 microM), an inhibitor of NADPH oxidase, caused a
      dose-dependent release of [3H]CA from normoxic CB chemoreceptor cells. Contrary
      to hypoxia, DPI-evoked release was only partially Ca2+ dependent. Concentrations
      of DPI reported to produce full inhibition of NADPH oxidase in the rat CB did not
      prevent the hypoxic release response in the rat and rabbit CB chemoreceptor
      cells, as stimulation with hypoxia in the presence of DPI elicited a response
      equaling the sum of that produced by DPI and hypoxia applied separately.
      Neopterin (3-300 microM) and phenylarsine oxide (0.5-2 microM), other inhibitors
      of NADPH oxidase, did not promote release of [3H]CA in normoxic conditions or
      affect the response elicited by hypoxia. On the basis of effects of neopterin and
      phenylarsine oxide, it is concluded that NADPH oxidase does not appear to play a
      role in oxygen sensing or transduction in the rat and rabbit CB chemoreceptor
      cells in vitro and, in the context of the present study, that DPI effects are not
      related to NADPH oxidase inhibition.

PMID- 10069987
TI  - Chemical signaling from colonic smooth muscle cells to DRG neurons in culture.
AB  - Transduction mechanisms between target cells within the intestinal wall and
      peripheral terminals of extrinsic primary afferent neurons are poorly understood.
      The purpose of this study was to characterize the interactions between smooth
      muscle cells from the rat distal colon and lumbar dorsal root ganglion (DRG)
      neurons in coculture. DRG neurons visually appeared to make contact with several
      myocytes. We show that brief mechanical stimulation of these myocytes resulted in
      intracellular Ca2+ concentration ([Ca2+]i) transients that propagated into 57% of
      the contacting neurites. Direct mechanical stimulation of DRG neurites cultured
      without smooth muscle had no effect. We also show that colonic smooth muscle
      cells express multiple connexin mRNAs and that these connexins formed functional
      gap junctions, as evidenced by the intercellular transfer of Lucifer yellow.
      Furthermore, thapsigargin pretreatment and neuronal heparin injection abolished
      the increase in neurite [Ca2+]i, indicating that the neuronal Ca2+ signal was
      triggered by inositol 1,4, 5-trisphosphate-mediated Ca2+ release from
      intracellular stores. Our results provide evidence for intercellular chemical
      communication between DRG neurites and intestinal smooth muscle cells that
      mediates the exchange of second messenger molecules between different cell types.

PMID- 10069988
TI  - Rat liver GTP-binding proteins mediate changes in mitochondrial membrane
      potential and organelle fusion.
AB  - The variety of mitochondrial morphology in healthy and diseased cells can be
      explained by regulated mitochondrial fusion. Previously, a mitochondrial outer
      membrane fraction containing fusogenic, aluminum fluoride (AlF4)-sensitive GTP
      binding proteins (mtg) was separated from rat liver (J. D. Cortese, Exp. Cell
      Res. 240: 122-133, 1998). Quantitative confocal microscopy now reveals that mtg
      transiently increases mitochondrial membrane potential (DeltaPsi) when added to
      permeabilized rat hepatocytes (15%), rat fibroblasts (19%), and rabbit myocytes
      (10%). This large mtg-induced DeltaPsi increment is blocked by fusogenic GTPase
      specific modulators such as guanosine 5'-O-(3-thiotriphosphate), excess GTP (>100
      microM), and AlF4, suggesting a linkage between DeltaPsi and mitochondrial
      fusion. Accordingly, stereometric analysis shows that decreasing DeltaPsi or ATP
      synthesis with respiratory inhibitors limits mtg- and AlF4-induced mitochondrial
      fusion. Also, a specific G protein inhibitor (Bordetella pertussis toxin)
      hyperpolarizes mitochondria and leads to a loss of AlF4-dependent mitochondrial
      fusion. These results place mtg-induced DeltaPsi changes upstream of AlF4-induced
      mitochondrial fusion, suggesting that GTPases exert DeltaPsi-dependent control of
      the fusion process. Mammalian mitochondrial morphology thus can be modulated by
      cellular energetics.

PMID- 10069989
TI  - Expression and localization of aquaporins in rat gastrointestinal tract.
AB  - A family of water-selective channels, aquaporins (AQP), has been demonstrated in
      various organs and tissues. However, the localization and expression of the AQP
      family members in the gastrointestinal tract have not been entirely elucidated.
      This study aimed to demonstrate the expression and distribution of several types
      of the AQP family and to speculate on their role in water transport in the rat
      gastrointestinal tract. By RNase protection assay, expression of AQP1-5 and AQP8
      was examined in various portions through the gastrointestinal tract. AQP1 and
      AQP3 mRNAs were diffusely expressed from esophagus to colon, and their expression
      was relatively intense in the small intestine and colon. In contrast, AQP4 mRNA
      was selectively expressed in the stomach and small intestine and AQP8 mRNA in the
      jejunum and colon. Immunohistochemistry and in situ hybridization demonstrated
      cellular localization of these AQP in these portions. AQP1 was localized on
      endothelial cells of lymphatic vessels in the submucosa and lamina propria
      throughout the gastrointestinal tract. AQP3 was detected on the circumferential
      plasma membranes of stratified squamous epithelial cells in the esophagus and
      basolateral membranes of cardiac gland epithelia in the lower stomach and of
      surface columnar epithelia in the colon. However, AQP3 was not apparently
      detected in the small intestine. AQP4 was present on the basolateral membrane of
      the parietal cells in the lower stomach and selectively in the basolateral
      membranes of deep intestinal gland cells in the small intestine. AQP8 mRNA
      expression was demonstrated in the absorptive columnar epithelial cells of the
      jejunum and colon by in situ hybridization. These findings may indicate that
      water crosses the epithelial layer through these water channels, suggesting a
      possible role of the transcellular route for water intake or outlet in the
      gastrointestinal tract.

PMID- 10069990
TI  - Fiber type populations and Ca2+-activation properties of single fibers in soleus
      muscles from SHR and WKY rats.
AB  - Electrophoretic analyses of muscle proteins in whole muscle homogenates and
      single muscle fiber segments were used to examine myosin heavy chain (MHC) and
      myosin light chain 2 (MLC2) isoform composition and fiber type populations in
      soleus muscles from spontaneously hypertensive rats (SHRs) and their age-matched
      normotensive controls [Wistar-Kyoto (WKY) rats], at three stages in the
      development of high blood pressure (4 wk, 16 wk, and 24 wk of age). Demembranated
      (chemically skinned with 2% Triton X-100), single fiber preparations were used to
      determine the maximum Ca2+-activated force per cross-sectional area, calcium
      sensitivity, and degree of cooperativity of the contractile apparatus and Ca2+
      regulatory system with respect to Ca2+. The results show that, at all ages
      examined, 1) SHR soleus contained a lower proportion of MHCI and MLC2 slow
      (MLC2s) and a higher proportion of MHCIIa, MHCIId/x, and MLC2 fast (MLC2f )
      isoforms than the age-matched controls; 2) random dissection of single fibers
      from SHR and WKY soleus produced four populations of fibers: type I (expressing
      MHCI), type IIA (expressing MHCIIa), hybrid type I+IIA (coexpressing MHCI and
      MHCIIa), and hybrid type IIA+IID (coexpressing MHCIIa and MHCIId/x); and 3)
      single fiber dissection from SHR soleus yielded a lower proportion of type I
      fibers, a higher proportion of fast-twitch fibers (types IIA and IIA+IID), and a
      higher proportion of hybrid fibers (types I+IIA and IIA+IID) than the homologous
      muscles from the age-matched WKY rats. Because the presence of hybrid fibers is
      viewed as a marker of muscle transformation, these data suggest that SHR soleus
      undergoes transformation well into adulthood. Our data show also that, for a
      given fiber type, there are no significant differences between SHR and WKY soleus
      muscles with respect to any of the Ca2+-activation properties examined. This
      finding indicates that the lower specific tensions reported in the literature for
      SHR soleus muscles are not due to strain- or hypertension-related differences in
      the function of the contractile apparatus or regulatory system.

PMID- 10069991
TI  - Eosinophil peroxidase increases membrane permeability in mammalian urinary
      bladder epithelium.
AB  - Eosinophil peroxidase (EPO), a cationic protein found in eosinophils, has been
      reported to be cytotoxic independent of its peroxidase activity. This study
      investigated with electrophysiological methods whether EPO is toxic to mammalian
      urinary bladder epithelium. Results indicate that EPO, when added to the mucosal
      solution, increases apical membrane conductance of urinary bladder epithelium
      only when the apical membrane potential is cell interior negative. The EPO
      induced conductance was concentration dependent, with a maximum conductance of
      411 microseconds/cm2 and a Michaelis-Menten constant of 113 nM. The EPO-induced
      conductance was nonselective for K+ and Cl-. The conductance was partially
      reversed using voltage but not by removal of EPO from the bulk solution. Mucosal
      Ca2+ reversed the EPO-induced conductance by a mechanism involving reversible
      block of the conductance. Prolonged exposure (up to 1 h) to EPO was toxic to the
      urinary bladder epithelium, as indicated by an irreversible increase in
      transepithelial conductance. These results suggest that EPO is indeed toxic to
      urinary bladder epithelium via a mechanism that involves an increase in membrane
      permeability.

PMID- 10069992
TI  - Protein kinase C reduces the KCa current of rat tail artery smooth muscle cells.
AB  - The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca
      activated K (KCa) current independently of PKC effects on local Ca release events
      was tested using the patch-clamp technique and freshly isolated rat tail artery
      smooth muscle cells dialyzed with a strongly buffered low-Ca solution. The active
      diacylglycerol analog 1,2-dioctanoyl-sn-glycerol (DOG) at 10 microM attenuated
      the current-voltage (I-V) relationship of the KCa current significantly and
      reduced the KCa current at +70 mV by 70 +/- 4% (n = 14). In contrast, 10 microM
      DOG after pretreatment of the cells with 1 microM calphostin C or 1 microM PKC
      inhibitor peptide, selective PKC inhibitors, and 10 microM 1,3-dioctanoyl-sn
      glycerol, an inactive diacylglycerol analog, did not significantly alter the KCa
      current. Furthermore, the catalytic subunit of PKC (PKCC) at 0.1 U/ml attenuated
      the I-V relationship of the KCa current significantly, reduced the KCa current at
      +70 mV by 44 +/- 3% (n = 17), and inhibited the activity of single KCa channels
      at 0 mV by 79 +/- 9% (n = 6). In contrast, 0.1 U/ml heat-inactivated PKCC did not
      significantly alter the KCa current or the activity of single KCa channels. Thus
      these results suggest that PKC is able to considerably attenuate the KCa current
      of freshly isolated rat tail artery smooth muscle cells independently of effects
      of PKC on local Ca release events, most likely by a direct effect on the KCa
      channel.

PMID- 10069993
TI  - A3 adenosine receptors regulate Cl- channels of nonpigmented ciliary epithelial
      cells.
AB  - Adenosine stimulates Cl- channels of the nonpigmented (NPE) cells of the ciliary
      epithelium. We sought to identify the specific adenosine receptors mediating this
      action. Cl- channel activity in immortalized human (HCE) NPE cells was determined
      by monitoring cell volume in isotonic suspensions with the cationic ionophore
      gramicidin present. The A3-selective agonist N6-(3-iodobenzyl)-adenosine-5'-N
      methyluronamide (IB-MECA) triggered shrinkage (apparent Kd = 55 +/- 10 nM). A3
      selective antagonists blocked IB-MECA-triggered shrinkage, and A3-antagonists
      (MRS-1097, MRS-1191, and MRS-1523) also abolished shrinkage produced by 10 microM
      adenosine when all four known receptor subtypes are occupied. The A1-selective
      agonist N6-cyclopentyladenosine exerted a small effect at 100 nM but not at
      higher or lower concentrations. The A2A agonist CGS-21680 triggered shrinkage
      only at high concentration (3 microM), an effect blocked by MRS-1191. IB-MECA
      increased intracellular Ca2+ in HCE cells and also stimulated short-circuit
      current across rabbit ciliary epithelium. A3 message was detected in both HCE
      cells and rabbit ciliary processes using RT-PCR. We conclude that human HCE cells
      and rabbit ciliary processes possess A3 receptors and that adenosine can activate
      Cl- channels in NPE cells by stimulating these A3 receptors.

PMID- 10069994
TI  - Functional consensus for mammalian osmotic response elements.
AB  - The molecular mechanisms underlying adaptation to hyperosmotic stress through the
      accumulation of organic osmolytes are largely unknown. Yet, among organisms, this
      is an almost universal phenomenon. In mammals, the cells of the renal medulla are
      uniquely exposed to high and variable salt concentrations; in response, renal
      cells accumulate the osmolyte sorbitol through increased transcription of the
      aldose reductase (AR) gene. In cloning the rabbit AR gene, we found the first
      evidence of an osmotic response region in a eukaryotic gene. More recently, we
      functionally defined a minimal essential osmotic response element (ORE) having
      the sequence CGGAAAATCAC(C) (bp -1105 to -1094). In the present study, we
      systematically replaced each base with every other possible nucleotide and tested
      the resulting sequences individually in reporter gene constructs. Additionally,
      we categorized hyperosmotic response by electrophoretic mobility shift assays of
      a 17-bp sequence (-1108 to -1092) containing the native ORE as a probe against
      which the test constructs would compete for binding. In this manner, binding
      activity was assessed for the full range of osmotic responses obtained. Thus we
      have arrived at a functional consensus for the mammalian ORE, NGGAAAWDHMC(N).
      This finding should accelerate the discovery of genes previously unrecognized as
      being osmotically regulated.

PMID- 10069995
TI  - Shrinkage-induced activation of Na+/H+ exchange in rat renal mesangial cells.
AB  - Using the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein
      (BCECF), we examined the effect of hyperosmolar solutions, which presumably
      caused cell shrinkage, on intracellular pH (pHi) regulation in mesangial cells
      (single cells or populations) cultured from the rat kidney. The calibration of
      BCECF is identical in shrunken and unshrunken mesangial cells if the
      extracellular K+ concentration ([K+]) is adjusted to match the predicted
      intracellular [K+]. For pHi values between approximately 6.7 and approximately
      7.4, the intrinsic buffering power in shrunken cells (600 mosmol/kgH2O) is
      threefold larger than in unshrunken cells (approximately 300 mosmol/kgH2O). In
      the nominal absence of CO2/HCO-3, exposing cell populations to a HEPES-buffered
      solution supplemented with approximately 300 mM mannitol (600 mosmol/kgH2O)
      causes steady-state pHi to increase by approximately 0.4. The pHi increase is due
      to activation of Na+/H+ exchange because, in single cells, it is blocked in the
      absence of external Na+ or in the presence of 50 microM ethylisopropylamiloride
      (EIPA). Preincubating cells in a Cl--free solution for at least 14 min inhibits
      the shrinkage-induced pHi increase by 80%. We calculated the pHi dependence of
      the Na+/H+ exchange rate in cell populations under normosmolar and hyperosmolar
      conditions by summing 1) the pHi dependence of the total acid-extrusion rate and
      2) the pHi dependence of the EIPA-insensitive acid-loading rate. Shrinkage alkali
      shifts the pHi dependence of Na+/H+ exchange by approximately 0.7 pH units.

PMID- 10069996
TI  - Polyamine depletion arrests cell cycle and induces inhibitors p21(Waf1/Cip1),
      p27(Kip1), and p53 in IEC-6 cells.
AB  - The polyamines spermidine and spermine and their precursor putrescine are
      intimately involved in and are required for cell growth and proliferation. This
      study examines the mechanism by which polyamines modulate cell growth, cell cycle
      progression, and signal transduction cascades. IEC-6 cells were grown in the
      presence or absence of DL-alpha-difluoromethylornithine (DFMO), a specific
      inhibitor of ornithine decarboxylase, which is the first rate-limiting enzyme for
      polyamine synthesis. Depletion of polyamines inhibited growth and arrested cells
      in the G1 phase of the cell cycle. Cell cycle arrest was accompanied by an
      increase in the level of p53 protein and other cell cycle inhibitors, including
      p21(Waf1/Cip1) and p27(Kip1). Induction of cell cycle inhibitors and p53 did not
      induce apoptosis in IEC-6 cells, unlike many other cell lines. Although polyamine
      depletion decreased the expression of extracellular signal-regulated kinase (ERK)
      2 protein, a sustained increase in ERK-2 isoform activity was observed. The ERK-1
      protein level did not change, but ERK-1 activity was increased in polyamine
      depleted cells. In addition, polyamine depletion induced the stress-activated
      protein kinase/c-Jun NH2-terminal kinase (JNK) type of mitogen-activated protein
      kinase (MAPK). Activation of JNK-1 was the earliest event; within 5 h after DFMO
      treatment, JNK activity was increased by 150%. The above results indicate that
      polyamine depletion causes cell cycle arrest and upregulates cell cycle
      inhibitors and suggest that MAPK and JNK may be involved in the regulation of the
      activity of these molecules.

PMID- 10069997
TI  - Contribution of mitochondrial proton leak to respiration rate in working skeletal
      muscle and liver and to SMR.
AB  - Proton pumping across the mitochondrial inner membrane and proton leak back
      through the natural proton conductance pathway make up a futile cycle that
      dissipates redox energy. We measured respiration and average mitochondrial
      membrane potential in perfused rat hindquarter with maximal tetanic contraction
      of the left gastrocnemius-soleus-plantaris muscle group, and we estimate that the
      mitochondrial proton cycle accounted for 34% of the respiration rate of the
      preparation. Similar measurements in rat hepatocytes given substrates to cause a
      high rate of gluconeogenesis and ureagenesis showed that the proton cycle
      accounted for 22% of the respiration rate of these cells. Combining these in
      vitro values with literature values for the contribution of skeletal muscle and
      liver to standard metabolic rate (SMR), we calculate that the proton cycle in
      working muscle and liver may account for 15% of SMR in vivo. Although this value
      is less than the 20% of SMR we calculated previously using data from resting
      skeletal muscle and hepatocytes, it is still large, and we conclude that the
      futile proton cycle is a major contributor to SMR.

PMID- 10069998
TI  - Chemokine expression in CF epithelia: implications for the role of CFTR in RANTES
      expression.
AB  - To delineate the mechanisms that facilitate leukocyte migration into the cystic
      fibrosis (CF) lung, expression of chemokines, including interleukin-8 (IL-8),
      monocyte chemoattractant protein-1 (MCP-1), and RANTES, was compared between CF
      and non-CF airway epithelia. The findings presented herein demonstrate that,
      under either basal conditions or tumor necrosis factor-alpha (TNF-alpha)- and/or
      interferon-gamma (IFN-gamma)-stimulated conditions, a consistent pattern of
      differences in the secretion of IL-8 and MCP-1 between CF and non-CF epithelial
      cells was not observed. In contrast, CF epithelial cells expressed no detectable
      RANTES protein or mRNA under basal conditions or when stimulated with TNF-alpha
      and/or IFN-gamma (P </= 0.05), unlike their non-CF counterparts. Correction of
      the CF transmembrane conductance regulator (CFTR) defect in CF airway epithelial
      cells restored the induction of RANTES protein and mRNA by TNF-alpha in
      combination with IFN-gamma (P </= 0.05) but had little effect on IL-8 or MCP-1
      production compared with mock controls. Transfection studies utilizing RANTES
      promoter constructs suggested that CFTR activates the RANTES promoter via a
      nuclear factor-kappaB-mediated pathway. Together, these results suggest that 1)
      RANTES expression is altered in CF epithelia and 2) epithelial expression of
      RANTES, but not IL-8 or MCP-1, is dependent on CFTR.

PMID- 10069999
TI  - Incubation of OKP cells in low-K+ media increases NHE3 activity after early
      decrease in intracellular pH.
AB  - Chronic hypokalemia increases the activity of proximal tubule apical membrane
      Na+/H+ antiporter NHE3. The present study examined the effect of the incubation
      of OKP cells (an opossum kidney, clone P cell line) in control medium (K+ concn
      ([K+]) = 5.4 mM) or low-K+ medium ([K+] = 2.7 mM) on NHE3. The activity of an
      ethylisopropyl amiloride-resistant Na+/H+ antiporter, whose characteristics were
      consistent with those of NHE3, was increased in low-K+ cells beginning at 8 h.
      NHE3 mRNA and NHE3 protein abundance were increased 2.2-fold and 62%,
      respectively, at 24 h but not at 8 h. After incubation in low-K+ medium,
      intracellular pH (pHi) decreased by 0.27 pH units (maximum at 27 min) and then
      recovered to the control level. Intracellular acidosis induced by 5 mM sodium
      propionate increased Na+/H+ antiporter activity at 8 and 24 h. Herbimycin A, a
      tyrosine kinase inhibitor, blocked low-K+- and sodium propionate-induced
      activation of the Na+/H+ antiporter at 8 and 24 h. Our results demonstrate that
      low-K+ medium causes an early decrease in pHi, which leads to an increase in NHE3
      activity via a tyrosine kinase pathway.

PMID- 10070000
TI  - Monocytic cell necrosis is mediated by potassium depletion and caspase-like
      proteases.
AB  - Apoptosis is a physiological cell death that culminates in mitochondrial
      permeability transition and the activation of caspases, a family of cysteine
      proteases. Necrosis, in contrast, is a pathological cell death characterized by
      swelling of the cytoplasm and mitochondria and rapid plasma membrane disruption.
      Necrotic cell death has long been opposed to apoptosis, but it now appears that
      both pathways involve mitochondrial permeability transition, raising the question
      of what mediates necrotic cell death. In this study, we investigated mechanisms
      that promote necrosis induced by various stimuli (Clostridium difficile toxins,
      Staphylococcus aureus alpha toxin, ouabain, nigericin) in THP-1 cells, a human
      monocytic cell line, and in monocytes. All stimuli induced typical features of
      necrosis and triggered protease-mediated release of interleukin-1beta (IL-1beta)
      and CD14 in both cell types. K+ depletion was actively implicated in necrosis
      because substituting K+ for Na+ in the extracellular medium prevented
      morphological features of necrosis and IL-1beta release. N-benzyloxycarbonyl-Val
      Ala-Asp-fluoromethyl ketone, a broad-spectrum caspase inhibitor, prevented
      morphological features of necrosis, plasma membrane destruction, loss of
      mitochondrial membrane potential, IL-1beta release, and CD14 shedding induced by
      all stimuli. Thus, in monocytic cells, necrosis is a cell death pathway mediated
      by passive K+ efflux and activation of caspase-like proteases.

PMID- 10070001
TI  - Enhancement of endocytosis due to aminophospholipid transport across the plasma
      membrane of living cells.
AB  - Formation of intracellular vesicles is initiated by membrane budding. Here we
      test the hypothesis that the plasma membrane surface area asymmetry could be a
      driving force for vesicle formation during endocytosis. The inner layer
      phospholipid number was therefore increased by adding exogenous
      aminophospholipids to living cells, which were then translocated from the outer
      to the inner layer of the membrane by the ubiquitous flippase. Addition of either
      phosphatidylserine or phosphatidylethanolamine led to an enhancement of
      endocytosis, showing that the observed acceleration does not depend on the lipid
      polar head group. Conversely, a closely related aminophospholipid that is not
      recognized by the flippase, lyso-alpha-phosphatidylserine, inhibited endocytosis,
      and similar results were obtained with a cholesterol derivative that also remains
      in the plasma membrane outer layer. Thus an increase of lipid concentration in
      the inner layer enhanced internalization, whereas an increase of the lipid
      concentration in the outer layer inhibited internalization. These experiments
      suggest that transient asymmetries in lipid concentration might contribute to the
      formation of endocytic vesicles.

PMID- 10070002
TI  - EGF precursor mRNA and membrane-associated EGF precursor protein in rat exorbital
      lacrimal gland.
AB  - This study was designed to demonstrate the presence of epidermal growth factor
      (EGF) in the rat exorbital lacrimal gland. EGF precursor gene transcription was
      demonstrated first by RT-PCR analysis of lacrimal gland RNA using a set of
      specific primers and second by Northern blot analysis of rat lacrimal gland mRNA.
      A rabbit polyclonal antibody (rEGF2) directed against rat submaxillary gland EGF
      was used to detect EGF-containing proteins by RIA. Results indicate that the rat
      lacrimal gland does not contain detectable soluble and mature EGF but that the
      EGF immunoreactivity is associated with the membrane-enriched fraction. Analysis
      of the detergent-solubilized membrane proteins by gel filtration shows that
      membrane-associated EGF immunoreactivity was present as a high-molecular-mass
      protein. Moreover, as shown by Western blot analysis, a specific anti-rat EGF
      precursor antibody (ppEGF1) can immunoprecipitate a 152-kDa EGF-containing
      protein. Taken together, these results demonstrate for the first time both EGF
      precursor gene transcription and EGF precursor protein expression in a lacrimal
      tissue, i.e., the rat exorbital lacrimal gland. The demonstration that EGF
      appears to be stored only as its full-length membrane precursor may provide
      important information to study the regulation of its secretory process.

PMID- 10070003
TI  - Synthesis and characterization of dual-wavelength Cl--sensitive fluorescent
      indicators for ratio imaging.
AB  - The fluorescence of quinolinium-based Cl- indicators such as 6-methoxy-N-(3
      sulfopropyl)quinolinium (SPQ) is quenched by Cl- by a collisional mechanism
      without change in spectral shape. A series of "chimeric" dual-wavelength Cl-
      indicators were synthesized by conjugating Cl--sensitive and -insensitive
      chromophores with spacers. The SPQ chromophore (N-substituted 6
      methoxyquinolinium; MQ) was selected as the Cl--sensitive moiety [excitation
      wavelength (lambdaex) 350 nm, emission wavelength (lambdaem) 450 nm]. N
      substituted 6-aminoquinolinium (AQ) was chosen as the Cl--insensitive moiety
      because of its different spectral characteristics (lambdaex 380 nm, lambdaem 546
      nm), insensitivity to Cl-, positive charge (to minimize quenching by chromophore
      stacking/electron transfer), and reducibility (for noninvasive cell loading). The
      dual-wavelength indicators were stable and nontoxic in cells and were distributed
      uniformly in cytoplasm, with occasional staining of the nucleus. The brightest
      and most Cl--sensitive indicators were alpha-MQ-alpha'-dimethyl-AQ-xylene
      dichloride and trans-1, 2-bis(4-[1-alpha'-MQ-1'-alpha'-dimethyl-AQ-xylyl]
      pyridinium)ethyl ene (bis-DMXPQ). At 365-nm excitation, emission maxima were at
      450 nm (Cl- sensitive; Stern-Volmer constants 82 and 98 M-1) and 565 nm (Cl-
      insensitive). Cystic fibrosis transmembrane conductance regulator-expressing
      Swiss 3T3 fibroblasts were labeled with bis-DMXPQ by hypotonic shock or were
      labeled with its uncharged reduced form (octahydro-bis-DMXPQ) by brief incubation
      (20 microM, 10 min). Changes in Cl- concentration in response to Cl-/nitrate
      exchange were recorded by emission ratio imaging (450/565 nm) at 365-nm
      excitation wavelength. These results establish a first-generation set of chimeric
      bisquinolinium Cl- indicators for ratiometric measurement of Cl- concentration.

PMID- 10070004
TI  - Effect of acidification on the location of H+-ATPase in cultured inner medullary
      collecting duct cells.
AB  - In previous studies, our laboratory has utilized a cell line derived from the rat
      inner medullary collecting duct (IMCD) as a model system for mammalian renal
      epithelial cell acid secretion. We have provided evidence, from a physiological
      perspective, that acute cellular acidification stimulates apical exocytosis and
      elicits a rapid increase in proton secretion that is mediated by an H+-ATPase.
      The purpose of these experiments was to examine the effect of acute cellular
      acidification on the distribution of the vacuolar H+-ATPase in IMCD cells in
      vitro. We utilized the 31-kDa subunit of the H+-ATPase as a marker of the
      complete enzyme. The distribution of this subunit of the H+-ATPase was evaluated
      by immunohistochemical techniques (confocal and electron microscopy), and we
      found that there is a redistribution of these pumps from vesicles to the apical
      membrane. Immunoblot evaluation of isolated apical membrane revealed a 237 +/-
      34% (P < 0.05, n = 9) increase in the 31-kDa subunit present in the membrane
      fraction 20 min after the induction of cellular acidification. Thus our results
      demonstrate the presence of this pump subunit in the IMCD cell line in vitro and
      that cell acidification regulates the shuttling of cytosolic vesicles containing
      the 31-kDa subunit into the apical membrane.

PMID- 10070005
TI  - Whole body glucose metabolism.
AB  - This review describes major factors that, singly or together, influence the
      concentration and distribution of D-glucose in mammals, particularly in humans,
      with emphasis on rest, physical activity, and alimentation. It identifies areas
      of uncertainty: distribution and concentrations of glucose in interstitial fluid,
      kinetics and mechanism of transcapillary glucose transport, kinetics and
      mechanism of glucose transport via its transporters into cells, detailed
      mechanisms by which hormones, exercise, and hypoxia affect glucose movement
      across cell membranes, whether translocation of glucose transporters to the cell
      membrane accounts completely, or even mainly, for insulin-stimulated glucose
      uptake, whether exercise stimulates release of a circulating insulinomimetic
      factor, and the relation between muscle glucose uptake and muscle blood flow. The
      review points out that there is no compartment of glucose in the body at which
      all glucose is at the same concentration, and that models of glucose metabolism,
      including effects of insulin on glucose metabolism based on assumptions of
      concentration homogeneity, cannot be entirely correct. A fresh approach to
      modeling is needed.

PMID- 10070006
TI  - Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid
      metabolism.
AB  - The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic,
      and leg fatty acid metabolism were determined in five volunteers. Catheters were
      placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids
      were infused, once in the basal state and, on a different occasion, during
      infusion of dextrose (clamp; arterial glucose 8.8 +/- 0.5 mmol/l). Lipids and
      heparin were infused together with the dextrose to maintain plasma fatty acid
      concentrations at basal levels. Fatty acid availability in plasma and fatty acid
      uptake across the splanchnic region and the leg were similar during the basal and
      clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8%
      (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty
      acid uptake oxidized decreased at the whole body level (53 to 29%), across the
      splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We
      conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits
      fatty acid oxidation to a similar extent at the whole body level, across the leg,
      and across the splanchnic region, even when fatty acid availability is constant.

PMID- 10070007
TI  - Decreased hexosamine biosynthesis in GH-deficient dwarf rat muscle. reversal with
      GH, but not IGF-I, therapy.
AB  - Enhanced glucose flux via the hexosamine biosynthesis pathway (HNSP) has been
      implicated in insulin resistance. We measured L-glutamine:D-fructose-6-phosphate
      amidotransferase activity (GFAT, a rate-limiting enzyme) and concentrations of
      UDP-N-acetyl hexosamines (UDP-HexNAc, major products of HNSP) in muscle and liver
      of growth hormone (GH)-deficient male dwarf (dw) rats. All parameters measured,
      except body weight, were similar in 5-wk-old control and dw rats. Muscle GFAT
      activity declined progressively with age in controls and dw rats but was
      consistently 30-60% lower in 8- to 14-wk-old dw rats vs. age-matched controls;
      UDP-HexNAc concentrations in muscle were concomitantly 30% lower in dw rats vs.
      controls (P < 0.01). Concentrations of UDP-hexoses, GDP-mannose, and UDP in
      muscle were similar in control and dw rats. Muscle HNSP activity was similarly
      diminished in fed and fasted dw rats. In liver, only a small difference in GFAT
      activity was evident between controls and dw rats, and no differences in UDP
      HexNAc concentrations were observed. Treatment with recombinant human GH (rhGH)
      for 5 days restored UDP-HexNAc to control levels in dw muscles (P < 0.01) and
      partially restored GFAT activity. Insulin-like growth factor I treatment was
      ineffective. We conclude that GH participates in HNSP regulation in muscle.

PMID- 10070008
TI  - Effect of leptin deficiency on metabolic rate in ob/ob mice.
AB  - Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob)
      mice; however, available studies have been criticized for referencing O2
      consumption (VO2) to estimated rather than true lean body mass. To evaluate
      whether leptin deficiency reduces energy expenditure, four separate experiments
      were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass,
      permitting VO2 to be referenced to true nonfat mass; 2) dietary manipulation was
      used in an attempt to eliminate differences in body weight and composition
      between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3
      mg. kg-1. day-1) on VO2 were examined; and 4) body weight and composition were
      compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater
      mass, less lean body mass, and a 10% higher metabolic rate when VO2 was
      referenced to lean mass. Dietary manipulation achieved identical body weight in
      ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals,
      percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin
      increased VO2 in ob/ob but not control animals. Weight loss in leptin-repleted
      ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the
      basis of the observed increase in VO2 and accelerated weight loss seen with
      leptin repletion, that leptin deficiency causes a reduction in metabolic rate in
      ob/ob mice. In contrast, these physiological studies suggest that comparison of
      VO2 in obese and lean animals does not produce useful information on the
      contribution of leptin to metabolism.

PMID- 10070009
TI  - Isolation and characterization of plasmin-generated bioactive fragments of IGFBP
      3.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) was digested with plasmin,
      and the proteolytic fragments were isolated by HPLC and tested for bioactivity as
      measured by stimulation of glucose uptake in microvessel endothelial cells. Two
      of the pooled fractions of the digest stimulated glucose uptake. The major
      bioactive pool, at an estimated protein concentration <50 ng/ml, stimulated
      glucose uptake to 150% of control with greater stimulation and 220% of control at
      approximately 250 ng/ml. Two fragments were present in the bioactive fraction,
      the dominant one migrating at approximately 20,000 and the other at approximately
      8,000. Both fragments bound 125I-labeled insulin-like growth factor and
      [3H]heparin. NH2-terminal amino acid analysis of the bioactive peak yielded two
      sequences. One, representing the majority of the material, had an NH2-terminal
      sequence identical to IGFBP-3; the second fragment began at amino acid 202 of
      IGFBP-3. In contrast to the bioactive fragments, intact IGFBP-3, at
      concentrations up to 130 microgram/ml, had no bioactivity. These findings
      demonstrate that IGFBP-3 can be degraded into fragments that have potent
      bioactivities that are not present in the intact IGFBP-3 molecule.

PMID- 10070010
TI  - Endotoxin-induced changes in IGF-I differ in rats provided enteral vs. parenteral
      nutrition.
AB  - The purpose of the present study was to determine whether acute changes in the
      insulin-like growth factor (IGF) system induced by mild surgical trauma/fasting
      or endotoxin [lipopolysaccharide (LPS)] are differentially modulated by total
      enteral nutrition (TEN) or total parenteral nutrition (TPN). Rats had vascular
      catheters and a gastrostomy tube surgically placed and were fasted overnight. The
      next morning animals randomly received an isocaloric, isonitrogenous (250 kcal.
      kg-1. day-1, 1.6 g N. kg-1. day-1) infusion of either TEN or TPN for 48 h. Then
      rats were injected intravenously with Escherichia coli LPS (1 mg/kg) while
      nutritional support was continued. Time-matched control animals were injected
      with saline. After mild surgical trauma and an 18-h fast, TEN was more effective
      at increasing plasma IGF-I levels than TPN. Subsequent injection of LPS decreased
      IGF-I in blood, liver, and muscle in both TEN- and TPN-fed rats compared with
      saline-injected control animals. However, this decrease was approximately 30%
      greater in rats fed TPN compared with those fed TEN. LPS-induced downregulation
      of IGF-I mRNA expression in liver and muscle was also more prominent in TPN-fed
      rats. The LPS-induced increase in plasma corticosterone and tumor necrosis factor
      alpha was greater (2- and 1.6-fold, respectively) in TPN-fed rats, and these
      changes were consistent with the greater reduction in IGF-I seen in these
      animals. In similarly treated rats allowed to survive for 24 h after LPS
      injection, the LPS-induced increase in the urinary 3-methylhistidine-to
      creatinine ratio was smaller in TEN-fed rats. In summary, LPS reduced systemic
      levels of IGF-I as well as IGF-I protein and mRNA in critical target organs.
      Enteral feeding greatly attenuated this response. Maintenance of higher IGF-I
      levels in TEN-fed rats was associated with a reduction in inflammatory cytokine
      levels and lower rates of myofibrillar degradation.

PMID- 10070011
TI  - Leukemia inhibitory factor and oncostatin M stimulate collagenase-3 expression in
      osteoblasts.
AB  - Leukemia inhibitory factor (LIF) and oncostatin M (OSM) have multiple effects on
      skeletal remodeling. Although these cytokines modestly regulate collagen
      synthesis in osteoblasts, their effects on collagenase expression and collagen
      degradation are not known. We tested whether LIF and OSM regulate the expression
      of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs) in osteoblast-enriched cells isolated from fetal rat calvariae. LIF and
      OSM increased collagenase-3 (MMP-13) mRNA and immunoreactive protein levels in a
      time- and dose-dependent manner. LIF and OSM enhanced the rate of transcription
      of the collagenase gene and stabilized collagenase mRNA in transcriptionally
      arrested cells. LIF and OSM failed to regulate the expression of gelatinase A
      (MMP-2) and B (MMP-9). LIF and OSM modestly stimulated the expression of TIMP-1
      but did not alter the expression of TIMP-2 and -3. In conclusion, LIF and OSM
      stimulate collagenase-3 and TIMP-1 expression in osteoblasts, and these effects
      may be involved in mediating the bone remodeling actions of these cytokines.

PMID- 10070012
TI  - The importance of pyruvate availability to PDC activation and anaplerosis in
      human skeletal muscle.
AB  - No studies have singularly investigated the relationship between pyruvate
      availability, pyruvate dehydrogenase complex (PDC) activation, and anaplerosis in
      skeletal muscle. This is surprising given the functional importance attributed to
      these processes in normal and disease states. We investigated the effects of
      changing pyruvate availability with dichloroacetate (DCA), epinephrine, and
      pyruvate infusions on PDC activation and accumulation of acetyl groups and
      tricarboxylic acid (TCA) cycle intermediates (TCAI) in human muscle. DCA
      increased resting PDC activity sixfold (P < 0.05) but decreased the muscle TCAI
      pool (mmol/kg dry muscle) from 1.174 +/- 0.042 to 0.747 +/- 0.055 (P < 0.05).
      This was probably a result of pyruvate being diverted to acetyl-CoA and
      acetylcarnitine after near-maximal activation of PDC by DCA. Conversely, neither
      epinephrine nor pyruvate activated PDC. However, both increased the TCAI pool
      (1.128 +/- 0.076 to 1.614 +/- 0.188, P < 0.05 and 1.098 +/- 0.059 to 1.385 +/-
      0.114, P < 0.05, respectively) by providing a readily available pool of pyruvate
      for anaplerosis. These data support the hypothesis that TCAI pool expansion is
      principally a reflection of increased muscle pyruvate availability and, together
      with our previous work (J. A. Timmons, S. M. Poucher, D. Constantin-Teodosiu, V.
      Worrall, I. A. Macdonald, and P. L. Greenhaff. J. Clin. Invest. 97: 879-883,
      1996), indicate that TCA cycle expansion may be of little functional significance
      to TCA cycle flux. It would appear therefore that the primary effect of DCA on
      oxidative ATP provision is to provide a readily available pool of acetyl groups
      to the TCA cycle at the onset of exercise rather than increasing TCA cycle flux
      by expanding the TCAI pool.

PMID- 10070013
TI  - Nonsaturable entry of neuropeptide Y into brain.
AB  - Neuropeptide Y (NPY) is found and is active both in the periphery and brain, but
      its crossing of the blood-brain barrier (BBB) in either direction has not been
      measured. We used multiple time-regression analysis to determine that
      radioactively labeled NPY injected intravenously entered the brain much faster
      than albumin, with an influx constant of 2.0 x 10(-4) ml. g. -1. min-1. However,
      this rate of entry was not significantly changed by injection of 10
      microgram/mouse of excess NPY, by leptin, or by food deprivation. HPLC showed
      that most of the NPY entering the brain was intact, and capillary depletion with
      and without washout showed that the NPY did not remain bound to endothelial cells
      or associated with vascular elements. Perfusion in a blood-free solution
      eliminated binding to serum proteins as an explanation for the lack of
      saturation. Efflux of labeled NPY from the brain occurred at the same rate as
      albumin, reflecting the normal rate of reabsorption of cerebrospinal fluid. Thus
      NPY can readily enter the brain from blood by diffusion across the BBB.

PMID- 10070014
TI  - Pyruvate dehydrogenase activation in inactive muscle during and after maximal
      exercise in men.
AB  - Pyruvate dehydrogenase activity (PDHa) and acetyl-group accumulation were
      examined in the inactive deltoid muscle in response to maximal leg exercise in
      men. Seven subjects completed three consecutive 30-s bouts of maximal isokinetic
      cycling, with 4-min rest intervals between bouts. Biopsies of the deltoid were
      obtained before exercise, after bouts 1 and 3, and after 15 min of rest recovery.
      Inactive muscle lactate (LA) and pyruvate (PYR) contents increased more than
      twofold (P < 0.05) after exercise (bout 3) and remained elevated after 15 min of
      recovery (P < 0.05). Increased PYR accumulation secondary to LA uptake by the
      inactive deltoid was associated with greater PDHa, which progressively increased
      from 0.71 +/- 0.23 mmol. min-1. kg wet wt-1 at rest to a maximum of 1.83 +/- 0.30
      mmol. min-1. kg wet wt-1 after bout 3 (P < 0.05) and remained elevated after 15
      min of recovery (1.63 +/- 0.24 mmol. min-1. kg wet wt-1; P < 0.05). Acetyl-CoA
      and acetylcarnitine accumulations were unaltered. Increased PDHa allowed and did
      not limit the oxidation of LA and PYR in inactive human skeletal muscle after
      maximal exercise.

PMID- 10070015
TI  - High-resistance training and muscle metabolism during prolonged exercise.
AB  - To investigate the hypothesis that changes in muscle submaximal exercise
      metabolism would occur as a result of fiber hypertrophy, induced by high
      resistance training (HRT), active but untrained males (age 20 +/- 0.7 yr; mean +/
      SE) performed lower-limb weight training 3 days/wk for 12 wk using three sets of
      6-8 repetitions maximal (RM)/day. Muscle metabolism was examined at different
      stages of training (4, 7, and 12 wk) using a two-stage continuous cycle test
      performed at the same absolute power output and duration (56.4 +/- 2.9 min) and
      representing 57 and 72% of pretraining peak aerobic power (VO2 peak). Compared
      with pretraining, at the end of exercise, HRT resulted in a higher (P < 0.05)
      phosphocreatine (PCr; 27.4 +/- 6. 7 vs. 38.0 +/- 1.9 mmol/kg dry wt), a lower
      lactate (38.9 +/- 8.5 vs. 24.4 +/- 6.1 mmol/kg dry wt), and a higher (P < 0.05)
      glycogen content (132 +/- 11 vs. 181 +/- 7.5 mmol glucosyl units/kg dry wt). The
      percent change from rest before and after training was 63 and 50% for PCr, 676
      and 410% for lactate, and 60 and 43% for glycogen, respectively. These
      adaptations, which were observed only at 72% VO2 peak, occurred by 4 wk of
      training in the case of PCr and glycogen and before any changes in fiber cross
      sectional area, capillarization, or oxidative potential. Fiber hypertrophy,
      observed at 7 and 12 wk of training, failed to potentiate the metabolic response.
      No effect of HRT was found on VO2 peak with training (41.2 +/- 2.9 vs. 41.0 +/-
      2.1 ml. kg-1. min-1) or on the steady-state, submaximal exercise rate of oxygen
      consumption. It is concluded that the HRT results in muscle metabolic adaptations
      that occur independently of fiber hypertrophy.

PMID- 10070016
TI  - Kinetics of dodecanedioic acid triglyceride in rats.
AB  - The kinetics of the triglyceride of dodecanedioic acid (TGDA) has been
      investigated in 30 male Wistar rats after a rapid intravenous bolus injection.
      TGDA and its product of hydrolysis, nonesterified dodecanedioic acid (NEDA), were
      measured in plasma samples taken at different times using an improved high
      performance liquid chromatographic method. The 24-h urinary excretion of TGDA was
      1.54 +/- 0.37 micromol, corresponding to approximately 0.67% of the administered
      amount. Several kinetics models were considered, including central and peripheral
      compartments for the triglyceride and the free forms and expressing transports
      between compartments with combinations of linear, carrier-limited, or time
      varying mechanisms. The parameter estimates of the kinetics of TGDA and of NEDA
      were finally obtained using a three-compartment model in which the transfer of
      TGDA to NEDA was assumed to be linear, through a peripheral compartment, and the
      tissue uptake of NEDA was assumed to be carrier limited. TGDA had a large volume
      of distribution ( approximately 0.5 l/kg body wt) with a fast disappearance rate
      from plasma (0.42 min-1), whereas NEDA had a very small volume of distribution (
      approximately 0.04 l/kg body wt) and a tissue uptake with maximal transport rate
      of 0.636 mM/min. In conclusion, this first study on the triglyceride form of
      dodecanedioic acid indicates that it is rapidly hydrolyzed and that both
      triglyceride and nonesterified forms are excreted in the urine to a very low
      extent. The tissue uptake rate of NEDA is consistent with the possibility of
      achieving substantial energy delivery, should it be added to parenteral nutrition
      formulations. Furthermore, the amount of sodium administered with the
      triglyceride form is one-half of that necessary with the free diacid.

PMID- 10070017
TI  - Contribution of protein kinase C to ET-1-induced proliferation in human
      myometrial cells.
AB  - The role of protein kinase C (PKC) in endothelin-1 (ET-1)-induced proliferation
      of human myometrial cells was investigated. ET-1 dose dependently stimulated DNA
      synthesis and the number of cultured myometrial cells. Inhibition of PKC by
      calphostin C or Ro-31-8220 or downregulation of PKC eliminated the proliferative
      effects of ET-1. The failure of two protein tyrosine kinase (PTK) inhibitors
      (tyrphostin 51 and tyrphostin 23) to affect ET-1-induced proliferation supports
      the hypothesis of noninvolvement of the tyrosine kinase signaling pathway in this
      process. The expression and distribution of PKC isoforms were examined by Western
      blot analysis. The five PKC isoforms (PKC-alpha, -beta1, -beta2, -zeta, -epsilon)
      evidenced in human myometrial tissue were found to be differentially expressed in
      myometrial cells, with a predominant expression of PKC-alpha and PKC-zeta.
      Treatment with phorbol 12, 13-dibutyrate (PDBu) resulted in the translocation of
      all five isoforms to the particulate fraction, whereas ET-1 induced a selective
      increase in particulate PKC-beta1, PKC-beta2, and PKC-epsilon. Our findings that
      multiple PKC isoforms are differentially responsive to ET-1 or PDBu suggest that
      they play distinct roles in the myometrial growth process.

PMID- 10070018
TI  - Voltage-dependent entry and generation of slow Ca2+ oscillations in glucose
      stimulated pancreatic beta-cells.
AB  - The role of voltage-dependent Ca2+ entry for glucose generation of slow
      oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) was evaluated in
      individual mouse pancreatic beta-cells. Like depolarization with K+, a rise of
      the glucose concentration resulted in an enhanced influx of Mn2+, which was
      inhibited by nifedipine. This antagonist of L-type Ca2+ channels also blocked the
      slow oscillations of [Ca2+]i induced by glucose. The slow oscillations occurred
      in synchrony with variations in Mn2+ influx and bursts of action currents, with
      the elevation of [Ca2+]i being proportional to the frequency of the action
      currents. A similar relationship was obtained when Ca2+ was replaced with Sr2+.
      Occasionally, the slow [Ca2+]i oscillations were superimposed with pronounced
      spikes temporarily arresting the action currents. It is concluded that the
      glucose-induced slow oscillations of [Ca2+]i are caused by periodic
      depolarization with Ca2+ influx through L-type channels. Ca2+ spiking, due to
      intracellular mobilization, may be important for chopping the slow oscillations
      of [Ca2+]i into shorter ones characterizing beta-cells situated in pancreatic
      islets.

PMID- 10070019
TI  - Sympathetic nervous system activity and alpha-adrenergic responsiveness in older
      hypertensive humans.
AB  - We have previously demonstrated in normotensive humans an age-associated increase
      in sympathetic nervous system (SNS) activity combined with appropriate
      downregulation of alpha-adrenergic responsiveness. Impaired downregulation of
      alpha-adrenergic responsiveness, despite a comparable level of SNS activity,
      could contribute to higher blood pressure in older hypertensive humans. We
      measured arterial plasma norepinephrine (NE) levels and the extravascular NE
      release rate (NE2) derived from [3H]NE kinetics (to assess systemic SNS
      activity), and platelet and forearm arterial adrenergic responsiveness in 20
      normotensive (N) and in 24 hypertensive (H), otherwise healthy, older subjects
      (60-75 yr). Although plasma NE levels were similar (N 357 +/- 27 vs. H 322 +/- 22
      pg/ml; P = 0.37), NE2 tended to be greater in the hypertensive group (H 2.23 +/-
      0.21 vs. N 1.64 +/- 0.20 microgram. min-1. m-2; P = 0. 11), and the NE metabolic
      clearance rate was greater (H 1,100 +/- 30 vs. N 900 +/- 50 ml/m2; P = 0.004). In
      the hypertensive group, there was a greater alpha-agonist-mediated inhibition of
      platelet membrane adenylyl cyclase activity and a NE- but not ANG II-mediated
      decrease in forearm blood flow. Compared with normotensive subjects, in older
      hypertensive subjects 1) NE metabolic clearance rate is increased, 2) systemic
      SNS activity tends to be increased, and 3) arterial and platelet alpha-adrenergic
      responsiveness is enhanced. These results suggest that heightened SNS activity
      coupled with enhanced alpha-adrenergic responsiveness may contribute to elevated
      blood pressure in older hypertensive humans.

PMID- 10070020
TI  - Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose
      production in cirrhosis.
AB  - Net hepatic glycogenolysis and gluconeogenesis were examined in normal (n = 4)
      and cirrhotic (n = 8) subjects using two independent methods [13C nuclear
      magnetic resonance spectroscopy (NMR) and a 2H2O method]. Rates of net hepatic
      glycogenolysis were calculated by the change in hepatic glycogen content before (
      approximately 11:00 PM) and after ( approximately 7:00 AM) an overnight fast
      using 13C NMR and magnetic resonance imaging. Gluconeogenesis was calculated as
      the difference between the rates of glucose production determined with an
      infusion of [6,6-2H2]glucose and net hepatic glycogenolysis. In addition, the
      contribution of gluconeogenesis to glucose production was determined by the 2H
      enrichment in C-5/C-2 of blood glucose after intake of 2H2O (5 ml/kg body water).
      Plasma levels of total and free insulin-like growth factor I (IGF-I) and IGF-I
      binding proteins-1 and -3 were significantly decreased in the cirrhotic subjects
      (P < 0.01 vs. controls). Postprandial hepatic glycogen concentrations were 34%
      lower in the cirrhotic subjects (P = 0.007). Rates of glucose production were
      similar between the cirrhotic and healthy subjects [9.0 +/- 0.9 and 10.0 +/- 0.8
      micromol. kg body wt-1. min-1, respectively]. Net hepatic glycogenolysis was 3.5
      fold lower in the cirrhotic subjects (P = 0.01) and accounted for only 13 +/- 6%
      of glucose production compared with 40 +/- 10% (P = 0.03) in the control
      subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and
      accounted for 87 +/- 6% of glucose production vs. controls: 60 +/- 10% (P =
      0.03). Gluconeogenesis in the cirrhotic subjects, as determined from the 2H
      enrichment in glucose C-5/C-2, was also increased and accounted for 68 +/- 3% of
      glucose production compared with 54 +/- 2% (P = 0.02) in the control subjects. In
      conclusion, cirrhotic subjects have increased rates of gluconeogenesis and
      decreased rates of net hepatic glycogenolysis compared with control subjects.
      These alterations are likely important contributing factors to their altered
      carbohydrate metabolism.

PMID- 10070021
TI  - HaCaT human keratinocytes express IGF-II, IGFBP-6, and an acid-activated protease
      with activity against IGFBP-6.
AB  - The insulin-like growth factor (IGF) system plays an important role in skin.
      HaCaT human keratinocytes proliferate in response to IGFs and synthesize IGF
      binding protein-3 (IGFBP-3). Recently, IGFBP-6 was also identified by NH2
      terminal sequencing, but it has not been identified by Western ligand blotting.
      In the present study, IGFBP-6 was detected in HaCaT-conditioned medium by use of
      immunoblotting and Western ligand blotting with 125I-labeled IGF-II. Proteolytic
      activity against IGFBPs, an important mechanism for regulation of their activity,
      was then studied. An acid-activated, cathepsin D-like protease that cleaved both
      IGFBP-6 and IGFBP-3 was detected. Although proteolysis did not substantially
      reduce the size of immunoreactive IGFBP-6, it greatly reduced the ability of
      IGFBP-6 to bind 125I-IGF-II as determined by Western ligand blotting and solution
      assay. HaCaT keratinocytes do not express IGF-I mRNA, but IGF-II mRNA and protein
      expression was detected. These observations suggest the possibility of an
      autocrine IGF-II loop that is regulated by the relative expression of IGF-II,
      IGFBP-3, and IGFBP-6, and IGFBP proteases in these keratinocytes, although
      demonstration of this loop requires further study.

PMID- 10070022
TI  - Effect of fast duration on disposition of an intraduodenal glucose load in the
      conscious dog.
AB  - The effects of prior fast duration (18 h, n = 8; 42 h, n = 8) on the glycemic and
      tissue-specific responses to an intraduodenal glucose load were studied in
      chronically catheterized conscious dogs. [3-3H]glucose was infused throughout the
      study. After basal measurements, glucose spiked with [U-14C]glucose was infused
      for 150 min intraduodenally. Arterial insulin and glucagon were similar in the
      two groups. Arterial glucose (mg/dl) rose approximately 70% more during glucose
      infusion after 42 h than after an 18-h fast. The net hepatic glucose balance (mg.
      kg-1. min-1) was similar in the two groups (basal: 1.8 +/- 0.2 and 2.0 +/- 0.3;
      glucose infusion: -2.2 +/- 0.5 and -2.2 +/- 0.7). The intrahepatic fate of
      glucose was 79% glycogen, 13% oxidized, and 8% lactate release after a 42-h fast;
      it was 23% glycogen, 21% oxidized, and 56% lactate release after an 18-h fast.
      Net hindlimb glucose uptake was similar between groups. The appearance of
      intraduodenal glucose during glucose infusion (mg/kg) was 900 +/- 50 and 1,120 +/
      40 after 18- and 42-h fasts (P < 0.01). CONCLUSION: glucose administration after
      prolonged fasting induces higher circulating glucose than a shorter fast
      (increased appearance of intraduodenal glucose); liver and hindlimb glucose
      uptakes and the hormonal response, however, are unchanged; finally, an
      intrahepatic redistribution of carbons favors glycogen deposition.

PMID- 10070023
TI  - Comparison of the LDL-receptor binding of VLDL and LDL from apoE4 and apoE3
      homozygotes.
AB  - Compared with apolipoprotein E3 (apoE3), apoE2 is less effective in mediating the
      binding of lipoproteins to the low-density lipoprotein (LDL) receptor. The
      influence of the E4 isoform, which is associated with adverse effects on plasma
      lipids and coronary heart disease, is less clear. We compared the ability of very
      low density lipoprotein (VLDL) and LDL from paired E4/4 and E3/3 subjects to
      compete against 125I-labeled LDL for binding with the LDL receptor on cultured
      fibroblasts and Hep G2 cells. The concentrations of VLDL or LDL required to
      inhibit binding of 125I-LDL by 50% (IC50, microgram apoB/ml) were determined, and
      results were assessed in terms of an IC50 ratio, E4/4 IC50 relative to E3/3 IC50,
      to reduce the influence of interassay variability. In Hep G2 cells, E4/4 VLDL was
      more effective than E3/3 VLDL in competing for the LDL receptor, the IC50 ratio
      being lower than unity (0.73 +/- 0.31, P < 0.05, two-tailed t-test). IC50 values
      themselves were marginally lower in E4/4 than E3/3 subjects (3.7 +/- 1.3 vs. 6.1
      +/- 3.7, P < 0.08). However, there was no difference between E4/4 and E3/3 VLDL
      in competing for the LDL receptor on fibroblasts or between E4/4 and E3/3 LDL in
      competing for the LDL receptor on either cell type. These results suggest that
      inheritance of apoE4 is associated with an increased affinity of VLDL particles
      for LDL receptors on hepatocytes and may partly explain the influence of the E4
      isoform on lipid metabolism.

PMID- 10070024
TI  - Kinetic impairment of nitrogen and muscle glutamine metabolisms in old
      glucocorticoid-treated rats.
AB  - Aged rats are more sensitive to injury, possibly through an impairment of
      nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied
      the metabolic kinetic response of adult and old rats during glucocorticoid
      treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old
      rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by
      intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7
      days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3,
      G5, or G7 groups and were injected with an isovolumic solution of NaCl. One
      control group comprised healthy rats fed ad libitum. The response to aggression
      induced specifically by Dex (i.e., allowing for variations in pair-fed controls)
      appeared later in the aged rats (decrease in nitrogen balance from day 1 in
      adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex
      treatment, whereas the catabolic state worsened until the end of treatment in the
      old rats. Gln homeostasis was not maintained in the aged rats; despite an early
      increase in muscular Gln synthetase activity, the Gln pool was depleted. These
      results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms
      in response to Dex with aging.

PMID- 10070025
TI  - GH insensitivity induced by endotoxin injection is associated with decreased
      liver GH receptors.
AB  - Sepsis induces a state of growth hormone (GH) resistance associated with a
      decrease of circulating insulin-like growth factor (IGF) I, a GH-dependent
      anabolic hormone mainly produced by the liver. To address the mechanisms that
      might trigger GH insensitivity in sepsis, we investigated the regulation of liver
      GH receptor (GHR) and its gene expression by endotoxin. Endotoxin injection in
      rats decreased serum IGF-I and liver GH-binding sites after 10 h. In contrast to
      liver GHR, circulating GH-binding protein (GHBP) levels were not significantly
      reduced after endotoxin injection. The parallel decrease in IGF-I and GHR and in
      their corresponding liver mRNAs suggests that decreased serum IGF-I and liver GHR
      were likely to result from decreased liver synthesis. Although GH administration
      in control animals significantly enhanced serum IGF-I, it did fail to prevent the
      decline in serum IGF-I and liver GH-binding sites in endotoxemic rats. In this
      study, we showed that endotoxin injection induces a state of GH insensitivity
      associated with decreased liver GHR. This decline in GHR, which cannot be
      prevented by exogenous GH, might contribute to the GH insensitivity observed in
      sepsis.

PMID- 10070026
TI  - A surrogate measure of whole body leucine transport across the cell membrane.
AB  - Based on a mass-balance model, a surrogate measure of the whole body leucine
      transport into and out of cells under steady-state conditions was calculated as
      u/DeltaTTR, where u is the infusion rate of (stable label) leucine tracer and
      DeltaTTR is the difference between the tracer-to-tracee ratio of extracellular
      and intracellular leucine. The approach was evaluated in ten healthy subjects [8
      males and 2 females; age, 31 +/- 9 (SD) yr; body mass index, 24.0 +/- 1.6 kg/m2]
      who received a primed (7.58 micromol/kg) constant intravenous infusion (7.58
      micromol. kg-1. h-1) of L-[1-13C]leucine over 180 min (7 subjects) or 240 min (3
      subjects). Five subjects were studied on two occasions >/=1 wk apart to assess
      reproducibility. Blood samples taken during the last 30 min of the leucine
      infusion were used to determine plasma leucine concentration (129 +/- 35
      micromol/l), TTR of leucine (9.0 +/- 1.5%), and TTR of alpha-ketoisocaproic acid
      (6.7 +/- 0.8%). The latter TTR was taken as the measure of the free intracellular
      leucine TTR. The whole body inward and outward transport was 6.66 +/- 3.82
      micromol. kg-1. min-1; the rate of leucine appearance due to proteolysis was 1.93
      +/- 0.24 micromol. kg-1. min-1. A positive linear relationship between the inward
      transport and plasma leucine was observed (P < 0.01), indicating the presence of
      the mass effect of leucine on its own transport. The transport was highly
      variable between subjects (between-subject coefficient of variation 57%) but
      reproducible (within-subject coefficient of variation 17%). We conclude that
      reproducible estimates of whole body transport of leucine across the cell
      membrane can be obtained under steady-state conditions with existing experimental
      and analytical procedures.

PMID- 10070027
TI  - Kinetic profile of overall elimination of 5-methyltetrahydropteroylglutamate in
      rats.
AB  - The in vivo biliary and urinary excretion kinetics of 5
      methyltetrahydropteroylglutamate (5-CH3-H4PteGlu) were studied in rats. During
      infusion at various rates (48-965 nmol. h-1. kg-1), the total body clearance
      (CLtotal) of 5-CH3-H4PteGlu could be attributed almost entirely to the sum of the
      biliary and urinary (CLurine,p) excretion clearances. After a 4-h infusion at the
      highest rate, the 5-CH3-H4PteGlu in the liver was 10 times higher than the
      endogenous level, whereas its polyglutamate form did not increase, suggesting
      that most of the infused 5-CH3-H4PteGlu is not incorporated in the polyglutamate
      pool but is eliminated by excretion. The parallel increase in CLtotal and
      CLurine,p with the increase in infusion rate might result from saturation of
      reabsorption at the renal proximal tubules, since the urinary excretion
      clearance, defined with respect to the kidney concentration, also increased while
      the biliary excretion clearance, defined with respect to the liver concentration,
      remained almost constant. We conclude that the hepatobiliary excretion is a
      relatively low-affinity process with a constant clearance, whereas the renal
      tubular reabsorption is saturated at higher plasma 5-CH3-H4PteGlu concentration (
      approximately 0.5 microM). Urinary excretion becomes the predominant elimination
      route for any excess 5-CH3-H4PteGlu in the body.

PMID- 10070028
TI  - Evaluation of the microdialysis technique in the dog fat pad.
AB  - In the present study the microdialysis technique was evaluated in an isolated
      autoperfused dog fat pad. Concentrations of glucose, lactate, and glycerol were
      measured in interstitial fluid by microdialysis and simultaneously in arterial
      and adipose venous plasma. Adipose tissue blood flow was measured by both 133Xe
      washout and timed weighing of venous blood. Metabolite concentrations in adipose
      venous plasma calculated from interstitial and arterial metabolite concentrations
      and 133Xe washout were positively correlated with measured venous concentrations
      (glucose: r = 0.95, lactate: r = 0.92, glycerol: r = 0.81). Calculated and
      measured venous plasma concentrations did not differ for either glucose or
      lactate, but for glycerol, calculated concentration was on average 76% of
      measured concentration. Metabolite exchanges (Fick's principle) calculated from
      interstitial metabolite concentrations were positively correlated with measured
      exchanges only for lactate (r = 0.69). In conclusion, metabolite concentrations
      in adipose venous plasma can be calculated from microdialysis measurements with
      greater accuracy for glucose and lactate than for glycerol. The precision,
      however, is too low to allow calculation of metabolite exchange when
      arteriovenous metabolite differences are low.

PMID- 10070029
TI  - Effects of arginine vasopressin on cell volume regulation in brain astrocyte in
      culture.
AB  - Astrocytes initially swell when exposed to hypotonic medium but rapidly return to
      normal volume by the process of regulatory volume decrease (RVD). The role that
      arginine vasopressin (AVP) plays in hypotonically mediated RVD in astrocytes is
      unknown. This study was therefore designed to determine whether AVP might play a
      role in astrocyte RVD. With the use of 3-O-[3H]methyl-D-glucose to determine
      water space, AVP treatment resulted in significantly increased 3-O-methyl-D
      glucose water space within 30 s of hypotonic exposure (P = 0.0001) and remained
      significantly elevated above baseline (1. 75 microliter/mg protein) at 5 min (P <
      0.021). In contrast, in untreated cells, complete RVD was achieved by 5 min. At
      30 s, cell volume with AVP treatment was 37% greater than in cells that received
      no treatment (2.9 vs. 2.26 microliter/mg protein, respectively; P < 0.006). The
      rate of cell volume increase (dV/dt) over 30 s was highly significant (0.038 vs.
      0.019 microliter. mg protein-1. s-1 in the AVP-treated vs. untreated group; P =
      0.0004 by regression analysis). Additionally, the rate of cell volume decrease
      over the next 4.5 min was also significantly greater with vasopressin treatment (
      dV/dt = 0.0027 vs. 0.0013 microliter. mg protein-1. s-1; P = 0.0306). The effect
      of AVP was concentration dependent with EC50 = 3.5 nM. To determine whether AVP
      action was receptor mediated, we performed RVD studies in the presence of the V1
      receptor antagonists benzamil and ethylisopropryl amiloride and the V2-receptor
      agonist 1-desamino-8-D-arginine vasopressin (DDAVP). Both V1-receptor antagonists
      significantly inhibited AVP-mediated volume increase by 40-47% (P < 0.005),
      whereas DDAVP had no stimulatory effects above control. Taken together, these
      data suggest that AVP treatment of brain astrocytes in culture appears to
      increase 3-O-methyl-D-glucose water space during RVD through V1 receptor-mediated
      mechanisms. The significance of these findings is presently unclear.

PMID- 10070030
TI  - Genetic disorders of membrane transport. V. The epithelial sodium channel and its
      implication in human diseases.
AB  - The epithelial Na+ channel (ENaC) controls the rate-limiting step in the process
      of transepithelial Na+ reabsorption in the distal nephron, the distal colon, and
      the airways. Hereditary salt-losing syndromes have been ascribed to loss of
      function mutations in the alpha-, beta-, or gamma-ENaC subunit genes, whereas
      gain of function mutations (located in the COOH terminus of the beta- or gamma
      subunit) result in hypertension due to Na+ retention (Liddle's syndrome). In
      mice, gene-targeting experiments have shown that, in addition to the kidney salt
      wasting phenotype, ENaC was essential for lung fluid clearance in newborn mice.
      Disruption of the alpha-subunit resulted in a complete abolition of ENaC-mediated
      Na+ transport, whereas knockout of the beta- or gamma-subunit had only minor
      effects on fluid clearance in lung. Disruption of each of the three subunits
      resulted in a salt-wasting syndrome similar to that observed in humans.

PMID- 10070031
TI  - Nitric oxide. II. Nitric oxide protects in intestinal inflammation.
AB  - This article examines the evidence for nitric oxide (NO) as a protective agent in
      splanchnic ischemia-reperfusion and other forms of acute intestinal inflammation.
      Four major points emerge from this body of data. First, acute intestinal
      inflammation results in an early (i.e., <5 min) and severe decrease in
      endothelium-derived NO. Thus the early trigger event in this condition is a
      functional loss of NO. Second, administration of exogenous NO, NO donors, or NO
      precursors ameliorate splanchnic ischemia-reperfusion and other forms of acute
      intestinal inflammation (i.e., splanchnic trauma). These beneficial effects occur
      at physiological levels of NO when given early in the course of the inflammatory
      state. Third, blockade of nitric oxide synthase (NOS) or gene deletion of NOS
      exacerbates intestinal inflammation. Fourth, there are a variety of signaling
      mechanisms that may mediate the protective effect of NO.

PMID- 10070032
TI  - Experimental enteropathy in athymic and euthymic rats: synergistic role of
      lipopolysaccharide and indomethacin.
AB  - The aim of this study was to investigate the immunologic and microbiological
      bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen
      free (SPF) rats were reared under conventional or SPF conditions. In each group,
      indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was
      evaluated using a previously described ulcer index and tissue myeloperoxidase
      activity. Both euthymic and athymic nude rats developed intestinal ulcers to the
      same degree under conventional conditions but no or minimal ulcer under SPF
      conditions. Pretreatment of conventional rats with intragastric kanamycin
      sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a
      dose-dependent fashion. Interestingly, when lipopolysaccharide was injected
      intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in
      these rats in a dose-dependent manner. We confirmed that kanamycin decreased the
      number of gram-negative bacteria and endotoxin concentration of the small
      intestine in a dose-dependent fashion. These results indicate that indomethacin
      enteropathy is bacteria dependent and does not require a T cell function. Synergy
      between indomethacin and bacterial lipopolysaccharide may play a major role in
      this enteropathy.

PMID- 10070033
TI  - Protein kinase C mediates experimental colitis in the rat.
AB  - Protein kinase C (PKC) plays an important role in the cell signal transduction of
      many physiological processes. In contrast to these physiological responses,
      increases in PKC activity have also been associated with inflammatory disease
      states, including ulcerative colitis. The objective of this study was to examine
      the role of PKC as a causative mediator in initiation of experimentally induced
      colitis in the rat. Colitis was induced in rats by intrarectal (0.6 ml)
      instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS; 75 mg/kg in 50%
      ethanol) or the PKC activator phorbol 12-myristate 13-acetate (PMA; 1.5-3.0 mg/kg
      in 20% ethanol). Gross and histological mucosal damage, mucosal neutrophil
      infiltration, mucosal PKC activity, and PKC protein content for PKC isoforms
      alpha, beta, delta, and epsilon were assessed 2 h to 14 days after an
      inflammatory challenge. Both PKC activity and mucosal injury increased
      significantly within 4 h of TNBS treatment. PKC activity was maximal at 7 days
      and declined at 14 days, whereas mucosal damage became maximal at 1 day and
      declined after 7 days. In contrast, neutrophil infiltration as assessed by
      myeloperoxidase activity only increased 12 h after TNBS treatment, became maximal
      1 day after TNBS administration, and declined thereafter. PKCbeta, -delta, and 
      epsilon were increased in response to TNBS, whereas PKCalpha protein content was
      decreased. The PKC antagonists staurosporine and GF-109203X (25 ng/kg iv) reduced
      TNBS-induced changes in mucosal PKC activity and the degree of mucosal damage. In
      contrast, neutropenia induced by antineutrophil serum treatment did not
      significantly affect the degree of injury or mucosal PKC activity. Furthermore,
      activation of mucosal PKC activity with PMA also induced mucosal damage, which
      was also inhibited by pretreatment with a PKC antagonist. In conclusion, these
      results suggest that increases in PKC activity play a causative role in TNBS
      induced colitis. The PKC-mediated response to TNBS does not appear to involve
      neutrophil infiltration.

PMID- 10070034
TI  - Pronase destroys the lipopolysaccharide receptor CD14 on Kupffer cells.
AB  - CD14 is a lipopolysaccharide (LPS) receptor distributed largely in macrophages,
      monocytes, and neutrophils; however, the role of CD14 in activation of Kupffer
      cells by LPS remains controversial. The purpose of this study was to determine if
      different methods used to isolate Kupffer cells affect CD14. Kupffer cells were
      isolated by collagenase (0.025%) or collagenase-Pronase (0.02%) perfusion and
      differential centrifugation using Percoll gradients and cultured for 24 h before
      experiments. CD14 mRNA was detected by RT-PCR from Kupffer cell total RNA as well
      as from peritoneal macrophages. Western blotting showed that Kupffer cells
      prepared with collagenase possess CD14; however, it was absent in cells obtained
      by collagenase-Pronase perfusion. Intracellular calcium in Kupffer cells prepared
      with collagenase was increased transiently to levels around 300 nM by addition of
      LPS with 5% rat serum, which contains LPS binding protein. This increase in
      intracellular calcium was totally serum dependent. Moreover, LPS-induced
      increases in intracellular calcium in Kupffer cells were blunted significantly
      (40% of controls) when cells were treated with phosphatidylinositol-specific
      phospholipase C, which cleaves CD14 from the plasma membrane. However,
      intracellular calcium did not increase when LPS was added to cells prepared by
      collagenase-Pronase perfusion even in the presence of serum. These cells were
      viable, however, because ATP increased intracellular calcium to the same levels
      as cells prepared with collagenase perfusion. Tumor necrosis factor-alpha (TNF
      alpha) mRNA was increased in Kupffer cells prepared with collagenase perfusion 1
      h after addition of LPS, an effect potentiated over twofold by serum; however,
      serum did not increase TNF-alpha mRNA in cells isolated via collagenase-Pronase
      perfusion. Moreover, treatment with Pronase rapidly decreased CD14 on mouse
      macrophages (RAW 264.7 cells) and Kupffer cells. These findings indicate that
      Pronase cleaves CD14 from Kupffer cells, whereas collagenase perfusion does not,
      providing an explanation for why Kupffer cells do not exhibit a CD14-mediated
      pathway when prepared with procedures using Pronase. It is concluded that Kupffer
      cells indeed contain a functional CD14 LPS receptor when prepared gently.

PMID- 10070035
TI  - Fas activates the JNK pathway in human colonic epithelial cells: lack of a direct
      role in apoptosis.
AB  - Fas is expressed constitutively by colonic epithelial cells, and its ligand is
      expressed by intraepithelial and lamina propria lymphocytes. Fas ligation induces
      apoptosis in colonic epithelial cells and is implicated in the epithelial damage
      seen in ulcerative colitis. To understand the pleiotropic effects of Fas in the
      intestinal mucosa, we have examined signaling pathways activated by Fas in HT-29
      colonic epithelial cells. HT-29 cells were stimulated with anti-Fas in the
      presence or absence of interferon-gamma (IFN-gamma). Activation of mitogen
      activated protein kinase pathways was assessed by kinase assay, Western blots,
      and promoter-reporter assays. Electromobility shift assays were used to assess
      activator protein-1 (AP-1) binding activity. IFN-gamma increases expression of
      Fas on HT-29 cells. Signaling via Fas receptor, as determined by induction of c
      Jun NH2-terminal kinase (JNK) activity and transcriptional activation of AP-1, is
      enhanced in IFN-gamma-primed cells. Dominant-interfering mutants of the JNK
      pathway do not block Fas-mediated apoptosis. Signaling through Fas results in
      activation of JNK and AP-1 binding activity that is increased in the presence of
      IFN-gamma. Inhibition of JNK does not block Fas-mediated apoptosis in these
      cells. Fas-Fas ligand interactions in the intestinal mucosa may lead to complex
      signal transduction cascades and gene regulation that culminate in apoptosis,
      cytokine secretion, or other novel functions.

PMID- 10070036
TI  - Epidermal growth factor regulates fatty acid uptake and metabolism in Caco-2
      cells.
AB  - Epidermal growth factor (EGF) has been reported to stimulate carbohydrate, amino
      acid, and electrolyte transport in the small intestine, but its effects on lipid
      transport are poorly documented. This study aimed to investigate EGF effects on
      fatty acid uptake and esterification in a human enterocyte cell line (Caco-2).
      EGF inhibited cell uptake of [14C]palmitate and markedly reduced its
      incorporation into triglycerides. In contrast, the incorporation in phospholipids
      was enhanced. To elucidate the mechanisms involved, key steps of lipid synthesis
      were investigated. The amount of intestinal fatty acid-binding protein (I-FABP),
      which is thought to be important for fatty acid absorption, and the activity of
      diacylglycerol acyltransferase (DGAT), an enzyme at the branch point of
      diacylglycerol utilization, were reduced. EGF effects on DGAT and on palmitate
      esterification occurred at 2-10 ng/ml, whereas effects on I-FABP and palmitate
      uptake occurred only at 10 ng/ml. This suggests that EGF inhibited palmitate
      uptake by reducing the I-FABP level and shifted its utilization from
      triglycerides to phospholipids by inhibiting DGAT. This increase in phospholipid
      synthesis might play a role in the restoration of enterocyte absorption function
      after intestinal mucosa injury.

PMID- 10070037
TI  - Evidence of T cell receptor beta-chain patterns in inflammatory and
      noninflammatory bowel disease states.
AB  - T cell activation, as defined by expression of relevant cell surface molecules,
      such as the interleukin-2 receptor (CD25), is increased in many chronic relapsing
      diseases, including inflammatory bowel disease (IBD). These T cells are generally
      activated through contact of their clonotypic T cell receptor (TCR) with a
      peptide antigen presented by a major histocompatibility complex molecule. One of
      the putative antigenic contact sites for the TCR is the third complementarity
      determining region (CDR3) of the TCR beta-chain variable region (TCRBV).
      Therefore, analysis of the TCRBV CDR3 provides insight into the diversity of
      antigens encountered by a given T cell population. This study evaluated the TCRBV
      CDR3 usage of the activated intestinal lymphocytes from human subjects with IBD,
      diverticulitis (inflammatory control), and a normal tissue control. Public
      patterns, as demonstrated by shared TCRBV CDR3 amino acid sequences of activated
      intestinal T cell subpopulations, were observed. In particular, a public pattern
      of TCRBV22, a conserved valine in the fifth position, and use of TCRBJ2S1 or
      TCRBJ2S5 was present in three of four Crohn's disease subjects while not present
      in the ulcerative colitis subjects. However, the private patterns of TCRBV CDR3
      region amino acid sequences were far more striking and easily demonstrated in all
      individuals studied, including a normal noninflammatory control. Thus we conclude
      that selective antigenic pressures are prevalent among an individual's activated
      intestinal lymphocytes.

PMID- 10070038
TI  - Effect of central corticotropin-releasing factor on carbon tetrachloride-induced
      acute liver injury in rats.
AB  - Central neuropeptides play important roles in many instances of physiological and
      pathophysiological regulation mediated through the autonomic nervous system. In
      regard to the hepatobiliary system, several neuropeptides act in the brain to
      regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors
      and sympathetic nerve activation are reported to exacerbate experimental liver
      injury. Some stressors are known to stimulate corticotropin-releasing factor
      (CRF) synthesis in the central nervous system and induce activation of
      sympathetic nerves in animal models. The effect of intracisternal CRF on carbon
      tetrachloride (CCl4)-induced acute liver injury was examined in rats.
      Intracisternal injection of CRF dose dependently enhanced elevation of the serum
      alanine aminotransferase (ALT) level induced by CCl4. Elevations of serum
      aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by
      CCl4 were also enhanced by intracisternal CRF injection. Intracisternal injection
      of CRF also aggravated CCl4-induced hepatic histological changes. Intracisternal
      CRF injection alone did not modify the serum ALT level. Intravenous
      administration of CRF did not influence CCl4-induced acute liver injury. The
      aggravating effect of central CRF on CCl4-induced acute liver injury was
      abolished by denervation of hepatic plexus with phenol and by denervation of
      noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch
      vagotomy or atropine treatment. These results suggest that CRF acts in the brain
      to exacerbate acute liver injury through the sympathetic-noradrenergic pathways.

PMID- 10070039
TI  - Transplanted hepatocytes proliferate differently after CCl4 treatment and
      hepatocyte growth factor infusion.
AB  - To understand regulation of transplanted hepatocyte proliferation in the normal
      liver, we used genetically marked rat or mouse cells. Hosts were subjected to
      liver injury by carbon tetrachloride (CCl4), to liver regeneration by a two
      thirds partial hepatectomy, and to hepatocellular DNA synthesis by infusion of
      hepatocyte growth factor for comparative analysis. Transplanted hepatocytes were
      documented to integrate in periportal areas of the liver. In response to CCl4
      treatments after cell transplantation, the transplanted hepatocyte mass increased
      incrementally, with the kinetics and magnitude of DNA synthesis being similar to
      those of host hepatocytes. In contrast, when cells were transplanted 24 h after
      CCl4 administration, transplanted hepatocytes appeared to be injured and most
      cells were rapidly cleared. When hepatocyte growth factor was infused into the
      portal circulation either subsequent to or before cell transplantation and
      engraftment, transplanted cell mass did not increase, although DNA synthesis
      rates increased in cultured primary hepatocytes as well as in intact mouse and
      rat livers. These data suggested that procedures causing selective ablation of
      host hepatocytes will be most effective in inducing transplanted cell
      proliferation in the normal liver. The number of transplanted hepatocytes was not
      increased in the liver by hepatocyte growth factor administration. Repopulation
      of the liver with genetically marked hepatocytes can provide effective reporters
      for studying liver growth control in the intact animal.

PMID- 10070040
TI  - Hepatocyte-specific localization and copper-dependent trafficking of the Wilson's
      disease protein in the liver.
AB  - Wilson's disease is an inherited disorder of copper metabolism characterized by
      hepatic cirrhosis and neuronal degeneration. In this current study, a polyclonal
      antiserum specific for the Wilson's disease ATPase was used to examine the
      hepatic expression of this protein. Immunoblot analysis of lysates from human and
      rat liver detected a single 165-kDa protein, which by immunofluorescence was
      present only in hepatocytes and localized predominantly to the trans-Golgi
      network and exclusively in this compartment under low hepatic copper
      concentrations. Although hepatic copper concentration had no effect on the steady
      state levels of the Wilson's disease protein, copper administration in vivo
      resulted in redistribution of this protein to a cytoplasmic vesicular compartment
      localized toward the hepatocyte canalicular membrane. The relative abundance of
      the Wilson's disease protein in the liver was found to be greatest in the fetus
      before the onset of biliary copper excretion. Taken together, these studies
      reveal a novel posttranslational mechanism of copper homeostasis in vivo
      consistent with the proposed function of the Wilson's disease protein in
      holoceruloplasmin biosynthesis and biliary copper excretion and of relevance to
      the broad clinical heterogeneity observed in this disease.

PMID- 10070041
TI  - beta2-adrenergic receptor-selective agonist clenbuterol prevents Fas-induced
      liver apoptosis and death in mice.
AB  - Stimulation of the cAMP-signaling pathway modulates apoptosis in several cell
      types and inhibits Jo2-mediated apoptosis in cultured rat hepatocytes. No
      information is yet available as to whether the hepatic beta2-adrenergic receptor
      (AR) expression level, including beta2-AR-dependent adenylyl cyclase activation,
      modulates hepatocyte sensitivity to apoptosis in vivo or whether this sensitivity
      can be modified by beta2-AR ligands. We have examined this using C57BL/6 mice, in
      which hepatic beta2-AR densities are low, and transgenic F28 mice, which
      overexpress beta2-ARs and have elevated basal liver adenylyl cyclase activity.
      The F28 mice were resistant to Jo2-induced liver apoptosis and death. The beta-AR
      antagonist propranolol sensitized the F28 livers to Jo2. In normal mice
      clenbuterol, a beta2-AR-specific agonist, considerably reduced Jo2-induced liver
      apoptosis and death; salbutamol, another beta2-AR-selective agonist, also reduced
      Jo2-induced apoptosis and retarded death but with less efficacy than clenbuterol;
      and propranolol blocked the protective effect of clenbuterol. This indicates that
      the expression level of functional beta2-ARs modulates Fas-regulated liver
      apoptosis and that this apoptosis can be inhibited in vivo by giving beta2-AR
      agonists. This may well form the basis for a new therapeutic approach to diseases
      involving abnormal apoptosis.

PMID- 10070042
TI  - Aberrant expression of gastrin-releasing peptide and its receptor by well
      differentiated colon cancers in humans.
AB  - Epithelial cells lining the adult human colon do not normally express gastrin
      releasing peptide (GRP) or its receptor (GRPR). In contrast, approximately one
      third of human colon cancers and cancer cell lines have been shown to express GRP
      binding sites. Because GRPR activation causes the proliferation of many cancer
      cell lines, GRP has been presumed to act as a clinically significant growth
      factor. Yet GRP has not been shown to be expressed by colon cancers in humans nor
      has the effect of GRP and/or GRPR coexpression on tumor behavior been
      investigated. We therefore determined GRP and GRPR expression by
      immunohistochemistry in 50 randomly selected colon cancers resected between 1980
      and 1997, all 37 associated lymph node and liver metastases, and 20 polyps. Tumor
      sections studied were those that contained the margin and adjacent nonmalignant
      epithelium. Overall, 84% of cancers aberrantly expressed GRP or GRPR, with 62%
      expressing both ligand and receptor, whereas expression was not observed in
      adjacent normal epithelium. Consistent with the previously established mitogenic
      capabilities of GRP, tissues coexpressing GRP and GRPR were more likely to
      express proliferating cell nuclear antigen than tissues not expressing both
      ligand and receptor. Yet GRP/GRPR coexpression was seen with equal frequency in
      stage A as in stage D cancers and was only detected in 1 in 37 metastases.
      Furthermore, Kaplan-Meier analysis did not reveal any difference in patient
      survival between those whose tumors did or did not express GRP/GRPR. In contrast,
      GRP/GRPR coexpression was found in all well-differentiated tumor regions, whereas
      poorly differentiated tissues never coexpressed GRP/GRPR. Overall, these data
      indicate that, although GRP is a mitogen, it is not a clinically significant
      growth factor in human colon cancers. Rather, the strong association of GRP/GRPR
      coexpression with tumor differentiation raises the possibility that these
      proteins primarily act in vivo as morphogens.

PMID- 10070044
TI  - Bcl-2 inhibits ischemia-reperfusion-induced apoptosis in the intestinal
      epithelium of transgenic mice.
AB  - Little is known about the effects of ischemia-reperfusion on the inductive,
      commitment, or execution phases of apoptosis. We have created a genetically
      defined model to study the response of small intestinal epithelial cells to
      ischemia-reperfusion injury as a function of their proliferative status and
      differentiation. Occlusion of the superior mesenteric artery for 20 min in adult
      FVB/N or C57BL/6 mice results in the appearance of TUNEL-positive apoptotic cells
      in the jejunal epithelium within 4 h, with a maximum response occurring at 24 h.
      Stimulation of apoptosis is greater in postmitotic, differentiated epithelial
      cells located in the upper portions of villi compared with undifferentiated,
      proliferating cells in the crypts of Lieberkuhn (7-fold vs. 2-fold relative to
      sham-operated controls). Comparisons of p53(+/+) and p53(-/-) mice established
      that the apoptosis is p53 independent. To further characterize this response, we
      generated FVB/N transgenic mice that express human Bcl-2 in epithelial cells
      distributed from the base of crypts to the tips of their associated villi. The
      fivefold elevation in steady-state Bcl-2 concentration is not accompanied by
      detectable changes in the levels or cellular distributions of the related anti
      apoptotic regulator Bcl-xL or of the proapoptotic regulators Bax and Bak and does
      not produce detectable effects on basal proliferation, differentiation, or death
      programs. The apoptotic response to ischemia-reperfusion is reduced twofold in
      the crypts and villi of transgenic mice compared with their normal littermates.
      These results suggest that both undifferentiated and differentiated cells undergo
      a commitment phase that is sensitive to Bcl-2. Forced expression of Bcl-2 also
      suppressed the p53-dependent death that occurs in proliferating crypt epithelial
      cells following gamma-irradiation. Thus suppressibility by Bcl-2 operationally
      defines a common feature of the apoptosis induced in the crypt epithelium by
      these two stimuli.

PMID- 10070043
TI  - Goblet cell-specific expression mediated by the MUC2 mucin gene promoter in the
      intestine of transgenic mice.
AB  - The regulation of MUC2, a major goblet cell mucin gene, was examined by
      constructing transgenic mice containing bases -2864 to +17 of the human MUC2 5'
      flanking region fused into the 5'-untranslated region of a human growth hormone
      (hGH) reporter gene. Four of eight transgenic lines expressed reporter. hGH
      message expression was highest in the distal small intestine, with only one line
      expressing comparable levels in the colon. This contrasts with endogenous MUC2
      expression, which is expressed at its highest levels in the colon.
      Immunohistochemical analysis indicated that goblet cell-specific expression of
      reporter begins deep in the crypts, as does endogenous MUC2 gene expression.
      These results indicate that the MUC2 5'-flanking sequence contains elements
      sufficient for the appropriate expression of MUC2 in small intestinal goblet
      cells. Conversely, elements located outside this region appear necessary for
      efficient colonic expression, implying that the two tissues utilize different
      regulatory elements. Thus many, but not all, of the elements necessary for MUC2
      gene regulation reside between bases -2864 and +17 of the 5'-flanking region.

PMID- 10070045
TI  - Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in
      portal hypertensive rats.
AB  - Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the
      hyperdynamic circulatory state of portal hypertension. Recent evidence also
      indicates that increased tumor necrosis factor-alpha (TNF-alpha) production is
      involved in the pathogenesis of this hemodynamic abnormality. This study was
      aimed at investigating in rats with portal vein stenosis (PVS) the effects on
      splanchnic hemodynamics of blocking circulating TNF-alpha and the factors
      mediating the vascular action of this cytokine in this setting. Anti-TNF-alpha
      polyclonal antibodies or placebo was injected into rats (n = 96) before and 4
      days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS
      (long-term inhibition). Short-term TNF-alpha inhibition reduced portal venous
      inflow and cardiac index and increased splanchnic and systemic resistance. Portal
      pressure was unchanged, but portal-systemic shunting was decreased. After long
      term TNF-alpha inhibition, portal venous inflow and portal pressure were
      unchanged, but arterial pressure and systemic resistance rose significantly. Anti
      TNF-alpha PVS rats exhibited lower increments of systemic resistance after Nomega
      nitro-L-arginine methyl ester and indomethacin administration and lower serum
      levels of TNF-alpha, nitrates-nitrites, and 6-keto-PGF1alpha, both over the short
      and the long term. Serum glucagon levels rose after long-term inhibition. In
      conclusion, the specific role played by TNF-alpha in the development of the
      hyperdynamic state of portal hypertension appears to be mainly mediated through
      an increased release of nitric oxide and prostacyclin. Maintenance of the
      splanchnic hyperemia after long-term TNF-alpha inhibition could be due to a
      compensatory release of glucagon.

PMID- 10070046
TI  - Diazepam-binding inhibitor33-50 elicits Ca2+ oscillation and CCK secretion in STC
      1 cells via L-type Ca2+ channels.
AB  - We recently isolated and characterized 86-amino acid CCK-releasing peptide from
      porcine intestinal mucosa. The sequence of this peptide is identical to that of
      porcine diazepam-binding inhibitor (DBI). Intraduodenal administration of DBI
      stimulates the CCK release and elicits pancreatic secretion in rats. In this
      study we utilized a murine tumor cell line (STC-1 cells) that contains CCK to
      examine if DBI directly acts on these cells to stimulate CCK release. We
      investigated the cellular mechanisms responsible for this action. We showed that
      DBI33-50, a biologically active fragment of DBI1-86, significantly stimulated CCK
      secretion in STC-1 cells. This action was abolished by Ca2+-free medium. The mean
      basal intracellular Ca2+ concentration ([Ca2+]i) was 52 nM in fura 2-loaded STC-1
      cells. DBI33-50 (1-1,000 nM) elicited Ca2+ oscillations; DBI33-50 (10 nM)
      increased the oscillation frequency to 5 cycles/10 min and elicited a net [Ca2+]i
      increase (peak - basal) to 157 nM. In contrast, bombesin and forskolin caused an
      initial transient [Ca2+]i followed by a small sustained [Ca2+]i plateau.
      Withdrawal of extracellular Ca2+ abolished Ca2+ oscillations stimulated by DBI33
      50. L-type Ca2+ channel blockers nifedipine and diltiazem (3-10 microM) markedly
      attenuated DBI-stimulated Ca2+ oscillations. In other cell types L-type Ca2+
      channels are activated by cAMP-protein kinase A. DBI33-50 failed to stimulate
      cAMP formation in STC-1 cells. Similarly, DBI33-50 had no effect on myo-inositol
      1,4, 5-trisphosphate concentration ([IP3]), whereas bombesin caused an eightfold
      increase in [IP3] over basal. In addition, inhibitors of phospholipase C (U
      73122), phospholipase A2 (ONO-RS-082), and protein tyrosine kinase (genistein)
      did not alter the Ca2+ oscillations elicited by DBI33-50. It appears that DBI33
      50 acts directly on STC-1 cells to elicit Ca2+ oscillations via the voltage
      dependent L-type Ca2+ channels, resulting in the secretion of CCK. Mediation of
      this action is by intracellular mechanisms independent of the traditional signal
      transduction pathways, including phospholipase C, phospholipase A2, protein
      tyrosine kinase, and cAMP systems.

PMID- 10070047
TI  - Prolonged colonic epithelial hyporesponsiveness after colitis: role of inducible
      nitric oxide synthase.
AB  - Colonic epithelial secretion is an important host defense mechanism. We examined
      whether a bout of colitis would produce long-lasting changes in epithelial
      function that persisted after resolution of mucosal inflammation. Colitis was
      induced in rats with intracolonic trinitrobenzenesulfonic acid. Six weeks later,
      colonic damage and inducible nitric oxide synthase (iNOS) mRNA expression and
      activity were measured. Segments of distal colon were mounted in Ussing chambers
      for measurement of permeability and responsiveness to secretory stimuli. Basal
      electrolyte transport parameters and permeability were not different from
      untreated controls. Despite normal macroscopic and histological appearance,
      secretory responses to electrical field stimulation (EFS), isobutylmethylxanthine
      (IBMX), and carbachol were significantly depressed (by 60-70%) relative to
      controls. iNOS mRNA expression and enzyme activity were significantly elevated.
      Dexamethasone reversed epithelial hyporesponsiveness and significantly reduced
      iNOS mRNA expression. A selective iNOS inhibitor normalized the secretory
      responses to EFS and IBMX but not to carbachol. These data suggest that ongoing
      synthesis of nitric oxide by iNOS contributes to chronic suppression of
      epithelial secretory function after episodes of colitis.

PMID- 10070048
TI  - Effects of duodenal distension on antropyloroduodenal pressures and perception
      are modified by hyperglycemia.
AB  - Marked hyperglycemia (blood glucose approximately 15 mmol/l) affects
      gastrointestinal motor function and modulates the perception of gastrointestinal
      sensations. The aims of this study were to evaluate the effects of mild
      hyperglycemia on the perception of, and motor responses to, duodenal distension.
      Paired studies were done in nine healthy volunteers, during euglycemia (
      approximately 4 mmol/l) and mild hyperglycemia ( approximately 10 mmol/l), in
      randomized order, using a crossover design. Antropyloroduodenal pressures were
      recorded with a manometric, sleeve-side hole assembly, and proximal duodenal
      distensions were performed with a flaccid bag. Intrabag volumes were increased at
      4-ml increments from 12 to 48 ml, each distension lasting for 2.5 min and
      separated by 10 min. Perception of the distensions and sensations of fullness,
      nausea, and hunger were evaluated. Perceptions of distension (P < 0.001) and
      fullness (P < 0.05) were greater and hunger less (P < 0.001) during hyperglycemia
      compared with euglycemia. Proximal duodenal distension stimulated pyloric tone (P
      < 0.01), isolated pyloric pressure waves (P < 0.01), and duodenal pressure waves
      (P < 0.01). Compared with euglycemia, hyperglycemia was associated with increases
      in pyloric tone (P < 0.001), the frequency (P < 0.05) and amplitude (P < 0.01) of
      isolated pyloric pressure waves, and the frequency of duodenal pressure waves (P
      < 0.001) in response to duodenal distension. Duodenal compliance was less (P <
      0.05) during hyperglycemia compared with euglycemia, but this did not account for
      the effects of hyperglycemia on perception. We conclude that both the perception
      of, and stimulation of pyloric and duodenal pressures by, duodenal distension are
      increased by mild hyperglycemia. These observations are consistent with the
      concept that the blood glucose concentration plays a role in the regulation of
      gastrointestinal motility and sensation.

PMID- 10070049
TI  - Regulation of IGF binding protein-1 in hep G2 cells by cytokines and reactive
      oxygen species.
AB  - The liver is a major site of synthesis for insulin-like growth factor binding
      protein (IGFBP)-1. Because IGFBP-1 inhibits many anabolic actions of IGF-I,
      increases in IGFBP-1 may be partly responsible for the decrease in lean body mass
      observed in catabolic/inflammatory conditions. This study aimed to determine in
      Hep G2 cells 1) the sensitivity of IGFBP-1 synthesis to treatment with
      interleukin (IL)-1, tumor necrosis factor-alpha (TNF-alpha), and IL-6, 2) the
      ability of reactive oxygen species (ROS) to enhance IGFBP-1 production, and 3)
      the role of ROS in mediating cytokine-induced increases in IGFBP-1. Hep G2 cells
      responded to IL-1beta, TNF-alpha, and IL-6 with maximal 8- to 10-fold increases
      in IGFBP-1 production. Although the maximal responsiveness of cells treated with
      TNF-alpha and IL-6 was 20-30% less than that with IL-1beta, cells demonstrated a
      similar sensitivity to all cytokines (half-maximal responsive dose of
      approximately 10 ng/ml). A low concentration (3 ng/ml) of all three cytokines had
      an additive effect on IGFBP-1 production. Cytokines also increased IGFBP-1 mRNA.
      The half-life of IGFBP-1 mRNA was approximately 4 h and not altered by IL-1beta.
      Incubation with ROS, including H2O2 and nitric oxide (NO) donors, resulted in a
      relatively smaller increase in IGFBP-1. However, preincubating Hep G2 cells with
      various free radical scavengers and NO synthase and eicosanoid inhibitors failed
      to prevent or attenuate cytokine-induced increases in IGFBP-1. Finally,
      preincubating cells with pyrrolidinedithiocarbamate (PDTC) but not SN50
      (inhibitors of nuclear factor-kappaB activation and nuclear translocation,
      respectively) attenuated increases in IGFBP-1 induced by IL-1. These results
      indicate that 1) proinflammatory cytokines directly enhance IGFBP-1 synthesis by
      stimulating transcription without altering mRNA stability, 2) addition of
      exogenous ROS also stimulates IGFBP-1 production but to a smaller extent than
      cytokines, and 3) the cytokine-induced increase in IGFBP-1 production is not
      mediated by endogenous production of ROS or eicosanoids but appears to at least
      partially involve a PDTC-sensitive pathway.

PMID- 10070050
TI  - Hepatocyte nuclear factor-4 regulates intestinal expression of the guanylin/heat
      stable toxin receptor.
AB  - We have investigated the regulation of gene transcription in the intestine using
      the guanylyl cyclase C (GCC) gene as a model. GCC is expressed in crypts and
      villi in the small intestine and in crypts and surface epithelium of the colon.
      DNase I footprint, electrophoretic mobility shift assay (EMSA), transient
      transfection assays, and mutagenesis experiments demonstrated that GCC
      transcription is regulated by a critical hepatocyte nuclear factor-4 (HNF-4)
      binding site between bp -46 and -29 and that bp -38 to -36 were essential for
      binding. Binding of HNF-4 to the GCC promoter was confirmed by competition EMSA
      and by supershift EMSA. In Caco-2 and T84 cells, which express both GCC and HNF
      4, the activity of GCC promoter and/or luciferase reporter plasmids containing
      128 or 1973 bp of 5'-flanking sequence was dependent on the HNF-4 binding site in
      the proximal promoter. In COLO-DM cells, which express neither GCC nor HNF-4,
      cotransfection of GCC promoter/luciferase reporter plasmids with an HNF-4
      expression vector resulted in 23-fold stimulation of the GCC promoter. Mutation
      of the HNF-4 binding site abolished this transactivation. Transfection of COLO-DM
      cells with the HNF-4 expression vector stimulated transcription of the endogenous
      GCC gene as well. These results indicate that HNF-4 is a key regulator of GCC
      expression in the intestine.

PMID- 10070051
TI  - Evidence for an anion exchange mechanism for uptake of conjugated bile acid from
      the rat jejunum.
AB  - Absorption of conjugated bile acids from the small intestine is very efficient.
      The mechanisms of jejunal absorption are not very well understood. The aim of
      this study was to clarify the mechanism of absorption of conjugated bile acid at
      the apical membrane of jejunal epithelial cells. Brush-border membrane vesicles
      from intestinal epithelial cells of the rat were prepared. Absorption of two
      taurine-conjugated bile acids that are representative of endogenous bile acids in
      many variate vertebrate species were studied. In ileal, but not jejunal brush
      border membrane vesicles, transport of conjugated bile acids was cis-stimulated
      by sodium. Transport of conjugated bile acids was trans-stimulated by bicarbonate
      in the jejunum. Absorption of conjugated dihydroxy-bile acids was almost twice as
      fast as of trihydroxy-bile acids. Coincubation with other conjugated bile acids,
      bromosulfophthalein, and DIDS, as well as by incubation in the cold inhibited the
      transport rate effectively. Absorption of conjugated bile acids in the jejunum
      from the rat is driven by anion exchange and is most likely an antiport
      transport.

PMID- 10070052
TI  - Rat liver endothelial cell glutamine transporter and glutaminase expression
      contrast with parenchymal cells.
AB  - Despite the central role of the liver in glutamine homeostasis in health and
      disease, little is known about the mechanism by which this amino acid is
      transported into sinusoidal endothelial cells, the second most abundant hepatic
      cell type. To address this issue, the transport of L-glutamine was functionally
      characterized in hepatic endothelial cells isolated from male rats. On the basis
      of functional analyses, including kinetics, cation substitution, and amino acid
      inhibition, it was determined that a Na+-dependent carrier distinct from system N
      in parenchymal cells, with properties of system ASC or B0, mediated the majority
      of glutamine transport in hepatic endothelial cells. These results were supported
      by Northern blot analyses that showed expression of the ATB0 transporter gene in
      endothelial but not parenchymal cells. Concurrently, it was determined that,
      whereas both cell types express glutamine synthetase, hepatic endothelial cells
      express the kidney-type glutaminase isozyme in contrast to the liver-type isozyme
      in parenchymal cells. This represents the first report of ATB0 and kidney-type
      glutaminase isozyme expression in the liver, observations that have implications
      for roles of specific cell types in hepatic glutamine homeostasis in health and
      disease.

PMID- 10070053
TI  - Cholic acid aids absorption, biliary secretion, and phase transitions of
      cholesterol in murine cholelithogenesis.
AB  - Cholic acid is a critical component of the lithogenic diet in mice. To determine
      its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic
      acid to C57L/J male mice, which because of lith genes have 100% gallstone
      prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid
      secretion rates, hepatic cholesterol and bile salt synthesis, and intestinal
      cholesterol absorption. After hepatic conjugation with taurine, cholate replaced
      most tauro-beta-muricholate in bile. Dietary cholic acid plus cholesterol
      increased bile flow and biliary lipid secretion rates and reduced cholesterol
      7alpha-hydroxylase activity significantly mostly via deoxycholic acid, cholate's
      bacterial 7alpha-dehydroxylation product but did not downregulate cholesterol
      biosynthesis. Intestinal cholesterol absorption doubled, and biliary cholesterol
      crystallized as phase boundaries shifted. Feeding mice 1% cholesterol alone
      produced no lithogenic or homeostatic effects. We conclude that in mice cholic
      acid promotes biliary cholesterol hypersecretion and cholelithogenesis by
      enhancing intestinal absorption, hepatic bioavailability, and phase separation of
      cholesterol in bile.

PMID- 10070054
TI  - Physiological changes in blood glucose do not affect gastric compliance and
      perception in normal subjects.
AB  - Marked hyperglycemia (blood glucose approximately 14 mmol/l) slows gastric
      emptying and affects the perception of sensations arising from the gut. Elevation
      of blood glucose within the physiological range also slows gastric emptying. This
      study aimed to determine whether physiological changes in blood glucose affect
      proximal gastric compliance and/or the perception of gastric distension in the
      fasting state. Paired studies were conducted in 10 fasting healthy volunteers. On
      a single day, isovolumetric and isobaric distensions of the proximal stomach were
      performed using an electronic barostat while the blood glucose concentration was
      maintained at 4 and 9 mmol/l in random order. Sensations were quantified using
      visual analog scales. The blood glucose concentration had no effect on the
      pressure-volume relationship during either isovolumetric or isobaric distensions
      or the perception of gastric distension. At both blood glucose concentrations,
      the perceptions of fullness, nausea, bloating, and abdominal discomfort, but not
      hunger or desire to eat, were related to intrabag volume (P </= 0.002) and
      pressure (P </= 0.01). We conclude that, in the fasted state, elevations of blood
      glucose within the physiological range do not affect proximal gastric compliance
      or the perception of gastric distension.

PMID- 10070055
TI  - Regional effects of cholecystokinin octapeptide on colonic phasic and tonic
      motility in healthy humans.
AB  - The aim of this study was to assess in nine healthy subjects the effects of CCK
      octapeptide (CCK-8) on colonic tonic activity, measured by a barostat, and phasic
      activity, measured by manometry. On 2 consecutive days, recordings were performed
      in the unprepared proximal and distal colons during intravenous infusion of
      saline and CCK-8 at 5, 20, and 40 ng. kg-1. h-1. In the proximal colon CCK-8
      induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic relaxation with an
      increase in barostat bag volume to 156 +/- 25 and 157 +/- 19% of basal (P < 0.01)
      and a decrease in phasic activity to 72 +/- 7 and 76 +/- 7% of basal (P < 0.01).
      In the distal colon, CCK-8 induced, at the 20 and 40 ng. kg-1. h-1 doses, a tonic
      relaxation (increase in intrabag volume to 133 +/- 12 and 149 +/- 15%,
      respectively; P < 0.01), whereas phasic activity increased (128 +/- 8 and 132 +/-
      6%, respectively; P < 0.01). Effects of CCK-8 on tonic and phasic activities are
      different according to the colonic segment. Because meals induce colonic tonic
      contraction, our results suggest that CCK, as a hormone, is not an important
      mediator of the response of the colon to feeding in humans.

PMID- 10070056
TI  - Interaction of asparagine and EGF in the regulation of ornithine decarboxylase in
      IEC-6 cells.
AB  - Our laboratory has shown that asparagine (ASN) stimulates both ornithine
      decarboxylase (ODC) activity and gene expression in an intestinal epithelial cell
      line (IEC-6). The effect of ASN is specific, and other A- and N-system amino
      acids are almost as effective as ASN when added alone. In the present study,
      epidermal growth factor (EGF) was unable to increase ODC activity in cells
      maintained in a salt-glucose solution (Earle's balanced salt solution). However,
      the addition of ASN (10 mM) in the presence of EGF (30 ng/ml) increased the
      activity of ODC 0.5- to 4-fold over that stimulated by ASN alone. EGF also showed
      induction of ODC with glutamine and alpha-aminoisobutyric acid, but ODC induction
      was maximum with ASN and EGF. Thus the mechanism of the interaction between ASN
      and EGF is important for understanding the regulation of ODC under physiological
      conditions. Therefore, we examined the expression of the ODC gene and those for
      several protooncogenes under the same conditions. Increased expression of the
      genes for c-Jun and c-Fos but not for ODC occurred with EGF alone. The addition
      of ASN did not further increase the expression of the protooncogenes, but the
      combination of EGF and ASN further increased the expression of ODC over that of
      ASN alone. Western analysis showed no significant difference in the level of ODC
      protein in Earle's balanced salt solution, ASN, EGF, or EGF plus ASN. Addition of
      cycloheximide during ASN and ASN plus EGF treatment completely inhibited ODC
      activity without affecting the level of ODC protein. These results indicated that
      1) the increased expression of protooncogenes in response to EGF is independent
      of increases in ODC activity and 2) potentiation between EGF and ASN on ODC
      activity may not be due to increased gene transcription but to posttranslational
      regulation and the requirement of ongoing protein synthesis involving a specific
      factor dependent on ASN.

PMID- 10070057
TI  - Enteropathogenic E. coli attenuates secretagogue-induced net intestinal ion
      transport but not Cl- secretion.
AB  - Enteric bacterial pathogens often increase intestinal Cl- secretion.
      Enteropathogenic Escherichia coli (EPEC) does not stimulate active ion secretion.
      In fact, EPEC infection decreases net ion transport in response to classic
      secretagogues. This has been presumed to reflect diminished Cl- secretion. The
      aim of this study was to investigate the influence of EPEC infection on specific
      intestinal epithelial ion transport processes. T84 cell monolayers infected with
      EPEC were used for these studies. EPEC infection significantly decreased short
      circuit current (Isc) in response to carbachol and forskolin, yet 125I efflux
      studies revealed no difference in Cl- channel activity. There was also no
      alteration in basolateral K+ channel or Na+-K+-2Cl- cotransport activity.
      Furthermore, net 36Cl- flux was not decreased by EPEC. No alterations in either
      K+ or Na+ transport could be demonstrated. Instead, removal of basolateral
      bicarbonate from uninfected monolayers yielded an Isc response approximating that
      observed with EPEC infection, whereas bicarbonate removal from EPEC-infected
      monolayers further diminished Isc. These studies suggest that the reduction in
      stimulated Isc is not secondary to diminished Cl- secretion. Alternatively,
      bicarbonate-dependent transport processes appear to be perturbed.

PMID- 10070058
TI  - Paracellular glucose transport plays a minor role in the unanesthetized dog.
AB  - Traditionally, intestinal glucose absorption was thought to occur through active,
      carrier-mediated transport. However, proponents of paracellular transport have
      argued that previous experiments neglected effects of solvent drag coming from
      high local concentrations of glucose at the brush-border membrane. The purpose of
      this study was to evaluate glucose absorption in the awake dog under conditions
      that would maximize any contribution of paracellular transport. Jejunal Thiry
      Vella loops were constructed in six female mongrel dogs. After surgical recovery,
      isotonic buffers containing L-glucose as the probe for paracellular permeability
      were given over 2-h periods by constant infusion pump. At physiological
      concentrations of D-glucose (1-50 mM), the fractional absorption of L-glucose was
      only 4-7% of total glucose absorption. Infusion of supraphysiological
      concentrations (150 mM) of D-glucose, D-maltose, or D-mannitol yielded low
      fractional absorptions of L-glucose (2-5%), so too did complex or nonabsorbable
      carbohydrates. In all experiments, there was significant fractional water
      absorption (5-19%), a prerequisite for solvent drag. Therefore, with even up to
      high concentrations of luminal carbohydrates in the presence of significant water
      absorption, the relative contribution of paracellular glucose absorption remained
      low.

PMID- 10070059
TI  - Phospholamban-to-SERCA2 ratio controls the force-frequency relationship.
AB  - The force-frequency relationship (FFR) describes the frequency-dependent
      potentiation of cardiac contractility. The interaction of the sarcoplasmic
      reticulum Ca2+-adenosinetriphosphatase (SERCA2) with its inhibitory protein
      phospholamban (PLB) might be involved in the control of the FFR. The FFR was
      analyzed in two systems in which the PLB-to-SERCA2 ratio was modulated. Adult
      rabbit cardiac myocytes were transduced with adenovirus encoding for SERCA2, PLB,
      and beta-galactosidase (control). After 3 days, the relative PLB/SERCA2 values
      were significantly different between groups (SERCA2, 0.5; control, 1.0; PLB,
      4.5). SERCA2 overexpression shortened relaxation by 23% relative to control,
      whereas PLB prolonged relaxation by 39% and reduced contractility by 47% (0.1
      Hz). When the stimulation frequency was increased to 1.5 Hz, myocyte
      contractility was increased by 30% in control myocytes. PLB-overexpressing
      myocytes showed an augmented positive FFR (+78%), whereas SERCA2-transduced
      myocytes displayed a negative FFR (-15%). A more negative FFR was also found in
      papillary muscles from SERCA2 transgenic mice. These findings demonstrate that
      the ratio of phospholamban to SERCA2 is an important component in the control of
      the FFR.

PMID- 10070060
TI  - Proapoptotic effects of ANG II in human coronary artery endothelial cells: role
      of AT1 receptor and PKC activation.
AB  - Anoxia-reoxygenation, tumor necrosis factor-alpha (TNF-alpha), and angiotensin II
      (ANG II) have been shown to induce apoptosis in myocytes. However, the role of
      these mediators in causing apoptosis of human coronary artery endothelial cells
      (HCAEC) is not known. This study was designed to examine the interaction of these
      mediators in induction of apoptosis in HCAEC. Cultured HCAEC were exposed to
      anoxia-reoxygenation, TNF-alpha, and ANG II. TNF-alpha enhanced apoptosis of
      HCAEC (determined by DNA nick-end labeling in situ and DNA laddering) caused by
      anoxia-reoxygenation. ANG II increased apoptosis beyond that caused by anoxia
      reoxygenation and TNF-alpha. Apoptosis caused by ANG II was reduced by losartan,
      a specific ANG II type 1 receptor (AT1R) blocker, whereas PD-123,177, a specific
      ANG II type 2 receptor blocker, under identical conditions had minimal effect.
      The proapoptotic effects of ANG II were associated with the activation of protein
      kinase C (PKC). The importance of PKC activation as a signal transduction
      mechanism became evident in experiments wherein treatment of HCAEC with a
      specific inhibitor of PKC activation decreased ANG II-mediated apoptosis. Thus
      AT1R activation appears to be responsible for apoptosis caused by ANG II in
      HCAEC, and AT1R activation-mediated apoptosis involves activation of PKC.

PMID- 10070061
TI  - Regional differences in effects of E-4031 within the sinoatrial node.
AB  - Effects of block of the rapid delayed rectifier K+ current (IK,r) by E-4031 on
      the electrical activity of small ball-like tissue preparations from different
      regions of the rabbit sinoatrial node were measured. The effects of partial block
      of IK,r by 0.1 microM E-4031 varied in different regions of the node. In tissue
      from the center of the node spontaneous activity was generally abolished, whereas
      in tissue from the periphery spontaneous activity persisted, although the action
      potential was prolonged, the maximum diastolic potential was decreased, and the
      spontaneous activity slowed. After partial block of IK,r, the electrical activity
      of peripheral tissue was more like that of central tissue under normal
      conditions. One possible explanation of these findings is that the density of
      IK,r is greater in the periphery of the node; this would explain the greater
      resistance of peripheral tissue to IK,r block and help explain why, under normal
      conditions, the maximum diastolic potential is more negative, the action
      potential is shorter, and pacemaking is faster in the periphery.

PMID- 10070062
TI  - TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat
      cardiomyocytes treated with doxorubicin.
AB  - Differential display identified that gene fragment HA220 homologous to the
      transcriptional activator factor II 250 (TAFII250) gene, or CCG1, was increased
      in hypertrophied rodent heart. To determine whether TAFII250 gene expression is
      modified after cardiac damage, we measured TAFII250 expression in vivo in mouse
      hearts after injection of the cardiotoxic agent doxorubicin (DXR) and in vitro in
      DXR-treated isolated rat neonatal cardiomyocytes. In vivo atrial natriuretic
      factor (ANF), beta-myosin heavy chain (beta-MHC), Egr-1, and TAFII250 expression
      increased with dose and time after a single DXR injection, but only ANF and beta
      MHC expression were increased after multiple injections. After DXR treatment of
      neonatal cardiomyocytes we found decreased ANF, alpha-MHC, Egr-1, and TAFII250
      expression. Expression of the TAFII250-regulated genes, the D-type cyclins, was
      increased after a single injection in adult mice and was decreased in DXR-treated
      cardiomyocytes. Thus expression of Erg-1, TAFII250, and the D-type cyclins is
      modulated after cardiotoxic damage in adult and neonatal heart.

PMID- 10070063
TI  - Inhibition of NO synthesis or endothelium removal reveals a vasoconstrictor
      effect of insulin on isolated arterioles.
AB  - In this study we tested the hypothesis that insulin may differentially affect
      isolated arterioles from red (RGM) and white gastrocnemius muscles (WGM) because
      of their differences in function and metabolic profile. We also determined
      whether the responses of these arterioles are endothelium dependent and mediated
      by either prostaglandins or nitric oxide (NO). Arterioles were isolated,
      pressurized to 85 mmHg, equilibrated in Krebs bicarbonate-buffered solution (pH
      7.4) gassed with 10% O2 (5% CO2-85% N2), and studied in a no-flow state. Control
      diameters for first-order arterioles from RGM averaged 77 +/- 8 micrometers and
      from WGM averaged 77 +/- 5 micrometers. Cumulative dose-response curves to
      insulin (10 microU/ml, 100 microU/ml, 1 mU/ml, and 10 mU/ml) were obtained in
      arterioles before and after endothelium removal or administration of either
      indomethacin (Indo, 10(-5) M) or NG-nitro-L-arginine (L-NNA, 10(-4) M). Insulin
      evoked concentration-dependent increases in control diameter of intact RGM and
      WGM arterioles of 6-26% and 9-28%, respectively. Indo was without any effect on
      insulin-induced dilation in RGM and WGM arterioles. Insulin-evoked dilation in
      both RGM and WGM arterioles was completely inhibited and converted to
      vasoconstriction by endothelium removal and administration of L-NNA. These
      results indicate that in endothelium-intact arterioles from RGM and WGM, insulin
      evokes an endothelium-dependent dilation that is equivalent and mediated by NO.
      In contrast, in the absence of a functional endothelium, insulin evokes
      arteriolar constriction. The finding that insulin can constrict arterioles, at
      physiological concentrations, suggests that insulin may play a more significant
      role in the regulation of vascular tone and total peripheral resistance than
      previously appreciated.

PMID- 10070064
TI  - Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated
      vasodilation.
AB  - Normal pregnancy is characterized by reduced systemic vascular resistance, which
      may be mediated by nitric oxide (NO). We compared endothelial vasomotor function
      in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester)
      to 37 healthy age-matched controls. With external ultrasound, brachial artery
      diameter was measured at rest, during reactive hyperemia [with increased flow
      causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin
      (causing endothelium-independent dilation). Compared with controls, resting flow
      and brachial artery diameter were significantly higher during the middle and last
      trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased
      from the first trimester (by 26%), reaching the highest value in the last
      trimester (to 47% above nonpregnant values). FMD was significantly correlated to
      pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin
      induced dilation was similar in pregnant and nonpregnant women. A longitudinal
      study of eight women evaluated in the first, middle, and last trimesters
      confirmed an increase in FMD throughout pregnancy. The study supports the idea
      that basal and stimulated NO activity is enhanced in normal pregnancy and may
      contribute to the decrease in peripheral resistance.

PMID- 10070065
TI  - alpha1-Adrenergic stimulation of FGF-2 promoter in cardiac myocytes and in adult
      transgenic mouse hearts.
AB  - Fibroblast growth factor (FGF-2), a mitogenic, angiogenic, and cardioprotective
      agent, is reported to be released from the postnatal heart by a mechanism of
      transient remodeling of the sarcolemma during contraction. This release can be
      increased with adrenergic stimulation. RNA blotting was used to assess whether
      FGF-2 synthesis in neonatal rat cardiomyocytes might also be regulated by
      adrenergic stimulation. FGF-2 RNA levels were increased after treatment with
      norepinephrine for 6 h or with the alpha-adrenergic agonist phenylephrine for 48
      h. To assess an effect on transcription, neonatal rat cardiomyocytes were
      transfected with a hybrid rat FGF-2 promoter/luciferase gene (-1058FGFp.luc) and
      treated with norepinephrine or phenylephrine for 6 or 48 h, respectively. FGF-2
      promoter activity was increased two- to sevenfold in an alpha1-specific manner.
      Putative phenylephrine-responsive elements (PEREs) were identified at positions 
      780 and -761 relative to a major transcription initiation site. However, deletion
      analysis of -1058FGFp.luc showed that the phenylephrine response was independent
      of the putative PEREs, cell contraction, and Ca2+ influx. In transgenic mice
      expressing -1058FGFp.luc, a significant three- to sevenfold stimulation of FGF-2
      promoter activity was detected in the hearts of two independent lines 6 h after
      intraperitoneal administration of phenylephrine (50 mg/kg). This increase was
      still apparent at 24 h but was not detected at 48 h posttreatment. Analysis of
      FGF-2 mRNA in normal mouse hearts revealed accumulation of the 6.1-kb transcript
      at 24 h. Control of local FGF-2 synthesis at the transcriptional level through
      adrenergic stimulation may be important in the response to injury as well as in
      the maintenance of a healthy myocardium.

PMID- 10070066
TI  - Effects of beta2-adrenergic stimulation on single-channel gating of rat cardiac L
      type Ca2+ channels.
AB  - Cardiac L-type Ca2+ channels can be stimulated by activation of beta2
      adrenoceptors. We intended to determine how the gating behavior at the single
      channel level (cell-attached configuration) is affected after selective
      stimulation of beta2-adrenoceptors. Rat cardiomyocytes were exposed to zinterol,
      a beta2-agonist (n = 7), isoproterenol (n = 6), a nonselective agonist, 8-bromo
      cAMP (n = 6), and a combination of isoproterenol and ICI-118551 (n = 8), a
      selective beta2-receptor antagonist, or isoproterenol and CGP-20712A, a beta1
      selective antagonist (n = 7). In all groups the ensemble-average current and the
      availability of the channels to open on depolarization were increased in a
      similar fashion. In addition, the open probability (Po) within active sweeps was
      elevated. However, zinterol exerted this effect in a unique manner. It elevated
      Po not by shortening closed times but solely by reducing active sweeps with very
      low Po and a short burst duration. All zinterol effects were abolished by ICI
      118551 (n = 5) and mimicked by isoproterenol plus CGP-20712A (n = 7). We conclude
      that beta2-adrenoceptor activation of L-type channels differs qualitatively from
      the classical cAMP-dependent mechanism.

PMID- 10070067
TI  - Heart rate and behavior of fur seals: implications for measurement of field
      energetics.
AB  - Archival data loggers were used to collect information about depth, swimming
      speed, and heart rate in 23 free-ranging antarctic fur seals. Deployments
      averaged 9.6 +/- 5.6 days (SD) and totaled 191 days of recording. Heart rate
      averaged 108.7 +/- 17.7 beats/min (SD) but varied from 83 to 145 beats/min among
      animals. Morphometrics explained most variations in heart rate among animals.
      These interacted with diving activity and swimming speed to produce a complex
      relationship between heart rate and activity patterns. Heart rate was also
      correlated with behavior over time lags of several hours. There was significant
      (P < 0.05) variation among animals in the degree of diving bradycardia. On
      average, heart rate declined from 100-130 beats/min before the dive to 70-100
      beats/min during submersion. On the basis of the relationship between heart rate
      and rate of oxygen consumption, the overall metabolic rate was 5.46 +/- 1.61 W/kg
      (SD). Energy expenditure appears to be allocated to different activities within
      the metabolic scope of individual animals. This highlights the possibility that
      some activities can be mutually exclusive of one another.

PMID- 10070068
TI  - Neutrophils sense flow-generated stress and direct their migration through
      alphaVbeta3-integrin.
AB  - During inflammation neutrophils are recruited from the blood onto the surface of
      microvascular endothelial cells. In this milieu the presence of soluble
      chemotactic gradients is disallowed by blood flow. However, directional cues are
      still required for neutrophils to migrate to the junctions of endothelial cells
      where extravasation occurs. Shear forces generated by flowing blood provide a
      potential alternative guide. In our flow-based adhesion assay neutrophils
      preferentially migrated in the direction of flow when activated after attachment
      to platelet monolayers. Neutralizing alphaVbeta3-integrin with monoclonal
      antibodies or turning the flow off randomized the direction of migration without
      affecting migration velocity. Purified, immobilized alphaVbeta3-integrin ligands,
      CD31 and fibronectin, could both support flow-directed neutrophil migration in a
      concentration-dependent manner. Migration could be randomized by neutralizing
      alphaVbeta3-integrin interactions with the substrate using antibodies or Arg-Gly
      Asp-containing peptide. These results exemplify mechanical signal transduction
      through integrin-ligand interactions and reveal a guidance system that was
      hitherto unknown in neutrophils. In more general terms, it demonstrates that
      cells can use integrin molecules to "sample" their physical microenvironment
      through adhesion and use this information to modulate their behavior.

PMID- 10070069
TI  - Cyclosporin A treatment alters characteristics of Ca2+-release channel in cardiac
      sarcoplasmic reticulum.
AB  - Chronic treatment with cyclosporin A (CsA) has been reported (H. S. Banijamali,
      M. H. ter Keurs, L. C. Paul, and H. E. ter Keurs. Cardiovasc. Res. 27: 1845-1854,
      1993; I. Kingma, E. Harmsen, H. E. ter Keurs, H. Benediktsson, and L. C. Paul.
      Int. J. Cardiol. 31: 15-22, 1991) to induce reversible alterations of contractile
      properties in rat hearts. To define the molecular mechanisms underlying the
      physiological alterations, the Ca2+-release channel (CRC) and Ca2+-ATPase from
      sarcoplasmic reticulum in rats were examined. Ryanodine binding to whole
      homogenates of rat hearts shows time- and dose-dependent alterations in CRC
      properties by CsA. On 3 wk of treatment with 15 mg CsA. kg body wt-1. day-1, 1)
      maximal ryanodine binding (Bmax) decreased, 2) the dissociation constant of
      ryanodine (Kd) increased, 3) caffeine sensitivity of CRC increased, and 4)
      ruthenium red sensitivity of CRC decreased. On the other hand, Bmax and Kd of
      ryanodine binding in rat skeletal muscles were not changed. Ryanodine-sensitive
      oxalate-supported Ca2+ uptake in whole homogenates was lower in CsA-treated rat
      hearts than in control hearts, whereas total Ca2+ uptake in the presence of 500 M
      ryanodine was not changed. Functional experiments with rapamycin and Western blot
      analysis suggest that the CsA-induced alteration of ryanodine binding is due at
      least in part to an upregulation of calcineurin. The heart muscle-specific
      alterations of CRC could be responsible for the previously reported contractile
      changes of CsA-treated rat hearts.

PMID- 10070070
TI  - Effects of AT1 receptor blockade after myocardial infarct on myocardial fibrosis,
      stiffness, and contractility.
AB  - Angiotensin II type 1 (AT1) receptor blockade attenuates myocardial fibrosis
      after myocardial infarction (MI). However, whether inhibition of fibrosis by AT1
      receptor blockade influences myocardial stiffness and contractility is unknown.
      We measured left ventricular (LV) hemodynamics, papillary muscle function, and
      myocardial stiffness and fibrosis in rats randomized to losartan or placebo 1 day
      after MI and treated subsequently for 8 wk. Losartan decreased LV and right
      ventricular weights as well as mean aortic and LV systolic pressures in sham and
      MI rats. LV end-diastolic pressure increased after MI and was decreased with
      losartan. Maximal developed tension and peak rate of tension rise and decline
      were decreased in MI vs. sham rats. Interstitial fibrosis developed after MI and
      was prevented in losartan-treated MI rats. The development of abnormal myocardial
      stiffness after MI was prevented by losartan. After MI, AT1 receptor blockade
      prevents an abnormal increase in myocardial collagen content. This effect was
      associated with a normalization of passive myocardial stiffness.

PMID- 10070071
TI  - Mapping propagation of mechanical activation in the paced heart with MRI tagging.
AB  - The temporal evolution of three-dimensional (3-D) strain maps derived from
      magnetic resonance imaging (MRI) tagging were used to noninvasively evaluate
      mechanical activation in the left ventricle (LV) while seven canine hearts were
      paced in situ from three different sites: the base of the LV free wall (LVb), the
      right ventricular apex (RVa), and the right atrium (RA). Strain maps plotted
      against time showed the evolution of shortening over the entire LV midwall and
      were used to generate mechanical activation maps showing the onset of
      circumferential shortening. RA pacing showed rapid synchronous shortening; LVb
      pacing showed a wave front of mechanical activation propagating slowly and
      steadily from the pacing site, whereas RVa pacing showed regions of rapid and
      slower propagation. The mechanical (M) activation times correlated linearly with
      the electrical (E) activation (M = 1.06E + 8.4 ms, R = 0.95). The time for 90%
      activation of the LV was 63.1 +/- 24.3 ms for RA pacing, 130.2 +/- 9.8 ms for LVb
      pacing, and 121.3 +/- 17.9 ms for RVa pacing. The velocity of mechanical
      activation was calculated for LVb and RVa pacing and was similar to values
      reported for electrical conduction in myocardium. The propagation of mechanical
      activation for RVa pacing showed regional variations, whereas LVb pacing did not.

PMID- 10070072
TI  - Myocardial creatine kinase kinetics in hearts with postinfarction left
      ventricular remodeling.
AB  - This study examined whether alterations in myocardial creatine kinase (CK)
      kinetics and high-energy phosphate (HEP) levels occur in postinfarction left
      ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19
      pigs 6 wk after myocardial infarction was produced by left circumflex coronary
      artery ligation, and the results were compared with those from 9 normal pigs.
      Blood flow (microspheres), oxygen consumption (MVO2), HEP levels [31P magnetic
      resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in
      myocardium remote from the infarct under basal conditions and during dobutamine
      infusion (20 micrograms. kg-1. min-1 iv). Six of the pigs with LVR had overt
      congestive heart failure (CHF) at the time of study. Under basal conditions,
      creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of
      hearts with CHF and in the subendocardium of LVR hearts than in normal hearts (P
      < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF.
      The CK forward rate constant was lower (P < 0.05) in the CHF group (0.21 +/- 0.03
      s-1) than in LVR (0.38 +/- 0.04 s-1) or normal groups (0.41 +/- 0.03 s-1); CK
      forward flux rates in CHF, LVR, and normal groups were 6.4 +/- 2.3, 14.3 +/- 2.1,
      and 20.3 +/- 2.4 micromol. g-1. s-1, respectively (P < 0.05, CHF vs. LVR and LVR
      vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR
      and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux
      rates did not change during dobutamine in any group. The ratios of CK flux to ATP
      synthesis (from MVO2) under baseline conditions were 10.9 +/- 1.2, 8. 03 +/- 0.9,
      and 3.86 +/- 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05);
      during dobutamine, this ratio decreased to 3.73 +/- 0.5, 2.58 +/- 0.4, and 2.78
      +/- 0.5, respectively (P = not significant among groups). These data demonstrate
      that CK flux rates are decreased in hearts with postinfarction LVR, but this
      change does not limit the response to dobutamine. In hearts with end-stage CHF,
      the changes in HEP and CK flux are more marked. These changes could contribute to
      the decreased responsiveness of these hearts to dobutamine.

PMID- 10070073
TI  - Constitutive expression of interleukin-1alpha precursor promotes human vascular
      smooth muscle cell proliferation.
AB  - Vascular smooth muscle cell (VSMC) proliferation plays a critical role in the
      failure of vascular surgeries and contributes to the development of
      atherosclerotic lesions. Evidence that interleukin-1 (IL-1) is a mitogen for
      cultured VSMC has implicated its release by activated macrophages in the
      development of atherosclerosis. VSMC also produce IL-1, including the precursor
      form of IL-1alpha. However, it is not known whether IL-1alpha precursor is
      processed to mature IL-1alpha or released from VSMC, nor is it known whether
      either precursor or mature IL-1alpha functions as an autocrine growth factor. The
      goals of the present study were to establish whether proliferation is enhanced in
      human VSMC transfectants producing IL-1alpha constitutively at levels comparable
      to those produced after activation, and to determine which domains of IL-1alpha
      are important for its activity. Human VSMC were stably transfected with
      expression vectors directing constitutive expression of either full-length IL
      1alpha precursor [IL-1alpha-(1-271)], its NH2-terminal domain [IL-1alpha-(1
      112)], or mature IL-1alpha [IL-1alpha-(113-271)]. Both IL-1alpha-(1-271) and IL
      1alpha-(113-271) stable transfectants produced moderate levels of IL-1alpha (0.2
      1.0 ng/10(6) cells) and released low levels of IL-1alpha into the supernatant
      (<20 pg/ml). VSMC stably transfected with either IL-1alpha-(1-271) or IL-1alpha
      (113-271) expression plasmids proliferated rapidly compared with nontransfected
      or vector-transfected VSMC and displayed a distinct morphology characterized by
      elongated, spindle-shaped cells. Stable transfection with IL-1alpha-(1-271) was
      somewhat more effective than transfection with IL-1alpha-(113-271).
      Interestingly, VSMC transfected with IL-1alpha-(113-271) expression plasmids also
      expressed IL-1alpha-(1-271) mRNA, suggesting that IL-1alpha-(113-271) activates
      an IL-1-induced IL-1 autocrine loop. In contrast, neither proliferation rates nor
      morphology was affected by stable transfection with IL-1alpha-(1-112) expression
      plasmids. Exogenous IL-1 receptor antagonist partially reversed the enhanced DNA
      synthesis in VSMC transfected with either IL-1alpha-(1-271) or IL-1alpha-(113
      271) expression plasmids, suggesting that the pro-proliferative effect of VSMC
      derived IL-1alpha is at least partially mediated by signaling via the type I IL-1
      receptor. These results demonstrate that IL-1alpha precursor is an autocrine
      growth factor for human VSMC and further indicate that amino acids 113-271 play a
      crucial role in its actions.

PMID- 10070074
TI  - Peripheral muscle ergoreceptors and ventilatory response during exercise recovery
      in heart failure.
AB  - Recent studies have suggested that the increased ventilatory response during
      exercise in patients with chronic heart failure was related to the activation of
      muscle metaboreceptors. To address this issue, 23 patients with heart failure and
      7 normal subjects performed arm and leg bicycle exercises with and without cuff
      inflation around the arms or the thighs during recovery. Obstruction slightly
      reduced ventilation and gas exchange variables at recovery but did not change the
      kinetics of recovery of these parameters compared with nonobstructed recovery:
      half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and
      155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not
      significant within each group from baseline to obstructed recovery). We conclude
      that muscle metaboreceptor activation does not seem to play a role in the
      exertion hyperventilation of patients with heart failure.

PMID- 10070075
TI  - Nitric oxide mediates sympathetic vasoconstriction at supraspinal, spinal, and
      synaptic levels.
AB  - The purposes of this study were to investigate the level of the sympathetic
      nervous system in which nitric oxide (NO) mediates regional sympathetic
      vasoconstriction and to determine whether neural mechanisms are involved in
      vasoconstriction after NO inhibition. Ganglionic blockade (hexamethonium), alpha1
      receptor blockade (prazosin), and spinal section at T1 were used to study
      sympathetic involvement. NO was blocked with Nomega-nitro-L-arginine methyl ester
      (L-NAME). Regional blood flow in the mesenteric and renal arteries and terminal
      aorta was monitored by electromagnetic flowmetry in conscious rats. L-NAME (3-5
      mg/kg iv) increased arterial pressure and peripheral resistance. Ganglionic
      blockade (25 mg/kg iv) significantly reduced the increase in resistance in the
      mesentery and kidney in intact and spinal-sectioned rats. Ganglionic blockade
      significantly decreased hindquarter resistance in intact rats but not in spinal
      sectioned rats. Prazosin (200 micrograms/kg iv) significantly reduced the
      increased hindquarter resistance. We concluded that NO suppresses sympathetic
      vasoconstriction in the mesentery and kidney at the spinal level, whereas
      hindquarter tone is mediated at supraspinal and synaptic levels.

PMID- 10070076
TI  - Estrogen increases Ca2+ efflux from female porcine coronary arterial smooth
      muscle.
AB  - Acute estrogen administration relaxes vascular smooth muscle by decreasing
      intracellular Ca2+ concentration ([Ca2+]i). In the present study, we examined the
      hypothesis that this reduction in [Ca2+]i is mediated in part by enhanced Ca2+
      efflux. Coronary artery smooth muscle cells were isolated from gonad-intact,
      sexually mature female pigs. The [Ca2+]i response to endothelin-1 was measured
      using fluo 3 and confocal microscopy. 17beta-Estradiol (E2beta), but not 17alpha
      estradiol or triamcinolone acetonide, caused a concentration-dependent (IC50 = 10
      nM) decrease in the [Ca2+]i response to endothelin-1. This decrease was blocked
      by the specific estrogen receptor antagonist ICI-182780. Under conditions in
      which Ca2+ influx and sarcoplasmic reticulum Ca2+ reuptake were blocked, E2beta
      still decreased [Ca2+]i. The response was blocked by extracellular lanthanum.
      These data indicate that E2beta decreases [Ca2+]i in coronary artery smooth
      muscle by affecting Ca2+ efflux via a receptor-mediated mechanism.

PMID- 10070077
TI  - Formation of 4-hydroxy-2-nonenal-modified proteins in ischemic rat heart.
AB  - 4-Hydroxy-2-nonenal (HNE) is a major lipid peroxidation product formed during
      oxidative stress. Because of its reactivity with nucleophilic compounds,
      particularly metabolites and proteins containing thiol groups, HNE is cytotoxic.
      The aim of this study was to assess the extent and time course for the formation
      of HNE-modified proteins during ischemia and ischemia plus reperfusion in
      isolated rat hearts. With an antibody to HNE-Cys/His/Lys and densitometry of
      Western blots, we quantified the amount of HNE-protein adduct in the heart. By
      taking biopsies from single hearts (n = 5) at various times (0, 5, 10, 15, 20,
      35, and 40 min) after onset of zero-flow global ischemia, we showed a
      progressive, time-dependent increase (which peaked after 30 min) in HNE-mediated
      modification of a discrete number of proteins. In studies with individual hearts
      (n = 4/group), control aerobic perfusion (70 min) resulted in a very low level
      (296 arbitrary units) of HNE-protein adduct formation; by contrast, after 30-min
      ischemia HNE-adduct content increased by >50-fold (15,356 units, P < 0.05). In
      other studies (n = 4/group), administration of N-(2-mercaptopropionyl)glycine
      (MPG, 1 mM) to the heart for 5 min immediately before 30-min ischemia reduced HNE
      protein adduct formation during ischemia by approximately 75%. In studies (n =
      4/group) that included reperfusion of hearts after 5, 10, 15, or 30 min of
      ischemia, there was no further increase in the extent of HNE-protein adduct
      formation over that seen with ischemia alone. Similarly, in experiments with MPG,
      reperfusion did not significantly influence the tissue content of HNE-protein
      adduct. Western immunoblot results were confirmed in studies using in situ
      immunofluorescent localization of HNE-protein in cryosections. In conclusion,
      ischemia causes a major increase in HNE-protein adduct that would be expected to
      reflect a toxic sequence of events that might act to compromise tissue survival
      during ischemia and recovery on reperfusion.

PMID- 10070078
TI  - 5-HT2B-receptor antagonist LY-272015 is antihypertensive in DOCA-salt
      hypertensive rats.
AB  - We previously demonstrated a change in the receptors mediating 5
      hydroxytryptamine (5-HT)-induced contraction in arteries of deoxycorticosterone
      acetate (DOCA)-salt-hypertensive rats. Specifically, contraction to 5-HT is
      mediated primarily by 5-HT2A receptors in arteries from normotensive sham rats
      and by both 5-HT2A and 5-HT2B receptors in arteries from hypertensive rats. We
      hypothesized that the 5-HT2B receptor may play a role in maintaining the high
      blood pressure of DOCA-salt-hypertensive rats, and herein we provide data
      connecting in vitro and in vivo findings. The endothelium-denuded isolated
      superior mesenteric artery of DOCA-salt rats displayed a marked increase in
      maximum contraction to the newly available 5-HT2B-receptor agonist BW-723C86
      compared with that of arteries from sham rats, confirming that the 5-HT2B
      receptor plays a greater role in 5-HT-induced contraction in arteries from DOCA
      salt rats. In chronically instrumented rats, the 5-HT2B-receptor antagonist LY
      272015 (0.3, 1.0, and 3.0 mg/kg iv at 30-min intervals) was given cumulatively 1
      time/wk during 4 wk of continued DOCA-salt treatment. LY-272015 did not reduce
      blood pressure of the sham-treated rats at any time or dose. However, LY-272015
      (1.0 and 3. 0 mg/kg) significantly reduced mean blood pressure in a subgroup of
      week 3 (-20 mmHg) and week 4 DOCA-salt (-40 mmHg) rats that had extremely high
      blood pressure (mean arterial blood pressure approximately 200 mmHg). Blockade of
      5-HT2B receptors by in vivo administration of LY-272015 (3.0 mg/kg) was verified
      by observing reduced 5-HT-induced contraction in rat stomach fundus, the tissue
      from which the 5-HT2B receptor was originally cloned. These data support the
      novel hypothesis that 5-HT2B-receptor expression is induced during the
      development of DOCA-salt hypertension and contributes to the maintenance of
      severe blood pressure elevations.

PMID- 10070079
TI  - Modulation of AV nodal and Hisian conduction by changes in extracellular space.
AB  - Previous studies have demonstrated that the extracellular space (ECS) component
      of the atrioventricular (AV) node and His bundle region is larger than the ECS in
      adjacent contractile myocardium. The potential physiological significance of this
      observation was examined in a canine blood-perfused AV nodal preparation.
      Mannitol, an ECS osmotic expander, was infused directly into either the AV node
      or His bundle region. This resulted in a significant dose-dependent increase in
      the AV nodal or His-ventricular conduction time and in the AV nodal effective
      refractory period. Mannitol infusion eventually resulted in Wenckebach block (n =
      6), which reversed with mannitol washout. The ratio of AV nodal to left
      ventricular ECS in tissue frozen immediately on the development of heart block (n
      = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared
      with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog
      hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower
      mannitol rates (10% of total blood flow), AV nodal conduction times increased by
      5-10% and the AV node became supersensitive to adenosine, acetylcholine, and
      carbachol, but not to norepinephrine. We conclude that mannitol-induced changes
      in AV node and His bundle ECS markedly alter conduction system electrophysiology
      and the sensitivity of conductive tissues to purinergic and cholinergic agonists.

PMID- 10070080
TI  - Gender differences in coronary artery diameter reflect changes in both
      endothelial Ca2+ and ecNOS activity.
AB  - Elevation of nitric oxide (NO) release from the vascular endothelium may
      contribute to some of the gender-associated differences in coronary artery
      function. The mechanisms by which gender affects NO release from the endothelium
      of coronary arteries are not known. In this study, endothelial function was
      examined in pressurized coronary arteries from female and male rats. Diameter and
      endothelial cell intracellular Ca2+ concentration ([Ca2+]i) in intact arteries,
      as well as enzymatic activity of endothelial constitutive nitric oxide synthase
      (ecNOS) in arterial lysates, was measured. Elevation of intravascular pressure to
      60 mmHg constricted coronary arteries from female animals less than coronary
      arteries from male animals (18% and 31% constriction, respectively). The
      increased arterial diameter of coronary arteries from females was associated with
      elevated endothelial [Ca2+]i (female 174 nM, male 90 nM; P < 0.001). Elevation of
      Ca2+ activated ecNOS with a similar slope and half-activation constant (
      approximately 160 nM) for both female and male coronary arteries. However, at
      [Ca2+] > 100 nM, ecNOS activity was significantly higher in coronary arteries
      from female rats compared with their male equivalents (P < 0.01). Maximal
      activity for ecNOS at saturating Ca2+ (300 nM) was 37% higher in coronary
      arteries from female animals compared with male animals (P < 0.05). Thus elevated
      [Ca2+]i in the endothelium of female coronary arteries alone is predicted to
      increase the production of NO (by nearly 2-fold). This gender difference combined
      with increased ecNOS activity at a given [Ca2+] in females indicates that tonic
      NO production should be nearly threefold greater in female coronary arteries
      compared with male coronary arteries. We conclude that, in the regulation of
      endothelial Ca2+ and ecNOS, gender differences contribute significantly to the
      overall decrease in myogenic tone observed in coronary arteries of females.

PMID- 10070081
TI  - Hypotension induced by exercise is associated with enhanced release of adenyl
      purines from aged rat artery.
AB  - To determine whether the antihypertensive effects of exercise are associated with
      release of ATP and its metabolites from arteries, we assayed blood pressure and
      the release of adenine nucleotides and nucleosides from the caudal arteries of
      exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill
      for 12 wk significantly decreased the rise in systolic and diastolic blood
      pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of
      oleic, linoleic, and linolenic acids in the caudal artery decreased significantly
      with exercise, demonstrating an association between exercise and the unsaturation
      index of caudal arterial fatty acids. The amounts of total adenyl purines
      released by the arterial segments from exercised rats, both spontaneously and in
      response to norepinephrine, were significantly greater by 80.0 and 60.7%,
      respectively, than those released by tissues from sedentary rats. These results
      suggest that exercise alters the membrane fatty acid composition in aged rats as
      well as the release of ATP from vascular endothelial cells and that these factors
      are associated with the regression of the rise in blood pressure normally
      observed with advanced age.

PMID- 10070082
TI  - Epidermal growth factor: a potent vasoconstrictor in experimental hypertension.
AB  - We have tested the hypothesis that growth factor signaling pathways are augmented
      in hypertension, a disease associated with vascular smooth muscle cell growth.
      Thoracic aorta was dissected from deoxycorticosterone acetate-salt (DOCA-salt)
      and one kidney, one clip (1K, 1C) hypertensive rats and from sham normotensive
      rats for use in isolated tissue bath experiments. Systolic blood pressure was
      significantly higher in DOCA-salt and 1K, 1C than in normotensive sham rats: 192
      +/- 7, 185 +/- 10, and 117 +/- 4 mmHg, respectively. Although virtually no
      contraction to epidermal growth factor (EGF) was observed in endothelium-denuded
      sham rat aorta [1 +/- 1% phenylephrine (PE) (10 micromol/l)-induced contraction],
      the maximal EGF-induced contraction was 45 +/- 7% in endothelium-denuded aorta
      from DOCA-salt hypertensive rats and 39 +/- 7% in aorta from 1K, 1C rats.
      Although slightly attenuated, a contraction to EGF was still observed in
      endothelium-intact aortic strips from 28-day DOCA-salt hypertensive rats. We also
      conducted concentration-response curves to EGF on days 1, 3, 5, 7, 14, and 21 of
      DOCA-salt therapy. A significant contraction to EGF in aorta from DOCA-salt rats
      was observed on day 14, when DOCA-salt rats had significantly higher blood
      pressure than sham rats: 188 +/- 6 and 122 +/- 3 mmHg, respectively. Transforming
      growth factor-alpha, an agonist of the EGF receptor, contracted DOCA-salt rat
      aorta (30 +/- 7% PE-induced contraction) but not sham aorta (3 +/- 3%). The EGF
      receptor tyrosine kinase inhibitor 4,5-dianilinophthalimide (10 micromol/l), the
      mitogen-activated protein kinase kinase inhibitor PD-098059 (10 micromol/l), and
      the L-type voltage-gated calcium channel inhibitor diltiazem (1 mol/l), but not
      the cyclooxygenase inhibitor indomethacin (10 micromol/l), virtually abolished
      EGF-induced contraction (85, 98, and 99% reduction, respectively). These data
      support a striking difference in EGF signaling between normotensive and
      hypertensive animals. Furthermore, they provide evidence that growth factors
      should be considered vasoconstrictors as well as growth modulators in
      hypertension.

PMID- 10070083
TI  - Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in
      the rat.
AB  - Studies were conducted with rats to investigate whether exposure to CO at
      concentrations frequently found in the environment caused nitric oxide (NO)
      mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per
      million or higher for 1 h increased the concentration of nitrotyrosine in the
      aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion
      along the endothelial lining, and this was inhibited by pretreatment with the NO
      synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). The CO
      induced elevations of aortic nitrotyrosine were not altered by neutropenia or
      thrombocytopenia, and CO caused no change in the concentration of endothelial
      NOS. Consequences from NO-derived stress on the vasculature included an enhanced
      transcapillary efflux of albumin within the first 3 h after CO exposure and
      leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized
      plasma low-density lipoprotein was found immediately after CO exposure, but this
      was not inhibited by L-NAME pretreatment. We conclude that exposure to relatively
      low CO concentrations can alter vascular status by several mechanisms and that
      many changes are linked to NO-derived oxidants.

PMID- 10070084
TI  - Metallothionein inhibits ischemia-reperfusion injury in mouse heart.
AB  - Oxidative stress is believed to play a major role in ischemia-reperfusion injury
      to the heart. Metallothionein (MT), a potential free radical scavenger, may
      function in cardiac protection against ischemia-reperfusion damage. To test this
      hypothesis, a specific cardiac MT-overexpressing transgenic mouse model was used.
      The hearts isolated from these animals were subjected to 50 min of warm (37
      degrees C) zero-flow ischemia followed by 60- or 90-min reflow. Compared with the
      nontransgenic controls, the transgenic mouse hearts with MT concentrations
      approximately 10-fold higher than normal showed significantly improved recovery
      of contractile force postischemia (69.2 +/- 4.2 vs. 26.0 +/- 6.0% at the end of
      60-min reperfusion, P < 0.01). Efflux of creatine kinase from these transgenic
      hearts was reduced by more than 50% (P < 0.01). In addition, the zone of
      infarction induced by ischemia-reperfusion at the end of 90-min reperfusion was
      suppressed by approximately 40% (P < 0.01) in the transgenic hearts. The results
      strongly indicate that MT provides protection against ischemia-reperfusion
      induced heart injury.

PMID- 10070085
TI  - Regulation of energy consumption in cardiac muscle: analysis of isometric
      contractions.
AB  - The well-known linear relationship between oxygen consumption and force-length
      area or the force-time integral is analyzed here for isometric contractions. The
      analysis, which is based on a biochemical model that couples calcium kinetics
      with cross-bridge cycling, indicates that the change in the number of force
      generating cross bridges with the change in the sarcomere length depends on the
      force generated by the cross bridges. This positive-feedback phenomenon is
      consistent with our reported cooperativity mechanism, whereby the affinity of the
      troponin for calcium and, hence, cross-bridge recruitment depends on the number
      of force-generating cross bridges. Moreover, it is demonstrated that a model that
      does not include a feedback mechanism cannot describe the dependence of energy
      consumption on the loading conditions. The cooperativity mechanism, which has
      been shown to determine the force-length relationship and the related Frank
      Starling law, is shown here to provide the basis for the regulation of energy
      consumption in the cardiac muscle.

PMID- 10070086
TI  - Conducted signals within arteriolar networks initiated by bioactive amino acids.
AB  - Our purpose was to determine the specificity of L-arginine (L-Arg)-induced
      conducted signals for intra- vs. extracellular actions of L-Arg. Diameter and red
      blood cell velocities were measured for arterioles [18 +/- 1.6 (SE) micrometer]
      in the cremaster muscle of pentobarbital sodium-anesthetized (Nembutal, 70 mg/kg)
      hamsters (n = 53). Remote (conducted) responses were viewed approximately 1,000
      micrometer upstream from the local (micropipette) application. Six amino acids
      were tested: L-arginine, L-cystine, L-leucine, L-lysine, L-histidine, and L
      aspartate (100 microM each). Only L-Arg induced a remote dilation; L-lysine and L
      aspartate had no effect, and the others each induced a significant remote
      constriction. There is a second conducted signal initiated by L-arginine that
      preconditions the arteriolar network and upregulates a direct response of L
      arginine to dilate the remote site. This was blocked by inhibition of L-arginine
      uptake at the local (preconditioning) site (100 microM L-histidine or 1 mM
      phenformin). Arginine-glycine-aspartate (100 microM)-induced remote dilations
      (+3. 2 +/- 0.3 micrometer) were not mimicked by a peptide control and were
      prevented by anti- integrin alphav monoclonal antibody. Remote dilations were
      greater in animals with a higher wall shear stress for arginine-glycine-aspartate
      (r2 = 0.92) but not for L-arginine (r2 = 0.12). Thus L-arginine initiates
      separate conducted signals related to system y+ transport, integrins, and
      baseline flow.

PMID- 10070087
TI  - Maintenance of blood pressure in normotensive dogs by endothelin.
AB  - The role of endothelin (ET)-1 in blood pressure homeostasis and the interaction
      with the renin-angiotensin system (RAS) was investigated in normotensive
      conscious dogs. ETA receptors were blocked by LU-135252 (1-30 mg/kg);
      trandolapril (2 mg/kg) or losartan (10 mg/kg) was used to inhibit the RAS. LU
      135252 in oral doses of 3-30 mg/kg significantly reduced mean arterial pressure
      (MAP) by approximately 10 mmHg maximally, whereas trandolapril or losartan were
      without any effect. MAP reduction was more pronounced when LU-135252 was combined
      with either losartan (-15.5 +/- 3.2 mmHg; 2 h postadministration; P < 0.05) or
      trandolapril (-30.9 +/- 3.6 mmHg; P < 0.05). When endogenous nitric oxide (NO)
      generation was blocked but NO concomitantly infused, this synergistic effect on
      MAP was prevented. The data show that ET-1 contributes to the maintenance of
      blood pressure via ETA receptors. Furthermore, ET-1 and ANG II play a prominent
      role in the control of blood pressure by opposing the effects of NO. The
      pronounced blood pressure fall after combined blockade of ETA receptors and the
      RAS may be mediated by an enhanced release of NO.

PMID- 10070088
TI  - Endothelin antagonists block alpha1-adrenergic constriction of coronary
      arterioles.
AB  - We have previously observed that intracoronary administration of the alpha1
      adrenergic agonist phenylephrine (PE) over a period of minutes induced both an
      immediate and long-lasting (2 h) vasoconstriction of epicardial coronary
      arterioles. Because it is unlikely that alpha1-adrenergic constriction would
      persist for hours after removal of the agonist, this observation supports the
      view that another constrictor(s) is released during alpha1-adrenergic activation
      and induces the prolonged vasoconstriction. Therefore, we hypothesized that the
      prolonged microvascular constriction after PE is due to the production of
      endothelin (ET). We focused on ET not only because this peptide produces potent
      vasoconstriction but also because its vasoconstrictor action is characterized by
      a long duration. To test this hypothesis, the diameters of coronary arterioles
      (<222 micrometers) in the beating heart of pentobarbital-anesthetized dogs with
      stroboscopic intravital microscopy were measured during a 15-min intracoronary
      infusion of PE (1 microgram. kg-1 . min-1) and at 15-min intervals for a total of
      120 min. All experiments were performed in the presence of beta-adrenergic
      blockade with propranolol. At 120 min, arterioles in the PE group were
      constricted (-23 +/- 9% change in diameter vs. baseline). Pretreatment with the
      ET-converting enzyme inhibitor phosphoramidon or the ETA-receptor antagonist FR
      139317 prevented the PE-induced constriction at 120 min (-1 +/- 3 and -6 +/- 3%,
      respectively, P < 0.01 vs. PE). Pretreatment with the selective alpha1-adrenergic
      antagonist prazosin (Prz) also prevented the sustained constriction (0 +/- 2%, P
      < 0.01 vs. PE) but Prz given 60 min after PE infusion did not (-13 +/- 3%). In
      the aggregate, these results show that vasoconstriction of epicardial coronary
      arterioles via alpha1-adrenergic activation is blocked by an ET antagonist and an
      inhibitor of its production. From these data, we conclude that alpha1-adrenergic
      activation promotes the production and/or release of ET, which produces or
      facilitates microvascular constriction of epicardial canine coronary arterioles.

PMID- 10070089
TI  - Interstitial Ca2+ undergoes dynamic changes sufficient to stimulate nerve
      dependent Ca2+-induced relaxation.
AB  - We recently described a perivascular sensory nerve-linked dilator system that can
      be activated by interstitial Ca2+ (Ca2+isf). The present study tested the
      hypothesis that Ca2+isf in the rat duodenal submucosa varies through a range that
      is sufficient to activate this pathway. An in situ microdialysis method was used
      to estimate Ca2+isf. When the duodenal lumen was perfused with Ca2+-free buffer,
      Ca2+isf was 1.0 +/- 0.13 mmol/l. Ca2+isf increased to 1.52 +/- 0.04, 1.78 +/-
      0.10, and 1.89 +/- 0.1 when the lumen was perfused with buffer containing 3, 6,
      and 10 mmol/l Ca2+, respectively (P < 0.05). Ca2+isf was 1.1 +/- 0.06 mmol/l in
      fasted animals and increased to 1. 4 +/- 0.06 mmol/l in free-feeding rats (P <
      0.05). Wire myography was used to study isometric tension responses of isolated
      mesenteric resistance arteries. Cumulative addition of extracellular Ca2+-relaxed
      serotonin- and methoxamine-precontracted arteries with half-maximal effective
      doses of 1.54 +/- 0.05 and 1.67 +/- 0.08 mmol/l, respectively (n = 5). These data
      show that duodenal Ca2+isf undergoes dynamic changes over a range that activates
      the sensory nerve-linked dilator system and indicate that this system can link
      changes in local Ca2+ transport with alterations in regional resistance and organ
      blood flow.

PMID- 10070090
TI  - Inhibition of copper/zinc superoxide dismutase impairs NO.-mediated endothelium
      dependent relaxations.
AB  - The superoxide anion (O-2.) appears to be an important modulator of nitric oxide
      (NO.) bioavailability. The present study was designed to characterize the role of
      copper/zinc superoxide dismutase (Cu/Zn SOD) in endothelium-dependent
      relaxations. Cu/Zn SOD was inhibited with the Cu2+ chelator diethyldithiocarbamic
      acid (DETCA). In isolated canine basilar arteries, DETCA (7.6 x 10(-3) M)
      inhibited total vascular SOD activity by 46% (P < 0.0001, n = 6-8 dogs). DETCA
      (7.6 x 10(-3) M) significantly reduced relaxations to bradykinin and A-23187 (P <
      0.05, n = 7-11). The inhibitory effect of DETCA was abolished by the O-2.
      scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron; 9.4 x 10(-3) M; P <
      0.05, n = 6-13). Tiron significantly potentiated the relaxations to bradykinin in
      control rings (P < 0.05, n = 13), and the nitric oxide synthase inhibitor Nomega
      nitro-L-arginine methyl ester (L-NAME; 3 x 10(-4) M) abolished these relaxations
      (P < 0.0001, n = 6). DETCA and Tiron had no effect on the relaxations to
      diethylamine-NONOate or forskolin (P > 0.05, n = 6). Our results demonstrate that
      endothelium-dependent relaxations mediated by NO. are impaired after the
      inhibition of Cu/Zn SOD. Relaxations to bradykinin (but not A-23187) were
      significantly augmented by Tiron. Pharmacological scavenging of O-2. reverses the
      effect of Cu/Zn SOD inhibition.

PMID- 10070091
TI  - Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance
      and resistance arteries.
AB  - Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventricular
      myocytes, may influence coronary vascular tone. We studied the coronary
      vasodilatory response to BNP under physiological conditions and after
      preconstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-flow
      velocity (APV) was measured using intracoronary Doppler, and cross-sectional area
      (CSA) was measured using intravascular ultrasound. Coronary blood flow (CBF) was
      calculated. Intracoronary BNP induced dose-dependent increases in CSA, APV, and
      CBF similar in magnitude to those induced by nitroglycerin (NTG). The magnitude
      of BNP-induced vasodilation was accentuated after preconstriction with ET-1.
      Pretreatment with either the nitric oxide synthase inhibitor Nomega-nitro-L
      arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the
      coronary vasodilator effect of BNP in resistance arteries without influencing
      epicardial vasodilation. Pretreatment with the ATP-sensitive potassium-channel
      blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We
      conclude that BNP exerts coronary vasodilator effects, predominantly in
      epicardial conductance vessels. An accentuated vasodilatory response to BNP
      occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary
      resistance arteries may be partially mediated via nitric oxide and/or
      prostaglandin release.

PMID- 10070092
TI  - Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary
      arterioles.
AB  - The purpose of this study was to test the hypothesis that increased flow through
      coronary arterioles increases endothelial cell nitric oxide synthase (ecNOS) and
      Cu/Zn superoxide dismutase (SOD) mRNA expression. Single porcine coronary
      arterioles (ID 100-160 micrometers; pressurized) were cannulated, perfused, and
      exposed to intraluminal flow sufficient to produce maximal flow-induced dilation
      of coronary arterioles (high flow; 7.52 +/- 0.22 microliter/min), low flow (0.84
      +/- 0.05 microliter/min), or no flow for 2 or 4 h. Mean shear stress was
      calculated to be 5.7 +/- 1.0 dyn/cm2 for high-flow arterioles and 1. 6 +/- 1.0
      dyn/cm2 for low-flow arterioles. At the end of the treatment period, mRNA was
      isolated from each vessel, and ecNOS and SOD mRNA expression was assessed using a
      semiquantitative RT-PCR. All data were standardized by coamplifying ecNOS or SOD
      with glyceraldehyde-3-phosphate dehydrogenase. The results indicate that ecNOS
      mRNA expression is increased in arterioles exposed to 2 or 4 h of high flow. In
      contrast, SOD mRNA expression was increased only after 4 h of high flow. Neither
      gene is induced by exposure to low flow. On the basis of these data, we concluded
      that ecNOS and SOD mRNA expression is regulated by flow in porcine coronary
      arterioles. In addition, we concluded that a threshold level of flow and shear
      stress must be sustained to elicit the upregulation of ecNOS and SOD mRNA
      expression.

PMID- 10070093
TI  - Contribution of L-type Ca2+ current to electrical activity in sinoatrial nodal
      myocytes of rabbits.
AB  - The role of L-type calcium current (ICa,L) in impulse generation was studied in
      single sinoatrial nodal myocytes of the rabbit, with the use of the amphotericin
      perforated patch-clamp technique. Nifedipine, at a concentration of 5 microM, was
      used to block ICa,L. At this concentration, nifedipine selectively blocked ICa,L
      for 81% without affecting the T-type calcium current (ICa,T), the fast sodium
      current, the delayed rectifier current (IK), and the hyperpolarization-activated
      inward current. Furthermore, we did not observe the sustained inward current. The
      selective action of nifedipine on ICa,L enabled us to determine the activation
      threshold of ICa,L, which was around -60 mV. As nifedipine (5 microM) abolished
      spontaneous activity, we used a combined voltage- and current-clamp protocol to
      study the effects of ICa,L blockade on repolarization and diastolic
      depolarization. This protocol mimics the action potential such that the
      repolarization and subsequent diastolic depolarization are studied in current
      clamp conditions. Nifedipine significantly decreased action potential duration at
      50% repolarization and reduced diastolic depolarization rate over the entire
      diastole. Evidence was found that recovery from inactivation of ICa,L occurs
      during repolarization, which makes ICa,L available already early in diastole. We
      conclude that ICa,L contributes significantly to the net inward current during
      diastole and can modulate the entire diastolic depolarization.

PMID- 10070094
TI  - Aortic pressure-diameter relationship assessed by intravascular ultrasound:
      experimental validation in dogs.
AB  - Intravascular ultrasound (IVUS) has emerged as an important diagnostic method for
      evaluating vessel diameter and vessel wall motion. To evaluate the validity of
      IVUS in assessing changes in the pressure-diameter relationship we compared
      measurements of abdominal aortic diameters derived from IVUS with those
      simultaneously obtained at the same site using implanted sonomicrometers in five
      chronically instrumented conscious dogs and in seven acutely instrumented
      anesthetized dogs. Five hundred eighty beats were analyzed to obtain peak
      systolic and end-diastolic diameters and to calculate aortic compliance at
      different blood pressure levels induced either by an aortic pneumatic cuff or by
      intravenous injections of nitroglycerin or norepinephrine. IVUS agreed closely
      with sonomicrometer measurements at different blood pressure levels. However,
      IVUS slightly but significantly underestimated aortic diameters by 0.6 +/- 0.7 mm
      for systolic diameters (P < 0.001) and by 0.7 +/- 0.6 mm for diastolic diameters
      (P < 0.001) compared with the sonomicrometer measurements. We conclude that IVUS
      is a feasible and reliable method to measure dynamic changes in aortic dimensions
      and has the potential to provide ready access to assess aortic compliance in
      humans.

PMID- 10070095
TI  - A method for collecting right coronary venous blood samples from conscious dogs.
AB  - This report describes for the first time a technique to collect right coronary
      venous blood samples from conscious dogs. Catheters, prepared from Micro
      Renathane tubing, were surgically implanted in right ventricular superficial
      veins of three anesthetized dogs. Also implanted were an arterial catheter, a
      right coronary flow transducer, and a right coronary artery constrictor. The
      coronary catheter was introduced at a venous bifurcation so that its side holes
      were positioned above the bifurcation; both ends of the catheter were
      exteriorized. Heparinized saline was continuously infused through the venous
      catheter by a battery-powered pump. The dogs were maintained for 10-13 days after
      surgery, and all catheters remained patent. Multiple right coronary venous
      samples were collected from each dog. These samples were analyzed for venous
      oxygen tension (PvO2) under baseline conditions, with right coronary pressure
      reduced to 50 mmHg, and during the reactive hyperemia after release of the right
      coronary artery constriction. PvO2 was 27.7 +/- 1.0 mmHg at baseline, 23.4 +/-
      1.0 mmHg during coronary artery constriction, and 34.3 +/- 1.5 mmHg during
      reactive hyperemia. These data and the position of the catheter at autopsy
      demonstrated that coronary venous blood had been sampled.

PMID- 10070096
TI  - Chemotactic, mitogenic, and angiogenic actions of UTP on vascular endothelial
      cells.
AB  - Endothelial cells express receptors for ATP and UTP, and both UTP and ATP elicit
      endothelial release of vasoactive compounds such as prostacyclin and nitric
      oxide; however, the distinction between purine and pyrimidine nucleotide
      signaling is not known. We hypothesized that UTP plays a more important role in
      endothelial mitogenesis and chemotaxis than does ATP and that UTP is angiogenic.
      In cultured endothelial cells from guinea pig cardiac vasculature (CEC), both UTP
      and vascular endothelial growth factor (VEGF) were significant mitogenic and
      chemotactic factors; in contrast, ATP demonstrated no significant chemotaxis in
      CEC. In chick chorioallantoic membranes (CAM), UTP and VEGF treatments produced
      statistically significant increases in CAM vascularity compared with controls.
      These findings are the first evidence of chemotactic or angiogenic effects of
      pyrimidines; they suggest a role for pyrimidine nucleotides that is distinct from
      those assumed by purine nucleotides and provide for the possibility that UTP
      serves as an extracellular signal for processes such as endothelial repair and
      angiogenesis.

PMID- 10070097
TI  - Acute exercise can improve cardioprotection without increasing heat shock protein
      content.
AB  - The aim of this study was to determine the effects of acute bouts of exercise on
      myocardial recovery after ischemia and heat shock protein expression. Adult
      female Sprague-Dawley rats were divided into five groups: 1) 1-day run (1DR; n =
      6) and 2) 3-day run (3DR; n = 7), in which rats ran for 100 min at a speed of 20
      m/min up a 6 degrees grade for 1 or 3 consecutive days; 3) 1-day cold run (1CR),
      in which rats ran the same as 1DR but with wet fur at 8 degrees C, which
      prevented an elevation of core temperature (n = 8); 4) heat shock sedentary (HS),
      in which rats had their core temperatures raised to 42 degrees C one time for 15
      min (n = 5); and 5) sedentary control (n=15). Cardiac function was analyzed 24 h
      after the last treatment using an isolated, working heart model. Nonpaced hearts
      were initially perfused under normoxic conditions, then underwent 17 min of
      global, normothermic (37 degrees C) ischemia, and, finally, were allowed to
      recover for 30 min under normoxic conditions. The concentration of the 72-kDa
      heat shock protein (HSP 72) was measured in each left ventricle. Compared with
      that in the sedentary group, recovery of cardiac output x systolic pressure (CO x
      SP) was enhanced (P < 0.05) in all treatment groups when the postischemic value
      was covaried with the preischemic value. No differences in CO x SP were found (P
      > 0.05) between the following groups: 1DR vs. 3DR, 1DR vs. HS, and 1DR vs. 1CR.
      Heat shock protein concentration was significantly greater (P < 0.05) than that
      in the sedentary controls in HS, 1DR, and 3DR groups, but not for 1CR. The
      concentration of HSP 72 was not significantly correlated with postischemic CO x
      SP (R2 = 0.197, P > 0.05). We conclude that acute bouts of exercise can produce
      cardioprotective effects without an elevation of HSP 72.

PMID- 10070098
TI  - Nicotine-modified postinfarction left ventricular remodeling.
AB  - Cigarette smoking has been noted to impair wound healing in tissues such as skin,
      bone, and gut. This study was designed to examine whether nicotine adversely
      affects postinfarction cardiac wound healing and remodeling in an experimental
      model of myocardial infarction. For this purpose, two groups of rats were
      studied. The control group received a simple bandage, and the nicotine group had
      a section (1.75 mg/day) of a nicotine patch attached on their backs. After a 7
      day treatment period, an anterior wall infarction was induced. A bandage-free 7
      day healing period followed, after which hearts were isolated for mechanical
      tests. Nicotine-treated rats developed significantly enlarged left ventricles
      with thin, infarcted walls and a rightward shift in the passive pressure-volume
      relationship. Pressure-strain analysis also indicated possible changes in the
      material properties of the wound for nicotine-treated rats. In conclusion,
      nicotine has significant adverse effects on postinfarction healing and left
      ventricular remodeling. These observations have important clinical implications
      because of the enhanced risk for development of heart failure.

PMID- 10070099
TI  - Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively
      applied to the endothelium.
AB  - In rat mesenteric artery, endothelium-derived hyperpolarizing factor (EDHF) is
      blocked by a combination of apamin and charybdotoxin (ChTX). The site of action
      of these toxins has not been established. We compared the effects of ChTX and
      apamin applied selectively to the endothelium and to the smooth muscle. In
      isometrically mounted arteries, ACh (0.01-10 micrometers), in the presence of
      indomethacin (2.8 microM) and Nomega-nitro-L-arginine methyl ester (L-NAME) (100
      microM), concentration dependently relaxed phenylephrine (PE)-stimulated tone
      (EC50 50 nM; n = 10). Apamin (50 nM) and ChTX (50 nM) abolished this relaxation
      (n = 5). In pressurized arteries, ACh (10 microM), applied intraluminally in the
      presence of indomethacin (2.8 microM) and L-NAME (100 microM), dilated both PE
      stimulated (0.3-0.5 microM; n = 5) and myogenic tone (n = 3). Apamin (50 nM ) and
      ChTX (50 nM) applied intraluminally abolished ACh-induced dilatations. Bath
      superperfusion of apamin and ChTX did not affect ACh-induced dilatations of
      either PE-stimulated (n = 5) or myogenic tone (n = 3). This is the first
      demonstration that ChTX and apamin act selectively on the endothelium to block
      EDHF-mediated relaxation.

PMID- 10070100
TI  - Adenosine receptor subtypes in the heart: therapeutic opportunities and
      challenges.

PMID- 10070101
TI  - Effects and interactions of opioids on plasma exudation induced by cigarette
      smoke in guinea pig bronchi.
AB  - The effects of opioids on cigarette smoke-induced plasma exudation were
      investigated in vivo in the main bronchi of anesthetized guinea pigs, with Evans
      blue dye as a plasma marker. Acute inhalation of cigarette smoke increased plasma
      exudation by 216% above air control values. Morphine, 0.1-10 mg/kg but not 30
      mg/kg, inhibited the exudation but had no significant effect on substance P
      induced exudation. Both 10 and 30 mg/kg of morphine increased exudation in air
      control animals, an effect inhibited by antihistamines but not by a tachykinin
      neurokinin type 1-receptor antagonist. Naloxone inhibited all morphine responses.
      Cigarette smoke-induced plasma exudation was inhibited by a mu-opioid-receptor
      agonist (DAMGO) but not by agonists at delta (DPDPE)- or kappa (U-50488H)
      receptors. None of these agonists affected exudation in air control animals.
      DPDPE prevented the inhibition by DAMGO of cigarette smoke-induced plasma
      exudation, and the combination of DAMGO and DPDPE increased exudation in air
      control animals. Prevention of inhibition and the combination-induced increase
      were inhibited by antihistamines or the mast cell-stabilizing drug sodium
      cromoglycate. U-50488H did not alter the response to either DAMGO or DPDPE. We
      conclude that, in guinea pig main bronchi in vivo, mu-opioid-receptor agonists
      inhibit cigarette smoke-induced plasma exudation via a prejunctional mechanism.
      Plasma exudation induced by mu- and delta-receptor interactions is due to
      endogenous histamine release from mast cells.

PMID- 10070102
TI  - Inhibition of hSP-B promoter in respiratory epithelial cells by a dominant
      negative retinoic acid receptor.
AB  - Retinoic acid (RA) receptors (RARs) belong to the nuclear hormone receptor
      superfamily and play important roles in lung differentiation, growth, and gene
      regulation. Surfactant protein (SP) B is a small hydrophobic protein synthesized
      and secreted by respiratory epithelial cells in the lung. Expression of the SP-B
      gene is modulated at the transcriptional and posttranscriptional levels. In the
      present work, immunohistochemical staining revealed that RAR-alpha is present on
      day 14.5 of gestation in the fetal mouse lung. To assess whether RAR is required
      for SP-B gene transcription, a dominant negative mutant human (h) RAR-alpha403
      was generated. The hRAR-alpha403 mutant was transcribed and translated into the
      truncated protein product by reticulocyte lysate in vitro. The mutant retained
      DNA binding activity in the presence of retinoid X receptor-gamma to an RA
      response element in the hSP-B promoter. When transiently transfected into
      pulmonary adenocarcinoma epithelial cells (H441 cells), the mutant hRAR-alpha403
      was readily detected in the cell nucleus. Cotransfection of the mutant hRAR
      alpha403 repressed activity of the hSP-B promoter and inhibited RA-induced
      surfactant proprotein B production in H441 cells, supporting the concept that RAR
      is required for hSP-B gene transcription in vitro.

PMID- 10070103
TI  - TNF-alpha upregulates Gialpha and Gqalpha protein expression and function in
      human airway smooth muscle cells.
AB  - Chronic inflammation is a characteristic feature of asthma. Multiple inflammatory
      mediators are released within the asthmatic lung, some of which may have
      detrimental effects on signal transduction pathways in airway smooth muscle. The
      effects of tumor necrosis factor (TNF)-alpha on the expression and function of
      muscarinic receptors and guanine nucleotide-binding protein (G protein) alpha
      subunits were examined in human airway smooth muscle cells. Cultured human airway
      smooth muscle cells were incubated in serum-free culture medium for 72 h in the
      presence and absence of 10 ng/ml of TNF-alpha, after which the cells were lysed
      and subjected to electrophoresis and Galphai-2, Gqalpha, and Gsalpha protein
      subunits were detected by immunoblot analysis with specific antisera. TNF-alpha
      treatment for 72 h significantly increased the expression of Galphai-2 and
      Gqalpha proteins and enhanced carbachol (10(-7) M)-mediated inhibition of
      adenylyl cyclase activity and inositol phosphate synthesis. These data provide
      new evidence demonstrating that TNF-alpha not only increases expression of
      Galphai-2 and Gqalpha proteins but also augments the associated signal
      transduction pathways that would facilitate increased tone of airway smooth
      muscle.

PMID- 10070104
TI  - Modulation of human airway smooth muscle proliferation by type 3
      phosphodiesterase inhibition.
AB  - Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human
      airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective
      phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase
      inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) on proliferation of cultured HASM cells. At concentrations selective for
      the type 3 phosphodiesterase isoform, siguazodan inhibited both [3H]thymidine
      incorporation (IC50 2 microM) and the increase in cell number (10 microM; 64%
      reduction) induced by platelet-derived growth factor-BB (20 ng/ml). These effects
      were mimicked by IBMX. At concentrations selective for type 4 phosphodiesterase
      inhibition, rolipram was without effect. A 20-min exposure to siguazodan and
      rolipram did not increase whole cell cAMP levels. However, in HASM cells
      transfected with a cAMP-responsive luciferase reporter (p6CRE/Luc), increases in
      cAMP-driven luciferase expression were seen with siguazodan (3.9-fold) and IBMX
      (16.5-fold). These data suggest that inhibition of the type 3 phosphodiesterase
      isoform present in airway smooth muscle results in inhibition of mitogenic
      signaling, possibly through an increase in cAMP-driven gene expression.

PMID- 10070105
TI  - Facilitatory beta2-adrenoceptors on cholinergic and adrenergic nerve endings of
      the guinea pig trachea.
AB  - Using electrical field stimulation of epithelium-denuded intact guinea pig
      tracheal tube preparations, we studied the presence and role of prejunctional
      beta2-adrenoceptors by measuring evoked endogenous acetylcholine (ACh) and
      norepinephrine (NE) release directly. Analysis of ACh and NE was through two HPLC
      systems with electrochemical detection. Electrical field stimulation (150 mA, 0.8
      ms, 16 Hz, 5 min, biphasic pulses) released 29.1 +/- 2.5 pmol ACh/g tissue and
      70.2 +/- 6.2 pmol NE/g tissue. Preincubation for 15 min with the selective beta2
      adrenoceptor agonist fenoterol (1 microM) increased both ACh and NE overflow to
      178 +/- 28 (P < 0.01) and 165 +/- 12% (P < 0.01), respectively, of control
      values, increases that were abolished completely by the selective beta2
      adrenoceptor antagonist ICI-118551 (1 microM). Further experiments with
      increasing fenoterol concentrations (0.1-100 microM) and different preincubation
      periods (1, 5, and 15 min) showed a strong and concentration-dependent
      facilitation of NE release, with maximum response levels decreasing (from nearly
      5-fold to only 2.5-fold of control value) with increasing agonist contact time.
      In contrast, sensitivity of facilitatory beta2-adrenoceptors on cholinergic
      nerves to fenoterol gradually increased when the incubation period was prolonged;
      in addition, a bell-shaped concentration-response relationship was found at 15
      min of preincubation. Fenoterol concentration-response relationships (15-min
      agonist preincubation) in the presence of atropine and yohimbine (1 microM each)
      were similar in the case of NE release, but in the case of ACh release, the bell
      shape was lost. The results indicate a differential capacity and response time
      profile of facilitatory prejunctional beta2-adrenoceptors on adrenergic and
      cholinergic nerve terminals in the guinea pig trachea and suggest that the
      receptors on adrenergic nerves are more susceptible to desensitization.

PMID- 10070106
TI  - Critical role of glass fiber length in TNF-alpha production and transcription
      factor activation in macrophages.
AB  - Recent studies have demonstrated that dielectrophoresis is an efficient method
      for the separation of fibers according to fiber length. This method allows the
      investigation of fiber-cell interactions with fiber samples of the same
      composition but of different lengths. In the present study, we analyzed the
      effects of length on the interaction between glass fibers and macrophages by
      focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)
      alpha in a mouse macrophage cell line (RAW 264.7). The underlying molecular
      mechanisms controlling TNF-alpha production were investigated at the gene
      transcription level. The results show that glass fibers induced TNF-alpha
      production in macrophages and that this induction was associated with activation
      of the gene promoter. Activation of the transcription factor nuclear factor (NF)
      kappaB was responsible for this induced promoter activity. The inhibition of both
      TNF-alpha production and NF-kappaB activation by N-acetyl-L-cysteine, an
      antioxidant, indicates that generation of oxidants may contribute to the
      induction of this cytokine and activation of this transcription factor by glass
      fibers. Long fibers (17 micrometer) were significantly more potent than short
      fibers (7 micrometer) in inducing NF-kappaB activation, the gene promoter
      activity, and the production of TNF-alpha. This fiber length-dependent difference
      in the stimulatory potency correlated with the fact that macrophages were able to
      completely engulf short glass fibers, whereas phagocytosis of long glass fibers
      was incomplete. These results suggest that fiber length plays a critical role in
      the potential pathogenicity of glass fibers.

PMID- 10070107
TI  - S-nitrosoglutathione enhances neutrophil DNA fragmentation and cell death.
AB  - Enhancing the clearance of neutrophils by enhancing apoptotic cell death and
      macrophage recognition may be beneficial in acute lung injury. Exogenous nitric
      oxide gas depresses neutrophil oxidative functions and accelerates cell death (A.
      H. Daher, J. D. Fortenberry, M. L. Owens, and L. A. Brown. Am. J. Respir. Cell
      Mol. Biol. 16: 407-412, 1997). We hypothesized that S-nitrosoglutathione (GSNO),
      a physiologically relevant nitric oxide donor, could also enhance neutrophil DNA
      fragmentation. Neutrophils were incubated for 2-24 h in the absence and presence
      of GSNO (dose range 0.1-5 mM) and evaluated for cell death by a fluorescent
      viability/cytotoxicity assay. Neutrophil DNA fragmentation was assessed by cell
      death detection ELISA and by terminal deoxynucleotidyltransferase-mediated
      fluorescence-labeled dUTP nick end labeling assay. Neutrophil oxidative function
      was also determined. Incubation with GSNO increased cell death at 2, 4, and 24 h.
      GSNO incubation for 24 h significantly increased DNA fragmentation in a dose
      dependent fashion at 0.5 (median 126% of control value; P = 0.002) and 5 mM (185%
      of control value; P = 0.002) by terminal deoxynucleotidyltransferase-mediated
      fluorescence-labeled dUTP nick end labeling and at 0.5 mM by ELISA (164% of
      control value; P = 0.03). The apoptosis-to-total cell death ratio increased with
      increasing GSNO concentration (P < 0.05). Effects were mitigated by coincubation
      with superoxide dismutase. Five millimolar GSNO decreased overall superoxide
      generation and O2 consumption but not when adjusted for dead neutrophils. GSNO
      significantly enhances cell death and neutrophil DNA fragmentation in a dose
      dependent fashion.

PMID- 10070108
TI  - Protective effects of transient HO-1 overexpression on susceptibility to oxygen
      toxicity in lung cells.
AB  - Rat fetal lung cells (RFL-6) were transiently transfected with a full-length rat
      heme oxygenase (HO)-1 cDNA construct and then exposed to hyperoxia (95% O2-5%
      CO2) for 48 h. Total HO activity and HO-1 protein were measured as well as cell
      viability, lactate dehydrogenase (LDH) release, protein oxidation, lipid
      peroxidation, and total glutathione to measure oxidative injury. HO-1
      overexpression resulted in increased total HO activity (2-fold), increased HO-1
      protein (1.5-fold), and increased cell proliferation. Immunohistochemistry
      revealed perinuclear HO-1 localization, followed by migration to the nucleus by
      day 3. Decreased cell death, protein oxidation, and lipid peroxidation but
      increased LDH release and glutathione depletion were seen with HO-1
      overexpression. Reactive iron content could not explain the apparent loss of cell
      membrane integrity. With the addition of tin mesoporphyrin, total HO activity was
      decreased and all changes in injury parameters were normalized to control values.
      We conclude that moderate overexpression of HO-1 is protective against oxidative
      injury, but we speculate that there is a beneficial threshold of HO-1 expression.

PMID- 10070109
TI  - Localization of a candidate surfactant convertase to type II cells, macrophages,
      and surfactant subfractions.
AB  - Pulmonary surfactant exists in the alveolus in several distinct subtypes that
      differ in their morphology, composition, and surface activity. Experiments by
      others have implicated a serine hydrolase in the production of the inactive small
      vesicular subtype of surfactant (N. J. Gross and R. M. Schultz. Biochim. Biophys.
      Acta 1044: 222-230, 1990). Our laboratory recently identified this enzyme in the
      rat as the serine carboxylesterase ES-2 [F. Barr, H. Clark, and S. Hawgood. Am.
      J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L404-L410, 1998]. In the present
      study, we determined the cellular sites of expression of ES-2 in rat lung using a
      digoxygenin-labeled ES-2 riboprobe. ES-2 mRNA was localized to type II cells and
      alveolar macrophages but not to Clara cells. Using a specific ES-2 antibody, we
      determined the protein distribution of ES-2 in the lung by immunohistochemistry,
      and it was found to be consistent with the sites of mRNA expression. Most of the
      ES-2 in rat bronchoalveolar lavage is in the surfactant-depleted supernatant, but
      ES-2 was also consistently localized to the small vesicular surfactant
      subfraction presumed to form as a consequence of conversion activity. These
      results are consistent with a role for endogenous lung ES-2 in surfactant
      metabolism.

PMID- 10070110
TI  - Changes in surfactant-associated protein mRNA profile in growth-restricted fetal
      sheep.
AB  - To test the hypothesis that chronic placental insufficiency resulting in fetal
      growth restriction causes an increase in fetal lung surfactant-associated protein
      (SP) gene expression, we embolized chronically catheterized fetal sheep (n = 6)
      daily using nonradioactive microspheres in the abdominal aorta for 21 days
      (between 0.74 and 0.88 of gestation) until fetal arterial oxygen content was
      reduced by approximately 40-50%. Control animals (n = 7) received saline only.
      Basal fetal plasma cortisol concentration was monitored. At the end of the
      experiment, fetal lung tissues were collected, and ratios of tissue levels of SP
      A, SP-B, and SP-C mRNA to 18S rRNA were determined by standard Northern blot
      analysis. Total DNA content of fetal lungs was reduced by 30% in the embolized
      group compared with control group (P = 0.01). There was a 2.7-fold increase in
      fetal lung SP-A mRNA (P < 0.05) and a 3.2-fold increase in SP-B mRNA (P < 0.01)
      in the chronically embolized group compared with those in the control group. SP-A
      and SP-B mRNA tissue levels were highly correlated with the mean fetal plasma
      cortisol levels on days 20-21 (r = 0.90, P < 0.01 for SP-A mRNA and r = 0.94, P <
      0.01 for SP-B mRNA). SP-C mRNA tissue levels were not significantly affected by
      placental insufficiency. We conclude that fetal growth restriction due to
      placental insufficiency is associated with alterations in fetal lung SP,
      suggesting enhanced lung maturation that was highly dependent on the degree of
      increase in fetal plasma cortisol levels.

PMID- 10070111
TI  - Nitric oxide-mediated regulation of transepithelial sodium and chloride transport
      in murine nasal epithelium.
AB  - Transepithelial ion transport is regulated by a variety of cellular factors. In
      light of recent evidence that nitric oxide (NO) production is decreased in cystic
      fibrosis airways, we examined the role of NO in regulating sodium and chloride
      transport in murine nasal epithelium. Acute intervention with the inducible NO
      synthase (iNOS)-selective inhibitor S-methylisothiourea resulted in an increase
      of amiloride-sensitive sodium absorption observed as a hyperpolarization of nasal
      transepithelial potential difference. Inhibition of iNOS expression with
      dexamethasone also hyperpolarized transepithelial potential difference, but only
      a portion of this increase proved to be amiloride sensitive. Chloride secretion
      was significantly inhibited in C57BL/6J mice by the addition of both S
      methylisothiourea and dexamethasone. Mice lacking iNOS expression [NOS2(-/-)]
      also had a decreased chloride-secretory response compared with control mice.
      These data suggest that constitutive NO production likely plays some role in the
      downregulation of sodium absorption and leads to an increase in transepithelial
      chloride secretion.

PMID- 10070112
TI  - beta2-adrenoceptor agonists reduce the decline of rat diaphragm twitch force
      during severe hypoxia.
AB  - The aim of the present study was to investigate the in vitro effects of the short
      acting beta2-adrenoceptor agonist salbutamol and the long-acting beta2
      adrenoceptor agonist salmeterol on hypoxia-induced rat diaphragm force reduction.
      In vitro diaphragm twitch force (Pt) and maximal tetanic force (Po) of isolated
      diaphragm muscle strips were measured for 90 min during hyperoxia (tissue bath
      PO2 83.8 +/- 0.9 kPa and PCO2 3.9 +/- 0.1 kPa) or severe hypoxia (PO2 7.1 +/- 0.3
      kPa and PCO2 3.9 +/- 0.1 kPa) in the presence and absence of 1 microM salbutamol
      or 1 microM salmeterol. During hyperoxia, salbutamol and salmeterol did not
      significantly alter the time-related decreases in Pt and Po (to approximately 50%
      of initial values). Salbutamol had no effects on Po or the Pt-to-Po ratio.
      Salmeterol treatment significantly reduced Po and increased the Pt-to-Po ratio
      during hyperoxia (P < 0.05 compared with control value). Hypoxia resulted in a
      severe decrease in Pt (to approximately 30% of initial value) and Po after 90
      min. Both salbutamol and salmeterol significantly reduced the decline in Pt
      during hypoxia (P < 0.05). The reduction in Po was not prevented. Salbutamol
      increased Pt rapidly but transiently. Salmeterol had a delayed onset of effect
      and a longer duration of action. Addition of 1 microM propranolol (a nonselective
      beta-adrenoceptor antagonist) did not alter Pt, Po, or the Pt-to-Po ratio during
      hypoxia but completely blocked the inotropic effects of salbutamol and
      salmeterol, indicating that these effects are dependent on beta2-adrenoceptor
      agonist-related processes.

PMID- 10070113
TI  - TNF-alpha increases ceramide without inducing apoptosis in alveolar type II
      epithelial cells.
AB  - Ceramide is a bioactive lipid mediator that has been observed to induce apoptosis
      in vitro. The purpose of this study was to determine whether endogenous ceramide,
      generated in response to in vivo administration of tumor necrosis factor-alpha
      (TNF-alpha), increases apoptosis in primary rat alveolar type II epithelial
      cells. Intratracheal instillation of TNF-alpha (5 microgram) produced a decrease
      in sphingomyelin and activation of a neutral sphingomyelinase. These changes were
      associated with a significant increase in lung ceramide content. TNF-alpha
      concomitantly activated the p42/44 extracellular signal-related kinases and
      induced nuclear factor-kappaB activation in the lung. Hypodiploid nuclei studies
      revealed that intratracheal TNF-alpha did not increase type II cell apoptosis
      compared with that in control cells after isolation. A novel observation from
      separate in vitro studies demonstrated that type II cells undergo a gradual
      increase in apoptosis after time in culture, a process that was accelerated by
      exposure of cells to ultraviolet light. However, culture of cells with a cell
      permeable ceramide, TNF-alpha, or a related ligand, anti-CD95, did not increase
      apoptosis above the control level. The results suggest that ceramide resulting
      from TNF-alpha activation of sphingomyelin hydrolysis might activate the mitogen
      activated protein kinase and nuclear factor-kappaB pathways without increasing
      programmed cell death in type II cells.

PMID- 10070114
TI  - Surfactant function and composition after free radical exposure generated by
      transition metals.
AB  - Surfactant dysfunction in acute lung injury has been postulated as a result of
      free radical damage to lipid and protein components. This study examines whether
      transition metals with different redox potentials and different binding
      affinities for lipids and proteins affect interfacial properties differently.
      Purified whole calf lung surfactant (CLS) was incubated with 0.125 mM Fe2+, Fe3+,
      Fe3+-EDTA complex, or Cu2+ either alone or with 0.25 mM H2O2 or H2O2 plus 0.25 mM
      ascorbate for 4 and 24 h. Lipid peroxidation was assessed by measurement of
      thiobarbituric acid-reactive substances (TBARS), and free radical-mediated
      alterations in protein structure were assessed by fluorescamine assay and Western
      blot analysis. Function was assayed by pulsating bubble surfactometry. Lipid
      peroxidation was detected in samples incubated with Fe2+, Fe3+, and Fe3+-EDTA but
      not with Cu2+. All transition metal-based free radical systems affected
      surfactant protein composition by fluorescamine assay, indicating free radical
      mediated modification of protein side chains. Western blot analysis demonstrated
      surfactant protein A modification, with the generation of higher- and lower
      molecular-mass immunoreactive products. Despite biochemical evidence of lipid and
      protein modification, surfactant dysfunction was minimal and was manifest as an
      increase in the compression ratio required to achieve surface tension < 1 dyn/cm.
      This dysfunction was readily reversed by the addition of 5 mM Ca2+ either before
      or after oxidation. These data indicate that copper- and iron-based free radical
      generating systems modify the lipid and protein components of surfactant
      differently but suggest that these changes have little effect on surfactant
      function.

PMID- 10070115
TI  - Expression of heat shock protein 72 by alveolar macrophages in hypersensitivity
      pneumonitis.
AB  - The current study was done to look at a possible role of heat shock proteins
      (HSPs) in hypersensitivity pneumonitis (HP). The specific aims were to determine
      whether there was a difference in the expression of HSP72 in alveolar macrophages
      (AMs) between mice challenged with HP antigen and saline-treated control mice and
      between AMs obtained by bronchoalveolar lavage from 18 patients with HP and 11
      normal subjects. The expression of HSP72 was studied under basal conditions and
      under a mild heat shock. HSP72 expression by AMs in response to in vitro
      stimulation with Saccharopolyspora rectivirgula was lower in AMs of control mice
      than in those of HP animals. HSP72 was constitutively expressed in AMs of both
      normal and HP subjects. Densitometric ratios showed that AMs from normal subjects
      responded to heat shock with a 39 degrees C-to-37 degrees C ratio of 1.72 +/-
      0.18 (mean +/- SE), and AMs from HP patients responded with a ratio of 1.16 +/-
      0.16 (P = 0.0377). This decreased induction by additional stress of AMs could
      lead to an altered immunoregulatory activity and account for the inflammation
      seen in HP.

PMID- 10070116
TI  - Protein kinase C isoforms in human airway smooth muscle cells: activation of PKC
      zeta during proliferation.
AB  - Protein kinase C (PKC) is implicated in the regulation of smooth muscle
      contractility and growth. We have previously described the pattern of isoform
      expression of PKC in canine airway smooth muscle. This study identified the
      isoforms present in human cultured airway smooth muscle cells and also addressed
      the question of whether mitogenesis in these cells is associated with changes in
      a specific isoform, PKC-zeta. Western blot analysis revealed the presence of PKC
      alpha, -betaI, and -betaII of the conventional group; PKC-delta, -theta, 
      epsilon, and -eta of the novel group; and PKC-zeta, -mu, and -iota of the
      atypical group. There was a significant increase in density of the Western blot
      for PKC-zeta in cells proliferating in response to 10% fetal bovine serum (FBS)
      to 372 +/- 115% of control values (P < 0.05; n = 3 patients) in the cytosolic
      fraction. Platelet-derived growth factor (PDGF) produced increases in PKC-zeta in
      both the cytosolic and membrane fractions to 210 +/- 49 and 443 +/- 227%,
      respectively, of control values (P < 0.05; n = 4 patients). There was no change
      in expression of PKC-alpha, -betaI, -betaII, -theta, -epsilon, -eta, -delta, or 
      iota in response to the same stimuli. PGE2 (1 microM) added to the cells 30 min
      before PDGF reduced incorporation of [3H]thymidine from 5,580 +/- 633 (SE) to 3,
      980 +/- 126 dpm (P < 0.05; n = 3 patients) and, in addition, reduced expression
      of PKC-zeta in the membrane fraction as determined by Western blotting from 266
      +/- 66 to 110 +/- 4% of control values (P < 0.05; n = 3 patients). PKC-zeta
      activity in stimulated cells (10% FBS), as assessed by immunoprecipitation and
      phosphorylation of glycogen synthase peptide, was approximately 3-fold greater
      than that in unstimulated cells, and the amount of PKC-zeta protein correlated
      with isoenzyme activity (r2 = 0.91; P < 0.02; n = 4 patients). In conclusion,
      this study 1) provides the first description of which isoforms of PKC are present
      in human cultured airway smooth muscle cells and 2) shows that proliferation of
      these cells is associated with upregulation of PKC-zeta. Whether activation of
      PKC-zeta is a primary or secondary event in airway smooth muscle cell
      proliferation remains to be determined.

PMID- 10070117
TI  - Inducible NO synthase inhibition attenuates shear stress-induced pulmonary
      vasodilation in the ovine fetus.
AB  - Recent studies have suggested that type II (inducible) nitric oxide (NO) synthase
      (NOS II) is present in the fetal lung, but its physiological roles are uncertain.
      Whether NOS II activity contributes to the NO-mediated fall in pulmonary vascular
      resistance (PVR) during shear stress-induced pulmonary vasodilation is unknown.
      We studied the hemodynamic effects of two selective NOS II antagonists
      [aminoguanidine (AG) and S-ethylisothiourea (EIT)], a nonselective NOS antagonist
      [nitro-L-arginine (L-NNA)], and a nonselective vasoconstrictor (U-46619) on PVR
      during partial compression of the ductus arteriosus (DA) in 20 chronically
      prepared fetal lambs (mean age 132 +/- 2 days, term 147 days). At surgery,
      catheters were placed in the left pulmonary artery (LPA) for selective drug
      infusion, an ultrasonic flow transducer was placed on the LPA to measure blood
      flow, and an inflatable vascular occluder was placed loosely around the DA for
      compression. On alternate days, a brief intrapulmonary infusion of normal saline
      (control), AG, EIT, L-NNA, or U-46619 was infused in random order into the LPA.
      The DA was compressed to increase mean pulmonary arterial pressure (MPAP) 12-15
      mmHg above baseline values and held constant for 30 min. In control studies, DA
      compression reduced PVR by 42% from baseline values (P < 0.01). L-NNA treatment
      completely blocked the fall in PVR during DA compression. AG and EIT attenuated
      the decrease in PVR by 30 and 19%, respectively (P < 0.05). Nonspecific elevation
      in PVR by U-46619 did not affect the fall in PVR during DA compression.
      Immunostaining for NOS II identified this isoform in airway epithelium and
      vascular smooth muscle in the late-gestation ovine fetal lung. We conclude that
      selective NOS II antagonists attenuate but do not block shear stress-induced
      vasodilation in the fetal lung. We speculate that stimulation of NOS II activity,
      perhaps from smooth muscle cells, contributes in part to the NO-mediated fall in
      PVR during shear stress-induced pulmonary vasodilation.

PMID- 10070118
TI  - Mediators of anaphylaxis but not activated neutrophils augment cholinergic
      responses of equine small airways.
AB  - Neutrophilic inflammation in small airways (SA) and bronchospasm mediated via
      muscarinic receptors are features of chronic obstructive pulmonary disease in
      horses (COPD). Histamine, serotonin, and leukotrienes (LTs) are reported to be
      involved in the exacerbation of COPD, and currently, histamine has been shown to
      increase tension response to electrical field simulation (EFS) in equine SA. We
      tested the effects of these mediators and the effects of activated neutrophils on
      the cholinergic responses in SA. Histamine, serotonin, and LTD4 had a synergistic
      effect on EFS responses and only an additive effect on the tension response to
      exogenous ACh or methacholine. Atropine and TTX entirely eliminated the EFS
      induced tension response in the presence of all three inflammatory mediators,
      indicating that augmentation of the EFS response applies only to the endogenous
      cholinergic response. Neutrophils isolated from control and COPD-affected horses
      were activated by zymosan, producing 18.1 +/- 2.3 and 25.0 +/- 2.3 nmol
      superoxide. 10(6) cells-1. 30 min-1, respectively. However, in contrast to the
      profound effect of mediators, incubation of SA for over 1 h in a suspension of up
      to 30 x 10(6) zymosan-treated neutrophils/ml did not significantly affect EFS
      responses of SA isolated from either control or COPD-affected horses. We conclude
      that in equine SA 1) the endogenous cholinergic responses are subject to strong
      facilitation by inflammatory mediators; 2) activated neutrophils do not affect
      cholinergic responses in SA; and 3) in acute bouts of equine COPD, histamine,
      LTD4, and serotonin (mediators primarily associated with type I allergic
      reaction) rather than mediators derived from neutrophils most likely contribute
      to increased cholinergic airway tone.

PMID- 10070119
TI  - Induction of thioredoxin and thioredoxin reductase gene expression in lungs of
      newborn primates by oxygen.
AB  - Thioredoxin (TRX) is a potent protein disulfide oxidoreductase important in
      antioxidant defense and regulation of cell growth and signal transduction
      processes, among them the production of nitric oxide. We report that lung TRX and
      its reductase, TR, are specifically upregulated at birth by O2. Throughout the
      third trimester, mRNAs for TRX and TR were expressed constitutively at low levels
      in fetal baboon lungs. However, after premature birth (125 or 140 of 185 days
      gestation), lung TRX and TR mRNAs increased rapidly with the onset of O2 or air
      breathing. Lung TRX mRNA also increased in lungs of term newborns with air
      breathing. Premature animals (140 days) breathing 100% O2 develop chronic lung
      disease within 7-14 days. These animals had greater TRX and TR mRNAs after 1, 6,
      or 10 days of life than fetal control animals. In 140-day animals given lesser O2
      concentrations (as needed) who do not develop chronic lung disease, lung TRX and
      TR mRNAs were also increased on days 1 and 6 but not significantly on day 10. In
      fetal distal lung explant culture, mRNAs for TRX and TR were elevated within 4 h
      in 95% O2 relative to 1% O2, and the response was similar at various gestations.
      In contrast, TRX protein did not increase in lung explants from premature animals
      (125 or 140 days) but did in those from near-term (175-day) fetal baboons after
      exposure to hyperoxia. However, lung TRX protein and activity, as well as TR
      activity, eventually did increase in vivo in response to hyperoxia (6 days).
      Increases in TRX and TR mRNAs in response to 95% O2 also were observed in adult
      baboon lung explants. When TRX redox status was determined, increased O2 tension
      shifted TRX to its oxidized form. Treatment of lung explants with actinomycin D
      inhibited TRX and TR mRNA increases in 95% O2, indicating transcriptional
      regulation by O2. The acute increase in gene expression for both TRX and TR in
      response to O2 suggests an important role for these proteins during the
      transition from relatively anaerobic fetal life to O2 breathing at birth.

PMID- 10070120
TI  - Surfactant protein A enhances the binding and deacylation of E. coli LPS by
      alveolar macrophages.
AB  - Surfactant protein (SP) A and SP-D are involved in multiple immunomodulatory
      functions of innate host defense partly via their interaction with alveolar
      macrophages (AMs). In addition, both SP-A and SP-D bind to bacterial
      lipopolysaccharide (LPS). To investigate the functional significance of this
      interaction, we first tested the ability of SP-A and SP-D to enhance the binding
      of tritium-labeled Escherichia coli LPS to AMs. In contrast to SP-D, SP-A
      enhanced the binding of LPS by AMs in a time-, temperature-, and concentration
      dependent manner. Coincubation with surfactant-like lipids did not affect the SP
      A-mediated enhancement of LPS binding. At SP-A-to-LPS molar ratios of 1:2-1:3,
      the LPS binding by AMs reached 270% of control values. Second, we investigated
      the role of SP-A in regulating the degradation of LPS by AMs. In the presence of
      SP-A, deacylation of LPS by AMs increased by approximately 2.3-fold. Pretreatment
      of AMs with phosphatidylinositol-specific phospholipase C had no effect on the SP
      A-enhanced LPS binding but did reduce the amount of serum-enhanced LPS binding by
      50%, suggesting that a cell surface molecule distinct from CD14 mediates the
      effect of SP-A. Together the results for the first time provide direct evidence
      that SP-A enhances LPS binding and degradation by AMs.

PMID- 10070121
TI  - Maintenance of adenosine A1 receptor function during long-term anoxia in the
      turtle brain.
AB  - It has been established that adenosine has a critical role in the extraordinary
      ability of the turtle brain to survive anoxia. To further investigate this
      phenomenon we compared rat and turtle brain adenosine A1 receptors using
      cyclopentyl-1,3-dipropylxanthine, 8-[dipropyl-2,3-3H(N)] ([3H]DPCPX) saturation
      binding analyses and determined the effects of prolonged anoxia (6, 12, and 24 h)
      on the adenosine A1 receptor of the turtle brain. The rat brain had a 10-fold
      greater density of A1 receptors compared with the turtle [rat cortex receptor
      density (Bmax) = 1,400 +/- 134.6 fmol/mg protein, turtle forebrain Bmax = 103.2
      +/- 4.60 fmol/mg protein] and a higher affinity [dissociation constant (Kd) rat
      cortex = 0.328 +/- 0.035 nM, Kd turtle forebrain = 1.16 +/- 0.06 nM]. However,
      the turtle Kd is within the reported mammalian range, and the Bmax is similar to
      that reported for other poikilotherms. Unlike the mammal, in which A1 receptor
      function is rapidly compromised in anoxia, in the turtle forebrain no significant
      changes in the A1 receptor population were seen during 24-h anoxia. However, in
      the hindbrain, whereas the Bmax remained unchanged, the Kd significantly
      decreased from 2.1 to 0.5 nM after 6 h anoxia and this higher affinity was
      maintained at 12- and 24-h anoxia. These findings indicate that, unlike the GABAA
      receptor, the protective effectiveness of adenosine in the anoxic turtle brain is
      not related to an enhanced receptor number. Protection from a hypoxia-induced
      compromise in A1 receptor function and an increased A1 sensitivity in the
      hindbrain may be important factors for maintaining the adenosine-mediated
      downregulation of energy demand during long-term anoxia.

PMID- 10070122
TI  - Fatty acid binding protein in heart and skeletal muscles of the migratory
      barnacle goose throughout development.
AB  - The long-distance migratory flights of birds are predominantly fueled by the
      oxidation of fatty acids, which are sourced primarily from extracellular adipose
      stores. These fatty acids have to be transported, via the circulatory system, to
      the mitochondria of the active muscles. An important facilitator of fatty acid
      transport within the cytoplasm of muscle cells is fatty acid binding protein
      (FABP), which serves as an intracellular carrier of long-chain fatty acids. In
      mammals, the muscular FABP content is related to the fatty acid oxidation
      capacity of the tissue. The aim of this study was to measure FABP in samples
      taken from the cardiac, pectoralis, and semimembranosus muscles of a long
      distance avian migrant, the barnacle goose (Branta leucopsis), at various stages
      of development. Western blot analysis identified a single goose muscle protein of
      15 kDa that was able to bind fatty acids and showed a 66% cross-reactivity with
      antibodies against human heart-type FABP. Captive goslings showed no significant
      changes in FABP content of either the heart (62.6 +/- 10.6 microgram/g wet wt) or
      the semimembranosus muscle (8.4 +/- 1.9 microgram/g wet wt) during development.
      However, in both peripheral and deep sites within the pectoralis muscle, FABP
      content of samples taken from captive goslings were approximately 10-fold higher
      throughout development and reached values of 30-40 microgram/g wet wt in fledging
      goslings at 7 wk of age. A further twofold higher value was seen in wild but not
      in captive goslings immediately before migration (12 wk of age). Similarly, FABP
      content was significantly higher in pectoralis samples taken from wild adults
      (94.3 +/- 3.6 microgram/g wet wt) compared with those from captive adults (60.5
      +/- 3.6 micro/g wet wt). These results suggest that the experience of flight
      activity may be of critical importance in achieving maximal expression of FABP in
      the pectoralis muscles of postfledging and mature geese immediately before
      migration.

PMID- 10070123
TI  - Acute-phase responses in transgenic mice with CNS overexpression of IL-1 receptor
      antagonist.
AB  - The interleukin-1 (IL-1) receptor antagonist (IL-1ra) is an endogenous antagonist
      that blocks the effects of the proinflammatory cytokines IL-1alpha and IL-1beta
      by occupying the type I IL-1 receptor. Here we describe transgenic mice with
      astrocyte-directed overexpression of the human secreted IL-1ra (hsIL-1ra) under
      the control of the murine glial fibrillary acidic protein (GFAP) promoter. Two
      GFAP-hsIL-1ra strains have been generated and characterized further: GILRA2 and
      GILRA4. These strains show a brain-specific expression of the hsIL-1ra at the
      mRNA and protein levels. The hsIL-1ra protein was approximated to approximately
      50 ng/brain in cytosolic fractions of whole brain homogenates, with no
      differences between male and female mice or between the two strains. Furthermore,
      the protein is secreted, inasmuch as the concentration of hsIL-1ra in the
      cerebrospinal fluid was 13 (GILRA2) to 28 (GILRA4) times higher in the transgenic
      mice than in the control animals. To characterize the transgenic phenotype, GILRA
      mice and nontransgenic controls were injected with recombinant human IL-1beta
      (central injection) or lipopolysaccharide (LPS, peripheral injection). The
      febrile response elicited by IL-1beta (50 ng/mouse icv) was abolished in hsIL-1ra
      overexpressing animals, suggesting that the central IL-1 receptors were occupied
      by antagonist. The peripheral LPS injection (25 micrograms/kg ip) triggered a
      fever in overexpressing and control animals. Moreover, no differences were found
      in LPS-induced (100 and 1,000 micrograms/kg ip; 1 and 6 h after injection) IL
      1beta and IL-6 serum levels between GILRA and wild-type mice. On the basis of
      these results, we suggest that binding of central IL-1 to central IL-1 receptors
      is not important in LPS-induced fever or LPS-induced IL-1beta and IL-6 plasma
      levels.

PMID- 10070124
TI  - Central administration of rat IL-6 induces HPA activation and fever but not
      sickness behavior in rats.
AB  - Interleukin (IL)-6 has been proposed to mediate several sickness responses,
      including brain-mediated neuroendocrine, temperature, and behavioral changes.
      However, the exact mechanisms and sites of action of IL-6 are still poorly
      understood. In the present study, we describe the effects of central
      administration of species-homologous recombinant rat IL-6 (rrIL-6) on the
      induction of hypothalamic-pituitary-adrenal (HPA) activity, fever, social
      investigatory behavior, and immobility. After intracerebroventricular
      administration of rrIL-6 (50 or 100 ng/rat), rats demonstrated HPA and febrile
      responses. In contrast, rrIL-6 alone did not induce changes in social
      investigatory and locomotor behavior at doses of up to 400 ng/rat.
      Coadministration of rrIL-6 (100 ng/rat) and rrIL-1beta (40 ng/rat), which alone
      did not affect the behavioral responses, reduced social investigatory behavior
      and increased the duration of immobility. Compared with rhIL-6,
      intracerebroventricular administration of rrIL-6 (100 ng/rat) induced higher HPA
      responses and early-phase febrile responses. This is consistent with a higher
      potency of rrIL-6, compared with rhIL-6, in the murine B9 bioassay. We conclude
      that species-homologous rrIL-6 alone can act in the brain to induce HPA and
      febrile responses, whereas it only reduces social investigatory behavior and
      locomotor activity in the presence of IL-1beta.

PMID- 10070125
TI  - Effect of prostanoids and their precursors on the aggregation of rainbow trout
      thrombocytes.
AB  - The role of prostanoids and their precursor fatty acids in the aggregatory
      response of thrombocytes (platelet equivalents of fish) from the rainbow trout,
      Oncorhynchus mykiss, was studied. Aggregation of these cells was induced by the
      thromboxane mimetic U-46619 or arachidonic acid (AA) in the presence of human or
      trout fibrinogen. The production of TXB2/3 by thrombocytes in response to
      stimulation with AA was inhibited by aspirin, ibuprofen, and indomethacin.
      However, thrombocyte aggregation in response to AA stimulation was not
      significantly altered by these agents at the concentrations tested (10-100
      microM), with the exception of indomethacin at 20 and 40 microM. Effects on
      cytosolic calcium concentration have been suggested as an alternative mechanism
      for the inhibitory action of indomethacin on human platelet aggregation. The
      present study, however, failed to identify this as a mechanism for the inhibition
      of U-46619-induced trout thrombocyte aggregation by indomethacin. The
      polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid both
      exhibited an inhibitory effect on U-46619-induced thrombocyte aggregation similar
      to that observed with mammalian platelets. Unlike the case in mammalian
      hemostasis, prostacyclin inhibited thrombocyte aggregation only at high
      concentrations (>5 microM). Prostaglandin E2, however, inhibited thrombocyte
      aggregation at much lower concentrations (>0.01 microM), suggesting that it may
      be the major inhibitory eicosanoid in trout.

PMID- 10070126
TI  - Insulin resistance of muscle glucose transport in male and female rats fed a high
      sucrose diet.
AB  - It has been reported that, unlike high-fat diets, high-sucrose diets cause
      insulin resistance in the absence of an increase in visceral fat and that the
      insulin resistance develops only in male rats. This study was done to 1)
      determine if isolated muscles of rats fed a high-sucrose diet are resistant to
      stimulation of glucose transport when studied in vitro and 2) obtain information
      regarding how the effects of high-sucrose and high-fat diets on muscle insulin
      resistance differ. We found that, compared with rat chow, semipurified high
      sucrose and high-starch diets both caused increased visceral fat accumulation and
      insulin resistance of skeletal muscle glucose transport. Insulin responsiveness
      of 2-deoxyglucose (2-DG) transport measured in epitrochlearis and soleus muscles
      in vitro was decreased approximately 40% (P < 0.01) in both male and female rats
      fed a high-sucrose compared with a chow diet. The high-sucrose diet also caused
      resistance of muscle glucose transport to stimulation by contractions. There was
      a highly significant negative correlation between stimulated muscle 2-DG
      transport and visceral fat mass. In view of these results, the differences in
      insulin action in vivo observed by others in rats fed isocaloric high-sucrose and
      high-starch diets must be due to additional, specific effects of sucrose that do
      not carry over in muscles studied in vitro. We conclude that, compared with rat
      chow, semipurified high-sucrose and high-cornstarch diets, like high-fat diets,
      cause increased visceral fat accumulation and severe resistance of skeletal
      muscle glucose transport to stimulation by insulin and contractions.

PMID- 10070127
TI  - Effect of individual or combined ablation of the nuclear groups of the lamina
      terminalis on water drinking in sheep.
AB  - The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT),
      and median preoptic nucleus (MnPO) were ablated either individually or in various
      combinations, and the effects on drinking induced by either intravenous infusion
      of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were
      studied. Ablation of either the OVLT or SFO alone did not affect drinking in
      response to intravenous 4 M NaCl, although combined ablation of these two
      circumventricular organs substantially reduced but did not abolish such drinking.
      Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did
      not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total
      destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO)
      abolished acute osmotically induced drinking. The large lesions also reduced
      drinking after water deprivation, whereas none of the other lesions significantly
      affected such drinking. None of these lesions altered feeding. The results show
      that all parts of the lamina terminalis play a role in the drinking induced by
      acute increases in plasma tonicity. The lamina terminalis appears to play a less
      crucial role in the drinking response after water deprivation than for the
      drinking response to acute intravenous infusion of hypertonic saline.

PMID- 10070128
TI  - Cardiovascular, endocrine, and renal effects of urodilatin in normal humans.
AB  - Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on
      separate study days were studied in eight normal subjects with use of a
      randomized, double-blind protocol. All doses decreased renal plasma flow
      (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7-22%) and
      urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min
      1, respectively). Glomerular filtration rate did not increase significantly with
      any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke
      volume (10 and 20%) without changing mean arterial blood pressure and heart rate.
      The two highest doses elicited larger decreases in stroke volume (17 and 21%) but
      also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%),
      such that cardiac output remained unchanged. Hematocrit and plasma protein
      concentration increased with the three highest doses. The renin-angiotensin
      aldosterone system was inhibited by the three lowest doses but activated by the
      hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors
      of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide
      immunoreactivity (including urodilatin) and plasma cGMP increased dose
      dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37
      +/- 17 micrograms/min). Use of a newly developed assay revealed that baseline
      urinary urodilatin excretion rate was low (<10 pg/min) and that fractional
      excretion of urodilatin remained below 0.1%. The results indicate that even
      moderately natriuretic doses of urodilatin exert protracted effects on systemic
      hemodynamic, endocrine, and renal functions, including decreases in cardiac
      output and renal blood flow, without changes in arterial pressure or glomerular
      filtration rate, and that filtered urodilatin is almost completely removed by the
      renal tubules.

PMID- 10070129
TI  - Electrophysiological properties of rat lateral parabrachial neurons in vitro.
AB  - Anatomical studies have demonstrated that the lateral parabrachial nucleus (LPBN)
      is composed of at least seven separate subnuclei distinguished by cell
      morphology, spatial clustering, and afferent and efferent connectivity. We
      hypothesized that neurons within the subnuclear clusters of the LPBN might have
      distinct electrophysiological properties that correlate with cellular morphology.
      An in vitro slice preparation was used to intracellularly record the intrinsic
      properties of 64 neurons located within the external lateral (EL) and central
      lateral (CL) subnuclei of the LPBN in adult rats. Analysis of intrinsic
      properties revealed that neurons in the EL subnucleus had significantly wider
      action potentials and on the average demonstrated more spike frequency adaptation
      during 2 s of depolarization compared with CL neurons. The majority of both EL
      and CL area neurons expressed delayed excitation (DE) after membrane
      hyperpolarization. DE was eliminated with the A-current blocker 4-aminopyridine
      (1.5-5 mM). Postinhibitory rebound was also observed in a subpopulation of EL and
      CL neurons. Morphological analysis of 11 LPBN neurons, which were
      electrophysiologically characterized and filled with 2% biocytin, failed to
      demonstrate an association between morphology and the electrophysiological
      profiles of LPBN neurons. The lack of distinct "type" of neuron within a single
      subnucleus of the LPBN is in agreement with recent findings reported from the
      neonatal rat.

PMID- 10070130
TI  - Muscarinic blockade inhibits gastric emptying of mixed-nutrient meal: effects of
      weight and gender.
AB  - We compared the vagal contribution to gastric emptying in lean and obese subjects
      by monitoring gastric emptying of a meal during muscarinic blockade. Lean (n = 6)
      and obese subjects (n = 6) underwent two treatments: 1) saline infusion and 2)
      atropine infusion [0.4 mg/m2 bolus, 0.4 mg. (m2)-1. h-1] for 2 h, initiated 30
      min before ingestion of a 600-kcal breakfast (64% carbohydrate, 23% fat, 13%
      protein) composed of orange juice (labeled with Indium-111), egg sandwich
      (labeled with Technetium-99m), cereal, milk, and banana. Anterior and posterior
      images were taken every 90 s for 90 min using a dual-headed camera. Atropine
      significantly delayed emptying of both solid (P < 0.007) and liquid (P < 0.002).
      Obese subjects exhibited a greater delay in liquid emptying during muscarinic
      blockade compared with lean subjects (P < 0.02). Female subjects exhibited a
      slower rate of gastric emptying and were less sensitive to atropine. These data
      suggest that obese subjects exhibit altered gastric cholinergic activity compared
      with lean subjects and that gender differences in gastric emptying rate may be
      due to differences in autonomic tone.

PMID- 10070131
TI  - Characterization of enteric functional changes evoked by in vivo anti-CD3 T cell
      activation.
AB  - Specific in vivo T cell activation initiated by treatment with anti-CD3
      antibodies leads to diarrhea and structural damage of the intestinal mucosa. In
      this study, the effect of T cell-induced mucosal damage on jejunal epithelial ion
      transport, muscle contractility, and neuronal ACh release was assessed in Ussing
      chambers, organ baths, and a specialized perfusion apparatus, respectively. Time
      matched control mice received hamster serum containing irrelevant antibodies.
      Jejunal segments from anti-CD3-treated mice displayed a significantly elevated
      epithelial baseline short-circuit current (which indicates increased ion
      transport) and a concomitant reduction in responsiveness to prosecretory stimuli
      (nerve stimulation, carbachol, and forskolin). Longitudinal smooth muscle
      displayed altered spontaneous contractile activity, length-tension relationships,
      and carbachol-stimulated contraction in tissues excised from mice 20 and 40 h
      posttreatment. Anti-CD3 treatment did not affect stimulated ACh release from
      myenteric plexus neurons. We conclude that specific T cell activation via anti
      CD3 antibody results in dramatic alterations in jejunal epithelial and smooth
      muscle function. Such T cell-induced changes in intestinal function may
      contribute to the symptomatology of T cell-mediated enteropathies, including
      graft-versus-host disease, celiac disease, and idiopathic inflammatory bowel
      disease.

PMID- 10070132
TI  - Norepinephrine stimulates lymphoid cell mobilization from the perfused rat spleen
      via beta-adrenergic receptors.
AB  - The possibility that norepinephrine (NE) influences lymphoid cell outflow
      independently of its vasoconstrictor action was investigated in the perfused rat
      spleen. Using agents that affect the vasoconstrictor tonus of the spleen, we
      observed an inverse correlation between flow resistance and splenic cell output.
      The curve obtained served as a reference for evaluating effects of different
      treatments on the number of cells that are mobilized at defined levels of flow
      resistance. Perfusion of the beta-adrenergic blocker propranolol either alone or
      in combination with NE lowered splenic leukocyte outflow clearly beyond the
      number of cells expected at the corresponding flow resistance. No comparable
      effects were observed when the alpha-adrenergic blocker phentolamine was
      perfused. When the vasoconstrictor effect of NE was counteracted by papaverine,
      splenic cell outflow was significantly higher than expected for the level of flow
      resistance attained. Furthermore, when NE was perfused together with endotoxin,
      which does not inhibit the vasoconstriction induced by catecholamines, splenic
      cell mobilization was severalfold higher than expected at increased flow
      resistance. Propranolol abrogated this effect to a large extent. Furthermore,
      perfusion of the beta-agonist isoproterenol stimulated lymphoid cell outflow from
      the spleen despite increased flow resistance. These studies show a dual effect of
      NE on cell mobilization from the spleen: cell retention by decreasing blood flow
      and stimulation of cell output by a beta-adrenergically mediated, smooth muscle
      independent mechanism.

PMID- 10070133
TI  - Perfusion of the human finger during cold-induced vasodilatation.
AB  - We have investigated the effect of severe local cooling on the vasomotor activity
      of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third
      finger was subjected to local cooling (3 degrees C) for 30-45 min in 21 healthy,
      thermoneutral subjects. Blood velocity in the third finger arteries of both hands
      was simultaneously recorded using ultrasound Doppler, and skin temperature and
      laser-Doppler flux from the pulp of the cooled finger were also recorded. The
      results demonstrate that the initial cold-induced vasoconstriction during severe
      local cooling involves constriction of the AVAs as well as the two main arteries
      supplying this finger. During cold-induced vasodilatation (CIVD), the maximum
      velocity values were not significantly different from those before cooling.
      Furthermore, the velocity fluctuations in the cooled finger were in most subjects
      found to be synchronous with the velocity fluctuations in the control finger.
      This indicates that the large blood flow to the finger and the high skin
      temperature during CIVD are caused by relaxation of the smooth muscle cells of
      the AVAs.

PMID- 10070134
TI  - Responses of sympathetic outflow to skin during caloric stimulation in humans.
AB  - We previously showed that caloric vestibular stimulation elicits increases in
      sympathetic outflow to muscle (MSNA) in humans. The present study was conducted
      to determine the effect of this stimulation on sympathetic outflow to skin
      (SSNA). The SSNA in the tibial and peroneal nerves and nystagmus was recorded in
      nine subjects when the external meatus was irrigated with 50 ml of cold (10
      degrees C) or warm (44 degrees C) water. During nystagmus, the SSNA in tibial and
      peroneal nerves decreased to 50 +/- 4% (with baseline value set as 100%) and 61
      +/- 4%, respectively. The degree of SSNA suppression in both nerves was
      proportional to the maximum slow-phase velocity of nystagmus. After nystagmus,
      the SSNA increased to 166 +/- 7 and 168 +/- 6%, respectively, and the degree of
      motion sickness symptoms was correlated with this SSNA increase. These results
      suggest that the SSNA response differs from the MSNA response during caloric
      vestibular stimulation and that the SSNA response elicited in the initial period
      of caloric vestibular stimulation is different from that observed during the
      period of motion sickness symptoms.

PMID- 10070135
TI  - Neurogenic origin of articular hyperemia in early degenerative joint disease.
AB  - It has been speculated that joint instability resulting from anterior cruciate
      ligament (ACL) rupture could be exacerbated by changes in vasomotor activity in
      the remaining supporting structures. In this study, the effect of ACL transection
      on medial collateral ligament (MCL) basal perfusion and its responsiveness to
      calcitonin gene-related peptide (CGRP) and sympathetic adrenergic influences was
      examined. Using urethan-anesthetized rabbits, we tested the effects of CGRP and
      its antagonist CGRP-(8-37) by topical application of these agents to the exposed
      knee while sympathetic influences were tested by electrically stimulating the
      saphenous nerve. It was found that MCL basal perfusion was elevated in ACL
      sectioned joints; however, this effect was abrogated by prior resection of the
      articular nerve supply. At the doses tested, the normal vasodilator response to
      CGRP was abolished in ACL-sectioned joints, whereas the response to CGRP-(8-37)
      was attenuated. Even under the influence of increased constrictor tone, MCL and
      capsule blood vessels still showed substantially reduced responses to exogenous
      CGRP administration. By contrast, nerve-mediated constrictor responses were
      mostly unaffected by joint instability. This study suggests that posttraumatic
      knee joint hyperemia is neurogenically mediated, possibly by increased secretion
      of CGRP.

PMID- 10070136
TI  - Ontogeny of intestinal safety factors: lactase capacities and lactose loads.
AB  - We measured intestinal safety factors (ratio of a physiological capacity to the
      load on it) for lactose digestion in developing rat pups. Specifically, we
      assessed the quantitative relationships between lactose load and the series
      capacities of lactase and the Na+-glucose cotransporter (SGLT-1). Both capacities
      increased significantly with age in suckling pups as a result of increasing
      intestinal mass and maintenance of mass-specific activities. The youngest pups
      examined (5 days) had surprisingly high safety factors of 8-13 for both lactase
      and SGLT-1, possibly because milk contains lactase substrates other than lactose;
      it also, however, suggests that their intestinal capacities were being prepared
      to meet future demands rather than just current ones. By day 10 (and also at day
      15), increased lactose loads resulted in lower safety factors of 4-6, values more
      typical of adult intestines. The safety factor of SGLT-1 in day 30 (weanling) and
      day 100 (adult) rats was only approximately 1.0. This was initially unexpected,
      because most adult intestines maintain a modest reserve capacity beyond nutrient
      load values, but postweaning rats appear to use hindgut fermentation, assessed by
      gut morphology and hydrogen production assays, as a built-in reserve capacity.
      The series capacities of lactase and SGLT-1 varied in concert with each other
      over ontogeny and as lactose load was manipulated by experimental variation in
      litter size.

PMID- 10070137
TI  - Endothelin-1 and CYP450 arachidonate metabolites interact to promote tissue
      injury in DOCA-salt hypertension.
AB  - Inhibition of cytochrome P-450 (CYP450) enzymes with cobalt chloride (CoCl2)
      prevented hypertension, organ hypertrophy, and renal injury induced by DOCA and
      salt (1% NaCl) in uninephrectomized (UNx) rats. Systolic blood pressure (SBP)
      rose to 193 +/- 6 mmHg by day 21 from control levels of 150 +/- 7 mmHg in
      response to DOCA-salt treatment, a rise that was prevented by CoCl2 (24 mg. kg-1.
      24 h-1). The effects of DOCA-salt treatment, which increased protein excretion to
      88.3 +/- 6.9 mg/24 h on day 21 from 9.0 +/- 1.1 mg/24 h on day 3, were prevented
      by CoCl2. CoCl2 also attenuated the renal and left ventricular hypertrophy and
      the increase in media-to-lumen ratio in hypertensive rats. DOCA-salt treatment
      increased excretion of endothelin (ET)-1 from 81 +/- 17 to 277 +/- 104 pg. 100 g
      body wt-1. 24 h-1 associated with a fourfold increase in 20
      hydroxyeicosatetraenoic acid (20-HETE) excretion from 3.0 +/- 1.1 to 12.2 +/- 1.9
      ng. 100 g body wt-1. 24 h-1 (days 3 vs. 21). CoCl2 blunted these increases by 58
      and 72%, respectively. In aortic rings pulsed with [3H]thymidine, ET-1 increased
      its incorporation. Dibromododec-11-enoic acid, an inhibitor of 20-HETE synthesis,
      attenuated ET-1-induced increases in [3H]thymidine incorporation. We
      distinguished effects of CoCl2 acting via CO generation vs. suppression of CYP450
      arachidonic acid metabolism by treating UNx-salt-DOCA rats with 1
      aminobenzotriazole (ABT), which suppresses CYP450 enzyme activity, and compared
      these results to those produced by CoCl2. ABT reduced hypertension, as did CoCl2.
      Unlike CoCl2, ABT did not prevent organ hypertrophy and proteinuria, suggesting
      that these effects were partially related to CO formation. Blockade of the ETA
      receptor with BMS-182874 reduced SBP, organ hypertrophy, and proteinuria,
      indicating the importance of ET-initiated abnormalities to the progression of
      lesions in UNx-salt-DOCA.

PMID- 10070138
TI  - Hypoglycemia and torpor in Siberian hamsters.
AB  - We tested whether reduced blood glucose concentrations are necessary and
      sufficient for initiation of torpor in Siberian hamsters. During spontaneous
      torpor bouts, body temperature (Tb) decreases from the euthermic value of 37 to
      <31 degrees C. Among hamsters that displayed torpor during maintenance in a short
      day length (10 h light/day) at an air temperature of 15 degrees C, blood glucose
      concentrations decreased significantly by 28% as Tb fell from 37 to <31 degrees C
      and increased during rewarming so that by the time Tb first was >36 degrees C,
      glucose concentrations had returned to the value preceding torpor. Hamsters did
      not display torpor when maintained in a long-day length (16 h light/day) and
      injected with a range of insulin doses (1-50 U/kg body mass), some of which
      resulted in sustained, pronounced hypoglycemia. We conclude that changes in blood
      glucose concentrations may be a consequence rather than a cause of the torpid
      state and question whether induction of torpor by 2-deoxy-D-glucose is due to its
      general glucoprivic actions.

PMID- 10070139
TI  - Simultaneous identification of static and dynamic vagosympathetic interactions in
      regulating heart rate.
AB  - We earlier reported that stimulation of either one of the sympathetic and vagal
      nerves augments the dynamic heart rate (HR) response to concurrent stimulation of
      its counterpart. We explained this phenomenon by assuming a sigmoidal static
      relationship between nerve activity and HR. To confirm this assumption, we
      stimulated the sympathetic and/or vagal nerve in anesthetized rabbits using large
      amplitude Gaussian white noise and determined the static and dynamic
      characteristics of HR regulation by a neural network analysis. The static
      characteristics approximated a sigmoidal relationship between the linearly
      predicted and the measured HRs (response range: 212.4 +/- 46.3 beats/min, minimum
      HR: 96.0 +/- 28.4 beats/min, midpoint of operation: 196.7 +/- 31.3 beats/min,
      maximum slope: 1.65 +/- 0.51). The maximum step responses determined from the
      dynamic characteristics were 7.9 +/- 2.9 and -14.0 +/- 4.9 beats. min-1. Hz-1 for
      the sympathetic and the vagal system, respectively. Because of these
      characteristics, changes in sympathetic or vagal tone alone can alter the dynamic
      HR response to stimulation of the other nerve.

PMID- 10070140
TI  - Role of renal medullary adenosine in the control of blood flow and sodium
      excretion.
AB  - This study determined the levels of adenosine in the renal medullary interstitium
      using microdialysis and fluorescence HPLC techniques and examined the role of
      endogenous adenosine in the control of medullary blood flow and sodium excretion
      by infusing the specific adenosine receptor antagonists or agonists into the
      renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary
      blood flows were measured using laser-Doppler flowmetry. Analysis of
      microdialyzed samples showed that the adenosine concentration in the renal
      medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly
      higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary
      interstitial infusion of a selective A1 antagonist, 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX; 300 pmol. kg-1. min-1, n = 8), did not alter renal blood
      flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast,
      renal medullary infusion of the selective A2 receptor blocker 3, 7-dimethyl-1
      propargylxanthine (DMPX; 150 pmol. kg-1. min-1, n = 9) decreased outer medullary
      blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium
      excretion by 35%. Renal medullary interstitial infusion of adenosine produced a
      dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses
      from 3 to 300 pmol. kg-1. min-1 (n = 7). These effects of adenosine were markedly
      attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a
      selective A3 receptor agonist, N6-benzyl-5'-(N-ethylcarbonxamido)adenosine (300
      pmol. kg-1. min-1, n = 6) into the renal medulla had no effect on medullary blood
      flows or renal function. Glomerular filtration rate and arterial pressure were
      not changed by medullary infusion of any drugs. Our results indicate that
      endogenous medullary adenosine at physiological concentrations serves to dilate
      medullary vessels via A2 receptors, resulting in a natriuretic response that
      overrides the tubular A1 receptor-mediated antinatriuretic effects.

PMID- 10070141
TI  - Impact of development and chronic hypoxia on NE release from adrenergic nerves in
      sheep arteries.
AB  - To examine effects of development and chronic high-altitude hypoxia on
      sympathetic nerve function in sheep, norepinephrine release was measured in vitro
      from middle cerebral and facial arteries. Capsaicin was used to test the role of
      capsaicin-sensitive sensory nerves; norepinephrine release was not altered by
      capsaicin treatment. Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor
      of NO synthase, decreased stimulation-evoked norepinephrine release in middle
      cerebral arteries from normoxic sheep with no effect in hypoxic arteries or
      facial arteries. Thus NO-releasing nerves augmented norepinephrine release.
      Furthermore, the function of NO-releasing nerves declined after chronic hypoxia.
      Despite loss of the augmenting effects of NO, stimulation-evoked fractional
      norepinephrine release was unchanged after chronic hypoxia, suggesting that
      middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked
      norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a
      decline in stimulation-evoked norepinephrine release, but there was an increase
      in the adult facial artery. In the adult, adaptation to chronic hypoxia is
      similar in both cerebral and facial arteries. However, differential adaptation in
      fetal adrenergic nerves may reflect differences in fetal redistribution of blood
      flow in the face of chronic hypoxia but could also possibly contribute to
      increased incidence of fetal morbidity.

PMID- 10070142
TI  - Time-dependent and tissue-specific effects of circulating glucose on fetal ovine
      glucose transporters.
AB  - To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we
      examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin
      responsive (GLUT-4) glucose transporter proteins by quantitative Western blot
      analysis in fetal ovine insulin-insensitive (brain and liver) and insulin
      sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose
      infusions causing fetal hyperglycemia resulted in a transient 30% increase in
      brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and
      myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational
      age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia
      caused a decline in brain GLUT-3, an increase in brain GLUT-1, and a subsequent
      decline in liver GLUT-1, with no significant change in insulin-sensitive
      myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations,
      compared with gestational age-matched sham controls. We conclude that fetal
      glucose transporters are subject to a time-dependent and tissue- and isoform
      specific differential regulation in response to altered circulating glucose
      and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3)
      are geared toward protecting the conceptus from perturbations in substrate
      availability, and the adaptations in GLUT-4 are geared toward development of
      fetal insulin resistance.

PMID- 10070143
TI  - Contribution of extracranial lymphatics and arachnoid villi to the clearance of a
      CSF tracer in the rat.
AB  - The objective of this study was to determine the relative roles of arachnoid
      villi and cervical lymphatics in the clearance of a cerebrospinal fluid (CSF)
      tracer in rats. 125I-labeled human serum albumin (125I-HSA; 100 micrograms) was
      injected into one lateral ventricle, and an Evans blue dye-rat protein complex
      was injected intravenously. Arterial blood was sampled for 3 h. Immediately after
      this, multiple cervical vessels were ligated in the same animals, and plasma
      recoveries were monitored for a further 3 h after the intracerebroventricular
      injection of 100 micrograms 131I-HSA. Tracer recovery in plasma at 3 h averaged
      (%injected dose) 0.697 +/- 0.042 before lymphatic ligation and dropped
      significantly to 0.357 +/- 0. 060 after ligation. Estimates of the rate constant
      associated with the transport of the CSF tracer to plasma were also significantly
      lower after obstruction of cervical lymphatics (from 0.584 +/- 0. 072/h to 0.217
      +/- 0.056/h). No significant changes were observed in sham-operated animals.
      Assuming that the movement of the CSF tracer to plasma in lymph-ligated animals
      was a result of arachnoid villi clearance, we conclude that arachnoid villi and
      extracranial lymphatic pathways contributed equally to the clearance of the CSF
      tracer from the cranial vault.

PMID- 10070144
TI  - Alterations in endogenous circadian rhythm of core temperature in senescent
      Fischer 344 rats.
AB  - We assessed whether alterations in endogenous circadian rhythm of core
      temperature (CRT) in aging rats are associated with chronological time or with a
      biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT
      was measured in male Fischer 344 (F344) rats beginning at age 689 days and then
      continuously until death. Young rats were also monitored. The rats were housed
      under constant dim red light at 24-26 degrees C, and core temperature was
      recorded every 10 min via biotelemetry. The CRT amplitude of the body weight
      stable (presenescent) old rats was significantly less than that of young rats at
      all analysis periods. At the onset of spontaneous rapid weight loss (senescence),
      all measures of endogenous CRT differed significantly from those in the
      presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the
      senescent rats maintained its light responsiveness as determined by an increase
      in c-fos expression after a brief light exposure. These data demonstrate that
      some characteristics of the CRT are altered slowly with chronological aging,
      whereas others occur rapidly with the onset of senescence.

PMID- 10070145
TI  - Hemodynamic and renal effects of U-46619, a TXA2/PGH2 analog, in late-pregnant
      rats.
AB  - The vasoconstrictor effects of pressor agents are attenuated during pregnancy.
      Thromboxane A2 (TXA2) is produced in great quantities during hypertension in
      pregnancy, and therefore it is important to know whether pregnancy modifies the
      pressor effects of TXA2. The TXA2 analog U-46619 was infused in anesthetized,
      acutely prepared and conscious, chronically prepared late-pregnant and
      nonpregnant female rats to examine its systemic hemodynamic and renal effects.
      Mean arterial pressure (MAP) and total peripheral resistance (TPR) were lower in
      anesthetized pregnant than nonpregnant rats (P < 0.01). The infusion of U-46619
      into the aortic arch resulted in elevation of MAP only in pregnant rats, due to a
      greater elevation of TPR (60 +/- 17%) compared with nonpregnant rats (36 +/- 6%,
      P < 0.05). The pressor effect of intravenously infused U-46619 was also enhanced
      in conscious pregnant versus nonpregnant rats, and the increase in renal vascular
      resistance was undiminished. U-46619 increased hematocrit and plasma protein
      concentration more during pregnancy, which suggested greater reduction of plasma
      volume. The urinary excretion of sodium (-1.49 +/- 0.25 vs. -0.54 +/- 0.24
      micromol/min) and water was reduced more in pregnant than nonpregnant rats during
      U-46619 (P < 0.01). Thus the MAP and renal effects of the TXA2 analog are
      exaggerated during pregnancy in the rat.

PMID- 10070146
TI  - A unique Na+/H+ exchanger, analogous to NHE1, in the chicken embryonic
      fibroblast.
AB  - We report the characterization of an Na+/H+ exchanger (NHE) in embryonic
      fibroblasts (SL-29 cells) of the chicken, a terrestrial vertebrate, where Na+
      conservation is important. This exchanger is electroneutral, has a single Na+
      binding site, and is highly sensitive to amiloride (IC50 2 microM), dimethyl
      amiloride (350 nM), and ethyl-isopropyl amiloride (25 nM). It is stimulated by
      serum, transforming growth factor-alpha, hypertonicity, and okadaic acid.
      Although these features make it resemble mammalian NHE1, other characteristics
      suggest distinct differences. First, in contrast to mammalian NHE1 it is
      inhibited by cAMP and shows a biphasic response to phorbol esters and a highly
      variable response to increased intracellular Ca2+ concentration. Second, whereas
      full-length human and rat NHE1 cDNA probes recognize a 4.8-kb transcript in rat
      tissues, they recognize only a 3.9-kb transcript in chicken tissues. An antibody
      against amino acids 631-746 of human NHE1 sequence fails to recognize a protein
      in SL-29 cells. Rat NHE2 and NHE3 probes do not recognize any transcript in
      chicken fibroblasts. The SL-29 exchanger differs markedly from the previously
      characterized chicken intestinal apical exchanger in its amiloride sensitivity
      and regulation by phorbol esters. These results suggest that a modified version
      of mammalian NHE1 is present in chicken tissues and imply that another
      functionally distinct Na+/H+ exchanger is expressed in aves.

PMID- 10070147
TI  - Second messenger production in avian medullary nephron segments in response to
      peptide hormones.
AB  - We examined the sites of peptide hormone activation within medullary nephron
      segments of the house sparrow (Passer domesticus) kidney by measuring rates of
      hormone-induced generation of cyclic nucleotide second messenger. Thin descending
      limbs, thick ascending limbs, and collecting ducts had baseline activity of
      adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31,
      and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity
      increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase
      in the thin descending limb was stimulated approximately twofold by parathyroid
      hormone (PTH) but not by any of the other hormones tested [arginine vasotocin
      (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(
      6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH;
      however, glucagon and isoproterenol had no effect, and ANP stimulated neither
      cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was
      stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not
      stimulate cGMP accumulation in this segment. These data support a tubular action
      of AVT and PTH in the avian renal medulla.

PMID- 10070148
TI  - Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded
      rat.
AB  - The present study examined whether an abnormality in the myogenic response of
      renal arterioles that impairs autoregulation of renal blood flow (RBF) and
      glomerular capillary pressure (PGC) contributes to the development of renal
      damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney,
      cortical, and medullary blood flow and PGC were compared in young (12 wk old) FHH
      and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume
      expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGC
      were significantly greater in FHH than in FHL rats. Autoregulation of renal and
      cortical blood flow was significantly impaired in FHH rats compared with results
      obtained in FHL rats. Myogenically mediated autoregulation of PGC was
      significantly greater in FHL than in FHH rats. PGC rose from 46 +/- 1 to 71 +/- 2
      mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg
      in FHH rats, whereas it only increased from 39 +/- 2 to 53 +/- 1 mmHg in FHL
      rats. Isolated perfused renal interlobular arteries from FHL rats constricted by
      10% in response to elevations in transmural pressure from 70 to 120 mmHg. In
      contrast, the diameter of vessels from FHH rats increased by 15%. These results
      indicate that the myogenic response of small renal arteries is altered in FHH
      rats, and this contributes to an impaired autoregulation of renal blood flow and
      elevations in PGC in this strain.

PMID- 10070149
TI  - Role of central melanocortins in endotoxin-induced anorexia.
AB  - Inflammation and microbial infection produce symptoms, including fever, anorexia,
      and hypoactivity, that are thought to be mediated by endogenous proinflammatory
      cytokines. Melanocortins are known to act centrally to suppress effects on fever
      and other sequelae of proinflammatory cytokine actions in the central nervous
      system, but the roles of melanocortins in anorexia and hypoactivity occurring
      during the acute phase response are unknown. The present study was designed to
      determine the effects of exogenous and endogenous alpha-melanocyte stimulating
      hormone (alpha-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to
      their effects on fever. Rats were fasted overnight to promote feeding behavior,
      then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min
      later by intracerebroventricular injection of either alpha-MSH or the
      melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food
      intake, locomotor activity, and body temperature (Tb) were monitored during the
      ensuing 24-h period. Each of two intracerebroventricular doses of alpha-MSH (30
      and 300 ng) potentiated the suppressive effects of LPS on food intake and
      locomotion, despite the fact that the higher dose alleviated LPS-induced fever.
      In control rats that were not treated with LPS, only the higher dose of alpha-MSH
      significantly inhibited food intake, and Tb and locomotor activity were
      unaffected. To assess the roles of endogenous central melanocortins, LPS-treated
      rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R
      blockade did not affect Tb or food intake in the absence of LPS treatment, but it
      reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced
      fever without altering the LPS-induced suppression of locomotion. Taken together,
      the results suggest that exogenous and endogenous melanocortins acting centrally
      exert divergent influences on different aspects of the acute phase response,
      suppressing LPS-induced fever but contributing to LPS-induced anorexia and
      hypoactivity.

PMID- 10070150
TI  - Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously
      hypertensive rats.
AB  - The aim of the present study was to determine the receptor subtype involved in
      arginine vasopressin (AVP)-induced modulation of baroreflex function in
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel
      nonpeptide AVP V1- and V2-receptor antagonists. Baroreceptor heart rate (HR)
      reflex was investigated in both SHR and WKY rats which were intravenously
      administered the selective V1- and V2-receptor antagonists OPC-21268 and OPC
      31260, respectively. Baroreflex function was assessed by obtaining alternate
      pressor and depressor responses to phenylephrine and sodium nitroprusside,
      respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex
      activity was tested before and after intravenous administration of vehicle (20%
      DMSO), OPC-21268 (10 mg/kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not
      significantly alter basal mean arterial pressure (MAP) and HR values or
      baroreflex function in SHR or WKY rats. The V1-receptor antagonist had no
      significant effect on resting MAP or HR values or on baroreflex parameters in
      both groups of rats, although this dose was shown to significantly inhibit the
      pressor response to AVP (5 ng iv; ANOVA, P < 0.05). In SHR but not WKY rats the
      V2-receptor antagonist significantly attenuated the gain (or slope) of the
      baroreflex curve (to 73 +/- 3 and 79 +/- 7% of control for 1 and 10 mg/kg,
      respectively), although AVP-induced pressor responses were also attenuated with
      the higher dose of the V2-receptor antagonist. These findings suggest that AVP
      tonically enhances baroreflex function through a V2 receptor in the SHR.

PMID- 10070151
TI  - Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating:
      immunochemical/behavioral evidence.
AB  - Cells within the lateral hypothalamic area (LHA) are important in eating control.
      Glutamate or its analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA),
      elicit intense eating when microinjected there, and, conversely, LHA-administered
      NMDA receptor antagonists suppress deprivation- and NMDA-elicited eating. The
      subunit composition of LHA NMDA receptors (NMDA-Rs) mediating feeding, however,
      has not yet been determined. Identifying this is important, because distinct
      second messengers/modulators may be activated by NMDA-Rs with differing
      compositions. To begin to address this, we detected LHA NR2A and NR2B subunits by
      immunoblotting and NR2B subunits by immunohistochemistry using subunit-specific
      antibodies. To help determine whether NMDA-Rs mediating feeding might contain
      these subunits, we conducted behavioral studies using LHA-administered
      ifenprodil, an antagonist selective for NR2A- and/or NR2B-containing NMDA-Rs at
      the doses we used (0.001-100 nmol). Ifenprodil maximally suppressed NMDA- and
      deprivation-elicited feeding by 63 and 39%, respectively, but failed to suppress
      KA-elicited eating, suggesting its actions were behaviorally specific.
      Collectively, these results suggest that LHA NMDA-Rs, some of which contribute to
      feeding control, are composed of NR2A and/or NR2B subunits, and implicate NR2A-
      and/or NR2B-linked signal transduction in feeding behavior.

PMID- 10070152
TI  - Developmental regulation of genes mediating murine brain glucose uptake.
AB  - We examined the molecular mechanisms that mediate the developmental increase in
      murine whole brain 2-deoxyglucose uptake. Northern and Western blot analyses
      revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial)
      and GLUT-3 (neuronal) membrane-spanning facilitative glucose transporter mRNA and
      protein concentrations. Nuclear run-on experiments revealed that these
      developmental changes in GLUT-1 and -3 were regulated posttranscriptionally. In
      contrast, the mRNA and protein levels of the mitochondrially bound glucose
      phosphorylating hexokinase I enzyme were unaltered. However, hexokinase I enzyme
      activity increased in an age-dependent manner suggestive of a posttranslational
      modification that is necessary for enzymatic activation. Together, the postnatal
      increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic activity led
      to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the
      molecular mechanisms regulating the increase in the three different gene products
      may vary, the age-dependent increase of all three constituents appears essential
      for meeting the increasing demand of the maturing brain to fuel the processes of
      cellular growth, differentiation, and neurotransmission.

PMID- 10070153
TI  - Genetic control of renal thiazide receptor response to dietary NaCl and
      hypertension.
AB  - Excess NaCl increases blood pressure in some strains of animals but not others.
      An 8% NaCl diet did not change renal thiazide receptor (TZR) density in two salt
      resistant normotensive rat strains (Wistar-Kyoto and Sprague-Dawley) [Fanestil,
      D. D., D. A. Vaughn, and P. Blakely. Am. J. Physiol. 273 (Regulatory Integrative
      Comp. Physiol. 42): R1241-R1245, 1997]. However, the renal response to salt
      differs in normal and hypertensive kidneys [Rettig, R., N. Bandelow, O. Patschan,
      B. Kuttler, B. Frey, and A. Uber. J. Hum. Hypertens. 10: 641-644, 1996].
      Therefore, we examined two strains with salt-aggravated hypertension. Renal TZR
      did not change when Dahl-S (salt sensitive) animals became hypertensive with 8%
      dietary NaCl. In contrast, renal TZR decreased 34%, whereas blood pressure
      increased further, in SHR with 8% dietary NaCl. Blood pressure increased after NG
      nitro-L-arginine in SHR, but renal TZR did not change, indicating the salt
      induced decrease in TZR in SHR cannot be attributed nonspecifically to elevated
      arterial pressure. We conclude that the renal response to NaCl-induced increases
      in blood pressure can be genetically modulated independently of the genes that
      mediate either the primary hypertension or the salt sensitivity of the
      hypertension. This finding may be of use in future studies directed at
      identifying genotypes associated with salt-dependent hypertension.

PMID- 10070154
TI  - System identification of closed-loop cardiovascular control mechanisms: diabetic
      autonomic neuropathy.
AB  - We applied cardiovascular system identification (CSI) to characterize closed-loop
      cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN).
      The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively
      measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume
      (ILV) to characterize four physiological coupling mechanisms, two of which are
      autonomically mediated (the heart rate baroreflex and the coupling of
      respiration, measured in terms of ILV, to heart rate) and two of which are
      mechanically mediated (the coupling of ventricular contraction to the generation
      of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control
      and 60 diabetic subjects who were classified as having minimal, moderate, or
      severe DAN on the basis of standard autonomic tests. The autonomically mediated
      couplings progressively decreased with increasing severity of DAN, whereas the
      mechanically mediated couplings were essentially unchanged. CSI identified
      differences between the minimal DAN and control groups, which were
      indistinguishable based on the standard autonomic tests. CSI may provide a
      powerful tool for assessing DAN.

PMID- 10070155
TI  - Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal
      lamb ductus arteriosus.
AB  - Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have
      adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2
      inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To
      examine this hypothesis, we used ductus arteriosus obtained from late-gestation
      fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus
      expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis).
      Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was
      found only in the endothelial cells lining the ductus lumen (by
      immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2
      synthesis was consistent with the immunohistochemical results: in the intact
      ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent
      proportions; in the endothelium-denuded ductus, COX-2 no longer played a
      significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was
      66% as effective as the selective COX-1 inhibitor valeryl salicylate and the
      nonselective COX inhibitor indomethacin in causing contraction of the ductus in
      vitro. At this time, caution should be used when recommending COX-2 inhibitors
      for use in pregnant women.

PMID- 10070156
TI  - Long-term regulation of aquaporins in the kidney.
AB  - The discovery of the aquaporin family of water channels has greatly improved our
      understanding of how water crosses epithelial cells, particularly in the kidney.
      The study of the mechanisms involved in the regulation of collecting duct water
      permeability, in particular, has advanced very rapidly since the identification
      and characterization of aquaporin-2 (AQP2) in 1993. One of the more surprising
      findings has been the dramatic long-term changes that are seen in the abundance
      of this protein, as well as the recognition that these changes represent a way of
      modulating the acute antidiuretic effects of vasopressin. Furthermore, such
      changes seem to be of etiological and pathological significance in a number of
      clinical disorders of water balance. This review focuses on the various
      conditions in which AQP2 expression is altered (either increased or decreased)
      and on what this can tell us about the signals and mechanisms controlling these
      changes. Ultimately, this may be of great value in the clinical management of
      water balance disorders. Evidence is also now beginning to emerge that there are
      similar changes in the expression of other renal aquaporins, which had previously
      been thought to provide an essentially constitutive water permeability pathway,
      suggesting that they too should be considered as regulatory factors in the
      control of body water balance.

PMID- 10070157
TI  - Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of
      nitric oxide.
AB  - In rats with streptozotocin (STZ)-induced diabetes, the renal vasoconstrictor
      effect of adenosine is enhanced. We investigated the role of nitric oxide (NO) in
      the renal vascular response to exogenous and endogenous adenosine in control and
      STZ diabetic rats. Exogenous adenosine (0.01-100 nmol) injected into the
      abdominal aorta decreased renal blood flow (RBF) in a dose-dependent manner to a
      much greater extent in STZ rats than in control rats (P < 0.001). Inhibition of
      NO synthesis with Nomega-nitro-L-arginine (L-NNA, 30 micromol/kg iv) and with
      renal perfusion pressure controlled potentiated the adenosine-induced renal
      vasoconstriction to a significantly greater extent in control rats than in STZ
      rats. In control rats, L-NNA shifted the dose-response curve of exogenous
      adenosine-induced RBF reductions to the left by a factor of 32 [half-maximal
      effective dose (ED50), from 5.5 to 0.17 nmol adenosine, n = 6] and in STZ rats
      only by a factor of 4.6 (ED50, from 0.32 to 0.07 nmol adenosine, n = 6). The
      renal response to endogenous adenosine was assessed by the magnitude of the
      postocclusive reduction of RBF (POR) after a 30-s renal artery occlusion. POR was
      markedly enhanced in STZ rats (-67.8 +/- 3.8%, P < 0.001) compared with control
      rats (-38.8 +/- 4.3%). L-NNA markedly enhanced POR in control rats but did not
      increase POR in STZ rats. These findings demonstrate a greater potentiation of
      the adenosine-induced renal vasoconstriction in the presence of L-NNA infusion in
      control rats compared with STZ rats. We conclude that the increased
      vasoconstrictor sensitivity of the diabetic renal vasculature to adenosine is
      caused by a defective NO-dependent renal vasodilation of the afferent arteriole
      in diabetic rats.

PMID- 10070158
TI  - Isoforms of the Na-K-2Cl cotransporter in murine TAL I. Molecular
      characterization and intrarenal localization.
AB  - We have identified several alternatively spliced cDNAs encoding mBSC1, an apical
      bumetanide-sensitive Na+-K+-2Cl- cotransporter from mouse kidney. Two full-length
      clones were isolated, designated C4 and C9, predicting proteins of 770 and 1,095
      amino acids, respectively. The C4 isoforms are generated by utilization of an
      alternative polyadenylation site located within the intron between exons 16 and
      17 of the mBSC1 gene on chromosome 2; the resultant transcripts predict a
      truncated COOH terminus ending in a unique 55 amino acid sequence. The predicted
      C4 and C9 COOH termini differ in the distribution of putative phosphorylation
      sites for both protein kinase A and C. Independent splicing events involve three
      previously described cassette exons, which are predicted to encode most of the
      second transmembrane domain. A total of six different isoforms are expressed,
      generated by the combinatorial association of three cassette exons and two
      alternative 3' ends. C9-specific and C4-specific antibodies detect proteins of
      approximately 150 and 120 kDa, respectively, in mouse kidney. Immunofluorescence
      and immunohistochemistry indicate expression of both COOH-terminal isoforms
      within the thick ascending limb of the loop of Henle (TAL). However, staining
      with the C4 antibody is more heterogeneous, with a decreased proportion of
      positive cells in the cortical TAL. Functional expression in Xenopus oocytes
      indicates a dominant negative function for C4 isoforms [companion study, C.
      Plata, D. B. Mount, V. Rubio, S. C. Hebert, and G. Gamba. Am. J. Physiol. 276
      (Renal Physiol. 45): F347-F358, 1999], and the differential expression of these
      isoforms may contribute to functional heterogeneity of Na+-K+-2Cl- cotransport in
      mouse TAL.

PMID- 10070159
TI  - Isoforms of the Na-K-2Cl cotransporter in murine TAL II. Functional
      characterization and activation by cAMP.
AB  - The functional properties of alternatively spliced isoforms of the mouse apical
      Na+-K+-2Cl- cotransporter (mBSC1) were examined, using expression in Xenopus
      oocytes and measurement of 22Na+ or 86Rb+ uptake. A total of six isoforms,
      generated by the combinatorial association of three 5' exon cassettes (A, B, and
      F) with two alternative 3' ends, are expressed in mouse thick ascending limb
      (TAL) [see companion article, D. B. Mount, A. Baekgaard, A. E. Hall, C. Plata, J.
      Xu, D. R. Beier, G. Gamba, and S. C. Hebert. Am. J. Physiol. 276 (Renal Physiol.
      45): F347-F358, 1999]. The two 3' ends predict COOH-terminal cytoplasmic domains
      of 129 amino acids (the C4 COOH terminus) and 457 amino acids (the C9 terminus).
      The three C9 isoforms (mBSC1-A9/F9/B9) all express Na+-K+-2Cl- cotransport
      activity, whereas C4 isoforms are nonfunctional in Xenopus oocytes. Activation or
      inhibition of protein kinase A (PKA) does not affect the activity of the C9
      isoforms. The coinjection of mBSC1-A4 with mBSC1-F9 reduces tracer uptake,
      compared with mBSC1-F9 alone, an effect of C4 isoforms that is partially reversed
      by the addition of cAMP-IBMX to the uptake medium. The inhibitory effect of C4
      isoforms is a dose-dependent function of the alternatively spliced COOH terminus.
      Isoforms with a C4 COOH terminus thus exert a dominant negative effect on Na+-K+
      2Cl- cotransport, a property that is reversed by the activation of PKA. This
      interaction between coexpressed COOH-terminal isoforms of mBSC1 may account for
      the regulation of Na+-K+-2Cl- cotransport in the mouse TAL by hormones that
      generate cAMP.

PMID- 10070160
TI  - Developmental expression of sodium entry pathways in rat nephron.
AB  - During the past several years, sites of expression of ion transport proteins in
      tubules from adult kidneys have been described and correlated with functional
      properties. Less information is available concerning sites of expression during
      tubule morphogenesis, although such expression patterns may be crucial to renal
      development. In the current studies, patterns of renal axial differentiation were
      defined by mapping the expression of sodium transport pathways during
      nephrogenesis in the rat. Combined in situ hybridization and immunohistochemistry
      were used to localize the Na-Pi cotransporter type 2 (NaPi2), the bumetanide
      sensitive Na-K-2Cl cotransporter (NKCC2), the thiazide-sensitive Na-Cl
      cotransporter (NCC), the Na/Ca exchanger (NaCa), the epithelial sodium channel
      (rENaC), and 11beta-hydroxysteroid dehydrogenase (11HSD). The onset of expression
      of these proteins began in post-S-shape stages. NKCC2 was initially expressed at
      the macula densa region and later extended into the nascent ascending limb of the
      loop of Henle (TAL), whereas differentiation of the proximal tubular part of the
      loop of Henle showed a comparatively retarded onset when probed for NaPi2. The
      NCC was initially found at the distal end of the nascent distal convoluted tubule
      (DCT) and later extended toward the junction with the TAL. After a period of
      changing proportions, subsegmentation of the DCT into a proximal part expressing
      NCC alone and a distal part expressing NCC together with NaCa was evident. Strong
      coexpression of rENaC and 11HSD was observed in early nascent connecting tubule
      (CNT) and collecting ducts and later also in the distal portion of the DCT.
      Ontogeny of the expression of NCC, NaCa, 11HSD, and rENaC in the late distal
      convolutions indicates a heterogenous origin of the CNT. These data present a
      detailed analysis of the relations between the anatomic differentiation of the
      developing renal tubule and the expression of tubular transport proteins.

PMID- 10070161
TI  - Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat
      kidney.
AB  - BMP-7, a member of the bone morphogenic protein subfamily (BMPs) of the
      transforming growth factor-beta superfamily of secreted growth factors, is
      abundantly expressed in the fetal kidney. The precise role of this protein in
      renal physiology or pathology is unknown. A cDNA that encodes rat BMP-7 was
      cloned and used as a probe to localize BMP-7 mRNA expression by in situ
      hybridization in the adult rat kidney. The highest expression of BMP-7 mRNA could
      be seen in tubules of the outer medulla. In glomeruli, a few cells, mainly
      located at the periphery of the glomerular tuft, showed specific and strong
      signals. Also, high BMP-7 mRNA expression could be localized to the adventitia of
      renal arteries, as well as to the epithelial cell layer of the renal pelvis and
      the ureter. Preliminary evidence suggests that BMP-7 enhances recovery when
      infused into rats with ischemia-induced acute renal failure. We examined BMP-7
      mRNA expression in kidneys with acute renal failure induced by unilateral renal
      artery clamping. BMP-7 mRNA abundance as analyzed by solution hybridization was
      reduced in ischemic kidneys after 6 and 16 h of reperfusion compared with the
      contralateral kidney. In situ hybridization in ischemic kidneys showed a marked
      decrease of BMP-7 mRNA in the outer medulla and in glomeruli. Utilizing rat
      metanephric mesenchymal cells in culture, we also demonstrate that BMP-7 induces
      epithelial cell differentiation. Taken together, these data suggest that BMP-7 is
      important in both stimulating and maintaining a healthy differentiated epithelial
      cell phenotype.

PMID- 10070162
TI  - Tumor necrosis factor-alpha and ceramide induce cell death through different
      mechanisms in rat mesangial cells.
AB  - It has been proposed that ceramide acts as a cellular messenger to mediate tumor
      necrosis factor-alpha (TNF-alpha)-induced apoptosis. Based on this hypothesis, it
      was postulated that resistance of some cells to TNF-alpha cytotoxicity was due to
      an insufficient production of ceramide on stimulation by TNF-alpha. The present
      study was initiated to investigate whether this was the case in mesangial cells,
      which normally are insensitive to TNF-alpha-induced apoptosis. Our results
      indicate that although C2 ceramide was toxic to mesangial cells, the cell death
      it induced differed both morphologically and biochemically from that induced by
      TNF-alpha in the presence of cycloheximide (CHX). The most apparent effect of C2
      ceramide was to cause cells to swell, followed by disruption of the cell
      membrane. It is evident that C2 ceramide caused cell death by necrosis, whereas
      TNF-alpha in the presence of CHX killed the cells by apoptosis. C2 ceramide did
      not mimic the effects of TNF-alpha on the activation of c-Jun NH2-terminal
      protein kinase and nuclear factor-kappaB transcription factor. Although mitogen
      activated protein kinase [extracellular signal-related kinase (ERK)] was
      activated by both C2 ceramide and TNF-alpha, such activation appeared to be
      mediated by different mechanisms as judged from the kinetics of ERK activation.
      Furthermore, the cleavage of cytosolic phospholipase A2 during cell death induced
      by C2 ceramide and by TNF-alpha in the presence of CHX showed distinctive
      patterns. The present study provides evidence that apoptosis and necrosis use
      distinctive signaling machinery to cause cell death.

PMID- 10070163
TI  - A novel p64-related Cl- channel: subcellular distribution and nephron segment
      specific expression.
AB  - Several closely related proteins that have been implicated as chloride channels
      of intracellular membranes have recently been described. We report here the
      molecular cloning and characterization of a new member of this family from human
      cells. On the basis of sequence similarity, we conclude that this new protein
      represents the human version of a previously described protein from rat brain
      named p64H1. The human version of p64H1 (huH1) is a 28.7-kDa protein that shows
      an apparent molecular mass of 31 kDa by SDS-PAGE. A single 4.5-kb message is
      detected on Northern blots and is present in all tissues probed. The protein is
      expressed in an intracellular vesicular pattern in Panc-1 cells that is distinct
      from the endoplasmic reticulum, fluid-phase endocytic, and transferrin-recycling
      compartments, but which does colocalize with caveolin. In human kidney, huH1 is
      highly expressed in a diffuse pattern in the apical domain of proximal tubule
      cells. huH1 is expressed less abundantly in a vesicular pattern in glomeruli and
      distal nephron.

PMID- 10070164
TI  - Resetting of exaggerated tubuloglomerular feedback activity in acutely volume
      expanded young SHR.
AB  - One purpose of the present study was to evaluate the ability of 7-wk-old
      spontaneously hypertensive rats (SHR) to reset tubuloglomerular feedback (TGF)
      activity in response to acute volume expansion (VE). Second, we evaluated the
      contribution of ANG II, via its action on AT1 receptors, to TGF control of
      glomerular function during VE. TGF was assessed by micropuncture methods and
      proximal tubular stop-flow pressure (SFP) determinations in SHR, Wistar-Kyoto
      rats (WKY), and Sprague-Dawley rats (SD). During euvolemia SHR exhibited enhanced
      TGF activity. In the same animals acute VE was achieved by infusion of saline (5
      ml. h-1. 100 g body wt-1). VE led to resetting of TGF in all three strains.
      Maximal SFP responses, elicited by a 30-40 nl/min loop of Henle perfusion rate,
      decreased from 19 to 12 mmHg in SHR and, on average, from 11 to 5 mmHg in WKY and
      SD (P < 0.001). Tubular flow rate producing a half-maximal response (turning
      point) shifted to higher flow rates during VE, from 12 to 14 nl/min in SHR and
      from 15 to 19 nl/min in WKY. Administration of the AT1 receptor blocker
      candesartan (0.05 mg/kg iv) during sustained VE decreased TGF-mediated reductions
      in SFP in SHR and slightly increased the turning point in WKY. Nevertheless,
      other parameters of TGF activity were unaffected by AT1 receptor blockade. In
      conclusion, young SHR possess the ability to reset TGF activity in response to VE
      to a degree similar to compensatory adjustments in WKY. However, TGF remains
      enhanced in SHR during VE. ANG II and its action on AT1 receptors are in part
      responsible for the exaggerated SFP responses in young SHR during VE.

PMID- 10070165
TI  - Contribution of endothelin to renal vascular tone and autoregulation in the
      conscious dog.
AB  - Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the canine kidney
      and causes a decrease in renal blood flow (RBF) by stimulating the ETA receptor
      subtype. The aim of the present study was to investigate the role of endogenously
      generated ET-1 in renal hemodynamics under physiological conditions. In six
      conscious foxhounds, the time course of the effects of the selective ETA receptor
      antagonist LU-135252 (10 mg/kg iv) on mean arterial blood pressure (MAP), heart
      rate (HR), RBF, and glomerular filtration rate (GFR), as well as its effects on
      renal autoregulation, were examined. LU-135252 increased RBF by 20% (from 270 +/-
      21 to 323 +/- 41 ml/min, P < 0.05) and HR from 76 +/- 5 to 97 +/- 8 beats/min (P
      < 0. 05), but did not alter MAP, GFR, or autoregulation of RBF and GFR. Since a
      number of interactions between ET-1 and the renin-angiotensin system have been
      reported previously, experiments were repeated during angiotensin converting
      enzyme (ACE) inhibition by trandolaprilat (2 mg/kg iv). When ETA receptor
      blockade was combined with ACE inhibition, which by itself had no effects on
      renal hemodynamics, marked changes were observed: MAP decreased from 91 +/- 4 to
      80 +/- 5 mmHg (P < 0.05), HR increased from 85 +/- 5 to 102 +/- 11 beats/min (P <
      0.05), and RBF increased from 278 +/- 23 to 412 +/- 45 ml/min (P < 0.05). Despite
      a pronounced decrease in renal vascular resistance over the entire pressure range
      investigated (40-100 mmHg), the capacity of the kidneys to autoregulate RBF was
      not impaired. The GFR remained completely unaffected at all pressure levels.
      These results demonstrate that endogenously generated ET-1 contributes
      significantly to renal vascular tone but does not interfere with the mechanisms
      of renal autoregulation. If ETA receptors are blocked, then the vasoconstrictor
      effects of ET-1 in the kidney are compensated for to a large extent by an
      augmented influence of ANG II. Thus ET-1 and ANG II appear to constitute a major
      interrelated vasoconstrictor system in the control of RBF.

PMID- 10070166
TI  - Renal and hemodynamic effects of losartan in conscious dogs during controlled
      mechanical ventilation.
AB  - In 12 conscious dogs, we investigated whether the angiotensin II-receptor
      antagonist losartan increases renal sodium excretion and urine volume during
      controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In
      four experimental protocols, the dogs were extracellular volume (ECV) expanded
      (electrolyte solution, 0.5 ml. kg-1. min-1 iv) or not and received losartan (100
      micrograms. kg-1. min-1 iv) or not. They breathed spontaneously during the 1st
      and 4th hour and received CMV with positive end-expiratory pressure (mean airway
      pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs
      with losartan excreted approximately 18% more sodium (69 +/- 7 vs. 38 +/- 5
      micromol. min-1. kg-1) and 15% more urine during the 2 h of CMV because of a
      higher glomerular filtration rate (5.3 +/- 0.3 vs. 4.5 +/- 0.2 ml. min-1. kg-1)
      and the tubular effects of losartan. In the group without expansion, sodium
      excretion (2.0 +/- 0.6 vs. 2.6 +/- 1.0 micromol. min-1. kg-1) and glomerular
      filtration rate (3.8 +/- 0.3 vs. 3.8 +/- 0.4 ml. min-1. kg-1) did not change, and
      urine volume decreased similarly in both groups during CMV. Plasma vasopressin
      and aldosterone increased in both groups, and plasma renin activity increased
      from 4.9 +/- 0.7 to 7.8 +/- 1.3 ng ANG I. ml-1. h-1 during CMV in nonexpanded
      dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded
      dogs with losartan. In conclusion, losartan increases sodium excretion and urine
      volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease
      in mean arterial blood pressure and/or an increase in aldosterone and vasopressin
      during CMV attenuates the renal effects of losartan.

PMID- 10070167
TI  - AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured
      rat mesangial cells.
AB  - The present study examined how arginine vasopressin (AVP) affects nitric oxide
      (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were
      incubated with test agents and nitrite, and intracellular cGMP content, inducible
      nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess
      method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP
      inhibited lipopolysaccharide (LPS)- and interleukin-1beta (IL-1beta)-induced
      nitrite production in a dose- and time-dependent manner, with concomitant changes
      in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed
      by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also
      reproduced on LPS and interferon-gamma (IFN-gamma). Protein kinase C (PKC)
      inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite
      production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC),
      inhibitors of nuclear factor-kappaB, inhibited nitrite production, further
      inhibition by AVP was not observed. AVP did not show further inhibition of
      nitrite production with actinomycin D, an inhibitor of transcription, or
      cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS
      and IL-1beta-induced NO production through a V1 receptor. The inhibitory action
      of AVP involves both the activation of PKC and the transcription of iNOS mRNA in
      cultured rat GMC.

PMID- 10070168
TI  - Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in
      conscious dogs.
AB  - The aim of this study was to investigate the influence of the mean level and
      phasic modulation of NO on the dynamic autoregulation of renal blood flow (RBF).
      Transfer functions were calculated from spontaneous fluctuations of RBF and
      arterial pressure (AP) in conscious resting dogs for 2 h under control
      conditions, after NO synthase (NOS) inhibition [NG-nitro-L-arginine methyl ester
      hydrochloride (L-NAME)] and after L-NAME followed by a continuous infusion of an
      NO donor [S-nitroso-N-acetyl-DL-penicillamine (SNAP)]. After L-NAME (n = 7) AP
      was elevated, heart rate (HR) and RBF were reduced. The gain of the transfer
      function above 0.08 Hz was increased, compatible with enhanced resonance of the
      myogenic response. A peak of high gain around 0.03 Hz, reflecting oscillations of
      the tubuloglomerular feedback (TGF), was not affected. The gain below 0.01 Hz,
      was elevated, but still less than 0 dB, indicating diminished but not abolished
      autoregulation. After L-NAME and SNAP (n = 5), mean AP and RBF were not changed,
      but HR was slightly elevated. The gain above 0.08 Hz and the peak of high gain at
      0.03 Hz were not affected. The gain below 0.01 Hz was elevated, but smaller than
      0 dB. It is concluded that NO may help to prevent resonance of the myogenic
      response depending on the mean level of NO. The feedback oscillations of the TGF
      are not affected by NO. NO contributes to the autoregulation below 0.01 Hz due to
      phasic modulation independent of its mean level.

PMID- 10070169
TI  - ATP-mediated Ca2+ signaling in preglomerular smooth muscle cells.
AB  - We performed studies to determine the effect of extracellular ATP on the
      intracellular Ca2+ concentration ([Ca2+]i) in freshly isolated microvascular
      smooth muscle cells (MVSMC). Suspensions of preglomerular MVSMC were prepared by
      enzymatic digestion and loaded with fura 2. Single cells were studied using a
      microscope-based fluorescence spectrophotometer during superfusion of a
      physiological salt solution with 1.8 mM Ca2+ and during exposure to similar
      solutions containing ATP. Under control conditions, baseline [Ca2+]i averaged 107
      +/- 6 nM (n = 86 cells from 34 animals). ATP administration elicited
      concentration-dependent increases in [Ca2+]i. Exposure to ATP concentrations of
      1, 10, and 100 microM increased intracellular Ca2+ to peak concentrations of 133
      +/- 20, 338 +/- 37, and 367 +/- 35 nM, respectively (P < 0.05 vs. respective
      baseline). Steady-state [Ca2+]i increased to 113 +/- 15, 150 +/- 16 (P < 0.05 vs.
      baseline), and 180 +/- 12 nM (P < 0.05 vs. baseline) for the same groups. The
      [Ca2+]i response to ATP was also assessed in the absence of extracellular Ca2+
      and during blockade of L-type Ca2+ channels with diltiazem. In these studies,
      exposure to 100 microM ATP induced a transient peak increase in [Ca2+]i with the
      plateau phase being totally abolished under Ca2+-free conditions and markedly
      attenuated during Ca2+ channel blockade, respectively. These data indicate that
      ATP-mediated P2-receptor activation increases [Ca2+]i in freshly isolated
      preglomerular MVSMC by stimulating Ca2+ release from intracellular stores, in
      addition to stimulating the influx of extracellular Ca2+ through voltage-gated L
      type Ca2+ channels.

PMID- 10070170
TI  - ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity
      in IgA nephropathy.
AB  - Protein trafficking across the glomerular capillary has a pathogenic role in
      subsequent renal damage. Despite evidence that angiotensin-converting enzyme
      (ACE) inhibitors improve glomerular size-selectivity, whether this effect is
      solely due to ANG II blocking or if other mediators also play a contributory role
      is not clear yet. We studied 20 proteinuric patients with IgA nephropathy, who
      received either enalapril (20 mg/day) or the ANG II receptor blocker irbesartan
      (100 mg/day) for 28 days in a randomized double-blind study. Measurements of
      blood pressure, renal hemodynamics, and fractional clearance of neutral dextran
      of graded sizes were performed before and after 28 days of treatment. Both
      enalapril and irbesartan significantly reduced blood pressure over baseline. This
      reduction reached the maximum effect 4-6 h after drug administration but did not
      last for the entire 24-h period. Despite transient antihypertensive effect,
      proteinuria was effectively reduced by both treatments to comparable extents.
      Neither enalapril nor irbesartan modified the sieving coefficients of small
      dextran molecules, but both effectively reduced transglomerular passage of large
      test macromolecules. Theoretical analysis of sieving coefficients showed that
      neither drug affected significantly the mean pore radius or the spread of the
      pore-size distribution, but both importantly and comparably reduced the
      importance of a nonselective shunt pathway. These data suggest that antagonism of
      ANG II is the key mechanism by which ACE inhibitors exert their beneficial effect
      on glomerular size-selective function and consequently on glomerular filtration
      and urinary output of plasma proteins.

PMID- 10070171
TI  - In vitro effects of simvastatin on tubulointerstitial cells in a human model of
      cyclosporin nephrotoxicity.
AB  - To investigate the possibility that 3-hydroxy-3-methylglutaryl CoA (HMGCoA)
      reductase inhibitors ameliorate renal disease via direct effects on the
      tubulointerstitium, primary cultures of human proximal tubule cells (PTC) and
      renal cortical fibroblasts (CF) were exposed for 24 h to simvastatin (0.1-10
      micromol/l) under basal conditions and in the presence of 1,000 ng/ml of
      cyclosporin (CsA), which we have previously shown to promote in vitro
      interstitial matrix accumulation at least partially via activation of local
      cytokine networks. Simvastatin, in micromolar concentrations, engendered
      cholesterol-independent inhibition of CF and PTC thymidine incorporation and
      cholesterol-dependent suppression of PTC apical Na+/H+ exchange (NHE)
      (ethylisopropylamiloride-sensitive apical 22Na+ uptake). Similarly, CF secretion
      of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were depressed,
      whereas CF collagen synthesis ([3H]proline incorporation) and PTC secretion of
      the fibrogenic cytokines, transforming growth factor-beta1, and platelet-derived
      growth factor were unaffected. A lower concentration (0.1 micromol/l) of
      simvastatin did not affect any of the above parameters under basal conditions but
      completely prevented CsA-stimulated CF collagen synthesis (control, 6.6 +/- 0.6;
      CsA, 8.3 +/- 0.6; CsA+simvastatin, 6.2 +/- 0.5%; P < 0.05) and IGF-I secretion
      (89.5 +/- 16.6, 204.7 +/- 57.0, and 94.6 +/- 22.3 ng. mg protein-1. day-1,
      respectively; P < 0.05). The results suggest that simvastatin exerts direct
      cholesterol-dependent and -independent effects on the human kidney
      tubulointerstitium. HMGCoA reductase inhibitors may ameliorate interstitial
      fibrosis complicating CsA therapy via direct actions on human renal cortical
      fibroblasts.

PMID- 10070172
TI  - Potassium supplement upregulates the expression of renal kallikrein and
      bradykinin B2 receptor in SHR.
AB  - High potassium intake is known to attenuate hypertension, glomerular lesion,
      ischemic damage, and stroke-associated death. Our recent studies showed that
      expression of recombinant kallikrein by somatic gene delivery reduced high blood
      pressure, cardiac hypertrophy, and renal injury in hypertensive animal models.
      The aim of this study is to explore the potential role of the tissue kallikrein
      kinin system in blood pressure reduction and renal protection in spontaneously
      hypertensive rats (SHR) on a high-potassium diet. Young SHR were given drinking
      water with or without 1% potassium chloride for 6 wk. Systolic blood pressure was
      significantly reduced beginning at 1 wk, and the effect lasted for 6 wk in the
      potassium-supplemented group compared with that in the control group. Potassium
      supplement induced 70 and 40% increases in urinary kallikrein levels and renal
      bradykinin B2 receptor density, respectively (P < 0.05), but did not change serum
      kininogen levels. Similarly, Northern blot analysis showed that renal kallikrein
      mRNA levels increased 2.7-fold, whereas hepatic kininogen mRNA levels remained
      unchanged in rats with high potassium intake. No difference was observed in beta
      actin mRNA levels in the kidney or liver of either group. Competitive RT-PCR
      showed a 1.7-fold increase in renal bradykinin B2 receptor mRNA levels in rats
      with high potassium intake. Potassium supplement significantly increased water
      intake, urine excretion, urinary kinin, cAMP, and cGMP levels. This study
      suggests that upregulation of the tissue kallikrein-kinin system may be
      attributed, in part, to blood pressure-lowering and diuretic effects of high
      potassium intake.

PMID- 10070173
TI  - Comparison of budesonide Turbuhaler with budesonide aqua in the treatment of
      seasonal allergic rhinitis. Rhinocort Study Group.
AB  - OBJECTIVE: To compare the effect of budesonide Turbuhaler 400 microg/day with
      budesonide aqua 256 microg/day in the treatment of seasonal allergic rhinitis
      (SAR). Secondarily to ascertain patients' preferences for the two nasal devices
      and to assess quality of life. DESIGN: Randomized, multicentre, double-blind,
      double- dummy, parallel groups study. SETTING: Private practices and hospital
      clinics in Ontario, Quebec and Manitoba. POPULATION: Two hundred and eighty-four
      out-patients with SAR, who were symptomatic during the ragweed season,
      volunteered for enrolment (243 randomized). RESULTS: Mean daily nasal symptom
      scores were significantly reduced with treatment. There were no statistically
      significant changes from baseline for eye symptoms. Most patients (more than 80%)
      achieved substantial control of their symptoms with budesonide. The most common
      nasal and non-nasal adverse events for both groups were epistaxis and headache.
      Turbuhaler was easier to use and more convenient to carry, had less of an
      unpleasant taste, and caused less nasal irritation than the aqua spray. More than
      twice as many patients preferred Turbuhaler to the aqua spray (69% versus 31%).
      Improvement in quality of life from baseline to clinic visits was statistically
      significant in both groups. CONCLUSION: Once daily use of 256 mg of budesonide
      aqua and 400 mg of budesonide Turbuhaler are equally safe and efficacious in the
      treatment of SAR. Patients preferred the budesonide powder formulation delivered
      via Turbuhaler two to one over the aqua formulation.

PMID- 10070174
TI  - The patient level cost of asthma in adults in south central Ontario. Pharmacy
      Medication Monitoring Program Advisory Board.
AB  - OBJECTIVE: To assess the annual cost of asthma per adult patient from the
      perspectives of society, the Ontario Ministry of Health and the patient. DESIGN:
      Prospective cost of illness evaluation. SETTING: Ambulatory out-patients residing
      in southern central Ontario. POPULATION STUDIED: Nine hundred and forty patients
      with asthma over 15 years of age studied between May 1995 and April 1996. OUTCOME
      MEASURES: Direct costs, such as respiratory-related visits to general/family
      practitioners, respiratory specialists, emergency rooms, hospital admissions,
      laboratory tests, prescription medications, dispensing fees, devices and out-of
      pocket expenses, were calculated. Indirect costs, such as absences from work or
      usual activities, and travel and waiting time, were studied. MAIN RESULTS:
      Unadjusted annual costs were $2,550 per patient. Hospitalizations and medications
      each accounted for 22% of the total cost and indirect costs 50% of the total
      costs. More severe disease, older age, smoking, drug plan availability and
      retirement were significant predictors of costs. Annual costs per patient varied
      from $1,255 (95% CI $1,061 to $1,485) in young nonsmokers with no drug plan and
      mild disease to $5,032 (95% CI $4,347 to $5,825) in older smokers with drug plans
      and severe disease. Clinically important reductions in the quality of life
      occurred with increasing severity. CONCLUSIONS: Interventions aimed at reducing
      productivity losses, admissions to hospital and medication costs may result in
      savings to society, the provincial government and the patient. The quality of
      policy and allocation decisions may be enhanced by cost of illness estimates that
      are comprehensive, precise and incorporate multiple perspectives.

PMID- 10070175
TI  - Predictors of longitudinal changes in pulmonary function among swine confinement
      workers.
AB  - OBJECTIVE: To determine predictors of longitudinal changes in pulmonary function
      in swine confinement workers. DESIGN: Longitudinal study conducted from November
      1989 to June 1991 and January 1994 to May 1995. SETTING: Swine confinement
      workers in Saskatchewan. PARTICIPANTS: Forty-two swine confinement workers who
      were studied in 1989/90 and studied again in 1994/95. RESULTS: Of 98 male swine
      confinement workers (mean age SD 36.3 11.1 years) studied at baseline, 42 were
      studied again five years following. Complete information on baseline across-shift
      pulmonary function (preshift forced expiratory volume in 1 s [FEV1], forced vital
      capacity [FVC], and every 2 h FEV1 and FVC during the shift), and five-year
      follow-up pulmonary function (with FEV1 and FVC) were available on all 42
      subjects. Mean across-shift changes (preshift measurement to last measurement of
      the day) at baseline were -159. 8 61.7 mL in FEV1 and -35.3 65.6 mL in FVC. Mean
      annual rate change between baseline and follow-up for FEV1 was -53.9 61.7 mL/year
      and for FVC -48.9 71.6 mL/year. After adjusting for age, height, smoking and
      hours spent in the barn, the baseline across-shift change in FEV1 and FVC was a
      significant predictor of annual rate change in FEV1 (P=0.01) and FVC (P=0.02),
      respectively. To determine the effects of indoor air quality on longitudinal lung
      function decline, indoor air environmental measurements were analysed. Complete
      information on respiratory health and indoor air quality was available on 34 of
      the 42 subjects. Assessment of indoor environment of swine barns included a
      summer and winter measurement for airborne dust, gases and endotoxin levels.
      After adjusting for age, height, smoking, ammonia and hours spent in the barn,
      the endotoxin level (Eu/mg)was a significant predictor of annual rate change for
      FEV1 but not FVC. CONCLUSIONS: These results suggest that shift change is an
      important predictor of longitudinal changes in lung function in swine confinement
      workers and that endotoxin exposures may mediate annual decline in FEV1 in these
      workers.

PMID- 10070176
TI  - Ventilatory care in status asthmaticus.
AB  - Asthma continues to pose a significant medical problem in terms of both morbidity
      and mortality. A number of patients with a severe exacerbation of asthma fail
      medical therapy and require urgent intubation and mechanical ventilation. New
      modalities of ventilatory support, including noninvasive ventilation, have been
      shown to provide effective ventilation even in the presence of severe
      bronchoconstriction. An intrinsically high level of auto positive end-expiratory
      pressure in these patients requires a precise balance between respiratory
      frequency, tidal volume and inspiratory flow rates. Pressure support ventilation
      reduces the risk of barotrauma and lowers the work of breathing in these
      patients. Adjuvant therapy with inhaled anesthetics and bronchoalveolar lavage
      may also be indicated in patients requiring high pressures to achieve adequate
      ventilation.

PMID- 10070177
TI  - Calcium handling in airway smooth muscle: mechanisms and therapeutic
      implications.
AB  - Calcium plays a central role in the activation of many cellular processes,
      including the most relevant end-point in airway smooth muscle physiology:
      contraction. For this reason, the cytosolic concentration of calcium is tightly
      controlled by an elaborate array of mechanisms. The latter include multiple entry
      pathways from the extracellular space, a pump on the membrane that extrudes
      calcium out of the cell, an internal pump that sequesters calcium into an
      intracellular pool and at least two types of release sites from which sequestered
      calcium can be released back into the cytosol; all of these mechanisms are
      tightly regulated by second messenger-signalling pathways. Understanding of the
      relationship between calcium handling and contraction ('excitation-contraction
      coupling') has progressed from a mechanism in which activation of voltage
      dependent calcium channels plays a central role (as in skeletal muscle) to a
      mechanism in which a small localized signalling event triggers a massive release
      of internal calcium (as in cardiac muscle) to a more complicated model in which
      the internal calcium pool divides the cytosol into two physiologically distinct
      spaces where the cytosolic concentration of calcium is regulated independently
      (as in vascular smooth muscle). The changes that may occur in calcium-handling
      pathways in asthma and the opportunities for novel approaches to the treatment of
      asthma are also discussed.

PMID- 10070178
TI  - A pediatric case of pigeon breeder's disease in Nova Scotia.
AB  - Pigeon breeder's disease has been reported sporadically in the pediatric
      population since it was first described in children in 1967. Because of its
      infrequent occurrence in children, a high level of suspicion is often required
      before a diagnosis is made. A case of pigeon breeder's disease in a child in Nova
      Scotia, where the disease is virtually unseen or at least unrecognized, is
      described. The need for prompt recognition of the condition is paramount because
      its complications may be irreversible.

PMID- 10070180
TI  - Adherence to physician training guidelines for pediatric transesophageal
      echocardiography affects the outcome of patients undergoing repair of congenital
      cardiac defects.
AB  - Intraoperative echocardiography is widely accepted as being useful during a
      variety of cardiac surgical procedures. Several applications have been reported
      during the repair of congenital cardiac defects. National organizations,
      including the Society of Pediatric Echocardiography and the American Society of
      Echocardiography, have published guidelines for the provision of at least minimum
      standards of training and quality for a variety of cardiac ultrasonography
      procedures. Few data exist concerning whether adherence to such guidelines
      affects the performance of ultrasonography studies or patient outcome. This study
      is an outcome-based analysis of intraoperative transesophageal echocardiography
      performed during repair of congenital cardiac defects during 5-month periods in 2
      different years. In year 1, examinations were performed by physicians who met the
      guidelines for pediatric transesophageal echocardiography published by the
      American Society of Echocardiography. Those performing examinations in year 2 did
      not meet those guidelines. Significant differences between the years were found
      for adequacy of echocardiographic recordings, return to bypass for further
      surgery based on echocardiographic results, and prevalence and detection of
      significant residual problems by intraoperative echocardiography. It is concluded
      that patient outcome is affected beneficially when intraoperative transesophageal
      echocardiography is performed by physicians who meet the published guidelines,
      and whose sole responsibility is the performance of echocardiography.

PMID- 10070179
TI  - Recurrence of intravenous talc granulomatosis following single lung
      transplantation.
AB  - Advanced pulmonary disease is an unusual consequence of the intravenous injection
      of oral medications, usually developing over a period of several years. A number
      of patients with this condition have undergone lung transplantation for
      respiratory failure. However, a history of drug abuse is often considered to be a
      contraindication to transplantation in the context of limited donor resources. A
      patient with pulmonary talc granulomatosis secondary to intravenous
      methylphenidate injection who underwent successful lung transplantation and
      subsequently presented with recurrence of the underlying disease in the
      transplanted lung 18 months after transplantation is reported.

PMID- 10070181
TI  - Three-dimensional color Doppler: a new approach for quantitative assessment of
      mitral regurgitant jets.
AB  - Color Doppler echocardiography does not provide adequate information about the
      severity of mitral regurgitation in patients with eccentric mitral regurgitation.
      We have developed a new procedure for 3-dimensional (3D) color Doppler
      reconstruction and for segmentation of regurgitant jets. The volume of
      regurgitant jets was compared with jet area in 63 patients with mitral
      regurgitation. Mitral regurgitation was assessed by angiography, regurgitant
      fraction and volume by pulsed Doppler, JA by planimetry, and JV by 3-dimensional
      Doppler. Twenty-eight patients with central jets were compared with 35 patients
      with eccentric jets. In the patients with eccentric jets, JV showed significant
      correlations with regurgitant volume (r = 0.90; P <.01) and regurgitant fraction
      (r = 0.76; P < .01) and was able to separate groups with different degrees of
      mitral regurgitation (P <.01). Three-dimensional Doppler revealed origin,
      direction, and spatial spreading of complex jet geometry. JV, a new parameter of
      mitral regurgitation, was also capable of quantifying asymmetrical jets.

PMID- 10070182
TI  - Noninvasive assessment of coronary flow reserve with transthoracic signal
      enhanced Doppler echocardiography.
AB  - OBJECTIVES: The feasibility of noninvasive assessment of coronary flow reserve
      (CFR) in the distal left anterior descending artery (LAD) with echocardiography
      enhanced transthoracic pulsed wave Doppler guided by high-resolution
      transthoracic color Doppler (TTCD) was investigated. The results were compared
      with the degree of coronary diameter stenosis obtained during cardiac
      catheterization. BACKGROUND: Assessment of CFR has proven to be useful in the
      selection of patients undergoing invasive treatment of coronary artery disease
      and in estimating their prognosis. However, CFR could only be determined
      invasively in everyday practice during catheterization procedures. Recent
      development of high-resolution TTCD allows transthoracic visualization of distal
      LAD and supra-apical intramyocardial perforator branches and noninvasive
      measurement of CFR with pulsed wave Doppler technique. METHODS: CFR was
      determined by measuring the ratio of pulsed wave Doppler time velocity integral
      during adenosine-induced hyperemia (140 microgram/kg/min intravenously) to
      baseline value. If the baseline Doppler signal of LAD flow was insufficient, an
      echocardiography (echo) enhancer (Levovist) was used. Forty-five patients were
      examined by TTCD (7-MHz B-mode, 5-MHz color Doppler, and 3.5-MHz pulsed wave
      Doppler) after coronary angiography had been performed. Group 1 consisted of 15
      patients without heart disease, group 2 of 15 patients with 50% to 85% isolated
      LAD diameter stenosis, and group 3 of 15 patients with >85% LAD diameter
      stenosis. RESULTS: Peripheral LAD coronary flow at baseline condition was
      assessed in 40 (88%) patients with TTCD. CFR could be quantified in 36 (80%) of
      the 45 patients: in 18 patients without echo enhancer, and in 18 patients with
      echo-enhancing agent. CFR could not be assessed in 9 (20%) patients. CFR in the
      various groups was as follows: group 1, 3. 13 +/- 0.57; group 2, 2.23 +/- 0.20
      (vs group 1: P <.01); and group 3, 1.64 +/- 0.30 (vs group 2: P <.02).
      CONCLUSION: CFR in the LAD can be determined in 80% of patients with pulsed wave
      Doppler guided by high-resolution TTCD combined with intravenously administered
      echo-enhancing agent.

PMID- 10070183
TI  - Regional wall motion assessment in stress echocardiography by tissue Doppler
      bull's-eyes.
AB  - Quantification of regional myocardial wall velocities is needed in stress
      echocardiography for transition from subjective to quantitative assessment.
      Tissue Doppler allows quantitation of wall velocities, but interpretation is
      difficult and angle-dependent. Calculating the ratios of velocities with similar
      angles to the beam may overcome angle dependency. We measured left ventricular
      wall velocities during stress echocardiography with tissue Doppler. Regional peak
      systolic and early (E) and late (A) diastolic velocities were constructed in a
      "bull's-eye" format. Regional stress/rest and E/A ratios were calculated. Bull's
      eye map construction demanded only minimal manual interaction, and the maps
      showed the left ventricular velocity distribution, simplifying wall motion
      reading markedly. Still, apical velocities appeared lower as a result of Doppler
      angle-dependency. With velocity ratios, angle-dependency was no longer noted. In
      stress echocardiography, wall motion abnormalities at rest and contractility
      changes with dobutamine became readily apparent. Bull's-eye display of
      quantitative tissue Doppler velocity allows rapid assessment of regional wall
      motion. Calculating the ratio of regional velocities circumvents the angle
      dependency of Doppler. This novel technique has the potential for simplified and
      automated quantitative analysis in stress echocardiography.

PMID- 10070184
TI  - Evaluation of left ventricular diastolic function when mitral E and A waves are
      completely fused: role of assessing mitral annulus velocity.
AB  - Mitral inflow parameters have been used most widely in the evaluation of left
      ventricular (LV) diastolic function. However, when the mitral E and A waves are
      completely fused, mitral inflow parameters cannot provide information about the
      LV diastolic function. LV filling pressure, mitral inflow, mitral annulus
      velocity, and tau (tau) were measured in 59 patients with sinus rhythm when
      mitral E and A waves were completely fused with right atrial pacing. When mitral
      E and A waves were completely fused, tau correlated with the peak fused mitral
      annulus velocity (r = -0.60, P <.001), and peak fused mitral annulus velocity of
      less than 12.5 cm/s best discriminated prolonged (>/=50 ms) from normal tau, with
      a sensitivity of 78% and specificity of 69%. The peak fused mitral inflow
      velocity to peak fused mitral annulus velocity ratio correlated with LV filling
      pressure (r = 0.62, P <.001). A ratio of at least 8, could predict elevated LV
      filling pressure (>/=15 mm Hg) with a sensitivity of 65% and specificity of 74%.
      In conclusion, even when mitral E and A waves are completely fused, mitral
      annulus velocity can be used in the evaluation of LV diastolic function.

PMID- 10070185
TI  - Quantitative evaluation of left ventricular function in a TransgenicMouse model
      of dilated cardiomyopathy with 2-dimensional contrast echocardiography.
AB  - The study of transgenic mouse models of human cardiovascular disease has been
      limited by the small size and high heart rate of the mouse heart. Advances in
      digital echocardiographic imaging equipment have provided the high spatial and
      temporal resolution necessary for 2-dimensional (2D) in vivo imaging of the mouse
      heart. The goal of this study was to test the use of contrast-enhanced 2D
      echocardiography to quantitatively assess left ventricular (LV) size and function
      in normal and transgenic mice with dilated cardiomyopathy. Images were obtained
      with a 12-MHz broadband transducer in the parasternal short-axis view in 8
      control mice and 8 transgenic mice with dilated cardiomyopathy resulting from
      expression of a dominant-negative CREB transcription factor in the heart. LV
      opacification was achieved with injections of human albumin microspheres,
      injectable suspension (Optison) (15 to 30 microliter bolus). LV area was measured
      throughout the cardiac cycle with manual frame-by-frame tracing of the
      endocardial boundary. End-systolic and end-diastolic areas (ESA and EDA) were
      measured and fractional area change (FAC) calculated in both groups at baseline
      and during administration of dobutamine (40 microgram/kg/min intravenously). High
      quality 2D images, which yielded LV area over time waveforms, were obtained in
      all mice. Under baseline conditions, ESA was significantly higher and FAC lower
      in the transgenic mice compared with their controls. During administration of
      dobutamine, normal mice had significantly smaller ESA and significantly larger
      FAC compared with baseline conditions, whereas this trend did not reach
      significance in the transgenic mice. In summary, quantitative assessment of LV
      size and function may be achieved with contrast-enhanced 2D echocardiographic
      imaging. This technique promises to facilitate studies of pathophysiology in
      murine models of human cardiovascular disease.

PMID- 10070186
TI  - Calcified right atrial mass in a woman receiving long-term intravenous phosphate
      therapy.
AB  - Right atrial masses are easily seen by 2-dimensional echocardiography and may
      represent primary tumors, secondary tumor invasion of the right atrium, tricuspid
      valve vegetations, or atrial thrombi. Calcification of right atrial masses is
      uncommon but easily identified by 2-dimensional echocardiography because of the
      high echogenicity of calcium deposits. We describe a patient with a heavily
      calcified right atrial thrombus caused by an indwelling central venous catheter
      and long-term intravenous phosphate infusion.

PMID- 10070187
TI  - Left ventricular apical diastolic collapse: an unusual echocardiographic marker
      of postoperative cardiac tamponade.
AB  - A 37-year-old woman was evaluated for signs and symptoms of cardiac tamponade 11
      days after mitral valve replacement and tricuspid valve repair. The transthoracic
      echocardiogram showed a large, compartmentalized pericardial effusion that
      resulted in left ventricular apical diastolic collapse. Also noted were right
      ventricular posterior wall diastolic collapse and hemodynamic findings consistent
      with cardiac tamponade. This case highlights the atypical echocardiographic
      findings in patients with pericardial effusions after cardiac surgery.

PMID- 10070188
TI  - Anomalous origin of the right coronary artery from the left sinus of valsalva:
      transthoracic echocardiographic diagnosis.
AB  - Anomalous origin of the right coronary artery from the left sinus of Valsalva is
      a rare congenital defect that can be difficult to diagnose by echocardiography.
      We describe an infant with a ventricular septal defect that was diagnosed
      prospectively by transthoracic echocardiography as an anomalous origin of the
      right coronary artery from the left sinus of Valsalva. Subcostal imaging and
      Doppler color flow mapping were instrumental in the echocardiographic diagnosis
      of this unusual coronary abnormality.

PMID- 10070189
TI  - ERISA shield is cracked; HMOs open to liability. Improves legal atmosphere for
      physicians, patients. Employee Retirement Income Security Act.

PMID- 10070190
TI  - Litigation center is voice of medicine in nation's courts.

PMID- 10070191
TI  - Aetna/Prudential deal would impact PA patients, employers.

PMID- 10070193
TI  - Retrospective program boasts new addition.

PMID- 10070192
TI  - Court victory offers new protections to third parties.

PMID- 10070194
TI  - Court decision emphasizes need for specialized addiction treatment.

PMID- 10070195
TI  - Similarity of the perimeters in the Ebbinghaus illusion.
AB  - Coren and Miller (1974) and Coren and Enns (1993) argued that the magnitude of
      the Ebbinghaus illusion is a function of the rated or conceptual similarity of
      the inducing objects to the test object. In three experiments, we examined the
      convergence between conceptual similarity and illusion magnitude. The first
      failed to find support for this parallel. Two further experiments yielded support
      for an alternative hypothesis that the magnitude of the Ebbinghaus illusion is a
      function of the similarity of the perimeters of the inducing object to the test
      object. The similarity of the centers had no effect. These results suggest that
      the information used to estimate size is computed earlier in the visual system
      than suggested by Coren and colleagues and apparently does not involve the use of
      conceptual information.

PMID- 10070196
TI  - Subjective staircase: a multiple wallpaper illusion.
AB  - When observers binocularly fixate on an inclined sheet of paper with equally
      spaced dots, an apparent "staircase" is seen. We varied the inclination of the
      sheet, the spacing among the dots, and the viewing distance. The results indicate
      that (1) as the space and the inclination decreased, the number of apparent steps
      increased and the height of apparent steps decreased, and (2) as the distance and
      the inclination increased, the number of apparent steps decreased, and eventually
      the illusion disappeared. The nearest-neighbor rule and the extent of the
      vertical horopter inclination explain the characteristics of the illusion.

PMID- 10070197
TI  - The surface-weight illusion: on the contribution of grip force to perceived
      heaviness.
AB  - Previous psychophysical studies have shown that an object, lifted with a
      precision grip, is perceived as being heavier when its surface is smooth than
      when it is rough. Three experiments were conducted to assess whether this surface
      weight illusion increases with object weight, as a simple fusion model suggests.
      Experiment 1 verified that grip force increases more steeply with object weight
      for smooth objects than for rough ones. In Experiment 2, subjects rated the
      weight of smooth and rough objects. Smooth objects were judged to be heavier than
      rough ones; however, this effect did not increase with object weight. Experiment
      3 employed a different psychophysical method and replicated this additive effect,
      which argues strongly against the simple fusion model. The whole pattern of
      results is consistent with a weighted fusion model in which the sensation of grip
      force contributes only partially to the perceived heaviness of a lifted object.

PMID- 10070198
TI  - Object-based visual selective attention and perceptual organization.
AB  - We report the results of four experiments that were conducted to examine both the
      representations that provide candidate entities available for object-based
      attentional selection and the influence of bottom-up factors (i.e., geometric and
      surface characteristics of objects) and top-down factors (i.e., context and
      expectancies) on the selection process. Subjects performed the same task in each
      of the experiments. They were asked to determine whether two target properties, a
      bent end and an open end of a wrench, appeared in a brief display of two
      wrenches. In each experiment, the target properties could occur on a single
      wrench or one property could occur on each of two wrenches. The question of
      central interest was whether a same-object effect (faster and/or more accurate
      performance when the target properties appeared on one vs. two wrenches) would be
      observed in different experimental conditions. Several interesting results were
      obtained. First, depending on the geometric (i.e., concave discontinuities on
      object contours) and surface characteristics (i.e., homogeneous regions of color
      and texture) of the stimuli, attention was preferentially directed to one of
      three representational levels, as indicated by the presence or absence of the
      same-object effect. Second, although geometric and surface characteristics
      defined the candidate objects available for attentional selection, top-down
      factors were quite influential in determining which representational level would
      be selected. Third, the results suggest that uniform connectedness plays an
      important role in defining the entities available for attention selection. These
      results are discussed in terms of the manner in which attention selects objects
      in the visual environment.

PMID- 10070199
TI  - Scene-based and object-centered inhibition of return: evidence for dual orienting
      mechanisms.
AB  - We investigated whether inhibition of return (IOR) could be observed in location
      based, scene-based, and object-centered frames of reference. IOR was found to
      move both with a separate cued object (scene-based) and with a location within a
      single rotating object (object-centered). Importantly, however, IOR was also
      associated with the environmental location cued when cuing was of a separate
      object (scene-based), whereas facilitation of the cued location was found when
      cuing was of a component within an object. These results suggest that location is
      of central importance to scene-based representations of separate objects, which
      appear to be encoded in viewer-centered coordinates, whereas environmental locus
      is of little relevance when attention orients within a single object. The results
      also provide further evidence for the coexistence of both excitation and
      inhibition associated with uninformative exogenous cues.

PMID- 10070200
TI  - Limitations in attending to a feature value for overriding stimulus-driven
      interference.
AB  - Six experiments were conducted to examine the effect of knowledge of a target for
      overriding stimulus-driven interference in simple search tasks (Experiments 1-3)
      and compound search tasks (Experiments 4-6). In simple search when the target
      differed from nontargets in orientation, a singleton distractor that had an
      orientation equivalent to that of a target interfered with search for the target.
      When the singleton distractor was less salient than the target with respect to
      the target-defining feature, it still caused interference. Such within
      dimensional, nonsaliency-based interference also occurred in compound search
      tasks. In contrast, no interference occurred when a singleton distractor was
      defined in cross-dimension in a simple search task. When a compound search task
      was used, the salient distractor interfered with the search for a less salient
      target. These results are discussed in terms of their applicability to existing
      models and the limitations of top-down penetrability of a feature processing
      stage.

PMID- 10070201
TI  - Effect of masker level on infants' detection of tones in noise.
AB  - In adult listeners, the signal-to-noise ratio at masked threshold remains
      constant with increases in masker level over a wide range of stimulus conditions.
      This relationship was examined in 7-month-old infants by obtaining masked
      thresholds for .5- and 4-kHz tones presented in four levels of continuous masking
      noise. Adults were also tested for comparison. Masker spectrum levels ranged from
      5 to 35 dB/Hz for .5-kHz tones, and from -5 to 25 dB/Hz for 4-kHz stimuli.
      Thresholds were determined for stimuli of both 10 and 100 msec in duration. The
      results indicated that infants' performance was more adult-like for 4-kHz
      stimuli. Although mean thresholds for both 10- and 100-msec, 4-kHz tones were
      approximately 7 dB higher in infants than in adults, E/N0 at threshold remained
      essentially constant over the 30-dB range of maskers employed. By contrast,
      infants' thresholds for .5-kHz tones were exceptionally high at lower levels of
      the masker. Threshold E/N0 decreased significantly as masker level increased from
      5 to 35 dB/Hz, and this decrease was significantly greater for 10- than for 100
      msec stimuli. Temporal summation of .5-kHz tones, measured as the difference
      between thresholds obtained at the two signal durations, was greater for infants
      than for adults at low levels of the masker. However, because infants' thresholds
      improved more rapidly with level for 10- than for 100-msec tones, age differences
      in temporal summation were no longer significant when masker spectrum level was
      35 dB/Hz. These results suggest that the relationship between signal-to-noise
      ratio at masked threshold and level of the masker is dependent on both signal
      frequency and duration during infancy.

PMID- 10070202
TI  - Fitting the psychometric function.
AB  - A constrained generalized maximum likelihood routine for fitting psychometric
      functions is proposed, which determines optimum values for the complete parameter
      set--that is, threshold and slope--as well as for guessing and lapsing
      probability. The constraints are realized by Bayesian prior distributions for
      each of these parameters. The fit itself results from maximizing the posterior
      distribution of the parameter values by a multidimensional simplex method. We
      present results from extensive Monte Carlo simulations by which we can
      approximate bias and variability of the estimated parameters of simulated
      psychometric functions. Furthermore, we have tested the routine with data
      gathered in real sessions of psychophysical experimenting.

PMID- 10070203
TI  - Effects of auditory stimulus intensity on response force in simple, go/no-go, and
      choice RT tasks.
AB  - In four experiments, increasing the intensities of both relevant and irrelevant
      auditory stimuli was found to increase response force (RF) in simple, go/no-go,
      and choice reaction time (RT) tasks. These results raise problems for models that
      localize the effects of auditory intensity on purely perceptual processes,
      indicating instead that intensity also affects motor output processes under many
      circumstances. In Experiment 1, simple RT, go/no-go, and choice RT tasks were
      compared, using the same stimuli for all tasks. Auditory stimulus intensity
      affected both RT and RF, and these effects were not modulated by task. In
      Experiments 2-4, an irrelevant auditory accessory stimulus accompanied a relevant
      visual stimulus, and the go/no-go and choice tasks were used. The intensity of
      the irrelevant auditory accessory stimulus was found to affect RT and RF,
      although the sizes of these effects depended somewhat on the temporal
      predictability of the accessory stimulus.

PMID- 10070204
TI  - Differential effects of shared attention on perception of heading and 3-D object
      motion.
AB  - When a person moves in a straight line through a stationary environment, the
      images of object surfaces move in a radial pattern away from a single point. This
      point, known as the focus of expansion (FOE), corresponds to the person's
      direction of motion. People judge their heading from image motion quite well in
      this situation. They perform most accurately when they can see the region around
      the FOE, which contains the most useful information for this task. Furthermore, a
      large moving object in the scene has no effect on observer heading judgments
      unless it obscures the FOE. Therefore, observers may obtain the most accurate
      heading judgments by focusing their attention on the region around the FOE.
      However, in many situations (e.g., driving), the observer must pay attention to
      other moving objects in the scene (e.g., cars and pedestrians) to avoid
      collisions. These objects may be located far from the FOE in the visual field. We
      tested whether people can accurately judge their heading and the three
      dimensional (3-D) motion of objects while paying attention to one or the other
      task. The results show that differential allocation of attention affects people's
      ability to judge 3-D object motion much more than it affects their ability to
      judge heading. This suggests that heading judgments are computed globally,
      whereas judgments about object motion may require more focused attention.

PMID- 10070205
TI  - Symmetry and elongation of objects influence perceived direction of translational
      motion.
AB  - Five experiments were conducted to examine how perceived direction of motion is
      influenced by aspects of shape of a moving object such as symmetry and
      elongation. Random polygons moving obliquely were presented on a computer screen
      and perceived direction of motion was measured. Experiments 1 and 2 showed that a
      symmetric object moving off the axis of symmetry caused motion to be perceived as
      more aligned with the axis than it actually was. However, Experiment 3 showed
      that motion did not influence perceived orientation of symmetry axis. Experiment
      4 revealed that symmetric shapes resulted in faster judgments on direction of
      motion than asymmetric shapes only when the motion is along the axis. Experiment
      5 showed that elongation causes a bias in perceived direction of motion similar
      to effects of symmetry. Existence of such biases is consistent with the
      hypothesis that in the course of evolution, the visual system has been adapted to
      regularities of motion in the animate world.

PMID- 10070206
TI  - The effects of stereoscopic depth on completion.
AB  - Stereoscopic depth has a critical effect on completion of partially occluded
      figures. However, it has not strictly been distinguished whether the effect is
      direct or indirect through alteration of contour segmentation or parsing. Here, I
      report that stereoscopic depth does not influence completion of partially
      occluded figures when parsing is unambiguous from motion cues. This is consistent
      with the present proposal that stereoscopic depth does not have a unique role in
      completion and that it is one of the cues to contour segmentation or parsing,
      which in turn influences completion and surface representation, like motion,
      shape, or transparency.

PMID- 10070207
TI  - Does symmetry structure facilitate the depth separation between stereoscopically
      overlapped dot planes?
AB  - In the present study, we dealt with the problem of whether a symmetrical
      structure can influence the discrimination of the depth separation of overlapped
      dot planes. We investigated this problem with the use of both direct and indirect
      methods. In the direct method, we presented three or two overlapped dot planes
      consisting of symmetrical or random dots. The subjects were required to
      discriminate three overlapped from two overlapped planes. In the indirect method,
      the subjects were required to discriminate the depth positions of a target dot
      (or a pair of dots) that disappeared during stimulus presentation. Our results,
      obtained in three experiments, showed that the discrimination performance
      improved and reached a perfect level in the direct method and a modest plateau
      level in the indirect method with increasing relative disparity between the two
      outer planes, irrespective of whether the dot pattern had a symmetrical structure
      or not. These results suggest that a detection process for symmetry structure on
      a two-dimensional plane in three-dimensional space will not have a direct or an
      indirect connection (e.g., via a feedback loop) to a process involved in the
      depth separation.

PMID- 10070208
TI  - Prism adaptation to dynamic events.
AB  - In the present study, we explored adaptation to prism-displaced dynamic and
      static events under conditions of minimal information. Many of our interactions
      with the world are dynamic and involve reaching for or intercepting moving
      objects. The consequences (or feedback) of those interactions entail the presence
      or absence of physical contact with the moving objects. In this study, humans
      learned, with only heptic feedback, to intercept optically displaced falling
      balls. To eliminate visual feedback, the falling balls disappeared behind an
      occluder (which systematically varied in size across groups) prior to either
      striking or missing a subject's hand. As occluder size decreased, adaptation
      increased. With minimum occluder sizes, the greatest adaptation occurred around
      the training position, and adaptation decreased as distance between training and
      testing positions increased. The results can best be described in terms of a
      generalization gradient centered around the training position. This
      generalization gradient was not present when subjects were trained with
      ecologically similar static arrays. Implications for models of adaptation are
      discussed.

PMID- 10070209
TI  - Lateral masking: limitations of the feature interaction account.
AB  - Recognition performance for a target letter embedded in a string of characters is
      worse than that for targets presented in isolation. This lateral masking (LM)
      effect is known to depend on target eccentricity and spacing between target and
      flankers (Bouma, 1970), indicating that LM arises in early visual processing due
      to interactions among visual features. The feature interaction account would
      predict that flankers consisting of similar features produce similar LM effects
      and that differences in LM produced by different types of flanker diminish with
      increasing target eccentricity and decreasing spacing. However, in a series of
      six experiments, this prediction was shown not to be true. Flankers that did not
      access a higher level code (e.g., pseudoletters or rotated letters) produced more
      LM than standard letter flankers. Moreover, effects of different flanker types
      were most pronounced for medium target eccentricities and medium spacings for
      which recognition performance scores ranged between 40% and 60%.

PMID- 10070210
TI  - Mechanosensitivity as an integrative system in heart: an audit.
AB  - This review examines a manifold of apparently loosely linked observations and
      mechanisms, from membrane to man, and assembles them to support the notion that
      mechanoelectric transduction is an integrative regulatory system in the heart.
      For this, the assemblage has to satisfy, at least to some extent, criteria that
      apply to other integrative regulatory systems such as the endocrine and nervous
      systems. The integrative effectors in the endocrine system are chemical linkages,
      circulating hormones: in the nervous system the linkage is a network of cables,
      nerve conduction and neurotransmitters. Mechanical integration is would be
      effected through mechanical machinery, cardiac contractile and hydraulic function
      with attendant stress and strain transmitted via "tensegrity". This can, through
      the cytoskeleton, begin with membrane integrins and transmit intracellularly for
      example via F actins to reach the rest of the membranous integrins. Further
      transmission to the organ is via cell-to-cell adhesion complexes and the
      extracellular matrix. This tensegrity facilitates integration of force and strain
      changes from area to area. In consequence, and analogous to the neurendocrine
      system, mechanoelectric transduction should, and does (1) operate at the
      molecular or membrane level--this would be via mechanotransducers affecting
      transmembrane ionic flow; (2) operate in the cell--to influence
      electrophysiology; (3) have a multicellular expression--e.g. mechanical
      distortion of one cell can raise intracellular calcium of an adjacent cell; (4)
      express in the intact organ--e.g. an increase in venous return hydraulically
      distends the sinoatrial node, steepening its pacemaker potential, thus increasing
      heart rate. It should also (5) demonstrate elements of a feedback system-
      "mechanoelectric feedback", and (6) interact with other systems--the cytoskeleton
      incorporates cell signalling complexes intersecting with other signal cascades.
      Finally, (7) it can malfunction to produce clinical abnormality--it contributes
      electrophysiologically to lethal cardiac arrhythmia. This anatomical and
      functional behaviour of mechanoelectric transduction could sanction the prospect
      of viewing it as analogous to the other integrative physiological systems.

PMID- 10070211
TI  - Modulation of ions channels and membrane receptors activities by mechanical
      interventions in cardiomyocytes: possible mechanisms for mechanosensitivity.

PMID- 10070212
TI  - The role of calcium in the response of cardiac muscle to stretch.
AB  - This review focuses on the complex interactions between two major regulators of
      cardiac function; Ca2+ and stretch. Initial consideration is given to the effect
      of stretch on myocardial contractility and details the rapid and slow increases
      in contractility. These are shown to be related to two diverse changes in Ca2+
      handling (enhanced myofilament Ca2+ sensitivity and increased intracellular Ca2+
      transient, respectively). Interaction between stretch and Ca2+ is also
      demonstrated with respect to the rhythm of cardiac contraction. Stretch has been
      shown to alter action potential configuration, generate stretch-activated
      arrhythmias, and increase the rate of beating of the sino-atrial node. A variety
      of Ca(2+)-dependent mechanisms including attenuation of Ca2+ extrusion via
      Na+/Ca2+ exchange, Ca2+ entry through stretch-activated channels (SACs) and
      mobilisation of intracellular Ca2+ stores have been proposed to account for the
      effect of stretch on rhythm. Finally, the interaction between stretch and Ca2+ in
      the secretion of natriuretic peptides and onset of hypertrophy is discussed.
      Evidence is presented that Ca2+ (entering through L-type Ca2+ channels or SACs,
      or released from sarcoplasmic reticular stores) influences secretion of both
      atrial and B-type natriuretic peptide; there is data to support both positive and
      negative modulation by Ca2+. Ca2+ also appears to be important in the pathway
      that leads to expression of precursors of hypertrophic protein synthesis. In
      conclusion, two of the major regulators of cardiac muscle function, Ca2+ and
      stretch, interact to produce effects on the heart; in general these effects
      appear to be additive.

PMID- 10070213
TI  - Stretch-induced changes in heart rate and rhythm: clinical observations,
      experiments and mathematical models.
AB  - Clinical and research data indicate that active and passive changes in the
      mechanical environment of the heart are capable of influencing both the
      initiation and the spread of cardiac excitation via pathways that are intrinsic
      to the heart. This direction of the cross-talk between cardiac electrical and
      mechanical activity is referred to as mechano-electric feedback (MEF). MEF is
      thought to be involved in the adjustment of heart rate to changes in mechanical
      load and would help to explain the precise beat-to-beat regulation of cardiac
      performance as it occurs even in the recently transplanted (and, thus,
      denervated) heart. Furthermore, there is clinical evidence that MEF may be
      involved in mechanical initiation of arrhythmias and fibrillation, as well as in
      the re-setting of disturbed heart rhythm by 'mechanical' first aid procedures.
      This review will outline the clinical relevance of cardiac MEF, describe cellular
      correlates to the responses observed in situ, and discuss the role that
      quantitative mathematical models may play in identifying the involvement of
      cardiac MEF in the regulation of heart rate and rhythm.

PMID- 10070214
TI  - Cardiac mechano-electric feedback in man: clinical relevance.
AB  - Clinical conditions associated with sudden cardiac death due to arrhythmia are
      frequently accompanied by abnormalities of mechanical loading and wall stretch.
      These arrhythmias may result from several mechanisms including secondary
      depolarisations during or following the action potential or from a combination of
      conduction slowing and action potential shortening. Mechanical perturbations have
      been shown to reproduce these electrophysiological effects experimentally.
      However the effect of mechanical intervention is complex depending on the timing
      and intensity of the stimulus and the interplay between effects mediated via
      stretch activated channels and calcium cycling. Studies in patients during
      cardiac catheterisation or cardiac surgery using monophasic action potentials
      have shown alteration in the time course and shape of action potential
      repolarisation in response to changes in ventricular loading. Although stretch in
      experimental preparations has been shown to be arrhythmogenic, particularly in
      pathological conditions, the role of mechanically induced electrophysiological
      changes in important clinical ventricular arrhythmias remains to be established.

PMID- 10070215
TI  - [Risk factors for coronary heart disease in university students aged 17 to 19].
AB  - OBJECTIVE: To study the prevalence of risk factors for coronary heart disease
      (CHD) in university students between 17 an 19 years of age. METHODS: A sample of
      289 first year students, 144 females and 145 males, of the University of Costa
      Rica were included for anthropometric, biochemical and physical studies. RESULTS:
      One in six (17% N = 48) had total cholesterol > 200 mg/dL and it was more
      frequent in females. High LDL-C > 130 mg/dL was found in 26% (N = 74) whereas low
      HDL-C was present in only 42% (N = 121). Nearly 10% (N = 28) smoked and 38% (N =
      111) did not exercise. Obesity was seen in 7% (N = 20) when the Body Mass Index
      was used as a criterium but only 1.4% (N = 4) by body fat. The distribution of
      risk factors was: one factor in 36% (N = 105), two factors in 27% (N = 77) and
      three or more in 13% (N = 37). The most common were sedentarism, dislipedemias
      and smoking. CONCLUSIONS: CHD risk factors were present in many of our
      adolescents. Our finding suggests the need to promote healthier lifestyles to
      minimize the potential of these factors to cause CHD in adulthood.

PMID- 10070216
TI  - [Five year experience with neonatal sepsis in a pediatric center].
AB  - OBJECTIVE: To describe the etiologic agents, clinical findings and hematologic
      changes associated to sepsis in patients admitted to the Neonatal Intensive Care
      Unit at the Hospital Infantil de Mexico Federico Gomez and to determine the
      frequency of normal CBC (Complete Blood Cell Count) at diagnosis of sepsis.
      METHODS: A chart review of septic patients hospitalized from January 1992 to
      December 1996 was done. RESULTS: 103 septic patients with 147 episodes of
      bacteremia were detected among 945 newborn admissions. The most common isolates
      in blood cultures were grampositive cocci (55%). Clinical findings associated to
      sepsis were non-specific. Premature infants presented apnea and jaundice more
      frequently than term infants (p < 0.05). At diagnosis of sepsis, 19% of premature
      infants had a normal CBC compared to 8% of term infants. Leukopenia was a poor
      prognosis-related finding, i.e. seven out of 35 patients who died were leukopenic
      vs 1 of 68 survivors (p < 0.05). Overall, mortality was 34%, but sepsis-related
      mortality was 13%. CONCLUSIONS: The incidence of sepsis in our population was
      high with grampositive cocci as the most common blood isolates. Clinical features
      associated to sepsis were non-specific. A significant proportion of septic
      preterm infants had normal CBC at diagnosis and leukopenia was a poor prognosis
      sign. Mortality associated to sepsis was high.

PMID- 10070217
TI  - [Evaluation of diagnostic tests for hypocalcemia in critically ill newborns].
AB  - OBJECTIVE: To determine sensitivity (Sn), specificity (Sp), positive and negative
      predictive values (PPV, NPV) of total and calculated calcium and of QTc and QoTc
      intervals for the diagnosis of hypocalcemia in critically ill newborns. SETTING:
      A neonatal intensive care unit. METHODS: We included all newborn less than 28
      days of age; we excluded those with calcium treatment, hypomagnesemia or
      congenital heart disease. Serum levels of total calcium, albumin and ionic
      calcium were measured as well as the QTc and QoTc intervals. Values for Sn, Sp,
      PPV and NPV were calculated according to cutoff points of the literature and with
      those of our receptor operating curves (ROC). Ionic calcium was considered the
      gold standard (hypocalcemia < 1.10 mmol/L). RESULTS: We included 53 newborns;
      21/53 (40%) had hypocalcemia. Clinical features were similar among patients with
      or without hypocalcemia. For total calcium the Sn was 47%; Sp = 87%; PPV = 71%
      and NPV = 72%. For calculated calcium there values were: 55, 75, 57 and 73; for
      QoTc: 47, 81, 61 and 70%; and for QTc: 19, 87, 50 and 62% respectively. With the
      ROC values the Sn for total calcium and QTc was improved. CONCLUSIONS: Among
      critical ill newborns, total and calculated calcium were better in identifying
      patients with hypocalcemia whereas QTc and QoTc were better in those without
      hypocalcemia.

PMID- 10070218
TI  - [Treatment of childhood acute lymphoblastic leukemia in a community hospital of
      the state of Veracruz].
AB  - OBJECTIVE: To describe the results of treatment of 36 consecutive children with
      acute lymphoblastic leukemia attending a second level community hospital in the
      Mexican State of Veracruz. CHARACTERISTICS OF THE CHILDREN: They were from
      families with very poor resources seen free of charge. Most (75%) were high risk
      cases. The most common high risk factors were an age outside the range of 2 to 9
      years (53%), a WBC count above 50 thousand/microL (36%) and an L-2 lymphocyte
      morphology (39%). RESULTS OF TREATMENT: Disease-free survival was 64% at 36
      months whereas event-free survival was 47% at 36 months which are low in
      comparison with the data in the literature. CONCLUSIONS: We believe we were able
      to obtain good results in the treatment of our leukemic cases which was not only
      a mostly high risk group but also had to contend with poor nutritional, cultural
      and socioeconomic conditions and with disease-related factors present in their
      communities.

PMID- 10070219
TI  - [Clinical-histopathological diagnostic agreement of lymph node biopsies in a
      tertiary care hospital].
AB  - OBJECTIVE: To determine the clinical-histopathologic concordancy in lymph node
      biopsies as well as the sensitivity and specificity of the clinical diagnoses in
      our institution. METHODS: We reviewed the files of patients with lymph node
      biopsy performed from January 1991 to July 1997. We estimated the clinical
      histopathologic concordancy with a kappa test. Our institution lacked the
      immunochemistry and ultrastructural techniques complementing the diagnoses.
      RESULTS: There were 72 biopsies. Most were from the cervical (N = 27), mesenteric
      (N = 13) or supraclavicular (N = 12) regions. The supraclavicular lymph nodes had
      the highest sensitivity for clinical diagnosis (S = 67%) and was mostly
      associated with neoplasias (lymphoma or metastatic cancer) in 75% of the cases.
      The global concordancy was fair (kappa 0.37) and the sensitivity and specificity
      of the clinical diagnoses were 50%. CONCLUSIONS: The concordancy as well as the
      clinical diagnostic sensitivity and specificity were low in our hospital. This
      justifies the efforts of continuing medical education in our institution to
      reduce errors in the diagnostic process.

PMID- 10070220
TI  - [Serum level of prostatic specific antigen in 100 patients with prostatic
      biopsy].
AB  - OBJECTIVE: To define the PSA levels (Prostatic Specific Antigen) in our patients
      with benign or malignant prostatic biopsy. METHODS: 100 patients with clinical
      suspicion of prostatic carcinoma (high levels of PSA and/or abnormal findings at
      digito-rectal examination) and who underwent a prostatic needle biopsy were
      reviewed. RESULTS: There were 66 benign and 34 carcinomas. The median PSA was
      11.2 ng/mL in the benign cases and 45.6 in cancer. In cases with small increases
      in PSA (49.9 ng/mL), 94% were benign; there was still a majority of benign cases
      (63%) in patients with a PSA of 10-29.9 ng/mL. Only in those with levels of 30+,
      malignancy was a majority (81%). CONCLUSIONS: There was a considerable overlap of
      PSA levels in our benign and malignant patients, and only values of 30+ ng/mL
      were highly suggestive of carcinoma. Our levels are higher than those informed in
      the literature and may have been due, at least partly, to the source of our
      reagent kits for PSA assays (Cedex from France and Diagnostic Products Corp from
      the U.S.).

PMID- 10070222
TI  - The diverse roles of citation indexes in scientific research.

PMID- 10070221
TI  - [Effects of bezafibrate in the diet of hypertensive patients with dyslipidemia
      and hyperfibrinogenemia].
AB  - OBJECTIVE: To evaluate the fibrinogen and lipids response to diet plus
      bezafibrate in insulin-resistant patients with arterial hypertension and mixed
      hyperlipidemia. METHODS: A randomized double blind parallel design was used
      during a 90 days treatment period. Fibrinogen, lipids, insulin and peptide C
      assays as well as a glucose tolerance test were done at the start and end of
      treatment. The 28 patients received a hypolipemic diet low in refined sugars with
      bezafibrate added (400 mg/day) in 15 and a placebo in 13. RESULTS: The groups
      were similar in age, blood pressure and BMI. At the end of treatment, fibrinogen,
      cholesterol, triglycerides and LDL-C were lower in both groups as compared to the
      initial values, but only in the bezafibrate group there were: a) significant
      decrease in triglycerides (64 mg/dL, p 0.01); and b) marginal changes in
      fibrinogen (decreased 35 mg/dL, p = 0.09), total cholesterol (decreased 26 mg/dL,
      p = 0.10) and glucose/insulin ratio (increased from 4.4 to 5.2, p = 0.09).
      Bezafibrate lowered slightly the insulin level but did not affect peptide C. A
      correlation of changes in fibrinogen levels and the 60 min insulin concentration
      in the glucose tolerance test was higher in the bezafibrate group (r = 0.61) than
      in the placebo group (r = 0.23). CONCLUSIONS: In insulin resistant patients with
      high cardiovascular risk, bezafibrate and a placebo added to a hypolipemic diet
      decreased plasma fibrinogen. Bezafibrate lowered significantly the levels of
      triglycerides in these patients.

PMID- 10070223
TI  - [The nosology of medical errors].

PMID- 10070224
TI  - [Clinical nutrition training in medical schools of Mexico].
AB  - OBJECTIVE: To describe the efforts carried out to strengthen nutrition education
      in Mexican medical schools. Emphasis was placed on the status previous to the
      program implementation, the design of a new basic curriculum, and the description
      of the main program strategies implemented. METHODS: a) Analysis of available
      medical curricula; b) Application of a questionnaire to the school deans; c)
      Assessment of knowledge of nutrition of advanced medical students; d) Design of a
      basic curriculum of clinical nutrition; e) Edition of a textbook; f) Design and
      implementation of program strategies to strengthen nutrition education. RESULTS:
      Clinical nutrition was not a topic included in most curricula analyzed and, when
      present, it was incorporated to related clinical subjects. Usually, emphasis was
      placed on basic topics of nutrition while clinical and applied subjects were
      considered less frequently. Lack of a specialized faculty and weakness of
      teaching infrastructure were some problems identified. A basic curriculum
      adaptable to different contexts was designed, and a textbook on clinical
      nutrition was edited and published. Training and formation of nutrition
      specialists were among the key programs implemented.

PMID- 10070225
TI  - [Cutaneous histoplasmosis in nine patients with AIDS].
AB  - In AIDS patients the diagnosis of systemic mycosis is a clinical challenge. When
      cutaneous affection occurs, the diagnosis is difficult because of the non
      specific clinical findings. We describe nine patients with AIDS and cutaneous
      histoplasmosis as the initial clinical manifestation. These patients were
      diagnosed from 1987 to 1998. In all the diagnosis of histoplasmosis was done by
      skin biopsy and fungal isolation. The main skin lesions were papules combined
      with pustules or nodules in 6 of 9 patients, ulcers (1/9), erythematous plaques
      (1/9) and nodules (1/9). Head and trunk were the main anatomical locations of the
      lesions. All had fever, 7/9 had liver and spleen enlargement and 5/9 had weight
      loss. At the time of diagnosis all patients had a low CD4+ lymphocyte counts with
      a mean of 47 cells/microL. Amphotericin B was the initial treatment followed by
      itraconazole. Five patients died, one day after diagnosis and four after 5, 8, 11
      and 12 months. Four are alive at 3, 3, 19 and 26 months of follow-up.
      CONCLUSIONS: In AIDS patients the skin involvement by histoplasmosis should
      always be included among the differential diagnoses specially in patients with
      face and trunk papules and fever and hepatosplenomegaly. Skin and bone marrow
      cultures were the most reliable diagnostic methods, but skin biopsy was the
      fastest procedure.

PMID- 10070226
TI  - [Fc gamma receptors in health and disease].
AB  - Receptors for the Fc fragment of immunoglobulins G (Fc gamma R) belong to the
      immunoglobulin superfamily and are expressed on different cell types. These
      receptors are classified in three different groups (Fc gamma RI, Fc gamma RII and
      Fc gamma RIII) depending upon their molecular weight, affinity and specificity
      for their ligands. In addition to all these differences, genetic polymorphisms
      induce the expression of several isoforms, making the Fc gamma R a heterogeneous
      group. The Fc gamma Rs have been the subject of intense research on their gene
      organization, biochemical and structural properties. It has also been established
      that the Fc gamma R play an important functional role on the regulation of the
      biological responses that are triggered during inflammatory stages (e.g. an
      infection), as they link the cellular and humoral branches of the immune
      response. In this article we give examples of the participation of Fc gamma R on
      the regulation of the immune response as well as the activation of intracellular
      mechanisms (transduction signals) after the crosslinking of Fc gamma R by antigen
      antibody complexes. The effect of cytokines and growth factors on the regulation
      of Fc gamma R expression is also described. We discuss the importance of the
      possible use of some of these molecules to control the expression of Fc gamma R
      in some clinical situations where alterations on their expression are associated
      with some diseases. Finally, we analyze the role of Fc gamma R as the point of
      entry of infectious agents such as HIV.

PMID- 10070227
TI  - [Mineral water and health].

PMID- 10070228
TI  - [Comparisons, the null hypothesis, apples and pears, disparities and nonsense].

PMID- 10070229
TI  - [Pharmacokinetics of beta blockers in hyperthyroidism. Therapeutic relevance].
AB  - Hyperthyroidism is associated with alterations in pharmacokinetic parameters such
      as absorption, distribution, metabolism and elimination. Beta-blockers are used
      in particular in the treatment of hyperthyroidism and are also subject to
      pharmacokinetic changes occurring during this pathology. The magnitude of these
      variations is examined when beta-blockers are used for clinical manifestations of
      hyperthyroidism or during thyroid surgery. Clinical means used to assess the
      accuracy of therapeutic drug monitoring are also described.

PMID- 10070230
TI  - [Is programmed ventricular stimulation still up to date in the medicinal
      evaluation of ventricular tachycardia?].
AB  - Despite considerable advances in the understanding of cardiac arrhythmia
      mechanisms, death in relation to ventricular tachyarrhythmias remains an
      important public health problem, and management of ventricular arrhythmias
      remains a perpetual challenge in clinical cardiology. In the last decade, the
      development and refinement of implantable cardioverter defibrillators and the
      progress in techniques of radiofrequency electrode catheter ablation and
      antiarrhythmic surgery have been revolutionary in the management of ventricular
      tachycardia. On the other hand, there have been major changes in the use of drug
      therapy since the publication of the results of the CAST study. Inclusion of
      mortality as an endpoint in clinical trials highlights the fact that some
      antiarrhythmic drugs may have the proclivity to exert fatal proarrhythmic
      reactions while also having the potential to control recurrences of ventricular
      tachycardia. All these changes that now need to be integrated into global
      approaches for ventricular arrhythmia control led us to wonder whether serial
      testing is still up to date in the management of ventricular tachycardia. After
      more than 20 years of clinical use, there is much concern about the use of serial
      drug testing to guide antiarrhythmic drug therapy for the management of life
      threatening sustained ventricular tachyarrhythmias in light of recent advances in
      the management of cardiac arrhythmias. The purpose of this article is to discuss,
      within a relatively brief compass, the cumulative data from different lines of
      investigations, results of randomized clinical trials, recently acquired beliefs
      and meta-analytic findings concerning the present place of serial
      electrophysiologic drug testing in the management of ventricular tachycardia.

PMID- 10070231
TI  - [Pharmacokinetic evaluation of a computerized target-controlled infusion system:
      application to propofol in orthopedic surgery].
AB  - PaMo 2.0, a type of software, includes a pharmacokinetic model for propofol in
      the adult. It allows both administration and monitoring of propofol target
      controlled infusions. In order to evaluate PaMo 2.0, a prospective clinical trial
      compared, at defined infusion times, predicted and measured plasma propofol
      concentrations, in 28 patients programmed for hip-replacement surgery. A propofol
      plasma determination technique had first been validated, including high
      performance liquid chromatography with fluorescence detection. A statistical
      analysis based on correlation (r = 0.73), inaccuracy = 29.18 per cent, bias =
      11.67 per cent, wobble = 19.15 per cent, and divergence = -0.06 per cent/min
      calculation, related to this system, has been carried out. PaMo 2.0 under
      estimated plasma propofol concentrations. The convergence between predicted and
      measured propofol concentrations was good and not modified in respect of infusion
      time. This infusion system is suitable for propofol administration, but the
      integration of Bayesian pharmacokinetic models would greatly improve propofol
      plasma concentration estimation and regimen adaptation to each patient.

PMID- 10070232
TI  - [Study of voluntary drug intoxication in an emergency unit].
AB  - Voluntary drug intoxications are not systematically recorded. Main aspects of
      this important problem have been studied in the unit responsible for medico
      psychological emergencies in the university hospital of Poitiers. Files of all
      patients admitted to the unit from January to December 1994 have been analysed
      and 598 patients were included in our study. Of these, 67 per cent were females.
      31 per cent were 20 to 29 years old and for the most part unemployed (62.5 per
      cent). Drugs most commonly used are benzodiazepines (39 per cent), alone or often
      associated with alcohol (33 per cent). A fatal outcome was observed in one
      patient. In many cases (50 per cent) this was not the first episode of voluntary
      intoxication; 53 per cent of the patients were discharged from hospital after a
      psychiatric consultation. For many years, voluntary drug intoxication frequency
      has increased continually. All cases have a specific intention that we have to
      clarify in order to take effective preventive measures to prevent recidivism.

PMID- 10070233
TI  - [Clinical research, evaluation of care and quality assurance].
AB  - This paper aims to clarify the concepts and terminology of clinical research,
      evaluation, and quality. Clinical research or clinical epidemiology aims to
      demonstrate the efficacy of medical care. The optimal methodology is a
      randomized, double-blind trial that allows a causal inference in respect of
      efficacy. This should be the first stage before generalization of all medical
      practice. Evaluation of quality of care aims to verify the effectiveness of
      medical care by comparing practice with references. The optimal methodology is
      clinical audit that allows fine-tuned diagnosis of the existence of deviant
      practices. The analysis of causes and correction of the care process are an
      integral part of the evaluation work. Thus quality assurance and quality
      management concepts and methods have been developed which tend to ensure
      solutions for better care and to maintain the level of quality of care to achieve
      patient satisfaction. Evaluation, clinical research and management quality could
      in fact be seen as the complementary facets of a comprehensive approach to
      quality of care.

PMID- 10070234
TI  - [Evaluation of the risk of venous thromboembolism in the medical patients].
AB  - The venous thromboembolic risk seems to be demonstrated in medical patients since
      the incidence of symptomatic and asymptomatic deep vein thrombosis (DVT) without
      any prophylactic methods is respectively about 50 per cent in stroke, 25 per cent
      in acute myocardial infarction (AMI) and 15 per cent in internal medicine. A
      synthesis of clinical trials performed in medical patients shows that
      prophylactic doses of heparins (unfractionated heparin or low molecular weight
      heparins) reduce the incidence of DVT by 40 to 60 per cent compared with the lack
      of any antithrombotic agents but without any significant effect on total
      mortality. Other antithrombotic agents such as antiplatelet agents seem to reduce
      the incidence of DVT by about 40 per cent associated with a significant decrease
      in total mortality of stroke or AMI. But the recommendations made on the basis of
      these results have to be extremely cautious since the number of medical patients
      included in clinical trials is quite limited compared with the surgical area.
      Moreover, each of these recommendations is not sufficiently proven. Thus more
      clinical trials have to be carried out with a placebo control group in internal
      medicine and an aspirin control group for stroke and AMI.

PMID- 10070235
TI  - [Synthesis: certainties/uncertainties in the prevention of venous thrombosis in
      medical patients].
AB  - In medical patients there are numerous and variable risk factors for deep vein
      thrombosis. Placebo-controlled clinical trials are rare. The efficacy of standard
      heparin or low molecular weight heparin for the prevention of deep vein
      thrombosis is clearly demonstrated for patients with recent myocardial
      infarction, ischaemic stroke with hemiplegia or severe pulmonary sepsis with lung
      failure. Pharmacological prophylaxis is probably also efficient in patients with
      a severe acute disease and a certain history of deep vein thrombosis. For all
      other medical and especially for bedridden elderly patients, use of low molecular
      weight heparin might decrease the incidence of deep vein thrombosis but might not
      modify the overall mortality. In these situations, placebo-controlled clinical
      trials are needed for best evaluation of the benefit-risk ratio.

PMID- 10070236
TI  - [Prevention of venous thrombosis: role of heparins].
AB  - Prevention of venous thromboembolism is of major importance because deep vein
      thrombosis is an economic burden. To prevent pulmonary embolism, whether fatal or
      not, and the postphlebitic syndrome, virtually all patients' level of risk should
      be assessed in order to provide adequate prophylactic measures against venous
      thromboembolism. Non-pharmacological, pharmacological or combined modalities can
      reduce the frequency of venous thrombosis. Evidence-based guidelines are
      available for most situations in surgical patients. However, in medical patients
      there are fewer data and there are wide variations of opinion. Systematic reviews
      should be performed and updated to obtain practice guidelines. Cost and
      effectiveness as well as patients' preferences should be taken into account.
      Randomized control trials are ongoing: low-molecular-weight heparins are being
      evaluated in general medical patients; other forms of prophylaxis or combined
      methods are also being investigated.

PMID- 10070237
TI  - [Prophylaxis of venous thromboembolism in medical patients: from medical decision
      tools to the use of low molecular weight heparin].
AB  - In France, low molecular weight heparins are largely used for prophylaxis of
      venous thromboembolic disease in medical patients. Although clinical trials show
      their efficacy in some particular clinical situations, there is no consensus
      about their use in non-surgical patients. A consequence is a wide disparity of
      prophylaxis of venous thromboembolic disease regimens: such a situation was
      observed during a practice survey in two medical units of the general hospital of
      Luneville. So, prior assessment for pharmacists and physicians was carried out to
      determine tools which guide decision-making. These comprise clinical practice
      guidelines, a record card which allows the scoring of risk for venous
      thromboembolic disease and a clinical algorithm leading to the appropriate
      prescription according to the risk and the haematological results. A second
      concomitant practice survey was organized in the same two units in order to
      measure the appropriateness of the decision-making tools in medical practice. The
      four-month study included 108 medical patients. The process was successful
      because: (1) validated practices are improved, particularly in respect of
      biological monitoring during treatment, and (2) the disparity of therapeutic
      strategies is highly reduced, the clinical practice guidelines being followed in
      81 per cent of all cases. Despite the lack of consensus, heightened awareness of
      the attendant risk in many medical conditions allows appropriate prophylactic
      measures to be taken. These measures need decision-making tools that are easy to
      use and that improve heparin prescribing and thus healthcare quality.

PMID- 10070238
TI  - [Evaluation of low molecular weight heparin prescription at the Centre
      Hospitalier Intercommunal de Creteil].
AB  - Low-molecular-weight heparin (LMWH) represents a great expense in general
      hospitals. At the Centre Hospitalier Intercommunal de Creteil (CHIC), the Quality
      Assessment Council had set up a study on the prescription of LMWH in order to
      assess concordance between prescriptions and local guidelines on the preventive
      uses of LMWH. Adherence to the consensus was found in 73 per cent of cases,
      overprescription in 10 per cent of cases and underprescription in 26 per cent of
      cases. It is planned to modify the local consensus, taking into account some
      clinical situations highlighted by this study, and to perform another evaluation
      in the near future.

PMID- 10070239
TI  - The prevention of venous thromboembolism: a statewide evaluation of practices in
      Massachusetts.
AB  - The objective of this study was to determine the proportion of Massachusetts
      Medicare patients who received prophylaxis for venous thromboembolism following
      colectomy, hysterectomy or total hip arthroplasty. The sample frame was all 90
      Massachusetts acute care hospitals, and the time frame was 1 April to 30
      September 1994. The patients discharged with an International Classification of
      Disease (ICD-9-CM) discharge diagnostic code (recorded in the Massachusetts
      Medicare Claims Database) for colectomy, hysterectomy or total hip arthroplasty
      were used to identify the target patient population. The sample population
      comprised 1397 patients randomly selected from the target population, including
      467 total hip arthroplasties, 474 colectomies, and 456 hysterectomies. Medical
      records were reviewed by trained nurse abstractors who collected information on
      the use of prophylaxis for venous thromboembolism. Prophylaxis for venous
      thromboembolism was employed by surgeons practicing in Massachusetts hospitals in
      93 per cent of total hip arthroplasty cases (regional variation 85-98 per cent),
      84 per cent of colectomies (regional variation 57-93 per cent), 66 per cent of
      hysterectomies (regional variation 35-71 per cent), and in 87 per cent of the
      subset of 111 hysterectomies with malignancy (regional variation 25-100 per
      cent). The results of this statewide study demonstrated significant regional and
      hospital-to-hospital variation in use of prophylaxis for venous thromboembolism
      following major surgery. A lower rate of prophylaxis use was observed in
      hospitals with fewer than 200 beds and in hospitals that did not have teaching
      programmes. Hospitals with below-average rates of prophylaxis were targeted for
      intensive quality improvement interventions.

PMID- 10070240
TI  - [Oxicam hypersensitivity syndrome].

PMID- 10070241
TI  - [Amnesic and criminal effect of benzodiazepines: case report with lorazepam].

PMID- 10070242
TI  - [Acute renal failure after massive voluntary intoxication with levodopa
      (MODOPAR)].

PMID- 10070243
TI  - [Hyponatremia and probable inappropriate secretion of antidiuretic hormone due to
      citalopram].

PMID- 10070244
TI  - [Benign acute pancreatitis probably due to taking ketoprofen].

PMID- 10070245
TI  - [Acute voluntary poisoning with meprobamate may still be fatal: case report].

PMID- 10070246
TI  - [Theophylline, myocardial infarction and hypertrophic obstructive
      cardiomyopathy].

PMID- 10070247
TI  - [Fatal encephalopathy induced by ceftazidime].

PMID- 10070248
TI  - Report of the Second Workshop on Age Adjustment.
AB  - This report contains a summary of the Second Workshop on Age Adjustment held at
      the National Center for Health Statistics on June 5-6, 1997. The workshop, which
      was a follow up to the First Workshop on Age Adjustment (1991), was held to
      consider changing the standard used for age-adjusting death rates and to develop
      an implementation plan. This report includes follow up to the recommendations
      from the first workshop. Participants in the second workshop included
      representatives from selected Federal agencies, State health departments,
      nongovernmental agencies, and academia. The participants recommended that the
      current population standard for age-adjusting death rates be changed from the
      1940 standard million population to a standard based on a projected year 2000
      population. On August 26, 1998, the Secretary, U.S. Department of Health and
      Human Services approved the recommendations of the second workshop as
      departmental policy effective with the 1999 data year. In addition, the proposed
      change has been widely publicized in presentations to State vital statistics
      programs and to Federal agencies.

PMID- 10070249
TI  - Control and surveillance of African trypanosomiasis. Report of a WHO Expert
      Committee.
AB  - Current estimates indicate that 60 million people are at risk of infection with
      human African trypanosomiasis or sleeping sickness, with about 300,000 new cases
      each year. However, less than 4 million people are under surveillance and only
      10% of new cases are diagnosed and treated. This report of a WHO Expert Committee
      reviews current epidemiological information on African trypanosomiasis and its
      vectors, and evaluates recent advances in drug treatment and the development of
      tools for the control and surveillance of the disease. The report provides
      examples of treatment schedules, vector control operations, indicators for
      monitoring control and surveillance activities and sample calculations for
      analysing the cost-effectiveness of different strategies, as well as details of
      methods for cryopreservation of trypanosome-infected blood samples and a
      description of traps and screens for the control of the insect vector, Glossina.
      Although primarily addressed to health policy-makers in countries endemic for
      sleeping sickness, this report will also be a useful reference source for health
      care staff at all levels, including physicians, nurses, auxiliary staff and
      students, as well as those engaged in research on the disease.

PMID- 10070250
TI  - Replication origins in metazoan chromosomes: fact or fiction?
AB  - The process by which eukaryotic cells decide when and where to initiate DNA
      replication has been illuminated in yeast, where specific DNA sequences
      (replication origins) bind a unique group of proteins (origin recognition
      complex) next to an easily unwound DNA sequence at which replication can begin.
      The origin recognition complex provides a platform on which additional proteins
      assemble to form a pre-replication complex that can be activated at S-phase by
      specific protein kinases. Remarkably, multicellular eukaryotes, such as frogs,
      flies, and mammals (metazoa), have counterparts to these yeast proteins that are
      required for DNA replication. Therefore, one might expect metazoan chromosomes to
      contain specific replication origins as well, a hypothesis that has long been
      controversial. In fact, recent results strongly support the view that DNA
      replication origins in metazoan chromosomes consist of one or more high frequency
      initiation sites and perhaps several low frequency ones that together can appear
      as a nonspecific initiation zone. Specific replication origins are established
      during G1-phase of each cell cycle by multiple parameters that include nuclear
      structure, chromatin structure, DNA sequence, and perhaps DNA modification. Such
      complexity endows metazoa with the flexibility to change both the number and
      locations of replication origins in response to the demands of animal
      development.

PMID- 10070251
TI  - Chemokines: extracellular messengers for all occasions?
AB  - Movement of leukocytes from peripheral blood into tissues, also called leukocyte
      extravasation, is absolutely essential for immunity in higher organisms. Over the
      past decade, our understanding of the molecular mechanisms involved in white
      blood cell extravasation during both normal immune surveillance and the
      generation of protective immune responses has taken a great leap forward with the
      discovery of the chemokine gene superfamily. Chemokines are low-molecular-weight
      cytokines whose major collective biological activity appears to be that of
      chemotaxis of both specific and overlapping subsets of leukocytes. They are
      therefore likely to play a critical role in the directed movement of leukocytes
      from the bloodstream into tissue. These molecules are almost exclusively secreted
      and act as extracellular messengers for the immune system. However, emerging data
      also show that various members of the chemokine gene superfamily exert other
      biological effects outside the immune system. All nucleated cells and all tissues
      examined to date are capable of expressing at least some chemokines, and it seems
      likely therefore that by the time all the chemokines are identified, and all
      their biological functions elucidated, we will find that, as a family, these
      molecules perform an extracellular messenger role in all tissues and systems of
      the body.

PMID- 10070252
TI  - Capacitative calcium entry channels.
AB  - In the phospholipase C signaling system, Ca(2+) is mobilized from intracellular
      stores by an action of inositol 1,4,5-trisphosphate. The depletion of
      intracellular calcium stores activates a calcium entry mechanism at the plasma
      membrane called capacitative calcium entry. The signal for activating the entry
      is unknown but likely involves either the generation or release, or both, from
      the endoplasmic reticulum of some diffusible signal. Recent research has focused
      on mammalian homologues of the Drosophila TRP protein as potential candidates for
      capacitative calcium entry channels. This review summarizes current knowledge
      about the nature of capacitative calcium entry signals, as well as the potential
      role of mammalian TRP proteins as capacitative calcium entry channel molecules.

PMID- 10070253
TI  - Negative regulation of the JAK/STAT pathway.
AB  - Cytokines induce a variety of biological responses by binding to specific cell
      surface receptors and activating cytoplasmic signal transduction pathways, such
      as the JAK/STAT pathway. Although these responses are generally transient, few
      molecules have been characterised that switch the signal off. Several different
      steps of the signal transduction pathway appear to be targeted by negative
      regulators, including the receptor/ligand complex, JAK kinases, and STAT
      transcription factors. Negative regulation is achieved by dephosphorylation of
      signalling intermediates by protein tyrosine phosphatases such as SHP-1, and by
      proteolytic degradation. Recent studies have identified two new families of
      negative regulatory molecules, SOCS and PIAS, which function in novel ways to
      suppress signal transduction pathways. The duration and intensity of a cell's
      response to cytokine therefore appear to be determined by the net effect of
      several regulatory mechanisms.

PMID- 10070254
TI  - Balanced regulation of microtubule dynamics during the cell cycle: a contemporary
      view.
AB  - Assembly of mitotic and meiotic spindles into an elliptical bipolar shape is an
      example of morphogenetic processes that involve local chromosomal regulation of
      microtubule dynamics for proper spatial microtubule assembly. Global microtubule
      dynamics during the cell cycle and local microtubule dynamics during spindle
      assembly are regulated by a balance between microtubule stabilizing and
      destabilizing factors. How a chromosome-induced phosphorylation gradient may be
      generated and modulate spindle microtubule assembly through balanced regulation
      of the activity of microtubule-associated proteins and Stathmin/Op 18 is
      analyzed.

PMID- 10070255
TI  - Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland
      development and neoplasia.
AB  - Growth and morphogenesis in the mammary gland depend on locally derived growth
      factors such as those in the epidermal growth factor (EGF) superfamily. Cripto-1
      (CR-1, human; Cr-1, mouse)--also known as teratocarcinoma-derived growth factor-1
      -is a novel EGF-related protein that induces branching morphogenesis in mammary
      epithelial cells both in vitro and in vivo and inhibits the expression of various
      milk proteins. In the mouse, Cr-1 is expressed in the growing terminal end buds
      in the virgin mouse mammary gland and expression increases during pregnancy and
      lactation. Cr-1/CR-1 is overexpressed in mouse and human mammary tumors and
      inappropriate overexpression of Cr-1 in mouse mammary epithelial cells can lead
      to the clonal expansion of ductal hyperplasias. Taken together, this evidence
      suggests that Cr-1/CR-1 performs a role in normal mammary gland development and
      that it might contribute to the early stages of mouse mammary tumorigenesis and
      the pathobiology of human breast cancer.

PMID- 10070256
TI  - Molecular clock mirages.
AB  - The hypothesis of the molecular clock proposes that molecular evolution occurs at
      rates that persist through time and across lineages, for a given gene. The
      neutral theory of molecular evolution predicts that the clock will be a Poisson
      process, with equal mean and variance. Experimental data have shown that the
      variance is typically larger than the mean. Hypotheses have been advanced to
      account for the hypervariance of molecular evolution. Four recent papers show
      that none of the predictive hypotheses that have been proposed can be generally
      maintained. The conclusion is that molecular evolution is dependent on the fickle
      process of natural selection. But it is a time-dependent process, so that
      accumulation of empirical data often yields an approximate clock, as a
      consequence of the expected convergence of large numbers.

PMID- 10070257
TI  - Construction of mammalian artificial chromosomes: prospects for defining an
      optimal centromere.
AB  - Two reports have shown that mammalian artificial chromosomes (MAC) can be
      constructed from cloned human centromere DNA and telomere repeats, proving the
      principle that chromosomes can form from naked DNA molecules transfected into
      human cells. The MACs were mitotically stable, low copy number and bound
      antibodies associated with active centromeres. As a step toward second-generation
      MACs, yeast and bacterial cloning systems will have to be adapted to achieve
      large MAC constructs having a centromere, two telomeres, and genomic copies of
      mammalian genes. Available construction techniques are discussed along with a new
      P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined
      to other PACs in vitro, avoiding a cloning step during which large repetitive
      arrays often rearrange. The PAC system can be used as a route to further define
      the optimal DNA elements required for efficient MAC formation, to investigate the
      expression of genes on MACs, and possibly to develop efficient MAC-delivery
      protocols.

PMID- 10070258
TI  - The evolution of a mechanism of cell suicide.
AB  - In the vertebrates, programmed cell death or apoptosis frequently involves the
      relocalization of mitochondrial cytochrome c to the cytoplasm. This prominent
      role in the regulation of apoptosis is in addition to the primary function of
      cytochrome c in the mitochondrial electron transport chain. These seemingly
      divergent roles become plausible when considering the symbiotic origin of the
      mitochondrion. Symbiosis involves conflicts between levels of selection, in this
      case between the primitive host cell and the protomitochondria. In an aerobic
      environment, selection on the protomitochondria may have favored routine
      manipulations of the host cell's phenotype using products and by-products of
      oxidative phosphorylation, in particular reactive oxygen species (ROS). Blocking
      the mitochondrial electron transport chain by removing cytochrome c enhances the
      production of ROS; thus cytochrome c release by protomitochondria may have
      altered the host cell's phenotype via enhanced ROS production. Subsequently, this
      signaling pathway may have been refined by selection so that cytochrome c itself
      became the trigger for changes in the host's phenotype. A mechanism of apoptosis
      in metazoans may thus be a vestige of evolutionary conflicts within the
      eukaryotic cell.

PMID- 10070259
TI  - Isolation and physical characterization of an exocellular polysaccharide.
AB  - The physical properties of a polysaccharide produced by the lactic acid bacterium
      Lactococcus lactis subsp. cremoris strain NIZO B40 were investigated. Separation
      of the polysaccharide from most low molar mass compounds in the culture broth was
      performed by filtration processes. Residual proteins and peptides were removed by
      washing with a mixture of formic acid, ethanol, and water. Gel permeation
      chromatography (GPC) was used to size fractionate the polysaccharide. Fractions
      were analyzed by multiangle static light scattering in aqueous 0.10 M NaNO3
      solutions from which a number- (Mn) and weight-averaged (Mw) molar mass of (1.47
      +/- 0.06).10(3) and (1.62 +/- 0.07).10(3) kg/mol, respectively, were calculated
      so that Mw/Mn approximately 1.13. The number-averaged radius of gyration was
      found to be 86 +/- 2 nm. From dynamic light scattering an apparent z-averaged
      diffusion coefficient was obtained. Upon correcting for the contributions from
      intramolecular modes by extrapolating to zero wave vector a hydrodynamic radius
      of 86 +/- 4 nm was calculated. Theoretical models for random coil polymers show
      that this z-averaged hydrodynamic radius is consistent with the z-averaged radius
      of gyration, 97 +/- 3 nm, as found with GPC.

PMID- 10070260
TI  - Association behavior of native beta-lactoglobulin.
AB  - The association behavior of beta-lactoglobulin has been studied by small-angle
      neutron scattering as a function of protein concentration, temperature, pH, and
      NaCl concentration of the solution. By indirect Fourier transformation of the
      spectra, pair-distance distribution functions for the various samples were
      obtained. These functions provided information on the maximum size, the weight
      averaged molecular mass, and the z-averaged radius of gyration of the beta
      lactoglobulin particles. At room temperature and pH values below 4 and above 5.2
      the protein consists predominantly of monomers and dimers, consistent with
      literature. In these pH regimes the formation of dimers is favored upon
      increasing ionic strength and decreasing protein charge (pH values closer to the
      isoelectric point of the protein). Around pH 4.7, larger oligomeric structures
      are formed, enhanced by a decrease in temperature and a decrease in ionic
      strength. beta-Lactoglobulin A associates more strongly than beta-lactoglobulin
      B. Surprisingly, at pH 6.9 larger structures than dimers seem to be formed at
      high protein concentrations (> 30 mg mL-1).

PMID- 10070261
TI  - Conformational analysis of peptide fragments derived from the peripheral subunit
      binding domain from the pyruvate dehydrogenase multienzyme complex of Bacillus
      stearothermophilus: evidence for nonrandom structure in the unfolded state.
AB  - There is currently a great deal of interest in the early events in protein
      folding. Two issues that have generated particular interest are the nature of the
      unfolded state under native conditions and the role of local interactions in
      folding. Here, we report the results of a study of a set of peptides derived from
      a small two-helix protein, the peripheral subunit-binding domain of the pyruvate
      dehydrogenase multienzyme complex. Five peptides of overlapping sequence were
      prepared, including sequences corresponding to each of the helices and to the
      region connecting them. The peptides were characterized by CD and, where
      possible, nmr. A peptide corresponding to the second helix is between 12 and 17%
      helical at neutral pH. CD also indicates a lower percentage of helical structure
      in the peptide corresponding to the first alpha-helix, although the values of the
      alpha-proton chemical shifts suggest some preference for nonrandom structure.
      Peptides corresponding to the interhelical loop, which in the full domain
      contains two overlapping beta-turns and a 5-residue 3(10)-helix, are less
      structured. There is no significant change in the helicity of any of these
      peptides with pH. To test for fragment complementation, CD spectra of the two
      peptides derived from each helix and the long connecting peptide were compared to
      the spectra of each possible pair, as well as to a mixture containing all three.
      No increase in structure was observed. We complement our peptide studies by
      characterizing a point mutant, D34V, which disrupts a critical hydrogen bonding
      network. This mutant is unable to fold and provides a useful model of the
      denatured state. The mutant is between 9 and 16% helical as judged by CD. The
      modest amount of helical structure formed in some of the peptide fragments and in
      the point mutant suggests that the denatured state of the peripheral subunit
      binding domain is not completely unstructured. This may contribute to the very
      rapid folding observed for the intact protein.

PMID- 10070262
TI  - NMR studies of the structure and dynamics of peptide E, an endogenous opioid
      peptide that binds with high affinity to multiple opioid receptor subtypes.
AB  - Structural and dynamic properties of opioid peptide E have been examined in an
      sodium dodecyl sulfate (SDS) micelle. Structural and dynamic studies both
      indicate that this peptide exhibits greater segmental mobility than typical
      structured proteins. An nmr structural analysis of adrenal peptide E in SDS
      micelles indicated the presence of two well-defined beta-turns, one at the N
      terminus encompassing residues 3 to 6, and the second in the region between
      residues 15 and 18. Certain side chain dihedral angles were also remarkably well
      defined, such as the chi 1 angle of F4, which exhibited a trans configuration.
      These calculated structures were based on a set of 9.5 restraints per residue.
      The backbone dynamics of peptide E in SDS micelles were examined through an
      analysis of 15N-relaxation parameters. An extended model-free analysis was used
      to interpret the relaxation data. The overall rotational correlation time is 19.7
      ns. the average order parameter S2 is 0.66 +/- 0.15. The N-terminal loop region
      residues including G3 to R6 have an average order parameter of 0.70 +/- 0.23. The
      average order parameter lies somewhere between that observed for a random coil
      (e.g., S2 = 0.3) and that of a well-defined tertiary fold (e.g., S2 = 0.86). This
      suggests that peptide E in SDS micelles adopts a restricted range of
      conformations rather than a random coil. Based on the helical structure recently
      obtained for the highly homologous kappa-agonist dynorphin-A(1-17) and the beta
      turn in the same region of peptide E, it is reasonable to assume that these two
      elements of secondary structure reflect different receptor subtype binding
      geometries. The intermediate order parameters observed for peptide E in an SDS
      micelle suggest a degree of dynamic mobility that may enable facile
      interconversion between helical and beta-turn geometries in the N-terminal
      agonist domain.

PMID- 10070263
TI  - Comparison of the dynamics of bovine and human angiogenin: a molecular dynamics
      study.
AB  - Molecular dynamics simulations have been carried out for 1 ns on human and bovine
      angiogenin systems in an effort to compare and contrast their dynamics. An
      analysis of their dynamics is done by examining the rms deviations, following
      hydrogen-bonding interactions and looking at the role of water in and around the
      protein. The C-terminus of bovine angiogenin moves appreciably during dynamics
      suggesting a better structure for ligand binding. However, we do not find any
      evidence of a conformation where the glutamate residue that obstructs the active
      site takes on a different conformation. We observe a differential hydrogen
      bonding pattern in the active site regions of bovine and human angiogenins, which
      could have a bearing on the different catalytic activities of the proteins. We
      also propose that the differential binding of the monoclonal antibody toward the
      two proteins might be due sequential and not conformational differences. Water
      molecules might play an important functional role in both proteins given their
      subtle functional differences. A simple computation on the molecular dynamics
      data has been carried out to identify locations in and around the protein that
      are invariably occupied by water. The locations of nearly half the waters we have
      identified from the simulation as being invariant in bovine angiogenin occupy
      similar locations in the bovine angiogenin crystal structure. The positions of
      the waters identified in human angiogenin differ considerably from that of bovine
      angiogenin.

PMID- 10070264
TI  - Complete suboptimal folding of RNA and the stability of secondary structures.
AB  - An algorithm is presented for generating rigorously all suboptimal secondary
      structures between the minimum free energy and an arbitrary upper limit. The
      algorithm is particularly fast in the vicinity of the minimum free energy. This
      enables the efficient approximation of statistical quantities, such as the
      partition function or measures for structural diversity. The density of states at
      low energies and its associated structures are crucial in assessing from a
      thermodynamic point of view how well-defined the ground state is. We demonstrate
      this by exploring the role of base modification in tRNA secondary structures,
      both at the level of individual sequences from Escherichia coli and by comparing
      artificially generated ensembles of modified and unmodified sequences with the
      same tRNA structure. The two major conclusions are that (1) base modification
      considerably sharpens the definition of the ground state structure by
      constraining energetically adjacent structures to be similar to the ground state,
      and (2) sequences whose ground state structure is thermodynamically well defined
      show a significant tendency to buffer single point mutations. This can have
      evolutionary implications, since selection pressure to improve the definition of
      ground states with biological function may result in increased neutrality.

PMID- 10070265
TI  - Computational investigations of structural changes resulting from point mutations
      in a collagen-like peptide.
AB  - The results of 0.5-1.0 ns molecular dynamics simulations of the collagen-like
      peptides [(POG)4(POA)(POG)4]3 and [(POG)9]3 (POG: proline-hydroxyproline-glycine)
      are presented. All simulations were performed using the AMBER-94 molecular
      mechanical force field with a shell of TIP3P waters surrounding the peptides. The
      initial geometries for the collagen-like peptides included an x-ray
      crystallographic structure, a computer-generated structure, a [(POG)9]3 structure
      modeled from the x-ray structure, and the x-ray structure with crystallographic
      waters replaced with a shell of modeled TIP3P waters. We examined the molecular
      dynamics peptide residue rms deviation fluctuations, dihedral angles, molecular
      and chain end-to-end distances, helical parameters, and peptide-peptide and
      peptide-solvent hydrogen-bonding patterns. Our molecular dynamics simulations of
      [(POG)4(POA)(POG)4]3 show average structures and internal coordinates similar to
      the x-ray crystallographic structure. Our results demonstrate that molecular
      dynamics can be used to reproduce the experimental structures of collagen-like
      peptides. We have demonstrated the feasibility of using the AMBER-94 molecular
      mechanical force field, which was parameterized to model nucleic acids and
      globular proteins, for fibril proteins. We provide a new interpretation of
      peptide-solvent hydrogen bonding and a peptide-peptide hydrogen bonding pattern
      not previously reported in x-ray studies. Last, we report on the differences; in
      particular with respect to main-chain dihedral angles and hydrogen bonding,
      between the native and mutant collagen-like peptides.

PMID- 10070266
TI  - Binding of proteins to copolymers of varying hydrophobicity.
AB  - Hydrophobic interactions between proteins and amphiphilic polyelectrolytes were
      studied by frontal analysis continuous capillary electrophoresis (Gao et al.,
      Analytical Chemistry, 1997, Vol. 69, pp. 2945-2951). Binding isotherms were
      obtained for beta-lactoglobulin and for bovine serum albumin interacting with a
      series of alternating copolymers of maleic acid and alkyl-vinyl ethers of varying
      hydrophobicity. Although binding between proteins and copolymers increases with
      increasing alkyl chain length, a minimum alkyl chain length of 3-4 methylenes is
      required for significant hydrophobic interactions to occur. These copolymers,
      like other polyamphiphiles, can form intrapolymer micelles, and the extent of
      such micellization decreases with increasing degree of carboxylate ionization.
      Binding results obtained at different pHs suggest that competition exists between
      intrapolymer micelle formation and protein-polymer hydrophobic interactions.

PMID- 10070267
TI  - Mixed cryoglobulinaemia after hepatitis C virus: more and less ambiguity.

PMID- 10070268
TI  - Influence of hypoxia in inflammatory synovitis.

PMID- 10070269
TI  - A man with intermittent fever and arthralgia.

PMID- 10070270
TI  - Prevalence of generalised osteoarthritis in patients with advanced hip and knee
      osteoarthritis: the Ulm Osteoarthritis Study.
AB  - OBJECTIVES: Different prevalences of generalised osteoarthritis (GOA) in patients
      with knee and hip OA have been reported. The aim of this investigation was to
      evaluate radiographic and clinical patterns of disease in a hospital based
      population of patient subgroups with advanced hip and knee OA and to compare the
      prevalence of GOA in patients with hip or knee OA, taking potential confounding
      factors into account. METHODS: 420 patients with hip OA and 389 patients with
      knee OA scheduled for unilateral total joint replacement in four hospitals
      underwent radiographic analysis of ipsilateral and contralateral hip or knee
      joint and both hands in addition to a standardised interview and clinical
      examination. According to the severity of radiographic changes in the
      contralateral joints (using Kellgren-Lawrence > or = grade 2 as case definition)
      participants were classified as having either unilateral or bilateral OA. If
      radiographic changes of two joint groups of the hands (first carpometacarpal
      joint and proximal/distal interphalangeal joints defined as two separate joint
      groups) were present, patients were categorised as having GOA. RESULTS: Patients
      with hip OA were younger (mean age 60.4 years) and less likely to be female
      (52.4%) than patients with knee OA (66.3 years and 72.5% respectively). Intensity
      of pain and functional impairment at hospital admission was similar in both
      groups, while patients with knee OA had a longer symptom duration (median 10
      years) compared with patients with hip OA (5 years). In 41.7% of patients with
      hip OA and 33.4% of patients with knee OA an underlying pathological condition
      could be observed in the replaced joint, which allowed a classification as
      secondary OA. Some 82.1% of patients with hip and 87.4% of patients with knee OA
      had radiographic changes in their contralateral joints (bilateral disease). The
      prevalence of GOA increased with age and was higher in female patients. GOA was
      observed more often in patients with knee OA than in patients with hip OA (34.9%
      versus 19.3%; OR = 2.24; 95% CI: 1.56, 3.21). Adjustment for the different age
      and sex distribution in both patient groups, however, takes away most of the
      difference (OR = 1.32; 95% CI: 0.89, 1.96). CONCLUSION: The crude results confirm
      previous reports as well as the clinical impression of GOA being more prevalent
      in patients with advanced knee OA than in patients with advanced hip OA. However,
      these different patterns might be attributed to a large part to a different
      distribution of age and sex in these hospital based populations.

PMID- 10070271
TI  - Cyclical etidronate increases bone density in the spine and hip of postmenopausal
      women receiving long term corticosteroid treatment. A double blind, randomised
      placebo controlled study.
AB  - OBJECTIVE: To study the effect of cyclic etidronate in secondary prevention of
      corticosteroid induced osteoporosis. METHODS: A double blind, randomised placebo
      controlled study comparing cyclic etidronate and placebo during two years in 37
      postmenopausal women receiving long term corticosteroid treatment, mainly for
      polymyalgia rheumatica (40% of the patients) and rheumatoid arthritis (30%). Bone
      density was measured in the lumbar spine, femoral neck, and femoral trochanter.
      RESULTS: After two years of treatment there was a significant difference between
      the groups in mean per cent change from baseline in bone density in the spine in
      favour of etidronate (p = 0.003). The estimated treatment difference (mean (SD))
      was 9.3 (2.1)%. Etidronate increased bone density in the spine (4.9 (2.1)%, p <
      0.05) whereas the placebo group lost bone (-2.4 (1.6)%). At the femoral neck
      there was an estimated difference of 5.3 (2.6)% between the groups (etidronate:
      3.6% (1.4)%, p < 0.05, placebo: -2.4 (2.1)%). The estimated difference at the
      trochanter was 8.2 (3.0) (etidronate: 9.0 (1.5)%, p < 0.0001, placebo: 0.5
      (2.3)%). No significant bone loss occurred in the hip in placebo treated
      patients. CONCLUSIONS: Cyclic etidronate is an effective treatment for
      postmenopausal women receiving corticosteroid treatment and is well tolerated.

PMID- 10070272
TI  - Cryoglobulinaemia and rheumatic manifestations in patients with hepatitis C virus
      infection.
AB  - OBJECTIVES: To investigate the association of cryoglobulinaemia and rheumatic
      manifestations in Korean patients with hepatitis C virus (HCV) infection.
      METHODS: Forty nine Korean patients with HCV infection were recruited. The
      prevalence, concentration, and type of cryoglobulin (by immunofixation),
      rheumatoid factor (RF), antinuclear antibody (ANA), and various rheumatological
      symptoms were investigated and HCV genotype was determined by polymerase chain
      reaction with genotype specific primer. RESULTS: The prevalence of cryoglobulin
      was 59% in Korean HCV patients and the concentration of cryoglobulin was 9.8
      (7.9) g/l (mean (SD)). The type of cryoglobulinaemia was identified in 23 (80%)
      of 29 HCV patients with cryoglobulinaemia and they were all type III. There were
      no differences in age, sex, history of operation and transfusion, proportion of
      liver cirrhosis between the patients with cryoglobulinaemia and those without
      cryoglobulinaemia. The frequencies of RF and ANA were 14% and 3.4% respectively
      in HCV patients with cryoglobulinaemia. There was no difference in HCV genotype
      between the patients with cryoglobulinaemia and those without cryoglobulinaemia.
      Clinical features of HCV patients were as follows: arthralgia/arthritis (35%),
      cutaneous manifestation (37%), Raynaud's phenomenon (8%), paresthesia (44%), dry
      eyes (22%), dry mouth (10%), oral ulcer (33%), and abdominal pain (14%). However,
      these rheumatological symptoms did not differ between the two groups. CONCLUSION:
      Although the rheumatological symptoms were not different between HCV patients
      with and without cryoglobulinaemia, HCV patients showed various rheumatological
      manifestations. These result suggests that HCV infection could be included as one
      of the causes in patients with unexplained rheumatological symptoms.

PMID- 10070273
TI  - Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release
      from peripheral blood monocytes after intra-articular glucocorticoid treatment.
AB  - OBJECTIVES: A generalised transient improvement may follow intra-articular
      administration of glucocorticoids to patients with inflammatory arthropathy. This
      may represent a systemic anti-inflammatory effect of glucocorticoid released from
      the joint, mediated through processes such as altered leucocyte trafficking or
      suppressed release of pro-inflammatory cytokines. Patients, who had received
      intra-articular injections of glucocorticoids were therefore studied for evidence
      of these two systemic effects. METHODS: Patients with rheumatoid arthritis were
      studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF
      alpha) release by peripheral blood monocytes, blood cortisol concentrations, and
      blood methylprednisolone concentration were measured for 96 hours after intra
      articular injection of methylprednisolone acetate. RESULTS: Measurable
      concentrations of methylprednisolone were present in blood for up to 96 hours
      after injection. Significant suppression of the hypothalamic-pituitary-adrenal
      axis persisted throughout this time. Altered monocyte and lymphocyte trafficking,
      as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by
      four hours after injection and resolved in concordance with the elimination of
      methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of
      TNF alpha by endotoxin stimulated peripheral blood monocytes was suppressed at
      four hours and thereafter. Suppression was maximal at eight hours and was largely
      reversed by the glucocorticoid antagonist, mifepristone. CONCLUSIONS: After intra
      articular injection of methylprednisolone, blood concentrations of glucocorticoid
      are sufficient to suppress monocyte TNF alpha release for at least four days and
      to transiently alter leucocyte trafficking. These effects help to explain the
      transient systemic response to intra-articular glucocorticoids. Suppression of
      TNF alpha is principally a direct glucocorticoid effect, rather than a
      consequence of other methylprednisolone induced changes to blood composition.

PMID- 10070274
TI  - Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases:
      a preliminary report.
AB  - OBJECTIVE: The NF-kappa B/Rel family of transcription factors regulates the
      expression of many genes involved in the immune or inflammatory response at the
      transcriptional level. The aim of this study was to determine whether distinctive
      patterns of NF-kappa B activation are seen in different forms of joint disease.
      METHODS: The DNA binding activity of these nucleoproteins was examined in
      purified synovial and peripheral T cells from patients with various chronic
      rheumatic diseases (12: four with rheumatoid arthritis; five with
      spondyloarthropathies; and three with osteoarthritis). RESULTS: Electrophoretic
      mobility shift assays disclosed two specific complexes bound to a NF-kappa B
      specific 32P-labelled oligonucleotide in nucleoproteins extracted from purified T
      cells isolated from synovial fluid and peripheral blood of patients with
      rheumatoid arthritis. The complexes consisted of p50/p50 homodimers and p50/p65
      heterodimers. Increased NF-kappa B binding to DNA in synovial T cells was
      observed relative to peripheral T cells. In non-rheumatoid arthritis, binding of
      NF-kappa B in synovial T cells was exclusively mediated by p50/p50 homodimers.
      CONCLUSION: Overall, the results suggest that NF-kappa B may play a central part
      in the activation of infiltrating T cells in chronic rheumatoid arthritis. The
      activation of this nuclear factor is qualitatively different in rheumatoid
      synovial T cells to that in other forms of non-rheumatoid arthritis (for example,
      osteoarthritis, spondyloarthropathies).

PMID- 10070275
TI  - Down regulation by iron of prostaglandin E2 production by human synovial
      fibroblasts.
AB  - OBJECTIVE: To examine the effect of iron on the prostaglandin (PG) E2 production
      by human synovial fibroblasts in vitro. METHODS: Human synovial fibroblasts were
      isolated from synovial tissue of rheumatoid arthritis (RA) and osteoarthritis
      (OA) patients and cultured in medium. Synovial fibroblasts were stimulated by
      human recombinant interleukin (IL) 1 beta (0.1-10 ng/ml) with or without ferric
      citrate (Fe-citrate, 0.01-1 mM). The amount of PGE2 in the culture medium was
      measured by an enzyme linked immunosorbent assay. RESULTS: The production of PGE2
      by the synovial fibroblasts was increased by stimulation with IL1 beta at all
      concentrations tested. Fe-citrate but not sodium citrate (Na-citrate) down
      regulated the production of PGE2 by the synovial fibroblasts, both with and
      without stimulation by IL1 beta. Fe-citrate inhibited the spontaneous PGE2
      production by the cells in a dose dependent manner, and a maximum inhibition by
      Fe-citrate was observed at the concentration of 0.1 mM with IL1 beta stimulation.
      The down regulation by iron was reversed by the co-addition of desferrioxamine
      (100 micrograms/ml), an iron chelator. CONCLUSION: Iron down regulates the PGE2
      production by synovial fibroblasts in vitro.

PMID- 10070276
TI  - Radiological changes of short and flat bones in primary hypertrophic
      osteoarthropathy.

PMID- 10070277
TI  - Chondrocalcinosis and Gitelman's syndrome. A new association?

PMID- 10070278
TI  - Parotid lipomatosis in HIV positive patients: a new clinical disorder associated
      with protease inhibitors.

PMID- 10070279
TI  - Ultrasound guided injection of plantar fasciitis.

PMID- 10070280
TI  - Introduction: the EUROCARE II Study.
AB  - This introduction provides a general overview of the aims, methods and procedures
      used in the EUROCARE II study and the types of analyses presented in each article
      of this Special Issue of the European Journal of Cancer. The main aims of the
      EUROCARE II project are the updating of the survival database of the European
      Cancer Registries, the study of recent trends in relative survival rates and the
      interpretation of the survival differences observed both in time and across
      populations. Once having completed the preliminary stage of data checking, a
      total of 3,473,659 individual records from patients of all cancer sites,
      diagnosed between 1978 and 1989 and provided by 45 cancer registries in 17
      European countries were accepted to build up the EUROCARE database. The quality
      of these data, in terms of the accuracy of the diagnosis and the validity of
      vital status assessment, was checked by indirect indicators, based on cross
      validation analysis of consistency of the relevant variables. Statistical
      analysis was based on age-specific relative survival rates, computed for each
      cancer sites as the ratio of observed survival to the expected survival of the
      general population of the same area, gender and age, according to the Hakulinen
      method. An estimate of the European survival was computed as a weighted mean of
      the corresponding survival of the different countries, using as weights the
      expected yearly number of incident cases in each country. For comparison
      purposes, age-standardised survival was also calculated for Europe and for each
      country involved in the study.

PMID- 10070281
TI  - Variation in survival of patients with head and neck cancer in Europe by the site
      of origin of the tumours. EUROCARE Working Group.
AB  - The study describes the prognosis of head and neck cancer in Europe on the basis
      of information available to population-based cancer registries collaborating in
      the EUROCARE II project. Variation in survival in relation to country and the
      anatomical site/sub-site of origin of the tumours was examined. Survival analysis
      was carried out on 35,004 head and neck cancer cases (ICD 141, 143-148 and 161)
      diagnosed between 1985 and 1989 in 17 European countries. Prognosis varied
      considerably according to anatomical site: the best 5-year survival rates were
      seen for cancer of the larynx (63% in men) and the worst for cancer of the
      hypopharynx (22% in men). Five-year relative survival of male patients with
      cancer of the tongue, mouth and pharynx (ICD 141, 143-148) was 34% and ranged
      from over 45% in Iceland, Sweden, The Netherlands and Austria to less than 25% in
      Eastern European countries. Survival for larynx cancer ranged from over 70% in
      Iceland, Sweden, The Netherlands and Germany to less than 50% in Slovakia, Poland
      and Estonia. Apparently, France had the lowest survival (relative risk (RR) of
      dying versus Finland = 1.29) in Western Europe; after adjustment for ICD 3-digit
      anatomical sites the difference disappeared (RR = 1.04). Eastern European
      countries remained at the bottom of the survival range (RR > 1.4). The analyses
      adjusting by sub-site (ICD fourth digit) were confined to registries for which
      the proportion of unspecified sub-sites was less than 20%. Geographical
      differences in survival between Western European countries were largely due to a
      difference in case mix of anatomical sub-sites. However, after correcting for
      different sub-site distribution, differences persisted between Eastern and
      Western European countries. This is likely to be due to late diagnosis and to
      late referral or poor access of patients to adequately equipped treatment
      centres.

PMID- 10070282
TI  - Variation in survival for adults with nasopharyngeal cancer in Europe, 1978-1989.
      EUROCARE Working Group.
AB  - During the period 1978-1989, 2,054 new patients with nasopharyngeal carcinoma
      (NPC) were registered in the EUROCARE study, which, during 1985-1989 involved 45
      population-based cancer registries in 17 countries. The follow-up time was at
      least 5 years. 48% of all cases were squamous cell carcinomas and 39%
      undifferentiated carcinomas, which were more frequent in males. The overall
      relative 1- and 5-year survival rates (data included from 8 countries with
      complete data) were 75 and 34%, respectively, for males, and 72 and 32%,
      respectively, for females, but in a multivariate analysis, there was no
      significant difference in risk between males and females (0.93 (0.84-1.01),
      hazard ratio (HR) with 95% confidence interval (95% CI) for females). The overall
      relative 5-year survival (data included from nine countries with complete data)
      declined with age, from 53% for patients aged 15-44 years to 31% for patients
      aged 65-74 years. For patients with undifferentiated tumours, higher survival
      rates were observed in Scandinavia, Slovakia and Mediterranean countries, with
      lower rates for patients from the U.K. and Estonia. Survival for patients with
      squamous cell carcinoma was lowest in Scotland, England and Estonia. In a
      multivariate analysis, there was a significant difference in risk of death
      between those with squamous cell carcinomas and those with undifferentiated (HR
      0.82, 95% CI 0.74-0.90). Between 1978 and 1989, the prognosis did not change.

PMID- 10070283
TI  - Survival of patients with oesophageal and gastric cancers in Europe. EUROCARE
      Working Group.
AB  - The EUROCARE study is a European Union project to collect survival data from
      population-based cancer registries and analyse them according to standardised
      procedures. We investigated and compared oesophageal and gastric cancer survival
      in 17 countries between 1985 and 1989. Time trends in survival over the 1978-1989
      period were also investigated in 13 countries. The overall European 1-year
      relative survival rates were 33% for oesophageal cancer and 40% for gastric
      cancer. The corresponding 5-year relative survival rates were 10 and 21%,
      respectively. Important intercountry survival differences exist within Europe for
      oesophageal and gastric cancer. Taking the European average as the reference, the
      relative risk (RR) of death at 5 years was at least 30% higher in Denmark,
      Poland, Estonia and Slovenia for oesophageal cancer and in Denmark, England,
      Scotland and Poland for gastric cancer. In the other countries survival figures
      were close to the European average. Gender had little influence on survival,
      whilst age at diagnosis was inversely related to prognosis. There was a slight
      improvement between 1978 and 1989 in 5-year overall relative survival rates for
      both oesophageal cancer (RR = 0.80, 95% confidence interval (CI) 0.72-0.90) and
      gastric cancer (RR = 0.88, 95% CI 0.82-0.94). Differences in quality of care and
      stage at diagnosis can explain in part the differences in survival found in the
      EUROCARE countries. Significant improvement in prognosis has still to be
      achieved.

PMID- 10070284
TI  - Survival of colorectal cancer patients in Europe during the period 1978-1989.
      EUROCARE Working Group.
AB  - This study concerns the survival of European patients diagnosed between 1978 and
      1989 with colorectal cancer. Variations in survival in relation to age, country
      and period of diagnosis were examined. Data from the EUROCARE study were supplied
      by population-based cancer registries in 17 countries to a common protocol. Five
      years after diagnosis, relative survival rates were 47 and 43% for cancers of the
      colon and rectum, respectively. Survival decreased with increasing age: the
      relative risk of dying for the oldest patients (75+) was 1.39 for rectum and 1.54
      for colon compared with the youngest patients (15-44 years). In 1985-1989
      survival from colorectal cancer differed significantly between different European
      countries: the Nordic countries (Denmark excluded), The Netherlands, Switzerland,
      France and Austria were characterised by high survival, whilst Eastern European
      countries, the U.K. and Denmark were characterised by low survival. There was a
      general improvement in survival over the period 1978-1989: from 40 to 48% for
      colon cancer and 38 to 46% for rectal cancer. For neither cancer site did between
      country survival differences narrow over the study period. Intercountry and time
      differences in survival differences are probably related to stage at diagnosis
      and postoperative mortality.

PMID- 10070285
TI  - Survival of patients with primary liver cancer, pancreatic cancer and biliary
      tract cancer in Europe. EUROCARE Working Group.
AB  - The EUROCARE Study is a European Union project to assemble survival data from
      population-based cancer registries and analyse them according to standard
      procedures. We investigated and compared liver, pancreatic and biliary tract
      cancer survival in 17 countries from 1985 to 1989. Time trends in survival over
      the 1978-1989 period were also investigated in 12 countries. The overall European
      mean 1 year relative survival was 16% for primary liver cancer, 26% for biliary
      tract cancer and 15% for pancreatic cancer. The corresponding 5-year relative
      survival was 5, 12 and 4%, respectively. Taking the European average as the
      reference, the relative risk (RR) of death was at least 20% higher for the three
      cancers in Denmark and Estonia. Survival tended to be higher in Spain for primary
      liver cancer and biliary tract cancer. Gender had little influence on survival
      whilst age at diagnosis was inversely related to prognosis. There was an
      improvement in 1-year relative survival rate for primary liver cancer: relative
      risk (RR) of 0.68 (95% confidence interval (CI) of 0.60-0.77) for 1987-1989
      versus 1978-1980 and biliary tract cancer (RR 0.77, 95% CI 0.68-0.87). There was
      less variation in 5-year relative survival rate over time. Some intercountry
      survival differences for primary liver, biliary tract and pancreatic cancers
      exist over Europe. Differences in quality of care, in particular treatment
      aggressiveness, may explain some of these differences in survival. New approaches
      to the management of these cancers need to be found.

PMID- 10070286
TI  - Variation in survival of patients with lung cancer in Europe, 1985-1989. EUROCARE
      Working Group.
AB  - In this study, we report on the variation in the prognosis for adult patients
      with lung cancer within Europe, by age, histology and country from 1985-1989. We
      considered trends in survival since 1978 for most countries. Survival analysis
      was carried out on 173,448 lung cancer cases diagnosed between 1985 and 1989 in
      44 population-based cancer registries, participating in the EUROCARE study.
      Relative 1-year survival rates for patients with lung cancer varied from 24 to
      40%, being highest in Finland, France, The Netherlands and Switzerland and lowest
      in Denmark, England, Poland and Scotland. Half of all patients under the age of
      45 years died within 1 year of diagnosis, increasing to almost 80% for those aged
      75 years or older. Whilst the prognosis for patients with non-small cell
      carcinoma remained more or less constant between 1978 and 1989 (25% in Denmark
      and 44% in Finland), that for patients with small cell carcinoma improved
      slightly, especially in The Netherlands (Eindhoven from 17 to 24%) and
      Switzerland (Geneva from 24 to 32%). In conclusion, a fairly large variation in
      lung cancer relative survival rates existed between European countries. The most
      likely explanation for the differences is the variation in access to specialised
      care. Except for a slight improvement in short-term survival for patients with
      small cell lung cancer, survival has remained poor since 1978.

PMID- 10070287
TI  - Improving survival of melanoma patients in Europe since 1978. EUROCARE Working
      Group.
AB  - Within the EUROCARE study 45 cancer registries have contributed survival data on
      3.5 million cancer sufferers within 17 countries in Europe. This paper reports on
      survival in 16,113 cutaneous malignant melanoma cases diagnosed between 1985 and
      1989. Relative survival rates were calculated according to the Hakulinen computer
      program with data stratified according to country, age group and period of
      diagnosis. Relative 5-year survival was higher in women (81%) than in men (69%)
      but there was wide variation in relative survival across Europe at both 1 and 5
      years, ranging at 5 years between 54 and 89%. At both 1 and 5 years, survival was
      lowest in the Eastern countries. Between 1978 and 1989 there was an improvement
      in survival rates probably attributable to the detection of increasing
      proportions of better prognosis, thinner tumours. In the younger age groups, this
      may be related to public awareness campaigns. The discrepancy in survival between
      men and women also narrowed. The single most important prognostic factor is the
      depth of invasion at diagnosis and there is some evidence that underlying
      variation in stage at presentation as well as histological type accounts for much
      of the observed variation in survival.

PMID- 10070288
TI  - Variations in survival from breast cancer in Europe by age and country, 1978
      1989. EUROCARE Working Group.
AB  - The objective of this study, part of the wider EUROCARE II collaborative project,
      was to examine variations by age and country in the relative survival of women
      from breast cancer in Europe, based on data fro 145,000 cases in 1985-1989 and
      trends based on (245,000) cases for 1978-1989. Data were supplied by 42 cancer
      registries in 17 countries to a common protocol. Results for some countries where
      the participating registries covered only small proportions of the total
      population may not be representative of the whole country. In 1985-1989 there
      were wide differences among the 17 countries: survival was above the European
      average in Iceland, Finland, Sweden, Switzerland, France and Italy; around
      average in Denmark, The Netherlands, Germany and Spain; below average in
      Scotland, England and Slovenia; and well below average in Slovakia, Poland and
      Estonia. In France, Spain and Italy, but not in the U.K., there were wide
      differences in survival among the participating registries. Survival generally
      declined with age, particularly in the elderly (75 years and over)--this was most
      marked in Denmark, Scotland and England. Over the period 1978-1989, 1-year
      survival improved by 2% overall and 5-year survival by 6%. There were
      improvements in 5-year survival in all countries except Iceland, Germany,
      Switzerland and Estonia, and in all age groups except the youngest (15-44 years).
      It is likely that differences in the access to and quality of care in the various
      countries played a large part in explaining the differences in survival.

PMID- 10070289
TI  - Survival of adult patients with cancer of soft tissues or bone in Europe.
      EUROCARE Working Group.
AB  - Using data from the EUROCARE II database, relative survival rates for Europe were
      studied for adult patients with soft tissue sarcomas (STS) and bone cancers
      separately. Altogether 2,151 bone cancers and 5,845 STS were included. Survival
      analysis was carried out for each gender and the ratio between observed and
      expected survival calculated. One-year relative survival for bone cancer was 65%
      in men and 71% in women, and 5-year relative survival 45% in men and 51% in
      women. For STS 1-year relative survival was 78% for men and 79% for women and 5
      year relative survival was 59% for both sexes. The variation in relative survival
      for bone cancer between countries was substantial, with the lowest rates seen in
      the Eastern countries. Denmark had the lowest rates of the Nordic countries,
      similar to those of Scotland. The variation in survival rates for STS was less
      pronounced, but still rates tended to be lower in Eastern European countries. The
      present analysis was carried out in the subset of European STS excluding visceral
      STS. To assess fully the international variation in survival a review of STS
      based on reported sarcoma morphology must be carried out.

PMID- 10070290
TI  - Survival of European women with gynaecological tumours, during the period 1978
      1989. EUROCARE Working Group.
AB  - This study concerns the survival of European patients diagnosed between 1978 and
      1989 with cancer of corpus and cervix uteri and ovary. Variations in survival in
      relation to age, country and period of diagnosis were examined. Data from the
      EUROCARE study were supplied by population-based cancer registries in 17
      countries to a common protocol. Five years after diagnosis, relative survival
      rates were 75, 62 and 35% for cancers of the endometrium, cervix and ovary,
      respectively. Survival decreased markedly with age. The decrease was especially
      evident for ovarian cancer, which declined from 65% (15-45 years) to 18% (75+
      years). In 1985-1989 there were important inter-country differences in survival
      for European women with gynaecological cancers: Eastern European countries were
      characterised by low 5-year relative survival whilst in Sweden, Austria, The
      Netherlands and Switzerland survival was generally higher than for other European
      countries. From 1978-1989, 5-year relative survival improved slightly for
      cervical cancer and improved more among the oldest patients. Prognosis also
      improved slightly for patients with ovarian tumours and this increase (around
      20%) was concentrated among patients between 15 and 64 years of age. Intercountry
      differences in survival did not in general reduce over time, although for ovarian
      cancer survival differences narrowed probably in relation to the more widespread
      use of more effective chemotherapy. Intercountry and time differences in survival
      for cervical cancer are almost certainly related to variations in the
      effectiveness of cervical screening programmes. For corpus uteri cancer there was
      no improvement in survival over the period of this study and intercountry
      survival differences for this cancer are probably related to differences in
      patient management.

PMID- 10070291
TI  - Variation in survival of patients with prostate cancer in Europe since 1978.
      EUROCARE Working Group.
AB  - Since the incidence of prostate cancer has increased considerably over the past
      two decades in most European countries, knowledge of the variation in survival is
      pertinent. The collaboration across Europe in the EUROCARE study has now been
      extended to 45 registries in 17 countries. We report on variation in relative
      survival according to age of 65,728 patients diagnosed with prostate cancer
      between 1985 and 1989 and also explore time trends since 1978 for most countries.
      Considerable variation in survival was found within and between countries, with
      the highest survival in Switzerland (5-year relative survival 72%), followed by
      Germany (67%) and the Nordic countries (except Denmark). The lowest survival was
      found in Estonia (39%), preceded by Slovenia (40%), Denmark (41%) and England
      (45%). Between 1978 and 1986, relative survival barely changed over time, but it
      improved from 55% (95% confidence interval [CI] 53-57) during 1984-1986 to 59%
      (CI 56-61) during 1987-1989. A small but unexpected deterioration of survival for
      patients aged between 45 and 54 years from 61% to 56% was observed in the early
      1980s. It is likely that variation in both detection methods and treatment plays
      a role in the observed variation in survival, but more information is needed to
      assess each contribution.

PMID- 10070292
TI  - Improvement in survival of patients with cancer of the kidney in Europe. EUROCARE
      Working Group.
AB  - Survival of adult patients with cancer of the kidney, renal pelvis, ureter and
      urethra (ICD-9 189) was analysed using data from the EUROCARE II study, a
      collaborative project of 45 population-based cancer registries in 17 European
      countries. For the period 1985-1989, more than 24000 patients were included and 5
      year relative survival was 48%. Large variations were observed between countries
      with 5-year relative survival ranging from 57% in France, 53% in Italy and 51% in
      Spain to 35% in Denmark, 33% in Poland and 30% in Estonia. A number of registries
      also provided information on previous years and survival was seen to improve with
      time from 44% in 1978-1980 to 50% in 1987-1989. Age was an important determinant
      of survival with 5 year survival rates decreasing from 63% in patients aged 15-44
      years to 36% in patients aged 75 years and older. Variation in survival rates by
      country or time is probably related to differences in the distribution of tumour
      stage at diagnosis. Evidence to confirm this theory is, however, lacking.

PMID- 10070293
TI  - Improved survival for patients with testicular cancer in Europe since 1978.
      EUROCARE Working Group.
AB  - Within the framework of EUROCARE, a population-based study on survival and care
      of cancer patients in Europe, we analysed survival of 7426 men with testicular
      cancer diagnosed between 1985 and 1989 in 17 countries. For comparison between
      the countries, survival rates were age-standardised to the age structure of the
      entire study population. Among the participating countries of Northern, Western,
      Central and Southern Europe and the U.K., the age-standardised 5-year relative
      survival rate varied from 89% (Finland) to 93% (Spain, Germany). In Eastern
      Europe, the rate ranged from 48% (Estonia) to 84% (Slovenia). Rates in Poland,
      Slovakia and Estonia were significantly lower than the summary rate for Europe (P
      < 0.05). Relative survival generally decreased with the age of patients at
      diagnosis. Based on the weighted analysis of pooled European data, the 5-year
      relative survival rate was 91% for patients aged 15-44 years; 85% for patients
      aged 55-64 years; and 59% for patients aged 75 years and over. The time trend in
      survival by 3-year periods between 1978 and 1989 was studied on the basis of
      12,084 cases provided by 12 countries. From 1978-1980 to 1987-1989, the 5-year
      relative survival rate for Europe increased from 79 to 93% (P < 0.05). The
      inequalities in survival between the more developed European countries were more
      notable in the 1970s than in the 1980s, suggesting that the treatment for
      testicular cancer became standardised in the latter period. Poorer survival in
      Eastern Europe and particularly in Estonia, could be related to later
      introduction of the effective cytotoxic treatments, but also to longer diagnostic
      delay and limited availability of modern staging procedures.

PMID- 10070294
TI  - Survival rates for primary malignant brain tumours in Europe. EUROCARE Working
      Group.
AB  - In the framework of EUROCARE, a concerted action between 45 population-based
      cancer registries, in 17 European countries, survival of patients with primary
      malignant brain tumours was investigated. Survival analysis was carried out on
      16,268 patients diagnosed between 1985 and 1989 and followed-up for at least 5
      years. The mean European age-standardised 5-year relative survival was 17% in men
      and 20% in women, with minimal intercountry variations, except for markedly lower
      rates in Scotland, Estonia and Poland. The age-specific analysis showed a
      relatively uniform survival in patients aged more than 65 years at diagnosis, but
      there were more marked intercountry differences in younger patients. In the 15-44
      year age group (25% of the total study population) 5-year relative survival
      ranged between 55% (Finland and Sweden) and 27% (Poland). Generally, survival
      decreased with increasing age at diagnosis. The analysis of a temporal trend in
      survival was carried out on a subset of registries with available data from 1978
      1989. Overall, there was an increase in survival over the considered study
      period, mostly confined to 1-year survival, suggesting that it was mostly related
      to improved diagnostic techniques. The most important survival increase occurred
      in the younger patients, both for 1- and 5-year survival, suggesting that younger
      patients have less biologically aggressive tumours, benefiting from the combined
      effect of diagnostic accuracy and effective therapies. The most marked survival
      increase was seen in England and Denmark, countries with low survival rates at
      the beginning of the study period, whereas in Finland and Germany, where survival
      was relatively high to begin with, no important temporal trend was seen.

PMID- 10070295
TI  - Variation in survival of adult patients with thyroid cancer in Europe. EUROCARE
      Working Group.
AB  - The survival of patients with thyroid cancer was analysed using population-based
      EUROCARE II data from 1978-1989 (trends in survival) and 1985-1989 (cross
      sectional comparisons between areas). The data consisted of 7504 patients and
      covered 37 cancer registration areas in 17 European countries. In 90% of the
      patients the diagnosis was histologically confirmed. The prognosis of patients
      with thyroid cancer was relatively favourable. The overall 5-year relative
      survival rate was 72% for men and 80% for women. Substantial variation in this 5
      year rate was observed between countries ranging from 59 to 83% in men and from
      72 to 84% in women. Higher than average survival rates were observed in Finland,
      Iceland, The Netherlands and Sweden. Countries with lower than average rates were
      Denmark, England, Estonia, Slovakia, Slovenia and Poland (women). Elderly
      patients had lower survival rates than the younger ones. Time trends in survival
      (which could be analysed only in selected countries with sufficient numbers of
      cases) were irregular but generally showed slight increases compared with rates
      in 1978-1980. Different distributions in the histological subtypes of thyroid
      cancer is one plausible explanation for the variation in the survival rate. Other
      likely factors contributing to this are differences in the stage distribution and
      varying efficacy of treatment. The EUROCARE II data did not permit specific
      analyses of the roles of various prognostic factors.

PMID- 10070296
TI  - Variation in survival of adult patients with haematological malignancies in
      Europe since 1978. EUROCARE Working Group.
AB  - Data on 73,070 patients for seven major haematological malignancies diagnosed in
      Europe between 1985 and 1989 from 39 population-based cancer registries in 17
      countries are included in the EUROCARE database. Relative survival was analysed
      by country and age between 1985 and 1989 and time trends were analysed from 1978
      1989 for 13 countries which collaborated in EUROCARE for this entire period. The
      European weighted age-standardised 5-year relative survival rate was 72% for
      patients with Hodgkin's disease (HD, ranging from 45 to 76% in 13 countries), 63%
      for chronic lymphocytic leukaemia (CLL, range 51-79%, 14 countries), 46% for
      patients with non-Hodgkin's lymphoma (NHL, range 25-63%, 17 countries), 31% for
      patients with chronic myelocytic leukaemia (CML, range 8-40%, 13 countries), 28%
      for patients with multiple myeloma (MM, range 18-36%, 14 countries), 25% for
      patients with acute lymphoblastic leukaemia (ALL, range 19-33%, 7 countries) and
      10% for patients with acute myeloblastic leukaemia (AML, range 4-15%, 11
      countries). In all countries, relative survival declined with age, most markedly
      for patients with acute leukaemias. Patients in Northern and Western Europe had
      better survival rates, particularly in younger patients (15-45 years of age),
      whilst those in Eastern European countries tended to have poorer rates. Compared
      with 1978-1979, relative 5-year survival improved in 1987-1989 for most
      haematological malignancies (relative risk (RR) of death for CLL 0.65, AML 0.75,
      HD 0.76, ALL 0.79, NHL 0.82), with only CML (RR 0.95) and MM (RR 1.00) showing
      little or no change. These results suggest that generally and particularly in
      Eastern Europe there is room for improvement in the diagnosis and treatment of
      haematological malignancies. The intercountry differences also highlight the
      importance of socio-economic conditions to health status.

PMID- 10070297
TI  - Relative survival in elderly cancer patients in Europe. EUROCARE Working Group.
AB  - In this paper different patterns of survival by age and gender are presented for
      17 European countries which participated in the EUROCARE II programme. Survival
      data were available for 701,521 patients aged between 65 and 99 years from 44
      population-based cancer registries. Age-standardised relative survival rates at 1
      and 5 years from diagnosis were computed. Relative risks (RRs) of death for those
      aged between 65 and 99 years compared with those aged between 55 and 64 years
      were estimated by gender and country. In general, the elderly had a large
      survival disadvantage, particularly 1 year after diagnosis and in women. Poorer
      survival rates in the elderly were observed for patients from Eastern European
      countries for almost all sites. However, relative survival of the elderly with
      respect to younger patients was similar in the different geographic areas. The
      results are in agreement with other population-based studies, confirming a worse
      prognosis for the elderly in both sexes. This may be explained by changes in
      biology and the natural history of the tumour and the occurrence of severe
      comorbidities, potentially affecting preventive, diagnostic and therapeutic
      strategies. The lack of equality in providing adequate treatment to elderly
      cancer patients should be addressed as a matter of urgency by health-care
      providers.

PMID- 10070298
TI  - The prognostic role of gender in survival of adult cancer patients. EUROCARE
      Working Group.
AB  - Many observations indicate that women have a much longer expectancy of life than
      men. Some population-based studies on cancer patients support the idea of the
      role of gender in predicting survival. However, the data are somewhat contrasting
      and inconclusive. The purpose of this paper was to evaluate the prognostic role
      of gender for cancer patients, making use of the large set of survival data made
      available by the EUROCARE II project for the period 1985-1989. By applying a
      multivariate approach the major confounders such as age, geographical area and
      cancer site were considered in analysing survival data on more than 1 million
      cancer cases collected by 45 population-based cancer registries in 17 European
      countries. The results were consistent with the general observation that in the
      industrialised countries women tend to survive longer than men. The multivariate
      analysis showed better survival from cancer in women than in men, estimated as an
      overall 2% lower relative risk of dying. The female advantage was particularly
      evident in young cases, reduced in patients in middle age groups and in the
      oldest patients completely reversed so that at this age men had the better
      prognosis. Longer survival for women was not present immediately after diagnosis,
      but the major advantage was seen after 3 years of follow-up. The risk of death
      for women was significantly lower for cancer of the head and neck, oesophagus,
      stomach, liver and pancreas. For bladder cancer, the risk of death was
      significantly greater for women. These results can be explained by gender
      differences in sub-site distributions (head and neck and stomach) and by the
      differences in the stage at diagnosis (presumably bladder). However, the
      consistency of the data, evident only when a vast set of data is analysed,
      suggest that women may be intrinsically more robust than men in coping with
      cancer.

PMID- 10070299
TI  - Psychological sequelae of screening women with a family history of breast cancer.

PMID- 10070300
TI  - Are platinum compounds mandatory in the treatment of metastatic non-small cell
      lung cancer?

PMID- 10070301
TI  - Evolving perspectives in contralateral breast cancer.
AB  - Despite extensive publications reviewing contralateral breast cancer (CBC), the
      role of screening and preventative measures for contralateral tumours is
      controversial and optimal clinical management remains undefined. This paper
      addresses the incidence, the predisposing factors, the prevention and the
      treatment of bilateral breast cancer based on a review of the literature. Risk
      factors for CBC include young age at primary breast cancer diagnosis, hereditary
      breast cancer (due to a germline mutation), familial breast cancer (one or more
      affected relatives), radiation exposure at a young age, lobular carcinoma in situ
      (LCIS), lobular invasive carcinoma and multicentricity. Retrospective studies
      suggest that contralateral mammographic surveillance results in the early
      detection of breast cancer, but no clear survival benefit has been demonstrated.
      Trials of adjuvant tamoxifen in breast cancer patients have shown a reduction in
      the incidence of CBC in both pre- and postmenopausal women. In addition, breast
      cancer patients treated with ovarian ablation and prednisone have significantly
      reduced CBC versus controls. In patients with primary breast cancer there is no
      evidence that contralateral breast biopsies or contralateral prophylactic
      mastectomy reduce mortality. Randomised, prospective trials to determine optimal
      surveillance, prevention and treatment strategies for the contralateral breast in
      breast cancer patients have not been conducted. Based on the published
      literature, contralateral breast surveillance in breast cancer patients
      reasonably includes breast self-examination, regular physical examinations and
      annual mammography. In women who have no evidence of distant metastasis at the
      time of CBC diagnosis, we recommend that the CBC be treated in the same manner as
      a first breast cancer, taking into account prior local and systemic therapy.

PMID- 10070302
TI  - Breast screening: the psychological sequelae of false-positive recall in women
      with and without a family history of breast cancer.
AB  - The psychological effects of false-positive mammography were evaluated in 124
      women who had taken part in the U.K. National Health Service Breast Screening
      Programme. In addition, the effects of recall on women with and without a family
      history were compared. These women were asked to complete the Hospital Anxiety
      and Depression Scale (HADS) before being invited to attend for screening, at
      recall and 5 weeks and 4 months after recall. At screening and at recall, the
      women were asked to complete the Health Questionnaire (HQ) which measures stress
      related behaviour changes in the previous week. In the week before screening,
      compared with women who did not have a family history of breast cancer, women
      with a family history had lower scores on HADS depression and reported fewer
      stress-related behaviour changes. At recall, regardless of family history, the
      women were more likely to have borderline or clinically significant anxiety than
      at baseline or screening. Nevertheless, for most women, recall-induced anxiety
      was relatively transient (less than 5 weeks). Compared with women without a
      family history, women with a family history were more anxious 4 months after
      recall, although their anxiety scores tended to be lower (P < 0.06) than at
      baseline. A strength of the present study is that the initial baseline measure
      was uncontaminated by the screening process. Women who did not complete
      questionnaires at one or more of the subsequent time points scored higher on HADS
      depression at baseline, indicating that the results are likely to have
      underestimated the effects of recall. Screening appears to be less stressful for
      women with a family history than for those without a history. However, for both
      groups recall causes short term distress. Breast screening programmes should
      ensure that steps are taken to minimise the number of women who are recalled for
      unnecessary investigations.

PMID- 10070303
TI  - Cost of care in a randomised trial of early hospital discharge after surgery for
      breast cancer.
AB  - The aim of this study was to determine the effect of the reduction of the length
      of hospital stay after surgery for breast cancer on the rate of care consumption
      and the cost of care. Patients with operable breast cancer were randomised to a
      short or long postoperative hospital stay. Data on care consumption were
      collected for a period of 4 months in diaries administered by patients, and
      socioeconomic status was evaluated by questionnaires. A cost minimisation
      analysis using the 'societal' perspective was performed and savings were compared
      with the savings of hospital charges. The use of professional home care was
      higher for the short stay group during the first month (7.2 versus 1.3 h, P <
      0.0001). The number of out-patient consultations, the intensity of informal home
      care and patient's expenses did not increase after early discharge. The total
      cost of care was reduced by US$1320 by introducing the short stay programme (P =
      0.0007), but the savings were substantially lower than the savings in hospital
      charges (US$2680).

PMID- 10070304
TI  - Markers of bone resorption in patients treated with pamidronate.
AB  - Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers
      of bone resorption. In cancer patients with bone metastases, NTX is more often
      elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts
      and their treatment decreases skeletal complications of malignancy. The aim of
      this study was to correlate urinary PYD, DPD, and NTX levels with clinical events
      in patients receiving pamidronate. 25 cancer patients with lytic bone disease
      were treated with monthly pamidronate combined with endocrine or chemotherapy; 27
      others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3
      and 6 months. NTX values were determined by enzyme-linked immunosorbent assay
      (ELISA); PYD and DPD values were determined by reverse phase high performance
      liquid chromatography (HPLC). Two hour urines were also collected weekly for 21
      patients. The greatest difference as a result of pamidronate treatment was
      observed in NTX values. Maximum suppression was achieved 2 weeks after treatment.
      Of the 25 patients who received pamidronate, 21 had initially elevated NTX
      values. 12 of the 21 finished with normal NTX values, whilst 9/21 had NTX values
      which remained abnormally elevated. The proportions of patients with fractures
      between these two subgroups approached statistical significance (P = 0.07) while
      the proportions with bony disease progression were significant (P = 0.03,
      Fisher's exact test). Measuring NTX levels appears useful in monitoring
      bisphosphonate therapy of bone metastases. The goal of treatment should be to
      normalise NTX excretion.

PMID- 10070305
TI  - A phase II study of combination paclitaxel and carboplatin in advanced
      nasopharyngeal carcinoma.
AB  - The aim of this study was to determine the efficacy and toxicity of combination
      paclitaxel and carboplatin chemotherapy in patients with metastatic and/or
      locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with metastatic
      and/or locoregionally advanced NPC were treated with carboplatin calculated
      according to an AUC of 6 mg ml/min (based on Calvert formula) given as an
      intravenous (i.v.) bolus, followed by paclitaxel 135 mg/ml2 given as an i.v.
      infusion over 3 h with standard premedication. Cycles were given 3 weekly to a
      maximum of six. From January 1996 to November 1997, 27 patients were entered and
      assessable for response and toxicity. A total of 122 cycles were given and the
      median number of cycles given was five. The overall response rate was 59%
      (16/27). There were 3 (11%) complete responses, 13 (48%) partial responses, 5
      (19%) static disease and 6 (22%) progressive disease. Toxicity was mainly
      haematological including: grade 3/4 neutropenia (39 cycles, 32%), grade 3/4
      anaemia (nine cycles, 7%), grade 3/4 thrombocytopenia (eight cycles, 7%). There
      were three episodes of neutropenic fever (3%). Non-haematological toxicities were
      mild and infrequent. Paclitaxel and carboplatin combination chemotherapy is
      active in NPC and has tolerable toxicity. Further study with dose escalation is
      required to assess its optimal efficacy.

PMID- 10070306
TI  - Docetaxel (Taxotere) plus cisplatin: an active and well-tolerated combination in
      patients with advanced non-small cell lung cancer.
AB  - The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin
      100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was
      investigated in 51 chemotherapy naive patients with locally advanced or
      metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with
      a median age of 54 years and median performance status of 1; 80% of patients had
      metastatic disease, including 37% with bone involvement. All patients received
      prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and
      standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of
      42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%);
      the median response duration was 7.3 months, median survival 8.4 months, and 1
      year survival rate 35%. The most common adverse event was neutropenia, occurring
      in two-thirds of patients. Neurosensory effects were cumulative but generally
      mild. No treatment-related deaths occurred. This combination of
      docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly
      superior to single-agent docetaxel, due to differences in prognostic factors
      among the patients in open trials, a randomised study would be needed to
      demonstrate definitively whether cisplatin adds to the activity of docetaxel or
      not.

PMID- 10070307
TI  - Abnormal expression of p120 correlates with poor survival in patients with
      bladder cancer.
AB  - p120 is a cytoplasmic molecule closely associated with the Ca(2+)-dependent cell
      cell adhesion molecule E-cadherin, by forming complexes between the cytoplasmic
      domain of E-cadherin and the cytoskeleton. Although it has been shown that loss
      or downregulation of E-cadherin is associated with an invasive and poorly
      differentiated phenotype in several tumours, there is very little information
      available concerning p120 expression in malignant disease. We used an avidin
      biotin immunoperoxidase technique to examine the immunoreactivity and cellular
      localisation of p120 and E-cadherin in 68 transitional cell carcinomas (TCC) and
      14 normal bladder biopsies and correlated these results with pathological and
      clinical parameters. E-cadherin and p120 were expressed in a normal membranous
      pattern in all normal bladder epithelium specimens. Loss of normal surface E
      cadherin and p120 expression was found in 52/68 (76%) and 57/68 (84%) tumours,
      respectively. There was a significant correlation between the loss of normal
      membranous expression of p120 and increased grade (P < 0.001) and T stage (P <
      0.001). The abnormal expression of p120 was correlated with poor survival (P <
      0.05). Our data indicate that the E-cadherin-p120 complex may be a useful
      prognostic marker in bladder cancer.

PMID- 10070308
TI  - Clinical significance of plasma vascular endothelial growth factor in
      gastrointestinal cancer.
AB  - Circulating vascular endothelial growth factor (VEGF) was measured in gastric and
      colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA).
      Firstly, serum and plasma samples were collected from 20 normal controls to
      compare the values of VEGF and to determine which specimen type was most suitable
      for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF
      levels under the limit of detection (15 pg/ml) and the levels of the remaining
      three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated
      high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time
      course test of two normal controls serum VEGF values increased markedly between
      30 and 60 min and remained high, whilst plasma VEGF values were low up to 480
      min. Thus, plasma samples are more suitable for the measurement of circulating
      VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer
      (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with
      colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8
      advanced without metastasis and 18 metastatic) before treatment. An extremely
      high plasma concentration of VEGF was seen in some cancer patients with
      metastasis. To discriminate these patients, a cut-off level was determined,
      considering both the distribution of the sample concentration and the upper limit
      of 95% confidence area of VEGF in the cancer patients without metastasis. The cut
      off value was 108 pg/ml and most cancer patients without metastases had VEGF
      levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients
      (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels
      were higher than the cut-off value. Survival was also analysed in the patients
      with metastasis. It was significantly longer in the patients with low VEGF levels
      (below the cut-off) than in those with high VEGF levels (logrank test, P =
      0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer)
      were treated with systemic chemotherapy, and their pretreatment levels of plasma
      VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation
      to response. The response to chemotherapy was significantly higher in patients
      with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P =
      0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma
      VEGF is a useful marker for tumour metastasis and patient survival, and a
      possible predictive factor for the response of patients with gastrointestinal
      cancer to chemotherapy.

PMID- 10070309
TI  - Expression of p68 protein kinase and its prognostic significance during IFN-alpha
      therapy in patients with carcinoid tumours.
AB  - The aim of this study was to evaluate the antiproliferative effects of interferon
      alpha (IFN-alpha) on neuroendocrine differentiated cell lines and,
      retrospectively, to assess the prognostic significance of p68 protein kinase
      (PKR) induction in neuroendocrine gut and pancreatic tumour patients. Archive
      specimens from 56 patients were studied, 43 before IFN-alpha and 56 during
      therapy. The tissues were immunostained for p68 protein kinase (PKR) using the
      monoclonal antibody (MAb) TJ4C4. A significant increase in immunostaining after
      treatment with IFN-alpha compared with before treatment (3.47 +/- 0.12 versus
      2.72 +/- 0.15, P < 0.001) was noted. The p68 score was significantly increased
      after treatment only in patients with stable disease before = 2.71 +/- 0.19,
      after = 3.40 +/- 0.14 (P < 0.001) or an objective response before 3.13 +/- 0.22,
      after = 4.00 +/- 0.24 (P < 0.05) but not in those with progressive disease
      (before = 2.32 +/- 0.24, after 2.86 +/- 0.26, NS). A low p68 score (< 3.0) during
      treatment was a predictor of shorter duration of response and overall survival (P
      = 0.0062 and P < 0.0001, respectively). Furthermore, IFN-alpha showed a
      significant antiproliferative effect (by [3H]thymidine incorporation) on two
      carcinoid tumour cell lines in a dose-dependent manner which correlated with a
      dose-dependent induction of p68 mRNA and protein expression (by Northern and
      Western blot analysis). We conclude that IFN-alpha can effectively inhibit the in
      vitro growth of carcinoid tumor cell lines and upregulates the expression of p68
      at both mRNA and protein levels in carcinoid tumours. The induction of p68 could
      be a prognostic indicator of response in patients with carcinoid tumours during
      IFN-alpha treatment.

PMID- 10070310
TI  - K-ras mutations in colorectal adenocarcinomas and neighbouring transitional
      mucosa.
AB  - The K-ras gene in codons 12 and 13 was investigated using allele-specific
      polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa
      (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas.
      K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69
      (6%) of transitional mucosa samples, but not in the normal mucosa. Further,
      mutation rates were increased in younger patients (P = 0.001) and in mucinous
      carcinomas (50%) compared with well differentiated (17%), moderately
      differentiated (26%) or poorly differentiated (24%) tumours. Our findings
      indicate that mucinous carcinoma may represent a distinct genetic entity.

PMID- 10070311
TI  - A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone)
      chemotherapy in childhood Hodgkin's disease.
AB  - The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or
      without involved field radiotherapy, has been shown to be an effective treatment
      in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both
      alkylating agents and radiotherapy this regimen has been studied in a series of
      54 children and young adults. Early analysis suggested that the relapse rate was
      higher with VEEP than with standard alkylating agent-based regimens. Sufficient
      follow-up has now been achieved to evaluate the likelihood of sustained remission
      following second-line treatment and therefore the overall long term survival with
      this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression
      Free Survival (PFS) for patients with stage I-III disease was 93% and 82%
      respectively. However, the 5-year OS and PFS for stage IV patients was only 44%
      and 50%, respectively. Of 13 patients who were initial treatment failures on
      VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line
      therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2
      relapses in those achieving a partial response (PR) (n = 8). All those relapsing
      from CR/PR were salvaged by second-line alkylating agent chemotherapy +/-
      radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I
      IIIA, non-bulky disease, the moderately high relapse rate did not adversely
      affect the overall high cure rate, although VEEP failures were subjected to a
      high total treatment burden. VEEP alone is inadequate in patients with stage IV
      disease, bulky mediastinal disease in/or those with B symptoms in whom there is a
      high primary failure rate and relatively poor results with second line therapy.

PMID- 10070312
TI  - Survival and distribution pattern of childhood liver cancer in Taiwan.
AB  - Studies of survival and distribution of liver cancer in children are scarce. In
      this study, using data from the cancer registry of Taiwan, from 1979 to 1992, we
      identified 377 young patients (0-15 years of age) suffering from liver cancer,
      coded 155 according to the International Classification of Diseases. Among these
      patients, 122 were histopathologically proven hepatocellular carcinoma (HCC) and
      43 hepatoblastoma (HB). For survival analysis, we also searched for cases of
      liver cancer in 0-16 year old children in the Taiwan cancer registry for the
      period between 1988 and 1992. We found 109 cases with identification numbers and
      birth dates which allowed our cases to be linked with the death registry of the
      National Health Department of Taiwan enabling the calculation of 5-year survival
      rates using actuarial life tables. Between 1979 and 1992, for 122 HCC cases,
      there was a peak incidence at the age of 1 year, then a decline to a trough at
      the age of 4 years, after which the number of cases increased to the age of 15
      years. After the age of 4 years boys outnumbered the girls by 2:1. 36 (84%) of 43
      HB cases were under the age of 5 years and boys tended to outnumber girls by
      2.9:1. Between 1988 and 1992, of the 109 patients, 49 were diagnosed
      histopathologically and 60 patients clinically. Their overall 5-year survival
      rate was 19%. The 5-year survival rate of the 28 HCC patients was 17%, whereas
      that of the 17 HB patients was 47%. In conclusion, our epidemiological findings
      indicate that the HCC distribution among children is different according to age
      and to some extent sex. The overall 5-year survival rate of children suffering
      from liver cancer was still unfavourable.

PMID- 10070313
TI  - Soft tissue sarcoma after treatment for breast cancer--a Swedish population-based
      study.
AB  - The aim was to quantify the risk of post-treatment sarcoma in breast cancer
      patients. All 122,991 women with a breast cancer from 1958 to 1992 in the Swedish
      Cancer Register were followed up for soft tissue sarcomas and 116 were found,
      giving a standardised incidence ratio of 1.9 (95% CI 1.5-2.2). The absolute risk
      was 1.3 per 10(4) person-years. The sarcomas were located in the breast region or
      on the ipsilateral arm in 63% (67/106). There were 40 angiosarcomas and 76
      sarcomas of other types. In a case-control study, angiosarcoma correlated
      significantly with lymphoedema of the arm, odds ratio (OR) 9.5 (95% CI 3.2-28.0),
      but no correlation with radiotherapy was observed. For other types of sarcoma
      there was a correlation with the integral dose. The dose-response relationship
      indicated that the risk increased linearly with the integral dose to 150-200 J
      and stabilised at higher energies. The OR was 2.4 (95% CI 1.4-4.2) for an energy
      of 50 J, approximately corresponding to the radiation of the breast after breast
      conserving surgery. Thus, only oedema of the arm correlated with angiosarcoma,
      but for other types of sarcoma the integral dose of radiotherapy was a predictor
      of the risk.

PMID- 10070314
TI  - Mapping loss of heterozygosity at chromosome 13q: loss at 13q12-q13 is associated
      with breast tumour progression and poor prognosis.
AB  - Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast
      carcinoma and are thought to harbour tumour suppressor genes (TSG). At chromosome
      13q, two TSGs have been identified, RB1 at 13q14 and BRCA2 at 13q12-q13. In this
      study, 139 sporadic breast tumours were analysed with 18 polymorphic
      microsatellite markers for detailed mapping of LOH at chromosome 13q and
      evaluation of an association with known progression factors. LOH with at least
      one marker was observed in 71 (51%) of the tumours analysed. The deletion mapping
      indicated three LOH target regions, 13q12-q13, 13q14 and 13q31-q34. LOH at
      chromosome 13q12-q13 was associated with low progesterone receptor content, a
      high S phase fraction and aneuploidy. Multivariate analysis adjusting for lymph
      node involvement and S phase fraction showed that patients with tumours
      exhibiting LOH at 13q12-q13 have a 3-4-fold increased risk of recurrence and
      death compared with other patients. Our results suggest there are at least three
      separate LOH target regions at chromosome 13q and inactivation of one or more
      genes at chromosome 13q12-q13 results in poor prognosis for breast cancer
      patients.

PMID- 10070315
TI  - Telomerase activity and human papillomavirus (HPV) infection in human uterine
      cervical cancers and cervical smears.
AB  - Telomerase activity and human papillomavirus (HPV) infection were investigated in
      uterine cervical samples using molecular biology techniques. Thirteen cervical
      carcinomas and corresponding normal tissue from the same patient, and 102
      cervical swabs were examined. Telomerase activity was detected in 12 of 13
      cervical cancer tissues (92%). Of the 12 cases that showed telomerase activity,
      all were HPV positive, and the one case that did not show telomerase activity was
      HPV negative. A telomeric repeat amplification protocol assay detected telomerase
      activity in one out of seven normal cervical tissues (14%), and this one case was
      HPV positive. In cervical smear samples, telomerase activity was detected in two
      out of 36 normal smears (6%; both HPV positive), in 10 of 32 (31%) CIN1 (cervical
      intra-epithelial neoplasia) cases (three HPV positive), in four of five (80%)
      CIN2 cases (two HPV positive), in 15 of 21 (71%) CIN3 cases, (seven HPV positive)
      and in seven of eight (88%) squamous cell carcinoma cases (six HPV positive).
      These results suggest that telomerase activity may play some role in cervical
      carcinogenesis, and telomerase activity is associated with HPV infection in
      uterine cervical lesions.

PMID- 10070316
TI  - Detection of SYT-SSX1/2 fusion transcripts by reverse transcriptase-polymerase
      chain reaction (RT-PCR) is a valuable diagnostic tool in synovial sarcoma.
AB  - Cytogenetically, most synovial sarcomas are characterised by a specific
      chromosomal translocation [(X;18) (p11.2;q11.2)], which results in the generation
      of fusion transcripts comprising SYT (18q11) and either SSX1 or SSX2 (Xp11)
      sequences. By using a sensitive reverse transcriptase-polymerase chain reaction
      (RT-PCR) protocol, specific SYT-SSX1/2 fusion transcripts were detected in 10
      histopathologically confirmed synovial sarcomas. Control tumours with
      morphological spindle cell patterns mimicking monophasic synovial sarcoma tested
      negative (18/19) in the RT-PCR protocol, with the exception of one spindle cell
      sarcoma originally classified as a fibrosarcoma. Furthermore, the established RT
      PCR protocol was used to evaluate the feasibility of SYT-SSX1/2 fusion transcript
      detection for minimal residual disease analysis. Analyses of surgical margins
      revealed a fusion transcript in two of four operations for synovial sarcoma
      analysed, one of which was diagnosed with tumour free margins by conventional
      histopathology. These data suggest that the RT-PCR amplification of SYT-SSX1/2
      fusion transcripts is a valuable tool in the differentiation of synovial
      sarcomas, especially in cases of equivocal morphology. Additionally, the RT-PCR
      approach may be used for the detection of residual tumour cells in synovial
      sarcoma patients.

PMID- 10070317
TI  - Human malignant fibrous histiocytomas in vitro: growth characteristics and their
      association with expression of mRNA for platelet-derived growth factor,
      transforming growth factor-alpha and their receptors.
AB  - Eight human malignant fibrous histiocytomas were examined in vitro, in order to
      relate their growth properties to mRNA expression for platelet-derived growth
      factor (PDGF), PDGF receptor (PDGF-R), transforming growth factor-alpha (TGF
      alpha) and the epidermal growth factor receptor (EGF-R). Reverse transcriptase
      polymerase chain reaction (RT-PCR) showed that all cell lines expressed mRNA for
      PDGF-R alpha and/or PDGF-R beta; six cell lines expressed mRNA for the PDGF-A
      chain, with one cell line coexpressing PDGF-B chain mRNA; seven cell lines
      expressed mRNA for TGF-alpha whereas six cell lines expressed EGF-R mRNA.
      Conditioned medium from three cell lines contained PDGF; none of the cell lines
      released TGF-alpha. Two cell lines grew without serum requirements; whereas both
      expressed mRNA for PDGF, PDGF-R, TGF-alpha and EGF-R, other cell lines, unable to
      grow without serum, showed the same combination of growth factor/growth factor
      receptor expression. The two cell lines able to grow without serum were also
      shown to be stimulated by the addition of PDGF-BB. These findings show that
      simultaneous expression of mRNA for a growth factor and its receptor does not
      necessarily imply an autocrine or paracrine loop. However, two of our cell lines
      fulfil the requirements of possible PDGF-related autocrine and paracrine
      regulation.

PMID- 10070318
TI  - Protamine inhibits angiogenesis and growth of C6 rat glioma; a synergistic effect
      when combined with carmustine.
AB  - Protamine inhibits angiogenesis and blocks endothelial, fibroblast and platelet
      growth factors. Human and experimental gliomas spread and grow in response to
      both paracrine and autocrine release of these factors. Our objective was to study
      the effect of protamine administration on cell proliferation, angiogenesis and
      tumoral growth of C6 glioma. Additionally, we compared the antitumoral effect of
      protamine with that of another inhibitor of angiogenesis, suramin, and
      investigated a potential synergistic antitumoral action of low doses of protamine
      combined with the antineoplastic carmustine. C6 glioma cells were implanted
      subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of
      animals; when the tumour reached a diameter of 1.5 cm, either protamine, suramin,
      carmustine or protamine plus carmustine were administered in various doses.
      Tumour parameters were measured and compared between groups. In a dose-dependent
      manner, protamine reduced tumour volume (P < 0.001), mitotic index (P < 0.05),
      vascular density (P < 0.05) and cell viability (P < 0.005) of C6 glioma. An
      ultrastructural study demonstrated membranous inclusions in the cytoplasm of 28%
      of tumoral and endothelial cells of tumours from animals treated with protamine.
      The inhibition of tumoral growth produced by moderate doses of protamine was
      similar to that produced by toxic doses of suramin. The combination of protamine
      and carmustine had a synergistic curtailing effect on tumoral growth (P < 0.001).
      Our results indicate that protamine is an effective agent against glioblastoma;
      in non-toxic doses it could potentiate the antineoplastic effect of nitrosoureas
      for the treatment of glial tumours.

PMID- 10070319
TI  - CD44 exon v6 correlates with cellular differentiation but not with progression
      and metastasis of cervical cancer.
AB  - The purpose of this study was to investigate whether CD44v6 expression correlates
      with progression or metastasis of cervical cancer. The presence of mRNA for
      CD44v6 was examined, the association with clinicopathological features was
      assessed in 80 patients with cervical cancer by reverse transcriptase-polymerase
      chain reaction (RT-PCR) and subsequent Southern blot hybridisation with an
      oligonucleotide probe specific for v6. The standard form of CD44 was expressed in
      all specimens and 53 of 80 cervical cancers expressed an isoform containing exon
      v6 in combination with other variant exons. In addition, longer size transcripts
      of more than 1350 bp (long form) were identified in 22 of the 53 CD44v6 positive
      patients. The expression of CD44v6 and CD44v6 long form in squamous cell
      carcinomas was significantly higher than that in non-squamous cell carcinomas (P
      < 0.001). The expression of CD44v6 long form in histological grade 1 and 2 was
      significantly higher than that in grade 3 (P < 0.05). 47 patients in stage Ib-IIb
      cervical cancers were treated by radical hysterectomy and pelvic lymphadenectomy.
      We did not find any association between the expression of the long form or the
      short form of CD44v6 and any pathological features, except for histological cell
      type. These findings suggest that the regulation of CD44v6 seems to be different
      between different histological cell types and different tumour grades, and the
      expression of CD44v6 might not be implicated in the progression and metastasis of
      cervical cancer.

PMID- 10070320
TI  - Genomic aberrations in renal cell carcinomas detected by restriction landmark
      genomic scanning.
AB  - In order to reveal and characterise genetic events occurring in renal
      tumorigenesis, samples of sporadic renal cell carcinomas (RCCs) were examined
      using restriction landmark genomic scanning (RLGS), an electrophoretic separation
      technique which detects gene amplification and deletion. We were able to find two
      fragments frequently amplified and 10 others commonly showing reduced signal
      intensity within the 16 tumour samples analysed. These altered spots were located
      on chromosomes 2, 3, 9-12, 16, 17 and 18 according to chromosomal assigned RLGS.
      A subset of reduced fragments appeared to be correlated to tumour type and were
      located within a new chromosomal region, suggesting genetic specificity within
      the process of renal carcinogenesis.

PMID- 10070321
TI  - Growth regulation of human colon cancer cells by epidermal growth factor and 1,25
      dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression.
AB  - The human colon adenocarcinoma-derived cell line Caco-2 was used as a model
      system to study the interaction of epidermal growth factors (EGF) and 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) in control of colorectal cancer cell growth.
      The mitogenic stimulus of EGF was rapidly transduced via apical and basal
      membrane receptors alike into elevation of c-myc expression, causing a shift of
      Caco-2 cells from the G0/G1 into the S phase of the cell cycle. The stimulatory
      effect of EGF on cell division was effectively counteracted by 1,25(OH)2D3: the
      presence of the steroid hormone prevents the negative effect of EGF on vitamin D
      receptor abundance and concurrently minimises ligand-occupied EGF receptor
      numbers on both sides of Caco-2 cell monolayers. Our data suggest that EGF and
      1,25-(OH)2D3 actions on mutual receptor levels represent a specific feature of
      the potent antimitogenic effect of the steroid hormone on colon cancer cells.

PMID- 10070322
TI  - Cisplatin, doxorubicin and etoposide (PAV) in advanced gastric carcinoma: the
      SAKK experience. Swiss Group for Clinical Cancer Research (SAKK).
AB  - EAP (etoposide, doxorubicin, cisplatin), a chemotherapeutic combination given
      over 8 days, proposed by German investigators in cancer of the stomach, has been
      considered to be too toxic by others. A positive experience with a similar
      regimen (PAV) developed by the SAKK given over 3 days in small cell lung cancer
      led us to test it in gastric adenocarcinoma. 41 patients with metastatic gastric
      cancer were enrolled in the study and 38 were evaluable for response and
      toxicity. One complete response and 12 partial responses were recorded, giving a
      response rate of 34% (95% confidence interval (CI) 20-51%). Median progression
      free and overall survival were 3.4 and 6.3 months, respectively. Haematotoxicity
      was the leading toxicity with 34 (90%) and 17 (45%) grade III-IV neutropenia and
      thrombocytopenia, respectively. Despite this high rate of granulocytopenia, only
      six episodes of non-fatal febrile neutropenia were observed. Other toxicities
      were relatively easy to manage with infrequent grade III-IV occurrences. We
      conclude that PAV is active in gastric cancer and seems to be better tolerated
      than EAP.

PMID- 10070324
TI  - Comments on: Why do patients with weight loss have a worse outcome when
      undergoing chemotherapy for gastrointestinal malignancies, Andreyev et al., Eur J
      Cancer 1998, 34, pp. 503-509.

PMID- 10070323
TI  - Treatment of metastatic malignant melanoma with dacarbazine plus fotemustine.
AB  - Despite the poor prognosis of metastatic malignant melanoma, polychemotherapy
      with dacarbazine and fotemustine has shown promising results in several studies.
      We report on the clinical efficacy of a new sequential administration regimen
      with dacarbazine at a dose of 200 mg/m2 followed 24 h later by fotemustine 100
      mg/m2 every 4 weeks in 63 patients with metastatic melanoma. A complete response
      was noted in 3 patients (5%), a partial response in 4 patients (6%), stable
      disease in 33 patients (5%) and progressive disease in 23 patients (37%). The
      duration of the 3 complete responses was 5, 14+ and 60+ months, for the 4 partial
      responses, 3, 4, 6 and 13 months. The median duration for stable disease was 4
      months. The best response rates were obtained for lung and lymph node metastases.
      Toxicity was mild and mainly limited to haematological without pulmonary side
      effects. Although there was a relatively low objective response rate, this
      chemotherapy regimen as a palliative treatment, is potentially valuable for
      patients with progressive stage IV melanoma.

PMID- 10070325
TI  - Double modulation of 5-fluorouracil with interferon alpha-2a and high-dose
      leucovorin in advanced neuroendocrine tumours.

PMID- 10070326
TI  - Anti-HER-2/neu antibodies detected in sera of patients with breast cancer, but
      also in healthy females.

PMID- 10070327
TI  - Fine needle aspiration of lymph nodes.

PMID- 10070328
TI  - Detection of small numbers of immature cells in the blood of healthy subjects.
AB  - AIMS: To determine the frequency of immature haemopoietic cells in the peripheral
      blood of healthy persons. METHODS: Cytocentrifuge preparations were made using
      mononuclear leucocytes separated by a Ficoll-Hypaque density gradient. The slides
      were stained by May-Grunwald-Giemsa. The combination with immunoperoxidase
      technique allowed immunotyping of uncommon blood cells. RESULTS: Blast cells
      expressing the progenitor cell marker CD34 represented 0.11 (0.06) per cent (mean
      (SD)) of the total mononuclear leucocyte count; these were the haemopoietic
      progenitor cells in the peripheral blood. Dark blue cells expressing CD38, CD45,
      HLA-DR, CD4, CD11a, CD29, CD49d, CD50, and CD54 represented 0.30 (0.21) per cent
      of the mononuclear leucocytes; most of these cells did not express T, B, NK,
      myelomonocytic, progenitor cell, proliferation, activation, blood dendritic cell,
      or follicular dendritic cell markers. These were dendritic cell precursors in the
      peripheral blood. Very small numbers of cells expressing CD83 were found. Blast
      like cells expressing CD45, HLA-DR, CD11a, and CD50 represented 0.15 (0.10) per
      cent of the mononuclear leucocytes; morphology and immunotyping supported the
      conclusion that these cells were poorly differentiated monocytes. CONCLUSIONS:
      Morphological investigation of mononuclear leucocytes in peripheral blood of
      healthy persons can be used to detect small numbers of blasts, dark blue cells,
      and blast-like cells. The immunoperoxidase technique can then be used for
      immunotyping of these cells. This simple method may be helpful in diagnosing
      haematological disorders.

PMID- 10070329
TI  - The expression of beta-catenin in non-small-cell lung cancer: a
      clinicopathological study.
AB  - AIMS: To investigate the expression of beta-catenin in non-small-cell lung cancer
      (NSCLC) and its clinical significance. METHODS: 101 patients were surgically
      treated for NSCLC by lobectomy or pneumectomy with systematic lymph node
      dissection. Follow up was available in all patients, ranging from 24 to 110
      months. Immunostaining of tissue sections from primary tumours and (when present)
      their lymph node metastases was performed and evaluated using a monoclonal
      antibody against beta-catenin. Correlations were investigated between beta
      catenin immunostaining in primary tumours and E-cadherin immunostaining (data
      available from a previous study), lymph node stage, and survival. RESULTS: There
      were significant correlations between scores for beta-catenin immunostaining and
      E-cadherin immunostaining in primary tumours (p = 0.007), and between the beta
      catenin immunostaining score in primary tumours and in their lymph node
      metastases (p = 0.006). An inverse correlation was found between the beta-catenin
      immunostaining score in primary tumours and lymph node stage N0, N1, or N2 (p =
      0.03). According to the Kaplan-Meier survival estimate, the level of beta-catenin
      expression in primary tumours was a statistically significant prognostic factor
      (p = 0.01). CONCLUSIONS: Reduced beta-catenin expression in surgically treated
      NSCLC is clearly associated with lymph node metastasis and an infavourable
      prognosis. The existence of a functional relation between E-cadherin and beta
      catenin is supported by the results of this clinicopathological study.

PMID- 10070330
TI  - Quantitative assessment of gastric atrophy using the syntactic structure
      analysis.
AB  - AIM: To assess the topographical relation between gastric glands, using the
      minimum spanning tree (MST), to derive both a model of neighbourhood and
      quantitative representation of the tissue's architecture, to assess the
      characteristic features of gastric atrophy, and to assess the grades of gastric
      atrophy. METHODS: Haematoxylin and eosin stained sections from corporal and
      antral biopsy specimens (n = 139) from normal patients and from patients with
      nonatrophic gastritis and atrophic gastritis of grades 1, 2, and 3 (Sydney
      system) were assessed by image analysis system (Prodit 5.2) and 11 syntactic
      structure features were derived. These included both line and connectivity
      features. RESULTS: Syntactic structure analysis was correlated with the
      semiquantitative grading system of gastric atrophy. The study showed significant
      reductions in the number of points and the length of MST in both body and antrum.
      The standard deviation of the length of MST was significantly increased in all
      grades of atrophy. The connectivity to two glands was the highest and most
      affected by the increased grade of atrophy. The reciprocal values of the Wiener,
      Randic, and Balaban indices showed significant changes in the volume of gland,
      abnormality in the shape of glands, and changes in irregularity and branching of
      the glands in both types of gastric mucosa. There was a complete separation in
      the MST, connectivity, and index values between low grade and high grade gastric
      atrophy. CONCLUSIONS: (1) Gastric atrophy was characterised by loss of the gland,
      variation in the volume, reduction in the neighbourhood, irregularity in spacing,
      and abnormality in the shape of the glands. (2) Syntactic structure analysis
      significantly differentiated minor changes in gastric gland (low grade atrophy)
      from high grade atrophy of clinical significance. (3) Syntactic structure
      analysis is a simple, fast, and highly reproducible technique and appears a
      promising method for quantitative assessment of atrophy.

PMID- 10070331
TI  - Progression from colorectal adenoma to carcinoma is associated with non-random
      chromosomal gains as detected by comparative genomic hybridisation.
AB  - AIMS: Chromosomal gains and losses were surveyed by comparative genomic
      hybridisation (CGH) in a series of colorectal adenomas and carcinomas, in search
      of high risk genomic changes involved in colorectal carcinogenesis. METHODS: Nine
      colorectal adenomas and 14 carcinomas were analysed by CGH, and DNA ploidy was
      assessed with both flow and image cytometry. RESULTS: In the nine adenomas
      analysed, an average of 6.6 (range 1 to 11) chromosomal aberrations were
      identified. In the 14 carcinomas an average of 11.9 (range 5 to 17) events were
      found per tumour. In the adenomas the number of gains and losses was in balance
      (3.6 v 3.0) while in carcinomas gains occurred more often than losses (8.2 v
      3.7). Frequent gains involved 13q, 7p, 8q, and 20q, whereas losses most often
      occurred at 18q, 4q, and 8p. Gains of 13q, 8q, and 20q, and loss of 18q occurred
      more often in carcinomas than in adenomas (p = 0.005, p = 0.05, p = 0.05, and p =
      0.02, respectively). Aneuploid tumours showed more gains than losses (mean 9.3 v
      4.9, p = 0.02), in contrast to diploid tumours where gains and losses were nearly
      balanced (mean 3.1 v 4.1, p = 0.5). CONCLUSIONS: The most striking difference
      between chromosomal aberrations in colorectal adenomas and carcinomas, as
      detected by CGH, is an increased number of chromosomal gains that show a
      nonrandom distribution. Gains of 13q and also of 20q and 8q seem especially to be
      involved in the progression of adenomas to carcinomas, possibly owing to low
      level overexpression of oncogenes at these loci.

PMID- 10070332
TI  - An assessment of the operation of an external quality assessment (EQA) scheme in
      histopathology in the South Thames (West) region: 1995-1998.
AB  - AIMS: To describe the design and organisation of a voluntary regional external
      quality assessment (EQA) scheme in histopathology, and to record the results
      obtained over a three year period. METHODS: A protocol is presented in which
      circulation of EQA slides alternated with teaching sessions. Procedures for the
      choice of suitable cases, evaluation of submitted diagnoses, and feedback of
      results to participants are described. The use of teaching sessions,
      complementary to the slide circulations, and dealing with current diagnostic
      problems is also outlined. RESULTS: Participation rates in the nine slide
      circulations varied between 66% and 89%, mean 85%. Overall scores were
      predictably high but 4% of returns, from 10 pathologists, were unsatisfactory.
      These low scores were typically isolated or intermittent and none of the
      participants fulfilled agreed criteria for chronic poor performers. CONCLUSIONS:
      This scheme has been well supported and overall performances have been
      satisfactory. The design was sufficiently discriminatory to reveal a few low
      scores which are analysed in detail. Prompt feedback of results to participants
      with identification of all "incomplete" and "wrong" diagnoses is essential.
      Involvement of local histopathologists in designing, running, and monitoring such
      schemes is important.

PMID- 10070334
TI  - A rapid polymerase chain reaction technique for detecting M tuberculosis in a
      variety of clinical specimens.
AB  - A rapid in-house polymerase chain reaction (PCR) assay is described for the
      direct detection of Mycobacterium tuberculosis complex in clinical material. Its
      performance is compared with two kit based systems. The results of the in-house
      assay were comparable with the commercial assays, detecting M tuberculosis in
      100% of smear positive, culture positive samples. The in-house assay proved to be
      rapid, easy, and inexpensive to perform, and the inclusion of an internal
      inhibitor control permitted validation of the PCR results.

PMID- 10070333
TI  - Qualitative and semiquantitative polymerase chain reaction testing for
      cytomegalovirus DNA in serum allows prediction of CMV related disease in liver
      transplant recipients.
AB  - AIM: To identify cytomegalovirus (CMV) infection in liver transplant recipients
      by polymerase chain reaction (PCR) techniques and to separate the cases in which
      CMV related disease will occur, for whom treatment is indicated, from those in
      whom infection will remain innocuous. METHODS: The combination of qualitative and
      semiquantitative PCR of serum and urine was assessed to determine whether these
      assays can identify those at risk of CMV related disease and compared their
      performance with conventional approaches to diagnosis. RESULTS: Qualitative PCR
      of serum had superior specificity, sensitivity, and positive and negative
      predictive values compared with urine DEAFF (detection of early antigen
      fluorescent foci) and PCR of urine. All episodes of CMV related disease were
      associated with the presence of CMV DNA by PCR in serum or urine; CMV was
      detected before clinical onset in 70% and 60% of cases, respectively. The period
      over which CMV DNA could be detected was not correlated with CMV related disease.
      Both peak viral load and cumulative viral load estimated using a semiquantitative
      PCR method on serum samples positive by the qualitative method could be used to
      distinguish asymptomatic infection from CMV related disease with 100% specificity
      and sensitivity. In contrast semiquantitative PCR of urine was of little value.
      CONCLUSIONS: An approach based on PCR testing with a combination of qualitative
      and subsequently semiquantitative serum samples would improve the diagnosis of
      CMV infection and aid identification of those patients at risk of CMV related
      disease, allowing treatment to be targeted specifically.

PMID- 10070335
TI  - Atypical mycobacterial lymphadenitis in childhood--a clinicopathological study of
      17 cases.
AB  - AIMS: To assess the clinical and pathological features of atypical mycobacterial
      lymphadenitis in childhood to define the salient clinical and histological
      features. METHODS: 17 cases were included on the basis of positive culture or
      demonstration of bacilli of appropriate morphology and staining characteristics.
      RESULTS: The mean age at diagnosis was 4.86 years. All children were systemically
      well, with clear chest x rays. Unilateral cervical lymphadenopathy was the
      commonest mode of presentation. Differential Mantoux testing played no part in
      diagnosis. Clinical diagnosis improved with awareness. Treatment varied with
      surgeons opting for excision and paediatricians adding six months antituberculous
      chemotherapy. Acid- and alcohol-fast bacilli were identified in nine cases.
      Bacterial cultures were conducted in 16 cases and were positive for atypical or
      nontuberculous mycobacteria in 14, the main organism being M avium-intracellulare
      complex (11 cases). Histologically, 12 cases had bright eosinophilic serpiginous
      necrosis with nuclear debris scattered throughout the necrotic foci. Langhans
      type giant cells featured in the majority of cases but infiltration by plasma
      cells and neutrophils was not consistent. CONCLUSIONS: Atypical mycobacterial
      lymphadenitis of childhood represents a rare but significant disease with
      characteristic clinical and histological features.

PMID- 10070336
TI  - Vaginal epithelioid angiosarcoma.
AB  - A case of epithelioid angiosarcoma of the vagina is described. Only five cases of
      angiosarcoma at this site have been reported, three of which followed
      radiotherapy for other gynaecological malignancies. None is described as an
      epithelioid angiosarcoma, an unusual and recently described variant which is
      readily confused with carcinoma. This is thought to be the first reported
      epithelioid angiosarcoma at this site and highlights the difficulties in
      diagnosis.

PMID- 10070337
TI  - Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case
      report.
AB  - An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented
      as a pituitary tumour in a young adult Chinese female, who subsequently died
      after having undergone trans-sphenoidal resection. Metastatic cancers of the
      pituitary are uncommon even in necropsy series and rarely give rise to clinical
      symptoms. This case draws attention to the fact that, although uncommon,
      pituitary metastases have been noted with increasing frequency and their
      distinction from primary pituitary tumours is often difficult. A metastatic
      pituitary tumour may be the initial presentation of an unknown primary
      malignancy, wherein the metastatic deposits may also be limited to the pituitary
      gland. Clinicians and pathologists alike should consider a metastatic lesion in
      the differential diagnosis of a non-functioning pituitary tumour.

PMID- 10070338
TI  - Breast carcinoma developing in patients on hormone replacement therapy: a
      histological and immunohistological study.
AB  - AIM: To study the histopathological features of breast carcinoma developing in
      postmenopausal patients on hormone replacement therapy (HRT). METHODS: The sample
      comprised 60 patients with invasive breast carcinoma including 31 who had
      received HRT at or shortly before presentation, and 29 who had not. Details
      concerning their tumour size, histological type and grade, lymph node status, and
      oestrogen and progesterone receptor status were compared. Immunoperoxidase
      staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of
      all 60 patients. The results were then statistically analysed. RESULTS: Tumours
      detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p =
      0.0156) and of a lower histological grade (p = 0.0414) than those detected in non
      HRT patients. The incidence of invasive lobular carcinoma was slightly higher in
      HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2
      positive (compared with 79% in the control group), 29% were p53 positive (45% in
      the control), and 48% were E-cadherin positive (72% in the control group).
      Although the differences were not statistically significant there was a trend
      towards higher incidence of p53 negative and E-cadherin negative tumours in HRT
      patients. CONCLUSIONS: Breast carcinomas detected in patients on HRT have a
      significantly higher incidence of two favourable prognostic features (small size
      and a low histological grade). They also show a trend, statistically not
      significant, of being p53 negative and E-cadherin negative; this may be related
      to the slightly higher incidence of invasive lobular tumours in these patients.

PMID- 10070339
TI  - Primary yolk sac tumour of the liver in adulthood.
AB  - Primary yolk sac tumour of the liver is exceedingly rare. A 28 year old woman
      presented with a cystic liver mass and a markedly raised serum alpha-fetoprotein
      concentration. She underwent a partial hepatectomy for a suspected hepatocellular
      carcinoma but histological examination of the tumour revealed the classical
      morphological and immunohistochemical features of a yolk sac tumour. There was no
      evidence of an extrahepatic primary source. Review of this case, together with
      the six previously reported adult cases of primary yolk sac tumours of the liver,
      revealed several features of the tumour that may aid differentiation from
      hepatocellular carcinoma, with potential therapeutic implications.

PMID- 10070340
TI  - Thorotrast associated nodular regenerative hyperplasia of the liver.
AB  - A case of nodular regenerative hyperplasia (NRH) of the liver is described in
      association with exposure to the radiographic contrast medium Thorotrast. This is
      the first case in which the pathological findings have been fully documented. It
      is suggested that NRH may have developed through Thorotrast induced damage to
      portal vein radicles.

PMID- 10070341
TI  - Vitamin K and metabolic bone disease.

PMID- 10070342
TI  - Variability of immunohistochemical reactivity on stored paraffin slides.

PMID- 10070343
TI  - Sudden infant death syndrome, long QT interval, and Helicobacter pylori.

PMID- 10070344
TI  - Epithelial-myoepithelial carcinoma?

PMID- 10070345
TI  - Is the practice of haematology evidence based?

PMID- 10070346
TI  - The Parkes Lecture. Heat and the testis.
AB  - The evidence for the lower temperature of the testes of many mammals is
      summarized, and the reasons suggested for the descent of the testes into a
      scrotum are discussed. Descriptions are given of the various techniques used for
      studying the effects of heat on the testis, whole body heating, local heating of
      the testes (by inducing cryptorchidism, scrotal insulation or immersion of the
      scrotum in a water bath), and heating of tissue or cell preparations in vitro.
      The effects of heat are discussed, effects on the testis (weight, histology,
      physiology, biochemistry and endocrinology), on the numbers and motility of
      spermatozoa in rete testis fluid and semen, on fertilizing ability of spermatozoa
      and on the subsequent development of the embryos produced when spermatozoa from
      heated testes are used to fertilize normal ova. The possible mechanisms for the
      damaging effects of heat are discussed, as well as the importance of heat-induced
      abnormalities in male reproduction in domestic animals and humans.

PMID- 10070347
TI  - Characterization of uterine leukocyte infiltration in gilts after artificial
      insemination.
AB  - The objective of this study was to characterize the uterine leukocyte influx
      after artificial insemination (AI). After detection of oestrus with a boar at
      intervals of 1.5 h, seventy-two gilts were randomly assigned to a 2 x 3 x 4
      factorial arrangement. AI was performed with 100 ml extended semen containing 5 x
      10(9) spermatozoa (semen; n = 36) or 100 ml VSP semen extender (extender; n = 36)
      at one of three times after detection of oestrus: 12, 24 or 36 h (n = 24/time).
      The uterus was lavaged at 6, 12, 18 or 24 h (n = 18/time) after AI to determine
      the total number of uterine leukocytes. In addition, uterine lavage was performed
      on nine untreated gilts immediately after the detection of oestrus to establish a
      baseline number of leukocytes. The leukocyte response in all samples consisted
      predominately (92-99%) of polymorphonuclear neutrophilic granulocytes (PMNs). The
      mean number of PMNs recovered from the uteri of gilts treated with semen was
      greater than in gilts treated with extender and in untreated gilts (P < 0.01).
      The greatest number of PMNs in semen-treated gilts was found 12 h after AI (P <
      0.01), and this number was sustained for 24 h. In contrast, the number of uterine
      PMNs recovered from extender-treated gilts reached a peak at 6 h and had declined
      by 12 h after AI (P < 0.05). It was concluded that an extensive influx of PMNs
      into the uterus is a normal sequence to AI. The consequences and importance of
      semen-induced uterine leukocytosis needs further investigation.

PMID- 10070348
TI  - Control of luteolysis in the one-humped camel (Camelus dromedarius).
AB  - Blood plasma concentrations of 13,14-dihydro-15-keto PGF2 alpha (PGFM) were
      measured in groups of mature non-pregnant and pregnant camels to study PGF2 alpha
      release patterns around the time of luteolysis and the timing of the signal for
      pregnancy recognition. Injection of each of four camels with 10 and 50 mg of PGF2
      alpha showed clearly that five times the dose of exogenous hormone produced five
      times the amount of PGFM in peripheral plasma, thereby indicating that, as in
      other animal species, PGFM is the principal metabolite of PGF2 alpha in the
      camel. Serial sampling of three non-pregnant camels on each of days 8, 10 and 12,
      and three pregnant camels on day 10, after ovulation for 8 h showed a significant
      (P < 0.05) rise in mean plasma PGFM concentrations only on day 10 in the non
      pregnant, but not the pregnant, animals. A single intravenous injection of 20, 50
      or 100 iu oxytocin given to three groups of three non-pregnant camels on day 10
      after ovulation did not increase their basal serum PGFM concentrations. However,
      daily treatment of six non-pregnant camels between days 6 and 15 (n = 3) or 20 (n
      = 3) after ovulation with 1-2 g of the prostaglandin synthetase inhibitor,
      meclofenamic acid, inhibited PGF2 alpha release and thereby resulted in continued
      progesterone secretion throughout the period of meclofenamic acid administration.
      These results showed that, as in other large domestic animal species, release of
      PGF2 alpha from, presumably, the endometrium controls luteolysis in the dromedary
      camel. Furthermore, reduction in the amount of PGF2 alpha released is associated
      with luteal maintenance and the embryonic signal for maternal recognition of
      pregnancy must be transmitted before day 10 after ovulation if luteostasis is to
      be achieved. However, the results also indicate that, in contrast to ruminants,
      the release of endometrial PGF2 alpha in the non-pregnant camel may not be
      controlled by the release of oxytocin.

PMID- 10070349
TI  - Distribution of 5-chloromethylfluorescein diacetate staining during meiotic
      maturation and fertilization in vitro of mouse oocytes.
AB  - The aim of this confocal microscopy study was to determine whether the pattern of
      CellTracker Green 5-chloromethylfluorescein diacetate (CMFDA) staining changes
      during meiotic maturation and fertilization in vitro of mouse oocytes. At
      different times during meiotic maturation and fertilization, oocytes, zygotes and
      two-cell embryos were stained with CMFDA to demonstrate intracellular glutathione
      S-transferase activity. After washing in CMFDA-free medium, most oocytes, zygotes
      and embryos were stained with dihydroethidium (HE) to visualize DNA structures.
      Meiotic maturation and fertilization in vitro of mouse oocytes were associated
      with changes in the pattern of intracellular CMFDA staining. In particular,
      accumulations of CMFDA-positive membranes were observed around the nucleus of
      germinal vesicle (GV) oocytes, overlaying the sperm nucleus as well as overlaying
      the first mitotic spindle if this approached the plasma membrane. Staining of
      oocytes and zygotes with the probes 3,3'-dihexyloxacarbocyanine iodine
      [DiOC6(3)], which stains all the intracellular membranes, and rhodamine 123,
      which stains active mitochondria, demonstrated that the intracellular structures
      evidenced by CMFDA staining did not correspond to accumulations of mitochondria.
      Exposure of oocytes and zygotes to the microtubule-disrupting agent nocodazole or
      the actin-depolymerizing drug cytochalasin D revealed an autonomous microfilament
      dependent transport and relocation of CMFDA-positive membranes during meiotic
      maturation and fertilization. Such a transport of CMFDA-positive membranes may be
      envisaged as a protective shield built to prevent damage to DNA from endogenous
      and exogenous mutagen metabolites.

PMID- 10070350
TI  - A new tool for measuring the suckling stimulus during breastfeeding in humans:
      the orokinetogram and the Fourier series.
AB  - The Fourier series was used to analyse the oral movements recorded by the
      orokinetogram during breastfeeding in human babies. This is a new method that
      allows recording of oral movements without introducing any extrinsic element
      between the nipple and the mouth of the baby. The advantage of displaying
      suckling activity after fast Fourier transform (FFT) is that this algorithm
      allows storage, quantification and frequency analysis of the oral movements
      throughout a suckling bout, which enables the total oral activity to be measured.
      Two types of oral movements are found: slow high amplitude (SHA) and fast low
      amplitude (FLA). FLA movements may be derived from peristaltic movements of the
      tongue that result in tickling stimuli to the mechanoreceptors of the nipple and
      milk expression. The frequency bandwidth of oral movements is wider (0-8 Hz) than
      has been described previously (0-3 Hz) and this is due to the presence of the FLA
      oral movements. An indirect measurement of the energy of oral movements during
      suckling is obtained by the pattern of energy distribution used in each
      individual frequency band by oral movements. This pattern changes in relation to
      the periods of continuous and intermittent suckling activity. SHA and FLA oral
      movements are more intense during continuous suckling. Statistical analysis
      showed a correlation between the energy of SHA and FLA waves throughout the
      suckling bout, and also that the highest level of energy during suckling activity
      is displayed during the first 2 min. The novel tools described in this paper
      allow investigation of the role of suckling stimulus in reflex hormone release
      and other mother-infant interactions.

PMID- 10070351
TI  - Effects of taurine on the motility and intracellular free Ca2+ concentration of
      fowl spermatozoa in vitro.
AB  - The effects of taurine on the motility and intracellular free Ca2+ concentration
      of fowl spermatozoa were investigated in vitro. The addition of taurine, within
      the range of 0-5 mmol l(-1), did not appreciably affect the motility of intact
      fowl spermatozoa. Motility remained almost negligible at 40 degrees C, while
      vigorous movement was observed at 25 degrees C. Even with the addition of Ca2+
      before the addition of taurine, neither stimulation nor inhibition of motility
      was observed compared with the control (no addition of taurine). Similar results
      were obtained by the addition of taurine and calyculin A, a specific inhibitor of
      protein phosphatases. There were no changes in intracellular free Ca2+
      concentrations, measured by a fluorescent Ca2+ indicator, fura-2, in taurine
      treated spermatozoa. These results suggest that taurine is not involved in the
      regulation of fowl sperm motility and metabolism by intracellular Ca2+
      mobilization in vitro.

PMID- 10070352
TI  - Phenotypic differences in the GnRH neuronal system of deer mice Peromyscus
      maniculatus under a natural short photoperiod.
AB  - The neural mechanisms by which short photoperiod induces gonadal regression among
      seasonally breeding mammals are not well understood. One hypothesis suggests that
      the proximate cause of seasonal gonadal regression is a photoperiod-induced
      modification in GnRH secretion. This hypothesis is indirectly supported by our
      recent findings using immunocytochemistry which identified specific photoperiod
      induced adjustments in the number and morphology of GnRH containing neurones
      between reproductively competent and reproductively regressed laboratory housed
      male deer mice. Herein, we report that the GnRH neuronal system is similarly
      affected in reproductively responsive and nonresponsive wild male deer mice
      Peromyscus maniculatus exposed to a natural short photoperiod. The distribution
      of immunoreactive (IR)-GnRH neurones was nearly identical in field caught animals
      and those housed under artificial photoperiod in the laboratory. Compared with
      reproductively nonresponsive males, reproductively responsive mice from the field
      population possessed a greater total number of IR-GnRH neurones, a greater number
      of IR-GnRH neurones within the lateral hypothalamus, and a greater proportion of
      bipolar IR-GnRH neurones. Each of these distributional and morphological
      characters was consistent with our findings in laboratory housed male deer mice
      exposed to an artificial short photoperiod. Taken together, these data underscore
      the validity of using an artificial photoperiod to evaluate seasonal adjustments
      in reproductive function in the laboratory.

PMID- 10070353
TI  - Occurrence of prostasome-like membrane vesicles in equine seminal plasma.
AB  - Equine seminal plasma was shown to contain membrane vesicles that are similar to
      the well characterized prostasomes in human seminal plasma. Determination of
      nucleoside and nucleotide concentrations of these particles have shown that ATP,
      ADP and adenosine are the main components of the nucleotidic pool. 5'
      nucleotidase, endopeptidase and dipeptidyl peptidase i.v. activities have been
      found on the surface of the particles. The interaction between these prostasome
      like vesicles and spermatozoa was demonstrated by electron micrograph scans which
      revealed the steps of a fusion-like process leading to mixing of the membranes.
      In addition, endopeptidase activity, a marker enzyme of these seminal vesicles
      that is normally absent from equine spermatozoa, was shown to be acquired by
      these cells after interaction with the vesicles. The addition of these vesicles
      to equine spermatozoa resulted in the modification of adenylate catabolism.
      Therefore, a role in stabilizing the energy charge of the spermatozoa thus
      allowing longer viability is proposed for these organelles.

PMID- 10070354
TI  - Evaluation of ZP2 domains of functional importance with antisera against
      synthetic ZP2 peptides.
AB  - The mouse zona pellucida protein ZP2 plays an important role in the process of
      fertilization by mediating secondary sperm binding to mammalian oocytes. ZP2
      primary structures are highly conserved as revealed by cDNA cloning. The aim of
      the study was to identify ZP2 domains of functional relevance. Antisera were
      raised against synthetic peptides that are either conserved in the structure of
      ZP2 from different mammalian species (AS ZP2-20) or present in the human ZP2 but
      not in the mouse ZP2 amino acid sequence (AS ZP2-26). Antibody binding to zona
      pellucida proteins was assessed by assaying the antisera with human hemizonae.
      Using human zonae pellucidae, we demonstrated that anti-ZP2 common antibodies and
      anti-ZP2 human peptide antibodies react with human zona pellucida antigens. For
      the first time, ZP2 domains of functional relevance for human sperm-oocyte
      interaction could be identified applying the competitive hemizona assay.
      Antiserum AS ZP2-20 significantly inhibited binding of spermatozoa to test
      hemizonae, whereas treatment of hemizonae with AS ZP2-26 did not influence sperm
      oocyte interaction. These results show that antibodies against synthetic ZP2
      peptides react with ZP2 protein and that AS ZP2-20 identifies a linear ZP2
      epitope that is of possible functional importance for sperm-oocyte interaction.

PMID- 10070355
TI  - The effects of age and sex steroids on the macrophage population in the ovary of
      the chicken, Gallus domesticus.
AB  - The role of macrophages in the function of the hen ovary has not yet been
      described, although these cells may be an important regulator of ovarian function
      in mammals. The aim of this study was to determine the changes in the frequency
      of macrophages during ageing and follicular atresia, and the effects of sex
      steroids on the macrophage population in the hen ovary. Cryostat sections of
      ovarian tissues of immature, young laying and old laying hens and those of
      immature hens treated with or without diethylstilboestrol (DES) or progesterone
      were immunostained for macrophage cells using mouse anti-chicken macrophage
      monoclonal antibody. Macrophages were observed under a light microscope and
      counted using a computer assisted image analyser. The frequency of macrophages in
      both the stroma and theca of primary follicles was significantly greater in young
      laying hens than in immature and old laying hens and these cells were more
      frequent in old laying hens than in immature hens (P < 0.01). Macrophages were
      more frequent in atretic follicles than in normal follicles (P < 0.01). The
      number of macrophages in both the stroma and theca of primary follicles of DES
      treated birds was significantly greater than in those of progesterone-treated and
      control birds (P < 0.01). Progesterone had no significant effect on the
      population of macrophages. These results suggest that macrophages in the ovary
      increase in association with sexual maturation of birds and atresia of follicles
      and decrease during ageing. Oestrogen may be one of the factors that affect the
      population of macrophages in the hen ovary.

PMID- 10070356
TI  - Reproductive experience and opioid regulation of luteinizing hormone release in
      female rats.
AB  - The objective of the present study was to determine whether reproductive
      experience that produces shifts in opioid regulation of prolactin secretion and
      behavioural functions also alters opioid regulation of LH during the oestrous
      cycle or lactation. In Expt 1 the effect of naloxone administration (i.v.) on LH
      was compared between age-matched, nulliparous and primiparous, catheterized
      female rats on dioestrus II. In Expt 2, the effects of multiple reproductive
      experiences on opiate control of LH were investigated using cyclic, nulliparous
      and multiparous (three litters) rats. In both experiments, no differences in
      naloxone-stimulated LH release were found between groups even though multiple
      reproductive experiences resulted in the prolongation of oestrous cyclicity. In
      Expt 3, day 8 lactating primiparous rats were administered 2, 5, 10 or 25 mg
      naloxone kg-1 i.v. The three lowest naloxone doses, but not the 25 mg kg-1 dose,
      significantly increased LH concentrations. The possible effects of prior
      reproductive experience on opioid control of LH during lactation were then
      investigated. Naloxone at 0.5 mg kg-1, but not at 2 mg kg-1 or 10 mg kg-1,
      stimulated a significantly greater rise in LH in multiparous (two litters) than
      in primiparous females. Overall, these data indicate that while modest
      differences were found in naloxone-induced LH responses between multiparous and
      primiparous animals during lactation, reproductive experience did not
      significantly alter opioid regulation of LH during subsequent oestrous cycles at
      the naloxone doses examined. Hence, the effects of reproductive experience on
      opioid regulation of LH are less pronounced than those previously found for
      opioid regulation of prolactin and behaviour.

PMID- 10070358
TI  - Galactosyltransferase, pyrophosphatase and phosphatase activities in luminal
      plasma of the cauda epididymidis and in the rete testis fluid of some mammals.
AB  - Galactosyltransferase activity was measured in the luminal plasma of the cauda
      epididymidis of mice, rats, rabbits, rams and boars, and in the rete testis fluid
      of rams and boars. The activities of nucleotide pyrophosphatase and alkaline
      phosphatase, which compete with galactosyltransferase for substrate, were also
      determined. In these species, galactosyltransferase activity in the luminal
      plasma of the cauda epididymidis was similar when the inhibitory effect of
      pyrophosphatase and phosphatase was minimized by assay conditions. However, under
      assay conditions that did not minimize the effect of these enzymes, the
      galactosyltransferase activities of these species were very different and were
      inversely correlated with the activities of pyrophosphatase and phosphatase. The
      ratio of galactosyltransferase activity to pyrophosphatase and phosphatase
      activity was much higher in the rete testis fluid than in the luminal plasma of
      the cauda epididymidis in both rams and boars. In rams, galactosyltransferase in
      the luminal plasma of the cauda epididymidis was more heat resistant than that in
      serum. These results suggest that there is a species difference in the
      availability of galactosyltransferase activity in the luminal plasma of the cauda
      epididymidis and that in some species, galactosyltransferase in the luminal fluid
      is unlikely to have any function. The results are also discussed with respect to
      the possible function of galactosyltransferase, pyrophosphatase and phosphatase
      in epididymal luminal plasma and rete testis fluid.

PMID- 10070357
TI  - Effect of long-term food restriction on pituitary sensitivity to cLHRH-I in
      broiler breeder females.
AB  - The effect of long-term food restriction on the sensitivity of the pituitary to
      exogenously administered chicken luteinizing hormone releasing hormone I (cLHRH
      I) was investigated in three groups of broiler breeder females fed ad libitum,
      fed a restricted quantity of food or fed a restricted quantity of food to obtain
      an intermediate body weight between those of the first two groups. At 16 weeks of
      age, basal FSH release was higher in ad libitum fed birds, culminating in ovarian
      development and subsequent oestradiol production by the small follicles. At this
      age, LH secretion was independent of ovarian feedback factors. In all groups,
      cLHRH-I was most active in releasing LH in intact and ovariectomized animals and,
      to a lesser extent, in releasing FSH in ovariectomized birds. At 39 weeks of age,
      basal FSH concentrations were similar among intact animals of all groups, whereas
      LH concentrations differed among groups, with higher values in the restricted
      birds. This food effect was enhanced in ovariectomized birds. Furthermore, the
      high response to cLHRH-I in the ovariectomized, restricted birds compared with
      the ad libitum, ovariectomized group suggests an improved sensitivity of the
      hypothalamic-pituitary axis. In conclusion, birds fed ad libitum showed the
      highest responsiveness to ovarian factors and to cLHRH-I in releasing FSH in the
      period before sexual maturity. No effect of amount of feeding could be observed
      for LH. However, during the egg laying period, LH release by cLHRH-I was highly
      dependent on amount of feeding and on ovarian feedback regulation. This finding
      indicates that the amount of feeding can modify the sensitivity of the pituitary
      to cLHRH-I, and possibly to gonadal hormones, during the laying period.

PMID- 10070359
TI  - Luteinization and proteolysis in ovarian follicles of Meishan and Large White
      gilts during the preovulatory period.
AB  - This experiment was conducted to determine why follicles luteinize faster in the
      Meishan breed than in the Large White breed of pig. Follicles were recovered
      during the late follicular phase from ovaries of both breeds before and after
      administration of hCG given to mimic the LH surge. First, the patterns of
      cholesterol transporters (high and low density lipoproteins: HDL and LDL) were
      compared. Cholesterol transporters detected in follicular fluid consisted of HDL
      only. Similar amounts of Apolipoprotein A-I were found in all samples. There was
      no obvious breed effect on minor lipoproteins found in the HDL-rich fraction, and
      this pattern was altered similarly by hCG in the two breeds. The LDL-rich samples
      of serum from both breeds contained similar amounts of protein. Second, three
      steroidogenic enzymes, adrenodoxin, 17 alpha-hydroxylase-lyase (P450(17) alpha)
      and 3 beta-hydroxysteroid-dehydrogenase (3 beta-HSD) were detected by
      immunohistochemistry and quantified by image analysis on sections of the two
      largest follicles. Before hCG treatment, theca interna cells demonstrated
      immunoreactivities for adrenodoxin (strong), P450(17) alpha and 3 beta-HSD (very
      strong), whereas granulosa cells displayed immunoreactivities for adrenodoxin
      only. After hCG treatment, the localization of the enzymes was unchanged but the
      staining intensity of adrenodoxin on granulosa cells and 3 beta-HSD on theca
      cells increased (P < 0.01 and P < 0.05, respectively). Breed effects were
      detected for the amounts of adrenodoxin in theca cells (Meishan > Large White; P
      < 0.05) and of 17 alpha-hydroxylase (Large White > Meishan, P < 0.01). Breed x
      treatment interactions were never detected. Finally, gelatinases, plasminogen
      activator, plasminogen activator inhibitor, tissue inhibitors of metalloproteases
      (TIMP-1 and TIMP-2) were visualized by direct or reverse zymography or western
      blotting. Whatever the stage relative to LH administration, follicular fluid from
      Large White gilts contained more TIMP-1, and TIMP-2 (P < 0.02 and P < 0.01,
      respectively). No breed effect was detected for the amounts of gelatinases and
      plasminogen activator inhibitor 1. However, for these parameters, a significant
      breed x time interaction was obvious, as the Meishan follicles had a greater
      response to hCG (P < 0.01). Since proteolysis plays a key role in the
      bioavailability of growth factors such as insulin-like growth factor 1,
      fibroblast growth factor and transforming growth factor beta, which have the
      ability to alter gonadotrophin-induced progesterone production in pigs, the
      differences observed in its control in the present study may explain, at least in
      part, the different patterns of luteinization observed in Meishan and Large White
      follicles.

PMID- 10070360
TI  - Annual cycle in LH and testosterone release in response to GnRH challenge in male
      woodchucks (Marmota monax).
AB  - Testosterone and LH concentrations were determined in serum samples obtained
      before and 15 min after injections of GnRH (1 microgram kg-1) administered at 4-7
      week intervals over 20 months to groups of male woodchucks (n = 6-7) born and
      maintained in Northern Hemisphere (boreal) versus Southern Hemisphere (austral)
      simulated natural photoperiods, beginning at 18-24 months of age. Nadir and peak
      unstimulated testosterone (0.1 +/- 0.01 and 7.0 +/- 0.1 ng ml-1, respectively)
      and LH (0.8 +/- 0.2 and 8.1 +/- 1.1 ng ml-1, respectively) concentrations did not
      differ in boreal versus austral males. In the five boreal and five austral males
      that were confirmed to be photoentrained, basal (pre-GnRH) concentrations of LH
      and testosterone were lowest in summer, increased simultaneously in late autumn
      or early winter, and declined in the spring. GnRH stimulated some LH release
      throughout the year except for a 1-4 month period in the summer. The initial
      annual increase in the LH response to GnRH occurred in early autumn, and in 17 of
      20 cycles it occurred 1-2 months before the initial increase in basal LH was
      detected. In the three free-running males not entrained to the photoperiod, the
      endocrine patterns were similar but were advanced by several months. The results
      demonstrate that in woodchucks there is a late autumn increase in LH secretion
      associated with the onset of testicular recrudescence, and an early autumn
      increase in pituitary response to GnRH before a detectable increase in serum
      testosterone.

PMID- 10070361
TI  - Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the
      white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus
      ater, with observations on intermediate filament proteins in the decidua and
      intraplacental trophoblast.
AB  - Histological and immunocytochemical studies of gravid reproductive tracts
      obtained from the white-winged vampire bat (Diaemus youngi) and the black mastiff
      bat (Molossus ater) have established that both species develop unusually invasive
      trophoblast. This is released by the developing discoidal haemochorial placenta,
      expresses both cytokeratins and vimentin, and invades the myometrium and adjacent
      tissues (including the ovaries) via interstitial migration within the walls of
      maternal blood vessels. Hence, this trophoblast is noteworthy for the extent to
      which it undergoes an epithelial-mesenchymal transformation. In Molossus, it
      originates from the cytotrophoblastic shell running along the base of the
      placenta, is mononuclear, and preferentially invades maternal arterial vessels
      serving the discoidal placenta. This trophoblast may have a role in dilatation of
      these vessels when the discoidal placenta becomes functional. In Diaemus, the
      highly invasive trophoblast appears to originate instead from a layer of
      syncytiotrophoblast on the periphery of the placenta is multinucleated, and
      vigorously invades both arterial and venous vessels. During late pregnancy, it
      becomes extensively branched and sends attenuated processes around many of the
      myometrial smooth muscle fibres. In view of its distribution, this trophoblast
      could have important influences upon myometrial contractility and the function of
      blood vessels serving the gravid tract. Other aspects of intermediate filament
      expression in the uteri and placentae of these bats are also noteworthy. Many of
      the decidual giant cells in Molossus co-express cytokeratins and vimentin, while
      the syncytiotrophoblast lining the placental labyrinth in Diaemus late in
      pregnancy expresses little cytokeratin.

PMID- 10070362
TI  - Trophectoderm differentiation in the bovine embryo: characterization of a
      polarized epithelium.
AB  - Blastocytst formation is dependent on the differentiation of a transporting
      epithelium, the trophectoderm, which is coordinated by the embryonic expression
      and cell adhesive properties of E-cadherin. The trophectoderm shares
      differentiative characteristics with all epithelial tissues, including E-cadherin
      mediated cell adhesion, tight junction formation, and polarized distribution of
      intramembrane proteins, including the Na-K ATPase. The present study was
      conducted to characterize the mRNA expression and distribution of polypeptides
      encoding E-cadherin, beta-catenin, and the tight junction associated protein,
      zonula occludens protein 1, in pre-attachment bovine embryos, in vitro.
      Immunocytochemistry and gene specific reverse transcription--polymerase chain
      reaction methods were used. Transcripts for E-cadherin and beta-catenin were
      detected in embryos of all stages throughout pre-attachment development.
      Immunocytochemistry revealed E-cadherin and beta-catenin polypeptides evenly
      distributed around the cell margins of one-cell zygotes and cleavage stage
      embryos. In the morula, detection of these proteins diminished in the free apical
      surface of outer blastomeres. E-cadherin and beta-catenin became restricted to
      the basolateral membranes of trophectoderm cells of the blastocyst, while
      maintaining apolar distributions in the inner cell mass. Zonula occludens protein
      1 immunoreactivity was undetectable until the morula stage and first appeared as
      punctate points between the outer cells. In the blastocyst, zonula occludens
      protein 1 was localized as a continuous ring at the apical points of
      trophectoderm cell contact and was undetectable in the inner cell mass. These
      results illustrate that the gene products encoding E-cadherin, beta-catenin and
      zonula occludens protein 1 are expressed and maintain cellular distribution
      patterns consistent with their predicted roles in mediating trophectoderm
      differentiation in in vitro produced bovine embryos.

PMID- 10070363
TI  - Protective effect of vitamin E on ischaemia-reperfusion injury in ovarian grafts.
AB  - Ovarian cortical tissue cryopreservation with subsequent autografting is a
      potential strategy for the preservation of fertility in patients undergoing
      systemic chemotherapy and pelvic radiotherapy. Non-vascular implants are first
      subjected to a period of ischaemia before revascularization and are, therefore,
      vulnerable to ischaemia-reperfusion injury from reactive oxygen species.
      Ischaemia-reperfusion injury was investigated during the first week after surgery
      in murine ovarian grafts and human ovarian xenografts in mice with severe
      combined immune deficiency (SCID) by measuring total lipid peroxides and
      malondialdehyde concentrations with a colorometric assay. The effects of
      administering an antioxidant, vitamin E, on these concentrations were also
      tested. Products of lipid peroxidation were higher in non-supplemented murine
      autografts compared with control ovaries (P < 0.05), and were significantly
      reduced on day 3 by vitamin E administration (P < 0.05). Similarly, in human
      xenografts, there was a significant reduction in lipid peroxidation with vitamin
      E administration. These results correspond to a significantly greater total
      follicle survival in the murine grafts of the supplemented group (45 versus 72%;
      P < 0.05). They suggest that antioxidant treatment improves the survival of
      follicles in ovarian grafts by reducing ischaemia-reperfusion injury.

PMID- 10070364
TI  - Matrilysin activity in the rat uterus during the oestrous cycle and implantation.
AB  - The objective of this study was to follow changes in the activity of the small
      matrix metalloproteinase matrilysin (MMP-7) in the rat uterus during the oestrous
      cycle and embryo implantation. Matrilysin was extracted from rat uteri, partially
      purified and separated into active and latent forms. The two forms of the enzyme
      were quantified at all stages of the oestrous cycle and after oestradiol and
      progesterone treatment. The activity was also measured during the first 7 days of
      pregnancy. Both latent and active forms of MMP-7 reached a peak during the pro
      oestrous stage of the cycle; the concentrations were three times higher than at
      dioestrus and metoestrus. In rats treated with 0.1 mg oestradiol at metoestrus,
      both latent and active forms of the enzyme increased by more than two-fold after
      24 h. In rats treated at pro-oestrus with 0.4 mg progesterone, there was a 70%
      increase in latent MMP-7, but no change in the active form. The highest
      concentrations of MMP-7 were observed on the first day of pregnancy. Between days
      3 and 7 of pregnancy, the concentrations were relatively constant and comparable
      to the low concentrations at dioestrus. Enzyme activities were not different at
      implantation sites compared with remote sites.

PMID- 10070365
TI  - Heat shock protein expression in umbilical artery smooth muscle.
AB  - Postpartum vasospasm in the umbilical arteries may be due to impaired
      vasorelaxation secondary to alterations in the expression of heat shock proteins.
      The contractile responses of pre- and full-term bovine umbilical artery smooth
      muscles were determined in a muscle bath. Heat shock protein expression was
      determined in bovine and human arterial tissues using western blotting with
      specific antisera. Full-term bovine and human umbilical artery smooth muscle was
      refractory to relaxation induced by the nitric oxide donor, sodium nitroprusside.
      This impaired vasorelaxation was associated with the expression of the inducible
      form of the heat shock protein, HSP70i, and increases in the expression of the
      small heat shock protein, HSP27. Small heat shock proteins have been implicated
      in modulating contraction and relaxation responses in vascular smooth muscles.
      Thus, alterations in heat shock protein expression may play a role in umbilical
      artery vasospasm.

PMID- 10070366
TI  - Regulated expression of cadherin-11 in human extravillous cytotrophoblasts
      undergoing aggregation and fusion in response to transforming growth factor beta
      1.
AB  - Transforming growth factor beta 1 is believed to be a key regulator of
      extravillous cytotrophoblast invasion during the first trimester of pregnancy. In
      addition, this growth factor has been shown to regulate cellular differentiation
      and fusion in cultured extravillous cytotrophoblasts. To date, the cellular
      mechanisms by which transforming growth factor beta 1 promotes these
      developmental processes remain poorly understood. Recent studies indicate that
      the expression of the novel cadherin subtype, known as cadherin-11, is associated
      with the terminal differentiation and fusion of villous cytotrophoblasts isolated
      from the human term placenta and human myoblasts in vitro. In this study,
      cadherin-11 mRNA and protein expression were examined in primary cultures of
      human extravillous cytotrophoblasts cultured in the presence of increasing
      concentrations of transforming growth factor beta 1 using northern and western
      blot analysis, respectively. Transforming growth factor beta 1 was shown to
      increase cadherin-11 mRNA and protein expression in these cultured extravillous
      cytotrophoblasts in a dose-dependent manner. Cadherin-11 was further localized to
      the large cellular aggregates and multinucleated cells that formed in response to
      increasing concentrations of transforming growth factor beta 1 using
      immunocytochemistry. Collectively, these observations suggest that the
      morphogenetic effects of transforming growth factor beta 1 on cultured
      extravillous cytotrophoblasts are mediated, at least in part, by an increase in
      cadherin-11 expression. This study not only adds to the understanding of the
      cellular mechanisms by which transforming growth factor beta 1 promotes
      trophoblast differentiation and fusion but provides useful insight into the cell
      biology of the cadherins.

PMID- 10070367
TI  - 'Changing minds': banishing the stigma of mental illness.

PMID- 10070368
TI  - Interactive television and the NHS: too much television could be bad for your
      health.

PMID- 10070369
TI  - The discovery and early use of cortisone.

PMID- 10070370
TI  - Management and outcome of patients undergoing surgery after acute upper
      gastrointestinal haemorrhage. Steering Group for the National Audit of Acute
      Upper Gastrointestinal Haemorrhage.
AB  - Most patients with acute upper gastrointestinal haemorrhage are managed
      conservatively or with endoscopic intervention but some ultimately require
      surgery to arrest the haemorrhage. We have conducted a population-based
      multicentre prospective observational study of management and outcomes. This
      paper concerns the subgroup of 307 patients who had an operation because of
      continued or recurrent haemorrhage or high risk of further bleeding. The
      principal diagnostic group was those with peptic ulcer. Of 2071 patients with
      peptic ulcer presenting with acute haemorrhage, 251 (12%) had an operative
      intervention with a mortality of 24%. In the non-operative group mortality was
      10%. The operative intervention rate increased with risk score, ranging from 0%
      in the lowest risk categories to 38% in the highest. Much of the discrepancy
      between operative and non-operative mortality was explainable by case mix;
      however, for high-risk cases mortality was significantly higher in the operated
      group. In 78% of patients who underwent an operation for bleeding peptic ulcer
      there had been no previous attempt at endoscopic haemostasis. For patients
      admitted to surgical units, the operative intervention rate was about four times
      higher than for those admitted under medical teams. In patients with acute upper
      gastrointestinal haemorrhage operative intervention is infrequent and largely
      confined to the highest-risk patients. The continuing high mortality in
      surgically treated patients is therefore to be expected. The reasons for the low
      use of endoscopic treatment before surgery are not revealed by this study, but
      wider use of such treatments might further reduce the operative intervention
      rate. Physicians and surgeons have not yet reached consensus on who needs surgery
      and when.

PMID- 10070371
TI  - The one-stop dyspepsia clinic--an alternative to open-access endoscopy for
      patients with dyspepsia.
AB  - The most sensitive investigative tool for the upper gastrointestinal tract is
      endoscopy, and many gastroenterologists offer an open-access endoscopy service to
      general practitioners. However, for patients with dyspepsia, endoscopy is not
      always the most appropriate initial investigation, and the one-stop dyspepsia
      clinic allows for different approaches. We have audited, over one year, the
      management and outcomes of patients attending a one-stop dyspepsia clinic. All
      patients seen in the clinic were included, and for those not endoscoped the notes
      were reviewed one year after the end of the study to check for reattendances and
      diagnoses originally missed. Patients' and general practitioners' views of the
      service were assessed by questionnaire. 485 patients were seen, of whom 301 (62%)
      were endoscoped at first attendance. In 66 patients (14%), endoscopy was deemed
      inappropriate and only one of these returned subsequently for endoscopy. 118
      patients (24%) were symptom-free when seen in the clinic and were asked to
      telephone for an appointment if and when symptoms recurred; half of these
      returned and were endoscoped. Oesophagitis and duodenal ulcer were significantly
      more common in this 'telephone endoscopy' group than in those endoscoped straight
      from the clinic. Overall, 25% of patients referred were not endoscoped. Important
      additional diagnoses were made from the clinic consultation. General
      practitioners and patients valued the system, in particular the telephone
      endoscopy service. 84% of general practitioners said they would prefer the one
      stop dyspepsia clinic to open-access endoscopy.

PMID- 10070372
TI  - Consent obtained by the junior house officer--is it informed?
AB  - Of 30 junior house officers questioned, 21 had obtained patients' consent for
      colonoscopy. Of these 21, about one-third did not routinely discuss with patients
      the risks of perforation and haemorrhage. Ideally, consent should be obtained by
      a person capable of performing the procedure. If it is to be obtained by junior
      house officers, they need to know exactly what must be disclosed about each
      procedure. This could easily be done as part of the induction package.

PMID- 10070373
TI  - Traumatic stress--is prevention better than cure?

PMID- 10070374
TI  - Taeniasis and cysticercosis.

PMID- 10070375
TI  - Male menopause after unilateral inguinal herniorrhaphy.

PMID- 10070376
TI  - Child psychosis due to hypothyroidism.

PMID- 10070377
TI  - Accidental ingestion of a dental instrument.

PMID- 10070378
TI  - Basal cell carcinoma of the scalp with spinal metastasis.

PMID- 10070379
TI  - Vitreous haemorrhage in Fanconi's anaemia.

PMID- 10070380
TI  - Short gastric artery perforation after use of 'ecstasy'.

PMID- 10070381
TI  - Pulmonary embolism in Klippel-Trenaunay syndrome of the upper limb.

PMID- 10070382
TI  - Sigmoido-appendiceal fistula due to diverticulitis.

PMID- 10070383
TI  - Foreign body perforation of lymphoma.

PMID- 10070384
TI  - Weeding Mozart's medical history.

PMID- 10070385
TI  - Richard Morton's Phthisiologia.

PMID- 10070386
TI  - Triage of back pain by physiotherapists in orthopaedic clinics.

PMID- 10070387
TI  - Nerve injury from false aneurysm.

PMID- 10070388
TI  - Diagnosis of the acute red eye.

PMID- 10070389
TI  - Training of surgeons.

PMID- 10070390
TI  - Safety of herbal remedies.

PMID- 10070391
TI  - Healing research in general practice.

PMID- 10070392
TI  - Limited private practice--to be or not to be?

PMID- 10070393
TI  - Dangers of short intravenous lines and intravenous outpatient antibiotic therapy
      (OPAT)

PMID- 10070394
TI  - Pre-test counselling for HIV--short and friendly please.

PMID- 10070395
TI  - Misoprostol and Mobius syndrome.

PMID- 10070396
TI  - A rapid screening test for pleural exudates.

PMID- 10070397
TI  - Roche responds to 'new warnings on the use of isotretinoin (Roaccutane)'.

PMID- 10070398
TI  - Roaccutane--a dermatologist's perspective.

PMID- 10070399
TI  - 693 drugs in essential drugs list.

PMID- 10070400
TI  - Health and human rights into the new millennium.

PMID- 10070401
TI  - Zuma pacifies pharmaceutical manufacturers.

PMID- 10070404
TI  - The costing of HIV/AIDS--without a clue?

PMID- 10070405
TI  - Cheaper to manage HIV than to treat AIDS--the Medscheme experience.

PMID- 10070406
TI  - Saving tax on holiday and education expenses.

PMID- 10070407
TI  - Kangaroo mother care.

PMID- 10070408
TI  - A novel method for constructing an alternative spacer for patients with asthma.

PMID- 10070409
TI  - Boerhaave's syndrome--ruptured oesophagus, with mediastinal abscess.

PMID- 10070410
TI  - Hepatitis B serology.

PMID- 10070411
TI  - Chronic lymphocytic leukaemia--a personal story.

PMID- 10070412
TI  - Surgeons and trauma--the great South African love-hate phenomenon.

PMID- 10070413
TI  - Non-chemotherapy modulation of malignant lymphocytosis.

PMID- 10070414
TI  - Risk factors for meningococcal disease in Cape Town.
AB  - OBJECTIVE: To determine the risk factors associated with meningococcal disease
      among children living in Cape Town. DESIGN: A case-control study was conducted
      from October 1993 to January 1995. SETTING: The study population consisted of all
      children under the age of 14 years who were resident in the Cape Town
      metropolitan region. Cases and controls were selected from Red Cross War Memorial
      Children's Hospital. RESULTS: A total of 70 cases and 210 controls were
      interviewed. Significant risk factors for meningococcal disease included being
      breast-fed for less than 3 months (adjusted odds ratio (OR) 2.4); overcrowding
      (adjusted OR 2.3); and age less than 4 years (adjusted OR 2.3). Exposure to two
      or more household members who smoked was also a risk factor, but only in the
      presence of a recent upper respiratory tract infection (adjusted OR 5.0).
      CONCLUSION: This is the first case-control study in South Africa examining risk
      factors for meningococcal disease. It provides further evidence for reduction of
      smoking, reduction of overcrowding and promotion of breast-feeding as important
      public health measures.

PMID- 10070415
TI  - Laboratory surveillance of Shigella dysenteriae type 1 in KwaZulu-Natal.
AB  - OBJECTIVE: To collect data on the antimicrobial susceptibility of Shigella
      dysenteriae type 1 in KwaZulu-Natal, including the testing of newer therapeutic
      agents, and to evaluate the ability of laboratories to participate in a
      provincial surveillance programme. DESIGN: Prospective descriptive study.
      SETTING: Hospital laboratories in KwaZulu-Natal, including peripheral
      laboratories and the medical microbiology laboratory of the University of Natal.
      MAIN OUTCOME MEASURES: Antimicrobial susceptibility pattern of surveillance
      strains and evaluation of the ability of provincial laboratories to isolate
      Shigella. RESULTS: All 354 strains tested were resistant to ampicillin,
      chloramphenicol and tetracycline. Co-trimoxazole resistance was found in 92.2% of
      strains, and 0.8% of strains were resistant to nalidixic acid. All strains were
      susceptible to ceftriaxone, ciprofloxacin, ofloxacin, pivmecillinam,
      azithromycin, loracarbef and fosfomycin. Of the 29 laboratories surveyed, 18
      (62.1%) were able to isolate and identify S. dysenteriae correctly, and 9 (32%)
      were able to serotype it further to S. dysenteriae type 1. Twenty-seven (93.1%)
      had appropriate culture media and 26 (89.7%) had antisera for Shigella
      identification. CONCLUSIONS: There is little variation among strains of S.
      dysenteriae type 1 in KwaZulu-Natal with regard to their antimicrobial
      susceptibility pattern. Nalidixic acid should remain the antimicrobial of choice
      for treatment of dysentery in our region as resistance to it is low. The majority
      of KwaZulu-Natal laboratories have the expertise and equipment to perform the
      isolation and identification of Shigella species.

PMID- 10070416
TI  - Stroke in rural South Africa--contributing to the little known about a big
      problem.
AB  - OBJECTIVES: To describe the extent of mortality from cerebrovascular accident
      (CVA) in a rural South African population. DESIGN: Annual demographic and health
      surveillance with verbal autopsy of all deaths, 1992-1995. OUTCOME MEASURES:
      Stroke mortality rate by age and sex. RESULTS: Stroke mortality increased with
      age and is higher in men than women over age 35. Proportionate mortality ratio
      from CVA: 10.3% of deaths in the 35-64-year age group. CONCLUSION:
      Cerebrovascular disease is an important cause of death in South Africa's rural
      north-east. Community-based research is needed to inform policy and practice.

PMID- 10070417
TI  - A pathology-based cancer registry for black South African children and
      adolescents--12-year data analysis.

PMID- 10070418
TI  - Psychologists' right to prescribe--should prescribing privileges be granted to
      South African psychologists?
AB  - Current changes in legislation regarding prescription rights increase the
      possibility of non-medical practitioners being authorized to prescribe
      medication. There has been ongoing debate about granting psychologists in South
      Africa a limited right to prescribe (RTP) psychotropic medication. The main
      reasons advanced for granting psychologists RTP include the advantage of
      delivering integrated treatments, with psychologists well placed to offer such
      treatment, and the shortage of mental health practitioners in South Africa. If
      psychologists were granted the RTP they would have to undergo extensive training
      in psychopharmacology. Curricula for such training are currently being prepared
      with the help of the American Psychological Association. But there is also
      considerable opposition to psychologists being granted the RTP, both from within
      psychology and from other quarters. Opposition from outside psychology is based
      largely on safety considerations relating to lack of relevant training among
      psychologists. Opposition from within psychology is based on a concern about the
      loss of the distinctive contribution of psychology to mental health care in South
      Africa. Various aspects of this debate are examined in this paper.

PMID- 10070419
TI  - Hospitals in Cape Town during the Anglo-Boer War.
AB  - The choice of Cape Town as the site for the base hospitals during the Anglo-Boer
      War was for many reasons a logical one. The hospitals that existed in the city at
      the time were inadequate in size and lacked the required facilities. The
      unexpectedly large number of wounded and the epidemics of typhoid and plague
      demanded an ever-increasing number of hospital beds. These demands were met by
      expanding existing hospitals making use of temporary hospitals and converting
      other buildings into hospitals. Eventually more than 3,000 beds were made
      available by the 10 hospitals in Cape Town and the system, despite continuing
      problems, provided a reasonable service under difficult circumstances.

PMID- 10070420
TI  - Brain biopsy in AIDS patients: what are the indications?

PMID- 10070421
TI  - Primary transsphenoidal microsurgery in the treatment of craniopharyngiomas.
AB  - Thirty craniopharyngiomas were operated on between 1983 and 1993. Eight patients
      underwent surgery solely via the transsphenoidal route. None of these had
      undergone surgery previously. The eight patients were followed up for a period of
      120 months (mean 87.5 months). The tumour was removed totally in five and
      subtotally in three patients. All eight patients had one or more endocrine
      abnormalities prior to surgery. Five patients presented with visual field defects
      or decreased visual acuity, which improved postoperatively in all cases. Seven
      received radiotherapy, with one declining this treatment. No recurrences have
      occurred during follow-up in any of the group. Primary transsphenoidal surgery is
      a both safe and effective treatment for those craniopharyngiomas that are located
      within an enlarged sella, have no calcification and are not adherent to
      parasellar structures.

PMID- 10070422
TI  - The neuronal cytoskeleton in acute brain injury.
AB  - The microtubules, neurofilaments and microfilaments of the neuronal cytoskeleton
      are essential for the normal functioning of the neurone. Recent studies have
      shown that disruption of the cytoskeleton may represent a final pathway in many
      types of neuronal cell injury with both the somato-dendritic and axonal
      cytoskeleton being affected. This review discusses the current evidence on the
      role of the neuronal cytoskeleton in the pathogenesis of traumatic brain damage.

PMID- 10070423
TI  - Prognostic factors in supratentorial WHO grade II astrocytoma in adults.
AB  - The records of 33 adult patients with supratentorial World Health Organization
      grade II astrocytoma (A-II) treated between January 1980 and April 1997 at our
      hospitals were retrospectively reviewed. All tumours were surgically resected or
      biopsied and their MIB-1 labelling indices (LIs) were less than 1.5%. The median
      time to tumour progression after the initial surgery was 60 months, and the 5-
      and 10-year tumour progression-free rates were 53 and 39%, respectively. The
      median survival time was 107 months, and the 5- and 10-year survival rates were
      66 and 43%, respectively. The major cause of death was tumour recurrence with
      malignant transformation, comprising 93% of all deaths due to unrestrained tumour
      growth. In a univariate analysis for survival rate by log-rank test, age (< 60
      years), Karnofsky Performance Scale score (90-100%), tumour location (except for
      the basal ganglia), and extent of surgery (more than biopsy) were revealed to be
      significant positive prognostic factors. A Cox proportional hazard multivariate
      regression analysis confirmed that the age was the only independent, significant
      positive prognostic factor in this series. The survival time after the initial
      surgery in patients without radiotherapy tended to be prolonged compared with
      those of the patients with radiotherapy. Of the 26 patients who received
      radiotherapy, however, the survival time after the initial surgery in the nine
      patients with intraoperative radiotherapy was significantly prolonged compared
      with the 17 patients who received sole external beam radiotherapy. Gender,
      symptoms, histology, p53 LI, enhancement on CT/MRI, cyst, calcification and
      chemotherapy were not shown to be significant prognostic factors. The optimal
      management strategy for A-II is expected to be established by clarification of
      the natural history with cytological and molecular biological analyses of the
      biological features of this disease.

PMID- 10070424
TI  - The management of brain abscess in a developing country: are the results any
      different?
AB  - A retrospective study of 57 surgically-managed brain abscesses at the
      Neurosurgical Unit, Bir Hospital during a 6-year period from October 1990 is
      presented. Detailed hospital case notes could be traced in only 37 cases,
      consisting of 25 males and 12 females with age range from 5 months to 60 years.
      Cryptogenic abscess was the commonest category followed by abscess caused by
      chronic ear infection. The diagnosis was made with enhanced computed tomography
      (CT) in all the cases. Positive bacteriology was found in only nine cases. The
      treatment consisted of 6 weeks of intensive intravenous antibiotics and emergency
      surgical drainage of the abscess. Five out of the total cases died (13.5%). These
      patients were all in an extremely poor condition at the time of presentation. All
      the survivors made a good recovery. With timely CT diagnosis, surgical drainage
      and antibiotics, good results can be achieved even in a developing country.

PMID- 10070425
TI  - 'Safe neurosurgery'. How are we doing three years on?
AB  - 'Safe Neurosurgery' a document setting out standards of practice in British
      neurosurgery was published in 1993. Three years later we have looked at how much
      of an impact this extremely important document has made. We have been
      disappointed to discover that overall there has been little change for the
      better. The paper illustrates the changes seen over the 3 years.

PMID- 10070426
TI  - A new lesion for the psychosurgical operation of stereotactic subcaudate
      tractotomy (SST)
AB  - The psychosurgical treatment of psychiatric illnesses, using stereotactic
      subcaudate tractotomy (SST), has been carried out at the Geoffrey Knight Unit
      since 1961. Recently, the procedure has had to be modified. This paper describes
      the manner in which this has been achieved and the clinical implications of this
      change.

PMID- 10070427
TI  - Penetrating craniocerebral injuries: an escalating problem in Pakistan.
AB  - We carried out a prospective study on patients admitted to busy neurosurgical
      units in Karachi and Quetta with penetrating craniocerebral injuries. Of the 100
      patients, 52 died and 48 survived in spite of aggressive surgical management.
      Maximum mortality was in patients with Glasgow Coma Score (GCS) below 5. A delay
      of 6 h, delay in interhospital transfers, and limited post operative aggressive
      management led to further secondary insults to the brain contributing to a poorer
      outcome. A review of current literature on pathophysiology and management is
      included and the importance of prehospital optimum care, and early transfer to
      the neurosurgical centre are emphasized. Since only two of the 35 patients with a
      GCS of less than five survived, with severe disabilities, utilizing resources in
      third world countries on the management of craniocerebral penetrating injuries in
      patients with a GCS less than 5 is questioned especially when organ donation is
      not possible.

PMID- 10070428
TI  - Atypical response to chemotherapy in neurotuberculosis.
AB  - Five cases of intracranial tuberculosis with atypical response to antitubercular
      chemotherapy are reported. In these cases tuberculomas either increased in sizes
      or first developed during course of adequate chemotherapy for tubercular
      meningitis or postmeningitic hydrocephalus. In two of these cases granulomas were
      located deeply in the parenchyma; however, these were on the surface in the other
      three. Atypical response to antitubercular treatment was observed at 5 weeks, 8
      weeks, 2 months (in two cases) and 6 months. Glucocorticoid therapy was
      instituted in two cases and surgical excision of tuberculomas performed in the
      others. Recovery was good in all the five cases excluding visual loss, which
      remained unchanged in two cases because of prexisting secondary optic atrophy.

PMID- 10070429
TI  - Recommendations from the Society of British Neurological Surgeons.

PMID- 10070430
TI  - Simple delineation of misery perfusion areas by superimposition of PET on PET
      images.
AB  - Oxygen extraction fraction images were superimposed on cerebral blood flow images
      of positron emission tomography (PET) to depict the so-called misery perfusion
      area in two patients with moyamoya disease. The superimposed image following
      extra-intracranial bypass surgery was obtained in one case, which convincingly
      disclosed attenuation as compared with the preoperative image. This simple PET on
      PET approach should find an application in the evaluation of misery perfusion and
      in assessing operative indications for cerebral ischaemic diseases.

PMID- 10070431
TI  - Delayed recurrence of cerebellar abscess 20 years after excision of dermoid cyst
      and sinus.
AB  - A patient is described who suffered a greatly delayed reappearance of a
      cerebellar abscess, 20 years after excision, in childhood, of a midline dermoid
      cyst with associated abscess formation. A similar organism was cultured on both
      occasions.

PMID- 10070432
TI  - Craniopharyngioma invading the nasal and paranasal spaces, and presenting as
      nasal obstruction.
AB  - A case of craniopharyngioma invading the nasal and paranasal sinuses and
      presenting as nasal obstruction is reported. Imaging showed a destructive mass of
      the skull base with involvement of the nose and paranasal sinuses. In the excised
      mass mitoses were frequent and the proliferation index was high. Invasion of the
      nasopharynx and presentation as a nasopharyngeal mass is uncommon for a
      craniopharyngioma.

PMID- 10070433
TI  - Multiple postoperative intracerebral haematomas remote from the site of
      craniotomy.
AB  - A postoperative haemorrhage is a common and serious complication of a
      neurosurgical procedure. It usually occurs at the site of the surgery, but on
      occasion a postoperative haematoma is found at a distance from the previous
      craniotomy. Multiple postoperative haemorrhages are extremely rare. We report the
      case of a 63-year-old woman, operated on for the removal of a supratentorial
      astrocytoma, who developed in the early post-operative period multiple bilateral
      intracerebral haematomas without involvement of the surgical bed.

PMID- 10070434
TI  - Non-surgical treatment of meningioma: a case report and review.
AB  - A woman initially presented with a right hemiparesis and subsequently underwent
      subtotal resection of a left parietal meningioma arising from the lateral wall of
      the sagittal sinus. She again presented 18 months after surgery with a
      hemiparesis and repeat MRI showed tumour spreading into the sagittal and the
      transverse sinuses. She had a therapeutic abortion at 8 weeks gestation 3 weeks
      prior to her representation. Gestrinone, a synthetic steroid and an
      antiprogesterone was commenced. Two months later she stopped her medication and
      is asymptomatic at 16 months. A follow-up MRI revealed that the tumour had shrunk
      dramatically. This case is the first of its kind with tumour size reduction to
      less than 20%. We feel that the future of meningioma treatment will be multi
      disciplinary and non-surgical options should be considered.

PMID- 10070435
TI  - Recurrent subdural haematoma as the primary and sole manifestation of chronic
      lymphocytic leukaemia.
AB  - An 81-year-old man with a recurrent subdural haematoma as the first and only
      manifestation of chronic lymphocytic leukaemia (CLL) is described. Microscopic
      examination of the encapsulated haematoma showed leukaemic infiltration and the
      diagnosis was confirmed by bone marrow aspiration and by pathological examination
      of the brain at autopsy.

PMID- 10070436
TI  - Internuclear ophthalmoplegia following minor head injury: a case report.
AB  - Internuclear ophthalmoplegia (INO) is a common sign of multiple sclerosis in
      young patients and of vascular diseases in older people. Traumatic bilateral
      internuclear ophthalmoplegia following severe head injuries may occur. We present
      the unusual case of a young patient suffered from bilateral INO as an isolated
      finding after a minor head injury, without other signs of brain stem or cortical
      injury. The ophthalmoplegia has persisted for 22 months.

PMID- 10070437
TI  - Dural osteochondroma: case report, review of the literature and proposal of a new
      classification.
AB  - Complete excision of a dural osteochondroma is presented. Upon reviewing the
      literature we noted that basal and convexity osteochondromas, although considered
      as a single pathological entity, differ in epidemiology, pathogenesis, management
      and natural history. A new classification is proposed.

PMID- 10070438
TI  - Microsurgical approaches to orbital lymphoma.

PMID- 10070439
TI  - Britain in Europe: training the neurosurgeons of the future.

PMID- 10070440
TI  - Failure to follow patients with hydrocephalus shunts can lead to death.
AB  - Failure to follow patients with hydrocephalus can expose them to potentially
      fatal consequences. Two cases are used to illustrate this and the merits of
      follow-up of these patients are discussed.

PMID- 10070441
TI  - The differential effect of the level of spinal cord stimulation on patients with
      advanced peripheral vascular disease in the lower limbs.
AB  - Percutaneous spinal cord stimulation (SCS) (Medtronic model 3487A PISCES-Quad
      lead) was carried out in 10 patients with rest pain from advanced peripheral
      vascular disease of the lower limb, who were unsuitable for conventional
      treatment. Trial stimulation ranged from 1-20 weeks and was associated with pain
      relief in nine of the patients. Claudication distance was improved in six
      patients. Trophic lesions improved in one patient with small artery disease.
      Spinal cord stimulation did not reverse the course of acute gangrenous lesions.
      The distal arterial pressure measured by Doppler Ankle/Brachial Pressure Index,
      (ABPI), showed no change. The capillary blood flow and skin temperature of both
      feet, measured, respectively, by Laser Doppler flowmetry and skin thermistor,
      showed a tendency to decrease when the stimulation was at the higher level, above
      T10, compared with an increase when the stimulation was at the lower level T12.
      Transcutaneous oxygen tension monitoring of the symptomatic foot showed an
      increase in four out of five patients. Pain relief was not dependent on
      circulatory changes, but it was more significant when the circulatory changes
      showed an impressive increase in the blood flow. The mechanism of these
      circulatory changes is probably by modulation of the sympathetic nervous system.
      Recognition of the optimal sitting of SCS may be critical in the clinical use of
      this technique, which seems to be a valuable option in the treatment of patients
      with advanced peripheral vascular disease (PVD).

PMID- 10070442
TI  - Pressor and depressor responses in thermocoagulation of the trigeminal ganglion.
AB  - We have undertaken a retrospective analysis in 126 patients with trigeminal
      neuralgia on which a free-hand percutaneous thermocoagulation of the Gasserian
      ganglion was performed in our department. We focused on the occurrence of
      intraoperative vagal reactions, i.e. significant bradycardia and changes in blood
      pressure during the course of the procedure. Operative and anaesthetic records of
      patients who underwent the procedure were evaluated and correlated with clinical
      data from the patient's history. We observed the occurrence of vagal reactions
      i.e. significant bradycardia (< 50/min) or syncope in 20% of patients (p <
      0.0002) during or immediately after penetration of the foramen ovale. No
      correlation between the operated side and the occurrence of vagal reactions was
      found. A significant rise in blood pressure levels (about 180 mmHg systolic) was
      observed in 36% of patients during thermocoagulation. We concluded that painful
      stimuli arising from lesioning in the course of the trigeminal nerve reach the
      mid-brain and may irritate the dorsal nucleus of the vagus nerve resulting in
      significant bradycardia or cardiac synode. To prevent haemodynamic deterioration
      i.v. atropine (0.5-2 mg) should be available when advancing the needle, while
      anti-hypertensive medication (Esmolol) may be needed during coagulation.

PMID- 10070443
TI  - Role of ischaemia in the genesis of oedema surrounding meningiomas assessed using
      magnetic resonance imaging and spectroscopy.
AB  - Oedema surrounding meningiomas is well known, but its pathogenesis remains
      obscure. Perfusion and metabolism in this peritumoural parenchyma were studied
      preoperatively in eight patients using magnetic resonance imaging, dynamic
      perfusion scanning and proton spectroscopy. Relative cerebral blood volumes (CBV)
      and metabolite ratios were calculated for the tumour and peritumoural brain. All
      meningiomas showed gadolinium enhancement, high choline (Ch), low creatine (Cr)
      and low N-acetyl aspartate (NAA) [Ch: (Ch + Cr) 0.67, SD 0.13, NAA: (Ch + Cr)
      0.18, SD 0.15]. Lactate was present in four tumours [lactate: (Ch + Cr) 0.32, SD
      0.27]. Extremely low gadolinium passage and low CBV were seen in the 2 cm
      peritumoural region, with elevated lactate [lactate: (Ch + Cr) 0.26, SD 0.18].
      Four centimetres from tumour margin the CBV was still reduced (65, SD 20% with
      less lactate [lactate: (Ch + Cr) 0.12, SD 0.01]. Relative CBV is reduced around
      meningiomas and is associated with lactate, suggesting that oligaemia and altered
      metabolism may be part of the pathology in peritumoural oedema. Such changes may
      be important in determining functional recovery after surgery.

PMID- 10070444
TI  - Regrowth of the residual tumour after acoustic neurinoma surgery.
AB  - Ideally, acoustic neurinomas should be completely removed without neurological
      deficit. In some cases, however, removal is subtotal in order to preserve
      anatomical continuity of the facial nerve. In this report we discuss the regrowth
      of residual tumour in these patients and the difference between regrowing and
      dormant tumours. Eight of 81 patients with acoustic neurinomas where the facial
      nerve was anatomically preserved leaving tumour overlying it were investigated
      and followed-up. Only one case with residual tumour along the 7th nerve from the
      intrameatal portion to its entry to the brainstem showed regrowth 3.5 years after
      the operation. In the other seven cases with residual tumour along the nerve from
      the porus to the brainstem, the tumour remained dormant during a follow-up period
      of 4.5-8.5 years. Removal of tumour in the internal auditory meatus may make
      regrowth unlikely.

PMID- 10070445
TI  - Assessment of communication impairment and the effects of resective surgery in
      solitary, right-sided supratentorial intracranial tumours: a prospective study.
AB  - To assess the effects of solitary, right-sided supratentorial intracranial
      tumours on language and communication function patients were assessed
      preoperatively using the Western Aphasia Battery (WAB) and Boston Naming Test
      (BNT). The impact of resective tumour surgery was evaluated prospectively by a
      comparison of test scores obtained at pre- and postoperative assessments. The WAB
      scores in 33 patients revealed that 21% were by definition dysphasic (i.e.
      Aphasia Quotient < 93.8) and 35% obtained an abnormal Language Quotient.
      Performance was particularly variable on the written picture description and word
      fluency WAB subtests. Using the BNT 21% of 47 patients were anomic. The tumours
      were evenly distributed throughout the frontal, temporal and parietal lobes, but
      none were in the occipital lobe. Reassessment approximately 6 days after
      excisional tumour surgery showed that mean scores for the BNT, Aphasia Quotient,
      and the WAB spontaneous speech and comprehension subtests had improved
      significantly despite a significant reduction in dexamethasone therapy. This
      study has demonstrated that right-sided intracranial tumours produce subtle, but
      specific language deficits of a type more usually associated with left-sided
      brain dysfunction. The pathophysiological basis of these deficits is unclear, but
      they are not attributable to either limited education or pre-existing dyslexia.
      Further studies using a discriminating and comprehensive assessment of language
      in the right hemisphere are required.

PMID- 10070446
TI  - Limited unilateral approach for extramedullary spinal tumours.
AB  - Traditionally, spinal extramedullary tumours are approached by a wide multilevel
      laminectomy and a midline dural incision. This exposure may result in immediate
      or delayed instability of the spine, and exposes the spinal cord to the
      possibility of inadvertent injury during surgery. To avoid these complications
      the authors have, in 27 patients, used a limited unilateral approach to remove
      extramedullary tumours. The approach entails bone removal which is limited to the
      lateral half of the lamina on the side of the tumour and may or may not include
      the medial part of the facet joint. A lateral dural flap exposes the tumour
      without exposing the cord. Extraspinal extensions of the lesion may be approached
      by extending the laminectomy further laterally to the facet joint. This technique
      has been used in the cervical, thoracic and the lumbar spine to radically remove
      the lesion in all cases. There were no complications. The authors conclude that
      extramedullary lesions of the spine can be removed radically by this approach
      which allows direct access without cord or root retraction, and with little
      disturbance to the normal anatomy.

PMID- 10070447
TI  - Proximal aneurysms in association with arteriovenous malformations: do they
      resolve following obliteration of the malformation with stereotactic
      radiosurgery?
AB  - One-hundred consecutive patients were identified who had arteriovenous
      malformations (AVMs) treated by stereotactic radiosurgery (STRS) which were
      totally obliterated as shown by follow-up angiography. Of these cases, seven had
      intracerebral aneurysms at initial angiography, two of which were multiple. Five
      patients had saccular aneurysms at commonly recognized sites on the circle of
      Willis or main proximal cerebral arteries, while two patients had aneurysms on
      distal AVM feeder arteries in atypical sites (one saccular, one fusiform).
      Saccular aneurysms at typical sites were found to be unchanged in size following
      AVM obliteration. The significance of this finding in the management of patients
      who present with subarachnoid haemorrhage and who have both aneurysms and AVMs is
      discussed.

PMID- 10070448
TI  - The use of spring-eye needles in neurosurgery: a survey of neurosurgical theatres
      in the United Kingdom.
AB  - Spring-eye needles were commonly used in neurosurgery as a method of closure of
      craniotomy incisions because of the perceived, but not proven, advantages of easy
      handling, fast wound closure and reduced infection rate. However, these needles
      produce more tissue trauma and are more fragile. We surveyed 33 neurosurgical
      operating theatres in the UK to find out if spring eyed needles are still in use
      and, if they are not why not. We had a 91% response. The survey involved 117
      British neurosurgeons, of whom spring-eye needles were used by 38 (13%). Both
      round body and cutting needles were used, but the cutting needles have a higher
      breakage rate. The use of 'eyed' needles is rare in other surgical specialties
      but they are still in use in neurosurgical theatres; however, their use has
      declined because of changes in surgical practice, the increased breakage rate of
      these needles, and reduction of their availability.

PMID- 10070449
TI  - Embolic bacterial aneurysm of the basilar artery: case report.
AB  - A patient with basilar artery rupture caused by a septic embolus originating from
      a mitral valve vegetation is reported. The pathogenesis, investigation and
      management of infected cerebral aneurysms are reviewed.

PMID- 10070450
TI  - Spinal cord compression from precipitation of drug solute around an epidural
      catheter.
AB  - We report a previously undescribed complication of long-term epidural catheter
      placement for the administration of analgesia in terminal malignancy. Spinal cord
      compression resulted from a drug-related precipitate forming around the epidural
      catheter tip, which was successfully treated by surgical decompression.

PMID- 10070451
TI  - Primary amyloidoma of the thoracic spine.
AB  - Focal amyloidosis (amyloidoma) involving the vertebral spine without an
      underlying systemic disorder is rare. Only six cases been reported in the
      literature so far, one involving the cervical spine, the rest occurring in the
      thoracic region. We present a patient with amyloidoma involving the thoracic
      spine and describe the magnetic resonance imaging features of this condition.

PMID- 10070452
TI  - Endoscopic removal of a third ventricular cysticercal cyst.
AB  - We report the case of a young man who presented with acute obstructive
      hydrocephalus previously treated with bilateral ventriculo-peritoneal shunts.
      Previous magnetic resonance imaging studies were consistent with aqueduct
      stenosis; no intraventricular pathology was identified. Neuroendoscopy was
      performed in order the third ventricle and perform a third ventriculostomy. This
      revealed a cysticercal lesion of the third ventricle which was removed
      endoscopically. In addition, a third ventriculostomy was performed and both shunt
      systems removed. Following a course of albendazole the patient went on to make a
      full recovery, and currently remains shunt independent.

PMID- 10070453
TI  - Massive haemorrhage into acoustic neurinoma related to rapid growth of the
      tumour.
AB  - Massive haemorrhage into a acoustic neurinoma is very rare. A large size, mixed
      Antoni type and secondary vascular changes are thought to be causative factors.
      We describe a patient with a rapidly growing acoustic neurinoma which led to a
      massive haemorrhage. Rapid growth of the tumour seems to be another risk factor
      for haemorrhage.

PMID- 10070454
TI  - Retinocephalic vascular malformation: case report.
AB  - A 12-year-old boy who presented with unilateral blindness and exophthalmos was
      found to have retinocephalic vascular malformations (Bonnet-Dechaumme-Blanc
      syndrome or Wyburn-Mason Syndrome). The ophthalmic, neurological and radiological
      findings of this rare syndrome are discussed.

PMID- 10070455
TI  - Meningeal chondrosarcomas, a review of 31 patients.
AB  - We reviewed the literature to study the clinical features, the management and the
      outcome of meningeal chondrosarcomas. We included 31 patients in this review: 22
      were mesenchymal and nine were non-mesenchymal. The mean age was 27 years and 64%
      arose from the cranial meninges. The treatment was mainly total surgical
      excision. Adjuvant therapy was given to 36% of patients. Spinal meningeal
      chondrosarcomas had a better prognosis (81% 1-year survival and 45% 3-year
      survival). There were no pathognomonic clinical or radiological features. We
      concluded that the best management of meningeal chondrosarcomas is total surgical
      excision whenever possible, followed by combined course of radiotherapy and
      chemotherapy as soon as possible.

PMID- 10070457
TI  - Use of Gigli saw.

PMID- 10070456
TI  - Synovial cysts of the lumbar spine: a review.

PMID- 10070458
TI  - Brain abscess and hereditary haemorrhagic telangiectasia.

PMID- 10070459
TI  - Cavernous malformations.

PMID- 10070460
TI  - Spinal meningiomas: a 20-year review.
AB  - The long-term outcome of 78 patients with spinal meningiomas operated on over 20
      years at a single neurosurgical unit was analysed. Age, sex and tumour location
      were similar to those reported by others. Overall, 95% of our patents were
      independently mobile postoperatively, despite 25% of the group being unable to
      walk before operation, including four paraplegic patients. Only two tumours were
      entirely extradural, and a further two were both intra- and extradural. In all
      cases, tumour exposure was by posterior laminectomy, without recourse to more
      complex approaches. Complete tumour resection was achieved in 77 (98%) of cases.
      The dural attachment was excised in 20 cases and diathermy was applied in 58.
      There was one recurrence, 14 years after the original surgery. Complex and
      technically challenging surgical approaches are unnecessary to obtain complete
      removal even for anteriorly placed tumours. Excision of the dural base would seem
      unnecessary to attain a low recurrence rate.

PMID- 10070461
TI  - Neurosurgical aspects of sphenoid sinus mucocele.
AB  - The aetiological spectrum of sphenoid sinus mucocele includes congenital anomaly,
      trauma, infection, allergy and surgery of the sphenoid sinus. Enlargement of the
      mucocele, even with a short history, can result in progressive expansion of the
      sinus and extension of the lesion into the pituitary fossa, the suprasellar
      region, nasopharynx, orbits, clivus or ethmoid air cells. It is a benign cystic
      lesion with an excellent prognosis when treated appropriately. Generally, these
      lesions are managed by an ear, nose and throat surgeon, but when there is
      extension into the sellar and parasellar (especially suprasellar) regions they
      are managed by the neurological surgeon. Sphenoid sinus mucocele should be
      considered in the differential diagnosis when there is suspicion of a cystic
      lesion in these regions. Three cases of large sphenoid sinus mucocele are
      presented, with discussion on their neurosurgical management and a review of the
      literature.

PMID- 10070462
TI  - The combined use of image-guided frameless stereotaxy and neuroendoscopy for the
      surgical management of occlusive hydrocephalus and intracranial cysts.
AB  - The objective of the study was to report the initial experiences with the
      combined use of an infrared-based frameless stereotactic navigation device and
      neuroendoscopy. Ten hydrocephalic patients underwent endoscopic third
      ventriculostomy and two patients with intracranial cysts underwent
      cystoventriculostomy. The trajectory of the rigid endoscope and target point were
      planned by frameless stereotaxy. An articulated arm served to maintain the
      predetermined trajectory during the surgery and to guide the endoscope.
      Endoscopic surgery was successfully performed in 11 of the 12 patients. In one
      patient with a small third ventricle the ventriculostomy had to be abandoned. We
      observed no surgical morbidity. In none of the cases was it necessary to correct
      the predetermined trajectory of the endoscope to reach the planned target area.
      The planning of the trajectory and the target area, as well as the maintenance of
      the trajectory during endoscopy reduce the risk of inadvertent damage to vital
      structures. The combined use of frameless stereotaxy and neuroendoscopy might
      contribute to a decrease of procedure-related morbidity.

PMID- 10070463
TI  - Apoptosis in human primary brain tumours.
AB  - Apoptosis, or programmed cell death, has been recognized for nearly three decades
      as occurring in many organs in response to different pathophysiological stimuli.
      It is now recognized as one of the fundamental cellular biological processes. In
      human glioma it was initially identified as 'shrinkage necrosis'. This review
      outlines the characteristics of apoptosis in the various types of primary human
      brain tumours. The significance of apoptosis is reviewed in relation to normal
      and tumour cell dynamics, cellular susceptibility to normal and oncogenic signals
      and to potential therapeutic advances. On a practical level, methods which are
      currently used to analyse different aspects of the apoptotic process are
      introduced. These techniques for analysing apoptosis are critically evaluated and
      compared. Current developments elucidating the diverse pathways of apoptosis
      signalling are also reviewed. The potential of pro-apoptotic therapy for the
      treatment of gliomas is discussed.

PMID- 10070464
TI  - Recurrence of vestibular (acoustic) schwannomas in surgical patients where
      preservation of facial and cochlear nerve is the priority.
AB  - The risk of tumour recurrence was measured in a series of surgically treated
      vestibular (acoustic) schwannoma patients where preservation of facial and
      cochlear nerve function was a routine objective. This report describes the
      influence of this surgical philosophy on the hazards of tumour recurrence or
      continued growth from residual tumour cells left in situ. A series of 116
      consecutive vestibular schwannoma patients underwent primary surgical resection
      in a general community hospital by a single neurosurgeon. Recurrence of a tumour
      was assessed radiologically. Eighteen patients experienced a recurrence. No
      relationship was found between recurrence and age, residual coagulated morsels of
      tumour, preoperative tumour size, or opening of the internal auditory canal. Time
      to recurrence ranged from six to one hundred and forty-eight months and all but
      two recurrent lesions were non symptomatic. Lifelong follow-up of these patients
      is therefore, suggested.

PMID- 10070465
TI  - Artifacts in magnetic resonance images following anterior cervical discectomy and
      fusion: report of two cases.
AB  - Magnetic susceptibility artifacts in two patients who underwent anterior cervical
      discectomy with fusion for cervical intervertebral disc prolapse are described.
      These artifacts located at the previously operated level suggested severe ventral
      compression of the dural tube. Computed tomography (CT) confirmed the artifactual
      nature of the MR findings and delineated the possible cause for the recurrence of
      symptoms in these patients. Elements and factors that can possibly lead to MR
      susceptibility artifacts in post operative imaging are elucidated. The danger of
      using MR imaging alone in directing the management of these patients is
      highlighted.

PMID- 10070466
TI  - Unilateral fenestration in the treatment of lumbar spinal stenosis.
AB  - The results of decompression by fenestration restricted to the clinically
      relevant level and side in 50 cases of spinal stenosis are presented. Forty-two
      patients underwent unilateral and 37 single level procedures. The mean follow-up
      time was 32 months. Patient assessment of outcome was: 32% excellent, 28% good,
      28% fair, 4% marginal and 8% poor. This is comparable to published series. Two
      patients developed contralateral leg symptoms during the study. MRI showed
      neither case to be due to progressive stenosis. It is proposed that fenestration
      type surgery restricted to the clinically relevant level and side provides
      adequate spinal decompression whilst minimizing the extent of the surgical
      intervention.

PMID- 10070467
TI  - Vim thalamotomy for the relief of the intention tremor of multiple sclerosis.
AB  - We have reviewed the outcome of patients who have undergone thalamotomy for the
      intention tremor of multiple sclerosis (MS). Twenty-four patients underwent 29
      procedures between 1988 and 1995. These patients were assessed for the degree of
      disability due to MS and for the impairment of arm function due to the tremor.
      Preoperative, postoperative and last follow-up score (mean 2.2 years) were
      determined for arm function following thalamotomy. Patient satisfaction, where
      expressed, was recorded. Twenty-three procedures (79%) resulted in immediate
      improvement in arm function. Thirteen complications were recorded. Postoperative
      fatigue was demonstrated after seven procedures. Sustained benefit was seen after
      18 procedures (62%). Out of 23 patients whose opinions are recorded four were
      enthusiastic and 10 satisfied with the outcome. We conclude that, despite severe
      disability, a majority of patients with intention tremor of MS may still benefit
      from thalamotomy and are satisfied with the results.

PMID- 10070468
TI  - Cervical foraminotomy: an effective treatment for cervical spondylotic
      radiculopathy.
AB  - Between 1983 and 1994, posterior cervical foraminotomy as described by Frykholm
      was performed on 89 patients with exclusively radicular symptoms caused by
      cervical osteophytes. The main presenting feature was arm pain. Objective
      neurological signs were present in 50% of the patients. At mean postoperative
      follow-up of 8.6 months, 95.5% of patients reported excellent or good results,
      while 4.5% were not improved. No patient was rendered worse following the
      procedure. There were no deaths and the complication rate was 2.2%. Further
      surgery for recurrent root symptoms was required by 6.7% of patients. Our
      findings are in keeping with the good results and low complication rate of this
      procedure as described in other studies. Informal inquiries suggest that this
      procedure is not widely used, at any rate in the United Kingdom, and we present
      this series in order to emphasize the efficacy and safety of this procedure.

PMID- 10070469
TI  - Technique of removal of an impacted sharp object in a penetrating head injury
      using the lever principle.
AB  - Penetrating head injuries can be difficult to manage as the extensive surgery
      which may be required can result in severe morbidity and mortality in some
      patients. A conservative surgical approach with a "pull and see" policy was
      adopted successfully in a described case. Extraction can be achieved by using the
      mechanical advantage of the lever principle. By this method while removing the
      object any movements of sharp edges which will cause secondary damage can be
      reduced to a minimum.

PMID- 10070470
TI  - Giant fusiform aneurysm of the middle cerebral artery: successful Hunterian
      ligation without distal bypass.
AB  - Giant fusiform aneurysm is a rare vascular lesion which presents difficult
      management issues. We describe one such aneurysm in a middle cerebral artery
      branch (M2) that presented with subarachnoid haemorrhage and was managed
      operatively. Clinical, radiological and pathological presentations, as well as
      the different treatment options for this type of aneurysm are discussed based on
      a literature review. A satisfactory results in an M2 giant fusiform aneurysm can
      be achieved with Hunterian ligation of the parent vessel even when a distal EC-IC
      bypass is not possible.

PMID- 10070471
TI  - Pineoblastoma presenting in familial adenomatous polyposis (FAP): random
      association, FAP variant or Turcot syndrome?
AB  - Brain tumours which arise in combination with adenomatous polyposis are usually
      astrocytic tumours or medulloblastomas. An adult women with a pineoblastoma
      associated with familial adenomatous polyposis is presented. In regard to the
      neuro-epithelial origin of this tumour we propose that it should be included in
      the second category of brain tumour polyposis syndrome.

PMID- 10070472
TI  - Transient peduncular hallucinations secondary to brain stem compression by a
      cerebellar pilocytic astrocytoma.
AB  - Almost all peduncular hallucinations have been described in patients with
      intrinsic lesions of the midbrain. An, as yet, unreported case of peduncular
      hallucinosis caused by posterior compression of the midbrain by a cerebellar
      pilocytic astrocytoma is described. The hallucinations and associated symptoms
      only ceased after removal of the tumour.

PMID- 10070473
TI  - Argyrophilic nucleolar organizer region proteins (AgNORs) as an index of clinical
      and radiological invasiveness in pituitary adenomas.
AB  - Sixty-eight patients with pituitary adenomas were classified into groups based on
      their invasiveness and functional status. Mean argyrophilic nucleolar organizer
      region proteins (AgNOR) counts obtained from 200 cells showed no correlation with
      the invasive status of pituitary adenomas. However, the functional tumours showed
      significantly higher AgNOR counts than non-functional tumours.

PMID- 10070474
TI  - Pulmonary miliary tuberculosis with multiple intracerebral tuberculous granulomas
      -report of two cases.
AB  - Although intracerebral tuberculomas are common in countries where tuberculosis is
      still endemic, miliary tuberculosis with involvement of the central nervous
      system is exceptionally rare. We report two cases of pulmonary miliary
      tuberculosis with multiple intracerebral tuberculomas.

PMID- 10070475
TI  - Aneurysm occurring within a meningioma: case report.
AB  - Aneurysms can be expected to be found in approximately 0.5% of patients with
      brain tumours; nevertheless, the real incidence is difficult to assess because
      angiography is now seldom performed for brain tumours. In the literature, 42
      cases of meningioma associated with aneurysms are reported, but in none was the
      aneurysm intratumoural. We describe a case of intracranial meningioma with an
      intratumoural aneurysm in a 48-year-old woman.

PMID- 10070476
TI  - Spontaneous cerebrospinal fluid (CSF) rhinorrhoea in spongiform dysplasia of the
      cranium: an unusual presentation of neurofibromatosis.
AB  - A 20-year-old woman with neurofibromatosis presented with CSF rhinorrhoea.
      Spongiform dysplasia of the cranium was found. The dysplastic bone contained CSF.
      The exact site of the CSF fistula into the calvarium and into the paranasal
      sinuses could not be detected on investigation but nasal packing of the ethmoid
      and sphenoid sinuses controlled the rhinorrhoea. The unique features of this case
      are presented along with a brief review of the literature.

PMID- 10070477
TI  - Operative treatment of cervical spondylosis.

PMID- 10070478
TI  - "The pallidotomy debate": are micro-electrode-guided pallidotomies always located
      in the pallidum?

PMID- 10070479
TI  - A Quebec quencher.

PMID- 10070480
TI  - The role of oxidative stress in the genesis of heart disease.
AB  - Although researchers in radiation and cancer biology have known about the
      existence of free radicals and their potential role in pathobiology for several
      decades, cardiac biologists only began to take notice of these noxious species in
      the 1970s. Exponential growth of free radical research occurred after the
      discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible
      for the dismutation of superoxide radical--a free radical chain initiator. A fine
      balance between free radicals and a variety of endogenous antioxidants is
      believed to exist. Any disturbance in this equilibrium in favour of free radicals
      causes an increase in oxidative stress and initiates subcellular changes leading
      to cardiomyopathy and heart failure. Our knowledge about the role of free
      radicals in the pathogenesis of cardiac dysfunction is fast approaching the point
      where newer therapies employing antioxidants are in sight.

PMID- 10070481
TI  - Is the slowly activating component of the delayed rectifier current, IKs' absent
      from undiseased human ventricular myocardium?

PMID- 10070482
TI  - Serotonin, I(f) and human atrial arrhythmia.

PMID- 10070483
TI  - Prostaglandin--a pluralistic hormone embracing divergent signal properties.

PMID- 10070484
TI  - Congestive heart failure: role of cross-bridge cycle kinetics.

PMID- 10070485
TI  - Damage-induced arrhythmias: reversal of excitation-contraction coupling.

PMID- 10070486
TI  - Recent advances in cardiovascular development: promise for the future.

PMID- 10070487
TI  - The heart remembers.

PMID- 10070488
TI  - Ryanodine and the left ventricular force-interval and relaxation-interval
      relations in closed-chest dogs: insights on calcium handling.
AB  - OBJECTIVE: Although the myocardial force-interval and relaxation-interval
      relations are considered to be mechanical expressions of myocardial Ca2+
      handling, correlation of these phenomena with altered Ca2+ kinetics in the intact
      state is limited. Thus, I sought to determine the impact of selective impairment
      of physiologic sarcoplasmic reticulum Ca2+ release, achieved by the use of the
      drug ryanodine, on these relations in the intact animal. METHODS: Twelve dogs
      instrumented with left ventricular manometers and piezoelectric dimension
      crystals were studied before and after ryanodine (4 micrograms/kg intravenously).
      End-systolic elastance was measured at paced heart rates of 120-180 bpm to
      determine the force-frequency response. Mechanical restitution and relaxation
      restitution were determined by measuring contractile (single beat elastance) and
      relaxation (peak negative dP/dt) responses for beats delivered at graded
      extrasystolic intervals, with normalized responses expressed as a function of
      extrasystolic interval. RESULTS: Ryanodine accelerated mechanical restitution
      (time constant 60.3 +/- 3.9 versus 81.7 +/- 10.1 ms, p < 0.05) and reduced
      maximal contractile response (107.5 +/- 2.1 versus 122.1 +/- 5.7%, p < 0.05),
      slowed early relaxation restitution (time constant 65.5 +/- 13.8 versus 36.8 +/-
      3.8 ms, p < 0.05) without changing late relaxation restitution kinetics, and
      amplified the force-frequency response (end-systolic elastance, 180 bpm, 19.4 +/-
      4.3 versus 11.4 +/- 1.2 mm Hg/ml, p < 0.05). CONCLUSIONS: These findings suggest
      that in the intact animal, Ca2+ handling by the sarcoplasmic reticulum is a
      primary determinant of mechanical restitution and early relaxation restitution,
      but not late relaxation restitution. Conversely, ryanodine induced augmentation
      of the force-frequency response indicates a central role for sarcolemmal Ca2+
      influx in producing frequency potentiation.

PMID- 10070489
TI  - Regional electrophysiological effects of hypokalaemia, hypomagnesaemia and
      hyponatraemia in isolated rabbit hearts in normal and ischaemic conditions.
AB  - OBJECTIVE: The aims of this study were to establish an isolated working heart
      model for electrophysiological recordings from the epicardium and endocardium and
      to examine regional effects of changes in ion concentrations in normal and
      ischaemic conditions. METHODS: Monophasic action potential duration (MAPD90),
      effective refractory period (ERP) and conduction delay were measured
      simultaneously in the epicardium and endocardium of rabbit hearts paced at 3.3
      Hz, subjected to 30 min of regional ischaemia and 15 min of reperfusion. The
      hearts were exposed before and throughout ischaemia and reperfusion to
      hypokalaemia (K+ = 2 mM), hypomagnesaemia (Mg2+ = 0.5 mM) or hyponatraemia (Na+ =
      110 mM). RESULTS: In the control hearts, no regional electrophysiological
      differences were seen before ischaemia, but ischaemia-induced MAPD90 shortening
      and postrepolarisation refractoriness were greater in the epicardium than in the
      endocardium and conduction delay increased only in the epicardium. Hypokalaemia
      shortened ERP in the epicardium (but not endocardium) and increased conduction
      delay in all areas before ischaemia, but it had no effects during ischaemia.
      During reperfusion hypokalaemia increased the incidence of recurrent
      tachyarrhythmias. Hypomagnesaemia had no effect before ischaemia, increased
      epicardial (but not endocardial) MAPD90 shortening during ischaemia, although it
      had no pro-arrhythmic action. Hyponatraemia increased conduction delay in all
      areas before ischaemia and produced asystole or severe bradycardia in all hearts.
      During ischaemia, hyponatraemia decreased ERP shortening and inducibility of
      arrhythmias in the epicardium (but not endocardium). CONCLUSIONS: We conclude
      that the more pronounced effect of ischaemia upon the epicardium than the
      endocardium can be explained by the contact of the endocardium with intracavitary
      perfusate. We also conclude that changes in ion concentrations may have
      differential regional electrical effects in normal or ischaemic conditions.

PMID- 10070490
TI  - Myocardial temperature reduction attenuates necrosis after prolonged ischemia in
      rabbits.
AB  - OBJECTIVE: Previously we observed that a large reduction in infarct size was
      attained by cooling the risk region of the heart, either before or early after
      the onset of a 30-min coronary artery occlusion. While this is a standard
      duration of ischemia used in the rabbit model of infarction, it may not reflect
      the situation of patients who are reperfused late. The effects of regional
      hypothermia with a longer duration of ischemia, and when the intervention is
      applied later, are unknown. This study tests the hypothesis that a local
      reduction in cardiac temperature protects myocardium during prolonged ischemia (2
      h) even if begun well after coronary artery occlusion. METHODS: Anesthetized
      rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits
      were randomly assigned to a treated group: topical myocardial cooling starting 30
      min after coronary occlusion (n = 14), or control group, no intervention (n =
      12). Myocardial temperature in the risk zone, hemodynamics and regional
      myocardial blood flow were measured. RESULTS: Ischemic zone temperature was
      similar in both groups at 30 min post occlusion, but the cooling maneuver
      produced a reduction in temperature in the risk region of the treated group such
      that myocardial temperature was reduced an average of 10 degrees C between 30 and
      60 min of coronary artery occlusion. Myocardial temperature in the control group
      remained within 0.3 degree C of baseline during coronary artery occlusion and
      into reperfusion. Core temperatures were similar in both groups. Hemodynamic
      parameters and collateral blood flow during occlusion were also equivalent in
      both groups. After 120 min of coronary occlusion, necrosis in the control group
      comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts,
      infarct size, expressed as a fraction of the risk region was significantly lower.
      Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs.
      controls), and thus cooling resulted in a salvage of approximately 18% of the
      risk region. CONCLUSION: These results show that reducing myocardial temperature
      protects ischemic myocardium during a long duration of ischemia even if initiated
      after coronary artery occlusion.

PMID- 10070491
TI  - Delayed rectifier potassium current in undiseased human ventricular myocytes.
AB  - OBJECTIVE: The purpose of the study was to investigate the properties of the
      delayed rectifier potassium current (IK) in myocytes isolated from undiseased
      human left ventricles. METHODS: The whole-cell configuration of the patch-clamp
      technique was applied in 28 left ventricular myocytes from 13 hearts at 35
      degrees C. RESULTS: An E-4031 sensitive tail current identified the rapid
      component of IK (IKr) in the myocytes, but there was no evidence for an E-4031
      insensitive slow component of IK (IKs). When nifedipine (5 microM) was used to
      block the inward calcium current (ICa), IKr activation was fast (tau = 31.0 +/-
      7.4 ms, at +30 mV, n = 5) and deactivation kinetics were biexponential and
      relatively slow (tau 1 = 600.0 +/- 53.9 ms and tau 2 = 6792.2 +/- 875.7 ms, at 
      40 mV, n = 7). Application of CdCl2 (250 microM) to block ICa altered the voltage
      dependence of the IKr considerably, slowing its activation (tau = 657.1 +/- 109.1
      ms, at +30 mV, n = 5) and accelerating its deactivation (tau = 104.0 +/- 18.5 ms,
      at -40 mV, n = 8). CONCLUSIONS: In undiseased human ventricle at 35 degrees C IKr
      exists having fast activation and slow deactivation kinetics; however, there was
      no evidence found for an expressed IKs. IKr probably plays an important role in
      the frequency dependent modulation of repolarization in undiseased human
      ventricle, and is a target for many Class III antiarrhythmic drugs.

PMID- 10070492
TI  - Effect of 5-HT4 receptor stimulation on the pacemaker current I(f) in human
      isolated atrial myocytes.
AB  - OBJECTIVE: 5-HT4 receptors are present in human atrial cells and their
      stimulation has been implicated in the genesis of atrial arrhythmias including
      atrial fibrillation. An I(f)-like current has been recorded in human atrial
      myocytes, where it is modulated by beta-adrenergic stimulation. In the present
      study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on
      I(f) electrophysiological properties, in order to get an insight into the
      possible contribution of I(f) to the arrhythmogenic action of 5-HT in human
      atria. METHODS: Human atrial myocytes were isolated by enzymatic digestion from
      samples of atrial appendage of patients undergoing coeffective cardiac surgery.
      Patch-clamped cells were superfused with a modified Tyrode's solution in order to
      amplify I(f) and reduce overlapping currents. RESULTS AND CONCLUSIONS: A time
      dependent, cesium-sensitive increasing inward current, that we had previously
      described having the electrophysiological properties of the pacemaker current
      I(f), was elicited by negative steps (-60 to -130 mV) from a holding potential of
      -40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of 
      88.9 +/- 2.6 mV (n = 14). 5-HT (1 microM) consistently caused a positive shift of
      V1/2 of 11.0 +/- 2.0 mV (n = 8, p < 0.001) of the activation curve toward less
      negative potentials, thus increasing the amount of current activated by clamp
      steps near the physiological maximum diastolic potential of these cells. The
      effect was dose-dependent, the EC50 being 0.14 microM. Maximum current amplitude
      was not changed by 5-HT. 5-HT did not increase I(f) amplitude when the current
      was maximally activated by cAMP perfused into the cell. The selective 5-HT4
      antagonists, DAU 6285 (10 microM) and GR 125487 (1 microM), completely prevented
      the effect of 5-HT on I(f). The shift of V1/2 caused by 1 microM 5-HT in the
      presence of DAU 6285 or GR 125487 was 0.3 +/- 1 mV (n = 6) and 1.0 +/- 0.6 mV (n
      = 5), respectively (p < 0.01 versus 5-HT alone). The effect of 5-HT4 receptor
      blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect
      of 1 microM isoprenaline on I(f). Thus, 5-HT4 stimulation increases I(f) in human
      atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT
      in human atrium.

PMID- 10070493
TI  - An inhibitor of nitric oxide synthase does not increase contraction or beta
      adrenoceptor sensitivity of ventricular myocytes from failing human heart.
AB  - OBJECTIVE: Nitric oxide (NO) has been implicated in the depression of cardiac
      function in human heart failure. Some reports have identified iNOS (inducible
      nitric oxide synthase) within the myocyte component of the failing human heart,
      and NO is known to decrease the contraction amplitude of isolated ventricular
      myocytes. We have treated myocytes from failing human ventricle with a NOS
      inhibitor, NG-monomethyl-L-arginine (L-NMMA), in an attempt to restore
      contractile function. METHODS AND RESULTS: Myocytes were isolated from failing
      and non-failing human ventricles and their contraction amplitude was measured
      during superfusion (32 degrees C, 1-2 mmol/l Ca2+) and electrical stimulation
      (0.1-2 Hz). The contraction amplitude of myocytes from failing hearts was
      depressed in a frequency-dependent manner. At 1 Hz, the contraction amplitude of
      cells from non-failing heart was 4.70 +/- 0.53% cell shortening (mean +/- SEM, n
      = 13 subjects), compared with 2.18 +/- 0.27% (P < 0.01, 11 patients) from
      patients with ischaemic heart disease (IHD) or 2.56 +/- 0.74% (P < 0.02, six
      patients) with dilated cardiomyopathy (DCM). Superfusion with 0.1 mmol/l L-NMMA
      did not increase contraction amplitude in myocytes from failing heart at either
      0.2 Hz (n = 11) or 1 Hz (n = 7). Responses to beta-adrenoceptor stimulation were
      reduced in myocytes from failing human heart, with contraction amplitude in
      maximum isoprenaline 0.47 +/- 0.11 of that in high Ca2+ in the same cell (n = 6),
      compared to 0.99 +/- 0.07 in non-failing heart (n = 14, P < 0.01). The presence
      of 0.1 mmol/l L-NMMA did not increase the isoprenaline/Ca2+ ratio in myocytes
      from failing heart (0.40 +/- 0.09, P = NS). CONCLUSION: These results do not
      suggest a functional role for tonic NO production in the frequency-dependent
      depression of contraction or beta-adrenoceptor desensitisation in myocytes from
      failing human ventricle.

PMID- 10070494
TI  - Gene expression in rod shaped cardiac myocytes, sorted by flow cytometry.
AB  - OBJECTIVE: Primary cardiac myocyte cultures are usually contaminated with
      variable parts of different cell types, such as fibroblasts, endothelial cells
      and smooth muscle cells. Thus, the objective of our study was to analyse the gene
      expression in a pure population. METHODS: To obtain an homogeneous population,
      cardiac myocytes from adult rats were fixed with ethanol and sorted by flow
      cytometry. This approach is suitable for isolating either single cells or up to
      several thousand cells. To measure the messenger ribonucleic acid (mRNA)
      expression of different genes at the level of a few rod-shaped myocytes, a cDNA
      library was created by polymerase chain reaction (PCR). RESULTS: Sorting by a
      fluorescence-activated cell sorter (FACS) resulted in pure rod-shaped cardiac
      myocytes and isolated RNA from these cells is undegraded, as shown by Northern
      blotting. We demonstrated both the expression of housekeeping genes, such as beta
      actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as well as the myocyte
      specific transcripts, alpha-cardiac myosin heavy chain (alpha-MHC) and beta-MHC.
      Furthermore, we showed the induction of the immediately early gene c-fos at the
      level of ten sorted cells. CONCLUSIONS: This method allows one to study gene
      expression in different cell types within the heart, in tissue samples or to
      tackle the problem of heterogeneity within a cell population.

PMID- 10070495
TI  - Effects of prostaglandin F2 alpha on intracellular pH, intracellular calcium,
      cell shortening and L-type calcium currents in rat myocytes.
AB  - OBJECTIVE: We have studied the mechanisms underlying the positive inotropic
      action of prostaglandin F2 alpha (PGF2 alpha) by monitoring intracellular calcium
      transients, intracellular pH, L-type calcium currents and cell shortening in
      isolated ventricular myocytes. METHODS: Rat myocytes were loaded with fura-2AM
      for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell
      shortening was recorded using an edge detection system, and L-type calcium
      currents measured using whole cell patch clamping. RESULTS: PGF2 alpha (3 nmol l
      1-3 mumol l-1 increased single myocyte shortening and reduced resting cell length
      in a concentration-dependent manner. While myocyte shortening was increased by
      PGF2 alpha, this was not associated with any change in the amplitude of
      intracellular calcium transients, diastolic calcium, or L-type calcium currents.
      However, the same myocytes were capable of responding to catecholamines with
      increases in calcium transient amplitude and L-type calcium currents. PGF2 alpha
      (3 mumol l-1 caused a reversible rise in intracellular pH of 0.08 +/- 0.01 pH
      units (n = 5, p < 0.05). The Na(+)-H+ exchanger inhibitor, HOE 694 (10 mumol l-1,
      abolished the PGF2 alpha-induced rise in pH and the increase in cell shortening.
      PGF2 alpha-induced increases in cell shortening and intracellular pH were also
      attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 mumol l-1.
      CONCLUSION: The positive inotropic action of PGF2 alpha appears to be mediated
      via activation of the Na(+)-H+ exchanger with the possible involvement of PKC.
      This suggests that PGF2 alpha-produces intracellular alkalosis, which then
      sensitizes cardiac myofilaments to calcium.

PMID- 10070496
TI  - Effect of bolus epinephrine on systemic hemodynamics in canine anaphylactic
      shock.
AB  - OBJECTIVE: Epinephrine (Epi) is considered to be the drug of choice for
      anaphylactic shock (AS). However, the benefit of this drug on improving systemic
      hemodynamics in AS has never been shown. We used a canine ragweed model of AS to
      determine if an intravenous bolus of Epi hastened the recovery of hemodynamics
      and modified mediator release (Med) compared with no treatment (NT). METHODS: In
      one protocol (n = 8), the effects on hemodynamics of two intravenous doses of Epi
      (0.01 and 0.025 mg/kg) were examined for 3 h postshock in respective studies
      approximately three weeks apart under pentobarbital anesthesia in the same
      animal. In five other dogs, left ventricular (LV) mechanics were additionally
      determined by sonomicrometric techniques to determine changes in contractility as
      defined by the preload recruitable stroke-work (SW) relationship. RESULTS:
      Compared with NT values, Epi treatments produced only transient increases in mean
      arterial pressure (MAP) and cardiac output (CO) post-challenge. By 20 min
      postshock, CO in the Epi studies were generally lower (p < 0.05) and BP was not
      different from NT values. With Epi treatment, SW was reduced for a given LV end
      diastolic volume compared with the control study. Epi treatments also caused
      relatively higher plasma thromboxane B2 concentrations postshock. CONCLUSION: Our
      findings indicate that, when given immediately postshock, bolus-Epi did not
      hasten recovery and caused impairment in LV mechanics in canine AS.

PMID- 10070497
TI  - Morphine preconditioning attenuates neutrophil activation in rat models of
      myocardial infarction.
AB  - Previous results from our laboratory have suggested that morphine can attenuate
      neutrophil activation in patients with acute myocardial infarction. To elucidate
      if morphine preconditioning (PC) has the same effects via activation of
      neutrophil endopeptidase 24.11 (NEP), we measured serum levels of intercellular
      adhesion molecule-1 (ICAM-1), gp100MEL14 and NEP in adult Wistar rats subjected
      to ten different protocols (n = 10 for each) at baseline, immediately after and 2
      h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of
      reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions
      (100 micrograms/kg) interspersed with 5-min drug-free periods before the
      prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at
      risk (AAR), was determined by triphenyltetrazolium staining. Pretreatment with
      morphine increased NEP activities (9.86 +/- 1.98 vs. 5.12 +/- 1.10 nmol/mg
      protein in control group; p < 0.001). Naloxone (mu-opioid receptor antagonist)
      (4.82 +/- 1.02 nmol/mg protein) and phosphoramidon (NEP inhibitor) (4.66 +/- 1.00
      nmol/mg protein) inhibited morphine-activated NEP, whereas glibenclamide (ATP
      sensitive potassium channel antagonist) and chelerythrine (protein kinase C
      inhibitor) had no effects. The ICAM-1 and gp100MEL14 of the third sampling were
      lowest for those with morphine PC (280 +/- 30 ng/ml and 2.2 +/- 0.7
      micrograms/ml; p < 0.001), but naloxone (372 +/- 38 ng/ml and 3.8 +/- 0.9
      micrograms/ml) and phosphoramidon (382 +/- 40 ng/ml and 4.2 +/- 1.1
      micrograms/ml) abolished the above phenomenon. IS/AAR were definitely lowest for
      those with morphine PC (24 +/- 7%; p < 0.05). Morphine preconditioning increases
      NEP activities to attenuate shedding of gp100MEL14 and to ICAM-1 and, thus,
      provides myocardial protection.

PMID- 10070498
TI  - Identification of phospholipase C beta isoforms and their location in cultured
      vascular smooth muscle cells of pig, human and rat.
AB  - OBJECTIVES: Four phospholipase C (PLC) beta isoforms have been described in pig
      aortic vascular smooth muscle. The aim was to determine if all four PLC beta
      isoforms are commonly expressed in vascular smooth muscle cells (VSMC) of three
      species, i.e. pig, human and rat, and if the individual isoforms had distinctive
      intracellular distributions. METHODS: Vascular smooth muscle cell cultures were
      derived from explants of porcine and rat aorta and a human renal artery cell
      line. PLC beta isoform content was resolved using Western blotting. Intracellular
      location was determined by immunocytochemistry and confocal microscopy. RESULTS:
      All three species expressed PLCs, beta 1, beta 2, beta 3 and beta 4. In all
      species, PLC beta 1 demonstrated foci of concentration throughout the cytoplasm;
      PLC beta 2 demonstrated a punctate pattern that was principally at the cell
      periphery or was in the Golgi, depending upon the antibody used; PLC beta 3 was
      also cytoplasmic but showed a different pattern from PLC beta 1 and PLC beta 4
      was cytoplasmic, except in pig quiescent cells, where it was associated with
      filamentous structures at the intersection with the plasma membrane. CONCLUSIONS:
      VSMCs of three different species express all four PLC beta isoforms. Each isoform
      has a unique and consistent signature of distribution that is generally common to
      all species.

PMID- 10070499
TI  - Kinins modulate the sodium-dependent autoregulation of renal medullary blood
      flow.
AB  - OBJECTIVE: In the recent past it has become clear that the kallikrein-kinin
      system is closely intertwined with long-term blood pressure regulation. It was
      shown that a kinin B2 receptor blockade leads to a sodium-dependent rise in blood
      pressure. The underlying mechanisms of this phenomenon, however, remain unclear.
      The osmotic gradient of the renal medulla is a prerequisite for the preservation
      of volume and sodium by the kidney. We thus hypothesized, that a kinin dependent
      modulation of medullary blood flow accounts for the influence of sodium on blood
      pressure. METHODS: In 39 urethane anaesthetized rats pressure dependent
      regulation of whole kidney blood flow and cortical and medullary blood flow were
      estimated via laser-Doppler flux by a stepwise reduction of renal perfusion
      pressure to 30 mm Hg. RESULTS: In controls (n = 15), a reduction in renal
      perfusion pressure to 30 mm Hg lead to a concomitant reduction in whole kidney
      blood flow (25 +/- 3% of baseline) and cortical laser-Doppler flux (36 +/- 5% of
      baseline). In contrast, medullary laser-Doppler flux decreased only to 79 +/- 8%
      of the baseline level. Providing a 2% sodium chloride solution as drinking water
      over 5 days (n = 12), resulted in a significantly lower capability to
      autoregulate medullary flow (50 +/- 6% of baseline, P < 0.05). Acute subcutaneous
      administration of Hoe 140, a bradykinin B2 receptor antagonist (300 micrograms/kg
      bwt), restored autoregulation of medullary flow to almost normal levels (93 +/-
      12% of baseline, P < 0.01 versus high sodium diet alone, n = 12). CONCLUSIONS:
      Our results indicate that B2 receptor blockade restores the attenuated
      autoregulation of medullary Doppler flux during sodium enriched diet. This,
      suggests that the kinin dependent impact of sodium on blood pressure regulation
      is mediated by modulations of medullary blood flow autoregulation.

PMID- 10070500
TI  - Alterations of cross-bridge kinetics in human atrial and ventricular myocardium.
AB  - CONDENSED ABSTRACT: We analyzed actomyosin cross-bridge kinetics in human atrial
      and ventricular muscle strip preparations by using sinusoidal length changes from
      0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in
      ventricular human myocardium and lower in failing than in non-failing left
      ventricular human myocardium. beta-Adrenergic stimulation increased the minimum
      stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are
      temperature-dependent, with a Q10 of at least 2.7. BACKGROUND: Dynamic stiffness
      measurements have revealed acute and chronic alterations of actomyosin cross
      bridge kinetics in cardiac muscles of a variety of different animal species. We
      studied dynamic stiffness in right atrial and left ventricular preparations of
      non-failing and failing human hearts and tested the influence of the temperature
      and beta-adrenergic stimulation on cross-bridge kinetics. METHODS AND RESULTS:
      Muscle strips were prepared from right atria and left ventricles from human non
      failing and failing hearts. After withdrawal of calcium, steady contracture
      tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length
      oscillations of 1% muscle length were applied, with a frequency spectrum of
      between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change
      and the corresponding force response amplitude. The specific minimum stiffness
      frequency, which indicates the interaction between cross-bridge recruitment and
      cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum
      stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80
      +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The
      minimum stiffness frequency was 41% higher in non-failing compared to failing
      left ventricular human myocardium. (3) Over a wide range of experimental
      temperatures, the minimum stiffness frequency changed, with a Q10 of at least
      2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the
      minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05)
      lowered contracture tension by 7 +/- 1%. CONCLUSIONS: The contractility of human
      heart muscle is not only regulated by excitation-contraction coupling but also by
      modulation of intrinsic properties of the actomyosin system. Acute and chronic
      alterations of cross-bridge kinetics have been demonstrated, which play a
      significant role in the physiology and pathophysiology of the human heart.

PMID- 10070501
TI  - Neurocardiac and cerebral responses evoked by esophageal vago-afferent
      stimulation in humans: effect of varying intensities.
AB  - OBJECTIVE: This study was designed to determine whether esophageal vago-afferent
      electrostimulation, over a wide range of stimulus intensities, can sustain a
      cardiac vago-efferent effect by way of central nervous system processing.
      METHODS: Studies were performed in ten healthy male subjects (23.9 +/- 6.3
      years). Esophageal electrostimulation was carried out using a stimulating
      electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent
      fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128
      s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate
      autospectra and cerebral evoked potentials were recorded at baseline and at each
      stimulus intensity in random order. RESULTS: With esophageal electrical
      stimulation, we observed a small non-significant decrease in heart rate. There
      was a dramatic shift of the instantaneous heart rate power spectra towards
      enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect
      was sustained throughout all intensities with no further change in either the low
      frequency or high frequency power. Conversely, there was a linear dose response
      relationship between cerebral evoked potential amplitude and stimulus intensity
      mainly occurring above perception threshold (10 mA). Esophageal stimulation had
      no significant effect on heart rate or respiratory frequency at any stimulus
      intensity. CONCLUSIONS: These results indicate that electrical stimulation of the
      distal esophagus across a wide range of current intensities elicits a
      reproducible shift in the heart rate power spectrum towards enhanced vagal
      modulation. The data suggest a closed loop afferent/efferent circuitry wherein
      tonic visceral afferent impulses appear to elicit a phasic or modulatory vago
      efferent cardiac response in healthy subjects.

PMID- 10070502
TI  - Endothelial function is impaired in fit young adults of low birth weight.
AB  - OBJECTIVE: Non-insulin-dependent diabetes, hypertension and ischaemic heart
      disease, with insulin resistance, are associated with low birth weight (the
      'Small Baby Syndrome'). Common to these adult clinical conditions is endothelial
      dysfunction. We tested the hypothesis that endothelial dysfunction could precede
      their development in those of low birth weight. METHODS: Endothelial function was
      measured by ultrasonic 'wall-tracking' of flow-related brachial artery dilatation
      in fit 19-20 year old subjects randomly selected (blind to the investigators
      throughout the study) from low (< 2.5 kg) and normal (3.0-3.8 kg) birth weight
      subjects in the 1975-7 cohort of the Cardiff Births Survey and with no known
      cause for endothelial dysfunction. RESULTS: Flow-related dilatation was impaired
      in low birth weight relative to normal birth weight subjects (median 0.04 mm
      [1.5%] [n = 22] cf. 0.11 mm [4.1%] [n = 17], p < 0.05; 0.04 mm [1.5%] [n = 15]
      cf. 0.12 mm [4.4%] [n = 12], p < 0.05 after exclusion of inadvertently included
      ever-smokers). CONCLUSION: The findings suggest that endothelial dysfunction is a
      consequence of foetal malnutrition, consistent with contributing to the clinical
      features of the 'Small Baby Syndrome' in later adult life.

PMID- 10070503
TI  - Suprachoroidal haemorrhage.

PMID- 10070504
TI  - Posterior uveitis: new insights provided by indocyanine green angiography.

PMID- 10070505
TI  - Indocyanine green angiography in inflammatory eye disease.
AB  - PURPOSE: The choroid plays an integral role in the evolution of a number of
      inflammatory eye diseases but only limited information is provided on the
      choroidal vasculature by fluorescein angiography. METHODS: This study used
      indocyanine green (ICG) videoangiography to assess the degree of choroidal
      vascular involvement in inflammatory eye diseases and the results obtained were
      compared with fluorescein angiography. RESULTS: A total of 34 patients were
      examined: 6 with retinal vasculitis and 28 with chorioretinitis of various
      aetiologies. Areas of active involvement of the choroid were seen as areas of
      hypofluorescence on ICG angiography, representing areas of inflammatory
      infiltrate and/or choroidal hypoperfusion. No leakage of ICG occurred from large
      choroidal vessels at any stage in any disease. In contrast to sodium fluorescein,
      there was no leakage of ICG from retinal vessels in active inflammation. An
      inflammatory choroidal neovascular membrane leaked fluorescein and fluoresced
      late with ICG. CONCLUSION: ICG videoangiography provides useful information on
      the degree of choroidal involvement in inflammatory eye disease and is a valuable
      adjunct to fluorescein angiography.

PMID- 10070506
TI  - Surgical excision of subfoveal neovascular membranes.
AB  - BACKGROUND: Subfoveal choroidal neovascular membranes (CNV) are a cause of
      significant visual impairment. Laser treatment of such lesions results in visual
      loss. Surgical excision of CNV may allow stabilisation or improvement of vision.
      A series of results of surgical excision are presented. METHODS: The records for
      43 eyes of 40 consecutive patients undergoing surgical excision of CNV not
      associated with age-related macular degeneration (AMD) were reviewed
      retrospectively. Statistical analyses of the relationship between pre-operative
      factors and post-operative visual results were made. Improvement or worsening of
      visual acuity was defined as a change of more than 2 lines of Snellen acuity.
      RESULTS: In 79.1% of patients visual acuity was improved or unchanged following
      surgery, and in 20.9% there was a reduction of Snellen acuity. There was no
      statistically significant association between visual outcome and age, gender,
      duration of visual symptoms, cause of CNV, presence of subretinal haemorrhage,
      elevation of retina by subretinal fluid, prior laser surgery, or the presence of
      pre-operative or intraoperative subretinal haemorrhage. There was a possible
      association between the non-use of gas tamponade and an increased chance of
      reduced vision. Visual loss was more likely in those eyes with good pre-operative
      visual acuity. Recurrence of CNV was noted in 10 (23%) eyes; repeat surgery was
      not associated with a worse visual outcome. CONCLUSIONS: Surgical excision of CNV
      not related to AMD is a promising technique. More meaningful assessment of visual
      function in these patients will allow refinement of case selection.

PMID- 10070507
TI  - Surgical removal of non-age-related subfoveal choroidal neovascular membranes.
AB  - PURPOSE: To assess anatomical and visual results following the surgical removal
      of non-age-related subfoveal choroidal neovascular membranes. METHODS: A
      retrospective study was carried out of 31 consecutive patients undergoing
      vitrectomy, parafoveal retinotomy and removal of subfoveal choroidal neovascular
      membranes that were either idiopathic or associated with multifocal choroiditis,
      high myopia, trauma or angioid streaks. RESULTS: Visual acuity improved or
      remained the same in 25 eyes (81%) after a mean follow-up of 10.1 months (range 3
      37 months). visual acuity improved by more than 2 lines of Snellen acuity in 5
      eyes (16%) and decreased by more than 2 lines in 2 eyes (6%). There was no
      significant association between the final visual outcome and length of symptoms
      prior to surgery or pre-operative visual acuity. Atrophy of the retinal pigment
      epithelium and older age were associated with poor outcome. Membranes recurred in
      11 eyes (35%), and eyes with subfoveal blood prior to surgery were more likely to
      have recurrent membranes. CONCLUSIONS: The results of surgical removal of non-age
      related subfoveal neovascular membranes have been encouraging, but further
      studies of long-term outcome and of the natural history of individual conditions
      are required.

PMID- 10070508
TI  - Delays in the diagnosis of uveal melanoma and effect on treatment.
AB  - PURPOSE: To investigate the mode of presentation of uveal melanomas, delays in
      their diagnosis and the effect of delayed diagnosis on treatment outcome.
      METHODS: An analysis was carried out of 50 consecutive patients undergoing
      treatment for uveal melanoma at the Ocular Oncology Service in Liverpool. The
      mode of presentation of the tumour, onset of symptoms and subsequent management
      were determined by interview at the time of treatment. RESULTS: Seventy-two per
      cent of patients had one or more symptoms directly attributable to the tumour.
      These included blurred vision (36%), photopsia (22%), visual field loss (16%),
      floaters (4%) and metamorphopsia (4%). Forty-two per cent of patients experienced
      delays in the diagnosis and treatment due to misdiagnoses such as macular
      degeneration and naevus or due to the lesion being missed at the initial visit.
      Patients who had experienced delays in diagnosis received treatment after a mean
      of 6.6 months compared with 4.2 weeks for those who did not experience any delay
      (p = 0.003). Such patients were more likely to be treated by enucleation (52% vs
      17%, p = 0.008) than by an eye-conserving method such as radiotherapy or trans
      scleral local resection. CONCLUSIONS: The primary aim of treatment of uveal
      melanoma is to reduce the risk of death from metastases and a secondary aim is to
      conserve the eye with as much vision as possible. This study identifies common
      reasons for delays in the diagnosis of uveal melanoma. While the effect of early
      treatment on survival remains controversial, this study shows that patients who
      have their tumours diagnosed promptly are more likely to be treated by an eye
      conserving method than by enucleation.

PMID- 10070509
TI  - The role of azathioprine in the management of retinal vasculitis.
AB  - PURPOSE: Azathioprine is commonly used as a second-line immunosuppressive agent
      in the management of patients with retinal vasculitis. The aim of this study was
      to determine the efficacy of azathioprine by evaluating its effect on relapse
      rate, clinical outcome and maintenance steroid dose. METHODS: A retrospective
      analysis was performed of 34 patients presenting over 15 years to the Medical Eye
      Unit at St Thomas Hospital. Relapse rate, steroid dosage, inflammatory score and
      visual acuity were assessed before and during treatment with azathioprine.
      RESULTS: Thirty-four patients (23 male) aged 17-70 years (median 41.4, median 38)
      were enrolled. Fifteen had idiopathic retinal vasculitis, 12 had Behcet's
      disease, 2 sarcoidosis, 2 sympathetic ophthalmia, 1 birdshot retinochoriodopathy,
      1 Still's disease and 1 Harada's disease. The principal indications for
      azathioprine treatment were uncontrolled disease despite appropriate steroid
      therapy in 28 patients (82%) or to permit a decrease in steroid dosage in 6
      patients (18%). Frequency of relapse was assessed in 10 patients whose pre
      treatment and treatment periods with azathioprine were of 1 year or greater. All
      were found to have a decreased relapse rate. In 60%, reduction of steroid dosage
      was achieved. Ocular inflammatory score decreased in 56% of eyes and visual
      acuity was improved or maintained in 64%. In 8 patients treatment had to be
      stopped due to side effects. CONCLUSION: Within the limitations of a
      retrospective study, we found azathioprine when used in combination with systemic
      steroids to be most effective at reducing the relapse rate of retinal vasculitis,
      but only partially effective in allowing a reduction in steroid dosage.

PMID- 10070510
TI  - Taping outpatient consultations: a survey of attitudes and responses of adult
      patients with ocular malignancy.
AB  - PURPOSE: To study the attitudes and responses of cancer patients to audiotaped
      consultations as a communication aid in an ophthalmic clinic. METHODS: Ninety
      four patients attending an ocular oncology clinic were given an audiotape of
      their initial consultation. They were then administered a structured interview
      with questionnaire regarding their views on the tape when they attended an
      outpatient clinic for follow-up after surgery or radiotherapy. RESULTS: 91% of
      patients had listened to the tape at least once, often prior to their treatment
      or follow-up visit. Most patients had shared the tape with immediate relatives,
      including their spouse (58%) or other family members (45%). Of those who had
      listened to the tape, 94% described it as very useful or quite useful in helping
      them understand their condition. The majority had found it valuable in helping
      them understand their treatment and its side-effects, in reducing their fears and
      anxieties and in their emotional and psychological adjustment to their illness.
      Most commented on the tape as a valuable communication aid to the consultation
      process. CONCLUSIONS: Taping of the consultation as a method of improving
      communication is popular among cancer patients. The vast majority benefit greatly
      from being able to hear their consultation again in their own time.

PMID- 10070511
TI  - Haemodynamic responses to subconjunctival mydriatic agents (Mydricaine) used for
      maintenance of perioperative mydriasis in patients undergoing vitreoretinal
      surgery.
AB  - PURPOSE: To assess the systemic effects of subconjunctival mydriatic agents
      (Mydricaine). METHODS: Haemodynamic variables were recorded at baseline and
      during the first 60 min following subconjunctival injection of Mydricaine and
      normal saline. RESULTS: Statistical analysis of the change in heart rate showed a
      highly significant difference between the two groups (p < 0.001). There was no
      significant difference in the effect on systolic or diastolic blood pressure
      between the two groups. CONCLUSIONS: We advise extreme caution when using
      Mydricaine via the subconjunctival route in patients with compromised cardiac
      function.

PMID- 10070512
TI  - Medical management of orbital myocysticercosis: a pilot study.
AB  - PURPOSE: To evaluate the efficacy of albendazole in the management of orbital
      myocysticercosis. METHOD: Twenty-one consecutive patients diagnosed as having
      orbital myocysticercosis by ultrasonography, supported by computed tomography
      (CT)/magnetic resonance imaging (MRI), were included in the study. All patients
      received oral albendazole at a dosage of 30 mg/kg for 15 days with a low-dose
      steroid cover (5-10 mg per day). The patients were followed on day 2 at 2 weeks,
      1 month, 3 months, 6 months and 9 months, and finally at 1 year. Orbital
      sonography was performed at 2 weeks, 3 months, 6 months, 9 months and 1 year. CT
      scan was performed at 6 months and 1 year. RESULTS: Orbital sonography revealed a
      well-defined cystic lesion with clear contents and a hyperechoic area suggestive
      of a scolex in all the patients. CT or MRI provided additional supportive
      evidence. The size of the cysts measured before treatment ranged from 6.2 to 13.4
      mm (mean 11.4 mm). Medial rectus was involved in 10 cases, superior rectus in 7
      cases and lateral rectus in 4 cases. Serial ultrasonography revealed a gradual
      reduction in the cyst size in 20 patients. A mild obscuration of the cyst wall,
      followed by collapse of the cyst cavity and obscuration of the scolex, were
      progressively seen as the cyst reduced in size. Complete resolution of the cyst
      was seen in all cases at 6 months. A CT scan performed at 1 year supported the
      ultrasonographic findings. No systemic side effects were noted. CONCLUSION: Oral
      albendazole appears to be highly efficacious in the management of orbital
      myocysticercosis.

PMID- 10070513
TI  - The incidence of diplopia following coronal and translid orbital decompression in
      Graves' orbitopathy.
AB  - PURPOSE: Firstly, to assess the incidence of induced diplopia following orbital
      decompression in patients with Graves' orbitopathy. Secondly, to assess patient
      satisfaction after orbital decompression. Thirdly, to determine the factors that
      contribute to the variable reported incidence of diplopia complicating
      decompression surgery. METHODS: We present a retrospective analysis of the
      alterations of ocular motility in a consecutive series of 81 patients with
      Graves' orbitopathy who underwent orbital decompression by either a coronal or a
      translid approach. We assessed patient satisfaction by a telephone survey, and we
      reviewed the literature. RESULTS: Eleven patients underwent decompressive surgery
      for dysthyroid optic neuropathy (DON); 5 of them had a three-wall coronal
      decompression, the other 6 had a two-wall translid decompression. One of the 5
      (20%) coronal versus 2 of the 6 (33%) traslid patients experienced worsening of
      their existing diplopia. Seventy patients underwent surgery for disfiguring
      proptosis; 41 of them had a coronal decompression and 29 had a translid
      decompression. Eight of the 41 coronal patients (20%) and 4 of the 29 translid
      patients (14%) experienced aggravation of their motility impairment. There was no
      statistically significant difference between these percentages (chi-squared, p >
      0.05). Three of 26 coronal patients (12%) without pre-operative motility
      impairment developed diplopia in all directions. Twenty-five per cent needed
      strabismus surgery (9% multiple times). High satisfaction scores were noted after
      both types of orbital decompression. Through a review of the literature, several
      factors that may add to heterogeneous results were identified, including
      definition of diplopia, inclusion criteria and type of surgery. CONCLUSIONS:
      Induced diplopia is seen after any type of orbital decompression (19% overall),
      and its incidence is determined by various factors. To facilitate comparative
      studies between decompression techniques, a standardised protocol for orthoptic
      evaluation should be developed.

PMID- 10070514
TI  - The contribution of macular changes to visual loss in benign intracranial
      hypertension.
AB  - PURPOSE: To describe the significance of macular changes to visual outcome in
      benign intracranial hypertension (BIH). METHOD: The clinical and photographic
      records of 24 patients with BIH who required optic nerve sheath fenestration were
      analysed. RESULTS: Macular changes were found in 21 of 48 (44%) eyes. These were:
      choroidal folds 9; circumferential lines (Paton's lines) 4; nerve fibre layer
      haemorrhage 3; macular stars 5; macular oedema 6; retinal pigment epithelial
      changes 4; subretinal haemorrhage leading to a macular scar 1. Significant visual
      loss attributable to the macular changes was found in 5 eyes in the short term
      and 3 in the long term. The 2 eyes that improved had macular stars. Of the 3 eyes
      that did not improve, 2 eyes had retinal pigment epithelial changes and 1 a large
      subretinal haemorrhage that led to a macular scar. These 3 cases had long
      standing BIH. CONCLUSIONS: The majority of macular changes resolve and do not add
      to visual loss from optic nerve damage. Patients with marked macular oedema are
      at most risk of permanent visual loss and should be considered for early
      treatment such as optic nerve sheath fenestration.

PMID- 10070515
TI  - Carbon monoxide poisoning causes optic neuropathy.
AB  - PURPOSE: To describe the electrophysiological and psychophysical effects of
      carbon monoxide (CO) poisoning on visual function. METHODS: Three patients are
      presented who suffered CO poisoning, two due to suicide attempts and one in the
      course of a road traffic accident. After a full ocular examination, Goldmann
      visual fields, flash and pattern visual evoked potentials (VEPs) and flash and
      pattern electroretinograms (ERGs) were tested. RESULTS: Electrophysiology showed
      reduced or absent N95 components of the pattern ERG and delayed, reduced VEPs. A
      positive-negative-positive (PNP) VEP waveform was seen in two cases. In one case,
      where presentation occurred at an early stage, visual and electrophysiological
      function was improved with hydroxycobalamine. CONCLUSIONS: The combination of ERG
      and VEP findings suggest that CO poisoning can cause a toxic optic neuropathy
      that may have a similar aetiological mechanism to that in tobacco amblyopia.
      Early treatment with hydroxycobalamine may be of some benefit.

PMID- 10070516
TI  - Acute intraoperative suprachoroidal haemorrhage in ocular surgery.
AB  - PURPOSE/BACKGROUND: Acute intraoperative suprachoroidal haemorrhage (AISH) is the
      most sight-threatening complication of ocular surgery. We investigated the visual
      outcomes following this intraoperative event, patient characteristics that may
      predispose to it and the clinical features that may be of prognostic
      significance. METHODS: The records of 45 cases of AISH collected from ophthalmic
      centres in the United Kingdom, Republic of Ireland and Switzerland were reviewed.
      Two satisfactory controls in terms of operative procedure, surgeon, age (+/- 5
      years) and gender were found for each of 33 of our cases. Systemic and ocular
      characteristics were compared for cases and controls, and the visual results of
      all cases of AISH are analysed. RESULTS: Cases and controls differed only in
      terms of axial length and pre-operative intraocular pressure, both of which were
      significantly greater for eyes that experienced an AISH (p < 0.05). Ten eyes
      (22.2%) achieved a final Snellen acuity of 6/12 or better. Statistically
      significant associations with a final acuity of counting fingers or worse
      included spontaneous nuclear expression (p = 0.02), retinal detachment (p <
      0.0001), four-quadrant suprachoroidal haemorrhage (p = 0.007) and vision of
      perception of light or worse at the first dressing (p = 0.0001). Four of the 6
      eyes that experienced an AISH during phacoemulsification surgery had a visual
      outcome of 6/12 or better, and this was significantly greater than for cases
      involving extracapsular cataract surgery (p = 0.004). CONCLUSION: The results
      indicate that longer axial length and higher pre-operative intraocular pressure
      are associated with increased risk of AISH. Poor visual results are more likely
      following spontaneous nuclear expression, retinal detachment, four-quadrant
      suprachoroidal haemorrhage or vision of perception of light or worse at the first
      dressing. The results also suggest that AISH complicating a phacoemulsification
      procedure has a more favourable visual prognosis than AISH that occurs during
      extracapsular cataract surgery.

PMID- 10070517
TI  - Is anterior chamber lens implantation after intracapsular cataract extraction
      safe in rural black patients in Africa? A pilot study in KwaZulu-Natal, South
      Africa.
AB  - PURPOSE: There are an estimated 16 million people blind from cataract world-wide.
      In many areas the routine operation is intracapsular cataract extraction (ICCE).
      The role of modern anterior chamber (AC) intraocular lenses (IOLs) is being
      explored, and they have been shown to be safe and successful in Asia. Are they
      equally safe in rural black African populations? METHODS: One hundred black
      patients aged 50 years and over who attended Edendale Hospital were enrolled in a
      pilot study of insertion of AC IOLs after ICCE. They were followed up for 6
      months. RESULTS: With financial remuneration, the follow-up rate at 8 weeks
      increased from the usual 30% to 72%. At 6 months, 67% of eyes achieved a
      correlated visual acuity of 6/18 or better. Thirty per cent had persistent
      uveitis, 16% had peripheral anterior synechiae beyond the points of haptic
      contact, and 5% had an intraocular pressure greater than 21 mmHg. CONCLUSIONS: A
      randomised trial comparing ICCE with AC IOL and extracapsular cataract extraction
      with posterior chamber IOL is probably not justified at this time in this
      population. However, there may be wide variations in the reaction of the eyes of
      different African ethnic groups to IOLs. In view of the successful use of AC IOLs
      in Asian eyes, further pilot studies of AC IOLs may be warranted in other parts
      of Africa where ICCE is the routine procedure.

PMID- 10070518
TI  - Comparison of the results of primary and secondary implantation of flexible open
      loop anterior chamber intraocular lens.
AB  - PURPOSE: To assess and compare the results of primary and secondary implantation
      of flexible open-loop anterior chamber intraocular lenses (AC-IOLs). METHODS: A
      series of 57 eyes of 56 patients with flexible AC-IOLs were reviewed in two
      groups. In group I (n = 35) an AC-IOL was implanted primarily, because of
      posterior capsule problems during extracapsular cataract extraction (ECCE), and
      in group II (n = 22) secondarily after intracapsular cataract extraction (ICCE).
      Follow-up was from 12 to 38 months. RESULTS: Mean post-operative best-corrected
      visual acuity in group I was significantly lower (20/37.38) than that of group II
      (20/29.20) (p = 0.044). Best corrected visual acuity of 20/40 or better was
      achieved in 19 of 29 eyes (65%) in group I, and in 16 of 21 eyes (76%) in group
      II. The difference was not statistically significant (p > 0.05). In group II 18
      eyes (86%) maintained or improved visual acuity. In group I, 17 eyes (49%) had a
      total of 22 complications, while 7 eyes (32%) had 9 complications in group II (p
      > 0.05). CONCLUSIONS: Flexible open-loop AC-IOLs are suitable for both primary
      and secondary implantation to correct aphakia. Secondary implantation of flexible
      open-loop AC-IOLs after ICCE seems to have a more favourable visual outcome and a
      lower complication rate than primary implantation in complicated ECCE cases.

PMID- 10070519
TI  - A comparison of the effect of hyaluronic acid versus gentamicin on corneal
      epithelial healing.
AB  - PURPOSE: An animal model study was conducted to compare the efficacy of recurrent
      topical applications of hyaluronic acid and gentamicin ointment for the treatment
      of noninfected, mechanical corneal erosions. METHODS: An artificial, controlled
      wound of identical size and depth was inflicted to the corneas of three groups of
      rabbit eyes in order to measure their healing rates. One group was treated with
      hyaluronic acid (10 eyes) while the second group received gentamicin ointment (10
      eyes). The third group remained untreated and served as the control (10 eyes).
      The rate of re-epithelisation was measured at 8-h intervals until complete re
      epithelisation was observed. After complete wound closure, the rabbits were
      killed, and comparative histological examinations were performed. RESULTS: Rabbit
      eyes treated with hyaluronic acid showed a significantly enhanced rate of
      epithelial defect closure compared with untreated eyes and a similar rate to that
      achieved with gentamicin ointment. In the eyes treated with hyaluronic acid a
      normal, multilayered epithelium was observed 48 h after complete healing, whereas
      the gentamicin-treated eyes showed an imperfectly layered epithelium, with
      irregularity of the cuboidal cells. CONCLUSION: While both hyaluronic acid and
      gentamicin enhance corneal epithelial healing at comparable rates, our study
      suggests that hyaluronic acid may have a more favourable effect on the structure
      of the healing epithelium, and can offer an alternative mode of therapy for non
      infectious corneal erosions.

PMID- 10070520
TI  - Endothelial viability of organ-cultured corneas following penetrating
      keratoplasty.
AB  - PURPOSE: To assess endothelial integrity following corneal transplantation using
      human corneas stored in organ culture in the Manchester Eye Bank. METHODS: A
      prospective study was undertaken on 24 patients who had received full-thickness
      corneal grafts using corneas stored in organ culture. The donor corneal
      endothelium was photographed prior to transplantation using light microscopy.
      Specular microscopy and ultrasonic pachometry were performed at 30 days (+/- 3
      days), 12 weeks (+/- 1 week), 26 weeks (+/- 2 weeks) and 52 weeks (+/- 4 weeks)
      following corneal transplantation. The following cell parameters were measured:
      density, area, coefficient of variation (CV) for area, perimeter, diameter, form
      factor and corneal thickness. RESULTS: One year after corneal transplantation
      there was a statistically significant decrease in endothelial cell density (
      39.4%), and a statistically significant increase in endothelial cell area
      (+94.4%), perimeter (+36.1%), diameter (+57.1%) and form factor (+5.8%). However,
      no significant changes were seen in CV or corneal thickness with respect to time
      after transplantation. (There were no significant changes in endothelial cell
      parameters and corneal thickness for 12 control subjects.) CONCLUSIONS:
      Endothelial cell loss occurs at an accelerated rate from corneal transplants.
      This highlights the need for improving corneal endothelial viability during and
      after storage in order to improve the chances of longer-term survival of the
      transplanted cornea.

PMID- 10070521
TI  - Comparison of the efficacy and safety of two eye gels in the treatment of dry
      eyes: Lacrinorm and Viscotears.
AB  - PURPOSE: To compare the efficacy and safety of two carbomer 940 eye gels in the
      treatment of dry eyes: Lacrinorm (also called GelTears), a recently introduced
      eye gel, and Viscotears (also called Vidisic or Lacrigel), used as a reference
      gel. The main difference between the two gels is in the preservative,
      respectively benzalkonium chloride and cetrimide. METHODS: A double-masked,
      randomised, parallel-group study was conducted in 16 centres in four European
      countries. A total of 179 patients suffering from aqueous-deficient dry eye were
      enrolled, of whom 92 were randomised to treatment with Lacrinorm and 87 to the
      reference gel. Gel was instilled four times a day for a period of 30 days.
      RESULTS: After 30 days of treatment, subjective symptoms (the combined scores of
      foreign body sensation, ocular dryness, burning or pain, and photophobia) had
      improved by 50% in the Lacrinorm group and by 45% in the reference gel group, and
      objective test results (break-up time, fluorescein test, Schirmer test, Lissamine
      Green test) by 35-36% in the Lacrinorm group and 25-45% in the reference group.
      The improvements were significant in both treatment groups (p < 0.001), with no
      significant differences between the treatment groups. Subjective local
      tolerability upon instillation on day 30 was rated 'good' or 'very good' by 91%
      of patients in both treatment groups. Adverse events were reported for 21
      patients in the Lacrinorm group and 17 in the reference group, the most frequent
      being discomfort, blurred vision, hyperaemia, burning and itching. The frequency
      and descriptions of adverse events did not differ significantly between the two
      treatment groups. No serious adverse events were reported. CONCLUSIONS: Over the
      period of study, Lacrinorm eye gel was as effective and safe as
      Viscotears/Lacrigel in the treatment of dry eye.

PMID- 10070522
TI  - Comparison of short- and long-term effects of betaxolol and timolol on human
      retinal circulation.
AB  - PURPOSE: To determine the short- and long-term effects of betaxolol and timolol
      on human retinal circulation. METHODS: In a double-masked, randomised, placebo
      controlled study we evaluated the effects of both a one-drop application and a
      twice-daily 2-week application of either topical 0.5% betaxolol hydrochloride or
      topical 0.5% timolol maleate on the retinal circulation in 12 healthy volunteers.
      Laser Doppler velocimetry was used to detect changes in the retinal venous blood
      flow. RESULTS: In both betaxolol- and timolol-treated eyes, intraocular pressure
      decreased significantly compared with baseline values after both 90 min and 2
      weeks. In betaxolol-treated eyes, retinal blood flow did not change significantly
      after 90 min, but increased significantly (14 +/- 9%; p = 0.02) compared with
      baseline after 2 weeks. In timolol-treated eyes, retinal blood flow decreased
      significantly (18 +/- 5%: p = 0.04) compared with baseline after 90 min, and also
      decreased significantly (14 +/- 6%; p = 0.04) compared with baseline after 2
      weeks. CONCLUSIONS: Retinal blood flow increases as a long-term effect of
      betaxolol and decreases as both a short- and long-term effects of timolol.

PMID- 10070523
TI  - The changing pattern of glaucoma referrals by optometrists.
AB  - PURPOSE: To identify any change in optometric referral patterns for suspect
      glaucoma over a 5 year period. METHOD: A retrospective analysis was carried out
      of referrals for suspect glaucoma to a hospital glaucoma clinic from 1988 and
      1993. RESULTS: There was a significant decrease in the positive referral rate
      with time from 56% in 1988 to 37% in 1993 (p = 0.02). Intraocular pressures
      (IOPs) of all patients prior to referral and at presentation to the glaucoma
      clinic were significantly higher in 1988 (25.1 and 25.6 mmHg respectively) than
      in 1993 (22.4 and 23.0 mmHg respectively, p < 0.0005). However, the presenting
      IOPs of eyes with glaucoma were similar in the cohorts (27.5 vs 26.4 mmHg, p =
      0.33). Prior to referral, optometrists performed visual fields on 28% of patients
      in 1988 and on 48% in 1993 (p 0.01), giving an estimate of the cup/disc ratio in
      15% of patients in 1988 and 41% in 1993 (p = 0.0004). CONCLUSIONS: The increased
      false positive referral rate appears to be associated with the increasing use of
      visual field analysers by optometrists and a willingness to refer at lower IOPs.
      Increased false positive referrals result in increased waiting times for hospital
      assessment.

PMID- 10070524
TI  - Longitudinal follow-up of grating acuity in children affected by cerebral palsy:
      results of a 5 year study.
AB  - PURPOSE: To analyse the natural course of visual acuity in subjects affected by
      cerebral palsy. METHODS: During the past 5 years, 16 children underwent repeated
      grating acuity measurements using the acuity card procedure. At the end of the
      follow-up final grating acuity was compared with linear acuity obtained using
      standard optotypes. RESULTS: A good or moderate improvement in grating acuity was
      shown by 14 subjects. However, the general development of grating acuity showed a
      protracted course and early values did not correlate with final grating acuity (r
      = 0.20). Moreover, most of the children showed subnormal vision when measured
      with standard optotypes. CONCLUSION: Clinicians should remain optimistic about
      the potential for some visual development in children affected by cerebral palsy.
      However, great caution should be exercised in extrapolating information from
      early grating acuity measurements. Regular assessments with the acuity card
      procedure are necessary in order to gain an insight into the natural course of
      visual development in children affected by cerebral palsy.

PMID- 10070525
TI  - Comparison of pattern-onset, -reversal and -offset VEPs in treated amblyopia.
AB  - PURPOSE: There are differences in the properties of visual evoked potentials
      (VEPs) to various forms of pattern stimulation and it is not clear how these
      differences reflect macular and parmacular function in amblyopic and normal eyes.
      We assessed pattern-onset, -reversal and -offset VEPs from amblyopic eyes and
      compared them with the responses from the fellow eyes, and from controls, to
      gauge the relative effectiveness of these stimulus modes. METHODS: The three
      modes of pattern stimulation were presented sequentially in a single recording
      run to enable direct comparisons to be made for identical recording conditions.
      Half-field stimulation was used, as this elicits components over the ipsilateral
      and contralateral occipital scalp relative to the stimulated half-field, which
      reflect stimulation of macular and paramacular areas of the visual field.
      Eighteen amblyopes treated by occlusion and 20 control children were studied.
      RESULTS: Multivariate analysis of variance showed significant differences between
      ambylopic and fellow eyes in amblyopes: pattern-onset components were
      significantly attenuated and ipsilateral reversal components were significantly
      prolonged in amblyopic eyes. When fellow eyes of amblyopes were compared with the
      eyes of controls, the reversal P100 and offset P110 and N165 components showed
      significant differences. CONCLUSIONS: Ipsilateral reversal components and onset
      CII and contralateral P105 were the most affected in amblyopic eyes. The
      subnormal findings for the fellow eyes of amblyopes suggest that occlusion may
      have a long-standing physiological effect on the patched eye, not normally
      clinically apparent.

PMID- 10070526
TI  - The epidemiology of ocular injury in a major US automobile corporation.
AB  - PURPOSE: Although occupational eye injuries account for a large proportion of
      ocular injuries, few industry-specific data have been published. To address this
      problem, we examined the epidemiology of eye injuries in a large automobile
      corporation. METHODS: The study population included all hourly-paid persons
      employed between July 1989 and June 1992 at 33 plants of the UAW-Chrysler
      Corporation. Incident ocular injury data were obtained from an active
      surveillance system. Year-end employee censuses were used to estimate the
      population at risk. RESULTS: A total of 1983 work-related eye injuries occurred
      over the 3 year period, with an incidence rate of 14.9 per 1000 person-years.
      Workers aged 20-29 years had the highest incidence of eye injuries (28.2 per 1000
      person-years). Men had a higher incidence of injury than women across all ages,
      with an age-adjusted incidence of 15.6 per 1000 person-years and age-adjusted
      relative risk of 1.5 (95% confidence interval: 1.4, 1.6). Superficial foreign
      bodies and corneal abrasions made up 86.7% of all injuries while open globe
      injury occurred in only 3 cases. Only 25% of workers had been using some form of
      eye protection at the time of injury. Almost one-third (32.3%) of ocular injuries
      resulted in the inability of workers to resume their normal duties for at least 1
      day. CONCLUSION: Workplace eye injuries in the automotive industry account for
      significant avoidable morbidity and lost productivity.

PMID- 10070527
TI  - Lack of evidence for systemic toxicity following topical chloramphenicol use.
AB  - There has been considerable controversy regarding the safety of topical
      chloramphenicol in ophthalmic practice. The evidence for associated
      haematopoietic toxicity in idiosyncratic and dose-dependent forms was reviewed.
      The 7 cases of idiosyncratic haematopoietic reactions associated with topical
      chloramphenicol reported in the literature are refutable evidence for the
      existence of such a response. In Scotland, despite extensive prescription of
      topical chloramphenicol, the incidence of acquired aplastic anaemia was found to
      be low, as were associated reports of blood dyscrasias throughout the UK. The
      epidemiology of acquired aplastic anaemia failed to make an association with
      topical chloramphenicol use. High-performance liquid chromatography (minimum
      detection limit 1 mg/l) was used to investigate whether serum accumulation of
      chloramphenicol occurred after topical therapy in 40 patients. The mean dose of
      chloramphenicol eye drops used after 1 week of treatment was 8.0 mg, and after 2
      weeks, 15.3 mg. As expected, chloramphenicol failed to accumulate to detectable
      levels. This supported the view that topical chloramphenicol was not a risk
      factor for inducing dose-related bone marrow toxicity. Calls for the abolition of
      treatment with topical chloramphenicol based on current data are not supported.

PMID- 10070528
TI  - The role of ophthalmic triage and the nurse practitioner in an eye-dedicated
      casualty department.
AB  - PURPOSE: To evaluate the appropriateness of triage decisions in a busy ophthalmic
      casualty department and to assess the diagnostic and management skills of eye
      dedicated nurse practitioners. METHODS: Three hundred and one consecutive
      patients attending the Birmingham and Midland Eye Centre (BMEC) accident and
      emergency (A&E) department over a 2 week period were included in this prospective
      study. Patients were categorised in terms of urgency in concordance with strict
      guidelines, and the agreement between the final diagnosis and this system of
      prioritisation was then investigated. To evaluate nurse practitioner (NP) skills,
      all patients seen and managed by a NP were also assessed by the most senior
      doctor in casualty at the time in a masked fashion. Waiting times and a breakdown
      of waiting times were also calculated. RESULTS: Upon establishment of a
      diagnosis, triage category allocation was found to be appropriate in all 301
      cases. Fifty patients (16.67%) were seen by the NP. Of these the supervising
      doctor concurred with the NP diagnosis in all cases and with the proposed
      management in 96% of cases. The mean waiting time (+/- SD) was 83.43 +/- 45.84
      min, with a range of 5-335 min. The delay before being attended to was greater
      for less urgent cases as categorised by the triage system. CONCLUSION: This study
      confirms the high standard of diagnostic and management skills of the ophthalmic
      NP and indicates that the triage system of patient prioritisation is accurate.
      Waiting times in the A&E department remain unacceptable and ways of addressing
      this include improved ophthalmic training of general practitioners, diverting a
      greater proportion of non-acute cases to the primary care clinic and expanding
      the role of the NP.

PMID- 10070529
TI  - Blister beetle periorbital dermatitis and keratoconjunctivitis in Tanzania.
AB  - Two cases of periorbital dermatitis and one case of keratoconjunctivitis
      following contact with blister beetle are presented. In Tanzania and Kenya the
      commonest blister beetle is known as Nairobi Fly and is of the genus Paederus.
      Ocular symptoms are common, usually secondary to transfer by the fingers of the
      toxic chemical involved from elsewhere on the skin. Blister beetle
      keratoconjunctivitis has not previously been described in detail.

PMID- 10070530
TI  - Cellular and plasma fibronectin in the aqueous humour of primary open-angle
      glaucoma, exfoliative glaucoma and cataract patients.
AB  - PURPOSE: To compare the concentrations of cellular fibronectin (cFN), plasma
      fibronectin (pFN), tenascin and calcitonin gene-related peptide (CGRP) in the
      aqueous humour in primary open-angle glaucoma (POAG), exfoliative glaucoma (EXFG)
      or cataract (control group). METHODS: The concentrations were determined by
      enzyme-linked immunoassays in the aqueous humour of patients with EXFG (n = 26),
      POAG (n = 29) or cataract (control group, n = 13). RESULTS: The pFN
      concentrations of the three patient groups differed significantly from each other
      (p = 0.0004 in a non-parametric analysis of variance). In multiple comparisons
      EXFG patients showed significantly higher pFN levels than POAG patients (p <
      0.05) or cataract patients (p < 0.01). the cFN level was also significantly
      higher in EXGF patients than in POAG patients (p < 0.05) or cataract patients (p
      < 0.05). The pFN or cFN concentrations of the POAG group did not differ from
      those of the control group. Neither tenascin nor CGRP was detected in the aqueous
      humour of any of our patients. CONCLUSIONS: The significantly higher aqueous
      humour pFN concentration in exfoliative glaucoma may be a consequence of
      disruption of the blood-aqueous barrier and may further add to an increased
      outflow resistance.

PMID- 10070531
TI  - Conjunctival carcinoma in an immunosuppressed patient.

PMID- 10070532
TI  - Recurrent retinal artery occlusion after the disappearance of lupus
      anticoagulant.

PMID- 10070533
TI  - Bilateral anterior ischaemic optic neuropathy following amiodarone.

PMID- 10070534
TI  - Reversible anterior ischaemic optic neuropathy in accelerated hypertension.

PMID- 10070535
TI  - External ocular myiasis due to Oestrus ovis in a tourist returning from North
      Africa.

PMID- 10070536
TI  - Marked thickening of Bruch's membrane in a 17-year-old patient with angioid
      streaks.

PMID- 10070537
TI  - Post-operative myopic shift due to trapped intracapsular Healon.

PMID- 10070538
TI  - Primary (localised non-familial) conjunctival amyloidosis.

PMID- 10070539
TI  - Primary (localised non-familial) conjunctival amyloidosis.

PMID- 10070540
TI  - Vision research, driving and the elderly.

PMID- 10070541
TI  - The value of a phenol red impregnated thread for differentiating between the
      aqueous and non-aqueous deficient dry eye.
AB  - To determine the clinical viability of a phenol red impregnated cotton thread in
      differentiating between normal, aqueous deficient and non-aqueous deficient dry
      eyes. Subjects were recruited on the basis of subjective symptoms, tear
      stability, rose bengal staining, Schirmer test, conjunctival hyperaemia, patency
      and number of meibomian glands, presence of mucin strands, appearance of lower
      tear meniscus. Based on the outcome of the tests, subjects were categorised as
      either aqueous deficient dry eyes, non-aqueous dry eyes or normals. Subjects were
      randomised and a thread was applied by inserting into the lower fornix of the
      right eye and leaving the thread in place for 120 sec. All data was collected
      under similar ambient conditions. After gathering all the data, the codes were
      broken. Mean (+/- S.D.) thread wetting values were, all dry eyes (n = 59) 18.4 mm
      (5.9). Aqueous deficient dry eyes (n = 35), 15.5 mm (4.6). Non-aqueous deficient
      dry eyes [n = 24], 22.7 mm (5.0). For the normals (n = 38), 19.4 mm (5.0).
      Differences between (i) normals and aqueous deficient dry eyes and (ii) aqueous
      deficient and non-aqueous deficient dry eyes were significant (p = 0.01).
      Difference between all dry eyes and normals was not significant. For the aqueous
      deficient and non-aqueous deficient dry eyes only, using a cut-off value of 20 mm
      the calculated sensitivity and specificity values were 86% and 83% respectively.
      This cotton thread test can effectively differentiate between aqueous deficient
      and non-aqueous deficient dry eye.

PMID- 10070542
TI  - Effect of parental myopia on the development of myopia in Hong Kong Chinese.
AB  - A representative sample of Hong Kong Chinese children was followed from 7 to 12
      years of age. Refractive error was measured every year (n = 123 at age 7 years
      and n = 83 at age 12 years), the axial length of the eye was measured at age 12
      years (n = 81) and the refractive status of the parents was also determined.
      Thirty-one percent of the parents in the sample were myopic and at the age of 12
      years 53% of the children were myopic. There was no association between the
      refractive status of the parents and whether or not a child had myopia. The
      probability of a 12-year-old child with early-onset myopia having at least one
      myopic parent was 0.55 and the probability of myopic parents having a myopic
      child was 0.6. There was no difference in the refractive error or the axial
      length of 12-year-old children according to whether neither, one or both parents
      were myopic. The genetic influence on myopia may be different in Caucasian and
      Chinese children, although it is also possible that non-expression of the
      genotype in the parents may have confounded the determination of the inheritance
      pattern of myopia in Hong Kong Chinese children.

PMID- 10070543
TI  - Evaluation of the pinhole pupillometer.
AB  - Evaluation of pupil diameter is used in many clinical and research fields to aid
      diagnosis of neurological disorders and to monitor pharmacological effects upon
      the eye. Methods used to determine pupillary diameter have evolved from simple
      scale measurements to much more complex systems, supposedly improving accuracy
      and repeatability. However, many techniques are restricted to the consulting room
      or research laboratory due to the size of the equipment, its cost, or the
      expertise required. We have evaluated a portable pupillometer originally
      developed by Broca, capable of precise measurements on fixed, dilated pupils,
      that has the potential to be used by unsupervised patients. Luminance levels will
      still need to be controlled because, although luminance does not influence the
      mechanics of the pupillometer itself, it significantly affects the natural pupil.
      The pinhole size should ideally be 1.1 mm in diameter, since smaller pinholes
      underestimate and larger holes overestimate pupil size. The pupillometer also
      exhibited reasonable accuracy in fixed pupils dilated with tropicamide. Pupil
      measurements were overestimated by 0.5% using the 1.1 mm pinholes (insignificant
      if the pupil can be measured to the nearest 0.25 mm) and both intra- and inter
      visit repeatabilities were relatively good. The results from this study therefore
      indicate that the pinhole pupillometer may be of use in pupil research, since it
      facilitates more frequent pupillary measurements over much longer time intervals
      than are currently achievable.

PMID- 10070544
TI  - Sequential pattern-onset, -reversal and -offset VEPs: comparison of effects of
      checksize.
AB  - The effects of checksize on individual components of half-field pattern-onset, 
      reversal and -offset VEPs were studied by presenting these three modes of
      stimulation sequentially in a single recording epoch so as to provide near
      identical recording and subject conditions. Components on the side of the scalp
      ipsilateral and contralateral to the stimulated half-field were measured so as to
      separate the macular and paramacular contributions. Ten checksizes were used (6'
      110'). MANOVA showed a significant effect of checksize: small checksizes enhanced
      onset ipsilateral CII and contralateral P105, as well as all ipsilateral reversal
      components and offset N85 component, suggesting they are reflecting macular
      function. Onset CI, and contralateral reversal N105 and offset N115 components
      increased in amplitude with increasing checksize, suggesting they are
      predominantly of paramacular origin. The morphology of the contralateral onset
      P105 component was checksize dependent: small checks (< 35') produced a sharply
      defined positivity (macular sub-component), whereas larger checks produced a
      broadened/bifid waveform, suggesting the emergence of a later paramacular sub
      component.

PMID- 10070545
TI  - The effect of spherical and other aberrations upon the modulation transfer of the
      defocussed human eye.
AB  - Relative modulation transfer is defined as contrast sensitivity under blur
      normalised to contrast sensitivity at optimum focus. Measured relative modulation
      transfer exceeds relative modulation transfer as calculated for aberration free
      optics at higher spatial frequencies (> 2 cpd). The contribution of spherical
      aberration to this discrepancy was studied. In the case of positive blur,
      spherical aberration increases relative modulation transfer for spatial
      frequencies of approximately 4 cpd and over. However, spherical aberration does
      not explain the entire difference between measured and calculated relative
      modulation transfer. Chromatic aberration does not provide a noticeable
      additional explanation. With negative blur, spherical aberration increases the
      relative modulation transfer much more. The effect of other monochromatic
      aberrations on relative modulation transfer is discussed.

PMID- 10070546
TI  - A generalization of Prentice's law for lenses with arbitrary refracting surfaces.
AB  - A generalization of the Prentice's law is presented in this paper. The idea
      consists of removing some (but not all) of the approximations that comprise the
      paraxial approach. In that way, we obtain a new formulation that permits us to
      compute the prismatic power of a lens made up of arbitrary refracting surfaces,
      and to improve the precision obtained by Prentice's law when applied to monofocal
      lenses. The resulting formalism is simple and manageable and its derivation leads
      us to a precise definition of the local dioptric power matrix, introduced in a
      previous paper, as well as a better understanding of the same.

PMID- 10070547
TI  - Could a cycloplegic agent be replaced by a fogging or a corrective lens in the
      biometric measurement of the crystalline lens?
AB  - This study investigated whether a fogging or a corrective lens could be used to
      replace a cycloplegic agent in the ultrasonic measurement of crystalline lens
      thickness in myopia. A group of 28 Hong Kong Chinese adults with myopia was
      recruited. The crystalline lens thickness of the examined eye was measured by A
      scan ultrasonography while the fixating eye was in one of three conditions: fog
      (+2.00 D fogging lens), full corrective lens, or cycloplegia (50 minutes after
      instillation of 1% cyclopentolate HCl). We found that the mean lens thickness was
      significantly different between the three conditions in our myopic subjects. The
      mean crystalline lens thickness under fogging and corrective lens conditions was
      significantly greater than the cycloplegic condition by 0.09 mm and 0.11 mm,
      respectively. The 95% limits of agreement compared to cycloplegia (fogging: -0.32
      to +0.14; corrective: -0.35 to +0.13) showed marked intersubject variability,
      indicating that there is a risk of overestimating the lens thickness when
      substituting cycloplegia with either a fogging or a corrective lens.

PMID- 10070548
TI  - A study of the accuracy of corneal reflection pupillometers.
AB  - We studied the accuracy of nine corneal reflection pupillometers made by three
      manufacturers, because, at the time of investigation, we could not find any
      information about their accuracy. For this purpose two steel balls separated by
      spacer bars, were positioned to simulate nominal inter-pupillary distance (PD)
      measurements of 55, 60, 65 and 70 mm. Ten measurements of each 'PD' for distance
      vision, were made by two experienced observers, with each instrument. We found
      that interobserver differences in measurement were clinically insignificant most
      of the time, although some data sets were significantly different statistically.
      The most consistent and accurate measurements of PD were achieved with PD 65 mm.
      The average error in mean value of the measurements for all PD's, was 2.3 mm, and
      the average of the standard deviation in our measurements, was 0.26 mm.
      Significant sources of error were poor eye relief in all instruments evaluated,
      as well as friction in the scale adjustment mechanism in some instruments. Our
      findings show that while a given pupillometer may be relied upon to give
      consistent readings (within the limits of clinically acceptable error), its
      accuracy should be checked periodically, especially for very small and very large
      PD measurements.

PMID- 10070549
TI  - Reliability of the non-contact corneal aesthesiometer and its comparison with the
      Cochet-Bonnet aesthesiometer.
AB  - AIMS: To determine the repeatability of measurement of the corneal sensation
      threshold using the Non-Contact Corneal Aesthesiometer (NCCA); to evaluate the
      effect of the air-jet diameter and stimulus duration on the threshold; and to
      compare the sensation thresholds found with the NCCA and with the Cochet-Bonnet
      Aesthesiometer (C-BA), on the same group of normal, human subjects. METHODS: For
      all experiments, only the central corneal sensation thresholds were measured. (1)
      NCCA Repeatability; 17 subjects tested at the same time on five separate days.
      (2) NCCA Air-Jet Diameter; 15 subjects tested using four different air-jets:
      0.35, 0.5, 1 and 2 mm. (3) NCCA Stimulus Duration; 15 subjects tested using three
      stimulus durations: 0.5, 0.9 and 1.5 sec. (4) NCCA and C-BA; 43 subjects tested
      using each instrument in turn. RESULTS: (1) No significant differences in mean
      sensation threshold were detected across the five days of testing, or between
      individual days. (2) 0.5 and 1 mm air-jets produce least variability in mean
      sensation threshold. (3) No significant difference in mean sensation thresholds
      was found between the three test durations. (4) For each subject, there was no
      correlation between each instrument's mean sensation threshold. CONCLUSIONS: (1)
      The NCCA was able to assess the corneal sensation threshold in an accurate and
      repeatable manner. (2) The optimum test parameters were found using the 0.5 mm
      air-jet, over a stimulus duration of 0.9 sec. (3) The C-BA has serious
      deficiencies in its design which limit its ability to accurately measure corneal
      sensitivity at low stimulus thresholds.

PMID- 10070550
TI  - Daylight simulators and colour vision tests.
AB  - Our previous studies have shown that the influence of the illuminating source
      used for colour vision examination on the intended function of the test is very
      test dependent, some being relatively unaffected by source characteristics while
      others can be significantly affected. The effects can even differ between the
      plates of one pseudo-isochromatic plate test set. In addition, in previous
      studies we have considered a large range of sources on one test at a time. For
      this study the emphasis is on four fluorescent tube sources, all of which meet
      the requirements of the CIE method for assessing the quality of daylight
      simulators. The colour vision tests include sorting tests (the D-15 tests
      [Standard, Lanthony Desat and Adams Desat]), the Lanthony New Colour Test and the
      FM100 Hue Test, pseudo-isochromatic plate tests (Ishihara, Standard Pseudo
      isochromatic Plates Volume 1, Hahn New Colour Test and Lanthony Tritan Album) and
      a matching test (TCU Test). Two examples are quoted here. The tests were assessed
      on the basis of alignment of the colours of the tests to protanopic and
      deuteranopic confusion axes and, where appropriate, to the tritanopic confusion
      axis. The data and analysis indicate that the four fluorescent tubes are
      essentially equivalent.

PMID- 10070552
TI  - Mystery spots.

PMID- 10070551
TI  - Glaucoma detection rate: a useful concept, to be distinguished from accuracy of
      referral (positive predictive value)

PMID- 10070553
TI  - Measurement and modelling of perceived slant in surfaces represented by freely
      viewed line drawings.
AB  - Simple pictures under everyday viewing conditions evoke impressions of surfaces
      oriented in depth. These impressions have been studied by measuring the slants of
      perceived surfaces, with probes (rotating arrowheads) designed to respect the
      distinctive character of depicted scenes. Converging arguments indicated that the
      perceived orientation of the probes was near theoretical values. A series of
      experiments showed that subjects formed well-defined impressions of depicted
      surface orientation. The literature suggests that perceived objects might be
      'flattened', but that was not the general rule. Instead, both mean slant and
      uncertainty fitted models in which slant estimates are derived in a relatively
      straightforward way from local relations in the picture. Simplifying pictures
      tended to make orientation estimates less certain, particularly away from the
      natural anchor points (vertical and horizontal). The shape of the object affected
      all aspects of the observed-object/percept relationship. Individual differences
      were large, and suggest that different individuals used different relationships
      as a basis for their estimates. Overall, data suggest that everyday picture
      perception is strongly selective and weakly integrative. In particular, depicted
      slant is estimated by finding a picture feature which will be strongly related to
      it if the object contains a particular regularity, not by additive integration of
      evidence from multiple directly and indirectly relevant sources.

PMID- 10070554
TI  - Role of spatial and temporal coincidence in depth organization.
AB  - The linking of spatial information is essential for coherent space perception. A
      study is reported of the contribution of temporal and spatial alignment for the
      linkage of spatial elements in terms of depth perception. Stereo half-images were
      generated on the left and right halves of a large-screen video monitor and viewed
      through a mirror stereoscope. The half-images portrayed a black vertically
      oriented bar with two brackets immediately flanking this bar and placed in
      crossed or uncrossed disparity relative to the bar. A pair of thin white
      'bridging lines' could appear on the black bar, always at zero disparity.
      Brackets and bridging lines could be flickered either in phase or out of phase.
      Observers judged whether the brackets appeared in front of or behind the black
      bar, with disparity varied. Compared to conditions when the bridging lines were
      absent, depth judgments were markedly biased toward "in front" when bridging
      lines and brackets flashed in temporal phase; this bias was much reduced when the
      bridging lines and brackets flashed out of phase. This biasing effect also
      depended on spatial offset of lines and brackets. However, perception was
      uninfluenced by the lateral separation between object and brackets.

PMID- 10070555
TI  - Change in visually perceived eye level without change in perceived pitch.
AB  - Both the physical elevation that appears to correspond to eye level and the
      visually perceived pitch of a visual field are linear functions of the physical
      pitch of a normally illuminated, complexly structured visual field. One of the
      possible bases for the large effect of physical pitch on the elevation of
      visually perceived eye level (VPEL) is that the visual field generates a mental
      representation which specifies spatial coordinates and these determine the VPEL
      elevation ('implicit-surface model'; ISM). The influence on the elevation of VPEL
      is nearly as large when the visual field contains either one or two long pitched
      from-vertical or rolled-from-vertical lines in otherwise total darkness as when
      it consists of a well-illuminated and complexly structured pitched room (L Matin
      and W Li, 1994 Vision Research 34 311-330), and, in order to examine the ISM, we
      employed a rolled-from-vertical, two-line configuration within a frontoparallel
      plane viewed in otherwise total darkness. Measurements of visually perceived
      pitch were made by a manual matching procedure and VPEL measurements were made by
      the psychophysical setting of the elevation of a small visual target to appear at
      eye level while each of three subjects viewed the two-line configuration at each
      of three horizontal eccentricities with the configuration at each of seven roll
      orientations. In direct contradiction to the ISM, the perceived pitch of the two
      line configuration did not deviate significantly from the erect orientation
      ('vertical') for any roll at any eccentricity, but the elevation of VPEL changed
      systematically with the roll of the configuration both at left and at right
      eccentricities, and did not change at all with the two-line configuration
      centered on the median plane. Consistent with our previous work and with our
      previous interpretation regarding the basis for VPEL (L Matin and W Li, 1994
      Vision Research 34 2577-2598), the variation of VPEL for the two-line visual
      field equals the average of the VPEL variations produced by viewing each of the
      single lines separately.

PMID- 10070556
TI  - Anisotropy in haptic curvature and shape perception.
AB  - An investigation was undertaken into whether haptic comparison of curvature and
      of shape is influenced by the length/width ratio of the hand. For this purpose
      three experiments were conducted to test the curvature matching of curved strips
      (experiment 1), the curvature matching of cylindrically curved hand-sized
      surfaces (experiment 2), and the shape discrimination of elliptically curved hand
      sized surfaces (experiment 3). The orientation of the stimuli with respect to the
      fingers was varied. The results of the two matching experiments showed that a
      given curvature is judged to be more curved when touched along the fingers than
      when touched across the fingers. The phenomenal flatness along and across the
      fingers was found to be different and subject dependent. The results of the shape
      discrimination experiment showed that the orientation of ellipsoidal surfaces
      influences the judgments of the shapes of these surfaces. This influence could be
      predicted on the basis of results of the second matching experiment. It is
      concluded that similar mechanisms underlie the (anisotropic) perception of
      curvature and shape. For the major part the trends in the results can be
      explained by the length/width ratio of the hand and the phenomenal flatnesses.

PMID- 10070557
TI  - A moving cast shadow diminishes the Pulfrich phenomenon.
AB  - It is demonstrated that the presence of a moving cast shadow diminishes the
      Pulfrich phenomenon. This complements previous work by Kersten, Knill, Mamassian,
      and Bulthoff [1996 Nature (London) 379 31] indicating that visible cast shadows
      can override monocularly based cues to the perceived trajectory of a moving
      object. The present finding with the Pulfrich phenomenon indicates the
      effectiveness of shadows for overriding binocularly based cues to the perceived
      trajectory of a moving object.

PMID- 10070558
TI  - Test of a convergence model for color transparency perception.
AB  - Models of color transparency suggest that a region in which colors of surfaces
      converge in color space will appear transparent. The convergence is described by
      a transparency parameter alpha and a target of convergence. To test such models
      psychophysically, observers were presented a display with four colored areas. The
      colors of three of the areas were chosen in advance by the experimenter. The task
      of the observer was to choose the color of the fourth area to make a central
      region appear transparent. Settings for the fourth color were collected for a
      total of twenty-four color combinations chosen from three planes in color space.
      Observers' settings agreed well with the model, which predicts that choices for
      the fourth color lie along a line segment in color space that is parameterized by
      alpha. The results suggest further that color discriminability and color
      opponency also influence transparency judgment.

PMID- 10070559
TI  - Influence of individual differences in temporal sensitivity on timing
      performance.
AB  - This research was designed to examine the consistency of individual differences
      in timing. Subjects were tested initially on a temporal-signal-detection task. In
      a series of trials, subjects judged whether a stimulus figure was displayed for
      either 12 s or greater than 12 s. Task performance was used to classify the
      subjects into groups with high or low temporal sensitivity (d'). Later, the
      subjects were tested on two classic time-judgment tasks. In a temporal
      interference task, subjects reproduced intervals of 8-16 s during which they had
      rehearsed 0, 3, or 7 digits. Absolute error in time judgments increased linearly
      as a function of task demands. However, subjects with low temporal sensitivity
      made more error under all conditions compared with those with high sensitivity.
      In an isochronous-tapping task, subjects produced a series of 2-s and 5-s
      intervals. The low-temporal-sensitivity group produced more variable and
      inaccurate responses than the high-sensitivity group. The results demonstrate
      cross-situational consistency in timing performance across different tasks, time
      judgment methods, and stimulus durations.

PMID- 10070560
TI  - A new stereoscopic illusion: eyes popping out and sinking in.
AB  - A stereoscopic illusion is produced by manipulating the binocular disparity of
      the irises in stereo pairs of human faces. These stimuli elicit unnatural
      percepts of the irises popping out of the face or sinking in inside the head.

PMID- 10070561
TI  - Interrelationship between pharmacokinetics and pharmacodynamics in choosing the
      appropriate antibiotic and the dosage regimen for treating acute exacerbations of
      chronic bronchitis.

PMID- 10070562
TI  - Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and
      diagnosis.
AB  - Idiopathic pulmonary haemosiderosis (IPH) is a rare clinical entity characterized
      by recurrent episodes of diffuse alveolar haemorrhage, often presenting with
      haemoptysis. Many patients have iron deficiency anaemia due to deposition of
      haemosiderin iron in the alveoli, and eventually develop moderate pulmonary
      fibrosis. Typically, intensive search for an aetiology ends up negative. There is
      no evidence of pulmonary vasculitis or capillaritis. The aetiology is obscure,
      but may be an immunological or toxic mechanism causing a defect in the basement
      membrane of the pulmonary capillary. IPH affects both children and adults. During
      an acute episode, a chest X-ray demonstrates bilateral, alveolar infiltrates.
      Sputum examination discloses haemosiderin-laden alveolar macrophages. Diagnosis
      is established by lung biopsy (fiber-optic or thoracoscopic), showing large
      numbers of haemosiderin-laden macrophages in the alveoli and without evidence of
      capillaritis or deposition of immunoglobulins. Corticosteroids and/or
      immunosuppressive drugs may be effective during an acute bleeding episode, and
      may in some patients improve symptoms and prognosis on the long-term, but the
      response to treatment displays great interindividual variation.

PMID- 10070563
TI  - Exhaled nitric oxide; relationship to clinicophysiological markers of asthma
      severity.
AB  - Bronchial asthma is an airway disorder associated with bronchial
      hyperresponsiveness, variable airflow obstruction and elevated levels of nitric
      oxide (NO) in exhaled air. The variables all reflect, in part, the underlying
      airway inflammation in this disease. To understand their interrelationships we
      have investigated the relationship between exhaled NO levels and
      clinicophysiological markers of asthma severity. Twenty-six steroid naive atopic
      asthmatics participated in the analysis. All were given diary cards and were
      asked to record their peak expiratory flow (PEF) rates twice daily together with
      their asthma symptom scores and beta-agonist use. Diary cards were collected 2
      weeks later and measurements of exhaled NO levels, FEV1 and histamine bronchial
      hyperreactivity (PC20 histamine) were undertaken. Exhaled NO levels were
      significantly higher in our study population than in normal control subjects and
      correlated negatively with PC20 histamine (r = -0.51; P = 0.008) and positively
      with PEF diurnal variability (r = 0.58; P = 0.002), but not with symptom scores,
      beta-agonist use of FEV1 (%). We conclude that a significant relationship exists
      between exhaled NO levels and the two characteristic features and markers of
      asthma severity, namely bronchial hyperreactivity and PEF diurnal variability.
      The lack of correlation between symptom score and beta-agonist use, of FEV1 (%)
      predicted and exhaled NO suggests that these measures are reflective of differing
      aspects of asthma.

PMID- 10070564
TI  - Spirometric reference equations for older adults.
AB  - The objective of this study was to develop spirometric reference equations for
      healthy, never-smoking, older adults. It was designed as a cross-sectional
      observational study consisting of 1510 Seventh Day Adventists, ages 43-79 years
      enrolled in a study of health effects of air pollutants. Individuals were
      excluded from the reference group (n = 565) for a history of current respiratory
      illness, smoking, or chronic respiratory disease, and for a number of 'non
      respiratory' conditions which were observed in these data to be related to lower
      values of FEV1. Gender-specific reference equations were developed for the entire
      reference group and for a subset above 65 years of age (n = 312). Controlling for
      height and age, lung function was found to be positively related to the
      difference between armspan and height, and in males was found to be quadratically
      related to age. The predicted values for this population generally fell within
      the range of those of other population groups containing large numbers of adults
      over the age of 65 years. Individuals with lung function below the 5th percentile
      in this sample, however, could not be reliably identified by using the lower
      limits of normal predictions commonly used in North America and Europe.

PMID- 10070565
TI  - Cigarette smoking decreases interleukin-8 secretion by human alveolar
      macrophages.
AB  - Cigarette smoking can impair pulmonary immune function, and hence influences the
      development of lung diseases. Interleukin-8 (IL-8) is a proinflammatory peptide
      and a potent chemotactic factor for neutrophils, and is produced by both immune
      and non-immune cells including monocytes and alveolar macrophages (AM). We
      investigated the effect of cigarette smoking on the secretion of IL-8 by human
      AM. The IL-8 concentration in bronchoalveolar lavage fluid (BALF) was much higher
      in smokers than in non-smokers (18.4 +/- 3.9 vs 4.1 +/- 1.0 pg ml-1; P < 0.005).
      However, spontaneous IL-8 secretion by cultured AM was lower in smokers than in
      non-smokers (46.8 +/- 12.7 vs 124.1 +/- 24.0 ng ml-1; P < 0.01). When stimulated
      with lipopolysaccharide (LPS), AM from smokers secreted significantly less IL-8
      than those from non-smokers at all tested concentrations of LPS. In contrast, the
      amount of IL-8 secreted by peripheral blood monocytes with or without LPS
      stimulation was comparable in smokers and non-smokers. These observations
      indicate that smoking decreases IL-8 secretion by AM, which may modify or
      decrease the inflammatory response in the lung.

PMID- 10070566
TI  - The role of domestic factors and day-care attendance on lung function of primary
      school children.
AB  - The results of studies examining the relationship of domestic factors to lung
      function are contradictory. We therefore examined the independent effects of
      maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS),
      the presence of a cat, type of heating and cooking used in the home and day-care
      attendance on lung function after controlling for socioeconomic status (SES).
      Nine hundred and eighty-nine children from 18 Montreal schools were studied
      between April 1990 and November 1992. Information on the child's health and
      exposure to domestic factors was collected by questionnaire. Spirometry was
      performed at school. The data were analysed by multiple linear regression with
      percent predicted FEV1, FVC, and FEV1/FVC as dependent variables. In the overall
      sample (both sexes combined), cat in the home (regression coefficient, beta = 
      1.15, 95% confidence interval, CI: -2.26-(-)0.05) and electric baseboard units
      (beta = -1.26, 95% CI: -2.39-(-)0.13) were independently associated with a lower
      FEV1/FVC, while day-care attendance (beta = -2.05, 95% CI: -3.71-(-)0.40)
      significantly reduced FEV1. Household ETS was significantly associated with
      increasing level of FVC (beta = 2.86, 95% CI: +0.55 to +5.17). In boys but not
      girls, household ETS (beta = -2.13, 95% CI: -4.07-(-)0.19) and the presence of a
      cat (beta = -2.19, 95% CI: -3.94-(-)0.45) were associated with lower FEV1/FVC. By
      contrast, day-care attendance was associated with lower FEV1 (beta = -2.92, 95%
      CI: -5.27-(-)0.56) and FEV1/FVC (beta = -1.53, 95% CI: -2.73-(-)0.33) in girls
      only. In conclusion, the results provide evidence that domestic factors and day
      care attendance primarily affected airway caliber and gender differences were
      apparent in the effects of these factors.

PMID- 10070567
TI  - Time course of respiratory decompensation in chronic obstructive pulmonary
      disease: a prospective, double-blind study of peak flow changes prior to
      emergency department visits.
AB  - The aim of this study was to look at changes in peak expiratory flow rates (PEFR)
      prior to emergency department visits for decompensated chronic obstructive
      pulmonary disease (COPD). It was designed as a prospective, double-blind study at
      the Albuquerque Veterans Affairs Medical Center. Twelve patients with an
      irreversible component of airflow obstruction on pulmonary function tests were
      assessed. At entry, all subjects were instructed in the use of a mini-Wright peak
      flow meter with electronic data storage. They then entered a 6-month monitoring
      phase in which they recorded PEFR twice daily, before and after bronchodilators.
      The meter displays were disabled so that the patients and their physicians were
      blinded to all values. Medical care was provided in the customary manner.
      Patients were considered to have respiratory decompensation if they required
      treatment for airflow obstruction in the Emergency Department (ED) and no other
      causes of dyspnea could be identified. Simple linear regression was used to model
      changes in PEFR over time. The 12 subjects had 22 episodes of respiratory
      decompensation during 1741 patient-days of observation. Two episodes could not be
      analysed because of missing values. Ten episodes in seven subjects were
      characterized by a significant linear decline in at least one peak flow parameter
      prior to presentation. The mean rates of change for the four daily parameters
      varied from 0.22% to 0.27% predicted per day (or 1.19 to 1.44 1 min-1 day-1). The
      average decrement in these parameters ranged from 30.0 to 33.8 1 min-1 (or 18.6%
      25.9% of their baseline values). No temporal trends were found for the 10
      episodes occurring in the other five subjects. We concluded that respiratory
      decompensation is characterized by a gradual decline in PEFR in about half of
      cases. Future studies should be done to elucidate the mechanisms of respiratory
      distress in the other cases.

PMID- 10070568
TI  - A comparative study of the effects of ketotifen, disodium cromoglycate, and
      beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients
      with atopic asthma.
AB  - Asthma is a chronic inflammatory disorder of the airways that is characterized by
      infiltration of many inflammatory cells into the bronchial mucosa. We compared
      the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone
      dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the
      asthma symptoms of patients with atopic asthma. In this 12-week parallel study,
      32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n
      = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each
      subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and
      after treatment, pulmonary function and bronchial responsiveness to methacholine
      were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and
      after treatment. Biopsy specimens were obtained by bronchoscopy. We performed
      immunohistochemistry using specific monoclonal antibodies for activated
      eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our
      clinical findings showed significant improvement in symptom score and bronchial
      responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups
      had significantly better symptom scores than the ketotifen group (P < 0.05, both
      groups). PEF significantly increased in the DSCG group in comparison to the
      ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in
      the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen
      group. Compared with their baseline values, treatment significantly decreased
      EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01).
      Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant
      decreases in AA1+ mast cell count, but this was not observed in the ketotifen
      group. Comparing before- and after-treatment values, only the DSCG group
      exhibited a significant decrease in the number of CD8+ T cells (P < 0.01).
      Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by
      examination of the bronchial mucosa of asthmatic patients; and both the DSCG and
      BDP groups had better clinical responses than the ketotifen group.

PMID- 10070569
TI  - Effect of hyperoxia on human macrophage cytokine response.
AB  - In the development of lung damage induced by oxidative stress, it has been
      proposed that changes in alveolar macrophages (AM) function with modifications in
      cytokine production may contribute to altered repair processes. To characterize
      the changes in profiles of cytokine production by macrophages exposed to
      oxidants, the effects of hyperoxia (95% O2) on interleukin (IL)-1 beta, IL-6, IL
      8, and tumour necrosis factor-alpha (TNF-alpha) expression were studied.
      Experiments were first performed using AM obtained from control subjects and
      children with interstitial lung disease. Results showed that a 48 h O2 exposure
      was associated with two distinct patterns of response: a decrease in TNF-alpha,
      IL-1 beta and IL-6 expression, and an increase in IL-8. To complete these
      observations we used U937 cells that were exposed for various durations to
      hyperoxia. We confirmed that a 48 h O2 exposure led to similar changes with a
      decrease in TNF-alpha, IL-1 beta and IL-6 production and an increase in IL-8.
      Interestingly, this cytokine response was preceded during the first hours of O2
      treatment by induction of TNF-alpha, IL-1 beta and IL-6. These data indicate that
      hyperoxia induces changes in the expression of macrophages inflammatory
      cytokines, and that these modifications appear to be influenced by the duration
      of O2 exposure.

PMID- 10070570
TI  - Drainage of spontaneous pneumothorax using an intravenous catheter. Immediate and
      long-term results.

PMID- 10070571
TI  - Broncholithiasis: rare but still present.
AB  - Broncholithiasis is a rare but distinct and potentially dangerous pulmonary
      problem that still needs to be considered in the differential diagnosis of some
      patients with bronchial obstruction. Broncholiths originate from calcified
      material in peribronchial lymph nodes eroding into the tracheobronchial tree. The
      clinical and chest X-ray signs are usually non-specific, but the diagnosis can
      nowadays be made based on clinical suspicion, CT-scan and fibre-optic
      bronchoscopy findings, so that a malignant cause of airway obstruction can be
      ruled out. The removal of broncholiths during fibre-optic bronchoscopy is seldom
      possible and rather dangerous. They can be removed safely by rigid bronchoscopy
      with the aid of Nd-YAG laser photocoagulation. Thoracotomy is indicated in
      complicated cases with fistula formation or severe bleeding.

PMID- 10070572
TI  - A case of lymphomatoid granulomatosis mimicking sarcoidosis.

PMID- 10070573
TI  - Salmonella empyema following splenic biopsy.

PMID- 10070574
TI  - Pulmonary infarction revealing pulmonary Takayasu's arteritis.

PMID- 10070575
TI  - Invasive pulmonary aspergillosis in an insulin-dependent diabetic.

PMID- 10070576
TI  - Endobronchial non-Hodgkin's lymphoma.

PMID- 10070577
TI  - Acute respiratory failure due to miliary tuberculosis in a patient with
      idiopathic CD4+ T-lymphocytopaenia.

PMID- 10070578
TI  - Diagnosis of pulmonary veno-occlusive disease: new criteria for biopsy.

PMID- 10070579
TI  - Transient cortical blindness: a complication of bronchial artery embolization.

PMID- 10070580
TI  - Pulmonary vasculitis associated with anti-Jo-1 antibodies.

PMID- 10070581
TI  - Pulse oximetry in smokers.

PMID- 10070582
TI  - Cattle TB crisis? Human implications.

PMID- 10070583
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae in Fukuoka City, Japan, in
      the early 1980s and 1997-1998: emergence of high-level fluoroquinolone
      resistance.

PMID- 10070584
TI  - Vancomycin-resistant Enterococcus faecium strains with highly similar pulsed
      field gel electrophoresis patterns containing similar Tn1546-like elements
      isolated from a hospitalized patient and pigs in Denmark.

PMID- 10070585
TI  - Predictors of failure to return for HIV test result and counseling by test site
      type.
AB  - The objective of this study was to determine the primary predictors of failure to
      return (FTR) for HIV test results and counseling by test site type from among
      those variables collected during the pretest, risk assessment session. The study
      sample consisted of 366,280 clients tested for HIV antibodies over an 18-month
      period at publicly funded testing sites throughout California. The FTR rate for
      the entire sample was 16.4%. The most significant predictor of FTR was the site
      type at which resting took place, with those testing at sexually transmitted
      disease clinics four times, and mobile testing clients over three times, more
      likely to fail to return than alternative test site clients. Independent
      predictors of FTR differed dramatically across the types of testing sites
      examined. Implications of these results for devising site-specific counseling
      strategies to reduce FTR are examined and possible effects on FTR of more rapid
      testing procedures and home testing are considered. Suggestions for future
      research are outlined.

PMID- 10070586
TI  - Psychosocial correlates of voluntary HIV antibody testing in college students.
AB  - Although past research has examined correlates of HIV testing, much of it has
      focused on demographic differences between tested and nontested individuals. The
      present study examined psychosocial differences between individuals seeking a
      voluntary HIV test at a college student health center and individuals who have
      never had an HIV test. Variables included in the model were four components of
      the health belief model (perceived susceptibility, perceived severity, perceived
      benefits, perceived barriers), as well as perceived norms, consideration of
      future consequences, and risky sexual behavior. Results suggest that individuals
      seeking an HIV test perceived more benefits of having a test, tended to perceive
      fewer barriers to having a test, were higher in consideration of Future
      Consequences, and engaged in riskier sexual behavior than individuals never
      having had an HIV test. Implications for both HIV testing interventions and the
      health belief model are discussed.

PMID- 10070587
TI  - Voluntary HIV testing in prison: do women inmates at high risk for HIV accept HIV
      testing?
AB  - This study examined the proportion of women inmates who accepted HIV testing and
      the sociodemographic, criminal, and HIV-related risk characteristics associated
      with accepting such testing in a state prison offering voluntary HIV testing. A
      consecutive sample of 805 women felons admitted to the North Carolina
      Correctional Institution for Women between July 1991 and November 1992 was
      interviewed. Of these inmates, 680 (84%) granted permission to access their
      medical records and had complete information on relevant characteristics. Seventy
      one percent of the women inmates accepted HIV testing. In multivariate analysis,
      the exchange of sex for money or drugs and the conviction for a drug crime were
      significantly associated with accepting HIV testing. Injection drug use, drug
      injecting sex partners, and a history of a sexually transmitted disease were not
      significantly associated with accepting HIV testing. A prison-based voluntary HIV
      testing program appears to be reaching a substantial proportion of women inmates
      potentially at risk for HIV, especially women inmates who exchanged sex for money
      or drugs.

PMID- 10070588
TI  - Correlates of condom use stage of change: implications for intervention.
AB  - A telephone survey was used to collect data on attitudes, beliefs, and practices
      concerning condom use among 812 African Americans with regular sex partners and
      of reproductive age in Baltimore. Condom use was "staged" according to
      Prochaska's model of stage of behavioral change. Characteristics of the
      respondents' sexual relationships, peer characteristics, and demographic and
      psychosocial characteristics were examined for their association with the stage
      of condom use. Multiple logistic regression analysis revealed that a partner's
      reaction to condom use, condom use self-efficacy with the partner, condom use
      outcome expectancy with the partner, perceived partner risk, length of
      relationship, sterility, cohabitation, perceived vulnerability to HIV infection
      and perceived peer norms about condom use were each independently related to
      staged condom use. Gender differences in the relationship of these independent
      variables with stages of change were found. Implications for intervention include
      differential treatment by gender and stage of change. Couples should also be
      considered for intervention.

PMID- 10070589
TI  - Hope and resilience in suicide ideation and behavior of gay and bisexual men
      following notification of HIV infection.
AB  - Upon being notified that they are positive for HIV, people often experience
      terror and confusion. At the beginning stages of coping with HIV diagnosis,
      suicide ideation and behavior may arise as the infected person begins to envision
      frightening images of a future life with AIDS. We examined the narratives of gay
      men who contemplated or attempted suicide soon after they had learned of their
      HIV infection. We found that suicidal ideation and attempt often provoked a
      process of coping with HIV disease, leading to a redefinition of the meaning of
      HIV, enhancing one's sense of control over life, and prompting a renewed effort
      at self-help and help seeking, a new commitment to life, and a reappraisal of
      personal goals. We recommend that clinicians and HIV counselors be cognizant of
      these positive symbolic functions of suicidality in coping with HIV infection.
      Allowing people who were recently diagnosed with HIV to discuss suicidality may
      allow them to move toward acceptance and commitment to life.

PMID- 10070590
TI  - Experiences of 100 men who have sex with men using the Reality condom for anal
      sex.
AB  - A self-administered, anonymous questionnaire examining opinions and experiences
      of using Reality, the "female" condom, for anal sex was completed by a
      convenience sample of 100 men who have sex with men (MSM). Eighty-six percent of
      respondents said they would use Reality again; 54% would rather use Reality than
      penile condoms. Acceptability was higher among MSM who were HIV positive, in
      nonmonogamous relationships, or who had serodiscordant partners. Negative
      experiences included: difficulty inserting (33%), irritation (17%), bunching up
      (12%), unpleasant texture (10%), and noise (9%). Breakage was reported three
      times in 334 episodes of use. Although no available data compare preferences and
      efficacy of Reality to penile condoms, Reality is a welcome alternative for some
      MSM who have difficulty consistently using penile condoms and probably reduces
      HIV transmission compared with unprotected anal sex. Research to more
      definitively assess Reality as a risk reduction method for MSM is greatly needed.

PMID- 10070591
TI  - Factors influencing attitudes within AIDS service organizations toward the use of
      research-based HIV prevention interventions.
AB  - Although the efficacy of small-group, risk reduction interventions based on
      cognitive behavioral principles has been widely documented in HIV behavioral
      research literature, little is known about how AIDS service organizations (ASOs)
      view these research-based models. From a nationwide sample of 77 ASOs, this study
      assessed factors influencing attitudes of prevention program directors and
      frontline staff toward research-based interventions. Characteristics of
      individual respondents as well as organizational characteristics of the ASO
      itself were used to predict perceived benefits of adopting this type of
      intervention, perceived efficacy (confidence) in the ASO's ability to implement
      it, and perceived barriers to adoption. Findings revealed uniformly positive
      perceptions of benefits among respondents from ASOs of different sizes and
      organizational experiences, although directors held more favorable evaluations
      than frontline staff. Respondents from ASOs that were larger, had previously
      delivered group or workshop interventions, or had received outside technical
      assistance in the past expressed more confidence in the ability of their ASO to
      implement the intervention. On the other hand, older and more highly education
      individuals had less confidence in their organization's ability to implement the
      model. Resource constraints (money, staff, and time) were the most common
      barriers cited by the respondents. Overall, higher organizational role and longer
      tenure at an ASO were associated with the perception of more barriers to adopting
      science-based interventions. Respondents from ASOs with a history of receiving
      technical assistance reported fewer perceived barriers. The successful
      dissemination of HIV prevention models from the research arena to the service
      arena will require mechanisms to provide appropriate funding and technical
      assistance, particularly to smaller organizations. Mindful of the resource
      constraints faced by ASOs, researchers can facilitate this process by attempting
      to develop interventions that are less resource- and time-consuming than current
      models.

PMID- 10070592
TI  - Training community members to conduct survey interviews: notes from a study of
      seropositive women.

PMID- 10070593
TI  - [Search for a threshold to distinguish between locoregional and systemic
      reactions using the histamine liberation value and the LTC4 level].
AB  - Allergy to Hymenoptera venom (VH) effects more and more patients in France. It is
      manifest in two main forms, which are Loco-regional (RLR) and Systemic reactions
      (SR). This allergy is detectable amongst others by the techniques of histamine
      release (HR) and release of leucotrienes C4 (LTC4). The aim of this work has been
      to fix a threshold that gives differentiation of RLR ad RS by the two techniques.
      We found in a positive population a threshold histamine release (HR) value of 25%
      and a concentration of LTC4 of 600 ng/ml. These are the thresholds above which a
      patient would be at around 70% risk of RS. This study has a predictive value for
      patients who are suspected of allergy of VH or who have already had clinical
      reactions and risk sensitization.

PMID- 10070594
TI  - [Basophil activation test using flow cytometry in Hymenoptera venom allergy].
AB  - The basophil activation test (TAB) clearly shows evidence to Hymenoptera venoms.
      Comparison of the TAB value with the clinical history allows fixation of a
      threshold that will anticipate the type of clinical reaction by the TAB value.
      For the technique of TAB 3 dilutions are used. The basophil activation values
      produce a threshold for each dilution. For the first dilution the threshold is
      50% activation: below this threshold, 70% of patients would have a local or
      systemic reaction and above this threshold, 70% of patients would have a systemic
      allergic reaction.

PMID- 10070595
TI  - [Hypersensitivity to Anisakis simplex: apropos of 36 cases].
AB  - The authors report a group of 36 cases of hypersensitivity to Anisakis simplex, a
      fish parasite. They examined 11 boys and 25 girls who attended the Allergy
      service of the Central Hospital Marques of Valdecilla in Santander (Spain),
      between 12th May 1997 and 26th June 1998, for history of acute urticaria, most
      often after an aggravation of an allergic pathology. All were given an
      immunological examination that was composed of: food investigation, prick test,
      measurement of total and specific IgE and blood eosinophilia. In conclusion, the
      authors emphasize an increase in hypersensitivity to Anisakis simplex, masked by
      a food allergy and in spite of a nematode infection. Blood eosinophilia was
      normal in most cases.

PMID- 10070596
TI  - [Latex: a complex allergy].
AB  - The authors review several of the most important aspects of latex allergy, an
      increasing problem in Public Health, which should be understood by all health
      professionals. After briefly presenting the history of the origin latex, from
      Hevea brasiliensis the authors describe the antigens of latex: Hev b1 to Hev b8,
      major allergens. They also note the crossed reactivity not only with foods,
      exotic fruits, but also with pneumoallergens and in particular the pollens. The
      groups at risk are essentially workers in the latex industry, health
      professionals and finally infants with spina bifida or other severe urological
      anomaly. The clinical signs are reactions of type 1 hypersensitivity, to
      urticaria and/or angio-oedema and anaphylactic shock. Diagnosis is based on a
      search for specific serum IgE, skin tests and provocation tests. Prophylaxis
      depends on removal of all substances that are based on latex, especially
      replacement of gloves with vinyl, but also on a food diet that excludes all foods
      that have a cross-reactivity with latex.

PMID- 10070597
TI  - [Food allergy to wheat flour in adults].
AB  - Wheat flour is a basic foodstuff. Food allergy has been especially described in
      children, in the form of atopic dermatitis. Food allergy in adults is rare and
      especially described in the form of anaphylactic shock sometimes induced by
      effort. Four observations of adult food allergy are presented. The IgE dependent
      mechanism is documented. The positive oral provocation tests needed doses of 17
      to 30 grams. One crossed sensitivity between rye and barley was seen. The major
      allergen was probably gluten, particularly gliadines. Sensitization was probably
      due to prolonged inhalation of wheat flour. The authors stress the possibility of
      food allergy to wheat flour by other mechanisms, the difficulty of diagnosis,
      needed for a diet without cereal and gluten that is now non reimbursable.

PMID- 10070598
TI  - The effects of respite care on informal carers' well-being: a systematic review.
AB  - PURPOSE: The provision of respite care is a common method employed to reduce the
      burden on those who care for individuals with a chronic illness or disability.
      The aim of the present review was to examine research on respite provision with a
      view to establishing what effect it has on carers. METHOD: A literature search
      was conducted for studies examining the effect of respite provision on carers,
      'Psyclit', 'Medline' and Social Science Citation Index computerized databases
      were utilized, followed by a search of the reference sections of relevant
      studies. RESULTS: The search yielded 29 studies, from which there was little
      evidence that respite intervention has either a consistent or enduring beneficial
      effect on carers' well-being. This may be due in part to the fact that the
      majority of the work conducted has been methodologically poor. Also significant,
      however, might be that the findings suggest respite care often fails to
      facilitate the maintenance of socially supportive relationships, which may
      moderate strain after respite has ended. CONCLUSIONS: A more 'carer-centred'
      approach is required in both the provision and evaluation of respite care
      intervention. This approach would address the experiences of both caregiver and
      care-recipient during the respite period.

PMID- 10070599
TI  - Correlates of exercise maintenance among people with mobility impairments.
AB  - PURPOSE: This paper describes correlates of exercise maintenance in a sample of
      adults with mobility impairments. Understanding processes that promote exercise
      is important if one is to increase access to exercise for people with
      disabilities. METHOD: A model of variables predicting 6-month maintenance of
      regular exercise was examined, using data from a self-administered questionnaire
      given to a community sample of 113 adults with long-term mobility impairments.
      Descriptive analyses and logistic regression were used. RESULTS: Logistic
      regression showed that people with lower motivational barriers and higher
      exercise self-efficacy had a higher probability of exercise maintenance.
      Demographic characteristics and disability-related and environmental barriers did
      not differentiate between those who did and did not continue to exercise.
      CONCLUSIONS: Long-term sustained exercise by people with mobility impairments
      might be promoted by efforts to increase motivation to exercise: involve health
      professionals as one source of support and expand opportunity by increasing
      access to appropriate sites and programming.

PMID- 10070600
TI  - Relationship between traumatic events in childhood and chronic pain.
AB  - PURPOSE: The purpose was to examine the relationships between traumatic events in
      childhood, such as sexual and physical abuse, alcoholism, and drug addiction, and
      three types of chronic pain: facial pain, myofascial pain, and fibromyalgia. A
      fourth group, a heterogeneous group of other pain, was used as a comparison
      group. METHOD: Ninety one patients with chronic pain, age range 20-60, were
      consecutively recruited from the outpatient clinics of a rehabilitation hospital
      and a general hospital. Patients were given four measures for completion at
      evaluation: Childhood History Questionnaire; Childhood Traumatic Events Scale;
      McGill Melzack Pain Questionnaire; Pain Disability Index. Chi-square was used to
      test significant differences among four pain groups on sexual, physical, and
      verbal abuse; alcoholism; drug dependence; medications; major upheaval, childhood
      illness, death of a family member or friend, and separation or divorce of
      parents. Logistic regression was used to predict membership in the four pain
      groups. RESULTS: All pain groups had a history of abuse exceeding 48%:
      fibromyalgia, 64.7%; myofascial, 61.9%; facial, 50%; other pain, 48.3%. All
      groups had a history of family alcohol dependence exceeding 38%, and a history of
      drug dependence ranging from 5.8 to 19.1%. A combined history of pain, child
      physical abuse, and alcoholism was prevalent in 12.9 to 35.3%. Logistic
      regression showed patients who were female, with an alcoholic parent, using non
      narcotic drugs were more likely to be members of the facial, myofascial, and
      fibromyalgia groups. CONCLUSIONS: Child traumatic events are significantly
      related to chronic pain. Since the problem of child abuse is broader than
      physical and sexual abuse, health and rehabilitation agencies must shift from
      individualized treatment to interdisciplinary treatment of the family and
      patient.

PMID- 10070601
TI  - Stroke patients ready for discharge from acute care--a multi-dimensional
      assessment of functions and further care.
AB  - PURPOSE: The aim of this study was to describe actual functions, performance of
      activities and needs of further care in patients with stroke in acute care wards
      at the time the physicians decided that the patients were ready for discharge, in
      relation to placement after discharge and the motives for the decision. METHOD:
      Thus 114 stroke patients in Stockholm County were assessed with the Resident
      Assessment Instrument, and the motives for further care were reviewed in the
      patients' case records. RESULTS: The results showed that the oldest, most
      severely impaired stroke patients had the shortest mean length of stay before the
      physician considered the patients ready for discharge to nursing homes, where
      resources for long-term rehabilitation and stroke care vary. CONCLUSION: It is
      important to secure continuing adequate care and rehabilitation for elderly
      severely impaired stroke patients being discharged early from acute care
      hospitals.

PMID- 10070602
TI  - Evacuation behaviours of occupants with learning difficulties in residential
      homes.
AB  - PURPOSE: This paper reports the results of unannounced evacuation of two
      residential care premises providing accommodation for people with learning
      disabilities. METHOD: Awareness of disability has in relation to fire safety
      focussed generally on mobility. With the advent of performance-based fire safety
      engineering codes which require the characterization of buildings and their
      occupants it is necessary to obtain knowledge of the likely behaviours of people
      with learning difficulties in an emergency. The unannounced evacuations which
      were conducted at 11.30 pm were video recorded to enable observation and an
      analysis of the residents' behaviours. RESULTS AND CONCLUSION: The results and
      observations obtained raise many issues; including transferable training skills,
      predictability of evacuation behaviours, and the need in performance code
      evaluation to consider the characterization of buildings and their occupants as
      mutually inclusive processes.

PMID- 10070603
TI  - Witnessed community violence and antisocial behavior in high-risk, urban boys.
AB  - Examined the longitudinal relation between children's self-report of witnessing
      community violence, family environment, and parent report of child antisocial
      behavior in a sample of 6- to 10-year-old urban American boys (N = 97) at
      familial risk for antisocial behavior. Boys reported high rates of lifetime
      exposure to community violence. Boys' reports of witnessing community violence
      were significantly positively related to changes over 15 months in child
      antisocial behavior, even after controlling for the possible effects of 3 aspects
      of parent-child interactions shown previously to be related to problematic child
      behavior. Furthermore, family environment, particularly the degree to which
      parents engaged in conflict with their sons, moderated the effect of witnessed
      violence on changes in antisocial behavior. In families with low conflict, higher
      levels of witnessed violence predicted increases in antisocial behavior over
      time. In contrast, in families with relatively high levels of parent-child
      conflict, high-witnessed violence had no additional influence on antisocial
      outcome. This is the first prospective longitudinal study to document an
      association between witnessed community violence and changes in antisocial
      behavior in young, urban boys at familial risk for antisocial behavior.

PMID- 10070604
TI  - Marital conflict, family processes, and boys' externalizing behavior in Hispanic
      American and European American families.
AB  - Used self-report and observational measures to explore associations among marital
      conflict, triadic family processes, and child adjustment in Hispanic American,
      European American, and biethnic families. One hundred and thirteen families with
      a 7- to 11-year-old son participated. More similarities than differences were
      found between European American and Hispanic American families. A hierarchical
      parenting style was associated with externalizing behaviors for European American
      and biethnic families but not for Hispanic American families. Marital conflict
      and disengaged family alliances were associated with child externalizing behavior
      for all ethnic groups. Ethnicity was not found to moderate the relation between
      marital conflict and family functioning, and greater levels of marital conflict
      were associated with disengaged family interactions and also with lax or
      inconsistent parenting. Implications for understanding cross-ethnic issues in
      family systems and child adjustment are discussed.

PMID- 10070605
TI  - Social competence and conduct problems in young children: issues in assessment.
AB  - Examined the differences in various facets of social competence in 2 groups of
      young children (ages 4-7 years)--a clinic-referred group of aggressive children
      (N = 60) diagnosed with oppositional defiant disorder or conduct problems and a
      matched comparison group of typically developing children (N = 60). Four aspects
      of social competence were assessed: social information processing, actual
      observations of conflict management skills and social play interactions during
      peer interactions, positive social interactions with mothers and fathers at home,
      and teacher reports of social competence. The social information processing
      assessed included problem-solving skills (hypothetical skills as demonstrated on
      a social problem-solving test), self-perceptions (child's awareness of his or her
      own social self and feelings of loneliness), perceptions of others
      (attributions), and perceptions of others' attitudes toward oneself. To determine
      the construct validity of various means of assessing child social competence, we
      correlated children's social information processing measures with parent and
      teacher reports of social adjustment and with actual observations of interactions
      during peer play and at home with parents. Results comparing the 2 groups suggest
      that young children with conduct problems have deficits in their social
      information processing awareness or interpretation of social cues--they
      overestimate their own social competence and misattribute hostile intent to
      others. Tests of cognitive problem solving and observations of peer play
      interactions indicated that the children with conduct problems had significantly
      fewer positive problem-solving strategies and positive social skills, more
      negative conflict management strategies, and delayed play skills with peers than
      the comparison children. Correlation analyses indicated significant correlations
      between children's negative attributions and the ratio of positive to negative
      problem-solving strategies with observations of peer play interactions.

PMID- 10070606
TI  - Diagnostic status and symptomatic behavior of hard-to-manage preschool children
      in middle childhood and early adolescence.
AB  - Followed 2 cohorts of hard-to-manage preschool children and comparison children
      without early problems to middle childhood and early adolescence. Children with
      early problems, especially problems that were still evident at school entry, were
      more likely to meet diagnostic criteria for an externalizing diagnosis at follow
      up. Hard-to-manage children in Cohort 1 with problems that persisted from ages 3
      through 9 years were much more likely to meet diagnostic criteria at age 13 than
      children whose early problems were less stable in elementary school. Similarly,
      hard-to-manage boys in Cohort 2 whose problems persisted at age 6 were more
      likely to meet criteria for an externalizing diagnosis at age 9 than hard-to
      manage boys whose problems appeared less stable at age 6. Across cohorts,
      children with persistent problems had higher levels of symptoms and more varied
      symptoms at ages 3 and 4 and over the course of development.

PMID- 10070607
TI  - Attachment behavior and its antecedents in offspring born to methadone-maintained
      women.
AB  - Videotaped 35 full-term, African American infants exposed in utero to methadone
      and 46 comparison infants at 12 months participating in a separation-reunion
      procedure to assess aspects of the infant's attachment relationship to the
      mother. Mothers in the two groups were comparable on education, age (18-35
      years), socioeconomic status, parity, IQ and marital status. Offspring born to
      methadone-maintained women did not differ from comparison infants in indexes of
      proximity-seeking at reunion but did display higher scores on indexes of
      disorganized and avoidant behavior and lower scores on indexes of contact
      maintaining behavior. Mothers' perceptions during pregnancy of their future
      infants' degree of bothersomeness were also related to higher scores on contact
      maintaining behavior and lower scores on avoidant behavior. Finally, antecedents
      of attachment behavior within the opioid group alone were considered. The
      implications of using dimensional attachment ratings for uncovering more subtle
      attachment antecedents are discussed.

PMID- 10070608
TI  - The pediatric emotional distress scale: a brief screening measure for young
      children exposed to traumatic events.
AB  - Introduced the Pediatric Emotional Distress Scale (PEDS), which was developed to
      quickly assess behaviors identified in empirical and theoretical literature as
      significantly elevated in children after experiencing traumatic events. The 21
      item parent-report rating scale includes 17 general behavior items and 4 trauma
      specific items. Factor analyses on the 17 items, with 475 two- to ten-year-olds
      (traumatic event exposure and nontraumatic event exposure), yielded 3 reliable
      factors labeled Anxious/Withdrawn, Fearful, and Acting Out. Factor and total
      scores were shown to have good internal consistency, and both test-retest and
      interrater reliability were at acceptable levels. Discriminant analyses
      demonstrated the PEDS could distinguish traumatic event exposure and nonexposure
      groups, although maternal education should be a significant consideration in
      interpretation. Future research with diverse populations who have documented
      trauma is needed to enhance the utility of the full PEDS scale.

PMID- 10070609
TI  - Differentiating anxious and depressive self-statements in youth: factor structure
      of the Negative Affect Self-Statement Questionnaire among youth referred to an
      anxiety disorders clinic.
AB  - Conducted a factor analysis on the items from the Negative Affect Self-Statement
      Questionnaire (NASSQ; Ronan, Kendall, & Rowe, 1994). This analysis yielded 4
      factors (Depressive Self-Statements, Anxiety/Somatic Self-Statements, Negative
      Affect Self-Statements, and Positive Affect Self-Statements) broadly consistent
      with both the content-specificity hypothesis (Beck & Clark, 1988) and L. A. Clark
      and Watson's (1991b) tripartite model of anxiety and depression. The association
      between children's self-talk and measures of trait anxiety and depression was
      also examined. Self-statements with content theoretically specific to depression
      were the best predictors of self-reported depressive symptoms, but the results
      were less clear for trait anxiety. Overall, these results provide evidence for
      the discriminability of anxious and depressive self-talk in youth and for the
      utility of the NASSQ as a cognitive assessment instrument.

PMID- 10070610
TI  - Predicting dysphoria in adolescence from actual and perceived peer acceptance in
      childhood.
AB  - Predicted dysphoria in midadolescence using actual and perceived peer acceptance
      of 68 4th and 5th graders (48% male, 30% minority). Main effect, additive, and
      interactive models for predicting dysphoria were examined. Perceived acceptance
      predicted later dysphoria, after controlling for initial levels of dysphoria,
      supporting the main effect model. Actual acceptance did not uniquely contribute
      to prediction of later dysphoria, and actual acceptance did not moderate the
      prediction of dysphoria from perceived acceptance. Sex differences in dysphoria
      were significant, but sex did not moderate the predictive links between perceived
      acceptance and dysphoria.

PMID- 10070611
TI  - Behavioral validation of the Childhood Anxiety Sensitivity Index in children.
AB  - Examined the construct validity of the Childhood Anxiety Sensitivity Index (CASI)
      in young children through the use of a behavioral challenge task. Elementary
      school children completed the CASI as well as self-report measures of state and
      trait anxiety and subjective fear prior to and immediately following a stair
      stepping task designed to increase physiological arousal. Results indicate that
      the CASI was a significant predictor of the degree of state anxiety and
      subjective fear reported in response to the challenge task, even after
      controlling for pretask levels of state anxiety and fear, respectively.
      Additionally, the CASI predicted changes in fear experienced in response to the
      challenge task. The findings lend support to the validity of the CASI in
      preadolescent children and suggest that the CASI possesses unique clinical
      utility relative to measures of trait anxiety. However, results of this study
      must be interpreted cautiously, because a large portion of the variance in
      response to arousal was left unaccounted for by the CASI and the overall model.

PMID- 10070612
TI  - 3-Methylglutaconic aciduria type I: clinical heterogeneity as a neurometabolic
      disease.
AB  - 3-Methylglutaconic (3-MGC) aciduria with 3-methylglutaconyl-CoA hydratase
      deficiency (3-MGC aciduria type I) is a rare inherited metabolic disease of L
      leucine catabolism. We describe a 9-month-old Japanese boy with this disorder who
      showed progressive neurological impairments presented as quadriplegia, athetoid
      movements and severe psychomotor retardation from 4 months of age. This finding
      indicates the existence of clinical heterogeneity in 3-MGC aciduria type I,
      suggesting it may present as a neurometabolic disease.

PMID- 10070613
TI  - Identification of new medium-chain acylcarnitines present in urine of a patient
      with medium-chain acyl-CoA dehydrogenase deficiency.
AB  - Previously undescribed medium-chain acylcarnitines were identified in a urine
      sample from a patient with medium-chain acyl-CoA dehydrogenase deficiency. These
      are the 4-methylvaleryl, 4- and 5-methylhexanoyl, 6-methylheptanoyl-, 6
      methyloctanoyl-, 4,5-dimethylhexanoyl- and 4,7-decadienoylcarnitines. Their
      chemical structures were obtained by gas chromatographymass spectrometry analysis
      of their fatty acid moieties as picolinyl esters.

PMID- 10070614
TI  - The human NADH: ubiquinone oxidoreductase NDUFS5 (15 kDa) subunit: cDNA cloning,
      chromosomal localization, tissue distribution and the absence of mutations in
      isolated complex I-deficient patients.
AB  - We have cloned the cDNA of the NDUFS5 subunit (15 kDa) of the human mitochondrial
      respiratory chain complex NADH: ubiquinone oxidoreductase (complex I). The open
      reading frame consists of 321 base-pairs, coding for 106 amino acids, with a
      calculated molecular mass of 12.5 kDa. There is an 81.0% identity with the bovine
      equivalent on cDNA level and 74.5% identity on amino acid basis. PCR analysis of
      rodent-human somatic cell hybrids revealed that the human NDUFS5 gene maps to
      chromosome 1. The NDUFS5 mRNA is expressed ubiquitously in human tissues, with a
      relative higher expression in human heart, skeletal muscle, liver, kidney and
      fetal heart. A mutation detection study of twenty isolated enzymatic complex I
      deficient patients revealed no mutations, nor polymorphisms.

PMID- 10070615
TI  - Transport of phytanic acid on lipoproteins in Refsum disease.
AB  - Patients with Refsum disease accumulate significant quantities of phytanic acid
      in adipose and neural tissue. The accumulation can be reversed by following a
      diet low in phytanic acid, yet the mechanism of transport of this fatty acid is
      obscure. We investigated the distribution of phytanic acid in different
      lipoprotein subfractions in 11 patients with Refsum disease and 9 unaffected
      siblings. Plasma phytanic acid was distributed on VLDL (16.2% +/- 12.2%), IDL
      (1.77% +/- 1.64%), LDL (34.8% +/- 12.6%) and HDL (14.3% +/- 7.87%). No
      correlations with any parameter were seen with total phytanic acid content. Weak
      nonsignificant correlations were found with the fractional distribution of
      phytanic acid and VLDL triglyceride (r = 0.35; p = 0.12) and plasma HDL
      cholesterol (r = 0.32; p = 0.16) and with LDL:HDL cholesterol ratio (r = 0.33; p
      = 0.14). Significant correlation of the fractional distribution of phytanic acid
      on lipoprotein particles was noted with the ratio of apolipoprotein B:
      apolipoprotein A1-containing particles (r = 0.46; p = 0.03) and apolipoprotein B:
      apolipoprotein A1 in HDL2 (r = 0.53; p = 0.01). This suggests that the import
      export balance for phytanic acid in plasma is related to forward and reverse
      cholesterol transport on lipoprotein particles, and only weakly to plasma
      cholesterol and triglycerides. These ratios of apolipoprotein particles may play
      a significant role in determining the rate of phytanic acid elimination in
      patients with Refsum disease.

PMID- 10070616
TI  - The molecular basis of transferase galactosaemia in South African negroids.
AB  - Transferase galactosaemia is an autosomal recessively inherited disorder caused
      by a deficiency of galactose-1-phosphate uridyltransferase (GALT). Manifestations
      include jaundice, vomiting, cataracts, mental retardation, speech abnormalities
      and poor growth. The GALT gene has been mapped and sequenced. The S135L mutation
      accounts for approximately 48% of galactosaemia alleles in African Americans and
      has been found to account for about 91% of galactosaemia alleles in negroid South
      African patients which suggested that the mutation had an African origin. We have
      calculated the S135L allele frequency (+/- 1SE) in a sample of healthy unrelated
      negroid South Africans to be 0.0067 (+/- 0.0024). The S135L mutation was also
      detected in negroid populations from other regions of Africa confirming its
      African origin.

PMID- 10070617
TI  - Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen
      storage disease type Ia.
AB  - Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic
      disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning
      of the G6Pase gene and the subsequent identification of several disease-causing
      mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and
      DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian
      patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of
      the mutant alleles. Eight novel mutations and three rare mutations were
      identified in 15.7% of disease alleles. These results suggest that a DNA-based
      method can be used as an initial screening in Italian patients clinically
      suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In
      particular, a noninvasive diagnosis is a suitable method for the Italian
      subpopulation coming from Sicily, where the R83C mutation is present in 80% of
      mutant alleles. Molecular carrier detection and prenatal diagnosis can be
      provided to GSD1a families with identified mutation in the propositus.

PMID- 10070618
TI  - Bone marrow transplantation for Maroteaux-Lamy syndrome (MPS VI): long-term
      follow-up.
AB  - We describe the results of bone marrow transplantation (BMT) in four patients
      with mucopolysaccharidosis type VI (MPS VI, McKusick 253200)--Maroteaux-Lamy
      disease. The indications for transplantation were cardiomyopathy in three
      patients and severe obstructive sleep apnoea in one. The follow-up period ranges
      between 1 and 9 years, and three of the patients are at mainstream schools. In
      all of the patients the facial features have become less coarse and the cardiac
      manifestations have improved or remained stable. However, skeletal changes have
      persisted or even progressed, although posture and joint mobility have improved
      and all the patients have remained ambulatory and active. BMT appears to prolong
      survival and improve the quality of life in MPS VI patients, but careful
      selection of patients is essential.

PMID- 10070619
TI  - Severe skeletal complications in Japanese patients with type 1 Gaucher disease.
AB  - To better characterize skeletal complications in Japanese patients with type 1
      Gaucher disease (GD), we performed genotyping and clinical and radiological
      analysis of 35 patients, the vast majority of this population, Skeletal
      complications tend to be very common, severe and rapidly progressive in Japanese
      patients with type 1 GD. Twenty (57%) of these patients manifested end points of
      severe bone disease including avascular necrosis, pathological fracture and/or
      bone crisis. Mean time from presentation/diagnosis of GD until presentation of
      this involvement was 3 years 6 months +/- 4 years 1 month. Prevalence of severe
      bone disease is significantly higher in splenectomized than in non-splenectomized
      patients--81% (17/21) versus 21% (3/14) (p = 0.0007, Fisher's exact test). Four
      (29%) of 14 patients receiving enzyme replacement therapy (ERT) or bone marrow
      transplantation (BMT) manifested severe bone involvement for the first time
      during or after treatment. All cases occurred in children in whom ERT doses had
      been lowered after only brief administration of higher starting doses (n = 3) or
      partial donor marrow engraftment resulted in low glucocerebrosidase (GCR)
      activity (n = 1). These observations suggest that splenectomy may correlate with
      accelerated skeletal deterioration with severe skeletal disease, at least in
      patients with severe phenotypic expression. They also suggest that it is
      important that sufficient GCR is available in paediatric patients with severe
      phenotypic expression. Hence ERT dosages should be based on disease severity and
      on age, with sustained administration of full doses in patients at greater risk
      of important skeletal complications.

PMID- 10070620
TI  - Pilot study of screening for Wilson disease using dried blood spots obtained from
      children seen at outpatient clinics.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper accumulation
      leading to liver and/or brain damage. In this paper, we describe the results of a
      pilot study of screening for WD using ceruloplasmin determinations in dried blood
      samples. Specimens were collected from children aged 1 to 6 years who were seen
      at local paediatric outpatient clinics in the Miyagi Prefecture. We measured
      ceruloplasmin (CP) concentrations in 2789 children using an enzyme-linked
      immunosorbent assay. The mean value was 12.4 +/- 3.95 mg/dl blood. Among these
      children, we identified two (case 1, male, 2 years old; case 2, female, 3 years
      old) with markedly reduced CP concentrations. Apart from low serum copper
      concentrations, their biochemical findings were almost normal, as were growth and
      development. To confirm the diagnosis, we analysed the WD gene and detected
      A803T/2871delC mutations in case 1 and R778L/G1035V mutations in case 2. We
      conclude that these children were presymptomatic WD patients. The CP level in
      dried blood samples from children aged 1 to 6 years appears to be a reliable
      marker for early detection of WD.

PMID- 10070621
TI  - Pyloric stenosis in a boy with non-ketotic hyperglycinaemia.

PMID- 10070622
TI  - Prenatal molecular diagnosis of severe ornithine carbamoyltransferase deficiency
      due to a novel mutation, E181G.

PMID- 10070623
TI  - An adult with a non-neuronopathic form of Niemann-Pick C disease.

PMID- 10070624
TI  - Aplastic anaemia in association with Kearns-Sayre syndrome.

PMID- 10070625
TI  - Normal acylcarnitines in maternal urine during a pregnancy affected by glutaric
      aciduria type II.

PMID- 10070626
TI  - The ND1 T3308C mutation may be a mtDNA polymorphism. Report of two Portuguese
      patients.

PMID- 10070627
TI  - Three novel and one recurrent ornithine carbamoyltransferase gene mutations in
      Polish patients.

PMID- 10070628
TI  - Fatal genetic defect causing Wolman disease.

PMID- 10070629
TI  - Red-cell thiamine pyrophosphate levels in hypophosphatasia.

PMID- 10070630
TI  - Euthanasia in The Netherlands--down the slippery slope?

PMID- 10070631
TI  - Medicalised erections on demand?

PMID- 10070632
TI  - Assessment of physician-assisted death by members of the public prosecution in
      The Netherlands.
AB  - OBJECTIVES: To identify the factors that influence the assessment of reported
      cases of physician-assisted death by members of the public prosecution.
      DESIGN/SETTING: At the beginning of 1996, during verbal interviews, 12 short case
      descriptions were presented to a representative group of 47 members of the public
      prosecution in the Netherlands. RESULTS: Assessment varied considerably between
      respondents. Some respondents made more "lenient" assessments than others.
      Characteristics of the respondents, such as function, personal-life philosophy
      and age, were not related to the assessment. Case characteristics, i.e. the
      presence of an explicit request, life expectancy and the type of suffering,
      strongly influenced the assessment. Of these characteristics, the presence or
      absence of an explicit request was the most important determinant of the decision
      whether or not to hold an inquest. CONCLUSIONS: Although the presence of an
      explicit request, life expectancy and the type of suffering each influenced the
      assessment, each individual assessment was dependent on the assessor. The
      resulting danger of legal inequality and legal uncertainty, particularly in
      complicated cases, should be kept to a minimum by the introduction of some form
      of protocol and consultation in doubtful or boundary cases. The notification
      procedure already promotes a certain degree of uniformity in the prosecution
      policy.

PMID- 10070633
TI  - Voluntary euthanasia under control? Further empirical evidence from The
      Netherlands.
AB  - Nineteen ninety-six saw the publication of a major Dutch survey into euthanasia
      in the Netherlands. This paper outlines the main statistical findings of this
      survey and considers whether it shows that voluntary euthanasia is under
      effective control in the Netherlands. The paper concludes that although there has
      been some improvement in compliance with procedural requirements, the practice of
      voluntary euthanasia remains beyond effective control.

PMID- 10070634
TI  - Slippery slopes in flat countries--a response.
AB  - In response to the paper by Keown and Jochemsen in which the latest empirical
      data concerning euthanasia and other end-of-life decisions in the Netherlands is
      discussed, this paper discusses three points. The use of euthanasia in cases in
      which palliative care was a viable alternative may be taken as proof of a
      slippery slope. However, it could also be interpreted as an indication of a shift
      towards more autonomy-based end-of-life decisions. The cases of non-voluntary
      euthanasia are a serious problem in the Netherlands and they are only rarely
      justifiable. However, they do not prove the existence of a slippery slope.
      Persuading the physician to bring euthanasia cases to the knowledge of the
      authorities is a problem of any euthanasia policy. The Dutch notification
      procedure has recently been changed to reduce the underreporting of cases.
      However, many questions remain.

PMID- 10070635
TI  - Conditions required for a law on active voluntary euthanasia: a survey of nurses'
      opinions in the Australian Capital Territory.
AB  - OBJECTIVES: To ascertain which conditions nurses believe should be in a law
      allowing active voluntary euthanasia (AVE). DESIGN: Survey questionnaire posted
      to registered nurses (RNs). SETTING: Australian Capital Territory (ACT) at the
      end of 1996, when active voluntary euthanasia was legal in the Northern
      Territory. SURVEY SAMPLE: A random sample of 2,000 RNs, representing 54 per cent
      of the RN population in the ACT. MAIN MEASURES: Two methods were used to look at
      nurses' opinions. The first involved four vignettes which varied in terms of
      critical characteristics of each patient who was requesting help to die. The
      respondents were asked if the law should be changed to allow any of these
      requests. There was also a checklist of conditions, most of which have commonly
      been included in Australian proposed laws on AVE. The respondents chose those
      which they believed should apply in a law on AVE. RESULTS: The response rate was
      61%. Support for a change in the law to allow AVE was 38% for a young man with
      AIDS, 39% for an elderly man with early stage Alzheimer's disease, 44% for a
      young woman who had become quadriplegic and 71% for a middle-aged woman with
      metastases from breast cancer. The conditions most strongly supported in any
      future AVE law were: "second doctor's opinion", "cooling off period", "unbearable
      protracted suffering", "patient fully informed about illness and treatment" and
      "terminally ill". There was only minority support for "not suffering from
      treatable depression", "administer the fatal dose themselves" and "over a certain
      age". CONCLUSION: Given the lack of support for some conditions included in
      proposed AVE laws, there needs to be further debate about the conditions required
      in any future AVE bills.

PMID- 10070636
TI  - Selecting subjects for participation in clinical research: one sphere of justice.
AB  - Recent guidelines from the US National Institutes of Health (NIH) mandate the
      inclusion of adequate numbers of women in clinical trials. Ought such standards
      to apply internationally? Walzer's theory of justice is brought to bear on the
      problem, the first use of the theory in research ethics, and it argues for broad
      application of the principle of adequate representation. A number of practical
      conclusions for research ethics committees (RECs) are outlined. Eligibility
      criteria in clinical trials ought to be justified by trial designers. Research
      ethics committees ought to question criteria that seem to exclude unnecessarily
      women from research participation. The issue of adequate representation should be
      construed broadly, so as to include consideration of the representation of the
      elderly, persons with HIV, mental illness and substance abuse disorders in
      clinical research.

PMID- 10070637
TI  - Relationships between various attitudes towards self-determination in health care
      with special reference to an advance directive.
AB  - OBJECTIVES: The subject of patient self-determination in health care has gained
      broad interest because of the increasing number of incompetent patients. In an
      attempt to solve the problems related to doctors' decision making in such
      circumstances, advance directives have been developed. The purpose of this study
      was to examine relationships between public attitudes towards patient autonomy
      and advance directives. SUBJECTS AND MAIN OUTCOME MEASURES: A stratified random
      sample of 600 adults in northern Sweden was surveyed by a questionnaire with a
      response rate of 78.2%. The subjects were asked about their wish for control of
      their health care, their concerns about health care, their treatment preferences
      in a life-threatening situation (both reversible and irreversible), and their
      attitudes towards the application of advance directives. RESULTS: Numerous
      relationships between various aspects of self-determination in health care
      (desire for control, fears of over-treatment, and choice of treatment level) in
      general and advance directives, in particular, were found. Those who wanted to
      have a say in their health care (about 94%) also mainly supported the use of an
      advance directive. CONCLUSIONS: The fact that almost 30% of the respondents were
      undecided concerning their personal use of advance directives points to a lack of
      knowledge and to the necessity of education of the public on these issues.

PMID- 10070638
TI  - Do case studies mislead about the nature of reality?
AB  - This paper attempts a partial, critical look at the construction and use of case
      studies in ethics education. It argues that the authors and users of case studies
      are often insufficiently aware of the literary nature of these artefacts: this
      may lead to some confusion between fiction and reality. Issues of the nature of
      the genre, the fictional, story-constructing aspect of case studies, the nature
      of authorship, and the purposes and uses of case studies as "texts" are outlined
      and discussed. The paper concludes with some critical questions that can be
      applied to the construction and use of case studies in the light of the foregoing
      analysis.

PMID- 10070639
TI  - Do studies of the nature of cases mislead about the reality of cases? A response
      to Pattison et al.
AB  - This article questions whether many are misled by current case studies. Three
      broad types of style of case study are described. A stark style, based on medical
      case studies, a fictionalised style in reaction, and a personal statement made in
      discussion groups by an original protagonist. Only the second type fits
      Pattison's category. Language remains an important issue, but to be examined as
      the case is lived in discussion rather than as a potentially reductionist study
      of the case as text.

PMID- 10070640
TI  - How physician executives and clinicians perceive ethical issues in Saudi Arabian
      hospitals.
AB  - OBJECTIVES: To compare the perceptions of physician executives and clinicians
      regarding ethical issues in Saudi Arabian hospitals and the attributes that might
      lead to the existence of these ethical issues. DESIGN: Self-completion
      questionnaire administered from February to July 1997. SETTING: Different health
      regions in the Kingdom of Saudi Arabia. PARTICIPANTS: Random sample of 457
      physicians (317 clinicians and 140 physician executives) from several hospitals
      in various regions across the kingdom. RESULTS: There were statistically
      significant differences in the perceptions of physician executives and clinicians
      regarding the existence of various ethical issues in their hospitals. The vast
      majority of physician executives did not perceive that seven of the eight issues
      addressed by the study were ethical concerns in their hospitals. However, the
      majority of the clinicians perceived that six of the same eight issues were
      ethical considerations in their hospitals. Statistically significant differences
      in the perceptions of physician executives and clinicians were observed in only
      three out of eight attributes that might possibly lead to the existence of
      ethical issues. The most significant attribute that was perceived to result in
      ethical issues was that of hospitals having a multinational staff. CONCLUSION:
      The study calls for the formulation of a code of ethics that will address
      specifically the physicians who work in the kingdom of Saudi Arabia. As a more
      immediate initiative, it is recommended that seminars and workshops be conducted
      to provide physicians with an opportunity to discuss the ethical dilemmas they
      face in their medical practice.

PMID- 10070641
TI  - Best interests in persistent vegetative state.

PMID- 10070642
TI  - Euthanasia in The Netherlands.

PMID- 10070643
TI  - Greek theories on eugenics.

PMID- 10070644
TI  - Students' opinions on the medical ethics course in the medical school curriculum.

PMID- 10070645
TI  - Imperialism, research ethics and global health.

PMID- 10070646
TI  - Medical research needs lay involvement.

PMID- 10070647
TI  - The buck stops here.

PMID- 10070648
TI  - Access to health care resources for family caregivers of elderly persons with
      dementia.
AB  - Concerns about the "elder care crisis" and changes in the provision of health
      care are fostering expectations that families should be responsible for taking
      care of their elderly members. The assumptions that families (1) are not
      providing enough care, (2) know how to provide care, and (3) have access to
      resources for the provision of care are embedded in the social expectation of
      family care for elderly persons with dementia. However, research shows that these
      assumptions are not based on fact.

PMID- 10070649
TI  - Purchasing population health: aligning financial incentives to improve health
      outcomes.
AB  - OBJECTIVE: To review the concept of population health, including its definition,
      measurement, and determinants, and to suggest an approach for aligning financial
      incentives toward this goal. DATA SOURCE, STUDY DESIGN, DATA EXTRACTION:
      Literature review, policy analysis PRINCIPAL FINDINGS: The article presents the
      argument that a major reason for our slow progress toward health outcome
      improvement is that there is no operational definition of population health and
      that financial incentives are not aligned to this goal. Current attempts at
      process measures as indicators of quality or outcome are not adequate for the
      task. It is suggested that some measure of health-adjusted life expectancy be
      adopted for this purpose, and that integrated delivery systems and other agents
      responsible for nonmedical determinants be rewarded for improvement in this
      measure. This will require the development of an investment portfolio across the
      determinants of health based on relative marginal return to health, with
      horizontal integration strategies across sectoral boundaries. A 20-year three
      phase development strategy is proposed, including components of research and
      acceptance, integrated health system implementation, and cross-sectoral
      integration. CONCLUSIONS: The U.S. health care system is a $1 trillion industry
      without a definition of its product. Until population outcome measures are
      developed and rewarded for, we will not solve the twenty-first century challenge
      of maximizing health outcome improvement for the resources available.

PMID- 10070650
TI  - Fulfilling regional needs for specialty nurses through limited-cohort graduate
      education.
AB  - The University of Minnesota has developed a limited-cohort distance education
      graduate program to overcome geographic barriers and address the shortage of
      master's-prepared specialty nurses in rural areas of the upper Midwest. Such a
      program offers graduate nursing education in various specialty areas to distance
      sites for a predetermined, relatively short period.

PMID- 10070651
TI  - Providing culturally competent care: is there a role for health promoters?
AB  - To bridge the widening gap between clients of varied cultural backgrounds and the
      biomedical system in which nurses practice, nurses should foster the inclusion of
      health promoters in selected health care settings. Health promoters, who are
      persons of the same racial or ethnic background as the clients they serve, can
      help form a link between their community and the dominant health care system.

PMID- 10070652
TI  - Association of Women's Health, Obstetric and Neonatal Nurses' Health for Women
      and Newborns Program.

PMID- 10070653
TI  - Living longer, dying longer: nursing's opportunity to make a difference.

PMID- 10070654
TI  - American Academy of Nursing's Women's Health Expert Panel Recommendations for
      Women's Health and Women's Health Care.

PMID- 10070655
TI  - Seasonal dynamics of Pneumocystis carinii in the field vole, Microtus agrestis,
      and in the common shrew, Sorex araneus, in Finland.
AB  - Seasonal dynamics of Pneumocystis carinii in the field vole, Microtus agrestis,
      and in the common shrew, Sorex araneus, were investigated in southern and central
      Finland by microscopical examination of methenamine silver-stained tissue
      sections. In both host species at both localities the number of P. carinii cyst
      forms was highest in late autumn (November). In S. araneus, prevalence was higher
      than in M. agrestis during all seasons. None of the animals was heavily infected
      or apparently ill, and neither species showed any extrapulmonary dissemination.
      In this study covering an increase phase and 4 peak host-density phases of the
      vole cycle, the occurrence of P. carinii seemed to be related to the population
      density of M. agrestis.

PMID- 10070656
TI  - Treatment with recombinant human tumour necrosis factor-alpha reduces
      parasitaemia and prevents Plasmodium berghei K173-induced experimental cerebral
      malaria in mice.
AB  - The present study shows that treatment with recombinant human tumour necrosis
      factor-alpha (rhTNF-alpha) can suppress parasitaemia and prevents development of
      experimental cerebral malaria (ECM) in Plasmodium berghei K173-infected mice.
      Mice received rhTNF-alpha treatment either by subcutaneous injection of free or
      liposome-encapsulated rhTNF-alpha or sustained intraperitoneal administration of
      rhTNF-alpha given via mini-osmotic pumps. Low-dose treatment with a subcutaneous
      bolus injection of rhTNF-alpha protected against ECM when treatment was started
      on day 5 or 6 after infection. The same protective efficacy was obtained either
      by subcutaneous injection of liposome-encapsulated rhTNF-alpha or by sustained
      release from osmotic pumps, but in the latter case a 10-fold lower daily dose of
      rhTNF-alpha was sufficient. Treatment with rhTNF-alpha substantially suppressed
      parasitaemia in ECM-protected mice, but not in mice developing ECM. Thus, the
      rhTNF-alpha mediated suppression of parasitaemia is directly or indirectly
      involved in protection against ECM. Sustained delivery of rhTNF-alpha through
      osmotic pumps, but not by subcutaneous injection of liposome-encapsulated rhTNF
      alpha, resulted in increased concentrations of soluble mouse TNF receptor R75
      (sTNFR75) in plasma at day 9 after infection when non-treated mice die of ECM.
      Thus, protection against ECM is not directly correlated with the sTNFR75
      concentrations at day 9 after infection.

PMID- 10070657
TI  - Purification and immunocytochemical localization of neuraminidase from
      Tritrichomonas foetus.
AB  - Lysis of Tritrichomonas foetus with a solution of the non-ionic detergent Triton
      X-114 at 0 degree C, followed by low-speed centrifugation, resulted in a
      detergent-insoluble pellet and a detergent-soluble supernatant. The supernatant
      was further fractionated by phase separation at 30 degrees C into a detergent
      rich phase and an aqueous phase. Neuraminidase activity was mostly located in the
      detergent-insoluble pellet. When the parasites were incubated with bacterial
      phosphatidylinositol phospholipase C (PI-PLC) prior to detergent solubilization
      and phase separation neuraminidase activity was predominantly recovered in
      aqueous phase, rather than in the pellet and detergent phase. The molecular mass
      determined by gel permeation in high performance liquid chromatography (HPLC) and
      SDS-PAGE was 80,000 Da. Indirect immunofluorescence microscopy using polyclonal
      antibodies raised in rabbits against the purified neuraminidase, indicated that
      the enzyme is exposed on the cell surface. Previous treatment of the cells with
      PI-PLC significantly reduced antibody binding. Incubation of cryo-sections with
      the antibodies followed by detection using gold-labelled anti-rabbit IgG
      confirmed the presence of neuraminidase in the plasma membrane enclosing the cell
      body and flagella and in the membrane of vesicles preferentially located at the
      peripheral region of the protozoan.

PMID- 10070658
TI  - Detection of Leishmania lipophosphoglycan binding proteins in the gut of the
      sandfly vector.
AB  - Binding to the midgut microvillar surface in the sandfly Phlebotomus papatasi is
      a prerequisite for successful development of Leishmania major within the gut of
      the vector. This paper describes a method for detecting microvillar-associated
      proteins which act as ligands for the parasite surface glycoconjugate
      lipophosphoglycan (LPG). Adhesion of LPG to midgut proteins was visualized by
      probing midgut extracts with LPG using a Western ligand blotting technique.
      Procyclic L. major LPG bound to a microvillar polypeptide band of 65 kDa
      (estimated in the non-reduced state) and bound variably to several lower
      molecular weight bands, probably degradation products or subunits of the primary
      binding polypeptides. Specificity of binding was confirmed by co-incubating
      biotinylated LPG with an LPG-specific mAb which resulted in a great reduction in
      binding.

PMID- 10070659
TI  - Transmission of Borrelia afzelii from Apodemus mice and Clethrionomys voles to
      Ixodes ricinus ticks: differential transmission pattern and overwintering
      maintenance.
AB  - This study deals with the ecology of Lyme borreliosis in Europe. The
      relationships between Borrelia burgdorferi sensu lato spirochetes, Clethrionomys
      and Apodemus rodent reservoirs and the Ixodes ricinus tick vector were
      investigated during 16 consecutive months in an enzootic area in Switzerland.
      Cultivation of ear skin biopsies was used to isolate spirochetes from C.
      glareolus, A. sylvaticus, A. flavicollis and Glis glis. Borrelia infection was
      more frequently observed in Clethrionomys than in Apodemus. Tick xenodiagnosis
      was used to determine the infectivity of rodents. The infection rate in ticks fed
      on Clethrionomys was higher than that in ticks fed on Apodemus, but Apodemus
      yielded more infected ticks than Clethrionomys because of a better tick moulting
      success. Xenodiagnostic ticks were placed into BSK medium to obtain isolates.
      Isolates from rodents and rodent-feeding ticks were all identified as B. afzelii.
      The follow-up of the infectivity status of repeatedly recaptured rodents clearly
      demonstrated that these hosts remained infective for ticks during winter till the
      following spring. Comparing C. glareolus and A. sylvaticus, each rodent species
      showed different host infection, different host infectivity and contributed
      differently to the moulting success of feeding ticks. These factors influence
      differentially the pattern of transmission of B. afzelii from Clethrionomys voles
      and Apodemus mice to I. ricinus ticks.

PMID- 10070660
TI  - Segregation of a microsporidian parasite during host cell mitosis.
AB  - We investigated the segregation of an intracellular microsporidian parasite
      during host cell division. A time-course experiment was carried out to examine
      the distribution of parasites relative to host chromosomal DNA via light and
      electron microscopy. Fluorescent light microscopy and EM studies showed that the
      parasite lay in the perinuclear zone of the host cell during interphase and
      segregated to daughter cells at mitosis. At metaphase, the parasite was
      frequently closely associated with host microtubules and mitochondria. Electron
      dense bridges were observed between the parasites and the host microtubules and
      also between host mitochondria and microtubules. The study suggests that both the
      parasite and the host cell organelles segregate in association with spindle
      microtubules.

PMID- 10070661
TI  - Sequence and PCR-RFLP analysis of the internal transcribed spacers of the rDNA
      repeat unit in isolates of Cryptosporidium from different hosts.
AB  - The Cryptosporidium ITS1, 5.8S and ITS2 rDNA regions from a number of
      Cryptosporidium isolates from different hosts and geographical areas were cloned
      and sequenced in order to investigate the extent of sequence heterogeneity
      between human and cattle-derived isolates from different geographical locations
      and also between isolates of Cryptosporidium from different hosts such as cats,
      pigs, mice and a koala. Calf-derived isolates from different continents were
      virtually identical as were human-derived isolates from the UK and Australia.
      Genetic differences between Cryptosporidium isolates were extensive and were in
      fact greater than the level of nucleotide divergence between Toxoplasma gondii
      and Neospora caninum rDNA sequences. Based on the sequence information derived
      from this study, PCR-RFLP of the ITS1 region was undertaken in order to directly
      amplify and genotype Cryptosporidium isolates from different hosts. This PCR-RFLP
      approach can now be used for molecular epidemiology studies, circumventing the
      need for costly sequencing and allowing a wider range of genetically different
      isolates to be examined.

PMID- 10070662
TI  - Sarcocystis species in skeletal muscle of otter (Lutra lutra).
AB  - Cysts of a Sarcocystis species were found in large numbers in skeletal muscle of
      an otter (Lutra lutra) which was raised in Norway and died in captivity in
      Sweden. This is the first report of Sarcocystis infection in the otter. The
      sarcocysts were 0.3-2.3 mm long and 0.06-0.25 mm wide. As judged by light
      microscopy the sarcocyst walls were thin (< 3 microns) with a serrated surface
      but without visible projections. By transmission electron microscopy, the
      sarcocyst wall measured 0.6-1.8 microns and had minute undulations covering the
      entire sarcocyst surface giving the wall a wavy appearance. Septa were
      indistinct. The sarcocysts contained few metrocytes and numerous bradyzoites.
      Sarcocysts were not found in 69 other otters subjected to necropsy in Sweden.

PMID- 10070663
TI  - Breeding systems in Echinococcus granulosus (Cestoda; Taeniidae): selfing or
      outcrossing?
AB  - We used the PCR-SSCP method followed by sequencing in order to assess the genetic
      variability of coding and noncoding parts of the genome of Echinococcus
      granulosus (Cestoda; Taeniidae) and to test whether or not the parasite
      populations are mainly self-fertilizing. For this, we analysed a sample of 110 E.
      granulosus metacestode isolates collected from different geographical regions
      (Southern Brazil, Europe and Australia) and from different intermediate hosts
      (ovine, bovine, human, macropod, swine and equine). Using appropriate controls,
      we were able to identify 4 strains in that sample (sheep, cattle, pig and horse
      strains). The high degree of genetic differentiation between strains, but not
      within, and the monomorphism found in most loci (EgAg4, EgActII, EgHbx2 and EgAg6
      non-coding-EgAgB/1 and EgND1-coding) indicated that they are largely selfed. On
      the other hand, outcrossing was also shown to occur, since 5 potential hybrid
      genotypes between cattle and sheep strains were found in populations of Southern
      Brazil, but absent in other geographical areas. We suggest that both processes
      are adaptive. The article also reports, for the first time, the occurrence of the
      E. granulosus cattle strain in South America.

PMID- 10070664
TI  - Scanning for nucleotide variations in mitochondrial DNA fragments of Schistosoma
      japonicum by single-strand conformation polymorphism.
AB  - In this study, we employed a mutation scanning approach for the direct visual
      display of genetic variability in mitochondrial DNA (mtDNA) fragments within and
      among populations of Schistosoma japonicum from the People's Republic of China.
      Fragments of the NADH dehydrogenase 1 gene (ND1) and the cytochrome c oxidase
      subunit I (COI) were individually amplified from parasite DNA by polymerase chain
      reaction (PCR), denatured and subjected to single-strand conformation
      polymorphism (SSCP) analysis. Using ND1 and COI fragments, individuals
      representing different genotypes could be readily identified based on
      characteristic and reproducible SSCP profiles. The results demonstrated the
      usefulness of SSCP for the direct visual display of low-level sequence variation
      in mtDNA of S. japonicum prior to DNA sequence analysis. This approach has
      important implications for studying the genetic structure and biology of S.
      japonicum populations, and for analysing the inheritance of mitochondrial DNA.

PMID- 10070665
TI  - Periodate-sensitive immunological cross-reactivity between keyhole limpet
      haemocyanin (KLH) and serodiagnostic Schistosoma mansoni egg antigens.
AB  - Both CEF6, a cation-exchange fraction of soluble Schistosoma mansoni egg antigens
      (SEA), composed of the 2 antigens, alpha-1 and omega-1, and haemocyanin from the
      keyhole limpet, Megathura crenulata, have shown potential for immunodiagnosis of
      human schistosomiasis. Possible cross-reactivity between antigens in SEA and
      keyhole limpet haemocyanin (KLH) was explored by Western immunoblotting and
      enzyme-linked immunosorbent assay (ELISA) using sera from rabbits immunized with
      KLH, SEA, CEF6, alpha-1, omega-1, or egg antigen k5. Both immunoassays revealed a
      high degree of serological cross-reactivity between the schistosome egg antigens
      and KLH, much of it due to sodium periodate-sensitive epitopes. Cross-reactivity
      with schistosome antigens with proven diagnostic efficacy may thus, in part,
      explain the usefulness of KLH for the diagnosis of human schistosomiasis mansoni.

PMID- 10070666
TI  - An immunohistological study of phenotypic characteristics of cells of the
      inflammatory response in the intestine of Schistosoma bovis-infected goats.
AB  - The cellular inflammatory response in the small intestine of 21 goats infected
      with Schistosoma bovis was phenotypically characterized by immunohistochemistry
      between 6 and 32 weeks post-exposure, with particular reference to perioval
      granulomatous reactions. Macrophages of granulomas consistently expressed MHC
      class II molecules, whereas multi-nucleated giant cells in general did not. Most
      granulomas contained moderate infiltrates of CD2+ (CD4+ or CD8+) and gamma/delta
      (T19+) T cells, whereas B lymphocytes were sparse. Intact extravascular mucosal
      eggs, lacking appreciable cellular reactivity on plain histopathology, displayed
      surrounding collars of MHC class II+ macrophages. Gamma/delta T cells and MHC
      class II+ macrophages were the predominant cell types in perivascular
      inflammatory cell clusters in the submucosa. The phenotypic cellular composition
      of granulomas did not change appreciably with duration of infection. The results
      indicate the importance of MHC class II-restricted immune events in the caprine
      S. bovis egg granulomas and also suggest a role of gamma/delta T cells in their
      pathogenesis. It is hypothesized that the early appearance of perioval macrophage
      collars may serve to protect eggs from ovicidal host defence mechanisms,
      facilitating excretion and continuation of the life-cycle.

PMID- 10070667
TI  - Adult resistance to schistosomiasis mansoni: age-dependence of reinfection
      remains constant in communities with diverse exposure patterns.
AB  - In a fishing community on Lake Albert in Uganda the pattern of intensity of
      Schistosoma mansoni infection 6 months after treatment with praziquantel was
      found to be very similar to reinfection patterns seen in previously studied
      endemic communities: the profile peaks sharply at around the age of 10 years
      falling away rapidly to much lower levels in adults. This is in stark contrast to
      the patterns of water contact, which differ greatly between fishing and non
      fishing communities. On Lake Albert, adults appear to be more heavily exposed
      than children. From these observations we conclude that adults are
      physiologically (perhaps immunologically) more resistant to infection after
      treatment than children.

PMID- 10070668
TI  - The ancient and divergent origins of the human pathogenic trypanosomes,
      Trypanosoma brucei and T. cruzi.
AB  - This study presents new findings concerning the evolution of the human pathogens,
      Trypanosoma brucei and T. cruzi, which suggest that these parasites have
      divergent origins and fundamentally different patterns of evolution. Phylogenetic
      analysis of 18S rRNA sequences places T. brucei in a clade comprising exclusively
      mammalian trypanosomes of African origin, suggesting an evolutionary history
      confined to Africa. T. cruzi (from humans and sylvatic mammals) clusters with
      trypanosomes specific to Old and New World bats, T. rangeli and a trypanosome
      species isolated from an Australian kangaroo. The origins of parasites within
      this clade, other than some of those from bats, lie in South America and
      Australia suggesting an ancient southern super-continent origin for T. cruzi,
      possibly in marsupials; the only trypanosomes from this clade to have spread to
      the Old World are those infecting bats, doubtless by virtue of the mobility of
      their hosts. Viewed in the context of palaeogeographical evidence, the results
      date the divergence of T. brucei and T. cruzi to the mid-Cretaceous, around 100
      million years before present, following the separation of Africa, South America
      and Euramerica. The inclusion in this study of a broad range of trypanosome
      species from various different hosts has allowed long phylogenetic branches to be
      resolved, overcoming the limitations of many previous studies. Moreover, T.
      brucei and the other mammalian tsetse-transmitted trypanosomes appear, from these
      data, to be evolving several times faster than T. cruzi and its relatives.

PMID- 10070669
TI  - Parasite-induced anorexia: leptin, insulin and corticosterone responses to
      infection with the nematode, Nippostrongylus brasiliensis.
AB  - The nematode parasite, Nippostrongylus brasiliensis, induces a biphasic anorexia
      in its rat host. The mechanisms, underlying this anorexia and its possible
      advantages to the host or parasite are unknown. We have investigated the effect
      of acute (12-24 h) and chronic (2-17 days) infections on plasma concentrations of
      leptin, insulin and corticosterone, and on hypothalamic expression of
      neuropeptide Y, galanin and corticotrophin-releasing factor genes. Plasma leptin
      was elevated in infected rats relative to uninfected ad libitum-fed controls and
      pair-fed controls in 12 h infections initiated at dark onset and in infections of
      2 days' duration. At other times prior to parasite expulsion, plasma leptin in
      infected and pair-fed rats was lower than that of uninfected ad libitum-fed
      controls, reflecting the existing state of negative energy balance. Elevated
      plasma leptin concentrations in infected rats at day 2 post-infection were
      accompanied by reduced neuropeptide Y gene expression in the hypothalamic arcuate
      nucleus compared with both ad libitum control and pair-fed animals, and by
      lowered corticotrophin-releasing factor gene expression in the paraventricular
      nucleus relative to pair-feds. Twelve hour infections were characterized by a
      substantial increase in plasma corticosterone that was independent of reduced
      food intake, and in 12 h infections initiated at dark onset, where plasma leptin
      was elevated, there was also increased plasma insulin concentration in infected
      rats. In longer infections, differences between the groups in plasma insulin and
      corticosterone concentration were only observed at day 4 post-infection. In
      summary, perturbations to leptin, insulin and corticosterone signals early in
      infection may have a causative role and might feed back onto hypothalamic gene
      expression, whereas subsequent changes in these parameters are more likely to be
      secondary to negative energy balance.

PMID- 10070670
TI  - Redesign of trials under different enrollment mixes.
AB  - A few large multi-centre male-only heart trials done in the 1970s and 1980s have
      been seen as ill-conceived because they did not include females. The purpose here
      is to revisit two of those trials and to consider consequences in terms of cost
      and power had they been designed to include females.

PMID- 10070672
TI  - Planning group sizes in clinical trials with a continuous outcome and repeated
      measures.
AB  - Simple formulae have been derived for the accurate computation of sample sizes
      when the two-sample t-test is used. Required sample sizes may be reduced by
      taking repeated measures, especially if correlations are about equal. In a trial
      with two parallel groups, repeated measures may be summarized by a pre-treatment
      mean and a post-treatment mean. In a cross-over trial measures may be repeated
      within each treatment period. In case the difference between two independent
      groups increases in time, individual slopes may be used if the correlation
      between two measures hardly depends on distance in time between these measures.
      However, it may be more efficient to use only the first and last measure in the
      statistical test if correlations strongly depend on time distance.

PMID- 10070673
TI  - Construction of uniform-balanced cross-over designs for any odd number of
      treatments.
AB  - Cross-over designs balanced for simple carry-over effects are commonly applied in
      clinical studies for the comparison of treatments for chronic conditions such as
      hypertension or asthma. Uniform-balanced cross-over designs have the desirable
      property that the treatment sequences are arranged so that, in the full design,
      each treatment is followed by every other treatment equally often. Such designs
      for an even number of treatments and the same number of sequences and periods are
      readily constructed using suitable cyclic Latin squares. For an odd number of
      treatments, pairs of squares may be combined to give uniform-balanced designs.
      Recently, computer search techniques have been used to find nearly-balanced Latin
      squares which may be combined in pairs or in sets of three to produce designs
      with the overall properties of uniformity and balance. In this paper, simple
      generating formulae are described which will give, for any odd number of
      treatments t > 3, uniform-balanced cross-over designs with p = t periods and n =
      kt treatment sequences for any k > or = 2. Tables of cross-over designs obtained
      from these simple formulae are presented for t < or = 15.

PMID- 10070674
TI  - Comparing several score tests for interval censored data.
AB  - I create a general model to perform score tests on interval censored data.
      Special cases of this model are the score tests of Finkelstein, Sun and Fay.
      Although Sun's was derived as a test for discrete data and Finkelstein's and
      Fay's tests were derived under a grouped continuous model, by writing all tests
      under one general model we see that as long as the regularity conditions hold,
      any of these three classes of tests may be applied to either grouped continuous
      or discrete data. I show the equivalence between the weighted logrank form of the
      general test and the form with a term for each individual, the form often used
      with permutation tests. From the weighted logrank form of the tests, we see that
      Sun's and Finkelstein's test are similar, giving constant (or approximately
      constant) weights to differences in survival distributions over time. In
      contrast, the proportional odds model (Fay's model with logistic error) gives
      more weight to early differences.

PMID- 10070675
TI  - Criticism of a hierarchical model using Bayes factors.
AB  - This paper analyses a data file of heart transplant surgeries performed in the
      United States over a two-year period. A Poisson/gamma exchangeable model is used
      to learn about the underlying death rates for 94 hospitals. There are concerns
      about the suitability of this hierarchical model, including the need for a
      hierarchical structure, the existence of outliers, the choice of prior
      hyperparameters, the need for a covariate in the model, and the manner in which
      exchangeability was modelled. Each concern motivates the construction of
      alternative models and Bayes factors are used to compare the existing model with
      the alternative models. Graphical displays are used to check the sensitivity of
      the posterior analysis with respect to model perturbations and plots of Bayes
      factors are used to criticize these perturbations.

PMID- 10070676
TI  - Semi-parametric estimation of age-time specific infection incidence from serial
      prevalence data.
AB  - Many infections cause lasting detectable immune responses, whose prevalence can
      be estimated from cross-sectional surveys. However, such surveys do not provide
      direct information on the incidence of infection. We address the issue of
      estimating age and time specific incidence from a series of prevalence surveys
      under the assumption that incidence changes exponentially with time, but make no
      assumption about the age specific incidence. We show that these assumptions lead
      to a proportional hazards model and estimate its parameters using semi-parametric
      maximum likelihood methods. The method is applied to tuberculin surveys in The
      Netherlands to explore age dependence of the risk of tuberculous infection in the
      presence of a strong secular decline in this risk.

PMID- 10070677
TI  - Meta-analysis: formulating, evaluating, combining, and reporting.
AB  - Meta-analysis involves combining summary information from related but independent
      studies. The objectives of a meta-analysis include increasing power to detect an
      overall treatment effect, estimation of the degree of benefit associated with a
      particular study treatment, assessment of the amount of variability between
      studies, or identification of study characteristics associated with particularly
      effective treatments. This article presents a tutorial on meta-analysis intended
      for anyone with a mathematical statistics background. Search strategies and
      review methods of the literature are discussed. Emphasis is focused on analytic
      methods for estimation of the parameters of interest. Three modes of inference
      are discussed: maximum likelihood; restricted maximum likelihood, and Bayesian.
      Finally, software for performing inference using restricted maximum likelihood
      and fully Bayesian methods are demonstrated. Methods are illustrated using two
      examples: an evaluation of mortality from prophylactic use of lidocaine after a
      heart attack, and a comparison of length of hospital stay for stroke patients
      under two different management protocols.

PMID- 10070678
TI  - A method for deciding early stopping of inconclusive case-control studies in
      settings where data are stratified.

PMID- 10070679
TI  - An issue of statistical analysis in controlled multi-centre studies: how shall we
      weight the centres?
AB  - When analysing data from a controlled multi-centre study, an important issue is
      how to weight each centre to assess the overall treatment effect. The unweighted
      analysis, which weights all centres equally, was recommended by many
      statisticians and the U.S. Food and Drug Administration, and has been routinely
      utilized as the primary statistical method for many phase III clinical studies in
      the pharmaceutical industry. The weighted analysis, which weights centres
      relative to the number of patients in them, was considered not meaningful in the
      presence of treatment-by-centre interaction. This paper demonstrates why we
      should hesitate to use the unweighted analysis as the primary statistical method
      of a study from a statistical power perspective. It also shows that the weighted
      analysis is meaningful, even in the presence of treatment-by-centre interaction,
      and that it is generally the preferred approach.

PMID- 10070680
TI  - R2: a useful measure of model performance when predicting a dichotomous outcome.
AB  - R2 has been criticized as a measure of model performance when predicting a
      dichotomous outcome, both because its value is often low and because it is
      sensitive to the prevalence of the event of interest. The C statistic is more
      widely used to measure model performance in a 0/1 setting. We use a simple
      parametric family of models to illustrate the potential usefulness of models with
      low R2 values, to clarify the effect of prevalence on both C and R2, and to
      demonstrate how R2 captures information not picked up by C. We also show that C
      is subject to a 'random mixing' problem that does not affect R2. Finally, we
      report both R2 and C values for different risk-adjustment models in situations
      with different prevalences and show the relationship between the measures and
      decile death rates, thereby providing a context for interpreting R2 values in a
      0/1 setting.

PMID- 10070681
TI  - Latent variables, measurement error and methods for analysing longitudinal binary
      and ordinal data.
AB  - We explore structural equations with latent variables for modelling between
      individual variability and measurement error in the analysis of longitudinal
      binary and ordinal data. The structural equation formulation provides insight
      into the assumptions and differences in interpretation of methods that are
      popular for longitudinal data analysis. Introducing the concept of continuous
      latent variables makes it clear that marginal and cluster-specific models differ
      because their predicted variables are scaled to different standard deviations,
      and that adjustment for measurement error in the outcome involves a change in
      scale as well. We apply both structural equation modelling and common
      longitudinal modelling approaches to data from a study of sleep disorders. In the
      process, we compare results from marginal modelling using an SAS GEE routine
      (Karim and Zeger, 1988), Qu's GAUSS program (Qu, 1992) for generalized mixed
      models using GEE, the MIXOR package for cluster-specific mixed effects models
      (Hedeker and Gibbons, 1994), and LISCOMP for structural models (Muthen, 1988).

PMID- 10070682
TI  - The estimation of lifetime risk and average age at onset of a disease using a
      multivariate exponential hazard rate model.
AB  - Readily grasped concepts such as lifetime risk of, and expected age at onset of,
      a disease, cannot be easily estimated by the relative risk methods commonly used
      in epidemiology. Here we develop a method for estimating these quantities with
      confidence intervals, where the likelihood is a multivariate function of exposure
      variables. The model is basically non-parametric, except for a proportional
      hazards assumption on exposures, and except for the youngest data-poor ages,
      where an exponential model in age is assumed. Tests of goodness-of-fit of the
      model are described, these allowing for product terms between exposures and age.
      Application of the method is made to the Adventist Health Study cohort, where the
      independent effects of several exposures on these outcomes are demonstrated.

PMID- 10070683
TI  - Potential for bias in estimating human fecundability parameters: a comparison of
      statistical models.
AB  - Fecundability studies, where couples attempting pregnancy subject to 'failure'
      (conception) one time in each menstrual cycle, present a natural discrete failure
      time scenario. Because the biologic capacity to conceive varies among couples in
      the population, a complication arises in choosing a method of analysis, related
      to the fact that the maximum follow-up time can vary from study to study, and
      follow-up time could potentially have different effects on parameters based on
      different approaches to modelling. Traditional development in fertility studies
      has been based on an implicit assumption that binary outcomes for different
      menstrual cycles are mutually independent. We contrast traditional models to a
      random effects model where cycle viability is modelled as subject-specific. We
      clarify the interpretations for different parameters from different models. We
      show that the traditional approach yields some regression parameters that depend
      on follow-up time, limiting the generalizability of inferences based on this
      analytic approach. By contrast, the subject-specific model consistently estimates
      parameters of interest, if the underlying distribution is properly specified.
      Data from a fecundability study carried out in North Carolina serves to
      illustrate these points.

PMID- 10070684
TI  - A multivariate approach for assessing severity of acute graft-versus-host disease
      in bone marrow transplantation.
AB  - Patients undergoing bone marrow transplantation are at high risk of developing
      acute graft-versus-host disease (GVHD) which is a primary limiting factor for
      this procedure inasmuch as it is responsible for high morbidity rates and is
      associated with poor survival outcome. To provide improved treatment assessment
      and better interpretation of clinical outcomes, we need a precise and objective
      assessment of GVHD. Severity of GVHD is commonly assessed using an imprecise
      categorical grading system that incorporates skin, gut and liver grades, as well
      as subjective assessment of clinical performance. These organ grades are based on
      arbitrary cutpoints of skin rash, diarrhoea volume and bilirubin level. The
      International Bone Marrow Transplant Registry proposed an alternative grading
      system based on different combinations of organ involvement and provided
      estimates of relative risk of treatment failure. On the basis of that work, we
      developed an empirical mathematical model that quantifies GVHD severity, and that
      uses continuous, rather than categorical, daily measurements for each organ
      system. We use model-predicted values as an index of severity for any combination
      of values. The proposed index allows a more precise comparison of GVHD profiles
      across different treatment protocols and also permits more refined analyses to
      address relationships between GVHD and clinical outcomes.

PMID- 10070686
TI  - Probabilistic analysis of global performances of diagnostic tests: interpreting
      the Lorenz curve-based summary measures.
AB  - Several indices based on the receiver operating characteristic curve (ROC curve)
      have previously been found to possess probabilistic interpretations. However,
      these interpretations are based on some unrealistic diagnostic scenarios. In this
      paper, the author presents a new approach using the Lorenz curve. The author
      found that the summary indices of the Lorenz curve, that is, the Pietra index and
      the Gini index, can be interpreted in several ways ('average change in post-test
      probability', 'per cent maximum prognostic information', and 'probability of
      correct diagnosis'). These interpretations have a close tie with real-world
      medical diagnosis, suggesting that these indices are proper measures of test
      characteristics.

PMID- 10070685
TI  - Mixture models for cancer survival analysis: application to population-based data
      with covariates.
AB  - The interest in estimating the probability of cure has been increasing in cancer
      survival analysis as the curability of many cancer diseases is becoming a
      reality. Mixture survival models provide a way of modelling time to death when
      cure is possible, simultaneously estimating death hazard of fatal cases and the
      proportion of cured case. In this paper we propose an application of a parametric
      mixture model to relative survival rates of colon cancer patients from the
      Finnish population-based cancer registry, and including major survival
      determinants as explicative covariates. Disentangling survival into two different
      components greatly facilitates the analysis and the interpretation of the role of
      prognostic factors on survival patterns. For example, age plays a different role
      in determining, from one side, the probability of cure, and, from the other side,
      the life expectancy of fatal cases. The results support the hypothesis that
      observed survival trends are really due to a real prognostic gain for more
      recently diagnosed patients.

PMID- 10070687
TI  - Using missing data methods in genetic studies with missing mutation status.
AB  - Because of current techniques of determining gene mutation, investigators are now
      interested in estimating the odds ratio between genetic status (mutation, no
      mutation) and an outcome variable such as disease cell type (A, B). In this paper
      we consider the mutation of the RAS genetic family. To determine if the genes
      have mutated, investigators look at five specific locations on the RAS gene. RAS
      mutated is a mutation in at least one of the five gene locations and RAS non
      mutated is no mutation in any of the five locations. Owing to limited time and
      financial resources, one cannot obtain a complete genetic evaluation of all five
      locations on the gene for all patients. We propose the use of maximum likelihood
      (ML) with a 2(6) multinomial distribution formed by cross-classifying the binary
      mutation status at five locations by binary disease cell type. This ML method
      includes all patients regardless of completeness of data, treats the locations
      not evaluated as missing data, and uses the EM algorithm to estimate the odds
      ratio between genetic mutation status and the disease type. We compare the ML
      method to complete case estimates, and a method used by clinical investigators,
      which excludes patients with data on less than five locations who have no
      mutations on these sites.

PMID- 10070688
TI  - Statistics in the medical literature: 3.

PMID- 10070689
TI  - Methicillin-resistant Staphylococcus aureus infections in 11 dogs.
AB  - Methicillin-resistant Staphylococcus aureus infection was identified in 11 dogs.
      The infection was associated with surgical treatment especially orthopaedic
      surgery. Infection after traumatic wounding, and recurrent pyoderma was also
      seen. Oral antibiotic treatment improved or resolved the infection in nine of the
      11 dogs, although the methicillin-resistant isolates were susceptible to
      relatively few antibiotics.

PMID- 10070691
TI  - Pathological changes in the myocardium of hypocalcaemic parturient cows.
AB  - Three parturient cows in lateral recumbency which were moaning and had
      tachycardia, arrhythmia and dyspnoea were thoroughly examined. They were
      hypocalcaemic (0.70-1.27 mmol/litre) and were euthanized within four days,
      because they failed to respond to calcium treatment. By light microscopy the most
      characteristic pathological changes in the heart were necrotic changes scattered
      throughout the myocardium. Electron microscopy revealed abnormalities in the
      myocytes which were characterised by focal myofibrillar lysis, irregular
      splitting, streaming and spreading of the Z band and myofibrillar disarray.

PMID- 10070690
TI  - Comparison of the effects of oral or subcutaneous carprofen or ketoprofen in rats
      undergoing laparotomy.
AB  - Rats undergoing laparotomy received either carprofen (5 mg/kg) or ketoprofen (5
      mg/kg) administered orally in flavoured gelatin, or by subcutaneous injection. A
      control group that received no analgesic showed a significant (3 per cent) fall
      in bodyweight (P = 0.009) after laparotomy. This decrease was greater than that
      seen in the groups receiving carprofen (P = 0.006) or ketoprofen (P = 0.012)
      administered subcutaneously, which continued to gain weight following surgery.
      All animals showed a significant fall in food consumption but this decrease was
      greater in the jelly alone group (47 per cent) than in the group receiving
      carprofen (17 per cent) (P = 0.015) administered subcutaneously. A significant
      fall in water consumption occurred in the control group (40 per cent) and in
      animals that received oral carprofen (13 per cent) or Ketoprofen (22 per cent).
      No significant decrease was seen in groups receiving either carprofen or
      ketoprofen administered subcutaneously (P > 0.1). This study shows that a
      relatively simple surgical procedure results in a major reduction in food and
      water consumption in rats. This reduction can be minimised by the administration
      of ketoprofen or carprofen (5 mg/kg subcutaneously), but higher dose rates are
      required if these drugs are to be administered by the oral route.

PMID- 10070692
TI  - Postanaesthetic recumbency in a Belgian filly with polysaccharide storage
      myopathy.

PMID- 10070693
TI  - Postmortem findings in a finless porpoise (Neophocaena phocaenoides) calf
      stranded in Hong Kong.

PMID- 10070694
TI  - Intestinal adenocarcinoma in sheep in Spain.

PMID- 10070695
TI  - EU ban on four antibiotic feed additives.

PMID- 10070697
TI  - Private TB testing.

PMID- 10070698
TI  - Dispensing medicines.

PMID- 10070696
TI  - Antibiotic-resistant Salmonella in pigs in Spain.

PMID- 10070699
TI  - Level and duration of serum antibodies in cattle infected experimentally and
      naturally with bovine virus diarrhoea virus.
AB  - Neutralising serum antibodies against bovine virus diarrhoea virus (BVDV) were
      monitored for three years in 35 cattle that were infected with the virus as
      calves; 24 of the calves were inoculated intramuscularly or intranasally, and 11
      contracted the infection naturally. All the experimentally infected calves
      seroconverted within 14 to 28 days after inoculation, and all the animals still
      had high serum levels of antibodies to BVDV three years after infection.
      Determinations of antibody levels in milk and blood samples excluded the
      possibility that the calves had been reinfected with BVDV during the study.

PMID- 10070700
TI  - Adaptation of dogs to the amputation of a limb and their owners' satisfaction
      with the procedure.
AB  - Forty-four Dutch dog owners were interviewed by telephone about their experiences
      with their dog after it had had a limb amputated. Most of the dogs adapted to
      walking on three legs within a month, sooner than most of the owners had
      expected. There were few complications after the amputation, although changes in
      behaviour were observed in approximately one-third of the dogs.

PMID- 10070701
TI  - Feline infectious peritonitis presenting as a tumour in the abdominal cavity.
AB  - This paper describes six cases of feline infectious peritonitis (FIP) in which an
      abdominal tumour had been suspected clinically. Pathological changes were mainly
      restricted to the massive enlargement of a mesenteric lymph node due to
      necrogranulomatous lymphadenitis. FIP was diagnosed on the basis of the
      immunohistological demonstration of coronavirus antigen in intact macrophages
      within the necrogranulomatous lesions. In the affected lymph node lymphoid tissue
      was either almost completely effaced or restricted to follicles composed mainly
      of variable numbers of blasts. From one to many plasma cells positive for
      coronavirus-specific antibodies were present in the marginal sinuses or capsules.
      In addition, necrogranulomas were present in the gut-associated lymphoid tissue
      of the caecum of one cat, and adjacent to the affected lymph node of another.

PMID- 10070702
TI  - Ultrasonographic findings in three cows with chronic ragwort (Senecio alpinus)
      poisoning.
AB  - Three cows with regwort (Senecio alpinus) poisoning were examined clinically,
      haematologically and ultrasonographically, and biopsy specimens of the liver were
      examined histologically. At the end of the study, the cows were euthanased and
      examined postmortem. The major clinical signs included severely disturbed general
      demeanour and behaviour, and severe diarrhoea. One cow was photosensitive. The
      activities of liver enzymes and the concentration of bilirubin were high in all
      of the cows. In two of the cows, ultrasonographic examination revealed a heavy
      accumulation of abdominal fluid, which was diagnosed as non-inflammatory ascites.
      In all the cows, the liver parenchyma was heterogeneous, and cows 1 and 2 had
      multiple echogenic foci 5 to 10 mm in diameter. In cow 3, the facies
      diaphragmatica of the liver appeared irregular in outline owing to the presence
      of nodules which were approximately 5 cm in diameter. The liver was also greatly
      enlarged and extended almost to the linea alba ventrally and beyond the reticulum
      cranially. All the cows had portal hypertension and the portal vein was dilated,
      resulting in oedema of the walls of the gall bladder, the small intestines and
      the omentum. The diameter of the caudal vena cava was reduced as a result of the
      impaired hepatic circulation. Histological examination of liver biopsy specimens
      revealed severe hepatic fibrosis in all the cows.

PMID- 10070703
TI  - Encephalitis related to Chlamydia psittaci infection in a 14-week-old calf.

PMID- 10070704
TI  - Comparative in vitro activity of valnemulin against porcine bacterial pathogens.

PMID- 10070705
TI  - Veterinary education: time to abandon the cult of coverage.

PMID- 10070706
TI  - Arrangements for the training of veterinary nurses.

PMID- 10070707
TI  - Arrangements for the training of veterinary nurses.

PMID- 10070708
TI  - Updating the Veterinary Surgeons Act.

PMID- 10070709
TI  - Radiocaesium and radiostrontium uptake by turnips and broad beans via leaf and
      root absorption.
AB  - One of the immediate consequences of massive radioisotope release into the
      atmosphere is contamination of the biosphere. This contamination can affect
      plants either by direct deposition onto the leaves, or by contaminating the soil
      followed by absorption by the roots. Knowledge of the efficacy of the two routes
      of radionuclide incorporation into the food chain is fundamental to understanding
      the mechanisms by which radioactive contamination reaches man. The present work
      analyzes the incorporation of 134Cs and 85Sr via root and leaf uptake into the
      parts consumed by man, for two very different crops: turnip (Brassica napus) and
      broad bean (Vicia faba). The root uptake studies consider the available soil
      fraction for these two radionuclides, and indicate greater availability for 85Sr
      than for 134Cs which is fixed rapidly in the soil. For the study of leaf uptake,
      leaves were contaminated at three different stages of plant growth; the results
      indicate an inverse dependence of the transfer coefficients on the time elapsed
      from the moment of the contamination to harvesting of the edible parts.

PMID- 10070710
TI  - Platelet labeling with 67Ga chelates.
AB  - 68Ga-labeled platelets could be useful for positron emission tomographic (PET)
      studies. In order to identify the optimal chelate for radiolabeling of platelets
      with 68Ga, we investigated the platelet uptake of 67Ga-oxine, -tropolone and 
      MPO. The platelet uptake of 67Ga-oxine and -tropolone is very low (< 5%). The
      platelet uptake of 67Ga-MPO, in contrast, increases with platelet density
      (highest at 10(9) platelets/ml) up to 18%. Our data provide evidence that only
      68Ga-MPO could be useful for PET-studies.

PMID- 10070711
TI  - A trial study of leukocyte labeling with stabilized Tc-99m D,L-HMPAO by methylene
      blue and sodium phosphate buffer.
AB  - We attempted to label leukocytes with stabilized Tc-99m D,L-HMPAO by methylene
      blue and sodium phosphate buffer (S-HMPAO). METHODS: The results were compared
      with unstabilized Tc-99m D,L-HMPAO (U-HMPAO). U-HMPAO was obtained by
      reconstituting a commercial vial of D,L-HMPAO. Stabilization of the kit was
      performed by the addition of methylene blue. The leukocytes were labeled using a
      modified published method. The test samples of S-HMPAO and U-HMPAO were prepared
      immediately, and stood for 0.5, 1, 2, 4, and 6 h, respectively, at room
      temperature before analysis. RESULTS: In comparison with U-HMPAO: (1) the
      radiochemical purity of S-HMPAO was higher; (2) the labeling efficiencies of S
      HMPAO labeled leukocytes were higher and consistent; (3) the viability of S-HMPAO
      labeled leukocytes was as high as the viability of U-HMPAO labeled leukocytes at
      any time; and (4) the percentages of disintegrated from S-HMPAO labeled
      leukocytes in plasma were lower. CONCLUSION: S-HMPAO is more stable than U-HMPAO
      and can provide higher leukocyte labeling efficiency. S-HMPAO, therefore, has the
      potential to replace U-HMPAO as a leukocyte-labeling agent.

PMID- 10070712
TI  - Synthesis and autoradiographic localization of muscarinic cholinergic antagonist
      (+)N-[11C]methyl-3-piperidyl benzilate as a potent radioligand for positron
      emission tomography.
AB  - (+)N-[11C]methyl-3-piperidyl benzilate, a relatively low affinity muscarinic
      cholinergic receptor antagonist was synthesized by N-[11C]methylation of (+)3
      piperidyl benzilate using [11C]methyl iodide. The product was isolated by HPLC,
      and obtained with radiochemical yield of 60-70% from [11C]methyl iodide, and a
      specific activity of 500-1000 Ci mmol-1 (18.5-37 GBq mumol-1) at EOS and
      radiochemical purity of > 98%. In vitro autoradiographic studies showed selective
      binding for this radiotracer in the different regions of the rat brain: high in
      corpus striatum, hippocampus and cerebral cortex, and low in cerebellum,
      consistent with muscarinic cholinergic receptor distributions. This radiotracer
      thus had potential as radioligand for positron emission tomography.

PMID- 10070713
TI  - Automated synthesis of [11C]choline, a positron-emitting tracer for tumor
      imaging.
AB  - (beta-Hydroxyethyl)tri([11C]methyl)ammonium ([11C]choline) is a tracer very
      effective in imaging various human tumors using positron emission tomography
      (PET). We have constructed a computer-controlled [11C]choline synthetic apparatus
      which carries out the whole process of synthesis and product purification
      automatically. The setup is simple and the process quick. In 20 min, 11 GBq of
      [11C]choline (chloride) is obtainable from 26 GBq of [11C]CO2. The final product
      is a sterile and pyrogen-free [11C]choline "injection".

PMID- 10070714
TI  - Use of EPR spin probe technique for detection of irradiated wheat.

PMID- 10070715
TI  - Relationships between ESR-evaluated doses estimated from enamel and activity of
      radionuclides in bone and teeth of reindeer.
AB  - Doses of radiation estimated from ESR analysis of tooth enamel were compared with
      activities of alpha- and beta-emitters in enamel and in bone tissue of mandibles
      of 77 reindeer from populations with different levels of radiation contamination.
      Contribution of the radionuclides incorporated into bone (or bone-seeking
      radionuclides in food) to ESR-evaluated doses was substantial and the
      contribution of the radionuclides incorporated into enamel itself proved to be
      relatively small.

PMID- 10070716
TI  - Reproducibility study of TLD-100 micro-cubes at radiotherapy dose level.
AB  - The precision of the thermoluminescent response of Harshaw micro-cube dosimeters
      (TLD-100), evaluated in both Harshaw thermoluminescent readers 5500 and 3500, for
      1 Gy dose value, was investigated. The mean reproducibility for micro-cubes, pre
      readout annealed at 100 degrees C for 15 min, evaluated with the manual planchet
      reader 3500, is 0.61% (1 standard deviation). When micro-cubes are evaluated with
      the automated hot-gas reader 5500, reproducibility values are undoubtedly worse,
      mean reproducibility for numerically stabilised dosimeters being equal to 3.27%
      (1 standard deviation). These results indicate that the reader model 5500, or, at
      least, the instrument used for the present measurements, is not adequate for
      micro-cube evaluation, if precise and accurate dosimetry is required. The
      difference in precision is apparently due to geometry inconsistencies in the
      orientation of the imperfect micro-cube faces during readout, requiring careful
      and manual reproducible arrangement of the selected micro-cube faces in contact
      with the manual reader planchet.

PMID- 10070717
TI  - Groundwater flow system in the valley of Toluca, Mexico: an assay of natural
      radionuclide specific activities.
AB  - Natural radionuclides and physicochemical parameters have been evaluated in
      groundwater samples from boreholes belonging to the drinking water supply system
      of the Toluca City, Mexico. The results obtained for radon and radium, together
      with the physicochemical parameters of the studied samples, indicate a fast and
      efficient recharge pattern. The presence of a local and a regional groundwater
      flows was also observed. The local flow belongs to shallower water, recognized by
      its low radon content and dissolved ions, as compared with the regional, deeper
      groundwater flow with a longer residence time.

PMID- 10070718
TI  - Terrestrial gamma ray dose rates of Brunei Darussalam.
AB  - GPS-indexed in-situ and car-borne survey of terrestrial gamma-ray dose rates were
      carried out in Brunei and adjacent areas using two portable NaI(Tl) counters. The
      mean and population weighted average dose rates for Brunei are 34 and 33 nGy/h,
      respectively. The car-borne data and the in-situ data when spectral analysed
      separately, were found to show fractal behaviour with D of 1.7 and 1.8,
      respectively. A contour map of the dose rates was also produced.

PMID- 10070720
TI  - Inefficiency of Mycobacterium chlorophenolicum PCP-1 to enhance mineralization of
      pentachlorophenol in soil microcosms.
AB  - We examined the mineralization of pentachlorophenol (PCP) in sterile and non
      sterile soil with or without added bacteria (Mycobacterium chlorophenolicum PCP
      1). The soil used had no history of PCP contamination. Microcosms (30 g dry
      weight of soil) were incubated with labelled PCP (6.76% 13C, a non-radioactive
      stable isotope, 22 mg kg-1 dry weight) for 60 days. M. chlorophenolicum PCP-1
      (7.8 x 10(6) cells g-1 dry weight) was added to some samples. 50% of the PCP was
      mineralized in non-sterile soil with or without the exogenous bacteria. Only 5%
      of the PCP was mineralized in sterile soil with or without bacteria. These data
      suggest that the PCP was not accessible to M. chlorophenolicum and that the
      indigenous soil microflora can mineralize PCP.

PMID- 10070721
TI  - Characterization of genes for enzymes involved in the phenanthrene degradation in
      Nocardioides sp. KP7.
AB  - The nucleotide sequence of the gene cluster, phdEFABGHCD, encoding enzymes
      responsible for the transformation of phenanthrene to 1-hydroxy-2-naphthoate in
      Nocardioides sp. strain KP7 was determined. This gene cluster, which may
      constitute a single operon, resided at 6.1-kb downstream of the phdIJK gene
      cluster encoding the enzymes for the transformation of 1-hydroxy-2-naphthoate to
      o-phthalate. In general, the phd products exhibited moderate degrees of homology
      with isofunctional enzymes found in pathways for the degradation of other
      aromatic compounds. Remarkably, the phdC gene product had features of the [3Fe
      4S] type ferredoxin, which has not been found so far as a component of the ring
      hydroxylating dioxygenase. Escherichia coli carrying the genes for phenanthrene
      dioxygenase, phdABCD, was capable to oxidize phenanthrene.

PMID- 10070722
TI  - Laboratory simulation of biodegradation of chemicals in surface waters: closed
      bottle and respirometric test.
AB  - Microbial degradation is the most dominant elimination mechanism of organics from
      the environment. For evaluation of biodegradability of pure chemicals many
      standardized tests are available, but no standardized procedure for assessment of
      biodegradability of chemicals in surface water is agreed upon. Rates of in-situ
      biodegradation are usually estimated in laboratory simulation where environmental
      factors are reproduced to some extent. The aim of our study was to compare
      standardised ready biodegradability assessment, test (Closed bottle test) and its
      modifications employing the basic agreements on test conditions to simulate
      biodegradation in surface water. Standard test was modified using various natural
      river waters to simulate the natural environment in a simplified way. The impact
      of different types and amounts of nutrients and microorganisms on biodegradation
      was confirmed. The conditions in the recipient should be examined to extrapolate
      the results from ready biodegradability tests to real surface water.

PMID- 10070723
TI  - Biodegradation and toxicity of wastewater from industry producing mineral fibres
      for thermal insulation.
AB  - The water chemistry, toxicity, and biodegradation of wastewater from an industry
      producing mineral fibres for thermal insulation were studied. Values for COD,
      BOD5, suspended solids, and phenol exceeded permissible values for the wastewater
      discharged into a nearby river and acute toxicity was also detected.
      Consequently, the effluent should be treated in a municipal wastewater treatment
      plant so its ready biodegradability was investigated. We found that the
      wastewater was readily biodegradable, therefore we assume it can be treated in
      the wastewater treatment plant as the ratio of the wastewater flow rate and the
      minimal total inflow into the sewage treatment plant would be one to at least 30.

PMID- 10070727
TI  - A kinetic distribution model of evaporation, biosorption and biodegradation of
      polychlorinated biphenyls (PCBs) in the suspension of Pseudomonas stutzeri.
AB  - Kinetics of distribution of PCBs in an active bacterial suspension of Pseudomonas
      stutzeri was studied by monitoring the evaporated amounts and the concentration
      remaining in the liquid medium with the biomass. To determine the biodegradation
      rate constants of the individual congeners of the PCB formulation Delor 103, a
      model considering biosorption, evaporation, and primary biodegradation
      constructed previously was used. Rate constants of biodegradation imply that
      biodegradation of individual congeners is structure-dependent process.
      Biodegradability decreases with increasing number of chlorine substituents in the
      molecule, especially if they are in the ortho and para positions. On the other
      hand, the increasing number of free ortho and meta positions in the biphenyl
      molecule leads to better biodegradability. For a simple empirical determination
      of the influence of the chlorine substitution pattern on biodegradability, the di
      and trichlorobiphenyl rate constants of biodegradation were analysed.

PMID- 10070728
TI  - Simulation of herbicide degradation in different soils by use of Pedo-transfer
      functions (PTF) and non-linear kinetics.
AB  - The degradation behaviour of bentazone in 14 different soils was examined at
      constant temperature and moisture conditions. Two soils were examined at
      different temperatures. On the basis of these data the influence of soil
      properties and temperature on degradation was assessed and modelled. Pedo
      transfer functions (PTF) in combination with a linear and a non-linear model were
      found suitable to describe the bentazone degradation in the laboratory as related
      to soil properties. The linear PTF can be combined with a rate related to the
      temperature to account for both soil property and temperature influence at the
      same time.

PMID- 10070729
TI  - Evaluation and application of models for the prediction of ready biodegradability
      in the MITI-I test.
AB  - Three existing models and one newly developed model for the prediction of ready
      biodegradability of organic compounds are evaluated by comparing the descriptors
      they use, and the consistency of the models when applied to the set of High
      Production Volume Chemicals (HPVC) in the European Union. Linear regression
      models developed for the OECD showed the best performance in the external
      validation (84.7% correct), although comparison with the other three models is
      flawed because of the class specificity of these models. With these models 567 of
      the 894 compounds could be predicted in the validation. The multivariate
      statistical model showed the best performance in the external validation (82.7%
      correct) combined with the broadest applicability of the model. The evaluation of
      the predictions of the models for the HPVC shows that all models are highly
      consistent in their prediction of not-ready biodegradability, but much less
      consistency is seen in the prediction of ready biodegradability. This complies
      with the observation that all 4 models show better performance in their
      predictions of not-ready biodegradability.

PMID- 10070730
TI  - Fate of products of degradation processes: consequences for climatic change.
AB  - The end products of atmospheric degradation are not only CO2 and H2O but also
      sulfate and nitrate depending on the chemical composition of the substances which
      are subject to degradation processes. Atmospheric degradation has thus a direct
      influence on the radiative balance of the earth not only due to formation of
      greenhouse gases but also of aerosols. Aerosols of a diameter of 0.1 to 2
      micrometer, reflect short wave sunlight very efficiently leading to a radiative
      forcing which is estimated to be about -0.8 watt per m2 by IPCC. Aerosols also
      influence the radiative balance by way of cloud formation. If more aerosols are
      present, clouds are formed with more and smaller droplets and these clouds have a
      higher albedo and are more stable compared to clouds with larger droplets. Not
      only sulfate, but also nitrate and polar organic compounds, formed as
      intermediates in degradation processes, contribute to this direct and indirect
      aerosol effect. Estimates for the Netherlands indicate a direct effect of -4 watt
      m-2 and an indirect effect of as large as -5 watt m-2. About one third is caused
      by sulfates, one third by nitrates and last third by polar organic compounds.
      This large radiative forcing is obviously non-uniform and depends on local
      conditions.

PMID- 10070731
TI  - Methane emission from lakes.
AB  - A physico-chemical model to describe methane and carbon dioxide emission from
      lakes was developed. The model describes the emission by diffusion, bubbles and
      plants. The intensity of the fluxes can be calculated either for total or
      particular emission in dependence on gas bubbles composition. It was found, that
      diffusional (Q) and bubble (J) fluxes depend on the methane molar ratio (X) in
      bubbles as follows: [formula: see text]. The model allows to estimate the role of
      the methane oxidation by atmospheric oxygen in the total methane flux. It was
      shown, that the methane oxidation does not influence much methane fluxes to the
      atmosphere for most of the experimentally observed situations.

PMID- 10070732
TI  - Degradation of polydimethylsiloxane fluids in the environment--a review.
AB  - Due to their insolubility in water and high adsorption coefficient, liquid
      polydimethylsiloxanes (PDMS) discharged as effluent will adsorb to particulate
      matter and, therefore, will become a component of sewage sludge during waste
      water treatment. The subsequent environmental fate of PDMS will depend on the
      fate of the sludge. Due to increasing practices of soil amendment with sewage
      sludge the principal environmental compartment receiving PDMS fluids is the soil.
      Degradation of PDMS is a common process taking place in many different types of
      soils. It occurs through a unique combination of environmental degradation
      processes. Initial hydrolysis of PDMS is catalysed by clay minerals, the
      principal component of soil. The primary hydrolysis product, dimethylsilanediol
      (DMSD), is then either biodegraded, or evaporated into the atmosphere, where it
      is subsequently oxidised in the presence of sunlight. The end products in both
      cases are expected to be CO2, SiO2 and H2O.

PMID- 10070733
TI  - Distribution of Pb, V, Cr, Ni, Cd, Cu and Fe in particles formed from the
      combustion of waste oils.
AB  - The determination of Pb, V, Cr, Ni, Cd, Cu and Fe in particles of different size
      obtained from the combustion of waste oils has been carried out. The study
      consists of the separation of several fractions according to the size of
      particles, the wet digestion and the individual analysis by graphite furnace
      atomic absorption spectrometry of the mentioned metals. Taking into account the
      volatilization temperature of different compounds containing the metals and their
      distribution on the size fractions, the mineral speciation of metals is proposed.

PMID- 10070734
TI  - A study on organotin levels in Canadian drinking water distributed through PVC
      pipes.
AB  - A study on organotin compounds in Canadian drinking water was carried out in
      winter-spring 1996 (28 sites) and autumn 1996 (21 sites). Approximately 29% and
      40% of distribution waters supplied through PVC pipes installed recently
      (typically less than 6 months) contained organotin compounds in the winter-spring
      and autumn surveys respectively. Monomethyl-, dimethyl-, monobutyl- and
      dibutyltin levels ranged up to 291 ng Sn/L, 49.1 ng Sn/L, 28.5 ng Sn/L and 52.3
      ng Sn/L, respectively. An additional study in summer 1996, of locations where the
      highest organotin levels were detected in the winter-spring survey, indicated
      that organotin levels had decreased in most distribution water samples. Samples
      of PVC pipe/tubing contained organotin compounds consistent with the organotin
      patterns found in the distribution water samples.

PMID- 10070735
TI  - Heterogeneous photocatalytic oxidation of organics for air purification by near
      UV irradiated titanium dioxide.
AB  - The photocatalytic degradation of high concentrations of various organic
      pollutants (acetone, 2-propanol and toluene) in dry and humid air streams was
      carried out using a specially designed photoreactor based on the UV-TiO2
      principle. The influence of several parameters which control the destruction
      efficiency (flow rate, initial contaminant and water vapour concentration,
      temperature and light intensity) has been studied. The conversion was maximal at
      room temperature, low flow rates and low initial contaminant concentrations. The
      presence of water in the inlet stream strongly affected the performance of the
      catalyst. The primary oxidation product of 2-propanol was acetone.

PMID- 10070736
TI  - Photocatalytic degradation of 5-nitro-1,2,4-triazol-3-one NTO in aqueous
      suspension of TiO2. Comparison with Fenton oxidation.
AB  - 5-nitro-1,2,4-triazol-3-one (NTO) is a powerful insensitive explosive, present in
      industrial waste waters. A remediation method based on photochemical
      decomposition and Fenton oxidation of NTO has been evaluated by monitoring the
      mineralization of 14C-labelled NTO. The TiO2-catalyzed photodegradation (lambda >
      290 nm, TiO2 0.4 g/l, NTO 150 mg/l)) leads to the complete mineralization of NTO
      in 3 hours. This degradation involves a simultaneous denitrification and ring
      scission of NTO leading to nitrites, nitrates and carbon dioxide. No significant
      photo-degradation of NTO was detected in the absence of the catalyst. Long term
      irradiation over one week, leads to a complete degradation of concentrated NTO (5
      g/l), suggesting that this method could be useful to clean-up NTO wastes. Fenton
      oxidation offers an efficient cost-effective method for NTO remediation. This
      reaction is faster that the TiO2 catalyzed photolysis and find application on the
      mineralization of high concentrations of NTO (15 g/l). Fenton oxidation provokes
      ring cleavage and subsequent elimination of the two carbon atoms of NTO as CO2.
      During this reaction, the nitro group is completely transformed into nitrates.

PMID- 10070737
TI  - Tetrahymena pyriformis: a tool for toxicological studies. A review.
AB  - Among protozoa, Tetrahymena pyriformis is the most commonly ciliated model used
      for laboratory research. After a brief description of the morphology and biology
      of Tetrahymena pyriformis, this article focuses on the most important and recent
      investigations performed with this species in toxicology and ecotoxicology. The
      methodological features of its culture, and main tests, based on cell growth
      rate, biochemical markers, behavioral changes and motility, are discussed.
      Examples of xenobiotics (organic and inorganic substances, pharmaceutical drugs,
      water pollutants) tested with Tetrahymena pyriformis are also given.

PMID- 10070738
TI  - Surface contamination with PASH, PAH and PCDD/F after fire accidents in private
      residences.
AB  - Surface samples were taken from two private residences after real fire accidents.
      The goal was, to determine the surface contaminations with polycyclic aromatic
      sulfur heterocycles (PASH), as representatives of a substance class, not
      investigated in this context, by now, polycyclic aromatic hydrocarbons (PAH) and
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F). Analytical method
      for the determination of PASH was developed for the respective matrix.
      Concentrations measured ranged between 1.70 and 465 micrograms/m2 for PASH, 34.3
      and 58,800 micrograms/m2 for PAH (EPA), and 4.15 and 1,300 ng/m2 for PCDD/F, as
      well. Obviously, PASH were formed during the fire accidents. Nevertheless, PAH
      were the most relevant pollutants after these small fires.

PMID- 10070739
TI  - An atypical iron-responsive element (IRE) within crayfish ferritin mRNA and an
      iron regulatory protein 1 (IRP1)-like protein from crayfish hepatopancreas.
AB  - A putative crayfish iron-responsive element (IRE) is present in the 5'
      untranslated region of the crayfish ferritin mRNA. The putative crayfish IRE is
      in a cap-proximal position and shares most of the structural features of the
      consensus IRE, but the RNA stem-loop structure contains a bulge of a guanine
      instead of a cytosine at the expected position, so far thought to be a hallmark
      of IREs. By using an electromobility shift assay this IRE was shown to
      specifically bind purified recombinant human iron regulatory protein 1 (IRP1) as
      well as a factor(s) present in a homogenate of crayfish hepatopancreas, likely to
      be a crayfish IRP1 homologue. With mutations in the crayfish IRE, the affinity of
      IRP to IRE was drastically decreased. A cDNA encoding an IRP1-like protein was
      cloned from the hepatopancreas of crayfish. This protein has sequence
      similarities to IRP, and contains all the active-site residues of aconitase, two
      putative RNA-binding regions and a putative contact site between RNA and IRP.
      These results show that a crayfish IRE, lacking the bulged C, can bind IRP1 in
      vitro and that an IRP1-like protein present in crayfish hepatopancreas may have
      both aconitase and RNA-binding activities.

PMID- 10070740
TI  - Biological actions of synthetic locust ion transport peptide (ITP).
AB  - Locust Ion Transport Peptide (ITP) a member of the arthropod neuropeptide family
      which includes hyperglycemic, vitellogenesis-inhibiting, and moult-inhibiting
      hormones (CHH, VIH, MIH, respectively) was synthesized as proposed by Meredith et
      al. (1996) with terminal amidation of amino acid residue 72 and with 3 disulphide
      bridges. This is the first member of this family to be synthesized. Biological
      activities of synthetic ITP (synITP) were very similar to those previously
      reported for ITP purified from Schistocerca corpora cardiaca (ScgITP) and
      partially sequenced by Audsley et al. (1992a, b). Dose-response curves for both
      synITP and ScgITP on ileal transport of Cl- (measured as increased short-circuit
      current, delta Isc), were similar with a EC50 of 1-2 nM. The Isc time course and
      maximum delta Isc across ileal epithelia at different dosages of synITP and
      ScgITP had similar patterns as did changes in transepithelial open-circuit
      potential (Vt) and resistance (Rt), reflecting changes in salt transport which
      drives fluid absorption. Disulphide bridges were shown to be required for
      biological activity of synITP, which caused the same 4-fold increase in ileal
      fluid transport rate (Jv) as previously reported for ScgITP. Both synITP and
      ScgITP caused only partial stimulation of rectal Isc and had no significant
      effect on rectal Jv. These results indicate that the structure of ITP predicted
      earlier from cDNA is correct.

PMID- 10070741
TI  - Minimum structure of peptidoglycan required for induction of antibacterial
      protein synthesis in the silkworm, Bombyx mori.
AB  - Various peptidoglycan fragments, different in mode of cross-linking and molecular
      size, were isolated, and the elicitor activity was tested for induction of
      antibacterial protein synthesis in larvae of Bombyx mori. Linear uncross-linked
      peptidoglycans from Bacillus licheniformis and Micrococcus luteus were effective
      elicitors, similar to the directly cross-linked peptidoglycan from B.
      licheniformis cell wall. The fragments of uncross-linked peptidoglycan with a
      sugar chain length of four or more were active elicitors, but the disaccharide
      unit had no elicitor activity. The minimum structure of peptidoglycan required
      for induction of antibacterial protein synthesis was determined to be two
      repeating N-acetylglucosamine-N-acetylmuramic acid units with peptide side
      chains.

PMID- 10070742
TI  - Hydrolytic enzymes of Psoroptes cuniculi (Delafond).
AB  - Phosphatases, C4 and C8 esterases, leucine and valine aminopeptidases, N-acetyl
      beta-glucosaminidase, beta-glucosidase, beta-galactosidase and beta-glucuronidase
      were detected in extracts of the parasitic mite Psoroptes cuniculi. Lipase,
      trypsin-like and chymotrypsin-like activities were not present. Haemoglobin was
      hydrolysed by a detergent-soluble fraction of the mite extracts with a maximum
      hydrolysis between pH 3 and 5. Acid proteinase activity was greater against
      haemoglobin than bovine serum albumin. Inhibitors of cysteine, serine and metallo
      proteinases failed to inhibit the hydrolysis of H-Pro-Thr-Glu-Phe-Phe(NO2)-Arg
      Leu-OH while pepstatin A inhibited its hydrolysis in a dose-dependent manner
      (IC50 8.02 x 10(-11) M (+/- 0.30 x 10(-11). Thermal inactivation of the
      proteolytic activity followed an exponential decay pattern. Typical K(m) and Vmax
      values were 7.2 x 10(-5) (+/- 0.7 x 10(-5) M-1 and 1.13 x 10(-3) (+/- 0.05 x 10(
      3) OD unit-1 min-1 respectively. Acid proteinase activity eluted from a size
      exclusion column in a single, major peak representing a molecular weight range of
      21-24.5 kDa. The major endoproteinase of P. cuniculi therefore appears to be a
      cathepsin D-like aspartic proteinase.

PMID- 10070743
TI  - Profile of the ecdysteroid hormone and its receptor in the salivary gland of the
      adult female tick, Amblyomma hebraeum.
AB  - We examined the hemolymph ecdysteroid titer (by radioimmunoassay) and profile of
      the ecdysteroid receptor (EcR/USP; by [3H]ponasterone A binding, gel mobility
      shift assay, Western blot) in the salivary gland of the ixodid tick, Amblyomma
      hebraeum Koch (Acari: Ixodidae) throughout the tick feeding period and first 6
      days post-engorgement. Throughout the slow phase of feeding, the hemolymph
      ecdysteroid titer was approximately 18 pg/microliter. The titer peaked at
      approximately 52 pg/microliter during the rapid phase of feeding, falling back to
      approximately 22 pg/microliter on the day of engorgement. Ecdysteroid titer rose
      again to approximately 750 pg/microliter by day 6 post-engorgement. EcR was
      undetectable by any of the three assays in unfed ticks. Following the onset of
      feeding, there appeared both specific ponasterone A binding and two major EcR
      bands detected by Western blot analysis. Both measurements were sustained
      throughout the feeding period, but declined after detachment when the salivary
      glands were degenerating. After ticks reached about 100 mg (by which time most
      females are mated), a discrete DNA-binding band was shown by gel mobility shift
      assay using Drosophila hsp27 EcRE as a probe. Moreover, the band intensified when
      hemolymph ecdysteroid titer reached its peak during the rapid phase of feeding;
      it declined along with decreasing EcR/USP levels, and with specific ligand
      binding activity following engorgement. This study suggests a role for the small
      hemolymph ecdysteroid peak during the rapid phase of feeding in initiating
      salivary gland degeneration.

PMID- 10070744
TI  - Molecular cloning of cAMP-dependent protein kinase catalytic subunit isoforms
      from the lone star tick, Amblyomma americanum (L.).
AB  - The salivary glands of ixodid ticks are central to tick feeding and to survival
      during off-host periods. They produce and secrete a number of molecules critical
      to maintaining the complex host-vector interface and to maintaining osmotic
      balance. We have previously shown that a cyclic AMP-dependent protein kinase
      (cAPK) is involved in the mechanism of salivary gland secretion. We have now
      cloned cDNAs encoding three isoforms of the catalytic subunit (cAPK-C) of the
      cAPK from Amblyomma americanum, which are probably produced from alternative RNA
      processing of a single cAPK-C gene. The cDNAs contain unique N-termini of
      variable lengths that are linked to a common region containing the alpha A helix,
      catalytic core, and a C-terminal tail. The common region is highly similar to
      both insect and vertebrate cAPK-Cs. We have examined mRNA profiles in whole ticks
      and in isolated salivary glands throughout feeding and find that a single cAPK-C
      isoform is expressed in the salivary glands of both unfed and feeding females.

PMID- 10070745
TI  - Early-replicating DNA from mosquito cells is associated with a distinct EcoRI
      fragment.
AB  - In an effort to define an origin of bi-directional DNA replication (OBR) in
      mosquito genomic DNA, we applied methods that take advantage of characteristic
      features of single-stranded DNA to methotrexate-resistant Aedes albopictus cells.
      The Mtx-5011-256 cells contained approximately 1000 copies of a 200 kb amplicon
      containing the dihydrofolate reductase locus, which likely contained one or more
      replication origins. When Mtx-5011-256 cells were synchronized by treatment with
      hydroxyurea, released into the S phase of the cell cycle, and labeled in vivo
      with tritiated DNA precursors, a 1.9 kb EcoRI fragment was preferentially labeled
      in EcoRI-digested genomic DNA. Similarly, we detected a 1.9 kb EcoRI fragment in
      DNA from wild type cells after cell cycle synchronization and in vivo labeling.
      In a complementary method, unlabeled single-stranded DNA was isolated from Mtx
      5011-256 cells, labeled in vitro, and hybridized to EcoRI-digested genomic DNA
      from mosquito cells. The labeled probe hybridized preferentially to a 1.9 kb
      fragment. Finally, a 1.9 kb EcoRI fragment was detected when nascent DNA was
      recovered from unsynchronized cells, made double-stranded by in vitro labeling,
      and digested with EcoRI. Taken together, these results suggest that in Aedes
      albopictus mosquito cells, many replication origins used at different times
      during S are flanked by EcoRI sites that define a 1.9 kb fragment, which has
      become more abundant in Mtx-5011-256 cells because it occurs in the dhfr
      amplicon. Tentative mapping of this origin to amplicon DNA remains ambiguous,
      further suggesting that a repeated sequence element occurs at or near the origin
      of replication.

PMID- 10070746
TI  - Mechanism of an insect glutathione S-transferase: kinetic analysis supporting a
      rapid equilibrium random sequential mechanism with housefly I1 isoform.
AB  - The steady-state kinetics of glutathione S-transferase I1 (GST I1) from housefly
      Musca domestica expressed in Escherichia coli were investigated with glutathione
      (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Concentrations of the varied
      substrates were from 0.03 to 1 mM for GSH and 0.05 to 1 mM for CDNB. Within this
      range, Michaelis-Menten behaviour was observed and convergent straight lines in
      double reciprocal plots excluded a ping-pong kinetic mechanism. Instead, data
      were consistent either with rapid-equilibrium random or with steady-state ordered
      sequential mechanisms because of abscissa convergence. Discrimination was
      achieved by studying the reaction with another electrophilic partner, p
      nitrophenyl-acetate (PNPA). Concentrations of PNPA and GSH varied within the
      ranges 0.5 to 10 mM and 0.03 to 0.6 mM, respectively. The complete set of data
      supports the proposal of a rapid-equilibrium random-sequential model with
      strictly independent sites for GSH and CDNB or PNPA. Kinetic parameters are thus
      true dissociation equilibrium constants with values of 0.15 mM for GSH, 0.15 mM
      for CDNB, and 7 mM for PNPA. Analysis of the inhibition by the product (S-(2,4
      dinitrophenyl)-glutathione, 10 to 100 microM), on the coupling reaction between
      GSH and CDNB with either GSH (0.05 to 0.5 mM, CDNB 0.2 mM) or CDNB (0.05 to 0.5
      mM, GSH 0.2 mM) varied, consistent with the proposed mechanism. Binding of
      product to the free enzyme excludes GSH (competitive inhibition pattern with Kp =
      12 microM) but only slightly hinders binding of CDNB. Binding free energies,
      together with the inhibition pattern, suggest that the non-peptidic moiety of
      product interacts with an alternative sub-site within the large open pocket
      accommodating the various electrophilic substrates. These results lead us to
      propose a model for intra-pocket shifting of the non-peptidic moiety upon product
      formation which contributes to the product release.

PMID- 10070748
TI  - Solution structure of human acidic fibroblast growth factor and interaction with
      heparin-derived hexasaccharide.
AB  - Fibroblast growth factors (FGFs) bind to extracellular matrices, especially
      heparin-like carbohydrates of heparan-sulfate proteoglycans which stabilize FGFs
      to protect against inactivation by heat, acid, proteolysis and oxidation.
      Moreover, binding of FGFs to cell surface proteoglycans promotes to form
      oligomers, which is essential for receptor oligomerization and activation. In the
      present study, we determined the solution structure of acidic FGF using a series
      of triple resonance multi-dimensional NMR experiments and simulated annealing
      calculations. Furthermore, we prepared the sample complexed with a heparin
      derived hexasaccharide which is a minimum unit for aFGF binding. From the
      chemical shift differences between free aFGF and aFGF-heparin complex, we
      concluded that the major heparin binding site was located on the regions 110-131
      and 17-21. The binding sites are quite similar to those observed for bFGF-heparin
      hexasaccharide complex, showing that both FGFs recognize heparin-oligosaccharides
      in a similar manner.

PMID- 10070749
TI  - Backbone resonance assignments of human UBC9.

PMID- 10070750
TI  - 1H, 13C, and 15N assignments and secondary structure of the high pH form of
      subunit c of the F1F0 ATP synthase.

PMID- 10070751
TI  - 1H, 13C and 15N backbone resonance assignment of Escherichia coli adenylate
      kinase, a 23.6 kDa protein.

PMID- 10070752
TI  - Assessing potential bias in the determination of rotational correlation times of
      proteins by NMR relaxation.
AB  - The various factors that influence the reliable and efficient determination of
      the correlation time describing molecular reorientation of proteins by NMR
      relaxation methods are examined. Nuclear Overhauser effects, spin-lattice, and
      spin-spin relaxation parameters of 15N NMR relaxation in ubiquitin have been
      determined at 17.6, 14.1, 11.7 and 9.4 Tesla. This unusually broad set of
      relaxation parameters has allowed the examination of the influence of chemical
      shift anisotropy, the functional form of the model-free spectral density, and the
      reliability of determined spin-spin relaxation parameters on the characterization
      of global tumbling of the protein. Treating the 15N chemical shift anisotropy
      (CSA) as an adjustable parameter, a consensus value of -170 +/- 15 ppm for the
      breadth of the chemical shift tensor and a global isotropic correlation time of
      4.1 ns are found when using the model-free spectral density to fit T1 and NOE
      data from all fields. The inclusion of T2 relaxation parameters in the
      determination of the global correlation time results in its increase to 4.6 ns.
      This apparent inconsistency may explain a large portion of the discrepancy often
      found between NMR- and fluorescence-derived tau m values for proteins. The near
      identity of observed T2 and T1 rho values suggests that contributions from slow
      motions are not the origin of the apparent inconsistency with obtained T1 and NOE
      data. Various considerations suggest that the origin of this apparent discrepancy
      may reside in a contribution to the spectral density at zero frequency that is
      not represented by the simple model-free formalism in addition to the usual
      experimental difficulties associated with the measurement of these relaxation
      parameters. Finally, an axially symmetric diffusion tensor for ubiquitin is
      obtained using exclusively T1 and NOE data. A recommendation is reached on the
      types and combinations of relaxation data that can be used to reliably determine
      tau m values. It is also noted that the reliable determination of tau m values
      from 15N T1 and NOE relaxation parameters will become increasingly difficult as
      tau m increases.

PMID- 10070753
TI  - Restrained molecular dynamics of solvated duplex DNA using the particle mesh
      Ewald method.
AB  - Restrained and unrestrained aqueous solution molecular dynamics simulations
      applying the particle mesh Ewald (PME) method to DNA duplex structures previously
      determined via in vacuo restrained molecular dynamics with NMR-derived restraints
      are reported. Without experimental restraints, the DNA decamer,
      d(CATTTGCATC).d(GATGCAAATG) and trisdecamer, d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT),
      structures are stable on the nanosecond time scale and adopt conformations in the
      B-DNA family. These free DNA simulations exhibit behavior characteristic of PME
      simulations previously performed on DNA sequences, including a low helical twist,
      frequent sugar pucker transitions, BI-BII(epsilon-zeta) transitions and coupled
      crakshaft (alpha-gamma) motion. Refinement protocols similar to the original in
      vacuo restrained molecular dynamics (RMD) refinements but in aqueous solution
      using the Cornell et al. force field [Cornell et al. (1995) J. Am. Chem. Soc.,
      117, 5179-5197] and a particle mesh Ewald treatment produce structures which fit
      the restraints very well and are very similar to the original in vacuo NMR
      structure, except for a significant difference in the average helical twist.
      Figures of merit for the average structure found in the RMD PME decamer
      simulations in solution are equivalent to the original in vacuo NMR structure
      while the figures of merit for the free MD simulations are significantly higher.
      The free MD simulations with the PME method, however, lead to some sequence
      dependent structural features in common with the NMR structures, unlike free MD
      calculations with earlier force fields and protocols. There is some suggestion
      that the improved handling of electrostatics by PME improves long-range
      structural aspects which are not well defined by the short-range nature of NMR
      restraints.

PMID- 10070754
TI  - Determination of order parameters and correlation times in proteins: a comparison
      between Bayesian, Monte Carlo and simple graphical methods.
AB  - We describe a novel approach to deducing order parameters and correlation times
      in proteins using a Bayesian statistical method, and show how likelihood
      contours, P(tau,S), and confidence levels can be obtained. These results are then
      compared with those obtained from a simple graphical method, as well as those
      from Monte Carlo simulations. The Bayes approach has the advantage that it is
      simple and accurate. Unlike Monte Carlo methods, it gives useful contour plots of
      probability (also not provided by the simple graphical method), and provides
      likelihood/confidence information. In addition, the Bayesian approach gives
      results in very good agreement with those obtained from Monte Carlo simulations,
      and as such use of Bayesian statistical methods appears to have a promising
      future for studies of order and dynamics in macromolecules.

PMID- 10070755
TI  - The effect of noncollinearity of 15N-1H dipolar and 15N CSA tensors and
      rotational anisotropy on 15N relaxation, CSA/dipolar cross correlation, and
      TROSY.
AB  - Current approaches to 15N relaxation in proteins assume that the 15N-1H dipolar
      and 15N CSA tensors are collinear. We show theoretically that, when there is
      significant anisotropy of molecular rotation, different orientations of the two
      tensors, experimentally observed in proteins, nucleic acids, and small peptides,
      will result in differences in site-specific correlation functions and spectral
      densities. The standard treatments of the rates of longitudinal and transverse
      relaxation of amide 15N nuclei, of the 15N CSA/15N-1H dipolar cross correlation,
      and of the TROSY experiment are extended to account for the effect of
      noncollinearity of the 15N-1H dipolar and 15N CSA (chemical shift anisotropy)
      tensors. This effect, proportional to the degree of anisotropy of the overall
      motion, (D parallel/D perpendicular - 1), is sensitive to the relative
      orientation of the two tensors and to the orientation of the peptide plane with
      respect to the diffusion coordinate frame. The effect is negligible at small
      degrees of anisotropy, but is predicted to become significant for D parallel/D
      perpendicular > or = 1.5, and at high magnetic fields. The effect of
      noncollinearity of 15N CSA and 15N-1H dipolar interaction is sensitive to both
      gross (hydrodynamic) properties and atomic-level details of protein structure.
      Incorporation of this effect into relaxation data analysis is likely to improve
      both precision and accuracy of the derived characteristics of protein dynamics,
      especially at high magnetic fields and for molecules with a high degree of
      anisotropy of the overall motion. The effect will also make TROSY efficiency
      dependent on local orientation in moderately anisotropic systems.

PMID- 10070756
TI  - Production of large quantities of isotopically labeled protein in Pichia pastoris
      by fermentation.
AB  - Heterologous expression in Pichia pastoris has many of the advantages of
      eukaryotic expression, proper folding and disulfide bond formation,
      glycosylation, and secretion. Contrary to other eukaryotic systems, protein
      production from P. pastoris occurs in simple minimal defined media making this
      system attractive for production of labeled proteins for NMR analysis. P.
      pastoris is therefore the expression system of choice for NMR of proteins that
      cannot be refolded from inclusion bodies or that require post-translational
      modifications for proper folding or function. The yield of expressed proteins
      from P. pastoris depends critically on growth conditions, and attainment of high
      cell densities by fermentation has been shown to improve protein yields by 10-100
      fold. Unfortunately, the cost of the isotopically enriched fermentation media
      components, particularly 15NH4OH, is prohibitively high. We report fermentation
      methods that allow for both 15N-labeling from (15NH4)2SO4 and 13C-labeling from
      13C-glucose or 13C-glycerol of proteins produced in Pichia pastoris. Expression
      of an 83 amino acid fragment of thrombomodulin with two N-linked glycosylation
      sites shows that fermentation is more cost effective than shake flask growth for
      isotopic enrichment.

PMID- 10070757
TI  - Conformational flexibility in calcitonin: the dynamic properties of human and
      salmon calcitonin in solution.
AB  - We have studied the dynamic properties of human (h) and salmon (s) calcitonin
      (CT) in solution. For both hormones, distance geometry in torsion-angle space has
      been used to generate three-dimensional structures consistent with NMR data
      obtained in sodium dodecyl sulfate micelles. For sCT and hCT we used,
      respectively, 356 and 275 interproton distances together with hydrogen-bonds as
      restraints. To better characterize their flexibility and dynamic properties two
      fully unrestrained 1100-ps molecular dynamics (MD) simulations in methanol were
      performed on the lowest-energy structures of both hormones. Statistical analyses
      of average geometric parameters and of their fluctuations performed in the last
      1000 ps of the MD run show typical helical values for residues 9-19 of sCT during
      the whole trajectory. For hCT a shorter helix was observed involving residues 13
      21, with a constant helical region in the range 13-19. Angular order parameters
      S(phi) and S(psi) indicate that hCT exhibits a higher flexibility, distributed
      along the whole chain, including the helix, while the only flexible amino acid
      residues in sCT connect three well-defined domains. Finally, our study shows that
      simulated annealing in torsion-angle space can efficiently be extended to NMR
      based three-dimensional structure calculations of helical polypeptides.
      Furthermore, provided that a sufficient number of NMR restraints describes the
      system, the method allows the detection of equilibria in solution. This
      identification occurs through the generation of 'spurious' high-energy
      structures, which, for right-handed alpha-helices, are likely to be represented
      by left-handed alpha-helices.

PMID- 10070758
TI  - A doublet-separated sensitivity-enhanced HSQC for the determination of scalar and
      dipolar one-bond J-couplings.
AB  - A simple, sensitivity-enhanced HSQC experiment is described which separates the
      upfield and downfield components in the indirect dimension into different
      subspectra. The sequence is similar to the generalized TROSY scheme; however,
      decoupling of the X-nucleus is used during detection. A detailed analysis of
      relaxation effects, precision and sensitivity of the method is presented. The
      approach is demonstrated in a two-dimensional water flip-back 1H-15N HSQC which
      measures 1JHN splittings in isotropic and oriented samples of ubiquitin and the
      hepatitis C protease. The results are in excellent agreement with splittings
      obtained from a conventional 1H-coupled HSQC.

PMID- 10070759
TI  - Bicelle-based liquid crystals for NMR-measurement of dipolar couplings at acidic
      and basic pH values.
AB  - It is demonstrated that mixtures of ditetradecyl-phosphatidylcholine or didodecyl
      phoshatidylcholine and dihexyl-phosphatidylcholine in water from lyotropic liquid
      crystalline phases under similar conditions as previously reported for bicelles
      consisting of dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl
      phosphatidylcholine (DHPC). The carboxy-ester bonds present in DMPC and DHPC are
      replaced by ether linkages in their alkyl analogs, which prevents acid- or base
      catalyzed hydrolysis of these compounds. 15N-1H dipolar couplings measured for
      ubiquitin over the 2.3-10.4 pH range indicate that this protein retains a
      backbone conformation which is very similar to its structure at pH 6.5 over this
      entire range.

PMID- 10070760
TI  - Backbone and C beta assignments of the anti-gp120 antibody Fv fragment complexed
      with an antigenic peptide.

PMID- 10070761
TI  - Sequence-specific 1H, 15N and 13C assignment of adenylate kinase from Escherichia
      coli in complex with the inhibitor AP5A.

PMID- 10070762
TI  - Expression and assignment of the 1H, 15N, and 13C resonances of the C-terminal
      domain of the diphtheria toxin repressor.

PMID- 10070763
TI  - Two ion-exchange chromatographic methods for the isolation of antibacterial
      peptides from lactoferrin. In situ enzymatic hydrolysis on an ion-exchange
      membrane.
AB  - Two ion-exchange chromatographic methods are reported for the rapid isolation of
      antibacterial peptides from lactoferrin (LF). Using the first method, a pepsin
      hydrolysate of LF was fractionated by bead-based cation-exchange chromatography.
      After removal of weakly bound material by washing with ammonia, highly purified
      lactoferricin-B (LFcin-B) was obtained in a single step by elution with 2 M NaCl.
      Some other cationic peptides, copurified as minor components, were also
      characterised by N-terminal sequencing, mass spectrometry and antibacterial
      activity determination. With the second method, cheese whey was filtered through
      a cation-exchange membrane, and the selectively bound LF was directly hydrolysed
      in situ with pepsin. Inactive LF fragments were washed off the membrane with
      ammonia, and a fraction enriched in LFcin-B was obtained by further elution with
      2 M NaCl. The membrane method is more rapid and offers several economic
      advantages.

PMID- 10070764
TI  - Rapid drug metabolite profiling using fast liquid chromatography, automated
      multiple-stage mass spectrometry and receptor-binding.
AB  - Rapid drug metabolite profiling can be achieved using fast chromatographic
      separation and fast mass spectrometric scanning without compromising the
      separation efficiency. Fast chromatographic separations of drug and its
      metabolites can be achieved by eluting from a short narrow-bore guard cartridge
      column (20 x 2 mm I.D., 3 microns BDS Hypersil C8) at flow-rate of 1.0 ml/min and
      with a gradient volume greater than 90 column volumes. The need for
      chromatographic separation is important for automated data dependent multiple
      stage mass spectrometry (MSn) experimentation. The total analysis time of 8 min
      permits profiling of metabolites in a 96-well plate in 13 h. The narrow
      chromatographic peaks resulting from the high flow-rate require the use of a mass
      spectrometer capable of fast scan speed due to the need to perform multiple MS
      experiments within the same chromatographic analysis. A method has been developed
      for screening potentially biologically active in vitro microsomal metabolites by
      affinity binding with a receptor. After separation by centrifugal
      ultrafiltration, the bound ligands are released and characterized by LC-MS. In
      vitro microsomal metabolites of tamoxifen, raloxifene and adatanserin were
      screened for potential biological activity using this method. The in vitro
      metabolites of tamoxifen captured by the receptor include N-demethyltamoxifen and
      three species of hydroxytamoxifen; these data are consistent with those from a
      conventional binding study and bioassay. In addition, both hydroxyraloxifene and
      dihydroxyraloxifene are also recognized by the receptor. The specificity of the
      molecular recognition process is illustrated by the absence of binding with
      control microsomal incubate and with adatanserin and its metabolites. Therefore,
      active metabolites can be rapidly profiled by fast LC, automated MSn, and
      receptor binding. This information can be obtained quickly and can add value to
      the drug discovery process.

PMID- 10070765
TI  - Comparative studies of the leachate of an industrial landfill by gas
      chromatography-mass spectrometry, liquid chromatography-nuclear magnetic
      resonance and liquid chromatography-mass spectrometry.
AB  - Nowadays, the need to have a realistic characterization of industrial effluents
      in the environment has become more and more recognized. A palette of different
      analytical methods both for sample extraction and instrumental analysis are
      available today, some older, others introduced more recently. The aim of this
      research is to compare a number of these techniques. To do this we studied a real
      leachate from an industrial landfill and carried out chemical analyses for
      organic pollutants, using different extraction methods based on solid-phase
      extraction and solid-phase microextraction and different instrumental techniques
      such as GC-MS, LC-MS, NMR and LC-NMR. Results show the performances of the
      different techniques, which are complementary.

PMID- 10070766
TI  - Preparation of an IMI dye (imidazole functional group) containing a 4-(N,N
      dimethylaminosulfonyl)-2,1,3-benzoxadiazole fluorophore for labeling of
      phosphomonoesters.
AB  - We are studying dye-imidazole conjugates ("IMI dyes") as reagents for labeling
      phosphomonoesters such as nucleotides. Previously we have employed a BODIPY dye
      in our IMI reagents, and analyzed the labeled products by capillary
      electrophoresis with laser-induced fluorescence detection (CE-LIF) involving an
      argon ion laser. (The BODIPY fluorophore is a 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene). Here we broaden the technology by preparing a DBD-IMI dye [DBD = 4
      (N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole], and using a helium-cadmium
      laser. While DBD-IMI (IMI3) is about 50x more stable photolytically than a BODIPY
      IMI dye (IMI2, a conjugate of a BODIPY dye with histamine, was tested), the
      detection limit for IMI2 (5.10(-11) M; S/N = 5, CE-LIF with an argon ion laser)
      is tenfold better than that for IMI3 (5.10(-10) M, S/N = 5, helium-cadmium
      laser). IMI3 conjugates of the four major DNA nucleotides were prepared and
      detected by CE-LIF.

PMID- 10070767
TI  - Continuous superporous agarose beds for chromatography and electrophoresis.
AB  - Continuous agarose beds (monoliths) were prepared by casting agarose emulsions
      designed to generate superporous agarose. The gel structures obtained were
      transected by superpores (diameters could be varied in the range 20-200 microns)
      through which liquids could be pumped. The pore structure and the basic
      properties of the continuous gel were investigated by microscopy and size
      exclusion chromatography. The chromatographic behaviour was approximately the
      same as for beds packed with homogeneous agarose beads with a particle diameter
      equivalent to the distance between the superpores. In one application, the
      superporous continuous agarose bed was derivatized with a NAD+ analogue and used
      in the affinity purification of bovine lactate dehydrogenase from a crude
      extract. In another application, a new superporous composite gel material was
      prepared by adding hydroxyapatite particles to the agarose phase. The composite
      bed was used to separate a protein mixture by hydroxyapatite chromatography. In a
      third application, the continuous superporous agarose material was used as an
      electrophoresis gel. Here, a water-immiscible organic liquid was pumped through
      the superpores to dissipate the joule heat evolved, thus allowing high current
      densities.

PMID- 10070768
TI  - Quantitative analysis of xanthohumol and related prenylflavonoids in hops and
      beer by liquid chromatography-tandem mass spectrometry.
AB  - A method for quantitation of six prenylflavonoids (xanthohumol, isoxanthohumol,
      desmethylxanthohumol, 6- and 8-prenylnaringenins and 6-geranylnaringenin) in hops
      and beer by HPLC-tandem mass spectrometry has been developed. The method allows
      direct analysis of beer and crude methanolic extracts of hops. After HPLC
      separation, prenylflavonoids were detected by positive ion multiple-reaction
      monitoring using a triple-quadrupole mass spectrometer equipped with a heated
      nebulizer--atmospheric pressure chemical ionization interface. The accuracy and
      precision were evaluated by replicate analyses of (spiked) samples. Thirteen
      commercial beers were analysed with the method. Isoxanthohumol, formed by
      isomerization of xanthohumol during the brewing process, was the most abundant
      flavonoid in hopped beers, ranging from 0.04 to 3.44 mg/l.

PMID- 10070769
TI  - Temperature, eluent flow-rate and column effects on the retention and
      quantitation properties of phenylthiocarbamyl derivatives of amino acids in
      reversed-phase high-performance liquid chromatography.
AB  - The separation and identification possibilities of 27 PTC-amino acids (with
      particular attention to those present in apples in free forms), are reported on
      seven RP columns such as, Nucleosil, 3 and 5 microns: 150(+20 guard) x 4.0 mm;
      Gromsil 3 microns; 150(+10 guard) x 4.0 mm; Hypersil 5 microns: 130(+20 guard) x
      4.0 mm, 150(+20 guard) x 4.0 mm and 200(+20 guard) x 4.0 mm, as well as, Hypersil
      3 microns: 150(+20 guard) x 4.0 mm: a UV range photodiode array (PDA) detection
      was employed. Optimization studies carried out in model solutions, as a function
      of the temperature (30-55 degrees C) and flow-rate (0.8-2.5 ml/min) of eluents
      proved that optimum resolutions are associated with the highest flow-rate
      applicable, (remaining on the safe side with a column pressure of < 3500 p.s.i.,
      1 p.s.i. = 6894.76 Pa), in the temperature range of 30-50 degrees C. Twenty-seven
      amino acids, characteristic in apples in free forms, have been separated and
      determined on all seven columns, performing the same gradient program, (the main
      component asparagine, present in overwhelming excess, and the minor constituents
      glutamine, beta-alanine, gamma-aminobutyric acid, homoserine, homoarginine and 1
      aminocyclopropane-1-carboxylic acid). Optimum conditions, at 2.1 ml/min, at 50
      degrees C, with 40 min run time, including equilibration, have been obtained with
      the Hypersil, 150(+20 guard) x 4 mm column, performing elutions. Responses of the
      corresponding amino acids proved to be independent of the column used;
      reproducibility in the concentration range of 15-1500 pmol was < 4.0% R.S.D.
      (relative standard deviation). Detailed study of the PDA spectra revealed that in
      addition to the identification/peak purity possibilities further characteristics
      can be obtained taking advantage of the difference in maximum values and of those
      of their special ratio values, respectively. The utility of the protocol was
      shown in the quantitation of the free amino acid content of three apple
      varieties.

PMID- 10070770
TI  - Effect of electric field on liquid chromatographic separation of peptide digests.
      Combining capillary separation techniques.
AB  - A system is described which allows operation of a range of capillary based liquid
      phase separations including capillary electrophoresis, isocratic and gradient
      capillary electrochromatography, isocratic and gradient capillary liquid
      chromatography and electrically assisted gradient capillary liquid
      chromatography. The system was coupled to electrospray ionization mass
      spectrometry in the electrically assisted capillary liquid chromatography mode to
      investigate the effect of applied voltage on the selectivity in peptide mapping
      separations. Analyses were performed on tryptic digests of recombinant human
      growth hormone and tissue plasminogen activator. The results show a small but
      useful effect on selectivity that can be used to fine tune specific separations.

PMID- 10070771
TI  - In-situ derivatisation of degradation products of chemical warfare agents in
      water by solid-phase microextraction and gas chromatographic-mass spectrometric
      analysis.
AB  - A new analytical procedure was developed for the extraction of degradation
      products of chemical warfare agents from water and for in-situ derivatisation
      prior to analysis by gas chromatography-mass spectrometry (GC-MS). With this new
      procedure, degradation products of the chemical warfare agents can be analysed
      and identified without going through laborious sample preparation. Parameters
      such as fiber selection, pH, salt content, derivatisation temperature, extraction
      and derivatisation periods, and sequence of adsorption/derivatisation were
      experimented with, to optimise the efficiency of this method. The detection limit
      is in the ppb to sub-ppb range with GC-MS in the full scan mode. Based on six
      injections of the devised procedure, a relative standard deviation from 10-35%
      can be achieved, depending on the compound. This method was demonstrated during
      the 4th International Interlaboratory Proficiency Test organised by the
      Organisation for the Prohibition of Chemical Weapons to be comparable to existing
      recommended operating procedures for verification of degradation products of
      chemical warfare agents.

PMID- 10070772
TI  - Detection of neutral and charged mutations in alpha- and beta-human globin chains
      by capillary zone electrophoresis in isoelectric, acidic buffers.
AB  - A simple and reliable method, for screening for point mutations in alpha- and
      beta-human globin chains, is reported here, utilizing capillary zone
      electrophoresis in isoelectric, acidic buffers. A solution of 50 mM iminodiacetic
      acid (pI 2.23) containing 7 M urea and 0.5% hydroxyethylcellulose (apparent pH
      3.2) is used as background electrolyte for fast separation of heme-free,
      denatured globin (alpha and beta) chains. Due to the low conductivity of such
      buffers, high voltage gradients (600 V/cm) can be applied, thus reducing the
      separation time to only a few minutes. In presence of neutral to neutral amino
      acid substitutions, it is additionally shown that the inclusion of 3% surfactant
      (Tween 20) in the sample and background electrolyte induces the separation of the
      wild-type and mutant chains, probably by a mechanism of hydrophobic interaction
      of the more hydrophobic mutant with the detergent micelle, via a mechanism
      similar to "micellar electrokinetic chromatography". At this low operative pH,
      however, charged mutants, involving substitutions of acidic amino acids (Glu and
      Asp) are not detected, since these residues are extensively protonated.
      Curiously, however, they are still separated in presence of detergent, due to the
      large variation in hydrophobicity involved in such mutations. Of the 19 mutants
      analyzed, all but one were resolved: Hb St Nazaire (beta 103 Phe-->Ile). This is
      due to the fact that the delta G (in kcal/mol) in the substitution Phe-->Ile is
      zero, thus no separation can possibly take place between two chains exhibiting
      the same hydrophobicity parameter.

PMID- 10070773
TI  - Validation of capillary electrophoresis in the analysis of ewe's milk casein.
AB  - Recent investigations have shown that capillary electrophoresis (CE) can be an
      alternative to other techniques such as polyacrylamide gel electrophoresis (PAGE)
      or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the
      qualitative analysis and separation of the different casein fractions in cow's
      and ewe's milk. However, past work has not yet clarified whether that method can
      achieve good quantifications. The present study has used a commercial whole ovine
      casein standard and a mixture of the standard and whole casein extracted from
      ewe's milk cheese to test the reliability of the technique. The results show that
      CE was able to quantify the ewe's milk caseins. The areas under four of the most
      representative peaks on the electrophoretogram for two alpha and two beta-caseins
      (designated alpha-casein1CE, alpha-casein2CE, beta-casein1CE, and beta-casein2CE
      in order of elution) were used to validate the method. In relation to linearity,
      coefficient of determination (r2) values greater than 99% were obtained for the
      regressions of each of the caseins. Moreover, each casein yielded response
      factors with a relative standard deviation (R.S.D.) of less than or equal to 5.
      The coefficients obtained in the day-to-day reproducibility analysis were higher
      than those for the same-day repeatability, but all the values were within
      acceptable limits. In the study of accuracy, the percentage recovery rates for
      the alpha-casein fractions were higher than those for the beta-casein fractions,
      hence quantification of the latter using this technique would appear to be more
      accurate under the conditions employed.

PMID- 10070774
TI  - Identification of illudins in Omphalotus nidiformis and Omphalotus olivascens
      var. indigo by column liquid chromatography-atmospheric pressure chemical
      ionization tandem mass spectrometry.
AB  - Reversed-phase liquid chromatography was used to separate toxins in mushrooms of
      the genus Omphalotus. Crude ethyl acetate extracts of cultures were injected
      directly onto a 150 x 2 mm I.D. column packed with 3 microns octadecylsilica and
      eluted with a gradient of acetonitrile in 0.1% aqueous acetic acid at a flow-rate
      of 200 microliters/min. Monitoring of the column effluate by atmospheric pressure
      ionization tandem mass spectrometry allowed the identification of the toxins. The
      fungal toxins illudin M and illudin S were detected and identified for the first
      time in cultures of the Australian Omphalotus nidiformis and the North American
      Omphalotus olivascens var. indigo (Boletales, Basidiomycetes) and confirmed the
      valuable taxonomic character of illudins for the genus Omphalotus.

PMID- 10070775
TI  - High-performance liquid chromatographic method for the comparison of the
      photostability of five sunscreen agents.
AB  - Sunscreen agents are commonly used in cosmetic products to filter out noxious
      radiation in sunlight. A convenient high-performance liquid chromatographic
      (HPLC) method for the quantification of five sunscreens after irradiation has
      been selected. We used this analytical method to compare the photostability of
      benzophenone-3, PEG-25 PABA, octyl dimethyl PABA, 4-methylbenzylidene camphor and
      butyl methoxydibenzoylmethane, at levels in the range of 25-60 microM. The assay
      was carried out, using a C8 column with a methanol--water mobile phase. The
      detector was set at a wavelength of 300 nm. The assay was linear with the
      following limits: 0.2 microgram ml-1 for benzophenone-3, 1 microgram ml-1 for PEG
      25 PABA, 0.15 microgram ml-1 for octyl dimethyl PABA, 0.1 microgram ml-1 for
      methylbenzylidene camphor and 0.05 microgram ml-1 for butyl
      methoxydibenzoylmethane. The half-lives calculated indicate a very good
      photostability of the sunscreens studied and permit to classify amongst
      themselves.

PMID- 10070777
TI  - Inheritance of nuclear DNA markers in gynogenetic haploid pink salmon.
AB  - We describe the inheritance of 460 PCR-based loci in the polyploid-derived pink
      salmon (Oncorhynchus gorbuscha) genome using gynogenetic haploid embryos. We
      detected a length polymorphism in a growth hormone gene (GH-2) intron that is
      caused by an 81 bp insertion homologous to the 3' end of the salmonid short
      interspersed repetitive element (SINE) SmaI. Such insertion polymorphisms within
      species bring into question the use of SINEs as phylogenetic markers. We
      confirmed that a microsatellite locus encodes a PCR-null allele that is
      responsible for an apparent deficit of heterozygotes in a population sample from
      Prince William Sound. Another set of microsatellite primers amplified alleles of
      the same molecular weight from both loci of a duplicated pair. In our analysis of
      several PCR-based multilocus techniques, we failed to detect evidence of
      comigrating fragments produced by duplicated loci. Segregation analysis of PCR
      based markers using gynogenetic haploid embryos ensures that the interpretation
      of molecular variation is not complicated by heterozygosity, diploidy, or gene
      duplication. We urge investigators to test the inheritance of polymorphisms in
      salmonids prior to using them to measure genetic variation.

PMID- 10070780
TI  - Confocal laser scanning microscopy of hamster cerebellum using FM4-64 as
      intracellular staining.
AB  - The FM4-64, a member of the family of fluorescent dyes, has been applied to the
      cerebellar cortex to evaluate its properties as an intracellular stain and
      intracortical tracer. Slabs of hamster cerebellum, 1-2 mm thick, were incubated
      in 10, 30, and 100 microns solutions of FM4-64 in sodium phosphate buffer and
      observed in a slow scan confocal laser scanning microscope. Mossy and climbing
      fibers were traced in the cerebellar white and gray substances. They exhibited a
      high fluorescence signal at the level of the myelin sheath. Mossy fibers were
      identified in the granular layer by their typical rosette formation and
      dichotomous bifurcation pattern. Climbing fiber bundles were observed crossing
      the granular layer and giving collateral branches around Golgi cell bodies. They
      ascend to the Purkinje cell layer on their way to the molecular layer. Cerebellar
      macroneurons (Golgi and Purkinje cells) and microneurons (granule, basket, and
      stellate cells) showed optimal intracellular staining of cell soma, axonal, and
      dendritic processes. The z-series of stacks of optodigital sections allowed us to
      explore in depth the cytoarchitectonic arrangement, nerve and glial cell
      morphology, and the topographic relationship with the afferent fibers.

PMID- 10070781
TI  - Apoptotic pathways depend on the target enzymatic activity and not on the
      triggering agent.
AB  - Molt-4 human leukemia cells were triggered to apoptosis by various agents with
      different mechanisms of action. Staurosporine, a protein kinase C (PKC)
      inhibitor; camptothecin, a topoisomerase I blocking drug; and tiazofurin, an
      inhibitor of inosine 5'-phosphate dehydrogenase (IMPDH), were used.
      Ultrastructural analysis showed morphologic changes characteristic of apoptosis
      that were very similar for all three agents. Nevertheless, DNA oligonucleosomic
      fragmentation was not detectable by agarose gel electrophoresis. However, a
      genomic DNA cleavage appeared after pulse-field gel electrophoresis (PFGE) in
      cells treated with these agents for 24 h. Furthermore, in situ nick translation
      (NT) showed a finely spotted nuclear labelling in staurosporine-treated cells and
      a compact fluorescence after camptothecin incubation. In tiazofurin-treated cells
      an intermediate pattern was found. Therefore, apoptotic agents with different
      mechanisms of action induced the formation of large genomic DNA fragments and
      very similar ultrastructural changes. Therefore, both phenomena and the closely
      related apoptosis progression depend on target cell machinery and not on the
      triggering agent.

PMID- 10070782
TI  - Correlative light and backscattered electron microscopy of bone--Part I: Specimen
      preparation methods.
AB  - A method for preparing nondecalcified bone and tooth specimens for imaging by
      both light microscopy (LM) and backscattered electron microscopy in the scanning
      electron microscope (BSE-SEM) is presented. Bone blocks are embedded in a
      polymethylmethacrylate (PMMA) mixture and mounted on glass slides using
      components of a light-cured dental adhesive system. This method of slide
      preparation allows correlative studies to be carried out between different
      microscopy modes, using the same histologic section. It also represents a large
      time savings relative to other mounting methods whose media require long cure
      times.

PMID- 10070783
TI  - Commentary: progress in optimization of patient dose and image quality in x-ray
      diagnostics.

PMID- 10070784
TI  - Clinical relative biological effectiveness of low-energy x-rays emitted by
      miniature x-ray devices.
AB  - Several groups are developing ultra-miniature x-ray machines for clinical use in
      radiation therapy. Current systems are for interstitial radiosurgery and for
      intravascular insertion for irradiation to prevent re-stenosis. Typical
      generating voltages are low, in the 20 to 40 kV range. It is well established
      that the biological effectiveness of such low-energy photons is large compared
      with higher-energy gamma rays, because of the dominance of photoelectric
      absorption at low energies. We have used microdosimetric analyses to estimate
      RBEs for such devices, both at low doses and clinically relevant doses, relative
      to radiations from 60Co, 192Ir, 125I and 90Sr/90Y. The RBEs at clinically
      relevant doses and dose rates for these low-energy x-ray sources are considerably
      above unity, both relative to 60Co and to 192Ir photons, and also relative to
      125I and 90Sr/90Y brachytherapy sources. As a function of depth, the overall
      effect of the change in dose and the change in beam spectrum results in beams
      whose biologically weighted dose (dose x RBE) decreases with depth somewhat more
      slowly than does the physical dose. The estimated clinically relevant RBEs are
      sufficiently large that they should be taken into account during the treatment
      design stage.

PMID- 10070785
TI  - FDTD analysis of close-coupled 418 MHz radiating devices for human biotelemetry.
AB  - This paper describes the finite-difference time-domain (FDTD) analysis of antenna
      body interaction effects occurring when chest-mounted 418 MHz radio transmitters
      are used for medical telemetry applications. Whole-body software models
      (homogeneous, layered and tissue-segmented) were developed for an adult male
      subject. Using an electrically small (300 mm2) planar loop antenna, calculated
      radiation efficiencies ranged between 33.5% and 39.2% for a whole-body model, and
      between 60.7% and 66.1% for a torso; radiation patterns were found to be largely
      independent of model composition. The computed radiation efficiency for a 21.5 kg
      phantom representing a six-year-old female was within 1.1 dB of measured results
      (actual body mass 28 kg) and well-correlated azimuthal radiation patterns were
      noted.

PMID- 10070786
TI  - Membrane solubilization in erythrocytes as a measure of radiation exposure to
      fast neutrons.
AB  - Membrane solubilization and osmotic fragility of rat erythrocytes irradiated in
      vivo with fast neutron fluences ranging from 10(6) to 5 x 10(7) n cm(-2) using a
      252Cf source were measured instantaneously using a light scattering technique.
      The solubilization of erythrocyte membrane by a non-ionic detergent,
      octylglucoside (OG), was found to exhibit a two stage transition from vesicular
      form to mixed micellar form in the range of detergent concentrations 1.5-7.8 mM.
      The coexistence phase, vesicular/mixed micellar, was shifted towards higher
      detergent concentrations with increase in the neutron fluence, indicating
      increasing membrane resistance to the detergent and hence change in the natural
      membrane permeation properties. The technique shows an adequate sensitivity in
      detecting membrane damage in erythrocytes and has potential as a biophysical
      marker of radiation exposure. The osmotic fragility of irradiated erythrocytes
      shows a decreasing trend with increasing irradiation fluence measured directly
      and two weeks post-irradiation. Blood films photographed two weeks post
      irradiation show developed elliptocytosis and crenated cell anaemia.

PMID- 10070787
TI  - Dose errors in the near field of an HDR brachytherapy stepping source.
AB  - The dose rate at point P at 0.25 cm in water from the transverse bisector of a
      straight catheter with an active stepping source (Nucletron microSelectron HDR
      source) with a dwell length of 2 cm was calculated using Monte Carlo code MCNP
      4.A. The source step sizes were 1 cm and 0.25 cm. The Monte Carlo (MC) results
      were used for comparison with the results calculated with the Nucletron
      brachytherapy planning system (BPS) formalism, first with BPS variants and then
      with its respective MC calculated radial dose function and anisotropy function.
      The dose differences at point P calculated using the BPS formalism and variants
      are +15.4% and +3.1% for the source step size of 1 cm and 0.25 cm respectively.
      This reduction in dose difference is caused by the increased importance of errors
      in the anisotropy function with the smaller step size, which counter the errors
      in the radial dose function. Using the MC calculated radial dose function and
      anisotropy function with the BPS formalism. 1% dose calculation accuracy can be
      achieved, even in the near field, with negligible extra demand on computation
      time.

PMID- 10070788
TI  - A consistent formalism for the application of phantom and collimator scatter
      factors.
AB  - A coherent system for the use of scatter correction factors, determined at 10 cm
      depth, is described for dose calculations on the central axis of arbitrarily
      shaped photon beams. The system is suitable for application in both the fixed
      source-surface distance (SSD) and in the isocentric treatment set-up. This is in
      contrast to some other proposals where only one of these approaches forms the
      basis of the calculation system or where distinct quantities and data sets are
      needed. In order to derive the relations in the formalism, we introduced a
      separation of the phenomena related to the energy fluence in air and to the
      phantom scatter contribution to the dose. Both are used relative to quantities
      defined for the reference irradiation set-up. It is shown that dose calculations
      can be performed with only one set of basic beam data, obtained at a reference
      depth of 10 cm. These data consist for each photon beam quality of measured
      collimator and phantom scatter correction factors, in combination with a set of
      (percentage/relative) depth-dose or tissue-phantom ratio values measured along
      the central axis of the beam. Problems related to measurements performed at the
      depth of maximum absorbed dose, due to the electron contamination of the beam,
      are avoided in this way. Collimator scatter correction factors are obtained by
      using a mini-phantom, while phantom scatter correction factors are derived from
      measurements in a full scatter phantom in combination with the results of the
      mini-phantom measurements. For practical reasons the fixed SSD system was chosen
      to determine the data. Then, dose calculations in a fixed SSD treatment set-up
      itself are straightforward. Application in the isocentric treatment set-up needs
      simple conversion steps, while the inverse approach, from isocentric to fixed
      SSD, is described as well. Differences between the two approaches are discussed
      and the equations for the conversions are given.

PMID- 10070789
TI  - Constrained customization of non-coplanar beam orientations in radiotherapy of
      brain tumours.
AB  - A methodology for the constrained customization of non-coplanar beam orientations
      in radiotherapy treatment planning has been developed and tested on a cohort of
      five patients with tumours of the brain. The methodology employed a combination
      of single and multibeam cost functions to produce customized beam orientations.
      The single-beam cost function was used to reduce the search space for the
      multibeam cost function, which was minimized using a fast simulated annealing
      algorithm. The scheme aims to produce well-spaced, customized beam orientations
      for each patient that produce low dose to organs at risk (OARs). The customized
      plans were compared with standard plans containing the number and orientation of
      beams chosen by a human planner. The beam orientation constraint-customized plans
      employed the same number of treatment beams as the standard plan but with beam
      orientations chosen by the constrained-customization scheme. Improvements from
      beam orientation constraint-customization were studied in isolation by
      customizing the beam weights of both plans using a dose-based downhill simplex
      algorithm. The results show that beam orientation constraint-customization
      reduced the maximum dose to the orbits by an average of 18.8 (+/-3.8, ISD)% and
      to the optic nerves by 11.4 (+/-4.8, ISD)% with no degradation of the planning
      target volume (PTV) dose distribution. The mean doses, averaged over the patient
      cohort, were reduced by 4.2 (+/-1.1, ISD)% and 12.4 (+/-3.1, ISD)% for the orbits
      and optic nerves respectively. In conclusion, the beam orientation constraint
      customization can reduce the dose to OARs, for few-beam treatment plans, when
      compared with standard treatment plans developed by a human planner.

PMID- 10070790
TI  - A control systems approach for the simulation of renal dynamic software phantoms
      for nuclear medicine.
AB  - For renal dynamic studies, the COST B2 hybrid phantom is an example of an
      artificially created software phantom. Although this phantom is useful, it is not
      possible to implement the phantom in a self-consistent fashion to produce, for
      example, a collection of tracer in the bladder which is related to the flow from
      the kidneys. In this study control systems are used to provide a self-consistent
      model. A feed-forward control system was designed for the transport of DTPA in
      the human body using SIMULINK. The system is based on a three-compartment model
      described by a set of differential equations with flow rates which may be set by
      the operator. The differential uptake in the kidneys may also be specified, while
      the flow of tracer through the renal parenchyma and collecting system of each
      kidney is determined using two-parameter retention functions. Curves
      corresponding to normal or pathological conditions may be simulated for plasma,
      parenchyma, collecting system and bladder by appropriate selection of parameters.
      The system is user-friendly and can be used to simulate almost all conditions
      seen in patient studies. The next stage of using this information to design
      dynamic image simulations is in progress.

PMID- 10070791
TI  - Modelling the anisotropic electrical properties of skeletal muscle.
AB  - We present a numerical model used to analyse the anisotropic electrical
      properties of frog muscle, measured in vivo. The model represents the
      anisotropic, irregularly shaped muscle as a set of cubic elements. We develop a
      finite difference method to calculate the electrical resistance between two
      electrodes inserted longitudinally or transversely into the muscle in terms of
      longitudinal and transverse muscle conductivities. Comparison of the measured
      impedance values with the calculated resistances yields the separate variation
      with frequency of the two conductivity components. We also compare the results of
      the numerical, finite difference method with those of two simple, analytical
      models.

PMID- 10070792
TI  - A sensor-weighted overlapping-sphere head model and exhaustive head model
      comparison for MEG.
AB  - The spherical head model has been used in magnetoencephalography (MEG) as a
      simple forward model for calculating the external magnetic fields resulting from
      neural activity. For more realistic head shapes, the boundary element method
      (BEM) or similar numerical methods are used, but at greatly increased
      computational cost. We introduce a sensor-weighted overlapping-sphere (OS) head
      model for rapid calculation of more realistic head shapes. The volume currents
      associated with primary neural activity are used to fit spherical head models for
      each individual MEG sensor such that the head is more realistically modelled as a
      set of overlapping spheres, rather than a single sphere. To assist in the
      evaluation of this OS model with BEM and other head models, we also introduce a
      novel comparison technique that is based on a generalized eigenvalue
      decomposition and accounts for the presence of noise in the MEG data. With this
      technique we can examine the worst possible errors for thousands of dipole
      locations in a realistic brain volume. We test the traditional single-sphere
      model, three-shell and single-shell BEM, and the new OS model. The results show
      that the OS model has accuracy similar to the BEM but is orders of magnitude
      faster to compute.

PMID- 10070793
TI  - Simulation of dose distribution irradiation by the Leksell Gamma Unit.
AB  - The dose distributions in a spherical phantom irradiated by a Leksell Gamma Unit
      have been calculated using the EGS4 Monte Carlo code. In the simulation, the
      photon beams are considered to emanate from point sources, ignoring the
      scattering from source and collimating systems. The calculated results are in
      good agreement with results obtained with semiconductor diodes.

PMID- 10070794
TI  - Monte Carlo based protocol for cell survival and tumour control probability in
      BNCT.
AB  - A mathematical model to calculate the theoretical cell survival probability
      (nominally, the cell survival fraction) is developed to evaluate preclinical
      treatment conditions for boron neutron capture therapy (BNCT). A treatment
      condition is characterized by the neutron beam spectra, single or bilateral
      exposure, and the choice of boron carrier drug (boronophenylalanine (BPA) or
      boron sulfhydryl hydride (BSH)). The cell survival probability defined from
      Poisson statistics is expressed with the cell-killing yield, the 10B(n,alpha)7Li
      reaction density, and the tolerable neutron fluence. The radiation transport
      calculation from the neutron source to tumours is carried out using Monte Carlo
      methods: (i) reactor-based BNCT facility modelling to yield the neutron beam
      library at an irradiation port; (ii) dosimetry to limit the neutron fluence below
      a tolerance dose (10.5 Gy-Eq); (iii) calculation of the 10B(n,alpha)7Li reaction
      density in tumours. A shallow surface tumour could be effectively treated by
      single exposure producing an average cell survival probability of 10(-3)-10(-5)
      for probable ranges of the cell-killing yield for the two drugs, while a deep
      tumour will require bilateral exposure to achieve comparable cell kills at depth.
      With very pure epithermal beams eliminating thermal, low epithermal and fast
      neutrons, the cell survival can be decreased by factors of 2-10 compared with the
      unmodified neutron spectrum. A dominant effect of cell-killing yield on tumour
      cell survival demonstrates the importance of choice of boron carrier drug.
      However, these calculations do not indicate an unambiguous preference for one
      drug, due to the large overlap of tumour cell survival in the probable ranges of
      the cell-killing yield for the two drugs. The cell survival value averaged over a
      bulky tumour volume is used to predict the overall BNCT therapeutic efficacy,
      using a simple model of tumour control probability (TCP).

PMID- 10070795
TI  - Dosimetric verification of a commercial inverse treatment planning system.
AB  - A commercial three-dimensional (3D) inverse treatment planning system, Corvus
      (Nomos Corporation, Sewickley, PA), was recently made available. This paper
      reports our preliminary results and experience with commissioning this system for
      clinical implementation. This system uses a simulated annealing inverse planning
      algorithm to calculate intensity-modulated fields. The intensity-modulated fields
      are divided into beam profiles that can be delivered by means of a sequence of
      leaf settings by a multileaf collimator (MLC). The treatments are delivered using
      a computer-controlled MLC. To test the dose calculation algorithm used by the
      Corvus software, the dose distributions for single rectangularly shaped fields
      were compared with water phantom scan data. The dose distributions predicted to
      be delivered by multiple fields were measured using an ion chamber that could be
      positioned in a rotatable cylindrical water phantom. Integrated charge collected
      by the ion chamber was used to check the absolute dose of single- and multifield
      intensity modulated treatments at various spatial points. The measured and
      predicted doses were found to agree to within 4% at all measurement points.
      Another set of measurements used a cubic polystyrene phantom with radiographic
      film to record the radiation dose distribution. The films were calibrated and
      scanned to yield two-dimensional isodose distributions. Finally, a beam imaging
      system (BIS) was used to measure the intensity-modulated x-ray beam patterns in
      the beam's-eye view. The BIS-measured images were then compared with a
      theoretical calculation based on the MLC leaf sequence files to verify that the
      treatment would be executed accurately and without machine faults. Excellent
      correlation (correlation coefficients > or = 0.96) was found for all cases.
      Treatment plans generated using intensity-modulated beams appear to be suitable
      for treatment of irregularly shaped tumours adjacent to critical structures. The
      results indicated that the system has potential for clinical radiation treatment
      planning and delivery and may in the future reduce treatment complexity.

PMID- 10070796
TI  - An objective function for radiation treatment optimization based on local
      biological measures.
AB  - The implementation of biological optimization of radiation treatment plans is
      impeded by both computational and modelling problems. We derive an objective
      function from basic model assumptions which includes the normal tissue
      constraints as interior penalty functions. For organs that are composed of
      parallel subunits, a mean response model is proposed which leads to constraints
      similar to dose-volume constraints. This objective function is convex in the case
      when no parallel organs lie in the treatment volume. Otherwise, an argument is
      given to show that a number of local minima may exist which are near degenerate
      to the global minimum. Thus, together with the measure quality of the objective
      function, highly efficient gradient algorithms can be used. The number of
      essential biological model parameters could be reduced to a minimum. However, if
      the optimization constraints are given as TCP/NTCP values, Lagrange multiplier
      updates have to be performed by invoking comprehensive biological models.

PMID- 10070797
TI  - Registration using tomographic projection files.
AB  - An algorithm has been developed and experimentally verified for tomographic
      registration--a patient positioning method using internal anatomy and standard
      external fiducial marks. This algorithm improves patient set-up and verification
      to an accuracy sufficient for tomotherapy. By implementation of this technique,
      the time-consuming reconstruction process is avoided. Instead, offsets in the x,
      y and z directions are determined directly from sinogram data by an algorithm
      that utilizes cross-correlations and Fourier transforms. To verify the efficiency
      and stability of the algorithm, data were collected on the University of
      Wisconsin's dedicated tomotherapy research workbench. The experiment indicates
      offset statistical errors of less than +/-0.8 mm for offsets up to 30 mm. With
      standard clinical techniques, initial patient offsets are expected to be less
      than 5 mm, so the 30 mm limitation is of no consequence. The angular resolution
      for the direction of patient translation is within the +/-2 degrees needed for
      tomotherapy.

PMID- 10070798
TI  - The 'equivalent wedge' implementation of the Varian Enhanced Dynamic Wedge (EDW)
      into a treatment planning system.
AB  - The purpose of this work was to establish procedures for the implementation of
      the Varian Enhanced Dynamic Wedge into a treatment planning system (TPS), based
      as much as possible on simple theoretical considerations and already available
      data. A method is presented for the calculation (rather than measurement) of off
      axis relative wedge transmission curves that are required by the TPS for relative
      dose calculations. We also present a method for absolute dose (monitor unit)
      calculations, based on the calculation of an effective wedge factor on the
      prescription point. A simple formula has been derived for the calculation of the
      effective wedge factor for the most general case, i.e. an arbitrary effective
      wedge angle, field size and prescription point. Relative dose calculations have
      been verified by measurements performed on a Varian Clinac 2300C/D linear
      accelerator, for 6 MV and 20 MV photon energies. Monitor unit calculations have
      also been verified experimentally for several cases such as symmetric and
      asymmetric fields with prescription on the collimator axis or on the geometrical
      centre of the asymmetric field. The presented technique provides results within
      2% for both relative and absolute dose calculations for clinically relevant
      cases.

PMID- 10070799
TI  - Experimental validation of arthroscopic cartilage stiffness measurement using
      enzymatically degraded cartilage samples.
AB  - In order to evaluate the ability of the arthroscopic indentation instrument,
      originally developed for the measurement of cartilage stiffness during
      arthroscopy, to detect cartilage degeneration, we compared changes in the
      stiffness with the structural and constitutional alterations induced by enzymes
      on the tissue in vitro. The culturing of osteochondral plugs on Petri dishes was
      initiated in Minimum Essential Medium with Earle's salts and the baseline
      stiffness was measured. Then, the experimental specimens were digested using 50
      microg ml(-1) trypsin for 24 h, 0.1 U ml(-1) chondroitinase ABC or 30 U ml(-1)
      purified collagenase (type VII) for 24 h or 48 h (n = 8-15 per group). The
      control specimens were incubated in the medium. After the enzyme digestion, the
      end-point stiffness was measured and the specimens for the microscopic analyses
      were processed. The proteoglycan (PG) distribution was analysed using
      quantitative microspectrophotometry and the quantitative evaluation of the
      collagen network was made using a computer-based polarized light microscopy
      analysis. Decrease (p < 0.05) of cartilage stiffness was found after 24 h trypsin
      (36%) and 48 h chondroitinase ABC (24%) digestion corresponding to a decrease (p
      < 0.01) of up to 80% and up to 30% in the PG content respectively. Decrease of
      the superficial zone collagen content or arrangement (78%, p < 0.001) after 48 h
      collagenase digestion also induced a decrease (30%, p < 0.001) in cartilage
      stiffness. We conclude that our instrument is capable of detecting early
      structural and compositional changes related to cartilage degeneration.

PMID- 10070800
TI  - A search for improved technique factors in paediatric fluoroscopy.
AB  - A Monte Carlo computational model of a fluoroscopic imaging chain was used for
      deriving optimal technique factors for paediatric fluoroscopy. The optimal
      technique was defined as the one that minimizes the absorbed dose (or dose rate)
      in the patient with a constraint of constant image quality. Image quality was
      assessed for the task of detecting a detail in the image of a patient-simulating
      phantom, and was expressed in terms of the ideal observer's signal-to-noise ratio
      (SNR) for static images and in terms of the accumulating rate of the square of
      SNR for dynamic imaging. The entrance air kerma (or air kerma rate) and the mean
      absorbed dose (or dose rate) in the phantom quantified radiation detriment. The
      calculations were made for homogeneous phantoms simulating newborn, 3-, 10- and
      15-year-old patients, barium and iodine contrast material details, several x-ray
      spectra, and for imaging with or without an antiscatter grid. The image receptor
      was modelled as a CsI x-ray image intensifier (XRII). For the task of detecting
      low- or moderate-contrast iodine details, the optimal spectrum can be obtained by
      using an x-ray tube potential near 50 kV and filtering the x-ray beam heavily.
      The optimal tube potential is near 60 kV for low- or moderate-contrast barium
      details, and 80-100 kV for high-contrast details. The low-potential spectra above
      require a high tube load, but this should be acceptable in paediatric
      fluoroscopy. A reasonable choice of filtration is the use of an additional 0.25
      mm Cu, or a suitable K-edge filter. No increase in the optimal tube potential was
      found as phantom thickness increased. With the constraint of constant low
      contrast detail detectability, the mean absorbed doses obtained with the above
      spectra are approximately 50% lower than those obtained with the reference
      conditions of 70 kV and 2.7 mm Al filter. For the smallest patient and x-ray
      field size, not using a grid was slightly more dose-efficient than using a grid,
      but when the patient size and field size were increased a fibre interspaced grid
      resulted in lower doses than imaging without a grid. For a 15-year-old patient
      the mean absorbed doses were up to 40% lower with this grid than without the
      grid.

PMID- 10070801
TI  - Single-slice rebinning method for helical cone-beam CT.
AB  - In this paper, we present reconstruction results from helical cone-beam CT data,
      obtained using a simple and fast algorithm, which we call the CB-SSRB algorithm.
      This algorithm combines the single-slice rebinning method of PET imaging with the
      weighting schemes of spiral CT algorithms. The reconstruction is approximate but
      can be performed using 2D multislice fan-beam filtered backprojection. The
      quality of the results is surprisingly good, and far exceeds what one might
      expect, even when the pitch of the helix is large. In particular, with this
      algorithm comparable quality is obtained using helical cone-beam data with a
      normalized pitch of 10 to that obtained using standard spiral CT reconstruction
      with a normalized pitch of 2.

PMID- 10070802
TI  - Developments in component-based normalization for 3D PET.
AB  - Normalization in positron emission tomography (PET) is the process of ensuring
      that all lines of response joining detectors in coincidence have the same
      effective sensitivity. In three-dimensional (3D) PET, normalization is
      complicated by the presence of a large proportion of scattered coincidences, and
      by the fact that cameras operating in 3D mode encounter a very wide range of
      count-rates. In this work a component-based normalization model is presented
      which separates the normalization of true and scattered coincidences and accounts
      for variations in normalization effects with count-rate. The effects of the
      individual components in the model on reconstructed images are investigated, and
      it is shown that only a subset of these components has a significant effect on
      reconstructed image quality.

PMID- 10070803
TI  - Internal absorbed dose estimation by a TLD method for 18F-FDG and comparison with
      the dose estimates from whole body PET.
AB  - The thermoluminescent dosimeter (TLD) method has been proposed as a useful tool
      for estimating internal radiation absorbed dose in nuclear medicine. An efficient
      approach to verify the accuracy of the TLD method has been performed in this
      study. Under the standard protocol for 2-[F-18]fluoro-2-deoxy-D-glucose (18F
      FDG), whole body PET experiments and simultaneous body surface dose measurements
      by TLDs were performed on six normal volunteers. By using the body surface dose
      measured with TLDs, the cumulated activities of nine source organs were estimated
      with a mathematical unfolding technique for three different initial guesses. The
      accuracy of the results obtained by the TLD method was investigated by comparison
      with the actual cumulated activity of the same source organs measured by whole
      body PET. The cumulated activities of the source organs obtained by the TLD
      method and whole body PET show a significant correlation (correlation
      coefficient, r > 0.98, level of confidence, p < 0.001) with each other. The mean
      effective doses in this study are 3.2 x 10(-2) mSv MBq(-1) obtained from the TLD
      method and 2.9 x 10(-2) mSv MBq(-1) obtained from the whole body PET. Good
      agreement between the results of the TLD method and whole body PET was observed.

PMID- 10070804
TI  - Comparison of four magnetic resonance methods for mapping small temperature
      changes.
AB  - Non-invasive detection of small temperature changes (< 1 degree C) is pivotal to
      the further advance of regional hyperthermia as a treatment modality for deep
      seated tumours. Magnetic resonance (MR) thermography methods are considered to be
      a promising approach. Four methods exploiting temperature-dependent parameters
      were evaluated in phantom experiments. The investigated temperature indicators
      were spin-lattice relaxation time T1, diffusion coefficient D, shift of water
      proton resonance frequency (water PRF) and resonance frequency shift of the
      methoxy group of the praseodymium complex (Pr probe). The respective pulse
      sequences employed to detect temperature-dependent signal changes were the
      multiple readout single inversion recovery (T One by Multiple Read Out Pulses;
      TOMROP), the pulsed gradient spin echo (PGSE), the fast low-angle shot (FLASH)
      with phase difference reconstruction, and the classical chemical shift imaging
      (CSI). Applying these sequences, experiments were performed in two separate and
      consecutive steps. In the first step, calibration curves were recorded for all
      four methods. In the second step, applying these calibration data, maps of
      temperature changes were generated and verified. With the equal total acquisition
      time of approximately 4 min for all four methods, the uncertainties of
      temperature changes derived from the calibration curves were less than 1 degree C
      (Pr probe 0.11 degrees C, water PRF 0.22 degrees C, D 0.48 degrees C and T1 0.93
      degrees C). The corresponding maps of temperature changes exhibited slightly
      higher errors but still in the range or less than 1 degree C (0.97 degrees C,
      0.41 degrees C, 0.70 degrees C, 1.06 degrees C respectively). The calibration
      results indicate the Pr probe method to be most sensitive and accurate. However,
      this advantage could only be partially transferred to the thermographic maps
      because of the coarse 16 x 16 matrix of the classical CSI sequence. Therefore, at
      present the water PRF method appears to be most suitable for MR monitoring of
      small temperature changes during hyperthermia treatment.

PMID- 10070805
TI  - Comparing two methods for calculating phantom scatter.
AB  - Two methods are compared for calculating the field-size dependence of the phantom
      scatter component of dose for x-ray beams. One model sums three Gaussian
      distributions; the other model is a two-parameter function. With a measurement of
      the beam quality as input to determine parameters, both models accurately
      reproduce the relative phantom scatter. However, there are important differences
      between the models. For all beam energies, the two-parameter model characterizes
      the absolute phantom scatter as a function of depth and field size, while, also
      for all beam energies, the six-parameter Gaussian model characterizes the
      relative phantom scatter at a single depth of 10 cm. For small field sizes, the
      phantom scatter calculated from the two-parameter model agrees with Monte Carlo
      calculations better than the Gaussian model. In the Gaussian model, the
      parameters can be obtained for beam energies between 60Co and 25 MV by linear
      interpolation based on the measured beam quality. In the two-parameter model, and
      for energies above 4 MV, the parameters can be obtained using linear functions of
      the dose-weighted average linear attenuation coefficient, which is related to
      beam quality.

PMID- 10070806
TI  - A technique for manual definition of an irregular volume of interest in single
      photon emission computed tomography.
AB  - A technique is described for manually outlining a volume of interest (VOI) in a
      three-dimensional SPECT dataset. Regions of interest (ROIs) are drawn on three
      orthogonal maximum intensity projections. Image masks based on these ROIs are
      backprojected through the image volume and the resultant 3D dataset is segmented
      to produce the VOI. The technique has been successfully applied in the exclusion
      of unwanted areas of activity adjacent to the brain when segmenting the organ in
      SPECT imaging using 99mTc HMPAO. An example of its use for segmentation in tumour
      imaging is also presented. The technique is of value for applications involving
      semi-automatic VOI definition in SPECT.

PMID- 10070807
TI  - Low monitor units: significance in special therapy.

PMID- 10070808
TI  - Fibrinogen as a marker of inflammation: a clinical view.

PMID- 10070809
TI  - Fibrinogen and infection.

PMID- 10070810
TI  - Inflammation, atherosclerosis, and cardiovascular risk: an epidemiologic view.
AB  - Based on laboratory and experimental evidence, it has been hypothesized that
      inflammation plays a fundamental role in atherogenesis and acute thrombosis. From
      an epidemiologic perspective, corroboration of this hypothesis has been provided
      by a series of prospective cohort studies which demonstrate that inflammatory
      parameters (such as fibrinogen, C reactive protein, and serum amyloid A),
      cellular adhesion molecules [such as intercellular adhesion molecule (ICAM)-1],
      and cytokines (such as interleukin-6) are all elevated at baseline among patients
      at risk for future coronary occlusion. Furthermore, data deriving from randomized
      clinical trials suggest that the efficacy of common preventive agents such as
      aspirin and hydroxy-methylglutaryl (HMG) CoA reductase inhibition may derive in
      part from interactions with the inflammatory system. Taken together, these data
      raise the possibility that therapies targeting chronic low-grade inflammation may
      provide novel future strategies for cardiovascular disease prevention.

PMID- 10070811
TI  - Fibrinogen and cardiovascular risk markers.

PMID- 10070812
TI  - Gene-environment interaction in the determination of levels of haemostatic
      variables involved in thrombosis and fibrinolysis.
AB  - Although a specific genotype may be associated in healthy subjects with modest
      differences in levels of a risk factor for thrombosis, this effect may be larger
      or smaller in subgroups of subjects. Documenting such gene-environment
      interactions is important if genotype information is ever to be used in a
      clinical or diagnostic setting, and understanding the molecular mechanisms of
      such interactions is vital to be able to use the information to develop novel
      therapeutic approaches for reducing the risk of myocardial infarction. This
      review focuses on gene-environment interactions detected to date for the G-455A
      beta fibrinogen gene promoter polymorphism. Carriers of the A allele,
      representing roughly 20% of the population, consistently have on average 7-10%
      higher fibrinogen levels than those with the genotype GG. Data will be presented
      to demonstrate interaction between gender, smoking habit, age, presence of
      ischaemic disease and level of physical exercise, in the determination of the
      magnitude of this A-raising effect and thus on an individual's plasma fibrinogen
      levels.

PMID- 10070813
TI  - Genetic prediction of myocardial infarction.

PMID- 10070814
TI  - Fibrinogen, obesity and insulin resistance.

PMID- 10070815
TI  - Should fibrinogen be measured routinely in patients with unstable coronary heart
      disease?

PMID- 10070816
TI  - Plasma gamma'/gamma fibrinogen ratio, a marker of arterial thrombotic activity: a
      new potential cardiovascular risk factor?

PMID- 10070817
TI  - Lowering fibrinogen levels: clinical update. BIP Study Group. Bezafibrate
      Infarction Prevention.
AB  - The preliminary conclusions from the BIP Study on the issue of fibrinogen are:
      (1) baseline fibrinogen was associated with age, gender, behavioral variables,
      lipid profile and severity of coronary heart disease. Furthermore, baseline
      fibrinogen emerged as an independent predictor of cardiovascular events in
      patients with coronary artery disease; (2) reduction of fibrinogen was not
      associated with a decrease in cardiac events in patients with coronary artery
      disease; (3) however, in patients with high baseline fibrinogen levels, reduction
      of fibrinogen was associated with a decrease in the incidence of primary
      endpoints, cardiac death and ischemic stroke. Further analysis from the BIP Study
      and additional data from other studies are necessary in order to clarify the
      possible association between fibrinogen alteration and cardiovascular events.

PMID- 10070818
TI  - Fibrinogen and fibrin polymerization and functions.

PMID- 10070819
TI  - Pharmacological remodeling of the thrombus architecture.

PMID- 10070820
TI  - Is thrombin a pharmacological target during reperfusion?

PMID- 10070821
TI  - Fibrin-fibrinogen and dethrombosis.

PMID- 10070822
TI  - Platelet glycoprotein polymorphism and risk for coronary heart disease.

PMID- 10070823
TI  - Different activation states of GP IIb/IIIa complexes in platelets.

PMID- 10070824
TI  - IIb/IIIa inhibitors in acute myocardial infarction.
AB  - Platelets play a key role both in ischemic complications after percutaneous
      transluminal coronary angioplasty (PTCA) and in the pathogenesis of acute
      myocardial infarction (AMI). Until recently, there was no treatment to dissolve
      the platelet clot. Indeed, the plasminogen activators achieve fibrin lysis but
      their platelet activating side-effects and their prothrombotic effects led to
      failure in PTCA trials and to a significant rate of reocclusions in thrombolysis
      trials. A new class of platelet antagonists directed against the platelet
      membrane glycoprotein IIb/IIIa receptor has undergone extensive evaluation in the
      prevention of ischemic complications of PTCA. In contrast, its development in the
      treatment of AMI is just starting. This class of medications has the potential to
      improve clinical outcome of AMI treated either with primary angioplasty or with
      thrombolysis.

PMID- 10070825
TI  - Fibrinogen receptor and platelet signalling.

PMID- 10070826
TI  - Monitoring platelet GPIIb/IIIa antagonist therapy.

PMID- 10070827
TI  - Clinical benefit of fibrinogen evaluation.

PMID- 10070828
TI  - Abstracts presented to the Fourth International Fibrinogen Symposium.

PMID- 10070829
TI  - Familial thrombophilia and the prothrombin 20210A mutation: association with
      increased thrombin generation and unusual thrombosis.
AB  - The 20210A prothrombin mutation has recently been associated with an increased
      risk of venous thrombosis, but the mechanism of the increased thrombotic risk in
      affected persons has not been elucidated. We report on a thrombophilic family in
      which the proband presented with cerebral vein thrombosis and homozygosity for
      the 20210A prothrombin mutation as her only identifiable risk factor for venous
      thrombosis. Extended genotyping of family members revealed seven other affected,
      but asymptomatic, first-degree relatives (one A/A homozygote and six G/A
      heterozygotes). Plasma levels of prothrombin, prothrombin fragments 1 + 2 and
      thrombin-antithrombin complexes were highest in A/A homozygotes, intermediate in
      G/A heterozygotes and lowest in those with the G/G homozygous normal genotype,
      while D-dimer levels were elevated only in A/A homozygotes. Our results suggest
      that the 20210A prothrombin mutation is associated with activation of coagulation
      and increased thrombin generation, not only in patients with a past history of
      thrombosis but also in otherwise healthy asymptomatic persons. In a similar
      fashion to the homozygous factor V Leiden mutation, patients with the homozygous
      20210A prothrombin mutation could be at highest risk of thrombosis, as suggested
      by our patient who presented with unusual thrombosis.

PMID- 10070830
TI  - Careful selection of sample dilution and factor-V-deficient plasma makes the
      modified activated protein C resistance test highly specific for the factor V
      Leiden mutation.
AB  - The aim of this study was to evaluate critically the recently modified activated
      partial-thromboplastin-time (APTT)-based activated protein C (APC)-resistance
      tests, which are more specific for the factor V Leiden mutation than the first
      generation APC-resistance tests. The only modification to these tests is the
      predilution of the plasma sample in factor-V-deficient plasma. The intended
      effect of this predilution is to bring the concentrations of all clotting
      factors, except factor V, to the same normal levels. This, in principle, makes
      the tests also suitable for assaying the plasma of patients treated with oral
      anticoagulants and heparin, or of patients with a lupus anticoagulant. However,
      not every factor-V-deficient plasma is suitable for this application. Because the
      factor V:factor VIII ratio is important in establishing the APC ratio, the factor
      V-deficient plasma should contain a sufficiently high factor VIII concentration.
      We also found that the optimal dilution to obtain the same APC ratios for
      patients, whether or not treated with coumarins or heparin, is not the same for
      each test or factor-V-deficient plasma. We compared two modified APTT-based APC
      resistance tests (one developed in our laboratory and one commercial) with
      respect to their ability to discriminate between carriers and non-carriers of the
      factor V Leiden mutation. Both modified tests gave complete separation of
      carriers and non-carriers of the factor V Leiden mutation whether or not they are
      treated with anticoagulants. This makes these tests very suitable for routine
      screening.

PMID- 10070831
TI  - Acute effects of angiotensin II on fibrinolysis in healthy volunteers.
AB  - Recent studies have suggested that angiotensin II may inhibit fibrinolysis. In
      order to further test this hypothesis, we investigated the acute effects of
      angiotensin II (intravenous infusion of 10 ng/kg per min over 15-20 min) on
      fibrinolytic function in 18 healthy men. Time-controls (n=11) and control
      experiments with a placebo infusion (n = 13) were also performed. The activities
      of plasmin activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t
      PA), as well as t-PA antigen levels, were determined in plasma before, during and
      60 min after the infusion of angiotensin II. Angiotensin II caused a clear-cut
      elevation in blood pressure; heart rate and plasma noradrenaline levels tended to
      decrease during the infusion but increased afterwards, indicating reflexogenic
      adjustments. Plasma t-PA activity and antigen levels increased by 81+/-11 and
      14+/-3%, respectively, during angiotensin II infusion (both P < 0.001), whereas t
      PA activity was unchanged and t-PA antigen decreased (P < 0.05) in placebo
      experiments. PAI-1 activity decreased similarly in time-controls and during
      angiotensin infusion (P < 0.001). Thus, short-term infusion of angiotensin II
      enhances fibrinolysis by elevating plasma t-PA. It is not clear whether this is a
      direct angiotensin-receptor-mediated effect or if it is related to the
      hemodynamic effects of the infusion.

PMID- 10070832
TI  - Performance of the platelet function analyser PFA-100 in testing abnormalities of
      primary haemostasis.
AB  - The PFA-100 device is a new instrument for the in-vitro testing of platelet
      function. Primary haemostasis is stimulated by recording the closure time taken
      for platelets to seal a 150 microm aperture in the centre of a membrane coated
      with collagen and either epinephrine or ADP. Patients with type 3 von
      Willebrand's disease (n = 4) all had infinitely prolonged closure times (> 200 s)
      with both types of cartridge. A patient with afibrinogenemia exhibited only
      slightly prolonged closure times of 111 and 166 s for the ADP and epinephrine
      membranes, respectively. Patients with Glanzmann's thrombasthenia (n = 6) and
      Bernard Soulier syndrome (n = 2) had grossly prolonged closure times (> 200 s)
      with both types of cartridges. These results confirmed that the PFA-100 system
      was highly dependent on normal von Willebrand factor, glycoprotein Ib and
      glycoprotein IIb/IIIa levels but not on plasma fibrinogen. Patients with storage
      pool disease (n = 6) and Hermansky Pudlak syndrome (n = 7) had prolonged closure
      times with the epinephrine cartridge. There was no evidence of enhanced platelet
      function in patients with antiphospholipid syndrome, in sickle-cell disease or
      thalassemia. However, ingestion of aspirin resulted in a near consistent and
      significant prolongation of the closure time for the epinephrine cartridge but
      not for the ADP cartridge in both normal subjects and patients. The test offers a
      reliable, reproducible, rapid and simple means of assessing high-shear platelet
      function in vitro.

PMID- 10070833
TI  - Treatment with recombinant activated factor VII in a patient with hemophilia A
      and an inhibitor: advantages of administration by continuous infusion over bolus
      intermittent injections.
AB  - Recent studies have shown that treatment with a continuous infusion of
      recombinant activated factor VII (rFVIIa) is far more convenient than
      administration by bolus intermittent injections and may allow a substantial
      reduction in the dose. We present the case of a 26-year-old patient with
      hemophilia A, who had a high-titer inhibitor to both human and porcine factor
      VIII, and who had recently been admitted to hospital because of a bilateral
      severe ilio-psoas hematoma. Two subsequent courses of treatment with rFVIIa by
      bolus intermittent injection showed only a partial efficacy. A further
      administration of rFVIIa was therefore carried out using a continuous infusion
      regimen that proved to be fully efficacious. During the continuous infusion
      course levels of factor VII coagulant activity were in the range 18.2-5.2 U/ml,
      while the prothrombin time, expressed as an International Normalized Ratio,
      remained within the range 0.57-0.71. The continuous infusion, compared with the
      administration of the bolus intermittent infusion, reduced the amount of rFVIIa
      required by approximately 40-50%. Statistical analysis demonstrated that there
      was a strong positive correlation between the rate of infusion of rFVIIa and
      levels of factor VII coagulant activity (r = +0.941; P < 0.001), and a very
      significant negative correlation between levels of factor VII coagulant activity
      and prothrombin time values (r = -0.897; P < 0.001). In accordance with previous
      findings, our experience confirms that, when prolonged therapy is required,
      treatment with rFVIIa by continuous infusion is more convenient than
      administration of bolus intermittent injections, and may allow the saving of a
      large amount of drug. Moreover, we suggest potential additional advantages of the
      continuous infusion regimen over bolus intermittent injections, such as a better
      efficacy and a stronger correlation between prothrombin time and factor VII
      coagulant activity levels.

PMID- 10070834
TI  - The prothrombin 20210A allele and the factor V Leiden are associated with venous
      thrombosis but not with early coronary artery disease.
AB  - This study was performed in order to establish the role of the prothrombin 20210
      G/A and factor V Leiden (R506Q) polymorphisms in the susceptibility to develop
      venous thromboembolism and early coronary artery disease (CAD). These
      polymorphisms were determined in 82 consecutive patients with venous
      thromboembolism, 175 male patients with early CAD, and 200 healthy controls from
      the same Caucasian population (Asturias, Northern Spain). DNA was amplified using
      polymerase chain reactions and digested with the appropriate restriction enzymes
      in order to define the prothrombin and factor V genotypes. The prevalence of the
      heterozygous for the prothrombin A allele was 3.5% in the general population and
      15.8% in patients with venous thrombosis (P = 0.0007); the frequency was 4% in
      patients with early CAD. No sex-related differences in the prevalence of the A
      allele were observed, and the average age at the first venous thromboembolic
      event was similar between GG and AG patients. The frequency of carriers of the
      factor V Leiden polymorphism was 9.75% among patients with venous
      thromboembolism, compared with 3.5% among controls, and 3.4% in the patients with
      CAD. Our data showed an association between venous thromboembolism and the AG
      genotype at the prothrombin 20210 G/A polymorphism. This polymorphism was not
      related to an increased risk for early CAD in our population of male patients.

PMID- 10070835
TI  - Evaluation of left ventricular wall motion, volumes, and ejection fraction by
      gated myocardial tomography with technetium 99m-labeled tetrofosmin: a comparison
      with cine magnetic resonance imaging.
AB  - BACKGROUND: Whether left ventricular function can be assessed accurately by gated
      single photon emission computed tomography (SPECT) in patients with myocardial
      infarction and severe perfusion defects is not well known. METHODS AND RESULTS:
      Twenty-five patients with an acute myocardial infarction underwent 99mTc-labeled
      tetrofosmin (99mTc-tetrofosmin) gated SPECT and cine magnetic resonance imaging
      (MRI). Wall motion was assessed in 13 left ventricular segments using a 5-point
      scoring system ranging from 3 (normal) to -1 (dyskinetic). Exact agreement for
      wall motion scores between gated SPECT and MRI was excellent (92%, kappa = 0.82).
      Furthermore, correlations between the two techniques were also good for end
      diastolic volume (r = 0.81, P < .0001), end-systolic volume (r = 0.92, P <
      .0001), and ejection fraction (r = 0.93, P < .0001). CONCLUSION: In patients with
      a recent myocardial infarction, 99mTc-tetrofosmin gated SPECT provides reliable
      evaluation of global and regional ventricular function and volumes.

PMID- 10070836
TI  - Myocardial blood flow and perfusion reserve in infarcted patients with stress
      induced normalization of previously negative T waves: a positron emission
      tomography study.
AB  - BACKGROUND: The clinical correlations between stress-induced normalization of
      previously negative T waves (NTW) and regional myocardial blood flow (MBF)
      regulation and tissue viability remain debatable. METHODS AND RESULTS: To confirm
      these correlations, 14 patients with previous anterior myocardial infarction (13
      Q waves) and NTW on baseline electrocardiographic precordial leads and 10 healthy
      subjects were studied by means of positron emission tomography (PET). The MBF
      values were obtained in the anterior infarcted myocardial regions in either
      resting condition or during dipyridamole infusion, using N-13 ammonia as a flow
      tracer. Seven subjects had normalization of NTW (Group 1) and 7 had persistent
      NTW (Group 2) during dipyridamole infusion. The resting MBF values were similar
      for both Group 1 and Group 2 (0.43+/-0.13 versus 0.51+/-0.15 mL.min(-1).g(-1),
      respectively; P = not significant) and were significantly lower than in the
      anterior myocardial regions of healthy subjects (1.03+/-0.23 mL.min(-1).g(-1), P
      < .001). After administration of dipyridamole, the MBF was significantly higher
      in Group 1 than in Group 2 (0.88 +/- 0.37 versus 0.55 +/- 0.17 mL.min(-1).g(-1),
      respectively; P < .05) and markedly lower than in healthy subjects (3.78+/-0.64
      mL.min(-1).g(-1), P < .001). Coronary reserves (dipyridamole/resting MBF) were
      2.03+/-0.40 and 1.14+/-0.44 in Group 1 and Group 2, respectively (P < .002).
      CONCLUSION: Despite similar values of resting perfusion, infarcted dysfunctional
      areas with or without NTW during stress may present different regional MBF
      responses; normalization of NTW demonstrates higher coronary flow reserve than
      persistent NTW, suggesting a better preserved coronary microcirculatory function
      in the former, indicative of the presence of myocardial viability.

PMID- 10070837
TI  - Development of respiratory gated myocardial SPECT system.
AB  - BACKGROUND: The superposition of the diaphragm and abdominal structures on the
      inferior wall of the left ventricle has often distorted single photon emission
      computed tomography (SPECT). We developed a respiratory gated SPECT (RGS) system
      to diminish artifacts caused by overlap between the inferior wall and upper
      abdomen and have validated its feasibility for clinical use. METHODS AND RESULTS:
      A 2-detector SPECT system equipped with a respiratory monitor based on impedance
      plethysmography and an original triggering apparatus was used for RGS in 7
      healthy male volunteers. A pulse triggered 100 ms after every expiratory peak was
      processed in a SPECT system as well as an electrocardiogram (ECG) gating pulse.
      Inspiratory and expiratory frames were determined using the respiratory curve
      derived from fluctuation of the gall bladder uptake. Both sets of images were
      reoriented into short-axis and vertical long-axis slices. For quantification,
      data were reconstructed into polar plots and count density estimated in 9
      myocardial segments. The mean percentage uptake of inferior segments at
      inspiration was significantly greater than that at expiration (81+/-8.3 versus
      76+/-7.1; P < .0001). The inferior-lateral activity ratio improved from 0.78 at
      expiration to 0.81 at inspiration (P < .01). The coefficient of variance for each
      segment of inspiratory data was significantly smaller than that at expiration,
      indicating improved homogeneity of tracer distribution. The lowest cutoff
      threshold of the tomograms to separate the inferior uptake from that of the upper
      abdomen was significantly lower at inspiration than at expiration, suggesting
      smaller scatter from abdominal structures on inspiratory images. CONCLUSIONS: RGS
      yielded improved tracer uptake of the inferior wall in healthy male subjects and
      may be suitable as an alternative method for attenuation and scatter correction.
      However, further clinical validation is needed.

PMID- 10070838
TI  - Effects of smoking on pulmonary uptake of technetium-99m
      methoxyisobutylisonitrile during myocardial perfusion imaging.
AB  - BACKGROUND: To determine the influence of smoking on 99mTc-labeled
      methoxyisobutylisonitrile (99mTc-MIBI) lung uptake during myocardial perfusion
      imaging, we examined 60 subjects with normal myocardial perfusion scans, normal
      coronary angiograms, and no evidence of left ventricular hypertrophy. METHODS AND
      RESULTS: The subjects were divided into 2 groups: Group 1 subjects had smoking
      histories of at least 10 pack-years and Group 2 subjects were nonsmokers. 99mTc
      MIBI lung to heart ratios (L/H ratios) from anterior planar images were obtained
      for all subjects during exercise and resting states. 99mTc-MIBI L/H ratios in
      smokers were significantly higher than in nonsmokers in both exercise and resting
      states. However, no significant difference in L/H ratios was found between
      exercise and resting states in smokers and nonsmokers. In addition, no
      significant correlation was found between smoking pack-years and either rest or
      exercise L/H ratios. CONCLUSIONS: 99mTc-MIBI L/H ratios in smokers are higher
      than in nonsmokers. This must be considered when 99mTc-MIBI L/H ratios are used
      clinically.

PMID- 10070839
TI  - Assessment of myocardial fatty acid metabolism in atrioventricular synchronous
      pacing: analysis of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid
      SPECT.
AB  - BACKGROUND: We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) single
      photon emission computed tomography (SPECT) to evaluate fatty acid metabolism in
      patients who were candidates for permanent pacemaker implantation and in patients
      with atrioventricular (AV) synchronous pacing. METHODS AND RESULTS: We performed
      BMIPP SPECT studies in 66 patients with bradyarrhythmia, of whom 11 patients were
      candidates for permanent pacemaker implantation, 27 patients had atrial pacing
      (atrial sensing, inhibited mode, simple programmable [AAI]), and 28 patients had
      atrial synchronous ventricular inhibited pacing (ventricular pacing, 2-chamber
      sensing, atrial-triggered and ventricular-inhibited, multiprogrammable [VDD]) or
      atrial and ventricular pacing in sequence (atrial and ventricular sensing, atrial
      inhibited and atrial-triggered, ventricular-inhibited, multiprogrammable [DDD]).
      A qualitative assessment revealed that the BMIPP uptake at the septal, inferior,
      and apical regions was significantly decreased in the patients with VDD/DDD
      compared with both the candidates for permanent pacemaker implantation and the
      patients with AAI. The total extent score (ES) and severity score (SS) were
      significantly higher in the patients with VDD/DDD than in the other 2 groups.
      Significant regional differences of both ES and SS values were observed at the
      septal and inferior regions in the patients with VDD/DDD compared with the other
      groups. No differences were found between the qualitative and quantitative
      measures of BMIPP uptake in the candidates for permanent pacemaker implantation
      and those in the patients with AAI. CONCLUSION: Our study suggests that AV
      synchronous right ventricular pacing resulting in the delayed conduction and
      depolarization of myocardial cells may directly interfere with regional cellular
      free fatty acid uptake and metabolism.

PMID- 10070840
TI  - Radiolabeled MDA2, an oxidation-specific, monoclonal antibody, identifies native
      atherosclerotic lesions in vivo.
AB  - BACKGROUND: Oxidatively modified low-density lipoprotein (LDL) is present in
      atherosclerotic but not normal arteries and plays a crucial role in the
      pathogenesis and adverse consequences of atherosclerotic lesions. We previously
      generated a series of monoclonal antibodies (MoAb) against oxidation-specific neo
      epitopes formed during the oxidative modification of LDL. MDA2, a prototype MoAb,
      recognizes malondialdehyde-lysine epitopes (eg, in malondi-aldehyde-modified LDL)
      within atherosclerotic lesions. We describe the in vivo characteristics of MDA2
      and initial noninvasive imaging studies of atherosclerosis in rabbits. METHODS:
      To assess the in vivo specificity of MDA2 for atherosclerotic lesions, iodine 125
      MDA2 was intravenously injected into 7 LDL-receptor deficient Watanabe heritable
      hyperlipidemic (WHHL) and 2 normal New Zealand white (NZW) rabbits, and the
      aortic plaque uptake was evaluated 24 hours later. 125I-Halb, an isotype-matched
      irrelevant MoAb that binds to human albumin, was injected into 5 WHHL and 2 NZW
      rabbits as a control. Aortic autoradiography was performed, and the mean uptake
      of MoAbs was measured as the percent injected dose per gram aortic tissue. Gamma
      camera imaging was then carried out in 7 WHHL rabbits and 2 NZW rabbits with
      99mTc-MDA2. Imaging was carried out at 10 minutes and at 12 or 24 hours.
      Malondialdehyde-LDL was then injected to clear the blood pool signal, and final
      images were obtained 2 hours later. RESULTS: Mean uptake of 125I-MDA2 in the
      entire aorta was 17.4-fold higher in WHHL than in NZW aortas (P < .001), and 2.8
      fold higher than 125I-Halb in WHHL aortas. 125I-MDA2 also had higher specificity
      for lesioned areas than 125I-Halb (plaque/normal ratio 6.3 vs 2.9, P < .001).
      Autoradiograph of aortas of 125I-MDA2-injected WHHL rabbits revealed uptake in
      lipid-stained lesions with absence of signal in adjacent normal arterial tissue.
      Immunostaining of WHHL lesions, which accumulated MDA2 as noted on
      autoradiography, revealed that uptake was highest in areas with abundant foam
      cells and in lipid-rich necrotic core areas. Autoradiograph of aortas from NZW
      rabbits injected with 125I-MDA2 did not yield any visible signal. Planar gamma
      camera in vivo scintigraphy revealed a visible signal in 4/7 WHHL rabbits, which
      was confirmed by aortic Sudan staining. CONCLUSION: Radiolabeled MDA2 shows
      excellent in vivo uptake and specificity for atherosclerotic lesions containing
      abundant oxidation-specific epitopes. The in vivo imaging studies suggest that
      noninvasive imaging of oxidation-rich atherosclerotic lesions with radiolabeled
      MDA2 may be feasible in human beings with optimization of the imaging methods.

PMID- 10070842
TI  - Gene therapy for cardiovascular diseases.

PMID- 10070841
TI  - Clinical review of attenuation-corrected cardiac SPECT.
AB  - Rather than the introduction of a heralded technologic advancement in cardiac
      SPECT imaging challenging the accuracy of PET perfusion imaging, the commercial
      introduction of attenuation correction has been met with at least as many
      negative as positive reports. Some studies have reported significant improvements
      in specificity or specificity and sensitivity, especially for high-risk patterns
      of coronary artery disease; others have reported no improvement or a decrease in
      accuracy resulting from the introduction of troublesome artifacts. Although this
      review has attempted to emphasize the positive aspects of attenuation-corrected
      cardiac SPECT perfusion imaging and the potential for improved patient care it
      may provide, several negative reports continue to appear. Still there has been
      sufficient positive data reported to suggest that with fully developed, accurate,
      and robust correction methods, significant gains in SPECT assessments of the
      presence and extent of CHD, patient risk, and myocardial viability can be
      anticipated. Ultimately attenuation correction for cardiac SPECT should have a
      positive impact on the management of patients with coronary artery disease with
      important savings in lives and health care dollars.

PMID- 10070843
TI  - Government relations for technologists: "what's up doc?".

PMID- 10070844
TI  - Strategic targeting of atherosclerotic lesions.

PMID- 10070845
TI  - Scleroderma heart disease: an unusual cause of positive antimyosin cardiac
      imaging.
AB  - In-antimyosin scintigraphy offers a valuable noninvasive method for early
      detection of clinically silent cardiac involvement in patients with systemic
      sclerosis, even in the absence of left ventricular dysfunction. In these patients
      with positive antimyosin study results, intense pharmacologic treatment with
      vasodilators may be warranted.

PMID- 10070853
TI  - Nuclear cardiology in the literature.

PMID- 10070854
TI  - Stress test reporting.

PMID- 10070855
TI  - 'Should a mammographic screening programme carry the warning: screening can
      damage your health!'?
AB  - The balanced presentation afforded by convening a Citizens' Jury when considering
      a major question such as the introduction of a breast screening programme is
      advocated. This method would enable account to be taken of all the costs, both
      human and financial, to all those affected, both participating and organizing, as
      well as the benefits. Provision of such a democratic opportunity enables
      consideration to be given to a broad range of factors, by selection of an
      appropriate range of witnesses, with the advantage of involving the lay public in
      this decision-making process. Attendance by health correspondents, medical
      journalists and other media representatives enables publicization of a democracy
      in action whilst helping to inform the wider debate. Such an exercise could
      inform whether the NHS BSP should continue in its current form.

PMID- 10070856
TI  - Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast
      cancer cell line.
AB  - The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF
      1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxifen-resistant
      (MCF 7/5-23) subclones of the MCF 7 cell line. Both subclones were grown in
      defined, serum-free (SF) medium over a period of 7 days with the addition of E2
      or IGF-1 or a combination of both agents. Growth of both MCF 7/5-21 and 7/5-23
      cells was stimulated (245% and 350%, respectively) by E2. However, only the
      growth of MCF 7/5-23 cells was stimulated (266%) by IGF-1. A combination of E2
      and IGF-1 significantly enhanced MCF 7/5-21 and 7/5-23 cell growth (581% and
      695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by
      125I-IGF-1 binding and Northern analyses) in only MCF 7/5-23 cells. This effect
      was partially inhibited by tamoxifen. In medium containing serum, the growth of
      only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal
      antibody, alphaIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR
      was demonstrated in the MCF 7/5-23 cells. These experiments indicate that E2 may
      sensitize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions
      of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism
      that may manifest itself as tamoxifen resistance.

PMID- 10070857
TI  - Activation of integrin and ceramide signalling pathways can inhibit the mitogenic
      effect of insulin-like growth factor I (IGF-I) in human breast cancer cell lines.
AB  - Cell counting, cell cycle analysis and Western immunoblotting were used to
      examine the effects of non-apoptotic doses of a ceramide analogue, C2, and a
      synthetic arginine-glycine-aspartic acid (RGD)-containing peptide, RGD, in MCF-7
      and T47D cells to determine whether activation of these signalling pathways could
      alter the mitogenic potential of insulin-like growth factor I (IGF-I). IGF-I
      alone increased total cell number in both cell lines, associated with a rise in
      the percentage of cells in the S-phase of the cell cycle and a co-incident
      increase in cyclin A production. Treatments alone had no effects on cell number
      or cyclin A production relative to controls. C2 inhibited IGF-I-induced
      mitogenesis in both lines, whereas RGD was only effective in the T47D line.
      Despite inhibition of cell proliferation, IGF-I stimulation of cells in S-phase
      and of cyclin A levels were unaffected; however, an IGF-I-induced increase in
      cyclin B1 levels was inhibited by 30%. Low-dose induction of integrin and
      ceramide signalling pathways causes cells to be blocked in S-phase, thereby
      inhibiting the normal cycle of events associated with the IGF-I-induced mitotic
      signal. Activating these pathways may not only restrict tumour growth by
      induction of apoptosis but they may also directly inhibit IGF-I-induced cell
      proliferation.

PMID- 10070858
TI  - Isolation and characterization of a new human breast cancer cell line, KPL-4,
      expressing the Erb B family receptors and interleukin-6.
AB  - A new human breast cancer cell line, KPL-4, was recently isolated from the
      malignant pleural effusion of a breast cancer patient with an inflammatory skin
      metastasis. This cell line can be cultured under serum-free conditions and is
      tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the
      expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold
      amplification of the erb B-2. Reverse transcription-polymerase chain reaction
      analysis showed a detectable level of mRNA expression of all the Erb B family
      receptors. In addition, all the receptors were autophosphorylated under a serum
      supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia
      of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in
      both the culture medium and the serum of mice. The weight of tumours
      significantly correlated with the serum IL-6 level. The antiproliferative effect
      of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated.
      This antibody significantly inhibited the growth of KPL-4 cells in vitro but
      modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2.
      These findings suggest that KPL-4 cells may be useful in the development of new
      strategies against breast cancer overexpressing the Erb B family receptors and
      against IL-6-induced cachexia.

PMID- 10070859
TI  - Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic
      breast carcinoma.
AB  - We examined a panel of sporadic breast carcinomas for loss of heterozygosity
      (LOH) in a 10-cM interval on chromosome 10 known to encompass the PTEN gene. We
      detected allele loss in 27 of 70 breast tumour DNAs. Fifteen of these showed loss
      limited to a subregion of the area studied. The most commonly deleted region was
      flanked by D10S215 and D10S541 and encompasses the PTEN locus. We used a
      combination of denaturing gradient gel electrophoresis and single-strand
      conformation polymorphism analyses to investigate the presence of PTEN mutations
      in tumours with LOH in this region. We did not detect mutations of PTEN in any of
      these tumours. Our data show that, in sporadic breast carcinoma, loss of
      heterozygosity of the PTEN locus is frequent, but mutation of PTEN is not. These
      results are consistent with loss of another unidentified tumour suppressor in
      this region in sporadic breast carcinoma.

PMID- 10070860
TI  - Genetic aberrations in glioblastoma multiforme: translocation of chromosome 10 in
      an O-2A-like cell line.
AB  - We have examined the genetic aberrations in two near-diploid glioblastoma
      multiforme cell lines that appear to have arisen from different glial lineages.
      One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles
      characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat
      central nervous system. This line generates, in vitro, cells with characteristics
      of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line,
      IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic
      differentiation. In Hu-O-2A/Gb1 the sole homologue of chromosome 10 is disrupted
      at band 10p11-12.1 by translocation with chromosomes X and 15. The translocation
      breakpoint is localized between genetic markers D10S2103 and [D10S637, D10S1962,
      D10S355]. Other aberrations include a 5;14 translocation, deletion of the long
      and short arms of chromosome 16 and loss of one copy of the CDKN2 gene. IN1434
      cells share some cytogenetic abnormalities with Hu-O-2A/Gb1 cells, despite their
      apparent derivation from a different biological origin, but also have
      translocations involving the long and short arms of chromosome 1 and the long arm
      of chromosome 7, and deletion of chromosome 13 at bands 13q12-21.

PMID- 10070861
TI  - Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric
      carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
AB  - The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium
      chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N
      nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of
      transforming growth factor (TGF) alpha in the gastric cancers was investigated in
      Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow
      pellets containing 10% sodium chloride and subcutaneous injections of RA at doses
      of 0.75 or 1.5 mg kg(-1) body weight every other day. In week 52, oral
      supplementation with sodium chloride significantly increased the incidence of
      gastric cancers compared with the untreated controls. Long-term administration of
      RA at both doses significantly reduced the incidence of gastric cancers, which
      was enhanced by oral administration of sodium chloride. RA at both doses
      significantly decreased the labelling index and TGF-alpha immunoreactivity of
      gastric cancers, which were enhanced by administration of sodium chloride, and
      significantly increased the apoptotic index of cancers, which was lowered by
      administration of sodium chloride. These findings suggest that RA attenuates
      gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis,
      decreasing DNA synthesis, and reducing TGF-alpha expression in gastric cancers.

PMID- 10070862
TI  - Induction of reactive oxygen intermediates in human monocytes by tumour cells and
      their role in spontaneous monocyte cytotoxicity.
AB  - The present study examined the ability of human monocytes to produce reactive
      oxygen intermediates after a contact with tumour cells. Monocytes generated
      oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide
      anion production, after stimulation with the tumour, but not with untransformed,
      cells. The use of specific oxygen radical scavengers and inhibitors, superoxide
      dismutase, catalase, dimethyl sulphoxide and deferoxamine as well as the
      myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide, indicated that
      chemiluminescence was dependent on the production of superoxide anion and
      hydroxyl radical and the presence of myeloperoxidase. The tumour cell-induced
      chemiluminescent response of monocytes showed different kinetics from that seen
      after activation of monocytes with phorbol ester. These results indicate that
      human monocytes can be directly stimulated by tumour cells for reactive oxygen
      intermediate production. Spontaneous monocyte-mediated cytotoxicity towards
      cancer cells was inhibited by superoxide dismutase, catalase, deferoxamine and
      hydrazide, implicating the role of superoxide anion, hydrogen peroxide, hydroxyl
      radical and hypohalite. We wish to suggest that so-called 'spontaneous'
      tumoricidal capacity of freshly isolated human monocytes may in fact be an
      inducible event associated with generation of reactive oxygen intermediates and
      perhaps other toxic mediators, resulting from a contact of monocytes with tumour
      cells.

PMID- 10070863
TI  - The contribution of DNA ploidy to radiation sensitivity in human tumour cell
      lines.
AB  - The contribution of DNA ploidy to radiation sensitivity was investigated in a
      group of eight human tumour cell lines. As previous studies suggest, while more
      aneuploid tumours tend to be more radioresistant, there is no significant
      relationship between ploidy and radiation sensitivity (SF2). The failure to
      observe a significant effect of ploidy on radiation sensitivity is due to the
      complex and multifactorial basis of radiation sensitivity. When we determined the
      relationship between survival and radiation-induced chromosome aberration
      frequency, a measure independent of most other modifiers of sensitivity, we
      observed a direct relationship between ploidy and mean lethal aberration
      frequency. The mean lethal frequency of aberrations increased from about 1 for
      diploid cells to about 2 for tetraploid cells. The mean lethal frequency of
      aberrations was independent of DNA repair variations. These observations
      demonstrate that changes in DNA ploidy are an important contributor to radiation
      sensitivity variations in human tumour cell lines. Therefore, any battery of
      predictive assays should include DNA ploidy measurements.

PMID- 10070864
TI  - DNA topoisomerase IIalpha and -beta expression in human ovarian cancer.
AB  - To study DNA topoisomerase IIalpha (Topo-IIalpha) and -beta expression and
      regulation in human ovarian cancer, 15 ovarian tumour samples were investigated.
      To compare different levels of expression, the samples were screened for topo
      IIalpha and -beta mRNA with Northern blotting and a quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) assay for Topo-IIalpha mRNA.
      Additionally, protein levels were determined with Western blotting and
      topoisomerase II activity levels with the decatenation assay. The results
      obtained were compared with each other and with the tumour volume index of the
      samples. In tumours with a tumour volume index > or = 50%, the mRNA levels (as
      determined by Northern blotting) and protein levels for each isozyme were in
      accordance. Additionally, correlations were found between Topo-IIalpha RT-PCR
      data and Topo-IIalpha Northern blot results, and between Topo-IIalpha RT-PCR data
      and Topo-IIalpha protein levels. Interestingly, Topo-IIbeta protein levels
      correlated better with Topo-II activity than Topo-IIalpha protein levels. In
      eight ovarian cystadenoma samples, no Topo-IIalpha protein could be found. In
      only three out of eight of these cystadenomas, Topo-IIbeta protein could be
      detected. These findings suggest that Topo-IIalpha and Topo-IIbeta protein levels
      are up-regulated in ovarian cancer and may indicate that Topo-IIbeta is an
      interesting target for chemotherapy in ovarian tumours.

PMID- 10070865
TI  - Exclusion of a major role for the PTEN tumour-suppressor gene in breast
      carcinomas.
AB  - PTEN is a novel tumour-suppressor gene located on chromosomal band 10q23.3. This
      region displays frequent loss of heterozygosity (LOH) in a variety of human
      neoplasms including breast carcinomas. The detection of PTEN mutations in Cowden
      disease and in breast carcinoma cell lines suggests that PTEN may be involved in
      mammary carcinogenesis. We here report a mutational analysis of tumour specimens
      from 103 primary breast carcinomas and constitutive DNA from 25 breast cancer
      families. The entire coding region of PTEN was screened by single-strand
      conformation polymorphism (SSCP) analysis and direct sequencing using intron
      based primers. No germline mutations could be identified in the breast cancer
      families and only one sporadic carcinoma carried a PTEN mutation at one allele.
      In addition, all sporadic tumours were analysed for homozygous deletions by
      differential polymerase chain reaction (PCR) and for allelic loss using the
      microsatellite markers D10S215, D10S564 and D10S573. No homozygous deletions were
      detected and only 10 out of 94 informative tumours showed allelic loss in the
      PTEN region. These results suggest that PTEN does not play a major role in breast
      cancer formation.

PMID- 10070866
TI  - Identification of a C/G polymorphism in the promoter region of the BRCA1 gene and
      its use as a marker for rapid detection of promoter deletions.
AB  - Reduced expression of BRCA1 has been implicated in sporadic breast cancer,
      although the mechanisms underlying this phenomenon remain unclear. To determine
      whether regulatory mutations could account for the reduced expression, we
      screened the promoter region by sequencing in 20 patients with sporadic disease.
      No mutations were detected; however, a new polymorphism consisting of a C-to-G
      base change within the beta-promoter was identified, with the frequency of the G
      allele being 0.34. Close to complete linkage disequilibrium was found between
      this marker and the Pro871 Leu polymorphism, situated in exon 11, which has
      previously been shown not to be associated with breast or ovarian cancer. This
      indicates that the C/G polymorphism is also unlikely to play a role in either
      disease. However, the strength of linkage disequilibrium between these markers
      permitted their use for rapid screening for genomic deletions within BRCA1. A
      series of 214 cases with familial breast cancer were analysed using this
      approach; 88/214 were heterozygous for the promoter polymorphism, thereby
      excluding a deletion in this region. Among the remaining patients, one hemizygous
      case reflecting a promoter deletion was successfully identified. Therefore, this
      study indicates that deletions within the beta-promoter region of BRCA1 are an
      uncommon event in familial breast cancer. Furthermore, it suggests that mutations
      within the BRCA1 promoter are unlikely to account for the reported decreased
      expression of BRCA1 in sporadic disease.

PMID- 10070867
TI  - Tumour inoculation site-dependent induction of cachexia in mice bearing colon 26
      carcinoma.
AB  - Murine colon 26 carcinoma growing at either subcutaneous (s.c.) or intramuscular
      (i.m.) inoculation sites causes cachexia in mice. Such animals show extensive
      loss of body weight, wasting of the muscle and adipose tissues, hypoglycaemia,
      and hypercalcaemia, even when the tumour weight comprises only about 1.9% of
      carcass weight. In contrast, the same tumour when inoculated into the liver does
      not cause any sign of tumour-related cachexia even when the tumour becomes much
      larger (6.6% of carcass weight). Interleukin 6 (IL-6), a mediator associated with
      cachexia in this tumour model, is detected at high levels both in the tumour
      tissues and in the circulating blood of mice bearing colon 26 tumour at the s.c.
      inoculation site. In contrast, only minute levels of IL-6 are detected in the
      tumour grown in the liver. The colon 26 tumour grown in the liver does not lose
      its ability to cause cachexia, because the tumour when re-inoculated s.c. is able
      to cause extensive weight loss and produce IL-6 as did the original colon 26 cell
      line. Histological studies revealed differences in the composition of tumour
      tissues: the tumours grown in the subcutis consist of many polygonal tumour
      cells, extended-intercellular space, and high vascular density, whereas those
      grown in the liver consist of spindle-shaped tumour cells. Thus, the environment
      where tumour cells grow would be a critical factor in determining the cachectic
      phenotype of cancer cells, including their ability to produce IL-6.

PMID- 10070868
TI  - Interleukin-2 gene transfer into human transitional cell carcinoma of the urinary
      bladder.
AB  - Transitional cell carcinoma of the bladder is one of the human cancers most
      responsive to immunotherapy, and local interleukin-2 (IL-2) production appears to
      be an important requirement for immunotherapy to be effective. In this study, we
      engineered two human bladder cancer cell lines (RT112 and EJ) to constitutively
      release human IL-2 by retroviral vector-mediated gene transfer. Following
      infection and selection, stable and consistent production of biologically active
      IL-2 was demonstrated at both the mRNA and the protein level. Morphology, in
      vitro growth rate and proliferation, as well as other cytokine gene mRNA or
      membrane adhesion receptor expression, were not altered in IL-2 transduced cells
      as compared to their parental or control vector-infected counterparts. Moreover,
      IL-2 engineered cells lost their tumorigenicity into nu/nu mice and the mechanism
      of rejection appeared to involve multiple host effector cell populations, among
      which a prominent role was played by neutrophils and radiosensitive cells. These
      findings may offer support to the development of an IL-2-based gene therapy
      approach to human bladder cancer.

PMID- 10070869
TI  - Blood flow influences vascular growth during tumour angiogenesis.
AB  - Many factors play a role in tumour angiogenesis. We observed growing tumour
      vessels in vivo to study the relationship between blood flow and vascular
      enlargement. Mammary adenocarcinoma was implanted into Fisher-344 rat with dorsal
      skin-fold transparent chambers. Vascular growth was observed and recorded on
      videotape through a microscope for 6 h. Vascular networks were photographed and
      traced every 30 min to identify changes over time. Tumour sections were stained
      with Masson's trichrome and anti-Factor VIII-related antigen. Tumour growth was
      rapid enough for differences to be seen each hour. Vessels with a high blood flow
      showed an increase in diameter within a few hours and new branches formed from
      these vessels. In contrast, vessels without an increase in blood flow showed no
      change in diameter. Vessels within the interstitium surrounding the tumour were
      lined by endothelium that was positive for anti-Factor VIII-related antigen
      staining. Vessels in the tumour had extremely rare endothelial cells detectable
      by Masson's trichrome or anti-Factor VIII-related antigen staining. In
      conclusion, increased blood flow may cause vascular enlargement and some
      primitive vessels seem to lack endothelium.

PMID- 10070870
TI  - Busulphan is active against neuroblastoma and medulloblastoma xenografts in
      athymic mice at clinically achievable plasma drug concentrations.
AB  - High-dose busulphan-containing chemotherapy regimens have shown high response
      rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and
      medulloblastoma. However, the anti-tumour activity of busulfan as a single agent
      remains to be defined, and this was evaluated in athymic mice bearing advanced
      stage subcutaneous paediatric solid tumour xenografts. Because busulphan is
      highly insoluble in water, the use of several vehicles for enteral and parenteral
      administration was first investigated in terms of pharmacokinetics and toxicity.
      The highest bioavailability was obtained with busulphan in DMSO administered i.p.
      When busulphan was suspended in carboxymethylcellulose and given orally or i.p.,
      the bioavailability was poor. Then, in the therapeutic experiments, busulphan in
      DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose
      (50 mg kg(-1)), busulphan induced a significant tumour growth delay, ranging from
      12 to 34 days in the three neuroblastomas evaluated and in one out of three
      medulloblastomas. At a dose level above the maximum tolerated dose, busulphan
      induced complete and partial tumour regressions. Busulphan was inactive in a
      peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan
      pharmacokinetics in mice and humans were considered, the estimated systemic
      exposure at the therapeutically active dose in mice (113 microg h ml(-1)) was
      close to the mean total systemic exposure in children receiving high-dose
      busulphan (102.4 microg h ml(-1)). In conclusion, busulphan displayed a
      significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts
      at plasma drug concentrations which can be achieved clinically in children
      receiving high-dose busulphan-containing regimens.

PMID- 10070871
TI  - Potentiation of anti-cancer drug activity at low intratumoral pH induced by the
      mitochondrial inhibitor m-iodobenzylguanidine (MIBG) and its analogue
      benzylguanidine (BG).
AB  - Tumour-selective acidification is of potential interest for enhanced therapeutic
      gain of pH sensitive drugs. In this study, we investigated the feasibility of a
      tumour-selective reduction of the extracellular and intracellular pH and their
      effect on the tumour response of selected anti-cancer drugs. In an in vitro L1210
      leukaemic cell model, we confirmed enhanced cytotoxicity of chlorambucil at low
      extracellular pH conditions. In contrast, the alkylating drugs melphalan and
      cisplatin, and bioreductive agents mitomycin C and its derivative EO9, required
      low intracellular pH conditions for enhanced activation. Furthermore, a strong
      and pH-independent synergism was observed between the pH-equilibrating drug
      nigericin and melphalan, of which the mechanism is unclear. In radiation-induced
      fibrosarcoma (RIF-1) tumour-bearing mice, the extracellular pH was reduced by the
      mitochondrial inhibitor m-iodobenzylguanidine (MIBG) or its analogue
      benzylguanidine (BG) plus glucose. To simultaneously reduce the intracellular pH,
      MIBG plus glucose were combined with the ionophore nigericin or the Na+/H+
      exchanger inhibitor amiloride and the Na+-dependent HCO3-/Cl- exchanger inhibitor
      4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). Biochemical studies
      confirmed an effective reduction of the extracellular pH to approximately 6.2,
      and anti-tumour responses to the interventions indicated a simultaneous reduction
      of the intracellular pH below 6.6 for at least 3 h. Combined reduction of extra-
      and intracellular tumour pH with melphalan increased the tumour regrowth time to
      200% of the pretreatment volume from 5.7 +/- 0.6 days for melphalan alone to 8.1
      +/- 0.7 days with pH manipulation (P < 0.05). Mitomycin C related tumour growth
      delay was enhanced by the combined interventions from 3.8 +/- 0.5 to 5.2 +/- 0.5
      days (P < 0.05), but only in tumours of relatively large sizes. The interventions
      were non-toxic alone or in combination with the anti-cancer drugs and did not
      affect melphalan biodistribution. In conclusion, we have developed non-toxic
      interventions for sustained and selective reduction of extra- and intracellular
      tumour pH which potentiated the tumour responses to selected anti-cancer drugs.

PMID- 10070872
TI  - Bioavailability and toxicity after oral administration of m-iodobenzylguanidine
      (MIBG).
AB  - meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for
      diagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocytoma
      and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v., is
      used in several clinical studies. These include palliation of the carcinoid
      syndrome, in which MIBG proved to be effective in 60% of the patients. Oral MIBG
      administration might be convenient to maintain palliation and possibly improve
      the percentage of responders. We have, therefore, investigated the feasibility of
      oral administration of MIBG in an animal model. Orally administered MIBG
      demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg(
      1). The first and only toxicity encountered was a decrease in renal function,
      measured by a reduced clearance of [51Cr]EDTA and accompanied by histological
      tubular damage. Repeated MIBG administration of 40 mg kg(-1) for 5 sequential
      days or of 20 mg kg(-1) for two courses of 5 sequential days with a 2-day
      interval did not affect renal clearance and was not accompanied by histological
      abnormalities in kidney, stomach, intestines, liver, heart, lungs, thymus,
      salivary glands and testes. Because of a sufficient bioavailability in absence of
      gastrointestinal toxicity, MIBG is considered suitable for further clinical
      investigation of repeated oral administration in patients.

PMID- 10070873
TI  - GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation
      therapy in rhabdomyosarcoma cells.
AB  - Differentiation therapy provides an alternative treatment of cancer that
      overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity
      and resistance to drugs. This new approach to cancer therapy focuses on the
      development of specific agents designed to selectively engage the process of
      terminal differentiation, leading to the elimination of tumorigenic cells and
      recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine
      acyclonucleoside-like compounds were designed and synthesized by structural
      modifications of 5-fluorouracil, a drug which causes considerable cell toxicity
      and morbidity, and we evaluated their applicability for differentiation therapy
      in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, (RS)
      1-[[3-(2-hydroxyethoxy)-1-isopropoxy]propyl]-5-fluorouracil, an active drug which
      shows low toxicity in vivo and releases acrolein which is an aldehyde with anti
      tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent
      growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses
      (22.5 micromol l(-1) and 45 micromol l(-1)) and induced terminal myogenic
      differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days.
      Changes in morphological features and in protein organization indicated re-entry
      in the pathway of muscular maturation. Moreover, GR-891 increased adhesion
      capability mediated by the expression of fibronectin, and did not induce
      overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug
      resistance. New acyclonucleoside-like compounds such as GR-891 have important
      potential advantages over 5-fluorouracil because of their lower toxicity and
      their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our
      results suggest that this drug may be useful for differentiation therapy in this
      type of tumour.

PMID- 10070874
TI  - RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII
      and SCCVII tumours in C3H mice.
AB  - Pre-clinical evaluation has demonstrated that 2-[4-(((3,5
      dimethylanilino)carbonyl)methyl)phenoxy]-2-methylpropi onic acid (RSR13) acts as
      an allosteric effector of haemoglobin (Hb). RSR13 binding to Hb results in
      decreased haemoglobin-oxygen (Hb-O2) affinity, improved tumour oxygenation, and
      enhanced radiation-induced cell killing in several experimental tumour systems.
      In the present work, ex vivo clonogenic survival analyses are applied in two
      murine tumour systems to characterize the relationship between the magnitude of
      decrease in Hb-O2 affinity and radiosensitization, the influence of inspired pO2
      upon this effect, and the efficacy of combining RSR13 and radiation during a
      course of repeated radiation exposures. For FSaII tumours in C3H mice breathing
      air, 100 mg kg(-1) RSR13 administered intraperitoneally produced an enhancement
      ratio (ER) of 1.3, but there was marked desensitization at a RSR13 dose of 300 mg
      kg(-1) (ER 0.6). The most likely reason for the increased radioresistance was
      insufficient oxygen loading of Hb in the pulmonary circulation due to reduced
      haemoglobin-oxygen affinity because carbogen breathing combined with 300 mg kg(
      1) RSR13 reversed the effect and produced an ER of 1.8. In SCCVII tumours in C3H
      mice irradiated with eight fractions of 2.5 Gy over 4 days, the surviving
      fraction was reduced to 58-67% of control values when RSR13 was combined with
      radiation on days 1 and 2, days 3 and 4, or days 1-4. These results confirm that
      combining RSR13 and irradiation within a fractionated course of clinically
      relevant low-dose exposures provides significant radiosensitization. Additional
      preclinical experimentation is needed to define better the optimum dose
      scheduling conditions for clinical applications.

PMID- 10070875
TI  - High efficiency of benzoporphyrin derivative in the photodynamic therapy of
      pigmented malignant melanoma.
AB  - Benzoporphyrin derivative monoacid ring A (verteporfin, BPD-MA) when
      intravenously injected (5.5 micromol kg(-1)) to C57/BL6 mice bearing a
      subcutaneously transplanted B1 melanoma gave a maximal accumulation in the tumour
      within 1-3 h with recoveries of 1.84-1.96 micromol kg(-1). Irradiation of BPD-MA
      loaded melanoma with 690-nm light from a dye laser at 3 h and 9 h post injection
      induced tumour necrosis and delay of tumour growth of 28 and 14 days
      respectively. The response of the tumour to BPD-MA photosensitization was
      enhanced by pretreatment with 1064-nm light from a pulse-operated Nd:YAG laser,
      which caused a selective breakdown of melanosomes.

PMID- 10070876
TI  - Timing of illumination is essential for effective and safe photodynamic therapy:
      a study in the normal rat oesophagus.
AB  - 5-Aminolaevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)-mediated
      photodynamic therapy (PDT) is an experimental treatment modality for
      (pre)malignant oesophageal lesions. This study aimed to optimize the time of
      illumination after ALA administration. Six groups of eight rats received 200 mg
      kg(-1) ALA orally, eight rats served as controls. Illumination was performed at
      1, 2, 3, 4, 6 or 12 h after ALA administration with a 1-cm cylindrical diffuser
      placed in a balloon catheter (laser parameters: 633 nm, 25 J radiant energy,
      power output 100 mW). During illumination, fluorescence measurements and light
      dosimetry were performed. Animals were sacrificed at 48 h (n = 4) or 28 days (n =
      4) after PDT. At day 28, an oesophagogram was performed. Largest PpIX
      fluorescence was found at 3 h after ALA administration. In vivo fluence rate was
      three times higher than the calculated incident fluence rate. At 48 h after PDT,
      major epithelial damage was found in all animals illuminated at 2 h, whereas less
      epithelial damage was found at 3-6 h and none at 1 and 12 h. In animals
      illuminated at 4, 6 and 12 h, but not at 2 h, oesophagograms showed severe
      dilatations and histology showed loss of Schwann cells. These results demonstrate
      that the choice of time interval between ALA administration and illumination is
      critical for achieving epithelial damage without oesophageal functional
      impairment. A short interval of 2-3 h seems to be most appropriate.

PMID- 10070877
TI  - Induction of MDR1 gene expression by anthracycline analogues in a human drug
      resistant leukaemia cell line.
AB  - The effects of 4-demethoxydaunorubicin (idarubicin, IDA) and MX2, a new
      morpholino-anthracycline, on up-regulation of the MDR1 gene in the low-level
      multidrug resistant (MDR) cell line CEM/A7R were compared at similar
      concentrations (IC10, IC50 and IC90) over a short time exposure (4 and 24 h). The
      chemosensitivity of each drug was determined by a 3-day cell growth inhibition
      assay. Compared with epirubicin (EPI), IDA and MX2 were 17- and eightfold more
      effective in the CEM/A7R line respectively. No cross-resistance to 5-FU was seen
      in the CEM/A7R line. Verapamil (5 microM) and PSC 833 (1 microM), which
      dramatically reversed resistance to EPI in the CEM/A7R line, had no sensitizing
      effect on the resistance of this line to MX2, but slightly decreased resistance
      to IDA. The sensitivity to 5-FU was unchanged by these modulators. The induction
      of MDR1 mRNA expression by IDA, MX2 and 5-FU was analysed by Northern blotting
      and semiquantitatively assessed by scanning Northern blots on a phosphorimager.
      The relative level of MDR1 expression was expressed as a ratio of MDR1 mRNA to
      the internal RNA control glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IDA,
      MX2 and 5-FU differentially up-regulated MDR1 mRNA in the CEM/A7R line in a dose
      dependent manner. Both IDA and MX2 induced MDR1 expression within 4 h. 5-FU up
      regulated MDR1 expression only when drug exposure was prolonged to 24 h. Based on
      MRK 16 binding, flow cytometric analysis of P-glycoprotein (Pgp) expression
      paralleled the increase in MDR1 mRNA levels. For the three anthracyclines, the
      increase in MDR1 expression was stable in cells grown in the absence of drug for
      more than 3 weeks after drug treatment. The induction of MDR1 expression by 5-FU
      was transient, associated with a rapid decrease in the increased Pgp levels which
      returned to baseline 72 h after the removal of 5-FU. This study demonstrates that
      MDR1 expression can be induced by analogues of anthracyclines not pumped by Pgp,
      and that this induction appears to be stable despite a 3-week drug-free period.

PMID- 10070878
TI  - The pH partition theory predicts the accumulation and toxicity of doxorubicin in
      normal and low-pH-adapted cells.
AB  - The accumulation and toxicity of the weak base doxorubicin has been investigated
      as a function of extracellular pH, intracellular pH and the cellular pH gradient
      in cells previously cultured under normal (pH 7.4) and low-pH (6.8) conditions.
      Low-pH-adapted cells exhibit transmembrane pH gradients which substantially
      differ from normal cells at the same extracellular pH. No relationship was
      obtained between intracellular pH and the uptake or toxicity of doxorubicin in
      the two cell types. In contrast, doxorubicin accumulation and toxicity increased
      with increasing extracellular pH in both normal and low-pH-adapted cells.
      However, at the same extracellular pH, drug cytotoxicity was more pronounced in
      normal than in low-pH-adapted cells. The difference in doxorubicin accumulation
      and cytotoxicity at the same extracellular pH was found to be dependent on the
      difference in the transmembrane pH gradient of the two cell types. As the
      cellular pH gradient differs between tumour and normal tissue, this observation
      suggests a basis for enhancing cellular drug uptake in either tissue type.

PMID- 10070879
TI  - Modification of non-conservative double-strand break (DSB) rejoining activity
      after the induction of cisplatin resistance in human tumour cells.
AB  - The induction of collateral radioresistance after the development of cisplatin
      resistance is a well-documented phenomenon; however, the exact processes that are
      responsible for the cisplatin-induced radioresistance remain to be elucidated.
      There was no obvious difference in the level of radiation-induced DNA double
      strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic
      subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and
      radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However,
      there was a significantly (P < 0.01) lower level of DSB misrejoining activity
      within nuclear protein extracts derived from the cisplatin- and radiation
      sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from
      their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts.
      All of the DSB misrejoining events involved deletions of between 134 and 444 bp
      that arose through illegitimate recombination at short repetitive sequences, such
      as those that arise through non-homologous repair (NHR). These data further
      support the notion that the radiosensitivity of DSB repair proficient human
      tumour cell lines may be partly determined by the predisposition of these cell
      lines to activate non-conservative DSB rejoining pathways. Furthermore, our data
      suggest that the induction of acquired cisplatin resistance is associated with a
      two- to threefold decrease in the activity of a non-conservative DSB rejoining
      mechanism that appears to be a manifestation of NHR.

PMID- 10070880
TI  - Analysis of the interaction of monoclonal antibodies with surface IgM on
      neoplastic B-cells.
AB  - In vitro studies identified three Burkitts lymphoma cell lines, Ramos, MUTU-I and
      Daudi, that were growth inhibited by anti-IgM antibody. However, only Ramos and
      MUTU-I were sensitive to monoclonal antibodies (mAb) recognizing the Fc region of
      surface IgM (anti-Fc mu). Experiments using anti-Fc mu mAb (single or non
      crossblocking pairs), polyclonal anti-mu Ab, and hyper-crosslinking with a
      secondary layer of Ab, showed that growth inhibition of B-cell lines was highly
      dependent on the extent of IgM crosslinking. This was confirmed by using Fab',
      F(ab')2 and F(ab')3 derivatives from anti-Fc mu mAb, where increasing valency
      caused corresponding increases in growth arrest and apoptosis, presumably as a
      result of more efficient BCR-crosslinking on the cell surface. The ability of a
      single mAb to induce growth arrest was highly dependent on epitope specificity,
      with mAb specific for the Fc region (C mu2-C mu4 domains) being much more
      effective than those recognizing the Fab region (anti-L chain, anti-Id and anti
      Fd mu, or C mu1). Only when hyper-crosslinked with polyclonal anti-mouse IgG did
      the latter result in appreciable growth inhibition. Binding studies showed that
      these differences in function were not related to differences in the affinity,
      but probably related to intrinsic crosslinking capacity of mAb.

PMID- 10070881
TI  - The influence on survival of delay in the presentation and treatment of
      symptomatic breast cancer.
AB  - The aim of this study was to examine the possible influence on survival of delays
      prior to presentation and/or treatment among women with breast cancer. Duration
      of symptoms prior to hospital referral was recorded for 2964 women who presented
      with any stage of breast cancer to Guy's Hospital between 1975 and 1990. Median
      follow-up is 12.5 years. The impact of delay (defined as having symptoms for 12
      or more weeks) on survival was measured from the date of diagnosis and from the
      date when the patient first noticed symptoms to control for lead-time bias.
      Thirty-two per cent (942/2964) of patients had symptoms for 12 or more weeks
      before their first hospital visit and 32% (302/942) of patients with delays of 12
      or more weeks had locally advanced or metastatic disease, compared with only 10%
      (210/2022) of those with delays of less than 12 weeks (P < 0.0001). Survival
      measured both from the date of diagnosis (P < 0.001) and from the onset of the
      patient's symptoms (P = 0.003) was worse among women with longer delays. Ten
      years after the onset of symptoms, survival was 52% for women with delays less
      than 12 weeks and 47% for those with longer delays. At 20 years the survival
      rates were 34% and 24% respectively. Furthermore, patients with delays of 12-26
      weeks had significantly worse survival rates than those with delays of less than
      12 weeks. Multivariate analyses indicated that the adverse impact of delay in
      presentation on survival was attributable to an association between longer delays
      and more advanced stage. However, within individual stages, longer delay had no
      adverse impact on survival. Analyses based on 'total delay (i.e. the interval
      between a patient first noticing symptoms and starting treatment) yielded very
      similar results in terms of survival to those based on delay to first hospital
      visit (delay in presentation).

PMID- 10070882
TI  - The role of genetic factors in predisposition to squamous cell cancer of the head
      and neck.

PMID- 10070883
TI  - The impact of genetic counselling on risk perception and mental health in women
      with a family history of breast cancer.
AB  - The present study investigated: (1) perception of genetic risk and, (2) the
      psychological effects of genetic counselling in women with a family history of
      breast cancer. Using a prospective design, with assessment pre- and post-genetic
      counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders
      at four South London genetic clinics were assessed. Participants included 282
      women with a family history of breast cancer. Outcome was measured in terms of
      mental health, cancer-specific distress and risk perception. High levels of
      cancer-specific distress were found pre-genetic counselling, with 28% of
      participants reporting that they worried about breast cancer 'frequently or
      constantly' and 18% that worry about breast cancer was 'a severe or definite
      problem'. Following genetic counselling, levels of cancer-specific distress were
      unchanged. General mental health remained unchanged over time (33% psychiatric
      cases detected pre-genetic counselling, 27% at 12 months after genetic
      counselling). Prior to their genetics consultation, participants showed poor
      knowledge of their lifetime risk of breast cancer since there was no association
      between their perceived lifetime risk (when they were asked to express this as a
      1 in x odds ratio) and their actual risk, when the latter was calculated by the
      geneticist at the clinic using the CASH model. In contrast, women were more
      accurate about their risk of breast cancer pre-genetic counselling when this was
      assessed in broad categorical terms (i.e. very much lower/very much higher than
      the average woman) with a significant association between this rating and the
      subsequently calculated CASH risk figure (P = 0.001). Genetic counselling
      produced a modest shift in the accuracy of perceived lifetime risk, expressed as
      an odds ratio, which was maintained at 12 months' follow-up. A significant
      minority failed to benefit from genetic counselling; 77 women continued to over
      estimate their risk and maintain high levels of cancer-related worry. Most clinic
      attenders were inaccurate in their estimates of the population risk of breast
      cancer with only 24% able to give the correct figure prior to genetic counselling
      and 36% over-estimating this risk. There was some improvement following genetic
      counselling with 62% able to give the correct figure, but this information was
      poorly retained and this figure had dropped to 34% by the 1-year follow-up. The
      study showed that women attending for genetic counselling are worried about
      breast cancer, with 34% indicating that they had initiated the referral to the
      genetic clinic themselves. This anxiety is not alleviated by genetic counselling,
      although women reported that it was less of a problem at follow-up. Women who
      continue to over-estimate their risk and worry about breast cancer are likely to
      go on seeking unnecessary screening if they are not reassured.

PMID- 10070884
TI  - Phase II study of gemcitabine and vindesine in patients with previously untreated
      non-resectable non-small-cell lung cancer.
AB  - Because both vindesine and gemcitabine are active drugs in advanced non-small
      cell lung cancer (NSCLC), with different modes of action and only partly
      overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m(-2)
      was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m(-2) was
      administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with
      nonresectable NSCLC were included. The median age of patients was 56 years; 57%
      were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large
      cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance
      status 1. The majority (55%) had stage IV disease, while 40% had stage III B and
      5% stage III A disease. WHO grade 3-4 leucopenia occurred in five patients (12%)
      and 9% had grade 4 neutropenia. Thrombocytopenia grade 3-4 was observed in six
      patients (15%). There were no septic death or bleeding episodes. One patient had
      a transient WHO grade 4 increase in bilirubin, and four patients had a decrease
      in glomerular filtration rate below the normal limit; one of these patients
      developed a non-reversible renal insufficiency. Ten patients (24%) complained of
      dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There
      were one complete and seven partial responses among 40 assessable patients (20%,
      95% confidence limits 9-36%). Median response duration was 31 weeks (range 11-83
      weeks) and median survival time 31 weeks (range 2-171 weeks). The current
      combination of gemcitabine and vindesine does not appear to be promising for
      further examination because of the toxicity and somewhat disappointing activity.

PMID- 10070885
TI  - Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor
      fostriecin.
AB  - We conducted a phase I and pharmacokinetic study of the topoisomerase II
      catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60
      min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1)
      to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with
      high performance liquid chromatography with UV-detection. Plasma collected during
      drug administration was tested in vitro for growth inhibition of a teniposide
      resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities
      were elevated liver transaminases (maximum common toxicity criteria (CTC) grade
      4) and serum creatinine (maximum CTC grade 2). These showed only a limited
      increase with increasing doses, often recovered during drug administration and
      were fully reversible. Duration of elevated alanine-amino transferase (ALT) was
      dose-limiting in one patient at 20 mg m(-2). Other frequent toxicities were grade
      1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was
      0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% CI, 0.41-2.61 h). A
      metabolite, most probably dephosphorylated fostriecin, was detected in plasma and
      urine. No tumour responses were observed, but the plasma concentrations reached
      in the patients were insufficient to induce significant growth inhibition in
      vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply
      was stopped at the 20 mg m(-2) dose level. However, further escalation seems
      possible and is warranted to achieve potentially effective drug levels.
      Fostriecin has a short plasma half-life and longer duration of infusion should be
      considered.

PMID- 10070886
TI  - Expression of prostate-specific antigen (PSA) correlates with poor response to
      tamoxifen therapy in recurrent breast cancer.
AB  - Prostate-specific antigen (PSA) is a serine protease which may play a role in a
      variety of cancer types, including breast cancer. In the present study, we
      evaluated whether the level of PSA in breast tumour cytosol could be associated
      with prognosis in primary breast cancer, or with response to tamoxifen therapy in
      recurrent disease. PSA levels were determined by enzyme-linked immunosorbent
      assay (ELISA) in breast tumour cytosols, and were correlated with prognosis in
      1516 patients with primary breast cancer and with response to first-line
      tamoxifen therapy in 434 patients with recurrent disease. Relating the levels of
      PSA with classical prognostic factors, low levels were more often found in larger
      tumours, tumours of older and post-menopausal patients, and in steroid hormone
      receptor-negative tumours. There was no significant association between the
      levels of PSA with grade of differentiation or the number of involved lymph
      nodes. In patients with primary breast cancer, PSA was not significantly related
      to the rate of relapse, and a positive association of PSA with an improved
      survival could be attributed to its relationship to age. In patients with
      recurrent breast cancer, a high level of PSA was significantly related to a poor
      response to tamoxifen therapy, and a short progression-free and overall survival
      after start of treatment for recurrent disease. In Cox multivariate analyses for
      response to therapy and for (progression-free) survival, corrected for
      age/menopausal status, disease-free interval, site of relapse and steroid hormone
      receptor status, PSA was an independent variable of poor prognosis. It is
      concluded that the level of PSA in cytosols of primary breast tumours might be a
      marker to select breast cancer patients who may benefit from systemic tamoxifen
      therapy.

PMID- 10070887
TI  - p21(WAF1/CIP1) expression in stage I cutaneous malignant melanoma: its
      relationship with p53, cell proliferation and survival.
AB  - The expression of p21, p53 and proliferating cell nuclear antigen (PCNA) was
      analysed by immunohistochemistry in a consecutive series of 369 clinical stage I
      cutaneous malignant melanoma patients. Correlation of the detected expression
      levels with each other, with clinicopathological data and with melanoma survival
      were statistically evaluated. p21 expression was significantly associated with
      p53 and PCNA expression levels. In addition, high levels of p53 and PCNA were
      significantly interrelated. Tumour thickness, recurrent disease, high TNM
      category and older (> or = 55 years) age at diagnosis were inversely associated
      with p21 expression. Gender, bleeding, tumour thickness, Clark's level of
      invasion, TNM category and p53 index were all important predictors of both
      recurrence-free and overall survival of melanoma. In Cox's multivariate analysis
      including 164 patients with a complete set of data, only high tumour thickness
      and bleeding predicted poor recurrence-free survival (P = 0.0042 and 0.0087
      respectively) or overall survival (P = 0.0147 and 0.0033 respectively). Even
      though elevated p21 expression may be associated with more favourable prognosis
      in clinical stage I cutaneous melanoma, our results suggest that cell cycle
      regulatory effects of p21 can be overcome by some other and stronger, partly yet
      unknown, mechanisms.

PMID- 10070888
TI  - Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor
      prognosis in a subset of colorectal cancers.
AB  - Adjuvant therapies are increasingly used in colorectal cancers for the prevention
      of recurrence. These therapies have side-effects and should, thus, be used only
      if really beneficial. However, the development of recurrence cannot be predicted
      reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus
      based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in
      the long arm of chromosome 18 is suggested to be related to poor survival and
      possibly to the development of metastases. We studied the value of LOH at 18q21
      as a marker of colorectal cancer prognosis, association with clinicopathological
      variables, tumour recurrence and survival of the patients. Of the 255 patients
      studied, 195 were informative as regards LOH status when analysed in primary
      colorectal cancer specimens using the polymerase chain reaction (PCR) and
      fragment analysis. LOH at 18q21 was significantly associated with the development
      of recurrence (P = 0.01) and indicated poor survival in patients of Dukes'
      classes B and C, in which most recurrences (82%) occurred. An increased rate of
      tumour recurrence is the reason for poor survival among patients with LOH at
      18q21 in primary cancer. These patients are a possible target group for
      recurrence-preventing adjuvant therapies.

PMID- 10070889
TI  - Time at surgery during menstrual cycle and menopause affects pS2 but not
      cathepsin D levels in breast cancer.
AB  - Many studies have addressed the clinical value of pS2 as a marker of hormone
      responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast
      cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer
      cell lines, we studied the influence of the menstrual cycle phase and menopausal
      status at the time of surgery on the levels of these proteins in breast cancer. A
      population of 1750 patients with breast cancer, including 339 women in menstrual
      cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay.
      Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH) levels at the day of surgery were used to define the
      hormonal phase in premenopausal women. There was a trend towards a higher mean
      pS2 level in the follicular phase compared with the luteal phase (17 ng mg(-1)
      and 11 ng mg(-1) respectively, P = 0.09). Mean pS2 was lower in menopausal
      patients than in women with cycle (8 ng mg(-1) and 14 ng mg(-1) respectively, P =
      0.0001). No differences in mean Cath D level were observed between the different
      phases of the menstrual cycle, or between pre- and post-menopausal women. In the
      overall population, pS2 was slightly positively associated with E2 and Pg levels
      and negatively associated with FSH and LH, probably reflecting the link between
      pS2 and menopausal status. In premenopausal women, no association was found
      between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath
      D level and circulating hormone levels in the overall population. However, in the
      subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly
      associated with both pS2 and Cath D, consistent with oestrogen induction of these
      proteins in ER+ breast cancer cell lines. There are changes in pS2 level in
      breast cancer throughout the menstrual cycle and menopause. This suggests that
      the choice of the pS2 cut-off level should take the hormonal status at the time
      of surgery into account. In contrast, the level of Cath D is unrelated to the
      menstrual cycle and menopausal status.

PMID- 10070890
TI  - A phase I study of the lipophilic thymidylate synthase inhibitor Thymitaq
      (nolatrexed dihydrochloride) given by 10-day oral administration.
AB  - 2-Amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride
      (nolatrexed dihydrochloride, Thymitaq, AG337), a specific inhibitor of
      thymidylate synthase, was developed using protein structure-based drug design.
      Intravenously administered nolatrexed is active clinically. As oral
      bioavailability is high (70-100%), nolatrexed was administered orally, 6 hourly
      for 10 days, at 3-week intervals, and dose escalated from 80 to 572 mg m(-2) day(
      1) in 23 patients. Common toxicity criteria (CTC) grade 3 toxicities included
      nausea, vomiting, stomatitis and liver function test (LFT) abnormalities.
      Thrombocytopenia (grade 1 or 2) occurred at doses > or = 318 mg m(-2) day(-1) and
      neutropenia (grade 2) at 429 and 572 mg m(-2) day(-1). An erythematous
      maculopapular rash occurred at dosages > or = 318 mg m(-2) day(-1) (7 out of 19
      patients). LFT abnormalities occurred in two out of six patients (grade 3 or 4
      bilirubin and grade 3 alanine transaminase) at 572 mg m(-2) day(-1). Nolatrexed
      plasma concentrations 1 h after dosing were 6-16 microg ml(-1), and trough 3-8
      microg ml(-1), at 572 mg m(-2) day(-1). Inhibition of thymidylate synthase was
      demonstrated by elevation of plasma deoxyuridine. Six-hourly oral nolatrexed for
      10 days was associated with antiproliferative effects, but nausea and vomiting
      was dose limiting at 572 mg m(-2) day(-1). Nine patients were treated at 429 mg
      m(-2) day(-1); three out of nine experienced grade 3 nausea, but 17 out of 22
      treatment courses were completed (with the co-administration of prophylactic
      antiemetics) and this dose level could be considered for phase II testing.

PMID- 10070891
TI  - p53 mutations in human cutaneous melanoma correlate with sun exposure but are not
      always involved in melanomagenesis.
AB  - In melanoma, the relationship between sun exposure and the origin of mutations in
      either the N-ras oncogene or the p53 tumour-suppressor gene is not as clear as in
      other types of skin cancer. We have previously shown that mutations in the N-ras
      gene occur more frequently in melanomas originating from sun-exposed body sites,
      indicating that these mutations are UV induced. To investigate whether sun
      exposure also affects p53 in melanoma, we analysed 81 melanoma specimens for
      mutations in the p53 gene. The mutation frequency is higher than thus far
      reported: 17 specimens (21%) harbour one or more p53 mutations. Strikingly, 17
      out of 22 mutations in p53 are of the C:G to TA or CC:GG to TT:AA transitional
      type, strongly suggesting an aetiology involving UV exposure. Interestingly, the
      p53 mutation frequency in metastases was much lower than in primary tumours. In
      the case of metastases, a role for sun exposure was indicated by the finding that
      the mutations are present exclusively in skin metastases and not in internal
      metastases. Together with a relatively frequent occurrence of silent third-base
      pair mutations in primary melanomas, this indicates that the p53 mutations, at
      least in these tumours, have not contributed to melanomagenesis and may have
      originated after establishment of the primary tumour.

PMID- 10070892
TI  - Serum antibodies against p53 in relation to cancer risk and prognosis in breast
      cancer: a population-based epidemiological study.
AB  - To perform an epidemiological evaluation of the predictive value of p53
      autoantibodies in breast cancer, we measured antibodies against p53 in serum
      samples from 165 breast cancer patients in comparison with serum samples from 330
      healthy controls, selected from the same population as the cases and matched for
      age, sex and specimen storage time. Median age of patients was 51 years (range 25
      64 years). Presence of serum p53 autoantibodies was analysed by enzyme-linked
      immunosorbent assay (ELISA) and confirmed by Western blotting. The lower ELISA
      reactivities were similar for cases and controls, but presence of high-level
      reactivity was more common among cases than among controls [odds ratio (OR) 9.03,
      95% confidence interval (CI) 2.40-50.43]. Presence of Western blot-detected p53
      autoantibodies had a very similar association (OR 10.8, CI 3.0-59.4). Among the
      cases, we also studied whether there was any correlation between level of anti
      p53 antibodies and stage of the disease or survival. There was no significant
      correlation between presence of antibodies and stage of the disease. There was a
      significant negative correlation between presence of p53 antibodies and survival
      (P = 0.003). A stepwise multivariate Cox regression analysis showed that T-stage,
      age and presence of anti-p53 antibodies were significant independent prognostic
      variables, with a dose-dependent negative effect on survival for all three
      variables. We conclude that presence of anti-p53 antibodies are of significance
      both for the risk of having breast cancer and the risk of dying from breast
      cancer.

PMID- 10070893
TI  - Increased expression of the RIalpha subunit of the cAMP-dependent protein kinase
      A is associated with advanced stage ovarian cancer.
AB  - The primary element in the cAMP signal transduction pathway is the cAMP-dependent
      protein kinase (PKA). Expression of the RIalpha subunit of type I PKA is elevated
      in a variety of human tumours and cancer cell lines. The purpose of this study
      was to assess the prognostic importance of RIalpha expression in patients with
      ovarian cancer. We have evaluated the expression of RIalpha in a panel of human
      ovarian tumours (n = 40) and five human ovarian cancer cell lines using
      quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western
      blot analysis. The human ovarian cell lines OAW42 and OTN14 express high
      endogenous levels of RIalpha mRNA and protein (at significantly higher mRNA
      levels than high tissue expressors, P < 0.05). The ovarian cell line A2780
      expresses low endogenous levels of RIalpha mRNA and protein (also at higher mRNA
      levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no
      significant difference in RIalpha mRNA expression between different ovarian
      histological subtypes in this study. No associations were found between RIalpha
      mRNA expression and differentiation state. RIalpha mRNA expression was
      significantly associated with tumour stage (P = 0.0036), and this remained
      significant in univariate analysis (P = 0.0002). A trend emerged between RIalpha
      mRNA expression levels and overall survival in univariate analysis (P = 0.051),
      however, by multivariate analysis, stage remained the major determinant of
      overall survival (P = 0.0001). This study indicates that in ovarian epithelial
      tumours high RIalpha mRNA expression is associated with advanced stage disease.
      RIalpha expression may be of predictive value in ovarian cancer and may be
      associated with dysfunctional signalling pathways in this cancer type.

PMID- 10070894
TI  - Immunohistochemical localization of CD1a-positive putative dendritic cells in
      human breast tumours.
AB  - The presence of a high number of infiltrating CD1a+ cells in malignant neoplasms
      has been reported to be associated with an improved prognosis, reduced tumour
      recurrence and fewer metastases. This study identified a population of CD1a+
      cells within the lymphoid cell infiltrate in human ductal breast carcinoma (n =
      52), which was significantly different from normal breast tissue, in which only
      two out of nine cases expressed CD1a+ cells (P = 0.0192). In the majority of
      cases, the infiltrate was low compared with the number of macrophages and T cells
      present (results not shown). There was no correlation between the number of CD1a+
      cells and tumour grade, with all tumour grades expressing similar numbers of
      infiltrating CD1a+ cells. There was clear evidence, however, that the CD1a+ cells
      were closely associated with tumour cells. It is likely that CD1a+ cells have a
      role in antigen capture and presentation in human tumours, and this study
      documents the density of CD1a+ cells in a large sample of all histological grades
      of human breast carcinomas.

PMID- 10070895
TI  - Comparison of the Ki-67 score and S-phase fraction as prognostic variables in
      soft-tissue sarcoma.
AB  - Immunohistochemically determined Ki-67 scores and flow cytometrically determined
      S-phase fractions were successfully evaluated from the primary tumours of 123
      patients with soft-tissue sarcoma. All patients had either limb or superficial
      trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and
      grade. Ki-67 did not correlate with the size of the primary tumour. When analysed
      as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free
      survival and disease-specific overall survival (P = 0.003 and 0.04 respectively)
      than was the S-phase fraction (P = 0.06 and 0.07 respectively). We tested the
      relevance of different cut-point values by dividing the whole material into two
      parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%,
      etc.). We counted the relative risk and confidence interval at all these cut-off
      points. Ki-67 had good prognostic discriminating power irrespective of the cut
      point value, but S-phase fraction lost its prognostic power at higher cut-point
      values. In conclusion, we found that Ki-67 is a useful prognostic tool in the
      treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S
      phase fraction can be used at lower cut-point values.

PMID- 10070896
TI  - Expression of apoptosis regulatory proteins of the Bcl-2 family and p53 in
      primary resected non-small-cell lung cancer.
AB  - Proteins of the Bcl-2 family as well as p53 are important regulators of
      apoptosis. Alterations in the expression of these proteins can contribute to the
      formation of cancer, as well as influence tumour response to chemo- and
      radiotherapy. We used antibodies specific for the human Bcl-2, Mcl-1, Bax, Bak
      and p53 proteins to examine the expression of these apoptosis-regulating genes in
      49 archival specimens of patients with radically resected non-small-cell lung
      cancer (NSCLC). Tumour cells containing immunostaining for the antiapoptotic
      proteins Bcl-2 and Mcl-1 were present in 31% and 58% of the cases evaluated,
      respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak
      was found in 47% and 58% of the samples. p53 immunopositivity was detected in 61%
      of the samples. The expression of Bcl-2 and p53 and the expression of Mcl-1 and
      Bax showed a positive association (P = 0.02 and P = 0.06 respectively), whereas
      the expression of Bax was inversely related to p53 (P = 0.008). The expression of
      Bcl-2 had a negative influence on relapse-free survival in this population of
      primary resected NSCLC patients (P = 0.02). The expression of p53 and Bcl-2 was
      significantly associated with metastasis-free survival (P < 0.01). Only patients
      with p53-positive tumours developed metastases during the follow-up period. Our
      results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl
      1, Bax and Bak in NSCLC. It can be expected that Bcl-2 family members have no
      straightforward impact on clinical outcome in this disease because their
      interactions in the regulation of apoptosis are complex.

PMID- 10070897
TI  - Androgen receptor expression in male breast carcinoma: lack of
      clinicopathological association.
AB  - Androgen receptor (AR) expression was retrospectively analysed in 47 primary male
      breast carcinomas (MBCs) using a monoclonal antibody on formalin-fixed, paraffin
      embedded tissues. AR immunopositivity was detected in 16 out of 47 (34%) cases.
      No association was found with patient age, tumour stage, progesterone receptor
      (PGR) or p53 protein expression. Well-differentiated MBCs tended to be AR
      positive more often than poorly differentiated ones (P = 0.08). A negative
      association was found between ARs and cell proliferative activity: MIB-1 scores
      were higher (25.4%) in AR-negative than in AR-positive cases (21.11%; P = 0.04).
      A strong positive association (P = 0.0001) was found between ARs and oestrogen
      receptors (ERs). In univariate analysis, ARs (as well as ERs and PGRs) were not
      correlated with overall survival; tumour histological grade (P = 0.02), size (P =
      0.01), p53 expression (P = 0.0008) and MIB-1 scores (P = 0.0003) had strong
      prognostic value. In multivariate survival analysis, only p53 expression (P =
      0.002) and histological grade (P = 0.02) retained independent prognostic
      significance. In conclusion, the lack of association between AR and most
      clinicopathological features and survival, together with the absence of
      prognostic value for ER/PGR status, suggest that MBCs are biologically different
      from female breast carcinomas and make it questionable to use antihormonal
      therapy for patients with MBC.

PMID- 10070898
TI  - Angiogenesis extent and macrophage density increase simultaneously with
      pathological progression in B-cell non-Hodgkin's lymphomas.
AB  - Node biopsies of 30 benign lymphadenopathies and 71 B-cell non-Hodgkin's
      lymphomas (B-NHLs) were investigated for microvessel and macrophage counts using
      immunohistochemistry and morphometric analysis. Both counts were significantly
      higher in B-NHL. Moreover, when these were grouped into low-grade and high-grade
      lymphomas, according to the Kiel classification and Working Formulation (WF),
      statistically significant higher counts were found in the high-grade tumours.
      Immunohistochemistry and electron microscopy revealed a close spatial association
      between microvessels and macrophages. Overall, the results suggest that, in
      analogy to what has already been shown in solid tumours, angiogenesis occurring
      in B-NHLs increases with tumour progression, and that macrophages promote the
      induction of angiogenesis via the release of their angiogenic factors.

PMID- 10070899
TI  - Improved methods using the reverse transcriptase polymerase chain reaction to
      detect tumour cells.
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR) is increasingly used to
      detect small numbers of circulating tumour cells, though the clinical benefit
      remains controversial. The largest single contributing factor to the controversy
      of its value is the different approaches to sample processing. The aim of this
      study was to compare the sensitivity and reproducibility of RT-PCR for the
      detection of tumour cells after four commonly used different methods of sample
      processing. Using RT-PCR, one tumour cell spiked in 2 ml of whole blood was
      detected after analysis of separated mononuclear cell RNA, whole blood total or
      poly-A+ RNA. No false positives were identified with any method. However, the
      reproducibility of tumour cell detection was reduced after isolation of the
      mononuclear cell fraction. Only analysis of poly-A+ RNA had a sensitivity of 100%
      in all the cell spiking experiments. In patient blood samples, analysis of poly
      A+ RNA increased the number of blood samples positive for tyrosine hydroxylase
      (TH) mRNA compared with those positive after analysis of total RNA. This may
      reflect high levels of cDNA reducing the efficiency of the PCR. Isolation of poly
      A+ RNA increases the sensitivity and reproducibility of tumour cell detection in
      peripheral blood.

PMID- 10070900
TI  - Oestrogen receptor-alpha variant mRNA expression in primary human breast tumours
      and matched lymph node metastases.
AB  - We have shown previously that the relative expression of a truncated oestrogen
      receptor-alpha variant mRNA (ER clone 4) is significantly increased in axillary
      node-positive primary breast tumours compared with node-negative tumours. In this
      study, we have examined the relative expression of clone 4-truncated, exon 5
      deleted and exon 7-deleted oestrogen receptor-alpha variant mRNAs in 15 primary
      breast tumour samples and in synchronous axillary lymph node metastases. Overall,
      there were no significant differences between the primary tumours and the matched
      metastases in the relative expression of these three specific variant mRNAs.
      Furthermore, the pattern of all deleted oestrogen receptor-alpha variant mRNAs
      appeared conserved between any primary and its matched secondary tumour.

PMID- 10070901
TI  - Fractionated administration of irinotecan and cisplatin for treatment of lung
      cancer: a phase I study.
AB  - A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been
      reported to be active for lung cancer. In the previous trial, however, diarrhoea
      and leucopenia became the major obstacle for sufficient dose escalation of CPT-11
      to improve the treatment outcome. We conducted a phase I study to investigate
      whether the fractionated administration of CDDP and CPT-11 at escalated dose was
      feasible and could improve the treatment outcome. Twenty-four previously
      untreated patients with unresectable non-small-cell lung cancer (NSCLC) or
      extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and
      CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP
      was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration.
      The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an
      increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as
      60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological
      toxicities developed in six patients out of 11 patients evaluated. Diarrhoea
      became a dose-limiting toxicity. The objective response rates were 76% for NSCLC
      and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study
      will be 50 mg m(-2) and 60 mg m(-2) respectively.

PMID- 10070902
TI  - Necrosis correlates with high vascular density and focal macrophage infiltration
      in invasive carcinoma of the breast.
AB  - Necrosis is a common feature of invasive carcinoma of the breast and is caused by
      chronic ischaemia leading to infarction. Although necrosis was previously assumed
      to be due to a generally poor blood supply in the tumour, in this study we show
      that it is present in tumours with focal areas of high vascular density situated
      away from the actual sites of necrosis. This may account, in part, for the
      previous observation that necrosis is linked to poor prognosis in this disease.
      Highly angiogenic tumours often display blood vessel shunting from one tumour
      area to another, which further exacerbates ischaemia and the formation of tumour
      necrosis. We have recently demonstrated that high focal microphage infiltration
      into breast tumours is significantly associated with increased tumour
      angiogenesis and poor prognosis and that the macrophages accumulate in poorly
      vascularized, hypoxic areas within breast tumours. In order to investigate the
      interactions of macrophages with chronic ischaemia (as reflected by the presence
      of necrosis) and angiogenesis in breast tumours, we quantified the levels of
      these three biological parameters in a series of 109 consecutive invasive breast
      carcinomas. We found that the degree of tumour necrosis was correlated with both
      microphage infiltration (Mann-Whitney U, P-value = 0.0009; chi-square, P-value =
      0.01) and angiogenesis (Mann-Whitney U P-value = 0.0008, chi square P-value =
      0.03). It was also observed that necrosis was a feature of tumours possessing an
      aggressive phenotype, i.e. high tumour grade (chi-square, P-value < 0.001),
      larger size (Mann-Whitney U, P-value = 0.003) and low oestrogen receptor status
      (Mann-Whitney U, P-value = 0.008; chi-square, P-value < 0.008). We suggest,
      therefore, that aggressive tumours rapidly outgrow their vascular supply in
      certain areas, leading to areas of prolonged hypoxia within the tumour and,
      subsequently, to necrosis. This, in turn, may attract macrophages into the
      tumour, which then contribute to the angiogenic process, giving rise to an
      association between high levels of angiogenesis and extensive necrosis.

PMID- 10070903
TI  - Apoptotic activity is increased in parallel with the metaplasia-dysplasia
      carcinoma sequence of the bronchial epithelium.
AB  - A high level of apoptotic activity and an independence of apoptosis from the
      expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma.
      We examined 44 samples of normal, metaplastic and premalignant (i.e. mild,
      moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to
      evaluate whether differences in the apoptotic activity could already be seen in
      the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells
      and bodies were visualized by 3' end labelling. The expression of p53 and members
      of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined
      immunohistochemically with specific antibodies. The relative number of apoptotic
      cells and bodies [apoptotic index (AI%)] was already increased threefold as the
      normal bronchial epithelium changed to squamous metaplasia, and the AIs of the
      dysplastic lesions were about four times higher than those of the normal
      epithelium. Apoptosis was significantly associated with cell proliferation, as
      determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry.
      However, the extent of apoptosis did not correlate with the expression of p53,
      bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma
      sequence in the lung, the elevation of the AI% is an early event associated with
      cell proliferation activity, but is independent of the expression of p53, bcl-2,
      mcl-1 and bax.

PMID- 10070904
TI  - Peritoneal dialysis: the state of the art in Europe.

PMID- 10070905
TI  - Plasmapheresis as the sole therapy for rapidly progressive Henoch-Schonlein
      purpura nephritis in children.
AB  - To clarify the therapeutic role of plasmapheresis (PP) for patients with Henoch
      Schonlein purpura (HSP) nephritis, the clinical courses of nine children with a
      rapidly progressive type of HSP nephritis, who were treated with PP as the sole
      therapy, were retrospectively evaluated. All patients had nephrotic-range
      proteinuria (4.9 +/- 2.5 g/m2/d, mean +/- SD) and decreased glomerular filtration
      rate (GFR) (46.5 +/- 9.5 mL/min/1.73 m2) at the time of the initiation of PP.
      Biopsy specimens taken before PP showed large crescents involving more than 50%
      of the glomerular circumference in 56.8 +/- 6.9% of the glomeruli examined. The
      mean interval between disease onset and initiation of PP was 39.1 +/- 22.1 days.
      The PP regimen consisted of thrice-weekly treatment for 2 weeks, then weekly
      treatment for 6 weeks. No patients received any steroids or cytotoxic drugs,
      except for the use of steroids to manage severe abdominal pain. All patients
      responded promptly to PP with improvement in renal function, reduction of
      proteinuria, and subsidence of purpuric rash and abdominal pain. Six of nine
      patients showed further improvements without any other treatments; four had
      complete recovery, and two had only microscopic hematuria at the latest
      observation (follow-up period, 9.6 +/- 4.3 years). The remaining three patients
      showed a rebound increase of proteinuria after completion of PP; two of whom
      progressed to end-stage renal failure at 14.1 years and 1.8 years after disease
      onset. Because all patients had the most severe forms of nephritis, reported to
      carry a grave prognosis, this study suggests that PP as the sole therapy is
      effective in improving the prognosis of patients with rapidly progressive HSP
      nephritis, particularly if instituted early in the course of the disease. The
      role of PP in treating HSP nephritis deserves to be assessed further in larger
      randomized controlled trials.

PMID- 10070906
TI  - Expression of interferon-inducible Mx-proteins in patients with IgA nephropathy
      or Henoch-Schonlein purpura.
AB  - Both viral infections and dysregulated cytokine synthesis have been implicated in
      the pathogenesis of immunoglobulin A nephropathy (IgAN) and Henoch-Schonlein
      purpura (HSP). Mx proteins are specifically induced by type I interferons (IFN
      alpha, -beta, -omega) and are very sensitive in detecting, for example, virus
      induced, in vivo production of IFN-alpha/-beta, because the biological half-life
      of Mx (approximately 3 days) markedly exceeds that of IFN-alpha/-beta (20 to 90
      minutes). Mx concentrations in leukocytes were measured by enzyme-linked
      immunosorbent assay (ELISA) in 79 blood samples of 35 patients with IgAN and five
      with HSP. No patient showed symptoms of infections at the time of the
      examination. Compared with normal leukocyte Mx concentrations (<2 mU/1,000
      leukocytes), only 3 of 79 samples of IgAN/HSP patients showed mildly elevated Mx
      concentrations (range, 2.2 to 3 mU/1,000 leukocytes). By contrast, patients with
      increased endogenous IFN production (lupus erythematosus) or patients treated
      with IFN-alpha2 showed leukocyte Mx concentrations of up to 35 mU/1,000
      leukocytes. In patients with IgAN and HSP, leukocyte Mx concentrations were not
      correlated with various clinical parameters. Immunohistochemically, no renal Mx
      expression could be detected in eight renal biopsy specimens of patients with
      various stages of IgAN, whereas control specimens (skin of patients treated with
      IFN-alpha2) showed abundant cellular Mx expression. Furthermore, human mesangial
      cells in vitro showed marked Mx production after exposure to IFN-alpha or IFN
      beta. We conclude that, in patients with IgAN/HSP, no evidence of an activation
      or dysregulation of the type I interferon system can be detected.

PMID- 10070907
TI  - Renal manifestations of concurrent systemic lupus erythematosus and HIV
      infection.
AB  - Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection,
      yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen
      concurrently in the same patient. Many of the cases of combined HIV infection and
      SLE reported in the literature are patients with SLE before HIV infection and who
      did not undergo renal biopsy at a time when both processes were present. We
      report the clinical manifestations and renal biopsy findings in four subjects
      with concurrent HIV infection and SLE and compare them with the seven previously
      reported cases in the literature. Taken together, most patients were black (91%)
      and male (73%), and approximately half (55%) were children with perinatal HIV
      infection. These demographics differ markedly from those of idiopathic SLE, a
      disease that predominantly affects female adults. Renal presentations included
      proteinuria and hypocomplementemia, frequently with hematuria and renal
      insufficiency. Renal biopsy findings in 10 cases included all classes of lupus
      nephritis (class IIb in two cases, class III in one case, class IV in three
      cases, class V in three cases, class III and V in one case), two of which also
      displayed overlapping features of HIV-associated nephropathy (HIVAN). One case
      had isolated findings of HIVAN. This cohort provides a unique population in which
      to study interacting pathomechanisms between HIV infection and SLE.

PMID- 10070908
TI  - A subdepressor low dose of ramipril lowers urinary protein excretion without
      increasing plasma potassium.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are increasingly administered to
      patients with chronic renal disease. One issue of concern with the use of ACE
      inhibitors in patients with impaired renal function is the possible development
      of hyperkalemia. We reasoned that the impact of ACE inhibitors on plasma
      potassium could be minimized by administering these agents at very low doses. To
      examine this issue, we investigated the effect of a low dose of ramipril (1.25 mg
      orally once daily) and an eight-fold higher dose (10 mg orally once daily) on
      plasma potassium in 13 patients with proteinuria and mild chronic renal
      insufficiency. The study was divided into four phases: placebo (4 weeks), low
      dose ramipril (8 weeks), high-dose ramipril (8 weeks), and washout phase (4
      weeks). With the low dose of ramipril, urinary protein excretion decreased
      significantly as early as after 1 week of administration (from 4.4 +/- 0.5 to 3.7
      +/- 0.4 g/24 h; P < 0.025) and did not decrease any further thereafter even when
      the dose was increased eight-fold. Mean arterial blood pressure and plasma
      potassium did not change significantly with the low dose of ramipril, whereas
      with the higher dose, mean arterial blood pressure decreased significantly (from
      107 +/- 2.0 to 100 +/- 2.0 mm Hg, P < 0.005), and plasma potassium increased
      significantly (from 4.53 to 4.78 mEq/L, P < 0.05). We conclude that a low dose of
      ramipril can reduce proteinuria to the same extent as an eight-fold higher dose
      without significantly lowering blood pressure or increasing plasma potassium.
      This latter feature may be advantageous for the treatment of patients at risk for
      hyperkalemia who require ACE inhibitors.

PMID- 10070909
TI  - Urinary protein excretion and serum tumor necrosis factor in diabetic patients
      with advanced renal failure: effects of pentoxifylline administration.
AB  - In 24 diabetic patients with advanced renal failure (creatinine clearance [C(Cr)]
      < 35 mL/min), we prospectively studied serum tumor necrosis factor-alpha (TNF
      alpha) levels, the possible relationship with urinary protein excretion, and the
      effects of pentoxifylline (PTF) administration. PTF (400 mg daily) was
      administered for 6 months to 14 patients, and the results were compared with data
      from a control group (n = 10). Baseline parameters were similar in both groups.
      At the end of the study, urinary protein excretion and serum TNF-alpha decreased
      in the active group from 2.7 (1.2 to 5.8) g/d and 569 +/- 285 pg/mL to 1.1 (0.3
      to 4.0) g/d and 329 +/- 232 pg/mL, respectively (P < 0.001). By contrast,
      proteinuria and TNF-alpha did not change in the control group. Regression
      analysis showed a significant correlation between proteinuria and serum TNF-alpha
      both at basal (r = 0.55) and at the sixth month (r = 0.57). Furthermore, the
      reduction of urinary protein excretion was strongly correlated with the decrease
      of TNF-alpha (r = 0.72, P < 0.01). Serum Cr and C(Cr) remained stable in both
      groups during the study. Our findings suggest that cytokines might play a role in
      renal damage in diabetic nephropathy. PTF is effective in reducing proteinuria in
      diabetic patients with advanced renal failure. The anticytokine activity of PTF
      may be a further explanation for this antiproteinuric effect.

PMID- 10070910
TI  - Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than
      iron dextrans.
AB  - Use of recombinant human erythropoietin in patients with end-stage renal disease
      has highlighted iron deficiency as the major cause of resistant anemia. The
      current mainstay of intravenous (i.v.) iron replacement therapy, iron dextran,
      has been shown in prior studies to have a risk of serious life-threatening
      anaphylaxis of just under 1 per 100 patients exposed. The current study assessed
      the safety profile of an alternative i.v. iron, sodium ferric gluconate complex
      in sucrose (Ferrlecit), as compared with iron dextrans. Sodium ferric gluconate
      complex in sucrose, a unique chemical preparation, has been in use since 1959,
      principally in Europe, at a rate of approximately 2.7 million i.v. doses per year
      (1992 to 1996) in Germany and Italy alone. For iron dextran, usage in the United
      States was comparable--principally renal hemodialysis--and estimated from market
      sources at 3.0 million doses per year (1995). From 1976 to 1996, there were 74
      allergic adverse events reported for sodium ferric gluconate complex in sucrose
      to the World Health Organization (WHO), German Health Bureau, and the
      manufacturer (all combined). For the years 1992 to 1996, sodium ferric gluconate
      complex in sucrose had an allergy event reporting rate of 3.3 allergy episodes
      per million doses per year compared with a similar rate of 8.7 reported allergy
      events per million doses per year for iron dextran in the United States in 1995.
      Case fatalities for sodium ferric gluconate complex in sucrose and iron dextran
      within these reports were then compared. For sodium ferric gluconate complex in
      sucrose, there were no reports of deaths over the entire period (1976 to 1996).
      However, for iron dextrans, there were 31 fatalities among 196
      allergy/anaphylaxis cases reported in the United States between 1976 and 1996,
      yielding a case-fatality rate of 15.8%. These data show that sodium ferric
      gluconate complex in sucrose, when compared with iron dextrans in comparably
      sized patient usage populations with similar total rates of reporting of allergic
      events, has a significantly lower reported mortality rate (P < 0.001). Thus, the
      data justify usage of sodium ferric gluconate complex in sucrose as the safer
      iron replacement therapeutic agent.

PMID- 10070911
TI  - Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis
      patients: North American Clinical Trial.
AB  - A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in
      sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered
      over 8 consecutive dialysis days in equally divided doses to a total of either
      0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of
      anemic, iron-deficient hemodialysis patients receiving recombinant human
      erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and
      hematocrit and changes of iron parameters. Results were compared with
      historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g
      sodium ferric gluconate complex in sucrose resulted in significantly greater
      improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all
      time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment.
      Despite an initial improvement in mean serum ferritin and transferrin saturation,
      500 mg i.v. therapy did not result in a significant improvement in hemoglobin at
      any time. Eighty-three of 88 patients completed treatment with sodium ferric
      gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group.
      Two patients discontinued for personal reasons. The other three discontinued
      because of a rash, nausea and rash, and chest pain with pruritus, respectively.
      In comparison with 25 matched control patients, adverse events could not be
      linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric
      gluconate complex in sucrose is safe and effective in the management of iron
      deficiency anemia in severely iron-deficient and anemic hemodialysis patients
      receiving rHuEPO. This study confirms the concepts regarding iron therapy
      expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative
      (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or
      transferrin saturations below 18% need supplementation with parenteral iron in
      excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.

PMID- 10070912
TI  - Transplantation, not dialysis, corrects azotemia-dependent priming of the
      neutrophil oxidative burst.
AB  - The oxidative burst of neutrophils from patients with renal failure before the
      initiation of dialysis is primed for an enhanced response after stimulation by
      phagocytosis or chemoattractants. This study shows that phagocytosis-stimulated
      oxidative burst activity remains primed in patients treated with both high
      efficiency hemodialysis and continuous ambulatory peritoneal dialysis (CAPD), but
      it is normal in patients with a functioning renal transplant. Incubation of
      normal neutrophils or HL-60 granulocytes in azotemic plasma results in increased
      resting and phagocytosis-stimulated H2O2 production, which is rapidly reversible
      on removal of the plasma. Priming of the oxidative burst by azotemic plasma is
      independent of changes in opsonization and phagocytosis and does not require
      protein synthesis. These results suggest that azotemic plasma contains a
      substance or substances capable of reversibly priming oxidative burst activity in
      neutrophils and neutrophil-like cell lines. The Inability of high-efficiency
      hemodialysis and CAPD to normalize oxidative burst activity suggests that this
      substance is of higher molecular weight.

PMID- 10070913
TI  - Folate measurements in patients on regular hemodialysis treatment.
AB  - Patients on regular hemodialysis treatment may develop megaloblastic anemia
      caused by folate deficiency, but whether folate supplementation is required is
      still controversial, particularly during erythropoietin administration.
      Erythrocyte folate concentration is a better indicator of folate status than
      serum folate, although the latter is the variable generally measured. We measured
      serum and erythrocyte folate in blood samples from 112 regular hemodialysis
      patients (57 men, 55 women, 50 treated with erythropoietin, and 62 not) by
      Stratus Folate immunoenzymatic assay (Dade). Patients with very low serum (<2.87
      ng/mL) but normal erythrocyte folate were reinvestigated 4 months later without
      receiving folate supplementation meanwhile. Serum folate concentrations were 0.48
      to 12.76 ng/mL (median, 3.40) and erythrocyte folate 0.19 to 1.85 microg/mL
      (median, 0.42). Only 37% serum folate values were in the relevant reference
      interval compared with 80.2% erythrocyte folate values (3.08 to 17.65 ng/mL and
      0.24 to 0.64 microg/mL, respectively). A significant correlation was found
      between serum and erythrocyte folate concentrations, without clinical relevance
      caused by the wide scatter around the regression line. Serum and erythrocyte
      folate did not vary significantly between patients given erythropoietin and those
      not so treated. The folate status of the 24 patients with very low serum folate
      was almost unchanged 4 months later. According to the serum folate test, 63% of
      patients needed folate supplementation, whereas the erythrocyte folate test, a
      better indicator of folate status, suggested that only 1.8% of patients needed
      folate supplementation. Erythropoietin therapy appears not to be an indication
      for standard folate supplementation in hemodialysis patients.

PMID- 10070914
TI  - Factors associated with inadequate blood pressure control in hypertensive
      hemodialysis patients.
AB  - Hypertension is common in hemodialysis patients and increases cardiovascular
      morbidity and mortality. We determined the prevalence of inadequate control of
      hypertension in 489 patients receiving hemodialysis and identified factors
      associated with uncontrolled hypertension. We interviewed the patients and
      abstracted demographic and clinical information from a computerized database. The
      prevalence of uncontrolled hypertension (average predialysis blood pressure, > or
      =160/90 mm Hg) was 62%. Ninety-one percent of patients with uncontrolled
      hypertension were receiving submaximal antihypertensive drug therapy, and 59%
      withheld their medications before dialysis. Uncontrolled hypertensives had a
      greater interdialytic weight gain (3.8% v 3.5%, P = 0.07) and a greater excess
      weight gain (3.1 +/- 1.6 kg v 2.5 +/- 1.4 kg; P < 0.05) compared with controlled
      hypertensives. Patients with uncontrolled hypertension showed higher
      interdialytic weight gain (2.7 +/- 0.06 kg v 2.2 +/- 0.13 kg; P < 0.05), were
      more likely to be black (94% v 81%; P < 0.05), were more likely to have
      hypertension as the cause of their end-stage renal disease (ESRD) (42% v 24%; P <
      0.05), and had been receiving hemodialysis for a shorter time (4.3 +/- 2 yr v 6.1
      +/- 0.9 yr; P < 0.05) compared with normotensive patients. There was significant
      correlation between diastolic blood pressure and both interdialytic weight gain
      (r = 0.31, P < 0.05) and percent weight gain (r = 0.34, P < 0.05) in the
      hypertensive but not in the normotensive patients (r = -0.21). Interdialytic
      weight gain and hypertension as a cause of ESRD were independent predictors of
      predialysis systolic blood pressure. We conclude that hypertension is
      uncontrolled in most patients undergoing hemodialysis. Submaximal
      antihypertensive therapy, excessive interdialytic weight gain, and withholding
      antihypertensive medication before dialysis are correctable factors potentially
      contributing to uncontrolled hypertension.

PMID- 10070915
TI  - Predialysis blood pressure and mortality risk in a national sample of maintenance
      hemodialysis patients.
AB  - The role of predialysis blood pressure (BP) as a risk factor for the high
      mortality in chronic hemodialysis (HD) patients has remained controversial. The
      objective of the current study was to further explore in a national random sample
      of 4,499 US hemodialysis patients any relationship of systolic or diastolic and
      predialysis or postdialysis BP with mortality, while considering subgroups of
      patients and controlling for other patient characteristics and comorbidities. The
      main finding of this study is the association of a low predialysis systolic BP
      with an elevated adjusted mortality risk (relative mortality risk [RR] = 1.86 for
      systolic BP < 110, P < 0.0001). No association with an elevated mortality risk
      could be observed for predialysis systolic hypertension (RR = 0.98 to 0.99, not
      significant [NS]), except for an elevated risk of cerebrovascular deaths.
      Postdialysis systolic BP was associated with an elevated mortality risk both for
      low and high BP levels as compared with midrange BP. Further evaluation of the
      elevated mortality risk associated with low predialysis systolic BP indicated
      similar patterns for both diabetic and nondiabetic subgroups and for patients
      with and without congestive heart failure (CHF) or coronary artery disease,
      although it was more pronounced among those with CHF. The level of predialysis
      fluid excess did not modify these results substantially. The findings from this
      historical prospective national study do not argue against the treatment of
      hypertension and suggest greater attention to postdialysis hypertension. The
      strikingly elevated mortality risk with low predialysis systolic BP suggests that
      low predialysis BP needs to be viewed with great concern and avoided where
      possible.

PMID- 10070916
TI  - Natural logarithmic estimates of Kt/V in the pediatric hemodialysis population.
AB  - The natural logarithm formula for Kt/V proposed by Daugirdas is recognized as a
      valid and simple alternative to formal urea kinetic modeling (UKM) in adults
      receiving hemodialysis. No data have been published to validate the use of this
      formula in infants, children, and adolescents. We compared Kt/V derived by formal
      UKM with the natural logarithmic formula for 103 treatments in 21 pediatric end
      stage renal disease patients receiving chronic hemodialysis. Values for Kt/V
      derived by formal UKM ranged from 0.65 to 2.06. Patients ranged in age from 1.8
      to 22.5 years and in dry weight from 10.2 to 82.5 kg. The largest percent error
      between the two methods for any data point was less than 6%. The total error
      (absolute value percent error + 2 SD) was less than 6% across the entire range of
      dry weights. Our data show excellent agreement between formal UKM and the natural
      logarithm formula for Kt/V in pediatric hemodialysis patients, even those
      weighing less than 30 kg. These results support the use of the natural logarithm
      formula as a valid alternative to formal UKM in children. The simplicity of this
      formula should allow for the use of Kt/V as the best measure to study the
      relationship between delivered dialysis dose and outcomes in children.

PMID- 10070917
TI  - Associates of mortality among peritoneal dialysis patients with special reference
      to peritoneal transport rates and solute clearance.
AB  - The current report describes the distributions of selected demographic and
      biochemical parameters, clearance, and other transport values among patients
      undergoing peritoneal dialysis (PD) and evaluates the associates of mortality
      using those values, with and without clearance and peritoneal equilibration test
      (PET) data. All patients receiving PD on January 1, 1994 were selected (n =
      2,686). Patients who switched to another form of dialysis during the study period
      were removed from the study at the time of therapy change. Working files were
      constructed from the clinical database to include demographic, laboratory, and
      outcome data. Laboratory data were available in only 1,603 patients and were used
      to evaluate the biochemical associates of mortality after merging the
      biochemical, demographic, and outcome data. Patients with clearance data or PET
      studies underwent a second analysis to assess the effects of peritoneal and renal
      clearance on survival. The analysis of demographic and laboratory data confirmed
      the importance of age and serum albumin concentration as predictors of death.
      Residual renal function (RRF) was strongly correlated with survival, but
      peritoneal clearance was not. Several possible explanations for the lack of
      correlation between peritoneal clearance and survival are discussed. The data
      suggest that RRF and peritoneal clearance may be separate and not equivalent
      quantities. Substantial work is required to confirm or refute these findings,
      because the information is essential to establish the adequate dose of PD in
      patients with various degrees of RRF.

PMID- 10070918
TI  - Comparison of double-bag and Y-set disconnect systems in continuous ambulatory
      peritoneal dialysis: a randomized prospective multicenter study.
AB  - We performed a multicenter, single-blinded, prospective randomized study on the
      use of a double-bag disconnect system (B) versus a Y-set disconnect system (Y).
      The peritonitis rate, exit site infection, clinical outcome, and patients'
      acceptance to the procedure were assessed. A total of 120 new end-stage renal
      failure patients of three regional hospitals were randomized: 60 each to the B
      and the Y systems. The results of 60 patients on the B system and 51 on the Y
      system were analyzable. They were followed up for a median of 16 months.
      Peritonitis rates for the B and the Y systems were 33.5 and 29.4 patient-months
      per episode, respectively. Exit site infection rates for the B and Y systems were
      17.4 and 16.0 patient-months per episode, respectively. Four catheters were
      removed in each group. Patients on the B system were hospitalized for 2.1 days
      per patient per year related to peritonitis and exit site infection, and those on
      the Y system were hospitalized for 1.2 days. There was no significant difference
      between the B and Y systems in the incidences of peritonitis (all causes and
      those due to coagulase-negative staphylococci), exit site infection, and in
      hospitalization days. However, there was a higher percentage of gram-positive
      infections in the Y system (52%) than in the B system (32%) and a lower
      percentage of gram-negative infections in the Y system (16%) than in the B system
      (32%). Patients on the B system had a better acceptance of the procedure than
      patients on the Y system, as assessed by a six-item, 10-point questionnaire
      (total score, 43.1 +/- 10.2 v 37.6 +/- 9.4; P < 0.005 at 1 month; 44.6 +/- 9.1 v
      39.8 +/- 8.6; P < 0.01 at 6 months). From this study, it is concluded that the B
      and Y systems are similar in the incidences of peritonitis and exit site
      infection, although the B system is better accepted by patients. This is probably
      the first multicenter randomized study comparing the double-bag and Y-set
      disconnect system using only new patients who had never used other systems of
      continuous ambulatory peritoneal dialysis.

PMID- 10070919
TI  - Normal function and lack of fibronectin accumulation in kidneys of Clara cell
      secretory protein/uteroglobin deficient mice.
AB  - Clara cell secretory protein (CCSP), also known as uteroglobin (Ug), is a 16-kDa
      homodimeric protein of unknown function. Within rodent species, CCSP is expressed
      predominantly by nonciliated Clara cells that line conducting airways of the
      lung. To investigate in vivo functions for CCSP, we established mice homozygous
      for a null allele of the CCSP gene (CCSP-/-). We previously showed no overt
      phenotypic consequences associated with CCSP deficiency when CCSP-/- mice are
      maintained in the absence of environmental stress. However, CCSP-/- mice show an
      oxidant-sensitive phenotype that cannot be attributed to alterations in the
      inflammatory response when challenged by inhaled oxidant gases. The current study
      was undertaken to determine whether CCSP deficiency results in pathological
      changes to the kidney. This study was prompted by the recent description of
      severe systemic disease and kidney fibrosis/dysfunction in an independent line of
      CCSP-deficient mice, termed Ug-/- (Zhang et al, Science 276:1408-1412, 1997).
      CCSP-/- mice show normal growth and reproductive performance when maintained in
      two independent genetic backgrounds, inbred 129 and congenic C57BL/6. Strain 129
      CCSP-/- mice have normal kidney function, as assessed by urinary glucose, lactate
      dehydrogenase, and glomerular filtration rate; they show no kidney fibrosis or
      abnormalities in fibronectin accumulation and no histological abnormalities in
      proximal convoluted tubules or glomeruli at either light or electron microscopic
      levels. CCSP deficiency is associated with mild proteinurea involving a modest
      increase in mouse major urinary protein-1. We conclude that CCSP (Ug) deficiency,
      per se, is not the cause of severe renal pathology and systemic disease reported
      for Ug-/- mice.

PMID- 10070920
TI  - Biopsy-proven resolution of immune complex-mediated crescentic glomerulonephritis
      with mycophenolate mofetil therapy in an allograft.
AB  - We report biopsy-proven resolution of immune-complex-mediated crescentic
      glomerulonephritis (ICMCGn) using mycophenolate mofetil (MMF). Therapy with
      steroids and cyclophosphamide failed twice in a 39-year-old white man who
      developed ICMCGn in his native kidneys, and subsequently in a human lymphocyte
      antigen-identical renal allograft. When he developed ICMCGn in a second, now
      cadaver, allograft, he was treated with steroids and MMF instead. His serum
      creatinine (Cr) improved from 4.4 mg/dL to 2.1 mg/dL. A biopsy 21 months later
      showed him to be free of glomerular disease. MMF is known to be an effective
      immunosuppressant. In our patient, ICMCGn, a notoriously difficult entity to
      treat effectively, seemingly resolved with MMF therapy. We suggest that MMF may
      be effective in the treatment of immunologically mediated pre-end-stage renal
      disease (ESRD). It should be considered in any posttransplantation setting where
      the original cause of organ failure is known to be immunologically mediated and
      likely to recur.

PMID- 10070921
TI  - Thrombotic microangiopathy as a complication of long-term therapy with
      gemcitabine.
AB  - Three patients with pancreatic carcinoma treated with gemcitabine for 1 year
      developed clinical and laboratory findings compatible with an indolent form of
      the hemolytic-uremic syndrome. Renal biopsy specimens in two of these patients
      showed the characteristic features of thrombotic microangiopathy, and a skin
      biopsy specimen from the third patient, who presented with livedo reticularis,
      showed intravascular fibrin deposition. Thrombotic microangiopathy may represent
      a toxic effect of long-term gemcitabine therapy.

PMID- 10070922
TI  - Fatal cervical spondyloarthropathy in a hemodialysis patient with systemic
      deposition of beta2-microglobulin amyloid.
AB  - Destructive spondyloarthropathy is a serious complication in patients with end
      stage renal disease. We report a case of fatal cervical spondyloarthropathy in a
      patient on hemodialysis who presented with severe pain in the cervical area.
      Magnetic resonance imaging (MRI) of the cervical spine showed a soft tissue mass
      at the cervico-occipital hinge with spinal cord compression and destructive
      lesions of the cervical vertebrae. The patient became quadriplegic during the MRI
      procedure and died a few days later. Postmortem examination showed deposition of
      beta2-microglobulin in the cervico-occipital hinge. A unique feature of this case
      was the documented presence of systemic beta2-microglobulin amyloid deposits
      involving the spleen that to our knowledge has not been reported previously.
      Clinical suspicion and early detection of lesions caused by dialysis-related
      amyloidosis (DRA) may help to prevent significant morbidity and mortality in long
      term dialysis patients.

PMID- 10070923
TI  - Optimal care of the pediatric end-stage renal disease patient on dialysis.
AB  - This manuscript is an effort on behalf of the American Society of Pediatric
      Nephrology to provide recommendations designed to optimize the clinical care of
      pediatric patients with end-stage renal disease (ESRD). Although many of the
      recommendations are evidenced-based with the supporting data being derived from a
      variety of sources, including patient registries, others are opinion-based and
      derived from the combined clinical experience of the authors. In all cases, it is
      recommended that the decision to initiate dialysis should be made only after an
      assessment of a combination of biochemical and clinical characteristics.
      Irrespective of the choice of dialysis modality (hemodialysis v peritoneal
      dialysis), dialysis efficacy should be measured regularly, and the dialysis
      prescription should be designed to achieve target clearances. Attention to
      dialysis adequacy, control of osteodystrophy, nutrition, and correction of anemia
      is mandatory, because all may influence patient outcome in terms of growth,
      cognitive development, and school performance. Finally, the availability of a
      multidisciplinary team of pediatric specialists is desirable to provide all
      facets of pediatric ESRD care, including renal transplantation, in an optimal
      manner. Future clinical research efforts intended to address topics such as
      dialysis adequacy, anemia management, and growth should be encouraged.

PMID- 10070924
TI  - Relationship between urea reduction ratio, demographic characteristics, and body
      weight for patients in the 1996 National ESRD Core Indicators Project.
AB  - The 1996 Health Care Financing Administration's (HCFA) Core Indicators Project
      for in-center, hemodialysis patients collects information on the quality of care
      delivered in four clinical areas that were anticipated to predict patient
      outcomes. Included among these clinical performance measurements is the delivered
      dose of hemodialysis, measured by the fractional reduction of urea achieved
      during a single hemodialysis session (urea reduction ratio [URR]). A random
      sample (N = 7,310) of adult (aged > or =18 years), in-center hemodialysis
      patients was selected, and a one-page data collection form for each patient was
      sent to the dialysis facility in which care was provided during the last quarter
      of 1995. The dialysis facilities provided information for 6,861 (94%) patients,
      and at least one paired predialysis and postdialysis blood urea nitrogen (BUN)
      concentration was reported for 6,655 (97%) of these patients. The URR of this
      cohort was 65.5% +/- 8.0% (mean +/- SD), and 41% of patients had a URR less than
      65%. The mean dialysis session length was 203 minutes, and more than half of the
      patients received dialysis with a dialyzer membrane with a KUf less than 10 mL/mm
      Hg/h. The patients with a URR less than 65% had a mean body weight approximately
      10 kg greater than patients with a URR of 65% or greater. This relationship was
      present for all demographic characteristics studied, including age, gender, race,
      and primary cause of end-stage renal disease (ESRD). Patients receiving dialysis
      for less than 6 months were more likely to have a URR less than 65% than patients
      on dialysis for longer periods. By multivariate analysis, variables significantly
      associated with a delivered URR less than 65% were body weight in the heaviest
      quartile (odds ratio [OR] = 6.1), male gender (OR = 2.6), on dialysis therapy
      less than 6 months (OR = 2.5), youngest quartile of age (<49 years) (OR = 2.0),
      lowest quartile of serum albumin values less than 3.6 g/dL (bromcresol green
      method) or less than 3.3 g/dL (bromcresol purple method) (OR = 1.6), black (OR =
      1.5), dialyzed with a dialyzer KUf less than 20 mL/mm Hg/h (OR = 1.8), lowest
      quartile hematocrit (<29.7%) (OR = 1.2), and shorter dialysis session length (OR
      = 1.02/min). In conclusion, both patient-specific demographic variables and
      treatment-specific parameters are significantly associated with ESRD patients
      receiving a URR less than 65%. Furthermore, these data suggest statistically
      significant linkages between the delivered dose of hemodialysis and other
      independent outcome predictors such as serum albumin concentration. Prospective
      study is required to determine whether intervention strategies to improve the
      delivered dose of hemodialysis will affect this outcome predictor or whether
      serum albumin and dialysis dose share a common cause not amenable to increasing
      the URR.

PMID- 10070925
TI  - Hypertension in the hemodialysis population? High time for answers.

PMID- 10070926
TI  - Intravenous iron supplementation in end-stage renal disease patients.

PMID- 10070927
TI  - Advantages and pitfalls of transgenic and mutant animals.

PMID- 10070928
TI  - To be or not to be: the decision to withdraw or be withdrawn from dialysis.

PMID- 10070929
TI  - Nephrotic range proteinuria and hematuria in a white bisexual male.

PMID- 10070930
TI  - Treatment of renal artery stenosis by invasive procedures.

PMID- 10070931
TI  - Ringer's lactate: an inexpensive and effective dialysate for continuous renal
      replacement therapy.

PMID- 10070932
TI  - Colorectal cancer screening: sifting through the evidence.

PMID- 10070933
TI  - Searching for evidence of altered gene expression: a comment on statistical
      analysis of microarray data.

PMID- 10070934
TI  - As easy as ABC: scientists fish out another drug resistance gene.

PMID- 10070935
TI  - Treating the most intractable cancers progresses slowly.

PMID- 10070936
TI  - Panel finds in utero gene therapy proposal is premature.

PMID- 10070937
TI  - Designing ways: computer animators illustrate cancer research in 3-D imagery.

PMID- 10070938
TI  - How to divvy up NIH's research pie sparks debate.

PMID- 10070939
TI  - NCAB passes resolution on access to grantee data. National Cancer Advisory Board.

PMID- 10070940
TI  - Dietary fat and prostate cancer: current status.
AB  - Efforts to elucidate the causes of prostate cancer have met with little success
      to date. All that is known with certainty is that the incidence increases
      exponentially with age, varies by geography and by race or ethnicity, and is
      higher among men whose father or brother had the disease. Because the incidence
      changes in migrants and their offspring, exogenous factors certainly contribute
      to the risk of prostate cancer. Early epidemiologic studies implicated dietary
      fat as a likely causal factor for this cancer. However, scientific support for
      such an association has diminished in recent years as more epidemiologic evidence
      has accrued. Accordingly, we reviewed the relevant English language literature on
      this topic, including epidemiologic and animal studies, as well as current
      concepts regarding the involvement of fat in carcinogenesis to re-examine the fat
      prostate cancer hypothesis. We conclude that dietary fat may indeed be related to
      prostate cancer risk, although the specific fat components that are responsible
      are not yet clear. Given the diverse effects of fatty acids on cellular biology
      and chemistry, it seems likely that the relationship is complex, involving the
      interplay of fat with other dietary factors, such as antioxidant vitamins and
      minerals, or with genetic factors that influence susceptibility. Some suggestions
      for further research are offered.

PMID- 10070941
TI  - Atypical multidrug resistance: breast cancer resistance protein messenger RNA
      expression in mitoxantrone-selected cell lines.
AB  - BACKGROUND: Human cancer cell lines grown in the presence of the cytotoxic agent
      mitoxantrone frequently develop resistance associated with a reduction in
      intracellular drug accumulation without increased expression of the known drug
      resistance transporters P-glycoprotein and multidrug resistance protein (also
      known as multidrug resistance-associated protein). Breast cancer resistance
      protein (BCRP) is a recently described adenosine triphosphate-binding cassette
      transporter associated with resistance to mitoxantrone and anthracyclines. This
      study was undertaken to test the prevalence of BCRP overexpression in cell lines
      selected for growth in the presence of mitoxantrone. METHODS: Total cellular RNA
      or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell
      lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene
      were analyzed by northern and Southern blot hybridization, respectively. RESULTS:
      A variety of drug-resistant human cancer cell lines derived by selection with
      mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines
      of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric
      carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins.
      Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that
      the BCRP gene was also amplified in these cells. CONCLUSIONS: Overexpression of
      BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with
      mitoxantrone, suggesting that BCRP is likely to be a major cellular defense
      mechanism elicited in response to exposure to this drug. It is likely that BCRP
      is the putative "mitoxantrone transporter" hypothesized to be present in these
      cell lines.

PMID- 10070942
TI  - Colorectal cancer mortality: effectiveness of biennial screening for fecal occult
      blood.
AB  - BACKGROUND: In 1993, a randomized controlled trial in Minnesota showed, after 13
      years of follow-up, that annual fecal occult blood testing was effective in
      reducing colorectal cancer mortality by at least 33%. Biennial screening (i.e.,
      every 2 years) resulted in only a 6% mortality reduction. Two European trials (in
      England and in Denmark) subsequently showed statistically significant 15% and 18%
      mortality reductions with biennial screening. Herein, we provide updated results
      through 18 years of follow-up--from the Minnesota trial that address the apparent
      inconsistent findings among the trials regarding biennial screening. METHODS:
      From 1976 through 1977, a total of 46551 study subjects, aged 50-80 years, were
      recruited and randomly assigned to an annual screen, a biennial screen, or a
      control group. A screen consisted of six guaiac-impregnated fecal occult blood
      tests (Hemoccult) prepared in pairs from each of three consecutive fecal samples.
      Participants with at least one of the six tests that were positive were invited
      for a diagnostic examination that included colonoscopy. All participants were
      followed annually to ascertain incident colorectal cancers and deaths. RESULTS:
      The numbers of deaths from all causes were similar among the three study groups.
      Cumulative 18-year colorectal cancer mortality was 33% lower in the annual group
      than in the control group (rate ratio, 0.67; 95% confidence interval [CI] = 0.51
      0.83). The biennial group had a 21% lower colorectal cancer mortality rate than
      the control group (rate ratio, 0.79; 95% CI = 0.62-0.97). A marked reduction was
      also noted in the incidence of Dukes' stage D cancers in both screened groups in
      comparison with the control group. CONCLUSION: The results from this study,
      together with the other two published randomized trials of fecal occult blood
      screening, are consistent in demonstrating a substantial, statistically
      significant reduction in colorectal cancer mortality from biennial screening.

PMID- 10070943
TI  - Effect of in situ retroviral interleukin-4 transfer on established intracranial
      tumors.
AB  - BACKGROUND: Current therapies for malignant gliomas remain largely ineffective.
      We have previously demonstrated that interleukin 4 (IL-4) exhibits
      antitumorigenic activity in athymic nude mice by promoting both eosinophil
      infiltration and inhibition of tumor angiogenesis (formation of new blood
      vessels). In this study, we investigated treatment of established rat C6 cell
      gliomas by retroviral delivery of IL-4 in situ. METHODS: Tumors grown
      subcutaneously in athymic nude mice or implanted intracranially in
      immunocompetent Wistar rats were implanted with ecotropic retrovirus (i.e., will
      replicate only in cells of closely related species) packaging cells (RPCs) that
      were transfected with a retroviral vector encoding mouse IL-4 (1C5 cells) or a
      control vector (SV cells). For the demonstration of the long-term effects of such
      treatment, C6 cells were also implanted into the contralateral hemisphere of the
      brains of rats previously treated with 1C5 RPCs. Tumor volume measurements and
      immunohistochemical analyses were performed. RESULTS: Implantation of 1C5 RPCs
      into subcutaneous C6 cell tumors resulted in tumor growth arrest that was
      associated with eosinophil infiltration and inhibition of angiogenesis. When 1C5
      RPCs were stereotactically implanted into established intracranial tumors in
      rats, tumor volumes were dramatically smaller than in control animals
      (approximately 1.8 mm3 versus 70-80 mm3, respectively) 7 days after treatment.
      All 1C5 RPC-treated rats survived to 106 days after C6 cell implantation (99 days
      after treatment; an arbitrary end point), whereas control rats had to be killed
      14 days after C6 cell implantation because of extensive tumor growth. Histologic
      analysis demonstrated that treated tumors were completely eradicated, and
      immunohistochemical analysis revealed an inhibition of tumor angiogenesis and
      infiltration by CD8+ cells and macrophages. C6 cells implanted contralaterally
      into the brains of long-term-surviving rats treated with 1C5 RPCs were also
      rapidly and completely rejected. CONCLUSIONS: Implantation of packaging cells
      producing IL-4 retrovirus leads to rapid eradication of rat C6 cell gliomas and
      provides sustained protection against further intracranial challenge.

PMID- 10070944
TI  - CDKN2A variants in a population-based sample of Queensland families with
      melanoma.
AB  - BACKGROUND: Mutations in the CDKN2A gene confer susceptibility to cutaneous
      malignant melanoma (CMM); however, the population incidence of such mutations is
      unknown. Polymorphisms in CDKN2A have also been described, but it is not known
      whether they influence melanoma risk. We investigated the association of CDKN2A
      mutations and polymorphisms with melanoma risk in a population-based sample of
      families ascertained through probands with melanoma. METHODS: The 482 Queensland,
      Australia, families in our sample were characterized previously as having high,
      intermediate, or low family risk of CMM. Unrelated individuals (n = 200
      families/individuals) drawn from the Australian Twin Registry served as control
      subjects. For individuals in the high-risk group, the entire CDKN2A gene coding
      region was screened for mutations by use of the polymerase chain reaction,
      agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization,
      and single-strand conformation polymorphism analysis. The intermediate- and low
      risk families and control subjects were analyzed by ASO hybridization for a total
      of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442,
      500, and 540. RESULTS: CDKN2A mutations were found only in the high-risk families
      (nine [10.3%] of 87). The prevalence of the Nt500G (guanosine) polymorphism
      increased linearly with increasing familial risk (two-sided P = .02) and was
      highest in the nine (primarily Celtic) families with CDKN2A mutations. After
      adjustment for ethnic origin, the relationship between risk group and the
      frequency of the Nt500G allele was weakened (P = .25); however, there was no
      relationship between ethnic origin and Nt500-polymorphism frequency among the
      control subjects. CONCLUSIONS: CDKN2A mutations are rare in this population
      (approximately 0.2% of all melanoma cases in Queensland) and appear to be
      associated with melanoma in only the most affected families. The Nt500G allele
      appears to be associated with familial risk, but this association probably
      reflects Celtic ancestry.

PMID- 10070945
TI  - Statistical analysis of array expression data as applied to the problem of
      tamoxifen resistance.
AB  - BACKGROUND: Although the emerging complementary DNA (cDNA) array technology holds
      great promise to discern complex patterns of gene expression, its novelty means
      that there are no well-established standards to guide analysis and interpretation
      of the data that it produces. We have used preliminary data generated with the
      CLONTECH Atlas human cDNA array to develop a practical approach to the
      statistical analysis of these data by studying changes in gene expression during
      the development of acquired tamoxifen resistance in breast cancer. METHODS: For
      hybridization to the array, we prepared RNA from MCF-7 human breast cell tumors,
      isolated from our athymic nude mouse xenograft model of acquired tamoxifen
      resistance during estrogen-stimulated, tamoxifen-sensitive, and tamoxifen
      resistant growth. Principal components analysis was used to identify genes with
      altered expression. RESULTS AND CONCLUSIONS: Principal components analysis
      yielded three principal components that are interpreted as 1) the average level
      of gene expression, 2) the difference between estrogen-stimulated gene expression
      and the average of tamoxifen-sensitive and tamoxifen-resistant gene expression,
      and 3) the difference between tamoxifen-sensitive and tamoxifen-resistant gene
      expression. A bivariate (second and third principal components) 99% prediction
      region was used to identify outlier genes that exhibit altered expression. Two
      representative outlier genes, erk-2 and HSF-1 (heat shock transcription factor
      1), were chosen for confirmatory study, and their predicted relative expression
      levels were confirmed in western blot analysis, suggesting that semiquantitative
      estimates are possible with array technology. IMPLICATIONS: Principal components
      analysis provides a useful and practical method to analyze gene expression data
      from a cDNA array. The method can identify broad patterns of expression
      alteration and, based on a small simulation study, will likely provide reasonable
      power to detect moderate-sized alterations in clinically relevant genes.

PMID- 10070946
TI  - Metabolites of a tobacco-specific carcinogen in urine from newborns.
AB  - BACKGROUND: Cigarette smoking during pregnancy can result in fetal exposure to
      carcinogens that are transferred from the mother via the placenta, but little
      information is available on fetal uptake of such compounds. We analyzed samples
      of the first urine from newborns whose mothers did or did not smoke cigarettes
      for the presence of metabolites of the potent tobacco-specific transplacental
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). METHODS: The
      urine was collected and analyzed for two metabolites of NNK, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL
      Gluc). Gas chromatography and nitrosamine-selective detection, with confirmation
      by mass spectrometry, were used in the analyses, which were performed without
      knowledge of the origin of the urine samples. RESULTS: NNAL-Gluc was detected in
      22 (71%) of 31 urine samples from newborns of mothers who smoked; NNAL was
      detected in four of these 31 urine samples. Neither compound was detected in the
      17 urine samples from newborns of mothers who did not smoke. The arithmetic mean
      level of NNAL plus NNAL-Gluc in the 27 newborns of smokers for which both
      analytes were quantified was 0.14 (95% confidence interval [CI] = 0.083-0.200)
      pmol/mL. The levels of NNAL plus NNAL-Gluc in the urine from these babies were
      statistically significantly higher than those in the urine from newborns of
      nonsmoking mothers (geometric means = 0.062 [95% CI = 0.035-0.110] and 0.010
      [considered as not detected; no confidence interval], respectively; two-sided
      P<.001). NNAL plus NNAL-Gluc levels in the 18 positive urine samples in which
      both analytes were quantified ranged from 0.045 to 0.400 pmol/mL, with an
      arithmetic mean level of 0.20 (95% CI = 0.14-0.26) pmol/mL, about 5%-10% of the
      levels of these compounds detected in the urine from adult smokers. CONCLUSIONS:
      Two metabolites of the tobacco-specific transplacental carcinogen NNK can be
      detected in the urine from newborns of mothers who smoked cigarettes during
      pregnancy.

PMID- 10070947
TI  - High seroprevalence of antibodies to human herpesvirus-8 in Egyptian children:
      evidence of nonsexual transmission.
AB  - BACKGROUND: In western countries, human herpesvirus-8 (HHV-8) appears to be
      transmitted mainly by sexual contact. To evaluate the role of other transmission
      routes, especially in developing countries, we estimated the seroprevalence of
      HHV-8 in Egyptian children, who, if seropositive, would have acquired the virus
      through a nonsexual route. METHODS: Sera from 196 children (<1-12 years of age),
      20 adolescents (13-20 years of age), and 30 young adults (21-25 years of age)
      attending a vaccination program in Alexandria, Egypt, were studied.
      Immunofluorescence assays were used to detect antibodies against HHV-8 lytic
      phase antigens (anti-lytic) and latent-phase antigens (anti-latent). Antibodies
      against Epstein-Barr virus viral cap antigen, cytomegalovirus, and HHV-6 were
      detected by enzyme-linked immunosorbent assays. Seroprevalence of these
      herpesviruses was calculated after stratifying the subjects by age. RESULTS: Anti
      lytic and anti-latent HHV-8 antibodies were detected in 44.7% and 8.5% of the
      study participants, respectively. The prevalence of anti-lytic antibodies tended
      to increase with age, exceeding 50% in children older than 6 years; once children
      reached the age of 10 years, the prevalence tended to stabilize. The
      seroprevalence of other herpesviruses tended to be higher than that of HHV-8,
      ranging from approximately 83% to more than 97% in the 9- to 12-year age group.
      One- to 3-year-old children had higher titers of antilytic HHV-8 antibodies than
      children in the other age groups. Anti-latent antibodies were more frequently
      detected in individuals with high anti-lytic antibody titers. CONCLUSIONS: HHV-8
      antibodies are highly prevalent in Egyptian children, suggesting that, in
      developing countries, HHV-8 infection may be acquired early in life through
      routes other than sexual transmission. The lower seroprevalence of HHV-8 relative
      to that of the other herpesviruses suggests that HHV-8 is less transmissible than
      other common herpesviruses.

PMID- 10070948
TI  - Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of
      BRCA1 mutations.
AB  - BACKGROUND: Breast carcinomas occurring in carriers of BRCA1 gene mutations may
      have a distinctly different pathway of molecular pathogenesis from those
      occurring in noncarriers. Data from murine models implicate loss of p53 (also
      known as TP53) gene function as a critical early event in the malignant
      transformation of cells with a BRCA1 mutation. Therefore, breast tumors from
      BRCA1 mutation carriers might be expected to exhibit a high frequency of p53
      mutations. This study examined the frequency of p53 mutations in the breast
      tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. METHODS:
      Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for
      mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain
      reaction and single-strand conformation polymorphism (SSCP) analysis of the
      amplified DNA. Direct sequencing was performed on gene fragments that showed
      altered mobility in SSCP analysis. RESULTS: Mutations in the p53 gene were
      detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors
      from non-carriers (two-sided P = .007). The p53 mutations were distributed
      throughout exons 4 through 10 and included both protein-truncating and missense
      mutations in both groups. CONCLUSIONS: A statistically significantly higher
      frequency of p53 mutations was found in breast tumors from carriers of BRCA1
      mutations than from noncarriers, which adds to the accumulating evidence that
      loss of p53 function is an important step in the molecular pathogenesis of BRCA1
      mutation-associated breast tumors. This finding may have implications for
      understanding phenotypic differences and potential prognostic differences between
      BRCA1 mutation-associated hereditary breast cancers and sporadic cancers.

PMID- 10070949
TI  - Re: Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on
      endometrial cancer growth.

PMID- 10070950
TI  - Re: Therapeutic targeting of transcription in acute promyelocytic leukemia by use
      of an inhibitor of histone deacetylase.

PMID- 10070951
TI  - Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.
AB  - A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in
      gastrointestinal cancer. The purpose of this study was to determine whether COX-2
      was expressed in adenocarcinoma of the human pancreas. Quantitative reverse
      transcription-PCR, immunoblotting, and immunohistochemistry were used to assess
      the expression of COX-2 in pancreatic tissue. Levels of COX-2 mRNA were increased
      by >60-fold in pancreatic cancer compared to adjacent nontumorous tissue. COX-2
      protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was
      undetectable in nontumorous pancreatic tissue. Immunohistochemical analysis
      showed that COX-2 was expressed in malignant epithelial cells. In cultured human
      pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by
      treatment with tumor-promoting phorbol esters. Taken together, these results
      suggest that COX-2 may be a target for the prevention or treatment of pancreatic
      cancer.

PMID- 10070952
TI  - Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the
      head and neck.
AB  - The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was
      overexpressed in squamous cell carcinoma of the head and neck (HNSCC).
      Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry
      were used to assess the expression of COX-2 in head and neck tissue. Mean levels
      of COX-2 mRNA were increased by nearly 150-fold in HNSCC (n = 24) compared with
      normal oral mucosa from healthy volunteers (n = 17). Additionally, there was
      about a 50-fold increase in amounts of COX-2 mRNA in normal-appearing epithelium
      adjacent to HNSCC (n = 10) compared with normal oral mucosa from healthy
      volunteers. Immunoblotting demonstrated that COX-2 protein was present in six of
      six cases of HNSCC but was undetectable in normal oral mucosa from healthy
      subjects. Immunohistochemical analysis showed that COX-2 was expressed in both
      HNSCC and adjacent normal-appearing epithelium. Taken together, these results
      suggest that COX-2 may be a target for the prevention or treatment of HNSCC.

PMID- 10070953
TI  - High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer
      patients without family history.
AB  - To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of
      male breast cancer in Hungary, the country with the highest male breast cancer
      mortality rates in continental Europe, a series of 18 male breast cancer patients
      and three patients with gynecomastia was analyzed for germ-line mutations in both
      BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18
      male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene.
      Unexpectedly, none of them reported a family history for breast/ovarian cancer.
      Four of six truncating mutations were novel, and two mutations were recurrent.
      Four patients (22%) had a family history of breast/ovarian cancer in at least one
      first- or second-degree relative; however, no BRCA2 mutation was identified among
      them. No mutation was identified in either of the genes in the gynecomastias.
      These results provide evidence for a strong genetic component of male breast
      cancer in Hungary.

PMID- 10070954
TI  - Identification of an endogenous dominant-negative short isoform of caspase-9 that
      can regulate apoptosis.
AB  - Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x,
      Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis.
      Here, we describe the identification of an endogenous alternatively spliced
      isoform of caspase-9, named caspase-9b, which lacks the central large subunit
      caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the
      mRNA and protein levels. Caspase-9b can interact with the caspase recruitment
      domain of Apaf-1, and like the active site mutant of caspase-9, it can inhibit
      multiple forms of apoptosis, including those triggered by oligomerization of
      death receptors. It can also block activation of caspase-9 and -3 by Apaf-1 in an
      in vitro cytochrome c-dependent caspase activation assay. These results suggest
      that caspase-9b functions as an endogenous apoptosis inhibitory molecule by
      interfering with the formation of a functional Apaf-1-caspase-9 complex.

PMID- 10070955
TI  - Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1,
      MUC2, MUC5AC, and MUC6) expression.
AB  - Intestinal metaplasia is a well-established premalignant condition of the stomach
      that is characterized by mucin carbohydrate modifications defined by
      histochemical methods. The purpose of the present study was to see whether the
      expression of mucin core proteins was modified in the different types of
      intestinal metaplasia and to evaluate the putative usefulness of mucins as
      "molecular markers" in this setting. We used a panel of monoclonal antibodies
      with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize
      the expression pattern of mucins. In contrast to normal gastric mucosa, the
      complete form or type I intestinal metaplasia (n = 20) displayed little or no
      expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong
      expression of the intestinal mucin MUC2 in the goblet cells of all cases. The
      incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n =
      16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar
      cells. MUC6 was also expressed in 16 cases of type II intestinal metaplasia and
      in 11 cases of type III intestinal metaplasia. The intestinal mucin MUC2 was
      expressed in every case of incomplete intestinal metaplasia, mostly in goblet
      cells. The mucin expression profile in the different types of intestinal
      metaplasia allows the identification of two patterns: one defined by decreased
      levels of expression of "gastric" mucins (MUC1, MUC5AC, and MUC6) and expression
      of MUC2 intestinal mucin, which corresponds to type I intestinal metaplasia, and
      the other defined by coexpression of "gastric mucins" (MUC1, MUC5AC, and MUC6)
      together with the MUC2 mucin, encompassing types II and III intestinal
      metaplasia. Our results challenge the classical sequential pathway of intestinal
      metaplasia (from type I to type III via a type II intermediate step).

PMID- 10070956
TI  - Loss of normal G1 checkpoint control is an early step in carcinogenesis,
      independent of p53 status.
AB  - Recent studies have described a diminished radiation-induced G1 arrest in some
      wild-type (wt) p53 human tumor cell lines compared to normal human fibroblasts.
      However, the significance of this finding was unclear, particularly because tumor
      cell lines may have accumulated additional genetic changes after long periods in
      culture. Because malignant transformation of individual cells is thought to be an
      early step in carcinogenesis, we have used a model system of normal and
      transformed mouse fibroblast 10T1/2 cell clones to examine whether loss of G1
      checkpoint control may be an early event in tumor development and to study the
      relationships between G1 arrest, radiosensitivity, and genetic alterations.
      Twelve transformed clones were established from type III foci induced by
      irradiation of normal 10T1/2 cells and were compared with six clones derived from
      wt 10T1/2 cells. Three of the transformed clones expressed mutant p53; two of
      these had the same point mutation at codon 132 (exon 5), and one had a point
      mutation at codon 135. The remaining transformed and normal clones had wt p53
      status. The radiosensitivity of transformed clones, as measured by a clonogenic
      assay, was similar to that of normal clones; the three clones with mutant p53 did
      not differ from the others. There was no relationship between G1 arrest and
      radiosensitivity. Normal 10T1/2 cell clones showed a transient G1 arrest lasting
      approximately 9 h after 6 Gy of irradiation. This G1 arrest was either absent or
      markedly reduced in all of the transformed clones, regardless of p53 status.
      These results suggest that diminished G1 checkpoint control is an early event in
      the process of carcinogenesis that is associated with the malignant
      transformation of individual cells and is independent of p53 status.

PMID- 10070957
TI  - The relationship between a polymorphism in CYP17 with plasma hormone levels and
      breast cancer.
AB  - The A2 allele of CYP17 has been associated with polycystic ovarian syndrome,
      elevated levels of certain steroid hormones in premenopausal women, and increased
      breast cancer risk. We prospectively assessed the association between the A2
      allele of CYP17 and breast cancer risk in a case-control study nested within the
      Nurses' Health Study cohort. We also evaluated associations between this CYP17
      genotype and plasma steroid hormone levels among postmenopausal controls not
      using hormone replacement to assess the biological significance of this genetic
      variant. Women with the A2 allele were not at an increased risk of incident
      breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or
      advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence
      that the inverse association of late age at menarche with breast cancer may be
      modified by the CYP17 A2 allele. The protective effect of later age at menarche
      was only observed among women without the A2 allele (A1/A1 genotype: for age at
      menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2
      genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among
      controls, we found women with the A2/A2 genotype to have elevated levels of
      estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P
      = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P =
      0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women
      with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies
      endogenous hormone levels, but is not a strong independent risk factor for breast
      cancer.

PMID- 10070958
TI  - Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226
      myeloma cell line.
AB  - Selection for in vitro drug resistance can result in a complex phenotype with
      more than one mechanism of resistance emerging concurrently or sequentially. We
      examined emerging mechanisms of drug resistance during selection with
      mitoxantrone in the human myeloma cell line 8226. A novel transport mechanism
      appeared early in the selection process that was associated with a 10-fold
      resistance to mitoxantrone in the 8226/MR4 cell line. The reduction in
      intracellular drug concentration was ATP-dependent and ouabain-insensitive. The
      8226/MR4 cell line was 34-fold cross-resistant to the fluorescent aza
      anthrapyrazole BBR 3390. The resistance to BBR 3390 coincided with a 50%
      reduction in intracellular drug concentration. Confocal microscopy using BBR 3390
      revealed a 64% decrease in the nuclear:cytoplasmic ratio in the drug-resistant
      cell line. The reduction in intracellular drug concentration of both mitoxantrone
      and BBR 3390 was reversed by a novel chemosensitizing agent, fumitremorgin C. In
      contrast, fumitremorgin C had no effect on resistance to mitoxantrone or BBR 3390
      in the P-glycoprotein-positive 8226/DOX6 cell line. Increasing the degree of
      resistance to mitoxantrone in the 8226 cell line from 10 to 37 times (8226/MR20)
      did not further reduce the intracellular drug concentration. However, the
      8226/MR20 cell line exhibited 88 and 70% reductions in topoisomerase II beta and
      alpha expression, respectively, compared with the parental drug sensitive cell
      line. This decrease in topoisomerase expression and activity was not observed in
      the low-level drug-resistant, 8226/MR4 cell line. These data demonstrate that low
      level mitoxantrone resistance is due to the presence of a novel, energy-dependent
      drug efflux pump similar to P-glycoprotein and multidrug resistance-associated
      protein. Reversal of resistance by blocking drug efflux with fumitremorgin C
      should allow for functional analysis of this novel transporter in cancer cell
      lines or clinical tumor samples. Increased resistance to mitoxantrone may result
      from reduced intracellular drug accumulation, altered nuclear/cytoplasmic drug
      distribution, and alterations in topoisomerase II activity.

PMID- 10070959
TI  - Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells
      that display short-term interleukin 1alpha expression.
AB  - Expression of cytokines in malignant cells represents a novel approach for
      therapeutic treatment of tumors. Previously, we demonstrated the
      immunostimulatory effectiveness of interleukin 1alpha (IL-1alpha) gene transfer
      in experimental fibrosarcoma tumors. Here, we report the antitumor and
      immunotherapeutic effects of short-term expression of IL-1alpha by malignant T
      lymphoma cells. Activation in culture of T lymphoma cells with lipopolysaccharide
      stimulated macrophages induces the expression of IL-1alpha. The short-term
      expression of IL-1alpha persists in the malignant T cells for a few days
      (approximately 3-6 days) after termination of the in vitro activation procedure
      and, thus, has the potential to stimulate antitumor immune responses in vivo. As
      an experimental tumor model, we used the RO1 invasive T lymphoma cell line. Upon
      i.v. inoculation, these cells invade the vertebral column and compress the spinal
      cord, resulting in hind leg paralysis and death of the mice. Activated RO1 cells,
      induced to express IL-1alpha in a short-term manner, manifested reduced
      tumorigenicity: approximately 75% of the mice injected with activated RO1 cells
      remained tumor free. IL-1 was shown to be essential for the eradication of
      activated T lymphoma cells because injection of activated RO1 cells together with
      IL-1-specific inhibitors, i.e., the IL-1 receptor antagonist or the M 20 IL-1
      inhibitor, reversed reduced tumorigenicity patterns and led to progressive tumor
      growth and death of the mice. Furthermore, activated RO1 cells could serve as a
      treatment by intervening in the growth of violent RO1 cells after tumor take.
      Thus, when activated RO1 cells were injected 6 or 9 days after the inoculation of
      violent cells, mortality was significantly reduced. IL-1alpha, in its unique
      membrane-associated form, in addition to its cytosolic and secreted forms, may
      represent a focused adjuvant for potentiating antitumor immune responses at low
      levels of expression, below those that are toxic to the host. Further assessment
      of the immunotherapeutic potential of short-term expression of IL-1alpha in
      activated tumor cells may allow its improved application in the treatment of
      malignancies.

PMID- 10070960
TI  - A novel taxane with improved tolerability and therapeutic activity in a panel of
      human tumor xenografts.
AB  - Clinically available taxanes represent one of the most promising class of
      antitumor agents, despite several problems with their solubility and toxicity. In
      an attempt to improve the pharmacological profile of taxanes, a new series of
      analogues was synthesized from 14beta-hydroxy-10-deacetylbaccatin III and tested
      in a panel of human tumor cell lines. On the basis of the pattern of cytotoxicity
      and lack of cross-resistance in tumor cell lines expressing the typical multidrug
      resistant phenotype, a compound (IDN5109) was selected for preclinical
      development. A comparative efficacy study of IDN5109 and paclitaxel was performed
      using a large panel of human tumor xenografts, characterized by intrinsic (seven
      tumors) or acquired (four tumors) resistance to cisplatin or doxorubicin,
      including four ovarian, one breast, one cervical, three lung, one colon, and one
      prostatic carcinoma. Drugs were delivered i.v. according to the same schedule
      (four times every 4th day). IDN5109 achieved a very high level of activity
      (percentage tumor weight inhibition >70%; log10 cell kill >1) in all but one of
      the tested tumors. Compared to paclitaxel, IDN5109 exhibited a significantly
      superior activity in six tumors (including the four tumors that were resistant to
      paclitaxel) and a comparable activity against the other five paclitaxel
      responsive tumors. Additional advantages of IDN5109 over paclitaxel were also
      suggested by its toxicity profile. IDN5109 was not only less toxic (maximal
      tolerated doses were 90 and 54 mg/kg for IDN5109 and paclitaxel, respectively),
      but it also appeared to be endowed with a reduced neurotoxic potential and an
      improved profile of tolerability compared to the parent drug. Furthermore, the
      best antitumor efficacy was often already reached with doses lower than the
      maximal tolerated dose, suggesting an improved therapeutic index for the new
      drug. In conclusion, the results support the preclinical interest of IDN5109 in
      terms of the toxicity profile and of the efficacy with particular reference to
      the ability to overcome multiple mechanisms of drug resistance.

PMID- 10070961
TI  - Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in
      plasma cells from myeloma patients.
AB  - Recent data have renewed the interest for arsenic-containing compounds as
      anticancer agents. In particular, arsenic trioxide (As2O3) has been demonstrated
      to be an effective drug in the treatment of acute promyelocytic leukemia by
      inducing programmed cell death in leukemic cells both in vitro and in vivo. This
      prompted us to study the in vitro effects of As2O3 and of another arsenical
      derivative, the organic compound melarsoprol, on human myeloma cells and on the
      plasma cell differentiation of normal B cells. At pharmacological concentrations
      (10(-8) to 10(-6) mol/L), As2O3 and melarsoprol caused a dose- and time-dependent
      inhibition of survival and growth in myeloma cell lines that was, in some,
      similar to that of acute promyelocytic leukemia cells. Both arsenical compounds
      induced plasma cell apoptosis, as assessed by 4',6-diamidino-2-phenylindole
      staining, detection of phosphatidylserine at the cell surface using annexin V,
      and by the terminal deoxynucleotidyl transferase-mediated nick end labeling
      assay. As2O3 and melarsoprol also inhibited viability and growth and induced
      apoptosis in plasma-cell enriched preparations from the bone marrow or blood of
      myeloma patients. In nonseparated bone marrow samples, both arsenical compounds
      triggered death in myeloma cells while sparing most myeloid cells, as
      demonstrated by double staining with annexin V and CD38 or CD15 antibodies. In
      primary myeloma cells as in cell lines, interleukin 6 did not prevent arsenic
      induced cell death or growth inhibition, and no synergistic effect was observed
      with IFN-alpha. In contrast to As2O3, melarsoprol only slightly reduced the
      plasma cell differentiation of normal B cells induced by pokeweed mitogen. Both
      pokeweed mitogen-induced normal plasma cells and malignant plasma cells showed a
      normal nuclear distribution of PML protein, which was disrupted by As2O3 but not
      by melarsoprol, suggesting that the two arsenical derivatives acted by different
      mechanisms. These results point to the use of arsenical derivatives as
      investigational drugs in the treatment of multiple myeloma.

PMID- 10070962
TI  - Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with
      irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model.
AB  - 6-Hydroxymethylacylfulvene (MGI-114) is a semisynthetic analogue of the toxin
      illudin S, a product of the Omphalotus mushroom. MGI-114 induces cytotoxicity in
      a variety of solid tumors in vivo, including the refractory HT29 human colon
      cancer xenograft. In this study, the potential application of MGI-114 in the
      treatment of colon cancer was further explored by evaluating the activity of MGI
      114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU). Groups of 9
      nude mice bearing HT29 xenografts were treated with either single agent MGI-114,
      CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU. MGI-114 was
      administered at doses of 3.5 and 7 mg/kg i.p. daily on days 1 through 5, and CPT
      11 and 5FU were administered at doses of 50 and 100 mg/kg i.p. on days 1, 12, and
      19. In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in
      decreased final tumor weights compared with vehicle-treated controls (P<0.05),
      but only MGI-114 at 7 mg/kg produced partial responses. When MGI-114 at 3.5 mg/kg
      was combined with CPT-11, significant decrements in final tumor weights occurred
      compared with monotherapy with the same doses of MGI-114 and CPT-11 (P< or
      =0.001). Also, administration of the low-dose combination (MGI-114 at 35 mg/kg
      and CPT-11 at 50 mg/kg) resulted in final tumor weights similar to those achieved
      after administration of high-dose MGI-114 as a single agent. Moreover, the
      combination of MGI-114 and CPT-11 produced partial responses in nearly all of the
      animals, with some animals achieving complete responses. The outcome with the
      combination of MGI-114 and 5FU was less striking, with fewer partial responses
      and no complete responses. These results suggest enhanced activity when MGI-114
      is combined with CPT-11, and clinical trials to further evaluate this combination
      regimen are planned.

PMID- 10070963
TI  - Altered pharmacokinetics of a novel anticancer drug, UCN-01, caused by specific
      high affinity binding to alpha1-acid glycoprotein in humans.
AB  - The large species difference in the pharmacokinetics/pharmacodynamics of 7
      hydroxystaurosporine (UCN-01) can be partially explained by the high affinity
      binding of UCN-01 to human alpha1-acid glycoprotein (AGP) (Fuse et al, Cancer
      Res., 58: 3248-3253, 1998). To confirm whether its binding to human AGP actually
      changes the in vivo pharmacokinetics, we have studied the alteration in its
      pharmacokinetics after simultaneous administration of human AGP to rats: (a) the
      protein binding of UCN-01 was evaluated by chasing its dissociation from proteins
      using dextran-coated charcoal. The UCN-01 remaining 0.1 h after adding dextran
      coated charcoal to human plasma or AGP was approximately 80%, although the values
      for other specimens, except monkey plasma (approximately 20%), were <1%,
      indicating that the dissociation from human AGP was specifically slower than from
      other proteins; and (b) the pharmacokinetics of UCN-01 simultaneously
      administered with human AGP has been determined. The plasma concentrations after
      i.v. administration of UCN-O1 with equimolar human AGP were much higher than
      those after administration of UCN-01 alone. The steady-state distribution volume
      and the systemic clearance were reduced to about 1/100 and 1/200, respectively.
      Human AGP thus reduced the distribution and elimination of UCN-01 substantially.
      On the other hand, dog AGP, which has a low binding affinity for UCN-01, did not
      change the pharmacokinetics of UCN-01 so much. Furthermore, human AGP markedly
      reduced the hepatic extraction ratio of UCN-01 from 0.510 to 0.0326. Also, human
      AGP (10 microM) completely inhibited the initial uptake of UCN-01 (1 microM) into
      isolated rat hepatocytes, whereas the uptake of UCN-01 was unchanged in the
      presence of human serum albumin (10 microM). In conclusion, the high degree of
      binding of UCN-01 to human AGP causes a reduction in the distribution and
      clearance, resulting in high plasma concentrations in humans.

PMID- 10070964
TI  - Human colon adenocarcinomas express a MUC1-associated novel carbohydrate epitope
      on core mucin glycans defined by a monoclonal antibody (A10) raised against
      murine Ehrlich tumor cells.
AB  - A monoclonal antibody (mAb; A10) raised against murine Ehrlich tumor cell surface
      carbohydrates was tested for reactivity with human normal and malignant tissues.
      A10 reacted strongly, with a high proportion of adenocarcinomas arising from
      colon and other tissues but not with breast carcinomas or other malignant tumors.
      Normal tissues were virtually A10 unreactive, except for the duct cells from
      breast and pancreas and some bronchial mucosae. Ultrastructural studies showed
      mAb A10 immunolabeling of both microvilli and mucin droplets in colon cancer
      cells but not in normal absorptive or globet cells. A10 reacted strongly with
      mucin-enriched fractions from colon cancer tissues and HT-29 xenografts but not
      from normal colon tissues. A10 epitope was carried on MUC1 derived from colon
      adenocarcinomas and probably on other mucin species, although not on MUC2
      molecules. A10 epitope was resistant to exoglycosidases and periodate oxidation
      but sensitive to the Smith's degradation and beta-elimination, suggesting the
      involvement of O-linked carbohydrates in nonterminal reducing positions. A mucin
      type glycosidic linkage was supported because of the lack of A10 reactivity with
      HT-29 cells grown with phenyl-N-acetyl-alpha-D-galactosaminide. Deglycosylation
      studies with trifluoromethanesulfonic acid pointed to the involvement of core
      mucin glycans in the A10 epitope. This epitope was resistant to protease, O- and
      N-glycanase treatments carried out on trifluoromethanesulfonic acid
      deglycosylated mucins. Inhibition studies with core 1, core 2, core 3, and core 6
      suggested the latter [GlcNAcbeta(1-6)GalNAc] as being involved in A10 epitope.
      Taken together, the present results point to A10 defining a core 6-related
      epitope on core mucin glycans expressed by colon cancer MUC1 not previously
      associated with human cancer.

PMID- 10070965
TI  - T-cell receptor transgenic analysis of tumor-specific CD8 and CD4 responses in
      the eradication of solid tumors.
AB  - The role of tumor-specific CD8 and CD4 lymphocytes in rejecting solid tumors has
      been difficult to determine because of the lack of models in which tumor antigen,
      specific CD8 cells, and specific CD4 cells can be monitored and controlled. To
      investigate the minimal components required for the induction and maintenance of
      CTL activity sufficient to reject a solid tumor in vivo, we transfected the
      influenza hemagglutinin (HA) gene into a nonimmunogenic class I+/class II- murine
      malignant mesothelioma (MM) tumor line to generate an endogenous tumor antigen
      and used TCR transgenic mice with class I- or class II-restricted specificities
      for HA as sources of naive, tumor-specific T cells. The data show that the
      presence of a strong tumor antigen is not in itself sufficient to induce an
      effective CTL response, nor does the presence of a high frequency of precursor
      cells guarantee tumor rejection. We also show that tumor-specific CD4 cells, when
      CTL numbers are suboptimal, greatly enhance the eradication of tumor, confirming
      the importance of antigen-presenting cell presentation of tumor antigens to class
      II-restricted cells. These data confirm that T-cell receptor transgenic cells,
      combined with nominal tumor antigen transfection, represent powerful tools to
      analyze tumor-specific T-cell responses.

PMID- 10070966
TI  - Evidence for involvement of B lymphocytes in the surveillance of lung metastasis
      in the rat.
AB  - These studies examined the composition of lymphocytes within the lung after the
      introduction of tumor cells that metastasize to the lung in rats. i.v. delivery
      of MADB106 tumor cells into syngeneic Fischer 344 rats caused dose- and time
      dependent development of lung tumors, with surface metastases evident 7 days
      after injection and markedly increased 11 days after injection. The total number
      of lymphocytes recovered from the lung was increased 11 days after injection but
      not 7 days after injection. When lymphocytes from the lung, spleen, and blood
      were subjected to fluorescence-activated cell sorting analysis, the most
      conspicuous change was an increase in the percentage of CD45RA+ cells (i.e., B
      lymphocytes in the rat) in the lung, with no changes seen in the percentage of
      natural killer (NKR-P1+), CD4+, or CD8+ cells in the lung. Analysis of the time
      course showed that B lymphocytes increased in the lung soon after i.v. tumor
      injection, with an initial peak seen 6 h after injection. Rapid influx of B
      lymphocytes into lung after i.v. tumor cell injection was also observed in
      another syngeneic tumor model, i.e., after injection of CC531 cells into WAG
      rats. To determine whether the influx of B lymphocytes into the lung might
      participate in tumor surveillance, a high dose of antibody (100 microg) to rat B
      lymphocytes was given to immunoneutralize these cells; this produced an increase
      in lung tumors in both models. Finally, Fischer 344 rats were given a s.c.
      injection of MADB106 tumor cells that made them resistant to lung tumors when
      given a later i.v. injection of these tumor cells. These animals were found to
      have an elevated level of B lymphocytes residing in the lung associated with the
      resistance to lung tumor. These findings suggest that early responses of B
      lymphocytes are important in protection against tumor development in two rat
      models of cancer.

PMID- 10070967
TI  - Hypermethylation of the hMLH1 gene promoter in human gastric cancers with
      microsatellite instability.
AB  - Human gastric carcinoma shows a higher prevalence of microsatellite instability
      (MSI) than does any other type of sporadic human cancer. The reasons for this
      high frequency of MSI are not yet known. In contrast to endometrial and
      colorectal carcinoma, mutations of the DNA mismatch repair (MMR) genes hMLH1 or
      hMSH2 have not been described in gastric carcinoma. However, hypermethylation of
      the hMLH1 MMR gene promoter is quite common in MSI-positive endometrial and
      colorectal cancers. This hypermethylation has been associated with hMLH1
      transcriptional blockade, which is reversible with demethylation, suggesting that
      an epigenetic mechanism underlies hMLH1 gene inactivation and MMR deficiency.
      Therefore, we studied the prevalence of hMLH1 promoter hypermethylation in a
      total of 65 gastric tumors: 18 with frequent MSI (MSI-H), 8 with infrequent MSI
      (MSI-L), and 39 that were MSI negative. We found a striking association between
      hMLH1 promoter hypermethylation and MSI; of 18 MSI-H tumors, 14 (77.8%) showed
      hypermethylation, whereas 6 of 8 MSI-L tumors (75%) were hypermethylated at
      hMLH1. In contrast, only 1 of 39 (2.6%) MSI-negative tumors demonstrated hMLH1
      hypermethylation (P<0.0001 for MSI-H or MSI-L versus MSI-negative). Moreover,
      hypermethylated cancers demonstrated diminished expression of hMLH1 protein by
      both immunohistochemistry and Western blotting, whereas nonhypermethylated tumors
      expressed abundant hMLH1 protein. These data indicate that hypermethylation of
      hMLH1 is strongly associated with MSI in gastric cancers and suggest an
      epigenetic mechanism by which defective MMR occurs in this group of cancers.

PMID- 10070968
TI  - G-protein gamma 7 is down-regulated in cancers and associated with p 27kip1
      induced growth arrest.
AB  - We previously identified and cloned human G protein gamma 7 (G-gamma 7) gene,
      which is down-regulated in pancreatic cancer. We examined G-gamma 7 expression in
      other gastrointestinal tract cancers. In 24 of 30 patients with gastrointestinal
      tract cancer, Northern blot assay and immunohistochemical staining revealed
      significantly lower G-gamma 7 expression in tumors than in normal tissues from
      the same patients. Semiquantitative reverse transcription PCRs also showed lower
      G-gamma 7 expression in tumors than in corresponding normal tissues in 69 of 90
      patients. To examine the biological role of G-gamma 7 in cancer, the G-gamma 7
      cDNA was transfected into a human esophageal carcinoma cell line, KYSE150, that
      lacks G-gamma 7 expression. G-gamma 7 expression suppressed cell growth and
      tritiated-thymidine uptake when cells were confluent G-gamma 7 expression also
      suppressed tumorigenicity in BALB/c nude mice until 3 weeks after
      transplantation. G-gamma 7 expression increased the Go/G1 population and
      decreased the S phase population when cells were at high density. We confirmed
      that this change was associated with p27K1P1 expression. These findings suggest
      that human G-gamma 7 is associated with p27kip1-induced growth arrest and may be
      a therapeutic target in cancers.

PMID- 10070969
TI  - Increased ultraviolet sensitivity and chromosomal instability related to P53
      function in the xeroderma pigmentosum variant.
AB  - The xeroderma pigmentosum (XP) variant (XPV) is a form of XP that has normal
      excision repair but shows defective DNA replication after UV irradiation. In
      developing various transformed fibroblast cell lines from these patients, we have
      found that there are significant phenotypic changes in transformed cells that
      seem to correlate with inactivation of p53. After transformation with SV40, XPV
      cell lines are only slightly UV sensitive, like their primary counterparts, but
      their sensitization with caffeine and the induction of sister chromatid exchanges
      (SCEs) by UV irradiation are greatly enhanced. After transformation by HPV16 E7,
      which targets the retinoblastoma cell cycle regulatory gene, there is no change
      in the UV sensitivity of XPV cells; but, when transformed by HPV16 E6 or E6 and
      E7 combined, there is a large increase in UV sensitivity and in the induction of
      SCEs. These changes are not associated with any detectable changes in the
      reactivation of an externally irradiated luciferase expression vector, the
      excision of cyclobutane pyrimidine dimers from bulk DNA, or unscheduled DNA
      synthesis and, therefore, do not involve excision repair. We suggest that if SCEs
      represent homologous recombination between sister chromatids, then in the absence
      of p53 function, the DNA chain arrest typical of UV-damaged XPV cells initiates
      strand exchange during recovery. In untransformed cells with normal p53, the
      preferred mode of recovery would then be replication bypass. The symptoms of
      elevated solar carcinogenesis in XPV patients may, therefore, be associated with
      increased genomic instability in cells of the skin in which p53 is inactivated by
      UV-induced mutations.

PMID- 10070970
TI  - Ethylnitrosourea-induced development of malignant schwannomas in the rat: two
      distinct loci on chromosome of 10 involved in tumor susceptibility and
      oncogenesis.
AB  - Inbred rodent strains with differing sensitivity to experimental tumor induction
      provide model systems for the detection of genes that either are responsible for
      cancer predisposition or modify the process of carcinogenesis. Rats of the inbred
      BD strains differ in their susceptibility to the induction of neural tumors by N
      ethyl-N-nitrosourea (EtNU). Newborn BDIX rats that are exposed to EtNU (80
      microg/g body weight; injected s.c.) develop malignant schwannomas predominantly
      of the trigeminal nerves with an incidence >85%, whereas BDIV rats are entirely
      resistant. A T:A-->A:T transversion mutation at nucleotide 2012 of the neu (erbB
      2) gene on chromosome 10, presumably the initial event in EtNU-induced schwannoma
      development, is later followed by loss of the wild-type neu allele. Genetic
      crosses between BDIX and BDIV rats served: (a) to investigate the inheritance of
      susceptibility; (b) to obtain animals informative for the mapping of losses of
      heterozygosity (LOH) in tumors with polymorphic simple sequence length
      polymorphisms (SSLPs); and (c) to localize genes associated with schwannoma
      susceptibility by linkage analysis with SSLPs. Schwannoma development was
      strongly suppressed in F1 animals (20% incidence). All of the F1 schwannomas
      displayed LOH on chromosome 10, with a consensus region on the telomeric tip
      encompassing D10Rat3, D10Mgh16 and D10Rat2 but excluding neu. A strong bias
      toward losing the BDIV alleles suggests the involvement of a BDIV-specific tumor
      suppressor gene(s). Targeted linkage analysis with chromosome 10 SSLPs in F2
      intercross and backcross animals localized schwannoma susceptibility to a region
      around D10Wox23, 30 cM centromeric to the tip. Ninety-four % of F1 tumors
      exhibited additional LOH at this region. Two distinct loci on chromosome 10 may
      thus be connected with susceptibility to the induction and development of
      schwannomas in rats exposed to EtNU.

PMID- 10070971
TI  - Use of a novel fibronectin receptor for liver infiltration by a mouse lymphoma
      cell line RL-male1.
AB  - The mechanism whereby some lymphomas invade liver extensively has not been fully
      investigated. There is no basement membrane under the sinusoidal endothelium of
      the liver, and hepatocytes produce fibronectin (FN); therefore, adhesion to this
      FN may be particularly important for liver infiltration by lymphoma cells. A
      mouse lymphoma cell line, RL-male1, adhered to FN. However, this cell line did
      not express classical FN receptors such as very late antigen (VLA)-4 and VLA-5,
      as estimated by immunofluorescent staining. We have generated monoclonal
      antibodies (mAbs) that inhibit adhesion of RL-male1 cells to FN. Western blot and
      immunoprecipitation analyses showed that the new mAbs recognize a protein with an
      approximate molecular weight of 55,000 (p55). This antigenic protein was highly
      purified by immunoprecipitation and processed for microsequencing. From NH2
      terminal sequence results, the p55 antigen was not identical to known FN
      receptors. Radioisotope-labeled RL-male1 cells, when injected i.v. into mice,
      rapidly infiltrated the liver (30-35% of injected cells), as measured by a gamma
      counter. Intravenous injection of the new mAbs partially (20%) blocked the
      infiltration of i.v.-injected lymphoma cells into the liver, whereas control rat
      IgG and an anti-CD11a mAb did not. These results demonstrate that the mouse
      lymphoma cell line RL-male1 nses a novel FN receptor for liver infiltration.

PMID- 10070972
TI  - Ret-mediated mitogenesis requires Src kinase activity.
AB  - The proto-oncogene RET encodes a transmembrane growth neurotrophic receptor with
      tyrosine kinase (TK) activity. RET mutations are associated with several human
      neoplastic and nonneoplastic diseases, including thyroid papillary carcinoma,
      multiple endocrine neoplasia type 2 syndromes, and Hirschsprung's disease.
      Activation of receptor TKs results in the binding and activation of downstream
      signaling proteins, among which are nonreceptor TKs of the Src family. To test
      the involvement of c-Src in Ret-mediated signaling, we measured the levels of c
      Src activity in NIH3T3 cells coexpressing Ret and the accessory GFR alpha-1
      receptor or an epidermal growth factor receptor/Ret chimeric receptor when the
      cells were stimulated by glial cell line-derived neurotrophic factor or epidermal
      growth factor, respectively. Ret stimulation resulted in the activation of c-Src.
      We also measured the levels of Src kinase activity in cell lines expressing
      isoforms of the Ret receptor activated by different mutations. These cells showed
      higher Src kinase activity than the normal counterpart. Furthermore, we show that
      Ret is able to associate with the SH2 domain of Src in a phosphotyrosine
      dependent fashion. Microinjection of a kinase inactive mutant of c-Src blocked
      Ret-mediated mitogenic effect. These experiments demonstrate that activated Ret
      is able to bind and stimulate c-Src kinase and that Src activation is essential
      for the mitogenic activity of Ret.

PMID- 10070973
TI  - Nonpolarized secretion of human meprin alpha in colorectal cancer generates an
      increased proteolytic potential in the stroma.
AB  - Epithelial cells of the normal human colonic mucosa secrete an astacin-type
      metalloprotease, meprin a (E. C. 3.4.24.18, N-benzoyl-L-tyrosyl-p-aminobenzoic
      acid hydrolase), into the intestinal lumen. We found that Caco-2 cells, a colon
      carcinoma cell line, expressed endogenous meprin alpha, which was secreted at
      both the basolateral and apical plasma membrane. The expression of meprin alpha
      in colorectal cancer was confirmed using Northern blot analysis. On tissue
      sections, a diversity of carcinoma cells with varying immunoreactivity for meprin
      alpha was observed. Western blots of a series of 11 paired samples of carcinomas
      and normal control colon tissue revealed that meprin alpha protein accumulated at
      significant levels in 6 carcinomas at Union International Contre le Cancer tumor
      stages I-IV. In contrast, the protease was never detected in normal control
      tissue samples. Meprin alpha zymogen was activated in the tumor tissue, as shown
      by a 3-fold increase in enzymatic activity. In conclusion, we describe a cancer
      specific sorting of meprin alpha, leading to a redistribution with consecutively
      increased proteolytic activity in the tumor stroma. Because the protease is known
      to cleave extracellular matrix components in vitro, meprin a may contribute to
      tumor progression by facilitating migration, intravasation, and metastasis of
      carcinoma cells.

PMID- 10070974
TI  - Cyclin D1 overexpression enhances radiation-induced apoptosis and
      radiosensitivity in a breast tumor cell line.
AB  - Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many
      different tumor types, such as breast carcinoma and squamous cell carcinoma of
      the head and neck. The overexpression of this protein is, in several cases,
      associated with a poor prognosis. In this study, the effect of cyclin D1 on
      radiosensitivity was investigated in a breast tumor cell line, MCF7, containing a
      cyclin D1 gene construct under the control of a tetracycline-sensitive regulator.
      MCF7 cells cultured without tetracycline resulted in a 6-fold increase in the
      cyclin D1 protein. Cyclin D1-overexpressing MCF7 cells were more sensitive to
      ionizing radiation than the nonoverexpressing counterparts. The cyclin D1
      overexpressing cells also exhibited a higher induction of apoptosis. Treatment
      with a dose of 5 Gy resulted in a rapid increase of p53 and p21 in the cyclin D1
      overexpressing cells. Nonoverexpressing cells showed a more transient expression
      of these proteins after ionizing radiation. A pronounced G2-M block was observed
      in both cell lines. The cyclin D1-overexpressing cells were, however, released
      earlier from the block than the control cells. These data suggest that
      overexpression of cyclin D1 alters sensitivity toward ionizing radiation by
      modulating gamma-radiation-induced G2-M transition.

PMID- 10070975
TI  - Overproduction of hyaluronan by expression of the hyaluronan synthase Has2
      enhances anchorage-independent growth and tumorigenicity.
AB  - Hyaluronan (HA) has long been implicated in malignant transformation and tumor
      progression. However, due to the lack of molecular tools to directly manipulate
      production of HA, which does not require a core protein for its synthesis, our
      understanding of the role of HA in tumor cells has been largely circumstantial.
      In this study, we genetically manipulated the production of HA by transfection of
      a mammalian HA synthase Has2 into human HT1080 cells and examined the malignant
      phenotype of transfected cells. We found that increased production of HA promotes
      anchorage-independent growth and tumorigenicity of the cells. Has2-transfected
      cells formed greater numbers of colonies in semisolid medium. Tumors in nude mice
      derived from Has2-transfected cells grew more rapidly and were 2-4 times larger
      than those derived from control cells at termination of experiments. Histological
      and biochemical analyses of tumors revealed no significant differences in cell
      density and tissue structures between them, indicating that the larger size of
      the tumors was due to enhanced cell proliferation, not to increased accumulation
      of tumor stroma or increased angiogenesis. These results demonstrate that HA
      production by tumor cells per se promotes proliferation of these cells in tissues
      and provides direct evidence for the role of HA in tumorigenicity.

PMID- 10070976
TI  - Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream
      response to androgen or growth factor stimulation of prostate cancer cells.
AB  - Protein kinase CK2, a messenger-independent serine/threonine kinase, has been
      implicated in cell growth. Androgenic stimulus in rat prostate modulates its
      association with nuclear matrix (NM) and chromatin. Because the growth of human
      prostate carcinoma cells is influenced by androgens and/or growth factors, we
      determined the nature of CK2 signaling in the NM in response to androgen and
      growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3
      cells were cultured in media to regulate their growth in the presence of 5alpha
      dihydrotestosterone (5alpha-DHT) or growth factors (epidermal growth factor,
      keratinocyte growth factor, and transforming growth factor alpha). The activity
      of CK2 was measured in the cytosolic and NM fractions isolated from these cells
      after treatment with growth stimuli. The changes in CK2 in various fractions were
      also confirmed by immunoblotting with a specific antibody. LNCaP cells responded
      to both 5alpha-DHT and growth factors for growth. The presence of these agents in
      the culture medium evoked a translocation of CK2 to the NM from the cytosol. The
      PC-3 cells did not respond to 5alpha-DHT for growth but did respond to growth
      factors. Under these conditions, there was also a translocation of CK2 to the NM
      concomitant with a decrease in the cytosolic fraction. These results suggest that
      CK2 translocation to the NM occurs in response to various growth stimuli in cells
      in culture. Thus, CK2 is a common downstream signal transducer in response to
      diverse growth stimuli that may relate to the pathobiology of prostate cancer
      cells.

PMID- 10070977
TI  - Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic
      transformation.
AB  - Bombesin-like peptides such as gastrin-releasing peptide (GRP) have been shown to
      play a role in cancer as autocrine growth factors that stimulate tumor growth
      through specific receptors. To search for potential clinical indications for GRP
      analogues, it is important to identify human tumor types expressing sufficient
      amounts of the respective receptors. In the present study, we have evaluated the
      expression of GRP receptors in human nonneoplastic and neoplastic prostate
      tissues using in vitro receptor autoradiography on tissue sections with 125I-Tyr4
      bombesin as radio-ligand. GRP receptors were detected, often in high density, in
      30 of 30 invasive prostatic carcinomas and also in 26 of 26 cases of prostatic
      intraepithelial proliferative lesions, corresponding mostly to prostatic
      intraepithelial neoplasias. Well-differentiated carcinomas had a higher receptor
      density than poorly differentiated ones. Bone metastases of androgen-independent
      prostate cancers were GRP receptor-positive in 4 of 7 cases. Conversely, GRP
      receptors were identified in only a few hyperplastic prostates and were localized
      in very low density in glandular tissue and, focally, in some stromal tissue. In
      all of the cases, the receptors corresponded to the GRP receptor subtype of
      bombesin receptors, having high affinity for GRP and bombesin and lower affinity
      for neuromedin B. These data demonstrate a massive GRP receptor overexpression in
      prostate tissues that are neoplastically transformed or, like prostatic
      intraepithelial neoplasias, are in the process of malignant transformation. GRP
      receptors may be markers for early molecular events in prostate carcinogenesis
      and useful in differentiating prostate hyperplasia from prostate neoplasia Such
      data may not only be of biological significance but may also provide a molecular
      basis for potential clinical applications such as GRP-receptor scintigraphy for
      early tumor diagnosis, radiotherapy with radiolabeled bombesin-like peptide
      analogues, and chemotherapy with cytotoxic bombesin analogues.

PMID- 10070978
TI  - A possible contributory role of BK virus infection in neuroblastoma development.
AB  - The tumor suppressor protein p53 is aberrantly localized to the cytoplasm of
      neuroblastoma cells, compromising the suppressor function of this protein. Such
      tumors are experimentally induced in transgenic mice expressing the large tumor
      (T) antigen of polyomaviruses. The oncogenic mechanisms of T antigen include
      complex formation with, and inactivation of, the tumor suppressor protein p53.
      Samples from 18 human neuroblastomas and five normal human adrenal glands were
      examined. BK virus DNA was detected in all neuroblastomas and none of five normal
      adrenal glands by PCR. Using DNA in situ hybridization, polyomaviral DNA was
      found in the tumor cells of 17 of 18 neuroblastomas, but in none of five adrenal
      medullas. Expression of the large T antigen was detected in the tumor cells of 16
      of 18 neuroblastomas, but in none of the five adrenal medullas. By double
      immunostaining BK virus T antigen and p53 was colocalized to the cytoplasm of the
      tumor cells. Immunoprecipitation revealed binding between the two proteins. The
      presence and expression of BK virus in neuroblastomas, but not in normal adrenal
      medulla, and colocalization and binding to p53, suggest that this virus may play
      a contributory role in the development of this neoplasm.

PMID- 10070979
TI  - 25 years of school-based health centers.

PMID- 10070980
TI  - Russian physicians helped to upgrade medical skills.

PMID- 10070981
TI  - Aging research on the international agenda.

PMID- 10070982
TI  - HELP network says firearms data gap makes reducing gun injuries more difficult.
      Handgun Epidemic Lowering Plan.

PMID- 10070983
TI  - From the Food and Drug Administration.

PMID- 10070984
TI  - From the Centers for Disease Control and Prevention. Bioterrorism alleging use of
      anthrax and interim guidelines for management--United States, 1998.

PMID- 10070985
TI  - From the Centers for Disease Control and Prevention. Surveillance of morbidity
      during wildfires--Central Florida, 1998.

PMID- 10070986
TI  - From the Centers for Disease Control and Prevention. Update: recommendations to
      prevent hepatitis B virus transmission--United States.

PMID- 10070987
TI  - Inhaled corticosteroids and likelihood of cataract extraction.

PMID- 10070988
TI  - Inhaled corticosteroids and likelihood of cataract extraction.

PMID- 10070989
TI  - Inhaled corticosteroids and likelihood of cataract extraction.

PMID- 10070990
TI  - Inhaled corticosteroids and likelihood of cataract extraction.

PMID- 10070991
TI  - Inhaled corticosteroids and likelihood of cataract extraction.

PMID- 10070992
TI  - Renin profiling to predict response to antihypertensive therapy.

PMID- 10070993
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070994
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070995
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070996
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070997
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070998
TI  - Hormone replacement therapy for secondary prevention of coronary heart disease.

PMID- 10070999
TI  - Sleep disorders and attention-deficit/hyperactivity disorder.

PMID- 10071000
TI  - Maternal psychological distress and parenting stress after the birth of a very
      low-birth-weight infant.
AB  - CONTEXT: Few studies document how parents adapt to the experience of a very low
      birth-weight (VLBW; <1500 g) birth despite societal concerns about the ethics and
      justification of intensive care for these infants. OBJECTIVE: To determine the
      degree and type of stress experienced over time by mothers whose infants vary in
      degree of prematurity and medical and developmental risk. DESIGN: Longitudinal
      prospective follow-up study of a cohort of mothers of high- and low-risk VLBW and
      term infants from birth to 3 years. SETTING: All level III neonatal intensive
      care units from a large midwestern metropolitan region. PARTICIPANTS: Mothers and
      infants prospectively and consecutively enrolled in a longitudinal study between
      1989 and 1991. High-risk VLBW infants were diagnosed as having bronchopulmonary
      dysplasia, and comparison groups were low-risk VLBW infants without
      bronchopulmonary dysplasia and term infants (>36 weeks, >2500 g). MAIN OUTCOME
      MEASURES: Standardized, normative self-report measures of maternal psychological
      distress, parenting stress, family impact, and life stressors. RESULTS: Mothers
      of VLBW infants (high risk, n = 122; low risk, n = 84) had more psychological
      distress than mothers of term infants (n=123) at 1 month (13% vs 1%; P = .003).
      At 2 years, mothers of low-risk VLBW infants did not differ from term mothers,
      while mothers of high-risk infants continued to report psychological distress. By
      3 years, mothers of high-risk VLBW children did not differ from mothers of term
      children in distress symptoms, while parenting stress remained greater. Severity
      of maternal depression was related to lower child developmental outcomes in both
      VLBW groups. CONCLUSIONS: The impact of VLBW birth varies with child medical risk
      status, age, and developmental outcome. Follow-up programs should incorporate
      psychological screening and support services for mothers of VLBW infants in the
      immediate postnatal period, with monitoring of mothers of high-risk VLBW infants.

PMID- 10071001
TI  - Incidence and clinical course of thrombotic thrombocytopenic purpura due to
      ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of
      Platelet IIb/IIIa Inhibitor for Stenting.
AB  - CONTEXT: Thrombotic thrombocytopenic purpura (TTP) is a rare and often fatal
      disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia,
      mental status changes, and renal dysfunction. Ticlopidine hydrochloride is 1 of
      several drugs that have been associated with this disorder and is currently used
      routinely in the approximately 500000 patients per year in the United States who
      undergo a percutaneous coronary intervention involving a stent. OBJECTIVES: To
      determine the incidence and describe the clinical course of TTP due to
      ticlopidine therapy following stenting. DESIGN: Retrospective analysis of cohort
      of all patients undergoing coronary stenting at the Evaluation of Platelet
      IIb/IIIa Inhibitor for Stenting (EPISTENT) study sites. SETTING: Sixty-three
      centers throughout the United States and Canada. PATIENTS: A total of 43322
      patients who underwent a percutaneous coronary intervention and received a
      coronary stent during a 1-year period from 1996 to 1997. MAIN OUTCOME MEASURES:
      Cases of TTP following stenting during the 1-year period to determine the
      incidence of TTP due to ticlopidine therapy following coronary stenting.
      Additional cases were collected from these and other centers across North America
      to further describe the clinical presentation and course of TTP due to
      ticlopidine therapy following stenting. RESULTS: Nine cases of TTP following
      stenting were recognized at the 63 centers during the specified period, giving an
      incidence of 1 case per 4814 patients treated (0.02%; 95% confidence interval, 1
      case per 2533 to 1 case per 10 541 patients treated). Ten additional cases of TTP
      related to ticlopidine therapy following stenting were identified from other
      centers, were identified from the primary centers outside the pre-defined period,
      or involved a noncoronary stent. Four patients (21%) received ticlopidine for 2
      weeks or fewer, 14 patients (74%) for 2 to 4 weeks, and 1 patient (5%) for 8
      weeks. The mean time of ticlopidine treatment prior to TTP diagnosis was 22 days
      (range, 5-60 days). The overall mortality rate was 21% (4/19), with all 4 deaths
      occurring in patients not treated with plasmapheresis, whereas there were no
      deaths among the 13 patients who received plasmapheresis. CONCLUSION: The
      findings of a TTP incidence of 0.02% in our cohort of ticlopidine-treated
      patients following coronary stenting suggests that TTP occurs much more commonly
      in this population than the estimated incidence of 0.0004% in the general
      population. The mortality rate for this rare complication exceeds 20%. Limiting
      ticlopidine therapy to 2 weeks after stenting does not prevent the development of
      TTP. Rapid diagnosis and treatment that includes plasmapheresis are critical for
      improved survival.

PMID- 10071002
TI  - Epidemiology, etiology, and impact of traveler's diarrhea in Jamaica.
AB  - CONTEXT: Traveler's diarrhea (TD) can incapacitate travelers. Characteristics of
      TD could be helpful in identifying individuals who might benefit from a vaccine
      against TD. OBJECTIVE: To determine epidemiology, etiology, and impact of TD in
      Jamaica. Design Two-armed, cross-sectional survey conducted between March 1996
      and May 1997. SETTING: Sangster International Airport and 10 hotels in Montego
      Bay area, Jamaica. SUBJECTS: To investigate epidemiology and impact, 30369 short
      term visitors completed a questionnaire just before boarding their homebound
      aircrafts. To investigate etiology, 322 patients (hotel guests) with TD provided
      stool samples. MAIN OUTCOME MEASURES: Attack and incidence rates of reported
      diarrhea and of classically defined TD (> or =3 unformed stool samples in 24
      hours and > or =1 accompanying symptom), incapacity, risk factors, and etiology.
      RESULTS: The attack rate for diarrhea was 23.6% overall, with 11.7% having
      classically defined TD. For a mean duration of stay of 4 to 7 days, the incidence
      rate was 20.9% (all TD) and 10.0% (classic TD). Among airport respondents, the
      incapacity lasted a mean of 11.6 hours. Less than 3% of all travelers avoided
      potentially high-risk food and beverages. The most frequently detected pathogens
      were enterotoxigenic Escherichia coli, Rotavirus, and Salmonella species.
      CONCLUSIONS: A realistic plan for reducing TD is needed. Preventive measures such
      as the improvement of hygienic conditions at the destination, and/or the
      development of vaccines against the most frequent pathogens associated with TD
      may contribute toward achieving this goal.

PMID- 10071003
TI  - Percutaneous electrical nerve stimulation for low back pain: a randomized
      crossover study.
AB  - CONTEXT: Low back pain (LBP) contributes to considerable disability and lost
      wages in the United States. Commonly used opioid and nonopioid analgesic drugs
      produce adverse effects and are of limited long-term benefit in the management of
      this patient population. OBJECTIVE: To compare the effectiveness of a novel
      nonpharmacologic pain therapy, percutaneous electrical nerve stimulation (PENS),
      with transcutaneous electrical nerve stimulation (TENS) and flexion-extension
      exercise therapies in patients with long-term LBP. DESIGN: A randomized, single
      blinded, sham-controlled, crossover study from March 1997 to December 1997.
      SETTING: An ambulatory pain management center at a university medical center.
      PATIENTS: Twenty-nine men and 31 women with LBP secondary to degenerative disk
      disease. INTERVENTIONS: Four therapeutic modalities (sham-PENS, PENS, TENS, and
      exercise therapies) were each administered for a period of 30 minutes 3 times a
      week for 3 weeks. MAIN OUTCOME MEASURES: Pretreatment and posttreatment visual
      analog scale (VAS) scores for pain, physical activity, and quality of sleep;
      daily analgesic medication usage; a global patient assessment questionnaire; and
      Health Status Survey Short Form (SF-36). RESULTS: PENS was significantly more
      effective in decreasing VAS pain scores after each treatment than sham-PENS,
      TENS, and exercise therapies (after-treatment mean +/- SD VAS for pain, 3.4+/-1.4
      cm, 5.5+/-1.9 cm, 5.6+/-1.9 cm, and 6.4+/-1.9 cm, respectively). The average +/-
      SD daily oral intake of nonopioid analgesics (2.6+/-1.4 pills per day) was
      decreased to 1.3+/-1.0 pills per day with PENS (P<.008) compared with 2.5+/-1.1,
      2.2+/-1.0, and 2.6+/-1.2 pills per day with sham-PENS, TENS, and exercise,
      respectively. Compared with the other 3 modalities, 91 % of the patients reported
      that PENS was the most effective in decreasing their LBP. The PENS therapy was
      also significantly more effective in improving physical activity, quality of
      sleep, and sense of well-being (P<.05 for each). The SF-36 survey confirmed that
      PENS improved posttreatment function more than sham-PENS, TENS, and exercise.
      CONCLUSIONS: In this sham-controlled study, PENS was more effective than TENS or
      exercise therapy in providing short-term pain relief and improved physical
      function in patients with long-term LBP.

PMID- 10071004
TI  - Postmarketing surveillance and adverse drug reactions: current perspectives and
      future needs.
AB  - Spontaneous reporting systems like MEDWATCH can be effective in revealing unusual
      or rare adverse events that occur with the use of medications, and such reports
      may often be sufficient to assign causality. However, spontaneous reports do not
      reliably detect adverse drug reactions (ADRs) that occur widely separated in time
      from the original use of the drug or that represent an increased risk of an
      adverse event that occurs commonly in populations not exposed to the drug. In
      these situations, spontaneous reports alone do not provide sufficient evidence to
      conclude that the adverse event was an ADR. Identification of ADRs associated
      with long-term administration of drugs for chronic diseases also remains
      problematic. Methods to evaluate ADRs using data from clinical trials, medical
      records, and computerized databases of medication users and nonusers must be
      developed to complement spontaneous reporting systems. Without these methods,
      potentially important ADRs will remain undetected, and spurious associations
      between adverse outcomes and medications or devices will remain unchallenged.

PMID- 10071005
TI  - The role of meta-analysis in the regulatory process for foods, drugs, and
      devices.
AB  - Synthesis of research findings has a long-standing tradition in science. While
      synthesis is currently required in the US food and drug regulatory process,
      formal meta-analysis may substitute for a pivotal study or broaden the
      generalizability of drug efficacy through a preplanned meta-analysis. Preplanned
      meta-analysis of individual trials with deliberately introduced heterogeneity may
      maximize the generalizability of results from randomized trials. Combining
      observational data may help to support an alternative claim or to quantify
      adverse events. In this setting, methods to address potentially greater sources
      of bias are required. Overall, meta-analysis adds evidence through the synthesis
      study findings and permits examination of how treatment effects vary across of
      subgroups, such as age and sex, and across study settings.

PMID- 10071006
TI  - Quality assurance in molecular genetic testing laboratories.
AB  - CONTEXT: Specific regulation of laboratories performing molecular genetic tests
      may be needed to ensure standards and quality assurance (QA) and safeguard
      patient rights to informed consent and confidentiality. However, comprehensive
      analysis of current practices of such laboratories, important for assessing the
      need for regulation and its impact on access to testing, has not been conducted.
      OBJECTIVE: To collect and analyze data regarding availability of clinical
      molecular genetic testing, including personnel standards and laboratory
      practices. DESIGN: A mail survey in June 1997 of molecular genetic testing
      laboratory directors and assignment of a QA score based on responses to genetic
      testing process items. SETTING: Hospital-based, independent, and research-based
      molecular genetic testing laboratories in the United States. PARTICIPANTS:
      Directors of molecular genetic testing laboratories (n = 245; response rate,
      74.9%). MAIN OUTCOME MEASURE: Laboratory process QA score, using the American
      College of Medical Genetics Laboratory Practice Committee standards. RESULTS: The
      245 responding laboratories reported availability of testing for 94 disorders.
      Personnel qualifications varied, although all directors had doctoral degrees. The
      mean QAscore was 90% (range, 44%-100%) with 36 laboratories (15%) scoring lower
      than 70%. Higher scores were associated with test menu size of more than 4 tests
      (P = .01), performance of more than 30 analyses annually (P = .01), director
      having a PhD vs MD degree (P = .002), director board certification (P = .03),
      independent (P <.001) and hospital (P = .01) laboratories vs research laboratory,
      participation in proficiency testing (P<.001), and Clinical Laboratory
      Improvement Amendment certification (P = .006). Seventy percent of laboratories
      provided access to genetic counseling, 69% had a confidentiality policy, and 45%
      required informed consent prior to testing. CONCLUSION: The finding that a number
      of laboratories had QA scores that may reflect suboptimal laboratory practices
      suggests that both personnel qualification and laboratory practice standards are
      most in need of improvement to ensure quality in clinical molecular genetic
      testing laboratories.

PMID- 10071007
TI  - Meta-analysis and epidemiologic studies in drug development and postmarketing
      surveillance.

PMID- 10071008
TI  - Report card on molecular genetic testing: room for improvement?

PMID- 10071009
TI  - Defining a "patients' bill of rights" for the next century.

PMID- 10071010
TI  - A patients' bill of rights: the medical student's role.

PMID- 10071011
TI  - Patients' rights proposals: the insurers' perspective.

PMID- 10071012
TI  - American independence and the right to emergency care.

PMID- 10071013
TI  - Going Hollywood with patient rights in managed care.

PMID- 10071014
TI  - Physician-legislators: physicians practicing public service.

PMID- 10071015
TI  - JAMA patient page: parenting.

PMID- 10071016
TI  - Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis
      after allogeneic blood stem cell transplantation.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de
      novo synthesis leading to impaired proliferation of activated lymphocytes.
      Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in
      preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow
      transplantation. We performed a pilot study evaluating the feasibility of the
      combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood
      stem cell transplantation. Toxicity and the bioavailability of MMF in this
      setting were investigated. METHODS: Fourteen patients who had received grafts
      from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined
      with intravenous CsA at 4 mg/kg starting at day-1. Plasma levels of mycophenolic
      acid (MPA) and its glucoronide were measured by high-performance liquid
      chromatography. Fifteen patients treated with a combination of CsA and
      methotrexate at the same institution were referred to as the control group.
      RESULTS: Trilineage engraftment was achieved in all study and control patients.
      Acute GVHD > or = grade II was observed in 46.5% and 60% of the study and control
      patients, respectively. No major differences in the rate of acute toxicities were
      detectable. The mean trough blood level of MPA in 10 patients was 0.28 microg/ml,
      and 5.7 microg/ml for MPA glucoronide. Reduced peak levels of MPA indicate a
      reduced absorption rate of MMF in the early posttransplant phase. CONCLUSIONS:
      The combined administration of MMF and CsA was shown to be feasible in patients
      after allogeneic blood stem cell transplantation. Because of the decreased
      bioavailability of MMF, dose-finding studies for an intravenous formulation are
      warranted.

PMID- 10071017
TI  - Sirolimus: a potent new immunosuppressant for liver transplantation.
AB  - BACKGROUND: Sirolimus (rapamycin) is a new immunosuppressant that appears to be
      synergistic with cyclosporine in kidney transplantation, but with a different
      side-effect profile. This pilot study evaluated sirolimus in liver
      transplantation. METHODS: Patients undergoing orthotopic liver transplantation
      for primary tumors (8), and later for nonmalignant disease (7), received one of
      three sirolimus-based immunosuppressive regimens. Protocol A comprised sirolimus,
      microemulsion cyclosporine (target whole blood concentration: 100 ng/ml), and
      prednisolone; protocol B omitted prednisolone; and protocol C was sirolimus
      alone. By 3 months after transplantation, all patients were receiving sirolimus
      as monotherapy. RESULTS: Fifteen patients were treated with a follow-up of 117
      806 days. Rejection was more common on monotherapy than double therapy, and
      absent on triple therapy. The drug was generally well tolerated, with only three
      patients discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis
      pneumonia, and one for inability to tolerate the taste of the drug. Two patients
      discontinued cyclosporine early, both as a result of neurological complications;
      they continued on sirolimus monotherapy. Five patients died; one suffered a
      cardiac arrest, and four died from sepsis in association with graft-versus-host
      disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary
      nonfunction. CONCLUSIONS: Sirolimus combined with cyclosporine provided potent
      immunosuppression of liver allografts, and sirolimus monotherapy was adequate and
      well tolerated as maintenance therapy. Side effects of sirolimus over the short
      period of follow-up were uncommon and reversible with dose reduction or cessation
      of therapy.

PMID- 10071018
TI  - Effect of systemic cyclosporine on tumor recurrence after liver transplantation
      in a model of hepatocellular carcinoma.
AB  - BACKGROUND: Long-term results after liver transplantation for hepatocellular
      carcinoma have been disappointing, largely because of the high recurrence rate.
      It is controversial whether the immunosuppressed state of the recipient
      contributes to this recurrence rate. We have developed a model in the rat system
      to examine the effect of immunosuppression on tumor recurrence after
      transplantation, as well as to evaluate other treatment strategies to decrease
      the recurrence rate. METHODS: A 2-mm3 nodule of Morris hepatoma 3924a was
      implanted intrahepatically at day 0. At postimplant day 16, the animals underwent
      syngeneic orthotopic liver transplantation. Two treatment groups were
      established. Group I received saline injections subcutaneously for 2 weeks, while
      group II received subcutaneous cyclosporine injections at 3 mg/kg/day for 14
      days. Animal survival, tumor recurrence rate, and sites of recurrence and number
      of pulmonary nodules were recorded. RESULTS: Overall survival rate was reduced in
      animals receiving cyclosporine. The mean survival time was 74.4 days (SEM 6.39
      days) in saline-treated animals and 50.4 days (SEM 7.63 days) in the cyclosporine
      treated animals. The proportion surviving in group 1 was 47% and in group 2 was
      18%. This difference in survival was statistically significant (P=0.025). The
      incidence of pulmonary nodules was increased in the cyclosporine-treated animals,
      and tumor recurrence in extrapulmonary sites was seen only in the cyclosporine
      treated animals. CONCLUSION: Results from this study suggest that cyclosporine
      has an adverse effect on tumor recurrence after transplantation. This model will
      be useful to further examine treatment strategies to improve the outcome of
      transplantation for hepatocellular carcinoma.

PMID- 10071019
TI  - Contribution of endothelin-1 to microcirculatory impairment in total hepatic
      ischemia and reperfusion injury.
AB  - BACKGROUND: Endothelin (ET)-1 may have a role in hepatic polymorphonuclear
      leukocyte infiltration as well as microcirculatory disturbance during hepatic
      ischemia-reperfusion (HIR) injury. This study was conducted to investigate the
      influence of ET-1 on the hepatic microcirculation after total HIR and to evaluate
      the effect of a nonselective ET receptor antagonist under these conditions.
      METHODS: Male rats pretreated with either normal saline (NS group) or TAK-044, a
      nonselective ET receptor antagonist (TAK group), were subjected to 120 min of
      total hepatic ischemia with extracorporeal portosystemic shunting. RESULTS:
      Plasma ET-1 levels increased significantly from 1 to 6 hr after reperfusion in
      the NS group when compared with the nonischemic control. In the early phase of
      reperfusion, the NS group showed significantly narrower sinusoids, lower hepatic
      tissue blood flow, a lower hepatic tissue oxy-hemoglobin concentration, and more
      hepatic neutrophil infiltration than the TAK group (P<0.05). Pretreatment with
      TAK-044 improved hepatic microcirculatory derangement, and resulted in
      significantly better 7-day survival (61.5%) with more bile production after
      reperfusion when compared with the NS group (P<0.01). CONCLUSIONS: The present
      study demonstrated that ET-1 is involved in the development of HIR injury by
      causing deterioration of the hepatic microcirculation. A nonselective ET receptor
      antagonist successfully ameliorated HIR injury through improvement of hepatic
      oxygenation and of the microcirculation along with reduced hepatic neutrophil
      infiltration.

PMID- 10071021
TI  - Antithrombin III treatment improves parameters of acute inflammation in a highly
      histoincompatible model of rat lung allograft rejection.
AB  - BACKGROUND: Antithrombin III (AT-III) is an antithrombotic agent with known anti
      inflammatory properties that is also known to attenuate acute inflammation,
      prevent ischemia-reperfusion injury, and disseminated intravascular coagulation
      (DIC) associated with sepsis and endotoxemia. Here, we examined the ability of AT
      III to modify parameters of acute inflammation in a highly histoincompatible
      model of rat lung allograft rejection (AR). METHODS: After left single lung
      transplantations (BN-->Lew), recipient animals were treated i.v. with 50 U/kg of
      human AT-III (low dose group), 500 U/kg of human AT-III (high dose group), or
      normal saline (control group) on days 2 and 4 posttransplant. All animals were
      sacrificed on day 6, and several pathological categories of acute inflammation
      related to AR were scored (0-4). The effect of AT-III on concanavalin A (Con A)
      stimulated rat spleen cell proliferation was also examined. RESULTS: The stage of
      AR, and the degrees of edema, hemorrhage, and necrosis were significantly reduced
      in the high dose group compared with the control group. AT-III significantly
      inhibited rat spleen cell proliferation in response to Con A, in a dose-dependent
      manner. Maximal inhibition was seen at 15 U/ml in culture. Identical inhibition
      of Con-A-stimulated cultures occurred in both serum free and serum-containing
      media, indicating that AT-III inhibition of Con-A-stimulated rat spleen cell
      proliferation is independent of its actions on thrombin. CONCLUSIONS: 1) AT-III
      treatment significantly improves parameters of acute inflammation seen in a
      highly histoincompatible model of rat lung AR. 2) AT-III inhibits in vitro T cell
      proliferation to the potent mitogen Con A, suggesting that protease inhibition
      may inhibit T cell activation in vitro. 3). The beneficial effects of AT-III on
      parameters of lung AR relate to the anti-coagulant, anti-inflammatory, and
      possibly immunoregulatory actions of AT-III.

PMID- 10071020
TI  - CTLA4IgG treatment induces long-term acceptance of rat small bowel allografts.
AB  - BACKGROUND: CTLA4 immunoglobulin (Ig)G that binds to B7 effectively inhibits the
      signaling of CD28/CTLA4-B7 pathway and induces antigen specific T cell
      unresponsiveness in vitro and in vivo. Using CTLA4IgG, we examined induction of
      long-term graft survival and the mechanism of maintenance of tolerance in rat
      allogeneic small bowel transplantation. METHODS: Small bowels of Brown-Norway
      rats (RT1n) were heterotopically transplanted into Lewis rats (RT1l). Recipients
      were treated with an i.p. injection of either CTLA4IgG or control IgG for 7 days.
      RESULTS: Long-term survival was observed in rats treated with CTLA4IgG, whereas
      control rats died within 16 days after transplantation. To examine whether a
      tolerant state was established in long-term survival rats, secondary
      transplantation was performed using small bowels of Brown-Norway rats or ACI
      (RT1b) rats. It was demonstrated that small bowels of Brown-Norway rats were
      accepted; however, those of ACI rats were rejected within 10 days. Serum
      concentrations of interleukin (IL)-4 were maintained at >50 microg/ml for 7 days
      after transplantation in rats treated with CTLA4IgG but <15 microg/ml in control
      rats. IL-2 concentration was reduced to half in CTLA4IgG-treated rats compared
      with that in control recipients. Serum IFN-gamma in CTLA4IgG-treated recipients
      increased after transplantation and was not distinguishable from that of control
      recipients during the first 7 days after transplantation. Conclusion. We
      demonstrated that CTLA4IgG treatment alone for 7 days induced a long-term donor
      specific tolerance in rat allogeneic small bowel transplantation. The induction
      of long-term acceptance of small bowel allografts by CTLA4IgG is not caused by
      simply the shift of anti-alloimmune responses from Thl to Th2 cytokine
      production.

PMID- 10071022
TI  - Twenty-four-hour preservation in gamma-hydroxybutyrate improves lung function in
      a canine single-lung allotransplantation.
AB  - BACKGROUND: We investigated the effect of gamma-hydroxybutyrate (GHB) when added
      to the low-potassium University of Wisconsin (LPUW) solution used for the
      preservation of canine lung for 24 hr. We also examined the effect of
      pretreatment of donor and recipient dogs with GHB on lung function after
      transplantation. METHODS: Two groups were investigated. In the LPUW group, donor
      lungs were flushed with LPUW solution without GHB. In the GHB group, donor and
      recipient dogs were pretreated with GHB, and donor lungs were flushed with LPUW
      containing GHB. RESULTS: Posttransplant graft function was best in the GHB group.
      At 1 hr after reperfusion, PaO2 in the GHB group (475.7+/-96.2 mmHg) was
      significantly higher than in the LPUW group (188.3+/-102.7 mmHg, P<0.05).
      Furthermore, the use of GHB resulted in a significant increase in lung compliance
      (28.3+/-6.5 ml/cm H2O) compared with LPUW group (21.5+/-2.8 ml/cm H2O).
      CONCLUSIONS: Our results suggest that GHB is potentially useful for functional
      improvement of hypothermically preserved canine lung allografts after
      reperfusion.

PMID- 10071023
TI  - Correlation between angiotensin-converting enzyme gene insertion/deletion
      polymorphism and kidney graft long-term outcome in pediatric recipients: a single
      center analysis.
AB  - BACKGROUND: Despite numerous advances in the areas of organ preservation,
      histocompatibility, and immunosuppression, chronic deterioration of organ
      allograft function, referred to as "chronic rejection," still remains the main
      obstacle to long-term graft survival. The common feature of chronic rejection is
      a concentric generalized graft arteriosclerosis associated with interstitial
      fibrosis that reflects an allogeneic injury to graft arteries, possibly worsened
      by other alloantigen-independent risk factors. The presence of the angiotensin I
      converting enzyme (ACE) gene-deleted (D) allele has been associated, when in
      homozygosity, with increased risk of cardiovascular diseases and with an
      accelerated progression of organ damage in a variety of kidney diseases. In this
      study, we analyzed whether the insertion/deletion polymorphism of the ACE gene,
      because of its negative prognostic impact on cardiovascular and renal pathology,
      could have any influence on kidney graft survival in pediatric recipients.
      METHODS: DNA was isolated from peripheral blood mononuclear cells from 146
      pediatric dialysis patients (mean age: 12.9 years) who received a first kidney
      graft at our center between December 1985 and July 1997. To rule out any bias due
      to acute graft losses, only 119 patients who reached a minimum of 12 months of
      graft survival were considered for statistical analysis. The insertion/deletion
      polymorphism of the ACE gene was detected using a polymerase chain reaction
      technique with two flanking primers. RESULTS: The results demonstrated that (i)
      the distribution of DD and non-DD (ID + II) genotypes was 36.1% (43 patients) and
      63.8% (76 patients), respectively; (ii) actuarial graft survival at 7, 8, 9, and
      10 years in patients with non-DD genotype was significantly higher than that in
      patients with DD genotype (7 years: 94.6% vs. 72.4%, P<0.05; 8 years: 94.6% vs.
      62%, P<0.025; 9 years: 87.3% vs. 51.4%, P<0.025; 10 years: 76.3% vs. 25.7%,
      P<0.01). CONCLUSIONS: In conclusion, the above data indicate that DD genotype is
      associated in pediatric kidney graft recipients with a shorter long-term kidney
      graft survival and suggest a possible role of this genotype as a cofactor in the
      progression of nonimmunological injuries leading to chronic kidney graft failure.

PMID- 10071024
TI  - FK506-associated thrombotic microangiopathy: report of two cases and review of
      the literature.
AB  - BACKGROUND: FK506 is a recently developed immunosuppressant that has been useful
      in improving the survival of transplanted organs. Among the numerous adverse side
      effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent
      but severe complication. METHODS: We report two cases of FK506-associated TMA and
      review the 19 previous reported cases. RESULTS: From these 21 cases, the reported
      incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in
      females, and the mean age at presentation is 47 years. Eighty-one percent of the
      cases occurred in patients with kidney allografts, and the remaining patients had
      liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an
      average interval of 9.3 months from the time of transplantation. Patients may be
      asymptomatic or may present with the full-blown picture of hemolytic uremic
      syndrome. All patients had an elevated serum creatinine level but did not always
      show signs of hemolysis. Trough levels of FK506 were not predictive for the
      development of TMA, but generally a reduction of drug dose correlated with kidney
      function improvement and disappearance of the hemolytic picture. The renal
      allograft biopsy provided a conclusive diagnosis in all 17 cases in which this
      procedure was performed. Treatment, which mainly consisted of reduction or
      discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh
      frozen plasma exchange, resolved TMA in most patients (57%). However, in one of
      these patients (5%), the graft was subsequently lost due to causes unrelated to
      TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost
      the graft due to acute rejection and persistent TMA, and three other patients
      (14%) who had bone marrow, heart, and liver transplants, died of multiple organ
      failure, probably unrelated to TMA. In the remaining four patients (19%),
      response to treatment was not reported. CONCLUSIONS: TMA must be considered in
      organ transplant patients treated with FK506 whenever kidney function
      deteriorates, even in the absence of microangiopathic hemolytic anemia. Although
      TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney
      function or even the patient's death.

PMID- 10071025
TI  - Safety of kidney biopsy in pediatric transplantation: a report of the Controlled
      Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study
      Group.
AB  - BACKGROUND: Historically, young children undergoing renal transplantation have
      lower allograft survival than adults, and potential causes of this are being
      addressed by the North American Pediatric Renal Transplant Cooperative Study
      through the National Institutes of Health-sponsored study Cooperative Clinical
      Trials in Pediatric Transplantation. Included in this study is evaluation of
      surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data
      exist in children to identify the risk involved with renal transplant biopsies.
      METHODS: Questionnaires were mailed to 21 participating centers asking for
      descriptions of adverse events associated with kidney biopsies, with choices
      limited to none, gross hematuria, perinephric hematoma, and other. Further
      clinical details were obtained from review of medical records of all patients
      with reported adverse events. Data were collected from 19 centers on 126
      patients. RESULTS: Eighty-six patients had undergone 212 biopsies (75 SB and 137
      CB). Nine biopsy-related adverse events were reported (4.2%): three SB (4.0%) and
      six CB (4.4%). Gross hematuria was reported in six patients (2.8%): two SB (2.7%)
      and four CB (2.9%). A perinephric hematoma was reported in one patient. Two
      patients with intraperitoneal kidneys developed significant bleeding after biopsy
      and required transfusions and surgical exploration. No patient lost kidney
      function or required nephrectomy after biopsy. No difference was noted in adverse
      events between SB at day 5 or 12 versus CB. CONCLUSION: Evaluation of
      transplanted kidney tissue may provide important information for the care of the
      transplantation patient. This analysis suggests that transplanted kidney biopsies
      can be performed with minimal risks in pediatric patients.

PMID- 10071026
TI  - A practical approach to evaluate the potential donor pool and trends in cadaveric
      kidney donation.
AB  - BACKGROUND: The potential supply of transplantable cadaver kidneys is often
      expressed as donors per million population (pmp), which ignores some essential
      factors governing organ donation. METHODS: We performed a modeled analysis of
      kidney donor extraction rates by age, gender, race, cause of death, geographic
      region, and year in a cohort of evaluable deaths and actual cadaver donors
      between the ages of 1 and 65 years (1988-1993). Evaluable death was defined as an
      in-hospital death in patients between the ages of 1 and 65 years whose ICD-9-CM
      cause of death was not an obvious contraindication to kidney donation. The main
      outcome measures were the crude donation rate and an adjusted donor extraction
      rate (DER) per 1000 evaluable deaths. RESULTS: A total of 1.4x10(6) in-hospital
      deaths produced 300,502 evaluable deaths and 20,575 actual donors. Between 1989
      and 1993, DER increased from 61.1 to 75 per 1,000 evaluable deaths. DERs were
      highest among the youngest age groups, declining significantly with age from
      405.0 to 16.7/1,000 evaluable deaths for age groups 1-10 and 56-65 years,
      respectively. There was a small difference in donors pmp between blacks and
      whites (15 vs. 18). In contrast, DER was seven times higher in whites compared
      with blacks (112.5 vs. 16.5/1,000 evaluable deaths; P<0.001). The crude donation
      rate (per 1,000 evaluable deaths) was high for stroke (604.8) and trauma-related
      deaths (230.6), resulting in highly efficient donor extraction from these deaths.
      Region-specific DERs ranged from 49.4 to 83/1,000 evaluable deaths and differed
      significantly from the corresponding donors pmp. CONCLUSIONS: Estimating kidney
      donation relative to in-hospital evaluable deaths is a meaningful measure of
      organ procurement efficiency. Efforts to enhance cadaveric kidney donation should
      seek to understand and reduce the marked demographic and regional disparity in
      donor extraction rates.

PMID- 10071027
TI  - Long-term impact of superinfection by hepatitis G virus in hepatitis C virus
      positive renal transplant patients.
AB  - BACKGROUND: The hepatitis G virus (HGV) has been recently cloned. Studies in
      immunocompetent patients have shown that HGV superinfection in hepatitis C virus
      (HCV)-positive patients does not affect (i) clinical presentation, HCV RNA level,
      or response to interferon-alpha therapy; or (ii) the histopathologic severity and
      characteristics of chronic hepatitis. No data are currently available on the
      impact of HGV infection on liver histology of renal transplant (RT) patients
      although the reported prevalence of serum HGV RNA in this population is high,
      ranging from 14% to 55%. PATIENTS AND METHODS: We determined the prevalence of
      HGV infection in 103 HCV-positive RT patients for whom HGV RNA was
      retrospectively determined by reverse transcription-polymerase chain reaction
      before, at the time of, and after transplantation (last follow-up). We evaluated
      the impact of HGV on liver function tests, liver histology (by means of the
      Knodell score), and renal parameters such as the prevalence of acute rejection
      and renal function. RESULTS: A total of 29 (28%) of the HCV-positive RT patients
      had a positive HGV RNA (group 1). The mean duration of HGV infection was at least
      119+/-64 months (range: 18-240 months). Group 1 patients were compared to the 74
      HGV RNA-negative/HCV-positive RT patients (group 2). Liver histology showed a
      significantly lower degree of fibrosis in group 1 (0.4+/-0.5) than in group 2
      (1+/-1.2; P=0.02); two patients from group 2 but none from group 1 had overt
      cirrhosis. Conversely, the extent of hepatic inflammation and hepatocellular
      destruction was not statistically different between the two groups. The number of
      patients who experienced at least one acute rejection episode was significantly
      higher in group 1 (69%) than in group 2 (42%; P=0.01). However, the multivariate
      analysis did not identify the presence of HGV RNA at the time of renal
      transplantation as an independent factor of acute rejection; conversely, (i) the
      occurrence of cytomegalovirus infection or disease and (ii) the duration of HCV
      infection significantly increased the likelihood of having acute rejection.
      CONCLUSIONS: This study shows that: (i) HGV infection was often present when the
      patients seroconverted for HCV, (ii) HGV RNA-positive/HCV-positive RT patients
      experienced acute rejection more frequently than HGV RNA-negative/HCV-positive RT
      patients, and (iii) HGV infection seems to have no detrimental effect upon liver
      enzymes or liver histology in HCV-positive RT patients.

PMID- 10071028
TI  - Early proteinuria in renal transplant recipients treated with cyclosporin.
AB  - PURPOSE: To establish the risk profile for the development of proteinuria in the
      first months after renal transplantation and to disclose the prognostic
      significance of this finding. DESIGN: We conducted an observational historic
      cohort study. SETTING: We conducted the study in a tertiary care hospital renal
      transplantation unit covering a potential population of approximately 2 million.
      We made extensive use of suboptimal donors. POPULATION: In our unit, 560
      cadaveric renal transplants were performed between January 1988 and June 1997,
      under Cyclosporine immunosuppression, with a minimum follow up of 1 year. METHOD:
      The risk profile analysis explored early clinical factors reported to be related
      to the late course of renal transplantation. The study of the prognostic
      significance of proteinuria included survival analysis and correlation with late
      markers of graft dysfunction, taking into consideration the intensity and
      persistence of early proteinuria. A multivariate approach was used in all cases.
      RESULTS: Early proteinuria was strongly associated with delayed graft function
      (odds ratio [OR] 1.03/day of dialysis), acute rejection (OR 1.7 for steroid
      sensitive and 6.2 for steroid-resistant rejection), renal transplant to a
      hypersensitized recipient (OR 2.5), and pediatric (<5 years)(OR 4.1) or older
      (>60 years)(OR 3.0) donors. The predictive model for persistency of proteinuria
      was very similar, whereas transient proteinuria could not be adequately modeled.
      Increasing intensity of proteinuria was strongly associated with poor patient and
      graft survival. Persistent, but not transient, proteinuria supported this
      relationship. CONCLUSIONS: Proteinuria appearing early after renal
      transplantation is strongly associated with delayed graft function, acute
      rejection, and the use of pediatric or older donors. Whatever its background,
      proteinuria is a strong predictor of poor patient and graft survival. This effect
      is directly related to the intensity and persistence of the disorder.

PMID- 10071029
TI  - Postoperative flow cytometry crossmatch in living donor liver transplantation:
      clinical significance of humoral immunity in acute rejection.
AB  - BACKGROUND: The role of humoral immunity in acute rejection in solid organ
      transplantation remains controversial, although it is known that the presence of
      antidonor antibodies may precipitate graft rejection. We investigated the
      clinical relevance of antidonor humoral immunity for living donor liver
      transplantation (LDLT) by means of flow cytometry crossmatch (FCXM). METHODS: T
      cell FCXM using fresh donor peripheral lymphocytes was performed before and up to
      1 month after LDLT in 58 patients. Ten patients received ABO-incompatible grafts.
      IgM and IgG antidonor antibodies were analyzed in relation to clinical acute
      rejection as defined by liver function tests with or without histological
      evidence. RESULTS: Pretransplantation FCXM was positive for five patients (8.6%),
      resulting in two cases of positive posttransplantation FCXM and two rejection
      episodes. Twelve patients (20.7%) showed positive posttransplantation FCXM. The
      incidence of acute rejection within 1 month was 100% in FCXM-positive patients
      and 17.4% in FCXM-negative patients (P<0.001). Thirteen (76.5%) of 17 rejection
      episodes in ABO-compatible cases were associated with concomitant antidonor IgM
      antibody. IgG antibody was also identified in six of these episodes. Antidonor
      antibodies disappeared after rejection treatments in all cases, but with some
      delay in clinical improvement. On the other hand, no antidonor antibodies were
      detected in any of the four rejection episodes in ABO-incompatible cases.
      CONCLUSIONS: Early acute rejection in LDLT is significantly associated with
      antidonor T cell antibody formation in ABO-compatible cases. This suggests a
      definite role for donor-specific humoral immunity in acute rejection. Rejection
      episodes without antidonor antibodies may suggest graft injury by pure cellular
      immunity, or possibly the presence of humoral immunity triggered by antigens not
      present on donor T cells.

PMID- 10071030
TI  - The vanishing importance of age in renal transplantation.
AB  - BACKGROUND: The growing number of patients awaiting a kidney transplant raises
      questions about allocation of kidneys to the elderly and about the use of elderly
      donors. In all reported studies analyzing the influence of age on the outcome
      after renal transplantation, age is investigated as a categorical variable.
      METHODS: We studied age both as a categorical (Kaplan-Meier) and as a continuous
      (Cox) variable in a total of 509 cyclosporine-treated recipients of a primary
      cadaveric kidney graft who underwent transplantation between July 1983 and July
      1997. For the Kaplan-Meier analysis, the population was divided into three
      comparably sized age groups: 17-43 years (n=171), 44-55 years (n=169), and 56-75
      years (n=169). RESULTS: Patient survival was better and graft survival censored
      for death was worse in the younger patients. Overall graft survival (end point
      was death or graft failure) was not significantly influenced by age. In the Cox
      proportional hazards analysis, transplantation year turned out to be an
      important, independent variable influencing all end points. Because the influence
      was not linear, three periods were defined in which the relative risk remained
      stable: 1983-1990, 1991-1993, and 1994-1997. In the second period, the relative
      risk for transplant failure or death was 49% of that in the first period. In the
      third period, the relative risk had decreased to 22% of that in the first period.
      Recipient age and donor age were significant predictors of overall transplant
      failure. There was no interaction between these variables and transplantation
      year. Within each transplantation period, an increase in recipient age by 1 year
      increased the relative risk for overall graft failure by only 1.44%. The
      influence of donor age followed a J-shaped curve with a minimum at 30 years. The
      influence of increasing either recipient or donor age was counteracted by the
      improving results over time. CONCLUSION: Considering the improving results over
      time, there are, at this moment, no arguments for an age restriction for kidney
      transplant recipients or donors.

PMID- 10071031
TI  - Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts.
AB  - BACKGROUND: Apoptosis is a cellular phenomenon generally found within rejecting
      transplants. It may play a role in physiological or therapy-associated deletion
      of infiltrating lymphocytes or in graft cell destruction. Our study focuses on
      apoptosis of infiltrating lymphocytes during acute kidney rejection after the
      initial steroid pulse therapy and on possible prognostic implications. METHODS:
      Renal biopsy specimens of 23 transplant recipients with acute tubulo-interstitial
      rejection were examined for appearance of apoptosis and compared with 11
      transplant biopsies with unspecific organ injury accompanied by lymphocyte
      infiltration. In all patients, biopsies were performed after steroid pulse
      therapy, and, after confirmation of rejection, antilymphocytic antibody treatment
      was carried out. Apoptosis was determined via terminal
      deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling analysis
      and confirmed by electron microscopy. RESULTS: Apoptosis of lymphocytes or of
      tubular epithelium was detected in 11 cases of acute rejection (48%),
      respectively. Four biopsies showed lymphocytic as well as tubular apoptosis,
      whereas five sections showed no signs of programmed cell death. In biopsies
      revealing unspecific injury, tubular cell apoptosis was more frequently found
      (73%) compared with lymphocyte apoptosis (27%, P<0.05). Most interestingly,
      patients with a beneficial recovery from acute rejection had a higher proportion
      of lymphocyte apoptosis compared with patients with poor rejection outcome. The
      Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without
      counter-regulating apoptosis. CONCLUSIONS: Lymphocyte apoptosis is found as
      frequently as tubular cell apoptosis in rejecting renal grafts after steroid
      pulse therapy and might have prognostic value for rejection outcome.

PMID- 10071032
TI  - Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in
      simultaneous pancreas-kidney transplantation: initial experience in 50
      consecutive cases.
AB  - BACKGROUND: The current study examines the use of mycophenolate mofetil (MMF) and
      tacrolimus as primary immunosuppression in simultaneous pancreas-kidney (SPK)
      transplantation. In addition, analyses of the rates of conversion from one
      immunosuppressive agent to another, and its subsequent consequences with respect
      to outcomes were determined. Quality of graft function, infections, and effect on
      preexisting essential hypertension are also described. METHODS: Immunosuppression
      consisted of quadruple therapy with antithymocyte globulin induction, tacrolimus,
      MMF, and prednisone. Patient and graft survival and rejection rates in 50
      consecutive SPK recipients, followed for a minimum of 3 months and a mean of 14
      months (range: 3-34 months), are described. RESULTS: Thirty-nine of 50 (78%)
      patients tolerated the MMF/tacrolimus combination long-term (mean duration of
      follow-up: 14+/-7 months). Nine of 50 patients (18%) were converted to Neoral,
      and 4 patients were converted to azathioprine as a substitute for MMF. The 2-year
      actuarial patient, kidney, and pancreas survival rates were 97.7%, 93.3%, and
      90.0%, respectively. At 6 months after transplant, the overall incidence of acute
      rejection was 16%. There was a statistically significant (P< or =0.04, Cox-Mantel
      test) difference in the rate of rejection associated with conversion to Neoral.
      The incidence of rejection 6 months after transplant in the group maintained on
      MMF/tacrolimus was 10.2% vs. 44.4% in the group converted to Neoral (P< or =0.04,
      Cox-Mantel test). Overall, the 1-year actuarial cumulative incidence of tissue
      invasive cytomegalovirus disease was 6.6%. There were no cases of fungal
      infections or post-transplant lymphoproliferative disorders. One patient
      developed Kaposi's sarcoma 10 months after transplant. With respect to
      hypertensive disease, 60% (12/20) of the patients who required pharmacologic
      control of blood pressure before transplant were off all antihypertensive
      medications at 1 year after transplant. An additional 20% (4/20) of patients had
      a reduction in the number of medications required to control blood pressure at 1
      year after transplant. CONCLUSIONS: We conclude that the combination of MMF and
      tacrolimus as primary immunosuppression for SPK transplantation results in
      excellent patient and graft survival rates, a very low rate of acute rejection,
      and low rates of infection and malignancy.

PMID- 10071033
TI  - Prolonged survival of corneal allografts incubated in alloantibody fragments.
AB  - BACKGROUND: In this study, we determined the binding characteristics of F(ab')2
      alloantibody fragments to corneal antigens and assessed the capacity of these
      antibody fragments to protect corneal allografts from immune attack. METHODS:
      Goat anti-rabbit alloantibodies were pepsin-digested and labeled with 125I, and
      the time course of association and dissociation of the F(ab')2 fragments was
      determined. Corneal allografts were incubated in unlabeled F(ab')2 fragments and
      transplanted into allogeneic recipients, and the graft survival times were
      recorded. RESULTS: Binding of radiolabeled F(ab')2 fragments to rabbit cornea
      cells reached a maximum at 12 hr. At 32 degrees C (rabbit corneal temperature),
      the radiolabel eluted rapidly from the cornea, reaching baseline at 72 hr. At 4
      degrees C (corneal graft storage temperature), significant amounts remained
      associated with the cornea at 96 hr. Mean survival time for grafts incubated in
      F(ab')2 anti-rabbit fragments was significantly greater than that of grafts
      incubated in nonimmune F(ab')2 fragments. Three of the corneal allografts
      incubated in goat F(ab')2 anti-rabbit fragments survived for 100 days, whereas
      the longest surviving control allograft incubated in goat F(ab')2 nonimmune
      fragments was rejected on day 24. Preincubation of corneas in unlabeled, immune
      F(ab')2 fragments followed by incubation in radiolabeled, immune F(ab')2
      fragments suggested that antigen masking was not a factor in the prolongation of
      graft survival. CONCLUSION: Based on the binding and release kinetics and the
      graft survival times, it appears that the protective effect of immune F(ab')2
      fragments extends well beyond the binding interval of the antibody fragments to
      corneal cell membranes.

PMID- 10071034
TI  - Suppression of allograft rejection with anti-alphabeta T cell receptor antibody
      in rat corneal transplantation.
AB  - BACKGROUND: Anti-alphabeta T cell receptor monoclonal antibody (R73) has been
      reported to be a potent immunosuppressant. The suppressive effects of this
      antibody on allograft rejection after corneal transplantation are unknown.
      METHODS: Orthotopic rat penetrating keratoplasty was performed using Lewis rats
      as recipients and Brown Norway and Fisher rats as donors. The treated groups
      received R73 intraperitoneally until day 12 after the transplantation. In grafted
      rats with or without R73 treatment, cytokine expression of the aqueous humor,
      corneal-infiltrating cells, draining lymph nodes, and splenocytes was determined.
      Delayed-type hypersensitivity (DTH) responses were compared. RESULTS: All
      allografts in the untreated controls of Fisher-to-Lewis or BN-to-Lewis rat
      combinations were rejected within 14 days. In contrast, indefinite survival rates
      of the postoperative R73-treated group increased to 86% in the Fisher-to-Lewis
      and 23% in the Brown Norway-to-Lewis combinations, respectively. Interferon-y,
      interleukin (IL)-2 (T helper [Th]1), and IL-10 (Th2), but not IL-4 (Th2),
      expression of the eye and DTH responses in the control group were suppressed in
      the R73-treated group. Both IL-2 and IL-10 expression after mixed lymphocyte
      culture in the R73-treated group were significantly lower than those of the naive
      and untreated control group. CONCLUSIONS: alphabeta T cell receptor-targeted
      therapy prevents allograft rejection in rat corneal transplantation as evidenced
      by suppression of DTH responses. The cytokine profile after R73 treatment was
      characterized by low interferon-gamma, IL-2, and IL-10, and high IL-4 expression.

PMID- 10071035
TI  - Induction of specific tolerance to allografts in rats by therapy with non
      mitogenic, non-depleting anti-CD3 monoclonal antibody: association with TH2
      cytokines not anergy.
AB  - BACKGROUND: Anti-CD3 monoclonal antibodies (mAb) are potent immunosuppressives in
      transplantation but most do not induce tolerance. They induce anergy in Th1 cells
      but, if they bind to Fc receptors on antigen presenting cells, they activate T
      cells to release cytokines. METHODS: This study examined the mechanisms of
      transplant tolerance induction to PVG fully allogeneic grafts in dark agouti rats
      by G4.18, a mouse immunoglobulinG3 anti-rat CD3 mAb that does not bind rat Fc
      receptors. Evidence of T cell activation was assayed by flow cytometry, reverse
      transcription (RT)-polymerase chain reaction (PCR) for cytokine mRNA, and
      responsiveness in mixed lymphocyte culture. RESULTS: G4.18 treatment modulated T
      cell receptor/CD3 and CD2 and depleted T cells by <20% but did not induce
      activation surface markers. mRNA for interleukin (IL)-2, interferon (IFN)-gamma,
      tumor necrosis factor (TNF)-alpha, and IL-4 in the lymph node, spleen, and thymus
      was not increased, and IFN-gamma mRNA was reduced. G4.18-treated and naive rat
      cells had similar proliferation and expression of IL-2, IFN-gamma, and IL-4 in
      vitro. G4.18-treated allograft recipients had no induction of mRNA for IL-2, IFN
      gamma, TNF-alpha, TNF-beta, IL-4, IL-5, IL-10, perforin, and granzyme A & B in
      the spleen or grafts, with levels similar to those in isografts. The IL-4 and IL
      5 mRNA levels in the spleen but not the graft of G4.18-treated recipients were
      higher than in rejecting and naive animals. Cells from G4.18-treated graft
      recipients proliferated more rapidly to the donor than to the third party and had
      increased IL-4 expression. CONCLUSIONS: G4.18 induced transplant tolerance by a
      combination of modulation and blocking of the TCR/CD3, associated with increased
      Th2 cytokines, without depletion, induction of anergy, or nonspecific activation
      of T cells.

PMID- 10071036
TI  - Tacrolimus induces increased expression of transforming growth factor-beta1 in
      mammalian lymphoid as well as nonlymphoid cells.
AB  - BACKGROUND: We and others have reported that cyclosporine (CsA) induces increased
      expression of transforming growth factor-beta1 (TGF-beta1) in vitro as well as in
      vivo. In view of similarities between tacrolimus and CsA with respect to
      immunosuppressive mechanisms, we determined whether tacrolimus, in a fashion
      similar to CsA, induces TGF-beta1 hyperexpression in mammalian cells. METHODS: We
      studied the induction of TGF-beta1 mRNA by tacrolimus using reverse transcription
      polymerase chain reaction and Northern blot analysis in normal human T cells and
      A-549 cells (human lung adenocarcinoma cell line), a cell line used to study the
      biology of TGF-beta and the induction of TGF-beta1 by CsA. We also measured the
      induction of TGF-beta1 protein by tacrolimus in activated human T cells,
      peripheral blood mononuclear cells, and A-549 cells, using sandwich enzyme-linked
      immunosorbent assay. RESULTS: A significant increase in the TGF-beta1 mRNA
      expression was observed after treatment of T cells or A-549 cells. Tacrolimus
      treatment resulted also in heightened production of TGF-beta1 protein by
      activated T cells, A-549 cells, or peripheral blood mononuclear cells activated
      with anti-CD3, phytohemagglutinin, and concanavalin A. CONCLUSIONS: Our
      observations that tacrolimus stimulates TGF-beta1 hyperexpression in mammalian
      cells suggest a unifying mechanism for the immunosuppressive as well as
      nephrotoxic properties of tacrolimus, as the multifunctional TGF-beta1 is a
      potent immunosuppressive and fibrogenic cytokine.

PMID- 10071037
TI  - Ex vivo depletion of T cells from bone marrow grafts with CAMPATH-1 in acute
      leukemia: graft-versus-host disease and graft-versus-leukemia effect.
AB  - BACKGROUND: Preventing graft-versus-host disease (GVHD) by depletion of T
      lymphocytes from the stem cell graft for transplantation remains controversial,
      mainly because of the perceived increase in disease recurrence. METHODS: We
      retrospectively analyzed the outcome of 50 consecutive individuals in remission
      of acute lymphoblastic leukemia (n=13; 8 in complete remission [CR]1) or acute
      myeloblastic leukemia (n=37; 33 in CR1), who had received marrow grafts from HLA
      identical siblings. The conditioning regimen included six 2-Gy fractions of total
      body irradiation, succeeded by cyclophosphamide at 120 mg/kg (with mesna)
      followed by four fractions of 1.5 Gy to lymphoid areas. Bone marrow (n=38) or
      peripheral blood mobilized donor mononuclear cells (n=12) were exposed ex vivo to
      CAMPATH-1 (IgM and complement, or IgG; antiCD52) antibodies, without any further
      posttransplantation immunosuppression. RESULTS: Median patient age was 31 (range
      14-51) years; 12 patients were 40 or older. Thirty-two patients were male. One
      patient died of pulmonary hemorrhage on day 10; another died on day 29 of
      interstitial pneumonitis. Except for one early death, all patients engrafted. Ten
      (21%) of the remaining 48 who were at risk, developed GVHD. In none was it
      greater than grade II. Eight patients developed serious viral infections. Four
      died of cytomegalovirus pneumonia, adenovirus hepatitis, and human
      immunodeficiency. Overall, 11 patients (22%) relapsed (4 of 33 acute myeloblastic
      leukemia in CR1) at a median of 235 (range 46-528) days. Mean posttransplantation
      follow-up was 1062 (median 560; range 10-4177) days. Thirty-three patients (66%)
      remained disease free at a mean of 1,118 (median 1439; range 159-4,177) days. For
      all patients, the performance status was between 82% and 100% (median 100).
      CONCLUSION: T-cell depletion with CAMPATH-1 effectively prevents GVHD,
      particularly the severe acute forms, without leading to excessive risk of relapse
      in acute leukemia.

PMID- 10071038
TI  - Hepatitis C virus in peripheral blood mononuclear cells from a chronically
      infected patient receiving liver graft from infected donor.
AB  - BACKGROUND: In hepatitis C virus (HCV)-positive patients receiving HCV-positive
      liver allografts either the donor or recipient strain overtakes the other strain.
      Whether these changes are reflected in peripheral blood mononuclear cell (PBMC)
      associated virus is unknown. METHODS: We analyzed by single-strand conformation
      polymorphism and sequencing HCV RNA from serum and PBMCs from a liver transplant
      recipient whose indigenous strain was replaced by the donor strain. RESULTS: Only
      the recipient strain was detectable in serum and PBMCs 3 and 5 days after
      transplantation; at day 7 and 8, a mixture of both was present in the PBMCs, but
      only recipient strain was detectable in serum. This coincided with the peak
      presence of donor DNA in recipient PBMCs. From day 14 on, HCV sequences in serum
      and PBMCs were indistinguishable. CONCLUSIONS: Overtake phenomenon in the setting
      of liver transplantation from infected donors to infected recipients is
      manifested in PBMCs. Cells released from infected graft carry donor HCV strain.

PMID- 10071039
TI  - Autologous bone marrow transplantation for recurrent malignant lymphoma after
      liver transplantation.
AB  - BACKGROUND: Cancer chemotherapy in chronic carriers of hepatitis B virus is known
      to promote viral replication, and, when immunosuppressive treatment is stopped,
      the return of immune competence can be followed by a fulminant hepatitis. Liver
      transplantation may be required and has been successfully performed for this
      condition. However, malignancy recurrence after transplantation has not been
      reported yet. METHODS AND RESULTS: We here report the case of an asymptomatic
      hepatitis B surface antigen carrier who developed a malignant lymphoma, which was
      treated by chemotherapy. After cessation of chemotherapy, he developed a
      fulminant hepatitis, requiring liver transplantation. Three years later, he
      developed a recurrent malignant lymphoma, which was treated successfully by
      autologous bone marrow transplantation. In order to prevent viral replication,
      lamivudine and intermittent administration of fresh-frozen plasma highly
      concentrated in anti-HBs immunoglobulin was initiated before the bone marrow
      transplantation. The patient remains well 12 and 56 months after autologous bone
      marrow and liver transplantation, respectively. CONCLUSIONS: This experience
      suggests that all hepatitis B surface antigen-positive patients for whom
      chemotherapy is indicated would benefit from prophylactic antiviral hepatitis B
      virus therapy. Furthermore, successful autologous bone marrow transplantation is
      possible after liver transplantation.

PMID- 10071040
TI  - Favorable nutritional outcome after isolated liver transplantation for liver
      failure in a child with short bowel syndrome.
AB  - A patient with short gut syndrome presented with end-stage liver disease. She
      underwent an isolated liver transplantation at the age of 3.5 years. Parenteral
      nutrition was discontinued 1.5 years after surgery. At 7 years of age, the
      patient has maintained normal nutritional indices and growth while on a normal
      oral diet. This observation suggests that liver transplantation alone can be a
      valuable alternative to the combined small bowel/liver transplantation in short
      bowel syndrome when intestinal adaptation is expected and if the ileocecal valve
      is present and that improvement of gut function can occur after successful liver
      transplantation.

PMID- 10071041
TI  - Soluble forms of CD95 and CD95 ligand after living related liver transplantation.
AB  - BACKGROUND: Soluble forms of CD95 and CD95 ligand (sCD95 and sCD95L,
      respectively) can increase in the serum of patients with some inflammatory
      disease. In this study, we investigated the serum levels of sCD95 and sCD95L in
      liver transplantation recipients. METHODS: Serum levels of sCD95 and sCD95L in
      living related liver transplant recipients were analyzed by ELISA and their
      relation to the clinical findings estimated. RESULTS: Serum samples from the
      recipients did not show detectable levels of sCD95L but showed significantly
      increased levels of sCD95. The increase of sCD95 was positively associated with
      that of total-bilirubin and incidence of rejection, infection, and graft
      ischemia. CONCLUSIONS: The present results indicate an existence of sCD95 in the
      recipients of living related liver transplants. The increased serum levels of
      sCD95 may modify the immunological situation of the recipients after
      transplantation or represent the ongoing graft damage.

PMID- 10071042
TI  - Inhibition of complement-mediated immune hemolysis by peptides derived from the
      constant domain of immunoglobulin.
AB  - High-dose administration of intravenous immunoglobulin is reported to be useful
      for inhibiting complement-dependent immune cytolysis. We have found that, among
      the proposed C1q-binding sites of the Fc portion of human IgG1, only residues 282
      292 inhibited pig red blood cell lysis by human serum. Moreover, a hexadecemeric
      multiple antigen peptide of residues 282-292 from IgG showed significantly
      greater activity in suppressing complement-mediated immune cytolysis and can be
      used in place of high-dose intravenous immunoglobulin, which is extracted from
      donors and thus is expensive.

PMID- 10071043
TI  - Detection of viral genomas in serum samples from potential organ donors.

PMID- 10071044
TI  - Status epilepticus and cardiac transplantation.

PMID- 10071045
TI  - A renal allograft recipient with late recurrence of focal and segmental
      glomerulosclerosis after switching from cyclosporine to tacrolimus.
AB  - BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is one of the most
      frequent and severe primary glomerulonephritis that recurs in transplanted
      kidneys. Although cyclosporine seems to have no effect on the frequency of FSGS
      recurrence, there is evidence that cyclosporine reduces proteinuria and prolongs
      graft survival in patients with recurrent glomerulonephritis after renal
      transplantation. The effect of tacrolimus on nephrotic syndrome after renal
      transplantation is controversial. METHODS: We describe the case of a 30-year-old
      man with steroid-resistant nephrotic syndrome due to FSGS who developed nephrotic
      syndrome 5 years after renal transplantation due to recurrent disease when he was
      switched from cyclosporine to tacrolimus. RESULTS: He was given pulses of
      methylprednisolone and returned to cyclosporine. His proteinuria decreased, but
      he rapidly developed chronic renal failure. CONCLUSIONS: This observation
      strongly suggests that tacrolimus should be given with considerable care in renal
      transplant recipients with FSGS.

PMID- 10071046
TI  - Metalloproteinases and specific inhibitors in multiple sclerosis: from blood to
      brain or vice versa?

PMID- 10071047
TI  - Transthyretin Leu12Pro is associated with systemic, neuropathic and
      leptomeningeal amyloidosis.
AB  - We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro.
      She had extensive amyloid deposition in the leptomeninges and liver as well as
      the involvement of the heart and peripheral nervous system which characterizes
      familial amyloid polyneuropathy caused by variant TTR. Clinical features
      attributed to her leptomeningeal amyloid included radiculopathy, central
      hypoventilation, recurrent subarachnoid haemorrhage, depression, seizures and
      periods of decreased consciousness. MRI showed a marked enhancement throughout
      her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal
      biopsy. The simultaneous presence of extensive visceral amyloid and clinically
      significant deposits affecting both the peripheral and central nervous system
      extends the spectrum of amyloid-related disease associated with TTR mutations.
      The unusual association of severe peripheral neuropathy with symptoms of
      leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be
      considered part of the syndrome of TTR-related familial amyloid polyneuropathy.

PMID- 10071048
TI  - Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A
      longitudinal clinical and MRI study.
AB  - Metalloproteinases have been implicated in the pathogenesis of multiple
      sclerosis. We report longitudinal serum levels of gelatinase B and of the tissue
      inhibitors of matrix metalloproteinases (TIMP), TIMP-1 and TIMP-2, in 21 patients
      with relapsing multiple sclerosis. Patients had monthly clinical and gadolinium
      enhanced MRI follow-up for 10 months. Longitudinal samples in nine healthy
      controls and cross-sectional samples from 12 patients with inflammatory CNS
      disease and 15 patients with other neurological diseases were used for
      comparison. Average serum gelatinase B, TIMP-1 and TIMP-2 levels were
      significantly higher in multiple sclerosis patients and those with other
      neurological diseases than in healthy controls. In the patients with multiple
      sclerosis, gelatinase B levels were significantly higher during clinical relapse
      compared with periods of clinical stability. Multiple sclerosis patients with
      high mean serum gelatinase B levels had significantly more T1-weighted gadolinium
      enhancing MRI lesions than those with mean levels within the control range. TIMP
      1 levels were not different during relapse and between relapses. There was a
      trend for TIMP-2 levels to be lower during relapse compared with non-relapse
      periods. For similar levels of serum gelatinase B, associated TIMP-1 levels were
      significantly lower and TIMP-2 levels significantly higher in multiple sclerosis
      patients compared with the inflammatory CNS control group. We propose that an
      abnormality in the inhibitory response to metalloproteinases may play an
      aetiological role in the chronicity of multiple sclerosis.

PMID- 10071049
TI  - Language processing is strongly left lateralized in both sexes. Evidence from
      functional MRI.
AB  - Functional MRI (fMRI) was used to examine gender effects on brain activation
      during a language comprehension task. A large number of subjects (50 women and 50
      men) was studied to maximize the statistical power to detect subtle differences
      between the sexes. To estimate the specificity of findings related to sex
      differences, parallel analyses were performed on two groups of randomly assigned
      subjects. Men and women showed very similar, strongly left lateralized activation
      patterns. Voxel-wise tests for group differences in overall activation patterns
      demonstrated no significant differences between women and men. In further
      analyses, group differences were examined by region of interest and by
      hemisphere. No differences were found between the sexes in lateralization of
      activity in any region of interest or in intrahemispheric cortical activation
      patterns. These data argue against substantive differences between men and women
      in the large-scale neural organization of language processes.

PMID- 10071050
TI  - Blind smell: brain activation induced by an undetected air-borne chemical.
AB  - EEG and behavioural evidence suggests that air-borne chemicals can affect the
      nervous system without being consciously detected. EEG and behaviour, however, do
      not specify which brain structures are involved in chemical sensing that occurs
      below a threshold of conscious detection. Here we used functional MRI to localize
      brain activation induced by high and low concentrations of the air-borne compound
      oestra-1,3,5(10),16-tetraen-3yl acetate. Following presentations of both
      concentrations, eight of eight subjects reported verbally that they could not
      detect any odour (P = 0.004). Forced choice detection performed during the
      presentations revealed above-chance detection of the high concentration, but no
      better than chance detection of the low concentration compound. Both
      concentrations induced significant brain activation, primarily in the anterior
      medial thalamus and inferior frontal gyrus. Activation in the inferior frontal
      gyrus during the high concentration condition was significantly greater in the
      right than in the left hemisphere (P = 0.03). A trend towards greater thalamic
      activation was observed for the high concentration than the low concentration
      compound (P = 0.08). These findings localize human brain activation that was
      induced by an undetectable air-borne chemical (the low concentration compound).

PMID- 10071051
TI  - Characterization of nodular neuronal heterotopia in children.
AB  - Neuronal heterotopia are seen in various pathologies and are associated with
      intractable epilepsy. We examined brain tissue from four children with
      subcortical or periventricular nodular heterotopia of different aetiologies: one
      with severe epilepsy following focal brain trauma at 17 weeks gestation, one with
      hemimegalencephaly and intractable epilepsy, one with focal cortical dysplasia
      and intractable epilepsy, and one dysmorphic term infant with associated
      hydrocephalus and polymicrogyria. The connectivity of nodules was investigated
      using histological and carbocyanine dye (DiI) tracing techniques. DiI crystal
      placement adjacent to heterotopic nodules revealed numerous DiI-labelled fibres
      within a 2-3 mm radius of the crystals. Although we observed labelled fibres
      closely surrounding nodules, the majority did not penetrate them. Placement of
      DiI crystals within nodules also identified a limited number of projections out
      of the nodules and in one case there was evidence for connectivity between
      adjacent nodules. The cellular and neurochemical composition of nodules was also
      examined using immunohistochemistry for calretinin and neuropeptide Y (NPY),
      which are normally expressed in GABAergic cortical interneurons. Within
      heterotopic nodules from all cases, numerous calretinin-positive neurons were
      identified, along with a few cell bodies and many processes positive for NPY.
      Calretinin-positive neurons within nodules were less morphologically complex than
      those in the cortex, which may reflect incomplete differentiation into an
      inhibitory neuronal phenotype. There were also abnormal clusters of calretinin
      positive cells in the overlying cortical plate, indicating that the migratory
      defect which produces heterotopic nodules also affects development of the cortex
      itself. Thus, heterotopic nodules consisting of multiple neuronal cell types are
      associated with malformation in the overlying cortical plate, and have limited
      connectivity with other brain regions. This abnormal development of connectivity
      may affect neuronal maturation and consequently the balance of excitation and
      inhibition in neuronal circuits, leading to their epileptogenic potential.

PMID- 10071052
TI  - Paradoxical heat sensation in healthy subjects: peripherally conducted by A delta
      or C fibres?
AB  - Paradoxical heat sensation upon cooling of the skin has been reported in central
      as well as in peripheral neurological conditions. In our study, we examined this
      phenomenon in 35 naive healthy test subjects, of whom 23 experienced paradoxical
      heat sensation under test conditions. We measured the peripheral conduction
      velocities of cold sensation, warm sensation and of paradoxical heat sensation by
      using a quantitative sensory testing model of indirect peripheral conduction
      velocity measurement. This was based on comparison of measurements at a proximal
      and a distal site using two measurement methods, one inclusive and the other
      exclusive of reaction time. We found that the conduction velocity of paradoxical
      heat sensation (0.70 m/s) was similar to that of warm sensation (0.68 m/s), and
      that the conduction velocity of cold sensation (7.74-8.01 m/s) was considerably
      faster. Thus, we conclude that paradoxical heat sensation in healthy subjects is
      conducted peripherally via slow unmyelinated C fibres and not via the faster A
      delta fibres. Consequently, we propose that paradoxical heat sensation is encoded
      via the heat sensing pathway, in accordance with the labelled-line code theory.
      The mechanisms proposed suggest a malfunctioning cold-sensing pathway
      disinhibiting the heat-sensing pathway, at peripheral, central or both levels,
      thus facilitating a paradoxical heat sensation.

PMID- 10071053
TI  - Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease.
AB  - Experimental studies indicate that overactivation of the DNA repair protein
      poly(ADP-ribose) polymerase (PARP) in response to oxidative damage to DNA can
      cause cell death due to depletion of NAD+. Oxidative damage to DNA and other
      macromolecules has been reported to be increased in the brains of patients with
      Alzheimer's disease. In the present study we sought evidence of PARP activation
      in Alzheimer's disease by immunostaining sections of frontal and temporal lobe
      from autopsy material of 20 patients and 10 controls, both for PARP itself and
      for its end-product, poly(ADP-ribose). All of the brains had previously been
      subjected to detailed neuropathological examination to confirm the diagnosis of
      Alzheimer's disease or, in the controls, to exclude Alzheimer's disease-type
      pathology. Double immunolabelling for poly(ADP-ribose) and microtubule-associated
      protein 2 (MAP2), glial fibrillary-acidic protein (GFAP), CD68, A beta-protein or
      tau was used to assess the identity of the cells with poly(ADP-ribose)
      accumulation and their relationship to plaques and neurofibrillary tangles. Both
      PARP- and poly(ADP-ribose)-immunolabelled cells were detected in a much higher
      proportion of Alzheimer's disease (20 out of 20) brains than of control brains (5
      out of 10) (P = 0.0018). Double-immunolabelling for poly(ADP-ribose) and markers
      of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68,
      respectively) showed many of the cells containing poly(ADP-ribose) to be neurons.
      Most of these were small pyramidal neurons in cortical laminae 3 and 5. A few of
      the cells containing poly(ADP-ribose) were astrocytes. No poly(ADP-ribose)
      accumulation was detected in microglia. Double-immunolabelling for poly(ADP
      ribose) and tau or A beta-protein indicated that the cells with accumulation of
      poly(ADP-ribose) did not contain tangles and relatively few occurred within
      plaques. Our findings indicate that there is enhanced PARP activity in
      Alzheimer's disease and suggest that pharmacological interventions aimed at
      inhibiting PARP may have a role in slowing the progression of the disease.

PMID- 10071054
TI  - Episodic retrieval activates the precuneus irrespective of the imagery content of
      word pair associates. A PET study.
AB  - The aim of this study was to evaluate further the role of the precuneus in
      episodic memory retrieval. The specific hypothesis addressed was that the
      precuneus is involved in episodic memory retrieval irrespective of the imagery
      content. Two groups of six right-handed normal male volunteers took part in the
      study. Each subject underwent six [15O]butanol-PET scans. In each of the six
      trials, the memory task began with the injection of a bolus of 1500 MBq of
      [15O]butanol. For Group 1, 12 word pair associates were presented visually, for
      Group 2 auditorily. The subjects of each group had to learn and retrieve two sets
      of 12 word pairs each. One set consisted of highly imaginable words and another
      one of abstract words. Words of both sets were not related semantically,
      representing 'hard' associations. The presentations of nonsense words served as
      reference conditions. We demonstrate that the precuneus shows consistent
      activation during episodic memory retrieval. Precuneus activation occurred in
      visual and auditory presentation modalities and for both highly imaginable and
      abstract words. The present study therefore provides further evidence that the
      precuneus has a specific function in episodic memory retrieval as a multimodal
      association area.

PMID- 10071055
TI  - A clinical study of motor evoked potentials using a triple stimulation technique.
AB  - Amplitudes of motor evoked potentials (MEPs) are usually much smaller than those
      of motor responses to maximal peripheral nerve stimulation, and show marked
      variation between normal subjects and from one stimulus to another. Consequently,
      amplitude measurements have low sensitivity to detect central motor conduction
      failures due to the broad range of normal values. Since these characteristics are
      mostly due to varying desynchronization of the descending action potentials,
      causing different degrees of phase cancellation, we applied the recently
      developed triple stimulation technique (TST) to study corticospinal conduction to
      489 abductor digiti minimi muscles of 271 unselected patients referred for
      possible corticospinal dysfunction. The TST allows resynchronization of the MEP,
      and thereby a quantification of the proportion of motor units activated by the
      transcranial stimulus. TST results were compared with those of conventional MEPs.
      In 212 of 489 sides, abnormal TST responses suggested conduction failure of
      various degrees. By contrast, conventional MEPs detected conduction failures in
      only 77 of 489 sides. The TST was therefore 2.75 times more sensitive than
      conventional MEPs in disclosing corticospinal conduction failures. When the
      results of the TST and conventional MEPs were combined, 225 sides were abnormal:
      145 sides showed central conduction failure, 13 sides central conduction slowing
      and 67 sides both conduction failure and slowing. It is concluded that the TST is
      a valuable addition to the study of MEPs, since it improves detection and gives
      quantitative information on central conduction failure, an abnormality which
      appears to be much more frequent than conduction slowing. This new technique will
      be useful in following the natural course and the benefit of treatments in
      disorders affecting central motor conduction.

PMID- 10071056
TI  - The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is
      associated with a clinically distinct Charcot-Marie-Tooth phenotype.
AB  - We observed a missense mutation in the peripheral myelin protein zero gene (MPZ,
      Thr124Met) in seven Charcot-Marie-Tooth (CMT) families and in two isolated CMT
      patients of Belgian ancestry. Allele-sharing analysis of markers flanking the MPZ
      gene indicated that all patients with the Thr124Met mutation have one common
      ancestor. The mutation is associated with a clinically distinct phenotype
      characterized by late onset, marked sensory abnormalities and, in some families,
      deafness and pupillary abnormalities. Nerve conduction velocities of the motor
      median nerve vary from <38 m/s to normal values in these patients. Clusters of
      remyelinating axons in a sural nerve biopsy demonstrate an axonal involvement,
      with axonal regeneration. Phenotype-genotype correlations in 30 patients with the
      Thr124Met MPZ mutation indicate that, based on nerve conduction velocity
      criteria, these patients are difficult to classify as CMT1 or CMT2. We therefore
      conclude that CMT patients with slightly reduced or nearly normal nerve
      conduction velocity should be screened for MPZ mutations, particularly when
      additional clinical features such as marked sensory disturbances, pupillary
      abnormalities or deafness are also present.

PMID- 10071057
TI  - Infratentorial atrophy on magnetic resonance imaging and disability in multiple
      sclerosis.
AB  - Loss of tissue volume in the central nervous system may provide an index of fixed
      neurological dysfunction in multiple sclerosis. Recent magnetic resonance studies
      have shown a modest relationship between clinical disability rating scores and
      transverse sectional area of the cervical spinal cord. To explore further the
      relationship between atrophy and disability in multiple sclerosis, we estimated
      the volumes of infratentorial structures from MRIs in a cross-sectional study of
      41 patients, 21 with relapsing-remitting multiple sclerosis and 20 with secondary
      progressive multiple sclerosis. We used the Cavalieri method of modern design
      stereology with point counting to estimate the volume of brainstem, cerebellum
      and upper cervical spinal cord from three-dimensional MRIs acquired with an
      MPRAGE (Magnetization-prepared Rapid Acquisition Gradient Echo) sequence. The
      volume of the upper (C1-C3) cervical spinal cord was significantly correlated
      with a composite spinal cord score derived from the appropriate Functional Scale
      scores of the Expanded Disability Status Scale (r = -0.50, P < 0.01). The
      cerebellar (r = 0.49, P < 0.01) and brainstem (r = 0.34, P < 0.05) volumes
      correlated with the Scripp's Neurological Disability Rating Scale scores. The
      upper cervical cord volumes (r = -0.39, P < 0.01), but not the brainstem or
      cerebellar volumes, were significantly associated with disease duration. MRI
      estimated structural volumes may provide a simple index of axonal and/or myelin
      loss, the presumed pathological substrates of irreversible impairment and
      disability in multiple sclerosis.

PMID- 10071058
TI  - Impairment in preattentive visual processing in patients with Parkinson's
      disease.
AB  - We explored the possibility of whether preattentive visual processing is impaired
      in Parkinson's disease. With this aim, visual discrimination thresholds for
      orientation texture stimuli were determined in two separate measurement sessions
      in 16 patients with idiopathic Parkinson's disease. The results were compared
      with those of 16 control subjects age-matched and 16 young healthy volunteers.
      Discrimination thresholds were measured in a four-alternative spatial forced
      choice paradigm, in which subjects judged the location of a target embedded in a
      background of distractors. Four different stimulus configurations were employed:
      (i) a group of vertical targets among horizontal distractors ('vertical line
      targets'); (ii) targets with varying levels of orientation difference on a
      background of spatially filtered vertically oriented noise ('Gaussian filtered
      noise'); (iii) one 'L' among 43 '+' signs ('texton'), all of which assess
      preattentive visual processing; and (iv) control condition, of one 'L' among 43
      'T' distractors ('non-texton' search target), which reflects attentive visual
      processing. In two of the preattentive tasks (filtered noise and texton),
      patients with Parkinson's disease required significantly greater orientation
      differences and longer stimulus durations, respectively. In contrast, their
      performance in the vertical line target and non-texton search target was
      comparable to that of the matched control subjects. These differences were more
      pronounced in the first compared with the second session. Duration of illness and
      age within the patient group correlated significantly with test performance. In
      all conditions tested, the young control subjects performed significantly better
      than the more elderly control group, further indicating an effect of age on this
      form of visual processing. The results suggest that, in addition to the well
      documented impairment in retinal processing, idiopathic Parkinson's disease is
      associated with a deficit in preattentive cortical visual processing.

PMID- 10071059
TI  - The effects of posteroventral pallidotomy on the preparation and execution of
      voluntary hand and arm movements in Parkinson's disease.
AB  - We studied the effect of posteroventral pallidotomy on movement preparation and
      execution in 27 parkinsonian patients using various motor tasks. Patients were
      evaluated after overnight withdrawal of medication before and 3 months after
      unilateral pallidotomy. Surgery had no effect on initiation time in unwarned
      simple and choice reaction time tasks, whereas movement time measured during the
      same tasks was improved for the contralesional hand. Movement times also improved
      for isometric and isotonic ballistic movements. In contrast, repetitive, distal
      and fine movements measured in finger-tapping and pegboard tasks were not
      improved after pallidotomy. Preparatory processes were investigated using both
      behavioural and electrophysiological measures. A precued choice reaction time
      task suggested an enhancement of motor preparation for the contralesional hand.
      Similarly, movement-related cortical potentials showed an increase in the slope
      of the late component (NS2) when the patients performed joystick movements with
      the contralesional hand. However, no significant change was found for the early
      component (NS1) or when the patient moved the ipsilesional hand. The amplitude of
      the long-latency stretch reflex of the contralesional hand decreased after
      surgery. In summary, the data suggest that pallidotomy improved mainly the later
      stages of movement preparation and the execution of proximal movements with the
      contralesional limb. These results provide detailed quantitative data on the
      impact of posteroventral pallidotomy on previously described measures of upper
      limb akinesia in Parkinson's disease.

PMID- 10071060
TI  - Brain activation during maintenance of standing postures in humans.
AB  - The regulatory mechanism of bipedal standing in humans remains to be elucidated.
      We investigated neural substrates for maintaining standing postures in humans
      using PET with our mobile gantry PET system. Normal volunteers were instructed to
      adopt several postures: supine with eyes open toward a target; standing with feet
      together and eyes open or eyes closed; and standing on one foot or with two feet
      in a tandem relationship with eyes open toward the target. Compared with the
      supine posture, standing with feet together activated the cerebellar anterior
      lobe and the right visual cortex (Brodmann area 18/19), and standing on one foot
      increased cerebral blood flow in the cerebellar anterior vermis and the posterior
      lobe lateral cortex ipsilateral to the weight-bearing side. Standing in tandem
      was accompanied by activation within the visual association cortex, the anterior
      and posterior vermis as well as within the midbrain. Standing with eyes closed
      activated the prefrontal cortex (Brodmann area 8/9). Our findings confirmed that
      the cerebellar vermis efferent system plays an important role in maintenance of
      standing posture and suggested that the visual association cortex may subserve
      regulating postural equilibrium while standing.

PMID- 10071061
TI  - Selective horizontal dysmetropsia following prestriate lesion.
AB  - We describe a patient (P.S.) who, following a right prestriate lesion, reported
      that objects in the left visual field appeared distorted and smaller than those
      on the right. Other aspects of visual processing were remarkably unaffected. We
      carried out a series of size comparison tests using simple or complex stimuli and
      requiring different types of behavioural responses. We found that P.S.
      significantly underestimated the size of stimuli presented in her left visual
      field. When comparison tasks involved stimuli placed along the vertical axis or
      in the right visual field, P.S. performed well. The vertical and horizontal
      components of size distortion were found to be differentially affected. We
      conclude that size processing may be dissociated from other aspects of visual
      processing, such as form or colour processing, and depends critically on part of
      the occipital, prestriate areas (Brodmann areas 18-19).

PMID- 10071062
TI  - The role of ventral medial wall motor areas in bimanual co-ordination. A combined
      lesion and activation study.
AB  - Two patients with midline tumours and disturbances of bimanual co-ordination as
      the presenting symptoms were examined. Both reported difficulties whenever the
      two hands had to act together simultaneously, whereas they had no problems with
      unimanual dexterity or the use of both hands sequentially. In the first patient
      the lesion was confined to the cingulate gyrus; in the second it also invaded the
      corpus callosum and the supplementary motor area. Kinematic analysis of bimanual
      in-phase and anti-phase movements revealed an impairment of both the temporal
      adjustment between the hands and the independence of movements between the two
      hands. A functional imaging study in six volunteers, who performed the same
      bimanual in-phase and anti-phase tasks, showed strong activations of midline
      areas including the cingulate and ventral supplementary motor area. The prominent
      activation of the ventral medial wall motor areas in the volunteers in
      conjunction with the bimanual co-ordination disorder in the two patients with
      lesions compromising their function is evidence for their pivotal role in
      bimanual co-ordination.

PMID- 10071063
TI  - Development of specific synaptic network functions in organotypic central nervous
      system (CNS) cultures: implications for transplantation of CNS neural cells in
      vivo.
AB  - This article provides a broad overview of the significant roles that
      morphophysiologic analyses of organotypic cultures of neural tissues explanted in
      vitro-initiated during the 1950s-have played in stimulating the more recent
      development of techniques for transplantation of neural cells and tissues into
      specific regions of the central nervous system (CNS) in vivo. The demonstrations
      by Crain and co-workers in the 1950s and 1960s that fetal rodent and human CNS
      neurons can continue to develop a remarkable degree of mature structure and
      function during many months of complete isolation in culture provided crucial
      evidence that development of many organotypic properties of nerve cells is
      regulated by epigenetic factors that ensure rather stereotyped expression despite
      wide variations in environmental conditions. These in vitro studies strongly
      suggested that fetal neural cells should, indeed, be capable of even more highly
      organotypic development after transplantation in vivo, as has been elegantly
      demonstrated by many of the successful CNS transplantation studies reviewed here.

PMID- 10071064
TI  - Buoyant density gradient fractionation and flow cytometric analysis of embryonic
      rat cortical neurons and progenitor cells.
AB  - We have used the property of natural cell buoyant density to selectively
      fractionate embryonic rat neocortical cells into 20 subpopulations ranging in
      phenotype from proliferatively active progenitors to terminally postmitotic
      neurons. Immunocytochemical and cell cycle analysis of the cellular fractions
      with flow cytometry revealed an inverse relationship between cell buoyant density
      and neuronal differentiation. The most buoyant fractions contained predominantly
      terminally postmitotic, tubulin betaIII-positive, tetanus toxin-positive, and
      nestin-negative differentiating neurons, while immature, bromodeoxyuridine
      positive and nestin-positive proliferating cells were more prevalent in less
      buoyant fractions. Double loading of isolated cells with voltage- and Ca2+
      sensitive fluorescent indicator dyes followed by simultaneous recordings of
      membrane potential and cytoplasmic [Ca2+] ([Ca2+]c]) using flow cytometry
      revealed that >50% of the least buoyant cells produced functional responses to
      veratridine, a Na+ channel agonist, and muscimol, a GABA(A) receptor agonist, but
      <10% responded to kainic acid, an agonist of a subset of glutamate receptors. As
      cells became more buoyant the percentage of cells that depolarized and produced a
      rise in [Ca2+]c to each ligand increased, particularly in response to kainic
      acid. Short-term culture of select fractions revealed a marked enrichment for
      cells with morphologies and epitopes characteristic of neuronal and progenitor
      cell subpopulations. The results show that embryonic cortical cells exhibit a
      range of naturally occurring buoyant densities that can be used to expeditiously
      fractionate cortical cells according to their pre- or postmitotic status, thus
      providing ready access for cellular and molecular studies of proliferation and
      differentiation.

PMID- 10071065
TI  - Purification of human fetal hippocampal neurons by flow cytometry for
      transplantation.
AB  - We have established primary cultures, highly enriched in neurons, from the
      hippocampus of human fetal brains at 20-23 gestational weeks. More than 80% of
      cells were viable when seeded. Neurons were isolated from primary cultures by
      flow cytometry to a high degree of purity, as demonstrated by immunocytochemical
      staining. FACS scanning analysis using a DNA-staining dye showed that hippocampal
      neurons did not divide in culture. To demonstrate that FACS-sorted neurons can be
      transplanted and integrated into the host brain, neuron-enriched primary culture
      from human fetal striatum was infected with a viral-mediated vector containing a
      reporter gene, beta-galactosidase. Striatal neurons were subsequently purified by
      flow cytometry and transplanted into the striatum of rats. Following
      transplantation, the rat brains were processed for beta-galactosidase
      histochemistry and electron microscopy. Beta-galactosidase expression indicates
      that transplanted human neurons survived in the host and were metabolically
      active. The transplanted neurons received synaptic inputs, as judged from the
      presence of presynaptic terminals on their surface. Our study demonstrates
      connectivity between transplanted human fetal primary neurons and host tissue at
      the ultrastructural level. Our results support the feasibility of ultimately
      transplanting neurons into humans as a possible treatment for recovery of the
      nervous system (e.g., neurodegenerative diseases).

PMID- 10071066
TI  - The neuronal progenitor cells of the forebrain subventricular zone: intrinsic
      properties in vitro and following transplantation.
AB  - During the development of the central nervous system, progenitor cells, located
      within distinct germinal zones, produce presumptive neurons that migrate to their
      destinations and differentiate. Recent studies have demonstrated that a discrete
      region of the anterior part of the postnatal subventricular zone (SVZa) comprises
      neuronal progenitor cells whose progeny are fated to become the interneurons of
      the olfactory bulb. The SVZa is of particular interest because it is one of few
      germinal zones to persist postnatally and may be the only postnatal germinal zone
      to give rise exclusively to neurons. To the extent that the SVZa is unique among
      proliferative zones, the SVZa progeny are unique among neurons. First, unlike
      most cortical neurons, the SVZa-derived cells do not rely on radial glia-assisted
      migration when traveling to their target region. Second, the SVZa progeny
      continue to proliferate as they migrate to their target region. And third, the
      SVZa progeny express early neuron-specific antigens prior to their final division
      and, therefore, prior to reaching their destination where they will terminally
      differentiate. To better understand the capacity of the SVZa progeny to
      concurrently proliferate, migrate, and differentiate, we studied the cells in
      vitro and following transplantation into the neonatal SVZa and adult striatum. In
      each setting, we found that the SVZa cells continue both to proliferate and to
      differentiate into neurons. In addition, after homotopic and heterotopic
      transplantation, we found that the SVZa cells maintain their ability to migrate.
      These results suggest that the unique features of the SVZa progeny are specified
      intrinsically rather than by their extrinsic environment.

PMID- 10071067
TI  - Isolation and characterization of immature oligodendrocyte lineage cells.
AB  - Using in vitro systems, the proliferation, migration, differentiation, and
      survival of immature oligodendrocyte lineage cells can be examined to elucidate
      the cellular and molecular interactions that regulate this lineage. The ability
      to monitor progressive stages of differentiation within the lineage by
      immunophenotyping and to manipulate the cellular responses with growth factors
      makes these cultures advantageous as both a method for studying the cell biology
      of myelination and as a model system for lineage analysis in the mammalian
      central nervous system. In addition, cultured oligodendrocytes carry out the
      normal in vivo sequence of expression of a set of cell type-specific genes, some
      of which are extremely highly expressed, and so provide advantages for analysis
      of gene regulation. This paper describes commonly used methods for the
      preparation of mixed glial cell cultures from perinatal rodent brain. Although
      these cultures are most commonly derived from perinatal rat brain, a protocol for
      preparation from mouse brain is also provided because of the increasing number of
      studies that use mice to facilitate molecular biological techniques. Methods to
      prepare secondary cultures of different stages of oligodendrocyte lineage cells
      are detailed. As examples of methods to use for the characterization of these
      cells, immunophenotypes of each stage of the oligodendrocyte lineage are
      illustrated, incorporation of [3H]thymidine for analysis of cell proliferation is
      illustrated, and detailed methods are provided for analysis of migration in a
      microchemotaxis chamber.

PMID- 10071068
TI  - Functional studies in cultured astrocytes.
AB  - Studies using primary cultures of astrocytes have made essential contributions to
      the understanding of astrocytic functions and neuronal-astrocytic interactions.
      The purposes of this article are to (i) outline principles and methodologies used
      in the preparation of such cultures and caveats for the interpretation of the
      observations made; (ii) summarize astrocytic functions in turnover of the amino
      acid transmitters glutamate and gamma-aminobutyric acid (GABA), in energy
      metabolism and in Na+,K+-ATPase-catalyzed processes and emphasize the degree to
      which the observations have been confirmed in intact tissue; (iii) describe
      regulations of astrocytic functions by transmitters and by calcium channel
      activity; and (iv) indicate suggestions for future functional studies using
      astrocytes in primary cultures and emphasize that some of the conclusions about
      neuronal-astrocytic interactions reached on the basis of studies in cultured
      cells and confirmed in intact tissue may not yet have been completely integrated
      into general neuroscience knowledge.

PMID- 10071069
TI  - Transplanting myelin-forming cells into the central nervous system: principles
      and practice.
AB  - Although transplantation of myelin-forming cells into the central nervous system
      (CNS) has recently attracted much attention as a potential therapy for repairing
      persistent demyelination found in the demyelinating diseases such as multiple
      sclerosis and the leukodystrophies, it is worth remembering that the technique
      was originally conceived of as an experimental technique for manipulating in vivo
      environments to study interactions between different cell types in either repair
      or development. It is in this capacity that the technique is still predominantly
      used. Nevertheless, information, both technical and biological, that the
      continued use of the technique yields also often provides material for assessing
      the feasibility of glial cell transplantation as a therapeutic procedure. In this
      article, we describe some of the guiding principles of transplantation of
      myelinogenic cells into the mammalian CNS, focusing initially on the recipient
      environment and then considering the donor material. The division of the
      discussion into recipient and donor is one of convenience since in reality the
      interactions between the two cannot be considered in isolation.

PMID- 10071070
TI  - Microglia in cell culture and in transplantation therapy for central nervous
      system disease.
AB  - The central nervous system (CNS) is host to a significant population of
      macrophage-like cells known as microglia. In addition to these cells which reside
      within the parenchyma, a diverse array of macrophages are present in meningeal,
      perivascular, and other peripheral locations. The role that microglia and other
      CNS macrophages play in disease and injury is under intensive investigation, and
      functions in development and in the normal adult are just beginning to be
      explored. At present the biology of these cells represents one of the most
      fertile areas of CNS research. This article describes methodology for the
      isolation and maintenance of microglia in cell cultures prepared from murine and
      feline animals. Various approaches to identify microglia are provided, using
      antibody, lectin, or scavenger receptor ligand. Assays to confirm macrophage-like
      functional activity, including phagocytosis, lysosomal enzyme activity, and
      motility, are described. Findings regarding the origin and development of
      microglia and results of transplantation studies are reviewed. Based on these
      data, a strategy is presented that proposes to use the microglial cell lineage to
      effectively deliver therapeutic compounds to the CNS from the peripheral
      circulation.

PMID- 10071071
TI  - Generation and regulation of developing immortalized neural cell lines.
AB  - The genetic and environmental signals that regulate progressive lineage
      elaboration in the mammalian brain are poorly understood. In addition,
      characterization of the developmental profiles of early central nervous system
      (CNS) stem/ progenitor cells and analysis of the mechanisms involved in their
      clonal expansion, lineage restriction, and cellular maturation have been
      fragmentary and elusive. These seminal neurodevelopmental issues have been
      examined using a series of clonally derived neural stem/progenitor cell lines
      established by retroviral transduction of embryonic (E16.5-E17.5) murine
      hippocampal and cerebellar cells using temperature-sensitive alleles (A58/U19) of
      the simian virus (SV) 40 large tumor (T) antigen. Under conditions permissive for
      T-antigen expression (33 degrees C), single neural stem cells exhibited self
      renewal, clonal expansion, and both symmetric and asymmetric modes of cell
      division. By contrast, at the nonpermissive temperature for T-antigen expression
      (39 degrees C), specific sets of cytokines potentiated the progressive
      elaboration of neuronal, oligodendroglial, and astroglial lineage species. These
      observations demonstrate that a spectrum of genetic and epigenetic signals and
      distinct cellular processes are involved in orchestrating the evolution of
      individual neural lineages from regional CNS stem/progenitor species. Further,
      the availability of conditionally immortalized neural cell lines that can be
      transplanted back into the mammalian brain may represent an important
      experimental resource for the detailed characterization of cellular and molecular
      mechanisms involved in the developmental sculpting, plasticity, and regeneration
      of the mammalian CNS.

PMID- 10071072
TI  - Leukemia cell lines: in vitro models for the study of Philadelphia chromosome
      positive leukemia.
AB  - The Philadelphia (Ph) chromosome, the main product of the (9;22)(q34;q11)
      translocation, is the cytogenetic hallmark of chronic myeloid leukemia (CML), a
      clonal myeloproliferative disorder of the hematopoietic stem cell; the Ph
      chromosome is also found in a sizeable portion of acute lymphoblastic leukemia
      (ALL) patients and in a small number of acute myeloid leukemia (AML) cases. At
      the molecular level, the t(9;22) leads to the fusion of the BCR gene (on
      chromosome 22) to the ABL gene (translocated from chromosome 9); this fusion gene
      BCR-ABL with its elevated tyrosine kinase activity must to be central to the
      pathogenesis of these disorders. Three different breakpoint cluster regions are
      discerned within the BCR gene on chromosome 22: M-bcr, m-bcr, and mu-bcr. Ph +
      leukemia cell lines are important tools in this research area. More than 20 ALL
      and more than 40 CML-derived Ph + leukemia cell lines have been described.
      Furthermore, three Ph + B-lymphoblastoid cell lines, established from patients
      with Ph + ALL or CML, are available. Molecular analysis has documented BCR-ABL
      fusion genes in three apparently Ph chromosome-negative cell lines, all three
      derived from CML. Nearly all Ph + ALL cell lines have the m-bcr e1-a2 fusion gene
      (only two ALL cell lines have a b3-a2 fusion) whereas all CML cell lines, but one
      carry the M-bcr b2-a2, b3-a2 or both hybrids. The mu-bcr e19-a2 has been detected
      in one CML cell line. Four cell lines display a three-way translocation involving
      chromosomes 9, 22 and a third chromosome. Additional Ph chromosomes (up to five)
      have been found in four Ph + ALL cell lines and in 18 CML cell lines; though in
      some cell lines the extra Ph chromosome(s) might be caused by the polyploidy (tri
      and tetraploidy) of the cells. Another modus to acquire additional copies of the
      BCR-ABL fusion gene is the formation of tandem repeats of the BCR-ABL hybrid as
      seen in CML cell line K-562. Both mechanisms, selective multiplication of the
      der(22) chromosome and tandem replication of the fusion gene BCR-ABL, presumably
      lead to enhanced levels of the fusion protein and its tyrosine kinase activity
      (genetic dosage effect). The availability of a panel of Ph + cell lines as highly
      informative leukemia models offers the unique opportunity to analyze the
      pathobiology of these malignancies and the role of the Ph chromosome in
      leukemogenesis.

PMID- 10071073
TI  - The effect of sclareol on growth and cell cycle progression of human leukemic
      cell lines.
AB  - Sclareol, a labdane-type diterpene, was tested for cytotoxic effect against a
      panel of established human leukemic cell lines. The compound showed an IC50 lower
      than 20 microg/ml in most cell lines tested, while it was higher for resting
      peripheral blood mononuclear leukocytes (PBML). Furthermore, the compound was
      tested for cytostatic activity against four of the leukemic cell lines used. At a
      concentration of 20 microg/ml the compound showed a significant cytostatic effect
      as soon as 4 h after continuous incubation against two from B and two from T
      lineage cell lines. The morphology and the kind of death induced from sclareol in
      three cell lines, was also investigated. The effect of sclareol on the cell cycle
      progression of two cell lines, using flow cytometry, was examined. The results
      show that sclareol kills cell lines, through the process of apoptosis. The
      appearance of the apoptotic signs is time and dose dependent. From the flow
      cytometry experiments, a delay of the cell population on G0/1 seems to take
      place. This is the first report, that a labdane type diterpene kills tumor cells
      via a phase specific mechanism which induces apoptosis.

PMID- 10071074
TI  - Molecular mechanism involved in TPA-induced myelopoietic programming.
AB  - The study, addressed to understand the mechanism responsible for 12-O
      tetradecanoyl phorbol-13-acetate (TPA)-induced myeloid differentiation, revealed
      that the inherent capacity of TPA to induce expression of Receptor-C(K) in HL-60
      cells (which are unable to express Receptor-C(K) in their native state) is
      responsible for its ability to induce phenotypic differentiation of HL-60 cells.
      Based upon these results, we propose that Receptor-C(K) dependent signalling is
      the Critical 'Molecular Switch' responsible for TPA-induced myelopoietic
      programming.

PMID- 10071075
TI  - Bone marrow stroma from refractory anemia of myelodysplastic syndrome is
      defective in its ability to support normal CD34-positive cell proliferation and
      differentiation in vitro.
AB  - We examined the supportive function of stromal cells from patients with
      refractory anemia (RA) of myelodysplastic syndrome (MDS) on CD34-positive
      hematopoietic cell proliferation and differentiation using a long-term bone
      marrow culture (LTMC) system. Primary marrow stromal cells were obtained from 11
      MDS RA patients and 12 healthy volunteers, and freshly prepared CD34-positive
      bone marrow cells from a normal subject were inoculated onto the stroma. There
      seems to be three broad patterns of hematopoietic cell growth in the LTMCs. In
      one group, hematopoietic cells were maintained at near normal levels (type A). In
      the second group, the number of hematopoietic cells increased within the first 5
      10 days of culture, but declined to low levels at 15-20 days of culture as
      compared with normal control (type B). In the third group, the incidence of
      hematopoietic cells steadily declined from the beginning of the culture (type C).
      Furthermore, apoptotic change of hematopoietic cells was very frequently observed
      in cultures with the type C stroma, which were especially defective for
      supporting CD34 + cell proliferation and differentiation. The expression of CD95
      on hematopoietic cells was induced by the type C stroma, however, production of
      fas ligand by the stromal cells was not observed. These findings suggest a lack
      of hematopoietic supportive function in some cases of MDS RA and also indicate
      that there is heterogeneity of stromal function among MDS RA patients.

PMID- 10071076
TI  - Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with
      chronic myeloid leukemia in acute megakaryoblastic blast crisis.
AB  - Human p55, the major palmitoylated protein associated with the cytoplasmic face
      of the erythrocyte membrane, is believed to modulate interactions between protein
      4.1 and glycophorin C. It is the prototype of a newly described family of
      signaling molecules that includes hD1g, the human homologue of the Drosophila
      discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized
      by transformation to a fulminating acute leukemia, heralded by evolution of the
      Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR
      of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base
      pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The
      deletion of constitutive exon 5 not only marks the first abnormality of the p55
      cDNA in human disease but also the first abnormality of a PDZ domain in human
      disease and may represent another genetic abnormality associated with CML in
      blast crisis.

PMID- 10071077
TI  - Methylation status of the 3rd exon of the c-MYC oncogene in B-cell malignancies.
AB  - We examined the methylation status of the third exon of the MYC oncogene in 39
      patients with B-cell malignancies. DNA was digested with MspI plus EcoRI or HpaII
      plus EcoRI and hybridised with a probe specific for the third exon of MYC. Thirty
      four patients showed complete methylation of the CCGG site. Four patients, one
      with chronic B-cell leukaemia and one with pro-lymphocytic leukaemia (PLL) and
      two with B-cell lymphoma showed partial hypomethylation of the CCGG site, while
      another patient with PLL showed complete hypomethylation of the CCGG site. These
      results suggest that hypomethylation of the MYC oncogene is infrequent in B-cell
      tumours but may be involved in the development of some cases of B-cell
      malignancies.

PMID- 10071078
TI  - Establishment of a double Philadelphia chromosome-positive acute lymphoblastic
      leukemia-derived cell line, TMD5: effects of cytokines and differentiation
      inducers on growth of the cells.
AB  - A double Philadelphia chromosome (Ph)-positive leukemia cell line with common-B
      cell phenotype, designated TMD5, was established from the blast cells of a
      patient with double Ph-positive acute lymphoblastic leukemia. TMD5 cells
      expressed 190 kDa BCR/ABL chimeric protein and 145 kDa ABL protein. The cells
      proliferated without added growth factors. Autocrine growth mechanism was not
      recognized. The addition of growth factors such as G-CSF, GM-CSF, IL-3, IL-6, or
      Stem Cell Factor did not affect the growth. Herbimycin A suppressed the growth of
      TMD5 cells at the low concentration that did not affect Ph-negative cells. It
      suppressed tyrosine phosphorylation of intracellular proteins in TMD5 cells.
      Dexamethasone and dibutyryl cyclic AMP also suppressed the growth. They, however,
      did not affect the phosphorylation significantly. Neither all-trans retinoic acid
      nor interferon-alpha affected the growth. TMD5 cells, characterized minutely here
      and rare in that they have double Ph chromosomes, will be a useful tool for the
      study of Ph-positive leukemia.

PMID- 10071079
TI  - Acridones as inducers of HL-60 cell differentiation.
AB  - Fifteen acridone alkaloids were examined for their activity of induction of human
      promyelocytic leukemia cell (HL-60) differentiation. HL-60 cells were
      differentiated into mature monocyte/macrophage by atalaphyllidine (9),
      atalaphyllinine (12), and des-N-methylnoracronycine (13). The activities of NBT
      reduction, nonspecific esterase, and phagocytosis, were induced by 2.5 microM of
      9, 12, and 13. After a 4-day treatment, 9, 12, and 13 at 10 microM inhibited
      clonal proliferation of HL-60 cells by 28, 96, and 63%, respectively. The
      structure-activity relationship established from the results revealed that
      hydroxyl group at C-1 and prenyl group at C-2 had an important role.

PMID- 10071080
TI  - Low plasma stem cell factor levels correlate with in vitro leukemic growth in
      myelodysplastic syndromes.
AB  - We evaluated the effect of SCF on myeloid differentiation by correlating
      clonogenic potential (as CFU-GM), bone marrow (BM) plasma SCF levels and CD34/c
      kit expression in 57 MDS samples. There was a significant correlation between low
      SCF levels and 'leukemic' in vitro growth, the number of clusters and the
      colony/cluster ratio. No correlation was found between BM plasma SCF levels, the
      pattern of growth and CD34+ c-kit+ expression. These data seem to exclude any
      direct effect of SCF on leukemogenesis, but suggest that low plasma SCF levels
      may be at least partially responsible for leukemic growth in MDS.

PMID- 10071081
TI  - Chemosensitivity in vitro to 2-chlorodeoxyadenosine and 9-beta-D-arabinofuranosyl
      2-fluoroadenine in previously unexposed cases of chronic lymphocytic leukemia.
AB  - The chemosensitivity of leukemia cells, obtained from the peripheral blood of 35
      patients with B-cell chronic lymphocytic leukemia, was determined by a leucine
      incorporation assay in vitro. There was good correlation between the
      sensitivities to two purine analogs, 2-chlorodeoxyadenosine and 9-beta-D
      arabinofuranosyl-2-fluoroadenine among previously untreated patients when tested
      at the 80% inhibition level. Previous exposure to chlorambucil did not affect the
      sensitivity to these compounds.

PMID- 10071082
TI  - The risk of secondary leukemias following autologous stem cell transplantation.

PMID- 10071083
TI  - Myelodysplastic syndrome: a search for minimal diagnostic criteria.
AB  - We have evaluated dyshemopoietic features in bone marrow (BM) samples obtained
      from healthy people aged over 50 without peripheral blood (PB) cytopenia patients
      and compared them with MDS patients. Control group displayed BM features of
      dyserythropoiesis and dysgranulopoiesis in up to 15 and 27% of the considered
      cell elements (P90) respectively, overlapping in part with MDS patients.
      Interobserver agreement in dyshemopoietic features was highest for BM blast cell
      and pathological sideroblast counts. An algorithm based on BM blast cell and
      pathological sideroblast counts that has been verified on 613 patients from
      different Spanish centers may be of help to improve reproducibility in
      Myelodysplastic syndrome (MDS) diagnosis.

PMID- 10071084
TI  - Cytogenetic and myelodysplastic alterations after autologous hemopoietic stem
      cell transplantation.
AB  - Secondary myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) are today
      considered a primary complication of autologous hematopoietic stem cell
      transplantation. In our Center, 83 autografted patients underwent bone marrow
      (BM) biopsy and cytogenetic analysis at fixed intervals. Twelve patients
      developed non-clonal cytogenetic abnormalities and 10 patients clonal
      abnormalities, five of whom (three - 7, one - 5 and one t(9;11)) developed
      secondary MDS/AML. MDS was also diagnosed in two patients with a normal
      karyotype. In brief, seven patients (three males, four females; median age 36
      years) developed MDS/AML 12-48 months (median 14) after autografting. The FAB
      diagnosis was AML-M2 in one, chronic myelomonocytic leukemia in two and
      refractory anemia with excess of blasts in transformation in four cases. Two
      patients presented a BM biopsy picture of MDS with fibrosis; none of them
      experienced leukemic transformation. Four MDS patients died, three of leukemic
      transformation and one of BM insufficiency; the two remaining patients are still
      living and untransformed. Our data underline the leukemogenic role of previous
      treatments, even if it is not possible to exclude that underlying disease and/or
      conditioning therapy may be involved.

PMID- 10071085
TI  - Polycythemia vera megakaryocytes store and release lysozyme to a higher extent
      than megakaryocytes in secondary polycythemia (polyglobuly).
AB  - Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also
      immunomodulatoric properties and was found to bind to the glycosaminoglycan
      serglycin, an important constituent of the extracellular matrix (ECM).
      Pathological serum lysozyme levels were described in chronic myeloproliferative
      disorders (CMPDs) and other hematological conditions. In this context it is
      remarkable that in polycythemia rubra vera (PV), characterized by a proliferation
      particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave
      independently of the numbers of myelomonocytic cells in peripheral blood. To
      elucidate whether megakaryopoiesis might be the source of the increased serum
      lysozyme, we performed an experimental study on isolated and enriched
      megakaryocytes derived from bone marrow of patients with PV. Findings were
      compared to a group of patients with reactive (smoker's) polyglobuly (PG). In
      confirmation of previous results, quantification of serum lysozyme levels showed
      a slight elevation in the cohort of PV patients which was not correlated with the
      leukocyte count. Applying an immunohistochemical assay we were able to
      demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover,
      performing the reverse hemolytic plaque assay (RHPA), a technique which enables
      detection of secreted proteins at the single cell level, we found that 54% of the
      PV, but only 3% of the PG megakaryocytes spontaneously secreted lysozyme. After
      rhIL-3 treatment the secretion of lysozyme remained unchanged in PV but increased
      to 14% in PG. These findings suggest that the extent of megakaryocytic lysozyme
      secretion might discriminate PV from reactive conditions. Although a direct
      involvement of lysozyme in the regulation of aberrant megakaryopoiesis in PV is
      not likely, the results of the present study point to the possibility that
      lysozyme could be involved in the interactions of PV megakaryocytes with ECM.
      Moreover, the response to rhIL-3 significantly discriminates PV megakaryocytes
      from megakaryocytes of the PG group.

PMID- 10071086
TI  - Allelotyping of acute myelogenous leukemia: loss of heterozygosity at 7q31.1
      (D7S486) and q33-34 (D7S498, D7S505).
AB  - Loss of a whole chromosome 7(-7) or a deletion of the long arm of chromosome 7
      del(7q) occurs frequently in many types of primary cancers including cases of
      acute myelogenous leukemia (AML). We analyzed for loss of heterozygosity (LOH) of
      chromosome arm 7q in 26 AML cases using a set of 15 microsatellite markers in
      order to begin to determine the location of putative tumor suppressor genes (TSG)
      important to this disease. Seven samples (27%) showed LOH at one or more loci on
      chromosome 7q. We identified the smallest commonly deleted regions to be at
      7q31.1 (D7S486) and 7q33-34 (D7S498, D7S505) suggesting that alterations of a TSG
      in each region have an important role in de novo AML.

PMID- 10071087
TI  - Correlation of telomerase activity with development and progression of adult T
      cell leukemia.
AB  - Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats to the ends
      of vertebrate chromosomal DNAs (i.e. telomeres) to compensate for losses that
      occur with each round of DNA replication. Telomerase activity, demonstrable in
      most human tumors, enables them to maintain telomere stability. Peripheral blood
      mononuclear cells were sampled from 57 patients seropositive for human T
      lymphotropic virus type I (HTLV-I), including 24 asymptomatic viral carriers, ten
      smoldering type, five chronic type, and 18 acute type adult T-cell leukemia
      (ATL). Telomerase activity was determined in samples using a modified telomeric
      repeat amplification protocol. We semiquantitatively determined telomerase
      activity by serial dilution of each sample. All of 23 samples from acute and
      chronic type ATL patients were positive, seven of ten (70%) smoldering type
      patients and seven of 24 (29.2%) asymptomatic viral carriers were positive.
      Disease progression from asymptomatic viral carrier to acute type correlated with
      telomerase activity. Two samples from chronic type ATL patients with relatively
      high telomerase activity progressed to the acute type within 1 month. Serum
      lactate dehydrogenase level also correlated with telomerase activity. These
      results indicate that reactivation of telomerase activity is a key event in
      development and progression of ATL, and telomerase could be a useful marker for
      predicting the course of disease. Accordingly, ATL could be a good candidate
      disease for trials of telomerase inhibitors, as novel anticancer drugs.

PMID- 10071088
TI  - Tremor in multiple sclerosis.

PMID- 10071089
TI  - Episodic memory in transient global amnesia.

PMID- 10071090
TI  - Mechanisms of recovery from aphasia.

PMID- 10071091
TI  - The cholinergic hypothesis of Alzheimer's disease: a review of progress.
AB  - Alzheimer's disease is one of the most common causes of mental deterioration in
      elderly people, accounting for around 50%-60% of the overall cases of dementia
      among persons over 65 years of age. The past two decades have witnessed a
      considerable research effort directed towards discovering the cause of
      Alzheimer's disease with the ultimate hope of developing safe and effective
      pharmacological treatments. This article examines the existing scientific
      applicability of the original cholinergic hypothesis of Alzheimer's disease by
      describing the biochemical and histopathological changes of neurotransmitter
      markers that occur in the brains of patients with Alzheimer's disease both at
      postmortem and neurosurgical cerebral biopsy and the behavioural consequences of
      cholinomimetic drugs and cholinergic lesions. Such studies have resulted in the
      discovery of an association between a decline in learning and memory, and a
      deficit in excitatory amino acid (EAA) neurotransmission, together with important
      roles for the cholinergic system in attentional processing and as a modulator of
      EAA neurotransmission. Accordingly, although there is presently no "cure" for
      Alzheimer's disease, a large number of potential therapeutic interventions have
      emerged that are designed to correct loss of presynaptic cholinergic function. A
      few of these compounds have confirmed efficacy in delaying the deterioration of
      symptoms of Alzheimer's disease, a valuable treatment target considering the
      progressive nature of the disease. Indeed, three compounds have received European
      approval for the treatment of the cognitive symptoms of Alzheimer's disease,
      first tacrine and more recently, donepezil and rivastigmine, all of which are
      cholinesterase inhibitors.

PMID- 10071092
TI  - Episodic memory in transient global amnesia: encoding, storage, or retrieval
      deficit?
AB  - OBJECTIVES: To assess episodic memory (especially anterograde amnesia) during the
      acute phase of transient global amnesia to differentiate an encoding, a storage,
      or a retrieval deficit. METHODS: In three patients, whose amnestic episode
      fulfilled all current criteria for transient global amnesia, a neuropsychological
      protocol was administered which included a word learning task derived from the
      Grober and Buschke's procedure. RESULTS: In one patient, the results suggested an
      encoding deficit, and in two others, a storage deficit. CONCLUSIONS: The
      encoding/storage impairment concerning anterograde amnesia documented in our
      patients stands in clear contrast with the impairment in retrieval which must
      underly the retrograde amnesia that also characterises transient global amnesia.
      This dissociation in turn favours the idea of a functional independence among the
      cognitive mechanisms that subserve episodic memory.

PMID- 10071093
TI  - Mechanisms of recovery from aphasia: evidence from positron emission tomography
      studies.
AB  - OBJECTIVES: Language functions comprise a distributed neural system, largely
      lateralised to the left cerebral hemisphere. Late recovery from aphasia after a
      focal lesion, other than by behavioural strategies, has been attributed to one of
      two changes at a systems level: a laterality shift, with mirror region cortex in
      the contralateral cortex assuming the function(s) of the damaged region; or a
      partial lesion effect, with recovery of perilesional tissue to support impaired
      language functions. Functional neuroimaging with PET allows direct observations
      of brain functions at systems level. This study used PET to compare regional
      brain activations in response to a word retrieval task in normal subjects and in
      aphasic patients who had shown at least some recovery and were able to attempt
      the task. Emphasis has been placed on single subject analysis of the results as
      there is no reason to assume that the mechanisms of recovery are necessarily
      uniform among aphasic patients. METHODS: Six right handed aphasic patients, each
      with a left cerebral hemispheric lesion (five strokes and one glioma), were
      studied. Criteria for inclusion were symptomatic or formal test evidence of at
      least some recovery and an ability to attempt word retrieval in response to heard
      word cues. Each patient underwent 12 PET scans using oxygen-15 labelled water
      (H2(15)O) as tracer to index regional cerebral blood flow (rCBF). The task,
      repeated six times, required the patient to think of verbs appropriate to
      different lists of heard noun cues. The six scans obtained during word retrieval
      were contrasted with six made while the subject was "at rest". The patients'
      individual results were compared with those of nine right handed normal
      volunteers undergoing the same activation study. The data were analysed using
      statistical parametric mapping (SPM96, Wellcome Department of Cognitive
      Neurology, London, UK). RESULTS: Perception of the noun cues would be expected to
      result in bilateral dorsolateral temporal cortical activations, but as the rate
      of presentation was only four per minute the auditory perceptual activations were
      not evident in all people. Anterior cingulate, medial premotor (supplementary
      speech area) and dorsolateral frontal activations were evident in all normal
      subjects and patients. There were limited right dorsolateral frontal activations
      in three of the six patients, but a similar pattern was also found in four of the
      nine normal subjects. In the left inferolateral temporal cortex, activation was
      found for the normal subjects and five of the six patients, including two of the
      three subjects with lesions involving the left temporal lobe. The only patient
      who showed subthreshold activation in the left inferolateral temporal activation
      had a very high error rate when performing the verb retrieval task. CONCLUSIONS:
      The normal subjects showed a left lateralised inferolateral temporal activation,
      reflecting retrieval of words appropriate in meaning to the cue from the semantic
      system. Lateralisation of frontal activations to the left was only relative, with
      right prefrontal involvement in half of the normal subjects. Frontal activations
      are associated with parallel psychological processes involved in word retrieval,
      including task initiation, short term (working) memory for the cue and responses,
      and prearticulatory processes (even though no overt articulation was required).
      There was little evidence of a laterality shift of word retrieval functions to
      the right temporal lobe after a left hemispheric lesion. In particular, left
      inferolateral temporal activation was seen in all patients except one, and he
      proved to be very inefficient at the task. The results provide indirect evidence
      that even limited salvage of peri-infarct tissue with acute stroke treatments
      will have an important impact on the rehabilitation of cognitive functions.

PMID- 10071094
TI  - Executive function in depression: the role of performance strategies in aiding
      depressed and non-depressed participants.
AB  - OBJECTIVES: Depression has been found to be associated with dysfunction in
      executive processes, whereas relatively automatic processes are thought to remain
      intact. Failure to generate or implement adequate performance strategies has been
      postulated in depressed participants. The present study investigated spontaneous
      strategy usage in depressed and control participants, and the effectiveness of
      providing a hint about performance strategies. METHODS: Unipolar depressed
      participants were compared with matched healthy controls on three tasks sensitive
      to executive function: memory for categorised words, response suppression, and
      multiple scheduling. Participants in each group were randomly allocated to
      strategy aid and no strategy aid conditions. Those in the strategy aid condition
      were given a hint about the use of an appropriate performance strategy for each
      task, in addition to the standard instructions given to those in the no strategy
      aid condition. RESULTS: Depressed participants performed worse than controls on
      each of the three tasks, and were found to use appropriate performance strategies
      less often. Provision of strategy hints increased the use of performance
      strategies in two of the three tasks, memory for categorised words, and response
      suppression, but did not significantly improve overall performance for either
      group. CONCLUSIONS: The findings were consistent with the view that depressed
      participants fail to use appropriate performance strategies spontaneously to the
      same extent as controls. However, provision of information alone does not seem to
      be an adequate means of enhancing performance. The role of performance strategies
      in cognitive impairment in depression is discussed, both in terms of initiating
      use of such strategies and carrying these out efficiently.

PMID- 10071095
TI  - Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob
      disease.
AB  - OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in
      Germany, Hashimoto's encephalitis was encountered as a differential diagnosis,
      which has not yet been described in this context. METHODS: The symptoms and
      findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt
      Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies
      against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid
      ultrasonogram were found in all cases. Analysis of CSF disclosed an increased
      leucocyte count in three patients, and a raised CSF:serum concentration ratio of
      albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob
      disease, could not be detected in any of our patients. No periodic sharp wave
      complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG
      in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to
      death within a few months, the patients with Hashimoto's encephalitis often
      recover quickly when treated adequately. All the patients improved after
      administration of corticosteroids. CONCLUSION: The clinical symptomatology of
      both diseases may be very similar: dementia, myoclonus, ataxia, and personality
      change or psychotic phenomena are characteristic symptoms.

PMID- 10071096
TI  - Are sex and educational level independent predictors of dementia and Alzheimer's
      disease? Incidence data from the PAQUID project.
AB  - OBJECTIVES: To examine the age specific risk of Alzheimer's disease according to
      sex, and to explore the role of education in a cohort of elderly community
      residents aged 65 years and older. METHODS: A community based cohort of elderly
      people was studied longitudinally for 5 years for the development of dementia.
      Dementia diagnoses were made according to the DSM III R criteria and Alzheimer's
      disease was assessed using the NINCDS-ADRDA criteria. Among the 3675 non-demented
      subjects initially included in the cohort, 2881 participated in the follow up.
      Hazard ratios of dementia were estimated using a Cox model with delayed entry in
      which the time scale is the age of the subjects. RESULTS: During the 5 year
      follow up, 190 incident cases of dementia, including 140 cases of Alzheimer's
      disease were identified. The incidence rates of Alzheimer's disease were 0.8/100
      person-years in men and 1.4/100 person-years in women. However, the incidence was
      higher in men than in women before the age of 80 and higher in women than in men
      after this age. A significant interaction between sex and age was found. The
      hazard ratio of Alzheimer's disease in women compared with men was estimated to
      be 0.8 at 75 years and 1.7 at 85 years. The risks of dementia and Alzheimer's
      disease were associated with a lower educational attainment (hazard ratio=1.8,
      p<0.001). The increased risk of Alzheimer's disease in women was not changed
      after adjustment for education. CONCLUSION: Women have a higher risk of
      developing dementia after the age of 80 than men. Low educational attainment is
      associated with a higher risk of Alzheimer's disease. However, the increased risk
      in women is not explained by a lower educational level.

PMID- 10071097
TI  - Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer's
      disease and frontotemporal dementia.
AB  - OBJECTIVES: The diagnosis of Alzheimer's disease (AD) is now reliant on the use
      of NINCDS-ADRDA criteria. Other diseases causing dementia are being increasingly
      recognised--for example, frontotemporal dementia (FTD). Historically, these
      disorders have not been clearly demarcated from AD. This study assesses the
      capability of the NINCDS-ADRDA criteria to accurately distinguish AD from FTD in
      a series of pathologically proved cases. METHODS: The case records of 56 patients
      (30 with AD, 26 with FTD) who had undergone neuropsychological evaluation, brain
      imaging, and ultimately postmortem, were assessed in terms of whether at initial
      diagnosis the NINCDS-ADRDA criteria were successful in diagnosing those patients
      who had AD and excluding those who did not. RESULTS: (1) The overall sensitivity
      of the NINCDS-ADRDA criteria in diagnosing "probable" AD from 56 patients with
      cortical dementia (AD and FTD) was 0.93. However, the specificity was only 0.23;
      most patients with FTD also fulfilled NINCDS-ADRDA criteria for AD. (2) Cognitive
      deficits in the realms of orientation and praxis significantly increased the odds
      of a patient having AD compared with FTD, whereas deficits in problem solving
      significantly decreased the odds. Neuropsychological impairments in the domains
      of attention, language, perception, and memory as defined in the NINCDS-ADRDA
      statement did not contribute to the clinical differentiation of AD and FTD.
      CONCLUSION: NINCDS-ADRDA criteria fail accurately to differentiate AD from FTD.
      Suggestions to improve the diagnostic specificity of the current criteria are
      made.

PMID- 10071098
TI  - The use of electrophysiological monitoring in the intraoperative management of
      intracranial aneurysms.
AB  - OBJECTIVES: Somatosensory evoked potentials (SSEPs) and brainstem auditory evoked
      potentials (BAEPs) have been increasingly utilised during surgery for
      intracranial aneurysms to identify cerebral ischaemia. Between July 1994 and
      April 1996, we surgically treated 70 aneurysms in 49 consecutive patients (58
      operations) with the aid of intraoperative evoked potential monitoring. This
      study sought to evaluate the usefulness of SSEP and BAEP monitoring during
      intracranial aneurysm surgery. METHODS: Mean patient age was 51.9 (range 18-79)
      years. The sizes of the aneurysms were 3-4 mm (15), 5-9 mm (26), 10-14 mm (11),
      15-19 mm (seven), 20-24 mm (six), and >25 mm (five). SSEPs were monitored in 58
      procedures (100%) and BAEPs in 15 (26%). The neurological status of the patients
      was evaluated before and after surgery. RESULTS: Thirteen of the 58 procedures
      (22%) monitored with SSEPs had SSEP changes (12 transient, one persistent); 45
      (78%) had no SSEP changes. Three of 15 patients (20%) monitored with BAEPs had
      changes (two transient, one persistent); 12 (80%) had no BAEP changes. Of the 14
      patients with transient SSEP or BAEP changes, these changes resolved with
      adjustment or removal of aneurysm clips (nine), elevating MAP (four), or
      retractor adjustment (one). Mean time from precipitating event to
      electrophysiological change was 8.9 minutes (range 3-32), and the mean time for
      recovery of potentials in patients with transient changes was 20.2 minutes (range
      3-60). Clinical outcome was excellent in 39 patients, good in five, and poor in
      three (two patients died), and was largely related to pretreatment grade.
      CONCLUSIONS: SSEPs and BAEPs are useful in preventing clinical neurological
      injury during surgery for intracranial aneurysms and in predicting which patients
      will have unfavourable outcomes.

PMID- 10071099
TI  - Chronic motor neuropathies: response to interferon-beta1a after failure of
      conventional therapies.
AB  - OBJECTIVES: The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in
      patients with chronic motor neuropathies not improving after conventional
      treatments such as immunoglobulins, steroids, cyclophosphamide or plasma
      exchange. METHODS: A prospective open study was performed with a duration of 6-12
      months. Three patients with a multifocal motor neuropathy and one patient with a
      pure motor form of chronic inflammatory demyelinating polyneuropathy were
      enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of
      subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary
      outcome was assessed at the level of disability using the nine hole peg test, the
      10 metres walking test, and the modified Rankin scale. Secondary outcome was
      measured at the impairment level using a slightly modified MRC sumscore. RESULTS:
      All patients showed a significant improvement on the modified MRC sumscore. The
      time required to walk 10 metres and to fulfil the nine hole peg test was also
      significantly reduced in the first 3 months in most patients. However, the
      translation of these results to functional improvement on the modified Rankin was
      only seen in two patients. There were no severe adverse events. Motor conduction
      blocks were partially restored in one patient only. Anti-GM1 antibody titres did
      not change. CONCLUSION: These findings indicate that severely affected patients
      with chronic motor neuropathies not responding to conventional therapies may
      improve when treated with INF-beta1a. From this study it is suggested that INF
      beta1a should be administered in patients with chronic motor neuropathies for a
      period of up to 3 months before deciding to cease treatment. A controlled trial
      is necessary to confirm these findings.

PMID- 10071100
TI  - Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth
      family with an Asn205Ser mutation in the connexin 32 gene.
AB  - BACKGROUND: X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited
      motor and sensory neuropathy that mainly affects the peripheral nervous system.
      CMT1X is associated with mutations in the gap junction protein connexin 32
      (Cx32). Cx32 is expressed in Schwann cells and oligodendrocytes in the peripheral
      (PNS) and in the (CNS) respectively. METHODS: A CMT1X family with a Cx32 mutation
      was examined clinically and electrophysiologically to determine whether PNS, or
      CNS, or both pathways were affected. RESULTS: In a CMT1X family a novel mutation
      (Asn205Ser) was found in the fourth transmembrane domain of Cx32. The patients
      showed typical clinical and electrophysiological abnormalities in the PNS, but in
      addition visual, acoustic, and motor pathways of the CNS were affected
      subclinically. This was indicated by pathological changes in visually evoked
      potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central
      motor evoked potentials (CMEPs). CONCLUSIONS: These findings underscore the
      necessity of a careful analysis of CNS pathways in patients with CMT and Cx32
      mutations. Abnormal electrophysiological findings in CNS pathway examinations
      should raise the suspicion of CMTX and a search for gene mutations towards Cx32
      should be considered.

PMID- 10071101
TI  - One year outcome in mild to moderate head injury: the predictive value of acute
      injury characteristics related to complaints and return to work.
AB  - OBJECTIVES: To determine the prognostic value of characteristics of acute injury
      and duration of post-traumatic amnesia (PTA) for long term outcome in patients
      with mild to moderate head injury in terms of complaints and return to work.
      METHODS: Patients with a Glasgow coma score (GCS) on admission of 9-14 were
      included. Post-traumatic amnesia was assessed prospectively. Follow up was
      performed at 1, 3, 6, and 12 months after injury. Outcome was determined by the
      Glasgow outcome scale (GOS) 1 year after injury and compared with a more detailed
      outcome scale (DOS) comprising cognitive and neurobehavioural aspects. RESULTS:
      Sixty seven patients were included, mean age 33.2 (SD 14.7) years and mean PTA
      7.8 (SD 7.3) days. One year after injury, 73% of patients had resumed previous
      work although most (84%) still reported complaints. The most frequent complaints
      were headache (32%), irritability (34%), forgetfulness and poor concentration
      (42%), and fatigue (45%). According to the GOS good recovery (82%) or moderate
      disability (18%) was seen. Application of the DOS showed more cognitive (40%) and
      behavioural problems (48%), interfering with return to work. Correlation between
      the GOS and DOS was high (r=0.87, p<0.01). Outcome correlated with duration of
      PTA (r=-0.46) but not significantly with GCS on admission (r=0.19). In multiple
      regression analysis, PTA and the number of complaints 3 months after injury
      explained 49% of variance on outcome as assessed with the GOS, and 60% with the
      DOS. CONCLUSIONS: In mild to moderate head injury outcome is determined by
      duration of PTA and not by GCS on admission. Most patients return to work despite
      having complaints. The application of a more detailed outcome scale will increase
      accuracy in predicting outcome in this category of patients with head injury.

PMID- 10071102
TI  - Anti-amphiphysin I antibodies in patients with paraneoplastic neurological
      disorders associated with small cell lung carcinoma.
AB  - Patients with stiff man syndrome and breast cancer develop anti-amphiphysin I
      antibodies that primarily recognise the C terminus of the protein. Anti
      amphiphysin I antibodies have also been identified in a few patients with
      paraneoplastic neurological disorders (PND) and small cell lung cancer (SCLC).
      The frequency of anti-amphiphysin I antibodies in patients with SCLC and PND was
      analysed and the epitope specificity of these antibodies was characterised. Anti
      amphiphysin I antibodies were evaluated by immunohistochemistry on human and rat
      cerebellum and immunoblots of rat brain homogenates. Serum samples included 134
      patients with PND and anti-Hu antibodies (83% had SCLC), 44 with SCLC and PND
      without anti-Hu-antibodies, 63 with PND and either Yo, Ri, or Tr antibodies, 146
      with SCLC without PND, and 104 with non-PND. Positive serum samples were
      confirmed with immunoblots of recombinant human amphiphysin I and immunoreacted
      with five overlapping peptide fragments covering the full length of the molecule.
      Serum samples positive for anti-amphiphysin I antibodies included those from
      seven (2.9%) patients with PND and two (1.4%) with SCLC without PND. Six of the
      seven anti-amphiphysin I antibody positive patients with PND had SCLC (three with
      Hu-antibodies), and one had anti-Hu-antibodies but no detectable tumour. The PND
      included encephalomyelitis/sensory neuropathy (five patients), cerebellar
      degeneration (one), and opsoclonus (one). All anti-amphiphysin I antibodies
      reacted with the C terminus of amphiphysin I, but seven also recognised other
      fragments of the molecule. In conclusion, anti-amphiphysin I antibodies are
      present at low frequency in patients with SCLC irrespective of the presence of an
      associated PND. All anti-amphiphysin I antibody positive serum samples have in
      common reactivity with the C terminus of the protein.

PMID- 10071103
TI  - Activation of selected trunk muscles during symmetric functional activities in
      poststroke hemiparetic and hemiplegic patients.
AB  - OBJECTIVE: To compare the EMG activity between the recti abdominii muscles and
      between the lumbar erector spinae muscles in hemiparetic and hemiplegic patients
      during functional symmetric trunk movements and to compare patients' EMG activity
      profiles with those of healthy controls. METHODS: EMG activity from the selected
      muscles was recorded during three symmetric and time controlled trunk exercises.
      Data analysis was based on values of cross correlations and of ratios between EMG
      activity of the bilateral corresponding muscles. RESULTS: In all groups, the
      highest cross correlations were obtained for both muscles when the muscles acted
      as prime movers. For the recti abdominii muscles, these values in the patients
      were comparable with those of the healthy subjects, whereas for the extensor
      muscles, the highest synchronous activity was displayed in healthy subjects and
      the lowest in hemiplegic patients. Laterality differences in the amount of EMG
      activity of the recti abdominii muscles were not biased towards one side. For the
      extensor muscles, in the controls, the activation levels were higher in the left
      erector spinae muscle than in the right one in two of the three exercises.
      Similarly, in the extensor muscles of the hemiparetic patients, activity on the
      paretic side was higher than on the non-paretic side in two exercises.
      CONCLUSIONS: In patients with a supratentorial poststroke hemiparesis or
      hemiplegia, bilateral corresponding axial trunk muscles co-contract during
      symmetric trunk activities. Synchronous activation is at its highest level during
      voluntary dynamic tasks and is greater in the recti abdominii than in the erector
      spinae muscles. For both muscles, EMG activation levels on the paretic side were
      not lower than on the non-paretic side. Thus, the assertion that the muscles on
      the paretic side are activated to a lesser extent than their counterparts on the
      non-paretic side during symmetric trunk movements was not confirmed.

PMID- 10071104
TI  - Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph
      disease (SCA3/MJD).
AB  - To identify determinants of peripheral involvement in spinocerebellar ataxia type
      3/Machado-Joseph disease (SCA3/MJD) the influence of CAG repeat length, age of
      onset, disease duration and age on the results of nerve conduction studies was
      analysed in 58 patients with SCA3/MJD. Patients with SCA3/MJD showed marked
      reduction of compound muscle action potential (CMAP) and sensory nerve action
      potential (SNAP) amplitudes indicating axonal neuropathy of both motor and
      sensory fibres. In addition, there was moderate slowing of nerve conduction
      suggestive of mild peripheral demyelination. Multivariate regression showed that
      CMAP and SNAP amplitudes decreased with age, but were not affected by CAG repeat
      length, age of onset, or disease duration. The age related decline of CMAP and
      SNAP amplitudes in SCA3/MJD was greater than in normal subjects. The data suggest
      that the degree of peripheral damage in SCA3/MJD does not depend on CAG repeat
      length, age of onset, or disease duration, but is mainly related to the time
      period over which the SCA3/MJD mutation exerts its effect.

PMID- 10071105
TI  - Leptomeningeal metastasis after surgical resection of brain metastases.
AB  - OBJECTIVE: To determine the incidence and risk factors for leptomeningeal
      metastasis after surgery for brain metastasis of solid tumors. METHODS: Review of
      the records of all patients operated on for brain metastasis between January 1990
      and August 1995. RESULTS: In this period 28 patients underwent surgery for brain
      metastasis, of whom 27 were available for evaluation in this study. Median
      survival after craniotomy was 11 months. Nine patients (33%) developed
      leptomeningeal metastasis 2-13 months after surgery, which included six of the
      nine patients operated on for posterior fossa metastasis (p=0.05). In five
      patients, leptomeningeal metastasis was the only site of recurrence. Three
      patients developed the leptomeningeal metastasis as bulky tumour along the spinal
      cord, which is a rare presentation. No other risk factors for the development of
      leptomeningeal metastasis other than surgery for posterior fossa metastasis were
      identified. CONCLUSIONS: There is an increased risk of leptomeningeal metastasis
      after surgery for posterior fossa metastasis. Future trials should consider the
      value of an active approach to this complication in these patients.

PMID- 10071106
TI  - Tc-99m HMPAO SPECT in the evaluation of Alzheimer's disease: correlation between
      neuropsychiatric evaluation and CBF images.
AB  - The purpose of this study was to evaluate the effects of various covariants on
      the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by
      correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched
      normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed
      tomography (CT) were acquired for each subject. SPECT images were transformed to
      a standard size and shape by automated image registration (AIR) and were used for
      group comparison by means of SPM96. Voxel based covariance analysis was performed
      on standardised images taking the age of patients, severity of disease (clinical
      dementia rating scale, mini mental state examination, physical self maintenance
      scale), and atrophy indices as variables. There was significantly decreased
      regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal
      regions in the patient group (p<0.001), more marked in those patients having
      severe dementia. Covariance analysis disclosed that aging and severity of disease
      have a pronounced effect on rCBF, especially that of the left parietal region.

PMID- 10071107
TI  - Pure apraxic agraphia with abnormal writing stroke sequences: report of a
      Japanese patient with a left superior parietal haemorrhage.
AB  - A 67 year old Japanese male patient had pure agraphia after a haemorrhage in the
      left superior parietal lobule. He developed difficulty in letter formation but
      showed no linguistic errors, consistent with the criteria of apraxic agraphia. He
      manifested a selective disorder of sequencing writing strokes, although he was
      able to orally state the correct sequences. The patient's complete recovery after
      1 month, without new learning, showed that he had manifested a selective disorder
      of writing stroke sequences. These findings indicate that the final stage of the
      execution of writing according to acquired sequential memory shown as a stroke
      sequence can be selectively disturbed, and should be considered to be distinct
      from the ability of character imagery and the knowledge of the writing stroke
      sequence itself. This case also indicates that the left superior parietal lobule
      plays an important part in the execution of writing.

PMID- 10071108
TI  - Multiple sclerosis.

PMID- 10071109
TI  - Progressive aphasia with rapidly progressive dementia in a 49 year old woman.

PMID- 10071110
TI  - Radiosurgically treated acromegaly.

PMID- 10071111
TI  - Suprascapular nerve entrapment at the spinoglenoid notch due to a ganglion cyst.

PMID- 10071112
TI  - Neoplastic cerebral aneurysm from metastatic lung adenocarcinoma associated with
      cerebral thrombosis and recurrent subarachnoid haemorrhage.

PMID- 10071113
TI  - Intralaminar dural haematoma developing in the contralateral convexity after
      temporal lobectomy.

PMID- 10071114
TI  - Carbamazepine hypersensitivity syndrome presenting as vasculitis of the CNS.

PMID- 10071115
TI  - Thalamotomy for severe antipsychotic induced tardive dyskinesia and dystonia.

PMID- 10071116
TI  - Gabapentin in the treatment of painful diabetic neuropathy: a placebo controlled,
      double blind, crossover trial.

PMID- 10071117
TI  - Single motor unit activity pattern in patients with Schwartz-Jampel syndrome.

PMID- 10071118
TI  - Transient severe parkinsonism after acute organophosphate poisoning.

PMID- 10071119
TI  - Oropharyngeal palsy in Guillain-Barre and Fisher's syndromes is associated with
      muscle weakness in the neck and arm.

PMID- 10071120
TI  - Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial
      origin.

PMID- 10071121
TI  - Hemifacial spasm.

PMID- 10071122
TI  - Measuring the rate of progression and estimating the preclinical period of
      Parkinson's disease with [18F] dopa PET.

PMID- 10071124
TI  - Proceedings of the Association of British Neurologists, Royal College of
      Physicians, London, 9-11 September 1998.

PMID- 10071123
TI  - Utilisation and costs of profession care and assistance according to disability
      of patients with multiple sclerosis in Flanders (Belgium)

PMID- 10071125
TI  - Expression of eosinophil peroxidase in the immature basophil cell line KU812-F.
AB  - Although peroxidase activity in basophils can be detected by optical and
      ultrastructural cytochemistry, its characteristics remain to be determined. We
      have demonstrated the characteristics of peroxidase activity induced in the
      immature basophil cell line, KU812-F. Ultrastructurally, peroxidase activity was
      detected in granules as well as in the perinuclear space and endoplasmic
      reticulum. Immunocytochemistry revealed that KU812-F cells were stained by anti
      eosinophil peroxidase antibodies, and eosinophil peroxidase mRNA, not
      myeloperoxidase, was detected in the cells using Northern hybridization and
      reverse transcription-polymerase chain reaction. Eosinophil peroxidase can be one
      of the molecules shared with eosinophils and basophils. The biological function
      of eosinophil peroxidase detected in basophils remains uncertain.

PMID- 10071126
TI  - A unique carboxy-terminus truncation mutant of the retinoic acid receptor alpha
      gene associated with a variant marker chromosome in a retinoic acid resistant HL
      60 subline.
AB  - In order to contribute to the study of the molecular basis of leukemic cellular
      resistance to the induction of differentiation by all-trans retinoic acid (RA) we
      have generated and analyzed a mutant, RA-resistant HL-60 cell line. Molecular
      analysis of the retinoic acid receptor alpha (RARalpha) cDNA disclosed, in one of
      the two alleles, a novel mutation consisting of a 7-base deletion in the ligand
      binding domain that includes part of a FokI restriction endonuclease site
      previously described. As a consequence of this deletion and translational frame
      shift, a stop signal is created that truncates the protein at codon 421,
      disrupting an essential functional component of the receptor. Transducing an
      epitope tagged RARalpha into the mutant is sufficient to inhibit clonal growth in
      the presence of RA. Standard cytogenetic analysis, fluorescent in situ
      hybridization (FISH) and comparative genomic hybridization (CGH) analysis
      revealed the presence of two RARalpha loci, and showed a composite karyotype with
      additional abnormalities with respect to the parental line, including a
      chromosome 8 insertion in a chromosome previously known as marker three.

PMID- 10071127
TI  - Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute
      lymphoblastic leukemia.
AB  - We investigated the alterations of the p53, p21, p16, p15 and RAS genes in
      childhood T-cell acute lymphoblastic leukemia (T-ALL) and T-ALL cell lines by
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      analysis and direct sequencing. Mutations of the p53 gene were found in three of
      57 (5%) patients at diagnosis, one of 14 (7%) patients at relapse and in 12 of 18
      (67%) cell lines. In these 12 cell lines, four had more than two mutations of the
      p53 gene. The p53 mutations were found in four of five cell lines whose original
      fresh leukemic cells were simultaneously examined original fresh leukemic cells.
      However, only one of the four fresh leukemic cells had the same mutation. All
      patients with p53 mutations in the course of disease died. Mutations of the p21
      gene were not identified in 71 fresh samples and in 18 cell lines. N-RAS
      mutations were found in two of 57 (4%) fresh T-ALL patients at diagnosis, and
      four of 18 cell lines (22%), whereas no mutations were detected in any samples at
      relapse. Alterations of the p16 gene were found in 18 of 47 (38%) patients at
      diagnosis and in seven of 14 (50%) at relapse. These differences were not
      statistically significant. There were no differences in the frequency of
      alteration of the p16 and p15 genes between event-free patients and the remaining
      patients. Furthermore, we found the methylation of p16 gene in three of seven
      patients lacking homozygous deletions, suggesting higher frequency of p16
      inactivation than previous reports in T-ALL. Interestingly, we found that one
      allele is inactivated by methylation and another allele had nonsense mutation in
      one cell line (KOPT-KI), resulting in loss of protein expression of p16. This
      type of p16 inactivation has not been so far reported in leukemia. We conclude
      that, (1) p53 mutations are infrequent at diagnosis but tend to be associated
      with poor clinical outcome; (2) RAS and p21 mutations may not be involved in the
      pathogenesis of T-ALL; (3) not only frequent alterations of p16 and p15 genes but
      also methylation of p16 gene are involved in initiating the leukemogenesis of T
      ALLs, and (4) these 5 genes are independently involved in T-ALL.

PMID- 10071128
TI  - MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in
      prolymphocytoid transformation.
AB  - We report the establishment and characterization of two cell lines, MEC1 and
      MEC2, that grew spontaneously on two subsequent occasions from the peripheral
      blood (PB) of a patient with B-chronic lymphocytic leukemia (B-CLL) in
      prolymphocytoid transformation. The patient was EBV-seropositive, his leukemic
      cells were EBNA negative, but the spontaneously grown cell lines are EBNA-2
      positive. In liquid culture MEC1 cells grow adherent to the vessel wall and as
      tiny clumps; MEC2 cells do not adhere and form large clumps. The doubling time of
      MEC1 is 40h and of MEC2 is 31h. Both cell lines express the same light (kappa)
      and heavy chains (mu, delta) as the fresh parental B-CLL cells at the same high
      intensity, share the expression of mature B cell markers (CD19, CD20, CD21,
      CD22), differ in the expression of CD23 and FMC7, are CD11a+, CD18+, CD44+,
      CD49d+, CD54+ and express at high levels both CD80 and CD86. CD5 is negative on
      MEC1 cells (as on the vast majority of parental cells) and it has been lost by
      MEC2 cells after several months of culture. The cells have a complex karyotype.
      The tumour origin of MEC1 and MEC2 has been demonstrated by Southern blot
      analysis of the IgH loci and by Ig gene DNA sequencing. They use the VH4 Ig
      family and have not undergone somatic mutations (94.8% homology with germline Ig
      gene 4-59). Cytofluorographic analysis and RT-PCR reveal that MEC1 and MEC2
      overexpress Bcl-2 together with Bax, express large amounts of Bcl-xL and trace
      amounts of Bcl-xS.

PMID- 10071129
TI  - New data on the cytolytic effects of natural killer cells (Kurloff cells) on a
      leukemic cell line (guinea pig L2C).
AB  - L2C leukemia is a leukemia that occurs in strain two guinea pigs. The L2C cells
      are natural killer-sensitive. The Kurloff cell (KC), a guinea pig NK cell,
      develops a 3-fold increase in lysosomal enzyme activity and the number of KC
      cells increases during leukemogenesis, leading to KC cell-mediated L2C cytolysis.
      This paper shows that conjugates are produced by incubating KC and L2C for 4 h,
      with 34% of L2C showing chromatin compaction and shrinkage of the cytoplasm.
      There was also a reorientation of the KC cytoplasmic organelles to face the
      target cell and an elongation of the KC to produce arms that engulfed the L2C.
      The L2C had either necrotic or apoptotic characteristics. L2C DNA fragmentation
      was demonstrated in situ with the comet and the TUNEL assays. 22.2% of the viable
      L2C lost their membrane asymmetry during KC-L2C conjugation as shown by
      incubation with Annexin V-FITC. These results provide new evidence that the death
      of L2C is due, at least partly, to apoptosis. The cytolytic effect of the NKKC
      might be a model of the cytological changes that occur in NK cell-leukemic cell
      conjugates.

PMID- 10071130
TI  - Expression and release of adhesion molecules by human acute myelogenous leukemia
      blasts.
AB  - The expression and release of adhesion molecules by acute myelogenous leukemia
      (AML) blasts was investigated in vitro. For most patients AML blasts expressed
      relatively low levels of membrane-bound L-selectin and Intercellular adhesion
      molecule 1 (ICAM-1), but their soluble forms were detected in the supernatants
      for the majority of patients when AML blasts were cultured in vitro. These in
      vitro levels of SL-selectin and sICAM-1 were considerably lower than the normal
      serum levels. Divergent and relatively small alterations in SL-selectin and sICAM
      1 levels were usually observed when exogenous growth factors were present during
      AML blast culture, whereas increased SL-selectin levels were observed after
      coculture of AML blasts and normal leucocytes. E- and P-selectin were neither
      expressed nor released by AML blasts. We conclude that AML blasts are a source of
      soluble adhesion molecules.

PMID- 10071131
TI  - Qualitative and quantitative characterization of Fas (APO-1/CD95) on leukemic
      cells derived from patients with B-cell neoplasms.
AB  - Expression density and function of Fas (APO-1/CD95) on malignant B-cells, an
      antigen thought responsible for abnormal tumor biology, remains to be fully
      understood. Fifty-five cases with B-cell neoplasms of acute lymphoblastic
      leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), B
      cell malignant lymphoma (ML), and myeloma (MM) were studied for qualitative and
      quantitative expression and function of Fas using flow cytometry and annexin-V
      staining methods. Fas expression was flow cytometrically unimodal with
      heterogeneous density and showed quantitatively characteristic features among
      different diseases; weak in ALL, faint in CLL, moderate in HCL, and strong in ML,
      respectively. Not only full-length but also alternatively spliced truncated mRNAs
      were detected even in leukemic B-cells with qualitatively faint or negative Fas,
      and then band density of the former transcripts by RT-PCR was correlated to the
      Fas protein expression level. Short-term culture of freshly isolated cells gave
      rise to increases of Fas density and susceptibility for apoptosis, suggesting
      that the mRNA and inducible Fas are functional at least in vitro. These results
      show that Fas is a biological marker for characterizing B-cell neoplasms
      reflecting various stages of B-cell ontogeny and may have clinical utility as a
      therapeutic strategy.

PMID- 10071132
TI  - Fitness landscapes and the myeloid leukemias.
AB  - Fitness landscapes, which provide a unique perspective for viewing co-evolving
      cell populations, were used to study the evolution of CML and MDS. This led to
      several conclusions: (1) accelerated phase CML and RAEB/RAEBt are not specific
      disease entities. They represent the time when AML cells are replacing
      preleukemia cells; (2) monoclonal hemopoiesis and RA/RARS represent a variety of
      clinical syndromes with a common appearance but with different evolutionary
      potential; (3) malignant cells alter the fitness landscape enhancing their
      proliferative advantage. These studies provide the basis for new approaches to
      treatment.

PMID- 10071133
TI  - Safe mobilization of normal progenitors in advanced chronic myeloid leukemia with
      intensive chemotherapy and granulocyte-colony stimulating factor.
AB  - Twenty-one patients with advanced chronic myeloid leukemia (late chronic phase (n
      = 8), accelerated phase (n = 11) and blast crisis (n = 2)) were treated with
      idarubicin, cytarabine, and etoposide followed by G-CSF and subsequent collection
      of peripheral blood progenitor cells in the early recovery phase. Treatment was
      reasonably well tolerated with no deaths or intensive care admissions. Despite
      the advanced phase of disease and heavy pretreatment with cytotoxics and
      interferon-alfa, 11 of 21 patients (52%) achieved a cytogenetic response. Of the
      nine major cytogenetic responses (complete (n = 3) and partial (n = 6)), seven
      achieved adequate progenitor collections for consideration for autologous
      transplantation. The only predictor of response was disease duration (P = 0.02).
      With a median follow-up of 1171 days from treatment it appears unlikely that G
      CSF contributed to disease progression. Survival post-IcE was predicted by
      disease stage (P = 0.0001). Intensive chemotherapy followed by G-CSF allowed
      adequate yields of predominantly Philadelphia chromosome negative progenitor
      cells to be obtained from one-third of patients with advanced CML.

PMID- 10071134
TI  - Detection of BCR-ABL transcripts in chronic myeloid leukaemia by nested PCR.
AB  - Polymerase chain reaction (PCR) is a powerful and rapid method for specifically
      detecting BCR-ABL rearrangement by amplification of the complementary DNA (cDNA)
      produced by reverse transcription of BCR-ABL mRNA. We studied 29 patients for
      detecting the presence of BCR-ABL transcripts before and after bone marrow
      transplantation (BMT). Our sample was composed of two different groups of
      patients: one group (n = 18) was studied by serial follow-ups before and after
      BMT; a second group (n = 11) was studied several years after BMT. Detection of
      BCR-ABL was carried out with different primer sets at different periods of the
      clinical outcome of chronic myeloid leukaemia (CML). A comparison of PCR data and
      clinical-haematological conditions showed clear differences between patients. In
      the first group, eight patients showed a positive correlation between a
      favourable clinical outcome and molecular remission. Conversely, in the second
      group, six patients were BCR-ABL positive between 20 and 117 months after BMT,
      while only two of these patients showed signs of clinical relapse. Among all
      patients whose isoforms were known at some time during the course of CML, the
      more frequent isoform was b3a2. These results were compared to previous findings
      in the literature on diagnosis, outcome and prognosis of CML.

PMID- 10071135
TI  - Thrombopoietin receptor in acute myeloid leukemia.

PMID- 10071136
TI  - Sezary cells with hairy projections.
AB  - A case of sezary syndrome where the sezary cells showed cytoplasmic hairy
      projections is reported. The patient had typical exfoliative erythematous
      dermatitis, high white cell count, atypical lymphocytes of T-phenotype with
      folded nuclei and bone marrow involvement. The ultra structure study showed
      cerebriform nucleus and cytoplasmic projections.

PMID- 10071137
TI  - Efficacy of bisphosphonate for hypercalcemia in patients with adult T-cell
      leukemia.

PMID- 10071138
TI  - Tear fluid analysis in patients with primary Sjogren's syndrome using lectin
      probes. A comparative study of patients with primary Sjogren's syndrome, patients
      with other immune inflammatory connective tissue diseases and controls.
AB  - PURPOSE: To study and compare the glycoprotein composition of tear fluid from
      patients with primary Sjogren's syndrome, patients with other connective tissue
      diseases and control individuals. METHODS: SDS polyacrylamide gel electrophoresis
      followed by Coomassie staining or Western blotting and overlaying with ten
      different lectins. RESULTS: The frequency of many glycoprotein bands discovered
      was significantly decreased in primary Sjogren's syndrome compared with controls
      and patients with other connective tissue diseases. The reduction was most
      pronounced in the 14-68 kDa molecular weight range. CONCLUSIONS: A decrease in
      the production rate and/or a change in the glycosylation pattern of the tear
      glycoproteins was found in patients with primary Sjogren's syndrome. The changes
      discovered, however, were not specific enough to be useful as a diagnostic test.

PMID- 10071139
TI  - Expression of factor VIII-related antigen in human aqueous drainage channels.
AB  - PURPOSE: Previous studies have indicated that there are preformed channels at the
      inner aspect of the anterior sclera, capable of draining fluid from the
      suprachoroidal space into scleral veins. The aim of this study was to
      characterize the cellular lining of these channels, and to compare it with the
      endothelium of Schlemm's canal, the collector channels and the scleral blood
      vessels. METHODS: Histological sections from the angular region of human eyes
      were prepared by an immunoperoxidase method to evaluate the expression of factor
      VIII-related antigen in different aqueous drainage channels. RESULTS: The
      cellular lining of the scleral channels showed a weak immunostaining to factor
      VIII-related antigen. Factor VIII-related antigen was also detected in the
      endothelium of the collector channels and Schlemm's canal. CONCLUSION: The
      positive immunoreaction to factor VIII-related antigen indicates that the
      previously described scleral channels, the collector channels and Schlemm's canal
      are all lined by an endothelium derived from a vascular origin.

PMID- 10071140
TI  - Optic nerve head sector analysis recognizes glaucoma most effectively around disc
      poles.
AB  - PURPOSE: To analyze the topography of normal and glaucomatous discs with the goal
      of developing improved strategies to discriminate between normal and glaucomatous
      eyes. SUBJECTS AND METHODS: Raster tomography was performed in both eyes of 225
      healthy subjects and in 296 eyes of 214 glaucoma patients. Cup area, average cup
      radius, rim area and minimal rim width were measured in 24 sectors around the
      optic nerve head at nine different depths from the reference plane. Receiver
      Operating Curves (ROC) for numerous combinations of parameter, sector and depth
      were calculated and compared. RESULTS: Discrimination between glaucomatous and
      normal eyes varied widely between single sectors of the optic disc, and was best
      at the vertical poles of the disc, intermediate in nasal sectors and worst in
      temporal sectors. When single sectors or combinations of sectors at the superior
      pole were combined with their counterparts at the inferior pole of the optic
      nerve, the gain in sensitivity exceeded the loss in specificity, and
      discrimination improved. Separation declined dramatically if any of the 8
      temporal sectors were involved in such analysis. Depth influenced discrimination
      only slightly. CONCLUSION: Single sectors located close to the vertical meridian
      yielded better discrimination than global measurements. When two or more sectors
      at the superior pole were combined with each other, as well as with their
      counterparts at the inferior pole, discrimination improved even further.
      Localized changes concurred frequently, but asymmetrically at both poles of the
      disc. The depth from reference plane used to define the cup was not critical for
      separation between normal and glaucomatous eyes.

PMID- 10071141
TI  - Retrobulbar hemodynamics in amaurosis fugax; investigation by color Doppler
      velocity.
AB  - PURPOSE: The aim of the study is to determine blood flow and resistance
      parameters (Resistance Index-RI, Pulsatility Index-PI) in the retrobulbar
      arteries of patients suffering from amaurosis fugax. METHODS: Color Doppler
      velocity was used to measure blood flow velocity and vascular resistance in the
      ophthalmic artery, central retinal artery and lateral short posterior ciliary
      artery of 32 involved eyes in their afflictless interval. The patients' mean age
      was 60.1 years (range 29-85). The age- and sexmatched control group comprised 32
      healthy volunteers (32 eyes). RESULTS: There was no significant difference
      neither in RI nor in PI of amaurosis fugax patients compared to the control
      group. CONCLUSIONS: We conclude that in almost all cases of amaurosis fugax no
      local disturbance of blood flow in the afflictless interval is noted. However,
      increased vessel resistance is noticed in some cases of amaurosis fugax: Giant
      cell arteritis, intraorbital vascular anomalies, intraorbital tumors. In these
      cases color Doppler velocity is able to give information on the extent of blood
      flow disorder and, in particular by the B-mode, the etiology can be assumed.

PMID- 10071142
TI  - Effects of low alcohol consumption on visual evoked potential, visual field and
      visual contrast sensitivity.
AB  - PURPOSE: We studied changes in the vision of 16 people after consumption of a
      small quantity of alcohol, at a blood alcohol level (BAL) of 0.57 g/kg. METHODS:
      We studied visual contrast sensitivity (VCS) using Vistech VCTS 6500, visual
      evoked potential (VEP) by checked pattern stimulations and the peripheral visual
      field (PVF) with a perimetric automatic Humphrey. We first carried out the tests
      on sober people and then on individuals with a BAL of 0.57 g/kg. RESULTS: Alcohol
      consumption caused no significant difference in performance for these 3 tests.
      However, at a BAL of 0.57 g/kg there was a decrease in cerebral function, as
      shown by an increase in the number of mistakes made in the Wisconsin Card Sorting
      Test. CONCLUSION: These results suggest that for a low blood alcohol level,
      visual performance is less affected by the visual changes than by alteration in
      brain functions.

PMID- 10071143
TI  - Vapor pressure osmometry: minimum sample microvolumes.
AB  - PURPOSE: Vapor pressure osmometers are currently designed to handle sample
      volumes as small as 2.0 microliters (microl) but smaller sample volumes are
      desirable in tear fluid studies. We determined the minimum sample size required
      for adequate validity and repeatability of osmolality measurements. METHODS: A
      standard saline solution (290 mmol/kg) was sampled by a variable, calibrated
      pipette. Forty samples were processed with a Wescor 5520 vapor pressure osmometer
      at each of the following volumes: 2.0, 1.6, 1.2, 1.0, 0.8, 0.7, 0.6 and 0.5
      microl. Prior to each test series, the instrument was calibrated with the
      identical volume of 290 mmol/kg saline. Relevant descriptive statistics were
      computed and an analysis of variance (ANOVA) was performed on the resulting data.
      RESULTS: The mean osmolalities of the eight 40-sample groups ranged from 288.42
      to 290.68 mmol/kg and were not significantly different from 290 mmol/ kg or each
      other (p>0.05). The standard deviations were inversely correlated with the sample
      volumes, gradually increased to approximately 1% as sample volume was reduced to
      0.8 microl, then more rapidly increased as the sample volume was lowered still
      further. CONCLUSION: Sample microvolumes as small as 0.8 microl can be collected
      for accurate and repeatable results with the Wescor 5520 vapor pressure osmometer
      when a standard deviation of approximately 1% is acceptable. Microvolumes from
      0.7 to 0.5 microl may also be used if the expanded spread of data can be offset
      by multiple repeated readings. Using a 2.0 microl sample volume, the ultimate
      accuracy and repeatability of the Wescor vapor pressure osmometer was +/-2% at
      290 mmol/kg: 99%, of all readings (+/-3 standard deviations) should fall within
      +/-6 mmol/kg of the true value.

PMID- 10071144
TI  - The role of UV-radiation in the development of conjunctival malignant melanoma.
AB  - PURPOSE: To investigate the possible role of UV-radiation in the development of
      conjunctival malignant melanoma. N-ras mutations are frequently found in
      cutaneous melanomas of sun-exposed body areas. UV-radiation is thought to induce
      mutations in the N-ras gene, that convert these genes into active oncogenes. The
      presence of N-ras mutations has been considered an indicator for UV-exposure in
      the development of melanomas on sun-exposed body sides. METHODS: We analyzed six
      paraffin-embedded conjunctival melanomas for mutations of the N-ras gene. Codons
      12, 13 and 61 were amplified using polymerase chain reaction and sequenced.
      RESULTS: We could not detect point mutations of the N-ras gene in our samples.
      CONCLUSION: Since we could not find deviations from the wild type sequence in the
      N-ras gene, our study does not support UV-exposure as being causative in the
      development of conjunctival melanoma.

PMID- 10071145
TI  - Intraocular pressure measurement in the conscious rat.
AB  - PURPOSE: To develop a method for measurement of intraocular pressure in
      conscious, unsedated rats. METHODS. The animal was gently held with a thick
      fabric mitten, topical anesthetic drops were instilled and the Tono-Pen was
      applied to the cornea. RESULT: Measurements in a total of 51 animals did not
      differ significantly among four strains studied: the overall mean intraocular
      pressure+/-standard deviation was 13.0+/-1.2 mm Hg. Several intraocular pressure
      tolerance limits were calculated from this conscious rat data to provide a
      baseline estimate for future studies. CONCLUSIONS: This measurement method in
      conscious rats may contribute to making this widely used laboratory animal
      available for intraocular pressure research.

PMID- 10071146
TI  - Refractive changes in the elderly.
AB  - PURPOSE: Cross-sectional studies have consistently shown younger people to be
      less hyperopic than older people, but it is not known if this reflects a myopic
      shift from one generation to the next or a true age-related shift. METHODS: We
      used data from three population surveys to study cohort phenomena and true age
      related changes in refraction of elderly people in southern Sweden. Differences
      concerning the use of cycloplegics made us restrict comparisons between
      refractions in separate studies to persons aged 65 to 74 years, in whom our
      measurements were considered unlikely to have been affected by accommodation.
      RESULTS: An apparent increase in mean spherical equivalent as rapid as 0.6 D in
      10 years was observed in our latest (and largest) cross-sectional survey. The
      myopic shift, from one generation to the next, was limited to 0.25 D in 25 years.
      This discrepancy was explained by a true age-related hyperopic shift between 55
      and 70, which was confirmed in a longitudinal study of over 1000 persons followed
      for more than 8 years. CONCLUSION: A true age-related hyperopic shift between 55
      and 70 does indeed exist, and should not be disregarded by anyone who is
      prescribing spectacles or performing surgery for refractive errors. In the long
      run, however, a persisting secular trend towards myopia could prove even more
      important.

PMID- 10071147
TI  - Can interocular pattern reversal visual evoked potential and motor reaction time
      differences distinguish anisometropic from strabismic amblyopia?
AB  - PURPOSE: With the use of the pattern reversal visual evoked potential and the
      motor reaction time, we sought to differentiate anisometropic amblyopia from
      strabismic amblyopia on the basis of the visual transmission time. METHODS:
      Pattern reversal visual evoked potentials and motor reaction times were obtained
      in nine normal subjects, eight anisometropic and seven strabismic amblyopes.
      RESULTS: Our results show that while the peak time of the pattern visual evoked
      potential in anisometropic amblyopia and strabismic amblyopia was significantly
      delayed, it could not distinguish the two types of amblyopia. In contrast, a
      significantly longer interocular increment in strabismics compared to
      anisometropes was found with the reaction time, but not with the pattern visual
      evoked potential. CONCLUSION: Our findings thus show that it is possible to
      distinguish strabismic from anisometropic amblyopes using interocular differences
      in reaction time measurements. Our results bring support to the contention that
      the two types of amblyopia represent different neural abnormalities.

PMID- 10071148
TI  - A note about retinal structure and visual acuity. A light microscopic study of
      the cones in fovea centralis.
AB  - PURPOSE: Production of reliable sections of fovea centralis of primate retina.
      METHODS: Rhesus monkey eyes were processed using a new technique known to
      minimize artefacts and cell-shrinkage in other tissues. An in vivo vascular
      perfusion-fixation technique with an isotonic fixative followed by a process of
      slow infiltration with small increments in concentrations were used. RESULTS:
      Tangential 1 microm thick serial-sections showed a very good morphology. An
      average cone-to-cone-center distance of 3.8 microm in the central part of the
      fovea centralis was found. A cone-to-cone-center distance of 2.2-2.6 microm is
      suggested in the literature. CONCLUSION: In spite of the limited study we believe
      that the new technique has resulted in less tissue shrinkage. Our results are
      discussed in relation to maximal possible resolution of the eye. Our calculations
      (for green light) support the idea that the structure of the fovea centralis and
      the refractive media of the eye are developed close to perfection.

PMID- 10071149
TI  - Postoperative systemic corticosteroid treatment and Molteno implant surgery: a
      randomized clinical trial.
AB  - PURPOSE: To determine whether it is possible to improve the surgical success of
      Molteno implantation by causing a general suppression of collagen synthesis with
      postoperative oral prednisolone. METHODS: Twenty-two patients requiring single
      stage, single-plate Molteno implantation were randomized into two study groups:
      the control group A and the systemic prednisolone treatment group B. Serum
      markers of collagen metabolism were monitored. RESULTS: A successful outcome at
      the end of the 6-month follow-up, defined as final IOP > or =6 mmHg and < or =22
      mmHg with less or equal number of antiglaucoma medication as preoperatively and
      no additional surgery was achieved in 9 of 11 (82 %) patients of group A and in 5
      of 10 (50 %) patients of group B (p= 0.18). There was a statistically significant
      decrease in serum markers of collagen synthesis in the group B but not in the
      group A. CONCLUSION: The serum markers indicated a systemic effect of oral
      prednisolone on collagen synthesis in group B but it did not improve the surgical
      outcome as compared to the controls.

PMID- 10071150
TI  - Visual function after strontium-90 plaque irradiation in patients with age
      related subfoveal choroidal neovascularization.
AB  - PURPOSE: To report 2-year visual and angiographic results in eyes treated with
      strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM)
      in age-related macular degeneration. METHODS: Twenty eyes with recent subfoveal
      CNVM were treated with local irradiation. The impact of the treatment on visual
      function was evaluated by visual acuity, contrast sensitivity and reading speed
      testing. RESULTS: At 12 months visual acuity had improved or remained the same in
      9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes
      with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes
      with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast
      sensitivity was better in the irradiated eyes than in the fellow eyes with late
      age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%)
      could read at least some words at 24 months. CONCLUSIONS: Visual function
      decreases in patients treated with strontium irradiation, but less in eyes
      showing regression of the CNVM than in eyes with further growth of the CNVM.

PMID- 10071151
TI  - Management of choroidal melanomas with linear accelerator-based stereotactic
      radiosurgery.
AB  - PURPOSE: To discuss the technical aspect, dose prescription, clinical results,
      and biological responsiveness of linear accelerator-based stereotactic
      radiosurgery for choroidal melanoma. METHODS: From March 1995 to December 1995,
      three choroidal melanoma patients were treated with Linac-based radiosurgery in
      our department. Two patients underwent one dose of radiosurgery with 18 and 20 Gy
      in single fraction, respectively. The third patient received two doses of
      radiosurgery with a total dose of 35 Gy. RESULTS: Follow-up time ranged from 19
      to 25 months (median: 24 months). One patient had near-total regression, while
      the other two patients had partial response on the last MR images. Visual acuity
      was deteriorated in all patients. One patient developed a radiation-induced
      cataract in the treated eye. CONCLUSION: Linac-based radiosurgery is technically
      feasible for management of choroidal melanoma. Although visual acuity was not
      improved in these patients, they appreciated the preserving of the eyeball
      without affecting their general appearance.

PMID- 10071152
TI  - Clinical features and surgery for acquired progressive esotropia associated with
      severe myopia.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and physiological
      findings and to determine the most appropriate surgical procedure for acquired
      progressive esotropia with severe myopia. METHODS: Thirty-eight cases of acquired
      progressive esotropia with severe myopia were examined to evaluate their clinical
      and physiological findings. All cases were divided into four groups according to
      the limitation of their abduction. The eyeball in group IV is fixed in an
      extremely adducting position. Thirty-one cases underwent strabismus surgery;
      medial rectus muscle recession and lateral rectus muscle resection in 23 cases,
      transposition of superior and inferior rectus muscles (modified Jensen procedure
      included) in eight cases. RESULTS: The medial rectus muscle recession with the
      lateral rectus muscle resection procedure was effective in the early stage of
      acquired progressive esotropia patients. Transposition procedure was effective in
      the severe abducting limited patients. CONCLUSIONS: As the recession & resection
      procedure is easier than the transposition procedure, we recommend performing
      surgery in the earlier stage of the abducting disorder before the eyeball is
      fixed in an extremely adducting position.

PMID- 10071153
TI  - Development of grating acuity in infants with Retinopathy of Prematurity.
AB  - PURPOSE: To evaluate the visual development in infants with stage 1 approximately
      3 ROP and compare their visual results with healthy preterm infants. PATIENTS AND
      METHODS: One hundred forty-four premature infants were recruited and were divided
      into 3 groups according to the stage of ROP. Randomly selected preterm subjects
      with no ROP were taken as controls. Ophthalmic examinations started 4 to 7 weeks
      after birth and were repeated as needed until the retina was fully vascularized
      or until any ROP that developed had resolved. Grating acuity was measured by
      acuity cards between 35-45 weeks of corrected age and by PL method at 12, 18 and
      24 months of age. RESULTS: Infants with stage 3 ROP had slightly lower visual
      acuity scores compared to other infants at most of the testing points throughout
      the 35-45 week period, which did not show statistical significance at any week.
      Infants with stage 2 and 3 ROP had similar visual acuity values but slightly
      lower acuity scores than infants with stage I or no ROP at the 12 month follow
      up. The differences were not statistically significant. Stage 3 ROP infants had
      significantly lower acuity scores compared to infants with stage 1-2 or no ROP at
      the 18 and 24 month follow-up visits (p<0.0001). CONCLUSION: We stress periodic
      monitoring of early visual acuity in infants with ROP because of the possibility
      of impaired visual development.

PMID- 10071154
TI  - Age-related macular degeneration in Inuit.
AB  - PURPOSE: To describe a specific Greenlandic type af age-related macular
      degeneration (AMD) - the Retinochoroidal Atrophy (RCA). METHODS: 135 referred
      patients in East Greenland were examined in 1997. A colour and a redfree fundus
      photograph of an 87-year-old Greenlandic woman illustrates the clinical picture
      of RCA (retinochoriodal atrophy). RESULTS: Of 135 examined patients 22 had AMD.
      23 eyes in 12 patients had RCA, which was the most common type af AMD in this
      Greenlandic investigation. The clinical picture of RCA is peripapillary and
      central retinochoroidal atrophy and sclerosis resembling a recumbent Russian
      matushka doll. The mean age of the 12 patients with RCA was 74.4+/-8.7 years.
      They were all severely visually handicapped with a visual acuity < or =6/60.
      CONCLUSION: A specific type of Greenlandic AMD called RCA is described. No
      epidemiological conclusions can be drawn from this investigation.

PMID- 10071155
TI  - Digital fundus imaging: a quality and cost comparison with 35-mm film.
AB  - PURPOSE: This study compares 35-mm transparencies with colour digital fundus
      images. METHODS: Colour fundus photos were acquired simultaneously on a digital
      system and on 35-mm film on 32 consecutive patients. These were assessed
      independently by two ophthalmologists who graded overall picture quality and
      granularity of the images. They also assessed if the images were adequate for the
      purpose of making a diagnosis. An analysis of the costs of the two systems was
      performed. RESULTS: The film images had significantly better scores for overall
      picture quality (p=0.0001, 95% CI 0.5 to 1.5) and granularity (p<0.0001, 95% CI
      1.5 to 2). However, both digital and film images were considered adequate for
      diagnosis (p=0.052, 95% CI 0.12 to 8.32). CONCLUSION: The quality of digital
      images is acceptable for diagnostic purposes although resolution is limited.
      Other advantages and developing technologies will make it increasingly attractive
      in the future.

PMID- 10071156
TI  - Indocyanine green angiography of retinal pigment epithelial tears.
AB  - PURPOSE: To investigate the fluorescein and indocyanine green (ICG) features
      before and after retinal pigment epithelial tear. METHODS: Fluorescein and ICG
      videoangiography were performed in 30 patients affected by age-related macular
      degeneration either complicated by tear of the retinal pigment epithelium (25
      eyes) or by pigment epithelial detachment with pretear characteristics (5 eyes).
      RESULTS: At the pretear stage fluorescein angiography (FA) showed in all cases
      signs of occult CNV associated with delayed, slow and uneven filling of the
      pigment epithelium detachment. In 2 eyes the ICG filling of the retinal pigment
      epithelial detachment was seen. Progression to the tear stage was seen in 4 eyes
      where a CNV was evident on ICG angiography; in two eyes within one month after
      laser photocoagulation. At the tear stage FA showed an area of marked
      hyperfluorescence with well defined margins. Adjacent to the exposed area the
      torn RPE was markedly hypofluorescent during all angiographic phases. The bare
      choroid was always hypo or normofluorescent on ICG angiography. The torn retinal
      pigment epithelium showed moderate hypofluorescence. The exact seat and extension
      of CNVs could be visualized in 20 cases (67%; 95% C.I., 50-84%) with ICG
      angiography vs. 6 cases (20%; 95% C.I., 6-34%) with FA (p<0.001). CONCLUSIONS:
      ICG angiography did not add anything substantial to the analysis of frank tears.
      The most useful application of ICG angiography in this disease is the
      visualization of the seat and extension of the associated CNV In fact, it is well
      known that laser treatment of a pigment epithelial detachment at the pretear
      stage may facilitate the development of a tear of the RPE.

PMID- 10071157
TI  - Results of a combined procedure for cataract and glaucoma, using Crozafon-De
      Laage punch.
AB  - PURPOSE: Study the efficacy and safety of a combined procedure for coexisting
      cataract and open angle glaucoma. METHODS: Forty eyes of 33 patients with
      cataract and coexisting open angle glaucoma underwent phacoemulsification and
      trabeculectomy with Crozafon-De Laage punch. Data was recorded from the patients'
      hospital files and from a questionnaire answered by the patients' regular
      ophthalmologist. RESULTS: After a mean follow-up time of 20.6 months (SD 4.9,
      range 12-31) the mean reduction in number of anti glaucoma drugs was 1.2 (SD 1.2)
      from 2.6 (SD 0.71) before operation to 1.4 (SD 1.12) at last visit (p<0.001).
      During the same period the mean intraocular pressure (IOP) was reduced from 18.9
      (SD 5.2) mm Hg to 14.9 (SD 2.9) mm Hg (p<0.001). The mean visual acuity was
      preoperatively 0.24 (SD 0.21) and 0.60 (SD 0.35) at last visit. The reasons for
      visual acuity lower than 0.8 was mainly age related macular degeneration (AMD)
      and glaucoma. No serious sight threatening complications were seen. CONCLUSIONS:
      Combined phacoemulsification and trabeculectomy with Crozafon-De Laage punch is a
      safe and effective method for improving both visual acuity and control of
      intraocular pressure in coexistent cataract and open angle glaucoma.

PMID- 10071158
TI  - Panorama of orbital space-occupying lesions. The 24-year experience of a referral
      centre.
AB  - PURPOSE: The aim of this survey was to study the frequency and management of
      orbital lesions requiring incisional or excisional biopsy for diagnostic or
      therapeutic purposes. METHODS: A histopathological review of specimens from 300
      consecutive patients with space-occupying orbital lesions managed over a period
      of 24 years at a tertiary referral centre. RESULTS: The lesions could be
      attributed to 73 different entities with low-grade, non-Hodgkin lymphoma being
      the most common. More than half (54.3%) of lesions were neoplastic and malignant
      disease was present in 29.0% of patients. The majority of lesions were biopsied
      using the anterior transseptal or transconjunctival approach. CONCLUSION: Most
      orbital space-occupying lesions requiring biopsy are benign and easily
      accessible. However, the diversity of these rare lesions and complexity of
      management suggest that patient care is best provided by a team of experienced
      subspecialists at a designated orbital centre.

PMID- 10071159
TI  - Mortality and causes of mortality among cataract-extracted patients. A 10-year
      follow-up.
AB  - PURPOSE: The purpose of this study was to compare the mortality among patients
      undergoing intracapsular cataract extraction to the mortality in a gender-and age
      identical Danish reference population, and to compare the patients' primary
      causes of death to those in the general population. MATERIALS AND METHODS: We
      reviewed medical records of patients undergoing ICCE from January 1st 1984 to
      December 31st 1986 at the Department of Ophthalmology, Aalborg Hospital, Denmark.
      Information on the deaths of these patients was obtained from the Danish National
      Population Register. Information on mortality in Denmark was obtained from
      published statistics. RESULTS: We found an increased mortality among the patients
      with cataract with an SMR (standard mortality rate) of 1.12 (95% confidence
      interval 1.02-1.23). The slightly increased mortality was observed for both men
      and women and for all examined causes of death. CONCLUSION: The slightly
      increased mortality among patients with cataract may indicate a general
      deterioration of health for these patients.

PMID- 10071160
TI  - Working with glaucoma patients - prospects for "shared care".
AB  - PURPOSE: To investigate the prospects for "shared care" by evaluating to what
      extent ophthalmic nurses are involved in ophthalmic care decision tasks in the
      management of glaucoma patients, how well prepared the nurses feel they are for
      these tasks and their level of satisfaction in those tasks they actually are
      performing. METHODS: A questionnaire was sent to the ophthalmic nurses at 13 eye
      clinics in Sweden. The clinics were selected to represent different parts of
      Sweden as well as university clinics and smaller rural clinics. RESULTS: A
      difference was found between clinics regarding the number of tasks independently
      performed by the ophthalmic nurses and a significant correlation was found
      between level of participation and satisfaction (p=0.008). The nurses felt
      prepared for (61/62) and satisfied (58/62) when performing the glaucoma
      management tasks, and a high and very significant correlation (r=0.96, p= 0.0001)
      was found between the mean preparedness and satisfaction scores for each of the
      14 tasks. CONCLUSIONS: The findings in the study show that the ophthalmic nurses
      feel prepared for their tasks and regard their involvement in glaucoma care as
      subjectively satisfactory. These observations support the idea of "shared care"
      in glaucoma management.

PMID- 10071161
TI  - Optic nerve cysticercosis in the optic canal.
AB  - The authors present a first case of cysticercosis in the optic canal in a fifteen
      year-old female patient. Cysticercosis of the optic nerve is rare. A cyst in the
      optic canal, beneath the sheath of the optic nerve, has never been reported. The
      patient presented with rapidly diminishing vision in the left eye, headache and
      papillitis. A magnetic resonance imaging revealed a cystic lesion at the entrance
      of the optic canal. Surgery performed was a transcranial orbitotomy which
      included deroofing of the optic canal and removal of the cyst from under the
      sheath of the optic nerve. The cyst proved to be cysticercus histopathologically.
      The outcome was a remarkable visual recovery.

PMID- 10071162
TI  - Antibiotic-induced endotoxemia in a patient with endogenous endophthalmitis.
AB  - PURPOSE: The aim of the study is to describe a case of suspected endotoxin
      induced uveitis associated with septic endogenous endophthalmitis followed by
      antibiotic-induced endotoxemia. METHODS: The human leukocyte antigen (HLA) typing
      of peripheral leukocytes was studied by lymphocytotoxicity technique.
      Histological and immunohistochemical studies of paraffin embedded specimen were
      conducted. RESULTS: Findings of HLA typing revealed positive reaction for B 51,
      Cw 3, DR 8, DR 11, DQ 3. The vitreous body of an eviscerated eye was occupied by
      the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and
      Sudan black staining positive foamy cells, including melaniferous phagocytes,
      identified as CD 68 positive macrophage. CONCLUSION: It is suggested that
      antibiotic-induced endotoxemia of a patient with septic endogenous
      endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA
      and endotoxin activated macrophages may release cytokines, followed by fibrin
      formation and subsequent granuloma.

PMID- 10071163
TI  - Bilateral open-angle glaucoma.

PMID- 10071164
TI  - Transactions of the Swedish Society of Ophthalmology 1997. Annual Meeting,
      Sundsvall, August 27-30, 1997.

PMID- 10071165
TI  - Adult patients with "asymptomatic" and "compensated" hydrocephalus benefit from
      surgery.
AB  - OBJECTIVES: There exists no consensus regarding the appropriate treatment of the
      group of adult hydrocephalus patients often denoted as "arrested"/ "compensated",
      "asymptomatic" or "symptomatic congenital". Our case series describes the results
      of CSF diversion in these patients. MATERIAL AND METHODS: During the period of
      1984 to 1994, 23 consecutive adult patients with "asymptomatic" (n = 10),
      "compensated" (n = 7) and "symptomatic congenital" (n = 6) hydrocephalus were
      prospectively evaluated. All patients showed signs of motor or psychometric
      impairment, had indications of an infantile or childhood debut, and had
      previously been ignored. In 15 patients the ventricular enlargement was a
      coincidental finding. Seventeen patients underwent shunt surgery or endoscopic
      third ventriculostomy. RESULTS: All but one operated upon improved. Six patients
      declined surgery, but have been followed with 1 showing deterioration, the
      remaining being unchanged. CONCLUSION: In addition to patients with "symptomatic
      congenital" most adult "asymptomatic" and "arrested"/"compensated" hydrocephalus
      patients can benefit from surgery despite a considerable duration of disease.

PMID- 10071166
TI  - Correlation between sex hormones and magnetic resonance imaging lesions in
      multiple sclerosis.
AB  - OBJECTIVE: To determine if sex hormones play a role in the pathogenesis of
      multiple sclerosis (MS) by correlating serum estradiol and progesterone levels
      with gadolinium (Gd) enhancing lesions on magnetic resonance imaging (MRI) in MS.
      METHODS: Thirty patients with MS were studied with Gd enhanced brain MRI and
      simultaneous serum estradiol and progesterone levels either during the early
      follicular, late follicular or luteal phases of their menstrual cycle.
      Correlation between hormone levels and number of Gd enhancing lesions was
      determined. RESULTS: Patients with high estradiol and low progesterone levels had
      a significantly greater number of Gd enhancing lesions than those with low levels
      of both these hormones. Patients with a high estrogen to progesterone ratio had a
      significantly greater number of active MRI lesions than those with a low ratio.
      CONCLUSION: Estradiol and progesterone may influence disease activity in MS. If
      further studies confirm these results, it may be possible to develop therapy by
      altering levels of these hormones.

PMID- 10071167
TI  - A study of increased levels of soluble vascular cell adhesion molecule-1 (sVCAM
      1) in the cerebrospinal fluid of patients with multiple sclerosis and systemic
      lupus erythematosus.
AB  - The concentration of soluble vascular cell adhesion molecules (sVCAM-1) of serum
      and cerebrospinal fluid (CSF) was measured in clinically selected multiple
      sclerosis (MS) and systemic lupus erythematosus (SLE) patients, using an ELISA
      assay. The mean sVCAM-1 concentration in the serum of SLE patients was higher
      than normal. The mean CSF sVCAM-1 concentration was increased in the MS as in the
      SLE group. On analysis, the data suggests that there are some similarities in the
      immunological effects of these two different diseases of the central nervous
      system. A longitudinal analysis of the CSF is requested.

PMID- 10071168
TI  - Profile of non-compressive myelopathy in eastern India: a 2-year study.
AB  - Eighty-two patients with non-compressive myelopathy have been studied from July
      1994 to June 1996 in Bangur Institute of Neurology and S.S.K.M. Hospital,
      Calcutta, of which 48 patients were men and 34 patients were women. Presentation
      was acute in 40 patients (48.78%), subacute in 7 (8.53%), chronic in 27 (32.92%)
      and history of relapse and remission in 8 (9.75%) patients. Preceding as well as
      simultaneous fever was observed in 16 cases (19.5%); vaccination (anti-rabies) in
      1 case (1.21%); drug abuse in 1 case (1.21%); arthralgia-myalgia and rash in 2
      cases (2.42%) and history of electrocution in 2 cases (2.42%). Only pyramidal
      tract involvement was present in 24 cases (29.26%) and remaining 58 cases
      (70.73%) had pyramidal tract affection with other sites of involvement. CSF study
      carried out in 60 cases, revealed rise of protein in 31 (37.8%); oligoclonal band
      had been detected in 6 (7.31%), pleocytosis in 18 cases (21.95%) and increased
      IgG index greater than 6.66 in 2 cases (2.42%). CT myelogram done in 23 cases
      revealed no abnormality. MRI study carried out in 59 cases showed myelomalacia in
      1 (1.21%); demyelination plaque in 14 cases (17.07%); atrophy of cord in 3
      (3.65%); infarction of cord in 1 (1.21%) and in 40 cases (48.78%) no abnormality
      could be detected. Etiological diagnosis could be established in 59 (71.95%)
      cases such as transverse myelitis or myelopathy (post infectious) in 24 (29.26%);
      demyelination in 16 (19.51%); vascular and vasculitis in 3 (3.65%); toxic in 1
      (1.21%); physical (electrocution) in 2 cases (2.42%). In the remaining 23 cases
      (28.04%) no aetiological factors could be found.

PMID- 10071169
TI  - Early-occurrence of manual motor blocks in Parkinson's disease: a quantitative
      assessment.
AB  - OBJECTIVES: Quantitative analysis of internally-cued, repetitive motor
      performance in patients with Parkinson's disease (PD). MATERIAL AND METHODS:
      Computerized quantitative measurements of the frequency, duration and temporal
      profile of manual motor blocks (MMBs) during performance of a manual tapping
      task, in 39 patients with PD, as compared to 17 age-matched healthy controls.
      RESULTS: Performance of PD patients was markedly abnormal both quantitatively and
      qualitatively, as reflected by an increase (7.0% vs. 4.6%) in MMBs, and by their
      occurrence from onset of movement. The phenomenon was already observed in the
      early stages of the disease, and was also correlated with the occurrence of
      freezing of gait. A standard levodopa-carbidopa (125-12.5 mg) dose only partially
      affected this phenomenon. CONCLUSIONS: Augmented motor blocks in internally-cued
      performance should be recognized as a frequent, distinct and generalized feature
      of PD. Whereas the gait disorder is regarded as characteristic of the advanced
      stage of PD, our findings suggest that the basic defect in internal rhythm
      formation can be detected by sensitive measurement tools from the early stages of
      the disease. In addition, the methodology developed in this study to
      quantitatively measure manual motor blocks may be a useful tool for future
      development of therapeutic regimens for this debilitating aspect of motor
      dysfunction in PD.

PMID- 10071170
TI  - The role of essential fatty acids in chronic fatigue syndrome. A case-controlled
      study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled
      treatment study with high dose of EFA.
AB  - OBJECTIVE: To replicate the treatment study by Behan et al. (1990) using current
      research criteria for Chronic Fatigue Syndrome (CFS). METHOD: Fifty patients who
      fulfilled the Oxford Criteria for CFS were randomly allocated to treatment with
      either Efamol Marine or placebo for 3 months. They were seen monthly and
      completed a physical symptoms checklist and the Beck Inventory for Depression and
      reported if they were the same, better or worse at the end of the study. RESULTS:
      Symptoms generally improved with time but not significantly and there were no
      significant differences between the treatment and placebo groups. Pretreatment
      red-cell membrane (RBC) lipids of patients compared with age-and sex-matched
      normal controls showed no significant differences. DISCUSSION: The results of
      this study contrast sharply with the previous study where 85% of patients had a
      clinically significant improvement of symptoms with Efamol Marine over a 3-month
      treatment period.

PMID- 10071171
TI  - IgG index in acute idiopathic peripheral facial palsy.
AB  - OBJECTIVES: Etiologic hypotheses in acute idiopathic peripheral facial palsy
      (AIPFP) mostly point to an immunologic dysfunction, probably virus-induced.
      Though various immunologic abnormalities are reported, the problem is still
      unsolved. We investigated intrathecal immunoglobulin synthesis in AIPFP as a clue
      for central nervous system (CNS) immunopathology. MATERIAL AND METHODS: We
      studied IgG index in 24 patients with AIPFP, 10 with other neurological diseases
      (OND) and 17 with multiple sclerosis (MS). CSF and serum IgG were measured by
      radial immunodiffusion technique. IgG index is calculated according to Tibbling's
      formula. RESULTS: IgG indexes were abnormal in 6 patients with AIPFP, 3 with OND
      and 10 with MS patients. There was no statistical difference between AIPFP and
      OND groups, while marked difference existed between AIPFP and MS groups.
      CONCLUSION: Though IgG indexes were high in 25% of AIPFP patients, statistical
      analyses did not show any significance of this finding. Lack of a positive result
      might reflect non-existence of an extensive immunologic pathology within CNS,
      excluding a very limited one.

PMID- 10071172
TI  - Anticardiolipin antibodies: a study in cerebral venous thrombosis.
AB  - OBJECTIVES: Anticardiolipin antibodies (aCL) have been recognized as a marker for
      an increased risk of thrombosis. There are no documented reports from India on
      the prevalence of aCL in patients with cerebral venous thrombosis (CVT). Our
      study aimed at establishing the prevalence of these antibodies in patients with
      CVT and evaluating their clinical significance. SUBJECTS AND METHODS: Thirty-one
      patients with CVT diagnosed by angiography and/or cranial CT were investigated
      for the presence of aCL along with 31 age- and sex-matched normal controls. All
      subjects had no overt evidence of systemic lupus erythematosis or related
      autoimmune disorders. The titres of IgG and IgM type of aCL were estimated in the
      sera using a solid phase enzyme-linked immunosorbent assay. RESULTS:
      Anticardiolipin antibodies were detected in 22.6% of CVT patients compared to
      3.2% of normal controls (95% confidence interval (CI) 1.01 to 75.65). Five CVT
      patients had both IgG and IgM antibodies, and 2 had only IgG antibodies. The aCL
      positive group did not differ from the aCL-negative group with respect to the
      clinical characteristics and the demographic and risk factor profile. CONCLUSION:
      The findings suggest that anticardiolipin antibodies are a risk marker for
      cerebral venous thrombosis. Further studies on a larger group of patients are
      needed to establish the role of aCL in the pathogenesis of CVT.

PMID- 10071173
TI  - Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS
      syndrome.
AB  - We describe a clinically full-blown MELAS patient, who had an A3243G point
      mutation of mitochondrial DNA (mtDNA) in muscle and blood cells, and his family
      members. From the proband two muscle biopsies from the vastus lateralis muscle
      were analysed; one had typical ragged red fibers and focal cytochrome c oxidase
      deficiency and the other was completely normal. He also had a peripheral
      neuropathy confirmed by nerve conduction velocity and sural nerve biopsy studies.
      Axonal degeneration, relative loss of large myelinated fibers and paracrystalline
      inclusion bodies in the Schwann cells were noted. Intriguingly, the A3243G
      mutation of mtDNA was not found in the sural nerve biopsy. Therefore, we conclude
      that tissue mosaicism is present in the muscle fibers and that the mtDNA mutation
      may not be detected in the nerve involved as proved by pathology. We also suggest
      that the involvement of specific tissues in patients with mitochondrial diseases
      should be further determined by single fiber mtDNA analysis.

PMID- 10071174
TI  - Monocular involuntary eyelid closure.
AB  - OBJECTIVES: Monocular blepharospasm (MBLS) is precipitated by ipsilateral ocular
      pathology and becomes bilateral over time. Two patients are reported with
      monocular visual disturbance exhibiting monocular involuntary eyelid closure
      (MIEC), resembling MBLS. MATERIAL AND METHODS: A 31-year-old female with
      hyperthyroidism developed monocular polyopia with left eye vision on binocular
      fixation followed by ipsilateral visual extinction. Monocular vision was
      otherwise normal. A 57-year-old male with renal failure developed monocular
      blindness secondary to retinal hemorrhage. RESULTS: The first patient had
      anisocoria and proptosis. Brain magnetic resonance (MR) was normal. The second
      patient had involuntary movements of the left eye. Head computerized tomography
      (CT) was normal. Both patients exhibited MIEC of the eye with visual impairment
      that could be overcome voluntarily, but reappeared upon distraction. Neither of
      the two developed BLS in long-term follow-up. CONCLUSION: MIEC represents a
      complication of ipsilateral ocular pathology in the absence of other involuntary
      movements, apraxia of eyelid opening, or blepharospasm (BLS). MIEC needs to be
      distinguished from MBLS, since not all MBLS becomes bilateral.

PMID- 10071175
TI  - Does retinopathy in advanced type-I diabetes correlate to EEG patterns?

PMID- 10071176
TI  - The risk of acute suicidality in psychiatric inpatients increases with low plasma
      cholesterol.
AB  - Several studies suggest that the reduction of total cholesterol in blood by lipid
      lowering agents is accompanied by a decrease in the incidence of coronary heart
      disease, but not in total mortality. Likewise, epidemiological studies show that
      low total cholesterol concentrations appear to be associated with an increased
      risk of death from suicide and injuries. There is little information with respect
      to acute suicidality and cholesterol in psychiatric inpatients; therefore the aim
      of the present study was to examine exactly this relation between plasma
      cholesterol and acute suicidality. The study comprised 45 acutely suicidal
      psychiatric inpatients, 95 nonsuicidal inpatients with affective disorder, and 20
      healthy subjects. Psychopathological measures (Brief Psychiatric Rating Scale,
      Hamilton Depression Rating Scale, Beck's Suicide Intent Scale) were established
      in these patients as well as the plasma concentrations of cholesterol in patients
      and healthy subjects. The most important finding of this study is that the risk
      of acute suicidality decreases with increasing total cholesterol levels
      irrespective of age, gender, and nutritional status (i.e., body mass index).
      Comparison of total cholesterol levels between age- and sex-matched suicidal and
      nonsuicidal patients with affective disorder supports this observation: Despite
      the slightly higher body mass index, suicidal patients have significantly lower
      cholesterol levels than nonsuicidal patients. Our findings support the notion
      that acute suicidality is associated with low plasma cholesterol; this
      observation needs to be further studied in the context of a biological marker for
      suicide risk.

PMID- 10071177
TI  - Psychobiological differences between the aggression and psychoticism dimension.
AB  - Since blunted prolactin (PRL) and partly blunted cortisol responses have been
      reported for subjects with aggressive impulsive disorders as well as with
      psychopathy, it seemed worthwhile to try to separate the two types of aggression
      by their biological response. Since, furthermore, cortisol responses are more
      readily elicited by 5-HT1a challenges and prolactin responses by d-Fenfluramine
      or uptake inhibitors, these two types of drugs were used to answer the question
      if these hormone responses are suitable to differentiate between the two types of
      aggression. Two studies were conducted, one using 15 mg of d-Fenfluramine (d-Fen)
      in a double-blind placebo-controlled cross-over design in 40 males, the other
      using 10 mg of Ipsapirone (Ips) and placebo comparing 20 healthy males in each
      group. In each study subjects were divided according to above and below median
      aggression and psychoticism scores measured by questionnaire scales and combined
      into four groups defined by high and low aggression (Ag+/-) and psychoticism (P+/
      ) scores respectively. Analyses of covariance based an the two personality
      factors and the drug revealed for d-Fen cortisol nonresponse in P+ as opposed to
      P- and a blunted PRL response in Ag+ as opposed to Ag-. With Ips the cortisol
      response was positively related to Ag and not to P, while P+ showed a blunted PRL
      response not observed in Ag+. Joyfulness and well-being were also differentially
      affected by d-Fen in high and low P scorers, but not correlated to respective
      hormone responses. Different hypothalamic mechanism for eliciting the two hormone
      responses and differences in pre- and postsynaptic receptor sensitivities in the
      two personality dimensions are inferred from these findings.

PMID- 10071178
TI  - Stress and self-injurious behavior; hormonal and serotonergic parameters in
      mentally retarded subjects.
AB  - Self-injurious behavior (SIB) and stereotyped behavior (SB) are major challenges
      for professionals in the field of mental retardation. From animal experiments it
      has become obvious that these behavioral disturbances are not purposeless but may
      emerge secondary to restrictive environment and may serve de-arousing objectives.
      In mentally retarded subjects, several hypotheses have been formulated concerning
      the pathogenesis of SIB, particularly about the involvement of serotonin and beta
      endorphin, which are supported by beneficial treatment effects of the opiate
      antagonist naltrexone and serotonin modulating compounds, respectively. The
      present study was designed to investigate basal levels of stress-hormonal and
      serotonergic parameters as well as plasma levels of amino-acids and the beta
      carboline norharman in a group of 64 mentally retarded subjects with SB and/or
      SIB. Allocation to three different groups comprising 17 retarded controls, 26
      subjects with mainly SIB and 21 subjects with mainly SB, was originally performed
      using the scores on the factors Irritability, Stereotypic Behaviour and
      Hyperactivity of the Aberrant Behavioral Checklist. Because of the overlapping
      nature of the behavioral parameters, subjects were subsequently divided into
      three maximally contrasting groups, viz. predominantly SIB, predominantly SB and
      retarded controls, each comprising 11 subjects. With respect to beta-endorphin,
      no differences were found either between both the original and maximally
      contrasting groups or in comparison to nonretarded controls. As compared to
      retarded controls, a tendency to lower values for total cortisol and cortisol
      binding globulin appeared to be present in the SIB group, whereas in the SB group
      a tendency toward higher levels of the major serotonin metabolite 5-HIAA was
      found. In the contrasting SB group, a trend toward decreased total cortisol level
      was observed as compared to the retarded control group. In addition,
      significantly lower values for norharman and tryptophan were demonstrated in the
      total group of mentally retarded subjects as compared to non-retarded controls.
      The results of the present study, yielding co-existent disturbances in stress
      hormonal and monoaminergic mechanisms as well as in the metabolism of norharman,
      are in line with the hypothesis that mentally retarded subjects are at risk for
      the development of stress-related behavioral disorders such as SIB and SB.

PMID- 10071179
TI  - Assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug
      safety program: methods and first results for tricyclic antidepressants and SSRI.
AB  - The AMSP (Arzneimittelsicherheit in der Psychiatrie) study is a new program for
      continuous assessment of adverse drug reactions (ADR) in psychiatric inpatients
      under naturalistic conditions of routine clinical treatment. It is based on the
      preceding drug surveillance study AMUP (Arzneimitteluberwachung in der
      Psychiatrie). Currently, 29 hospitals are participating in the study. This paper
      reports on the methods of the AMSP study and the first findings on the
      comparative risks of tricyclic antidepressants (TCA) and selective serotonin
      reuptake inhibitors (SSRI) . Data assessment is restricted to "severe" ADR as
      defined in the study protocol. Drug use is estimated from reference day data.
      From 1993 to 1997, 896 cases of severe ADR were observed in 48,564 patients
      (1.84%). SSRI and the new substances mirtazapine and venlafaxine were
      increasingly used as antidepressants (AD), but TCA were still the most common AD
      in 1997 (52.1% of all AD patients). Similar rates of ADR were observed for SSRI
      and TCA (1.7% and 1.5%, respectively, for all cases, 0.9% and 1.0%, respectively,
      only for cases rated as probable). However, different types of ADR occurred with
      the two AD subgroups; whereas toxic delirium and increased liver enzymes were the
      most frequent ADR related toTCA, nondelirious psychic and neurologic ADR
      predominated with SSRI. The duration of inpatient treatment was considerably
      longer in patients who experienced an ADR due to TCA or SSRI than in those who
      did not. The AMSP study promises to contribute greatly to drug safety by
      providing the relative frequencies of severe ADR from a large-scale database and
      by improving our knowledge of ADR.

PMID- 10071180
TI  - Psychotropic drug prescription in a psychiatric university hospital.
AB  - A retrospective survey on drug prescription over a one-year period (1989) in 1083
      patients (48.3% of whom were male) hospitalized in a psychiatric university
      hospital in Switzerland and a 35-day prospective study (1992) on the prescription
      of "as needed" (prn) medication in a closed and an open ward were carried out.
      Their aim was to establish a basis for a monitoring of prescription habits and
      for pharmacoeconomic considerations. In the retrospective study, 48.3% of the
      patients were male. The mean duration of hospitalization of the patients was 47.0
      +/- 68.1 days (mean +/- s.d.). Only 11 out of the 1083 patients (1%) were without
      psychotropic medication. The mean (+/- SD) number of drugs/day the patients were
      prescribed was 4.6 +/- 2.8, including 3.2 +/- 1.7 psychotropic drugs. Patients
      suffering from schizophrenia (67 d) or from unipolar depression (67.4 d) were
      hospitalized for the longest periods. Antipsychotics (67.5% of the patients) were
      the most frequently prescribed psychotropic drugs, followed by anxiolytics
      (42.2%), antidepressants (28.3%), hypnotics (31.4%) and mood stabilizers (7.1%).
      Antiparkinsonian agents accounted for 4.6% of all prescriptions. Levomepromazine,
      haloperidol (30.9% of all patients) and clotiapine were the most often prescribed
      neuroleptics, and clozapine was administered to only 6.4% of all patients. Among
      the antidepressants, maprotiline (11.9% of all patients) was more frequently
      prescribed than the classical tricyclic antidepressant amitriptyline, while the
      only available SSRI fluvoxamine and MAO inhibitors were rarely used. The most
      frequently prescribed anxiolytics were clorazepate (28.2% of all patients),
      lorazepam, bromazepam, and prazepam. Among the hypnotic drugs, chloral hydrate
      (11.5%) was more frequently administered than the first-ranking benzodiazepine
      flunitrazepam (7.8%). In the prospective study, 97% and 77% of the patients (n =
      55) of the closed (n = 29) and of the open ward, respectively, were prescribed
      "as needed" (prn) drugs. However, only 71 and 80%, respectively, of these
      patients finally received the drug. The frequency of prescription was 34.9% for
      neuroleptics, 15.1% for anxiolytic drugs, 8.2% for non-benzodiazepine hypnotics
      and only 2.1% for benzodiazepine hypnotics. The most frequently prescribed
      neuroleptic drug was clotiapine (18% of all patients), but finally, only 29% of
      the prescribed doses were administered. Studies of this type are biased by the
      fact that local habits of prescription do not allow generalisation of the
      findings. Such surveys should be carried out more frequently and simultaneously
      in different centers. Critical comparisons could help to optimize treatment.

PMID- 10071181
TI  - A case of agitated catatonia.
AB  - Agitation is one of the diagnostic features of catatonia in the DSM IV
      classification, but permanent forms of agitated catatonia have occasionally been
      described. We report the case of a 43-year-old man who had already suffered from
      undifferentiated schizophrenia for 7 years, and in whom we diagnosed agitated
      catatonia. While our patient was being treated with a neuroleptic during a second
      episode of paranoia, a state of agitation was observed which persisted for a
      further 8 months. During this period, he was treated with several different
      neuroleptics and benzodiazepines, either alone or in association, without any
      improvement. No organic cause was found. He was then transferred to our
      electroconvulsive therapy (ECT) unit, with a diagnosis of schizophrenic agitation
      resistant to drug therapy. ECT was begun, and he was only given droperidol in
      case of agitation and alimemazine for insomnia, neither of which had any effect.
      In view of his persistent agitation without any purpose, echolalia and
      echopraxia, stereotyped movements with mannerisms and marked mimicking and
      grimacing, we diagnosed him as having agitated catatonia. After the fourth
      session of ECT, we decided to stop all treatment and gave him lorazepam at a dose
      of 12.5 mg daily. Twenty-four hours later, all symptoms of agitation had
      disappeared. In our opinion, permanent catatonic agitation is not rare. In our
      case, the neuroleptic treatment maintained and may even have worsened the
      symptomatology. Lorazepam can be used as a therapeutic test for this type of
      agitation, especially if it does not respond to neuroleptics. This also allows
      the patient to be sedated rapidly and effectively, thus preventing him from
      injuring himself further.

PMID- 10071182
TI  - Gynecomastia with risperidone-fluoxetine combination.
AB  - Gynecomastia (breast enlargement) is a side effect of neuroleptic antipsychotic
      drugs, related to prolactin elevation caused by dopamine D2 receptor blockade
      (Richelson, 1996). The atypical antipsychotic risperidone is less likely to cause
      gynecomastia at low doses (Casey, 1996). It can cause a dose-dependent increase
      in serum prolactin concentration (Peuskens, 1995), by blocking dopamine D2
      receptors (Richelson, 1996). I would like to describe a patient who did not have
      gynecomastia with risperidone at a dose of 3 mg/day, but had it when risperidone,
      at a dose of 0.5 mg/day, was combined with fluoxetine. A MEDLINE search failed to
      find any reports about such an interaction.

PMID- 10071183
TI  - Generalized tonic-clonic seizures following withdrawal of therapeutic dose of
      bromazepam.

PMID- 10071184
TI  - Borna disease in humans--speculations and controversies.

PMID- 10071185
TI  - Genotype and phenotype in patients with dihydropyrimidine dehydrogenase
      deficiency.
AB  - Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive
      disease characterised by thymine-uraciluria in homozygous deficient patients and
      has been associated with a variable clinical phenotype. In order to understand
      the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families
      presenting 22 patients with complete deficiency of DPD. In this group of
      patients, 7 different mutations have been identified, including 2 deletions [295
      298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense
      mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the
      various mutations among DPD patients has shown that the G-->A point mutation in
      the invariant splice donor site is by far the most common (52%), whereas the
      other six mutations are less frequently observed. A large phenotypic variability
      has been observed, with convulsive disorders, motor retardation and mental
      retardation being the most abundant manifestations. A clear correlation between
      the genotype and phenotype has not been established. An altered beta-alanine,
      uracil and thymine homeostasis might underlie the various clinical abnormalities
      encountered in patients with DPD deficiency.

PMID- 10071186
TI  - Werner syndrome lymphoblastoid cells are sensitive to camptothecin-induced
      apoptosis in S-phase.
AB  - Werner Syndrome (WRN) is an autosomal recessive disorder showing an endogenous
      mutator phenotype in combination with an elevated risk of predominantly
      mesenchymal cancer. The gene mutated in WRN patients codes for 3'-->5' DNA
      helicase and 3'-->5' exonuclease activities. We have found similar S-phase arrest
      in both WRN and control cells after treatment with the DNA-topoisomerase-I
      trapping drug camptothecin; this may be responsible for the drug-exposure-related
      growth inhibition seen in both cell types. A clearer phenotypic difference
      between WRN and control immortalized B-cell lines (LCLs) is obtained by examining
      cell death. The mechanism of camptothecin-induced cell death in WRN-deficient
      LCLs appears to be through apoptosis, a phenotype that strongly differentiates
      WRN-deficient from wild-type LCLs. We hypothesize that, in cells deficient for
      WRN function, a topoisomerase-I-DNA intermediate persists. Conflict with DNA
      replication may lead to apoptosis, increased mutation rates, and cancer in WRN.

PMID- 10071187
TI  - Disentangling the perturbational effects of amino acid substitutions in the DNA
      binding domain of p53.
AB  - The spectrum of somatic cancer-associated missense mutations in the human TP53
      gene was studied in order to assess the potential structural and functional
      importance of various intra-molecular properties associated with these
      substitutions. Relating the observed frequency of particular amino acid
      substitutions in the p53 DNA-binding domain to their expected frequency, as
      calculated from DNA sequence-dependent mutation rates, yielded estimates of their
      relative clinical observation likelihood (RCOL). Several biophysical properties
      were found to display significant covariation with RCOL values. Thus RCOL values
      were observed to decrease with increasing solvent accessibility of the
      substituted residue and with increasing distance from the p53 DNA-binding and
      Zn2+ -binding sites. The number of adverse steric interactions introduced by an
      amino acid replacement was found to be positively correlated with its RCOL value,
      irrespective of the magnitude of the interactions. A gain in hydrogen bond number
      was found to be only half as likely to come to clinical attention as mutations
      involving either a reduction or no change in hydrogen bond number. When the
      difference in potential energy between the wild-type and mutant DNA-binding
      domains was considered, RCOL values exhibited a minimum around changes of zero.
      Finally, classification of mutated residues in terms of their protein/solvent
      environment yielded, for somatic p53 mutations, RCOL values that resembled those
      previously determined for inherited mutations of human factor IX causing
      haemophilia B, suggesting that similar mechanisms may be responsible for the
      mutation-related perturbation of biological function in different protein folds.

PMID- 10071188
TI  - A trisomic germ cell line and precocious chromatid segregation leads to recurrent
      trisomy 21 conception.
AB  - A chromosomally normal 37-year-old woman was referred for preimplantation genetic
      diagnosis after having several conceptuses with trisomy 21. Segregation of
      chromosome 21 was assessed in unfertilised meiosis II oocytes and preimplantation
      embryos from PGD cycles using fluorescent in situ hybridisation (FISH). Of 7
      preimplantation embryos, 5 were chromosomally abnormal with 4 having trisomy 21
      and one being tetraploid. Of 4 oocytes, 3 had an abnormal chromosomal
      constitution with either an extra chromosome 21 or an extra chromatid 21. In one
      oocyte an extra chromatid 21 was detected in both the metaphase II complement and
      the first polar body providing the first direct evidence of a maternal trisomic
      germ cell line. Moreover, this result shows that the extra chromosome 21 can
      precociously divide into its two chromatids at the first meiotic division.

PMID- 10071189
TI  - A rapid automated SSCP multiplex capillary electrophoresis protocol that detects
      the two common mutations implicated in hereditary hemochromatosis (HH).
AB  - Currently two mutations in the HFE gene are known to be associated with the
      manifestation of the autosomal recessive disorder hereditary hemochromatosis
      (HH). A single-base mutation resulting in Cys282Tyr appears to have a causative
      role in the development of the disease, and a point mutation resulting in
      His63Asp may also be involved. Recent observations with a fully automated
      capillary electrophoresis (CE) system (ABI Prism 310) suggested that this
      instrument could be used for the precise identification of known mutations based
      on single-strand conformation polymorphism (SSCP). Two DNA fragments, each
      specific for one of the HFE mutation sites and labeled with a different
      fluorophor, were coamplified and without further manipulation simultaneously
      analyzed by CE-SSCP. Wild-type samples showed a mobility pattern that was clearly
      distinguishable from homozygous Cys282Tyr, homozygous His63Asp, or a compound
      heterozygous sample. To evaluate the reliability of this system for the detection
      of both mutations, 20 samples were analyzed blind. All genotypes, which were
      called automatically, were in concordance with those obtained by a previously
      validated restriction fragment length polymorphism method. Thus, SSCP in
      combination with CE provides a fast and precise research tool for the
      simultaneous identification of the two common mutations implicated in HH.

PMID- 10071190
TI  - A G to A transition at the last nucleotide of exon 6 of the gamma c gene (868G-
      >A) may result in either a splice or missense mutation in patients with X-linked
      severe combined immunodeficiency.
AB  - We report here that a defect of the interleukin common gamma subunit (gamma c) in
      X-linked severe combined immunodeficiency (XSCID) previously known as a missense
      mutation resulted instead in exon skipping in a Japanese XSCID patient. The
      phenotype of the patient was consistent with that of typical XSCID, and his
      Epstein-Barr virus-transformed B cells accordingly entirely lacked surface
      expression of gamma c . On analysis by the reverse transcription-polymerase chain
      reaction (RT-PCR), a single but small gamma c mRNA species was detected. Exon 6,
      which encodes the transmembrane domain of gamma c, was skipped in the mRNA. A G
      to A mutation was found at the last nucleotide of exon 6 of the gamma c gene
      (868G-->A). The predicted consequence of the exon skipping is a frameshift
      resulting in a premature stop codon, and the mutated gamma c presumably loses
      association with the cell membrane. In XSCID, this mutation (868G-->A) is known
      as a missense mutation that results in R285Q [corrected]. Previously reported
      patients with the same mutation apparently had no aberrant or alternative
      splicing but did have the R285Q [corrected] exchange. Similar mutations at the
      last nucleotide of an outskipped exon have been reported. However, such mutations
      do not always cause exon skipping. Analyses of RNA structural changes induced by
      the mutations supported the variability of consequences of the mutations. Taken
      together, our findings suggest that the 868G-->A mutation of the gamma c gene may
      affect gamma c transcripts differently, i.e., generating missense or exon
      skipping, in XSCID patients with the same mutation. Patient-specific variation in
      splicing thus appears to occur.

PMID- 10071191
TI  - Xp deletions associated with autism in three females.
AB  - We report eight females with small deletions of the short arm of the X
      chromosome, three of whom showed features of autism. Our results suggest that
      there may be a critical region for autism in females with Xp deletions between
      the pseudoautosomal boundary and DXS7103. We hypothesise that this effect might
      be due either to the loss of function of a specific gene within the deleted
      region or to functional nullisomy resulting from X inactivation of the normal X
      chromosome.

PMID- 10071192
TI  - A new assay for the analysis of X-chromosome inactivation based on methylation
      specific PCR.
AB  - The pattern of X-chromosome inactivation in females is currently evaluated by
      assays of differential methylation in the genes between the active and the
      inactive X chromosomes, with methylation-sensitive enzymes. We report a new assay
      in the human androgen receptor (HUMARA) locus involving a methylation-specific
      polymerase chain reaction (M-PCR) technique, independent of the use of
      restriction enzymes. The assay involves the chemical modification of DNA with
      sodium bisulfite and subsequent PCR. By using the assay with specific primers for
      the methylated allele, we obtained an X-inactivation pattern based on the ratio
      of the maternal inactive X to the paternal inactive X. These patterns were
      consistent with those obtained by conventional PCR assay at the same locus in 48
      female cases. We also obtained another X-inactivation pattern based on the ratio
      of the maternal active X to the paternal active X by using specific primers for
      the unmethylated allele. The latter pattern was complementary to the former
      pattern, and a combination of these patterns produced a reliable X-inactivation
      pattern. The assay revealed that 12 (11%) of the 105 normal females had non
      random inactivation patterns (>80:20 or <20:80). Four patients with an X;
      autosome translocation showed extremely non-random patterns, and these results
      were consistent with those obtained by previous molecular/cytogenetic studies. We
      conclude that M-PCR provides an accurate assay for X-inactivation and that it can
      be performed on various DNA samples unsuitable for restriction digestion.

PMID- 10071193
TI  - Fibroblast growth factor homologous factor 2 (FHF2): gene structure, expression
      and mapping to the Borjeson-Forssman-Lehmann syndrome region in Xq26 delineated
      by a duplication breakpoint in a BFLS-like patient.
AB  - Borjeson-Forssman-Lehmann syndrome (BFLS) is a syndromal X-linked mental
      retardation, which maps by linkage to the q26 region of the human X chromosome.
      We have identified a male patient with BFLS-like features and a duplication,
      46,Y,dup(X)(q26q28), inherited from his phenotypically normal mother.
      Fluorescence in situ hybridisation using yeast artificial chromosome clones from
      Xq26 localised the duplication breakpoint to an approximately 400-kb interval in
      the Xq26.3 region between DXS155 and DXS294/DXS730. Database searches and
      analysis of available genomic DNA sequence from the region revealed the presence
      of the fibroblast growth factor homologous factor gene, FHF2, within the
      duplication breakpoint interval. The gene structure of FHF2 was determined and
      two new exons were identified, including a new 5' end exon, 1B. FHF2 is a large
      gene extending over approximately 200 kb in Xq26.3 and is composed of at least
      seven exons. It shows tissue-specific alternative splicing and alternative
      transcription starts. Northern blot hybridisation showed highest expression in
      brain and skeletal muscle. The FHF2 gene localisation and tissue-specific
      expression pattern suggest it to be a candidate gene for familial cases of the
      BFLS syndrome and other syndromal and non-specific forms of X-linked mental
      retardation mapping to the region.

PMID- 10071194
TI  - Delineation of two distinct 6p deletion syndromes.
AB  - Deletions of the short arm of chromosome 6 are relatively rare, the main features
      being developmental delay, craniofacial malformations, hypotonia, and defects of
      the heart and kidney, with hydrocephalus and eye abnormalities occurring in some
      instances. We present the molecular cytogenetic investigation of six cases with
      6p deletions and two cases with unbalanced translocations resulting in monosomy
      of the distal part of 6p. The breakpoints of the deletions have been determined
      accurately by using 55 well-mapped probes and fluorescence in situ hybridization
      (FISH). The cases can be grouped into two distinct categories: interstitial
      deletions within the 6p22-p24 segment and terminal deletions within the 6p24-pter
      segment. Characteristics correlating with specific regions are: short neck,
      clinodactyly or syndactyly, brain, heart and kidney defects with deletions within
      6p23-p24; and corneal opacities/iris coloboma/Rieger anomaly, hypertelorism and
      deafness with deletions of 6p25. The two cases with unbalanced translocations
      presented with a Larsen-like syndrome including some characteristics of the 6p
      deletion syndrome, which can be explained by the deletion of 6p25. Such
      investigation of cytogenetic abnormalities of 6p using FISH techniques and a
      defined set of probes will allow a direct comparison of reported cases and enable
      more accurate diagnosis as well as prognosis in patients with 6p deletions.

PMID- 10071195
TI  - Refined mapping of the gene for autosomal dominant retinitis pigmentosa (RP17) on
      chromosome 17q22.
AB  - Linkage analysis was performed on a large Dutch family with autosomal dominant
      retinitis pigmentosa. Linkage was found to the RP17 locus on chromosome 17q22,
      which was previously described in two South African families by Bardien et al.
      (1995, 1997). Assuming that the disease phenotypes in these families are caused
      by the same gene, the RP17 critical region is refined to a 7.7-cM interval
      between markers D17S1607 and D17S948. Two positional candidate genes, the retina
      specific amine oxidase (RAO) gene (AOC2) and the cone transducin gamma gene
      (GNGT2), were excluded.

PMID- 10071196
TI  - Refined genetic and physical positioning of the gene for Doyne honeycomb retinal
      dystrophy (DHRD).
AB  - Doyne honeycomb retinal dystrophy (DHRD) is a late-onset autosomal dominant
      disorder that causes degeneration of the retina and can lead to blindness. We
      have previously assigned DHRD to a 5-cM region of chromosome 2p16 between marker
      loci D2S2739 and D2S378. Using sequence-tagged sites (STSs), expressed sequence
      tags (ESTs) and polymorphic markers within the DHRD region, we have identified 18
      yeast artificial chromosomes (YACs) encompassing the DHRD locus, spanning
      approximately 3 Mb. The YAC contig was constructed by STS content mapping of
      these YACs and incorporates 13 STSs, including four genes and six polymorphic
      marker loci. We also report the genetic mapping of two families with a dominant
      drusen phenotype to the DHRD locus, and genetic refinement of the disease locus
      to a critical interval flanked by microsatellite marker loci D2S2352 and D2S2251,
      a distance of approximately 700 kb. These studies exclude a number of candidate
      genes and provide a resource for construction of a transcriptional map of the
      region, as a prerequisite to identification of the DHRD disease-causing gene and
      genes for other diseases mapping in the region, such as Malattia leventinese and
      Carney complex.

PMID- 10071197
TI  - P57 (KIP2) polymorphisms and breast cancer risk.
AB  - A previous report in this journal has suggested that germline deletions in the
      proline-alanine-rich (PAPA-repeat) region of P57 (KIP2) are associated with
      increased risk of a variety of cancers, including breast cancer. We have analyzed
      the association of P57 PAPA-repeat deletion polymorphisms and breast cancer risk
      as part of a population-based case-control study of breast cancer. We have not
      observed an association between the presence of one or two copies of deletion
      polymorphisms in P57 and breast cancer risk (adjusted odds ratio: 1.1, 95%
      confidence interval: 0.6-2.0). Further investigation is necessary to determine
      the functional significance of P57 deletion polymorphisms and their potential
      relationship with disease.

PMID- 10071198
TI  - Genotyping single nucleotide polymorphisms by primer extension and high
      performance liquid chromatography.
AB  - We have investigated the possibility of genotyping single nucleotide
      polymorphisms (SNPs) by primer extension and high performance liquid
      chromatography (HPLC). Using three polymorphisms of current interest to our group
      (an A/G polymorphism in the proneurotensin gene and A/G and T/C polymorphisms in
      the 5HT2a receptor gene), we show that robust signal is obtained using this
      simple analytic method which has the added advantages that sample loading and
      analysis are essentially automated, analytic time is brief, and no further
      purification step after primer extension is required. We also show that all
      stages of the HPLC-primer extension genotyping can be multiplexed which, together
      with automation, suggests that this system may be suitable for linkage studies
      based upon emerging SNP maps.

PMID- 10071199
TI  - A large Alu-mediated deletion, identified by PCR, as the molecular basis for
      glycogen storage disease type II (GSDII).
AB  - Glycogen storage disease type II (GSDII) is an autosomal recessive disorder
      resulting from inherited deficiency of the enzyme lysosomal acid alpha
      glucosidase. Over 40 different mutations have been described but no large
      deletions have been previously identified. We now describe a homozygous large (9
      kb) deletion extending from IVS 15 to 4 kb downstream of the terminal exon (exon
      20), detected by polymerase chain reaction (PCR)-based methods. The deletion was
      initially suspected because of failure to amplify a contiguous group of exons by
      PCR. We hypothesized an Alu/Alu recombination, based on our prior demonstration
      by Southern blotting of Alu elements in the regions potentially flanking the
      deletion. Additional sequence analysis of genomic fragments confirmed the
      presence of Alu elements and allowed the design of flanking primers for PCR
      amplification. Amplification resulted in a smaller than normal fragment (0.7 vs.
      10 kb) in homozygosity in the proband and in heterozygosity in her parents.
      Cloning and sequencing of the smaller than normal 0.7-kb deletion fragment
      revealed an Alu/Alu deletion junction. In heterozygosity this deletion would not
      be detected by currently standard PCR mutation detection methods. Based on other
      Alu-mediated deletions, this deletion is likely to be recurrent and should be
      screened for in all non-consanguineous GSDII patients, particularly when only one
      mutation has been identified and none of the 12 single-nucleotide polymorphisms
      in the deleted region are heterozygous. These observations also suggest that
      initial characterization of genes at disease-causing loci should include a search
      for Alu and other repetitive elements to facilitate subsequent PCR-based mutation
      analysis.

PMID- 10071200
TI  - Mapping and genomic characterization of the gene encoding diacylglycerol kinase
      gamma (DAGK3): assessment of its role in dominant optic atrophy (OPA1).
AB  - The family of diacylglycerol kinases (DAGKs) is known to play an important role
      in signal transduction linked to phospholipid turnover. In the fruitfly
      Drosophila melanogaster, a human DAGK ortholog, DGK2, was shown to underlie the
      phenotype of the visual mutant retinal degeneration A (rdgA). Previously, the
      gene encoding a novel member of the human DAGK family, termed DAGK3, was cloned
      and demonstrated to be abundantly expressed in the human retina. Based on these
      findings we reasoned that DAGK3 might be an excellent candidate gene for a human
      eye disease. In the present study, we report the genomic organization of the
      human DAGK3 gene, which spans over 30 kb of genomic DNA interrupted by 23
      introns. In addition, we have mapped the gene locus by fluorescence in situ
      hybridization to 3q27-28, overlapping the chromosomal region known to contain the
      gene underlying dominant optic atrophy (OPA1), the most common form of hereditary
      atrophy of the optic nerve. Mutational analysis of the entire coding region of
      DAGK3 in 19 unrelated German OPA1 patients has not revealed any disease-causing
      mutations, therefore excluding DAGK3 as a major cause underlying OPA1.

PMID- 10071201
TI  - Characterization of a novel alpha-mannosidosis-causing mutation and its use in
      leukocyte genotyping after bone marrow transplantation.
AB  - Alpha-Mannosidosis is a lysosomal storage disorder caused by deficiency of
      lysosomal alpha-mannosidase (LAMAN). Major symptoms include mental retardation,
      skeletal changes and recurrent infections. Recently, a successful bone marrow
      transplantation (BMT) in an alpha-mannosidosis patient was reported. Here we show
      that this patient was homozygous for a novel mutation, a 1-bp insertion (1197
      1198insA) in exon 9 of the LAMAN gene. By using this mutation as a marker, we
      demonstrate that 1 year post-BMT, the LAMAN genotype of the patient's leukocytes
      was identical to that of the donor. This method of genotyping blood cells is a
      fast and accurate way to monitor the colonization of donor bone marrow cells.

PMID- 10071202
TI  - Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and
      anorectal malformations with sacral hypodevelopment.
AB  - Anorectal malformations (ARMs) are common congenital anomalies that account for
      1:4 digestive malformations. ARM patients show different degrees of sacral
      hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome
      (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A
      gene responsible for CS has recently been mapped in 7q36. Among the genes
      localized in this critical region, sonic hedgehog (SHH) was thought to represent
      a candidate gene for CS as well as for ARM with different levels of sacral
      hypodevelopment according to its role in the differentiation of midline mesoderm.
      By linkage analysis we confirmed the critical region in one large family with
      recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic
      ARM patients with sacral hypodevelopment allowed us to exclude its role in the
      pathogenesis of these disorders.

PMID- 10071203
TI  - A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12-->G)
      but no exon 3 mutations in the glycogen debranching enzyme gene in a homozygous
      patient with glycogen storage disease type IIIb.

PMID- 10071204
TI  - Organization of the 1.9-kb repeat unit RCE1 in the centromeric region of rice
      chromosomes.
AB  - This paper presents the first report on the structure of a 14-kb centromere
      sequence in a cereal genome that includes 1.9-kb direct repeats. The cereal
      centromeric sequence (CCS1) conserved in some Gramineae species contains a 17-bp
      motif similar to the CENP-B box, which serves as the binding site for the
      centromere-specific protein CENP-B in human. To isolate centromeric units from
      rice (Oryza sativa L.), we performed PCR using the CENP-B box-like sequences
      (CBLS) as primers. A 264-bp clone was amplified by this method, and called
      RCS1516. It appeared to be a novel member of the CCS1 family, sharing about 60%
      identity with the CCS1 sequences of other cereals. Then, a 14-kb genomic clone,
      lambda RCB11, carrying the RCS1516 sequence was isolated and sequenced. It was
      found to contain three copies of a 1.9-kb direct repeat, RCE1, separated by 5.1-
      and 1.7-kb. A 300-bp sequence at the 3' end of RCE1 is highly conserved in all
      three copies (>90%) and is almost identical to the RCS1516 sequence including the
      CBLS motif. The copy number of RCE1 was estimated to range from 10(2) to 10(3) in
      the haploid genome of rice. Cloned RCE1 units were used for fluorescent in situ
      hybridization (FISH) analysis, and signals were observed on almost every primary
      constriction of rice chromosomes. Thus it was concluded that RCE1 is a
      significant component of the rice centromere. The lambda RCB11 clone contained at
      least four A/T-rich regions, which are candidate for matrix attachment regions
      (MARs), in the sequences between the RCE1 repeats. Other elements that are
      homologous to the short centromeric repetitive sequences pSau3A9 and pRG5,
      detected in both sorghum and rice, were also found in the clone.

PMID- 10071205
TI  - Functional analysis of multiple AUG codons in the transcripts of the STA2
      glucoamylase gene from Saccharomyces cerevisiae.
AB  - A scanning ribosome will usually initiate translation as soon as it encounters
      the first favourable AUG codon and only a few eukaryotic transcripts have more
      complex arrangements. These relatively few complex transcripts are normally
      characterized by structural features such as multiple AUGs and significant
      secondary structure. However, the functional relevance of these features has
      rarely been established. We present here a study of the functional significance
      of the multiple AUGs in the leader of STA2 transcripts of the budding yeast
      Saccharomyces cerevisiae, and extrapolate, where applicable, these results to a
      co-regulated gene, MUC1. The STA2 gene (a representative member of the
      polymorphic STA1-3 gene family), encodes an extracellular glucoamylase, and is
      evolutionarily linked to, and transcriptionally co-regulated with, the MUC1 gene,
      which encodes a mucin-like protein essential for pseudohyphal/invasive growth and
      cell-adhesion in S. cerevisiae. Each of these genes contains a putative upstream
      ORF, while STA2 has two additional in-frame AUG codons 5' to the major cistron.
      We show that utilization of the alternative translational start-sites of STA2
      results in glucoamylases that differ at their N-termini, which are associated
      with differences in their localization patterns. Analysis of mutants revealed the
      presence of a putative secretion-enhancing signal that might prove to be relevant
      to the alternative targeting mechanism recently uncovered in S. cerevisiae. We
      show that a short up-stream ORF present in the leaders of STA1-3 and MUC1 is
      probably bypassed by a process of leaky scanning.

PMID- 10071206
TI  - The argininosuccinate lyase gene of Chlamydomonas reinhardtii: cloning of the
      cDNA and its characterization as a selectable shuttle marker.
AB  - We describe the cDNA sequence for ARG7, the gene that encodes argininosuccinate
      lyase--a selectable nuclear marker--in Chlamydomonas reinhardtii. The 5' end of
      the cDNA contains one more exon and the organisation of the mRNA is different
      from that predicted from the genomic sequence. When expressed under the control
      of the endogenous RbcS2 promoter, the 2.22-kb cDNA complements the arg7 mutation
      as well as the genomic DNA. A linear cDNA fragment lacking promoter sequences is
      also able to complement, suggesting that it could be used in promoter-trapping
      experiments. Despite the presence of a sequence encoding a potential chloroplast
      transit peptide in the cDNA the protein is not targeted to the chloroplast, nor
      can it complement the arg7 mutation when expressed there. By inserting a T7
      bacteriophage promoter into the plasmid, a version of the cDNA which is able to
      complement both the C. reinhardtii arg7 mutant and the Escherichia coli argH
      mutant has been created. This modified Arg7 cDNA provides two advantages over the
      genomic DNA currently in use for gene tagging: it is shorter (6.2 kb versus 11.9
      kb for pARG7.8phi3), and the selectable marker used in C. reinhardtii is the same
      as that used in E. coli, making plasmid rescue of the tag much more likely to
      succeed.

PMID- 10071207
TI  - Isolation and characterization of a purC(orf)QLF operon from Lactococcus
      [correction of Lactobacillus] lactis MG1614.
AB  - We have isolated genes encoding enzymes of the de novo purine nucleotide
      biosynthesis pathway from Lactococcus lactis MG1614 by colony hybridization using
      DIG-labeled DNA probes. The organization of the genes needed for the de novo
      biosynthesis of purine nucleotides in L. lactis differs from that found in other
      organisms. In L. lactis there is a gene cluster, which contains five out of the
      11 genes needed for the de novo biosynthesis of IMP, namely purC, orf, purQ, purL
      and purF. These genes were shown to be transcribed as a single transcription unit
      by Northern hybridization analysis. The 5' end of the transcript of the
      purC(orf)QLF operon was determined by primer extension analysis using
      fluorescently end-labeled probes. The purC(orf)QLF operon of L. lactis is
      transcribed in Escherichia coli, and the gene product of the purF gene, glutamine
      phosphoribosylpyrophosphate amidotransferase (glutamine PRPP ATase, EC 2.4.2.14),
      can functionally complement the E. coli purF mutant strain TX158. We also show
      that the promoter of the purC(orf)QLF operon is regulated in response to
      exogenously added purines.

PMID- 10071208
TI  - Identification of 1-aminocyclopropane-1-carboxylic acid synthase genes
      controlling the ethylene level of ripening fruit in Japanese pear (Pyrus
      pyrifolia Nakai).
AB  - The shelf life of Japanese pear fruit is determined by its level of ethylene
      production. Relatively high levels of ethylene reduce storage potential and fruit
      quality. We have identified RFLP markers tightly linked to the locus that
      determines the rate of ethylene evolution in ripening fruit of the Japanese pear.
      The study was carried out using sequences of two types of 1-aminocyclopropane-1
      carboxylic acid (ACC) synthase genes (PPACS1 and pPPACS2) and a ACC oxidase gene
      (PPAOX1) as probes on 35 Japanese pear cultivars expressing different levels of
      ethylene (0.0 to approximately 300 microl/kg fresh weight/h) in ripening fruit.
      When total DNA was digested with HindIII and probed with pPPACS1, we identified a
      band of 2.8 kb which was specific to cultivars having very high ethylene levels
      (> or = 10 microl/kg f.w./h) during fruit ripening. The probe pPPACS2 identified
      a band of 0.8 kb specific to cultivars with moderate ethylene levels (0.5
      microl/kg f.w./h-10 microl/kg f.w./h) during fruit ripening. The cultivars that
      produce high levels of ethylene possess at least one additional copy of pPPACS1
      and those producing moderate levels of ethylene have at least one additional copy
      of pPPACS2. These results suggest that RFLP analysis with different ACC synthase
      genes could be useful for predicting the maximum ethylene level during fruit
      ripening in Japanese pear.

PMID- 10071209
TI  - Genetic and physical analysis of a YAC contig spanning the fungal disease
      resistance locus Asc of tomato (Lycopersicon esculentum).
AB  - The Alternaria stem canker disease of tomato is caused by the necrotrophic fungal
      pathogen Alternaria alternata f. sp. lycopersici (AAL). The fungus produces AAL
      toxins that kill the plant tissue. Resistance to the fungus segregates as a
      single locus, called Asc, and has been genetically mapped on chromosome 3 of
      tomato. We describe here the establishment of a 1383-kb YAC contig covering the
      Asc locus and a series of plants selected for recombination events around the Asc
      locus. It was shown that the YAC contig corresponds to a genetic distance of at
      least 11.2 cM. Thus, the recombination rate in the Asc region is six times higher
      (123 kb/cM) than the average for the tomato genome. Furthermore, the Asc locus
      could be localised to a 91-kb fragment, thus paving the way for the cloning and
      identification of the Asc gene(s) by complementation.

PMID- 10071210
TI  - A "defeated" rice resistance gene acts as a QTL against a virulent strain of
      Xanthomonas oryzae pv. oryzae.
AB  - The genetic components responsible for qualitative and quantitative resistance of
      rice plants to three strains (CR4, CXO8, and CR6) of Xanthomonas oryzae pv.
      oryzae (Xoo) were investigated using a set of 315 recombinant inbred lines (RILs)
      from the cross Lemont (japonica) x Teqing (indica) and a complete linkage map
      with 182 well distributed RFLP markers. We mapped a major gene (Xa4) and ten
      quantitative trait loci (QTLs) which were largely responsible for segregation of
      the resistance phenotype in the RILs. The Teqing allele at the Xa4 locus, Xa4T,
      acted as a dominant resistance gene against CR4 and CXO8. The breakdown of Xa4T
      associated resistance mediated by the mutant allele at the avrXa4 locus in the
      virulent strain CR6 results from significant changes in both gene action (lose of
      dominance) and the magnitude of gene effect (approximately 50% reduction).
      Nevertheless, Xa4T still acted as a recessive QTL with a significant residual
      effect against CR6. The mutant alleles at the avrXa4 locus in CXO8 and CR6 that
      lead to a reduction in effect, or "breakdown", of Xa4T were apparently
      accompanied by corresponding penalties for their fitness. The quantitative
      component of resistance to Xoo in the RILs was largely due to a number of
      resistance QTLs. Most resistance QTLs mapped to genomic locations where major
      resistance genes and/or QTLs for resistance to Xoo, blast and sheath blight were
      identified in the same cross. Most QTLs showed consistent levels of resistance
      against all three Xoo strains. Our results suggest that a high level of durable
      resistance to Xoo may be achieved by the cumulative effects of multiple QTLs,
      including the residual effects of "defeated" major resistance genes.

PMID- 10071211
TI  - Identification of nuclear genes encoding mitochondrial proteins: isolation of a
      collection of D. melanogaster cDNAs homologous to sequences in the Human Gene
      Index database.
AB  - As a first step towards using cross-species comparison to complete the inventory
      of the nuclear genes that encode mitochondrial polypeptides, and ultimately to
      understand their function through systematic molecular and genetic analysis in a
      model organism of choice, we report here the characterization of 41 Drosophila
      melanogaster cDNAs. These cDNAs were isolated by screening an ovarian expression
      library with antibodies against mitochondrial proteins and identify 17 novel
      Drosophila genes. The deduced amino acid sequences encoded by the majority of
      these cDNAs turned out to show significant homology to mitochondrial proteins
      previously identified in other species. Among others, ORFs putatively encoding
      six different subunits of ATP synthase and three NADH:ubiquinone reductase
      subunits were detected. By in situ hybridization, all cDNAs were mapped to single
      bands on polytene chromosomes, thus identifying candidate Drosophila genes
      required for mitochondrial biogenesis and maintenance. A search of the Human Gene
      Index database made it possible in most cases to align the entire Drosophila
      coding sequence with a human consensus sequence, suggesting that the cDNAs
      originate from insect counterparts of expressed mammalian genes. Our experimental
      strategy represents an efficient approach to the identification and interspecies
      comparison of genes encoding products targeted to the mitochondrion.

PMID- 10071212
TI  - Non-LTR retrotransposons (LINEs) as ubiquitous components of plant genomes.
AB  - During the course of work aimed at isolating a rice gene from Oryza australiensis
      by PCR, the oligonucleotide primers used were found to generate a fragment that
      showed sequence homology to the endonuclease (EN) region of the maize non-LTR
      retrotransposon (LINE) Cin4. We carried out further PCRs using oligonucleotide
      primers that hybridized to these sequences, and found that they amplified several
      fragments, each with homology to the EN regions, from Oryza sativa cv. Nipponbare
      as well as O. australiensis. We mapped the approximate locations of two rice LINE
      homologues by screening clones in a YAC library made from a rice (O. sativa)
      genome, and found that each homologue was present in a low copy number apparently
      at nonspecific regions on rice chromosomes. We then carried out PCR using
      degenerate oligonucleotide primers which hybridized to the rice LINE homologues
      and Cin4 to ascertain whether LINE homologues are present in a variety of members
      of the plant kingdom, including angiosperms, gymnosperms, bracken, horsetail and
      liverwort. Cloning and nucleotide sequencing revealed that 53 clones obtained
      from 27 out of 33 plant species contained LINE homologues. In addition to these
      homologues, we identified four homologues with EN regions in the Arabidopsis
      thaliana genome by a computer search of databases. The nucleotide sequences of
      almost all the LINE homologues were greatly diverged, but the derived amino acid
      sequences were well conserved, and all contained glutamic acid and tyrosine
      residues at almost the same relative positions as in the the active site regions
      of AP (apurinic/apyrimidinic)-endonucleases. The EN regions in the LINE
      homologues from closely related plant species show a closer phylogenetic
      relationship, indicating that sequence divergence during vertical transmission
      has been a major influence upon the evolution of plant LINEs.

PMID- 10071213
TI  - Functional implications of genetic interactions between genes encoding small
      GTPases involved in vesicular transport in yeast.
AB  - Ras-related, guanine nucleotide-binding proteins of the Ypt/Rab family play a key
      role at defined steps in vesicular transport, both in yeast and in mammalian
      cells. In yeast, Ypt1p has an essential function late in endoplasmic reticulum
      (ER) to Golgi transport, and the redundant Ypt31/Ypt32 GTPases have been proposed
      to act in transport through and/or from the Golgi. Here we report that mutant
      alleles of YPT31 and YPT32, whose gene products have a reduced affinity for GTP,
      are able to suppress the dominant lethal phenotype of YPT1(N121I). Co-expression
      of YPT1(N121I) and the suppressor YPT31(N126I) allow essentially undisturbed
      secretory transport in the absence of the respective wild-type GTPases. Such
      mutant cells massively overaccumulate 60-100 nm vesicles and are heat sensitive.
      It appears likely that the mutant GTPases, which are defective in nucleotide
      binding, compete for the binding of common interacting protein(s). These and
      other genetic interactions between YPT1, YPT31/32, ARF1 and SEC4 described here
      strongly support the view that Ypt31p and Ypt32p have a central, Golgi-associated
      function in anterograde or retrograde transport.

PMID- 10071214
TI  - A specific member of the Cab multigene family can be efficiently targeted and
      disrupted in the moss Physcomitrella patens.
AB  - The analysis of phenotypic change resulting from gene disruption following
      homologous recombination provides a powerful technique for the study of gene
      function. This technique has so far been difficult to apply to plants because the
      frequency of gene disruption following transformation with constructs containing
      DNA homologous to genomic sequences is low (0.01 to 0.1%). It has recently been
      shown that high rates of gene disruption (up to 90%) can be achieved in the moss
      Physcomitrella patens using genomic sequences of unknown function. We have used
      this system to examine the specificity of gene disruption in Physcomitrella using
      a member of the Cab multigene family. We have employed the previously
      characterised Cab gene ZLAB1 and have isolated segments of 13 other closely
      related members of the Cab gene family. In the 199-bp stretch sequenced, the 13
      new members of the Cab family show an average of 8.5% divergence from the DNA
      sequence of ZLAB1. We observed 304 silent substitutions and 16 substitutions that
      lead to a change in the amino acid sequence of the protein. We cloned 1029 bp of
      the coding region of ZLAB1 (including 177 of the 199 bp with high homology to the
      13 new Cab genes) into a vector containing a selectable hygromycin resistance
      marker, and used this construct to transform P. patens. In three of nine stable
      transformants tested, the construct had inserted in, and disrupted, the ZLAB1
      gene. There was no discernible phenotype associated with the disruption. We have
      therefore shown that gene disruption is reproducible in P. patens and that the
      requirement for sequence homology appears to be stringent, therefore allowing the
      role of individual members of a gene family to be analysed in land plants for the
      first time.

PMID- 10071215
TI  - Growth retardation and neonatal lethality in mice with a homozygous deletion in
      the C-terminal domain of RNA polymerase II.
AB  - The C-terminal domain (CTD) of the largest subunit of RNA polymerase II consists
      of tandem repeats of the consensus heptapeptide YSPTSPS. Deletion studies in
      tissue culture cells have indicated that the CTD plays an essential role in
      transcription, although the nature of this essential function remains unclear.
      About half of the CTD can be deleted without affecting the viability of cells in
      tissue culture. Paradoxically, the dispensable CTD repeats are precisely
      conserved among all mammals whose CTD sequences are known. To determine whether
      the mammalian CTD is important in transcription during mouse development, we
      developed a gene targeting approach to introduce deletions into the CTD coding
      region of mouse embryonic stem (ES) cells. To maintain a functional Rpo2-1 gene,
      the neo marker in the targeting vector was positioned outside of the Rpo2-1
      transcribed region, 1.2 kb from the site of the CTD deletion. G418-resistant
      clones were screened for co-integration of the CTD deletion, and the resulting ES
      lines were used to create germline chimeric mice. Stable heterozygous lines were
      established and mated to produce animals homozygous for the CTD deletion. We show
      here that mice homozygous for a deletion of thirteen of the 52 heptapeptide
      repeats are smaller than wild-type littermates and have a high rate of neonatal
      lethality. Surviving adults, although small, appear morphologically normal and
      are fertile. This result suggests that the CTD plays a role in regulating growth
      during mammalian development. The gene targeting approach described here should
      be useful for making further deletions in the CTD and may be of general
      applicability where it is desirable to engineer specific mutations in the
      germline of mice.

PMID- 10071216
TI  - Isolation, characterization and disruption of the areA nitrogen regulatory gene
      of Gibberella fujikuroi.
AB  - The gene areA-GF, a homologue of the major nitrogen regulatory genes nit-2, areA,
      nre and NUT1 of Neurospora crassa, Aspergillus nidulans, Penicillium chrysogenum
      and Magnaporthe grisea, respectively, was cloned from the gibberellin (GA)
      producing rice pathogen Gibberella fujikuroi. areA-GF encodes a protein of 972
      amino acid residues which contains a single putative zinc finger DNA-binding
      domain that is at least 98% identical to the zinc finger domains of the
      homologous fungal proteins. The areA-GF gene has been shown to be functional in
      N. crassa by heterologous complementation of a RIP induced nit-2 mutant. The
      transformation rate was nearly as high as in a homologous complementation
      control. Transformants were able to utilize nitrate and expressed a normally
      regulated nitrate reductase activity. To generate areA-GF- mutants, gene
      replacement experiments were performed using a linearized replacement vector
      carrying the hygromycin B phosphotransferase (hph) gene. The replacement of the
      zinc finger by the hygromycin cassette resulted in transformants which were
      unable to utilize nitrogen sources other than ammonium and glutamine, and gave
      significantly reduced gibberellin production yields. Complementation of such a
      mutant with the wild-type gene led to the full recovery of gibberellin
      production.

PMID- 10071217
TI  - T-DNA from Agrobacterium tumefaciens as an efficient tool for gene targeting in
      Kluyveromyces lactis.
AB  - The soil bacterium Agrobacterium tumefaciens can transfer a part of its tumour
      inducing (Ti) plasmid, the T-DNA, to plant cells. The virulence (vir) genes, also
      located on the Ti plasmid, encode proteins involved in the transport of T-DNA
      into the plant cell. Once in the plant nucleus, T-DNA is able to integrate into
      the plant genome by an illegitimate recombination mechanism. The host range of A.
      tumefaciens is not restricted to plant species. A. tumefaciens is also able to
      transfer T-DNA to the yeast Saccharomyces cerevisiae. In this paper we
      demonstrate transfer of T-DNA from A. tumefaciens to the yeast Kluyveromyces
      lactis. Furthermore, we found that T-DNA serves as an ideal substrate for gene
      targeting in K. lactis. We have studied the efficiency of gene targeting at the
      K. lactis TRP1 locus using either direct DNA transfer (electroporation) or T-DNA
      transfer from Agrobacterium. We found that gene targeting using T-DNA was at
      least ten times more efficient than using linear double-stranded DNA introduced
      by electroporation. Therefore, the outcome of gene targeting experiments in some
      organisms may depend strongly upon the DNA substrate used.

PMID- 10071218
TI  - Antibody analysis of the localisation, expression and stability of HlyD, the MFP
      component of the E. coli haemolysin translocator.
AB  - HlyD has a single transmembrane domain (residues 59-80) and a large periplasmic
      domain, and is essential for the secretion of haemolysin from Escherichia coli.
      Using an antibody raised against HlyD, the protein was localised to the cell
      envelope by immunofluorescence and to the cytoplasmic membrane by sucrose
      gradient analysis. We have examined the stability of this protein in the presence
      and absence of other putative components of the translocator, HlyB and TolC. HlyD
      is normally highly stable but in the absence of TolC, the steady-state level of
      HlyD is greatly reduced and the protein has a half-life at 37 degrees C of 36
      min. In the absence of HlyB, HlyD is also unstable and specific degradation
      products are detected, which co-fractionate with the inner membrane, indicating
      in this case limited cleavage at specific sites. However, the effect of removing
      both HlyB and TolC is not additive. On the contrary, in the absence of both HlyB
      and TolC the half-life of HlyD is approximately 110 min. This result shows that
      in the presence of HlyB removal of TolC renders HlyD more unstable than it is in
      the absence of both HlyB and TolC. This suggests that the presence of HlyB
      induces a structural change in HlyD. In addition, HlyB itself appears to be less
      stable in the absence of HlyD. These results are consistent with an interaction
      between HlyD/TolC and HlyB/HlyD. A derivative of HlyD, HlyD22, lacking the 40 N
      terminal residues of HlyD assembles into the inner membrane displaying the same
      stability with and without HlyB as wild type HlyD does. This N-terminal region
      therefore appears to play no role in stable localisation but is involved in
      secretion, since HlyD22 is completely secretion defective. Modification of the C
      terminus on the other hand completely destabilised the molecule and HlyD was not
      detectable in the envelope. Secretion of active haemolysin is limited to a brief
      period during mid to late exponential phase. In contrast, HlyD is apparently
      synthesised constitutively throughout the growth phase, demonstrating that the
      production of this component of the translocator is not the limiting factor for
      growth phase-dependent secretion.

PMID- 10071219
TI  - Evidence for an ergot alkaloid gene cluster in Claviceps purpurea.
AB  - A gene (cpd1) coding for the dimethylallyltryptophan synthase (DMATS) that
      catalyzes the first specific step in the biosynthesis of ergot alkaloids, was
      cloned from a strain of Claviceps purpurea that produces alkaloids in axenic
      culture. The derived gene product (CPD1) shows only 70% similarity to the
      corresponding gene previously isolated from Claviceps strain ATCC 26245, which is
      likely to be an isolate of C. fusiformis. Therefore, the related cpd1 most
      probably represents the first C. purpurea gene coding for an enzymatic step of
      the alkaloid biosynthetic pathway to be cloned. Analysis of the 3'-flanking
      region of cpd1 revealed a second, closely linked ergot alkaloid biosynthetic gene
      named cpps1, which codes for a 356-kDa polypeptide showing significant similarity
      to fungal modular peptide synthetases. The protein contains three amino acid
      activating modules, and in the second module a sequence is found which matches
      that of an internal peptide (17 amino acids in length) obtained from a tryptic
      digest of lysergyl peptide synthetase 1 (LPS1) of C. purpurea, thus confirming
      that cpps1 encodes LPS1. LPS1 activates the three amino acids of the peptide
      portion of ergot peptide alkaloids during D-lysergyl peptide assembly. Chromosome
      walking revealed the presence of additional genes upstream of cpd1 which are
      probably also involved in ergot alkaloid biosynthesis: cpox1 probably codes for
      an FAD-dependent oxidoreductase (which could represent the chanoclavine cyclase),
      and a second putative oxidoreductase gene, cpox2, is closely linked to it in
      inverse orientation. RT-PCR experiments confirm that all four genes are expressed
      under conditions of peptide alkaloid biosynthesis. These results strongly suggest
      that at least some genes of ergot alkaloid biosynthesis in C. purpurea are
      clustered, opening the way for a detailed molecular genetic analysis of the
      pathway.

PMID- 10071220
TI  - Mutations in the predicted aspartyl tRNA synthetase of Drosophila are lethal and
      function as dosage-sensitive maternal modifiers of the sex determination gene Sex
      lethal.
AB  - Stable activation of the Drosophila sex determination gene Sex-lethal in the
      female embryo is a multistep process. Early in embryogenesis Sex-lethal is
      regulated at the level of transcription, and then later in embryogenesis Sex
      lethal regulation switches to an autoregulatory RNA splicing mechanism. Previous
      studies have shown that successful activation of Sxl requires both maternally and
      zygotically provided gene products, many of which are essential for viability and
      have other, non-sex specific functions. Using a screen for dosage-sensitive
      modifiers we identified a new maternally expressed gene, l(2)49Db, as a likely
      participant in Sxl activation. We show that the establishment of the Sxl
      autoregulatory splicing loop, but not the earlier steps in Sxl activation, is
      sensitive to the maternal dosage of l(2)49Db. We further demonstrate that
      l(2)49Db encodes an aspartyl tRNA synthetase. Finally we present evidence that
      this effect is indirect, by demonstrating that mutations in tryptophanyl tRNA
      synthetase are also dosage-sensitive maternal modifiers of Sex-lethal. These data
      suggest that stable activation of Sex-lethal in the embryo may be particularly
      sensitive to perturbation of the translational machinery.

PMID- 10071221
TI  - Trifluoroleucine resistance and regulation of alpha-isopropyl malate synthase in
      Saccharomyces cerevisiae.
AB  - Seven spontaneous Saccharomyces cerevisiae mutants that express dominant
      resistance to 5,5,5-trifluoro-DL-leucine have been characterised at the molecular
      level. The gene responsible for the resistance was cloned from one of the mutants
      (FSC2.4). Determination of its nucleotide sequence showed that it was an allele
      of LEU4 (LEU4-1), the gene that encodes alpha-isopropyl malate synthase I (alpha
      IPM synthase I), and that the mutation involved a codon deletion localised close
      to the 3' end of the LEU4 ORF. Six different point mutations--four transitions
      and two transversions--were found in the remaining mutants. Alpha-IPM synthase
      activity was found to be insensitive to feedback inhibition by leucine in five of
      the strains. In the other two the enzyme was resistant to Zn2+-mediated
      inactivation by Coenzyme A, a previously postulated control mechanism in energy
      metabolism; as far as we know, this represents the first direct in vivo evidence
      for this mechanism. The seven mutations define a region, the R-region, involved
      in both leucine feedback inhibition and in Zn2+-mediated inactivation by CoA.
      Deletion experiments involving the R-region showed that it is also necessary for
      enzyme activity.

PMID- 10071222
TI  - Mutations in the Schizosaccharomyces pombe heat shock factor that differentially
      affect responses to heat and cadmium stress.
AB  - Heat shock factor (hsf) is the transcriptional activator that governs the
      transcriptional response of eukaryotic cells to stressful conditions. The
      structure and regulation of hsf is highly conserved. We describe deletion
      mutations in hsf+ that alter the ability of Schizosaccharomyces pombe to respond
      to different stressful conditions. One mutation causes increased sensitivity to
      cadmium while maintaining near normal sensitivity to heat stress, while another
      mutation confers increased sensitivity to heat stress but retains normal
      sensitivity to cadmium. Despite the differential sensitivity of these two strains
      to cadmium and heat stress, the mutant hsf proteins in each strain were activated
      by both cadmium and heat. However, we found that these mutations differentially
      affected the ability of hsf to activate different promoters: one mutated hsf
      activated the ssp1+ gene better than the wis2+ gene following either stress,
      while the other mutated hsf activated wis2+ better than ssp1+. We propose that
      the differential ability of strains that contain these mutant hsfs to survive
      cadmium and heat stress is not caused by differences in activation of hsf, but is
      caused instead by differential abilities of the mutant hsfs to activate the
      appropriate sets of genes needed for survival.

PMID- 10071223
TI  - A mutational study of the ArcA-P binding sequences in the aldA promoter of
      Escherichia coli.
AB  - The aldA gene (encoding aldehyde dehydrogenase) of Escherichia coli is
      anaerobically repressed by ArcA-P, the phosphorylated response regulator of the
      ArcB/A two-component signal transduction system. The promoter region of aldA
      contains two 10-bp sequences (5'-TGTTAATTAA-3') that perfectly match the proposed
      ArcA-P binding consensus (5'-[A/T]GTTAATTA[A/T]-3'). One consensus sequence is on
      the coding strand (-13 to -4 from the transcriptional start point), whereas the
      other is on the template strand (position -2 to -11). In this study we used the
      aldA promoter to test the validity of the proposed consensus sequence. DNase I
      protection experiments confirmed the 10-bp sequence to be a strong ArcA-P binding
      site. Alteration of the wild-type sequence from 5'-TGTTAATTAAC-3' to 5'
      TCTTAATTAAG-3' or 5'-TATTAATTAAT-3' by site-directed mutagenesis markedly
      decreased the in vitro affinity of the promoter region for ArcA-P, and abolished
      the anaerobic repression of mutant att lambda::phi (aldA'-lacZ) transcriptional
      reporter constructs. Both the in vitro and in vivo results therefore support the
      proposed consensus sequence.

PMID- 10071224
TI  - A Schizosaccharomyces pombe gene, ksg1, that shows structural homology to the
      human phosphoinositide-dependent protein kinase PDK1, is essential for growth,
      mating and sporulation.
AB  - Fission yeast (Schizosaccharomyces pombe) requires inositol for growth, mating
      and sporulation. To define putative genes that are involved in the processing and
      transduction of the inositol signal, mutants that are temperature sensitive for
      growth and sporulation were selected on a medium containing non-limiting amounts
      of inositol. Two such mutants (ksg1-208 and ksg1-358) were analyzed, which are
      impaired in mating and sporulation at 30 degrees C and undergo growth arrest in
      the G2 phase of the cell cycle at 35 degrees C. The ksg1 gene was isolated by
      functional complementation. It maps on the left arm of chromosome II and encodes
      a putative 592-amino acid protein which exhibits good structural homology to a
      human 3-phosphoinositide-dependent protein kinase (PDK1) and its rat and
      Drosophila homologues. The two mutants have the same substitution at amino acid
      position 159: a glycine residue is replaced by glutamic acid. Deletion of the
      gene is lethal for haploid cells. We propose that ksg1 is involved in one or
      several phosphoinositide signalling processes that are responsible for control of
      the life cycle.

PMID- 10071225
TI  - Towards rice genome scanning by map-based AFLP fingerprinting.
AB  - Map-based DNA fingerprinting with AFLP markers provides a fast method for
      scanning the rice genome. Three hundred AFLP markers identified with ten primer
      combinations were mapped in two rice populations. The genetic maps were aligned
      and almost full coverage of the rice genome was obtained. The transferability of
      AFLP markers between indica x japonica and indica x indica crosses was tested.
      The chromosomes were divided into DNA Fingerprint Linkage Blocks (DFLBs) defined
      by specific AFLP markers. Using these blocks, the degree of similarity or
      divergence within specific chromosome regions was calculated for nine varieties.
      Applications of map-based fingerprinting for biodiversity studies and maker
      assisted selection are discussed.

PMID- 10071226
TI  - One-to-one correspondence between the two genetic units and the tandemly
      duplicated transcriptional units of the polyhomeotic locus of Drosophila.
AB  - polyhomeotic (ph) is a complex locus in Drosophila defined by two genetic units.
      Two mutational events are necessary to obtain the null lethal phenotype.
      Molecular analysis has shown that the ph locus contains two transcriptional units
      coding for two very similar proteins. Although a strong argument in favor of a
      strict correlation between the genetic and molecular units can be constructed,
      there is no direct evidence for the hypothesis. Here, we show for all cases with
      detectable molecular defects that X-ray-induced generation of an amorphic allele
      from a pre-existing X-ray-induced hypomorphic allele with a lesion limited to one
      unit invariably involves a rearrangement in the other unit. This result proves
      that each genetic unit corresponds to one transcription unit.

PMID- 10071227
TI  - A putative sigma factor from Streptomyces sp. strain A21 can activate the
      expression of the cryptic operon bgl in Escherichia coli K-12.
AB  - Streptomyces sp A21 is a cellulolytic strain isolated from soil which was
      assigned to the genus Streptomyces on the basis of distinctive morphological
      features. A genomic library of A21 DNA has been constructed and transformed into
      Escherichia coli K-12 using a high-copy-number vector. One of the recombinant
      plasmids activates the cryptic bgl operon when inserted into appropriate strains.
      The complete sequence of the 1629-bp A21 DNA fragment has been determined. The
      analysis revealed the presence of an ORF whose putative product shows a high
      degree of similarity to RNA polymerase sigma factors; we therefore designated the
      gene psfS (Putative sigma factor, Streptomyces). Mapping of the 5' terminus of
      transcript by primer extension indicated that PsfS induces transcription
      initiation within the bgl promoter-silencer region.

PMID- 10071228
TI  - Consistency achieved by 23 European pathologists from 12 countries in diagnosing
      breast disease and reporting prognostic features of carcinomas. European
      Commission Working Group on Breast Screening Pathology.
AB  - A detailed analysis of the consistency with which pathologists from 12 different
      European countries diagnose and classify breast disease was undertaken as part of
      the quality assurance programme of the European Breast Screening Pilot Network
      funded by the Europe against Cancer Programme. Altogether 107 cases were examined
      by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories
      were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH)
      0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was
      the majority diagnosis in only 2 cases but was diagnosed by at least 2
      participants in another 14, in 9 of which the majority diagnosis was benign
      (explaining the relatively low kappa for this category). DCIS in 4 (all low
      nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The
      histological features of these cases were extremely variable; although one
      feature that nearly all shared was the presence of cells with small, uniform,
      hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis
      was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three
      categories and 0.46 when only two (high and other) were used. When ADH was
      included with low nuclear grade DCIS there was only a slight improvement in
      kappa. Size measurement of DCIS was less consistent than that of invasive
      carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of
      the majority being 100% in 49. The remainder were either special subtypes
      (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible
      microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa,
      0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of
      grading using the Nottingham method was moderate (kappa=0.53) and consistency of
      diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for
      consistency to improve from one round to the next, suggesting that further
      improvements are unlikely without changes in guidelines or methodology.

PMID- 10071229
TI  - Human endogenous retrovirus (HERV)-K transcripts in gonadoblastomas and
      gonadoblastoma-derived germ cell tumours.
AB  - Gonadoblastomas are rare tumours of abnormal or dysgenetic gonads, often
      transforming to invasive seminomatous and nonseminomatous germ cell tumours
      (GCT). Because of the intimate association of noninvasive and invasive lesions,
      gonadoblastoma may provide clues as to the molecular pathogenesis of GCT. We
      studied the expression of the human endogenous retrovirus (HERV)-K gag gene in
      eight gonadoblastomas arising in phenotypically female patients, including two
      newborn girls. We also studied testicular biopsies with immature Sertoli cell
      nodules harbouring neoplastic germ cells, a lesion with morphological resemblance
      to gonadoblastoma. In five gonadoblastomas, invasive seminoma/dysgerminoma was
      noted, in two cases with formation of additional GCT components. HERV-K gag
      transcripts were found with moderate levels in gonocytes of all gonadoblastomas
      and in neoplastic germ cells in testicular Sertoli cell nodules. All invasive GCT
      except for teratomas displayed HERV-K transcripts. Thus, expression of HERV-K is
      induced during fetal or embryonal development and precedes invasive GCT
      formation. Although the specific role of HERV-K expression remains unknown, the
      findings place HERV-K expression in an appropriate time frame for it to have a
      role in the molecular pathogenesis of GCT and suggest a precursor-invasive tumour
      relationship for ovarian GCT equivalent to the more common carcinoma in situ of
      the testis and testicular GCT.

PMID- 10071230
TI  - The role of the Epstein-Barr virus in the oncogenesis of EBV(+) gastric
      carcinomas.
AB  - Five hundred and thirteen cases of gastric carcinoma were investigated for the
      presence of viral RNA, and the clinico-pathological data, geno-type, BamHIF
      restriction fragment polymorphism (RFLP) and specific LMP-1 30 bp gene deletion
      were also examined. EBVs detected in lymphocytes in 20 normal gastric mucosa, 7
      lymphoma cell lines (LCLs) maintained in severe combined immunodeficiency (SCID)
      mice and 18 non-Hodgkin's lymphomas were compared with those in the gastric
      carcinoma cases. Thirty-three cases (6.4%) were demonstrated to be positive for
      EBV by means of EBER-1 RNA in situ hybridization. Clinico-pathological data
      showed no statistically significant difference in histological grading, location
      of cancer and status of vessel and lymphatic invasion between the EBV-positive
      and -negative groups, although the former significantly predominated in the
      submucosal invasion group (submucosal vs mucosal P=0.021; submucosal vs advanced
      cancer P=0.033). Some of these data were different from corresponding data in
      earlier reports. In cases that were evaluated by molecular biology, type A, wild
      type F and LMP-1 gene deletion predominated except one in 21 informative cases,
      one in 24 and two in 16, respectively. EBVs detected in lymphocytes in normal
      gastric mucosa, LCLs in SCID mice and non-Hodgkin's lymphoma were also
      predominantly affected by type A, wild-type F and LMP-1 gene deletion with few
      exceptions. The results indicate a lack of genetic differences among EBVs in
      gastric carcinoma, normal population, LCLs of SCID mice and non-Hodgkin
      lymphomas. Some EBV infections in gastric carcinomas may be transient, especially
      in the submucosal invasion group.

PMID- 10071231
TI  - P16/MTS1 and pRB expression in endometrial carcinomas.
AB  - p16MTS1/CDKN1 and the retinoblastoma protein Rb are both involved in negative
      regulation of G1/S progression in the mammalian cell cycle. Inactivation of one
      of these tumour suppressor genes is involved in many malignant tumours, and in
      some studies a negative correlation of p16 and Rb expression has been found. In
      order to study this interaction in endometrial carcinogenesis, we investigated 36
      endometrial carcinomas, 11 cases of hyperplasia, 23 normal endometrial samples,
      and two uterine carcinoma cell lines by immunohistochemistry or RT-PCR. Rb was
      expressed in normal endometrial epithelium, hyperplasia, cell lines, and most
      carcinomas; negative immunostaining was only detected in 1 of 36 tumours. In
      contrast, p16 expression was weak in normal endometrium and increased in most
      cases of hyperplasia, but negative or minimally positive in 74% of the carcinomas
      and the Hec1B adenocarcinoma cell line, and there was no significant association
      with Rb immunostaining. Strikingly high p16 expression was found in foci of
      squamous metaplasia within hyperplastic or carcinomatous tissue. Deletion and
      mutation analysis of the p16 gene was performed in DNA from microdissected tumour
      samples and cell lines. No p16 deletion was found, and mutations were detected in
      only one tumour sample and Skut1B uterine mixed mesodermal tumour cells. Our data
      indicate that in spite of low or absent p16 expression, genetic alterations of
      the p16 and Rb tumour suppressor genes are rare in endometrial carcinogenesis.

PMID- 10071232
TI  - Immunohistochemical localization of alpha- and betaA-subunits of inhibin/activin
      in human normal endocrine cells and related tumors of the digestive system.
AB  - Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able
      to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one
      alpha-subunit and one betaA-subunit (alpha-betaA), while activin A is a homodimer
      of the betaA-subunit (betaA-betaA). Their identification in several tissues has
      suggested that they have numerous physiological functions, acting as either
      paracrine or autocrine factors. The aim of this study was to evaluate the
      expression of activin A and inhibin A in normal endocrine cells and in 70
      endocrine tumours from different sites in the gastro-entero-pancreatic system,
      using specific monoclonal antibodies directed against the alpha- and betaA
      subunits of inhibin/activin. Immunoreactivity for the betaA-subunit, but not for
      the alpha-subunit, was observed in normal G, EC, and GIP cells of the antrum and
      duodenum, and in pancreatic A cells. BetaA-subunit expression was observed in G
      cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids.
      The alpha-subunit was found in rare cells in 7 of the 70 tumours and was
      colocalized with the betaA-subunit in only 1 tumor. Specific types of endocrine
      cells from the gut and pancreas appear to produce only activin A, a possible
      paracrine or autocrine modulator. Activin A is mainly produced by tumours derived
      from endocrine cells that normally express it.

PMID- 10071233
TI  - Irregular expression of hyaluronan and its CD44 receptor is associated with
      metastatic phenotype in laryngeal squamous cell carcinoma.
AB  - The distributions of hyaluronan (HA) and its CD44 receptor were studied in 24
      normal, 27 dysplastic samples of laryngeal epithelium and in 172 squamous cell
      carcinomas (LSCC), using a specific probe prepared from cartilage proteoglycan
      (bHABC, biotinylated hyaluronan binding complex) and a monoclonal antibody
      (Hermes 3). HA and CD44 were expressed similarly in all normal and about 90% of
      dysplastic and neoplastic laryngeal epithelia. In the normal epithelium HA and
      CD44 were homogeneously distributed throughout the epithelium, whereas the most
      superficial layers were negative. This was in contrast to the picture in
      dysplastic epithelium and well-differentiated invasive carcinomas, which were
      entirely HA and CD44 positive. Local areas with a low signal for HA and CD44 were
      present in 11% and 22% of the samples with dysplasia, and in 27% and 28% of those
      with carcinoma, respectively. The presence of this staining irregularity was
      associated with poor differentiation of the carcinoma, a significantly elevated
      mitotic index and a high frequency of nodal spreading and metastases.
      Furthermore, the irregular staining showed a trend towards poor disease-free
      survival, suggesting that an altered metabolism of HA is a common feature in LSCC
      and is associated with an aggressive growth pattern.

PMID- 10071234
TI  - Glycoprotein CD44 expression in colorectal neoplasms. An immuno-histochemical
      study including correlation with cathepsin D, extracellular matrix components,
      p53, Rb, bcl-2, c-erbB-2, EGFR and proliferation indices.
AB  - CD44 has diverse functions in cell-cell and cell-matrix interactions and may be a
      determinant of metastatic and invasive behaviour in carcinomas. The
      immunohistochemical expression of CD44 in a series of 110 colorectal carcinomas
      and 25 adenomas was examined using the monoclonal mouse anti-human phagocytic
      glycoprotein-1, CD44 (clone DF 1485) in correlation with the expression of
      basement membrane (BM) antigens (type IV collagen, laminin), fibronectin,
      cathepsin D, p53, Rb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA)
      and with other conventional clinicopathological variables. In adenomas, low CD44
      expression (<10% of neoplastic cells) was present in 16%, moderate (10-50% of
      neoplastic cells) in 52% and extensive (>50% of neoplastic cells) in 32% of
      cases. In carcinomas, low CD44 expression was found in 14.5%, moderate in 28.2%
      and extensive in 57.30%. Although the CD44 expression was higher in carcinomas
      than in adenomas, we found no statistically significant difference between these
      two groups. CD44 expression in carcinomas was positively correlated with tumour
      size (P=0.018), tumour cells cathepsin D (P=0.022), stromal cell cathepsin D
      (P=0.003) and Rb protein (P=0.021). An inverse correlation was observed between
      CD44 and the anti-apoptotic protein expression bcl-2 in adenocarcinomas (P=0.039)
      and in adenomas (P=0.021). These data suggest that CD44 may be involved in the
      process of invasion and metastasis, probably with the cooperation of cathepsin D.
      Its expression may be an indicator of poor prognosis in colorectal
      adenocarcinomas.

PMID- 10071235
TI  - Absence of Kaposi's sarcoma-associated virus (human herpesvirus-8) sequences in
      angiosarcoma.
AB  - Kaposi's sarcoma-associated virus (human herpesvirus-8 [HHV8]) sequences have
      been identified in both AIDS-associated and AIDS-non-associated Kaposi's sarcoma,
      but data relating to the detection of HHV8 sequences in angiosarcoma are
      variable. One study showed HHV8 sequences in 29% (7/24) of angiosarcomas, but
      others have not confirmed these results. We evaluated 33 angiosarcomas for HHV8
      sequences to determine the frequency of this virus in angiosarcomas and its
      possible pathogenetic significance. Five cases of Kaposi's sarcoma from HIV
      positive patients were used as positive controls. Five additional cases of
      Kaposi's sarcoma collected approximately 40-50 years ago were also analysed, and
      three were HHV8 positive. None of the angiosarcomas revealed HHV8 sequences after
      the standard 35 cycles of PCR. In 6 cases, nested PCR revealed the presence of
      HHV8 sequences. These results were not reproducible when outer primers (based on
      sequences outside of the earlier PCR products) were used for amplification. This
      suggests that the HHV8 sequences detected in 6 cases represent a low level of
      contamination. In contrast, HHV8 sequences were found in all Kaposi's sarcomas
      with well-preserved DNA after standard 35-cycle PCR amplification. These findings
      confirm a close association between Kaposi's sarcoma and HHV8 infection and
      suggest that HHV8 is not involved in the pathogenesis of angiosarcoma.

PMID- 10071236
TI  - 5'-Cytosine DNA-methyltransferase mRNA levels in hereditary colon carcinoma.
AB  - DNA methylation plays an important part in the regulation of gene expression.
      Alterations in DNA methylation in tumours have been reported and have been used
      to generate hypotheses about mutagenesis and silencing of tumour suppressor
      genes. However, the underlying mechanism is still poorly understood, and
      conflicting data on the levels of overexpression of 5'-cytosine DNA
      methyltransferase in sporadic colon carcinoma have been published. We used a
      competitive RT-PCR assay for quantification of mRNA of 5'-cytosine DNA
      methyltransferase in colon biopsies obtained from patients with hereditary colon
      carcinoma syndromes and compared the results with those obtained in a control
      group. No significant difference was found between the flat mucosa of FAP
      patients and the mucosa of the control group. In FAP and HNPCC patients, the 5'
      cytosine DNA methyltransferase mRNA levels of adenomas were significantly higher
      (P<0.05) than of flat mucosa in the same group, but both showed great variability
      from patient to patient. Our findings suggest that the mRNA levels of
      methyltransferase cannot be used as predictive marker for screening in families
      affected by hereditary colon carcinoma.

PMID- 10071237
TI  - Expression patterns of type II pneumocyte apical surface glycoconjugates in lung
      adenocarcinoma cells.
AB  - Monoclonal antibodies and lectins were used to examine the expression patterns of
      apical membrane oligosaccharide sequences specific to type II pneumocytes in
      atypical adenomatous hyperplasia (AAH) and lung cancer. Atypical cells of AAH and
      papillary adenocarcinoma cells expressed abundant sialyl Thomsen-Friedenreich
      (TF) antigen: this was not observed in acinar adenocarcinoma, bronchioloalveolar
      carcinoma with mucin production or squamous cell carcinoma. Sialyl Tn antigens
      was also detected on a few cells in AAH and papillary adenocarcinomas. Asialo TF
      and Tn antigen were not observed on the surface of carcinoma cells of any type.
      Alpha(alpha)2,3-linked sialic acids predominated in type II pneumocyte, AAH and
      papillary adenocarcinoma, whereas ciliated columnar cells expressed alpha2,6
      linked sialic acids. Lewisx and sialyl Lewisx antigens capped the TF antigen in
      both O- and N-linked side chains on the surface of AAH and papillary
      adenocarcinoma cells, but were not expressed by type II pneumocytes. The findings
      demonstrate that papillary adenocarcinoma cells resemble type II pneumocytes in
      that they express abundant sialyl TF surface antigen, but they also express TF
      related antigens not found in type II pneumocytes. Apical surface glycoconjugates
      of AAH have structural characteristics shared by both type II pneumocytes and
      papillary adenocarcinoma cells.

PMID- 10071238
TI  - Simultaneous detection of DNA fragmentation (apoptosis), cell proliferation (MIB
      1), and phenotype markers in routinely processed tissue sections.
AB  - In situ DNA fragmentation assays have proved to be particularly useful in the
      detection of apoptosis in routinely processed, paraffin-embedded tissue sections.
      In the present study, a triple-antigen labelling technique was performed to
      demonstrate DNA fragmentation (apoptosis), cell proliferation (MIB-1), and
      phenotypic markers in the same tissue section. The in situ apoptosis assay was
      conducted with the TUNEL method developed by a avidin-biotin alkaline phosphatase
      complex (ABcomplex/AP). The proliferation-associated MIB-1 antigen was
      demonstrated in the second staining sequence by the avidin-biotin peroxidase
      method (ABC). The phenotypic markers chromogranin A or prostate-specific antigen
      (PSA) were visualized by the alkaline phosphatase anti-alkaline phosphatase
      method (APAAP) in the third staining sequence. The feasibility of this triple
      labelling technique was tested in formalin-fixed, paraffin-embedded tissue of
      prostatic adenocarcinomas from 8 patients with recurrent, hormone-refractory
      disease. Although these tumours revealed marked neuroendocrine differentiation,
      cell proliferation and apoptosis were detected exclusively in non-endocrine
      (chromogranin A-negative) tumour cells that expressed PSA variably. The triple
      labelling protocol described here allows the phenotypic characterization of
      proliferating and apoptotic cell populations in the same tissue section. It may
      be useful in studies of tissue kinetics in physiological and pathological
      processes.

PMID- 10071239
TI  - Nutrient-dependent distribution of insulin and glucokinase immunoreactivities in
      rat pancreatic beta cells.
AB  - Functional heterogeneity among pancreatic beta cells is a characteristic feature
      of the islets of Langerhans. Under physiological conditions, beta cells in the
      pancreas of fed rats exhibited heterogeneous immunohistochemical staining for
      insulin and glucokinase. Intracellular beta cell glucokinase staining was either
      faint or dense. In the pericapillary space beta cell glucokinase immunoreactivity
      had a polar orientation, with the highest density in cytoplasmic regions close to
      the blood vessels. Starvation resulted in a loss of heterogeneity with
      homogeneous insulin staining in all beta cells of the islets, and this was
      accompanied by a loss of heterogeneous glucokinase staining. The intracellular
      polarity of glucokinase staining in contact to blood vessels also disappeared
      after starvation. Refeeding resulted in the reappearance of intercellular
      heterogeneity. In dependence on the functional demand, the endocrine pancreas
      recruited insulin from beta cells according to a well-defined hierarchy, with an
      initial preferential mobilization of medullary beta cells. In the course of this
      process intracellular polarity of glucokinase staining reappeared in areas of the
      beta cell with functional contact to the GLUT2 glucose transporter in the plasma
      membrane. This can be regarded as the morphological correlate of an activation of
      the glucose signal recognition apparatus. Interestingly, the study also provides
      evidence that the changes in glucokinase distribution apparently preceded those
      in insulin distribution, which is in keeping with the central role of glucokinase
      as the glucose sensor of the pancreatic beta cell.

PMID- 10071240
TI  - Histopathological and biochemical studies on pancreatic fibrosis in WBN/Kob rats.
AB  - We investigated the time-course of changes in pancreatic fibrosis accompanied
      with pancreatitis in WBN/Kob rats. The areas of fibrosis and fatty replacement
      were analysed morphometrically, and biochemical measurements of pancreatic and
      plasma prolyl hydroxylase and of pancreatic collagenase were assessed. Male rats
      showed acute pancreatitis at 2-3 months of age, lesions that later underwent a
      transition to widespread fibrosis. The fibrosis then decreased, and the fibrotic
      tissue was replaced with adipose tissue. Morphometrically, the fibrotic area
      reached its maximal size when the rats were 4 months old, diminishing thereafter.
      The fibrosis occurred mainly in the intralobular space, and was principally
      attributable to type-III collagen. Type-I collagen scarcely appeared throughout
      the experimental period. Alpha-Smooth muscle actin appeared in and around
      myofibroblasts that developed in an early stage and diminished later in
      accordance with the progressive manner of fibrosis. The plasma prolyl hydroxylase
      level was higher in males than in females from 4 through 10 months of age.
      Pancreatic collagenase activity in the males also increased during the same
      period. These findings suggest that pancreatic fibrosis in male WBN/Kob rats is
      affected by the balance between prolyl hydroxylase and collagenase.

PMID- 10071241
TI  - Eradication of Helicobacter pylori heals atrophic corpus gastritis caused by long
      term treatment with omeprazole.
AB  - Long-term treatment with proton pump inhibitors in patients with Helicobacter
      pylori gastritis can lead to atrophic changes in the corpus mucosa. What is still
      unclear, however, is whether this atrophy can regress in response to Helicobacter
      pylori eradication. We report on a male patient with Helicobacter pylori
      gastritis receiving long-term treatment (4 years) with omeprazole for
      gastrooesophageal reflux disease, who developed autoaggressive gastritis with
      progressive atrophy, hypochlorhydria, hypergastrinaemia and nodular ECL-cell
      hyperplasia. To determine whether these changes might be induced to regress,
      Helicobacter pylori eradication therapy was administered. Ten months after
      Helicobacter pylori eradication autoaggressive lymphocytic infiltrates were no
      longer detectable, and the glands in the corpus mucosa had normalised despite
      continued treatment with omeprazole - a finding that was confirmed at two further
      follow-up surveys performed at 6-month intervals. This case report shows that
      atrophy of the corpus mucosa developing under long-term treatment with a proton
      pump inhibitor can be cured by eradicating Helicobacter pylori.

PMID- 10071242
TI  - Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month
      history of gastrointestinal tuberculosis.
AB  - We report on a 58-year-old Caucasian woman who went to a general practitioner
      about recurrent abdominal pain, night sweats and weight loss of a few weeks'
      duration. Once gynaecological disease had been ruled out, the patient was
      admitted to hospital with severe abdominal pain and intestinal obstruction and a
      right-sided hemicolectomy was performed. Following the investigation of
      osteolytic lumbar vertebrae, 18 months after visiting the general practitioner
      the patient was finally found to be suffering from generalized AA-amyloidosis
      secondary to gastrointestinal tuberculosis. This had been misinterpreted as
      Crohn's disease. Re-examination of the specimens from the right-sided
      hemicolectomy demonstrated that scanty deposits of AA-amyloid were present 9
      months after the first presentation. AA-amyloid can thus be present in serious
      inflammatory disease even during the first 9 months after the initial clinical
      presentation.

PMID- 10071243
TI  - From the "apparato reticolare interno" to "the Golgi": 100 years of Golgi
      apparatus research.
AB  - The year 1998 is the centenary of the Golgi apparatus. It is an occasion to pay
      tribute to Camillo Golgi and the other pioneers of Golgi apparatus research. From
      the very beginning, the discussion of the Golgi apparatus was characterized by a
      great variety of theories and innovative terminology, with signs of keen interest
      already evident during the era of light microscopy.

PMID- 10071244
TI  - Human cytomegalovirus infection in foci of Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune
      regulation, and increasingly, evidence showing that the tissue damage in LCH
      involves lymphokines and pro-inflammatory cytokines is reported. We detected
      human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by
      immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the
      nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV
      was probably an early antigen. In situ hybridization revealed signals for HCMV
      DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was
      performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7
      positive cases were also positive for HCMV by ISH and IHC. These findings
      suggested that early phase infection or reactivation of HCMV occurred in the LCH
      lesions. HCMV infection may be accompanied by impaired cytokine production. Our
      study also suggested a relationship between HCMV infection and expression of
      TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant
      fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA
      were detected. These findings suggest that in some cases LCH is associated with
      HCMV infection.

PMID- 10071245
TI  - In serous ovarian neoplasms the frequency of Ki-ras mutations correlates with
      their malignant potential.
AB  - We analysed 44 tissue samples from serous ovarian neoplasms of different
      malignant potential for Ki-ras mutations by denaturing gradient gel
      electrophoresis (DGGE) and direct sequencing after microdissection. Point
      mutations at codon 12 were found in 7 of 20 tumours of low malignant potential
      (LMP) (35%) and in 2 of 6 well-differentiated carcinomas (33%). In contrast, no
      mutations were detected in the 11 poorly differentiated ovarian carcinoma samples
      or in the 7 serous cystadenomas. The frequency of Ki-ras mutations in serous
      ovarian tumours seems to correlate with the malignant potential of the neoplasms.
      The data favour the hypothesis of a de novo development of poorly differentiated
      ovarian carcinomas and do not support an evolution from LMP tumours or well
      differentiated carcinomas.

PMID- 10071246
TI  - Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma
      sequence.
AB  - Syndecan-1, a transmembrane heparan sulphate proteoglycan (HSPG), functions as a
      matrix receptor on the basal surface of epithelial cells. It also co-localizes
      with E-cadherin at the lateral cell surface where its function is uncertain.
      Tumour development in the large bowel is associated with loss of normal
      epithelial adhesion and altered patterns of expression of cell adhesion
      molecules, possibly including syndecan-1. To evaluate changes in syndecan-1
      expression during the development of colorectal neoplasia, 59 adenomas and 20
      carcinomas arising from adenomas were investigated by immunohistochemistry. The
      staining intensity and distribution of syndecan-1 and E-cadherin in sequential
      sections was examined, semi-quantified and compared. Staining of syndecan-1 and E
      cadherin was uniform in normal colorectal epithelial cells, and located at the
      basolateral surface. No significant change was seen in either molecule in mildly
      or moderately dysplastic adenomas. A significant reduction in expression of both
      syndecan-1 and E-cadherin was seen in severely dysplastic epithelium as compared
      to moderate dysplasia (P = 0.001 and P = 0.004 respectively). Similarly, there
      was a significant reduction of both molecules in carcinomas compared with
      associated adenomas (syndecan-1 P = 0.00003; E-cadherin P = 0.002). In both cases
      the loss of syndecan-1 expression was more striking than that of E-cadherin.
      Previous in vitro studies have shown that epithelial cells made deficient in
      syndecan-1 cease to express E-cadherin, suggesting a causal association. Our
      results support these findings and indicate that disruption of cell-matrix
      adhesion is critical in colorectal carcinogenesis, probably preceding changes in
      the purely homotypic cell-cell adhesion mediated by E-cadherin.

PMID- 10071247
TI  - Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic
      alcohol abusers.
AB  - Excessive consumption of alcoholic beverages may be associated with
      gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear
      whether or not chronic alcohol ingestion damages the mucosa of the small
      intestine. We investigated the effect of chronic alcohol abuse on the duodenal
      mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal
      biopsy specimens were obtained during upper gastrointestinal endoscopy from 50
      chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological
      studies were performed by routine histology, immunohistochemistry and electron
      microscopy. Morphometry of duodenal tissues was performed with a computerized
      image analyser. No significant duodenal epithelial changes were found in
      alcoholics, despite an evident reduction in the enterocyte turnover.
      Myofibroblast-like cells were significantly increased in the villus stroma of
      alcoholics in comparison to controls. These cells stained positively for desmin,
      alpha-smooth muscle actin and for several ECM components. In alcohol abusers the
      thickness of the mucosal basement membrane was greater and the staining for
      collagen I and III was enhanced both in the basement membrane and in the villus
      stroma. A higher expression of tenascin was also seen at the base of villi of
      alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is
      associated with a transformation of villus juxta-parenchymal cells into active
      subepithelial myofibroblast-like cells able to produce different ECM components.

PMID- 10071248
TI  - Reconstruction of pleomorphic adenoma of the salivary glands in three-dimensional
      collagen gel matrix culture.
AB  - The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro
      using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells
      were isolated from three parotid gland tumours and cultured as monolayers, after
      which they were subcultured in floating-collagen gel sandwiches. Cells cultured
      in both conditions were immunohistochemically characterized and compared using
      antibodies against various proteins representative of each histological component
      of salivary glands. Monolayers had myoepithelial characteristics, being positive
      for vimentin and alpha-smooth muscle actin. In collagen gels, however, the cells
      assembled in epithelial nests, showing an architecture similar to that of
      pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that
      were positive for epithelial markers, surrounded by myoepithelial cells. Collagen
      gel culture induces multidirectional differentiation of adenoma cells, suggesting
      that pleomorphic adenomas originate from stem or reserve cells.

PMID- 10071249
TI  - Variable expression of heparan sulfate epitopes in crescents of human
      glomerulonephritis.
AB  - Crescentic glomerulonephritis leads to a rapid loss of renal function. Although
      glomerular crescents are rich in extracellular matrix (ECM), the composition and
      genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major
      ECM molecule and has polymeric structure of great variability. Recent findings
      that alterations in HS epitopes are associated with renal pathology prompted us
      to hypothesize that specific HS epitopes might be expressed in the evolution of
      crescents. We reviewed clinical records of 724 patients who underwent renal
      biopsy and found 21 patients with rapidly progressive glomerulonephritis.
      Immunohistochemistry was performed using monoclonal antibodies (mAbs) against
      well-defined HS epitopes. One mAb was directed against unsaturated uronic acid
      residues generated during the selective removal of HS by heparitinase (a), and a
      further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions
      of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and
      crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular
      crescents but not to fibrous crescents, the periglomerular areas and
      noncrescentic intraglomerular areas. We concluded there are regional differences
      in HS epitope expression, although HS are ubiquitous components of glomerular
      ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in
      crescent formation.

PMID- 10071250
TI  - Determination of the prognostic significance of cyclin B1 overexpression in
      patients with esophageal squamous cell carcinoma.
AB  - Recent studies have identified a family of proteins referred to as cyclins, which
      control the cell cycle. Cyclin B1 activates cdc2, which regulates cell
      progression through the G2 and M phases. The main aim of this study was to
      examine the relationships between the cyclin B1 expression in human esophageal
      squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of
      the patients. Eighty-seven cases of primary human SCC consecutively obtained at
      esophagectomy were immunohistochemically studied using an anti-human cyclin B1
      protein antibody (2H1-H6). The relationship between cyclin B1 expression and
      clinicopathological factors, including prognosis, were also statistically
      assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was
      detected in 72.4% (63/87): heterogeneous pattern in 37.9% (33/87) and homogeneous
      pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was
      significantly higher in cases with invasion deeper than the muscularis propria
      (P<0.005) and with venous invasion (P<0.01) than in other cases. Patients whose
      SCCs expressed high levels of cyclin B1 protein had a significantly poorer
      prognosis than did the other patients (P<0.05). Multivariate analysis
      demonstrated that cyclin B1 status was an important factor affecting survival
      (P<0.05). These findings demonstrated that overexpression of cyclin B1 protein is
      associated with tumor behavior and prognosis for patients with human esophageal
      SCC.

PMID- 10071251
TI  - Ultrastructural changes in myocardial cells of rats fed a low protein diet.
AB  - Ultrastructural changes in the ventricular myocardial cells in rats fed a low
      protein diet were examined by electron microscopy. The most striking changes were
      observed in the I-band region of the sarcomeres, which occurred very occasionally
      in myofibrils. In the sarcomere affected the I-band region was often fractured
      and/or disintegrated on one side, leaving an extended space, while the opposing I
      band region disappeared along with dislocation of the intact A-band toward the
      adjacent Z-line. This dislocation was presumably attributed to the elasticity of
      titins connecting between the end of thick filaments and the Z-line. Fractured I
      band regions were often accompanied by the dilated sarcoplasmic reticulum in the
      close vicinity of them. In some myofibrils the streaming and/or disruption of the
      Z-line were occasionally observed where disarrangement of thick and thin
      myofilaments were usually present. The study suggests that the fracture of the I
      band region, consisting of actin and titin filaments, and the streaming of the Z
      line of myofibrils are due to a proteolytic action of calpain and/or cathepsin L,
      which are activated by leaked Ca2+ ion and/or by modification of internal
      circumstances of the cytoplasm induced by a low protein diet, thus resulting in a
      low cardiac output.

PMID- 10071252
TI  - Intramuscular mixed tumour with clonal chromosomal changes.
AB  - A case of an entirely intramuscular mixed tumour occurred in an 82-year-old man,
      who presented with a large mass in the region of the right triceps muscle. A
      lobulated tumour was seen, with plump, round epithelioid cells embedded in a
      chondromyxoid stroma. Immunohistochemical examination showed strong S100 protein
      and pancytokeratin positivity in most of the tumour cells. Cytogenetic analysis
      revealed complex clonal chromosomal changes: 47, XY, +i(2) (q10), -15, der(17)
      t(15; 17) (q11; p12), +r. Differential diagnosis against extraskeletal myxoid
      chondrosarcoma (EMC) may be problematic, particularly in an incisional biopsy.
      Chromosomal analysis can be very helpful in solving this problem, since EMC shows
      a specific reciprocal chromosome translocation characterised as t (9;22) (q22-31)
      (q11-12).

PMID- 10071253
TI  - Tall cell variant of papillary thyroid carcinoma with foci of columnar cell
      component.
AB  - We report a case of the tall call variant of papillary thyroid carcinoma with
      foci of columnar cell component in a 67-year-old Japanese man. Tall cell variant
      occupied more than 70% of the tumour, and columnar cell component was of two
      types in representative sections. One showed striking stratification of nuclei
      with scanty cytoplasm, and the other appeared clear. Characteristic nuclear
      features of papillary carcinoma were also observed in the area of the tall cell
      variant. The patient died of the thyroid cancer with aspiration pneumonia 10
      years and 6 months after operation. Although autopsy was not performed,
      metastatic lymph nodes of the neck removed during life also showed papillary
      carcinoma with both tall cell and columnar cell components. Our case indicates
      that tall cell and columnar cell variants may coexist in the same tumour although
      the pathogenesis remains unclear.

PMID- 10071254
TI  - Clonal chromosomal changes in juxta-articular myxoma.
AB  - Cytogenetic analysis of a juxta-articular myxoma revealed two distinct
      cytogenetically abnormal cell populations: inv(2)(p15q36) and +7, t(8;22)(q11-12;
      q12-13). These clonal chromosomal changes, the first to be reported in this
      tumour type, suggest that at least some juxta-articular myxomas are neoplastic
      rather than reactive in nature.

PMID- 10071255
TI  - Ossifying lipoma.
AB  - Lipomas are very common, but osseous changes within these tumours are rare. A
      lipoma with osseous components is presented, with an overview of the literature
      and pathogenesis of this unusual lesion and considerations relating to the
      differential diagnosis.

PMID- 10071256
TI  - Long-term morbidity and mortality trials with amlodipine.
AB  - Prospective controlled clinical trials with cardiovascular events and mortality
      as end points are needed to provide clinicians with a fully informed choice of
      optimal hypertensive therapy. Seven trials (six of them still ongoing) have
      provided insight into the effects of the third-generation calcium antagonist,
      amlodipine, on mortality and end-organ damage in patients with hypertension or
      other forms of cardiovascular disease. The completed PRAISE study has addressed
      the safety of amlodipine in patients with advanced heart failure (CHF). The trial
      showed that amlodipine does not increase mortality or morbidity in CHF patients
      and significantly reduces the risk for these end points in patients whose CHF has
      a nonischemic etiology. The PRAISE-2 study is now under way to further evaluate
      the benefits of amlodipine in nonischemic CHF patients. The ALLHAT trial compares
      the effects of standard diuretic treatment with three alternative treatments
      (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery
      disease (CAD) and nonfatal myocardial infarction (MI) in 40,000 hypertensive
      patients. The ASCOT trial compares the effects of amlodipine +/- perindopril with
      atenolol +/- bendrofluazide on fatal CAD and nonfatal MI in 18,000 high-risk
      patients. The PREVENT trial tests a similar hypothesis, looking at the effects of
      amlodipine on arterial atherosclerotic lesions, and the AASK trial is evaluating
      the effects of amlodipine on renal disease. The PRAISE trial has provided
      valuable information on the safety and efficacy of amlodipine in preventing death
      and disability in patients with CHF. The six ongoing trials will provide
      important additional information on the effect of amlodipine in patients with
      heart disease of other etiologies.

PMID- 10071257
TI  - Review of preclinical data of calcium channel blockers and atherosclerosis.
AB  - A variety of animal models have been used to determine whether calcium channel
      blockers exert an inhibitory effect on atherosclerotic lesion formation. These
      models include the cholesterol-fed rabbit, in which the lesions resemble the
      fatty-streak stage of atherosclerotic lesion development in humans. Diet-induced
      atherosclerosis in monkeys is also used and, in this case, the lesions resemble
      those found in humans, both in pathology and distribution. Other models involve
      mechanical injury superimposed on cholesterol feeding. Cellular and subcellular
      preparations are being used to investigate the mechanisms involved in the
      antiatherosclerotic activity of the calcium channel blockers. The ability of
      calcium channel blockers to slow atherosclerotic lesion formation is a class
      effect that is independent of their blood pressure-lowering effect, and occurs
      without any significant change in the plasma lipid profile. It is accompanied by
      a reduction in vessel wall cholesterol and calcium and is maintained over
      prolonged periods of treatment. The mechanisms that may be involved include
      inhibition of smooth muscle cell proliferation and migration, slowed platelet
      aggregation, restructuring of cholesterol-enriched cell membranes, enhanced gene
      expression for low-density lipoprotein receptor protein, inhibition of growth
      factor release, slowed calcium uptake, and restoration of endothelium-dependent
      relaxation.

PMID- 10071258
TI  - Pharmacologic effects of calcium channel blockers on restenosis.
AB  - The understanding and control of the healing process after percutaneous
      transluminal coronary angioplasty (PTCA) and of the pathogenesis of restenosis
      are incomplete. To date, only stent implantation has been shown to successfully
      reduce the rate of restenosis. Calcium channel blockers have positive effects on
      a number of processes that may be associated with restenosis, including reduction
      of platelet aggregation, minimization of vasospasm, and inhibition of mitogens.
      Clinical trials have therefore been performed to assess the effect of calcium
      channel blockers on restenosis and ischemia. A meta-analysis of five restenosis
      trials investigating calcium channel blockers demonstrated a 30% reduction in the
      risk for restenosis. The Coronary Angioplasty Amlodipine Restenosis Study
      (CAPARES) is therefore assessing the effect of amlodipine, a long-acting, third
      generation calcium channel blocker in angioplasty patients. Therapy (amlodipine 5
      mg with a forced titration to 10 mg once daily, or placebo), is begun 2 weeks
      before angioplasty and is continued for 4 months after the procedure. The
      rationale of CAPARES is that amlodipine may offer anti-ischemic protection
      before, during, and after angioplasty, may have more beneficial effects on
      restenosis and various clinical end points than calcium channel blockers used in
      previous trials, and may improve the long-term outcome of PTCA therapy.

PMID- 10071259
TI  - Atheroprotection with amlodipine: cells to lesions and the PREVENT trial.
      Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial.
AB  - Oxidized lipid and calcium regulatory abnormalities appear to play important
      roles in early atherogenesis secondary to cholesterol enrichment of the cell
      membrane in endothelial and arterial smooth muscle cells (SMCs). However, the
      link between the two is poorly understood. The findings reviewed here demonstrate
      that amlodipine has membrane-modifying and antioxidant actions at the cell
      membrane level in addition to its classical calcium channel blocking properties.
      These multiple pharmacologic actions may explain the cellular mechanisms of the
      atheroprotective effects of amlodipine in spontaneous atherogenesis and in
      accelerated atherosclerotic syndromes. Recent animal model studies have
      demonstrated that amlodipine inhibits the progression of atherosclerotic lesions
      and protects against restenosis after angioplasty. Amlodipine inhibits the
      cholesterol-induced increase in calcium permeability in SMCs, and has been shown
      to repair abnormalities in SMC membrane structure. Recent data have also
      demonstrated that amlodipine has a marked antioxidant action in membrane bilayers
      enriched with polyunsaturated fatty acids. However, these findings have been in
      animal models only; the efficacy of amlodipine in atheroprotection in humans
      cannot be predicted. The PREVENT trial has therefore been launched to examine the
      atheroprotective potential of amlodipine in spontaneous lesion development in
      humans with ischemic heart disease and in the prevention of restenosis after
      angioplasty.

PMID- 10071260
TI  - Back to the future: multiagent chemotherapy in ovarian cancer revisited.

PMID- 10071261
TI  - Lymphocyte-predominant Hodgkin's disease: how little therapy is enough?

PMID- 10071262
TI  - Phase I and pharmacologic study of the combination of paclitaxel, cisplatin, and
      topotecan administered intravenously every 21 days as first-line therapy in
      patients with advanced ovarian cancer.
AB  - PURPOSE: To evaluate the feasibility of administering topotecan in combination
      with paclitaxel and cisplatin without and with granulocyte colony-stimulating
      factor (G-CSF) support as first-line chemotherapy in women with incompletely
      resected stage III and stage IV ovarian carcinoma. PATIENTS AND METHODS: Starting
      doses were paclitaxel 110 mg/m2 administered over 24 hours (day 1), followed by
      cisplatin 50 mg/m2 over 3 hours (day 2) and topotecan 0.3 mg/m2/d over 30 minutes
      for 5 consecutive days (days 2 to 6). Treatment was repeated every 3 weeks. After
      encountering dose-limiting toxicities (DLTs) without G-CSF support, the maximum
      tolerated dose was defined as 5 microg/kg of G-CSF subcutaneously starting on day
      6. RESULTS: Twenty-one patients received a total of 116 courses at four different
      dose levels. The DLT was neutropenia. At the first dose level, all six patients
      experienced grade 4 myelosuppression. G-CSF support permitted further dose
      escalation of cisplatin and topotecan. Nonhematologic toxicities, primarily
      fatigue, nausea/vomiting, and neurosensory neuropathy, were observed but were
      generally mild. Of 15 patients assessable for response, nine had a complete
      response, four achieved a partial response, and two had stable disease.
      CONCLUSION: Neutropenia was the DLT of this combination of paclitaxel, cisplatin,
      and topotecan. The recommended phase II dose is paclitaxel 110 mg/m2 (day 1),
      followed by cisplatin 75 mg/m2 (day 2) and topotecan 0.3 mg/m2/d (days 2 to 6)
      with G-CSF support repeated every 3 weeks.

PMID- 10071263
TI  - Phase II study of cisplatin and vinorelbine as first-line chemotherapy in
      patients with carcinoma of the uterine cervix.
AB  - PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin
      (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with
      carcinoma of the uterine cervix that has not been previously treated with
      chemotherapy. PATIENTS AND METHODS: Fifty patients with cervical cancer were
      enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage
      optimal Simon design was applied. Thirteen responders of 29 treated patients were
      required to proceed beyond the first stage, and 28 responders were needed
      overall. RESULTS: Hematologic toxicity was mild, with neutropenia being the most
      frequent side effect. Nonhematologic toxicity was frequent but never severe; one
      patient had grade 3 peripheral neurotoxicity. Objective responses were recorded
      for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21
      patients (42%) achieved a partial response (PR). The response rate was 81.5% in
      patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB
      recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients
      (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent
      disease (three CRs + four PRs, for an overall rate of 46.7%). CONCLUSION: The
      combination of cisplatin and vinorelbine is an active regimen in the treatment of
      patients with early-stage and advanced carcinoma of the uterine cervix. The
      hematologic and nonhematologic toxicity of this combination is mild.

PMID- 10071264
TI  - Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma
      of the uterine cervix.
AB  - PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with
      metastatic or recurrent cancer of the cervix, and the combination of these two
      agents has shown activity and possible synergism in a variety of solid tumors. We
      administered this combination to patients with metastatic or recurrent cervical
      cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive
      patients were treated on an outpatient basis with paclitaxel 175 mg/m2
      administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2
      administered intravenously with granulocyte colony-stimulating factor support.
      The chemotherapy was administered every 3 weeks for a maximum of six courses.
      RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an
      objective response, including five complete responses and 11 partial responses.
      Responses occurred in 28% of patients with disease within the radiation field
      only and in 57% of patients with disease involving other sites. The median
      duration of response was 5.5 months, and the median times to progression and
      survival for all patients were 5 and 9 months, respectively. Grade 3 or 4
      toxicities included anemia in 18% of patients and granulocytopenia in 15% of
      patients. Fifty-three percent of patients developed some degree of neurotoxicity;
      21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel
      with cisplatin seems relatively well tolerated and moderately active in patients
      with metastatic or recurrent cervical cancer. The significant incidence of
      neurotoxicity is of concern, and alternative methods of administration of the two
      agents could be evaluated. Then, further study of this combination, alone or with
      the addition of other active agents, is warranted.

PMID- 10071265
TI  - Natural history of stage IV epithelial ovarian cancer.
AB  - PURPOSE: In this report we present the natural history, prognostic factors, and
      therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS
      AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the
      International Federation of Gynecology and Obstetrics. RESULTS: The site of stage
      IV-defining disease was cytologically positive pleural effusion in 63 patients,
      liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other
      sites in 15 patients, and disease at multiple stage IV-defining metastatic sites
      in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25
      patients (14.8%) were left with only microscopic residual disease or less than 2
      cm of macroscopic residual disease. The overall response rate to chemotherapy was
      56%; the complete response rate was 18%. The median progression-free survival was
      7.1 months, and the median overall survival was 13.4 months. The median overall
      survival of patients with positive pleural effusions only was 13.4 months as
      compared with 10.5 months for patients with visceral disease only, but this
      difference was not statistically significant. The 5-year survival rate was 7.6%,
      with only six patients surviving more than 5 years. Univariate and multivariate
      analysis showed that two parameters were associated with a shorter survival time:
      visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION:
      Patients with stage IV EOC initially respond to chemotherapy as often as those
      with less advanced disease, but the long-term prognosis is very poor. The size of
      residual disease is not a prognostic factor in this group of patients, and,
      therefore, the role of debulking surgery in these patients needs to be
      reconsidered.

PMID- 10071266
TI  - Clinical presentation, course, and prognostic factors in lymphocyte-predominant
      Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from
      the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's
      Disease.
AB  - PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's
      disease (LPHD) is both clinically and pathologically distinct from other forms of
      Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large
      scale clinical studies were lacking. This multicenter, retrospective study
      investigated the clinical characteristics and course of LPHD patients and
      lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according
      to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical
      data and biopsy material of all available cases initially submitted as LPHD were
      collected from 17 European and American centers, stained, and reclassified by
      expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD
      (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion
      (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were
      predominantly male, with early-stage disease and few risk factors. Patients with
      LRCHD were significantly older. Survival and failure-free survival rates with
      adequate therapy were similar for patients with LPHD and LRCHD, and were stage
      dependent and not significantly better than stage-comparable results for CHD
      (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple
      relapses, which is significantly more than the 5% of relapsing LRCHD patients who
      had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had
      significantly superior survival after relapse compared with LRCHD or CHD
      patients; however, this was partly due to the younger average age of LPHD
      patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical
      resemblance that was distinct from CHD; the course was similar to that of
      comparable nodular sclerosis and mixed cellularity patients. Thorough staging is
      necessary to detect advanced disease in LPHD and LRCHD patients. The question of
      how to treat such patients, either by reducing treatment intensity or following a
      "watch and wait" approach, remains unanswered.

PMID- 10071267
TI  - Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43
      patients from the Nebraska Lymphoma Study Group.
AB  - PURPOSE: To investigate whether primary mediastinal large B-cell lymphoma (PMLBL)
      is a distinct clinicopathologic entity with a more aggressive course than other
      diffuse large B-cell lymphomas (DLBL). MATERIALS AND METHODS: All patients with
      CD20-positive DLBL who presented with a mediastinal mass measuring at least 5.0
      cm and were treated with curative intent were identified. A control group of 352
      patients with nonmediastinal DLBL was selected for comparison. RESULTS: The 43
      patients with PMLBL had a male to female ratio of 20:23 and a median age of 42
      years. Stage I/II disease was present in 58% of the patients, with only 9% having
      bone marrow involvement. A complete remission was achieved in 63% of the
      patients, and the 5-year overall and failure-free survivals were 46% and 38%,
      respectively. Among the clinical variables, an elevated serum lactate
      dehydrogenase level, a low performance score, more than one extranodal site, and
      an intermediate or high International Prognostic Index score were predictive of
      poor survival. When compared with the DLBL group, a younger median age was the
      only clinical feature that was significantly different in the PMLBL group.
      CONCLUSION: The clinical features of PMLBL do not appear to be significantly
      different from those of nonmediastinal DLBL. Although the younger age of onset,
      slight female predominance, mediastinal location, and size of the mass may
      justify the recognition of PMLBL as a clinical syndrome, additional evidence is
      needed to define it as a distinct disease entity.

PMID- 10071268
TI  - Rituximab therapy in hematologic malignancy patients with circulating blood tumor
      cells: association with increased infusion-related side effects and rapid blood
      tumor clearance.
AB  - PURPOSE: Rituximab was recently approved for use in relapsed, low-grade non
      Hodgkin's lymphoma; however, few data exist regarding the safety of this agent in
      patients with a high number of tumor cells in the blood. METHODS AND RESULTS:
      After the observation at our institution of a rapid reduction of peripheral-blood
      tumor cells with associated severe pulmonary infusion-related toxicity in two
      patients with refractory hematologic malignancies, data on three additional cases
      were collected from physician-submitted reports of adverse events related to
      rituximab treatment. Five patients with hematologic malignancies possessing a
      high number of blood tumor cells were treated with rituximab and developed rapid
      tumor clearance. The median age was 68 years (range, 26 to 78 years). Patients
      were diagnosed with B-cell prolymphocytic leukemia (n = 2), chronic lymphocytic
      leukemia (n = 2), or transformed non-Hodgkin's lymphoma (n = 1). All of these
      patients had bulky adenopathy or organomegaly. All five patients developed a
      unique syndrome of severe infusion-related reactions, thrombocytopenia, rapid
      decrement in circulating tumor cell load, and mild electrolyte evidence of tumor
      lysis, and all required hospitalization. In addition, one patient developed
      ascites. These events resolved, and four patients were subsequently treated with
      rituximab without significant complications. CONCLUSION: Rituximab administration
      in patients who have a high number of tumor cells in the blood may have an
      increased likelihood of severe initial infusion-related reactions. These data
      also suggest that rituximab may have activity in a variety of other lymphoid
      neoplasms, such as chronic lymphocytic leukemia and B-cell prolymphocytic
      leukemia.

PMID- 10071269
TI  - Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell
      transplant recipients: use of high-resolution computed tomography.
AB  - PURPOSE: To obtain statistical data on the use of high-resolution computed
      tomography (HRCT) for early detection of pneumonia in febrile neutropenic
      patients with unknown focus of infection. MATERIALS AND METHODS: One hundred
      eighty-eight HRCT studies were performed prospectively in 112 neutropenic
      patients with fever of unknown origin persisting for more than 48 hours despite
      empiric antibiotic treatment. Fifty-four of these studies were performed in
      transplant recipients. All patients had normal chest roentgenograms. If pneumonia
      was detected by HRCT, guided bronchoalveolar lavage was recommended. Evidence of
      pneumonia on chest roentgenograms during follow-up and micro-organisms detected
      during follow-up were regarded as documentation of pneumonia. RESULTS: Of the 188
      HRCT studies, 112 (60%) showed pneumonia and 76 were normal. Documentation of
      pneumonia was possible in 61 cases by chest roentgenography or micro-organism
      detection (54%) (P < 10(-6)). Sensitivity of HRCT was 87% (88% in transplant
      recipients), specificity was 57% (67%), and the negative predictive value was 88%
      (97%). A time gain of 5 days was achieved by the additional use of HRCT compared
      to an exclusive use of chest roentgenography. CONCLUSION: The high frequency of
      inflammatory pulmonary disease after a suspicious HRCT scan (> 50%) proves that
      pneumonia is not excluded by a normal chest roentgenogram. Given the
      significantly longer duration of febrile episodes in transplant recipients, HRCT
      findings are particularly relevant in this subgroup. Patients with normal HRCT
      scans, particularly transplant recipients, have a low risk of pneumonia during
      follow-up. All neutropenic patients with fever of unknown origin and normal chest
      roentgenograms should undergo HRCT.

PMID- 10071270
TI  - Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant
      recipients: graft-versus-host disease and transplant-related mortality.
AB  - PURPOSE: To determine the risks of graft-versus-host disease (GVHD) and
      transplant-related mortality after allogeneic peripheral-blood stem-cell (PBSC)
      transplantation. PATIENTS AND METHODS: Between December 1994 and July 1996, 50
      consecutive patients with high-risk hematologic malignancies in first remission
      or relapse received high-dose therapy followed by transplantation of granulocyte
      colony-stimulating factor-mobilized, allogeneic PBSCs collected from HLA
      identical siblings. GVHD prophylaxis included cyclosporine and corticosteroids.
      RESULTS: As of April 1, 1998, 18 patients (36%+/-13%) survived with a median
      follow-up period of 767 days (range, 602 to 1,127 days). The actuarial
      probability of grades 2-4 acute GVHD was 0.37+/-0.14 (95% confidence interval).
      Of 36 assessable patients, 26 (72%+/-15%) developed chronic GVHD. The actuarial
      probability of chronic GVHD 2 years after transplantation was 0.87+/-0.15. Of 14
      progression-free survivors, 11 (79%+/-22%) have active, chronic GVHD. All 11
      patients require ongoing immunosuppression, and nearly two thirds have extensive
      disease. Thirteen patients died as a result of transplant-related mortality
      (26%+/-12%), six (12%) before and seven (14%) after day +100. CONCLUSION: We
      observed a high risk of chronic GVHD after allogeneic PBSC transplantation, which
      compromised the performance status of most long-term survivors and resulted in a
      relatively high risk of late transplant-related mortality. Approximately 75% of
      transplant-related deaths were associated with GVHD; thus, reduction in
      transplant-related mortality after allogeneic PBSC transplantation will require
      more effective strategies for the prophylaxis and/or treatment of GVHD.

PMID- 10071271
TI  - Age, sex, and smoking are predictors of circulating insulin-like growth factor 1
      and insulin-like growth factor-binding protein 3.
AB  - PURPOSE: Insulin-like growth factor (IGF-1) and its major binding protein (IGF
      BP3) have recently been implicated in the pathogenesis of several malignancies.
      However, anthropometric and lifestyle predictors of these hormones have not been
      elucidated. Here we report the results of a cross-sectional study. SUBJECTS AND
      METHODS: This cross-sectional study examines the relationship of a series of
      epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol
      consumption, and coffee drinking) with IGF-1 and IGF-BP3 in a sample of 130
      healthy adults. RESULTS: We observed that serum levels of IGF-1 are higher,
      whereas levels of IGF-BP3 are lower, in men than in women. In addition, serum
      levels of IGF-1 are independently and negatively associated with age and
      positively associated with pack-year history of smoking. Finally, serum levels of
      IGF-BP3 are independently and negatively associated with the number of cigarettes
      smoked per day or pack-year history of smoking. CONCLUSION: Age, sex, and smoking
      are independent predictors of IGF-1 and/or IGF-BP3. The influence of these
      epidemiologic variables on the pathogenesis of disease states associated with IGF
      1 and IGF-BP3 warrants further exploration.

PMID- 10071272
TI  - Sex differences in prognosis for children with acute lymphoblastic leukemia.
AB  - PURPOSE: Whether recent improvements in the treatment of childhood acute
      lymphoblastic leukemia (ALL) have nullified the adverse prognosis associated with
      male sex remains unclear. Therefore, we analyzed the survival experience and
      presenting clinical and laboratory features of boys and girls with newly
      diagnosed ALL who were treated at our institution over the past three decades.
      PATIENTS AND METHODS: One thousand one hundred fifty-one boys and 904 girls were
      treated in 13 consecutive Total Therapy studies between 1962 and 1994. An
      overview analysis was used to investigate the impact of sex on overall and event
      free survival, both for the entire cohort and for subgroups defined by treatment
      era and blast-cell immunophenotype. Stratified analyses were performed to adjust
      for treatment protocol and known risk factors, and in the modern treatment era,
      for protocol, immunophenotype, and the DNA content of leukemic cells (ie, DNA
      index). The pharmacokinetics of methotrexate, teniposide, and cytarabine, as well
      as the thiopurine methyltransferase activity of erythrocytes, were compared
      between boys and girls treated on a single protocol. RESULTS: Compared with
      girls, boys were more likely to have T-cell ALL (20.9% v 10.7%, P < .001) and
      seemed less likely to have a favorable DNA index (17.8% v 25.1%, P = .072). There
      were no other statistically significant differences between the two sexes with
      respect to presenting features, including leukemic-cell genetic abnormalities,
      nor were there significant sex differences in the pharmacokinetics of
      methotrexate, teniposide, or cytarabine or in erythrocyte thiopurine
      methyltransferase activity. Girls clearly fared better than boys (P < .001) on
      protocols used during the early era of treatment (10-year event-free survival +/-
      1 SE, 43.1%+/-2.1% v 31.5%+/-1.7%). Although prognosis improved for both sexes in
      the modern era, the difference in outcome between girls and boys persisted (P =
      .025) (10-year event-free survival, 73.4%+/-3.7% v 63.5%+/-4.0%). However,
      stratification of modern-era patients by protocol, immunophenotype, and DNA index
      mitigated statistical evidence of a sex difference in overall survival (P = .263)
      and event-free survival (P = .124). CONCLUSION: Although boys and girls alike
      have benefited from improvements in ALL therapy, these gains have not completely
      eliminated the sex difference in prognosis that has persisted since the early
      1960s. The apparent difference in outcome is partially explained by differences
      between boys and girls in the distributions of ALL immunophenotype and DNA index.

PMID- 10071273
TI  - Autologous hematopoietic stem-cell transplantation for relapsed or refractory
      Hodgkin's disease in children and adolescents.
AB  - PURPOSE: To determine the treatment outcome and clinical factors that are of
      prognostic significance for children and adolescents with relapsed or refractory
      Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and
      autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS:
      Fifty-three consecutive children and adolescents 21 years of age or younger with
      relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after
      transplantation, 29 patients (55%) were in a complete remission or maintained a
      continuous complete response, six (11%) had a partial response, and 11 (21%)
      failed to respond or had progressive disease. The failure-free survival (FFS) at
      5 years was 31%, and overall survival was 43%. Twenty-one patients died of
      progressive HD, and nine died secondary to transplantation-related complications,
      including two secondary leukemias. Prognostic factors important for FFS were
      normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%),
      compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and
      disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive
      disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There
      was no statistically significant difference in FFS or overall survival between
      age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with
      an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can
      result in long-term cures and should be considered for children and adolescents
      with relapsed HD.

PMID- 10071274
TI  - Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors
      for medulloblastoma in children: conclusions from the Children's Cancer Group 921
      randomized phase III study.
AB  - PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both
      before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was
      compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in
      children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS:
      Two hundred three eligible patients with an institutional diagnosis of MB were
      stratified by local invasion and metastatic stage (Chang T/M) and randomized to
      therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival
      and progression-free survival (PFS) +/- SE at 7 years were 55%+/-5% and 54%+/-5%,
      respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of
      63%+/-5% versus 45%+/-5%, respectively (P = .006). Upon central neuropathology
      review, 188 patients were confirmed as having MB and were the subjects for
      analyses of prognostic factors. Children aged 1.5 to younger than 3 years had
      inferior 5-year estimates of PFS, compared with children 3 years old or older (P
      = .0014; 32%+/-10% v 58%+/-4%, respectively). For MB patients 3 years of age or
      older, the prognostic effect of tumor spread (MO v M1 v M2+) on PFS was powerful
      (P = .0006); 5-year PFS rates were 70%+/-5%, 57%+/-10%, and 40%+/-8%,
      respectively. PFS distributions at 5 years for patients with M0 tumors with less
      than 1.5 cm2 of residual tumor, versus > or = 1.5 cm2 of residual tumor by scan,
      were significantly different (P = .023; 78%+/-6% v 54%+/-11%, respectively).
      CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1
      chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not
      extent of resection) is a predictor for PFS. Patients with M0 tumors, > or = 3
      years with < or = 1.5 cm2 residual tumor, had a 78%+/-6% 5-year PFS rate.
      Children younger than 3 years old who received a reduced XRT dosage had the
      lowest survival rate.

PMID- 10071275
TI  - Pamidronate reduces skeletal morbidity in women with advanced breast cancer and
      lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia
      Breast Cancer Study Group.
AB  - PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal
      morbidity in women with lytic bone metastases from breast cancer treated with
      hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with
      breast cancer who had at least one lytic bone lesion and who were receiving
      hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a
      2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24
      cycles. Patients were evaluated for skeletal complications: pathologic fractures,
      spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The
      skeletal morbidity rate (the ratio of the number of skeletal complications to the
      time on trial) was the primary efficacy variable. Bone pain, use of analgesics,
      quality of life, performance status, bone tumor response, and biochemical
      parameters were also evaluated. RESULTS: One hundred eighty-two patients who
      received pamidronate and 189 who received placebo were assessable. The skeletal
      morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients
      treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24
      cycles, the proportion of patients having had any skeletal complication was 56%
      in the pamidronate group and 67% in the placebo group (P = .027). The time to the
      first skeletal complication was longer for patients receiving pamidronate than
      for those given placebo (P = .049). There was no statistical difference in
      survival or in objective bone response rate. Pamidronate was well tolerated.
      CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion
      every 4 weeks in addition to hormonal therapy significantly reduces skeletal
      morbidity from osteolytic metastases.

PMID- 10071276
TI  - Management of breast cancer during pregnancy using a standardized protocol.
AB  - PURPOSE: No standardized therapeutic interventions have been reported for
      patients diagnosed with breast cancer during pregnancy. Of the potential
      interventions, none have been prospectively evaluated for treatment efficacy in
      the mother or safety for the fetus. We present our experience with the use of
      combination chemotherapy for breast cancer during pregnancy. PATIENTS AND
      METHODS: During the past 8 years, 24 pregnant patients with primary or recurrent
      cancer of the breast were managed by outpatient chemotherapy, surgery, or surgery
      plus radiation therapy, as clinically indicated. The chemotherapy included
      fluorouracil (1,000 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500
      mg/m2), administered every 3 to 4 weeks after the first trimester of pregnancy.
      Care was provided by medical oncologists, breast surgeons, and perinatal
      obstetricians. RESULTS: Modified radical mastectomy was performed in 18 of the 22
      patients, and two patients were treated with segmental mastectomy with postpartum
      radiation therapy. This group included patients in all trimesters of pregnancy.
      The patients received a median of four cycles of combination chemotherapy during
      pregnancy. No antepartum complications temporally attributable to systemic
      therapy were noted. The mean gestational age at delivery was 38 weeks. Apgar
      scores, birthweights, and immediate postpartum health were reported to be normal
      for all of the children. CONCLUSION: Breast cancer can be treated with
      chemotherapy during the second and third trimesters of pregnancy with minimal
      complications of labor and delivery.

PMID- 10071277
TI  - Dose-escalation study of docetaxel in combination with mitoxantrone as first-line
      treatment in patients with metastatic breast cancer.
AB  - PURPOSE: To define the maximum-tolerated dose (MTD) and the dose-limiting
      toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with
      metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one chemotherapy
      naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%)
      had performance status (World Health Organization [WHO]) 0, 29 (71%) were
      postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients
      received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone
      (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks. RESULTS: A total
      of 217 chemotherapy cycles were administered. Without recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the
      first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile
      neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea.
      With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20
      mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients
      developed neutropenia after the first cycle of treatment. A total of 19 episodes
      of febrile neutropenia (9% of the cycles) occurred during the whole period of the
      study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone
      (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte
      number was observed; immunophenotyping revealed that all lymphocyte
      subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six
      patients (15%) and one patient (2%), respectively. No cardiac toxicity was
      observed. Nine complete responses (22%) and 23 partial responses (56%) were
      achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%).
      The median duration of response was 12.5 months, and the median time to tumor
      progression was 14.5 months. CONCLUSION: The reported combination of docetaxel
      and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and
      effective regimen as first-line treatment in patients with MBC.

PMID- 10071278
TI  - Quantitative polymerase chain reaction for the detection of micrometastases in
      patients with breast cancer.
AB  - PURPOSE: Previous reports have indicated that reverse transcriptase polymerase
      chain reaction (RT-PCR) for cytokeratin 19 (CK-19) may be useful in the
      management of patients with breast cancer. However, the specificity of this
      technique is low, principally because of a high rate of false-positive results.
      To improve the specificity of this assay, we developed a quantitative RT-PCR
      methodology that enables an estimate to be made of the number of CK-19
      transcripts in blood and bone marrow samples. PATIENTS AND METHODS: We examined
      45 peripheral-blood samples and 30 bone marrow samples from patients with a
      variety of nonneoplastic conditions using nested RT-PCR for CK-19. We also
      examined bone marrow and peripheral-blood samples from 23 patients with primary
      breast cancer and peripheral-blood samples from 37 patients with metastatic
      breast cancer. The number of CK-19 transcripts was estimated in positive
      specimens by competitive PCR and normalized to the number of ABL transcripts as
      an internal control for the quality and quantity of cDNA. RT-PCR results were
      compared with the numbers of CK-19-positive cells detected by
      immunocytochemistry. RESULTS: Analysis of samples from patients without cancer
      enabled us to define an upper limit for the background ratio of CK-19 to ABL
      transcripts (1:1,000 for blood samples and 1:1,600 for bone marrow samples).
      Using these figures as cut-off points, elevated CK-19: ABL ratios were detected
      in peripheral-blood samples of 20 of 37 (54%) patients with metastatic breast
      cancer and in bone marrow samples of 14 of 23 (61%) patients with primary breast
      cancer. Only three of 23 (13%) primary breast cancer peripheral-blood samples and
      none of the control samples were positive by these criteria. Only two of 23
      patients (9%) with primary breast cancer showed immunocytochemically detectable
      cells in the blood; 10 of 23 (43%) showed immunocytochemically detectable cells
      in the bone marrow. Of 36 patients with metastatic breast cancer, eight (22%)
      showed positive events. CONCLUSION: Quantitative RT-PCR for CK-19 detects a
      percentage of patients with breast cancer and may enable the progression or
      regression of the disease to be monitored.

PMID- 10071279
TI  - Phase I trial of escalating doses of paclitaxel plus doxorubicin and dexrazoxane
      in patients with advanced breast cancer.
AB  - PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel given as a 3
      hour intravenous (IV) infusion that could be used in conjunction with doxorubicin
      and dexrazoxane, and to determine the effect of dexrazoxane on the
      pharmacokinetics of paclitaxel and doxorubicin. PATIENTS AND METHODS: Twenty-five
      patients with advanced breast cancer received dexrazoxane (600 mg/m2 by IV
      infusion over 15 minutes), followed 15 minutes later by doxorubicin (60 mg/m2
      IV), followed 15 minutes later by paclitaxel (150 or 175 mg/m2 by IV infusion
      over 3 hours) in cohorts of three to six patients using a standard phase I design
      without (group A) and with (group B) granulocyte colony-stimulating factor (G
      CSF). Treatment continued until there was a substantial decrease in the left
      ventricular ejection fraction (LVEF), congestive heart failure, progressive
      disease, or physician discretion to discontinue. RESULTS: The MTD of paclitaxel
      was 150 mg/m2, and adjunctive therapy with G-CSF was required to prevent febrile
      neutropenia. Dexrazoxane had no significant effect on the pharmacokinetics of
      paclitaxel or doxorubicin. After a median cumulative doxorubicin dose of 360
      mg/m2 (range, 60 to 870 mg/m2), no patient developed congestive heart failure or
      had a decrease in LVEF below normal. An objective response occurred in all five
      patients with locally advanced breast cancer and in eight of 20 patients (40%;
      95% confidence interval, 19% to 61%) with metastatic breast cancer. CONCLUSION:
      When combined with doxorubicin (60 mg/m2) and dexrazoxane (600 mg/m2), paclitaxel
      given as a 3-hour infusion had an MTD of 150 mg/m2, and G-CSF was required to
      prevent febrile neutropenia. Dexrazoxane had no effect on the pharmacokinetics of
      paclitaxel or doxorubicin. No patient in this trial had a decrease in the LVEF
      below normal, compared with about 20% to 50% of patients treated with doxorubicin
      and paclitaxel without dexrazoxane in other trials.

PMID- 10071280
TI  - Impact of consolidation radiotherapy in patients with advanced breast cancer
      treated with high-dose chemotherapy and autologous bone marrow rescue.
AB  - PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose
      chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced
      breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with
      metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and
      methotrexate (AFM) induction chemotherapy in a single-institution prospective
      trial. One hundred patients who achieved a complete response were randomized to
      receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone
      marrow rescue immediately after AFM, or to observation, with HDC to be
      administered at next relapse. Seventy-four of the 100 became eligible for RT; 53
      received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT
      was not randomized. The RT+ and RT- groups were similar with regard to number of
      involved sites, the fraction of patients with only local-regional disease, age,
      and interval since initial diagnosis. Local control at previously involved sites
      and distant sites was assessed with extensive radiologic and clinical evaluations
      at the time of first failure or most recent follow-up. The impact of RT on
      failure patterns, event-free survival, and overall survival was evaluated.
      RESULTS: Sites of first failure were located exclusively at previously involved
      sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free
      survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P =
      .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups,
      respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were
      treated with HDC without RT failed predominantly at the initial sites of disease.
      The addition of RT appeared to reduce the failure rate at initial disease sites
      and may improve event-free and overall survival. Our observations await
      verification in a trial in which assignment to RT is randomized.

PMID- 10071281
TI  - Additional value of whole-body positron emission tomography with fluorine-18-2
      fluoro-2-deoxy-D-glucose in recurrent colorectal cancer.
AB  - PURPOSE: To assess the additional value of the whole-body [18F]-2-fluoro-2-deoxy
      D-glucose positron emission tomography (FDG-PET) scan as a staging modality
      complementing conventional diagnostic methods (CDM) in patients suspected of
      having recurrent colorectal adenocarcinoma. PATIENTS AND METHODS: In 103
      patients, the discordances between FDG-PET and CDM results were identified and
      related to the final diagnosis obtained by histopathology or clinical follow-up
      (> 1 year). All FDG-PET studies were reviewed with full knowledge of the CDM
      findings. RESULTS: In a region-based analysis, discordances between CDM and FDG
      PET findings were found in 40 of 412 regions (10%). In these, FDG-PET had
      additional diagnostic value in 14 of 16 locoregional, six of seven hepatic, seven
      of eight abdominal, and eight of nine extra-abdominal regions. In a patient-based
      analysis, CDM categorized a subgroup of 60 patients as having resectable
      recurrent disease limited to the liver (n = 37) or locoregional region (n = 23).
      In 13 of these patients, there were discordant FDG-PET findings, detecting
      additional tumor sites in nine patients and excluding disease in three patients
      and yielding an additional diagnostic value in 20% of the patients. A second
      subgroup consisted of 13 patients with inconclusive CDM findings (n = 5) or with
      elevated plasma carcinoembryonic antigen levels and an otherwise negative
      conventional work-up (n = 8). In these patients, FDG-PET results were correct in
      eight of nine discordances, yielding a positive additional diagnostic value in
      62% of the patients. CONCLUSION: Whole-body FDG-PET can have a clear impact on
      the therapeutic management in the follow-up of patients with colorectal cancer.

PMID- 10071282
TI  - Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in
      patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer.
AB  - PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and
      oxaliplatin in patients with advanced colorectal cancer pretreated with
      leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients
      with metastatic colorectal cancer, who progressed while receiving or within 6
      months after discontinuing palliative chemotherapy with
      fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted
      of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15
      every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of
      scheduled chemotherapeutic drug administration, a 5-day course of granulocyte
      colony-stimulating factor (G-CSF) 5 microg/kg/d was given. RESULTS: The overall
      response rate was 42% for all 36 assessable patients (95% confidence interval,
      26% to 59%), including two complete remissions (6%). Thirteen additional patients
      (36%) had stable disease, and only eight (22%) progressed. The median time to
      treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median
      follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic
      toxicity was commonly observed, although according to the ANC-adapted use of G
      CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and
      4 granulocytopenia occurred in only five and two cases, respectively. The most
      frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which
      were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that
      the combination of irinotecan and oxaliplatin with or without G-CSF has
      substantial antitumor activity in patients with progressive
      fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was
      modest, with gastrointestinal symptoms constituting the dose-limiting side
      effects. Further evaluation of this regimen seems warranted.

PMID- 10071283
TI  - Phase I study of a weekly schedule of irinotecan, high-dose leucovorin, and
      infusional fluorouracil as first-line chemotherapy in patients with advanced
      colorectal cancer.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of a weekly schedule of
      irinotecan (CPT-11), leucovorin (LV), and a 24-hour infusion of fluorouracil (5
      FU24h) as first-line chemotherapy in advanced colorectal cancer and to assess
      preliminary data on the antitumor activity. PATIENTS AND METHODS: Twenty-six
      patients with measurable metastatic colorectal cancer were entered onto this
      phase I study. In the first six dose levels, fixed doses of CPT-11 (80 mg/m2) and
      LV (500 mg/m2) in combination with escalated doses of 5-FU24h ranging from 1.8 to
      2.6 g/m2 were administered on a weekly-times-four (dose levels 1 to 4) or weekly
      times-six (dose levels 5 to 6) schedule. The dose of CPT-11 was then increased to
      100 mg/m2 (dose level 7). RESULTS: Seventy-nine cycles of 5-FU24h/LV with CPT-11
      were administered in an outpatient setting. No dose-limiting toxicities were
      observed during the first cycle at dose levels 1 to 6, but diarrhea of grade 4
      (National Cancer Institute common toxicity criteria) was observed in three
      patients after multiple treatment cycles. Other nonhematologic and hematologic
      side effects, specifically alopecia and neutropenia, did not exceed grade 2. With
      the escalation of CPT-11 to 100 mg/m2 (dose level 7), diarrhea of grade 3 or
      higher was observed in four of six patients during the first cycle; thus, the MTD
      was achieved. Sixteen of 25 response-assessable patients (64%; 95% confidence
      interval, 45% to 83%) achieved an objective response. CONCLUSION: The recommended
      doses for further studies are CPT-11 80 mg/m2, LV 500 mg/m2, and 5-FU24h 2.6 g/m2
      given on a weekly-times-six schedule followed by a 1-week rest period. The
      addition of CPT-11 to 5-FU24h/LV seems to improve the therapeutic efficacy in
      terms of tumor response with manageable toxicity.

PMID- 10071284
TI  - Front-line treatment of advanced non-small-cell lung cancer with docetaxel and
      gemcitabine: a multicenter phase II trial.
AB  - PURPOSE: To evaluate the tolerance and efficacy of the combination of docetaxel
      and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Fifty-one chemotherapy-naive patients with NSCLC were
      treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel
      100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150
      microg/m2, subcutaneously) support from day 9 to day 15. Treatment was repeated
      every 3 weeks. RESULTS: The patients' median age was 64 years. The World Health
      Organization performance status was 0 to 1 in 39 patients and 2 in 12 patients.
      Fifteen patients (29%) had stage IIIB disease, and 36 (71%) had stage IV;
      histology was mainly squamous cell carcinoma (59%). A partial response was
      achieved in 19 patients (37.5%; 95% confidence interval, 24% to 50%); stable
      disease and progressive disease were each observed in 16 patients (31.4%). The
      median duration of response and the time to tumor progression were 5 and 6
      months, respectively. The median survival was 13 months, and the actuarial 1-year
      survival was 50.7%. Grade 4 anemia and thrombocytopenia were rare (2%). Four
      patients (8%) developed grade 3 or 4 neutropenia, and all were complicated with
      fever; there was no treatment-related death. Grade 3 or 4 diarrhea occurred in
      three patients (6%), grade 2 or 3 neurotoxicity in four patients (8%), grade 2 or
      3 asthenia in 10 patients (20%), and grade 2 or 3 edema in 10 patients (20%).
      CONCLUSION: The combination of docetaxel/gemcitabine is well tolerated, can be
      used for outpatients, and is active for the treatment of advanced NSCLC. This
      treatment merits further comparison with other cisplatin- or carboplatin-based
      combinations.

PMID- 10071285
TI  - Phase I-II study of gemcitabine and carboplatin in stage IIIB-IV non-small-cell
      lung cancer.
AB  - PURPOSE: Platinum-based chemotherapy currently represents standard treatment for
      advanced non-small-cell lung cancer. Gemcitabine is one of the most interesting
      agents currently in use in advanced non-small-cell lung cancer, and high response
      rates have been reported when it is administered in combination with cisplatin.
      The aim of the present study was to evaluate the combination of gemcitabine and
      carboplatin in a phase I-II study. PATIENTS AND METHODS: Chemotherapy-naive
      patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at
      area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an
      initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step.
      Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28
      day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which
      was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic
      toxicity. RESULTS: Neutropenia was DLT, inasmuch as it occurred in three of five
      patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild.
      Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II
      studies. An objective response was observed in 13 (50%) of 26 patients, including
      four complete responses (15%) and nine partial responses (35%). Median duration
      of response was 13 months (range, 3 to 23 months). Median overall survival was 16
      months (range, 3 to 26 months). CONCLUSION: The combination of gemcitabine and
      carboplatin is well tolerated and active. Neutropenia was DLT. The observed
      activity matches that observable in cisplatin-gemcitabine studies, whereas
      duration of response and survival are even higher. A phase II trial is under way.

PMID- 10071286
TI  - Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients
      resistant to cyclophosphamide, doxorubicin, and etoposide: a non-cross-resistant
      schedule.
AB  - PURPOSE: To evaluate the efficacy of paclitaxel and carboplatin (PC) in small
      cell lung cancer (SCLC) patients resistant to cyclophosphamide, doxorubicin, and
      etoposide (CDE). PATIENTS AND METHODS: We performed a phase II study with PC in
      SCLC patients who relapsed within 3 months after first-line treatment with CDE.
      Paclitaxel administration (175 mg/m2 by a 3-hour intravenous infusion) was
      followed by a 30-minute infusion of carboplatin (area under the curve 7; Chatelut
      formula) once every 3 weeks for five cycles. Dexamethasone, clemastine, and
      ranitidine were standard premedication before every cycle. RESULTS: Included were
      35 patients (median age, 59 years; 16 with limited disease and 19 with extensive
      disease; Eastern Cooperative Oncology Group performance status of < or = 1;
      median time off treatment 6 weeks) who were previously treated with CDE (n = 33),
      oral etoposide (n = 2), and reinduction CDE (n = 15); only one patient had
      received three CDE treatments of five cycles. The CDE regimen was followed by
      local thoracic radiotherapy in seven patients. Hematologic toxicity of grade 3 or
      4, for leukopenia was 27% and 6%, for thrombocytopenia 21% and 13%, and for
      anemia 17% and 0%, respectively, for a total of 132 cycles. Two patients had
      neutropenic fever; no toxic death occurred. Nonhematologic toxicity was
      paresthesia CTC grade 3, diarrhea grade 4, and myalgia grade 3 in one patient
      each. Reversible paresthesia (CTC grade 1 and 2) in toes and fingers was reported
      in 69% of patients. Thirty-four patients were assessable for response: complete
      response in two patients, partial response in 23 patients, stable disease in
      eight patients, and progressive disease in one patient (response rate, 73.5%; 95%
      confidence interval, 59% to 88%). One patient was found to have atypical
      carcinoid at pathologic review and was excluded. Median time to progression was
      21 weeks (range, 3 to 40 weeks). Median survival was 31 weeks (range, 6 to 112
      weeks). One-year survival was 9%. CONCLUSION: Second-line PC in CDE-resistant
      SCLC patients yields a high response rate and seems non-cross-resistant to CDE.
      Toxicity was mild in these poor-prognosis patients.

PMID- 10071287
TI  - Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS
      germ cell tumors.
AB  - PURPOSE: A prospective phase II study was initiated to assess the response rate,
      survival, and late effects of treatment in patients with newly diagnosed CNS germ
      cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy
      prescribed by extent of disease, histology, and response to chemotherapy.
      PATIENTS AND METHODS: Seventeen patients aged 8 to 24 years with histologically
      proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily
      for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine
      patients had germinomas; eight had mixed GCT. Four patients (three with
      germinomas and one with mixed GCT) presented with leptomeningeal dissemination.
      RESULTS: Radiographically, 14 of 17 patients were assessable for response; 11
      patients experienced complete regression, and three had major partial regression
      before radiation. Six of seven assessable patients with elevated CSF levels of
      alpha-fetoprotein or betahuman chorionic gonadotropin had normalization with
      chemotherapy alone; all normalized with combined chemotherapy and radiation
      therapy. All 17 patients are alive without evidence of disease (median follow-up,
      51 months). One patient developed a relapse in the spinal leptomeninges and was
      rendered free of disease with spinal radiation more than 5 years ago. One patient
      developed carotid stenosis requiring surgery. Thus far, only minimal long-term
      deterioration in neurocognitive function has been detected as a consequence of
      protocol treatment. CONCLUSION: Conventional-dose intravenous chemotherapy with
      etoposide and cisplatin can effect tumor regression in a high proportion of
      patients with CNS GCT, including those with leptomeningeal metastases. Acute and
      long-term toxicities are acceptable. Progression-free survival and overall
      survival are excellent.

PMID- 10071288
TI  - Semen quality and reproductive hormones before orchiectomy in men with testicular
      cancer.
AB  - PURPOSE: To obtain information about preorchiectomy gonadal function in patients
      with testicular germ cell cancer to improve the clinical management of fertility
      and other andrologic aspects in these men. PATIENTS AND METHODS: In group 1, a
      group of 83 consecutive patients with testicular germ cell cancer (TGCC)
      investigated before orchiectomy, semen analysis was carried out in 63 patients
      and hormonal investigations, including measurement of follicle-stimulating
      hormone, luteinizing hormone (LH), testosterone, estradiol, sex hormone-binding
      globulin (SHBG), inhibin B, and human chorionic gonadotropin (hCG), in 71
      patients. Hormone levels in patients with elevated hCG (n = 41) were analyzed
      separately. To discriminate between general cancer effects and specific effects
      associated with TGCC, the same analyses were carried out in a group of 45
      consecutive male patients with malignant lymphoma (group 2). Group 3 comprised
      141 men employed in a Danish company who served as controls in the comparison of
      semen parameters. As a control group in hormone investigations, 193 men were
      selected randomly from the Danish National Personal Register to make up group 4.
      RESULTS: We found significantly lower sperm concentration (median, 15 x 10(6)/mL;
      range, 0 to 128 x 10(6)/mL) and total sperm count (median, 29 x 10(6)/mL; range,
      0 to 589 x 10(6)) in patients with testicular cancer than in patients with
      malignant lymphomas (sperm concentration: median, 48 x 10(6)/mL; range, 0.04 to
      250 x 10(6)/mL; sperm count: median, 146 x 10(6); range, 0.05 to 418 x 10(6)) (P
      < .001 and P < .001) and healthy men (sperm concentration: median, 48 x 10(6)/mL;
      range, 0 to 402 x 10(6)/mL; sperm count: median, 162 x 10(6); range, 0 to 1253 x
      10(6)) (P < .001 and P < .001). FSH levels were increased in men with testicular
      cancer (median, 5.7 IU/L; range, 2.0 to 27 IU/L) compared with both men with
      malignant lymphomas (median, 3.3 IU/L; range, 1.01 to 12.0 IU/L) and healthy
      controls (median, 4.1 IU/L; range, 1.04 to 21 IU/L)(P = .001 and P = .007,
      respectively). Surprisingly, we found significantly lower LH in the group of men
      with TGCC (median, 3.6 IU/L; range, 1.12 to 11.9 IU/L) than in healthy men
      (median, 4.7 IU/L; range, 1.3 to 11.9 IU/L) (P = .01). We could not detect any
      differences between men with testicular cancer and men with malignant lymphomas
      and healthy men with regard to serum levels of testosterone, SHBG, and estradiol.
      Men with testicular cancer who had increased hCG levels had significantly lower
      LH and significantly higher testosterone and estradiol than those without
      detectable hCG levels. CONCLUSION: Spermatogenesis is already impaired in men
      with testicular cancer before orchiectomy. Neither local suppression of
      spermatogenesis by tumor pressure nor a general cancer effect seems to fully
      explain this impairment. The most likely explanation is preexisting impairment of
      spermatogenesis in the contralateral testis in men with testicular cancer. The
      question of whether also a pre-existing Leydig cell dysfunction is present in men
      with testicular cancer could not be answered in this study because the tumor
      seems to have a direct effect on the Leydig cells. Men with testicular cancer had
      low LH values as compared with controls. We speculate that increased
      intratesticular level of hCG also in men without measurable serum hCG may play a
      role by exerting LH-like effects on the Leydig cells, causing increased
      testosterone and estrogen levels and low LH values in the blood.

PMID- 10071289
TI  - Prognostic significance of extent of disease in bone in patients with androgen
      independent prostate cancer.
AB  - PURPOSE: To evaluate the prognostic significance of a bone scan index (BSI) based
      on the weighted proportion of tumor involvement in individual bones, in relation
      to other factors and to survival in patients with androgen-independent prostate
      cancer. PATIENTS AND METHODS: Baseline radionuclide bone scans were reviewed in
      191 assessable patients with androgen-independent disease who were enrolled onto
      an open, randomized trial of liarozole versus prednisone. The extent of skeletal
      involvement was assessed by scoring each scan using the BSI and independently
      according to the number of metastatic lesions. The relationship of the scored
      bone involvement to other known prognostic factors was explored in single- and
      multiple-variable analyses. RESULTS: In single-variable analyses, the
      pretreatment factors found to be associated with survival were age (P = .0446),
      performance status (P = .0005), baseline prostate-specific antigen (P = .0001),
      hemoglobin (P = .0001), alkaline phosphatase (P = .0002), AST (P = .0021),
      lactate dehydrogenase (P = .0001), and treatment (P = .0098). The extent of
      osseous disease was significant using both the BSI (P = .0001) and the number of
      lesions present (P = .0001). In multiple-variable proportional hazards analyses,
      only BSI, age, hemoglobin, lactate dehydrogenase, and treatment arm were
      associated with survival. When the patient population was divided into three
      equal groups, with BSI values of < 1.4%, 1.4% to 5.1%, and > 5.1%, median
      survivals of 18.3, 15.5, and 8.1 months, respectively, were observed (P = .0079).
      CONCLUSION: The BSI quantifies the extent of skeletal involvement by tumor. It
      allows the identification of patients with distinct prognoses for stratification
      in clinical trials. Further study is needed to assess the utility of serial BSI
      determinations in monitoring treatment effects. The BSI may be particularly
      useful in the evaluation of agents for which prostate-specific antigen changes do
      not reflect clinical outcomes accurately.

PMID- 10071290
TI  - Phase I trial of docetaxel with estramustine in androgen-independent prostate
      cancer.
AB  - PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel
      when combined with oral estramustine and dexamethasone in a phase I study in
      patients with progressive metastatic androgen-independent prostate cancer.
      PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated
      (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was
      administered 1 hour before or 2 hours after meals on days 1 through 5, with
      escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated
      every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33
      for response. In the MPT patients, dose-limiting myelosuppression was reached at
      80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT
      patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six
      EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive
      measurements taken at least 2 weeks apart. The overall 50% PSA response rate was
      63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with
      bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a
      partial response. At the time of entry onto the study, 15 patients required
      narcotic analgesics for bone pain; after treatment, eight (53%) discontinued
      their pain medications. The area under the curve for docetaxel increased linearly
      from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37
      (standard deviation, 0.724), which was significantly higher than the previously
      reported values. CONCLUSION: The recommended phase II dose of docetaxel combined
      with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This
      combination is active in men with androgen-independent prostate cancer.

PMID- 10071291
TI  - Prospective randomized trial of the treatment of patients with metastatic
      melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or
      in combination with interleukin-2 and interferon alfa-2b.
AB  - PURPOSE: The combination of chemotherapy with immunotherapeutic agents such as
      interleukin-2 and interferon alfa-2b has been reported to provide improved
      treatment results in patients with metastatic melanoma, compared with the use of
      chemotherapy alone. We have performed a prospective randomized trial in patients
      with metastatic melanoma, comparing treatment with chemotherapy to treatment with
      chemoimmunotherapy. PATIENTS AND METHODS: One hundred two patients with
      metastatic melanoma were prospectively randomized to receive chemotherapy
      composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy
      followed by interferon alfa-2b and interleukin-2. Objective responses, survival,
      and toxicity in the two groups were evaluated at a median potential follow-up of
      42 months. RESULTS: In 52 patients randomized to receive chemotherapy, there were
      14 objective responses (27%), including four complete responses. In 50 patients
      randomized to receive chemoimmunotherapy, there were 22 objective responses (44%)
      (P2 = .071), including three complete responses. In both treatment groups, the
      duration of partial responses was often short, and there was a trend toward a
      survival advantage for patients receiving chemotherapy alone (P2 = .052; median
      survival of 15.8 months compared with 10.7 months). Treatment-related toxicities
      were greater in patients receiving chemoimmunotherapy. CONCLUSION: With the
      treatment regimens used in this study, the addition of immunotherapy to
      combination chemotherapy increased toxicity but did not increase survival. The
      use of combination chemoimmunotherapy regimens is not recommended in the absence
      of well-designed, prospective, randomized protocols showing the benefit of this
      treatment strategy.

PMID- 10071292
TI  - Multi-institutional melanoma lymphatic mapping experience: the prognostic value
      of sentinel lymph node status in 612 stage I or II melanoma patients.
AB  - PURPOSE: To compare the effect of pathologic sentinel lymph node (SLN) status
      with that of other known prognostic factors on recurrence and survival in
      patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS: We reviewed
      the records of 612 patients with primary cutaneous melanoma who underwent
      lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine
      the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN
      pathologic status on disease-free and disease-specific survival. RESULTS: In the
      580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN
      was positive by conventional histology in 85 patients (15%) but negative in 495
      patients (85%). SLN status was the most significant prognostic factor with
      respect to disease-free and disease-specific survival by univariate and multiple
      covariate analyses. Although tumor thickness and ulceration influenced survival
      in SLN-negative patients, they provided no additional prognostic information in
      SLN-positive patients. CONCLUSION: Lymphatic mapping and SLN biopsy is highly
      accurate in staging nodal basins at risk for regional metastases in primary
      melanoma patients and identifies those who may benefit from earlier
      lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with
      clinically negative nodes is the most important prognostic factor for recurrence.
      The information from SLN biopsy is particularly helpful in establishing
      stratification criteria for future adjuvant trials.

PMID- 10071293
TI  - Phase II study of phenylacetate in patients with recurrent malignant glioma: a
      North American Brain Tumor Consortium report.
AB  - PURPOSE: To determine the response rate, time to treatment failure, and toxicity
      of phenylacetate in patients with recurrent malignant glioma and to identify
      plasma concentrations achieved during repeated continuous infusion of this agent.
      PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated
      with phenylacetate. The schedule consisted of a 2-week continuous, intravenous
      infusion followed by a 2-week rest period (14 days on, 14 days off). A starting
      dose of 400 mg/kg total body weight per day of phenylacetate was initially used
      and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient
      dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d.
      Tumor response was assessed every 8 weeks. The National Cancer Institute common
      toxicity criteria were used to assess toxicity. Plasma concentrations achieved
      during the patients' first two 14-day infusions were assessed. RESULTS: Forty
      three patients were enrolled between December 1994 and December 1996. Of these,
      40 patients were assessable for toxicity and response to therapy. Reversible
      symptoms of fatigue and somnolence were the primary toxicities, with only mild
      hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2
      months, seven (17.5%) had stable disease, and three (7.5%) had a response defined
      as more than 50% reduction in the tumor. Median time to treatment failure was 2
      months. Thirty-five patients have died, with a median survival of 8 months.
      Pharmacokinetic data for this dose schedule showed no difference in the mean
      plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5
      and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in
      patients with recurrent malignant glioma. Further studies with this drug would
      necessitate an evaluation of a different dose schedule.

PMID- 10071294
TI  - Outcome for cancer patients requiring mechanical ventilation.
AB  - PURPOSE: To describe hospital survival for cancer patients who require mechanical
      ventilation. MATERIALS AND METHODS: A prospective, multicenter observational
      study was performed at five academic tertiary care hospitals. Demographic and
      clinical variables were obtained on consecutive cancer patients at initiation of
      mechanical ventilation, and information on vital status at hospital discharge was
      acquired. RESULTS: Our analysis was based on 782 adult cancer patients who met
      predetermined inclusion criteria. The overall observed hospital mortality was
      76%, with no statistically significant differences among the five study centers.
      Seven variables (intubation after 24 hours, leukemia, progression or recurrence
      of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence
      of disseminated intravascular coagulation, and need for vasopressor therapy) were
      associated with an increased risk of death, whereas prior surgery with curative
      intent was protective. The predictive model based on these variables had an area
      under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow
      goodness-of-fit statistics of 7.19; P = .52. CONCLUSION: This model can be used
      to estimate the probability of hospital survival for classes of adult cancer
      patients who require mechanical ventilation and can help to guide physicians,
      patients, and families in deciding goals and direction of treatment. Prospective
      independent validation in different medical settings is warranted.

PMID- 10071295
TI  - Automated collection of quality-of-life data: a comparison of paper and computer
      touch-screen questionnaires.
AB  - PURPOSE: To evaluate alternative automated methods of collecting data on quality
      of life (QOL) in cancer patients. After initial evaluation of a range of
      technologies, we compared computer touch-screen questionnaires with paper
      questionnaires scanned by optical reading systems in terms of patients'
      acceptance, data quality, and reliability. PATIENTS AND METHODS: In a randomized
      cross-over trial, 149 cancer patients completed the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version
      2.0 (EORTC QLQ-C30), and the Hospital Anxiety and Depression Scale (HADS) on
      paper and on a touch screen. In a further test-retest study, 81 patients
      completed the electronic version of the questionnaires twice, with a time
      interval of 3 hours between questionnaires. RESULTS: Fifty-two percent of the
      patients preferred the touch screen to paper; 24% had no preference. The quality
      of the data collected with the touch-screen system was good, with no missed
      responses. At the group level, the differences between scores obtained with the
      two modes of administration of the instruments were small, suggesting equivalence
      for most of the QOL scales, with the possible exception of the emotional,
      fatigue, and nausea/vomiting scales and the appetite item, where patients tended
      to give more positive responses on the touch screen. At the individual patient
      level, the agreement was good, with a kappa coefficient from 0.57 to 0.77 and
      percent global agreement from 61% to 97%. The electronic questionnaire had good
      test-retest reliability, with correlation coefficients between the two
      administrations from 0.78 to 0.95, kappa coefficients of agreement from 0.55 to
      0.90, and percent global agreement from 56% to 100%. CONCLUSION: Computer touch
      screen QOL questionnaires were well accepted by cancer patients, with good data
      quality and reliability.

PMID- 10071296
TI  - Quality of life in head and neck cancer patients: validation of the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      H&N35.
AB  - PURPOSE: The aim of this study was to define the scales and test the validity,
      reliability, and sensitivity of the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-H&N35, a
      questionnaire designed to assess the quality of life of head and neck (H&N)
      cancer patients in conjunction with the general cancer-specific EORTC QLQ-C30.
      PATIENTS AND METHODS: Questionnaires were given to 500 H&N cancer patients from
      Norway, Sweden, and the Netherlands as part of two prospective studies. The
      patients completed the questionnaires before, during (Norway and Sweden only),
      and after treatment, yielding a total of 2070 completed questionnaires. RESULTS:
      The compliance rate was high, and the questionnaires were well accepted by the
      patients. Seven scales were constructed (pain, swallowing, senses, speech, social
      eating, social contact, sexuality). Scales and single items were sensitive to
      differences between patient subgroups with relation to site, stage, or
      performance status. Most scales and single items were sensitive to changes, with
      differences of various magnitudes according to the site in question. The internal
      consistency, as assessed by Cronbach's alpha coefficient, varied according to
      assessment point and within subsamples of patients. A low overall alpha value was
      found for the speech and the senses scales, but values were higher in assessments
      of patients with laryngeal cancer and in patients with nose, sinus, and salivary
      gland tumors. Scales and single items in the QLQ-H&N35 seem to be more sensitive
      to differences between groups and changes over time than do the scales and single
      items in the core questionnaire. CONCLUSION: The QLQ-H&N35, in conjunction with
      the QLQ-C30, provides a valuable tool for the assessment of health-related
      quality of life in clinical studies of H&N cancer patients before, during, and
      after treatment with radiotherapy, surgery, or chemotherapy.

PMID- 10071297
TI  - Quality of life and performance in advanced head and neck cancer patients on
      concomitant chemoradiotherapy: a prospective examination.
AB  - PURPOSE: To prospectively evaluate performance and quality of life (QOL) in
      advanced-stage head and neck cancer (HNC) patients on a curative-intent,
      concomitant-chemoradiotherapy (CT/XRT) (twice-daily radiation, fluorouracil,
      hydroxyurea, and cisplatin) regimen aimed at improving locoregional control,
      survival, and QOL. PATIENTS AND METHODS: Sixty-four patients were assessed
      before, during, and at 3-month intervals after treatment. Standardized measures
      of QOL (Functional Assessment of Cancer Therapy-Head and Neck), performance
      (Performance Status Scale for Head and Neck Cancer Patients and Karnofsky
      Performance Status Rating Scale), and patient-reported symptoms (McMaster
      University Head and Neck Radiotherapy Questionnaire) were administered. RESULTS:
      Acute treatment toxicities were severe, with declines in virtually all QOL and
      functional domains. Marked improvement was seen by 12 months; general functional
      and physical measures returned to baseline levels of good to excellent. Although
      up to a third of the patients continued to report problems with swallowing,
      hoarseness, and mouth pain, these difficulties were present in similar magnitudes
      before treatment. The following symptoms were more frequent at 12 months: dry
      mouth (58% v 17%), difficulties tasting (32% v 8%), and soft food diet (82% v
      42%). Twelve-month diet was not related to pretreatment functioning, disease,
      treatment, or patient characteristics. Twelve-month QOL was best predicted by
      pretreatment QOL, with very little relationship to residual side effects or
      functional impairments. Small numbers of patients in four of the five disease
      sites precluded examination of outcome by site. CONCLUSION: These data support
      the feasibility of intense CT/XRT as primary treatment for advanced HNC. Results
      confirm acute toxicity but indicate that many of the treatment-related
      performance and QOL declines resolve by 12 months. The persistent inability to
      eat a full range of foods warrants further attention and monitoring.

PMID- 10071298
TI  - Recruiting minority cancer patients into cancer clinical trials: a pilot project
      involving the Eastern Cooperative Oncology Group and the National Medical
      Association.
AB  - PURPOSE: Minority accrual onto clinical trials is of significant interest to
      cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG)
      conducted a study to identify barriers and solutions to African American accrual
      onto clinical trials. METHODS: We hypothesize that the National Medical
      Association (NMA) might provide insight into ways to increase minority
      participation and that ECOG might facilitate that participation. Four sites were
      selected in which NMA chapters existed and ECOG main institutions with less than
      half of the corresponding percentage of minorities in their communities entered
      trials for 1992. Fifteen workshops were conducted using discussions and open
      ended, self-administered questionnaires. RESULTS: Seventy percent of NMA
      physicians cited mistrust of the research centers, fear of losing patients, and a
      lack of respect from ECOG institutions as the most important barriers to minority
      cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine
      percent of NMA and 43% of ECOG physicians cited a lack of information about
      specific trials. Nearly half of NMA physicians (47%) cited a lack of minority
      investigators as a barrier, compared with 4% of ECOG physicians. Solutions by
      both groups were improved communication (73%) and culturally relevant educational
      materials (40%). ECOG physicians cited more minority outreach staff as a
      potential solution (22% v 6%). NMA physicians cited increased involvement of
      referring physicians (44% v4%). CONCLUSION: NMA physicians who serve a
      significant sector of the African American population demonstrated a willingness
      to participate and work with a cooperative group effort to increase participation
      of minority patients and investigators.

PMID- 10071299
TI  - Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian
      cancer considering testing for BRCA1 and BRCA2.
AB  - PURPOSE: This study examined baseline knowledge, beliefs, and risk perceptions
      among a group of 200 women with breast and/or ovarian cancer who participated in
      a trial designed to improve decision making about genetic testing for BRCA1 and
      BRCA2. PATIENTS AND METHODS: Women were identified by self-referral, physician
      referral, and tumor registry extraction and invited to participate in a
      randomized trial in which testing for BRCA1 and BRCA2 was offered free of charge.
      Subjects completed baseline questionnaires and interviews that assessed
      knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or
      BRCA2. RESULTS: Sixty percent of women overestimated their chances of having a
      BRCA1 or BRCA2 mutation compared with estimates from a BRCA1/BRCA2 risk model.
      Women who have at least three relatives with breast or ovarian cancer were one
      third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk
      of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer
      affected relatives. Knowledge was limited about BRCA1 and BRCA2 mutations and
      cancer risk associated with gene mutations. Eighty-four percent of the women
      indicated a probable or definite interest in testing. CONCLUSION: A high
      proportion of the high-risk women in this study had knowledge deficits about
      BRCA1 and BRCA2 and overestimated their risk of having a mutation. Although some
      degree of caution should be used in generalizing the results of this study to
      practice settings, the data provide insight into the challenges clinicians will
      face in communicating with patients about cancer genetics.

PMID- 10071300
TI  - Cancer vaccines.
AB  - It has been more than 100 years since the first reported attempts to activate a
      patient's immune system to eradicate developing cancers. Although a few of the
      subsequent vaccine studies demonstrated clinically significant treatment effects,
      active immunotherapy has not yet become an established cancer treatment modality.
      Two recent advances have allowed the design of more specific cancer vaccine
      approaches: improved molecular biology techniques and a greater understanding of
      the mechanisms involved in the activation of T cells. These advances have
      resulted in improved systemic antitumor immune responses in animal models.
      Because most tumor antigens recognized by T cells are still not known, the tumor
      cell itself is the best source of immunizing antigens. For this reason, most
      vaccine approaches currently being tested in the clinics use whole cancer cells
      that have been genetically modified to express genes that are now known to be
      critical mediators of immune system activation. In the future, the molecular
      definition of tumor-specific antigens that are recognized by activated T cells
      will allow the development of targeted antigen-specific vaccines for the
      treatment of patients with cancer.

PMID- 10071301
TI  - Mechanisms of action of and resistance to antitubulin agents: microtubule
      dynamics, drug transport, and cell death.
AB  - PURPOSE: To analyze the available data concerning mechanisms of action of and
      mechanisms of resistance to the antitubulin agents, vinca alkaloids and taxanes,
      and more recently described compounds. DESIGN: We conducted a review of the
      literature on classic and recent antitubulin agents, focusing particularly on the
      relationships between antitubulin agents and their intracellular target, the
      soluble tubulin/microtubule complex. RESULTS AND CONCLUSION: Although it is
      widely accepted that antitubulin agents block cell division by inhibition of the
      mitotic spindle, the mechanism of action of antitubulin agents on microtubules
      remains to be determined. The classic approach is that vinca alkaloids
      depolymerize microtubules, thereby increasing the soluble tubulin pool, whereas
      taxanes stabilize microtubules and increase the microtubular mass. More recent
      data suggest that both classes of agents have a similar mechanism of action,
      involving the inhibition of microtubule dynamics. These data suggest that vinca
      alkaloids and taxanes may act synergistically as antitumor agents and may be
      administered as combination chemotherapy in the clinic. However, enhanced myeloid
      and neurologic toxicity, as well as a strong dependence on the sequence of
      administration, presently exclude these combinations outside the context of
      clinical trials. Although the multidrug resistance phenotype mediated by Pgp
      appears to be an important mechanism of resistance to these agents, alterations
      of microtubule structure resulting in altered microtubule dynamics and/or altered
      binding of antitubulin agents may constitute a significant mechanism of drug
      resistance.

PMID- 10071302
TI  - RAS and leukemia: from basic mechanisms to gene-directed therapy.
AB  - PURPOSE AND DESIGN: The purpose of this review is to provide an overview of the
      literature linking Ras signaling pathways and leukemia and to discuss the
      biologic and potential therapeutic implications of these observations. A search
      of MEDLINE from 1966 to October 1998 was performed. RESULTS: A wealth of data has
      been published on the role of Ras pathways in cancer. To be biologically active,
      Ras must move from the cytoplasm to the plasma membrane. Importantly, a
      posttranslational modification--addition of a farnesyl group to the Ras C
      terminal cysteine--is a requisite for membrane localization of Ras. Farnesylation
      of Ras is catalyzed by an enzyme that is designated farnesyltransferase.
      Recently, several compounds have been developed that can inhibit farnesylation.
      Preclinical studies indicate that these molecules can suppress transformation and
      tumor growth in vitro and in animal models, with little toxicity to normal cells.
      CONCLUSION: An increasing body of data suggests that disruption of Ras signaling
      pathways, either directly through mutations or indirectly through other genetic
      aberrations, is important in the pathogenesis of a wide variety of cancers.
      Molecules such as farnesyl transferase inhibitors that interfere with the
      function of Ras may be exploitable in leukemia (as well as in solid tumors) as
      novel antitumor agents.

PMID- 10071303
TI  - American Society of Clinical Oncology 1998 update of recommended breast cancer
      surveillance guidelines.
AB  - OBJECTIVE: To determine an effective, evidence-based, postoperative surveillance
      strategy for the detection and treatment of recurrent breast cancer. Tests are
      recommended only if they have an impact on the outcomes specified by American
      Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL
      INTERVENTION: All tests described in the literature for postoperative monitoring
      were considered. In addition, the data were critically evaluated to determine the
      optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall
      and disease-free survival, quality of life, toxicity reduction, and secondarily
      cost-effectiveness. EVIDENCE: A search was performed to determine all relevant
      articles published over the past 20 years on the efficacy of surveillance testing
      for breast cancer recurrence. These publications comprised both retrospective and
      prospective studies. VALUES: Levels of evidence and guideline grades were rated
      by a standard process. More weight was given to studies that tested a hypothesis
      directly relating testing to one of the primary outcomes in a randomized design.
      BENEFITS, HARMS, AND COSTS: The possible consequences of false-positive and 
      negative tests were considered in evaluating a preference for one of two tests
      providing similar information. Cost alone was not a determining factor.
      RECOMMENDATIONS: The attached guidelines and text summarize the updated
      recommendations of the ASCO breast cancer expert panel. Data are sufficient to
      recommend monthly breast self-examination, annual mammography of the preserved
      and contralateral breast, and a careful history and physical examination every 3
      to 6 months for 3 years, then every 6 to 12 months for 2 years, then annually.
      Data are not sufficient to recommend routine bone scans, chest radiographs,
      hematologic blood counts, tumor markers (carcinoembryonic antigen, cancer antigen
      [CA] 15-5, and CA 27.29), liver ultrasonograms, or computed tomography scans.
      VALIDATION: The recommendations of the breast cancer expert panel were evaluated
      and supported by the ASCO Health Services Research Committee reviewers and the
      ASCO Board of Directors.

PMID- 10071304
TI  - Unusual manifestations of B-cell disorders. Case 1: multiple myeloma with
      predominant phalangeal involvement.

PMID- 10071305
TI  - Unusual manifestations of B-cell disorders. Case 2: chronic lymphocytic leukemia
      presenting with cutaneous lesions.

PMID- 10071306
TI  - Low-dose chemotherapy with vinblastine and methotrexate in childhood desmoid
      tumors.

PMID- 10071307
TI  - Prostate-specific antigen decline after withdrawal of low-dose megestrol acetate.

PMID- 10071308
TI  - Detrimental effects of prechemotherapy filgrastim.

PMID- 10071309
TI  - Mucocutaneous reactions to chemotherapy.
AB  - Chemotherapeutic agents are a widely used treatment modality. Side effects range
      from common to unusual and may be confused with other cutaneous sequelae of
      oncologic treatment. The goal of this communication is to elaborate on previous
      descriptions of the cutaneous manifestations of chemotherapeutic treatment and to
      discuss more recent findings. LEARNING OBJECTIVE: At the conclusion of this
      learning activity, participants should be able to generate a differential
      diagnosis of possible etiologies for varying patterns of cutaneous involvement in
      patients receiving chemotherapy and identify the various cutaneous side effects
      of chemotherapeutic treatment. In addition, they should be able to distinguish
      life-threatening side effects that require immediate management from more benign
      manifestations of chemotherapeutic treatment.

PMID- 10071310
TI  - Long-term effectiveness and side effects of carbon dioxide laser resurfacing for
      photoaged facial skin.
AB  - BACKGROUND: Laser resurfacing has been used for treatment of photoaged facial
      skin since late 1993. Very few long-term follow-up studies regarding the
      effectiveness and side effects of this procedure have been reported. METHOD:
      Patients who received carbon dioxide laser resurfacing for facial photoaging and
      wrinkling from Dec 17, 1993, to Nov 30, 1996, were followed up with clinical
      evaluation and patient questionnaires. Histologic study was also performed in 10
      representative patients who had had preoperative biopsies. All treatments were
      performed by 2 experienced laser surgeons (R. E. F. and M. P. G.). RESULTS: One
      hundred four patients were examined and interviewed with an average 24-month
      postoperative follow-up (range 12 to 44 months). We observed high patient
      satisfaction ratings and significant persistence of wrinkle score improvement.
      Long-term histologic features confirmed the long-lasting nature of the clinical
      improvement and demonstrated continuing, progressive improvement in solar
      clastosis deep in the dermis for an average follow-up period of 2 years.
      Prolonged use of topical tretinoin (retinoic acid) postoperatively may contribute
      to continued improvement. The incidence of long-term side effects, including
      pigmentary changes and scarring, was generally very low and these side effects
      were usually not noticed by the patients. CONCLUSION: Improvement from cutaneous
      laser resurfacing has persisted for an average 24-month postoperative period with
      a low incidence of side effects. Hypopigmentation is the most common long-term
      side effect and appears to be related to the degree of pre-existing photodamage
      as it contrasts with the newly healed undamaged skin.

PMID- 10071311
TI  - Epidermal grafts for treatment of stable and progressive vitiligo.
AB  - BACKGROUND: Previous reports have shown the effectiveness of epidermal grafts for
      patients with stable vitiligo. OBJECTIVE: Our purpose was to evaluate the
      effectiveness and complications of epidermal grafts in patients with stable and
      progressive vitiligo and to compare the results in both groups. METHODS:
      Epidermal grafting with suction blisters was performed in 40 patients with
      vitiligo (26 stable and 14 progressive). The grafted sites and donor sites were
      examined for repigmentation for longer than 3 months, up to 2.5 years. RESULTS:
      Complete repigmentation was observed in 19 patients with stable (73.1%) and 10
      with progressive vitiligo (71.4%). Of the 29 patients who experienced complete
      repigmentation, we noted recurrences in 2 patients with stable disease (10.5%)
      and 4 with progressive disease (40%). CONCLUSION: Although patients with
      progressive vitiligo showed more frequent recurrence than those with stable
      disease, epidermal grafting may be an effective treatment not only for stable
      vitiligo but also for progressive vitiligo.

PMID- 10071312
TI  - Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489
      patients.
AB  - BACKGROUND: Although a number of studies have documented the long-term survival
      of patients with cutaneous T-cell lymphoma (CTCL), none have provided data as to
      the relative survival of all 4 skin stages. OBJECTIVE: We document survival of
      CTCL patients by T stage relative to that of an age-, sex-, and race-matched
      population. METHODS: The survival of 489 patients with CTCL registered since 1957
      was compared with that of a California control population. RESULTS: For stage T1
      (< 10% skin involved) there was no significant difference between the observed
      and expected survivals. For the other 3 stages the observed survival was
      significantly inferior to that of the expected survival (P = .002). At 10 years
      the relative survivals were: T2 (10% or more skin involved) 67.4%, T3 (tumor
      stage) 39.2%, T4 (generalized erythroderma) 41.0%. T2 plaque stage patients had
      an inferior relative survival (P = .001), whereas T2 patch stage patients did
      not. Lymphadenopathy had an unfavorable impact on prognosis. There was a strong
      trend toward diagnosing CTCL at an earlier stage in more recent years. We
      estimate that from 15% to 20% of our patients died of CTCL or related
      complications. CONCLUSION: The relative survival of CTCL patients worsens with
      increasing skin stage, although stages T3 and T4 had closely similar survivals.
      The great majority of patients with CTCL do not die of their disease.

PMID- 10071313
TI  - The gatekeeper model is inefficient for the delivery of dermatologic services.
AB  - BACKGROUND: Gatekeeper-paradigm managed care systems may discourage the use of
      dermatologists in the management of skin conditions by limiting direct access.
      This may limit the quality of care patients with skin disorders receive and may
      be an inefficient use of medical resources. OBJECTIVE: The purpose of this study
      was to determine the likelihood that patients with dermatologic conditions who
      see a primary care provider will be referred to a dermatologist. METHODS: Data on
      the disposition of outpatient visits to primary care physicians for one and only
      one dermatologic diagnosis were obtained from the 1990-1994 National Ambulatory
      Medical Care Survey. These data were used in an econometric model to estimate the
      likelihood of referral to a dermatologist for an episode of care. RESULTS: Of all
      visits for a single dermatologic diagnosis, 39% were to primary care physicians.
      The disposition of referral was more common for these dermatology-related visits
      than for all office visits to primary care physicians (5.8% vs 4.5%, P < .001).
      The most frequent diagnoses associated with referral were common dermatologic
      problems, not rare disorders. The number of visits per episode of care was highly
      dependent on the assumptions of the analysis, resulting in estimate ranges for
      referral rates per episode between 6.8% and 18.5% for pediatricians, 8.2% and 23%
      for family and general practitioners, and 16.6% and 46.5% for internists.
      CONCLUSION: The relative difficulty for primary care providers of managing skin
      problems is reflected by their frequent need to refer patients with common skin
      problems and by the greater likelihood of referral for skin disorders than for
      other medical conditions. The high rates of referral per episode of care supports
      the cost-effectiveness of direct access to dermatologists.

PMID- 10071314
TI  - Helicobacter pylori eradication treatment reduces the severity of rosacea.
AB  - BACKGROUND: A higher prevalence of Helicobacter pylori infection in rosacea
      patients than in healthy controls has been reported. OBJECTIVE: The aim of this
      study was to investigate the effect of H. pylori eradication therapy in patients
      with rosacea. METHODS: Twenty-five rosacea patients and 87 age- and sex-matched
      healthy controls were included in this study. We detected IgG and IgA antibodies
      against H. pylori in both groups. An upper gastrointestinal endoscopy and a rapid
      urease test were performed on the 13 patients with rosacea who accepted this
      procedure. Amoxicillin 500 mg 3 times daily, metronidazole 500 mg 3 times daily,
      and bismuth subcitrate 300 mg 4 times daily were administered to patients
      positive for H. pylori. The severity of rosacea was scored before and after
      treatment. RESULTS: There was no statistical difference in seropositivity in
      either group. In H. pylori-positive rosacea patients there was a significant
      decrease in the severity of rosacea at the end of the treatment as compared with
      the initial scores. CONCLUSION: Our findings suggest that H. pylori may be
      involved in rosacea and that eradication treatment may be beneficial.

PMID- 10071315
TI  - In vivo study of skin mechanical properties in patients with systemic sclerosis.
AB  - BACKGROUND: Measurements of skin elasticity are more sensitive than the skin
      severity score and appropriate for evaluation of sclerodermatous skin. OBJECTIVE:
      Our purpose was to investigate the mechanical properties of the skin in patients
      with systemic sclerosis depending on the stage of the disease. METHODS: Seventeen
      patients, 8 with edematous phase and 9 with indurative phase of skin involvement,
      and 16 healthy subjects were studied. Clinical scoring of skin thickness and
      measurements of skin elasticity with a noninvasive suction device (Cutometer)
      were performed over 11 anatomic regions. RESULTS: Edematous phase was
      characterized by significantly lower immediate distention (Ue) and final
      distention (Uf), and higher viscoelastic to elastic ratio (Uv/Ue) of the skin
      compared with indurative phase, except for the forehead (8 mm probe). The changes
      in skin mechanical parameters for fingers were identical in both phases. Low
      values of skin distensibility correlated with severe skin thickness or hidebound
      skin. Results were influenced by body site and by the diameter of measuring probe
      used. CONCLUSION: The noninvasive method applied is suitable for objective and
      quantitative monitoring of skin involvement in patients with systemic sclerosis.

PMID- 10071316
TI  - Chronic idiopathic urticaria: comparison of the clinical features of patients
      with and without anti-FcepsilonRI or anti-IgE autoantibodies.
AB  - BACKGROUND: Previous studies defining the clinical features of patients with
      chronic idiopathic urticaria (CIU) were performed before the identification of
      functional autoantibodies against FcepsilonRI and/or IgE, now known to be present
      in approximately 30% of patients with CIU. OBJECTIVE: Our purpose was to
      determine whether there are differences between patients with and those without
      autoantibodies in the clinical features or severity of CIU. METHODS: The clinical
      features of 107 patients with CIU were evaluated prospectively. Patients were
      identified as having functional autoantibodies on the basis of the serum-evoked
      histamine release in vitro from the basophils of 2 healthy donors. RESULTS:
      Patients with autoantibodies (31%) had more wheals (P = .005), a wider
      distribution of wheals (P = .009), higher itch scores for the most severe
      episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum
      IgE levels (P < .0005) than patients without autoantibodies. CONCLUSION: The
      presence of autoantibodies indicates a subset of patients with more severe CIU.

PMID- 10071317
TI  - Penile lichen sclerosus et atrophicus treated with clobetasol dipropionate 0.05%
      cream: a retrospective clinical and histopathological study.
AB  - BACKGROUND: Treatment with clobetasol propionate 0.05% cream is effective against
      lichen sclerosus et atrophicus (LSA) of the vulva. OBJECTIVE: The purpose of this
      study was to retrospectively evaluate whether clinical and histologic responses
      to topical clobetasol can be accomplished in penile LSA. METHODS: A self
      assessment questionnaire was obtained from 22 men with LSA, and a clinical
      examination was performed in 21 of them. Biopsy specimens from 15 cases were
      compared before and after treatment. RESULTS: Itching, burning, pain,
      dyspareunia, phimosis, and dysuria decreased significantly (P < .001 to .05)
      after 1 to 2 daily applications, for a mean of 7.1 weeks (2-16 weeks). Additional
      operation for phimosis was required in 6 of the 22 men. All histologic LSA
      criteria were significantly (P < .01 to .05) reduced after treatment. CONCLUSION:
      Topical treatment of penile LSA with clobetasol propionate represents a safe and
      effective therapy with no risk of epidermal atrophy but with some potential for
      triggering latent infections, most importantly human papillomavirus.

PMID- 10071318
TI  - Plasmapheresis as an adjunct treatment in toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, progressive disease
      characterized by the sudden onset of skin necrosis. It is frequently associated
      with systemic involvement and has a high rate of morbidity and mortality.
      Standard therapy includes meticulous wound care, fluid replacement, and
      nutritional support in an intensive care setting. OBJECTIVE: We evaluated the
      outcomes of patients treated in a burn unit for TEN over a 9-year period and
      compared the outcomes of a subset of patients treated with plasmapheresis with
      those managed by conventional means. METHODS: The records of 16 patients with a
      diagnosis of TEN obtained from a computerized database were reviewed. Parameters
      recorded included extent of body surface area involvement and number of mucous
      membranes involved at admission, complications such as sepsis or need for
      mechanical ventilation, length of stay, and disposition. RESULTS: Sixteen
      patients were included in this study. Ten were treated with conventional support
      measures alone. Six were treated with plasmapheresis. The average age was 42.4
      years; the male/female ratio was 1:2.2. Sulfamethoxazole/trimethoprim was
      implicated in causation in 6 patients. The average extent of involvement on
      admission in all patients was 51.5% total body surface area. The average length
      of stay in all patients was 14.8 days. Eight patients (50%) were discharged home,
      4 (25%) were discharged to a rehabilitation facility, and 4 (25%) died (2 of
      sepsis, 2 of cardiopulmonary arrest). None of the plasmapheresis-treated patients
      died. CONCLUSION: Plasmapheresis is a safe intervention in extremely ill TEN
      patients and may reduce the mortality in this severe disease. Prospective studies
      are needed to further define its usefulness.

PMID- 10071319
TI  - Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical
      and histopathologic study of 6 cases.
AB  - BACKGROUND: Few case series describing Dowling-Degos disease (DDD) have been
      reported. OBJECTIVE: Our purpose was to review the clinical and histopathologic
      findings in DDD. METHODS: We reviewed the clinical and histopathologic findings
      in 6 patients with DDD who were evaluated at the Mayo Clinic. RESULTS: In
      addition to the typical flexural pigmented reticulate macules, comedo-like
      lesions on the back or neck or both were present in all 6 patients; 3 patients
      had pitted perioral scars, and 3 patients reported pruritus of affected flexural
      areas. Five patients were female, 5 patients had onset of pigmentation before age
      24 years, and 3 patients had a family history of DDD. One patient had additional
      pigmentation involving the dorsum of the hands and proximal nailfolds and
      fingernail dystrophy. Histopathologically, pigmented rete ridge elongation with
      thinning of suprapapillary epithelium, dermal melanosis, and perivascular
      lymphohistiocytic infiltration were consistently observed. CONCLUSION: Comedo
      like lesions, pruritus, and pitted perioral scars are common features in
      association with the reticulate flexural pigmentation. Histopathologically,
      pigmented rete ridge elongation and dermal melanosis of biopsy specimens from
      flexural areas are seen.

PMID- 10071320
TI  - Extraparotid Warthin's tumor.
AB  - Warthin's tumor (papillary cystadenoma lymphomatosum) is a well-known benign
      tumor of the parotid gland. Extraparotid tumors occasionally arise in the
      cervical region, where they may well be seen by the dermatologist. The following
      is a case report of an extraparotid Warthin's tumor encountered in a dermatology
      practice, with a review of the important clinical and histopathologic features of
      this tumor.

PMID- 10071321
TI  - Three new cases of transient bullous dermolysis of the newborn.
AB  - We present 3 new patients with transient bullous dermolysis of the newborn
      (TBDN), which is a form of dystrophic epidermolysis bullosa. TBDN may be
      diagnosed by electron microscopy showing a sublamina densa cleavage;
      immunofluorescence antigenic mapping demonstrating bullous pemphigoid antigen,
      laminin- 1, and type IV collagen along the epidermal roof of subepidermal clefts;
      and indirect immunofluorescence with monoclonal antibodies revealing
      intraepidermal type VII collagen. Although intraepidermal type VII collagen has
      been reported in other forms of dystrophic epidermolysis bullosa, we believe that
      the presence of type VII collagen in a striking intraepidermal granular array is
      a finding unique to TBDN. Our cases demonstrate the importance of
      immunodermatologic studies in the diagnosis of bullous disorders that are seen at
      birth because accurate diagnosis carries prognostic implications. This variant of
      epidermolysis bullosa, in contrast to other forms of dystrophic epidermolysis
      bullosa, is a benign, self-limited disease.

PMID- 10071322
TI  - Surgical pearl: versatile paper clip comedo extractor for acne surgery.

PMID- 10071323
TI  - Disseminated superficial actinic porokeratosis: treatment with topical
      tacalcitol.
AB  - Disseminated superficial actinic porokeratosis is characterized by multiple,
      brown, annular, keratotic lesions that develop predominantly on the extensor
      surfaces of the legs and arms during the third and fourth decades of life. No
      ideal treatment of disseminated superficial actinic porokeratosis has been found.
      We describe a patient with this condition whose skin lesions responded to topical
      tacalcitol.

PMID- 10071324
TI  - Increased dermal angiogenesis after low-intensity laser therapy for a chronic
      radiation ulcer determined by a video measuring system.
AB  - Acute and chronic radiation-induced dermatitis can occur after high doses of
      ionizing radiation of the skin. We describe a patient with a long-lasting
      radiotherapy-induced ulcer that healed after low-intensity laser therapy. A video
      measuring system was used to determine the number of dermal vessels in the ulcer
      before and after laser treatment. We found a statistically significant increase
      in the number of dermal vessels after low-intensity laser therapy in both the
      central and marginal parts of the ulcer compared with its pretreatment status.

PMID- 10071325
TI  - Linear IgA bullous dermatosis in a patient with chronic renal failure: response
      to intravenous immunoglobulin therapy.
AB  - Linear IgA bullous dermatosis is a blistering disease with a heterogeneous
      clinical manifestation, characterized by deposition of IgA along the basement
      membrane zone of perilesional skin on direct immunofluorescence. We describe a
      patient with chronic renal failure who experienced linear IgA bullous dermatosis.
      Long-term administration of intravenous immunoglobulin therapy was associated
      with clinical remission lasting more than 12 months.

PMID- 10071326
TI  - Twenty-nail dystrophy and vitiligo: a rare association.
AB  - The term twenty-nail dystrophy (TND) of childhood has evolved since its initial
      description in 1977. TND has also been reported in adults, and many clinical as
      well as histopathologic associations have been described. We describe the third
      case of a rare association of TND with vitiligo in a 10-year-old girl.

PMID- 10071327
TI  - Nodular fasciitis: response to intralesional corticosteroids.
AB  - Nodular fasciitis is one of the more common soft-tissue lesions, frequently
      presenting as a rapidly enlarging subcutaneous mass on the arm. Management is
      usually surgical excision; however, large infiltrative lesions may be difficult
      to manage. We describe a patient in whom intralesional corticosteroid injections
      provided rapid resolution.

PMID- 10071328
TI  - Pseudoporphyria induced by nabumetone.
AB  - Nabumetone is a nonsteroidal anti-inflammatory drug, which has only rarely been
      associated with photosensitivity. We report a case of bullous lesions arising
      over photoexposed areas in a patient treated with nabumetone.

PMID- 10071329
TI  - Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a
      patient receiving phenobarbital.
AB  - Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that most often
      appears as an adverse reaction to a medication. There have been 21 reported cases
      of atypical erythema multiforme, toxic epidermal necrolysis, and SJS arising in
      patients receiving radiation therapy in addition to phenytoin, phenobarbital, or
      carbamazepine. We report the second case of SJS resulting from concomitant
      phenobarbital and radiation therapy, in which the eruption was limited to the
      sites of radiation, which were multiple.

PMID- 10071330
TI  - Sunscreens and vitamin D levels.

PMID- 10071331
TI  - Chevron nail/herringbone nail.

PMID- 10071332
TI  - Chevron nail.

PMID- 10071333
TI  - Abbrevophilia.

PMID- 10071334
TI  - Possible hazard to patients from immersion oil used for epiluminescence
      microscopy.

PMID- 10071335
TI  - Therapeutic failure of high-dose intravenous immunoglobulin in pemphigus
      vulgaris.

PMID- 10071336
TI  - Hematopathology: integration of morphologic features and biologic markers for
      diagnosis.
AB  - The Revised European-American Classification of Lymphoid Neoplasms (REAL)
      represented a new paradigm for the classification of lymphomas. Although earlier
      classification schemes relied strictly on morphologic features or immunophenotype
      for the definition of diagnostic categories, the REAL classification emphasized
      that each disease was a distinct entity, defined by a constellation of clinical
      and laboratory features, i.e., morphologic and genetic features, immunophenotype,
      clinical presentation, and course. It also noted that the site(s) of presentation
      were often a signpost for important underlying biologic distinctions. The
      inclusion of clinical criteria for the definition of disease entities was one of
      the more novel aspects of the REAL classification. These principles of
      classification of lymphomas and leukemias also have an impact on diagnostic
      hematopathology. The REAL classification stresses that diagnoses are based on a
      multiparameter approach. Although morphologic features alone might suffice for
      some diagnoses, diagnostic accuracy and reproducibility are enhanced when
      immunophenotypic and genetic studies are also used. In addition, adequate
      clinical information is essential for some diagnoses, in particular the mature T
      cell lymphomas and leukemias. The proposed World Health Organization
      classification of lymphoid and hematopoietic neoplasms incorporates these
      principles of classification and diagnosis.

PMID- 10071337
TI  - Microscopic mimicry of lymphomas: diagnostic pitfalls.
AB  - A common, critical challenge for the pathologist is the distinction between
      lymphoma and lymphoma simulators. Ancillary studies are effective in making this
      distinction and should be used in descending order of their likely reliability
      according to the particular differential diagnostic consideration at hand.
      Clinical case information is essential to avoid misinterpretation. Lymphoma
      simulators can be grouped into several major categories: nonlymphoid neoplasms,
      usually high-grade, simulating high-grade lymphomas; chronic lymphoid
      hyperplasias simulating low-grade lymphomas; and acute lymphoid hyperplasias
      simulating high-grade lymphomas.

PMID- 10071338
TI  - Small B-cell lymphomas of the lymph nodes and spleen: practical insights to
      diagnosis and pathogenesis.
AB  - As defined in the proposed World Health Organization classification of neoplastic
      diseases of the hematopoietic and lymphoid tissues, the small B-cell lymphomas
      include B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma, mantle
      cell lymphoma, follicular lymphoma, marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT) type, nodal marginal zone lymphoma,
      lymphoplasmacytic lymphoma, and splenic marginal zone B-cell lymphoma. These
      neoplasms are recognized mostly on the basis of their histopathologic features,
      but ancillary studies are useful in confirming and sometimes making the
      diagnosis. Clinically, the small B-cell lymphomas of lymph nodes and spleen (but
      not those of MALT type) are usually disseminated at diagnosis and considered
      incurable. With the exception of mantle cell lymphoma, however, they are
      generally indolent. The small B-cell lymphomas are among the best examples of how
      malignant lymphomas can be related to the normal immune system. Although
      uncertainties exist, these lymphomas are generally considered the neoplastic
      equivalents of normal B-cell compartments. From a molecular perspective, mantle
      cell and follicular lymphomas are the best characterized. In both cases, there
      are characteristic chromosomal translocations involving the immunoglobulin heavy
      chain and the cyclin D1 or bcl-2 genes, respectively, that are probably followed
      by additional molecular events leading to overt neoplasia. Variable proportions
      of the small B-cell lymphomas undergo transformation that might be associated
      with abnormalities in tumor suppressor genes / cell cycle regulatory proteins.
      After a brief review of normal B-cell development, the major small B-cell
      lymphomas (except for those of MALT type) will be discussed in terms of their
      morphologic features, immunophenotype (including paraffin-section
      immunostaining), genotype, karyotype, and clinical features, including disease
      evolution.

PMID- 10071339
TI  - Chronic lymphoid leukemias and lymphoproliferative disorders.
AB  - Chronic lymphoproliferative disorders (CLPDs) are derived from the clonal
      proliferation of cytologically and immunophenotypically mature B or T cells.
      Although overlap is prominent, the CLPDs can generally be segregated into
      leukemias (predominant blood and bone marrow manifestations) and lymphomas
      (predominant extramedullary manifestations). This review discusses the leukemic
      processes, with emphasis placed on the blood and bone marrow features of these
      disorders. Many distinct types of B-cell and T-cell CLPDs have been described,
      and the classification of CLPDs requires the integration of morphologic features,
      immunophenotype, and clinical information; genotypic analyses might provide
      prognostic and biologic information. The various classification systems for the
      CLPDs will be presented, as well as a discussion of specific disease types,
      emphasizing those most commonly encountered in clinical practice.

PMID- 10071340
TI  - Gastrointestinal lymphomas of T- and B-cell types.
AB  - Gastrointestinal lymphomas comprise a group of distinctive clinicopathological
      entities of B- or T-cell type, with primary gastrointestinal Hodgkin's disease
      being extremely uncommon. Most low-grade B-cell gastrointestinal lymphomas are of
      mucosa-associated lymphoid tissue (MALT) type, so called because they
      recapitulate the features of MALT rather than those of lymph nodes.
      Paradoxically, however, most MALT lymphomas arise in the stomach, which normally
      contains no organized lymphoid tissue. Gastric MALT lymphomas appear to arise in
      MALT acquired as a reaction to infection of the stomach by Helicobacter pylori
      and their growth can be inhibited by eradication of this organism from the
      stomach. Low-grade MALT lymphomas, which usually have a very favorable clinical
      course, may undergo high-grade transformation but high-grade diffuse large B-cell
      lymphomas may also arise de novo. Immunoproliferative small intestinal disease
      (IPSID) is a special form of MALT lymphoma characterized by synthesis of alpha
      heavy-chain immunoglobulin and a restricted geographic distribution. Other B-cell
      lymphomas that tend to arise in the gastrointestinal tract include mantle cell
      lymphoma, which presents as lymphomatous polyposis, Burkitt's lymphoma, and B
      cell lymphomas associated with immunodeficiency states. Enteropathy (celiac
      disease)-associated T-cell lymphoma (EATL) is the most common primary
      gastrointestinal T-cell lymphoma This is a clinically aggressive tumor that
      arises from the intraepithelial T-cell population.

PMID- 10071341
TI  - Hodgkin's disease: classification and differential diagnosis.
AB  - During 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.
      Hodgkin's disease is thus a true lymphoma, deserving of a name change to
      Hodgkin's lymphoma (HL). On the basis of a combination of immunophenotype and
      morphologic features, the Revised European-American classification system
      recognizes two main types of HL: classical types (nodular sclerosis, mixed
      cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular
      lymphocyte-predominant type. These two types probably are distinct biologic
      entities. The immunophenotype and genetic features of the classical HL and the
      nodular lymphocyte-predominant type 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, i.e.,
      anaplastic large-cell lymphoma, T-cell type, and T-cell/histiocyte-rich large B
      cell lymphoma. Epstein-Barr virus has been detected in approximately 40% of the
      cases of classical HL, and it is clonal; this suggests that this virus might play
      a role in the pathogenesis of at least some types of HL. Alternatively, its
      presence might simply reflect the prevalence of Epstein-Barr virus-infected B
      cells in the individual. Despite the advances of the past 10 years, many
      questions remain to be answered; these will provide the challenges of the next
      decade.

PMID- 10071342
TI  - Peripheral T-cell and NK-cell neoplasms: an integrated approach to diagnosis.
AB  - Peripheral T-cell and NK-cell neoplasms account for only 10% of all non-Hodgkin's
      lymphomas, but they commonly pose great difficulties in diagnosis and
      classification. This article addresses the distinction between peripheral T-cell
      or NK-cell lymphoma and reactive lymphoid hyperplasia, the importance of
      recognition of the T-cell or NK-cell lineage for a lymphoma; and the importance
      of classification of a peripheral T- or NK-cell lymphoma. To solve these
      problems, it is imperative to adopt an integrated approach, taking the clinical
      features, morphologic findings, immunohistochemical profile, and/or genetic data
      into consideration.

PMID- 10071343
TI  - Immunodeficiency-associated lymphoproliferative disorders.
AB  - The incidence of lymphoproliferative disease is significantly higher in
      individuals who have congenital, acquired, or iatrogenically induced
      immunodeficiency. The immunodeficiency-associated lymphoproliferative disorders
      are clinically and pathologically heterogeneous, are of variable clonal
      composition, and vary according to the immunodeficiency syndrome. Nonetheless,
      they share several features, including frequent origination in or involvement of
      extranodal sites, diffuse aggressive histology, B-cell lineage derivation,
      association with the Epstein-Barr virus (EBV), and, often, rapid clinical
      progression. Reactive and atypical lymphoid hyperplasias and malignant lymphomas
      occur in association with congenital (primary) immunodeficiency. Post
      transplantation lymphoproliferative disorders are often comprised of a
      polymorphic cell population, making it difficult to identify their benign or
      malignant nature by histopathologic criteria alone. Recent studies suggest that
      they are divisible into plasmacytic hyperplasias, polymorphic lymphoproliferative
      disorders, and malignant lymphomas. The plasmacytic hyperplasias are polyclonal
      and generally regress spontaneously following withdrawal of immunosuppression.
      The malignant lymphomas are monoclonal, possess a variety of genetic alterations,
      and generally progress despite aggressive therapy. The polymorphic
      lymphoproliferative disorders are also monoclonal but display variable clinical
      behavior, their progression apparently correlating with bcl-6 gene mutation. Non
      Hodgkin's lymphoma (NHL) is the second most common AIDS-related neoplasm and an
      AIDS-defining illness. AIDS-related NHLs are divisible by anatomic site of origin
      into systemic (nodal/extra nodal), primary central nervous system, and body
      cavity-based (primary effusion) lymphomas; and by histopathology into Burkitt's
      and Burkitt's-like lymphoma, large cell lymphoma, and large cell immunoblastic
      (plasmacytoid) lymphoma More than 90% are monoclonal B-cell neoplasms. The
      primary effusion lymphomas contain the Kaposi's sarcoma-associated herpesvirus.
      Multiple molecular pathways appear to operate in AIDS lymphomagenesis and some
      may be preferentially associated with specific histopathologic categories or
      anatomic sites of origin. In conclusion, the immunodeficiency-associated
      lymphoproliferative disorders often represent a significant diagnostic problem
      requiring correlative analysis of the clinical behavior of the patient with the
      histopathology, immunophenotype, clonal composition, viral content, and genetic
      alterations of the lymphoproliferative disorder. They also represent an important
      biological model for studying the development and progression of lymphoid
      neoplasia

PMID- 10071344
TI  - Acute leukemias: a paradigm for the integration of new technologies in diagnosis
      and classification.
AB  - Acute leukemias (involving the myeloid and lymphoid lineages) and the related
      myelodysplastic and myeloproliferative syndromes are an extremely heterogeneous
      group of clonal neoplastic disorders. Traditionally, these diseases were
      classified solely by morphologic and cytochemical criteria, as originally
      championed in the 1976 French-American-British Group proposal. Since 1976,
      however, phenomenal scientific advances have provided new insights into the
      biology and genetics of the acute leukemias and
      myeloproliferative/myelodysplastic diseases. Immunophenotyping approaches have
      begun to supplant more traditional cytochemical assays for lineage determination,
      and cytogenetic and molecular genetic studies led to the identification and
      cloning of the genes involved in a large number of the recurrent genetic
      abnormalities in these diseases. New automated molecular technologies, reviewed
      in this article, now allow rapid and sensitive detection of these genetic
      abnormalities in leukemic cells. Such immunophenotyping and molecular genetic
      information is now considered crucial for both diagnostic and therapeutic
      decision-making. As our scientific knowledge and diagnostic sophistication
      increases, classification schemes for these disorders based solely on morphologic
      features are increasingly seen as unsatisfactory. This review highlights progress
      in the development of new morphologic classification schemes for the acute
      leukemias that integrate critical clinical, biologic, and genetic features.

PMID- 10071345
TI  - Correspondence re: Fukunaga M, Ushigome S. Epithelial metaplastic changes in
      ovarian endometriosis. Mod Pathol 1998;11:784-8.

PMID- 10071346
TI  - Liver transplantation for hepatocellular carcinoma in patients without underlying
      liver disease: a systematic review.
AB  - Liver resection is the treatment of choice for hepatocellular carcinoma (HCC)
      occurring in the absence of underlying chronic liver disease. Orthotopic liver
      transplantation (OLT) is reserved for patients with unresectable disease but
      remains controversial. The aim of this study was to review the published
      literature on OLT for HCC in patients without coexisting chronic liver disease. A
      Medline-based search identified 126 patients reported in 16 papers over the last
      32 years. One third had fibrolamellar HCC (FL-HCC), and two thirds had non-FL
      HCC. Recurrence data were given in 55 patients of whom 27 had tumor recurrence.
      Seventy-five percent of the recurrences occurred within the first 2 years after
      OLT, although recurrences were reported up to 72 months after OLT for FL-HCC. The
      5-year survival rate was greater in patients who underwent transplantation for FL
      HCC than for non-FL-HCC (39.4% and 11.2%, respectively). There was insufficient
      information available to determine the influence of tumor size, distribution,
      stage, and vascular invasion on survival, although most patients in whom tumor
      characteristics were specified had advanced disease. This study indicates that FL
      HCC carcinoma is a more favorable indication for OLT than non-FL-HCC in patients
      without underlying liver disease, although more detailed prognostic information
      is required to improve patient selection.

PMID- 10071347
TI  - Budd-Chiari syndrome associated with factor V leiden mutation: a report of 6
      patients.
AB  - Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction.
      Although myeloproliferative disorders are usually responsible for this severe
      thrombotic disorder, deficiency or dysfunction of the natural anticoagulants can
      be involved. Resistance to activated protein C caused by factor V Leiden mutation
      has been recently identified as a major cause of thrombophilia. We report 6
      patients with Budd-Chiari syndrome associated with factor V Leiden mutation
      combined with another acquired thrombophilic state (myeloproliferative disorder
      and lupus anticoagulant in 3 cases) and without another thrombophilic disorder in
      the other 3 cases. We conclude that factor V Leiden mutation should be evaluated
      in any case of hepatic vein occlusion because the prevalence of this mutation in
      the general population is high.

PMID- 10071348
TI  - Effect of t-tube clamping on the pharmacokinetics of mycophenolic acid in liver
      transplant patients on oral therapy of mycophenolate mofetil.
AB  - The aim of the study was to evaluate the effect of t-tube clamping on the
      pharmacokinetics of mycophenolic acid (MPA) after oral administration of
      mycophenolate mofetil (MMF) in primary liver transplant recipients treated with
      tacrolimus as the primary immunosuppressive drug. We evaluated the
      pharmacokinetics of MPA and its primary metabolite, mycophenolic acid glucuronide
      (MPAG), before and after clamping the t-tube in 8 primary liver transplant
      recipients treated with oral MMF and tacrolimus. The concentration of MPA and
      MPAG in plasma, bile, and urine samples obtained over one dosing interval was
      measured by high-pressure liquid chromatography. Pharmacokinetic parameters of
      MPA estimated before and after clamping the t-tube were compared to evaluate any
      significant differences at a P of.05 or less. There were no significant
      differences in the time to reach peak plasma concentration (1.8 +/- 1.7 v 1.0 +/-
      0.5 hours), trough plasma concentration of MPA (1.1 +/- 1.4 v 1.4 +/- 1.1
      microgram/mL), peak plasma concentration of MPA (10.6 +/- 7.5 v 11.1 +/- 4.6
      microgram/mL), area under the plasma concentration-versus-time curve (AUC) (40.1
      +/- 31.9 v 43.2 +/- 21.1 microgram/mL/h) of MPA, or the percentage of MPA that is
      free or unbound in the plasma (3.9% +/- 1.6% v 4.1% +/- 3.0%). There was also no
      significant difference in the ratio of the AUC of MPAG to MPA. These observations
      suggest that t-tube clamping does not affect the kinetics of MPA or MPAG and that
      no dosing alterations of MMF are required when the t-tube is clamped in liver
      transplant recipients.

PMID- 10071349
TI  - Comparison of pharmacokinetics of Neoral and Sandimmune in stable pediatric liver
      transplant recipients.
AB  - Cyclosporine (Sandimmune; Novartis Pharmaceuticals UK Ltd) is an effective
      immunosuppressive drug, but its lipid formulation and variable absorption may
      expose children to the risk of rejection during episodes of gastroenteritis after
      liver transplantation. Neoral (Novartis) is a microemulsified form of
      cyclosporine that may be better absorbed. In this study, the pharmacokinetic
      profiles of Neoral and Sandimmune were compared in stable children after liver
      transplantation to evaluate whether Neoral is more predictably absorbed. Eight
      children, 6 boys and 2 girls, with a mean age of 4.5 years (range, 1.2-12) were
      studied between 4 and 12 months after liver transplantation. Pharmacokinetic
      profiles were performed on each child by using the same dose (mg/kg) of Neoral or
      Sandimmune. Tmax, Cmax, Ctrough, and the area under the curve (AUC) were
      calculated and side effects were documented in children taking either drug for
      more than 3 months. Mean peak cyclosporine levels were higher and were achieved
      significantly sooner with Neoral (Cmax 790.5 +/- 216.5 ng/mL, P =.06; Tmax 1.8 +/
      1.0 hr, P =.01) than with Sandimmune (Cmax 589.4 +/- 313 ng/mL, Tmax 2.5 +/- 1.7
      hr), implying more rapid and better absorption. There was no significant
      difference in overall drug exposure (AUC) and 12-hour trough levels between the
      two formulations (P >.05). Children with Roux-en-Y loop biliary anastomosis
      taking Neoral, however, showed greater increases in AUC (mean increase = 37%)
      than those with duct-to-duct anastomosis (mean increase = 16%). There was no
      correlation between 12-hour trough level and AUC for either Neoral (r2 = 0.48) or
      Sandimmune (r2 = -0.08); however, for both drugs, AUC correlated very well with
      the 2-hour post-dose level (r2 = 0.68 and 0.7, respectively). Hirsutism was
      reported in 4 of 6 children on Neoral and may be associated with higher peak
      levels. Neoral is more consistently absorbed than Sandimmune in children after
      liver transplantation and may be more effective prophylaxis against rejection.
      Because of the increased peak levels and drug exposure, which may influence side
      effects, particularly in children with Sandimmune malabsorption, we recommend a
      1:0.75 dose conversion ratio in patients being converted from Sandimmune to
      Neoral.

PMID- 10071350
TI  - Improved cyclosporine bioavailability in black pediatric liver transplant
      recipients after administration of the microemulsion formulation.
AB  - Black transplant recipients are associated with low cyclosporine bioavailability,
      which may contribute to the poorer clinical outcomes observed with these
      patients. In this analysis, we compared cyclosporine exposure in black (n = 9)
      and nonblack (n = 18) pediatric maintenance liver transplant recipients by using
      steady-state pharmacokinetic profiles obtained after administration of the
      original and microemulsion formulations of cyclosporine. Treatment with the
      original cyclosporine formulation resulted in lower mean dose-normalized, area
      under the concentration-versus-time curve values for black compared with nonblack
      pediatric liver transplant recipients. On conversion to the microemulsion
      formulation of cyclosporine, black and nonblack patients experienced increases in
      cyclosporine bioavailability of 102% and 39%, respectively (P =.009 and P =.001).
      Because the increase in mean bioavailability was substantially greater for
      blacks, area under the concentration-versus-time curve values for this pediatric
      subpopulation became similar to those levels obtained for nonblacks receiving the
      microemulsion formulation for cyclosporine. When patients were further stratified
      by age, ethnic differences in bioavailability with the original formulation of
      cyclosporine were most apparent in the 1- to 5-year age group. Conversion to the
      microemulsion formulation resulted in a 164% increase (P =.05) in bioavailability
      for black patients within this age group such that, again, these levels became
      similar to area under the concentration-versus-time curve values obtained for
      young nonblacks receiving cyclosporine for microemulsion. Improvements in
      cyclosporine bioavailability after administration of the microemulsion
      formulation of cyclosporine may translate to improved long-term graft and patient
      outcomes for black pediatric liver transplant recipients.

PMID- 10071351
TI  - Cytochrome P-450 content and activity after cold storage of rat hepatocytes in
      university of wisconsin and sodium-lactobionate-sucrose solutions.
AB  - We compared the capacity of University of Wisconsin (UW) and of sodium
      lactobionate-sucrose (SLS) hypothermic preservation solutions to maintain the
      integrity of the hepatic cytochrome P-450-dependent mono-oxygenase system.
      Isolated rat hepatocytes were stored for 0, 10, 24, and 48 hours in UW or SLS
      solution and were subsequently cultured shortly at 37 degrees C. Cell viability
      declined slightly but significantly in a time-dependent manner during cold
      preservation in either UW or SLS solution, and warm culture exacerbated this
      effect. Total cytochrome P-450 declined gradually after cold preservation and
      warm culture to reach values of 70% and 52% of unstored controls in cells
      preserved for 24 and 48 hours in cold UW solution, respectively. Storage in cold
      SLS solution yielded a similar decrease to 79% and 59% of unstored controls for
      the equivalent preservation times. Cytochrome P-450 activity was assessed by the
      metabolism of theophylline after various cold preservation times in UW or SLS
      solutions. Production of the major metabolite 1,3-dimethyluric acid was not
      significantly affected by extended cold preservation periods in either UW or SLS
      solutions. Similarly, the amount of residual theophylline remained stable in all
      groups, suggesting that alternative metabolic routes were not modified. These
      studies show that cold preservation in SLS solution is as effective as that in UW
      solution in terms of cell viability, cytochrome P-450 content, and activity
      toward theophylline. In addition, the significant reduction in cytochrome P-450
      in conjunction with unaffected theophylline disposition suggests that certain
      cytochrome P-450 isoforms are specifically damaged by cold preservation and
      rewarming.

PMID- 10071352
TI  - Potential applications of N-terminal recombinant fragments of
      bactericidal/permeability-increasing protein in liver surgery.

PMID- 10071353
TI  - Mycophenolate mofetil, microemulsion cyclosporine, and prednisone as primary
      immunosuppression for pediatric liver transplant recipients.
AB  - Triple immunosuppressive therapy using mycophenolate mofetil (MMF), microemulsion
      cyclosporine (me-CsA), and prednisone offers the potential for potent
      immunosuppression without intravenous drug therapy or anti-T-cell antibody
      induction therapy. This report describes the application of an immunosuppressive
      protocol (CNp) using MMF, me-CsA, and prednisone as primary immunosuppression for
      pediatric liver transplant recipients at the University of California at San
      Francisco. From August 1995 through December 1996, 26 children (17 boys, 9 girls)
      aged 1 month to 16 years (mean +/- standard deviation, 58 +/- 62 months; median,
      31 months) underwent liver transplantation at our institution, receiving CNp as
      primary immunosuppression. Posttransplantation renal function, incidence of
      leukopenia, and drug tolerance within the group receiving CNp as primary
      immunosuppression were compared with those of 19 children who received primary
      immunosuppression consisting of azathioprine, oil-based gel-encapsulated
      cyclosporine, and prednisone with anti-T-cell antibody induction therapy at the
      same institution from October 1993 through July 1995. No significant difference
      was observed between immunosuppressive protocols in serum creatinine level or
      incidence of leukopenia requiring medical therapy during the first year
      posttransplantation. Whereas gastrointestinal symptoms were observed in
      approximately 30% of CNp recipients during initial immunotherapy, tolerance of
      CNp primary immunotherapy was routinely achieved by the dose reduction of MMF. At
      1 year posttransplantation, 20 children (77%) remained on CNp primary
      immunotherapy, 5 children (19%) were receiving tacrolimus-based immunotherapy
      secondary to rejection, and 1 patient (4%) converted to tacrolimus-based
      immunotherapy secondary to persistent gastrointestinal intolerance. In
      conclusion, CNp provides an alternative immunosuppressive protocol that
      eliminates the necessity of intravenous and induction immunosuppressive therapy
      with no increased incidence of posttransplantation renal dysfunction or
      leukopenia and is well tolerated in children.

PMID- 10071354
TI  - Primary adult liver transplantation under tacrolimus: more than 90 months actual
      follow-up survival and adverse events.
AB  - The introduction of tacrolimus has shown decreased rates of acute and steroid
      resistant rejection after liver transplantation (LTx). The aim of the present
      study is to examine the long-term efficacy and safety of tacrolimus in primary
      liver transplant recipients. The first 121 consecutive adults (aged >16 years)
      who underwent primary LTx at a single center from August 1989 to February 1990
      were followed up until August 1997. The mean follow-up was 93.2 +/- 1.2 months
      (range, 90.5 to 96.5 months). Patient survival, graft survival, rate of
      rejection, and adverse events were examined. The actual 7-year patient survival
      rate was 67.8%, and the graft survival rate was 63.6%. Infections, recurrence of
      disease, de novo malignancies, and cardiovascular events constituted the main
      causes of graft loss and death in the long term. Graft loss related to acute or
      chronic rejection was rare. The rate of acute rejection beyond 2 years was
      approximately 3% per year, and most rejections were steroid responsive.
      Approximately 70% of the patients received only tacrolimus after 1 year. Four
      patients developed end-stage renal disease, and 2 patients underwent kidney
      transplantation. Hyperkalemia and hypertension were observed in one third of the
      patients. New-onset insulin-dependent diabetes mellitus was observed in 9% and
      13% of the patients at the 1-year and 7-year follow-up, respectively. Seven
      patients developed de novo malignancies, including two skin malignancies. Six
      patients developed posttransplantation lymphoproliferative disorder during the
      entire follow-up period. Actual patient and graft survival at 7 years was
      excellent, and few adverse events developed after the first year. Graft loss from
      acute or chronic rejection was rare under tacrolimus, and approximately 70% of
      the patients were steroid free on tacrolimus monotherapy after the first year
      after LTx.

PMID- 10071355
TI  - Prolonged lactic acidosis after extended hepatectomy under in situ hypothermic
      perfusion.
AB  - A 46-year-old woman underwent right extended hepatectomy under total vascular
      occlusion with in situ hypothermic perfusion for colorectal metastasis.
      Immediately after surgery, she developed severe lactic acidosis, which required
      correction with sodium bicarbonate solution and ventilatory support for 36 hours.
      After 2 days, her lactate normalized, and the acidosis was corrected. She made an
      uneventful recovery. Persistent lactic acidosis after major hepatic resection
      under in situ hypothermic perfusion is a rare but reversible problem.

PMID- 10071356
TI  - Isolated tuberculosis of the pancreas after orthotopic liver transplantation.
AB  - A patient presented with intermittent high fever, upper abdominal pain, and loss
      of appetite 9 months after an orthotopic liver transplantation. Computed
      tomography showed a large mass in the pancreas that was confirmed at laparotomy.
      Pathological examination of the pancreatic biopsy specimen showed several chronic
      granulomatous lesions with caseating necrosis. Two and one half months after
      beginning antituberculous treatment, there was an important reduction of the
      pancreatic mass.

PMID- 10071357
TI  - Maximum sharing of cadaver liver grafts composite split and domino liver
      transplants.

PMID- 10071359
TI  - Atopic dermatitis: introduction and overview.

PMID- 10071360
TI  - Atopic dermatitis: the spectrum of disease.

PMID- 10071361
TI  - Treatment of atopic dermatitis.

PMID- 10071362
TI  - The role of food and inhaled allergens in atopic dermatitis.

PMID- 10071363
TI  - The role of infection in atopic dermatitis.
AB  - explain this tendency to develop infections. A decrease in the number and
      function of CD8+ suppressor/cytotoxic T cells from peripheral blood of AD
      patients has been reported.2 This could explain the increased incidence of
      cutaneous viral and fungal infections observed in these patients. Monocytes from
      AD patients secrete increased levels of interleukin (IL)-10 that can inhibit T
      cell mediated responses.3 Leukocytes from patients with AD have been found to
      produce decreased amounts of interferon gamma (IFN-g),4 which is required for the

PMID- 10071364
TI  - Emergency contraception in a travel context.

PMID- 10071365
TI  - Malaria chemoprophylaxis of 3,446 French travelers departing from Paris to eight
      tropical countries.
AB  - BACKGROUND: Each year more and more French travelers are visiting areas where
      malaria is endemic. The aim of this study was to assess prophylactic regimens
      used by French travelers and to determine whether they meet current published
      recommendations. METHODS: This 12 month transversal study (May 1, 1995 to April
      31, 1996) was conducted in embarkment lounges of Roissy Charles de Gaulle Airport
      to eight "tropical" destinations. RESULTS: 3,446 French travelers were enrolled.
      Twenty two and three-fifths percent of travelers had not sought any advice. The
      percentages of travelers staying less than 3 months (n = 2899) at risk of malaria
      (i.e., using none or inadequate chemoprophylaxis) were, according to the
      destination: Brazil (20%), Gabon (83%), Ivory Coast (26%), Kenya (43%),
      Madagascar (39%), Thailand (22%), Venezuela (41%) and Vietnam (8%). The
      suitability of the prophylaxis according to the information source for travelers
      staying less than 3 months varied as follows: specialist physician (OR = 1),
      travel agent (OR = 1.01, CI = 0.9 - 1. 1), occupational physician (OR = 1.13, CI
      = 0.6 - 2.1), GP (OR = 1. 58, CI = 1.1 - 2.3), none (OR = 1.95, CI = 1.3 - 2.9),
      friends (OR = 3, CI = 1.8 - 5) and pharmacist (OR = 3.94, CI = 2.1 - 7.5).
      Suitability of prophylaxis also varied according to the type of trip: organized
      tour (OR = 1), business trip (OR = 1.04, CI = 0.8 - 1.4), adventure tourism (OR =
      2.1, CI = 1.6 - 2.9) and visit to family or friends (OR = 2.3, CI = 1.7 - 3.1).
      CONCLUSIONS: This study shows that the quality of advice on antimalarial
      chemoprophylaxis varies markedly according to the source, and that nearly one in
      three French travelers (29.3 %, 850/2899) to tropical areas is at risk of
      malaria.

PMID- 10071366
TI  - Compliance of malaria chemoprophylaxis among travelers to India.
AB  - BACKGROUND: Compliance is an important issue in malaria chemoprophylaxis. The
      objective of the study was to determine reasons for noncompliance with
      chemoprophylaxis among international travelers to India. METHODS: A group of 452
      subjects traveling in the subcontinent were interviewed by directly administered
      questionnaire at two selected locations in Calcutta during October 1992. Full
      compliance was defined as the uninterrupted use of drugs, as per the World Health
      Organization (WHO) schedule, during travel up to the date of interview. RESULTS:
      Overall, the sample had a male preponderance (61%), with 155 (34%) being business
      travelers and 56% traveling for more than 3 weeks. Of the 158 (35%) reporting
      illness during travel, 5 persons tested positive for malaria. Compliance with
      chemoprophylaxis noted among 320 (71%) respondents in comparison to 21 (5%) found
      taking inadequate dosage or incorrect medication and 111 (24%) travelers being
      without any drugs. Backpackers and ethnic travelers as a group reported lower
      usage. Female, first visit and long-term travelers were less compliant.
      Inadequacy in pretravel advice, discontinuation due to side effects and active
      decision despite pretravel advice were common reasons for noncompliance. Past
      travel experience, concern for side effects, perceived uselessness and confusion
      arising from alternative regimens were also found to have influenced the decision
      making. CONCLUSION: We need to address the identified areas of conflict
      especially during pretravel counseling since improving compliance is our primary
      goal in malaria prevention among travelers today.

PMID- 10071367
TI  - Travel-related morbidity in travelers with insulin-dependent diabetes mellitus.
AB  - BACKGROUND: To assess whether there are clinically significant problems in
      patients with insulin-dependent diabetes mellitus (IDDM) traveling to tropical
      countries regarding metabolic dysregulations, infectious complications and
      general health problems. METHODS: A retrospective, descriptive cohort study by
      telephone interview of all IDDM patients who had received pretravel health advice
      at our travel clinic during a 12 month period. Data were collected on IDDM
      related problems: hypo-/hyperglycemic dysregulation, infectious complications,
      practical difficulties, exploring risk factors, as well as on general health
      problems. RESULTS: Of the 19 respondents, 13 (68%) reported any metabolic
      dysregulation, including all but one respondents with Type 1 diabetes. Fifty-five
      percent of Type 1 diabetics reported to have dysregulated more often than in the
      preceding period at home. Critical dysregulations occurred in 2 of the 19 study
      patients. Only 4 out of 11 (36%) type 1 IDDM patients increased frequency of
      blood glucose monitoring while traveling. Three travelers reported a febrile
      illness which resulted in hyperglycemic dysregulation. Five study patients
      experienced difficulties in the adjustment of their insulin dosage to the
      unfamiliar circumstances of traveling in the tropics. CONCLUSIONS: Metabolic
      dysregulation was a clinically significant problem, thus IDDM travelers to
      tropical destinations probably run extra health risks. Fever, easily acquired in
      the tropics, appeared to be an additional, serious health problem for this study
      population. As the number of diabetic travelers will increase, more research on
      the importance of risk factors possibly leading to dysregulation is necessary.

PMID- 10071368
TI  - Chronic fatigue syndrome among overseas development workers: A qualitative study.
AB  - BACKGROUND: A relatively high proportion of overseas development workers may
      develop chronic fatigue syndrome (CFS). A qualitative study was conducted in
      order to investigate how such people perceived their condition. METHODS: Twelve
      people who had developed CFS while working overseas with development
      organizations, or shortly after visiting development projects, were interviewed
      about their experiences. Their responses were analyzed using a grounded theory
      approach. RESULTS: Most of the participants considered themselves to have been
      extremely healthy before they developed CFS. The syndrome did not appear to have
      been caused by depression. The symptoms which were reported covered the range of
      symptoms typically found in studies of CFS. Respondents described difficulty in
      receiving, and accepting, a diagnosis. All of the participants attributed the CFS
      to multiple causes, the principal causes being overwork, stress and infections.
      Among the consequences of CFS reported to be the most difficult were having to
      leave the development project prematurely; pain; powerlessness; loss of
      independence, and the unpredictability of CFS. Factors which had helped
      respondents cope with these difficulties included religious beliefs; comparisons
      with people who were worse off than they were; thinking about positive
      consequences of the condition, and talking with supportive people. CONCLUSIONS:
      Some theories have suggested that CFS symptoms arise as a result of depression or
      other emotional difficulties, which the individual is not able to acknowledge.
      The results indicated that such theories may not apply to this subgroup of people
      with CFS. Further research on the etiology of CFS is warranted. Respondents
      described high levels of work-related stress as common to the experience of
      development work. It might be beneficial to train development workers in stress
      management techniques. Development organizations should be encouraged to ensure
      that their workers take sufficient time to rest, and attempts should be made to
      reduce work pressures.

PMID- 10071369
TI  - Emergency contraception in a travel context.

PMID- 10071370
TI  - Antiretroviral treatment and travel to developing countries.

PMID- 10071371
TI  - Diving and marine medicine review part I: diving physics and physiology.

PMID- 10071372
TI  - Sore eyes and travelers.

PMID- 10071373
TI  - Furuncular myiasis in a mother and child returning from Central America.

PMID- 10071374
TI  - Mixed malaria infection.

PMID- 10071375
TI  - Medical information on the internet 
AB  - Caveat lector et viewor - Let the reader and viewer beware! Thus sayeth Silberg
      et al.1 in their brief account of the apparent incompatibility between freedom of
      the press and accuracy of medical information. They point out that the problem is
      too much, rather than too little information. The Internet, where every Tom, Dick
      and Harry can be their own author, editor and publisher, is widely available to
      both lay and professional browsers. This has brought about a situation where a
      multitude of information seekers equipped with one or other search engine, wallow
      through a morass of material that ranges from first class research data to
      profound garbage. Without a medical background it is well-nigh impossible for the
      average person-in-the-street to sort the wheat from the chaff.

PMID- 10071376
TI  - Renewal of object relations through dream-work.
AB  - In this paper I describe my work with a suicidal patient. The patient was a woman
      who failed to realize her creative potential in a much wished for and
      unattainable profession of teacher and transferred all her energy and desire for
      leadership into her family life. The slogan of her life was the pathetic phrase:
      'Everything or nothing!' Her views on life differed from those of her husband
      who, at the age of 48, started a love affair with a 25-year-old woman. In
      relation to this, the patient became depressed and attempted suicide twice (by
      poisoning) in two years. From the Toxicology Department she was referred to the
      Psychiatric Department where she was treated as an out-patient.

PMID- 10071377
TI  - Dissociation and the self in the magical pre-Oedipal field.
AB  - This paper explores the clinical relevance of Jung's idea of the Self in pre
      Oedipal and pre-individuation psychology. Incorporating data from neurobiology
      and recent theories of memory and narrative reconstruction, a post-modern
      conception of the Self is proposed akin to what Jung called a 'dream of
      totality'. Such a conception of the Self is distinguished from a reified
      structure or a deified imago, and is considered to be that aspect of
      psychological functioning consonant with emerging meanings, and the birth of new
      psychological ground. Links are made back to Flournoy, William James, and depth
      psychology's early interest in teleology, the occult, and the creative capacities
      of the psyche. Updating this mystery tradition, clinical material illustrates how
      narratives of the Self are present in such pre-Oedipal dynamics as dissociation
      and projective identification. These dynamics are understood not only as
      primitive defences but as reconstitutive symbolic metaphors and mythopoetic
      expressions of an emergent rather than a superordinate Self.

PMID- 10071378
TI  - Rapid preconcentration method for the determination of pyrethroid insecticides in
      vegetable oils and butter fat and simultaneous determination by gas
      chromatography-electron capture detection and gas chromatography-mass
      spectrometry.
AB  - A simple and rapid solid-phase extraction (SPE)-GC method for the
      preconcentration and quantification of pyrethroids at low nanogram levels in oils
      and high fat content samples is presented. The method was studied using seven
      highly persistent pyrethroid insecticides, viz., cypermethrin, deltamethrin,
      fenvalerate, cyfluthrin, allethrin, cyhalothrin and permethrin. Preconcentration
      was achieved by treating the oil samples with methyltrioctylammonium chloride and
      subsequent elution of the pyrethroid molecules from a graphitized carbon black
      SPE cartridge using 5 ml of acetonitrile. Pyrethroid quantification was achieved
      by GC with electron capture detection. Recoveries of the pyrethroids at
      fortification levels of 0.05-0.5 ppm were 94-105%. Storage on graphitized carbon
      black for 30 d lowered the recovery of the pyrethroids by only 3-6%. The method
      compared well with results obtained by a GC-MS method. The relative standard
      deviation at a concentration level of 0.05-0.2 microgram ml-1 ranged from 1.31 to
      5.16%. The limit of detection achieved was 0.002 microgram ml-1 without any
      additional clean-up and with little interference from lipids during analysis.

PMID- 10071379
TI  - Monitoring the elimination of gadolinium-based pharmaceuticals. Cloud point
      preconcentration and spectrophotometric determination of Gd(III)-2-(3,5-dichloro
      2-pyridylazo)-5-dimethylaminophenol in urine.
AB  - An extraction methodology based on cloud point phase separation of non-ionic
      surfactants has been developed for the preconcentration of ppb amounts of
      gadolinium in urine as a prior step to its determination by an absorptiometric
      procedure. A method based on the formation of complexes with 2-(3,5-dichloro-2
      pyridylazo)-5-dimethylaminophenol was used for the extraction of Gd(III) in the
      surfactant-rich phase of non-ionic surfactant polyethyleneglycolmono-p
      nonylphenylether (PONPE 7.5). The variables affecting the combined
      preconcentration-absorptiometric method have been evaluated and optimised. The
      extraction efficiency, linearity, and the limit of detection (LOD) of the method
      were determined. The optimised procedure was applied to determine total and free
      Gd(III) contents in real urine samples of patients after the NMR imaging
      diagnostic examination with contrast agent.

PMID- 10071380
TI  - Detection of polar and macrocyclic trichothecene mycotoxins from indoor
      environments.
AB  - A method is described for the qualitative and semi-quantitative simultaneous
      determination of both non-macrocyclic and macrocyclic trichothecene biotoxins
      from samples derived from indoor environments. The method includes extraction,
      sample pre-treatment and reversed-phase HPLC separation followed by tandem mass
      spectrometric identification and quantification using electrospray ionization on
      a quadrupole ion trap mass analyser. Aqueous methanol was used in the initial
      extraction and solvent partitioning and solid-phase extraction in the
      purification of samples. The HPLC separation was run on-line with electrospray
      ionization MS-MS detection. The detection limits and recoveries of the procedure
      varied from 1 to 1000 pg and from 31 to 92%, respectively. As the method includes
      few and not very labour intensive sample treatment steps, it should allow for a
      high throughput of samples with good prospects of automation.

PMID- 10071381
TI  - Near-infrared spectroscopy in the pharmaceutical industry.

PMID- 10071382
TI  - AGANTG: a Microsoft EXCEL 5.0-visual basic routine for the analysis of dose
      response data.
AB  - A Microsoft EXCEL 5.0 program was developed to evaluate data from biochemical and
      functional bioassays, an important step in drug discovery. The program
      accommodates both agonist and antagonist data. The program, written entirely in
      Visual Basic, is compatible with both Macintosh and PC platforms. Data are
      conveniently entered into a worksheet following only a few simple rules. The
      program performs complex data analysis and outputs calculated and graphic results
      to EXCEL worksheets. A set-up routine with a convenient dialog box offers the
      user controls regarding data analysis and results formats. After determining if
      the data are from an agonist or antagonist assay, the program automatically
      performs the analysis and outputs results in the proper format. Calculations
      support Schild analysis for antagonists. An agonist and antagonist were analyzed
      to illustrate program usage and results generated by the analysis. EXCEL-Visual
      Basic is a useful and convenient tool for evaluating bioassay data. Data entry is
      greatly simplified and custom reports can be generated with relative ease. Data
      are stored in a format that allows for easy editing re-analysis.

PMID- 10071383
TI  - Solid-phase reactors as high stability reagent sources in flow analysis:
      selective flow injection spectrophotometric determination of cysteine in
      pharmaceutical formulations.
AB  - The flow injection spectrophotometric determination of cysteine was carried out
      by reaction with cobalt(II) ions entrapped in a polymeric material and filling a
      packed-bed reactor; the released cobalt(II) complexed with the amino acid was
      monitored at 360 nm. The method worked with a high repeatability, even with
      independent reactors, days and solutions. Selectivity of the procedure was tested
      with twenty different foreign compounds found in pharmaceutical formulations
      containing cysteine, parent amino acids included; no serious interferences were
      observed. The calibration graph for cysteine was linear over the range 1-90
      micrograms ml-1 with a relative standard deviation of 0.8% at 60 micrograms ml-1
      (n = 158). The calculated sample throughput was 90 h-1. The method was applied to
      determine the content of cysteine in pharmaceutical formulations.

PMID- 10071384
TI  - Speciation determination of arsenic in urine by high-performance liquid
      chromatography-hydride generation atomic absorption spectrometry with on-line
      ultraviolet photooxidation.
AB  - A coupled system for arsenic speciation determination based on high-performance
      liquid chromatography (HPLC), on-line UV photooxidation and continuous-flow
      hydride generation atomic absorption spectrometry (HGAAS) was built from
      commercially available modules with minor modifications to the electronic
      interface, the software and the gas-liquid separator. The best results were
      obtained with strong anion-exchange columns, Hamilton PRP X-100 and Supelcosil
      SAX 1, and gradient elution with phosphate buffers containing KH2PO4-K2HPO4. The
      on-line UV photooxidation with alkaline peroxodisulfate, 4% m/v K2S2O8-1 mol l-1
      NaOH, in a PTFE knotted reactor for 93 s ensures the transformation of inorganic
      AsIII, monomethylarsonate, dimethylarsinate, arsenobetaine, arsenocholine,
      trimethylarsine oxide and tetramethylarsonium ion to arsenate. About 32-36 HPLC
      UV-HGAAS runs could be performed within 8 h, with limits of detection between 2
      and 6 micrograms l-1 As, depending on the species. The method was applied to the
      analysis of spot urine samples and certified urine reference materials (CRMs).
      Upon storage at 4 degrees C, reconstituted CRMs are stable for at least 2 weeks
      with respect to both their total arsenic content and the individual species
      distribution.

PMID- 10071385
TI  - Validated determination of total arsenic species of toxicological interest
      (arsenite, arsenate and their metabolites) by atomic absorption spectrometry
      after separation from dietary arsenic by liquid extraction: toxicological
      applications.
AB  - A validated method for the selective extraction of total As species of
      toxicological interest (arsenite, arsenate and mono- and dimethylated arsenic
      species) from urine, followed by atomic absorption spectrometric determination,
      is described. The mechanisms involved in extraction were studied and the
      extraction method was optimized. The urine sample was acidified with concentrated
      HCl and KI and sodium hypophosphite were added. Under these conditions, As
      species were reduced to their corresponding iodide arsines, extracted with
      toluene and back-extracted with 1 mmol l-1 NaOH solution. Only inorganic arsenic
      and its metabolites in humans (monomethylarsonic and dimethylarsinic acid) were
      extracted. Arsenobetaine of dietary origin was not extracted. This method can
      detect if any As increase in urine originates from inorganic As intoxication or
      only from dietary non-toxic As species such as arsenobetaine.

PMID- 10071386
TI  - Determination of bismuth in urine and prescription medicines using atomic
      absorption with an on-line hydride generation system.
AB  - The bismuth contents of various digested urine samples and prescription medicines
      were determined by atomic absorption spectrometry combined with hydride
      generation. The procedure followed was a standard addition method for urine and
      direct calibration for the prescription medicines. The detection limit of the
      method was determined to be 320 pg ml-1 Bi with an analytical frequency of 150 h
      1. A relative standard deviation of 4.7% was found for Bi in urine at the level
      of 4.3 ng ml-1 Bi. Interference caused by NiII, CoII, CuII, AgI, SeIV, SbIII and
      HgII could be controlled with a masking solution of thiourea (0.2%)-KI (10%).

PMID- 10071387
TI  - In vitro mineral availability from digested tea: a rich dietary source of
      managanese.
AB  - Tea is potentially a rich source of some dietary metals and approximately 70 l
      are drunk per capita per year in the UK. In particular, tea may be an important
      source of Mn, since leaf tea contains 350-900 micrograms g-1 of this essential
      element. However, the leaching and bioavailability of Mn from tea have been
      little studied, so a recently developed in vitro assay was applied to compare the
      bioavailability of Mn from tea infusions with that of other major and trace
      essential elements. Analysis of tea infusions before digestion showed that 1.0 l
      contained 115% of the average daily dietary intake of Mn but < 6% of all other
      minerals. Samples of these infusions were incubated with human gastric juice (37
      degrees C, 1 h) and some were then adjusted to pH 6.5 to simulate intestinal pH.
      All were centrifuged through ultrafilters with molecular mass cut-offs of 3, 10
      and 30 kDa. The percentages of ultrafilterable (< 3 kDa) elements following
      simulated gastrointestinal digestion were (n = 3; mean +/- s) Ca 47.7 +/- 10.7,
      Cu 45.3 (n = 1), Fe < 5, Mg 66.4 +/- 1.6, Mn 39.8 +/- 11.4, K 40.3 +/- 2.2, Na
      100.0 +/- 5.3 and Zn 33.7 +/- 1.1. Hence the ultrafilterability of elements
      showed the general trend M+ > M2+ > M3+, which is probably the inverse of the
      order of their strengths of binding to tea polyphenols. However, Mn was the only
      element found in significant dietary amounts in tea, and under simulated
      intestinal conditions was still 40% bioavailable.

PMID- 10071388
TI  - Simultaneous determination of piroxicam and its major metabolite 5'
      hydroxypiroxicam in human plasma by derivative spectrophotometry.
AB  - A first-derivative spectrophotometric method for the simultaneous determination
      of piroxicam (PX) and its major metabolite 5'-hydroxypiroxicam (OH PX) in human
      plasma is described. The method consists of direct extraction of the two drugs
      from the plasma samples with hydrochloric and trichloroacetic acid prior to their
      determination by measuring the first-derivative signals at 337.0 nm for PX and at
      327.0 nm for OHPX (zero-crossing wavelength). The calibration graphs were linear
      up to 10.0 and 8.0 mg l-1 of PX and OH PX, respectively, and the limits of
      quantification were 0.27 and 0.56 mg l-1. The possible interfering effects of
      other substances were studied.

PMID- 10071389
TI  - Electron spin resonance detection of radiosterilization of pharmaceuticals:
      application to four nitrofurans.
AB  - The detection and dosimetry of radiosterilization of pharmaceuticals is a growing
      concern to numerous government regulatory agencies worldwide. In the absence of
      suitable detection methods, attention was focused on electron spin resonance
      (ESR) spectrometry. This paper reports experimental data on ESR dosimetry of
      irradiated nitrofurans (nitrofurantoin, nifuroxazide, nifurzide and nifurtoinol).
      Whereas the ESR spectrum of a non-irradiated sample shows no signal, a signal,
      that is dependent on the irradiation dose is observed with irradiated samples.
      The number of free radicals was calculated by comparing the second integral from
      radiosterilized samples and a Bruker strong pitch reference; the values were in
      the range 1.1 x 10(18)-1.5 x 10(19) radicals mol-1 (G = 0.003-0.03). In addition
      to qualitative detection, ESR spectrometry can be used for dose determination.
      When a bi-exponential function is applied to the variation of the peak-to-peak
      amplitude versus dose, the function correlates well with the data. However, an
      exponential function, easier to use than a bi-exponential function, will probably
      be sufficient for dose determination by retrospective dosimetry. Decay of
      radicals upon storage was modelled using a bi-exponential function. From this,
      the time limit from the irradiation (25 kGy) for identification of irradiated
      nitrofurans by ESR can be evaluated. With regard to the commercial aspects of
      drugs, radicals should be detected up to 2 years after irradiation. The kinetic
      decrease makes discrimination between irradiated and non-irradiated nitrofurans
      possible even after storage for up to 2 years, except for nifurtoinol.

PMID- 10071390
TI  - Determination of tromethamine in an eye-care pharmaceutical by capillary
      electrophoresis.
AB  - Tromethamine [tris(hydroxymethyl)aminomethane] is used as an emulsifying agent,
      alkaliser and buffering agent in pharmaceutical preparations such as eye-care
      solutions. A new method for the determination of this compound in an eye-care
      preparation was developed using capillary zone electrophoresis with indirect UV
      detection. The method displayed linearity between 2.5 and 25 mg l-1 with a
      correlation coefficient of 0.9992. The limit of detection was 2.5 mg l-1.
      Precision and accuracy were determined as relative standard deviation and %
      deviation, and were found to be 0.42% and 1.62%, respectively. Recovery studies
      of tromethamine in the pharmaceutical preparation gave a 102.98% recovery.

PMID- 10071391
TI  - Direct injection determination of theophylline and caffeine in blood serum by
      high-performance liquid chromatography using an ODS column coated with a
      zwitterionic bile acid derivative.
AB  - An ODS column dynamically coated with zwitterionic bile acid derivative, 3-[(3
      cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), was evaluated for
      direct injection determination of drugs in blood serum by HPLC. Polar functional
      groups such as sulfonate, ammonium and the three hydroxyl groups in CHAPS
      protruding towards an aqueous mobile phase formed a hydrophilic layer over the
      ODS reversed-phase surface, which resulted in high molecular mass compounds such
      as proteins being prevented from penetrating into the internal hydrophobic
      region. The bulk of the proteins were eluted as an unretained or nearly
      unretained band by using 0.2 mM sodium hydrogenphosphate solution (pH 7.4) as the
      mobile phase. In contrast, small molecules such as some inorganic anions and
      aromatic compounds were retained and thereby separated from one another. It was
      confirmed that the ODS column modified with CHAPS acts as a restricted access
      type column with a hydrophobic interior and a hydrophilic exterior. Hence
      biological fluids could be directly injected into the CHAPS-coated ODS column.
      The present HPLC system using the CHAPS-coated ODS column was applied to the
      determination of theophylline and caffeine in human blood serum. The detection
      limits for the two drugs with UV absorption at 273 nm were 0.2 and 0.5 mg l-1
      (injection volume 20 microliters) and the relative standard deviations of peak
      area measurements were < 1.4% and 2.2%, respectively, for 10 replicate
      measurements of serum spiked with 5 mg l-1 of each of the drugs.

PMID- 10071392
TI  - Highly sensitive flow detection of uric acid based on an intermediate
      regeneration of uricase.
AB  - The principle of the signal amplification of a uric acid sensor based on
      dithiothreitol (DTT)-mediated intermediate regeneration of uricase was applied to
      a flow-injection system with an immobilized uricase reactor and a DTT-containing
      carrier. Highly sensitive detection for nM to microM order of uric acid was
      achieved when 10 mM TRIS-HCl buffer (pH 10.0) containing 20 mM DTT was used as a
      carrier at 0.6 ml min-1 and 37 degrees C. The sensitivity of the uric acid was
      much improved over a batch method using a uricase membrane-coupling electrode,
      and the detection limit (ca. peak current 8 nA) of uric acid was found to be down
      to 3 x 10(-10) M (amplification factor; more than 10,000). This chemically
      amplified flow-system is very useful for the direct assay of uric acid in highly
      diluted biological fluids (urine and serum) without complicated pretreatment of
      the samples, because this sensor has the potential to detect trace amounts (nM to
      microM) of uric acid in highly diluted body fluids in which the concentration of
      interfering constituents was decreased to negligible levels. Good correlation was
      observed between this system and conventional spectrophotometry. The immobilized
      uricase reactor could be re-used for at least 4 months of repeated analysis
      without loss of activity and was stable if stored at 4 degrees C in 10 mM TRIS
      HCl buffer, pH 9.0.

PMID- 10071393
TI  - Oral contraception and health.

PMID- 10071394
TI  - Evaluating primary care groups.

PMID- 10071395
TI  - Ten year follow-up of depression after diagnosis in general practice.
AB  - BACKGROUND: Depression is a serious illness with a high recurrence rate,
      mortality, and suicide rate, and a substantial loss of quality of life. Long-term
      course of depression, in particular of patients not referred to specialist care,
      is not completely clear. We performed a study in which the course of depression
      in general practice was studied for 10 years after the first diagnosis. AIM: To
      learn more about long-term course and outcome of patients with depressive illness
      for a full 10 years after diagnosis. METHOD: A historic cohort study with 386
      patients classified as depressive before January 1984, recruited from four
      general practices belonging to the Continuous Morbidity Registry of the
      University of Nijmegen in The Netherlands. This cohort was followed up for 10
      years. Mortality was compared with a control group matched for age, sex, social
      class, and practice. Of 222 patients out of this cohort who could be followed up
      for a full 10 years after diagnosis, the case records were studied in detail.
      RESULTS: No statistically significant difference was found in mortality between
      the 386 patients and the control group. Recurrence of depressive episodes did not
      occur in about 60% of the 222 patients (confidence interval 54% to 67%). Of the
      depressive patients, 15% were referred to secondary care and 9% were admitted to
      hospital. CONCLUSION: Mortality, suicide, and recurrence rate were lower than
      expected, taking into account what is known from depression studies in
      psychiatry. These results stress the importance of long-term prospective follow
      up studies of all patients with depression because of the emphasis on case
      finding and treatment without exact knowledge of long-term course and outcome of
      patients who were not referred.

PMID- 10071396
TI  - Individual and organizational predictors of depression in general practitioners.
AB  - BACKGROUND: High levels of stress and depression are seen in both general
      practitioners (GPs) and hospital doctors, and this has implications for patient
      care. It is therefore important to discover the individual and organizational
      causes of elevated symptoms so they can be tackled. AIM: To discover the relative
      importance of individual characteristics measured 10 years earlier compared with
      current organizational stressors in predicting depression in GPs. METHOD:
      Longitudinal questionnaire study, using data from those of the original cohort of
      318 medical students who are now GPs (n = 131), considering perceptions of
      current stressors and comparing through regression analyses the relative strength
      of early personality and mood with current organizational factors of sleep, hours
      worked, and practice size in predicting current depression levels. RESULTS: There
      were 22 (17%) stressors scoring above threshold for depression. Relationships
      with senior doctors and patients are the main reported stressors, followed by
      making mistakes and conflict of career with personal life. The predictors of
      symptom levels varied for men and women. In men, depression and self-criticism as
      students, and current sleep levels; and in women, sibling rivalry and current
      alcohol use, were the main predictors: in men, 27% of the variance was accounted
      for by early dispositional factors alone compared with 14% in women. A model is
      suggested linking sleep loss with workplace stressors, self-critical cognitions,
      and depression. CONCLUSION: Interventions can be made throughout training,
      targeting self-criticism and recognizing early depression, while later addressing
      the organizational stressors, particularly work relationships and sleep patterns.

PMID- 10071397
TI  - The impact of depression on the physical health of family members.
AB  - BACKGROUND: Depressive illness is common. Depression in one family member is
      associated with an increased incidence of psychopathology in other family
      members. There are no data on the physical well being of the families of
      depressed individuals. AIM: To compare physical morbidity of family members of
      depressed patients with that of family members of comparison patients. METHOD: A
      comparative follow-up study from case notes. Two hundred and one subjects from 88
      families with an index family member diagnosed with depression ('depression
      families') were compared with 200 subjects from 88 families with a matched index
      subject without depression ('comparison families'), using the Duke University
      Illness Severity Scores (ISS) to assess burden of illness experienced by both
      groups. RESULTS: The cumulative incidence of depression over 11 months in
      depression families was 8.9% compared to 1.4% in the Family Practice Unit as a
      whole. Members of depression families had significantly greater ISS than members
      of comparison families (difference in means = 0.164; 95% confidence interval (CI)
      0.113-0.215; P < 0.001). Excluding family members with depression (in addition to
      the index subject), ISS of members of depression families remained significantly
      greater than the comparison group (difference in means = 0.136; 95% CI 0.083
      0.189; P < 0.001). Among depression families, mean ISS was significantly higher
      after presentation of depression in index subjects compared with before
      (difference in means = 0.155; 95% CI 0.115-0.194; P < 0.0001). No significant
      difference was seen between ISS of depression and comparison families before
      presentation of depression (difference in means = 0.008; 95% CI -0.004-0.058; P =
      0.74). CONCLUSION: Depression in patients is associated with increased physical
      morbidity in their families.

PMID- 10071398
TI  - The risk of serious illness among oral contraceptive users: evidence from the
      RCGP's oral contraceptive study.
AB  - BACKGROUND: So far, no-one has attempted to evaluate the overall balance of
      serious, but not necessarily fatal, disease among a cohort of oral contraceptive
      users. AIM: To emprirically assess the balance of risk of serious illness among a
      cohort of oral contraceptive users followed up for up to 28 years. METHODS: Oral
      contraceptive-associated serious disease was defined as that which is often life
      threatening and/or associated with long-term disability, and which has been
      found, or postulated, to be associated with use of combined oral contraceptives.
      Data from the Royal College of General Practitioners' (RCGP) Oral Contraception
      Study were examined to determine the rate of such conditions during 335,181 woman
      years of observation in 'ever users' and 228,727 woman-years in 'never users'.
      The rates were standardized for age, parity, social class, and smoking. RESULTS:
      Compared with never users, ever users had a small increased risk of any serious
      disease (relative risk = 1.17; 95% confidence interval = 1.09-1.25). Ever users
      had an excess risk of cerebrovascular disease, pulmonary embolism, and venous
      thromboembolism, and reduced risk of ovarian and endometrial cancer. The
      increased risk was seen only in younger women; by the age of 50, ever users had
      the same risk as never users. The risk appeared to be confined to women using
      older oral contraceptives containing 50 micrograms or more of oestrogen.
      CONCLUSIONS: Past users of older, higher dose oral contraceptives can be
      reassured that the small increased risk of serious disease seen during current
      use does not persist after stopping, and that latent effects do not appear later
      in life. Currently available oral contraceptives, containing less than 50
      micrograms of oestrogen accompanied by the progestogen, levonorgestrel, or
      norethisterone acetate, do not appear to be associated with an increased net risk
      of serious disease.

PMID- 10071399
TI  - Stress and morale in general practice: a comparison of two health care systems.
AB  - BACKGROUND: Poor morale and high levels of stress among general practitioners
      (GPs) are causing concern. Little research has previously been carried out to
      study possible differences in morale and stress between GPs working in two
      different but geographically similar health care systems. AIM: To compare
      perceived levels of stress and morale between GPs working in two different health
      care systems--one having a state monopoly (Northern Ireland) and the other having
      mixed private and state funding (Republic of Ireland)--and to look for factors
      that might help explain any differences in stress levels and morale between the
      two systems. METHOD: Anonymous and confidential questionnaires were sent to all
      986 National Health Service (NHS) GPs in Northern Ireland (NI) and a random
      sample of 900 GPs in the Republic of Ireland (ROI). A common set of core
      questions on demographic details, partners and work patterns, perceived levels of
      stress and morale, safety, violence, and complaints were asked. RESULTS: Response
      rates were high in both areas: 91% in NI and 78% in the ROI. GPs in NI had
      significantly higher stress levels and significantly lower levels of morale than
      GPs in the ROI. The NI sample expect matters to get worse over the following
      year. Doctors in the ROI were more likely to be single handed and to work from
      two sites. Also, more GPs in ROI had fears for their safety and had been the
      subject of physical violence, but fewer had received complaints and medico-legal
      actions than in NI. CONCLUSIONS: A significant proportion of both groups of
      doctors report feeling highly stressed but GPs in NI appear more unhappy and have
      a poorer outlook for the future. It is suggested that the structure, management,
      and expectations of the NHS have taken a severe toll on its GPs, whereas a system
      in which doctors have less practice support but more control is good for morale.

PMID- 10071400
TI  - Patient removals from general practitioner lists in Northern Ireland: 1987-1996.
AB  - BACKGROUND: Being struck off a general practitioner's list is a major event for
      patients and a subject for much media attention. However, it has not hitherto
      received much research attention. AIMS: To quantify the numbers of patients
      removed at doctors' request in Northern Ireland between 1987 and 1996. To
      describe the characteristics of those removed and to determine if the rate of
      removal has increased. METHODS: This is a descriptive epidemiological study
      involving a secondary data analysis of records held by the Central Services
      Agency. RESULTS: Six thousand five hundred and seventy-eight new patients were
      removed at general practitioner (GP) request between 1987 and 1996. This equated
      to 3920 removal decisions, a rate of 2.43 per 10,000 person-years. The very young
      and young adults had the highest rates of removal; most of the young being
      removed as part of a family. Ten point six per cent of removed patients had a
      repeat removal, and 16.3% of first removal decisions required an assignment to
      another practice. Family removals have decreased and individual removals have
      increased over the 10 years. Disadvantaged and densely populated areas with high
      population turnover were associated with higher rates of removal, though
      heterogeneity is evident between general practitioners serving similar areas.
      Compared to the period 1987 to 1991, removal rates for the years 1992 to 1993
      were reduced by 20.0% (95% confidence interval (CI) for rate ratio (RR) 0.73
      0.87), and those for the years 1994 to 1996 increased by 8% (95% CI = 1.01-1.16).
      The greatest increase was in the over-75 years age group (standardized RR = 1.60;
      95% CI = 1.57-1.62). CONCLUSIONS: Removals are relatively rare events for both
      patients and practices, though they have been increasing in recent years. Further
      research is needed to understand the processes that culminate in a removal.

PMID- 10071401
TI  - The relationship between census-derived socio-economic variables and general
      practice consultation rates in three town centre practices.
AB  - BACKGROUND: The relationship between socio-economic factors and consultation
      rates is important in determining resource allocation to general practices. AIM:
      To determine the relationship between general practice surgery consultation rates
      and census-derived socio-economic variables for patients receiving the same
      primary and secondary care. METHOD: A retrospective analysis was taken of
      computerized records in three general practices in Mansfield, North
      Nottinghamshire, with 29,142 patients spread over 15 electoral wards (Jarman
      score range from -23 to +25.5). Linear regression analysis of surgery
      consultation rates at ward and enumeration district levels was performed against
      Jarman and Townsend deprivation scores and census socio-economic variables.
      RESULTS: Both the Townsend score (r2 = 59%) and the Jarman score (r2 = 39%) were
      associated with surgery consultation rates at ward level. The Townsend score had
      a stronger association than the Jarman score because all four of its component
      variables were individually associated with increased consultations compared with
      four out of eight Jarman components. CONCLUSIONS: Even in practices not eligible
      for deprivation payments there were appreciable differences in consultation rates
      between areas with different socio-economic characteristics. The results suggest
      that the variables used to determine deprivation payments should be reconsidered,
      and they support suggestions that payments should be introduced at a lower level
      of deprivation and administered on an enumeration district basis.

PMID- 10071402
TI  - A decade of caring for drug users entirely within general practice.
AB  - BACKGROUND: The government encourages general practitioners (GPs) to become
      involved in caring for drug users. However, in some areas of the country,
      including Bedford, secondary care support is inadequate. GPs in these areas have
      to decide how to cope with such patients entirely within general practice. AIM:
      To assess the characteristics and quality of care given without secondary care
      support to drug users by one practice in Bedford over a decade. METHOD: A search
      was made of the practice computer for all patients with a problem title of
      'addiction drug' between 1986 and 1995. The age, sex, social characteristics, and
      drug history were recorded. RESULTS: One hundred and ninety-two patients were
      found, of which 155 took part in the practice programme; i.e. they consulted more
      than three times. Forty-three patients (37%) who took part and were prescribed
      Methadone were prescribed this drug as ampoules. Sixty-three patients (40.6%) who
      took part in the programme stopped using drugs. Thirty-two (33.6%) of the
      Methadone users became abstinent. A higher proportion of women (13-48%) than men
      (19-27.7%) stopped using Methadone (P = 0.019). Among patients who had a stable
      lifestyle, a higher proportion had been prescribed ampoules than mixture (22 out
      of 28: 78.6%; P = 0.001). Similarly, of those who had a job, eight out of 11
      (72%; P = 0.037) had been prescribed methadone ampoules. Two-thirds of all
      patients prescribed amphetamines stopped using drugs. CONCLUSION: Long-term care
      of drug users entirely within general practice is feasible. Among those
      prescribed methadone ampoules, a higher than average proportion had stable
      lifestyles and had a stable job.

PMID- 10071403
TI  - Development of a thyroid function strategy for general practice.
AB  - A study was carried out to investigate a thyroid stimulating hormone (TSH)
      frontline strategy that could potentially result in a more straightforward
      interpretation of thyroid function tests, a reduction in the number of
      inappropriate referrals to medical outpatients, an improvement in the 'turnaround
      time' of results, and a reduction in the number of unnecessary tests carried out,
      thereby reducing costs.

PMID- 10071404
TI  - Teenage mothers and their peers: a research challenge.
AB  - Recent reports have highlighted the adverse health experience of teenage mothers.
      The question of how these mothers' perceptions of their own health status and
      social networks differ from those of their nulliparous peers is explored in this
      pilot study, which highlights some practical problems associated with research in
      this important field.

PMID- 10071405
TI  - General practitioners' knowledge and experience of the abuse of older people in
      the community: report of an exploratory research study in the inner-London
      borough of Tower Hamlets.
AB  - A pioneering study aimed to quantify general practitioners' (GPs') knowledge of
      cases of elder abuse in the community. The research found that elder abuse is a
      problem encountered by GPs, and that a large majority of responders would welcome
      training in the identification and management of the problem.

PMID- 10071406
TI  - General practitioners' continuing education: a review of policies, strategies and
      effectiveness, and their implications for the future.
AB  - BACKGROUND: The accreditation and provision of continuing education for general
      practitioners (GPs) is set to change with new proposals from the General Medical
      Council, the Government, and the Chief Medical Officer. AIM: To review the
      theories, policies, strategies, and effectiveness in GP continuing education in
      the past 10 years. METHOD: A systematic review of the literature by computerized
      and manual searches of relevant journals and books. RESULTS: Educational theory
      suggests that continuing education (CE) should be work-based and use the
      learner's experiences. Audit can play an important role in determining
      performance and needs assessment, but at present is largely a separate activity.
      Educational and professional support, such as through mentors or co-tutors, has
      been successfully piloted but awaits larger scale evaluation. Most accredited
      educational events are still the postgraduate centre lecture, and GP Tutors have
      a variable role in CE management and provision. Controlled trials of CE
      strategies suggest effectiveness is enhanced by personal feedback and work
      prompts. Qualitative studies have demonstrated that education plays only a small
      part in influencing doctors' behavior. CONCLUSION: Maintaining good clinical
      practice is on many stakeholders' agendas. A variety of methods may be effective
      in CE, and larger scale trials or evaluations are needed.

PMID- 10071407
TI  - General practice and the new science emerging from the theories of 'chaos' and
      complexity.
AB  - This paper outlines the general practice world view and introduces the main
      features of the theories of 'chaos' and complexity. From this, analogies are
      drawn between general practice and the theories, which suggest a different way of
      understanding general practice and point to future developments in general
      practice research. A conceptual and practical link between qualitative and
      quantitative methods of research is suggested. Methods of combining data about
      social context with data about individuals and about biomedical factors are
      discussed. The paper emphasizes the importance of data collected over time and of
      considering the multiplicative interactions between variables. Finally, the paper
      suggests that to develop this type of research, general practice many need to
      reassess systems of categorizing and recording appropriate data.

PMID- 10071408
TI  - Counselling in primary care.

PMID- 10071409
TI  - Sickness certification.

PMID- 10071410
TI  - Simulated surgery.

PMID- 10071411
TI  - Deprivation payments and workload.

PMID- 10071412
TI  - GP out of hours service.

PMID- 10071413
TI  - Private health screening.

PMID- 10071414
TI  - Screening for cervical cancer.

PMID- 10071415
TI  - Recruitment of general practitioners to a randomized trial.

PMID- 10071416
TI  - Consilience in medicine.

PMID- 10071417
TI  - Ethanol, GABA and epilepsy.
AB  - Ethanol exerts its behavioral effects largely by interacting with receptors to
      brain neurotransmitters. The molecular mechanisms involving these interactions
      are still not well known since an ideal model for their study is currently
      unavailable. In addition, responses to alcohol may vary due to factors such as
      genetic predisposition, ethanol concentration consumed, and stimuli such as
      stress, socialization, etc. The chronic consumption of alcohol, similar to that
      of other drugs such as benzodiazepines and barbiturates, is linked to GABAergic
      neurotransmission. GABA is the predominant inhibitory neurotransmitter in the
      brain. In a context of substance abuse, these three drugs first cause a
      gratifying effect, later tolerance and finally, physical and psychological
      dependence. If consumption is interrupted abruptly, a withdrawal syndrome occurs.
      The Alcohol Withdrawal Syndrome (AWS) is a state of hyperexcitability
      characterized by anxiety, fear, muscular rigidity and tonic-clonic seizures with
      epileptiform-type characteristics. The epileptic seizures seen during AWS are
      often similar to those seen in experimental epilepsy models such as "kindling" or
      GABA Withdrawal Syndrome (GWS) models. A possible correlation between these
      models and AWS will allow for a better understanding of the cellular and
      molecular effects that alcohol exerts on the brain.

PMID- 10071418
TI  - Changes in cathepsin D activity of maternal tissues during lactation and weaning
      in rats.
AB  - BACKGROUND: A loss of proteins from maternal tissues during lactation has been
      demonstrated. Protein loss could be explained by intracellular proteolysis.
      METHODS: Cathepsin D activity was studied in the liver, muscle and mammary gland
      of lactating and weaned rat dams. Lactation was studied at maximal milk
      production (L-14) and at the final stage of lactation (L-21). RESULTS: Basal
      activity (virgin rats) was three times higher in liver and mammary gland than in
      muscle. At both stages, L-14 and L-21, cathepsin D activity increased in liver
      (50%) as well as in the gland (164%), but no change was observed in muscle, when
      compared with controls. Twenty-four hours after litter separation, enzyme
      activity in the liver decreased to basal levels, while in the mammary gland
      cathepsin D activity showed a significant decrease but remained higher than
      control levels. CONCLUSION: Our results show that liver exhibits adaptive changes
      in the catabolism of proteins in response to the increased demands imposed by
      lactation on the maternal organism, and when the stimuli disappear activity
      returns to basal levels. The high activity in mammary gland indicates fast
      turnover of structures and biomolecules as an answer to the high synthetic
      activity in this tissue. Activity remained higher in the weaning rats, as a
      result of the regression process which the mammary gland is undergoing.

PMID- 10071419
TI  - Changes in antioxidant enzyme activities and lipid peroxidation related to
      bromoethylamine-induced renal cytotoxicity.
AB  - BACKGROUND: The effect of bromoethylamine (BEA) administration on lipid
      peroxidation and on the activities of antioxidant enzymes was studied. METHODS:
      Adult rats received BEA at 1.2 mmol/kg, a dose that produces renal papillary
      necrosis. Lipid peroxidation assessed by maximal rate in MDA formation, the
      activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px), and the levels of non-protein sulfhydryls (NPSH) were measured in renal
      cortex and papilla of control and BEA-treated animals. RESULTS: After BEA
      treatment, an increment in lipid peroxidation in papilla and cortex was found
      after 1.5 and 24 hours of treatment. Catalase activity decreased in both regions,
      but earlier in cortex. CONCLUSION: These data suggest some role of oxidative
      stress in the mechanism of BEA-induced papillary necrosis.

PMID- 10071420
TI  - Changes in insulin sensitivity, secretion and glucose effectiveness during
      menstrual cycle.
AB  - BACKGROUND: Several clinical conditions suggest an effect of sex steroids on
      glucose homeostasis in women. Studies examining this phenomenon have yielded
      controversial results. METHODS: To investigate the effect of the menstrual cycle
      on insulin sensitivity, glucose effectiveness and acute insulin response to
      glucose using the tolbutamide-modified intravenous glucose tolerance test (IVGTT)
      during the follicular (day 8 +/- 1) and luteal (day 23 +/- 1) phases of the
      menstrual cycle, the authors recruited 12 healthy regularly menstruating women.
      All had fasting glucose concentration of < 100 mg/dl [corrected] (89.7 +/- 6.2)
      with no family history of diabetes mellitus; their body mass indices were < 25
      kg/m2 (22.41 +/- 1.44 kg/m2). RESULTS: The mean insulin sensitivity (Si) values
      decreased during the cycle. Insulin sensitivity (Si x 10(-4)/min.mU/ml) was
      higher in the follicular phase (5.03 +/- 0.72) and decreased in the luteal phase
      (2.22 +/- 0.45) (p < 0.001). Glucose effectiveness (Sg min-1) did not change as a
      function of the phase of the menstrual cycle. Sg estimates were 0.0229 +/-
      0.00323 in the follicular phase, and 0.0225 +/- 0.00319 (p = NS) in the luteal
      phase, respectively. Acute insulin response (AIRg mU/ml) was 276.4 +/- 27.8 in
      the follicular phase. An adaptive increase (304.4 +/- 51.1) in response to the
      insulin resistance during the luteal phase was observed, but this increase was
      not statistically significant (p = NS). CONCLUSIONS: Knowledge of the variations
      in insulin sensitivity that occur during the normal menstrual cycle provides a
      basis of comparison for studies of other clinical conditions. Also, this
      phenomenon should be considered if the determination of insulin resistance is the
      purpose of certain epidemiological studies.

PMID- 10071421
TI  - Monitoring of molecular and cytogenetic damage in lymphocytes from three persons
      with polycystic kidney disease.
AB  - BACKGROUND: Much interest has been generated in the studies that would help to
      understand whether there is a causal association between disease and various
      types of molecular or cytogenetic damage detected in human cells. MATERIALS AND
      METHODS: The aims of this study were to elicit the possible association between
      DNA and cytogenetic damage induced in lymphocytes of three members of a family
      with autosomal dominant polycystic kidney disease (ADPKD). The predictability to
      develop cancer or to sensitive response to environmental exposure of the young
      girl at the age of 19, her brother (9 years old) and a maternal aunt at the age
      of 41 were sought. Cytogenetic studies, analysis of DNA damage by single cell gel
      electrophoresis assay (SCGE known as a Comet assay), and analysis of p21ras
      protein level in blood plasma were carried out on their lymphocytes. RESULTS: The
      analysis for presence of chromosome aberrations in the first mitosis and sister
      chromatid exchanges in the second mitosis revealed elevated levels of cytogenetic
      biomarkers when compared to the mean values observed in the reference group in
      environmental biological monitoring studies. Results of sister chromatid
      exchanges (SCE) and percent of cells with elevated number of exchanges (high
      frequency cells) that were significantly higher in two probands had demonstrated
      susceptibility to or possibility of environmental exposure (pesticides, smoking).
      The results of this study show that the lymphocytes of two persons revealed
      increased sensitivity to 0.5 Gy dose of gamma radiation expressed in the
      increased, although statistically insignificant, damage detected on the molecular
      level after cell irradiation. CONCLUSIONS: The latter might be associated with a
      specific aberration present in the cells of these persons. But final conclusions
      can be arrived at when an application of FISH technique is completed.

PMID- 10071422
TI  - Asymptomatic bacteriuria and inflammatory response to urinary tract infection of
      elderly ambulatory women in nursing homes.
AB  - BACKGROUND: Bacteriuria > or = 10(5) CFU/ml is evidence of urinary tract
      infection in the absence of associated signs or symptoms. The presence of pyuria
      with asymptomatic bacteriuria established the response of elderly women against
      microorganisms capable of causing invasiveness or tissue injury of the urinary
      tract. METHODS: The association between bacteriuria and pyuria was determined in
      178 elderly, ambulatory women without symptoms of urinary tract infection in
      seven nursing homes. Urine culture results were subsequently analyzed in
      conjunction with absolute leukocyte count in urine. In this cross-sectional
      study, asymptomatic bacteriuria in elderly women was classified with and without
      pyuria. RESULTS: The prevalence of asymptomatic bacteriuria was found in 44
      (24.7%) elderly women. The presence of pyuria had a sensitivity of 63.6% for
      bacteriuria and a specificity of 91%. The positive predictive value for the
      presence of pyuria predicting those with bacteriuria was 70%, and the negative
      predictive value for the absence of pyuria predicting those without bacteriuria
      was 88.4%. Escherichia coli was the most common organism isolated in 81.8% of the
      women. CONCLUSIONS: Bacteriuria > or 10(5) CFU/ml associated with pyuria was
      detected in 77% of elderly women with asymptomatic urinary tract infections.
      Bacteriuria of < 10(5) CFU/ml with pyuria proves less sensitive as an indicator
      of urinary tract infection. Elderly women with pyuria but without bacteriuria
      should be studied for other causes of urinary tract inflammation.

PMID- 10071424
TI  - Renovasculopathies of hypertension in Hispanic residents of Dallas, Texas.
AB  - BACKGROUND: Mean blood pressure levels (MBP) appear to rise with age slowly in
      the population of Mexico City and more swiftly in the U.S. in the black and white
      population, judging from published survey data. Some evidence suggests that MBP
      rises at intermediate rates in Hispanics in the U.S. METHOD: This question is
      explored here in two ways, by review of published survey data and by a novel
      approach that uses renal tissues obtained from forensic autopsies to estimate
      MBP. Past studies have revealed good agreement between the two methods of
      estimating MBP. RESULTS: Good agreement is again observed from the results of
      this study. Results from both methods agree that MBP is much lower at all ages in
      Mexican men and women than in blacks and whites in the U.S. Both methods also
      agree that Hispanics in the U.S. demonstrate an intermediate rise in MBP. A
      speculative first look at a small sample of U.S. Hispanics suggest that MBP rates
      of recent immigrants tend to resemble those of Mexico, while MBP levels of
      migrants of long-term residence resemble the native-born U.S. populations.
      CONCLUSIONS: The findings underscore the need for definitive testing to confirm
      if Mexicans who relocate to the U.S. may acquire an acceleration of the
      renovasculopathies, and of the lifelong progression toward hypertension that this
      implies.

PMID- 10071423
TI  - Transplant of cultured neuron-like differentiated chromaffin cells in a
      Parkinson's disease patient. A preliminary report.
AB  - BACKGROUND: Treatment of Parkinson's Disease (PD) has been attempted by others by
      transplanting either the patient's own adrenal medullary tissue or fetal
      substantia nigra into caudate or putamen areas. However, the difficulties
      inherent in using the patient's own adrenal gland, or the difficulty in obtaining
      human fetal tissue, has generated the need to find alternative methods. METHODS:
      We report here of an alternative to both procedures by using as transplant
      material cultured human adrenal chromaffin cells differentiated into neuron-like
      cells by extremely low frequency magnetic fields (ELF MF). RESULTS: The results
      of this study show that human differentiated chromaffin cells can be grafted into
      the caudate nucleus of a PD patient, generating substantial clinical improvement,
      as measured by the Unified Rating Scale for PD, which correlated with glucose
      metabolism and D2 DA receptor increases as seen in a PET scan, while allowing a
      70% decrease in L-Dopa medication. DISCUSSION: This is the first preliminary
      report showing that transplants of cultured differentiated neuron-like cells can
      be successfully used to treat a PD patient.

PMID- 10071425
TI  - Radiopharmacokinetics, renal clearance and dosimetry of 99mTc-MAG3.
AB  - BACKGROUND: Technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) is a
      radiopharmaceutical for tubular function and can be prepared with 99m-technetium
      and the ligand Bz-MAG3 (Instituto Nacional de Investigaciones Nucleares, Mexico
      City). No radiopharmacokinetic parameters have been found for the healthy adult
      Mexican population with 99mTc-MAG3, prepared with the nationally produced or
      imported Bz-MAG3 kit. METHODS: The radiopharmacokinetic parameters and the
      clearance of 99mTc-MAG3 in seven healthy Mexican volunteers were determined by
      the single- and multi-sample methods. Computer programs were used for the
      calculations. RESULTS: Using several plasma samples from 0-43 min and the BIEXP
      program, it was shown that 99mTc-MAG3 follows a two-compartment model of
      distribution, with an apparent volume in the central compartment Vdcc = 3.8 + 0.7
      l, a volume of distribution at steady state Vdss = 6.7 + 1.0 l, T1/2 alpha = 0.07
      + 0.02 h-1, T1/2 beta = 0.49 + 0.15 h-1, mean residence time MRT = 0.60 + 0.17 h
      and clearance = 208 + 57 (ml/min)/1.73 m2. In comparison, the clearance value
      with a single sample drawn 43 min post-injection and calculated with Tauxe's
      formula was 193 +/- 59 (ml/min)/m2. CONCLUSIONS: The 15 ml difference between the
      two methods is neither statistically different (p = 0.11) nor important for
      routine clinical studies. The single-sample method is recommended because it is
      reliable and can be done at the same time that the dynamic renal scan is
      acquired. Estimated absorbed radiation dose was calculated for several organs.

PMID- 10071426
TI  - Three treatment schemes with colloidal bismuth subcitrate (Q-ULCER) in peptic
      ulcer with Helicobacter pylori.
AB  - BACKGROUND: Since the discovery, several decades ago, of the infection of the
      gastric mucosa with Helicobacter pylori and its association with chronic antral
      gastritis and peptic ulcer, the treatment of ulcer illness has recently been
      revolutionized. METHODS: In this study, the clinical effectiveness of three
      schemes of treatment with colloidal bismuth subcitrate (CBS) were compared. Fifty
      three patients suffering from gastroduodenal peptic ulcer with Helicobacter
      pylori were distributed randomly into three groups. Group I (n = 17) received 240
      mg CBS every 12 h for 6 weeks. Group II (n = 17) received 240 mg CBS every 12 h
      for 6 weeks, pus metronidazole 500 mg every 8 h plus tetracycline 500 mg every 8
      h for 10 days. Group III (n = 19) received 240 mg CBS every 12 h for 6 weeks,
      plus metronidazole 500 mg every 8 h plus amoxicillin 750 mg every 12 h for 10
      days. A duodenoscopy investigation with antrum biopsy for a morphologic study and
      detection of the germ was carried out by means of urease test and histological
      study (Warthin-Sarry and hematoxylin-eosin). RESULTS: The three schemes of
      treatment were effective for ulcerous healing with 70.5%, 82.3%, and 78.2%,
      respectively, without significant differences. The highest clearing index (52.6%)
      was obtained in group III. CONCLUSIONS: With these treatments, the Helicobacter
      pylori eradication was only observed in 47.3% of the patients studied.

PMID- 10071427
TI  - Susceptibility to varicella-zoster infection in individuals 1 to 29 years of age
      in Mexico.
AB  - BACKGROUND: The prevalence of varicella zoster virus (VZV) infection has been
      poorly studied in Latin America. The aim of this work was to study the
      seroprevalence of antibody to VZV infection in Mexico. Infection was determined
      in 3,737 individuals. METHODS: Samples were collected during a national serologic
      survey performed during 1987-1988 and represented individuals 1- to 29-years-old
      from all socioeconomic levels and from rural and urban communities throughout the
      country. Antibodies anti-VZV were measured with a commercially available enzyme
      linked immunosorbent assay (VARELISA Merck, Germany). RESULTS: In the population
      studied, 464 individuals (12.4%) were seronegative or susceptible to infection,
      whereas about 17.0% of individuals 1- to 19-years-old were susceptible to
      infection. Between the ages of 20 to 24 years, 8.4% were susceptible and between
      25 to 29 years, 5.0% of persons were still susceptible to infection. CONCLUSIONS:
      Socioeconomic level, density of population, crowding, and gender were not found
      as risk factors for susceptibility to VZV infection in adolescents and young
      adults. Low educational level was found as a risk factor for susceptibility. High
      proportions of adolescents and young adults in Mexico are susceptible to VZV
      infection and should receive special attention when designing vaccination
      programs.

PMID- 10071428
TI  - Serologic evidences suggesting the presence of Borrelia burgdorferi infection in
      Mexico.
AB  - BACKGROUND: Lyme disease is the most common vector-borne human disease in Europe
      and the United States. In Mexico, clinical cases suggestive of Lyme borreliosis
      have been reported; however, infection was not confirmed by serologic or
      microbiologic tests. METHODS: To study the prevalence of IgG antibodies against
      Borrelia burgdorferi among Mexican persons, a community-based sero-survey
      including all states of Mexico was done. A sample of 2,890 sera representing
      individuals of all ages and all socioeconomic levels was studied. Antibodies anti
      B. burgdorferi were determined by enzyme-linked immunosorbent assay (ELISA) using
      a whole-cell sonicated extract of B. burgdorferi strain B31. Serum specimens
      positive for ELISA were further studied by Western blot (WB). A serum sample was
      considered positive by WB if at least three of the following protein bands were
      recognized: 18, 24, 28, 29, 31, 34, 39, 41, 45, 58, 62, 66, and 93 kDa. Some WB
      positive specimens were further confirmed with an immunodot-blot (IDB) test using
      recombinant and purified B. burgdorferi proteins. RESULTS: Of the 2,890
      specimens, 34 were positive for ELISA; nine of these 34 were confirmed as
      positive by WB. Four of the nine WB positive sera were tested by IDB and all four
      were positive. The prevalence of WB confirmed cases in the sample studied was
      0.3%. Positive specimens were from residents of the northeastern and central
      areas of Mexico. CONCLUSIONS: The serological evidences of this study suggest
      that Borrelia burgdorferi infection is present in the Mexican population. This
      finding should be confirmed by documenting the infection in clinical cases and in
      tick vectors.

PMID- 10071429
TI  - Anti-inflammatory activity of Debaryomyces hansenii Cu,Zn-SOD.
AB  - BACKGROUND: Cu,Zn-superoxide-dismutase, Cu,Zn-SOD, can be obtained from different
      sources with different anti-inflammatory activities. In this study we compared
      the anti-inflammatory capacity of the marine yeast Debaryomyces hanseii Cu,Zn-SOD
      (Dh-SOD) with that of bovine erythrocytes (Be-SOD) in a preventive and a
      therapeutic fashion. METHODS: Edema was induced by carrageenan injection into the
      rat hind paw and was evaluated using a mercury plethysmograph. Development of the
      inflammatory process was followed by volume displacement at time 0 (carrageenan
      injection), 1, 2, 3, 4, 5, 6, 9, 12, and 24 h thereafter. Three different SOD
      doses were used in preliminary experiments to prevent edema: 10, 100, and 1,000
      U/kg. RESULTS: The results indicate that, at the lowest dose (10 U/kg), both SOD
      samples are effective in reducing inflammation in both the prostaglandin and
      amplification phases (-24.8% and -17.5% in the case of Be-SOD, and 11.8% and 
      18.7% in the case of Dh-SOD, respectively) (p < 0.05). At 100 U/kg, Be-SOD also
      shows good anti-inflammatory activity in all edema phase (-27.1% in the serotonin
      phase; -19.4% in the prostaglandin phase; and -20% in the amplification phase) (p
      < 0.05), but Dh-SOD was less effective (-10.9%, -9.1%, and -5.7%). At the highest
      dose tested (1000 U/kg), Dh-SOD was, again, more effective than Be-SOD in all
      three edema phases (-33.1% and -1.5%; -17.9% and -2.6%; and -13.8% and 6.7%,
      respectively) (p < 0.05). When evaluated as a therapeutic alternative, single
      doses of Dh-SOD at 1,000 U/kg, and Be-SOD at 100 U/kg, both showed good anti
      inflammatory activities (-31.7% and -23.5%, respectively) (p < 0.05). CONCLUSION:
      For therapy purposes alone, Dh-SOD appears to be a better anti-inflammatory agent
      than Be-SOD in carrageenan-induced edema.

PMID- 10071431
TI  - New horizons in the fight against breast cancer.

PMID- 10071430
TI  - Thyrotoxic periodic paralysis in Mexican mestizo patients: a clinical,
      biochemical and HLA-serological study.
AB  - BACKGROUND: Thyrotoxic periodic paralysis (TPP) is characterized by episodes of
      neuromuscular weakness occurring in the context of hypokalemia and
      hyperthyroidism and has been predominantly described in Oriental populations.
      Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of
      Native American descent. The objective was to analyze the clinical, biochemical,
      and HLA characteristics of a group of Mexican mestizo patients with TPP. METHODS:
      The sample was comprised of 14 men with TPP diagnosed since January 1990, based
      on one or more episodes of flaccid paralysis, accompanied by hypokalemia and
      occurring in the context of clinical and biochemical hyperthyroidism. Eight were
      available for HLA testing. RESULTS: Hyperthyroidism was diagnosed before the
      development of periodic paralysis in five of the patients, whereas in six it
      occurred afterward. The severity of paralysis did not correlate with the degree
      of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was
      found in Graves' patients without paralysis but not in those with paralysis, as
      compared to the general population. CONCLUSIONS: TPP is more common than
      previously thought in Mexicans, in whom it behaves as in other Native American
      groups. The lack of HLA-DR3 association in Graves' patients with TPP is
      interesting, but at the moment has no pathophysiological implications.

PMID- 10071432
TI  - The role of sentinel node biopsy in breast cancer.

PMID- 10071433
TI  - Epidemiology of breast cancer in Connecticut women.
AB  - At least 50% of breast cancer may be "explained" by known or suspected risk
      factors, including modifiable behaviors involving diet, overweight, exercise, and
      alcohol use. Interest continues to grow in "hereditary" breast (and ovarian)
      cancer due to germ cell mutations, but most breast cancers are due to
      environmentally induced (somatic) mutations. According to data from the
      Connecticut Tumor Registry, the incidence of invasive breast cancer has changed
      little since 1990. The proportion of breast cancers diagnosed at the in situ
      stage has increased while the proportions diagnosed at the regional and distant
      stages have decreased, which is consistent with an effect of increased screening.
      Breast cancer mortality rates, the crucial yardstick of progress in cancer
      control, have declined slightly in Connecticut (and nationally) since 1989,
      reflecting the effects of earlier detection (through screening) and improved
      treatment. Primary care physicians have an important role in primary and
      secondary prevention.

PMID- 10071434
TI  - A comprehensive breast and cervical cancer screening program for medically
      underserved women in Connecticut.
AB  - A comprehensive breast and cervical cancer early detection program supported by
      federal and state funds and administered by the Connecticut Department of Public
      Health, is actively recruiting and screening older, uninsured, low income women
      at contracted health-care facilities throughout the state. The program provides
      diagnostic testing, treatment referral, outreach, and educational activities.
      During the first 27 months of the program, 5,509 women were enrolled and
      screened. Women were recruited primarily through media sources and
      physician/nurse referrals. The majority of women served were non-Hispanic white,
      between ages 40 to 59, with annual incomes of less than $10,000, and a high
      school education or less. Some 62% of enrolled women either never had a mammogram
      or did not have a repeat mammogram within the time-frames recommended by ACS.
      Recruitment efforts continue to enroll medically underserved women for breast and
      cervical cancer screening services. Future efforts will focus on rescreening in
      order to achieve the program's overall mission of detecting breast and cervical
      cancers at earlier stages.

PMID- 10071435
TI  - Breast imaging.

PMID- 10071436
TI  - Systemic adjuvant therapy of breast cancer.
AB  - Following local excision, the prognosis for long-term cure of a patient with
      breast malignancy depends on the presence of micro-metastatic disease. The risk
      of occult disease present prior to removal of the primary tumor can be assessed
      by knowledge of the tumor size, histology and degree of differentiation, and
      spread to axillary nodes. It ranges from 25% in node-negative tumors to as much
      as 75% to 80% in the presence of multiple involved nodes. Systemic therapy can
      reduce the risk by approximately one-third. Present studies indicate that
      regardless of age or menopausal status the majority of women should be considered
      for chemotherapy (if hormone receptor negative) or chemotherapy and tamoxifen
      (receptor positive). However, it is hoped that further refinement of our
      knowledge of prognostic factors will allow better design of adjuvant therapy
      through better understanding of the mechanisms of tumor growth and spread.

PMID- 10071437
TI  - Psychological aspects of breast cancer.
AB  - This paper reviews the common psychological concerns expressed by women with
      breast cancer. It also reviews the epidemiology of psychiatric diagnoses in this
      population. The special diagnostic problems and available pharmacological and
      psychotherapeutic interventions are discussed. The aim of psychiatric treatment
      in breast cancer patients is to relieve major psychological symptoms as well as
      to address underlying intrapsychic conflicts that become prominent during
      treatment.

PMID- 10071438
TI  - High-dose chemotherapy for the treatment of high-risk and advanced breast cancer.

PMID- 10071439
TI  - Integrative medicine: an old concept with new meaning.

PMID- 10071440
TI  - Braintrust.

PMID- 10071441
TI  - Reflections on Y2K.

PMID- 10071442
TI  - [Ethical developments in medically assisted fertility].

PMID- 10071443
TI  - [Humanity and cloning, a therapeutic tool or a dream of immortality?].

PMID- 10071444
TI  - [Hormones and sexuality in the young and aging woman].

PMID- 10071445
TI  - [Medical treatment of infertility: therapeutic guide. I. In women].

PMID- 10071446
TI  - [Carcinoma in situ of the testis in infertile men. Experience in a medically
      assisted reproduction program].
AB  - Three cases of carcinoma in situ were found by testicular biopsy among a group of
      85 infertile men, most with diagnosed azoospermia. It remains difficult and
      unclear how to manage such patients to achieve offspring and to assure the
      adequate oncological therapy.

PMID- 10071447
TI  - [Deimons-Meigs syndrome and elevated CA-125: diagnosis of ovarian cancer and
      therapeutic implications].
AB  - Regarding a original observation of the Deimons-Meigs syndrome, the authors have
      derived, from a review of the literature, the main clinicals and etiopathogenics
      characteristics, and tried to discuss the terms and conditions of a therapeutic
      treatment appropriate to such a situation.

PMID- 10071448
TI  - [Relevance of surgical lymph node staging for malignant ovarian germ cell
      tumors].
AB  - BACKGROUND: The purpose of the study was to investigate the relevance of
      infrarenal paraaortic lymph node staging in the surgical procedure of malignant
      ovarian germ cell tumors in adults. METHODS: 84 cases (39 dysgerminoma, 45
      nondysgerminatous tumors) were studied by means of a retrospective multicentric
      survey. RESULTS: Among the tumors limited to the ovaries, 36 were not completely
      staged, in particular the infrarenal paraaortic lymph nodes had not been
      explored. Disease recurred in 6 of these non-staged cases: 3 recurrences arose
      from the lymph nodes, and 2 patients died. However no recurrence was noted among
      the 13 patients who underwent complete surgical staging (statistically non
      significative). We observed the same tendency among patients with advanced tumors
      that required complete peritoneal excision: there was no recurrence among the 6
      patients having undergone lymph node dissection, whereas recurrence was noted in
      2 of the 10 cases without lymph node dissection, one of which resulted in the
      death of the patient (statistically non-significative). CONCLUSION: In order to
      classify a tumor as stage I, it is essential that infrarenal lymph node
      dissection be performed, given the frequency of lymphatic involvement. Only then
      can the patient benefit from conservative surgery, possibly without any further
      treatment. The prognosis of advanced tumors that call for complete
      intraperitoneal excision also seems to be improved by retroperitoneal lymph node
      dissection. It can be carried out secondarily by laparoscopy, in which case
      chemotherapy can be quickly performed, as this type of surgery causes little
      morbidity.

PMID- 10071449
TI  - [Pelvic tumoral actinomycosis: a difficult diagnosis. Two case reports].
AB  - Two cases of intra-uterine device-associated occlusive pelvic pseudo-tumoural
      actinomycosis are presented. A pre-operative diagnosis of ovarian carcinoma was
      considered in both cases and lead to a wide and difficult surgery. Actinomycosis
      was confirmed by the postoperative histopathologic examination, and the patients
      were successfully treated with penicillin. The difficulties and limits of the
      clinical and histopathological diagnosis are exposed. The interest of the pre and
      intra-operative diagnosis which can avoid an extensive surgery with high
      morbidity is highlighted.

PMID- 10071450
TI  - [Cushing's syndrome and pregnancy: a case report and review of the literature].
AB  - The association between pregnancy and Cushing syndrome is extremely rare. The
      diagnosis of Cushing syndrome during pregnancy is rendered difficult by
      hyperoestrogenic state that alters many of the classical tests. An early and
      precise diagnosis with adequate management will allow us to reduce maternal and
      fetal risks.

PMID- 10071451
TI  - [Gestational trophoblastic tumors: epidemiology and prognosis in Dakar University
      teaching hospital].
AB  - From a prospective and length wise survey, the forecast of the gestational
      trophoblastics tumours was estimated. Between 1st November 1996 and 31st October
      1997, 102 cases of gestational trophoblastics tumours was registered. The medium
      profile was a "Ouoloff" (54%) or "Serere" (20%), 30 years old, multiparous,
      without, security social cover (100%). Looking back over 2 to 12 months, 25% of
      cases has worthily grown; so 10% of cases of choriocarcinoma with 3 death. The
      average cost of post-molar follow-up was about 120,000 F CFA. Because of the
      expensive cost of antimitotics, between 180,000 and 278,000 F CFA, their
      availability wasn't frequent and their use was restricted.

PMID- 10071452
TI  - t(9;14)(p13;q32) involving the PAX-5 gene: a unique subtype of 14q32
      translocation in B cell non-Hodgkin's lymphoma.
AB  - Newly identified t(9;14)(p13;q32) is a subtype of the well-defined 14q32
      translocation and is closely associated with lymphoplasmacytic lymphoma (Revised
      European-American Classification of Lymphoid Neoplasms). The analysis of the
      breakpoint of t(9;14) unraveled its molecular structure as being the
      recombination of the PAX-5 gene on 9p13 with IgH locus located on 14q32. The
      molecular event does not seem to cause structural alteration of the protein
      product of PAX-5 and, instead, its deregulation is most likely the essential
      outcome of this translocation. In vitro experiments have shown that the
      overexpression of PAX-5 resulted in enhanced proliferation of B cells,
      implicating its potential capacity for lymphomagenesis. PAX-5 is crucial during
      most developmental stages of B cells mainly through regulating the expression of
      a variety of genes. Therefore, elucidating the nature of the altered expression
      of these downstream genes as well as the PAX-5 gene itself would be indispensable
      in clarifying the precise mechanism of lymphomagenesis caused by t(9;14).

PMID- 10071453
TI  - The role of accessory cells in allogeneic peripheral blood stem cell
      transplantation.
AB  - Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood
      mononuclear cells (G-PBMC) have been used increasingly to reconstitute
      hematopoiesis after myeloablative therapy in allogeneic transplantation. Compared
      with conventional bone marrow, faster engraftment is consistently observed with G
      PBMC, with differences more pronounced in platelet than in neutrophil recovery. G
      PBMC contain not only severalfold more CD34+ cells than bone marrow but also, on
      average, 50-fold more monocytes, which may stimulate stromal cell function and
      facilitate engraftment. Although G-PBMC also contain 10-fold more T cells, the
      incidence and severity of acute graft-vs.-host disease (GVHD) is no higher than
      that observed in allogeneic bone marrow transplantation. Hypothetically, these
      clinical observations can be explained by the direct effect of G-CSF on T cell
      function as demonstrated by polarization of T cells expressing the T helper type
      2 (Th 2) cytokine interleukin (IL)-4 in the murine model. Alternatively, G-PBMC
      may contain cells that actively suppress donor T cell responsiveness. Recent
      reports indicate that the large number of CD14+ monocytes in G-PBMC can suppress
      donor T cell proliferation in vitro. This effect may be attributable to both the
      increased ratio of CD14+:CD3+ cells in G-PBMC and the evidence that CD14+ cells
      in G-PBMC have decreased expression of both B7.2 and HLA-DR. There is some
      indication that natural killer (NK) cell number and function may be augmented in
      G-PBMC, which could have a favorable impact on the graft-vs.-leukemia (GVL)
      effect. Therefore, both the CD34+ and accessory cell content of G-PBMC may be
      important in early engraftment by controlling acute GVHD and facilitating GVL.

PMID- 10071454
TI  - Prevalence of anemia in Japanese adolescents: 30 years' experience in screening
      for anemia.
AB  - Iron deficiency is the most common cause of anemia in adolescents and is of
      continuing concern in Japan. We have conducted screening for anemia in
      adolescents in the Tokyo area since 1966. Screening for the prevalence of anemia
      is important both for identifying populations at risk and determining the
      appropriate treatment for individual patients. The number of junior and senior
      high school students enrolled in the screening program was 793 in 1966, which
      increased to more than 70,000 by 1989. A normal hemoglobin (Hb) level was present
      in 90% of students before 1981, and in 98% of boys and 95% of girls in 1990. The
      percentage of girls with a normal Hb level has decreased gradually since 1991.
      The high incidence of mild hypochromic microcytic anemia suggests an increase in
      the prevalence of iron deficiency. Dieting may be the cause of this undesirable
      phenomenon in adolescents.

PMID- 10071455
TI  - Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef
      sodium and tobramycin in febrile neutropenic patients with hematological
      malignancies. Kan-etsu Hematological Disease and Infection Study Group.
AB  - The clinical effects of concomitant use of granulocyte-colony stimulating factor
      (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were
      evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile
      episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium
      and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent
      response) or at day 7 (good response) was deemed effective. Among 157 evaluable
      episodes, the observed excellent responses were 31 (38.8%) and the good responses
      were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%)
      and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the
      G-CSF group and 66.2% (51/77) in the control group (not significant). The initial
      neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/-
      0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and
      0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G
      CSF does not affect the rate of response to empiric antibiotic therapy in febrile
      neutropenic patients, although a significant effect of G-CSF was observed on
      neutrophil recovery.

PMID- 10071456
TI  - Blast crisis of chronic myelogenous leukemia exhibiting immunophenotypic features
      of a myeloid/natural killer cell precursor.
AB  - We report a patient with Philadelphia chromosome (Ph1)-positive chronic
      myelogenous leukemia (CML) which transformed into blast crisis bearing the
      immunophenotypic features similar to those of the myeloid/natural killer (NK)
      cell precursor leukemia we proposed previously. Using a CD45 blast gating method,
      the myeloperoxidase-negative blasts were positive for CD7, CD13, CD33, CD34,
      CD56, and HLA-DR, but no other lymphoid antigens. Southern blot analysis showed
      germ line T cell receptor beta and delta genes and immunoglobulin heavy and light
      chain genes. Although NK cell blastic transformation with Ph1 positive CML has
      been reported in a single patient, this is, to our knowledge, the first report of
      CML blast crisis of myeloid/NK cell precursor origin.

PMID- 10071457
TI  - CD4/CD8 double-positive adult T cell leukemia with preceding cytomegaloviral
      gastroenterocolitis.
AB  - We present a rare case of adult T cell leukemia (ATL) in which leukemic T cells
      simultaneously expressed CD4 and CD8 surface antigens and refractory
      cytomegalovirus (CMV)-induced gastroenterocolitis preceded its clinical onset. A
      40-year-old male was admitted to our hospital with abdominal pain and bloody
      stool. Biopsy specimens of the gastric and rectal mucosa indicated CMV-induced
      gastroenterocolitis. The patient also proved to be seropositive for human T
      lymphotropic virus type I (HTLV-I). While being administered gancyclovir for CMV
      infection, he presented hepatomegaly and systemic lymphadenopathy. Monoclonal
      expansion of lymphoid cells integrated with HTLV-I genome was observed. He
      underwent a LSG15 regimen and hepatomegaly and lymphadenopathy improved markedly.
      Gastroenterocolitis also improved, but the symptoms did not disappear completely.
      CMV-induced diseases are prevalent among immunosuppressed patients. Although
      there was no evidence that this patient had ATL on admission, it is likely that
      he was severely immunodeficient. CMV can easily infect damaged mucosa. ATL cells
      often infiltrate gastrointestinal mucosa and may have triggered CMV
      gastroenterocolitis in this case.

PMID- 10071458
TI  - Hodgkin's disease following extranodal marginal zone B-cell lymphoma in
      remission.
AB  - A patient who developed Hodgkin's disease after an 11-year remission of marginal
      zone B-cell (MZB) lymphoma (low grade B-cell lymphoma of mucosa-associated
      lymphoid tissue type) is presented. Except for L26/CD20 expression by Reed
      Sternberg cells, morphologic, immunophenotypic, and genotypic findings were
      compatible with the diagnosis of Hodgkin's disease. The relationship between
      Hodgkin's disease and the preceding MZB lymphoma in this patient is discussed.

PMID- 10071459
TI  - Two separate episodes of hemophagocytic syndrome at a two-year interval in an
      apparently immunocompetent male.
AB  - We describe two separate episodes of hemophagocytic syndrome (HPS) at an interval
      of two years in a seemingly immunocompetent male. This case suggests the possible
      existence of an inherent predisposition to HPS, in which otherwise negligible
      self-limited viral infection may trigger HPS. Laboratory data for a 16-year-old
      boy admitted with persistent high grade fever and severe thrombocytopenia
      disclosed coagulation abnormality, liver damage, and hypercytokinemia. A bone
      marrow aspiration revealed a proliferation of histiocytes with fresh
      hemophagocytosis. We diagnosed that he was suffering from HPS. Responding to
      steroid pulse therapy, he recovered completely and was discharged. After two
      years of healthy life, he became febrile again and was readmitted. The fever was
      refractory to antibiotics and was associated with a sudden drop in platelet
      count. Laboratory data and the bone marrow picture were consistent with those of
      HPS. He was again successfully treated with steroid. After the second episode, he
      has been healthy for more than two years.

PMID- 10071460
TI  - Use of PCR serum in diagnosing and monitoring cytomegalovirus reactivation in
      bone marrow transplant recipients.
AB  - We previously reported that the use of polymerase chain reaction (PCR) in
      detecting cytomegalovirus (CMV) DNA in serum (sPCR) enables the detection of CMV
      viremia, which has not been possible with other methods. In this study, the
      clinical usefulness of sPCR was investigated by comparison with the results of
      three other diagnostic methods, i.e., antigenemia assay (AG), shell vial culture
      test (shell vial), and complement-fixing (CF) antibody titer. The present study
      included 26 patients with hematological diseases who had undergone allogeneic
      bone marrow transplantation (BMT). A total of 347 samples were collected, and the
      results of the sPCR and AG methods were in agreement in 91.1% of the samples.
      When a subject was positive in both the sPCR and AG tests, and the other two
      tests (shell vial and CF) were also positive, CMV reactivation was surmised as
      definite. When only the result of the shell vial test or the CF test was
      positive, these results were taken as false-positives. The time at which the
      samples became positive in each of these four tests was 7.5 weeks post-BMT for
      sPCR, 7.0 weeks post-BMT for the AG test, 7.4 weeks post-BMT for the shell vial
      test, and 9.7 weeks post-BMT for the CF test. Thus, it was found that samples
      became positive at almost the same time for the sPCR, AG, and shell vial tests.
      Interstitial pneumonitis (IP) due to CMV developed in 3 subjects. These cases
      were positive in the sPCR, AG, and shell vial tests prior to the manifestation of
      symptoms of IP. The CF test did not become positive until after the onset of the
      disease. As the IP due to CMV was controlled with treatment, the sPCR and AG
      tests became negative. With the shell vial and CF tests, on the other hand, the
      test results continued to be positive even after the IP was cured. These findings
      demonstrate that the sPCR test method--like the AG test--yields few false
      positive results. Therefore, the sPCR method is useful in early diagnosis of
      reactivation of CMV and for evaluation of the efficacy of therapy administered
      for IP. In addition, sPCR can be performed simultaneously on a large number of
      samples, and the evaluation of the test results is simple. We conclude that the
      sPCR test may be superior to the three other diagnostic methods for evaluation of
      serum samples from multiple institutions.

PMID- 10071461
TI  - Immune response of post-transplant peripheral lymphocytes against the patient pre
      B cell line, NAGL-1.
AB  - We have established a pre-B acute lymphoblastic leukemia (ALL) cell line, NAGL-1,
      from the bone marrow of a patient diagnosed with pre-B ALL. The patient has been
      disease-free for the 4 years since allogeneic bone marrow transplantation from
      her HLA-genotypically identical sister. NAGL-1 showed a pre-B cell phenotype
      (CD19+, CD10+, c mu+, s mu-) mostly identical to freshly isolated leukemic cells
      from the patient. This cell line strongly expressed HLA class I and HLA-DR
      molecules, as well as the costimulatory molecules CD54, CD40, and CD86. Cytotoxic
      T-lymphocyte (CTL) lines were generated by stimulating the donor-derived
      peripheral blood mononuclear cells with either irradiated leukemic cells or NAGL
      1. Both CTL lines showed specific lysis against NAGL-1 in 51Cr release assays.
      Lytic activity was partially inhibited by anti-CD8 and anti-HLA class I
      monoclonal antibodies. Treatment of NAGL-1 with TNF-alpha increased its
      susceptibility to the CTL line. One CD8+ T cell clone derived from the CTL line
      killed both the patient phytohemagglutinin (PHA) blasts and NAGL-1 but not the
      donor PHA blasts, suggesting that the clone recognized the patient-specific minor
      antigen presented on both PHA blasts and NAGL-1. Utilization of leukemic cell
      lines could be a useful model for the development of CTL lines and clones for
      immunological study and potential immunotherapy.

PMID- 10071462
TI  - Platelet activating factor causes a rapid increase in activity of prior expressed
      tissue factor on monocyte surface membrane.
AB  - It is known that tissue factor (TF) activity depends on cell membrane
      phospholipids. However, the mechanism involved in the regulation of TF activity
      by the modulation of the phospholipids has not yet been described in detail. To
      determine whether some mediators regulate TF activity by such a mechanism, we
      investigated the effect of platelet activating factor (PAF). Addition of PAF to
      TF-expressed monocytes caused a rapid and marked increase in the activity, but no
      increase in the antigen. Kinetic analyses were performed on TF-expressed
      monocytes with or without the addition of PAF, and on purified TF. The former
      revealed that the activity enhancement by PAF was associated with reduced Km,
      with Vmax remaining unaltered. The latter showed that the additional
      phosphatidylserine produced greater TF activity in purified TF, with an
      alteration pattern of kinetic parameters similar to that observed in the addition
      of PAF. From these results, we conclude that PAF regulates TF activity at the
      cell surface by alteration of the phospholipid composition of the membrane, and
      not by fresh production of TF apoprotein. The role of PAF as described in this
      paper must be one of the major regulatory systems in TF activity.

PMID- 10071463
TI  - Molecular characterization of total kininogen deficiency in Japanese patients.
AB  - Kininogens are multifunctional plasma glycoproteins. There are two forms of human
      kininogen: low molecular weight kininogen (LK) and high molecular weight
      kininogen (HK). Both are derived from the same gene by alternative splicing. Some
      patients with kininogen deficiency have been reported to be deficient only in HK
      while others are deficient in both HK and LK (total kininogen deficiency). We
      analyzed three Japanese patients with total kininogen deficiency by the Csp45I
      digestion study of exon 5 as previously reported in Williams trait and found that
      two had the same point mutation of C to T at base 22 of exon 5, resulting in a
      transition of CGA (Arg) codon to TGA (Stop) codon. This is the first report of
      molecular characterization of total kininogen deficiency in the Japanese
      population.

PMID- 10071464
TI  - Life-threatening bleeding in a case of autoantibody-induced factor VII
      deficiency.
AB  - A male patient presented with life-threatening bleeding induced by autoantibody
      induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria,
      skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing
      disturbed respiration. He developed acute renal failure and acute hepatic
      failure, probably due to obstruction of the ureters and the biliary tract,
      respectively. Although activated partial thromboplastin time was normal,
      prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0
      seconds in a normal control. Both the immunoreactive level of F.VII antigen and
      the F.VII activity of the patient's plasma samples were < 1.0% of normal.
      Although an equal part of normal plasma was added to the patient's plasma, PT was
      not corrected. The patient's plasma inhibited F.VII activity. These findings
      suggested the presence of a plasma inhibitor for F.VII. After administration of
      large doses of methylprednisolone, PT was gradually shortened and plasma levels
      of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic
      failure improved markedly following the steroid treatment. These observations
      suggest that life-threatening bleeding can be induced by autoantibody-induced
      F.VII deficiency and that immunosuppressive therapy using large doses of steroid
      can be successful in inhibiting the production of the autoantibody.

PMID- 10071465
TI  - Thermal cycling procedures for laboratory testing of dental restorations.
AB  - OBJECTIVES: Exposure of restorations in extracted teeth to cyclic thermal
      fluctuations to simulate one of the many factors in the oral environment has been
      common in many tracer penetration, marginal gap and bond strength laboratory
      tests. Temperature changes used have rarely been substantiated with temperature
      measurements made in vivo and vary considerably between reports. Justification
      and standardization of regimen are required. DATA, SOURCES AND STUDY SELECTION:
      An assessment of reports describing temperature changes of teeth in vivo is
      followed by an analysis of 130 studies of laboratory thermal cycling of teeth by
      99 first authors selected from 25 journals. A clinically relevant thermal cycling
      regimen was derived from the in vivo information, and is suggested as a benchmark
      standard. CONCLUSIONS: Variation of regimens used was large, making comparison of
      reports difficult. Reports of testing the effects of thermal cycling were often
      contradictory, but generally leakage increased with thermal stress, although it
      has never been demonstrated that cyclic testing is relevant to clinical failures.
      However, should this be done, the standard cyclic regimen defined is: 35 degrees
      C (28 s), 15 degrees C (2 s), 35 degrees C (28 s), 45 degrees C (2 s). No
      evidence of the number of cycles likely to be experienced in vivo was found and
      this requires investigation, but a provisional estimate of approximately 10,000
      cycles per year is suggested. Thermal stressing of restoration interfaces is only
      of value when the initial bond is already known to be reliable. This is not the
      case for most current restorative materials.

PMID- 10071466
TI  - The effect of parabens in a mouthwash and incorporated into a sustained release
      varnish on salivary bacteria.
AB  - OBJECTIVES: The purpose of this study was to evaluate the antimicrobial efficacy
      of parabens, in a mouthwash and in a slow release device, against cariogenic
      bacteria in the oral cavity. METHODS: Parabens were formulated in a mouthwash or
      in a topical slow release varnish preparation. In two separate studies,
      volunteers were asked to use the mouthwash or the slow release varnish applied in
      a personal night guard device. The levels of mutans streptococci (MS),
      Lactobacilli (LB) and total cultivated bacteria were measured before and after
      using the mouthwash or the slow release varnish. RESULTS: The mouthwash
      containing parabens had a minor and a short-term effect on MS and LB counts in
      human saliva. The use of slow release varnish containing parabens, applied in a
      night guard, had a prolonged antibacterial effect on both MS and LB counts.
      CONCLUSIONS: Parabens in a mouthwash had little effect on oral bacteria counts;
      however, paraben in the slow release device had a significant and an extended
      effect in reducing oral bacteria. Although substantial reductions in oral
      bacterial counts were recorded after the use of parabens in a slow release
      device, this effect could probably be enhanced by an improved pharmaceutical
      formulation.

PMID- 10071467
TI  - Bioactivity of pseudowollastonite in human saliva.
AB  - OBJECTIVES: Pseudowollastonite (CaO.SiO2) was found to be bioactive in a
      simulated body fluid environment. In the present study, 'in vitro' bioactivity of
      pseudowollastonite was further assessed in human parotid saliva. The main
      objective was to compare behaviour of the material in a natural medium of high
      protein content (human parotid saliva) with its behaviour in an acellular protein
      free solution (simulated body fluid). METHODS: Samples of polycrystalline
      pseudowollastonite were immersed for one month in human parotid saliva at 37
      degrees C. Changes in ionic concentrations in the human parotid saliva and the pH
      right at the interface of pseudowollastonite/human parotid saliva were
      determined. The products of the interfacial reactions were studied by thin-film X
      ray diffraction, scanning and transmission electron microscopy. RESULTS: The
      results confirmed formation of a hydroxyapatite-like layer on the surface of the
      material, and also suggested that the mechanism of hydroxyapatite-like layer
      formation in saliva was similar to that showed in simulated body fluid.
      CONCLUSIONS: The hydroxyapatite-like layer formed at the interface was found to
      be compact, continuous and composed of many small crystallites with
      ultrastructure similar to that of natural cortical bone and dentine. The study
      also concluded that the high pH conditions (10.32) existing right at the
      pseudowollastonite/human parotid saliva interface promoted hydroxyapatite-like
      precipitation. At this stage of the study, similarities of the material behaviour
      in saliva and acellular simulated body fluid suggest that the pseudowollastonite
      could be of interest in specific periodontal applications for bone restorative
      purposes.

PMID- 10071468
TI  - Salivary sialic acid, protein, salivary flow rate, pH, buffering capacity and
      caries indices in subjects with Down's syndrome.
AB  - OBJECTIVES: The aim of this study was to compare salivary sialic acid, protein,
      salivary flow rate, pH and buffering capacity and caries indices between subjects
      with Down's Syndrome and healthy controls. METHODS: Unstimulated mixed saliva was
      collected from 26 Down's syndrome subjects and 25 healthy subjects of age range 6
      24 years. Total protein was determined by the method of Lowry and total sialic
      acid using Ehrlich reagent. Laemmli SDS-polyacrylamide gel electrophoresis was
      also carried out. RESULTS: Buffering capacity and pH were quite similar for both
      groups. For permanent dentition subjects pH was significantly higher (P = 0.03)
      in the Down's syndrome group. The salivary flow rate of the Down's syndrome
      subjects was significantly lower (P < 0.01) than that of healthy controls and the
      Down's syndrome subjects' salivary protein and sialic acid levels were
      significantly higher (P < 0.001). The ratios of total sialic acid to total
      protein were significantly higher (P < 0.001) in the Down's syndrome group.
      However, salivary sialic acid expectoration rates, a means of compensating for
      flow rate differences, were significantly lower (P = 0.01) in the Down's syndrome
      subjects than in controls. Electrophoresis revealed no significant differences
      between the protein bands of the groups. There were no significant differences in
      caries indices between groups, even when compensated for age, nor in the salivary
      parameters within groups between sexes. CONCLUSIONS: Total salivary sialic acid
      in Down's syndrome subjects, higher in terms of levels but lower in terms of
      expectoration rates, was significantly different from that of controls of similar
      caries indices.

PMID- 10071469
TI  - Marginal adaptation of direct composite and sandwich restorations in Class II
      cavities with cervical margins in dentine.
AB  - OBJECTIVES: The aim of this study was to evaluate the marginal adaptation of
      direct Class II sandwich restorations with resin-modified glass-ionomer cements
      and compomers in comparison to base and total bond restorations. For sandwich
      restorations with a triple cure resin-modified glass-ionomer cement the influence
      of different light curing techniques was also evaluated. METHODS: Large butt
      joint class II cavities with cervical margins 1 mm below the cemento-enamel
      junction were cut into 120 extracted human molars. The cavities (15 groups, n =
      8) were filled using a sandwich, base or total bond technique with materials from
      five different manufacturers. A three-sited light curing technique was used in 13
      groups. For the material combination Vitremer/Z100 two additional groups with a
      different wand positioning and a metal matrix were evaluated. After water storage
      for 21 days and thermocycling (2000x, 5-55 degrees C), replicas were
      quantitatively analysed in the SEM. Statistical analysis was performed with the
      Kruskal-Wallis test and the Bonferroni test at p < 0.05. RESULTS: The marginal
      adaptation of vertical enamel margins was not dependent on the restorative
      technique. For margins in dentine, marginal adaptation was significantly better
      with the sandwich technique than with a base or total bond technique for all
      materials. There were no significant differences between the base and total bond
      technique. Overall, resin-modified glass-ionomer cements showed somewhat better
      results than compomers in sandwich restorations, though differences were not
      significant for some criteria. Vitremer/Z100 sandwich restorations applied with a
      metal matrix showed the highest mean percentage of excellent margins of all
      experimental groups. CONCLUSIONS: Both resin-modified glass-ionomer cements and
      compomers can improve the marginal quality when used in a sandwich technique.
      Further research is necessary to determine the ideal material combination for
      sandwich restorations.

PMID- 10071470
TI  - An investigation of the variables which may affect the bond between plastic teeth
      and denture base resin.
AB  - OBJECTIVES: The failure of the bond between acrylic resin denture base material
      and resin teeth remains a significant problem. This study evaluated the tensile
      bond strength of specimens produced by commonly employed tooth preparation and
      processing methods as used in dental laboratories. METHODS: Twenty-two
      experimental groups, each consisting of 36 specimens, were investigated by
      subjecting the tooth-resin bond to tensile loading. The groups were allocated to
      one of five experimental sets to investigate: (a) effect of resin dough time, (b)
      effect of tooth surface condition, (c) effect of processing variables, (d) effect
      of monomer cementing, and (e) effect of acrylic resin cement. The results were
      analysed statistically using a one factor ANOVA and a Student t test. RESULTS: A
      significantly stronger bond was obtained when the resin was packed late in the
      dough stage, and a superior bond, in all cases, when high-impact resin was used.
      Tooth surface modification by grinding or grooving made no significant difference
      when compared with unmodified surfaces. Wax-contaminated surfaces produced highly
      significant weaker bonds. Time of introduction and duration of water-bath
      processing had no significant effect on bond strength. Monomer cementing of the
      tooth surface, especially with high-impact monomer. significantly improved the
      bond strength. The application of resin cements was found to produce the most
      significant increase in denture tooth bond strength. CONCLUSIONS: The important
      steps in obtaining a consistently high value denture tooth bond are thorough
      dewaxing of the tooth surface followed by the application of a suitable resin
      cement.

PMID- 10071471
TI  - Surface fine structure of treated dentine investigated with tapping mode atomic
      force microscopy (TMAFM).
AB  - OBJECTIVES: The objective of this study was to investigate the surface morphology
      and roughness of human dentine treated with different dentine conditioning agents
      with tapping mode atomic force microscopy (TMAFM). METHODS: Dentine samples from
      third permanent molar teeth were prepared as flat disks. The samples were treated
      with different conditioning agents for 15-30 s: aqueous phosphoric acid and those
      supplied with three commercial adhesive products. The surface morphology and
      roughness was measured with tapping mode atomic force microscopy, a highly
      resolving method which minimises unwanted side effects of conventional AFM.
      RESULTS: The tubules, the areas between the tubules and the entire surface showed
      variations in surface morphology and roughness, depending on the conditioning
      agent used. These differences might affect the bonding properties of the agents
      in dentine/polymer systems. CONCLUSIONS: The surface structure, such as the
      tubules diameters and depths, the local height differences of the surface between
      the tubules and the overall mean surface roughness Ra varies between samples
      treated with different conditioning agents. All conditioning agents, however, led
      to exposed and open tubules. CLINICAL RELEVANCE: The direct observation of
      effects of conditioning agents on dentine is important in order to judge their
      performance under clinically relevant conditions-free of desiccation artefacts. A
      vast number of conditioning agents is available today. The differences in their
      actual effects on dentine surfaces, however, are less than clear to many users.

PMID- 10071472
TI  - Colour perception of laboratory-fired samples of body-coloured ceramic.
AB  - The objective of this investigation is to test by common perception, the colour
      fidelity of laboratory-fired samples of ceramic. Thirty-two ceramic discs were
      constructed in a thickness similar to that used for ceramic veneers using eight
      shades from each of four different manufacturers. A group of 20 'adept' observers
      colour matched the samples in strictly controlled viewing conditions using a Vita
      Lumin (Vita Zahnfabrik) shade guide. Samples were categorised as 'positive
      matches'(matching the expected shade), 'agreed shades' (matching an unexpected
      shade), or as 'unidentified shades' (no match). The Vita Lumin (Vita Zahnfabrik)
      colour 'value' index was used as a reference to categorise colour 'value'
      differences between observed and expected shade. Colour 'value' selection was
      divided into three groups: (1) matching colour 'value', (2) shades of higher
      colour 'value' than expected or (3) shades of lower colour 'value' than expected.
      Only six of the 32 samples examined were perceived to be 'positive matches' with
      the recommended shade guide. Fourteen 'agreed shades' were found while the
      remaining 12 shades were regarded as 'unidentified shades'. The vast majority of
      observations disagreed with the manufacturers' designated shade. A significant
      trend was found favouring higher 'value' (lighter) shades than those specified by
      the manufactures. Significant differences in the pattern of shade matches and
      disagreements between brands were also found. Alternative shade determination
      systems and/or ceramic colour modifications are required if colour fidelity
      between the shade guide and the materials tested is to be improved.

PMID- 10071473
TI  - Influence of light irradiation on the volumetric change of polyacid-modified
      resin composites.
AB  - OBJECTIVES: Recently, a new restorative material called a 'compomer', which is
      classified as a polyacid-modified resin composite, has become available. The
      volumetric shrinkage of compomers may create marginal gaps that influence the
      bonding ability and longevity of a restoration. Since compomers have been
      introduced recently, their volumetric change during curing is not fully
      understood. The purpose of this study was to evaluate the volumetric change of
      compomers. METHODS: Three compomers, Compoglass (Vivadent), Dyract (Dentsply),
      and Ionosit Fil (DMG) were employed. The material was placed into a Teflon mould,
      4 mm in diameter and 2 mm height, and extruded into the dilatometer. Then the
      specimens were light activated and the change in the height of the meniscus of
      water was recorded using a CCD camera and VRC. RESULTS: The average volumetric
      shrinkages of the compomers after 160 s were 2.4% for Compoglass, 2.7% for
      Dyract, and 2.1% for Ionosit-Fil. For all materials tested, there was a tendency
      of increasing volumetric shrinkage with increased irradiation time. CONCLUSIONS:
      The results of this study indicate that the volumetric change of compomer is
      influenced by the duration of light exposure, light intensity, and environmental
      conditions to which the materials are exposed.

PMID- 10071474
TI  - The influence of alloy copper content on the polymerisation of anaerobic
      adhesives.
AB  - OBJECTIVES: Anaerobic adhesives are capable of bonding copper-containing metal
      attachments to etched human enamel, where the latter surface has been rendered
      reactive by the use of a copper-containing surface activator. The aims of the
      present study were to determine whether copper attachments could also be
      successfully bonded to etched human enamel, using anaerobic adhesives, where no
      such surface activator was used. In addition, the effect of alteration in the
      copper content of the attachment alloy was also investigated. METHODS: Metal
      attachments suitable for use with anaerobic adhesives were made from one of three
      copper-containing alloys. Their copper contents were 8%, 19% and 99.9%. They were
      bonded to human enamel, which had been ground flat and etched with 37% o
      phosphoric acid, using one of three anaerobic adhesives. After bench curing for
      one of four time periods, 10 min, 1 h, 24 h and 2 weeks, shear testing to failure
      was performed. The load at debond was recorded in each case. RESULTS: The results
      were analysed using mean force to debond (N) and 95% confidence intervals. Kaplan
      Meier survival probabilities and log-rank tests were performed for the 10 min and
      1 h test times. CONCLUSIONS: Each of the three anaerobic adhesives under test
      demonstrated a concentration effect for the copper in the metal attachments. The
      higher the copper content of the attachment the greater the measured force to
      debond and the more rapid its attainment. As determined by measured force to
      debond, only one adhesive. Loctite 326, underwent any significant degree of
      activation and, therefore, polymerisation by the lowest copper content alloy
      under test.

PMID- 10071475
TI  - In-vitro study of fracture strength and marginal adaptation of fibre-reinforced
      adhesive fixed partial inlay dentures.
AB  - The aim of this study was to examine in-vitro whether adhesive fixed posterior
      inlay dentures (AFPID) made with the fibreglass-reinforced Vectris/Targis system
      (Ivoclar, Schaan, FL) have a fracture strength and a satisfactory marginal
      adaptation which can occur under clinical conditions. Extracted human third
      molars were embedded in a PMMA resin 10 mm apart to represent a molar gap. Two
      preparation methods were used: a box-shaped preparation technique (n = 8) and a
      tub-shaped preparation technique (n = 8). All AFPIDs were adhesively inserted
      using the dual curing composite cement, Variolink-high-viscosity (Vivadent,
      Schaan, FL). After thermocycling and mechanical loading (TCML: 6000 x 5 degrees
      C/55 degrees C, 1.2 Mio x 50 N, 1.66 Hz) in an artificial environment, the
      bridges were loaded to failure. Marginal adaption was investigated before and
      after TCML with the replica technique. After TCML, no significant difference was
      found in fracture strength between tub-shaped-preparation (median = 722 N,
      bending median = 0.9 mm) and box-shaped preparation (median = 696 N, bending
      median = 1.2 mm). A 'perfect margin' was observed in more than 60% of the
      investigated areas in both preparation techniques. With these values, the bridges
      can occur under clinical conditions and thus a clinical employment should be
      considered.

PMID- 10071476
TI  - The J.I.M. interview. Kenneth I. Shine, MD.

PMID- 10071477
TI  - How should quality of life be measured?

PMID- 10071478
TI  - The physician-scientist: a new generation or the last?

PMID- 10071479
TI  - High density lipoproteins in health and in disease.

PMID- 10071480
TI  - L-arginine stimulates NO-dependent vasodilation in healthy humans--effect of
      somatostatin pretreatment.
AB  - BACKGROUND: L-arginine is the precursor of endogenous nitric oxide (NO) and a
      potent stimulator of pituitary growth hormone and pancreatic insulin secretion.
      Both hormones have vasodilatory effects, which may be mediated via NO. We
      investigated whether growth hormone and/or insulin secretion contributes to L
      arginine-induced vasodilation. METHODS: Ten healthy male subjects received an
      intravenous infusion of L-arginine, or L-arginine during somatostatin coinfusion
      lasting 30 minutes. Blood pressure, heart rates, and total peripheral resistance
      were assessed from 30 minutes prior to L-arginine infusion to 120 minutes after
      the start of the infusion. Plasma nitrite and cGMP concentrations were used as
      markers for endogenous NO formation. RESULTS: L-arginine significantly reduced
      total peripheral resistance, which remained decreased for 60 minutes after the
      end of the infusion. This resulted in a significantly lowered blood pressure. L
      arginine elevated plasma nitrite and cGMP concentrations. Plasma growth hormone
      level showed a peak at 30 minutes after the infusion, while insulin and glucagon
      levels were maximal during the infusion, these endocrine effects were blocked
      during somatostatin coinfusion. The initial reduction in total peripheral
      resistance and blood pressure, and the elevation of nitrite and cGMP levels were
      still present during somatostatin cotreatment, but values returned to baseline
      more rapidly at the end of the L-arginine infusion. CONCLUSION: We conclude that
      growth hormone contributes to the late phase of L-arginine-induced, NO-mediated
      vasodilation. By contrast, insulin did not mediate L-arginine induced
      vasodilation, as the early vasodilator effect, which occurred concomitantly with
      the peak insulin secretion, was still present after insulin secretion was blocked
      with somatostatin.

PMID- 10071481
TI  - Age-related decrease in accessory cell function of human alveolar macrophages.
AB  - BACKGROUND: Suboptimal function of an aged immune system may significantly
      contribute to morbidity and mortality in the elderly. In contrast to lymphocytes,
      only little is known about changes of cells from the monocyte/macrophage lineage.
      Especially the changes of their accessory function, which are necessary for
      optimal T cell stimulation are controversially discussed. METHODS: We measured
      the accessory function of monocytes (PBM) and alveolar macrophages (AM) and
      correlated their accessory function with the age of the patients. RESULTS: We
      found a significant decrease in accessory function of AM with the age (rs = -0.5,
      P < 0.006) but not of PBM (rs = -0.4, P > 0.1). Additionally, we found a
      significant decrease in the percentage of AM (rs = 0.3, P < 0.005) and an
      increase in the percentage of lymphocytes (rs = 0.3, P < 0.02) in the
      bronchoalveolar lavage. No correlations could be found with other lavage
      parameters or with unstimulated in vitro TNF-alpha, TGF-beta, and IL-6 release of
      bronchoalveolar lavage cells; however, in stimulated BAL-cell cultures we found a
      weak but significant correlation between TNF-alpha release and the age (rs = 
      0.3, P < 0.02). CONCLUSIONS: Impairment of accessory cell function of alveolar
      macrophages may contribute to an increased risk of pulmonary infection of elderly
      persons.

PMID- 10071482
TI  - Meloxicam effect on leukocyte migration under shear stress: a new perfused triple
      chamber (Hofbauer chamber) assay simulating an in vitro vascular wall.
AB  - BACKGROUND: Leukocyte migration plays a tremendous role during inflammation.
      Different drugs are able to influence migration of leukocytes. Several authors
      have attempted to establish methods for investigation of leukocyte migration.
      Migration of leukocytes under conditions simulating natural blood flow and shear
      stress is poorly understood. Moreover, leukocyte migration in the simultaneous
      presence of endothelial cells and smooth muscle cells (SMC) has not yet been
      examined thoroughly. The aim of the current study was to create a new three
      dimensional assay investigating migration during simulated perfusion. The assay
      was used for investigating the effect of meloxicam on leukocyte migration under
      shear stress. METHODS: Different concentrations of meloxicam (0.09, 0.9, and 9.0
      ng/mL) were used in a newly developed triple migration chamber system for
      investigation of leukocyte migration (n = 7). This new system allows inclusion of
      SMC-layers. Assay precision tests were done using intra-assay (within-day
      variability) and interassay (day-to-day variability) controls. RESULTS: Intra
      assay and interassay controls showed reliable results (coefficient of variation:
      intra-assay 8.53%; interassay 11.39%). Meloxicam in a clinically relevant
      concentration of 0.9 ng/mL was able to reduce the migration of leukocytes under
      shear stress (71 +/- 14% SD; P < 0.05), whereas higher and lower concentrations
      showed a dose dependent effect. CONCLUSION: This new perfusion system allows
      investigation of drugs, such as meloxicam, on leukocyte migration under shear
      stress. Moreover, this assay may be used for studies on other cell-cell
      interactions, as well as on drug influences.

PMID- 10071483
TI  - Expression of monocyte chemotactic protein-1 precedes monocyte recruitment in a
      rat model of acute liver injury, and is modulated by vitamin E.
AB  - BACKGROUND: Increased expression of monocyte chemotactic protein-1 (MCP-1) has
      been indicated as a mechanism underlying leukocyte recruitment after liver
      injury. In this study we examined the temporal relationship between MCP-1
      expression and the appearance of monocyte infiltration during acute liver injury.
      In addition, we tested the effects of vitamin E, a well known antioxidant, on
      these parameters. Rats were intoxicated with a single intragastric administration
      of CCl4 with or without pretreatment with vitamin E (atocopherol). METHODS:
      Monocyte chemotactic protein-1 expression was analyzed by northern blotting and
      in situ hybridization and monocyte infiltration was determined by ED-1
      immunostaining. The results were quantitated by computerized image analysis.
      Expression of MCP-1 mRNA was significantly increased as early as 12 hours
      following injury, and progressively increased thereafter. In contrast, a
      significant increase in the number of ED-1 positive cells, an index of monocyte
      infiltration, was observed only 24 and 48 hours after injury. RESULTS: Vitamin E
      markedly reduced MCP-1 expression at the mRNA and protein levels, and caused a
      significant reduction in the number of monocyte/macrophages, indicating a role
      for oxidative stress in the induction of MCP-1 expression in vivo. Accordingly,
      in cultured hepatic stellate cells, different oxidative stress-related molecules
      increased MCP-1 mRNA. CONCLUSIONS: These data suggest the existence of a direct
      relationship between MCP-1 expression and monocyte infiltration after acute liver
      injury, and that preventing the generation of oxidative stress-related molecules
      results in decreased expression and release of this chemokine.

PMID- 10071484
TI  - Coagulation protein function: the influence of acetaldehyde-modified heparin on
      thrombin activity.
AB  - BACKGROUND: The affect of acetaldehyde-treated heparin on thrombin activity has
      been investigated using factor II-deficient human plasma. METHODS: It was
      observed that 0.021 units of heparin exerts a marked inhibition of thrombin
      activity (1.03 units) as measured by clotting times, prolonging the clotting
      times from 9.6 +/- 0.1 seconds to 24.8 +/- 0.1 seconds. However, when the heparin
      is preincubated with 447 mmol/L acetaldehyde at RT for 30 minutes prior to mixing
      with thrombin, a clotting time in excess of 200 seconds is observed. Clotting
      times remain elevated with heparin-acetaldehyde mixtures of 89.4, 17.9, 3.6, and
      0.72 mmol/L acetaldehyde, with corresponding clotting times of > 200, 156.0 +/-
      2.1, 81.6 +/- 1.0, 38.8 +/- 0.6 seconds, respectively. At 140 mumol/L
      acetaldehyde-heparin mixtures, the clotting time was 17.0 +/- 2.0 seconds.
      RESULTS: These data support the hypothesis from this laboratory that acetaldehyde
      modified heparin enhances coagulation time. They further indicate that thrombin
      is targeted by the acetaldehyde-treated heparin. Heparin-acetaldehyde mixtures
      also reacted with plasma prior to the addition of thrombin to modestly prolong
      coagulation time. Similarly, but more effectively, thrombin/heparin mixtures
      increased the clotting time of acetaldehyde-exposed plasma. These data further
      suggest the possibility that reactions of acetaldehyde and heparin are not
      restricted to those with thrombin, and that they may extend to other blood
      factors/proteins. CONCLUSIONS: The amount of heparin (0.021 units) required to
      substantially affect clotting time of thrombin (1.03 units) is substantially
      lower than that required to prolong clotting of 0.1 mL of whole plasma (0.36
      units), by an order of magnitude. It is inferred that heparin may interact with
      numerous cationic proteins or proteins with cationic domains in blood plasma,
      among them being the clotting factors.

PMID- 10071485
TI  - 1995 epizootic of vesicular stomatitis (New Jersey serotype) in the western
      United States: an entomologic perspective.
AB  - Entomologic and epizootic data are reviewed concerning the potential for
      transmission of vesicular stomatitis (VS) virus by insects, including field data
      from case-positive premises in New Mexico and Colorado during the 1995 outbreak
      of the New Jersey serotype (VSNJ). As with previous outbreaks of VSNJ in the
      western United States, the 1995 epizootic illustrated that risk of exposure is
      seasonal, increasing during warm weather and decreasing with onset of cool
      weather; virus activity spread from south to north along river valleys of the
      southwestern and Rocky Mountain states; clinical disease was detected most
      commonly in horses, but also occurred in cattle and 1 llama; and most infections
      were subclinical. Overall, 367 case-positive premises were identified during the
      1995 outbreak, with foci of virus activity along the Rio Grande River south of
      Albuquerque, NM, in southwestern Colorado, and along the Colorado River near
      Grand Junction, CO. The establishment of a 16-km (10-mile) radius zone of
      restricted animal movement around confirmed positive premises, along with
      imposition of state and international embargoes, created economic hardship for
      livestock owners and producers. The importance of defining the role of blood
      feeding insects as biological vectors of VSNJ virus relative to risk factors that
      promote high levels of insect transmission, such as the presence of livestock
      along western river valleys, blood feeding activity, and frequent transport of
      animals for recreational purposes, is emphasized as a basis for developing
      effective disease management.

PMID- 10071486
TI  - Amounts of glycogen, lipid, and sugar in adult female Aedes aegypti (Diptera:
      Culicidae) fed sucrose.
AB  - We examined the amount of glycogen, lipid, and sugar in small and large female
      Ae. aegypti (L.) that were fed different concentrations of sucrose. Replicate
      groups of laboratory-reared teneral females (< or = 1 d old) were allowed to feed
      ad libidum on a 0, 5, 10, 15, or 20% sucrose solution, and total glycogen,
      lipids, and sugars were assayed at 4, 12, 24, 48, and 72 h after exposure to
      sugar. Mosquitoes fed sugar increased nutrient levels with time. The pattern of
      accumulation was significantly different between small and large mosquitoes.
      Large mosquitoes accumulated larger amounts of glycogen than small ones.
      Accumulation of lipid increased sooner in small (4 h) than large (48 h) Ae.
      aegypti. A significant size x time interaction for the amount of sugar per female
      indicated that small mosquitoes may need to feed more than once during a 72-h
      period to compensate for low energy reserves at emergence. We conclude that the
      pattern of energy utilization from sugar meals by Ae. aegypti is influenced by
      the amount of energy reserves that they have before feeding and not by the
      concentration of sugar on which they feed.

PMID- 10071487
TI  - Utilization of human blood and sugar as nutrients by female Aedes aegypti
      (Diptera: Culicidae).
AB  - We examined the utilization of sugar and human blood as nutrient sources for
      small and large female Aedes aegypti (L.) when they were fed blood 2 or 5 d after
      emergence. Laboratory-reared mosquitoes were fed human blood alone or sugar plus
      human blood and assayed at 4, 12, 24, and 48 h after the blood meal. Starved and
      well-fed mosquitoes were obtained by holding teneral females (< or = 1 d old)
      with 0, 5, 10, and 15% sucrose solutions ad libidum from emergence. Both small
      and large mosquitoes increased their glycogen and sugar levels significantly by
      feeding on blood only or on blood plus sugar when they imbibed a human blood meal
      on day 2 after emergence. Mosquitoes only fed blood on day 2 had the highest
      lipid levels of any treatment group. Both size classes and all feeding regimes
      failed to increase the total amount of glycogen, lipid, or sugar when they fed on
      blood 5 d after emergence. We conclude that there is an energetic advantage to
      Ae. aegypti when they feed on blood early in adult life (< or = day 2 after
      emergence).

PMID- 10071488
TI  - Partitioning of glycogen, lipid, and sugar in ovaries and body remnants of female
      Aedes aegypti (Diptera: Culicidae) fed human blood.
AB  - We examined the accumulation of glycogen, lipid, and sugar obtained from a human
      blood meal for egg development and body energy reserves by small and large female
      Aedes aegypti (L.). Small and large mosquitoes were fed a single meal of human
      blood on day 2 after emergence. Mosquitoes were collected at 4, 12, 24, 48, and
      72 h after blood feeding and ovaries and body remnants were separated by
      dissection and then assayed. Large mosquitoes had greater reserves than small
      mosquitoes. Mosquitoes deposited similar proportions of lipid reserves obtained
      from blood meals in their ovaries regardless of body size. Small mosquitoes
      deposited a significantly higher proportion of their glycogen in ovaries than
      large mosquitoes. The pattern of energy accumulation and use indicates that to
      avoid starvation, mosquitoes fed a single human blood meal will need to feed
      again before ovipositing, and that multiple feeding may be more important for
      small than for large Ae. aegypti.

PMID- 10071489
TI  - Temporal and spatial genetic variation within and among populations of the
      mosquito Culex tarsalis (Diptera: Culicidae) from California.
AB  - The genetic structure of 11 populations of Culex tarsalis Coquillett from
      California and 1 population from Nevada was examined at 18 loci using
      polyacrylamide gel electrophoresis. Six populations from northern and southern
      California were sampled repeatedly to determine if the genetic structure of Cx.
      tarsalis changes seasonally. Significant differences in allele frequencies at 13
      different loci were seen in 3 populations over time as determined by contingency
      chi-square tests. Nei's genetic distance coefficients among different sampling
      dates was consistently < 0.025. The number of alleles per locus in these
      populations ranged from 1.6 to 2.7, whereas the average heterozygosity ranged
      from 0.086 to 0.228. No single locus was found to vary in a consistent pattern
      within all populations that were sampled repeatedly. These results indicate that
      Cx. tarsalis populations are genetically stable over time and that temporal
      variation is due to fluctuations in population size or immigration of genetically
      distinct individuals. In contrast, Cx. tarsalis did exhibit some differences in
      genetic structure that were related to geographical features including the Sierra
      Nevada and the Tehachapi Mountains of southern California. Genetically
      differentiated populations occurred in Nevada, southern and northeastern
      California, and the Central Valley of California. Little differentiation was
      observed among populations located in the Central Valley of California and those
      located at high elevations in the Sierra Nevada. Thus, in the populations
      examined, mountain ranges or arid conditions that limit the number of larval
      development sites appeared to be important barriers to the dispersal of Cx.
      tarsalis.

PMID- 10071490
TI  - Dispersal, survivorship, and host selection of Culex erythrothorax (Diptera:
      Culicidae) associated with a constructed wetland in southern California.
AB  - Three mark-recapture studies were carried out at a constructed wetlands facility
      in San Jacinto, CA, to examine the dispersal and population ecology of the most
      abundant host-seeking mosquito, Culex erythrothorax Dyar, collected in carbon
      dioxide-baited traps. Recapture rates were 0.3, 7.4, and 13.9% for August,
      September, and October, respectively. The mean distance traveled per night was
      approximately 0.5 km, and females were not recaptured farther than 2 km from the
      release site. Most marked individuals (> or = 99.5%) were recaptured within 0.5
      km of the release point. Marked individuals were recaptured for 33 d after
      release. Horizontal estimates of survival calculated using recapture data were
      0.89, 0.87, and 0.84/d for August, September, and October, respectively. Temporal
      differences in the recapture rate were attributed to the effects of blood meal
      acquisition on host-seeking activity versus effects of mortality and strong
      developmental site fidelity on weekly recapture rates. Partially engorged females
      collected by CO2-baited traps at the wetland fed predominantly on cattle
      indicating that host-seeking females were using hosts at dairies surrounding the
      wetland and were returning to the wetland for resting before seeking an
      additional blood meal. Estimates of the gonotrophic cycle length and survivorship
      (vertical estimates) were problematical because of the low parity rates for
      females collected by CO2-baited traps. Limited dispersal and long survival of Cx.
      erythrothorax are important factors in the development of large populations at
      constructed wetlands.

PMID- 10071491
TI  - Interruption of chemical mosquito control and evolution of insecticide resistance
      genes in Culex pipiens (Diptera: Culicidae).
AB  - Within the Llobregat Delta (Barcelona, Spain), Culex pipiens L. has been the
      target of organophosphate insecticide (OP) control for 10 yr (1982-1992). Between
      1991 and 1992, OPs were replaced by Bacillus-based toxins in all the mosquito
      control programs within > 150 km of this area. The distribution of several OP
      resistance genes was surveyed within the Llobregat Delta and neighboring
      populations (< 25 km) during the 2 yr following this regional pesticide change to
      investigate how the change in selection pressure affected the dynamics of OP
      resistance genes. The immigration failure of the A2-B2 resistant esterases and
      the observed difference in OP-resistance dynamics between isolated and
      nonisolated populations may indicate fitness disadvantages associated with OP
      resistance genes, hence a tendency for a decrease in OP-resistance. In contrast,
      one OP-resistance gene further increased in frequency, whereas the frequencies of
      some others were maintained. These unexpected results question the importance of
      pesticides from sources other than mosquito control, and the variability of
      pleiotropic fitness costs among pesticide resistance genes.

PMID- 10071492
TI  - Presence of sex pheromones in Anocentor nitens (Acari: Ixodidae).
AB  - The aim of this study was to investigate whether there are sex pheromones in the
      tropical horse tick, Anocentor nitens (Neumann). When virgin males and females,
      fed on rabbits for 3-7 d, were tested reciprocally, there was a direct
      correlation between attractiveness and the period of feeding; attraction was
      greater (and with the fastest responses) in males and females fed for at least 6
      d (sexually active males and confirmed attractive females). The capacity of
      sexually active males to orient topward confirmed attractive females decreased as
      the emission distance increased; the maximum distance that evoked a response by
      males was 6 cm. Confirmed attractive females lost their attractiveness
      approximately 2 h after being separated from the host, or after being killed by
      ethanol injection, although some females continued to attract sexually active
      males up to 4 h after death. An extract was produced by immersing confirmed
      attractive females in hexane and submitting them to ultrasound. Sexually active
      males were more attracted to and spent more time on glass bead dummies treated
      with this extract when compared with those treated with the hexane alone. Our
      results indicate the presence of at least 2 sex pheromones (attractant and
      mounting) in attractive females of A. nitens.

PMID- 10071493
TI  - Effect of nutrient levels and Ascogregarina taiwanensis (Apicomplexa:
      Lecudinidae) infections on the vector competence of Aedes albopictus (Diptera:
      Culicidae) for Dirofilaria immitis (Filarioidea: Onchocercidae).
AB  - The effect of habitat nutrients and Ascogregarina taiwanensis (Lein & Levine)
      infection on the vector competence of a New Orleans strain of Aedes albopictus
      (Skuse) for Dirofilaria immitis (Leidy) were evaluated. Larvae were infected with
      A. taiwanensis oocysts and reared under high and deficient nutrient conditions
      using leaf litter as a food source. Ascogregarine-infected and uninfected females
      were fed on D. immitis-infected blood and examined after 15 d for filariae.
      Susceptibility to infection with filaria was 60-70% for all females. In groups
      reared under high nutrients, the infective rate (3rd-stage larvae present) of
      coinfected females (18%) was significantly greater than females infected only
      with heartworm (6%). Host mortality following blood meals was significantly less
      in coinfected (22%) than in heartworm-infected females (37%). Under deficient
      nutrient conditions, there was no significant difference between the infective
      rate (8%) or post-blood meal mortality (5%) of coinfected females compared with
      heartworm-infected females. Prevalence of melanization reactions in coinfected
      females was significantly higher (31%) than in females infected only with
      heartworm (6%) at both nutrient levels. It is concluded that high nutrient levels
      and ascogregarine infection increase the vector competence of Ae. albopictus for
      D. immitis by enhancing the immune response so that fewer filariae develop,
      causing lower host mortality. Under low nutrient conditions, the smaller host
      contains less food reserves for filariae development, and in coinfected females
      melanization reactions and damage to the Malpighian tubules may reduce vector
      survival.

PMID- 10071494
TI  - Experimental formulations of Bacillus sphaericus and B. thuringiensis israelensis
      against Culex quinquefasciatus and Anopheles gambiae (Diptera: Culicidae) in
      Burkina Faso.
AB  - Efficacies of locally produced, sustained release granular formulations of
      Bacillus sphaericus (BS) strain 2362 and B. thuringiensis israelensis (BTI) were
      compared with commercial liquid concentrates of the same bacteria in cesspits and
      rain-filled puddles in Ouagadougou, Burkina Faso. Duration of control was
      dependent on the product, the transient nature of some sites, and the target
      mosquito larvae. BS granules applied at the rate of 3.0 g/m2 (30 kg/ha) reduced
      Culex quinquefasciatus Say 99% for at least 28 d in cesspits, whereas the same
      dosage of 2 BTI granules and commercial liquid formulations of BS and BTI gave
      95% control for 8-14 d. The levels of control obtained with the 2 liquid products
      were not different. Accordingly, the reported inferiority of BTI to BS in
      polluted water was attributed to low dosages of BTI. Because products were
      compared at equal application rates, recycling seemed to play a minor role
      compared with product formulation. BTI was more broad spectrumed than BS also
      killing Cx decens Theobald, Cx cinereus Granpre & Charmoy, and psychodid larvae.
      Depending on the method of estimation, granular and liquid BS gave 60-97% control
      of Anopheles gambiae s.l. Giles for 10 d in rain puddles. The transient nature of
      the rain puddles was probably more important for the duration of control than
      formulation type. Cesspits and puddles, respectively, were the most important
      larval habitats for these 2 species in Ouagadougou during the rainy season, and
      these trials showed that An. gambiae was not controlled easily with larvicides
      alone. However, biological larvicides may play a central role in the control of
      Cx. quinquefasciatus provided that most breeding sites are treated.

PMID- 10071495
TI  - Effects of temperature and humidity on oviposition, molting, and longevity of
      Dermanyssus gallinae (Acari: Dermanyssidae).
AB  - The juvenile development and survival of Dermanyssus gallinae (De Geer) kept in
      vitro at different temperatures and humidity were investigated to obtain
      biological baseline data for a Swedish population. Individual females, eggs,
      larvae, and protonymphs were observed with regard to egg production, duration of
      various stages, and longevity when kept at different temperatures and relative
      humidities. Female mites laid eggs at temperatures between 5 and 45 degrees C
      with the highest numbers laid at 20 degrees C and 70% RH, but development to
      larvae and protonymphs was only observed at temperatures ranging from 20 to 25
      degrees C. The average duration of oviposition varied from 1.0 to 3.2 d within
      the temperature range 20-45 degrees C but was gradually increased to 28 d at 5
      degrees C. Specimens survived for up to 9 mo without access to food when kept in
      the temperature range of 5-25 degrees C. Temperatures > 45 degrees C and at -20
      degrees C were found to be lethal. Longevity was similar for females and
      protonymphs kept at 30 and 45% RH, but it was enhanced at 70 and 90% RH for
      protonymphs. This study showed that D. gallinae can survive for a long time
      without feeding if the microclimate is suitable, but it does not thrive at low
      relative humidities and at temperature extremes. This indicates that changing of
      the abiotic conditions in infested poultry houses could be a possible measure to
      reduce mite populations.

PMID- 10071496
TI  - Mortality of horn fly larvae (Diptera: Muscidae) in bovine dung supplemented with
      ergotamine and N-formyl loline.
AB  - Dung-dwelling larvae of ectoparasites of livestock such as the horn fly,
      Hematobia irritans (L.), may be exposed to > or = 1 different alkaloid species in
      dung from animals ingesting herbage of the tall fescue (Festuca arundinacea
      Schreb.)--endophyte association (Neotyphodium coenophialum (Morgan-Jones & W.
      Gams) Glenn, Bacon & Hanlin comb. nov.). First-instar horn flies were exposed to
      bovine dung supplemented with up to 50 microM each of N-formyl loline and
      ergotamine tartrate in factorial combination. In the absence of ergotamine
      tartrate, N-formyl loline caused a linear decline in the number of pupae
      recovered, and probit analysis indicated an LC50 of 36 microM. In the absence of
      N-formyl loline, significant quadratic responses of larvae to ergotamine tartrate
      were established, and probit analysis indicated a LC50 of 34 microM. An
      interaction (P < 0.001) was found between the 2 alkaloids for larval survival.
      This interaction showed that ergotamine tartrate moderated the toxicity of N
      formyl loline and indicates that a membrane-bound receptor may be involved. There
      was no evidence of carryover of effects of alkaloids on subsequent stages of
      development or expressed as abnormalities of pupae or adults. Interactions
      between alkaloids probably are involved in other plant-herbivore relationships of
      endophyte-infected grasses.

PMID- 10071497
TI  - Description and morphometric analysis of the eggs of Anopheles (Anopheles)
      vestitipennis (Diptera: Culcidae) from southern Mexico.
AB  - Light and scanning electron microscopy were used to compare the eggs of Anopheles
      vestitipennis Dyar & Knab females collected from human and animal baits in 9
      villages of southern Mexico. An. vestitipennis eggs are boat-shaped, with lateral
      floats extending the length of the egg. Both the deck and dorsal surface are
      covered with hexagonal and pentagonal chorionic cells that contain round
      tubercles in the cell field. Crowns that enclose 3-5 lobed tubercles are present
      at both egg poles. By light microscopy, the mean length/width ratio of eggs of
      females caught at human bait were statistically different from those of females
      caught in horse-baited animal traps. In a regression tree model that included 19
      egg attributes, the same egg groups could be separated by their posterior crown
      length/width ratio and mean anterior cell deck form factor (an index of their
      roundness). These findings support of the possible existence of 2 An.
      vestitipennis subpopulations with different host preferences in southern Mexico.

PMID- 10071498
TI  - Redescription of Leptotrombidium (Leptotrombidium) imphalum (Acari:
      Trombiculidae), with observations on bionomics and medical importance in northern
      Thailand.
AB  - Leptotrombidium (Leptotrombidium) imphalum Vercammen-Grandjean & Langston is
      redescribed and illustrated. Specimens were collected from the rodents Rattus
      rattus, Rattus losea, and Bandicota indica in Chiangrai Province, northern
      Thailand. The species was found on hosts collected on dikes at the margins of
      rice fields and in adjacent fruit plantations and along irrigation canals,
      especially in areas covered with the grasses Imperata cylindrica (lalang grass)
      and Saccharum arudinaceum. The etiological agent of scrub typhus, Orientia
      (formerly Rickettsia) tsutsugamushi has been isolated from L. (L.) imphalum,
      rodent hosts, and patients who live and work in the same habitats.

PMID- 10071499
TI  - Effect of lufenuron on chorionic and cuticular structure of unhatched larval
      Ctenocephalides felis (Siphonaptera: Pulicidae).
AB  - When adult cat fleas, Ctenocephalides felis (Bouche), were fed concentrations of
      < or = 0.08 ppm lufenuron in cattle blood, egg hatch did not differ significantly
      from the controls. However, as the concentration of lufenuron in blood increased
      from 0.125 to 1.0 ppm egg hatch decreased to 64 and 2%, respectively. Most of
      these eggs contained fully developed larvae. Microscopic examination of unhatched
      larvae, revealed that the cuticle epidermal cells, chorion, and vitelline
      membrane all were affected by lufenuron treatment. Larvae often produced 2
      separate cuticles in response to treatment. The 1st cuticle consisted of an
      indistinct layer of epicuticle and a procuticle composed of randomly deposited
      chitin microfibrils. After the 1st layer of procuticle separated from the
      epidermal cells, a 2nd layer of procuticle was deposited. It was not possible to
      determine whether the egg tooth was functional during larval hatch. The surface
      of the egg tooth appeared normal, but the cuticle may have had structural
      abnormalities similar to those seen in other areas of the exoskeleton. Structural
      defects appeared to be due to the cytotoxic effects of lufenuron. The epidermal
      cells of treated larvae showed evidence of disintegration (i.e., the nuclei and
      mitochondria appeared to be degenerating and the amount of endoplasmic reticulum
      and other cytoplasmic organelles was decreased). The chorion of lufenuron-treated
      larvae consisted of an outer layer, middle and inner layers that were thinner and
      less electron dense than those of controls, and lacked the innermost chorionic
      layer found in the control larvae. The vitelline membrane also was thinner than
      that of the controls. Larval hatching was prevented by ruptures in the cuticle,
      which opened during eclosion resulting in the loss of hemolymph and desiccation
      of the larva. Evidently, tearing of the cuticle was caused by abnormal formation
      of the procuticle that was not strong enough to withstand the cuticular expansion
      and muscular movement of the larva within the egg shell.

PMID- 10071500
TI  - Differences in energy metabolism and adult desiccation resistance among three
      Aedes (Stegomyia) species (Diptera: Culicidae) from South Sulawesi, Indonesia.
AB  - To determine the mechanisms of adult desiccation resistance of Aedes (Stegomyia)
      species, we estimated the carbohydrate and lipid contents of newly emerged adult
      mosquitoes from South Sulawesi, Indonesia. Inter- and intraspecific differences
      in glycogen and free fatty acid accumulation were found in Aedes aegypti (L.),
      Ae. albopictus (Skuse), and Ae. paullusi (Stone & Farmer). High glycogen content
      was determined for both sexes in all Ae. aegypti strains and in the Ujung Pandang
      strain of Ae. albopictus. There were no differences among species in either
      trehalose or sorbitol content. A trend similar to glycogen was seen for lipid
      content, especially the free fatty acids of neutral lipids. These energy reserves
      of adult mosquitoes correlated with adult desiccation survival time at 90% RH
      calculated by Mogi et al. (1996). In both sexes, survival time was longer in
      strains with high glycogen and free fatty acid content, and low trehalose
      content. Ae aegypti, Ae. albopictus, and Ae. paullusi are species with high,
      intermediate, and low levels of glycogen and free fatty acids, respectively.
      However, longevity of these species under desiccation conditions is associated
      strongly with glycogen-trehalose conversion, and free fatty acid accumulation.

PMID- 10071501
TI  - Detection of Escherichia coli O157:H7 from Musca domestica (Diptera: Muscidae) at
      a cattle farm in Japan.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 was isolated for the first time
      from Musca domestica L. A total of 310 fly samples was collected from 4 different
      farms in Obihiro-City, Hokkaido, in the summer and autumn of 1997;5 samples
      carried E. coli serotype O157:H7. Using ELISA and Vero cell cytotoxicity assay, 3
      isolates from 1 cattle farm produced both active Shiga-toxin type 1 (Stx1) and 2
      (Stx2). These isolates also carried hemolysin and eaeA genes and harbored the 90
      kb virulence plasmid of EHEC O157:H7. Based on plasmid profiles, antibiotic
      patterns, polymerase chain reaction (PCR)-based DNA finger printing analysis
      using random amplified polymorphic DNA, pulsed field gel electrophoresis
      analysis, and DNA sequences of stx1 and stx2, all 3 isolates from fly samples
      were identical. These results indicate that the house fly is capable of carrying
      the toxigenic EHEC O157:H7 involved in human disease.

PMID- 10071502
TI  - Mosquito repellent attracts Culicoides imicola (Diptera: Ceratopogonidae).
AB  - A plant-derived mosquito repellent, based on the oil of Eucalyptus maculata var.
      citriodora Hook, was evaluated against the biting midge Culicoides imicola
      Kieffer. Suction black light-traps covered with repellent-impregnated polyester
      mesh and deployed near horses attracted large numbers of C. imicola, which were
      seen near the treated net within a few minutes of the start of the experiment.
      Initial collections in the traps were approximately 3 times as large as those in
      control traps with untreated mesh. Numbers collected in treated traps were
      similar to untreated control traps after 4 h. Traps with mesh treated with DEET
      or another plant-derived (Meliaceae) proprietary product, AG1000, acted as
      repellents relative to the control. The differential activity of repellents
      against blood-feeding Diptera is discussed.

PMID- 10071503
TI  - Morphological and isoenzymatic differentiation of sympatric populations of
      Phlebotomus perniciosus and Phlebotomus longicuspis (Diptera: Psychodidae) in
      northern Morocco.
AB  - The phlebotomine sandfly Phlebotomus perniciosus Newstead is a vector of
      Leishmania infantum Nicolle in the western Mediterranean basin. In northern
      Morocco it is often caught in sympatry with a closely related species, P.
      longicuspis Nitzulescu. In the locality of Chefchaouene where females of both
      species were morphologically distinguishable, none of the collected males
      exhibited forked copulatory valves, which is considered a specific character for
      P. perniciosus. They 1st were identified as P. longicuspis. Isoelectrofocusing of
      7 enzyme systems was used to compare these specimens with the sympatric females.
      Two groups of males were separated and assigned to each species by their
      isoenzyme patterns associated with morphological differences in the shape of the
      aedeagus and in the number of coxite hairs. Based on our results, a reexamination
      of the distribution of both species is necessary especially in many locations
      where P. longicuspis has been identified only from males.

PMID- 10071504
TI  - Flotation method for extracting insects from poultry manure samples.
AB  - We examined the efficacy of a sucrose-based flotation method for extracting 3
      prevalent insect species from poultry house manure: 3rd-instar Musca domestica L.
      (Diptera: Muscidae), Carcinops pumilio (Erichson) (Coleoptera: Histeridae)
      adults, and Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) adults. A
      0.6 M sucrose solution in distilled water altered the specific gravity to 1.2 and
      caused the 3 species to float to the water surface for easy separation. An
      analysis of variance (ANOVA) showed significant effects of the solution volume to
      sample mass ratio on recovery rates (F = 35.96, P < 0.0001), but no differences
      in species-specific recovery rates (F = 0.97, P = 0.3824). Among samples agitated
      in a ratio of at least 3.2 ml solution per gram of sample mass, we observed
      neither significant ratio effects (F = 1.37, P = 0.2442) nor significant
      differences in species-specific recovery rates (F = 2.05, P = 0.1353); overall,
      we recovered 97.49 +/- 0.20% of all individuals of the 3 species. Our analyses
      demonstrated that sucrose-based flotation was a statistically valid method of
      collecting these species from poultry manure samples.

PMID- 10071505
TI  - [Uric acid as a scavenger in oxidative stress].
AB  - Uric acid, the naturally occurring product of purine metabolism, is widely used
      as a diagnostic parameter in different diseases. The concentration of uric acid
      may vary between broad ranges without causing symptoms, like idiopathic
      hyperuricemia, which behind metabolic disorders were always suggested. Recently
      the uric acid has been shown as a strong scavenger of oxidative stress molecules
      or radicals. Uric acid was successfully used to treat experimental allergic
      encephalomyelitis, the mouse model of multiple sclerosis (M. S.). It was shown,
      that patients with multiple sclerosis had significantly lower levels of serum
      uric acid than the control persons. In addition, statistical evaluation of more
      than 20 million patient records for the incidence of MS and hyperuricemic gout
      revealed, that the hyperuricemia may protect against MS.

PMID- 10071506
TI  - [Measure of bone loss in rheumatoid arthritis].
AB  - The authors examined the degree of bone loss by single photon osteodensitometry
      in 72 patients with rheumatoid arthritis (RA). A control group was set up
      consisting of osteoarthritis patients of the same age and gender. As a result of
      the osteodensitometrical examination osteopenia was observed in 22-, osteoporosis
      in 37- and normal density in 14 rheumatoid arthritis patients. These results
      showed considerable difference compared to the density results of the control
      group (n = 72) (p < 0.001). They also analysed the role of risk factors affecting
      bone loss in three groups of rheumatoid arthritis patients, with osteoporosis,
      osteopenia and with normal density results. As risk factors the duration of the
      rheumatoid arthritis, the duration of the postmenopause, the age, the cumulative
      doses of steroid and the activity of rheumatoid arthritis were mentioned. Among
      risk factors the duration of the rheumatoid arthritis, the age, the duration of
      the postmenopause and the Steinbrocker phase classification correlated with the
      osteodensitometrical results. At the same time no correlation has been observed
      in relation to the cumulative doses of steroid and the Ritchie joint index.

PMID- 10071507
TI  - [Surgical treatment of mitral insufficiency using annuloplasty suture technic].
AB  - In 1991 a simple and cheap technique was introduced for mitral valve repair at
      our department. After repairing the mitral leaflets, where indicated a posterior
      leaflet annuloplasty was performed with a semicircular suture and the annulus
      fixed for the appropriate size by tying the stitch. Between July 1991 and
      December 1995 86 patients underwent the above procedure (average age 56.8 +/-
      10.4 years). 45 patients had primary mitral valve disease (myxomatous
      degeneration, rheumatoid disease, endocarditis), the other 41 had functional
      mitral regurgitation secondary to severe aortic valve or coronary artery disease.
      Echocardiography showed severe mitral regurgitation in 77% of the patients. In 45
      cases the mitral valve itself was also repaired (valvotomy, quadrangular
      resection, wedge resection, etc.) in 29 cases the aortic valve was replaced as
      well, while 24 patients required additional revascularisation of the myocardium.
      The 30 day mortality was 3.5%. One week after surgery echocardiography was
      performed at all patients and showed acceptable mitral valve area (2.28 +/- 0.39
      cm2). In 28 cases mild mitral regurgitation was found, the other valves were
      competent. All but 3 patients were followed up (96.4%). There were 6 late deaths
      (3 cardiac, 2 non cardiac, 1 embolic, 7.2% late mortality). During the follow up
      period (31.7 +/- 11.2 months) 5 patients required mitral valve replacement for
      severe recurrent mitral regurgitation (6.0%). In two cases new chorda rupture
      caused the recurrence, in an other case the suture had torn out of the annulus
      due to inadequate surgical technique. In the last two cases the annulus had
      dilated with intact Prolene annuloplasty stitch present, 86.8% of the survivors
      were in NYHA class I. or II. Our results suggest that mitral valve repair in
      selected cases can be performed without using expensive annuloplasty rings. The
      suture used for annuloplasty should be strong, non absorbable and non
      stretchable. Since 1994, when we started using GoreTex suture instead of Prolene
      no more patients required reoperation for annuloplasty failure.

PMID- 10071508
TI  - [Gastric MALT lymphoma, clinical features].
AB  - Gastric mucosa associated lymphoma (MALT) can be regarded as a pathogenetic
      continuum of reactive B lymphocyte accumulation due to Helicobacter pylori
      infection, which after a series of mutation may presumably transform into a low
      grade and later on into a high grade MALT lymphoma. If the lymphoma is confined
      to the mucosa or strictly to the superficial part of gastric wall, a
      conventional, regular Helicobacter pylori eradication procedure has a good chance
      to bring about clinical, histological and less frequently molecular biological
      remission as well.

PMID- 10071509
TI  - [A Hungarian physician from the past century: Mor Herczegy (1815-1884)].

PMID- 10071510
TI  - [Brief history of mammography in Hungary and its development until the present
      day].

PMID- 10071511
TI  - Bayesian predictive identification and cumulative classification of bacteria.
AB  - In this paper we give a mathematically precise formulation of an old idea in
      bacterial taxonomy, namely cumulative classification, where the taxonomy is
      continuously updated and possibly augmented as new strains are identified. Our
      formulation is based on Bayesian predictive probability distributions. The
      criterion for founding a new taxon is given a firm theoretical foundation based
      on prediction and it is given a clear-cut interpretation. We formulate an
      algorithm for cumulative classification and apply it to a large database of
      bacteria belonging to the family Enterobacteriaceae. The resulting taxonomy makes
      microbiological sense.

PMID- 10071512
TI  - A mathematical model for simulating virus transport through synthetic barriers.
AB  - Synthetic barriers such as gloves, condoms and masks are widely used in efforts
      to prevent disease transmission. Due to manufacturing defects, tears arising
      during use, or material porosity, there is inevitably a risk associated with use
      of these barriers. An understanding of virus transport through the relevant
      passageways would be valuable in quantifying the risk. However, experimental
      investigations involving such passageways are difficult to perform, owing to the
      small dimensions involved. This paper presents a mathematical model for analyzing
      and predicting virus transport through barriers. The model incorporates a
      mathematical description of the mechanisms of virus transport, which include
      carrier-fluid flow, Brownian motion, and attraction or repulsion via virus
      barrier interaction forces. The critical element of the model is the empirically
      determined rate constant characterizing the interaction force between the virus
      and the barrier. Once the model has been calibrated through specification of the
      rate constant, it can predict virus concentration under a wide variety of
      conditions. The experiments used to calibrate the model are described, and the
      rate constants are given for four bacterial viruses interacting with a latex
      membrane in saline. Rate constants were also determined for different carrier
      fluid salinities, and the salt concentration was found to have a pronounced
      effect. Validation experiments employing laser-drilled pores in condoms were also
      performed to test the calibrated model. Model predictions of amount of
      transmitted virus through the drilled holes agreed well with measured values.
      Calculations using determined rate constants show that the model can help
      identify situations where barrier-integrity tests could significantly
      underestimate the risk associated with barrier use.

PMID- 10071513
TI  - Parkinsonian tremor and simplification in network dynamics.
AB  - We explore the behavior of richly connected inhibitory neural networks under
      parameter changes that correspond to weakening of synaptic efficacies between
      network units, and show that transitions from irregular to periodic dynamics are
      common in such systems. The weakening of these connections leads to a reduction
      in the number of units that effectively drive the dynamics and thus to simpler
      behavior. We hypothesize that the multiple interconnecting loops of the brain's
      motor circuitry, which involve many inhibitory connections, exhibit such
      transitions. Normal physiological tremor is irregular while other forms of tremor
      show more regular oscillations. Tremor in Parkinson's disease, for example, stems
      from weakened synaptic efficacies of dopaminergic neurons in the nigro-striatal
      pathway, as in our general model. The multiplicity of structures involved in the
      production of symptoms in Parkinson's disease and the reversibility of symptoms
      by pharmacological and surgical manipulation of connection parameters suggest
      that such a neural network model is appropriate. Furthermore, fixed points that
      can occur in the network models are suggestive of akinesia in Parkinson's
      disease. This model is consistent with the view that normal physiological systems
      can be regulated by robust and richly connected feedback networks with complex
      dynamics, and that loss of complexity in the feedback structure due to disease
      leads to more orderly behavior.

PMID- 10071514
TI  - Reciprocal effects of age and clinical allergy: is there more to be learned?

PMID- 10071515
TI  - Mannose-binding lectin (MBL) deficiency. Variant alleles in a midwestern
      population of the United States.
AB  - OBJECTIVES: To describe a method for the genotype analysis of mutations in the
      gene encoding mannose binding lectin (MBL), study the incidence of MBL gene
      mutations in a population of the Midwest of the United States, and compare it
      with previous reports in other populations. The objective of this report is also
      an extensive review of the literature to analyze the importance of MBL deficiency
      in human disease. DATA SOURCES: Blood samples were obtained from the blood bank
      of the Mayo Clinic. They represented a population of blood donors living in the
      Midwest of the United States. A review of the literature was performed by
      selection of articles from Medline database. STUDY SELECTION: Blood samples, 148,
      were randomly selected from a pool of blood donors. They included both females
      and males. Blood donors had been previously screened by a questionnaire and were
      found to be generally healthy. For the literature review, articles containing
      original data on MBL in humans were selected. RESULTS: Forty-five (30.4%) of the
      analyzed blood donors carried one variant allele, while 8 donors (5.4%) showed
      homozygosity or compound heterozygosity for MBL gene mutations. Allele frequency
      for the different MBL variants is provided. Our results are similar to those
      reported for the Danish population. Literature review provides evidence for a
      significant role of MBL deficiency in the innate immunity. The incidence of MBL
      mutations is higher among patients with recurrent infections and autoimmune
      disorders. CONCLUSIONS: Mannose binding lectin deficiency has a definite role in
      the pathogenesis of primary immunodeficiency in humans and screening patients
      with recurrent infections and autoimmunity might be beneficial. The significance
      of MBL deficiency among apparently healthy blood donors remains to be determined.

PMID- 10071516
TI  - A patient with persistent wheezing, sinusitis, elevated IgE, and eosinophilia.

PMID- 10071517
TI  - Changes in skin and nasal sensitivity to allergens and the course of rhinitis; a
      long-term follow-up study.
AB  - BACKGROUND: Allergic skin test reactivity tends to decrease with aging, but
      whether the decrease is associated with changes in symptom severity and duration
      of the disease or determined only by aging, is poorly understood. OBJECTIVE: Our
      aim was to analyze skin test sensitivity some 20 years after primary testing and
      to relate possible changes in reactivity to aging, duration of rhinitis, and
      changes in severity of rhinitis symptoms. METHODS: One hundred and seven rhinitis
      patients who had been investigated earlier were re-interviewed and their current
      allergy re-assessed after a follow-up of 23 years. All patients were skin prick
      tested with 22 to 26 common allergens. The allergic rhinitis status was verified
      with nasal allergen challenge. RESULTS: Skin test reactivity showed a significant
      trend decreasing towards older age groups over the period between the two
      investigations. Rhinitis symptoms tended, on average, to become milder during the
      follow-up, but an association between skin test reactivity and changes in symptom
      severity could not be verified. CONCLUSIONS: Rhinitis symptoms tend to become
      milder and the allergic skin reactivity usually decreases in the long run, but
      these changes may occur independently of each other. In this study, the change in
      rhinitis symptom severity seems not to be related to the decrease in skin test
      reactivity.

PMID- 10071518
TI  - Central nervous system effects of H1-receptor antagonists in the elderly.
AB  - BACKGROUND: The potential adverse central nervous system effects of H1-receptor
      antagonists have not been optimally studied in the elderly. OBJECTIVE: We
      hypothesized that newer H1-receptor antagonists such as cetirizine and loratadine
      would cause less central nervous system dysfunction than the older H1-receptor
      antagonists diphenhydramine and chlorpheniramine in this population, as they do
      in younger subjects. METHODS: We performed a randomized, double-blind, single
      dose, placebo-controlled, 5-way crossover study in 15 healthy elderly subjects
      (mean age 71 +/- SD 5 years). On study days at least 1 week apart, they received
      cetirizine 10 mg, loratadine 10 mg, diphenhydramine 50 mg, chlorpheniramine 8 mg,
      or placebo. Outcome measures, recorded before and 2 to 2.5 hours after dosing
      were latency of the P300 event-related potential in which increased latency
      reflects a decreased rate of cognitive processing, visual analogue scale for
      subjective somnolence, and histamine skin tests for measurement of peripheral H1
      blockade. RESULTS: The changes in P300 following each treatment yielded variances
      that were not equal (P > .05), precluding usual statistical analysis of the
      means. These variances were ranked: chlorpheniramine > diphenhydramine >
      loratadine > placebo > cetirizine. The rank of mean differences in the visual
      analogue scale increase from pre-dose baseline was: diphenhydramine >
      chlorpheniramine > cetirizine > loratadine > placebo. All H1-receptor antagonists
      suppressed the histamine-induced wheal and flare significantly compared to
      baseline. CONCLUSION: In the elderly, the new H1-receptor antagonists cetirizine
      and loratadine are less likely to cause adverse central nervous system effects
      than the old H1-antagonists chlorpheniramine or diphenhydramine, but this
      requires confirmation using additional objective tests of central nervous system
      function.

PMID- 10071519
TI  - Comparison of exhaled nitric oxide to spirometry during emergency treatment of
      asthma exacerbations with glucocorticoids in children.
AB  - BACKGROUND: Asthma is characterized as a chronic inflammatory process; however,
      there is no easily measured marker for airway inflammation. Such a marker,
      particularly in children, would be very helpful in the management of asthma even
      in the acute setting. OBJECTIVE: The purposes of this study were to determine
      whether asthmatic children have (1) elevation of exhaled breath nitric oxide
      (ENO) during acute exacerbations when presenting to the emergency room, (2)
      reduction of ENO following glucocorticoid treatment, or (3) improvement in
      spirometry and clinical examination accompanying reduction of ENO levels.
      METHODS: Peak ENO levels were measured by chemiluminescence during exhalation
      into the NO analyzer. Ten asthmatic children (mean age 10 years) who presented to
      the Pediatric Special Care Unit at National Jewish Medical and Research Center in
      acute respiratory distress with an asthma exacerbation were studied. The subjects
      were recruited, after informed consent was obtained from the parent, on the basis
      of specific inclusion/exclusion criteria. Measurements of ENO in parts per
      billion (ppb) and spirometry, including percentiles of forced expiratory volume
      in one second (FEV1%) and peak expiratory flow (PEF%), were performed before and
      after at least 5 days of glucocorticoid therapy. RESULTS: The mean ENO level in
      the asthmatic children prior to glucocorticoid treatment was 48 +/- 8ppb, and
      after glucocorticoid treatment the ENO level was 17 +/- 1ppb; (P < .002). Prior
      to glucocorticoid treatment, the mean FEV1% value was 68 +/- 3% compared with the
      postglucocorticoid treatment FEV1% value of 100 +/- 5%; (P < .0001). Prior to
      glucocorticoid treatment, the mean PEF% value was 81 +/- 7%, compared with the
      postglucocorticoid treatment PEF% value of 105 +/- 6%; (P < .02). CONCLUSIONS:
      The mean peak ENO level after glucocorticoid therapy was significantly less than
      that measured before treatment in children with acute asthma exacerbations.
      Concomitant with the decrease in ENO levels, there was improvement in the
      spirometry values and physical examination in the asthmatic children; thus, ENO
      is a sensitive marker for response to anti-inflammatory treatment in children.

PMID- 10071520
TI  - Factors predisposing infants to lower respiratory infection with wheezing in the
      first two years of life.
AB  - BACKGROUND: Acute lower respiratory illness (LRI) early in life has been
      implicated as a factor for adverse respiratory outcomes later in life. Factors
      that predispose infants to LRI with wheezing have not been conclusively defined.
      OBJECTIVES: This prospective study assessed factors that might contribute to LRI
      with wheezing in the first 2 years of life. METHODS: Seventy-one healthy full
      term infants (44 boys, 27 girls) completed the 2-year follow-up. Demographic and
      environmental factors were evaluated by questionnaire. Respiratory function was
      assessed by single occlusion technique and rapid thoracic compression technique.
      Both techniques were performed successfully in 40 infants at 2.6 (+/- 1.4) months
      old before they developed any episode of LRI. RESULTS: Eighteen infants (25%)
      developed LRI with wheezing. The first episode of LRI with wheezing occurred in
      the first year of life in 8 infants, and in the second year of life in 10
      infants. There were no significant differences in the demographic or
      environmental features between infants with or without wheezing LRI, or between
      infants who acquired LRI with wheezing in the second year of life and those who
      did not acquire or acquired in the first year of life. Infants from different
      groups did not differ in airway resistance or maximal flow at functional residual
      capacity. Infants who developed LRI with wheezing had higher incidence of low
      values for total respiratory system compliance corrected for body weight compared
      with those who did not (5/30 versus 6/10, odds ratio = 7.5, 95% confidence
      interval: 1.53 to 36.7, P = .013). None of the variables of the pulmonary
      function test could differentiate infants who subsequently developed LRI with
      wheezing in the first year of life or did not develop any episode of LRI with
      wheezing from those who developed LRI with wheezing in the second year of life.
      CONCLUSIONS: Differences in lung function in early life may predispose infants to
      LRI with wheezing in the first 2 years of life.

PMID- 10071521
TI  - Occupational asthma and IgE sensitization to cellulase in a textile industry
      worker.
AB  - BACKGROUND: Although there have been a few reports of occupational asthma due to
      cellulase in several occupational settings, this is the first case of cellulase
      induced occupational asthma in an employee working in the textile industry. Its
      pathogenetic mechanism remains to be further clarified. OBJECTIVE: It is
      important to alert physicians to the possibility of occupational asthma caused by
      cellulase in workers of the textile industry. METHODS AND RESULTS: The patient
      had atopy and strong positive responses to cellulase extract on skin prick tests.
      Bronchoprovocation test showed an early asthmatic response to cellulase extract.
      Serum specific IgE and specific IgG4 antibodies to cellulase were detected by
      enzyme-linked immunosorbent assay (ELISA). In order to further characterize the
      allergenic component of the extract, sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and electroblotting studies were performed. Eight IgE
      binding components ranging from 6 to 97.5 kD were detected within the cellulase
      extract. CONCLUSION: These findings suggest that inhalation of cellulase can
      induce IgE-mediated bronchoconstrictions in employees working in the textile
      industry.

PMID- 10071522
TI  - In vitro responses to antigen stimulation: comparison between human lung
      parenchyma resected from asthmatic patients and non-asthmatic patients.
AB  - BACKGROUND: The airway of asthmatic patients is hyperresponsive to various
      stimuli in vivo. There are, however, only a few reports that compared the in vivo
      responsiveness of asthmatic patients and non-asthmatic subjects to those of lung
      parenchyma in vitro. OBJECTIVES: To compare the contractile response, release of
      various chemical mediators, and responsiveness to drugs in samples of lung
      parenchyma excised from asthma patients with those of non-asthmatic subjects.
      METHODS: Human lung parenchymal strips were subjected to passive sensitization
      with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath
      containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha.
      After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene
      (LT), and histamine were measured in each bath and then contraction was induced
      by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine
      were measured after contraction. The inhibitory effects of TXA2 synthetase
      inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in
      both tissue samples. RESULTS: There were no significant differences between lung
      parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2
      alpha-induced contraction, antigen-induced contraction, release of chemical
      mediators, and the response to drugs. CONCLUSION: Unlike the response in vivo,
      there are no differences in the response to stimuli in vitro between lung
      parenchymal tissues of asthmatic and non-asthmatic patients.

PMID- 10071523
TI  - Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue
      syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology,
      consisting of prolonged, debilitating fatigue, and a multitude of symptoms
      including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness,
      arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and
      swelling and tenderness of lymph nodes. No effective treatment for CFS is known.
      OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced
      form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral
      absorbable form, in a randomized, double-blind, placebo-controlled crossover
      study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger
      energy production through ATP generation which may form the basis of its
      potential effects. METHODS: Twenty-six eligible patients who fulfilled the Center
      for Disease Control and Prevention criteria for CFS completed the study. Medical
      history, physical examination, laboratory studies, and questionnaire were
      obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to
      receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week
      washout period, subjects were crossed to the alternate regimen for a final 4-week
      period. RESULTS: No severe adverse effects were observed related to the study
      drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to
      NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results
      we have decided to conduct an open-label study in a larger cohort of patients.
      CONCLUSION: Collectively, the results of this pilot study indicate that NADH may
      be a valuable adjunctive therapy in the management of the chronic fatigue
      syndrome and suggest that further clinical trials be performed to establish its
      efficacy in this clinically perplexing disorder.

PMID- 10071524
TI  - Tobacco allergy: demonstration of cross-reactivity with other members of
      Solanaceae family and mugwort pollen.
AB  - BACKGROUND: Tobacco is a plant belonging to the Solanaceae family. This plant is
      usually used as a contact insecticide for several infestations in some areas,
      such as the Canary Islands. Allergy induced by inhalation of this plant is
      unusual. Identification of the potential allergen in growing areas is essential.
      OBJECTIVE: We report a patient with occupational sensitivity to an aqueous
      solution of cut tobacco whose clinical manifestations were rhinoconjunctivitis
      and urticaria. Past medical history was significant for seasonal allergic
      rhinoconjunctivitis to mugwort pollen and oral allergy syndrome with avocado.
      METHODS: Green tobacco and cured tobacco leaf extracts were prepared, skin prick
      tests were performed with green tobacco, cured tobacco leaf extracts, and certain
      aeroallergens. Conjunctival challenge test was carried out with green tobacco and
      cured tobacco leaf extract. Serum-specific IgE against tobacco leaf was performed
      by commercial CAP. CAP inhibition experiments were carried out with tobacco and
      Artemisia vulgaris. RESULTS: Skin prick tests and conjunctival challenge tests
      with green tobacco and cured tobacco leaf extracts were positive, as well as
      serum-specific IgE by CAP, indicating an IgE-mediated sensitization. CAP
      inhibition experiments were carried out and it was found that tobacco, mugwort
      pollen, and tomato extracts inhibited the binding of the patient's serum to solid
      phase tobacco leaf. No inhibition was observed when Alternaria, D. pteronyssinus,
      and potato were used as control inhibitors. Inhibition of immunoCAP to mugwort
      was obtained with mugwort and tobacco extracts and no cross-reactivity to D.
      pteronyssinus was shown. CONCLUSION: The results suggest that tobacco can induce
      IgE-mediated reactions that are mediated by the existence of common antigenic
      epitopes between tobacco and mugwort pollen. This allergy can be a hazard of
      employment in the agricultural areas.

PMID- 10071525
TI  - Linkage of house dust mite allergy with the HLA region.
AB  - BACKGROUND: Atopy is a multifactorial disease, the pathogenesis of which is
      influenced by both genetic and environmental conditions. Genes in the HLA region
      have been involved in the control of the IgE response. OBJECTIVE: In order to
      investigate whether allergy to house dust mite is associated with HLA in our
      population, we performed sib-pair analysis in 18 families and a case/control
      study of 161 non-related individuals. METHODS: Levels of total and specific IgE
      were determined, skin-prick tests were carried out and clinical history was
      reviewed for every subject in the study. HLA class II typing was performed by the
      polymerase chain reaction with sequence specific primers. RESULTS: We observed a
      significant difference from expected values in haplotypes shared by affected
      sibs; however, the case/control study did not reveal any association with any
      particular allele. CONCLUSION: These results suggest that any particular HLA
      DRB1/DQA1/DQB1 allele is responsible for the development of allergy to house dust
      mite in the Spanish population. Some other locus in or close to the HLA region
      might be involved, e.g., the tumour necrosis factor gene, a possibility that
      would explain the significant difference from expected values in the segregation
      of HLA haplotypes.

PMID- 10071526
TI  - Prevention of exercise-induced bronchospasm in pediatric asthma patients: a
      comparison of salmeterol powder with albuterol.
AB  - BACKGROUND: Exercise-induced bronchospasm (EIB) is a common problem in children
      with asthma. Pretreatment with the beta2 (beta 2)-adrenoreceptor agonist
      albuterol is effective for preventing EIB, but is recognized as providing only
      short-term (2 to 3 hour) protection. OBJECTIVE: To evaluate the 12-hour efficacy
      and safety of single doses of 25 micrograms and 50 micrograms of salmeterol
      powder administered via Diskus inhaler versus albuterol aerosol via pressurized
      metered-dose inhaler and placebo in preventing EIB in asthmatic children.
      METHODS: A randomized, double-blind, placebo-controlled, double-dummy, single
      dose, four-way crossover study was conducted in pediatric patients (4 to 11 years
      of age) demonstrating EIB and mild-to-moderate asthma. Serial forced expiratory
      volume in 1 second (FEV1) was measured before and after standard treadmill
      exercise at hour 1, hour 6, and hour 12 after administration of 25 micrograms or
      50 micrograms salmeterol powder, 180 micrograms albuterol aerosol, or placebo.
      Adverse events were recorded. RESULTS: After completion of the hour 1 exercise
      challenge, mean minimum % predicted FEV1 was significantly higher following
      albuterol (91.3%) than for placebo (75.3%) and for both dosages of salmeterol
      (86.9% and 85.8% for salmeterol 25 micrograms and 50 micrograms, respectively; P
      < or = .026). After completion of both the hour 6 and hour 12 exercise
      challenges, the 50-microgram salmeterol treatment produced a significantly higher
      mean minimum percent of predicted FEV1 (90.6% and 87.3% predicted, respectively)
      than the mean minimum percent of predicted FEV1 for placebo or albuterol (73.8%
      to 78.4% of predicted; P < or = .041). At hour 6, the 25-microgram salmeterol
      treatment was not significantly different from albuterol or placebo. At hour 12,
      the 25-microgram salmeterol treatment mean minimum percent of predicted was
      significantly higher than albuterol (87.9% versus 73.8% of predicted; P = .006)
      and there was also a trend toward significance over placebo (76.9% predicted; P =
      .056). At all exercise periods, no statistically significant differences in
      spirometry values were observed between the two salmeterol treatment groups.
      Safety profiles were similar among treatments, including placebo. No drug-related
      adverse events or withdrawals due to adverse events occurred. Changes in
      laboratory values, vital signs, 12-lead ECGs, and physical examinations were
      unremarkable. CONCLUSIONS: A single 50-microgram dose of salmeterol powder
      provided effective and safe protection against EIB for at least 12 hours in
      asthmatic children and provided a significantly more prolonged effect than
      albuterol aerosol (180 micrograms).

PMID- 10071527
TI  - Interleukin-6 synthesis and IgE overproduction in children with perinatal human
      immunodeficiency virus-type 1 infection.
AB  - BACKGROUND: Unbalanced interleukin network and elevated IL-6 synthesis are
      suggested mechanisms of immunoglobulin overproduction in children with perinatal
      human immunodeficiency virus-type 1 (HIV-1) infection. OBJECTIVE: To investigate
      whether elevated IL-6 synthesis is a general mechanism of immunoglobulin
      overproduction in perinatal HIV-1 infection. METHODS: In vitro spontaneous and
      phytohaemoagglutinin (PHA)-stimulated IL-6 and IL-2 synthesis, serum IgE, IgG,
      IgA, and IgM levels, CD4+ T-lymphocyte counts, and HIV-1 RNA copy numbers were
      cross-sectionally determined in 31 children with perinatal HIV-1 infection.
      Children with immunoglobulin z-scores in the highest quartile were defined as
      children with high immunoglobulin level. Relationships between interleukin
      synthesis, high immunoglobulin levels, and HIV-1 related disease were studied.
      RESULTS: Children with high IgE levels had higher spontaneous IL-6 synthesis
      (1337 +/- 138 pg/mL) compared with those without high IgE levels (861 +/- 194
      pg/mL; P < .001). By contrast, spontaneous IL-6 synthesis was similar in children
      with or without high IgG, IgA, or IgM levels. Decreased PHA-stimulated IL-2
      synthesis, low CD4+ lymphocyte counts, elevated HIV-1 RNA copy numbers, and
      severe disease correlated with high IgE (but not IgG, IgA, and IgM) levels. IgG,
      IgA, and IgM levels correlated with each other, but not with IgE levels.
      CONCLUSION: The increased IL-6 synthesis in HIV-1+ children may affect IgE rather
      than other immunoglobulin isotype levels. Overall results suggest that IgE and
      IgG, IgA, IgM overproduction have distinct underlying mechanisms.

PMID- 10071528
TI  - Differential regulation of human blood monocyte and alveolar macrophage
      inflammatory cytokine production by nitric oxide.
AB  - BACKGROUND: Nitric oxide (NO) has been associated with airway inflammation in
      asthma. Our previous work suggests that NO functions in an anti-inflammatory
      capacity through downregulation of stimulated cytokine secretion by normal human
      alveolar macrophages. Functional differences between alveolar macrophages and
      blood monocytes are thought to be related to maturation. OBJECTIVE: The purpose
      of this study was to determine the effect of NO on stimulated cytokine production
      by monocytes from asthmatics and normal healthy controls. METHODS: Monocytes and
      alveolar macrophages were obtained from normal volunteers (n = 13) and asthmatics
      with atopy (n = 7). Monocyte and alveolar macrophage cultures were stimulated
      with 0.5 microgram/mL lipopolysaccharide +/- 1.0 mM DETA NONOate (releases NO in
      culture with t1/2 = 20 hours at 37 degrees C) and incubated for 24 hours. Cell
      free supernatants were collected and assayed by ELISA for tumor necrosis factor
      alpha (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF).
      RESULTS: Nitric oxide did not inhibit TNF production in monocytes of asthmatics
      and normals (mean +/- SEM % TNF stimulation = 19.6 +/- 9.7). Similar to previous
      results, NO did inhibit alveolar macrophages (% TNF suppression = 60.6 +/- 4.4).
      To determine whether this differential effect of NO on the two cell populations
      was related to maturation, monocytes were matured by culture for 7 days. The in
      vitro matured monocytes demonstrated 51.7 +/- 7.9% suppression of TNF. For each
      cell population, the responses of the asthmatics and healthy controls were not
      different. The differential effect is not cytokine specific since similar results
      were obtained with GM-CSF. CONCLUSION: These results demonstrate a differential
      effect of NO on monocyte and alveolar macrophages cytokine regulation and this
      effect may be related to the state of maturation.

PMID- 10071530
TI  - Urodynamics and the International Continence Society come of age.

PMID- 10071529
TI  - New occupational allergen in citrus farmers: citrus red mite (Panonychus citri).
AB  - BACKGROUND: There have been several reports of occupational allergy to spider
      mites (Tetranychidae), but no published report has described citrus red mite
      (CRM, Panonychus citri)-induced occupational asthma confirmed by specific
      bronchial challenge. OBJECTIVE: The purpose of this study was to evaluate
      clinical and immunologic characteristics of CRM-induced occupational asthma.
      METHODS AND RESULTS: We encountered 16 cases of CRM-induced occupational asthma
      among farmers cultivating citrus fruits. Asthmatic attacks corresponded closely
      with their work on citrus farms. The mean duration of the latent period was 12.9
      (range 7 to 20) years. During their first visit to our clinic, nine patients with
      FEV1 lower than 70% of predictive value showed reversible airway obstruction
      after inhalation of bronchodilator, and seven with FEV1 greater than 70% of
      predictive value showed airway hyperresponsiveness to methacholine. Fifteen of
      the 16 also complained of recurrent nasal symptoms, which had developed at an
      earlier time than the asthmatic symptoms. They showed strong positive reactions
      to CRM extract on skin prick test (A/H ratio > or = 1.0) and had high serum
      specific IgE antibody against CRM which was detected by ELISA. Skin prick test
      with common inhalant allergens revealed that 10 had an isolated positive response
      to CRM with negative results to common inhalant allergens in their environment.
      The ELISA inhibition tests with CRM demonstrated significant inhibitions by CRM
      in a dose-dependent manner, while minimal inhibitions were noted by D.
      pteronyssinus and mugwort allergens. CONCLUSION: These findings suggest that CRM
      could induce IgE-mediated bronchoconstriction in exposed workers on citrus farm.

PMID- 10071531
TI  - Extracorporeal shock wave lithotripsy in patients with renal malformations.
AB  - Twenty-four consecutive patients with malformed kidneys (21 horseshoe kidneys, 2
      crossed ectopic and 1 pelvic kidney) underwent extracorporeal shock wave
      lithotripsy (ESWL) for nephrolithiasis between 1984 and 1990. No serious
      complications occurred either during or after treatment. Urinary obstruction was
      accompanied by fever in 3 patients and by renal colic in 4. Auxiliary measures
      were required in only 2 cases. Patients with renal anomalies remained in hospital
      longer than patients with normal kidneys. Fifteen patients were free of stones 3
      months after ESWL and 16 after 1 year. Six patients required further ESWL less
      than 1 year after their first treatment as a result of stone recurrence or
      regrowth. ESWL is a safe and successful non-invasive procedure for the treatment
      of nephrolithiasis in patients with malformed kidneys. However, the higher
      frequency of stone recurrence and regrowth means that these patients must undergo
      careful monitoring.

PMID- 10071532
TI  - Responses of renal function to elevated intravesical pressure.
AB  - This experimental study was designed to investigate the responses of renal
      function to elevated intravesical pressure. Ten male New Zealand type rabbits
      were used. A supravesical ureterocutaneous urinary diversion was performed in all
      rabbits to disconnect bladder and kidneys and to ensure a free urine flow. Two
      parameters of renal function were measured simultaneously: urine output by simple
      collection and glomerular filtration rate (GFR) by total plasma clearance of 51Cr
      EDTA. Measurements were performed initially with the bladder empty and then with
      intravesical pressure 60 cm H2O. A significant decrease in urine output and in
      GFR was observed in all rabbits when the bladder was overdistended. Urine output
      returned to the initial levels after relief of the increased intravesical
      pressure. The results suggest that for these responses a vesicorenal reflex
      activated by the elevated intravesical pressure is responsible.

PMID- 10071533
TI  - In vitro analysis of urinary calculi: type differentiation using computed
      tomography and bone densitometry.
AB  - Thirty-six urinary stones were studied by computed tomography and bone
      densitometry in order to find a correlation between the chemical composition of
      the stones and the densitometric data. In vitro, the more common cases of
      lithiasis can be divided into 3 main groups: uric acid, cystine and the calcium
      salts, e.g. calcium oxalate monohydrate, calcium oxalate dihydrate and calcium
      phosphate. Struvite stones fall between the second and third groups. Computed
      tomography and bone densitometry can differentiate between the groups, provided
      that the value of the "stone mineral or calcium content" is correlated with the
      true calculated volume of the stone (resulting in the specific stone density)
      instead of the projection area (resulting in the area density). This is only
      possible in vitro. The in vivo application of these technologies in the treatment
      of stones of unknown composition could provide important information, but major
      restrictive factors pose difficulties. Further clinical studies are necessary,
      especially to define the role of bone densitometry.

PMID- 10071534
TI  - Bacterial factors in the formation of renal scars. An experimental study on the
      role of Escherichia coli P-fimbriation and hydrophobicity.
AB  - A model capable of comparing the effects of bacterial virulence factors on renal
      scarring in vivo has been developed using the female piglet. By creating, at open
      surgery, unilateral vesicoureteric reflux (VUR) and quantifying scarring both by
      uptake of an isotope bound to functioning renal parenchyma and by planimetry of
      the surface area scarred, the effects of 2 organisms, a P-fimbriate Escherichia
      coli and an E. coli K1 have been compared. The P-fimbriate E. coli was shown to
      express P-fimbriae in freshly voided urine, was more hydrophobic and produced
      smaller scars. This indicates that neither the hydrophobicity nor P-fimbriation
      of the organism causing urinary tract infection (UTI) is of prime importance for
      the development of renal scars and is evidence against the "big bang" theory for
      the development of renal scars. Studies on the association of UTI with VUR showed
      that infection with both E. coli under study led to VUR on the side contralateral
      to the side undergoing surgery. It seems likely that a non-specific effect of
      UTI, such as bladder oedema, is responsible for this acquired VUR. An effect of
      the 2 bacteria under study on the lower urinary tract was observed in that
      infection with the P-fimbriate E. coli allowed the retention of an intravesical
      wax plug, whereas infection with E. coli K1 did not. Epidemiological data have
      shown that the majority of upper urinary tract infections in children are
      associated with UTI by P-fimbriate organisms. Such an association may be
      explained in part by an effect of P-fimbriate bacteria on lower urinary tract
      function rather than an effect on the upper urinary tract.

PMID- 10071535
TI  - Reconsideration of the roles of urinary infection and vesicoureteric reflux in
      the pathogenesis of renal scarring.
AB  - In an experimental study of female piglets with surgically created unilateral
      vesicoureteric reflux, Escherichia coli were inoculated into the bladder and, at
      later sacrifice, bacterial culture was undertaken of renal parenchyma from the
      refluxing and non-refluxing kidneys. Positive cultures of the same E. coli were
      obtained from 33% of refluxing kidneys with pyelonephritic renal scars, 23% of
      refluxing kidneys without scars and 21% of non-refluxing kidneys. Although other
      aspects of the experiments confirmed that a combination of urinary infection,
      vesicoureteric reflux and intra-renal reflux is a necessary precondition for
      renal scarring, these findings indicate that reflux plays a role in the
      pathogenesis of renal scarring over and above a means whereby pathogens gain
      access from the lower urinary tract to the renal substance. Possible mechanisms
      are discussed.

PMID- 10071536
TI  - Detection of secondary tumours in patients with renal carcinoma: comparative
      study of ex vivo ultrasonography and histological examination.
AB  - Seventeen kidneys removed from patients with renal carcinoma were submitted to ex
      vivo ultrasonography and then to serial pathological examination in an attempt to
      detect secondary tumours in apparently normal tissue. Ex vivo ultrasonography
      failed to reveal further tumours, but 2 lesions measuring 5 and 8 mm were found
      on pathological examination. These preliminary data suggest that intra-operative
      ultrasonography may be of little value in detecting secondary tumours in
      conservative surgery for renal carcinoma.

PMID- 10071537
TI  - Bladder contractility and idiopathic detrusor instability in the female.
AB  - Twenty females with pure stress urinary incontinence (Group A) were studied
      clinically and urodynamically together with 20 stress incontinent women with
      idiopathic detrusor instability (Group B) and 20 controls (Group C). Forty
      females with the idiopathic urge syndrome, 20 with detrusor instability (motor
      urgency, Group D) and 20 with stable bladders (sensory urgency, Group E) were
      also investigated. Detrusor contractility, assessed on the basis of strength and
      velocity parameters derived from pressure flow data, was increased in the
      unstable groups. In particular, the maximum mechanical power (per unit of bladder
      wall surface area) generated by the contracting detrusor during voiding was
      higher in the unstable patients, this was also the case when estimating maximum
      bladder contraction velocity. No significant difference in these parameters was
      found in the patients with sensory urgency when compared with the controls and
      with the women with stress urinary incontinence, nor was there any significant
      difference between patients with motor urgency and the stress incontinent
      patients with detrusor instability. The enhanced contractile capability could be
      explained in the unstable stress incontinent group by a reduced threshold of
      stretch receptors in the urethral walls. If this were the case, urine running
      through the urethra at the beginning of voiding would be able to activate a
      urethrovesical reflex which may augment micturition contractions. In the group
      with the idiopathic urge syndrome one could speculate that sensory and motor
      urgency are due to the same neurological disorder (i.e. possibly a reduction in a
      tonic inhibitory or modulatory device) that would affect detrusor mechanics at
      different levels of the nervous system, resulting in different contractile
      capabilities.

PMID- 10071538
TI  - Intravesical instillation of oxybutynin hydrochloride for detrusor hyper
      reflexia.
AB  - The effect of intravesical oxybutynin hydrochloride on detrusor behaviour was
      studied in 15 patients with urinary incontinence due to detrusor hyper-reflexia
      by ambulatory bladder monitoring. Twelve patients had a reduction in the
      frequency and amplitude of hyper-reflexic contractions and incontinence episodes
      following oxybutynin administration. Intravesical oxybutynin may have a role in
      the management of patients on intermittent self-catheterisation with detrusor
      hyper-reflexia who cannot tolerate the side effects of anticholinergic agents,
      including oxybutynin.

PMID- 10071539
TI  - Encrusted cystitis: aetiology, clinical aspects and management.
AB  - Encrusted cystitis is a rare condition characterised by the formation of
      calcified plaques adherent to or embedded in the bladder mucosa. Although chronic
      infection with urea-splitting organisms is a prerequisite, other factors seem to
      play an important role in its development. We report our experience of 4 such
      cases in which encrusted cystitis presented with various symptoms, produced
      different pathological abnormalities and was treated by different means in each
      patient.

PMID- 10071540
TI  - Is abnormal electrosensitivity in the lower urinary tract a sign of neuropathy?
AB  - The threshold of sensitivity to electrical stimulation was determined in several
      parts of the lower urinary tract in 436 consecutive patients. In the groups with
      different patterns of disturbed sensation a higher incidence of neuropathy was
      found than in the group with a normal sensation. Further neurological
      investigation revealed abnormal innervation in 29% of patients who lacked
      electrosensitivity in one or more parts of the lower urinary tract but who had
      shown no previous evidence of neuropathy.

PMID- 10071541
TI  - Alternatives to urinary diversion with a bag: results in 100 patients.
AB  - One hundred patients underwent surgery to free them from a cutaneous urinary
      diversion (n = 59) or to avoid having one (n = 41). The reconstruction was
      tailored to the needs of the patient: 7 had a simple undiversion, 35 a complex
      undiversion and 58 a continent suprapubic diversion. The outcome was satisfactory
      in 97%. Two patients were rediverted to an ileal conduit. The simpler the
      reconstruction the lower the re-operation rate: simple undiversion 0%, complex
      undiversion 20%, Mitrofanoff 42%, Kock pouch 69%. In spite of the high
      complication rate, there is a strong demand for such reconstructions and a high
      satisfaction rate amongst patients.

PMID- 10071542
TI  - Mechanical characteristics of tubular and detubularised bowel for bladder
      substitution: theory, urodynamics and clinical results.
AB  - A theoretical analysis of the mechanics of tubular and detubularised bowel
      bladders is presented. The results are compared with clinical findings following
      bladder substitution with the tubular ileocaecal and the detubularised urethral
      Kock reservoir. The theoretical results are consistent with clinical observations
      showing that detubularisation increases reservoir capacity substantially, delays
      the onset and reduces the amplitude of the pressure rise produced by
      contractions. These findings account for the markedly improved nocturnal
      continence (80 versus 17% at 2 years), the longer voiding intervals (4 versus 2.5
      h at 1 year) and the predisposition to urinary retention (25 versus 0% at 1 year)
      with detubularised bladder substitution. A simple equation is derived to
      calculate the capacities of both near-spherical and cylindrical reservoirs. The
      capacity of the U pouch is calculated to be less than that of the W-shaped, S
      shaped and Kock reservoirs. Altering the shape of a reservoir from spherical to
      ellipsoid is calculated to have only a slight effect on its mechanical
      characteristics. Consequently the essence of detubularisation is to create a
      reservoir with high capacity, while shape is of secondary importance.

PMID- 10071543
TI  - Comparison of reagent strip (dipstick) and microscopic haematuria in urological
      out-patients.
AB  - Dipstick (reagent strip) and microscopic urine analysis for haematuria was
      performed prospectively on 1000 consecutive urine samples taken from urological
      out-patients. Haematuria was present in 185 samples (18.5%) and absent in 687
      (68.7%) using both tests; 98 samples (9.8%) had dipstick haematuria that was not
      confirmed by microscopy and 30 samples (3%) had microscopic haematuria that was
      missed on dipstick urine analysis. Dipstick urine analysis had a sensitivity of
      86.1% and a specificity of 85%. This study confirms that reagent strip testing
      for haematuria has both false positive and false negative results and indicates
      that cytoscopy should be considered in all patients with suspected haematuria.

PMID- 10071544
TI  - Late erosion. A new complication of artificial urinary sphincters.
AB  - A hitherto unreported long-term complication of artificial sphincter implantation
      -delayed erosion--is described.

PMID- 10071545
TI  - The effect of prostatic capsule perforation on the absorption of irrigating fluid
      during transurethral resection.
AB  - Thirty patients undergoing transurethral resection of the prostate using ethanol
      tagged irrigating fluid were investigated in order to study the effects of a
      breach in the prostatic capsule. Measurements were made of end-tidal ethanol (ET
      ethanol) in the expired air, serum glycine and sodium, haemoglobin, blood loss
      and volumetric determination of irrigating fluid absorption. Perforation of the
      prostatic capsule occurred in 13 patients (Group P), with 17 judged to have no
      perforation (Group NP). In all Group NP patients the ET-ethanol remained below
      0.05/1000, serum sodium decreased by < or = 3 mmol/l and serum glycine remained <
      1.5 mmol/l. ET-ethanol was significantly increased in Group P, rising to between
      0.1 and 0.45/1000 in 5 patients, 3 of whom showed a reduction in serum sodium > 5
      mmol/l. Five patients in Group P demonstrated significantly raised serum glycine
      concentrations up to 15 mmol/l. These findings suggest that perforation of the
      prostatic capsule may lead to rapid absorption of irrigating fluid, and that ET
      ethanol monitoring is a useful method of detecting this quickly.

PMID- 10071546
TI  - Fluid absorption and circulating endotoxins during transurethral resection of the
      prostate.
AB  - Recent publications report increased cardiovascular morbidity and mortality after
      transurethral prostatic resection (TURP). Repeated breath-ethanol monitoring with
      a new infrared device permits a highly sensitive peroperative registration of
      fluid absorption. A prospective study in 52 patients revealed surprisingly high
      rates of intravascular fluid loads without clinical manifestations. Only 4
      patients developed clinical signs of the TUR syndrome. Immunological work-up in
      41 patients demonstrated circulating endotoxins and significant rise of
      endogenous tumour necrosis factor (TNF) in 3 of these patients. In 11 patients
      transient endotoxins could be detected during resection under prophylactic
      parenteral antibiosis. In the face of less invasive approaches to benign
      prostatic hyperplasia, close intraoperative monitoring and antibiotic coverage
      should be demanded as a routine procedure during TURP. Elective surgery should be
      delayed until appropriate antibiotic therapy has been given.

PMID- 10071547
TI  - Effect of transurethral resection of prostate on plasma hormone levels in benign
      prostatic hyperplasia.
AB  - Circulating levels of pituitary and adrenal hormones were measured in patients
      with benign prostatic hyperplasia before and after transurethral resection of the
      prostate (TURP). TURP caused a significant increase in plasma LH levels 2 weeks
      and 3 weeks after surgery. The plasma prolactin level decreased significantly 3
      weeks after prostatectomy but plasma concentrations of FSH and ACTH were
      unchanged. TURP did not alter circulating levels of aldosterone, cortisol, DHEA-S
      and testosterone. These data suggest that the human prostate has a role in
      regulating the pituitary secretion of LH and prolactin.

PMID- 10071548
TI  - Long-term treatment of benign prostatic hyperplasia with alfuzosin: a 12-18 month
      assessment. BPHALF Group.
AB  - In order to assess the efficacy and safety of alfuzosin, an alpha-1 blocker, in
      symptomatic patients with benign prostatic hyperplasia (BPH), 131 patients who
      had completed a 6-month placebo-controlled trial conducted on parallel groups
      entered a 12-month open study; 122 patients were treated with alfuzosin for 12
      months and 56 patients for 18 months. After 12 months, all obstructive and
      irritative symptoms assessed according to the Boyarsky scale were significantly
      improved, as were peak flow rates in obstructed patients and mean flow rates and
      residual urine in the whole population. Voiding symptoms showed sustained
      improvement after treatment for 12 to 18 months. Only 5.3% of patients
      experienced vasodilatory side effects, none of which led to withdrawal from the
      study. No side effect related to long-term administration was reported. Alfuzosin
      has a beneficial effect on voiding symptoms in patients with BPH and can be
      safely used in long-term administration.

PMID- 10071549
TI  - Plasma sialic acid in patients with prostate cancer.
AB  - Serum sialic acid (N-acetylneuraminic acid) was evaluated as a tumour marker for
      prostate cancer and compared with serum prostate specific antigen (PSA). The
      records of 35 patients suffering from prostate cancer (9 with bone metastases)
      were analysed and compared with those of 21 healthy individuals. Total serum
      sialic acid was significantly elevated among the cancer patients. Levels in
      patients with distant metastases were significantly higher than in those with
      locally restricted disease and normal individuals, whereas no such difference was
      seen between the latter 2 groups. A direct association between serum sialic acid
      and tumour T category and grade could not be established. The difference between
      the cancer and the control groups was reflected more significantly by PSA. As
      sialic acid lacks tumour specificity, it is not helpful in screening for prostate
      cancer, yet might contribute towards the early detection of tumour progression
      and metastases during both therapy and follow-up.

PMID- 10071550
TI  - Oral cyclophosphamide for the management of hormone-refractory prostate cancer.
AB  - Thirty patients with hormone-refractory prostate cancer were treated with cycles
      of oral cyclophosphamide (100 mg/m2/day for 14 days, with a 14-day gap). Eighteen
      patients had a significant improvement in symptoms of advanced disease, 6 had
      objective partial remissions and 13 had stabilisation of disease (criteria of
      National Prostatic Cancer Project). The median survival from the time of
      diagnosis was 33.3 months, and from the commencement of cyclophosphamide 12.7
      months. The treatment was well tolerated. oral cyclophosphamide is active in the
      treatment of advanced hormone-refractory prostate cancer and yields symptomatic
      and objective remissions without undue side effects. This observation requires
      validation, with further testing of its impact on survival in randomised clinical
      trials.

PMID- 10071551
TI  - Combination therapy with flutamide and the LHRH agonist [D-Trp6, des-Gly
      NH(2)10]LHRH ethylamide in stage C prostatic carcinoma.
AB  - A series of 115 previously untreated patients displaying clinical stage C
      prostatic carcinoma with no evidence of distant metastases received combination
      therapy using the antiandrogen flutamide and the LHRH agonist [D-Trp6, des-Gly
      NH(2)10]LHRH ethylamide; the average follow-up was 3.9 years. Twenty-eight
      patients showed treatment failure with a probability of disease-free survival of
      91.2% at 2 years. Twenty patients died from prostate cancer and 10 from other
      causes, the survival probability being 93.4% at 2 years. Local control was
      achieved rapidly in all patients. Urinary obstruction and hydronephrosis were
      corrected in all cases. When compared with data obtained after single endocrine
      therapy (orchiectomy or oestrogens) or radiotherapy, the treatment failure rate
      at 2 years was more than 3.0-fold lower after combination therapy (8.8%) than
      monotherapy (28.4%). The death rate 2 years after the start of combination
      therapy was 6.6% and was on average 22.2% (3.6-fold higher) in the studies using
      monotherapy (orchiectomy or oestrogens) or radiotherapy. The present data suggest
      that treatment of prostate cancer with combination therapy before clinical
      evidence of dissemination of disease permits more efficient control of local
      disease and a decreased rate of progression to metastatic disease.

PMID- 10071552
TI  - Ultrastructural features of penile tissue in impotent men.
AB  - Penile erection is related to the integrity of penile tissue. In order to study
      the ultrastructural histopathological changes in penile erectile tissue in
      impotent men, biopsies were taken from 29 impotent and 5 normal patients during
      surgical treatment. Light microscopy revealed insignificant histological changes
      and various degrees of fibrotic change in the corpora cavernosa of impotent men,
      and electron microscopy revealed severe myopathic, fibrotic changes in the penile
      tissue. These non-specific changes could not be used to determine the aetiology
      of impotence, and the relationship between the ultrastructural appearances, the
      causes of impotence and the results of treatment was unclear. Further studies are
      required to establish the value of intracorporeal biopsy in selecting treatment
      for impotent patients.

PMID- 10071553
TI  - Testicular morphology and function in varicocele patients: pre-operative and post
      operative histopathology.
AB  - The organic effects of varicocele on testicular histology were studied in
      bilateral testicular biopsies obtained from 30 infertile men during varicocele
      repair and 3 to 6 months post-operatively, using light microscopy. Before surgery
      and at follow-up, semen analyses were performed. The results showed a substantial
      improvement in semen quality in 22 cases post-operatively. Pre-operative biopsies
      showed depressed spermatogenesis with a predominant picture of maturation arrest,
      sloughing of spermatogenic epithelium, an increase in Leydig cells, thickening of
      tubular basement membranes and interstitial blood vessel walls with narrowing of
      their lumina, and increased deposition of interstitial fibrous tissue. Post
      operatively, spermatogenesis improved in 22 cases, with increased mean tubular
      scores together with diminution in epithelial cell sloughing. The increased
      prominence of Leydig cells reverted to normal in 18 cases. The changes in tubular
      basement membranes, interstitium and interstitial blood vessels were unaffected.

PMID- 10071554
TI  - Histological and histochemical study of the vesicoureteric junction in infancy
      and childhood.
AB  - The morphology of the vesicoureteric junction was compared using 19 post mortem
      specimens obtained from male and female Afro-American and Caucasian children with
      an age range of 1 to 72 months (mean 4). All specimens were serially sectioned
      and the tissues processed using standard histological and histochemical
      techniques (acetylcholinesterase ?AChE? and pseudocholinesterase ?PChE?). The
      results failed to reveal any differences in the structure of the vesicoureteric
      junction with respect to age, sex and ethnic origins. The vesicoureteric junction
      comprised 3 histologically and histochemically distinct smooth muscle components.
      Ureteric muscle formed a complete inner layer rich in PChE which continued beyond
      the ureteric orifices to merge distally with the superficial trigone. An
      intermediate layer of muscle was also demonstrated whose constituent muscle cells
      possessed specific histological features and which was rich in both AChE and
      PChE, which is distinct from that derived from the ureter and detrusor. The
      presence of detrusor muscle on the outer aspect of the juxtavesical segment of
      ureter rich in AChE was also confirmed. While this study, using histochemical
      studies in infants and children, did not reveal any differences in the structure
      of the vesicoureteric junction with respect to age, sex or ethnic origin, an
      intermediate layer of muscle was identified with histochemical characteristics
      more like that of the male genital tract than that derived from the ureter or
      detrusor muscle.

PMID- 10071555
TI  - Localised amyloidosis of the prostate.

PMID- 10071556
TI  - Localised amyloidosis of the urinary bladder.

PMID- 10071557
TI  - Malakoplakia of epididymis associated with testicular infarction.

PMID- 10071559
TI  - Manual avulsion of the testis.

PMID- 10071558
TI  - Spermatocytic seminoma in a maldescended testis.

PMID- 10071560
TI  - Fibroepithelial polyp of the ureter.

PMID- 10071561
TI  - Bilateral ureteric strictures after intravesical mitomycin C.

PMID- 10071562
TI  - Response of carcinoma of the prostate to withdrawal of flutamide.

PMID- 10071563
TI  - Human papillomavirus-related bladder cancer following renal transplantation.

PMID- 10071564
TI  - Symptomatic intermittent bladder acontractility after clam cystoplasty.

PMID- 10071565
TI  - Vesicocolic fistula following suprapubic catheterisation.

PMID- 10071566
TI  - Vicarious excretion of intravenous contrast material in a patient with renal
      trauma.

PMID- 10071567
TI  - Laparoscopic nephroureterectomy for malignancy: vaginal route for retrieval of
      intact specimen.

PMID- 10071568
TI  - Temporary occlusion of the bladder by sutures for intractable bleeding.

PMID- 10071569
TI  - Catheter valves.

PMID- 10071570
TI  - Re: randomised study of the effect of midnight versus 0600 removal of urinary
      catheters. H. Crowe et al. Br. J. Urol., 71, 306-308, 1993.

PMID- 10071572
TI  - The adverse effects of short-term urinary catheterisation.

PMID- 10071571
TI  - Re: Effectiveness of haematuria clinics. J. P. Britton. Br. J. Urol., 71, 247
      252, 1993.

PMID- 10071573
TI  - Re: Risk of bacteraemia during extracorporeal shock wave lithotripsy. T. C.
      Gasser and R. Frei. Br. J. Urol., 71, 17-20, 1993.

PMID- 10071574
TI  - Re: Delayed presentation of posterior urethral valves. S. A. Merchant et al. Br.
      J. Urol., 69, 318-319, 1992.

PMID- 10071575
TI  - Re: Endometrioid carcinoma of the prostate. The diagnostic value of Leu7 and
      prostatic specific antigen. N. E. Stavropoulos et al. Br. J. Urol., 71, 309-312,
      1993.

PMID- 10071576
TI  - Re: Treatment of advanced localised prostatic cancer by orchiectomy,
      radiotherapy, or combined treatment. A Medical Research Council Study. G. J.
      Fellows et al. Br. J. Urol., 70, 304-309, 1992.

PMID- 10071577
TI  - Ethics and xenotransplantation.

PMID- 10071578
TI  - Soft-tissue images. Persistent left superior vena cava.

PMID- 10071579
TI  - Musculoskeletal images. Malignant transformation in familial osteochondromatosis?

PMID- 10071580
TI  - Radiology for the surgeon. Soft-tissue. Case 25. Bronchial carcinoid.

PMID- 10071581
TI  - Radiology for the surgeon. Musculoskeletal. Case 2: inferior dislocation of the
      glenohumeral joint (luxatio erecta).

PMID- 10071582
TI  - Xenotransplantation.
AB  - As transplantation waiting lists lengthen because of the shortage of donor
      organs, the death rates of patients continue to rise. Xenotransplantation offers
      the potential to solve the problem of organ shortage br providing an unlimited
      supply of healthy donor organs. However, there are several barriers to
      xenotransplantation, including graft rejection, potential xenozoonosis,
      physiologic incompatibilities and ethical concerns. Experimental
      xenotransplantation studies continue in several areas, ranging from tissue to
      whole- organ grafting. Clinical studies continue in the area of tissue
      xenotransplantation. Trials with extracorporeal xenografts in an acute setting to
      support fulminant organ failure are likely to begin in the near future. The
      reintroduction of whole-organ xenotransplantation must be based on sound
      scientific analysis with broad societal input so as to offer the maximal benefit
      to transplant recipients and their families.

PMID- 10071583
TI  - Trauma and critical care: introduction, recent advances and "ownership" in the
      critical care unit.

PMID- 10071584
TI  - Total knee replacement: should it be cemented or hybrid?
AB  - OBJECTIVE: To compare the complication rates associated with total knee
      arthroplasty against the types of fixation (hybrid or cemented), using a single
      total knee design (the anatomic modular knee [AMK] prosthesis). DESIGN: A
      prospective, nonrandomized, controlled trial. SETTING: University Hospital in
      London, Ont., a tertiary care teaching centre. PATIENTS: Two groups made up of
      484 knees in 395 patients (89 bilateral). INTERVENTIONS: In 260 knees a hybrid
      configuration (cemented tibia and noncemented femur) was used (group 1). In 224
      knees the femoral and tibial components were cemented (group 2). All patellae
      were cemented in both groups. MAIN OUTCOME MEASURES: Clinical results were
      assessed by The Knee Society Clinical Rating Scores at 3 months, 6 months and
      yearly intervals. Radiographic results were determined by 3-foot standing
      radiographs and at each follow-up visit standing knee radiographs, lateral and
      skyline views. Radiographs were analysed for alignment, presence or absence of
      radiolucent lines or changes in the position of the implant. All reoperations and
      nonoperative complications were recorded. RESULTS: At an average follow-up of 4.8
      years, 8 knees (1.6%) required reoperation. An analysis of the complications
      leading to reoperation demonstrated no difference between the 2 groups.
      CONCLUSIONS: There was no difference in outcome whether the femoral component was
      cemented or not. Medium-term results of the AMK are excellent with a very low
      reoperation rate.

PMID- 10071585
TI  - Bileaflet mechanical prostheses for aortic valve replacement in patients younger
      than 65 years and 65 years of age or older: major thromboembolic and hemorrhagic
      complications.
AB  - OBJECTIVE: To determine major thromboembolic and hemorrhagic complications and
      predictive risk factors associated with aortic valve replacement (AVR), using
      bileaflet mechanical prostheses (CarboMedics and St. Jude Medical). DESIGN: A
      case series. SETTING: Cardiac surgical services at the teaching institutions of
      the University of British Columbia. PATIENTS AND METHODS: Patients 2 age groups
      who had undergone AVR between 1989 and 1994 were studied. Group 1 comprised 384
      patients younger than 65 years. Group 2 comprised 215 patients 65 years of age
      and older. RESULTS: The linearized rates of major thromboembolism (TE) occurring
      after AVR were 1.54%/patient-year for group 1 and 3.32%/patient-year for group 2;
      the rates for major TE occurring more than 30 days after AVR were 1.13%/patient
      year for group 1 and 1.55%/patient-year for group 2. The crude rates for major TE
      occurring within 30 days of AVR were 1.04% for group 1 and 3.72% for group 2. The
      death rate from major TE in group 1 was 0.31%/patient-year and in group 2 was
      0.88%/patient-year. Of the major TE events occurring within 30 days, 100% of
      patients in both age groups were inadequately anticoagulated at the time of the
      event, and for events occurring more than 30 days after AVR, 45% in group 1 and
      57% in group 2 were inadequately anticoagulated (INR less than 2.0). The overall
      linearized rates of major hemorrhage were 1.54%/patient-year for group 1 and
      2.21%/patient-year for group 2. There were no cases of prosthesis thrombosis in
      either group. The mean (and standard error) overall freedom from major TE for
      group 1 patients at 5 years was 95.6% (1.4%) and with exclusion of early events
      was 96.7% (1.3%); for group 2 patients the rates were 90.0% (3.2%) and 93.7%
      (3.0%), respectively. The mean (and SE) overall freedom from major and fatal TE
      and hemorrhage for group 1 patients was 90.1% (2.3%) and with exclusion of early
      events was 91.2% (2.3%); for group 2 patients the rates were 87.9% (3.1%) and
      92.5% (2.9%), respectively. The 5-year rate for freedom from valve-related death
      for group 1 patients was 96.3% (2.1%) and for group 2 patients was 97.2% (1.2%).
      CONCLUSION: The thromboembolic and hemorrhagic complications after AVR with
      bileaflet mechanical prostheses occur more frequently and result in more deaths
      in patients 65 years of age and older than in patients years younger than 65
      years.

PMID- 10071586
TI  - Evaluation of the allograft-prosthesis composite technique for proximal femoral
      reconstruction after resection of a primary bone tumour.
AB  - OBJECTIVE: To evaluate clinical and functional outcomes resulting from the
      allograft-composite technique used for proximal femoral osteoarticular
      reconstruction in patients who had limb salvage surgery for primary bone tumours.
      DESIGN: A retrospective review of a prospectively gathered database to provide a
      descriptive study. SETTING: A tertiary care musculoskeletal oncology unit in a
      university hospital. PATIENTS AND INTERVENTIONS: Patients treated between 1987
      and 1993 were eligible for inclusion in this study if they met the following
      criteria: they were treated surgically for a primary malignant bone tumour; and a
      proximal femoral allograft-implant composite technique was used for the
      reconstruction. MAIN OUTCOME MEASURES: Major postoperative complications with
      emphasis on mechanical complications in the reconstructive composite implant.
      Functional outcome in a subset of patients using the 1987 and 1994 versions of
      the Musculoskeletal Tumor Society instrument, the Short-Form-36 and the Toronto
      Extremity Salvage Score. RESULTS: There were 5 mechanical and 2 infectious
      complications requiring surgical intervention. Functional scores were generally
      low. CONCLUSIONS: Our results suggest that the perceived benefits of the
      composite technique may accrue only to a few patients, partly owing to the risk
      of mechanical complications. Although these can be reduced by avoiding the use of
      cement in the host femur, the generally poor functional outcomes suggest that
      this technique needs to be studied further in this group of patients and compared
      with other reconstructive techniques, particularly the prosthetic implant.

PMID- 10071587
TI  - Retrograde esophageal balloon dilatation for caustic stricture in an outpatient
      clinic setting.
AB  - Caustic injury to the esophagus, with resultant esophageal stricture, is a
      challenge for the surgeon. These strictures require multiple esophageal
      dilatations, which are usually performed under general anesthesia and frequently
      under fluoroscopic control. Because of the risks of multiple general anesthetics
      and frequent radiation, a technique is described for retrograde esophageal
      balloon dilatation in an outpatient clinic setting without a general anesthetic
      or fluoroscopic control.

PMID- 10071588
TI  - Desmoid tumour. The risk of recurrent or new disease with subsequent pregnancy: a
      case report.
AB  - Desmoid tumours are rare, benign tumours arising from fibrous tissue in muscle
      fascia or aponeurosis. They are most common in women of child-bearing age and
      most often appear during or after pregnancy in this age group. The recommended
      treatment is wide surgical excision, if possible, but unresectable tumours may be
      treated with radiotherapy, anticancer drugs, nonsteroidal anti-inflammatory
      agents or antiestrogenic compounds. The recurrence rate is high and seems to be
      related to the achievement of resection margins free of tumour. The literature is
      not specific about how to counsel women who have had a desmoid tumour and
      subsequently wish to have a child. Patients should be advised that these tumours
      may be estrogen sensitive but subsequent pregnancy is not necessarily a risk
      factor for recurrence or development of new disease.

PMID- 10071589
TI  - Pancreatic polypeptide hyperplasia causing watery diarrhea syndrome: a case
      report.
AB  - Neuroendocrine tumours of the pancreas can secrete numerous peptides, leading to
      various recognizable clinical syndromes. The secretion of pancreatic polypeptide
      has been used as a marker for neuroendocrine tumours but is considered to be a
      biologically inert peptide. A 37-year-old woman had watery diarrhea syndrome from
      pancreatic polypeptide hyperplasia. Only 2 other reported cases in the literature
      have described pancreatic polypeptide hyperplasia; however, this is the first
      reported case in which the patient was successfully treated by surgical
      resection, with a 2-year follow-up. This report and review of the literature
      illustrate that pancreatic polypeptide hypersecretion may present as a clinical
      endocrinopathy.

PMID- 10071590
TI  - Carcinoids of the common bile duct: a case report and literature review.
AB  - Carcinoids of the extrahepatic bile ducts and particularly the common bile duct
      are extremely rare. A 65-year-old woman presented with obstructive jaundice.
      Laboratory and imaging studies gave results that were consistent with an
      obstructing lesion in the common bile duct. In this case, a stent was inserted
      initially to decompress the bile ducts. Subsequently a laparotomy and
      pancreaticoduodenectomy were performed and a tissue diagnosis of carcinoid of the
      common bile duct was made. The patient was well with no evidence of recurrence 17
      months postoperatively. The authors believe this is the 19th reported case of an
      extrahepatic bile duct carcinoid.

PMID- 10071592
TI  - Additive action of gemcitabine (2',2'-difluorodeoxycytidine) and 2
      chlorodeoxyadenosine on murine leukemias L1210 and P388.
AB  - The influence of 2-chlorodeoxyadenosine (2-CdA) and 2',2'-difluorodeoxycytidine
      (Gemcitabine, dFdC) on the survival time of mice bearing L1210 and P388 leukemias
      was investigated. Seventy-two male CD2F1 strain mice were used in the experiment.
      They were given 2-CdA (20 mg/kg) on days 1-5 after inoculation with leukemic
      cells (day 0) i.p. or dFdC (20 mg/kg) on days 1, 4, 7, and 10 i.p. The drugs were
      administered alone and in combination (sequential therapy) according to the
      following schedules: 2-CdA and dFdC at the same time at the doses given above; 2
      CdA before dFdC, sequential therapy (2-CdA on days 1-5, then dFdC on days 6, 9,
      12, 15); dFdC before 2-CdA, sequential therapy (dFdC on days 1, 4, 7, 10 and then
      2-CdA on days 11-15). The animals were observed daily for survival for a minimum
      of 60 days. The efficacy of the therapy against leukemia (defined as the increase
      in lifespan, ILS) was assessed as the percentage of the median survival time
      (MST) of the treated group (T) to that of the control group (C): ILS =
      [(MSTc/MSTT-1] x 100. The survival time of mice bearing L1210 or P388 leukemia
      treated with dFdC before 2-CdA was significantly prolonged as compared with the
      animals receiving these agents separately. The prolongation of the survival time
      of the treated mice (ILS) compared with the untreated was 300% in case of L1210
      and 241% in case of P388 leukemia. The combinations 2-CdA before dFdC and
      simultaneous injections of both drugs were not more effective than the treatment
      with dFdC alone. In case of L1210 leukemia, mice treated with these regimens
      showed a survival time similar to those treated with dFdC alone, although the
      survival time of mice bearing P388 leukemia treated with these regimens was
      shorter than that of mice given dFdC singly. Our study revealed that the most
      effective treatment schedule in both leukemias was dFdC given before 2-CdA. The
      results confirm the additive action of dFdC and 2-CdA.

PMID- 10071593
TI  - Utility of routine postoperative laboratory studies in patients undergoing
      potentially curative resection for adenocarcinoma of the colon and rectum.
AB  - In an effort to lower healthcare costs, this study was undertaken to evaluate the
      utility of routine postoperative (PO) laboratory studies and determine whether
      abnormalities alter patient (PT) care. This was a retrospective review of 105 PTs
      undergoing elective curative resection for colorectal cancer. A serum electrolyte
      and liver panel and a hematologic panel were drawn in all PTs. OF 8749 total
      laboratory values obtained, 5894 (67%) were normal. Two of these (0.03%) elicited
      a therapeutic intervention. Of the 2004 values that were low (23%), 103 (5.1%)
      elicited a therapeutic response. Of the 851 that were high (10%), 21 (2.5%)
      elicited a therapeutic response. Of 2089 preoperative laboratory values, 252
      (12%) were abnormal, but in only 15 incidences in 9 PTs was any action taken.
      Three PTs required potassium supplementation and 6 PTs were transfused packed red
      blood cells before surgery. In the PO period 2603 laboratory values of 6660
      obtained (39%) were abnormal. Of these, 735 (28%) were high and 1868 (72%) were
      low. Twenty of 735 (27%) high values triggered a therapeutic response that most
      commonly required administration of insulin for elevated serum glucose in 17 of
      197 occasions in five diabetic PTs. On three occasions potassium was removed from
      intravenous fluids. Five of 275 (1.8%) low calcium values were treated in five
      patients. Potassium was replaced in 17 of 32 occasions in 14 patients where it
      was low. In this group of PTs, PO serum potassium, hemoglobin levels, and serum
      glucose in diabetics were the only values important in making therapeutic
      decisions. If laboratory studies can be streamlined into only those necessary,
      substantial savings in health care will be seen without sacrificing quality
      medical care.

PMID- 10071594
TI  - Radiotherapy for the treatment of giant cell tumor of the spine: a report of six
      cases and review of the literature.
AB  - Optimal treatment for giant cell tumors in the axial skeleton (GCTS) remains
      challenging. Surgical excision remains the treatment of choice, but the potential
      spinal cord injury may limit the extent of resection. We report the long-term
      results of treatment of six patients diagnosed with giant cell tumor of the spine
      treated with radiotherapy and review the literature regarding therapy. Between
      1971 and 1995, six patients with GCTS were treated with conservative surgery and
      radiotherapy. The surgery consisted of either biopsy or subtotal resection of
      tumor. The involved vertebrae were then irradiated with doses ranging from 3000
      to 5400 cGy. The mean follow-up was 13 years, and three of six patients had
      follow-up of 17 or more years. Five of six patients are alive with no evidence of
      disease. One is alive with disease, although it is not clinically apparent. No
      patient was lost to follow-up. We conclude that radiotherapy is useful in the
      management of GCTS and that conservative surgery with local radiotherapy is a
      reasonable treatment alternative for tumors that cannot be completely excised or
      in which surgery would result in significant functional morbidity. Although there
      is no clear dose response, review of the literature suggests that doses ranging
      from 3500 to 4500 cGy are safe and effective in controlling giant cell tumor.

PMID- 10071595
TI  - Cisplatin and infusional cytosine arabinoside for the treatment of colorectal
      adenocarcinoma: a phase II trial.
AB  - Based on the in vitro and in vivo synergy between cytosine arabinoside (Ara-C)
      and cis-diamminedichloroplatinum (cisplatin), we designed a phase II trial of Ara
      C with cisplatin for patients with colorectal adenocarcinoma. Forty-eight
      eligible patients received continuous infusion Ara-C, 30 mg/m2/day over 72 hr,
      plus cisplatin, 30 mg/m2 for three doses at hours 12, 36, and 60 of the Ara-C
      infusion. The objective partial response rate for patients with colon carcinoma
      was 3% (1/32 patients; 95% CI, 0-16%) with a median response duration of 2.8
      months. None of the 16 patients treated for rectal carcinoma responded.
      Myelosuppression was the most severe toxicity. Significant gastrointestinal and
      hepatic toxicities occurred in a small number of patients. Nephrotoxicity and
      neurotoxicity were mild. We conclude that the prolonged infusion of Ara-C in
      combination with divided doses of cisplatin offers no significant therapeutic
      advantage.

PMID- 10071596
TI  - Hepatic artery administration of paclitaxel.

PMID- 10071597
TI  - Taxanes in the treatment of breast cancer: a prodigy comes of age.
AB  - The taxanes, paclitaxel and docetaxel, are among the most promising new agents in
      the treatment of breast cancer. Responses are routinely seen in > 30% of patients
      with metastatic disease, including those who have previously received
      anthracyclines. Combination therapy has increased response rates but as yet has
      not improved the overall survival of patients with metastatic disease. Improved
      survival with the addition of paclitaxel to standard adjuvant therapy reported in
      a recently completed trial suggests the true impact of the taxanes has not yet
      been realized.

PMID- 10071598
TI  - Treatment options in androgen-independent prostate cancer.
AB  - Metastatic prostate cancer is a leading cause of cancer-related death in men.
      Although most patients will respond to androgen ablation as initial systemic
      therapy, nearly all patients will develop androgen-independent prostate cancer
      (AI CaP) and will succumb to the disease. Advances in molecular biology have
      demonstrated mutations in and persistent expression of the human androgen
      receptor in metastatic disease. Furthermore, recent evidence indicates that an
      apoptotic block through p53 mutations or bcl-2 overexpression may have a
      potential role in the poor responses seen with standard chemotherapy. Presently,
      the six general treatment options available for AI CaP are best supportive care,
      radiation therapy, radioisotopes, secondline hormonal therapy, chemotherapy
      (single agent or combination), and investigational therapies such as monoclonal
      antibodies, cyclin-dependent kinase inhibitors, matrix metalloproteinase
      inhibitors, and antiangiogenesis agents, among others. None of these modalities
      have produced durable remissions, although some have demonstrated palliative
      benefit. The next generation of clinical trials should not consist of futile
      hormonal manipulations or repetitive chemotherapy. Therapeutic strategies aimed
      at circumventing molecular blocks to cell death or targeting unique cancer
      molecules and genes will be more likely to improve quality of life and longevity.
      Furthermore, the aggressive use of palliative care will ensure effective caring
      for patients and the healing of families in the absence of cure.

PMID- 10071599
TI  - Antifungal and antiviral agents: a review.

PMID- 10071600
TI  - Discovery and development of antineoplastic agents from natural sources.
AB  - Nature has provided many effective anticancer agents in current use, such as the
      microbially derived drugs; dactinomycin; bleomycin and doxorubicin; and the plant
      derived drugs, vinblastine, irinotecan, topotecan, etoposide, and paclitaxel. The
      search for novel antitumor agents from natural sources continues through
      collaboration among scientists worldwide in the investigation of coral reefs,
      rainforests, and deep subsurface thermal vents for novel bioactive compounds. The
      potential for drug discovery is being further enhanced by recent advances in
      procedures for microbial cultivation and the extraction of nucleic acids from
      environmental samples, resulting in the identification of novel microbes that
      provide a vast untapped reservoir of genetic and metabolic diversity.
      Manipulation of the biosynthetic pathways of microbial polyketides through
      genetic engineering permits the biosynthesis of bioactive polyketides not
      generated naturally.

PMID- 10071601
TI  - The war on healthcare professionals and healthcare delivery.

PMID- 10071602
TI  - [Diagnosis and therapy of tumor of Vater's ampulla].
AB  - BACKGROUND AND OBJECTIVE: Complete removal of tumours of the ampulla (papilla) of
      Vater is generally recommended, because of the known adenoma-carcinoma sequence
      yet the uncertainty regarding diagnosis of dignity of such tumours. The aim of
      this study was tho analyse different treatment concepts on the basis of data from
      a personal series of cases. PATIENTS AND METHODS: Clinical, laboratory and
      histological data as well as treatment and course in nine patients (three women,
      six men; mean age 62 [46-82] years) with ampulla of Vater adenoma, treated at one
      hospital, were analysed retrospectively. The patients had been followed for 6-36
      months. RESULTS: All tumours had been removed endoscopically. Partial
      duodenopancreatectomy had subsequently been performed in two patients because of
      severe dysplasia. One tumour with moderately severe dysplasia had recurred
      locally within two months of endoscopic removal and was resected transduodenally.
      There had been no further recurrences 3 to 36 months later. CONCLUSION: If there
      is no evidence of malignity and frequent follow-up can be ensured, endoscopic
      removal of a tumour of the ampulla of Vater is justified. Otherwise transduodenal
      excision of the ampulla or partial duodenopancreatectomy should be undertaken.

PMID- 10071603
TI  - [Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy
      with octreotide].
AB  - HISTORY AND FINDINGS: Magnetic resonance imaging (MRI) of the central nervous
      system was performed on a 72-year-old woman who was hyperthyroid without
      suppression of the thyroid-stimulating hormone (TSH) and had complained of a
      recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in
      diameter, in the anterior pituitary. The clinical symptoms were marked by a long
      standing monosymptomatic illness of rapidly changing mood swings with depressive
      and manic phases. INVESTIGATIONS: Endocrinological-biochemical tests showed
      hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH:
      2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the
      anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a
      5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified
      the mass as a retrosternal goitre. TREATMENT AND COURSE: As an operation on the
      anterior pituitary would have carried a high risk for the patient who was in a
      poor general condition and she had refused to be operated, treatment with
      octreotide, a long-acting somatostatin analogue, was initiated. This achieved a
      euthyroid state with partly suppressed TSH, and the patient's emotional swings
      ceased. CONCLUSION: If hyperthyroidism coexists with non-suppressed TSH levels, a
      TSH-producing hypophyseal adenoma should be considered in the differential
      diagnosis despite its rarity. Octreotide administration is an effective and safe
      treatment and is the method of choice, especially when there are
      contraindications to surgical resection of the anterior pituitary.

PMID- 10071604
TI  - [Marked hemosiderosis in myelodysplastic syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 68-year-old man was admitted because of
      symptoms of lumbar pain. He was known to have chronic anemia with ring
      sideroblasts and diabetes melitus and to be in heart failure. Three months before
      he had been given 7 units of red cell concentrate. On admission the outstanding
      features were brown discoloration of the skin, absent body hair, tachycardia,
      hepatomegaly and small testicles. INVESTIGATIONS: He had a normocytic anemia,
      hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency.
      The serum levels of iron, transferrin saturation and feritin were markedly
      elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer).
      Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed
      hepatomegaly. DIAGNOSIS, TREATMENT AND COURSE: The known myelodysplastic syndrome
      (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement,
      diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was
      unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron.
      But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The
      patient later died of the sequelae of hemosiderosis. CONCLUSION: Even when they
      have not required transfusions, patients with long-standing MDS should be
      examined regularly for the possible development of secondary hemosiderosis so
      that iron-chelating agents can be administered as needed.

PMID- 10071605
TI  - [Diagnosis of neuromuscular diseases: progress with molecular genetic
      techniques].

PMID- 10071606
TI  - [Leishmaniasis. Basic principles, clinical aspects, diagnosis and therapy].

PMID- 10071607
TI  - [Requirements for patient rooms from the public health viewpoint. Guidelines for
      renovation and construction].

PMID- 10071608
TI  - [Emil Kraepelin (1856-1926)--systematic physician in (German) psychiatry].

PMID- 10071609
TI  - Predicting failure of endovascular aneurysm repair.

PMID- 10071610
TI  - Disruption of skin perfusion following longitudinal groin incision for
      infrainguinal bypass surgery.
AB  - OBJECTIVE: The objective of our study was to investigate whether such an incision
      results in a reduction in blood flow, and therefore haemoglobin oxygen
      saturation, across the wound. DESIGN: Microvascular oxygenation was measured with
      lightguide spectrophotometry in 21 patients undergoing femoropopliteal or
      femorodistal bypass procedures. A series of measurements were made in the groin,
      medial and lateral to the surface marking of the femoral artery. The mean oxygen
      saturation on each side was calculated, and the contra-lateral groin was used as
      a control. The measurements were repeated at 2 and 7 days postop. RESULTS: Oxygen
      saturation in the skin of the operated groins was increased significantly from
      baseline at 2 days postop (f = 25.80, p < 0.001) and had begun to return to
      normal by day 7. The rise was more marked on the lateral side of the wound than
      on the medial (f = 12.32, p < 0.001). There was no such difference in the control
      groins. All wounds healed at 10 days. CONCLUSIONS: These results show a
      significant difference in skin oxygenation between the lateral and medial sides
      of the groin following longitudinal incision. This may contribute to the
      relatively high incidence of postoperative infection in these wounds.

PMID- 10071611
TI  - Transfection of small numbers of human endothelial cells by electroporation and
      synthetic amphiphiles.
AB  - OBJECTIVES: This study compared the efficiency of electroporation and synthetic
      amphiphiles. (SAINT-2pp/DOPE) in transfecting small numbers of human endothelial
      cells. METHODS AND RESULTS: Optimal transfection conditions were tested and
      appeared to be 400 V and 960 microF for electroporation and a 10:1 ratio for
      concentrations of SAINT-2pp/DOPE: plasmid. Using these conditions, cell
      concentrations were lowered step-wise and we were able to transfect as few as one
      thousand cells with both methods. For detection of transfection of a small number
      of cells a sensitive assay was needed (Luciferase). A plasmid containing the
      neomycin resistance gene was used to determine the transfection rate expressed in
      colony forming units by counting colonies after selection. At low plasmid
      concentrations this transfection rate was within the same range for both
      electroporation and SAINT-2pp/DOPE transfection. Fluorescent in situ
      hybridisation of metaphase chromosomes of transfected endothelial cells using the
      plasmid as a probe showed that stable integration was possible with both methods.
      CONCLUSIONS: Electroporation and a synthetic amphiphile, SAINT-2pp, provide the
      possibility of transfecting small numbers of cells resulting in stable
      integration of low plasmid concentrations. The availability of this technology is
      important in order to obtain functional endothelial cell lines from various human
      blood vessels for research purposes.

PMID- 10071612
TI  - Factors influencing the development of vein-graft stenosis and their significance
      for clinical management.
AB  - OBJECTIVES: To assess the influence of clinical and graft factors on the
      development of stenotic lesions. In addition the implications of any significant
      correlation for duplex surveillance schedules or surgical bypass techniques was
      examined. PATIENTS AND METHODS: In a prospective three centre study, preoperative
      and peroperative data on 300 infrainguinal autologous vein grafts was analysed.
      All grafts were monitored by a strict duplex surveillance program and all
      received an angiogram in the first postoperative year. A revision was only
      performed if there was evidence of a stenosis of 70% diameter reduction or
      greater on the angiogram. RESULTS: The minimum graft diameter was the only factor
      correlated significantly with the development of a significant graft stenosis
      (PSV-ratio > or = 2.5) during follow-up (p = 0.002). Factors that correlated with
      the development of event-causing graft stenosis, associated with revision or
      occlusion, were minimal graft diameter (p = 0.001), the use of a venovenous
      anastomosis (p = 0.005) and length of the graft (p = 0.025). Multivariate
      regression analysis revealed that the minimal graft diameter was the only
      independent factor that significantly correlated with an event-causing graft
      stenosis (p = 0.009). The stenosis-free rates for grafts with a minimal diameter
      < 3.5 mm, between 3.5-4.5 and > or = 4.5 mm were 40%, 58% and 75%, respectively
      (p = < 0.05). Composite vein and arm-vein grafts with minimal diameters > or =
      3.5 mm were compared with grafts which consisted of a single uninterrupted
      greater saphenous vein with a minimal diameter of < 3.5 mm. One-year secondary
      patency rates in these categories were of 94% and 76%, respectively (p = 0.03).
      CONCLUSIONS: A minimal graft diameter < 3.5 mm was the only factor that
      significantly correlated with the development of a graft-stenosis. However, veins
      with larger diameters may still develop stenotic lesions. Composite vein and arm
      vein grafts should be used rather than uninterrupted small caliber saphenous
      veins.

PMID- 10071613
TI  - Intraoperative transoesophageal echocardiography as an adjuvant to fluoroscopy
      during endovascular thoracic aortic repair.
AB  - OBJECTIVES: To define the utility of intraoperative transeophageal
      echocardiography (TEE) during endovascular thoracic aortic repair. DESIGN:
      Retrospective study. MATERIALS: Five patients underwent six transluminal
      endovascular stent-graft procedures for repair of thoracic aortic disease.
      METHODS: After induction of anaesthesia, a multiplane or biplane TEE probe was
      placed to obtain views of the diseased aorta. Both transverse and longitudinal
      planes of the aortic arch and descending thoracic aortic segments were imaged.
      The aortic pathology was confirmed by TEE and the proximal and distal extents of
      the intrathoracic lesion were defined. Doppler and colour-flow imaging was used
      to identify flow patterns through the aorta before and after stent-graft
      deployment. RESULTS: Visualisation and confirmation of the aortic pathology by
      ultrasonography was accomplished in all patients. TEE was able to confirm proper
      placement of the endograft relative to the aortic lesion after deployment and was
      able to confirm exclusion of blood flow into the aneurysm sacs. CONCLUSIONS: TEE
      may facilitate repair by confirming aortic pathology, identifying endograft
      placement, assessment of the adequacy of aneurysm sack isolation, as well as
      dynamic intraoperative cardiac assessment.

PMID- 10071614
TI  - Frame dislocation of body middle rings in endovascular stent tube grafts.
AB  - OBJECTIVES: To understand the cause, and propose a mechanism for frame
      dislocation in endovascular grafts. MATERIALS AND METHODS: Five tube grafts were
      explanted due to secondary distal leakage 15-21 months after operation. One
      bifurcated graft was removed during emergency operation after aortic rupture
      caused by secondary leakage. A second bifurcated graft was harvested from a
      patient with thrombotic occlusion of one limb, who died after transurethral
      prostatic resection. The inside of the grafts were examined endoscopically. The
      stent was inspected after removal of the fabric, broken ligatures were counted
      and examined by scanning electron microscopy. The fabric strength was tested by
      probe puncture. RESULTS: We found 17-44% of the stent ligatures of the body
      middle rings to be loose. The knots were intact. Degradation of the polyester
      textile was not observed. CONCLUSIONS: Continuous movements in the grafted aorta
      and blood pressure impose permanent stress to the stent frame and the polyester
      fabric resulting in morphological changes in the body middle ring of grafts. The
      clinical implications of the suture breakages are unknown although they may be
      related to distal secondary leakage in tube grafts.

PMID- 10071615
TI  - Level of amputation following failed arterial reconstruction compared to primary
      amputation--a meta-analysis.
AB  - OBJECTIVES: To determine if the level of amputation after failed vascular
      reconstruction was comparable to the level of amputation after primary
      amputation. DESIGN AND METHODS: Medline literature search (1975-1996), meta
      analysis. RESULTS: The odds ratio of transtibial to transfemoral (TT/TF)
      amputations was 927/657 = 1.41 (95% confidence limits: 1.278-1.561) in
      postrevascularisation amputation (PRVA) and 1590/1162 = 1.37 (95% confidence
      limits: 1.269-1.477) in primary amputation (PA) (p = 0.65). The pooled data show
      that the number of conversions from transtibial (TT) to transfemoral (TF)
      amputations due to amputation stump complications were 85/369 (23%) in PRVA
      against 93/752 (12.4%) in PA (p < 0.01). CONCLUSIONS: We could not detect any
      difference in TT/TF ratio between PRVA and PA. However, the risk of conversion
      i.e. reamputation to a higher level is higher after PRVA compared to PA. The
      chance of having a successful transtibial amputation is approximately 58% for
      postrevascularisation amputation as well as for primary amputations. An
      aggressive approach towards vascular reconstruction seems justified.

PMID- 10071616
TI  - Skeletal muscle tissue oxygen pressure distribution during early reperfusion
      after prolonged ischaemia.
AB  - OBJECTIVES: The aim of this study was to investigate the skeletal muscle tissue
      oxygen pressure (PtO2) distributions during early reperfusion (10-45 min) after
      prolonged ischaemia in a rat animal model. MATERIAL AND METHODS: Skeletal muscle
      ischaemia was induced in anaesthetised rats by applying a tourniquet on the left
      thigh for 3 h (group I) or 4 h (group II), and tissue oxygen pressure
      measurements were made after 10-45 min of reperfusion. Assessment of PtO2 was
      made by a multiwire Clark-type oxygen microelectrode, placed on the surface of
      the left tibialis anterior muscle. RESULTS: During reperfusion a similar PtO2
      pattern was evaluated after both 3 and 4 h of total ischaemia, where the sum PtO2
      distributions were shifted to the left associated with low tissue oxygen pressure
      values. After 10 min of reperfusion the median PtO2 was 0.28 kPa and 0.18 kPa, in
      groups I and II, respectively; after 45 min of reperfusion 0.61 kPa and 0.60 kPa,
      respectively. The median PtO2 in the non-ischaemic muscle in groups I and II were
      2.19 and 2.17 Pa. CONCLUSION: The results show that local skeletal muscle
      oxygenation is severely impaired during the initial 45 min of reperfusion after
      both 3 and 4 h of total muscle ischaemia with a slow-reflow phenomenon generally
      present, despite pronounced needs.

PMID- 10071617
TI  - Effect and outcome of balloon angioplasty and stenting of the iliac arteries
      evaluated by intravascular ultrasound.
AB  - OBJECTIVES: To document the mechanism of percutaneous transluminal angioplasty
      (PTA) and stenting of the iliac arteries, and to relate the effect to patency.
      MATERIALS AND METHODS: Thirty-seven stenotic iliac arteries were examined by
      intravascular ultrasound (IVUS) and arteriography before and after PTA, and after
      stent deployment (n = 16). The patients were followed prospectively by duplex
      scanning at 3, 6, 12, 18 and 24 months after the intervention. RESULTS: The
      effect of PTA was established by both compression and stretching with the major
      contribution arising from stretching. There were differences in the effect of PTA
      dependent on plaque morphology: in homogeneous eccentric lesions, stretching
      contributed significantly more than compression to the luminal gain, while
      stretching and compression contributed equally in concentric or heterogeneous
      plaques. Stenting of the arteries had no effect on the free luminal area as
      measured by IVUS. The primary 1-year patency rate was 72%. The patency was
      related to the free luminal area and diameter and the heterogenicity of the
      plaque as evaluated by IVUS. The arteriographic measurements did not have any
      predictive value. CONCLUSION: IVUS was able to document the effect of PTA and
      stenting in the iliac arteries, and predict the outcome. The luminal gain and
      reduction in degree of stenosis seemed to be accomplished primarily by stretching
      of the arteries and to a lesser extent by plaque compression. Stenting did not
      change the IVUS measurements. Patency was related to the size of the free lumen
      and the heterogenicity of the plaque.

PMID- 10071618
TI  - Antegrade visceral revascularisation via a thoracoabdominal approach for chronic
      mesenteric ischaemia.
AB  - OBJECTIVES: It has been suggested that patients with chronic visceral ischaemia
      are elderly and emaciated hence they may not tolerate antegrade visceral
      revascularisation via a thoracoabdominal approach. There are no studies to
      support this assumption. The purpose of this study is to assess the efficacy of
      this approach for the treatment of chronic visceral ischaemia. METHODS: Between
      1988 and 1996, 10 patients underwent antegrade visceral revascularisation for
      chronic visceral ischaemia via a thoracoabdominal approach and were followed-up
      for a mean of 40 months. Eight patients were treated with aorto superior
      mesenteric artery bypass and implantation of the coeliac axis in the graft and
      two patients with aorto superior mesenteric bypass alone. Graft patency was
      monitored with duplex scanning. RESULTS: There were no postoperative deaths in
      this series. Two patients developed postoperative pulmonary infections and
      required intubation for a short period of time. All patients were discharged
      after a mean of 17 days (range 7-38). Follow up with duplex scanning revealed
      that all grafts were patent. One patient developed a high grade anastomotic
      stenosis which was followed by recurrence of the symptoms. This was dilated on
      three occasions by balloon angioplasty within a period of 17 months. On the last
      occasion a stent was placed and since the patient remains asymptomatic.
      CONCLUSIONS: Antegrade visceral revascularisation via a thoracoabdominal approach
      is a durable and effective method of relieving symptoms of chronic visceral
      ischaemia. The low morbidity in this series justifies larger studies in order to
      establish the true incidence of complications.

PMID- 10071619
TI  - Experimental assessment of proximal stent-graft (InterVascular) fixation in human
      cadaveric infrarenal aortas.
AB  - OBJECTIVES: This paper investigates the radial deformation load of an aortic
      endoluminal prosthesis and determines the longitudinal load required to cause
      migration in a human cadaveric aorta of the endoprosthesis. DESIGN AND METHODS:
      The endovascular prosthesis under investigation was a 24 mm diameter, nitinol,
      self-expanding aortoaortic device (InterVascular, Clearwater, Florida, U.S.A.).
      Initially, a motorised digital force gauge developed an incremental load which
      was applied to the ends of five stent-grafts, to a maximum of 10 mm (42%)
      compression. Secondly, using a simple bench model, each ends of four stent-grafts
      were deployed into 10 cadaveric experimental aneurysm necks and a longitudinal
      load applied to effect distraction. RESULTS: Increasing load produced increasing
      percentage deformation of the stent-grafts. The mean longitudinal distraction
      load for an aneurysm neck of 20 mm was 409 g (200-480 g), for 15 mm was 277 g
      (130-410 g) and for 10 mm was 218 g (130-340 g). The aneurysm diameter and aortic
      calcification had p values of 0.002 and 0.047, respectively, while the p value
      for aneurysm neck length was less than 0.00001. CONCLUSIONS: These results
      suggest that there is a theoretical advantage of oversizing an aortic prosthesis
      and that sufficient anchorage is achieved in an aortic neck of 10 mm to prevent
      migration when fully deployed.

PMID- 10071620
TI  - Outcome of the first 100 femoropopliteal angioplasties performed in the operating
      theatre.
AB  - OBJECTIVES: To examine the factors influencing outcome and restenosis in an
      initial series of 100 infrainguinal angioplasties. DESIGN: Prospective study of
      angioplasties of the superficial femoral and popliteal arteries performed over a
      42-month period. MATERIALS AND METHODS: One hundred consecutive angioplasties in
      96 patients performed in the operating theatre between January 1993 and June 1996
      were followed prospectively with clinical, ABI, and duplex assessment. Forty-four
      procedures were for disabling claudication and 56 for critical ischaemia. Stents
      were deployed in 30 limbs. RESULTS: Angioplasty was successful in 84 of 100
      limbs. Cumulative patency of the entire group at 3, 6, 12 and 18 months was 78%,
      60%, 53%, and 49% respectively, while excluding initial failures, gave patencies
      of 95%, 69%, 63%, and 58%, respectively. Claudicants with a 1-year patency of 64%
      did significantly better than patients with critical ischaemia (44% p < 0.05).
      Angioplasties performed during the initial 21 months had a 1-year patency of 42%,
      while those performed in the final 21 months had a 74% patency (p = N.S.). The
      patency for stented arteries was 66% vs. 49% for angioplasty alone (p = N.S.).
      The 2-year limb salvage rate was 91% in patents with critical ischaemia. Forty
      six per cent of restenoses were asymptomatic. CONCLUSIONS: The results suggest
      that while angioplasty is useful in treating infrainguinal arterial disease,
      there is a learning curve, resulting in a high restenosis rate for occlusive and
      multilevel disease, while concomitant placement of stents may be beneficial.

PMID- 10071621
TI  - The surgical management of acute limb ischaemia due to native vessel occlusion.
AB  - OBJECTIVES: Data from the STILE study have indicated that for patients with
      subacute limb ischaemia due to native vessel occlusion, surgery is both more
      effective, and durable than thrombolysis. The purpose of this study was to
      evaluate the outcome of an aggressive surgical approach in patients presenting
      with acute limb-threatening ischaemia. DESIGN: Details of patients presenting
      with salvageable acute limb ischaemia due to native artery occlusion over a 6
      year period in a University hospital vascular unit setting were obtained from the
      vascular audit and the outcome of the surgical management of these patients was
      analysed. RESULTS: One hundred and seventy-four consecutive patients underwent
      surgery for acute native vessel limb ischaemia (76% lower, 24% upper limb).
      Fogarty thrombectomy or embolectomy was initially performed in 153 (89%)
      patients. Of these, 37 (24%) immediately underwent a further procedure: 28 (18%)
      had on-table thrombolysis and 14 (9%) underwent vascular reconstruction. Twenty
      six patients (15%) underwent further limb salvage surgery within 30 days. Life
      table analysis demonstrated a limb salvage rate of 88% and 76% at 30 days and 2
      years, respectively. Patient survival was 75% and 48% at the same time intervals.
      CONCLUSIONS: These results demonstrate that a role for aggressive surgical
      intervention still exists, resulting in high limb salvage rates.

PMID- 10071622
TI  - Relationship of femorodistal bypass patency to clinical outcome. Iloprost Bypass
      International Study Group.
AB  - OBJECTIVE: To investigate the relationship between bypass patency, limb survival
      and clinical symptoms after femorodistal bypass procedures. DESIGN: Multicentre,
      prospectively planned 12-month postoperative follow-up. PATIENTS AND METHODS:
      Five hundred and seventeen patients undergoing femorodistal bypass surgery for
      severe ischaemia. Clinical symptoms, bypass patency were recorded at regular
      intervals up to 12 months postoperatively. RESULTS: Complete follow-up data was
      obtained on 498 patients (96%). Fifty-six (17%) of the 341 patients with patent
      bypasses had either rest pain or ulcers or had undergone major amputation at 12
      months. Of the 167 patients with an occluded bypass, 22 patients (13%) had
      improved clinical symptoms and a total of 59 patients (35%) had avoided major
      amputation at 12 months. The clinical outcome for patients classified
      preoperatively as Fontaine stage IV was significantly worse than for those in
      stage III preoperatively despite similar bypass patency rates. CONCLUSIONS: There
      is a fair correlation between technical and clinical outcome after femorodistal
      bypass surgery at 12 months, but there are significant numbers of patients with
      occluded bypasses who have a good clinical outcome and of patients with patent
      bypasses who have a poor clinical outcome. The reporting of symptoms in addition
      to bypass patency would aid the interpretation of surgical results.

PMID- 10071623
TI  - Traumatic rupture of the aortic arch treated by stent grafting.

PMID- 10071624
TI  - Aorta--left renal vein fistula: an unusual complication of an abdominal aortic
      aneurysm.

PMID- 10071625
TI  - An unusual case of haematuria treated by endoluminal repair.

PMID- 10071626
TI  - [Risk of underestimating blood carbon monoxide by certain analytic methods].
AB  - OBJECTIVE: Study the effect of delay to assay on the measurement of
      carboxyhemoglobin (HbCO) in total blood samples. METHODS: Carbon monoxide (CO)
      and carboxyhemoglobin were measured on 75 blood samples drawn from healthy
      subjects (smokers and non smokers) and in subjects with carbon monoxide (CO)
      poisoning. Blood samples were drawn on lithium heparinate in perfectly closed
      tubes with no head space and stored at 4 infinity C until assay. The samples were
      pooled into 4 classes for 4 delays to assay: immediate, less than one hour, 3
      hours, 12 hours. Infrared spectrometry was used to assay CO and order 4 and 5
      derived spectrophotometry using CO-oximeters (AVL 912, IL 482, Corning 270,
      Radiometer OSM 3, Radiometer ABL 520) for HbCO. RESULTS: Regression lines for CO
      versus HbCO suggested that oxycarbonemia was underestimated using techniques
      measuring HbCO. This underestimation varied from 3 to 40% for delays to assay of
      0 to 3 hours. CONCLUSION: Clinicians should be aware that the underestimation in
      oxycarbonemia related to HbCO assays is sensitive to delay to assay.

PMID- 10071627
TI  - [Neurologic involvement in sarcoidosis. Federation of Systemic Diseases of
      Grenoble].
AB  - OBJECTIVE: Study the incidence, clinical features, prognosis and diagnostic and
      therapeutic strategies in neurological lesions of sarcoidosis. PATIENTS AND
      METHODS: The 207 cases of sarcoidosis followed at the Grenoble University
      Hospital between 1992 and 1998 were identified. After collecting data, the cases
      with neurological signs related to sarcoidosis were selected. RESULTS: Sixteen
      patients (7.7%) had neurosarcoidosis. Ten had central nervous system involvement,
      with 5 reaching the hypothalamus and pituitary glands, 2 cases of
      meningoencephalitis, 2 pseudotumoral lesions, and 1 bitemporal lesion. Six had
      peripheral nervous system involvement, 3 had facial palsies and 3 had
      neuropathies. Laboratory tests were not contributive to diagnosis. Ten magnetic
      resonance imaging series were pathological out of 11 performed. Three central
      nervous system biopsies were obtained. Corticosteroid therapy was the most
      frequent treatment. For hypothalamic and pituitary dysfunction, the only
      treatment was substitutive hormone therapy. The course was favorable in 11 cases,
      stable in 4 cases. Symptoms worsened despite treatment in only 1 case.
      CONCLUSION: The incidence of neurosarcoidosis may be much higher than is
      generally realized. The association of suggestive MRI signs, and clinical and
      laboratory findings evoke the diagnosis. Brain biopsy remains necessary for the
      pseudotumoral forms and the primitive neurological forms.

PMID- 10071628
TI  - [Severe air embolism after surgical irrigation with hydrogen peroxide].
AB  - BACKGROUND: Hydrogen peroxide is widely used for its antiseptic properties. In
      certain circumstances, however the risk of air embolism can create a life
      threatening situation. CASE REPORT: A 16-year-old adolescent required surgical
      treatment for femorotibial trauma. During the surgical procedure, cardiac arrest
      suddenly occurred when hydrogen peroxide was being used to irrigate the wound. A
      central catheter was inserted and aspiration of air bubbles in the line led to
      the diagnosis of air embolism. Outcome was unfavorable despite successful
      resuscitation. A chronic neurovegatative state ensued and the patient died 8
      months later. DISCUSSION: Several cases of air embolism have been described due
      to hydrogen peroxide in surgical, medical and accidental circumstances. Our case
      emphasizes the potential danger of using hydrogen peroxide in certain situations,
      including orthopedic surgery. Clinicians should be aware that hydrogen peroxide
      is not a perfectly safe product.

PMID- 10071629
TI  - [Autoimmune hepatitis: importance of budesonide in intolerance to prednisolone].

PMID- 10071630
TI  - [Endometrial cyst of the umbilicus].

PMID- 10071631
TI  - [Pregnancy, abortion and delivery in a cohort of heroin dependent patients
      treated with drug substitution (methadone and buprenorphine) in Aquitaine].

PMID- 10071632
TI  - [Why hospitalize stroke patients in a specialized unit?].
AB  - A PUBLIC HEALTH CHALLENGE: Cerebral vascular events are the third most frequent
      cause of death in the adult population and the number one cause of disabilities,
      a public health challenge both in terms of health care service and health care
      expenditures. SPECIALIZED UNITS: Structured health care facilities, particularly
      specialized hospital units, can lower mortality, limit residual disability and
      reduce the need for long-term institutionalization. OUTLOOK: Specialized research
      and teaching units are paradigmatic of the impact of health care organization.
      The limited number of such specialized units in France raises important ethical
      considerations about effective access to health care. Functioning units could be
      a useful criteria for auditing quality of hospital facilities.

PMID- 10071633
TI  - [7 reasons for hospitalizing stroke patients in special treatment units].
AB  - THE HELSINGBORG DECLARATION: One of the primary objectives of the Helsingborg
      declaration was that all patients should have access to care in a neurovascular
      unit. However to date, only a few specialized facilities are available in Europe.
      SEVEN GOOD REASONS: There are seven good reasons why patients suffering cerebral
      vascular events should be hospitalized in specialized care units. 1. Improve
      chances of survival and recovery: mortality at 3 and 12 months is 25% lower in
      patients hospitalized in specialized units and the combined risk of death and
      institutionalization is reduced by one-third. The beneficial effect in terms of
      survival and function persists at 5 years. 2. Provide optimal management for
      emergency conditions which may be confounded with cerebral vascular events and
      which require emergency care. 3. Optimize health care organization. 4. Favor
      research and teaching. 5. Reduce health expenditures related to cerebral vascular
      events. 6. Inform health authorities of the needs of this population. 7. Prepare
      for the possible development of intravenous thrombolytic therapies. OUTDATED
      ATTITUDE: Fatalism and nihilism is no longer an acceptable attitude. Cerebral
      vascular events must be considered as an emergency condition and our health care
      system must change, adapting health care facilities to this new situation.
      Neurovascular units provide one of the most effective tools to meet this
      challenge.

PMID- 10071634
TI  - [Postoperative patient management. Perioperative myocardial infarct].
AB  - A FREQUENT AND SEVERE EVENT: The incidence and the pathogenic mechanisms of
      cardiac complications in general surgery patients are now well described. Acute
      myocardial necrosis, the most frequent complication, is observed in 3 to 5% of
      patients at risk. Most are silent subendocardial lesions, but may have a short
      term or mid-term life-threatening effect in these surgery patients. EARLY
      POSTOPERATIVE PERIOD: In most patients, cardiac events occur within 48 hours of
      surgery. Diagnosis is confirmed by elevated troponin I. The immediate
      postoperative period is characterized by increased left ventricular load and
      metabolic disturbances, increased release of catecholinergic mediators and
      hypercoagulability, factors related to the effect of anesthesia on circulation
      and surgical stimuli. These modifications compromise the energy balance in the
      myocardium and favor the development of left ventricular failure. ECG RECORDINGS:
      Continuous recordings in the postoperative period have shown that although the
      number of episodes of myocardial ischemia is not affected during surgery, their
      number doubles during the postoperative period, a factor predicting postoperative
      infarction. OPTIMAL CARE: Cardiovascular and anti-aggregate therapy should be
      adapted in patients with an underlying heart or coronary condition. Postoperative
      circulatory load and hyperaggregability should be controlled. This involves
      preventing hypothermia, intensive analgesia and, in some cases, cardiovascular
      therapy using beta blockers or alpha 2 agonists.

PMID- 10071635
TI  - [Postoperative management. Critical care in intra-abdominal infection after
      surgical intervention].
AB  - UNDERESTIMATED FREQUENCY: Post-operative intraabdominal infections usually appear
      as abscesses or injury of the bowel, either alone or in combination. These
      complications of frequently underestimated frequency are characterized by high
      mortality. Improvement of their prognosis is obtained by early recognition of the
      complication and a multidisciplinary approach. ALARM SIGNS: In a patient who
      recently underwent abdominal surgery, the onset of abnormal signs must be
      considered as an alarm which imposes ruling out intraabdominal complications.
      Unexplained multiple organ failure or septic shock in the post-operative period
      of intraabdominal surgery must lead to considering explorative laparotomy.
      THERAPEUTICS: Etiologic treatment must be ideal and total from the first
      reoperation. Antibiotic therapy administered from the surgical reoperation must
      be different from previous treatments. This treatment is aimed at eradicating
      enterobacteriaceae, non-fermenting Gram negative aerobes, Gram positive cocci,
      anaerobes and fungi.

PMID- 10071636
TI  - [Postoperative patient management. Pain after surgical intervention].
AB  - A MAJOR CHALLENGE: Management of post-operative pain is insufficient. One out of
      2 patients suffers intense or very intense pain during the first days after
      surgery. The inefficacy of analgesic therapy is related to lack of a sufficiently
      organized pain-relief protocol. Patients are insufficiently informed,
      prescriptions lack precision, postoperative pain is not regularly evaluated, and
      patient controlled analgesia (PCA) and loco-regional techniques are
      insufficiently applied. NECESSARY STEPS: Pain relief protocols in surgery units
      should be organized in a stepwise fashion. The first step is to record the
      patient's level of pain every 8 hours during the first 5 days after surgery. The
      second step is to define the role of each health carer in the implementation of
      analgesic techniques. The third step is to develop adapted analgesic techniques
      (paracetamol and anti-inflammatory drugs, subcutaneous morphine, PCA and loco
      regional techniques, particularly peripheral blocks for orthopedic surgery). The
      final step is an evaluation phase aimed at assessing the impact on the management
      of postoperative pain in the unit. LOW COST: Optimally, the entire procedure,
      integrated into an overall quality assurance program, is directed by one
      reference physician assisted by a nurse specially qualified in pain relief. The
      overall financial burden, including drug costs, material and health care
      personnel is minimal. In French units, it has been estimated at around 10 to 20 F
      per patient per day.

PMID- 10071637
TI  - [Responsibility of the radiologist in bone radiology].

PMID- 10071638
TI  - [Rights and responsibilities of the radiologist in determining indications and
      applying radiologic procedures].
AB  - A radiological examination or an interventional procedure is a medical invasion
      of the patient's freedom and does not constitute an offense of causing bodily
      harm there is a medical indication, when the patient has given consent after
      being adequately informed, and the intervention is carried out in accord with the
      valid rules of medical conduct. During the assessment of possible
      contraindications, the radiologist must also evaluate the indicationy, i.e., he
      or she must decide if the medical question can be answered by the requested
      radiological examination. The indication must be viewed the more critically the
      greater the risk for a complication is. A radiological diagnosis with the use of
      X-rays may only be employed when it will furnish information with therapeutic
      consequences. The more urgent the indication, the less strict are the
      requirements for informed consent and agreement, and vice versa. Thus, the
      information need for a purely diagnostic procedure without any direct therapeutic
      value is particularly high. The consent of the patient is only legally binding
      when he has been informed in advance of the objectives, extent, necessity and
      urgency, type, procedures, and alternatives of a medical investigation or
      therapeutic intervention and also of the accompanying risks. All risks on the
      basis of which a responsible patient can make the decision to consent or to
      reject a specific medical intervention are to be considered as relevant and must
      be explained appropriately.

PMID- 10071639
TI  - [Occult fractures of the wrist joint: high resolution image magnification
      roentgen versus MRI].
AB  - PURPOSE: To compare the diagnostic value of high definition macroradiography and
      MRI in patients with the suspicion of occult wrist fractures. MATERIALS AND
      METHODS: In a prospective study, 23 patients with clinically suspected wrist
      fractures and normal initial plain radiographs underwent high resolution
      macroradiography and MR imaging shortly after trauma. Macroradiographs were taken
      with a microfocus tube using an anode of 0.03-0.3 mm providing a 4x magnification
      of the wrist, which was obtained in 4 projections. MR images were performed on a
      1.0 T MR unit in coronal planes using T1 weighted SE, T2.-weighted 3D GE, and
      Turbo-STIR sequences. Follow-up radiographs after 6 weeks were used to confirm
      the diagnosis of a primary occult wrist fracture. RESULTS: Macroradiography
      depicted 5 wrist fractures: 4 fractures of the scaphoid bone and 1 fracture of
      the capitate bone. MRI demonstrated 11 fractures (one of them false-positive): 9
      fractures of the scaphoid bone and two fractures of the capitate bone. Using
      macroradiography, the sensitivity for the detection of occult fractures of the
      wrist was 50% with a specificity of 100%, using MRI the sensitivity was 100% with
      a specificity of 92%. CONCLUSION: MRI seems to be superior to high resolution
      macroradiography in the detection of occult scaphoid fractures and thus is
      recommended in the management of patients with clinically suspected scaphoid
      fractures not evident on initial plain films.

PMID- 10071640
TI  - [Kinematic versus static MRI study of the cervical spine in patients with
      rheumatoid arthritis].
AB  - PURPOSE: The objective of this study was to compare the diagnostic value of
      cinematic magnetic resonance imaging with static MRI examinations in patients
      with rheumatoid arthritis and concomitant attack of the cervical spine. METHODS:
      Dynamic functional MRI examinations of the cervical spine were performed one five
      subjects without complaints and 20 patients with rheumatoid arthritis. For the
      functional studies, a positioning frame was used that allowed infinitely variable
      forward and backward inclinations of the head. RESULTS: Functional magnetic
      resonance imaging made possible a sufficiently good differentiation of the
      extension of pannus tissue cranial, ventral, and dorsal of the dens with possible
      displacing and impinging effects on the spinal cord during flexing and stretching
      movements. In addition, it is suitable for demonstration of the degree of
      instability in the atlanto-occipital and atlanto-axial planes. In contrast to
      conventional X-rays, CT, and static MRI, basilary impression as well as
      compressions and angulations of the cervical bone marrow are better visualized by
      cinematic magnetic resonance tomography. CONCLUSIONS: Functional magnetic
      resonance tomography is an important diagnostic method for the induction of the
      cervical spine in patients with rheumatoid arthritis. In particular, fusion and
      instabilities as well as compressions of the bone marrow often can only be
      detected with the help of functional MRI.

PMID- 10071641
TI  - [MRI diagnosis in longitudinal stress fractures: differential diagnosis of Ewing
      sarcoma].
AB  - PURPOSE: To compare MR imaging features of stress fractures, simulating
      malignancies, and Ewing sarcomas. MATERIALS AND METHODS: MR imaging studies of 4
      patients with longitudinal stress fractures of the tibia (n = 2) and the femur (n
      = 2) simulating malignancy were retrospectively compared with the MRI scans of 10
      patients with histologically proven Ewing sarcoma (femur n = 5; tibia n = 3,
      fibula n = 1, humerus n = 1). The diagnosis of stress fractures was confirmed by
      follow-up examinations. An additional biopsy was performed in two patients.
      RESULTS: Despite negative x-ray examinations, MRI showed the fracture line in all
      patients with stress fractures. In these cases marrow edema was irregular and
      there was no well defined margin towards normal fatty marrow. In contrast Ewing
      sarcomas were sharply demarcated in 9/10 cases. Extraosseous enhancing soft
      tissue was found in Ewing sarcomas as well as in stress fractures. In stress
      fractures the enhancing mass was repair tissue. Areas of necrosis within the
      enhancing mass was seen in (8/10) Ewing sarcomas, only. In follow-up studies we
      observed a decrease of the marrow edema in patients with stress fractures.
      Occurrence of low signal areas in T1- and T2-weighted sequences within the
      initial enhanced extraosseous tissue corresponded to bony callus on x-rays films.
      CONCLUSIONS: Repair tissue in stress fractures can imitate malignancy. The
      irregularity of the marrow edema without well defined margins, the lack of
      necrosis in the small enhancing tissue and the proof of the fracture line in the
      MRI are criteria to differentiate stress fractures from Ewing sarcomas. Short
      term follow up studies are helpful to underline the diagnosis.

PMID- 10071642
TI  - [Low-field MRI of the knee joint: results of a prospective, arthroscopically
      controlled study].
AB  - PURPOSE: To define the diagnostic accuracy of an open low-field MR unit (Magnetom
      Open, Siemens, Erlangen) in traumatic knee lesions. MATERIALS AND METHODS: The
      MRIs of 150 patients were prospectively evaluated by two independent readers with
      different experience levels. The study protocol included a proton-density
      weighted SE-sequence in the sagittal, a T2.-weighted Flash-2D-sequence in the
      coronal, and a 3D-acquisition (DESS) in the axial plane. 75 patients were treated
      either conservatively or operatively. RESULTS: Based on arthroscopy as the gold
      standard, the sensitivities, specificities, and diagnostic accuracies for lesions
      of the medial and lateral meniscus, the anterior cruciate ligament (ACL), the
      hyaline cartilage, and the posterior cruciate ligament (PCL) were 92%, 92% and
      92%, 83%, 93% and 92%, 95%, 96% and 96%, 74%, 93% and 85%, and 100%,
      respectively, for reader 1. The values for reader 2 were 81%, 74% and 77% (medial
      meniscus), 61%, 86% and 80% (lateral meniscus), 79%, 95% and 91% (ACL), 48%, 91%
      and 73% (hyaline cartilage), and 100% each (PCL), respectively. There were no
      statistical differences between the two readers (Fisher's Exact Test, 95%
      confidence interval). CONCLUSIONS: Using a time-consuming examination protocol,
      the diagnostic accuracies of the open low-field MR unit are well comparable to
      those obtained with mid- or high-field units. Although not statistically
      significant in this study, the experience level of the examiner seems to be of
      considerable clinical relevance.

PMID- 10071643
TI  - [MRI of plantar fasciitis].
AB  - PURPOSE: The purpose of this study was to determine the type and frequency of
      characteristic bone and soft tissue changes on MRI of patients with a clinical
      diagnosis of plantar fasciitis. MATERIALS AND METHODS: 28 patients with a
      clinical diagnosis of plantar fasciitis underwent MR imaging. Besides T1- and T2
      weighted sequences, short-tau-inversion-recovery sequences were used routinely.
      In 27 patients T1-weighted images after intravenous contrast injection were
      acquired additionally. As a control group the images of 15 patients without
      clinical signs for plantar fasciitis were evaluated. RESULTS: In 25 of 28 cases
      (89%) the clinical diagnosis of plantar fasciitis was established by MR imaging.
      The most common finding was a peritendinous edema at the calcaneal insertion site
      which was found in all 25 patients. In 19 of 25 cases (76%) a bone marrow edema
      of the calcaneus was present. In 14 of 25 cases (56%) an intratendinous signal
      intensity increase of the plantar fascia could be observed which showed contrast
      enhancement in 12 cases. Compared to the control group (mean thickness 3.3 mm)
      the plantar fascia showed significant thickening in the 25 MR positive patients
      (mean thickness 6.72 mm). DISCUSSION: Besides thickening of the plantar fascia
      and intratendinous signal intensity increase with contrast enhancement to some
      extent, bone marrow edema of the calcaneus and peritendinous edema close to the
      plantar fascia are characteristic signs of plantar fasciitis on MRI. Both signs
      can reliably be seen on STIR sequences only.

PMID- 10071644
TI  - [Cardiac MRI for determining functional left ventricular parameters].
AB  - PURPOSE: To prove the accuracy of MR methods in the determination of left
      ventricular (LV) functional parameters and anatomy. MATERIALS AND METHODS: At 1.5
      T, 20 healthy volunteers and 22 patients with aortic valvular disease (stenosis n
      = 15, regurgitation n = 7) were examined. Functional parameters like cardiac
      output, ejection fraction, end-diastolic volume, aortic flow maximum, and time
      interval from the R-wave to maximum flow were obtained using a velocity encoding
      2D FLASH sequence (TR 24 ms, TE 5 ms, venc 250 cm/sec) and segmented breath-hold
      cine FLASH 2D technique (TR 100 ms, TE 4.8 ms, flip angle 25 degrees, temporal
      resolution 50 ms). Invasive measurements (Fick principle) served as gold
      standard, intra- and interobserver variability were determined. RESULTS:
      Differences of functional parameters between normal volunteers and patients were
      detectable at a high level of significance (p < 0.0001). For cardiac output a
      superior correlation with the gold standard was found using flow measurements (r
      = 0.66, p < 0.0007) compared to volumetric calculations from cine studies (r =
      0.47, p < 0.02). Interobserver variability was 2.5 +/- 2.7%/4.5 +/- 6.9% (flow
      quantification/calculations from cine studies), intraobserver variability was 1.7
      +/- 1.6%/3.3 +/- 2.2%. CONCLUSIONS: MRI is an appropriate tool for determining LV
      functional parameters and anatomy. Differences between normal volunteers and
      patients with aortic valvular disease can be detected reliably. Flow measurements
      turned out to be more accurate than calculations from cine images. Therefore,
      flow quantification techniques should be preferred for clinical use.

PMID- 10071645
TI  - [Accuracy of right and left ventricular heart volume and left ventricular muscle
      mass determination with cine MRI in breath holding technique].
AB  - PURPOSE: To assess the accuracy of right- (RV) and left-ventricular (LV) heart
      volume and muscle mass determinations by cine MR imaging. MATERIALS AND METHODS:
      Ten subjects were examined twice by a segmented, ECG-triggered cine sequence in
      the short axis plane and breath-hold technique by two independent operators and
      again 4 weeks later by one of the operators. The contours were evaluated manually
      by two independent examiners and again four weeks later by one of the examiners.
      LV and RV end-diastolic and end-systolic volumes, stroke volume, cardiac output,
      ejection fraction (EF), and left-ventricular muscle mass were compared. RESULTS:
      The RV evaluation variations (RV-EF: 6.46%) were higher than the LV (LV-EF:
      4.46%). The intra-examiner variations were smaller than the inter-examiner
      variations. The generally operators did not cause a significantly increased
      variation (LV-EF: 5.77%). In contrast, the repeat examinations at different times
      did lead to a significant increase in the variation (LV-EF: 10.15%). CONCLUSIONS:
      The rapid ECG-triggered cine MRI in breath-hold technique allows the simultaneous
      RV and LV, artefact-free determination of heart volumes and LV muscle mass. The
      LV volumes can be determined more accurately than the RV. The examiner has a
      distinct influence on the accuracy, the operator has a lesser effect.
      Physiological fluctuations of cardiac activity significantly influence the follow
      up.

PMID- 10071646
TI  - [Retroperitoneal recurrence of non-seminomatous testicular tumors: computerized
      tomography findings before retroperitoneal lymph node excision].
AB  - PURPOSE: In relapsing testicular cancer, additional chemotherapy is followed by
      abdominal CT. If residual lesions are found, retroperitoneal lymphadenectomy is
      considered. We studied retrospectively whether morphological criteria can help in
      selected cases in deciding about lymphadenectomy by distinguishing between vital
      tumor, scarring and mature teratoma. METHODS: In 26 patients who had been treated
      by salvage chemotherapy and retroperitoneal lymphadenectomy for non-seminomatous
      testicular cancer between 1990 and 1997, abdominal computed tomography and
      histology were correlated. RESULTS: Histological examination found scarring in 10
      patients, vital tumor in 6, mature teratoma in 4, and simultaneous teratoma and
      vital tumor in 6. A single CT criterion for distinguishing between these
      histologies was not identified. In two patients with large masses which were
      partly cystic and partly solid vital tumor and teratoma were verified. Scarrings
      may be expected in cystic lesions at the level of the renal hilus which are lined
      by a thin and smooth wall. Size did not matter. CONCLUSION: Accurate
      differentiation between vital tumor and necrosis was not possible. Before
      lymphadenectomy CT, however, localised lesions.

PMID- 10071647
TI  - [Digital flat image detector technique based on cesium iodide and amorphous
      silicon: experimental studies and initial clinical results].
AB  - PURPOSE: Experimental and clinical evaluation of a digital flat-panel X-ray
      system based on cesium iodide (CsI) and amorphous silicon (a-Si). METHODS:
      Performance of a prototype detector was compared with conventional screen-film
      radiography (SFR) using several phantom studies. Foreign bodies, fractures,
      osteolyses, and pulmonary lesions were analyzed. Additionally, 120 patients were
      studied prospectively, resulting in 400 comparative X-ray studies. The flat-panel
      detector was exposed with standard dose and with a dose reduction of up to 75%.
      Detector size was 15 x 15 cm, pixel matrix was 1 x 1 k with a pixel size of 143
      microns. Modulation-transfer function was determined to be 18% at the maximum
      spatial resolution of 3.5 lp/mm. RESULTS: The diagnostic results achieved with
      the digital detector were similar to those of conventional SFR, even at reduced
      radiation exposure. A potential for dose reduction was observed: 50% with respect
      to osteoarthrosis and fractures, and 75% for determining bony alignment.
      DISCUSSION: This new technology can be used in thoracic and skeletal radiography.
      A significant dose reduction is possible, depending on the suspected disease.

PMID- 10071648
TI  - [Benefits, costs and analysis in diagnostic radiology: definitions and glossary].
AB  - Cost efficiency analyses in clinical radiology require the application of methods
      and techniques that are not yet part of the academic qualifications of the
      specialists. The procedures used are borrowed from economics, decision theory,
      applied social sciences, epidemiology and statistics. Many expressions hail from
      the angloamerican literature and are presently not yet germanized unequivocally.
      This survey is intended to present main terms of cost efficiency analysis in the
      english version as well as a german translation, to give a clear definition and,
      if necessary, explanatory notes, and to illustrate their application by means of
      concrete radiologic examples. The selection of the terms is based on the
      hierarchical models of health technology assessment resp. clinical outcome
      research by Fryback & Thornbury resp. Maisey & Hutton. In concrete terms, both
      the differences between benefit, outcomes, and utility and the differences
      between effectiveness, efficacy and efficiency and the differences between
      direct, indirect, intangible, and marginal costs are explained. True cost
      efficiency analysis is compared with cost effectiveness analysis, cost
      identification analysis, cost minimization analysis, and cost utility analysis.
      Applied social sciences are represented by the Medical Outcomes Study Short Form
      36 and the QALY conception. From decision theory both the analysis of
      hypothetical alternatives and the Markov model are taken. Finally, sensitivity
      analysis and the procedures of combined statistical evaluation of comparable
      results (meta-analysis) are quoted.

PMID- 10071649
TI  - [Temporary balloon occlusion as therapy of uncontrollable arterial hemorrhage in
      multiple trauma patients].
AB  - PURPOSE: Presentation of temporary balloon occlusion as an interventional
      radiological method for managing hemorrhage in multiply injured patients with
      uncontrollable loss of blood. METHOD: Temporary, non-selective arterial occlusion
      by introduction of a balloon catheter contralaterally to the source of bleeding
      has been performed since 1992 on 7 patients with multiple injuries, hemorrhagic
      shock requiring reanimation, and angiographic demonstration of an arterial
      hemorrhage in the supply region of the internal iliac artery with complex pelvic
      fracture. In each case a PTA balloon catheter was introduced transfemorally, non
      selectively positioned proximal to the bleeding source, and left in place for 24
      48 h under manometric control. Control angiographies were performed prior to
      catheter removal. RESULTS: The bleeding was stopped immediately in all 7
      patients. The hemodynamic stability made transport and thus further surgical
      management and/or a short-term treatment in the intensive-care station possible.
      Control angiographies confirmed that the bleeding had stopped in all patients.
      CONCLUSIONS: We recommend temporary balloon occlusion as a rapid and effective
      method for the management of bleeding in otherwise uncontrollable traumatic
      hemorrhages in the supply region of the internal iliac artery.

PMID- 10071650
TI  - [Dose-dependent decrease of the rate of restenosis of stents in peripheral
      vessels with reviparin].
AB  - PURPOSE: In clinical prospective trials, we examined the effect of the low
      molecular weight heparin (lmwh) reviparin on restenosis rate after Strecker stent
      implantation in femoral popliteal arteries. MATERIALS AND METHODS: 62 patients
      were treated between 1992 and 1998. Patients received reviparin, 3500 IU, prior
      to stent implantation followed by 7500 IU for 24 h (i.v.) and 2 x 1750 IU/day
      s.c. over three weeks (n = 12) or 10,500 IU for 24 h (i.v.) and 2 x 3500 IU/day
      s.c. over 3 1/2 weeks (n = 50). Follow-up parameters were clinical symptoms,
      ankle-brachial index, color Doppler flow duplex sonography, and DSA. RESULTS:
      Three thrombotic occlusions and three stenoses were observed in the low-dose
      group. Raising the dose resulted in neither thrombotic nor other events within
      the first three months. Seven stenoses occurred afterwards up to the 7th month.
      The complication rate was low: one moderate hematoma and one puncture aneurysm.
      Primary patency rate was 88% and 80% for one and two years, respectively. This is
      significantly better than the primary patency rates for patients receiving low
      dose lmwh (p < 0.005) or unfractionated heparin (p < 0.05). CONCLUSIONS: Hence,
      high-dose administration of the lmwh reviparin lowers the restenosis rate after
      stent implantation in femoropopliteal arteries.

PMID- 10071651
TI  - [Optimization of numerical measurement parameters for ECG-triggered MRI snapshot
      FLASH myocardial perfusion studies].
AB  - BACKGROUND AND AIMS: In MR examinations of myocardial perfusion by the use of
      Snapshot-FLASH sequences it is of major importance that the achievable signal
      difference between pre- and normal postcontrast myocardium be maximized. METHODS:
      In ECG-triggered Snapshot-FLASH sequences the signal intensity of the myocardium
      depends on the flip angle alpha, the inversion time TI and the trigger delay TD
      (both depending on the cardiac frequency f) for unchanged slice thickness (SL),
      matrix size (MA), repetition time (TR) and echo time (TE). Therefore a simulation
      of the signal behavior of pre- and postcontrast myocardium based on Bloch's
      equations was performed by varying the flip angle alpha, TI and TD for different
      cardiac frequencies in order to determine an optimized combination of the
      measurement parameters. RESULTS: In normal heart rates (50-70 beats/min) maximal
      signal differences between pre- and normal postcontrast myocardium can be reached
      for inversion times TI = 170-200 ms and a flip angle alpha = 11 degrees. For
      higher heart rates again alpha = 11 degrees and TI = 200-220 ms with shortened TD
      (TD = 0 for f > 90 beats/min) were found to be optimal. The calculated values
      were semiquantitatively confirmed in phantom and volunteer measurements.
      CONCLUSIONS: The described method allows cardiac frequency dependent optimization
      of the Snapshot-FLASH measurement parameters alpha, TI and TD in order to reach a
      maximum in signal contrast between normal and malperfused myocardium.

PMID- 10071652
TI  - [In vitro comparison of a size 6F and 8F high-speed rotational catheter for
      mechanical thrombus fragmentation].
AB  - PURPOSE: In vitro comparison of the 6F and 8F Amplatz thrombectomy device (ATD)
      for treatment of thrombotically occluded vessels in a flow-model. MATERIALS AND
      METHODS: Thrombectomy of clots from porcine blood was performed with either a 6F
      or an 8F Amplatz thrombectomy device (ATD) in a flow-model simulating a
      superficial femoral artery circuit (n = 40; 7.5 g: 7 mm diameter; 4.5 g: 5 mm
      diameter). Emboli caused during thrombectomy were determined in a three-step
      filter array (10 microns-1000 microns). RESULTS: Thrombectomy was successful in
      all cases. In 5 mm/7 mm lumen time for thrombectomy was measured from 47 s/56s
      (8F) to 86 s/107 s (p < 0.01) (6F). Remaining thrombus weighted in 5 mm/7 mm
      lumen 0.04 g/-0.02 g (8F) and 0.05 g/-0.02 g (6F). Overall weight emboli
      determined for 1000 microns, 100 microns and 10 microns size and percentage of
      emboli related to original thrombus weight measured 0.23 g/4.96% (8F, 5 mm), 0.2
      g/4.36% (6F, 5 mm), 0.08 g/1.13% (8F, 7 mm). and 0.09 g/1.18% (6F, 7 mm).
      CONCLUSIONS: In vitro, the 6F ATD is in "vessels" with 5 mm and 7 mm diameter as
      effective as the 8F version. Particle embolization in flow-circuit was similar
      with both devices, although the 6F ATD requires a longer time for thrombectomy in
      vessel with larger diameter.

PMID- 10071653
TI  - [Assessment of the effective dose for routine protocols in conventional CT,
      electron beam CT and coronary angiography].
AB  - PURPOSE: To compare the effective dose applied by sequential CT (SEQ), spiral CT
      (SCT), electron beam CT (EBT) and coronary angiography for investigations of the
      chest, abdomen and the heart. METHODS: The Alderson Phantom was used to compare
      the effective dose for all modalities. In addition, the effective dose for
      conventional CT (SEQ and SCT) was estimated with a mathematical phantom. RESULTS:
      For CT investigation of the chest and abdomen the dose was highest for the EBT
      (11 mSv and 25 mSv, respectively) and slightly lower for the SEQ (7.8 mSv and
      21.5 mSv, respectively), whereas spiral CT required the least dose (5.3 mSv and
      8.8 mSv, respectively). For coronary calcium screening (0.8 mSv) and EBT coronary
      angiography (1.7 mSv) the dose was lower than for coronary catheter angiography
      (3.3 mSv). For conventional CT the difference between the effective dose derived
      by the mathematical phantom and by the Alderson phantom was 2% to 20%.
      CONCLUSIONS: For investigations of the chest and abdomen the effective dose
      applied by SCT is significantly lower than that with EBT and SEQ. For
      investigation of the coronary arteries the effective dose applied by EBT is lower
      than that for coronary catheter angiography.

PMID- 10071654
TI  - [PTLA (percutaneous transluminal laser angioplasty) recanalization of femoral
      artery stenoses/occlusions after Angio-Seal administration].
AB  - PURPOSE: To demonstrate desobliration of Angio-Seal-induced femoral artery
      stenosis and occlusion by Excimer-laser assisted angioplasty and PTA. PATIENTS
      AND METHODS: The Angio-Seal hemostatic closure device was applied to the puncture
      site in 1500 patients after diagnostic or therapeutic coronary artery
      catheterisation. In 5 of 1500 cases symptoms of claudication occurred. Following
      the determination of the walking distance and ankle-brachial systolic pressure
      index (ABI) and diagnostic angiography, therapeutic percutaneous transluminal
      laser angioplasty (PTLA) and PTA was performed. RESULTS: 5 patients with acute
      symptoms of peripheral artery disease presented with superficial femoral artery
      occlusions (three cases) and high grade stenoses of the common femoral arteries
      (two cases). Angiographic and clinical improvement was achieved after PTLA/PTA in
      all five patients. The mean walking distance increased from 61 meters to 600
      meters. The average ankle-brachial systolic pressure index increased from 0.40 to
      0.82. CONCLUSIONS: PTLA/PTA is a satisfactory therapeutic method for femoral
      artery occlusion or high-grade stenosis following Angio-Seal application.

PMID- 10071655
TI  - [Color-coded volume reconstruction for 3-dimensional presentation of CT data].
AB  - PURPOSE: To evaluate a technique of colored three-dimensional reconstructions
      without segmentation. MATERIAL AND METHODS: Color-coded volume rendered images
      were reconstructed from the volume data of 25 thoracic, abdominal,
      musculoskeletal, and vascular helical CT scans using commercial software. The CT
      volume rendered voxels were encoded with color in the following manner. Opacity,
      hue, lightness, and chroma were assigned to each of four classes defined by CT
      number. Color-coded reconstructions were compared to the corresponding grey-scale
      coded reconstructions. RESULTS: Color coded volume rendering enabled realistic
      visualisation of pathologic findings when there was sufficient difference in CT
      density. Segmentation was necessary in some cases to demonstrate small details in
      a complex volume. CONCLUSION: Color coded volume rendering allowed lifelike
      visualisation of CT volumes without the need of segmentation in most cases.

PMID- 10071656
TI  - [Sarcoma of the pulmonary artery--pre- and postoperative radiologic findings in
      initial tumor manifestation and recurrence].
AB  - PURPOSE: Primary pulmonary artery sarcomas are very rare tumors. Their diagnosis
      is difficult due to their unspecific symptoms. Still, an early preoperative
      diagnosis is the only possibility for a potential therapy. PATIENTS AND METHODS:
      4 pre- and 5 postoperative CT- and three pre- and one postoperative MRT
      examination(s) have been evaluated with respect to surgical and histological
      findings. RESULTS: The presence of a convex intraluminal bulging mass spreading
      mostly from the pulmonary trunc continuously into the peripheral pulmonary artery
      branches the filling and dilatation of the vessels, the tumor's inhomogeneity
      indicating hemorrhages and necrosis and the appearance of intrapulmonary nodules
      are found in both CT and MRI. Recurrent pulmonary artery sarcoma features an
      extravascular growth and is similar to lung cancer affecting the vessels. It
      shows contrast enhancement both in CT and MRI while the primary tumor shows a
      distinct contrast enhancement only of Gadopentetate dimeglumine but none or
      little enhancement in CT. CONCLUSION: The criteria presented in knowledge of CT
      and MRI serve to increase the probability for a correct preoperative diagnosis
      and thus allow adequate surgical planning.

PMID- 10071657
TI  - [Fibromuscular dysplasia of the brachial artery--2 case reports and review of the
      literature].
AB  - Yet being an uncommon disease in general, the manifestation of the fibromuscular
      dysplasia (FMD) in the upper extremities is exceedingly rare. Two patients with
      FMD of the brachial artery are presented and the literature concerned is
      reviewed. In this location the formation of microthrombi with subsequent
      embolization into the periphery instead of progressive vessel stenosis seems to
      be the leading pathophysiological principle. Therapeutic options are discussed.

PMID- 10071658
TI  - [Diagnosis and therapy of bronchial artery aneurysm].

PMID- 10071659
TI  - [Unusual pulmonary involvement in Wegener disease].

PMID- 10071660
TI  - [Transbiliary jejunal catheter for enteral feeding].

PMID- 10071661
TI  - [Mammography: bilateral calcified pseudotumor of the breast after cadaver fatty
      tissue implantation].

PMID- 10071662
TI  - Antiemetics.
AB  - The development of specific receptor antagonists, especially dopamine and
      serotonin, has broadened and strengthened the options available for the treatment
      of nausea and vomiting. In addition to the availability of these specific
      receptor antagonists, the use of combination regimens has become a major
      improvement in the ability to reduce side effects of many treatment protocols.

PMID- 10071663
TI  - Assessment of orthostatic blood pressure: measurement technique and clinical
      applications.
AB  - BACKGROUND: Orthostatic hypotension, a decline in erect blood pressure, is the
      result of an impaired hemodynamic response to an upright posture or a depletion
      intravascular volume. The measurement of orthostatic blood pressure can be done
      at the bedside and therefore is easily applied to several clinical disorders.
      Despite its usefulness, the measurement is often neglected, possibly because of
      confusion regarding the appropriate measurement technique and suitable
      application to patient care. METHODS: Pertinent recent medical literature was
      reviewed. RESULTS: The normal physiologic response to the assumption of an
      upright posture is a small drop in blood pressure and a slight rise in pulse
      rate. Orthostatic hypotension is detected by measurement of blood pressure in two
      or more body positions. An abnormal blood pressure response can be observed with
      disorders such as syncope, falling, intravascular volume depletion, and autonomic
      dysfunction; with the treatment of maladies such as hypertension and heart
      failure; and with the use of several medications. CONCLUSIONS: The measurement of
      orthostatic blood pressure is an essential clinical tool for the assessment and
      management of patients affected by common medical disorders.

PMID- 10071664
TI  - Appalachian perspective on modifiable risk factors in coronary artery disease:
      how well are we doing?
AB  - BACKGROUND: Despite recognition of modifiable risk factors and available and
      effective life-style and pharmacologic therapies, many individuals have
      unrecognized or untreated risk factors for coronary artery disease. METHODS:
      Using MEDLINE, we searched for relevant review articles and clinical trials
      related to hypertension, hyperlipidemia, diabetes mellitus, smoking, physical
      activity, obesity, and psychologic risk factors for coronary artery disease. We
      carefully reviewed the literature and statistics on modifiable risk factors and
      identified appropriate physician interventions. RESULTS: A large amount of
      information is available on coronary artery disease and modifiable risk factors.
      Much of the data focuses on diagnosis and treatment to goal. CONCLUSIONS:
      Coronary artery disease remains the number one cause of death in the United
      States and West Virginia, even though specific guidelines have been established
      for detection and treatment. The medical community needs to be more aggressive in
      managing modifiable risk factors.

PMID- 10071665
TI  - Chalk eating in middle Georgia: a culture-bound syndrome of pica?
AB  - BACKGROUND: Although geophagia (earth eating) has been observed and documented in
      many areas of the world, the specific preference for consuming kaolin is less
      well known. The ingestion of kaolin, also known as white dirt, chalk, or white
      clay, is a relatively common type of pica found in the central Georgia Piedmont
      area. METHODS: We reviewed the literature, made informal contacts with Georgia
      physicians, and arranged semistructured interviews with 21 individuals with a
      history of chalk eating; we gathered both quantitative and qualitative
      information. RESULTS: Kaolin ingestion appears to be a culturally-transmitted
      form of pica, not selectively associated with other psychopathology. CONCLUSION:
      Kaolin ingestion appears to meet the DSM-IV criteria for a "culture-bound
      syndrome."

PMID- 10071666
TI  - Sledding injuries in the southeastern United States.
AB  - BACKGROUND: Heavy ice and snow accumulation combined with record low temperatures
      in Chattanooga, Tennessee, from February 2-6, 1996, contributed to many sledding
      injuries. METHODS: We retrospectively reviewed medical records of emergency
      visits to seven area hospitals from February 2-6, 1996. We further reviewed
      sledding injury records. Sledding was defined as sliding on snow or ice using any
      device except skis. RESULTS: Of 2,134 emergency room visits, 241 patients had 310
      sledding injuries. Ages of patients ranged from 3 to 53 years (mean, 18.9;
      median, 16). One hundred twenty-eight injuries were severe. These included
      extremity injuries (65), head injuries (28), chest injuries (10), intra-abdominal
      injuries (10), vertebral column fractures (11), and pelvic fractures (4). Thirty
      six patients required inpatient hospitalization; 18 had surgery. The minimum
      healthcare costs associated with these injuries were estimated at $220,000.
      CONCLUSIONS: Major trauma potential is associated with sledding, especially where
      significant winter storms are uncommon. Level I trauma centers should seasonally
      incorporate sledding safety into community-wide injury prevention programs.

PMID- 10071667
TI  - Roles of physicians, attorneys, and illness experience in advance directives.
AB  - BACKGROUND: Age, illness severity, functional status, and education are
      associated with advance directive completion. We examined these patient
      characteristics and discussions with attorneys and physicians in a predictive
      model for advance directive completion. METHODS: We did a cross-sectional survey
      of 255 randomly selected patients in a VA outpatient clinic. RESULTS: Patients
      were predominantly men (95.2%), married (61.9%), with a mean age of 63.2 years;
      17.7% of the patients had an advance directive; 5.0% had only a living will, 6.0%
      had only a durable power of attorney for health care, and 6.7% had both. Age,
      marital status, illness severity, previous serious illness in spouse, and
      physician discussion were all associated with advance directive completion in a
      multiple logistic regression. Eighty-two patients were asked about discussions
      with attorneys--15 had advance directives; of these, 13 had talked to an
      attorney, but only 7 had talked to a physician. CONCLUSIONS: Previous serious
      spousal illness, marital status, age, illness severity, and patient-physician
      discussions all predicted completions of an advance directive. Attorney
      discussions were strongly associated with advance directive completion. Better
      communication between physicians, patients, and attorneys may increase the
      usefulness of advance directives.

PMID- 10071668
TI  - Detection of sentinel lymph nodes with lymphazurin in cervical, uterine, and
      vulvar malignancies.
AB  - BACKGROUND: Identification of sentinel lymph nodes may allow prediction of
      metastatic disease in cancer patients. We did a prospective study to determine
      whether lymphazurin dye could identify sentinel lymph nodes in patients with
      cervical, uterine, and vulvar cancer. METHODS: In 33 patients having surgery for
      either uterine, cervical, or vulvar carcinoma, lymphazurin dye was injected into
      the respective organs before the tumor and node dissection began. Sentinel lymph
      nodes were identified and dissected in situ. RESULTS: The identification rate of
      sentinel lymph nodes was 0/8 (0%) for uterine cancer patients, 2/13 (15.4%) for
      cervical cancer patients, and 9/12 for vulvar cancer patients (75%). CONCLUSIONS:
      In a limited number of patients, lymphazurin day may be useful in identifying or
      assessing the sentinel nodes draining vulvar and cervical cancers. The role of
      this procedure in treatment planning for patients with gynecologic malignancies
      is yet to be determined.

PMID- 10071669
TI  - Usefulness of acute phase reactants in the diagnosis of acute infections in HIV
      infected children.
AB  - BACKGROUND: Children infected with the human immunodeficiency virus (HIV) often
      have hypergammaglobulinemia, causing elevation of the erythrocyte sedimentation
      rate (ESR). This study was done to determine whether C-reactive protein (CRP) is
      a better indicator of acute infection than ESR in HIV-infected children. METHODS:
      Erythrocyte sedimentation rate, CRP, and immunoglobulin G (IgG) levels were
      measured in sick and otherwise healthy HIV-infected children. McNemar's test was
      used to compare ESR and CRP. RESULTS: In 22 of the 26 cases (85%), the IgG level
      was elevated, and in all cases ESR was elevated. In 20 of these 22 (91%), both
      ESR and CRP were elevated. Of the 18 controls, 17 (94%) had elevated IgG, 14 of
      17 (82%) had elevated ESR, and 1 (7%) had elevated CRP. The sensitivity for ESR
      and CRP was 96% and 92%, respectively, and the specificity for ESR and CRP was
      17% and 94%, respectively. CONCLUSIONS: Since CRP is more specific than ESR in
      predicting acute infection in HIV-infected children, it should be used in the
      evaluation of acute infection in this population.

PMID- 10071670
TI  - Comparison of the use and accuracy of methods for determining pleural fluid pH.
AB  - BACKGROUND: The blood gas analyzer (BGA) has been considered the "gold standard"
      for pleural fluid pH determination. METHODS: We report the various methods used
      to measure pleural fluid pH by 277 acute care institutions who responded to a
      mailed questionnaire. The techniques used included the BGA (32%), dip stick or pH
      indicator paper (56%), and a pH meter (12%). We tested 36 consecutive exudative
      pleural fluid samples using each method. RESULTS: The alternative methods were
      incomparable to accurately measuring pleural fluid pH by the BGA, with a mean
      difference of 0.16 pH unit. With a delay in testing, the pH of the pleural fluid
      was more alkalotic and variable, with a mean difference of 0.039 pH unit.
      CONCLUSIONS: Clinicians should be encouraged to test selected samples for pleural
      fluid pH by the BGA when accurate measurements will influence therapy.

PMID- 10071671
TI  - The diagnosis of cor triatriatum sinistrum in children: a continuing dilemma.
AB  - Cor triatriatum (CT) is a rare congenital cardiac anomaly. The salient clinical,
      roentgenographic, electrocardiographic, echocardiographic, and hemodynamic
      findings are presented in two asymptomatic children and one with nonspecific
      dyspnea on exertion. Two male children had a classical form of cor triatriatum
      with normal physical and inconsequential roentgenographic and
      electrocardiographic findings. One of the male patients had surgery for a large
      atrial septal defect ostium secundum (ASD 2 degrees) and pulmonary hypertension
      in infancy. The female patient had CT with a communicating accessory chamber to
      right atrium and a rare patent foramen ovale. Her clinical findings confirmed an
      atrial level shunt. All patients had excision of the fibromuscular membrane from
      the right and left atrial transseptal approach with excellent results and with no
      recurrence during 2 to 4 year follow-up. We report the dilemma encountered in the
      clinical diagnosis of CT in children and the pivotal role played by
      echocardiography in the diagnosis of this anomaly.

PMID- 10071672
TI  - Lead toxicity from gunshot wound.
AB  - Lead toxicity from gunshot wound is a rare complication. It occurs when body
      fluids, especially synovial cavity fluids, dissolve lead from the bullets,
      resulting in absorption and toxicity. Metabolic stress, infection, or alcoholism
      can also enhance absorption. Combination of chelation and surgical removal can
      result in favorable prognosis. Awareness of this condition allows appropriate
      diagnostic and therapeutic interventions to be initiated in a timely manner.

PMID- 10071673
TI  - Flavobacterium meningosepticum sepsis in an infant with a diarrheal prodrome.
AB  - A full term, previously normal 2 1/2-month-old black boy was transferred to our
      hospital from an outlying facility on hospital day 5 for failure to thrive. Three
      weeks before transfer, the infant was hospitalized for a diarrheal illness with
      fever. The baby received 3 days of ceftriaxone empirically and was discharged
      home after the sepsis evaluation was negative. Mild diarrhea and steady weight
      loss continued and the baby was readmitted. Blood culture done on admission grew
      Flavobacterium meningosepticum, an organism previously described as an uncommon
      cause of sepsis in neonates and immunocompromised individuals. As it is water
      borne, it has been associated with infection via contaminated water. This
      organism is usually resistant to antibiotics commonly used for empiric treatment.
      To our knowledge, this is the first reported case of Flavobacterium bacteremia
      associated with a prodromal and concurrent diarrheal illness.

PMID- 10071674
TI  - Acetazolamide relieves concurrent episodic movement disorders encountered in
      Southern states.
AB  - Patients with episodic or paroxysmal movements or postures often are thought to
      have hysteric or psychosomatic illnesses. Kinesigenic (movement-induced)
      posturing similarly is usually misinterpreted. This case is notable because of
      the presence of symptoms of two distinct diseases with similar symptoms and
      changes from one dystonic posture to another during three different durations of
      attack. The condition improved with acetazolamide therapy. The effect of
      acetazolamide on sodium and potassium ionophores is discussed because of new
      genetic information about these illnesses.

PMID- 10071675
TI  - Hantavirus pulmonary syndrome.
AB  - We present the first case of Hantavirus pulmonary syndrome in the Dallas/Fort
      Worth area. The patient was a 50-year-old previously healthy white man, who had
      adult respiratory distress syndrome (ARDS) and hypotensive shock after 1 week of
      nonspecific "viral" symptoms. Despite supportive care, the patient died within
      several hours of presentation. This case illustrates several of the classic
      hallmarks of hantavirus infection such as hemoconcentration, thrombocytopenia,
      ARDS, and shock.

PMID- 10071676
TI  - Striking cholestatic liver disease: a distinct manifestation of advanced primary
      amyloidosis.
AB  - In patients with systemic amyloidosis, amyloid fibrils are typically deposited in
      numerous organs, including the kidneys, heart, and liver. Although amyloid
      deposition in the liver is common in patients with systemic amyloidosis, clinical
      liver disease is relatively rare. The patient described here had cholestatic
      liver disease as the primary manifestation of primary systemic amyloidosis.
      Review of the literature suggests that prominent liver disease with cholestasis
      is unusual but probably underreported in patients with amyloidosis and appears to
      be restricted to patients with the primary form of amyloidosis. Nonetheless,
      cholestatic hepatic amyloidosis is characterized by distinct clinical,
      laboratory, and pathologic features; recognition of this process is critical
      because it identifies patients with widespread organ involvement and portends a
      poor prognosis.

PMID- 10071677
TI  - Treating elder neglect: collaboration between a geriatrics assessment team and
      adult protective services.
AB  - Neglect is the most common type of elder maltreatment in the United States.
      Currently, the only formal intervention available is provided by each state's
      adult protective service agency (APS). Elder neglect involves a complicated
      relationship among an indvidual's medical problems, social situation, and ability
      to function in the environment. Geriatric assessment teams are facile at dealing
      with such complex cases while APS caseworkers are expert in their ability to
      identify and confirm neglect. Forming a geriatric team that includes APS
      caseworkers is a logical and innovative approach to the growing problem of elder
      neglect.

PMID- 10071678
TI  - Pulmonary bone marrow embolism in sickle cell disease.
AB  - We report an unusual lethal complication of sickle cell anemia. The patient was
      admitted with a diagnosis of acute chest syndrome and died shortly after that of
      respiratory failure. Autopsy revealed numerous deposits of bone marrow
      hematopoietic tissue occluding the microvascular circulation of the lung. Many
      causes of acute chest syndrome in sickle cell anemia have been identified,
      including bone marrow infarction leading to embolism of bone marrow fat. However,
      the release of bone marrow hematopoietic tissue leading to pulmonary vascular
      occlusion is not generally recognized premortem by treating physicians.

PMID- 10071679
TI  - Cirrhotic ascites, ovarian carcinoma, and CA-125.
AB  - We describe two postmenopausal women with ascites and elevated CA-125 level, a
      serologic marker used to detect ovarian cancer. Both patients had unrecognized
      liver disease but underwent surgical exploration for suspected ovarian disease,
      which subsequently revealed benign pelvic organs. Elevated serum CA-125 levels
      have been reported in many patients with ascites due to liver disease and
      cirrhosis. Thus, the presence of both ascites and an elevated CA-125 level
      mandates a thorough elevation for liver disease as well as for a possibility of
      ovarian carcinoma. These cases outline the common finding and provide insight
      into the management of patients with ascites and elevated CA-125 values.

PMID- 10071680
TI  - Profound hypothermia and circulatory arrest with skull base approaches for
      treatment of complex posterior circulation aneurysms.
AB  - OBJECTIVE: Cardiopulmonary bypass with profound hypothermia and circulatory
      arrest has seen a resurgence as an adjunct technique in neurological surgery. We
      report our experience with this technique in treating seven complex vertebro
      basilar aneurysms. METHODS: Skull base approaches were used in all cases,
      providing excellent exposure and minimizing brain retraction. There were six
      basilar artery aneurysms and one giant fusiform vertebro-basilar artery aneurysm.
      All aneurysms but one had an apparent neck, which could be clipped. The fusiform
      vertebro-basilar artery aneurysm was trapped, partially resected, and the
      circulation was reestablished with a saphenous vein graft from the cervical
      internal carotid artery to the mid-basilar artery. RESULTS: Five patients had an
      excellent outcome and two had a good outcome at one year or at latest follow up.
      Two of the patients showed improvement of neurological deficits which were
      present before the surgical intervention. CONCLUSION: Applying very strict
      selection criteria in this small series of patients with posterior circulation
      aneurysms, excellent or good results were achieved using the profound hypothermic
      circulatory arrest technique.

PMID- 10071681
TI  - Intra-arterial infusion of fasudil hydrochloride for treating vasospasm following
      subarachnoid haemorrhage.
AB  - In this pilot study we treated cerebral vasospasm in patients with subarachnoid
      haemorrhage to assess intra-arterial fasudil hydrochloride. We analysed effects
      of intra-arterial infusion on angiographically evident cerebral vasospasm in 10
      patients including 3 with symptoms of vasospasm. Over 10 to 30 min 15 to 60 mg
      was administered via the proximal internal carotid artery or vertebral artery
      following standard angiography, without superselective techniques. A total of 24
      arterial territories (21 internal carotid, 3 vertebral) were treated.
      Angiographic improvement of vasospasm was demonstrated in 16 arterial territories
      (local dilation in 2, diffuse dilation in 14) in 9 patients. In 2 symptomatic
      patients, intra-arterial fasudil hydrochloride was associated with resolution of
      symptoms without sequelae. In the third symptomatic patient the benefit of
      fasudil hydrochloride was only temporary, and a large cerebral infarction
      occurred. All asymptomatic patients showed no progression of angiographic to
      symptomatic vasospasm after treatment with intra-arterial fasudil hydrochloride.
      No adverse effect was encountered.

PMID- 10071682
TI  - Long-term results in patients treated with posterior instrumentation and fusion
      for degenerative scoliosis of the lumbar spine.
AB  - The authors report a homogeneously investigated and surgically treated series of
      40 patients with degenerative scoliosis of the lumbar spine. The series included
      22 females and 18 males with a mean age of 62.8 years. The clinical presentation,
      the diagnostic work-up, the indication for surgery, the surgical techniques and
      results are reported. Final evaluation was possible in 30 patients at a mean
      period of observation of 59.5 months. Following a very precise diagnostic and
      therapeutic protocol excellent, good and satisfactory surgical results were
      obtained in 13 (43.3%), 16 (53.3%) and 1 (3.3%) patients, respectively. While
      scoliosis was converted from a mean preoperative Cobb angle of 18.7 degrees to
      7.6 degrees mean pre-operative lumbar lordosis was slightly augmented from 37
      degrees to 41.5 degrees. The results suggest that maintainance or correction of
      lumbar lordosis is more important than the conversion of the scoliotic deformity
      which is probably treated sufficiently by partial correction and stabilization.
      Observation over time indicates that the degenerative cascade evolves despite
      internal fixation and fusion in the majority of the patients until a stable state
      is reached. This stable state is probably rather the result of ankylosis of the
      facet joints than the effect of posterolateral fusion.

PMID- 10071683
TI  - Outcome of traumatic optic neuropathy. Comparison between surgical and
      nonsurgical treatment.
AB  - 34 patients with indirect traumatic optic neuropathy were studied to identify
      factors affecting outcome and surgical indications. 12 cases (13 eyes = group A)
      underwent surgery and 24 patients (24 eyes = group B) were managed without
      surgery. Age, optic canal fracture, visual acuity before treatment (initial
      visual acuity) and days until surgery (only group A) were employed as variables.
      Visual acuity improved significantly more in patients with initial visual acuity,
      hand movement (HM) or better than in those with initial visual acuity for light
      perception (LP) only or worse. When initial visual acuity was HM or better,
      vision improved significantly more in patients with surgery than in those without
      surgery (p = 0.0003 by Mann-Whitney U test). Days until surgery were correlated
      with visual improvement in patients with visual acuity HM or better. Age and
      optic canal fracture did not affect visual improvement or influence the decision
      for or against surgery.

PMID- 10071684
TI  - Monitoring of intracranial compliance: correction for a change in body position.
AB  - The objectives of our study were 1. to investigate whether the intracranial
      compliance changes with body position; 2. to test if the pressure-volume index
      (PVI) calculation is affected by different body positions; 3. to define the
      optimal parameter to correct PVI for changes in body position and 4. to
      investigate the physiological meaning of the constant term (P0) in the model of
      the intracranial volume-pressure relationship. Thirteen patients were included in
      this study. All patients were subjected to 2 to 3 different body positions. In
      each position, either classic bolus injection was performed for measurement of
      intracranial compliance and calculation of PVI or the new Spiegelberg compliance
      monitor was used to calculate PVI continuously. Four different models were used
      for calculating the constant pressure term P0 and the P0 corrected PVI values.
      Pressure volume index not corrected for the constant term P0 significantly
      decreased with elevating the patients head (r = 0.70, p < 0.0001). In contrast,
      volume-pressure response and ICP pulse amplitude did not change with position.
      Using the constant term P0 to correct the PVI we found no changes between the
      different body positions. Our results suggest that during the variation in body
      position there is no change in intracranial compliance but a change in
      hydrostatic offset pressure which causes a shifting of the volume-pressure curve
      along the pressure axis without its shape being affected. PVI measurements should
      either be performed only with the patient in the 0 degree recumbent position or
      that the PVI calculation should be corrected for the hydrostatic difference
      between the level of the ICP transducer and the hydrostatic indifference point of
      the craniospinal system close to the third thoracic vertebra.

PMID- 10071685
TI  - Colloidal blood volume expansion during high intracranial pressure.
AB  - This study tested the hypothesis that colloidal blood volume expansion could
      improve the cerebral circulation during high intracranial pressure. We studied
      cerebrovascular haemodynamic variables during high intracranial pressure with and
      without colloidal blood volume expansion in 12 pigs, whereas five pigs served as
      controls with intracranial pressure increase twice without colloidal blood volume
      expansion. Cerebral blood flow was measured with ultrasonic flowmetry on the
      internal carotid artery, and cerebral microcirculation with laser Doppler
      flowmetry. High intracranial pressure was induced by infusion of artificial
      cerebrospinal fluid into the cisterna magna. Blood volume expansion was obtained
      by infusion of albumin, 1 gram/kg. Albumin infusion caused increases in internal
      carotid artery blood flow (P < 0.05) and cerebral perfusion pressure (P < 0.005),
      while cerebral microcirculation and cerebrovascular resistance was unchanged.
      High intracranial pressure albumin infusion caused internal carotid artery blood
      flow (P < 0.05) and cerebral perfusion pressure (P < 0.001) to increase compared
      to high intracranial pressure without albumin infusion, while cerebrovascular
      resistance was unchanged. Cerebral micro-circulation tended to increase, but this
      was not statistically significant (P = 0.07). Augmentation of the intravascular
      blood volume during high intracranial pressure increased the arterial inflow to
      the brain and possibly the cerebral microcirculation by increasing the cerebral
      perfusion pressure. Our results tend to support that the effect of colloidal
      blood volume expansion is beneficial for the cerebral circulation during high
      intracranial pressure.

PMID- 10071686
TI  - Delayed visual deterioration after surgery for pituitary adenoma.
AB  - Despite its description in the literature there remains uncertainty about the
      incidence, the pathophysiological basis and the best management of a delayed
      visual deterioration in the presence of an empty sella after surgery for
      pituitary adenomas. Out of a series of 501 patients with pituitary adenomas
      operated on at our institution between 1984 and 1996, four patients (0.8%)
      developed a worsening of their visual function 3 to 37 months after surgery in
      the absence of tumour recurrence. None of the patients had received radiotherapy.
      Magnetic resonance imaging (MRI) ruled out compression by tumour and showed
      herniation of suprasellar structures into an empty sella. In three cases re
      operation by a subfrontal approach with freeing of the optic structures from
      tethering scar tissue led to an improvement of visual deficits. In one case a
      spontaneous recovery was initiated by a minor head injury. Although apparently a
      rare event, our cases provide evidence for the occurrence of a potentially
      reversible delayed deterioration of visual function after surgery for pituitary
      adenomas. Based on our operative findings and our outcome we recommend re
      operation by a transcranial approach in patients in whom repeated
      ophthalmological testing does not show spontaneous improvement within a short
      period of time.

PMID- 10071687
TI  - P53 overexpression and proliferative potential in malignant meningiomas.
AB  - Meningiomas are generally benign, but some meningiomas show malignancy with
      invasion and high recurrence rates. We investigated whether alterations in p53
      protein may contribute to malignant progression in meningiomas. Immunostaining
      for p53 protein was performed on paraffin and frozen sections from 61 patients
      with different grades of meningiomas using monoclonal antibodies (mAbs) DO-1 and
      pAb240. Immunoblot analysis was performed to quantitate the amount of p53
      protein. Mutations in p53 genes were assessed by single-strand conformational
      polymorphism (SSCP) analysis. MIB-1 immunostaining was used to detect
      proliferative potentials of meningiomas. We found an overexpression of p53
      protein in all of five cases of anaplastic meningiomas by immunohistochemistry
      using DO-1 mAb. No p53 positive cells were recognized in atypical meningiomas,
      and several cells were weakly stained in only two of 52 benign meningiomas. p53
      staining index and immunoblot analysis indicated increasing amounts of p53
      protein associated with subsequent recurrences of anaplastic meningiomas. The MIB
      1 staining index was positively correlated with tumour grade and p53 protein
      overexpression. Immunostaining of frozen sections using the mutant-specific mAb
      pAb240, as well as mutation gene analysis by SSCP, indicate that the
      overexpressed p53 protein is not a mutant-but wild-type p53 protein. Four
      atypical meningiomas did not recur after surgical removal and radiation, while 4
      anaplastic meningiomas with overexpressed p53 protein recurred repeatedly at
      short intervals even after radiation. Our results suggest that accumulation of
      p53 protein associated with highly proliferative potentials is a common and
      characteristic feature that may indicate malignant biological behaviour in
      meningiomas.

PMID- 10071688
TI  - Prognostic factors in supratentorial ganglioglioma.
AB  - Although gangliogliomas are often associated with long survival, efforts to
      identify specific prognostic factors in these tumors have been largely
      unsuccessful. To identify factors associated with long survival, we
      retrospectively reviewed 42 cases of supratentorial ganglioglioma surgically
      treated at our institution since 1985. Data analysis included Kaplan-Meier
      survival curves and log-rank tests of the effects of individual variables. The
      Cox proportional hazards method was used to fit a model incorporating several
      variables simultaneously. The 42 cases included 21 male and 21 female patients
      with an average age at surgery of 31 years. Length of follow-up averaged 48
      months. Ten patients died an average of 38 months after surgery. Factors found to
      have a significant correlation with mortality were older age at diagnosis (P =
      0.012), male gender (P = 0.034), and malignant glial features (P = 0.020).
      Presenting symptoms, location of tumor, adjuvant radiation therapy, and extent of
      surgical resection were not significantly related to survival. These results are
      the first to demonstrate an association between prognostic factors and outcome in
      patients with supratentorial ganglioglioma.

PMID- 10071689
TI  - Usefulness of motor functional MRI correlated to cortical mapping in Rolandic low
      grade astrocytomas.
AB  - The indications for surgery of slow growing tumours like low grade astrocytomas
      in eloquent areas are difficult. The timing and the benefit/risk ratio of the
      surgery must be evaluated, taking into account the potential post operative
      deficit. The purpose of this study was: a) to validate the data obtained with
      functional MRI (FMRI) by direct cortical stimulation in patients who are
      candidate for surgery; b) to demonstrate the usefulness of FMRI coupled with
      cortical brain mapping and 3D reconstructions of the surfaces of the brain in low
      grade astrocytoma. FMRI of the hand-motor cortex was performed in 8 patients with
      low grade astrocytomas. They subsequently underwent direct cortical mapping to
      correlate the results of FMRI and resective surgery sparing the functional area.
      In the 8 cases, the results of direct cortical mapping in the precentral region
      matched accurately those obtained from FMRI. When surgical resection of low grade
      astrocytoma in the motor areas is considered, FMRI used with intra-operative
      cortical mapping can help the surgeon to spare functional areas during tumour
      removal.

PMID- 10071690
TI  - Paraganglioma of the cauda equina region--report of two cases and review of the
      literature.
AB  - A paraganglioma of cauda equina region is extremely rare and except for secreting
      tumour, the pre-operative diagnosis of paraganglioma is very difficult. Two cases
      of non-functional paragangliomas of the cauda equina region are reported, one was
      attached to the filum terminale and the other to a rootlet looking very much like
      a vascular neurinoma. Both were successfully removed by surgery. An extensive
      review of the literature permits one to find 77 other cases. The clinical,
      radiological, pathological (ultrastructural and immunohistochemical) features and
      surgical findings of all theses cases are discussed. Surgery remains the
      treatment of choice. No effect of radiotherapy on recurrence prevention has ever
      been demonstrated.

PMID- 10071691
TI  - Technical note: a new model for quantitative analysis of brain oedema resolution
      into the ventricles and the subarachnoid space.
AB  - OBJECTIVE: The aim of the current study was to develop an experimental animal
      model for quantitative analysis of oedema resolution via the subarachnoid space
      and the ventricular system using fluorescent oedema markers. METHODS: Artificial
      cerebrospinal fluid (CSF) containing TRITC-albumin (MW 67.000D) and Na(+)
      fluorescein (MW 376D) was continuously infused into the white matter of the left
      frontal lobe of New Zealand white rabbits (n = 6) at a rate of 100 microliters/h
      for 3 hrs. A closed cranial window for superfusion of the brain surface with
      artificial CSF fluid (3 ml/h) was implanted above the left parietal cortex for
      measurement of the fluorescence markers in the subarachnoid space. Uptake of the
      fluorescence indicators into the ventricles was quantified by ventriculo
      cisternal perfusion (3 ml/h). The effluates were collected at 30 min intervals
      for 3 hrs after the start of infusion. Clearance of the oedema fluid into the
      perfusates was measured by fluorescence spectrophotometry. RESULTS: At an
      intracranial pressure of 15.0 +/- 1.7 mm Hg (mean +/- SEM) both indicators
      started to accumulate in the subarachnoid and ventricular perfusates at 90 min
      following onset of oedema fluid infusion. The concentrations of the indicators in
      the ventricular system increased to 7.7 +/- 5.1% of Na(+)-fluorescein and 16.1 +/
      13.0% of TRITC-albumin of the total amount infused were recovered in the
      ventricular system at 3 hours after start of the oedema infusion, while 3.4 +/-
      3.2% of Na(+)-fluorescein and 3.7% +/- 3.2 of TRITC-albumin, respectively, were
      found in the effluates of the subarachnoid space. CONCLUSION: The present study
      demonstrates that resolution of vasogenic brain oedema into the cerebral
      ventricular system and the subarachnoid space following its entry into cerebral
      white matter can be quantitatively analysed using fluorescence markers, which
      serve as oedema fluid indicators. The results indicate that the oedema fluid is
      cleared not only into the ventricular system but also via the subarachnoid space.

PMID- 10071692
TI  - Protective effect of the N-methyl-D-aspartate receptor antagonists, MK-801 and
      CPP on cold-induced brain oedema.
AB  - Cold injury model in rat was used to determine the effect of treatment with the
      competitive NMDA antagonists CPP and the non-competitive NMDA antagonist MK-801
      in cerebral oedema. MK-801 was applied in doses of 1 mg/kg and CPP of 10 mg/kg,
      15 min. after injury. Control animals received 1 ml saline at the same time
      interval after injury. Tissue samples from the core and periphery of the lesion
      of the injured hemisphere and from the symmetrical location of the undamaged
      contralateral hemisphere were removed 24 hours after injury. Blood brain barrier
      permeability, brain water content and tissue specific gravity values were
      determined. MK-801 was found beneficial for reducing the oedema and restore the
      blood brain barrier permeability at the penumbral zone of the lesion, whereas
      both MK-801 and CPP were found ineffective for prevention of oedema accumulation
      at the core of the lesion.

PMID- 10071693
TI  - Basilar artery occlusion due to spontaneous basilar artery dissection in a child.
AB  - Basilar artery occlusion (BAO) causing brainstem infarction occurred in a 7-year
      old boy without any basic disorders. A diagnosis of BAO due to basilar artery
      dissection (BAD) was suspected at angiography, and this was confirmed by
      gadolinium-enhanced magnetic resonance imaging (MRI). These investigations
      clearly showed all the typical diagnostic signs such as a pseudolumen, double
      lumen and intimal flap, and a pseudolumen in resolution. The spontaneous healing
      of the dissection was clearly demonstrated during 10 months of follow-up. We
      stress that BAD can occur in young children and that combined diagnosis with
      gadolinium-enhanced MRI and angiography is conclusive for diagnosis of dissecting
      aneurysms. Wider use of these combined diagnostic methods will allow the
      detection of less severe basilar artery dissection, thus extending the spectrum
      of presentation and prognosis.

PMID- 10071694
TI  - An unusual cause of spinal paraplegia intramedullary schistosomiasis.

PMID- 10071695
TI  - Intensive care units: achieving utopia.

PMID- 10071696
TI  - What would Vesalius think?

PMID- 10071697
TI  - Point-of-care laboratory testing in critical care.
AB  - BACKGROUND: Critical care practitioners are searching for ways to improve the
      quality and outcomes of care while decreasing cost and length of stay. One
      technological advance that may facilitate meeting these objectives is bedside or
      point-of-care laboratory equipment. Evaluation of point-of-care testing for
      application in each institution requires information about the devices available;
      knowledge of the advantages and disadvantages of the technologies, the clinical
      impact, and cost of the process change; and strategies for successful
      implementation. OBJECTIVES: To review the literature on point-of-care testing and
      the experience of healthcare professionals who have already successfully
      implemented this type of testing. METHODS: A total of 81 relevant published
      articles were reviewed, and 21 critical care units in 8 facilities that use point
      of-care testing were visited. Open-ended interviews were conducted with 83
      subjects: 56 nurses, 14 laboratory personnel, 9 respiratory therapists, and 4
      others. CONCLUSIONS: Point-of-care testing is a technological innovation with the
      potential for improving patients' care without increasing costs. It most likely
      will soon become part of the standard of care.

PMID- 10071698
TI  - Effects of injectate volume on thermodilution measurements of cardiac output in
      patients with low ventricular ejection fraction.
AB  - OBJECTIVE: To determine the effect of 5-mL injectate on cardiac output
      measurements in critically ill patients with low ventricular ejection fraction (<
      35%). METHODS: Thermodilution cardiac output measurements obtained with three 5
      mL and three 10-mL (randomly ordered) iced injectates in 50 patients with low
      ejection fraction were averaged if the measurements were within 10% of the
      median. If the 3 measurements were not within those limits, additional
      measurements were obtained. RESULTS: Cardiac output measured with the 5-mL
      injectate (mean, 4.63 L/min) and cardiac output measured with the 10-mL injectate
      (mean, 4.52 L/min) were not significantly different (P = .64). Lower and upper
      limits of agreement were -1.7 L/min to +1.6 L/min. The bias (mean difference
      between 10- and 5-mL measurements) of all measurements was -0.09, and the
      precision was 1.43 L/min, with a 95% confidence limit (mean difference +/- 2 SD)
      of -1.7 to +1.6 L/min. An additional measurement was necessary in 77% of patients
      in the 5-mL group but in only 48% of the 10-mL group (P = .006). CONCLUSIONS:
      Cardiac outputs measured with 5- and 10-mL injectates do not differ
      significantly. The greater variability of measurements obtained with a 5-mL
      injectate suggests that more measurements, and thus more time, are needed to
      measure cardiac output accurately. Clinicians must weigh the benefit of
      minimizing fluid volume used against the potential decreased reliability of
      cardiac output measurements.

PMID- 10071699
TI  - Endotracheal tube narrowing after closed-system suctioning: prevalence and risk
      factors.
AB  - BACKGROUND: Few data exist about buildup of secretions within endotracheal tubes
      of patients treated with closed-system suctioning in the intensive care unit.
      OBJECTIVES: To describe the extent, prevalence, and distribution of narrowing of
      endotracheal tubes related to buildup of secretions and to determine contributing
      factors. METHODS: Forty endotracheal tubes were examined within 4 hours of
      extubation, after at least 72 hours of use. Data on patients' daily weight and
      fluid balance, ventilator humidification temperatures, and nurses' descriptions
      of secretions during the 3 days preceding extubation were recorded. Any secretion
      debris in the endotracheal tubes was weighed. At 1-cm intervals along the tube,
      the debris was described and the depth of the debris was measured to the nearest
      0.5 mm. RESULTS: Mean duration of intubation was 6.6 days. Two tubes had no
      debris. Mean overall depth of debris was 0.64 mm, mean greatest depth was 2.0 mm
      (range, 0-5 mm), and mean weight was 1.16 g. The entire tube was affected, with
      the greatest depth of debris at the 6- to 9-cm and 13- to 14-cm markings.
      Duration of intubation correlated with mean greatest depth of debris (r = 0.37, P
      = .02), mean overall depth of debris (r = 0.48, P = .002), and mean weight of
      debris (r = 0.38, P = .02). CONCLUSIONS: Endotracheal tubes are markedly narrowed
      by the buildup of secretions after closed-system suctioning. Duration of
      intubation, but not endotracheal tube size or amount of secretions, was
      associated with the degree of narrowing.

PMID- 10071700
TI  - Differences in African American and white women with myocardial infarction:
      history, presentation, diagnostic methods, and infarction type.
AB  - BACKGROUND: Despite overall declining death rates from cardiovascular disease,
      the number of women dying of cardiovascular disease increases each year, with
      substantially higher rates in African American women than in white women.
      OBJECTIVE: To investigate differences in presentation, diagnostic method, and
      type of infarction between African American and white women with myocardial
      infarction. METHODS: Chart review of all women with discharge diagnosis of
      myocardial infarction. RESULTS: No significant differences were found between
      African American and white women in admitting diagnosis, diagnostic methods, or
      type of infarction. At the time of admission, 2 medical history variables, stroke
      and hypertension, differed significantly between African American and white women
      (P = .027 and P = .002, respectively). CONCLUSIONS: Healthcare professionals must
      be aware of possible racial differences in medical history, signs and symptoms,
      and prognosis when assessing patients and planning interventions. Studies with
      larger samples are needed to confirm these findings on African American and white
      women with myocardial infarction.

PMID- 10071701
TI  - Pain assessment and management in critically ill postoperative and trauma
      patients: a multisite study.
AB  - BACKGROUND: Pain in critically ill patients is undertreated. OBJECTIVES: To
      examine patients' perceptions of pain and acute pain management practices in a
      large metropolitan area to provide direction for improvements in pain relief.
      METHODS: In a descriptive, correlational study, data were collected from 213
      patients in 13 hospitals. Interviews with patients, chart reviews, and interviews
      with nurse leaders were used to examine institutional and individual approaches
      to pain management. RESULTS: Twenty-eight percent of patients did not recall an
      explanation of a pain management plan, and 64% were often in moderate to severe
      pain while in the intensive care unit. High pain intensity correlated with wait
      for an analgesic (P < .001), expectations of less pain (P < .001), and longer
      stay in the intensive care unit (P < .001). Low satisfaction correlated with
      expectations of less pain (P < .001), often being in moderate to severe pain (P <
      .001), and long wait for an analgesic (P < .001). In the first 24 hours
      postoperatively, only 54% of patients had a numerical pain rating documented; 91%
      had a pain description. The amount of opioid given on postoperative day 1 was
      influenced by pain intensity (P < .001), the patient's age (P = .03), type of
      surgery (P = .002), and route of analgesic (P < .001). Only 33% of patients had
      nonpharmacological pain interventions documented. CONCLUSIONS: Despite moderate
      to severe pain, patients are generally satisfied with their pain relief.
      Measuring patients' satisfaction alone is not a reliable outcome for determining
      the effectiveness of pain management. Realistic expectations of patients about
      their pain may enhance coping, increase satisfaction, and decrease pain intensity
      after surgery.

PMID- 10071702
TI  - Stress during mechanical ventilation: benefit of having concrete objective
      information before cardiac surgery.
AB  - BACKGROUND: Negative emotional reactions and difficulty in communicating are
      common in patients receiving mechanical ventilation and may adversely affect
      recovery from cardiac surgery. OBJECTIVE: To determine the effect of providing
      concrete objective information about emotional stress and difficulty in
      communicating related to mechanical ventilation to Korean cardiac surgery
      patients. METHODS: A quasi-experimental 2-group design was used. The 22 subjects
      in the control group received the usual information; the 21 in the experimental
      group received concrete objective information in addition to the usual
      information. State anxiety, negative affect, use of sedative and analgesic
      medications, and difficulty communicating were compared between the 2 groups
      after surgery. RESULTS: Patients who received concrete objective information
      experienced less anxiety and negative mood during mechanical ventilation, less
      difficulty in communicating, and a shorter intubation time than did patients in
      the control group. The 2 groups did not differ in the amount of sedative or
      analgesic medication used per hour during mechanical ventilation. CONCLUSIONS:
      Nursing interventions that include concrete objective information help cardiac
      patients cope with the stresses associated with surgery and mechanical
      ventilation.

PMID- 10071703
TI  - Inherited thrombophilic syndromes and the use of ventricular assist devices.

PMID- 10071704
TI  - The use of antioxidants in retarding atherosclerosis: fact or fiction?
AB  - The proposal that antioxidants may retard the progression of atherosclerosis is
      not new. Published studies examining the effect of antioxidants on experimental
      antioxidants extend back to 1940. The results have all been inconsistent.
      However, the data regarding the beneficial effects of retarding atherosclerotic
      progression are strong enough to warrant continued research on the lipoprotein
      oxidation theory or atherosclerosis. However, caution is needed to avoid
      embracing a concept without proof. It should be noted that the National
      Cholesterol Education Program does not recommend the use of antioxidant vitamin
      supplements to reduce CAD. Atherogenesis is produced by multiple factors. To
      believe that all such factors are mediated by uncontrolled oxidative events is,
      to say the least, naive. Finally, should antioxidants prove to be effective in
      retarding coronary atherosclerosis, their place on the therapeutic ladder of CAD
      prevention would be low. The overwhelmingly proven evidence favors the following
      factors that have been proven to lower morbidity and mortality due to
      atherosclerosis: (a) treatment of hypertension, (b) cessation of tobacco use, (c)
      treatment of dyslipidemia, (d) achieving a normal weight, (e) regular exercise,
      (f) treatment of homocystinuria, especially in cases with renal disease, and (g)
      antioxidants.

PMID- 10071705
TI  - Newer antipsychotics in treatment-resistant schizophrenia.

PMID- 10071706
TI  - A combined TMS/fMRI study of intensity-dependent TMS over motor cortex.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) allows noninvasive
      stimulation of neurons using time-varying magnetic fields. Researchers have begun
      combining TMS with functional imaging to simultaneously stimulate and image brain
      activity. Recently, the feasibility of interleaving TMS with functional magnetic
      resonance imaging (fMRI) was demonstrated. This study tests this new method to
      determine if TMS at different intensities shows different local and remote
      activation. METHODS: Within a 1.5 Tesla (T) MRI scanner, seven adults were
      stimulated with a figure-eight TMS coil over the left motor cortex for thumb,
      while continuously acquiring blood oxygen level dependent (BOLD) echoplanar
      images. TMS was applied at 1 Hz in 18-second long trains delivered alternately at
      110% and 80% of motor threshold separated by rest periods. RESULTS: Though the
      TMS coil caused some artifacts and reduced the signal to noise ratio (SNR),
      higher intensity TMS caused greater activation than lower, both locally and
      remotely. The magnitude (approximately 3% increase) and temporal onset (2 to 5
      sec) of TMS induced blood flow changes appear similar to those induced using
      other motor and cognitive tasks. CONCLUSIONS: Though work remains in refining
      this potentially powerful method, combined TMS/fMRI is both technically feasible
      and produces measurable dose-dependent changes in brain activity.

PMID- 10071707
TI  - Cell biology of the hippocampal formation in schizophrenia.
AB  - The hippocampal formation (HF) has been a centerpiece of neuropathologic
      investigations of schizophrenia. Numerous MRI studies have demonstrated a slight
      bilateral reduction in HF volume. Reports of reduced N-acetyl aspartate measured
      with in vivo proton spectroscopy suggest that neuronal pathology exists. However,
      morphometric data from postmortem studies have not revealed a clear change in HF
      size, and recent studies of neuronal number and of cytoarchitecture have been
      largely negative. Evidence of glial proliferation is consistently absent. The
      most reproducible positive anatomic finding in postmortem HF has been reduced
      size of neuronal cell bodies. Studies of gene transcription have provided
      replicable evidence of decreased expression of mRNAs for synaptophysin, GAP-43,
      cholecystokinin, and non-NMDA glutamate receptor subunits (GLU R 1 and 2),
      particularly in CA 3-4. These data about the cellular and molecular biology of
      the HF in schizophrenia are different from that found in a number of conditions
      associated with hippocampal damage, including excitotoxicity, epilepsy,
      alcoholism, Alzheimer's disease, steroid neurotoxicity, and normal aging.
      Notwithstanding the real possibility that the data are epiphenomena of chronic
      illness, the findings may implicate a unique cellular defect in schizophrenia--a
      genetic variation affecting the plasticity of HF circuitry and connectivity.
      Directions for further research are proposed.

PMID- 10071708
TI  - Comparative efficacy of olanzapine and haloperidol for patients with treatment
      resistant schizophrenia.
AB  - BACKGROUND: There is relatively little information regarding the efficacy of
      newer atypical antipsychotic drugs for patients with schizophrenia who are
      treatment-resistant to neuroleptic agents. Several lines of evidence suggest that
      a clinical trial of olanzapine in this population is warranted. METHODS: A
      subpopulation of patients (n = 526) meeting treatment-resistant criteria selected
      from a large, prospective, double-blind, 6-week study assessing the efficacy and
      safety of olanzapine and haloperidol were examined. Both last-observation-carried
      forward (LOCF) and completers (observed cases) analyses were conducted. RESULTS:
      Olanzapine demonstrated significantly greater mean improvement from baseline in
      Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid
      depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale,
      akathisia as measured by Barnes Akathisia Scale, and extrapyramidal symptoms as
      measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and
      completers analyses. In addition, olanzapine was significantly superior to
      haloperidol for Brief Psychiatric Rating Scale total (p = .006), PANSS total (p =
      .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study.
      Significantly greater response rates were observed in olanzapine-treated (47%)
      than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but
      significance was not reached in the completers analysis (p = .093). Mean doses
      (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6
      mg/day, respectively. CONCLUSIONS: Olanzapine was superior to haloperidol for key
      symptom domains and parkinsonian side effects. Implications of these data for the
      therapeutics of this severely ill subgroup are discussed.

PMID- 10071709
TI  - A study of motor dysfunction associated with schizophrenia based on analyses of
      movement-related cerebral potentials and motor conduction time.
AB  - BACKGROUND: Several reports have shown that schizophrenics have motor
      dysfunction. The aim of this study was to identify the site of the nerve damage
      responsible for the motor dysfunction in schizophrenics by measuring both
      movement-related cerebral potentials (MRCPs) and motor conduction times. METHODS:
      The subjects were 27 patients and 31 controls. There was no significant
      difference in age, nor in the length of the subjects' arms between the two
      groups. MRCPs were recorded during voluntary self-paced index movements of the
      thumb. The motor nerve conduction time was determined by magnetically stimulating
      the motor cortex and the spinal root. RESULTS: Six of 27 schizophrenics had
      normal MRCPs, but the remaining 21 showed abnormal MRCPs. Of the 31 controls, 27
      were normal, whereas 4 showed abnormal MRCPs. The difference between the two
      groups was significant; however, no significant differences were found in the
      motor conduction times, the motor root conduction times, or the central motor
      conduction times between the two groups. CONCLUSIONS: Our results suggest that
      the responsible focus of motor nerve disorder in schizophrenia lies in the motor
      integrating system in frontal lobe, and not in the nervous conduction system from
      the brain to the muscles.

PMID- 10071710
TI  - Melatonin secretion rhythm disorders in patients with senile dementia of
      Alzheimer's type with disturbed sleep-waking.
AB  - BACKGROUND: There is growing evidence that the dysregulation of circadian rhythms
      may play an important role in irregular sleep-waking in demented elderly. In this
      study, we investigated daily variation of the pineal hormone melatonin, which has
      been reported to possess hypnogenic and synchronizing effects, in patients with
      senile dementia of Alzheimer's type. METHODS: Serum melatonin secretion rhythms
      in inpatients with senile dementia of Alzheimer's type (SDAT group, n = 10,
      average age = 75.7 years) with disturbed sleep-waking and nondemented elderly (ND
      group, n = 10, age = 78.3 years) without clinical sleep disorders in the same
      facility were monitored under a dim light condition without excessive physical
      exercise. RESULTS: The SDAT group showed a significantly higher degree of
      irregularities in actigraphically recorded rest-activity (R-A) rhythm during the
      7-day baseline period compared with the ND group. The SDAT group simultaneously
      showed significantly reduced amplitude, larger variation of peak times, and
      diminished amount of total secretion in the melatonin secretion rhythm compared
      with the ND group. There were significantly positive correlations between the
      severity of R-A rhythm disorder and the reduced amplitude as well as diminished
      amount of total melatonin secretion. CONCLUSIONS: The SDAT patients with
      disturbed sleep-waking possessed melatonin secretion rhythm disorders that may
      play an important role in irregular sleep-waking in demented elderly.

PMID- 10071711
TI  - Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease.
AB  - BACKGROUND: The apolipoprotein E (ApoE) epsilon 4 allele confers significant risk
      for Alzheimer's disease and is associated with a greater amyloid burden in the
      brain. Future treatments may target molecular mechanisms associated with this
      allele, and it is important to define any phenotypic characteristics that
      correspond to this genotype. We sought to clarify the relationship between ApoE
      status and noncognitive symptoms in Alzheimer's disease patients. METHODS:
      Possible and probable Alzheimer's disease patients from a clinical trial (n =
      605) were assessed with the 10-item Neuropsychiatric Inventory cross-sectionally
      prior to treatment, and their ApoE genotype was determined. Among the population
      studied, the following numbers with specific genotypes were studied: 23-2/3, 17
      2/4, 209-3/3, 288-3/4, 68-4/4. RESULTS: When correlations were controlled for the
      patient's level of cognitive impairment, there was no relationship between
      epsilon 4 dose and any of the 10 noncognitive symptoms assessed, including
      psychosis, mood changes, and personality alterations. CONCLUSIONS: Among patients
      with comparable disease severity, the epsilon 4 allele does not confer additional
      psychiatric morbidity.

PMID- 10071712
TI  - CYP2D6 polymorphisms in Alzheimer's disease, with and without extrapyramidal
      signs, showing no apolipoprotein E epsilon 4 effect modification.
AB  - BACKGROUND: Allelic variation at the CYP2D6 gene has been reported to be
      associated with Parkinsons' disease (PD) and Lewy body dementia (LBD), but not
      with Alzheimer's disease (AD). AD has been associated with apolipoprotein E
      (apoE) epsilon 4 allele loading. METHODS: We examined CYP2D6 and apoE
      polimorphisms in a sample of 259 patients with dementia, 210 of whom had a
      diagnosis of AD, and 107 healthy controls. RESULTS: We found that the allelic
      frequency in our AD sample did not vary from that in the controls. The
      debrisoquine hydroxylase poor metabolize phenotype was not more prevalent among
      AD cases than among controls in contrast to that reported for PD and LBD. We also
      found that CYP2D6 status does not modify the risk effect for AD conferred by apoE
      epsilon 4 alleles. CONCLUSIONS: These findings provide some support to the notion
      that, at a genetic level, at least at this locus, AD could be distinct from PD
      and LBD.

PMID- 10071713
TI  - Apolipoprotein E-epsilon 4 frequency in affective disorder.
AB  - BACKGROUND: The epsilon 4 allele of apolipoprotein E (APOE) as well as affective
      disorder have been found to be associated with Alzheimer's disease, but it is
      unclear whether cognitive impairment in affective disorder or subtypes of
      affective disorder is mediated by the epsilon 4 allele of APOE. METHODS: The
      genotype of APOE was analyzed in 106 unipolar patients, 21 bipolar patients, and
      46 controls and correlated with cognitive function in the euthymic phase as
      measured by the Mini-Mental State Examination, the Cambridge Cognitive
      Examination, the Mattis Dementia Rating Scale, the Gottfries-Brane-Steen Dementia
      Rating Scale, and the Global Deterioration Scale. RESULTS: The frequency of APOE
      epsilon 4 allele was approximately the same in unipolar patients (.189) and in
      bipolar patients (.167). Although patients showed more cognitive impairment than
      controls, no significant overall difference was found between the frequency of
      APOE-epsilon 4 allele in patients (.185) and controls (.131). In fact, the
      frequency of APOE-epsilon 4 allele did not correlate with cognitive impairment.
      It was not possible to identify subgroups of patients with an increased frequency
      of APOE-epsilon 4 allele, as no association was found with gender, age at onset,
      the number of affective episodes, the presence of psychotic features, or the
      prevalence of familial affective disorder. CONCLUSIONS: It seems that cognitive
      impairment in affective disorder can be attributed to pathways other than the
      APOE genotype.

PMID- 10071714
TI  - Polygraphic sleep criteria as predictors of successful aging: an exploratory
      longitudinal study.
AB  - BACKGROUND: A cohort of 57 elderly healthy volunteers (34 male, 23 female) was
      studied in a sleep laboratory on four consecutive nights when their average age
      was 63.5 +/- 3.7 years. Thirty subjects (20 male, 10 female) were assessed 14
      years later; 21 had either died in the meantime or were very ill, and 6 did not
      participate for other reasons. METHODS: Two operationalizations of successful
      aging were applied: survival in relatively good health (30 survivors vs. 21
      nonsurvivors), and cognitive competence as assessed in the survivors by means of
      tests of cognitive function. RESULTS: Whereas none of the sleep characteristics
      determined at baseline distinguished the survivors from the nonsurvivors, several
      parameters [REM (rapid eye movement) sleep latency, REM density, and NREM (non
      REM) shifts] were significantly correlated with one or more measures of cognitive
      functioning at follow-up. These polygraphic sleep parameters also distinguished a
      subgroup of cognitively fully competent subjects from those who, according to
      their performance in tests of cognitive function, could be considered as mildly
      demented. CONCLUSIONS: While the REM latency and density findings support the
      theory of a functional link between brain cholinergic activity, timing, and
      density of REM sleep and cognitive functioning, the positive association between
      the number of NREM shifts at baseline and cognitive performance 14 years later is
      difficult to explain. It is suggested that the findings of the present study, in
      particular the potential predictive value of REM latency and REM density for
      cognitive functioning in the old, need replication in other subject samples
      followed for similar time periods.

PMID- 10071715
TI  - Regulation of the platelet serotonin transporter by protein kinase C in the young
      and elderly.
AB  - BACKGROUND: Some data show that different factors may influence the serotonin (5
      HT) uptake rate. Our study aimed at evaluating the possible role of a protein
      kinase C (PKC) activator, i.e., 4-beta-12-tetradecanoylphorbol-13-acetate (beta
      TPA) on the platelet 5-HT uptake of young and elderly subjects, through the
      measurement of the 5-HT uptake itself and 3H-paroxetine ([3H]PAR) binding sites,
      which correspond to the transporter protein. METHODS: Human platelets and 5-HT
      uptake were evaluated according to the method of Arora and Meltzer, while [3H]PAR
      binding was performed following the Marazziti et al method. RESULTS: The results
      showed that beta-TPA reduced significantly the maximal velocity (Vmax) of 5-HT
      uptake, with no change in the Michaelis constant or in [3H]PAR binding
      parameters, in platelets of both young and elderly subjects. Although this last
      group of subjects had a significantly lower Vmax than the other, the degree of
      inhibition was almost the same (75%) in both. CONCLUSIONS: These findings
      indicate that PKC decreases the 5-HT uptake rate by modifying the phosphorylation
      state of the transporter and with no change in the number of [3H]PAR binding
      sites. The responsiveness of this pathway is identical in both young and elderly
      subjects.

PMID- 10071716
TI  - Decreased dopamine beta-hydroxylase activity in unipolar geriatric delusional
      depression.
AB  - BACKGROUND: Decreased dopamine beta-hydroxylase (DBH) activity has been reported
      in unipolar psychotic depression. DBH comparisons between elderly delusional and
      nondelusional depressives and controls and determination of whether pretreatment
      group differences persist have not been reported. Our objective was to compare
      DBH activity in elderly delusional major depressives with that of nondelusional
      depressives and normal control subjects before and after hospital treatment.
      METHODS: Enzyme activity was assessed after hospital admission. A subsample had
      predischarge assessments. Treatment was not controlled but accounted for in
      analyses. Electroconvulsive therapy subjects were medication-free for
      posttreatment assays. RESULTS: Baseline and predischarge DBH assays were lower in
      subjects with delusional depression than in either comparison group. Despite high
      intraindividual correlation, treatment was associated with significant increases
      in activity in the clinical groups. CONCLUSIONS: Patients with late-life
      delusional depression have lower DBH activity before and after hospital treatment
      than age-matched nondelusional patients or normal controls.

PMID- 10071717
TI  - Platelet membrane phospholipids in euthymic bipolar disorder patients: are they
      affected by lithium treatment?
AB  - BACKGROUND: Abnormalities in cell membrane processes and intracellular signal
      transduction pathways may be implicated in the pathophysiology of bipolar
      disorder. In this study, we attempted to investigate, in euthymic bipolar
      patients: 1) in vivo signal transduction abnormalities of the
      phosphatidylinositol pathway in platelets; and 2) possible in vivo effects of
      lithium treatment on platelet membrane phospholipids. METHODS: We determined the
      relative absorbances of eight individual classes of platelet membrane
      phospholipids, using two-dimensional thin-layer chromatography in high
      performance plates, followed by scanning laser densitometry, in a group of 10
      lithium-treated euthymic bipolar patients and 11 normal controls. RESULTS: The
      mean relative absorbance of phosphatidyl-inositol-4,5-bisphosphate (PIP2) was
      lower in the patient group (0.29 +/- 0.08% vs. 0.39 +/- 0.12%; t = 2.35, df = 19,
      p = .03); no significant differences between patients and controls were found for
      the other phospholipids. CONCLUSIONS: This study provides in vivo evidence that
      bipolar patients on lithium treatment exhibit a decreased relative amount of PIP2
      in the platelet cell membranes compared to normal controls.

PMID- 10071718
TI  - Major depression, heart rate, and plasma norepinephrine in patients with coronary
      heart disease.
AB  - BACKGROUND: Although it is now well established that psychiatric depression is
      associated with adverse outcomes in patients with coronary heart disease (CHD),
      the mechanism underlying this association is unclear. Elevated heart rate (HR)
      and plasma norepinephrine (NE), possibly reflecting altered autonomic nervous
      system activity, have been documented in medically well depressed psychiatric
      patients, and this pattern is associated with increased risk for cardiac events
      in patients with CHD. The purpose of this study was to determine whether
      autonomic nervous system activity is altered in depressed CHD patients. METHODS:
      HR, plasma NE, and blood pressure (BP) were measured in 50 depressed and 39
      medically comparable nondepressed CHD patients at rest and during orthostatic
      challenge. RESULTS: Resting HR (p = .005), and the change from resting HR at 2,
      5, and 10 min after standing (p = .02, .004, and .02, respectively), were
      significantly higher in the depressed than in the nondepressed patients. There
      were no differences between the groups in NE or in BP at rest, or in standing
      minus resting change scores at any time during orthostatic challenge (p < .05).
      CONCLUSIONS: Depression is associated with altered autonomic activity in patients
      with CHD, as reflected by elevated resting HR and an exaggerated HR response to
      orthostatic challenge. Previously reported differences in NE levels between
      depressed and nondepressed patients were not replicated.

PMID- 10071719
TI  - Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal
      affective disorder and the effect of bright light therapy.
AB  - BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin
      disorder, but the pathophysiological mechanisms of SAD are to a large extent
      unclarified. Serotonergic mechanisms have also been studied, but they have shown
      inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic
      acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23
      controls. Then SAD patients had 4 weeks of light therapy. On the last treatment
      day new blood samples were drawn. Symptoms before and after light treatment were
      measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment
      was higher in SAD patients compared to controls and also higher in responders
      than in nonresponders. Bmax decreased significantly during light treatment. We
      also found a negative correlation between the two Bmax values before but not
      after light treatment. There was a negative correlation between Bmax for
      paroxetine binding before treatment and clinical status after treatment. Patients
      with reduced Bmax for LSD binding after treatment had a better clinical treatment
      response. CONCLUSIONS: The present study indicates that serotonin receptor
      parameters might be suitable in the prediction of clinical response to light
      treatment.

PMID- 10071720
TI  - Lymphocyte subset, lymphocyte proliferative response, and soluble interleukin-2
      receptor in anorexic patients.
AB  - BACKGROUND: Despite a prominent malnourished state, anorexics are unexpectedly
      free from infection. Several studies have shown that the cell-mediated immunity
      of anorexics might be well preserved, but results are conflicting. METHODS:
      Lymphocyte subsets, lymphoproliferative response to phytohemagglutinin, and
      soluble interleukin-2 receptor (sIL-2R) were measured in 7 patients with anorexia
      nervosa restricting type (RAN), 6 with anorexia nervosa binge-eating/purging type
      (ANBP), and 8 controls (C). RESULTS: Compared with controls, significantly
      elevated percentage of CD4 and CD4/CD8 ratio in ANBP was found. Although there
      was no significant difference in lymphoproliferative response among the three
      groups, sIL-2R in RAN was significantly lower than that in the C group, but not
      in ANBP. CONCLUSIONS: Although detail mechanism still remains to be unknown, some
      kinds of compensatory mechanism for cell-mediated immunity is working, especially
      in chronic underweight anorexic patients.

PMID- 10071721
TI  - Thioperamide, a histamine H3 receptor antagonist, powerfully suppresses peptide
      YY-induced food intake in rats.
AB  - BACKGROUND: Whether or not peptide YY (PYY)-induced hyperphagia is modified by
      the histaminergic system in the brain is not yet known. METHODS: We investigated
      the effect on feeding of intracerebroventricular (ICV) administration of a
      specific histamine H3 receptor antagonist prior to ICV administration of PYY in
      rats. RESULTS: PYY (1, 3, and 10 micrograms/10 microL) strongly induced feeding
      behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced
      by 3 micrograms/10 microL of PYY was equal to that induced by a 16-hour fast. The
      ICV administration of thioperamide (40.8, 122.4, and 408.5 micrograms/10 microL)
      did not suppress the 4-hour food intake induced by 16-hour fasting; however,
      thioperamide produced dose-dependent and strong inhibition of hyperphagia induced
      by a 3-microgram dose of PYY. CONCLUSIONS: These results suggest that the effect
      of PYY on appetite is different than that induced by fasting and may involve a
      histaminergic mechanism.

PMID- 10071722
TI  - Enhanced visual latent inhibition in obsessive-compulsive disorder.
AB  - BACKGROUND: Latent inhibition (LI) is the slowed acquisition of a learned
      response to a conditioned stimulus (CS), that occurs if that CS has previously
      been experienced in a noncontingent setting. This retarded acquisition is thought
      to occur because, due to the previous noncontingent experience, an individual
      must "unlearn the irrelevance" of the CS, before learning its new association to
      the unconditioned stimulus. A previous report using an auditory paradigm did not
      detect abnormal LI in obsessive-compulsive disorder (OCD) subjects; this auditory
      LI task included a difficult acquisition phase, which made it relatively
      insensitive to detecting abnormally elevated LI (i.e., slowed "unlearning").
      METHODS: We assessed LI using a highly sensitive computerized visual LI paradigm
      in 63 carefully screened control subjects and in 48 patients with OCD. RESULTS:
      Compared to controls, OCD subjects exhibited significantly more LI; if
      "preexposed" to a to-be-CS, OCD subjects required significantly more trials to
      learn a new association to that CS, compared to control subjects. This pattern
      was particularly evident in unmedicated OCD subjects. CONCLUSIONS: The inflated
      impact of preexposure on LI response acquisition in OCD subjects may be a
      quantitative measure of their tendency to remain "stuck in set" in this cognitive
      task.

PMID- 10071724
TI  - Event-related potential index of semantic mnemonic dysfunction in abstinent
      alcoholics.
AB  - BACKGROUND: The objective of the study was to expand the investigation of the
      match/mismatch mnemonic impairment in the semantic domain in sober alcoholics.
      METHODS: Event-related potentials (ERPs) were recorded from 28 healthy adults and
      36 sober alcoholics in a category (either animals or fruits/vegetables)
      match/nonmatch S1-S2 paradigm. RESULTS: There was a significant interaction of
      ERP amplitude (c3) between groups (controls vs. alcoholics) and stimulus
      conditions (category match vs. nonmatch) at the posterior brain regions; the c3
      component was smaller for the category match than for nonmatch trials in
      controls, with the absence of such c3 differences in alcoholics. There were no
      significant ERP differences between the two groups in processing the sample
      stimuli. The ERPs c2) elicited by the animal category were larger than those for
      the vegetable category in both groups. The alcoholics showed prominent suppressed
      activation of left temporooccipital brain regions under both matching and
      nonmatching conditions, as demonstrated by the current source density maps. The
      alcoholics were also slower and less accurate than the controls in judging both
      category matching and nonmatching stimuli, while neither of the two groups
      demonstrated shorter response times to the matching stimuli. CONCLUSIONS: These
      data suggest that alcoholics are less efficient in the semantic mnemonic
      match/nonmatch process, and are less likely to be deteriorated in the stage of
      forming the template for such match/nonmatch comparisons.

PMID- 10071723
TI  - Blood ethanol levels and adenylyl cyclase activity in lymphocytes of alcoholic
      patients.
AB  - BACKGROUND: The adenylyl cyclase (AC) signal transduction pathway is a target of
      acute and chronic ethanol actions. This study examined whether AC activity in
      lymphocyte membranes of male alcoholic patients correlated with blood
      concentrations of ethanol. METHODS: Patients (n = 13; mean age: 40 +/- 8 years)
      were studied on the day of admission (day 0) and 2 days later under
      detoxification. Moreover, 13 age-matched male healthy controls (mean age 40 +/- 9
      years) were included. Lymphocyte membranes were prepared by differential
      centrifugation whereby blood ethanol was washed out. As a measure of AC activity
      the formation of cyclic adenosine monophosphate (cAMP) from adenosine
      triphosphate was determined without (basal activity) and with stimulation of the
      second messenger system by the guanosine triphosphate (GTP) analogue GTP gamma S
      (20 mumol/L) via the G-protein or by forskolin (100 mumol/L) acting directly on
      the AC enzyme. RESULTS: On day 0, when ethanol blood concentrations were 38-100
      mmol/L, we found a significant negative correlation between ethanol blood levels
      and stimulated AC activities. On day 2, the negative correlation with blood
      ethanol levels of day 0 had disappeared. CONCLUSIONS: The consumption of ethanol
      affects the AC system in lymphocytes of alcohol-dependent patients by a
      persistent effect on the cAMP forming enzyme.

PMID- 10071725
TI  - Antimicroglia antibodies in sera of Alzheimer's disease patients.
AB  - BACKGROUND: Immune mechanisms seem to contribute to the degenerative process in
      Alzheimer's disease. Antibodies directed against animal brain tissue were found
      in sera of Alzheimer's patients. METHODS: Antibodies were measured in sera of 25
      Alzheimer's patients and a comparison group of 25 age- and sex-matched controls.
      Sera were tested for their immunological response to various brain structures of
      postmortem human brain tissue. RESULTS: In 8 patients with Alzheimer's disease
      perinuclear antibodies directed against microglia were found in amygdala and
      frontal cortex. In the control group 1 subject showed antibody binding to
      microglia. CONCLUSIONS: Perinuclear antibodies to microglia may play a role in
      tissue destruction of Alzheimer's disease. These data add to the evidence that
      immune mechanisms play a role in the pathophysiology of Alzheimer's disease.

PMID- 10071726
TI  - A placebo-controlled crossover trial of D-cycloserine added to clozapine in
      patients with schizophrenia.
AB  - BACKGROUND: D-Cycloserine, a partial agonist at the glycine recognition site of
      the NMDA receptor, has previously been shown to improve negative symptoms when
      added to conventional antipsychotics and, in one preliminary dose-finding study,
      worsened negative symptoms when added to clozapine. METHODS: Seventeen
      schizophrenia outpatients treated with clozapine were assigned in random order to
      6-week trials of D-cycloserine 50 mg/day and placebo in a crossover design
      separated by a 1 week placebo washout. RESULTS: Eleven patients competed the 13
      week study. D-Cycloserine significantly worsened ratings of negative symptoms
      compared to placebo but did not significantly affect ratings of psychotic
      symptoms. CONCLUSIONS: The differing effects of D-cycloserine on negative
      symptoms when added to clozapine compared to conventional antipsychotics suggests
      that activation of the glycine recognition site may play a role in clozapine's
      efficacy for negative symptoms.

PMID- 10071727
TI  - Syndrome of inappropriate antidiuretic hormone.

PMID- 10071728
TI  - Wrinkles.

PMID- 10071729
TI  - Dermatitis in actors, dancers, singers, and circus performers.

PMID- 10071730
TI  - What's eating you? Triatome reduviids.

PMID- 10071731
TI  - Hereditary palmoplantar keratoderma with nail changes and periodontosis in a
      father and son.

PMID- 10071732
TI  - Botfly infestation (myiasis) masquerading as furunculosis.
AB  - With air travel so prevalent, diseases endemic to certain regions may appear
      anywhere. The botfly (Dermatobia hominis) is not native to North America. We
      describe a case of a young boy and his father who presented with furunculosis
      secondary to infestation with the botfly. The infected patients live in South
      Florida and had been vacationing in Central America. Standard surgical treatment
      as well as multiple native remedies are described.

PMID- 10071733
TI  - Amyopathic dermatomyositis associated with transitional cell carcinoma of the
      bladder.
AB  - Transitional cell carcinoma of the bladder is the most common tumor of the
      urinary tract. However, it has only been reported twice in the literature to be
      associated with the paraneoplastic syndrome dermatomyositis. We report a case of
      amyopathic dermatomyositis in a patient whose painless gross hematuria was due to
      transitional cell carcinoma of the bladder as well as review this association.

PMID- 10071734
TI  - Multiple cutaneous granular cell tumors of the scrotum.
AB  - A 55-year-old black man with two firm intradermal nodules of the scrotum is
      presented. On histopathologic examination, the nodules were determined to be
      cutaneous granular cell tumors. This was confirmed by strong immunohistochemical
      reactivity to S-100 protein. There are no previous reports of multiple granular
      cell tumors of the male genitalia. Only one report of a solitary granular cell
      tumor of the scrotum appears in the literature.

PMID- 10071735
TI  - A potpourri of parasitic infestations.
AB  - Ectoparasitic infestations are common cutaneous problems. The vast majority of
      these are attributable to scabies and pediculosis. While these are usually
      readily recognizable, infestations caused by other ectoparasites, such as
      nonscabetic mites, may pose difficulty in diagnosis. In this article, we present
      a variety of ectoparasitic infestations that initially eluded diagnosis and
      review the gamut of ectoparasites that can cause eruptions in the skin.

PMID- 10071736
TI  - Leukocytoclastic vasculitis, hepatitis B, and the risk of endoscopy.
AB  - Leukocytoclastic vasculitis, presenting with palpable purpura, is a relatively
      common problem encountered by both primary care practitioners and dermatologists.
      A variety of potential etiologies exists and includes autoimmune, neoplastic, and
      infectious causes. We report a case of leukocytoclastic vasculitis that led to
      the diagnosis of acute hepatitis B, perhaps acquired through colonoscopy.

PMID- 10071737
TI  - Prominent hyperkeratotic plantar and palmar warts.
AB  - We report the case of a 28-year-old man who had prominent hyperkeratotic plantar
      and palmar warts, and flat warts on his face and chest. By DNA hybridization,
      human papillomavirus 1 and/or 2, and 3 DNA were detected from the tissues of
      these skin lesions. Results of laboratory investigations revealed leukopenia,
      eosinophilia, anti-HBs antigen and anti-hepatitis C virus antibody, and decrease
      in the OKT4/OKT8 ratio. He had no abnormality in cellular immunity. He was
      treated with multiple modalities, but was successfully treated with
      electrocautery to the plantar and palmar warts, and cryotherapy with liquid
      nitrogen to the flat warts. Nine years after the initial treatment, almost no
      recurrence was recognized.

PMID- 10071738
TI  - Dermatofibrosarcoma protuberans in an infant with a history of choroid plexus
      papilloma.
AB  - We describe an infant with a dermatofibrosarcoma protuberans (DFSP) who also had
      a choroid plexus papilloma. This report underscores the occurrence of DFSP in
      this age group and may support a neural pathogenesis of this tumor.

PMID- 10071740
TI  - Comments on managed care as they relate to the November 1998 editorial, "Last
      call for freedom (yours)".

PMID- 10071739
TI  - Prurigo pigmentosa: a misdiagnosed dermatitis in Sicily.
AB  - Prurigo pigmentosa is a papular pruriginous eruption that leaves a marble-like
      pigmentation. The majority of cases have been found in Japan. Three new female.
      Sicilian patients with prurigo pigmentosa were studied. All of them had
      previously been diagnosed as having different types of dermatitis. The
      administration of minocycline, at a dosage of 100 mg/day for 1 month, induced the
      disappearance of the papular eruption and pruritus in two patients, with an
      improvement of the gross reticular pigmentation. The third showed no
      modifications of the clinical picture after 2 months of minocycline treatment,
      but her condition significantly improved after 1 month of treatment with
      diaminodiphenylsulfone, 100 mg/day. These observations allow us to suggest that
      prurigo pigmentosa might be relatively frequent but misdiagnosed in the Sicilian
      population.

PMID- 10071741
TI  - Comments on managed care as they relate to the November 1998 editorial, "Last
      call for freedom (yours)".

PMID- 10071742
TI  - Management of onychomycosis.

PMID- 10071743
TI  - Dye rashes.
AB  - Physicians may administer intravenous dyes to patients, most commonly to
      delineate vascular or urinary anatomy, without an appreciation of the potential
      hazards associated with these compounds. We report two cases in which skin
      eruptions followed the intravenous administration of the dyes fluorescein and
      methylene blue; these eruptions were the same colors as the dyes. In our first
      patient, urticaria, which was yellowish in color and fluorescent under a Wood's
      lamp, occurred after the administration of fluorescein. In the second patient,
      painful blue macules appeared randomly on the forearm within 15 seconds after
      methylene blue was injected into a free-flowing intravenous cannula on the dorsal
      aspect of the hand.

PMID- 10071744
TI  - Body odor in dermatologic diagnosis.
AB  - Patients with an unpleasant body odor often consult dermatologists. A
      dermatologist needs to become familiar with the occurrence and significance of
      medically related odors. Although body odor may be essentially physiological, and
      problems with body mal-odor are paid little attention, they can cause many
      personal troubles and may induce a variety of psychosocial disturbances. Body
      odor in general is an indicator of individual care and hygiene, or results from
      eating garlic, onion, spicy foods, curry, or drinking alcohol; however, in some
      instances it can be pathologic. It is a well-known clinical fact that many
      diseases (both of internal and cutaneous origin), several syndromes, and some
      intoxications cause characteristic, peculiar, and identifiable odors. Their
      identification can provide diagnostic clues, guide the laboratory evaluation, and
      help in the choice of immediate and appropriate therapy. Thus, olfactory
      evaluation can be an important part of clinical examination and olfactory
      diagnosis is still valid in recognizing certain diseases. This report reviews the
      physiological and pathologic body odors and the importance of olfactory diagnosis
      in dermatology.

PMID- 10071745
TI  - Pigmented purpuric dermatosis in a young male.
AB  - The pigmented purpuric dermatoses (PPD) are a group of disorders that most often
      occur on the lower extremities of middle-aged adults as asymptomatic, yellow
      orange patches with petechiae. The PPD represent a benign, often chronic,
      capillaritis of unknown cause. We present a case of PPD on the abdomen of a young
      male and emphasize careful observation in such a patient to reveal possible
      progression to purpuric mycosis fungoides.

PMID- 10071746
TI  - Receptor research prize 1998. Sponsored by NEN Life Science Products. Dr. Werner
      Schlegel.

PMID- 10071747
TI  - Methodology of receptor research--a philosophical perspective.
AB  - Two examples taken from the philosophy of physics (measurement and experiment)
      show the dependence of quantitative data and of causal judgements on technical
      aims that are invested into both laboratory research and the concept formation of
      a successful science. Accordingly, methodology is defined as the theory of
      methods, i.e. of the rules governing actions constitutive of research and the
      phrasing of its results. Judgement on methods is a matter of means-and-ends
      rationality. The objects and relations under consideration are not natural but
      technical ones. With respect to analytical chemistry, a problem concerning the
      application of mathematics to quantitative data is described in order to argue
      for the irreducibility of measurement of macroscopic quantities (like volume) to
      the counting of numbers of micro-objects (like molecules): the basic concepts of
      microbiology, analytic chemistry and toxicology remain related to certain
      theoretical (and corresponding experimental) contexts. Starting from the
      perspective that receptor research is dealing with the effects of chemical
      substances on organisms, a few constraints on receptor research are
      characterised. The idealisation of causes and effects by describing them in terms
      of chemistry (on a molecular level) hinges on a problematic presupposition. It is
      objected that there is neither a way down from levels more complex to simpler
      ones nor a way up from simple to complex levels in so far as the criteria for
      medical diagnoses are not causally linked with chemical descriptions. As a
      result, the significance of the traditional connection between the medical
      treatment of persons and the manageableness of health effects by pharmaceutical
      means is stressed. Whether molecular models, theories and explanations are
      helpful for a phenomenological description has to be tested accordingly but
      cannot generally be presupposed.

PMID- 10071748
TI  - Chance favors the prepared mind--from serendipity to rational drug design.
AB  - Accidental discoveries always played an important role in science, especially in
      the search for new drugs. Several examples of serendipitous findings, leading to
      therapeutically useful drugs, are presented and discussed. Captopril, an
      antihypertensive Angiotensin-converting enzyme inhibitor, was the first drug that
      could be derived from a structural model of a protein. Dorzolamide, a
      Carboanhydrase inhibitor for the treatment of glaucoma, and the HIV protease
      inhibitors Saquinavir, Indinavir, Ritonavir, and Nelfinavir are further examples
      of therapeutically used drugs from structure-based design. More enzyme
      inhibitors, e.g. the anti-influenza drugs Zanamivir and GS 4104, are in clinical
      development. In the absence of a protein 3D structure, the 3D structures of
      certain ligands may be used for rational design. This approach is exemplified by
      the design of specifically acting integrin receptor antagonists. In the last
      years, combinatorial and computational approaches became important methods for
      rational drug design. SAR by NMR searches for low-affinity ligands that bind to
      proximal subsites of an enzyme; linkage with an appropriate tether produces
      nanomolar inhibitors. The de novo design program LUDI and the docking program
      FlexX are tools for the computer-aided design of protein ligands. Work is in
      progress to combine such approaches to strategies for combinatorial drug design.

PMID- 10071749
TI  - Receptors and signalling components of plant hormones.
AB  - Recent advances in understanding plant hormonal signalling has resulted in the
      identification of a variety of signalling components including receptor kinases
      with homology to the bacterial two component system as well as serine/threonine
      kinases and protein phosphatases. In addition, the existence of MAP kinase
      pathways in plants indicates a similar role of these signalling cascades in the
      relay of exogenous signals into the nucleus as has been disclosed in animal
      cells. The emerging signalling pathways of the plant hormone abscisic acid and
      ethylene are presented.

PMID- 10071750
TI  - Extracts and constituents of Hypericum perforatum inhibit the binding of various
      ligands to recombinant receptors expressed with the Semliki Forest virus system.
AB  - Extracts, fractions and constituents of Hypericum perforatum were studied for in
      vitro receptor binding with various ligands to recombinant CNS receptors
      expressed with the Semliki Forest virus expression system. For this purpose we
      have prepared membranes of CHO cells with high density of several opioid,
      serotonin, estrogen, histamine, GABAA, neurokinin and metabotropic glutamate
      receptors, respectively. A lipophilic Hypericum fraction revealed relatively
      potent inhibition to the binding of the mu-, delta- and kappa-opioid and the 5
      HT6 and 5-HT7 receptors. Moreover, Hypericum constituents such as the
      naphthodianthrones, hypericin and pseudohypericin, and the phloroglucinole
      hyperforin inhibited both binding to the opioid and serotonin receptors in the
      lower micromolar range. Estrogen binding was 50% inhibited by the biflavonoid
      I3,II8-biapigenin at micromolar concentration. The lipophilic Hypericum fraction
      provided a less potent inhibition of the neurokinin-1 receptor binding compared
      to the opioid and serotonin receptors. A total ethanolic Hypericum extract
      potently inhibited GABAA binding at approximately 3 micrograms/ml. This
      inhibition is however not specific to Hypericum, since extracts of plants like
      Valeriana officinalis and Passiflora incarnata showed similar inhibitions.
      Binding to neither histamine nor metabotropic glutamate receptors was affected by
      Hypericum extracts. These results support the hypothesis that several active
      constituents of Hypericum might in a synergistic way contribute to its
      antidepressant effect in the central nervous system.

PMID- 10071751
TI  - The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus.
AB  - The Jak-STAT pathway was originally discovered through the study of interferon
      induced intracellular signal transduction. Meanwhile, a large number of
      cytokines, hormones and growth factors have been found to activate Jaks and
      STATs. Jaks (Janus Kinases) are a unique class of tyrosine kinases that associate
      with cytokine receptors. Upon ligand binding, they activate members of the Signal
      Transducers and Activators of Transcription (STAT) family through phosphorylation
      on a single tyrosine. Activated STATs form dimers, translocate to the nucleus,
      bind to specific response elements in promotors of target genes, and
      transcriptionally activate these genes. Both positive and negative regulations of
      the Jak-STAT pathway have been identified. In a positive feedback loop,
      interferons transcriptionally activate the genes for components of the interferon
      stimulated gene factor 3 (ISGF3). A number of cytokines that activate the Jak
      STAT pathway, e.g. IL-6, IL-4, LIF, G-CSF, have been shown to upregulate the
      expression of SOCS-JABs-SSIs, a recently discovered class of STAT inhibitors.
      Targeted disruption of genes for a number of Jaks and STATs in mice have revealed
      specific biological functions for many of them. Although most of the STATs are
      activated in cell culture by many different ligands, STAT knockout mice mostly
      show defects in a single or a few cytokine dependent processes. STAT1 knockout
      mice have an impaired interferon signalling, STAT4 knockouts impaired IL-12
      signalling, STAT5a knockouts impaired prolactin signalling, STAT5b knockouts
      impaired growth hormone signalling, and STAT6 knockout impaired IL-4 and IL-13
      signalling. Defects in the Jak-STAT pathway have already been identified in a
      number of human diseases. Prominent amongst them are leukaemias, lymphomas and
      inherited immunodeficiency syndromes. It can be expected that additional Jak-STAT
      related diseases will be identified over the next years. To date, specific STAT
      inhibitory drugs are not known, but a number of specific protein-protein
      interactions in the Jak-STAT pathway are potential targets for pharmaceutical
      interventions.

PMID- 10071752
TI  - Regulation of protein kinase B.
AB  - Protein kinase B (PKB) is a member of the second-messenger regulated subfamily of
      protein kinases implicated in signalling downstream of growth factor and insulin
      receptor tyrosine kinases and phosphatidylinositol 3-kinase (PI 3-kinase). PKB is
      activated by phosphorylation in response to mitogens and survival factors.
      Membrane recruitment driven by lipid second-messengers derived from PI 3-kinase
      leads to PKB phosphorylation and activation by upstream kinases (PDK1 and an as
      yet identified protein kinase). Prolonged stimulation with growth factors results
      in nuclear translocation, providing evidence that PKB activation at the plasma
      membrane precedes its nuclear translocation and supporting a role for PKB in
      signalling from receptor tyrosine kinases to the nucleus.

PMID- 10071753
TI  - Fluorine-18 radiolabelling, biodistribution studies and preliminary PET
      evaluation of a new memantine derivative for imaging the NMDA receptor.
AB  - A synthetic method has been established for preparing [18F]1-amino-3-fluoromethyl
      5-methyl-adamantane ([18F]AFA). Biodistribution of the radiotracer in mice showed
      high brain uptake. The peak uptake (3.7% I.D/g organ) for the brain occurred at
      30 min after injection. Accumulation of radioactivity in mouse brain was
      consistent with the known distribution of the NMDA receptors. The binding of
      [18F]AFA to the phencyclidine (PCP) binding sites of the NMDA receptor complex
      and the sigma recognition sites in a Rhesus monkey was also examined using
      positron emission tomography (PET). The regional brain distribution of [18F]AFA
      was changed by memantine and by (+)-MK-801, indicating competition for the same
      binding sites. Treatment with haloperidol caused a marked reduction of
      radioactivity uptake in all the brain regions examined. (-)-Butaclamol, which has
      pharmacological specificity for sigma sites, did not have any significant
      effects.

PMID- 10071754
TI  - Analysis of the endocytic pathway upon intracellular transport of IgG molecules
      through Fc receptors.
AB  - The uniformly distributed Fc receptors (FcRs) on the surface of many cell types
      are involved in a variety of immune reactions by non-specifically facilitating
      the entry of antigen-specific IgG molecules to the cell. Such reactions may be
      beneficial to the organism when foreign antigens are involved, or harmful in
      cases of self antigens and viruses. In order to avoid the IgG-mediated self
      antigen presentation or viral infection in autoimmunity and viral attack
      respectively, we attempt in this study to inhibit the intracellular transport of
      antibodies. This blockage, however, implies: efficacy of inhibition, inability of
      de novo exocytosis of the internalised antibody and finally maintenance of normal
      cell growth and morphology. We thus concentrate our interest on the endocytic
      pathway followed by a neutralising antibody in murine trophoblast cells where we
      try to inhibit antibody intracellular transport by various agents according to
      the criteria set above. In our model-system, IFN-gamma, upon induction of FcRs,
      facilitates endocytosis of the anti-p21ras antibody which blocks in turn the IFN
      gamma-induced surface class II major histocompatibility complex (MHC) expression.
      Using various intracellular transport inhibitors, we study the required
      conditions by which these compounds cancel the inhibitory action of anti-p21ras
      and allow induction of class II MHC molecules by IFN-gamma. The effectiveness of
      the inhibitors in a ranking order is shown as following: monodansyl cadaverine >
      didansyl cadaverine > pepstatin A > leupeptin > NH4Cl > brefeldin A > ZPCK >
      TPCK. From these inhibitors, only brefeldin A, leupeptin, pepstatin and ZPCK do
      not allow exocytosis of the antibody in the culture medium and only didansyl
      cadaverine, pepstatin and leupeptin maintain cell viability and morphology.
      However, by sequential elimination based on this study's established criteria,
      only pepstatin A and leupeptin are shown to be effective inhibitors to specific
      antibody intracellular transport, protecting also the cell's viability and
      physiology.

PMID- 10071755
TI  - TP5 triggers signal transduction involving mitogen activated protein kinases in
      monocytes.
AB  - The pentapetide thymopentin (TP5) corresponding to the aminoacids RKDVY
      represents the residues 32-36 of thymopoietin (TP), which was originally isolated
      from bovine thymus. Both were observed to induce T-cell differentiation and
      maturation. Recently however it was shown, that TP represents the N-terminal 49
      aa of the human thymopoietin (TMPO) isoforms TMPO alpha, beta and gamma, which
      are localized in the nucleus. TP5 was investigated in a variety of diseases and
      showed efficacy by improving the immune balance, whereby different cells
      increased in cell number or activity. Findings which support the assumption of
      multifunctional efficacy and a description of TP and TP5 modulating T cells lack
      any interpretation on molecular level. In the present study we investigated the
      binding of TP5 on white blood cells. We identified monocytes and neutrophils as
      TP5-binding cells by displacing fluorescein-labelled TP5 with an excess of
      unlabelled TP5 in competition assays. Binding of TP5 on cell surface proteins
      resulted in cellular signalling and we report here that TP5 triggers signal
      transduction involving mitogen activated protein kinases p42/p44 (MAPKs) in
      monocytes.

PMID- 10071756
TI  - A microplate binding assay for the somatostatin type-2 receptor (SSTR2).
AB  - The clinical importance of somatostatin type-2 receptors (SSTR2) and the study of
      novel analogues of somatostatin such as OctreoScan or [Tyr3]-octreotide
      containing DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as
      metal chelator led us to develop a methodology to monitor the expression of SSTR2
      on tumours of pancreatic origin (e.g. rat AR4-2J cancer cells). Usual binding
      assay protocols using the commercial [125I][Tyr1]-somatostatin radioligand
      failed, even in the presence of a cocktail of protease inhibitors with a broad
      spectrum of activity, possibly due to the high susceptibility of this tracer to
      proteases expressed in pancreatic cells. We prepared our own radioligand
      [125I][Tyr2]-octreotide which was shown to be much more resistant to degradation
      after incubation with AR4-2J plasma membranes. As expected, the increased
      stability of [125I][Tyr3]-octreotide was associated with good binding to SSTR2.
      Addition of appropriate protease inhibitors further increased the specific
      binding of [125I][Tyr3]-octreotide to AR4-2J plasma membranes without affecting
      the stability of the tracer, suggesting that the protease inhibitors also protect
      the integrity of SSTR2. Optimal conditions (time, temperature, medium) were
      developed for a binding assay in 96-well plates using AR4-2J plasma membranes in
      order to make the assay suitable for high-throughput analysis. This protocol was
      the basis for studying the in vivo regulation of SSTR2 expression in AR4-2J cells
      implanted into scid mice after exposure to different compounds.

PMID- 10071757
TI  - Binding of interleukin-13 and interleukin-4 to the interleukin (IL)-4/IL-13
      receptor of human synovial fibroblasts.
AB  - Synovial fibroblasts expressed transcripts for IL-4R alpha, and IL-13R alpha 1
      and IL-13R alpha 2. Using weighted nonlinear computer modeling of the data from
      equilibrium binding studies, a 2 bindings sites model fitted the data best. After
      occupation of the shared high affinity receptors by the non-signaling, double
      mutant IL-4(121)R-->D, 124Y-->D (RY-IL-4) the high affinity binding of IL-13
      could be abolished. A 2 binding site model still could be fitted, however the
      improvement in fit over a onesite model was not statistically significant. Using
      affinity spectra, at least 2 binding sites are apparent. After treatment with RY
      IL-4, some of the high affinity binding was abolished, however not completely. A
      correlation between the number of binding sites and the affinity is apparent,
      which seriously casts doubt on the classical evaluation of binding isotherms,
      where the parameters are assumed to be independent. In a previous study we
      suggested that the large number of IL-13R alpha 2 monomers are silent receptors,
      likely representing a decoy target for IL-13. The high affinity binding therefore
      most likely represents the binding to the heterodimer consisting of IL-4R alpha
      and IL-13R alpha 1 or IL-13R alpha 2. The low affinity binding may represent the
      IL-13R alpha 2.

PMID- 10071759
TI  - Melanocortin and leptin signaling systems: central regulation of catabolic energy
      balance.
AB  - The recent cloning of the ob gene (leptin) has revolutionized our understanding
      of obesity and the underlying factors that govern weight homeostasis. There is
      growing evidence that long term food intake regulation is controlled by the
      central nervous system by a number of peptide hormones in response to changes in
      leptin levels. Studies of these hormones, using both genetic and pharmacological
      approaches, have provided a foundation for decoding the molecular logic of the
      neuronal circuits which regulate food intake control and energy balance. A review
      of the current progress in the melanocortin-4 receptor pathway, with particular
      emphasis on its relation to leptin, neuropeptide Y and other obesity hormones
      known to modulate weight homeostasis, is presented.

PMID- 10071758
TI  - Participation of beta-adrenergic receptors on macrophages in modulation of LPS
      induced cytokine release.
AB  - For several years it is known that beta-adrenergic receptor agonists have anti
      inflammatory effects. However, little is known about the role of beta-adrenergic
      receptors on macrophages in the modulation of cytokine production by beta
      agonists during inflammation. In this study, the presence of beta-receptors on
      PMA-differentiated U937 human macrophages, and the participation of these
      receptors in the modulation of LPS-mediated cytokine production by beta-agonists
      was investigated. Total beta-receptor expression on undifferentiated (monocyte)
      and PMA-differentiated U937 cells was established using receptor binding studies
      on membrane fractions with a radio ligand. The expression of beta-receptors
      proved to be significantly lower on monocytes than on macrophages, additionally a
      predominant expression of beta 2-receptors was found. Production of the cytokines
      TNF-alpha, IL-6, and IL-10 by LPS-stimulated differentiated U937 cells was
      measured in time. Peak concentrations for TNF-alpha, IL-6 and IL-10 occurred at
      3, 12 and 9 hrs, respectively. When differentiated U937 cells were incubated with
      both LPS and the beta-agonist clenbuterol the production of TNF-alpha and IL-6
      was significantly reduced. However the production of IL-10 was increased. To
      study the mechanism of modulation of cytokine production in more detail, U937
      macrophages were incubated with LPS/clenbuterol in combination with selective
      beta 1- and beta 2-antagonists. These results indicated that the beta 2- and not
      the beta 1-receptor is involved in the anti-inflammatory activity of clenbuterol.

PMID- 10071760
TI  - From insulin receptor signalling to Glut 4 translocation abnormalities in obesity
      and insulin resistance.
AB  - Insulin resistance is commonly associated with obesity in rodents. Using mice
      made obese with goldthioglucose (GTG-obese mice), we have shown that insulin
      resistance results from defects at the level of the receptor and from
      intracellular alterations in insulin signalling pathway, without major alteration
      in the number of the Glut 4 glucose transporter. Activation of
      phosphatidylinositol 3-kinase (PI 3-kinase) was found to be profoundly affected
      in response to insulin. This defect appears very early in the development of
      obesity, together with a marked decrease in IRS 1 tyrosine phosphorylation. In
      order to better understand the abnormalities in glucose transport in insulin
      resistance, we have studied the pathway leading from the insulin receptor kinase
      stimulation to the translocation of the Glut 4 containing vesicles. This
      stimulation involves the activation of PI 3-kinase, which in turns activates
      protein kinase B. We have then focussed at the mechanism of vesicle exocytosis,
      and more specifically at the role of the small GTPase Rab4 in this process. We
      have shown that Rab4 participates, first in the intracellular retention of the
      Glut 4 containing vesicles, second in the insulin signalling pathway leading to
      glucose transporter translocation.

PMID- 10071761
TI  - Genomic organization and mutational analysis of the human UCP2 gene, a prime
      candidate gene for human obesity.
AB  - Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are
      involved in dissipating the proton electrochemical gradient thereby releasing
      stored energy as heat. This implies a major role of UCPs in energy metabolism and
      thermogenesis which when deregulated are key risk factors for the development of
      obesity and other eating disorders. Recent studies have shown that the
      sympathetic nervous system, via norepinephrine (beta-adrenoceptors) and cAMP, as
      well as thyroid hormones and PPAR gamma ligands seem to be major regulators of
      UCP expression. From the three different UCPs identified so far by gene cloning
      UCP1 is expressed exclusively in brown adipocytes while UCP2 is widely expressed.
      The third analogue, UCP3, is expressed predominantly in human skeletal muscle and
      was found to exist in a long and a short form. At the amino acid level UCP2 has
      about 59% homology to UCP1 while UCP3 is 73% identical to UCP2. Both UCP2 and
      UCP3 were mapped in close proximity (75-150 kb) to regions of human chromosome 11
      (11q13) that have been linked to obesity and hyper-insulinaemia. Furthermore,
      there is strong evidence that UCP2, by virtue of its ubiquitous expression, may
      be important for determining basal metabolic rate. Based on the published full
      length cDNA sequence we have deduced the genomic structure of the human UCP2
      (hUCP2) gene by PCR and direct sequence analysis. The hUCP2 gene spans over 8.4
      kb distributed on 8 exons. The localization of the exon/intron boundaries within
      the coding region matches precisely the one found in the human UCP1 gene and is
      almost conserved in the recently discovered UCP3 gene as well. However, the size
      of each of the introns in the hUCP2 gene differs from its UCP1 and UCP3
      counterparts. It varies from 81 bp (intron 5) to about 3 kb (intron 2). The high
      degree of homology at the nucleotide level and the conservation of the
      exon/intron boundaries among the three UCP genes suggests that they may have
      evolved from a common ancestor or are the result from gene duplication events.
      Mutational analysis of the hUCP2 gene in a cohort of 25 children of caucasian
      origin (aged 7-13) characterized by low BMR values revealed a point mutation in
      exon 4 (C to T transition at position 164 of the corresponding cDNA resulting in
      the substitution of an alanine residue by a valine at codon 55) and an insertion
      polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat
      located 150 bp downstream of the stop codon in the 3'-UTR. The allele frequencies
      were 0.61 and 0.39 for the alanine and valine encoded alleles, respectively, and
      0.71 versus 0.29 for the insertion polymorphism. Expression studies of the
      wildtype and mutant forms of UCP2 should clarify the functional consequences
      these mutations may have on energy metabolism and body weight regulation. In
      addition, mapping of the promoter region and the identification of putative
      promoter regulatory sequences should give insight into the transcriptional
      regulation of UCP2 expression--in particular by anyone of the above mentioned
      factors--in vitro and in vivo.

PMID- 10071762
TI  - Splice variants of the OB receptor gene are differentially expressed in brain and
      peripheral tissues of mice.
AB  - A high affinity receptor for OB protein was recently cloned from the choroid
      plexus of mice. At least six alternatively spliced forms of the OB receptor (OB
      R) gene have been described, all of which encode proteins containing the OB-R
      extracellular domain. One splice variant encodes a receptor with a long
      intracellular domain, OB-RL, that has been implicated in OB-R signaling. Here, we
      have used in situ hybridization to examine the localization of OB-R splice
      variants in brain and peripheral tissues of adult and newborn mice. Using a probe
      hybridizing with all known splice variants, we confirmed that OB-R mRNA was
      widely distributed in the adult tissues. In the CNS, choroid plexus was the major
      site of expression. We now demonstrate that OB-R mRNA is expressed in peripheral
      tissues; primarily associated with connective tissues. In addition, OB-R mRNA was
      detected at higher levels in peripheral tissues of newborn mice than in adult
      mice. With a probe specific for OB-RL, we confirmed that high mRNA expression was
      detected in hypothalamic nuclei, while low levels were observed in choroid
      plexus. We now report that in peripheral tissues of adult mice, OB-RL mRNA
      expression was either very low or undetectable. In newborn mice, the pattern of
      OB-RL message expression in the CNS was similar to that of adult mice, while bone
      was the site of highest OB-RL message expression in the peripheral tissue. These
      data suggest different biological roles for OB-R splice variants encoding the
      short and long forms of OB-R. The localization of OB-RL to hypothalamic nuclei
      supports the idea that OB-RL is the brain receptor that mediates OB protein
      signaling and actions. In addition, the expression of OB-R message in newborn
      mice also suggests a biological role of OB-R during development in mice.

PMID- 10071763
TI  - Binding of long-term glycated low density lipoprotein and AGE-albumin by
      peripheral monocytes and endothelial cells.
AB  - Modification of low density lipoprotein (LDL) and plasma or tissue proteins by
      non-enzymatic glycation culminating in the formation of advanced glycation
      endproducts (AGEs) is one of the essential pathomechanisms leading to diabetes
      associated long-term complications. We compared binding of glycated, glycoxidated
      and oxidated LDL by peripheral monocytes in activated and quiescent form.
      Interaction via specific receptors was different for glycated as compared to
      (glyc)oxidated LDL-modifications. In addition, binding of glycated LDL to
      quiescent and activated human umbilical vein endothelial cells was studied. In
      patients with insulin-dependent diabetes mellitus (IDDM), AGE-binding was
      significantly increased as compared to healthy individuals. Specific and non
      specific monocyte binding mechanisms were detected, and both were significantly
      increased in IDDM patients. Specific and non-specific binding strategies possibly
      act in concert to eliminate circulating AGEs, which are instrumental in the
      development and progress of microangiopathic and macroangiopathic complications
      of diabetes mellitus.

PMID- 10071764
TI  - Effect of isoflavone genistein on insulin receptors in perfused liver of
      ovariectomized rats.
AB  - The experiments were carried out on ovariectomized Wistar rats. Their livers were
      perfused with basic perfusion medium (BPM) or BPM supplemented with isoflavone
      genistein, insulin or combination of the two factors. The obtained results
      support the hypothesis that genistein influences the kinetics of insulin binding
      to cell membranes changing the number of insulin receptors and dissociation
      constant (Kd). BPM supplementation with genistein decreased number of high
      affinity insulin receptors (HAIR) both in livers treated and untreated with
      insulin. The amount of HAIR diminished significantly from 610 +/- 77 x 10(-15)
      (no genistein) to 238 +/- 72 x 10(-15) mol/mg of membrane protein (supplement of
      genistein). Similarly, genistein reduced slightly the amount of HAIR even when
      added together with insulin (372 +/- 59 x 10(-15) mol/mg) in comparison to rats
      perfused with medium containing insulin but not the isoflavone (421 +/- 46 x 10(
      15) mol/mg). Simultaneously, genistein decreased significantly Kd for HAIR
      (perfusion with BPM--1.44 +/- 0.18 x 10(-9) mol/l; perfusion with BMP + genistein
      -0.83 +/- 0.20 x 10(-9) mol/l). Such effects of genistein during liver perfision
      did not take place when the liver membranes were in vitro incubated with this
      xenobiotic.

PMID- 10071765
TI  - Characterization of ligand-induced conformational states in the beta 2 adrenergic
      receptor.
AB  - Drugs acting at G protein coupled receptors can be classified in biological
      assays as either agonists, partial agonists, neutral antagonists, or as inverse
      agonists. Very little is known about the actual molecular events and structural
      changes that occur in the receptor following ligand binding and during
      transmission of a signal across the membrane. Therefore, the structural basis for
      the biological classification of drug action remains unknown. To date, the
      conformational state of G protein coupled receptors has been inferred from the
      activity of the effector enzyme modulated by the G protein. We have used two
      different approaches to monitor conformational changes in beta 2 adrenergic
      receptor. Fluorescence spectroscopy can be used to directly monitor structural
      changes in purified beta 2 adrenergic receptor in real-time. The emission from
      many fluorescent molecules is strongly dependent on the polarity of the
      environment in which they are located. Thus, fluorescent probes covalently bound
      to proteins can be used as sensitive indicators of conformational changes and
      protein-protein interactions. In addition, we examined functional differences
      between agonists and partial agonists using fusion proteins between wild-type
      beta 2 receptor or a constitutively active beta 2 receptor mutant and Gs alpha.
      These receptor-G protein fusion proteins guarantee highly efficient coupling with
      a defined stoichiometry. The results of these experiments will be discussed in
      the context of current models of G protein coupled receptor activation.

PMID- 10071766
TI  - Agonist-specific regulation of delta-opioid receptor trafficking by G protein
      coupled receptor kinase and beta-arrestin.
AB  - Opioid receptors mediate multiple biological functions through their interaction
      with endogenous opioid peptides as well as opioid alkaloids including morphine
      and etorphine. Previously we have reported that the ability of distinct opioid
      agonists to differentially regulate mu-opioid receptor (mu OR) responsiveness is
      related to their ability to promote G protein-coupled receptor kinase (GRK)
      dependent phosphorylation of the receptor (1). In the present study, we further
      examined the role of GRK and beta-arrestin in agonist-specific regulation of the
      delta-opioid receptor (delta OR). While both etorphine and morphine effectively
      activate the delta OR, only etorphine triggers robust delta OR phosphorylation
      followed by plasma membrane translocation of beta-arrestin and receptor
      internalization. In contrast, morphine is unable to either elicit delta OR
      phosphorylation or stimulate beta-arrestin translocation, correlating with its
      inability to cause delta OR internalization. Unlike for the mu OR, overexpression
      of GRK2 results in neither the enhancement of delta OR sequestration nor the
      rescue of delta OR-mediated beta-arrestin translocation. Therefore, our findings
      not only point to the existence of marked differences in the ability of different
      opioid agonists to promote delta OR phosphorylation by GRK and binding to beta
      arrestin, but also demonstrate differences in the regulation of two opioid
      receptor subtypes. These observations may have important implications for our
      understanding of the distinct ability of various opioids in inducing opioid
      tolerance and addiction.

PMID- 10071767
TI  - Phosphorylation and recycling kinetics of G protein-coupled receptors.
AB  - The rate of ligand-induced phosphorylation of the V2 and V1a vasopressin
      receptors was characterized in HEK 293 cells. Both receptors were phosphorylated
      predominantly by GRKs, and the V1a receptor was also phosphorylated by protein
      kinase C regardless of the presence or absence of ligand. Phosphorylation of the
      V1aR catalyzed by GRKs reached maximal values at the shortest measured time: 15
      seconds, and decayed rapidly with a t1/2 of 6 min in the continuous presence of
      AVP. In agreement with the hypothesis that dephosphorylation must precede
      receptor recycling to the cell surface, the V1aR returned rapidly to the cell
      surface after removal of the hormone from the medium. Phosphate incorporation
      into the V2R proceeded at a slower pace, and the internalized phosphorylated
      receptor failed to recycle to the cell surface and retained its phosphate for a
      long time in the presence or absence of ligand. A single mutation in the carboxy
      terminus of the V2R accelerated de-phosphorylation of the protein and conferred
      recycling properties to the V2R. These experiments provided molecular evidence
      for the hypothesis that internalization is required for de-phosphorylation and
      recycling of reactivated G protein coupled receptors to the cell surface.

PMID- 10071768
TI  - The uncoupled state of the human formyl peptide receptor.
AB  - The formyl peptide receptor (FPR) has been widely used to study the kinetics of
      the interaction between ligand, receptor and G protein with real-time
      fluorescence methods. Because the wild type receptor rapidly signals, and is then
      desensitized and internalized once occupied by ligand, it has been difficult to
      study the uncoupled receptor form. We have examined a mutant form of the FPR
      expressed in U937 cells that does not bind G protein and is thus ideal to study
      the uncoupled form of the FPR in the intact cell. Using kinetic flow cytometry,
      we have measured the dissociation kinetics of a fluorescent ligand from this
      mutant in intact, permeabilized and fixed cells. We observed a novel uncoupled
      receptor form in the intact cell with a dramatically reduced off-rate
      (approximately 0.02 s-1) from LR in a broken cell preparation (approximately 0.2
      s-1). Both receptor forms are retained in the presence of formaldehyde. We also
      observed this novel receptor form coexisting with the LRG complex when the wild
      type receptor is fixed in neutrophils or transfectants. These results complex
      when the wild type receptor is fixed in neutrophils o transfectants. These
      results lead us to suggest that there are distinct receptor structures in cells
      and membranes and that only a fraction of receptors in intact cells exist in the
      uncoupled form.

PMID- 10071769
TI  - Molecular modelling studies on G protein-coupled receptors: from sequence to
      structure?
AB  - In pharmaceutical research G protein-coupled receptors (GPCR) emerged as a
      superfamily of prominent drug targets. Extensive protein sequence analyses on
      GPCRs revealed a common protein topology consisting of a membrane-spanning seven
      helix bundle, which is believed to accommodate the binding site for low-molecular
      weight ligands. Enormous efforts are undertaken to generate GPCR structural
      models by means of molecular modelling, since these have already been shown to
      aid the process of lead structure finding and optimisation in that they provide
      atomistic models for structure-based drug design approaches. One of the most
      critical steps in modelling the transmembrane domains of GPCRs is the assignment
      of the putative transmembrane sequence stretches from multiple protein sequence
      alignment analyses. This study focuses on the comparative evaluation of protein
      sequence analysis tools, such as periodicity analyses, multiple sequence analyses
      or directional helix descriptors, especially developed for modelling the 7TM
      domains of GPCRs. In this context we will demonstrate that from application of
      different methods contradictory results can be obtained for the identification of
      the putative transmembrane sequence stretches of peptide-binding GPCRs, as
      exemplified with a comprehensive protein sequence analysis study based on the
      most prominent members of that receptor class (angiotensin II, CCK/gastrin,
      interleukin 8, endothelin, etc.).

PMID- 10071770
TI  - Molecular dynamics of a vasopressin V2 receptor in a phospholipid bilayer
      membrane.
AB  - Molecular dynamics simulations were carried out for a V2 receptor (V2R) model
      embedded in a dimyristoylphosphatidylcholine (DMPC) bilayer. Both free and ligand
      bound states of V2R were modeled. Our initial V2R model was obtained using a rule
      based automated method for GPCR modeling and refined using constrained simulated
      annealing in vacuo. The docking site of the native vasopressin ligand was
      selected and justified upon consideration of ligand-receptor interactions and
      structure-activity data. The primary purpose of this work was to investigate the
      usefulness of MD simulation of an integral membrane protein like a GPCR receptor,
      upon inclusion of a carefully parameterized surrounding lipid membrane and water.
      Physical properties of the system were evaluated and compared with the fully
      hydrated pure DMPC bilayer membrane. The solvation interactions, individual lipid
      protein interaction and fluctuations of the protein, the lipid, and water were
      analyzed in detail. As expected, the membrane-spanning helices of the protein
      fluctuate less than the peripheral loops do. The protein appears to disturb the
      local lipid structure. Simulations were carried out using AMBER 4.1 package upon
      constant number-pressure-temperature (NPT) conditions on massively parallel
      computers Cray T3E and IBM SP2.

PMID- 10071771
TI  - Expression of the alpha 1b-adrenergic receptor and G protein subunits in
      mammalian cell lines using the Semliki Forest virus expression system.
AB  - Semliki Forest virus (SFV) vectors have been efficiently used for rapid high
      level expression of several G protein-coupled receptors. Here we describe the use
      of SFV vectors to express the alpha 1b-adrenergic receptor (AR) alone or in the
      presence of the G protein alpha q and/or beta 2 and gamma 2 subunits. Infection
      of baby hamster kidney (BHK) cells with recombinant SFV-alpha 1b-AR particles
      resulted in high specific binding activity of the alpha 1b-AR (24 pmol
      receptor/mg protein). Time-course studies indicated that the highest level of
      receptor expression was obtained 30 hours post-infection. The stimulation of BHK
      cells, with epinephrine led to a 5-fold increase in inositol phosphate (IP)
      accumulation, confirming the functional coupling of the receptor to G protein
      mediated activation of phospholipase C. The SFV expression system represents a
      rapid and reproducible system to study the pharmacological properties and
      interactions of G protein coupled receptors and of G protein subunits.

PMID- 10071772
TI  - Comparison of antibodies directed against receptor segments of NPY-receptors.
AB  - The Y1-, Y2-, Y4- and Y5-receptor, which belong to the rhodopsin-like G-protein
      coupled, 7 transmembrane helix spanning receptors, bind the 36-mer neuromodulator
      NPY (neuropeptide Y) with nanomolar affinity. Synthetic fragments of the second
      (E2) and third (E3) extracellular loop were used to generate subtype selective
      anti-receptor antibodies against the Y-receptors. As investigated on intact
      receptors by ELISA and on solubilized receptors by SDS-PAGE and subsequent
      Western blotting, subtype selectivity was only partly achieved. Nevertheless,
      selectivity can be obtained by using several antisera in combination. These
      antibodies represent tools for molecular mass determination, receptor
      purification by affinity chromatography with antibody-columns and receptor
      localization studies.

PMID- 10071773
TI  - Development of a dual glow-signal firefly and Renilla luciferase assay reagent
      for the analysis of G-protein coupled receptor signalling.
AB  - Several reporter gene assays have been described where gene transcription is
      activated as a consequence of a specific signal transduction event, such as
      activation of adenylyl cyclase (1.2). Reporter genes typically consist of
      specific responsive elements placed upstream of a minimal promoter, which
      together control the expression of a readily detectable reporter protein, such as
      luciferase. We have developed a dual glow-signal firefly and Renilla luciferase
      assay, which allows the simultaneous measurement of two reporter genes in the
      same well of a 96-well plate. In this report we demonstrate the use of this assay
      for the simultaneous analysis of agonist activity at two G-protein coupled
      receptors which signal through activation of the G-protein alpha sub-unit, G
      alpha S. Chinese hamster ovary (CHO) cells stably transfected with a cAMP
      responsive firefly luciferase reporter were further transfected with the human
      Vasopressin V2 receptor. Similarly, CHO cells stably transfected with a cAMP
      responsive Renilla luciferase reporter were further transfected with the human
      beta 2-adrenoceptor. The two cell lines were mixed in individual wells of a 96
      well plate and a number of compounds were screened to determine their activity at
      both receptors. Stimulation with vasopressin and beta 2-adrenoceptor agonists
      resulted in the activation of the firefly and Renilla luciferases respectively.
      Stimulation with forskolin, which directly stimulates adenylyl cyclase, caused
      the activation of both reporter genes, and stimulation with a range of further
      compounds with no activity at either receptor did not generate a reporter
      response. The dual luciferase assay allows the simultaneous screening of two
      receptors in a 96-well format resulting in significant time and cost savings.

PMID- 10071774
TI  - Synthesis and characterization of new radioligands for the mammalian melanin
      concentrating hormone (MCH) receptor.
AB  - Melanin-concentrating hormone (MCH) is a neuropeptide present in the brain of all
      vertebrates. For the characterization of MCH receptors, a monoiodinated [Phe13,
      Tyr19]-MCH radioligand analogue was developed. The high susceptibility of [125I]
      [Phe13, Tyr19]-MCH to oxidative damage and its very lipophilic nature made it
      necessary to develop new MCH radioligands. To increase the stability, native
      methionines were replaced by non-sulphur containing amino acid residues. In one
      analogue, the L-enantiomer of the phenylalanine residue at position 13 was
      substituted by the D-enantiomer, which increased the relative affinity of the
      ensuing [125I]-[D-Phe13, Tyr19]-MCH about 7-fold. The different analogues were
      iodinated by an enzymatic reaction and used for binding studies with mouse
      melanoma cells. [125I]-[Met(O)4,8, Phe13, Tyr19]-MCH and [125I]-[Hse4,8, Phe13,
      Tyr19]-MCH showed only about 19% of total binding and [125I]-[Ser4,8, Phe13,
      Tyr19]-MCH displayed about 44% of total binding when compared with [125I]-[Phe13,
      Tyr19]-MCH. Non-specific binding for all tracers was below 11% of total binding
      of [125I]-[Phe13, Tyr19]-MCH binding. [125I]-[D-Phe13, Tyr19]-MCH was used for
      saturation binding studies and revealed a KD of 122.7 +/- 15.3 pmol/l. This
      radioligand was further characterized by association and dissociation binding
      studies.

PMID- 10071775
TI  - Fluorescent muscarinic EGFP-hM1 chimeric receptors: design, ligand binding and
      functional properties.
AB  - We describe the construction, expression and characterization of recombinant
      proteins comprising the enhanced green fluorescent protein (EGFP) fused to the
      amino-terminal part of the muscarinic hM1 receptor together or not with an
      additional hexahistidine tag placed at the C-terminal end of the receptor.
      Expression of the fluorescent proteins reaches levels identical to those of the
      wt hM1 receptor, provided that fusion takes place at the very N-terminal end of
      the receptor. Also correct protein folding and targeting to plasma membrane is
      obtained upon addition of a signal peptide promoting amino-terminal domain
      translocation through the membrane. Ligand binding properties of--and activation
      of the calcium release response by--the fusion proteins are almost identical to
      those of the wild-type muscarinic receptor, indicating that such fluorescently
      labelled receptors are valuable model systems for further functional, biochemical
      and structural studies.

PMID- 10071776
TI  - Steady-state binding of adenine nucleotides ATP, ADP and AMP to rat liver and
      adipose plasma membranes.
AB  - Binding of native adenine nucleotides to rat liver and adipose plasma membranes
      was studied under steady-state conditions using EDTA/Na for inhibition of ecto
      nucleotidase activity. [3H]-labelled ATP, ADP and AMP are able to interact with
      specific binding sites with respective Kd values of 88 +/- 9, 278 +/- 29 and 495
      +/- 40 nmol/l for liver membranes; and of 64 +/- 7, 231 +/- 36 and 2050 +/- 290
      nmol/l for adipose membranes. The nucleotide-binding capacity (Bmax) varied from
      15 to 18 pmol/mg protein in the case of [3H]ATP and [3H]ADP-binding studies and
      from 22 to 26 pmol/mg protein for [3H]AMP-binding sites. Both 2-MeSATP and ADP
      inhibited [3H]ATP-binding to membranes with respective IC50 values of 60 +/- 7
      and 285 +/- 30 nM. Other purinergic agents suramin, Reactive blue 2, alpha,beta
      MeATP and beta,gamma-MeATP were less potent competitors of [3H]ATP binding,
      whereas AMP, adenosine, GTP, UTP, and CTP did not cause any displacement effect
      at concentrations of 10(-6)-10(-5) M. It is suggested that the described ATP/ADP
      binding sites are linked to G protein-coupled P2Y receptors, whereas AMP-binding
      sites may represent a substrate-binding component of the membrane ecto-5'
      nucleotidase.

PMID- 10071777
TI  - A combinatorial peptoid library for the identification of novel MSH and
      GRP/bombesin receptor ligands.
AB  - A tripeptoid library was synthesized using 69 different primary amines in
      initially 69 individual reactions by the mix and split approach. The resulting
      library consisted of 328,509 (69(3)) single compounds, divided in 69 subpools
      each containing 4,761 entities. The 69 subpools were tested in two binding
      assays, one for alpha-MSH (alpha-melanotropin) and one for GRP (gastrin-releasing
      peptide)/bombesin. The sublibraries with the highest affinity to the MSH receptor
      (i.e. melanocortin type 1 or MC1 receptor) and, respectively, the GRP-preferring
      bombesin receptor were identified by an iterative process. Individual tripeptoids
      with good binding activity were resynthesized, analyzed and their dissociation
      constants and biological activity determined. The KD of the most potent MC1
      receptor ligand was 1.58 mumol/l and that of the GRP-preferring bombesin receptor
      3.40 mumol/l. Extension of this latter tripeptoid structure whose KD value
      increased to 280 nmol/l. A similar increase in activity was not observed with the
      most potent MSH tripeptoid ligand when extended by one residue, but a compound
      suitable for radioiodination and lacking the N-terminal amino group had a
      slightly higher binding activity than the tripeptoids (KD approximately 850
      nmol/l). These results demonstrate that testing a peptoid library containing
      328,509 single compounds led to the successful identification of new ligands for
      both the MC1 receptor as well as the GRP-preferring bombesin receptor.

PMID- 10071778
TI  - Synthesis and receptor binding analysis of thirteen oligomeric alpha-MSH analogs.
AB  - Thirteen oligomeric analogs from dimers up to a hexamer of alpha-melanocyte
      stimulating hormone (alpha-MSH) were synthesized and tested on melanoma cells for
      their ability to bind to melanocortin type 1 (MC1) receptors and to stimulate
      melanin production in the cells. The peptidic oligomers were made by linking
      several copies of the alpha-MSH fragment analog Nle-Asp-His-[D-Phe]-Arg-Trp-Lys
      NH2 to different templates through formation of oxime bonds. They were found to
      have binding affinities at 37 degrees C up to 8 times higher and melanogenesis
      inducing activities up to 4 times higher than those of the native hormone. At 15
      degrees C, one dimer showed a binding affinity 20 times higher than that of alpha
      MSH. These results are discussed in terms of possible bridging of neighboring
      receptors which has been suggested to occur in some other systems.

PMID- 10071779
TI  - Calcium signalling and gene expression.
AB  - A wide variety of compounds acting as extracellular signals cause changes in the
      free cytosolic Ca2+ concentration. These factors include hormones, growth
      factors, neurotransmitters, but also nutrient and metabolic activators. Ca2+
      signalling is caused by mobilization of Ca2+ from internal stores and by well
      controlled and timed Ca2+ influx from the extracellular space. Ca2+ signals
      address Ca2+ dependent enzymes, most importantly Ca2+ sensitive protein kinases
      and phosphatases. The profound influence of Ca2+ signalling on gene expression
      has been recognized a long time ago. As Ca2+ signals are short-lived when
      compared to alterations in differentiated gene expression, it is generally
      considered that genes coding for short-lived transcription factors (i.e. fos,
      jun) are the immediate target of Ca2+ signalling. Transcription of these
      immediate early genes (IEG) can be activated without the need for protein
      synthesis. Ca2+ signalling affects differentiated gene expression via changes in
      the absolute and relative abundance of IEG products, which in turn control the
      expression of differentiated genes. Ca2+ signals can stimulate both
      transcriptional initiation as well as transcriptional elongation. Initiation of
      transcription is stimulated by the Ca2+ dependent phosphorylation of binding
      proteins addressing two response elements in the promoter of IEGs: the cAMP
      response element, CRE, and the serum response element, SRE. Distinct protein
      kinases are involved in either case. We study the elongation of transcripts of
      the IEG c-fos beyond the first intron which is favoured by Ca2+ signals,
      involving mechanisms which still are poorly understood. We can show that intron
      sequences contribute to the control of elongation by Ca2+, and that there is a
      strong interrelation between the transcription control by the promoter and by the
      intron.

PMID- 10071780
TI  - Blue native PAGE as a useful method for the analysis of the assembly of distinct
      combinations of nicotinic acetylcholine receptor subunits.
AB  - Oligomerization of complete and incomplete combinations of rat muscle-type
      nicotinic acetylcholine receptor (nAChR) subunits in Xenopus oocytes was studied
      by blue native PAGE and compared with acetylcholine-activated current in these
      cells. The rank order of expression level judged by current was alpha 1 beta 1
      gamma delta >> alpha 1 beta 1 gamma > alpha 1 beta 1 delta > alpha 1 gamma delta
      >> alpha 1 delta >> alpha 1 gamma. alpha 1 and alpha 1 beta 1 were not
      functional. Protein complexes incorporating a heptahistidyl-tagged alpha 1
      subunit were chromatographically purified from digitonin extracts of oocytes and
      resolved by blue native PAGE. In the absence of any co-expressed nAChR subunit,
      the majority of alpha 1 formed aggregates. Co-expression of beta 1 had no effect
      on alpha 1 aggregation, whereas both gamma and delta diminished alpha 1
      aggregation in favor of discrete oligomers: alpha 1 formed tetramers together
      with gamma and dimers, trimers, and tetramers together with delta. When alpha 1
      gamma was complemented with beta 1 to form a functional alpha 1 beta 1 gamma
      receptor, a small amount of a pentamer was found besides a prominent alpha 1-His7
      beta 1 gamma trimer. Expression of the functional alpha 1 beta 1 delta receptor
      yielded marked amounts of a pentamer besides dimers and trimers. These results
      are discussed in terms of the assembly model of Green and Claudio (Cell 74, 57
      69, 1994), substantiating that blue native PAGE is suited for the investigation
      of ion channel assembly.

PMID- 10071781
TI  - Angiotensin II type 1 receptor activation modulates L- and T-type calcium channel
      activity through distinct mechanisms in bovine adrenal glomerulosa cells.
AB  - In adrenal zona glomerulosa cells, calcium entry is crucial for aldosterone
      production and secretion. This influx is stimulated by increases of extracellular
      potassium in the physiological range of concentrations and by angiotensin II (Ang
      II). The high threshold voltage-activated (L-type) calcium channels have been
      shown to be the major mediators for the rise in cytosolic free calcium
      concentration, [Ca2+]c, observed in response to a depolarisation by physiological
      potassium concentrations. Paradoxically, both T- and L-type calcium channels have
      been shown to be negatively modulated by Ang II after activation by a sustained
      depolarisation. While the modulation of T-type channels involves protein kinase C
      (PKC) activation, L-type channel inhibition requires a pertussis toxin-sensitive
      G protein. In order to investigate the possibility of additional modulatory
      mechanisms elicited by Ang II on L-type channels, we have studied the effect of
      PKC activation or tyrosine kinase inhibition. Neither genistein or MDHC, two
      strong inhibitors of tyrosine kinases, nor the phorbol ester PMA, a specific
      activator of PKC, affected the Ang II effect on the [Ca2+]c response and on the
      Ba2+ currents elicited by cell depolarisation with the patch-clamp method. We
      propose a model describing the mechanisms of the [Ca2+]c modulation by Ang II and
      potassium in bovine adrenal glomerulosa cells.

PMID- 10071782
TI  - Synthesis and electrophysiological studies of a novel epibatidine analogue.
AB  - The new epibatidine analogue exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (2PABH)
      was synthesised. Separation of enantiomers was performed on chiral HPLC
      chromatography in polar-organic phase mode at 0 degree C. Enantiomeric purity was
      greater than 99.8%ee for the (-)- and 90.5%ee for the (+)-enantiomer
      respectively. Optical rotation was determined to be [alpha]23D = +/- 13 degrees.
      Electrophysiological studies of 2PABH were carried out on alpha 4 beta 2, alpha 3
      beta 4 and alpha 7 nAChR subtypes cloned from rat and reconstituted in Xenopus
      oocytes. Both enantiomers could not significantly activate the heteromeric
      subtypes. The homomeric alpha 7 nAChR displays a high sensitivity only towards (
      )-2PABH. The EC50 for (-)-2PABH and ACh were determined (32.5 +/- 9.5 microM,
      137.3 +/- 16.5 microM). (-)-2PABH was shown to be a partial agonist (80% of ACh).
      Thus the efficacy of 2PABH differs markedly from that of epibatidine. The
      intramolecular N-N-distance and the spatial pyridine nitrogen orientation play a
      central role in nAChR recognition.

PMID- 10071783
TI  - Fluorescence techniques for fundamental and applied studies of membrane protein
      receptors: the 5-HT3 serotonin receptor.
AB  - A fluorescently labelled ligand for the 5-HT3 serotonin receptor was synthesised
      and its sub-nanomolar affinity for the purified, detergent solubilised receptor
      was measured. The change in the ligand's fluorescence upon receptor binding was
      used to directly measure its dissociation constant for receptor binding, to
      determine the pharmacology of the receptor, and finally to characterise the
      binding site of the receptor. A total internal reflection fluorescence (TIRF)
      assay for the 5-HT3 receptor was developed, which is suitable for high-through
      put screening. Therefore, the receptor was immobilised via its C-terminal His-tag
      onto a nitrilotriacetic acid-modified quartz surface. The affinities of both the
      fluorescent ligand and several non-fluorescent compounds were rapidly determined
      by the TIRF assay, and were shown to agree well with both the solution and
      classical radioligand binding assays. This indicated that the functional
      integrity of the receptor was preserved at the sensor surface. Due to the extreme
      sensitivity of the TIRF assay allows to obtain a complete pharmacological
      affinity profile of a quantity of receptor provided by a small number of highly
      expressing cells.

PMID- 10071784
TI  - Reactive affinity probes for the mapping of the glycine-binding site of the NMDA
      receptor NR1 subunit.
AB  - The glycine co-agonist binding site of the NMDA receptor is a target for the
      prevention and treatment of neurotoxic and neurodegenerative conditions. Until
      now, the interactions taking place at this site, and its structure, have been
      investigated by ligand structure-activity relationships and by site-directed
      mutagenesis. On the basis of a structural model which is currently proposed for
      this site, we have designed and synthesized six affinity markers by substituting
      electrophilic reactive groups in the 4, the 7 and the 3' positions of L 701,324,
      a high-affinity glycine site antagonist. These compounds compete with 3H-DCKA
      binding to rat brain membranes at equilibrium with nanomolar to low-micromolar
      affinities, and antagonize glycine-evoked currents in oocytes transfected with
      wild-type NR1-NR2B. However, they do not induce a time-shift in binding
      equilibria, and do not inactivate irreversibly the glycine evoked currents. Since
      they react only with cysteine at physiological pH, we conclude that there is no
      such residue in the site, in agreement with the model. Our affinity markers
      therefore represent potential topological probes for NMDA receptors with sequence
      positions related to the glycine-binding site mutated into cysteine.

PMID- 10071785
TI  - Benzophenone-type photoactivatable derivatives of alpha-neurotoxins and alpha
      conotoxins in studies on Torpedo nicotinic acetylcholine receptor.
AB  - By chemical modification of different lysine residues, benzoylbenzoyl (BzBz)
      groups were introduced into neurotoxin II Naja naja oxiana (NT-II), a short-chain
      snake venom alpha-neurotoxin, while p-benzoylphenylalanyl (Bpa) residue was
      incorporated in the course of peptide synthesis at position 11 of alpha-conotoxin
      G1, a neurotoxic peptide from marine snails. Although the crosslinking yields for
      iodinated BzBz derivatives of NT-II and for Bpa analogue of G1 to the membrane
      bound Torpedo californica nicotinic acetylcholine receptor (AChR) are relatively
      low, the subunit labeling patterns confirm the earlier conclusions, derived from
      arylazide or diazirine photolabels, that alpha-neurotoxins and alpha-conotoxins
      bind at the subunit interfaces. Detecting the labeled alpha-subunit with
      iodinated Bpa analogue of G1 provided a direct proof for the contact between this
      subunit and alpha-conotoxin molecule.

PMID- 10071786
TI  - Subtleties of structure-agonist versus antagonist relationships of opioid
      peptides and peptidomimetics.
AB  - The development of novel delta opioid antagonists and delta opioid agonists
      structurally derived from the prototype delta antagonist TIPP (H-Tyr-Tic-Phe-Phe
      OH), is reviewed. Both delta antagonists and delta agonists with extraordinary
      potency and unprecedented delta receptor selectivity were discovered. Some of
      them are already widely used as pharmacological tools and are also of interest as
      potential therapeutic agents for use in analgesia. The results of the performed
      structure-activity studies revealed that the delta antagonist versus delta
      agonist behavior of this class of compounds depended on very subtle structural
      differences in diverse locations of the molecule. These observations can be best
      explained with a receptor model involving a number of different inactive and
      active receptor conformations.

PMID- 10071787
TI  - Functional architecture of vasopressin/oxytocin receptors.
AB  - Three-dimensional models of G protein-coupled receptors (GPCR) have been defined
      using most experimental data available and protein modeling techniques. The
      endogenous ligand binding sites have been qualitatively described and putative
      receptor activation mechanisms have been proposed. The model has been recently
      refined to take into account recent crystallographic data. Most experimental
      results published are in excellent qualitative agreement with the initial model.
      We have undertaken to study more systematically by site directed mutagenesis the
      vasopressin/oxytocin receptor binding domain as a prototype of neuropeptide
      receptors. The experimental results are in very good agreement with the models.
      The residues responsible for the neuropeptide binding have been identified and
      confirm the predicted localization of the neuromediator in the transmembrane
      domain of the receptors. The side chain of the 8th residue of vasopressin
      interacts with a non-conserved receptor residue located in the first
      extracellular loop. As predicted from the model, this interaction is completely
      responsible for the selectivity of the ligand-receptor interaction. Finally,
      aromatic residues which allow the modulation of the efficacy of agonists have
      been identified.

PMID- 10071788
TI  - Partial agonism: mechanisms based on ligand-receptor interactions and on stimulus
      response coupling.
AB  - Substances eliciting, at very high concentrations, a lower maximal response of a
      particular biological system than a defined standard, are defined as partial
      agonists. The convention rests on the definition of a standard substance that
      achieves a 'full' maximal response; partial agonism being, therefore, relative.
      Various mechanisms lie behind this phenomenon: 1. Receptor-related mechanisms:
      the agonist-receptor complex exists in several conformational states from which
      only one, or only a few, activate the cell signaling pathway. This may occur when
      the receptor itself, or the agonist, exists in multiple states (e.g., in the form
      of enantiomers or stereoisomers), or when the agonist-receptor complex changes
      its conformation (receptor switch: two-state model of receptor activation).
      Furthermore, a steric hindrance by a 'wrong-way binding' of a part of the
      agonist's molecules may prevent the full 'correct' occupancy of receptors. 2.
      Mechanisms based on the efficacy of the stimulus-response coupling. The efficacy
      is then proportional to the sum of probabilities that receptors in individual
      states activate the cell-signaling pathway. Doses (concentrations) eliciting the
      half maximal response (EC50), or similar response sensitivity parameters, are not
      included in the definition of partial agonism. However, tight correlations exist
      between maximal response and EC50 in many, but not all, generic groups of
      agonistically acting substances. These relationships are frequently linear;
      intercepts and slopes of these 'E, KE plots' are characteristic for individual,
      putative mechanisms. Dose-response curves of partial agonists are akin to those
      obtained for a response to a full agonist after a stepwise partial inactivation
      of receptors by an irreversible inhibitor. Also, the E, KE plots obtained in
      these instances are similar to those of partial agonists. The receptor reserve,
      rather vaguely defined in early reports, is therefore closely linked to the
      phenomenon of partial agonism.

PMID- 10071789
TI  - Discovery and design of novel vasopressin hypotensive peptide agonists.
AB  - This presentation will trace the serendipitous discovery of novel vasopressin
      (VP) hypotensive agonists d(CH2)5[D-Tyr(Et)2,X3]VAVP (where X = Arg, Lys). These
      peptides were uncovered as part of an ongoing program aimed at the design of
      potent and selective VP antidiuretic (V2 receptor) antagonists. We will also
      present highlights of our subsequent preliminary studies seeking (i) to design
      high affinity radioiodinatable ligands for the localization and characterization
      of the putative VP vasodilatory (V1c?) receptor; (ii) to identify the structural
      features of selective and non-selective cyclic and linear VP and oxytocin (OT)
      antagonists of the V2 receptor, the vascular (V1a) receptor and of the uterine
      (OT) receptor required for hypotensive agonism and; (iii) to enhance hypotensive
      potency. These novel VP hypotensive agonists could serve as valuable research
      tools in studies on the roles of VP in blood pressure regulation and may also
      lead to the development of a new class of therapeutically useful
      antihypertensives.

PMID- 10071790
TI  - Structure-based design of nonnatural ligands for the HLA-B27 protein.
AB  - X-ray studies as well as structure-activity relationships indicate that the
      central part of class I MHC-binding nonapeptides represents the main interaction
      site for a T cell receptor. In order to rationally manipulate T cell epitopes,
      several nonpeptidic spacer have been designed from the X-ray structure of a MHC
      peptide complex and substituted for the T cell receptor-binding part of several
      antigenic peptides. The binding of the modified epitopes to the HLA-B*2705
      protein was studied by an in vitro stabilisation assay and the thermal stability
      of all complexes examined by circular dichroism spectroscopy. Depending on their
      chemical nature and length, the introduced spacers may be classified into two
      categories. Monofunctional spacers (11-amino undecanoate, (R)-3-hydroxybutyrate
      trimer) simply link two anchoring peptide positions (P3 and P9) but loosely
      contact the MHC binding groove, and thus decrease more or less the affinity of
      the altered epitopes to HLA-B*2705. Bifunctional spacers ((R)-3-hydroxybutyrate
      and beta-homoalanine combinations) not only bridges the two distant anchoring
      amino acids but also strongly interact with the binding cleft and lead to an
      increase in binding to the MHC protein. The presented modified ligands constitute
      interesting tools for perturbing the T cell response to the parent antigenic
      peptide.

PMID- 10071791
TI  - Use of mass spectrometric methods for protein identification in receptor
      research.
AB  - In recent years, mass spectrometry has become the method of choice for
      identifying small amounts of gel separated proteins. Using high mass accuracy
      peptide mass mapping followed if necessary by nanoelectrospray sequencing, most
      mammalian proteins can now be identified quickly and sensitively either in amino
      acid or in EST sequence databases. These methods are illustrated here using an
      ongoing project in the author's laboratory, a mass spectrometric screen for new
      mouse brain receptors and their interaction partners.

PMID- 10071792
TI  - Alphaviruses as tools in neurobiology and gene therapy.
AB  - The broad host range and superior infectivity of alphaviruses have encouraged the
      development of efficient expression vectors for Semliki Forest virus (SFV) and
      Sindbis virus (SIN). The generation of high-titer recombinant alphavirus stocks
      has allowed high-level expression of a multitude of nuclear, cytoplasmic,
      membrane-associated and secreted proteins in a variety of different cell lines
      and primary cell cultures. Despite the viral cytopathogenic effects, functional
      assays on recombinant proteins are possible for a time-period of at least 24
      hours post-infection. The high percentage (80-95%) of primary neurons infected
      with SFV has allowed localization and functional studies of recombinant proteins
      in these primary cell cultures. Through multiple infection studies the
      interaction of receptor and G protein subunits has become feasible. Establishment
      of efficient scale-up procedures has allowed production of large quantities of
      recombinant protein. Potential gene therapy applications of alphaviruses could be
      demonstrated by injection of recombinant SIN particles expressing beta
      galactosidase into mouse brain. Tissue/cell specific infection has been achieved
      by introduction of an IgG-binding domain of protein A domain into one of the
      spike proteins of SIN. This enabled efficient targeting of infection to human
      lymphoblastoid cells.

PMID- 10071793
TI  - Expression and intracellular localisation of odorant receptors in mammalian cell
      lines using Semliki Forest virus vectors.
AB  - Odorant receptors are members of the G protein-coupled receptor superfamily. They
      are expressed on the surface of cilia of olfactory neurons, where they bind
      ligand (odorant). Studies of the molecular mechanisms of olfaction are
      complicated by the extremely large number of receptor genes, and difficulties in
      pairing a particular mammalian receptor to a specific odorant ligand in vivo.
      Here we report expression and localisation studies of two rat odorant receptor
      genes (17 and OR5), and C. elegans odr-10, using the Semliki Forest virus (SFV)
      system. All receptors were epitope-tagged at the N- or C-terminus in order to
      facilitate their detection in infected cells, and determine the localisation and
      membrane-orientation of recombinant proteins. The immortalised mouse olfactory
      neuronal cell line OLF 442, rat cortical and striatal primary neuron cultures,
      and the baby hamster kidney (BHK) cells, were infected and tested.
      Immunofluorescence and confocal microscopy studies performed on permeabilised,
      non-permeabilised and native cells revealed that in BHK cells the rat receptors
      17 and OR5 were not targeted to the plasma membrane and remained in the
      endoplasmic reticulum. In contrast, in the mouse olfactory cell line OLF 442 both
      rat receptors were correctly inserted into the plasma membrane. Similar results
      were obtained using primary neurons, indicating that like mature neurons, the
      immortalised OLF 442 cells are capable of providing for correct odorant receptor
      processing and targeting.

PMID- 10071794
TI  - Enhanced metallosorption of Escherichia coli cells due to surface display of beta
      and alpha-domains of mammalian metallothionein as a fusion to LamB protein.
AB  - The lamB gene was inserted at with DNA fragments encoding N-terminal beta- and C
      terminal alpha-domains of human metallothionein 1A (HMT1A). The hybrid LamB
      proteins were expressed as full-length products. Virtually whole pool of hybrid
      LamB proteins was found localized in the outer membrane of E. coli to and cells
      expressing LamB variants retained sensitivity to lambda phage, indicating their
      correct folding. Expression of hybrid LamB proteins increased natural ability of
      E. coli accumulate bivalent heavy metals ions with the highest efficiency
      observed for cadmium. The order of amount of cadmium accumulated is alpha-domain
      of HMT1A > HMT1A >> beta-domain of HMT1A. This correlates with affinity for
      cadmium and stability of metallothionein and its individual domains. This
      confirms suitability of LamB vehicle for surface display of various bioactive
      molecules and suggests possibility of engineering of cell surface for
      bioremediation of heavy metals.

PMID- 10071795
TI  - Simple and fast method to test the receptor for advanced glycosylated endproducts
      (RAGE) for its tumor suppressive potential using the Tet-On system.
AB  - The Tet gene expression system, that allows tightly controlled gene expression in
      response to doxycycline, was applied to analyze the influence of the receptor for
      advanced glycosylation endproducts (RAGE) on the growth of 293 cells in semi
      solid medium. Establishing a Tet-On gene expression system involves two
      consecutive stable transfections. Here, we describe an alternative procedure to
      obtain a Tet-On gene expression system in a single transfection step for the use
      in tumor biology. The plasmids necessary for the regulated expression of RAGE
      together with the selectable marker plasmid were cotransfected in a molar ratio
      of 6:1. After aminoglycoside selection, 29 clones were analyzed using PCR
      revealing 8 colonies to be double stably transformed. Subsequent Western blot
      analysis showed inducible expression in 7 cell lines. Applying the one step
      protocol, the entire Tet-On expression system could be completed in half of the
      time required for the original two step method. The generated 293 double stable
      cells were used in the clonogenic assay for the testing of the tumor suppressive
      potential of RAGE.

PMID- 10071796
TI  - Characterization of transferrin receptor in an immortalized cell line of rat
      brain endothelial cells, RBE4.
AB  - The content and distribution of transferrin receptors in an immortalized cell
      line, RBE4, derived from rat cerebral capillary endothelial cells was
      investigated using the monoclonal antibody MRC OX-26 (OX-26 mAb) specific for the
      rat transferrin receptor. An ELISA assay was developed with which the OX-26 mAb
      can be determined quantiatively. The detection limit of the assay was 10 pg or
      0.07 fmol of murine antibody. With this technique accurate measurement of native
      antibody is now possible without the need for isotope labeling (iodination).
      Immunostaining of confluent monolayers of RBE4 cells using an antibody directed
      against the tight junction associated protein ZO-1 was indicative for structural
      intactness of RBE4 cell monolayers. OX-26 immunostaining demonstrated
      localization of the transferrin receptor at the plasma membrane and/or in the
      cytosol. Binding studies showed saturation of OX-26 mAb binding. The antibody
      binding analysis gave a dissociation constant (KD) of 17.1 +/- 1.2 nmol/l. The
      total amount of transferrin receptors present per cell was 70,800 +/- 17,000. Our
      results indicate that receptor binding of OX-26 mAb can be studied using an in
      vitro cell culture model of rat brain mircrovessel endothelium in conjunction
      with an ELISA technique for detection of native antibody. This approach will be
      used to investigate mechanisms of transendothelial transport of OX-26 in vitro.

PMID- 10071797
TI  - Specificity of signaling by hematopoietic cytokine receptors: instructive versus
      permissive effects.
AB  - The helical cytokines constitute a family of proteins with a common three
      dimensional structure. They exert a wide variety of biological effects with a
      preference for the hematopoietic system. The effects of helical cytokines are
      mediated by cell surface receptors, which belong to the cytokine receptor
      superfamily and signal by activating cytoplasmic tyrosine kinases of the Janus
      kinase (Jak) family and other downstream signaling pathways. The relevance of
      each of these pathways for eliciting a specific cellular response remains to be
      determined. This review will focus on cytokine receptors which play a role in the
      regulation of hematopoiesis and summarize data the address the question how
      specificity of signaling is achieved.

PMID- 10071798
TI  - A tribute to the Swiss receptor workshops and scientific meetings in general.

PMID- 10071799
TI  - Interactions between Helicobacter pylori and gastroesophageal reflux disease.

PMID- 10071800
TI  - Long esophagomyotomy for diffuse esophageal spasm and related disorders: an
      historical overview.
AB  - In summary, the role of long esophagomyotomy for patients with DES and related
      motor disorders remains controversial. The results are poorer than those
      following esophagomyotomy for achalasia, and long-term postoperative follow-up of
      these patients is essential because early good results may be misleading. Two
      methods are considered equally effective in avoiding postmyotomy reflux: a
      'short,' 'floppy' wrap of the LES, or a sphincter-sparing myotomy when manometry
      indicates normal functioning of the sphincter. Rarely is a total thoracic
      esophagomyotomy indicated. Because persistent or recurrent pain is the main cause
      of poor results, some patients may eventually require total esophagectomy and
      cervical esophagogastrostomy.

PMID- 10071801
TI  - The utility of the proliferative index in pretreatment biopsy specimens of
      esophageal squamous cell carcinoma.
AB  - The proliferative index detected immunohistochemically by monoclonal antibody MIB
      1 from pre-treatment biopsy tissues of 33 patients with esophageal squamous cell
      carcinoma who underwent preoperative concurrent chemoradiotherapy was evaluated
      in relation to clinicopathologic features and chemoradiotherapeutic responses.
      The response to chemoradiotherapy was assessed both endoscopically and
      pathologically and classified as complete or partial response. Higher MIB-1 LI
      was significantly associated with lymph node metastases, suggesting that
      detection of MIB-1 LI from biopsy tissues may contribute to pre-treatment staging
      of tumors and prediction of persistence of lymph node involvement after
      chemoradiotherapy, which would permit the optimization of systemic treatment for
      individual patients. Statistically, significant correlation existed between
      higher MIB 1-LI and poor overall survival, implicating the prognostic
      significance of the MIB-1 LI in patients undergoing multimodality treatment. No
      significant relationship was found between the MIB-1 LI and either endoscopic or
      pathologic responses, although a trend for tumors with lower MIB-1 LI to have
      better responses was observed.

PMID- 10071802
TI  - Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic
      esophagus according to biological markers.
AB  - We generally choose transhiatal esophagectomy (THE) for patients with high risk
      for postoperative complications and for carcinoma of the lower thoracic
      esophagus, even if the tumor is in the advanced stage. In order to define
      indications for THE in esophageal cancer patients, we investigated 40 THE cancer
      patients according to the expressions of EGF/EGFR, p53 and p21. In patients with
      stage I, II, III and IV tumors, 5-year survival rates were 66.7%, 28.6%, 30.0%
      and 11.4%, respectively. The sites of first recurrence were the lymph nodes (n =
      10) and single organs (n = 10). Dissemination (n = 3) and local recurrence (n =
      2) were also seen as a first recurrence. According to EGF/EGFR, 5-year survival
      rate was 69% and 14% in the low and high EGF/EGFR groups, respectively. According
      to p53 expression, 5-year survival was 60% and 30% in the negative and positive
      groups, respectively; according to p21 expression, 5-year survival was 71% and 0%
      in the negative and positive groups, respectively. Significant difference was
      seen in EGF/EGFR and p21 groups. These data support less invasive surgery for
      some patients even for esophageal cancer patients. THE is a less invasive
      surgery, that also implies fewer curative procedure. Our results also showed that
      THE alone will be the only curative procedure necessary for some patients. We can
      determine therapeutic procedures using these new factors, and thus avoid
      unnecessary excess surgical stress in esophageal cancer patients.

PMID- 10071803
TI  - Transhiatal esophagectomy for squamous cell carcinoma of the esophagus.
AB  - Eighty patients underwent transhiatal esophagectomy for squamous cell carcinoma
      of the esophagus. Dysphagia for solids was the presenting symptom in 90% of the
      patients. The standard technique of transhiatal esophagectomy was used and
      cervical anastomosis were hand sewn. The average operative time and blood loss
      were 190 min and 350 cc respectively. The 30 day mortality rate was 7.5% (six
      patients). Major respiratory complications were observed in 15 (18.7%) patients.
      Anastomotic leak rate was 10% (eight patients). The incidence of recurrent
      laryngeal nerve injury was 6.2% (five patients). The average hospital stay was 14
      days. Four patients had stage I, 30 had stage II and 46 had stage III disease.
      Forty-nine patients (60%) had lymph node involvement. The overall actual survival
      at 2 years was 55% and at 5 years was 37%. Of the operative survivors, 87%
      patients resumed normal swallowing and 10 patients (13.5%) required dilatation
      for anastomotic stricture. Transhiatal esophagectomy can be performed with low
      operative mortality, acceptable morbidity and offers good long-term functional
      results without compromising the survival of patients.

PMID- 10071804
TI  - The vascularization of a gastric tube as a substitute for the esophagus is
      affected by its diameter.
AB  - The stomach is used for reconstruction of the upper gastrointestinal tract after
      esophageal resection for cancer. The whole stomach can be used, but also a wide
      or narrow gastric tube can be constructed. Short-term functional results are
      superior after use of a narrow tube. Healing of the cervical esophagogastrostomy
      can be impaired, leading to leakage and stricture. The decreased vascularization
      at the site of the anastomosis may be one reason. It was hypothesized that the
      quality of the vascularization of the gastric tube, used as a substitute for the
      oesophagus after esophagectomy, depends on its diameter. The vascularization of
      postmortem specimens was studied using angiography. Whole stomachs (3), wide (3)
      and narrow gastric tubes (3) were constructed. In a patient with an anastomotic
      stricture of a narrow tube with a cervical esophagogastrostomy vascularisation
      was evaluated by angiography. After infusion of contrast through the supplying
      arteries, the whole stomachs and wide gastric tubes showed adequate
      vascularization, whereas the narrow gastric tube showed poor vascularization
      especially at the site of the anastomosis. In narrow gastric tubes, the right
      gastroepiploic artery was the only feeding artery. In the patient's angiography,
      a limited contrast visualization of the proximal end of the gastric tube could be
      demonstrated. Although a narrow gastric tube is favoured by some surgeons, the
      use of whole stomach or a type of gastric tube with preservation of the right
      gastric artery may lead to a better anastomotic healing.

PMID- 10071805
TI  - Fundoplication wrap disruption: an experimental study in rats.
AB  - Antireflux surgery usually gives long lasting control of gastroesophageal reflux
      disease, but late failures can occur from fundoplication wrap disruption.
      Disruption presumably occurs when physiological mechanical stresses cause the
      sutures to pull out of the fundoplication wrap. We hypothesized that complete
      fundoplications (fundus sutured to fundus) would withstand disruptive forces
      better than partial fundoplications (fundus sutured to esophagus). Forty-eight
      rats underwent fundoplication (24 partial and 24 complete). Fundoplication wraps
      were disrupted by distending the stomach (bursting pressure technique) and by
      distracting the wrap in a tensiometer (breaking strength technique). Bursting
      pressures were similar in the partial (103.7 +/- 13.5 mmHg) and complete (100.5
      +/- 13.1 mmHg) fundoplication wraps (P = 0.93, not significant). In both groups,
      all disruptions occurred by sutures tearing through the stomach wall. Breaking
      strength was also equivalent for the two types of wrap. Partial wraps disrupted
      at 6.69 +/- 1.49 N and complete wraps disrupted at 6.52 +/- 1.28 N (P = 0.77, not
      significant). Sutures tore out of the stomach side of the partial wrap in five
      rats and out of the esophagus in the other seven rats with partial wraps.
      Disruption occurred by sutures tearing through the stomach in all rats with
      complete fundoplications. This experimental study in the rat did not show any
      difference in the ability of partial and complete fundoplication wraps to
      withstand disruptive forces.

PMID- 10071806
TI  - Early cancer in achalasia.
AB  - Esophagus achalasia is considered by many authors a preneoplasic disease and, for
      this reason, they propose a follow-up with endoscopies and brush cytology. For
      others, the possibility of cancer in achalasia is very low and the surveillance
      is not justified owing to its fallibility and high cost. Generally, cancer in
      achalasia has a late diagnosis as a consequence of megaesophagus and of many
      years of symptoms attributed to achalasia disease. The rate of resectability is
      low and 5-year survival is very poor. To define the patients who have a high
      disease. The rate of resectability is low and 5-year survival is very poor. To
      define the patients who have a high risk of cancer in achalasia and to perform an
      early diagnosis is the challenge to improve resectability and to increase
      survival. The search of cancer in achalasia with endoscopies and lugol vital
      staining was performed in 18 out of 76 patients with achalasia. The 18 patients
      had enlarged esophagus and more than 10 years of evolution. Lugol negative
      endoscopic areas were found in 10 out of 18 patients and four out of 10 were
      carcinomas. Two were circular superficial erosive lesions (Tis N0 M0 and T1 N0
      M0), one was an elevated multifocal lesion of less than 1 cm diameter (T2 N0 M0)
      and the last one was a longitudinal central ulcer of less than 1 cm diameter (T1
      N0 M0). In the remaining 6 out of 10 patients the diagnosis was esophagitis. In
      the other 58 patients, three carcinomas were diagnosed, two advanced tumors, with
      endoscopy and biopsy (T3 and T4 N1) and the third one (T1 N0 M0) was a
      pathological finding in a resected specimen for recurrent achalasia and
      megaesophagus. The global prevalence was of 9.21% (7/76). The prevalence in
      advanced stages of achalasia was of 18.92% (7/37). The resectability rate was of
      85.71%. CONCLUSION: Achalasia patients with more than 20 years of evolution,
      enlarged esophagus with 'knees' and with marked retention must be considered to
      be of high risk for developing cancer. In this group, the surveillance with
      endoscopy and lugol vital staining or brush cytology is justified. Other common
      risk factors of esophageal cancer that must be considered are patients aged over
      60 years who are smokers and regular consumers of alcohol.

PMID- 10071807
TI  - Microbial flora of the normal esophagus.
AB  - The endogenous flora of the skin and some mucous membranes are well known,
      however, we were unable to find descriptions about normal esophageal flora in
      literature. We believe that knowledge about normal esophageal flora is important
      for therapeutic implications. We compiled data on 30 patients without infection
      of the oropharynx or esophagus who were admitted for an endoscopy of the upper
      digestive tract to determine normal esophageal flora. The samples were collected
      by injecting 10 ml of 0.9% physiological solution into the esophagus and
      oropharynx and removing it by suction. Esophageal samples from 30 patients and
      oropharingeal samples from 10 of these patients were collected. We identified
      mixed flora being Streptococcus viridans the most frequent microorganism found.
      Where samples from both the esophagus and oropharynx were collected, three
      occurrences of this same microorganism were found. We concluded that the
      isolation frequency of germs in the esophagus by the method used was high and the
      most frequently found germ was S. viridans. There is therefore a possible
      correlation between the flora from the oropharynx and the esophagus.

PMID- 10071808
TI  - Surgical treatment of Boerhaave's syndrome: when, how and why?
AB  - Ten cases of Boerhaave's syndrome have been treated in this hospital from 1983
      1998. Nine patients underwent surgery resulting in complete recovery in seven
      cases and two postoperative deaths. One was treated with a satisfactory outcome.
      Vomiting was considered to be the determinative factor for the illness in eight
      cases. The relationship between the rupture of the esophagus and vomiting and the
      mechanism of its occurrence based on anatomy and pathophysiology is discussed. It
      is believed that the most beneficial time to perform surgery is based on the
      general condition of the patient. The surgical procedure should consist of
      closure of the lacerated esophagus, a complete clearance of the fibrinous coating
      on the surface of the pleura, mobilization of a pedicled omentum pad and a
      gastrostomy. The chest should be entered from the side where the esophagus was
      lacerated or the X-ray examination showed hydrothorax or hydropneumothorax. The
      most important factor to guarantee a successful outcome for surgery is a complete
      clear off of the empyema and early expansion of the lung in addition to effective
      nutritional support.

PMID- 10071809
TI  - Dilatation therapy for dysphagia in patients with upper esophageal sphincter
      dysfunction--manometric and symptomatic response.
AB  - Inability to maintain oral nutrition due to oropharyngeal dysphagia is common in
      patients with a variety of neurological and neuromuscular disorders and severely
      affects quality of life. Cricopharyngeal dilatation has been used as empiric
      therapy in these patients, but little data exist on symptom response and there is
      no data on the effect on the manometric characteristics of the upper esophageal
      sphincter (UES) and pharynx. We studied 10 patients with oropharyngeal dysphagia
      and either elevated upper esophageal sphincter resting pressure, or a high
      residual pressure or attenuated duration of relaxation on swallowing. Dilatation
      therapy was performed with an 18-20 mm Savary dilator and manometry was repeated
      after an average period of 4 weeks. Nine out of 10 patients had improvement in
      dysphagia and have maintained oral nutrition for a mean follow-up of 13 months.
      UES residual pressure decreased in nine out of 10 patients and the group median
      value decreased significantly from 10.8 mmHg pretreatment to 5.7 mmHg after
      therapy (P < 0.05). UES resting pressure decreased in eight out of 10 patients
      and the group median value decreased from 82 to 43 mmHg (P < 0.05). Duration of
      relaxation did not change significantly. Videoradiography was normal in five out
      of nine responders to therapy. For selected patients with oropharyngeal dysphagia
      and manometric signs of UES dysfunction, dilatation therapy may give excellent
      symptomatic relief, apparently by reducing UES resting pressure and/or increasing
      the duration and completeness of relaxation.

PMID- 10071810
TI  - Laparoscopic cut Collis gastroplasty: a novel technique.

PMID- 10071811
TI  - Pedunculated esophageal leiomyosarcoma: a case report.
AB  - We report a case of esophageal leiomyosarcoma that possibly arose from the
      muscularis mucosae, thereby showing a particularly unusual appearance. A large
      polypoid intraluminal lesion in the distal esophagus was found on an endoscopic
      examination of a 68-year-old man with a 3-month history of dysphagia. Although
      the histological examination of biopsy specimens clearly revealed leiomyosarcoma,
      the absence of an exophytic component on computed tomography (CT) scan caused us
      to suspect that the tumor was carcinosarcoma. The tumor was resected by a
      subtotal esophagectomy. Microscopic evaluation revealed no involvement in the
      layer of the muscularis propria and no component of carcinoma. Clinical features
      of the pedunculated esophageal leiomyosarcoma shown in this case and three
      additional cases previously reported in the literature are reviewed.

PMID- 10071812
TI  - Synovial sarcoma of the esophagus simulating achalasia.
AB  - Synovial sarcoma is a rare malignancy occurring mainly in the extremities. Only
      seven cases have been described arising in the esophagus. All of them presented
      as a polypoid mass involving the upper third of the esophagus. A case of
      infiltrating synovial esophageal sarcoma simulating achalasia in a 63-year-old
      woman is reported. According to the literature, the location and the clinical
      pattern of this tumor are exceptional. The clinical features, pathologic
      findings, differential diagnosis, and management of this condition are discussed.

PMID- 10071813
TI  - Esophageal inflammatory pseudotumor associated with a pseudodiverticulosis cyst:
      two inter-related lesions?
AB  - There are some unusual esophageal lesions, which by their rarity, and location or
      etiology raise difficult therapeutic decisions for surgeons. In this report, we
      describe an esophageal inflammatory pseudotumor (IPT) associated with a
      pseudodiverticulosis cyst in an adult male. We discuss the pathogenic and the
      anatomopathological aspects of these uncommon associated lesions as well as the
      treatment of ITP.

PMID- 10071814
TI  - Omental wrapping of perforated esophagus.

PMID- 10071815
TI  - p53 gene mutation in 150 dissected lymph nodes in a patient with esophageal
      cancer.
AB  - For thoracic esophageal cancer, we perform extended three field lymph node
      dissection, and have achieved nearly 50% of overall 5-year survival. However,
      patients sometimes develop lymph node recurrences in spite of having no lymph
      node metastases found by conventional histopathologic examination. In a patient
      with esophageal squamous cell carcinoma, we sequenced all the p53 cDNA translated
      regions (exon 2-10) of primary carcinoma, and confirmed one p53 nonsense mutation
      in exon 10. Then we extracted genomic DNA from 150 surgically dissected lymph
      nodes from that patient, and performed polymerase chain reaction analysis (PCR
      RFLP) to detect the same p53 mutation in the lymph nodes. PCR-RFLP analysis
      showed the same p53 mutation in six lymph nodes. One node was located along the
      right recurrent laryngeal nerve, where no positive nodes was identified by
      conventional histopathologic examination. The p53 mutational diagnosis of
      metastatic cancer may be useful in detecting minimal residual disease.

PMID- 10071816
TI  - Curable cancer in a short segment Barrett's esophagus.

PMID- 10071817
TI  - Thermal behavior and dissolution properties of naproxen from binary and ternary
      solid dispersions.
AB  - Solid dispersions of 10% w/w naproxen (NAP) in poly(ethylene glycol) (PEG) (4000,
      6000, or 20,000) as a carrier with or without incorporation of anionic (sodium
      dodecyl sulfate; SDS) or nonionic (Tween 80; Tw80) surfactant were prepared by
      the melting method. Physicochemical characteristics were determined by
      differential scanning calorimetry (DSC) and X-ray diffraction analysis. The
      results of dissolution studies showed that drug dissolution properties were
      better from ternary systems than from binary systems since in the former the
      wetting and solubilizing effects of surfactant and polymer were additive. No
      influence of the PEG molecular weight was found. The best performance given by
      anionic surfactant has been attributed to several factors, such as higher
      hydrophilicity, better solubilizing power, and most facile interaction with both
      drug and PEG. No important changes in solid-state characteristics or in drug
      dissolution properties were found after 30 months storage for dispersions with or
      without surfactant. Only a slight decrease in initial drug dissolution rate was
      observed at the highest concentration (10% w/w) of SDS.

PMID- 10071818
TI  - Preparation and release of ibuprofen from polyacrylamide gels.
AB  - The conditions of preparation of polyacrylamide (polyAC) gels, the incorporation
      of ibuprofen (IB), and the kinetics of IB release under various conditions have
      been evaluated. Transparent, opaque, or elastic gels were prepared depending on
      the concentration of acrylamide (AC) and the cross-linking agent, N,N'
      methylenebisacrylamide (BIS). Release studies in media below pH 5.0 resulted in
      opaque gels. The kinetics of IB release was a function of the AC, BIS, and the pH
      of the medium, but the optimum composition, in terms of gel integrity and release
      characteristics, was 7% AC cross-linked with BIS at a 50:1 ratio. Modulation of
      the release rate was possible with the incorporation of 10% of certain polymers.
      The amount of IB that could be incorporated per gram of transparent gel was a
      function of the amount of polymer initiator N,N,N',N'-tetramethylene diamine
      (TEMED) used per gram of gel. More than 200 mg of IB could be incorporated per
      gram of transparent gel by using 100 microliters of TEMED. The release of IB
      obeyed matrix/swelling-controlled kinetics and 70-80% of the IB was released from
      gels containing 10 to 40 mg IB per gram of gel in 5 hr at pH 7.4 and 37 degrees
      C.

PMID- 10071819
TI  - Permeation of piroxicam from the poloxamer gels.
AB  - Topical formulations of piroxicam were prepared using poloxamer 407 or poloxamer
      188 by a cold method, and the permeation characteristics of piroxicam were
      evaluated. The permeation rate of piroxicam across the synthetic cellulose
      membrane and the rat skin decreased as the concentration of poloxamer increased.
      Though poloxamer gel exhibits reversed thermal behavior, the permeation rate of
      piroxicam increased with increasing temperature, indicating that the diffusional
      pathway of piroxicam is a water channel within the gel formulation. The pH of the
      gel did not affect the permeation rate of piroxicam significantly. As the
      concentration of piroxicam in the gel formulation increased, the permeation rate
      of piroxicam increased up to 1% and reached a plateau above 1%. Among various
      enhancers tested, polyoxyethylene-2-oleyl ether showed the highest enhancing
      effect, with an enhancement ratio of 2.84. Based on experimental results, the
      permeation rate of piroxicam can be controlled by changing the poloxamer
      concentration or drug concentration and by the addition of an appropriate
      enhancer.

PMID- 10071820
TI  - Effects of the host cavity size and the preparation method on the physicochemical
      properties of ibuproxam-cyclodextrin systems.
AB  - The effect of cyclodextrin (Cd) complexation on ibuproxam (IBUX) dissolution
      properties was studied by evaluating both the influence of Cd cavity size and the
      preparation method used for obtaining solid inclusion complexes. Binary systems
      of IBUX with natural Cds, prepared using different techniques (kneading, sealed
      heating, spray-drying), were studied by differential scanning calorimetry (DSC),
      hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy,
      scanning electron microscopy (SEM), and their dissolution behavior was evaluated
      according to the dispersed amount method. The nature and the dissolution
      performance of the end product appeared to be related to both steric factors of
      host molecule and preparation method of the solid system. The alpha Cd cavity
      size was less suitable for accommodating the IBUX molecule, whereas spray-drying
      and sealed-heating methods led to a true inclusion complex of IBUX in the beta Cd
      and gamma Cd cavity. In contrast, the kneading method did not lead in any case to
      a real inclusion complex. Spray-dried systems with beta Cd and gamma Cd were the
      most effective in achieving the enhancement of the IBUX dissolution rate.

PMID- 10071821
TI  - Development and in vitro evaluation of buccoadhesive tablets using a new model
      substrate for bioadhesion measures: the eggshell membrane.
AB  - For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive
      tablets based on gelatin/hydroxypropylcellulose (HPC),
      gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium
      carboxymethylcellulose (NaCMC) at different ratios were prepared by direct
      compression of the mixed powders. Metronidazole and benzydamine were used as
      model drugs. The in vitro bioadhesive properties, evaluated by a commercial
      tensile tester, were significantly affected by the model substrate employed, that
      is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane).
      The use of the biological substrate seemed to supply more reliable data. All
      studied formulations showed an erosion-diffusion mechanism of release, anomalous
      or non-Fickian release, in agreement with the behavior of the swellable systems.

PMID- 10071822
TI  - Ibuprofen agglomerates preparation by phase separation.
AB  - The compression ability and dissolution rate of ibuprofen are poor. There are
      many processes to optimize these properties through adapted formulations.
      However, it would be more satisfactory to obtain directly during the
      crystallization step crystalline particles that can be directly compressed and
      quickly dissolved. This was the aim of this work. Ibuprofen spherical
      agglomerates were obtained using a very simple method based on the difference of
      solubility of ibuprofen in ethanol and in water. By cooling down an ibuprofen
      saturated solution in an ethanol/water 50/50 mixture from 60 degrees C to room
      temperature under stirring, a phase separation occurs. Ibuprofen crystallizes in
      separated water droplets. After separation by sieving and drying, spherical
      agglomerates were obtained. A study of the physical properties of ibuprofen
      agglomerates was carried out using electron scanning microscopy and X-ray powder
      diffraction. The compression ability was tested using an instrumented tablet
      machine, and the dissolution rate was measured using continuous flow cells. An
      improvement in compression and dissolution properties of the spherical
      agglomerates produced was observed. The process of crystallization in a separated
      dispersed phase could be envisaged each time a drug exhibits opposite
      solubilities in two miscible solvents.

PMID- 10071823
TI  - Physical characterization of polymer electrolytes as novel iontophoretic drug
      delivery devices.
AB  - Polymer electrolytes are solid-like materials formed by dispersing a salt at the
      molecular level in a high molecular weight polymer such as poly(ethylene oxide)
      (PEO). They have been extensively studied for use in electrochemical applications
      such as batteries and display devices. This paper considers a novel application
      of polymer electrolytes as the basis of iontophoretic drug delivery systems.
      Polymer electrolyte films were cast from solutions of PEO and various drug salts
      using either water or an acetonitrile/ethanol mixture as the solvent. These films
      were characterized by variable-temperature polarizing microscopy (VTPM),
      differential scanning calorimetry (DSC), and alternating current (AC) impedance
      analysis. The films were around 100-micron thick and mechanically strong; the
      optical and thermal methods provided evidence that the polymer electrolytes had
      crystalline and amorphous phases, although some drugs may exist in films as
      nanodispersions. The amorphous phase is important as ions have greater mobility
      in this phase and therefore allow a current to be passed when the material is
      incorporated into a device such as one suitable for drug delivery by
      iontophoresis. The AC impedance analysis showed that the conductivity of the
      films varied between 10(-6) and 10(-3) S cm-1, depending on the salt, casting
      solvent, and temperature. Two drugs in particular were shown to be promising
      candidates in these systems: lidocaine hydrochloride and lithium chloride.

PMID- 10071824
TI  - Gonadorelin-induced testosterone release: a biological assay for quality
      assurance of gonadorelin in veterinary medicine.
AB  - Two experiments were conducted with bulls administered norgestomet and
      gonadorelin to determine if the gonadorelin-induced release of testosterone could
      be developed into a biological assay for quality assurance of gonadorelin.
      Implants containing norgestomet (0 to 36 mg) reduced the episodic release (r = 
      .81; P < .05) and mean concentrations of testosterone (r = -.82; P < .05).
      Gonadoreline-induced testosterone release increased (r = .99; P < .05) with
      increasing dosage of gonadorelin (up to 5 micrograms) in norgestomet-implanted
      bulls (36 mg). Maximal testosterone was released (> sixfold increase) with 5 to
      40 micrograms of gonadorelin. In summary, the gonadorelin-induced testosterone
      release in bulls administered a synthetic progestin is a sensitive (0.008
      microgram per kg body weight for 5 micrograms of gonadorelin) biological assay
      with a rapid turnaround time for the confirmation of gonadorelin potency. Based
      on a per-kg-body-weight basis, the norgestomet-treated bull is the most sensitive
      biological assay model.

PMID- 10071825
TI  - Antibacterial action of extracts of Clinopodium vulgare L. curative plant.
AB  - Clinopodium vulgare L. is one of the curative plants used in Bulgarian folk
      medicine, mainly during wars for the purposes of healing wounds. The
      antibacterial activity was studied based on its phytochemical properties. By
      colony forming unit (CFU)/ml values obtained in different intervals after
      inoculation of 5% extracts of Clinopodium vulgare L. in ethanol and propylene
      glycol, it has been proved that the plant showed a very strong action on
      bacteria. The effects of this action are on gram-positive and gram-negative
      microorganisms and also on isolated microorganisms at laboratory conditions from
      significant urocultures with multiple resistance. These results are very
      important as a basis for searching possibilities for utilizing the antibacterial
      properties of this plant pharmaceutically.

PMID- 10071826
TI  - Matrix tablets of carrageenans. I. A compaction study.
AB  - Carrageenans can be used as excipients for controlled-release tablets. The aim of
      this study was to determine their compaction and consolidation behavior to prove
      their usefulness for tableting. The Carr indices of the three carrangeenans, two
      kappa-carrageenans(Gelcarin GP-812 NF and GP-911 NF) and one tau-carrageenan
      (Gelcarin GP-379 NF), indicate that the materials are free flowing. They are
      polymers in the rubbery state. Their glass transition-temperature is about 0
      degree C analyzed by differential scanning calorimetry (DSC). The powders were
      analyzed regarding their compression behavior using an eccentric tableting
      machine. From data obtained during one compaction cycle, porosity-pressure and
      pressure-time plots were made. Compaction behavior is evaluated by fitting the
      pressure-time function to the pressure-time plot and by fitting the Heckel
      function to the porosity-pressure plot. The polymers show "viscoelastic"
      tableting behavior. Several additional tableting parameters were analyzed for
      strengthening the results obtained, namely, maximum work, maximum power, and the
      time between maximum upper punch force and maximum displacement of the upper
      punch. The crushing strength of the tablets is high; therefore, the carrageenans
      are able to form strong compacts. However, they remain in the rubbery state, as
      shown by thermomechanical analysis. In addition, elastic recovery is regarded at
      several times after ejection. Finally, after 10 days, it is about 30% as
      determined from the minimum of tablet height during the compression cycle. These
      results indicate that the carrageenans are suitable tableting excipients for
      controlled-release tablets. They show good compactibility and good consolidation
      behavior. Strong compacts with a high elastic recovery are formed; this means
      that the materials are able to embed drugs softly. Only a little stress and
      strain remains in the tablet. All three carrageenans show similar tableting
      behavior, and a flexible dosage form design is possible.

PMID- 10071827
TI  - Matrix tablets of carrageenans. II. Release behavior and effect of added cations.
AB  - Carrageenans are hydrocolloids in the rubbery state at standard conditions. They
      are useful excipients for controlled-release tablets. Three carrageenans, two
      kappa-carrageenans (Gelcarin GP-812 NF and GP-911 NF) and one iota-carrageenan
      (Gelcarin GP-379 NF), are analyzed regarding their release behavior in
      combination with sorption, swelling, and rheology. The iota-carrageenan has a
      higher substitution by sulfate groups. The kappa-carrageenan Gelcarin GP-812 NF
      contains a small amount of potassium chloride left over from processing. Water
      sorption of the pure materials was studied gravimetrically, and the rheology of
      different solutions (2% and 5% w/w) was studied by cup-cylinder rotation
      viscosimetry. Swelling was determined as the vertical expansion of the tablets
      with a specially designed swelling apparatus. Drug release from the tablets was
      performed by the USP paddle method for 8 hr. The data indicate that drug release
      increases when water sorption and swelling extent decrease and as viscosity
      increases. The order of release is nearly zero-order kinetics for theophylline
      monohydrate, a nonionic drug. Diffusion of the anionic drug diclofenac sodium is
      anomalous. In addition, the influence of the added salts potassium and calcium
      chloride on swelling and release was studied. Before tableting, physical mixtures
      of these salts with and without theophylline monohydrate were prepared. Swelling
      and release change in the same order, but this is only valid when the ionic
      interactions responsible for this are strong enough. Besides this, physical
      mixing of salts with the carrageenans can result in an increased release of drug
      caused by decreased cohesion of the matrix during drug release, mainly for
      calcium chloride.

PMID- 10071828
TI  - Particle size distributions in mesh cuts and microscopically estimated volumetric
      shape factors.
AB  - When particle size distribution parameters are calculated from sieve analysis, it
      is generally assumed that the distribution within the particle cut is either
      linear, producing a mean particle size equal to the average of the mesh openings
      (1-3), or that a more proper number is the geometric mean of these two apertures.
      It is shown here that particles within a mesh cut are not linearly distributed,
      but rather may be normally, long-normally, or biphasic combinations of the two.
      Three compounds were examined in this fashion, and results are reported here.

PMID- 10071829
TI  - Comparative bioavailability study of a generic naltrexone tablet preparation.
AB  - The bioavailability of a generic preparation of naltrexone (Narpan) was compared
      with the innovator product, Trexan. Twelve healthy volunteers participated in the
      study, conducted according to a completely randomized, two-way crossover design.
      The preparations were compared using the parameters area under the plasma
      concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time
      to reach peak plasma concentration Tmax. No statistically significant difference
      was observed between the logarithmic transformed AUC0-infinity and the
      logarithmically transformed Cmax values of the two preparations. Also, no
      statistically significant difference was observed between the untransformed Tmax
      values. In addition, the 90% confidence interval for the ratio of the logarithmic
      transformed AUC0-infinity values of Narpan over those of Trexan was found to lie
      between 0.87 and 1.01, while that of the logarithmic transformed Cmax values was
      between 0.94 and 1.23, both being within the bioequivalence limit of 0.80-1.25.
      The numerical values of the elimination half-life (t1/2) obtained with the two
      preparations were also not significantly different and were comparable to those
      reported in the literature.

PMID- 10071830
TI  - Comparative bioavailability study of two atenolol tablet preparations.
AB  - A study was conducted to compare the bioavailability of a generic product of
      atenolol (Normaten FC) with the innovator product, Tenormin. Twelve healthy adult
      volunteers participated in the study conducted according to a randomized, two-way
      crossover design. The preparations were compared using area under the plasma
      concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time
      to reach peak plasma concentration Tmax. No statistically significant difference
      was obtained between the Tmax values and the logarithmic transformed AUC0
      infinity and Cmax values of the two products. Moreover, the 90% confidence
      interval for the ratio of the logarithmically transformed AUC0-infinity values of
      Normaten FC over those of Tenormin was found to lie between 0.82 and 0.98, while
      that of the logarithmically transformed Cmax values was between 0.82 and 1.09,
      both being within the bioequivalence limit of 0.80-1.25. The values of
      elimination half-life t1/2 between the two products were also found comparable
      and not significantly different statistically. The t1/2 values obtained in our
      study were slightly longer than those reported in the literature for other
      population groups.

PMID- 10071831
TI  - Degradation products of mycophenolate mofetil in aqueous solution.
AB  - The thermal and peroxide-catalyzed degradation products of mycophenolate mofetil
      (1) were studied in aqueous solution at pH 2.0, 3.5, 6.0, and 8.2. The major
      thermal degradation product observed was mycophenolic acid (2). At pH 6.0 and
      8.2, 2 was the only product observed in the absence of peroxide, while at pH 2.0
      and 3.5, the lactone analogue of mycophenolic acid (5), a hydroxylactone due to
      oxygenation of the double bond (6), and an unidentified product were formed.
      Compound 6 degraded to 4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro
      isobenzofuran-5-car baldehyde (9) on prolonged storage and was present in the
      sample stressed at pH 2. Mycophenolic acid (2), the N-oxide of mycophenolate
      mofetil (3), the hydroxylactone of mycophenolic acid (6), and the erythro form of
      4-methoxy-5-methyl- 2-(2-methyl-5-oxo-tetrahydro-furan-2-yl)-3,6-dihydro-2H-1, 7
      dioxa-as-indacen-8-one (8) were observed in the presence of hydrogen peroxide at
      pH 3.5, 6.0, and 8.2. In addition, at pH 8.2, 4-hydroxy-4-(4-methoxy-5-methyl-8
      oxo-2,3,6, 8-tetrahydro-1,7-dioxa-as-indacen-2-yl)-pentanoic acid (7) was seen.
      Peroxide-stressed samples at pH 2.0 gave no major degradation peaks, but a small
      amount of the hydroxylactone of mycophenolic acid (6) was formed.

PMID- 10071832
TI  - Evaluation of the emulsifying properties of some cationic starches.
AB  - Different cationic potato, maize, and waxy maize starches were evaluated for
      their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic
      oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a
      concentration ranging from 1% to 5% (w/w) were prepared and characterized by
      droplet size and viscosity measurements, and the stability was evaluated visually
      and by electrical conductance measurements. None of the cationic potato, waxy
      maize starches, and maize starches with a low degree of substitution (DS) showed
      adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C
      [symbol: see text] bond 05914, 2% and 5% w/w; C [symbol: see text] bond 05907, 5%
      w/w) and pregelatinized (C [symbol: see text] bond 12504, 5% w/w) cationic maize
      starches with high-DS were visually stable. The initial mean droplet volume
      diameter of the emulsions prepared with these cationic starches in a 5% (w/w)
      concentration was similar and ranged from 2.40 to 2.84 microns; however, there
      was an important difference in droplet size distribution. The droplet size
      distribution of the emulsions prepared using the non-pregelatinized high-DS
      cationic starches was markedly narrower than in the case of the emulsions
      prepared using the pregelatinized high-DS cationic starches. The droplet size of
      the emulsions remained almost constant during 120 days of storage. Visual
      inspection and electrical conductance measurements showed that these emulsions
      were stable for at least 120 days.

PMID- 10071833
TI  - Effects of surfactant on release characteristics of clonidine hydrochloride from
      ethylcellulose film.
AB  - The effects of Tween 80 (polysorbate 80) and Span 80 (sorbitan monooleate)
      surfactants on release characteristics of clonidine hydrochloride from
      ethylcellulose 10 and 20 cps matrix films containing castor oil as a plasticizer
      were investigated. The release rates of drug from these films in water at 37
      degrees C were found to increase with the addition of surfactant, which was
      highest for the film prepared from ethylcellulose 20 cps with Tween 80. The
      experimental values of the cumulative amount of drug released were found to
      conform to the solution matrix model. The calculated values of the cumulative
      amount of clonidine hydrochloride released using the experimentally determined
      diffusion coefficients were also found to be in good agreement with the observed
      values.

PMID- 10071834
TI  - Simultaneous high-performance liquid chromatographic analysis for famotidine,
      ranitidine HCl, cimetidine, and nizatidine in commercial products.
AB  - A high-performance liquid chromatographic (HPLC) procedure for the simultaneous
      determination of famotidine (FMT), ranitidine HCl (RNT), cimetidine (CMT), and
      nizatidine (NZT) was developed using a two-level, full-factorial design with
      three variables (volume of methanol, percentage of triethylamine, and
      concentration of phosphate buffer) to select an acceptable mobile phase. A column
      (15 cm x 4.6 mm ID) of Inertsil ODS-2 (5 microns) was used, and 0.04 M aqueous
      sodium dihydrogen phosphate/acetonitrile/methanol/TEA at a proportion of
      345/20/35/0.7 (v/v/v/v) was the selected mobile phase (1 ml/min). The detection
      wavelength was set at 230 nm, and procaine HCl was used as the internal standard.
      Precision and linearity of the method were assessed. None of the commercial
      samples was found to be outside the compendial limits of 90.0% to 110.0% of the
      claim amount.

PMID- 10071835
TI  - The effect of 2-hydroxypropyl-beta-cyclodextrin on in vitro drug release of
      steroids from suppository bases.
AB  - The effects of 2-hydroxypropyl-beta-cyclodextrin (HPCD) on drug solubility and
      drug release from suppository bases were studied for dexamethasone (DX),
      dexamethasone acetate (DXA), hydrocortisone (HC), hydrocortisone acetate (HCA),
      and prednisolone acetate (PNA). It was found that HPCD significantly increased
      the aqueous solubility of all five steroids, and the increased drug solubility
      significantly influenced the drug release from the polyethylene glycol (PEG) base
      but not from the cocoa butter base.

PMID- 10071836
TI  - Studies of erythromycin maltobionate, a new derivative of erythromycin.
AB  - Erythromycin maltobionate, a new water-soluble derivative of erythromycin, was
      prepared, and its physiochemical and biological properties were evaluated. The
      derivative has considerable solubility in organic solvents. Its partition
      coefficient data in different organic solvent-water systems indicate it is
      possibly well distributed in various tissues in vivo. Antimicrobial potency in
      vitro of the derivative is 589 micrograms/mg, and its antimicrobial spectrum is
      comparable to that of the parent antibiotic. The LD50 value of the new derivative
      in mice intraperitoneally is 244.7 mg/kg. Results of this and the previous
      investigation of pharmacokinetics and protein binding indicate that the new
      derivative erythromycin maltobionate has a potential for possible clinical
      application.

PMID- 10071837
TI  - Vaginal wall mass.

PMID- 10071838
TI  - Atherosis revisited: current concepts on the pathophysiology of implantation site
      disorders.
AB  - There are two distinct histological manifestations of impaired placental
      implantation in humans--incomplete trophoblastic vascular invasion and atherosis.
      Both have been described to occur in pregnancies affected by a variety of
      disorders such as preeclampsia, fetal growth restriction, systemic lupus
      erythematosus, and diabetes. Our purpose was to integrate recent developments in
      the understanding of implantation site disorders into a pathophysiological
      scenario that interrelates these placentation disorders and associated pregnancy
      complications. Sources were identified from a MEDLINE search of English-language
      articles published from 1966 to 1997. Additional sources were identified from
      references cited in relevant reports. We selected articles relating to the
      following topics: atherosis, implantation site disorders, trophoblastic invasion,
      preeclampsia, fetal growth restriction, implantation site development,
      atherosclerosis, and endothelial activation-damage. A contemporary version of
      normal placentation, including vascular adaptation, was reviewed with comments on
      normal trophoblastic differentiation and vascular invasion. Specific
      abnormalities of the implantation site, including atherosis and incomplete
      trophoblastic invasion, were discussed in the context of placental site
      hypoperfusion and the association with pregnancy complications. It was concluded
      that atherosis and incomplete trophoblastic invasion may be both a consequence
      and a cause of placental site hypoperfusion resulting in the development of
      preeclampsia and a variety of other pregnancy disorders.

PMID- 10071839
TI  - Preeclampsia-associated hepatic hemorrhage and rupture: mode of management
      related to maternal and perinatal outcome.
AB  - This article is a critical review of the obstetric literature concerning
      preeclampsia-associated hepatic hemorrhage to develop guidelines conducive to
      optimal maternal and perinatal outcomes. An English literature search was
      performed for reports of hepatic hemorrhage or hepatic rupture in pregnancy
      during 1960 to 1997. Data were analyzed by Statmost packages using ANOVA, Chi
      square, and Fisher's exact tests. One hundred forty-one patients with hepatic
      rupture/hemorrhage were reported. The three most common presenting findings were
      epigastric pain, hypertension, and shock. With rare exception, patients had
      evidence of preeclampsia. Diagnosis was elusive and most frequently accomplished
      at laparotomy. When utilized, ultrasound and computed tomography (CT) were
      helpful diagnostic modalities. Maternal survival was highest in the arterial
      embolization treatment group. Maternal and perinatal survival improved
      considerably during the study interval. Route of delivery did not seem to impact
      survival rates. It was concluded that the application of ultrasound and CT for
      diagnosis and the use of hepatic artery embolization for treatment of hepatic
      hemorrhage/rupture seem to be beneficial management options for this rare event.

PMID- 10071840
TI  - Genetic factors in preterm delivery.
AB  - Tens of thousands of children deliver before they are full term each year.
      Although many social, environmental, and medical risk factors have been
      suggested, the etiology of a large percentage of preterm labor cases is still
      unknown. It has been noted for many years that preterm delivery is a condition
      that runs in families. Evidence concerning its aggregation among families, the
      recurrent nature of preterm labor, and its differing prevalence between races has
      led to the suggestion of a genetic cause for preterm delivery. There have been
      few formal studies to investigate this hypothesis. We suggest that modern
      molecular biology approaches can reveal the part that genes play in preterm
      delivery.

PMID- 10071841
TI  - Recent trends in teen births in the United States.
AB  - Teenage births and birth rates have dropped steadily during the 1990s. Overall,
      the teen birth rate declined 15 percent between 1991 and 1997. The trend in the
      1990s reverses a period of steep increases from 1986 to 1991. Despite the recent
      declines, the teen birth rate in 1997 is still higher than rates in the mid 1980s
      when they were at an all-time low (50-51 per 1,000). In general, teen birth rates
      have declined more for younger teenagers (15-17 years) than for older teens (18
      19 years). Among all race and ethnic groups, black teenagers have experienced the
      greatest declines in childbearing during the 1990s. From 1991 to 1997, the rate
      for black teens 15-19 years dropped 23 percent to the lowest level on record. A
      particularly noteworthy finding is that the birth rate for second births to all
      teenagers who have had a first birth (repeat childbearing) declined by 21 percent
      between 1991 and 1996. Despite the recent decline in teen births and birth rates,
      a growing number and proportion are to unmarried teens. Most teenagers giving
      birth in the 1990s are not married--78 percent overall in 1997. Teenage
      childbearing has important social and health consequences for the teenage mother
      herself and for her baby. Most teen births are unintended, the educational
      attainment of teen mothers is limited, teen mothers are less likely to receive
      timely prenatal care, and teens are more likely to smoke during pregnancy than
      are older women. As a consequence of these and other factors, babies born to teen
      mothers are at greater risk of preterm delivery and low birthweight. Teen
      pregnancy prevention has become a major focus of attention over the past several
      years, contributing to a wide variety of initiatives and strategies at the
      national, state and community level.

PMID- 10071842
TI  - International mortality rates and life expectancy: selected countries.
AB  - The total U.S. mortality rate for men and women, all causes combined, continues
      to decrease, but remains less favorable than that in many other developed
      countries. The 1995 age-adjusted rate for men was ranked 9th among 15 selected
      industrialized countries and that for women 11th. In 1996 the U.S. age-adjusted
      rate dropped to a record low of 491.6 per 100,000 population. Since 1990 this
      rate decreased substantially more among U.S. nonwhites than whites. The rates
      dropped 11 and 6 percent for nonwhite men and women, respectively, and 8 and 2
      percent for their white counterparts. Thus, the gender gap continues to narrow as
      do the racial differentials in U.S. life expectancy and mortality. International
      mortality data for 1995 indicate that Iceland had the best recorded age-adjusted
      rate for men (487.4 per 100,000 population)--just ahead of Japan which has had
      the lowest mortality rate for more than 20 years. Age-adjusted death rates among
      U.S. nonwhite men and for men in Scotland were ranked the lowest, while among
      women, the worst mortality rates were evident among the Danish and Scottish
      women. Although life expectancy values are improving in all 15 countries, U.S.
      longevity continues to fare poorly in comparison to other developed countries.
      The U.S. life expectancy for men was ranked 13th for the 1990-1995 period and
      11th for women. Longevity was the highest for men in Japan and Iceland, 76.4 and
      76.3 years, respectively, and the lowest for men in Finland (72.0 years). For
      women, longevity was the best in Japan at 82.4 years, and the worst in Denmark
      (77.8 years). Life expectancies for men during 1995-2000 are projected to improve
      from 1.6 years in New Zealand to 0.4 years in Japan. For women, life expectancy
      will remain at 80.8 years in Sweden while increasing 0.8 years in the United
      States, Germany, the United Kingdom and New Zealand.

PMID- 10071843
TI  - Laparoscopic and open appendectomies--average charges, 1997.
AB  - During 1997 the average total charge for an open appendectomy (OA) was $9,670
      while that for a laparoscopic appendectomy (LA) was $11,290. The 20 study states
      (those with 50 or more OAs) accounted for 77 percent of the 2,979 OA procedures
      investigated. The total charges ranged from $12,800 in California to $6,540 in
      Oklahoma. The hospital charges were more than 30 percent higher than the U.S.
      norm in California and Florida and more than 30 percent below it in Oklahoma and
      Washington. New York and New Jersey reported the highest physicians' fees while
      the Michigan doctors' charges were 35 percent below the average. Length of stay
      for an open appendectomy averaged 2.92 days across the country and ranged from
      3.33 days in New York to 2.33 days in Colorado. The hospital plus physicians'
      charges for LAs ranged from $14,350 in California (27 percent above the norm) to
      $9,210 in Colorado (18 percent below). California and Florida reported the
      highest hospital charges whereas those in New York were the lowest. The
      physicians' fees ranged from $4,280 in New York to $1,830 in Colorado. The
      patients with LAs remained in the hospital, on average, 2.22 days. The length of
      stay ranged from almost three days in Ohio to 1.62 days in Colorado.

PMID- 10071844
TI  - Savings and wealth in the United States: trends and implications.
AB  - As the debate over the future of Social Security in the United States begins to
      gather momentum, data suggest that many individuals are not heeding advice to
      increase personal savings. By its traditional measure, personal saving virtually
      disappeared in 1998. While there is some controversy over the measure, the
      dramatic decline points to changes in spending habits in recent years. There is
      little doubt that the robust economy and sharp rise in equity prices have played
      a major role in boosting consumption and the willingness of consumers to take on
      more debt. However, with individuals living longer, the data point to
      difficulties for many households in sustaining long retirements. This has
      implications for public policy, and the concept of forced saving should be part
      of any debate.

PMID- 10071845
TI  - Cubane tetrameric complexes of copper(I) chloride and bromide with triphenyl
      phosphite.
AB  - The crystal structures of tetra-mu 3-chloro-tetrakis[(triphenyl phosphite
      P)copper(I)], [Cu4Cl4(C18H15O3P)4], and tetra-mu 3-bromo-tetrakis [(triphenyl
      phosphite-P)-copper(I)], [Cu4Br4(C18H15O3P)4], are described. Both have distorted
      'cubane' Cu4X4 cores. Distortion of the cubane structure is reflected in X-Cu-X
      angles > 90 degrees and Cu-X-Cu angles < 90 degrees, and is more pronounced in
      the bromide complex.

PMID- 10071846
TI  - Hydrogen bonding in 4,4',6,6'-tetramethyl-biphenyl-2,2'-dicarboxylic acid.
AB  - The title compound, C18H18O4, crystallizes in the centrosymmetric space group
      P2(1)/c, with two molecules in the asymmetric unit. Each of the four independent
      carboxylic H atoms is ordered, and each participates in hydrogen bonding. The
      OD...OA distances in the hydrogen bonds are 2.598 (3), 2.608 (3), 2.652 (3) and
      2.641 (3) A. Two cyclic hydrogen-bonded dimers are found, neither occurring about
      a center of symmetry; each, however, occurs about a pseudo-center. Numerous
      hydrogen-bonded chains, all propagating along [010], are also present. The
      biphenyl twist angles are 88.4 (2) and 87.5 (2) degrees. Structural comparisons
      are made with the structures of the 'parent' compound, diphenic acid, and its
      4,4'- and 6,6'-dimethyl derivatives.

PMID- 10071847
TI  - Hydrogen bonding in 4-aminohippuric acid.
AB  - The title acid, C9H10N2O3, crystallized in the non-centrosymmetric space group
      P2(1)2(1)2(1) with one molecule in the asymmetric unit. Four hydrogen bonds occur
      whose donor-acceptor distances are: O1...O3 2.630 (2), N1...O3 3.090 (2), N2...O1
      3.099 (2), and N2...O2 3.022 (2) A, and whose angles fall in the range 163 (2)
      173 (2) degrees. The H atoms in these bonds are ordered. Cyclic hydrogen-bonded
      dimers are not formed; through second-level graphs, only hydrogen-bonded chains
      occur. These form a strongly three-dimensional array of hydrogen bonds. The
      dihedral angle between the core plane and the carboxyl plane is 54.8 (2) degrees,
      and between the core plane and the plane of the amino group, 34 (1) degree. The
      structure is compared with a previous determination by Chakrabarti & Dattagupta
      [Z. Kristallogr. (1993), 207, 53-58] and with the structure of the parent
      molecule, hippuric acid.

PMID- 10071848
TI  - Hydrogen bonding in (2R,3R)-(+)-2,3-dimethoxybutanedioic acid [(+)-tartaric acid
      dimethyl ether].
AB  - The title acid, C6H10O6, crystallized in the non-centrosymmetric space group I2,
      with half a molecule in the asymmetric unit (the molecular symmetry is 2). In the
      single type of hydrogen bond, the carboxylic H atom is ordered, and the OD...OA
      distance is 2.665 (2) A. Each molecule is linked to four others by hydrogen bonds
      and to two others by C-H...O interactions. The dihedral angle between
      intramolecular carboxyl-group planes is 85.2 (1) degree.

PMID- 10071849
TI  - Inhibitory effects of constituents from Cynomorium songaricum and related
      triterpene derivatives on HIV-1 protease.
AB  - From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR.
      (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as
      inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50%
      inhibitory concentrations (IC50) of 8 and 6 microM, respectively. Amongst various
      synthesized dicarboxylic acid hemiesters of related triterpenes, inhibitory
      activity tended to increase in the order of oxalyl, malonyl, succinyl and
      glutaryl hemiesters, for triterpenes such as ursolic acid, oleanolic acid and
      betulinic acid. The most potent inhibition was observed for the glutaryl
      hemiesters, with an IC50 of 4 microM. From the water extract of the stems of C.
      songaricum, flavan-3-ol polymers, consisting of epicatechin as their extender
      flavan units, were also found to be potent inhibitory principles against HIV-1
      protease.

PMID- 10071850
TI  - Synthesis and biological evaluation of 5-arylfuro[2,3-d]pyrimidines as novel
      dihydrofolate reductase inhibitors.
AB  - A series of about fifty novel 5-arylfuro[2,3-d]pyrimidine derivatives were
      synthesized as potential inhibitors of dihydrofolate reductase (DHFR) arising
      from different species. Weak enzyme inhibition was observed for most of the
      compounds, with only a few reaching IC50 values less than 30 microM. With regards
      to antibacterial and anti-malarial potency, only seven compounds showed a modest
      in vitro activity against some bacteria strains and only three products proved
      significantly active against P. falciparum.

PMID- 10071851
TI  - 2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. III.) Synthesis of
      metabolites and metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and
      YM264 as platelet-activating factor (PAF) receptor antagonists.
AB  - The metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 was
      investigated, and their metabolites were compared with separately synthesized
      materials by measuring 1H-NMR spectra, mass spectra, and HPLC retention times,
      and evaluated for platelet activating factor (PAF) antagonistic activity. YM461
      was metabolized by two different metabolic pathways (cleavage of the thiazolidine
      ring and oxidation of the benzyl position), whereas YM264 was metabolized by
      three metabolic pathways. The minor metabolite M7 from YM264 possessed potent PAF
      antagonistic activity, as strong as YM264 and this existed as an active
      metabolite. From pharmacokinetics studies, YM264 was almost completely absorbed
      from the gastrointestinal tract, but readily metabolized in rats. In dogs,
      pharmacokinetic parameters of YM264 were significantly improved compared to those
      in rats, and YM264 tended to show better pharmacokinetics than YM461 due to an
      extension of the half-life period.

PMID- 10071852
TI  - Synthesis of trimethylhydroquinone derivatives as anti-allergic agents with anti
      oxidative actions.
AB  - A novel series of trimethylhydroquinone derivatives was synthesized and evaluated
      for their anti-lipid peroxidation activity in rat liver microsomes, inhibition of
      rat basophilic leukemia-1 (RBL-1) cell 5-lipoxygenase and 48 h homologous passive
      cutaneous anaphylaxis (PCA) activity in rats. 4-[4-[4-(Diphenylmethyl)-1
      piperazinyl]-butoxy]-2,3,6-trimethyl phenol (9c) exhibited the ability to inhibit
      Fe(3+)-ADP induced NADPH dependent lipid peroxidation (IC50 = 5.3 x 10(-7) M), 5
      lipoxygenase ((IC50 = 3.5 x 10(-7) M) and PCA reaction (57% inhibition at 100
      mg/kg p.o.).

PMID- 10071853
TI  - Synthesis of new N-containing maltooligosaccharides, alpha-amylase inhibitors,
      and their biological activities.
AB  - Fifteen new N-containing maltooligosaccharides were obtained using the
      chemoenzymatic method. Among these compounds, maltooligosaccharides having 6
      amino-6-deoxy-D-sorbitol residue, (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H
      azepine residue, and (3R,5R)-3,4,5-trihydroxypiperidine residue at the reducing
      end showed strong inhibitory activities for human pancreatic alpha-amylase (HPA)
      (EC 3.2.1.1) and human salivary alpha-amylase (HSA). The administration of
      (3R,4R,5R,6S)-hexahydro-3,5,6-trihydroxy-1H-azepine-4-yl O-alpha-D-glucopyranosyl
      (1-->4)-alpha-D-glucopyranoside (13, IC50 = 4.3 x 10(-5) M for HPA, IC50 = 8.2 x
      10(-5) M for HSA) and (3R,5R)-3,5-dihydroxypiperidine-4-yl O-alpha-D
      glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (18, IC50 = 3.4 x 10(-5) M for
      HPA, IC50 = 4.6 x 10(-5) M for HSA) to ICR mice suppressed postprandial
      hyperglycemia.

PMID- 10071854
TI  - Identification of inhibitors of an 80 kDa protease from Trypanosoma cruzi through
      the screening of a combinatorial peptide library.
AB  - Two orthogonal peptide combinatorial libraries were screened to discover
      inhibitors of Tc80 protease, a novel target from Trypanosoma cruzi involved in
      host cell invasion. These libraries were composed of 15,625 structurally
      diversified tripeptides, partitioned in 125 mixtures. The screening led to a low
      micromolar inhibitor which was actually an HF cleavage by-product H-Ipe-D-Tic-D
      Glu(S-paratolyl)-OH. IC50 values of several analogous molecules of this hit were
      determined and are discussed. For the best compounds, conformational analysis
      revealed a high degree of similarity in shape with a potent prolylendopeptidase
      inhibitor, SUAM-1221.

PMID- 10071855
TI  - Optimum spray congealing conditions for masking the bitter taste of
      clarithromycin in wax matrix.
AB  - The effects of operating conditions in the spray-congealing process on the
      release and the micromeritic properties of clarithromycin (CAM) wax matrix were
      evaluated. CAM wax matrix with 30% CAM, 60% glyceryl monostearate (GM) and 10%
      aminoalkyl methacrylate copolymer E (AMCE) was manufactured at various atomizer
      wheel speeds and liquid feed rates with a spray dryer. Release of CAM from the
      matrix exhibited a two-phase pattern, probably due to the dissolution of the fine
      portions broken on the surface of the matrix. The slope and the extrapolated y
      intercept of the subsequent release pattern were defined as the release rate and
      the initial amount of release of CAM from the matrix, respectively. These release
      parameters, as well as the volume median diameter and the specific surface area
      of matrix, were selected as response variables, and multiple regression analysis
      was performed. For specific surface area and initial amount of release, a minimum
      point was observed on the contour curve when the atomizer wheel speed was
      constant and the liquid feed rate was varied. For the release rate, a maximum
      point was observed on the contour curve under the same conditions. These points
      were considered preferable for masking the bitter taste of CAM preparation.
      Microscopic observation revealed that a small spherical matrix with a smooth
      surface could be obtained with a high atomizer wheel speed and optimum liquid
      feed rate. This matrix also possessed excellent properties for taste masking,
      with small initial amount of release and subsequent high rate of release. In
      conclusion, the congealing speed of melt droplets was the dominant factor in
      masking the bitter taste of CAM.

PMID- 10071856
TI  - Synthesis of 2-phenylbenzofuran derivatives as testosterone 5 alpha-reductase
      inhibitor.
AB  - A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or
      alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and
      evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities
      in vitro. Against rat enzyme, the carbamoyl derivatives had more potent
      inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6
      carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives.
      Against human enzyme, the 6-substituted derivatives had more potent inhibitory
      activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino
      derivatives tended to show stronger inhibitory activities against human type 1
      enzyme than against type 2 enzyme, but they were not largely selective.

PMID- 10071857
TI  - Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent
      antihypertensive agents with antiplatelet aggregation activity.
AB  - A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized
      and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists,
      with the aim of finding a novel antihypertensive agent potently exhibiting both
      activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at
      the 1-position exhibited both activities, and varied significantly in terms of
      the substituents at the 4-position of the pyrroloazepine ring. Among the
      compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]
      4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a,
      SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/
      0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea
      pig arteries. This compound exhibited antihypertensive activity and a duration of
      action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in
      conscious spontaneously hypertensive rats, as well as potent antiplatelet
      aggregation activity.

PMID- 10071858
TI  - Effects of catechins on superoxide and hydroxyl radical.
AB  - Superoxide (O2-.) was reduced by the addition of superoxide dismutase (SOD: O2-.
      scavenger) and catechins. In competitive reactions utilizing different
      concentrations of spin-trap agent, the IC50 values of each sample were changed.
      With regard to the Cu2+/H2O2 and Fe2+/H2O2 reaction systems, metal chelater,
      hydroxyl radical (.OH) scavenger and catechins eliminated the levels of .OH. For
      the Cu2+/H2O2 reaction systems, the IC50 for .OH scavenger changed, but that for
      metal chelater and catechins did not. However, for the Fe2+/H2O2 reaction system,
      the IC50 for .OH scavenger and catechins changed, whereas that for metal chelater
      did not. The ESR signal for free Cu2+ was changed by addition of metal chelater
      and catechins. In the spectrophotometer experiments, it was confirmed that the
      CuCl2 spectrum was changed by addition of metal chelater and catechins but not by
      .OH scavenger. Conversely, the FeSO4 spectrum was not changed by addition of .OH
      scavenger or catechins, but was altered by metal chelater. Lipid peroxidation was
      inhibited by catechins in a concentration-dependent manner. Therefore, it was
      suggested that the catechins did not scavenge directly the generated .OH from the
      Cu2+/H2O2 reaction system, but inhibited the generation of .OH by acting on the
      Cu2+/H2O2 reaction system. On the other hand, with respect to the .OH generated
      from the Fe2+/H2O2 reaction system, it was suggested that the catechins had a
      direct scavenging capacity of the .OH, but had little chelating activity of iron.
      It was confirmed that catechins have the ability to scavenge for O2-. as well as
      .OH and to inhibit the generation of .OH by chelation with metal ions.

PMID- 10071859
TI  - Hepatoprotective and hepatotoxic actions of oleanolic acid-type triterpenoidal
      glucuronides on rat primary hepatocyte cultures.
AB  - The protective effects of oleanolic acid-type saponins and their derivatives on
      in vitro immunological liver injury of primary cultured rat hepatocytes were
      studied. A known antihepatotoxic saponin (chikusetsusaponin IVa, 1) showed
      hepatoprotective activity in this model. Although a rhamnosyl derivative (2) of 1
      similarly showed hepatoprotective activity, its prosapogenin (5) did not show any
      hepatoprotective activity. On the contrary, 5 exhibited cytotoxicity toward liver
      cells. In the absence of antiserum, monodesmosyl saponins showed hepatotoxicity,
      while the bisdesmosyl saponins except for 1, did not show such hepatotoxicity. In
      order to clarify the effects of the sugar residues at C-3 and C-28 responsible
      for hepatoprotective and hepatotoxic actions, oleanolic acid 3-O-glucuronide (2a)
      and oleanolic acid 28-O-glucoside (2b) were prepared and tested. 2b showed
      neither hepatoprotective action nor hepatotoxicity. In contrast, 2a was effective
      at 90 microM on hepatoprotection, although it showed strong hepatotoxicity.
      Oleanolic acid (2c) itself showed both hepatoprotective action and weak
      hepatotoxicity. Therefore, the hepatoprotective activity of these types of
      saponins could represent a balance between hepatoprotective action and
      hepatotoxicity.

PMID- 10071860
TI  - Interconversion between 3D molecular representations: some macromolecular
      applications of spherical harmonic-Bessel expansions about an arbitrary center.
AB  - An accurate interconversion of three-dimensional molecular spatial information
      between two alternative orthogonal representations is demonstrated. These
      alternative descriptions are useful for exhaustive six-dimensional grid searches
      of empirical energy functions and for estimating the contents of asymmetric units
      in sparsely packed, non-centrosymmetric crystalline arrays. To illustrate the
      fidelity of this interconversion, it is implemented to perform an exhaustive grid
      search in six-dimensional relative rotational and translational space (phase
      space) with the spherical harmonic-Bessel representation. This search is an
      extension of Crowther's crystallographic fast rotational overlap function from
      Patterson space to direct, three-dimensional space. The search uses a three
      dimensional spherical harmonic expansion about a single center to represent a
      probe molecule's shape, charge and van der Waals parameters and numerous complete
      expansions about single centers to represent the complementary shape,
      electrostatic potential and van der Waals potential of several target sites about
      the complementary molecule. The rapid calculation of unique, complete expansions
      about numerous sites on a grid is made possible by application of the Fourier
      convolution theorem. Expansions from nearby grid points can be used to
      reconstruct the same molecular shape accurately, if this shape is contained
      entirely within the spherical zone of expansion about each grid point. This
      arbitrariness for the choice of origin, and the accuracy of interconversion
      between three-dimensional spherical harmonic-Bessel and Fourier representations,
      suggest a method for describing the contents of non-centrosymmetric, sparsely
      packed crystals. Incomplete Fourier representations (diffraction amplitudes)
      provide complex spherical harmonic-Bessel coefficients for a crystal packed with
      symmetry-enforced, non-centrosymmetrically arranged, non-overlapping spherical
      expansion zones.

PMID- 10071861
TI  - Occurrence of selected bacterial groups in the faeces of piglets fed with
      Bacillus coagulans as probiotic.
AB  - A microbiological analysis of piglet faeces was performed on samples collected
      from animals fed a diet without any additive, animals fed a diet that contained
      Bacillus coagulans CNCMI-1061 as probiotic, and animals fed a diet that contained
      Zn-bacitracin. The analysis was carried out in concurrence with a zootechnical
      trial. Selected bacterial groups (lactic acid bacteria, lacotococci, enterococci,
      aerobic and anaerobic cocci, total and faecal coliforms, clostridia, bacteroides,
      bifidobacteria) were determined at day 1 and after 1, 4 and 10 weeks of life.
      Numbers of enterococci, coliforms (especially faecal coliforms) showed a decrease
      over time with probiotic, more evident than with the antibiotic. Daily
      administration of B. coagulans allowed this bacterium to become integrated into
      the enteric microflora where it is transient. These results seem to show a
      positive effect of B. coagulans addition on cocci and faecal coliforms. We
      suggest that this probiotic may represent an alternative to antibiotics.

PMID- 10071862
TI  - Production of lipase by soil fungi and partial characterization of lipase from a
      selected strain (Penicillium wortmanii).
AB  - Filamentous fungi from soil were screened for their ability to produce lipase.
      Among 56 filamentous fungi tested, one strain identified as Penicillium wortmanii
      was selected as the highest lipase producer. Maximum lipase production (12.5
      U/ml) was obtained in 7-days cultures utilizing 5% (w/v) olive oil as the carbon
      source. Optimum pH and temperature for crude lipase were 7.0 and 45 degrees C,
      respectively. The enzyme was stable at 40 and 45 degrees C and it retained about
      55% of its activity when heated at 50 degrees C for 1 hour.

PMID- 10071863
TI  - Effect of urokinase on the extracellular virulence properties of Pseudomonas
      aeruginosa and Burkholderia cepacia.
AB  - The influence of urokinase and oxygen availability on growth, siderophore,
      protease and lipase production in Burkholderia cepacia and non-mucoid (PA01) and
      mucoid (PaWH) strains of Pseudomonas aeruginosa was assessed for cells grown in
      batch culture under iron-restriction. Siderophore production decreased with
      increasing concentration of urokinase in B. cepacia independent of oxygen
      availability but decreased in both strains of P. aeruginosa only under oxygen
      depleted conditions. Protease activity was enhanced for all three strains
      irrespective of oxygen content whereas lipase production increased in B. cepacia
      and decreased in PA01 under both sets of growth conditions and varied with oxygen
      availability in PaWH. The evidence presented suggests that urokinase could
      contribute to the pathophysiology of pulmonary infections.

PMID- 10071864
TI  - Cloning and expression in Escherichia coli of an azoreductase gene from
      Clostridium perfringens and comparison with azoreductase genes from other
      bacteria.
AB  - A genomic library of Clostridium perfringens ATCC 3626 was constructed in phage
      lambda gt11 and screened with an antibody against the C. perfringens
      azoreductase, which catalyzes the reduction of azo dyes to aromatic amines. A
      positive recombinant phage, containing a 3.8 kb DNA fragment insert was selected
      and purified. Lytic and lysogenic Escherichia coli cultures infected with the
      recombinant phage had higher azoreductase activity than cultures infected only
      with the vector lambda gt11. The 3.8 kb DNA fragment was amplified by PCR and
      found to hybridize with one band from C. perfringens DNA digested with EcoR1,
      indicating the presence of a single copy of the azoreductase gene. The fragment
      also hybridized with DNA from other azoreductase-producing Clostridium species, a
      Eubacterium sp., Enterobacter cloacae, Citrobacter amalonaticus and E. coli, but
      not with DNA from some other species of anaerobic bacteria capable of reducing
      azo dyes. The data indicate that the sequence of the azoreducatse gene of C.
      perfringens is conserved in some anaerobes and facultative anaerobes, but not in
      others, and that different types of azoreductase genes must be found in other
      anaerobic bacteria.

PMID- 10071865
TI  - Transformation of a flocculating Saccharomyces cerevisiae using lithium acetate
      and pYAC4.
AB  - A flocculating yeast Saccharomyces cerevisiae ura3 was transformed by the method
      based on treatment of intact cells with lithium acetate plus single-stranded
      carrier DNA using the shuttle vector pYAC4. The transformation efficiency was
      above 10(3) transformants per microgram of plasmid DNA which is similar to other
      described yeast transformation systems. Under selective pressure, the transformed
      cells were stable and maintained the flocculation ability. Thus, this simple
      transformation system can be used for gene expression studies in flocculating
      yeasts, overcoming disadvantages of conventional methods such as the spheroplast
      one.

PMID- 10071866
TI  - A polylinker-derived sequence, PL, highly increased translation efficiency in
      Escherichia coli.
AB  - Pokeweed (Phytolacca americana) antiviral protein (PAP) is a highly specific
      ribosome-inactivating glycosidase. The PAP gene was isolated and cloned in an
      expression vector containing a polylinker-derived sequence (PL) but devoid of a
      Shine-Dalgarno (SD) sequence. Surprisingly, E. coli cells transformed with this
      vector produced over twice the amount of PAP than that with the consensus SD
      sequence. Computer analysis of the 5' terminal region of PAP mRNA revealed a
      nucleotide sequence (ACCUACUCGAGUUAG) which was complementary to two domains in
      16S rRNA. The heptanucleotide ACCUACU (box I) is complementary to nucleotides
      1434-1440 and the GAGUUAG (box II) to nucleotides 507-513 in 16S rRNA of E. coli.
      To examine the role of this sequence in the translation of PAP mRNA, single or
      both boxes were mutated and the protein yield was measured. Mutation of box I and
      of box II resulted in a 2.7 and 5.3 fold decrease in protein yield respectively,
      indicating that the PAP gene expression was dependent on the presence of both
      boxes. To investigate whether PL also increases expression of other genes, human
      calcitonin monomeric and tetrameric genes were used as reporters. It was found
      that the expression level was doubled compared to that by SD. These results
      demonstrate that the PL is an efficient translational initiator and may be used
      for high level expression of certain genes in E. coli. The possible mechanisms
      for the high level expression are discussed.

PMID- 10071867
TI  - Comparison of the immunogold labeling of single light chains and whole
      immunoglobulins with anti-kappa on LR-white and epoxy sections.
AB  - The purpose of this study was to examine the intensity of the immunogold labeling
      of kappa light chains as single molecules and as parts of whole immunoglobulin
      molecules in LR-White sections and epoxy sections both practically and
      theoretically. Human renal tissues including deposits of kappa light chains and
      immune complex deposits of IgA were embedded in both LR-White resin and epoxy
      resin. Immunogold labeling was performed on unetched thin sections of both resins
      with anti-kappa or anti-IgA. In all relevant cases the immunolabeling was intense
      on the LR-White sections. Single kappa light chains were intensely labeled also
      on the epoxy sections, although not as intensely as on LR-White sections. In
      contrast, the immunogold labeling of whole immunoglobulins with anti-kapp and
      anti-IgA was weak and hardly positive on the epoxy sections. Consequently, the
      quotient labelinglr-white/labelingepoxy for anti-kappa was significantly lower
      for labeling of single light chains (3.6) than for labeling of whole
      immunoglobulins (15.9). The corresponding quotient for labeling of whole
      immunoglobulins with anti-IgA was 17.0. Supported by theoretical considerations,
      it is believed that the copolymerization between the epoxy resin and the antigens
      allows the knife to cleave the large whole immunoglobulins more easily than the
      smaller single kappa chains. This prevents satisfactory immunolabeling of whole
      immunoglobulins on epoxy sections whether anti-kappa or anti-IgA is used as
      antibodies, while single kappa chains are easily immunolabeled.

PMID- 10071868
TI  - Image processing and analysis of fluorescent labelled cytoskeleton.
AB  - Cytoskeleton elements play an important role in cellular processes including
      normal and pathological conditions or even cell death. Although
      immunofluorescence microscopy techniques have proved useful to study the
      cytoskeleton, description and comparative results commonly rely on the direct
      visual analysis of the targeted cells. We report here an objective and
      quantitative method to analyze the cytoskeletal pattern of cultured HeLa cells
      based on image processing and analysis (IPA) of fluorescent labelled cytoskeleton
      components. Different structural quantifiable characteristics using IPA
      facilities (densitometric profile, number of branched points, Euler number,
      convexity, orientation value) allow accurate characterization and differentiation
      of the three types of fibre nets studied (microtubules, actin microfilament, and
      cytokeratin intermediate filaments). The application of the analytical methods
      presented here provides information concerning the organization and modification
      of cytoskeleton components, and could aid in the further understanding of
      structural and functional aspects of the cytoskeleton under normal and
      pathological conditions.

PMID- 10071869
TI  - Vitellogenin is glycosylated in the fat body of the stick insect Carausius
      morosus and not further modified upon transfer to the ovarian follicle.
AB  - Synthesis and secretion of vitellogenin (Vg) polypeptides were studied in egg
      laying females of the stick insect Carausius morosus following in vivo exposure
      to [35S]-methionine and acetyl-N-[3H]-glucosamine. The specificity of
      radioisotope incorporation was assessed by in vitro inhibition with tunicamycin
      and carbohydrate extraction with endo-glycosidase H. Vg polypeptides change in
      molecular weight during synthesis in the fat body and are not further modified
      upon transfer to the haemolymph or to the oocyte, suggesting that they are
      already fully glycosylated prior to secretion. Radioactivity in the fat body was
      initially distributed over cisternae of the rough endoplasmic reticulum and
      gradually transferred to the Golgi apparatus. Within an hour of exposure,
      electron-dense granules budding from the trans-Golgi network became
      preferentially labeled. Radioactivity in the ovarian follicle was restricted to
      the yolk granules of the cortical ooplasm and to the amorphous material lying
      within the intercellular channels of the follicular epithelium. This amorphous
      material was also shown to react positively when tested with a monoclonal
      antibody raised specifically against a Vg polypeptide.

PMID- 10071870
TI  - Review of photon interaction cross section data in the medical and biological
      context.
AB  - The probability of a photon (x-ray, gamma-ray, bremsstrahlung, etc) of a given
      energy E undergoing absorption or scattering when traversing a layer of material
      Z can be expressed quantitatively in terms of a linear attenuation coefficient mu
      (cm(-1)). Since mu is dependent on the material's density, rho (g cm(-3)), which
      can be variable, the quantity usually tabulated is the mass attenuation
      coefficient mu/rho (cm2 g(-1)) in which the dependence on the density has been
      removed. Mu/rho, in turn, can be obtained as the sum of the different types of
      possible interactions of photons with atoms of the material. For photon energies
      below 1 MeV the major interaction processes to be considered are incoherent
      (Compton) scattering, coherent (Rayleigh) scattering and atomic photoeffect
      absorption. Above 1 MeV one must also include nuclear-field pair production and
      atomic-field (triplet) production, and above 5 MeV one in principle should
      include photonuclear absorption, although the latter is neglected in data
      tabulations up to the present time. This review includes a selective history of
      measurements and theory relating to mu/rho from the turn of the century up to the
      present time, and is intended to provide a basis for further calculations and
      critical tabulations of photon cross section data, particularly as required by
      users in radiation medicine and biology. The mass energy-absorption coefficient
      mu(en)/rho is also briefly discussed.

PMID- 10071871
TI  - Monte Carlo simulation of light fluence in tissue in a cylindrical diffusing
      fibre geometry.
AB  - The propagation of light emitted by a linear light diffuser in a cylindrical
      hollow organ was investigated by means of the Monte Carlo (MC) method. The height
      and radius of the cavity, scattering (mu(s)) (or reduced scattering, mu'(s)) and
      absorption (mu(a)) coefficients, anisotropy (g), and refractive indices of the
      media involved (n1, n2) are required as input data by the MC code, as are
      characteristics of the light diffuser (length, delivered power and emission
      profile). Results of our MC model were tested by measuring the light fluence rate
      in a tissue-simulating phantom (mu(a) = 0.5 cm(-1), mu(s) = 23 cm(-1) and g =
      0.75) irradiated at 633 nm with a cylindrical diffuser. Since geometric and
      optical parameters determine the behaviour of light propagation in tissue, MC
      simulations with different sets of input parameters were carried out to provide
      qualitative as well as quantitative data useful in planning photodynamic therapy.
      Data are reported on light penetration and fluence rate build-up at mu(a) and
      mu'(s) values ranging between 0.1 and 5 cm(-1) and 2.5 and 50 cm(-1),
      respectively. Furthermore, results suggest that a shift and spread could occur in
      the isofluence curves along the symmetry axis, which depend on the diameter of
      the treated lumen as well as on the emission profile of the light diffuser. Using
      our data it is possible to estimate how inaccuracy in knowledge of the optical
      coefficients can affect (i.e. usually by increasing) the light dose scheduled at
      a certain depth into tissue.

PMID- 10071872
TI  - Monte Carlo calculations of the dose backscatter factor for monoenergetic
      electrons.
AB  - Recently, there has been growing interest in beta emitters for therapeutic uses,
      especially in connection with so-called endovascular (or intravascular)
      brachytherapy. Since accurate dose estimation is necessary for the success of
      such applications, some problems in beta-ray dosimetry need further study. Among
      these problems, we have investigated the effect of electron backscattering on
      dose, which has significance not only for accurate dose estimation but also for
      new source design. In this study, an empirical measure of electron
      backscattering, known as the dose backscatter factor, was calculated using EGS4
      Monte Carlo calculations for monoenergetic electrons and various scattering
      materials. Electron energies were 0.1, 0.5, 1.0, 2.0 and 3.0 MeV in combination
      with Al (Z = 13), Ti (Z = 22), Sr (Z = 38), Ag (Z = 47) and Pt (Z = 78)
      scatterers. The dose backscatter factor ranged from 10% to 60%, depending on
      electron energy and material, and was found to increase with the atomic number Z
      by a log(Z + 1) relationship. A method is presented for calculating the beta-ray
      dose backscatter factors using the results of this study. To demonstrate the
      efficacy of this method, a dose backscatter factor depth profile for 32P near a
      water/aluminium interface was calculated and these calculated results were found
      to generally reproduce the depth profile obtained from direct EGS4 calculations
      using the 32P spectrum. The data presented in this study can be used to calculate
      dose backscatter factors for any combination of beta emitter/scatterer whose
      atomic number ranges from 13 to 78.

PMID- 10071873
TI  - Dose calculation models for proton treatment planning using a dynamic beam
      delivery system: an attempt to include density heterogeneity effects in the
      analytical dose calculation.
AB  - The gantry for proton radiotherapy at the Paul Scherrer Institute (PSI) is
      designed specifically for the spot-scanning technique. Use of this technique to
      its full potential requires dose calculation algorithms which are capable of
      precisely simulating each scanned beam individually. Different specialized
      analytical dose calculations have been developed, which attempt to model the
      effects of density heterogeneities in the patient's body on the dose. Their
      accuracy has been evaluated by a comparison with Monte Carlo calculated dose
      distributions in the case of a simple geometrical density interface parallel to
      the beam and typical anatomical situations. A specialized ray casting model which
      takes range dilution effects (broadening of the spectrum of proton ranges) into
      account has been found to produce results of good accuracy. This algorithm can
      easily be implemented in the iterative optimization procedure used for the
      calculation of the optimal contribution of each individual scanned pencil beam.
      In most cases an elemental pencil beam dose calculation has been found to be most
      accurate. Due to the long computing time, this model is currently used only after
      the optimization procedure as an alternative method of calculating the dose.

PMID- 10071874
TI  - Electron contamination and build-up doses in conformal radiotherapy fields.
AB  - The dose in the build-up region depends upon the primary photon beam,
      backscattered radiation from the patient and contamination radiation from outside
      the patient. In this paper, a model based on measured data is proposed which
      allows the build-up dose for arbitrarily shaped treatment fields to be
      determined. The dose in the build-up region is assumed to comprise a primary
      photon component and a contamination component that is a function of the field
      size and shape. This contamination component, for modelling purposes, is
      subdivided into contributions that correspond to elements of 1 cm by 1 cm cross
      sectional area at the plane of the isocentre. The magnitude of these components
      has been obtained by fitting measured data to an exponential function. The
      exponent was found to vary linearly with depth for energies between 4 MV and 20
      MV. The coefficient decreased linearly with depth at 4, 6 and 8 MV, but exhibited
      a broad build-up region at 20 MV. The primary component, in the build-up region,
      could be approximated by a 100 - (100 - PSD) e(-mu d) function, where PSD is the
      primary surface dose. The values obtained during the fitting procedure were used
      to calculate dose in the build-up region for arbitrarily shaped fields. Good
      agreement was found in each case.

PMID- 10071875
TI  - Modelling the thermal impact of a discrete vessel tree.
AB  - Based on a modelling technique to calculate the thermal influence of a single
      vessel segment, a combination of segments representing a vessel tree is
      presented. At segment junctions the blood temperature is passed with a correction
      for a single vessel artefact. Blood leaving the modelled arterial vessel network
      at a junction or at the end of a terminal branch need not be equilibrated with
      the local surrounding tissue temperature. The thermal effect of this
      equilibration process can be taken into account using the 'sink set'. Blood
      entering a venous vessel tree is given an inflow temperature based on the tissue
      temperatures in the 'sample set'. With these sets we model the thermal impact of
      the vasculature too small to be taken into account discretely. The formation of
      the sink/sample sets is subject of current research; to show the capabilities of
      the presented method we present a minimal simulation collection with cube-shaped
      sets in combination with limited vasculature. The results of using the entire
      simulation volume as sink and sample sets for all the terminal branches matches
      the reference temperature profile best.

PMID- 10071876
TI  - Determination of the object surface function by structured light: application to
      the study of spinal deformities.
AB  - The projection of structured light is a technique frequently used to determine
      the surface shape of an object. In this paper, a new procedure is described that
      efficiently resolves the correspondence between the knots of the projected grid
      and those obtained on the object when the projection is made. The method is based
      on the use of three images of the projected grid. In two of them the grid is
      projected over a flat surface placed, respectively, before and behind the object;
      both images are used for calibration. In the third image the grid is projected
      over the object. It is not reliant on accurate determination of the camera and
      projector pair relative to the grid and object. Once the method is calibrated, we
      can obtain the surface function by just analysing the projected grid on the
      object. The procedure is especially suitable for the study of objects without
      discontinuities or large depth gradients. It can be employed for determining, in
      a non-invasive way, the patient's back surface function. Symmetry differences
      permit a quantitative diagnosis of spinal deformities such as scoliosis.

PMID- 10071877
TI  - SOFIA: spatially optimal fast initial analysis of biomagnetic signals.
AB  - A method of analysing biomagnetic signals is presented which focuses attention on
      activity in a specific region of interest. The method is based on the
      construction of virtual sensors, corresponding to linear combinations of lead
      fields that are optimally localized within the region of interest. This method is
      fast and stable. It is tested against physiologically plausible computer
      generated signals and also against more elaborate analysis of real data. The
      results show that the method can be very effective as a fast scanning tool
      identifying activity from pre-defined regions of interest.

PMID- 10071878
TI  - Magnetocardiographic analysis of the two-dimensional distribution of intra-QRS
      fractionated activation.
AB  - The spatial distribution of high-frequency components in magnetic signals during
      the QRS complex of the human heartbeat was investigated. Cardiomagnetic signals
      were recorded simultaneously using 49 first-order magnetogradiometer channels of
      a multi-SQUID system with a low noise power density. The QRS fragmentation score
      S, as a measure of the fragmentation of the bandpass-filtered QRS complex, was
      examined for its sensitivity and specificity to discriminate 34 healthy
      volunteers, 42 post-myocardial infarction patients and 43 patients with coronary
      heart disease and with a history of malignant sustained ventricular tachycardia
      or ventricular fibrillation. The multichannel information was visualized by two
      dimensional mapping of the score values of the single channels. By averaging the
      score values for the seven central channels, S7, the score values of all 49
      channels, S49, and calculating the standard deviation for all 49 channels, D49, a
      higher sensitivity and specificity for detecting patients with ventricular
      tachycardia (VT) or ventricular fibrillation (VF) was reached than by analysis of
      a single channel. Combination of these parameters furnishes a sensitivity of 90%
      and a specificity of 70% for identifying patients prone to VT/VF. The results
      were compared with diagnostic information obtained from the QRS duration of the
      signal as well as with results obtained by modified QRS integral mapping.

PMID- 10071879
TI  - Errors of the backextrapolation method in determination of the blood volume.
AB  - Backextrapolation is an empirical method to calculate the central volume of
      distribution (for example the blood volume). It is based on the compartment
      model, which says that after an injection the substance is distributed
      instantaneously in the central volume with no time delay. The occurrence of
      recirculation is not taken into account. The change of concentration with time of
      indocyanine green (ICG) was observed in an in vitro model, in which the volume
      was recirculating in 60 s and the clearance of the ICG could be varied. It was
      found that the higher the elimination of ICG, the higher was the error of the
      backextrapolation method. The theoretical consideration of Schroder et al
      (Biomed. Tech. 42 (1997) 7-11) was proved. If the injected substance is
      eliminated somewhere in the body (i.e. not by radioactive decay), the
      backextrapolation method produces large errors.

PMID- 10071880
TI  - Mass-energy absorption coefficient and backscatter factor ratios for kilovoltage
      x-ray beams.
AB  - For low-energy (up to 150 kV) x-rays, the ratio of mass-energy absorption
      coefficients for water to air, (mu(en)/rho)w.air, and the backscatter factor B
      are used in the conversion of air kerma, measured free-in-air, to water kerma on
      the surface of a water phantom. For clinical radiotherapy, similar conversion
      factors are needed for the determination of the absorbed dose to biological
      tissues on (or near) the surface of a human body. We have computed the mu(en)/rho
      ratios and B factor ratios for different biological tissues including muscle,
      soft tissue, lung, skin and bone relative to water. The mu(en)/rho ratios were
      obtained by integrating the respective mass-energy absorption coefficients over
      the in-air primary photon spectra. We have also calculated the mu(en)/rho ratios
      at different depths in a water phantom in order to convert the measured in
      phantom water kerma to the absorbed dose to various biological tissues. The
      EGS4/DOSIMETER Monte Carlo code system has been used for the simulation of the
      energy fluence at different depths in a water phantom irradiated by a kilovoltage
      x-ray beam of variable beam quality (HVL: 0.1 mm Al-5 mm Cu), field size and
      source-surface distance (SSD). The same code was also used in the calculation of
      the B factor ratios, soft tissue to water and bone to water. The results show
      that the B factor for bone differs from the B factor for water by up to 20% for a
      100 kV beam (HVL: 2.65 mm Al) with a 100 cm2 field. On the other hand, the
      difference in the B factor between water and soft tissue is insignificant (well
      within 1% generally). This means that the B factors for water may be directly
      used to convert the 'in-air' water kerma to surface kerma for human soft tissues.

PMID- 10071881
TI  - Treatment planning for brachytherapy: an integer programming model, two
      computational approaches and experiments with permanent prostate implant
      planning.
AB  - An integer linear programming model is proposed as a framework for optimizing
      seed placement and dose distribution in brachytherapy treatment planning. The
      basic model involves using 0/1 indicator variables to describe the placement or
      non-placement of seeds in a prespecified three-dimensional grid of potential
      locations. The dose delivered to each point in a discretized representation of
      the diseased organ and neighbouring healthy tissue can then be modelled as a
      linear combination of the indicator variables. A system of linear constraints is
      imposed to attempt to keep the dose level at each point to within specified
      target bounds. Since it is physically impossible to satisfy all constraints
      simultaneously, each constraint uses a variable to either record when the target
      dose level is achieved, or to record the deviation from the desired level. These
      additional variables are embedded into an objective function to be optimized.
      Variations on this model are discussed and two computational approaches--a branch
      and-bound algorithm and a genetic algorithm--for finding 'optimal' seed
      placements are described. Results of computational experiments on a collection of
      prostate cancer cases are reported. The results indicate that both optimization
      algorithms are capable of producing good solutions within 5 to 15 min, and that
      small variations in model parameters can have a measurable effect on the dose
      distribution of the resulting plans.

PMID- 10071882
TI  - Secondary electron fluence perturbation by high-Z interfaces in clinical proton
      beams: a Monte Carlo study.
AB  - Fluence perturbation of secondary electrons from clinical proton beams (50-250
      MeV) by thin high-Z planar interfaces was studied with Monte Carlo simulations.
      Starting from monoenergetic proton pencil beams, proton depth doses and proton
      fluence spectra were calculated, both in homogeneous water and near thin high-Z
      interfaces by using the proton transport Monte Carlo code PTRAN. This code was
      modified extensively to enable modelling of proton transport in non-homogeneous
      geometries. From the proton fluence spectra in water and in the interface
      materials, electron generation spectra were calculated analytically and were then
      used as input for an electron transport calculation with the Monte Carlo code
      EGS4/PRESTAII to obtain electron doses and electron fluence spectra. The
      interface materials used in the study were graphite, Al, Ti, Cu, Sn and Au. We
      found significant electron fluence perturbations on both sides of the planar
      interfaces, resulting in an electron dose increase upstream and a decrease
      downstream from the interfaces, with the magnitude of the effect depending
      strongly on the atomic number of the interface. For the most extreme case
      studied, 250 MeV protons and a gold interface, we obtained an electron dose
      increase of 41% upstream of the interface and a decrease of 15% downstream with
      both perturbations having a spatial extent of about 700 microm. The total dose
      perturbation due to this effect amounts to a 5% increase upstream and a 2%
      decrease downstream. A detailed analysis of dose and fluence perturbation is
      presented for a wide range of materials and proton energies.

PMID- 10071883
TI  - Intensity modulation methods for proton radiotherapy.
AB  - The characteristic Bragg peak of protons or heavy ions provides a good
      localization of dose in three dimensions. Through their ability to deliver
      laterally and distally shaped homogenous fields, protons have been shown to be a
      precise and practical method for delivering highly conformal radiotherapy.
      However, in an analogous manner to intensity modulation for photons, protons can
      be used to construct dose distributions through the application of many
      individually inhomogeneous fields, but with the localization of dose in the Bragg
      peak providing the possibility of modulating intensity within each field in two
      or three dimensions. We describe four different methods of intensity modulation
      for protons and describe how these have been implemented in an existing proton
      planning system. As a preliminary evaluation of the efficacy of these methods,
      each has been applied to an example case using a variety of field combinations.
      Dose-volume histogram analysis of the resulting dose distributions shows that
      when large numbers of fields are used, all techniques exhibit both good target
      homogeneity and sparing of neighbouring critical structures, with little
      difference between the four techniques being discerned. As the number of fields
      is decreased, however, only a full 3D modulation of individual Bragg peaks can
      preserve both target coverage and sparing of normal tissues. We conclude that the
      3D method provides the greatest flexibility for constructing conformal doses in
      challenging situations, but that when large numbers of beam ports are available,
      little advantage may be gained from the additional modulation of intensity in
      depth.

PMID- 10071884
TI  - A potential application to the study of microscopic energy deposition in a solid
      by means of heavy charged-particle induced photochromic alterations in a tissue
      equivalent matrix.
AB  - A theoretical study was carried out to investigate the feasibility of using the
      radiation-induced colour decay of photochromic molecules embedded in a polymer
      matrix as a probe for studying the microscopic energy deposition of heavy charged
      particles (HCPs) in a tissue-equivalent solid. The theoretical treatment makes
      use of the radial dose distribution function as derived from gas-phase physics,
      together with the effects of the increase in temperature and of matrix
      degradation on the colour-decay kinetics of the photochromic molecules, according
      to empirical models derived for the solid state. Bearing in mind the non
      stochastic nature of the model, the use of gas-phase physics at the level of
      radiation interaction, and the fact that some empirical quantities used have been
      established macroscopically, all factors which signify that extra caution is
      required in the interpretation of the results, it is shown that when the optimum
      information retrieval time (after track formation) is considered the technique
      may be able to resolve differences in the energy deposition pattern by different
      HCPs in the nanometre range (1-10 nm; material's mass density 1.2 g cm(-3)) from
      the track axis. Most importantly, though, the present study aims to erect a
      theoretical framework for the possible application of the technique and to
      highlight those aspects which are likely to be critical to its practical usage,
      such as particle type and energy range, and spatial scale and magnitude of the
      expected effect together with its dependence on time, the physical
      characteristics of the matrix, and the kinetic behaviour of the type of
      photochromic molecule studied. Furthermore, it establishes a rationale for
      interpreting the experimentally observed (if available) colour changes in the HCP
      track in terms of the microscopic distribution of energy deposition in it.

PMID- 10071885
TI  - Accounting for treatment delays when treating highly proliferative tumours.
AB  - This study was undertaken to investigate the possibility of increasing the dose
      per fraction or increasing the number of fractions to account for treatment
      delays occurring during radiotherapy treatments for highly proliferative tumours.
      The linear quadratic model with time was used to determine the difference in
      biological effective dose (BED) for the original schedule and the schedule
      including a treatment delay. Tables of extra fractions and extra dose per
      fraction required to account for a number of possible delays have been
      determined. It has been shown that for tumours with very short potential doubling
      times it is best to deliver the extra dose as an increase in dose per fraction
      rather than an increase in the number of fractions, while for tumours with
      moderately short potential doubling times (above 7 days) the reverse is true. The
      equivalent uninterrupted schedules, which would have delivered the same effects
      to the tumour, have also been determined.

PMID- 10071886
TI  - Optimal electron and combined electron and photon therapy in the phase space of
      complication-free cure.
AB  - The possibility of using intensity-modulated high-energy electrons beams alone or
      in combination with photon beams to treat tumours located at depths from 5 cm to
      25 cm has been investigated. A radiobiologically based optimization algorithm
      using the probability of complication-free tumour control has been used to
      calculate the optimal dose distributions. Two different target volumes have been
      used; one advanced cervical cancer with locally involved lymph nodes and one
      astrocytoma in the upper brain hemisphere. Treatments with only electron beams
      and also combinations between electron and photon beams have been investigated.
      The dependence of the expected treatment outcome on the beam energy and
      directions was investigated, and to some extent on the number of beam portals. It
      is shown that the beam direction intervals resulting in a high expected treatment
      outcome increase with increasing electron energy and also with some electron
      photon combinations. For an eccentrically placed, not too deeply situated tumour
      surrounded by sensitive normal tissue it is shown that the expected treatment
      outcome can be improved by using electron beams in combination with photon beams
      compared with using two photon beams, and using two electron beams results in
      almost as high an expected treatment outcome. The possibility of improving the
      dose conformity from electron beams by adding photon fields parallel or
      orthogonal to the electron beams is demonstrated.

PMID- 10071887
TI  - Application of a fuzzy pattern classifier to decision making in portal
      verification of radiotherapy.
AB  - With the large volume of electronic portal images acquired and stringent time
      constraints, it is no longer feasible to follow the convention whereby the
      radiation oncologist reviews and approves or rejects all portals. For that
      purpose we have developed a portal image classifier based on the fuzzy k-nearest
      neighbour (k-NN) algorithm. Each portal image is represented by a feature vector
      that consists of translational and rotational errors in the placement of
      radiation field borders that were measured in the portal image. Memberships in
      the acceptable portal class for the reference portal images within a training
      dataset were defined by a radiation oncologist expert. The fuzzy k-NN portal
      image classifier was trained and tested on a dataset of 328 portal images
      acquired during tangential irradiations of the breast. The memberships in the
      acceptable portal class produced by the fuzzy k-NN algorithm agreed very well
      with those defined by the expert. The linear correlation coefficient was equal to
      0.89. Performance of the fuzzy k-NN classifier was also evaluated from the portal
      decision-making point of view using the measures of accuracy, sensitivity and
      specificity. The fuzzy k-NN portal classifier was capable of identifying almost
      all the truly unacceptable portals with an acceptably low false alarm rate.

PMID- 10071888
TI  - A large-area ionization chamber for portal image calibration.
AB  - Methods of removing the effects of linear accelerator (linac) output fluctuation
      from electronic portal images are described and compared. The output of the linac
      is measured using a specially constructed large-area ionization chamber during
      imaging and recorded with the image. The use of a dose-rate signal directly from
      the linac monitor chamber is discussed. Various versions of a quadratic thickness
      calibration scheme are tested, incorporating linac output data measured by the
      ionization chamber. Experimental results are presented showing that the
      incorporation of data from the ionization chamber gives improved absolute
      calibration accuracy and flatness. Immediately after calibration, the mean
      systematic thickness error in calibration of a uniform 136.8 mm water-equivalent
      slab was shown to be no more than 0.6 mm with a thickness variation within each
      image also of no more than +/-0.8 mm. This was true even when imaging with an
      unstable linac beam giving mean thickness errors between images of 8.8 mm and
      variations within each image of +/-4.9 mm without the ionization chamber
      correction. Up to one month after calibration, use of the ionization chamber to
      remove short-term linac fluctuations is shown to still keep mean thickness errors
      to less than 1.6 mm with variations within each image of no more than +/-1.4 mm.

PMID- 10071889
TI  - Measurement of electrical current density distribution in a simple head phantom
      with magnetic resonance imaging.
AB  - Knowledge of the influence of the human skull on the electrical current (d.c.)
      distribution within the brain tissue could prove useful in measuring impedance
      changes inside the human head. These changes can be related to physiological
      functions. The studies presented in this paper examine the current density
      distribution in a simple phantom consisting of a saline filled tank (to simulate
      scalp and brain) and a ring made of dental grade plaster of Paris (to simulate
      the human skull). Images of the distribution of the d.c. density of the phantom
      with and without the plaster of Paris ring were produced using a magnetic
      resonance imaging technique. These images indicate that the skull is likely to
      produce a more uniform d.c. density within the brain.

PMID- 10071890
TI  - The preprocessing of retinal images for the detection of fluorescein leakage.
AB  - Images of the human retina are routinely used in clinical practice for the
      diagnosis and management of eye disease. Increased permeability of retinal blood
      vessels, which is a clinically significant feature, can be visualized with a
      process known as fluorescein angiography as leakage of fluorescence dye into the
      surrounding tissues. Analyses of such images can be quantified but significant
      degradation of images due to uneven illumination or occluded optical pathways is
      often incurred during image capture. We describe a procedure to restore
      fluorescein angiographic retinal images so that quantitative computation can be
      reliably performed. Analysis of the image acquisition system reveals that
      captured images are composed of two functions, one describing the true underlying
      image and the other the degradation incurred. These two functions are independent
      of one another and it is possible to estimate the degradation from an isolated
      captured image and restore it appropriately. Any leakage of fluorescein dye is
      then detected by analysing the restored angiographic sequence over time and
      finding areas of the image that do not have the usual decrease in fluorescence
      intensity.

PMID- 10071891
TI  - Development of tissue-simulating optical phantoms: poly-N-isopropylacrylamide
      solution entrapped inside a hydrogel.
AB  - The average turbid optical properties of the N-isopropylacrylamide (NIPA) polymer
      solution entrapped inside a polyacrylamide hydrogel (called an NIPA/PAAM gel
      system) were studied using a multiwavelength oblique-incidence reflectometer. The
      turbidity of such a system can be drastically changed by simply switching the
      temperature from below the low critical solution temperature of the NIPA, around
      33 degrees C, to above. The absorption coefficient and the reduced scattering
      coefficient were obtained as a function of wavelength for samples with selected
      NIPA and blue dextran concentrations. It is found that the scattering of the
      optical phantom comes from the NIPA polymer chains and the absorption from the
      blue dextran. The turbid optical properties of an NIPA/PAAM gel system can be
      tuned to simulate biological tissues at a specific wavelength by varying
      compositions of NIPA and blue dextran and further modified by controlling the
      temperature.

PMID- 10071892
TI  - Long-term reproducibility optimization of an x-ray process for bone architectural
      evaluation during osteoporosis.
AB  - Non-invasive and in vivo assessment of bone architectural changes at high
      resolution is of considerable interest in osteoporosis. In this note, the use of
      an x-ray acquisition system in the evaluation of the architectural quality of
      trabecular bone by radiographic texture analysis is optimized to achieve good
      long-term reproducibility. First, radiographic and digitization processes are
      modelled and defined. Procedures to make radiographs and their digital images are
      fixed. Then, measurements of the modulation transfer function (MTF) of the entire
      acquisition chain were completed. These measurements provide an MTF in excess of
      30% at a spatial frequency of 2.5 lp/mm. Also, results of a fractal texture
      analysis made on digital images of calcaneus radiographs show a mean coefficient
      of variation of 2.07%. These data show that good long-term reproducibility can
      make the x-ray acquisition system efficient for patient follow-up, or evaluation
      of treatment regimes for osteoporosis. Finally, it is shown that fractal texture
      parameters are statistically different in an osteoporotic population and in a
      control group. Therefore, this system should also be of medical interest.

PMID- 10071893
TI  - Needle sterility during strabismus surgery.

PMID- 10071894
TI  - Ophthalmologic outcome after third cranial nerve palsy or paresis in childhood.
AB  - PURPOSE: The purpose of this study was to evaluate the causes and ophthalmologic
      outcome of oculomotor nerve palsy or paresis in children younger than 8 years of
      age. METHODS: Patients evaluated between 1985 and 1997 were retrospectively
      reviewed. Data analyzed included vision, residual strabismus after surgery,
      aberrant reinnervation, binocular function, and anisometropia. Long-term outcome
      was assessed in patients followed-up longer than 6 months. RESULTS: Forty-one
      patients were identified. The most frequent causes were congenital (39%),
      traumatic (37%), and neoplastic (17%). Visual acuities were reduced in 71% of
      patients at the time of the initial visit. Long-term outcome could be assessed in
      20 of the 41 patients (49%), with a mean follow-up of 3.6 years (range, 0.5 to 13
      years). Visual acuities were reduced because of amblyopia in 35% and nonamblyopic
      factors in 25% of patients in the long-term outcome group at last follow-up. The
      best response to amblyopia therapy was in the congenital group, in which all
      patients improved to normal visual acuity. Strabismus surgery was performed on 8
      of 20 children (40%) followed-up, none of whom demonstrated measurable stereopsis
      after operation despite improved alignment. Aberrant reinnervation was present in
      9 of 20 patients (45%). Only 3 patients fully recovered from their oculomotor
      nerve injuries, and these were the only patients to regain measurable stereopsis.
      The causes in those 3 patients were congenital, traumatic, and neoplastic.
      CONCLUSIONS: Oculomotor nerve palsy/paresis is associated with poor visual and
      sensorimotor outcome in children younger than 8 years of age. The best
      ophthalmologic outcome was in the resolved cases (3 of 20; 15%). Amblyopia
      therapy was most effective with congenital causes, but treatment results were
      poor with other causes. Young children with posttraumatic and postneoplastic
      oculomotor nerve injuries demonstrated the worst ophthalmologic outcomes.

PMID- 10071895
TI  - Magnetic resonance imaging after surgical transposition defines the
      anteroposterior location of the rectus muscle pulleys.
AB  - INTRODUCTION: Connective tissue pulleys serve as the functional origins of the
      rectus extraocular muscles (EOMs) and constrain the sideslip of the posterior EOM
      bellies after transposition surgery. Anterior to the pulleys, EOM paths
      appreciably displace to reach their transposed insertions. The inflection points
      in the EOM paths from minimal posterior displacement to maximal anterior
      displacement should define the anteroposterior location of the EOM pulleys after
      transposition. METHODS: Contiguous cross-sectional magnetic resonance images were
      obtained in planes perpendicular to the long axis of the orbit over its entire
      anteroposterior extent before and after operation in 6 patients who underwent
      rectus muscle transposition surgery. Four patients underwent full tendon width
      transposition of the vertical rectus muscles laterally for lateral rectus palsy.
      Two of these patients had augmentation of the transposition with sutures that
      fixated the temporal margins of the transposed muscles posteriorly to the sclera
      adjacent to the borders of the lateral rectus muscle. One patient underwent full
      tendon width transposition of the horizontal rectus muscles superiorly for
      superior rectus palsy. One patient underwent full tendon width transposition of
      both lateral rectus muscles inferiorly for "A" pattern esotropia. Paths of EOMs
      were defined relative to the area centroid of the orbit. Pulley locations were
      inferred from EOM paths. The postoperative change in EOM pulley location was
      obtained by subtracting the preoperative pulley location from the postoperative
      pulley location for each image plane. RESULTS: For all patients, the
      postoperative change in EOM belly location was relatively small posterior to the
      globe-optic nerve junction. The 2 patients with abducens palsy who underwent
      placement of posterior augmentation sutures, however, demonstrated a
      significantly larger displacement of the posterior vertical rectus paths compared
      with similar patients who did not receive augmentation sutures. For all
      horizontally transposed vertical rectus muscles and inferiorly transposed lateral
      rectus muscles, the inflection of the EOM path began 3 mm anterior to the globe
      optic nerve junction. For the superiorly transposed medial rectus muscle and
      lateral rectus muscle, the inflection began 6 mm anterior to the globe-optic
      nerve junction. CONCLUSIONS: The anteroposterior locations of the EOM pulleys can
      be defined by analysis of EOM displacement after transposition surgery.
      Augmentation of transpositions by posterior suturing displaces the EOM pulleys
      substantially more than nonaugmented transpositions.

PMID- 10071896
TI  - The psychosocial effects of amblyopia study.
AB  - PURPOSE: The purpose of this study was to assess the psychosocial effects of
      growing up with and living with amblyopia and to determine whether patients with
      amblyopia but without strabismus encounter psychosocial problems similar to those
      encountered by individuals with strabismus. METHODS: A 20-question survey
      focusing on medical background, education, self-image, history of amblyopia,
      treatment of amblyopia, and effects of amblyopia on work, school, friendships,
      and self-esteem was provided to patients with amblyopia but not strabismus at
      Saint Louis University Eye Institute and at the University of Iowa Department of
      Ophthalmology. In addition, patients were evaluated in terms of somatization,
      obsession-compulsion, interpersonal sensitivity, depression, and anxiety. Results
      for patients with amblyopia were compared with those of strabismic, normative,
      and psychopathologic groups using the Hopkins Symptom Checklist (HSC). RESULTS:
      Twenty-five patients with amblyopia but without strabismus or previous surgery
      responded. A significant number of patients felt that amblyopia interfered with
      school (52%) and work (48%) to some degree and were generally affected in their
      lifestyle (50%). Fewer were affected in their play of sports (40%) or were
      influenced as to their job choice (36%). Patients with amblyopia as a whole had a
      greater degree of somatization, obsessive-compulsive behavior, interpersonal
      sensitivity, depression, and anxiety than patients with strabismus and HSC
      control subjects. Differences between patients with amblyopia and those with
      strabismus were not statistically significant (P > .05), but differences between
      patients with amblyopia and HSC control subjects were significant (P < .05) in
      each category. Patients with amblyopia, however, were less symptomatic in these
      areas than HSC Anxious and HSC Depressed groups. CONCLUSION: Psychosocial
      difficulties related to amblyopia affect individuals' self-image, work, school,
      and friendships. Amblyopia has a significant effect on psychosocial functioning
      and warrants aggressive screening, prevention and treatment during the
      amblyogenic years.

PMID- 10071897
TI  - Instrument-induced measurement errors during strabismus surgery.
AB  - PURPOSE: The purpose of this study was to determine the clinical setting where
      errors in measurements of muscle position during strabismus surgery made by the
      Scott curved ruler or by calipers become important and to characterize the
      magnitude of those errors. METHODS: Geometric analysis was used to determine the
      measurement error between true arc lengths of 3.0 to 20.0 mm versus Scott curved
      ruler measurements and caliper measurements for axial lengths ranging from 18 to
      30 mm. RESULTS: For measurements less than 9.0 mm, neither the Scott curved ruler
      nor calipers had any clinically important measurement error for any axial length.
      For axial lengths substantially smaller than 21 mm or larger than 24 mm, the
      Scott curved ruler, although more accurate than calipers, caused clinically
      important measurement errors with arc length measurements as small as 12 mm in
      very small eyes and 14 mm in large eyes. For axial lengths of 30 mm or more, both
      calipers and the Scott curved ruler had similar accuracy for measuring long arc
      lengths. CONCLUSIONS: Both the Scott curved ruler and calipers are accurate in
      measuring arc lengths 9.0 mm or less. For longer arc length measurements,
      accuracy becomes dependent on axial length. The Scott curved ruler, although
      substantially more accurate than calipers for most common axial lengths, can
      introduce clinically important measurement errors when measuring arc lengths as
      small as 12 mm. Axial length should be considered when measuring muscle position
      during strabismus surgery.

PMID- 10071898
TI  - Childhood blindness.
AB  - PURPOSE: The objective of this study was to summarize available data regarding
      pediatric blinding diseases worldwide and to present the most up-to-date
      information on childhood blindness in the United States. METHODS: We obtained
      data from a complete search of the world literature and from direct contact with
      each of the schools for the blind in the United States. RESULTS: Five percent of
      worldwide blindness involves children younger than 15 years of age; in developing
      countries 50% of the population is in this age group. By World Health
      Organization criteria, there are 1.5 million children worldwide who are blind:
      1.0 million in Asia, 0.3 million in Africa, 0.1 million in Latin America, and 0.1
      million in the rest of the world. There are marked differences in the causes of
      pediatric blindness in different regions, apparently based on socioeconomic
      factors. In developing countries, 30% to 72% of such blindness is avoidable, 9%
      to 58% is preventable, and 14% to 31% is treatable. The leading cause is corneal
      opacification caused by a combination of measles, xerophthalmia, and the use of
      traditional eye medicine. There is no national registry of the blind in the
      United States, and most of the schools for the blind do not keep data regarding
      the cause of blindness in their students. From those schools that do have this
      information, the top 3 causes are cortical visual impairment, retinopathy of
      prematurity, and optic nerve hypoplasia. There has been a significant increase in
      both cortical vision loss and retinopathy of prematurity in the past 10 years.
      CONCLUSIONS: There are marked regional differences in the prevalence and causes
      of pediatric blindness, apparently based on socioeconomic factors that limit
      prevention and treatment schemes. In the United States the 3 leading causes of
      pediatric blindness are cortical visual impairment, retinopathy of prematurity,
      and optic nerve hypoplasia. There is a need for more complete and more uniform
      data based on the established World Health Organization reporting format.

PMID- 10071899
TI  - The effectiveness of latanoprost for the treatment of pediatric glaucoma.
AB  - PURPOSE: Latanoprost is a prostaglandin F2alpha analogue that substantially
      reduces intraocular pressure (IOP) in adults with open-angle glaucoma or ocular
      hypertension. The efficacy and safety of latanoprost in children is unknown. We
      wished to evaluate latanoprost therapy for children with glaucoma. METHODS: This
      was a prospective study of all patients who were given latanoprost at our
      institution between September 1996 and January 1998. The baseline IOP was
      compared with the postlatanoprost IOP for each patient, and side effects and any
      iris color change were noted at each follow-up examination. Responders were
      defined as those who had at least a 15% IOP reduction on latanoprost, whereas
      nonresponders showed less than a 15% IOP reduction on latanoprost. RESULTS: Fifty
      seven eyes of 48 pediatric patients with a variety of glaucoma diagnoses and an
      average age of 7.1 years were included in the study. Of these, 31 eyes of 31
      patients had interpretable IOP data; the mean IOP reduction for this group after
      the addition of latanoprostwas 0.9% (0.2 mm Hg). Six patients (6 eyes) were
      responders, with an average IOP reduction of 8.5 mm Hg (34%), whereas the
      majority of patients (25) were nonresponders. In the responders, there was a good
      correlation (r = 0.9) between baseline IOP and the magnitude of IOP reduction.
      Responders were significantly more likely to have juvenile open-angle glaucoma
      and to be older than nonresponders. Systemic and ocular side effects were
      infrequent and mild, and no patient had noticeable iris color changes.
      CONCLUSIONS: When used in a group of pediatric patients with a variety of
      glaucoma diagnoses and on various therapies, latanoprost is effective in only a
      minority of cases. In selected patients, however, latanoprost shows an impressive
      ocular hypotensive effect, comparable with that obtained when this drug is used
      in adults with open-angle glaucoma. This drug appears to be well tolerated in
      this short-term study of pediatric patients with glaucoma.

PMID- 10071900
TI  - Glaucoma in Sturge-Weber syndrome.
AB  - BACKGROUND: In glaucoma associated with Sturge-Weber syndrome (SWS), medical
      treatment often fails to control intraocular pressure, thus requiring surgical
      intervention that may result in serious complications. METHODS: Eighteen
      consecutive patients with SWS were reviewed retrospectively at the King Khaled
      Eye Specialist Hospital. An intraocular pressure less than 20 mm Hg, plus stable
      optic nerve cup-to-disc ratio and corneal diameter (or visual fields where
      appropriate), were parameters chosen to indicate that the glaucoma was being
      controlled. RESULTS: Glaucoma was found in 15 of 18 patients (22 eyes). The mean
      follow-up time was 62 months (range, 12 to 148 months). Medical treatment alone
      was successful in 5 patients (7 eyes); the remainder required surgical
      intervention. The initial surgical procedures included cyclocryotherapy, YAG
      laser goniotomy, surgical goniotomy, and trabeculotomy or trabeculectomy. Eight
      eyes required subsequent surgery, 5 with Molteno or Ahmed implants. Early
      postoperative choroidal effusion and hemorrhage occurred in 4 eyes and resolved
      spontaneously. Hemorrhagic choroidal detachment with total retinal detachment
      developed in 2 patients 3 to 5 months after surgery. In 1 patient a recurrent
      serous choroidal detachment after suture lysis was associated with total optic
      atrophy. CONCLUSIONS: Glaucoma in SWS is common. Control of glaucoma was
      successfully achieved with medical treatment in 7 of 22 eyes of our 15 SWS
      glaucoma patients, and we consider it the initial treatment of choice. Of the 15
      eyes that required surgery, late postoperative complications resulted in loss of
      vision as a result of persistent postoperative hypotony in 3 eyes that underwent
      surgical procedures.

PMID- 10071901
TI  - The decreasing incidence and severity of retinopathy of prematurity.
AB  - PURPOSE: We sought to determine whether the incidence of retinopathy of
      prematurity (ROP) at our institution has changed since the Cryo-ROP recruitment
      period 10 years ago. METHODS: We determined the incidences of threshold ROP,
      prethreshold ROP, less-than-prethreshold ROP, and no disease for each of 3 birth
      weight classes (<750 g, 750 to 999 g, and 1000 to 1250 g) of infants born between
      July 1, 1995, and June 30, 1996, and cared for in the Vanderbilt Neonatal
      Intensive Care Unit. We then compared these with the rates from our institution
      during the Cryo-ROP study recruitment period (January 1, 1986, to November 30,
      1987). RESULTS: The current incidence and severity of ROP have decreased
      substantially overall and for each weight group compared with the 1986-87
      incidence (P < .001, Cochran-Mantel-Haenszel test). The incidence of "any ROP"
      decreased by 27% for infants with birth weights less than 750 g, by 51% for
      infants 750 to 999 g, and by 71% for infants 1000 to 1250 g. The incidence of
      "prethreshold or greater ROP" decreased by 70% for the 750 to 999 g and 77% for
      the 1000 to 1250 g weight groups. Although the decrease in "prethreshold or
      greater ROP" was not as dramatic (25%) for the infants less than 750 g, only 1
      infant (10%) progressed to threshold disease in this group, whereas 7 (47%) did
      in 1986-87. The incidence of threshold ROP decreased by 84% for infants less than
      750 g and by 66% for infants 750 to 999 g. No infant with birthweight greater
      than 999 g progressed to threshold ROP. CONCLUSIONS: The incidence of all levels
      of ROP has decreased substantially for all infants with birth weights less than
      1251 g at Vanderbilt University Medical Center during the past decade. Putative
      factors responsible for this decrease may include surfactant use, continuous
      pulse oximetry, aggressive use of antenatal steroids, and improved neonatal
      nutritional support.

PMID- 10071902
TI  - Pediatric tetracycline-induced pseudotumor cerbri.
AB  - BACKGROUND: Tetracyclines have long been recognized as a cause of pseudotumor
      cerebri in adults, but the role of tetracyclines in the pediatric age group has
      not been well characterized in the literature and there have been few reported
      cases. We present 6 cases to better delineate the problem, the patient profile,
      the response to treatment, and the sequelae. METHODS: We retrospectively analyzed
      the records of all patients admitted with a diagnosis of pseudotumor cerebri who
      had documented usage of a tetracycline-class drug immediately before presentation
      at the Hospital For Sick Children in Toronto, Canada, from January 1, 1986, to
      March 1, 1996. RESULTS: Six patients (5 female, 1 male) who met all inclusion and
      exclusion criteria were identified; their ages ranged from 12 to 17 years. All
      were being treated for acne vulgaris. Duration of use before diagnosis was as
      short as 2 weeks and as long as 10 months, with a mean of 4.4 months. Duration of
      symptoms ranged from 0.57 to 4 weeks. Symptoms included headache (6 of 6), nausea
      (5 of 6), and diplopia (4 of 6). All for whom height and weight data were known
      (5 of 6) were in the upper quartile for body mass index. Visual acuity was 6/6 in
      all but 1 eye of one patient (6/9) at diagnosis, and final visual acuity was 6/6
      in all patients. All had normal color vision, where this was recorded (5 of 6).
      The only recorded field defect was enlargement of the blind spot (4 of 6). All
      patients responded to treatment, with loss of symptoms in 1 day to 4 weeks.
      CONCLUSIONS: Pseudotumor cerebri as a result of tetracycline-class drugs does
      occur in the pediatric population. With prompt and appropriate medical treatment,
      long-term sequelae can almost always be avoided. Physicians who treat patients
      with tetracyclines need to be aware of the potential complications in children.

PMID- 10071903
TI  - Normal visual development after unilateral complete ptosis at birth.
AB  - We report on a 5-year-old boy who was born with a unilateral complete ptosis
      secondary to a lid hematoma sustained at birth, which resolved spontaneously over
      the course of 6 weeks. Visual acuity and binocularity have developed normally.
      This case adds evidence to the proposal of a latent period before the onset of a
      sensitive period in visual development.

PMID- 10071904
TI  - Eyelid pruritus with intravenous morphine.
AB  - The cause of eyelid pruritus (itching) may be difficult to determine,
      particularly in preverbal children. Tearing, photophobia, or eye rubbing may be
      the first manifestation of leukemic infiltration or graft-versus-host disease,
      necessitating early appropriate therapy. We report a child in whom persistent eye
      rubbing developed after bone marrow transplantation for leukemia. Morphine
      administration was found to be the cause of this symptom.

PMID- 10071905
TI  - Hypobaric ocular trauma from a Popper.
AB  - We have observed 3 cases of ocular trauma in children that were caused by an
      atypical, hypobaric mechanism induced by a toy called a Popper. When we initially
      notified the United States Consumer Product Safety Commission in 1990, Poppers
      disappeared from store shelves. We are concerned that this potentially harmful
      toy is making a comeback in 1998 (Smilemakers Inc, Spartanburg, SC; June-July
      1998 catalog, p. 57). In 1990, packaged poppers cautioned against applying to
      face or skin; we are not sure that such warnings accompany current Poppers.

PMID- 10071906
TI  - Site-specific skeletal effects of exercise: importance of interstitial fluid
      pressure.

PMID- 10071907
TI  - Differential effect of treadmill exercise on three cancellous bone sites in the
      young growing rat.
AB  - The aim of the present study was to examine cancellous bone changes induced by
      exercise on three different skeletal sites, the lumbar vertebra, the proximal,
      and the distal tibia, in the young growing rat. Forty 4-week-old female Sprague
      Dawley rats were randomized into 4 groups of 10 animals each; 8 weeks exercise
      (8EX), 8 weeks sedentary control (8CON), 12 weeks exercise (12EX), and 12 weeks
      sedentary control (12CON). The exercise regimen consisted of treadmill running at
      24 m/min 1 hr per day 5 days a week. After each period of exercise, the proximal
      and distal tibial metaphyses (PTM and DTM, respectively) and the fifth lumbar
      (L5) vertebral body were processed for histomorphometry of the cancellous bone
      (secondary spongiosa) and cortical periosteum. Eight and twelve weeks of exercise
      significantly increased the mineral apposition rate and bone formation rate in
      the PTM and DTM, and 12 weeks of exercise significantly increased the labeled
      perimeter in the DTM, compared with the age-matched controls. Eight and twelve
      weeks of exercise significantly increased cancellous bone volume in the PTM (mean
      +/- standard deviation, 8EX; 19.1 +/- 2.9% vs 8CON; 14.3 +/- 3.1%, P < 0.05 and
      12EX; 18.8 +/- 3.5% vs 12CON; 15.2 +/- 3.3%, P < 0.05), and 12 weeks exercise
      significantly increased cancellous bone volume in the DTM, compared with age
      matched control (12EX; 32.5 +/- 7.7%, 12CON; 22.2 +/- 4.8%, P < 0.05). The
      increase in cancellous bone volume by 12 weeks exercise was higher in the DTM
      than that in the PTM (43.4% and 24.0%, respectively). On the other hand, the
      exercise did not significantly affect cancellous bone volume and bone formation
      in the L5 vertebral body, although the cortical periosteal bone formation rate
      and the L5 vertebral bone mass were increased. These findings suggest that
      cancellous bone adaptation to treadmill exercise is site specific, and the effect
      may be influenced by factors such as mechanical loading and metaphyseal bone
      architecture in the young growing rat.

PMID- 10071908
TI  - Femoral vein ligation increases bone mass in the hindlimb suspended rat.
AB  - Bone remodeling in response to changing mechanical demands is well recognized. It
      has been hypothesized that alterations in interstitial fluid flow (IFF), due to
      intraosseous pressure changes, influence bone remodeling. The goal of this study
      was to investigate the role of IFF in bone in the absence of mechanical strain
      using an in vivo model, the hindlimb suspended rat. Bone remodeling was assessed
      by direct measurements of weight, dimensions, bone mineral content (BMC) and bone
      mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA), and trabecular
      density using peripheral computed tomography (pQCT). Ligation of one femoral vein
      was performed as a means to alter the IFF within the ipsilateral femur; the
      contralateral limb was sham-operated as control. Animals were suspended for a
      period of 19 days. Intramedullary pressure in the venous-ligated femurs increased
      relative to the sham-operated control femurs (27.8 mmHg vs. 16.4 mmHg, p < 0.05),
      suggesting venous ligation increased IFF proportional to the pressure drop across
      the bone. Bone mineral content (BMC), when normalized to body weight, increased
      significantly in the venous-ligated femurs relative to control limbs (115.9 +/-
      15.6% vs. 103.8 +/- 13.2%, p < 0.001); similarly, gains in length (106.2 +/- 2.4%
      vs. 104.5 +/- 2.1%, p < 0.05) and distal width (110.8 +/- 10.3% vs. 106.2 +/-
      8.2%, p < 0.05) for the femurs with venous ligation were significantly greater
      relative to sham control. Furthermore, trabecular density was significantly
      higher in the femurs with venous ligation (351 +/- 12 g/cm3 vs. 329 +/- 11 g/cm3,
      p < 0.05). Daily administration of the cyclooxygenase inhibitor, indomethacin,
      via drinking water, suppressed the length increases observed for the venous
      ligated femur, suggesting a role for prostaglandins in IFF-mediated remodeling.
      These results suggest that IFF can directly influence bone adaptation independent
      of mechanical loading, and supports the hypothesis that fluid flow modulates bone
      remodeling.

PMID- 10071909
TI  - Expression and functional role of nitric oxide synthase isoforms in human
      osteoblast-like cells.
AB  - Previous studies have shown evidence of constitutive and cytokine-inducible
      nitric oxide (NO) synthase activity in cultured osteoblast-like cells from
      various species. Although cytokine-induced NO production has been found to
      inhibit osteoblast growth, the role of constitutive NO production in regulating
      osteoblast function is less clear and the isoforms of nitric oxide synthase (NOS)
      that are expressed by human osteoblasts have not been determined. Here, we
      investigated NOS expression in cultured human osteoblast-like cells and studied
      the effects of constitutive and cytokine-induced NO on osteoblast growth and
      differentiation. Low levels of NO were produced constitutively by osteoblast-like
      cells as reflected by analysis of medium nitrite concentrations, and evidence of
      ecNOS mRNA, protein, and bioactivity was found in primary osteoblasts (hOBs),
      TE85, and MG63 osteosarcoma cells. None of the osteoblast-like cells expressed
      nNOS, however, and iNOS was produced only by hOB cells after stimulation with the
      cytokines IL-1beta, TNF-alpha, and IFN-gamma. The NOS inhibitor, L-NMMA, did not
      affect growth or alkaline phosphatase activity in unstimulated osteoblasts.
      Incubation of hOB cells with cytokines inhibited growth and stimulated alkaline
      phosphatase activity and these effects were abrogated by L-NMMA. Cytokines also
      inhibited growth of TE85 cells and MG63 cells, but these effects appeared to be
      NO independent because they were not influenced by L-NMMA. Our experiments show
      that human osteoblasts constitutively produce NO through the ecNOS pathway, but
      demonstrate that this does not appear to exert an appreciable effect on
      osteoblast growth or differentiation under basal conditions. In contrast, IL
      1beta, TNF-alpha, and IFN-gamma exerted growth-inhibiting and differentiation
      inducing effects on osteoblasts that were partly NO dependent, indicating that NO
      may act predominantly as a modulator of cytokine-induced effects on osteoblast
      function.

PMID- 10071910
TI  - Effect of ED-71 on modeling of bone in distraction osteogenesis.
AB  - We investigated the effect of 2-beta-(3-hydroxypropoxy)-1alpha,25
      dihydroxyvitamin D3 (ED-71) on the modeling of bone in distraction osteogenesis.
      The tibiae of 30 rabbits were lengthened by 10 mm in 10 days. Following
      osteotomy, ED-71 (0.05 microg/kg) was administered subcutaneously twice a week to
      the ED-71 group until necropsy. The bone mineral content (BMC) of the lengthened
      callus was measured by dual-energy X-ray absorptiometry (DXA). Five rabbits per
      group were killed at 1, 3, and 8 weeks after completion of lengthening, and the
      lengthened callus was examined histologically and histomorphometrically. Bone
      volume of the lengthened callus was measured by peripheral quantitative computed
      tomography (pQCT) at 8 weeks after the completion of lengthening. At all
      timepoints the BMC in the ED-71 group was significantly higher than that in the
      untreated group. The mineral apposition rate and bone formation rate were higher
      in the ED-71 group than in the untreated group at 1 and 3 weeks after the
      completion of lengthening on the coronal section. In cross sections, the cortical
      area and width in the ED-71 group showed significantly higher values than in the
      untreated group at 8 weeks after the completion of lengthening. Both the
      endosteal osteoid surface and endosteal eroded surface showed no differences
      between groups. However, the endosteal mineral apposition rate and endosteal bone
      formation rate were significantly higher in the ED-71 group. At 8 weeks after
      completion of lengthening, the intracortical area and intracortical BMC were
      significantly greater in the ED-71 group than in the untreated group, but no
      significant difference was noted in intracortical BMD. These findings indicate
      that ED-71 increases callus volume during the early period after the completion
      of lengthening, resulting in thick cortical bone formation.

PMID- 10071911
TI  - Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of
      segmental bone defect in rabbits: a comparison with bone marrow and autologous
      cortical bone implantation.
AB  - Gastrectomy often results in increased likelihood of osteoporosis, metabolic
      aberration, and risk of fracture, and there is a need for a gastric peptide with
      osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound
      and fracture healing in rats in addition to having an angiogenic effect.
      Therefore, in the present study, using a segmental osteoperiosteal bone defect
      (0.8 cm, in the middle of the left radius) that remained incompletely healed in
      all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide
      BPC-157 was further studied (either percutaneously given locally [10 microg/kg
      body weight] into the bone defect, or applied intramuscularly [intermittently, at
      postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously
      [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]).
      For comparison, rabbits percutaneously received locally autologous bone marrow (2
      mL, postoperative day 7). As standard treatment, immediately after its formation,
      the bone defect was filled with an autologous cortical graft. Saline-treated (2
      mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals
      were used as controls. Pentadecapeptide BPC-157 significantly improved the
      healing of segmental bone defects. For instance, upon radiographic assessment,
      the callus surface, microphotodensitometry, quantitative histomorphometry (10
      microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10
      ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was
      shown to correspond to improvement after local application of bone marrow or
      autologous cortical graft. Moreover, a comparison of the number of animals with
      unhealed defects (all controls) or healed defects (complete bony continuity
      across the defect site) showed that besides pentadecapeptide intramuscular
      application for 14 days (i.e., local application of bone marrow or autologous
      cortical graft), also following other pentadecapeptide BPC-157 regimens (local
      application, or intermittent intramuscular administration), the number of animals
      with healed defect was increased. Hopefully, in the light of the suggested
      stomach significance for bone homeostasis, the possible relevance of this
      pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of
      unwanted effects) could be a basis for methods of choice in the future management
      of healing impairment in humans, and requires further investigation.

PMID- 10071912
TI  - Influence of skeletal site of origin and donor age on 1,25(OH)2D3-induced
      response of various osteoblastic markers in human osteoblastic cells.
AB  - Age-related bone loss may be a consequence of a lack of osteoblastic formation
      and/or function. In vitro, the osteoblastic response to 1,25(OH)2D3, an important
      regulator of osteoblastic function, appears to depend on the stage of
      osteoblastic maturation. In this study, we examined the response to 1,25(OH)2D3
      of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and
      osteocalcin (OC) secretion in primary cultures of osteoblastic cells from human
      trabecular bone (hOB). Forty-four bone samples were obtained from subjects
      undergoing knee arthroplastia, 20 aged 50-70 (64 +/- 5), and 24 >70 (73 +/- 2)
      years. Another 33 bone samples were obtained from subjects undergoing hip
      arthroplastia, 21 were aged 50-70 (64 +/- 4) and 12 >70 (75 +/- 5) years. Pooling
      knee and hip hOB cell cultures, we found that PICP secretion decreased after
      1,25(OH)2D3 in hOB cells from the older group (>70 years). Treatment with
      1,25(OH)2D3 increased ALP secretion in these cells only in the younger group (50
      70 years), whereas it increased OC secretion in hOB cells in both age groups. By
      pooling hOB cell cultures from both age groups we found that knee hOB cells
      increased OC secretion, and decreased PICP secretion, after 1,25(OH)2D3. This
      metabolite also increased OC secretion in hip hOB cells. Considering the
      influence of donor age at the same skeletal site, 1,25(OH)2D3 was found to
      stimulate ALP secretion only in knee hOB cells in the younger group. In contrast,
      this metabolite decreased ALP secretion in hip hOB cells in the older group. PICP
      secretion decreased after 1,25(OH)2D3 only in hOB cells in the older group, at
      both skeletal sites. In age-matched cultures, OC secretion was lower in hip hOB
      cells compared with those from the knee in the older group, but was similar in
      these cell cultures from both skeletal sites in the younger group. OC secretion
      after 1,25(OH)2D3 stimulation did not show age differences in knee hOB cells, but
      was lower in hip hOB in the older group. In summary, our results demonstrate that
      the response of various osteoblastic markers to 1,25(OH)2D3 in primary cultures
      of hOB cells depends on the donor age and skeletal site of origin.

PMID- 10071913
TI  - BMP-5 deficiency alters chondrocytic activity in the mouse proximal tibial growth
      plate.
AB  - The role of bone morphogenetic protein-5 (BMP-5) in regulating chondrocytic
      activity during endochondral ossification was examined in the mouse proximal
      tibial growth plate. Short ear mice homozygous for the SEA/Gn point mutation in
      the coding region for BMP-5 (King, J. A. et al. Dev Biol 166:112122; 1994) and
      heterozygous long ear littermates were examined at 5 and 9 weeks of age (n =
      9/group, four groups). Animals were injected with oxytetracycline to estimate the
      rate of growth and with bromodeoxyuridine to identify proliferative chondrocytes.
      Age-related changes in chondrocytic stereological and kinetic parameters were
      compared by image analysis of 1-microm-thick growth plate sections. The number of
      proliferative chondrocytes did not vary with age in either genotype, but
      proliferative phase duration increased significantly (approximately 67%) with age
      in the long ear mice, whereas no change was detected in the short ear mice. The
      number of hypertrophic chondrocytes increased significantly (approximately 27%)
      in the short ears, whereas this number decreased significantly (approximately
      40%) in the long ears. There was a small, but significant, increase in
      hypertrophic phase duration (approximately 45%) in short ear mice, but no change
      was detected in the long ears. These results indicate that BMP-5 deficiency
      prevents age-related decelerations in chondrocytic proliferation and initiation
      of hypertrophic differentiation, suggesting a role of BMP-5 in inhibiting these
      processes.

PMID- 10071914
TI  - Effect of interleukin-6 secreted by engineered human stromal cells on osteoclasts
      in human bone.
AB  - The effect of elevated human IL-6 (hIL-6) production by human bone marrow (Hu-BM)
      stromal cells on osteoclasts in human bone was examined. Human bone was implanted
      into nonobese diabetic mice with severe combined immunodeficiency (Hu-Bone
      NOD/SCID mice). Immunohistochemistry of bone implants and mouse spleens (at 20
      weeks), showed human CD45+ cells, B cells, and macrophages in both tissues. Thus,
      Hu-BM cells survive human bone transplantation and infiltrate mouse tissue. Bone
      implants had 75 +/- 12% (mean +/- SD) human CD45+ cells, and 9 +/- 4% mouse
      hematopoietic cells. A retrovirus vector containing the human IL-6 gene was used
      to transduce Hu-BM stromal cells (IL-6/stromal) and the PA317 cell line (IL
      6/PA317). IL-6/ stromal cells (secreting, on average, 17 microg of hIL-6/10(6)
      cells per 24 h) were injected directly into human bone implants in Hu-Bone
      NOD/SCID mice. IL-6/PA317 cells (secreting 16 microg/mL of hIL-6/10(6) cells per
      24 h) were injected intraperitoneally into Hu-Bone-NOD/SCID mice. Analyses of
      sera from both groups of animals showed elevated levels of IL-6. However, only
      bone implants engrafted with IL-6/stromal cells had a statistically significant
      increase in osteoclast-lined mineralized trabecular bone surface (BS). Thus, a
      high concentration of serum hIL-6 in Hu-Bone-NOD/SCID mice alone does not
      increase osteoclast-lined BS in bone implants. Most importantly, it is the type
      of human BM cell that secretes the high levels of hIL-6 that is most critical.

PMID- 10071915
TI  - Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) distribution in normal
      and pathological human bone.
AB  - Degradation of skeletal connective tissue is regulated, at least in part, by the
      balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinase (TIMPs), their natural inhibitors. The balance between MMPs and
      TIMPs may therefore be a determinant of normal bone turnover, and imbalance could
      thus lead to reduced organization of bone structure. To test this hypothesis, the
      cellular expression of MMPs and TIMP-1 was investigated by immunohistochemistry
      in human neonatal rib and osteophytic and heterotopic bone; these differ in their
      structure, with heterotopic bone showing the least and normal rib the most
      organized development. In all samples, high levels of MMPs were expressed.
      Collagenase and stromelysin-2 were detected in chondrocytes, osteoblasts, and
      osteoclasts, whereas gelatinase-B was confined to osteoclasts and mononuclear
      cells. Matrix-associated stromelysin-1 was present in fibrous tissue and osteoid.
      In contrast, the expression of TIMP-1 varied markedly between the three types of
      bone. In heterotopic bone only occasional low level TIMP-1 expression was
      detected in chondrocytes and osteoblasts. Osteophytic bone showed varying levels
      of TIMP-1, which was matrix-bound in fibrous tissue and cell-associated in
      osteoblasts, chondrocytes, and occasional mononuclear cells. In both types of
      bone, expression of TIMP-1 by osteoclasts was absent despite large numbers of
      these cells. Neonatal rib bone showed consistent expression of TIMP-1,
      particularly in chondrocytes, osteoblasts, and lining cells. In contrast to
      pathological bone, many osteoclasts were TIMP-1 positive. These results suggest
      that, in heterotopic and osteophytic bone, the low levels of TIMP-1, and in
      particular its absence in osteoclasts, may partly explain the more poorly
      organized bone formation in these pathological bone samples. Furthermore, TIMP-1
      may play a role in the regulation of bone modeling and remodeling in normal
      developing human bone.

PMID- 10071916
TI  - Biochemical markers can predict the response in bone mass during alendronate
      treatment in early postmenopausal women. Alendronate Osteoporosis Prevention
      Study Group.
AB  - Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate
      in the prevention of postmenopausal osteoporosis were used to evaluate the
      capacity of the biochemical markers to predict changes in bone mineral density
      (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin
      (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline
      phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and
      uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and
      deoxypyridinoline (dPyr). The correlation between change from baseline at months
      3-12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD
      ranged from r = -0.45 to r = -0.78 (p < 0.001), and from r = -0.38 to r = 0.10
      (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to
      assess the accuracy of change from baseline at month 6 in the biochemical markers
      for predicting prevention of bone loss in the spine over 2 years. The cutpoints
      used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline.
      Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and
      89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71%
      (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total
      OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive
      capacities of change from baseline at year 2 in hip BMD in predicting prevention
      of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and
      positive predictive value, 79%. In conclusion, short-term changes in biochemical
      markers were valid predictors of long-term changes in BMD. Short-term changes in
      the sensitive biochemical markers revealed a predictive capacity similar to bone
      densitometry at the hip measured over 2 years. The sensitive biochemical markers
      offered a fast and valid alternative to bone densitometry for monitoring of
      alendronate treatment.

PMID- 10071917
TI  - Early effects of hormone replacement therapy on bone.
AB  - Estrogen replacement is currently the preferred therapy for postmenopausal
      osteoporosis, although its mechanism of action remains poorly understood. Its
      primary action on bone is generally considered to be antiresorptive, but there is
      evidence in animals to suggest a stimulatory effect on bone formation. We have
      now attempted to detect a similar effect in humans by administering hormone
      replacement therapy (estradiol valerate 2 mg/day and dydrogesterone 5 mg/day
      given in a continuous, combined manner) to ten postmenopausal women. We carried
      out histomorphometric analyses of transiliac bone biopsies after quadruple
      tetracycline labeling, which was commenced before and continued during the first
      4 weeks of hormone replacement therapy. Biochemical markers of bone turnover
      suggested that bone resorption decreased, but no significant effects on
      histomorphometric parameters of bone formation were detected. We conclude that
      hormone replacement therapy at the dose given does not stimulate bone formation
      in the iliac crest as assessed by histomorphometry.

PMID- 10071918
TI  - Osteoporosis in adult patients with celiac disease.
AB  - We investigated the bone mineral density (BMD) and prevalence of osteopenia and
      osteoporosis in adult celiac patients with varying disease states. In this cross
      sectional study the data on the severity of celiac disease and BMD were collected
      from 77 celiac patients (28 newly diagnosed and 49 previously diagnosed celiac
      patients), and BMD results were compared with those of 157 control subjects
      matched for age, gender, and menopausal status. The celiac patients had
      significantly lower BMD than the control subjects at the lumbar spine (-6%) and
      femoral neck (-5%). The mean BMD did not differ significantly among celiac
      patients classified by severity of disease. Based on Z scores, 35% of the celiac
      patients and 17% of the control subjects had low BMDs for age at the lumbar spine
      (p = 0.005), whereas 31% of celiac patients and 16% of control subjects had Z
      scores of < or =-1 at the femoral neck (p = 0.01). Altogether, 26% of all celiac
      patients, but only 5% of control subjects, were classified as having osteoporosis
      (T score < or =-2.5 SD) at the lumbar spine (p = 0.03), whereas osteoporosis was
      rare at the femoral neck in both groups (3% vs. 1%, p = 1.00). Prevalence of
      osteopenia and osteoporosis was highest in newly diagnosed celiac patients and in
      patients with disease not in remission. A low 25-(OH)D vitamin concentration was
      a typical biochemical abnormality in our patients (64% of men and 71% of women).
      The main associated variables of low BMD were age (men), low serum vitamin D
      level, low body weight, and postmenopausal status (women). The present study
      suggests that celiac disease constitutes a risk factor for osteoporosis. This
      finding applies particularly to untreated and poorly treated patients.

PMID- 10071919
TI  - The changing picture of hip fractures: dramatic change in age distribution and no
      change in age-adjusted incidence within 10 years in Central Finland.
AB  - The objective of this study was to find out if the age-standardized incidence of
      hip fractures has changed in 10 years in Central Finland. Patients with acute hip
      fracture admitted to Jyvaskyla Central Hospital in 1982-1983 (n = 317) and in
      1992-1993 (n = 351) were selected from the hospital discharge register and from
      contemporaneous records of the Department of Anesthesiology and the ward of
      traumatology. Earlier studies in Finland have indicated that there has been an
      increase in incidence rates. The results of this study show no change in the age
      standardized incidence of hip fractures of men and women during the last 10
      years. However, because of the change in the age distribution of the population,
      the number of hip fractures has increased by 11%. The mean age of the hip
      fracture patients increased from 75.4 years in 1982-1983 to 78.4 years in 1992
      1993. In 1982-1983, 18.0% of the patients were > or =85 years. The corresponding
      figure in 1992-1993 was 30.2%. Therefore, we summarize that there has been a
      dramatic change in age distribution and no change in age-adjusted incidence
      within the last 10 years in central Finland.

PMID- 10071920
TI  - Spatial relationships between prevalent and incident spine fractures.
AB  - Women with prevalent fractures have an increased risk of developing additional,
      incident fractures. This article examines the relation between the location of
      prevalent fractures within the spine and the risk of subsequent vertebral
      fractures. The subjects were 721 Japanese-American women of mean age 69.5 +/- 5.3
      (SD) years. For the analyses, the spine was categorized into three regions: an
      upper region, vertebrae T3-11; a middle region, vertebrae T-12 and L-1; and a
      lower region, vertebrae L2-5. Initial analyses were limited to women with, at
      most, one prevalent fracture. Compared to women without fracture, women with a
      prevalent fracture had odds ratios of 2-5 for developing an incident fracture
      outside the prevalent region. Subsequent analyses included women with multiple
      prevalent fractures. Women having two or three prevalent fractures had odds
      ratios of 7-9 for developing an incident fracture outside the prevalent region.
      The results suggest that the increased fracture risk of women with prevalent
      fractures extends beyond nearby vertebrae, and can affect vertebrae both above
      and below the prevalent fracture.

PMID- 10071921
TI  - Changing incidence of hip, distal radius, and proximal humerus fractures in
      Tottori Prefecture, Japan.
AB  - A survey of all fractures in patients > or =35 years of age for hip, distal
      radius, and proximal humerus was performed in Tottori Prefecture, Japan. Hip
      fracture survey was done for the years 1986-1988, and also 1992-1994. A distal
      radius and proximal humerus fracture survey was done for the years 1986-1988,
      1992, and 1995. The age- and gender-specific incidence rates of these three types
      of fracture among Japanese were substantially lower than those of whites living
      in North America or northern Europe. The age-adjusted incidence rates of hip
      fracture (per 100,000 person-years) were 40.7 and 114.1 in 1986 and 57.1 and
      145.2 in 1994 for men and women, respectively, showing a significant increase
      with time for women. Upon examination of individual fracture types, there was no
      significant increase in cervical fractures, whereas a significant increase was
      observed in trochanteric fractures for women. The age-adjusted incidence rates of
      distal radius fractures for women were 164.9 in 1986 and 211.4 in 1995, showing a
      significant increase with time; however, no increase was observed among men.
      Incidence of proximal humerus fractures was 10.3 and 42.0 in 1986 and 17.1 and
      47.9 in 1995 for men and women, respectively, and these increases were
      significant for both genders.

PMID- 10071922
TI  - Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in
      disabled elderly stroke patients.
AB  - A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related
      increased serum calcium concentration have been observed in hemiplegic stroke
      patients. To elucidate the influence of increased serum calcium concentration on
      bone metabolism, we measured serum biochemical indices and bone mineral density
      (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke
      and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D
      [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH),
      intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal
      telopeptide of type I collagen (ICTP) were measured. An increased serum calcium
      concentration (mean 2.543 mEq/L) was observed in this population and correlated
      negatively with the Barthel index (mean 66), indicating immobilization-induced
      bone resorption with consequent increased serum calcium. Decreased serum
      concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration
      (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L).
      Serum levels of BGP were decreased significantly, whereas serum ICTP
      concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was
      seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of
      the second metacarpal in patients was decreased significantly compared with
      control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D
      concentrations. Immobilization-related increased serum calcium levels may inhibit
      PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D
      insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.

PMID- 10071923
TI  - Chemical cleavage of bovine beta-lactoglobulin by BNPS-skatole for preparative
      purposes: comparative study of hydrolytic procedures and peptide
      characterization.
AB  - A comparative study of various procedures for tryptophanyl peptide bond cleavage
      by BNPS-skatole [2-(2-nitrophenyl)-3-methyl-3-bromoindolenine] was carried out on
      native and on reduced and alkylated bovine beta-lactoglobulin (BLG). The reaction
      yield and the composition of the derived products were studied in acetic acid,
      trifluoroacetic acid (TFA), and ethanol/TFA. For BNPS-skatole removal, extraction
      by water or ethyl ether was compared with dialysis and gel filtration. The three
      expected peptides (1-19, 20-61, 62-162) and incomplete cleaved fragments (1-61,
      20-162) were separated and characterized by electrophoresis, reverse-phase high
      performance liquid chromatography, and mass spectrometry. The highest hydrolysis
      yield (67.4%) occurred with native BLG cleaved in 88% acetic acid at 47 degrees C
      for 60 min. Subsequent water extraction and gel filtration led to total recovery
      of the material, but reagent elimination was only quantitative after gel
      filtration. Cleavage specificity was ensured by mass spectrometry and the amino
      acid composition of peptides 1-19 and 62-162. The chemical side reactions
      identified are discussed.

PMID- 10071924
TI  - Evolution of phosphagen kinase VII. Isolation of glycocyamine kinase from the
      polychaete Neanthes diversicolor and the cDNA-derived amino acid sequences of
      alpha and beta chains.
AB  - Glycocyamine kinase (GK) was isolated from the marine polychaete Neanthes
      diversicolor by gel filtration, DEAE-cellulose chromatography, butyl-Toyopearl
      hydrophobic chromatography, and chromatofocusing. The GK was eluted as a single
      peak on the latter three chromatographies, and the molecular mass for the native
      GK was estimated to be about 80 kDa. The SDS-PAGE showed that the isolated GK
      consists of two distinct subunits in equal proportion, alpha and beta chains,
      with molecular masses of 42.2 and 43.8 kDa, respectively. The present results
      suggest that the Neanthes GK has a heterodimeric structure. The cDNAs for alpha
      and beta chains of Neanthes GK were amplified by PCR and their cDNA-derived amino
      acid sequences were determined. The alpha and beta chains are composed of 374 and
      390 amino acids, and the molecular masses were calculated to be 42,392 and 43,966
      Da, respectively, in good agreement with the apparent masses on SDS PAGE. The
      beta chain has a characteristic N-terminal extension of 15 amino acids, and all
      of the sequence differences between alpha and beta chains were restricted in the
      N-terminal region of 50 residues. The overall sequence identity was 92%. The
      occurrence of heterodimeric nature in Neanthes GK is of great interest from the
      evolutionary point of view, because the heterodimeric structure is only known for
      creatine kinase MB-isozyme specific for mammalian heart muscle among phosphagen
      kinases.

PMID- 10071925
TI  - Bacillus intermedius glutamyl endopeptidase. Molecular cloning and nucleotide
      sequence of the structural gene.
AB  - The glutamyl endopeptidase gene of Bacillus intermedius was cloned from a genomic
      library expressed in Bacillus subtilis and sequenced (EMBL accession number
      Y15136). The encoded preproenzyme contains 303 amino acid residues; the mature 23
      kDa enzyme consists of 215 residues. The mature enzyme reveals 38% of identical
      residues when aligned with the glutamyl endopeptidase from Bacillus
      licheniformis, whereas only five invariant residues were found among all known
      glutamyl endopeptidases. The amino acid residues that form the catalytic triad
      (H47, D98, and S171) as well as H186 participating in the binding of the
      substrate carboxyl group were identified. It seems that the structural elements
      responsible for the function of glutamyl endopeptidases from various sources are
      highly variable.

PMID- 10071926
TI  - Molecular properties of a hemagglutinin purified from type A Clostridium
      botulinum.
AB  - Clostridium botulinum causes the food poisoning disease botulism by producing
      botulinum neurotoxin, the most potent toxin known. The neurotoxin is produced
      along with a group of neurotoxin-associated proteins, or NAPs, which protect it
      from the low pH and proteases of the gastrointestinal tract. Recently, we
      isolated one of the major components of NAPs, a 33-kDa hemagglutinin (Hn-33) [Fu
      et al. (1998), J. Protein Chem. 17, 53-60]. In this study, we present molecular
      properties of Hn-33 derived from several biochemical and biophysical techniques.
      Hn-33 in pure form requires a 66-fold lower concentration of sugar inhibition of
      its hemagglutination activity than in its complexed form with the neurotoxin and
      other NAPs. However, its protease resistance is not affected by sugar binding.
      Based on FT-IR and circular dichroism (CD) analysis, Hn-33 is a predominantly
      beta-sheet protein (74-77%). Hn-33 analysis by laser desorption mass spectrometry
      and size exclusion column chromatography reveals that it exists predominantly in
      a dimeric form in the aqueous solution. Even a very low concentration of SDS
      (0.05%) irreversibly destroyed the biological activity of Hn-33 by changing its
      secondary structure as revealed by far-UV CD analysis.

PMID- 10071927
TI  - Protein structure prediction in a 210-type lattice model: parameter optimization
      in the genetic algorithm using orthogonal array.
AB  - We have applied the orthogonal array method to optimize the parameters in the
      genetic algorithm of the protein folding problem. Our study employed a 210-type
      lattice model to describe proteins, where the orientation of a residue relative
      to its neighboring residue is described by two angles. The statistical analysis
      and graphic representation show that the two angles characterize protein
      conformations effectively. Our energy function includes a repulsive energy, an
      energy for the secondary structure preference, and a pairwise contact potential.
      We used orthogonal array to optimize the parameters of the population, mating
      factor, mutation factor, and selection factor in the genetic algorithm. By
      designing an orthogonal set of trials with representative combinations of these
      parameters, we efficiently determined the optimal set of parameters through a
      hierarchical search. The optimal parameters were obtained from the protein
      crambin and applied to the structure prediction of cytochrome B562. The results
      indicate that the genetic algorithm with the optimal parameters reduces the
      computing time to reach a converged energy compared to nonoptimal parameters. It
      also has less chance to be trapped in a local energy minimum, and predicts a
      protein structure which is closer to the experimental one. Our method may also be
      applicable to many other optimization problems in computational biology.

PMID- 10071928
TI  - Purification and characterization of a proteinase inhibitor from field bean,
      Dolichos lablab perpureus L.
AB  - A proteinase inhibitor resembling Bowman-Birk family inhibitors has been purified
      from the seeds of cultivar HA-3 of Dolichos lablab perpureus L. The protein was
      apparently homogeneous as judged by SDS-PAGE, PAGE, IEF, and immunodiffusion. The
      inhibitor had 12 mole% 1/2-cystine and a few aromatic amino acids, and lacks
      tryptophan. Field bean proteinase inhibitor (FBPI) exhibited a pI of 4.3 and an
      Mr of 18,500 Da. CD spectral studies showed random coiled secondary structure.
      Conformational changes were detected in the FBPI-trypsin/chymotrypsin complexes
      by difference spectral studies. Apparent Ka values of complexes of inhibitor with
      trypsin and chymotrypsin were 2.1x10(7) M(-1) and 3.1x10(7) M(-1), respectively.
      The binary and ternary complexes of FBPI with trypsin and chymotrypsin have been
      isolated indicating 1:1 stoichiometry with independent sites for cognate enzymes.
      Amino acid modification studies showed lysine and tyrosine at the reactive sites
      of FBPI for trypsin and chymotrypsin, respectively.

PMID- 10071929
TI  - Kinetic and mutagenic evidence for the role of histidine residues in the
      Lycopersicon esculentum 1-aminocyclopropane-1-carboxylic acid oxidase.
AB  - The ACCO gene from Lycopersicon esculentum (tomato) has been cloned into the
      expression vector PT7-7. The highly expressed protein was recovered in the form
      of inclusion bodies. ACCO is inactivated by diethyl pyrocarbonate (DEPC) with a
      second-order rate constant of 170 M(-1) min(-1). The pH-inactivation rate data
      imply the involvement of an amino acid residue with a pK value of 6.05. The
      difference UV spectrum of the the DEPC-inactivated versus native ACCO showed a
      single peak at 242 nm indicating the modification of histidine residues. The
      inactivation was reversed by the addition of hydroxylamine to the DEPC
      inactivated ACCO. Substrate/cofactor protection studies indicate that both iron
      and ACC bind near the active site, which contains histidine residues. Four
      histidines of ACCO were individually mutated to alanine and glycine. H39A is
      catalytically active, while H177A, H177G, H211A, H211G, H234A, and H234G are
      basically inactive. The results indicate that histidine residues 177, 211, and
      234 may serve as ligands for the active-site iron of ACCO and/or may play some
      important structural or catalytic role.

PMID- 10071930
TI  - Localization of a single transglutaminase-reactive glutamine in the third domain
      of RAP, the alpha2-macroglobulin receptor-associated protein.
AB  - The 39-kDa receptor-associated protein (RAP) is an intracellular glycoprotein
      that interacts with hitherto unknown sites in several members of the low-density
      lipoprotein receptor gene family. Upon binding to these receptors, RAP inhibits
      all ligand interactions with the receptors. In the present study, the
      transglutaminase-catalyzed incorporation of radioactively labeled putrescine and
      a dansylated glutamine-containing peptide into human RAP has been studied. The
      results indicate the presence of both glutamine and lysine residues in RAP,
      accessible for transglutaminase cross-linking. Moreover, enzymatic digestion
      followed by sequence analysis of radiolabeled fractions demonstrated that Gln261
      acts as the amine acceptor site. This residue is located in the third domain of
      RAP and is conserved among the RAP interspecies homologues. Insertion of a
      reporter group into the protein could prove useful to assess ligand/receptor
      interactions.

PMID- 10071931
TI  - Protein sequence analysis using Hewlett-Packard biphasic sequencing cartridges in
      an applied biosystems 473A protein sequencer.
AB  - Protein sequence analysis using an adsorptive biphasic sequencing cartridge, a
      set of two coupled columns introduced by Hewlett-Packard for protein sequencing
      by Edman degradation, in an Applied Biosystems 473A protein sequencer has been
      demonstrated. Samples containing salts, detergents, excipients, etc. (e.g.,
      formulated protein drugs) can be easily analyzed using the ABI sequencer. Simple
      modifications to the ABI sequencer to accommodate the cartridge extend its
      utility in the analysis of difficult samples. The ABI sequencer solvents and
      reagents were compatible with the HP cartridge for sequencing. Sequence
      information up to ten residues can be easily generated by this nonoptimized
      procedure, and it is sufficient for identifying proteins by database search and
      for preparing a DNA probe for cloning novel proteins.

PMID- 10071932
TI  - Participation of chaperonin GroEL in the folding of D-glyceraldehyde-3-phosphate
      dehydrogenase. An approach based on the use of different oligomeric forms of the
      enzyme immobilized on sepharose.
AB  - The binding of denatured B. stearothermophilus D-glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) to the E. coli chaperonin GroEL was investigated in two
      systems: (1) GroEL immobilized on Sepharose via a single subunit was titrated
      with urea-denatured soluble GAPDH and (2) a Sepharose-bound denatured GAPDH
      monomer was titrated with soluble GroEL. Similar apparent KD values for the
      complex GroEL x GAPDH were obtained in both cases (0.04 and 0.03 microM,
      respectively), the stoichiometry being 1.0 mol chaperonin per GAPDH subunit in
      the system with the immobilized GroEL and 0.2 mol chaperonin per Sepharose-bound
      GAPDH monomer. Addition of GroEL and Mg x ATP to a reactivation mixture increased
      the yield of reactivation of both E. coli and B. stearothermophilus GAPDHs.
      Incubation of the Sepharose-bound catalytically active tetrameric and dimeric
      GAPDH forms with the protein fraction of a wild-type E. coli cell extract
      resulted in the binding of GroEL to the dimer and no interaction with the
      tetrameric form. These data suggest that GroEL may be capable of interacting with
      the interdimeric contact regions of the folded GAPDH dimers.

PMID- 10071933
TI  - In vitro translation of type A Clostridium botulinum neurotoxin heavy chain and
      analysis of its binding to rat synaptosomes.
AB  - Botulinum neurotoxins (BoNTs) are highly potent toxins that inhibit
      neurotransmitter release from peripheral cholinergic synapses. BoNTs consist of a
      toxifying light chain (LC; 50 kDa) and a binding/translocating heavy chain (HC;
      100 kDa) linked through a disulfide bond. A DNA fragment encoding type A
      Clostridium botulinum heavy chain (BoNT/A HC) was amplified by polymerase chain
      reaction and cloned into an E. coli PET-15b vector. In vitro translated
      [35S]BoNT/A HC was identified by anti-BoNT/A polyclonal antibodies, and was used
      to investigate the binding of the toxin to rat synaptosomes. The binding of
      [35S]BoNT/A HC to synaptosomes was abolished by 500-fold excess of cold BoNT/A,
      and by incubation with trypsin. Treatment of BoNT/A HC with anti-BoNT/A or G(T1b)
      blocked its binding to synaptosomes. The radioactive BoNT/A HC recognized three
      proteins corresponding to a molecular mass of 150 (P150), 120 (P120), and 75
      (P75) kDa in rat and bovine synaptosomal preparations. These results represent
      the first successful expression of functional full-length BoNT heavy chain.

PMID- 10071934
TI  - Interaction of Eu3+ with yeast alcohol dehydrogenase.
AB  - The activity of yeast alcohol dehydrogenase is markedly enhanced by Eu3+ ions. At
      pH 7.0 two binding constants for Eu3+, 1.0x10(-2) and 2.0x10(-3) microM, were
      obtained using a Scatchard plot. The presence of Zn2+ ions restricts the Eu3+ 
      induced increase in the activity of yeast alcohol dehydrogenase. Studies on the
      tryptophan fluorescence of the enzyme in the absence and presence of Eu3+ or Zn2+
      ions showed that Eu3+ affects tertiary or quaternary structures, which is
      consistent with its activation of the enzyme. The presence of Zn2+ reverses the
      conformational changes caused by Eu3+. Comparison of the effects of Eu3+ with
      Zn2+ for apo-yeast alcohol dehydrogenase indicates that their binding sites on
      the protein are different.

PMID- 10071935
TI  - Purification and properties of gammagamma-enolase from pig brain.
AB  - Isoelectric focusing revealed three enolase isoforms in pig brain, which were
      designated as alphaalpha-(pI = 6.5), alphagamma- (pI = 5.6), and gammagamma
      enolase (pI = 5.2). The pI of purified gammagamma-enolase was also 5.2. The
      gammagamma-enolase isoform of enolase was purified from pig brain by a
      purification protocol involving heating to 55 degrees C for 3 min, acetone
      precipitation, ammonium sulfate precipitation (40%-80%), DEAE Sephadex ion
      exchange chromatography (pH 6.2), and Sephadex G200 gel filtration. The final
      specific activity was 82 units/mg protein. As with other vertebrate enolases,
      gammagamma-enolase from pig proved to be a dimer with a native mass of 85 kDa and
      a subunit mass of 45 kDa. The pH optimum for the reaction in the glycolytic
      direction is 7.2. The Km values for 2-PGA, PEP, and Mg2+ were determined to be
      0.05, 0.25, and 0.50 mM, respectively, similar to Km values of other vertebrate
      enolases. The amino acid composition of pig gammagamma-enolase, as determined by
      amino acid analysis, shows strong similarity to the compositions of gammagamma
      enolases from rat, human, and mouse, as determined from their amino acid
      sequences. Despite the differences seen with some residues, and considering the
      ways that the compositions were obtained, it is assumed that pig gammagamma
      enolase is more similar than the composition data would indicate. Moreover, it is
      likely that the sequences of pig gammagamma-enolase and the other gammagamma
      enolases are almost identical. Li+ proved to be a noncompetitive inhibitor with
      either 2-PGA or Mg2+ as the variable substrate. This enolase crystallized in the
      monoclinic space group P2, or P2(1). An Rsymm <5% was obtained for data between
      50 and 3.65 A, but was a disappointing 30% for data between 3.65 and 3.10 A,
      indicating crystal disorder.

PMID- 10071936
TI  - Kinetics and equilibrium studies of Tet repressor-operator interaction.
AB  - Binding of a Tet repressor mutant containing a single Trp43 residue in the tet
      operator recognition alpha-helix leads to the quenching of the protein
      fluorescence down to about 23% in the case of the tet O1 operator and to 40% in
      the case of the tet O2 operator. We have used fluorescence detection to describe
      the binding equilibrium and kinetics of the Tet repressor interaction with the 20
      bp DNA operators tet O1 and tet O2. Stopped-flow measurements in an excess of the
      tet operators performed in 5 mM NaCl or 150 mM NaCl indicate that the reaction
      can be described by at least three exponentials characterized by different
      relaxation times. The mechanism of interaction for both operators as well as for
      two salt concentrations used can be described as TetR + Operator <==> Complex 1
      <==> Complex 2 <==> Complex 3. Only the much faster process can be described as a
      second-order reaction characterized by a bimolecular rate constant equal to
      2.8X10(6) M(-1) sec(-1) for both operators. The medium and slow processes may be
      described by relaxational times ranging from 50 msec to seconds. The results of
      the binding equilibrium measurements extrapolated to 1 M NaCl concentration,
      which reflects the specific nonionic interaction between TetR and tet operators,
      indicate Kas equal to 3.2x10(4) and 4.0x10(5) M(-1) for tet O1 and tet O2,
      respectively. The number of monovalent ions replaced upon binding can be
      calculated as about 5 and 3 for tet O1 and tet O2, respectively. The binding of
      Tet repressor to the operators leads to changes in the circular dichroism spectra
      of the DNA which could indicate transitions of B-DNA into A-like DNA structure.

PMID- 10071937
TI  - Properties of soluble fusions between mammalian aspartic proteinases and
      bacterial maltose-binding protein.
AB  - The mammalian aspartic proteinases procathepsin D and pepsinogen form insoluble
      inclusion bodies when expressed in bacteria. They become soluble but nonnative
      when synthesized as fusions to the carboxy terminus of E. coli maltose-binding
      protein (MBP). Since these nonnative states of the two aspartic proteinases
      showed no tendency to form insoluble aggregates, their biophysical properties
      were analyzed. The MBP portions were properly folded as shown by binding to
      amylose, but the aspartic proteinase moieties failed to bind pepstatin and lacked
      enzymatic activity, indicating that they were not correctly folded. When treated
      with proteinase K, only the MBP portion of the fusions was resistant to
      proteolysis. The fusion between MBP and cathepsin D had increased hydrophobic
      surface exposure compared to the two unfused partners, as determined by bis-ANS
      binding. Ultracentrifugal sedimentation analysis of MBP-procathepsin D and MBP
      pepsinogen revealed species with very large and heterogeneous sedimentation
      values. Refolding of the fusions from 8 M urea generated proteins no larger than
      dimers. Refolded MBP-pepsinogen was proteolytically active, while only a few
      percent of renatured MBP-procathepsin D was obtained. The results suggest that
      MBP-aspartic proteinase fusions can provide a source of soluble but nonnative
      folding states of the mammalian polypeptides in the absence of aggregation.

PMID- 10071938
TI  - Synthesis and biochemical characterization of obligatory dimers of the sugar non
      specific nuclease from Serratia marcescens using specifically designed
      bismaleimidoalkanes as SH-specific crosslinking reagents.
AB  - The genetically engineered S140C variant of the homodimeric nuclease from
      Serratia marcescens was crosslinked across the dimer interface at the Cys 140
      residues using bifunctional SH-specific 1,1'-alkanediyl-bis-pyrrole-2,5-diones of
      different lengths. These bismaleimidoalkanes were synthesized by the condensation
      of n-alkyldiamines with maleic anhydride and subsequent cyclization with acetic
      anhydride and sodium acetate. Bismaleimidohexane (BMH) which gave the best
      crosslinking yield was used to produce in preparative amounts crosslinked
      Serratia nuclease. The crosslinked protein has the same secondary structure and
      exhibits the same guanidinium chloride unfolding behavior as the wild type enzyme
      or the non-covalently linked S 140C variant. In contrast, in thermal unfolding
      experiments the crosslinked dimer behaves differently from the wild type enzyme
      or the non-covalently linked S140C variant. CD-spectra recorded during
      temperature rise showed only minor changes of the secondary structure composition
      for the wild type enzyme and the non-covalently linked S140C variant, whereas in
      the case of the crosslinked S140C dimer a distinct increase of the CD effect was
      observed corresponding to an increase in alpha-helix. Our results demonstrate
      that bismaleimidoalkanes are very well suited to covalently link subunits of
      proteins, provided suitably located cysteine residues are present.

PMID- 10071939
TI  - Cognitive performance at school age of very low birth weight infants with
      bronchopulmonary dysplasia.
AB  - The hypothesis was that bronchopulmonary dysplasia (BPD) adversely affects
      cognitive performance at school age. This prospective cohort study examined three
      groups of children at 8 to 10 years of age. Group 1 (n = 311) consisted of very
      low birth weight (VLBW) infants without BPD and Group 2 (n = 95) consisted of
      VLBW infants with BPD. Group 3 (n = 188) consisted of term infants without BPD.
      Regression analysis determined the effect of BPD on eight performance measures
      while controlling for possible confounding variables. Children in Group 3 had the
      best performance and children in Group 2 had the poorest performance on all
      measures. These differences were significant (p = .0001) for the Full Scale IQ,
      Performance IQ, and reading and math grades and ages. Children in Groups 3 and 1
      performed better than children in Group 2 for the Verbal IQ (p = .0001) and the
      Developmental Test of Visual-Motor Integration (p = .0012), but for these two
      measures there was no significant difference between children in Groups 3 and 1.
      Thus, poorer performance was found in VLBW infants with a history of BPD.

PMID- 10071940
TI  - Adaptation during early childhood among mothers of children with disabilities.
AB  - This study documents the extent to which child-related and parenting stress vary
      during the early childhood period among mothers of children with developmental
      disabilities. The degree to which specific aspects of the family environment
      predict stress levels measured at age 3 years and 5 years, after controlling for
      child characteristics and family income, is also investigated. The Parenting
      Stress Index was completed by 79 mothers of children with developmental
      disabilities at three time points: (1) within 1 month of the child's entry into
      an early intervention program (T1); (2) within 1 month of the child's third
      birthday (T3); and (3) within 1 month of the child's fifth birthday (T5). Data on
      child characteristics and family income as well as measures of the family
      environment (i.e., negative life events, cohesion, and family support) were
      gathered at both T1 and T3. Repeated measures analysis of variance was used to
      assess whether there was significant change in the child-related and parenting
      stress scores across the three time points. Two sets of hierarchical regression
      equations were also analyzed. The first examined which child, family, and family
      environment characteristics assessed at T1 predicted stress at T3. The second
      identified the predictors of T5 stress based on independent variables measured at
      T3. Child-related stress increased significantly across the three time points,
      whereas parenting stress remained fairly stable. By age 5 years, one-third of the
      mothers had child-related stress scores above the clinical cutoff point.
      Regression analyses revealed the importance of the family environment in
      predicting both stress outcomes. The only statistically significant predictor of
      child-related stress at T3 was family cohesion, whereas parenting stress at T3
      was predicted by income, cohesion, and family support. The predictors of both
      child-related and parenting stress at T5 were the same. Greater family cohesion
      and fewer negative life events predicted lower stress scores at T5. The
      significant increase in child-related stress during the early childhood period
      warrants attention by pediatricians, educators, and other professionals who must
      evaluate the needs of families of children with disabilities for supportive
      services. Aspects of the family environment were shown to be critical and
      consistent determinants of both child-related and parenting stress throughout the
      early childhood period. This finding suggests that pediatricians, in particular,
      must assess more than simply the diagnosis or the cognitive impairment of the
      child with a disability to make informed decisions about the frequency with which
      they should see particular families and whether referral to other services is
      necessary.

PMID- 10071941
TI  - Academic outcome in long-term survivors of pediatric liver transplantation.
AB  - Fifty long-term (3-9 year) survivors of pediatric liver transplantation were
      assessed using IQ, achievement, and school history measures. Forty-seven of these
      children had been evaluated before transplantation on intellectual measures, with
      mean scores for the group found to be in the low average range. At follow-up
      evaluation, the scores remained in the low average range on all intellectual
      measures; performance on academic tests was also within the low average range.
      Thirteen children (26%) were classified as having learning problems based on
      discrepancies between intellectual and academic function, but only five of them
      (38%) had received special education services. Nine of the children (18%) had IQ
      scores less than 70. Academic outcome did not relate to diagnosis, time between
      diagnosis and transplantation, age at time of transplantation, or average levels
      of cyclosporin A. Careful assessment and appropriate special education services
      are indicated to optimize the educational outcome of children who survive liver
      transplantation.

PMID- 10071942
TI  - The Physician Belief Scale and psychosocial problems in children: a report from
      the Pediatric Research in Office Settings and the Ambulatory Sentinel Practice
      Network.
AB  - Clinicians' management of children with psychosocial problems may vary with their
      attitudes and beliefs. However, we lack sound instruments to assess these
      factors. This study examined the psychometric properties of the Physician Belief
      Scale (PBS). A modified version of the PBS was sent to clinicians who
      participated in two primary care research networks. Using factor analysis, we
      reduced the PBS to 14 items and 2 subscales. Cronbach's alpha values were high.
      Female clinicians, those using DSM-IV, and those having completed training
      earlier rated themselves as more psychosocially oriented. Identification and
      treatment of psychosocial problems were significantly related to scores on the
      Belief and Feeling subscale. The PBS provided only a modest amount of information
      regarding primary care practices. It is not clear if these limitations are
      attributable to the instrument or the many other barriers to effective
      psychosocial care.

PMID- 10071943
TI  - Case studies: psychological test findings for two children with X-linked
      adrenoleukodystrophy.
AB  - Psychological evaluations were performed on two children with X-linked
      adrenoleukodystrophy. Case histories are presented that describe the natural
      history of the disorder and its symptom patterns, some of which mirror
      psychiatric disorders of childhood. Psychological evaluation test scores for both
      boys are displayed in a table, and commonalities and differences are discussed.
      Findings are reviewed to expedite the referral process for a definitive
      diagnosis. Guidelines are provided regarding the differential diagnosis of
      adrenoleukodystrophy and other neurodegenerative disorders of childhood from the
      more prevalent disorders of behavior and learning that may present in a
      developmental clinic. Finally, recommendations for psychological interventions
      with the affected child and family members are provided.

PMID- 10071944
TI  - The debate on bilingual education.

PMID- 10071945
TI  - Selective mutism.

PMID- 10071946
TI  - Population-based data and the development of individual children: the case of low
      to moderate lead levels and intelligence.
AB  - This essay is an exploration of the problem of applying research results based on
      large numbers to the individual child and the child's development. The main
      argument of the article is that the results of population-based studies are not
      directly relevant to individuals and that attempts to apply findings to
      individual children are often based on misunderstandings about measurement,
      statistics, and the processes of development. Although research into the
      relationship of elevated lead levels and cognitive development serves as a
      specific context for exploring these general issues, the issues are germane to
      many areas of development and many potential influences. The goal of the article
      is to provide an explicit discussion of scientific issues presented to members of
      the public and potential sources of confusion.

PMID- 10071947
TI  - Recent progress in the neurology of learning: memory molecules in the developing
      brain.
AB  - Memory, the ability to store and retrieve information, is essential for learning
      in children. Modern neurobiology research is revealing some of the fundamental
      steps that encode memories within networks of neuronal synaptic connections in
      the brain. Somewhat different networks store verbal declarative memories and
      habit or procedural memories. Several biochemical steps convert short-term
      memories into permanent memories. These changes include activation of
      neurotransmitter and growth factor receptors, intracellular protein kinases, and
      nuclear transcription factors that stimulate gene expression of memory proteins.
      The proteins strengthen synaptic connections and stabilize long-term memories.
      Genetic defects in those pathways appear to be responsible for several human
      retardation and learning disability syndromes, including Coffin-Lowry syndrome
      and neurofibromatosis.

PMID- 10071948
TI  - Presidential address: the promise of collaborative care.

PMID- 10071949
TI  - The hyperphenylalaninemias (hyperphes), including phenylketonuria (PKU), are
      genetic disorders of phenylalanine (Phe) hydroxylation.

PMID- 10071950
TI  - Children with PDD need to be evaluated by clinical geneticists. Pervasive
      developmental disorder.

PMID- 10071951
TI  - Development of TGF-beta resistance during malignant progression.
AB  - Transforming growth factor-beta (TGF-beta) is the prototypical multifunctional
      cytokine, participating in the regulation of vital cellular activities such as
      proliferation and differentiation as well as a number of basic physiological
      functions. The effects of TGF-beta are critically dependent on the expression and
      distribution of a family of TGF-beta receptors, the TGF-beta types I, II, and
      III. It is now known that a wide variety of human pathology can be caused by
      aberrant expression and function of these receptors. The coding sequence of the
      type II receptor (RII) appears to render it uniquely susceptible to DNA
      replication errors in the course of normal cell division. By virtue of its key
      role in the regulation of cell proliferation, TGF-beta RII should be considered
      as a tumor suppressor gene. High levels of mutation in the TGF-beta RII gene have
      been observed in a wide range of primarily epithelial malignancies, including
      colon and gastric cancer. It appears likely that mutation of the TGF-beta RII
      gene may be a very critical step in the pathway of carcinogenesis.

PMID- 10071952
TI  - Purification and characterization of Moran 20K from Morus alba.
AB  - A new glycoprotein was purified from the aqueous methanolic extract of the root
      bark of Morus alba which has been used as a component of antidiabetic remedy in
      Oriental Medicine. SDS-PAGE result shows that the molecular weight of the
      glycoprotein was approximately 20 kDa. This new glycoprotein was named as Moran
      20K. The protein lowered blood glucose level in streptozotocin-induced
      hyperglycemic mice model and it also increased the glucose transport in cultured
      epididymis fat cells. The amino acid composition of the protein was analyzed, and
      the protein contained above 20% serine and cysteine such as insulin. The actual
      molecular weight of the protein was determined as 21,858 Da by MALDI-TOF mass
      spectroscopy.

PMID- 10071953
TI  - The kinetic characteristics of K228G mutant horse liver alcohol dehydrogenase.
AB  - The kinetic constants and the reaction mechanism of the K228G mutant horse liver
      alcohol dehydrogenase isoenzyme E (HLADH-E) were compared to the wild-type
      enzyme. All the Km and Ki constants of the mutant enzyme for NAD+, ethanol,
      acetaldehyde and NADH were larger than those of the wild-type enzyme. The
      dissociation constants for the NADH and NAD+ (Kiq and Kia) were greatly increased
      by 130- and 460-fold, respectively. The product inhibition patterns suggested
      that the reaction mechanism of the mutant enzyme was changed to Random Bi Bi.
      These results could attribute to the increase in the dissociation rate of
      coenzyme with the substitution at Lys-228 residue.

PMID- 10071954
TI  - Inhibition of cyclooxygenase/lipoxygenase from human platelets by
      polyhydroxylated/methoxylated flavonoids isolated from medicinal plants.
AB  - Various flavonoid derivatives were previously reported to possess the inhibitory
      activity on cyclooxygenase/lipoxygenase. And these properties of flavonoids might
      contribute to their anti-inflammatory activity in vivo. In this study, several
      polyhydroxylated/methoxylated flavonoid derivatives such as oroxylin A, wogonin,
      skullcapflavone II, tectorigenin and iristectorigenin A were isolated from the
      medicinal plants. These compounds were evaluated for their inhibitory effects on
      cyclooxygenase/lipoxygenase from the homogenate of human platelets in vitro. It
      was found that isoflavones including daidzein and tectorigenin possessed the
      inhibitory activity on cyclooxygenase, although the potency of inhibition was far
      less than that of indomethacin. In addition, oroxylin A, baicalein and wogonin
      inhibited 12-lipoxygenase activity without affecting cyclooxygenase, which
      suggested that 5,6,7- or 5,7,8-trisubstitutions of A-ring of flavone gave
      favorable results. The IC50 values of oroxylin A and NDGA against 12-lipoxygenase
      were found to be 100 and 1.5 microM, respectively.

PMID- 10071955
TI  - Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the
      antibacterial activity against methicillin-resistant Staphylococcus aureus and
      the DNA gyrase-inhibitory activity.
AB  - Psammaplin A, a natural bromotyrosine derivative from an associated form of two
      sponges (Poecillastra sp. and Jaspis sp.) was found to possess the antimicrobial
      effect on the Gram-positive bacteria, especially on methicillin-resistant
      Staphylococcus aureus (MRSA). The minimal inhibitory concentration of psammaplin
      A against twenty one MRSAs ranged from 0.781 to 6.25 microg/ml, while that of
      ciprofloxacin was 0.391-3.125 microg/ml. Psammaplin A could not bind to
      penicillin binding protein, but inhibited the DNA synthesis and the DNA gyrase
      activity with the respective 50% (DNA synthesis) and 100% (DNA gyrase) inhibitory
      concentration 2.83 and 100 microg/ml. These results indicate that psammaplin A
      has a considerable antibacterial activity, although restricted to a somewhat
      narrow range of bacteria, probably by inhibiting DNA gyrase.

PMID- 10071956
TI  - Metabolism of liriodendrin and syringin by human intestinal bacteria and their
      relation to in vitro cytotoxicity.
AB  - When liriodendrin or syringin was incubated for 24 h with human intestinal
      bacteria, two metabolites, (+)-syringaresinol-beta-D-glucopyranoside and (+)
      syringaresinol, from liriodendrin and one metabolite, synapyl alcohol, from
      syringin were produced. The metabolic time course of liriodendrin was as follows:
      at early time, liriodendrin was converted to (+)-syringaresinol-beta-D
      glucopyranoside, and then (+)-syringaresinol. The in vitro cytotoxicities of
      these metabolites, (+)-syringaresinol and synapyl alcohol, were superior to those
      of liriodendrin and syringin.

PMID- 10071957
TI  - Effects of placing micro-implants of melatonin in striatum on oxidative stress
      and neuronal damage mediated by N-methyl-D-aspartate (NMDA) and non-NMDA
      receptors.
AB  - Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors
      has been reported to induce excitatoxicity which can be characterized by neuronal
      damage and formation of reactive oxygen free radicals. Neuroprotective effect of
      melatonin against KA-induced excitotoxicity have been documented in vitro and in
      vivo. It is, however, not clear whether melatonin is also neuroprotective against
      excitotoxicity mediated by NMDA receptors. In the present work, we tested the in
      vivo protective effects of striatally infused melatonin against the oxidative
      stress and neuronal damage induced by the injection of KA and NMDA receptors into
      the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel
      cannule with melatonin fused inside the tip were placed bilaterally in the rat
      brain one week prior to intrastriatal injection of glutamate receptor subtype
      agonists. Melatonin showed protective effects against the elevation of lipid
      peroxidation induced by either KA or NMDA and recovered Cu,Zn-superoxide
      dismutase activities reduced by both KA and NMDA into the control level.
      Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal
      damage assessed by the determination of choline acetyltransferase activity in
      striatal homogenages and by microscopic observation of rat brain section stained
      with cresyl violet. The protective effects of melatonin are comparable to those
      of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively.
      It is suggested that melatonin could protect against striatal oxidative damages
      mediated by glutamate receptors, both non-NMDA and NMDA receptors.

PMID- 10071958
TI  - Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine
      derivatives.
AB  - Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti
      inflammatory efficacy and their effects on gastric irritation were evaluated.
      Among the three compounds, 39 exhibited the most potent analgesic action, but the
      effect was weaker than that of piroxicam. Nonetheless, the compound showed 4
      times more potent analgesic action with less gastric damage than did ibuprofen.
      These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.

PMID- 10071959
TI  - Nitric oxide synthase inhibitor decreases NMDA-induced elevations of
      extracellular glutamate and intracellular Ca2+ levels via a cGMP-independent
      mechanism in cerebellar granule neurons.
AB  - These studies were designed to examine the differential effect of nitric oxide
      (NO) and cGMP on glutamate neurotransmission. In primary cultures of rat
      cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate
      (NMDA) stimulates the elevation of intracellular calcium concentration ([Ca2+]i),
      the release of glutamate, the synthesis of NO and an increase of cGMP. Although
      NO has been shown to stimulate guanylyl cyclase, it is unclear yet whether NO
      alters the NMDA-induced glutamate release and [Ca2+]i elevation. We showed that
      the NO synthase inhibitor, N(G)-monomethyl-L-arginine (NMMA), partially prevented
      the NMDA-induced release of glutamate and elevation of [Ca2+]i and completely
      blocked the elevation of cGMP. These effects of NO on glutamate release and
      [Ca2+]i elevation were unlikely to be secondary to cGMP as the cGMP analogue,
      dibutyryl cGMP (dBcGMP), did not suppress the effects of NMDA. Rather, dBcGMP
      slightly augmented the NMDA-induced elevation of [Ca2+]i with no change in the
      basal level of glutamate or [Ca2+]i. The extracellular NO scavenger
      hydroxocobalamine prevented the NMDA-induced release of glutamate providing
      indirect evidence that the effect of NO may act on the NMDA receptor. These
      results suggest that low concentration of NO has a role in maintaining the NMDA
      receptor activation in a cGMP-independent manner.

PMID- 10071960
TI  - Inhibition of lipopolysaccharide-induced inducible nitric oxide (iNOS) mRNA
      expression and nitric oxide production by higenamine in murine peritoneal
      macrophages.
AB  - Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been
      implicated as a mediator of inflammation in rheumatic and autoimmune diseases.
      The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS
      by bacterial lipopolysaccharide (LPS) were examined in murine peritoneal
      macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by
      higenamine which at 0.01 mM, decreased nitrite/nitrate levels by 48.7+/-4.4%.
      This was comparable to the inhibition of LPS-induced nitrite/nitrate production
      by tetrandrin (49.51+/-2.02%) at the same concentration. Northern and Western
      blot analysis of iNOS expression demonstrated that iNOS expression was
      significantly attenuated following co-incubation of peritoneal macrophages with
      LPS (10 microg/ml; 18 hrs) and higenamine (0.001, 0.01 mM; 18 hrs). These results
      suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine
      peritoneal macrophages. The clinical implications of these findings remain to be
      established.

PMID- 10071961
TI  - Biotransformation of theophylline in cirrhotic rats induced by biliary
      obstruction.
AB  - The object of this work was to study the pharmacokinetic differences and the
      cause of these differences in cirrhotic rats induced by biliary obstruction when
      aminophylline (8 mg/kg as theophylline, i.v.) was administered. The
      concentrations of theophylline and its major metabolite (1,3-dimethyluric acid)
      in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric
      acid from theophylline in microsomes and the changes in the activity of drug
      metabolizing enzymes, which are suggested to be involved in theophylline
      metabolism, were determined. In cirrhotic rats, the systemic clearance of
      theophylline was reduced to 30% of the control value while AUC (area under the
      plasma concentration-time curve) and (t1/2)beta were increased 1.3 fold and 3.5
      fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30%
      of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat
      liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N
      demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related),
      which were reported to be related with theophylline metabolism, were decreased to
      67%, 53%, and 76% that of normal rat liver, respectively. From the results, it
      can be concluded that in cirrhotic rats induced by biliary obstruction, the total
      body clearance of theophylline is markedly reduced and it may be due to decreased
      activity of drug metabolizing enzymes in liver.

PMID- 10071962
TI  - Synthesis of 6-exomethylenepenams as beta-lactamase inhibitors.
AB  - The 6,6-dibromopenam (6) was treated with CH3MgBr and carbaldehyde 5 to afford
      the hydroxy compound 7, which was reacted with acetic anhydride to give acetoxy
      compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6
      exomethylenepenams, E-isomer 10 and Z-isomer 9, which was oxidized to sulfone 11
      by m-CPBA. The p-methoxybenzyl compounds were deprotected by AlCl3 and
      neutralized to give the sodium salts 12, 13 and 14.

PMID- 10071963
TI  - Acetophenones from the roots of Cynanchum wilfordii H(EMSLEY)
AB  - Two acetophenones, cynandione A (1) and cynanchone A (2), were isolated from the
      roots of Cynanchum wilfordii. Their structures were identified by comparison of
      their physicochemical and spectral data with reported values.

PMID- 10071964
TI  - Inhibitory constituents against HIV-1 protease from Agastache rugosa.
AB  - Two diterpenoid compounds, agastanol (1) and agastaquinone (2), were isolated
      from the roots of Agastache rugosa (Labiatae). Compound 1 and 2 showed
      significant inhibitory effects against human immunodeficiency virus type 1 (HIV
      1) protease activity with IC50 values of 360 and 87 microM, respectively.

PMID- 10071965
TI  - Iridoid compounds from Boschniakia rossica.
AB  - Four iridoid compounds were isolated from methanol extract of Boschniakia rossica
      by repeated column chromatography. Their structures were determined as
      boschnaloside (1), boschnarol (2), bosnarol methylether (3), and 7-deoxy 8
      epiloganic acid (4), respectively. Compound 2, 3, and 4 were isolated for the
      first time from this plant.

PMID- 10071966
TI  - Antioxidative flavonoids from the leaves of Morus alba.
AB  - Nine flavonoids (1-9) were isolated from the leaves of Morus alba (Moraceae). The
      structures of compounds were determined to be kaempferol-3-O-beta-D
      glucopyranoside (astragalin, 1) kaempferol-3-O-(6"-O-acetyl)-beta-D
      glucopyranoside (2), quercetin-3-O-(6"-O-acetyl)-beta-D-glucopyranoside (3),
      quercetin-3-O-beta-D-glucopyranoside (4), kaempferol-3-O-alpha-L-rhamnopyranosyl
      (1-->6)-beta-D-glucopyranoside (5), quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)
      beta-D-glucopyranoside (rutin, 6), quercetin-3-O-beta-D-glucopyranosyl-(1-->6)
      beta-D-glucopyranoside (7), quercetin-3,7-di-O-beta-D-glucopyranoside (8) and
      quercetin (9) on the basis of spectroscopic and chemical studies. Compounds 7 and
      9 exhibited significant radical scavenging effect on 1,1-diphenyl-2
      picrylhydrazyl radical.

PMID- 10071967
TI  - Advanced method for determination of omeprazole in plasma by HPLC.
AB  - An advanced and sensitive high-performance liquid chromatographic (HPLC) method
      for determination of omeprazole in human plasma has been developed. After
      omeprazole was extracted from plasma with diethylether, the organic phase was
      transferred to another tube and trapped back with 0.1 N NaOH solution. The
      alkaline aqueous layer was injected into a reversed-phase C8 column. Lansoprazole
      was used as an internal standard. The mobile phase consisted of 30% of
      acetonitrile and 70% of 0.2 M KH2P04, pH 7.0. Recoveries of the analytes and
      internal standard were >75.48%. The coefficients of variation of intra- and inter
      day assay were <5.78 and 4.59% for plasma samples. The detection limit in plasma
      was 2 ng/ml. The clinical applicability of this assay method was evaluated by
      determining plasma concentration-time courses of the respective analytes in 24
      healthy volunteers after oral administration 40 mg of omeprazole. The present
      assay is considered to be simple, accurate, economical and suitable for the study
      of the kinetic disposition of omeprazole in the body.

PMID- 10071968
TI  - Current initial therapy of stage III and IV ovarian cancer: challenges for
      managed care.
AB  - Patients with advanced ovarian cancer (International Federation of Gynecology and
      Obstetrics stage III or stage IV) have improved their long-term prognosis, but
      the majority will still die of their disease. The current standard therapy, which
      involves aggressive cytoreductive surgery (removal of all visible tumor) followed
      by platinum/paclitaxel chemotherapy, has increased 5-year survival rates
      considerably over the last three decades. The choice of treatment for patients
      with stage III or IV disease in the managed care setting must consider survival
      rates, patient quality of life, and cost-effectiveness. Two chemotherapy
      combinations, cisplatin/paclitaxel and carboplatin/paclitaxel, appear comparable
      in efficacy in advanced disease, but are currently being investigated in clinical
      trials to compare side effects, quality-of-life parameters, and cost
      effectiveness. The results of these trials may determine which chemotherapy
      combination becomes the standard of care for first-line treatment. Managed care
      organizations and patients can also benefit from a multidisciplinary approach to
      cancer care that includes additional support, such as risk assessment programs,
      the use of specialists (gynecologic oncologists), and psychosocial counseling. As
      the search for more effective agents and other therapeutic modalities continues,
      the focus of future research may be to find specific biomarkers of ovarian
      cancer, which will help detect disease at its earliest stages.

PMID- 10071969
TI  - Treatment of refractory and recurrent ovarian cancer.
AB  - Patients with recurrent ovarian cancer can be divided into two groups: those who
      have recurrence more than 6 months after primary therapy with paclitaxel/platinum
      (ie, platinum-sensitive) and those with tumor progression or recurrence within 6
      months of primary therapy (ie, platinum-resistant). In patients with platinum
      sensitive tumors and good performance status, re-treatment with
      paclitaxel/platinum combination therapy is usually the most appropriate choice.
      For patients with minimum residual disease, the greatest promise for long-term
      disease-free survival is associated with intensive intraperitoneal therapy with
      combinations of cisplatin and intravenous/intraperitoneal paclitaxel.
      Alternatively, patients with platinum-sensitive disease can receive intravenous
      carboplatin or paclitaxel. Patients with platinum-resistant ovarian cancer can
      benefit from single-agent therapy with altretamine, topotecan, oral etoposide,
      ifosfamide, liposomal doxorubicin, or other standard or investigational regimens.
      (Of these drugs, only altretamine and topotecan are approved by the US Food and
      Drug Administration for persistent or recurrent ovarian cancer.) Since the
      response rates achieved with these drugs are similar, patient convenience, side
      effects, and cost may play a significant role in drug selection.

PMID- 10071970
TI  - Management of side effects in patients with recurrent ovarian cancer.
AB  - As with many other aspects of health care delivery in the United States, the
      entrenchment of managed care practices has significantly affected the management
      of patients with advanced ovarian cancer. Nurses continue to play a vital role in
      the delivery of health care in this venue, serving as the primary conduit between
      patients, physicians, and payers. One important aspect of the nurse's interaction
      within this system is in the management of adverse effects, since prompt
      management of these effects can minimize discomfort and inconvenience to the
      patient, save time for the physician, and reduce overall health care costs.
      Physician-directed management algorithms facilitate prompt intervention in a
      variety of situations, by providing a proven framework through which the
      clinician can proceed. A series of representative algorithms are presented, all
      of which may be implemented as provided or customized to fit the needs of any
      individual practice.

PMID- 10071971
TI  - Quality of life issues in the management of ovarian cancer.
AB  - In patients with ovarian cancer, quality of life is defined by the severity of
      the disease. In early stage disease, patients focus on the long-term effects of
      therapy, whereas in late-stage disease, symptom management is paramount. The
      chemotherapeutic agents used to combat ovarian cancer have a wide range of
      adverse effects, the management of which is key to ensuring a patient's quality
      of life. Patient-specific considerations are also important in maintaining
      quality of life. However, patient preferences are hard to define and harder to
      predict, so that it is important to assess each patient individually. A large
      number of assessment tools have been developed, but many are too cumbersome to
      administer regularly and provide information that cannot be incorporated into
      patient care plans. The Functional Assessment of Cancer Therapy questionnaire for
      ovarian cancer (FACT-O) is a notable exception to this group. The FACT-O is a
      short questionnaire grouped by logical categories that can be completed by most
      patients without assistance within 5 minutes. Furthermore, the FACT-O allows
      patients to weight each category of questions based on the categories' perceived
      importance to the quality of the patients' lives. These two factors allow the
      FACT-O to be used to institute management decisions on the level of both the
      individual patient and the institution.

PMID- 10071972
TI  - The effect of reimbursement policies on the management of Medicare patients with
      refractory ovarian cancer.
AB  - Ovarian cancer patients who are covered by Medicare are faced with therapeutic
      decisions that require consideration of out-of-pocket costs for oral anticancer
      agents and complete reimbursement for more expensive intravenous and often more
      toxic medications. The response rates for oral agents such as altretamine or
      etoposide are similar to those for intravenous paclitaxel or topotecan (14% to
      26%), but the economic considerations differ markedly. Under current legislation,
      Medicare will completely cover the costs for the two intravenous outpatient
      chemotherapy regimens, but does not provide any financial support for oral
      regimens that do not have associated injectable formulations. This is a matter of
      concern for patients, as 89% prefer oral therapies. We compared the out-of-pocket
      costs and costs to the Medicare system of oral and intravenous agents used for
      refractory ovarian cancer, using published phase II and phase III data. The total
      cost of treatment was $18,635 for topotecan, $15,767 for paclitaxel, $7,721 for
      etoposide, and $4,477 for altretamine. Conversely, out-of-pocket costs for
      Medicare patients without Medigap coverage were highest for altretamine, at the
      full cost of $4,477, whereas Medicare covered all but $83 for topotecan, $37 for
      paclitaxel, and $66 for etoposide. Current Medicare reimbursement policies may
      affect patient options for cancer care. These policies are changing and should
      continue to change as Medicare adopts more managed care strategies.

PMID- 10071973
TI  - Implementation of disease management guidelines in patients with advanced ovarian
      cancer.
AB  - Individual variability in care practices traditionally has been a strong force in
      oncology practice in the United States. Such variability has necessarily led to
      inconsistencies in resource utilization and quality of care. The concept of
      outcomes management has grown from a recognition of this variability and from a
      desire to both optimize the quality of care and control costs. Disease management
      guidelines are based on the current best evidence and expert opinion. Designed to
      outline appropriate frameworks for care, guidelines reduce variability, minimize
      underutilization and overutilization of resources, provide compliance
      information, and ultimately lead to improved quality of care. Guidelines also can
      form a critical framework for cost estimation. The development of guidelines for
      salvage therapy of ovarian cancer at our institution has led to an excellent
      ability to estimate costs. Institution of these guidelines has led to several
      findings, including the realization that the use of more expensive drugs does not
      necessarily lead to an increase in the overall costs of care. The use of oral
      agents was found to be far less expensive than the use of intravenous agents,
      however. Efficacy analyses are ongoing. The goals for the management of advanced
      ovarian cancer in traditional care and managed care settings are the same: high
      quality care with attention to costs. Such an approach can increase the number of
      patients with this challenging disease who have access to high-quality care.

PMID- 10071974
TI  - Treating advanced ovarian cancer within the health maintenance organization: a
      Kaiser Permanente approach.
AB  - Treatment options for advanced ovarian cancer, a disease that is often terminal,
      are primarily palliative in nature and inherently expensive, presenting a dilemma
      for the managed care organization, whose purpose is to provide high-quality
      health care at a reasonable cost. Kaiser Permanente Northwest, a staff-model
      health maintenance organization providing care to patients in Oregon, Washington,
      and Idaho, has a unique approach to treating advanced ovarian cancer that
      involves the use of flexible evidence-based practice guidelines. These
      guidelines, which consist of state-of-the-art chemotherapy protocols, provide the
      Kaiser physician with the flexibility to treat each patient according to the
      particular stage and potential curability of the tumor. The Kaiser Permanente
      system controls costs by reducing hospital bureaucracy and encouraging treatment
      options that can be administered on an outpatient basis. Kaiser Permanente also
      makes use of multidisciplinary teams in the coordination of care and emphasizes
      the development of and participation in clinical research so that existing
      guidelines can be updated to reflect the best standards of cancer care.

PMID- 10071975
TI  - Managing the care of patients with advanced ovarian cancer.

PMID- 10071976
TI  - Relationship between tumor extracellular fluid exposure to topotecan and tumor
      response in human neuroblastoma xenograft and cell lines.
AB  - PURPOSE: We have reported a 6-fold difference in the topotecan (TPT) lactone
      systemic exposure achieving a complete response in the human neuroblastoma
      xenografts NB-1691 and NB-1643. However, the relationship between tumor
      extracellular fluid (ECF) exposure to TPT and the antitumor activity in xenograft
      and in vitro models has not been established. METHODS: TPT was given i.v. to mice
      bearing NB-1691 and NB-1643 tumors. Prior to dosing, microdialysis probes were
      placed in tumors of mice bearing NB-1691 and NB-1643 tumors. Plasma and tumor ECF
      concentrations of TPT lactone were assayed by high performance liquid
      chromatography. The inhibitory concentration (IC50) was determined for NB-1691
      and NB-1643 cell lines in vitro. RESULTS: The TPT AUC(ECF) values determined for
      NB-1691 (n = 10) and NB-1643 (n = 11) were 7.3 +/- 0.84 and 25.6 +/- 0.76 ng h
      ml(-1), respectively (P < 0.05). TPT tumor ECF penetration in NB-1691 and NB-1643
      was 0.04 +/- 0.04 and 0.15 +/- 0.11 (P < 0.05), respectively. The IC50 values
      recorded after 6 h of TPT exposure daily for 5 consecutive days for NB-1691 and
      NB-1643 were 2.7 +/- 1.1 and 0.53 +/- 0.19 ng/ml, respectively (P < 0.05).
      CONCLUSIONS: NB-1643 was more sensitive in vitro than NB-1691, and at similar
      plasma TPT exposures, NB-1643 had a greater degree of TPT tumor ECF exposure and
      penetration as compared with NB-1691. Potential factors affecting tumor TPT ECF
      disposition include tumor vascularity, capillary permeability, and interstitial
      pressure. The clinical importance of this study is underscored by the need to
      select anticancer agents with a high capacity for tumor penetration and to
      optimize drug administration to increase tumor penetration.

PMID- 10071977
TI  - Aerosol delivery of liposomal all-trans-retinoic acid to the lungs.
AB  - PURPOSE: To optimize the delivery of all-trans-retinoic acid (ATRA) to lung
      tissue, we determined the potential of vehiculating the drug in liposomes (L
      ATRA) and delivering it via aerosol. Liposomes may provide a means to prevent
      local irritation of lung tissue and reduce pulmonary toxicity, prolong
      therapeutic levels and generate high drug concentrations at the tumor sites.
      Cumulatively, this would result in reduced systemic toxicity and enhanced drug
      efficacy. METHODS: Previous studies have shown that liposomes can serve as
      excellent carriers for otherwise poorly soluble ATRA. Delivery of ATRA to the
      lung tissue of mice was accomplished by nebulization of L-ATRA. The liposomes in
      the aerosol were relatively uniform (309 +/- 138 nm), stable, and retained the
      drug well. RESULTS: The drug was effectively delivered at high concentrations (10
      +/- 2 microg/g of tissue) to the lungs of mice and was retained for at least up
      to 96 h after a single exposure to L-ATRA aerosol. No appreciable levels of ATRA
      were detected in the blood or the liver of treated mice. The aerosol-delivered
      ATRA was biologically active as demonstrated by its ability to induce the
      expression of tissue-type transglutaminase. CONCLUSION: Aerosol delivery of L
      ATRA offers an effective way to deliver high levels of ATRA to the lung without
      apparent pulmonary toxic effects.

PMID- 10071978
TI  - Etoposide enhances the lethal effect of radiation on breast cancer cells with
      less damage to mammary gland cells.
AB  - PURPOSE: In the present study, the cytotoxic effects of anticancer drug treatment
      plus radiation on breast cancer and normal mammary gland cells were investigated
      in vitro. METHODS: Breast cancer and adjacent mammary gland tissue was obtained
      from surgically resected specimens from 13 premenopausal female patients, and was
      cultured. Cultured cells were treated with radiation and etoposide, and
      sensitivities were evaluated using an MTT assay. RESULTS: In breast cancer cells,
      radiation alone had a cytotoxic effect. When etoposide was added, synergistic
      effects were achieved which were independent of the radiation dose. The
      cytotoxicity of etoposide against normal gland cells, however, was much the same
      as that against cancer cells, and no synergistic effects were observed in normal
      cells even when radiation was added. CONCLUSIONS: Radiation combined with
      etoposide showed lethal effects against breast cancer cells with less damage to
      normal mammary gland cells.

PMID- 10071979
TI  - Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma.
AB  - Etoposide dosage in patients with liver dysfunction remains controversial. Since
      etoposide has a hepatic component to its clearance (CL) and shows a high degree
      of protein binding, hepatic impairment could affect etoposide disposition.
      However, the empiric recommendation that the dose of etoposide be decreased in
      such patients may reduce systemic exposure and be detrimental to its antitumor
      activity. To address these issues we studied the pharmacokinetics (PK) of
      etoposide in patients with hepatocellular carcinoma (HCC) and underlying
      cirrhosis (n = 17) treated with daily oral etoposide. Unbound etoposide was
      obtained by ultrafiltration. Etoposide concentrations (total and free drug) were
      measured by high-performance liquid chromatography (HPLC) and analyzed by
      noncompartmental equations. The patients had mild or moderate liver dysfunction.
      Albuminemia was in the normal range for all the patients. Creatininemia was
      normal in all but two patients. PK results (mean and range) showed that etoposide
      disposition was unchanged in patients with liver dysfunction. We found slightly
      high etoposide bioavailability [F, 61% (17-95%)] and clearance [CL, 1.1 (0.7
      2.3)l h(-1) m(-2)] resulting in a normal degree of systemic exposure (AUC(oral)
      27 microg h ml(-1)). Normal protein binding [PB 93.2% (84.4-98.1%)] contributed
      to a normal level of exposure to free drug (AUC(f, oral) 1.9 microg h ml(-1)).
      The distribution volume [V(SS) 8.4 (6.1-13.2) l/m2] and the effective half-life
      [t1/2eff, 5.1 (3.0-9.6) h] were normal. Median CL and protein binding did not
      differ in the seven patients with total bilirubin value of > 1.2 mg/dl as
      compared with the ten patients with total bilirubin levels of < or = 1.2 mg/dl
      (1.3 versus 1.01 h(-1) m(-2) and 92.5% versus 93.4%, respectively). In agreement
      with this PK finding, we observed no clinical evidence of increased toxicity in
      patients with hyperbilirubinemia as compared with patients with normal
      bilirubinemia (mean WBC decrease 38% versus 47%). The only case of severe (grade
      4) hematological toxicity was observed in one patient with reduced glomerular
      filtration. Since the pharmacological effects of etoposide correlate with the
      level of systemic exposure to the free drug, our data suggest that no dose
      reduction is needed in patients with HCC. It is even possible to increase the
      dose intensity in patients with favorable PK parameters under appropriate
      hematological and therapeutic drug monitoring.

PMID- 10071980
TI  - Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor
      agent.
AB  - MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-
      oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in
      phase I/II clinical trials, may provide a new approach to cancer therapy based on
      the accumulation in the mitochondria of the cells of certain carcinomas, for
      example, those of the colon, breast and pancreas. To support the development of
      MKT-077 for clinical application as an intravenous (i.v.) therapy, we
      investigated the metabolic fate of [14C]MKT-077 in BDF1 mice as well as the
      distribution of MKT-077 in experimental LS174T tumor-bearing mice using a high
      performance liquid chromatography (HPLC) method. The plasma levels of 14C after
      i.v. administration of [14C]MKT-077 declined in a triphasic manner. In the first
      distribution phase, the levels of 14C decreased with a T1/2 of approximately 5
      min. In the second and terminal phase, the T1/2 of 14C was 2.8-4.6 h and 16.2 h,
      respectively. Cmax (1 min after injection) increased from 0.3 to 1.5 microg/ml
      linearly, but less than proportionately between the doses. The AUC(0-infinity) at
      0.3, 1 and 3 mg/kg were 0.030 +/- 0.002, 0.60 +/- 0.12 and 1.73 +/- 0.25 microg x
      h/ml, respectively. Plasma clearance was approximately 1.8 l/h per kg (at doses
      of 1 and 3 mg/kg). The steady state volume of distribution (6.8 and 25.1 l/kg)
      indicated that MKT-077 distributed as a lipid-soluble molecule. The mean
      residence time (MRT) was 4.1 (at a dose of 1 mg/kg) and 14.1 h (at a dose of 3
      mg/kg). In the first rapid phase (5 min after dosing), 14C radioactivity was
      detected in most of the tissues and organs, most strongly in the kidney cortex,
      and not in the central nervous system and testes. In the terminal phase (24 h
      after dosing), 14C contents increased in the intestinal tract, and in the kidney
      and liver were nearly to the background level. After i.v. bolus administration at
      a dose of 3 mg/kg of [14C]MKT-077, the predominant route of elimination of the
      radioactivity was via the feces, and recoveries of total radioactivity in urine
      and feces corresponded to 33.5% and 61.1%, respectively. More than 60% was
      recovered within 24 h and 95% within 1 week. MKT-077 was primarily excreted in
      unmetabolized form with five unidentified metabolites found in the urine and
      plasma. Intact MKT-077 was retained in the tumor tissue longer than in plasma and
      kidney in LS174T tumor-bearing mice receiving MKT-077 at an i.v. therapeutic dose
      (10 mg/kg). This accumulation decreased very slowly, suggesting that the high
      membrane potentials of tumor cell mitochondria may help retain the drug in
      tumors.

PMID- 10071981
TI  - Mechanism of cytotoxicity of N-[2-(dimethylamino)ethyl] acridine-4-carboxamide
      and of its 7-chloro derivative: the roles of topoisomerases I and II.
AB  - DACA [N-[2-(dimethylamino)ethyl]acridine-4-carboxamide], an acridine derivative
      that is highly active against solid tumours in mice, is currently in clinical
      trial. The ability of DACA to overcome "atypical" (topoisomerase II-mediated)
      multidrug resistance has been hypothesised to stem from its dual topoisomerase
      I/II specificity. We investigated the topoisomerase specificity of DACA and its 7
      chloro derivative (C1-DACA) using camptothecin and amsacrine as control
      compounds. In cell-free assays employing supercoiled plasmid DNA, C1-DACA at 5
      microM induced topoisomerase I-mediated DNA breakage, indicating cleavable
      complex formation (poisoning), and at 10 microM it inhibited relaxation of DNA,
      consistent with suppression (self-inhibition) of poisoning. In this assay, DACA
      provided no evidence of poisoning of this enzyme but inhibited its function at
      concentrations above 10 microM. In DNA cleavage assays utilising purified
      topoisomerase II, DACA induced breakage of supercoiled plasmid DNA at 5 microM
      whereas C1-DACA showed very weak poisoning at 1 microM and inhibition at 5
      microM. Under conditions required for the assay of DNA relaxation, C1-DACA, but
      not DACA, inhibited topoisomerase II action at 5 microM. The actions of DACA and
      C1-DACA could also be distinguished by their ability to form DNA-protein cross
      links in H460 human lung carcinoma cells as measured by precipitation of DNA
      protein complexes with sodium dodecyl sulfate and potassium chloride. Both drugs
      stimulated the formation of complexes at low concentrations but inhibited
      formation at high concentrations. In survival assays with H460 cells, both drugs
      demonstrated biphasic responses with self-inhibition of cytotoxicity at
      intermediate drug concentrations. It was concluded that although both drugs have
      dual topoisomerase I/II specificity, DACA preferentially poisons topoisomerase II
      and C1-DACA preferentially poisons topoisomerase I. In addition, drug-induced
      inhibition of topoisomerase action at higher drug concentrations may mask
      poisoning in the cell-free assays as well as masking cytotoxicity in cultured
      cells. A model in which drug binding occludes topoisomerase-binding sites on the
      DNA can explain this self-inhibition of cytotoxic action.

PMID- 10071982
TI  - Influence of the antacid Maalox on the pharmacokinetics of capecitabine in cancer
      patients.
AB  - PURPOSE: In the present study the possible influence of the antacid Maalox on the
      pharmacokinetics of capecitabine (Xeloda) and its metabolites was investigated in
      cancer patients. METHODS: A total of 12 patients with solid, predominantly
      metastatic tumors of various origin received a single oral dose of 1250 mg/m2 of
      capecitabine (treatment A), a single oral dose of 1250 mg/m2 of capecitabine
      followed immediately by 20 ml of Maalox (treatment B), and a single oral dose of
      1250 mg/m2 of capecitabine followed 2 h later by 20 ml of Maalox (treatment C) in
      an open, randomized, three-way cross over fashion. Serial blood and urine samples
      were collected for up to 24 h after each administration. Unchanged capecitabine
      and its metabolites were analyzed in plasma using liquid chromatography/mass
      spectrometry and in urine using nuclear magnetic resonance spectroscopy. RESULTS:
      Administration of Maalox either concomitantly with capecitabine or delayed by 2 h
      did not influence the time to peak plasma concentrations (Cmax) or the
      elimination half-lives of capecitabine and its metabolites. Unexpectedly,
      moderate increases in the Cmax and AUC0-infinity values obtained for capecitabine
      and 5'-deoxy-5-fluorocytidine were observed when Maalox was given together with
      capecitabine. However, these increases, which ranged between 10% and 31%, were
      not statistically significant (P > 0.05) and are not of clinical significance.
      There was no indication of consistent changes in the plasma concentrations of the
      other metabolites 5'-deoxy-5'-fluorouridine (5'-DFUR), 5-fluorouracil, and alpha
      fluoro-beta-alanine. The Cmax and AUC0-infinity values recorded for these three
      metabolites increased and decreased in a stochastic manner. The magnitude of
      these changes was low (<13%) and not statistically significant. The primary
      statistical analysis of the AUC0-infinity obtained for 5'-DFUR provided a P value
      of 0.4524 and clearly indicated no significant difference between the treatments.
      The addition of Maalox had no influence on the overall urinary recovery or the
      proportion of the dose recovered as capecitabine or its metabolites from urine.
      CONCLUSION: At the dose used in this study, the effect of concomitantly delivered
      Maalox on the extent and rate of gastrointestinal absorption of capecitabine is
      not clinically significant. Therefore, there is no need to adjust the dose or
      timing of capecitabine administration in patients treated with Maalox.

PMID- 10071983
TI  - A limited-sampling strategy for estimation of etoposide pharmacokinetics in
      cancer patients.
AB  - Etoposide (VP16), a widely used anticancer drug, is a topoisomerase II inhibitor.
      A number of studies have highlighted a correlation between hematologic toxicity
      and pharmacokinetic or physiological parameters. Other studies have also
      suggested that the anti-tumor response could be related to the plasma etoposide
      concentration. Therefore, it would seem of interest to individualize VP16 dose
      regimens on the basis of pharmacokinetic parameters. The aim of this study was to
      develop and validate a limited-sampling strategy allowing VP16 pharmacokinetic
      evaluation with minimal disturbance to the patient. A total of 34 patients (54
      kinetics) received VP16 at various dose regimens, with doses ranging between 30
      and 200 mg and infusion times varying between 0.5 and 2 h. The statistical
      characteristics of the pharmacokinetic parameters were assessed from the first
      courses of treatment performed in 23/34 patients; then the following three-sample
      protocol was designed: the end of the infusion and 5 and 24 h after the start of
      the infusion. For validation of the model the main pharmacokinetic parameters
      (clearance, half-lives, volume of distribution) were estimated in the 11
      remaining patients by maximum-likelihood estimation (ML) and by Bayesian
      estimation (BE) using the three sampling times designed. Statistical comparison
      showed a good concordance between ML and BE estimates (the bias for clearance was
      -1.72%). The limited-sampling strategy presented herein can thus be used for
      accurate estimation of VP16 pharmacokinetic parameters.

PMID- 10071984
TI  - Plasma disposition, metabolism and excretion of the experimental antitumour agent
      5,6-dimethylxanthenone-4-acetic acid in the mouse, rat and rabbit.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), an experimental antitumour agent
      currently undergoing phase I clinical trial, has a maximum tolerated dose (MTD)
      in male BDF1 mice of 99 micromol/kg. We have found the male Sprague-Dawley rat
      and the New Zealand White rabbit to have greater tolerance to DMXAA, with MTDs
      being 990 and 330 micromol/kg, respectively. To investigate the causes of this
      difference, we measured plasma and urine DMXAA concentrations by high-performance
      liquid chromatography (HPLC) after single i.v. bolus injections of 99 and 990
      micromol/kg in the rat and following a bolus dose of 99 micromol/kg and a 10-min
      infusion of 330 micromol/kg in the rabbit. Following administration of DMXAA at
      the MTD in the mouse, rat and rabbit the maximal concentrations were 600, 2,200
      and 1,708 microM, respectively, whereas areas under the concentration-time curves
      were 2,400, 19,000 and 2,400 microMh, respectively, for unchanged DMXAA. Data
      obtained for mice and rabbits were satisfactorily fitted to a two-compartment
      model with Michaelis-Menten kinetics. DMXAA was highly bound to plasma proteins,
      with the highest degree of binding being found in the rabbit. A small proportion
      of the total dose (7.8%, 0.6% and 12.4%, respectively) was excreted unchanged in
      urine over 24 h. This proportion increased (to 11.6%, 3.5% and 72.4%,
      respectively) following alkaline hydrolysis, suggesting the presence of
      glucuronide metabolites. Examination of rat and mouse urine by HPLC revealed the
      presence of two metabolites, which were characterized by mass spectrometry and
      nuclear magnetic resonance to be the acyl glucuronide of DMXAA and 6
      (hydroxymethyl)-5-methylxanthenone-4-acetic acid. Thus, both mice and rats
      metabolise DMXAA by similar pathways. The results demonstrate considerable
      interspecies variations in tolerance to DMXAA that cannot be explained by
      differences in pharmacokinetics.

PMID- 10071985
TI  - Pharmacokinetics of the green tea derivative, EGCG, by the topical route of
      administration in mouse and human skin.
AB  - PURPOSE: (-)-Epigallocatechin gallate (EGCG), the main physiologically active
      polyphenol of green tea, is associated with antitumor and antimutagenic
      activities. The goal of this study was to determine the stability and
      pharmacokinetic parameters of pure EGCG administered topically to human and mouse
      skin. METHODS: EGCG was investigated by measuring drug levels of a 10% ointment
      formulation stored under different conditions over a period of 6 months. To
      determine pharmacokinetic parameters of EGCG following topical application. EGCG
      was applied as 10% EGCG in hydrophilic ointment USP to full-thickness mouse or
      human skin in vitro. The transdermal and intradermal. Penetration of EGCG was
      measured by reverse phase HPLC assays at different time-points. RESULTS: The
      stability of EGCG in hydrophilic ointment USP was dependent on time, temperature
      and the degree of oxidation. For example, 10% EGCG was lost after 2 days at 37
      degrees C, but the same formulation supplemented with 0.1% butylated
      hydroxytoluene (BHT) had significantly longer stability with > or =90% EGCG
      remaining after 130 days at 37 degrees C. Topical application of EGCG in
      hydrophilic ointment USP to human or mouse skin resulted in substantial
      intradermal uptake of up to 1-20% of the applied dose. However, transdermal
      penetration was observed only in mouse skin. CONCLUSION: The present study showed
      that topical application of EGCG in hydrophilic ointment USP achieved high
      concentrations in skin but negligible systemic availability. The drug was
      susceptible to oxidation, but if supplemented with BHT, the hydrophilic ointment
      formulation could potentially be used in clinical trials of skin cancer
      prevention.

PMID- 10071986
TI  - Polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) enhances
      simian virus 40 late gene expression.
AB  - PURPOSE: The polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4
      4) depletes cellular polyamines and inhibits malignant cell growth. We have
      previously shown that BE-4-4-4-4 inhibits nucleosome condensation on supercoiled
      DNA in a cell-free system. Here we sought to determine whether BE-4-4-4-4
      inhibits nucleosome condensation in cells, and whether that effect alters the
      expression of specific genes. METHODS: We used the simian virus 40 (SV-40)
      minichromosome as a model system and studied the expression of the viral late
      genes. It is known that the SV-40 late genes are regulated by the steroid
      receptor elements that, in turn, control gene expression by altering nucleosomal
      organization. RESULTS: We observed a more than six fold increase in SV-40 late
      gene expression in cells pretreated with BE-4-4-4-4 for 18 h. The polyamine
      analog bisethyl norspermine (BE-3-3-3), that does not affect nucleosomal
      condensation in cell free systems and has little effect on chromatin structure in
      cultured human tumor cells, had a negligible effect on SV-40 late gene expression
      under treatment conditions identical to those used with BE-4-4-4-4. CONCLUSION:
      Similar to the findings in the cell-free system, the polyamine analog BE-4-4-4-4
      inhibited nucleosome formation and, thereby, altered the expression of specific
      genes in a cellular system.

PMID- 10071987
TI  - Mechanisms of growth stimulation by suramin in non-small-cell lung cancer cell
      lines.
AB  - PURPOSE: Suramin, a polysulfonated naphthylurea, has been shown to be effective
      in the treatment of several cancers. We have reported that suramin, at dose
      concentrations higher than 140 microM, exerts growth-stimulatory effects in
      several non-small-cell lung cancer (NSCLC) cell lines. The purpose of this study
      was to examine the mechanisms by which suramin exerts this growth-stimulatory
      effect in NSCLC cells. METHODS: NCI-H596 cells were treated with agarose
      immobilized suramin, directly or by addition on cell culture inserts, after which
      growth was determined by [3H]thymidine incorporation. PPADS, a specific
      purinergic receptor antagonist, was used to determine whether suramin acts via
      purinergic receptors. The effect of suramin on epidermal growth factor receptor
      (EGFR) was determined by analyzing receptor phosphorylation and dimerization.
      XAMR 0721, a suramin analogue containing only one of the two polysulfonated arms,
      was also analyzed for its effects on growth and EGFR activation. RESULTS: Agarose
      immobilized suramin stimulated NCI-H596 cell growth, but only when added directly
      to the cells. When the suramin-conjugated beads were added to the cells on cell
      culture inserts, which preclude an interaction with the cell surface but allow
      interaction with the culture medium, there was no effect on proliferation. PPADS
      had no effect on the growth stimulation by suramin; however suramin treatment
      resulted in rapid phosphorylation and dimerization of EGFR. Treatment with XAMR
      0721 did not affect growth or tyrosine phosphorylation and dimerization of EGFR.
      CONCLUSIONS: Suramin need not enter NCI-H596 cells to exert its growth
      stimulatory effect, nor is this effect mediated by an interaction with soluble
      growth factors. Rather, it appears that suramin acts via an interaction with
      EGFR, but not with purinergic receptors.

PMID- 10071988
TI  - Expression of GADD153 in tumor cells and stromal cells from xenografted tumors in
      nude mice treated with cisplatin: correlations with cisplatin-DNA adducts.
AB  - PURPOSE: Cisplatin is a commonly used antineoplastic agent that acts by forming
      adducts with DNA, and causing a response to the cellular injury. One of the
      components of this cellular injury response is the activation of the "growth
      arrest and DNA damage gene" GADD153. The level of GADD153 induction in tumor
      cells has been associated with the degree of cytotoxicity. The pupose of this
      study was to determine whether cisplatin activates GADD153 also in nontumor cells
      and how GADD153 protein levels correlate with cisplatin-DNA adducts in different
      cell types. METHODS: Nude mice with xenografted squamous cell carcinoma were
      treated with cisplatin 10 mg/kg. Tumors were removed at 0 h (untreated controls),
      24 h, and 48 h and immunohistochemically stained for GADD153 protein and
      cisplatin-DNA adducts. The staining reaction was quantitated in tumor cells and
      nonmalignant stromal cells separately, using computerized image analysis.
      RESULTS: The GADD153 level was 4.5 times higher in tumor cells than in stromal
      cells in untreated mice. At 24 h after cisplatin treatment the GADD153 level had
      increased by 50% and 72% in tumor cells and stromal cells, respectively. Analysis
      of the cisplatin-DNA adducts showed a reversed pattern, with six-fold higher
      levels in stromal cells than in tumor cells at 24 h after treatment. By combining
      these data, we estimated that approximately 25-fold more GADD153 per cisplatin
      DNA adduct was induced in tumor cells than in stromal cells. CONCLUSION: Our data
      suggest that different cell types may respond differently to DNA damage caused by
      cisplatin.

PMID- 10071989
TI  - Individualizing beta-adrenergic blocker therapy: patient-specific target-based
      heart rate control.

PMID- 10071990
TI  - The effect of heart rate control on myocardial ischemia among high-risk patients
      after vascular surgery.
AB  - Patients undergoing vascular surgery have a high risk of suffering major
      postoperative cardiac events. Preoperative myocardial ischemia as detected by
      Holter monitoring identifies a high-risk subgroup whose postoperative ischemia,
      similarly detected, seems to herald major cardiac events. In this study, we
      determined whether systematic, patient-specific postoperative heart rate control
      with beta-adrenergic blocker therapy decreases the incidence of postoperative
      ischemia among high-risk vascular surgery patients. A total of 26 of 150 patients
      who underwent elective vascular surgery and were monitored preoperatively by 24-h
      Holter were found to have significant myocardial ischemia as defined by ST
      segment depression. The minimal heart rate at which this ST-segment depression
      occurred was identified (ischemic threshold), and these 26 patients were then
      randomized to receive continuous i.v. beta-blockade with esmolol or placebo plus
      usual medical therapy, aiming to reduce the postoperative heart rate to 20% below
      the ischemic threshold. All patients were monitored by Holter for 48 h
      postoperatively. Postoperative Holter readings were analyzed for the incidence of
      ischemia and for the number of hours during which heart rate was controlled below
      the ischemia threshold. Patients had a median of two episodes of preoperative
      ischemia lasting a median of 30 min (range 1-155 min). A total of 15 patients
      were randomized to receive esmolol, and 11 were randomized to receive placebo.
      The two groups were comparable with respect to clinical characteristics and
      incidence and duration of preoperative ischemia. Ischemia persisted in the
      postoperative period in 8 of 11 placebo patients (73%), but only 5 of 15 esmolol
      patients (33%) (P < 0.05). Of the 15 esmolol patients, 9 had mean heart rates
      below the ischemic threshold, and all 9 had no postoperative ischemia. A total of
      4 of 11 placebo patients had mean heart rates below the ischemic threshold, and 3
      of the 4 had no postoperative ischemia. There were two postoperative cardiac
      events among patients who had postoperative ischemia (one placebo, one esmolol)
      and whose mean heart rates exceeded the ischemic threshold. Our data suggest that
      patient-specific, strict heart rate control aiming for a predefined target based
      on individual preoperative ischemic threshold was associated with a significant
      reduction and frequent elimination of postoperative myocardial ischemia among
      high-risk patients and provide a rationale for a larger trial to examine this
      strategy's effect on cardiac risk. IMPLICATIONS: Patients who undergo peripheral
      vascular surgery often experience transient cardiac complications and/or
      permanent heart damage just after surgery because of inadequate myocardial blood
      flow. In this study, we identified patients at high risk of cardiac complications
      after vascular surgery and showed that if their heart rate was carefully
      controlled for 48 h after surgery, myocardial ischemia, a common marker of heart
      injury, was markedly reduced.

PMID- 10071991
TI  - The effects of in vitro hemodilution with gelatin, hydroxyethyl starch, and
      lactated Ringer's solution on markers of coagulation: an analysis using SONOCLOT.
AB  - Blood-saving strategies have recently been established to avoid allogeneic
      transfusion during surgery or after trauma. This includes an expanding use of
      crystalloids and colloids. These solutions interfere with coagulation systems,
      but quantitative measurements are still lacking. The SONOCLOT (Sienco Company,
      Morrison, CO) analysis (SCT), a viscoelastic test, measures clot formation and
      includes information on the cellular, as well as the plasmatic coagulation,
      system. To quantify hemodilutional effects on in vitro coagulation, we studied
      gelatin (G), hydroxyethyl starch 6% (HES; molecular weight 450,000), and lactated
      Ringer's solution (RL) in 33% and 66% dilutions measuring routines laboratory and
      SCT variables. Hemodilution with RL tended to increase in vitro coagulability.
      Among the tested colloids, G had the least impact on markers of coagulation. G33%
      did not differ significantly from the undiluted control group. HES had the
      largest impact on markers of coagulation compared with G and RL. In conclusion,
      SCT provides a fast and easy to perform bedside test to quantify in vitro
      hemodilution. IMPLICATIONS: The effects of progressive hemodilution on
      coagulation are difficult to measure. SONOCLOT analyses provide an easy to
      perform test with fast information on cellular and plasmatic coagulation
      properties. Among colloids, hydroxyethyl starch has the largest impact on markers
      of coagulation compared with gelatin or lactated Ringer's solution.

PMID- 10071992
TI  - Minimum alveolar anesthetic concentration of volatile anesthetics in normal and
      cardiomyopathic hamsters.
AB  - Minimum alveolar anesthetic concentrations (MAC) values of volatile anesthetics
      in cardiovascular diseases remain unknown. We determined MAC values of volatile
      anesthetics in spontaneously breathing normal and cardiomyopathic hamsters
      exposed to increasing (0.1%-0.3% steps) concentrations of halothane, isoflurane,
      sevoflurane, or desflurane (n = 30 in each group) using the tail-clamp technique.
      MAC values and their 95% confidence interval were calculated using logistic
      regression. In normal hamsters, inspired MAC values were: halothane 1.15% (1.10%
      1.20%), isoflurane 1.62% (1.54%-1.69%), sevoflurane 2.31% (2.22%-2.40%), and
      desflurane 7.48% (7.30%-7.67%). In cardiomyopathic hamsters, they were: halothane
      0.89% (0.83%-0.95%), isoflurane 1.39% (1.30%-1.47%), sevoflurane 2.00% (1.85%
      2.15%), and desflurane 6.97% (6.77%-7.17%). Thus, MAC values of halothane,
      isoflurane, sevoflurane, and desflurane were reduced by 23% (P < 0.05), 14% (P <
      0.05), 13% (P < 0.05), and 7% (P < 0.05), respectively in cardiomyopathic
      hamsters. IMPLICATIONS: Minimum alveolar anesthetic concentrations of volatile
      anesthetics were significantly lower in cardiomyopathic hamsters than in normal
      hamsters.

PMID- 10071993
TI  - Arterial oxygenation during one-lung ventilation: combined versus general
      anesthesia.
AB  - The optimal anesthetic management of patients undergoing thoracotomy for
      pulmonary resection has not been definitely determined. We evaluated whether
      general i.v. anesthesia (propofol-fentanyl) provides superior PaO2 during one
      lung ventilation (OLV) compared with thoracic epidural anesthesia (TEA) with
      supplemental local and general anesthetics. We studied 60 patients who had
      prolonged periods of OLV for elective thoracic surgery for lung cancer and who
      were prospectively randomized into two groups. In 30 patients (GA group),
      fentanyl/propofol/rocuronium anesthesia was used. Another 30 patients (TEA group)
      were anesthetized with propofol/rocuronium/epidural thoracic bupivacaine 0.5%. A
      double-lumen endotracheal tube was inserted, and mechanical ventilation with 100%
      oxygen was used during the entire study. Arterial and venous blood gases were
      recorded before surgery in a lateral position with two-lung ventilation, 15 and
      30 min after OLV (OLV + 15 and OLV + 30, respectively) in all patients. We
      measured PaO2, venous central oxygen tension, arterial and central venous oxygen
      saturation, venous admixture percentage (Qs/Qt%), and arterial and central venous
      oxygen content. The mean values for PaO2 during OLV in the GA group after 15 min
      (175 mm Hg) and 30 min (182 mm Hg) were significantly (P < 0.05) higher compared
      with the TEA group (120 and 118 mm Hg, respectively). Furthermore, Qs/Qt% was
      significantly (P < 0.05) increased in the TEA group during OLV. There were no
      other significant differences. We conclude that using the TEA regimen is
      associated with a lower PaO2 and a larger intrapulmonary shunt during OLV than
      with total i.v. anesthesia alone. IMPLICATIONS: Sixty patients undergoing
      elective lung surgery during a prolonged period of intraoperative one-lung
      ventilation were studied and randomized to receive general i.v. anesthesia or
      general i.v. anesthesia combined with thoracic epidural anesthesia. The arterial
      oxygenation in the first group was better than that in the second group during
      one-lung ventilation.

PMID- 10071995
TI  - The use of nitric oxide for managing catastrophic pulmonary vasoconstriction
      arising from protamine administration.

PMID- 10071994
TI  - Transesophageal echocardiographic detection of gas embolism and cardiac valvular
      dysfunction during laparoscopic nephrectomy.
AB  - We used transesophageal echocardiography (TEE) to monitor venous gas embolism,
      cardiac performance, and the hemodynamic effects of positioning and
      pneumoperitoneum in 16 healthy kidney donors undergoing laparoscopic nephrectomy.
      A four-chamber view was used continuously, except at predetermined intervals,
      when a complete TEE examination for cardiac function was performed. Other
      clinical variables recorded include systolic, diastolic, and mean arterial blood
      pressure; heart rate (HR), pulse oximetric saturations; and end-tidal CO2.
      Baseline valvular incompetence was seen in 13 of the 16 patients when supine and
      asleep. After positioning for surgery and induction of pneumoperitoneum, TEE
      revealed valvular incompetence with regurgitation more pronounced from baseline
      in 15 of the 16 patients. In one patient, during renal vein dissection, gas
      entered the right atrium from the inferior vena cava, worsening tricuspid
      regurgitation. Hemodynamic variables and ejection fraction were tested by using
      repeated-measures analysis of variance for significance (P < 0.05).
      Pneumoperitoneum increased (P < 0.05) systolic blood pressure (from 102.8 +/-
      3.89 to 120.8 +/- 3.88 mm Hg) and HR (from 68.9 +/- 3.19 to 75.6 +/- 2.62).
      Ejection fraction was unchanged. The high incidence of valvular incompetence
      indicates that further studies are needed to assess these effects during
      laparoscopic nephrectomy with cardiac disease. IMPLICATIONS: Laparoscopic surgery
      has gained popularity as a procedure for the removal of donated kidneys. Although
      the insufflation of gas necessary for this relatively simple approach poses a low
      risk of venous air embolism, it may increase the risk of changes in valvular
      competency.

PMID- 10071996
TI  - Discharge criteria and complications after ambulatory surgery.

PMID- 10071997
TI  - Remifentanil administration during monitored anesthesia care: are intermittent
      boluses an effective alternative to a continuous infusion?
AB  - This randomized, double-blind study was designed to evaluate the analgesic
      effectiveness and respiratory stability of remifentanil when administered as
      intermittent bolus injections, a variable-rate infusion, or a combination of a
      constant basal infusion supplemented with intermittent boluses during monitored
      anesthesia care (MAC). Forty-five patients undergoing extracorporeal shock wave
      lithotripsy (ESWL) procedures were randomly assigned to one of the three modes of
      remifentanil administration. All patients received midazolam 2 mg i.v., followed
      by a propofol infusion at 50 microg x kg(-1) x min(-1). Two minutes before
      administering a series of test shock waves: Group I received a remifentanil
      infusion of 0.1 microg x kg(-1) x min(-1), and a saline bolus (5 mL); Group II
      received a saline infusion and a remifentanil bolus (25 microg in 5 mL); and
      Group III received a remifentanil infusion of 0.05 microg x kg(-1) x min(-1), and
      a remifentanil bolus (12.5 microg in 5 mL). The average pain intensity was scored
      on an 11-point scale, with 0 = no pain to 10 = severe pain. During the ESWL
      procedure, pain was treated by increasing the study drug infusion rate by 25%-50%
      and administering 5-mL bolus injections of the study medication in Groups I
      (saline) and II (remifentanil 25 microg). In Group III, intermittent 5-mL boluses
      (remifentanil 12.5 microg) were administered as needed. Patients in Groups II and
      III reported lower pain scores in response to the test shocks. Significantly more
      remifentanil was administered in Group I (379 +/- 207 microg) than in Group II
      (201 +/- 136 microg). However, more interventions were required for the treatment
      of intraoperative pain in the intermittent bolus group (Group II). When
      remifentanil is administered as the analgesic component of a MAC technique, these
      data support the use of intermittent bolus doses (12.5-25 microg) alone or in
      combination with a basal infusion (0.05 microg x kg(-1) x min(-1)) as
      alternatives to a variable-rate continuous infusion. IMPLICATIONS: In this study,
      three different modes of remifentanil administration were used during monitored
      anesthesia care for extracorporeal shock wave lithotripsy procedures. These
      results suggest that using intermittent bolus injections of remifentanil (25
      microg) or a continuous infusion (0.05 microg x kg(-1) x min(-1)) supplemented
      with intermittent bolus (12.5 microg) injections may be more effective than a
      variable-rate infusion of remifentanil during propofol sedation.

PMID- 10071998
TI  - Anesthesia for in vitro fertilization: the addition of fentanyl to 1.5%
      lidocaine.
AB  - Ultrasonically guided transvaginal oocyte retrieval is relatively short procedure
      that is performed on an out-patient basis. The optimal anesthetic technique
      should allow good surgical anesthesia with minimal side effects, a short recovery
      time, and, if possible, a high rate of successful pregnancy. Spinal anesthesia is
      often used in this institution, as well as many others, for this procedure. The
      addition of fentanyl may be effective for both intraoperative and postoperative
      pain relief. We assessed the effect of adding fentanyl to 1.5% lidocaine in women
      undergoing ultrasonically guided oocyte retrieval. Seventy-eight women were
      randomized to receive 45 mg of hyperbaric 1.5% lidocaine with or without 10
      microg of fentanyl. Visual analog scale (VAS) pain scores were lower in the
      operating room (OR) (P < 0.05) and postanesthesia care unit (PACU) (P < 0.0005)
      for the group that received fentanyl. In addition, the amount of narcotic
      required in the PACU was less in the fentanyl group (P < 0.005). There was no
      difference in VAS scores the evening of or 24 h after the procedure. The amount
      of analgesics and narcotics required after discharge was the same for both
      groups. Timed variables, such as time to urination, ambulation, and discharge,
      were the same for both groups of women. The addition of fentanyl to lidocaine for
      transvaginal oocyte retrieval results in a more comfortable patient in the OR and
      PACU. IMPLICATIONS: This study demonstrates that when fentanyl is added to a
      local anesthetic, lidocaine, with spinal anesthesia for egg retrieval procedures,
      patients are more comfortable during the procedure compared with those who
      receive lidocaine alone. In addition, the narcotic requirements of patients are
      less in the postanesthesia care unit.

PMID- 10071999
TI  - An adult system versus a Bain system: comparative ability to deliver minute
      ventilation to an infant lung model with pressure-limited ventilation.
AB  - We compared the efficacy of an adult circle system versus a Bain system to
      deliver minute ventilation (V(E)) to an infant test lung model using pressure
      limited ventilation. To simulate a wide variety of potential infant clinical
      states, V(E) was measured with two compliances: at peak inspiratory pressures
      (PIP) of 20, 30, 40, and 50 cm H2O and at respiratory rates (RR) of 20, 30, 40,
      and 50 breaths/min. Each measurement was made three times, and their average was
      used for analysis. Data were analyzed using the multiple regression technique. In
      both normal and low-compliance lung models, V(E) was nearly identical between
      adult circle and Bain systems (P = 0.67 for normal compliance model, P = 0.89 for
      low-compliance model). V(E) positively correlated with RR (P < 0.001), PIP (P <
      0.001), and lung compliance (P < 0.001). Very high PIP or RR were required to
      deliver V(E) to the low-compliance lung model. The adult circle system is
      equivalent to the Bain system in its ability to ventilate an infant test lung
      over a wide range of RR, PIP, and two compliances during pressure-limited
      ventilation. V(E) is dependent of PIP, RR, and lung compliance. With low
      compliance lungs, both systems require a high PIP. We conclude that both
      anesthetic systems deliver ventilation over a wide range of respiratory variables
      during pressure-limited ventilation in infants. IMPLICATIONS: We obtained results
      from this infant test lung study that indicate that either an adult circle
      breathing system or the Bain system can reliably deliver ventilation over a wide
      range of respiratory variables during pressure-limited ventilation in infants.

PMID- 10072000
TI  - Transcutaneous monitoring of carbon dioxide tension after cardiothoracic surgery
      in infants and children.
AB  - In this prospective investigation, we evaluated the efficacy and accuracy of
      transcutaneous monitoring of CO2 (TC-CO2) in infants and children after
      cardiothoracic surgery. Cardiothoracic surgery patients whose ETCO2 and arterial
      CO2 values did not correlate (gradient > or = 5 mm Hg) during the first
      postoperative hour underwent placement of the TC electrode (30 of 33 patients).
      If the TC-CO2 to arterial difference was > or = 5 mm Hg, the TC-CO2 electrode was
      recalibrated and reapplied on another site. If the discrepancy was still > or =5
      mm Hg, the case was considered a clinical failure and no further data were
      collected (3 of 30 patients). If the arterial to TC gradient was <5 mm Hg, the
      patient was included in the data collection (27 of 30 patients). One to five
      sample sets (TC and arterial CO2) were collected from these patients. Statistical
      analysis included linear regression analysis and Bland-Altman analysis. The
      cohort for the study included 27 patients ranging in age from 2 days to 9 yr and
      in weight from 3.2 to 25 kg. A total of 101 sample sets were analyzed. The mean
      +/- SD absolute difference between the TC-CO2 and arterial CO2 was 1.7 +/- 1.4 mm
      Hg (range 0-9 mm Hg). The TC-CO2 to arterial CO2 difference was 0-2 mm Hg in 82
      of 101 values (81%), 35 mm Hg in 18 of 101 values (18%), and >6 mm Hg in 1 of 101
      values (1%). Linear regression analysis revealed a slope of 0.90, an r value of
      0.9410, and an r2 value of 0.8854 (P < 0.0001). Bland-Altman analysis revealed a
      bias of 0.58 mm Hg with a precision of +/- 2.1 mm Hg when comparing the TC-CO2
      with the arterial CO2. IMPLICATIONS: We conclude that, with certain caveats in
      mind, including the need to correlate the transcutaneous CO2 with an initial
      arterial CO2 value, transcutaneous CO2 monitoring can be used to estimate
      arterial CO2 in most neonates and children after cardiothoracic surgery.

PMID- 10072001
TI  - Protein S deficiency presenting as an acute postoperative arterial thrombosis in
      a four-year-old child.

PMID- 10072002
TI  - The alveolar-arterial difference in oxygen tension increases with temperature
      corrected determination during moderate hypothermia.
AB  - Moderate hypothermia (32-33 degrees C) occurs in anesthetic practice. However,
      intrapulmonary gas exchange and the effect of temperature correction of blood
      gases on oxygen and carbon dioxide exchange have not been investigated in these
      patients. We investigated alveolar-arterial difference in oxygen tension (AaDO2)
      and arterial to end-tidal difference in carbon dioxide (Pa-ETCO2) during
      rewarming of eight ASA physical status I patients from hypothermia of 32 degrees
      C. Anesthesia was maintained with fentanyl/propofol. AaDO2 and Pa-ETCO2 were
      assessed by analyzing arterial blood gases and saturated water vapor pressure,
      uncorrected or corrected to actual body temperature. The respiratory quotient
      (RQ) was measured by calorimetry. After temperature correction of blood gases and
      water vapor pressure, the AaDO2 was significantly higher at 33 and 32 degrees C
      compared with 36 degrees C (56 +/- 13 and 64 +/- 14 vs 39 +/- 10 mm Hg; P < 0.05
      and P < 0.01). The deterioration of pulmonary oxygen exchange was not detected if
      arterial blood gases and water vapor pressure were not corrected. The RQ did not
      change during moderate hypothermia compared with 36 +/-C. The temperature
      corrected Pa-ETCO2 was not affected by hypothermia. We conclude that AaDO2 is
      increased during moderate hypothermia. This is only detected when water vapor
      pressure and arterial blood gases are corrected to actual body temperature.
      IMPLICATIONS: We investigated intrapulmonary oxygen and carbon dioxide exchange
      during moderate hypothermia (32 degrees C) in eight patients. If oxygen, carbon
      dioxide, and water vapor pressure were corrected to actual body temperature, the
      alveolar-arterial oxygen tension difference was increased during hypothermia. The
      carbon dioxide tension difference and the respiratory quotient were unaffected by
      hypothermia.

PMID- 10072003
TI  - The effects of vasopressin on endotoxin-induced attenuation of contractile
      responses in human gastroepiploic arteries in vitro.
AB  - We studied the effects of vasopressin on contraction in normal and endotoxin
      treated human gastroepiploic arterial rings in vitro. In this tissue, vasopressin
      (50-500 pg/mL) produced concentration-dependent, endothelium-independent
      contractions. Vasopressin also potentiated the contraction elicited by 1.0
      micromol/L norepinephrine (NE) in both the presence and absence of endothelium.
      Endotoxin (10 microg/mL) attenuated the 1.0 micromol/L NE-induced contractions,
      and this attenuation was reversed by 300 micromol/L N(G)-nitro-L-arginine-methyl
      ester (L-NAME) and by 300 micromol/L N(G)-nitro-L-arginine (L-NoArg). After 12 h
      endotoxin treatment, the vasopressin-induced contraction was attenuated, and the
      enhancing effect of vasopressin was diminished. However, both before and after
      endotoxin, the enhancement produced by vasopressin was larger than the
      vasopressin-contraction itself. An antagonist of the vasopressin V1 receptor, 1.0
      micromol/L beta-mercapto-[beta,beta-cyclopentamethylenpropionyl1,O-MeTyr2+
      ++,Arg8]-vasopressin, and an antagonist of V1 + V2 receptor receptor, 1.0
      micromol/L des-Gly9-[beta-mercapto-beta,beta-cyclopentamethylenepropionyl1 ,O-Et
      Tyr2,Val,Arg8]-vasopressin, each diminished the vasopressin-induced enhancement
      of the NE contraction. IMPLICATIONS: The results of our study suggest that, in
      addition to its direct vasoconstrictor effect, vasopressin strongly enhances the
      responses to norepinephrine through V1-receptor stimulation and that vasopressin
      could find a role in the management of endotoxin-induced vasodilation.

PMID- 10072004
TI  - Measuring brain tissue oxygenation compared with jugular venous oxygen saturation
      for monitoring cerebral oxygenation after traumatic brain injury.
AB  - Jugular bulb oximetry is the most widely used method of monitoring cerebral
      oxygenation. More recently, measurement of brain tissue oxygenation has been
      reported in head-injured patients. We compared the changes in brain tissue oxygen
      partial pressure (PbO2) with changes in jugular venous oxygen saturation (SjVO2)
      in response to hyperventilation in areas of brain with and without focal
      pathology. Thirteen patients with severe head injuries were studied. A
      multiparameter sensor was inserted into areas of brain with focal pathology in
      five patients and outside areas of focal pathology in eight patients. A
      fiberoptic catheter was inserted into the right jugular bulb. Patients were
      hyperventilated in a stepwise manner from a PaCO2 of approximately 35 mm Hg to a
      PaCO2 of 22 mm Hg. There was no significant change in cerebral perfusion pressure
      or arterial partial pressure of oxygen with hyperventilation. In areas without
      focal pathology, there was a good correlation between changes in SjVO2 and PbO2
      (deltaSjVO2 and deltaPbO2; r2 = 0.69, P < 0.0001). In areas with focal pathology,
      there was no correlation between deltaSjVO, and APbO2 (r2 =0.07, P = 0.23). In
      this study, we demonstrated that measurement of local tissue oxygenation can
      highlight focal differences in regional cerebral oxygenation that are disguised
      when measuring SjVO2. Thus, monitoring of PbO2 is a useful addition to multimodal
      monitoring of patients with traumatic head injury. IMPLICATIONS: Brain
      oxygenation is currently monitored by using jugular bulb oximetry, which attracts
      a number of potential artifacts and may not reflect regional changes in
      oxygenation. We compared this method with measurement of brain tissue oxygenation
      using a multiparameter sensor inserted into brain tissue. The brain tissue
      monitor seemed to reflect regional brain oxygenation better than jugular bulb
      oximetry.

PMID- 10072005
TI  - Continuous measurement of cerebral oxygenation by near infrared spectroscopy
      during induction of anesthesia.
AB  - Near infrared spectroscopy (NIRS) measures tissue oxygenation continuously at the
      bedside. Major disturbances of cerebral oxygenation can be detected by using
      NIRS, but the ability to observe smaller changes is poorly documented. Although
      anesthetics generally depress cerebral metabolism and enhance oxygen delivery,
      the administration of etomidate has been associated with cerebral desaturation.
      We used this difference to study the ability of NIRS to detect the small changes
      associated with the onset of anesthesia. Thirty-six healthy patients were
      randomly allocated to have anesthesia induced with either etomidate, propofol, or
      thiopental. We found that there was a temporal association between the onset of
      anesthesia and NIRS-derived indices of cerebral oxygenation. Etomidate was
      associated with a decrease in cerebral oxygenation, whereas propofol and
      thiopental were associated with an increase in cerebral oxygenation. We conclude
      that NIRS is capable of detecting the small changes in cerebral oxygenation
      associated with the induction of general anesthesia and shows promise as a
      bedside investigational tool for the noninvasive assessment of cerebral
      oxygenation. IMPLICATIONS: We conclude that near infrared spectroscopy is capable
      of detecting the small changes in cerebral oxygenation associated with the
      induction of general anesthesia and shows promise as a bedside investigational
      tool for the noninvasive assessment of cerebral oxygenation.

PMID- 10072006
TI  - The influence of anesthetic choice, PaCO2, and other factors on osmotic blood
      brain barrier disruption in rats with brain tumor xenografts.
AB  - Increasing the delivery of therapeutic drugs to the brain improves outcome for
      patients with brain tumors. Osmotic opening of the blood-brain barrier (BBB) can
      markedly increase drug delivery, but achieving consistent, good quality BBB
      disruption (BBBD) is essential. We evaluated four experiments compared with our
      standard isoflurane/O2 protocol to improve the quality and consistency of BBBD
      and drug delivery to brain tumor and normal brain in a rat model. Success of BBBD
      was assessed qualitatively with the large molecular weight marker Evans blue
      albumin and quantitatively by measuring delivery of the low molecular weight
      marker [3H]-methotrexate. With isoflurane/O2 anesthesia, the effects of two BBBD
      drugs of different osmolalities were evaluated at two different infusion rates
      and infusion durations. Arabinose was superior to saline (P = 0.006) in obtaining
      consistent Evans blue staining in 16 of 24 animals, and it significantly
      increased [3H]-methotrexate delivery compared with saline in the tumor (0.388 +/-
      0.03 vs 0.135 +/-0.04; P = 0.0001), brain around the tumor (0.269 +/- 0.03 vs
      0.035 +/- 0.03; P = 0.0001), brain distant to the tumor (0.445 +/- 0.05 vs 0.034
      +/- 0.07; P = 0.001), and opposite hemisphere (0.024 +/- 0.00 vs 0.016 +/- 0.00;
      P = 0.0452). Forty seconds was better than 30 s (P = 0.0372) for drug delivery to
      the tumor. Under isoflurane/O2 anesthesia (n = 30), maintaining hypocarbia was
      better than hypercarbia (P = 0.025) for attaining good BBBD. A propofol/ N2O
      regimen was compared with the isoflurane/O2 regimen, altering blood pressure,
      heart rate, and PaCO2 as covariates (n = 48). Propofol/N2O was superior to
      isoflurane/O2 by both qualitative and quantitative measures (P < 0.0001).
      Neurotoxicity and neuropathology with the propofol/N2O regimen was evaluated, and
      none was found. These data support the use of propofol/N2O along with maintaining
      hypocarbia to optimize BBBD in animals with tumors. IMPLICATIONS: Propofol/N2O
      anesthesia may be better than isoflurane/O2 for optimizing osmotic blood-brain
      barrier disruption for delivery of chemotherapeutic drugs to brain tumor and
      normal brain.

PMID- 10072007
TI  - A comparison of myogenic motor evoked responses to electrical and magnetic
      transcranial stimulation during nitrous oxide/opioid anesthesia.
AB  - Transcranial motor evoked potentials (tc-MEPs) are used to monitor spinal cord
      integrity intraoperatively. We compared myogenic motor evoked responses with
      electrical and magnetic transcranial stimuli during nitrous oxide/opioid
      anesthesia. In 11 patients undergoing spinal surgery, anesthesia was induced with
      i.v. etomidate 0.3 mg/kg and sufentanil 1.5 microg/kg and was maintained with
      sufentanil 0.5 microg x kg(-1) x h(-1) and N2O 50% in oxygen. Muscle relaxation
      was kept at 25% of control with i.v. vecuronium. Electrical stimulation was
      accomplished with a transcranial stimulator set at maximal output (1200 V).
      Magnetic transcranial stimulation was accomplished with a transcranial stimulator
      set at maximal output (2 T). Just before skin incision, triplicate responses to
      single stimuli with both modes of cortical stimulation were randomly recorded
      from the tibialis anterior muscles. Amplitudes and latencies were compared using
      the Wilcoxon signed rank test. Bilateral tc-MEP responses were obtained in every
      patient with electrical stimulation. Magnetic stimulation evoked only unilateral
      responses in two patients. With electrical stimulation, the median tc-MEP
      amplitude was 401 microV (range 145-1145 microV), and latency was 32.8 +/- 2.3
      ms. With magnetic stimulation, the tc-MEP amplitude was 287 microV (range 64-506
      microV) (P < 0.05), and the latency was 34.7 +/- 2.1 ms (P < 0.05). We conclude
      that myogenic responses to magnetic transcranial stimulation are more sensitive
      to anesthetic-induced motoneural depression compared with those elicited by
      electrical transcranial stimulation. IMPLICATIONS: Transcranial motor evoked
      potentials are used to monitor spinal cord integrity intraoperatively. We
      compared the relative efficacy of electrical and magnetic transcranial stimuli in
      anesthetized patients. It seems that myogenic responses to magnetic transcranial
      stimulation are more sensitive to anesthetic-induced motoneural depression
      compared with electrical transcranial stimulation.

PMID- 10072008
TI  - Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine.
AB  - We sought to determine whether spinal clonidine 50 microg prolongs the analgesia
      from the spinal administration of sufentanil 7.5 microg and bupivacaine 2.5 mg
      early in the first stage of labor. Thirty patients were randomized to receive a 2
      mL spinal injection of sufentanil 7.5 microg + bupivacaine 2.5 mg with or without
      clonidine 50 microg using a combined spinal-epidural (CSE) technique. Pain,
      nausea, pruritus, sedation, motor block, blood pressure, and heart rate were
      assessed until the patient requested additional analgesia. Analgesia was
      significantly prolonged in patients who received spinal sufentanil + bupivacaine
      + clonidine (197 +/- 70 vs 132 +/- 39 min; P = 0.004). Pain scores and side
      effects, including motor block, sedation, and hypotension, were similar between
      groups. Spinal clonidine significantly prolongs labor analgesia from spinal
      sufentanil and bupivacaine without producing serious adverse side effects.
      IMPLICATIONS: We studied the effects of spinal clonidine administered with spinal
      sufentanil and bupivacaine on labor analgesia using a combined spinal-epidural
      technique and conclude that spinal clonidine significantly prolongs labor
      analgesia from spinal sufentanil and bupivacaine without producing serious
      adverse effects.

PMID- 10072009
TI  - The incidence of fetal heart rate changes after intrathecal fentanyl labor
      analgesia.
AB  - We performed a retrospective review to compare the incidence of new fetal heart
      rate abnormalities after institution of either intrathecal fentanyl or
      conventional epidural labor analgesia. In chronological order, the first 100
      parturients in active labor who had received epidural analgesia and had recorded
      fetal heart rate (FHR) traces for 30 min before and after injection were
      identified, as were the first 100 parturients who had received intrathecal
      fentanyl analgesia. A perinatologist blinded to the anesthetic technique
      evaluated each recording and identified any changes in the FHR between the before
      and after tracings. The incidence of new "negative" (implying worsened fetal
      status) changes was 6% in the epidural group and 12% in the intrathecal group (P
      > 0.05, not significant). There were no differences in incidence or degree of
      blood pressure change, need for cesarean delivery, neonatal outcome, parity, or
      oxytocin use. No parturient required urgent or emergent cesarean delivery, and
      all changes resolved within the 30-min observation period. A much larger study
      would be required to determine whether this six percentage point difference
      represents a true difference between groups, and its clinical significance.
      IMPLICATIONS: We compared the incidence of fetal heart rate changes after two
      techniques of labor analgesia. Both techniques were associated with a low (6%
      12%) incidence of changes, but a much larger series would be required to
      determine whether this represents a true difference. No difference in neonatal
      outcome was found.

PMID- 10072010
TI  - Pneumocephalus with intense headache and unilateral pupillary dilatation after
      accidental dural puncture during epidural anesthesia for cesarean section.

PMID- 10072011
TI  - The cesarean delivery of a twin gestation under 2 minimum alveolar anesthetic
      concentration isoflurane: one normal and one with a large neck mass.

PMID- 10072012
TI  - Pulmonary function changes after interscalene brachial plexus anesthesia with
      0.5% and 0.75% ropivacaine: a double-blinded comparison with 2% mepivacaine.
AB  - The purpose of this investigation was to compare, in a prospective, double
      blinded fashion, 0.5% and 0.75% ropivacaine with 2% mepivacaine to determine
      their effects on respiratory function during interscalene brachial plexus (IBP)
      anesthesia. With ethical committee approval and written, informed consent, 30
      healthy patients presenting for elective shoulder capsuloplastic or
      acromioplastic procedures were randomized to receive IBP anesthesia by 20 mL of
      either 0.5% ropivacaine (n = 10), 0.75% ropivacaine (n = 10), or 2% mepivacaine
      (n = 10). Block onset time, pulmonary function variables, ipsilateral
      hemidiaphragmatic motion (ultrasonographic evaluation), and first requirement of
      postoperative analgesic were evaluated. Surgical anesthesia (loss of pinprick
      sensation from C4 to C7 and motor block of the shoulder joint) was achieved later
      with 0.5% ropivacaine than with either 0.75% ropivacaine or 2% mepivacaine (P <
      0.05), whereas the first pain medication was requested later with both
      ropivacaine concentrations than with mepivacaine (P < 0.0005). No differences in
      quality of the block or patient acceptance were observed in the three groups. All
      30 patients had ipsilateral hemidiaphragmatic paresis and large mean decreases in
      forced vital capacity (ropivacaine 0.5%: 40% +/- 17%, ropivacaine 0.75%: 41% +/-
      22%, mepivacaine 2%: 39% +/- 21%) and forced expiratory volume at 1 s
      (ropivacaine 0.5%: 30% +/- 19%, ropivacaine 0.75%: 38% +/- 26%, mepivacaine 2%:
      40% +/- 10%). We conclude that, when performing IBP anesthesia, 0.5% ropivacaine
      does not decrease the incidence of ipsilateral paresis of the hemidiaphragm
      compared with 0.75% ropivacaine and 2% mepivacaine. IMPLICATIONS: During the
      first 30 min after placing interscalene brachial plexus anesthesia, 0.5%
      ropivacaine does not provide clinically relevant advantages in terms of pulmonary
      function changes compared with either 0.75% ropivacaine or 2% mepivacaine.
      However, 0.75% ropivacaine allows a short onset, similar to that of mepivacaine,
      with long postoperative analgesia.

PMID- 10072013
TI  - Magnetic resonance imaging demonstrates lack of precision in needle placement by
      the infraclavicular brachial plexus block described by Raj et al.
AB  - The infraclavicular brachial plexus block first described by Raj et al. was
      supposed to anesthetize all the main peripheral nerves of the brachial plexus
      without the risk of pneumothorax. However, in performing the block, we have had
      difficulties finding the nerves at the cord level. Therefore, we questioned
      whether the recommended needle direction (the "Raj line") guides the needle close
      enough to the cords. We therefore designed an anatomic study to answer this
      question and to assess the risks of entering the pleura and axillary vein. Ten
      volunteers were examined noninvasively in an open model magnetic resonance
      scanner. The Raj line deviated greatly from a defined location on the cords by a
      mean of 26 (range 14-39) mm, always caudad, and posterior to the target in nine
      cases. Further, the needle trajectory's shortest distance to the pleura was only
      10 (0-27) mm, and in one case, it hit the pleura. Finally, the Raj line's
      distance to the axillary vein was also short, 11 (0-18) mm. We conclude that a
      modification of the method is necessary to guide the needle closer to the cords
      and further away from the pleura and the axillary vein. A more lateral needle
      insertion seems beneficial. IMPLICATIONS: Using a magnetic resonance scanner, the
      anatomical basis of Raj's infraclavicular method for brachial plexus blockade was
      examined in volunteers. The results show that the method should be modified to
      make it more precise and to provide less risk of complications.

PMID- 10072014
TI  - The safety and efficacy of intrathecal opioid analgesia for acute postoperative
      pain: seven years' experience with 5969 surgical patients at Indiana University
      Hospital.
AB  - To assess the efficacy of the analgesic technique and the incidence of
      complications, we prospectively evaluated patients who received intrathecal
      opioid analgesia (ITOA) to manage postsurgical pain. Daily quality assurance data
      were collected on the first postoperative day and tabulated for 5969 adult
      patients who had received ITOA for major urologic, orthopedic, general/ vascular,
      thoracic, and nonobstetrical gynecologic surgery. A scale of 1-10 was used to
      quantify each patient's satisfaction with analgesia. The incidence of side
      effects, complications, and naloxone usage was also recorded and tabulated. The
      mean satisfaction score using a 10-point numeric rating scale was 8.51, with a
      score of 1 connoting "complete dissatisfaction" and 10 connoting "complete
      satisfaction." Side effects were minor and easily managed. Pruritus was the most
      common (37%). Respiratory depression was the least common (3%), easily detected
      by nursing observation, never life-threatening, and always responsive to
      treatment with naloxone. There were no deaths, nerve injuries, central nervous
      system infections, or naloxone-related complications. Postdural puncture
      headaches were rare (0.54%), as was the need for epidural blood patch (0.37%).
      IMPLICATIONS: Over a 7-yr period, intrathecal opioid analgesia was used to
      control acute postoperative pain on nearly 6000 patients, resulting in a high
      degree of patient satisfaction and a low incidence of side effects and
      complications.

PMID- 10072015
TI  - Adenosine reduces secondary hyperalgesia in two human models of cutaneous
      inflammatory pain.
AB  - Secondary hyperalgesia is characterized by increased sensitivity to noxious
      mechanical stimuli in the area surrounding injured skin. The pathophysiological
      mechanisms involve increased excitability of second-order neurons located in the
      spinal cord, i.e., central sensitization. The mechanisms behind this phenomenon
      may be of importance in clinical pain, including neuropathic pain. To study the
      effects of systemic infusion of the endogenous compound adenosine (ADO) on
      sensory function, a superficial cutaneous burn injury was induced by the 4-min
      topical application of mustard oil or by heat (47 degrees C for 7 min) during
      i.v. ADO infusion (60 microg x kg(-1) x min(-1)). Healthy human subjects (n = 10
      for each model) were tested, using a blinded, placebo-controlled procedure. The
      area of secondary hyperalgesia, as well as tactile and thermal sensory function,
      was tested using psychophysical methods during and after treatments. ADO
      significantly reduced the area of secondary hyperalgesia in both models. The
      maximal reduction compared with placebo was 58% +/- 20% (heat burn) and 39% +/-
      13% (mustard oil burn). No other differences in sensory function were observed.
      The results are interpreted as an ADO-induced modulatory effect on the mechanisms
      of central sensitization. IMPLICATIONS: We tested the effects of adenosine on the
      development of increased sensitivity in the skin surrounding a superficial skin
      injury in humans. A superficial skin bum was induced with a chemical irritant or
      heat. The results show that adenosine reduces the skin area with increased
      sensitivity surrounding the injury.

PMID- 10072016
TI  - A double-blinded evaluation of propacetamol versus ketorolac in combination with
      patient-controlled analgesia morphine: analgesic efficacy and tolerability after
      gynecologic surgery.
AB  - We assessed the relative morphine consumption in a combined analgesic regimen (on
      demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic
      surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g
      or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were
      monitored for 12 h, and the following efficacy variables were assessed: total
      dose of morphine, pain intensity, and global efficacy. Safety and tolerability
      were evaluated by the occurrence of adverse events, especially the presence and
      intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and
      60 min after the first infusion; arterial blood pressure, heart and respiratory
      rates, sedation scores, and renal and hepatic function were also assessed. Total
      morphine requirements were not significantly different between the propacetamol
      (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain
      intensity and the global efficacy also showed similar patterns in the two groups:
      70.2% of patients in the propacetamol group rated the efficacy as "good/
      excellent" compared with 68.2% in the ketorolac group. There were no clinically
      significant changes in vital signs or laboratory values and no observed
      differences between the two groups, although ketorolac slightly, but not
      significantly, prolonged the bleeding time. Epigastric pain was present in 9% and
      15% of patients receiving propacetamol and ketorolac, respectively. There were
      two adverse events in the propacetamol group and four in the ketorolac group.
      Propacetamol demonstrates an efficacy similar to that of ketorolac and has an
      excellent tolerability after gynecologic surgery. IMPLICATIONS: Propacetamol and
      ketorolac, combined with patient-controlled analgesia morphine, show similar
      analgesic efficacy after gynecologic surgery. Morphine consumption and pain
      scores were comparable in the two studied groups. Propacetamol is as effective as
      ketorolac and has an excellent tolerability after gynecologic surgery.

PMID- 10072017
TI  - Dexmedetomidine modulates cardiovascular responses to stimulation of central
      nervous system pressor sites.
AB  - Halothane attenuates the alterations in arterial pressure (BP) and heart rate
      (HR) produced by central nervous svstem (CNS) stimulation. We examined the
      effects of the alpha2-adrenergic agonist dexmedetomidine, with and without
      halothane, on cardiovascular regulation during CNS pressor site stimulation in
      chronically instrumented cats. Stimuli trains via bipolar stimulating electrodes
      in the hypothalamus and reticular formation elicited pressor responses.
      Dexmedetomidine-induced (15 microg/kg PO) bradycardia was greater in the presence
      of halothane. CNS stimulation increased BP and HR, which were dose-dependently
      attenuated by halothane (hypothalamic stimulation 71 +/- 9 mm Hg at control, 25
      +/- 5 and 15 +/- 3 mm Hg at 1.0% and 1.5% halothane, respectively). Although
      dexmedetomidine alone did not alter pressor responses, halothane plus
      dexmedetomidine attenuated pressor responses in a potentially synergistic fashion
      (hypothalamic stimulation 67 +/- 8 mm Hg at control, 2 +/- 1 and 1 +/- 0.4 mm Hg
      at 1.0% and 1.5% halothane, respectively). These results suggest differences in
      the disruptive effects of CNS-mediated cardiovascular responses by halothane and
      dexmedetomidine, and that dexmedetomidine has an anesthetic-sparing effect on
      these CNS-mediated cardiovascular control mechanisms, potentiating the depressant
      effect of halothane. IMPLICATIONS: A new potential anesthetic adjunct,
      dexmedetomidine, does not attenuate brain-mediated increases in blood pressure,
      but the combination of dexmedetomidine and the anesthetic halothane acts to
      modulate central cardiovascular responses.

PMID- 10072018
TI  - Pretreatment with dexmedetomidine: altered indices of anesthetic depth for
      halothane in the neuraxis of cats.
AB  - The sedative and anesthetic-sparing ability of the alpha2-adrenergic agonist
      dexmedetomidine is well documented. In this study, we identified the effects of
      halothane, with and without dexmedetomidine, on hemodynamic and
      electroencephalographic (EEG) variables and quantified the concentration of
      halothane resulting in various anesthetic depth indices mediated through the
      central nervous system (CNS) in chronically instrumented cats. Halothane was
      given alone or after dexmedetomidine (15 microg/kg p.o.). In both groups, four
      indices of anesthetic depth--minimum alveolar anesthetic concentration (MAC; no
      movement to noxious stimuli), MAC(BAR) (no autonomic response to noxious
      stimuli), MAC(BS) (EEG burst suppression), and MAC(ISOELECTRIC) (EEG
      isoelectricity)--were determined. Halothane decreased arterial blood pressure,
      heart rate, and higher frequency components of the EEG before the onset of burst
      suppression and isoelectricity. Dexmedetomidine pretreatment augmented the
      actions of halothane on arterial pressure, heart rate, and the EEG.
      Dexmedetomidine reduced the halothane concentrations resulting in MAC (from 1.22%
      +/- 0.06% to 0.89% +/- 0.08%) and MAC(BAR) (from 1.81% +/- 0.05% to 1.1% +/-
      0.10%), but not those resulting in MAC(BS) (3.01% +/- 0.17% vs 3.14% +/- 0.10%)
      or MAC(ISOELECTRIC) (4.39% +/- 0.26% vs 4.65% +/- 0.12%). These results suggest
      that dexmedetomidine does not alter various CNS-mediated indices of anesthetic
      action to equivalent degrees and that there are dissimilar degrees of an
      anesthetic-sparing action at different levels of the neuraxis. IMPLICATIONS: The
      anesthetic adjuvant dexmedetomidine seems to differentially alter central nervous
      system-mediated indices of anesthetic action. Lower brainstem or spinal
      determinants of anesthetic depth (movement and hemodynamic responses) are more
      attenuated than those of higher brain functions, such as the
      electroencephalogram.

PMID- 10072019
TI  - The effects of dexmedetomidine on neuromuscular blockade in human volunteers.
AB  - The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated
      the effect of dexmedetomidine on neuromuscular block and hemodynamics during
      propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the
      rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first
      response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium
      value. Dexmedetomidine was then administered by computer-controlled infusion,
      targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The
      evoked mechanical responses of the adductor pollicis responses (T1 response and
      T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted
      light through a fingertip were measured during the dexmedetomidine infusion and
      compared with predexmedetomidine values using repeated-measures analysis of
      variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to
      1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/-
      9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma
      rocuronium concentrations increased during the infusion (P = 0.02).
      Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min
      median values) during the infusion compared with values before the infusion.
      Dexmedetomidine increased the transmitted light through the fingertip by up to
      41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that
      dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium
      concentration, decreased T1, increased SBP, and decreased finger blood flow
      during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced
      vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We
      studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced
      neuromuscular block during propofol/alfentanil anesthesia. We found that the
      rocuronium concentration increased and the T1 response decreased during the
      dexmedetomidine administration. Although these effects were statistically
      significant, it is unlikely that they are of clinical significance.

PMID- 10072020
TI  - Pharmacokinetics and pharmacokinetic-dynamic relationship between rapacuronium
      (Org 9487) and its 3-desacetyl metabolite (Org 9488).
AB  - Rapacuronium (Org 9487) is a rapid-onset and short- to intermediate-acting muscle
      relaxant. Its 3-desacetyl metabolite, Org 9488, also exerts neuromuscular
      blocking activity that may become apparent after prolonged maintenance of
      relaxation with rapacuronium. In this study, the pharmacokinetic behavior (n = 7)
      of this metabolite and the pharmacokinetic/pharmacodynamic (PK/PD) relationship
      of rapacuronium (n = 10) and Org 9488 (n = 7) were investigated in humans.
      Similar protocols were used for three study groups regarding the anesthetic
      technique, blood and urine sampling, and pharmacokinetic and PK/PD analyses. The
      time course of action was measured mechanomyographically using the adductor
      pollicis muscle. The median clearance of rapacuronium was 7.28 mL x kg(-1) x min(
      1) x with an excretion fraction in the urine of 6.2%. The clearance (studied in
      two groups) of Org 9488 was 1.28 and 1.06 mL x kg(-1) x min(-1) with an excretion
      fraction in the urine of 51.9% and 53.5%, respectively. The median rate constant
      of transport between plasma and the biophase of rapacuronium (0.449 min(-1)) is
      markedly larger than that for Org 9488 (0.105 min(-1)). The modeled concentration
      in the biophase at 50% effect as a measure of potency is higher for rapacuronium
      (4.70 microg/mL) than for Org 9488 (1.83 microg/mL). The lower clearance of the
      metabolite will gradually prolong the time course of the neuromuscular blockade
      during maintenance with rapacuronium. IMPLICATIONS: We investigated the
      concentration-time-effect relationship of the relaxant rapacuronium and the
      contribution of its metabolite. Clearance, rate constant of transport between
      plasma and the biophase, and modeled concentration in the biophase at 50% effect
      of rapacuronium are consistent with its rapid onset and short to intermediate
      duration. The lower clearance of the metabolite will gradually prolong the time
      course of the neuromuscular blockade during maintenance with rapacuronium.

PMID- 10072021
TI  - The nature of spontaneous recovery from mivacurium-induced neuromuscular block.
AB  - The hypothesis of this study was that, in a given patient, recovery from a
      tracheal intubating dose of mivacurium would indicate the time course of
      spontaneous recovery after discontinuation of an infusion of mivacurium. Thirty
      eight male patients consented to participate in the study. After induction of
      anesthesia and endotracheal intubation, the ulnar nerve was stimulated with train
      of-four (TOF) stimuli at 12-s intervals. Patients received 0.3 mg/kg mivacurium
      in two evenly divided doses of 0.15 mg/kg each, separated by 30 s. Complete
      ablation of TOF responses occurred in most patients. Once the first twitch in the
      TOF (T ) had recovered to 25% of its baseline height, a mivacurium infusion was
      begun to maintain 95% suppression of T1. As surgery was nearing completion, the
      infusion was discontinued, and neuromuscular function was allowed to recover
      spontaneously. Data were analyzed for recovery intervals after the administration
      of the initial doses of mivacurium and after discontinuation of the infusion.
      Analysis of variance was used to determine the strength of correlation between
      the time from administration of the initial 0.3 mg/kg dose to 5% recovery of T1
      and the times to recovery of TOF ratios of 70% and 90%. The 25%-75% recovery
      interval after discontinuation of the infusion ranged from 2.8 to 11.3 min. The
      time interval after administration of mivacurium 0.3 mg/kg to 5% recovery of T1
      correlated with both the time to recovery of a TOF ratio of 70% and 90%. Recovery
      to a TOF of 90% after discontinuation of the infusion required approximately the
      same amount of time as recovery to 5% T1 after the administration of 0.3 mg/kg
      mivacurium. Each patient's recovery of neuromuscular function after
      discontinuation of a mivacurium infusion was related to his recovery after the
      administration of 0.3 mg/kg mivacurium. Therefore, the need for pharmacologic
      antagonism of block can be anticipated well before the end of an anesthetic.
      IMPLICATIONS: Mivacurium (0.3 mg/kg) was administered to 38 patients. As they
      began to recover muscle strength, a mivacurium infusion was begun and later
      discontinued as surgery was nearing completion. Each patient's early recovery
      (administration to 5% recovery of T1) after the initial dose of mivacurium
      correlated well with more complete recovery of muscle strength after
      discontinuation of an infusion. This relationship enables early prediction of
      recovery speed after a mivacurium infusion.

PMID- 10072022
TI  - Rabbits treated with chronic isepamicin are resistant to mivacurium and
      rocuronium.
AB  - We compared the dose-response relationships and the neuromuscular blocking
      effects of mivacurium and rocuronium after chronic isepamicin therapy for 7 days
      in 56 anesthetized rabbits. Train-of-four stimuli were applied every 10 s to the
      common peroneal nerve, and the force of contraction of the tibialis anterior
      muscle was measured. Chronic isepamicin therapy is associated with a rightward
      shift of the mivacurium and rocuronium dose-response curves. The effective dose
      for 50% twitch depression of mivacurium and rocuronium increased significantly,
      from 16.9 +/- 4.8 and 56.5 +/- 5.3 microg/kg, respectively, with placebo to 30.6
      +/- 5.3 and 75.6 +/- 4.7 microg/kg, respectively, during isepamicin therapy. The
      isepamicin rabbits receiving mivacurium 0.18 mg/kg or rocuronium 0.6 mg/kg had an
      accelerated recovery from neuromuscular blockade compared with those receiving
      placebo. The results of this study show that mivacurium and rocuronium have both
      a decreased effect and a shorter duration of action in rabbits when used during
      concurrent isepamicin therapy. IMPLICATIONS: We studied the dose-response
      relationships and the neuromuscular blocking effects of mivacurium and rocuronium
      during chronic isepamicin therapy in rabbits. Mivacurium and rocuronium have both
      a decreased effect and a shorter duration of action during chronic aminoglycoside
      antibiotic therapy in rabbits.

PMID- 10072023
TI  - The bispectral index: a measure of depth of sleep?
AB  - How does physiological sleep affect the Bispectral Index (BIS)? We collected
      electroencephalographic (EEG) data from five subjects during the early part of
      the night, comparing the changes in the BIS with the conventional EEG stages of
      sleep. We found that the BIS was a consistent marker of depth of sleep. Light
      sleep occurred at BIS values of 75-90, slow-wave sleep occurred at BIS values of
      20-70, and rapid eye movement sleep occurred at BIS values of 75-92. The effects
      of natural sleep on the BIS seem to be similar to the effects of general
      anesthesia on the BIS. The BIS may have a role in monitoring depth of sleep.
      IMPLICATIONS: Electroencephalographic data were collected from five subjects
      during sleep. We found that the Bispectral Index decreased during increasing
      depth of sleep in a fashion very similar to the decrease in Bispectral Index that
      occurs during general anesthesia. This study further highlights the
      electroencephalographic similarities of states of sleep and general anesthesia.

PMID- 10072024
TI  - The intubating laryngeal mask airway with and without fiberoptic guidance.
AB  - We conducted this feasibility study using the intubating laryngeal mask airway
      (ILMA) and a polyvinyl chloride tracheal tube to compare success rates,
      hemodynamic effects, and postoperative morbidity with two methods of tracheal
      intubation. After ethics approval and informed consent, 90 healthy ASA physical
      status I or II women with normal airways were enrolled in the randomized,
      controlled study. After a standardized inhaled anesthesia induction protocol,
      tracheal intubations using ILMA with fiberoptic guidance (ILMA-FOB) and ILMA
      inserted blindly without fiberoptic guidance (ILMA-Blind) were compared with the
      control group of direct laryngoscopy (laryngoscopy group). All 90 patients were
      successfully ventilated. For tracheal intubation, success rates were equal in all
      three groups (97%). Total intubation times were longer for the ILMA-FOB group (77
      s versus 48.5 s for laryngoscopy and 53.5 s for ILMA-Blind). The laryngoscopy
      group had a larger increase in mean arterial blood pressure to tracheal
      intubation. There were no differences in postoperative sore throat or hoarseness
      among the groups. In conclusion, success rates are equally high for tracheal
      intubation using ILMA-Blind and ILMA-FOB techniques in women with normal airways.
      IMPLICATIONS: The intubating laryngeal mask airway (ILMA) can be used as a
      primary airway for oxygenation and ventilation. Both methods of tracheal
      intubation using the ILMA were equally successful. Postoperative morbidity in the
      ILMA groups was similar to that in the laryngoscopy group. For women with normal
      airways, both the ILMA inserted blindly and the ILMA with fiberoptic guidance are
      suitable alternatives to laryngoscopy for tracheal intubation.

PMID- 10072025
TI  - Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical
      patients.
AB  - Drugs acting via the same mechanism interact additively, whereas a supraadditive
      effect can result from an interaction of drugs with different mechanisms of
      action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are
      supraadditive. In contrast to midazolam, the mechanisms of actions of propofol
      and thiopental are quite similar. The aim of this study was to test the
      hypothesis that similarity in the mechanisms of action of propofol and thiopental
      results in the additive hypnotic interaction. We studied the hypnotic effects of
      thiopental, propofol, and their combinations in 150 unpremedicated patients in a
      randomized, double-blind fashion. The ability to open eyes on command was used as
      an end point. Dose-response curves for the drugs given separately and in
      combinations at three different dose ratios between the drugs were determined by
      using a probit procedure, and the 50% effective dose values were compared by
      using isobolographic and algebraic (fractional) analysis. The hypnotic propofol
      thiopental combination was additive with all dose ratios between components of
      the combination. The absence of propofol-thiopental synergy, as demonstrated with
      midazolam-thiopental or propofol-midazolam combinations, suggests that the
      mechanisms underlying the hypnotic effects of propofol and thiopental, in
      contrast to the above combinations with midazolam, are very similar and could be
      identical. IMPLICATIONS: The propofol-thiopental hypnotic interaction is
      additive.

PMID- 10072026
TI  - The anesthetic and physiologic effects of an intravenous administration of a
      halothane lipid emulsion (5% vol/vol)
AB  - The i.v. administration of < or = 9 mL of nonvaporized liquid halothane causes
      significant pulmonary damage, cardiovascular decompensation, and death. To
      determine whether liquid halothane mixed in a lipid emulsion would alter these
      toxic effects, six swine were evaluated in a randomized cross-over study. The
      pulmonary, analgesic, hemodynamic, and histopathologic effects of liquid
      halothane (25 mL) mixed with a liquid carrier (475 mL, Liposyn III 20%) and
      administered by constant infusion were compared with halothane administered by a
      calibrated vaporizer. Three swine received the halothane lipid emulsion (HLE),
      followed by inhaled halothane. Three additional swine received inhaled halothane,
      followed by the HLE. There were no changes in pulmonary compliance or arterial
      blood gases during or after the administration of equivalent volumes of halothane
      (13.75 mL) either by infusion of HLE or by inhalation of halothane. The end-tidal
      halothane concentration for the minimum alveolar anesthetic concentration was
      0.79% +/- 0.08% during HLE administration and 1.13% +/- 0.12% for inhaled
      halothane (P < 0.001). Hemodynamic variables and blood halothane levels by gas
      chromatography were measured at end-tidal concentrations of 0.6%, 1.2%, and 1.8%.
      Blood halothane levels (mg/mL) were significantly higher (P < 0.05) after the
      administration of HLE at end-tidal halothane concentrations of 1.2% (0.49 +/-
      0.19 vs 0.82 +/- 0.18) and 1.8% (0.79 +/- 0.17 vs 1.29 +/- 0.34). When compared
      at equivalent blood levels, HLE caused fewer changes in the left ventricular end
      diastolic pressure, mean arterial pressure, and dP/dt than inhaled halothane.
      There was no evidence of pulmonary histopathologic damage 4-8 h after the
      infusion of 500-700 mL of HLE. This novel method of delivery of a volatile
      anesthetic seems to lack the toxicity of direct i.v. administration of liquid
      halothane. It may be a useful alternative to traditional administration via a
      vaporizer. IMPLICATIONS: Halothane causes pulmonary dysfunction and death when
      given i.v. in liquid form. Six swine received a halothane lipid emulsion i.v. to
      evaluate the anesthetic and physiologic effects. No pulmonary toxicity or deaths
      were associated with the halothane lipid emulsion. The anesthetic profile was
      similar to delivery of halothane via a vaporizer.

PMID- 10072027
TI  - The effects of general anesthetics on excitatory and inhibitory synaptic
      transmission in area CA1 of the rat hippocampus in vitro.
AB  - It is unclear whether general anesthetics induce enhancement of neural inhibition
      and/or attenuation of neural excitation. We studied the effects of pentobarbital
      (5 x 10(-4) mol/L), propofol (5 x 10(-4) mol/L), ketamine (10(-3) mol/L),
      halothane (1.5 vol%), and isoflurane (2.0 vol%) on both excitatory and inhibitory
      synaptic transmission in rat hippocampal slices. Excitatory or inhibitory
      synaptic pathways were isolated using pharmacological antagonists. Extracellular
      microelectrodes were used to record electrically evoked CA1 neural population
      spikes (PSs). In the presence of the gamma-aminobutyric acid type A (GABA(A))
      receptor antagonist (bicuculline), the inhibitory actions of pentobarbital and
      propofol were completely antagonized, whereas those of ketamine, halothane, and
      isoflurane were only partially blocked. To induce the N-methyl-D-aspartate (NMDA)
      receptor-mediated PS (NMDA PS), the non-NMDA and GABA(A) receptors were blocked
      in the absence of Mg2+. Ketamine, halothane, and isoflurane decreased the NMDA
      PS, and pentobarbital and propofol had no effect on the NMDA PS. The non-NMDA
      receptor-mediated PS (non-NMDA PS) was examined using the antagonists for the
      NMDA and GABA(A) receptors. Volatile, but not i.v., anesthetics reduced the non
      NMDA PS. These findings indicate that pentobarbital and propofol produce
      inhibitory actions due to enhancement in the GABA(A) receptor; that ketamine
      reduces NMDA receptor-mediated responses and enhances GABA(A) receptor-mediated
      responses; and that halothane and isoflurane modulate GABA(A), NMDA, and non-NMDA
      receptor-mediated synaptic transmission. IMPLICATIONS: Volatile anesthetics
      modulate both excitatory and inhibitory synaptic transmission of in vitro rat
      hippocampal pathways, whereas i.v. anesthetics produce more specific actions on
      inhibitory synaptic events. These results provide further support the idea that
      general anesthetics produce drug-specific and distinctive effects on different
      pathways in the central nervous system.

PMID- 10072028
TI  - Isoflurane depresses motoneuron excitability by a direct spinal action: an F-wave
      study.
AB  - Isoflurane decreases motoneuron excitability as measured by the F wave. It is
      unknown how much of this effect is direct and how much occurs as the result of an
      indirect, supraspinal effect. Seven goats were anesthetized with isoflurane, and
      the carotid arteries and jugular veins were isolated to permit cranial bypass.
      Isoflurane was delivered to the head via a bypass-oxygenator unit and to the
      torso via the lungs. Evoked gastrocnemius muscle potentials were measured after
      supramaximal electrical stimulation of the ischiatic nerve. F- and M-wave
      amplitudes and F-wave latencies were determined from 20 evoked responses obtained
      at each of the following head/torso isoflurane concentrations: 0.8%/0.3%,
      1.3%/0.3%, 3%/0.3%, 0.3/0.8%, and 1.3%/0.8%. When the torso isoflurane was 0.3%,
      increasing the cranial isoflurane concentration from 0.8% to 1.3% did not
      significantly affect the F/M amplitude ratio (from 0.188 +/- 0.166 to 0.194 +/-
      0.124; P > 0.05), but the ratio decreased approximately 50% when the cranial
      isoflurane was 3% (to 0.088 +/- 0.078; P < 0.05). F-wave latency was not affected
      by changing the cranial isoflurane concentration. The F/M amplitude ratio
      decreased 80%-85% when isoflurane 0.8% was administered to the torso and was not
      measurable in five animals; at this torso concentration, changing the cranial
      concentration from 0.3% to 1.3% had no effect on the F/M ratio (from 0.042 +/-
      0.065 to 0.030 +/- 0.041; P > 0.05). In goats, motoneuron excitability is very
      sensitive to the direct action of isoflurane, and supraspinal effects occur
      between cranial isoflurane concentrations of 1.3% and 3%. IMPLICATIONS: We
      studied the effect of isoflurane action in the brain on motoneuron excitability,
      using the F wave. We found that the F wave is very sensitive to the direct action
      of isoflurane and that cranial isoflurane has indirect effects between
      concentrations of 1.3% and 3%.

PMID- 10072029
TI  - A comparison among nalbuphine, meperidine, and placebo for treating
      postanesthetic shivering.
AB  - Postanesthetic shivering (PS) is distressing for patients and may induce a
      variety of complications. In this prospective, double-blinded, randomized study,
      we evaluated the value of nalbuphine, compared with meperidine and saline, for
      treating PS. Ninety adult patients were included in the study. Group 1 (n = 30)
      received i.v. nalbuphine 0.08 mg/kg, Group 2 (n = 30) received i.v. meperidine
      0.4 mg/kg, and Group 3 (n = 30) received i.v. saline. Treatment that stopped
      shivering was considered to have been successful. The results demonstrated that,
      5 min after treatment, both nalbuphine and meperidine provided a rapid and potent
      anti-shivering effect on PS, with high response rates of 80% and 83%, compared
      with those of saline (0%) (P < 0.01). Thirty minutes after injection, the
      response rates of nalbuphine and meperidine were 90% and 93%, respectively,
      compared with 17% in the saline group (P < 0.01). The differences between
      nalbuphine and meperidine were not significant. We conclude that nalbuphine may
      be an alternative to meperidine for treating PS. IMPLICATIONS: We evaluated
      nalbuphine versus meperidine and saline for treating postanesthetic shivering.
      Our results demonstrate that both nalbuphine and meperidine provide a similar
      rapid and potent anti-shivering effect. Nalbuphine may be an alternative to
      meperidine for treating postanesthetic shivering.

PMID- 10072030
TI  - Inhaled nitric oxide and amniotic fluid embolism.

PMID- 10072031
TI  - Modified esophageal detector device.

PMID- 10072032
TI  - Transfusion requirements in orthotopic liver transplantation.

PMID- 10072033
TI  - External jugular vein cannulation for central venous access.

PMID- 10072034
TI  - Use of the laryngeal mask airway in children with upper respiratory tract
      infections: beware secretions.

PMID- 10072035
TI  - Is there a responsibility to disclose data used as the basis for a publication?

PMID- 10072036
TI  - An unusual cause of a double-lumen endotracheal tube obstruction.

PMID- 10072037
TI  - Vasopressin and postcardiopulmonary bypass refractory hypotension.

PMID- 10072038
TI  - A simple technique for oral fiberoptic bronchoscopy: "No more needles, Doc".

PMID- 10072040
TI  - A new look at neuropathology in sickle cell disease.

PMID- 10072039
TI  - Hypoxic ventilatory response: the effects of CO2 and of sustained hypoxia.

PMID- 10072041
TI  - Subtle brain abnormalities in children with sickle cell disease: relationship to
      blood hematocrit.
AB  - Our objective was to test a hypothesis that subtle brain abnormality can be
      present in pediatric sickle cell disease (SCD) patients who are clinically free
      of stroke. We prospectively compared 50 patients with 52 healthy age-similar
      controls, using quantitative magnetic resonance imaging. A previously validated
      precise and accurate inversion-recovery method was used to measure T1 in a slice
      at the basal ganglia. We also used the Wechsler test to measure intelligence
      quotient (IQ) in a randomly selected subset of 27 patients. Brain T1 was
      significantly lower in patients in every gray matter structure evaluated but in
      none of the white matter structures. Regression suggests that T1 in caudate,
      nucleus pulvinares, and cerebral cortex was abnormal by age 4 years. Psychometric
      testing showed that 33% of patients were functioning in the range of mild mental
      deficiency (IQ, 50-70), compared with a published prevalence of 1.45% in inner
      city black children. Thus, in our patients, SCD was associated with a 23-fold
      increase in the risk of mild mental deficiency. Full-scale IQ of SCD patients was
      a function of hematocrit (Hct), and when Hct was used to stratify patients, those
      with an Hct of less than 27% had significantly lower psychometric test scores,
      and significantly lower gray matter T1, than those with an Hct of 27 or more.
      Both cognitive deficits and subtle T1 abnormalities were associated with a low
      Hct, and both could be present when conventional magnetic resonance imaging
      findings were normal. Our findings suggest that chronic hypoxia of brain tissue
      can occur in SCD patients free of clinical stroke.

PMID- 10072042
TI  - Developmental changes in brain serotonin synthesis capacity in autistic and
      nonautistic children.
AB  - Serotonin content, serotonin uptake sites, and serotonin receptor binding
      measured in animal studies are all higher in the developing brain, compared with
      adult values, and decline before puberty. Furthermore, a disruption of synaptic
      connectivity in sensory cortical regions can result from experimental increase or
      decrease of brain serotonin before puberty. The purpose of the present study was
      to determine whether brain serotonin synthesis capacity is higher in children
      than in adults and whether there are differences in serotonin synthesis capacity
      between autistic and nonautistic children. Serotonin synthesis capacity was
      measured in autistic and nonautistic children at different ages, using
      alpha[11C]methyl-L-tryptophan and positron emission tomography. Global brain
      values for serotonin synthesis capacity (K complex) were obtained for autistic
      children (n = 30), their nonautistic siblings (n = 8), and epileptic children
      without autism (n = 16). K-complex values were plotted according to age and
      fitted to linear and five-parameter functions, to determine developmental changes
      and differences in serotonin synthesis between groups. For nonautistic children,
      serotonin synthesis capacity was more than 200% of adult values until the age of
      5 years and then declined toward adult values. Serotonin synthesis capacity
      values declined at an earlier age in girls than in boys. In autistic children,
      serotonin synthesis capacity increased gradually between the ages of 2 years and
      15 years to values 1.5 times adult normal values and showed no sex difference.
      Significant differences were detected between the autistic and epileptic groups
      and between the autistic and sibling groups for the change with age in the
      serotonin synthesis capacity. These data suggest that humans undergo a period of
      high brain serotonin synthesis capacity during childhood, and that this
      developmental process is disrupted in autistic children.

PMID- 10072043
TI  - Therapeutic benefit of ciliary neurotrophic factor in progressive motor
      neuronopathy depends on the route of delivery.
AB  - Ciliary neurotrophic factor (CNTF) has demonstrated therapeutic effects in
      several mouse mutants with motoneuronal degeneration. However, the poor
      bioavailability and toxic side effects of recombinant CNTF protein have
      complicated its use in patients with amyotrophic lateral sclerosis. CNTF gene
      transfer strategies were developed but faced the question of whether CNTF should
      be delivered to motoneuron cell bodies or to their axons or muscle targets. To
      address this issue, we have used an adenoviral vector (AdCNTF) coding for a
      secretable form of CNTF and compared different routes of its administration in
      the mouse mutant progressive motor neuronopathy (pmn). Intramuscular,
      intravenous, and intracerebroventricular injections of AdCNTF or the control
      vector AdlacZ resulted in transgene expression in skeletal muscle fibers,
      hepatocytes, and ependymal cells, respectively, as determined by histochemistry
      and reverse transcription-polymerase chain reaction. AdCNTF intramuscularly
      treated and intravenously treated pmn mice showed a 25% increase in mean life
      span and a reduced degeneration of phrenic myelinated nerve fibers, which
      correlated with elevated CNTF serum bioactivities. In contrast,
      intracerebroventricular AdCNTF administration did not affect the mean life span
      or motor axonal degeneration of pmn mice. The differential efficacy of peripheral
      and central CNTF vector administrations might be of interest for future studies
      in human motor neuron diseases.

PMID- 10072044
TI  - Gelsolin-related spinal and cerebral amyloid angiopathy.
AB  - Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare
      disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene
      mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy
      are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor
      cognitive impairment may occur. In histological and immunohistochemical studies
      of the central nervous system in 4 patients with a G654A gelsolin mutation, we
      found widespread spinal, cerebral, and meningeal amyloid angiopathy, with
      deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits
      occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid
      deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1
      antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular
      fibrinogen immunoreactivity was occasionally noted. The patients showed posterior
      column degeneration and diffuse loss of myelin in the centrum semiovale with
      perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1
      patient, showed white matter lesions, colocalizing with the histological
      abnormalities. Our study shows that deposition of AGel in the spinal and cerebral
      blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia
      is an essential feature of this form of systemic amyloidosis and may contribute
      to the central nervous system symptoms.

PMID- 10072045
TI  - Spatial memory deficits in patients with lesions affecting the medial temporal
      neocortex.
AB  - Lesion studies in monkeys suggest that neocortical subregions of the medial
      temporal lobe (MTL) carry memory functions independent of the hippocampal
      formation. The present study investigates possible differential contributions of
      MTL subregions to spatial memory in humans. Eye movements toward remembered
      spatial cues (memory-guided saccades) with unpredictably varied memorization
      delays of up to 30 seconds were recorded in patients with postsurgical lesions of
      the right MTL, either restricted to the hippocampal formation (n = 3) or
      including the adjacent neocortex (n = 5) and in 10 controls. Although saccadic
      targeting errors of patients with selective hippocampal lesions did not differ
      from controls, saccadic targeting errors of patients with additional neocortical
      involvement showed a significant and contralaterally pronounced increase at
      memorization delays above 20 seconds. We conclude that the human medial temporal
      neocortex carries spatial memory functions independent of the hippocampal
      formation and distinct from spatial short-term memory.

PMID- 10072046
TI  - Biochemical features of mtDNA 14484 (ND6/M64V) point mutation associated with
      Leber's hereditary optic neuropathy.
AB  - We report the effect on complex I function of the 14484 Leber's hereditary optic
      neuropathy (LHON) mutation affecting the ND6 subunit gene. The same gene was also
      reported to carry another mutation, at position 14459, associated with the
      LHON/dystonia phenotype that induces a reduction of complex I-specific activity
      and increases the sensitivity to the product decylubiquinol. Given the proximity
      of both mutations in the ND6 gene, we tested the specific activity of complex I
      and its sensitivity to myxothiazol and nonylbenzoquinol, both inhibitors at the
      ubiquinol product site, in platelet submitochondrial particles from nine 14484
      homoplasmic individuals, 8 Italians with Caucasian mtDNA haplogroup J (adjunctive
      4216 and 13708 mutations), and 1 Tunisian with an African mtDNA haplogroup. The
      specific activity of complex I was not affected by the 14484 mutation, but the
      sensitivity to both inhibitors was significantly increased compared with control
      subjects regardless of the presence of haplogroup J polymorphisms. Analysis of 70
      different amino acid sequences of the ND6 subunit indicated that the 14484
      mutation affects an amino acid belonging to its most conserved region, which
      shows local similarities with cytochrome b regions interacting with ubiquinone or
      ubiquinol in complex III. Our results suggest that both 14484 and 14459 mutations
      may affect amino acids forming the interaction site of ubiquinol product, and the
      14484 mutation produces a biochemical defect resembling in part that already
      reported for the common 11778/ND4 LHON mutation.

PMID- 10072047
TI  - Enhanced lateral premotor activity during paradoxical gait in Parkinson's
      disease.
AB  - Parkinson's disease (PD) patients often show marked improvement of hypokinetic
      gait when exposed to special stimuli. To investigate physiological mechanisms
      underlying this "paradoxical gait" induced by visual cues in PD patients, we
      examined regional cerebral blood flow changes during gait on a treadmill guided
      by two different visual cues, the lines oriented transversely to the direction of
      walk (TL) and the lines parallel to it (PL). Ten PD patients and 10 age-matched
      controls received injections of 99mTc-hexamethylpropyleneamine oxime twice, once
      during each walking condition. Brain perfusion images were obtained by single
      photon emission computed tomography. When affected by TL, PD patients showed
      marked improvement of gait parameters, mainly reduction of cadence. In regional
      cerebral blood flow analysis, when TL was compared with PL, both groups had
      common activation in the posterior parietal cortex and cerebellar hemispheres.
      Especially in the right lateral premotor cortex, PD patients showed enhanced
      activation induced by TL to a significantly greater degree than the controls. The
      present study indicates that the network dedicated to visuomotor control,
      particularly the lateral premotor cortex, plays an important role in the
      development of the paradoxical gait induced by special visual stimuli in PD
      patients.

PMID- 10072048
TI  - Abnormal fatty acid metabolism in childhood spinal muscular atrophy.
AB  - Our previous experience with abnormal fatty acid metabolism in several children
      with spinal muscular atrophy (SMA) prompted evaluation of fatty acid metabolism
      in a larger cohort. Thirty-three infants with severe infantile SMA were shown to
      have a significantly increased ratio of dodecanoic to tetradecanoic acid in
      plasma compared with normal infants and 6 infants affected with equally
      debilitating, non-SMA denervating disorders. Seventeen children with milder forms
      of SMA had normal fatty acid profiles. In addition, all 5 infants with severe SMA
      evaluated in a fasting state developed a distinctive and marked dicarboxylic
      aciduria, including saturated, unsaturated, and 3-hydroxy forms, comparable in
      severity with the dicarboxylic aciduria of children with primary defects of
      mitochondrial fatty acid beta-oxidation. Nine children with chronic SMA and 23
      control patients did not develop an abnormal dicarboxylic aciduria during
      fasting. No known disorder of fatty acid metabolism explains all of the
      abnormalities we find in SMA. Our data suggest, however, that the abnormalities
      are not a consequence of SMA-related immobility, systemic illness, muscle
      denervation, or muscle atrophy. These abnormalities in fatty acid metabolism may
      be caused by changes in cellular physiology related to the molecular defects of
      the SMA-pathogenic survival motor neuron gene or neighboring genes.

PMID- 10072049
TI  - Autosomal recessive rolandic epilepsy with paroxysmal exercise-induced dystonia
      and writer's cramp: delineation of the syndrome and gene mapping to chromosome
      16p12-11.2.
AB  - We describe a pedigree in which 3 members in the same generation are affected by
      Rolandic epilepsy (RE), paroxysmal exercise-induced dystonia (PED), and writer's
      cramp (WC). Both the seizures and paroxysmal dystonia had a strong age-related
      expression that peaked during childhood, whereas the WC, also appearing in
      childhood, has been stable since diagnosis. Genome-wide linkage analysis
      performed under the assumption of recessive inheritance identified a common
      homozygous haplotype in a critical region spanning 6 cM between markers D16S3133
      and D16S3131 on chromosome 16, cosegregating with the affected phenotype and
      producing a multipoint LOD score value of 3.68. Although its features are unique,
      this syndrome presents striking analogies with the autosomal dominant infantile
      convulsions and paroxysmal coreoathetosis (ICCA) syndrome, linked to a 10 cM
      region between D16S401 and D16S517, which entirely includes the 6 cM of the RE
      PED-WC critical region. The same gene may be responsible for both RE-PED-WC and
      ICCA, with specific mutations explaining each of these Mendelian disorders. This
      report shows that idiopathic focal disorders such as epilepsy and dystonia, can
      be caused by the same genetic abnormality, may have a transient expression, and
      may be inherited as an autosomal recessive trait.

PMID- 10072050
TI  - Antibodies to alpha-synuclein detect Lewy bodies in many Down's syndrome brains
      with Alzheimer's disease.
AB  - Immunohistochemical examination of 20 Down's syndrome brains, using antibodies to
      alpha-, beta-, and gamma-synuclein, demonstrated many alpha-synuclein-positive
      Lewy bodies and dystrophic neurites in 50% of amygdala samples from Down's
      syndrome brains with Alzheimer's disease. Similar lesions were less common in
      other regions of these brains, none of which contained beta-synuclein or gamma
      synuclein abnormalities. Thus, alpha-synuclein-positive Lewy bodies and neuritic
      processes frequently occur with Alzheimer's disease in Down's syndrome brains.

PMID- 10072051
TI  - Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease.
AB  - The distribution and density of neurofibrillary tangles and amyloid plaques was
      studied in a unique series of cases whose premortem cognitive status had been
      assessed with the Clinical Dementia Rating (CDR), including 39 nondemented cases
      (CDR = 0; age, 51-88 years), 15 very mildly demented cases (CDR = 0.5), and 8
      severely demented (CDR = 3) cases. The initial formation of tangles and plaques
      in healthy aging appeared to be independent of each other. Tangles were found in
      all the nondemented cases, especially in hippocampal and parahippocampal areas;
      the average tangle concentration increased exponentially with age. In contrast,
      plaques were absent in some brains up to age 88, and the earliest plaque
      formation in other cases occurred in the neocortex, in patches of diffuse
      plaques. Widely distributed neuritic as well as diffuse plaques throughout
      neocortex and limbic structures characterized a further group of nondemented
      cases. In these cases there was also a substantial increase over other
      nondemented cases, both in the number of tangles and in the rate of increase in
      tangles with age, suggesting an interaction between amyloid and neurofibrillary
      change at this stage. Such cases closely resemble CDR = 0.5 cases, and it is
      proposed they represent "preclinical" Alzheimer's disease.

PMID- 10072052
TI  - Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic
      resonance imaging-negative temporal lobe epilepsy: different biochemical profile
      compared with hippocampal sclerosis.
AB  - Single-voxel proton magnetic resonance spectroscopy (1H MRS) has shown
      abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal
      sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on
      quantitative magnetic resonance imaging (MRI) (MRI-negative). Fifteen control
      subjects, 15 patients with unilateral HS, and 15 MRI-negative TLE patients
      underwent 1H MRS at an echo time of 30 msec on a 1.5-T GE Signa scanner. Voxels
      were tailored to the individual hippocampi. N-Acetylaspartate (NAA), creatine,
      choline, total glutamate plus glutamine (Glx), and myo-inositol (Ins) were
      quantitated by using an external standard and LCModel, a user-independent
      quantitation method. Normal ranges were defined as the control mean +/- 2.5 SD.
      In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of
      these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins
      ratios lateralized the side affected by HS in 7 of 15 patients, without any
      bilateral abnormalities. In 15 MRI-negative TLE patients, 4 had abnormally low
      hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA
      bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA,
      most marked in patients with HS and on the side of seizure onset. The mean
      NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI
      negative patients. The concentration of Glx was higher ipsilateral to seizure
      onset in MRI-negative patients than in HS patients. Quantitative short echo time
      1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI
      negative TLE patients in concordance with other lateralizing data. In individual
      and group comparisons, 1H MRS described a metabolite profile in the hippocampi of
      MRI-negative TLE patients that was different from patients with HS, with an
      increase in Glx and a less marked decrease in NAA than was seen in HS.

PMID- 10072053
TI  - Kearns-Sayre syndrome: unusual pattern of expression of subunits of the
      respiratory chain in the cerebellar system.
AB  - Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder of oxidative
      phosphorylation associated with clonally expanded rearrangements of mitochondrial
      DNA (mtDNA). Mitochondrial dysfunction in the central nervous system of patients
      with KSS accounts for the neurological manifestations of the disease. To gain
      further insight into the pathogenesis of neuronal dysfunction in KSS, we used
      antibodies against mtDNA-encoded and nuclear DNA-encoded subunits of the
      mitochondrial respiratory chain to study the expression of these proteins in the
      cerebellar cortex, dentate nucleus, and inferior olivary nucleus from 2 autoptic
      cases of KSS. Neuropathological examination showed a moderate loss of Purkinje
      cells and spongiform degeneration of the cerebellar white matter. By using
      immunohistochemistry, we found a decreased expression of mtDNA-encoded proteins
      only in neurons of the dentate nucleus. We suggest that mitochondrial
      abnormalities in the dentate nucleus in conjunction with loss of Purkinje cells
      and spongiform degeneration of the cerebellar white matter may be important
      factors in the genesis of the cerebellar dysfunction in KSS.

PMID- 10072054
TI  - Involvement of cranial muscles and high intermuscular coherence in orthostatic
      tremor.
AB  - Electromyographic recordings were conducted from limb, trunk, and cranial muscles
      in 6 patients with orthostatic tremor. Spectral analysis revealed a high
      frequency tremor not only in the muscles of the limbs and trunk, but also in
      cranial muscles. The cross spectra were analyzed between various pairs of muscles
      that displayed a high-frequency tremor pattern. The resulting peak correlations
      were uniformly very high (near one) suggesting a high level of coherence. The
      involvement of cranial muscles suggests that supraspinal mechanisms are involved
      in the generation of orthostatic tremor. The high intermuscular coherence between
      all muscles indicates the existence of either a unique oscillator that generates
      tremor in all involved muscles on both sides of the body or a linking mechanism
      probably at a supraspinal level. The high-frequency tremor was only found when
      the muscles were contracted isometrically, irrespective of body posture. Thus,
      tremor generation might be more closely linked to mechanisms responsible for
      isometric force control than to those involved in stance regulation.

PMID- 10072055
TI  - Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency.
AB  - Stroke-like episodes, defined as periods of acute localized neurological
      dysfunction during which brain imagery suggests cerebral ischemia but vascular
      anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac
      St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal
      neurological deterioration and frontal hypodensities on cerebral computerized
      tomography (CT). Arteriography, performed in 1 patient during an acute episode,
      showed normal vascular anatomy. Nevertheless, capillary shunting was evident both
      in regions that appeared abnormal on the initial cerebral CT study and in regions
      that appeared normal but subsequently developed Leigh disease. Stroke-like
      episodes did not exacerbate systemic acidosis, and acidotic decompensations
      occurred independently of stroke-like episodes. In conclusion, stroke-like
      episodes occur in autosomal recessively inherited congenital lactic acidoses as
      well as in those caused by mitochondrial DNA mutations. In some cases, acute
      localized neurovascular changes occur in regions that subsequently develop Leigh
      disease.

PMID- 10072056
TI  - Radiation-induced cerebral vasculopathy in children with neurofibromatosis and
      optic pathway glioma.
AB  - Occlusive vasculopathy is a potential complication of radiotherapy in children
      with optic pathway glioma. With a median follow-up of 7 years, 13 of 69 children
      in this study developed clinical and radiological signs of occlusive vasculopathy
      after radiotherapy within a median interval of 36 months. The major risk factor
      was neurofibromatosis type 1. Radiotherapy should no longer be the first
      treatment in these settings. When radiotherapy is unavoidable, regular screening
      for cerebral vasculopathy is mandatory, as preventive treatment is available.

PMID- 10072057
TI  - HLA A2 allele is associated with age at onset of Alzheimer's disease.
AB  - The prevalence of the HLA A2 allele was investigated in a group of Italian
      patients with sporadic and early-onset familial Alzheimer's disease (AD and FAD)
      to analyze the potential association of this allele with early age of onset of
      the disease. The possible interaction between the HLA A2 allele and
      apolipoprotein E epsilon4 allele was analyzed. Our data suggest that A2 and
      epsilon4 alleles may have additive effects on AD onset, and that A2 may play an
      important role in determining or contributing to a very early age at onset. These
      findings further support the hypothesis of the involvement of an
      immune/inflammatory mechanism in the pathogenesis of AD.

PMID- 10072058
TI  - Monospecific anti-GD1b IgG is required to induce rabbit ataxic neuropathy.
AB  - Of 22 rabbits sensitized with GD1b, 12 developed experimental sensory ataxic
      neuropathy. The affected rabbits had a higher level of serum IgG monospecific to
      GD1b than the unaffected ones. The GD1b-positive neuronal cytoplasms of rabbit
      dorsal root ganglia had larger diameters than the negative ones. IgG antibody
      monospecific to GD1b may preferentially bind to large primary sensory neurons,
      causing sensory ataxic neuropathy.

PMID- 10072059
TI  - Cerebral tumor-like American trypanosomiasis in acquired immunodeficiency
      syndrome.
AB  - Cerebral tumor-like American trypanosomiasis (CTLAT) is an uncommon complication
      of Chagas' disease, observed only in immunosuppressed patients. We assessed 10
      human immunodeficiency virus-positive patients with Chagas' disease who presented
      with CTLAT. All patients had neurological involvement and 6 developed
      intracranial hypertension. Neuroimaging studies showed supratentorial lesions in
      9 patients, being single in 8. One case had infratentorial and supratentorial
      lesions. Low CD4+ cell counts were observed in all the cases and in 6 of them
      CTLAT was the first manifestation of acquired immunodeficiency syndrome.
      Serological tests for Chagas' disease were positive in 6 of 8 patients.
      Trypanosoma cruzi was identified in all brain specimens and in three
      cerebrospinal fluid samples. CTLAT should be considered in the differential
      diagnosis of intracranial mass lesions in human immunodeficiency virus-positive
      patients and should be added to the list of acquired immunodeficiency syndrome
      defining illnesses.

PMID- 10072060
TI  - Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs
      and epilepsy.
AB  - We investigated a family with a new type of autosomal dominant cerebellar ataxia
      (ADCA) in which pure cerebellar ataxia is often accompanied with epilepsy. No CAG
      repeat expansions were detected at the spinocerebellar ataxia (SCA) type 1, 2, 3,
      6, or 7 locus, and SCAs 4 and 5 were excluded by linkage analysis. We found
      linkage between the disease locus and D22S274 (Zmax = 3.86 at theta = 0.00) and
      two other makers in 22q13-qter. Haplotype analysis of the crossover events and
      the multipoint linkage mapping localized the disease locus to an 8.8-cM region
      between D22S1177 and D22S1160.

PMID- 10072061
TI  - Silent intracerebral microhemorrhages in stroke patients.

PMID- 10072062
TI  - Administration of nitric oxide synthase inhibitors does not alter disease course
      of amyotrophic lateral sclerosis SOD1 mutant transgenic mice.

PMID- 10072063
TI  - Endocrine function in Lambert-Eaton myasthenic syndrome.

PMID- 10072064
TI  - Cortical excitability in migraine.

PMID- 10072065
TI  - Phosphene generation in migraine.

PMID- 10072066
TI  - Other functions, other genes: alternative activation of antigen-presenting cells.

PMID- 10072067
TI  - CREB regulates MHC class II expression in a CIITA-dependent manner.
AB  - The X2 box of MHC class II promoters is homologous to TRE/CRE elements and is
      required for expression of MHC class II genes. The X2 box-specific DNA binding
      activity, X2BP, was purified to homogeneity, sequenced, and identified as CREB.
      Transient transactivation experiments showed that CREB can cooperate with CIITA
      to enhance activation of transcription from MHC class II promoters in a dose
      dependent manner. Binding of CREB to the class II promoter in vivo was
      demonstrated by a chromatin immunoprecipitation assay. Additionally, ICER, a
      dominant inhibitor of CREB function, was found to repress class II expression.
      These results demonstrate that CREB binds to the X2 box in vivo and cooperates
      with CIITA to direct MHC class II expression.

PMID- 10072068
TI  - RFX-B is the gene responsible for the most common cause of the bare lymphocyte
      syndrome, an MHC class II immunodeficiency.
AB  - The bare lymphocyte syndrome (BLS) is characterized by the absence of MHC class
      II transcription and humoral- and cellular-mediated immune responses to foreign
      antigens. Three of the four BLS genetic complementation groups have defects in
      the activity of the MHC class II transcription factor RFX. We have purified the
      RFX complex and sequenced its three subunits. The sequence of the smallest
      subunit describes a novel gene, termed RFX-B. RFX-B complements the predominant
      BLS complementation group (group B) and was found to be mutant in cell lines from
      this BLS group. The protein has no known DNA-binding domain but does contain
      three ankyrin repeats that are likely to be important in protein-protein
      interactions.

PMID- 10072069
TI  - A defect in the nuclear translocation of CIITA causes a form of type II bare
      lymphocyte syndrome.
AB  - The severe immunodeficiency type II bare lymphocyte syndrome (BLS) lacks class II
      MHC gene transcription. One defect from a complementation group A type II BLS
      patient is a 24 aa deletion in the MHC class II transactivator (CIITA). We show
      here that the molecular defect present in this protein is a failure of CIITA to
      undergo nuclear translocation. This defect was mapped to a position-dependent,
      novel nuclear localization sequence that cannot be functionally replaced by a
      classical NLS. Fusion of this 5 aa motif to an unrelated protein leads to nuclear
      translocation. Furthermore, this motif is not critical for transactivation
      function. This is a description of a genetic disease resulting from a novel
      defect in the subcellular localization of a transcriptional coactivator.

PMID- 10072070
TI  - Functional characterization of a novel hematopoietic stem cell and its place in
      the c-Kit maturation pathway in bone marrow cell development.
AB  - While the majority of purified pluripotential hematopoietic stem cells (PHSC)
      express c-Kit, the receptor for steel factor, we have phenotypically and
      functionally separated a distinct class of PHSC that does not express c-Kit. In
      contrast to c-Kit-positive (c-Kit(pos)) PHSC, the c-Kit-negative (c-Kit(neg))
      PHSC do not proliferate in response to multiple hematopoietic growth factors in
      vitro and do not radioprotect or form macroscopic spleen colonies (CFU-s) when
      transplanted into lethally irradiated recipients. However, the c-Kit(neg) PHSC
      show delayed or slow reconstitution kinetics when cotransplanted with
      radioprotective bone marrow cells. c-Kit(neg) PHSCs cells can give rise to c
      Kit(pos) cells with CFU-s activity, radioprotective activity, and PHSC activity.
      Thus, constitutive hematopoiesis is maintained by c-Kit(pos) PHSCS cells that are
      recruited from a more primitive quiescent c-Kit(neg) PHSC population, which
      represents a critical developmental stage in definitive hematopoiesis.

PMID- 10072071
TI  - Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is
      characterized by abnormalities in neutrophil function and host defense.
AB  - In mammals, the Rho family GTPase Rac2 is restricted in expression to
      hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were
      created to define the physiological requirement for two near-identical Rac
      proteins in hematopoietic cells. rac2-/- neutrophils displayed significant
      defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the
      endothelial substrate Glycam-1, and in both F-actin generation and p38 and,
      unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants.
      Superoxide production by rac2-/- bone marrow neutrophils was significantly
      reduced compared to wild type, but it was normal in activated peritoneal exudate
      neutrophils. These defects were reflected in vivo by baseline neutrophilia,
      reduced inflammatory peritoneal exudate formation, and increased mortality when
      challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple
      specialized neutrophil functions.

PMID- 10072072
TI  - Cathepsin S required for normal MHC class II peptide loading and germinal center
      development.
AB  - Major histocompatibility complex (MHC) class II molecules acquire antigenic
      peptides after degradation of the invariant chain (Ii), an MHC class II
      associated protein that otherwise blocks peptide binding. Antigen-presenting
      cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10
      kDa fragment, resulting in delayed peptide loading and accumulation of cell
      surface MHC class II/10 kDa Ii complexes. Although cathepsin S-deficient mice
      have normal numbers of B and T cells and normal IgE responses, they show markedly
      impaired antibody class switching to IgG2a and IgG3. These results indicate
      cathepsin S is a major Ii-processing enzyme in splenocytes and dendritic cells.
      Its role in humoral immunity critically depends on how antigens access the immune
      system.

PMID- 10072073
TI  - Impaired invariant chain degradation and antigen presentation and diminished
      collagen-induced arthritis in cathepsin S null mice.
AB  - Cathepsins have been implicated in the degradation of proteins destined for the
      MHC class II processing pathway and in the proteolytic removal of invariant chain
      (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal
      cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii
      degradation in professional APC in vivo. A marked variation in the generation of
      MHC class II-bound Ii fragments and presentation of exogenous proteins was
      observed between B cells, dendritic cells, and macrophages lacking catS. CatS
      deficient mice showed diminished susceptibility to collagen-induced arthritis,
      suggesting a potential therapeutic target for regulation of immune
      responsiveness.

PMID- 10072074
TI  - T cell receptor and coreceptor CD8 alphaalpha bind peptide-MHC independently and
      with distinct kinetics.
AB  - The T cell surface glycoprotein CD8 enhances T cell antigen recognition by
      binding to MHC class I molecules. We show that human CD8 alphaalpha binds to the
      MHC class I molecule HLA-A2 with an extremely low affinity (Kd approximately 0.2
      mM at 37 degrees C) and with kinetics that are between 2 and 3 orders of
      magnitude faster than reported for T cell receptor/peptide-MHC interactions.
      Furthermore, CD8 alphaalpha had no detectable effect on a T cell receptor (TCR)
      binding to the same peptide-MHC class I complex. These binding properties provide
      an explanation as to why the CD8/MHC class I interaction is unable to initiate
      cell-cell adhesion and how it can enhance TCR recognition without interfering
      with its specificity.

PMID- 10072075
TI  - Qualitative and quantitative differences in T cell receptor binding of agonist
      and antagonist ligands.
AB  - The kinetics of interaction between TCR and MHC-peptide show a general
      relationship between affinity and the biological response, but the reported
      kinetic differences between antigenic and antagonistic peptides are very small.
      Here, we show a remarkable difference in the kinetics of TCR interactions with
      strong agonist ligands at 37 degrees C compared to 25 degrees C. This difference
      is not seen with antagonist/positive selecting ligands. The interaction at 37
      degrees C shows biphasic binding kinetics best described by a model of TCR
      dimerization. The altered kinetics greatly increase the stability of complexes
      with agonist ligands, accounting for the large differences in biological response
      compared to other ligands. Thus, there may be an allosteric, as well as a
      kinetic, component to the discrimination between agonists and antagonists.

PMID- 10072076
TI  - Antigen-stimulated dissociation of BCR mIg from Ig-alpha/Ig-beta: implications
      for receptor desensitization.
AB  - B cell antigen receptor (BCR) ligation leads to receptor desensitization wherein
      BCR remain competent to bind antigen and yet fail to transduce signals.
      Desensitized BCR exhibit a defect at the most proximal level of signal
      transduction, consistent with failed transmission of signals through the receptor
      complex. We report that antigen stimulation leads to dissociation or
      destabilization of the BCR reflected by inability to coimmunoprecipitate Ig
      alpha/Ig-beta with mIg. This destabilization is temporally correlated with
      desensitization and occurs in BCR containing mIgM and mIgD. Induction of BCR
      destabilization requires tyrosine kinase activation but is not induced by
      phosphatase inhibitors. BCR destabilization occurs at the cell surface and
      "dissociated" Ig-alpha/Ig-beta complexes remain responsive to anti-Ig-beta
      stimulation, suggesting that mIg-transducer uncoupling may mediate receptor
      desensitization.

PMID- 10072077
TI  - Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells.
AB  - Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice
      deficient in both genes lack all growth hormone and prolactin functions but
      retain functions associated with cytokines such as erythropoietin. Here, we
      demonstrate that, while lymphoid development is normal, Stat5a/b mutant
      peripheral T cells are profoundly deficient in proliferation and fail to undergo
      cell cycle progression or to express genes controlling cell cycle progression. In
      addition, the mice lack NK cells, develop splenomegaly, and have T cells with an
      activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice.
      These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results
      demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2
      signaling in T cells.

PMID- 10072078
TI  - Alternative polyadenylation events contribute to the induction of NF-ATc in
      effector T cells.
AB  - The transcription factor NF-ATc is synthesized in three prominent isoforms. These
      differ in the length of their C terminal peptides and mode of synthesis. Due to a
      switch from the use of a 3' polyA site to a more proximal polyA site, NF-ATc
      expression switches from the synthesis of the two longer isoforms in naive T
      cells to that of short isoform A in T effector cells. The relative low binding
      affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems
      to contribute to its neglect in naive T cells. These alternative polyadenylation
      events ensure the rapid accumulation of high concentrations of NF-ATc necessary
      to exceed critical threshold levels of NF-ATc for gene induction in effector T
      cells.

PMID- 10072079
TI  - The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB
      acting through the NF-kappaB-inducing kinase and IkappaB kinases.
AB  - The proto-oncogene Cot/Tpl-2 encodes a MAP3K-related serine-threonine kinase.
      Expression of wild type Cot activates the IkappaB kinases (IKK) leading to
      induction of NF-kappaB. Conversely, expression of kinase-deficient Cot inhibits
      CD3/CD28 but not TNF alpha induction of NF-kappaB. These findings suggest the
      selective involvement of Cot/Tpl-2 or a closely related kinase in the CD3/CD28
      costimulatory pathway leading to induced nuclear expression of NF-kappaB. In
      contrast, a kinase-deficient mutant of the NF-kappaB-inducing kinase (NIK)
      inhibits both CD3/CD28 and TNF alpha signaling, indicating that these pathways
      converge at or prior to the action of NIK. Consistent with such a sequential
      function of these two kinases, Cot physically assembles with and phosphorylates
      NIK in vivo.

PMID- 10072080
TI  - A sticker-based model for DNA computation.
AB  - We introduce a new model of molecular computation that we call the sticker model.
      Like many previous proposals it makes use of DNA strands as the physical
      substrate in which information is represented and of separation by hybridization
      as a central mechanism. However, unlike previous models, the stickers model has a
      random access memory that requires no strand extension and uses no enzymes; also
      (at least in theory), its materials are reusable. The paper describes computation
      under the stickers model and discusses possible means for physically implementing
      each operation. Finally, we go on to propose a specific machine architecture for
      implementing the stickers model as a microprocessor-controlled parallel robotic
      workstation. In the course of this development a number of previous general
      concerns about molecular computation (Smith, 1996; Hartmanis, 1995; Linial et
      al., 1995) are addressed. First, it is clear that general-purpose algorithms can
      be implemented by DNA-based computers, potentially solving a wide class of search
      problems. Second, we find that there are challenging problems, for which only
      modest volumes of DNA should suffice. Third, we demonstrate that the formation
      and breaking of covalent bonds is not intrinsic to DNA-based computation. Fourth,
      we show that a single essential biotechnology, sequence-specific separation,
      suffices for constructing a general-purpose molecular computer. Concerns about
      errors in this separation operation and means to reduce them are addressed
      elsewhere (Karp et al., 1995; Roweis and Winfree, 1999). Despite these
      encouraging theoretical advances, we emphasize that substantial engineering
      challenges remain at almost all stages and that the ultimate success or failure
      of DNA computing will certainly depend on whether these challenges can be met in
      laboratory investigations.

PMID- 10072081
TI  - A method for biomolecular structural recognition and docking allowing
      conformational flexibility.
AB  - In this work, we present an algorithm developed to handle biomolecular structural
      recognition problems, as part of an interdisciplinary research endeavor of the
      Computer Vision and Molecular Biology fields. A key problem in rational drug
      design and in biomolecular structural recognition is the generation of binding
      modes between two molecules, also known as molecular docking. Geometrical fitness
      is a necessary condition for molecular interaction. Hence, docking a ligand
      (e.g., a drug molecule or a protein molecule), to a protein receptor (e.g.,
      enzyme), involves recognition of molecular surfaces. Conformational transitions
      by "hinge-bending" involves rotational movements of relatively rigid parts with
      respect to each other. The generation of docked binding modes between two
      associating molecules depends on their three dimensional structures (3-D) and
      their conformational flexibility. In comparison to the particular case of rigid
      body docking, the computational difficulty grows considerably when taking into
      account the additional degrees of freedom intrinsic to the flexible molecular
      docking problem. Previous docking techniques have enabled hinge movements only
      within small ligands. Partial flexibility in the receptor molecule is enabled by
      a few techniques. Hinge-bending motions of protein receptors domains are not
      addressed by these methods, although these types of transitions are significant,
      e.g., in enzymes activity. Our approach allows hinge induced motions to exist in
      either the receptor or the ligand molecules of diverse sizes. We allow
      domains/subdomains/group of atoms movements in either of the associating
      molecules. We achieve this by adapting a technique developed in Computer Vision
      and Robotics for the efficient recognition of partially occluded articulated
      objects. These types of objects consist of rigid parts which are connected by
      rotary joints (hinges). Our method is based on an extension and generalization of
      the Hough transform and the Geometric Hashing paradigms for rigid object
      recognition. We show experimental results obtained by the successful application
      of the algorithm to cases of bound and unbound molecular complexes, yielding fast
      matching times. While the "correct" molecular conformations of the known
      complexes are obtained with small RMS distances, additional, predictive good
      fitting binding modes are generated as well. We conclude by discussing the
      algorithm's implications and extensions, as well as its application to
      investigations of protein structures in Molecular Biology and recognition
      problems in Computer Vision.

PMID- 10072082
TI  - Torsional relaxation for biopolymers.
AB  - We describe a method for making natural, physical movements in a chained polymer
      by sequentially adjusting a few neighboring torsion angles in the polymer
      backbone. In addition to being very fast and easy to implement, the method is
      also very general. It applies equally well to proteins and nucleic acids. This
      method is then used to design a local refinement procedure. We test the
      refinement procedure on the minimization of a simple energy function for
      proteins. The energy function has a simplified potential for hydrophobic
      interaction, a hydrogen-bond term, and a term for van der Waals interaction.
      There is considerable current interest in such simple energy functions for
      protein folding. When applied to refine structures found by a global search
      method, the refinement is able to produce large reduction in the hydrogen-bond
      term and the van der Waal term of the energy. We conclude that the method is
      particularly effective in finding good "packing" of residues in an initially
      compact conformation.

PMID- 10072083
TI  - A decision tree system for finding genes in DNA.
AB  - MORGAN is an integrated system for finding genes in vertebrate DNA sequences.
      MORGAN uses a variety of techniques to accomplish this task, the most distinctive
      of which is a decision tree classifier. The decision tree system is combined with
      new methods for identifying start codons, donor sites, and acceptor sites, and
      these are brought together in a frame-sensitive dynamic programming algorithm
      that finds the optimal segmentation of a DNA sequence into coding and noncoding
      regions (exons and introns). The optimal segmentation is dependent on a separate
      scoring function that takes a subsequence and assigns to it a score reflecting
      the probability that the sequence is an exon. The scoring functions in MORGAN are
      sets of decision trees that are combined to give a probability estimate.
      Experimental results on a database of 570 vertebrate DNA sequences show that
      MORGAN has excellent performance by many different measures. On a separate test
      set, it achieves an overall accuracy of 95 %, with a correlation coefficient of
      0.78, and a sensitivity and specificity for coding bases of 83 % and 79%. In
      addition, MORGAN identifies 58% of coding exons exactly; i.e., both the beginning
      and end of the coding regions are predicted correctly. This paper describes the
      MORGAN system, including its decision tree routines and the algorithms for site
      recognition, and its performance on a benchmark database of vertebrate DNA.

PMID- 10072084
TI  - Assembling genes from predicted exons in linear time with dynamic programming.
AB  - In a number of programs for gene structure prediction in higher eukaryotic
      genomic sequences, exon prediction is decoupled from gene assembly: a large pool
      of candidate exons is predicted and scored from features located in the query DNA
      sequence, and candidate genes are assembled from such a pool as sequences of
      nonoverlapping frame-compatible exons. Genes are scored as a function of the
      scores of the assembled exons, and the highest scoring candidate gene is assumed
      to be the most likely gene encoded by the query DNA sequence. Considering
      additive gene scoring functions, currently available algorithms to determine such
      a highest scoring candidate gene run in time proportional to the square of the
      number of predicted exons. Here, we present an algorithm whose running time grows
      only linearly with the size of the set of predicted exons. Polynomial algorithms
      rely on the fact that, while scanning the set of predicted exons, the highest
      scoring gene ending in a given exon can be obtained by appending the exon to the
      highest scoring among the highest scoring genes ending at each compatible
      preceding exon. The algorithm here relies on the simple fact that such highest
      scoring gene can be stored and updated. This requires scanning the set of
      predicted exons simultaneously by increasing acceptor and donor position. On the
      other hand, the algorithm described here does not assume an underlying gene
      structure model. Indeed, the definition of valid gene structures is externally
      defined in the so-called Gene Model. The Gene Model specifies simply which gene
      features are allowed immediately upstream which other gene features in valid gene
      structures. This allows for great flexibility in formulating the gene
      identification problem. In particular it allows for multiple-gene two-strand
      predictions and for considering gene features other than coding exons (such as
      promoter elements) in valid gene structures.

PMID- 10072085
TI  - Iterative stepwise discriminant analysis: a meta-algorithm for detecting
      quantitative sequence motifs.
AB  - An algorithm is presented for detecting a quantitative pattern in peptide
      fragments that bind class II major histocompatibility complex (MHC) molecules. It
      is referred to as a meta-algorithm because it requires successive applications of
      Stepwise Discriminate Analysis (SDA). On every iteration the best subsequence
      candidates are selected from sequences known to bind class II MHC molecules. When
      SDA compares probable binding subsequences with subsequences known not to bind
      class II MHC molecules, a quantitative model emerges that is capable of
      classifying subsequences as binding or non-binding. In an iterative manner, the
      resultant model is utilized as a criterion for selecting probable binding
      subsequence candidates. The procedure is repeated until models converge. In the
      illustrated examples, the final models correctly classify over 95% of the
      peptides in a database of peptides whose binding affinity for HLA-DR1 is known.
      The final model can then be used to predict the binding affinity of peptides that
      have not yet been laboratory tested.

PMID- 10072086
TI  - Constructing and counting phylogenetic invariants.
AB  - The method of invariants is an approach to the problem of reconstructing the
      phylogenetic tree of a collection of m taxa using nucleotide sequence data.
      Models for the respective probabilities of the 4m possible vectors of bases at a
      given site will have unknown parameters that describe the random mechanism by
      which substitution occurs along the branches of a putative phylogenetic tree. An
      invariant is a polynomial in these probabilities that, for a given phylogeny, is
      zero for all choices of the substitution mechanism parameters. If the invariant
      is typically non-zero for another phylogenetic tree, then estimates of the
      invariant can be used as evidence to support one phylogeny over another. Previous
      work of Evans and Speed showed that, for certain commonly used substitution
      models, the problem of finding a minimal generating set for the ideal of
      invariants can be reduced to the linear algebra problem of finding a basis for a
      certain lattice (that is, a free Z-module). They also conjectured that the
      cardinality of such a generating set can be computed using a simple "degrees of
      freedom" formula. We verify this conjecture. Along the way, we explain in detail
      how the observations of Evans and Speed lead to a simple, computationally
      feasible algorithm for constructing a minimal generating set.

PMID- 10072087
TI  - A uniform framework for ordered restriction map problems.
AB  - Optical Mapping is an emerging technology for constructing ordered restriction
      maps of DNA molecules. The underlying computational problems for this technology
      have been studied and several models have been proposed in recent literature.
      Most of these propose combinatorial models; some of them also present statistical
      approaches. However, it is not a priori clear as to how these models relate to
      one another and to the underlying problem. We present a uniform framework for the
      restriction map problems where each of these various models is a specific
      instance of the basic framework. We achieve this by identifying two "signature"
      functions f() and g() that characterize the models. We identify the constraints
      these two functions must satisfy, thus opening up the possibility of exploring
      other plausible models. We show that for all of the combinatorial models proposed
      in literature, the signature functions are semi-algebraic. We also analyze a
      proposed statistical method in this framework and show that the signature
      functions are transcendental for this model. We also believe that this framework
      would provide useful guidelines for dealing with other inferencing problems
      arising in practice. Finally, we indicate the open problems by including a survey
      of the best known results for these problems.

PMID- 10072088
TI  - An easy case of sorting by reversals.
AB  - We show that a special case of sorting by reversals can be performed in
      polynomial time, namely, when the number of breakpoints is twice the distance.

PMID- 10072089
TI  - A database for cell signaling networks.
AB  - We developed a data and knowledge base for cellular signal transduction in human
      cells, to make this rapidly growing information available. The database includes
      all the biological properties of cellular signal transduction, including
      biological reactions that transfer cellular signals and molecular attributes
      characterized by sequences, structures, and functions. Since the database is
      based on the object-oriented technique, highly flexible methods of data
      definition and modification are necessary to handle this diverse and complex
      biological information. The database includes attractive graphical
      representations of signaling cascades and the three-dimensional structure of
      molecules. The database is a novel application of ACEDB, which was the database
      originally developed to store the C. elegans genome. The database can be accessed
      through the Internet at http://geo.nihs.go.jp/csndb.html.

PMID- 10072090
TI  - Dissociation between force and [Ca2+]i during extra systoles in guinea-pig
      ventricular muscle microinjected with fura-2.
AB  - Thin trabeculae were dissected from the right ventricle of guinea-pig heart and
      stimulated to contract isometrically at 0.5 Hz (26 degrees C). Rapid and
      transient changes of force were obtained by inducing three extra systoles (ES1-3)
      at 450-ms intervals. The two regular contractions (P1-2) following (ES1-3) were
      potentiated. Fura-2 salt was microinjected into the preparation to monitor
      intracellular calcium ([Ca2+]i). Three distinct phases of [Ca2+]i were seen: (1)
      a rapid rising phase to about 200 nmol L(-1), (2) a slower rising phase to a peak
      at 400 nmol L(-1), and (3) a slow decline to about 50 nmol L(-1). During ES1,
      there was a discrepancy between force, which decreased, and peak [Ca2+]i, which
      increased to 600 nmol L(-1). It is likely that the increased [Ca2+]i during the
      extra systoles reflects increased sarcolemmal calcium inflow, causing post-extra
      systolic potentiation. Ryanodine (1-2 microM) was added to inhibit the
      intracellular calcium release and thus reduce the intracellular [Ca2+]i gradients
      following excitation. Ryanodine inhibited phase 1 of [Ca2+]i and abolished post
      extra-systolic potentiation. There was a close relationship between dF/dt and
      [Ca2+]i with ryanodine during control and ES1-3. It is likely that fura-2 reports
      a spatially averaged [Ca2+]i and that phase 1 of the signal therefore apparently
      underestimates activator calcium in the close vicinity of the contractile
      elements.

PMID- 10072091
TI  - Endogenous muscarinic activity attenuates adrenergic inotropic effects in field
      stimulated atrial myocardium from children with congenital heart defects.
AB  - To analyse the possible influence of endogenous muscarinic activity on the
      inotropic effects of endogenously released noradrenaline in field stimulated
      myocardial preparations from atria of children with congenital heart defects, we
      studied the maximal effect of the muscarinic antagonist atropine (1.5 micromol L(
      1)). Maximal force of contraction increased by 12.8 +/- 2.0% (SEM), while the
      maximal rate of development of the force increased by 16.7 +/- 2.7% (SEM). Time
      to half maximal developed force was 57 +/- 5 s (SEM). Time to peak force, time to
      relax to the 20% level and relaxation time all decreased significantly after
      atropine. Compared with endogenous adrenoceptor stimulation alone, the combined
      effects of partial muscarinic and adrenergic receptor stimulation thus were
      moderate reductions of the maximal force of contraction and maximal rate of
      development of the force and increased time to peak force, time to relax to the
      20% level and relaxation time. The main effect of the endogenous muscarinic
      activity probably was to attenuate the effect of the beta-adrenoceptor
      stimulation. The endogenous muscarinic activity in field stimulated atrial
      preparations from children is significant, and has to be taken into account in
      experimental set-ups.

PMID- 10072092
TI  - Dilatory responses to acetylcholine, calcitonin gene-related peptide and
      substance P in the congestive heart failure rat.
AB  - It was examined to what extent congestive heart failure (CHF) in rats, induced by
      ligation of the left coronary artery, affects the vascular responses to the
      vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide
      (CGRP), and substance P (SP). After induction of CHF status, the basilar,
      mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory
      responses were determined in relation to pre-contraction by the thromboxane
      mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced
      stronger contraction in CHF basilar and renal arteries compared with the
      corresponding segments in Sham. ACh induced concentration-dependent dilations in
      all vessels examined with no difference of maximum relaxation or potency between
      CHF and Sham. SP induced weak dilations in all arteries examined while the
      response was markedly attenuated in CHF iliac veins compared with Sham (Emax%
      12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF
      basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and
      less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham.
      Further, CGRP was less potent in the renal artery of CHF rats compared with Sham
      (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was
      more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It
      can be concluded CHF is accompanied by alterations in the vascular response to
      the dilatory substances studied. The changes differ between vascular beds and
      between the different substances.

PMID- 10072093
TI  - Neurohumoral responses to a single haemodialysis in chronic renal patients.
AB  - The effect of volume reduction on vasoactive substances and their role in
      estimating dry weight in haemodialysis patients was studied. Plasma atrial
      natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity
      and serum aldosterone were measured in 12 patients before and after bicarbonate
      haemodialysis. Haemodynamical changes were registered and cardiac function and
      diameter of the inferior vena cava were measured by echocardiography before and
      after dialysis. Plasma concentration of ANP was significantly reduced by
      haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas
      concentrations of the other hormones were unchanged. The change in the
      concentration of ANP did not have significant correlation with weight reduction.
      The concentration of ANP correlated positively with the diameter of the inferior
      vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The
      concentration of ANP before or after haemodialysis or its change during dialysis
      did not correlate with any other biochemical parameter. The results show that
      plasma ANP level is decreased after volume reduction in patients with chronic
      renal failure, whereas other hormonal systems are unresponsive. However, plasma
      concentration of ANP seems to have no role in estimating dry weight in chronic
      haemodialysis patients.

PMID- 10072094
TI  - Specific blood flow reducing effects of hyperoxaemia on high flow capillaries in
      the pig brain.
AB  - The mechanisms behind oxygen mediated changes in tissue blood flow remain
      unsettled. Today these are thought to (from experiments on separate vessels and
      other tissues than the brain) operate through the vessels themselves, probably by
      involvement of the endothelium in the distal parts of the vascular tree. The aim
      of this study was to investigate how hyperoxaemia affects the cerebrocortical
      capillary blood flow distribution in order to gain further knowledge of oxygen
      mediated blood flow regulating mechanisms. The experiments were performed on
      seven ventilated anaesthetized pigs. A multiwire Clark-type microelectrode,
      placed on the brain surface (motor cortex), was used for capillary blood flow
      (hydrogen clearance) and oxygen pressure measurements, both of which were made at
      normoxaemia (arterial PO2 14.4 kPa) and hyperoxaemia (arterial PO2 50.4 kPa)(the
      animals serving as their own control). Blood pressure, arterial PCO2 and pH
      remained unchanged throughout the experiments. During hyperoxaemia a 11%
      reduction in the cerebrocortical capillary blood flow was found (P < 0.001). This
      flow reduction was seen mainly in two capillary blood flow classes (6/7 animals).
      In parallel a heterogeneous increase in the cerebrocortical oxygen pressures from
      4.5 to 10.1 kPa (mean) (P < 0.001) was found. These results show that
      hyperoxaemia causes a selective reduction in capillary blood flow affecting
      capillaries at specific flow levels. A finding that suggests, for the brain, that
      both the oxygen sensor and effect mechanism is situated distally, in the vascular
      tree.

PMID- 10072095
TI  - C-peptide potentiates the vasoconstrictor effect of neuropeptide Y in insulin
      dependent diabetic patients.
AB  - Recent findings suggest that proinsulin C-peptide improves renal and nerve
      function as well as microcirculation in patients with insulin-dependent diabetes
      possibly by stimulating Na-K+-ATPase activity. Furthermore, in vitro studies on
      proximal rat renal tubule cells show that the effect of C-peptide on Na+, K+
      ATPase activity is potentiated in the presence of the vasoconstrictor peptide
      neuropeptide Y. The aim of the present study was to examine whether the effects
      of neuropeptide Y on resting forearm blood flow in insulin-dependent patients is
      altered in the presence of C-peptide. Forearm blood flow was measured by a
      plethysmographic method in eight insulin-dependent patients and six healthy
      control subjects. Neuropeptide Y (20, 200 and 2000 pmol min(-1)) was infused into
      the brachial artery before and during an i.v. infusion of C-peptide (5 pmol kg(
      1) min(-1)). Basal blood flow was 36.7 +/- 2.2 mL min(-1) L(-1) tissue. It
      decreased in a dose dependent manner by 11 +/- 2, 18 +/- 3 and 25 +/- 3%,
      respectively, during infusion of neuropeptide Y. Administration of C-peptide
      increased basal blood flow by 25 +/- 6%, to 46.3 +/- 3.5 mL min(-1) L(-1) tissue
      (P < 0.01) and forearm glucose uptake by 76 +/- 34% (P < 0.05). Infusion of the
      three doses of neuropeptide Y during administration of C-peptide decreased
      forearm blood flow by 14 +/- 4, 22 +/- 3 and 42 +/- 4%. There was a significant
      difference (43%, P < 0.001) between the reduction in blood flow evoked by the
      high dose (2000 pmol min(-1)) of neuropeptide Y before and during C-peptide
      infusion. Similar differences were also obtained when data were calculated as
      changes in vascular resistance. C-peptide did not affect resting forearm blood
      flow or the response to neuropeptide Y in healthy controls. In conclusion, the
      present data demonstrate that C-peptide increases resting forearm blood flow and
      augments the vasoconstrictor effects of neuropeptide Y in insulin-dependent
      patients.

PMID- 10072096
TI  - Effects of exhaustive exercise on biochemical characteristics of sarcoplasmic
      reticulum from rat soleus muscle.
AB  - This study examined the effects of acute high-intensity and moderate-intensity
      exercise on Ca2+-stimulated adenosine triphosphatase (ATPase) activity and the
      Ca2+ and ATP dependence of Ca2+-ATPase of the sarcoplasmic reticulum (SR) in the
      soleus muscle. The rats were run on 10% grade at 50 m min(-1) or 25 m min(-1)
      until fatigued (avg. time to exhaustion 2.8 and 87.7 min, respectively). The
      catalytic activities of SR Ca2+-ATPase were significantly depressed immediately
      after both types of exercise. Kinetic analyses demonstrated that the Ca2+
      affinity of Ca2+-ATPase was elevated by both types of exercise adopted in the
      present investigation whereas the increase in the ATP affinity was brought about
      by only high-intensity exercise. These results suggest that exhaustive exercise
      may induce in slow-twitch muscle fibre the environmental changes, which adversely
      affect SR Ca2+-ATPase activity and can overcome the positive influence arising
      from the increase in the Ca2+ and/or ATP affinities of SR Ca2+-ATPase.

PMID- 10072097
TI  - Responses of total and free insulin-like growth factor-I and insulin-like growth
      factor binding protein-3 after resistance exercise and training in elderly
      subjects.
AB  - To investigate the effects of an acute bout of exercise on total and free insulin
      like growth factor-I and insulin-like growth factor binding protein-3 plasma
      concentrations, 32 healthy elderly subjects (67-80 years, 16 men) performed a
      strength test, which consisted of two sets of 12 repetitions at 12-repetition
      maximum and four sets of 5 repetitions at 5-repetition maximum for horizontal leg
      press, seated chest press, and bilateral leg extension movements. Ten out of the
      32 subjects served as time controls. Blood samples were drawn prior (08.30 h),
      immediately (10.30 h), and 6 h (16.30 hours) after the strength test in
      exercising and resting subjects. The 32 subjects were then randomly assigned to
      habitual physical activity or to an 8-week strength training program. After 8
      weeks, both sedentary and trained groups underwent blood samplings under the
      above-mentioned conditions. The exercising group showed increased total and free
      insulin-like growth factor-I concentrations immediately (+17.7 and +93.8%,
      respectively), and 6 h (+7.5 and +31.2%, respectively) after the test, whereas no
      significant changes in insulin-like growth factor binding protein-3
      concentrations were observed in either exercising or resting control groups.
      Strength training induced no significant changes in baseline insulin-like growth
      factor-I and insulin-like growth factor binding protein-3 concentrations. Trained
      and sedentary groups showed similar hormonal response pattern to the strength
      test, which consisted of increased total and free insulin-like growth factor-I
      concentrations. The data indicated that strength exercise can induce an early and
      sustained insulin-like growth factor-I release, in elderly subjects, regardless
      of their training status.

PMID- 10072098
TI  - Gender differences in skeletal muscle fibre damage after eccentrically biased
      downhill running in rats.
AB  - Specific antibodies against structural proteins of muscle fibres (actin, desmin,
      dystrophin) and extracellular matrix (fibronectin) were used to study the effect
      of eccentrically biased downhill running exercise (13,5 degrees, 17 m min(-1),
      130 min) on the magnitude and properties of myofibre injury in the quadriceps
      femoris muscle of male and female rats. Muscle beta-glucuronidase activity, a
      quantitative indicator of muscle damage, showed clearly smaller increase in
      female than in male rats during the 4-day period following exercise. A similar
      course of histopathological changes was observed in both sexes, although females
      showed slower and less marked changes than males. In males, discontinuous or even
      lost submembrane protein dystrophin staining was observed in some swollen fibres
      immediately after exercise, before the loss of desmin and staining of
      disorganized actin, i.e. before the disruption of the cytoskeletal system and the
      contractile apparatus. The observation that no dramatic changes in the
      microarchitecture of the muscle fibres were detected immediately or even 6 h
      after the exercise in females compared with males may indicate that the
      sarcolemma of the females might be strengthened against membrane damage by a
      still unknown stabilizing compound.

PMID- 10072099
TI  - Oxidative stress and haematological changes in immobilized rats.
AB  - Immobilization stress induces formation of reactive oxygen species (ROS) and
      leads to the oxidative injury in various tissues. In this study, the effects of
      immobilization stress on peripheral blood cells distribution, plasma level of
      thiobarbituric acid reactive substances (TBARS), and activities of antioxidant
      enzymes in erythrocytes were investigated in male Fischer rats. A significant
      increase in plasma TBARS was observed during and after the stress. Dramatic
      increases of neutrophils and monocytes imply that ROS formation resulted from
      their activation. Furthermore, the antioxidant activities of catalase and
      superoxide dismutase (SOD) in erythrocytes were dramatically increased during and
      after the stress, while a large fall in erythrocyte number was observed. These
      findings suggest that the activation of immune cells can be a source of the
      immobilization-induced ROS production, and that antioxidant enzymes in
      erythrocytes play an important role in preventing the ROS-induced injuries.

PMID- 10072100
TI  - Attenuating the decline in ATP arrests the exercise training-induced increases in
      muscle GLUT4 protein and citrate synthase activity.
AB  - Thirty-two female Sprague-Dawley rats were assigned to one of four groups:
      control (CON); exercise training (TR); exercise training + clenbuterol treatment
      (0.8 mg kg body wt(-1) d(-1)) (TR + CL) or exercise training + clenbuterol
      treatment + 2% beta-guanidinoproprionic acid diet (TR + CL + beta) to examine
      whether alterations in the high energy phosphate state of the muscle mediates
      exercise training-induced increases in skeletal muscle GLUT4 protein
      concentration and citrate synthase activity. Exercise training consisted of
      running the rats 5 d week(-1) for 8 weeks on a motor-driven treadmill (32 m min(
      1), 15% grade). Gastrocnemius GLUT4 protein concentration and citrate synthase
      activity were significantly elevated in the TR animals, but these adaptations
      were attenuated in the TR + CL animals. Providing beta-GPA in combination with
      clenbuterol enabled training to elevate GLUT4 protein concentration and citrate
      synthase activity, with the increase in GLUT4 being greater than that observed
      for the TR animals. Skeletal muscle ATP levels were reduced in the TR + CL + beta
      animals while ATP levels in the TR + CL animals were significantly elevated
      compared with CON. An acute 40-min bout of electrical stimulation of the sciatic
      nerve was found to lower skeletal muscle ATP levels by approximately 50% and
      elevate cAMP levels in all groups. No difference in post-contraction cAMP levels
      were observed among groups. However, post-contraction ATP levels in the TR + CL
      animals were significantly greater than the other groups. Collectively, these
      findings suggest that exercise training-induced increases in skeletal muscle
      GLUT4 protein concentration and citrate synthase activity are initiated in
      response to a reduction in the skeletal muscle ATP concentration.

PMID- 10072101
TI  - Physiological oxygen concentration gives an oscillating spontaneous tone in
      guinea-pig tracheal preparations.
AB  - The spontaneous tone in isolated six-segment preparations of guinea-pig trachea
      was examined. In 12% oxygen (corresponding to normal systemic arterial oxygen
      pressure) the preparations developed a spontaneous tone with regular oscillations
      (6.6 min(-1)), usually grouped in so-called complexes (7.5 h(-1)). The average
      tone during an entire complex amounted to 12% of a maximum KCl-induced
      contraction. The complex tone was highly stable during observation periods of at
      least 4 h, and was reversibly transformed to the 'classical', smooth type when
      exposed to 94% oxygen. Stretch of preparations in low oxygen resulted in a fast,
      stable change of tone, while preparations in traditionally high oxygen reacted
      slower, and lost 40% of the active tension during the hour following stretch.
      Indomethacin (10 microM) did not eliminate the oscillating behaviour, but reduced
      the average size of the tone by 44%. Exposure to the C-fibre blocking agent
      capsaicin (50 microM) and the local anaesthetic lidocaine (1 mM) completely
      eliminated the oscillations and complexes, although the preparations retained a
      smooth tone. Atropine, propranolol and tetrodotoxin did not affect the complex
      tone. This study demonstrates for the first time that guinea-pig tracheal
      preparations that are exposed to near-physiological oxygen concentrations develop
      a new type of oscillating spontaneous tone, which is largely prostaglandin
      independent, but appears to require transmitter release from sensory C-fibres. We
      argue that the complex tone is physiological, and that traditionally high oxygen
      (95%) probably results in non-physiological hyperoxic changes in this
      preparation.

PMID- 10072102
TI  - Effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP) and
      vasoactive intestinal polypeptide (VIP) on chloride in HT29 cells studied by X
      ray microanalysis.
AB  - The colon cancer cell line HT29 is a useful model to study intestinal chloride
      secretion. These cells have both cAMP-activated and calcium-activated chloride
      channels. Changes in elemental content of the cells after stimulation with
      agonists were determined by X-ray microanalysis in the scanning or scanning
      transmission electron microscope. Exposure of HT29 cells to pituitary adenylate
      cyclase activating polypeptide-27 (PACAP) caused a transient decrease in the
      cellular Cl and K concentrations, indicating (net) efflux of chloride. The effect
      of PACAP is inhibited by somatostatin, which is known to inhibit cAMP-activated
      as well as calcium-activated chloride secretion and by U-73122, an inhibitor of
      phospholipase C. Alloxan, an inhibitor of adenylate cyclase, did not
      significantly affect the PACAP-induced loss of chloride. The calcium-chelating
      agent EGTA inhibited the PACAP-induced loss of chloride, indicating the need for
      extracellular calcium ions. Also vasointestinal polypeptide (VIP) caused a
      decrease of the cellular chloride concentration in HT29 cells. VIP-induced loss
      of chloride could be inhibited by pre-treating the cells with somatostatin or
      UK14,304, an alpha-2 adrenergic agonist that has been shown previously to inhibit
      purinergically activated chloride efflux. Our results indicate that there is
      cross-talk between the cAMP- and the calcium-activated pathways for chloride
      secretion in HT29 cells.

PMID- 10072103
TI  - Mechanisms of impaired urinary concentrating ability in adult rats treated
      neonatally with enalapril.
AB  - Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1
      receptor blockade induces irreversible renal histological abnormalities and an
      impaired urinary concentrating ability in the rat. The aim of the present study
      was to determine the pathophysiological mechanisms underlying the defect in urine
      concentration in adult rats treated neonatally with enalapril. Male Wistar rats
      received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline
      vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine
      osmolality (Uosm(max)), renal function and tubular free water reabsorption
      (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations,
      renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12
      16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05)
      and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after
      administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril
      treated rats showed marked papillary atrophy, a decrease in medullary tissue
      solute concentrations, and a reduction in AQP2 expression specifically in the
      inner medulla. Glomerular filtration rate, renal plasma flow and urinary
      excretion rates of sodium, potassium and chloride did not differ between groups.
      In conclusion, adult rats treated neonatally with enalapril showed a urinary
      concentrating defect of renal origin which primarily could be explained by the
      papillary atrophy. However, an impaired ability to generate medullary
      interstitial hypertonicity, and a decrease in inner medullary AQP2 expression,
      also seem to contribute to this defect.

PMID- 10072104
TI  - pH after competitive rowing: the lower physiological range?

PMID- 10072105
TI  - Renomedullary interstitial cells regulate hyaluronan turnover depending on growth
      media osmolality suggesting a role in renal water handling.

PMID- 10072106
TI  - Decreased plasma tissue factor pathway inhibitor in women taking combined oral
      contraceptives.
AB  - Use of combined oral contraceptives (OC) is associated with a significant risk of
      thrombosis. The mechanisms of this effect are not clearly defined. Tissue factor
      pathway inhibitor (TFPI) is a circulating anti-coagulant that inhibits the
      earliest steps in activation of the extrinsic coagulation pathway. It plays a
      central role in control of coagulation but its contribution to the thrombotic
      risk associated with OC has not been assessed. Plasma TFPI antigen and activity,
      factor VIIa, prothrombin fragments 1&2, von Willebrand antigen, fibrinogen, and
      low density lipoprotein cholesterol were measured by standard assays in women
      taking OC (aged 16 to 45 years, n = 40) and age-matched women not taking OC
      (controls, n = 40). Plasma TFPI antigen did not vary significantly across the
      menstrual cycle in controls. Women on OC had a 25% reduction in plasma TFPI
      antigen (median 51.0 ng/ml; 95% confidence intervals [CI] 37.5 to 85.5; control
      68.0 ng/ml, CI 61.0 to 95.0; P < 0.001) and a 29% reduction in TFPI activity
      (78.5 U/ml, CI 57.5 to 107.5; control 111.0 U/ml, CI 79.5 to 171.0; P < 0.001)
      compared to controls. Plasma factor VIIa activity and prothrombin fragments 1&2
      were also significantly increased in women using OC (both P < 0.001), indicating
      activation of the extrinsic coagulation pathway. These results demonstrate that
      normal cyclic variations in estrogen and/or progesterone do not significantly
      alter plasma TFPI levels. However, estrogens and/or progestogens in OC result in
      activation of the extrinsic coagulation pathway and significantly reduce plasma
      TFPI, its major circulating inhibitor. Reduced plasma TFPI levels may underlie
      the thrombotic effects of OC.

PMID- 10072107
TI  - Lack of association between venous thrombosis and subsequent malignancy in a
      retrospective cohort study in young patients.
AB  - Since the publication of Trousseau in 1865, several studies have documented an
      increased incidence of cancer in patients with deep venous thrombosis (DVT)
      especially those with idiopathic or recurrent DVT, but in young patients this
      association is not clear and is therefore a subject of controversy. We performed
      a retrospective study in a consecutive cohort of 40 young patients (age <40
      years) with a DVT and without a known cancer. All patients were diagnosed in our
      hospital during the period of 1988-1992. At the time of diagnosis, a routine
      examination to detect the presence of malignant disease was made. For the follow
      up, all patients included in the study were asked to return to our unit and were
      interviewed for symptoms that could suggest a malignant disease. The mean follow
      up was five years (from three to eight years). Twenty-four patients had DVT in
      the lower limbs and three in the upper extremities, nine had pulmonary embolism
      (six of them with DVT) and four had DVT in other sites. Sixteen patients (40%)
      had secondary DVT due to nonbiological causes, abnormalities in hemostasis were
      found in 14 patients (35%), and biological or environmental triggering factors
      were not identified in 10 patients (25%). Malignancies were not detected at
      diagnosis and in the follow-up. In our experience, venous-thrombotic patients
      under the age of 40 have a low incidence of subsequent cancer. Further studies
      should be performed to confirm this observation and to ascertain whether
      extensive screening for cancer is a cost-effective approach.

PMID- 10072108
TI  - Serum macrophage colony-stimulating factor (M-CSF) level is elevated in patients
      with old cerebral infarction related to vascular damage.
AB  - We measured the serum levels of macrophage colony-stimulating factor (M-CSF) in
      37 patients with an old cerebral infarction who had been surmised to have a
      damaged vessel wall and who had been in a stable condition for over three months
      after stroke onset, and those of 41 healthy control subjects. The M-CSF levels in
      the patients were significantly higher (P < 0.01) than those of the controls at
      1320.4 +/- 410.6 unit/ml and 853.9 +/- 180.3 unit/ml, respectively. The plasma
      levels of von Willebrand factor (vWF) antigen (P < 0.01) and thrombomodulin (TM)
      (P < 0.05), as well as those of thrombin-antithrombin III (TAT) complex (P <
      0.05), prothrombin fragment 1+2 (F1+2) (P < 0.02), D-dimer products of
      crosslinked fibrin degradation products (D-dimer) (P < 0.01), and plasmin
      antiplasmin (PAP) complex (P < 0.05) in the patients were also significantly
      higher than those in the controls. Significant positive correlations (P < 0.01)
      were found between these parameters and the M-CSF level, but there was no
      significant correlation between the M-CSF level and the white blood cell count,
      serum lipids, or blood pressure. Based on these results, we suggest that an
      increased M-CSF level indicates vascular damage or a thrombotic state in patients
      with an old cerebral infarction.

PMID- 10072109
TI  - Expression of Bcl-2 by human bone marrow mast cells and its overexpression in
      mast cell leukemia.
AB  - Bcl-2 protein plays a major role in the prevention of programmed cell death of
      differentiating cells. In the present study, the expression of cytoplasmic bcl-2
      by human Bone Marrow Mast Cells (BMMC) from both normal and pathological bone
      marrow samples was examined. A total of 35 subjects corresponding to 9 healthy
      volunteers, 8 cases of adult indolent systemic mast cell disease (SMCD), 4 cases
      of pediatric mastocytosis (PM), 11 cases of hematological malignancies (HM), 2
      cases of reactive bone marrow, and 1 case of mast cell leukemia (MCL) were
      analyzed. The expression of bcl-2 was studied using quantitative three-color flow
      cytometry. We also studied the molecular configuration of the bcl-2 gene and
      other relatives by Southern blot and polymerase chain reaction (PCR) in the MCL
      case. Bcl-2 expression was detected in BMMC from all samples analyzed. No
      significant differences on the expression of bcl-2 were detected between BMMC
      from healthy subjects and patients with SMCD, PM, HM, and reactive bone marrow.
      By contrast, bcl-2 protein was overexpressed in BMMC from MCL patient without
      gene rearrangement. Our results show that bcl-2 protein was constitutively
      expressed by BMMC. BMMC from MCL display overexpression of bcl-2, which could not
      be related to molecular rearrangements involving the bcl-2 gene. The expression
      of this protein by mature MC may play a role in the prevention of MC apoptosis
      and thus help to explain the long survival of these cells. The overexpression of
      bcl-2 by BMMC in MCL may help to explain their resistance to chemotherapy-induced
      apoptosis.

PMID- 10072110
TI  - Study of fibrinolytic parameters in different types of polycythemia.
AB  - Polycythemia vera (PV) is a myeloproliferative disorder characterized by
      thrombotic and, less often, bleeding complications. Many mechanisms have been
      advanced to explain the occurrence of these complications, none of them
      satisfactory. We examined a cohort of 27 patients with PV, secondary
      erythrocytosis, and essential thrombocythemia for coagulation and fibrinolytic
      parameters, including euglobulin lysis test, D-dimer, and alpha2 antiplasmin. Ten
      of the 27 patients developed one or more thrombotic complications during the
      study. We found no clinical correlation between the studied parameters and the
      complications. Three patients, one of each group, with elevated serum alpha2
      antiplasmin levels, developed severe arterial or venous thromboses.

PMID- 10072111
TI  - Myelodysplastic syndromes with nephrotic syndrome.
AB  - It is sometimes reported that the immunological abnormalities in myelodysplastic
      syndromes (MDS) induce autoimmune disease (i.e., acute systemic vasculitic
      syndrome, chronic cutaneous vasculitis, polyneuropathy, relapsing polychondritis,
      and steroid-responsive pulmonary disorders). We investigated the clinical
      features of patients with MDS accompanied by nephrotic syndrome. We enrolled 125
      patients with MDS who were admitted between January 1979 and May 1996 in this
      study. The renal function was assessed based on the laboratory data and the
      findings at the physical examination. The diagnoses of nephrotic syndrome and
      glomerular disease were established when 24-hr urinary excretion was more than
      3.5 g and serum total protein was less than 6.0 g/dl, and when the 24-hr protein
      excretion was more than 1.5 g. Five patients (4%) had glomerular disease, and
      three (2.4%) had nephrotic syndrome. Of the five patients with glomerular
      disease, two had refractory anemia (RA), and three had chronic myelomonocytic
      leukemia (CMMOL). Three of the total 11 patients with CMMOL were diagnosed as
      having nephrotic syndrome. Among the CMMOL patients, those with nephrotic
      syndrome showed higher absolute monocyte numbers than did those without nephrotic
      syndrome (8830 +/- 4677/microl vs. 3061 +/- 2887/microl, P = 0.03). One CMMOL
      patient was treated with VP-16 and hydroxyurea. As the white blood cell count in
      this patient decreased, the 24-hr urine protein excretion and the serum tumor
      necrosis factor alpha level decreased. The relationship between nephrotic
      syndrome and CMMOL was not clear. High monocyte count and the serum cytokines in
      MDS patients may play a partial role in the evolution of glomerulonephritis, and
      CMMOL may be closely related to nephrotic syndrome.

PMID- 10072112
TI  - Detection of Epstein-Barr virus in Korean peripheral T-cell lymphoma.
AB  - One hundred thirty-seven patients with peripheral T-cell lymphomas (PTL) were
      examined for the presence of Epstein-Barr virus (EBV) using in situ hybridization
      for EBV-encoded RNA (EBER) and Bam H-fragment, lower strand frame (BHLF) and
      immunohistochemical stain for latent membrane protein (LMP). EBER was detected in
      tumor cells in 79 cases (58%); 26/66 PTL, unspecified (39%), 3/4 AILD (75%),
      47/51 angiocentric lymphomas (AL) (92%), and 3/13 anaplastic large cell lymphoma
      (ALCL) (23%) by Revised European-American Lymphoma (REAL) classification. EBER
      was detected in 17/36 nodal (47%) vs. 62/101 extranodal PTLs (61%); 21/24 nasal,
      12/32 Waldeyer's ring, 9/13 gastrointestinal, and 20/32 skin and soft tissue PTL.
      AL was consistently associated with the highest frequency of EBER among the
      extranodal PTL: nose (19/20), GI tracts (3/3), skin (14/15), and Waldeyer's ring
      (11/14). In extranodal lymphomas, coagulative-type zonal necrosis was seen almost
      exclusively in AL and showed correlation with EBER-positivity (P < 0.01). LMP was
      detected in 24 among 107 cases tested (22%). No signal for BHLF was detected in
      76 cases tested, implying absent or negligible incidence of lytic infection. In
      conclusion, high incidence of EBV was observed in PTL among Koreans, with
      predilection for angiocentric lymphomas and extranodal presentation, especially
      involving nose, skin, and gastrointestinal tract.

PMID- 10072113
TI  - Human herpesvirus-8 (HHV-8) associated with small non-cleaved cell lymphoma in a
      child with AIDS.
AB  - The association of human herpesvirus-8 (HHV-8) with a small non-cleaved cell
      lymphoma is described in a child with the acquired immunodeficiency syndrome
      (AIDS) who developed a malignant pleural effusion and radiologic evidence of
      multiple solid tumors. HHV-8 DNA and Epstein-Barr virus DNA were identified in
      pleural fluid cells by polymerase chain reaction (PCR) amplification. The serum
      antibody titer against lytic HHV-8 proteins was 1:640; antibodies to latent HHV-8
      proteins were not detected. Cytogenetic analysis of malignant cells revealed
      three abnormal karyotypes sharing the common finding of a t(8;14) translocation.
      Rearrangement of c-myc was demonstrated by PCR analysis. Oligoclonal JH
      immunoglobulin bands were found. Insufficient pleural fluid cells were available
      to permit localization of HHV-8 to malignant cells by in situ hybridization. This
      malignancy contrasts with HHV-8-associated lymphomas reported in adult patients
      with AIDS with respect to cell morphology, c-myc translocation, and oligoclonal
      immunoglobulin gene rearrangement. HHV-8 is associated with a wider spectrum of
      malignancies than recognized previously.

PMID- 10072114
TI  - Successful treatment of persistent erythroid aplasia caused by parvovirus B19
      infection in a patient with common variable immunodeficiency with low-dose
      immunoglobulin.
AB  - Parvovirus B19 causes persistent erythroid aplasia in immunocompromised hosts.
      From April through July 1996, we encountered five adult patients presenting with
      reticulocytopenia and fever caused by parvovirus B19 infection. The reticulocyte
      count of four patients with normal immunity recovered within two weeks after the
      onset of fever. However, in the one remaining patient with common variable
      immunodeficiency (CVI), reticulocytopenia, and other symptoms including fever and
      the elevation of lactate dehydrogenase (LDH) levels persisted beyond 16 days of
      onset. Although the DNA of parvovirus B19 was detected in the peripheral blood of
      the CVI patient, neither immunoglobulin Ig-G nor Ig-M antibodies specific to the
      virus were detectable. We administered 50 mg/kg of Ig to the CVI patient for six
      days. The reticulocyte count recovered promptly on the sixth day of the treatment
      and parvovirus B19 DNA was not detectable 30 days after therapy. This indicates
      that although patients with CVI may be susceptible to persistent erythroid
      aplasia during an endemic of parvovirus B19, the complication can be treated
      successfully with relatively low-dose Ig.

PMID- 10072115
TI  - Danazol therapy in cyclic acquired amegakaryocytic thrombocytopenic purpura: a
      case report.
AB  - Cyclic acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare
      disorder characterized by periodic fluctuations in the platelet counts due to a
      defect in the platelet production. We describe a 42-year-old female with cyclic
      AATP, in whom the cyclic fluctuations in the platelet counts ceased with danazol
      therapy. The pathogenesis of the disease and the possible mechanisms of danazol
      action have been reviewed.

PMID- 10072116
TI  - Waldenstrom's macroglobulinemia in young African-American adults.
AB  - We have identified five African-American patients with Waldenstrom's
      macroglobulinemia (WM) diagnosed at a young age (ages 35, 38, 38, 40, 51; 4
      males, 1 female). All had a history of intravenous heroin abuse and four also
      used cocaine. Their manner of presentation and clinical course were typical.
      Three of three patients tested for the hepatitis C virus (HCV) were positive and
      three of three patients tested were HIV negative. The potential relationship
      between intravenous drug abuse and/or HCV to development of WM in this group of
      young patients is provocative, especially since a polyclonal increase in serum
      IgM is commonly seen in chronic intravenous heroin addicts. More recently, the
      contribution of HCV is being evaluated in lymphoproliferative disorders. Although
      WM is typically a disease of older people, it should also be considered in the
      differential in a young patient with a suggestive clinical picture.

PMID- 10072117
TI  - Anticoagulant-induced skin necrosis in a patient with hereditary deficiency of
      protein S.
AB  - Skin necrosis is a rare but debilitating complication of treatment with vitamin K
      antagonist anticoagulants such as warfarin. A clinically similar syndrome has
      been reported less frequently with heparin therapy. We recently managed a thirty
      year-old female patient who developed skin necrosis on her left lower extremity
      while on warfarin for postpartum DVT. The lesions started to develop 48 hr after
      stopping heparin therapy. Discontinuation of warfarin and reinstitution of
      heparin was complicated by a rapid decrease in platelet count consistent with
      heparin-induced thrombocytopenia (HIT) and its associated risk of platelet
      activation and thrombosis. The diagnosis was supported by the identification of
      antibodies against heparin/platelet factor 4 complexes in the patient's serum.
      The platelet count recovered and the patient improved after switching to therapy
      with the heparinoid danaparoid. Evaluation for a hypercoagulable state revealed a
      partial deficiency of protein S, a condition that previously was identified in
      two of her family members. It is not clear if this patient suffered from warfarin
      induced skin necrosis, a manifestation of heparin-mediated platelet activation,
      or a complex condition in which both drugs contributed. HIT may affect 1-3% of
      patients who receive unfractionated heparin, and this case raises the possibility
      that heparin may contribute to, or cause, some episodes of skin necrosis
      attributed to warfarin. Because many patients who develop warfarin-induced skin
      necrosis have been treated initially with heparin, it would seem prudent to
      consider HIT in these situations.

PMID- 10072118
TI  - Takayasu's arteritis associated with factor V Leiden.
AB  - Takayasu's arteritis (TA) is a rare, chronic, and idiopathic vasculitis of the
      aorta and/or its main branches. There have been case reports of this disease
      associated with immune hypercoaguable states, namely raised antiphospholipid
      antibodies. Investigations of the thrombotic nature of Takayasu's arteritis have
      shown elevated levels of B-thromboglobulin, platelet factor 4, thrombin
      antithrombin III complex, and fibrinopeptide A. We report the first case of TA
      associated with the Factor V Leiden gene defect (Activated Protein C Resistance).
      The patient is a 30-year-old female who presented with six months of bilateral
      lower and upper extremity claudication, carotid artery tenderness, diminished
      brachial pulse and no measurable blood pressure in the left arm, an erythrocyte
      sedimentation rate (Westergren) of 62 mm/hr, and an angiogram meeting the
      clinical criteria for TA. Her symptoms showed a dramatic response to high-dose
      oral glucocorticosteroids and she was also maintained on long-term
      anticoagulation. This case illustrates that hereditary hypercoagulable states can
      coexist with acquired vasculitidies and that further investigation into these
      associations and their pathophysiologic interaction is warranted.

PMID- 10072119
TI  - Risk factors for thrombosis in nonembolic cerebrovascular disease.
AB  - Thirty-seven young patients (less than 42 years of age) presenting with sudden
      onset of idiopathic nonembolic cerebrovascular disease were evaluated for
      underlying prothrombotic factors. Activated protein C resistance (APC-R) was
      measured by Dahlback's method and the modified method using factor V-deficient
      plasma. Activities of antithrombin (AT) III, protein C and S were measured.
      Anticardiolipin antibody was estimated by ELISA and lupus anticoagulant by kaolin
      clotting tests. APC-R was the most common defect (21.62%) followed by AT III
      deficiency and presence of anticardiolipin antibodies (5.6% each). The latter two
      were present together in one case. It is thus concluded that APC-R is the most
      common defect underlying idiopathic nonembolic cerebrovascular infarction in
      young individuals.

PMID- 10072120
TI  - Vitamin E (alpha-tocopherol) does not inhibit platelet stimulation by oxidized
      low density lipoprotein in vitro.
AB  - Platelet-rich plasma were treated with increasing concentrations of vitamin E
      (alpha-tocopherol). Washed platelets were exposed to oxidized low density
      lipoprotein (LDL) and examined by aggregometry and electron microscopy. The
      treatment of washed platelets by oxidized LDL induced morphological signs of
      activation like pseudopodia formation and an increase in light transmission.
      Alpha-tocopherol in a range of 0.001-1.0 mmol had no inhibiting influences on
      platelet activation by oxidized LDL. These results indicate that the free radical
      scavenger vitamin E cannot directly inhibit platelet activation by oxidized LDL.
      It may be supposed that platelet activation by oxidized LDL does not occur in a
      radical-dependent mechanism.

PMID- 10072121
TI  - Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho
      (D) immune globulin (WinRho SD).
AB  - Alloimmunization to the D blood group antigen following the transfusion of D
      positive red blood cells to a D-negative recipient may be prevented in most
      persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until
      recently, the only RhIG approved by the US Food and Drug Administration (FDA) for
      this indication required intramuscular injection, an inconvenient and painful
      route for the relatively large volume that may be required. We describe the
      successful prevention of Rh alloimmunization following the unintentional
      transfusion of D-positive red blood cells to a D-negative infant by the
      intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention
      of post-transfusion Rh alloimmunization by intravenous administration. We believe
      that this more convenient and less painful approach should be the treatment of
      choice for preventing Rh alloimmunization following the transfusion of D-positive
      red cells to a D-negative recipient.

PMID- 10072122
TI  - A case of primary refractory Hodgkin's disease treated successfully with
      paclitaxel.

PMID- 10072123
TI  - Recurrent lymphocytic pleural effusion after intravenous immunoglobulin.

PMID- 10072124
TI  - Analysis of the Smad5 gene in hematological malignancies.

PMID- 10072125
TI  - Vancomycin-associated thrombocytopenia: case report and review of the literature.

PMID- 10072126
TI  - Hemoglobin SC and multiple myeloma.

PMID- 10072127
TI  - Desmoid tumors supervening in two patients with chronic lymphocytic leukemia.

PMID- 10072128
TI  - Severe life-threatening hyperphosphatemia associated with tumor lysis in a
      patient with acute lymphoblastic leukemia.

PMID- 10072129
TI  - Low seroprevalence of Helicobacter pylori in patients with leukemia.

PMID- 10072130
TI  - Uterine infiltration as first sign of acute myeloid leukemia.

PMID- 10072131
TI  - Comparison of a parasite lactate dehydrogenase-based immunochromatographic
      antigen detection assay (OptiMAL) with microscopy for the detection of malaria
      parasites in human blood samples.
AB  - Microscopic examination of blood smears remains the gold standard for malaria
      diagnosis, but is labor-intensive and requires skilled operators. Rapid dipstick
      technology provides a potential alternative. A study was conducted in The Gambia
      to compare the performance of OptiMAL, an immunochromatographic antigen detection
      assay for the diagnosis of malaria using parasite lactate dehydrogenase, against
      standard microscopy in patients with suspected malaria. For initial diagnosis of
      Plasmodium falciparum, irrespective of stage, this assay had a sensitivity of
      91.3%, a specificity of 92%, a positive predictive value of 87.2%, and a negative
      predictive value of 94.7%. The sensitivity of the test decreased markedly at
      parasitemias < 0.01%. This assay can be used for the diagnosis of malaria in
      areas where microscopy is not available and for urgent malaria diagnosis at night
      and at weekends, when routine laboratories are closed and when relatively
      inexperienced microscopists may be on duty.

PMID- 10072132
TI  - Comparison of five methods of malaria detection in the outpatient setting.
AB  - In eastern Africa where 90% of the malaria is due to Plasmodium falciparum, the
      accuracy of malaria diagnosis at the outpatient level is becoming increasingly
      important due to problems of drug resistance and use of alternative, costly
      antimalarial drugs. The quantitative buffy coat (QBC) technique, acridine orange
      staining with an interference filter system, and the ParaSight-F test have been
      introduced as alternative methods to conventional microscopy for the diagnosis of
      malaria. Two hundred thirteen outpatients were tested using these alternative
      methods and conventional microscopy by five experienced technologists; two were
      randomly allocated to read the results of each test. Paired results showed the
      highest level of agreement with the ParaSight-F test (99%), followed by Field
      stain (92%). The results of the QBC technique showed the least agreement (73%).
      Using conventional microscopy as the reference standard, the ParaSight-F test had
      a sensitivity range of 90-92% and a specificity of 99%, staining with acridine
      orange had a sensitivity range of 77-96% and a specificity range of 81-98% and
      the QBC technique had a sensitivity range of 88-98% and a specificity range of 58
      90%. All microscopic tests showed lower sensitivities (as low as 20% using
      staining with acridine orange) in detecting low parasitemias (< or = 320/microl)
      than the ParaSight-F test (70%). Due to the high cost of the ParaSight-F test,
      Field-stained blood films remain the most appropriate method for diagnosis of P.
      falciparum in eastern Africa. The ParaSight-F test may be used in situations
      where no trained microscopists are available, or where malaria is strongly
      suspected and the results of microscopy are negative.

PMID- 10072133
TI  - Semi-nested, multiplex polymerase chain reaction for detection of human malaria
      parasites and evidence of Plasmodium vivax infection in Equatorial Guinea.
AB  - A semi-nested, multiplex polymerase chain reaction (PCR) based on the
      amplification of the sequences of the 18S small subunit ribosomal RNA (ssrRNA)
      gene was tested in a field trial in Equatorial Guinea (a hyperendemic focus of
      malaria in west central Africa). The method uses a primary PCR amplification
      reaction with a universal reverse primer and two forward primers specific for the
      genus Plasmodium and to mammals (the mammalian-specific primer was included as a
      positive control to distinguish uninfected cases from inhibition of the PCR). The
      second amplification is carried out with the same Plasmodium genus-specific
      forward primer and four specific reverse primers for each human Plasmodium
      species. The PCR amplified products are differentiated by fragment size after
      electrophoresis on a 2% agarose gel. Four villages from three regions of the
      island of Bioko (Equatorial Guinea) and two suspected Plasmodium vivax-P. ovale
      infections from the hospital of Malabo were tested by microscopy and PCR. The PCR
      method showed greater sensitivity and specificity than microscopic examination
      and confirmed the existence of a focus of P. vivax infections in Equatorial
      Guinea suspected by microscopic examination. It also provided evidence of several
      mixed infections, mainly P. falciparum and P. malariae, the two predominant
      species causing malaria in Equatorial Guinea.

PMID- 10072134
TI  - Differential serodiagnosis for cystic and alveolar echinococcosis using fractions
      of Echinococcus granulosus cyst fluid (antigen B) and E. multilocularis
      protoscolex (EM18).
AB  - Echinococcus granulosus cyst fluid and E. multilocularis protoscolex extract were
      fractionated by a single step of preparative isoelectric focusing, resulting in
      an antigen B-rich fraction (8-kD) and an Em18-rich fraction, respectively. The
      usefulness of both fractions for differential serodiagnosis of cystic (CE) and
      alveolar (AE) echinococcosis was evaluated by a large-scale immunoblot analysis
      on a battery of 354 serum samples. These included 66 from AE patients originating
      from four different endemic areas, 173 from CE patients originating from seven
      different endemic areas, 71 from patients with other parasitic diseases, 15 from
      patients with hepatomas, and 29 from healthy individuals. In an immunoblot with
      the antigen B-rich fraction, 92% (158 of 173) of the CE sera as well as 79% (52
      of 66) of the AE sera reacted with the 8-kD subunit. No cross-reactivity occurred
      with any sera from patients with cysticercosis, other parasitic diseases, or with
      hepatomas, or from healthy controls. In an immunoblot with the Em18-rich
      fraction, all but two sera from AE patients (64 of 66, 97%) recognized Em18, and
      only nine of 34 CE sera from China reacted with it. All other (139) CE sera from
      six other countries were negative as were all (115) other non-echinococcosis
      sera. These findings indicate that antigen B (8-kD) is not species-specific for
      E. granulosus but is genus-specific for Echinococcus, and that the Em18 antigen
      is a reliable serologic marker for species-specific differentiation of AE from
      CE.

PMID- 10072135
TI  - Differential immunodiagnosis between cystic hydatid disease and other cross
      reactive pathologies.
AB  - We assessed an Echinococcus granulosus hydatid fluid antigen-ELISA (EgHF-ELISA)
      as a serologic prescreening test for E. granulosus infections, supplemented by
      more specific confirmatory tests, including arc-5 immunoprecipitation and antigen
      B subunit 8-kD immunoblotting. The diagnostic sensitivity of the EgHF-ELISA was
      91%. With regard to the test specificity of the EgHF-ELISA (overall = 82%), we
      observed relatively frequent cross-reactions in tumor patients (6%) and in
      patients with other parasitic diseases. Cestode-related cross-reactivity can be
      resolved by the complementary use of E. multilocularis-specific antigens or
      Taenia solium cysticercosis-specific immunoblotting. Immunoblotting based upon
      the detection of antibody reactivity to the 8-kD antigen of EgHF, or if
      appropriately detectable, to the 29-kD and 34-kD bands exhibited a 91% diagnostic
      sensitivity and an overall specificity of 97% or 94%, respectively. Thus,
      immunoblotting provided a 99% discrimination between seropositive pre-operative
      cystic hydatid disease cases and cross-reactive non-cestode parasitic infections
      or malignancies.

PMID- 10072136
TI  - Development of a serologic assay to detect Taenia solium taeniasis.
AB  - We developed a serologic assay to identify adult Taenia solium tapeworm carriers
      using excretory/secretory (TSES) antigens collected from in vitro cultured T.
      solium tapeworms. To identify taeniasis-specific antigens we used an immunoblot
      assay with serum samples from T. solium tapeworm carriers and cysticercosis
      patients. Antigens were identified that reacted with antibodies present in serum
      samples from taeniasis cases and not with those from cysticercosis patients.
      Using serum samples collected from persons with confirmed T. solium tapeworm
      infections, the test was determined to be 95% (69 of 73) sensitive. Serum samples
      (n = 193) from persons with other parasitic infections, including T. saginata
      tapeworm infections, do not contain cross-reacting antibodies to TSES, indicating
      that the assay is 100% specific. These data suggest that the immunoblot assay
      using TSES antigens can be used to identify persons with current or recent T.
      solium tapeworm infections and provides a new, important tool for epidemiologic
      purposes, including control and prevention strategies.

PMID- 10072137
TI  - Chagas' disease diagnosis: comparative analysis of parasitologic, molecular, and
      serologic methods.
AB  - During the course of chronic chagasic infection, low parasitemia levels prevent
      parasite detection by current techniques such as hemoculture and xenodiagnosis.
      Since serologic tests have sensitivity but lack specificity, molecular assays
      based on the polymerase chain reaction (PCR) have been proposed as alternative
      tools for parasite detection in individuals with chronic Chagas' disease. A
      variable degree of PCR efficiency has been reported in the literature and
      illustrates the need for further evaluation of large numbers of chagasic
      patients. In this study, we compared an optimized PCR technique with hemoculture
      and complement-mediated lysis (CoML) in 113 individuals from or living in endemic
      areas of Brazil who had conventional serologic results that were either positive,
      negative, or inconclusive. The PCR amplification yielded positive results in
      83.5% (66 of 79) of individuals with positive serology, 47.6% (10 of 21) with
      negative serology, and 46.2% (6 of 13) with inconclusive serology. Of 10 patients
      with negative serology and positive PCR result, eight (80%) had positive CoML,
      indicating that they could have been chagasic but were not mounting immune
      responses. The PCR results were also positive for all individuals who had
      positive hemoculture, for 37 individuals with negative hemoculture and positive
      serology, and for two of six individuals with inconclusive serology and negative
      hemoculture. Thirteen individuals living in nonendemic areas who had negative
      serology were used as a negative control group: 100% had negative PCR results.
      Our results show that the optimized PCR protocol used here was very sensitive in
      detecting the presence of Trypanosoma cruzi in chronic chagasic patients. The PCR
      and CoML results were well correlated in all of the groups studied, which
      suggests that our PCR protocol may be effective in the evaluation of cure in
      patients who receive anti-parasite treatment.

PMID- 10072138
TI  - Enzyme-linked immunosorbent assay for IgA antibodies to Trypanosoma cruzi in
      congenital infection.
AB  - With the aim of achieving earlier diagnosis of congenital Trypanosoma cruzi
      infection, we assessed the usefulness of detecting specific IgA antibody by an
      ELISA. We evaluated 12 pregnant women chronically infected with T. cruzi, their
      newborn infants, and three additional neonates with parasitemia at birth. The IgA
      specific antibody was detected by adapting the procedure for use of a commercial
      IgG ELISA, the Hemagen Chagas' Kit (Hemagen Diagnostics, Inc., Waltham, MA).
      Trypanosoma cruzi-specific IgA was detected in 10 (83%) of 12 mothers at
      delivery, in one of three parasitemic infants, and one of 12 newborns of the
      chronically infected women. Testing of 13 infants at six months of age revealed
      IgA in seven infants (54%), of whom four also had persistent T. cruzi-specific
      IgG. Detection of T. cruzi-specific IgA could provide a criterion for diagnosis
      of congenital infection in the absence of detectable parasitemia.

PMID- 10072139
TI  - Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and
      epidemiologic study.
AB  - A clinical, parasitologic, and serologic study carried out between 1988 and 1996
      on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is
      endemic showed 19 symptomatic patterns or groups of symptoms appearing in
      combination with different frequencies. The symptomatic pattern with the highest
      frequency was that showing simultaneously fever, myalgia, headache, and Romana's
      sign, which was detected in 20% of the acute-phase patients. Asymptomatic
      individuals and patients with fever as the only sign of the disease made up 15%
      and 11.9% of the total acute cases, respectively. Statistical correlation
      analysis revealed that xenodiagnosis and hemoculture were the most reliable and
      concordant of the five parasitologic methods used; these two methods also showed
      the highest proportions in detecting any clinical symptomatic pattern in acute
      phase patients. A similar high reliability and concordance was obtained with a
      direct agglutination test, an indirect immunofluorescent antibody test, and an
      ELISA as serologic tests, which also showed a higher proportion of positive
      detection of clinical patterns than parasitologic methods (P < 0.001). It is
      recommended that individuals coming from endemic areas showing mild and/or severe
      clinical manifestations should be suspected of being in contact or having been in
      contact with Trypanosoma cruzi, be referred for parasitologic and serologic
      evaluations to confirm the presumptive clinical diagnosis of acute Chagas'
      disease, and start specific treatment. The epidemiologic implications of the
      present findings are discussed and the use of similar methodology to evaluate
      other areas where Chagas' disease is endemic is suggested.

PMID- 10072140
TI  - Pathogenesis of cancrum oris (noma): confounding interactions of malnutrition
      with infection.
AB  - This study showed that impoverished Nigerian children at risk for cancrum oris
      (noma) had significantly reduced plasma concentrations of zinc (< 10.8
      micromol/L), retinol (< 1.05 micromol/L), ascorbate (< 11 micromol/L), and the
      essential amino acids, with prominently increased plasma and saliva levels of
      free cortisol, compared with their healthy counterparts. The nutrient
      deficiencies, in concert with previously reported widespread viral infections
      (measles, herpesviruses) in the children, would impair oral mucosal immunity. We
      postulate, subject to additional studies, that evolution of the oral mucosal
      ulcers including acute necrotizing gingivitis to noma is triggered by a
      consortium of microorganisms of which Fusobacterium necrophorum is a key
      component. Fusobacterium necrophorum elaborates several dermonecrotic toxic
      metabolites and is acquired by the impoverished children via fecal contamination
      resulting from shared residential facilities with animals and very poor
      environmental sanitation.

PMID- 10072141
TI  - Treatment of malarial acute renal failure by hemodialysis.
AB  - We studied 112 patients with malarial acute renal failure (ARF) during the period
      1991-1997 at Bangkok Hospital for Tropical Diseases (Mahidol University, Bangkok,
      Thailand). Hemodialysis was performed in 101 (90.2%) of these patients. The mean
      number of times the patients were hemodialyzed was 6.5 (range = 1-27). Ninety
      three (83.0%) patients were oliguric and the remainder were nonoliguric. Patients
      who had oliguric renal failure required more hemodialyses and had more
      complications than the nonoliguric patients. The oliguric patients had an eight
      fold higher risk of requiring six or more hemodialyses (95% confidence interval =
      1.2-53.9, P = 0.0008). The overall mortality rate was 10.7% (12 of 112). Eleven
      of the patients who died were jaundiced and eight of them had cerebral malaria
      with a Glasgow Coma Score < or = 8. We conclude that hemodialysis is a useful
      treatment for oliguric and nonoliguric ARF from severe malaria, particularly when
      initiated early in the course of the illness.

PMID- 10072142
TI  - A randomized, double-blind, comparative trial of a new oral combination of
      artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute
      Plasmodium falciparum malaria in Thailand.
AB  - CGP 56697, a new oral fixed combination of artemether and benflumetol, was tested
      in a double-blinded, randomized trial in 252 adult patients treated either with
      CGP 56697 (4 x 4 tablets each containing 20 mg of artemether and 120 mg of
      benflumetol, given at 0, 8, 24, and 48 hr), or with mefloquine (three tablets of
      250 mg at initial diagnosis, followed by two tablets of 250 mg at 8 hr). Baseline
      data of the two groups were comparable. The 28-day cure rate with CGP 56697 was
      lower than with mefloquine (69.3% versus 82.4%; P = 0.002). However, CGP 56697
      was more effective than mefloquine in parasite clearance time (43 hr versus 66
      hr; P < 0.001) fever clearance time (32 hr versus 54 hr; P < 0.005), and
      gametocyte clearance time (152 hr versus 331 hr; P < 0.001). This study revealed
      that CGP 56697 is effective against multidrug-resistant Plasmodium falciparum
      malaria in Thailand, but higher doses will probably be needed to improve the cure
      rate.

PMID- 10072143
TI  - The pharmacokinetics of artemisinin after administration of two different
      suppositories to healthy Vietnamese subjects.
AB  - Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated
      into fatty suppositories (FS), and six different subjects received 500 mg of
      artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma
      concentrations were measured by high-performance liquid chromatography with
      electrochemical detection; concentration versus time curves were analyzed with
      nonparametric methods. No statistically significant differences were found
      between the two formulations. The maximum concentration (Cmax) was 100 +/- 102
      microg/L (mean +/- SD, range = 24-330) microg/L (FS), the pharmacokinetic lag
      time (Tlag) was 1.3 +/- 1.0 hr (range = 0-3) (FS), and the time of the maximum
      concentration (Tmax) was 7.1 +/- 2.1 hr (range = 3-10) hr (FS). Because
      artemisinin is not available for intravenous dosage, absolute bioavailability
      cannot be assessed. However, compared with a previous study on oral artemisinin
      in healthy Vietnamese subjects, bioavailability relative to oral administration
      was estimated to be approximately 30%. We conclude that therapeutic blood
      concentrations of artemisinin can be reached after rectal dosage. The dose after
      rectal administration should probably be higher than after oral administration;
      doubling or tripling the oral dose might be necessary, which would imply a rectal
      dose of at least 20 mg/kg of body weight given twice a day.

PMID- 10072144
TI  - Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax
      malaria.
AB  - Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion
      molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin
      have been reported in several diseases. However, plasma or serum levels of TM,
      ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of
      Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine
      levels were determined in six Japanese patients in the acute phase of vivax
      malaria and in seven healthy Japanese controls. Parasitemias of the peripheral
      blood were < 0.1% in five patients and 0.8% in one patient. The patients' mean +/
      SD serum levels of TM, ICAM-1, VCAM-1, and E-selectin were 5.7 +/- 1.3 Fujirebio
      units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml,
      respectively, and all were significantly greater than those in the controls (TM;
      P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However,
      no significant difference was identified between patients and controls for serum
      creatinine values. The serum levels of TM and VCAM-1 were not related to
      parasitemia. The elevation of serum TM levels suggests that endothelial cell
      damage occurs in the acute phase of vivax malaria.

PMID- 10072145
TI  - Granulomatous inflammatory response to recombinant filarial proteins of Brugia
      species.
AB  - The lymphatic inflammatory response in Brugia-infected jirds peaks early during
      primary infections and then decreases in severity as judged by the numbers of
      lymph thrombi present within these vessels. Antigen-specific hypersensitivity
      reactions in these animals was measured by a pulmonary granulomatous inflammatory
      response (PGRN) induced by somatic adult worm antigen (SAWA)-coated beads, and by
      cellular proliferative responses of renal lymph node cells. The kinetics of these
      responses temporally correspond to lymphatic lesion formation. The importance of
      any single antigen to the induction of this inflammatory response has not been
      elucidated. In this study, the PGRN was used to measure the cellular immune
      response to four recombinant filarial proteins during the course of a primary B.
      pahangi infection. These proteins were BpL4, glycoprotein (glutathione
      peroxidase) gp29, heat shock protein (hsp) 70, and filarial chitinase. All were
      fusion proteins of maltose-binding protein (MBP). Control beads included those
      coated with diethanolamine (DEA), SAWA, or MBP. The measurements of PRGN were
      made at 14, 28, 56, and > 150 days postinfection (PI) in infected jirds, in jirds
      sensitized with SAWA, and in uninfected jirds. The secretory homolog of
      glutathione peroxidase gp29 was the only recombinant protein tested that induced
      a significantly greater PGRN (P < 0.05) than controls. This was seen at 28 days
      PI. These observations indicate that gp29 may be part of the worm antigen complex
      that induces an early inflammatory response, a response similar to that observed
      with SAWA. These studies indicate that this approach is useful in investigating
      the functional ability of specific proteins in the induction and down-regulation
      of immune-mediated inflammatory responses elicited by filarial parasites. Absence
      of a granulomatous response to the other recombinant proteins used may be related
      to the nature and sensitivity of the assay used or the character of recombinant
      proteins tested.

PMID- 10072146
TI  - Neurocysticercosis in an Italian traveler to Latin America.
AB  - Neurocysticercosis is rarely reported in short-term travelers, although the
      disease remains a major public health problem in tropical regions. We present a
      case of neurocysticercosis that was probably acquired by ingestion of Taenia
      solium eggs contained in the stomach of a pig butchered by the traveler. Complete
      clinical resolution was obtained by medical treatment, underlying the importance
      of early suspicion and diagnosis of the disease.

PMID- 10072147
TI  - Prevalence of intestinal parasite infections with special reference to Entamoeba
      histolytica on the island of Bioko (Equatorial Guinea).
AB  - The prevalence of intestinal parasitic infections was assessed (1993 through
      1995) among two different groups of persons on the island of Bioko, Equatorial
      Guinea. In the first group, parasitologic examinations were performed on stool
      specimens from a household-based sample of 557 dwellers from the rural area of
      the island. In the second group, 1,633 inpatients and outpatients at the General
      Hospital of Malabo (the capital of the country) were studied. All age groups were
      represented in both groups. The average prevalence of the most common protozoan
      and helminthic intestinal infections in rural and urban areas, respectively, was
      as follows: Entamoeba histolytica/E. dispar (14.9% and 32.7%, respectively),
      Giardia lamblia (7.2% and 8.6%), Ascaris lumbricoides (45.8% and 31.4%), and
      Trichuris trichiura (25.7% and 36.4%). Seventy-nine sera from patients with
      amebic liver abscess (suspected by ultrasonography) were studied by an
      immunohemagglutination assay, with 44 (56%) showing anti-E. histolytica titers >
      or = 1:32. Of these 79 sera, 71 were studied by an enzyme immunoassay, 86% of
      which were positive with titers > or = 1:64. This study showed that parasitic
      infections in Equatorial Guinea represent a major health problem.

PMID- 10072148
TI  - A case-control study of risk factors for Haemophilus influenzae type B disease in
      Navajo children.
AB  - To understand the potential risk factors and protective factors for invasive
      Haemophilus influenzae type b (Hib) disease, we conducted a case-control study
      among Navajo children less than two years of age resident on the Navajo Nation.
      We analyzed household interview data for 60 cases that occurred between August
      1988 and February 1991, and for 116 controls matched by age, gender, and
      geographic location. The Hib vaccine recipients were excluded from the analyses.
      Conditional logistic regression models were fit to examine many variables
      relating to social and environmental conditions. Risk factors determined to be
      important were never breast fed (odds ratio [OR] = 3.55, 95% confidence interval
      [CI] = 1.52, 8.26), shared care with more than one child less than two years of
      age (OR = 2.32, 95% CI = 0.91, 5.96); wood heating (OR = 2.14, 95% CI = 0.91,
      5.05); rodents in the home (OR = 8.18, 95% CI = 0.83, 80.7); and any livestock
      near the home (OR = 2.18, 95% CI = 0.94, 5.04).

PMID- 10072149
TI  - Risk of Helicobacter pylori infection among long-term residents in developing
      countries.
AB  - The seroprevalence and incidence of Helicobacter pylori infection were determined
      among 312 North American missionaries who were serving in developing countries
      between 1967 and 1984. The majority (81%) resided in sub-Saharan Africa. When
      initially evaluated, the missionaries had a mean age of 40 years, 65% were
      female, and all were of white race/ethnicity. An ELISA showed that the initial
      prevalence of IgG antibody to H. pylori was 17%. After a mean of 7.4 years of
      service (1917 person-years of exposure), 37 (14%) of 259 initially seronegative
      subjects seroconverted to anti-H. pylori, giving an annual incidence of 1.9%.
      These data indicate a relatively higher risk of H. pylori infection among
      missionaries compared with an annual incidence of seroconversion of 0.3-1.0% in
      industrialized nations. Long-term residents in developing countries should be
      evaluated for H. pylori infection when gastrointestinal symptoms develop.

PMID- 10072150
TI  - Transmission of epidemic Vibrio cholerae O1 in rural western Kenya associated
      with drinking water from Lake Victoria: an environmental reservoir for cholera?
AB  - Sub-Saharan Africa has the highest reported cholera incidence and mortality rates
      in the world. In 1997, a cholera epidemic occurred in western Kenya. Between June
      1997 and March 1998, 14,275 cholera admissions to hospitals in Nyanza Province in
      western Kenya were reported. There were 547 deaths (case fatality rate = 4%). Of
      31 Vibrio cholerae O1 isolates tested, all but one were sensitive to
      tetracycline. We performed a case-control study among 61 cholera patients and age
      , sex-, and clinic-matched controls. Multivariate analysis showed that risk
      factors for cholera were drinking water from Lake Victoria or from a stream,
      sharing food with a person with watery diarrhea, and attending funeral feasts.
      Compared with other diarrheal pathogens, cholera was more common among persons
      living in a village bordering Lake Victoria. Cholera has become an important
      public health concern in western Kenya, and may become an endemic pathogen in the
      region.

PMID- 10072151
TI  - Prevalence of enteric hepatitis A and E viruses in the Mekong River delta region
      of Vietnam.
AB  - A study of antibody prevalence for hepatitis A virus (HAV) and hepatitis E virus
      (HEV) was carried out in southwestern Vietnam in an area adjacent to a known
      focus of epidemic HEV transmission. The purpose of this investigation was first
      to provide a prevalence measure of hepatitis infections, and second to determine
      the outbreak potential of HEV as a function of the susceptible population. Blood
      specimens collected from 646 persons in randomly selected village hamlets were
      examined by an ELISA for anti-HEV IgG and anti-HAV IgG. The prevalences of anti
      HEV IgG and anti-HAV IgG were 9% and 97%, respectively. There was a significant
      increase (P < 0.01) in age-specific anti-HEV IgG. A notable increase in anti-HAV
      IgG prevalence (P < 0.0001) occurred between child populations 0-4 (64%) and 5-9
      (95%) years of age. No evidence of familial clustering of anti-HEV IgG-positive
      individuals was detected, and household crowding was not associated with the
      spread of HEV. Boiling of water was found to be of protective value against HEV
      transmission. A relatively low prevalence of anti-HEV indicates considerable HEV
      outbreak potential, against a background of 1) poor, water-related
      hygiene/sanitation, 2) dependence on a (likely human/animal waste)-contaminated
      Mekong riverine system, and 3) periodic river flooding.

PMID- 10072152
TI  - Vectors of Chikungunya virus in Senegal: current data and transmission cycles.
AB  - Chikungunya fever is a viral disease transmitted to human beings by Aedes genus
      mosquitoes. From 1972 to 1986 in Kedougou, Senegal, 178 Chikungunya virus strains
      were isolated from gallery forest mosquitoes, with most of them isolated from Ae.
      furcifer-taylori (129 strains), Ae. luteocephalus (27 strains), and Ae. dalzieli
      (12 strains). The characteristics of the sylvatic transmission cycle are a
      circulation periodicity with silent intervals that last approximately three
      years. Few epidemics of this disease have been reported in Senegal. The most
      recent one occurred in 1996 in Kaffrine where two Chikungunya virus strains were
      isolated from Ae. aegypti. The retrospective analysis of viral isolates from
      mosquitoes, wild vertebrates, and humans allowed to us to characterize
      Chikungunya virus transmission cycles in Senegal and to compare them with those
      of yellow fever virus.

PMID- 10072153
TI  - Isolation of tick-borne encephalitis virus from wild rodents and a
      seroepizootiologic survey in Hokkaido, Japan.
AB  - To determine the vertebrate host of tick-borne encephalitis (TBE) virus in the
      southern part of Hokkaido, Japan, virus isolation was performed using spleens
      from small mammals captured in the area. Two virus strains were isolated, one
      strain from Apodemus speciosus and another from Clethrionomys rufocanus. Virus
      isolates were inoculated onto baby hamster kidney cell monolayers and antigen
      slides were prepared for an indirect immunofluorescent antibody assay. Two
      isolates were identified as TBE viruses by monoclonal antibody reactions. To
      specify the TBE-endemic area in Hokkaido, rodent, horse, and dog sera collected
      from 1992 to 1997 were tested for neutralization antibody against TBE virus
      previously isolated from a dog. The positive cases were distributed in four
      districts in the southern part of Hokkaido.

PMID- 10072154
TI  - Variation in oral susceptibility to dengue type 2 virus of populations of Aedes
      aegypti from the islands of Tahiti and Moorea, French Polynesia.
AB  - Twenty three samples of Aedes aegypti populations from the islands of Tahiti and
      Moorea (French Polynesia) were tested for their oral susceptibility to dengue
      type 2 virus. The high infection rates obtained suggest that the artificial
      feeding protocol used was more efficient than those previously described.
      Statistical analysis of the results allowed us to define two distinct geographic
      areas on Tahiti with respect to the susceptibility of Ae. aegypti: the east
      coast, with homogeneous infection rates, and the west coast, with heterogeneous
      infection rates. No geographic differences could be demonstrated on Moorea. The
      possible mechanisms of this phenomenon are discussed in connection with recent
      findings on the variability of susceptibility of Ae. aegypti to insecticides.

PMID- 10072155
TI  - Serologic evidence for an epizootic dengue virus infecting toque macaques (Macaca
      sinica) at Polonnaruwa, Sri Lanka.
AB  - Dengue is one of the most rapidly emerging diseases in the tropics. Humans are
      the principal reservoir of dengue viruses. It is unclear if nonhuman primates
      also serve as a reservoir of human dengue viruses under certain conditions. In
      this study, a cross-sectional serologic survey was carried out to characterize
      the pattern of transmission of a recently identified dengue virus among toque
      macaques in Sri Lanka. The results indicated that an epizootic dengue virus was
      active among the macaques. A single epizootic had taken place between October
      1986 and February 1987 during which 94% of the macaques within the 3 km2 study
      site were exposed to the virus. The epizootic was highly focal in nature because
      macaques living 5 km from the study population were not exposed to the virus. The
      transmission of dengue viruses among macaques in the wild may have important
      public health implications.

PMID- 10072156
TI  - Mortality due to schistosomiasis mansoni: a field study in Sudan.
AB  - Although schistosomiasis affects 200 million persons, 20 million of whom have
      advanced disease, little is known about the mortality pattern in areas of endemic
      schistosomiasis mansoni. In an attempt to assess the mortality rates in an
      endemic area in Sudan, we conducted two demographic surveys in a village in the
      Gezira area. Clinical, sonographic, and parasitologic examinations were performed
      in a randomly selected sample of 25% of the population in 1987 and 1994. One of
      us asked each head of household about the names, sex, and age of family members.
      Particularly, we asked about death in the family if any, history of
      schistosomiasis, abdominal swelling, and hematemesis. Possible causes of death
      were ascertained by reviewing medical records in the village dispensary and the
      district hospital. There were 42 deaths in the village. Four males died of
      hematemesis secondary to portal fibrosis. The crude mortality rate of
      schistosomiasis was is 51/100,000/year. The overall schistosomiasis fatality rate
      per year was 1/1,000 infected persons, but was as high as 11/100/infected
      patients with bleeding varices. These findings showed the impact of
      schistosomiasis on public health in this economically important region of Sudan.

PMID- 10072157
TI  - Congenital transmission of Schistosoma japonicum in pigs.
AB  - Congenital transmission of Schistosoma japonicum in pigs was investigated by
      experimentally infecting sows at four weeks gestation (n = 3), 10 weeks gestation
      (n = 3), or a few weeks prior to insemination (n = 2). None of the piglets born
      to sows infected prior to insemination or in early pregnancy were found to be
      infected. However, all of the piglets (n = 26) born to sows infected at 10 weeks
      gestation were found to harbor schistosomes with S. japonicum eggs recovered from
      both their feces and livers. The findings show that congenital S. japonicum
      infection of pigs can occur if sows are infected during mid-to-late pregnancy and
      may have important implications not only for pigs but also for other mammalian
      hosts of schistosomes, including humans.

PMID- 10072159
TI  - Replication of dengue type 2 virus in Culex quinquefasciatus (Diptera:
      Culicidae).
AB  - We were able to infect Culex quinquefasciatus by the parenteral route with dengue
      virus type 2. The percentage of mosquitoes infected was dose dependent and we
      obtained a rate of 45.6% infected Cx. quinquefasciatus when a 10(5.9) MID50
      (mosquito infectious dose for 50% of the individuals as measured in Aedes
      aegypti) of dengue virus type 2 per mosquito was used. Infection was detected by
      an immunofluorescent assay performed on mosquito head squashes 14 days after
      infection. The replication of dengue virus in Cx. quinquefasciatus was either at
      a very low level of magnitude or generated a large number of noninfectious
      particles since the triturated bodies of infected Cx. quinquefasciatus did not
      infect Ae. aegypti mosquitoes when inoculated parenterally. We were unable to
      infect Cx. quinquefasciatus females orally with an artificial meal that infected
      100% of Ae. aegypti females. These findings lead us to agree with the consensus
      that Cx. quinquefasciatus should not be considered a biological vector of dengue
      viruses.

PMID- 10072158
TI  - Age-specific decrease in seroprevalence of schistosomiasis in Puerto Rico.
AB  - In our previous work, we reported the first systematic, island-wide, serologic
      survey for schistosomiasis in Puerto Rico in 40 years. In that study,
      approximately 3,000 serum samples from the 76 municipalities comprising the
      island of Puerto Rico were tested for the detection of antibodies to S. mansoni
      microsomal antigens by the Falcon assay screening test-enzyme-linked
      immunosorbent assay (FAST-ELISA) and those positive were confirmed by an enzyme
      linked immunoelectrotransfer blot (EITB). The highest EITB positivity was found
      in 17 municipalities, which comprised 48% of all seropositive samples. An
      additional finding was that 10% of the 215 EITB-positive samples were from
      individuals 25 years or younger and were for the most part of residents from the
      high seroprevalence areas. Thus, for this study we focused on 766 individuals 25
      years of age or younger (45.5% males and 54.4% females), two-thirds of which were
      from 10 municipalities with the highest EITB seropositivity, and one-third from
      the 10 municipalities with the lowest EITB seropositivity found in our previous
      study. Of all samples, the results showed an overall FAST-ELISA positivity of
      11.6%, with males similar to females (12.6 versus 10.7%, respectively).
      Confirmation by EITB was only 1.8%, with a males three-fold higher than females
      (3% versus 0.7%). When seropositivity was measured by age in five-year
      increments, a clear age-specific decrease in seropositivity was observed. Thus,
      by FAST-ELISA, 16.7% of the 21-25-year-old age group was positive, decreasing to
      14.6%, 9.9%, 7.9%, and 9.3% in the 16-20-, 11-15-, 6-10-, and 1-5-year-old age
      groups, respectively. Confirmatory EITB showed even more impressive results:
      4.7%, 2.6%, 1.2%, 0.7%, and 0% in the same age brackets. With regard to the high
      prevalence municipalities, only four of 10 (11 of 228 = 4.8%) had confirmatory
      EITB-positive samples and most were from municipalities of the Rio Grande de
      Loiza River basin and tributaries. The male to female positivity ratio was 4:1.
      Of the low prevalence municipalities, only single positive cases (by EITB) were
      found in three disperse municipalities. These results support the concept that
      there has been little transmission of S. mansoni in Puerto Rico during the first
      half of the 1990s and confirms anecdotal comments of local physicians who have
      seen virtually no new infections during the past three years. This makes the
      documentation of eradication of schistosomiasis from Puerto Rico feasible, a goal
      that should be set as being before the 100th anniversary of its discovery on the
      island by Isaac Gonzalez-Martinez in 1904.

PMID- 10072160
TI  - Decreased lactic acidosis and anemia after transfusion of o-raffinose cross
      linked and polymerized hemoglobin in severe murine malaria.
AB  - Severe anemia is a major cause of death in falciparum malaria. Blood transfusion
      increases survival in humans and in animal models of this disease. Because of
      logistic constraints and viral contamination of the blood supply, transfusions
      are frequently not practical in endemic regions. Modified hemoglobin is an
      effective O2 carrier in hemorrhagic shock. It is free of infectious
      contamination, may not require refrigeration, and because of its nitric oxide
      scavenging and small size, may have pharmacologic benefits in malaria. The
      effects of transfusions of modified hemoglobin in rats with high-grade
      parasitemia were evaluated. Modified hemoglobin decreased lactic acidosis and
      corrected anemia as well as transfusions with red blood cells; these findings may
      correlate with improved survival and suggest a possible proerythropoietic effect.
      Further study of this novel therapy is warranted.

PMID- 10072161
TI  - A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a
      rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a cutaneous tumour of borderline
      malignancy, the cytogenetic features of which include the translocation
      t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing
      material from 17q22 and 22q13. These rearrangements result in the COL1A1/PDGFB
      fusion gene. Here, we describe a case of DFSP displaying a ring chromosome 5
      together with a large marker chromosome composed of chromosome 22 alphoid DNA,
      material from distal 12q and amplified COL1A1 and PDGFB sequences. This is the
      first case of DFSP with multiple copies of COL1A1 and PDGFB not confined to ring
      chromosomes, showing that DFSP is similar to other borderline malignant
      mesenchymal tumours, where rings and giant markers are alternative vehicles for
      amplified material.

PMID- 10072162
TI  - Modulation by phytochemicals of cytochrome P450-linked enzyme activity.
AB  - Compounds derived from plant sources with putative anticancer properties were
      studied for their effects on alkoxyresorufin O-dealkylase activity, a measure of
      cytochrome P450 activity. The phytochemicals investigated included benzyl
      isothiocyanate, caffeic acid, chlorogenic acid, diosmin, ferulic acid, indole-3
      carbinol, phenethyl isothiocyanate and resveratrol. Each phytochemical at
      concentrations of 0.25 and 0.5 microM was incubated with 0.2 mg hamster liver
      microsomal protein and 0.5 microM concentrations of benzyloxyresorufin,
      ethoxyresorufin and methoxyresorufin. Three of the phytochemicals tested, namely
      benzyl isothiocyanate, phenethyl isothiocyanate and resveratrol, exhibited potent
      inhibition of alkoxyresorufin O-dealkylase activity. Benzyl isothiocyanate
      inhibited benzyloxyresorufin O-dealkylase (BROD) activity, ethoxyresorufin O
      deethylase (EROD) activity and methoxyresorufin O-demethylase (MROD) activity by
      90% at both the 0.25 and 0.5 microM concentrations. Phenethyl isothiocyanate
      inhibited BROD activity by 69%, EROD activity by 90% and MROD activity by 94% at
      both concentrations tested. Resveratrol inhibited BROD activity by 69% at the
      0.25 microM concentration and by 78% at the 0.5 microM concentration. It
      inhibited EROD activity by 60% at the 0.25 microM concentration and by 80% at the
      0.5 microM concentration. Resveratrol exhibited the greatest inhibitory action
      toward MROD, i.e. 76% and 84% at the two concentrations tested. Chlorogenic acid
      significantly affected BROD, EROD and MROD activity only at the 0.5 microM
      concentration inhibiting by 51%, 47% and 54%, respectively. Caffeic acid affected
      BROD and MROD activity at 0.5 microM only inhibiting BROD activity by 46% and
      MROD activity by 40%. Diosmin inhibited EROD activity by 11% at the 0.25 microM
      concentration and by 61% at 0.5 microM. It inhibited MROD by 47% and 54% at the
      two concentrations tested but did not significantly alter BROD activity. Ferulic
      acid significantly inhibited EROD and MROD activity at the 0.5 microM
      concentration by 28% and 32%, respectively. Indole-3-carbinol significantly
      inhibited BROD activity by 26% at 0.25 microM and by 42% at 0.5 microM. It
      inhibited EROD and MROD activity by 28% and 29% at 0.5 microM, respectively. The
      alkoxyresorufin O-dealkylase reactions are selective for various isoforms of
      cytochrome P450. Our results suggest that the phytochemicals we tested have
      varied effects on the enzymatic activity of isoforms of cytochrome P450 that
      dealkylate benzyloxyresorufin, methoxyresorufin and ethoxyresorufin and therefore
      may have varied effects on the metabolism of substrates for these isoforms.

PMID- 10072163
TI  - Inhibition of colonization and cell-matrix adhesion after nm23-H1 transfection of
      human prostate carcinoma cells.
AB  - A human gene, nm23-H1, has been known as a metastasis suppressor in many tumor
      cells. The cellular mechanisms by which the nm23-H1 protein may directly or
      indirectly modulate the metastatic phenotype are not yet known. In this study the
      phenotypic effect of transfection of nm23-H1 cDNA into the human DU 145 prostate
      carcinoma cell line was examined. Despite similar growth rates, the nm23-H1
      transfected lines displayed decreased colonization in soft agar and adhesion to
      extracellular matrix components when compared with the control transfected line.
      The results suggest that the nm23-H1 gene product suppresses the metastatic
      potential of prostate carcinoma cells by inhibiting their ability in anchorage
      independent growth and extracellular matrix adhesion.

PMID- 10072164
TI  - Selectins induced by interleukin-1beta on the human liver endothelial cells act
      as ligands for sialyl Lewis X-expressing human colon cancer cell metastasis.
AB  - We have previously reported that colon cancer cells metastasized to the liver
      expressed an increased amount of sialyl Lewis X (SLeX) antigen compared to their
      corresponding primary lesions. It is now well known that SLeX antigen and sialyl
      Lewis A (SLeA) antigen are ligands for the selectins expressed on the endothelial
      cells. Therefore, it is assumed that SLeX-rich colon cancer cells could be easily
      adhered to the endothelial cells that express selectins. In this report we have
      tried to induce selectin expression on the human liver sinusoidal endothelial
      cells and have examined the adhesion of SLeX-high or -low expressing colon cancer
      cells to the interleukin-1beta (IL-1beta)-treated liver specimens using Stamper
      Woodruff assay. These human colon cancer cells are termed KM12HX or KM12LX cells,
      respectively. A significantly increased number of KM12HX cells adhered to the IL
      1beta-treated liver specimens compared to KM12LX cells. The adhesion of KM12HX
      cells was inhibited by the pretreatment of tumor cells with anti-SLeX antibody or
      by the pretreatment of liver specimens with anti-selectin antibodies. Selectin
      expression on the liver sinusoidal endothelial cells and endothelial cells of
      blood vessels after IL-1beta treatment was confirmed by immunohistochemically
      using anti-selectin monoclonal antibodies (MAbs). These findings strongly suggest
      that SLeX-expressing cancer cells could adhere to the sinusoidal endothelial
      cells via an SLeX-selectin interaction system and this could be a first step for
      colon cancer cells that metastasize to the liver. The mechanism by which these
      selectins can be induced in vivo is the next problem to be considered.

PMID- 10072165
TI  - The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes quiescent but
      not proliferating MG-63 human osteosarcoma cells to radiation.
AB  - Recent genetic and biochemical studies indicate that DNA-dependent protein kinase
      (DNA-PK) plays an important role in DNA double-strand break (dsb) repair and
      V(D)J recombination. Since the catalytic subunit of DNA-PK (DNA-PKcs) has high
      sequence homology with phosphatidylinositol 3-kinase (PI 3-kinase), we examined
      the effect of wortmannin, a specific inhibitor of PI 3-kinase, on the survival of
      human tumor cells after X-irradiation. The present study demonstrates that
      wortmannin at 20 microM is an effective radiosensitizer of quiescent (Q), but not
      proliferating (P) cells. In addition, the rejoining of DNA dsb is significantly
      inhibited in Q, but not in P cells. Finally, we found that Q cell extracts have
      approximately five-fold less DNA-PK activity than those of P cells. After a 2 h
      exposure to wortmannin, the DNA-PK activity of Q cell extracts was considerably
      lower than that of P cells. This can explain why wortmannin sensitizes Q, but not
      P cells to radiation.

PMID- 10072166
TI  - Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and
      in hamsters.
AB  - One of the diverse biological activities of triptolide, a diterpene from
      Tripterygium wilfordii, is its antitumor effect. We recently reported its in
      vitro cytotoxicity against several cultured tumor cell lines. Limited
      availability of purified fraction has prevented detailed investigation on its
      antitumor activity. In the present study, we showed by in vitro cytotoxicity
      assay and in vivo inhibition of tumor growth in hamsters that the triptolide was
      also highly effective against cholangiocarcinoma, a highly fatal tumor
      predominantly occurring in developing countries. Its ED50 for these hamster
      cholangiocarcinoma cell lines was found to be as low as 0.05 microg/ml. The
      compound was highly potent in the induction of apoptotic death in these tumor
      cells. DNA fragmentation and disintegrating apoptotic cells could be observed
      within 24 h of exposure to 0.5 microg/ml triptolide. The compound was tested
      against the growth of cholangiocarcinoma in a hamster model. A significant growth
      inhibition (P < 0.05) was noted in triptolide-treated hamsters (each of the 10
      animals received 10 injections for a total of 1.2 mg/animal). At the time of
      sacrifice 1 month after the initial injection, the mean tumor mass of the treated
      group was only 20-25% of that of the control group.

PMID- 10072167
TI  - Suppressive effects of estradiol on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated
      transcriptional activation of murine Cyp1a-1 in mouse hepatoma Hepa 1c1c7 cells.
AB  - Cultured mouse hepatoma Hepa lclc7 cells were treated with either estradiol or
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or in combination to assess the role
      of estradiol in the process of Cypla-1 induction. Estradiol at a concentration as
      high as 1 microM slightly increased the activity of Cypla-1-specific 7
      ethoxyresorufin O-deethylase (EROD); in contrast, TCDD-induced EROD activity and
      Cypla-1 mRNA levels were markedly reduced in the concomitant treatment of TCDD
      and estradiol in a dose-dependent manner. Treatment with tamoxifen, an anti
      estrogen which acts through the estrogen receptor, did not affect the suppressive
      effects of estradiol on TCDD-induced EROD activity. Electrophoretic mobility
      shift assay using nuclear extract of cells revealed that estradiol reduced
      transformation of the Ah receptor to the form capable of specifically binding to
      an oligonucleotide containing dioxin-response element (DRE) sequence. Consistent
      with this, estradiol decreased TCDD-induced increased chloramphenicol
      acetyltransferase (CAT) activity from a DRE-containing CAT reporter plasmid after
      transient transfection into the cells. The levels of the cytosolic [3H]TCDD-Ah
      receptor complex were reduced by estradiol in competitive Ah receptor binding
      assay using [3H]TCDD. This study demonstrated that estradiol acts as an
      antagonist to TCDD and can regulate Cyp1a-1 expression in an Ah receptor
      dependent manner but not through estradiol receptor in Hepa 1c1c7 cells.

PMID- 10072168
TI  - Antagonistic interactions of an arsenic-containing mixture in a multiple organ
      carcinogenicity bioassay.
AB  - Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and
      trichloroethylene (TCE) are frequently identified as groundwater contaminants
      near hazardous waste disposal sites. While the carcinogenicity of each of these
      chemicals has been extensively studied individually, little information exists
      regarding their carcinogenic potential in combination. Therefore, we investigated
      the carcinogenic promoting potential of chemical mixtures containing arsenic,
      DCE, VC and TCE following multiple initiator administration in a multiple organ
      carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay
      for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.),
      Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57,
      Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of
      this four-chemical mixture on the development of preneoplastic hepatic lesions
      (altered hepatocellular foci and glutathione S-transferase pi positive foci) as
      well as bronchioalveolar hyperplasia and adenoma formation.

PMID- 10072169
TI  - Detection of histo-blood group ABO mRNA in human chronic myeloid leukemia cell
      lines using reverse transcription-polymerase chain reaction (RT-PCR).
AB  - ABH carbohydrate antigens are cell surface carbohydrates which occur in three
      allelic forms, namely A, B and O blood groups. It is unknown how the ABO blood
      group is expressed in hemopoietic stem cells. In an attempt to verify the ABO
      mRNA expression in hemopoietic precursor cells, mRNAs were isolated from human
      chronic myeloid leukemia (CML) cell lines which are believed to be at the most
      immature level of hemopoietic differentiation among hemopoietic malignancies. In
      particular, K-562 and KOPM-28 cells were used with the reverse transcription
      polymerase chain reaction (RT-PCR) technique for amplifying ABO gene transcripts.
      The amplified ABO cDNAs from two cell lines were characterized by the digestion
      of Kpn-I restriction enzyme. The blood types were determined by polymerase chain
      reaction of the specific allele (PASA) method. Both of the human chronic myeloid
      leukemia cell lines expressed ABO mRNA. The quantity of ABO mRNA in the K-562
      cell line is significantly higher than that of the KOPM-28 cell line. The ABO
      blood type of these two cell lines was type O. Because the CML cell lines are
      presumed to be at the immature stem cell level of hematopoietic cell
      differentiation and because it is believed that the cultured cell lines from
      hematologic malignancy reflect the characteristics of normal corresponding
      hemopoietic cells, the hemopoietic stem cells should express mRNA of the ABO
      blood group.

PMID- 10072170
TI  - Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in
      colorectal carcinomas.
AB  - The DR5/TRAIL receptor 2 gene is a novel TNF receptor family member and induces
      apoptosis by overexpression of its product. DR5 is located on chromosome 8p21,
      where allelic deletions are often observed in advanced colorectal cancers. This
      evidence led us to examine whether or not mutations of the DR5 gene exist in
      these tumors. We determined the genomic structure of DR5, which consists of nine
      exons. DR5 has two alternatively spliced isoforms. All seven colorectal cancer
      (CRC) cell lines examined expressed the longer isoform predominantly. No somatic
      mutation was found in 41 CRC cases. Loss of heterozygosity of DR5 was found in
      nine (52.9%) of the 17 informative cases, which is similar to the previously
      reported frequencies observed for 8p21-22 in colorectal cancers. These findings
      suggest that inactivation of the DR5 gene may play only a small role, if any, in
      colorectal tumorigenesis.

PMID- 10072171
TI  - Mitogenic activity of steroidogenesis-inducing protein (SIP) during hypoxic
      stress of human ovarian carcinoma cells.
AB  - Steroidogenesis-inducing protein (SIP) is a novel growth factor isolated from
      human ovarian follicular fluid. While the steroidogenic and mitogenic effects
      appear to be restricted towards gonadal cell types, we have recently demonstrated
      that SIP is also a potent mitogen for cell lines derived from ovarian surface
      epithelial carcinomas. Here, we demonstrate that SIP reverses hypoxia-induced
      cell proliferation arrest of the human ovarian carcinoma cell line SKA, as
      determined by flow cytometry and cell proliferation assays. Concomitant with this
      reversal of proliferation arrest is an increase in expression of cyclins D and E
      and a reduction in expression of the cyclin-dependent kinase inhibitor p27.
      Pretreatment of hypoxic SKA cells with SIP is also shown to increase Taxol
      sensitivity of these cells by two-fold. These studies further characterize the
      mitogenic activity of SIP at the molecular level and suggest that this protein
      may be an effective biological response modifier for ovarian carcinoma cells.

PMID- 10072172
TI  - Retention of intracellular fibronectin expression in primary and metastatic
      thyroid carcinoma: an immunohistochemical study.
AB  - We previously showed that thyroid carcinoma distinctively expresses intracellular
      fibronectin (FN) compared to other carcinomas. To determine the persistency of
      such FN accumulation in metastasis, we immunohistochemically examined the
      accumulation of intracellular FN in 92 cases of different carcinomas originating
      from the thyroid gland, lung and kidney, 44 of which showed metastasis to other
      organs. In all of the cases, normal epithelial cells adjacent to carcinomas did
      not show intracellular FN. Almost all of the cases (31/32) of thyroid carcinoma
      with/without metastasis to the lung and/or kidney showed intracellular FN in both
      the primary and metastatic lesions. Few cases (2/38) of lung carcinoma and none
      of the 22 cases of kidney carcinoma showed intracellular FN in the primary and
      metastatic lesions. In conclusion, the intracellular accumulation of FN acquired
      after carcinogenic transformation is not a common phenomenon in carcinomas, but
      rather is distinctive for thyroid carcinoma, even when it metastasizes to other
      organs. The immunohistochemical detection of intracellular FN may be useful for
      diagnosing thyroid carcinoma, even in metastatic lesions.

PMID- 10072173
TI  - Image-guided core breast biopsy: a suitable method for preoperative biological
      characterization of small (pT1) breast carcinomas.
AB  - Multiple prognostic indicators, namely histological grade and immunostaining for
      estrogen (ER) and progesterone receptors (PgR), MIB 1, bc1-2, and p53, were
      retrospectively determined on preoperative core biopsies from 75 patients with pT
      1 breast carcinoma. The association of the preoperatively evaluated factors with
      those on the corresponding resected tumors (i.e. nodal status, histological
      grade, presence or absence of vascular invasion and necrosis) was assessed. In
      univariate analysis, histological grade on resected tumors was significantly
      associated with histological grade on core biopsy, p53 expression, MIB1
      immunostaining. An inverse association was found between postoperative histologic
      grade and ER, PgR, and bc1-2. Necrosis was significantly associated with grade,
      p53, MIB1, and inversely with ER, PgR, and bc1-2. Nodal involvement and vascular
      invasion were significantly associated with MIB1. In multivariate analysis,
      histological grade and ER were the only independent core biopsy variables
      associated with postoperative histological grade and necrosis, respectively. This
      study showed that image-guided core biopsy is a suitable method that can be used
      to reveal some characteristics of the tumor biology in a preoperative stage.

PMID- 10072174
TI  - Radiation-induced breakpoint misrejoining in human chromosomes: random or non
      random?
AB  - PURPOSE: To investigate whether radiation-induced misrejoining of chromosome
      breakpoints is randomly or non-randomly distributed throughout the human genome.
      MATERIALS AND METHODS: Data were combined from as many published cytogenetic
      studies as possible. The percentage of radiation-induced breaks per megabase (Mb)
      of DNA between all human chromosomes was calculated, and the observed and
      expected numbers of breakpoints based on DNA content between and within
      chromosomes were compared. RESULTS: A DNA-proportional distribution of
      breakpoints in 14 autosomes and a statistically significant deviation from
      proportionality in the other eight autosomes and the sex chromosomes was found.
      Regression analysis showed no significant change in breakpoint frequency per Mb
      of DNA relative to autosome size. Analysis between chromosome arms showed a non
      random distribution of induced breakpoints within certain autosomes, particularly
      the acrocentrics. In cases of non-random distributions, a prevalence of events
      was found at heterochromatic regions and/or telomeres, and a clustering of
      breakpoints was found near the centromeres of many chromosomes. CONCLUSIONS:
      There is an approximately linear proportionality between autosomal DNA content
      and observed breakpoint number, suggesting that subsets of autosomes can be used
      to estimate accurately the overall genomic frequency of misrejoined breakpoints
      contingent upon a carefully selected subset. However, this conclusion may not
      apply to the sex chromosomes. The results also support the influence of chromatin
      organization and/or preferential DNA repair/misrejoining on the distribution of
      induced breakpoints. However, these effects are not sufficient at a global level
      to dismiss the value of cytogenetic analysis using a genome subset for
      biodosimetry.

PMID- 10072175
TI  - Importance of DNA damage in the induction of apoptosis by ionizing radiation:
      effect of the scid mutation and DNA ploidy on the radiosensitivity of murine
      lymphoid cell lines.
AB  - PURPOSE: To study the effects of the murine scid mutation and DNA ploidy on the
      susceptibility of lymphoid cell lines to induction of apoptosis by ionizing
      radiation and thereby to determine whether DNA lesions are critical initiators of
      apoptosis. MATERIALS AND METHODS: Sensitivity to killing and rapidity of
      induction of apoptosis following y-irradiation or DNA-associated 125I decays were
      compared in pre-B and pre-T cell lines derived from wild-type mice and from mice
      homozygous or heterozygous for the scid mutation. Effects of differences in DNA
      ploidy on the same endpoints were studied using pseudo-diploid and -tetraploid
      clones of a murine pre-T cell line. RESULTS: Pairs of pre-B- and pre-T cell
      derived lines that expressed wild-type p53 and underwent rapid interphase
      apoptosis after irradiation were identified. In both cases, the scid homozygous
      cell lines were more sensitive to killing, suggesting that DNA repair capability
      influences susceptibility to induction of apoptosis. Increasing DNA ploidy in a
      cell line that undergoes rapid interphase apoptosis produced a corresponding
      increase in the number of DNA lesions required to produce a lethal event; again
      consistent with DNA being the target for radiation action. CONCLUSION: DNA damage
      is an important, if not the sole, initiator of external beam ionizing radiation
      induced apoptosis.

PMID- 10072176
TI  - Attenuation of caspase-3-dependent apoptosis by Trolox post-treatment of X
      irradiated MOLT-4 cells.
AB  - PURPOSE: The relationship between post-irradiation treatment with Trolox, an
      antioxidant that inhibits lipid peroxidation, and X-ray-induced apoptosis, with
      regard to signal transduction pathways, was examined in MOLT-4, a human leukaemia
      cell line. MATERIALS AND METHODS: In MOLT-4 cells treated with Trolox after X
      irradiation, viability, DNA fragmentation, expression of p53, BCL-2, BAX, active
      SAPK/JNK, active caspase-3 and the cleavage of PARP were measured by the trypan
      blue exclusion test, agarose gel electrophoresis and Western blotting. RESULTS:
      Stained cells and ladder-like DNA cleavage were observed after X-irradiation.
      Cell death and DNA fragmentation were significantly inhibited by the post
      irradiation treatment with Trolox. The expression of p53 and active SAPK/JNK was
      increased after X-irradiation, and fragments of PARP and the activated fragment
      of caspase-3 were produced. Post-irradiation treatment with Trolox attenuated the
      X-irradiation-induced expression, fragmentation or activation of these apoptosis
      related biomolecules. The expression of BCL-2 and BAX, which would occur
      downstream from p53, was not changed by irradiation and Trolox treatment.
      Furthermore, cell death was associated with caspase-3 because the ladder-like DNA
      cleavage was completely inhibited by Ac-DEVD-CHO but not Ac-YVAD-CHO, TLCK and
      PMSF. CONCLUSION: Post-irradiation events such as membrane damage induce caspase
      3-dependent apoptosis, which might be mediated by the activation of SAPK/JNK and
      be independent of p53.

PMID- 10072177
TI  - Biochemical indicators of whole-body gamma-radiation effects in the pig.
AB  - PURPOSE: Validation of the pig as an experimental animal model for dose
      assessment after ionizing irradiation. MATERIALS AND METHODS: The evolution of
      haematological and biochemical parameters was followed for up to 7 days after
      irradiation in pigs exposed to whole-body 60Co gamma-radiation at doses between O
      and 6 Gy. RESULTS: Some biochemical indicators showed significant variations:
      amylase, LDH, alkaline and acid phosphatases, ALT and iron. None of the studied
      parameters alone presents a reliable dose-effect relationship; however, there was
      evidence that the combination of lymphocyte and neutrophil counts and the
      determination of LDH, ALT, AST and urea levels allowed some dose determination,
      independent of time, if blood samples were taken within 7 days post-irradiation.
      CONCLUSION: The results confirm the main problems of biochemical dosimetry.
      However, the pig model could represent a useful alternative to the non-human
      primate in radiobiology research, especially in the case of partial-body
      exposure. A multiparametric approach to dose assessment seems to be possible in
      the pig model. Confirmation should be carried out using blood samples from
      patients undergoing radiotherapy treatment.

PMID- 10072178
TI  - Regional cholesterol synthesis in the intestinal mucosa of the genetically
      hypercholesterolaemic RICO rat: kinetic study following whole-body gamma
      irradiation.
AB  - PURPOSE: To investigate regional cholesterol synthesis and kinetics following
      whole-body gamma-irradiation in the genetically hypercholesterolaemic RICO rat.
      MATERIALS AND METHODS: Male RICO rats were fed a semi-purified diet for 1 month.
      At 10 weeks old they were exposed to gamma-irradiation (4 Gy, 1.5 Gy/min)
      together with controls. At intervals from 1-8 days after irradiation an
      intraperitoneal administration of [1-14C] acetate was given in order to estimate
      cholesterogenesis in mucosal cells located at different sites in the small
      intestine. The protein and DNA contents of the different enterocytes isolated
      along the crypt/villus axis in four equal parts of the intestine were also
      determined. RESULTS: A marked decrease of the mean quantities of cholesterol, DNA
      or protein in mucosa was seen 1 and 2 days after irradiation, showing the loss of
      30-40% of the intestinal epithelium. An overshoot of the cell amount was observed
      after 4 days with a return to basal values by 8 days after irradiation. The
      kinetic and topological evolution of cholesterol radioactivity, which reflects in
      situ cholesterol synthesis, showed a typical gradient in controls and at 8 days
      after irradiation. Cholesterogenesis decreased from the first to the third
      quarter of the small intestine (duodenum to proximal ileum), and then increased
      in the fourth quarter (distal ileum). In all segments of the small intestine,
      cholesterogenesis decreased from crypt cells to villus tip. At days 1 and 2 the
      gradient of cholesterogenesis on the villus was abolished. A slow recovery was
      seen from day 4 with a strong overshoot of cholesterol synthesis in crypt cells
      in every part of the small intestine. CONCLUSIONS: The RICO rat is a useful model
      for studying the effect of irradiation on regional cholesterogenesis in
      intestinal mucosa. Cholesterol synthesis in crypt cells was lowered 1 and 2 days
      after irradiation, over-expressed after 4 days and subsequently returned to its
      normal level.

PMID- 10072179
TI  - Long-term effects of X-irradiation on gastrointestinal function and regulatory
      peptides in monkeys.
AB  - PURPOSE: To investigate the long-term effects of X-irradiation on different
      aspects of gastrointestinal function in the non-human primate (Macaca mulatta).
      MATERIALS AND METHODS: Animals were exposed to X-radiation (5 or 6 Gy) or not
      (sham) and gastrointestinal function was investigated 4-6 years after exposure.
      Basal and agonist-stimulated short circuit current (Isc) responses were measured
      in isolated jejunum. Intestinal tissue was taken for histological analysis as
      well as for determination of mucosal marker enzyme activities and
      gastrointestinal regulatory peptide levels. Vasoactive intestinal peptide
      receptor characteristics were determined as well as VIP-stimulated Isc responses.
      GI peptides were also measured in plasma. RESULTS: Few differences were seen in
      basal electrical parameters or tissue morphology but there was a tendency for
      reduced basolateral membrane enzyme activity. VIP-stimulated Isc responses were
      reduced in irradiated animals as were VIP-stimulated adenylate cyclase responses.
      Plasma and tissue (ileal and colonic muscle layers) gastrin releasing peptide
      levels were increased in irradiated animals. In contrast circulating gastrin
      levels were lower. CONCLUSIONS: Late effects of total-body irradiation on GI
      function in monkeys showed altered circulating and tissue levels of some GI
      peptides. In addition the biological effects of vasoactive intestinal peptide
      were modified.

PMID- 10072180
TI  - Ornithine decarboxylase in organs of rat following chronic gamma-irradiation at
      low dose-rates.
AB  - PURPOSE: To investigate the consequence of continuous low dose-rate exposure to
      gamma-rays on ornithine decarboxylase (ODC EC 4.1.1.17) activity in organs of
      rat. MATERIALS AND METHODS: Young male Wistar rats were irradiated at 1.1, 2.1
      and 12.9 cGy/day in the dose ranges of 9-165, 17-315 and 100-2000 cGy,
      respectively, in a specially designed chamber. ODC activity was determined in
      20000 g supernatant fluid of thymus, spleen and lung by measuring the release of
      14CO2 from L-[1-14C]ornithine. RESULTS: Chronic y-irradiation modulated ODC
      activity. It decreased at low cumulated doses (after 8 and 15 days of exposure).
      At longer periods after chronic irradiation (after 45 and 90 days), ODC activity
      was restored up to control levels despite increasing values of cumulated doses.
      On day 150 a similar increase in ODC activity in spleen 2.1 cGy/day and in lung
      at 12.9 cGy/day was observed. CONCLUSIONS: These studies showed a non-monotonic
      pattern of the 'dose-response' curve. The results were interpreted in terms of
      the triggering of a homeostatic system.

PMID- 10072181
TI  - Voltammetric measurement of blood nitric oxide in irradiated rats.
AB  - PURPOSE. To investigate the effect of blood nitric oxide (NO) as a mediator of
      the neurovascular syndrome in rats following gamma-irradiation. MATERIAL AND
      METHODS: Using a voltametric method together with a carbon fibre based sensor, NO
      measurements were carried out in sham-irradiated and irradiated animals either in
      blood from the abdominal aorta or in blood samples from the heart. RESULTS: In in
      vitro conditions, properties of the probe were not altered by the ionizing
      radiation. Significant increases of +17% and +25.6% were observed in the
      voltametric signal height at 90 min and 24 h respectively after a 15 Gy gamma-ray
      exposure. These effects were followed on days 3 and 4 by a progressive decrease
      in the signal height of 7% and 18% respectively. Dose-effect relationships were
      observed at 90 min and 24 h after exposure to gamma-rays in the range of 3-15 Gy.
      Finally, the NO dependence on the measured voltametric signal was controlled by
      using inhibitors of the NO synthase (NOS) and by performing nitrate assays.
      CONCLUSIONS: Specific blood NO voltametric measurements are possible. Functional
      changes associated with NO after gamma-ray exposure are discussed.

PMID- 10072182
TI  - Modified bile acid profiles in mixed neutron and gamma-irradiated pigs.
AB  - PURPOSE: To determine the effect of mixed neutron and gamma-irradiation on the
      bile acid pool, which may be a key factor in radiation-induced diarrhoea.
      MATERIALS AND METHODS: The bile duct of pigs was catheterized to derive bile over
      several experimental weeks, both before and after a 5.9 Gy neutron and gamma
      irradiation. After measurement of the volume and sampling, bile was returned to
      the pig via a duodenal catheter. Samples of bile were analysed by HPLC for their
      individual and total bile acid content. Blood samples were also collected for
      total bile acid determination. RESULTS: Bile flow was significantly decreased
      during the first 24h and after the fifth day post-irradiation. Whereas total bile
      acid concentration in bile was not altered, profiles of individual bile acids
      were significantly altered as early as the first post-irradiation day. Such
      modifications in these profiles resulted in a change of the properties of the
      bile acid pool. An increased proportion of dihydroxylated bile acids known to be
      more deleterious for the intestine was observed. CONCLUSIONS: Neutron and gamma
      irradiation leads to modifications of bile acid profiles, which may partly
      explain radiation-induced diarrhoea by a coherent physiopathological mechanism.

PMID- 10072183
TI  - Sustained enhancement of liposome-mediated gene delivery and gene expression in
      human breast tumour cells by ionizing radiation.
AB  - PURPOSE: To investigate whether irradiation improves the delivery and expression
      of liposome-DNA complexes in human breast tumour cells. MATERIALS AND METHODS.
      MDA-MB231 and MCF-7 human breast tumour cells were transfected with a liposomal
      SV40-luciferase complex and irradiated immediately after, at 24h after or 24h
      prior to transfection and in the presence or absence of serum. The amount of
      luciferase plasmid in the cell was evaluated after extraction by the Hirt
      procedure, while luciferase expression was measured using a luminescence assay.
      RESULTS: Ionizing radiation enhanced the liposome-mediated delivery and
      expression of the SV40-luciferase transgene in MDA-MB231 breast tumour cells both
      in the absence and presence of serum as well as in MCF-7 breast tumour cells.
      Improved transgene delivery and expression was observed at a clinically relevant
      dose of 2 Gy, and was dose-dependent over a dose range of 2-10 Gy. The effects of
      irradiation on transgene expression were observed with irradiation immediately
      prior to exposure of the cells to the liposome-transgene complex, with
      irradiation up to 24 h before or up to 24 h after initiation of exposure.
      CONCLUSIONS: Irradiation at 24 h prior to exposure of breast tumour cells to the
      liposome-transgene complex appears to be the optimal approach for enhancing
      transgene delivery and expression. These findings suggest that ionizing radiation
      could promote the utility of gene therapy in the treatment of breast cancer.

PMID- 10072184
TI  - The effect of microcolony size, at time of irradiation, on colony forming
      ability.
AB  - PURPOSE: To investigate the effect of irradiating microcolonies of various sizes
      on their subsequent ability to form colonies. MATERIALS AND METHODS: The location
      of individual HPV-G cells in tissue culture flasks was recorded using
      computerized microscopy. This allowed the cells' positions to be continually
      revisited, which enabled manual sizing of individual microcolonies both at the
      time of irradiation (between 0-5 Gy) and following an incubation period during
      which the microcolonies were assessed for cologenic survival. RESULTS: The
      experiments indicate that when irradiated as microcolonies, cells have plating
      efficiencies (PE) that are lower than expected when compared with the prediction
      from the PE values of cells irradiated individually. CONCLUSION: These data
      support the conclusions of Mothersill and Seymour (1997b) which challenge the
      concept of independent survival of certain types of cells following irradiation.
      The results indicate that interactions between cells can occur even in small
      aggregates.

PMID- 10072185
TI  - Comparison of cell survival models for mixed LET radiation.
AB  - PURPOSE: Biophysical models for predicting survival for mixed LET radiations have
      been investigated by comparisons with experimental results from heavy ion
      irradiations. The aim was to choose a model for further theoretical studies on
      the effects of a variable RBE for protons. METHODS AND MATERIALS: Predicted
      survival curves by the Katz track-structure model, the linear quadratic model, LQ
      model, by Kellerer and Rossi and the lesion additivity model of Lam were compared
      to experimental survival curves for V79 cells that were irradiated with a mixture
      of nitrogen ions with an LET of either 78 or 165 keV/microm and 60Co gamma-rays.
      RESULTS: Results showed that all three models could predict survival within the
      uncertainty of the measurements for the different mixed radiation schedules used
      in this study. CONCLUSION: The choice of model could be made on other grounds,
      such as the type of model parameters and the availability of biological data for
      these parameters. Also, the possibility of including dose-rate effects and repair
      functions should be considered. For the purpose of carrying out theoretical
      studies on the effects of a variable RBE for protons, the LQ model was preferred.

PMID- 10072186
TI  - The effect of 2'-2' difluorodeoxycytidine (dFdC, gemcitabine) on radiation
      induced cell lethality in two human head and neck squamous carcinoma cell lines
      differing in intrinsic radiosensitivity.
AB  - PURPOSE: The present study investigated in vitro radio-enhancement by gemcitabine
      (dFdC) in two head and neck squamous cell carcinomas with different intrinsic
      cellular radiosensitivity. MATERIALS AND METHODS: Radiosensitive (SCC61,
      SF2=0.16) and radioresistant (SQD9, SF2=0.49) human head and neck squamous cell
      carcinomas were used. Confluent cells were incubated with dFdC and irradiated in
      drug-free medium with a single dose of 250 kV X-rays (0-12Gy). Cell survival
      curves were corrected for the toxicity of the drug alone. RESULTS: In both cell
      lines, radio-enhancement was observed with 5 microM dFdC incubated for 3 h prior
      to irradiation. Dose modification factors (DMF) at a surviving fraction level of
      0.5 reached 1.3 (95% CI 1.1-1.6) and 1.5 (95% CI 1.4-1.5) for SQD9 and SCC61
      cells, respectively. Radio-enhancement was associated with a modest increase in
      the alpha term of the linear-quadratic model. In SQD9 cells, radio-enhancement
      increased with dFdC incubation time. At 24h, DMF reached a value of 1.5 (95% CI
      0.9-3.2). In SCC61 cells at 24h, DMF reached a value of 1.1 (95% CI 0.9-1.2). In
      both cell lines, radio-enhancement increased with dFdC concentration up to 5-10
      microM from which values it levelled off up to 100 microM. CONCLUSIONS: The data
      indicated that dFdC induced a modest radio-enhancement in both cell lines. For a
      short incubation time, dFdC did not radio-enhance preferentially the more radio
      resistant cells, whereas the opposite was observed for a longer time. In both
      cell lines, radio-enhancement was saturated above a dFdC concentration of 5-10
      microM.

PMID- 10072187
TI  - Heat sensitivity of double-stranded DNA-dependent protein kinase (DNA-PK)
      activity.
AB  - PURPOSE: The heat sensitivity of DNA-PK activity in hybrid cells and the possible
      restoration of this activity with extracts from scid cells (defective in DNA
      PKcs), sxi-3 cells (defective in Ku80) and V794 (sxi-3 parental wild-type cells)
      was analysed. MATERIALS AND METHODS: Heat treatment of cells was performed in a
      water bath at 44 degrees C. The cell extract from scid cells or sxi-3 cells was
      added to heat-treated hybrid cell extracts, and the DNA-PK activity was assayed.
      RESULTS: When hybrid cells were heated at 44 degrees C for 15 min, DNA-PK
      activity was reduced to undetectable levels. The decreased DNA-PK activity could
      be restored in a concentration-dependent manner with the addition of scid cell
      extract. The sxi-3 cell extract could not restore heat-inactivated DNA-PK
      activity. CONCLUSIONS: DNA-PK was inactivated by heat treatment at 44 degrees C.
      Ku70/Ku80, but not Ku70 alone, could restore heat-inactivated DNA-PK.

PMID- 10072188
TI  - Radiation induced effects on cephalosporins: an ESR study.
AB  - PURPOSE: This paper reports experimental data on the ESR identification of four
      irradiated cephalosporins (cefpodoxime, cefsulodin, cefixime and ceftizoxime).
      MATERIALS AND METHODS: Equations to describe the ESR curves versus the dose and
      storage time were developed using mathematical procedures. RESULTS: Limits of
      detection (LOD) and limits of quantification (LOQ), estimated on the basis of the
      S/N ratios are 1.0+/-0.5 kGy and 2.5+/-0.5 kGy respectively. The yield of free
      radicals are in the range 4.6 10(19) - 2.2 10(20) radicals mol(-1) (G values from
      0.1 to 0.4). Besides a very unstable situation (cefsulodin), the time limit of
      detection of free radicals after storage ranges from about 1 year to over 2
      years. These time intervals are comparable with the shelf-life of the antibiotics
      and to the time limits found for 10 other cephalosporins described previously.
      Apart from qualitative detection, ESR spectrometry can be used for dose
      estimation. Exponential loss of ESR signal (first-order reaction) correlates well
      with the data. CONCLUSION: Given the sensitivity of ESR spectrometry, this
      experimental technique is promising for identification of irradiated
      cephalosporins.

PMID- 10072189
TI  - Mechanisms involved in the cellular calcium homeostasis in vascular smooth
      muscle: calcium pumps.
AB  - The regulation of cytosolic Ca2+ homeostasis is essential for cells, and
      particularly for vascular smooth muscle cells. In this regulation, there is a
      participation of different factors and mechanisms situated at different levels in
      the cell, among them Ca2+ pumps play an important role. Thus, Ca2+ pump, to
      extrude Ca2+; Na+/Ca2+ exchanger; and different Ca2+ channels for Ca2+ entry are
      placed in the plasma membrane. In addition, the inner and outer surfaces of the
      plasmalemma possess the ability to bind Ca2+ that can be released by different
      agonists. The sarcoplasmic reticulum has an active role in this Ca2+ regulation;
      its membrane has a Ca2+ pump that facilitates luminal Ca2+ accumulation, thus
      reducing the cytosolic free Ca2+ concentration. This pump can be inhibited by
      different agents. Physiologically, its activity is regulated by the protein
      phospholamban; thus, when it is in its unphosphorylated state such a Ca2+ pump is
      inhibited. The sarcoplasmic reticulum membrane also possesses receptors for 1,4,5
      inositol trisphosphate and ryanodine, which upon activation facilitates Ca2+
      release from this store. The sarcoplasmic reticulum and the plasmalemma form the
      superficial buffer barrier that is considered as an effective barrier for Ca2+
      influx. The cytosol possesses different proteins and several inorganic compounds
      with a Ca2+ buffering capacity. The hypothesis of capacitative Ca2+ entry into
      smooth muscle across the plasma membrane after intracellular store depletion and
      its mechanisms of inhibition and activation is also commented.

PMID- 10072190
TI  - Evaluation of serum uric acid changes in different forms of hepatic vascular
      inflow occlusion in human liver surgeries.
AB  - Uric acid values in serum have been analyzed as one of the markers to predict
      cellular damage due to ischemia reperfusion injury in the field of organ
      transplantation. The present study was conducted to confirm that uric acid values
      in serum could be an efficient marker of ischemic injury of liver parenchyma
      following hepatic vascular occlusion in human liver surgery. The changes in serum
      uric acid values were analyzed at fixed intervals during different liver
      surgeries. Significant increases in serum uric acid values were observed in
      patients who received the Pringle's maneuver in which hepatic vascular inflow was
      manipulated with a repetition of 15 min occlusion and 5 min perfusion, whereas
      almost no changes in uric acid values were found in both groups of patients who
      received the hemilobal occlusion of the Glisson's triad in which the right or
      left vessels were manipulated with a repetition of 30 min occlusion and 5 min
      perfusion and the "control method" in which the hepatic vessels of the lesion
      side were previously cut before liver resection. Uric acid values in serum
      increased in patients of Pringle's maneuver compared to those of the hemilobal
      occlusion of the Glisson's triad and the control method though these procedures
      were used in larger hepatectomies rather than Pringle's maneuver. The results
      indicated that serum uric acid values do not always reflect the severity of
      ischemia of the liver parenchyma but reflect intestinal congestion because marked
      intestinal congestion was observed in patients of Pringle's maneuver but not in
      patients of the hemilobal occlusion of the Glisson's triad and the control
      method. The evaluation of the severity of the ischemic injury of the liver should
      be done with caution when uric acid is used as a marker in human liver surgery.

PMID- 10072192
TI  - Inhibition of insulin metabolism by hydroxychloroquine and its enantiomers in
      cytosolic fraction of liver homogenates from healthy and diabetic rats.
AB  - To elucidate the mechanism by which hydroxychloroquine (HCQ) affects glucose
      metabolism, the effect of this drug and its enantiomers on insulin metabolism was
      studied using the cytosolic fraction of liver homogenates from healthy and
      diabetic rats. Eadie-Hofstee plots were monophasic suggesting that only a one
      component enzyme system is involved in insulin degradation in the fraction used.
      Reaction velocity (V) vs substrate concentration plots were consistent with a
      Vmax model. HCQ caused a significant reduction in Vmax and Vmax/Km values in both
      healthy (Vmax, 3.63 +/- 0.46 vs 1.97 +/- 0.13, ng/min/mg; protein P < 0.001; and
      Vmax/Km 0.265 +/- 0.015 vs 0.112 +/- 0.004, ml/min/g protein) and diabetic rats
      (Vmax, 0.718 +/- 0.06 vs 0.360 +/- 0.024, ng/min/mg protein; and Vmax/Km, 0.05 +/
      0.002 vs 0.023 +/- 0.001, ml/min/g protein). Significant reduction in the V was
      observed in the presence of racemic (rac)-, R-, or S-HCQ. Ranking of the
      inhibitory potency was HCQ > S = R except at highest examined concentration (20
      mg/mL) which was HCQ > S > R. In conclusion, the effect of HCQ on insulin
      degradation appears to be, in part, through inhibition of cytosolic insulin
      metabolizing enzyme. The effect is not stereoselective except at high
      concentrations. The R- and S-HCQ may have synergistic effects on inhibition of
      insulin degradation.

PMID- 10072191
TI  - Coenzyme Q10 supplementation and recovery from ischemia in senescent rat
      myocardium.
AB  - Many studies have suggested that parenteral administration of coenzyme Q10 (Q10)
      protects the myocardium of young experimental animals from post-ischemic
      reperfusion injury. Although parenteral administration, in contrast to per os
      supplementation, seems to elevate coenzyme Q concentrations in heart tissue, it
      is not suitable for prophylactic use. In addition, the incidence of ischemic
      events is greatest in older age. We studied the effect of Q10 supplementation on
      myocardial postischemic recovery in 18-month-old Wistar rats. The treated group
      (n=9) received 10 mg/kg/day of Q10 for 8 weeks in their chow while the normal
      chow of the control group (n=9) contained less than 0.5 mg/kg/day of Q10. The
      treatment clearly elevated plasma Q10 concentration (286 +/- 25 micromol/l and 48
      +/- 30 micromol/l, treated and controls, respectively, p<0.0001) but neither Q9
      nor Q10 concentrations in heart tissue were affected by the supplementation. The
      isolated perfused hearts were subjected to 20 minutes of ischemia and 30 minutes
      of reperfusion. The preischemic values of developed pressure (DP) but not
      contractility (+DP/delta t) and relaxation (-DP/delta t) were improved by Q10
      supplementation (p=0.034, p=0.057 and p=0.13, respectively) while in postischemic
      recovery no differences were observed between the groups (p>0.05 at all time
      points). Also, in myocardial flow, myocardial oxygen consumption (MVO2) and
      myocardial aerobic efficiency (DP/MVO2) the groups did not differ at any time
      points. Although dietary Q10 supplementation clearly elevated plasma Q10
      concentrations in senescent rats, the coenzyme Q contents in heart tissue and
      myocardial recovery from ischemia were not affected. However, it is possible that
      the site of action for the reported beneficial effects of Q10 is in the coronary
      endothelium rather than myocardium itself.

PMID- 10072193
TI  - Adrenoceptors modulate depressor responses of endothelin-1 into the superior
      colliculus of rats.
AB  - Endothelin-1 (ET-1) (10 pmol) microinjected into the superficial layer of
      superior colliculus induces decreases in blood pressure (control, 108 +/- 5 mmHg,
      n=6; ET-1, 71 +/- 4 mmHg, n=5). The effects on blood pressure induced by
      endothelin-1 were significantly (p<0.05) reduced by pre-administration into the
      superior colliculus of the alpha1-adrenoceptor agonist phenylephrine (1 nmol) (46
      +/- 5%, n=5), beta1-adrenoceptor antagonist acebutolol (5 nmol) (51 +/- 6%, n=5)
      or beta1/beta2-adrenoceptor antagonist propranolol (3.4 nmol) (51 +/- 11%, n=5).
      In contrast, endothelin-1-induced effects were increased (p<0.05) by
      microinjections into the superior colliculus of prazosin (2.4 nmol) (49 +/- 7%,
      n=5), an alpha1-adrenoceptor antagonist; dobutamine (4 nmol) (51 +/- 9%, n=5), a
      beta1-adrenoceptor agonist or isoprenaline (1 nmol) (49 +/- 6%, n=5), a
      beta1/beta2-adrenoceptor agonist. No involvement of alpha2- or beta2
      adrenoceptors has been detected. Therefore, ET-1 induces decreases in blood
      pressure with selective involvement of alpha1- and beta1-adrenoceptors.

PMID- 10072194
TI  - Reductions in binding and functions of D2 dopamine receptors in the rat ventral
      striatum during amphetamine sensitization.
AB  - Rats receiving amphetamine (5 mg/kg, i.p. once daily) for 14 continuous days
      develop behavioral sensitization to a subsequent amphetamine challenge (1 mg/kg)
      at withdrawal days 8 to 10. The present study was aimed at investigating whether
      there are changes in binding or functions of striatal D2 dopamine receptors in
      amphetamine-sensitized rats. The results indicated that the Bmax value of D2
      receptors in the ventral striatum decreased 40% and 52% 7 and 10 days after
      amphetamine withdrawal, respectively, without changes in their binding affinities
      (Kd). During this withdrawal period, the D(2/3) receptor agonist-induced (a)
      locomotor activation (bromocriptine, 5 mg/kg, i.p. or quinpirole, 1 mg/kg, i.p.)
      and (b) inhibition of forskolin-enhanced adenylyl cyclase activity
      (bromocriptine, 50 or 150 microM) in the ventral striatum were both suppressed as
      compared with saline controls. The decreases in D2 receptor function were
      unrelated to the coupled G-proteins, since none of the G alpha i-3, G alpha o or
      G alpha q in the ventral striatum exhibited quantitative differences between
      control and amphetamine sensitized rats. Collectively, these results demonstrate
      that intermittent amphetamine administration for a period of 14 days leads to
      diminished D2 receptor expression and functions in the ventral striatum at late
      withdrawal periods. The decrease of D2 receptors might reflect cellular
      mechanisms underlying the expression of amphetamine sensitization.

PMID- 10072195
TI  - Antinociceptive activity of impentamine, a histamine congener, after CNS
      administration.
AB  - The brain neuromodulator histamine induces antinociception when administered
      directly into the rodent CNS. However, several compounds derived from H2 and H3
      antagonists also produce antinociception after central administration.
      Pharmacological studies have shown that a prototype of these agents, improgan,
      induces analgesia that is not mediated by actions on known histamine receptors.
      Presently, the antinociceptive properties of a compound that chemically resembles
      both improgan and histamine were investigated in rats. Intraventricular (i.v.t.)
      administration of impentamine (4-imidazolylpentylamine) induced reversible, near
      maximal antinociception on the hot plate and tail flick tests (15 microg, 98
      nmol). The dose-response function was extremely steep, however, since other doses
      showed either no effect or behavioral toxicity. On the tail flick test,
      impentamine antinociception was resistant to antagonism by blockers of H1, H2, or
      H3 receptors, similar to characteristics previously found for improgan. In
      contrast, histamine antinociception was highly attenuated by H1 and H2
      antagonists. These findings suggest that: 1) the histamine congener impentamine
      may induce antinociception by a mechanism similar to that produced by improgan,
      and 2) additional histamine receptors may be discovered that are linked to pain
      attenuating processes.

PMID- 10072196
TI  - Involvement of c-myc and max in CNS beta-endorphin modulation of hepatic
      ornithine decarboxylase responsiveness to insulin in rat pups.
AB  - Previously, we have shown that subcutaneous administration of insulin stimulates
      ornithine decarboxylase (ODC) mRNA expression and enzymatic activity in the liver
      of infant control rats, but not in those pretreated intracerebroventricularly
      (i.c.v.) with beta-endorphin. This finding is consistent with the hypothesis that
      beta-endorphin synthesized in the brain plays a prime role in the control of
      postnatal development, in part, by modulating ODC gene transcription. We now
      report that insulin induced stimulation of hepatic ODC mRNA expression is
      accompanied by a concomitant increase in the expression of c-myc and max mRNAs,
      and that this effect is also inhibited by pretreatment with i.c.v. beta
      endorphin. These results suggest that CNS beta-endorphin suppresses tissue ODC
      responsiveness to trophic hormones by downregulating the expression of c-myc and
      max mRNAs, the encoded proteins of which are known to act physiologically as
      transcriptional activators of the ODC gene.

PMID- 10072197
TI  - Characterization of the nicotinic ligand 2-[18F]fluoro-3-[2(S)-2
      azetidinylmethoxy]pyridine in vivo.
AB  - The biodistribution of the nicotinic acetylcholine receptor (nAChR) radioligand 2
      [18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([18F]fluoro-A-85380, half-life
      of fluorine-18 = 110 min) in selected rat brain areas was assessed in vivo. The
      radiotracer showed a good penetration in the brain. The regional distribution of
      the radioligand was consistent with the density of nAChRs determined from
      previous studies in vitro. Sixty minutes post-injection, the highest uptake was
      observed in the thalamus, (1% I.D./g tissue), an intermediate one in the frontal
      cortex (0.78% I.D./g tissue), and the lowest in the cerebellum (0.5% I.D./g
      tissue). Pretreatment with several nAChR ligands (nicotine, cytisine,
      epibatidine, unlabeled fluoro-A-85380) substantially reduced uptake of the
      radioligand in the three cerebral areas. Pretreatment with the nAChR channel
      blocker mecamylamine or with the muscarinic receptor antagonist dexetimide had no
      appreciable effect on the uptake of fluoro-A-85380. These results support the
      high in vivo selectivity and specificity of fluoro-A-85380. Therefore,
      [18F]fluoro-A-85380 may be useful for positron emission tomography study of
      nAChRs in humans.

PMID- 10072198
TI  - Automatic construction of eigenshape models by direct optimization.
AB  - A new approach to the problem of automatic construction of eigenshape models is
      presented. Eigenshape models have proved to be successful in a variety of medical
      image analysis problems. However, automatic construction of eigenshape models has
      proved to be a difficult problem, and in many applications the models are built
      by hand-a painstaking process. We show that the fundamental problem is a choice
      of the correct pose and parametrization of each shape in the training set.
      Eigenshape models are not invariant under reparametrizations and pose
      transformations of the training shapes. Since there is no a priori correct choice
      for the pose and parametrization of each shape, their value should be chosen so
      as to produce a model that is compact and specific. This problem can be solved by
      finding an objective function that measures these properties and varying the pose
      and parametrization of each shape to optimize this function. We show that the
      appropriate objective function is the determinant of the covariance matrix. We go
      on to show how this objective function can be optimized by a genetic algorithm
      (GA) and thus give a practical method for building eigenshape models. The models
      produced are often better than hand-built ones. The advantages of a GA over other
      choices of optimization method are that no assumptions about the nature of the
      shapes being modelled is required and that the global minimum of the objective
      function can, in principle, be found.

PMID- 10072199
TI  - Semiautomatic segmentation of brain exterior in magnetic resonance images driven
      by empirical procedures and anatomical knowledge.
AB  - This work demonstrates encouraging results for increasing the automation of a
      practical and precise magnetic resonance brain image segmentation method. The
      intensity threshold for segmenting the brain exterior is determined automatically
      by locating the choroid plexus. This is done by finding peaks in a series of
      histograms taken over regions specified using anatomical knowledge. Intensity
      inhomogeneities are accounted for by adjusting the global intensity to match the
      white matter peak intensity in local regions. Automated results are incorporated
      into the established manually guided segmentation method by providing a trained
      expert with the automated threshold. The results from 20 different brain scans
      (over 1000 images) obtained under different conditions are presented to validate
      the method which was able to determine the appropriate threshold in approximately
      80% of the data.

PMID- 10072200
TI  - Ultrasonic and elasticity imaging to model disease-induced changes in soft-tissue
      structure.
AB  - Ultrasonic techniques are presented for the study of soft biological tissue
      structure and function. Changes in echo waveforms caused by microscopic
      variations in the mechanical properties of tissue can reveal disease mechanism,
      in vivo. On a larger scale, elasticity imaging describes the macroscopic
      mechanical properties of soft tissues. We summarize the approach and present
      preliminary results for studying disease-induced changes in renal tissue using
      these two acoustic imaging techniques.

PMID- 10072201
TI  - Cardiac material markers from tagged MR images.
AB  - Tagged magnetic resonance imaging (MRI) has shown great promise in non-invasive
      analysis of heart motion. To replace implanted markers as a gold standard,
      however, tagged MRI must be able to track a sparse set of material points, so
      called material markers, with high accuracy. This paper presents a new method for
      generating accurate motion estimates over a sparse set of material points using
      standard, parallel-tagged MR images. Each tracked point is located at the
      intersection of three tag surfaces, each of which is estimated using a thin-plate
      spline. The intersections are determined by an iterative alternating projections
      algorithm for which a proof of convergence is provided. The resulting data sets
      are compatible with applications developed to exploit implanted marker data. One
      set of these material markers from a normal human volunteer is examined in detail
      using several methods to visualize the markers. Numerical results that include
      additional studies are also discussed. Finally, an error analysis is presented
      using a computer-simulated left ventricle for which material markers are tracked
      with an RMS error of approximately 0.2 mm for typical imaging parameters and
      noise levels.

PMID- 10072202
TI  - A three-component deformation model for image-guided surgery.
AB  - In image-guided surgery it is necessary to align preoperative image data with the
      patient. The rigid-body approximation is usually applied, but is often not valid
      due to tissue deformation. Non-rigid deformation algorithms have been applied to
      related, but not identical problems, such as atlas matching and surgery
      simulation. In image-guided surgery we have the additional information that the
      deformation is constrained by the physical properties of the different tissues.
      The most important properties that must be incorporated are the rigidity of bone,
      the unconstrained nature of fluid regions and the relatively smooth deformation
      of soft tissue. Hence, we have developed a simplified model of tissue deformation
      based on a three-component system. Rigid regions are constrained by the rigid
      body transformation and fluid regions are unconstrained. A number of energy
      models for deformable tissues have been compared. The model can be deformed using
      intraoperative data, in this case landmarks, using a technique similar to active
      contours. A novel strategy to avoid folding in the transformation is described.
      Our method was applied to MRI and CT data from a neurosurgery patient with
      epilepsy. Although the current implementation is only two dimensional, the
      initial results are promising. As the algorithm must ultimately run in or near
      'real-time' an improved implementation of the energy minimization is underway.
      This paper presents the problem of tissue deformation, which has received little
      attention in the literature and outlines the framework we have developed for
      tackling this difficult subject.

PMID- 10072203
TI  - Statistical image reconstruction methods for randoms-precorrected PET scans.
AB  - Positron emission tomography (PET) measurements are usually precorrected for
      accidental coincidence events by real-time subtraction of the delayed-window
      coincidences. Randoms subtraction compensates on average for accidental
      coincidences but destroys the Poisson statistics. We propose and analyze two new
      approximations to the exact log-likelihood of the precorrected measurements, one
      based on a 'shifted Poisson' model, the other based on saddle-point
      approximations to the measurement of probability mass function (PMF). The methods
      apply to both emission and transmission tomography; however, in this paper we
      focus on transmission tomography. We compare the new models to conventional data
      weighted least-squares (WLS) and conventional maximum-likelihood methods [based
      on the ordinary Poisson (OP) model] using simulations and analytic
      approximations. The results demonstrate that the proposed methods avoid the
      systematic bias of the WLS method, and lead to significantly lower variance than
      the conventional OP method. The saddle-point method provides a more accurate
      approximation to the exact log-likelihood than the WLS, OP and shifted Poisson
      alternatives. However, the simpler shifted Poisson method yielded comparable bias
      variance performance to the saddle-point method in the simulations. The new
      methods offer improved image reconstruction in PET through more realistic
      statistical modeling, yet with negligible increase in computation time over the
      conventional OP method.

PMID- 10072204
TI  - An approximate bootstrap technique for variance estimation in parametric images.
AB  - Parametric imaging procedures offer the possibility of comprehensive assessment
      of tissue metabolic activity. Estimating variances of these images is important
      for the development of inference tools in a diagnostic setting. However, these
      are not readily obtained because the complexity of the radio-tracer models used
      in the generation of a parametric image makes analytic variance expressions
      intractable. On the other hand, a natural extension of the usual bootstrap
      resampling approach is infeasible because of the expanded computational effort.
      This paper suggests a computationally practical, approximate simulation strategy
      to variance estimation. Results of experiments done to evaluate the approach in a
      simplified model one-dimensional problem are very encouraging. Diagnostic checks
      performed on a single real-life positron emission tomography (PET) image to test
      for the feasibility of applying the procedure in a real-world PET setting also
      show some promise. The suggested methodology is evaluated here in the context of
      parametric images extracted by mixture analysis; however, the approach is general
      enough to extend to other parametric imaging methods.

PMID- 10072205
TI  - A method for approximating the density of maximum-likelihood and maximum a
      posteriori estimates under a Gaussian noise model.
AB  - The performance of maximum-likelihood (ML) and maximum a posteriori (MAP)
      estimates in non-linear problems at low data SNR is not well predicted by the
      Cramer-Rao or other lower bounds on variance. In order to better characterize the
      distribution of ML and MAP estimates under these conditions, we derive a point
      approximation to density values of the conditional distribution of such
      estimates. In an example problem, this approximate distribution captures the
      essential features of the distribution of ML estimates in the presence of
      Gaussian-distributed noise.

PMID- 10072206
TI  - Effects of terbium on the cytotoxicity of cisplatin in FaDu human head and neck
      squamous cell carcinoma.
AB  - In this investigation, we report a relationship between the terbium (Tb3+)
      binding protein and the cytotoxicity of cisplatin in human head and neck cancer
      cells. In the FaDu cell line, the cytotoxic action of cisplatin was shown to be
      approximately six times more potent than the cytotoxicity of Tb3+. When cisplatin
      was combined with 80 microM Tb3+, the IC20 and IC50 values for cisplatin were
      reduced by 70% and 24%, respectively. The IC80 value, however, was increased by
      124%. The results suggest that the cytotoxicity of cisplatin is enhanced by Tb3+
      at low cisplatin concentrations. In agreement with previous studies, calcium and
      cisplatin were found to be mixed-type and noncompetitive inhibitors,
      respectively, of the Tb3+ -FaDu intensity. These findings imply that the receptor
      binding of Tb3+ can modulate the cytotoxic activity of cisplatin.

PMID- 10072207
TI  - Oncogene transgenic mice: an useful model to study in vivo the relationships
      between gangliosides and oncogenes.
AB  - Several studies have demonstrated that transfer of oncogenes in cultured cells
      reproducibly induces transmissible alterations in their ganglioside profile; the
      transfection of the same oncogene into different cell lines and the different
      localization of the oncogene product result in a different ganglioside
      expression. In the present study the modifications of the ganglioside pattern in
      mammary carcinomas induced in transgenic mice by the activated form of the rat
      neu oncogene have been investigated. Whereas control mammary tissues contain
      quite exclusively GM3, all neoplastic samples show a substantial decrease of this
      ganglioside, an accumulation in variable amount of GM3-derived species (GM1, GD3,
      GD1a, GD1b, GT and GQ) and the appearance of new, not yet identified, sialic acid
      containing molecules. Interestingly, three out of 10 tumors analyzed, even if
      histologically comparable to the others but with a larger dimension, show a
      significative difference as regard to the GM1, GD3 and GD1a content. Our data
      suggest that an activated oncogene may induce also in vivo a specific and
      transmissible alteration in the ganglioside pattern, but this distribution could
      be susceptible to further modifications during the tumor progression.

PMID- 10072208
TI  - Diagnostic value of ferritin in the differential diagnosis of malignant
      effusions.
AB  - The diagnostic value of ferritin in pleural effusions or ascites was studied in
      151 samples from 147 patients (four patients had both kind of effusions). Samples
      (99 pleural effusions, 52 ascites) were evaluated in 4 groups: benign transudate
      (27 cases), benign nontuberculous exudate (26 cases), tuberculous exudate (47
      cases) and malignant exudate (51 cases). Median ferritin levels in effusions were
      67 ng/ml, 805 ng/ml, 889 ng/ml, 998 ng/ml and median effusion/serum (E/S) ratios
      were 0.7. 2.0, 4.9, 3.2 respectively. There was a significant difference between
      the concentrations of ferritin in malignant (51 cases) and nonmalignant effusions
      (100 cases) (p < 0.001), but the specificity and positive predictive value were
      low (43% and 45% respectively). Ferritin levels in transudate group were
      significantly lower than those in the others (p < 0.001). However, ferritin
      concentrations in three exudate groups were similar (p > 0.05). When compared the
      all inflammatory effusions (malignant, tuberculous, nontuberculous inflammatory
      exudates) with noninflammatory effusions (transudate and exudate), we determined
      a significant difference (p < 0.001). CONCLUSIONS: 1) Elevated ferritin
      concentration in effusions is significant indicators of exudates; 2) It is not
      good a parameter to discriminate the malignant effusions from the benign ones; 3)
      They can be useful in the differential diagnosis of the inflammatory exudations
      from the noninflammatory ones.

PMID- 10072209
TI  - Sex hormone binding globulin inhibits strongly the uptake of estradiol by human
      breast carcinoma cells via a deprivative mechanism.
AB  - A controversy exists for many years about the role of sex hormone binding
      globulin (SHBG) in the uptake of estradiol by the cells. Using the estradiol
      sensitive human breast carcinoma cell line MCF-7 and SHBG isolated from human
      serum by a new method, we observed a strong inhibition of estradiol uptake. The
      inhibition was higher when the concentration of the hormone was low. On the other
      hand, there seemed to be a lag period in inhibition when the concentrations of
      SHBG were very low, followed by an exponential increase, when the concentration
      exceeded a critical value. The inhibitory activity was higher when SHBG was added
      before or along with estradiol in the cell culture, as well as when the
      incubation period was elongated, while was dramatically minimized by the presence
      of dihydrotestosterone. Despite the inhibition of estradiol uptake caused by
      SHBG, the distribution of the hormone in various cell components remained
      practically the same. In conclusion, all indications from experimental data seem
      to suggest a simple deprivative mechanism being responsible for the inhibitory
      activity of SHBG on estradiol uptake by MCF-7 cells in culture.

PMID- 10072210
TI  - Antioxidant potential of cancerous human kidney tissues.
AB  - Antioxidant potentials (AOP) of cancerous and noncancerous adjacent human kidney
      tissues from 12 patients were measured. AOP of the cancerous tissues was found to
      be significantly lower than that of noncancerous ones. However, tissue
      malondialdehyde (MDA) levels were significantly higher in the cancerous tissues
      compared with noncancerous ones. In the intra-correlation analysis, carried out
      between AOP and MDA levels, significant correlation was found in the cancerous
      tissues (r = 0.9) but no correlation observed in the noncancerous ones. In the
      inter-correlation analysis, negative correlation was found between AOP's of
      cancerous and noncancerous tissues (r = -0.49) and positive correlation between
      MDA levels (r = 0.51). Results suggest that antioxidant potential of cancerous
      kidney tissues is significantly reduced compared with noncancerous ones.
      Therefore, they expose to high oxidant stress and free radical-induced
      peroxidative attacks, the results of which are cellular deformations.

PMID- 10072211
TI  - In vitro repair synthesis of BCNU-induced DNA damage.
AB  - The nitrosoureas including BCNU are potent chemotherapeutic drugs and have been
      used extensively for treatment of brain tumors and other neoplasias but the
      mechanisms of action for the DNA lesions created and their repair are still
      unclear. We have recently determined the in vitro repair of BCNU-treated DNA with
      cellular extracts and with DNA modifying enzymes. BCNU not only caused an
      increase in breaks in plasmid DNA, but an increase in cross-linked DNA was also
      observed after restriction enzyme digestion followed by gel electrophoresis. When
      HeLa cell-extracts were incubated with BCNU-treated DNA, 5-10 fold increases in
      DNA repair synthesis were observed as compared with untreated control.
      Substantial increases in 5'OH and 3'OH sites of the breaks were also found in
      BCNU-treated DNA as determined by the 10-20 fold increases in labeling with T4
      DNA kinase and by endogenous polymerases, while the amount of ligatable sites
      were at a minimal. When the repair capacity of two glioma cell lines (UWR1 and
      UWR3) with differential BCNU sensitivity, and cells from a chromosomal breakage
      disease, Bloom's syndrome (BS), were assessed, the activities of the two glioma
      cells were about 20-30% of the normal lymphoblastoid cells and HeLa cells,
      whereas no difference was observed in BS cells. However, differential patterns of
      DNA bands were observed in the glioma samples suggesting cell-type specific
      capacities of repair synthesis. These data are in accordance with the concept
      that BCNU creates multiple DNA lesions and suggests different cell types may
      develop a variety of repair capabilities.

PMID- 10072212
TI  - Type B monoamine oxidase activity in human brain malignant tumors.
AB  - An increase of monoamine oxidase (MAO) activity was observed in Central Nervous
      System (CNS) malignant tumors, but the isoform responsible was not identify
      (Marcozzi et al., 1985). In the present work we report additional data in order
      to ascertain whether the type A or B MAO isoform is increased in some malignant
      human tumors of CNS. In the homogenated tissues the amine oxidase activity was
      determined by the chemiluminescent method, using different and specific
      substrates or inhibitors of MAO A and B and copper-dependent enzymes. 19 samples
      from 4 different types of tumors and relative peritumoral tissues were analysed.
      The highest activity of was imputable to type B MAO.

PMID- 10072214
TI  - Comparison of immediate and in-hospital results of conventional balloon and
      perfusion balloon angioplasty using intracoronary ultrasound.
AB  - Angiographic studies have demonstrated that perfusion balloon percutaneous
      transluminal coronary angioplasty (PTCA) may result in modestly improved luminal
      gains and fewer major dissections than conventional balloon PTCA. However,
      intracoronary ultrasound (ICUS), which is more sensitive than angiography in
      evaluating the incidence, extent, and severity of dissection, was not used. We
      randomized 48 patients with 54 coronary stenoses to conventional or perfusion
      balloon PTCA. Four 2-minute inflations were permitted with conventional balloon
      PTCA. Two 10-minute inflations were allowed with perfusion balloon PTCA.
      Quantitative coronary angiography and ICUS were performed before and after
      treatment. In-hospital clinical events were recorded. Conventional and perfusion
      balloon PTCA achieved similar improvements in lumen diameter (1.25+/-0.51 vs
      1.28+/-0.51 mm) and reductions in percent stenosis (-45+/-21% vs -44+/-15%) by
      quantitative coronary angiography. Comparable gains in lumen diameter (0.62+/
      0.39 vs 0.50+/-0.38 mm) and lumen area (2.70+/-1.96 vs 2.05+/-1.52 mm2) were
      observed on ICUS. Angiography demonstrated similar rates of any dissection (36%
      vs 21%) and major dissection (12% vs 7%). ICUS identified a similar incidence of
      any dissection (60% vs 76%) and type II dissection (52% vs 62%). The relative
      dissection area was also similar (9.2+/-5.6% vs 7.8+/-5.8%). One conventional
      balloon patient experienced postprocedural chest pain. No patient in either group
      died, or had myocardial infarction, abrupt closure, or urgent revascularization.

PMID- 10072213
TI  - A matched comparison of the combination of prehospital thrombolysis and standby
      rescue angioplasty with primary angioplasty.
AB  - This study sought to assess the rate of acute Thrombolysis In Myocardial
      Infarction (TIMI) trial grade 3 patency that can be achieved with the combination
      of prehospital thrombolysis and standby rescue angioplasty in acute myocardial
      infarction. No large angiographic study has been performed after prehospital
      thrombolysis to determine the 90-minute TIMI 3 patency rate in the infarct
      related artery. Hospital outcome and artery patency were compared to 170 matched
      patients treated with primary angioplasty. Prehospital thrombolysis was applied
      151+/-61 minutes after the onset of pain in 170 patients (56+/-12 years, 86%
      men), using recombinant tissue-type plasminogen activator, streptokinase, or
      eminase. Emergency 90-minute angiography was performed in every case. All
      patients in whom thrombolysis failed underwent rescue angioplasty. After
      thrombolysis alone, TIMI grade 3 flow in the infarct-related artery was observed
      in 108 patients (64%), TIMI grade 2 in 12 (7%), and TIMI grade 0 or 1 in 50
      (29%). Rescue angioplasty was successful in 47 of 50 attempts. Overall, TIMI 3
      patency was achieved in 91%, and additionally TIMI 2 flow in 7% of patients, an
      average of 113+/-39 minutes after thrombolysis and 55+19 minutes after admission.
      Therefore, < 2 hours after thrombolysis, only 2% of patients had persistent
      occlusion (TIMI 0 or 1) of the infarct-related artery. In-hospital mortality was
      4% overall (7 of 170), and 3% in the 155 patients in whom TIMI 3 was obtained
      during the acute phase. Severe hemorrhagic complications occurred in 14 patients
      (8%) with 2 fatal cerebral hemorrhages (7% of patients required transfusions).
      The matched comparison with primary PTCA showed no significant difference in
      hospital outcome. Combined prehospital thrombolysis, 90-minute angiography, and
      rescue angioplasty yield a high rate of acute TIMI 3 patency rate early after
      thrombolysis and hospital admission. A randomized, prospective comparison between
      these 2 reperfusion strategies may be now warranted.

PMID- 10072215
TI  - Economics, health-related quality of life, and cost-effectiveness methods for the
      TACTICS (Treat Angina With Aggrastat [tirofiban]] and Determine Cost of Therapy
      with Invasive or Conservative Strategy)-TIMI 18 trial.
AB  - Concern over escalating health care costs has led to increasing focus on
      economics and assessment of outcome measures for expensive forms of therapy. This
      is being investigated in the Treat Angina With Aggrastat [tirofiban] and
      Determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI
      18 trial, a randomized trial comparing outcome of patients with unstable angina
      or non-Q-wave myocardial infarction treated with tirofiban and then randomized to
      an invasive versus a conservative strategy. Hospital and professional costs
      initially and over 6 months, including outpatient costs, will be assessed.
      Hospital costs will be determined for patients in the United States from the UB92
      formulation of the hospital bill, with costs derived from charges using
      departmental cost to charge ratios. Professional costs will be determined by
      accounting for professional services and then converted to resource units using
      the Resource Based Relative Value Scale and then to costs using the Medicare
      conversion factor. Follow-up resource consumption, including medications, testing
      and office visits, will be carefully measured with a Patient Economic Form, and
      converted to costs from the Medicare fee schedule. Health-related quality of life
      will be assessed with a specific instrument, the Seattle Angina Questionnaire,
      and a general instrument, the Health Utilities Index at baseline, 1, and 6
      months. The Health Utilities Index will also be used to construct a utility. By
      knowing utility and survival, quality-adjusted life years will be determined.
      These measures will permit the performance of a cost-effectiveness analysis, with
      the cost-effectiveness of the invasive strategy defined and the difference in
      cost between the invasive and conservative strategies divided by the difference
      in quality-adjusted life years. The economic and health-related quality of life
      aspects of TACTICS-TIMI 18 are an integral part of the study design and will
      provide a comprehensive understanding of the impact of invasive versus
      conservative management strategies on a broad range of outcomes after
      hospitalization for unstable angina or non-Q-wave myocardial infarction.

PMID- 10072216
TI  - Importance of posterior chest leads in patients with suspected myocardial
      infarction, but nondiagnostic, routine 12-lead electrocardiogram.
AB  - Criteria for reperfusion therapy in acute myocardial infarction require the
      presence of ST elevation in 2 contiguous leads. However, many patients with
      myocardial infarction do not show these changes on a routine 12-lead
      electrocardiogram and hence are denied reperfusion therapy. Posterior chest leads
      (V7 to V9) were recorded in 58 patients with clinically suspected myocardial
      infarction, but nondiagnostic routine electrocardiogram. ST elevation >0.1 mV or
      Q waves in > or =2 posterior chest leads were considered to be diagnostic of
      posterior myocardial infarction. Eighteen patients had these changes of posterior
      myocardial infarction. All 18 patients were confirmed to have myocardial
      infarction by creatine phosphokinase criteria or cardiac catheterization. Of the
      17 patients who had cardiac catheterization, 16 had left circumflex as the
      culprit vessel. We conclude that posterior chest leads should be routinely
      recorded in patients with suspected myocardial infarction and nondiagnostic,
      routine electrocardiogram. This simple bedside technique may help proper
      treatment of some of these patients now classified as having unstable angina or
      non-Q-wave myocardial infarction.

PMID- 10072217
TI  - Mechanism by which quinapril improves vascular function in coronary artery
      disease.
AB  - Angiotensin-converting enzyme (ACE) inhibition has been shown to improve
      endothelium-dependent vasodilator responsiveness, but the contribution and
      mechanism of enhanced nitric oxide (NO) bioactivity to this effect in patients
      with coronary artery disease are unknown. We investigated the effect of ACE
      inhibition on brachial artery dilator responsiveness to increased shear stress
      after forearm ischemia by ultrasonography as a bioassay for endothelial NO
      available to vascular smooth muscle in 9 men with coronary artery disease. Serum
      nitrogen oxides were measured after 3 days of nitrate-restricted diet as an index
      of endothelial NO release. Patients received quinapril 20 to 40 mg/day for 8
      weeks. Relative to pretreatment measurements, quinapril increased flow-mediated
      dilation (from 2.4+/-0.4 to 10.8+/-2.2, p <0.001), with significant improvement
      persisting 1 week after discontinuation of therapy (6.7+/-2.5%, p <0.01).
      However, quinapril decreased serum nitrogen oxide levels by 19+/-17% compared
      with pretreatment values (from 58.2+/-19.0 to 46.0+/-13.3 micromol/L, p <0.01).
      Thus, ACE inhibitor therapy with quinapril selectively improves endothelium
      dependent vasodilator responsiveness by increased NO bioactivity in relation to
      vascular smooth muscle in patients with coronary artery disease, an effect
      achieved at a lower rate of NO release from the endothelium. These findings
      suggest that ACE inhibitors may reduce angiotensin II-induced oxidant stress
      within the vessel wall and protect NO from oxidative inactivation. This effect
      may reduce endothelial NO synthesis required for vasomotor regulation.

PMID- 10072218
TI  - Acute anti-ischemic effects of perindoprilat in men with coronary artery disease
      and their relation with left ventricular function.
AB  - Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic
      events in patients with coronary artery disease, but whether it protects against
      acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on
      potential anti-ischemic properties is unknown. We performed a double-blind trial
      in 25 patients with exercise-induced ischemia. The effects of perindoprilat on
      pacing-induced myocardial ischemia were examined. Fourteen patients received
      perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups
      were formed in the perindoprilat group: 7 patients with LV dysfunction (LV
      ejection fraction <0.40), and 7 patients with normal LV function. After receiving
      the study medication, the pacing test was repeated. During the first pacing test
      both groups developed ischemia. After perindoprilat administration, the increase
      in systemic vascular resistance and LV end-diastolic pressure were significantly
      blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac
      uptake of norepinephrine was inhibited by perindoprilat, and the increase in
      atrial natriuretic peptide was less pronounced; also, ST-segment depression was
      reduced by 32% compared with placebo (all p <0.05). In the group with LV
      dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67%
      and myocardial lactate production was prevented, but this did not happen in the
      group with normal LV function. In addition, the increase in arterial
      norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results
      indicate that perindoprilat reduced acute, pacing-induced ischemia in
      normotensive patients. In patients with (asymptomatic) LV dysfunction these
      effects were more pronounced than in patients with normal LV function.

PMID- 10072219
TI  - Vascular endothelial growth factor in acute Kawasaki disease.
AB  - Vascular endothelial growth factor (VEGF), also known as vascular permeability
      factor, is an important regulator of angiogenesis and blood vessel permeability.
      Kawasaki disease (KD) is characterized by systemic vasculitis with increased
      vascular permeability, implying a possible role of VEGF in KD. To elucidate the
      involvement of VEGF in the pathogenesis of KD, we investigated 30 patients with
      acute KD, comparing the time course of plasma VEGF levels (n = 123) with clinical
      symptoms and laboratory findings. Compared with control values, the peak levels
      of plasma VEGF were significantly elevated (38+/-26 vs 244+/-248 pg/ml, p
      <0.001). The VEGF levels at the appearance of skin rash and/or edema of hands and
      feet were also elevated to 176+/-163 pg/ml (p <0.001). In 7 patients (23%), the
      plasma VEGF levels remained increased after the resolution of the skin rash and
      peripheral edema. The VEGF levels were independent of gamma globulin therapy and
      levels of serum albumin and C-reactive protein. We also measured the plasma
      levels of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor
      alpha, both of which can upregulate VEGF in vitro. The plasma levels of VEGF were
      highly correlated with those of TGF-beta1 (n = 63, r = 0.73, p <0.001) but not
      with those of tumor necrosis factor alpha. These findings suggest that the
      production of VEGF is increased and may be upregulated by TGF-beta1 in acute KD.
      VEGF may be involved in the hyperpermeability of local blood vessels in acute KD.

PMID- 10072220
TI  - Dobutamine stress echocardiography at 7.5 mg/kg/min using color tissue Doppler
      imaging M-mode safely predicts reversible dysfunction early after reperfusion in
      patients with acute myocardial infarction.
AB  - Dobutamine stress echocardiography (DSE) is widely used to predict reversible
      left ventricular dysfunction, but evaluation by this method is subjective. The
      recently developed color tissue Doppler imaging (TDI) M-mode may permit objective
      and quantitative assessment of changes in wall motion induced by DSE. We tested
      the hypothesis that this new method can detect sensitively reversible dysfunction
      in the post-myocardial infarction setting. DSE with color TDI M-mode and
      conventional DSE were performed to predict reversible dysfunction in 53 patients
      at a mean of 3 days after infarction using 7.5 and 10 microg/kg/min of
      dobutamine. Follow-up regular echocardiography (4 weeks later) was used as the
      reference technique to define reversible dysfunction segments. To predict
      reversible dysfunction segments, the standard segmental wall motion score change
      on conventional DSE and the ratio of the segmental wall velocity difference at
      rest versus stress (7.5 and 10 microg/kg/ min) on DSE with color TDI M-mode (7.5
      TDI-M and 10-TDI-M, respectively) were used. With 7.5 microg/kg/min of
      dobutamine, the sensitivity for predicting reversible dysfunction using color TDI
      M-mode (7.5-TDI-M) was significantly higher than that of conventional DSE (89% vs
      73%, p <0.05) whereas specificities and predictive values were almost identical.
      With a 10-microg/kg/min dose, color TDI-M mode (10-TDI-M) and conventional DSE
      were not significantly different in predicting reversible dysfunction. With use
      of color TDI-M mode, regional wall motion during DSE was analyzed objectively and
      quantitatively. Moreover, combined TDI-M and conventional data were slightly
      superior to either mode alone. There were no arrhythmias during 7.5 microg/kg/min
      of dobutamine, but 9 arrhythmias occurred during the 10-microg/kg/min dose in
      patients with acute myocardial infarction. In conclusion, color TDI M-mode
      permits objective and quantitative assessment of regional ventricular wall motion
      and gives additional information for detecting reversible dysfunction in DSE.
      Improvement of sensitivity at a lower dose of dobutamine with color TDI-M mode
      may increase the safety of DSE in the post-myocardial infarction setting.

PMID- 10072221
TI  - Lewis blood group phenotype as an independent risk factor for coronary heart
      disease (the NHLBI Family Heart Study).
AB  - In the Copenhagen Male Study, men with Lewis blood group phenotype Le(a-b-) were
      found to have increased risk for coronary heart disease (CHD); such a relation
      has not been confirmed in men, and has not been evaluated in women. In the NHLBI
      Family Heart Study, we determined the Lewis blood type of 1,620 white subjects
      (790 male and 830 female subjects). The Lewis(a-b-) phenotype was found in 142
      subjects (8.8%), 6.3% of subjects from randomly chosen families and 9.7% of
      subjects from families found to be at high risk for CHD. A history of CHD was
      present in 39.1% of men with Le(a-b-) versus 27.2% of men with other Lewis types;
      for women, the corresponding numbers were 12.3% versus 9.4%, respectively. In
      multivariate analysis, adjusting for age, sex, and risk group, the odds ratio for
      CHD was 2.0 (95% confidence interval = 1.2 to 3.1) for Le(a-b-) versus other
      Lewis groups. Mean values for body mass index, blood pressure, total cholesterol,
      low-density lipoprotein and high-density lipoprotein cholesterol, glucose,
      insulin, homocysteine, and fibrinogen were not significantly different between
      Le(a-b-) subjects and others, but triglycerides (p = 0.002) were higher in the
      Le(a-b-) subjects. However, inclusion of all risk factors in multivariate
      analysis did not diminish the increased risk for CHD associated with the Le(a-b-)
      phenotype. We conclude that the Le(a-b-) phenotype is associated with an
      increased risk for CHD; its effect does not appear to act predominantly through
      conventional cardiovascular risk factors. At present, mechanisms of effect are
      unknown.

PMID- 10072222
TI  - Relation of induced to spontaneous ventricular tachycardia from analysis of
      stored far-field implantable defibrillator electrograms.
AB  - Predischarge testing of implantable cardioverter-defibrillators is often used to
      tailor antitachycardia pacing algorithms based on the response of induced
      ventricular tachycardia (VT) to pacing. Despite this practice, little is known
      about the relation between VT induced at predischarge study and VT that occurs
      spontaneously. To clarify this relation, we identified 19 patients with VT
      induced at predischarge study and compared the characteristics of the induced VT
      with the first episode of spontaneous VT. VT morphology, tachycardia cycle
      length, and response to antitachycardia pacing were measured from far-field
      electrograms stored by the implantable cardioverter-defibrillator. All subjects
      had coronary artery disease and previous myocardial infarction. The mean time
      from baseline study until a spontaneous VT episode was 162+/-121 days. Analysis
      of far-field electrograms revealed that spontaneous VT was morphologically
      different from predischarge-induced VT in 13 of 19 cases (68%). The cycle length
      of induced VT was significantly shorter than spontaneous VT when VT morphologies
      were different but not when spontaneous and induced VT had an identical
      morphology. Antitachycardia pacing was effective in terminating 18 of 19 (95%)
      induced VTs and 14 of 18 (78%) spontaneous VTs. Antitachycardia pacing was
      effective in terminating 9 of 12 episodes of morphologically different
      spontaneous VTs and 5 of 6 episodes of morphologically identical spontaneous VTs
      (p = NS). Thus, the characteristics of VT induced at predischarge study correlate
      poorly with those of subsequent spontaneous VT episodes due to the induction of
      faster "nonclinical" VTs at predischarge testing. This may limit the
      applicability of predischarge testing in tailoring antitachycardia pacing
      algorithms.

PMID- 10072223
TI  - JTc prolongation with d,l-sotalol in women versus men.
AB  - Women are at increased risk for torsades de pointes associated with a variety of
      drugs that prolong ventricular repolarization, but few data exist regarding
      possible sex differences in extent of repolarization changes with these
      medications. We sought to compare JTc interval responses in women and men during
      treatment with d,l-sotalol. The study cohort consisted of 1,897 patients (26%
      women) with available baseline and > or =1 on-drug electrocardiogram from a
      database involving patients exposed to oral d,l-sotalol without developing
      torsades de pointes. The mean lowest and highest daily d,l-sotalol dose,
      normalized for weight, was not significantly different between sexes. At each
      dosing extreme, on-drug JTc was significantly longer in women (p < or =0.0002).
      Statistically independent predictors of on-drug JTc included gender (p = 0.003),
      baseline JTc (p = 0.0001), dose (p = 0.0001), serum creatinine (p < or =0.03),
      and history of sustained ventricular tachyarrhythmias (p = 0.01). In both men and
      women, as baseline JTc increased, the drug-induced increment in JTc became
      progressively smaller. Thus, in response to d,l-sotalol, JTc intervals become
      longer in women than in men. This sex difference is independent of dose and not
      solely attributable to the known gender disparity in baseline JTc. The greater
      propensity of women to drug-induced torsades de pointes may represent the most
      extreme expression of a basic sex difference in the response to medications that
      prolong ventricular repolarization.

PMID- 10072224
TI  - A stepwise testing protocol for modern implantable cardioverter-defibrillator
      systems to prevent pacemaker-implantable cardioverter-defibrillator interactions.
AB  - Current use of newer implantable cardioverter-defibrillators (ICDs) has changed
      the spectrum of pacemaker-ICD interactions and provided new tools for testing and
      understanding those interactions. Testing for pacemaker-ICD interactions was
      performed in 31 procedures involving 22 patients. The protocol included: (1)
      evaluation of pacemaker stimulus artifact amplitude and its ratio to that of the
      evoked ventricular electrogram, (2) testing for inhibition of ventricular
      fibrillation (VF) detection by the ICD during asynchronous pacing at maximum
      output, (3) evaluation by pacemaker event marker recordings of pacemaker sensing
      behavior while programmed to nonasynchronous mode during ventricular tachycardia
      (VT) or VF, and (4) evaluation of postshock interactions. Inhibition of detection
      of VT/VF was found in 6 of 22 patients (27.2%). Large stimulus artifact amplitude
      (>2 mV) or stimulus artifact:evoked QRS ratio > 1/3 had a positive predictive
      accuracy of 18% and 14.4%, respectively, and a negative predictive accuracy of
      100% and 92.3%, respectively, for clinically significant interaction.
      Asynchronous pacing occurred in 16 of 31 procedures (51.6%), and was due to
      underdetection by the pacemaker in 4 of 16 (25%) and noise reversion in 12 of 16
      (75%). Postshock phenomena occurred in 6 cases, 3 of which were clinically
      significant. Overall, 11 of 22 patients (50%) had clinically significant
      interactions discovered by this protocol, which led to system revisions in 6 and
      to pacemaker output reprogramming in 5. Thus, pacemaker-ICD interactions are
      frequently detected using a thorough and systematic protocol. Most cases can be
      managed by system revision or pacemaker reprogramming.

PMID- 10072225
TI  - Relation of left ventricular hypertrophy and geometry to asymptomatic
      cerebrovascular damage in essential hypertension.
AB  - Increased left ventricular (LV) mass and abnormal geometry have a powerful
      prognostic value for cardiovascular morbidity and mortality including stroke.
      However, there have been no studies on the association between LV hypertrophy and
      preclinical brain damage in essential hypertensive patients. In the present
      study, we investigated the relation between LV hypertrophy and asymptomatic
      cerebrovascular damage identified by magnetic resonance imaging in 150 essential
      hypertensive patients, with an emphasis on LV geometry. Patients were divided
      into the following 4 groups according to their LV mass index and relative wall
      thickness; normal ventricular geometry (n = 50), concentric remodeling (n = 22),
      eccentric hypertrophy (n = 44), and concentric LV hypertrophy (n = 34). Lacunar
      lesions and leukoaraiosis were evaluated. The prevalence of lacunae was
      significantly higher in patients with LV remodeling than in patients with normal
      LV (chi-square 19.6, p = 0.0002). The number of lacunae was significantly higher
      in patients with LV hypertrophy than in patients with normal LV or concentric
      remodeling (F [3,146] = 8.03, p<0.0001). The severity of leukoaraiosis was also
      significantly greater in patients with LV hypertrophy than in patients with a
      normal left ventricle (chi-square 14.5, p = 0.02). Stepwise regression analysis
      confirmed that LV mass index and relative wall thickness, in addition to age and
      systolic blood pressure, were independent predictors for asymptomatic
      cerebrovascular damage, even in the absence of neurologic abnormalities. In
      hypertensive patients, LV hypertrophy, and especially concentric LV hypertrophy,
      provides important prognostic information on the presence of pre-clinical brain
      damage.

PMID- 10072226
TI  - Prognostic significance of exercise-induced systemic hypertension in healthy
      subjects.
AB  - Exercise hypertension has been suggested to predict future resting hypertension,
      but its significance in terms of cardiovascular risk has not been defined. To
      assess the prognostic significance of exercise hypertension, 150 healthy,
      asymptomatic subjects with normal resting blood pressures and exercise systolic
      blood pressures > or =214 mm Hg (i.e., >90th percentile) on Bruce treadmill tests
      were identified retrospectively and age- and gender-matched with subjects with
      exercise systolic blood pressures of 170 to 192 mm Hg (40th to 70th percentiles).
      Subjects were contacted by survey a mean of 7.7+/-2.9 years after the index
      treadmill test. The survey response rate was 93%. There were 12 deaths, including
      8 in the exercise hypertension group. A major cardiovascular event, defined as
      cardiovascular death, myocardial infarction, stroke, coronary angioplasty, or
      coronary bypass graft surgery occurred in 5 controls and 10 subjects with
      exercise hypertension. At follow-up, 13 controls and 37 subjects with exercise
      hypertension were now diagnosed as having resting hypertension. In multivariate
      analysis, exercise hypertension was not a significant predictor for death or any
      individual cardiovascular event, but was for total cardiovascular events and new
      resting hypertension. The multivariate risk ratio for exercise hypertension was
      3.62 (p = 0.03) in predicting a major cardiovascular event. Other significant
      predictors included body mass index and age. For predicting new resting
      hypertension, the multivariate odds ratio for exercise hypertension was 2.41 (p =
      0.02). These data suggest that exercise hypertension carries a small but
      significant risk for major cardiovascular events in healthy, asymptomatic persons
      with normal resting blood pressures.

PMID- 10072227
TI  - Cytokine network in congestive heart failure secondary to ischemic or idiopathic
      dilated cardiomyopathy.
AB  - Inflammatory cytokines may play a pathogenic role in the development of
      congestive heart failure (CHF). Elevated circulating levels of inflammatory
      cytokines have been reported in CHF, but most studies have focused on only a few
      cytokine parameters. However, the activity of these cytokines are modulated by
      soluble cytokine receptors and cytokines with anti-inflammatory activities, and
      in the present study several of these interacting factors were examined
      simultaneously in 38 CHF patients with various degrees of heart failure and in 21
      healthy controls. Patients with CHF had increased plasma concentrations of tumor
      necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble
      interleukin-6 receptor, glycoprotein (gp)130. They also had elevated ratios of
      TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as
      enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects.
      In addition to raised circulating levels of inflammatory cytokines, CHF patients
      with severe heart failure also had abnormalities in the levels of anti
      inflammatory cytokines, with decreased levels of transforming growth factor beta1
      and inadequately raised interleukin-10 in relation to the elevated TNFalpha
      concentrations. This dysbalance between inflammatory and anti-inflammatory
      cytokines was also found in monocyte supernatants from CHF patients. The
      abnormalities in the cytokine network were most pronounced in patients with the
      most severe heart failure, and several of the immunologic parameters, in
      particular soluble gp130, were correlated with variables reflecting deranged
      hemodynamic status. The present study analyzing the complexity of the cytokine
      network in CHF, demonstrates profound disturbances in the levels of both
      inflammatory and anti-inflammatory mediators with a marked dysbalance favoring
      inflammatory effects.

PMID- 10072228
TI  - Effects of low altitude on exercise performance in patients with congestive heart
      failure after healing of acute myocardial infarction.
AB  - Patients with chronic congestive heart failure (CHF) have impaired oxygen
      delivery to working muscles. The Dead Sea, the lowest site on earth, is
      distinguished by natural oxygen enrichment, low humidity, high barometric
      pressure, and temperature with increased bromide and magnesium concentrations in
      the inspired air. The aim of this study is to examine the effects of descent to
      the Dead Sea on patients with CHF. Twelve patients with CHF and 4 age-matched
      healthy controls underwent complete echocardiographic studies at rest as well as
      treadmill and metabolic stress tests, both in Haifa, 130 m above sea level and 3
      days after descent to the Dead Sea, 402 m below sea level. Significant changes in
      parameters at the Dead Sea compared with Haifa included time on treadmill, which
      increased from 612+/-198 to 672+/-1 86 seconds (p <0.05); the Borg scale
      decreased by 1 to 2 grades (p <0.05); and oxygen saturation increased by 3%
      throughout exercise (p <0.05). Systolic blood pressure decreased by 9 mm Hg at
      rest (p <0.05) and increased by 14 mm Hg at peak exercise at the Dead Sea in
      patients with CHF (p <0.05). Cardiac output at rest increased by 300 ml/min (p
      <0.05). Maximum oxygen consumption (VO2max) increased by 126 ml/ min (p <0.05),
      and even more so in patients with more severe exercise-induced oxygen
      desaturations, which was associated with lower peak minute ventilation to CO2
      production ratio (p <0.05). Thus, descent to the Dead Sea acutely improved
      exercise performance due to better oxygenation and loading conditions in patients
      with CHF.

PMID- 10072229
TI  - Effects of amiodarone on tumor necrosis factor-alpha levels in congestive heart
      failure secondary to ischemic or idiopathic dilated cardiomyopathy.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis
      of congestive heart failure and may be associated with an increase in mortality.
      A recent in vitro study showed that amiodarone decreases TNF-alpha production by
      human blood mononuclear cells in response to lipopolysaccharide. However, no
      previous clinical studies have determined the effect of chronic amiodarone
      therapy on TNF-alpha levels. Thus, the purpose of this study was to determine
      whether amiodarone affects TNF-alpha levels in patients with ischemic and
      nonischemic cardiomyopathy. TNF-alpha levels were analyzed by an enzyme-linked
      immunoassay using plasma samples at baseline, 1, and 2 years of follow-up in New
      York Heart Association class III patients (n = 40 in each of the placebo and
      amiodarone groups, mean ejection fraction 0.25+/-0.09) who were randomized in the
      Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy, a multicenter,
      double-blind, placebo-controlled study in which the effect of amiodarone on
      survival was investigated. TNF-alpha levels were elevated in both groups of
      patients at baseline, 6.6+/-3.1 and 7.7+/-5.3 pg/ml in the amiodarone and placebo
      groups, respectively (p = 0.3). There were no significant differences in
      demographic or clinical variables between the 2 groups. Amiodarone treatment was
      associated with a significant increase in TNF-alpha levels in patients with
      ischemic cardiomyopathy, 12.7+/-12.5 and 6.8+/-3.7 pg/ml in the amiodarone and
      placebo groups, respectively (p = 0.03) at 1 year. No change in TNF-alpha levels
      was observed in patients with nonischemic cardiomyopathy. In contrast to the in
      vitro data, amiodarone treatment is associated with an increase in TNF-alpha
      levels in patients with ischemic cardiomyopathy. This increase is not associated
      with an adverse effect on survival.

PMID- 10072230
TI  - Factors determining normalization of pulmonary vascular resistance following
      successful balloon mitral valvotomy.
AB  - Balloon mitral valvotomy (BMV) provides improvement in pulmonary vascular
      resistance (PVR) in patients with severe mitral stenosis. Its normalization,
      however, remains questionable. We evaluated PVR before, after BMV, and at follow
      up in 37 patients who had a previous successful BMV. Patients were divided into 2
      groups: group 1 had 21 patients with normalized PVR (<125 dynes/s/cm5) either
      after BMV or at follow-up, and group 2 had 16 patients with persistently abnormal
      PVR. Patients in group 2 were older than patients in group 1 (55+/-13 vs 43+/-14
      years, p = 0.01) and had atrial fibrillation more frequently (10 [63%] vs 6
      [29%], p = 0.04). Age, cardiac rhythm, mitral valve area, pulmonary bed gradient,
      pulmonary artery pressure, and PVR before the procedure were significant
      univariate predictors for normalization of PVR. Age, echocardiographic score,
      systolic pulmonary artery pressure, and mitral regurgitation were all independent
      determinants of normalization of PVR in a multivariate logistic regression model.
      We conclude that PVR failed to return to normal in 16 patients (43%) after
      successful BMV; this can be predicted by baseline clinical and hemodynamic
      parameters.

PMID- 10072231
TI  - Myocardial adenine nucleotides, glycogen, and Na, K-ATPase in patients with
      idiopathic dilated cardiomyopathy requiring mechanical circulatory support.
AB  - Acute decompensation leading to progressive pump failure is a main cause of death
      in patients with congestive heart failure. To find possible metabolic defects
      associated with the onset of this fatal occurrence, we measured myocardial
      adenine nucleotides, glycogen, and Na,K-ATPase in patients with end-stage
      idiopathic dilated cardiomyopathy. The biopsy specimens were obtained from the
      right ventricle of beating hearts during implantation of a biventricular
      assistance device in 23 patients (group I) suffering from irreversible
      cardiogenic shock and during heart transplantation in 20 patients (group II) in
      compensated heart failure. Left ventricular ejection fraction (LVEF) was
      determined preoperatively by echocardiography. Left ventricular function in group
      I was more severely impaired than in group II (LVEF 16.8%+/-4.6% vs 22.1%+/-5.1
      %; p <0.01). Myocardial adenosine triphosphate (ATP) in group I was significantly
      reduced in comparison with group II (119.4+/-10.2 vs 27.7+/-7.4 nmol/mg
      noncollagen protein; p <0.01). There was no difference in glycogen levels. Na,K
      ATPase concentration in group I (n = 8) was lower than that of group II (n = 20)
      (425+/-80 vs 498+/-75 pmol/g wet weight; p <0.05). Linear regression analyses
      showed a significant correlation between adenosine triphosphate (ATP) and LVEF (r
      = 0.41, p <0.01) and between Na,K-ATPase and LVEF (r = 0.55, p <0.01). These
      results indicate that loss of myocardial ATP and Na,K-ATPase could partially
      contribute to the development of spontaneous deterioration of the chronically
      overloaded heart.

PMID- 10072232
TI  - Immediate and follow-up findings after stent treatment for severe coarctation of
      aorta.
AB  - Experimental studies have shown that stents implanted at the aorta become
      incorporated within the aortic wall and can be further expanded in growing
      animals. Few clinical studies have shown that the stent repair of severe
      coarctation of aorta provides excellent initial results, and little is known on
      the follow-up of these patients. We assessed the immediate and follow-up results
      obtained in a series of 48 patients (mean age 14+/-12 years) with severe
      coarctation of the aorta who were treated by Palmaz stent implantation; 30 of
      them (63%) underwent angiographic follow-up studies at a mean of 25+/-11 months
      after treatment. Quantitative serial analysis of the aortogram (baseline, after
      treatment, and at follow-up) was performed. Significant relief (mean residual
      gradient 3+/-4 mm Hg) was always obtained after stent implantation. The isthmus,
      when hypoplastic (60%), was always expanded with the stent. One associated
      aneurysm became occluded after the implant. Complications included aortic
      disruption, stent migration, and decreased or absent femoral pulses. At
      angiographic follow-up, the stent remained always in place, without recoil. In 22
      patients (73%), there were no detectable neointimal proliferation at late
      angiogram; however, 8 patients (27%) had some degree of intimal thickening (1 to
      5 mm), causing mild restenosis in 3 patients treated at early age, and
      nonsignificant lumen reduction in 5. The serial aortogram analysis revealed a
      minor but significant increase in nonstented aortic diameters that seemed related
      to the normal growth of children. No need for stent reexpansion was observed at 2
      year follow-up (mean). Two patients (7%) developed late small aneurysm formation
      at the stented wall; both were occluded by the insertion of coils through the
      stent orifices. We conclude that stent treatment for severe coarctation of aorta
      provides excellent immediate and long-term results in young adults and children.
      However, at early age, restenosis by intimal growth may develop.

PMID- 10072233
TI  - Prognostic significance of clinically silent coronary artery fistulas.
AB  - Symptomatic coronary artery fistulas (CAF) are associated with significant
      morbidity and mortality. With the advent of high-resolution 2-dimensional and
      color Doppler echocardiography, the detection rate of clinically silent CAF has
      increased, but their clinical significance and outcome have not been defined. The
      clinical, echocardiographic, electrocardiographic, and angiographic findings and
      documented follow-up of 31 patients with an echocardiographic finding of a
      clinically silent coronary artery fistula from 1986 to 1997 were analyzed. Mean
      age at diagnosis was 7.2+/-8.4 years. Indications for echocardiography were
      murmur (n = 23), congenital heart disease (n = 2), cardiomegaly (n = 2), chest
      pain (n = 1), stridor (n = 1), syncope (n = 1), and chest trauma (n = 1). CAF
      were detected with color Doppler flow mapping in all patients. The origin of the
      fistula was from the left coronary artery system (n = 27), right coronary artery
      system (n = 3), and bilateral (n = 1). The exit sites were the pulmonary artery
      (n = 18), right ventricle (n = 8), right atrium (n = 2), and left ventricle (n =
      3). Global and regional left ventricular function were normal in all patients at
      presentation and follow-up. Spontaneous closure of the fistula was documented in
      7 patients (23%) at mean follow-up of 2.6+/-2.0 years. In 23 patients the fistula
      persisted without intervention. All patients remained asymptomatic, without
      adverse clinical events or evidence of ischemia at a mean age at follow-up of
      9.3+/-9.1 years (range 4 months to 42.0). Based on this experience, there is no
      evidence that clinically silent CAF diagnosed incidentally by color Doppler
      echocardiography are associated with adverse clinical outcome in childhood and
      adolescence. Conservative management with continued follow-up of these patients
      appears to be appropriate.

PMID- 10072234
TI  - Effect of dobutamine on regional left ventricular function measured by tagged
      magnetic resonance imaging in normal subjects.
AB  - The effect of inotropic stimulation on the pattern and magnitude of regional left
      ventricular contraction was studied using tagged magnetic resonance imaging to
      assess whether dobutamine exacerbates variation in regional contraction at rest.
      Dobutamine stress testing defines a normal response as a homogeneous increase in
      regional wall motion. In 8 normal subjects, 4 equally spaced left ventricular
      short-axis levels were imaged through systole using tagged magnetic resonance
      imaging. The baseline imaging sequence was repeated with 5-, 10-, 15-, and 20
      microg/kg/min dobutamine infusion. Regional myocardial displacement, radial
      thickening, and circumferential shortening were measured. The left ventricle was
      analyzed by level (base to apex) and wall (septum, inferior, lateral, anterior).
      Dobutamine did not alter baseline regional functional heterogeneity. Dobutamine
      infusion resulted in a uniform increase in displacement, radial thickening, and
      circumferential shortening from baseline to 10-microg/kg/min infusion without
      additional increases at higher doses.

PMID- 10072235
TI  - Burton Elias Sobel, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 10072236
TI  - Effect of acute testosterone on myocardial ischemia in men with coronary artery
      disease.
AB  - The effect of acute testosterone administration on exercise-induced myocardial
      ischemia was assessed in 14 men with coronary artery disease and low plasma
      testosterone concentrations in a study of randomized, double-blind, crossover
      design. Testosterone increased time to 1-mm ST-segment depression compared with
      placebo by 66 (15 to 117) seconds (p = 0.016), suggesting a beneficial effect of
      testosterone on myocardial ischemia in these patients.

PMID- 10072237
TI  - Protection from digoxin-induced coronary vasoconstriction in patients with
      coronary artery disease by calcium antagonists.
AB  - Intravenous digoxin induces constriction of normal and stenotic coronary arteries
      in patients with coronary artery disease, which may lead to ischemic
      complications. We found that pretreatment with oral nisoldipine and intracoronary
      nitroglycerin neutralizes this digoxin-induced effect.

PMID- 10072238
TI  - Impact of smoking on coronary atherosclerosis and remodeling as determined by
      intravascular ultrasonic imaging.
AB  - Using preintervention intravascular ultrasound among patients with coronary
      artery disease, the current study indicates that patients who smoked had a
      similar degree of reference and lesion site arterial area, plaque burden, lumen
      compromise, attenuated adaptive vascular remodeling response, and less lesion
      site calcification as nonsmokers.

PMID- 10072239
TI  - Predictors of outcome of medically treated patients with left main/three-vessel
      coronary artery disease by coronary angiography.
AB  - This study examined the prognostic value of single-photon emission computed
      tomography in angiographically high-risk patients with left main and/or 3-vessel
      coronary artery disease who were treated medically. Multivariable Cox survival
      analysis revealed the single-photon emission computed tomography score (based on
      size of perfusion abnormality, multivessel abnormality, left ventricular
      dilation, and lung uptake) as the only independent predictor of outcome.

PMID- 10072240
TI  - Circadian rhythm of acute pulmonary edema.
AB  - We found that the onset of acute pulmonary edema demonstrates circadian
      periodicity. Most episodes occur in the morning or at night. Pulmonary edema
      occurs more frequently during the colder months.

PMID- 10072241
TI  - Evaluation of outpatient initiation of antiarrhythmic drug therapy in patients
      reverting to sinus rhythm after an episode of atrial fibrillation.
AB  - The safety of a method of outpatient antiarrhythmic drug loading utilizing a
      continuous loop event recorder was evaluated. The findings suggest that the
      standard 2-day hospital admission for drug loading is not necessary in all
      patients and a method of outpatient loading may be equally safe.

PMID- 10072242
TI  - Warfarin safety and efficacy in patients with thoracic aortic plaque and atrial
      fibrillation. SPAF TEE Investigators. Stroke Prevention and Atrial Fibrillation.
      Transesophageal echocardiography.
AB  - Patients with atrial fibrillation and with documented aortic plaque who were
      assigned to adjusted-dose warfarin therapy (international normalized ratio 2.0 to
      3.0) had an annual rate of cholesterol embolization of 0.7% (95% confidence
      interval [CI] 0.1% to 5.3%/patient-year). Warfarin-assigned patients with plaque
      had a lower rate of embolic events (5.9%/year; 95% CI 3.0 to 12) than those on
      combination low-dose warfarin (international normalized ratio <1.5) plus aspirin
      (17.3%/year; 95% CI 11 to 27; p = 0.01).

PMID- 10072243
TI  - Retrograde fast pathway ablation for atrioventricular nodal reentry associated
      with markedly prolonged PR intervals.
AB  - Three patients with typical atrioventricular nodal reentrant tachycardia (AVNRT)
      and markedly prolonged PR intervals (>300 ms) without dual pathway physiology at
      baseline or during isoproterenol infusion underwent successful fast pathway
      ablation and remained asymptomatic without recurrent AVNRT, atrioventricular
      block, or symptomatic bradycardia for a mean of 19 months. In patients with
      recurrent AVNRT and markedly prolonged PR intervals, selective ablation of the
      retrograde fast pathway can eliminate AVNRT without further impairment of
      anterograde atrioventricular nodal function.

PMID- 10072244
TI  - Value of ST-segment depression during paroxysmal supraventricular tachycardia in
      the diagnosis of coronary artery disease.
AB  - We evaluated 39 patients >45 years old with paroxysmal supraventricular
      tachycardia (SVT), 21 of whom had ST-segment depression during SVT. Treadmill
      exercise testing, including thallium stress scintigraphy, was performed in all
      patients and coronary angiography in 21 patients with ST-segment depression.
      Based on the presence of abnormal findings on exercise electrocardiogram and/or
      thallium in 7 of 21 patients (33%) with ST-segment depression, with additional
      corroboration by angiographic data, we conclude that myocardial ischemia and
      coronary artery disease is one, but not the only, mechanism involved in the
      genesis of ST-segment depression during paroxysmal SVT.

PMID- 10072245
TI  - Does angiotensin-converting enzyme polymorphism influence the clinical
      manifestation and progression of heart failure in patients with dilated
      cardiomyopathy?
AB  - To evaluate the role of angiotensin-converting enzyme (ACE) polymorphism on the
      development of end-stage dilated cardiomyopathy, the ACE gene polymorphism of 90
      patients after heart transplantation because of this disease was compared with
      the population sample. No difference in gene frequencies was found, but when
      compared with the population sample there were fewer ID heterozygotes detected;
      no significant influence of ACE polymorphism on the course of the disease before
      transplantation was found.

PMID- 10072246
TI  - Follow-up after coil closure of patent ductus arteriosus.
AB  - A prospective serial follow-up after coil closure of patent ductus arteriosus in
      84 patients showed a cumulative duct closure up to 96% at the end of 2 years.
      Five patients underwent transient recanalization, and 4 patients required repeat
      procedure for residual shunt or recanalization.

PMID- 10072247
TI  - Relation of fibrinolytic potentiation by estrogen to coagulation pathway
      activation in postmenopausal women.
AB  - To determine whether enhanced fibrinolysis is a primary effect of estrogen or is
      secondary to activation of coagulation, we measured hemostatic factors before and
      after conjugated equine estrogen 0.625 mg/day for 1 month in 9 postmenopausal
      women. We found that potentiation of fibrinolysis is a primary effect of
      conjugated equine estrogens at this commonly used dosage in healthy
      postmenopausal women.

PMID- 10072248
TI  - Estrogen replacement therapy after coronary angioplasty.

PMID- 10072249
TI  - Relative risk reduction in trial results.

PMID- 10072250
TI  - Increased high-frequency power may not reflect increased vagal tone.

PMID- 10072251
TI  - Consensus recommendations for the management of chronic heart failure. On behalf
      of the membership of the advisory council to improve outcomes nationwide in heart
      failure.

PMID- 10072252
TI  - Lipoprotein (a): a controversial risk factor for atherosclerotic heart disease.

PMID- 10072253
TI  - Technology development in breath microanalysis for clinical diagnosis.
AB  - A new generation of breath tests detects trace amounts of endogenous volatile
      organic compounds (VOCs) present in the breath. The breath microanalysis is
      potentially fast and convenient. It opens up a new promising area of using the
      breath test as a noninvasive diagnostic tool for a variety of diseases. Recent
      developments in microanalysis technology are expected to greatly facilitate the
      use of the breath test in clinical evaluations and applications, and these
      developments are described in the present review.

PMID- 10072254
TI  - Cloning of the hereditary hemochromatosis gene: implications for pathogenesis,
      diagnosis, and screening.
AB  - Hereditary hemochromatosis (HH) is one of the most common genetic disorders
      affecting populations of European ancestry. It is characterized by an
      inappropriately high iron absorption that leads to iron overload preferentially
      in the parenchymal organs. Although the severity of the phenotype can be modified
      by a number of factors, it is clear that most homozygotes will eventually become
      symptomatic. Clinical manifestations are often nonspecific and easily overlooked.
      Untreated HH can be associated with substantial morbidity and mortality.
      Diagnosis in the pre-cirrhotic stage, however, results in normal life expectancy.
      Early diagnosis and the initiation of phlebotomy therapy are therefore keys to
      preventing complications related to iron overload. The recent isolation of a
      strong candidate gene for hemochromatosis has the potential to allow for genetic
      diagnosis and screening in the near future. This exciting finding is likely not
      only to change clinical practice but also to yield new insights into the poorly
      understood pathophysiology of the disease.

PMID- 10072255
TI  - Family history of early cardiovascular disease in children with moderate to
      severe hypercholesterolemia: relationship to lipoprotein (a) and low-density
      lipoprotein cholesterol levels.
AB  - Lipoprotein (a) (Lp(a)) is an established cardiovascular risk factor in adults.
      We sought to evaluate whether raised Lp(a) levels were predictive of a family
      history of early cardiovascular disease (CVD) in children already at increased
      risk for premature atherosclerosis because of elevated low-density lipoprotein
      (LDL) cholesterol levels. Lp(a) and serum lipid levels were measured in 69
      children and offspring with established moderate to severe hypercholesterolemia
      (serum cholesterol > 170 mg/dL) who were aged 10.7 +/- 4.3 years (range 1.5 to 21
      years) and had been referred to a pediatric lipid center. The children
      represented families with a positive (n = 27) or negative (n = 42) history for
      premature CVD (<55 years of age in parent or grandparent). In all children, Lp(a)
      levels ranged from 1 to 140 mg/dL, with a median of 29 mg/dL. Mean total
      cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol
      levels were 234 mg/dL, 166 mg/dL, and 45 mg/dL, respectively. There was no
      difference in median Lp(a) levels between the children with a positive family
      history and those with a negative family history (29.9 mg/dL vs 29.0 mg/dL,
      respectively). In contrast, children with a positive family history showed
      significantly higher LDL cholesterol levels (186 +/- 61 mg/dL vs 153 +/- 52
      mg/dL, P = .02). Thus, in this group of hypercholesterolemic children, LDL
      cholesterol but not Lp(a) levels were associated with a family history of
      premature CVD. Further studies are needed to identify additional specific risk
      factors associated with the development of CVD in this population.

PMID- 10072256
TI  - Influence of thrombin in suspension, surface activation, and high shear on
      platelet surface GPIb/IX distribution.
AB  - Studies in our laboratory have shown that glycoprotein Ib/IX (GPIb/IX), the
      receptor for von Willebrand factor (vWf), is not decreased in number or cleared
      from exposed surfaces to the internal membranes of platelets activated in
      suspension by thrombin alone, by interaction with formvar surfaces alone, or by a
      combination of the two modes of stimulation. The present study has examined the
      influence of three different types of stimulation including activation by
      thrombin in suspension followed by surface activation on formvar, then exposure
      to high shear stress in a flat chamber. Samples were fixed for study in the
      electron microscope after each single stimulus, after the combination of two
      modes of activation, and after the combination of suspension, surface, and shear
      activation and were stained by an immunogold procedure using monoclonal
      antibodies to localize GPIb/IX on singly, doubly, or multiply activated cells.
      The results demonstrate that GPIb/IX receptors remain on activated platelets from
      edge to edge and that there is no difference in the number or distribution of
      receptor complexes on thrombin-activated platelets, surface-activated cells, or
      platelets exposed to the combination of suspension, surface, and shear
      activation. The findings add additional support to the concept that GPIb/IX is
      not a mobile receptor and is not cleared from exposed surfaces to internal
      membranes under physiologic conditions.

PMID- 10072257
TI  - Alterations in body weight, breaking strength, and wound healing in Wistar rats
      treated pre- and postoperatively with erythropoietin or granulocyte macrophage
      colony stimulating factor: evidence of a previously unknown anabolic effect of
      erythropoietin?
AB  - Several growth factors, such as growth hormone and insulin-like growth factor-1,
      have been used to reverse the high rate of catabolism observed either after an
      operation or during serious illness. We conducted a pilot study in Wistar rats in
      an attempt to assess whether regulatory peptides widely used in clinical
      practice, such as erythropoietin (EPO) and granulocyte macrophage colony
      stimulating factor (GM-CSF), alone or in combination, might influence the
      metabolism after surgery. Forty animals were randomly allocated into four groups
      (one control group and three experimental groups; 10 animals per group). The rats
      in the control group received isotonic NaCl; the rats in one experimental group
      received recombinant human EPO (rHuEPO) at a dose of 500 IU/kg (EPO group) and
      those in another received recombinant GM-CSF at a dose of 20 microg/kg (GM-CSF
      group); in the fourth group, each animal received the two drugs in combination
      (EPO/GM-CSF group). In all groups, rats were given the drug(s) or NaCl daily for
      15 days before the operation and for 7 days after the operation until they were
      killed. We estimated the body weight (g) and the hematocrit (%) on the first day
      of the experiment (baseline values) and on the seventh day after the operation,
      and we estimated the rate of healing and the breaking strength of the intestinal
      anastomosis on the day the rats were killed. At the end of the study we found
      that the body weight (median 250 g, minimum 230 g, maximum 270 g) and the levels
      of hematocrit (median 64%, minimum 60%, maximum 65%) were significantly increased
      in the EPO group (P < .001 and P < .005, respectively) as compared with the
      baseline values (median 217.5 g, minimum 200 g, maximum 250 g; median 51.5%,
      minimum 45%, maximum 55%, respectively). A similar significant increase in body
      weight (median 230 g; minimum 200 g; maximum 250 g) and hematocrit (median 64%;
      minimum 59%; maximum 67%) was found at the end of the study in the EPO/GM-CSF
      group (P = .01 and P < .005, respectively) as compared with the baseline values
      (median 210 g; minimum 200 g; maximum 250 g; median 50%, minimum 48%, maximum
      54%, respectively). The breaking strength (in newtons (N)) statistically differed
      in the four groups (Kruskal-Wallis, P = .0008). A comparison between groups
      showed that the breaking strength had been significantly increased in the animals
      in the EPO group (median 2.18 N, minimum 1.98 N, maximum 2.44 N) as compared with
      those in the control group (median 1.66 N, minimum 1.33 N, maximum 1.87 N; P =
      .004), GM-CSF group (median 1.73 N, minimum 1.25 N, maximum 2.07 N; P < .005),
      and EPO/GM-CSF group (median 1.71 N, minimum 1.37 N, maximum 1.91 N; P = .0005).
      In conclusion, this study demonstrated that the administration of rHuEPO appears
      to have a beneficial positive effect on the body weight, hematocrit, and healing
      rate and the breaking strength of large bowel anastomoses in rats. These
      observations provide evidence of an as-yet-unknown anabolic effect of EPO, and
      they may expand its usual applications. However, more studies are needed to
      confirm our findings and furthermore to define the optimal dose and timing of EPO
      administration.

PMID- 10072258
TI  - Spontaneous inhibitors of factor VIII: kinetics of inactivation of human and
      porcine factor VIII.
AB  - Autoantibodies to factor VIII (FVIII)(spontaneous inhibitors) often inactivate
      FVIII in a complex fashion (type II inhibitors) as compared with alloantibodies
      (hemophilic inhibitors), which usually demonstrate second-order reaction kinetics
      (type I inhibitors). The infusion of porcine FVIII in patients with spontaneous
      inhibitors may give rise to anti-porcine FVIII antibodies. The purpose of this
      study was to determine whether these were type I or type II inhibitors. Plasma
      from 8 patients with spontaneous inhibitors and 6 patients with hemophilia with
      inhibitors were studied. Equal volumes of patient plasma and either pooled normal
      human plasma or porcine FVIII (Hyate-C) were incubated at 37 degrees C for 90
      minutes. Aliquots were removed immediately after mixing and at 30-minute
      intervals and assayed for FVIII by using a two-stage method. The values for
      residual FVIII were log-transformed and plotted against the time of incubation,
      and the resultant curves were analyzed for goodness of fit (coefficient of
      determination, r2) by using linear and exponential equations. The values were
      examined by paired t tests; P values were two-tailed. Values are expressed as
      mean +/- SD. The titers of spontaneous inhibitors against human FVIII ranged from
      2.6 to 416 Bethesda Units (BU), and those against porcine FVIII ranged from 0.7
      to 47 BU. Samples were diluted so that the FVIII levels in the mixtures before
      incubation were similar: human, 0.44 U/ml; porcine, 0.47 U/ml; P = not
      significant. Four of the 8 patients with spontaneous inhibitors inactivated human
      FVIII in a fashion consistent with complex kinetics; their r2 values with the
      linear equation were less than 0.90. All r2 values improved when the exponential
      equation was used (linear, 0.90 +/- 0.08; exponential, 0.92 +/- 0.06; P = .007).
      In contrast, r2 values with porcine FVIII were the same (0.94) with either the
      linear or the exponential equation (P = not significant). r2 for the 6 hemophilic
      inhibitors showed no significant difference between the linear and exponential
      equations; the values were 0.99 with human FVIII and 0.95 with porcine FVIII. In
      non-hemophilic patients, antibodies developing to porcine FVIII have kinetics of
      inhibition that are second order (type I), even though antibodies to human FVIII
      in these same patients may have complex (type II) kinetics.

PMID- 10072259
TI  - Tumor necrosis factor-alpha stimulates attachment of small cell lung carcinoma to
      endothelial cells.
AB  - Tumor cell attachment to endothelial cells (ECs) is an important step in the
      metastasis of small cell lung carcinoma (SCLC). Tumor necrosis factor-alpha (TNF
      alpha) stimulation of ECs increases the attachment of some malignant cell types
      to ECs by affecting the expression of cell adhesion molecules (CAMs). Similarly,
      the inhibition of EC protein kinase C (PKC) and tyrosine kinase (TK) pathways
      modulates TNF-alpha-mediated effects on CAM expression. We hypothesized that TNF
      alpha would increase SCLC attachment to ECs by affecting CAM expression through
      activation of PKC and TK pathways. To test this hypothesis, human umbilical vein
      endothelial cells (HUVECs) were stimulated with TNF-alpha (0 to 500 U/mL) for
      variable time periods (1 to 24 hours), and the attachment of H82 cells (an SCLC
      cell line) to the HUVECs was quantified. TNF-alpha stimulation of the HUVECs
      increased H82 attachment from 28.1% +/- 1.6% to 48.8% +/- 1.7% (P < .05).
      Preincubation of HUVECs with the PKC inhibitors bis-indolylmaleimide (BIN) or
      calphostin C or the TK inhibitors genistein or herbimycin A (HMA) blocked the TNF
      alpha-induced increase in H82 cell attachment. The addition of antibodies to
      vitronectin (Vn) or beta1-integrin to TNF-alpha-activated HUVECs before the
      addition of the H82 cells also significantly decreased H82 attachment, whereas
      the addition of antibodies to E-selectin, P-selectin, vascular cell adhesion
      molecule (VCAM), intercellular adhesion molecule (ICAM), neural cell adhesion
      molecule (NCAM), sialyl-Lewis(x), fibronectin (Fn), alpha(v)-integrin, alpha3
      integrin, alpha4-integrin, or alpha5-integrin had no effect on SCLC attachment.
      In summary, the TNF-alpha-mediated increase in SCLC attachment to ECs appears to
      be mediated by the activation of EC PKC and TK pathways as well as through
      effects on the function or expression of EC Vn and beta1 integrin.

PMID- 10072260
TI  - Urokinase is required for T lymphocyte proliferation and activation in vitro.
AB  - We have previously demonstrated that urokinase-deficient (uPA-/-) mice do not
      increase lung T lymphocyte number and fail to mount protective immune responses
      during pulmonary Cryptococcus neoformans infection. These observations suggest a
      previously unconsidered role for urokinase-type plasminogen activator (uPA) in T
      lymphocyte-mediated immune responses. Accordingly, we sought to determine whether
      uPA is required for T cell receptor-mediated (TCR-mediated) lymphocyte
      proliferation and activation. Splenocytes from uPA-/- and uPA+/+ mice were
      stimulated with concanavalin A (Con A). The uPA-/- mice had diminished T cell
      proliferation as compared with uPA+/+ mice. Coculturing uPA-/- T cells with
      uPA+/+ accessory cells led to the restoration of proliferation. Similarly, T cell
      proliferation induced by CD3 cross-linking was diminished in uPA-/- mice as
      compared with uPA+/+ mice. T lymphocyte activation, defined as the induced
      expression of antigens and the elaboration of cytokines, was determined. The
      expression of CD69 and that of CD49d were diminished in response to Con A
      stimulation in uPA-/- mice as compared with uPA+/+ mice. The elaboration of
      cytokines in response to Con A was also altered in the uPA-/- mice. The
      production of the Th1 cytokines interferon-gamma and interleukin-12 was
      diminished in uPA-/- mice as compared with uPA+/+ mice. The uPA-/- mice produced
      increased amounts of interleukin-10, a Th2 cytokine. We conclude that the lack of
      uPA results in impaired T cell activation and proliferation in response to TCR
      mediated signaling and the expression of a less Th1-polarized profile of
      cytokines. These findings suggest that the inability of uPA-/- mice to combat
      Cryptococcus neoformans infection may be caused by the impairment of T lymphocyte
      immune responses in the absence of uPA.

PMID- 10072261
TI  - Ureteral obstruction reverses glomerular proliferation in immune complex
      glomerulonephritis.
AB  - We investigated an effect of ureteral obstruction on a progressive immune complex
      glomerulonephritis in murine lupus erythematosus. Unilateral ureteral obstruction
      for 8 days significantly decreased the expanded glomerular mesangial area, as
      measured by computer-assisted morphometry (4.44 +/- 0.33 x 10(-4) mm2 to 3.60 +/-
      0.34 x 10(-4) mm2, P < .05), and reduced the staining for IgG, C3, and
      extracellular matrix components, whereas the nephritis was exacerbated in the
      contralateral non-obstructed kidney. The renal concentration of prostaglandin E2
      (PGE2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in the obstructed
      kidneys 8 days after obstruction significantly exceeded that of kidneys in sham
      operated controls (344.2 +/- 83.9 pg/mg tissue protein vs 50.0 +/- 27.5 pg/mg
      tissue protein, P < .01; 71.9 +/- 11.4 pg/mg tissue protein vs 9.5 +/- 2.3 pg/mg
      tissue protein, P < .01), whereas thromboxane B2 (TxB2) levels were similar in
      the two groups (33.9 +/- 4.5 pg/mg tissue protein vs 31.3 +/- 2.6 pg/mg tissue
      protein). Next, an experiment was performed to evaluate the role of renal
      eicosanoids in the amelioration in the immune complex glomerulonephritis after
      ureteral obstruction. Treatment with the cyclooxygenase inhibitor indomethacin
      abolished the decrease in mesangial area induced by ureteral obstruction (7.7% +/
      6.9%). CV-4151, a thromboxane synthetase inhibitor, had no effect on the
      decrease in mesangial area (-25.8% +/- 6.8%, P < .05). We conclude that
      unilateral ureteral obstruction quickly decreased the mesangial expansion in
      immune complex glomerulonephritis, and vasodilatory eicosanoids such as PGE2 and
      PGI2 at least partly contribute to the amelioration of glomerular histology.

PMID- 10072262
TI  - Carbamylated proteins activate glomerular mesangial cells and stimulate collagen
      deposition.
AB  - Carbamylated proteins formed in renal insufficiency from the spontaneous
      decomposition of urea exert a variety of metabolic effects. Here we examined the
      effects of carbamylated proteins on glomerular mesangial cells to determine
      whether urea retention in early renal insufficiency may itself promote glomerular
      sclerosis and hasten the progression to kidney failure. To this effect we
      carbamylated fetal bovine serum proteins in vitro and tested their effect on
      mesangial cell proliferation (by tritiated thymidine uptake), de novo protein
      synthesis (by tritiated leucine uptake), collagen I and collagen IV accumulation
      (by avidin-biotin enzyme immunoassay), and gelatinase levels in the medium (by
      zymography and quantitative fluorescence assay). Carbamylated fetal bovine serum
      at concentrations present in uremia increased tritiated thymidine incorporation
      by 50% without altering tritiated leucine incorporation, and it increased
      collagens I and IV in the monolayer by 150% to 300%. Gelatinase activity was
      unchanged. We conclude that carbamylated proteins can activate mesangial cells to
      a profibrogenic phenotype. From a clinical perspective, the carbamylation of
      proteins by elevated urea levels may accelerate the progression to kidney failure
      and thus set up a vicious cycle in which the nitrogen retention itself would
      cause further progression of fibrosis and deterioration of kidney function.

PMID- 10072263
TI  - Elevated concentrations of plasma alpha-melanocyte stimulating hormone are
      associated with reduced disease progression in HIV-infected patients.
AB  - To determine whether concentrations of the anti-inflammatory peptide alpha
      melanocyte stimulating hormone (alpha-MSH) are associated with accelerated or
      reduced disease progression in patients with HIV infection, plasma concentrations
      of alpha-MSH and two other anticytokine molecules, interleukin-1 receptor
      antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were
      taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87
      patients were collected by using special precautions to ensure accurate
      measurement of the peptide. Alpha-MSH concentrations were determined by
      radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using
      enzyme-linked immunosorbent assays. Clinical and immunologic variables were
      recorded to determine whether there is an association between cytokine antagonist
      concentrations and disease progression. Elevated concentrations of circulating
      alpha-MSH were associated with reduced progression of the disease. Circulating
      alpha-MSH was greater in non-progressors than in progressors; the association
      between elevated alpha-MSH and reduced disease progression was even more
      pronounced in patients with baseline CD4+ T cell counts less than 200/microL. No
      such association was observed for the other two anticytokine molecules, and there
      was no significant correlation between the plasma concentration of either
      cytokine antagonist and alpha-MSH. The present evidence and previous findings
      indicate that elevated concentrations of alpha-MSH are associated with reduced
      disease progression in HIV-infected patients.

PMID- 10072264
TI  - Impact of gowning on visit length.

PMID- 10072265
TI  - Needs assessment following hurricane Georges--Dominican Republic, 1998.
AB  - Hurricane Georges struck the Carribean Islands in September 1998, causing
      numerous deaths and extensive damage throughout the region. The Dominican
      Republic was hardest hit, with approximately 300 deaths; extensive infrastructure
      damage; and severe agricultural losses, including staple crops of rice, plantain,
      and cassava. Two months after the hurricane, the American Red Cross (ARC) was
      asked to provide food to an estimated 170,000 families affected by the storm
      throughout the country. To assist in directing relief efforts, CDC performed a
      needs assessment to estimate the food and water availability, sanitation, and
      medical needs of the hurricane-affected population. This report summarizes the
      results of that assessment, which indicate that, 2 months after the disaster, 40%
      of selected families had insufficient food > or =5 days per and 28% of families
      reported someone in need of medical attention.

PMID- 10072266
TI  - Human rabies--Virginia, 1998.
AB  - On December 31, 1998, a 29-year-old man in Richmond, Virginia, died from rabies
      encephalitis caused by a rabies virus variant associated with insectivorous bats.
      This report summarizes the clinical and epidemiologic investigations by the
      Virginia Department of Health and CDC.

PMID- 10072267
TI  - Blastomycosis acquired occupationally during prairie dog relocation--Colorado,
      1998.
AB  - On August 31, 1998, two suspected cases of fungal pneumonia were reported to the
      Boulder County (Colorado) Health Department (BCHD). Both patients were
      immunocompetent, otherwise healthy adults working for the City of Boulder Open
      Space (CBOS) program on a prairie dog relocation project. This report summarizes
      the epidemiologic investigation by BCHD, the Colorado Department of Public Health
      and Environment, and CDC; the findings indicate that these two persons acquired
      blastomycosis in Colorado, which is outside the area where the disease is
      endemic.

PMID- 10072268
TI  - Insurance coverage of unintended pregnancies resulting in live-born infants-
      Florida, Georgia, Oklahoma, and South Carolina, 1996.
AB  - In the United States during 1994, approximately 49% of all pregnancies, excluding
      miscarriages, were unintended. Unintended pregnancy can result in adverse health
      outcomes that affect the mother, infant, and family. Little is known about the
      distribution of unintended pregnancy with respect to the payment source for
      health care. In the absence of data for periconceptional payment source for
      health care, prenatal-care payment source is used as a surrogate. To develop
      recommendations to reduce unintended pregnancy, CDC analyzed insurance coverage
      specific prevalences of live-born infants from unintended pregnancies among women
      aged 20-34 years using data from the Pregnancy Risk Assessment and Monitoring
      System (PRAMS) for 1996 (the most recent year for which data are available). This
      report summarizes the results of this analysis, which indicates that the highest
      rates of unintended pregnancy occurred among women covered by Medicaid, with
      lower rates among women covered by health-maintenance organizations (HMOs) or
      private insurance.

PMID- 10072269
TI  - Surfactant Scavenging and Surface Deposition by Rising Bubbles.
AB  - When bubbles rise through a liquid they are known to scavenge dissolved surface
      active materials (surfactants). Small bubbles in the size range of tens of
      micrometers quickly become covered with surfactants in any but the cleanest
      conditions. This has the effect of immobilizing the bubble surface and affecting
      the drag and therefore the bubble rise speed. A large number of bubbles rising as
      a cloud toward a free surface will populate the bulk surface with surfactants at
      a richness that far exceeds that which would occur in the absence of bubbling.
      However, in addition to the increased deposition of surfactants on the bulk
      surface, the random and agitated motions of the rising bubbles induce mixing of
      the liquid. In a companion paper (R. L. Stefan and A. J. Szeri, submitted for
      publication) the mixing properties of a bubble cloud rising toward a free surface
      were determined. In the present work, a model for the uptake of surfactants by
      bubbles and subsequent deposition on the bulk surface is developed including the
      crucial feature of bubble-induced fluid mixing. It is found that the mixing of
      desorbed surfactant down into the bulk is key to predicting what will be the
      enrichment of the bulk surface. Copyright 1999 Academic Press.

PMID- 10072270
TI  - Interactions between Silica Colloids with Magnetite Cores: Diffusion,
      Sedimentation and Light Scattering.
AB  - The magnetic and Van der Waals attraction between uncharged silica spheres with a
      magnetic core has been studied using sedimentation and static and dynamic light
      scattering techniques. Specifically the effect of the interactions on the
      concentration dependence of the sedimentation velocity, diffusion, and the
      apparent radius of gyration was investigated. It was found experimentally that
      the concentration dependence is decreased significantly as a result of the Van
      der Waals and magnetic attractions and even may change sign in comparison to the
      hard-sphere case. Calculations of the (linear) concentration dependence for weak
      interactions predict this decrease and also indicate that for the silica
      magnetite particles the second virial coefficient passes a maximum with
      increasing silica layer thickness. Copyright 1999 Academic Press.

PMID- 10072271
TI  - Morphological Characterization of the Molecular Superstructure of Polyphenylene
      Ethynylene Derivatives.
AB  - Two different polyphenylene ethynylene derivatives, one partly hydrophobic and
      one hydrophilic, were investigated with a combination of X-ray and light
      scattering techniques and hydrodynamic techniques, as well as scanning force
      microscopy and transmission electron microscopy to elucidate their molecular
      structure and aggregation behavior in tetrahydrofuran and water, respectively. It
      turns out that both polymers possess a rod-like molecular architecture which,
      however, is the basis of a cascade of aggregation steps. Both, electron
      microscopy and X-ray analysis support the concept of a primary back-to-back
      aggregation of polymer chains into cylindrically shaped aggregates with high
      anisometry. The thickness of these aggregates was between 4.0 and 4.5 nm. The
      aggregates of the hydrophobic polymer further associate into fibrils and these
      fibrils form clusters of globular shape, though with high internal anisometry.
      Copyright 1999 Academic Press.

PMID- 10072272
TI  - Partition Coefficients and Interfacial Activity for Polar Components in Oil/Water
      Model Systems.
AB  - Partition coefficients, surface tension, and interfacial tension for some polar
      organic components dissolved in oil/water model systems have been investigated.
      The systems consist of isooctane modeling the oil phase and of water solutions of
      NaCl and CaCl2 modeling the water phase. The organic compounds examined were 1
      naphtoic acid, 5-indanol, and quinoline, all well-defined molecules known to be
      representative of polar components in crude oil. The dependence on pH, salinity,
      and ionic strength in the water phase was investigated. The surface tension and
      interfacial tension were also examined as a function of component concentration.
      The results show a connection between the distribution of the polar components
      and the interfacial tension. Correspondence between the partition coefficient and
      the pKa value for the components is also reported. For 1-naphtoic acid none of
      the two ionization forms of the molecule are found to be surface active in
      aqueous solution. For 5-indanol both forms are surface active, and for quinoline
      only the nonionic form of the molecule is found to be surface active. The results
      indicate that the aqueous phase is the one that governs the interfacial tension.
      Increasing salinity increases the concentration of the component in the oil phase
      and decreases the interfacial tension between the oil phase and the aqueous
      phase. The results are explained due to the "salting-out" effect and to changes
      in the electrostatics for the various systems. Copyright 1999 Academic Press.

PMID- 10072273
TI  - Computational Studies on Interaction between Air Bubbles and Hydrophobic Mineral
      Particles Covered by Nonpolar Oil.
AB  - Computations based on the extended DLVO theory are carried out on the potential
      energies of interactions between air bubbles and talc particles covered by
      nonpolar oil. It is shown that the major role of nonpolar oil in this system is
      to greatly increase the depth of the primary energy valley, giving rise to a much
      stronger bubble-particle aggregate that can support greater aggregate-rupture
      force fields from turbulent flows. Also, due to nonpolar oil involvement, the
      energy barrier between bubbles and mineral particles sharply collapses down and
      further separates, indicative of a greater probability of attachment of mineral
      particles to air bubbles. A linear relationship is found between the primary
      energy valley and the contact angles of oil or bubbles, and thus a simple and
      approximate formula is presented to evaluate the depth of the primary energy
      valley. In addition, it is found that the primary energy valley and the energy
      barrier are directly proportional to the effective particle radius, but the
      barrier location is independent of the effective particle radius. Copyright 1999
      Academic Press.

PMID- 10072274
TI  - Physical and Chemical Properties of Magnetite and Magnetite-Polymer Nanoparticles
      and Their Colloidal Dispersions.
AB  - The properties of polymer-coated magnetite nanoparticles, which have the
      potential to be used as effective magnetic resonance contrast agents, have been
      studied. The magnetite particles were synthesized by using continuous synthesis
      in an aqueous solution. The polymer-coated magnetite nanoparticles were
      synthesized by seed precipitation polymerization of methacrylic acid and
      hydroxyethyl methacrylate in the presence of the magnetite nanoparticles. The
      particle size was measured by laser light scattering. It was shown that the
      particle size, variance, magnetic properties, and stability of aqueous magnetite
      colloidal dispersion strictly depend on the nature of the stabilizing agent. The
      average hydrodynamic radius of the magnetite particles was found to be 5.7 nm in
      the stable aqueous colloidal dispersion. An inclusion of the magnetite particle
      into a hydrophilic polymeric shell increases the stability of the dispersion and
      decreases the influence of the stabilizing agent on the magnetic and structural
      properties of the magnetite particles as was shown by X-ray diffraction and
      Mossbauer and IR spectroscopy, as well as by vibrating sample magnetometry. The
      variation in the polymeric shell size and the polymer net density can be useful
      tools for evaluation of the polymer-coated magnetite particles as effective
      contrast agents. Copyright 1999 Academic Press.

PMID- 10072275
TI  - Temperature-Responsiveness of A-B-A Block Telomers at Solid-Liquid Interfaces.
AB  - Macroinitiators were prepared by coupling disuccinimidyl ester of 4,4'
      azobis(cyanovaleric acid) with poly(N-isopropylacrylamide) (PIPA), which had an
      amino group at its end. Styrene was telomerized with the initiators in THF. When
      the styrene content in the A-B-A block telomer obtained (PIPA-b-PSt-b-PIPA) was
      high, the telomer formed an irreversible aggregation resulting in microspheres,
      whereas the telomer with a much shorter styrene block could be dispersed
      monomolecularly. The telomers dispersed in water were aggregated by raising the
      temperature above 32 degrees C due to a coil-globule transition of PIPA moieties.
      The PIPA-b-PSt-b-PIPA could be strongly adsorbed to polystyrene (PSt) solid
      surfaces to form a layer, and the PSt blocks might lay on the PSt surface and the
      PIPA blocks might direct to the solution phase. The contact angle of air bubbles
      on the surface of telomer-coated PSt in the air-in-water system was dependent on
      temperature; that is, with the increase in temperature the contact angle of air
      bubbles largely decreased and leveled off above the coil-globule transition
      temperature (Tc). Correspondingly, the amount of protein Concanavalin A adsorbed
      to the telomer layer deposited on the PSt surface increased gradually with an
      increase in temperature and leveled off above the Tc. These phenomena were
      attributed to the changes in hydrophobicity of the telomer layer below and above
      the Tc. The usefulness of macroinitiators in preparing various kinds of block
      telomers which have responsiveness to external stimuli was strongly suggested.
      Copyright 1999 Academic Press.

PMID- 10072276
TI  - Electroosmotic Transport through a Cation-Exchange Membrane: Effect of the
      Stirring on the Dependence of the Electroosmotic Permeability on the Temperature.
AB  - The electroosmotic flux through a cation-exchange membrane has been obtained in
      different situations. From these measurements, the apparent electroosmotic
      permeability, W, of a cation-exchange membrane has been determined as a function
      of the temperature, T, and the stirring rate, v, of the solutions. In all the
      experimental situations studied, W decreases when v increases, while it can
      increase or decrease with T depending on the temperature range considered. For
      this last reason, the (T,W) curves show a minimum whose value and position depend
      on the experimental conditions established. The influence of the concentration
      polarization effect in the value of W and in its dependence with v and T is
      studied and quantified. Copyright 1999 Academic Press.

PMID- 10072277
TI  - Chemically Modified Human Immunoglobulin G: Hydrophobicity and Surface Activity
      at Air/Solution Interface.
AB  - Covalent modification of human IgG by fatty acid esters (C8 and C16) of N
      hydroxysuccinimide was carried out. Surface hydrophobicity measurements, using
      the fluorescent probe 8-anilino-1-naphthalenesulfonate, indicate an increase in
      the surface protein hydrophobicity with an increase in the number and in the
      length of the attached alkyl chains. The modified IgGs decrease surface tension
      at the air/solution interface more effectively than the native protein. The
      values of the molecular cross-sectional areas (DeltaA) estimated from the kinetic
      data are in the range of 100-300 A2 and reflect the size of protein segments at
      the interface during the adsorption process. About 40-50% increase in the DeltaA
      was observed upon attachment of the C8 groups to the native IgG. The lengthening
      of the bound alkyl chain from C8 to C16 results in a further increase in this
      value. The influence of the overall IgG hydrophobicity and the length of the
      attached alkyl chain on the dimensions of the mobile protein segment at the
      surface are discussed. Copyright 1999 Academic Press.

PMID- 10072278
TI  - Concentration Polarization of Interacting Solute Particles in Cross-Flow Membrane
      Filtration.
AB  - A theoretical approach for predicting the influence of interparticle interactions
      on concentration polarization and the ensuing permeate flux decline during cross
      flow membrane filtration of charged solute particles is presented. The Ornstein
      Zernike integral equation is solved using appropriate closures corresponding to
      hard-spherical and long-range solute-solute interactions to predict the radial
      distribution function of the solute particles in a concentrated solution
      (dispersion). Two properties of the solution, namely the osmotic pressure and the
      diffusion coefficient, are determined on the basis of the radial distribution
      function at different solute concentrations. Incorporation of the concentration
      dependence of these two properties in the concentration polarization model
      comprising the convective-diffusion equation and the osmotic-pressure governed
      permeate flux equation leads to the coupled prediction of the solute
      concentration profile and the local permeate flux. The approach leads to a direct
      quantitative incorporation of solute-solute interactions in the framework of a
      standard theory of concentration polarization. The developed model is used to
      study the effects of ionic strength and electrostatic potential on the variations
      of solute diffusivity and osmotic pressure. Finally, the combined influence of
      these two properties on the permeate flux decline behavior during cross-flow
      membrane filtration of charged solute particles is predicted. Copyright 1999
      Academic Press.

PMID- 10072279
TI  - A Direct Method of Studying Polymer Adsorption onto Mica Surfaces Using a
      Commercial Mettler Ultramicrobalance.
AB  - This paper deals with a simple and direct method of determining absolute values
      of adsorbance, i.e., mass per unit area, of polymers adsorbed from solution onto
      mica surfaces. The method is based on direct weighing of mica sheets using a
      Mettler ultramicrobalance UMT2 or UM3 (readability 1 x 10(-4) mg), which is
      commercially available. A set of mica sheets is weighed twice: before and after
      the immersion of mica sheets in polymer solution for a given period of time. The
      difference in weight of the mica sheets gives the mass of adsorbed polymers,
      which is divided by the total area of mica surface to derive the adsorbance.
      Measurable change in adsorbance was 0.1 mg m-2 in consideration of the size of
      mica sheets (50 cm2 in total surface area) and the scatter of readings of the
      ultramicrobalance. A detailed description is given on the apparatus and
      procedures for weighing and adsorption experiments. The present method has been
      applied to the experiments on the adsorption kinetics of polystyrene from
      cyclohexane and of bovine serum albumin from aqueous solution onto mica surfaces.
      Some of the experimental results are presented to show the practical examples of
      the application of this method. Copyright 1999 Academic Press.

PMID- 10072280
TI  - Dynamics of Growth and Breakup of Viscous Pendant Drops into Air.
AB  - This paper presents a numerical study of the dynamics of a viscous liquid drop
      that is being formed directly at the tip of a vertical tube into ambient air. A
      model is developed to predict the evolution of the drop shape and its breakup
      based on RIPPLE, which is a solution algorithm for computing transient, two
      dimensional, incompressible fluid flow with surface tension on free surfaces of
      general topology (D. B. Kothe and R. C. Mjolsness, AIAA J. 30, 2694 (1992)). The
      full Navier-Stokes system is solved by using finite-difference formulation on a
      Eulerian mesh. The mesh is fixed in space, with the flow and surface moving
      through it to ensure accurate calculations of complex free surface flows and
      topology, including surface breakup and coalescence. The novel feature of the
      numerical algorithm is the use of a Eulerian volume-tracking approach which
      allows the calculations to pass the breaking point during formation of a drop
      continuously without interruption or numerical modification and, therefore, to
      explore the features of generation of satellite droplets. The effects of physical
      and geometric parameters on the nonlinear dynamics of drop growth and breakup are
      investigated. The focus here is on drop breakup and subsequent formation of
      satellite droplets. The effects of finite inertial, capillary, viscous, and
      gravitational forces are all accounted for to classify different formation
      dynamics and to elucidate features of satellite droplet generation. The numerical
      predictions are compared with experimental measurements for water drops, and the
      results show good agreement. Copyright 1999 Academic Press.

PMID- 10072281
TI  - Effects of Adsorbed Polyaniline on Redox Process on MoO3 Surface.
AB  - The effects exhibited by adsorbed conducting polyaniline on the redox process on
      a molybdenum oxide surface were studied. Thermogravimetric results indicate a 4%
      polyaniline deposition. Cyclic voltammograms of the adsorbed polymer on MoO3 show
      that polyaniline exerts remarkable effects on the molybdenum blue oxidation
      reduction process, with oxidation and reduction potentials of 0.33 and 0.18 V,
      respectively. This effect strongly enhances the electrode response, and can be
      used as an important tool in qualitative and/or quantitative determinations of
      molybdenum in solution as well as in any substrate. Copyright 1999 Academic
      Press.

PMID- 10072282
TI  - Approximate Expression for the Double-Layer Interaction Energy between Two
      Parallel Plates with Constant Surface Charge Density.
AB  - An approximate expression for the potential energy of the double-layer
      interaction between two parallel similar plates with constant surface charge
      density is derived via a novel linearization method, in which the Poisson
      Boltzmann is linearized with respect to the deviation of the electric potential
      from the surface potential (which is a function of the interplate separation h).
      This approximation works quite well for small plate separations h for all values
      of the surface charge density (or the unperturbed surface potential) and gives a
      correct limiting form of the interaction energy (or the interaction force) as h -
      > 0. Copyright 1999 Academic Press.

PMID- 10072283
TI  - Hydrodynamic Surface Flow and the Swelling Effect of C2 and C4 Alkenes through
      Anhydrous Ag+-Doped Perfluorocarbon Type Ion-Exchange Membranes.
AB  - The transport mechanism was investigated for n-butane, 1-butene, ethane, and
      ethene through anhydrous Ag+-doped PSM at various upstream gas pressures. 1
      Butene and ethene molecules can be adsorbed and form multilayers on the Ag+ sites
      in the membrane. Their adsorption behavior can be described by the BET n-layer
      adsorption theory. These adsorbed alkene molecules can also swell the surrounding
      polymer chains to a certain extent, causing resistance to the migration of these
      alkene multilayer molecules to decrease as the concentration of the adsorbed
      alkenes increases. The permeation behavior of 1-butene and ethene is mainly
      controlled by the hydrodynamic surface flow mechanism, and their fluxes are much
      higher than those of alkanes, especially at high upstream gas pressures. This
      leads to the high ideal selectivity of 1-butene/n-butane and ethene/ethane at
      relatively high pressure. It is also shown that the more C atoms present in the
      hydrocarbon molecules, the higher will be the permselectivity of alkenes relative
      to their corresponding saturated alkanes, which will be expected in the anhydrous
      Ag+-doped PSM. Copyright 1999 Academic Press.

PMID- 10072284
TI  - Microwave Dielectric Relaxation of Bound Water to Silica, Alumina, and Silica
      Alumina Gel Suspensions.
AB  - By the use of a time domain reflectomery method, dielectric measurements were
      carried out on silica, alumina, and silica-alumina gel suspensions (five types
      with composition varying between 0.3 < Si/Al atomic ratio <0.8) in the frequency
      range of 100 kHz to 20 GHz. For all the gels, a relaxation peak due to bound
      water was observed. This peak locates at around 1-10 MHz, indicating that the
      peak is a decade or 10 decades lower than those of biological polymers such as an
      aqueous DNA solution. The silica and alumina gels have a different bound water
      structure, judging from the fact that the peaks are different in their locations
      and shapes between the two gels. The silica-alumina gels exhibit two different
      peaks other than the peak of bulk water. The sum of the relaxation strength on
      the two peaks is proportional to the monolayer capacity obtained from water vapor
      isotherms. The shape of the one peak holds that of the silica gel, whereas the
      other retains that of alumina gel, and furthermore the ratio of the relaxation
      strength on the former peak to that on the latter depends on Si/Al atomic ratio.
      It is suggested that both peaks are caused by the orientation of bound water
      molecules. Copyright 1999 Academic Press.

PMID- 10072285
TI  - Effects of pH on Dielectric Relaxation of Montmorillonite, Allophane, and
      Imogolite Suspensions.
AB  - Dielectric measurements were performed on montmorillonite, allophane, and
      imogolite suspensions under various pH conditions, using time domain
      reflectometry over the frequency range 10 kHz-20 GHz. A dielectric relaxation
      peak due to bound water could be observed for all the clays. Allophane has two
      peaks, indicating that its peaks are very similar to those of silica-alumina
      gels. Although imogolite has a similar chemical composition, only one peak was
      found. The relaxation strength of montmorillonite is greater than that of the
      other two clays. For all the clays, the relaxation strength depended on the pH. A
      change in the relaxation strength according to a change in pH is explained in
      terms of the different network structures of the clay particles. It is suggested
      that bound water influences the network structure formation. In montmorillonite,
      a great relaxation process detected at low frequency is caused by surface
      polarization of counterions. The change in measure of the structural unit with
      the pH, identified from Schwartz's theory, has a tendency similar to that
      postulated by other experimental techniques, and surface charge densities
      identified are close to those estimated from CEC. Copyright 1999 Academic Press.

PMID- 10072286
TI  - Study of the Effect of Solubilized Gases on the Properties of Microemulsion
      Droplets.
AB  - The effect of dissolved gas (nitrogen, argon) on the properties of the droplets
      in water-in-oil and oil-in-water microemulsions (surfactant aggregation number,
      microviscosity, and micropolarity) has been investigated by means of time
      resolved fluorescence quenching and spectrofluorometry. This study extends a
      similar one on aqueous micellar solutions (R. G. Alargova et al., Langmuir 14,
      1575, 1998). The selected microemulsions were characterized by droplets of fairly
      large size and high volume fraction, in order to minimize the effect of the
      curvature of the surfactant layer and maximize the amount of gas that can be
      solubilized in the system. Within the experimental error, the investigated
      properties (surfactant aggregation number, intradroplet quenching rate constant
      which is related to the droplet microviscosity, and fluorescent probe lifetime
      and micropolarity) were found to be independent on whether the system was
      degassed, nitrogen-saturated, or argon-saturated, in the temperature range
      between 10 and 35 degrees C. The results confirm the conclusion reached in the
      above study; i.e., the effect of solubilized gases on the hydrophobic interaction
      which controls the formation of surfactant assemblies is extremely small and well
      below the sensitivity of the fluorescence probing techniques used in this
      investigation. Copyright 1999 Academic Press.

PMID- 10072287
TI  - Role of Electrostatic Repulsion on the Viscosity of Bidisperse Silica
      Suspensions.
AB  - The flow behavior of bidisperse aqueous silica suspensions has been studied at
      different electrolyte concentrations as a function of shear rate, total volume
      fraction of the particles, and volume ratio of small to large particles. It is
      shown that the range of the electrostatic repulsion plays an important role in
      determining the viscosity of the suspension. Binary mixtures of particles of
      longer range repulsive forces showed higher viscosities than the suspensions of
      shorter range electrostatic interactions. Bimodal suspensions of long-range
      interactions showed non-Newtonian behavior over wider ranges of shear due to the
      deformation of the ionic cloud around the particles, which is larger in these
      systems. The viscosity of bimodal suspensions used in this study was scaled with
      respect to the viscosity of the related monosized systems and the viscosity of
      one bimodal suspension at a fixed total volume fraction of the particles,
      employing our earlier scaling method. The model normalizes the effect of
      colloidal forces by introducing a scaling factor that collapses the data into a
      single curve for bimodal suspensions of a particular size ratio, and it is shown
      that the model is valid for systems with both short-range and long-range
      repulsive forces. Copyright 1999 Academic Press.

PMID- 10072288
TI  - Charge Adjustments upon Adsorption of a Weak Polyelectrolyte to a Mineral Oxide:
      The Hematite-Humic Acid System.
AB  - The proton adsorption to a mixture of purified Aldrich humic acid (PAHA) and
      hematite is investigated. Basic insight into the charge adjustment process is
      obtained by using a self-consistent-field lattice theory for polyelectrolyte
      adsorption. The calculations indicate that upon adsorption the component with the
      highest initial charge density tends to induce charges on the other component.
      The number of induced charges can show a maximum when the surface charge and the
      charge of the segments in direct contact with the surface roughly balance each
      other. Experimentally, the humic acid-hematite system is investigated by proton
      titrations. The alterations in charge density caused by adsorption of PAHA to
      hematite are investigated by comparing the proton adsorption on the individual
      samples with that on their mixtures. Upon adsorption a part of the functional
      groups of humic acid forms complexes with some of the surface sites of hematite.
      This interaction reduces the proton binding to the humic acid at relatively low
      pH and it promotes the proton adsorption on the oxide surface at relatively high
      pH. Copyright 1999 Academic Press.

PMID- 10072289
TI  - Adsorption Behaviors of CO2 and NH3 on Chemically Surface-Treated Activated
      Carbons.
AB  - The adsorption characteristics of activated carbon treated with 30 wt% HCl and 30
      wt% NaOH were investigated. The acid and base values were determined by Boehm's
      method and the surface structures were studied by the BET method with N2
      adsorption and iodine adsorption capacity. Also the adsorption properties of the
      activated carbons treated with acid and base chemical solutions were investigated
      with CO2 and NH3 adsorptions. Different adsorption behaviors of CO2 and NH3 on
      the modified activated carbons were observed, even though the physical surfaces
      of the activated carbons (i.e., specific surface area, pore size, and pore
      volume) were not significantly changed. Copyright 1999 Academic Press.

PMID- 10072290
TI  - Interaction of Diphenylamine Diazonium Salt with Sodium Dodecyl Sulfate in
      Aqueous Solution.
AB  - The interaction of diphenylamine-4-diazonium salt (DDS) with sodium dodecyl
      sulfate (SDS) in aqueous solution was investigated. The results show that in a
      2.1-2.3 molar ratio of SDS/DDS, the solution viscosity increases suddenly to a
      thousand times the original and then drops rapidly as the ratio beyond the
      region. The dramatic increase in the viscosity was proposed to be due to
      aggregated micelles that form in solution due to the interaction of diphenylamine
      diazonium salt and micelles formed from SDS, and when further SDS was added drops
      rapidly, because the aggregated micelles were separated by the electrostatic
      repulsion force originated from the overfeeding of SDS. It is interesting that
      the viscosity of the solution is very susceptible to UV light, i.e., the
      increased viscosity decreases gradually when the solution was exposed under UV
      light because the irradiation decomposes the diazonium group. The influence of
      [SDS] and the ratio of SDS/DDS on the viscosity of the solution were also
      investigated. Copyright 1999 Academic Press.

PMID- 10072291
TI  - Preparation of Nanosize Tin Oxide Particles from Water-in-Oil Microemulsions.
AB  - Nanoparticles of tin oxide (SnO2) have been prepared from water-in-oil
      microemulsions consisting of water, AOT (surfactant), and n-heptane (oil).
      Precursor hydroxides were precipitated in the aqueous cores of water-in-oil
      microemulsions and then calcined at 600 degrees C for 2 h to form tin oxide
      powder. The formation of phase pure tin oxide was confirmed by means of X-ray
      diffraction analysis. The tin oxide powder was found to be less than 40 nm in
      particle diameter and to have a higher specific surface area, about 73 m2/g, when
      compared with tin oxide powder prepared through the conventional precipitation
      method (19 m2/g). Copyright 1999 Academic Press.

PMID- 10072292
TI  - Constitutive expression of GAP-43 correlates with rapid, but not slow regrowth of
      injured dorsal root axons in the adult rat.
AB  - It has been postulated that the neuronal growth-associated protein GAP-43 plays
      an essential role in axon elongation. Although termination of developmental axon
      growth is generally accompanied by a decline in expression of GAP-43, a
      subpopulation of dorsal root ganglion (DRG) neurons retains constitutive
      expression of GAP-43 throughout adulthood. Peripheral nerve regeneration
      occurring subsequent to injury of the peripheral axon branches of adult DRG
      neurons is accompanied by renewed elevation of GAP-43 expression. Lesions of DRG
      central axon branches in the dorsal roots are also followed by some regenerative
      growth, but little or no increase in GAP-43 expression above the constitutive
      level is observed. To determine whether dorsal root axon regeneration occurs only
      from neurons which constitutively express GAP-43, we have used retrograde
      fluorescent labeling to identify those DRG neurons which extend axons beyond a
      crush lesion of the dorsal root. Only GAP-43 immunoreactive neurons supported
      axon regrowth of 7 mm or greater within the first week. At later times, axon
      regrowth is seen to occur from neurons both with and without GAP-43
      immunoreactivity. We conclude that regeneration of injured axons within the
      dorsal root is not absolutely dependent on the presence of GAP-43, but that
      expression of GAP-43 is correlated with a capacity for rapid growth.

PMID- 10072293
TI  - Intranigral transplants of GABA-rich striatal tissue induce behavioral recovery
      in the rat Parkinson model and promote the effects obtained by intrastriatal
      dopaminergic transplants.
AB  - Intrastriatal transplantation of fetal ventral mesencephalon (VM) is currently
      explored as a potential clinical therapy in Parkinson's disease (PD). Although
      providing substantial benefit for the patient, behavioral recovery so far
      obtained with intrastriatal VM grafts is not complete. Using the 6
      hydroxydopamine lesion model of PD, we show here that near-complete restoration
      of the striatal dopamine (DA) innervation can be achieved by multiple
      intrastriatal microtransplants of fetal DA cells; nevertheless, complete recovery
      in complex sensorimotor behaviors was not obtained in these animals. In line with
      the current model of basal ganglia function, this suggests that the lesion
      induced overactivity of the basal ganglia output structures, i.e., the substantia
      nigra (SN) and the entopeduncular nucleus, may not be completely reversed by
      intrastriatal VM grafts. In the present study, we have transplanted fetal VM
      tissue or fetal striatal tissue, as a source of DA and GABA neurons,
      respectively, into the SN of DA-depleted rats. Intranigral VM grafts induced
      behavioral recovery in some sensorimotor behaviors (forelimb akinesia and balance
      tests), but the effect did not exceed the recovery observed after intrastriatal
      VM grafts. Intranigral grafts of striatal tissue induced a pattern of functional
      recovery which was distinctly different from that observed after intranigral VM
      grafts, and recovery in coordinated forelimb use in the paw-reaching test was
      even more pronounced than after intrastriatal transplantation of VM cells.
      Combined transplantation of DA neurons into the striatum and GABA-rich striatal
      neurons into the SN induced additive effects of behavioral recovery observed in
      the forelimb akinesia test. We propose that intranigral striatal transplants, by
      a GABA-mediated inhibitory action, can reduce the overactivity of the host SN
      projection neurons and can induce significant recovery in complex motor behavior
      in the rat PD model and that such grafts may be used to increase the overall
      functional efficacy of intrastriatal VM grafts.

PMID- 10072294
TI  - Postictal blockade of ischemic hippocampal neuronal death in primates using
      selective cathepsin inhibitors.
AB  - This paper is to study the participation of cathepsin in ischemic neuronal death
      of the monkey hippocampal cornu ammonis (CA) 1 sector and also to clarify whether
      its selective inhibitor epoxysuccinyl peptides such as CA-074 and E-64c can
      inhibit the neuronal death or not. In the preceding reports, we demonstrated mu
      calpain activation and subsequent rupturing of the lysosomal membrane of
      postischemic CA1 neurons and also increase of enzyme activity of cathepsins B and
      L in monkeys undergoing a complete 20-min whole brain ischemia. Here,
      morphological, immunohistochemical and enzymatical analyses were performed to
      examine the efficacy of two selective cathepsin inhibitors in the postictal
      blockade of delayed neuronal death in the monkey hippocampus. Both inhibitors
      could significantly decrease enzyme activities of cathepsins B and L in all
      hippocampal sectors. When CA-074 was intravenously administered immediately after
      the ischemic insult, approximately 67% of CA1 neurons were saved from delayed
      neuronal death on day 5 after ischemia. In contrast, when E-64c was similarly
      administered, approximately 84% of CA1 neurons were saved from delayed neuronal
      death on day 5. The surviving neurons showed mild central chromatolysis and
      negligible immunoreactivity for cathepsins B and L. These observations indicate
      that the use of cathepsin inhibitors may become novel strategy for prevention of
      ischemic delayed neuronal death in the primate hippocampus.

PMID- 10072295
TI  - Expanded polyglutamine domain proteins bind neurofilament and alter the
      neurofilament network.
AB  - Eight inherited neurodegenerative diseases are caused by genes with expanded CAG
      repeats coding for polyglutamine domains in the disease-producing proteins. The
      mechanism by which this expanded polyglutamine domain causes neurodegenerative
      disease is unknown, but nuclear and cytoplasmic polyglutamine protein aggregation
      is a common feature. In transfected COS7 cells, expanded polyglutamine proteins
      aggregate and disrupt the vimentin intermediate filament network. Since neurons
      have an intermediate filament network composed of neurofilament (NF) and NF
      abnormalities occur in neurodegenerative diseases, we examined whether pathologic
      length polyglutamine domain proteins also interact with NF. We expressed varying
      lengths polyglutamine-green fluorescent protein fusion proteins in a neuroblast
      cell line, TR1. Pathologic-length polyglutamine-GFP fusion proteins formed large
      cytoplasmic aggregates surrounded by neurofilament. Immunoisolation of pathologic
      length polyglutamine proteins coisolated 68-kDa NF protein demonstrating
      molecular interaction. These observations suggest that polyglutamine interaction
      with NF is important in the pathogenesis of the polyglutamine repeat diseases.

PMID- 10072297
TI  - Eukaryotic initiation factor 2alpha kinase and phosphatase activity during
      postischemic brain reperfusion.
AB  - When ischemic brain is reperfused, there is in vulnerable neurons immediate
      inhibition of protein synthesis associated with a large increase in
      phosphorylation of the alpha-subunit of eukaryotic initiation factor 2
      [eIF2alpha, phosphorylated form eIF2alpha(P)]. We examined eIF2alpha kinase and
      eIF2alpha(P) phosphatase activity in brain homogenate postmitochondrial
      supernatants obtained from rats after 3 to 30 min of global brain ischemia
      (cardiac arrest), after 5 min of ischemia and 5 min of reperfusion (5R), and
      after 10 min of ischemia and 90 min reperfusion (90R). Because it has been
      suggested that PKR might be specifically responsible for producing eIF2alpha(P)
      during reperfusion, we also examined in brain homogenates from wild-type and
      PKR0/0 C57BL/6J x 129/SV mice the effect of 5 min of ischemia and 5 min of
      reperfusion on eIF2alpha(P). Cytosolic brain eIF2alpha(P) in the 5R and 90R rats
      was 18- and 23-fold that of nonischemic controls without any change in the rate
      of eIF2alpha(P) dephosphorylation. There was no change in eIF2alpha kinase
      activity between 3 and 30 min of ischemia but an 85% decrease in the 5R group;
      the 90R group was similar to controls. In wild-type and PKR0/0 mice total
      eIF2alpha was identical, and there was an identical 16-fold increase in
      eIF2alpha(P) at 5 min of reperfusion. Our observations contradict hypotheses that
      PKR activation, loss of eIF2alpha(P) phosphatase activity, or any general
      increase in eIF2alpha kinase activity are responsible for reperfusion-induced
      phosphorylation of eIF2alpha, and we suggest that the mechanism may involve
      regulation of the availability of eIF2alpha to a kinase.

PMID- 10072296
TI  - Effect of repeated L-DOPA, bromocriptine, or lisuride administration on
      preproenkephalin-A and preproenkephalin-B mRNA levels in the striatum of the 6
      hydroxydopamine-lesioned rat.
AB  - Abnormal involuntary movements, or dyskinesias, plague current symptomatic
      approaches to the treatment of Parkinson's disease. The neural mechanisms
      underlying the generation of dyskinesia following repeated l-3,4
      dihydroxyphenylalanine (L-DOPA) or dopamine agonist administration in Parkinson's
      disease remain unknown. However, de novo administration of bromocriptine or
      lisuride to either l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates
      or patients can alleviate parkinsonian symptoms without the development of
      dyskinesia. In this study, we have investigated behavioral responses and
      alterations in the expression of opioid neuropeptide precursors preproenkephalin
      A (PPE-A, encoding methionine- and leucine-enkephalin) and preproenkephalin-B
      (PPE-B), the precursor encoding dynorphins (dynorphin A1-17 and B1-13, leucine
      enkephalin, and alpha-neoendorphin) in striatal output pathways of the 6
      hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. Expression
      was assessed following repeated L-DOPA, bromocriptine, or lisuride
      administration. Given the functional organization of basal ganglia circuitry into
      anatomically discrete parallel circuits, we investigated alterations in peptide
      expression with reference to the detailed topography of the striatum. Following
      repeated L-DOPA administration (6.5 mg/kg, b.d., 21 days) in the 6-OHDA-lesioned
      rat a rotational response was observed. This became markedly enhanced with
      repeated treatment. We have previously characterized the pharmacology of this
      enhanced response and have suggested that it is a useful model for the
      elucidation of the cellular and molecular mechanisms underlying L-DOPA- and
      dopamine agonist-induced dyskinesia. In contrast to l-DOPA, de novo
      administration of bromocriptine (1 or 5 mg/kg, b.d., 21 days) or lisuride (0.01
      or 0.1 mg/kg, b.d., 21 days) did not lead to an enhanced behavioral response. In
      vehicle-treated, 6-OHDA-lesioned animals, PPE-A expression was elevated rostrally
      and dorsally, while PPE-B expression was reduced in the striatum at all
      rostrocaudal levels. Repeated l-DOPA administration was accompanied by elevations
      in striatal PPE-B mRNA levels and a further elevation, above lesion-induced
      levels, in PPE-A expression. This further elevation was restricted to the
      dorsolateral striatum. However, following repeated bromocriptine or lisuride
      administration no increase in PPE-B expression was observed and the lesion
      induced increase in PPE-A expression was normalized to prelesion levels.
      Increased PPE-A and PPE-B levels may, through decreasing GABA and glutamate
      release, respectively, in output nuclei of the basal ganglia, play a role in the
      development of L-DOPA- and dopamine-agonist induced dyskinesia in Parkinson's
      disease. These studies suggest that anti-parkinsonian treatments which are not
      associated with an elevation in PPE-B and/or normalize elevated PPE-A precursor
      expression, such as NMDA-receptor antagonists or long-acting dopamine D2 receptor
      agonists, e.g., cabergoline or ropinirole, may reduce dyskinesia in Parkinson's
      disease.

PMID- 10072298
TI  - A key role for GAP-43 in the retinotectal topographic organization.
AB  - To have a proper spatial visual perception, vertebrate retinal ganglion cells
      connect to their brain targets in a highly ordered fashion. The molecular bases
      for such topographic retinotectal connection in mammals still remain largely
      unknown. Using the gene knock-out approach in mice, we report here a key role for
      the GAP-43 growth cone protein in the development of the visual system. In mice
      bearing a targeted disruption of GAP-43 exon 1, a high proportion of retinal
      ganglion cell (RGC) axons was found to grow abnormally into the ipsilateral optic
      tract and into the hypothalamus. After leaving the optic chiasm during
      development, the GAP-43-deficient RGC axons generally follow the optic tracts but
      are unable to form proper terminal zones in the lateral geniculate nucleus.
      Moreover, in the superior colliculus, RGC axons lacking GAP-43 are intermingled.
      These results suggest an essential role for GAP-43 in development of the
      topographic retinotectal connection.

PMID- 10072299
TI  - Beneficial effects of lysine acetylsalicylate, a soluble salt of aspirin, on
      motor performance in a transgenic model of amyotrophic lateral sclerosis.
AB  - We have studied the effect of lysine acetylsalicylate (LAS; Aspegic), a soluble
      salt of aspirin, on motor deficits in transgenic mice expressing a human
      superoxide dismutase SOD1 mutation (Gly-93 --> Ala), an animal model of familial
      amyotrophic lateral sclerosis (FALS). In nontreated FALS mice, motor impairments
      appear at 12-14 weeks of age, whereas paralysis is not observed before 20 weeks
      of age. Life expectancy is 140-170 days. Early treatment with LAS from 5 weeks of
      age delayed the appearance of motor deficits in FALS mice as measured by
      extension reflex, loaded grid, and rotarod tests. This beneficial effect of
      treatment was maintained up to 18 weeks of age, until just before onset of end
      stage disease. When treatment was started at 13 weeks, no significant beneficial
      effect was observed. These results demonstrate that chronic LAS treatment is able
      to delay the appearance of reflex, coordination, and muscle strength deficits in
      this animal model of ALS if the treatment is started early enough. However,
      neither the onset of paralysis nor end-stage disease were improved by the LAS
      treatment. In the absence of an effect on survival, the functional improvement
      demonstrated here is probably the maximum that this demanding model could allow.
      Although other properties of LAS may have contributed to its beneficial effect,
      we suggest that the antioxidant properties of aspirin are responsible for the
      positive effects in this model and support the use of antioxidants as effective
      therapy for ALS.

PMID- 10072300
TI  - Activated alpha2macroglobulin increases beta-amyloid (25-35)-induced toxicity in
      LAN5 human neuroblastoma cells.
AB  - The presence of the alpha2macroglobulin receptor/low density lipoprotein receptor
      related protein (alpha2Mr/LRP) and its ligands alpha2macroglobulin (alpha2M),
      apoliprotein E, and plasminogen activators was detected in senile plaques of
      Alzheimer's disease (AD). To explore a possible role of alpha2M in
      neurodegenerative processes occurring in AD, we analyzed the effect of alpha2M on
      Abeta 25-35-induced neurotoxicity. Treatment of LAN5 human neuroblastoma cells
      with 10 microM beta-amyloid peptide fragment 25-35 (Abeta 25-35) for 72 h
      resulted in a 50% decrease in cell viability as determined by MTT incorporation
      and cell counts. The addition of alpha2M to the culture medium of these cells did
      not determine any effect, but when the activated form alpha2M* was used a dose
      dependent decrease in cell viability was observed, the maximum effect being
      reached at 140 and 280 nM. Moreover, treatment of LAN5 cells with alpha2M* in
      combination with Abeta 25-35 increased the neurotoxicity of the amyloid peptide
      by 25%. This neurotoxic effect of alpha2M* seems to be related to its capability
      to bind and inactivate TGFbeta in the culture medium, since it was mimicked by a
      TGFbeta neutralizing antibody. A possible involvement of receptor-mediated
      endocytosis was ruled out, since alpha2M receptor is not present on LAN5, as
      revealed by RT-PCR and Western blotting experiments. The presence of alpha2M* in
      amyloid deposits of Alzheimer's disease has been recently reported and a possible
      impairment of LRP internalization processes has been hypothesized. Our data
      suggest that the local accumulation of alpha2M* in AD plaques may increase Abeta
      25-35-induced neurotoxicity by neutralizing TGFbeta-mediated neuroprotective
      mechanisms.

PMID- 10072301
TI  - Long-term estrogen replacement coordinately decreases trkA and beta-PPT mRNA
      levels in dorsal root ganglion neurons.
AB  - Estrogen status has profound effects on cutaneous sensitivity in adult female
      rats. The presence of alpha-estrogen receptor mRNA and protein in NGF-dependent,
      adult female rat dorsal root ganglion (DRG) neurons raises the possibility that
      estrogen modulates cutaneous sensation by acting directly on primary afferent
      neurons, perhaps by altering their sensitivity to NGF. The present study examined
      the effect of long-term (90 days) daily injections of an estrogen preparation,
      Premarin (Wyeth-Ayerst, Radnor, PA), to ovariectomized adult rats on lumbar DRG
      high-affinity NGF receptor, trkA, mRNA levels, and on beta-preprotachykinin (beta
      PPT) mRNA levels, which have been shown to be regulated by NGF. Two doses were
      used in the experiments, the higher dose being 10 times that of the lower dose.
      Such injections had an effect opposite that reported for short-term, acute
      estrogen treatment on DRG trkA mRNA levels. The current data show that long-term
      daily estrogen treatment decreases trkA mRNA levels by 36%. After 90 days of
      estrogen treatment, no dose effect was evident. Moreover, as would be expected if
      beta-PPT gene expression is regulated by NGF through the trkA receptor, long-term
      estrogen treatment decreased DRG neuronal beta-PPT mRNA levels by about 30%. As
      with trkA, there was no dose effect evident after 90 days of estrogen treatment.
      These data suggest the possibility that estrogen modulates DRG neuropeptide gene
      expression and, perhaps, cutaneous sensitivity by regulating NGF receptor gene
      expression.

PMID- 10072302
TI  - Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter.
AB  - MPTP has been shown to induce parkinsonism both in human and in nonhuman
      primates. The precise mechanism of dopaminergic cell death induced following MPTP
      treatment is still subject to intense debate. MPP+, which is the oxidation
      product of MPTP, is actively transported into presynaptic dopaminergic nerve
      terminals through the plasma membrane dopamine transporter (DAT). In this study,
      we used mice lacking the DAT by homologous recombination and demonstrated that
      the MPTP-induced dopaminergic cell loss is dependent on the presence of the DAT.
      For this we have used tyrosine hydroxylase immunoreactivity (TH-IR) labeling of
      dopamine cells of the substantia nigra compacta in wild-type, heterozygote, and
      homozygote mice that were given either saline or MPTP treatments (two ip
      injections of 30 mg/kg, 10 h apart). Our results show a significant loss of TH-IR
      in wild type (34.4%), less loss in heterozygotes (22.5%), and no loss in
      homozygote animals. Thus dopamine cell loss is related to levels of the DAT.
      These results shed light on the degenerative process of dopamine neurons and
      suggest that individual differences in developing Parkinson's disease in human
      may be related to differences of uptake through the DAT of a yet unidentified
      neurotoxin.

PMID- 10072303
TI  - Effects of basic fibroblast growth factor (bFGF)-neutralizing antibody and
      platelet factor 4 on facial nerve regeneration.
AB  - Exogenous basic fibroblast growth factor (bFGF) has been shown to prevent death
      of injured cholinergic neurons and stimulate neurite outgrowth from the proximal
      stump of the transected sciatic nerve. The present study was designed to examine
      the role of endogenous bFGF, rather than exogenous bFGF in the regenerative
      process of the transected facial nerve of guinea pig, by using the so-called
      silicone tubulization model which enabled us to bridge the transected facial
      nerve with a silicone tube and to inject into the tube bFGF-neutralizing
      antibody, normal IgG, saline, or platelet factor 4 (an antagonist for bFGF
      receptor). Under light microscopy, treatment with bFGF-neutralizing antibody
      caused significant decreases in vascular number, vascular area, and regenerating
      axons in the middle point of regeneration chambers at the third week after facial
      nerve transection, even though electron microscopy revealed that the bFGF
      neutralizing antibody increased the number of thin axons with caliber smaller
      than 1 micrometer. Treatment with platelet factor 4 exhibited similar but more
      conspicuous effects on facial nerve regeneration. These findings suggest that
      endogenous bFGF not only facilitates angiogenesis within the transected facial
      nerve but also acts as a neurotrophic agent during facial nerve regeneration; it
      appears that endogenous bFGF contributes to the enlargement of axon caliber and
      increases the number of relatively large caliber axons.

PMID- 10072304
TI  - Inhibition of sensory neuron apoptosis and prevention of loss by NT-3
      administration following axotomy.
AB  - Following permanent transection of their peripheral axons, a proportion of adult
      rat dorsal root ganglion neurons undergo programmed cell death (apoptosis) over a
      period of months. The underlying causes of this neuron loss are unclear, but may
      involve the interruption of the supply of target-derived neurotrophic factors,
      the replacement of which could prevent this loss from occurring. To investigate
      whether the administration of neurotrophic factors can prevent the dorsal root
      ganglion neuron death in adults, a 1 mg/ml solution of ciliary neurotrophic
      factor or of NT-3 was applied via a silicon reservoir to the proximal stump after
      unilateral sciatic transection at mid-thigh level. The incidence of apoptotic
      neurons and neuronal loss in the L4 and L5 ganglia ipsilateral to sciatic nerve
      transection when compared with the contralateral ganglia was then measured 1
      month later. This was assessed by examining serial sections of ganglia for
      neurons undergoing apoptosis and expressing the total counted as a percentage of
      the total number of neurons estimated using a stereological neuron counting
      technique. Our results show that NT-3 administration significantly reduced the
      incidence of apoptotic neurons and prevented neuron loss, while CNTF had no
      effect on either parameter.

PMID- 10072305
TI  - Effect of precollicular transection on audiogenic seizures in genetically
      epilepsy-prone rats.
AB  - Previous studies have demonstrated that generalized tonic-clonic seizures (GTCS)
      consisting of running/bouncing clonic and tonic extension can still be elicited
      in rats after brain transections which separate forebrain from brain stem,
      showing that forebrain circuitry is not required for GTCS. Inasmuch as sound
      induced generalized tonic-clonic seizures in rodents are characterized by running
      bouncing clonic and tonic convulsions, we have hypothesized that these are brain
      stem seizures that can occur independently of the forebrain. To test this
      hypothesis, we examined the response of two strains of genetically epilepsy-prone
      rats (GEPR-3s and GEPR-9s) to seizure-evoking auditory stimuli 3 h after a
      precollicular transection or sham surgery performed under ether anesthesia. In
      addition, the effect of a precollicular transection on audiogenic seizures was
      evaluated in normal rats made susceptible to such seizures by infusing NMDA into
      the inferior colliculus. Following the transection 58% of GEPR-9s displayed a
      sound-induced tonic-clonic convulsion and the remaining 42% exhibited a sound
      induced seizure when subjected to stimulation 5 min after a subconvulsant dose of
      pentylenetetrazol (PTZ). While sham surgery and the precollicular transection
      both reduced sound-induced seizure severity in GEPR-3s, the full seizure response
      could be elicited by sound stimulation following a subconvulsant dose of PTZ.
      Moreover, the audiogenic seizures in normal rats rendered susceptible by NMDA
      were unaltered by the precollicular transection. These findings show that the
      anatomical circuitry required for generalized tonic-clonic seizures evoked by
      sound stimulation in rodents resides within the brain stem.

PMID- 10072306
TI  - The endoplasmic reticulum stress-responsive protein GRP78 protects neurons
      against excitotoxicity and apoptosis: suppression of oxidative stress and
      stabilization of calcium homeostasis.
AB  - The 78-kDa glucose-regulated protein (GRP78) is localized in the endoplasmic
      reticulum (ER), and its expression is increased by environmental stressors in
      many types of nonneuronal cells. We report that levels of GRP78 are increased in
      cultured rat hippocampal neurons exposed to glutamate and oxidative insults (Fe2+
      and amyloid beta-peptide) and that treatment of cultures with a GRP78 antisense
      oligodeoxynucleotide increases neuronal death following exposure to each insult.
      GRP78 antisense treatment enhanced apoptosis of differentiated PC12 cells
      following NGF withdrawal or exposure to staurosporine. Pretreatment of
      hippocampal cells with 2-deoxy-d-glucose, a potent inducer of GRP78 expression,
      protected neurons against excitotoxic and oxidative injury. GRP78 expression may
      function to suppress oxidative stress and stabilize calcium homeostasis because
      treatment with GRP78 antisense resulted in increased levels of reactive oxygen
      species and intracellular calcium following exposure to glutamate and oxidative
      insults in hippocampal neurons. Dantrolene (a blocker of ER calcium release),
      uric acid (an antioxidant), and zVAD-fmk (a caspase inhibitor) each protected
      neurons against the death-enhancing action of GRP78 antisense. The data suggest
      that ER stress plays a role in neuronal cell death induced by an array of insults
      and that GRP78 serves a neuroprotective function.

PMID- 10072307
TI  - Cortical ablation induces a spreading calcium-dependent, secondary pathogenesis
      which can be reduced by inhibiting calpain.
AB  - Many forms of acute brain injury are associated with a secondary, glutamate- and
      calcium-dependent cascade which greatly exacerbates the final damage. The calcium
      dependent protease, calpain, has been implicated as an important variable in this
      pathogenic process. The present studies tested (i) if similar secondary
      degeneration occurs following surgical ablation of a discrete area within rat
      visual cortex, (ii) if activation of calpain contributes to the secondary
      degeneration by spreading into areas adjacent to the ablation, and (iii) if
      blocking calpain's proteolytic effects reduces the secondary degeneration
      attendant to the lesion. Antibodies selective for a protein fragment specifically
      generated by calpain were used to map areas in which the protease had been
      activated. Labeling was present 5 min after surgery in a narrow zone surrounding
      the ablated region. The volume of the immunopositive staining increased twofold
      within 24 h and fivefold by 48 h, at which time it was equivalent in size to the
      original lesion. This staining pattern significantly decreased in size at 5 days
      postsurgery. Application of calpain inhibitors to the ablation site immediately
      after surgery reduced the spread of calpain activation by approximately 80%.
      Following cortical ablation, the volume of the lateral geniculate nucleus
      ipsilateral to the cortical ablation shrank by 46 +/- 3% in control rats but only
      by 31 +/- 5% in animals given the calpain inhibitors. These results establish
      that (i) a secondary degenerative cascade is unleashed following discrete
      cortical surgery which expands into brain areas clearly outside the initial
      perturbation site, (ii) the gradual expansion of calpain activation contributes
      to the underlying secondary pathology, and (iii) blocking calpain activity
      substantially reduces atrophy in areas anatomically connected, but physically
      distal to the damaged zone. The possible utility of topical applications of
      calpain inhibitors, or analogously acting drugs, in minimizing the secondary
      effects of brain surgery is discussed.

PMID- 10072309
TI  - Meeting announcement 

PMID- 10072308
TI  - Denervation of the skin following section of the inferior alveolar nerve leads to
      increased NGF accumulation without change in NGF mRNA expression.
AB  - Following inferior alveolar nerve section and capping of the nerve to prevent
      regeneration, amounts of nerve growth factor (NGF) and NGF mRNA have been
      quantified in the chin skin, a discrete target of the nerve. NGF protein in the
      target region increases rapidly following nerve section and to levels known to
      induce sprouting. NGF on the ipsilateral side increased many-fold above
      unoperated control and the contralateral side also increased above control.
      Measurement of NGF mRNA levels using quantitative Northern analysis revealed,
      however, that there was no change in the expression levels of NGF mRNA,
      indicating that the large increase in protein occurs due to a cessation of
      transport back to the cell bodies of the innervating neurons.

PMID- 10072310
TI  - Variations on an Expectancy-Value Model of Motivation in Science.
AB  - Relationships among motivational variables from goal theory and expectancy-value
      theory were investigated in this correlational study of high school students.
      Self-report surveys of motivation in science were collected during biology
      classes from 69 males and 80 females. Outcome measures were effort, persistence,
      and achievement. Gender differences were noted in the pattern of zero-order
      correlations. Internal motivation variables were related to achievement in males
      but not females. Regression analyses indicated that the motivation variables
      explained large proportions of variance in the outcomes. However, the
      contribution of individual variables differed by gender. Most notable was
      perceived ability, which contributed significantly to predicting outcome measures
      for females but not males. Findings suggest that interventions may need to focus
      on different motivational aspects depending on gender. Copyright 1999 Academic
      Press.

PMID- 10072311
TI  - Utilization of Illustrations during Learning of Science Textbook Passages among
      Low- and High-Ability Children.
AB  - Effects of illustrations on learning authentic textbook materials were studied
      among 10-year-old elementary school children of high and low intellectual
      ability. Experiment 1 showed that the presence of illustrations improved learning
      of illustrated text content, but not that of nonillustrated text content.
      Comprehension scores were improved by the presence of illustrations for high
      ability children, but not for low-ability children. In Experiment 2, children's
      eye movements were measured during learning of illustrated textbook passages to
      study how children divide their attention between text and illustrations. The
      results suggest that learning is heavily driven by the text and that children
      inspect illustrations only minimally. High-ability students were more strategic
      in processing in the sense that they spent relatively more time on pertinent
      segments of text and illustrations. It is concluded that the learning of
      illustrated science textbook materials involves requirements that may be more
      readily met by more intellectually capable students. Copyright 1999 Academic
      Press.

PMID- 10072312
TI  - Self-Efficacy, Motivation Constructs, and Mathematics Performance of Entering
      Middle School Students.
AB  - The objectives of this study were to determine the influence of various
      motivation variables on task-specific mathematics performance and to explore
      whether these variables change during the first year of middle school (N = 273).
      Students' task-specific self-efficacy was the only motivation variable to predict
      performance and did so both at start and end of year. There were no differences
      in anxiety, self-concept, or self-efficacy for self-regulation between start and
      end of year, but, by end of year, students described mathematics as less valuable
      and reported lower effort and persistence. Gifted students had stronger
      mathematics self-concept beliefs, and they had more accurate and less
      overconfident self-efficacy beliefs than did regular education students. There
      were no gender differences in any of the motivation constructs. Copyright 1999
      Academic Press.

PMID- 10072313
TI  - The Relationship between Children's Emotional and Behavioral Problems and the
      Social Responses of Elementary School Teachers.
AB  - This study examined the relationship between children's emotional and behavioral
      problems and teachers' social responding. Elementary school students completed
      the Children's Depression Inventory and a parent completed the Child Behavior
      Checklist. Teachers rated children on measures of interpersonal attractiveness
      and personal rejection. Teachers' ratings of student interpersonal attractiveness
      were significantly correlated with the level of student depression, internalizing
      problems, externalizing problems, and overall psychopathology. However, teachers'
      ratings of personal rejection toward students only correlated with externalizing
      behavior problems. Family income was also related to child adjustment and teacher
      ratings. Externalizing behavior problems best predicted both lower interpersonal
      attractiveness and increased personal rejection, even after controlling for
      family income. Copyright 1999 Academic Press.

PMID- 10072314
TI  - Time Limitations Enhance Reading Comprehension.
AB  - Few studies in the domain of reading have explored the relation between time
      limitations and reading comprehension. Time limitations may enhance reading
      comprehension by promoting mindfulness in students, a construct which involves
      exertion of more effort and motivation. This study explored the effects of time
      constraints on reading comprehension in adult readers. Mild time constraints
      should create greater mindfulness in readers, resulting in enhanced
      comprehension. College students read passages under no time pressure, under mild
      time pressure, or under severe time pressure. Reading comprehension was assessed
      in each condition. The best reading comprehension was observed under mild time
      pressure. Implications are discussed. Copyright 1999 Academic Press.

PMID- 10072316
TI  - Microconidia of Neurospora crassa.
AB  - Neurospora crassa produces two types of vegetative spores-relatively small
      numbers of uninucleate microconidia and very large numbers of multinucleate
      macroconidia (blastoconidia and arthroconidia). The microconidia can function
      either as spermatia (male gametes) or as asexual reproductive structures or both.
      In nature they probably function exclusively in fertilization of protoperithecia.
      The environmental conditions favoring their formation and the pattern of their
      development are quite distinct from those of macroconidia. Mutants of N. crassa
      have been isolated in which macroconidiation is selectively blocked without
      affecting microconidiation, showing that these two types of conidial
      differentiation involve distinct developmental pathways. Unlike microconidia of
      some related ascomycetes, those of Neurospora are capable of germination,
      providing viable uninucleate haploid cells which are desired in several types of
      investigations. A technique of selectively removing macroconidia from culture
      initiated on cellophane overlying agar medium allows pure microconidia to be
      obtained even from the wild-type strains of Neurospora. The conditional
      microcyclic strain, mcm, allows either macroconidia or microconidia to be
      obtained at will, depending on the conditions of culture. The new methods of
      obtaining pure microconidia from normal laboratory strains will make it quick and
      easy to purify heterokaryotic transformants following introduction of DNA into
      multinucleate protoplasts. Moreover, these methods allow the detection of genetic
      variability that remains hidden within an individual fungus and the estimation of
      the frequency of nuclear types in laboratory-constructed heterokaryons. The
      discovery, function, and development of microconidia are described and their
      research applications are discussed in this review.

PMID- 10072317
TI  - A G protein alpha subunit from Cochliobolus heterostrophus involved in mating and
      appressorium formation.
AB  - A Galpha subunit-encoding gene (CGA1) was cloned from Cochliobolus
      heterostrophus, a heterothallic foliar pathogen of corn. The deduced amino acid
      sequence showed similarity to Galpha proteins from other filamentous fungi and
      suggested that CGA1 is a member of the Galphai class. cga1 mutants had reduced
      ability to form appressoria on glass surfaces and on corn leaves; mutants
      nevertheless caused lesions on corn plants like those of wild type. cga1 mutants
      were female sterile; sexual development was completely abolished when the mutant
      allele was homozygous in a cross. Ascospores produced in crosses heterozygous at
      Cga1 were all wild type. The signal transduction pathway represented by CGA1
      appears to be involved in developmental pathways leading to either appressorium
      formation or mating; in sexual development CGA1 is required for both fertility
      and ascospore viability.

PMID- 10072318
TI  - Regulation of dikaryon-expressed genes by FRT1 in the basidiomycete Schizophyllum
      commune.
AB  - The gene FRT1 has previously been shown to induce homokaryotic fruiting in
      transformation recipients of the basidiomycete Schizophyllum commune. In this
      paper, we demonstrate by gene disruption experiments that FRT1 is dispensable for
      dikaryotic fruiting. Nonfruiting homokaryotic FRT1 disruptant strains exhibited
      enhanced aerial growth of mycelia compared to wild type. Introduction of a
      functional FRT1 allele into the disruptant restored the wild-type colony
      morphology. Transcript abundance of the dikaryon-expressed SC1 and SC4
      hydrophobin genes and the SC7 gene were greatly elevated in homokaryotic FRT1
      disruptant strains. Growth of the disruptant strains under continuous light was
      found to inhibit the elevation of SC1 and SC4 transcript levels, but not of SC7
      mRNA. These data suggest that the role of FRT1 in vegetatively growing
      homokaryons is to act as a negative regulator of dikaryon-expressed genes.

PMID- 10072319
TI  - Positive regulation of adenylyl cyclase activity by a galphai homolog in
      Neurospora crassa.
AB  - GNA-1 and GNA-2 are two G protein alpha subunits from the filamentous fungus
      Neurospora crassa. Loss of gna-1 leads to multiple phenotypes, while Deltagna-2
      strains do not exhibit visible defects. However, Deltagna-1Deltagna-2 mutants are
      more affected in Deltagna-1 phenotypes. Here we report a biochemical
      investigation of the roles of GNA-1 and GNA-2 in cAMP metabolism. Assays of Mg2+
      ATP-dependent adenylyl cyclase activity (+/-GppNHp) in extracts from submerged
      cultures indicated that Deltagna-2 strains were normal, whereas Deltagna-1 and
      Deltagna-1Deltagna-2 strains had only 10-15% the activity of the wild-type
      control. Levels of the Gbeta protein, GNB-1, were normal in Deltagna-1 strains,
      excluding altered GNB-1 production as a factor in loss of adenylyl cyclase
      activity. Steady-state cAMP levels in Deltagna-1 and Deltagna-1Deltagna-2 mutants
      were reduced relative to wild-type under conditions that result in morphological
      abnormalities (solid medium), while levels in submerged culture were normal. cAMP
      phosphodiesterase activities in submerged cultures of Deltagna-1 and/or Deltagna
      2 strains were lower than in wild-type; the individual deletions were additive in
      decreasing activity. These results suggest that in submerged culture, N. crassa,
      like mammalian systems, possesses compensatory mechanisms that maintain cAMP at
      relatively constant levels. Furthermore, the finding that Mg2+ATP-dependent
      adenylyl cyclase activity in wild-type cell extracts could be inhibited using
      anti-GNA-1 IgG suggests that GNA-1 directly interacts with adenylyl cyclase in N.
      crassa.

PMID- 10072320
TI  - Widespread distribution of low-copy-number variants of mitochondrial plasmid pEM
      in the genus Agaricus.
AB  - The incidence of the linear mitochondrial plasmid pEM in Agaricus spp. was
      believed to be rare, based on visualization by gel electrophoresis and Southern
      hybridization. However, we report in this study PCR amplification of pEM-like
      sequences from all but one species of Agaricus examined. Regions amplified
      included (1) the pEM RNA polymerase gene and (2) adjoining carboxy-termini of the
      DNA and RNA polymerase genes. Sequence data from the RNA polymerase-like products
      support a plasmid, rather than mitochondrial, origin for these sequences.
      Sequence variation was low, and most differences were silent or conservative at
      the amino acid level. Stop codons were found in two of seven sequence types
      suggesting that functional constraints are low. A parsimony-derived phylogeny for
      these sequences did not match expected phylogenies for the host species. Recent
      acquisition of the plasmid is presented as the most likely hypothesis explaining
      these observations.

PMID- 10072321
TI  - Pyruvate decarboxylase filaments are associated with the cortical cytoskeleton of
      asci and spores over the sexual cycle of filamentous ascomycetes.
AB  - We show that pyruvate decarboxylase (PDC) 8- to 10-nm-diameter filaments, first
      described in vegetative cells of Neurospora crassa, are ubiquitously present in
      filamentous fungi. The cellular arrangement of these structures was examined over
      the entire sexual cycle of the ascomycetes N. crassa, N. tetraesperma, Podospora
      anserina, and Sordaria macrospora. PDC-filaments were found associated with the
      cortical microtubule array of asci and ascospores and absent from the vicinity of
      spindles and spindle pole bodies. Nocodazole-induced depolymerization of the
      cortical microtubules results in the loss of PDC-filaments. Moreover, a S.
      macrospora mutant defective in cortical MT distribution shows abnormal PDC
      organization. Neurospora asci generated on various metabolic conditions, which
      modify the presence and relative abundance of PDC-filaments in vegetative cells,
      have identical patterns of subcellular distribution of these structures. A N.
      crassa mutant (snowflake) that accumulates giant bundles of PDC-filaments during
      vegetative growth, shows normal distribution of the filaments during ascogenesis.
      Thus, the regulation conditioning the presence and supramolecular assembly of PDC
      filaments in Neurospora differs between vegetative and sexual cells. Taken
      together, these results suggest that PDC in filamentous fungi may perform two
      functions, intervening as an enzyme in vegetative metabolism and as a structural
      protein associated with the cytoskeleton during sexual development.

PMID- 10072322
TI  - The expression and distribution of dense granule proteins in the enteric
      (Coccidian) forms of Toxoplasma gondii in the small intestine of the cat.
AB  - The expression and distribution of dense granule proteins in the enteric
      (coccidian) forms of Toxoplasma gondii in the small intestine of the cat.
      Experimental Parasitology 91, 203-211. The expression and location of the dense
      granule proteins (GRA1-6 and NTPase) in the merozoite and during asexual and
      sexual development of Toxoplasma gondii in the small intestine of the cat
      (definitive host) was examined by immuno-light and electron microscopy. This was
      compared with that of tachyzoites and bradyzoites present in the intermediate
      host. It was found that the merozoite contained the characteristic apical
      organelles plus a few large dense granules. By immunocytochemistry, dense
      granules in merozoites were negative for GRA proteins 1 to 6 in contrast to both
      tachyzoites and bradyzoites in which dense granules were positive for all six
      proteins. The GRA proteins were associated with the parasitophorous vacuole (PV)
      during tachyzoite and bradyzoite development but were absent from the PV of the
      enteric stages. However, the merozoite dense granules were positive for NTPase,
      which was similar to the tachyzoite while this antigen was down regulated in the
      bradyzoite. The apparent release of the NTPases into the PV formed by merozoites
      was also similar to that described for the tachyzoite, possibly reflecting the
      relative metabolic activity of the various stages. This study shows that the
      majority of GRA proteins have a similar stage-specific expression, which is
      independent of NTPases expression. These observations are consistent with T.
      gondii having a different host parasite relationship in the enteric forms, which
      does not involve the GRA proteins 1-6.

PMID- 10072323
TI  - Functional and quantitative analysis of splenic T cell immune responses following
      oral toxoplasma gondii infection in mice.
AB  - Functional and quantitative analysis of splenic T cell immune responses following
      oral Toxoplasma gondii infection in mice. Experimental Parasitology 91, 212-221.
      Immunity to Toxoplasma gondii is mediated primarily by the host T cell response.
      Although there is considerable information regarding host immunity following
      intraperitoneal infection with tachyzoites, little information is available
      regarding naturally acquired infection following peroral infection with
      bradyzoites. In this study, a sequential quantitative analysis of the cell
      mediated immune response was performed at the single cell level. To assess the
      kinetics of this response and parasitic loads, inbred mice were orally infected
      with the 76K strain bradyzoites of T. gondii. Within 24 h of infection,
      follicular hyperplasia followed by infiltration with histiocytes, macrophages,
      and apoptotic bodies was observed in the spleens of infected mice. T. gondii were
      detected from day 1, and counts increased gradually during the experimental
      period. Splenocyte DNA synthesis to antigen and mitogen was severely suppressed
      at days 7 and 10. The percentages of NK1.1(+) or delta gamma T cells were
      increased from day 1, whereas CD4(+) and CD8alpha+ T cells were signficantly
      increased after day 7 postinfection. CD25 expression and intracellular IFN-gamma
      production increased in NK1.1(+) cells on day 1 and by all other T cell subsets
      after day 4. Intracellular IL-4 did not increase until day 7, and IL-10
      production was increased in all T cell subsets after day 4. Together, these
      findings indicate that oral infection with T. gondii stimulates a strong cellular
      immune response that appears to polarize toward an early Th1 response. However,
      within 7 days, a strong immune Th2 regulatory response as well as high parasitic
      loads can be observed, with a reduction in lymphoproliferation to mitogen
      stimulation, increased production of IL-4 and IL-10, and evidence of T cell
      apoptosis in the splenic immune compartment.

PMID- 10072324
TI  - Trypanosoma brucei: cis-acting sequences involved in the developmental regulation
      of PARP expression.
AB  - The procyclic acidic repetitive protein (PARP or procyclin) of the parasitic
      protozoan Trypanosoma brucei is a developmentally regulated protein that shows
      extreme differences in its level of expression in different stages of the
      parasite's life cycle. Specifically, it is the major surface protein in the
      procyclic (insect) stage and, although the PARP gene is being actively
      transcribed in the mammalian bloodstream stage, there is no detectable PARP mRNA
      or protein in these cells. The 3'-untranslated region (UTR) of PARP, as well as
      other trypanosome genes, has the ability to confer the appropriate developmental
      regulation pattern onto chimeric reporter genes. To understand the mechanism of
      posttranscriptional regulation, selective replacement mutagenesis of the PARP
      mRNA 3'UTR was done to identify the cis-acting sequences involved in the down
      regulation of this mRNA in bloodstream-form T. brucei. Transient transformation
      of constructs containing the PARP promoter and 5'UTR, the beta-glucuronidase
      coding region, and the selectively mutagenized or unaltered PARP 3'UTR were
      performed in procyclic and bloodstream T. brucei. The results of the reporter
      gene assays on the transformed cells indicate that there are at least two
      elements in the PARP 3'UTR which in bloodstream cells are involved in regulation
      of PARP expression and which appear to function as negative elements. In
      procyclic cells, there are two regions in which mutagenesis indicates positive
      cis-regulatory sequences, one of which has been previously defined (A. Hehl et
      al., 1994, Proc. Natl. Acad. Sci. USA 91, 370-374). These results indicate that
      multiple cis-acting elements within the PARP 3'UTR are involved in the
      developmental regulation of PARP expression and that regulation is controlled in
      a complex manner, presumably involving several cellular trans-acting factors.

PMID- 10072325
TI  - Toxoplasma gondii: role of the phosphatidylcholine-specific phospholipase C
      during cell invasion and intracellular development.
AB  - The effect of D609, a specific inhibitor of phosphatidylcholine-specific
      phospholipase C, was investigated on cyst development of the Prugniaud strain of
      Toxoplasma gondii in vitro. Following treatment with the inhibitor 24 h after
      cell infection, cyst development was affected as assessed by staining with the
      bradyzoite-specific mAb CC2: the CC2-reactive antigen was shown to be differently
      located (in the wall versus the matrix under control conditions). This correlated
      with a decrease in parasite multiplication induced by D609. Pretreatment of the
      parasites with D609 inhibited their entry into the host cells, whereas
      pretreatment of the host cells enhanced the intracellular multiplication of the
      para sites, without any effect on cell invasion or cyst formation. Our results
      suggest a crucial role for phosphatidylcholine-specific phospholipase C in the
      pathophysiology of toxoplasmosis.

PMID- 10072326
TI  - Plasmodium vivax, P. cynomolgi, and P. knowlesi: identification of homologue
      proteins associated with the surface of merozoites.
AB  - We have identified a Plasmodium vivax merozoite surface protein (MSP) that
      migrates on SDS-polyacrylamide gels at a Mr of about 185 kDa. This protein was
      recognized by a P. vivax monoclonal antibody (mAb) that localizes the protein by
      immunofluorescence to the surface of merozoites and also immunoprecipitates this
      protein from NP-40 detergent extracts of [35S]methionine metabolically
      radiolabeled P. vivax schizonts. The P. vivax MSP does not become
      biosynthetically radiolabeled with [3H]glucoamine, [3H]myristate, [3H]palmitate,
      or [3H]mannose, indicating that this P. vivax MSP is not posttranslationally
      modified and bound to the merozoite membrane by a glycosylphosphatidylinositol
      (GPI) lipid anchor. Thus, in this respect, this protein is different from members
      of the MSP-1 protein family and from MSP-2 and MSP-4 of P. falciparum. The mAb
      cross-reacts with and outlines the surface of P. cynomolgi merozoites and
      immunoprecipitates a 150-kDa P. cynomolgi homologue. The mAb was used as an
      affinity reagent to purify the native homologous MSP from NP-40 extracts of P.
      cynomolgi mature schizonts in order to develop a specific polyclonal antiserum.
      The resulting anti-PcyMSP rabbit antiserum cross-reacts strongly with the P.
      vivax 185-kDa MSP and also recognizes an analogous 110-kDa protein from P.
      knowlesi. We have determined via an immunodepletion experiment that the 110-kDa
      P. knowlesi MSP corresponds to the PK 110 protein partially characterized earlier
      (Perler et al. 1987). The potential of P. vivax MSP as a vaccine candidate was
      addressed by conducting in vitro inhibition of erythrocyte invasion assays, and
      the IgG fraction of both the P. vivax MSP mAb and the P. cynomolgi MSP rabbit
      antiserum significantly inhibited entry of P. vivax merozoites. We denote, on a
      preliminary basis, these antigenically related merozite surface proteins PvMSP
      185, PcyMSP-150, and PkMSP-110.

PMID- 10072327
TI  - Haemonchus contortus: sequence heterogeneity of internucleotide binding domains
      from P-glycoproteins.
AB  - P-Glycoproteins are transmembrane proteins associated with acquired multidrug
      resistance in mammalian cells and some protozoan parasites by a process of active
      drug export. P-glycoproteins contain two nucleotide binding domains which couple
      ATP to the drug transport process. The region between the nucleotide binding
      domains of P-glycoproteins, termed the internucleotide binding domain (IBD), was
      PCR-amplified from adult and larval cDNA libraries using degenerate primers. The
      11 clones isolated by this method fall into several distinct groups, with one
      group of alleles displaying between 82 and 99% identity at the nucleotide level.
      This sets a baseline for sequence variation of transcribed alleles from a
      parasitic nematode. Northern blotting showed that P-glycoprotein genes are
      transcribed in a developmentally regulated fashion in Haemonchus contortus.
      Southern blots of H. contortus drug-resistant isolates with an IBD probe revealed
      a pattern consistent with the involvement of P-glycoprotein in resistance to
      avermectin/milbemycin anthelmintics.

PMID- 10072328
TI  - Plasmodium falciparum: structural and functional domains of the mature-parasite
      infected erythrocyte surface antigen.
AB  - The mature parasite-infected erythrocyte surface antigen (MESA) is a protein
      exported to the membrane skeleton of the infected red cell, where it forms a
      strong noncovalent interaction with the host red cell protein, protein 4.1. The
      complete gene structure of MESA from the Ugandan isolate Palo Alto is described.
      Comparison to the previously reported MESA sequence from the Papua New Guinean
      cloned line D10 reveals strong conservation of the general gene structure of a
      short first exon and a long second exon. The exact exon/intron boundaries were
      determined by the generation and sequencing of a cDNA from this region. The MESA
      gene from both isolates consists of seven blocks of repeats that are identical in
      order. Repeat blocks are conserved to a high degree; however, differences are
      noted in most blocks in the form of scattered mutations or differences in repeat
      numbers. Previous work had shown that synthetic peptides spanning a 19-residue
      region could inhibit the binding of MESA to protein 4.1. Removal of this region
      from MESA almost completely abolished the binding of MESA to IOVs. Sequencing of
      this region from a number of laboratory and field isolates demonstrates complete
      conservation of the cytoskeletal binding domain and flanking sequences.

PMID- 10072329
TI  - Trypanosomatidae: Phytomonas detection in plants and phytophagous insects by PCR
      amplification of a genus-specific sequence of the spliced leader gene.
AB  - In this paper we describe a method for the detection of Phytomonas spp. from
      plants and phytophagous insects using the PCR technique by targeting a genus
      specific sequence of the spliced leader (SL) gene. PCR amplification of DNA from
      48 plant and insect isolates previously classified as Phytomonas by
      morphological, biochemical, and molecular criteria resulted in all cases in a 100
      bp fragment that hybridized with the Phytomonas-specific spliced leader-derived
      probe SL3'. Moreover, this Phytomonas-specific PCR could also detect Phytomonas
      spp. in crude preparations of naturally infected plants and insects. This method
      shows no reaction with any other trypanosomatid genera or with plant and insect
      host DNA, revealing it to be able to detect Phytomonas spp. from fruit, latex, or
      phloem of various host plants as well as from salivary glands and digestive tubes
      of several species of insect hosts. Results demonstrated that SLPCR is a simple,
      fast, specific, and sensitive method that can be applied to the diagnosis of
      Phytomonas among cultured trypanosomatids and directly in plants and putative
      vector insects. Therefore, the method was shown to be a very specific and
      sensitive tool for diagnosis of Phytomonas without the need for isolation,
      culture, and DNA extraction of flagellates, a feature that is very convenient for
      practical and epidemiological purposes.

PMID- 10072331
TI  - Giardia muris: evidence for a beta-giardin homologue.

PMID- 10072330
TI  - Schistosoma mansoni: cloning and characterization of the Ras homologue.

PMID- 10072333
TI  - Formaldehyde allergy: A follow-up study.
AB  - BACKGROUND: Formaldehyde is a commonly used preservative in cosmetic products,
      cleaning agents and industrial products, and sensitization to formaldehyde
      frequently occurs. OBJECTIVE: The aim of the study was to evaluate the effect of
      extensive information and exposure assessment of formaldehyde on the prognosis of
      eczema. METHODS: The present study was designed as a clinical follow-up study of
      formaldehyde-sensitive patients. 105 patients diagnosed as formaldehyde allergic
      in the period January 1 1990 to December 31 1994 were thoroughly informed about
      their allergy, and exposure assessment was performed as a formaldehyde analysis
      on the patients' products. RESULTS: At follow-up 1 to 5 years later, 57 patients
      accepted the invitation to attend the outpatient clinic for an interview and a
      skin examination by a dermatologist, and were also at this time asked to bring
      products to which they were currently exposed for formaldehyde analysis.
      Evaluated by reported number of eczema eruptions and from objective skin
      examination patients had generally improved from their first visit to the
      department. At follow-up, 38 of 49 patients bringing products for analysis were
      still exposed to formaldehyde, as assessed by formaldehyde analysis on their
      products. There was a trend that severe eczema was found more often in patients
      still exposed to formaldehyde, but this finding was not statistically
      significant. Thirty-seven patients reported that they "paid attention to their
      allergy" when buying and using cosmetics or consumer products. CONCLUSION:
      Patients who paid attention to their allergy had statistically significantly
      fewer eruptions than those who did not.

PMID- 10072334
TI  - Epidemiological survey of contact dermatitis in Italy (1984-1993) by GIRDCA
      (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali).
AB  - BACKGROUND: The Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali
      (GIRDCA) resolved to obtain the most relevant data regarding contact dermatitis
      (CD) in Italy by means of a multicenter epidemiological study, involving research
      units (RU) throughout the country. The survey was performed with the
      collaboration of Generale Per l'Informatica, Rome (GEPIN) over the periods 1984
      to 1988 and 1989 to 1993. The analytical study (of a transverse kind) was aimed
      at supplying prevalence measures. MATERIALS AND METHODS: The number of subjects
      taking part in the survey was 42,839. All patients underwent patch testing with
      the GIRDCA standard series and were included in the survey only if the final
      diagnosis was either CD or eczematous dermatitis caused by contact. The main
      anamnestic, clinical data, and allergological test results of all patients were
      codified into a chart, and subsequently transcribed into a data bank. The data
      were then processed cumulatively and were statistically analysed by a chi-square
      for trend test. RESULTS: The four most frequent diagnoses (which, when considered
      together, make up 39,496 cases, or about 92% of all cases) proved to be
      nonoccupational allergic contact dermatitis (ACD), nonoccupational irritant
      contact dermatitis (ICD), occupational ACD, and occupational ICD. The haptens
      most frequently causing positive reactions in the total number of cases over the
      first 5 years were, in order of frequency: nickel sulphate, potassium dichromate,
      cobalt chloride, fragrance mix, balsam of Peru, and, in the second 5-year period,
      nickel sulphate, cobalt chloride, potassium dichromate, fragrance mix, and
      thimerosal. Occupational CD (ACD and ICD) was present in 11,694 cases overall,
      corresponding to approximately 27% of the total number of cases examined, and
      approximately 29% of all CD (including forms of nonoccupational CD). Regarding
      distribution by sex, a substantial equivalence of males and females for ACD, and
      a prevalence of females with ICD can be observed. Five occupations were reputed
      to be responsible for over 60% of total cases of occupational CD (housewives,
      bricklayers, workers in the metallurgic and mechanical industries, hairdressers,
      and healthcare personnel). Regarding the pathogenesis, a clearly dominant
      percentage of ACD may be observed among bricklayers and hairdressers, and of ICD
      among housewives. The haptens most frequently noted over the entire decade as the
      cause of positive reaction in occupational ACD were, in order of frequency,
      potassium dichromate, nickel sulphate, cobalt chloride, p-phenylenediamine and
      thiuram mix. Nonoccupational CD (ACD and ICD) was present in 27,802 cases
      overall, corresponding to about 65% of all cases under examination and over 70%
      of all CD (also including forms of occupational CD). In regard to distribution by
      sex, a clear dominance of females, as opposed to males, can be noted for ACD and
      also (although to a lesser extent) for ICD. The main products and materials (ie,
      components and relative substances) that are pinpointed as being responsible for
      nonoccupational ACD, were, in order of frequency, clothing accessories,
      cosmetics, topical pharmaceuticals, and clothing. The haptens most frequently
      recognized as the cause of positive reactions were, in order of frequency, nickel
      sulphate, fragrance mix, cobalt chloride, balsam of Peru, potassium dichromate,
      ethylenediamine, and diaminodiphenylmethane.

PMID- 10072335
TI  - Demonstration of the contact sensitizer p-tert-butylcatechol in p-tert
      butylphenol formaldehyde resin.
AB  - BACKGROUND: In regard to patients hypersensitive to p-tert-butylphenol
      formaldehyde resin (PTBP-F-R), it is for diagnostic, therapeutic, and preventive
      reasons necessary to know the identity of the primary sensitizing substances and
      their sensitizing capacities, as well as their cross-reaction patterns. In
      patients hypersensitive to PTBP-F-R, we have demonstrated a statistically
      significant overrepresentation of simultaneous reactions to p-tert-butylcatechol
      (PTBC). In the guinea pig, we have shown that PTBC is a strong sensitizer, giving
      cross reactions to p-tert-butylphenol. Furthermore, PTBC cross reacts to the PTBP
      F-R monomer 2,6-methylol p-tert-butylphenol, which is a strong sensitizer in the
      guinea pig. OBJECTIVE: The aim of this study was to investigate the background to
      the observed simultaneous reactions to PTBP-F-R and PTBC and to see if these
      could be explained by the presence of PTBC in PTBP-F-R. METHODS: High pressure
      liquid chromatography (HPLC), nuclear magnetic resonance spectrometry (NMR), mass
      spectrometry (MS). RESULTS: PTBC was isolated and identified; the concentrations
      in two resins were determined. HPLC analyses showed the presence of 0.099% and
      0.020% wt/wt PTBC, respectively. CONCLUSION: This study shows that PTBC can be
      present in at least in some brands of PTBP-F-R. The study also indicates that a
      positive patch test reaction to PTBP-F-R could be an indication of allergy to
      PTBC, at least in patients with high sensitivity to PTBC. When detecting contact
      allergies to PTBP-F-R in a patient for whom no clinically relevant exposure to
      this resin can be found, the possibility of PTBC as the eliciting factor should
      be considered.

PMID- 10072336
TI  - The benefit of patch testing with a corticosteroid at a low concentration.
AB  - BACKGROUND: Patch testing with corticosteroid marker molecules is advocated
      because testing with all available corticosteroids is impossible in clinical
      practice. Most commonly used are budesonide, tixocortol pivalate, and
      hydrocortisone-17-butyrate. We have been patch testing not only with the three
      markers, but also with two corticosteroid mixes, each consisting of different
      concentrations of the three markers. OBJECTIVE: We describe a patient allergic to
      tixocortol pivalate, who was diagnosed by using a lower patch test concentration
      that recommended, 0.1% in petrolatum, as well as a weak corticosteroid mix,
      0.202%. METHODS: The patient was patch tested to a standard series, including the
      two corticosteroid mixes and its three constituents. RESULTS: None of the
      corticosteroid preparations were positive on the first ordinary reading day, day
      3, whereas both tixocortol pivalate at 0.1% and the corticosteriod mix at 0.202%
      were positive on the second ordinary reading day, day 7, whereas all tested
      corticosteroids in the standard series gave positive reactions on d10.
      CONCLUSION: The possible benefit of patch testing with a corticosteroid at a low
      concentration is supported, as is the significance of late readings beyond D4.

PMID- 10072337
TI  - Onycholysis from nail lacquer: a complication of nail enhancement?

PMID- 10072338
TI  - Garlic-related dermatoses: case report and review of the literature.
AB  - BACKGROUND: Garlic is widely appreciated as a spice and as a vegetable as well as
      an over-the-counter phytotherapeutic. From a dermato-allergological standpoint,
      several garlic-related adverse reactions have to be distinguished. OBJECTIVE: The
      corresponding literature is reviewed briefly, with regard to our present
      observation of a cook, who contracted garlic-induced contact dermatitis being
      analyzed for its complex pathomechanism. METHODS: The patient showed a positive
      type-IV patch test reaction for diallyl disulfide, a low molecular weight garlic
      ingredient; and strong, non-irritant reactions after 20 min and 24 hrs in the
      scratch chamber test with fresh total garlic. RESULTS: Thus, in this case of an
      occupational dermatosis, protein contact dermatitis had to be considered, as well
      as allergic type-IV contact dermatitis as a co-existing pathomechanism.
      CONCLUSIONS: The spectrum of garlic-related adverse reactions comprises irritant
      contact dermatitis, with the rare variant of zosteriform dermatitis; induction of
      pemphigus, allergic asthma and rhinitis; contact urticaria; protein contact
      dermatitis; allergic contact dermatitis, including the hematogenic variant; as
      well as combinations thereof, as evidenced by our present case observation.

PMID- 10072339
TI  - Facial dermatitis, contact urticaria, rhinoconjunctivitis, and asthma induced by
      potato.
AB  - BACKGROUND: Potato contains multiple heat-labile proteins which can induce
      immediate hypersensitivity reactions. Rhino-conjunctivitis, asthma, contact
      urticaria and protein contact dermatitis have been described in association with
      potato exposure. OBJECTIVE: A patient with possible airborne facial dermatitis to
      potato is described. RESULTS: A middle-aged atopic housewife with pre-existent
      atopic dermatitis suffered from rhino-conjunctivitis, asthma, and contact
      urticaria when pealing raw potatoes, but her main complaint was intense,
      treatment-resistant dermatitis of the face. The investigations showed a positive
      prick test, a positive patch test, and positive specific serum IgE to raw potato.
      Potato avoidance led not only to the resolution of the immediate symptoms, but
      also of the facial dermatitis, suggesting she had dermatitis due to this
      vegetable. CONCLUSIONS: Potato may induce contact dermatitis with positive
      immediate and delayed hypersensitivity tests.

PMID- 10072340
TI  - Perianal contact dermatitis caused by nail lacquer allergy.
AB  - BACKGROUND: Allergy to nail cosmetics is relatively infrequent compared with
      other cosmetics. Allergic contact dermatitis from nail lacquer typically affects
      the eyelids, cheeks, sides of the neck, hands and periungual areas, and less
      frequently another areas. OBJECTIVE: We report on a patient who developed nail
      lacquer-related allergic contact dermatitis in an infrequent location, namely the
      perianal area. METHODS: A patient with perianal and eyelid pruritus and
      dermatitis was patch tested with the TRUE tests, cosmetic series, personal
      cosmetics, plastic and glue series, and personal nail lacquers. RESULTS: A +2
      positive allergic response was observed at the sites of the toluenesulfonamide
      formaldehyde resin and at the sites the patient's nail lacquers at days 2 and 4.
      CONCLUSION: Nail lacquer allergy may be observed at distant sites, and the
      perianal area may be involved more frequently than was previously thought.

PMID- 10072341
TI  - The language of plants.
AB  - Precise identification of plants requires consistent use of a well-established
      binomial nomenclature. This review highlights the basis for the systematic method
      of naming plants, the importance of its use, and the reasons for nomenclature
      changes over time. Furthermore, it provides practical tips for the identification
      of specific plants in the course of managing patients with suspected plant
      induced contact dermatitis.

PMID- 10072343
TI  - The sensitization potential of methyl methacrylate and ethyl methacrylate.

PMID- 10072344
TI  - Acute dermatitis after contact with dicyclohexylcarbodiimide.

PMID- 10072345
TI  - Allergic contact dermatitis caused by sorbic acid: rare occurrence.

PMID- 10072348
TI  - Is the face and neck pattern of atopic dermatitis in Japan a special variant?
AB  - BACKGROUND: Adult atopic dermatitis (AD) with severe and refractory eruptions on
      the face, neck, and upper trunk, although quite rare in western countries, has
      increased in Japan. OBJECTIVE: We have tried to clarify the possible causative
      factors for this particular type of AD, predominantly seen in Japan. METHODS:
      Eighty-seven AD patients (37 men and 50 women) who had severe and refractory
      facial and neck lesions were patch tested with topical medicaments, cosmetics,
      and skin-management products. RESULTS: Thirty-seven (42. 5%) patients showed
      positive reactions to more than one of those products: 14 patients to shampoo,
      rinse, or soap; 11 to topical nonsteroidal anti-inflammatory agents (NSAIDs); 7
      to cosmetics; and 6 to corticosteroids. CONCLUSION: We believe that topical
      NSAIDs, (which are often prescribed for the treatment of AD in Japan and rarely
      used for the treatment of eczamatous skin disorders in western countries), as
      well as common detergents, play important roles in the increased prevalence of AD
      patients with severe and refractory lesions on the face, neck, and upper trunk in
      Japan.

PMID- 10072349
TI  - AP-1 transcription factors in yeast.
AB  - In the past two years, the completion of the Saccharomyces cerevisiae genome
      project and molecular analysis of other fungal species has resulted in the
      identification of a growing number of yeast AP-1 transcription factors.
      Characterisation of these factors indicates that, like their mammalian
      counterparts, they activate gene expression in response to a variety of
      extracellular stimuli. In particular, these factors are required for the response
      to oxidative stress and for surviving exposure to a variety of cytotoxic agents.
      Much progress has also been made in understanding how members of this family of
      proteins are regulated. These studies promise to further our awareness of
      eukaryotic stress responses and are likely to have implications for the study of
      mammalian AP-1.

PMID- 10072350
TI  - Histone acetylases and deacetylases in cell proliferation.
AB  - There are several enzymes, acetylases and deacetylases, that can regulate
      transcription by modifying the acetylation state of histones or other promoter
      bound transcription factors. Some of these enzymes are present in multisubunit
      complexes. Recent efforts to understand the biological role of these enzymes
      reveals their involvement in cell-cycle regulation and differentiation.
      Furthermore, accumulating evidence suggests that deregulation of acetylase and
      deacetylase activity plays a causative role in the generation of cancer.

PMID- 10072351
TI  - CDK inhibition and cancer therapy.
AB  - The cell-division cycle is a tightly controlled process that is regulated by the
      cyclin/CDK family of protein kinase complexes. Stringent control of this process
      is essential to ensure that DNA synthesis and subsequent mitotic division are
      accurately and coordinately executed. There is now strong evidence that CDKs,
      their regulators, and substrates are the targets of genetic alteration in many
      human cancers. As a result of this, the CDKs have been targeted for drug
      discovery and a number of small molecule inhibitors of CDKs have been identified.

PMID- 10072352
TI  - The oncogenic activation of beta-catenin.
AB  - The activation of beta-catenin to an oncogenic state can result from the
      inactivation of the tumor suppressor adenomatous polyposis coli (APC), by direct
      mutation in the beta-catenin gene, or by the activation of wnt receptors. Once
      activated, beta-catenin most likely promotes tumor progression through its
      persistent interaction with one or more of its numerous downstream targets.

PMID- 10072353
TI  - pRb and E2f-1 in mouse development and tumorigenesis.
AB  - Our understanding of how RB and E2F-1 function has progressed significantly from
      the model in which RB negatively regulates expression of genes required for S
      phase by binding to and inhibiting E2F-1. Both RB and E2F-1 have been shown
      recently to possess additional properties and mechanisms of regulation relevant
      to developmental and tumorigenic processes. In particular, it is now realised
      that RB has E2F-independent tumor suppressor functions which rely upon the
      ability of RB to induce differentiation. For its part, E2F-1 is unique amongst
      E2F family members in its capacity to induce apoptosis and this function is
      clearly relevant to our appreciation of E2F-1 as a conditional tumor suppressor.
      E2F-1 can induce both apoptosis and S-phase transition and whether E2F-1 acts as
      an oncogene or a tumor-suppressor gene may depend on the extent to which E2F-1
      induces apoptosis as opposed to G1/S transition.

PMID- 10072354
TI  - Eukaryotic DNA mismatch repair.
AB  - Eukaryotic mismatch repair (MMR) has been shown to require two different
      heterodimeric complexes of MutS-related proteins: MSH2-MSH3 and MSH2-MSH6. These
      two complexes have different mispair recognition properties and different
      abilities to support MMR. Alternative models have been proposed for how these MSH
      complexes function in MMR. Two different heterodimeric complexes of MutL-related
      proteins, MLH1-PMS1 (human PMS2) and MLH1-MLH3 (human PMS1) also function in MMR
      and appear to interact with other MMR proteins including the MSH complexes and
      replication factors. A number of other proteins have been implicated in MMR,
      including DNA polymerase delta, RPA (replication protein A), PCNA (proliferating
      cell nuclear antigen), RFC (replication factor C), Exonuclease 1, FEN1 (RAD27)
      and the DNA polymerase delta and epsilon associated exonucleases. MMR proteins
      have also been shown to function in other types of repair and recombination that
      appear distinct from MMR. MMR proteins function in these processes in conjunction
      with components of nucleotide excision repair (NER) and, possibly, recombination.

PMID- 10072355
TI  - Ras caught in another affair: the exchange factors for Ral.
AB  - The Ral guanine nucleotide exchange factors are direct targets of Ras, providing
      a mechanism for Ral activation by extracellular signals. In addition, Ral can be
      activated by a Ras-independent pathway. Ral guanine nucleotide exchange factors
      contribute to cellular transformation induced by oncogenic Ras through an Erk
      independent mechanism which may involve activation of transcription.

PMID- 10072356
TI  - The INK4A/ARF locus and its two gene products.
AB  - The INK4A/ARF locus on chromosome 9 is one of the sites mutated most frequently
      in human cancer. Two genes comprising overlapping reading frames encoding
      p16(INK4a) and p19(ARF) have been discovered at this locus and, remarkably, both
      play an important role in regulating cell growth, survival and senescence.

PMID- 10072357
TI  - Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and
      degradation.
AB  - Mitogenic and nutritional signals must be integrated for a cell to grow. The
      target of rapamycin (TOR) is emerging as an effector for signals which indicate
      to the cell whether the external environment is conducive for growth. Use of the
      immunosuppressant rapamycin, a bacterial macrolide, has been instructive in
      identifying potential signaling components downstream of TOR, leading to the
      observation that both protein synthesis and turnover are under TOR control. The
      central issues concerning TOR are the identification of the proliferative and
      anti-proliferative signals which mediate its function and the mechanisms by which
      these signals are transduced to downstream molecules.

PMID- 10072359
TI  - The spindle checkpoint.
AB  - Prior to sister-chromatid separation, the spindle checkpoint inhibits cell-cycle
      progression in response to a signal generated by mitotic spindle damage or by
      chromosomes that have not attached to microtubules. Recent work has shown that
      the spindle checkpoint inhibits cell-cycle progression by direct binding of
      components of the spindle checkpoint pathway to components of a specialized
      ubiquitin-conjugating system that is responsible for triggering sister-chromatid
      separation.

PMID- 10072358
TI  - Telomere maintenance mechanisms and cellular immortalization.
AB  - Immortal cell populations are able to proliferate indefinitely. Immortalization
      is associated with activation of processes that compensate for the telomeric
      shortening that accompanies cell division in normal somatic cells. In many
      immortal cell lines, telomere maintenance is provided by the action of the
      ribonucleoprotein enzyme complex, telomerase. Some immortal cell lines have
      undetectable or very low levels of telomerase activity and there is evidence that
      these cells maintain their telomeres by an alternative mechanism.

PMID- 10072360
TI  - Coordination of cell growth with cell division.
AB  - Proliferating cells must increase their mass coordinately with cell division.
      Recent evidence suggests that coupling of cell growth with cell division might be
      achieved by making synthesis of activators of cell division particularly
      sensitive to the capacity of the cell's protein synthesis machinery.

PMID- 10072361
TI  - The regulation of replication origin activation.
AB  - At the start of the cell-division programme, proteins must be assembled onto
      replication origins to establish competence for initiation of DNA synthesis. At
      the correct moment, other effectors must then coordinate appropriate firing of
      the various origins to control entry into and progress through S phase. These
      processes are key targets of cell-cycle control, and understanding their
      regulation will provide a deeper knowledge of the mechanisms controlling cell
      proliferation.

PMID- 10072362
TI  - Establishing links between developmental signaling pathways and cell-cycle
      regulation in Drosophila.
AB  - During development, cell signaling often mediates the choice of cell fate and the
      accompanying cell biological events that dictate morphogenesis - such as progress
      through the cell division cycle. Recent genetic analyses in Drosophila are
      beginning to reveal the molecular connections between developmental signaling
      pathways and key regulators of the cell cycle.

PMID- 10072363
TI  - Transcriptional control of neurotransmitter phenotype.
AB  - The specification of neurotransmitter phenotype is an important aspect of
      neuronal fate determination. Recent studies have begun to define essential
      transcriptional regulators involved in controlling the mode of neurotransmission
      in vertebrates and invertebrates, and to examine their regulation by cell
      extrinsic factors. An emerging concept is that the control of transmitter choice
      is intimately linked to that of other aspects of the neuronal phenotype.

PMID- 10072364
TI  - Sensitive periods and circuits for learned birdsong.
AB  - Experience influences the development of certain behaviors and their associated
      neural circuits during a discrete period after birth. Songbirds, with their
      highly quantifiable vocal output and well-delineated vocal control circuitry,
      provide an excellent context in which to examine the neural mechanisms regulating
      sensitive periods for learning. Recent discoveries indicate that auditory input
      to the vocal control circuitry in songbirds is dynamically modulated and show
      that neural circuitry previously thought to be used only in plastic juvenile song
      may also actively maintain stable adult song. These findings provide important
      clues to how sensitive periods for auditory feedback and vocal plasticity are
      regulated during song development.

PMID- 10072365
TI  - Control of muscle fibre and motoneuron diversification.
AB  - Recent studies have elucidated both the mechanism of early formation of diverse
      muscle fibre types and the matching of diverse populations of motoneurons to
      their appropriate muscle targets. Highlights include the demonstration that
      distinct signals are necessary for the formation of several distinct myoblast
      populations in the vertebrate somite, the identification of motoneuron subtypes,
      studies of how motoneurons target appropriate muscles, and rapid progress on the
      Drosophila neuromuscular system. We propose a model in which four classes of
      decision control the patterning of both motoneurons and muscles.

PMID- 10072366
TI  - The origin of spontaneous activity in developing networks of the vertebrate
      nervous system.
AB  - Spontaneous neuronal activity has been detected in many parts of the developing
      vertebrate nervous system. Recent studies suggest that this activity depends on
      properties that are probably shared by all developing networks. Of particular
      importance is the high excitability of recurrently connected, developing networks
      and the presence of activity-induced transient depression of network
      excitability. In the spinal cord, it has been proposed that the interaction of
      these properties gives rise to spontaneous, periodic activity.

PMID- 10072367
TI  - Formation of lamina-specific synaptic connections.
AB  - In many parts of the vertebrate central nervous system, inputs of distinct types
      confine their synapses to individual laminae. Such laminar specificity is a major
      determinant of synaptic specificity. Recent studies of several laminated
      structures have begun to identify some of the cells (such as guidepost neurons in
      hippocampus), molecules (such as N-cadherin in optic tectum, semaphorin/collapsin
      in spinal cord, and ephrins in cerebral cortex), and mechanisms (such as activity
      dependent refinement in lateral geniculate) that combine to generate laminar
      specificity.

PMID- 10072368
TI  - Neurotrophin regulation of synaptic transmission.
AB  - Examples of signaling molecules that are devoted to neuronal development at the
      exclusion of other functions are scarce. It may then come as no surprise to learn
      that a family of molecules that promote neuronal survival, differentiation and
      outgrowth also regulate synaptic transmission at both developing and mature
      synapses. Indeed, many studies over the past five years have shown that
      neurotrophins, including nerve growth factor (NGF), neurotrophin-3 (NT-3), NT-4/5
      and brain-derived neurotrophic factor (BDNF), have both rapid and long-latency
      influences on synaptic strength. New research has highlighted the enormous range
      of neurotrophin actions at both developing and mature synapses, demonstrating
      that transmission can be enhanced or reduced at excitatory and inhibitory
      synapses by either pre- or postsynaptic mechanisms.

PMID- 10072369
TI  - Neuronal activity during development: permissive or instructive?
AB  - Experimental studies over the past year have shown that neural activity has a
      range of effects on the development of neural pathways. Although activity appears
      unimportant for establishing many aspects of the gross morphology and topology of
      the brain, there are many cases where the presence of neural activity is
      essential for the formation of a mature system of neural connections; in some
      instances, the pattern of neural activity actually orchestrates the final
      arrangement of neural connections.

PMID- 10072370
TI  - Stem cells in the adult mammalian central nervous system.
AB  - Over the past year, evidence has accrued that adult CNS stem cells are a
      widespread progenitor cell type. These cells may normally replace neurons and/or
      glia in the adult brain and spinal cord. Advances have been made in understanding
      the signals that regulate stem cell proliferation and differentiation. A deeper
      understanding of the structure of germinal zones has helped us move towards
      identifying stem cells in vivo. Recent studies suggest that the fate of stem cell
      progeny in vivo may be linked to the complexity of the animal's environment.

PMID- 10072371
TI  - Gene regulation by patterned electrical activity during neural and skeletal
      muscle development.
AB  - Patterned neural activity modifies central synapses during development and the
      physiological properties of skeletal muscle by selectively repressing or
      stimulating transcription of distinct genes. The effects of neural activity are
      mostly mediated by calcium. Of particular interest are the cellular mechanisms
      that may be used to sense and convert changes in calcium into specific
      alterations in gene expression. Recent studies have addressed the importance of
      spatial heterogeneity or of temporal changes in calcium levels for the regulation
      of gene expression.

PMID- 10072372
TI  - Maternal care and the development of stress responses.
AB  - Studies dating from the 1950s have documented the impact of early life events on
      the development of behavioral and endocrine responses to stress. Recent findings
      suggest that these effects are mediated through changes in mother-offspring
      interactions and have identified central corticotropin-releasing factor systems
      as a critical target for the effects of variations in maternal care.

PMID- 10072373
TI  - Development of the vertebrate main olfactory system.
AB  - Olfactory receptor neurons project from the sensory epithelium to stereotyped
      targets within the olfactory bulb. Recent studies suggest that the generation of
      this precise spatial map probably involves a hierarchy of guidance events, as
      receptor neurons integrate information present in the epithelium and bulb to
      reach their target.

PMID- 10072374
TI  - Control of neurogenesis--lessons from frogs, fish and flies.
AB  - Two types of genes activated by neural inducers have been identified, those that
      lead to the activation of proneural genes and those that limit the activity of
      these genes to specific domains in the neural plate. The analysis of these genes
      has begun to fill gaps in our understanding of events that lead from neural
      induction to the generation of neurons within three longitudinal columns in the
      Xenopus and zebrafish neural plate.

PMID- 10072375
TI  - Eph receptors and ephrins in neural development.
AB  - Ephrins, ligands for the Eph family of receptor tyrosine kinases, are pivotal
      players in many developmental phenomena in both the central and peripheral
      nervous systems. Ephrins appear to act typically, but not exclusively, as
      repellents throughout development to influence axon pathfinding and topographic
      mapping, as well as restricting cell migration and intermingling. Recent findings
      are beginning to characterize the function and signaling of ephrins, as well as
      major roles for them in other tissues.

PMID- 10072376
TI  - The roles of intrinsic and extrinsic cues and bHLH genes in the determination of
      retinal cell fates.
AB  - A fundamental issue concerning development of the vertebrate retina is the
      relative contributions of extrinsic and intrinsic cues to the determination of
      cell fate. Recent findings suggest that retinal progenitors go through a series
      of changes in intrinsic properties that control their competence to make
      different cell types and that extrinsic cues influence the ratios of the cell
      types that they produce. Recent studies of the role of the basic helix-loop-helix
      genes in retinal development have indicated that they can regulate competence
      and/or other aspects of cell fate determination.

PMID- 10072377
TI  - Specification of dopaminergic and serotonergic neurons in the vertebrate CNS.
AB  - The early specification of dopaminergic and serotonergic neurons during
      vertebrate CNS development relies on signals produced by a small number of
      organizing centers. Recent studies have characterized these early organizing
      centers, the manner in which they may be established, the inductive signals they
      produce, and candidate signaling systems that control the later development of
      the dopaminergic system.

PMID- 10072378
TI  - A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and
      Hedgehog signaling pathways.

PMID- 10072379
TI  - Gene targeting in the silkworm by use of a baculovirus.
AB  - The Bombyx mori fibroin light (L)-chain gene was cloned and the green fluorescent
      protein (GFP) gene inserted into exon 7. The chimeric L-chain-GFP gene was used
      to replace the polyhedrin gene of Autographa californica nucleopolyhedrovirus
      (AcNPV). This recombinant virus was used to target the L-chain-GFP gene to the L
      chain region of the silkworm genome. Female moths were infected with the
      recombinant virus and then mated with normal male moths. Genomic DNA from their
      progenies was screened for the desired targeting event. This analysis showed that
      the chimeric gene had integrated into the L-chain gene on the genome by
      homologous recombination and was stably transmitted through generations. The
      chimeric gene was expressed in the posterior silk gland, and the gene product was
      spun into the cocoon layer.

PMID- 10072380
TI  - Defects in Saccharomyces cerevisiae protein phosphatase type I activate the
      spindle/kinetochore checkpoint.
AB  - A conditional allele of type 1 protein phosphatase (glc7-129) in Saccharomyces
      cerevisiae causes first cycle arrest in G2/M, characterized by cells with a short
      spindle and high H1 kinase activity. Point-of-execution experiments indicate
      Glc7p function is required in G2/M just before anaphase for the completion of
      mitosis. Loss of the spindle/kinetochore checkpoint in glc7-129 cells abolishes
      the G2/M cell cycle arrest with a concomitant increase in chromosome loss and
      reduced viability. These results support a role for Glc7p in regulating
      kinetochore attachment to the spindle, an event monitored by the
      spindle/kinetochore checkpoint.

PMID- 10072381
TI  - Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male
      and female meiosis.
AB  - Members of the mammalian mismatch repair protein family of MutS and MutL homologs
      have been implicated in postreplicative mismatch correction and chromosome
      interactions during meiotic recombination. Here we demonstrate that mice carrying
      a disruption in MutS homolog Msh5 show a meiotic defect, leading to male and
      female sterility. Histological and cytological examination of prophase I stages
      in both sexes revealed an extended zygotene stage, characterized by impaired and
      aberrant chromosome synapsis, that was followed by apoptotic cell death. Thus,
      murine Msh5 promotes synapsis of homologous chromosomes in meiotic prophase I.

PMID- 10072382
TI  - The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores
      in budding yeast.
AB  - Chromosome segregation depends on kinetochores, the structures that mediate
      chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which
      encodes a protein kinase, in a screen for budding yeast mutants that have defects
      in sister chromatid separation and segregation. Cytological tests show that ipl1
      mutants can separate sister chromatids but are defective in chromosome
      segregation. Kinetochores assembled in extracts from ipl1 mutants show altered
      binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in
      vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p
      phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are
      regulated during the cell cycle. This pattern of localization and regulation is
      similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2
      protein. Because aurora2 has been implicated in oncogenesis, defects in
      kinetochore function may contribute to genetic instability in human tumors.

PMID- 10072383
TI  - Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase
      Glc7p.
AB  - We have investigated the role of protein phosphorylation in regulation of
      Saccharomyces cerevisiae kinetochores. By use of phosphatase inhibitors and a
      type 1 protein phosphatase mutant (glc7-10), we show that the microtubule binding
      activity, but not the centromeric DNA-binding activity, of the kinetochore
      complex is regulated by a balance between a protein kinase and the type 1 protein
      phosphatase (PP1) encoded by the GLC7 gene. glc7-10 mutant cells exhibit low
      kinetochore-microtubule binding activity in vitro and a high frequency of
      chromosome loss in vivo. Specifically, the Ndc10p component of the centromere DNA
      binding CBF3 complex is altered by the glc7-10 mutation; Ndc10p is
      hyperphosphorylated in glc7-10 extracts. Furthermore, addition of recombinant
      Ndc10p reconstitutes the microtubule-binding activity of a glc7-10 extract to
      wild-type levels. Finally, the glc7-10-induced mitotic arrest is abolished in
      spindle checkpoint mutants, suggesting that defects in kinetochore-microtubule
      interactions caused by hyperphosphorylation of kinetochore proteins activate the
      spindle checkpoint.

PMID- 10072384
TI  - Nuclear import of the Drosophila Rel protein Dorsal is regulated by
      phosphorylation.
AB  - In Drosophila, dorsal-ventral polarity is determined by a maternally encoded
      signal transduction pathway that culminates in the graded nuclear localization of
      the Rel protein, Dorsal. Dorsal is retained in the cytoplasm by the IkappaB
      protein, Cactus. Signal-dependent phosphorylation of Cactus results in the
      degradation of Cactus and the nuclear targeting of Dorsal. We present an in-depth
      study of the functional importance of Dorsal phosphorylation. We find that Dorsal
      is phosphorylated by the ventral signal while associated with Cactus, and that
      Dorsal phosphorylation is essential for its nuclear import. In vivo
      phospholabeling of Dorsal is limited to serine residues in both ovaries and early
      embryos. A protein bearing mutations in six conserved serines abolishes Dorsal
      activity, is constitutively cytoplasmic, and appears to eliminate Dorsal
      phosphorylation, but still interacts with Cactus. Two individual serine-to
      alanine mutations produce unexpected results. In a wild-type signaling
      background, a mutation in the highly conserved PKA site (S312) produces only a
      weak loss-of-function; however, it completely destabilizes the protein in a
      cactus mutant background. Significantly, the phosphorylation of another
      completely conserved serine (S317) regulates the high level of nuclear import
      found in ventral cells. We conclude that the formation of a wild-type Dorsal
      nuclear gradient requires the phosphorylation of both Cactus and Dorsal. The
      strong conservation of the serines suggests that phosphorylation of other Rel
      proteins is essential for their proper nuclear targeting.

PMID- 10072385
TI  - Interaction of the U1 snRNP with nonconserved intronic sequences affects 5'
      splice site selection.
AB  - Intron definition and splice site selection occur at an early stage during
      assembly of the spliceosome, the complex mediating pre-mRNA splicing. Association
      of U1 snRNP with the pre-mRNA is required for these early steps. We report here
      that the yeast U1 snRNP-specific protein Nam8p is a component of the commitment
      complexes, the first stable complexes assembled on pre-mRNA. In vitro and in
      vivo, Nam8p becomes indispensable for efficient 5' splice site recognition when
      this process is impaired as a result of the presence of noncanonical 5' splice
      sites or the absence of a cap structure. Nam8p stabilizes commitment complexes in
      the latter conditions. Consistent with this, Nam8p interacts with the pre-mRNA
      downstream of the 5' splice site, in a region of nonconserved sequence.
      Substitutions in this region affect splicing efficiency and alternative splice
      site choice in a Nam8p-dependent manner. Therefore, Nam8p is involved in a novel
      mechanism by which a snRNP component can affect splice site choice and regulate
      intron removal through its interaction with a nonconserved sequence. This
      supports a model where early 5' splice recognition results from a network of
      interactions established by the splicing machinery with various regions of the
      pre-mRNA.

PMID- 10072386
TI  - Identification of eight proteins that cross-link to pre-mRNA in the yeast
      commitment complex.
AB  - In the yeast commitment complex and the mammalian E complex, there is an
      important base-pairing interaction between the 5' end of U1 snRNA and the
      conserved 5' splice site region of pre-mRNA. But no protein contacts between
      splicing proteins and the pre-mRNA substrate have been defined in or near this
      region of early splicing complexes. To address this issue, we used 4-thiouridine
      substituted 5' splice site-containing RNAs as substrates and identified eight
      cross-linked proteins, all of which were identified previously as commitment
      complex components. The proteins were localized to three domains: the exon, the
      six nucleotides of the 5' ss region, and the downstream intron. The results
      indicate that the 5' splice site region and environs are dense with protein
      contacts in the commitment complex and suggest that some of them make important
      contributions to formation or stability of the U1 snRNP-pre-mRNA complex.

PMID- 10072387
TI  - Binding of hnRNP H to an exonic splicing silencer is involved in the regulation
      of alternative splicing of the rat beta-tropomyosin gene.
AB  - In the rat beta-tropomyosin (beta-TM) gene, exons 6 and 7 are spliced
      alternatively in a mutually exclusive manner. Exon 6 is included in mRNA encoding
      nonmuscle TM-1, whereas exon 7 is used in mRNA encoding skeletal muscle beta-TM.
      Previously, we demonstrated that a six nucleotide mutation at the 5' end of exon
      7, designated as ex-1, activated exon 7 splicing in nonmuscle cells. In this
      study, we show that the activating effect of this mutation is not the result of
      creating an exonic splicing enhancer (ESE) or disrupting a putative secondary
      structure. The sequence in exon 7 acts as a bona fide exonic splicing silencer
      (ESS), which is bound specifically by a trans-acting factor. Isolation and
      peptide sequencing reveal that this factor is hnRNP H, a member of the
      heterogeneous nuclear ribonucleoprotein (hnRNP) family. Binding of hnRNP H
      correlates with the ESS activity. Furthermore, addition of antibodies that
      specifically recognizes hnRNP H to the splicing reactions or partial depletion of
      hnRNP H from nuclear extract activates exon 7 splicing in vitro and this effect
      can be reversed by addition of purified recombinant hnRNP H. These results
      indicate that hnRNP H participates in exclusion of exon 7 in nonmuscle cells. The
      involvement of hnRNP H in the activity of an ESS may represent a prototype for
      the regulation of tissue- and developmental-specific alternative splicing.

PMID- 10072388
TI  - Control of cell cycle progression by c-Jun is p53 dependent.
AB  - The c-jun proto-oncogene encodes a component of the mitogen-inducible immediate
      early transcription factor AP-1 and has been implicated as a positive regulator
      of cell proliferation and G1-to-S-phase progression. Here we report that
      fibroblasts derived from c-jun-/- mouse fetuses exhibit a severe proliferation
      defect and undergo a prolonged crisis before spontaneous immortalization. The
      cyclin D1- and cyclin E-dependent kinases (CDKs) and transcription factor E2F are
      poorly activated, resulting in inefficient G1-to-S-phase progression.
      Furthermore, the absence of c-Jun results in elevated expression of the tumor
      suppressor gene p53 and its target gene, the CDK inhibitor p21, whereas
      overexpression of c-Jun represses p53 and p21 expression and accelerates cell
      proliferation. Surprisingly, protein stabilization, the common mechanism of p53
      regulation, is not involved in up-regulation of p53 in c-jun-/- fibroblasts.
      Rather, c-Jun regulates transcription of p53 negatively by direct binding to a
      variant AP-1 site in the p53 promoter. Importantly, deletion of p53 abrogates all
      defects of cells lacking c-Jun in cell cycle progression, proliferation,
      immortalization, and activation of G1 CDKs and E2F. These results demonstrate
      that an essential, rate-limiting function of c-Jun in fibroblast proliferation is
      negative regulation of p53 expression, and establish a mechanistic link between c
      Jun-dependent mitogenic signaling and cell-cycle regulation.

PMID- 10072390
TI  - Constructing signal transduction pathways in Arabidopsis.

PMID- 10072389
TI  - Mos positively regulates Xe-Wee1 to lengthen the first mitotic cell cycle of
      Xenopus.
AB  - Several key developmental events occur in the first mitotic cell cycle of
      Xenopus; consequently this cycle has two gap phases and is approximately 60-75
      min in length. In contrast, embryonic cycles 2-12 consist only of S and M phases
      and are 30 min in length. Xe-Wee1 and Mos are translated and degraded in a
      developmentally regulated manner. Significantly, both proteins are present in the
      first cell cycle. We showed previously that the expression of nondegradable Mos,
      during early interphase, delays the onset of M phase in the early embryonic cell
      cycles. Here we report that Xe-Wee1 is required for the Mos-mediated M-phase
      delay. We find that Xe-Wee1 tyrosine autophosphorylation positively regulates Xe
      Wee1 and is only detected in the first 30 min of the first cell cycle. The level
      and duration of Xe-Wee1 tyrosine phosphorylation is elevated significantly when
      the first cell cycle is elongated with nondegradable Mos. Importantly, we show
      that the tyrosine phosphorylation of Xe-Wee1 is required for the Mos-mediated M
      phase delay. These findings indicate that Mos positively regulates Xe-Wee1 to
      generate the G2 phase in the first cell cycle and establish a direct link between
      the MAPK signal transduction pathway and Wee1 in vertebrates.

PMID- 10072391
TI  - Tobacco mosaic virus. Pioneering research for a century.

PMID- 10072393
TI  - Cell-to-cell and long-distance trafficking of the green fluorescent protein in
      the phloem and symplastic unloading of the protein into sink tissues.
AB  - Macromolecular trafficking within the sieve element-companion cell complex,
      phloem unloading, and post-phloem transport were studied using the jellyfish
      green fluorescent protein (GFP). The GFP gene was expressed in Arabidopsis and
      tobacco under the control of the AtSUC2 promoter. In wild-type Arabidopsis
      plants, this promoter regulates expression of the companion cell-specific AtSUC2
      sucrose-H+ symporter gene. Analyses of the AtSUC2 promoter-GFP plants
      demonstrated that the 27-kD GFP protein can traffic through plasmodesmata from
      companion cells into sieve elements and migrate within the phloem. With the
      stream of assimilates, the GFP is partitioned between different sinks, such as
      petals, root tips, anthers, funiculi, or young rosette leaves. Eventually, the
      GFP can be unloaded symplastically from the phloem into sink tissues, such as the
      seed coat, the anther connective tissue, cells of the root tip, and sink leaf
      mesophyll cells. In all of these tissues, the GFP can traffic cell to cell by
      symplastic post-phloem transport. The presented data show that plasmodesmata of
      the sieve element-companion cell complex, as well as plasmodesmata into and
      within the analyzed sinks, allow trafficking of the 27-kD nonphloem GFP protein.
      The data also show that the size exclusion limit of plasmodesmata can change
      during organ development. The results are also discussed in terms of the phloem
      mobility of assimilates and of small, low molecular weight companion cell
      proteins.

PMID- 10072394
TI  - The DNA binding site of the Dof protein NtBBF1 is essential for tissue-specific
      and auxin-regulated expression of the rolB oncogene in plants.
AB  - The Dof proteins are a large family of plant transcription factors that share a
      single highly conserved zinc finger. The tobacco Dof protein NtBBF1 was
      identified by its ability to bind to regulatory domain B in the promoter of the
      rolB oncogene. In this study, we show that the ACT T TA target sequence of NtBBF1
      in domain B is necessary for tissue-specific expression of rolB. beta
      Glucuronidase (GUS) activity of tobacco plants containing a rolB promoter-GUS
      fusion with a mutated NtBBF1 target sequence within domain B is almost completely
      suppressed in apical meristems and is severely abated in the vascular system. The
      ACT T TA motif is shown here also to be one of the cis-regulatory elements
      involved in auxin induction of rolB. The pattern of NtBBF1 expression in plants
      is remarkably similar to that of rolB, except in mesophyll cells of mature
      leaves, in which only NtBBF1 expression could be detected. Ectopic expression of
      rolB in mesophyll cells was achieved by particle gun delivery if the NtBBF1
      binding sequence was intact. These data provide evidence that in the plant, a Dof
      protein DNA binding sequence acts as a transcriptional regulatory motif, and they
      point to NtBBF1 as the protein involved in mediating tissue-specific and auxin
      inducible expression of rolB.

PMID- 10072395
TI  - The Arabidopsis photomorphogenic mutant hy1 is deficient in phytochrome
      chromophore biosynthesis as a result of a mutation in a plastid heme oxygenase.
AB  - The HY1 locus of Arabidopsis is necessary for phytochrome chromophore
      biosynthesis and is defined by mutants that show a long hypocotyl phenotype when
      grown in the light. We describe here the molecular cloning of the HY1 gene by
      using chromosome walking and mutant complementation. The product of the HY1 gene
      shows significant similarity to animal heme oxygenases and contains a possible
      transit peptide for transport to plastids. Heme oxygenase activity was detected
      in the HY1 protein expressed in Escherichia coli. Heme oxygenase catalyzes the
      oxygenation of heme to biliverdin, an activity that is necessary for phytochrome
      chromophore biosynthesis. The predicted transit peptide is sufficient to
      transport the green fluorescent protein into chloroplasts. The accumulation of
      the HY1 protein in plastids was detected by using immunoblot analysis with an
      anti-HY1 antiserum. These results indicate that the Arabidopsis HY1 gene encodes
      a plastid heme oxygenase necessary for phytochrome chromophore biosynthesis.

PMID- 10072396
TI  - Discrete domains mediate the light-responsive nuclear and cytoplasmic
      localization of Arabidopsis COP1.
AB  - The Arabidopsis CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) protein plays a critical
      role in the repression of photomorphogenesis during Arabidopsis seedling
      development. We investigated the control of COP1 partitioning between nucleus and
      cytoplasm, which has been implicated in the regulation of COP1 activity, by using
      fusion proteins between COP1 and beta-glucuronidase or the green fluorescent
      protein. Transient expression assays using onion epidermal cells and data from
      hypocotyl cells of stably transformed Arabidopsis demonstrated that COP1 carries
      a single, bipartite nuclear localization signal that functions independently of
      light. Nuclear exclusion was mediated by a novel and distinct signal, bordering
      the zinc-finger and coiled-coil motifs, that was able to redirect a heterologous
      nuclear protein to the cytoplasm. The cytoplasmic localization signal functioned
      in a light-independent manner. Light regulation of nuclear localization was
      reconstituted by combining the individual domains containing the nuclear
      localization signal and the cytoplasmic localization signal; the WD-40 repeat
      domain of COP1 was not required. However, phenotypic analysis of transgenic
      seedlings suggested that the constitutively nuclear-localized WD-40 repeat domain
      was able to mimic aspects of COP1 function, as indicated by exaggerated hypocotyl
      elongation under light conditions.

PMID- 10072397
TI  - IAR3 encodes an auxin conjugate hydrolase from Arabidopsis.
AB  - Amide-linked conjugates of indole-3-acetic acid (IAA) are putative storage or
      inactivation forms of the growth hormone auxin. Here, we describe the Arabidopsis
      iar3 mutant that displays reduced sensitivity to IAA-Ala. IAR3 is a member of a
      family of Arabidopsis genes related to the previously isolated ILR1 gene, which
      encodes an IAA-amino acid hydrolase selective for IAA-Leu and IAA-Phe. IAR3 and
      the very similar ILL5 gene are closely linked on chromosome 1 and comprise a
      subfamily of the six Arabidopsis IAA-conjugate hydrolases. The purified IAR3
      enzyme hydrolyzes IAA-Ala in vitro. iar 3 ilr1 double mutants are more resistant
      than either single mutant to IAA-amino acid conjugates, and plants overexpressing
      IAR3 or ILR1 are more sensitive than is the wild type to certain IAA-amino acid
      conjugates, reflecting the overlapping substrate specificities of the
      corresponding enzymes. The IAR3 gene is expressed most strongly in roots, stems,
      and flowers, suggesting roles for IAA-conjugate hydrolysis in those tissues.

PMID- 10072398
TI  - LeProT1, a transporter for proline, glycine betaine, and gamma-amino butyric acid
      in tomato pollen.
AB  - During maturation, pollen undergoes a period of dehydration accompanied by the
      accumulation of compatible solutes. Solute import across the pollen plasma
      membrane, which occurs via proteinaceous transporters, is required to support
      pollen development and also for subsequent germination and pollen tube growth.
      Analysis of the free amino acid composition of various tissues in tomato revealed
      that the proline content in flowers was 60 times higher than in any other organ
      analyzed. Within the floral organs, proline was confined predominantly to pollen,
      where it represented >70% of total free amino acids. Uptake experiments
      demonstrated that mature as well as germinated pollen rapidly take up proline. To
      identify proline transporters in tomato pollen, we isolated genes homologous to
      Arabidopsis proline transporters. LeProT1 was specifically expressed both in
      mature and germinating pollen, as demonstrated by RNA in situ hybridization.
      Expression in a yeast mutant demonstrated that LeProT1 transports proline and
      gamma-amino butyric acid with low affinity and glycine betaine with high
      affinity. Direct uptake and competition studies demonstrate that LeProT1
      constitutes a general transporter for compatible solutes.

PMID- 10072399
TI  - The CLAVATA1 receptor-like kinase requires CLAVATA3 for its assembly into a
      signaling complex that includes KAPP and a Rho-related protein.
AB  - The CLAVATA1 (CLV1) and CLAVATA3 (CLV3) genes are required to maintain the
      balance between cell proliferation and organ formation at the Arabidopsis shoot
      and flower meristems. CLV1 encodes a receptor-like protein kinase. We have found
      that CLV1 is present in two protein complexes in vivo. One is approximately 185
      kD, and the other is approximately 450 kD. In each complex, CLV1 is part of a
      disulfide-linked multimer of approximately 185 kD. The 450-kD complex contains
      the protein phosphatase KAPP, which is a negative regulator of CLV1 signaling,
      and a Rho GTPase-related protein. In clv1 and clv3 mutants, CLV1 is found
      primarily in the 185-kD complex. We propose that CLV1 is present as an inactive
      disulfide-linked heterodimer and that CLV3 functions to promote the assembly of
      the active 450-kD complex, which then relays signal transduction through a Rho
      GTPase.

PMID- 10072400
TI  - Mutations in FIE, a WD polycomb group gene, allow endosperm development without
      fertilization.
AB  - A fundamental problem in biology is to understand how fertilization initiates
      reproductive development. Higher plant reproduction is unique because two
      fertilization events are required for sexual reproduction. First, a sperm must
      fuse with the egg to form an embryo. A second sperm must then fuse with the
      adjacent central cell nucleus that replicates to form an endosperm, which is the
      support tissue required for embryo and/or seedling development. Here, we report
      cloning of the Arabidopsis FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) gene. The
      FIE protein is a homolog of the WD motif-containing Polycomb proteins from
      Drosophila and mammals. These proteins function as repressors of homeotic genes.
      A female gametophyte with a loss-of-function allele of fie undergoes replication
      of the central cell nucleus and initiates endosperm development without
      fertilization. These results suggest that the FIE Polycomb protein functions to
      suppress a critical aspect of early plant reproduction, namely, endosperm
      development, until fertilization occurs.

PMID- 10072401
TI  - Isolation and characterization of SYN1, a RAD21-like gene essential for meiosis
      in Arabidopsis.
AB  - The proper pairing, recombination, and segregation of chromosomes are central to
      meiosis and sexual reproduction. The syn1 mutation was previously identified as a
      synaptic mutant in a T-DNA-tagged population of plants. SYN1 has been isolated
      and found to exhibit similarity to Schizosaccharomyces pombe RAD21 and RAD21-like
      proteins, which are required for chromosome condensation and sister chromatid
      cohesion during mitosis. Plants homozygous for syn1 are male and female sterile
      and show defects in chromosome condensation and pairing beginning at leptonema of
      meiosis I. Fragmentation of the chromosomes was observed at metaphase I.
      Alternative promoters produced two SYN1 transcripts. One transcript was expressed
      at low levels in most tissues, whereas the other was expressed only in prebolting
      buds. DNA blot analyses suggest that Arabidopsis contains a small RAD21 gene
      family. Consistent with the DNA blot data, a second Arabidopsis RAD21-like gene
      has been identified. These results suggest that different RAD21-like proteins
      play essential roles in chromosome condensation and pairing during both meiosis
      and mitosis.

PMID- 10072402
TI  - The involvement of cysteine proteases and protease inhibitor genes in the
      regulation of programmed cell death in plants.
AB  - Programmed cell death (PCD) is a process by which cells in many organisms die.
      The basic morphological and biochemical features of PCD are conserved between the
      animal and plant kingdoms. Cysteine proteases have emerged as key enzymes in the
      regulation of animal PCD. Here, we show that in soybean cells, PCD-activating
      oxidative stress induced a set of cysteine proteases. The activation of one or
      more of the cysteine proteases was instrumental in the PCD of soybean cells.
      Inhibition of the cysteine proteases by ectopic expression of cystatin, an
      endogenous cysteine protease inhibitor gene, inhibited induced cysteine protease
      activity and blocked PCD triggered either by an avirulent strain of Pseudomonas
      syringae pv glycinea or directly by oxidative stress. Similar expression of
      serine protease inhibitors was ineffective. A glutathione S-transferase-cystatin
      fusion protein was used to purify and characterize the induced proteases. Taken
      together, our results suggest that plant PCD can be regulated by activity poised
      between the cysteine proteases and the cysteine protease inhibitors. We also
      propose a new role for proteinase inhibitor genes as modulators of PCD in plants.

PMID- 10072403
TI  - The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by
      vernalization and methylation.
AB  - A MADS box gene, FLF (for FLOWERING LOCUS F ), isolated from a late-flowering, T
      DNA-tagged Arabidopsis mutant, is a semidominant gene encoding a repressor of
      flowering. The FLF gene appears to integrate the vernalization-dependent and
      autonomous flowering pathways because its expression is regulated by genes in
      both pathways. The level of FLF mRNA is downregulated by vernalization and by a
      decrease in genomic DNA methylation, which is consistent with our previous
      suggestion that vernalization acts to induce flowering through changes in gene
      activity that are mediated through a reduction in DNA methylation. The flf-1
      mutant requires a greater than normal amount of an exogenous gibberellin (GA3) to
      decrease flowering time compared with the wild type or with vernalization
      responsive late-flowering mutants, suggesting that the FLF gene product may block
      the promotion of flowering by GAs. FLF maps to a region on chromosome 5 near the
      FLOWERING LOCUS C gene, which is a semidominant repressor of flowering in late
      flowering ecotypes of Arabidopsis.

PMID- 10072404
TI  - Overexpression of BiP in tobacco alleviates endoplasmic reticulum stress.
AB  - To study the role of the lumenal binding protein (BiP) in the transport and
      secretion of proteins, we have produced plants with altered BiP levels.
      Transgenic plants overexpressing BiP showed dramatically increased BiP mRNA
      levels but only a modest increase in BiP protein levels. The presence of
      degradation products in BiP overproducers suggests a regulatory mechanism that
      increases protein turnover when BiP is abundant. Antisense inhibition of BiP
      synthesis was not successful, demonstrating that even a minor reduction in the
      basal BiP level is deleterious to cell viability. Overexpression of BiP leads to
      downregulation of the basal transcript levels of endogenous BiP genes and greatly
      reduces the unfolded protein response. The data confirm that BiP transcription is
      regulated via a feedback mechanism that involves monitoring of BiP protein
      levels. To test BiP activity in vivo, we designed a functional assay, using the
      secretory protein alpha-amylase and a cytosolic enzyme as a control for cell
      viability. During tunicamycin treatment, an overall reduction of alpha-amylase
      synthesis was observed when compared with the cytosolic marker. We show that the
      tunicamycin effect is due to the depletion of BiP in the endoplasmic reticulum
      because coexpressed BiP alone is able to restore efficient alpha-amylase
      synthesis. This is a novel assay to monitor BiP activity in promoting secretory
      protein synthesis in vivo.

PMID- 10072405
TI  - Stochastic and nonstochastic post-transcriptional silencing of chitinase and beta
      1,3-glucanase genes involves increased RNA turnover-possible role for ribosome
      independent RNA degradation.
AB  - Stochastic and nonstochastic post-transcriptional gene silencing (PTGS) in
      Nicotiana sylvestris plants carrying tobacco class I chitinase (CHN) and beta-1,3
      glucanase transgenes differs in incidence, stability, and pattern of expression.
      Measurements with inhibitors of RNA synthesis (cordycepin, actinomycin D, and
      alpha-amanitin) showed that both forms of PTGS are associated with increased
      sequence-specific degradation of transcripts, suggesting that increased RNA
      turnover may be a general feature of PTGS. The protein synthesis inhibitors
      cycloheximide and verrucarin A did not inhibit degradation of CHN RNA targeted
      for PTGS, confirming that PTGS-related RNA degradation does not depend on ongoing
      protein synthesis. Because verrucarin A, unlike cycloheximide, dissociates mRNA
      from ribosomes, our results also suggest that ribosome-associated RNA degradation
      pathways may not be involved in CHN PTGS.

PMID- 10072406
TI  - Divinyl ether fatty acid synthesis in late blight-diseased potato leaves.
AB  - We conducted a study of the patterns and dynamics of oxidized fatty acid
      derivatives (oxylipins) in potato leaves infected with the late-blight pathogen
      Phytophthora infestans. Two 18-carbon divinyl ether fatty acids, colneleic acid
      and colnelenic acid, accumulated during disease development. To date, there are
      no reports that such compounds have been detected in higher plants. The divinyl
      ether fatty acids accumulate more rapidly in potato cultivar Matilda (a cultivar
      with increased resistance to late blight) than in cultivar Bintje, a susceptible
      cultivar. Colnelenic acid reached levels of up to approximately 24 nmol (7
      microgram) per g fresh weight of tissue in infected leaves. By contrast, levels
      of members of the jasmonic acid family did not change significantly during
      pathogenesis. The divinyl ethers also accumulated during the incompatible
      interaction of tobacco with tobacco mosaic virus. Colneleic and colnelenic acids
      were found to be inhibitory to P. infestans, suggesting a function in plant
      defense for divinyl ethers, which are unstable compounds rarely encountered in
      biological systems.

PMID- 10072407
TI  - Identification of regions in alleles of the flax rust resistance gene L that
      determine differences in gene-for-gene specificity.
AB  - Thirteen alleles (L, L1 to L11, and LH) from the flax L locus, which encode
      Toll/interleukin-1 receptor homology-nucleotide binding site-leucine-rich repeat
      (TIR-NBS-LRR) rust resistance proteins, were sequenced and compared to provide
      insight into their evolution and into the determinants of gene-for-gene
      resistance specificity. The predicted L6 and L11 proteins differ solely in the
      LRR region, whereas L6 and L7 differ solely in the TIR region. Thus, specificity
      differences between alleles can be determined by both the LRR and TIR regions.
      Functional analysis in transgenic plants of recombinant alleles constructed in
      vitro provided further information: L10-L2 and L6-L2 recombinants, encoding the
      LRR of L2, conferred L2 resistance specificity, and an L2-L10 recombinant,
      encoding the LRR of L10, conferred a novel specificity. The sequence comparisons
      also indicate that the evolution of L alleles has probably involved reassortment
      of variation, resulting from accumulated point mutations, by intragenic
      recombination. In addition, large deletion events have occurred in the LRR
      encoding regions of L1 and L8, and duplication events have occurred in the LRR
      encoding region of L2.

PMID- 10072408
TI  - Rising incidence of hepatocellular carcinoma in the United States.
AB  - BACKGROUND AND METHODS: Clinical observations have suggested that the number of
      cases of hepatocellular carcinoma has increased in the United States. We analyzed
      data from the Surveillance, Epidemiology, and End Results (SEER) data base to
      determine the age-adjusted incidence of hepatocellular carcinoma from 1976 to
      1995, data from the U.S. vital-statistics data base to determine age-adjusted
      mortality rates from 1981 to 1995, and data from the Department of Veterans
      Affairs to determine age-adjusted rates of hospitalization for the disease from
      1983 to 1997. RESULTS: The incidence of histologically proved hepatocellular
      carcinoma increased from 1.4 per 100,000 population (95 percent confidence
      interval, 1.3 to 1.4) for the period from 1976 to 1980 to 2.4 per 100,000 (95
      percent confidence interval, 2.3 to 2.4) for the period from 1991 to 1995. Among
      black men, the incidence was 6.1 per 100,000 for the period from 1991 to 1995,
      and among white men, it was 2.8 per 100,000. There was a 41 percent increase in
      the mortality rate from primary liver cancer and a 46 percent increase in the
      proportion of hospitalizations attributable to this disease during the periods
      studied. The incidence increased significantly among younger persons (40 to 60
      years old) during the period from 1991 to 1995 as compared with earlier periods.
      CONCLUSIONS: An increase in the number of cases of hepatocellular carcinoma has
      occurred in the United States over the past two decades. The age-specific
      incidence of this cancer has progressively shifted toward younger people.

PMID- 10072409
TI  - Endoscopic retreatment compared with surgery in patients with recurrent bleeding
      after initial endoscopic control of bleeding ulcers.
AB  - BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic
      ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective,
      randomized study, we compared endoscopic retreatment with surgery after initial
      endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our
      hospital with bleeding peptic ulcers underwent endoscopy to reestablish
      hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1
      patient with cardiac arrest were excluded from the study; 48 patients were
      randomly assigned to undergo immediate endoscopic retreatment and 44 were
      assigned to undergo surgery. The type of operation used was left to the surgeon.
      Bleeding was considered to have recurred in the event of any one of the
      following: vomiting of fresh blood, hypotension and melena, or a requirement for
      more than four units of blood in the 72-hour period after endoscopic treatment.
      RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had
      long-term control of bleeding. Thirteen underwent salvage surgery, 11 because
      retreatment failed and 2 because of perforations resulting from
      thermocoagulation. Five patients in the endoscopy group died within 30 days, as
      compared with eight patients in the surgery group (P=0.37). Seven patients in the
      endoscopy group (including 6 who underwent salvage surgery) had complications, as
      compared with 16 in the surgery group (P=0.03). The duration of hospitalization,
      the need for hospitalization in the intensive care unit and the resultant
      duration of that stay, and the number of blood transfusions were similar in the
      two groups. In multivariate analysis, hypotension at randomization (P=0.01) and
      an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of
      the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic
      ulcers and recurrent bleeding after initial endoscopic control of bleeding,
      endoscopic retreatment reduces the need for surgery without increasing the risk
      of death and is associated with fewer complications than is surgery.

PMID- 10072410
TI  - Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's
      disease.
AB  - BACKGROUND: Drug-induced psychosis is a difficult problem to manage in patients
      with Parkinson's disease. Multiple open-label studies have reported that
      treatment with clozapine at low doses ameliorates psychosis without worsening
      parkinsonism. METHODS: We conducted a randomized, double-blind, placebo
      controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients
      at six sites over a period of 14 months. The patients (mean age, 72 years) had
      idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks'
      duration. All the patients continued to receive fixed doses of antiparkinsonian
      drugs during the four weeks of the trial. Blood counts were monitored weekly in
      all the patients. RESULTS: The mean dose of clozapine was 24.7 mg per day. The
      patients in the clozapine group had significantly more improvement than those in
      the placebo group in all three of the measures used to determine the severity of
      psychosis. The mean (+/-SE) scores on the Clinical Global Impression Scale
      improved by 1.6+/-0.3 points for the patients receiving clozapine, as compared
      with 0.5+/-0.2 point for those receiving placebo (P<0.001). The score on the
      Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the patients
      receiving clozapine, as compared with 2.6+/-1.3 points for those receiving
      placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms
      improved by 11.8+/-2.0 points for the patients receiving clozapine, as compared
      with 3.8+/-1.9 points for those receiving placebo (P=0.01). Seven patients
      treated with clozapine had an improvement of at least three on the seven-point
      Clinical Global Impression Scale, as compared with only one patient given
      placebo. Clozapine treatment improved tremor and had no deleterious effect on the
      severity of parkinsonism. In one patient, clozapine was discontinued because of
      leukopenia. CONCLUSIONS: Clozapine, at daily doses of 50 mg or less, is safe and
      significantly improves drug-induced psychosis without worsening parkinsonism.

PMID- 10072411
TI  - Liposomal amphotericin B for empirical therapy in patients with persistent fever
      and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses
      Study Group.
AB  - BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is
      administered empirically for the early treatment and prevention of clinically
      occult invasive fungal infections. However, breakthrough fungal infections can
      develop despite treatment, and amphotericin B has substantial toxicity. METHODS:
      We conducted a randomized, double-blind, multicenter trial comparing liposomal
      amphotericin B with conventional amphotericin B as empirical antifungal therapy.
      RESULTS: The mean duration of therapy was 10.8 days for liposomal amphotericin B
      (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The
      composite rates of successful treatment were similar (50 percent for liposomal
      amphotericin B and 49 percent for conventional amphotericin B) and were
      independent of the use of antifungal prophylaxis or colony-stimulating factors.
      The outcomes were similar with liposomal amphotericin B and conventional
      amphotericin B with respect to survival (93 percent and 90 percent,
      respectively), resolution of fever (58 percent and 58 percent), and
      discontinuation of the study drug because of toxic effects or lack of efficacy
      (14 percent and 19 percent). There were fewer proved breakthrough fungal
      infections among patients treated with liposomal amphotericin B (11 patients [3.2
      percent]) than among those treated with conventional amphotericin B (27 patients
      [7.8 percent], P=0.009). With the liposomal preparation significantly fewer
      patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors
      (18 percent vs. 54 percent), and other reactions, including hypotension,
      hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine
      level two times the upper limit of normal) were significantly less frequent among
      patients treated with liposomal amphotericin B (19 percent) than among those
      treated with conventional amphotericin B (34 percent, P<0.001). CONCLUSIONS:
      Liposomal amphotericin B is as effective as conventional amphotericin B for
      empirical antifungal therapy in patients with fever and neutropenia, and it is
      associated with fewer breakthrough fungal infections, less infusion-related
      toxicity, and less nephrotoxicity.

PMID- 10072412
TI  - Images in clinical medicine. Endoscopy in its infancy.

PMID- 10072413
TI  - The cost effectiveness of strategies for the treatment of intestinal parasites in
      immigrants.
AB  - BACKGROUND: Currently, more than 600,000 immigrants enter the United States each
      year from countries where intestinal parasites are endemic. At entry persons with
      parasitic infections may be asymptomatic, and stool examinations are not a
      sensitive method of screening for parasitosis. Albendazole is a new, broad
      spectrum antiparasitic drug, which was approved recently by the Food and Drug
      Administration. International trials have shown albendazole to be safe and
      effective in eradicating many parasites. In the United States there is now
      disagreement about whether to screen all immigrants for parasites, treat all
      immigrants presumptively, or do nothing unless they have symptoms. METHODS: We
      compared the costs and benefits of no preventive intervention (watchful waiting)
      with those of universal screening or presumptive treatment with 400 mg of
      albendazole per day for five days. Those at risk were defined as immigrants to
      the United States from Asia, the Middle East, sub-Saharan Africa, Eastern Europe,
      and Latin America and the Caribbean. Cost effectiveness was expressed both in
      terms of the cost of treatment per disability-adjusted life-year (DALY) averted
      (one DALY is defined as the loss of one year of healthy life to disease) and in
      terms of the cost per hospitalization averted. RESULTS: As compared with watchful
      waiting, presumptive treatment of all immigrants at risk for parasitosis would
      avert at least 870 DALYs, prevent at least 33 deaths and 374 hospitalizations,
      and save at least $4.2 million per year. As compared with watchful waiting,
      screening would cost $159,236 per DALY averted. CONCLUSIONS: Presumptive
      administration of albendazole to all immigrants at risk for parasitosis would
      save lives and money. Universal screening, with treatment of persons with
      positive stool examinations, would save lives but is less cost effective than
      presumptive treatment.

PMID- 10072414
TI  - Treatment of attention-deficit-hyperactivity disorder.

PMID- 10072415
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-1999. A 50-year-old woman with severe diarrhea during radiation
      treatment for resected metastatic melanoma.

PMID- 10072416
TI  - The increasing incidence of hepatocellular carcinoma.

PMID- 10072417
TI  - Management of severe ulcer rebleeding.

PMID- 10072418
TI  - Managing psychosis in patients with Parkinson's disease.

PMID- 10072420
TI  - Is informed consent always necessary for randomized, controlled trials?  .

PMID- 10072422
TI  - In vivo nuclease hypersensitivity studies reveal multiple sites of parental
      origin-dependent differential chromatin conformation in the 150 kb SNRPN
      transcription unit.
AB  - Human chromosome region 15q11-q13 contains a cluster of oppositely imprinted
      genes. Loss of the paternal or the maternal alleles by deletion of the region or
      by uniparental disomy 15 results in Prader-Willi syndrome (PWS) or Angelman
      syndrome (AS), respectively. Hence, the two phenotypically distinct
      neurodevelopmental disorders are caused by the lack of products of imprinted
      genes. Subsets of PWS and AS patients exhibit 'imprinting mutations', such as
      small microdeletions within the 5' region of the small nuclear ribonucleoprotein
      polypeptide N ( SNRPN ) transcription unit which affect the transcriptional
      activity and methylation status of distant imprinted genes throughout 15q11-q13
      in cis. To elucidate the mechanism of these long-range effects, we have analyzed
      the chromatin structure of the 150 kb SNRPN transcription unit for DNase I- and
      Msp I-hypersensitive sites. By using an in vivo approach on lymphoblastoid cell
      lines from PWS and AS individuals, we discovered that the SNRPN exon 1 is flanked
      by prominent hypersensitive sites on the paternal allele, but is completely
      inaccessible to nucleases on the maternal allele. In contrast, we identified
      several regions of increased nuclease hypersensitivity on the maternal allele,
      one of which coincides with the AS minimal microdeletion region and another lies
      in intron 1 immediately downstream of the paternal-specific hypersensitive sites.
      At several sites, parental origin-specific nuclease hypersensitivity was found to
      be correlated with hypermethylation on the allele contributed by the other
      parent. The differential parental origin-dependent chromatin conformations might
      govern access of regulatory protein complexes and/or RNAs which could mediate
      interaction of the region with other genes.

PMID- 10072423
TI  - A wide variety of mutations in the parkin gene are responsible for autosomal
      recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group
      and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the
      monogenic forms of Parkinson's disease (PD), was initially described in Japan. It
      is characterized by early onset (before age 40), marked response to levodopa
      treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was
      recently identified and designated parkin. We have analysed the 12 coding exons
      of the parkin gene in 35 mostly European families with early onset autosomal
      recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be
      demonstrated. By direct sequencing of the exons in the index patients of the
      remaining 34 families, eight previously undescribed point mutations (homozygous
      or heterozygous) were detected in eight families that included 20 patients. The
      mutations segregated with the disease in the families and were not detected on
      110-166 control chromosomes. Four mutations caused truncation of the parkin
      protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one
      a nonsense mutation (Trp453Stop). The other four were missense mutations
      (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids
      that are important for the function of the parkin protein, since they result in
      the same phenotype as truncating mutations or homozygous exon deletions. Mean age
      at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in
      the parkin gene are therefore not invariably associated with early onset
      parkinsonism. In many patients, the phenotype is indistinguishable from that of
      idiopathic PD. This study has shown that a wide variety of different mutations in
      the parkin gene are a common cause of autosomal recessive parkinsonism in Europe
      and that different types of point mutations seem to be more frequently
      responsible for the disease phenotype than are deletions.

PMID- 10072424
TI  - Cloning and characterization of a secreted frizzled-related protein that is
      expressed by the retinal pigment epithelium.
AB  - The Wnt/frizzled cell signaling pathway has been implicated in the determination
      of polarity in a number of systems, including the Drosophila retina. The
      vertebrate retina develops from an undifferentiated neuroepithelium into an
      organized and laminated structure that demonstrates a high degree of polarity at
      both the tissue and cellular levels. In the process of searching for molecules
      that are preferentially expressed by the vertebrate retinal pigment epithelium
      (RPE), we identified secreted frizzled-related protein 5 (SFRP5), a member of the
      SFRP family that appears to act by modulating Wnt signal transduction. SFRP5 is
      highly expressed by RPE cells, and is also expressed in the pancreas. Within the
      retina, the related molecule SFRP2 is expressed specifically by cells of the
      inner nuclear layer. Thus, photoreceptors are likely to be bathed by two opposing
      gradients of SFRP molecules. Consistent with SFRP5 's postulated role in
      modulating Wnt signaling in the retina, it inhibits the ability of Xwnt-8 mRNA to
      induce axis duplication in Xenopus embryos. The human SFRP5 gene consists of
      three coding exons and it maps to chromosome 10q24.1; human SFRP2 maps to 4q31.3.
      Based on the biology and complementary expression patterns of SFRP2 and SFRP5, we
      suggest that they may be involved in determining the polarity of photoreceptor,
      and perhaps other, cells in the retina.

PMID- 10072425
TI  - Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins
      and co-localization with the SNF protein BRM in the nucleus.
AB  - The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial
      sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1
      or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional
      co-activator and the SSX proteins as co-repressors. Here we have investigated the
      functional domains of the proteins. The SYT protein has a novel conserved 54
      amino acid domain at the N-terminus of the protein (the SNH domain) which is
      found in proteins from a wide variety of species, and a C-terminal domain, rich
      in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the
      transcriptional activator sequences. Deletion of the SNH domain results in a more
      active transcriptional activator, suggesting that this domain acts as an
      inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX
      translocation protein contributes a transcriptional repressor domain to the
      protein. Thus, the fusion protein has transcriptional activating and repressing
      domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM
      co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with
      SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of
      how the SYT protein activates gene transcription.

PMID- 10072426
TI  - Characterization of dystrophin and utrophin diversity in the mouse.
AB  - Utrophin is a 400 kDa autosomal homolog of dystrophin and a component of the
      submembranous cytoskeleton. While multiple dystrophin isoforms have been
      identified along with alternatively spliced products, to date only two different
      mRNA species of utrophin have been identified. To determine the degree of
      evolutionary conservation between dystrophin and utrophin isoforms, we have
      compared their expression patterns in adult mice. Northern blot analysis of
      multiple adult tissues confirmed that only two major sizes of transcripts are
      produced from each gene: 13 and 5.5 kb from utrophin and 14 and 4.8 kb from
      dystrophin. However, western blot analysis detected several putative short
      utrophin isoforms that may be homologs of the dystrophin isoforms Dp140, Dp116
      and Dp71. We also identified an alternatively spliced utrophin transcript that
      lacks the equivalent of the alternatively spliced dystrophin exon 71. Finally, we
      demonstrated that the C-terminal domain of utrophin targeted to neuromuscular
      junctions in normal mice, but localized to the sarcolemma efficiently only in the
      absence of dystrophin. Our results provide further evidence for a common
      evolutionary origin of the utrophin and dystrophin genes.

PMID- 10072427
TI  - A genome-wide screen for asthma-associated quantitative trait loci in a mouse
      model of allergic asthma.
AB  - Asthma is the most common illness of childhood, affecting one child in seven in
      the UK. Asthma has a genetic basis, but genetic studies of asthma in humans are
      confounded by uncontrolled environmental factors, varying penetrance and
      phenotypic pleiotropy. An animal model of asthma would offer controlled exposure,
      limited and consistent genetic variation, and unlimited size of sibships.
      Following immunization and subsequent challenge with ovalbumin, the Biozzi BP2
      mouse shows features of asthma, including airway inflammation, eosinophil
      infiltration and non-specific bronchial responsiveness. In order to identify
      genetic loci influencing these traits, a cross was made between BP2 and BALB/c
      mice, and a genome-wide screen carried out in the F2progeny of the F1intercross.
      Five potentially linked loci were identified, four of which corresponded to human
      regions of syntenic homology that previously have shown linkage to asthma
      associated traits.

PMID- 10072428
TI  - Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer
      and colorectal cancer.
AB  - Inherited mutations in the E-cadherin gene ( CDH1 ) were described recently in
      three Maori kindreds with familial gastric cancer. Familial gastric cancer is
      genetically heterogeneous and it is not clear what proportion of gastric cancer
      susceptibility in non-Maori populations is due to germline CDH1 mutations.
      Therefore, we screened eight familial gastric cancer kindreds of British and
      Irish origin for germline CDH1 mutations, by SSCP analysis of all 16 exons and
      flanking sequences. Each family contained: (i) two cases of gastric cancer in
      first degree relatives with one affected before age 50 years; or (ii) three or
      more cases of gastric cancer. Novel germline CDH1 mutations (a nonsense and a
      splice site) were detected in two families (25%). Both mutations were predicted
      to truncate the E-cadherin protein in the signal peptide domain. In one family
      there was evidence of non-penetrance and susceptibility to both gastric and
      colorectal cancer; thus, in addition to six cases of gastric cancer, a CDH1
      mutation carrier developed colorectal cancer at age 30 years. We have confirmed
      that germline mutations in the CDH1 gene cause familial gastric cancer in non
      Maori populations. However, only a minority of familial gastric cancers can be
      accounted for by CDH1 mutations. Loss of E-cadherin function has been implicated
      in the pathogenesis of sporadic colorectal and other cancers, and our findings
      provide evidence that germline CDH1 mutations predispose to early onset
      colorectal cancer. Thus, CDH1 should be investigated as a cause of inherited
      susceptibility to both gastric and colorectal cancers.

PMID- 10072429
TI  - Bex1, a gene with increased expression in parthenogenetic embryos, is a member of
      a novel gene family on the mouse X chromosome.
AB  - Parthenogenetic and normal blastocysts were compared using differential display
      analysis as a means to identify new imprinted genes. A single gene was identified
      with increased expression in parthenogenetic blastocysts, suggesting it might be
      an imprinted gene expressed from the maternally inherited allele. The gene, named
      Bex1 (brainexpressedX-linked gene), maps near Plp on the mouse X chromosome and
      to Xq22 in humans. Database homology searches revealed two additional
      uncharacterized cDNAs similar to Bex1 that were named Bex2 and Bex3. Allele
      specific expression analysis of Bex1 using F1 blastocysts indicated an excess of
      transcript expressed from the maternally inherited allele compared with the
      paternally inherited allele. This excess level of transcript derived from the
      maternally inherited allele may be due to imprinted X inactivation of the
      paternally inherited allele in the extraembryonic lineages of female embryos
      rather than a result of genomic imprinting.

PMID- 10072430
TI  - Excess of high activity monoamine oxidase A gene promoter alleles in female
      patients with panic disorder.
AB  - A genetic contribution to the pathogenesis of panic disorder has been
      demonstrated by clinical genetic studies. Molecular genetic studies have focused
      on candidate genes suggested by the molecular mechanisms implied in the action of
      drugs utilized for therapy or in challenge tests. One class of drugs effective in
      the treatment of panic disorder is represented by monoamine oxidase A inhibitors.
      Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate
      gene. In the present study we investigated a novel repeat polymorphism in the
      promoter of the monoamine oxidase A gene for association with panic disorder in
      two independent samples (German sample, n = 80; Italian sample, n = 129). Two
      alleles (3 and 4 repeats) were most common and constituted >97% of the observed
      alleles. Functional characterization in a luciferase assay demonstrated that the
      longer alleles (3a, 4 and 5) were more active than allele 3. Among females of
      both the German and the Italian samples of panic disorder patients (combined, n =
      209) the longer alleles (3a, 4 and 5) were significantly more frequent than among
      females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df
      = 1, P = 0.001). Together with the observation that inhibition of monoamine
      oxidase A is clinically effective in the treatment of panic disorder these
      findings suggest that increased monoamine oxidase A activity is a risk factor for
      panic disorder in female patients.

PMID- 10072431
TI  - Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital
      hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcriptionfactor
      gene.
AB  - Congenital hydrocephalus is an etiologically diverse, poorly understood, but
      relatively common birth defect. Most human cases are sporadic with familial forms
      showing considerable phenotypic and etiologic heterogeneity. We have studied the
      autosomal recessive mouse mutation congenital hydrocephalus ( ch ) to identify
      candidate human hydrocephalus genes and their modifiers. ch mice have a
      congenital, lethal hydrocephalus in association with multiple developmental
      defects, notably skeletal defects, in tissues derived from the cephalic neural
      crest. We utilized positional cloning methods to map ch in the vicinity of
      D13Mit294 and confirm that the ch phenotype is caused by homozygosity for a
      nonsense mutation in a gene encoding a winged helix/forkhead transcription factor
      ( Mf1 ). Based on linked genetic markers, we performed detailed phenotypic
      characterization of mutant homozygotes and heterozygotes to demonstrate the
      pleiotropic effects of the mutant gene. Surprisingly, ch heterozygotes have the
      glaucoma-related distinct phenotype of multiple anterior segment defects
      resembling Axenfeld-Rieger anomaly. We also localized a second member of this
      gene family ( Hfh1 ), a candidate for other developmental defects, approximately
      470 kb proximal to Mf1.

PMID- 10072432
TI  - Genome-wide screen for systemic lupus erythematosus susceptibility genes in
      multiplex families.
AB  - Systemic lupus erythematosus (SLE) is the prototype of human autoimmune diseases.
      Its genetic component has been suggested by familial aggregation (lambdas = 20)
      and twin studies. We have screened the human genome to localize genetic intervals
      that may contain lupus susceptibility loci in a sample of 188 lupus patients
      belonging to 80 lupus families with two or more affected relatives per family
      using the ABI Prism linkage mapping set which includes 350 polymorphic markers
      with an average spacing of 12 cM. Non-parametric multipoint linkage analysis
      suggests evidence for predisposing loci on chromosomes 1 and 18. However, no
      single locus with overwhelming evidence for linkage was found, suggesting that
      there are no 'major' susceptibility genes segregating in families with SLE, and
      that the genetic etiology is more likely to result from the action of several
      genes of moderate effect. Furthermore, the support for a gene in the 1q44 region
      as well as in the 1p36 region is clearly found only in the Mexican American
      families with SLE but not in families of Caucasian ethnicity, suggesting that
      consideration of each ethnic group separately is crucial.

PMID- 10072433
TI  - Inner ear and kidney anomalies caused by IAP insertion in an intron of the Eya1
      gene in a mouse model of BOR syndrome.
AB  - A spontaneous mutation causing deafness and circling behavior was discovered in a
      C3H/HeJ colony of mice at the Jackson Laboratory. Pathological analysis of mutant
      mice revealed gross morphological abnormalities of the inner ear, and also
      dysmorphic or missing kidneys. The deafness and abnormal behavior were shown to
      be inherited as an autosomal recessive trait and mapped to mouse chromosome 1
      near the position of the Eya1 gene. The human homolog of this gene, EYA1, has
      been shown to underly branchio-oto-renal (BOR) syndrome, an autosomal dominant
      disorder characterized by hearing loss with associated branchial and renal
      anomalies. Molecular analysis of the Eya1 gene in mutant mice revealed the
      insertion of an intracisternal A particle (IAP) element in intron 7. The presence
      of the IAP insertion was associated with reduced expression of the normal Eya1
      message and formation of additional aberrant transcripts. The hypomorphic nature
      of the mutation may explain its recessive inheritance, if protein levels in
      homozygotes, but not heterozygotes, are below a critical threshold needed for
      normal developmental function. The new mouse mutation is designated Eya1(bor) to
      denote its similarity to human BOR syndrome, and will provide a valuable model
      for studying mutant gene expression and etiology.

PMID- 10072434
TI  - Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient
      cellular carnitine uptake in primary carnitine deficiency.
AB  - Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal
      recessive disease characterized by low serum and intracellular concentrations of
      carnitine. CDSP may present with acute metabolic derangement simulating Reye's
      syndrome within the first 2 years of life. After 3 years of age, patients with
      CDSP may present with cardiomyopathy and muscle weakness. A linkage with D5S436
      in 5q was reported in a family. A recently cloned homologue of the organic cation
      transporter, OCTN2, which has sodium-dependent carnitine uptake properties, was
      also mapped to the same locus. We screened for mutation in OCTN2 in a confirmed
      CDSP family. One truncating mutation (Trp132Stop) and one missense mutation
      (Pro478Leu) of OCTN2 were identified together with two silent polymorphisms.
      Expression of the mutant cDNAs revealed virtually no uptake activity for both
      mutations. Our data indicate that mutations in OCTN2 are responsible for CDSP.
      Identification of the underlying gene in this disease will allow rapid detection
      of carriers and postnatal diagnosis of affected patients.

PMID- 10072435
TI  - MLH1 promoter methylation and gene silencing is the primary cause of
      microsatellite instability in sporadic endometrial cancers.
AB  - Defective DNA mismatch repair in human tumors leads to genome-wide instability of
      microsatellite repeats and a molecular phenotype referred to as microsatellite
      instability (MSI). MSI has been reported in a variety of cancers and is a
      consistent feature of tumors from patients with hereditary non-polyposis
      colorectal cancer. Approximately 20% of cancers of the uterine endometrium, the
      fifth most common cancer of women world-wide, exhibit MSI. Although the frequency
      of MSI is higher in endometrial cancers than in any other common malignancy, the
      genetic basis of MSI in these tumors has remained elusive. We investigated the
      role that methylation of the MLH1 DNA mismatch repair gene plays in the genesis
      of MSI in a large series of sporadic endometrial cancers. The MLH1 promoter was
      methylated in 41 of 53 (77%) MSI-positive cancers investigated. In MSI-negative
      tumors on the other hand, there was evidence for limited methylation in only one
      of 11 tumors studied. Immunohistochemical investigation of a subset of the tumors
      revealed that methylation of the MLH1 promoter in MSI-positive tumors was
      associated with loss of MLH1 expression. Immunohistochemistry proved that two MSI
      positive tumors lacking MLH1 methylation failed to express the MSH2 mismatch
      repair gene. Both of these cancers came from women who had family and medical
      histories suggestive of inherited cancer susceptibility. These observations
      suggest that epigenetic changes in the MLH1 locus account for MSI in most cases
      of sporadic endometrial cancers and provide additional evidence that the MSH2
      gene may contribute substantially to inherited forms of endometrial cancer.

PMID- 10072436
TI  - Genetic mapping of a maternal locus responsible for familial hydatidiform moles.
AB  - Hydatidiform mole (HM) is the product of an aberrant human pregnancy in which
      there is an abnormal embryonic development and proliferation of placental villi.
      The incidence of HM varies between ethnic groups, and occurs in 1 in every 1500
      pregnancies in the USA. All HM cases are sporadic, except for extremely rare
      familial cases. The exact mechanisms leading to molar pregnancies are unknown. We
      previously postulated that women with recurrent hydatidiform moles are homozygous
      for an autosomal recessive defective gene. To map this gene genetically, we
      initiated a genome-wide scan with highly polymorphic short tandem repeats in
      individuals from two families with recurrent HM. Here, we demonstrate that a
      defective maternal gene is responsible for recurrent HM. This gene resides on
      chromosome 19q13.3-13.4 in a 15.2 cM interval flanked by D19S924 and D19S890. The
      identification of a gene for HM adds new insights into the molecular genetics of
      early embryogenesis and may be relevant to the large number of patients with
      sporadic HM.

PMID- 10072437
TI  - Evidence for proteasome involvement in polyglutamine disease: localization to
      nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in
      vitro.
AB  - Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD),
      is one of at least eight inherited neurodegenerative diseases caused by expansion
      of a polyglutamine tract in the disease protein. Here we present two lines of
      evidence implicating the ubiquitin-proteasome pathway in SCA3/MJD pathogenesis.
      First, studies of both human disease tissue and in vitro models showed
      redistribution of the 26S proteasome complex into polyglutamine aggregates. In
      neurons from SCA3/MJD brain, the proteasome localized to intranuclear inclusions
      containing the mutant protein, ataxin-3. In transfected cells, the proteasome
      redistributed into inclusions formed by three expanded polyglutamine proteins: a
      pathologic ataxin-3 fragment, full-length mutant ataxin-3 and an unrelated GFP
      polyglutamine fusion protein. Inclusion formation by the full-length mutant
      ataxin-3 required nuclear localization of the protein and occurred within
      specific subnuclear structures recently implicated in the regulation of cell
      death, promyelocytic leukemia antigen oncogenic domains. In a second set of
      experiments, inhibitors of the proteasome caused a repeat length-dependent
      increase in aggregate formation, implying that the proteasome plays a direct role
      in suppressing polyglutamine aggregation in disease. These results support a
      central role for protein misfolding in the pathogenesis of SCA3/MJD and suggest
      that modulating proteasome activity is a potential approach to altering the
      progression of this and other polyglutamine diseases.

PMID- 10072438
TI  - Two novel genes in the center of the 11p15 imprinted domain escape genomic
      imprinting.
AB  - We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal
      transferable fragment (STF) from human chromosome 11p15 and the identification of
      nine known genes and four novel genes within this STF. We now report the
      isolation of two novel cDNAs, designated here as TSSC4 and TSSC6 (tumor
      suppressing STF cDNA 4 and 6), located within the STF. TSSC4 and TSSC6 encode
      predicted proteins of 329 and 290 amino acids, respectively, with no close
      similarity to previously reported proteins. TSSC4 and TSSC6 are both located in
      the center of a 1 Mb imprinted domain, which contains the imprinted genes TSSC3,
      TSSC5, p57(KIP2), KVLQT1, ASCL2, IGF2 and H19. However, we found that neither
      TSSC4 nor TSSC6 was significantly imprinted in any of the fetal or extra
      embryonic tissues examined. Based on this result, the imprinted gene domain of
      11p15 appears to contain at least two imprinted subdomains, between which TSSC4
      and TSSC6 substantially escape imprinting, due either to lack of initial
      silencing or to an early developmental relaxation of imprinting.

PMID- 10072439
TI  - Structural and functional characterization of the mouse Sox9 promoter:
      implications for campomelic dysplasia.
AB  - Mutations in SOX9 cause campomelic dysplasia (CD), a dominant skeletal
      dysmorphology and XY sex reversal syndrome. The CD phenotype is sensitive to
      dosage and expression levels of SOX9. Sox9 is expressed during chondrocyte
      differentiation and is up-regulated in male and down-regulated in female genital
      ridges during sex differentiation. In order to study the sex- and tissue-specific
      regulation of Sox9, we have defined the transcription start site and
      characterized the mouse Sox9 promoter region. The Sox9 proximal promoter shows
      moderately high nucleotide similarity between mouse and human. Transient
      transfection experiments using various deletion constructs of the 6.8 kb upstream
      region of mouse Sox9 fused to a luciferase reporter showed that the interval
      between 193 and 73 bp from the transcription start site is essential for maximal
      promoter activity in cell lines and in primary male and female gonadal somatic
      cells and liver cells isolated from 13.5 d.p.c. mouse embryos. This minimal
      promoter region was shown by DNase I hypersensitive site assay to be in an 'open'
      state of chromatin structure in gonads of both sexes, but not in the liver.
      Promoter activity was higher in testis than in ovary and liver, but deletion of
      the region from -193 to -73 bp abolished this difference. We conclude that the
      proximal promoter region is in part responsible for the sex- and tissue-specific
      expression of the Sox9 gene and that more distal positive and negative elements
      contribute to its regulation in vivo, consistent with the observation that
      translocations upstream from SOX9 can result in campomelic dysplasia.

PMID- 10072440
TI  - Isolation and embryonic expression of the novel mouse gene Hic1, the homologue of
      HIC1, a candidate gene for the Miller-Dieker syndrome.
AB  - The human gene HIC1 (hypermethylated in cancer) maps to chromosome 17p13.3 and is
      deleted in the contiguous gene disorder Miller-Dieker syndrome (MDS) [Makos-Wales
      et al. (1995) Nature Med., 1, 570-577; Chong et al. (1996) Genome Res., 6, 735
      741]. We isolated the murine homologue Hic1, encoding a zinc-finger protein with
      a poxvirus and zinc-finger (POZ) domain and mapped it to mouse chromosome 11 in a
      region exhibiting conserved synteny to human chromosome 17. Comparison of genomic
      and cDNA sequences predicts two exons for the murine Hic1. The second exon
      exhibits 88% identity to the human HIC1 on DNA level. During embryonic
      development, Hic1 is expressed in mesenchymes of the sclerotomes, lateral body
      wall, limb and cranio-facial regions embedding the outgrowing peripheral nerves
      during their differentiation. During fetal development, Hic1 additionally is
      expressed in mesenchymes apposed to precartilaginous condensations, at many
      interfaces to budding epithelia of inner organs, and weakly in muscles. We
      observed activation of Hic1 expression in the embryonic anlagen of many tissues
      displaying anomalies in MDS patients. Besides lissencephaly, MDS patients exhibit
      facial dysmorphism and frequently additional birth defects, e.g. anomalies of the
      heart, kidney, gastrointestinal tract and the limbs (OMIM 247200). Thus, HIC1
      activity may correlate with the defective development of the nose, jaws,
      extremities, gastrointestinal tract and kidney in MDS patients.

PMID- 10072441
TI  - Association of an extended haplotype in the tau gene with progressive
      supranuclear palsy.
AB  - We describe two extended haplotypes that cover the human tau gene. In a total of
      approximately 200 unrelated caucasian individuals there is complete
      disequilibrium between polymorphisms which span the gene (which covers
      approximately 100 kb of DNA). This suggests that the establishment of the two
      haplotypes was an ancient event and either that recombination is suppressed in
      this region, or that recombinant genes are selected against. Furthermore, we show
      that the more common haplotype (H1) is significantly over-represented in patients
      with progressive supranuclear palsy (PSP), extending earlier reports of an
      association between an intronic dinucleotide polymorphism and PSP.

PMID- 10072442
TI  - Strategies for improving responses to DNA vaccines.

PMID- 10072444
TI  - Systemic interferon-alpha (IFN-alpha) treatment leads to Stat3 inactivation in
      melanoma precursor lesions.
AB  - BACKGROUND: In the setting of familial melanoma, the presence of atypical nevi,
      which are the precursors of melanoma, is associated with a nearly 100% risk of
      developing primary melanoma by age 70. In patients with sporadic melanoma, it is
      estimated that 40-60% of melanomas develop in contiguous association with
      atypical nevi. Currently, the only way to prevent atypical nevi from progressing
      to melanoma is to monitor and excise them as soon as they exhibit changes in
      their clinical features. Activation of the transcription factor, Stat3, has been
      linked to abnormal cell growth and transformation as well as to interferon alpha
      (IFN-alpha)-mediated growth suppression in vitro. MATERIALS AND METHODS: To
      determine whether IFN-alpha, used for adjuvant therapy of high-risk, resected
      melanoma, induces changes in Stat3 in atypical nevi, patients with a clinical
      history of melanoma who have multiple atypical nevi were treated for 3 months
      with low-dose IFN-alpha. Thereupon, the new technology of microscopic spectral
      imaging and biochemical assays such as electrophoretic mobility shift assays
      (EMSAs) and immunoblot analysis were used for the study of atypical nevi,
      obtained before and after IFN-alpha treatment. RESULTS: The results of the
      investigations provided evidence that, as a result of systemic IFN-alpha
      treatment, Stat1 and Stat3, which are constitutively activated in melanoma
      precursor lesions, lose their ability to bind DNA, and as shown in the case of
      Stat3, become dephosphorylated. CONCLUSIONS: Unlike primary and metastatic
      melanomas, melanoma precursor lesions cannot be established as cell cultures.
      Thus, the only way to explore pathways and treatment regimens that might help
      prevent progression to melanoma is within the context of a melanoma precursor
      lesion study conducted prospectively. The findings presented here suggest that
      down-regulation of the transcription factors Stat1 and Stat3 by systemic IFN
      alpha treatment may represent a potential pathway to prevent the activation of
      gene(s) whose expression may be required for atypical nevus cells to progress to
      melanoma.

PMID- 10072445
TI  - Ubiquitous induction of p53 in tumor cells by antisense inhibition of MDM2
      expression.
AB  - BACKGROUND: The MDM2 oncogene functions as a negative feedback regulator of the
      p53 tumor suppressor. Abnormal expression of MDM2 in tumors may attenuate the p53
      mediated growth arrest and apoptosis response, resulting in increased cell
      proliferation and resistance to chemotherapy. MATERIALS AND METHODS: We have
      developed phosphorothioate antisense oligodeoxynucleotides optimized for
      inhibition of MDM2 expression and investigated the role of MDM2 in a large panel
      of tumor cell lines. RESULTS: Inhibition of MDM2 expression in 15 tumor types
      containing wild-type p53 results in a significant induction of nuclear p53
      accumulation. The increase in p53 level is due to prolonged half-life and is
      associated with an increase in p53 transcriptional activity, growth inhibition,
      or apoptosis. Inhibition of MDM2 expression is also sufficient to induce nuclear
      p53 accumulation in several cell lines with cytoplasmic p53. CONCLUSIONS: The
      MDM2 negative feedback loop is important for maintenance of p53 at a low level by
      promoting p53 degradation. Nuclear export and degradation by MDM2 may contribute
      to the p53 nuclear exclusion phenotype. Inhibition of MDM2 expression can
      effectively activate p53 in most tumor types, including those without MDM2
      overexpression, and may have broad anti-tumor potential.

PMID- 10072446
TI  - Two neutralizing human anti-RSV antibodies: cloning, expression, and
      characterization.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection is a major problem in the
      newborn and aging populations. Fully human monoclonal antibodies with the ability
      to neutralize RSV could have a major impact on the immunotherapy of the disease.
      The generation of human antibodies has been difficult because there exists no
      general way to activate B cells against an antigen of choice in vitro. MATERIALS
      AND METHODS: Human spleen cells from individuals exposed to RSV were used to
      repopulate SCID mice. Hu-SCID mice were boosted with RSV fusion (F)-protein and
      subsequently developed B cell tumors. The tumors were removed and cultured and
      subcloned in vitro, using a feeder layer of CD154-expressing T cells. Two of
      these tumors produced the antibodies designated RF-1 and RF-2. VL genes were
      isolated by standard PCR techniques, however, it was necessary to use high
      temperature reverse transcriptase to clone the VH genes. RESULTS: RF-1 and RF-2
      VH genes were both found to be closely related members of the VH2 family. Vk
      genes originated from the VK III family. RF-1 and RF-2 recombinant antibodies
      expressed in CHO cells (cRF-1 and cRF-2) were found to have affinities for RSV F
      protein of 0.1 nM and 0.07 nM, respectively, and both were able to neutralize
      several A and B subtypes of RSV. CONCLUSION: The technique of immortalizing human
      B lymphocytes, by passage in SCID mice and expression as recombinant antibodies
      in CHO cells, provides a method by which high-affinity human antibodies can be
      developed for immunotherapy of viral diseases.

PMID- 10072447
TI  - Interaction of Borrelia burgdorferi with peripheral blood fibrocytes, antigen
      presenting cells with the potential for connective tissue targeting.
AB  - BACKGROUND: Borrelia Burgdorferi has a predilection for collagenous tissue and
      can interact with fibronectin and cellular collagens. While the molecular
      mechanisms of how B. burgdorferi targets connective tissues and causes arthritis
      are not understood, the spirochetes can bind to a number of different cell types,
      including fibroblasts. A novel circulating fibroblast-like cell called the
      peripheral blood fibrocyte has recently been described. Fibrocytes express
      collagen types I and III as well as fibronectin. Besides playing a role in wound
      healing, fibrocytes have the potential to target to connective tissue and the
      functional capacity to recruit, activate, and present antigen to CD4(+) T cells.
      MATERIALS AND METHODS: Rhesus monkey fibrocytes were isolated and characterized
      by flow cytometry. B. burgdorferi were incubated with human or monkey fibrocyte
      cultures in vitro and the cellular interactions analyzed by light and electron
      microscopy. The two strains of B. burgdorferi studied included JD1, which is
      highly pathogenic for monkeys, and M297, which lacks the cell surface OspA and
      OspB proteins. RESULTS: In this study, we demonstrate that B. burgdorferi binds
      to both human and monkey (rhesus) fibrocytes in vitro. This process does not
      require OspA or OspB. In addition, the spirochetes are not phagocytosed but are
      taken into deep recesses of the cell membrane, a process that may protect them
      from the immune system. CONCLUSIONS: This interaction between B. burgdorferi and
      peripheral blood fibrocytes provides a potential explanation for the targeting of
      spirochetes to joint connective tissue and may contribute to the inflammatory
      process in Lyme arthritis.

PMID- 10072448
TI  - Presence of P210bcrabl is associated with decreased expression of a beta
      chemokine C10 gene in a P210bcrabl-positive myeloid leukemia cell line.
AB  - BACKGROUND: Chronic myelogenous leukemia (CML) is thought to start with the
      acquisition of the t(9;22) chromosomal translocation that codes for the
      P210bcrabl tyrosine-specific protein kinase. The CML cells exhibit anchorage
      independent cell growth and genetic instability. After the initial phase, the
      cells acquire the phenotype of growth factor-independent growth. After the
      chronic phase, the disease evolves into the accelerated and blastic phases
      through the process of sequential random mutation. MATERIALS AND METHODS: To
      identify some of the genetic changes that contribute to the phenotype of blastic
      and accelerated phase cells, we used differential display PCR to compare levels
      of cDNA reverse transcripts of mRNA in 32Dc13 cells and 32Dc13 cells that were
      stably transfected with a bcrabl cDNA plasmid in a constitutively expressed
      transcription unit. These cells were designated 32Dc13P210bcrabl. For these
      studies, we used the 32D myeloid leukemia cell line, which depends on IL-3 for
      growth. RESULTS: Following introduction of the bcr-abl cDNA through transfection,
      the cell line became growth factor independent, mimicking the change in phenotype
      that occurs during the later phases of CML. These differential display screening
      assays detected altered levels of transcripts for 28 genes. Of interest to the
      biology of growth factor-independent growth in the bcrabl-positive 32D cells was
      the fact that the C10 beta chemokine gene was expressed at higher levels in the
      32Dc13 cells than in the 32Dc13P210bcrabl cells. CONCLUSIONS: These studies show
      that a C10 beta chemokine gene was expressed at different levels with or without
      P210bcrabl.

PMID- 10072450
TI  - Endovascular stent-graft treatment of traumatic arterial lesions.
AB  - Twenty-nine cases of post-traumatic false aneurysms and arteriovenous fistulas
      (AVF), with a mean follow-up of 24 months (1-65 months), are presented here.
      Diagnosis was established by color duplex and arteriogram. The time between
      injury and treatment varied between 3 days and 61 months. Endovascular treatment
      was accomplished using a covered Palmaz stent [vein, polytetrafluoroethylene
      (PTFE), or polyester], Corvita endoluminal graft, or a Wallgraft. Complimentary
      treatment of a branch injury was performed using a detachable balloon in one
      patient. The initial result was favorable for all patients. One case of
      asymptomatic stenosis of an iliac stent graft and three occlusions of the stent
      (one subclavian, one axillary, and one internal carotid) were registered during
      the follow-up period, and no clinical manifestations of the occlusions were
      reported. Endovascular treatment of post-traumatic false aneurysms and AVF
      appears to be a promising alternative for treatment of these lesions. Less pain
      and disability as well as rapid recovery time and lower cost after endovascular
      treatment compare favorably to the standard surgical technique.

PMID- 10072451
TI  - Comparison of healing in fresh and preserved arterial allografts in the dog.
AB  - The use of aortic allografts for the management of vascular prosthetic infections
      has recently been reintroduced. Impressive results have been obtained; however,
      the possibility of late degeneration remains a major concern. The healing
      behavior of aortic allografts, either fresh or preserved, in antibiotic
      supplemented nutrient medium at 4 degrees C for 1 week and used as thoracic aorta
      substitutes in dogs was investigated after 6 months of implantation. Four dogs
      received a fresh aortic allograft from four different donors, and four dogs
      received a preserved allograft from two different donors. Autografts in two dogs
      were performed as controls. The in vivo investigation was conducted to describe
      (1) the histological characteristics of the arterial wall, (2) the macroscopic
      and thrombogenic aspect of the luminal surface, (3) the integrity of the
      endothelial lining by scanning electron microscopy, and (4) its biochemical
      function by prostacyclin (PGI2) and thromboxane A2 (TXA2) secretion. Immune
      mediated reactions directed toward the grafts were measured by sequential
      screening of donor-specific serum antibody development. All donor-recipient pairs
      of dogs were major histocompatibility complex (MHC)-incompatible according to a
      mixed lymphocyte reaction (MLR) assay. From the results of this study we
      concluded that although preserved arterial allografts exhibited similar surface
      characteristics as those of fresh allografts in terms of re-endothelialization
      and long-term graft function, an elicited immune response, a degenerative process
      in the media, and a hyperplasic reaction in the intima could not be prevented
      using this method of preservation.

PMID- 10072452
TI  - In vitro endothelialization of PTFE vascular grafts: A comparison of various
      substrates, cell densities, and incubation times.
AB  - To establish the optimal conditions for achieving endothelial cell coverage of
      the luminal surfaces of small-caliber vascular grafts in vitro, the attachment of
      endothelial cells (ECs) cultured from human umbilical veins to
      polytetrafluoroethylene (PTFE) grafts was studied. Cell attachment and spreading
      were compared after PTFE grafts were (a) precoated with fibronectin (HFN), type I
      collagen, type IV collagen, plasma and fibrin with or without thrombin, singly or
      in combination; (b) seeded with cell densities varying from 0.5 x 10(5) to 6 x
      10(5) cells/cm2; and (c) incubated at 30, 60, or 90 min. Cell coverage and
      spreading were assessed by means of scanning electron microscopy. Quantification
      of graft surface coverage was performed with computer-assisted image analysis. To
      determine optimal conditions of endothelialization among the 189 treatment
      combinations, analysis of variance was used. We conclude that a virtually
      confluent cell monolayer can be established on small-caliber PTFE grafts when
      precoated with fibrin glue or plasma, seeded with cell densities >/=4 x 10(5)
      cells/cm2, and incubated for 60 min. These parameters are compatible with an
      operating room vascular procedure.

PMID- 10072453
TI  - Early experience with the Corvita endoluminal graft for treatment of arterial
      injuries.
AB  - The aim of this study was to evaluate our early experience with the Corvita
      endoluminal graft for the treatment of a variety of arterial injuries. Ten
      patients with arterial pseudoaneurysms (8) or arteriovenous fistulas (2) due to
      arterial injuries were followed prospectively after undergoing treatment with the
      endovascular graft. Our results showed that the Corvita low-profile endoluminal
      graft can be successfully used to treat arterial injuries but that it sometimes
      requires the placement of additional stents in patients with tortuous or tapering
      vessels. These grafts are extremely useful for the safe treatment of difficult
      and high-risk patients. Further improvements in available endovascular grafts and
      good long-term results will be necessary before considering these grafts the best
      treatment available for most patients with significant arterial injuries.

PMID- 10072454
TI  - Carotid endarterectomy in symptomatic and asymptomatic patients aged 75 years or
      more: perioperative mortality and stroke risk rates.
AB  - The aim of this retrospective study was to determine whether age per se
      constitutes a contraindication to surgery in the elderly patient undergoing
      carotid endarterectomy (CEA) with regard to operative mortality and stroke risk
      morbidity. During an 8-year period, 96 patients aged 75 years or more underwent
      103 CEAs. The age range was 75 to 89 years, with a median age of 79 and a mean
      age of 79.4 years. Fifty-nine CEAs with patch closure and 44 carotid eversion
      endarterectomies and reimplantation were performed for symptomatic (70.9%) and
      asymptomatic (29.1%) carotid lesions under general anesthesia and with continuous
      perioperative electroencephalographic (EEG) monitoring. In light of the efficacy
      and success achieved in this experience, advanced age does not seem in itself to
      contraindicate the performance of CEA; the surgical risk for elderly patients
      appears sufficiently low to justify the operation. A more aggressive approach may
      be warranted in elderly patients because of the morbidity and cost of the disease
      that it effectively prevents.

PMID- 10072455
TI  - Carotid screening with duplex ultrasound in elderly asymptomatic patients
      referred to a vascular surgeon: is it worthwhile?
AB  - The purpose of this study is to prospectively determine the outcome of carotid
      duplex ultrasound screening in patients referred to a vascular surgeon for
      problems other than carotid disease. During a recent 12-month period, 307
      patients age 65 years and older (mean 76 +/- 8 years) were referred to one
      vascular surgeon for problems other than cerebrovascular disease. Fifty-one
      percent of the patients were male, 49% were female, 32% were diabetic, 32% were
      hypertensive, 31% smoked, 20% had coronary artery disease, and 64% had peripheral
      arterial occlusive disease. All patients underwent a screening duplex ultrasound
      exam of the carotid arteries as approved by our Institutional Review Board. The
      results of our study showed that the prevalence of asymptomatic carotid artery
      stenosis >70% among patients seen by a vascular surgeon for problems other than
      cerebrovascular disease is high (21%) and is associated with male gender,
      advanced age, diabetes mellitus and having quit smoking. Continued carotid artery
      duplex screening is warranted in this patient population greater than age 65
      years.

PMID- 10072456
TI  - The role of patch angioplasty in prevention of early recurrent carotid stenosis.
AB  - The aim of this study was to determine the effect of primary closure versus patch
      angioplasty on the incidence of early recurrent stenosis after carotid
      endarterectomy in the hands of a single surgeon, and to analyze the risk factors
      associated with early recurrent stenosis after carotid endarterectomy. A
      retrospective review was performed of 178 consecutive patients who underwent 200
      carotid endarterectomies-100 done consecutively with primary closure and 100 done
      consecutively with patch angioplasty. Of these patients, 126 qualified for
      analysis by having had at least 18 months of follow-up by serial duplex scanning.
      Of this group, the first 65 patients underwent 75 routine primary closures, while
      the last 61 underwent 67 routine patch angioplasties. All patients underwent a
      completion angiogram at the end of the case. Recurrent stenosis was defined as
      luminal diameter narrowing >60% on duplex scan. A multifactorial analysis was
      performed to analyze the effect of age, sex, tobacco use, diabetes, hypertension,
      peripheral vascular disease, coronary artery disease, and contralateral stenosis
      on recurrent stenosis. The results of this study showed that in a single
      surgeon's experience with carotid endarterectomy, varying only the method of
      closure between primary closure versus patch angioplasty, there is no
      statistically significant difference in the rate of early restenosis. No
      difference was noted in the perioperative morbidity and mortality between groups.

PMID- 10072457
TI  - Fifteen years with the Southern California Vascular Surgical Society.
AB  - A brief history of the Southern California Vascular Surgical Society was
      presented at its sixteenth meeting. This review includes an account of the
      proliferation of vascular societies in the last 50 years as well as the specifics
      of the circumstances surrounding this society's origin and its close relationship
      with the Annals of Vascular Surgery. A review of the course of the society notes
      the common pattern of distinguished guests and of socioeconomic presentations
      that have become so important during these last 15 years.

PMID- 10072458
TI  - Improved imaging of carotid artery bifurcation using helical computed tomographic
      angiography.
AB  - Although duplex scan and magnetic resonance angiography (MRA) provide reliable
      and noninvasive tests for detecting extracranial carotid artery disease, they
      sometimes fail to differentiate between high-grade stenosis and total carotid
      occlusion. Helical computed tomographic angiography (CTA) is a safe, noninvasive
      technique that allows the rapid acquisition of data that can be reconstructed
      into two- and three-dimensional images. Axial images can be magnified and provide
      a cross-sectional view of the carotid vessel and the atherosclerotic plaque.
      Maximal intensity projection technique allows data to be reconstructed into
      images that closely resemble conventional arteriograms. Helical CTA has
      previously been shown to have a diagnostic accuracy approaching 90%. We present
      two case reports demonstrating the utility of helical CTA in carotid artery
      imaging when duplex scan and MRA results are ambiguous. These cases illustrate
      improved carotid imaging with helical CTA. Duplex scan results are unreliable in
      the presence of thick calcified plaques, and severe stenoses can be misread as
      occlusion by duplex and MRA due to low blood flow. Thus, helical CT angiography
      should be considered as a confirmatory test, before arteriography, when duplex
      scan or MRA results are equivocal.

PMID- 10072459
TI  - Percutaneous transluminal angioplasty of infrainguinal vessels.
AB  - In the last decade, percutaneous angioplasty (PTA) has been used with increasing
      frequency to treat infrainguinal atherosclerotic lesions. In hopes of better
      delineating the role of PTA, we undertook a retrospective analysis of
      infrainguinal PTA in one hospital over a 7-year period. The charts of all
      patients receiving infrainguinal PTA from 1989 to 1996 were reviewed.
      Demographics, site and type of lesion, and results of treatment were recorded.
      Survival curves were plotted using the Kaplan-Meier method following current
      Society of Vascular Surgery/International Society for Cardiovascular Surgery
      (SVS/ISCVS) guidelines. Differences in times to first failure were tested using
      the log rank method. Failures were documented by duplex ultrasound. All patients
      requiring repeat intervention underwent contrast angiography. In selected
      patients with stenotic lesions <3 cm, infrainguinal PTA may be an appropriate
      initial treatment modality. However, 5-year patency rates are significantly lower
      than those achieved by saphenous vein grafting. The efficacy of the procedure is
      markedly decreased when used to treat arterial stenoses >3 cm in length as well
      as occlusions, and surgical revascularization may be a more appropriate initial
      therapeutic procedure.

PMID- 10072460
TI  - Mycotic aneurysms of the tibioperoneal arteries.
AB  - This case report describes a pediatric patient with mycotic aneurysms of both
      posterior tibial arteries and the right peroneal artery associated with an
      episode of endocarditis. To our knowledge, this case represents the first
      reported occurrence of multiple mycotic aneurysms of the tibioperoneal arteries.
      It is also unique in that the pathogen was Brucella canis instead of the usual
      gram-positive pathogens associated with intravenous drug injection. Vascular
      reconstruction can be accomplished; however, management of this complex problem
      should be individualized.

PMID- 10072461
TI  - A prospective evaluation of PTFE graft patency and surveillance techniques in
      hemodialysis access.
AB  - The purpose of this study was to perform a prospective multicenter evaluation of
      the patency, complications, and predictive factors of patency for 6-mm expanded
      polytetrafluoroethylene (ePTFE) grafts used in hemodialysis access. Eighty-six
      patients were evaluated; the mean age was 55.8 years (range 23-90), 46 patients
      were female. Patency and complications were assessed at the initial dialysis and
      1, 3, 6, 9, and 12 months postoperatively. Kaplan-Meier survival curves were
      calculated to determine primary and secondary patency, and log-rank analysis was
      used to determine differences between curves. The Student's t-test was used to
      compare groups. Primary and secondary patency rates at 1 year were 43% and 64%.
      Venous line pressures tended to rise over time. Recirculation values and blood
      flow rates during dialysis showed no correlation to graft patency. These results
      show that ePTFE provides a suitable secondary choice for vascular access for end
      stage renal disease patients in whom an autogenous fistula is not possible.
      Thrombosis and anastomotic stenosis are common and should be aggressively
      identified and treated to prolong overall graft survival.

PMID- 10072462
TI  - Abdominal aortic aneurysm repair in patients with renal allografts.
AB  - Aortic reconstruction is being reported in an increasing number of patients after
      renal transplantation as a result of improved renal graft survival and life
      expectancy. Aortic surgery in these patients places the pelvic allograft at risk
      for ischemic damage. We present two separate modalities that have been
      successfully used in protecting the renal transplant from prolonged warm ischemia
      during abdominal aortic aneurysm (AAA) repair in two cases. One technique
      involves an aortofemoral shunt using the perirenal aorta for proximal cannulation
      and the other technique utilizes an indwelling shunt through the prosthetic
      graft. Both patients had an uneventful recovery with no evidence of renal
      dysfunction and their renal function has been stable on long-term follow-up.
      These cases illustrate two useful alternatives in providing pulsatile perfusion
      to a transplanted kidney in the iliac fossa during AAA repair. They have been
      used successfully as simpler alternatives to temporary axillofemoral bypass or
      extracorporeal pump oxygenation in preventing postoperative renal dysfunction.

PMID- 10072463
TI  - Cardiac morbidity and operative mortality following lower-extremity amputation:
      the significance of multiple Eagle criteria.
AB  - The ability of the Eagle criteria (age >70 years, angina, diabetes, Q wave on
      EKG, history of congestive heart failure) to predict adverse cardiac events
      following major vascular surgery has previously been demonstrated. However, the
      utility of these criteria for lower-extremity amputation is not well established.
      To determine the value of the Eagle criteria for predicting cardiac morbidity and
      operative mortality following major lower-extremity amputation, we reviewed 214
      consecutive procedures performed at two institutions over a 3-year period. Mean
      age was 62.7 years and 85% of the patients were male. Diabetes was the most
      frequent Eagle criterion (74%). The mean number of Eagle criteria was 1.6. Fifty
      six percent of the amputations were below the knee, 24% were above the knee, and
      20% were guillotine. On multivariate regression analysis, the presence of two or
      more Eagle criteria (16% vs. 4%, p = 0.04) and decompensated heart failure (39%
      vs. 7%, p = 0.003) were predictive of adverse cardiac events. The only predictor
      of postoperative mortality was the presence of two or more Eagle criteria (15%
      vs. 4%, p = 0.004). Our evaluation of the results of this study led us to
      conclude that patients requiring major lower-extremity amputation for major
      vascular disease who have multiple Eagle criteria or decompensated congestive
      heart failure are at high risk for adverse cardiac events and postoperative
      death. These findings should be used to guide perioperative cardiac evaluation
      and therapy.

PMID- 10072464
TI  - Iliac to popliteal artery bypass through the iliac wing: An alternative
      extracavitary route for management of complex groin injuries.
AB  - Extracavitary bypass through the iliac wing allows placement of the grafts into
      the posterior thigh and is another alternative route when an obturator bypass is
      not possible, or an axillary-popliteal bypass is to be avoided. The transiliac
      wing bypass is relatively simple and easy to perform. The bypass route is short
      and direct, has excellent inflow, and is accompanied by minimal neurological or
      bleeding risks. An illustrative case is presented with a complete description of
      the operative technique. Review of the literature is also included.

PMID- 10072465
TI  - Thoracoabdominal aortic aneurysm repair with sequential visceral perfusion: A
      technical note.
AB  - The aim of this study was to develop a method for type III and type IV
      thoracoabdominal aortic aneurysm (TAA) repair that reduces ischemia time to the
      abdominal viscera, spinal cord, and lower extremities. Over a 25-month period,
      five type IV TAAs and three type III TAAs were repaired with a trifurcated
      polytetrafluoroethylene (PTFE) graft to bypass three of four visceral vessels and
      another graft to reconstruct the thoracoabdominal aorta. The trifurcated graft
      was sewn end-to-side to an unaffected area of descending thoracic aorta.
      Sequential end-to-end bypasses to the left renal, superior mesenteric, and celiac
      arteries followed this anastomosis. The remaining TAA was then replaced with a
      Dacron tube or bifurcated graft by clamping distal to the trifurcated graft so as
      to maintain visceral and left renal artery perfusion. Implantation of the right
      renal artery into the Dacron graft completed visceral artery reconstruction. The
      postoperative results indicate the feasibility of type III and IV TAA repair
      using tangential thoracic aortic clamping, individual aortic branch vessel
      reconstruction, and separate distal revascularization. This operative technique
      decreases ischemia time to the abdominal viscera, spinal cord, and lower
      extremities.

PMID- 10072466
TI  - Inflammatory abdominal aortic aneurysm and bilateral complete ureteral
      obstruction: treatment by endovascular graft and bilateral ureteric stenting.
AB  - Inflammatory abdominal aortic aneurysms may present a challenge to the surgeon,
      especially because of associated retroperitoneal fibrosis and possible ureteral
      complications. We present a case of inflammatory abdominal aortic aneurysm with
      bilateral ureteral entrapment and complete anuria, successfully treated by
      endovascular grafting and temporary ureteral stenting.

PMID- 10072467
TI  - In situ repair of a secondary aortoappendiceal fistula with a rifampin-bonded
      Dacron graft.
AB  - Secondary aortoenteric fistulas remain challenging diagnostic and therapeutic
      problems. Although the duodenum is most frequently involved, other intestinal
      segments are possible sites for fistulization. We report here a case of graft
      appendiceal fistula revealed by recurrent gastrointestinal bleeding 11 years
      after abdominal aortic aneurysm replacement. The preoperative diagnosis was not
      achieved by endoscopy or imaging assessment. Despite recommended principles of
      total graft excision and extraanatomic bypass, appendectomy and in situ rifampin
      bonded graft reconstruction were performed because of the advanced age and poor
      arterial runoff. The postoperative course was uneventful and the patient remains
      well 17 months after operation.

PMID- 10072468
TI  - Spontaneously developed aneurysm of the ductus arteriosus in an adult.
AB  - We report an unusual adult case of aneurysm associated with the ductus
      arteriosus. A 67-year-old female, who suffered recurrent nerve palsy, was
      diagnosed as having an aneurysm of the ductus arteriosus. The aneurysm, located
      in the medial aspect of the aortic ischimus and projected toward the pulmonary
      artery, was successfully repaired using a Dacron patch. A pathologic review of
      the aneurysm revealed the degeneration of the aortic media.

PMID- 10072469
TI  - Frey's syndrome after carotid endarterectomy.
AB  - Frey's syndrome after carotid endarterectomy (CEA) is due to iatrogenic injury to
      the auriculotemporal nerve and has not been previously reported. One month after
      uncomplicated CEA, our patient noted an erythematous flush and copious drainage
      of clear fluid from the superior portion of his neck wound whenever he ate, or
      smelled or thought of food. These symptoms lasted for 2 months and eventually
      resolved without intervention. The cause and treatment of Frey's syndrome is also
      described.

PMID- 10072470
TI  - Surgical treatment of patients with symptomatic vertebrobasilar insufficiency.

PMID- 10072471
TI  - Expression of matrix metalloproteinases and TIMPs in human abdominal aortic
      aneurysms.

PMID- 10072472
TI  - The transference of results between blood-brain barrier cell culture systems.

PMID- 10072473
TI  - Metabolism of the stable nitroxyl radical 4-oxo-2,2,6, 6-tetramethylpiperidine-N
      oxyl (TEMPONE).
AB  - The formation of new metabolites of the stable nitroxyl radical 4-oxo-2,2,6,6
      tetramethylpiperidine-N-oxyl (TEMPONE) inside the isolated perfused rat liver was
      examined. The paramagnetic 4-hydroxy derivative (TEMPOL) and the diamagnetic 1,4
      dihydroxy derivative were found to be the major metabolites besides the well
      known corresponding hydroxylamine of TEMPONE. No reoxidation of the hydroxyl
      group in the 4-position was observed. The conversion of nitroxides to the
      sterically hindered secondary amines remains speculative. A redox cycle of
      nitroxide and hydroxylamine including the secondary amines is discussed. For the
      first time the biotransformation of the stable nitroxyl radical TEMPONE detected
      by means of GC and GC-MS has been examined and new metabolites have been
      described, i.e. the newly discussed metabolites have to be considered for the
      interpretation of electron paramagnetic resonance (EPR), magnetic resonance
      imaging (MRI) and dynamic nuclear polarization (DNP) measurements on using the
      spin probe TEMPONE.

PMID- 10072474
TI  - Tabletting behaviour of pellets of a series of porosities--a comparisonbetween
      pellets of two different compositions.
AB  - The tabletting behaviour of pellets prepared from a 4:1 mixture of dicalcium
      phosphate dihydrate (DCP) and microcrystalline cellulose (MCC) was studied and
      compared with the tabletting behaviour of pellets made solely from
      microcrystalline cellulose (results from an earlier study by Johansson et al.). A
      series of pellets with porosities in the range 26-55% were prepared and tabletted
      at applied pressures of 25-200 MPa. Tablets were also formed from lubricated
      pellets. The degree of compression during compaction was calculated, and the
      porosity and tensile strength of the tablets and their permeability to air flow
      were determined. The porosity of the pellets was found to significantly affect
      the tabletting behaviour of the DCP/MCC pellets. However, the relationship
      between pellet porosity and tablet data for the DCP/MCC pellets was different
      from that for the MCC pellets. The DCP/MCC pellets were generally less prone to a
      reduction in volume during tabletting, and the pore structure of the DCP/MCC
      tablets was more closed. It was concluded that the DCP/MCC pellets were more
      rigid and underwent a different mode of deformation during tabletting than the
      MCC pellets. This mode of deformation was characterised by a more limited bulk
      deformation and a more extensive surface deformation at the pellet surfaces. The
      DCP/MCC pellets tended to give tablets of a lower mechanical strength. They were
      also less sensitive to lubrication in terms of their compactability, which may be
      explained either by less surface coverage by the lubricant before compression or
      rupture of the lubricant film during compression caused by the more extensive
      surface deformation of DCP/MCC pellets.

PMID- 10072475
TI  - A comparison between direct determination of in vivo dissolution and the
      deconvolution technique in humans.
AB  - AIM: The primary objective of this study was to investigate the in vivo
      dissolution of carbamazepine in humans and to compare it with the dissolution
      estimated by deconvolution of plasma concentrations as well as the in vitro
      dissolution. METHODS: The in vivo study included six healthy volunteers, and
      consisted of two sequential parts. In part 1 the dissolution was measured by
      perfusing a semi-open segment in the proximal jejunum in humans. In part 2 the
      volunteers were given a solution of carbamazepine orally. In both parts of the
      study, plasma samples were collected up to 48 h after administration of the dose.
      The in vitro dissolution was measured in a flow-through cell using dissolution
      medium with and without the addition of bile acids (3 mM). RESULTS: The direct
      measured in vivo dissolution profile of carbamazepine and the deconvoluted
      profile were found to be similar. The two dissolution profiles of carbamazepine
      obtained in vitro were statistically lower than the two in vivo dissolution
      profiles. The higher in vivo dissolution rate is probably due to efficient sink
      conditions as a consequence of the high permeability of carbamazepine and more
      pronounced intestinal motility. CONCLUSION: The jejunal perfusion system was
      successfully used for in vivo dissolution measurements of carbamazepine and
      agreed with the deconvoluted plasma profile regarding rate and extent of
      dissolution. Single-pass perfusion is therefore a meaningful tool for further
      studies of in vivo dissolution.

PMID- 10072477
TI  - M3/M1-Selective antimuscarinic tropinyl and piperidinyl esters.
AB  - The binding affinities of some tropinyl and piperidinyl esters for the
      submandibulary glands (M3/M1) and heart ventricle (M2) were determined from
      displacement experiments using 3H-labelled N-methylscopolamine as radioligand.
      The antimuscarinic activities of these esters were also evaluated on guinea pig
      bronchi. The esters inhibited the M3-mediated carbachol-induced contraction of
      the bronchial smooth muscle and a reasonable correlation was obtained between the
      binding affinities of the esters for the submandibulary glands (pKM3,M1) and
      their inhibitory activities (pIC50) on guinea pig bronchi. A promising compound,
      N-methylpiperidinyl cyclohexylphenylpropionate (NCPP) which combined good
      antimuscarinic activity (pA2=9.34) with a 20-fold selectivity at the M3/M1
      receptors, was identified. Quantitative structure-activity relationships (QSAR)
      showed that the size of the ester was the main structural feature determining
      both binding affinity for the M3/M1 receptors and inhibitory activity on guinea
      pig bronchi. Esters with substituted acyl side chains (fewer hyperconjugable H
      atoms at the alpha-carbon) are generally associated with better activity and
      affinity.

PMID- 10072476
TI  - In vitro hydrolysis rate and protein binding of clevidipine, a new ultrashort
      acting calcium antagonist metabolised by esterases, in different animal species
      and man.
AB  - The objectives of this study were to investigate the protein binding and the in
      vitro hydrolysis rate of clevidipine and its enantiomers in the rat, dog and man
      in different biological matrices including blood and plasma from volunteers with
      deficient pseudocholinesterase activity. The in vitro half-life in blood was 0.6
      min (rat), 15.7 min (dog) and 5.8 min in man with normal pseudocholinesterase
      activity, while the half-life was approximately 9 min in blood from
      pseudocholinesterase deficient volunteers. The half-life in pseudocholinesterase
      deficient volunteers was prolonged, although the hydrolysis rates in blood and
      red blood cells (RBC) were much higher than in plasma, suggesting that esterases
      located in the RBC are most important in the blood metabolism of clevidipine. A
      decrease in temperature increased the half-life of clevidipine in blood, whereas
      dilution of the blood did not affect the in vitro half-life of clevidipine. The
      albumin concentration affected the hydrolysis rate of clevidipine in RBC
      suspended with saline. The protein binding of clevidipine and its enantiomers was
      >99.5% in plasma from all species studied. There was a difference between the
      free fractions of S- and R-clevidipine in man, 0.43 and 0.32%, respectively, and
      this stereoselective binding might be the reason for the 10% difference between
      the in vitro hydrolysis rates of the enantiomers in human blood.

PMID- 10072478
TI  - Theoretical calculation and prediction of intestinal absorption of drugs in
      humans using MolSurf parametrization and PLS statistics.
AB  - A method for modeling and prediction of the intestinal absorption of drugs in
      humans using theoretically computed molecular descriptors and multivariate
      statistics has been investigated using 20 diverse drug-like compounds. The
      program MolSurf was used to compute theoretical molecular descriptors related to
      physicochemical properties such as lipophilicity, polarity, polarizability and
      hydrogen bonding. The multivariate Partial Least Squares Projections to Latent
      Structures (PLS) method was used to delineate the relationship between the
      intestinal absorption of drugs in humans and the theoretically computed molecular
      descriptors.Good statistical models were derived. Properties associated with
      hydrogen bonding had the largest impact on absorption and should be kept to a
      minimum to promote high absorption. High charge-transfer properties and the
      presence of surface electrons, i.e. valence electrons, which are not tightly
      bonded to the molecule, were also found to promote high absorption.

PMID- 10072479
TI  - Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled
      plasma and individual data.
AB  - Thioctic acid (TA), a racemate of R-(+)- and S-(-)-enantiomers of alpha-lipoic
      acid, acts as a powerful lipophilic, free-radical scavenger and is used in the
      treatment of diabetic neuropathy. This trial investigated the dose-linearity of
      enantiomer pharmacokinetics following the oral administration of single doses of
      50 to 600 mg TA (formulation provided by ASTA (Medica)) in healthy volunteers. TA
      enantiomer concentrations in individual and pooled plasma samples were determined
      using enantioselective, high-performance liquid chromatography. TA was rapidly
      absorbed (tmax, 0.5 to 1 h). Maximum plasma concentrations (Cmax) of the R-(+)
      enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg:
      135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA,
      978.20 ng/ml S-(-)-TA; geometric means). The decline observed in the plasma
      concentration was steep (t1/2, 0.5 h). The dose-linearity and proportionality of
      pharmacokinetic parameters could be demonstrated on an intra-individual basis and
      for the group geometric means. An analysis of pooled plasma samples proved to be
      a suitable means for deriving reliable first-sight results prior to individual
      assessments.

PMID- 10072480
TI  - Stability, metabolism and transport of D-Asp(OBzl)-Ala--a model prodrug with
      affinity for the oligopeptide transporter.
AB  - The model prodrug D-Asp(OBzl)-Ala has previously been shown to have affinity and
      to be transported by the oligopeptide transporter PepT1 expressed in Caco-2
      cells. The main objective of the present study was to investigate the aqueous
      stability of D-Asp(OBzl)-Ala and its in vitro metabolism in different
      gastrointestinal media arising from rats and humans, as well as in human plasma.
      The second major aim of the study was to evaluate our previous study in Caco-2
      cell culture, by determining the effective intestinal permeability (Peff) of D
      Asp(OBzl)-Ala in situ using the single-pass rat perfusion model. The aqueous
      stability studies show water, general buffer, as well as specific acid and base
      catalysis of D-Asp(OBzl)-Ala. The degradation of the model prodrug was
      independent of ionic strength. The half-lives in rat jejunal fluid and homogenate
      were >3 h. In human gastric and intestinal fluids, the half-lives were >3 h and
      2.3+/-0. 03 h, respectively. Using the rat single-pass perfusion technique, the
      effective jejunal permeability (Peff) of D-Asp(OBzl)-Ala was determined to be
      high (1.29+/-0.5.10-4 cm/s). The 32 times higher Peff value found in the
      perfusion model compared to Caco-2 cells is most likely due to a higher
      functional expression of the oligopeptide transporter. Rat jejuna Peff was
      reduced by approximately 50% in the presence of well known oligopeptide
      transporter substrates, such as Gly-Sar and cephalexin. It may be that D
      Asp(OBzl)-Ala is primarily absorbed intact by the rat jejunal oligopeptide
      transporter, since the stability in the intestinal homogenate and fluids was
      rather high (t1/2>2.3 h).

PMID- 10072481
TI  - Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated
      cytotoxicity.
AB  - Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal
      Src and Syk family protein tyrosine kinases to downstream effectors. However, the
      mechanisms linking these second messenger pathways are incompletely understood.
      Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell
      activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through
      FcgammaRIII receptors and following direct contact with NK-sensitive target
      cells. This NK stimulation induces the association of LAT with several
      phosphotyrosine-containing proteins. In addition to the biochemical evidence
      showing LAT involvement in NK cell activation, a genetic model shows that LAT is
      required for FcR-dependent phosphorylation of phospholipase C-gamma. Furthermore,
      overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated
      cytotoxicity and "natural cytotoxicity," thus demonstrating a functional role for
      LAT in NK cells. These data suggest that LAT is an important adaptor protein for
      the regulation of human NK cell-mediated cytotoxicity.

PMID- 10072482
TI  - Cutting edge: clustered AU-rich elements are the target of IL-10-mediated mRNA
      destabilization in mouse macrophages.
AB  - In the present study we show that IL-10-mediated inhibition of inflammatory gene
      expression can be mediated by an AU-rich element (ARE) cluster present in the 3'
      untranslated region (3'UTR) of sensitive genes. A series of chloramphenicol
      acetyl transferase (CAT) reporter gene constructs were prepared in which
      different fragments from the IL-10-sensitive KC mRNA 3'UTR were placed downstream
      of the coding region of the reporter gene CAT. CAT mRNA containing the KC 3'UTR
      was markedly destabilized as compared with the control CAT mRNA, and the decay
      rate was further increased in cells stimulated with IL-10. The KC 3'UTR contains
      an ARE cluster and three isolated ARE motifs. The ARE cluster spanning
      nucleotides 378-399 appeared to be both necessary and sufficient to mediate
      sensitivity to IL-10 because a 116-nucleotide fragment that contains the cluster
      conferred sensitivity, while mutation of the sequence between positions 378 and
      399 eliminated sensitivity. The destabilizing effect of IL-10 was relatively
      selective, as the stability of chimeric CAT mRNAs was not modulated in cells
      treated with IFN-gamma or IL-4.

PMID- 10072483
TI  - Cutting edge: primary structure of the light chain of fusion regulatory protein
      1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost
      identical to the amino acid transporter E16.
AB  - The CD98 light chain (CD98LC) was copurified from HeLa S3 cells by an affinity
      chromatography using a mAb specific for the fusion regulatory protein-1 (FRP-1)
      which is identical to the CD98 heavy chain. On the basis of the N-terminal
      sequence (63 amino acids) of purified CD98LC polypeptide, we have cloned a PCR
      fragment (155 bp) from a HeLa S3 cDNA library and finally obtained a full cDNA
      clone encoding the CD98LC. Fluorescence in situ hybridization analysis using the
      cDNA assigned the CD98LC gene to the long arm of human chromosome 16 (16q24). The
      predicted amino acid sequence suggested that CD98LC is a protein with multiple
      transmembrane domains and is almost identical to the amino acid transporter E16.
      Resting monocytes and lymphocytes expressed CD98LC as analyzed by a newly
      isolated anti-CD98LC mAb, which showed cross-reactivity with insect Sf9 cells as
      well as with various mammalian cell lines.

PMID- 10072484
TI  - Cutting edge: alloimmune responses against major and minor histocompatibility
      antigens: distinct division kinetics and requirement for CD28 costimulation.
AB  - Comparative study of alloimmune responses against major and minor
      histocompatibility Ags has been limited by the lack of suitable assays. Here, we
      use a bioassay that permits tracking of alloreactive CD4+ T cell populations as
      they proliferate in response to major or minor histocompatibility Ags in vivo.
      Division of alloreactive CD4+ T cells proceeded more rapidly in response to major
      histocompatibility Ags than minor Ags, although CD4+ T cells alloreactive to
      minor Ags had a similar capacity to divide successively up to eight times after
      stimulation. Allorecognition of minor histocompatibility Ags was highly dependent
      on CD28 costimulation, with the frequency of CD4+ T cells proliferating in
      response to minor Ags in the absence of CD28 costimulation reduced up to 20-fold.
      These findings highlight differences in signaling processes that lead to
      allorecognition of major and minor histocompatibility Ags and have implications
      on the design of interventions aimed at abrogating these responses.

PMID- 10072485
TI  - Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor
      7 (CCR7) participate in the emigration pathway of mature dendritic cells from the
      skin to regional lymph nodes.
AB  - Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune
      responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine
      (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the
      chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7
      (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II
      positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC
      was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it
      enhanced the emigration of MHC class II-positive DCs from mouse skin explants by
      an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans
      cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti
      eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from
      footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct
      evidence that SLC and CCR7 participate in the emigration of DCs from peripheral
      tissue to LNs via lymphatics.

PMID- 10072486
TI  - Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently
      induces eotaxin expression by airway epithelial cells.
AB  - Airway inflammation associated with asthma is characterized by massive
      infiltration of eosinophils, mediated in part by specific chemoattractant factors
      produced in the lung. Allergen-specific Th2 cells appear to play a central role
      in asthma; for example, adoptively transferred Th2 cells induced lung
      eosinophilia associated with induction of specific chemokines. Interestingly, Th2
      supernatant alone administered intranasally to naive mice induced eotaxin,
      RANTES, monocyte-chemotactic protein-1, and KC expression along with lung
      eosinophilia. We tested the major cytokines individually and found that IL-4 and
      IL-5 induced higher levels of macrophage-inflammatory protein-1alpha and KC; IL-4
      also increased the production of monocyte-chemotactic protein-1; IL-13 and IL-4
      induced eotaxin. IL-13 was by far the most potent inducer of eotaxin; indeed, a
      neutralizing anti-IL-13 Ab removed most of the eotaxin-inducing activity from Th2
      supernatants, although it did not entirely block the recruitment of eosinophils.
      While TNF-alpha did not stimulate eotaxin production by itself, it markedly
      augmented eotaxin induction by IL-13. IL-13 was able to induce eotaxin in the
      lung of JAK3-deficient mice, suggesting that JAK3 is not required for IL-13
      signaling in airway epithelial cells; however, eosinophilia was not induced in
      this situation, suggesting that JAK3 transduces other IL-13-mediated mechanisms
      critical for eosinophil recruitment. Our study suggests that IL-13 is an
      important mediator in the pathogenesis of asthma and therefore a potential target
      for asthma therapy.

PMID- 10072487
TI  - Fas ligand-mediated exocrinopathy resembling Sjogren's syndrome in mice
      transgenic for IL-10.
AB  - Although IL-10 has been implicated in the pathogenesis of several autoimmune
      diseases, the mechanisms by which this cytokine mediates inflammatory lesions
      remain to be elucidated. Exocrine gland destruction is an important early step in
      the development of Sjogren's syndrome. To better understand the role of IL-10 in
      Sjogren's syndrome, we made transgenic mice in which the mouse IL-10 gene was
      regulated by the human salivary amylase promoter. Transgenic expression of IL-10
      induced apoptosis of glandular tissue destruction and lymphocyte infiltration
      consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up
      regulation of FasL expression on T cells. These data suggest that overexpression
      of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue
      destruction is a causal factor in the development of this disease.

PMID- 10072488
TI  - Engagement of B cell receptor regulates the invariant chain-dependent MHC class
      II presentation pathway.
AB  - The intracellular sites in which Ags delivered by the B cell receptor (BCR) are
      degraded and loaded onto class II molecules remain poorly defined. To address
      this issue, we generated wild-type and invariant chain (Ii)-deficient H-2k mice
      bearing BCR specific for hen egg lysozyme. Our results show that, 1) unlike Ags
      taken up from the fluid phase, Ii is required for presentation of hen egg
      lysozyme internalized through the BCR in a manner independent of the peptide
      analyzed; 2) BCR ligation induces intracellular accumulation of MHC class II
      molecules only in Ii-positive B cells; and 3) these class II molecules reach
      intracellular compartments where BCR targets exogenous Ag. No differences in
      expression of adhesion and costimulatory molecules or in the presentation of
      soluble peptides were detectable between Ii-positive and -negative B cells.
      Therefore, the BCR delivers its ligand to compartments containing MHC class II-Ii
      complexes and bypasses the Ii-independent presentation pathway. The linked roles
      of Ag internalization and B cell activation of the BCR leads to potent Ii
      dependent presentation in splenic B cells.

PMID- 10072489
TI  - Tolerance to antigen-presenting cell-depleted islet allografts is CD4 T cell
      dependent.
AB  - Pretreatment of pancreatic islets in 95% oxygen culture depletes graft-associated
      APCs and leads to indefinite allograft acceptance in immunocompetent recipients.
      As such, the APC-depleted allograft represents a model of peripheral alloantigen
      presentation in the absence of donor-derived costimulation. Over time, a state of
      donor-specific tolerance develops in which recipients are resistant to donor APC
      induced graft rejection. Thus, persistence of the graft is sufficient to induce
      tolerance independent of other immune interventions. Donor-specific tolerance
      could be adoptively transferred to immune-deficient SCID recipient mice
      transplanted with fresh immunogenic islet allografts, indicating that the
      original recipient was not simply "ignorant" of donor antigens. Interestingly,
      despite the fact that the original islet allograft presented only MHC class I
      alloantigens, CD8+ T cells obtained from tolerant animals readily collaborated
      with naive CD4+ T cells to reject donor-type islet grafts. Conversely, tolerant
      CD4+ T cells failed to collaborate effectively with naive CD8+ T cells for the
      rejection of donor-type grafts. In conclusion, the MHC class I+, II- islet
      allograft paradoxically leads to a change in the donor-reactive CD4 T cell subset
      and not in the CD8 subset. We hypothesize that the tolerant state is not due to
      direct class I alloantigen presentation to CD8 T cells but, rather, occurs via
      the indirect pathway of donor Ag presentation to CD4 T cells in the context of
      host MHC class II molecules.

PMID- 10072490
TI  - Islet-specific Th1, but not Th2, cells secrete multiple chemokines and promote
      rapid induction of autoimmune diabetes.
AB  - Migration of CD4 cells into the pancreas represents a hallmark event in the
      development of insulin-dependent diabetes mellitus. Th1, but not Th2, cells are
      associated with pathogenesis leading to destruction of islet beta-cells and
      disease onset. Lymphocyte extravasation from blood into tissue is regulated by
      multiple adhesion receptor/counter-receptor pairs and chemokines. To identify
      events that regulate entry of CD4 cells into the pancreas, we transferred Th1 or
      Th2 cells induced in vitro from islet-specific TCR transgenic CD4 cells into
      immunodeficient (NOD.scid) recipients. Although both subsets infiltrated the
      pancreas and elicited multiple adhesion receptors (peripheral lymph node
      addressin, mucosal addressin cell adhesion molecule-1, LFA-1, ICAM-1, and VCAM-1)
      on vascular endothelium, entry/accumulation of Th1 cells was more rapid than that
      of Th2 cells, and only Th1 cells induced diabetes. In vitro, Th1 cells were also
      distinguished from Th2 cells by the capacity to synthesize several chemokines
      that included lymphotactin, monocyte chemoattractant protein-1 (MCP-1), and
      macrophage inflammatory protein-1alpha, whereas both subsets produced macrophage
      inflammatory protein-1beta. Some of these chemokines as well as RANTES, MCP-3,
      MCP-5, and cytokine-response gene-2 (CRG-2)/IFN-inducible protein-10 (IP-10) were
      associated with Th1, but not Th2, pancreatic infiltrates. The data demonstrate
      polarization of chemokine expression by Th1 vs Th2 cells, which, within the
      microenvironment of the pancreas, accounts for distinctive inflammatory
      infiltrates that determine whether insulin-producing beta-cells are protected or
      destroyed.

PMID- 10072491
TI  - Targeted deletion of the IgA constant region in mice leads to IgA deficiency with
      alterations in expression of other Ig isotypes.
AB  - A murine model of IgA deficiency has been established by targeted deletion of the
      IgA switch and constant regions in embryonic stem cells. B cells from IgA
      deficient mice were incapable of producing IgA in vitro in response to TGF-beta.
      IgA-deficient mice expressed higher levels of IgM and IgG in serum and
      gastrointestinal secretions and decreased levels of IgE in serum and pulmonary
      secretions. Expression of IgG subclasses was complex, with the most consistent
      finding being an increase in IgG2b and a decrease in IgG3 in serum and
      secretions. No detectable IgA Abs were observed following mucosal immunization
      against influenza; however, compared with those in wild-type mice, increased
      levels of IgM Abs were seen in both serum and secretions. Development of lymphoid
      tissues as well as T and B lymphocyte function appeared normal otherwise. Peyer's
      patches in IgA-deficient mice were well developed with prominent germinal centers
      despite the absence of IgA in these germinal centers or intestinal lamina
      propria. Lymphocytes from IgA-deficient mice responded to T and B cell mitogens
      comparable to those of wild-type mice, while T cells from IgA-deficient mice
      produced comparable levels of IFN-gamma and IL-4 mRNA and protein. In conclusion,
      mice with targeted deletion of the IgA switch and constant regions are completely
      deficient in IgA and exhibit altered expression of other Ig isotypes, notably
      IgM, IgG2b, IgG3, and IgE, but otherwise have normal lymphocyte development,
      proliferative responses, and cytokine production.

PMID- 10072492
TI  - Mucosal immunity to influenza without IgA: an IgA knockout mouse model.
AB  - IgA knockout mice (IgA-/-) were generated by gene targeting and were used to
      determine the role of IgA in protection against mucosal infection by influenza
      and the value of immunization for preferential induction of secretory IgA.
      Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates
      with sublethal and lethal doses of influenza virus resulted in similar levels of
      pulmonary virus infection and mortality. Intranasal and i.p. immunization with
      influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal
      and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-)
      mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited
      similar levels of pulmonary and nasal virus replication and mortality following a
      lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM,
      and polymeric IgA Abs were equally effective in preventing influenza virus
      infection in IgA-/- mice. These results indicate that IgA is not required for
      prevention of influenza virus infection and disease. Indeed, while mucosal
      immunization for selective induction of IgA against influenza may constitute a
      useful approach for control of influenza and other respiratory viral infections,
      strategies that stimulate other Igs in addition may be more desirable.

PMID- 10072493
TI  - B cell response after MMTV infection: extrafollicular plasmablasts represent the
      main infected population and can transmit viral infection.
AB  - The immune response to mouse mammary tumor virus (MMTV) relies on the
      presentation of an MMTV-encoded superantigen by infected B cells to superantigen
      specific T cells. The initial extrafollicular B cell differentiation involved the
      generation of B cells expressing low levels of B220. These B220low B cells
      corresponded to plasmablasts that expressed high levels of CD43 and syndecan-1
      and were CD62 ligand- and IgD-. Viral DNA was detected nearly exclusively in
      these B220low B cells by PCR, and retroviral type-A particles were observed in
      their cytoplasm by electron microscopy. An MMTV transmission to the offspring was
      also achieved after transfer of B220low CD62 ligand- CD43+ plasmablasts into
      noninfected females. These data suggest that B220low plasmablasts, representing
      the bulk of infected B cells, are capable of sustaining viral replication and may
      be involved in the transmission of MMTV.

PMID- 10072494
TI  - Cellular and molecular characterization of the scurfy mouse mutant.
AB  - Mice hemizygous (Xsf/Y) for the X-linked mutation scurfy (sf) develop a severe
      and rapidly fatal lymphoproliferative disease mediated by CD4+CD8- T lymphocytes.
      We have undertaken phenotypic and functional studies to more accurately identify
      the immunologic pathway(s) affected by this important mutation. Flow cytometric
      analyses of lymphoid cell populations reveal that scurfy syndrome is
      characterized by changes in several phenotypic parameters, including an increase
      in Mac-1+ cells and a decrease in B220+ cells, changes that may result from the
      production of extremely high levels of the cytokine granulocyte-macrophage CSF by
      scurfy T cells. Scurfy T cells also exhibit strong up-regulation of cell surface
      Ags indicative of in vivo activation, including CD69, CD25, CD80, and CD86. Both
      scurfy and normal T cells are responsive to two distinct signals provided by the
      TCR and by ligation of CD28; scurfy cells, however, are hyperresponsive to TCR
      ligation and exhibit a decreased requirement for costimulation through CD28
      relative to normal controls. This hypersensitivity may result, in part, from
      increased costimulation through B7-1 and B7-2, whose expression is up-regulated
      on scurfy T cells. Although the specific defect leading to this hyperactivation
      has not been identified, we also demonstrate that scurfy T cells are less
      sensitive than normal controls to inhibitors of tyrosine kinases such as
      genistein and herbimycin A, and the immunosuppressant cyclosporin A. One
      interpretation of our data would suggest that the scurfy mutation results in a
      defect, which interferes with the normal down-regulation of T cell activation.

PMID- 10072495
TI  - The EBV transforming protein, latent membrane protein 1, mimics and cooperates
      with CD40 signaling in B lymphocytes.
AB  - Latent membrane protein 1 (LMP1) is required for EBV-induced immortalization of
      human B cells, and expression of the protein in the absence of other viral
      proteins leads to an activated phenotype in B cells. It has been well documented
      that LMP1 causes B cells to up-regulate adhesion molecules, such as LFA-1 and
      ICAM-1, and coactivation molecules, such as B7-1 and CD23, as well as to activate
      NF-kappaB. Ligation of the endogenous B cell CD40 molecule also induces these and
      other activated phenotypic changes. Here, we report that expression of LMP1 also
      activates B cells to secrete Ig and IL-6 and rescues them from B cell receptor
      mediated growth arrest analogous to CD40 signaling. Furthermore, an HLA-A2LMP1
      chimeric construct demonstrates that the oligomerization of the carboxyl-terminal
      200 amino acids of LMP1 is sufficient for B cell signaling. Finally, we
      demonstrate that LMP1 and CD40 signaling pathways interact cooperatively in
      inducing B cell effector functions.

PMID- 10072496
TI  - TRANCE, a TNF family member, is differentially expressed on T cell subsets and
      induces cytokine production in dendritic cells.
AB  - TNF-related activation-induced cytokine (TRANCE) is a member of the TNF family
      recently identified in activated T cells. We report here that TRANCE mRNA is
      constitutively expressed in memory, but not naive, T cells and in single-positive
      thymocytes. Upon TCR/CD3 stimulation, TRANCE mRNA and surface protein expression
      are rapidly up-regulated in CD4+ and CD8+ T cells, which can be further enhanced
      on CD4+ T cells by CD28-mediated costimulation. However, TRANCE induction is
      significantly suppressed when cells are stimulated in the presence of IL-4, but
      is not modified in the presence of IFN-alpha, IFN-gamma, TGF-beta, TNF-alpha, or
      IL-2. High levels of TRANCE receptor expression are found on mature dendritic
      cells (DCs). In this study we show that activated T and B cells also express
      TRANCE receptor, but only at low levels. TRANCE, however, does not exert any
      significant effect on the proliferation, activation, or survival of those cells.
      In DCs, TRANCE induces the expression of proinflammatory cytokines (IL-6, IL-1)
      and T cell growth and differentiation factors (IL-12, IL-15) in addition to
      enhancing DC survival. Moreover, TRANCE cooperates with CD40 ligand or TNF-alpha
      to further increase the viability of DCs, suggesting that several TNF-related
      molecules on activated T cells may cooperatively regulate the function and
      survival of DCs to enhance T cell-mediated immune responses.

PMID- 10072497
TI  - N-acetyl-L-cysteine inhibits primary human T cell responses at the dendritic cell
      level: association with NF-kappaB inhibition.
AB  - N-acetyl-L-cysteine (NAC) is an antioxidant molecule endowed with
      immunomodulatory properties. To investigate the effect of NAC on the induction
      phase of T cell responses, we analyzed its action on human dendritic cells (DC)
      derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CSF. We
      first found that NAC inhibited the constitutive as well as the LPS-induced
      activity of the transcription factor NF-kappaB. In parallel, NAC was shown to
      down-regulate the production of cytokines by DC as well as their surface
      expression of HLA-DR, CD86 (B7-2), and CD40 molecules both at the basal state and
      upon LPS activation. NAC also inhibited DC responses induced by CD40 engagement.
      The inhibitory effects of NAC were not due to nonspecific toxicity as neither the
      viability of DC nor their mannose receptor-mediated endocytosis were modified by
      NAC. Finally, we found that the addition of NAC to MLR between naive T cells and
      allogeneic DC resulted in a profound inhibition of alloreactive responses, which
      could be attributed to a defect of DC as APC-independent T cell responses were
      not inhibited by NAC. Altogether, our results suggest that NAC might impair the
      generation of primary immune responses in humans through its inhibitory action on
      DC.

PMID- 10072498
TI  - Characterization of TCR gene rearrangements during adult murine T cell
      development.
AB  - Development of the alphabeta and gammadelta T cell lineages is dependent upon the
      rearrangement and expression of the TCRalpha and beta or gamma and delta genes,
      respectively. Although the timing and sequence of rearrangements of the TCRalpha
      and TCRbeta loci in adult murine thymic precursors has been characterized, no
      similar information is available for the TCRgamma and TCRdelta loci. In this
      report, we show that approximately half of the total TCRdelta alleles initiate
      rearrangements at the CD44highCD25+ stage, whereas the TCRbeta locus is mainly in
      germline configuration. In the subsequent CD44lowCD25+ stage, most TCRdelta
      alleles are fully recombined, whereas TCRbeta rearrangements are only complete on
      10-30% of alleles. These results indicate that rearrangement at the TCRdelta
      locus can precede that of TCRbeta locus recombination by one developmental stage.
      In addition, we find a bias toward productive rearrangements of both TCRdelta and
      TCRgamma genes among CD44highCD25+ thymocytes, suggesting that functional
      gammadelta TCR complexes can be formed before the rearrangement of TCRbeta. These
      data support a model of lineage commitment in which sequential TCR gene
      rearrangements may influence alphabeta/gammadelta lineage decisions. Further,
      because TCR gene rearrangements are generally limited to T lineage cells, these
      analyses provide molecular evidence that irreversible commitment to the T lineage
      can occur as early as the CD44highCD25+ stage of development.

PMID- 10072499
TI  - Genome-wide linkage analysis of chronic relapsing experimental autoimmune
      encephalomyelitis in the rat identifies a major susceptibility locus on
      chromosome 9.
AB  - The immunization of inbred Dark Agouti (DA) rats with an emulsion containing
      homogenized spinal cord and CFA induces chronic relapsing experimental autoimmune
      encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis.
      We report here the first genome-wide search for quantitative trait loci
      regulating EAE in the rat using this model. We identified one quantitative trait
      locus on chromosome 9, Eae4, in a [DA(RT1av1) x BN(RT1n)]F2 intercross showing
      linkage to disease susceptibility and expression of mRNA for the proinflammatory
      cytokine IFN-gamma in the spinal cord. Eae4 had a larger influence on disease
      incidence among rats that were homozygous for the RT1av1 MHC haplotype (RT1av1
      rats) compared with RT1n/av1 rats, suggesting an interaction between Eae4 and the
      MHC. Homozygosity for the DA allele at markers in Eae4 and in the MHC was
      sufficient for EAE. Thus, Eae4 is a major genetic factor determining
      susceptibility to EAE in this cross of DA rats. In addition, there was support
      for linkage to phenotypes of EAE on chromosomes 1, 2, 5, 7, 8, 12, and 15. The
      chromosome 12 region has been shown previously to predispose DA rats to
      arthritis, and the chromosome 2 region is syntenic to Eae3 in mice. We conclude
      that Eae4 and probably the other identified genome regions harbor genes
      regulating susceptibility to neuroinflammatory disease. The identification and
      functional characterization of these genes may disclose critical events in the
      pathogenesis of multiple sclerosis; understanding these events could be essential
      for the development of new therapies against the disease.

PMID- 10072500
TI  - Surface expression and functional competence of CD3-independent TCR zeta-chains
      in immature thymocytes.
AB  - In recombinase-deficient (RAG-2-/-) mice, double-negative thymocytes can be
      stimulated to proliferate and differentiate by anti-CD3 Abs. CD3 molecules are
      expressed on the surface of these cells in association with calnexin. In this
      study, we show that zeta-chains can be recovered as phosphorylated proteins in
      association with phosphorylated ZAP-70 from anti-CD3-stimulated RAG-2-/-
      thymocytes, even though they are not demonstrably associated with the
      CD3/calnexin complex. The lack of a physical association of zeta dimers with the
      CD3 complex in RAG-2-/- thymocytes and also in a pre-TCR-expressing cell line, as
      well as the efficient association of zeta dimers with ZAP-70 in the RAG-2-/-
      thymocytes, suggest that these zeta-chain dimers could contribute to pre-TCR
      signaling. This idea is supported by the finding that in RAG-2-/- zeta-deficient
      thymocytes, ZAP-70 and p120cbl were only weakly phosphorylated.

PMID- 10072501
TI  - Functional analysis of TRAIL receptors using monoclonal antibodies.
AB  - mAbs were generated against the extracellular domain of the four known TNF
      related apoptosis-inducing ligand (TRAIL) receptors and tested on a panel of
      human melanoma cell lines. The specificity of the mAb permitted a precise
      evaluation of the TRAIL receptors that induce apoptosis (TRAIL-R1 and -R2)
      compared with the TRAIL receptors that potentially regulate TRAIL-mediated
      apoptosis (TRAIL-R3 and -R4). Immobilized anti-TRAIL-R1 or -R2 mAbs were
      cytotoxic to TRAIL-sensitive tumor cells, whereas tumor cells resistant to
      recombinant TRAIL were also resistant to these mAbs and only became sensitive
      when cultured with actinomycin D. The anti-TRAIL-R1 and -R2 mAb-induced death was
      characterized by the activation of intracellular caspases, which could be blocked
      by carbobenzyloxy-Val-Ala-Asp (OMe) fluoromethyl ketone (zVAD-fmk) and
      carbobenzyloxy-Ile-Glu(OMe)-Thr-Asp (OMe) fluoromethyl ketone (zIETD-fmk). When
      used in solution, one of the anti-TRAIL-R2 mAbs was capable of blocking leucine
      zipper-human TRAIL binding to TRAIL-R2-expressing cells and prevented TRAIL
      induced death of these cells, whereas two of the anti-TRAIL-R1 mAbs could inhibit
      leucine zipper-human TRAIL binding to TRAIL-R1:Fc. Furthermore, use of the
      blocking anti-TRAIL-R2 mAb allowed us to demonstrate that the signals transduced
      through either TRAIL-R1 or TRAIL-R2 were necessary and sufficient to mediate cell
      death. In contrast, the expression of TRAIL-R3 or TRAIL-R4 did not appear to be a
      significant factor in determining the resistance or sensitivity of these tumor
      target cells to the effects of TRAIL.

PMID- 10072502
TI  - IL-15 induces the expression of chemokines and their receptors in T lymphocytes.
AB  - IL-15 is a T cell growth factor that shares many biological activities with IL-2
      and uses the same beta/gamma polypeptides of the IL-2R complex for signal
      transduction. Accumulating evidence implicates an important role for this
      cytokine in the inflammatory response of the host. Consistent with such a role,
      IL-15 has been shown to be a chemoattractant for T lymphocytes, NK cells, and
      neutrophils. Extending these observations, we now show that IL-15 is a potent
      inducer of CC-, CXC-, and C-type chemokines in T lymphocytes. In addition, we
      demonstrate that IL-15 induces CC chemokine receptors, but not CXC chemokine
      receptors, in a dose-dependent manner. Thus, our findings suggest that the
      proinflammatory effects of IL-15 at least in part may be due to the induction of
      chemokines and their receptors in T cells. Furthermore, we demonstrate that IL-15
      promotes entry and replication of macrophage-tropic HIV in T lymphocytes and
      suggest a plausible mechanism by which IL-15, a cytokine that is elevated in HIV
      infected individuals, may promote the transition of HIV displaying the M-tropic
      phenotype primarily associated with the initial transmission into the T cell
      tropic phenotype that predominates as the disease progresses.

PMID- 10072503
TI  - IL-4 and IL-10 are both required for the induction of oral tolerance.
AB  - Protection from the development of experimental autoimmune uveitis (EAU) can be
      induced by feeding mice interphotoreceptor retinoid binding protein before
      uveitogenic challenge with the same protein. Two different regimens are equally
      effective in inducing protective tolerance, although they seem to do so through
      different mechanisms: one involving regulatory cytokines (IL-4, IL-10, and TGF
      beta), and the other with minimal involvement of cytokines. Here we studied the
      importance of IL-4 and IL-10 for the development of oral tolerance using mice
      genetically engineered to lack either one or both of these cytokines. In these
      animals we were able to protect against EAU only through the regimen inducing
      cytokine-independent tolerance. When these animals were fed a regimen that in the
      wild-type animal is thought to predominantly induce regulatory cells and is
      associated with cytokine secretion, they were not protected from EAU.
      Interestingly, both regimens were associated with reduced IL-2 production and
      proliferation in response to interphotoreceptor retinoid binding protein. These
      findings indicate that both IL-4 and IL-10 are required for induction of
      protective oral tolerance dependent on regulatory cytokines, and that one
      cytokine cannot substitute for the other in this process. These data also
      underscore the fact that oral tolerance, manifested as suppression of
      proliferation and IL-2 production, is not synonymous with protection from
      disease.

PMID- 10072504
TI  - Analysis of MHC class II genes in the susceptibility to lupus in New Zealand
      mice.
AB  - Hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously
      develop a disease similar to human systemic lupus erythematosus. MHC and non-MHC
      genes contribute to disease susceptibility in this murine model. Multiple studies
      have shown that the NZW H2z locus is strongly associated with the development of
      lupus-like disease in these mice. The susceptibility gene(s) within H2z is not
      known, but different lines of evidence have pointed to class II MHC genes, either
      H2-E or H2-A (Ez or Az in NZW). Recent studies from our laboratory showed that Ez
      does not supplant H2z in the contribution to lupus-like disease. In the present
      work we generated C57BL/10 (B10) mice transgenic for Aaz and Abz genes
      (designated B10.Az mice) and used a (B10.Az x NZB)F1 x NZB backcross to assess
      the contributions of Az genes to disease. A subset of backcross mice produced
      high levels of IgG autoantibodies and developed severe nephritis. However, no
      autoimmune phenotype was linked to the Az transgenes. Surprisingly, in the same
      backcross mice, inheritance of H2b from the nonautoimmune B10 strain was strongly
      linked with both autoantibody production and nephritis. Taken together with our
      previous Ez studies, the present work calls into question the importance of class
      II MHC genes for lupus susceptibility in this model and provides new insight into
      the role of MHC in lupus-like autoimmunity.

PMID- 10072505
TI  - Potent inhibition of CD4/TCR-mediated T cell apoptosis by a CD4-binding
      glycoprotein secreted from breast tumor and seminal vesicle cells.
AB  - We previously isolated a CD4 ligand glycoprotein, gp17, from human seminal
      plasma; this glycoprotein is identical with gross cystic disease fluid protein-15
      (GCDFP-15), a factor specifically secreted from primary and secondary breast
      tumors. The function of gp17/GCDFP-15 in physiological as well as in pathological
      conditions has remained elusive thus far. As a follow up to our previous findings
      that gp17 binds to CD4 with high affinity and interferes with both HIV-1 gp120
      binding to CD4 and syncytium formation, we investigated whether gp17 could affect
      the T lymphocyte apoptosis induced by a separate ligation of CD4 and TCR. We show
      here that gp17/GCDFP-15 is in fact a strong and specific inhibitor of the T
      lymphocyte programmed cell death induced by CD4 cross-linking and subsequent TCR
      activation. The antiapoptotic effect observed in the presence of gp17 correlates
      with a moderate up-regulation of Bcl-2 expression in treated cells. The presence
      of gp17 also prevents the down-modulation of Bcl-2 expression in Bcl-2bright CD4+
      T cells that is caused by the triggering of apoptosis. Our results suggest that
      gp17 may represent a new immunomodulatory CD4 binding factor playing a role in
      host defense against infections and tumors.

PMID- 10072506
TI  - Involvement of TNF-related apoptosis-inducing ligand in human CD4+ T cell
      mediated cytotoxicity.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) has been identified as a member of
      the TNF family that induces apoptosis in a variety of tumor cells, but its
      physiological functions are largely unknown. In the present study, we examined
      the expression and function of TRAIL in human CD4+ T cell clones by utilizing
      newly established anti-human TRAIL mAbs. Human CD4+ T cell clones, HK12 and 4HM1,
      exhibited perforin-independent and Fas ligand (FasL)-independent cytotoxicity
      against certain target cells, including T lymphoma (Jurkat) and keratinocyte
      (HaCaT) cell lines, which are susceptible to TRAIL-mediated cytotoxicity. In
      contrast to FasL, the expression of which was inducible upon anti-CD3
      stimulation, TRAIL was constitutively expressed on HK12 and 4HM1 cells, and no
      further increase was observed after anti-CD3 stimulation. Spontaneous cytotoxic
      activities of resting HK12 and 4HM1 cells against Jurkat and HaCaT cells were
      blocked by anti-TRAIL mAb but not by anti-FasL mAb, and bystander cytotoxic
      activities of anti-CD3-stimulated HK12 and 4HM1 cells were abolished by the
      combination of anti-TRAIL and anti-FasL mAbs. These results indicate a
      differential regulation of TRAIL and FasL expression on human CD4+ T cell clones
      and that TRAIL constitutes an additional pathway of T cell-mediated cytotoxicity.

PMID- 10072507
TI  - Pregnancy ameliorates induction and expression of experimental autoimmune
      uveitis.
AB  - Female patients suffering from autoimmune uveitis are reported to experience a
      temporary remission during pregnancy. Experimental autoimmune uveitis (EAU) is a
      model for human uveitis. Here we examine the effect of pregnancy on the
      development of EAU and its associated immunological responses. Susceptible
      C57BL/6 mice were immunized with interphotoreceptor retinoid-binding protein
      (IRBP). EAU scores and Ag-specific responses were evaluated 21 days later. Mice
      immunized during pregnancy developed significantly less EAU than nonpregnant
      controls. Their lymph node cells and splenocytes produced a distinct pattern of
      cytokines in response to IRBP: reduced IFN-gamma and IL-12 p40, but unchanged
      levels of TNF-alpha, IL-4, IL-5, and IL-10. Anti-IRBP Ab isotypes revealed an up
      regulation of IgG1, indicating a possible Th2 bias at the humoral level. Ag
      specific proliferation and delayed hypersensitivity, as well as mitogen-induced
      IFN-gamma production, remained undiminished, arguing against an overall immune
      deficit. Interestingly, pregnant mice that received an infusion of IRBP-primed
      lymphoid cells from nonpregnant donors also developed reduced EAU, suggesting
      that pregnancy suppresses not only the generation, but also the function of
      mature uveitogenic effector T cells. Pregnant mice at the time of immunization
      exhibited elevated levels of TGF-beta, but not of IL-10, in the serum. We suggest
      that protection from EAU during pregnancy is due primarily to a selective
      reduction of Ag-specific Th1 responses with only marginal enhancement of Th2
      function, and that these effects may in part be secondary to elevated systemic
      levels of TGF-beta.

PMID- 10072508
TI  - Antigen receptor-induced signal transduction imbalances associated with the
      negative selection of immature B cells.
AB  - Signals transduced through the B cell Ag receptor (BCR) drive B cell development.
      However, BCR-induced responses are developmentally regulated; immature B cells
      are tolerized following antigenic exposure while mature B cells are triggered to
      proliferate and differentiate. This differential responsiveness allows for the
      negative selection of self-reactive immature B cells while simultaneously
      allowing for clonal expansion of mature B cells in response to foreign Ags.
      Intrinsic differences in BCR-induced signal transduction at various stages of
      development may account for this functional dichotomy. We had previously
      demonstrated that the BCR-induced proliferation of mature B cells is accompanied
      by an increase in intracellular calcium levels and polyphosphoinositide bis
      phosphate (PIP2) hydrolysis. In contrast, immature B cells that undergo BCR
      induced apoptosis increase intracellular calcium in the relative absence of PIP2
      hydrolysis. Since PIP2 hydrolysis leads to the generation of diacylglycerol, a
      cofactor for protein kinase C (PKC) activation, these data suggested that an
      "imbalance" in BCR-induced signal transduction resulting from a relative
      inability to activate PKC may play a role in the susceptibility of immature B
      cells to BCR-induced apoptosis. In support of this hypothesis, we demonstrate
      that PKC activation can rescue immature B cells from BCR-induced apoptosis.
      Furthermore, the susceptibility of immature B cells to BCR-induced apoptosis is
      recapitulated in mature B cells that are either PKC depleted or are stimulated in
      the presence of PKC inhibitors, suggesting that an uncoupling of PKC activation
      from BCR-induced signaling is responsible for the apoptotic response of immature
      B cells.

PMID- 10072509
TI  - Enhanced cytotoxic T cell activity in IL-4-deficient mice.
AB  - CD8+ effectors are critical components of type 1 responses against viral
      infections as well as for antiviral vaccines. IL-4 plays a clear role as an
      inhibitor of CD4+ Th1 cells; however, its role in CD8+ T cell regulation appears
      to be more complex. Thus, IL-4 may augment CD8+ T cell growth, but also limit
      effector function. Moreover, abundant IL-4 is inhibitory for viral clearance, but
      the lack of IL-4 appears not to affect CTL-mediated immunity. This report
      investigates these disparate roles of IL-4 in CD8+ T lymphocyte regulation by
      comparing T cell responses specific for a single HIV-IIIIB gp120-derived epitope
      in BALB/c mice deficient in IL-4 to those in wild-type controls. CTL activation
      was monitored during the acute and memory phases following immunization with
      recombinant vaccinia virus. Similar frequencies of gp120-specific CTL precursors
      in splenocytes from both groups indicated that IL-4 plays no significant role in
      either CTL priming or the establishment of memory. However, cytolytic activity in
      cultures derived from IL-4-deficient mice developed earlier and was strikingly
      enhanced following in vitro restimulation, an effect exhibited by both primary
      and memory T cells. Secretion of IL-2 and IFN-gamma by CD8+ T cells from IL-4
      deficient mice was also elevated, reflecting their enhanced activation. Thus, IL
      4 appears to limit the activation, expansion, and differentiation of CD8+ T cells
      with high cytolytic potential.

PMID- 10072510
TI  - Soluble class I MHC with beta2-microglobulin covalently linked peptides: specific
      binding to a T cell hybridoma.
AB  - Soluble forms of the mouse MHC class I molecule, Dd, were produced in which the
      peptide binding groove was uniformly occupied by peptides attached via a covalent
      flexible peptide linker to the N terminus of the associated beta2-microglobulin.
      The MHC heavy chain and beta2-microglobulin were firmly associated, and the
      molecules displayed an Ab epitope requiring proper occupancy of the peptide
      binding groove. Soluble Dd containing a covalent version of a well-characterized
      Dd-binding peptide from HIV stimulated a T cell hybridoma specific for this
      combination. Furthermore, a tetravalent version of this molecule bound
      specifically with apparent high avidity to this hybridoma.

PMID- 10072511
TI  - Regulators of G protein signaling exhibit distinct patterns of gene expression
      and target G protein specificity in human lymphocytes.
AB  - The newly recognized regulators of G protein signaling (RGS) attenuate
      heterotrimeric G protein signaling pathways. We have cloned an IL-2-induced gene
      from human T cells, cytokine-responsive gene 1, which encodes a member of the RGS
      family, RGS16. The RGS16 protein binds Gialpha and Gqalpha proteins present in T
      cells, and inhibits Gi- and Gq-mediated signaling pathways. By comparison, the
      mitogen-induced RGS2 inhibits Gq but not Gi signaling. Moreover, the two RGS
      genes exhibit marked differences in expression patterns. The IL-2-induced
      expression of the RGS16 gene in T cells is suppressed by elevated cAMP, whereas
      the RGS2 gene shows a reciprocal pattern of regulation by these stimuli. Because
      the mitogen and cytokine receptors that trigger expression of RGS2 and RGS16 in T
      cells do not activate heterotrimeric G proteins, these RGS proteins and the G
      proteins that they regulate may play a heretofore unrecognized role in T cell
      functional responses to Ag and cytokine activation.

PMID- 10072512
TI  - Oligoclonality of rat intestinal intraepithelial T lymphocytes: overlapping TCR
      beta-chain repertoires in the CD4 single-positive and CD4/CD8 double-positive
      subsets.
AB  - Previous studies in humans and mice have shown that gut intraepithelial
      lymphocytes (IELs) express oligoclonal TCR beta-chain repertoires. These studies
      have either employed unseparated IEL preparations or focused on the CD8+ subsets.
      Here, we have analyzed the TCR beta-chain repertoire of small intestinal IELs in
      PVG rats, in sorted CD4+ as well as CD8+ subpopulations, and important
      differences were noted. CD8alphaalpha and CD8alphabeta single-positive (SP) IELs
      used most Vbeta genes, but relative Vbeta usage as determined by quantitative PCR
      analysis differed markedly between the two subsets and among individual rats. By
      contrast, CD4+ IELs showed consistent skewing toward Vbeta17 and Vbeta19; these
      two genes accounted collectively for more than half the Vbeta repertoire in the
      CD4/CD8 double-positive (DP) subset and were likewise predominant in CD4 SP IELs.
      Complementarity-determining region 3 length displays and TCR sequencing
      demonstrated oligoclonal expansions in both the CD4+ and CD8+ IEL subpopulations.
      These studies also revealed that the CD4 SP and CD4/CD8 DP IEL subsets expressed
      overlapping beta-chain repertoires. In conclusion, our results show that rat TCR
      alphabeta+ IELs of both the CD8+ and CD4+ subpopulations are oligoclonal. The
      limited Vbeta usage and overlapping TCR repertoire expressed by CD4 SP and
      CD4/CD8 DP cells suggest that these two IEL populations recognize restricted
      intestinal ligands and are developmentally and functionally related.

PMID- 10072513
TI  - CD38 signaling in B lymphocytes is controlled by its ectodomain but occurs
      independently of enzymatically generated ADP-ribose or cyclic ADP-ribose.
AB  - CD38 is a type II transmembrane glycoprotein that is expressed by many cell types
      including lymphocytes. Signaling through CD38 on B lymphocytes can mediate B cell
      activation, proliferation, and cytokine secretion. Additionally, coligation of
      CD38 and the B cell Ag receptor can greatly augment B cell Ag receptor responses.
      Interestingly, the extracellular domain of CD38 catalyzes the conversion of NAD+
      into nicotinamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR). cADPR can induce
      intracellular calcium release in an inositol trisphosphate-independent manner and
      has been hypothesized to regulate CD38-mediated signaling. We demonstrate that
      replacement of the cytoplasmic tail and the transmembrane domains of CD38 did not
      impair CD38 signaling, coreceptor activity, or enzyme activity. In contrast,
      independent point mutations in the extracellular domain of CD38 dramatically
      impaired signal transduction. However, no correlation could be found between CD38
      mediated signaling and the capacity of CD38 to catalyze an enzyme reaction and
      produce cADPR, ADPR, and/or nicotinamide. Instead, we propose that CD38 signaling
      and coreceptor activity in vitro are regulated by conformational changes induced
      in the extracellular domain upon ligand/substrate binding, rather than on actual
      turnover or generation of products.

PMID- 10072514
TI  - IL-4 preferentially activates a novel STAT6 isoform in mast cells.
AB  - IL-4 is a pleiotropic cytokine that signals through STAT6 to direct the
      transactivation of multiple gene targets. In this study, we demonstrate that mast
      cells express a distinct STAT6 isoform. This "mast cell STAT" is a product of the
      STAT6 gene, but is only 65 kDa in size and appears to lack the defined C-terminal
      transactivation domain. Despite the presence of the conventional 94-kDa STAT6
      molecule, it is the smaller isoform that associates with a consensus STAT6
      binding site in extracts from IL-4-treated mast cells. This is the first evidence
      that STAT6 isoforms can be preferentially activated and bind to DNA in a cell
      specific manner. These results imply that an additional level of specificity in
      the IL-4R signaling mechanism exists and may partially explain the diverse
      effects that IL-4 exerts on different cell types.

PMID- 10072515
TI  - Overlapping roles for L-selectin and P-selectin in antigen-induced immune
      responses in the microvasculature.
AB  - Although L-selectin mediates lymphocyte attachment to endothelial venules of
      peripheral lymph nodes, its role in leukocyte recruitment into tissues following
      Ag challenge is less well established. The objective of this study was to
      systematically examine the role of L-selectin in leukocyte rolling in the
      peripheral microvasculature during the first 24 h of an immune response. A type I
      hypersensitivity response was elicited in wild-type (C57BL/6) and L-selectin
      deficient mice by systemic (i.p.) sensitization and intrascrotal challenge with
      chicken egg OVA. The cremaster microcirculation was observed in untreated and
      sensitized mice 4, 8, and 24 h post-Ag challenge by intravital microscopy.
      Leukocyte recruitment in L-selectin-deficient mice and wild-type mice treated
      with an L-selectin function-blocking mAb was examined at each time point. Ag
      challenge induced a significant increase in leukocyte rolling (60
      cells/min/venule to approximately 300 cells/min/venule) in wild-type mice at 4-24
      h. This response was reduced by approximately 60-70% in L-selectin-deficient mice
      and in wild-type mice treated with an L-selectin-blocking mAb. P-selectin
      blockade by Ab completely inhibited leukocyte rolling at 4-24 h in wild-type
      animals and also blocked the residual rolling seen in L-selectin-deficient mice.
      Blocking E-selectin function had no effect on leukocyte rolling flux at any time
      point in wild-type or L-selectin-deficient mice. Despite reduced rolling,
      leukocyte adhesion and emigration were not measurably reduced in the L-selectin
      deficient mice in this vascular bed. In conclusion, leukocyte rolling is L
      selectin-dependent post-Ag challenge with L-selectin and P-selectin sharing
      overlapping functions.

PMID- 10072516
TI  - Expression of dominant-negative src-homology domain 2-containing protein tyrosine
      phosphatase-1 results in increased Syk tyrosine kinase activity and B cell
      activation.
AB  - The Src-homology domain 2 (SH2)-containing cytoplasmic tyrosine phosphatase, SHP
      1 (SH2-containing protein tyrosine phosphatase-1), interacts with several B cell
      surface and intracellular signal transduction molecules through its SH2 domains.
      Mice with the motheaten and viable motheaten mutations are deficient in SHP-1 and
      lack most mature B cells. To define the role of SHP-1 in mature B cells, we
      expressed phosphatase-inactive SHP-1 (C453S) in a mature B cell lymphoma line.
      SHP-1 (C453S) retains the ability to bind to both substrates and appropriate
      tyrosine-phosphorylated proteins and therefore can compete with the endogenous
      wild-type enzyme. We found that B cells expressing SHP-1 (C453S) demonstrated
      enhanced and prolonged tyrosine phosphorylation of proteins with molecular masses
      of 110, 70, and 55-60 kDa after stimulation with anti-mouse IgG. The tyrosine
      kinase Syk was hyperphosphorylated and hyperactive in B cells expressing SHP-1
      (C453S). SHP-1 and Syk were coimmunoprecipitated from wild-type K46 cells, K46
      SHP-1 (C453S) cells, and splenic B cells, and SHP-1 dephosphorylated Syk. Cells
      expressing SHP-1 (C453S) showed increased Ca2+ mobilization, extracellular signal
      regulated kinase activation, and homotypic adhesion after B cell Ag receptor
      engagement. Thus, SHP-1 regulates multiple early and late events in B lymphocyte
      activation.

PMID- 10072517
TI  - Emergence of T cell progenitors without B cell or myeloid differentiation
      potential at the earliest stage of hematopoiesis in the murine fetal liver.
AB  - It has been unclear whether the progenitors colonizing the thymus are multipotent
      or T cell lineage restricted. We investigated the developmental potential of
      hematopoietic progenitors in various populations of liver and blood cells from
      day 12 fetuses using the recently established in vitro experimental system
      effective in determining the capability of individual progenitors to generate T,
      B, and myeloid cells. Multipotent progenitors (p-Multi) were exclusively found in
      the Sca-1 high-positive (Sca-1high) subpopulation of lineage marker (Lin)-c
      kit+CD45+ fetal liver cells. Restriction of developmental capacity begins at the
      Sca-1high stage, and a large majority of progenitors in the Sca-1low or Sca-1-
      population are restricted to generate T, B, or myeloid cells. Such a lineage
      commitment or restriction taking place in the fetal liver is independent of the
      thymus, because no difference in the proportion of different types of progenitors
      were seen between nu/nu and nu/+ fetuses. T cell lineage-restricted progenitors
      (p-T) were abundant in the blood of day 12 fetuses, whereas p-Multi were
      undetectable. It was further shown that the p-Multi generated a large number of B
      and myeloid cells in the thymic lobe. These results strongly suggest that it is p
      T but not p-Multi that migrate into the thymus.

PMID- 10072518
TI  - Regulation of B cell receptor-mediated MHC class II antigen processing by
      FcgammaRIIB1.
AB  - The processing and presentation of Ag by Ag-specific B cells is highly efficient
      due to the dual function of the B cell Ag receptor (BCR) in both signaling for
      enhanced processing and endocytosing bound Ag. The BCR for IgG (FcgammaRIIB1) is
      a potent negative coreceptor of the BCR that blocks Ag-induced B cell
      proliferation. Here we investigate the influence of the FcgammaRIIB1 on BCR
      mediated Ag processing and show that coligating the FcgammaRIIB1 and the BCR
      negatively regulates both BCR signaling for enhanced Ag processing and BCR
      mediated Ag internalization. Treatment of splenic B cells with F(ab')2 anti-Ig
      significantly enhances APC function compared with the effect of whole anti-Ig;
      however, whole anti-Ig treatment is effective when binding to the FcgammaRIIB1
      was blocked by a FcgammaRII-specific mAb. Processing and presentation of Ag
      covalently coupled to anti-Ig were significantly decreased compared with Ag
      coupled to F(ab')2anti-Ig; however, the processing of the two Ag-Ab conjugates
      was similar in cells that did not express FcgammaRIIB1 and in splenic B cells
      treated with a FcgammaRII-specific mAb to block Fc binding. Internalization of
      monovalent Ag by B cells was reduced in the presence of whole anti-Ig as compared
      with F(ab')2 anti-Ig, but the internalized Ag was correctly targeted to the class
      II peptide loading compartment. Taken together, these results indicate that the
      FcgammaRIIB1 is a negative regulator of the BCR-mediated Ag-processing function.

PMID- 10072519
TI  - Reduced generation but efficient TCR beta-chain selection of CD4+8+ double
      positive thymocytes in mice with compromised CD3 complex signaling.
AB  - Maturation to the CD4+8+ double-positive (DP) stage of thymocyte development is
      restricted to cells that have passed TCRbeta selection, an important checkpoint
      at which immature CD4-8- double-negative (DN) cells that express TCRbeta
      polypeptide chains are selected for further maturation. The generation of DP
      thymocytes following TCRbeta selection is dependent on cellular survival,
      differentiation, and proliferation, and the entire process appears to be mediated
      by the pre-TCR/CD3 complex. In this study, we investigate the signaling
      requirements for TCRbeta selection using mice single deficient and double
      deficient for CD3zeta/eta and/or p56lck. While the numbers of DP cells are
      strongly reduced in the single-deficient mice, a further drastic reduction in the
      generation of DP thymocytes is seen in the double-deficient mice. The poor
      generation of DP cells in the mutant mice is primarily due to an impaired ability
      of CD25+ DN thymocytes to proliferate following expression of a TCRbeta-chain.
      Nevertheless, the residual DP cells in all mutant mice are strictly selected for
      expression of TCRbeta polypeptide chains. DN thymocytes of mutant mice expressed
      TCRbeta and CD3epsilon at the cell surface and contained mRNA for pre-Talpha, but
      not for clonotypic TCRalpha-chains, together suggesting that TCRbeta selection is
      mediated by pre-TCR signaling in all cases. The data suggest differential
      requirements of pre-TCR signaling for cell survival on the one hand, and for the
      proliferative burst associated with TCRbeta selection on the other.

PMID- 10072520
TI  - Lymphocyte activation gene-3, a MHC class II ligand expressed on activated T
      cells, stimulates TNF-alpha and IL-12 production by monocytes and dendritic
      cells.
AB  - Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand structurally and
      genetically related to CD4. Although its expression is restricted to activated T
      cells and NK cells, the functions of LAG-3 remain to be elucidated. Here, we
      report on the expression and function of LAG-3 on proinflammatory bystander T
      cells that are activated in the absence of TCR engagement. LAG-3 is expressed at
      high levels on human T cells cocultured with autologous monocytes and IL-2 and
      synergizes with the low levels of CD40 ligand (CD40L) expressed on these cells to
      trigger TNF-alpha and IL-12 production by monocytes. Indeed, anti-LAG-3 mAb
      inhibits both IL-12 and IFN-gamma production in IL-2-stimulated cocultures of T
      cells and autologous monocytes. Soluble LAG-3Ig fusion protein markedly enhances
      IL-12 production by monocytes stimulated with infra-optimal concentrations of
      sCD40L, whereas it directly stimulates monocyte-derived dendritic cells (DC) for
      the production of TNF-alpha and IL-12, unravelling an enhanced responsiveness to
      MHC class II engagemenent in DC as compared with activated monocytes. Thus
      similar to CD40L, LAG-3 may be involved in the proinflammatory activity of
      cytokine-activated bystander T cells and most importantly it may directly
      activate DC.

PMID- 10072522
TI  - Dissecting NK cell development using a novel alymphoid mouse model: investigating
      the role of the c-abl proto-oncogene in murine NK cell differentiation.
AB  - NK lymphocytes participate in both innate and adaptive immunity by their prompt
      secretion of cytokines including IFN-gamma, which activates macrophages, and by
      their ability to lyse virally infected cells and tumor cells without prior
      sensitization. Although these characteristics of NK cells are well documented,
      little is known about the genetic program that orchestrates NK development or
      about the signaling pathways that trigger NK effector functions. By crossing NK
      deficient common gamma-chain (gammac) and recombinase activating gene (RAG)-2
      mutant mice, we have generated a novel alymphoid (B-, T-, and NK-) mouse strain
      (RAG2/gammac) suitable for NK complementation in vivo. The role of the c-abl
      proto-oncogene in murine NK cell differentiation has been addressed in
      hemopoietic chimeras generated using RAG2/gammac mice reconstituted with c-abl-/-
      fetal liver cells. The phenotypically mature NK cells that developed in the
      absence of c-abl were capable of lysing tumor targets, recognizing "missing
      self," and performing Ab-dependent cellular cytotoxicity. Taken together, these
      results exclude any essential role for c-abl in murine NK cell differentiation in
      vivo. The RAG2/gammac model thereby provides a novel approach to establish a
      genetic map of NK cell development.

PMID- 10072521
TI  - A novel role of IL-15 in the development of osteoclasts: inability to replace its
      activity with IL-2.
AB  - IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic
      progenitor cells, and macrophages. However, the role of IL-15 in
      osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15
      in rheumatoid arthritis synovial fluids suggested a possible role for this
      cytokine in the pathological destruction of bone and prompted us to determine
      whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of
      multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free
      cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in
      the early stage of osteoclast formation. The stimulation was observed even after
      treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15
      concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor
      mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent
      stimulator of TNF-alpha, its activity was not abolished by addition of anti-TNF
      alpha Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had
      no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of
      bone marrow cells before the addition of IL-15 inhibited the enhancing activity
      of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation
      of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2
      but may use components in common with IL-2R to mediate its effects.

PMID- 10072523
TI  - A tailless fas-FADD death-effector domain chimera is sufficient to execute Fas
      function in T cells but not B cells of MRL-lpr/lpr mice.
AB  - The Fas receptor delivers signals crucial for lymphocyte apoptosis through its
      cytoplasmic death domain. Several Fas cytoplasmic-associated proteins have been
      reported and studied in cell lines. So far, only Fas-associated death domain
      protein (FADD), another death domain-containing molecule has been shown to be
      essential for Fas signals in vivo. FADD is thought to function by recruiting
      caspase-8 through its death-effector domain. To test whether FADD is sufficient
      to deliver Fas signals, we generated transgenic mice expressing a chimera
      comprised of the Fas extracellular domain and FADD death-effector domain.
      Expression of this protein in lymphocytes of Fas-deficient MRL-lpr/lpr mice
      completely diminishes their T cell but not their B cell abnormalities. These
      results suggest that FADD alone is sufficient for initiation of Fas signaling in
      primary T cells, but other pathways may operate in B cells.

PMID- 10072524
TI  - Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy
      even in the presence of costimulation.
AB  - Costimulation (signal 2) has been proposed to inhibit the induction of T cell
      clonal anergy by either directly antagonizing negative signals arising from TCR
      engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in
      turn leads to proliferation and dilution of negative regulatory factors. To
      better define the cellular events that lead to the induction of anergy, we used
      the immunosuppressive agent rapamycin, which blocks T cell proliferation in late
      G1 phase but does not affect costimulation-dependent IL-2 production. Our data
      demonstrate that full T cell activation (signal 1 plus 2) in the presence of
      rapamycin results in profound T cell anergy, despite the fact that these cells
      produce copious amounts of IL-2. Similar to conventional anergy (induction by
      signal 1 alone), the rapamycin-induced anergic cells show a decrease in mitogen
      activated protein kinase activation, and these cells can be rescued by culture in
      IL-2. Interestingly, the rapamycin-induced anergic cells display a more profound
      block in IL-3 and IFN-gamma production upon rechallenge. Finally, in contrast to
      rapamycin, full T cell activation in the presence of hydroxyurea (which inhibits
      the cell cycle in early S phase) did not result in anergy. These data suggest
      that it is neither the direct effect of costimulation nor the subsequent T cell
      proliferation that prevents anergy induction, but rather the biochemical events
      that occur upon progression through the cell cycle from G1 into S phase.

PMID- 10072525
TI  - Role of a STAT binding site in the regulation of the human perforin promoter.
AB  - The pore-forming protein perforin is preferentially expressed in NK and cytotoxic
      T cells. To investigate the molecular regulation of human perforin gene
      transcription, the activity of the human perforin promoter was analyzed in human
      NK and T cell lines using various promoter fragments linked to a luciferase
      reporter gene. A core promoter was identified within 55 bp upstream of the
      transcription start site. This promoter region contains a guanine/cytosine box
      and has basal activity in YT, Kit225-k6, and Jurkat cells. A strong enhancer
      activity was identified between positions -1136 and -1076, a region that includes
      a STAT-like element. This enhancer region was active in YT cells, which have
      constitutive perforin expression and activated STAT3 protein, but not in Kit225
      k6 or Jurkat cells, which do not have constitutive perforin expression. Mutation
      of the STAT binding site resulted in a dramatic down-regulation of promoter
      activity. Electrophoretic mobility shift assays, using a probe containing the
      STAT element of the perforin promoter, indicated that this element can bind STAT3
      from YT cells. Moreover, the STAT element was shown to bind STAT5a/b induced by
      IL-2 as well as STAT1alpha induced by IL-6 in human NK cells. Together, these
      results suggest that STAT proteins play a key role in perforin gene transcription
      and provide a model by which cytokines can regulate perforin gene expression.

PMID- 10072526
TI  - Ig heavy chain expression and class switching in vitro from an allele lacking the
      3' enhancers DNase I-hypersensitive hs3A and hs1,2.
AB  - The murine Ig heavy chain (IgH) 3' regulatory region contains four enhancers:
      hs3A, hs1,2, hs3B, and hs4. Various studies have suggested a role for these
      enhancers in regulating IgH expression and class switching. Here we assess the
      role of hs3A and hs1,2 in these processes by exploiting a naturally occurring
      deletion of these enhancers from the expressed, C57BL/6 allele of the F1 pre-B
      cell line, 70Z/3. Equivalent mu expression in 70Z/3 and 18-81 (which has an
      intact 3' region) indicated that hs3A and hs1,2 were not essential for mu
      expression at the pre-B cell stage. To further examine the role of hs3A and hs1,2
      in IgH function at the plasma cell stage, we fused 70Z/3 with the plasmacytoma
      NSO. Electromobility shift assay analysis of the 70Z/3-NSO hybrids revealed a
      transcription factor complement conducive to the activation of the 3' enhancers.
      Despite the lack of enhancers, hs3A and hs1,2, the level of mu RNA and protein in
      the 70Z/3-NSO fusion hybrids was substantially elevated relative to its pre-B
      parent and comparable with that observed in a number of mu-producing spleen cell
      hybridomas. Additionally, ELISAspot assays showed that the 70Z/3-NSO hybrid
      underwent spontaneous class switching in culture to IgG1 at a frequency
      comparable with that of most hybridomas. These results indicate that hs3A and
      hs1,2 are not essential for high levels of IgH expression or for spontaneous
      class switching in a plasma cell line.

PMID- 10072527
TI  - Requirement for nuclear factor-kappaB activation by a distinct subset of CD40
      mediated effector functions in B lymphocytes.
AB  - CD40 stimulation, which is crucial for generating an effective T-dependent
      humoral response, leads to the activation of transcription factors NF-AT (nuclear
      factor of activated T cells), AP-1 (activator protein-1), and NF-kappaB (nuclear
      factor-kappaB). However, which CD40-mediated B cell functions actually require
      activation of specific transcription factors is unknown. We examined the causal
      relationship between NF-kappaB activation and CD40 effector functions by
      evaluating CD40 functions in the presence of an inducible mutant inhibitory
      kappaBalpha (IkappaBalpha) superrepressor. IkappaBalphaAA inhibited nuclear
      translocation of multiple NF-kappaB dimers without the complicating effect of
      depriving cells of NF-kappaB during development. This approach complements
      studies that use mice genetically deficient in single or multiple NF-kappaB
      subunits. Interestingly, only a subset of CD40 effector functions was found to
      require NF-kappaB activation. Both CD40-induced Ab secretion and B7-1 up
      regulation were completely abrogated by expression of IkappaBalphaAA.
      Surprisingly, up-regulation of Fas, CD23, and ICAM-1 was partially independent,
      and up-regulation of LFA-1 was completely independent, of CD40-induced NF-kappaB
      activation. For the first time, it is clear that distinct transcription factors
      are required for the dynamic regulation of CD40 functions.

PMID- 10072528
TI  - IL-5 induces IgG1 isotype switch recombination in mouse CD38-activated sIgD
      positive B lymphocytes.
AB  - Mouse B cells express CD38, whose ligation by anti-CD38 Ab induces their
      proliferation and protection from apoptosis. We previously showed that
      stimulation of mouse splenic B cells with IL-5 together with CS/2, an anti-mouse
      CD38 mAb, induces production of IgG1 and IgM. Here we examined the role of IL-5
      and CS/2 in the expression of germline gamma1 transcripts and the generation of
      reciprocal products forming DNA circles as byproducts of mu-gamma1 switch
      recombination. By itself, CS/2 induced significant expression of germline gamma1
      transcripts in splenic naive B cells, whereas IL-5 neither induced nor enhanced
      germline gamma1 expression. Increased cellular content of reciprocal product,
      which is characteristic of mu-gamma1 recombination, was not observed after
      culturing B cells with CS/2, but increased reciprocal product, along with high
      levels of lgG1 secretion, was found when B cells were cultured with CS/2 plus IL
      5. Although IL-4 did not, by itself, induce mu-gamma1 recombination in B cells
      stimulated with CS/2, in conjunction with CS/2 plus IL-5, IL-4 dramatically
      enhanced sterile gamma1 transcription and IgG1 production. These results
      demonstrate that CD38 ligation induces only germline gamma1 transcription and
      that IL-5 promotes both mu-gamma1 switch recombination and lgG1 secretion in an
      IL-4-independent manner.

PMID- 10072529
TI  - NF-ATc isoforms are differentially expressed and regulated in murine T and mast
      cells.
AB  - NF of activated T cells (NF-AT) denotes a family of transcription factors that
      regulate the activation-dependent expression of many immunologically important
      proteins. At least four distinct genes encode the various family members, and
      several isoforms of these have been identified as well. The overlapping
      expression patterns and similar in vitro binding and trans-activation activities
      on various promoter elements of NF-AT-regulated genes suggest some redundancy in
      the function of these proteins. However, the phenotypic analysis of NF-AT
      deficient mice supports the idea that there are tissue- and gene-specific
      functions as well. In this study we have characterized the expression of NF-AT
      cDNAs in murine mast cells. The majority of clones identified correspond to two
      NF-ATc isoforms that differ only in their amino-terminal sequence. Despite
      minimal discrepancies in the coding region, there are striking tissue- and cell
      type-specific differences in isoform expression patterns. Detection of NF
      ATc.alpha mRNA is strictly dependent on cell activation signals in both T and
      mast cell lines. In contrast, the beta isoform is expressed at very low
      constitutive levels in both cell types but is only up-regulated in response to
      mast cell activation signals delivered through the FcepsilonRI or via calcium
      ionophores. These results demonstrate another level of regulation within the NF
      AT family that can contribute to cell type-specific gene expression.

PMID- 10072530
TI  - Role of innate and adaptive immunity in the outcome of primary infection with
      Chlamydia pneumoniae, as analyzed in genetically modified mice.
AB  - Infection with Chlamydia pneumoniae is a common cause of acute respiratory
      disease in man and is also associated with atherosclerotic cardiovascular
      disorder. Herein, we have compared bacterial load and immune parameters of C.
      pneumoniae-infected mice genomically lacking T cell coreceptors, cytokine
      receptors, or cytotoxic effector molecules. A protective role for CD8+ cells is
      shown by the enhanced severity of infection of CD8-/- or TAP-1-/-/beta2
      microglobulin -/- mice. CD8+ cells hindered a parasite growth-promoting role of
      CD4+ T cells, as indicated by the higher sensitivity to early infection of CD8-/-
      than CD4-/-/CD8-/- mice, which was further confirmed in experiments in which SCID
      mice were reconstituted with either CD4+ or CD4+ plus CD8+ T cells.
      Interestingly, CD4+ T cells played a dual role, detrimental early (14 and 24
      days) after infection but protective at later time points (60 days after
      infection). The CD8+ T cell protection was perforin independent. The early
      deleterious role of CD4+ in the absence of CD8+ T cells was associated with
      enhanced IL-4 and IL-10 mRNA levels and delayed IFN-gamma mRNA accumulation in
      lungs. In line with this, IFN-gammaR-/- (but not TNFRp55 -/-) mice showed
      dramatically increased susceptibility to C. pneumoniae, linked to reduced
      inducible nitric oxide synthase (iNOS) mRNA accumulation, but not to diminished
      levels of specific Abs. The increased susceptibility of iNOS-/- mice indicates a
      protective role for iNOS activity during infection with C. pneumoniae. The higher
      sensitivity of IFN-gammaR-/- mice to C. pneumoniae compared with that of SCID or
      recombination-activating gene-1-/- mice suggested a relevant protective role of
      IFN-gamma-dependent innate mechanisms of protection.

PMID- 10072531
TI  - gammadelta T cells contribute to control of chronic parasitemia in Plasmodium
      chabaudi infections in mice.
AB  - During a primary infection of mice with Plasmodium chabaudi, gammadelta T cells
      are stimulated and their expansion coincides with recovery from the acute phase
      of infection in normal mice or with chronic infections in B cell-deficient mice
      (mu-MT). To determine whether the large gammadelta T cell pool observed in female
      B cell-deficient mice is responsible for controlling the chronic infection,
      studies were done using double-knockout mice deficient in both B and gammadelta
      cells (mu-MT x delta-/-TCR) and in gammadelta T cell-depleted mu-MT mice. In both
      types of gammadelta T cell-deficient mice, the early parasitemia following the
      peak of infection was exacerbated, and the chronic parasitemia was maintained at
      significantly higher levels in the absence of gammadelta T cells. The majority of
      gammadelta T cells in C57BL/6 and mu-MT mice responding to infection belonged
      predominantly to a single family of gammadelta T cells with TCR composed of
      Vgamma2Vdelta4 chains and which produced IFN-gamma rather than IL-4.

PMID- 10072532
TI  - Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-gamma in
      establishing and maintaining the tumor-dormant state.
AB  - Dormant tumor cells resistant to ablative cancer therapy represent a significant
      clinical obstacle due to later relapse. Experimentally, the murine B cell
      lymphoma (BCL1) is used as a model of tumor dormancy in mice vaccinated with the
      BCL1 Ig. Here, we used this model to explore the cellular mechanisms underlying
      dormancy. Our previous studies have demonstrated that T cell-mediated immunity is
      an important component in the regulation of tumor dormancy because Id-immune T
      cells adoptively transferred into passively immunized SCID mice challenged with
      BCL1 cells significantly increased the incidence and duration of the dormant
      state. We have extended these observations and demonstrate that CD8+, but not
      CD4+, T cells are required for the maintenance of dormancy in BCL1 Ig-immunized
      BALB/c mice. In parallel studies, the transfer of Id-immune CD8+ cells, but not
      Id-immune CD4+ cells, conferred significant protection to SCID mice passively
      immunized with nonprotective levels of polyclonal anti-Id and then challenged
      with BCL1 cells. Furthermore, the ability of CD8+ T cells to induce a state of
      dormancy in passively immunized SCID mice was completely abrogated by treatment
      with neutralizing alpha-IFN-gamma mAbs in vivo. In vitro studies demonstrated
      that IFN-gamma alone or in combination with reagents to cross-link the surface Ig
      induced both cell cycle arrest and apoptosis in a BCL1 cell line. Collectively,
      these data demonstrate a role for CD8+ T cells via endogenous production of IFN
      gamma in collaboration with humoral immunity to both induce and maintain a state
      of tumor dormancy.

PMID- 10072533
TI  - Affinity modulation of very late antigen-5 through phosphatidylinositol 3-kinase
      in mast cells.
AB  - Adhesiveness of integrins is up-regulated rapidly by a number of molecules,
      including growth factors, cytokines, chemokines, and other cell surface
      receptors, through a mechanism termed inside-out signaling. The inside-out
      signaling pathways are thought to alter integrin affinity for ligand, or cell
      surface distribution of integrin by diffusion/clustering. However, it remains to
      be clarified whether any physiologically relevant agonists induce a rapid change
      in the affinity of beta1 integrins and how ligand-binding affinity is modulated
      upon stimulation. In this study, we reported that affinity of beta1 integrin very
      late Ag-5 (VLA-5) for fibronectin was rapidly increased in bone marrow-derived
      mast cells by Ag cross-linking of FcepsilonRI. Ligand-binding affinity of VLA-5
      was also augmented by receptor tyrosine kinases when the phospholipase Cgamma
      1/protein kinase C pathway was inhibited. Wortmannin suppressed induction of the
      high affinity state VLA-5 in either case. Conversely, introduction of a
      constitutively active p110 subunit of phosphatidylinositol 3-kinase (PI 3-kinase)
      increased the binding affinity for fibronectin. Failure of a constitutively
      active Akt to stimulate adhesion suggested that the affinity modulation
      mechanisms mediated by PI 3-kinase are distinct from the mechanisms to control
      growth and apoptosis by PI 3-kinase. Taken together, our findings demonstrated
      that the increase of affinity of VLA-5 was induced by physiologically relevant
      stimuli and PI 3-kinase was a critical affinity modulator of VLA-5.

PMID- 10072534
TI  - Control of syngeneic tumor growth by activation of CD8+ T cells: efficacy is
      limited by migration away from the site and induction of nonresponsiveness.
AB  - Activation of Ag-specific CD8+ T cells in response to syngeneic tumor has been
      visualized by adoptive transfer of CD8+ T cells from OT-I mice, with a transgenic
      TCR specific for H-2Kb and an OVA peptide, into Thy-1 congenic recipients.
      Intraperitoneal challenge with E.G7, the EL-4 thymoma transfected with OVA,
      results in activation and clonal expansion of the OT-I cells in the peritoneal
      cavity and transient control of tumor growth. However, within 2 days after
      becoming activated, the OT-I cells migrate out of the peritoneal cavity into the
      spleen and lymph nodes, and tumor growth resumes in the peritoneal cavity. The OT
      I cells in lymph nodes and spleen have lytic effector activity, but exhibit split
      anergy in that they cannot proliferate in response to Ag unless exogenous IL-2 is
      provided. The failure to remain at the tumor site and continue to control tumor
      growth is not due to selection of Ag loss variants or development of suppression.
      These results suggest that effective CD8-targeted immunotherapy may depend less
      on enhancing the initial activation and more on sustaining the response at the
      appropriate location and/or reactivating cells that have left the site of tumor
      growth and become nonresponsive.

PMID- 10072535
TI  - Qualitative and quantitative requirements for CD4+ T cell-mediated antiviral
      protection.
AB  - CD4+ Th cells deliver the cognate and cytokine signals that promote the
      production of protective virus-neutralizing IgG by specific B cells and are also
      able to mediate direct antiviral effector functions. To quantitatively and
      qualitatively analyze the antiviral functions of CD4+ Th cells, we generated
      transgenic mice (tg7) expressing an MHC class II (I-Ab)-restricted TCR specific
      for a peptide derived from the glycoprotein (G) of vesicular stomatitis virus
      (VSV). The elevated precursor frequency of naive VSV-specific Th cells in tg7
      mice led to a markedly accelerated and enhanced class switching to virus
      neutralizing IgG after immunization with inactivated VSV. Furthermore, in
      contrast to nontransgenic controls, tg7 mice rapidly cleared a recombinant
      vaccinia virus expressing the VSV-G (Vacc-IND-G) from peripheral organs. By
      adoptive transfer of naive tg7 CD4+ T cells into T cell-deficient recipients, we
      found that 105 transferred CD4+ T cells were sufficient to induce isotype
      switching after challenge with a suboptimal dose of inactivated VSV. In contrast,
      naive transgenic CD4+ T cells were unable to adoptively confer protection against
      peripheral infection with Vacc-IND-G. However, tg7 CD4+ T cells that had been
      primed in vitro with VSV-G peptide were able to adoptively transfer protection
      against Vacc-IND-G. These results demonstrate that the antiviral properties of
      CD4+ T cells are governed by the differentiation status of the CD4+ T cell and by
      the type of effector response required for virus elimination.

PMID- 10072536
TI  - Coordinate involvement of invasin and Yop proteins in a Yersinia
      pseudotuberculosis-specific class I-restricted cytotoxic T cell-mediated
      response.
AB  - Yersinia pseudotuberculosis is a pathogenic enteric bacteria that evades host
      cellular immune response and resides extracellularly in vivo. Nevertheless, an
      important contribution of T cells to defense against Yersinia has been previously
      established. In this study we demonstrate that Lewis rats infected with virulent
      strains of Y. pseudotuberculosis, mount a Yersinia-specific, RT1-A-restricted,
      CD8+ T cell-mediated, cytotoxic response. Sensitization of lymphoblast target
      cells for cytolysis by Yersinia-specific CTLs required their incubation with live
      Yersinia and was independent of endocytosis. Although fully virulent Yersinia did
      not invade those cells, they attached to their surface. In contrast, invasin
      deficient strain failed to bind to blast targets or to sensitize them for
      cytolysis. Furthermore, an intact virulence plasmid was an absolute requirement
      for Yersinia to sensitize blast targets for cytolysis. Using a series of Y.
      pseudotuberculosis mutants selectively deficient in virulence plasmid-encoded
      proteins, we found no evidence for a specific role played by YadA, YopH, YpkA, or
      YopJ in the sensitization process of blast targets. In contrast, mutations
      suppressing YopB, YopD, or YopE expression abolished the capacity of Yersinia to
      sensitize blast targets. These results are consistent with a model in which
      extracellular Yersinia bound to lymphoblast targets via invasin translocate
      inside eukaryotic cytosol YopE, which is presented in a class I-restricted
      fashion to CD8+ cytotoxic T cells. This system could represent a more general
      mechanism by which bacteria harboring a host cell contact-dependent or type III
      secretion apparatus trigger a class I-restricted CD8+ T cell response.

PMID- 10072537
TI  - Experimental murine schistosomiasis in the absence of B7 costimulatory molecules:
      reversal of elicited T cell cytokine profile and partial inhibition of egg
      granuloma formation.
AB  - The granulomatous inflammation in infection with the helminth Schistosoma mansoni
      represents a cellular hypersensitivity reaction mediated by, and dependent upon,
      MHC class II-restricted CD4+ Th cells sensitized to parasite egg Ags. The current
      work examines the role and significance of the B7:CD28/CTLA-4 pathway in
      providing the costimulation necessary for the activation of these pathogenic T
      cells. In vitro T cell responses in B7-1-/- mice, 7-8 wk postinfection, were no
      different from wild-type controls, but the absence of B7-2 molecules resulted in
      a decrease in egg Ag-induced proliferation with increased IFN-gamma production.
      Both B7-1-/- and B7-2-/- mice exhibited intact granuloma formation. In contrast,
      CD4+ Th cells from B7-1/2 double-deficient mice displayed a dramatic loss of
      proliferative capacity upon stimulation with egg Ag. Most strikingly, these T
      cells secreted only IFN-gamma, but not IL-4 and IL-10, a pattern entirely
      opposite to that displayed by wild-type controls. Despite these major differences
      in T cell reactivity, B7-1/2-/- mice had only a limited reduction of granuloma
      size and fibrosis, without appreciable difference in cellular composition. These
      results show that substantial granuloma formation can occur under conditions of
      limited T cell expansion and restricted Th1-type cytokine production. They also
      support the notion that the combined effect of B7 signaling is not as critical
      for Th1 cell activation as it is for the development of the Th2 dominant
      environment characteristic of the evolving schistosome infection in H-2b mice.

PMID- 10072538
TI  - IFN-gamma and CD8+ T cells restore host defenses against Pneumocystis carinii in
      mice depleted of CD4+ T cells.
AB  - Host defenses against infection are profoundly compromised in HIV-infected hosts
      due to progressive depletion of CD4+ T lymphocytes and defective cell-mediated
      immunity. Although recent advances in antiretroviral therapy can dramatically
      lower HIV viral load, blood CD4+ T lymphocytes are not restored to normal levels.
      Therefore, we investigated mechanisms of host defense other than those involving
      CD4+ T lymphocytes against a common HIV-related opportunistic infection,
      Pneumocystis carinii (PC) pneumonia. Using CD4-depleted mice, which are
      permissive for chronic PC infection, we show that up-regulation of murine IFN
      gamma by gene transfer into the lung tissue results in clearance of PC from the
      lungs in the absence of CD4+ lymphocytes. This resolution of infection was
      associated with a >4-fold increase in recruited CD8+ T lymphocytes and NK cells
      into the lungs. The role of CD8+ T cells as effector cells in this model was
      further confirmed by a lack of an effect of IFN-gamma gene transfer in scid mice
      or mice depleted of both CD4+ and CD8+ T cells. Cytokine mRNA analysis revealed
      that recruited, lung-derived CD8+ T cells had greater expression of IFN-gamma
      message in animals treated with the IFN-gamma gene. These results indicate that
      CD8+ T cells are capable of clearing PC pneumonia in the absence of CD4+ T cells
      and that this host defense function of CD8+ T cells, as well as their cytokine
      repertoire, can be up-regulated through cytokine gene transfer.

PMID- 10072539
TI  - Macrophage control of herpes simplex virus type 1 replication in the peripheral
      nervous system.
AB  - After corneal infection, herpes simplex virus type 1 (HSV-1) invades sensory
      neurons with cell bodies in the trigeminal ganglion (TG), replicates briefly, and
      then establishes a latent infection in these neurons. HSV-1 replication in the TG
      can be detected as early as 2 days after corneal infection, reaches peak titers
      by 3-5 days after infection, and is undetectable by 7-10 days. During the period
      of HSV-1 replication, macrophages and gammadelta TCR+ T lymphocytes infiltrate
      the TG, and TNF-alpha, IFN-gamma, the inducible nitric oxide synthase (iNOS)
      enzyme, and IL-12 are expressed. TNF-alpha, IFN-gamma, and the iNOS product
      nitric oxide (NO) all inhibit HSV-1 replication in vitro. Macrophage and
      gammadelta TCR+ T cell depletion studies demonstrated that macrophages are the
      main source of TNF-alpha and iNOS, whereas gammadelta TCR+ T cells produce IFN
      gamma. Macrophage depletion, aminoguanidine inhibition of iNOS, and
      neutralization of TNF-alpha or IFN-gamma all individually and synergistically
      increased HSV-1 titers in the TG after HSV-1 corneal infection. Moreover,
      individually depleting macrophages or neutralizing TNF-alpha or IFN-gamma
      markedly reduced the accumulation of both macrophages and gammadelta TCR+ T cells
      in the TG. Our findings establish that after primary HSV-1 infection, the bulk of
      virus replication in the sensory ganglia is controlled by macrophages and
      gammadelta TCR+ T lymphocytes through their production of antiviral molecules TNF
      alpha, NO, and IFN-gamma. Our findings also strongly suggest that cross
      regulation between these two cell types is necessary for their accumulation and
      function in the infected TG.

PMID- 10072540
TI  - Mutations of the type A domain of complement factor B that promote high-affinity
      C3b-binding.
AB  - Factor B is a zymogen that carries the catalytic site of the complement
      alternative pathway convertases. During C3 convertase assembly, factor B
      associates with C3b and is cleaved at a single site by factor D. The Ba fragment
      is released, leaving the active complex, C3bBb. During the course of this
      process, the protease domain becomes activated. The type A domain of factor B,
      also part of Bb, is similar in structure to the type A domain of the complement
      receptor and integrin, CR3. Previously, mutations in the factor B type A domain
      were described that impair C3b-binding. This report describes "gain of function"
      mutations obtained by substituting factor B type A domain amino acids with
      homologous ones derived from the type A domain of CR3. Replacement of the betaA
      alpha1 Mg2+ binding loop residue D254 with smaller amino acids, especially
      glycine, increased hemolytic activity and C3bBb stability. The removal of the
      oligosaccharide at position 260, near the Mg2+ binding cleft, when combined with
      the D254G substitution, resulted in increased affinity for C3b and iC3b, a C3b
      derivative. These findings offer strong evidence for the direct involvement of
      the type A domain in C3b binding, and are suggestive that steric effects of the
      D254 sidechain and the N260-linked oligosaccharide may contribute to the
      regulation of ligand binding.

PMID- 10072541
TI  - IL-12 gene as a DNA vaccine adjuvant in a herpes mouse model: IL-12 enhances Th1
      type CD4+ T cell-mediated protective immunity against herpes simplex virus-2
      challenge.
AB  - IL-12 has been shown to enhance cellular immunity in vitro and in vivo. Recent
      reports have suggested that combining DNA vaccine approach with immune
      stimulatory molecules delivered as genes may significantly enhance Ag-specific
      immune responses in vivo. In particular, IL-12 molecules could constitute an
      important addition to a herpes vaccine by amplifying specific immune responses.
      Here we investigate the utility of IL-12 cDNA as an adjuvant for a herpes simplex
      virus-2 (HSV-2) DNA vaccine in a mouse challenge model. Direct i.m. injection of
      IL-12 cDNA induced activation of resting immune cells in vivo. Furthermore,
      coinjection with IL-12 cDNA and gD DNA vaccine inhibited both systemic gD
      specific Ab and local Ab levels compared with gD plasmid vaccination alone. In
      contrast, Th cell proliferative responses and secretion of cytokines (IL-2 and
      IFN-gamma) and chemokines (RANTES and macrophage inflammatory protein-1alpha)
      were significantly increased by IL-12 coinjection. However, the production of
      cytokines (IL-4 and IL-10) and chemokine (MCP-1) was inhibited by IL-12
      coinjection. IL-12 coinjection with a gD DNA vaccine showed significantly better
      protection from lethal HSV-2 challenge compared with gD DNA vaccination alone in
      both inbred and outbred mice. This enhanced protection appears to be mediated by
      CD4+ T cells, as determined by in vivo CD4+ T cell deletion. Thus, IL-12 cDNA as
      a DNA vaccine adjuvant drives Ag-specific Th1 type CD4+ T cell responses that
      result in reduced HSV-2-derived morbidity as well as mortality.

PMID- 10072542
TI  - Effect of nitric oxide donors on oxygen-dependent cytotoxic responses mediated by
      neutrophils.
AB  - We analyzed the effect of nitric oxide (NO) on oxygen-dependent cytotoxic
      responses mediated by neutrophils against unopsonized erythrocytes using three NO
      donors: S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP), and
      sodium nitroprusside (SNP). Neutrophils were treated with these compounds for 1-2
      min at 37 degrees C and cytotoxicity was then triggered in the presence of NO
      donors by precipitating immune complexes, aggregated IgG, the chemotactic peptide
      FMLP, or opsonized zymosan. GSNO induced, in all cases, a marked increase in
      cytotoxic responses, while SNAP moderately increased cytotoxicity triggered by
      immune complexes, aggregated IgG, or Z, opsonized zymosen, without modifying
      those responses induced by FMLP. By contrast, SNP dramatically suppressed
      cytotoxicity triggered by all of the stimuli assessed. The enhancing effects
      mediated by GSNO and SNAP did not depend on the stimulation of guanylyl cyclase
      and were prevented by the NO scavengers hemoglobin and PTIO (2-phenyl-4,4,5,5
      tetramethyl-imidazoline-1-oxyl 3-oxide). The inhibitory activity of SNP, on the
      other hand, was not prevented by NO scavengers, suggesting that it cannot be
      ascribed to the release of NO. In another set of experiments, neutrophils were
      pretreated with GSNO or SNAP for different times. Then cells were washed to
      remove NO donors from the culture medium, and cytotoxicity was triggered by
      different stimuli. It was found that neutrophils must be pretreated with NO
      donors for at least 4 h to increase cytotoxic responses, and pretreatment for
      longer periods (i.e., 8 or 18 h) further increased cytotoxicity. Not only
      cytotoxic responses, but also the production of O2- and H2O2, and the release of
      myeloperoxidase were increased under these conditions.

PMID- 10072543
TI  - Bacterial lipopolysaccharide causes rapid shedding, followed by inhibition of
      mRNA expression, of the IL-1 type II receptor, with concomitant up-regulation of
      the type I receptor and induction of incompletely spliced transcripts.
AB  - The IL-1 type I receptor (IL-1RI) is part of a signaling complex together with
      the IL-1R accessory protein, whereas available information is consistent with a
      "decoy" model of function for the IL-1 type II receptor (IL-1RII). The present
      study was designed to investigate the effect of bacterial LPS on IL-1R in human
      monocytes. LPS causes rapid release of the IL-1RII, an effect blocked by a
      metalloprotease inhibitor. Subsequently, LPS-treated monocytes showed a drastic
      reduction of IL-1RII mRNA. In contrast, LPS induced IL-1RI and, to a lesser
      extent, IL-1AcP expression. LPS-induced augmented expression of the canonical 5
      kb IL-1RI mRNA was accompanied by the appearance of 2.4-kb IL-1RI transcripts.
      The use of probes representative of different regions of the IL-1RI mRNA, as well
      as cDNA cloning, revealed that the 2.4-kb inducible band includes incompletely
      spliced, polyadenylated transcripts potentially encoding truncated versions of
      the receptor. The observation that the prototypic proinflammatory molecule LPS
      has divergent effects on IL-1Rs, with inhibition of IL-1RII and stimulation of IL
      1RI and IL-1R accessory protein, is consistent with the view that these molecules
      subserve opposite functions in the pathophysiology of the IL-1 system. The rapid
      shedding of IL-1RII by monocytes early in recruitment may serve to buffer the
      systemic action of IL-1 leaking from sites of inflammation. This early event,
      followed by prolonged inhibition of IL-1RII expression and up-regulation of IL
      1RI, may render monocytes more responsive to IL-1 at sites of inflammation.

PMID- 10072544
TI  - Selective regulation of cytokine induction by adenoviral gene transfer of
      IkappaBalpha into human macrophages: lipopolysaccharide-induced, but not zymosan
      induced, proinflammatory cytokines are inhibited, but IL-10 is nuclear factor
      kappaB independent.
AB  - Macrophages are the major cytokine producers in chronic inflammatory diseases,
      but the biochemical pathways regulating cytokine production are poorly
      understood. This is because genetic tools to dissect signaling pathways cannot be
      used in macrophages because of difficulties in transfection. We have developed an
      adenoviral technique to achieve high efficiency gene delivery into macrophages
      and recently showed that spontaneous TNF-alpha production in rheumatoid arthritis
      joint cells, chiefly from macrophages, is 75% blocked by adenoviral transfer of
      IkappaBalpha. In this report we use the same adenovirus to investigate whether
      the production of a number of proinflammatory cytokines (e.g., TNF-alpha, IL
      1beta, IL-6, and IL-8) from human macrophages depends on NF-kappaB. While the
      cytokine response to certain inducers, such as LPS, PMA, and UV light, is blocked
      by overexpression of IkappaBalpha, the response to zymosan is not. In contrast,
      anti-inflammatory mediators (IL-10 and IL-1 receptor antagonist) induced by LPS
      are only marginally inhibited by IkappaBalpha excess. These studies demonstrate
      several new points about macrophage cytokine production. First, there is
      heterogeneity of mechanisms regulating both the proinflammatory and anti
      inflammatory cytokines within populations of a single cell type. In addition, the
      results confirm the utility of the adenoviral technique for functional analysis
      of cytokine induction. The results also confirm that there are autocrine and
      paracrine interactions regulating cytokine synthesis within a single cell type.
      The selectivity of NF-kappaB blockade for proinflammatory but not anti
      inflammatory mediators indicates that in macrophages, NF-kappaB may be a good
      target for the treatment of chronic inflammatory diseases.

PMID- 10072545
TI  - Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3
      pathways.
AB  - To investigate eosinophil stimulation by chemokines we developed a sensitive
      assay of leukocyte shape change, the gated autofluorescence/forward scatter
      assay. Leukocyte shape change responses are mediated through rearrangements of
      the cellular cytoskeleton in a dynamic process typically resulting in a polarized
      cell and are essential to the processes of leukocyte migration from the
      microcirculation into sites of inflammation. We examined the actions of the
      chemokines eotaxin, eotaxin-2, monocyte chemoattractant protein-1 (MCP-1), MCP-3,
      MCP-4, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and IL-8 on
      leukocytes in mixed cell suspensions and focused on the responses of eosinophils
      to C-C chemokines. Those chemokines acting on CCR3 induced a rapid shape change
      in eosinophils from all donors; of these, eotaxin and eotaxin-2 were the most
      potent. Responses to MCP-4 were qualitatively different, showing marked reversal
      of shape change responses with agonist concentration and duration of treatment.
      In contrast, MIP-1alpha induced a potent response in eosinophils from a small and
      previously undescribed subgroup of donors via a non-CCR3 pathway likely to be
      CCR1 mediated. Incubation of leukocytes at 37 degrees C for 90 min in the absence
      of extracellular calcium up-regulated responses to MCP-4 and MIP-1alpha in the
      majority of donors, and there was a small increase in responses to eotaxin. MIP
      1alpha responsiveness in vivo may therefore be a function of both CCR1 expression
      levels and the regulated efficiency of coupling to intracellular signaling
      pathways. The observed up-regulation of MIP-1alpha signaling via non-CCR3
      pathways may play a role in eosinophil recruitment in inflammatory states such as
      occurs in the asthmatic lung.

PMID- 10072546
TI  - The human T cell leukemia virus type I-tax gene is responsible for the
      development of both inflammatory polyarthropathy resembling rheumatoid arthritis
      and noninflammatory ankylotic arthropathy in transgenic mice.
AB  - We previously reported that inflammatory arthropathy resembling rheumatoid
      arthritis (RA) develops among transgenic mice carrying the long terminal repeat
      (LTR)-env-pX-LTR region of human T cell leukemia virus type I (LTR-pX-Tg mice).
      Because four genes are encoded in this region, we produced transgenic mice that
      only express the tax gene to examine its role in the development of arthritis.
      Transgenic mice were produced by constructing DNAs that express the tax gene
      alone under the control of either its own LTR or CD4 enhancer/promoter and by
      microinjecting them into C3H/HeN-fertilized ova. We produced seven transgenic
      mice carrying the LTR-tax gene and nine mice carrying the CD4-tax and found that
      one of the LTR-tax-Tg mice and five of CD4-tax-Tg mice developed RA-like
      inflammatory arthropathy similar to LTR-pX-Tg mice, indicating that the tax gene
      is arthritogenic. On the other hand, the other two LTR-tax-Tg mice had ankylotic
      changes caused by new bone formation without inflammation. In these ankylotic
      mice, tax mRNA, inflammatory cytokine mRNA, and autoantibody levels except for
      TGF-beta1 level were lower than those in LTR-pX- or CD4-tax-Tg mice. These
      results show that Tax is responsible for the development of inflammatory
      arthropathy resembling RA and that this protein also causes ankylotic
      arthropathy.

PMID- 10072547
TI  - Lymphocyte migration through brain endothelial cell monolayers involves signaling
      through endothelial ICAM-1 via a rho-dependent pathway.
AB  - Lymphocyte extravasation into the brain is mediated largely by the Ig superfamily
      molecule ICAM-1. Several lines of evidence indicate that at the tight vascular
      barriers of the central nervous system (CNS), endothelial cell (EC) ICAM-1 not
      only acts as a docking molecule for circulating lymphocytes, but is also involved
      in transducing signals to the EC. In this paper, we examine the signaling
      pathways in brain EC following Ab ligation of endothelial ICAM-1, which mimics
      adhesion of lymphocytes to CNS endothelia. ICAM-1 cross-linking results in a
      reorganization of the endothelial actin cytoskeleton to form stress fibers and
      activation of the small guanosine triphosphate (GTP)-binding protein Rho. ICAM-1
      stimulated tyrosine phosphorylation of the actin-associated molecule cortactin
      and ICAM-1-mediated, Ag/IL-2-stimulated T lymphocyte migration through EC
      monolayers were inhibited following pretreatment of EC with cytochalasin D.
      Pretreatment of EC with C3 transferase, a specific inhibitor of Rho proteins,
      significantly inhibited the transmonolayer migration of T lymphocytes,
      endothelial Rho-GTP loading, and endothelial actin reorganization, without
      affecting either lymphocyte adhesion to EC or cortactin phosphorylation. These
      data show that brain vascular EC are actively involved in facilitating T
      lymphocyte migration through the tight blood-brain barrier of the CNS and that
      this process involves ICAM-1-stimulated rearrangement of the endothelial actin
      cytoskeleton and functional EC Rho proteins.

PMID- 10072548
TI  - TGF-beta does not inhibit IL-12- and IL-2-induced activation of Janus kinases and
      STATs.
AB  - The immune system is an important target for the cytokine TGF-beta1, whose
      actions on lymphocytes are largely inhibitory. TGF-beta has been reported to
      inhibit IL-12- and IL-2-induced cell proliferation and IFN-gamma production by T
      cells and NK cells; however, the mechanisms of inhibition have not been clearly
      defined. It has been suggested by some studies that TGF-beta blocks cytokine
      induced Janus kinase (JAK) and STAT activation, as in the case of IL-2. In
      contrast, other studies with cytokines like IFN-gamma have not found such an
      inhibition. The effect of TGF-beta on the IL-12-signaling pathway has not been
      addressed. We examined this and found that TGF-beta1 did not have any effect on
      IL-12-induced phosphorylation of JAK2, TYK2, and STAT4 although TGF-beta1
      inhibited IL-2- and IL-12-induced IFN-gamma production. Similarly, but in
      contrast to previous reports, we found that TGF-beta1 did not inhibit IL-2
      induced phosphorylation of JAK1, JAK3, and STAT5A. Furthermore, gel shift
      analysis showed that TGF-beta1 did not prevent activated STAT4 and STAT5A from
      binding to DNA. Our results demonstrate that the inhibitory effects of TGF-beta
      on IL-2- and IL-12-induced biological activities are not attributable to
      inhibition of activation of JAKs and STATs. Rather, our data suggest the
      existence of alternative mechanisms of inhibition by TGF-beta.

PMID- 10072549
TI  - Endogenous platelet-activating factor is critically involved in effector
      functions of eosinophils stimulated with IL-5 or IgG.
AB  - Eosinophil activation and subsequent release of inflammatory mediators are
      implicated in the pathophysiology of allergic diseases. Eosinophils are activated
      by various classes of secretagogues, such as cytokines (e.g., IL-5), lipid
      mediators (e.g., platelet-activating factor (PAF)), and Ig (e.g., immobilized
      IgG). However, do these agonists act directly on eosinophils or indirectly
      through the generation of intermediate active metabolites? We now report that
      endogenous PAF produced by activated eosinophils plays a critical role in
      eosinophil functions. Human eosinophils produced superoxide when stimulated with
      immobilized IgG, soluble IL-5, or PAF. Pretreating eosinophils with pertussis
      toxin abolished their responses to these stimuli, suggesting involvement of a
      metabolite(s) that acts on G proteins. Indeed, PAF was detected in supernatants
      from eosinophils stimulated with IgG or IL-5. Furthermore, structurally distinct
      PAF antagonists, including CV6209, hexanolamine PAF, and Y-24180 (israpafant),
      inhibited IgG- or IL-5-induced superoxide production and degranulation. Previous
      reports indicated that exogenous PAF stimulates eosinophil eicosanoid production
      through formation of lipid bodies. We found in this study that IgG or IL-5 also
      induces lipid body formation and subsequent leukotriene C4 production mediated by
      endogenous PAF. Finally, inhibition of cytosolic phospholipase A2, one of the key
      enzymes involved in PAF synthesis, attenuated both PAF production and effector
      functions of eosinophils. These findings suggest that endogenous PAF plays
      important roles in eosinophil functional responses to various exogenous stimuli,
      such as cytokines and Igs. Therefore, inhibition of PAF synthesis or action may
      be beneficial for the treatment of eosinophilic inflammation.

PMID- 10072550
TI  - Ligation of ICAM-1 on endothelial cells leads to expression of VCAM-1 via a
      nuclear factor-kappaB-independent mechanism.
AB  - ICAM-1 is an Ig-like cell adhesion molecule expressed by several cell types,
      including the endothelium. Cross-linking of ICAM-1 on the surface of different
      cell types has previously been shown to cause an increase in cellular activation
      within the cytoplasm. In this study, we have compared signaling events following
      ligation of ICAM-1 by cross-linking with mAbs with events after activation of
      HUVEC by TNF. ICAM-1 cross-linking caused activation of Erk-1 and the AP-1
      transcription factor complex, without any increase in NF-kappaB activity, in
      contrast to TNF stimulation. Transcription of VCAM-1 mRNA was observed by reverse
      transcriptase PCR after ICAM-1 cross-linking, with no associated transcription of
      E-selectin. This was reflected by the presence of VCAM-1 protein after
      immunoprecipitation, without E-selectin expression, in ICAM-1 cross-linked cells.
      In contrast, mRNA and protein for both VCAM-1 and E-selectin were observed in TNF
      treated HUVEC, as expected. Addition of the MEK (MAP/Erk kinase) inhibitor
      PD98059 reduced expression of VCAM-1 after ICAM-1 cross-linking, suggesting that
      the Erk pathway is involved in ICAM-1-mediated VCAM-1 expression. In conclusion,
      ICAM-1-induced expression of VCAM-1 represents a pathway for adhesion molecule up
      regulation that is distinct from the TNF-induced pathway. It may be similar to
      the IL-4 pathway or it may represent a novel pathway.

PMID- 10072551
TI  - IL-5 and eosinophils are essential for the development of airway
      hyperresponsiveness following acute respiratory syncytial virus infection.
AB  - Viral respiratory infections can cause bronchial hyperresponsiveness and
      exacerbate asthma. In mice, respiratory syncytial virus (RSV) infection, which
      induces an immune response dominated by IFN-gamma, results in airway
      hyperresponsiveness (AHR) and eosinophil influx into the airways, both of which
      are prevented by pretreatment with anti-IL-5 Ab. To delineate the role of IL-5,
      IL-4, and IFN-gamma in the development of RSV-induced AHR and lung eosinophilia,
      we tested the ability of mice deficient in each of these cytokines to develop
      these symptoms of RSV infection. Mice deficient in either IL-5, IL-4, or IFN
      gamma were administered infectious RSV intranasally, and 6 days later, airway
      responsiveness to inhaled methacholine was assessed by barometric body
      plethysmography, and numbers of lung eosinophils and production of IFN-gamma, IL
      4, and IL-5 by mononuclear cells from peribronchial lymph nodes were monitored.
      RSV infection resulted in airway eosinophilia and AHR in both IL-4- and IFN-gamma
      deficient mice, but not in IL-5-deficient mice. Reconstitution of IL-5-deficient
      mice with IL-5 restored these responses and enhanced the responses in IL-4
      deficient mice. Anti-VLA-4 (very late Ag-4) treatment prevented lung eosinophilia
      and AHR following RSV infection and IL-5 reconstitution. We conclude that in
      response to RSV, IL-5 is essential for the influx of eosinophils into the lung
      and that eosinophils in turn are critical for the development of AHR. IFN-gamma
      and IL-4 are not essential for these responses to RSV infection.

PMID- 10072552
TI  - A phosphatidylcholine-specific phospholipase C regulates activation of p42/44
      mitogen-activated protein kinases in lipopolysaccharide-stimulated human alveolar
      macrophages.
AB  - This study uses human alveolar macrophages to determine whether activation of a
      phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) is linked to
      activation of the p42/44 (ERK) kinases by LPS. LPS-induced ERK kinase activation
      was inhibited by tricyclodecan-9-yl xanthogenate (D609), a relatively specific
      inhibitor of PC-PLC. LPS also increased amounts of diacylglycerol (DAG), and this
      increase in DAG was inhibited by D609. LPS induction of DAG was, at least in
      part, derived from PC hydrolysis. Ceramide was also increased in LPS-treated
      alveolar macrophages, and this increase in ceramide was inhibited by D609.
      Addition of exogenous C2 ceramide or bacterial-derived sphingomyelinase to
      alveolar macrophages increased ERK kinase activity. LPS also activated PKC zeta,
      and this activation was inhibited by D609. LPS-activated PKC zeta phosphorylated
      MAP kinase kinase, the kinase directly upstream of the ERK kinases. LPS-induced
      cytokine production (RNA and protein) was also inhibited by D609. As an
      aggregate, these studies support the hypothesis that one way by which LPS
      activates the ERK kinases is via activation of PC-PLC and that activation of a PC
      PLC is an important component of macrophage activation by LPS.

PMID- 10072553
TI  - Corticotropin-releasing factor receptor 1 in mouse spleen: expression after
      immune stimulation and identification of receptor-bearing cells.
AB  - A specific polyclonal Ab against the N-terminal domain of corticotropin-releasing
      factor (CRF) receptor, type 1 (CRF-R1), was employed to an immunohistochemical
      analysis of the spleen from naive mice and mice exposed to an immune challenge.
      Cell types stained with anti-CRF-R1 Ab were identified by their nuclear shapes
      and colocalization with the cell type-specific markers ER-MP58, ER-MP20, Moma-1,
      Moma 2, anti-CD3e mAbs, and anti-Ig Ab. Only a few clusters of CRF-R1+ cells were
      found in spleen sections of naive mice at sites typical for granulopoietic
      islands. However, a 17-fold increase in the mean number of CRF-R1+ cells was
      noted within hours following a challenge of acute systemic inflammation induced
      by i.p. administration of LPS. The majority of these cells were identified as
      mature neutrophils. CRF-R1 was shown to mediate suppression of the IL-1beta
      secretion by these cells. However, at later time points a large number of
      granulocyte-macrophage precursors was strongly labeled with anti-CRF-R1 Ab.
      Western blot analysis of splenic membranes from animals treated with LPS revealed
      a m.w. of approximately 70,000 for CRF-R1. Subcellular staining patterns were
      suggestive for the predominant localization of CRF-R1 on granule membranes. CRF
      R1 mRNA was detected in spleen but not in bone marrow and peripheral blood
      leukocytes from naive mice. Thus, it was indicated that CRF-R1 was not produced
      constitutively by mature or immature neutrophils. Its production was rather
      triggered by inflammatory stimuli.

PMID- 10072554
TI  - Genetic evidence for functional redundancy of Platelet/Endothelial cell adhesion
      molecule-1 (PECAM-1): CD31-deficient mice reveal PECAM-1-dependent and PECAM-1
      independent functions.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31), a member of the Ig
      superfamily, is expressed strongly at endothelial cell-cell junctions, on
      platelets, and on most leukocytes. CD31 has been postulated to play a role in
      vasculogenesis and angiogenesis, and has been implicated as a key mediator of the
      transendothelial migration of leukocytes. To further define the physiologic role
      of CD31, we used targeted gene disruption of the CD31 gene in embryonic stem
      cells to generate CD31-deficient mice. CD31-deficient mice (CD31KO) are viable
      and born at the expected Mendelian frequency, remain healthy, and exhibit no
      obvious vascular developmental defects. In response to inflammatory challenge,
      polymorphonuclear leukocytes of CD31KO mice are arrested between the vascular
      endothelium and the basement membrane of inflammatory site mesenteric
      microvessels, confirming a role for CD31 in the migration of neutrophils through
      the subendothelial extracellular matrix. Normal numbers of leukocytes are
      recovered from inflammatory sites in CD31KO mice, however, suggesting that the
      defect in leukocyte migration across basal lamina observed in the absence of CD31
      may be compensated for by the use of other adhesion molecules, or possibly an
      increased rate of migration. Homing of T lymphocytes in vivo is normal, and
      CD31KO mice are able to mount a cutaneous hypersensitivity response normally. In
      addition, CD31-mediated homophilic adhesion does not appear to play a role in
      platelet aggregation in vitro. This study provides genetic evidence that CD31 is
      involved in transbasement membrane migration, but does not play an obligatory
      role in either vascular development or leukocyte migration.

PMID- 10072555
TI  - Ethanol-induced macrophage apoptosis: the role of TGF-beta.
AB  - Both clinical and laboratory reports indicate that ethanol addicts are prone to
      recurrent infections. We hypothesize that ethanol promotes macrophage apoptosis,
      thus compromising the efficiency of the mononuclear phagocyte system in dealing
      with infection. We studied the effect of ethanol on macrophage apoptosis. Human
      monocytes isolated from healthy subjects after an alcohol drinking binge showed
      enhanced apoptosis (before, 1.2 +/- 0.3% vs after, 28.4 +/- 3.7% apoptotic
      cells/field). Peritoneal macrophages harvested from ethanol-treated rats also
      showed increased (p < 0.0001) apoptosis. DNA isolated from peritoneal macrophages
      of ethanol-treated rats displayed integer multiples of 200 base pairs (ladder
      pattern). Furthermore, macrophages harvested from ethanol-treated rats had an
      enhanced expression as well as accumulation of TGF-beta. In in vitro studies,
      ethanol promoted apoptosis of human monocytes as well as rat peritoneal
      macrophages. In addition, ethanol enhanced apoptosis of murine macrophages (J774)
      in a time-dependent manner. The ethanol-induced apoptosis was amplified by LPS
      and partly attenuated (p < 0.001) by anti-TGF-beta Ab. TGF-beta also promoted
      macrophage apoptosis in a dose-dependent manner. Moreover, ethanol enhanced TGF
      beta protein production by macrophages. These results indicate that ethanol
      promotes macrophage apoptosis. This effect of ethanol seems to be partly mediated
      through the generation of TGF-beta by macrophages.

PMID- 10072556
TI  - Macrophage inflammatory protein-2 is required for neutrophil passage across the
      epithelial barrier of the infected urinary tract.
AB  - IL-8 is a major human neutrophil chemoattractant at mucosal infection sites. This
      study examined the C-X-C chemokine response to mucosal infection, and,
      specifically, the role of macrophage inflammatory protein (MIP)-2, one of the
      mouse IL-8 equivalents, for neutrophil-epithelial interactions. Following
      intravesical Escherichia coli infection, several C-X-C chemokines were secreted
      into the urine, but only MIP-2 concentrations correlated to neutrophil numbers.
      Tissue quantitation demonstrated that kidney MIP-2 production was triggered by
      infection, and immunohistochemistry identified the kidney epithelium as a main
      source of MIP-2. Treatment with anti-MIP-2 Ab reduced the urine neutrophil
      numbers, but the mice had normal tissue neutrophil levels. By
      immunohistochemistry, the neutrophils were found in aggregates under the pelvic
      epithelium, but in control mice the neutrophils crossed the urothelium into the
      urine. The results demonstrate that different chemokines direct neutrophil
      migration from the bloodstream to the lamina propria and across the epithelium
      and that MIP-2 serves the latter function. These findings suggest that
      neutrophils cross epithelial cell barriers in a highly regulated manner in
      response to chemokines elaborated at this site. This is yet another mechanism
      that defines the mucosal compartment and differentiates the local from the
      systemic host response.

PMID- 10072557
TI  - Strain-dependent induction of allergic sensitization caused by peanut allergen
      DNA immunization in mice.
AB  - To investigate the potential application of allergen gene immunization in the
      modulation of food allergy, C3H/HeSn (C3H) mice received i.m. injections of pAra
      h2 plasmid DNA encoding one of the major peanut allergens, Ara h2. Three weeks
      following pDNA immunization, serum Ara h2-specific IgG2a, IgG1, but not IgE, were
      increased significantly in a dose-dependent manner. IgG1 was 30-fold higher in
      multiply compared with singly immunized mice. Ara h2 or peanut protein injection
      of immunized mice induced anaphylactic reactions, which were more severe in
      multiply immunized mice. Heat-inactivated immune serum induced passive cutaneous
      anaphylaxis, suggesting that anaphylaxis in C3H mice was mediated by IgG1. IgG1
      responses were also induced by intradermal injection of pAra h2, and by i.m.
      injection of pOMC, the plasmid DNA encoding the major egg allergen protein,
      ovomucoid. To elucidate whether the pDNA immunization-induced anaphylaxis was a
      strain-dependent phenomenon, AKR/J and BALB/c mice also received multiple i.m.
      pAra h2 immunizations. Injection of peanut protein into these strains at weeks 3
      or 5 following immunization did not induce reactions. Although IgG2a was
      increased significantly from week 2 in AKR/J mice and from week 4 in BALB/c mice
      and remained elevated for at least 6 wk, no IgG1 or IgE was detected. These
      results indicate that the type of immune responses to pDNA immunization in mice
      is strain dependent. Consequently, models for studying human allergen gene
      immunization require careful selection of suitable strains. In addition, this
      suggests that similar interindividual variation is likely in humans.

PMID- 10072558
TI  - Plasma cell development in synovial germinal centers in patients with rheumatoid
      and reactive arthritis.
AB  - Plasma cells are found surrounding the inflammatory infiltrates of macrophages,
      T, and B cells in the synovial tissue of patients with rheumatoid and reactive
      arthritis. This characteristic arrangement suggests that in the synovial tissue
      CD20+ B cells differentiate into plasma cells. To examine clonal relationships,
      we have used micromanipulation to separately isolate CD20+ B cells and plasma
      cells from single infiltrates. DNA was extracted, and from both populations the
      VH/VL gene repertoires was determined. The data show that in the inflamed
      synovial tissue activated B cells are clonally expanded. During proliferation in
      the network of follicular dendritic cells, V gene variants are generated by the
      hypermutation mechanism. Surprisingly, we do not find identical rearrangements
      between CD20+ B cells and plasma cells. Nevertheless, the finding of clonally
      related plasma cells within single infiltrates suggests that these cells
      underwent terminal differentiation in the synovial tissue. These results indicate
      that B cell differentiation in the synovial tissue is a dynamic process. Whereas
      CD20+ B cells may turnover rapidly, plasma cells may well be long lived and thus
      accumulate in the synovial tissue. The analysis of individual B cells recovered
      from synovial tissue opens a new way to determine the specificity of those cells
      that take part in the local immune reaction. This will provide new insights into
      the pathogenesis of chronic inflammatory diseases like rheumatoid or reactive
      arthritis.

PMID- 10072559
TI  - EBV structural antigens, gp350 and gp85, as targets for ex vivo virus-specific
      CTL during acute infectious mononucleosis: potential use of gp350/gp85 CTL
      epitopes for vaccine design.
AB  - For many years, EBV vaccine development efforts have concentrated on the use of
      structural Ag, gp350, and have been directed toward Ab-mediated blocking virus
      attachment to the target cell. There is increasing evidence to suggest that the
      development of neutralizing Abs in vaccinated animals does not always correlate
      with protection; nevertheless, it has been postulated that gp350-specific T cell
      mediated immune responses may have an effector role in protection. This
      hypothesis has largely remained untested. In the present study, we demonstrate
      that CTL from acute infectious mononucleosis patients display strong ex vivo
      reactivity against the EBV structural Ags, gp85 and gp350. Moreover, long-term
      follow up studies on infectious mononucleosis-recovered individuals showed that
      these individuals maintain gp350- and gp85-specific memory CTL, albeit at low
      levels, in the peripheral blood. These results strongly suggest that CTL specific
      for EBV structural proteins may play an important role in the control of EBV
      infection during acute infection. More importantly, we also show that prior
      immunization of HLA A2/Kb transgenic mice with gp350 and gp85 CTL epitopes
      induced a strong epitope-specific CTL response and afforded protection against
      gp85- or gp350-expressing vaccinia virus challenge. These results have important
      implications for future EBV vaccine design and provides evidence, for the first
      time, that CTL epitopes from EBV structural proteins may be used for establishing
      strong antiviral immunity against EBV infection.

PMID- 10072560
TI  - HIV-1-specific CTL responses primed in vitro by blood-derived dendritic cells and
      Th1-biasing cytokines.
AB  - Vaccine strategies designed to elicit strong cell-mediated immune responses to
      HIV Ags are likely to lead to protective immunity against HIV infection.
      Dendritic cells (DC) are the most potent APCs capable of priming both MHC class I
      and II-restricted, Ag-specific T cell responses. Utilizing a system in which
      cultured DC from HIV-seronegative donors were used as APC to present HIV-1 Ags to
      autologous T cells in vitro, the strength and specificity of primary HIV-specific
      CTL responses generated to exogenous HIV-1 Nef protein as well as intracellularly
      expressed nef transgene product were investigated. DC expressing the nef gene
      were able to stimulate Nef-specific CTL, with T cells from several donors
      recognizing more than one epitope restricted by a single HLA molecule. Primary
      Nef-specific CTL responses were also generated in vitro using DC pulsed with Nef
      protein. T cells primed with Nef-expressing DC (via protein or transgene) were
      able to lyse MHC class I-matched target cells pulsed with defined Nef epitope
      peptides as well as newly identified peptide epitopes. The addition of Th1
      biasing cytokines IL-12 or IFN-alpha, during priming with Nef-expressing DC,
      enhanced the Nef-specific CTL responses generated using either Ag-loading
      approach. These results suggest that this in vitro vaccine model may be useful in
      identifying immunogenic epitopes as vaccine targets and in evaluating the effects
      of cytokines and other adjuvants on Ag-specific T cell induction. Successful
      approaches may provide information important to the development of prophylactic
      HIV vaccines and are envisioned to be readily translated into clinical DC-based
      therapeutic vaccines for HIV-1.

PMID- 10072561
TI  - Induction of autoimmunity by multivalent immunodominant and subdominant T cell
      determinants of La (SS-B).
AB  - We investigated the consequences of altering the form and valence of defined
      autodeterminants on the initiation and spreading of experimentally induced La/Ro
      autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following
      immunization of healthy mice with defined immunodominant and subdominant T cell
      determinants of the La (SS-B) autoantigen synthesized as either monomeric or
      multiple antigenic (MAP) peptides. Abs to mouse La (mLa) developed faster and
      were of higher titer in mice immunized with the subdominant mLa25-44 MAP compared
      with mice immunized with the 25-44 monomer. Rapid intermolecular spreading of the
      autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa25
      44 MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice
      immunized and boosted with the known tolerogenic mLa287-301 determinant delivered
      as monomeric peptide failed to develop Abs to either intact mLa or mLa287-301
      peptide. However, immunization with the multivalent mLa287-301 peptide led to the
      rapid production of high titer mLa autoantibodies associated with a proliferative
      T cell response to the mLa287-301 peptide. The data suggested that the enhanced
      immunogenicity of MAPs was not due to augmented Ag presentation or T cell
      stimulation. However, MAP-, but not monomer peptide-, containing immune complexes
      were potent substrates for Ab-dependent fixation of complement. These results
      demonstrate that the form of Ag responsible for inducing autoimmunity can
      profoundly influence the nature and magnitude of the immune response. Thus,
      molecular mimicry of tolerogenic and nontolerogenic self determinants might
      trigger autoimmunity under conditions of altered valence.

PMID- 10072562
TI  - Altered helper T lymphocyte function associated with chronic hepatitis B virus
      infection and its role in response to therapeutic vaccination in humans.
AB  - Theradigm-hepatitis B virus (HBV) is an experimental lipopeptide vaccine designed
      to stimulate induction of HBV-specific CTL responses in HLA-A2 individuals.
      Previous studies had demonstrated high immunogenicity in healthy volunteers, but
      comparatively weak CTL responses in chronically infected HBV patients. Herein, we
      examined helper T lymphocyte (HTL) responses in chronically infected patients.
      Despite normal proliferation and IL-2 secretion, IL-12 and IFN-gamma secretion in
      vitro in response to the vaccine was reduced compared with healthy volunteers. A
      similar pattern of cytokine secretion was observed following mitogen stimulation,
      suggesting a general altered balance of Th1/Th2 responses. Further analysis
      indicated that HTL recall responses to whole tetanus toxoid protein were reduced
      in chronically infected subjects, and reduced responsiveness correlated with the
      outcome of Theradigm-HBV immunization. Finally, experiments in HBV transgenic
      mice indicated that the nonnatural Pan DR HTL epitope, PADRE, is capable of
      inducing high levels of IFN-gamma secretion and that its inclusion in a
      lipopeptide incorporating an immunodominant Ld-restricted CTL epitope resulted in
      breaking tolerance at the CTL level. Overall, our results demonstrate an
      alteration in the quality of HTL responses induced in chronically infected HBV
      patients and suggest that use of a potent HTL epitope may be important to
      overcome CTL tolerance against specific HBV Ags.

PMID- 10072563
TI  - Genetic analysis of disease subtypes and sexual dimorphisms in mouse experimental
      allergic encephalomyelitis (EAE): relapsing/remitting and monophasic
      remitting/nonrelapsing EAE are immunogenetically distinct.
AB  - Experimental allergic encephalomyelitis (EAE) is the principal animal model of
      multiple sclerosis (MS), the major inflammatory disease of the central nervous
      system. Murine EAE is generally either an acute monophasic or relapsing disease.
      Because the clinical spectrum of MS is more diverse, the limited range of disease
      subtypes observed in EAE has raised concern regarding its relevance as a model
      for MS. During the generation of a large F2 mapping population between the EAE
      susceptible SJL/J and EAE-resistant B10.S/DvTe inbred lines, we identified four
      distinct subtypes of murine EAE resembling clinical subtypes seen in MS. We
      observed acute progressive, chronic/nonremitting, remitting/relapsing, and
      monophasic remitting/nonrelapsing EAE. An additional subtype, benign EAE, was
      identified after histologic examination revealed that some mice had inflammatory
      infiltrates of the central nervous system, but did not show clinical signs of
      EAE. Genome exclusion mapping was performed to identify the loci controlling
      susceptibility to each disease subtype. We report three novel EAE-modifying loci
      on chromosomes 16, 7, and 13 (eae11-13, respectively). Additionally, unique loci
      with gender-specific effects govern susceptibility to remitting/relapsing (eae12)
      and monophasic remitting/nonrelapsing (eae7 and 13) EAE.

PMID- 10072564
TI  - The UV-responsive melanocyte system: a peripheral network for photoperiodic time
      measurements. a function of indoleamine expression.
AB  - Earlier studies indicate the involvement of indoleamines in the melanocyte
      photoresponse and cell cycle. In this study whole skin organ cultures were done
      to study the location of indoleamine expression during the photoresponse. Whole
      skin organ cultures from marginal zone vitiligo were incubated in MEM containing
      adriamycin and exposed to varying pulses of UV at 2 h of incubation. The G2 phase
      marginal melanocytes show increasing dendricity in response to increasing UV
      exposure at 3 h of incubation. On immunohistochemical staining for serotonin and
      melatonin, it is observed that both are positive in these melanocytes. The
      proportion of serotonin-positive melanocytes rises with increasing UV exposure
      while that of melatonin positivity rises with decreasing UV exposure, thus
      simulating the pineal response to light entrainment. This is due to
      photoinhibition of enzymes converting serotonin to melatonin. This study shows
      that the melanocytes in the skin can serve as the peripheral neural net for
      photoperiodic time measurements - the biological calendar.

PMID- 10072565
TI  - Histomorphology of an ileal orthotopic neobladder: 24 Year's follow-up.
AB  - No morphological data are so far available about long-term (over 15 years)
      adaptation and outcome of ileal neobladders. In this single case report we have
      studied a 72-year-old man who underwent reconstruction of an ileal neobladder 24
      years ago. The ileal epithelium shows changes toward a colonic aspect with
      villous atrophy and increased goblet cell number although, as in normal ileum,
      sialomucins are the most abundant secretory products. Neuroendocrine cells are
      reduced to a few elements of a single morphological class. Even in the presence
      of a low apoptotic rate reduced cell proliferation causes mucosal thinning. These
      adaptive mechanisms grant an excellent clinical and functional result even beyond
      20 years after surgery. It is suggested that ileal neobladder can constitute an
      important model for the study of epithelial differentiation control.

PMID- 10072566
TI  - Innervation pattern of different cartilaginous tissues in the rat.
AB  - BACKGROUND: The innervation of skeletal tissues by sensory nerves is poorly
      understood - especially of nerve fibres which reach into the bony and
      cartilaginous tissue. METHODS: Samples of rat cartilaginous tissues from
      different locations (knee joint, vertebral column, temporomandibular joint) were
      fixed by perfusion and decalcified. The distribution of protein gene product
      (PGP) 9.5-, calcitonin gene-related peptide (CGRP)- and tachykinin (TK)
      immunoreactive axons was analysed using fluorescence immunohistochemistry.
      RESULTS: Nerve fibres were detected in the outer regions of the hyaline cartilage
      of the knee joint, in the hyaline cartilage of the vertebral body, in the
      fibrocartilage of the intervertebral disc and menisci, and in the articular disc
      of the temporomandibular joint. Predominantly, they were found to be CGRP
      immunoreactive. CONCLUSION: The neuropeptidergic innervation of the hyaline
      cartilage in different locations and the presence of nerve fibres in the
      fibrocartilage might indicate that in addition to the classical neuronal afferent
      and efferent pathway these fibres may also mediate trophic actions like tissue
      adaptation and repair.

PMID- 10072567
TI  - Distribution of NADPH-diaphorase and nitric oxide synthase in the trigeminal
      ganglion and mesencephalic trigeminal nucleus of the cat. A histochemical and
      immunohistochemical study.
AB  - The trigeminal ganglion (TrG) and mesencephalic trigeminal nucleus (MTN) neurons
      are involved in the transmission of orofacial sensory information. The presence
      of nitric oxide (NO), a putative neurotransmitter substance in the nervous
      system, was examined in the cat TrG and MTN using nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) histochemistry and nitric oxide
      synthase (NOS) immunohistochemistry. In the TrG, where the majority of the
      trigeminal primary afferent perikarya are located, most of the intensely NADPH-d/
      NOS-stained cells were small in size and distributed randomly throughout the
      ganglion. The medium-sized neurons were moderately stained. A plexus of
      pericellular varicose arborizations around large unstained ganglion cells and
      densely stained fibers in-between could also be observed. In the caudal part of
      the MTN, both NADPH-d activity and NOS immunoreactivity was present in MTN
      neurons. In addition, a few scattered NADPH-d/NOS-containing neurons were found
      in the mesencephalic-pontine junction part of the nucleus. In contrast, only
      nerve fibers and their terminals were present at a more rostral level in the mid-
      and rostral MTN. MTN neuronal perikarya were enveloped in fine basket-like NADPH
      d/ NOS-positive networks. Differential expression patterns of NOS and its marker
      NADPH-d suggest that trigeminal sensory information processing in the cat MTN is
      controlled by nitrergic input through different mechanisms. We introduce the
      concept that NO can act as a neurotransmitter in mediating nociceptive and
      proprioceptive information from periodontal mechanoreceptors but may also
      participate in modulating the activity of jaw-closing muscle afferent MTN
      neurons.

PMID- 10072568
TI  - An additional bone in the sclera of the eyes of owls and the common potoo
      (Nictibius griseus) and its role in the contraction of the nictitating membrane.
AB  - Morphometric, anatomical and histological examinations were made in 10 species of
      owls of the families Tytonidae and Strigidae and compared with the eyes of other
      species of nocturnal birds including common potoo (Nictibiidae) and three species
      of nightjars (Caprimulgidae) and two diurnal species: the roadside hawk
      (Accipitridae) and the domestic duck (Anatidae). In owls and the common potoo the
      nictitating membrane is situated on the dorsal edge of the eye. In these birds,
      the scleral ring bears an additional, previously undescribed bone of various
      forms and dimensions (1.4-6.8 mm of length and 0.8-3.3 mm of width), located on
      the trajectory of the tendon of the pyramidal muscle which is attached to the
      nictitating membrane. This bone has a groove that encloses the tendon of the
      pyramidal muscle, preventing it from separating from the sclera during
      contraction, as well as diverting the trajectory of the tendon to impede it from
      projecting itself over the cornea. In the ferruginous pygmy owl, Nacunda
      nighthawk, Pauraque, scissor-tailed nightjar, roadside hawk and domestic duck the
      additional bone was not seen. Based on the morphofunctional characteristics of
      the bone, we suggest that this bone should be named the scleral sesamoid bone.

PMID- 10072569
TI  - Radial fibre proportions in human knee joint menisci. Measurement by scanning
      optical microscopy.
AB  - The proportions of medial and lateral knee joint menisci represented by radially
      orientated collagen (COL) were measured in 42 specimens from 24 hospital patients
      examined post-mortem. Images of the fibre bundles were obtained by the 488-nm
      laser confocal scanning of hydrated, fixed radial blocks taken from the anterior,
      middle and posterior regions of the menisci after staining with picro-Sirius red.
      Measurements of the percentage of each image occupied by fluorescent, doubly
      refractile COL were made by means of a Kontron IBAS image analyser, after
      interactive segmentation. In areas adjoining the outer, lateral parts of both the
      medial and lateral menisci, the proportion of all samples identified as radial
      COL was 7.56 +/- 0.28%. The corresponding figure for areas near the inner, medial
      edges of the menisci was 17.80 +/- 0.80%. However, no relationship was
      demonstrable between age and sex and meniscal radial fibre optical density, and
      there was no difference between the proportion of radial fibres in the anterior,
      middle or posterior regions.

PMID- 10072570
TI  - Differences in the iliolumbar ligament and the transverse process of the L5
      vertebra in young white and black people.
AB  - The anatomy of the iliolumbar ligament (ILL) and the spatial orientation of the
      transverse process of the L5 vertebra were studied in 62 young black (n = 29) and
      white (n = 33) men and women during routine autopsy. The aim of the study was to
      determine possible racial differences in the structure and attachments of the
      iliolumbar ligament. The present study also investigated the spatial orientation
      of the transverse process of the L5 vertebra since the ILL has been reported to
      attach to the transverse process. The measurements of the iliolumbar ligament
      were carried out with a digital vernier caliper while the transverse process
      angles were measured with an adjustable protractor. The ligament in black people
      was made up of a single, markedly longer band compared to white people, where the
      ligament was made up of two shorter bands. The ILL measured 61.8 +/- 1.3 mm in
      black and 33.2 +/- 1.5 mm white men, and in black women 61.3 +/- 0.9 mm versus
      32.2 +/- 1.2 mm in white women (p <0.01). Further, the ILL was markedly wider in
      black than white subjects (p <0.01). The horizontal and vertical angle also
      varied greatly between black and white subjects (p <0.01). These are previously
      unrecognized observations. Albeit unsubstantiated, these findings may have
      implications for understanding the etiology of various low back stress problems.

PMID- 10072571
TI  - A new manual power grip.
AB  - A manual power grip for holding a cylindrical object using a relaxed index finger
      is described and analysed. In a group of 21 young adult students it provided
      greater grip strength than the conventional oblique power grip. It allowed a
      significant increase in the range of adduction-abduction at the wrist. In recent
      years it appears to have been empirically used by a number of top class racquet
      players and is the basis of the modern assault rifle grip. A new design of strain
      gauge dynamometer, in the shape of a cylinder, which permits the testing of a
      number of grip types and wrist positions is described. Standard grip testing
      protocol is used with this device which also allows the concomitant use of a
      goniometer for the assessment of wrist mobility.

PMID- 10072572
TI  - A rare insertion site for abductor pollicis longus and extensor pollicis brevis
      muscles.
AB  - During an investigation performed on cadaver forearms in the anatomy department,
      an unusual insertion of the abductor pollicis longus (APL) muscle together with
      the extensor pollicis brevis (EPB) muscle was encountered unilaterally in a 40
      year-old male cadaver forearm. APL originated from the posterior ulnar surface
      distal to the anconeus, the adjoining interosseous membrane and middle third of
      the posterior radial surface. It lay distal to the supinator muscle and close to
      the EPB, while the EPB arose from the posterior radial surface and from the
      adjacent interosseous membrane. These muscles were inserted to the palmar side of
      the base of the first metacarpal bone together. To our knowledge, this variation
      has not been cited in recent medical literature.

PMID- 10072573
TI  - Report of the fourth international workshop on human chromosome 1 mapping 1998 

PMID- 10072574
TI  - Analysis of the monomeric alphoid sequences in the pericentromeric region of
      human chromosome 7.
AB  - To further define the structure of the pericentromeric region of human chromosome
      7, we have identified and characterized a YAC clone (YAC 311.H5) containing the
      D7S1480 locus, which maps to the short arm near the centromere of this
      chromosome, by linkage in CEPH families and radiation hybrid analysis. This YAC
      contains two new blocks of alphoid DNA (named Z5 and Z6). Both Z5 and Z6 show
      monomeric structures and a lack of higher-order repeats, and, therefore, belong
      to suprachromosomal family type 4 (M1). The orientation of the two blocks and the
      physical distances over the region were defined by pulsed-field gel
      electrophoresis (PFGE) and fluorescence in situ hybridization on chromatin fibers
      (FiberFISH). A YAC contig spanning the centromeric region has been developed by
      STS content.

PMID- 10072575
TI  - Comparative genomics: tracking chromosome evolution in the family ursidae using
      reciprocal chromosome painting.
AB  - The Ursidae family includes eight species, the karyotype of which diverges
      somewhat, in both chromosome number and morphology, from that of other families
      in the order Carnivora. The combination of consensus molecular phylogeny and high
      resolution trypsin G-banded karyotype analysis has suggested that ancestral
      chromosomal fissions and at least two fusion events are associated with the
      development of the different ursid species. Here, we revisit this hypothesis by
      hybridizing reciprocal chromosome painting probes derived from the giant panda
      (Ailuropoda melanoleuca), domestic cat (Felis catus), and man (Homo sapiens) to
      representative bear species karyotypes. Comparative analysis of the different
      chromosome segment homologies allowed reconstruction of the genomic composition
      of a putative ancestral bear karyotype based upon the recognition of 39
      chromosome segments defined by painting as the smallest conserved evolutionary
      unit segments (pSCEUS) among these species. The different pSCEUS combinations
      occurring among modern bear species support and extend the postulated sequence of
      chromosomal rearrangements and provide a framework to propose patterns of genome
      reorganization among carnivores and other mammal radiations.

PMID- 10072576
TI  - Meiotic products of two reciprocal translocations studied by multicolor
      fluorescence in situ hybridization.
AB  - The sperm products of two male carriers of reciprocal translocations were studied
      by fluorescence in situ hybridization (FISH) using a combination of three probes
      for each translocation. One patient carried a t(2;18)(p21;q11.2), the other a
      t(8;9)(q24.2;q32). The probes selected included a centromeric marker for each
      chromosome involved in the translocation plus a third probe distal to the
      translocation breakpoint of one of the translocation chromosomes. This assay
      identifies alternate, adjacent 1, adjacent 2, and 3:1 types of meiotic products.
      It allows the identification of recombination events and also estimation of the
      frequency of diploidy. For the t(2;18), the frequency of normal and balanced
      sperm and of adjacent 1, adjacent 2, and 3:1 products was 43.6%, 29. 8%, 10.5%,
      and 12.8%, respectively. Similar segregation patterns had been reported for this
      donor by direct sperm karyotyping of sperm cells. For the t(8;9), the frequency
      of normal and balanced sperm and of adjacent 1, adjacent 2, and 3:1 products was
      44.4%, 41%, 3.1%, and 9.4%, respectively. The frequency of complementary adjacent
      1 products was statistically different in both the t(2;18) (P < 0. 0001) and the
      t(8;9) (P < 0.0001) carrier. When the number of adjacent 2 products with one
      translocation chromosome (regardless of normal or derivative) was compared to the
      number of adjacent 2 products with the second translocation chromosome (again,
      regardless of normal or derivative), no statistical difference was noted for
      either the t(2;18) (P = 0.32) or the t(8;9) (P = 0.69). Recombination events
      within the interstitial segment of chromosome 2 were statistically higher than
      those seen in chromosome 18 (P < 0. 0001), whereas in chromosomes 8 and 9,
      recombination in the interstitial segments was similar (P = 0.64). The rate of
      diploidy was similar in both the t(2;18) (0.5%) and the t(8;9) (0.6%). Thus, FISH
      provides chromosome information on the sperm products produced by translocation
      carriers, although it cannot provide an assessment of the full chromosome
      complement of the spermatozoon.

PMID- 10072577
TI  - Meiotic drive favors Robertsonian metacentric chromosomes in the common shrew
      (Sorex araneus, Insectivora, mammalia).
AB  - Meiotic drive has attracted much interest because it concerns the robustness of
      Mendelian segregation and its genetic and evolutionary stability. We studied
      chromosomal meiotic drive in the common shrew (Sorex araneus, Insectivora,
      Mammalia), which exhibits one of the most remarkable chromosomal polymorphisms
      within mammalian species. The open question of the evolutionary success of
      metacentric chromosomes (Robertsonian fusions) versus acrocentrics in the common
      shrew prompted us to test whether a segregation distortion in favor of
      metacentrics is present in female and/or male meiosis. Performing crosses under
      controlled laboratory conditions with animals from natural populations, we found
      a clear trend toward a segregation distortion in favor of metacentrics during
      male meiosis, two chromosome combinations (gm and jl) being significantly
      preferred over their acrocentric homologs. Apart for one Robertsonian fusion
      (hi), this trend was absent in female meiosis. We propose a model based on
      recombination events between twin acrocentrics to explain the difference in
      transmission ratios of the same metacentric in different sexes and unequal drive
      of particular metacentrics in the same sex. Pooled data for female and male
      meiosis revealed a trend toward stronger segregation distortion for larger
      metacentrics. This is partially in agreement with the frequency of metacentrics
      occurring in natural populations of a chromosome race showing a high degree of
      chromosomal polymorphism.

PMID- 10072578
TI  - Assignment of the human endogenous retrovirus S71 (SSAV1) to chromosome 18 band
      q12.3 by radiation hybrid mapping.

PMID- 10072579
TI  - Development of arm-specific and subtelomeric region-specific painting probes for
      Chinese hamster chromosomes and their utility in chromosome identification of
      Chinese hamster cell lines.
AB  - Arm-specific and subtelomeric region-specific painting probes for Chinese hamster
      chromosomes have been generated by microdissection and use of the degenerate
      oligonucleotide-primed polymerase chain reaction (DOP-PCR). Fluorescence in situ
      hybridization (FISH) analyses using these probes demonstrated their specificity.
      These probes painted every chromosome arm and a total of 15 subtelomeric regions,
      namely, both ends of chromosomes 1, 2, 3, 4, and 8 and one end of chromosome arms
      5q, 6q, 7q, 9p, and Xp. Many cryptic chromosomal rearrangements in the CHO-9 and
      V79 cell lines that were not detectable with whole chromosome paints could be
      recognized when these newly developed probes were used.

PMID- 10072580
TI  - Molecular cloning, expression, and chromosomal localization of a ubiquitously
      expressed human 6-phosphofructo-2-kinase/ fructose-2, 6-bisphosphatase gene
      (PFKFB3).
AB  - We report the identification of a human 6-phosphofructo-2-kinase/fructose 2,6
      bisphosphatase gene (PFKFB3) isolated from a human fetal brain cDNA library. The
      gene was localized to 10p15-->p14 by fluorescence in situ hybridization. The
      entire cDNA (4,322 bp) codes for a polypeptide of 520 amino acid residues
      (molecular weight, 59.571 kDa). Structural analysis showed the presence of a
      kinase domain located at the amino terminus and a bisphosphatase domain at the
      carboxy terminus, characteristic of previously described 6-phosphofructo-2
      kinase/fructose 2, 6-bisphosphatase isozymes. In addition, a phosphorylation site
      for cAMP-dependent protein kinase was found at the carboxy terminus. Northern
      blot analysis showed the presence of a unique 4.8-kb mRNA expressed in the
      different tissues studied. In mammalian COS-1 cells, this cDNA drives the
      expression of an active isozyme. Taken together, these results identify the
      presence of a gene coding for a human 6-phosphofructo-2-kinase/fructose 2,6
      bisphosphatase isozyme which is ubiquitously expressed.

PMID- 10072581
TI  - Genomic structure, sequence, and refined mapping of the human intersectin gene
      (ITSN), which encompasses 250 kb on chromosome 21q22.1-->q22.2.
AB  - The ubiquitously expressed and brain-specific human intersectin (ITSN) isoforms
      are scaffold proteins probably involved in general endocytosis and synaptic
      vesicle recycling, respectively. Here, analysis of 21q22.1-->q22.2 genomic
      sequence revealed that ITSN consists of 41 exons spanning approximately 250 kb
      and maps between GART and D21S325. The probable function of the ITSN isoforms and
      mapping position of ITSN suggest that disproportionate expression of this gene
      may be implicated in the phenotypic characteristics of Down syndrome.

PMID- 10072582
TI  - Human outer dense fiber gene, ODF2, localizes to chromosome 9q34.
AB  - We have isolated the human homolog of the rat Odf2 gene. In rat, Odf2, the 84-kDa
      major outer dense fiber protein, interacts strongly and specifically with Odf1,
      the 27-kDa major outer dense fiber protein. The interaction is mediated by
      leucine zippers during ODF assembly along the sperm axoneme. We compared homology
      and genomic structure to rat and mouse Odf2 genes. Using fluorescence in situ
      hybridization, we mapped the human Odf2 gene (ODF2) to chromosome 9q34.

PMID- 10072583
TI  - Assignment of the human skeletal muscle [FC12]a-actin gene (ACTA1) to chromosome
      1q42.13-->q42.2 by radiation hybrid mapping.

PMID- 10072584
TI  - Assignment of the human genes coding for cytochrome c oxidase subunits Va
      (COX5A), VIc (COX6C) and VIIc (COX7C) to chromosome bands 15q25, 8q22-->q23 and
      5q14 and of three pseudogenes (COX5AP1, COX6CP1, COX7CP1) to 14q22, 16p12 and
      13q14-->q21 by FISH and radiation hybrid mapping.

PMID- 10072585
TI  - Reassignment of peptidyl prolyl isomerase-like 1 gene (PPIL1) to human chromosome
      region 6p21.1 by radiation hybrid mapping and fluorescence in situ hybridization.

PMID- 10072586
TI  - Assignment of the GOV (Glioblastoma overexpressed) gene to human chromosome band
      19p13.2 by fluorescence in situ hybridization.

PMID- 10072587
TI  - Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor.
AB  - The ING1 gene encodes p33(ING1), a putative tumor suppressor for neuroblastomas
      and breast cancers, which has been shown to cooperate with p53 in controlling
      cell proliferation. We have isolated a novel human gene, ING1L, that potentially
      encodes a PHD-type zinc-finger protein highly homologous to p33(ING1).
      Fluorescence in situ hybridization and radiation-hybrid analyses assigned ING1L
      to human chromosome 4. Both ING1 and ING1L are expressed in a variety of human
      tissues, but we found ING1L expression to be significantly more pronounced in
      tumors from several colon-cancer patients than in normal colon tissues excised at
      the same surgical sites. Although the significance of this observation with
      respect to carcinogenesis remains to be established, the data suggest that ING1L
      might be involved in colon cancers through interference with signal(s)
      transmitted through p53 and p33(ING1).

PMID- 10072588
TI  - Assignment of persephin (PSPN), a human neurotrophic factor, to chromosome
      19p13.3 by radiation hybrid mapping and somatic cell hybrid PCR.

PMID- 10072589
TI  - Assignment of the human dicarboxylate carrier gene (DIC) to chromosome 17 band
      17q25.3.

PMID- 10072590
TI  - Assignment of the cellular retinol-binding protein 2 gene (RBP2) to human
      chromosome band 3q23 by in situ hybridization.

PMID- 10072591
TI  - Assignment of the cyclin I gene (Ccni) to mouse chromosome 5E3.3-F1. 3 by in situ
      hybridization.

PMID- 10072592
TI  - Assignment of the porcine ryanodine receptor 3 gene (RYR3) to chromosome 7q22-
      >q23.

PMID- 10072593
TI  - Assignment of the human ADP-ribosylation factor-like 3 (ARL3) gene to chromosome
      10 band q23.3 by radiation hybrid mapping.

PMID- 10072594
TI  - Assignment of UBE2D1 to human chromosome bands 10q11.2-->q21 by in situ
      hybridization.

PMID- 10072595
TI  - Assignment of the human mitochondrial tryptophanyl-tRNA synthetase (WARS2) to
      1p13.3-->p13.1 by radiation hybrid mapping.

PMID- 10072597
TI  - Assignment of the oxoglutarate carrier gene (SLC20A4) to human chromosome
      17p13.3.

PMID- 10072596
TI  - Molecular cloning, mapping, and characterization of two novel human genes, ORCTL3
      and ORCTL4, bearing homology to organic-cation transporters.
AB  - Through a large-scale sequencing of genomic DNA at 3p22-->p21.3, we have isolated
      two human genes (ORCTL3 alias OCTL1 and ORCTL4 alias OCTL2) encoding novel
      members of the family of organic-cation transporter molecules. The predicted
      proteins revealed the highest similarities to recently- isolated organic-cation
      transporter proteins, rat OCT-1r, rat NLT and mouse NKT. The transcripts of both
      genes were expressed ubiquitously in various human tissues, but some tissue
      specific transcripts were also observed in kidney, testis, or skeletal muscle.
      The two genes are clustered within a 52-kb region of genomic DNA and ORCTL4 lies
      about 27 kb telomeric to ORCTL3 in the genomic DNA sequence in a tail-to-head
      orientation.

PMID- 10072598
TI  - Assignment of big MAP kinase (PRKM7) to human chromosome 17 band p11.2 with
      somatic cell hybrids.

PMID- 10072599
TI  - Assignment of Gldc encoding glycine decarboxylase to mouse chromosome 19C by in
      situ hybridization and a CA repeat polymorphism in the Gldc gene.

PMID- 10072600
TI  - Conservation of pericentromeric duplications of a 200-kb part of the human
      21q22.1 region in primates.
AB  - We analyzed the conservation of large paralogous regions (more than 200 kb) on
      human chromosome regions 21q22.1 and 21q11.2 and on pericentromeric regions of
      chromosomes 2, 13, and 18 in three nonhuman primate species. Orthologous regions
      were found by FISH analysis of metaphase chromosomes from Gorilla gorilla, Pan
      troglodytes, and Pongo pygmaeus. Only one orthologous region was detected in
      chromosomes of P. pygmaeus, showing that the original locus was at 21q22.1 and
      that the duplication arose after the separation of Asian orangutans from the
      other hominoids. Surprisingly, the paralogous regions were more highly conserved
      in gorilla than in chimpanzee. PCR amplification of STSs derived from sequences
      of the chromosome 21 loci and low-stringency FISH analysis showed that this
      duplication occurred recently in the evolution of the genome. Different rates of
      sequence evolution through substitutions or deletions, after the duplication, may
      have resulted in diversity between closely related primates.

PMID- 10072601
TI  - Centrosome amplification as a possible mechanism for numerical chromosome
      aberrations in cerebral primitive neuroectodermal tumors with TP53 mutations.
AB  - Although alterations in chromosome number have frequently been detected in human
      tumor cells and associated with tumor initiation and progression, the causal
      mechanisms are still not understood. One protein known to be involved in
      maintaining genetic stability is tumor suppressor p53. In mice, p53 has been
      implicated in the maintenance of diploidy (Cross et al., 1995) and the regulation
      of centrosome duplication (Fukasawa et al., 1996). Here we report on cerebral
      primitive neuroectodermal tumors that lacked the wild-type p53 gene (TP53) and
      showed multiple numerical chromosome aberrations, as detected by comparative
      genomic hybridization. In these tumors, the centrosome number was significantly
      higher than in a control tumor without a detected TP53 mutation and with few
      chromosomal imbalances. These findings indicate that abnormal centrosome
      amplification can occur in human tumors lacking wild-type TP53 and may be a
      mechanism by which numerical chromosome aberrations are generated.

PMID- 10072602
TI  - Organization and expression of rat Tspy.
AB  - We have isolated both a full-length rat Tspy cDNA from testicular mRNA by rapid
      amplification of cDNA ends (RACE) and RT-PCR and a full-length rat Tspy gene from
      genomic DNA by PCR. In contrast to the mouse, where Tspy is present in a single
      copy and is apparently functionless, and to man and cattle, where TSPY is
      organized in a moderately repetitive cluster, the rat Tspy locus apparently
      consists of one complete functional and one truncated, probably nonfunctional,
      copy, coherently localized on Yp, as revealed by FISH analysis.

PMID- 10072603
TI  - FISH on sperm heads allows the analysis of chromosome segregation and
      interchromosomal effects in carriers of structural rearrangements: results in a
      translocation carrier, t(5;8)(q33;q13).
AB  - Using three-color fluorescence in situ hybridization (FISH) with specific DNA
      probes, we have determined the chromosome segregation pattern of the translocated
      chromosomes in a human male carrier of a reciprocal translocation,
      t(5;8)(q33;q13). At the same time, we have assessed the possible interchromosomal
      effect on pair 21 using dual-color FISH. The segregation results showed that a
      45.12% of the spermatozoa analyzed resulted from alternate segregation, 38.31%
      resulted from adjacent I, 6.97% from adjacent II, and 6.56% from 3:1 segregation.
      Finally, 1.23% could be either diploid sperm or 4:0 segregation. In both types of
      adjacent segregations, an excess of products containing short translocated
      segments (adjacent I) and interstitial regions (adjacent II) were found. Products
      resulting from the presence of an interstitial chiasma in pair 5 (1.26%), were
      found much more frequently (P < 0.0001) than those resulting from an interstitial
      chiasma in pair 8 (0.13%) (evaluated after adjacent II segregation). In 3:1
      segregation, the products containing one chromosome were observed more frequently
      than those containing three chromosomes (P < 0.0001). No evidence of an
      interchromosomal effect on chromosome 21 was detected, the percentage of disomy
      21 being similar to that in the controls (0.23% vs. 0.37%). However, the
      percentage of diploid sperm (1.18%) was significantly higher (P < 0. 0001) than
      that in the controls (0.27%). FISH therefore appears to be a useful technique for
      assessing the percentage of abnormal sperm in translocation carriers. Their
      application in assisted reproduction centers could offer patients more accurate
      genetic counseling.

PMID- 10072604
TI  - Two extended arrays of a satellite DNA sequence at the centromere and at the
      short-arm telomere of Chinese hamster chromosome 5.
AB  - We have cloned a Chinese hamster chromosome-specific repeated sequence (SatCH5).
      This satellite is composed of a 33-bp unit organized in two extended tandem
      arrays. It is localized at the centromere and at the short-arm subtelomere of
      chromosome 5. Altogether, SatCH5 covers about 1-2 Mb per diploid genome and is
      not present in other species, including the Syrian hamster and mouse. Since it is
      known in the Chinese hamster and numerous other vertebrate species that telomeric
      (TTAGGG)n repeats are localized at the centromeres of several chromosomes, we
      studied the localization of SatCH5 relative to (TTAGGG)n sequences. Using two
      color fluorescence in situ hybridization on stretched chromosomes and on DNA
      fibers, we have shown that at the centromere of chromosome 5 SatCH5 and the
      (TTAGGG)n arrays are contiguous. SatCH5 is the first chromosome-specific
      repetitive sequence located at both the pericentromeric and subtelomeric regions
      of the same chromosome.

PMID- 10072605
TI  - Optimization of the kinetics of cooling of kidneys: a pig model.
AB  - We determined the kinetics of cooling in multiple organ procurement for the
      kidney in a pig model. A biometric analysis by regression enables us to define
      the factors which influence the rate of temperature decrease: weight of the
      donor, average rate of perfusion and difference of temperature between the rectal
      temperature and the temperature of the perfusion solution at initiation of
      cooling. The description of the temperature as a function of time follows an
      exponential model of the type T(t) = T0. e(dt) where d is the rate of decrease.
      The rate of decrease varies according to the above factors. The cellular
      viability ratio (CVR), was correlated to the rate of cooling. The mean CVR was
      91% (SD 4.95) when the rate of cooling was more than 1 degrees C/min. This was
      compared to 75% (SD 11.17) when the rate was less than 1 degrees C/min (p =
      0.023). Our experience leads us to believe that the average cooling rate is
      frequently too low (<1 degrees C/min). This model can be used to predict and
      control the kinetics of cooling and may help to define the best way of cooling
      for future xenotransplantation.

PMID- 10072606
TI  - Central hemodynamic changes in experimental muscle crush injury in pigs.
AB  - To investigate central and pulmonary hemodynamics in a standardized normovolemic
      experimental muscle injury model, 8 anesthetized and mechanically ventilated test
      pigs were intracavally infused with 100 ml of autologous muscle extract over a
      period of 100 min; 8 control pigs received Ringer's solution. The cardiac index
      decreased 20% and the heart rate decreased 10% within 30 min of starting the
      infusion in the muscle extract group and remained depressed. Mean arterial
      pressure increased significantly in both groups. The pulmonary capillary wedge
      pressure and central venous pressure remained relatively unchanged during the 5
      hour study. A 2-fold increase in mean pulmonary arterial pressure and a nearly 4
      fold increase in the pulmonary vascular resistance index was seen in the muscle
      extract infusion group, which however returned to normal. Arterial hemoglobin
      concentration and systemic vascular resistance index remained fairly stationary
      in both groups. Immediate significant decreases in both arterial oxygen
      saturation and arterial oxygen tension were observed in the muscle extract group,
      however both variables recovered towards the end of the experiment. A slight
      increase in arterial blood pH value was noted during the experiment. In
      conclusion, autologous muscle extract infusion causes decreases in heart rate and
      cardiac index, as well as a significant increase in pulmonary vascular tone and
      systemic hypoxemia, emphasizing the detrimental effects of skeletal muscle injury
      following severe trauma.

PMID- 10072607
TI  - Early hemodynamic changes during uncontrolled intra-abdominal bleeding.
AB  - Central hemodynamics was studied in 32 pigs during the first 10 min after making
      a 5-mm laceration in the infrarenal aorta. Blood flow probes were placed
      proximally and distally to the site of the bleeding and also over the portal vein
      and renal artery. We found that the bleeding, which was indicated by a difference
      in the rate of blood flow between the two aortic probes, stopped spontaneously
      after about 3 min. The short-term changes in blood flow rates closely followed
      simple monoexponential functions with mean half-times of 34 (proximal aorta),
      approximately 10 (lower aorta), 27 (splanchnic) and 21 s (kidney) to reach steady
      state levels amounting to 20, 20, 27 and 8% of the baseline flow rates,
      respectively.

PMID- 10072608
TI  - Endotoxin and cytokine release in strangulation obstruction and in partial
      occlusion of the mesenteric artery in pigs.
AB  - BACKGROUND: The study was performed to determine if endotoxin or the cytokines
      interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) are
      liberated from strangulated or partially ischemic small bowel. METHODS:
      Strangulation obstruction was induced by elevating pressure in a gasket placed
      around a loop of ileum until venous pressure reached 50 mm Hg. Low arterial flow
      in a loop of ileum was produced by arterial clamping reducing blood flow by 70%.
      A proximal bowel loop was used for control. Arterial blood flow was measured by
      transit time flowmetry. Blood samples were collected before and after 30, 90 and
      180 min of strangulation or clamping. Plasma levels of endotoxin and cytokines
      (TNF, IL-1 and IL-6) were measured by limulus amebocyte lysate test and
      bioassays, respectively. RESULTS: Strangulation obstruction caused more extensive
      mucosal damage than arterial clamping. Strangulation was followed by markedly
      increased venous concentration and release of IL-6 in the strangulated loop.
      Partial arterial occlusion did not cause increased release of IL-6. Strangulation
      or partial clamping did not influence the concentration of endotoxin, IL-1 or TNF
      in intestinal venous blood. CONCLUSIONS: Strangulation obstruction causes
      increased release of IL-6 to intestinal venous blood. IL-6 levels did not
      increase after 70% reduction of arterial blood flow. The early IL-6 increase was
      not detected in systemic blood. Strangulation did not cause early changes in
      plasma levels of endotoxin, TNF or IL-1.

PMID- 10072609
TI  - Prolonged function of hepatocytes transplanted into the spleens of Nagase
      analbuminemic rats.
AB  - Hepatocytes isolated from F344 rats were transplanted into the spleens of
      congenic Nagase analbuminemic rats (NARs). The morphology and function of the
      transplanted hepatocytes were investigated after 18 months. The hepatocytes had
      formed nodules that occupied approximately 35% of the area of the splenic
      parenchyma on microscopic examination. Ultrastructural examination demonstrated
      that the organelles of the transplanted cells were indistinguishable from those
      of normal hepatocytes. The serum albumin level in NARs at 18 months after
      intrasplenic transplantation (HCTx) was about 3.6% of that in normal rats. We
      confirmed that the hepatocytes in the spleen produced albumin and increased the
      serum albumin level in NARs with HCTx. The NAR model demonstrates the effect of
      HCTx and prolonged changes in the morphology of the hepatized spleen.

PMID- 10072610
TI  - FK506 with portal decompression exerts beneficial effects following extended
      hepatectomy in dogs.
AB  - The present study was designed to elucidate the effectiveness of portal
      decompression and FK506 (FK) pretreatment in extended hepatectomy in dogs. In the
      first set of experiment the effect of portal decompression was evaluated in two
      groups of dogs which underwent extended hepatectomies (80%) with or without
      (control) a side-to-side portacaval shunt. The presence of the shunt
      significantly (p < 0.05) improved the 7-day survival of the animals (57.1%) when
      compared with those of the control group (28.6%) and eventually the portal
      pressure was significantly lower and mean arterial pressure was significantly
      higher in the shunt group (p < 0. 05). Moreover, the animals with lower portal
      pressure (</=220 mm of saline) had a significantly improved 7-day survival rate
      than those with higher portal pressure (p < 0.001). To evaluate the role of FK
      pretreatment in extended hepatectomy, a more severe model of 90% hepatectomy was
      used in four different groups: portacaval shunt, shunt and FK pretreatment, FK
      pretreatment, and hepatectomy only (control). Although the shunt improved the
      survival rate in the 80% hepatectomy model, neither shunt (8.3%) nor FK
      pretreatment (0%) independently improved the survival of the animals when the
      hepatectomy was extended to 90%. FK pretreatment significantly improved the
      survival (33.3%, p < 0.05) and hepatic functions of the animals only in the
      presence of a shunt. Also hepatic microcirculation measured with a laser Doppler
      flowmeter was significantly better in the remnant liver of all treated groups
      than in the control group (p < 0.01). In conclusion, extended hepatectomy (90%)
      could be performed in otherwise normal liver after FK pretreatment and a side-to
      side portacaval shunt, which improve the regenerative response in a stable
      hemodynamic animal.

PMID- 10072611
TI  - Effect of early postoperative enteral feeding on the healing of colonic
      anastomoses in rats. Comparison of three different enteral diets.
AB  - This experimental study compares the effects of early postoperative
      administration of three enteral diets of different compositions on the healing of
      colonic anastomoses. Sixty Wistar rats were subjected to colonic anastomoses.
      Following surgery, the rats were randomly allocated to four groups of 15 each.
      The rats in control group A received an electrolyte and glucose solution, the
      rats in group B received a complete balanced nutrition, in group C a complete
      balanced nutrition supplemented with fiber and in group D an isocaloric
      specialized elemental nutrition enriched with glutamine. The rats were sacrificed
      on day 7 following operation. Rupture of the anastomosis was higher in rats of
      the control group compared to the other three groups. Adhesion formation was more
      extensive in group A in comparison to the other three groups. The anastomotic
      bursting pressures were statistically significantly higher in groups C and D
      compared to the other two groups (p < 0.05). There was no statistically
      significant difference between group C and D (p > 0.05) while a statistically
      significant difference was noted between group B and group A (p < 0.05).
      Histological examination showed more profound inflammatory reaction in group A
      compared to the other three groups. There was also a statistically significant
      difference between group B and groups C and D while inflammatory reaction was of
      no statistically significant difference between group C and group D. Healing of
      the anastomoses was statistically significantly impaired in group A compared to
      the other three groups. There was no statistically significant difference between
      group C and group D while a statistically significant difference was found
      between group B and groups C and D. In conclusion, early postoperative enteral
      feeding improves healing of experimental colonic anastomoses in rats. This effect
      was more evident when fiber-supplemented diets or diets enriched with glutamine
      were administered.

PMID- 10072612
TI  - Evaluation of distal anastomotic intimal hyperplasia: an experimental comparison
      by arteriography, duplex sonography, angioscopy, and intravascular ultrasound.
AB  - Routine follow-up investigation methods after peripheral arterial bypass surgery,
      such as arteriography and colour duplex sonography, do not always allow correct
      analysis of moderate alterations in the vessel wall, e.g. initial stages of
      distal anastomotic intimal hyperplasia (DAIH). The aim of this study was to
      evaluate the efficiency of angioscopy and intravascular ultrasound compared to
      the named routine methods regarding detection of early DAIH. Eight months after
      bilateral femoropopliteal bypass surgery with venous grafts in 18 sheep, we
      investigated the distal anastomotic sites using the named methods. The findings
      were then correlated to histologic specimens. Intravascular ultrasound presented
      the highest sensitivity followed by angioscopy, with results markedly different
      from the findings arrived at by conventional methods.

PMID- 10072613
TI  - Effects of hexose sugars: glucose, fructose, galactose and mannose on wound
      healing in the rat.
AB  - The effects of four hexose sugars (D-glucose, D-fructose, D-galactose, D-mannose)
      on the developing granulation tissue in rats were examined. Cylindrical hollow
      sponge implants were used as an inductive matrix for the growth of granulation
      tissue. In the test group, the implants were injected with 0.1 ml of solution
      containing the different hexoses in 0.01, 0.1 and 1 M concentrations daily for 7
      days while the implants of the control groups were injected with 0.1 ml of
      phosphate-buffered saline solution only. Analyses of granulation tissue and wound
      fluid in the sponge implants were carried out 7 days after implantation. The
      results demonstrated that galactose caused a significant increase in the
      accumulation of granulation tissue as estimated by histological analyses, but no
      significant differences were observed in various chemical analyses. In striking
      contrast, statistically significant decreases were observed in the number of
      leukocytes in wound fluid, in the amount of DNA, RNA, collagen hydroxyproline,
      nitrogen, hexosamines and uronic acids in sponges treated with 0.1 or 1 M
      mannose, reflecting decreased granulation tissue formation. This effect was also
      observed in histological analyses of the specimens. There were no major changes
      in sponges treated with glucose or fructose. In summary, the findings of the
      present study demonstrate that galactose may enhance wound healing and mannose
      treatment inhibits the inflammatory reaction in wound healing and decreases
      granulation tissue formation in an experimental wound model.

PMID- 10072614
TI  - Portal blood flow and liver regeneration in auxiliary partial orthotopic liver
      transplantation in a canine model.
AB  - Functional competition has been shown to lead to a detrimental outcome in
      auxiliary liver transplantation. We evaluated the interaction in auxiliary
      partial orthotopic liver transplantation between the native liver and the graft
      in terms of portal flow and regeneration. The need for diversion of the portal
      flow to the graft was also assessed. Reduced-size liver grafts were transplanted
      orthotopically after partial hepatectomy in beagles. There were two groups: the
      preserved group, where portal inflow to the native liver was preserved, and the
      ligated group, where it was interrupted. Portal flow was measured serially and
      liver regeneration was evaluated on postoperative day 5. Functional competition
      was not observed in the preserved group. On the other hand, ligation of the
      native liver portal vein had no obviously detrimental effects on the remnant
      native liver. This leads to the conclusion that the portal vein to the native
      liver can be safely ligated to prevent functional competition.

PMID- 10072616
TI  - Primary carcinoma in situ of the urinary bladder: diagnosis and management 

PMID- 10072615
TI  - Modified technique of isolated left lung perfusion in the rat.
AB  - Isolated lung perfusion is a novel therapy for the treatment of pulmonary
      metastases to increase current low survival rates. Due to tumor heterogeneity,
      perfusion has to be evaluated in different rat species for efficacy and ideal
      drug regimens. The revised technique of isolated left lung perfusion as described
      by Wang and originally performed in the Fisher rat resulted in a high morbiditity
      in the Wag/Rij rat in our laboratory. Therefore, we modified techniques for
      intubation and anesthesia, and developed a new approach of catheterization with
      improved results.

PMID- 10072617
TI  - Prostate and sexuality: An overview.
AB  - OBJECTIVE: Diseases of the prostate, prostatitis, prostatodynia, benign prostatic
      hyperplasia (BPH), and carcinoma of the prostate interfere with sexual function.
      Since the American Urological Association have issued their position statement in
      1990 that male sexual dysfunction is a recognized disease entity, studies
      examined the interrelation between sexuality and the prostate. These studies were
      identified in our review. METHOD: A computer- and hand-based search of the
      literature was conducted with the key words health-related quality of life,
      sexual function and the various disease states of the prostate, the drawback
      being that validated quality-of-life instruments have just recently and mostly
      nationally been validated. RESULTS: Sexual function is a dimension of quality-of
      life questionnaires with 1 up to 11 questions addressing sexuality. The effect of
      aging on male sexuality as determined in Sweden serves as an important background
      information. Whereas prostadynia and sexual dysfunction aggravate each other, BPH
      and its treatment influence only certain sexual functions. Carcinoma of the
      prostate, untreated or under observation, has the greatest impact on sexuality
      which is tolerated differently from country to country and depends upon the
      expectation of survival. CONCLUSION: The impact of treatment of prostatic
      diseases on sexuality can now be studied easier in utilizing validated
      questionnaires. This update may serve as a base for these upcoming studies.

PMID- 10072619
TI  - Transcutaneous sacral neurostimulation for irritative voiding dysfunction.
AB  - OBJECTIVE: Patients with irritative voiding dysfunction are often unresponsive to
      standard clinical treatment. We evaluated the response of such individuals to
      transcutaneous electrical stimulation of the third sacral nerve. METHODS: 32
      patients with refractory irritative voiding dysfunction (31 female and 1 male;
      mean age 47 years) were recruited to the study. Ambulatory transcutaneous
      electrical neurostimulation was applied bilaterally to the third sacral
      dermatomes for 1 week. Symptoms of frequency, nocturia, urgency, and bladder pain
      were scored by each patient throughout and up to 6 months following treatment.
      RESULTS: The mean daytime frequency was reduced from 11.3 to 7.96 (p = 0.01).
      Nocturia episodes were reduced from a mean of 2.6 to 1.8 (p = 0.01). Urgency and
      bladder pain mean symptom scores were reduced from 5.97 to 4.89 and from 1.48 to
      0.64, respectively. After stopping therapy, symptoms returned to pretreatment
      levels within 2 weeks in 40% of the patients and within 6 months in 100%. Three
      patients who continued with neurostimulation remained satisfied with this
      treatment modality at 6 months. CONCLUSIONS: Transcutaneous third sacral nerve
      stimulation may be an effective and noninvasive ambulatory technique for the
      treatment of patients with refractory irritative voiding dysfunction. Following
      an initial response, patients may successfully apply this treatment themselves to
      ensure long-term relief.

PMID- 10072618
TI  - A new parameter in decision making for transurethral electroresection of benign
      prostate hyperplasia.
AB  - OBJECTIVE: In this study, the clinical usefulness of transition zone (TZ) volume
      (TZV) measured by transrectal ultrasonography (TRUS) was investigated as a new
      parameter for the preoperative prediction of the treatment efficacy of
      transurethral resection of the prostate (TURP). METHODS: Fifty-six men with
      symptomatic benign prostatic hyperplasia (BPH; age 68.6 +/- 9.7 years) underwent
      TURP and were evaluated based on ordinary BPH parameters such as the
      international prostatic symptom score (I-PSS), quality of life (QOL) score, peak
      urine flow and entire prostate volume (PV), as well as the new TZV parameters and
      calculation of the TZ index. Relative risks were adjusted simultaneously for
      potentially confounding variables by multiple logistic regression analysis after
      adjustment for age, QOL, I-PSS, Qmax and residual urine. RESULTS: The adjusted
      relative risk for TURP at a TZ index of 0.1 increased to 4.5 (95% confidence
      interval 2.3-8.78). In general, poor responses were observed in patients with
      less symptomatic scores or lower values prior to operation, but there was a weak
      correlation between treatment outcome and preoperative scores or values of
      ordinary parameters. The volume parameters of BPH and PV did not predict
      treatment efficacy preoperatively, but TZV and the TZ index correlated with the
      treatment efficacy of TURP. CONCLUSION: TZV and the TZ index seem to be useful
      new parameters in preoperative decision-making with regard to TURP.

PMID- 10072620
TI  - Metastasectomy in renal cell carcinoma: A multicenter retrospective analysis.
AB  - OBJECTIVE: In 60-70% of patients with renal cell carcinoma (RCC), metastases
      develop in the course of the disease. In the present analysis, the surgical
      management of metastases is described, and survival data are presented. This
      retrospective analysis may help in the management of future cases. Due to the
      retrospective nature of the data, no comparison between surgical and nonsurgical
      management is possible. METHODS: Between 1985 and 1995, 152 resections of RCC
      metastases were performed in 101 patients at four Dutch Hospitals. Thirty-five
      and 6 patients had metastases resected 2 and 3 times, respectively. In most
      patients, the primary tumor was resected (n = 95). Resections were performed for
      metastases at different locations: lung n = 54, bone n = 42, lymph nodes n = 18,
      cerebrum n = 12 and locations in the spinal canal, thyroid, bowel, and testis.
      Skin excisions were excluded from the analysis. Solitary metastases were resected
      in 40 patients. RESULTS: Median survival after the initial metastasectomy was 28
      months. Initial tumor stage, grade, or size were not related to metastasis
      location or survival. The number of initially resected pulmonary metastases was
      of no influence on survival, however, multiple consecutive resections were
      related with longer survival. Patients with solitary metastases (n = 40) did not
      show longer survival after the first metastasectomy compared to no solitary
      lesions. Better survival was found for lung metastases compared to other tumor
      locations (p = 0.0006, log rank test) and for patients that were clinically tumor
      free after metastasectomy (p = 0.0230, log rank test). Additional immuno- or
      radiotherapy did not independently influence survival. Time interval between
      primary tumor resection and metastasectomy correlated positively with survival: a
      tumor-free interval of more than 2 years between primary tumor and metastasis was
      accompanied by a longer disease-specific survival after metastasectomy. Eleven
      patients were free of disease after metastasectomy with a median time of 47 (14
      65) months. The median time of hospital admittance for metastasectomy was 9 days
      (4-64). Lethal complications were found in 2 patients. Long-term (>5 years)
      disease-free survival was achieved in 7% of patients whereas 14% of patients were
      free of disease with a minimal follow-up of 45 months. CONCLUSIONS: (1) Surgical
      management of metastases could be performed with short hospital stay, and low
      complication rates were found. (2) Disease-free survival was found in 14 and 7%,
      with follow-ups of at least 45 and 60 months, respectively. (3) The longest
      survival was found after surgery for pulmonary lesions. (4) Resection of solitary
      metastases did not result in longer survival compared to resection of nonsolitary
      lesions. (5) An interval shorter than 2 years between primary tumor and
      metastases was correlated with a shorter disease-specific survival.

PMID- 10072621
TI  - Results of immunochemotherapy with interleukin-2, interferon-alpha2 and 5
      fluorouracil in the treatment of metastatic renal cell cancer.
AB  - OBJECTIVE: In patients with advanced metastatic renal cell carcinoma (RCC) seen
      at a single institution, the toxicity and long-term clinical effects of a
      combination therapy with recombinant interleukin-2 (rIL-2), recombinant
      interferon-alpha2 (rIFN-alpha2) and 5-fluorouracil (5-FU) were evaluated. METHOD:
      From August 1992 through August 1997, 47 consecutive patients (38 men) with
      metastatic RCC were treated using rIL-2 and rIFN-alpha2 subcutaneously in
      combination with intravenous 5-FU. An average of 2. 4 cycles/patient (range 1-9)
      was administered. RESULTS: Toxicity grades II and III (World Health Organization)
      were observed in 24 and 17 patients, respectively. We achieved 9 major responses
      (7 complete responses (CR) and 2 partial responses (PR)) for an objective
      response rate of 19.1% (95% confidence interval 9.1-33.3%). A further 13 patients
      (27.7%) had a stabilization of disease. After a mean follow-up of 17.9 (2-53)
      months, 4 patients are alive with no evidence of disease. The 1- and 3-year
      survival probability was 70 and 37%, respectively. In an univariate analysis, two
      prognostic factors were correlated with disease outcome: Karnofsky performance
      index (p = 0.01) and the presence of bone metastases (p = 0.023). CONCLUSION:
      This triple-drug combination therapy was effective in the treatment of
      progressive RCC in almost every fifth patient.

PMID- 10072622
TI  - Results of a clinical care pathway for radical prostatectomy patients in an open
      hospital - multiphysician system.
AB  - OBJECTIVES: The object of this study was to evaluate the results of a
      comprehensive clinical care pathway (CCP) aimed at reducing the length of
      hospitalization and overall cost for patients undergoing radical prostatectomy in
      a setting including both academic and private physicians. METHODS: The clinical
      records of 1,129 consecutive patients who underwent radical prostatectomy by 24
      urologists between July 1, 1990, and December 31, 1996, were reviewed. The
      factors considered were length of stay, morbidity and mortality, readmission
      rates, and average cost. The CCP was implemented on January 1, 1994. Its scope
      was to minimize preoperative evaluation, eliminate the preoperative hospital
      stay, standardize postoperative care and provide intensive patient education.
      RESULTS: The average length of stay decreased significantly after implementation
      of the CCP (8.1 vs. 4.9 days, p = 0.0001). In 1990, there was a large difference
      in length of stay between academic and private physicians (8.3 vs. 12.6 days) (p
      = 0. 02) but by 1 year after implementation of the CCP there was virtually no
      difference (4.69 vs. 4.71 days) (p > 0.05). Complication rates were similar
      before and after implementation of the CCP. Using the average 1993 cost/case as
      the baseline preCCP figure, the average cost of radical prostatectomy decreased
      by 16% in 1994 and by 22% in 1995. CONCLUSIONS: It is possible to successfully
      implement a CCP in a multi-physician system to reduce length of stay and cost of
      radical prostatectomy without subjecting the patient to a greater risk of
      complication.

PMID- 10072623
TI  - Changes of urodynamic findings after radical retropubic prostatectomy.
AB  - OBJECTIVES: We wanted to evaluate the urodynamic changes of radical retropubic
      prostatectomy in patients with localized prostate cancer and identify specific
      factors that could influence the postoperative continence status. METHODS: Sixty
      six consecutive patients (mean age 68 years) were studied urodynamically within 1
      week before surgery, and 44 of them at a mean 7.6 months after radical
      intervention. RESULTS: Complete urinary continence was achieved in 37/44 men (84.
      1%) after 6 months and in 43/44 patients (97.7%) 1 year after surgery. Stress
      incontinence of varying degree improved with time. Seven patients demonstrated a
      moderate incontinence 4 months after radical prostatectomy and 1/7 was still
      incontinent after 1 year. Mean flow rate, maximum detrusor pressure, maximum
      urethral closure pressure (at rest and voluntary contraction of the sphincter)
      and functional urethral length showed significant changes after surgery. Detrusor
      instability, which was present in 31.8% of the 66 patients preoperatively, was
      not responsible for any case of postoperative incontinence. The urethral pressure
      profile was significantly reduced in all patients after surgery. CONCLUSIONS: The
      present study indicates that there are no preoperative alterations in bladder
      function such as detrusor instability to identify patients at risk for
      postoperative incontinence. Postoperative incontinence seems to depend upon
      sphincteric deficiency as expressed by the reduced pressures in the sphincteric
      mechanism.

PMID- 10072624
TI  - Influence of local tumour stage and grade on reliability of serum prostate
      specific antigen in predicting skeletal metastases in patients with
      adenocarcinoma of the prostate.
AB  - OBJECTIVE: To determine whether serum prostate-specific antigen (PSA) can be
      reliably used to predict the absence or presence of skeletal metastases on the
      bone scan in patients with adenocarcinoma of the prostate. METHODS: We studied
      450 consecutive men presenting with adenocarcinoma of the prostate between 1991
      and 1995. Serum PSA was measured by the Hybritech Tandem-R monoclonal
      immunoradiometric assay and bone scanning was performed with 99m-technetium
      labelled methylene diphosphonate. In total, 46 patients were excluded for one or
      more of the following reasons: serum PSA not available; radionuclide bone scan
      inconclusive; histology of the prostate other than adenocarcinoma; hormonal or
      other therapy given prior to obtaining the serum PSA and/or bone scan. RESULTS:
      Of the 404 patients included, 43% had poorly differentiated (grade 3), 74% had
      locally advanced (stages T3-4) tumours and 50% had skeletal metastases. The mean
      and median serum PSA were 348 and 52 ng/ml, respectively, and 77% of the patients
      had a serum PSA >20 ng/ml. The negative predictive value (for the absence of
      metastases on bone scan) of a serum PSA <20 ng/ml was 87% for the whole group of
      patients, 92, 94 and 70% for grade 1, 2 and 3 tumours, and 95, 83 and 50% for
      stage T1-2, T3 and T4 tumours, respectively. The positive predictive value (for
      the presence of metastases on bone scan) of a serum PSA >100 ng/ml was 80% for
      the whole group of patients. CONCLUSIONS: In patients presenting with
      adenocarcinoma of the prostate, serum PSA alone is not sufficiently reliable to
      predict the absence or presence of metastases on the radionuclide bone scan. In
      patients with grade 3 and clinical stage T3-4 tumours, a bone scan should be
      obtained for accurate staging, regardless of the serum PSA value.

PMID- 10072625
TI  - Reliability of the routine cytological diagnosis in bladder cancer.
AB  - OBJECTIVES: To establish the reliability of three cytopathologists for
      cytological diagnosis of primary bladder tumors. METHODS: Preoperative voided
      urine specimens of 71 patients with bladder cancer and 55 noncancer controls were
      retrospectively and blindly reviewed by 3 independent cytologists, and their
      results compared. The estimation of the interobserver agreement was calculated
      using the weighted kappa coefficient. A multivariate analysis was carried out to
      identify the factors associated with the disagreement between the three
      observers. The sensitivity and specificity for each of the participants was
      calculated in order to clearly identify the origin of the disagreement, in terms
      of the performance of the diagnostic test in the hands of each observer. A
      comparison of the overall diagnostic performance was made by plotting sensitivity
      versus 1-specificity. RESULTS: The weighted kappa coefficient among the 3
      observers was 0.46. The multivariate analysis did not identify any variable that
      could have caused such disagreement. Vast differences in sensitivity and
      specificity were detected between observer 1 (sens. 0.90, spec. 0.45) and
      observers 2 (sens. 0.67, spec. 0.72) and 3 (sens. 0.71, spec. 0.80), but the
      overall diagnostic performance (sensitivity vs. 1-specificity) was superimposable
      in the 3 cases (p = NS). CONCLUSIONS: Simple, reproducible and agreed-on
      diagnostic criteria should be established to yield reliable results in a group of
      cytologists. The consideration of individual diagnostic performances can give a
      false idea of homogeneity between observers. In this field, concordance analysis
      makes quality control reliable and should be a routine procedure of any pathology
      department.

PMID- 10072626
TI  - Holmium:YAG laser ureterolithotripsy.
AB  - OBJECTIVE: To report on the experience obtained in the treatment of a series of
      150 cases of ureteral stone disease by means of the holmium:yttrium-aluminum
      garnet (Ho:YAG) laser. METHODS: One hundred and fifty consecutive cases treated
      by means of Ho:YAG laser ureterolithotripsy have been reviewed in order to assess
      the results. In 81 cases the stones were located in the lower third, in 47 in the
      medium third, and in 22 cases in the upper third of the ureter. The laser was set
      at a power of 8-10 W and at a frequency of between 6 and 10 Hz. Thin
      ureteroscopes were selected, such as the 7-Fr Gautier or the new ultrathin 4.8-Fr
      Wolf instrument. In some cases other ureteroscopes were chosen. RESULTS:
      Lasertripsy was effective in every kind of stone, allowing fragmentation into
      portions measuring at most 4 mm (largest diameter) or disintegration. The
      clearance rate of the stones was 92.6% during the 30-day follow-up period.
      Calcium dihydrate stones were of course more easily broken than monohydrate ones.
      No damage to the ureter was observed following the vaporization which is produced
      by this kind of laser, since particular attention was paid to avoid any contact
      between the laser beam and the ureteral mucosa. In some instances ureteroscopic
      maneuvering provoked some slight lacerations. In a few cases accidental contact
      of the laser beam with the ureteral mucosa produced extremely small coagulations
      of no immediate or postoperative relevance. CONCLUSIONS: The Ho:YAG laser
      constitutes an effective instrument for the fragmentation of any kind of ureteral
      stone; it allows the use of thin or ultrathin instruments and, if manipulated
      with care, does not damage the ureteral mucosa or the ureteral wall.

PMID- 10072627
TI  - Urolithiasis and the protease inhibitor indinavir.
AB  - OBJECTIVE: To evaluate specific urological abnormalities in patients treated with
      the protease inhibitor indinavir. METHODS: A series of 155 consecutive human
      immunodeficiency virus-positive patients were treated with indinavir 800 mg p.o.
      three times a day. Of these, 14 (9%) treated for 1-321 (average 110) days
      experienced severe flank pain and were subjected to clinical and laboratory
      examinations. RESULTS: Abdominal X-ray was consistently negative for stones.
      Ultrasonography showed upper-tract dilatation in 12 patients. Intravenous
      urography showed obstruction above a radiolucent obstacle in 7 patients; in 2
      cases, there was a marked delay in urine excretion on the obstructed side. The
      mean urine pH was 6. Urine culture was negative. Serum uric acid, phosphorus, and
      calcium levels were normal. In 8 patients there was slight renal insufficiency,
      and 4 patients required ureteral stenting. In all cases, hyperhydration and oral
      analgesia led to a favorable outcome. In 3 patients, chemical analysis of the
      stone demonstrated monohydrate indinavir crystals. CONCLUSIONS: In our
      experience, indinavir therapy is associated with urolithiasis in 9% of the cases.
      Hydration, analgesia, and acidification of the urine usually lead to a favorable
      clinical outcome. Prophylactic hydration and acidification of the urine are
      extremely important.

PMID- 10072628
TI  - Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in
      renal cell carcinoma.
AB  - OBJECTIVES: This study was designed to examine the immunohistochemical expression
      of bcl-2, p53, and proliferating cell nuclear antigen (PCNA) and the relation of
      this expression to clinicopathological characteristics and prognosis in renal
      cell carcinoma (RCC). METHODS: The expression of bcl-2, p53 protein, and PCNA was
      studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens
      from 53 patients whose clinicopathological data had already become clear.
      RESULTS: The expression of the bcl-2 protein was recognized in 34 cases (64%);
      the expression of the p53 protein, however, was seen in only 1 case. Bcl-2
      positivity was not associated with any pathological parameters or prognosis. If
      the percentage of PCNA-positive cancer cells as compared to the total amount of
      cancer cells was defined as a labeling index (LI), a high PCNA LI number
      correlated significantly with a high T category, high grade, venous invasion, and
      shortened survival. Among the conventional pathological parameters, the T
      category, nuclear grade, and venous invasion had the most significant effect on
      prognosis. A multivariate analysis in the parameters of PCNA, T category, nuclear
      grade, and venous invasion demonstrated that only nuclear grade had a significant
      effect on prognosis. CONCLUSIONS: The inhibitory effect of the bcl-2 gene on
      apoptosis related to tumor development is not clear, and the expression of the
      p53 protein is uncommon in RCC. PCNA seems to be a good objective and
      quantitative marker of the biological malignant potential in RCC, although the
      assessment of malignant potential in combination with conventional pathological
      parameters is indispensable.

PMID- 10072629
TI  - Telomerase activity in malignant and benign renal tumors.
AB  - OBJECTIVES: An important characteristic of malignant cells is their unlimited
      replicative potential, their immortality. In conferring this immortality, the
      enzyme telomerase is believed to play a crucial role. The detection of telomerase
      activity provides new knowledge regarding the biologic growth behavior of tumors
      and offers new diagnostic and therapeutic tools. METHODS: In the present study
      the sensitive TRAP assay (telomeric repeat amplification protocol) was used to
      examine 44 malignant renal tumors and 8 benign tumors of the kidney and 52
      specimens of normal renal tissue for telomerase activity. RESULTS: Telomerase
      activity was detected in 63% of tissue samples obtained from histologically
      confirmed renal cell carcinomas. In cases of renal cell carcinoma restricted to
      the kidney, telomerase activity was detected in 58%. In cases in which tumor
      growth has progressed beyond the limits of the organ, telomerase activity was
      found in 69%. This stage dependence, however, did not reach statistical
      significance. No correlation to tumor grading was observed. Telomerase activity
      was found less frequent in chromophobe renal cell carcinomas. Neither the 8
      benign renal tumors (4 oncocytomas and 4 angiomyolipomas) nor the specimens of
      normal kidney showed any evidence of telomerase activity. CONCLUSIONS: The
      proportion of remarkable slow-growing renal cell carcinomas showing telomerase
      activity is less than in other malignancies and may correlate with biologic
      growth behavior. Possible explanations include the presence of an alternative
      pathway, called ALT (alternative lengthening of telomeres) and an association
      with the loss or presence of the telomerase suppressor on the short arm of
      chromosome 3. Prolonged follow-up will be of special interest to determine
      whether lack of telomerase activity predicts favorable outcome.

PMID- 10072630
TI  - A history of complement genetics.
AB  - After a brief review of the history of the complement system from the original
      observations in the 1880s, the history of complement genetics is outlined,
      beginning in 1919 with the recognition of the complement-deficient guinea pig. A
      highly personal view is then presented of the early days of the discovery of
      human complement structural gene polymorphisms and deficiencies, particularly
      those of C3, BF and factor I. Finally, some recent work based on features in the
      DNA of the MHC-encoded complement genes is outlined that sheds some light on
      their evolution.

PMID- 10072631
TI  - Molecular genetics of the human MHC complement gene cluster.
AB  - The human major histocompatibility complex (MHC) complement gene cluster (MCGC)
      is a highly variable region that is characterized by polymorphisms, variations in
      gene size and gene number, and associations with diseases. Deficiencies in
      complement C2 are either due to abolition of C2 protein synthesis by mini
      deletions that caused frameshift mutations, or blocked secretion of the C2
      protein by single amino acid substitutions. One, two or three C4 genes may be
      present in a human MCGC haplotype and these genes may code for C4A, C4B, or both.
      Deficiencies of C4A or C4B proteins are attributed to the expression of identical
      C4 isotypes or allotypes from the C4 loci, the absence or deletion of a C4 gene,
      2-bp insertion at exon 29 or 1-bp deletion at exon 20 that caused frameshift
      mutations. The C4 genes are either 21 or 14.6 kb in size due to the presence of
      endogenous retrovirus HERV-K(C4) in the intron 9 of long C4 genes. A deletion or
      duplication of a C4 gene is always accompanied by its neighboring genes, RP at
      the 5' region, and CYP21 and TNX at the 3' region. These four genes form a
      genetic unit termed the RCCX module. In an RCCX bimodular structure, the
      pseudogene CYP21A, and partially duplicated gene segments TNXA and RP2 are
      present between the two C4 loci. The RCCX modular variations in gene number and
      gene size contributed to unequal crossovers and exchanges of polymorphic
      sequences/mutations, resulting in the homogenization of C4 polymorphisms and
      acquisitions of deleterious mutations in RP1, C4A, C4B, CYP21B and TNXB genes.
      RD, SKI2W, DOM3Z and RP1 are the four novel genes found between Bf and C4. RD and
      Ski2w proteins may be related to RNA splicing, RNA turnover and regulation of
      translation. The functions of Dom3z and RP1 are being investigated. The complete
      genomic DNA sequence between C2 and TNX is now available. This should facilitate
      a complete documentation of polymorphisms, mutations and disease associations for
      the MCGC.

PMID- 10072632
TI  - C1q knock-out mice for the study of complement deficiency in autoimmune disease.
AB  - In humans, homozygous deficiency of the first component of the classical pathway
      of complement, C1q, is a powerful disease susceptibility factor for the
      development of systemic lupus erythematosus (SLE). This strong association
      indicates that a functional activity of C1q protects from the development of SLE.
      Studies in vitro have shown that C1q can bind apoptotic keratinocytes suggesting
      that it may have an important role in the clearance of apoptotic cells. C1q
      deficient mice, generated by gene targeting, showed an increased mortality and
      25% of the mice had histological evidence of glomerulonephritis characterised by
      multiple apoptotic cell bodies and immune deposits, assessed by
      immunofluorescence and electron microscopy. These observations are compatible
      with the hypothesis that C1q deficiency causes autoimmunity by an impaired
      clearance of apoptotic cells.

PMID- 10072633
TI  - Evolution of the terminal complement genes: ancient and modern.
AB  - The data on the structure and relationships of the TCC genes are reviewed and a
      model is presented for the processes of gene duplication by which the modern
      genes might have evolved. Data on variations of the overall gene numbers and
      relationships in modern species are also reviewed, together with the
      polymorphisms found in man. The apparent contradictions of lack of allelic
      association between markers and lack of direct evidence for recombination in the
      C6/C7 gene region is also discussed.

PMID- 10072634
TI  - Terminal complement component deficiencies in Japan.
AB  - From the serological screening for complement component deficiencies, we found 2
      subjects with inherited C5 deficiency (C5D), 4 with C6D, 6 with C7D, 4 with C81
      (alpha-gamma subunit) D and 138 with C9D among 145,640 healthy Japanese blood
      donors. Recently, the genetic bases of some of the C6D, C7D, C81D and C9D
      Japanese individuals were elucidated using an exon-specific PCR-SSCP method
      followed by direct sequencing of the target exons.

PMID- 10072635
TI  - Reference typing report for complement component C4.
AB  - During the 7th Complement Genetics Workshop, Mainz, Germany, May 1998, a
      complement component C4 typing exercise took place with the aim of applying
      present technologies to the definition of reference C4 alleles/phenotypes and the
      recognition of nonexpressed (Q0) C4 alleles within expressed haplotypes. Eleven
      samples were submitted from 3 laboratories and tested by 14 participating
      laboratories with basic protein-typing technologies; in addition, each laboratory
      contributed data from local expertise. The samples were introduced to the
      reference typing for one or more characteristic allotype or for partial or total
      nonexpression of one isotype. The blinded samples were centrally evaluated and
      the results discussed among the participants at a plenum meeting. From the
      results, the samples could be classified into a group of common, easy to diagnose
      pheno-/allotypes, less common but still unanimously recognised variants, and a
      third group with difficult pheno-/allotypes. Within the latter group, the
      allotypes were either new (C4A '92'; C4B '93') and/or showed partial or total
      reversed antigenicity and unusual Rodgers/Chido (Rg/Ch) PCR subtypes (C4A '92';
      C4A 12; C4B '35'; C4B '13'). Semiquantitative C4-alpha-chain estimates of
      relative isotype levels correlated well with the number of alleles seen at each
      locus by agarose gel electrophoresis, and were superior to other isotype
      quantitation methods. From the evaluation of the reference typing it was
      concluded that the recognition of rare, aberrant or hybrid C4 alleles with
      partial or total reversed Rg/Ch antigenicity or monoclonal reactivity is still
      difficult in most instances; besides isotype-dependent lysis, relative migration
      values, immunoblots with Rg- and Ch-specific monoclonal antibodies, Rg/Ch PCR
      typing, side-by-side comparison with already described allotypes will ultimately
      be required. The recognition of nonexpressed alleles within C4A and C4B expressed
      phenotypes remains the major obstacle in C4 genetic typing. Finally, a conclusive
      interpretation of DNA typing results will be achieved only in the context of
      complete allotyping results at the protein level, and at present cannot replace
      conventional protein allotyping.

PMID- 10072636
TI  - Reference typing report for complement factor B.
AB  - Factor B (BF) reference typing was carried out on the occasion of the VIIth
      Complement Genetics Workshop in Mainz, May 1998. Two different sets of samples
      were analysed by agarose electrophoresis and/or isoelectric focusing at the
      protein level, and by PCR-RFLP analysis at the DNA level. These results confirmed
      the reliability of the standard agarose electrophoresis technique for the
      identification of the major BF alleles as well as for the identification of
      cathodic and anodic variants. However, the exact alphanumeric designation of
      individual variants relative to the reference distance between alleles S and F1
      turned out to be more difficult. Using PCR-RFLP analysis, the common alleles F
      and S as well as the FA and FB subtypes in 6 samples containing an F allele were
      all assigned correctly. However, the variants F1 and S07 were not detected by
      this method, as they could not be distinguished from the accompanying S allele.
      Therefore, a combined application of all three typing methods is recommended for
      a reliable identification of factor B alleles, variants and FA/FB subtypes.

PMID- 10072637
TI  - Reference typing report for complement component C3.
AB  - A comparison of five C3 variant samples has been performed by conventional high
      voltage gel electrophoresis in three laboratories (Palermo, Berlin and Mainz).
      Local designation was shown within SD = +/-0.75 mm migration distance in the
      Mainz laboratory. Methodological modifications by laboratories were not accounted
      for (cooling temperature, relative mobilities between runs). In parallel, all
      reference samples were also sequenced after exon-specific amplification. As a
      result, two variants with identical final designations and two variants with
      different mobilities were shown to conform at the molecular basis exhibiting an
      amino acid exchange that causes the corresponding change in relative mobility as
      compared to normal C3F and C3S.

PMID- 10072638
TI  - Reference typing report for complement components C6, C7 and C9 including
      mutations leading to deficiencies.
AB  - The results of the present (VIIth Complement Genetics Workshop and Conference,
      Mainz, May 1998) and past reference typing workshops for the terminal complement
      components C6, C7 and C9 are compiled and discussed both on the protein level and
      on the DNA level. This report also focuses on the molecular bases of expressed
      and silent polymorphisms and reviews the molecular bases of subtotal and complete
      deficiencies of these proteins and their associations with protein and DNA
      markers. The results of the protein typing for C6 are published in the following
      paper of this issue.

PMID- 10072639
TI  - Reference typing report for complement component C6: protein typing.
AB  - Within the C6/C7/C9 Session of the VIIth Complement Genetics Workshop and
      Conference, various C6 protein allotypes collected from four laboratories were
      examined using polyacrylamide gel isoelectric focusing (PAGIF) followed by direct
      immunofixation. Nineteen different variants including 17 recognized allotypes and
      introducing two new allotypes were distinguished besides the two common allotypes
      C6 A and C6 B. They were designated basically according to the previous statement
      on C6 nomenclature. Details on C6 DNA markers and associations of C6 markers with
      deficiencies of terminal complement components are published in the preceding
      paper of this issue.

PMID- 10072640
TI  - Reference typing report for complement receptor 1 (CR1).
AB  - A total of 100 Chinese blood donors (50 from Shen-Zhen and 50 from Taiwan) were
      studied by the participants in addition to 9 reference samples. A new
      nomenclature for the CR1 structural alleles was recommended by the participants
      which would use a numbering system, e.g. CR1*1. The structural allele frequencies
      in the Chinese were: CR1*1 (190 kD) 0.96, CR1*2 (220 kD) 0.03, CR1*3 (160 kD)
      0.01 and CR1*4 (250 kD) 0.00. The HindIII expression polymorphism was also
      studied and the high expressing allele had a gene frequency of 0.71 while the low
      expressor gene frequency was 0.28. Erythrocyte copy numbers were quantified and
      compared between laboratories with good correlation (R = 0.55-0.88). The mean (+/
      SD) erythrocyte copy number was 463 (+/- 229) in the Taiwan donors and 446 (+/-
      207) in the Mainland Chinese.

PMID- 10072641
TI  - Analysis of umbilical artery flow parameters during fetal variable decelerations
      using computerized Doppler waveforms.
AB  - Umbilical artery velocity waves were obtained by Doppler ultrasonography before,
      during, and after 20 episodes of fetal heart rate (FHR) variable decelerations
      (VD) during the active stage of labor in 8 women. During 50% of the VD periods,
      the umbilical artery resistance flow parameters increased significantly (p <
      0.01). The increase in resistance preceded the decrease in FHR in six episodes
      (30%) of VD (AR-VD group; arterial resistance VD) and did not precede the change
      in FHR in another ten episodes (50%) of VD (VR-VD group; venous resistance VD).
      In the AR-VD group the FHR accelerations occurred before the decelerations in
      only 1 case (17%), while in the VR-VD group FHR accelerations preceded the
      decelerations in 8 out of the 10 episodes (80%). Using these Doppler studies, it
      may be possible to differentiate between two groups of VD: AR-VD - which are
      caused by umbilical artery occlusion and thus preceded by a measurable increase
      in umbilical artery resistance - and VR-VD - which are not preceded by a
      measurable increase in umbilical artery resistance and may be caused by fetal
      hypoxia.

PMID- 10072642
TI  - Lethal congenital dyserythropoietic anaemia type I in siblings presenting as
      pericardial effusions in the second trimester.
AB  - Congenital dyserythropoietic anaemias (CDA) are rare inherited disorders of
      erythropoiesis characterised by abnormal red cell morphology and haemolysis. The
      diagnosis of CDA should be considered in the fetus or patient presenting with a
      normocytic or macrocytic anaemia especially if red cell morphology is abnormal.
      Three types and other possible variants have been described. There are few
      reports of clinical presentation of CDA in utero. We present 2 cases of lethal
      CDA in siblings that presented with pericardial effusions in the second
      trimester.

PMID- 10072643
TI  - Detection of trisomy 18 by double screening in a low-risk pregnant population.
AB  - OBJECTIVE: A combination of low concentrations of maternal serum alpha
      fetoprotein (MSAFP) and human chorionic gonadotropin (hCG) was used to screen for
      trisomy 18 in early 2nd-trimester pregnancies in a low-risk child-bearing
      population. METHODS: Women less than 37 years of age were offered screening
      between 15 and 20 weeks of gestation. Those pregnancies showing low
      concentrations of MSAFP (<0. 75 multiples of the median) and hCG (<0.5 multiples
      of the mean) were considered positive. If gestational age was confirmed, genetic
      counselling and invasive prenatal diagnosis were offered. RESULTS: Between
      January 1995 and December 1996, 19,491 women were screened, of whom 252 were
      found to be positive (1.25%). 145 invasive procedures were carried out, and 3
      cases were detected. The odds of a fetus being affected after a positive screen
      result were 1 in 36. CONCLUSIONS: Measurement of low concentrations of MSAFP and
      hCG in pregnant women less than 37 years of age is an effective screening test
      for Edward's syndrome, but with regard to the natural history of this genetic
      condition, it can result in overuse of invasive tests which in turn can harm
      chromosomally normal pregnancies. This stresses the need to evaluate these
      pregnancies further with detailed ultrasonographic assessment and selective fetal
      karyotyping only.

PMID- 10072644
TI  - Contribution of tridimensional sonography and magnetic resonance imaging to
      prenatal diagnosis of Apert syndrome at mid-trimester.
AB  - A diagnosis of Apert syndrome, suspected at 24 weeks' gestation after
      conventional sonography showing turribrachycephaly and syndactyly of hands and
      feet, was confirmed at 26 weeks' gestation by tridimensional sonography and
      magnetic resonance imaging. This is only the second prenatal diagnosis reported
      at mid-trimester, excluding cases published from affected mothers or in
      connection with a context of recurrence. Additional findings have been collected
      from tridimensional sonography (mid-facial hypoplasia, downslanting palpebral
      fissures) and from magnetic resonance imaging (verticalization of the clivus and
      flattened angle of the cranial base).

PMID- 10072645
TI  - Contraction of the fetal ductus arteriosus induced by diclofenac. Case report.
AB  - The ductus arteriosus in the fetus may contract after administration of
      nonsteroidal anti-inflammatory drugs such as indomethacin and aspirin. We report
      a similar effect observed after a 36-week pregnant women was given diclofenac
      against flank pains. The ductus of this fetus was vasoconstricted with evidence
      of right ventricular hypertension. It resolved after cessation of the drug.
      Diclofenac is a cyclo-oxygenase inhibitor and thus carries the pharmacodynamic
      properties of other nonsteroidal anti-inflammatory drugs with inhibition of
      prostaglandin synthesis, resulting in vasoconstriction of the ductus arteriosus.
      We suggest monitoring of the fetal ductus state and velocities by fetal
      echocardiography in women treated with diclofenac.

PMID- 10072646
TI  - Management and outcome of fetomaternal Rh alloimmunization in twin pregnancies.
AB  - Between 1987 and 1996, nine twin pregnancies with fetomaternal Rh
      alloimmunization were delivered at our institution. Eight pregnancies were
      dizygotic, and the fetal blood groups were different in 3 cases. The remaining
      pregnancy was monozygotic and monochorionic-diamniotic. Intravenous fetal
      exchange transfusion was performed in five pregnancies, up to five times in each
      twin in one pregnancy. No fetal death occurred. The average gestational age at
      birth was 35 (range 33-37) weeks. The hemoglobin level was 13.2 (range 9.2-16.5)
      g/dl. Fetomaternal Rh alloimmunization in twin pregnancy is according to
      zygosity; each fetus has to be treated separately, except in case of
      transplacental communication.

PMID- 10072647
TI  - Assessment of triplet fetal growth by using cross-sectional analysis of the birth
      weight.
AB  - OBJECTIVE: To model the growth of triplets. METHOD: Statistical analysis using
      data of a consecutive series of 76 triplet gestations (223 livebirths). RESULTS:
      The best model to describe the growth was linear regression (r = 0.76; r2 =
      0.577; p < 0.0001; y = -2,858.05 + 139.66x). 34.2% of the sets had an
      intratriplet discordance rate of at least 25%, and 11.8% of the triplets had a
      maximum discordance rate over 40%. CONCLUSIONS: (1) Triplet fetal growth is
      strongly related to the gestational age; (2) the growth of each triplet in a same
      set may considerably differ, and (3) the use of singleton curves for triplet
      growth assessment is inadequate.

PMID- 10072648
TI  - Extra euchromatic band in the qh region of chromosome 9.
AB  - Chromosomal analysis of amniotic cell culture revealed an extra euchromatic band
      in the variable heterochromatin region 9q12. Cytogenetic analysis of the fetus
      was compared with the chromosomes of the parents. Using different cytogenetic
      banding techniques and fluorescence in situ hybridization with specific DNA
      probes, the structural rearrangements involved were considered. The very rare
      variant proved to be familial. Demonstrating the inheritance of a normal
      individual supports the interpretation of the prenatal analysis of chromosome 9
      as a variant without clinical relevance for the fetus.

PMID- 10072649
TI  - Early transvaginal measurement of cephalic index for the detection of down
      syndrome fetuses.
AB  - OBJECTIVE: The aim of this study was to produce normal cephalic index values by
      transvaginal scan early in pregnancy and to evaluate the screening utility of
      this measurement for the identification of fetuses at risk for Down syndrome.
      METHOD: In this prospective cross-sectional study, transvaginal high-resolution
      sonography was performed between 9 and 16 weeks of gestation in 1,087 euploid
      fetuses and 36 Down syndrome fetuses. Measurements of the cephalic index,
      calculated as the ratio biparietal diameter/occipito-frontal diameter, were
      plotted against gestational age. RESULTS: The cephalic index was found to show
      fairly constant values throughout the period evaluated. The best correlation with
      gestational age was described by a linear correlation. All the measurements
      obtained in Down syndrome fetuses were within the normal ranges. CONCLUSION: Our
      data show that in early pregnancy the cephalic index cannot be considered a
      useful tool in the detection of fetuses at risk for Down syndrome.

PMID- 10072650
TI  - Variability of adjustments to indices in determining patient risk in biochemical
      screening.
AB  - It has long been appreciated that the measurement of biochemical parameters for
      prenatal screening for neural tube defects, and later aneuploidy, is not as
      simple as measuring hemoglobin or hematocrit. Early in the game, it was
      recognized that there are gestational age curves, and that since alpha
      fetoprotein (AFP), for example, is a fetal product, its distribution varies as a
      function of maternal plasma volume, and therefore the weight of the mother. A
      number of different adjustment factors have been used for AFP and other
      parameters for years, with varying degrees of consistency and reliability. Here
      we review a number of adjustments that have been used, and try to give priority
      to those that have been most effective. Furthermore, laboratories and programs
      need to be cognizant that with newer parameters being added, the specifics of
      requirements will vary on a case-by-case parameter basis, and optimal screening
      can only be achieved with the appropriate adjustments.

PMID- 10072652
TI  - Acardiac twins: pathophysiology, diagnosis, outcome and treatment. Six cases and
      review of the literature.
AB  - Twin gestation is often a hazardous pregnancy and especially the monochorionic
      twin pregnancy significantly contributes to fetal morbidity and mortality. Among
      the serious complications with twins, the twin-twin transfusion syndrome
      complicates 5-35% of monozygotic twin pregnancies with monochorionic
      placentation. Acardiac twinning, earlier known as chorioangiopagus parasiticus,
      is the most extreme manifestation of this condition. An acardiac twin is a rare
      complication of multifetal pregnancy, in the literature reported at an incidence
      of 1% of monochorionic twin pregnancies, i.e. 1 of 35,000 pregnancies. In the
      following paper we review the literature on the subject and report 6 cases, 5
      twins and 1 triplet, that were diagnosed at our department during the period of
      1993-1997 and treated conservatively. Only 1 child survived.

PMID- 10072651
TI  - Prenatal diagnosis of congenital neuroblastoma. Analysis of 4 cases and review of
      the literature.
AB  - OBJECTIVE: Advances in prenatal diagnostics during the last 10 years have enabled
      the examiner to detect even rare fetal disorders such as fetal tumours.
      Congenital neuroblastoma is the most frequent solid neoplasm in infancy, with a
      retroperitoneal cystic or solid mass being a sonographic sign of the conditions.
      METHODS: We present 4 cases of neuroblastoma showing suspicious prenatal
      ultrasound findings. The investigation comprises detection during pregnancy,
      typical sonographic signs, as well as the postnatal outcome. In addition, a
      review of the literature is undertaken with a focus on prenatal sonographic signs
      of congenital neuroblastomas. RESULTS: In all 4 cases, a cystic tumour was
      detected during the 3rd trimester of pregnancy by means of B-mode sonography. One
      boy died of disseminated metastases at the age of 26 months. The other 3 survived
      after surgery and have remained healthy. CONCLUSIONS: The detection of a cystic
      suprarenal mass is suspicious of a congenital neuroblastoma. The delivery should
      take place at a perinatal centre.

PMID- 10072653
TI  - Evolution of left ventricular diseasein the fetus. Case report.
AB  - A fetal case is described that showed a rapid progression from the features of
      initial left ventricular fibroelastosis at 20 weeks of gestation to a more marked
      dilation at 22 weeks and finally to a hypoplastic left ventricle with aortic
      stenosis at 24 weeks of gestation. This case confirms the evolutive character of
      left ventricular disease during fetal life.

PMID- 10072660
TI  - Variations in CSF monoamine metabolites according to the season of birth.
AB  - The cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5
      hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) as well as their ratios and correlations were analyzed
      in relation to the season of birth. The sample consisted of 241 drug-free
      patients participating in psychobiological programs and comprising the DSM-III-R
      diagnoses of mood, anxiety and adjustment disorders. Significant season-of-birth
      variations were found even after adjusting for sex, age, height, the diagnostic
      category and the month of lumbar puncture. Those born during February to April
      had significantly lower values of 5-HIAA. Values of HVA and of the ratios HVA/5
      HIAA and HVA/MHPG were significantly higher for those born during October to
      January. Correlation coefficients also showed season-of-birth variations. These
      results may provide an important link for the season-of-birth variations reported
      for several neuropsychiatric disorders.

PMID- 10072661
TI  - High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely
      depressed patients.
AB  - Calcium (Ca) and magnesium (Mg) are involved in many processes related to
      depression. Evaluations of serum and plasma Ca and Mg levels in depressive
      disorders do not show consistent results. The few studies that examined their
      cerebrospinal fluid (CSF) levels tended to find no differences between depressed
      patients and controls. Because both hypercalcemia and hypomagnesemia are
      associated with depression, and as Mg may function as a Ca antagonist, it is
      suggested that the relationship between these cations could be different in
      depressed patients and controls. We examined CSF and serum Ca and Mg in acutely
      depressed patients diagnosed as having major depressive disorder or being in a
      depressive episode of bipolar disorder. Controls were subjects undergoing lumbar
      puncture as part of an evaluation for headache or suspected meningitis and found
      to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were
      found to be elevated in the depressed patients compared with the controls. A
      retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg
      does not seem to refute the findings of this study. We further discuss our
      findings in their relation to the acuteness of the depressive disorders.

PMID- 10072662
TI  - Suicidal behavior in depression: relationship to platelet serotonin transporter.
AB  - OBJECTIVE: Suicidal behavior in depressed patients is associated with low central
      serotonin. Thus, platelet serotonin uptake in relation to suicidal behavior in
      depression was examined. METHODS: Depressed patients who had never attempted
      suicide (n = 23) were compared with depressed patients who had never attempted
      suicide (n = 26) and normal controls (n = 71) for platelet serotonin uptake.
      RESULTS: Depressed patients who had a lifetime history of a suicide attempt had a
      significantly greater apparent Michaelis constant (Km) of platelet serotonin
      uptake than either depressed patients who had never attempted suicide or
      controls. Patients rated high for current suicidal ideation at the index
      admission had significantly higher Km values than patients rated low. Also,
      patients who reattempted or committed suicide during a 5-year follow-up period
      had significantly higher Km values than controls. Among women patients who had
      attempted suicide there was a significant correlation between extrapunitive
      hostility scores and Km values. CONCLUSION: The serotonin transporter warrants
      further study in relation to suicidal behavior in depression.

PMID- 10072663
TI  - The electrically elicited startle blink reflex in patients with schizophrenia: A
      threshold study of different reflex components.
AB  - The electrically elicited blink reflex consists of three components (R1, R2, R3).
      In humans the excitability of these components is influenced by attentional
      states. In particular, distraction from the stimulus leads to facilitation of the
      bilateral R2 and R3. The present study was performed in order to investigate the
      excitability of the different components of the electrically evoked blink reflex
      in 13 patients with schizophrenia and 13 normal controls under standard
      conditions. Therefore, the thresholds of the distinct components were determined
      without any inhibitory or facilitatory procedure. There was no significant
      difference in R1 and R2 thresholds between patients and controls. In contrast,
      the R3 threshold was significantly reduced in schizophrenic patients (R3
      threshold = 17.5 mA in normal subjects, 10.5 mA in patients, p = 0. 0001). In
      recent studies the R3 magnitude was found to be highly susceptible to changes in
      the attentional state of normal subjects. The lower threshold of R3 in patients
      with schizophrenia might therefore be a neurophysiological marker of attentional
      dysfunctions in schizophrenia.

PMID- 10072664
TI  - Comparison of risperidone and mosapramine addition to neuroleptic treatment in
      chronic schizophrenia.
AB  - There is little information regarding the effects of risperidone addition to
      neuroleptic treatment in chronic schizophrenia. As a preliminary study, 10
      neuroleptic-treated schizophrenic inpatients received risperidone (high 5HT2A/D2
      ratio, i.e. the ratio between 5HT2A and D2 receptor occupancy) and mosapramine
      (low 5HT2A/D2 ratio) in a randomized, single-blind, crossover, add-on study
      consisting of 8 weeks of treatment each with risperidone and mosapramine.
      Although both additions resulted in significant, albeit modest, improvement,
      there was no significant difference in the scores on the Positive and Negative
      Syndrome Scale for Schizophrenia between risperidone and mosapramine addition.
      These results suggest that risperidone and mosapramine bring about comparable
      effects in add-on design. Thus, risperidone with a high 5HT2A/D2 ratio does not
      seem to be better than mosapramine with a low 5HT2A/D2 ratio when combined with
      conventional neuroleptics. Further studies including a large number of patients
      and a double-blind design are needed.

PMID- 10072666
TI  - IPEG guideline on statistical design and analysis for pharmacodynamic trials.
      International Pharmaco-EEG Group.

PMID- 10072665
TI  - Chronic oral haloperidol and clozapine in rats: A behavioral evaluation.
AB  - The present study evaluated chronic oral treatment of rats with haloperidol or
      clozapine. Drugs were given in the drinking water for a 23-day period. Rat
      behavior was analyzed once a week in an open field. Rats ingested either 1.7
      mg/kg haloperidol or 40 mg/kg clozapine daily. Blood serum analysis revealed
      concentrations of 6 ng/ml for haloperidol and 22 ng/ml for clozapine at the end
      of the treatment. Haloperidol decreased overall activity from the onset of
      treatment. Clozapine showed similar effects only on the last test day. Control
      animals showed a slight habituation in exploration-related parameters. In
      conclusion, these results indicate that oral drug administration through the
      drinking water is a suitable mode of noninvasive chronic treatment that led to
      sufficiently high drug levels to induce specific pharmacological effects in rats.

PMID- 10072667
TI  - Effect of two antidepressant drugs on REM sleep and EMG activity during sleep.
AB  - In a placebo-controlled study, the effects on sleep of single and repeated doses
      of imipramine and dexnafenodone, an antidepressant drug under development, were
      investigated in young, healthy volunteers. In contrast to placebo, both drugs
      suppressed REM sleep substantially after acute and repeated administration. As a
      consequence, REM sleep latencies increased under active treatment to mean values
      which were about two to four times larger than baseline values. Since the active
      inhibition of the muscle tone is a distinct feature of REM sleep, we studied the
      influence of the two antidepressant drugs on this variable. By means of
      computerised EMG analysis, tonic and transient EMG activity were computed for
      total recording time and for the different sleep stages. While tonic EMG activity
      during sleep was increased with both drugs, transient EMG events remained
      unaffected. Computerised analysis of the microstructure of sleep is an effective
      tool for studying the effect of antidepressant drugs on sleep.

PMID- 10072668
TI  - Spectral structure and brain mapping of human alpha activities in different
      arousal states.
AB  - In a study with 10 young, healthy subjects, alpha activities were studied in
      three different arousal states: eyes closed in relaxed wakefulness (EC),
      drowsiness (DR), and REM sleep. The alpha band was divided into three
      subdivisions (slow, middle, and fast) which were analyzed separately for each
      state. The results showed a different spectral composition of alpha band
      according to the physiological state of the subject. Slow alpha seemed to be
      independent of the arousal state, whereas middle alpha showed a difference
      between REM and the other states. The fast-alpha subdivision appears mainly as a
      waking EEG component because of the increased power displayed only in wakefulness
      and lower and highly stable values for DR and REM. Scalp distribution of alpha
      activity was slightly different in each state: from occipital to central regions
      in EC, this topography was extended to fronto-polar areas in DR, with a
      contribution from occipital to frontal regions in REM sleep. These results
      provide evidence for an alpha power modulation and a different scalp distribution
      according to the cerebral arousal state.

PMID- 10072669
TI  - Comparison of actual pallidotomy lesion location with expected stereotactic
      location.
AB  - Accuracy of pallidotomy lesion placement was assessed by comparing actual lesion
      locations with expected pallidotomy lesion locations based on stereotaxy. Actual
      and expected lesions were compared in anteroposterior, dorsoventral and lateral
      axes. In 22 pallidotomies, actual lesion locations were determined using axial MR
      images. Expected lesion locations were calculated using a starting point derived
      from preoperative computerized tomography, displacements from the starting point
      based on microelectrode-driven electrophysiological refinement, and the
      trajectory angle of the lesioning tract relative to the anterior-posterior
      commissural plane. On average, actual lesion locations were found 2.91 +/- 2.23
      mm posterior, 3.22 +/- 2.49 mm ventral, and 0.05 +/- 1.80 mm lateral compared to
      the expected lesion location. Discrepancies between the actual lesion and
      expected lesion locations may be mostly accounted for by posterior and ventral
      lesion spread from the exposed electrode tip, in-plane and volume averaging
      effects associated with MR images, and possible brain shifting during surgery.
      However, despite the remaining small differences between actual and expected
      lesion location, good clinical outcome of reduced dyskinesias and 'off' time
      along with UPDRS-based improvement in mentation, motor and activity of daily
      living measures was observed.

PMID- 10072670
TI  - Neuronal activity in GP and Vim of parkinsonian patients and clinical changes of
      tremor through surgical interventions.
AB  - Microrecordings were performed during pallidotomy and thalamotomy for Parkinson's
      disease (PD). Neuronal activity in globus pallidus (GP) was in general agreement
      with previous studies of human and primate models of PD. Neuronal activity, where
      frequency of tremor appeared to oscillate independently from peripheral input,
      was encountered in GPi. In contrast, neuronal activity in Vim regarding frequency
      of firing also correlated with tremor and was passively driven by kinesthetic
      stimuli with a somatotopic arrangement. Pallidal lesions based on microrecording
      induced relative reductions of tremor, while small Vim lesions immediately
      alleviated tremor. Basal ganglia pathology due to dopamine depletion could
      generate oscillatory neuronal activity in GPi, which may cause tremor. However,
      peripheral feedback to the motor cortex via Vim is also significant for
      tremorgenesis, because Vim may be an excitatory driving source for motor cortical
      neurons. Thus, a Vim lesion could reduce excitability of the motor cortical
      neurons and abolish tremor.

PMID- 10072671
TI  - An algorithm for the empirical determination of intracranial stereotactic
      targets.
AB  - The determination of empirical targets for functional brain lesions is usually
      made with graphical techniques using CT or MR software. Geometrical errors occur
      in the method when the intercommissural line and plane of the third ventricle are
      not parallel and orthogonal to transaxial images. A mathematical algorithm can be
      used to calculate target coordinates from the coordinates of the anterior
      commissure, the posterior commissure, and the position of a third point within
      the inferior, third ventricle. These coordinates may be determined in any image
      plane in stereotactic space. By supplying the distance of the target from the mid
      point of the intercommissural line, the distance lateral and inferior to the
      line, target coordinates are computed. This overcomes geometrical errors of
      previous graphical methods.

PMID- 10072672
TI  - Stereotactic biopsy of intracranial brain lesions. High diagnostic yield without
      increased complications: 65 consecutive biopsies with early postoperative CT
      scans.
AB  - Diagnostic yield and complication rate were analyzed for a series of 65
      consecutive stereotactic biopsies of intra-axial brain lesions. The diagnostic
      yield was 98.5 +/- 1.5% and the complication rate was 1.5%. A median number of 14
      biopsies (range 1-48) were taken per lesion. The biopsy sites followed a
      clockwise pattern, going from the superficial margin to the center and the deep
      margin of the lesion with respect to the inner table of the skull. A side window
      cannula biopsy needle was used. All patients underwent immediate postoperative CT
      scans within 4 h of biopsy to rule out intracranial complications. All patients
      were discharged within 24 h after biopsy, unless medical reasons unrelated to the
      biopsy required further hospitalization. We attribute the high diagnostic yield
      in our series to the high number of systematically taken biopsies per lesion. The
      higher number of biopsies did not lead to an increase in complications. From our
      experience, it appears safe to discharge patients the same day or within 24 h
      after a stereotactic biopsy if the postoperative CT shows no complication.
      Stereotactic biopsy could often safely be performed on an outpatient basis.

PMID- 10072674
TI  - Correction: Case Records of the Massachusetts General Hospital (Case 3-1999).

PMID- 10072673
TI  - LINAC radiosurgery for cavernous sinus meningiomas.
AB  - Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors.
      Since 1989, 24 patients with cavernous sinus meningiomas have been treated at
      Stanford University Medical Center with linear accelerator (LINAC) radiosurgery.
      The mean age of the patients was 47.8 years (range 28-78). The mean volume
      treated was 6. 83 cm3 (range 0.45-22.45 cm3), covered with an average of 2.3
      isocenters (range 1-5). Radiation dose averaged 17.7 Gy (range 14-20 Gy). This
      group of patients was retrospectively studied by sending clinical questionnaires
      to both the patient/family and referring physicians, and reviewing clinic charts.
      In addition, follow-up imaging studies were obtained to measure residual tumor
      volume. Follow-up averaged 45.6 months (range 19-80). Tumor control
      (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage
      in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on
      MRI imaging 1-3 years after radiosurgery. Neurologic status was improved in 10
      patients (42%) and unchanged in 12 patients (50%). There was 1 case of
      symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All
      other complications were transient, including 4 cases of trigeminal hypesthesia
      and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was
      100%. Although follow-up is still short, this experience corroborates prior
      reports that radiosurgery can be used to treat selected small cavernous sinus
      meningiomas with good to excellent clinical results and minimal morbidity.

PMID- 10072675
TI  - Discovery of 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-
      pyridazinebutanoic acid (FK 838): a novel non-xanthine adenosine A1 receptor
      antagonist with potent diuretic activity.

PMID- 10072676
TI  - Acquisition of high-affinity, SH2-targeted ligands via a spatially focused
      library.

PMID- 10072677
TI  - Studies on the mode of action of mitomycin C(7) aminoethylene disulfides (BMS
      181174 and KW-2149): reactivity of 7-N-(mercaptoethyl)mitomycin C.

PMID- 10072678
TI  - A general and fast scoring function for protein-ligand interactions: a simplified
      potential approach.
AB  - A fast, simplified potential-based approach is presented that estimates the
      protein-ligand binding affinity based on the given 3D structure of a protein
      ligand complex. This general, knowledge-based approach exploits structural
      information of known protein-ligand complexes extracted from the Brookhaven
      Protein Data Bank and converts it into distance-dependent Helmholtz free
      interaction energies of protein-ligand atom pairs (potentials of mean force,
      PMF). The definition of an appropriate reference state and the introduction of a
      correction term accounting for the volume taken by the ligand were found to be
      crucial for deriving the relevant interaction potentials that treat solvation and
      entropic contributions implicitly. A significant correlation between experimental
      binding affinities and computed score was found for sets of diverse protein
      ligand complexes and for sets of different ligands bound to the same target. For
      77 protein-ligand complexes taken from the Brookhaven Protein Data Bank, the
      calculated score showed a standard deviation from observed binding affinities of
      1.8 log Ki units and an R2 value of 0.61. The best results were obtained for the
      subset of 16 serine protease complexes with a standard deviation of 1.0 log Ki
      unit and an R2 value of 0.86. A set of 33 inhibitors modeled into a crystal
      structure of HIV-1 protease yielded a standard deviation of 0.8 log Ki units from
      measured inhibition constants and an R2 value of 0.74. In contrast to empirical
      scoring functions that show similar or sometimes better correlation with observed
      binding affinities, our method does not involve deriving specific parameters that
      fit the observed binding affinities of protein-ligand complexes of a given
      training set. We compared the performance of the PMF score, Bohm's score (LUDI),
      and the SMOG score for eight different test sets of protein-ligand complexes. It
      was found that for the majority of test sets the PMF score performs best. The
      strength of the new approach presented here lies in its generality as no
      knowledge about measured binding affinities is needed to derive atomic
      interaction potentials. The use of the new scoring function in docking studies is
      outlined.

PMID- 10072679
TI  - Non-peptide corticotropin-releasing hormone antagonists: syntheses and structure
      activity relationships of 2-anilinopyrimidines and -triazines.
AB  - Screening of our chemical library using a rat corticotropin-releasing hormone
      (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly
      displaced [125I]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to
      the known peptide antagonist alpha-helical CRH(9-41) (Ki = 5700 nM vs 1 nM).
      Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in
      the same tissue, but it was less potent than alpha-helical CRH(9-41) (IC50 = 20
      000 nM vs 250 nM). Systematic structure-activity relationship studies, using the
      cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding
      to hCRH1 receptors. Several high-affinity 2-anilinopyrimidines and -triazines
      were discovered, some of which had superior pharmacokinetic profiles in the rat.
      This paper describes the structure-activity studies which improved hCRH1 receptor
      binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean
      hCRH1 Ki = 32 nM) had a significantly improved pharmacokinetic profile in the rat
      (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral
      bioavailability at 5 mg/kg) relative to the early lead structures.

PMID- 10072680
TI  - Corticotropin-releasing hormone receptor antagonists: framework design and
      synthesis guided by ligand conformational studies.
AB  - As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42),
      anilinopyrimidines I were identified as potent antagonists of corticotropin
      releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing
      factor, CRF1-R). Our next goal was to understand the receptor-bound conformation
      of the antagonists and to use this information to help guide preclinical
      optimization of the series and to develop new leads. Since receptor structural
      information was not available, we assumed that these small, high-affinity
      antagonists would tend to bind in conformations at or energetically close to
      their global minima and that rigid analogues that maintained the important
      stereoelectronic features of the bound anilinopyrimidine would also bind tightly.
      Conformational preferences and barriers to rotation of the anilinopyrimidines
      were determined by semiempirical methods, and X-ray and variable-temperature NMR
      spectroscopy provided experimental results that correlated well with calculated
      structures. Using these data, a key dihedral angle was constrained to design
      fused-ring analogues, substituted N-arylpyrrolopyridines II, synthesis of which
      provided CRH1 receptor antagonists with potency equal to that of the initial
      congeneric leads (Ki = 1 nM) and which closely matched the conformation held by
      the original compound, as determined by crystallography. In addition to providing
      a useful template for further analogue synthesis, the study unequivocally
      determined the active conformation of the anilinopyrimidines. Theoretical and
      spectroscopic studies, synthesis, and receptor binding data are presented.

PMID- 10072681
TI  - Synthesis, corticotropin-releasing factor receptor binding affinity, and
      pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and 
      pyridines.
AB  - The synthesis and CRF receptor binding affinities of several new series of N
      aryltriazolo- and -imidazopyrimidines and -pyridines are described. These
      cyclized systems were prepared from appropriately substituted diaminopyrimidines
      or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations
      of amino (ether) pendants and aromatic substituents have defined the structure
      activity relationships of these series and resulted in the identification of a
      variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and
      lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were
      initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability,
      high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted
      further PK studies in the dog following both iv and oral routes of
      administration. Results from this work indicated 4i,x had properties we believe
      necessary for a potential therapeutic agent, and 4i1 has been selected for
      further pharmacological studies that will be reported in due course.

PMID- 10072682
TI  - Bisquaternary ligands of the common allosteric site of M2 acetylcholine
      receptors: search for the minimum essential distances between the pharmacophoric
      elements.
AB  - Structurally diverse molecules, such as alcuronium, gallamine, and tubocurarine
      as well as W84 and WDUO, are known to interact allosterically with ligand binding
      to muscarinic M2 acetylcholine receptors. Preliminary molecular modeling studies
      revealed two positive charges in the middle and two lateral aromatic areas to be
      essential elements of a high allosteric potency. To find out the optimum
      distances between these pharmacophoric elements, a systematic variation of the
      spacer in the series of W84, WDUO, and IWDUO compounds was performed. The
      allosteric reduction of the rate of dissociation of the antagonist [3H]-N
      methylscopolamine from porcine heart M2 receptors served as a test system. The
      minimal essential distance between the positive charges was found to be 10 A. The
      length of the peripheral spacers connecting the positive charge and the lateral
      aromatic moiety appears to depend on the chemical functionality; the peripheral
      spacers have to be long and flexible enough to position the aromatic skeletons in
      the spatial neighborhood of the alkane middle chain: in the case of an oxime
      ether containing peripheral spacer, six atoms are required, and in the case of an
      alkane chain, four carbon atoms are necessary to adopt the pharmacophoric S-shape
      conformation.

PMID- 10072684
TI  - Prediction of the binding free energies of new TIBO-like HIV-1 reverse
      transcriptase inhibitors using a combination of PROFEC, PB/SA, CMC/MD, and free
      energy calculations.
AB  - We have ranked 13 different TIBO derivatives with respect to their relative free
      energies of binding using two approximate computational methods: adaptive
      chemical Monte Carlo/molecular dynamics (CMC/MD) and Poisson-Boltzmann/solvent
      accessibility (PB/SA) calculations. Eight of these derivatives have
      experimentally determined binding affinities. The remaining new derivatives were
      constructed based on contour maps around R86183 (8Cl-TIBO), generated with the
      program PROFEC (pictorial representation of free energy changes). The rank order
      among the derivatives with known binding affinity was in good agreement with
      experimental results for both methods, with average errors in the binding free
      energies of 1. 0 kcal/mol for CMC/MD and 1.3 kcal/mol for the PB/SA method. With
      both methods, we found that one of the new derivatives was predicted to bind 1-2
      kcal/mol better than R86183, which is the hitherto most tightly binding
      derivative. This result was subsequently supported by the most rigorous free
      energy computational methods: free energy perturbation (FEP) and thermodynamic
      integration (TI). The strategy we have used here should be generally useful in
      structure-based drug optimization. An initial ligand is derivatized based on
      PROFEC suggestions, and the derivatives are ranked with CMC/MD and PB/SA to
      identify promising compounds. Since these two methods rely on different sets of
      approximations, they serve as a good complement to each other. Predictions of the
      improved affinity can be reinforced with FEP or TI and the best compounds
      synthesized and tested. Such a computational strategy would allow many different
      derivatives to be tested in a reasonable time, focusing synthetic efforts on the
      most promising modifications.

PMID- 10072683
TI  - Synthesis and biological evaluation of 2',3'-didehydro-2',3'- dideoxy-5
      fluorocytidine (D4FC) analogues: discovery of carbocyclic nucleoside
      triphosphates with potent inhibitory activity against HIV-1 reverse
      transcriptase.
AB  - The discovery of a novel cytosine nucleoside, beta-D-2', 3'-didehydro-2',3'
      dideoxy-5-fluorocytidine (D-D4FC), as a potent antihuman immunodeficiency virus
      (HIV) agent led us to synthesize a series of analogues and derivatives of beta-D
      D4FC that could be more selective and also possess increased glycosidic bond
      stability. The synthesized D-D4FC analogues were evaluated for anti-HIV-1
      activity, anticancer activity, and cytotoxicity in various cells. The biological
      data demonstrated that the 5-substitution of beta-D-D4FC with bromine (6c) and
      iodine (6d) resulted in the loss of antiviral activity, and the alpha-D anomer
      (7a) of D-D4FC was also devoid of activity. The 5-fluorouracil analogues (6b and
      7b) of D-D4FC were less potent and more cytotoxic than the parent compound,
      whereas the beta-L-D4FU (11) showed both potent anti-HIV-1 activity and
      cytotoxicity. N4- and 5'-O-acyl derivatives (17, 15a-c) of beta-D-D4FC exhibited
      comparable antiviral activity to beta-D-D4FC. In contrast, the N4-isopropyl
      derivative (20) of beta-D-D4FC was not active against HIV-1, even at 100 microM.
      The carbocyclic analogues (26a,b) of D4FC demonstrated weak activity against HIV
      1 and no toxicity in various cells. The triphosphates (27a,b) of the carbocyclic
      nucleosides demonstrated potent inhibitory activity against recombinant HIV-1
      reverse transcriptase at submicromolar concentrations. Of the compounds tested as
      potential anticancer agents, beta-D-, alpha-D-, and beta-L-D4FU (6b, 7b, 11)
      showed inhibitory activity against rat glioma and modest activity against human
      lung carcinoma, lymphoblastoid, and skin melanoma cells.

PMID- 10072685
TI  - Synthesis and pharmacology of site-specific cocaine abuse treatment agents: 2
      (aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane dopamine uptake
      inhibitors.
AB  - As part of a program to develop site-specific medications for cocaine abuse, a
      series of 2-(aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane derivatives
      was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and
      [3H]dopamine uptake assays using rat striatal tissue. Selected compounds were
      tested for their ability to substitute for cocaine in rat drug discrimination
      tests. Synthesis was accomplished by a series of Diels-Alder reactions, using cis
      and trans-cinnamic acid derivatives (nitrile, acid, acid chloride) with
      cyclohexadiene and cyclopentadiene. Standard manipulations produced the
      aminomethyl side chain. Many of the compounds bound with high affinity (median
      IC50 = 223 nM) to the cocaine binding site as marked by [3H]WIN 35,428. Potency
      in the binding assay was strongly enhanced by chlorine atoms in the 3- and/or 4
      position on the aromatic ring and was little affected by corresponding methoxy
      groups. In the [2.2.2] series there was little difference in potency between cis
      and trans compounds or between N, N-dimethylamines and primary amines. In the
      [2.2.1] series the trans exo compounds tended to be least potent against binding,
      whereas the cis exo compounds were the most potent (4-Cl cis exo: IC50 = 7.7 nM,
      27-fold more potent than 4-Cl trans-exo). Although the potencies of the bicyclic
      derivatives in the binding and uptake assays were highly correlated, some of the
      compounds were 5-7-fold less potent at inhibiting [3H]dopamine uptake than
      [3H]WIN 35,428 binding (for comparison, cocaine has a lower discrimination ratio
      (DR) of 2.5). The DR values were higher for almost all primary amines and for the
      trans-[2.2.2] series as compared to the cis-[2.2.2]. Most of the compounds had
      Hill coefficients approaching unity, except for the [2. 2.2] 3,4-dichloro
      derivatives, which all had nH values of about 2.0. Two of the compounds were
      shown to fully substitute for cocaine in drug discrimination tests in rats, and
      one had a very long duration of action.

PMID- 10072686
TI  - Substrate specificity and stereoselectivity of rat brain microsomal anandamide
      amidohydrolase.
AB  - Anandamide amidohydrolase (AAH) catalyzes the hydrolysis of
      arachidonylethanolamide (anandamide), an endogenous cannabinoid receptor ligand.
      To delineate the structural requirements of AAH substrates, rat brain microsomal
      AAH hydrolysis of a series of anandamide congeners was studied using two reverse
      phase high-performance liquid chromatography (RP-HPLC) assays developed in our
      laboratory. Arachidonamide (1) was found to be the best substrate with an
      apparent Km of 2.34 mM and a Vmax of 2.89 nmol/min/mg of protein. Although
      anandamide (2) has a similar Km value, its Vmax is approximately one-half that of
      arachidonamide. N, N-Bis(2-hydroxyethyl)arachidonamide (3) was not hydrolyzed,
      suggesting specificity for unsubstituted or mono-N-substituted arachidonamides.
      Analogues with a methyl group at the 1'-position of the ethanolamido headgroup
      were also found to have greater resistance to enzymatic turnover and therefore
      increased metabolic stability. The enzyme exhibited high stereoselectivity as the
      rate of hydrolysis of (R)-alpha-methanandamide (2.4%) (anandamide = 100%) was
      about 10-fold lower than that of its (S)-enantiomer (23%). In contrast, (R)-beta
      methanandamide was 6-times more susceptible (121%) than the (S)-beta-enantiomer
      (21%). Interestingly, an inverse correlation was shown between AAH
      stereoselectivity and the brain cannabinoid receptor affinity as the enantiomers
      with high receptor affinity displayed low susceptibility to hydrolysis by AAH.
      Metabolic stability is also imparted to analogues with a short hydrocarbon
      headgroup as well as to those possessing 2-monomethyl or 2,2-dimethyl
      substituents. 2-Arachidonylglycerol and racemic 1-arachidonylglycerol were shown
      to be excellent AAH substrates. To identify AAH inhibitors, hydrolysis of
      anandamide was also studied in the presence of a select group of cannabimimetics.
      Of these, (-)-Delta8-THC and SR141716A, a biarylpyrazole CB1 antagonist, were
      found to inhibit enzymatic activity. These newly defined enzyme recognition
      parameters should provide a foundation for the rational development of stable,
      therapeutically useful anandamide analogues with high receptor affinity.

PMID- 10072687
TI  - Design, synthesis, and structure-activity relationships of acetylene-based
      histamine H3 receptor antagonists.
AB  - New, potent, and selective histamine H3 receptor antagonists have been
      synthesized by employing the use of (1) an appropriately positioned nonpolar
      acetylene spacer group, (2) either a two-carbon straight chain linker or a
      conformationally restricting trans-cyclopropane ring between the C-4 position of
      an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational
      scheme for side-chain substitution for optimizing the hydrophobic domain.
      Compounds 9-18 are examples synthesized with the two-carbon straight chain
      linker, whereas 26-31 are analogues prepared by incorporation of the trans-(+/-)
      cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the
      (1R,2R)- and (1S, 2S)-cyclopropyl enantiomers of the most potent racemic compound
      31 (Ki = 0.33 +/- 0.13 nM) demonstrated a stereopreference in H3 receptor binding
      affinity for the (1R,2R) enantiomer 32 (Ki = 0.18 +/- 0.04 nM) versus the (1S,2S)
      enantiomer 33 (Ki = 5.3 +/- 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1
      ynyl)cyclopropyl)imidazole (32) is one of the most potent histamine H3 receptor
      antagonists reported to date.

PMID- 10072688
TI  - Identification of novel classes of protein kinase inhibitors using combinatorial
      peptide chemistry based on functional genomics knowledge.
AB  - A discovery approach based on an intramolecular inhibitory mechanism was applied
      to a prototype calmodulin (CaM)-regulated protein kinase in order to demonstrate
      a proof-of-principle for the development of selective inhibitors. The overall
      approach used functional genomics analysis of myosin light chain kinase (MLCK) to
      identify short autoinhibitory sequences that lack CaM recognition activity,
      followed by recursive combinatorial peptide library production and comparative
      activity screens. Peptide 18 (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2), one of
      several selective inhibitors discovered, has an IC50 = 50 nM for MLCK, inhibits
      CaM kinase II only at 4000-fold higher concentrations, and does not inhibit
      cyclic AMP-dependent protein kinase. Analogues of peptide 18 containing
      conformationally constrained cis-4-aminocyclohexanecarboxylic acid retained
      affinity and selectivity. The inhibitors add to the armamentarium available for
      the deconvolution of complex signal transduction pathways and their relationship
      to homeostasis and disease, and the approach is potentially applicable to enzymes
      in which the catalytic and regulatory domains are found within the same open
      reading frame of a cDNA.

PMID- 10072689
TI  - Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic
      airway responses.
AB  - Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator
      release, and apoptosis inhibition, and it plays a central role in inflammatory
      pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the
      Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1
      (CS-1) peptide of cellular fibronectin, are described that employ a novel N
      terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)
      fold more potent than the starting peptide and exhibited tight-binding properties
      (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent,
      small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold
      selective for the activated form of alpha4beta1, and it stimulated expression of
      ligand-induced epitopes on the integrin beta1 subunit, a property consistent with
      occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep
      with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses
      following antigen challenge and prevented development of nonspecific airway
      hyperresponsiveness to carbachol. These results show that highly selective and
      potent small-molecule antagonists can be identified to integrins with primary
      specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the
      generality of integrins as small molecule targets; and they validate alpha4beta1
      as a therapeutic target for asthma.

PMID- 10072690
TI  - Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and
      quinelorane.
AB  - In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and
      dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2
      selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring
      substituted derivatives had significant affinity for D2 receptors, albeit
      somewhat lower than the two parent compounds, 3 and 4. Compounds with N-propyl
      and N-allyl substituents (5b, 5c, 6c, and 6d) had higher affinity for the D2
      dopamine receptor than did their corresponding secondary amines (5a and 6a).
      Slightly different effects on affinity of an n-propyl and an n-allyl group in the
      new analogues of 3 and 4 suggest that different binding orientations may be
      invoked at the receptor.

PMID- 10072691
TI  - Hypoxia-selective nitrobenzyloxycarbonyl derivatives of 1,2-bis(methylsulfonyl)-1
      (2-chloroethyl)hydrazines.
AB  - Some 4- and 2-(nitrobenzyloxycarbonyl)-1, 2-bis(methylsulfonyl)-1-(2
      chloroethyl)hydrazines (4, 6, and 7) were synthesized and evaluated for their
      ability to exert preferential toxicity to hypoxic EMT6 mammary carcinoma cells
      using a colony-forming assay. Of these, the 4,5-dimethoxy-2-nitro analogue 6 (50
      microM, 1-h exposure) caused greater than 3 logs of kill of hypoxic cells, with
      relatively minor toxicity to corresponding aerobic cells. The ability of 4-nitro
      (4) and 4,5-dimethoxy-2-nitro (6) analogues to reach and kill hypoxic cells of
      solid tumors was also demonstrated using intradermally implanted EMT6 solid
      tumors in mice. In addition, a possible source of toxicity to normal tissue, i.
      e., the activation of the 4-nitrobenzyl derivative 4 by glutathione S-transferase
      catalyzed thiolysis, was essentially eliminated by replacing one of the benzylic
      methylene protons by a methyl group. The 4-nitro (4) and 4,5-dimethoxy-2-nitro
      (6) analogues also appear to be reduced more easily under acidic conditions (pH
      6.0) than under neutral conditions, as measured by differential pulse
      polarography. Since the pH in hypoxic regions is often lower than that in
      adjacent aerobic regions, this property should aid in the cytotoxic action of
      these agents against hypoxic cells of solid tumors.

PMID- 10072692
TI  - The link between brain learning, attention, and consciousness.
AB  - The processes whereby our brains continue to learn about a changing world in a
      stable fashion throughout life are proposed to lead to conscious experiences.
      These processes include the learning of top-down expectations, the matching of
      these expectations against bottom-up data, the focusing of attention upon the
      expected clusters of information, and the development of resonant states between
      bottom-up and top-down processes as they reach an attentive consensus between
      what is expected and what is there in the outside world. It is suggested that all
      conscious states in the brain are resonant states and that these resonant states
      trigger learning of sensory and cognitive representations. The models which
      summarize these concepts are therefore called Adaptive Resonance Theory, or ART,
      models. Psychophysical and neurobiological data in support of ART are presented
      from early vision, visual object recognition, auditory streaming, variable-rate
      speech perception, somatosensory perception, and cognitive-emotional
      interactions, among others. It is noted that ART mechanisms seem to be operative
      at all levels of the visual system, and it is proposed how these mechanisms are
      realized by known laminar circuits of visual cortex. It is predicted that the
      same circuit realization of ART mechanisms will be found in the laminar circuits
      of all sensory and cognitive neocortex. Concepts and data are summarized
      concerning how some visual percepts may be visibly, or modally, perceived,
      whereas amodal percepts may be consciously recognized even though they are
      perceptually invisible. It is also suggested that sensory and cognitive
      processing in the What processing stream of the brain obey top-down matching and
      learning laws that are often complementary to those used for spatial and motor
      processing in the brain's Where processing stream. This enables our sensory and
      cognitive representations to maintain their stability as we learn more about the
      world, while allowing spatial and motor representations to forget learned maps
      and gains that are no longer appropriate as our bodies develop and grow from
      infanthood to adulthood. Procedural memories are proposed to be unconscious
      because the inhibitory matching process that supports these spatial and motor
      processes cannot lead to resonance.

PMID- 10072693
TI  - Anesthesia and the electrophysiology of auditory consciousness.
AB  - Empirical work is reviewed which correlates the presence or absence of various
      parts of the auditory evoked potential with the disappearance and reemergence of
      auditory sensation during induction of and recovery from anesthesia. As a result,
      the hypothesis is generated that the electrophysiological correlate of auditory
      sensation is whatever neural activity generates the middle latency waves of the
      auditory evoked potential. This activity occurs from 20 to 80 ms poststimulus in
      the primary and secondary areas of the auditory cortex. Evidence is presented
      suggesting that earlier or later waves in the auditory evoked potential do not
      covary with auditory sensation (as opposed to auditory perception) and it is
      therefore suggested that they are possibly not the electrophysiological
      correlates of sensation.

PMID- 10072694
TI  - Simulating consciousness in a bilateral neural network: "nuclear" and "fringe"
      awareness.
AB  - A technique for the bilateral activation of neural nets that leads to a
      functional asymmetry of two simulated "cerebral hemispheres" is described. The
      simulation is designed to perform object recognition, while exhibiting
      characteristics typical of human consciousness-specifically, the unitary nature
      of conscious attention, together with a dual awareness corresponding to the
      "nucleus" and "fringe" described by William James (1890). Sensory neural nets
      self-organize on the basis of five sensory features. The system is then taught
      arbitrary symbolic labels for a small number of similar stimuli. Finally, the
      trained network is exposed to nonverbal stimuli for object recognition, leading
      to Gaussian activation of the "sensory" maps-with a peak at the location most
      closely related to the features of the external stimulus. "Verbal" maps are
      activated most strongly at the labeled location that lies closest to the peak on
      homologous sensory maps. On the verbal maps activation is characterized by both
      excitatory and inhibitory Gaussians (a Mexican hat), the parameters of which are
      determined by the relative locations of the verbal labels. Mutual homotopic
      inhibition across the "corpus callosum" then produces functional cerebral
      asymmetries, i.e., complementary activation of homologous "association" and
      "frontal" maps within a common focus of attention-a nucleus in the left
      hemisphere and a fringe in the right hemisphere. An object is recognized as
      corresponding to a known label when the total activation of both hemispheres
      (nucleus plus fringe) is strongest for that label. The functional dualities of
      the cerebral hemispheres are discussed in light of the nucleus/fringe asymmetry.

PMID- 10072695
TI  - Conscious and unconscious processes: the effects of motivation.
AB  - The process-dissociation procedure has been used in a variety of experimental
      contexts to assess the contributions of conscious and unconscious processes to
      task performance. To evaluate whether motivation affects estimates of conscious
      and unconscious processes, participants were given incentives to follow inclusion
      and exclusion instructions in a perception task and a memory task. Relative to a
      control condition in which no performance incentives were given, the results for
      the perception task indicated that incentives increased the participants' ability
      to exclude previously presented information, which in turn both increased the
      estimate of conscious processes and decreased the estimate of unconscious
      processes. However, the results also indicated that incentives did not influence
      estimates of conscious or unconscious processes in the memory task. The findings
      suggest that the process-dissociation procedure is relatively immune to
      influences of motivation when used with a memory task, but that caution should be
      exercised when the process-dissociation is used with a perception task.

PMID- 10072696
TI  - The role of overt rehearsal in enhanced conscious memory for emotional events.
AB  - This study tested the hypothesis that overt rehearsal is sufficient to explain
      enhanced memory associated with emotion by experimentally manipulating rehearsal
      of emotional material. Participants viewed two sets of film clips, one set of
      emotional films and one set of relatively neutral films. One set of films was
      viewed in each of two sessions, with approximately 1 week between the sessions.
      Participants were given a free recall test of all of films viewed approximately 1
      week after the second session. Rehearsal was manipulated by instructing one group
      of participants not to discuss the films with anyone (no talk group) and
      instructing a second group to discuss both sets of films with at least three
      people (forced talk group). A third group consisted of participants instructed
      not to discuss the films with anyone, but who did not comply with these
      instructions (talkers group). All groups recalled significantly more of the
      emotional films than the neutral films. Furthermore, the relative number of
      emotional and neutral films recalled did not differ significantly among the three
      groups. The results indicate that overt rehearsal is insufficient to explain the
      enhancing effects of emotion on memory.

PMID- 10072697
TI  - Calcium alterations in Alzheimer's disease: pathophysiology, models and
      therapeutic opportunities.
AB  - Calcium plays a pivotal role in mediating many important biological functions.
      The intracellular calcium concentration is tightly regulated by a variety of
      systems and mechanisms. Calcium is sequestered by various organelles such as
      mitochondria and/or endoplasmic reticulum and extruded across the plasma membrane
      by energy-dependent transport systems. Different Ca2+-binding proteins are also
      involved in these processes. Alterations in calcium homeostasis might be
      critically implicated in brain aging and in the neuropathology of Alzheimer's
      disease (AD). In fact, one of the postulated mechanisms of beta-amyloid toxicity
      seems to involve a Ca2+ dysregulation accompanied with enhanced vulnerability to
      excitotoxic stimuli. Although brain characteristic lesions-plaques and tangles
      constitute the hallmarks of AD, accumulated evidence suggests the systemic
      feature of this disease. Therefore peripheral cell lines may represent a useful
      approach to explore the cellular pathophysiology of AD, including calcium
      alterations and associated phenomena.

PMID- 10072698
TI  - Effect of bromocriptine on uterine contractility in near-term pregnant rats.
AB  - Treatment of pregnant albino rats at gestation day 9 with the dopamine agonist,
      bromocriptine, in a dose of 0.7 mg kg-1 day-1, i.p. for 11 days produced a
      significant increase in the normal uterine contractions both in vitro and in
      vivo. The increase in frequency (F), amplitude (A) and area under the curve (AUC)
      in the in vitro experiment amounted to 35, 80 and 58%, respectively; while the
      increase in F and A in the in vivo experiment was 36 and 25%, respectively, in
      comparison with the corresponding control group. Addition of oxytocin (5x10(-12)
      4x10(-11) m) to the uterus isolated from rats pretreated with bromocriptine
      resulted in marked uterotonic effect (24, 35 and 49% increase in F; 25, 35 and
      46% increase in A and 42, 62 and 122% increase in AUC of contractions). Also, the
      in vivo experiment showed that an injection of oxytocin at the time of
      investigation (0.125-1.0 I.U. kg-1, i.v.) into rats pretreated with bromocriptine
      caused a marked increase in F (33, 40 and 81%) and A (33, 37 and 75%) of uterine
      contractions compared to the values of bromocriptine-treated animals. These
      results indicate that bromocriptine should be used with caution during pregnancy.
      In addition, this must be considered when using oxytocin during delivery of
      females pretreated with bromocriptine.

PMID- 10072699
TI  - Effects of several drugs on the liver injury induced by delayed-type
      hypersensitivity to picryl chloride by regulating suppressor or helper T cells.
AB  - The effects of histamine, cimetidine, and diphenhydramine on picryl chloride
      (PCl)-induced ear contact sensitivity, as well as liver injury, were examined in
      mice. Histamine was found to produce less response in mice to PCl. In contrast,
      cimetidine, a selective antagonist of histamine type 2 receptor, significantly
      enhanced the response, while diphenhydramine, a selective antagonist of histamine
      type 1 receptor showed no effect. The pre-treatment of 2,4, 6-trinitrobenzene
      sulphonic acid (TNBS) significantly caused a tolerance to the formation of the
      liver injury induced by delayed-type hypersensitivity (DTH) to PCl. Against the
      tolerance, the single intravenous administration of 150 mg kg-1 cyclophosphamide
      (Cy) at 3 days before the TNBS-treatment recovered the response and induced a
      remarkable elevation of serum transaminases. On the other hand, cyclosporin A
      protected the liver injury. These observations revealed that the development of
      acute PCl-DTH liver injury was regulated by the functional state of suppressor
      and helper T cells.

PMID- 10072700
TI  - Eltanolone (5-beta-pregnanolone) does not trigger, and attenuates halothane
      triggering of, malignant hyperthermia in malignant hyperthermia susceptible
      swine.
AB  - Eltanolone is the lipid emulsion formulation, for intravenous use, of the steroid
      anaesthetic 5-beta-pregnanolone. We have screened this agent in malignant
      hyperthermia susceptible (MHS) Landrace swine to assess its potential to trigger
      the Malignant Hyperthermia (MH) syndrome in MHS subjects or to influence
      halothane triggering of MH in such patients. Administered in anaesthetic
      concentration, eltanolone did not trigger the MH syndrome in MHS swine. When co
      administered in low dosage with halothane, the drug prevented initiation of the
      MH syndrome in four of eight pigs and attenuated its progress in the remainder.

PMID- 10072701
TI  - Magnoliae flos inhibits mast cell-dependent immediate-type allergic reactions.
AB  - The mast cell plays a pivotal role in initiating allergic response by secreting
      intracytoplasmic granular mediators such as histamine. Magnoliae flos has been
      used for the treatment of allergic disease in Korea. However, its effect in
      experimental models remains unknown. The present report describes an inhibitory
      effect of Magnoliae flos on mast cell-mediated immediate-type allergic reactions.
      Topical application of compound 48/80 can induce an ear swelling response in
      normal (WBB6F1-+/+) mice but not in the congenic mast cell-deficient WBB6F1-W/Wv
      mice. Magnoliae flos inhibited concentration-dependently mast cell-dependent ear
      swelling response induced by compound 48/80 by topical application. Magnoliae
      flos inhibited concentration-dependently passive cutaneous anaphylaxis induced by
      anti-dinitrophenyl (DNP) IgE in rats by topical application. Magnoliae flos also
      inhibited concentration-dependently the histamine release from the rat peritoneal
      mast cells by compound 48/80 or anti-DNP IgE. Moreover, Magnoliae flos had a
      significant inhibitory effect on compound 48/80-induced systemic anaphylactic
      reaction. These results indicate that Magnoliae flos inhibits immediate-type
      allergic reactions by inhibition of mast cell degranulation in vivo and in vitro.

PMID- 10072702
TI  - Cooling-induced contraction in ovine airways smooth muscle.
AB  - The mechanism of cold-induced bronchoconstriction is poorly understood. This
      prompted the present study whose aim was to determine the step-wise direct effect
      of cooling on smooth muscle of isolated ovine airways and analyse the role of
      calcium in the mechanisms involved. Isolated tracheal strips and bronchial
      segments were suspended in organ baths containing Krebs' solution for isometric
      tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees
      C were examined. Cooling induced a rapid and reproducible contraction
      proportional to cooling temperature in ovine tracheal and bronchial preparations
      which was epithelium-independent. On readjustment to 37 degrees C the tone
      returned rapidly to basal level. Maximum contraction was achieved at a
      temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling
      induced contractions (CIC) was resistant to tetrodotoxin (1; 10 micrometer), and
      not affected by the muscarinic antagonist atropine (1 micrometer) or the alpha
      adrenergic antagonist phentolamine (1 micrometer), or the histamine H1-antagonist
      mepyramine (1 micrometer) or indomethacin (1 micrometer). Ca2+ antagonists
      (nifedipine and verapamil) and Mn2+ raised tracheal but not bronchiolar tone and
      augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min
      had no effect on CIC, although it significantly reduced KCl-induced contraction
      by up to 75%. Cooling inhibited Ca2+ influx measured using 45Ca2+ uptake.
      Caffeine (100 micrometer) significantly inhibited CIC. The results show that
      cooling-induced contractions do not appear to involve activation of nerve
      endings, all surface reception systems or Ca2+ influx. However, CIC is mainly
      dependent on release of intracellular Ca2+.

PMID- 10072703
TI  - Cooling-induced bronchoconstriction: the role of ion-pumps and ion-carrier
      systems.
AB  - The mechanism of cold-induced bronchoconstriction is poorly understood. Our
      previous results show that cooling-induced contractions (CIC) do not involve
      activation of cell surface receptor systems nor innervation nor Ca2+ uptake.
      However, the results show that CIC is mainly dependent on intracellular Ca2+
      [32]. Isolated tracheal strips and bronchiolar segments were suspended in organ
      baths containing Krebs' solution for isometric tension recording. Tissue
      responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling
      ovine tracheal strips and bronchiolar ring segments to 20 degrees C caused a
      rapid contraction which decreased slowly until it reached the basal level in
      approximately 30 min. There is a significant inhibition of 45Ca2+ efflux at 20
      degrees C to those incubated at 37 degrees C. This prompted this study whose aim
      was to determine the role of ion-pump and ion-carrier systems on cooling
      mechanisms. Inhibition of the Na+/K+ pump with ouabain (10 micrometer) evoked
      contraction in tracheal and bronchiolar preparations. When cooling was
      superimposed on this contraction the cooling-induced contractions were reduced in
      the bronchiolar segments. In the tracheal strips, at temperatures down to 15
      degrees C ouabain converted the contractions to a relaxation, but further cooling
      to 10 and 5 degrees C resulted in contractions that were similar to control at 5
      degrees C. Staurosporine, a protein kinase inhibitor (1 micrometer) enhanced CIC
      in trachea and bronchiole. Vanadate, a Ca2+-ATPase pump inhibitor (1 mm)
      potentiated CIC in the two preparations. Trifluoperazine and W-7, calmodulin
      antagonists (10 and 100 micrometer) enhanced CIC in tracheal preparations but not
      in the bronchiolar segments. Thapsigargin and cyclopiazonic acid (CPA),
      inhibitors of sarcoplasmic reticulum (SR) Ca2+-ATPase pump (1 and 10 micrometer)
      potentiated CIC in tracheal but not in bronchiolar preparations. Amiloride,
      Na+/H+ and Na+/Ca2+ exchange system inhibitor (1 mm) abolished CIC in both
      trachea and bronchiole. These results show a strong relationship between cooling
      and the activity of ion transport systems and indicate that CIC is due to
      inhibition of calcium removal mechanisms as a result of inhibition of these ion
      pump and ion carrier systems.

PMID- 10072704
TI  - Anti-inflammatory activity and pharmacokinetic profile of a new parenteral
      formulation of nimesulide.
AB  - Nimesulide, a selective COX-2 inhibitor, exerts potent anti-inflammatory and
      analgesic effects when administered orally, rectally or topically. The present
      study was designed to evaluate the anti-inflammatory activity of a new parenteral
      formulation of nimesulide and to correlate it with the pharmacokinetic profile.
      Nimesulide was administered intramuscularly at increasing doses of 1. 5, 3, 6,
      12.5 and 25 mg kg-1 which produced dose-dependent anti-inflammatory effects in
      the carrageenan-induced rat paw edema. The anti-inflammatory activity of
      nimesulide was greater than that of diclofenac which was administered at
      identical doses though the difference was not statistically significant. Peak
      anti-inflammatory effects with nimesulide were observed between 2 and 3 h post
      treatment which correlates well with the tmax of 115 min. The plasma
      concentration of nimesulide at different time points was assayed using HPLC after
      administration at a dose of 25 mg kg-1. Peak plasma concentration (Cmax) was 23
      microgram ml-1 while t1/2 was derived as 4.2 h. Area Under Curve (AUC(0-6 h)) was
      calculated as 83. 31 microgram ml-1 h-1. No toxicity or adverse effects were
      noted at the doses administered. The present study demonstrates that nimesulide
      administered intramuscularly may be superior to other routes of administration
      when fast onset of action is required with high plasma concentration.

PMID- 10072705
TI  - The effects of excitatory amino acids on isolated gut segments of the rat.
AB  - Glutamate and aspartate are excitatory neurotransmitters in both central and
      peripheral nervous systems, acting on ionotropic and metabotropic receptors. In
      our study we have examined the effects of glutamate, aspartate, N-methyl-d
      aspartate (NMDA), kainic acid and (+/-)-1-aminocyclopentane-cis-1,3-dicarboxylic
      acid (ACPD) on tone and spontaneous activity of isolated rat gastric fundus,
      jejunum, ileum, ascending colon and rectum. Both glutamate and aspartate produced
      concentration-dependent tonic contractions of rat fundus and rectum; the other
      gut segments used in the study were not responsive. While only NMDA and kainic
      acid produced concentration-dependent tonic contractions of isolated rat gastric
      fundus, all three type-selective agonists of glutamate receptors (NMDA, kainic
      acid and ACPD) produced tonic contractions of isolated rat rectum. The results of
      our study suggest that glutamate and aspartate in rat gastric fundus activate
      excitatory intrinsic neurons through only ionotropic receptors (NMDA and non-NMDA
      receptors), while the same action in rat rectum is mediated through both
      ionotropic and metabotropic receptors.

PMID- 10072706
TI  - Bradycardia during citalopram treatment: a case report.
AB  - The authors report the case of a 47-year-old depressive woman treated with
      citalopram 20 mg day-1 for 3 months who presented a marked sinus bradycardia (34
      beats/min) 11 days after the citalopram dose was increased to 40 mg day-1. The
      bradycardia was clinically asymptomatic and disappeared within 24 h after
      citalopram was stopped. Citalopram blood levels were in the usual therapeutic
      range.

PMID- 10072707
TI  - Prevention of ethanol-induced gastric lesions in rats by natural honey and
      glucose-fructose-sucrose-maltose mixture.
AB  - The cytoprotective properties of various natural honey specimens and of a glucose
      fructose-sucrose-maltose mixture (GFSM) against gastric ethanol-induced lesions
      have been evaluated in rats. GFSM mixture and honey (2.5 g kg-1) were given
      orally 30 min before administration of 100% ethanol (5 ml kg-1) for a further 15
      min period. Animal pretreatment with GFSM or honey prevented the formation of
      gastric lesions. The number and severity of haemorrhagic lesions were reduced by
      98%. Stomach acid content increased by 110-703% according to honey specimens. The
      similar protective effects of honey and GFSM mixture suggest that carbohydrates
      at high concentrations behave as mild irritants that can induce adaptive
      cytoprotection.

PMID- 10072710
TI  - Introduction.

PMID- 10072708
TI  - Study of the hypolipidemic properties of pectin, garlic and ginseng in
      hypercholesterolemic rabbits.
AB  - Experimental hypercholesterolemia and its modulation by some natural dietary
      supplements (pectin, garlic and ginseng) and by the drug gemfibrozil were
      studied. Experimental hypercholesterolemia was induced by feeding rabbits a 2%
      cholesterol-enriched diet for 28 days. Hypercholesterolemic rabbits were
      classified into five groups. One group did not receive treatments and served as a
      control hypercholesterolemic group. The other four groups were fed the
      cholesterol-enriched diet in conjunction with either 10% pectin, 2% garlic, 2%
      ginseng or 135 mg g-1 b.w gemfibrozil in a daily oral dose. A normal group of
      rabbits fed a plain chow diet was also included in the study. The hypolipidemic
      effect of the above treatments was examined by estimating serum triglycerides
      (TG), total-, LDL- and HDL-cholesterol. Post-heparin total and hepatic lipase
      activities were estimated in post-heparin plasma obtained 10 min after an
      intravenous injection of heparin (200 IU kg-1 b.w). In order to evaluate the
      antioxidant status of the rabbits, plasma malondialdehyde (MDA) level and
      erythrocyte superoxide dismutase (SOD) activity were measured. After killing,
      aorta from all rabbits were subjected to histopathological examination. Results
      of the study demonstrated that feeding the cholesterol-enriched diet caused a
      significant increase in total-, LDL-, and HDL-cholesterol, plasma MDA and post
      heparin total and hepatic lipase activities. On the other hand, serum TG and
      erythrocyte SOD were not changed. Histopathological examination revealed marked
      alteration in the aortic wall with the appearance of large multiple atheromatous
      plaques. Both garlic and pectin were successful in a significant reduction of the
      hypercholesterolemia in a way comparable to gemfibrozil. Garlic was the only
      treatment that has antilipid peroxidative property. Erythrocyte SOD activity was
      not affected by hypercholesterolemia or by any of the treatments. Also, none of
      the treatments were able to modify the significant elevation of post-heparin
      lipolytic activities associated with the hypercholesterolemia or to significantly
      affect the serum triglycerides level. Finally, among the hypercholesterolemic
      groups that received treatments, the least changes in the aortic wall were shown
      in the animals of the gemfibrozil group. Slight degeneration was observed in the
      aorta of animals treated with pectin or garlic. Ginseng administration failed to
      exert any significant protection from the remarkable hypercholesterolemia or
      atherosclerosis associated with the cholesterol- enriched diet.

PMID- 10072711
TI  - NO: the primary EDRF.
AB  - Since the discovery of an endothelium-derived relaxing factor (EDRF) by Furchgott
      and Zawadzki (Furchgott and Zawadzki. 1980), which was later identified as nitric
      oxide (NO) (Ignarro et al., 1987; Palmer et al., 1987; Furchgott, 1988), it has
      become clear that there are a number of additional endothelium-derived
      vasodilator and vasoconstrictor autacoids (endothelin-1, prostaglandin H2, and
      the endothelium-derived hyperpolarizing factor: EDHF). None of these autacoids
      play such a central role in the regulation of vascular tone and homeostasis as
      the primary EDRF, the free radical NO, which is generated via a live-electron
      oxidation of a guanidino nitrogen from L-arginine by an NO synthase (NOS).

PMID- 10072712
TI  - The alternative: EDHF.
AB  - Endothelium-dependent relaxations cannot be fully explained by the release of
      either NO or/and prostacyclin. Another unidentified substance(s) which
      hyperpolarizes the underlying vascular smooth muscle cells may contribute to
      endothelium-dependent relaxations, especially in small arteries. It has been
      termed endothelium-derived hyperpolarizing factor (EDHF). In blood vessels from
      various species including humans, endothelium-dependent relaxations are partially
      or totally resistant to inhibitors of NO synthase and cyclooxygenase and are
      observed without an increase in the intracellular level of cyclic nucleotides in
      the vascular smooth muscle cells. In some species (canine, porcine and human)
      nitrovasodilators do not cause hyperpolarization while in other (rat, guinea-pig,
      rabbit), they evoke glibenclamide-sensitive hyperpolarization, suggesting the
      involvement of ATP-dependent potassium channels. In contrast, hyperpolarizations
      caused by EDHF are insensitive to glibenclamide but are inhibited by apamin or
      the combination of charybdotoxin plus apamin, indicating that NO and EDHF
      interact with two different targets. The existence of EDHF as a diffusable
      substance has been demonstrated under bioassay conditions whereby the source of
      EDHF was either native vascular segments or cultured endothelial cells. The
      identification of EDHF may allow a better understanding of its physiological and
      pathophysiological role(s).

PMID- 10072713
TI  - Primary endothelial dysfunction: atherosclerosis.
AB  - The endothelium synthesizes and releases several vasodilating factors, including
      nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin. Under
      certain conditions, it also liberates vasocontracting factors. Thus, the
      endothelium plays an important role in regulating vascular homeostasis. Several
      intracellular mechanisms are involved in the synthesis of nitric oxide, including
      receptor-coupled G proteins, the availability of L-arginine, cofactors for
      endothelial nitric oxide synthase and the expression of the enzyme. Endothelial
      dysfunction by aging, menopause and hypercholesterolemia is involved in the
      development of atherosclerotic vascular lesions, and predisposes the blood vessel
      to several vascular disorders, such as vasospasm and thrombosis. Multiple
      mechanisms are apparently involved in the pathogenesis of the endothelial
      dysfunction in atherosclerosis. The reduced production of nitric oxide by the
      endothelium is caused by abnormalities in endothelial signal transduction,
      availability of L-arginine, cofactors for endothelial nitric oxide synthase and
      expression of the enzyme. Other mechanisms may also be involved in the impaired
      endothelium-dependent relaxations in atherosclerosis, including increased
      destruction of nitric oxide by superoxide anion, altered responsiveness of
      vascular smooth muscle, and concomitant release of vasocontracting factors. In
      addition to the treatment of the underlying risk factors, several pharmacological
      agents can improve endothelial dysfunction in atherosclerosis. Thus, the
      endothelium is a novel therapeutic target for the treatment of atherosclerotic
      cardiovascular disease.

PMID- 10072714
TI  - Secondary endothelial dysfunction: hypertension and heart failure.
AB  - The endothelium is a major regulator of vascular tone, releasing vasoactive
      substances such as endothelium-derived nitric oxide (EDRF), endothelium-derived
      hyperpolarizing factor(s), cycloxygenase metabolites, endothelin and other
      endothelium-derived contracting factors (EDCF). In a number of cardiovascular
      pathologies, such as hypertension or heart failure, the balance in the
      endothelial production of vasodilating and vasoconstricting mediators is altered.
      The resulting apparent decrease in endothelium-dependent relaxations is termed
      'endothelial dysfunction'. In hypertensive patients and in animal models of
      hypertension, endothelium-dependent relaxations are impaired. However, this
      endothelial dysfunction presents different characteristics depending on the model
      studied. In Dahl-salt-sensitive rats, the decrease in endothelium-dependent
      relaxations is associated with impaired constitutive nitric oxide synthase
      activity. The presence of an endogenous nitric oxide synthase inhibitor and a
      decreased response of vascular smooth muscle to the mediator may contribute also
      to the dysfunction observed in this model. In other animal models of hypertension
      (such as spontaneous hypertension). the contribution of the L-arginine nitric
      oxide pathway to endothelium-dependent responses appears normal or impaired
      despite reports of increased nitric oxide synthase activity or expression. In
      large arteries from SHR, endothelium-dependent relaxations are impaired mainly
      because of the concomitant augmented release of endoperoxides activating
      thromboxane-endoperoxide receptors. Superoxide anions may also play a role in
      some models, but only in the early phase of the disease: whether or not these
      species contribute to further development of endothelial dysfunction or to
      increases in blood pressure remains to be examined. The endothelial dysfunction
      observed in hypertension is likely to be a consequence of high blood pressure.
      but it could facilitate the maintenance of elevated peripheral resistance at a
      later stage in the disease and favour the occurrence of complications, such as
      atherosclerosis.

PMID- 10072715
TI  - Endothelial dysfunction in human disease.
AB  - The vascular endothelium plays a key role in the local regulation of vascular
      tone by the release of vasodilator substances (i.e. endothelium-derived relaxing
      factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances
      (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like
      acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical
      studies have revealed the importance of EDRF in both basal and stimulated control
      of vascular tone in large epicardial coronary arteries and in the coronary
      microcirculation. The regulatory function of the endothelium is altered by
      cardiovascular risk factors or disorders such as hypercholesterolemia, chronic
      smoking, hypertension or chronic heart failure. Endothelial dysfunction appears
      to have detrimental functional consequences as well as adverse longterm effects,
      including vascular remodelling. Endothelial dysfunction is associated with
      impaired tissue perfusion particularly during stress and paradoxical
      vasoconstriction of large conduit vessels including the coronary arteries. These
      effects may cause or contribute to myocardial ischemia. Several mechanisms may be
      involved in the development of endothelial dysfunction, such as reduced synthesis
      and release of EDRF or enhanced inactivation of EDRF after its release from
      endothelial cells by radicals or oxidized low-density lipoprotein (LDL).
      Increased plasma levels of oxidized LDL have been noted in chronic smokers and
      are related to the extent endothelial dysfunction, raising the possibility that
      chronic smoking potentiates endothelial dysfunction by increasing circulating and
      tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow
      (reflecting reduced shear stress) may be involved in the development of
      endothelial dysfunction and can be reversed by physical training. Other
      mechanisms include an activated renin-angiotensin system (i.e. postmyocardial
      infarction) with increased breakdown of bradykinin by enhanced angiotensin
      converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is
      involved in coronary vasomotor control both in coronary conduit and resistance
      vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent
      mechanism and probably also by blunting the generation of superoxide anion.
      Endothelial dysfunction appears to be reversible by administering L-arginine, the
      precursor of nitric oxide, lowering cholesterol levels, physical training,
      antioxidants such as vitamin C, or ACE inhibition.

PMID- 10072716
TI  - Endothelial dysfunction: from physiology to therapy.
AB  - The endothelium controls the tone of the underlying vascular smooth muscle mainly
      through the production of vasodilator mediators. In some cases, this function is
      hampered by the release of constrictor substances. The endothelial mediators are
      also involved in the regulation by the endothelium of vascular architecture and
      the blood cell-vascular wall interactions. The endothelium-derived factors
      comprise nitric oxide (NO), prostacyclin, and a still unknown endothelium-derived
      hyperpolarizing factor(s) (EDHF). In most vascular diseases, the vasodilator
      function of the endothelium is attenuated. In advanced atherosclerotic lesions,
      endothelium-dependent vasodilatation may even be abolished. Various degrees and
      forms of endothelial dysfunction exist, including (1) the impairment of Galphai
      proteins, (2) less release of NO, prostacyclin and/or EDHF, (3) increased release
      of endoperoxides, (4) increased production of reactive oxygen species, (5)
      increased generation of endothelin-1, and (6) decreased sensitivity of the
      vascular smooth muscle to NO, prostacyclin and/or EDHF. The levels of bradykinin
      and angiotensin II within the vascular wall are controlled by angiotensin
      converting enzyme (ACE). ACE degrades bradykinin and generates angiotensin II.
      Bradykinin stimulates endothelial cells to release vasodilators. The actions of
      the kinin are maintained despite endothelial dysfunction, except in very severe
      arterial lesions. Angiotensin II may be in part responsible for endothelial
      dysfunction because it induces resistance to the vasodilator action of NO. Thus,
      impairment of the generation of angiotensin II blocks the direct and indirect
      vasoconstrictor effect of the peptide. By potentiating bradykinin, ACE inhibitors
      promote the release of relaxing vasodilator mediators to restore vasodilator
      function, and to prevent platelet aggregation as well as the recruitment of
      leukocytes to the vascular wall.

PMID- 10072717
TI  - Expression of cardiac cytokines and inducible form of nitric oxide synthase
      (NOS2) in Trypanosoma cruzi-infected mice.
AB  - Expression of Cardiac Cytokines and Inducible Form of Nitric Oxide Synthase
      (NOS2) in Trypanosoma cruzi-infected Mice. Journal of Molecular and Cellular
      Cardiology (1999) 31, 75-88. Both cardiac cytokine and inducible nitric oxide
      synthase (NOS2) expression have been implicated in the cardiac dysfunction
      associated with myocarditis and cardiomyopathy. Chagas' disease, caused by
      Trypanosoma cruzi, is an important cause of cardiomyopathy. We examined the
      effect of T. cruzi (Brazil strain) infection with or without verapamil treatment
      on the expression of cytokines and NOS2 in the heart. Messenger RNA for NOS2, IL
      1beta, and TNF-alpha was induced in the myocardium of infected mice, and Western
      blot analysis as well as immunohistochemistry demonstrated a significant increase
      in NOS2 protein. Verapamil treatment reduced the expression of cardiac NOS2
      protein and the mRNAs for NOS2, TNF-alpha, and IL-1beta. Infection-associated
      increases in cardiac L-citrulline were also reduced by verapamil treatment.
      Verapamil-treated infected mice that survived for 80 days exhibited less
      inflammation and fibrosis compared to untreated mice. Gated MRI and
      echocardiography revealed an increased right ventricular inner diameter (RVID) in
      untreated but not in verapamil-treated infected CD1 mice. This suggests that the
      infection-associated expression of cytokines and NOS2 in the heart correlate with
      the severity of myocarditis and the effect of verapamil. The RVID was
      significantly increased in infected wild-type (WT) compared to infected syngeneic
      NOS2 knockout (NOS2-/-) mice. Fractional shortening was decreased and myocardial
      L-citrulline was increased in infected WT mice. These data suggest that NO
      generated from cardiac NOS2 may participate in the pathogenesis of murine
      chagasic heart disease.

PMID- 10072718
TI  - Influence of Bretschneider's cardioplegia on norepinephrine release from isolated
      perfused guinea-pig hearts.
AB  - It was the aim of the present study to investigate the influence of
      Bretschneider's cardioplegia on norepinephrine (NE) release [determined by high
      pressure liquid chromatography (HPLC) and electrochemical detection] in isolated
      perfused guinea-pig hearts. The following resulted were noted. (1) Calcium
      dependent exocytotic NE release evoked by electrical field stimulation (12 Hz, 1
      min) was completely suppressed after only 3 min of normothermic (37.5 degrees C)
      Bretschneider's cardioplegia. (2) Stop-flow ischemia is associated with a
      substantial calcium-independent, non-exocytotic NE release, which is regarded as
      a sodium-dependent carrier-mediated process. Accordingly, it is inhibited by
      blockers of the sodium/proton-exchanger (e.g. amiloride) and the neuronal uptake1
      carrier (e.g. desipramine). Compared with stop-flow ischemia alone, cardioplegia
      with 3 min of Bretschneider's histidine-tryptophan-ketoglutarate (HTK)-solution
      preceding stop-flow enhanced NE release at all stop-flow durations (10-90 min)
      investigated (e.g. after 30 min of normothermic Bretschneider's cardioplegia:
      1070+/-41 pmol/g, n = 45, v stop-flow alone: 764+/-48 pmol/g, n = 27, P<0.05).
      The NE concentrations determined in the cardiac effluent upon reperfusion
      followed a typical first order kinetic indicating that the transmitter release
      had already occurred during stop-flow. Hypothermia reduced NE release in a
      temperature-dependent manner down to intramyocardial temperatures of 2 7.5
      degrees C. NE release evoked by Bretschneider's cardioplegia still exceeded that
      induced by stop-flow ischemia alone by up to 60%. The NE release evoked by
      Bretschneider's cardioplegia and stop-flow ischemia was calcium-independent.
      However, it was significantly reduced by desipramine and amiloride, but both
      agents had a more pronounced inhibitory effect on NE release evoked by stop-flow
      ischemia alone. (3) This difference may be due to an intrinsic effect of
      Bretschneider's HTK-solution, as continuous administration of normothermic
      Bretschneider's HTK-solution induced a substantial NE release which was neither
      calcium-dependent nor inhibited by blockade of either uptake1 or sodium/proton
      exchange. It is concluded that Bretschneider's cardioplegia is not
      neuroprotective, as it even augments the stop-flow ischemia-induced nonexocytotic
      NE release.

PMID- 10072719
TI  - Alterations in cardiac membrane beta-adrenoceptors and adenylyl cyclase due to
      hypochlorous acid.
AB  - Although neutrophils and eosinophils are known to produce hypochlorous acid
      (HOCI) at the site of cardiac injury, the exact role of this toxic oxidant on the
      signal transduction mechanism in the heart is not clear. In this study, the
      effects of HOCI on beta-adrenoceptors, G-proteins and adenylyl cyclase activity
      were assessed by incubating rat heart membranes with HOCl. The basal as well as
      forskolin-, NaF-, 5-guanylylimidodiphosphate-, and isoproterenol-stimulated
      adenylyl cyclase activities were depressed by incubating cardiac membranes with
      HOCl. While both the density and affinity of the beta1-adrenoceptors were
      decreased by treatment of cardiac membranes with HOCl, the characteristics of the
      beta2-adrenoceptors were not modified significantly. Although cholera toxin
      stimulated adenylyl cyclase activity, cholera toxin-catalyzed ADP-ribosylation
      and stimulatory guanine nucleotide binding protein immunoreactivity were
      depressed by HOCl, the pertussis toxin-stimulated adenylyl cyclase activity,
      pertussis toxin-catalyzed ADP ribosylation and inhibitory guanine nucleotide
      binding protein immunoreactivity were unaltered by HOCl. The presence of L
      methionine in the incubation medium prevented the HOCl-induced alterations in
      adenylyl cyclase activities and characteristics of beta1-adrenoceptors. These
      results suggest that HOCl may be one of the factors attenuating the beta
      adrenoceptor linked signal transduction mechanism in conditions such as ischemic
      heart disease.

PMID- 10072720
TI  - Improved functional recovery of ischemic rat hearts due to singlet oxygen
      scavengers histidine and carnosine.
AB  - There is increasing evidence that reactive oxygen species (ROS) contribute to
      post-ischemic reperfusion injury, but determination of the specific ROS involved
      has proven elusive. In the present study electron paramagnetic resonance (EPR)
      spectroscopy was used in vitro to measure the relative quenching of singlet
      oxygen (1O2) by histidine and carnosine (beta-alanyl-L-histidine) utilizing the
      hindered secondary amine 2,2,6,6-tetramethyl-4-piperidone HCl (4-oxo-TEMP). The
      relative effect of histidine and carnosine on functional recovery of isolated
      perfused rat hearts was also studied. Functional recovery was measured by left
      ventricular developed pressure (LVDP), first derivative of left ventricular
      pressure (dP/dt), heart rate (HR) and coronary flow (CF). EPR measurements and
      Stern-Volmer plots showed that 400 microM carnosine quenched 1O2 twice as
      effectively as equimolar histidine in vitro. Moreover, 10 mM histidine improved
      functional recovery of isolated rat hearts significantly more than 1 mM
      histidine. Furthermore, 1 mM carnosine improved functional recovery significantly
      more than equimolar histidine and as effectively as 10 mM histidine. Experiments
      with 1 mM mannitol, a known hydroxyl radical scavenger, did not show an
      improvement in functional recovery relative to control hearts, thereby decreasing
      the likelihood that hydroxyl radicals are the major damaging species. On the
      other hand, the correlation between improved functional recovery of isolated rat
      hearts with histidine and carnosine and their relative 1O2 quenching
      effectiveness in vitro provides indirect evidence for 1O2 as ROS participating in
      reperfusion injury.

PMID- 10072721
TI  - Endogenous adenosine reduces the occurrence of ischemia-induced ventricular
      fibrillation in rat heart.
AB  - The aim of this study was to determine whether endogenous adenosine has
      antiarrhythmic effects on ischemia-induced ventricular tachyarrhythmias. We
      therefore modulated the effect of endogenous adenosine in isolated rat hearts
      using four different approaches. First, interstitial adenosine was elevated by
      metabolic inhibition with either EHNA (erythro-9-(2-hydroxy-3-nonly)adenine) or
      acadesine [5-amino-1-beta-D-imidazole-4-carboxamide). Second, cardiac effects of
      A1 adenosine receptors were allosterically enhanced with PD81,723 (2-amino-4,5
      dimethyl-3-thienyl)[3-(trifluoromethyl)phenyl]-methanone . Third, endogenous
      adenosine release was suppressed with NBMPR (S-(4-nitrobenzyl)-6-thioinosine),
      and fourth, adenosine receptor subtypes were blocked with antagonists of
      different selectivity. Regional ischemia, induced by coronary artery ligation,
      caused ventricular fibrillation of a reproducible kind in about 20% of untreated
      hearts with a low calcium concentration in the perfusion medium (0.80 mmol/l
      CaCl2) and in about 75% with high calcium (1.85 mmol/l) within an observation
      period of 30 min. At high calcium, EHNA (1 and 10 micromol/l) and acadesine (500
      micromol/l) suppressed the occurrence of ventricular fibrillation from 68%
      (controls) to 47%, 33% and 38%, respectively. Conversely, PD81,723 (10
      micromol/l) did not influence the occurrence of ventricular fibrillation. At low
      calcium, NBMPR (0.1 and 1 micromol/l) resulted in a concentration-dependent rise
      of ventricular fibrillation from 13% (controls) to 40% and 57%, respectively. The
      adenosine receptor antagonists theophylline (100 micromol/l), XAC (Xanthine Amine
      Congener; 1 micromol/l) and 8-PT (8-phenyltheophylline; 1 micromol/l) caused a
      rise in the occurrence of ventricular fibrillation from 25%, 15% and 18%
      (controls) to 57%, 39% and 44%, respectively, and the selective A2a receptors
      antagonist CSC (8-(3-chlorostyryl)caffeine; 5 micromol/l) from 20% to 56%.
      Conversely, the selective A1 receptor blocker DPCPX (8-cyclopentyl-1,3-dipropyl
      xanthine; 1 micromol/l) was ineffective. NBMPR or EHNA concentration-dependent
      suppressed or increased ischemia-induced adenosine overflow, respectively, in a
      concentration-dependent manner, whereas the adenosine receptor antagonists did
      not influence adenosine overflow. We conclude that endogenous adenosine is an
      antiarrhythmic mediator accumulating in acute ischemic myocardium to a level
      which effectively decreases the occurrence of ventricular fibrillation by an A2
      adenosine receptor activation in the isolated rat heart.

PMID- 10072722
TI  - Heat shock proteins delivered with a virus vector can protect cardiac cells
      against apoptosis as well as against thermal or hypoxic stress.
AB  - Over expression of heat shock proteins (hsps) by transfection of plasmid
      constructs in vitro and in transgenic animals in vivo can protect primary cardiac
      cells from subsequent exposure to severe thermal or hypoxic stress. Here we show
      that such protection can also be achieved by over-expressing the hsps using
      herpes simplex virus (HSV) vectors capable of efficient gene delivery in vivo.
      Moreover, the convenience and high efficiency of this system has allowed us to
      show, for the first time, that over-expression of hsp27 or hsp70 can protect
      cardiac cells against three different apoptosis-inducing stimuli as well as
      against thermal or hypoxic stress whereas hsp56 has no protective effect. The
      potential therapeutic use of inducing the over-expression of specific hsps in
      cardiac cells in vivo using pharmacological or gene therapy procedures is
      discussed.

PMID- 10072723
TI  - Quantification of cardioprotective gene expression in porcine short-term
      hibernating myocardium.
AB  - Several cardioprotective proteins are induced during myocardial ischemia, such as
      heat shock proteins and anti-apoptotic Bcl-2-related proteins which, when
      experimentally overexpressed, have been shown to prevent ischemia-induced myocyte
      loss. As this pathophysiological induction is obviously not sufficient to prevent
      losses of myocytes, we analysed whether it could occur under moderate myocardial
      ischemia with hibernation, thus potentially contributing to myocyte protection
      under these conditions. Therefore, using anesthetized pigs with documented
      myocardial hypoperfusion and short-term hibernation, we investigated the left
      ventricular mRNA expression of the inducible heat shock protein Hsp70 and of the
      anti-apoptotic Bcl-XL in comparison with the pro-apoptotic Bak and Fas
      expression. For transcriptional analyses, the porcine cDNA sequences of Bcl-XL,
      Bak and Fas were identified by polymerase chain reaction (PCR) or by screening of
      a porcine heart cDNA library and cloned. Using reverse transcription polymerase
      chain reaction (RT-PCR), we observed an unchanged mRNA expression of inducible
      Hsp70, Bcl-XL, Bak and Fas after 85 min of hypoperfusion in the short-term
      hibernating myocardium, as well as after 30 min of subsequent reperfusion in the
      stunned myocardium, compared with transcription in a non-hypoperfused control
      area of the same ventricle. In conclusion, the mRNA expression of inducible Hsp70
      and of several apoptosis-modulating proteins is not altered during moderate
      myocardial ischemia resulting in short-term hibernation of the affected area and
      during subsequent stunning.

PMID- 10072724
TI  - Effects of isoproterenol on twitch contraction of wild type and phospholamban
      deficient murine ventricular myocardium.
AB  - Ablation of the gene for phospholamban (PLB), a transmembrane peptide regulator
      for the cardiac sarcoplasmic reticulum Ca2+ pump, in mice brings about a complete
      loss of the myocardial responses to beta-adrenergic agonists (e.g., Luo et al.,
      Circ. Res. 1994; 75: 401). We have evaluated the functional significance of PLB
      independent mechanisms in the myocardial responses to beta-adrenergic stimulation
      in isolated intact ventricular myocardium. We compared the effects of (-)
      isoproterenol (ISO) on isometric twitch contraction of paced right ventricular
      muscle strips of wild type (WT) and PLB-deficient (PLBKO) mice. At 37 degrees C,
      frequent spontaneous contractions in both types of muscles required the inclusion
      of lidocaine, an antiarrhythmic, in the bathing medium. Thus the experiments were
      also performed at two lower temperatures, 30 degrees C and 25 degrees C, at which
      lidocaine was not needed. Under three conditions, in the absence of ISO, PLBKO
      ventricular muscles exhibited substantially shortened time to peak tension (TPT)
      and half relaxation time (TR1/2), compared with the WT muscles. In both WT and
      PLBKO muscles ISO increased the peak developed tension and decreased TPT and
      TR1/2 in a dose-dependent manner although the effects were generally smaller in
      PLBKO than in WT muscles. One micromolar ISO caused TPT and TR1/2 to decrease by
      7.3+/-1.2% (mean+/-SEM) and 7.5+/-1.2% in PLBKO vs. 22.8+/-0.7% and 29.1+/-1.7%
      in WT at 37 degrees C; by 13.5+/-0.4% and 14.1+/-1.2% in PLBKO vs. 31.3+/-0.8%,
      and 44.8+/-1.3% in WT at 30 degrees C; by 15.0+/-2.3% and 21.1+/-4.9% in PLBKO
      vs. 25.8+/-1.9% and 54.0+/-1.9% in WT at 25 degrees C. These findings strongly
      suggest that PLB-independent mechanisms play a significant role in mediating the
      positive inotropic and lusitropic effects of beta-adrenergic agonists on
      ventricular myocardium.

PMID- 10072725
TI  - F1-ATP synthase beta-subunit and cytochrome c transcriptional regulation in right
      ventricular hemodynamic overload and hypertrophically stimulated cardiocytes.
AB  - Cardiac hypertrophic growth secondary to hemodynamic pressure overload causes
      changes in energy requirements that may involve the transcriptional upregulation
      of oxidative phosphorylation genes. Therefore, two representative nuclear-encoded
      genes, the mitochondrial F1-ATP synthase beta-subunit (beta-subunit) and
      cytochrome c (cyt c), were examined in a feline chronic pulmonary artery banded
      right ventricular pressure-overload model. In the hypertrophying right ventricle,
      beta-subunit and cyt c mRNA levels increased after two and seven days, during the
      peak growth response. To examine cardiac transcriptional regulation, neonatal rat
      cardiac myocytes (cardiocytes) were transiently transfected with beta-subunit
      promoter constructs ranging from -1519 nucleotides (nt) upstream of transcription
      initiation as well as cyt c promoter constructs ranging from -726 nt. A full
      length p1519beta-subunit/Luc construct was alpha-adrenergically inducible by 275%
      (+/-30%) with this activation being mapped to an enhancer region between -1519 to
      -1480 nt. Smaller constructs containing more proximal promoter elements were not
      inducible. Additionally, the full-length and enhancer deleted beta-subunit
      constructs were also inducible in electrically stimulated cardiocytes, suggesting
      a different mechanism of activation. Cyt c constructs containing known
      constitutive elements from -191 to -167 nt and -139 to -84 nt were responsible
      for the majority of the reporter activity of the full-length promoter but were
      not inducible in the presence of phenylephrine. Hence, we show that promoter
      regions containing elements common in other metabolism-related gene families are
      active in neonatal rat cardiocytes. Once more, we have identified a beta-subunit
      genomic region responsive to alpha-adrenergic and electrical stimulation.

PMID- 10072726
TI  - Diastolic dysfunction and collagen structure in canine pacing-induced heart
      failure.
AB  - Heart failure is characterized not only by systolic, but also by diastolic
      dysfunction. The present study tested whether or not diastolic dysfunction is
      associated with changes in tissue properties and collagen network structure.
      Heart failure was induced in seven chronically instrumented, conscious dogs by
      rapid left ventricular pacing (2 50 min(-1)). After 2-5 [mean: 4+/-1 (S.D.)]
      weeks pacing, heart failure was apparent from clinical symptoms (ascites,
      cachexia, edema, exercise intolerance) and hemodynamic parameters (significant
      increases of heart rate and left ventricular end-diastolic pressure and decreases
      of left ventricular maximal pressure, dP/dtmax and systolic wall thickening). The
      left ventricle was dilated, as indicated by a decrease of end-diastolic wall
      thickness (6.3+/-2.0 v 7.2+/-2.1 mm; P<0.05; sonomicrometry). The left
      ventricular end-diastolic pressure-strain relation (strain: relative change of
      end-diastolic wall thickness) was obtained during alterations of loading
      conditions by inferior caval vein and descending thoracic aortic occlusion. The
      slope of this relation increased from 85+/-20 to 428+/-188 in heart failure,
      indicating an increase of left ventricular stiffness. Collagen was stained with
      picrosirius red and analyzed using polarized light microscopy. In heart failure,
      the collagen volume fraction remained unchanged (1.9+/-1.2 v 2.3+/-1.3%; N.S.),
      while the nonuniformity of collagen orientation, as reflected by its standard
      deviation, was increased (11.1+/-1.8 v 6.1+/-0.4 o; P<0.05). The nonuniformity of
      collagen fiber orientation correlated with left ventricular stiffness [r=0.75].

PMID- 10072727
TI  - Regional differences in non-enzymatic antioxidants in the heart under control and
      oxidative stress conditions.
AB  - Antioxidants are known to play an important role in mitigating oxidative stress
      injury. Regional concentrations of non-enzymatic antioxidants, redox ratio and
      lipid peroxides were studied in normal, ischemic and ischemic-reperfused rat
      hearts. Isolated perfused rat hearts were made globally ischemic for 45 min and
      reperfused for 15 min. Right ventricular wall (RVW), septum (S) and left
      ventricular wall (LVW) from control, ischemic (I) and reperfused (I-R) hearts
      were analysed. Tocopherol, retinol and ascorbic acid concentrations in different
      regions of perfused control hearts were not different. Reduced glutathione (GSH)
      was significantly lower in the RVW, while S and LVW had about three-fold higher
      levels. Oxidized glutathione (GSSG) was lower in the RVW and most concentrated in
      the LVW. The GSH:GSSG ratio was highest in the septum while RVW and LVW had
      similar values. Lipid hydroperoxide (LPx) concentrations in the three regions of
      control hearts were not different from each other. In I and I-R hearts, vitamin E
      declined in all three regions but the loss was significant only in the septum in
      the I group and in the septum and LVW of the I-R group. Vitamin A showed
      significant loss in all three regions of the I-R group. Vitamin C declined
      significantly only in the RVW of the I-R group. GSH increased in the RVW of the I
      and I-R groups compared to controls. GSSG was increased in the RVW and septum of
      the I group and in all regions of the I-R group. The redox ratio, GSH:GSSG,
      decreased in all regions of both I and I-R groups. LPx were increased in the
      septum of the I group and in all regions of the I-R group. Despite unique
      regional differences in non-enzymatic antioxidants, a comparable increase in LPx
      in the I-R group and similar extent of reduction in the redox ratio in different
      regions of the I and I-R groups, suggest that each myocardial region may use
      different antioxidant mechanisms to withstand oxidative stress.

PMID- 10072728
TI  - High extracellular K+ during hypoxic preconditioning episodes attenuates the post
      ischemic contractile and ionic benefits of preconditioning.
AB  - Hypoxic preconditioning improves contractile recovery and decreases calcium
      loading following ischemia and reperfusion. To test whether changing the trans
      sarcolemmal K+ gradient during the preconditioning period changes
      preconditioning's benefits, isolated rat hearts were subjected to two, 5 min
      hypoxic intervals in the presence of normal K+ (5mM, NmlK-PC) or high K+ (10.3
      mM, HiK-PC), separated by 5 min of normoxic reflow. Preconditioning with 5 mM K+
      significantly improved developed pressure (DP) after 30 min of ischemia as
      compared to non-preconditioned control hearts (55.9+/-4.41% v 12.4+/-2.01% of
      baseline, P<0.05). DP recovery was diminished with 10.3 mM K+ (25.1+/-4.20% of
      baseline, P<0.05). At the end of reperfusion, cell Ca2+ trended lower in hypoxic
      preconditioned hearts compared with control hearts (12.9+/-1.9 v 19.4+/-2.6
      micromol/g dry wt, P=0.09) and was significantly lower than high K+ hearts
      (22.9+/-1.4 micromol/g dry wt, P<0.006). Intracellular K+ during reperfusion was
      significantly higher in preconditioned compared with control hearts (P<0.02) and
      high K+ hearts (P<0.002) (231+/-10 v 166+/-17 v 155+/-14 micromol/g dry wt,
      respectively). Thus, the trans-sarcolemmal K+ gradient during the preconditioning
      period influences preconditioning effects; decreasing the gradient attenuates
      preconditioning's favorable influences on contractile recovery, cellular K+ loss,
      and calcium loading during reperfusion.

PMID- 10072729
TI  - Postnatal development of peptidergic innervation of the canine heart.
AB  - The autonomic innervation of the canine heart develops with considerable regional
      asymmetry during the early neonatal period. To examine the development of the
      peptidergic component of the innervation, 28 mongrel puppies 1-6 weeks of age
      from five litters were studied at weekly intervals. Four of the mothers were also
      studied as adult and breed controls. Tissue neuropeptide Y (NPY) and vasoactive
      intestinal peptide (VIP) concentrations were determined by radioimmunoassay in
      myocardial specimens obtained from several specific sites of the cardiac chambers
      and from the proximal coronary arteries. Data were analysed according to age,
      cardiac chamber/vessel, gender and individual litter. In general, NPY
      concentrations in pg/mg protein were six- to eight-fold higher than those of VIP.
      Also concentrations for both peptides were about two-fold higher in the coronary
      arteries than the myocardium and differed among chambers, being higher and
      similar in the atria and lower in the ventricles, particularly for NPY. No gender
      differences were identified. Concentrations varied among litters, but the
      developmental pattern was similar with the highest peptide concentrations
      identified in the first and fourth week. Whereas the differences among chambers
      may also reflect differing rates of developmental increase of myocardial mass,
      the pattern corresponds only in part to previously identified functional changes
      in sympathetic innervation since, in contrast to previous findings, high NPY
      concentrations in the first 2 weeks suggest anatomically advanced innervation.

PMID- 10072730
TI  - Age-related decrease in cardiac tolerance to oxidative stress.
AB  - Oxygen radical-mediated injury has been implicated in the process of cardiac
      aging. We investigated the tolerance to oxidative stress of hearts from rats of
      different age. Langendorff-perfused hearts from 3-12-month-old rats received a 30
      min infusion of the reactive oxygen specie hydrogen peroxide (H2O2, 60 microM),
      followed by a 15 min wash-out. H2O2 infusion resulted in a significantly larger
      increase in end-diastolic pressure in hearts of 6- and 12-month-old rats than 3
      months (P<0.01). In addition, developed pressure and rate-pressure product
      decreased more evidently in 12-month-old hearts (P<0.01 vs 3 and 6 months).
      Arrhythmia analysis showed higher score in hearts of 12- and 6-month-old rats
      with respect to 3-month-old animals (P<0.05). Cardiac release of oxidized
      glutathione (an index of the ability of the heart to inactivate oxygen
      metabolites) was significantly lower in hearts from rats of 6 and 12 months than
      in younger animals (P<0.001). Finally, cardiac concentrations of the scavenger
      enzymes glutathione peroxidase and Mn-superoxide dismutase also significantly
      decreased with age. In conclusion, in rat heart metabolic and functional
      tolerance toward oxidative stress decreases with age. This phenomenon may
      contribute to the development of cardiovascular alterations with increasing age.

PMID- 10072731
TI  - Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, enhances L
      type Ca2+ current and [Ca2+]i transient in cardiomyocytes.
AB  - This study investigates whether leukemia inhibitory factor (LIF), a potent
      cardiac hypertrophic cytokine, affects the L-type Ca2+ current (I(Ca,L)) and
      intracellular Ca2+ concentrations ([Ca2+]i) in cardiomyocytes. I(Ca,L) was
      recorded using a whole cell patch clamp configuration in guinea pig
      cardiomyocytes, and the [Ca2+]i transient was detected by use of Fluo-3 in rat
      cardiomyocytes. Cells were preincubated with LIF (1000 U/ml) for 15 min before
      whole cell recording. LIF increased I(Ca,L) by 41.8%. LIF synergistically
      increased I(Ca,L) with isoproterenol. Preincubation with H89 did not inhibit the
      LIF-induced increase in I(Ca,L), indicating that this phenomenon is PKA
      independent. PD98059 completely inhibited the increase in I(Ca,L), and this
      effect was dose-dependent (IC50=3.6 micromol/l). Other signal transduction
      inhibitors including AG490, SB203580, chelerythrine, genistein, and KN62 did not
      affect the LIF-induced increase in I(Ca,L). Perforated patch clamp recording
      revealed that LIF maximally increased the I(Ca,L) by 25% at 15 min. LIF also
      increased the peak [Ca2+]i transient level by 63% at 15 min. PD98059 fully
      inhibited the increase in the [Ca2+]i transient. In conclusion, LIF increased
      I(Ca,L) and the [Ca2+]i transient in cardiomyocytes, and the Raf-1/MEK/ERK
      pathway might be involved in the modulation of this activation.

PMID- 10072733
TI  - Tumor necrosis factor-alpha decreases the phosphorylation levels of phospholamban
      and troponin I in spontaneously beating rat neonatal cardiac myocytes.
AB  - The tumor necrosis factor (TNF) alpha level is elevated in patients with advanced
      heart failure, and the phosphorylation of contractile regulatory proteins is
      reduced in the human heart. We hypothesized that TNFalpha affects the
      phosphorylation of proteins involved in regulating contraction; phospholamban
      (PLB), myosin light chain 2 (MLC2) and troponin I (TnI). Spontaneously beating
      rat neonatal cardiac myocytes, prelabelled with [32P]orthophosphate, were treated
      with TNFalpha for 30 min, and stimulated with isoproterenol for 5 min. 32P
      labelled myofibrillar proteins were isolated by 15% SDS-PAGE. Baseline
      phosphorylation levels of PLB, TnI and an unknown 23kDa phosphoprotein were
      decreased by TNFalpha in a dose-dependent manner. Moreover, TNFalpha attenuated
      the phosphorylation levels of PLB and TnI increased by a concentration of 0.01
      microM isoproterenol, but not by 1 microM of isoproterenol. Although TNFalpha had
      no effect on the cAMP content or cAMP-dependent protein kinase activity in the
      presence or absence of isoproterenol, an inverse relationship was observed
      between the concentration of TNFalpha and the cGMP content in cardiac myocytes,
      and treatment with TNFalpha resulted in a concentration-dependent increase in
      type 2A protein phosphatase activity. The observation that TNFalpha decreases
      phosphorylation levels of PLB and TnI in cardiac myocytes suggests that the
      reduction of these protein phosphorylation levels is partially responsible for
      alterations of intracellular Ca2+-cycling and the force of contraction in TNF
      alpha-treated cardiac myocytes. Furthermore, TNFalpha reduces myocyte contraction
      and protein phosphorylation states possibly via cAMP-independent mechanisms, at
      least in part, by the activation of type 2A protein phosphatase.

PMID- 10072732
TI  - Orientation change of cardiocytes induced by cyclic stretch stimulation: time
      dependency and involvement of protein kinases.
AB  - Mechanical stress has been implicated as one of the growth regulators in the
      heart. We investigated the effect of cyclic stretch stimulation on morphology and
      orientation of cultured cardiocytes. Embryonic rat (17 days postcoital)
      cardiomyocytes cultured on silicone dishes were cyclically stretched to 120% in
      length at a frequency of 30 cycles/min. After 12 h, in the initial stage of
      cultivation, cardiocytes and intracellular myofibrils oriented parallel to the
      stretch direction. When the stretch stimulus was prolonged to 24-48 h, myofibrils
      that oriented perpendicular to the stretch direction emerged. Furthermore, when
      the cells were stretched only in the later stage (after 24 h of cultivation),
      both cells and myofibrils tended to orient perpendicular to the stretch
      direction. Next we examined the effects of chemical compounds on these phase
      related changes in myofibril orientation. None of the drugs tested (H-7, HA-1004,
      staurosporine, herbimycin A, genistein, GdCl3, and EGTA) blocked the parallel
      orientation of myofibrils induced by the initial-stage stretch. By contrast, H-7,
      staurosporine, herbimycin A, and genistein did inhibit almost completely the
      perpendicular orientation of the myofibrils induced by the late-stage stretch,
      but HA-1004, GdCl3, or EGTA did not. Immunoblotting study using anti
      phsophotyrosine antibody indicated that tyrosine phosphorylation of a protein of
      about 125 kDa was enhanced in a time-dependent manner by the late-stage stretch,
      but not by the initial-stage stretch. IN CONCLUSION: the alignment change induced
      by cyclic stretch depends on the stage of cultivation: with stretch in the
      initial stage (within 12 h), cells and myofibrils orient parallel to the stretch;
      with stretch in the later stage (after 24 h), they orient perpendicular to the
      stretch. The effect of stretch in the later stage is likely mediated by protein
      kinase C and tyrosine kinase pathways.

PMID- 10072734
TI  - Membrane antioxidant effects of the charged dihydropyridine calcium antagonist
      amlodipine.
AB  - The effect of the highly lipophilic calcium channel antagonist (CCA) amlodipine
      on membrane oxyradical damage was examined and compared to that of other CCA
      analogs and a sulfhydryl-containing ACE inhibitor in isolated membrane vesicles
      enriched with polyunsaturated fatty acids (PUFA). Under physiological-like
      conditions, the dihydropyridine CCA amlodipine significantly (P<0.001) inhibited
      lipid peroxide formation (>10(2) microM) at concentrations as low as 10.0 nM.
      Under identical conditions, inhibition of lipid peroxide formation was not
      observed with representative CCA analogs (felodipine, verapamil, diltiazem) or
      the ACE inhibitor, captopril, at concentrations as high as 1.0 microM. The potent
      antioxidant activity of amlodipine is attributed to distinct membrane physico
      chemical interactions. High-resolution differential scanning calorimetry showed
      that amlodipine effected marked changes in membrane thermodynamic properties as
      compared to other CCA analogs, including a marked reduction in the thermal phase
      transition temperature (-2.6 degrees C), enthalpy (-4.8 J/g) and cooperative unit
      size (-59%), relative to control samples. These findings indicate that the
      chemical structure of amlodipine contributes to distinct membrane biophysical
      interactions that lead to potent lipid antioxidant effects, independent of
      calcium channel modulation. These findings provide insights into potential new
      mechanisms of action for the charged CCA amlodipine.

PMID- 10072735
TI  - Regional expression and functional characterization of the L-type Ca2+-channel in
      myocardium from patients with end-stage heart failure and in non-failing human
      hearts.
AB  - The purpose of the present study was to investigate the expression and functional
      relevance of sarcolemmal L-type Ca2+-channels in failing and non-failing human
      myocardium. The protein expression of sarcolemmal L-type Ca2+-channels was
      determined with 3H-(+)-PN 200-110-binding experiments and Western blot analysis
      using a specific antibody against the alpha1-subunit in membrane preparations of
      ventricular and atrial myocardium from both failing (n = 15) and non-failing
      hearts (n = 8). The gene expression of the ion conducting pore of the L-type Ca2+
      channel was examined with Northern blot technique in human failing and non
      failing RNA. For normalization the RNA expression of calsequestrin was used. In
      electrically driven ventricular papillary muscle strips and auricular trabeculae,
      the responses to nifedipine and Ca2+ as parameters of myocardial function were
      studied. The protein expression as measured by 3H-(+)-PN 200-110-binding (Bmax)
      and Western Blot analysis with calsequestrin as reference was similar in left
      ventricular failing and non-failing myocardium. However, both were reduced in
      atrial compared to ventricular tissue in failing and non-failing hearts. The KD
      remained unchanged. Calsequestrin levels were unaltered in failing and non
      failing hearts. The gene expression of the alpha1-subunit was similar in human
      failing and non-failing hearts. The L-type Ca2+-channel antagonist nifedipine
      reduced force of contraction with the same potency and efficiency in ventricular
      failing and non-failing myocardium. In contrast, the potency of nifedipine was
      higher in atrial than in ventricular tissue. Consistently, atrial myocardium from
      patients with dilated cardiomyopathy was more sensitive towards Ca2+ than those
      of the control group. In conclusion, the altered Ca2+-homeostasis in failing
      human myocardium may be less due to changes in sarcolemmal L-type Ca2+-channel
      expression or function than due to an altered intracellular Ca2+-handling.

PMID- 10072736
TI  - Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose)
      synthetase in isolated working hearts.
AB  - Peroxynitrite and hydroxyl radical are reactive oxidants produced during
      myocardial reperfusion injury. They have been shown to induce dysfunction in
      cardiac myocytes, in part, via the activation of the nuclear enzyme poly (ADP
      ribose) synthetase (PARS). These oxidants can trigger DNA single strand breakage,
      which triggers PARS activation, resulting in cellular NAD+ and ATP depletion and
      cytotoxicity. Recent work has demonstrated that hypoxia-reoxygenation of cardiac
      myocytes in vitro also causes peroxynitrite formation, PARS activation and
      cytotoxicity. In the present study, using hearts from genetically engineered mice
      lacking PARS, we have investigated whether the absence of PARS alters the
      functional response to hypoxia reoxygenation. Isolated work-performing mouse
      hearts were stabilized under the same loading condition (cardiac minute work of
      250 mmHg x ml/min, an afterload of 50 mmHg aortic pressure and similar venous
      return of 5 ml/min, resulting in the same preload). After 30 min equilibration
      the hearts were subjected to 30 min hypoxia followed by 30 min of reoxygenation.
      At the end of the reoxygenation, in hearts from wild-type animals, there was a
      significant suppression in the rate of intraventricular pressure development
      (+dP/dt) from 3523 to 2907 mmHg. There was also a significant suppression in the
      rate of relaxation (-dP/dt) in the wild-type hearts from 3123 to 2168 mmHg. The
      time to peak pressure (TPP) increased from 0.48 to 0.59 ms/mmHg and the half-time
      of relaxation (RT1/2) increased from 0.59 to 0.74 ms/mmHg. In contrast, in the
      hearts from the PARS knockout animals, no significant suppression of +dP/dt (from
      3654 to 3419 mmHg), and no significant increase in the TPP (from 0.462 to 0.448
      ms/mmHg) were found, and the decrease in -dP/dt was partially ameliorated (from
      3399 to 2687 mmHg) as well as the half-time of relaxation (from 0.507 to 0.55
      ms/mmHg) when compared to the response to the wild-type hearts. The current data
      demonstrate that the reoxygenation induced suppression of the myocardial
      contractility is dependent on the functional integrity of PARS.

PMID- 10072737
TI  - Does parental smoking cessation discourage adolescent smoking?
AB  - BACKGROUND: We examined the relationship of smoking cessation in parents to
      smoking and uptake and cessation by their adolescent children. METHODS: We
      analyzed a cross-sectional sample of 4,502 adolescents, ages 15-17 years, who
      lived in two-parent households that were interviewed as part of the 1992-1993
      Tobacco Supplement of the Current Population Survey, which questioned
      householders 15 years of age and older about their smoking history. Ever smokers
      reported smoking at least 100 cigarettes in their lifetime. Former smokers were
      ever smokers who had quit. RESULTS: Multivariate analyses, adjusted for
      demographic characteristics of adolescents, as well as father's age, education,
      and family income, found that adolescents whose parents had quit smoking were
      almost one-third less likely to be ever smokers than those with a parent who
      still smoked. Furthermore, adolescent ever smokers whose parents quit smoking
      were twice as likely to quit as those who had a parent who still smoked. Parental
      quitting is most effective in reducing initiation if it occurs before the child
      reaches 9 years of age. CONCLUSION: Encouraging parents to quit may be an
      effective method for reducing adolescent smoking, through decreased uptake and
      increased cessation. The earlier parents quit, the less likely their children
      will become smokers.

PMID- 10072738
TI  - Page for patients. A message from Preventive Medicine and your physician.

PMID- 10072739
TI  - The effect of physician office visits on CHD risk factor modification as part of
      a worksite cholesterol screening program.
AB  - BACKGROUND: Elevated serum cholesterol is a major risk factor for CHD. Primary
      prevention through behavioral modification has been designated first-line
      treatment for patients with elevated cholesterol. In this study, we assessed the
      impact of a physician office visit after a worksite cholesterol screening on self
      reported changes in diet, weight loss, exercise, and smoking. We hypothesized
      that those individuals who had a physician office visit regarding cholesterol
      would make more changes in CHD risk factors than those who did not have such a
      visit. METHODS: A cohort of 4,928 participants from 33 work-sites in
      Massachusetts and Rhode Island had baseline CHD risk factors evaluated at a
      cholesterol screening and 4,473 were available at follow-up 6 months later by
      telephone interview. A total of 1,957 had elevated cholesterol levels (>/=200
      mg;/dl) and were instructed to visit their physician, in addition to receiving
      educational materials related to CHD risk factor modification. RESULTS: Most
      individuals with elevated cholesterol levels had other prevalent self-reported
      CHD risk factors at baseline: 58% consumed high-fat diets (>30% fat), 43% were
      overweight, 60% had a sedentary lifestyle (sweat-related physical activity <3 x
      per week), and 22% were cigarette smokers. After 6 months of follow-up, 74% of
      participants with high-fat diets reported eating a lower fat diet, 71% of
      overweight participants reported weight loss, 53% of sedentary participants
      attempted to increase physical activity, and 38% of smokers decreased or quit
      cigarette smoking. Thirty-five percent of participants completed the referral for
      a physician office visit to discuss their elevated cholesterol determined at the
      baseline worksite screening. However, these individuals showed only a modest
      change (which was not statistically significant) in self-reported CHD risk
      factors compared with those who did not have follow-up physician visits after
      adjusting for age, sex, race, education, occupation, medical insurance, time
      since last doctor visit, diabetes, and hypertension. Objective measurements of
      serum cholesterol, body mass index, and dietary score were likewise modestly
      improved and not statistically significant. CONCLUSIONS: In 6 months of follow
      up, high absolute levels of CHD risk factor modification were observed after a
      worksite cholesterol screening. A physician office visit added only a modest but
      not statistically significant benefit for further CHD risk factor modification.
      These findings indicate that the follow-up cholesterol-related physician visit
      had little added clinical benefit over the screening intervention alone.

PMID- 10072740
TI  - Promoting cancer screening among the first-degree relatives of breast and
      colorectal cancer patients: the design of two randomized trials.
AB  - BACKGROUND: In this paper two large nationwide trials are described, both of
      which will test a comparable telephone-based counseling intervention to promote
      cancer screening among the first-degree relatives (FDRs) of breast and colorectal
      cancer patients. The unit of randomization will be the family unit of eligible
      FDRs. Access to FDRs will be obtained from their relatives with cancer. Selected
      intervention and design issues are reviewed, including how both projects will
      respond to FDRs who exhibit significant levels of cancer-specific anxiety or
      distress and how potential high-risk cancer families will be accommodated.
      METHODS: Pursuant to the development of both studies, two feasibility surveys
      were conducted to determine whether patients would grant access to their FDRs and
      whether the FDRS identified by these patients would be receptive to the telephone
      intervention. RESULTS: Approximately 80% (106 of 132) of breast cancer patients
      agreed to provide access to their eligible FDRs when contacted on-site at
      participating hospitals and clinics. Of those subsequently selected for telephone
      follow-up (n = 95 or 90%), 80% (n = 76) were successfully contacted by telephone,
      and of these 97% (n = 74) provided the names and telephone numbers of their FDRs.
      Among colorectal cancer patients contacted on-site (n = 46), 96% (n = 44) agreed
      to provide access to their FDRs, and of those contacted by telephone (n = 33 or
      75%), 91% (n = 30) provided the requested information about their FDRs. Once
      contacted, 95% of breast cancer FDRs (55 of 58) and 91% of colorectal cancer
      patients (51 of 56) endorsed the intervention strategy. CONCLUSIONS: It is argued
      that this intervention, if proven effective, could provide an exportable strategy
      for reaching large numbers of high-risk individuals to promote cancer screening.

PMID- 10072741
TI  - Effects of sales promotion on smoking among U.S. ninth graders.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      tobacco marketing efforts and daily cigarette smoking by adolescents. DESIGN:
      This was a longitudinal study of uptake of smoking on a daily basis with smoking
      data from the Monitoring the Future project. Diffusion modeling was used to
      generate expected rates of daily smoking initiation, which were compared with
      actual rates. Study data were from a national survey, administered annually from
      1978 through 1995. Between 4,416 and 6,099 high school seniors participated per
      year, for a total of 94,652. The main outcome measure was a deviation score based
      on expected rates from diffusion modeling vs actual rates of initiation of daily
      use of cigarettes by ninth graders. Annual data on cigarette marketing
      expenditures were reported by the Federal Trade Commission. RESULTS: The
      deviation scores of expected vs actual rates of smoking initiation for ninth
      graders were correlated with annual changes in marketing expenditures. The
      correlation between sales promotion expenditures and the deviation score in daily
      smoking initiation was large (r = 0. 769) and statistically significant (P =
      0.009) in the 1983-1992 period. Correlations between sales promotion and smoking
      initiation were not statistically significant in 1978-1982. Correlations between
      advertising expenditures and smoking initiation were not significant in either
      period. CONCLUSIONS: In years of high promotional expenditures, the rate of daily
      smoking initiation among ninth graders was higher than expected from diffusion
      model predictions. Large promotional pushes by cigarette marketers in the 1980s
      and 1990s appear to be linked with increased levels of daily smoking initiation
      among ninth graders.

PMID- 10072743
TI  - Might stopping smoking reduce injury death risks? A meta-analysis of randomized,
      controlled trials.
AB  - BACKGROUND: Smokers have excesses of injuries. Randomized, controlled trials
      (RCT) could assess whether cigarette smoking (smoking) causes (and smoking
      cessation (cessation) prevents) those injuries. We analyzed injury, accident,
      suicide, and homicide deaths as secondary endpoints in RCT that induced
      cessation. METHODS: RCT were sought via MEDLINE, bibliographies, the CDC Smoking
      and Health database, and the GLOBALink Tobacco listserver. RCT were included if
      (1) net (intervention minus control) cessation totaled over 10% of all
      intervention smokers and (2) injury data were available. Relative risks (RR) were
      summarized by fixed effects modeling. RESULTS: Three trials were located (the
      Lung Health Study, MRFIT, and Whitehall RCT). In-trial annual point prevalence
      cessation averaged 41, 46, and 59% in the intervention group smokers versus 17,
      22, and 28% in the respective controls. Intervention (cessation) was associated
      with pooled injury RR of 0.65 within the trials (95% confidence interval (CI)
      0.36-1.19) and 0.68 (95% CI 0.43-1.09) with additional follow-up in the Lung
      Health and MRFIT populations. CONCLUSIONS: The smoking/injury death association
      is of borderline statistical significance in currently available RCT data. It
      modestly supports the significant forensic, cohort, case-control, cross
      sectional, challenge-rechallenge, in vitro, and animal data suggesting that
      smoking may cause injury. Direct tests of the hypothesis could strengthen this
      inference.

PMID- 10072742
TI  - Changes in the smoking behavior of elderly Mexican Americans in the Southwest
      from 1982-1984 to 1993-1994.
AB  - OBJECTIVES: The aim of this work was to examine changes in the smoking behavior
      of elderly Mexican Americans in the southwestern United States from the early
      1980s to the early 1990s. METHODS: Data from the 1993-1994 Hispanic EPESE study
      (n = 2,809) on persons ages 65 to 74 and 75 to 84 residing in the five
      southwestern states were compared with data from the 1982-1984 Hispanic HANES
      study (n = 753, persons ages 55 to 74), which included a Mexican American sample
      from the same five southwestern states. RESULTS: Rates of current smoking in 1993
      1994 for persons ages 65 to 74 were approximately half the rates for persons of
      the same age a decade earlier. Smoking rates for persons ages 75 to 84 in 1993
      1994 were significantly lower than rates for persons ages 65 to 74 a decade
      earlier. Finally, rates for persons ages 65 to 74 in 1993-1994 were significantly
      lower than those for persons ages 55 to 64 in 1982-1984. CONCLUSIONS: Although
      some of the declines in smoking in recent years represent aging effects
      (including declines due to greater mortality among smokers), the much lower rates
      for same-age people (65 to 74) over the 10-year period are more significant in
      that they represent cohort differences. It appears that the broader public health
      message that is causing the general population to quit smoking is reaching the
      elderly Mexican American population of the Southwest.

PMID- 10072744
TI  - Serum cholesterol trends among members of the Finnish parliament.
AB  - BACKGROUND. Mortality from coronary heart disease in Finland has declined
      remarkably since the early 1970s. Most of the change has apparently been due to
      the active national strategy for reduction of serum cholesterol levels. This
      study was undertaken to estimate to what extent members of the Finnish parliament
      (MPs) have complied with the national recommendations. METHODS: Serum total and
      HDL cholesterol values were measured from MPs of three subsequent parliaments
      elected in 1987, 1991, and 1995. RESULTS: From 1987 to 1995, the Finnish MPs
      showed a reduction of serum total cholesterol that was significant among males (
      5.2;%, P < 0.05) but not among females (-6.4%, NS) and was somewhat smaller than
      the reduction in the general population during 1987 to 1997 (-9.4% among males
      and -8. 3% among females). The male MPs had a 14% rise in HDL cholesterol (P <
      0.01), while among female MPs and in the general population it decreased by 3.1
      to 3.8% (all NS). The cholesterol levels of female MPs were altogether a little
      lower than in the general population. The Finnish MPs tended to have lower total
      cholesterol levels compared with those reported from Hungarian MPs. CONCLUSION:
      The favorable change in the lipid profile of members of the Finnish parliament
      indicates that they have personally been involved in the national change process.
      Follow-up of risk factors in national decision-makers is a useful part of
      comprehensive monitoring of national coronary heart disease prevention activity.

PMID- 10072745
TI  - Aerobic exercise and resting blood pressure among women: a meta-analysis.
AB  - PURPOSE: The aim of this study was to use the meta-analytic approach to examine
      the effects of aerobic exercise on resting systolic and diastolic blood pressure
      among adult women. METHODS: Studies were retrieved from computer searches
      (MEDLINE, Sport Discus, Current Contents) and bibliographies of retrieved
      articles were cross-referenced. Inclusion criteria were as follows: (1)
      randomized trials, (2) aerobic activity as the primary exercise intervention, (3)
      comparative nonexercise control group included, (4) changes in resting systolic
      and/or diastolic blood pressure assessed for women ages 18 and older, and (5)
      studies published in English-language journals between January 1966 and January
      1998. The primary outcomes retrieved in this study were changes in resting
      systolic and diastolic blood pressure calculated as the difference (exercise
      minus control) of the changes (initial minus final) in these mean values.
      RESULTS: Ten studies representing 732 subjects and 36 primary outcomes (19
      systolic, 17 diastolic) met the criteria for inclusion. Overall, an approximate
      2% decrease in resting systolic and 1% decrease in resting diastolic blood
      pressure were observed (systolic,;x +/- SD = -2 +/- 2.6 mm Hg, 95% bootstrap
      confidence interval -3 to -1 mm Hg; diastolic,;x +/- SD = -1 +/- 1.9 mm Hg, 95%
      bootstrap confidence interval -2 to -1 mm Hg). CONCLUSION: Aerobic exercise
      results in small reductions in resting systolic and diastolic blood pressure
      among adult women. However, a need exists for additional, well-designed studies
      on this topic, especially among hypertensive adult women.

PMID- 10072746
TI  - The Next Step Trial: impact of a worksite colorectal cancer screening promotion
      program.
AB  - BACKGROUND: The Next Step Trial was a randomized trial of worksite colorectal
      cancer screening promotion and nutrition interventions for automobile industry
      employees at increased risk of colorectal cancer. Interventions were tested at 28
      worksites with 5,042 employees. This report describes results of the screening
      promotion intervention. METHODS: Worksites randomized to the control group
      received a standard program including rectal examination, fecal occult blood
      testing, and flexible sigmoidoscopy. Intervention worksites received an enhanced
      program (i.e., standard program plus an educational booklet/telephone call).
      Compliance (i.e., completion of all recommended screening examinations) and
      coverage (i.e., completion of at least one screening examination), the primary
      and secondary outcomes, were measured over 2 years. RESULTS: In the 2 years prior
      to baseline, 61% of employees had been screened. After random assignment,
      baseline differences in several employee characteristics and worksite screening
      procedures were detected, including more past history of screening in control
      worksites. After adjusting for differences, we found modest, but higher,
      compliance and coverage in intervention compared with control worksites (odds
      ratio [95% confidence limits] = 1.46 [1.1-2.0] and 1.33 [1.1, 1.6],
      respectively). CONCLUSIONS: Adding a personally tailored behavioral intervention
      to a standard colorectal cancer screening program can promote continued employee
      participation in screening as measured by compliance. Further research is needed
      to assess intervention effects in other populations.

PMID- 10072747
TI  - Nutrition intervention for high-risk auto workers: results of the Next Step
      Trial.
AB  - BACKGROUND: The Next Step Trial tested interventions encouraging prevention and
      early detection practices in automotive-industry employees at increased
      colorectal cancer risk. This article describes results of the nutrition
      intervention promoting low-fat, high-fiber eating patterns. METHODS: Twenty-eight
      worksites (5,042 employees at baseline) were randomized to a 2-year nutrition
      intervention including classes, mailed self-help materials, and personalized
      dietary feedback. Control worksites received no intervention. Nutrition outcomes
      were assessed by mailed food frequency questionnaires (FFQs) Primary nutrition
      outcomes included percentage energy from fat and fiber density (g/1,000 kcal) at
      1 year postrandomization. Secondary outcomes included servings of
      fruits/vegetables and dietary measures at 2 years postrandomization. Analyses
      were adjusted for within worksite correlations and baseline covariates. Fifty
      eight percent of employees returned FFQs. RESULTS: At 1 year, there were modest
      but statistically significant intervention effects for fat (-0.9 %en), fiber
      (+0.5 g/1,000 kcal), and fruits/vegetables (+0.2 servings/day) (all P < 0.007).
      At 2 years, due to significant positive changes in control worksites,
      intervention effects were smaller, significant for fiber only. Intervention
      effects were larger in younger (<50 years), active employees and class attendees.
      CONCLUSION: The nutrition intervention produced significant but modest effects on
      dietary fat and fiber and fruits/vegetables in these high-risk employees. Age and
      dose effects suggest younger employees may be more responsive to this
      intervention.

PMID- 10072748
TI  - Influence factors on the development of obesity in 3-year-old children based on
      the Toyama study.
AB  - BACKGROUND: Obesity in childhood increases the risk of obesity in adulthood.
      Obesity in adulthood is a risk factor for chronic diseases such as hypertension
      and atherosclerosis. Therefore, it is important to eliminate factors influencing
      the development of obesity in children from the viewpoint of preventive medicine.
      The purpose of this study is to elucidate the relationship between obesity and
      lifestyle in 3-year-old children in a case-control study. METHODS: Subjects were
      selected from the Toyama study at health checkups for 3-year-old children which
      are done routinely by local governments in Japan on all children of that age. A
      special questionnaire consisting of items on lifestyle and environmental factors
      of the children and past histories of parents was distributed to the Toyama study
      participants beforehand and was collected at the checkup. Matched-pair
      comparisons were performed between obese children whose body mass index was 18 or
      more (N = 427) and control children (N = 854) matched by sex and birth month.
      Multivariate stepwise conditional logistic regression analysis was also applied
      to assess the influence of confounding factors. RESULTS: The following six
      factors significantly influenced the development of obese 3-year-old children
      using the Mantel-Haenszel method: the mother's job, limited playtime outdoors (1
      hour or less), snacking irregularity, an overweight father (body mass index >/=
      24), an overweight mother (body mass index >/= 24), and overweight at birth
      (birth weight >/= 3,500 g). An overweight mother or father, limited playtime
      outdoors, overweight at birth, and snacking irregularity were significantly
      related to obesity in 3-year-old children after adjusting for confounding factors
      by multivariate stepwise conditional logistic regression analysis. CONCLUSIONS:
      We have suggested several factors influencing the development of obesity in 3
      year-old Japanese children: parental overweight and overweight at birth as host
      factors, physical inactivity and snacking irregularity as behavioral factors, the
      mother's job as an environmental factor.

PMID- 10072749
TI  - The validity of male patients' self-reports regarding prostate cancer screening.
AB  - BACKGROUND: Despite the high rate of prostate cancer screening, the accuracy of
      male patients' self-reports of screening has not been investigated. This study
      assessed the concordance between patients' self-reports of prostate screening and
      the medical record. METHODS: Focus groups were conducted to obtain male patients'
      perceptions of prostate cancer screening and salient terminology. A sample of
      males (n = 276), 40 years of age or older, completed a 15-item questionnaire.
      Patients' self-reports of PSA and DRE screening were then compared with medical
      records. RESULTS: Results showed that patients' self-reports of DRE and PSA were
      discordant with the medical record 32 and 29% of the time, respectively.
      Sensitivity of patients' self-reports for DRE and PSA was 82 and 74%,
      respectively. Specificity of patients' self-reports for DRE and PSA was 56 and
      65%, respectively. One in five patients reported that they were not sure how a
      doctor checks a man's prostate gland. Only 39% of patients knew that the prostate
      gland can be checked by a blood test. CONCLUSIONS: There were significant
      differences between patients' self-reports and the medical record. The results
      should be of concern to primary care practitioners and to those who evaluate the
      efficacy of prostate cancer screening programs.

PMID- 10072750
TI  - Physical activity and incident hypertension in black and white adults: the
      Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND: The epidemiologic observation that physical activity reduces the risk
      for hypertension has only been made for white men who self-reported hypertension.
      This study examined physical activity and clinically determined incident
      hypertension in black and white men and women of the Atherosclerosis Risk in
      Communities (ARIC) Study. METHODS: ARIC is a population-based prospective study
      with four U.S. clinic centers. The present analyses included 7,459 black and
      white adults 45-65 years of age. Hypertension (systolic/diastolic blood pressure
      >/= 140/90 mm Hg) was defined by blood pressure measured by a random-zero device
      or medication use. Physical activity was assessed with the Baecke questionnaire.
      RESULTS: After adjustment for age, baseline blood pressure, ARIC center,
      education, body mass index, waist-hip ratio, parental history of hypertension,
      cigarette smoking, alcohol consumption, and diet, white men in the highest
      quartile of leisure activity (primarily cycling and walking) had a 34% lower odds
      of developing hypertension over 6 years compared to the least active (OR = 0.66,
      95% CI = 0.47-0.94; P for quartile trend = 0.01). Baseline activity was not
      associated with incident hypertension in white women or blacks. CONCLUSIONS:
      Leisure-time physical activity reduces the odds of hypertension in middle-aged
      white men. Additional studies in women and blacks are needed.

PMID- 10072751
TI  - Physical activity patterns in a diverse population of women.
AB  - BACKGROUND: Demographic and psychosocial correlates of activity in domains other
      than recreational activity have not been well characterized and may be
      particularly relevant for health promotion efforts aimed at women. METHODS: Cross
      sectional relationships between recreational, occupational, and
      household/caregiving physical activity and demographic and psychosocial factors
      were assessed with a mail survey in a random sample of 2,636 ethnically diverse
      women members of a large health maintenance organization, ages 20-65. Activity
      was assessed with a modified Baecke questionnaire that uses categorical responses
      regarding frequency of domain-specific activities to create four semicontinuous
      activity indices (sports/exercise, active living, occupational,
      household/caregiving). RESULTS: Multivariable logistic regression analysis showed
      that the likelihood of being in the highest quartile of the sports/exercise and
      active-living indices, compared with the other three quartiles, was decreased
      among older, nonwhite, less well educated, heavier women who had young children
      at home, lacked motivation to exercise, and perceived external obstacles to
      exercise behavior. The odds ratios (ORs) ranged from 0.38, 95% confidence
      interval (CI) 0.33-0.45, associated with low motivation, to 0.95, 95% CI 0.93
      0.98, associated with increasing body mass index. Social support and confidence
      in one's ability to continue to exercise, even when faced with other pressures
      and demands (termed self-efficacy), were associated with increased likelihood of
      high levels of sports/exercise and active living (OR = 2.34, 95% CI 1. 83-2.98
      and OR = 3.96, 95% CI 2.92-5.38, respectively). In contrast, the highest quartile
      of household/caregiving activity was positively associated with increasing age
      (OR = 1.28, 95% CI 1.16-1.42), Hispanic ethnicity (OR = 1.58, 95% CI 0.55-1.01),
      being married (OR = 1.70, 95% CI 1.33-2.18), having young children at home (OR =
      6.99, 95% CI 4.33-11), and greater time constraints as a barrier to exercise (OR
      = 1.55, 95% CI 1.38-1.74) and was negatively associated with employment (OR =
      0.38, 95% CI 0.30-0.47). Increased likelihood of the highest quartile of
      occupational activity was associated with high school education or less (OR =
      2.26, 95% CI 1.74-2.94) and current smoking (OR = 1.66, 95% CI 1.23-2.23), while
      self-efficacy regarding exercise was associated with decreased likelihood (OR =
      0. 77, 95% CI 0.61-0.96). CONCLUSIONS: These findings suggest that demographic
      and psychosocial correlates of physical activity vary by domain and that
      initiatives to promote physical activity in the population need to take these
      differences into account.

PMID- 10072752
TI  - The role of community pharmacists in health education and disease prevention: a
      survey of their interests and needs in relation to cardiovascular disease.
AB  - BACKGROUND: Recently there has been increased interest in broadening the role of
      community pharmacists to include more health education and disease prevention
      activities such as patient counseling for risk management and interventions to
      improve compliance. However, to date, there is little information on interest in
      prevention among community pharmacists or on their current prevention practices.
      METHOD: Data on current health education and disease prevention practices, as
      well as interest in expanding their role in prevention, were collected in a cross
      sectional mail survey of a random representative sample of community pharmacists
      currently practicing in the province of Quebec. RESULTS: Among 597 eligible
      subjects, 455 (76.2%) completed the questionnaire. Few pharmacists practice
      prevention routinely. Independent correlates of engaging in prevention included
      working in a smaller pharmacy (odds ratio (OR) 3. 2 (95% confidence interval 2.0
      5.3)), owning the pharmacy (OR 1.9 (1. 2-3.0)), moderate/high job satisfaction
      (OR 2.1 (1.4-4.3)), and history of prevention activities in the pharmacy (OR 2.2
      (1.4-3.6)). Over 90% of respondents reported that integrating prevention into
      their practices was important. Independent correlates of high perceived
      importance included working as a salaried pharmacist (OR 2. 3 (1.4-3.8)), high
      job satisfaction (OR 4.1 (1.7-9.7)), and currently practicing prevention (OR 2.0
      (1.2-3.2)). The most important perceived barriers to integrating prevention
      included lack of time and lack of skills/instrumentation for practicing
      prevention. CONCLUSIONS: There is considerable interest among community
      pharmacists in expanding their role to include more prevention, but there are
      many barriers to actualizing this role. Further work should focus on ways to
      overcome these barriers because pharmacists are particularly well-situated to
      make an important contribution to prevention.

PMID- 10072754
TI  - Two forms of expression and genomic structure of the human heterogeneous nuclear
      ribonucleoprotein D-like JKTBP gene (HNRPDL).
AB  - The human DNA- and RNA-binding protein JKTBP is a member of a 2xRNA-binding
      domain (RBD)-glycine family of heterogeneous nuclear ribonucleoproteins that are
      involved in mRNA biogenesis. Northern and Western blottings revealed that mRNAs
      of approx. 1.4 and 2.8kb and proteins of approx. 38 and 53kDa were present in HL
      60 cells and various tissues. Cloning and characterization of a previously
      unknown cDNA for the 2.8kb mRNA indicated that the cDNA encodes a 420 amino acid
      JKTBP polypeptide. Isolation and characterization of the genomic DNA showed that
      the gene (HNRPDL) had nine exons and had two separate transcription start sites
      for the two transcripts. The features of the 5' flanking sequences of these sites
      showed that the gene is a housekeeping gene. Fluorescence in situ hybridization
      mapped the gene to 4q13-q21. From its gene organization, the JKTBP seems to be
      most closely related to hnRNP D/AUF1.

PMID- 10072753
TI  - Cloning and characterization of mammalian SMC1 and SMC3 genes and proteins,
      components of the DNA recombination complexes RC-1.
AB  - Members of the evolutionary conserved Structural Maintenance of Chromosomes (SMC)
      protein family are involved in chromosome condensation and gene dosage
      compensation with the SMC2 and SMC4 subtypes, and sister chromatid cohesion with
      the SMC1 and SMC3 subtypes. The bovine recombination protein complex RC-1, which
      catalyzes DNA transfer reactions, contains two heterodimeric SMC polypeptides,
      the genes of which have now been cloned, sequenced, and classified as bovine
      (b)SMC1 and bSMC3. Both proteins display all the characteristic features of the
      SMC family. FISH analysis localized the mouse SMC3 gene to chromosome 19D2-D3.
      Mono- and polyclonal antibodies specific for either subtype detected high levels
      of protein expression in lymphoid tissues, lung, testis and ovary. No change in
      levels of bSMC1 and bSMC3 proteins occurred after X-ray or UV-light irradiation
      of various cell lines or primary cells, and the amounts of individual proteins
      and the heterodimer are roughly constant throughout the cell cycle.
      Immunofluorescence of mouse cells detected the SMC1 protein in foci associated
      with the chromatin. These foci dissolve and the SMC protein dissociates from the
      chromatin during M phase.

PMID- 10072755
TI  - A phagemid vector using the E. coli phage shock promoter facilitates phage
      display of toxic proteins.
AB  - Phage display is a powerful tool with which to adapt the specificity of protease
      inhibitors. To this end, a library of variants of the potato protease inhibitor
      PI2 was introduced in a canonical phagemid vector. Although PI2 is a natural
      trypsin inhibitor, we were unable to select trypsin-binding variants from the
      library. Instead, only mutants carrying deletions or amber stop codons were
      found. Bacteria carrying these mutations had a much faster growth rate than those
      carrying the wt PI2-encoding gene, even when the promoter was repressed. To
      overcome these problems, two new phagemid vectors for g3-mediated phage display
      were constructed. The first vector has a lower plasmid copy number, as compared
      to the canonical vector. Bacteria harboring this new vector are much less
      affected by the presence of the PI2-g3 fusion gene, which appears from a markedly
      reduced growth retardation. A second vector was equipped with the promoter of the
      Escherichia coli psp operon, instead of the lac promoter, to control the PI2-g3
      gene fusion expression. The psp promoter is induced upon helper phage infection.
      A phagemid vector with this promoter controlling a PI2-g3 gene fusion did not
      affect the viability of the host. Furthermore, both new vectors were shown to
      produce phage particles that display the inhibitor protein and were therefore
      considered suitable for phage display. The inhibitor library was introduced in
      both new vectors. Trypsin-binding phages with inhibitory sequences were selected,
      instead of sequences with stop codons or deletions. This demonstrates the
      usefulness of these new vectors for phage display of proteins that affect the
      viability of E. coli.

PMID- 10072756
TI  - Characterization of a species-specific repetitive DNA from a highly endangered
      wild animal, Rhinoceros unicornis, and assessment of genetic polymorphism by
      microsatellite associated sequence amplification (MASA).
AB  - We have cloned and sequenced a 906bp EcoRI repeat DNA fraction from Rhinoceros
      unicornis genome. The contig pSS(R)2 is AT rich with 340 A (37.53%), 187 C
      (20.64%), 173 G (19.09%) and 206 T (22.74%). The sequence contains MALT box, NF
      E1, Poly-A signal, lariat consensus sequences, TATA box, translational initiation
      sequences and several stop codons. Translation of the contig showed seven
      different types of protein motifs, among which, EGF-like domain cysteine pattern
      signatures and Bowman-Birk serine protease inhibitor family signatures were
      prominent. The presence of eukaryotic transcriptional elements, protein
      signatures and analysis of subset sequences in the 5' region from 1 to 165nt
      indicating coding potential (test code value=0.97) suggest possible regulatory
      and/or functional role(s) of these sequences in the rhino genome. Translation of
      the complementary strand from 906 to 706nt and 190 to 2nt showed proteins of more
      than 7kDa rich in non-polar residues. This suggests that pSS(R)2 is either a part
      of, or adjacent to, a functional gene. The contig contains mostly non-consecutive
      simple repeat units from 2 to 17nt with varying frequencies, of which four base
      motifs were found to be predominant. Zoo-blot hybridization revealed that pSS(R)2
      sequences are unique to R. unicornis genome because they do not cross-hybridize,
      even with the genomic DNA of South African black rhino Diceros bicornis. Southern
      blot analysis of R. unicornis genomic DNA with pSS(R)2 and other synthetic oligo
      probes revealed a high level of genetic homogeneity, which was also substantiated
      by microsatellite associated sequence amplification (MASA). Owing to its
      uniqueness, the pSS(R)2 probe has a potential application in the area of
      conservation biology for unequivocal identification of horn or other body tissues
      of R. unicornis. The evolutionary aspect of this repeat fraction in the context
      of comparative genome analysis is discussed.

PMID- 10072757
TI  - Novel endothelin B receptor transcripts with the potential of generating a new
      receptor.
AB  - Using RT-PCR and rapid amplification of 5' cDNA ends (5' RACE), we have cloned
      three previously unrecognized endothelin B receptor (EDNRB) transcripts from a
      human melanoma cell line. Three distinct types of cDNAs (EDNRBDelta1, Delta2 and
      Delta3) were identified. EDNRBDelta1 starts upstream of the published
      transcription start site of hEDNRB without splicing, whereas, EDNRBDelta2 and
      EDNRBDelta3 are alternatively spliced. EDNRBDelta1 and EDNRBDelta2 share the same
      transcription initiation site and are 560bp upstream of the conventional hEDNRB,
      whereas that of EDNRBDelta3 is 939bp upstream from that described for the
      conventional hEDNRB. Interestingly, many transcription factor motifs are
      detectable in the upstream regions of these transcription initiation sites. The
      predicted amino acid sequences reveal that EDNRBDelta1 and EDNRBDelta2 produce
      the same protein as the conventional hEDNRB, but EDNRBDelta3 would give rise to
      additional in-frame 89- or 83-amino-acid residues at the N-terminus. EDNRBDelta3
      generates the same amino acid sequence at the C terminus, but utilizes the
      polyadenylation signal within the open reading frame, resulting in a shorter
      3'UTR. These transcripts are widely expressed in human tissues, but their
      expression patterns vary between different tissues.

PMID- 10072758
TI  - Calcineurin B- and calmodulin-binding preferences identified with phage-displayed
      peptide libraries.
AB  - Calcineurin B (CnB) and calmodulin (CaM) are two structurally similar but
      functionally distinct 'EF-hand' Ca2+-binding proteins. CnB is the regulatory
      subunit of the CaM-stimulated protein phosphatase, calcineurin. CaM is a unique
      multifunctional protein that interacts with and modulates the activity of many
      target proteins. CnB and CaM are both required for the full activation of the
      phosphatase activity of calcineurin and are not interchangeable. The two proteins
      recognize distinct binding sites on calcineurin A subunit (CnA) and perform
      different functions. Phage-displayed peptide libraries (pIII and pVIII libraries)
      were screened with CnB and CaM to isolate peptides that could then be compared to
      determine if there were binding preferences of the two proteins. The Ca2+
      dependent binding of phage-displayed peptides to CnB and CaM is specifically
      blocked by synthetic peptides derived from the CnB-binding domain of CnA and the
      CaM-binding domain of myosin light chain kinase respectively. Both CnB- and CaM
      binding peptides have a high content of tryptophan and leucine, but CnB-binding
      peptides are more hydrophobic than CaM-binding peptides. CnB-binding peptides are
      negatively charged with clusters of hydrophobic residues rich in phenylalanine,
      whereas the CaM-binding peptides are positively charged and often contain an
      Arg/Lys-Trp motif. The binding preferences identified with peptide libraries are
      consistent with the features of the CnB-binding domains of all CnA isoforms and
      the CaM-binding domains of CaM targets.

PMID- 10072759
TI  - A novel A-isoform-like inositol 1,4,5-trisphosphate 3-kinase from chicken
      erythrocytes exhibits alternative splicing and conservation of intron positions
      between vertebrates and invertebrates.
AB  - Based on the partial peptide sequence of inositol 1,4, 5-trisphosphate 3-kinase
      purified with 135 000-fold enrichment from chicken erythrocytes, cDNA-fragments
      were cloned by RT-PCR using degenerate oligonucleotides. Subsequent hybridization
      screening of an embryonic chicken cDNA library and 5'-RACE yielded a cDNA-contig
      of 2418 bp, encoding a 452 amino acid protein. The amino acid sequence shows the
      highest degree of homology with A-isoforms of inositol 1,4,5-trisphosphate 3
      kinase (65% identities), whereas homology towards B and C isoforms was lower (57%
      and 52% amino acid identities respectively). These findings reveal a new tissue
      specific pattern of A-isoform expression, a form which so far has only been found
      in brain and testes. Two overlapping lambda-genomic clones for chicken inositol
      1,4,5-trisphosphate 3-kinase, isolated by hybridization screening, covered 18 499
      bp of genomic sequence. This contig included four exons: three of them were
      present in all cDNA clones, whereas one was only represented in a single cDNA
      clone. In addition, the sequence of the latter differed from the other cDNAs by
      an in-frame deletion of 72 bp within the coding region for the catalytic domain
      of the enzyme. This divergent cDNA suggests the existence of alternative splice
      products, at least in embryonic tissue.A comparison of the position of introns,
      with the respective introns known from the corresponding gene from Caenorhabditis
      elegans, revealed a high degree of conservation of intron positions between
      vertebrates and invertebrates. Functional data for the enzyme suggests that the
      conserved exons represent defined functional protein modules.

PMID- 10072760
TI  - Isolation and characterization of IPP, a novel human gene encoding an actin
      binding, kelch-like protein.
AB  - The kelch family of proteins is defined by a 50 amino-acid repeat that has been
      shown to associate with actin. Here we describe the cloning and initial
      characterization of IPP, a novel human gene that predicts a kelch family protein
      homologous to the mouse Ipp gene, a previously described kelch family member. A
      3kb IPP cDNA clone was isolated from a human placenta library using a probe
      derived from Ipp. Restriction mapping and Southern blot analysis show that IPP
      comprises eight exons spanning more than 47kb of genomic DNA. Fluorescence in
      situ hybridization maps the gene to chromosome 1p32-1p34. Northern blot analysis
      reveals transcripts of 1.4, 2.2, 5. 0, and 7.3kb. The 1.4 and 2.2kb messages are
      found exclusively in testis, while the 5.0 and 7.3kb messages are expressed at
      varying levels in ovary, placenta, small intestine, spleen, testis, and thymus.
      The IPP cDNA clone contains a 1752bp open reading frame that predicts a 584 amino
      acid, 66kDa protein. Sequence analysis indicates an N-terminal POZ protein
      protein interaction domain and a C-terminal kelch repeat domain consisting of six
      tandemly arranged repeats. Cosedimentation assays performed with these domains
      expressed as glutathione S-transferase fusion proteins demonstrate an actin
      binding activity mediated specifically by the kelch repeat domain of IPP.

PMID- 10072761
TI  - Characterisation and mitochondrial localisation of AUH, an AU-specific RNA
      binding enoyl-CoA hydratase.
AB  - AU-rich elements function as instability elements which direct rapid mRNA
      degradation. AUH protein exhibits an AU-specific RNA-binding property and an
      intrinsic enoyl-CoA hydratase activity and may therefore function to link mRNA
      decay to metabolic processes (. Proc. Natl. Acad. Sci. USA 92, 2051-2055). The
      sequence encoding the murine protein, muAUH, was established by cloning, and the
      corresponding polypeptide predicted to have a molecular mass of 37kDa. As shown
      for the human protein, muAUH is expressed in a 32kDa form and there is 94%
      homology between the two species. Recombinant muAUH was shown to be an RNA
      binding enoyl-CoA hydratase. All murine cells studied contained a single AUH
      transcript of approx. 1.7kb and an investigation of tissue-specific expression
      revealed highest levels in kidney, skeletal muscle, heart, liver and spleen. It
      was further determined, using immunoelectron microscopy, that AUH is located in
      the mitochondria of mouse cells.

PMID- 10072762
TI  - Two short sequences have positive effects on the human p27Kip1 gene
      transcription.
AB  - The cyclin-dependent kinase (Cdk) inhibitor p27Kip1 plays an important role in
      the progression from G1 to S phase in the cell cycle. To study the activities of
      its promoter and other regulatory elements, we have cloned and characterized the
      5'-flanking region of the human p27Kip1 gene. This region, about 3kb in length,
      is GC-rich and shares homology with that of the mouse p27Kip1 gene. Transcription
      start points (tsp) determined by the oligo-capping method are mapped in two
      regions, the cluster I (-479 to -403) and cluster II (-280 to -273). The cluster
      I was the primary functional site in transcription initiation. The luciferase
      activities of serial deletion mutants indicated that two short sequences (-581 to
      -557 and -556 to -526) had positive effects on transcription. The gel shift assay
      showed that factors in HeLa nuclear extract bound to these sequences. Sp1 was the
      major binding factor to the sequence of -556 to -526, wheres yet unidentified
      positive factors bound to the sequence of -581 to -557.

PMID- 10072763
TI  - Identification of two hERR2-related novel nuclear receptors utilizing
      bioinformatics and inverse PCR.
AB  - Identification of novel nuclear receptors based on the highly conserved DNA
      binding domain (DBD) has previously depended mainly on low stringency
      hybridization of cDNA libraries and degenerate PCR. Establishment of the
      expressed sequence tag (EST) database in recent years has provided an alternative
      approach for the discovery of novel members of gene families. The rate-limiting
      step is the conversion of ESTs to full-length cDNA. This article describes the
      identification of two novel nuclear receptors (hERRbeta2 and hERRgamma2) related
      to human estrogen-receptor-related receptor 2 (hERR2) by mining the EST database
      and retrieving of full-length cDNA via inverse PCR on subdivided primary cDNA
      library pools. The deduced protein sequences of hERRbeta2 and hERRgamma2 contain
      500 and 458 amino acid (aa) residues respectively. Sequence analysis revealed
      that hERRbeta2 and hERRgamma2 respectively share 95% and 77% overall aa sequence
      identity with hERR2. However, the extra C-terminal domain in hERRbeta2 and extra
      N-terminal domain in hERRgamma2 are not present in the closely related hERR2 or
      mouse ERR2 (mERR2). Extensive sequence verification revealed that hERR2
      previously reported as a human gene is actually a rat gene, whereas hERRbeta2 is
      the true human ortholog of hERR2 and mERR2. Tissue distribution studies showed
      that hERRgamma2 was expressed in a broader panel of tissues at a higher level
      than hERRbeta2. hERRbeta2 was mapped to cytogenetic locus 14q24.3 approximately 
      14q31, a region containing multiple loci involved in genetic diseases, including
      Alzheimer and diabetes. hERRgamma2 was mapped to 1q32. Given the high sequence
      homology between hERRbeta2 and mERR2, the two receptors may have similar
      biological function in vivo.

PMID- 10072764
TI  - The structure of the rat amiloride-sensitive epithelial sodium channel gamma
      subunit gene and functional analysis of its promoter.
AB  - Prolonged dietary Na+ depletion and chronic administration of adrenal steroids
      increase steady-state mRNA levels of the gamma subunit of the epithelial sodium
      channel (gammaENaC) in rat colon. This increase correlates with a marked increase
      in transepithelial Na+ transport and is thought to occur via transcriptional
      regulation. To begin to evaluate these mechanisms in detail, we determined the
      organization of the rat gammaENaC gene. A rat genomic library was screened and
      overlapping lambda clones that together span the gene (approximately 36 kb) and
      contain at least 1 kb of 5' flanking genomic DNA were isolated. As in the human
      gene, the rat gammaENaC gene contains 13 exons and a CpG island at the 5' end of
      the gene. A single transcription start site was identified in rat kidney by
      nuclease protection assay defining a 5' untranslated region of 126 nt. The
      translation initiation codon was identified within the second exon and the entire
      3' UTR (approximately 1 kb) was within the last exon. 800 bp of 5' flanking
      sequence, as well as the 3.4 kb first intron, were sequenced and analyzed for
      transcriptional regulatory motifs. Analogous to the human gammaENaC gene [Thomas,
      C.P., Doggett, N.A., Fisher, R., Stokes J.B., 1996. Genomic organization and the
      5' flanking region of the gamma subunit of the human amiloride-sensitive
      epithelial sodium channel. J. Biol. Chem. 271, 26 062--26 066], two GC boxes were
      seen at -30 and -61 to the transcription start site. In addition, putative AP-1,
      AP-2, CRE, Sp1 and GATA-1 and GRE motifs were identified elsewhere in the 5'
      flanking region or the first intron. Two mammalian-wide interspersed repeats and
      a rodent-specific B1 repeat were also identified within the first intron.
      Fragments containing the putative GRE motifs coupled to luciferase did not confer
      a glucocorticoid-stimulated response in two cell lines that contained a
      functional glucocorticoid receptor. However, a 76 nt rat gammaENaC 5' flanking
      fragment (-76 to +68) directed expression of luciferase in the epithelial cell
      lines H441 and FRTL5, suggesting that this minimal region that contained both GC
      boxes was sufficient for promoter activity.

PMID- 10072765
TI  - DnaA proteins of Escherichia coli and Bacillus subtilis: coordinate actions with
      single-stranded DNA-binding protein and interspecies inhibition during open
      complex formation at the replication origins.
AB  - DnaA-mediated unwinding of the AT-rich region in the replication origins of
      Escherichia coli and Bacillus subtilis was analysed in vitro with and without
      single-stranded DNA-binding protein (SSB). In the presence of SSB, the unwound
      region was larger by a defined number of base pairs. Although the overall
      structure of the origins is very different, the size and structure of the unwound
      region were similar. The unwinding reaction at oriC of one organism was inhibited
      by DnaA protein of the other bacterium. Similarly, hybrid DnaA proteins with
      swapped DNA-binding domains were inactive and inhibitory to 'open complex'
      formation at both origins. We suggest that the inhibition is due to inactive
      mixed complexes.

PMID- 10072766
TI  - Identification of four CCCH zinc finger proteins in Xenopus, including a novel
      vertebrate protein with four zinc fingers and severely restricted expression.
AB  - Tristetraprolin (TTP), the prototype of a class of CCCH zinc finger proteins, is
      a phosphoprotein that is rapidly and transiently induced by growth factors and
      serum in fibroblasts. Recent evidence suggests that a physiological function of
      TTP is to inhibit tumor necrosis factor alpha secretion from macrophages by
      binding to and destabilizing its mRNA (Carballo, E., Lai, W.S., Blackshear, P.J.,
      1998. Science, 281, 1001-1005). To investigate possible functions of CCCH
      proteins in early development of Xenopus, we isolated four Xenopus cDNAs encoding
      members of this class. Based on 49% overall amino acid identity and 84% amino
      acid identity within the double zinc finger domain, one of the Xenopus proteins
      (XC3H-1) appears to be the homologue of TTP. By similar analyses, XC3H-2 and XC3H
      3 are homologues of ERF-1 (cMG1, TIS11B) and ERF-2 (TIS11D). A fourth protein,
      XC3H-4, is a previously unidentified member of the CCCH class of vertebrate zinc
      finger proteins; it contains four Cx8Cx5Cx3H repeats, two of which are YKTEL
      Cx8Cx5Cx3H repeats that are closely related to sequences found in the other CCCH
      proteins. Whereas XC3H-1, XC3H-2, and XC3H-3 were widely expressed in adult
      tissues, XC3H-4 mRNA was not detected in any of the adult tissues studied except
      for the ovary. Its expression appeared to be limited to the ovary, oocyte, egg
      and the early embryonic stages leading up to the mid-blastula transition. Its
      mRNA was highly expressed in oocytes of all ages, and was enriched in the animal
      pole cytosol of mature oocytes. Maternal expression was also seen with the other
      three messages, suggesting the possibility that these proteins are involved in
      regulating mRNA stability in oocyte maturation and/or early embryogenesis.

PMID- 10072767
TI  - Cloning and characterization of a Myxococcus xanthus cytochrome P-450 hydroxylase
      required for biosynthesis of the polyketide antibiotic TA.
AB  - The antibiotic TA, a complex macrocyclic polyketide of Myxococcus xanthus, is
      produced, like many other polyketides, through successive condensations of
      acetate by a type I polyketide synthase (PKS) mechanism. The chemical structure
      of this antibiotic and the mechanism by which it is synthesized indicate the need
      for several post-modification steps, such as a specific hydroxylation at C-20.
      Previous studies have shown that several genes, essential for TA biosynthesis,
      are clustered in a region of at least 36kb, which was subsequently cloned and
      analyzed. In this study, we report the analysis of a DNA fragment, containing a
      specific cytochrome P-450 hydroxylase, presumably responsible for the sole non
      PKS hydroxylation at position C-20. Functional analysis of the cytochrome P-450
      hydroxylase gene through specific gene disruption confirms that it is essential
      for the production of an active TA molecule.

PMID- 10072768
TI  - A TM3-like MADS-box gene from Eucalyptus expressed in both vegetative and
      reproductive tissues.
AB  - MADS-box genes in plants are a diverse class of transcription factors that are
      involved in regulating developmental processes, particularly meristem and organ
      identity during floral development. They are characterized by a highly conserved
      MADS-box domain of 59 amino acids that binds to specific DNA sequences. We report
      the characterization of a cDNA clone, ETL (Eucalyptus TM3 Like), from Eucalyptus
      globulus subspecies bicostata encoding a putative transcription factor of the
      MADS-box class that is strongly expressed in both vegetative and floral tissues,
      suggesting that it regulates processes other than floral development. The clone
      was isolated from a floral bud cDNA library with a probe generated from
      Eucalyptus genomic DNA by PCR using degenerate primers to the MADS-box of the
      floral regulatory gene APETALA 1. The ETL cDNA clone encodes a putative protein
      of 206 amino acids that contains an N-terminal MADS-box and a helical domain of
      approx. 60 amino acids predicted to form a coiled-coil (K-box). These structural
      features are characteristic of plant MADS-box proteins. The MADS-box domain
      contains all the signature residues of a class of MADS-box genes typified by the
      tomato gene TM3 and overall, ETL shows 56% amino acid identity to TM3. Like TM3,
      the ETL gene is expressed in both vegetative and reproductive organs,
      predominantly in root and shoot meristems and organ primordia, as well as in
      developing male and female floral organs.

PMID- 10072769
TI  - Selection of cDNAs encoding putative type II membrane proteins on the cell
      surface from a human full-length cDNA bank.
AB  - We have developed a simple method to test whether a hydrophobic segment near the
      N-terminus of a protein functions as a type II signal anchor (SA) in which the N
      terminus faces the cytoplasm. A cDNA fragment containing the putative SA sequence
      of a target clone was fused in-frame to the 5' end of a cDNA fragment encoding
      the protease domain of urokinase-type plasminogen activator (u-PA). The resulting
      fused gene was expressed in COS7 cells. Fibrinolytic activity on the cell surface
      was measured by placing a fibrin sheet in contact with the transfected COS7 cells
      after removing the medium. When the cDNA fragment encoded a SA, the fibrin sheet
      was lysed by the u-PA expressed on the cell surface. The fibrinolytic activity
      was not detected in the culture medium, suggesting that the u-PA remains on the
      cell surface anchored via the SA in the membrane without being cleaved by signal
      peptidase. This fibrin sheet method was successfully applied to select five novel
      cDNA clones encoding putative type II membrane proteins from a human full-length
      cDNA bank.

PMID- 10072770
TI  - Phenobarbital responsiveness conferred by the 5'-flanking region of the rat
      CYP2B2 gene in transgenic mice.
AB  - Phenobarbital (PB) is a prototype for a class of agents that produce marked
      transcriptional activation of a number of genes, including certain cytochrome P
      450s. We used transgenic mouse approaches and multiple gene reporters to assess
      the functional consequences of specific deletions and site-specific mutations
      within the 2.5kb 5'-flanking region of the rat CYP2B2 gene. Protein-DNA
      interactions at the PBRU domain also were characterized. Using the transgenic
      models, we demonstrate that sequences between -2500 and -1700bp of the CYP2B2
      gene are critical for PB induction; mice with 1700 or 800bp of 5'-flanking CYP2B2
      sequence are not PB responsive. DNA affinity enrichment techniques and
      immunoblotting and electromobility shift assays were used to determine that
      nuclear factor 1 (NF-1) interacts strongly with a site centered at -2200bp in the
      PB responsive unit (PBRU) of CYP2B2. To test the functional contribution of NF-1
      in PB activation, we introduced specific mutations within the PBRU NF-1 element
      and demonstrated that these mutations completely ablate the binding interaction.
      However, transgenic mice incorporating the mutant NF-1 sequence within an
      otherwise wild-type -2500/CYP2B2 transgene maintained full PB responsiveness.
      These results indicate that, despite the avidity of the respective DNA-protein
      interaction within the PBRU in vitro, NF-1 interaction is not an essential factor
      directing PB transcriptional activation in vivo.

PMID- 10072771
TI  - Characterization of a murine gene homologous to the bovine CaCC chloride channel.
AB  - The bovine CaCC protein is a putative Ca2+-dependent Cl- channel of airway
      epithelial cells. Therefore, CaCC proteins could contribute to transepithelial Cl
      transport and accordingly modify the phenotype of cystic fibrosis (CF) patients.
      We have identified a murine EST containing a full-length cDNA coding for a 902
      amino-acid protein highly homologous to bovine CaCC. The murine gene (mCaCC) maps
      to chromosome 3 at the H2-H3 band and is expressed, as indicated by Northern blot
      analysis, in mouse skin and kidney but not in brain, heart, lung or testis. RT
      PCR indicates a low expression in tracheal epithelial cells. Heterologous
      expression of mCaCC in Xenopus oocytes elicits membrane currents that are anion
      selective and inhibited by DIDS and by niflumic acid, a blocker of the endogenous
      chloride current in oocytes. The identification of genes belonging to the CaCC
      family will help to evaluate their role as ion channels or channel regulators and
      their actual contribution to epithelial chloride transport.

PMID- 10072772
TI  - Characterization of the carp myosin heavy chain multigene family.
AB  - We isolated partial coding sequences for 29 carp myosin heavy chain genes
      (MyoHCs) and determined the nucleotide sequences around the region encoding the
      loop 2 of the myosin molecule. The predicted amino acid sequences from the
      isolated genes all showed very high similarity to those of skeletal and cardiac
      muscles from higher vertebrates, but not to those of smooth and non-muscle
      counterparts. Among all clones isolated, carp MyoHC10, MyoHCI-1-3 and MyoHC30
      showed exon-nucleotide sequences identical to those of cDNAs encoding the loop 2
      region of the 10 degrees C-, intermediate- and 30 degrees C-type fast skeletal
      isoforms [Hirayama and Watabe, Euro. J. Biochem. 246 (1997) 380-387]. The loop 2
      of 28 types of carp MyoHCs was encoded by two exons separated by an intron
      corresponding to that of the 16th in higher vertebrate MyoHCs, whilst this intron
      was not found in carp MyoHC30. Although carp MyoHC30 had a gene organization
      different from those of higher vertebrates and other carp MyoHCs, its predicted
      amino acid sequence for loop 2 showed the highest homology to those of higher
      vertebrates among carp MyoHCs. In the 28 carp MyoHCs containing the intron, a
      combination of different nucleotide sequences for the two resulted in 14 distinct
      series for the combined coding sequence. These different nucleotide sequences
      encoded nine distinct amino acid sequences. Phylogenetic analysis for the present
      loop 2 and light meromyosin previously reported for carp MyoHCs [Imai et al., J.
      Exp. Biol. 200 (1997) 27-34] revealed that carp MyoHCs have recently diverged and
      are more closely related to each other than to MyoHCs from other species.

PMID- 10072773
TI  - Identification of ZFR, an ancient and highly conserved murine chromosome
      associated zinc finger protein.
AB  - In a screen for RNA binding proteins expressed during murine spermatogenesis, we
      cloned a novel, ancient zinc finger protein possessing a region common to a small
      class of RNA binding proteins. Zfr (zinc finger RNA binding) encodes a protein of
      1052 amino acids with three widely spaced Cys2His2 zinc fingers. Outside of the
      zinc fingers, ZFR shares a region that is highly conserved between several RNA
      binding proteins containing copies of the double-stranded RNA binding motif. By
      northern blotting, Zfr is expressed at highest levels within the testis, ovary
      and brain. Immunohistochemistry and confocal microscopy were used to show that
      ZFR is highly expressed during meiosis I in males and females and is chromosome
      associated. Zfr is also expressed in Sertoli cells in the testis and granulosa
      cells in the ovary where it is localized to the nucleus. Using fluorescent in
      situ hybridization we mapped Zfr to chromosome 15 region A. ZFR appears to be an
      ancient protein, as apparent homologs exist in invertebrates (D. melanogaster)
      nematodes (C. elegans) and humans (H. sapiens).

PMID- 10072774
TI  - Cloning of a beta integrin subunit cDNA from an embryonic cell line derived from
      the freshwater mollusc, Biomphalaria glabrata.
AB  - A cDNA encoding an integrin subunit was cloned and structurally characterized
      from an embryonic cell line derived from Biomphalaria glabrata, snail
      intermediate host of the human blood fluke Schistosoma mansoni. Cells of the B.
      glabrata embryonic (Bge) snail cell line were initially tested for their
      sensitivity to the integrin-specific tetrapeptide inhibitor Arg-Gly-Asp-Ser
      (RGDS). Washed Bge cells when exposed to 0.5 to 2.0mM of RGDS were significantly
      inhibited in their ability to spread on a glass substrate. Spreading inhibition
      was specific, since a control peptide Arg-Gly-Glu-Ser (RGES) did not have the
      same effect. RT-PCR was performed using previously reported degenerate
      oligonucleotide primers to the ligand binding domain (LBD) of known beta integrin
      subunits and Bge cDNA. A 137 bp fragment was amplified, TA-cloned, sequenced, and
      the na and deduced aa sequences were compared with other beta integrins. Databank
      analysis showed that the 137 bp product shared >/=55.6% aa similarity to other
      beta integrin LBDs. Southern and northern blot analyses using the 137 bp sequence
      as a probe revealed binding to Bge genomic DNA restriction fragments and to an
      approximately 8 kb poly-(A)+RNA transcript, respectively. An exact 5' primer
      synthesized to the 137 bp product and an oligo-d(T) primer then were used to
      amplify from Bge cDNA, a partial beta integrin sequence of 2285 bp that contained
      a 1971 bp ORF. The remaining upstream coding region was obtained using 5' RACE
      methods. The complete ORF, consisting of 2364 bp, encoded a 788 aa sequence with
      shared similarity to other known beta integrins (44.6-61.5%). Sequence and
      structural comparisons, which include a characteristic LBD, a series of three
      homologous cysteine-rich repeats, membrane proximal sequence (LLTFIHD),
      cytoplasmic NPXY motifs, and predicted domain lengths of the molluscan protein,
      clearly identifies it as an integrin homologue. This report represents the first
      cloning of a cDNA putatively encoding an integrin subunit from molluscan cells,
      and establishes the Bge cell line as a model for studying cellular adhesion in
      molluscs at the molecular level.

PMID- 10072775
TI  - Synthesis and secretion of Providencia rettgeri and Escherichia coli
      heterodimeric penicillin amidases in Saccharomyces cerevisiae.
AB  - The Providencia rettgeri and Escherichia coli pac genes encoding heterodimeric
      penicillin G amidases (PAC) were successfully expressed in Saccharomyces
      cerevisiae. Furthermore, these recombinant enzymes are secreted from the yeast
      cell into the medium which is in contrast to bacterial hosts, where the enzymes
      are retained in the periplasm. Contrary to the P. rettgeri PAC-encoding gene, the
      E. coli pac is poorly expressed in yeast. The highest yield of P. rettgeri PAC
      was obtained with a multi-copy plasmid, resulting in of 1500units per liter. This
      yield is higher by an order of magnitude than that obtained in the best
      recombinant bacterial expression system. The recombinant P. rettgeri enzyme is
      only partially and selectively O-glycosylated. Only every sixth or seventh alpha
      subunit is glycosylated, while the beta-subunit is not glycosylated at all. N
      Glycosylation has not been detected.

PMID- 10072776
TI  - Dorsal-B, a splice variant of the Drosophila factor Dorsal, is a novel Rel/NF
      kappaB transcriptional activator.
AB  - The Drosophila transcription factor Dorsal, a member of the Rel/NF-kappaB family
      of proteins, plays a key role in the establishment of dorsoventral polarity in
      the early embryo and is also involved in the immune response. Here, we present
      evidence that the primary transcript of dorsal can be alternatively spliced,
      generating Dorsal-B, a new Rel/NF-kappaB family member. Dorsal and Dorsal-B are
      identical in the N-terminal region, which comprises both a DNA-binding domain and
      a dimerization domain. However, Dorsal-B lacks the nuclear localization signal
      located at the end of the Rel domain of Dorsal and is totally divergent in the C
      terminal portion. Although Dorsal-B by itself is not able to induce the
      expression of a kappaB-controlled Luciferase reporter gene, we demonstrate that
      its C-terminal portion has transactivating properties. Analysis of the dorsal-B
      expression pattern indicates that the splicing is tissue-specific and excludes a
      putative role in early embryogenesis. However, dorsal-B synthesis is enhanced
      upon septic injury, and this challenge induces a nuclear accumulation of the
      protein in fat body cells suggesting that it may be involved in the immune
      response.

PMID- 10072777
TI  - Identification of a Drosophila homologue to vertebrate Crk by interaction with
      MBC.
AB  - The vertebrate adapter protein termed Crk was initially identified from the
      chicken CT10 retrovirus on the basis of its transforming activity (Mayer et al.,
      1988. Nature 332, 272-275). We have identified a Drosophila protein with homology
      to vertebrate Crk, termed dCRK, by interaction with the protein encoded by the
      Drosophila myoblast city (mbc) gene. The dCRK protein has extensive homology to
      the both the Crk-II form of vertebrate Crk and the Crk-related protein CRKL, and
      includes one SH2 domain followed by two SH3 domains. A single protein of approx.
      37kDa is detected in extracts from embryos, and Northern analysis revealed a
      single transcript of 1.3kb. The dCrk mRNA is abundant throughout embryogenesis,
      declines during the larval stages, and reappears during pupation. In addition,
      maternally-provided transcripts have been detected. During embryogenesis, the
      spatial distribution of this transcript is relatively broad and appears to
      include all germ layers. Finally, dCrk is located on the fourth chromosome,
      approximately at cytological position 101F-102A.

PMID- 10072778
TI  - Identification of an attenuating region in the bovine follicle-stimulating
      hormone beta subunit mRNA that decreases its expression in E. coli.
AB  - Follicle-stimulating hormone (FSH) is one of the key regulators of gonadal
      function in mammals. Recombinant DNA expression of this hormone has proved to be
      a difficult task as expression levels are invariably low, irrespective of the
      expression system employed. In the present study, we have attempted to identify
      reasons for this low expression using bacterial expression vectors, and we report
      here the identification of a theoretically predicted hairpin structure in the
      mRNA corresponding to the N-terminal portion of the mature coding portion of
      bFSHbeta cDNA that is responsible for attenuating its expression in E. coli. When
      full-length FSHbeta was expressed using the bacterial expression vector, a very
      low expression was obtained. However, when fragments of FSHbeta with N-terminal
      deletions (amino acids 24-110 and 13-110) were expressed using the same
      expression strategy, a 30- to 40-fold higher expression was observed. This low
      expression of FSHbeta could be attributed to a hairpin structure present in the
      first 12 codons of mature FSHbeta mRNA. Disruption of this structure without
      changing the amino acid sequence resulted in a higher level of expression of
      FSHbeta. The predicted hairpin structure, though away from the transcriptional
      and translational start site, was able to downregulate the expression of FSHbeta
      probably by impeding the movement of ribosomes.

PMID- 10072779
TI  - The pioneer gene, apontic, is required for morphogenesis and function of the
      Drosophila heart.
AB  - In an effort to isolate genes required for heart development and to further our
      understanding of cardiac specification at the molecular level, we screened PlacZ
      enhancer trap lines for expression in the Drosophila heart. One of the lines
      generated in this screen, designated B2-2-15, was particularly interesting
      because of its early pattern of expression in cardiac precursor cells, which is
      dependent on the homeobox gene tinman, a key determinant of heart development in
      Drosophila. We isolated and characterized a gene in the vicinity of B2-2-15 that
      exhibits an identical expression pattern than the reporter gene of the enhancer
      trap. The product of his gene, apontic (apt; see also "Gellon et al., 1997"),
      does not appear to have any homology with known genes. apt mutant embryos show
      distinct abnormalities in heart morphology as early as mid-embryonic stages when
      the heart tube assembles, in that segments of heart cells (those of myocardial
      and pericardial identity) are often missing. Most strikingly, however, apt mutant
      embryos or larvae only develop a much reduced heart rate, perhaps because of
      defects in the assembly of an intact heart tube and/or because of defects in the
      function or physiological control of the myocardial cells, which normally mediate
      heart contractions. These cardiac defects may be the cause of death of these
      mutants during late embryonic or early larval stages.

PMID- 10072780
TI  - Dual role of extramacrochaetae in cell proliferation and cell differentiation
      during wing morphogenesis in Drosophila.
AB  - The Extramacrochaetae (emc) gene encodes a transcription factor with an HLH
      domain without the basic region involved in interaction with DNA present in other
      proteins that have this domain. EMC forms heterodimers with bHLH proteins
      preventing their binding to DNA, acting as a negative regulator. The function of
      emc is required in many developmental processes during the development of
      Drosophila, including wing morphogenesis. Mitotic recombination clones of both
      null and gain-of-function alleles of emc, indicate that during wing
      morphogenesis, emc participates in cell proliferation within the intervein
      regions (vein patterning), as well as in vein differentiation. The study of
      relationships between emc and different genes involved in wing development reveal
      strong genetic interactions with genes of the Ras signalling pathway (torpedo,
      vein, veinlet and Gap), blistered, plexus and net, in both adult wing phenotypes
      and cell behaviour in genetic mosaics. These interactions are also analyzed as
      variations of emc expression patterns in mutant backgrounds for these genes. In
      addition, cell proliferation behaviour of emc mutant cells varies depending on
      the mutant background. The results show that genes of the Ras signalling pathway
      are co-operatively involved in the activity of emc during cell proliferation, and
      later antagonistically during cell differentiation, repressing EMC expression.

PMID- 10072781
TI  - Xenopus axin interacts with glycogen synthase kinase-3 beta and is expressed in
      the anterior midbrain.
AB  - Axin is encoded by the fused locus in mice and is required for normal vertebrate
      axis formation. It has recently been shown that axin associates with APC, beta
      catenin and glycogen synthase kinase-3 (GSK-3) in a complex that appears to
      regulate the level of cytoplasmic beta-catenin. We have identified the Xenopus
      homologue of axin through its interaction with GSK-3b. Xenopus axin (Xaxin) is
      expressed maternally and throughout early development with a low level of
      ubiquitous expression. Xaxin also shows remarkably high expression in the
      anterior mesencephalon adjacent to the forebrain-midbrain boundary.

PMID- 10072782
TI  - Use of the Gal4-UAS technique for targeted gene expression in the zebrafish.
AB  - The most common way to analyze the function of cloned genes in zebrafish is to
      misexpress the gene product or an altered variant of it by mRNA injection.
      However, mRNA injection has several disadvantages. The GAL4-UAS system for
      targeted gene expression allows one to overcome some of these disadvantages. To
      test the GAL4-UAS system in zebrafish, we generated two different kinds of stable
      transgenic lines, carrying activator and effector constructs, respectively. In
      the activator lines the gene for the yeast transcriptional activator GAL4 is
      under the control of a given promoter, while in the effectors the gene of
      interest is fused to the sequence of the DNA-binding motif of GAL4 (UAS). Crosses
      of animals from the activator and effector lines show that effector genes are
      transcribed with the spatial pattern of the activators. This work smoothes the
      way for a novel method of misexpression of gene products in zebrafish in order to
      analyze the function of genes in developmental processes.

PMID- 10072783
TI  - Regulation of chondrocyte differentiation by Cbfa1.
AB  - Cbfa1, a developmentally expressed transcription factor of the runt family, was
      recently shown to be essential for osteoblast differentiation. We have
      investigated the role of Cbfa1 in endochondral bone formation using Cbfa1
      deficient mice. Histology and in situ hybridization with probes for indian
      hedgehog (Ihh), collagen type X and osteopontin performed at E13.5, E14.5 and
      E17.5 demonstrated a lack of hypertrophic chondrocytes in the anlagen of the
      humerus and the phalanges and a delayed onset of hypertrophy in radius/ulna in
      Cbfa1-/- mice. Detailed analysis of Cbfa1 expression using whole mount in situ
      hybridization and a lacZ reporter gene reveled strong expression not only in
      osteoblasts but also in pre-hypertrophic and hypertrophic chondrocytes. Our
      studies identify Cbfa1 as a major positive regulator of chondrocyte
      differentiation.

PMID- 10072784
TI  - The Enhancer of split complex of Drosophila melanogaster harbors three classes of
      Notch responsive genes.
AB  - Many cell fate decisions in higher animals are based on intercellular
      communication governed by the Notch signaling pathway. Developmental signals
      received by the Notch receptor cause Suppressor of Hairless (Su(H)) mediated
      transcription of target genes. In Drosophila, the majority of Notch target genes
      known so far is located in the Enhancer of split complex (E(spl)-C), encoding
      small basic helix-loop-helix (bHLH) proteins that presumably act as
      transcriptional repressors. Here we show that the E(spl)-C contains three
      additional Notch responsive, non-bHLH genes: m4 and ma are structurally related,
      whilst m2 encodes a novel protein. All three genes depend on Su(H) for initiation
      and/or maintenance of transcription. The two other non-bHLH genes within the
      locus, m1 and m6, are unrelated to the Notch pathway: m1 might code for a
      protease inhibitor of the Kazal family, and m6 for a novel peptide.

PMID- 10072785
TI  - Heart specific expression of mouse BMP-10 a novel member of the TGF-beta
      superfamily.
AB  - Here we report the cloning and expression of murine BMP-10, a novel member of the
      TGF-beta superfamily. In the mouse embryo, BMP-10 expression begins at 9.0 d.p.c.
      and is restricted to the developing heart. Initially, BMP-10 expression localizes
      to the trabeculated part of the common ventricular chamber and to the bulbus
      cordis region. After 12.5 d.p.c., additional BMP-10 expression is seen in the
      atrial wall. The data presented here suggest that BMP-10 plays an important role
      in trabeculation of the embryonic heart.

PMID- 10072786
TI  - Expression of growth/differentiation factor 11, a new member of the BMP/TGFbeta
      superfamily during mouse embryogenesis.
AB  - We have cloned and characterized a new member of the bone morphogenetic
      protein/transforming growth factor beta (BMP/TGFbeta) superfamily, growth
      differentiation factor 11 (Gdf11), from rat incisor pulp RNA by reverse
      transcription-polymerase chain reaction using degenerate primers. The mature
      carboxyl-terminal domain encoded by Gdf11 is most closely related to Gdf8, being
      90% identical to the mouse gene. Northern blot analysis revealed Gdf11 is
      expressed in adult dental pulp and brain. In situ hybridization of sections and
      whole-mount embryos demonstrated Gdf11 is first strongly expressed in restricted
      domains at 8.5 days post coitus (dpc) when it is highest in the tail bud. At 10.5
      dpc, it is expressed in the branchial arches, limb bud, tail bud and posterior
      dorsal neural tube. Later, it is expressed in terminally-differentiated
      odontoblasts, the nasal epithelium, retina and specific regions of the brain.

PMID- 10072787
TI  - Elimination of EVE protein by CALI in the short germ band insect Tribolium
      suggests a conserved pair-rule function for even skipped.
AB  - The question of the degree of evolutionary conservation of the pair-rule
      patterning mechanism known from Drosophila is still contentious. We have employed
      chromophore-assisted laser inactivation (CALI) to inactivate the function of the
      pair-rule gene even skipped (eve) in the short germ embryo of the flour beetle
      Tribolium. We show that it is possible to generate pair-rule type phenocopies
      with defects in alternating segments. Interestingly, we find the defects in odd
      numbered segments and not in even numbered ones as in Drosophila. However, this
      apparent discrepancy can be explained if one takes into account that the primary
      action of eve is at the level of parasegments and that different cuticular
      markers are used for defining the segment borders in the two species. In this
      light, we find that eve appears to be required for the formation of the anterior
      borders of the same odd numbered parasegments in both species. We conclude that
      the primary function of eve as a pair rule gene is conserved between the two
      species.

PMID- 10072788
TI  - Molecular cloning and developmental expression of a zebrafish axonal glycoprotein
      similar to TAG-1.
AB  - TAG-1 is a mammalian cell adhesion molecule of the immunoglobulin superfamily
      that is expressed transiently by a subset of neurons and serves as a fertile
      substrate for neurite outgrowth in vitro (Furley, A.H., Morton, S.B., Manalo, D.,
      Karagogeos, S., Dodd, H., Jessell, T.M., 1990 The axonal glycoprotein TAG-1 is an
      immunoglobulin superfamily member with neurite outgrowth promoting activity. Cell
      61, 157-170). In order to examine the in vivo function of this molecule, we have
      cloned a zebrafish tag1-like cDNA and analyzed its expression patterns. tag1 Is
      expressed transiently by specific subsets of neurons when they are projecting
      their axons or when they are migrating. The specific and dynamic pattern of
      expression of zebrafish tag1 is consistent with its proposed role in axon
      guidance and cell migration.

PMID- 10072789
TI  - Chick Barx2b, a marker for myogenic cells also expressed in branchial arches and
      neural structures.
AB  - We have isolated a new chicken gene, cBarx2b, which is related to mBarx2 in
      sequence, although the expression patterns of the two genes are quite different
      from one another. The cBarx2b gene is expressed in craniofacial structures,
      regions of the neural tube, and muscle groups in the limb, neck and cloaca.
      Perturbation of anterior muscle pattern by application of Sonic Hedgehog protein
      results in a posteriorization of cBarx2b expression.

PMID- 10072790
TI  - Expression of the rat homologue of the Drosophila fat tumour suppressor gene.
AB  - We have sequenced and defined the expression during rat embryogenesis of the
      protocadherin fat, the murine homologue of a Drosophila tumour suppressor gene.
      As previously described for human fat, the sequence encodes a large protocadherin
      with 34 cadherin repeats, five epidermal growth factor (EGF)-like repeats
      containing a single laminin A-G domain and a putative transmembrane portion
      followed by a cytoplasmic sequence. This cytoplasmic sequence shows homology to
      the b-catenin binding regions of classical cadherin cytoplasmic tails and also
      ends with a PDZ domain-binding motif. In situ hybridization studies at E15 show
      that fat is predominately expressed in fetal epithelial cell layers and in the
      CNS, although expression is also seen in tongue musculature and condensing
      cartilage. Within the CNS, expression is seen in the germinal regions and in
      areas of developing cortex, and this neural expression pattern is also seen at
      later embryonic (E18) and postnatal stages. No labelling was seen in adult
      tissues except in the CNS, where the remnant of the germinal zones, as well as
      the dentate gyrus, continue to express fat.

PMID- 10072791
TI  - Fjx1, the murine homologue of the Drosophila four-jointed gene, codes for a
      putative secreted protein expressed in restricted domains of the developing and
      adult brain.
AB  - The Drosophila gene four jointed (fj) codes for a secreted or cell surface
      protein important for growth and differentiation of legs and wings and for proper
      development of the eyes. Here we report the cloning of the mouse four-jointed
      gene (fjx1) and its pattern of expression in the brain during embryogenesis and
      in the adult. In the neural plate, fjx1 is expressed in the presumptive forebrain
      and midbrain, and in rhombomere 4, however a small rostral/medial area of the
      forebrain primordium is devoid of expression. Expression of fjx1 in the neural
      tube can be divided into three phases. (1) In the embryonic brain fjx1 is
      expressed in two patches of neuroepithelium: in the midbrain tectum and the
      telencephalic vesicles. (2) In fetal and early postnatal brain fjx1 is expressed
      mainly by the primordia of layered telencephalic structures: cortex (ventricular
      layer and cortical plate), olfactory bulb (subependymal layer and in the mitral
      cell layer). In addition expression is observed in the superior colliculus. (3)
      In the adult, fjx1 is expressed by neurones evenly distributed in the
      telencephalon (isocortex, striatum, hippocampus, olfactory bulb, piriform
      cortex), in the Purkinje cell layer of the cerebellum, and numerous medullary
      nuclei. In the embryo, strong expression can further be seen in the apical
      ectodermal ridge of fore- and hindlimbs and in the ectoderm of the branchial
      arches.

PMID- 10072792
TI  - Spatially and temporally-restricted expression of two T-box genes during
      zebrafish embryogenesis.
AB  - T-box genes are conserved in all animal species. We have identified two members
      of the T-box gene family from the zebrafish, Danio rerio. Zf-tbr1 and zf-tbx3
      share high amino acid identity with human, murine, chick and Xenopus orthologs
      and are expressed in specific regions during zebrafish development.

PMID- 10072793
TI  - Expression of Zkrml2, a homologue of the Krml1/val segmentation gene, during
      embryonic patterning of the zebrafish (Danio rerio).
AB  - We have identified Zkrml2, a novel homologue of the segmentation gene Krml/val in
      zebrafish (Danio rerio). Zkrml2 shows 72% and 92% identity in its basic leucine
      zipper domain with mouse Krml1 and zebrafish val, respectively. Zkrml2 is
      expressed coincident with MyoD throughout the somites starting at the three
      somite stage, becomes restricted to the dermomyotome, and subsequently
      disappears. Transient expression is also detected in the reticulospinal and
      oculomotor neurons. Zkrml2 maps to the Oregon linkage group 11 (Boston Linkage
      group 14) with no mapped zebrafish mutations nearby.

PMID- 10072794
TI  - [Immunological features of steroid-resistant asthma].
AB  - OBJECTIVE: To investigate the pathogenesis and treatment of steroid-resistant
      (SR) asthma. METHODS: Changes of serum levels of soluble interleukin-2 receptor
      (sIL-2R) after oral prednisone (20 mg/d) therapy were observed, and the
      peripheral blood T cell inhibitory effects of dexamethasone, oxymatrine and
      thymus-derived immunoinhibiting agents were studied in vitro by lymphocyte
      proliferation assay. RESULTS: After prednisone therapy, serum levels of sIL-2R
      were significantly decreased in steroid-sensitive (SS) asthmatics (P < 0.001) but
      not in SR asthmatics (P > 0.5). The inhibitory effects of dexamethasone (10(-7)
      mol/L) on the proliferation of T cells from SR asthmatics were significantly less
      than those from SS asthmatics (P < 0.002). Oxymatrine and thymus-derived immuno
      inhibiting agents inhibited T cell proliferation to a similar degree between SR
      and SS asthmatics. CONCLUSIONS: Persistent T cell activation due to relative
      unresponsiveness of T cells to glucocorticoids was a feature of SR asthma. The
      therapeutic benefit of immuno-inhibiting agents other than glucocorticoids in the
      management of SR asthma deserves further investigation.

PMID- 10072795
TI  - [Changes of K+ channel behaviors in airway smooth muscle from asthmatic guinea
      pigs].
AB  - OBJECTIVE: To observe asthma-induced changes of single K+ channel behaviors in
      acutely dissociated airway smooth muscle of guinea-pig. METHODS: The resting
      membrane potential (MP) was measured in whole-cell recording configuration. The
      elementary currents flowing through single K+ channel were recorded in cell
      attached patches. RESULTS: The properties in asthmatic group were as follows: (1)
      MP was decreased from -70.3 +/- 3.5 mV to -62.8 +/- 5.6 mV. (2) In the same
      depolarization conditions, the amplitudes of currents decayed and conductant
      values were decreased with significantly difference (about 51%) from the values
      obtained from the control group. (3) Open time constants of fast- and slow-open
      states shortened markedly to 25% and 7% of controls respectively. Shut time
      constants were prolonged. (4) Open probability showed voltage-dependence and was
      decreased in the same voltage range. CONCLUSIONS: Asthmic airway hyperreactivity
      related kinetic properties of K+ channel deficits, which may result a reduced
      threshold of excitation.

PMID- 10072796
TI  - [Changes of plasma endothelium-derived relaxing factor and endothelin-1 in
      patients with chronic cor pulmonale at exercise test].
AB  - OBJECTIVE: The authers investigated the levels of plasma EDRF-nitric oxide (NO)
      and ET-1 in 10 cases of cor pulmonale at exercise. METHODS: Using the
      technologies of cardiac catheter, radioimmunization and biochemical analysis.
      RESULTS: The level of plasma NO was lower in group A (mean pulmonary artery
      pressure (mPAP) < 2.67 kPa) than in group B (mPAP > or = 2.67 kPa) at rest; the
      content of plasma NO increased more markedly in group A than in group B during
      exercise; there was no change in the content of ET-1 in both groups; mPAP
      strongly correlated with plasma NO or ET-1 in both groups. CONCLUSIONS: The
      patients with cor pulmonale at early stage may be in a state of compensated
      release of NO, but its release reserve has been reduced.

PMID- 10072797
TI  - [Expression of FGF-b and C-myc in rats lung tissue affected by hypoxia].
AB  - OBJECTIVE: To study FGF's roles in the reconstruction of vascular walls owing to
      chronic hypoxia. METHOD: 40 SD rats [corrected] were divided into different
      hypoxia groups and proceeded with various hypoxic intervals. Expression of FGF-b
      and transcription of c-myc mRNA of the rats [corrected] lung tissues were
      detected by immunohistochemical method and in situ hybridization. RESULTS: FGF-b
      increased obviously in the smooth muscle and advential tissue of pulmonary
      arteries after 14 days of hypoxia, whereas C-myc mRNA showed overexpression in
      rats [corrected] lung tissue from 7th to 21st day of hypoxia. CONCLUSION: (1)
      Hypoxia may lead to activation of C-myc oncogene and increase of FGF-b expression
      in lung tissue. (2) FGF-b and C-myc oncogene takes part in reconstruction of
      pulmonary arterial wall affected by chronic hypoxia.

PMID- 10072798
TI  - [Effects of hypoxia and taurine on vasoconstriction peptides from cultured bovine
      pulmonary arterial endothelial cells].
AB  - OBJECTIVE: To study roles of endothein-1 (ET-1), angiotensin-II (AT-II) and
      endogenous digitalis-like factor (EDF) from cultured bovine pulmonary arterial
      endothelial cells (PAEC) in the pathogenesis of hypoxic pulmonary hypertension,
      and to evaluate whether Taurine is capable of protecting tissue cells from
      injury. METHODS: Culture of bovine pulmonary arterial endothelial cells and dot
      blot hybridization. RESULTS: PAEC cultured under hypoxia resulted in an increase
      in ET-1 mRNA expression. PAEC cultured under hypoxia induced increase in ET-1, AT
      II and EDF release. By adding taurine to the culture medium, ET-1 mRNA express
      was inhibited. ET-1, AT-II and EDF release were inhibited. CONCLUSIONS:
      Expression of ET-1 mRNA and release of ET-1, AT-II and EDF from PAEC increased
      under hypoxia. Taurine can inhibit the hypoxia-induced expression of ET-1 mRNA of
      PAEC and reduce the release of ET-1, AT-II and EDF from PAEC.

PMID- 10072799
TI  - [Relationship of mdr1 gene expression and multidrug resistance of primary lung
      cancer].
AB  - OBJECTIVE: To evaluate the expression of mdr1 gene in various type of primary
      lung cancer. METHOD: A serious of 48 resected primary lung cancer tissues from 5
      post-chemotherapy and 43 untreated patients and 33 adjacent normal lung tissues
      were analyzed for mdr1 gene by RT-PCR method. RESULTS: Fifteen of 48 tumor
      tissues were found to have overexpression of mdr1 gene, comprising 6 of 12
      adenocarcinomas, 7 of 22 squamous cell carcinomas, 1 of 2 sarcocarcinomas, 1 of
      12 small cell carcinomas. Of 5 post-chemotherapy specimens, only one case showed
      positive. In addition, 3 of 33 adjacent normal tissues also showed mdr1-positive.
      Overexpression of mdr1 gene did not be associated with tumor size, metastasis and
      stage of lung cancer. The relapse rate with mdr1-positive cases was higher (80%)
      than that with mdr1-negative (58%) by one year follow-up of these patients.
      CONCLUSION: Overexpression of mdr1 gene can be detected in untreated primary lung
      cancer, specially in non-small cell lung cancer and may be regarded as one poorly
      prognostic marker.

PMID- 10072800
TI  - [Clinical and pathological analysis of liver injury resulting from rifampin and
      isoniazid].
AB  - OBJECTIVE: To explore the relationship between clinical manifestations and
      pathological changes of liver injury resulting from rifampin and isoniazid.
      METHOD: 194 cases treated with rifampin and isoniazid, among them liver biopsies
      were done once in 28 cases, twice in 17 cases, were observed. RESULTS: 21 of 59
      cases with positive HBVM and 13 out of 135 cases with negative HBVM showed
      abnormal liver function after treatment, and the elevation of ALT was in
      accordance with the degree of liver pathological injury. Elevated ALT and liver
      pathological injury returned to normal within 6 weeks after rifampin and
      isoniazid were stopped or reduced in doses. No significant difference was found
      between chronic hepatis B and rifampin, isoniazid in causing liver pathological
      injury, but two different points were noted in their manifestations: 1. The cells
      mainly caused portal inflammation were lymphocytes in the former, while
      eosinophils in the latter. 2. The incidence of intrahepatic cholestasis was
      higher in the latter. CONCLUSION: The incidence of liver injury in HBVM positive
      group is higher than that in HBVM negative group because liver injury exists in
      the former before treatment, and the mechanisms causing liver injury may be
      different.

PMID- 10072801
TI  - [Construction of mycobacterium tuberculosis genomic library].
AB  - OBJECTIVE: To provide effective tools for identification and characterization of
      M. tuberculosis genes/antigenes and to evaluate their roles in diagnosis,
      vaccination, drug resistance, and pathogenesis. METHODS: M. tuberculosis genomic
      DNA obtained from H 37 Ra strain was partially digested with DNase I. The DNA
      fragments ranging from 4-8 kb were isolated from agarose gel and ligated to EcoR
      I adaptor, and the products were linked to lamda gt11 arms and packaged using an
      in vitro packaging extract. The different diluted bacteriophages were used to
      transfect bacteria Y1090. RESULTS: The efficiency and titer of the library were
      85% and 3 x 10(5) pfu/ml, respectively. The library contained 1.3 x 10(5)
      individual recombinant phage whose foreign DNA inserted fragment size was 3.5 kb
      on average. CONCLUSION: The genomic DNA library constructed here can provide
      sufficient clone to cover H37Ra gene.

PMID- 10072802
TI  - [Advances in the study on sleep apnea syndrome and multiple organ injuries].

PMID- 10072803
TI  - [The clinical manifestation and drug sensitive tests of lower respiratory tract
      infection by enterobacter cloacae. The Pulmonary Infection and Fibrosis Group,
      Thoracic Society Shanghai Medical Association].
AB  - OBJECTIVE: To study the clinical characteristics of lowar respiratory tract
      infection caused by E. cloacae and to investigate the drug sensitivities of E.
      cloacae strains. METHOD: (1) Analysing the clinical deta of 58 case with lowa
      respiratory tract infection of enterobacter cloacae defined by a putative
      standard, including ages, symptoms, signs, underlying diseases, sputum culture, X
      ray findings and the prognosis. (2) Determining the drug sensitivities against
      the E. cloacae strains by K-B method. RESULTS: (1) There were 46 males and 12
      females, with the mean age 56 +/- 19% cases diagnosed, who had underlying
      diseases, most were COPD. 41% cases were mixed infections with other bacteria,
      most of which were P. aeruginosa and K. pneumoniae. The chief symptoms were fever
      (72%) and productive cough (87%). The chest X-ray revealed inflammatory
      infiltration in lower lobes of both sides. The mortality rate was 9%. (2) The
      antimicrobial tests in vitro showed that these strains were multiresistant to
      antibiotics, but imipenem, amikacin, tobramycin, ciprofloxacin, cefoaperazone
      were sensitive. CONCLUSIONS: The lower respiratory tract infections caused by E.
      cloacae showed no specific clinical manifestations. However, the mortality was
      high. The diagnosis should be made according to bacteriologic examination
      combined with clinical and X-ray manifestations. Combining antibiotics therapy
      was recommanded according to antimicrobial sensitivity test.

PMID- 10072804
TI  - [Pleural amyloidosis].
AB  - OBJECTIVE: To evaluate the clinical significance of systemic amyloidosis in the
      differential diagnosis of pleural effusion. METHOD: Retrospective analysis of the
      incidence and the characteristics of pleural effusion in systemic amyloidosis.
      RESULTS: Seven (47%) of 15 cases of systemic amyloidosis were complicated with
      pleural effusion, of them 4 cases were confirmed by positive Congo red stain of
      percutaneous pleural biopsies specimens. CONCLUSIONS: Systemic amyloidosis
      involving pleura was not rare. Pleural amyloidosis should be suspected in pleural
      effusion complicated by multiorgan disease. Percutaneous pleural biopsy with
      Congo red stain can confirm the diagnosis.

PMID- 10072805
TI  - [Role of pulmonary arterial angiotensin converting enzyme in development of
      hypoxic pulmonary hypertension].
AB  - OBJECTIVE: To study the effect of local pulmonary arterial renin-angiotensin
      system on hypoxic pulmonary hypertension(PAH). METHOD: Normobaric hypoxic PAH
      animal model was adopted. Systolic pulmonary arterial pressure(PAPs), pulmonary
      arterial angiotensin converting enzyme(ACE) activity, collagen content(HP) were
      measured and ultrastructure of pulmonary smooth muscle cells (SMC) and was
      observed. RESULTS: During hypoxia, PAPs, pulmonary ACE activity, HP increased
      significantly and SMC changed into secretive phenotype. Treatment with
      cilazapril, an ACE inhibitor, decreased ACE activity along with reversal of PAPs.
      HP and SMC phenotype. CONCLUSIONS: Pulmonary ACE participated in the modulation
      of changes of SMC phenotype and collagen metabolism during hypoxic PAH.

PMID- 10072806
TI  - [Cardiopulmonary effects of two modes of mechanical ventilation in dogs with and
      without acute lung injury-comparison of pressure regulated biphasic airway
      presure ventilation and intermittent positive pressure ventilation].
AB  - OBJECTIVE: To compare the cardiopulmonary effect of pressure regulated biphasic
      airway pressure (BiPAP) and intermittent positive pressure ventilation (IPPV).
      METHOD: Airway pressure, hemodynamics and blood gases were measured during the
      two ventilatory modalities with 0, 0.5, 1 kPa external end-expiratory pressure
      (EEP) in dogs with and without oleic acid-induced lung injury. RESULTS: No matter
      whether there is lung injury, airway pressure during BiPAP is lower compared with
      IPPV, but there is no difference in cardiac output. In dogs with lung injury,
      PaO2 during BiPAP is higher than that during IPPV. CONCLUSIONS: Compared with
      IPPV, BiPAP effected a decrease in airway pressure, and PaO2 was improved in dogs
      with lung injury, although the cardiac output was not increased.

PMID- 10072807
TI  - [Effects of 8-methoxypsoralen on smooth muscle of isolated human pulmonary
      arteries].
AB  - OBJECTIVE: To study the effect and mechanism of 8-methoxypsoralen (8-MOP)
      relaxing human pulmonary arteries. METHOD: Observe effects of 8-MOP on the
      isolated human pulmonary artery rings(PAR) obtained from 11 patients undergoing
      lobectomy for lung carcinoma. RESULTS: (1)8-MOP(2 x 10(-5) mol/L) caused
      significant relaxation of PAR precontracted with noradreline (NA) by 88% (P <
      0.001) and this effect of 8-MOP was independent on the endothelium of the
      pulmonary arteries. (2) The contraction of PAR induced by NA was significantly
      inhibited by 8-MOP(2 x 10(-5) mol/L) and the percentage of inhibition was 89% (P
      < 0.001). (3) The contractile dose-response curve of PAR induced by NA was
      shifted to the right and maximal contractile response was inhibited about 55% by
      8-MOP, PD'2 = 4.79. CONCLUSIONS: 8-MOP can significantly relax pulmonary arteries
      and 8-MOP may become an effective vasodilator for pulmonary hypertension.

PMID- 10072808
TI  - [The effects of cardiopulmonary bypass on pulmonary surfactant activity].
AB  - OBJECTIVE: To study the effects of cardiopulmonary by pass(CPB) on pulmonary
      surfactant (PS) activity. METHOD: In 12 children with patent ductus
      arteriosus(PDA) and 19 patients with ventricular septal defect (VSD), saturated
      phosphatidylcholine (SatPC), total phospholipids (TPL), total protein (TP) and
      surfactant protein-A(SP-A) in sequential airway aspirates before and after
      operation were determined. Tetroxide osmium digestion and neutral alumina column
      chromatography were used for SatPC, and a modified immunoblot method with a
      rabbit anti-human SP-A polyclonal antibody for SP-A measurment. RESULTS: In 19
      VSD patients with CPB, SatPC/TPL was significantly decreased from 48% to 34% (t =
      2.737, P < 0.05), SatPC/TP decreased from 64 to 33 mg/g (t = 3.011, P < 0.01),
      and SP-A from 23 to 11mg/g (t = 2.987, P < 0.01). In 12 patients without CPB,
      SatPC/TPL, SatPC/TP, SP-A/TP levels were not changed. CONCLUSIONS: CPB
      significantly reduces pulmonary surfactant activity.

PMID- 10072809
TI  - [A clinicopathological analysis in 46 elderly cases with cor pulmonale].
AB  - OBJECTIVE: To recognize the successful experience in diagnosis of cor pulmonale.
      METHOD: Autopsy records of 46 elderly patients with cor pulmonale were
      retrospectively analyzed. RESULTS: The average age of cor pulmonale in aged
      patients is 65. Most patients were died in the age of 70-79. The rates of
      incorrect diagnosis and mis diagnoss of cor pulmonale in elderly patients were
      27% and 6% respectively. Chronic bronchitis and chronic obstructive emphysema
      were the most commen causes of cor pulmonale in elderly patients with a rate of
      84%. The main cause of death were respiratory failure and heart failure with a
      rate of 53%. The average thickness of right ventricle wall increased with the
      course of cor pulmonale and the age of death. About 41% cor pumonale cases were
      combined with coronary heart disease. CONCLUSIONS: These results indicated that
      the rate of incorrect diagnoses of cor pulmonale in elderly patients was high,
      and great effort should be made to draw the clinician's attention for diagnose
      this illness correctly. The best way to reduce the incidence of cor pulmonale is
      to prevent and treat chronic bronchitis and chronic obstructive emphysema.
      Prevent and treat respiratory failure and heart failure effectively may decrease
      the mortality of cor pulmonale in elderly patients.

PMID- 10072810
TI  - [Diagnosis and surgical treatment for tuberculous bronchostenosis].
AB  - OBJECTIVE: To explore the appropriate diagnosis and treatment for tuberculous
      bronchostenosis patients who failed in anti-tuberculosis chemotherapy. METHOD:
      The 46 patients with tuberculous bronchostenosis were treated with pneumonectomy
      and bronchoplasty. The latter included pulmonary lobectomy, wedge and sleeve
      resection of primary bronchus. RESULTS: All the patients showed sputum negative
      conversion and were cured without anastomotic fistulae, stenoses and other
      complications. CONCLUSIONS: Pneumonectomy is a routine treatment for tuberculous
      bronchostenosis, and bronchoplasty is a good method for treatment of the disease.

PMID- 10072811
TI  - [Analysis of causes of drug resistance and therapeutic effects on 27 multi-drug
      resistant pulmonary tuberculosis patients].
AB  - OBJECTIVE: To analyse the causes of multi-drug resistant tuberculosis (MDR-TB)
      and to evaluate the effects of chemotherapy with ofloxacin and other
      antituberculosis drugs. METHOD: 27 cases with MDR-TB were treated with the
      regimen of 3KPTHOX/PTHOX. Changes of sputum convesion, X-ray manifestations and
      side effects after the treatment were also evaluated. RESULTS: 67% of the MDR-TB
      patients were due to irregular treatment, and 18% were caused by improper
      treatment. The sputum culture conversion rate at end of treatment was 89%. The
      bacteriological relapse rate of converted cases during 2 year follow-up was 8%.
      CONCLUSIONS: MDR-TB might be prevented by a combination of health education and
      rational use of short-course chemotherapy. Ofloxacin and other second-line anti
      tuberculosis drugs are effective and were tolerated in treating patients with MDR
      TB.

PMID- 10072812
TI  - [Implementation of mid-term national tuberculosis control programme].
AB  - OBJECTIVE: To evaluate the implementation of mid-term National Tuberculosis
      Control Programme (NTP). METHOD: The construction of tuberculosis control
      organizations, implementation of tuberculosis control work, etc, were
      investigated retrospectively. RESULTS: Almost all the tuberculosis control
      indices had reached the mid-term NTP target except the case-finding index.
      CONCLUSIONS: Much more efforts are required to reach the NTP target of year 2000
      that the prevalence of smear positive pulmonary tuberculosis decrease to 70 per
      100,000 populations.

PMID- 10072813
TI  - [Current studies on airway inflammation in chronic obstructive pulmonary
      disease].

PMID- 10072814
TI  - [Diagnosis and therapy of extrapulmonary tuberculosis].

PMID- 10072815
TI  - [Development and application of the method for controlling contamination of tumor
      samples with normal cells to detect deletion of P16 gene in primary lung
      carcinoma].
AB  - OBJECTIVE: The method is to be established to effectively promote the sensitivity
      of the detection of P16 gene deletion from tumor tissues mixed with normal cells
      and to determine the relationship between the gene alteration and the lung
      cancers. METHODS: The normal DNA and that of MCF-7 cells with P16 gene deletion
      was proportionally mixed and the mixture was limitedly diluted. The exon2 of P16
      gene and internal control gene fragment were amplified with template of various
      amounts of DNA. And polymerase chain reaction (PCR) technique was used in the
      amplification of exon2 of P16 gene with certain amount of lung cancer DNA as the
      templates. The amplified fragment was analyzed with SSCP. RESULTS: Normal DNA did
      not contaminate P16 gene deletion when DNA template was 5 ng and normal cells
      less than 40%. No deletion and mutation of P16 gene was found in the small cell
      lung cancer and normal cancer-surrounding lung tissues, while P16 gene deletion
      and mutation were found respectively in 21 and 3 cases of 52 cases of non-small
      cell lung cancer. The rate of P16 gene deletion (72%) in lung cancer with
      lymphatic involvement was significantly higher than that in lung cancer without
      the metastasis (16.8%) (P < 0.05). It is found that P16 gene deletion was
      markedly associated with pathologic manifestation and prognosis of non-small cell
      lung cancer (P < 0.05). CONCLUSIONS: Controlling of the amount of template DNA in
      PCR helps to promote the sensitivity of detection of P16 gene deletion. The
      abnormality of P16 gene might relate to the malignant development of non-small
      cell lung cancer.

PMID- 10072816
TI  - [Preliminary study on relationship among apoptosis and related gene, prognosis of
      lung cancer].
AB  - OBJECTIVE: To observe the relationship among Lung cancer cell apoptosis,
      proliferation and related gene expression and its significance as an index of
      prognosis. METHOD: In situ end labelling (ISEL) technique and DNA gel
      electrophoresis were used to detect the apoptotic cell, immunohistochemistry was
      used to detect the expression of bcl-2, P53 and ki-67 in 57 cases of Lung cancer.
      RESULT: The number of apoptotic cells was found to correlated with the ratio of
      ki-67 positive cell (P = 0.001). There was significant correlation between the
      extent of apoptosis and the expression of bcl-2 in SCLC, but this relation was
      not observed in NSCLC. No correlation was found among apoptotic cells or ki-67
      positive cells, staging, age and expression of P53. Patients with apoptotic cells
      greater than 3% and ki-67 greater than 20% possessed shorter survival time than
      that less than or equal to 3% or 20%, respectively (P = 0.0057, P = 0.002 by log
      ronk). CONCLUSIONS: Increased apoptotic and proliferous cells are independent
      prognostic index in lung cancers, predicting shortened survival time of the
      patients.

PMID- 10072817
TI  - [Clinical study of polymerase chain reaction technique in the diagnosis of bone
      tuberculosis].
AB  - OBJECTIVE: To evaluate the clinical value of polymerase chain reaction (PCR)
      technique in diagnosis of bone tuberculosis. METHODS: PCR, standard light
      microscopy and standard culture technique were used to detect Mycobacterium
      tuberculosis in samples obtained from 60 patients with bone tuberculosis and 20
      patients without bone tuberculosis. In the meantime, some factors affecting PCR
      result were analysed and methods to deal with them were discussed. RESULTS: In
      the group of 60 patients with bone tuberculosis, the positive rate was 83% in PCR
      technique, 3% in standard light-microscope technique and 7% in the standard
      culture technique. A statistically obvious difference was seen (P < 0.005). In
      the group of 20 patients without bone tuberculosis, 2 cases showed positive in
      PCR technique, none in the other methods. Specificity of PCR technique in a blind
      comparison study indicated 100%. The whole process of PCR amplification is fully
      automatic and can be finished within several hours, and the detection time is
      considerably reduced. CONCLUSIONS: PCR technique is a rapid, specific, sensitive
      and simple method for detection of mycobacterium tuberculosis in sample of bone
      tuberculosis, and it is of great value in the diagnosis of bone tuberculosis and
      differentiating bone tuberculosis from other bone diseases.

PMID- 10072818
TI  - [Laboratory diagnosis of tuberculous peritonitis].
AB  - OBJECTIVE: To evaluate the diagnostic value of polymerase chain reaction (PCR)
      assay in combination with Southern hybridization technique and enzyme-linked
      immunosorbent assay (ELISA) in tuberculous peritonitis. METHODS: Fourty-two
      tuberculous ascites were detected for M. tuberculosis by PCR technique in
      combination with Southern hybridization, in which nuclear acid probe was
      digoxigenin-labeled, and the result was compared with conventional
      bacteriological methods and ELISA. IS6110, a specific insert sequence of M.
      tuberculosis, was used as primer. The specificity of PCR products was confirmed
      by hybridization and digestion with Sal I restrictive endonuclerase, and the
      sensitivity of hybridization was compared with gel electrophoresis. RESULTS: The
      sensitivities were 69% by PCR, 71% by ELISA, 9% by culture and 0 by acid fast
      staining respectively. Hybridization was found more sensitive than gel
      electrophoresis. CONCLUSIONS: Both PCR technique and ELISA are valuable in
      diagnosis of tuberculous peritonitis, and the former is more specific than the
      latter. PCR technique in combination with Southern hybridization can improve both
      the sensitivity and the specificity of dectection.

PMID- 10072819
TI  - [The role of nitric oxide in the pathogenesis of asthma].
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) in the pathogenesis of
      asthma, we observed the influence of L-NG-arginine-methylester (L-NAME), the
      inhibitor of nitric oxide synthase (NOS), on the contraction of isolated guinea
      pig tracheal smooth muscles and observed the changes of NOS in the guinea pig
      asthma model lung tissues using histochemical detection. METHODS: Male Hartley
      guinea pig isolated tracheal ring were incubated with L-NAME 2.0 mmol/L for 30
      min and histamine was given to make a concentration response curve. The sections
      of guinea pig asthma model lung tissues were stained with NADPH diaphorase.
      RESULTS: The histamine concentration response curve was significantly shifted
      upward in the L-NAME incubated group, the maximal response increased by 170%
      compared with that of control group. The numbers of alveolar macrophages were
      significantly increased and NADPH diaphorase staining was positive in asthma
      model group, in contrast, the alveolar macrophages were hardly seen and there was
      almost no positive staining of NOS in the control group. CONCLUSIONS: The
      inhibition of NO synthesis of guinea pig respiratory tract with L-NAME results in
      a marked increase in airway contraction in vitro after histamine provocation.
      This result indicate that NO has relaxant effect on tracheal smooth muscles and
      may decrease airway responsiveness to histamine. The increased alveolar
      macrophages and positive stained NOS in the lung tissues of asthma model indicate
      that NO, which is synthesized by the NOS in alveolar macrophages, may play an
      important role in asthma pathogenesis.

PMID- 10072820
TI  - [Hemodynamic response to exercise in patients with chronic obstructive pulmonary
      disease (COPD)].
AB  - OBJECTIVE: The present study was undertaken to assess the cardiopulmonary
      response during the initial period of exercise. METHODS: Eight patients with COPD
      and 10 normal subjects were investigated during exercise (35W) in room air and
      oxygen breathing for 15 minutes, respectively. Pulmonary arterial mean pressure
      (mPAP), cardiac output (CO) and mixed venous oxygen saturation (SvO2) were
      measured by Swan-Ganz catheter during exercise. RESULTS: Compared with normal
      controls, mPAP in COPD patients was increased and SvO2 decreased markedly both in
      room air and oxygen breathing during exercise. And CO increased relative slowly
      than that of normal controls. Furthermore, in patients with COPD, the time to
      reach their steady state in mPAP and SvO2 during exercise were delayed compared
      with normal controls. Moreover, we found that the time to reach their steady
      state in mPAP and SvO2 were shortened when the patients were given oxygen
      breathing during exercise. CONCLUSIONS: The results indicate that the measurement
      of initial changes in mPAP and SvO2 during exercise have important clinical
      significance for evaluating the cardiopulmonary response in patients with COPD.

PMID- 10072821
TI  - [Clinical and pathological manifestations in 129 patients with tuberculous
      meningitis].
AB  - OBJECTIVE: To investigate the diagnosis of tuberculous meningitis. METHOD: One
      hundred twenty-nine cases of tuberculous meningitis proved by autopsy, from the
      year 1952 through 1994, were retrospectively reviewed. RESULTS: Sixty-four cases
      were misdiagnosed before death, and the misdiagnosis rate was 49.6%. Among these
      misdiagnosed cases, 34 were misdiagnosed as other brain diseases, and the other
      30 cases were misdiagnosed as severe pulmonary tuberculosis, severe pneumonia,
      gastric cancer, rheumatic heart disease, cor pulmonale and leukemia, etc. The
      main clinical manifestations included meningitis and extra-cerebral tuberculous
      syndromes. The cerebral spinal fluid changes included pressure increase,
      elevation of cell counts and protein content, decrease of glucose and chlorides.
      Both cerebral CT and intensified scan showed miliary tubercles in the brain
      parenchyma. High density stellate type of shadows in the basal surface of the
      brain, interpedunclar forsa and cerebral fissures, enlargement of brain
      ventricles, cerebral edema and thrombosis were also shown. Tuberculous lesions in
      the meninges, brain parenchyma, brain ventricles and brain blood vessels were
      found by autopsy. CONCLUSION: The clinical manifestations, cerebral spinal fluid
      examination, in combination with CT scan of the head, and searching for
      extracerebral tuberculous foci are the basis for the diagnosis of tuberculous
      meningitis.

PMID- 10072822
TI  - [Long-term efficacy of full course intermittent short-course chemotherapy on new
      smear positive tuberculosis patients].
AB  - OBJECTIVE: To evaluate the long-term efficacy of full course intermittent short
      course chemotherapy [2H3R3Z3S3(E3)/4H3R3], which has first been used in the
      National Tuberculosis Control Programme with the loan from the World Bank and its
      satisfactory short-term efficacy has been achieved, on new smear positive
      tuberculosis patients. METHOD: All new smear positive tuberculosis patients,
      registered by 56 counties of 12 project provinces and autonomous regions in 1992,
      were investigated to find out the bacteriological relapse rate 2 years after
      treatment. RESULT: One hundred thirty five out of 4400 patients followed up were
      found smear positive, with a relapse rate of 3.1%. CONCLUSION: The result
      suggests that the chemotherapy should be given a priority in the National
      Tuberculosis Control Programme because of its high cure rate.

PMID- 10072823
TI  - [Epidemic trend of tuberculous meningitis in children of Heilongjiang province].
AB  - OBJECTIVE: To investigate the epidemic trend of tuberculous meningitis in
      children of Heilongjiang province in recent ten years, and to provide scientific
      evidence for control of the disease. METHODS: The data, registered by 82
      counties' antituberculosis institute, of tuberculous meningitis patients under 14
      years were analyzed, and the epidemic trend of the disease was also discussed.
      RESULTS: The incidence of tuberculous meningitis was 9.58 per 10,0000 populations
      in 1982, 2.17 per 10,0000 populations in 1992. The rate of annual decrease was
      13.8%. CONCLUSION: Participation of the government, improvement of pelple's life
      standard, control of sources of infection, and vaccination of BCG are effective
      measures for decreasing the incidence of this disease.

PMID- 10072824
TI  - [Diagnosis and treatment of hepatic tuberculoma].
AB  - OBJECTIVE: To explore the appropriate diagnosis and treatment for hepatic
      tuberculoma. METHOD: Eight cases with hepatic tuberculoma confirmed
      pathologically were reported and analyzed. RESULTS: Five of the eight cases were
      misdiagnosed as other types of hepatic tumor, and only 3 cases correctly
      diagnosed preoperatively. All cases underwent segmentectomy or local resection,
      and no relapse was found after four-year follow-up in seven cases. CONCLUSIONS:
      The cases with hepatic occupying-space lesions who had tuberculosis history
      should be suspected of being hepatic tuberculoma; The aspiration liver biopsy
      guided by B-mode ultrasound and CT scan can provide correct diagnosis; The
      segmentectomy and local resection are effective and practicable for treatment of
      hepatic tuberculoma, and the antituberculosis drugs should be administrated
      postoperatively so as to strengthen the therapeutic effect.

PMID- 10072825
TI  - [Molecular basis of rifampin resistance in mycobacterium tuberculosis].

PMID- 10072826
TI  - [Systemic inflammatory response syndrome and acute lung injury, multiple organ
      dysfunction syndrome].

PMID- 10072827
TI  - [Mechanical ventilation therapy with permissive hypercapnia on ARDS].
AB  - OBJECTIVE: Study of mechanical ventilation (MV) therapy of ARDS (acute
      respiratory distress syndrome). METHODS: Ten cases of ARDS were observed.
      Depending on patients' kidney compensation for respiratory acidosis, low tidal
      volume (VT, mean = 6.5 ml/kg) was used and certain respiratory acidosis was
      permitted in order to decrease airway plateau pressure and lung barotrauma. On
      the premise of keeping patients' PaO2 about 7.3 kPa (1 kPa = 7.5 mmHg), lowest
      possible FiO2 (mean = 0.51) and PEEP (mean = 0.92 kPa, 1 kPa = 10.2 cmH2O) were
      used. RESULTS: Seven of the ten survived. Three of them had respiratory acidosis
      and two had lung barotrauma during MV. CONCLUSION: Using lower VT and permitting
      certain respiratory acidosis are worthy to be considered in MV therapy of ARDS.

PMID- 10072828
TI  - [Effects of permissive hypercapnia on cardiopulmonary function in acute lung
      injury model].
AB  - OBJECTIVE: To observe the effects of permissive hypercapnia on cardiopulmonary
      function in oleic acid induced acute lung injury (ALI) models. METHOD: ALI models
      of pigs were induced successfully by infusing oleic acid, Swan-Ganz cathether was
      used for monitoring hemodynamics and different low tidal volumes were set for
      variable hypercapnia. RESULTS: ALI was characterized by an increase in airway
      pressure and a decrease in static compliance (Cst), artery oxygen tension (PaO2),
      oxygenation index and cardiac output. There was also an increase in mean
      pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), systemic
      vascular resistance (SVR) and shunt fraction. After using 0.98 kPa (1 kPa = 10.2
      cmH2O) PEEP, some of cardiopulmonary functions were improved. While reduced tidal
      volume to 7.7 +/- 0.3 ml/kg and PaCO2 increased to 9.44 +/- 1.27 kPa (1 kPa = 7.5
      mmHg), which caused neither a change in PaO2/FiO2, PaO2, Cst nor in SVR, PVR but
      an increase in cardiac output. Though ventilation setting did not change except
      for the reducing tidal volume to 6.1 +/- 0.6 ml/kg and PaCO2 reached 12.1 +/-
      1.05 kPa, then various adverse effects on cardiopulmonary system were observed.
      CONCLUSION: It seems that mechanical ventilation with permissive hypercapnia was
      safe at certain level.

PMID- 10072829
TI  - [Study on the chemotaxis and DNA synthesis of pulmonary artery smooth muscle
      cells].
AB  - OBJECTIVE: To explore the effect of hypoxia on the proliferation and migration of
      pulmonary vascular smooth muscle cells (PVSMC), and whether migration of PASMC is
      involved in the pathogenesis of pulmonary vascular remodeling associated with
      hypoxia. METHODS: In this study, the effect of PDGF, ANP and hypoxia on DNA
      synthesis and chemotaxis of cultured neonatal calf pulmonary artery smooth muscle
      cells (PASMC) is investigated by 3H-thymidine incorporation and measurement of
      cell migration using a 48-well Boyden chamber respectively. RESULTS: The results
      demonstrated that hypoxia could stimulate DNA synthesis and chemotaxis of PASMC
      induced by PDGF; ANP could inhibit DNA synthesis and chemotaxis of PASMC by a
      cGMP dependent pathway. CONCLUSIONS: It is suggested that PDGF, ANP and hypoxia
      play important roles in regulating the proliferation and migration of PASMC,
      which is important in the pathogenesis of hypoxic pulmonary vascular remodeling.

PMID- 10072830
TI  - [The long-term effect of nifedipine (control release tablets) in patients with
      chronic obstructive pulmonary disease and cor pulmonale].
AB  - OBJECTIVE: To observe the long-term effect of nifedipine (control release
      tablets) in patients with chronic obstructive pulmonary disease and cor
      pulmonale. METHODS: A randomized, double blind, placebo-controlled design was
      made, two hundred and two patients (FEV1/FVC was 47.35% +/- 8.10%) were divided
      into two groups: nifedipine group (20 mg Bid) 102 cases, placebo group (one
      tablet Bid) 100 cases. RESULTS: The equilibrium test between both groups was
      comparable. Two-year follow-up rates of both groups were 94% and 89%,
      respectively. The comparision of the nifedipine to placebo group was as follows:
      in nifedipine group, the improvement of dyspnea, fatigue and exercise capacity
      showed significantly better results (P < 0.05); FEV1 and PaCO2 deterioration was
      unremarkable (P > 0.05); the pulmonary impedance plethysmogram B-Y1 that reflects
      pulmonary vascular compliance appeared significant improvement (P < 0.05) and the
      mortality of the disease that was the most important observation endpoint was
      declined (P = 0.051), but some electrocardiographic index reflected right
      ventricular load became worse (P < 0.05). CONCLUSIONS: Long-term taking
      controlled release-nifedipine is a safe, effective measure which might improve
      life quality and decrease mortality in patients with chronic obstructive
      pulmonary disease and chronic cor pulmonale, however the drug can not slow down
      or reverse the progress of this illness.

PMID- 10072831
TI  - [Efficacy of prostaglandin E1 in treatment of cor pulmonale patients with heart
      failure].
AB  - OBJECTIVE: To investigate the effects of prostaglandin E1 (PGE1) by intravenous
      drip in cor pulmonale patients with heart failure. METHODS: Thirty caseas of cor
      pulmonale with heart failure were treated with PGE1 at a dose of 200 micrograms.d
      1 for 5 days and in 30 patients with cor pulmonale heart failure (no PGE1) and in
      20 healthy subjects as controls. The level of serum endogenous digoxin-like
      factor (EDF), serum lipoid superoxide (LPO), serum superoxide dismutase (SOD) and
      blood PaO2, PaCO2 were determined. Their symptoms and signs were observed before
      and after treatment. RESULTS: The level of serum EDF, LPO were significantly
      increased (P < 0.001) and serum SOD was significantly decreased (P < 0.001) in
      PGE1 group and controls group (no PGE1) as compared with healthy subjects. In
      PGE1 group the level of serum EDF, LPO were markedly decreased (P < 0.001), and
      serum SOD was markedly elevated (P < 0.001), and their symptoms, signs and blood
      gas parameters had noteworthyly improved (P < 0.01-0.001). But in the control
      group (no PGE1) the level of serum EDF, LPO, SOD, blood gas parameters and their
      symptoms and signs, showed no significant difference (P > 0.05). CONCLUSIONS:
      PGE1 is effective in therapy of cor pulmonale with heart failure. Treatment with
      PGE1 shows more significant benefits in cor pulmonale patients with heart
      failure.

PMID- 10072832
TI  - [Analysis of 37 cases of pneumonia of Legionnaires' disease].
AB  - OBJECTIVE: To heighten our awareness of pneumonia of Legionnaires' disease (LP).
      METHODS: 37 cases of LP were reviewed. RESULTS: Besides the characteristics of
      pneumonia, extrapulmonary manifestations, including gastrointestinal, hepatic,
      renal and neurologic abnormalities, occurred in 35% of the patients, pleural
      effusion was more common (40%), 38% and 17% of the patients showed hyponatremia
      and pulmonary abscess respectively. Roentgenographic changes appeared to last
      longer and resoluted later than the clinical improvement occurred. CONCLUSION:
      Erythromycin shows good effects in treating LP.

PMID- 10072833
TI  - [Assessment of sputum culture and serology for detection of chlamydia pneumoniae
      in patients with symptomatic acute respiratory tract infection].
AB  - OBJECTIVE: To evaluate sputum culture and serology for detection of chlamydia
      pneumoniae (C. pneumoniae) in adult patients with acute respiratory tract
      infection and normal subjects. METHODS: Microimmunoflorescence (micro-IF) test
      for IgG and IgM antibodies to C. pneumoniae specific antigen was performed in
      every subject. Thirty-seven patients also had sputum HEP-2 cell culture tested
      for C. pneumoniae. RESULTS: Twenty-six patients (29.7%) with micro-IF IgG titres
      equal to or greater than 1:512 or/and IgM titres equal to or greater than 1:32
      indicated recent infection. Eight patients (21.3%) with positive sputum culture
      of C. pnuemoniae were identified. No similar titer was shown in control normal
      subjects. CONCLUSIONS: Acute infection of C. pneumoniae was common in symptomatic
      patients with acute respiratory tract infection and attention should be drawn to
      this special illness.

PMID- 10072834
TI  - [Experimental study on the antituberculous activity of ofloxacins].
AB  - OBJECTIVE: To compare the antituberculous activities of ofloxacins (OFLX) made by
      different pharmaceutical companies. METHODS: The minimal inhibitory
      concentrations (MIC) of OFLX were determined by two-fold dilution method. The
      efficacy of OFLX was compared in terms of median survival time (ST50) against M.
      tuberculosis infection in mice. RESULTS: In vitro the activities against M.
      tuberculosis (H37Rv), M. bovis (Ravenel) and M. Phlei products showed similar
      degree. The MICs of OFLX were 0.5-1.0 microgram/ml in modified Sauton medium and
      1.0 microgram/ml in modified Lowenstin-Jensen medium. OFLX was more active than
      ethambutol (MIC 4-8 micrograms/ml, 2.0 micrograms/ml, respectively) against M.
      tuberculosis in the same media. OFLX from domestic or foreign drug companies
      showed similar results for treating M. tuberculosis infection in mice and all
      were significantly effective. The efficacy of OFLX at the dose of 4 mg per mouse
      was found close to that of ethambutol (EMB) at the dose of 2 mg per mouse. The
      efficacy of OFLX at the dose of 2 mg per mouse close to EMB at the dose of 1 mg
      per mouse and thiacetazone at the dose of 2 mg per mouse. CONCLUSIONS: In vitro
      and in vivo, the activities of OFLX from different sources against M.
      tuberculosis are about the same.

PMID- 10072835
TI  - [Methods for detecting mycobacterium tuberculosis in the air of wards for
      tuberculosis patients].
AB  - OBJECTIVE: To explore useful methods for detecting M. tuberculosis in the air of
      inpatient's wards of tuberculosis. METHODS: Thirty samples were collected by
      using LWC-I air sampler from the air of wards housing sputum positive patients.
      The samples were washed with 0.85% sodium chloride solution, then centrifuged,
      and finally detected M. tuberculosis by L-J medium culture, BACTEC method, guinea
      pig experiment, PCR and Southern blotting. RESULTS: The positive rates by PCR and
      Southern blotting were 47% (14/30) and 60% (18/30) respectively. In the
      experimental group containing 30 guinea pigs, two were positive by culture from
      the animal tissues (spleens or lungs), and another one was pathologically
      positive. Ten guinea pigs in control group were negative. Thirty samples were all
      negative by L-J and BACTEC. CONCLUSIONS: It is indicated that using air sampling
      to detect M. tuberculosis in the air is practicable. PCR and Southern blotting
      are very helpful in detecting M. tuberculosis in the air because they have the
      advantages of high sensibility and specificity, and they remarkably shorten the
      time of detection. Animal experiment can provide compensation to PCR and Southern
      blotting.

PMID- 10072836
TI  - [Clinical investigation on 42 cases of pulmonary tuberculoma].
AB  - OBJECTIVE: For the purpose to find the possible reasons causing pulmonary
      tuberculoma been misdiagnosed as lung cancer. METHODS: Clinical symptoms, chest X
      ray films, tomographic and CT manifestations as well as laboratory data of 42
      cases of pulmonary tuberculoma pathologically proved were thoroughly reviewed.
      All the radiological appearances were compared with pathological findings.
      RESULTS: Shallow lobulated contour, spurlike shadow formation, vacoule sign,
      satellite lesions, pleural involvement, calcified spots were found very important
      for differential diagnosis of these 2 diseases. CONCLUSIONS: It is difficult to
      differentiate pulmonary tuberculoma from lung cancer. By paying special attention
      to the above mentioned appearance, evaluating them very carefully and considering
      them with positive laboratory findings, it might be possible to avoid
      misdiagnosis before surgical operation.

PMID- 10072837
TI  - [Preliminary observation of MRI manifestations of adult pulmonary tuberculosis].
AB  - OBJECTIVE: To study the role of MRI in diagnosis of adult pulmonary tuberculosis.
      METHODS: MRI and X-ray appearance of 55 adult pulmonary tuberculosis cases were
      reviewed. RESULTS: No obvious difference was found between the images of MRI and
      chest radiography which reflect infiltrative and proliferative pathologic changes
      of pulmonary tuberculosis (including cavity, tuberculoma and caserous
      pneumonitis). Infiltrative, proliferative lesions and caserous pneumonitis showed
      middle signal on the T1 and T2 weighted images. Cavity showed low signal.
      Tuberculoma showed generally hyterogenous signal on the T2 weighted images.
      CONCLUSION: It is unnecessary to use MRI as a routine tool for diagnosis of
      pulmonary tuberculosis.

PMID- 10072839
TI  - [Molecular markers in cancer and their clinical significance].

PMID- 10072838
TI  - [Adrenomedullin and lung disease].

PMID- 10072840
TI  - [Interleukin-6 behaves as an autocrine growth stimulator for a human lung giant
      cell carcinoma cell line].
AB  - OBJECTIVE: To study the effect of interleukin-6 (IL-6) on the growth of human
      pulmonary giant cell carcinoma cell line PG in vitro. METHODS: IL-6 mRNA level
      was detected by means of reverse transcriptase polymerase chain reaction (RT-PCR)
      and IL-6 receptor (IL-6R) mRNA was analyzed using Northern blotting
      hybridization. The production of IL-6 was detected by bioactive assay. The
      biological role of IL-6 produced by PG cells was assessed with anti-IL-6
      neutralizing antibodies. RESULTS: PG cells expressed IL-6R mRNA. Recombinant
      human IL-6 promoted the proliferation of PG cells. PG cells also expressed IL-6
      mRNA and produced bioactive IL-6. Treatment of PG cells with anti-IL-6 antibodies
      resulted in reduced growth of PG cells. CONCLUSION: The results indicate that IL
      6 behaves as an autocrine growth stimulator for PG cells in vitro.

PMID- 10072841
TI  - [Astrogliosis and basic fibroblast growth factor].
AB  - OBJECTIVE: To study the relationship between reactive astrogliosis and its
      autocrine bFGF. METHODS: On the primary astrocyte culture with mechanical
      scratch, the dynamic expression of bFGF, PCNA, GFAP and GFAP-mRNA were determined
      by immunocytochemistry and in situ hybridization. RESULT: Astrocytes at the edge
      of the injury began to express bFGF 2 hours after scratching and reached its peak
      by the 12th hour, then declined after 2 days. GFAP-mRNA was detectable in
      astrocytes near the injury from the 6th hour and reached its peak within 24
      hours. A few hypertrophic astrocytes in the injured area expressed GFAP-mRNA on
      the 3rd day. Enhanced GFAP expression of astrocytes was observed with hypertrophy
      of cytoplasma which extended wide processes into the injured area from the day of
      the scratch and reached its peak on the 2nd day. On the 3rd day, the previously
      injured area was covered with hypertrophic astrocytes. PCNA was expressed 2 hours
      after damage by some of the astrocytes in the vicinity of injury. CONCLUSION:
      Autocrine bFGF was the early response of reactive astrocytes and bFGF may act as
      promoter of reactive astrogliosis. Enhanced GFAP expression was the result of
      upregulation of GFAP-mRNA. The prominent event of reactive astrogliosis was the
      hypertrophy of astrocytes.

PMID- 10072842
TI  - [Expression and antagonist role of endothelin and nitric oxide synthase in
      atherosclerotic plaque].
AB  - OBJECTIVE: To study the pathogenetic mechanism of atherosclerotic plaque, the
      action of mediation and antagonism of endothelin (ET) and nitric oxide synthase
      (NOS) was investigated. METHODS: In situ hybridization, RT-PCR on endothelin and
      NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model
      and cultured vascular smooth muscle cells (VSMC) from normal rabbit. RESULTS:
      Transcription of endothelin mRNA increased and transcription of NOS mRNA
      decreased in astherosclerotic plaque: compared with normal aorta, expression of
      ET gene in plaque was increased by 1.2 times and the expression of NOS gene was
      decreased by 22.2%; cytochemistry combined with image pattern analysis showed
      that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist
      of ET could inhibit the role of ET which causes a decrease of NOS protein in
      VSMC. CONCLUSION: The imbalance between NOS and ET, namely abnormal increase of
      ET and/or obvious decrease of NOS, is related to atherosclerotic plaque
      formation.

PMID- 10072843
TI  - [Regulatory effects of cAMP analogs on growth and differentiation of metastatic
      human lung cancer cells].
AB  - OBJECTIVE: To study the effects of two cAMP analogs with different site
      selectivity on growth and differentiation of metastatic human lung cancer cells.
      METHODS: The methods used include cell culture, in vitro invasion assay, soft
      agar colony formation assay, immunocytochemistry and electron microscopy. A
      metastatic human lung cancer cell line gwas treated with dibutyryl cAMP (db-cAMP,
      non-site-selective) or 8-chloro-cAMP (8-Cl-cAMP, site-selective for type II PKA).
      RESULTS: Treatment of PG cells with 1 mmol/L of db-cAMP for 7 days resulted in
      48% growth inhibition, while treatment with 20 mumol/L of 8-Cl-cAMP gave 70%
      growth inhibition. The growth inhibitory effect of db-cAMP was shown to be
      reversible, while that of 8-Cl-cAMP was not. The ability of PG cells to penetrate
      matrigel-coated membrane and to form colonies in soft agar was also significantly
      inhibited by treatment with these two drugs. Microscopic observation showed that
      cells formed elongated cytoplasmic processes and increased expression of neuron
      specific enolase as well as chromogranin after treatment. CONCLUSION: The
      objective to inhibit malignancy could be reached by activation of specific PKA
      with site-selective cAMP analogs.

PMID- 10072844
TI  - [A study on expression of fibronectin receptor alpha 5 beta 1 of Ito cells in
      experimental liver fibrosis in rats].
AB  - OBJECTIVE: The study was designed to study the role of fibronectin (FN) receptor
      alpha 5 beta 1 in liver fibrogenesis. METHODS: Northern blot analysis and
      immunohistochemical techniques were used to observe the in vivo and in vitro
      changes in the expression of FN and its receptor alpha 5 beta 1 in CCl4 induced
      rat liver fibrosis in Ito cells. RESULTS: (1) alpha 5 beta 1 was mainly detected
      in the endothelia and some of the desmin (DM) positive cells (Ito cells) of the
      sinusoids in normal rat liver. The expression of alpha 5 beta 1 of DM positive
      cells in the experimental groups was enhanced and reached their peaks by the 10th
      week. The changes in FN was similar to that of alpha 5 beta 1; (2) The expression
      of FN, alpha 5 and beta 1 mRNA of the liver in the experimental groups detected
      by Northern blot analysis was increased and reached their peaks by the 6th week.
      The content of these mRNAs of the cultured Ito cells isolated from the
      experimental group was increased more than that from normal liver specimens.
      CONCLUSION: Ito cells expressed FN receptor alpha 5 beta 1. The activation of Ito
      cells resulted in the increase of the expression of the three mRNAs during
      fibrogenesis. It is suggested that the detection of gene transcription of FN and
      its receptor mRNAs by Northern blot analysis could reveal the activation and
      proliferation of Ito cells and thereby provides a sensitive signal of liver
      fibrosis.

PMID- 10072845
TI  - [The expression of costimulating molecule B7.1 in lymphoma tissues].
AB  - OBJECTIVE: To study the expression of immuno-costimulating molecule B7.1 in
      lymphoma tissue and its part in immuno escape mechanism. METHODS: Using the RT
      PCR and in situ hybridization (ISH) techniques, the expression of B7.1 molecule
      in 12 fresh and 23 paraffin embedded tissues were studied. RESULTS: (1) B7.1 mRNA
      transcription was detected in 10/12 lymphoma tissues by RT-PCR; (2) mRNA
      expression in 16/23 lymphoma tissues was detected by ISH with Dig-labelling B7.1
      cDNA probe. Alternatively, a 450bp by transcript that was relevant to the normal
      B7.1 molecule was cloned and studied by RT-PCR and ISH respectively. CONCLUSION:
      More in depth studies should be performed on the relation between the transcript
      molecule and lymphoma and its effect on tumor immunity.

PMID- 10072846
TI  - [The significance of detecting Epstein-Barr virus BNLF1 fragment and its
      expression in Hodgkin's disease in the Guangdong area].
AB  - OBJECTIVE: To study the association between Epstein-Barr virus (EBV) and
      lymphoma. METHODS: PCR, in situ hybridization and immunohistochemistry were used
      to detect the presence of EBV in 51 cases of Hodgkin's disease in the Guang dong
      area. RESULTS: The detection rate of EBV-BNLF1 fragment by PCR was 80.4%,
      significantly higher than that of reactive hyperplasia of lymph nodes (RHLN).
      Cloning and sequence analysis revealed the PCR product to be BNLF1 fragment, but
      no mutation was found. In situ hybridization (ISH) demonstrated EBV in the nuclei
      of malignant and non-malignant cells in 15 of the 41 PCR-positive cases. The
      expression product of BNLF1 gene-latent membrane protein (LMP1) was detected in
      25 of the 51 cases of HD (49%) and the staining was restricted to the tumor
      cells. The detection rates of BNLF1 fragment and its expression in the 15 cases
      of HD under 20 years of age were much higher that those in HD over 20 years of
      age and RHLN of the same age group (P < 0.01). CONCLUSION: There was EBV
      infection and expression of its latent membrane protein in the tumor cells in
      half of the HD cases and may play a role in the genesis and development of HD.
      The results also suggest that HD in children and adolescence being more closely
      correlated with EBV latent infection.

PMID- 10072847
TI  - [The correlation of TGF-alpha, EGFR in precancerous lesions and carcinoma of
      stomach with PCNA expression].
AB  - OBJECTIVE: To assess the changes and possible role of expression of TGF-alpha and
      EGFR in gastric carcinogenesis and its relationship with PCNA labelling index
      (PCNA LI). METHODS: Immunohistochemical study using LSAB kit. RESULTS: (1) The
      expression of TGF-alpha was increased in normal mucosa and metaplastic tissue
      near the carcinoma when compared with non-cancer controls (P < 0.01). (2)
      Increased expression of EGFR was found in the intestinal metaplastic and
      dysplastic areas compared with nomral mucosa and carcinoma tissue (P < 0.01). (3)
      Coexpression rate of TGF-alpha and EGFR was higher in dysplasia than in other
      tissues (P < 0.01). (4) There was a close correlation between the intensities of
      TGF-alpha, EGFR and PCNA. (5) The expression of TGF-alpha, EGFR and PCNA was not
      related to infiltration and lymph node metastasis of gastric carcinoma.
      CONCLUSION: The increased expression of EGFR, TGF-alpha may serve as an important
      molecular marker of gastric premalignant lesions when combined with measurement
      of PCNA LI and may be of assistance in screening of early gastric carcinoma in
      high risk populations.

PMID- 10072848
TI  - [The correlation between expression of oncogene protein products p53, p21, p185
      and cell differentiation and prognosis in rhabdomyosarcoma].
AB  - OBJECTIVE: To study the correlation between expression of oncogene protein
      products p53, P21, p185 and histological type, cell differentiation and prognosis
      in rhabdomyosarcoma (RMS). METHODS: 41 RMS cases which had follow-up material
      were selected for this study. Expression of protein products of oncogene p53, p21
      and p185 were synchronously detected and compared by immunohistochemical ABC
      method. RESULTS: The positive rates for p53, p21 ras and P185 c-erbB-2 were 72%,
      68% and 60% respectively. Positive expression did not relate to age, sex or RMS
      histological type, but related to the degree of RMS differentiation. The positive
      rate of p53 ad p21 ras in well differentiated cases were 42.9% and 28.6% while
      that of the poorly differentiated group was 85% and 80% respectively (P < 0.05).
      The psoitive rate of p53 in the RMS group with metastasis was 86.6%,
      significantly higher than that of the non-metastasized group, which was 66.7% (P
      < 0.05). There was a significant difference between those with one year survival,
      whose p52 positive rate was 86.7% and those who survived for more than 3 years,
      whose p53 positive rate was 47.1% (P < 0.05). CONCLUSION: The results suggest
      that the irregular expressions of p53 and p21 were related to tumor
      differentiation and the degree of malignancy. p53 positivity may indicate a poor
      prognosis.

PMID- 10072849
TI  - [Distribution of 70kDa heat shock protein in rabbit brains after heat stress and
      heat stroke].
AB  - OBJECTIVE: Evaluation of the relationship between the induction of 70kDa heat
      shock protein in rabbit brains and heat stress. METHODS: HSP70 was detected using
      monoclonal antibody by ABC method in rabbit hypothalamus, hippocampus and
      cerberal cortex. RESULTS: Intense HSP70 staining was displayed in rabbit brains
      of the heat stroke group (rectal temperature 43 degrees C to death). Positive
      cells were distributed mainly in the CA1, CA2 regions of the hippocampus;
      granular cell layer I and pyramidal layer (II) of the cerebral cortex; and the
      periventricular area of hypothalamus. HSP70-psoitive substances were localized in
      the cytoplasm and neuronal processes, a few neurons exhibited dark staining
      nucle. Hosever, the rabbit brains of the general heat stress group (rectal
      temperature 42.0 degrees C, 30 minutes) had much weaker staining. CONCLUSION:
      Hyperthermia causes neuronal expression of HSP70, particularly under strong heat
      stress, and may be sustained till death.

PMID- 10072850
TI  - [New trend of the researches on gastrointestinal cancer].

PMID- 10072851
TI  - [A study on the loss of heterozygosity at 17p13.3 and abnormal expression of p53
      protein in gastric carcinoma].
AB  - OBJECTIVE: To evaluate the role of 17p13.3 loss and abnormal expression of p53 in
      the development and progress of gastric carcinoma. METHODS: The loss of
      heterozygosity (LOH) at 17p13.3 and abnormal expression of p53 gene were examined
      with PCR-RFLP and immunohistochemical methods in 51 surgical specimens of gastric
      carcinoma. RESULTS: LOH at 17p13.3 was detected in 16/31 cases (51.6%) and
      positive staining for p53 protein was found in 19/51 cases (37.3%). No
      significant correlation was found between LOH at 17p13.3 and abnormal expression
      of p53 or between these two events in any clinicopathological parameters. LOH was
      found in one cases of early gastric cancer. CONCLUSIONS: These results suggest
      that LOH at 17p and abnormal expression of p53 protein are frequently found in
      gastric carcinoma and may play an important role in the carcinogenesis and
      progress of both intestinal and gastric types of gastric cancer.

PMID- 10072852
TI  - [Apoptosis and expression of its regulating genes in adenoma and adenocarcinoma
      of large intestine].
AB  - OBJECTIVE: To investigate the effects of apoptosis and its regulating genes in
      different stages of malignant transformation of large intestine epithelium in
      colorectal adenoma and adenocarcinoma. METHODS: The density and distribution of
      the apoptotic cells and the positive expression of p53 and bcl-2 oncoprotein were
      observed in situ in 32 villous adenomas and 33 papillary adenocarcinomas of the
      large intestine, using DNA nick end labelling technique and immunohistochemical
      staining for p53 and bcl-2 oncoprotein. 15 nontumor mucosa were used as controls.
      RESULTS: The density of apoptotic cells in adenoma and adenocarcinoma was
      significantly higher than that in nontumor mucosa (P < 0.01), and their density
      in adenoma was higher than in adenocarcinoma (P < 0.01). The positive rate and
      staining intensity of p53 and bcl-2 oncoprotein in adenoma and adenocarcinoma
      were significantly higher than in non tumor mucosa (P < 0.01), their staining
      intensity in adenocarcinoma was higher than that in adenoma (P < 0.01). In
      adenoma, the density of apoptotic cells in the bcl-2 oncoprotein positive group
      was higher than that in the bcl-2 oncoprotein negative group (P < 0.01).
      CONCLUSION: The abnormal regulation of apoptosis may play an important role in
      the pathogenesis of large intestine carcinoma. The bcl-2 oncoprotein can inhibit
      apoptosis in adenoma and adenocarcinoma. However, mutational p53 oncoprotein may
      likely block apoptosis in adenocarcinoma.

PMID- 10072853
TI  - [An immunohistochemical double labelling study on type IV collagenase and
      basement membrane in human colonic carcinoma].
AB  - OBJECTIVE: To investigate the relationship between type IV collagenase and
      basement membrane (BM) and the relationship between type IV collagenase and p21
      expression. METHODS: Immunohistochemical double labelling technique was used to
      study paraffin embedded sections of 86 cases of colon carcinoma. RESULTS: The
      positive rate of type IV collagenase was 83.72% in carcinoma cases and 10% in
      normal colorectal mucosa (P < 0.01). Intact BM was seen in normal colorectal
      mucosa while BM was disrupted and fragmentary in carcinoma cases. A close
      positive correlation was also found between the expression of type IV collagenase
      and p21 in colonic carcinoma (r = 0.974, P < 0.01). CONCLUSIONS: The results
      suggest that type IV collagenase plays an important role in the destruction of BM
      and invasion by colonic carcinoma.

PMID- 10072854
TI  - [A study on histogenesis of gastrointestinal stromal tumors].
AB  - OBJECTIVE: The purpose of this study was to consider the histogenesis of
      gastrointestinal stromal tumors (GIST). METHOD: 36 cases of GIST were studied by
      light microscopy, histochemical and immunohistochemical techniques. RESULTS: In
      15 cases of small intestine spindle cell tumors, various sized eosinophilic
      globules were observed between the tumor cells and were designated as skeinoid
      fibers, which stained blue with Masson's trichrome and strongly PAS-positive. The
      positive rate by immunohistochemical methods for S-100 protein and desmin were
      44.44% and 8.33% respectively. The immunoexpression of tumor cells was unrelated
      to their differentiation. CONCLUSION: Complex immunophenotypes of GIST suggest
      primitive mesenchymal origin, and small intestine stromal tumors (SIST) are
      mostly neurogenic which may have been derived from neurilemmal cells or
      autonomous nerve tissue of the small intestine.

PMID- 10072855
TI  - [Inhibition of cell growth and target gene expression of human pancreatic
      carcinoma cells by modified antisense oligodeoxynucleotide].
AB  - OBJECTIVE: To investigate the inhibitory effects of modified antisense
      oligodeoxynucleotide on cell growth, 3H-TdR incorporation rate and target gene
      expressions of human pancreatic carcinoma cells as a comparison with the
      effectiveness of nonmodified antisense oligodeoxynucleotide (ASODN) resported
      previously. METHODS: Synthesized modified antigsense oligodeoxynucleotides
      (antisense phosphorothioate oligodeoxynucleotides, ASPODN) complementary to the
      cap regions of c-myc and Ki-ras genes were used to treat PC-2 and PC-3 human
      pancreatic carcinoma cell line cells with multiple small (10 micrograms) doses or
      one single dose (15 micrograms). After treatment, cell growth rates and 3H-TdR
      incorporation rates were estimated, and the concurrent oncogene expressions were
      studied by adopting RT-PCR technique. RESULTS: After multiple ASPODN exposures,
      the cell growth rates and 3H-TdR incorporation rates were significantly
      inhibited, the inhibition was maintained for more than two weeks. On the 14th
      day, the cell growth rates of the ASPODN groups were reduced to 38%-43% of that
      of the controls, and the 3H-TdR incorporation rates were 18%-33% of that of the
      controls, there were also marked inhibition or down-regulation of target genes (c
      myc and Ki-ras) expressions. After the 15 micrograms single dose treatment, the
      inhibition of cell growth, 3H-TdR incorporation and target gene expressions
      lasted for 4 days. CONCLUSIONS: The results of this study confirm the fact that
      ASPODN exerts a more strong inhibitory effect on pancreatic carcinoma cells than
      the non-modified ASODN.

PMID- 10072856
TI  - [Mutation and methylation of CDKN2 gene in human head and neck carcinomas].
AB  - OBJECTIVE: To study mutations of CDKN2 gene in human head and neck carcinomas
      (HNC) and to elucidate the role of this gene in tumorigenesis. METHODS: PCR-SSCP
      and sequencing techniques were used to detect mutations in fresh specimens from
      36 HNC cases. Specimens from 20 cases were further analysed for methlyation
      status of the CpG islands in the first exon of the gene using restriction enzyme
      digestion plus Southern blotting analysis. RESULTS: CDKN2 gene mutations were
      detected in 4 HNC cases of which 2 were missense mutation and the other 2 were
      frameshift mutation. Methylation status analysis revealed that 8 out of 20 HNC
      cases had de novo methylation of CpG island within the first exon of CDKN2 gene.
      CONCLUSION: The results shown here suggest that in addition to gene mutation and
      deletion, de novo methylation of the CpG island may be a frequent event in human
      carcinogenesis.

PMID- 10072857
TI  - [Epstein-Barr virus infection and the expression of bcl-2 proto-oncogene in
      Hodgkin's disease].
AB  - OBJECTIVE: To investigate the relationship between Epstein-Barr virus (EBV) and
      bcl-2 gene. METHODS: Sixty-four paraffin-embeded cases of Hodgkin's disease (HD)
      were studied. Immunohistochemistry was performed by using monoclonal antibody to
      latent membrane protein 1 (LMP-1) and bcl-2. In situ hybridization for EBV
      encoded small mRNA-EBER on 41 cases. Double staining combined in situ
      hybridization and immunohistochemistry was performed for dual labelling of EBER
      and bcl-2 in seven cases. RESULTS: The positive rates of LMP-1 and EBER were 39%
      and 44%. All cases which were EBER positive, also express LMP-1. The positive
      rate of bcl-2 protein was 23%. Only seven of these cases were also LMP-1
      positive. CONCLUSION: All the results suggest that the bcl-2 expression in the R
      S cells in this series did not correlate with EBV-positivity.

PMID- 10072858
TI  - [The relationship between prognosis, metastasis and microvessel quantity in
      invasive breast carcinoma].
AB  - OBJECTIVE: To determine the prognostic value and relationship of microvessel
      quantity (MVQ) with PCNA, c-erbB-2, nm23-H1 and Cathepsin D in invasive breast
      carcinoma. METHODS: Immunohistochemical techniques (LSAB) were used to detect the
      expression of PCNA, c-erbB-2, nm23-H1, Cathepsin D and MVQ in 76 cases of
      invasive breast carcinoma. RESULTS: The mean of MVQ was 57.82 +/- 22.22 in 76
      cases of invasive breast carcinoma. The expression of Cathepsin D (cancer cells),
      c-erbB-2 and node positive were not related to MVQ. MVQ was positively correlated
      to expression of Cathepsin D (stroma cells), PCNA and distant metastasis (10
      years), but negatively correlated to 5 year survival. CONCLUSION: MVQ was
      significantly correlated to distant metastasis and survival period in invasive
      breast carcinoma. MVQ may be an independant prognostic indicator.

PMID- 10072859
TI  - [Expression of human papillomavirus 16, 18 E6 protein of cervical squamous cell
      carcinoma].
AB  - OBJECTIVE: To investigate the expression of human papillomavirus (HPV) 16, 18 E6
      protein of cervical squamous cell carcinoma and to assess the practical value of
      HPV 16, 18 E6 antibody. METHODS: Immunohistochemistry SP method was used to
      examine HPV 16, 18 E6 protein expression in 40 cases of squamous cell carcinoma
      of uterine cerivx, 30 cases of chronic cervicitis and 30 cases of normal cervical
      epidermal tissue. RESULTS: 27/40 carcinoma cases and 1/30 chronic cervicitis
      showed positive staining. None of the normal epithelium specimens gave positive
      results. The difference between malignant and benign groups was significant.
      CONCLUSION: A close relation between high risk HPV 16, 18 E6 antibody could be a
      good indicator for HPV 16, 18 infection and early diagnosis of cervical
      carcinoma.

PMID- 10072860
TI  - [Advances in clinicopathological study on gastric endocrine neoplasms].

PMID- 10072861
TI  - [Current topics in the renal pathology researches].

PMID- 10072862
TI  - [Effect of platelet derived growth factor on the growth of human glomerular
      mesangial cells in vitro].
AB  - OBJECTIVE: To study the effect of plateletderived growth factor (PDGF) on the
      growth of human glomerular mesangial cells (MsC) in vitro. METHODS:
      Immunohistochemistry for the detection of BrdU positive cells; [3H] proline
      incorporation for the bioactive assay of total amount of collagen; and Northern
      blot analysis for the determination of fibronectin (FN) alpha 1 (IV) collagen and
      c-myc mRNA expression. RESULTS: The cell labelling index (LI) of BrdU
      incorporation in the PDGF group is 34.5% higher than that in the normal group,
      which was 19.5% (P < 0.01), The total amount of collagen secreted by MsC within
      cells and outside of cells in the PDGF group were 2.69 +/- 0.60% and 3.87 +/-
      0.65% respectively, much higher than that of the normal group, which were 1.25 +/
      0.50% and 1.61 +/- 0.51% respectively (P < 0.01). Northern blot analysis
      revealed an increase of FN, Col IV, c-myc mRNA levels in the PDGF group.
      CONCLUSION: PDGF can stimulate cell proliferation, synthesis of collagen and
      enhance FN, Col IV, c-myc mRNA expression. It is possible that PDGF may play an
      important role in the development and progression of glomerulopathy.

PMID- 10072863
TI  - [The relationship between tumor necrosis factor and glomerular mesangial cells].
AB  - OBJECTIVE: To study the autocrine function of tumor necrosis factor (TNF) in
      glomerular mesangial cells (MC) and the action of TNF on MC. METHODS: Cultured
      rat and human MC were studied by RT-PCR, in situ hybridization and
      immunohistochemical methods. RESULTS: The expression of both TNF and TNF receptor
      mRNA and protein synthesis in MC were manifested. CONCLUSION: (1) MC is the
      target cell for TNF, MC have specific cell surface receptor to TNF. (2) TNF acts
      on MC through both autocrine and paracrine mechanism.

PMID- 10072864
TI  - [Microsatellite instability in nephroblastoma and its relationship to
      clinicopathological variables].
AB  - OBJECTIVE: To study the relationship between microsatellite instability (MSI) and
      clinicopathological variables in nephroblastoma. METHODS: 2 microsatellite repeat
      sequences AR (chromosome X), UT762(chromosome 21) were examined in normal and
      tumor pairs from 50 nephroblastoma patients by PCR and denatured polyacrylamide
      gel electrophoresis. RESULTS: The MSI positive for AR and UT loci were 14/50 and
      10/50 respectively in nephroblastoma. MSI positive for both AR and UT occurred in
      2 cases. According to NTWS-III categorization, stage I & II belong to early stage
      and stage III & IV belong to late stage, the MSI for this series were 16/38 and
      6/12 for early and late stages. According to the NWTI-II categorization, the MSI
      of this series for favorable and non-favorable histology were 71% and 33%
      respectively. CONCLUSIONS: Analysis of MSI may have some significance in
      discriminating the malignant status of nephroblastoma.

PMID- 10072865
TI  - [Expression of P21, p53 and proliferating cell nuclear antigen in human bladder
      cancer].
AB  - OBJECTIVE: To study the expression of cancer gene product and anti-cancer gene
      product in the same bladder cancer. METHODS: Immunohistochemical staining was
      used to determine the expression of P21, p53 and proliferating cell nuclear
      antigen (PCNA) in 5 normal bladder tissues and 58 bladder cancers. RESULTS: No
      P21, p53 and PCNA were expressed in the 5 normal bladder tissue samples. The
      positive incidence of P21, p53 and PCAN expression in the bladder cancers were
      62.1%, 55.2% and 58.6% respectively. p53 and PCNA were located in cell nuclei and
      P21 located on the cell membrane in bladder cancer. The expression of P21, p53
      and PCNA correlated to the stage, clinical grade and patient survival rates of
      this tumor. CONCLUSION: These results suggest that P21, p53 and PCNA
      immunolabelling may be used to determine the prognosis of bladder cancer
      patients.

PMID- 10072866
TI  - [The inhibitory effect of antisense interleukin-6 on the growth of human lung
      carcinoma cells in vivo].
AB  - OBJECTIVE: Interleukin-6 (IL-6) has previously been implicated as a potential
      positive autocrine regulator of a human lung carcinoma cell lince PG. The purpose
      of the present study is to further evaluate the role of IL-6 in PG cells in vivo.
      METHODS: An antisense expression vector for IL-6 was constructed and introduced
      into PG cells. Antisense mRNA of IL-6 was detected by RNA-RNA dot blotting
      analysis. The production of bioactive IL-6 was measured by bioassay method. To
      determine the effect of antisense IL-6 cDNA on tumorigenicity, PG cells were
      inoculated subcutaneously into nude mice. RESULTS: Four transfectants, PGTAS1,
      PGTAS6, PGTAS8, PGTAS9, could express IL-6 antisense mRNA and secret decreased
      bioactive IL-6. The growth rate of 4 transfectants revealed was reduced in vitro.
      Comparing with the mice injected with the control PGTneo cells, the latent period
      of the mice inoculated with PGTAS6, PGTAS8, PGTAS9 cells was significantly
      increased, and the growth rate of the tumors was obviously decreased. The tumor
      size was markedly smaller. There was a negative correlation between the growth
      inhibiting effect of IL-6 antisense gene and the amount of IL-6 secretion.
      CONCLUSION: These results indicate that IL-6 can function as an autocrine
      stimulator for PG cells in vivo as well as in vitro.

PMID- 10072867
TI  - [A cytogenic study on colorectal carcinoma].
AB  - OBJECTIVE: To study the cytogenesis of colorectal carcinoma and to look for
      colorectal carcinoma related chromosomal fragility sites which could facilitate
      screening of high risk colorectal carcinoma patients. METHODS: 20 cases of
      surgically resected colorectal carcinomas and 4 cell lines were analysed
      cytogenetically. RESULTS: Most of the tumor cells were heteroploid, the
      chromosome number was predominately hypodiploid. Karyotypic analysis demonstrated
      an increase of chromosome 13, and loss of chromosome 17 and chromosome 1 appeared
      frequently. The most frequently found structural abnormalities in colorectal
      carcinoma were breakpoint 1q21 and 1p13. Highly non-random cancer chromosome
      breakpoints and fragile sites were compared with the oncogene locus and found
      that their locus or neighboring locus was 1q21. CONCLUSION: The results suggest
      that breakpoint 1q21 may be related to tumorgenesis and may be useful in
      screening and preventing colorectal carcinoma.

PMID- 10072868
TI  - [Association of epstein-barr virus with lymphoepithelioma-like carcinoma of the
      lung].
AB  - OBJECTIVE: To study the relationship between pulmonary lymphoepithelima-like
      carcinoma (LELC) and Epstein-Barr virus (EBV). METHODS: 30 cases of LELC and 19
      cases of non LELC pulmonary pulmonary specimens were studied by in situ
      hybridization and immunohistochemistry techniques to detect EB virus small RNA
      (EBERs), latent menbrane protein-1 (LMP-1) and virus capsid antigen (VCA).
      RESULTS: The detection rates for EBER, LMP-1 and VCA were 93.3% (28/30), 53.3%
      (16/30) and 23.3% (7/30) respectively. LMP-1 positive carcinoma cells were not
      found in the 19 non-LELC specimens, which were used as the controls. CONCLUSION:
      Pulmonary LELC is closely associated with latent EBV infection and may be an
      important factor involved in the development and progression of LELC. In
      addition, EBV lytic gene products may sometimes be found in a small portion of
      LELC cells.

PMID- 10072869
TI  - [The significance of detecting EB virus and its products in benign and malignant
      lymphoepithelial lesions of the salivary glands].
AB  - OBJECTIVE: To study the relationship between EB virus and benign malignant
      lymphoepithelial Lesions (ELEL) and malignant lymphoepithelial lesions (MLEL).
      METHODS: In situ hybridization, polymeras Chain reaction (PCR) and
      immunohistochemical methods were used to detect EBV DNA, EBER1 and latent
      membrane protein 1 (LMP1) on paraffin embedded tissues of 18 MLEL cases and 14
      BLEL cases. RESULTS: (1) Positive rates for Bam H1 W fragmet by PCR and EBER1 by
      in situ hybridization in 18 cases of MLEL were both 100%. Positive rates of EBV
      DNA by PCR and EBER1 by in situ hybridization in 14 cases of BLEL were both zero
      percent. (2) LMP1 expression was detected in 77.8% (14/18) of MLEL, EBNA2 was
      examined in 9 cases of MLEL and no expression was found. (3) Among the
      infiltrating lymphocytes studied by immunohistochemistry, T cells predominated
      over B cells in MLEL, B cells predominated over T cells in BLEL. (4) Of the 216
      cases of salivary gland cancer, 37 cases could satisfy the criteria for MLEL. The
      incidence of MLEL in this group was 17.13% (37/216). CONCLUSION: Our results
      suggest that EBV infection may have some relationship with the genesis of MLEL.

PMID- 10072870
TI  - [Mutation and expression of p53 gene in nasopharyngeal carcinoma, cervical
      carcinoma and lung cancer].
AB  - OBJECTIVE: To investigate the mutation and expression of p53 tumor suppressor
      gene in nasopharyngeal carcinoma (NPC), cervical carcinoma and lung cancer.
      METHODS: 24 NPCs, 9 cervical carcinomas and 10 lung cancers were examined by
      immunohistochemical and PCR-SSCP techniques. RESULTS: 23/24 (90.1%) NPCs, 6/9
      (66.7%) cervical carcinomas and 9/10 (90.0%) lung cancers showed p53
      overexpression. No NPC or cervical carcinoma had p53 mutations in exons 5-8 of
      the gene, whereas mutations were found in 5 lung cancers, one in exon 8 and four
      in exon 5. All five cases showed p53 overexpression. CONCLUSIONS: Overexpression
      of p53 exists in NPC, cervical carcinoma and lung cancer. It is related to gene
      mutation in lung cancer, but not in NPC or cervical carcinoma. The DNA tumor
      viruses may be involved in the overexpression of p53 in NPC and cervical
      carcinoma.

PMID- 10072871
TI  - [Advances in the study of the role of vascular endothelial growth factor and its
      receptor in tumor angiogenesis and its relation with anti-angiogenesis effect].

PMID- 10072872
TI  - [Expression and detection of integrin alpha 5 beta 1, fibronectin and its
      fragment in patients with hepatocellular carcinoma].
AB  - OBJECTIVE: To study the relationship between the expression of integrin alpha 5
      beta 1, fibronectin (FN) and its fragment (malignant disease-associated DNA
      binding protein 2 MAD2) and the biologic behavior of human hepatocellular
      carcinoma HCC) as well as the significance of MAD2 detection in plasma. METHODS:
      Integrin alpha 5 beta 1, FN and MAD2 were localized by immunohistochemical
      methods and quantified by image analysis in tumor and peripheral liver tissues
      from 40 HCC cases. The concentration of FN and MAD2 in the plasma samples from
      30/40 cases were examined using the ELISA method. RESULTS: The expression of
      integrin alpha 5 beta 1, FN and MAD2 in well differentiated HCC were not
      significantly different from that of normal tissues, while they were markedly
      decreased or undetectable in mode rately and poorly differentiated HCC. Decreased
      expression of integrin alpha 5 beta 1 and FN at sites where HCC invaded the
      connective tissue and enhanced expression on the HCC cells around cancerous
      emboli were also noted. The mean concentration of plasma MAD2 in patients with
      HCC were significantly increased when compared to those with chronic liver
      disease and normal subjects. CONCLUSIONS: The changes in integrin alpha 5 beta 1
      and FN expression may be associated with HCC differentiation, invasion and
      metastasis. The detection of plasma MAD2 in patients with HCC may have clinical
      significance.

PMID- 10072873
TI  - [Clinicopathological study on 3,160 cases of liver tumors].
AB  - OBJECTIVE: To study the developmental and clinicopathological characteristics of
      liver tumors in China. METHODS: Routine methods were utilized to analyse the
      composition and clinicopathological features of 3,160 cases of liver tumors which
      were surgically resected during a period of 14 years. RESULTS: 25 types of liver
      tumors arising from three germinal layers were studied. Tumor-like lesions, 4
      types, 112 cases (3.5%); benign tumors, 10 types, 499 cases (15.8%); malignant
      tumors, 11 types, 2,549 cases (80.7%). Of the three groups, the most common being
      inflammatory pseudotumors, accounting for 73.2% of tumor-like lesions, cavernous
      hemangioma, accounting for 74.3% of benign tumors and hepatocellular carcinoma,
      accounting for 96.8% of malignant tumors respectively. The association of
      cirrhosis in small hepatocellular carcinoma (< 3 cm) was as high as 83.2%.
      CONCLUSION: A close relationship between HBV, liver cirrhosis and hepatocellular
      carcinoma exists.

PMID- 10072874
TI  - [A study on type I, III and IV collagen production in CCl4 induced rat liver
      fibrosis].
AB  - OBJECTIVE: To study the dynamic changes of alpha 1 (I), alpha 1 (III) and alpha I
      (IV) procollagen mRNA and collagen-producing cells during CCl4 induced SD rat
      liver fibrogenesis (20 weeks). METHODS: The investigations were performed using
      Northern blot analysis, in situ hybridization and immunohistochemical techniques.
      RESULTS: The increased expression of alpha 1 (III) procollagen mRNA during
      fibrogenesis by Northern blot analysis was the most predominant among the three
      mRNAs studied. However, the increase of alpha 1 (IV) procollagen mRNA expression
      occurred earlier, while the expression of alpha 1 (I) mRNA did not increase until
      the middle stage of the experiment. Desmin positive and/or smooth muscle actin
      positive Ito cells and myofibroblasts (MFs) in and around the necrotic areas
      expressed alpha 1 (I), alpha 1 (III) and alpha 1 (IV) procollagen mRNA signals
      detected by in situ hybridization during the early stage of the experiment. All
      the three procollagen mRNAs were mostly localized in fibroblasts (Fbs) and MFs in
      the septa during the mid and late stages of fibrosis. CONCLUSIONS: Fbs and MFs
      were considered as important Col I, Col III and Col IV producing cells in liver
      fibrosis. Sinusoid endothelia were involved in Col IV synthesis in the fibrotic
      liver.

PMID- 10072875
TI  - [Uptake of Escherichia coli lipopolysaccharide and expression of tumor necrosis
      factor-alpha-mRNA by isolated rat intrahepatic bile duct epithelial cells].
AB  - OBJECTIVE: To study the uptake of E. coli lipopolysaccharide (LPS) and expression
      of tumor necrosis factor-alpha-mRNA in isolated intrahepatic bile duct epithelial
      cells. METHODS: Fluorescent immunohistochemical and in situ hybridization
      techniques and observations with a confocal laser scanning microscope. RESULTS:
      Positive reactions to LPS were found in the cytoplasm of isolated intrahepatic
      bile duct epithelial cells after incubation with S type LPS (S-LPS) for 15
      minutes, and the FITC fluorescent intensity against LPS was significantly higher
      than that of controls. After incubation with S-LPS for 3 hours, FITC fluorescent
      intensities to the expression of tumor necrosis factor (TNF)-alpha-mRNA by
      flurescent in situ hybridization in the cytoplasm and nuclei of cultured bile
      duct epithelial cells were significantly higher than that of controls. The
      increase of FITC fluorescent intensity to TNF-alpha-mRNA expression showed a peak
      at 6 hours after incubation and at various time points after incubation with LPS,
      the increase of fluorescent intensities in the cytoplasm were much higher than
      that in the nuclei. CONCLUSION: It is suggested that LPS could act on and enter
      into isolated intrahepatic bile duct epithelial cells and stimulate the
      expression of TNF-alpha-mRNA.

PMID- 10072876
TI  - [Expression of ICAM-1 mRNA in HCC using in situ hybridization technique].
AB  - OBJECTIVE: To study the relationship between the intercellular adhesion molecule
      1 (ICAM-1) mRNA expression of hepatocellular carcinoma (HCC) and its invasion and
      metastasis. METHODS: 34 cases of HCC and their pericarcinomatous tissues were
      studied on cryostat sections by in situ hybridization to investigate ICAM-1 mRNA
      expression. RESULTS: The ICAM-1 mRNA expression was stronger in the carcinomatous
      tissues of 19/21 invasive cases than that in the pericarcinomatous tissues, while
      in the 13 non-invasive cases, only 4 exhibited weak ICAM-1 mRNA expression.
      CONCLUSION: ICAM-1 mRNA expression may correlate with increased risk of invasion
      and metastasis of HCC.

PMID- 10072877
TI  - [A comparative study on p53 gene mutation in primary human Dukes C colon cancer
      with that in matched lymph node metastasis].
AB  - OBJECTIVE: To study the relationship between metastasis of colon cancer and the
      mutation of p53 gene. METHODS: PCR-SSCP was used to analyse exon 5-9 of the p53
      gene in 73 cases of Dukes C human primary cancer and 40 cases of matched lymph
      node metastasis. RESULTS: Mutations were identified in 27 of 73 primary cancers
      (37%) and 19 of 40 lymph node metastasis (47.5%) with the overall incidence of
      p53 mutation being 44%. In 21 of 40 cases in which both primary and metastatic
      cancers were analysed by SSCP, we found no p53 mutations in both lesions. While
      the same exon and exactly the same mutated band pattern could be seen both in
      primary and metastatic cancers in another 12 cases (30%). In addition, the
      agreement of p53 mutation status in primary cancer to the lymph node metastases
      was lost in the remaining 7 cases (17.5%). All of the 7 cases were confirmed to
      have base substitution mutations by DNA direct sequencing. In 5 of 7 individuals,
      the point mutations were detected only in lymph node metastases but not in the
      primary cancers and in 2 of 7 cases, two exons were found to have mutations in
      lymph node metastases while only one or no mutation was identified in the primary
      cancers. CONCLUSION: Most p53 mutations occurred before metastasis and p53
      mutations persist throughout the final stage of the progression and metastasis in
      colon cancer. Furthermore, the metastasis of colon cancer is accompanied by the
      emergence of new mutation in p53 gene or metastasis is selected against the p53
      mutation, which suggests that the mutations in p53 gene may be related to the
      metastasis of colon cancer.

PMID- 10072878
TI  - [Proliferative activities, oncoprotein expression and their significance in human
      gliomas].
AB  - OBJECTIVE: To explore the relationship between the proliferative activities,
      oncoprotein expression, cell differentiation and prognosis of gliomas. METHODS:
      Immunohistochemistry and image analysis were used to study the expression of
      proliferating cell nuclear antigen (PCNA) and several oncoproteins both
      qualitatively and quantitatively in 124 brain gliomas. RESULTS: It was found that
      the intensities of PCNA reaction were significantly related to both the grade and
      prognosis of gliomas. Overexpression of c-erbB-2 protein was slightly stronger in
      well than in poorly-differenciated gliomas. Moreover, the reactions in patients
      who survived over 5 years were stronger than in those under 5 years. EGF (40.0%),
      EGFR (91.4%) and p21ras (53.3%) expression levels were related to neigher the
      grading nor prognosis of this tumor. The positive ratios of the three antibodies
      to p53 protein were higher in grades II-IV than in grade I gliomas. The intensity
      of p53 reaction was correlated to that of PCNA. CONCLUSION: It is suggested that
      the aberration of c-erbB-2, p21ras, EGF and EGFR might be the early events in the
      initiation and progression of gliomas, whereas p53 is involved in all stages of
      these tumors. PCNA could reflect the degree of malignancy to a certain extent.

PMID- 10072879
TI  - [Differential expression and response of growth factors in metastatic variants of
      human pulmonary giant cell carcinoma cell line].
AB  - OBJECTIVE: To study the difference in expression and response of certain growth
      factors between the two metastatic variants PGbE1 and PGLH7 of human pulmonary
      giant cell carcinoma, and the action of these growth factors on the metastasis of
      tumor cells. METHODS: RT-PCT was conducted to detect the expression of TGF alpha,
      TGF beta 1, IL-6, IL-8, bFGF and ANG, and the expression of receptors EGFR, IL-6R
      and IL-8R; 3H-TdR incorporation assay was used to determine the effects of
      recombinant TGF alpha, TGF beta 1 and IL-6 on the proliferation of the two cells.
      RESULTS: TGF alpha, EGFR, IL-6 and IL-6R were expressed at a higher level in
      PGbE1 cells than in PGLH7 cells. No significant differences were found in the
      expression of TGF beta 1, bFGF, IL-8, IL-8R and ANG between the two cells.
      Recombinant TGF alpha and IL-6 stimulated the proliferation of both cells, while
      TGF beta 1 had dual effects. CONCLUSION: TGF alpha, TGF beta 1, bFGF, IL-6, IL-8
      and ANG may be involved in the autocrine regulation of the growth and
      proliferation of pulmonary giant cell carcinoma, TGF alpha and IL-6 may play an
      important role in the metastasis of the tumor cells.

PMID- 10072880
TI  - [Effects of dexamethasone on cAMP production induced by prostaglandin E2 in
      aortic smooth muscle cells].
AB  - OBJECTIVE: To study the effects of dexamethasone on cAMP production induced by
      prostaglandin E2 (PGE2) in cultured rabbit aortic smooth muscle cells. METHODS:
      cAMP concentration was determined by protein-competition-contact assay. RESULTS:
      Dexamethasone significantly inhibited cAMP accumulation induced by PGE2 in a dose
      dependent manner in the range between 10 pmol/L and 10 nmol/L. The inhibitory
      effect grew stronger as the time of pretreatment extended. Adenylate cyclase
      activity induced by PGE2 was significantly reduced in the cells pretreated with
      dexamethasone. CONCLUSION: The results strongly suggest that dexamethasone
      inhibits cAMP production induced by PGE2 in cultured aortic smooth muscle cells
      and the inhibitory effect is exerted at the level of adenylate cyclase. In
      addition, the inhibitory effect of PGE2 on cultured smooth muscle cell
      proliferation was resisted by dexamethasone, anyhow no direct enhancing effect on
      cell proliferation by dexamethasone was detected.

PMID- 10072881
TI  - [Clinicopathological study on 15 cases of pilomatrix carcinoma].
AB  - OBJECTIVE: To analyse the pathomorphology and the clinical biological behavior of
      pilomatrix carcinoma as well as to clarify the main points of diagnosis and
      differential diagnosis. METHODS: A review of the clinicopathological,
      histochemical and immunohistochemical features of 15 pilomatrix carcinomas a well
      as their clinical data was made. RESULTS: Of the 15 cases, 6 were male and 9
      female, aged 11 to 83 (mean age 46 years). The tumor diameter varied from 1.2 cm
      to 8.0 cm (mean 3.5 cm). Histologically, pilomatrix carcinomas are characterized
      by sheets and islands of proliferating atypical baseloid cells with an
      infiltrating border. Transition to squamous, clear and ghost cell are often
      observed. The trichohyalin granules and tricholin-like acidophilic bodies are
      seen in tumor cells. Follow-up on 13 cases revealed local recurrence in 7 cases
      with multiple recurrence in 2 cases. One died of liver metastasis and one died of
      extensive local spread of the tumor. CONCLUSION: Pilomatrix carcinoma is a
      malignant tumor which usually recurs. Better curative results are obtained by
      wide excision.

PMID- 10072882
TI  - [Severe combined immunodefficiency disease, 4 autopsy case reports].
AB  - OBJECTIVE: To study the pathological changes of severe combined immunodefficiency
      disease (SCID). METHODS: 4 cases with SCID proven by autopsy examination.
      RESULTS: All patients were male with an average age of 5 moths. The major
      clinical manifestations included severe repeated infection with bacteria, virus,
      fungi and pneumocystis carinii. Autopsy examination revealed hypoplasia of
      thymus, spleen and lymph nodes. 1 case died from pneumocystis carinii pneumonia
      and BCG vaccine disease, 2 cases died of severe general infection and 1 case died
      from large cell lymphoma. CONCLUSIONS: The main diagnosis criteria for SCID are
      hypoplasia of both T and B lymphocytes, the pathologic changes of SCID are very
      complex.

PMID- 10072883
TI  - [The relation between EB virus and Burkitt's lymphoma].
AB  - OBJECTIVE: To study the relationship between Burkitt's lymphoma and Epstein-Barr
      (EB) virus. METHOD: Two cases of primary nasopharyngeal Burkitt's lymphoma in
      children were studies. Clinical features include nasal obstruction and dyspnea.
      The histology of Burkitt's lymphoma was confirmed by use of immunohistochemistry,
      in situ hybridization and double labelling techniques, the immunophenotype and EB
      virus locating sites were investigated. RESULTS: The EB positive cells are B
      cells and represent 60%-95% of the tumor cells. CONCLUSION: Nasopharyngeal
      primary Burkitt's lymphoma is associated with EB virus in Chinese.

PMID- 10072884
TI  - [Advances in the study of antigen retrieval in immunohistochemical techniques].

PMID- 10072885
TI  - Effect of melittin on ion transport across cell membranes.
AB  - Extensive work with melittin has shown that the venom has multiple effects,
      probably, as a result of its interaction with negatively changed phospholipids.
      It inhibits well known transport pumps such as the Na(+)-K(+)-ATPase and the H(+)
      K(+)-ATPase. Melittin increases the permeability of cell membranes to ions,
      particularly Na+ and indirectly Ca2+, because of the Na(+)-Ca(2+)-exchange. This
      effect results in marked morphological and functional changes, particularly in
      excitable tissues such as cardiac myocytes. In some other tissues, e.g., cornea,
      not only Na+ but Cl- permeability is also increased by melittin. Similar effects
      to melittin on H(+)-K(+)-ATPase have been found with the synthetic amphipathic
      polypeptide Trp-3.

PMID- 10072886
TI  - Comparison between huperzine A, tacrine, and E2020 on cholinergic transmission at
      mouse neuromuscular junction in vitro.
AB  - AIM: To compare the effects of huperzine A (Hup A), tacrine, and E2020 on
      cholinergic transmission at mouse neuromuscular junction in vitro. METHODS: The
      isolated mouse phrenic nerve-hemidiaphragm preparations were used with the
      conventional intracellular recording technique. The miniature end-plate
      potentials (MEPP), the mean quantal content of end-plate potentials (EPP), and
      the resting membrane potentials of muscle fiber were recorded. RESULTS: Hup A,
      tacrine, and E2020 at the concentration of 1.0 mumol.L-1 increased the amplitude,
      time-to-peak, and half-decay time of MEPP in the potencies of E2020 > Hup A >
      tacrine. Hup A did not significantly change the frequency of MEPP, the appearance
      of giant MEPP or slow MEPP, the resting membrane potentials, and the mean quantal
      content of EPP. CONCLUSION: Hup A is a selective and potent cholinesterase
      inhibitor, by which activity it facilitates the cholinergic transmission at mouse
      neuromuscular junction, and devoid of pre- and post-synaptic actions.

PMID- 10072887
TI  - Blockade of nitric oxide-induced relaxation of rabbit aorta by cysteine and
      homocysteine.
AB  - AIM: To examine the inhibition by L-cysteine (Cys) and L-homocysteine (HoCys) of
      NO-induced relaxation of aorta. METHODS: The tension of rabbit aortic rings in
      oxygenated Krebs' solution was recorded isometrically. RESULTS: Pretreatment of
      endothelium-denuded rings with Cys or HoCys inhibited the NO-induced increase in
      cGMP. The inhibitory effects of Cys or HoCys on relaxation responses to
      subsequent additions of NO 75 nmol.L-1 gradually diminished with time, which was
      consistent with the loss of the sulfhydryl concentration of Cys and HoCys.
      Superoxide dismutase (SOD) 35 kU.L-1 attenuated the inhibition by Cys and HoCys
      of NO-induced relaxation. Neither boiled SOD nor catalase 100 kU.L-1 antagonized
      the inhibitory effects of Cys. Preaddition of SOD 35 kU.L-1 inhibited the
      reduction of cytochrome C by Cys. Increasing concentrations of SOD from 35 to 350
      kU.L-1 intensified the cytochrome C reduction. Addition of xanthine 300 mumol.L-1
      plus xanthine oxidase 1 U.L-1 to the mixture of cytochrome C 60 mumol.L-1 and Cys
      100 mumol.L-1 produced an additional augmentation of SOD-inhibitable reduction of
      cytochrome C. The rate of the reduction of cytochrome C induced by HoCys 100
      mumol.L-1 was much slower than with Cys. Addition of NO reduced the SH
      concentrations of both the supernatant of aortic homogenate and Cys in Krebs'
      solution. CONCLUSION: The inhibition by the SH compounds of NO is mediated partly
      by the superoxide generated by the auto-oxidation of these compounds, and partly
      by a direct reaction of SH groups with NO.

PMID- 10072888
TI  - 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate actions on calcium dynamics
      in cultured vascular smooth muscle cells.
AB  - AIM: To study 8-(N,N-Diethylamino)n-octyl-3,4,5-trimethoxybenzoate (TMB), a
      potent Ca(2+)-antagonist, actions on cellular calcium dynamics in vascular smooth
      muscle cell (VSMC) cultures. METHODS: A7r5 VSMC were cultured with Fura-2
      measurements of intracellular Ca2+ concentration, [Ca2+]i. RESULTS: TMB reduced
      [Ca2+]i from control levels and blocked [Ca2+]i increase caused by norepinephrine
      (NE) and 2,5-di (t-butyl)-1,4-benzohydroquinone (BHQ). [Ca2+]i reduction by TMB
      was further enhanced by ryanodine. CONCLUSION: TMB is an effective agent for
      blocking the [Ca2+]i increase caused by NE and BHQ and for enhancing the [Ca2+]i
      reduction caused by ryanodine.

PMID- 10072889
TI  - Molecular cloning of cDNA encoding mitochondrial very-long-chain acyl-CoA
      dehydrogenase from bovine heart.
AB  - AIM: To clone the cDNA encoding an isoenzyme of mitochondrial very-long-chain
      acyl-CoA dehydrogenase (VLCAD) from bovine heart lambda gt11 and lambda gt10 cDNA
      libraries. METHODS: The clone was isolated with immunoscreening technique and
      validated by (1) the microsequences of the N-terminus and three internal
      proteolytic fragments from the purified enzyme; (2) identification of the acyl
      CoA dehydrogenase (AD) signature sequence; and (3) high homology of the deduced
      peptide sequences, as expected, with those of rat liver mitochondrial VLCAD.
      RESULTS: The cDNA (2203 bp) corresponds to a approximately 2.4-kb mRNA band from
      the same tissue source revealed by a Northern blotting. The deduced peptide
      sequence of 655 amino acids (70,537 Da) is composed of a 40-amino acid
      mitochondrial leader peptide moiety (4,346 Da) and a 615-amino acid peptide as a
      mature protein (66,191 Da). A comparison of the peptide sequences in the AD
      family shows the major diversity in their signal sequences, suggesting a
      structural basis for their different mitochondrial locations. The catalytic sites
      are all highly conserved among VLCAD. Ser-251 analogous to and Cys-215
      diversified to other family members. A pseudo-consensus sequence of leucine
      zipper was found in the C-terminal region from Leu-568 to Leu-589, implying a
      mechanism whereby the dimer of this protein is formed by zipping these leucine
      residues from the alpha-helixes of 2 monomers. CONCLUSION: The isolated cDNA
      clone encodes an isoenzyme of mitochondrial VLCAD in bovine heart.

PMID- 10072890
TI  - Effect of alpha-hederin on hepatic detoxifying systems in mice.
AB  - AIM: To examine whether alpha-hederin (Hed) modulates hepatic detoxifying systems
      as a means of hepatoprotection. METHODS: Mice were injected Hed 10 and 30
      mumol.kg-1 sc for 3 d, and liver cytosols were prepared 24 h after the last dose
      to study antioxidant enzymes and nonenzymatic defense components. RESULTS: Hed
      increased liver glutathione (GSH) content (20%), but had no effect on GSH
      peroxidase, GSH reductase, and GSH S-transferase. The activities of superoxide
      dismutase and quinone reductase were unaffected by Hed treatment. At the high
      dose of Hed, catalase activity was decreased by 20%. Hepatic content of
      metallothionein was dramatically increased (50-fold), along with elevations of
      hepatic Zn and Cu concentrations (25%-80%). Hed also increased ascorbic acid
      concentration (20%), but no effect on alpha-tocopherol in liver. CONCLUSION: Hed
      enhanced some nonenzymatic antioxidant components in liver, which play a partial
      role in Hed protection against hepatotoxicity produced by some chemicals.

PMID- 10072891
TI  - Binding conformers searching method for ligands according to the structures of
      their receptors and its application to thrombin inhibitors.
AB  - AIM: To develop a method of finding binding conformers for ligands according to
      the three-dimensional structures of their receptors. METHODS: Combining the
      systematic search method of ligand with the molecular docking approach of ligand
      fitting into its receptor, we developed a binding conformer searching method for
      ligands. RESULTS: The binding conformers of phosphonopeptidyl thrombin inhibitors
      were recognized. The binding (interaction) energies between these inhibitors and
      thrombin were calculated with molecular mechanical method. CONCLUSION: Both of
      the total binding energies and steric binding energies have good correlations
      with the inhibitory activities of these thrombin inhibitors, demonstrating that
      our approach is reasonable. It can also be used to explain the inhibition
      mechanism of thrombin interacting with these inhibitors.

PMID- 10072892
TI  - Pharmacokinetics of recombinant human granulocyte colony-stimulating factor in
      rabbits and mice.
AB  - AIM: To study the pharmacokinetics of recombinant human granulocyte colony
      stimulating factor (rhGCSF) in rabbits and mice. METHODS: 125I-rhGCSF was
      prepared by iodogen method and determined by size exclusive HPLC (SEHPLC).
      RESULTS: Concentration-time curves after i.v. 125I-rhGCSF in rabbits were best
      fitted with 2-compartment open model. The alpha and terminal elimination T1/2
      were 0.25-0.33 and 3.2-4.6 h, respectively. AUC increased with doses, and Cls and
      K10 were similar. Tpeak was 0.59 +/- 0.25 h after s.c., and elimination T1/2 was
      similar to that after i.v. The bioavailability after sc was 1.0. In mice the
      highest level was found in renal system, the next was bile-enteric system. Levels
      in lymph nodes, bone marrow, and spleen were approximately equal to or slightly
      lower than that in plasma, while the levels in brain, fat, and muscles were the
      lowest. About 68%-86% were recovered in urine and feces. CONCLUSION:
      Pharamcokinetics of 125I-rhGCSF in rabbits and mice provided a useful index for
      clinical trial.

PMID- 10072893
TI  - (-)-Stepholidine enhances K+ depolarization-induced activation of synaptosomal
      tyrosine 3-monooxygenase from rat striatum.
AB  - AIM: To study the mechanism of K+ depolarization-induced activation of
      synaptosomal tyrosine 3-monooxygenase (TM) in rat striatum and the effect of (-)
      stepholidine (SPD) on this activation. METHODS: The TM was assayed for DOPA by
      HPLC-ECD; the activities of Ca2+/calmodulin (CaM)-dependent protein kinase (PK
      II) and Ca2+/phosphoinositide-dependent protein kinase (PKC) were assayed using
      histidine as substrate. RESULTS: The incubation of striatal synaptosomes in K(+)
      riched (60 mmol.L-1) medium resulted in a marked activation of TM. PKC inhibitor
      polymyxin B (PMB) completely blocked the activation of K+ 60 mmol.L-1 on TM.
      Selective D2 receptor agonist quinpirole (QP), Ca2+ removal from incubation
      medium and CaM antagonist W7 failed to affect the activation. However, SPD
      enhanced the activation of K+ 60 mmol.L-1 on TM. Meanwhile, the incubation in K+
      60 mmol.L-1 also activated PKC. Neither QP nor SPD affected K+ depolarization
      induced activation of PKC. CONCLUSION: The activation of K+ depolarization on
      synaptosomal TM is enhanced by SPD and this activation is mediated by PKC rather
      than by PK II.

PMID- 10072894
TI  - Preproopiomelanocortin and preprodynorphin mRNA expressions in rat brain after
      electroacupuncture + droperidol.
AB  - AIM: To study the expression of preproopiomelanocortin (POMC) and preprodynorphin
      (PPD) mRNA following the combination of electroacupuncture (EA) with droperidol
      (Dro), a dopamine receptor antagonist. METHODS: The brains and spinal cords of
      Sprague-Dawley rats were sectioned after combination of EA with Dro, and the gene
      expression was investigated using nonradioactive in situ hybridization
      histochemistry (ISHH). RESULTS: Ten hours after EA, the POMC mRNA expression was
      enhanced; the expression was further enhanced when EA was combined with Dro. The
      expression of PPD mRNA showed regional difference in central nervous system
      (CNS): in spinal cord, EA enhanced the PPD mRNA expression and the combination of
      EA with Dro further promoted the expression; in the brain, the PPD mRNA
      expression after EA or combination of EA with Dro showed no obvious change in
      most regions (caudate-putamen, accumbens, arcuate nucleus of hypothalamus) or was
      decreased in supraoptic nucleus. CONCLUSION: Dro combined with EA promoted the
      expression of POMC mRNA in CNS and PPD mRNA in spinal cord, but reduced or had no
      effect on PPD mRNA expression in the brain.

PMID- 10072895
TI  - Action of 3 tyrphostin derivatives on casein kinase II from rat liver.
AB  - AIM: To study the action of tyrphostin on casein kinase (CK) II. METHODS: CK II
      was partially purified from rat livers by sequential DE52 and heparin-Sepharose
      chromatography. CK II activity was assayed by incubating CK II with
      dephosphorylated casein and [gamma-32P]ATP. RESULTS: AG34 inhibited the activity
      of CK II with IC50 33 (27-41) mumol.L-1. Both AG372 (121 mumol.L-1) and AG1112
      (150 mumol.L-1) displayed inhibitory effects on the activity of CK II. Kinetic
      studies of AG34 on CK II showed that it was noncompetitive with casein and ATP.
      CONCLUSION: AG34, AG372, and AG1112 were potent inhibitors of CK II, and the
      inhibitory action of AG34 was noncompetitive with casein and ATP.

PMID- 10072896
TI  - Oxidized low-density lipoproteins stimulate adhesion of monocytes to endothelial
      cells.
AB  - AIM: To study the effects of oxidized low-density lipoproteins (ox-LDL) on the
      adhesiveness of monocytes to endothelial cells. METHODS: LDL was obtained from
      healthy human plasma by ultracentrifugation, and oxidized by CuSO4 10 mumol.L-1.
      The assay of adhesion was performed using cultured bovine aortic endothelial
      cells (BAEC) and human peripheral blood monocytes. RESULTS: Pretreatment BAEC
      with ox-LDL enhanced monocyte adhesion to BAEC in time- and dose-dependent
      manner. ox-LDL as little as 10 mg.L-1 and 30 min of preincubation stimulated
      monocyte adhesion. Cycloheximide (Cyc, a protein synthesis inhibitor) 1 mg.L-1
      and staurosporine (Sta, a PKC inhibitor) 20 nmol.L-1 abolished the effect of ox
      LDL (60 mg.L-1), but dextran sulfate 20 mg.L-1 had no effect on monocyte
      adhesion. Phorbol 12-myristate 13-acetate (PMA) 1 nmol.L-1 and
      lysophosphatidylcholine (Lys) 6 mumol.L-1 mimicked the effects of ox-LDL and
      potentiated monocyte adhesion. Sta also suppressed the augmentative effects of
      Lys and PMA. CONCLUSION: ox-LDL enhances the adhesion of monocytes to BAEC
      through the activation of PKC.

PMID- 10072897
TI  - Inhibition of beta-myosin heavy chain gene expression in pressure overload rat
      heart by losartan and captopril.
AB  - AIM: To study the effects of losartan and captopril on beta-myosin heavy chain
      (MHC), and alpha-MHC gene expression. METHODS: Pressure overload was produced by
      abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were
      measured by Northern blot. RESULTS: In left ventricular myocardium of sham
      operated rats, the alpha-MHC mRNA predominated, while the beta-MHC mRNA was only
      detectable. In response AAC, there was a 70-fold increase in the beta-MHC mRNA (P
      < 0.01), while alpha-MHC mRNA reduced to 26% (P < 0.01). Losartan (3 mg.kg-1.d-1,
      i.g. for 11 d) to AAC rats caused inhibitions of beta-MHC by 96% and alpha-MHC by
      86% gene expression without lowering blood pressure. A reduction in beta-MHC mRNA
      was also seen in captopril-treated rats (30 mg.kg-1.d-1, i.g. for 11 d), but the
      inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan
      (44% vs 86%, P < 0.05). CONCLUSIONS: The shift of MHC isoform induced by pressure
      overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC
      gene expression. Inhibition of beta-MHC gene expression by losartan is achieved
      primarily by direct blockade of angiotensin II type I receptors in the
      myocardium, independent on hemodynamics.

PMID- 10072898
TI  - Effects of dexamethasone, ibuprofen, and ligustrazini on lipopolysaccharides
      induced tumor necrosis factor alpha production.
AB  - AIM: To study the influence of dexamethasone (Dex), ibuprofen (Ibu), and
      ligustrazini (Lig) on lipopolysaccharides (LPS)-induced tumor necrosis factor
      alpha (TNF alpha) gene expression (both mRNA and protein). METHODS: TNF alpha in
      supernatants of human whole blood was measured by ELISA; The TNF alpha mRNA was
      assessed by slot blot analysis. RESULTS: LPS-induced TNF alpha production was in
      a dose-dependent manner. TNF alpha levels in the whole blood increased markedly
      at 3 h and peaked at 6 h. The induction of TNF alpha mRNA was very rapid, peaking
      at 2 h after LPS challenge. Dex exerted inhibitory effects on TNF alpha
      production in a dose-dependent manner. Ibu and Lig had 2-phase effects on TNF
      alpha release. CONCLUSION: Dex, Ibu, and Lig affected TNF alpha gene expression,
      so they may be new approaches of anti-TNF alpha for treatment of sepsis.

PMID- 10072899
TI  - Heart hypertrophy induced by levothyroxine aggravates ischemic lesions and
      reperfusion arrhythmias in rats.
AB  - AIM: To develop a cardiac hypertrophic model in rats. METHODS: Rats were i.p.
      levothyroxine 0.5 mg.kg-1.d-1 x 10 d. The action potentials of right papillary
      muscles were recorded by standard glass-microelectrode technique. The left
      coronary artery was ligated followed by reperfusion and the apparent infarcted
      zone (AIZ) was determined by tetracycline fluoresence, and the superoxide
      dismutase (SOD) activity and malondialdehyde (MDA) product in myocardium were
      also measured. RESULTS: In the rats treated by levothyroxine, the heart was
      hypertrophic and the action potential duration (APD) and effective refractory
      period (ERP) were prolonged, the APD20, APD50, APD90, and ERP were prolonged by
      80%, 79%, 74%, and 68%, respectively. No changes in resting potential (RP),
      action potential amplitude (APA), and Vmax were produced. The incidence of heart
      arrest (8/8) and the risk of death (67 +/- 0) induced by ischemia-reperfusion in
      rats with hypertrophic heart was higher than those in normal rats (4/10 and 44 +/
      19, respectively). The AIZ was expanded markedly in hypertrophic heart, and
      attenuated by lidocaine and propranolol. CONCLUSION: Levothyroxine-induced heart
      hypertrophy is a suitable model for severe ischemia and arrhythmias in rats.

PMID- 10072900
TI  - Effect of mebendazole and praziquantel on glucosephosphate isomerase and
      glyceraldehydephosphate dehydrogenase in Echinococcus granulosus cyst wall
      harbored in mice.
AB  - AIM: To study effects of antihydatid drugs on glucosephosphate isomerase (GPI)
      and glyceraldehydephosphate dehydrogenase (GAPDH) in Echinococcus granulosus cyst
      wall. METHODS: Mice infected with the parasite for 8-10 months were treated i.g.
      with mebendazole (Meb) or praziquantel (Pra). The activities of GPI and GAPDH in
      the cysts were measured by the formation of NADH or NADPH. RESULTS: GPI activity
      in the cyst wall was 197 +/- 103 U, while that of GAPDH was 25 +/- 13 U. When
      infected mice were treated i.g. with Meb 25-50 mg.kg-1.d-1 for 7-14 d, no
      apparent effect on the GAPDH activity in the cyst was found. In mice treated i.g.
      with praziquantel (Pra) 500 mg.kg-1.d-1 for 14 d, the GAPDH activity in the cyst
      wall was inhibited by 26.5%. As to GPI activity only the group treated i.g. with
      Meb 25 mg.kg-1.d-1 for 14 d showed 33.2% inhibition of the enzyme in the
      collapsed cyst wall. CONCLUSION: GPI and GAPDH are not the major targets attacked
      by the antihydatid drug.

PMID- 10072901
TI  - Antioxidative and chelating activities of phenylpropanoid glycosides from
      Pedicularis striata.
AB  - AIM: To study the antioxidative and iron chelating activities of phenylpropanoid
      glycosides (PPG) isolated from a Chinese herb Pedicularis striata. METHODS:
      Antioxidative effects of PPG on lipid peroxidation induced by FeSO4-edetic acid
      in linoleic acid were measured by thiobarbituric acid method. Chelating
      activities of PPG for Fe2+ were tested by differential spectrum method. RESULTS:
      The reaction rates (A532.min-1) of lipid peroxidation were 0.0046 in the control,
      0.0021 in verbascoside group, and 0.0008 in isoverbascoside group. The chelating
      activity of isoverbascoside was 2-fold stronger than that of verbascoside.
      Permethyl verbascoside showed neither antioxidative nor chelating activities.
      CONCLUSION: The inhibitory effects of PPG with phenolic hydroxy groups on lipid
      peroxidation are owing to their chelating properties. Under physiological
      condition PPG-Fe2+ chelates are sufficiently stable. Thus PPG are able to inhibit
      the Fe(2+)-dependent lipid peroxidation in vivo through chelating Fe2+ and
      exhibit their therapeutic potential by the same mechanism in vitro.

PMID- 10072902
TI  - Effect of praeruptorin C on spontaneous [Ca2+]i transients in cultured myocardial
      cells of neonatal rats.
AB  - AIMS: To study the effects of praeruptorin C (Pra-C) on [Ca2+]i transients in
      cultured neonatal myocardiocytes. METHOD: Using Ca(2+)-sensitive fluorescent
      indicator, Fura 2-AM, spontaneous cytosolic Ca2+ transients were measured in
      cultured myocardial cells of neonatal rats. RESULTS: Pra-C 10, 30 mumol.L-1
      caused a decrease in the peak of Ca2+ transients. Pra-C 30 mumol.L-1 and 10-30
      mumol.L-1 inhibited partly the stimulatory effects of CaCl2 4.8 mmol.L-1 and Bay
      k 8644 100 nmol.L-1 on peak Ca2+ transients, respectively. Pra-C did not cause
      any marked change in the basal [Ca2+]i level between beats. Pra-C inhibited the
      reduced [Ca2+]i transients after inhibition of sarcoplasmic reticulum Ca2+
      release in ryanodine pretreated cells. CONCLUSIONS: Pra-C inferred with the Ca2+
      influx responsible for excitation-contraction coupling in myocardiocytes.

PMID- 10072903
TI  - Effects of Ro 31-8220 on lipopolysaccharides-induced hepatotoxicity and release
      of tumor necrosis factor from rat Kupffer cells.
AB  - AIM: To investigate protein kinase C (PKC) functions on lipopolysaccharide (LPS)
      induced hepatotoxicity, a new potent PKC inhibitor Ro 31-8220 (Ro) was used to
      detect its effect on LPS-induced hepatotoxicity in rat hepatocytes and tumor
      necrosis factor (TNF) release from rat Kupffer cells (KC). METHODS: Hepatocytes
      (containing KC) were incubated with LPS (10 mg.L-1) and Ro (0.1-10 mumol.L-1) for
      24 h, alanine aminotransferase (AlaA) leakage in the culture as indication of
      hepatotoxicity. The TNF activity in the supernatant of rat KC culture with LPS in
      the presence of Ro (0.1-10 mumol.L-1) was monitored by the L929 target cell lytic
      assay. RESULTS: Ro (0.1-10 mumol.L-1) reduced AlaA leakage in the hepatocyte
      culture. Ro inhibited dose-dependently the LPS-induced TNF production from rat
      KC. CONCLUSION: PKC inhibitor Ro protects the hepatocytes from LPS-induced
      cytotoxicity and inhibits the LPS-induced TNF production from rat KC.

PMID- 10072904
TI  - [Effects of melitten on isolated rat atrium].

PMID- 10072905
TI  - [Effects of harringtonine on peroxidation and dynamic microstructure of membrane
      lipids of myocardial sarcoplasmic reticulum in rat].

PMID- 10072906
TI  - Several new targets of antitumor agents.
AB  - Alpha-fetoprotein (AFP), as a hepatoma-promoting factor, has become a new target
      of anti-hepatoma agents. It is a new approach for the treatment of tumors to
      inhibit or block oncogene expression. Informational drugs are being developed for
      gene therapy applications as inhibitors of oncogene expression. The induction of
      tumor cell differentiation is another new strategy of drug therapy of tumors.
      Common action mode of many antitumor drugs is to induce apoptosis of tumor cells.
      Suicide genes, as targeting therapy of tumors, improve the present chemotherapy,
      exhibiting broad application prospects.

PMID- 10072907
TI  - Differential effects of pinacidil, cromakalim, and NS 1619 on electrically evoked
      contractions in rat vas deferens.
AB  - AIM: To compare the inhibitory action of electrically evoked contractions of rat
      epididymal vas deferens by pinacidil (Pin), cromakalim (Cro), and NS 1619.
      METHODS: Monophasic contractions were evoked by electric field stimulation in rat
      isolated epididymal half of vas deferens. RESULTS: Newly developed ATP-sensitive
      K+ channel openers, Pin and Cro, concentration-dependently reduced the
      electrically evoked (0.3 Hz, 1 ms pulse duration, 60 V) contractions and
      glibenclamide but not charybdotoxin antagonized the inhibitory effects of both
      agents. Pin shifted the concentration-response curve for norepinephrine to the
      right with reducing the magnitude of the maximum contraction in a glibenclamide
      sensitive fashion. The large-conductance Ca(2+)-activated K+ channel opener, NS
      1619, inhibited the electrically evoked contractions in a concentration-dependent
      manner. Charybdotoxin (100 nmol.L-1) partially reduced the effect of NS 1619 but
      glibenclamide (10 mumol.L-1) showed no effect. None of these 3 agents affected
      the basal tension. CONCLUSION: Both ATP-sensitive and Ca(2+)-activated K+
      channels presented in vas deferens smooth muscles involved in regulation of
      muscle contractility.

PMID- 10072908
TI  - Actions of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate in vascular
      smooth muscle cell cultures.
AB  - AIM: To study the effects of 8-(N,N-diethylamino)-n-octyl-3,4,5
      trimethoxybenzoate (TMB-8) on vascular smooth muscle (VSM) cells A7r5. METHODS:
      The effects of TMB-8 were investigated in A7r5 cell cultures with 45CaCl2.
      RESULTS: TMB-8 reduced the intracellular free Ca2+ concentration, [Ca2+]i in a
      Ca(2+)-free medium and blocked Ca2+ entry from the extracellular site in a
      regular Ca2+ medium. The equilibrated total cellular binding of Ca2+ was
      increased by TMB-8 whereas 45Ca2+ entry activated by both NE and KCl was
      inhibited. However, the NE-activated Ca2+ entry was not blocked by TMB-8 if TMB-8
      was added together with 45Ca2+ at a later time instead of by pretreatment.
      Similar to actions of NE and KCl, depletion of Ca2+ from sarcoplasmic reticulum
      (SR) would also activate Ca2+ entry, which was blocked by TMB-8. When TMB-8 was
      rinsed out alone or together with NE after pretreatment with NE plus TMB-8 in VSM
      cells, the inhibitory effect of TMB-8 was not affected. CONCLUSION: TMB-8 not
      only blocks Ca2+ entry from the extracellular site, but also enhances Ca2+ uptake
      into SR which, indirectly inhibits Ca2+ entry from the extracellular site.

PMID- 10072909
TI  - Effects of isolation housing and timing of drug administration on amikacin
      kinetics in mice.
AB  - AIM: To study the influences of social condition and drug administration time on
      amikacin metabolism in mice. METHODS: Forty Male ICR mice were randomly assigned
      into 4 groups according to 1) housing condition: individual housing (I, one mouse
      in a cage) or aggregated housing (A, 10 mice in a cage) and 2) drug
      administration time: at midday (D) or at midnight (N), i.e. I-D, I-N, A-D, and A
      N groups. Amikacin was injected s.c. 15 mg.kg-1 after 4 wk of raising at D or N.
      Blood samples were taken at 5, 10, 15, 20, 30, and 60 min after medication in
      each mouse. Plasma amikacin was measured by enzyme immunoassay. The concentration
      time data were fitted with one-compartment open model in each mouse and data were
      analyzed with group t test. RESULTS: The clearance (Cl) of amikacin was larger
      and the half-life (T1/2) was shorter in A-N group than in A-D or I-N groups
      respectively. AUC(0-1) in A-N group was less than in I-N group. No differences of
      kinetic parameters between 2 isolated housing (I-D and I-N) groups were found.
      CONCLUSION: Aggregated housing and midnight drug administration increased the
      disposition of amikacin.

PMID- 10072910
TI  - Anti-inflammatory and ulcerogenic effects of 3-(N,N-diethylamino)
      propylindometacin HCl.
AB  - AIM: To study anti-inflammatory effects of a novel indometacin ester, 3-(N,N
      diethylamino) propyl-indometacin HCl (prodrug) and its ulcerogenicity in fats.
      METHODS: Carrageenin (Car)-induced paw edema and ulcer index were examined.
      RESULTS: Car-induced paw edema was inhibited by 36.6% (P < 0.01) at 3 h and 34.6%
      (P < 0.01) at 5 h after a single i.p. injection of the prodrug 7.09 mg.kg-1. On
      the same molar basis, indometacin (Ind) 5 mg.kg-1 i.p. inhibited edema by 45.6%
      at 3 h and 39.2% at 5 h, however, there was no statistical significant difference
      (P > 0.05) between the edema-inhibitory effect of the prodrug and that of Ind.
      The dose 10 micrograms/paw exhibited 64% inhibition of the swelling, the prodrug
      > 10 micrograms/paw showed no additional inhibition of swelling; the acute
      gastric lesion properties of the prodrug were much lower than those of Ind 6 h
      after p.o. CONCLUSION: The prodrug is a potent anti-inflammatory agent with lower
      ulcerogenicity in the stomach.

PMID- 10072911
TI  - Sorbitol accumulation in rats kept on diabetic condition for short and prolonged
      periods.
AB  - AIM: To study the influence of the course of diabetes, aging, and glycemia on the
      sorbitol accumulation in diabetic rats. METHODS: Streptozocin (Str) diabetic rats
      were obtained by Str i.v. (35 mg.kg-1). Glycemia and sorbitol levels from sciatic
      nerve and lens were measured after 1 d, 2, 5, and 8 months of diabetes. Sorbitol
      concentrations in serum, heart, diaphragm, small intestine, and kidney after 8
      months of diabetes were measured. RESULTS: Diabetic rats after Str injection
      showed hyperglycemia (> 1.7 g.L-1), hyperphagia, polyuria, polydipsia, and loss
      of body weight. Sorbitol levels in lens and sciatic nerve increased in normal and
      diabetic rats; the increase was higher in diabetic rats. No relationship was
      shown between glycemia and sorbitol levels. An increased sorbitol level after 8
      months of diabetes was found in small intestine and kidney. CONCLUSION: The
      sorbitol levels increased in lens and sciatic nerve with aging and this process
      was accelerated by diabetes.

PMID- 10072912
TI  - Attenuation of myocardial injury due to oxygen free radicals (OFR) by
      pretreatment with OFR or calcitonin gene-related peptide.
AB  - AIM: To study the cardioprotective effects of oxygen free radicals (OFR) and
      calcitonin gene-related peptide (OGRP) pretreatment on myocardial damages due to
      OFR in isolated perfused rat heart. METHODS: The hearts were perfused in a
      Langendorff mode. OFR were generated by electrolysis of Krebs-Henseleit (K-H)
      solution. RESULTS: OFR pretreatment reduced the impairment of cardiac contractile
      function, the decrease of coronary flow and the increase of creatinine kinase
      (CK) release due to OFR, and the effect exhibited period dependence and cycle
      dependence. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an inhibitor of
      protein kinase C, abolished the protection of OFR pretreatment (CK release = 110
      +/- 7, 215 +/- 23, 169 +/- 14, 240 +/- 30, and 113 +/- 19 kU.L-1 for control,
      OFR, OFR pretreatment, OFR pretreatment plus H-7, and H-7, respectively). CGRP
      pretreatment also protected the myocardium damages elicited by OFR in isolated
      perfused rat heart. CONCLUSIONS: OFR or CGRP pretreatment protected myocardium
      against injury elicited by OFR, and the effect of OFR pretreatment was related to
      the activation of PKC.

PMID- 10072913
TI  - Molecular modeling of mu opioid receptor and receptor-ligand interaction.
AB  - AIM: To construct the 3D structural model of mu opioid receptor (mu OR) and study
      the interaction between mu OR and fentanyl derivatives. METHODS: The 3D structure
      of mu OR was modeled using the bacteriorhodopsin (bRh) as a template, in which
      the alignments of transmembrane (TM) of bRh and mu OR were achieved by scoring
      the alignment between the amino acid sequence of mu OR and the structure of bRh.
      The fentanyl derivatives were docked into the 7 helices of mu OR and the binding
      energies were calculated. RESULTS: (1) The receptor-ligand interaction models
      were obtained for fentanyl derivatives. (2) In these models, the fundamental
      binding sites were possibly Asp147 and His297. The negatively charged oxygen of
      Asp147 and the positively charged ammonium group of ligand formed the potent
      electrostatic and hydrogen-binding interactions. Whereas the interactions between
      the positively charged nitrogen of His297 and the carbonyl oxygen of ligand were
      weak. In addition, there were some pi-pi interactions between the receptor and
      the ligand. (3) The binding energies of the receptor-ligand complexes had a good
      correlation with the analgesic activities (-lg ED50) of the fentanyl derivatives.
      CONCLUSION: This model is helpful for understanding the receptor-ligand
      interaction and for designing novel mu OR selective ligands.

PMID- 10072914
TI  - Molecular modeling of voltage-gated potassium channel pore.
AB  - AIM: To build a structure model for the pore of voltage-gated Shaker potassium
      channel and examine its validity. METHODS: (1) Structural restraints were derived
      from experimental and theoretical studies; (2) An initial structural motif
      satisfying the derived restraints was first constructed, and further refined by
      restrained molecular mechanics; (3) The quality of the model was judged by the
      criterion that whether it could clarify molecular mechanisms of channel functions
      and explain the known experimental facts. RESULTS: (1) A computer pore structure
      was proposed, in which the residues within signature sequence (corresponding to
      Shaker 439-446) dipped into the membrane and formed the narrow part of the pore
      in a non-periodic conformation, while the other residues in the P region
      constituted the outer mouth of the pore; (2) The ion selectivity was achieved
      through cation-pi orbital interaction mechanism at position 445 and oxygen cage
      mechanism at position 447; (3) Different binding modes led to different affinity
      of CTX and AgTx2 to channel; and (4) The inside of pore was dominated by negative
      electrostatic potential. CONCLUSION: The model proposed was consistent with the
      derived restraints from the experimental results.

PMID- 10072915
TI  - Kinetic properties of nicotinic receptors in cultured rat sympathetic neurons
      from superior cervical ganglia.
AB  - AIM: To analyze the kinetic properties of the effect of nicotine on nicotinic
      acetylcholine receptors (nAChR) in the cultured sympathetic neurons from neonatal
      rat superior cervical ganglia (SCG). METHODS: The whole-cell recording method of
      patch-clamp technique was used to record the currents induced by different
      concentrations of nicotine. The concentration-response of nicotine was fitted
      with Clark equation. RESULTS: Hill coefficient (1.097) was determined by fitting
      the nicotine responses of neuronal nAChR with Clark equation. The theoretical
      values of nicotine effect, calculated with Clark equation with H = 1, were
      basically identical with the practically recorded currents. CONCLUSIONS:
      Interaction of nicotine and nAChR in rat SCG fits a single binding site model.

PMID- 10072916
TI  - Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro.
AB  - AIM: To study the direct effect of enalapril on cellular electrophysiology of
      myocardium. METHODS: Conventional microelectrodes technique was used to record
      the action potentials (AP) of guinea pig papillary muscles. RESULTS: Enalapril
      caused an increase of the AP amplitude (APA) and the resting potential (RP) in a
      concentration-dependent manner without any significant change of AP duration,
      Vmax and overshoot of AP. Superfusion of ouabain 0.5 mumol.L-1 reduced APA and
      RP, induced stable delayed after-depolarizations (DAD) at different basic cycle
      lengths (BCL) in a frequency-dependent manner. At BCL 200 ms, the amplitude of
      DAD was large enough to induce nonsustained triggered activity (TA). In
      additional presence of enalapril 10 mumol.L-1, the DAD amplitude at 500, 400,
      300, and 200 ms were decreased from 5.3 +/- 2.3, 5.9 +/- 2.8, 7.4 +/- 2.1, and
      8.9 +/- 1.3 to 2.6 +/- 0.7, 3.1 +/- 1.0, 3.7 +/- 1.5, and 5.3 +/- 1.1 (mV)
      respectively, all P < 0.01. The compensation intervals were increased in a
      similar frequency-dependent manner. The number of TA induced at BCL 200 ms was
      decreased from 3.6 +/- 0.7 to 0.8 +/- 0.2 (P < 0.05). CONCLUSION: Enalapril
      directly inhibits DAD and TA induced by ouabain through increasing RP and APA,
      which may contribute to its anti-arrhythmic effect.

PMID- 10072917
TI  - Binding properties of C-truncated delta opioid receptors.
AB  - AIM: To study the role of C-terminal delta opioid receptor involved in ligand
      binding affinity and selectivity. METHODS: The 31 amino acid residues of C
      terminal truncated delta opioid receptors and the wild-type were expressed stably
      in Chinese hamster ovary (CHO) cells, respectively. Then the ligand binding
      properties of the products were studied by receptor binding assay. RESULTS: A
      typical mutated receptor clone CHO-T and a wild-type receptor clone CHO-W were
      obtained. The Kd values of [3H] diprenorphine (Dip) and [3H]leucine-2-alanine
      enkephalin (DADLE) bound to CHO-T were similar to CHO-W. Both the specific
      [3H]Dip bindings of CHO-T and CHO-W were strongly inhibited by delta selective
      agonists with similar Ki, but neither by mu nor kappa selective agonists.
      CONCLUSION: The C-terminal of the delta opioid receptor is not involved in the
      ligands binding affinity and selectivity.

PMID- 10072918
TI  - Modulation of phosphatidylinositol turnover on central nicotinic receptors.
AB  - AIM: To study the modulatory effects of phosphatidylinositol (PI) turnover on
      nicotinic receptors in CNS, and to study the relationship between brain nicotinic
      receptors and PI turnover. METHODS: Effects of inositol phosphatase inhibitor
      lithium chloride (LiCl) and muscarinic receptor agonist oxotremorine (Oxo) on
      nicotine-induced convulsions were investigated in mice. RESULTS: The effects of
      nicotine for producing convulsions were modified by LiCl 2.5-10 mmol.kg-1,
      revealing the convulsive effects of nicotine > 0.8 mg.kg-1 were increased by
      acute pretreatment with LiCl rather than oxotremorine. Mice were given LiCl 5.0
      mmol.kg-1 once a day for 7 d, the ED50 value of nicotine for producing
      convulsions was increased from 0.58 to 0.97 mg.kg-1, suggesting that the
      sensitivity of central nicotinic receptors for mediating convulsions was
      decreased by chronic treatment with LiCl. CONCLUSION: The functions of central
      nicotinic receptors were modulated by PI turnover.

PMID- 10072919
TI  - Antagonistic effects of extract from leaves of ginkgo biloba on glutamate
      neurotoxicity.
AB  - AIM: To determine whether the extract of leaves of Ginkgo biloba L (EGb) and
      several active constituents of EGb have protective effects against glutamate
      (Glu)-induced neuronal damage. METHODS: Microscopy and image analysis of nucleus
      areas in the arcuate nuclei (AN) of mice were made. The neuronal viability in
      primary cultures from mouse cerebral cortex was assessed using MTT [3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] staining and the
      intracellular free calcium concentration ([Ca2+]i) of single neuron was measured
      using Fura-2. RESULTS: EGb (2.5 mg.L-1) and its constituent ginkgolide B (Gin B,
      2 mg.L-1) protected the neuronal viability against Glu-induced injury, and
      prevented the Glu-induced elevation in [Ca2+]i. EGb (3-10 mg.kg-1) attenuated the
      decrease of nucleus areas in arcuate nuclei induced by Glu (1 g.kg-1, s.c.).
      CONCLUSION: EGb and Gin B prevent neurons from Glu neurotoxicity through
      reduction of the rise in [Ca2+]i.

PMID- 10072920
TI  - Effects of dauricine, quinidine, and sotalol on action potential duration of
      papillary muscles in vitro.
AB  - AIM: To compare the characteristics of dauricine, sotalol, and quinidine on
      action potential duration (APD). METHODS: Using intracellular microelectrode
      method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20
      mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD
      prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5
      +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in
      lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD
      exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10
      mumol.L-1 were less effective in lengthening APD at short cycle lengths. The
      effect of quinidine and sotalol on APD exhibited reverse use-dependence.
      CONCLUSION: [corrected] The effect of dauricine on APD depends on activation
      frequency.

PMID- 10072921
TI  - Imipramine blocks the transient outward potassium current in rat ventricular
      myocytes.
AB  - AIM: To examine the effects of imipramine on transient outward potassium current
      (I(to) in rat ventricular myocytes. METHODS: The patch-clamp whole-cell recording
      techniques were used. RESULTS: Imipramine resulted in a concentration-dependent
      inhibition of I(to) with the IC50 of 6.0 mumol.L-1 and a concentration-dependent
      acceleration of I(to) inactivation. The blocking showed no difference at
      different testing membrane potentials. Imipramine produced slight effects (about
      3 and 4 mV, respectively) on steady-state activation and inactivation curves of
      I(to), and tended to prolong the recovery of I(to) from inactivation (tau control
      = 37 +/- 11 ms; tau drug = 58 +/- 17 ms), but not significant (n = 4, P > 0.05).
      The inhibitory effect of imipramine on Ito was increased when the prepulses were
      prolonged progressively from 0 to 120 ms. (tau control = 22 +/- 8 ms; tau drug =
      14 +/- 5 ms). CONCLUSIONS: Imipramine blocked Ito in concentration-dependent but
      voltage-independent manners, and with "open channel blocking" properties.

PMID- 10072922
TI  - Effect of 3,6-dimethamidodibenzopyriodonium citrate on Ca2+ in rabbit platelet in
      vitro.
AB  - AIM: To study the effect of 3,6-dimethamidodibenzopyriodonium citrate (I-65) on
      the cytoplasmic free Ca2+ ([Ca2+]i) concentration in rabbit platelet. METHODS:
      Measurement of the cytosolic Ca2+ of platelets in vitro by using Quin 2-AM
      fluorescence technique. RESULTS: In the presence of CaCl2 1 mmol.L-1, I-65 (10,
      20, and 30 mumol.L-1) reduced the rise in [Ca2+]i induced by thrombin and
      calcimycin from 142 +/- 22 nmol.L-1 and 124 +/- 18 nmol.L-1 to 118 +/- 20, 78 +/-
      12, 40 +/- 10 nmol.L-1, respectively and 108 +/- 15, 77 +/- 14, 37 +/- 14 nmol.L
      1, respectively. In the presence of egtazic acid 2 mmol.L-1, I-65 (10, 20, and 30
      mumol.L-1), reduced the Ca2+ release induced by thrombin from 52 +/- 11 nmol.L-1
      to 34 +/- 9, 19 +/- 6, and 11 +/- 5 nmol.L-1, respectively. In addition, I-65
      (10, 20, and 30 mumol.L-1) also reduced the Ca2+ influx induced by thrombin from
      91 +/- 13 nmol.L-1 to 84 +/- 15, 58 +/- 15, and 28 +/- 19 nmol.L-1, respectively.
      CONCLUSION: I-65 inhibited not only the Ca2+ release, but also the influx of Ca2+
      in activation platelet.

PMID- 10072923
TI  - Inhibitory effects of copper-aspirin complex on platelet aggregation.
AB  - AIM: To study the inhibitory effects of copper-aspirin complex (CuAsp) on
      platelet aggregation. METHODS: With adenosine diphosphate the effects of CuAsp on
      platelet aggregation in vitro or in vivo were investigated. Radioimmunoassay and
      fluorophotometry were used to measure thromboxane B2 (TXB2) generation from
      platelets, the levels of TXB2 and of 6-keto-PGF1 alpha in plasma and the platelet
      serotonin release reaction. RESULTS: In vitro, CuAsp inhibited arachidonic acid
      (AA)-induced aggregation (IC50 = 17 mumol.L-1, 95% confidence limits: 9-33
      mumol.L-1), the release of 5-HT (IC50 = 19 mumol.L-1, 95% confidence limits: 10
      30 mumol.L-1), and TXB2 generation from platelets (P < 0.05). CuAsp 10 mg.kg-1
      i.g. selectively inhibited AA-induced aggregation, and increased the 6-keto-PGF1
      alpha concentration in plasma while decreased that of TXB2. CONCLUSION: CuAsp, in
      vitro or in vivo, shows more potent inhibitory effects on AA-induced aggregation
      than aspirin (Asp), related to the inhibition of platelet cyclooxygenase and the
      release of active substances from platelets.

PMID- 10072924
TI  - Effect of artemether on glucose uptake and glycogen content in Schistosoma
      japonicum.
AB  - AIM: To study the effect of artemether (Art) on glucose uptake and glycogen
      content in schistosomes. METHODS: Schistosomes recovered from mice treated
      intragastrically with Art 300 mg.kg-1 for 24-48 h, were incubated in the drug
      free medium containing [U-14C]glucose 11.1 MBq.L-1. The glycogen content, [U
      14C]glucose uptake, and incorporation of [U-14C]glucose into worm glycogen in
      both male and female worms were determined. RESULTS: When above-mentioned
      schistosomes were exposed to drug-free medium containing [U-14C]glucose for 1-24
      h, the glycogen contents of male and female worms decreased 27%-61% and 39%-78%,
      respectively. Only 3 out of 6 male worm groups showed 23%-35% decrease in glucose
      uptake, while much less glucose uptake was found in female worms in all groups
      with reduction rates of 18%-38%. Apart from 2 male groups no apparent change in
      the incorporation of [U-14C]glucose into the worm glycogen was seen. CONCLUSIONS:
      Art-induced glycogen reduction in schistosomes was related to an inhibition of
      glycolysis rather than an interference with glucose uptake.

PMID- 10072925
TI  - Effect of DL111-IT on progesterone biosynthesis and viability of rat luteal cells
      in vitro.
AB  - AIM: To study the influence of DL111-IT on progesterone biosynthesis of cultured
      luteal cells (LC). METHODS: LC viability was assessed with trypan blue dye
      exclusion and progesterone concentration was measured with radioimmunoassay.
      RESULTS: DL111-IT decreased the viability of LC after 24-h incubation, its ED50
      being 7.7 (95% confidence limits: 7.1-8.5) mg.L-1. DL111-IT inhibited basal
      secretion of progesterone in a concentration-dependent manner, and 3 mg.L-1
      decreased progesterone concentration by 25% vs control. DL111-IT 3 mg.L-1 also
      inhibited the stimulatory effect of forskolin (cAMP activator) 10 mumol.L-1 and
      pregnenolone [converted to progesterone by 3 beta-hydroxysteroid dehydrogenase
      isomerase complex (3 beta-HSD)] 10 mumol.L-1 on progesterone production in
      cultured LC, and their inhibitory rates were 43% and 155%, respectively. At the
      same concentration, DL111-IT did not influence hCG-induced progesterone
      production. CONCLUSION: DL111-IT inhibited progesterone synthesis by suppressing
      the conversion of pregnenolone to progesterone (inactivating 3 beta-HSD) and
      suppressed the activity of cAMP. DL111-IT 6-24 mg.L-1 decreased the viability of
      LC.

PMID- 10072926
TI  - Effect of tetrandrine on proto-oncogene c-fos expression in rat cerebrum.
AB  - AIM: To detect the effect of tetrandrine (Tet) on c-fos gene expression in
      cerebrum induced by lindane, a neurotoxicant which activates Ca2+ channels.
      METHODS: Northern and dot blotting, dual wavelength thin layer chromatography
      scanner, were used in this study. RESULTS: Lindane 30 mg.kg-1 given by
      intragastric gavage (i.g.) increased the expression of c-fos gene to 146 mm2 in
      rat cerebrum 1 h after treatment. Tet 1, 2, and 4 mg.kg-1 given by i.g. 30 min
      prior to lindane reduced c-fos gene expression in a concentration-dependent
      manner. Expressed genes reached only 86, 40, and 39 mm2, respectively.
      CONCLUSION: Tet inhibited c-fos gene expression in rat cerebrum induced by Ca2+
      agonist-lindane.

PMID- 10072927
TI  - Effect of quercetin on activities of protein kinase C and tyrosine protein kinase
      from HL-60 cells.
AB  - AIM: To study the effect of quercetin (Que) on the activities of cytosol and
      membrane protein kinase C (PKC) and tyrosine protein kinase (TPK) from HL-60
      cells in vitro. METHODS: The number of viable cells was counted by a trypan blue
      dye exclusion test. PKC activity was assayed by incubating PKC with histone III S
      and [gamma-32P]ATP. TPK activity was assayed by incubating TPK with poly
      glutamate.tyrosine (4:1). RESULTS: Que inhibited the proliferation of HL-60 cells
      in a concentration-dependent manner, its IC50 was 29 (22-37) mumol.L-1 after 48-h
      treatment; Que strongly inhibited the activity of cytosol PKC and membrane TPK
      with IC50 31 (20-48) mumol.L-1, 24 (13-45) mumol.L-1, respectively, but did not
      affect membrane PKC and cytosol TPK from HL-60 cells in vitro. CONCLUSION: The
      inhibitory effect of Que on the growth of tumor cells is related to its
      inhibitory effects on PKC and/or TPK.

PMID- 10072928
TI  - Ketamine-induced peripheral analgesia in rats.
AB  - AIM: To examine whether ketamine may directly act at peripheral nociceptors to
      produce analgesia. METHODS: Wistar rats were anesthetized with urethane. As a
      nociceptive flexion reflex (FR), C responses from the posterior biceps
      semitendinosus (PBST) muscle was evoked by electrical stimulation (2 ms, 80 V, 2
      3 pulses, 0.5 Hz) via a pair of stainless steel needles inserted subcutaneously
      applied to the two toes of ipsilateral hindpw. RESULTS: Subcutaneous injection of
      ketamine (36 mmol.L-1, 5 microL) into the ipsilateral hindpaw produced an
      inhibition of C responses. At 9 min after application of ketamine, injection of
      naloxone (1%, 5 microL) into the same area annulled ketamine-induced inhibition.
      CONCLUSION: Ketamine as a dissociate anesthetic acts on peripheral nociceptors to
      produce analgesia, which is related to activity of peripheral opioid receptors.

PMID- 10072929
TI  - [Increase of mitogen-activated protein kinase activity in rat brain after
      injection of argipressin (4-8)].
AB  - AIM: To study the changes of mitogen-activated protein kinase (MAPK) activity in
      rat brain stimulated by argipressin (4-8) (AVP (4-8)) (s.c.). METHODS: Wistar rat
      was treated with AVP (4-8). MAPK activity in rat brain was assayed by
      phosphorylation of its specific substrate myelin basic protein (MBP) after the
      cytosolic extracts fractionated by MONO-Q anion-exchange chromatography. RESULTS:
      The activity of 44 kDa MAPK in rat brain was significantly enhanced by AVP (4-8).
      The enhancement of MAPK activity in hippocampus was suppressed 80% by ZDC(C)CPR,
      an antagonist of AVP(4-8). The level of 44 kDa MAPK protein had no detectable
      differences between the administration groups and control. In rat hippocampal
      slices, similar results were obtained. CONCLUSION: The increasement of 44 kDa
      MAPK activity stimulated by AVP(4-8) was mediated by its specific receptor, and
      was a short-period process activated by protein phosphorylation, but not by
      protein expression. MAPK was involved in the signal transduction pathway induced
      by AVP(4-8).

PMID- 10072930
TI  - Modulation by nicotine on muscarinic receptor-effector systems.

PMID- 10072931
TI  - Inhibitory effect of artemether on proteinase of Schistosoma japonicum.
AB  - AIM: To study the effect of artemether (Art) on the thio proteinase
      ("hemoglobinase", Hem) of Schistosoma japonicum. METHODS: Hem was extracted from
      S japonicum adults. The inhibitory effect of Art on the activity of Hem to
      degrade human hemoglobin (Hgb) was examined with UV-photometer at 280 nm, SDS
      PAGE and scanning at 600 nm on a chromoscanner. RESULTS: Human Hgb was degraded
      at pH 4.0 by the Hem. The activities of Hem preincubated at 37 degrees C with Art
      0.14, 1.4, and 14 mmol.L-1, were inhibited by 30.2%, 39.8%, and 45.0%,
      respectively. CONCLUSION: Art possesses an inhibitory effect to Hem of S
      japonicum.

PMID- 10072932
TI  - Protection of ebselen against anoxic damage of cultured neurons of cerebral
      cortex.
AB  - AIM: To study the protective effect of ebselen on anoxic damage of brain cells.
      METHODS: On d 10 after plating of the cortical neurons from 1-d-old rat, cultures
      were placed under 95% N2 + 5% CO2 for 2-6 h. Lactate dehydrogenase (LDH) in
      supernatant, thiobarbituric acid reactive substance (TBARS) and glutathione
      peroxidase (GSH-Px) activity of neurons were determined. RESULTS: Under anoxia,
      efflux of LDH and TBARS from cultured neurons increased while GSH-Px activity
      decreased. Ebselen reduced the efflux of LDH and TBARS in a dose-related manner
      and increased the total GSH-Px activity. CONCLUSION: Ebselen can protect neurons
      from anoxic damage.

PMID- 10072933
TI  - Production of anti-peptide antibody of rat brain nitric-oxide synthase.
AB  - AIM: To raise antibody of rat brain nitric-oxide synthase (bNOS) through
      immunizing animal with a peptide of bNOS that can represent the holoprotein.
      METHODS: The amino acid sequence for the bNOS was analyzed by GenePro computer
      program. According to the hydrophilicity, hydrophobicity, antigenicity, and the
      potentiality to form protein second structures of alpha-helix, beta-sheet and
      beta-turn, the structure of bNOS was predicted. The peptide 277-287 was selected
      that was predicted to be in the antigen epitope of bNOS. The peptide was
      chemically synthesized, coupled to keyhole limphet hemocyanin carrier protein and
      injected into rabbits to raise antibody. The specificity of the antibody was
      tested by enzyme-linked immunosorbent assay, immunohistochemistry, and Western
      blotting. RESULTS: The antibody bound the protein in rat cerebellum extract. In
      Western blotting, the antibody bound the protein band of 150 kDa in SDS-PAGE, and
      the binding was inhibited by peptide conjugated with carrier protein. In
      immunohistochemistry, the stain was collocated with the stain in NADPH
      dehydrogenase histochemistry. CONCLUSION: The antibody against the peptide
      recognized the natural bNOS in rat brain, and the peptide 277-287 was located on
      the surface of bNOS.

PMID- 10072934
TI  - Chimeric dopamine D2/angiotensin AT1 receptors: role of the length of third
      intracellular loop of D2 receptors in conferring specificity of receptor binding
      and G-protein coupling.
AB  - AIM: To define roles of the third intracellular loop (IL3) length of G-protein
      coupled receptors in conferring the specificity for receptor binding and G
      protein coupling. METHODS: By polymerase chain reaction (PCR), the IL3 of D2
      receptor was replaced with the counter part of AT1 receptor which has the
      shortest loop among all G-protein coupled receptors. D2/AT1 receptor cDNA was
      then stably transfected into Chinese hamster ovary cells and a clone with high
      level expression was obtained for receptor binding and agonist-induced
      phosphatidylinositols (PI) turnover experiments. RESULTS: Comparing to the D2
      receptor, D2/AT1 chimeric receptor had lower affinities for all D2 receptor
      antagonists tested (spiperone, haloperidol, (+)-butaclamol, chlopromazine,
      clozapine, trifluoperdazine) and different affinity profiles to agonists
      (apomorphine, dopamine, quinpirole, bromocriptine). But the chimeric receptor
      failed to couple to G-protein and subsequent stimulation of PI turnover.
      CONCLUSION: The length of IL3 of D2 receptor participates defining recpetor
      binding sites conformation, and structure beyond IL3 may affect receptor G
      protein coupling.

PMID- 10072935
TI  - Effect of saponins of Panax notoginseng on synaptosomal 45Ca uptake.
AB  - AIM: To explore the calcium uptake antagonism of saponins of Panax notoginseng
      (PNS). METHODS: Synaptosomes were prepared from rat cerebral cortex by using
      differential Ficoll gradients. The effects of PNS on synaptosomal 45Ca uptake
      were measured in vitro or after acute treatment. RESULTS: PNS 50-800 mg.L-1
      produced a concentration-rated inhibition of Ca2+ uptake [IC50 = 111 (46-176)
      mg.L-1]. Both initial and maximal uptake were inhibited. Similar effect was
      obtained after acute PNS treatment with 200 mg.kg-1 i.p. The blocking effect of
      PNS was reversed by calcium in media. CONCLUSION: PNS is a calcium channel
      blocker in neurons.

PMID- 10072936
TI  - No correlation between side-chain of propranolol oxidation and S-mephenytoin 4'
      hydroxylase activity.
AB  - AIM: To determine if any correlation between the side-chain oxidative capacity
      for propranolol and S-mephenytoin 4'-hydroxylase (cytochrome P-450 2C19, CYP2C19)
      activity in healthy Chinese of Han nationality. METHODS: S-mephenytoin oxidative
      metabolite 4'-hydroxymephenytoin (4'OH-M), S- and R-mephenytoin, and naphthoxyl
      actic acid (NLA) excreted in urine, and propranolol in plasma were measured after
      14 healthy extensive metabolizers of S-mephenytoin oxidation were given a single
      oral dose of racemic mephenytoin 100 mg and racemic propranolol 80 mg,
      respectively. S/R-mephenytoin in urine was determined by chiral capillary gas
      chromatography with nitrogen-phosphorus detection, 4'-OH-M in urine by reversed
      phase liquid chromatography (RPLC) with ultraviolet detection, and plasma
      propranolol or urinary NLA by the RPLC with fluorescence detection. RESULTS: No
      significant correlations were found between the partial metabolic clearance (Clm)
      of propranolol to NLA and 8 h urinary S/R ratio of mephenytoin (rs = -0.0484; P =
      0.8695), nor between the Clm and log10 of 8 h urinary excretion of 4'-OH-M (rs = 
      0.1077; P = 0.7140). CONCLUSIONS: CYP2C19 is not a principal P-450 isozyme
      responsible for the in vivo side-chain oxidation of propranolol in the Chinese.

PMID- 10072937
TI  - Molecular modeling of interaction between delta opioid receptor and 3
      methylfentanylisothiocyanate.
AB  - AIM: To construct a 3D structural model of delta opioid receptor (delta OR) and
      study its interaction with 3-methylfentanylisothiocyanate (SuperFIT). METHODS:
      Using the bacteriohodopsin as a template, the 3D structure of delta OR was
      modeled; SuperFIT was docked into its inside. RESULTS: The interaction model
      between delta OR and (3R, 4S)-SuperFIT was achieved, in which the important
      binding sites possibly were Asp128, Ser106, Phe104, Tyr308, and Pro315. Asp128
      formed the electrostatic and hydrogen-binding interactions with the protonated
      nitrogen on piperidine of the ligand. Ser106 formed the electrostatic interaction
      with the N atom of isothiocyano group of the ligand; whereas Phe104, Tyr308, and
      Pro315 formed the hydrophobic interactions with the S atom of isothiocyano group.
      In addition, there were some other interactions between delta OR and the ligand.
      CONCLUSION: The residues Phe104, Tyr308, Pro315, and Ser106 of delta OR are
      crucial to the delta selectivity of the ligand, which is beneficial for designing
      novel delta-selective ligand.

PMID- 10072938
TI  - Characteristics of tetrahydroprotoberberines on dopamine D1 and D2 receptors in
      calf striatum.
AB  - AIM: To study the characteristics of tetrahydroprotoberberines (THPB) on dopamine
      D1 and D2 receptors and elucidate their structure-activity relationship. METHODS:
      Radioligand assay in vitro with a two-site model program analysis. RESULTS: Four
      THPB with two hydorxyl groups on C2 and C9 or C2 and C10 exhibited RH and RL two
      binding sites to D1 receptors and guanosine triphosphate regulated the RH binding
      site of SPD and THPB-132A in competition assay, while eleven THPB including
      nonhydroxy-THPB, monohydroxy-THPB, and THPB with two hydroxyl groups attaching to
      C3 and C10 showed one binding site to D1 receptors under the same conditions.
      However, the tested eleven THPB all manifested one binding site to D2 receptors
      in competition assay, and the 2-hydroxy-THPB had the most potent affinity for D2
      receptors. CONCLUSION: Dihydroxy-THPB with two hydroxyl groups attaching to C2
      and C9 or C2 and C10 possess the intrinsic activity of agonist to D1 receptors,
      while the other THPB do not. The tested eleven THPB all are the antagonists of D2
      receptors.

PMID- 10072939
TI  - Carbamazepine facilitates effects of GABA on rat hippocampus slices.
AB  - AIM: To study the influence of carbamazepine (Car) on GABA effect in hippocampus.
      METHODS: Evoked potentials were recorded on pyramidal cells in CA1 after
      stimulation (0.5 Hz, 50 microseconds) to Schaffer collaterals in rat hippocampal
      slices (350 microns). RESULTS: Car 0.1 and 0.2 mmol.L-1 did not affect field
      potentials, whereas Car 0.2 mmol.L-1 plus GABA (0.1-1 mmol.L-1) gave rise to a
      stronger inhibition on field potentials than that of GABA alone. Bicuculline did
      not reverse Car facilitation on GABA inhibition on field potentials. (-)-Baclofen
      was more effective in inhibiting field potentials than GABA. Car 0.2 mmol.L-1
      plus (-)-baclofen (1-5 mumol.L-1) brought an inhibition stronger than that of (-)
      baclofen alone. CONCLUSION: Car facilitates the effects of GABA on pyramidal
      cells in hippocampal CA1 region, probably related to GABAB receptors.

PMID- 10072940
TI  - Effects of MCI-154 on calcium sensitivity of contractile system and calcium
      release from sarcoplasmic reticulum in saponin-skinned rat myocardium.
AB  - AIM: To explore the possible mechanisms underlying the positive inotropic effect
      of MCI-154. METHODS: Skinned fibers with disrupted or preserved sarcoplasmic
      reticulum (SR) were prepared by saponin 500 or 50 mg.L-1. The tension-pCa
      relationship and pCa50 of saponin (500 mg.L-1)-skinned fibers were taken as the
      indices of Ca2+ sensitivity of contractile proteins. The amplitude of caffeine
      induced contracture was an index of Ca2+ release from SR in saponin (50 mg.L-1)
      skinned fibers. RESULTS: 1) MCI-154 (0.1 mmol.L-1) showed a Ca2+ sensitizing
      effect on contractile proteins. The pCa50 was increased to 5.84 (5.54-6.14)
      compared with control value 5.54 (5.30-5.79) (P < 0.01, n = 8). Hill coefficient
      n was decreased by 0.29 (P < 0.01, n = 8); 2) No contracture was produced by MCI
      154 in preparations with preserved SR. Caffeine-induced contracture before and
      after MCI-154 treatment were not changed (P > 0.05, n = 4). CONCLUSION: MCI-154
      directly enhances the Ca2+ sensitivity of contractile protein but has little
      effect on Ca2+ release from SR in rat skinned cardiac fibers.

PMID- 10072941
TI  - Altered alpha 1-adrenoceptor subtypes mediated cardiac function after treatment
      of propranolol to rats.
AB  - AIM: To study inotropic and chronotropic effects mediated by alpha 1A- and alpha
      1B-adrenoceptors after 5-d propranolol (Pro) treatment. METHODS: The positive
      inotropic and chronotropic effects mediated by alpha 1A and alpha 1B subtypes
      were determined on isolated left ventricular papillary muscles and right atrium
      in Pro- and NaCl-treated rats. RESULTS: The basic contractility of papillary
      muscles induced by phenylephrine (Phe) was 90 +/- 18 mg in Pro-treated rats and
      53 +/- 17 mg in control group (P < 0.05). The increment on force of contraction
      was 20 +/- 12 mg in Pro-pretreated rats and 5 +/- 5 mg in NaCl-treated rats (P <
      0.05). After preincubated with chloroethylclonidine, the increment on force of
      contraction was reduced in Pro-treated rats, but was not much changed in control
      group. Phe in presence of 5-methylurapidil induced positive inotropic effect with
      13 +/- 5 mg in Pro-treated group, but not in NaCl-treated rats. Under the normal
      and the inhibited cardiac state, the maximal increment in beat rate mediated by
      alpha 1B showed no difference between the Pro-treated and NaCl-treated rats.
      CONCLUSION: After chronic treatment of Pro, alpha 1-adrenoceptor-mediated
      positive inotropic effect in rat heart was improved, which was mainly induced by
      stimulation of alpha 1B when beta-adrenoceptors were blocked.

PMID- 10072942
TI  - Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig
      kidney by some bioflavonoids and triterpenoids.
AB  - AIM: To study the inhibitory effect of some bioflavonoids and triterpenoids on 11
      beta-hydroxysteroid dehydrogenase (11 beta-OHSD) from guinea pig kidney. METHOD:
      The 11 beta-OHSD of kidney cortex microsomes in addition of cortisol was
      incubated in the presence of NADP, Triton DF-18, and the test compounds at 37
      degrees C for 1 h. The enzyme activity was assayed by measuring the rate of
      conversion of cortisol to cortisone eluted with HPLC gradient analysis. RESULTS:
      The IC50 (95% confidence limits) values of glycyrrhizic acid, naringenin,
      fisetin, emodin were 254 (202-320), 336 (270-418), 470 (392-564), and 527 (425
      653) mumol.L-1, respectively. The inhibitory effect of oleanolic acid was 2-fold
      stronger than that of astramembranin I. The mode of action of naringenin was
      competitive inhibition. CONCLUSION: The test compounds inhibited the 11 beta-OHSD
      in kidney cortex with different potencies as glycyrrhizic acid did.

PMID- 10072943
TI  - Effects of cycloprotobuxine-A on atrial fibrillation.
AB  - AIM: To study the effects of cycloprotobuxine-A (Cyc-A) on atrial fibrillation.
      METHODS: Atrial fibrillations in vivo and in vitro were induced by arrhythmogenic
      drugs. Action potentials were measured by the standard microelectrode technique.
      RESULTS: Cyc-A, similar to or slightly stronger than amiodarone (Ami), decreased
      incidences of atrial fibrillation elicited by CaCl2-acetylcholine in mice and
      increased doses of aconitine, ouabain, or adrenaline to elicit atrial
      fibrillation in isolated guinea pig atria. Cyc-A 0.3-100 mumol.L-1 decreased the
      normal automaticity and 0.3-30 mumol.L-1 attenuated or almost abolished the
      isoprenaline-induced abnormal increase in automaticity in sinus nodal cells. In
      isolated left atria, Cyc-A 0.3-30 mumol.L-1 inhibited the abnormal rhythmic
      activity elicited by adrenaline, prolonged action potential duration (APD) and
      effective refractory period, and reduced excitability. At 3-30 mumol.L-1, Cyc-A
      also decreased the maximal velocity of depolarization (Vmax). Cyc-A antagonized
      the acetylcholine-induced shortening of APD. These electrophysiologic effects
      were similar to those of amiodarone, but Ami did not affect the Vmax. CONCLUSION:
      Cyc-A produces a protective effect against experimental atrial fibrillation via a
      prolongation of repolarization, a decease of automaticity, and an inhibition of
      excitability.

PMID- 10072944
TI  - Effects of praeruptorine C on the intracellular free calcium in normal and
      hypertrophied rat ventricular myocytes.
AB  - AIM: To study the intracellular free calcium ([Ca2+]i) in normal and hypertrophic
      left ventricular myocytes isolated from adult rat hearts and the effects of
      praeruptorine C (Pra-C) on them. METHODS: [Ca2+]i of single myocyte was measured
      with Fura 2-AM. RESULTS: The resting [Ca2+]i was 87 +/- 4 nmol.L-1 in normal left
      ventricular myocytes, 123 +/- 7 nmol.L-1 in hypertrophied myocytes. After
      exposure to KCl (20, 40, and 60 mmol.L-1), the [Ca2+]i were increased by 66%,
      141%, and 268% in normal myocytes, and 77%, 185%, and 243% in hypertrophic
      myocytes, respectively. Pra-C (1, 10, and 100 mumol.L-1) concentration
      dependently inhibited the [Ca2+]i elevation caused by KCl (35 mmol.L-1) or
      norepinephrine (20 mumol.L-1) in both normal and hypertrophied myocytes. All of
      the effects of Pra-C were similar to that of nifedipine. CONCLUSION: [Ca2+]i of
      hypertrophied myocytes was higher than that of normal ones and Pra-C decrease the
      [Ca2+]i elevation in left ventricular myocytes resulted from its calcium channel
      blockade.

PMID- 10072945
TI  - Muscarinic stimulation of calcium/calmodulin-dependent protein kinase II in
      isolated rat pancreatic acini.
AB  - AIM: To study whether M3 receptor occupation would lead to activation of
      calcium/calmodulin-dependent protein kinase II (CaM kinase II). METHODS: In this
      study, we isolated rat pancreatic acini by collagenase digestion; measured the
      Ca2+/calmodulin-independent activity of autophosphorylated form of the CaM kinase
      II both before and after stimulation of the acini with muscarinic secretagogue
      bethanechol (Bet). RESULTS: Bet stimulated the activation of, or generation of
      Ca(2+)-independent activity of, this kinase, in a concentration (0.0001-1 mmol.L
      1) and time (5-300 s)-dependent manner; with Bet of 100 mumol.L-1, Ca(2+)
      independent activity increased from an unstimulated level of 4.5 +/- 0.3 (n = 4)
      to 8.9 +/- 1.3 (n = 4, P < 0.05) at 5 s. Another Ca2+ mobilizing secretagogue
      cholecystokinin (CCK) also activated the kinase; at 1 mumol.L-1, CCK increased
      Ca(2+)-independent kinase activity to 12.9 +/- 0.5 (n = 6, P < 0.05). Vasoactive
      intestinal peptide (VIP) at 1 mumol.L-1 did not produce significant Ca(2+)
      independent kinase activity (from control 3.90 +/- 0.28 to 4.53 +/- 0.47, n = 6,
      P > 0.05). Atropine completely blocked Bet activation of the kinase. CONCLUSION:
      CaM kinase II plays a pivotal role in digestive enzyme secretion, especially
      during the initial phase of amylase secretion.

PMID- 10072946
TI  - Immunosurgical studies on cytological and cytogenetic toxicity analysis of rat
      blastocysts after in vivo exposure to cyclophosphamide.
AB  - AIM: To establish immunosurgery and indices of cytogenetic assessment for
      blastocyst and its inner cell mass (ICM), and to evaluate the toxic effects after
      in vivo exposure to cyclophosphamide. METHODS: Modified immunosurgery was
      established by preparation of rabbit-anti-rat spleen antiserum and induction of
      diluted rat mixed serum as complement. Pregnant rats on d 3 of gestation were
      injected i.p. cyclophosphamide (10, 20, and 40 mg.kg-1). On d 4, immunosurgery
      was performed on rat blastocysts. The cell number and the micronuclei of
      blastocyst and ICM were evaluated respectively. RESULTS: In the cyclophosphamide
      treated rats, decreases of cell number (35 +/- 3, 32 +/- 1, 30 +/- 1, and 14 +/-
      2, 11 +/- 1, 9 +/- 2) and increases of frequency of micronuclei (1.81%, 2.27%,
      3.14%, and 2.53%, 2.98%, 4.75%) in blastocysts and ICM were observed in a dose
      related manner. The changes of blastocyst were, however, not parallel to those of
      ICM which were more serious. CONCLUSION: Modified immunosurgery, an objective and
      elegant technique, was used on rat blastocysts. In vivo could cyclophosphamide
      injured ICM more than blastocysts.

PMID- 10072947
TI  - Cyclosporine inhibited calcium-mediated apoptosis of HL-60 cells.
AB  - AIM: To study the effects of cyclosporine (Cyc) on apoptosis of HL-60 cells.
      METHODS: Apoptotic cells induced by harringtonine (Har), camptothecin (Cam), or
      calcimycin (Cal), thapsigargin (Tha) were identified with DNA electrophoresis,
      morphology, and flow cytometry. Relative [Ca2+]i alteration of apoptotic HL-60
      cells were determined with flow cytometry. RESULTS: Cal 1 mg.L-1 or Tha 0.5 mg.L
      1 induced apoptosis of HL-60 cells. This effect was inhibited by nontoxic
      concentration of Cyc 1 mg.L-1. Cyc did not inhibit Har- or Cam-induced apoptosis
      of HL-60 cells. Both Cal and Tha increased intracellular calcium, whereas Har or
      Cam did not. CONCLUSION: Cyc inhibited apoptosis only induced by calcium
      increasement in HL-60 cells. The mechanism of apoptosis induced by Cal or Tha was
      different from that by Har or Cam.

PMID- 10072948
TI  - Estrogens induce apoptosis in mouse peritoneal macrophages.
AB  - AIM: To study whether estrogen might induce apoptosis in mouse peritoneal
      macrophages (MPM). METHOD: The MPM were isolated and incubated in culture medium
      containing 17-beta-estradiol, estrone, or equal volume of 100% ethanol as
      control. DNA fragmentation was visualized by agarose gel electrophoresis.
      RESULTS: 17-beta-Estradiol 0.01-1 mumol.L-1 or estrone 10-20 mumol.L-1 elicited
      typical morphological apoptosis and DNA fragmentation in a concentration
      dependent manner in MPM. Staurosporine (Sta) 0.01 mumol.L-1, cycloheximide (Cyc)
      1 mg.L-1, and tamoxifen (Tam) 10 mumol.L-1 inhibited the DNA fragmentation
      induced by 17-beta-estradiol 1 mumol.L-1 or estrone 20 mumol.L-1. CONCLUSION:
      Estradiol and estrone induced apoptosis in MPM.

PMID- 10072949
TI  - Effect of tripterine on collagen-induced arthritis in rats.
AB  - AIM: To study the therapeutic effect of tripterine (Tri) on collagen-induced
      arthritis (CIA). METHODS: Collagen type II (Col) 1.5 mg was injected
      intradermally to induce CIA in rats. Hind paw volumes of rats were measured with
      a water displacement method. The serum anti-collagen antibody was measured by an
      enzyme-linked immunosorbent assay. Delayed hypersensitivity was reflected by skin
      response to Col. Interleukin-1 (IL-1) and interleukin-2 (IL-2) activities were
      evaluated by [3H]TdR uptake. Joint was evaluated histologically. RESULTS: Tri 15
      and 30 mg.kg-1.d-1 given i.g. to rats 3 d after the first sign of arthritis
      reduced inflammatory swelling, suppressed humoral and skin response to Col,
      inhibited IL-2 and IL-1 production, reduced pathological progression of joint.
      CONCLUSION: Tri has a therapeutic effect on CIA.

PMID- 10072950
TI  - Antipsoriatic, anti-inflammatory, and analgesic effects of an extract of red
      propolis.
AB  - AIM: To study the antipsoriatic, anti-inflammatory, and analgesic effects of
      ethanolic extract of red propolis. METHODS AND RESULTS: This extract induced the
      formation of granular layer in the mouse tail test used as a model of psoriasis.
      Propolis 50 mg.kg-1 i.g. showed anti-inflammatory activity in the cotton-pellet
      granuloma assay in rats, in croton oil-induced edema in mice at a dose of 25%
      (2.5 microL), and in the peritoneal capillary permeability test in mice at a dose
      of 10 mg.kg-1. The extract (25 mg.kg-1 i.g.) showed analgesic effect in the model
      of acetic acid-induced writhings, whereas 40 mg.kg-1 was effective in the hot
      plate test in mice. CONCLUSION: Anti-inflammatory, analgesic, and antipsoriatric
      properties of Cuban red propolis were evident.

PMID- 10072951
TI  - Effect of sodium glycyrrhetinate on chemical peritonitis in rats.
AB  - AIM: To study the anti-inflammatory mechanisms of sodium glycyrrhetinate (SG).
      METHODS: Rat chemical peritonitis was used. The protein content and prostaglandin
      E2 (PGE2) content in exudate were measured by Folin-phenol assay and RIA,
      respectively. SOD activity in neutrophils (Neu) was determined by pyrogallol-NBT
      colorimetry. cAMP content in Neu was detected by competitive protein binding
      assay. RESULTS: In peritonitis caused by histamine, SG 10-20 mg.kg-1 i.m. reduced
      exudate volume and Neu counts, and 5-20 mg.kg-1 i.m. lowered the protein content
      in exudate. In peritonitis induced by carrageenan, SG 20 mg.kg-1 i.m. reduced
      exudate volume, Neu counts, protein content and PGE2 content in exudate,
      increased SOD activity in Neu, but did not affect beta-glucuronidase release from
      Neu. In peritonitis induced by arachidonic acid, SG 20 mg.kg-1 i.m. reduced Neu
      counts, protein content, and PGE2 content in exudate, and attenuated the
      reduction of cAMP level in Neu. CONCLUSION: SG exerts its anti-inflammatory
      action by lowering permeability of capillaries in inflammatory site, inhibiting
      Neu emigration and PGE2 biosynthesis, and scavenging oxygen free radicals.

PMID- 10072952
TI  - Quercetin induced apoptosis in human leukemia HL-60 cells.
AB  - AIM: To examine whether quercetin (Que) might induce apoptosis in human leukemia
      HL-60 cells. METHODS: DNA fragmentation was visualized by agarose gel
      electrophoresis. Inhibition of proliferation was measured with a colorimetric MTT
      assay. The DNA degradation was determined using flow cytometry, and the
      microscopic changes were observed by an electron microscope. RESULTS: Que 15-120
      mumol.L-1 elicited typical apoptosis morphological changes including condensed
      chromatin, nuclear fragmentation, and reduction in volume. DNA fragmentation and
      DNA degradation in a concentration-dependent manner in HL-60 cells. Que inhibited
      HL-60 cell proliferation. The values of IC50 and 95% confidence limits were 43
      (30-61) mumol.L-1 after 48-h treatment with Que. CONCLUSION: Que induced
      apoptosis in HL-60 cells.

PMID- 10072953
TI  - Monoclonal antibody 3F3 against conformational epitope of Torpedo
      acetylcholinesterase.
AB  - AIM: To study the type of epitope of native Torpedo acetylcholinesterase (AChE)
      directed by its monoclonal antibody (McAb) 3F3. METHODS: Enzyme-linked
      immunosorbent assay (ELISA) was used for the assay of the reaction between
      antigen and antibody. RESULTS: McAb 3F3 immunoreacted well with the native AChE,
      but not with the reduced- and alkylated-AChE (RA-AChE) at all. Soman did not
      interfere the binding of 3F3 with AChE molecule. The synthesized 24-peptide
      containing the active serine residue of the AChE active center did not react with
      McAb 3F3. CONCLUSION: 3F3 is a monoclonal antibody against the conformational
      epitope of Torpedo AChE active center, but dose not occupy the active serine
      residue of the enzyme.

PMID- 10072954
TI  - [Effects of fructus cnidii coumarins compared with nilestriol on osteoporosis in
      ovariectomized rats].
AB  - AIM: To compare the total coumarins from dried fruits of Cnidium monnieri (TCCM)
      and nilestriol (Nil) against osteoporosis. METHODS: SD rats (40, female, 3-month
      old) were randomly divided into basal control, age control, ovariectomized (Ova),
      Ova + TCCM 67 mg.kg-1, Ova + TCCM 200 mg.kg-1, 6 times a week, and Ova + Nil 1
      mg.kg-1, i.g. once a week. After 12 wk, sections (20 microns) of proximal tibiae
      were examined histologically. RESULTS: Ova reduced markedly the trabecular bone
      mass due to bone resorption excessed bone formation (% Tb. Ar -59%). Treatment
      with TCCM 67 mg.kg-1 partly suppressed bone turnover, but did not inhibit bone
      loss in Ova rats (% Tb.Ar -43%). Treatment with TCCM 200 mg.kg-1 and Nil 1 mg.kg
      1 increased the trabecular area (% Tb. Ar +100% and +274%). CONCLUSION: Nil was
      more potent than TCCM in protecting against osteoporosis in Ova rats via
      supression of bone turnover.

PMID- 10072955
TI  - Antagonistic effects of trifluoperazine, imipramine, and chlorpromazine against
      acetylcholine-induced contractions in isolated rat uterus.
AB  - AIM: To examine the effects and affinity of some phenothizines (trifluoperazine,
      Tri and chlorpromazine, Chl) and antidepressant (imipramine, Imi) drugs on
      acetylcholine (ACh)-induced uterine contraction. METHODS: Isotonic contractions
      of rat uterine strips were recorded. ACh was administrated to induce maximal
      contraction before exchange of nutrient solution. ACh was added 5 min after the
      testing drugs. The nutrient solution was exchanged 4 times after each agonist
      (ACh or other agents) to produce maximal contraction. RESULTS: Atropine (Atr,
      0.029-2.9 mumol.L-1), 4-DAMP (3.6-360 nmol.L-1), pirenzepine (Pir, 0.23-23.5
      mumol.L-1), and AF-DX 116 (0.7-35.6 mumol.L-1) competitively antagonized the
      muscular uterine concentration induced by ACh (0.068-36068 mumol.L-1). The Schild
      plot was linear (r = 1.00). The pKB and slopes values (95% confidence limits)
      were 9.28 +/- 0.12 and 1.00 +/- 0.10 to Atr, 9.06 +/- 0.10 and 1.10 +/- 0.08 to 4
      DAMP, 7.03 +/- 0.15 and 0.99 +/- 0.12 to Pir, and 5.60 +/- 0.08 and 1.00 +/- 0.19
      to AF-DX 116. Tri 0.01-2 mumol.L-1 (pKB = 8.39 +/- 0.04) and Imi 94-940 nmol.L-1
      (pKB = 7.21 +/- 0.10) produced also a competitive antagonism of the muscular
      uterine contraction induced by ACh (r = 1.00), but the slope was only 0.60 +/-
      0.03 to Tri or 0.83 +/- 0.16 to Imi. Chl 2.8-5.6 mumol.L-1 produced a weak
      antagonism on amplitude of muscular contraction induced by the cholinomimetic.
      CONCLUSION: The muscarinic receptors on uterus behaved as M3 subtype. Tri and
      Imi, but not Chl, were competitive antagonist of muscarinic receptors of uterus.
      Imi behaved a simple competitive antagonist at a single site on myometrium, but
      Tri was not a simple competitive agent at a single site.

PMID- 10072956
TI  - Vasodilative properties of BPDZ 79, a new potassium channel opener, in isolated
      aorta.
AB  - AIM: To compare the effect of a novel potassium channel opener 3-(1',2',2'
      trimethylpropyl)amine-4H-pyrido (2,3-e)-1,2,4-thiadiazine, 1-dioxide (BPDZ 79),
      with diazoxide on aorta. METHODS: Muscle tension of rat aorta was compared with
      adjacent aortic rings without endothelium. One ring was precontracted with KCl 80
      mmol.L-1. Three rings were precontracted with KCl 80 mmol.L-1, and two of them
      were incubated with glibenclamide (0, 1, and 10 mumol.L-1). 86Rb outflow from rat
      aorta was measured in the presence of glibenclamide 10 mumol.L-1. RESULTS: BPDZ
      79 and diazoxide provoked concentration-dependent and endothelium-independent
      relaxation of the vasoconstriction evoked by KCl 30 mmol.L-1, but not by 80
      mmol.L-1. BPDZ 79 showed more potent vasorelaxation and 86Rb outflow than
      diazoxide. After incubation with glibenclamide (1 and 10 mumol.L-1), an inhibitor
      of the ATP-sensitive K+ channels, the relaxation induced by BPDZ 79 and diazoxide
      were decreased with the same pattern. CONCLUSION: BPDZ 79 is a potent vasodilator
      by opening potassium channels.

PMID- 10072957
TI  - Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in
      spontaneously hypertensive rat.
AB  - AIM: To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of
      metoprolol stereoisomers, and compare their inhibitory effects on cardiovascular
      system in the spontaneously hypertensive rats (SHR). METHODS: The drug
      concentration in plasma was measured by the reversed phase HPLC and the drug
      effects were recorded by polygraph. The pharmacokinetic parameters and the PK-PD
      model parameters were calculated. RESULTS: The plasma concentration-time profiles
      were adequately described by two-compartment model. Differences of Vd between (+)
      Met and (-)-Met were found. The relationships between effects and concentration
      of effect compartment were represented by the sigmoid-Emax model. The Css50 of
      Vmax, dp/dtmax, and HR inhibitory effects of (+)-Met were larger than those of (
      )-Met. CONCLUSION: Stereo-selective drug distribution and different potencies of
      the inhibitory effects of (+)-Met and (-)-Met existed in SHR.

PMID- 10072958
TI  - Pharmacokinetics of bendazac lysine in 10 Chinese young men.
AB  - AIM: To compare the pharmacokinetics of domestic and imported tablets of bendazao
      lysine (BL). METHODS: A single oral dose of 500 mg BL of this 2 kinds of tablets
      was given to 10 Chinese volunteers of Han nationality in a randomized crossover
      study. Plasma levels were determined with HPLC-UV method. Data were analyzed
      automatically by using a CAPP program on microcomputer. RESULTS: The plasma
      concentration-time curve was fitted to 2-compartment open model, and the major
      pharmacokinetic parameters of domestic and imported BL tablets were shown
      respectively as following: Cmax 66 +/- 16 and 65 +/- 8 mg.L-1; Tmax 0.98 +/- 0.22
      and 0.98 +/- 0.21 h; T1/2 beta 6.2 +/- 1.8 and 6.2 +/- 1.7 h; AUC 335 +/- 47 and
      337 +/- 58 mg.h.L-1. There was no significant difference between domestic and
      imported tablets. The bioavailability of the domestic vs that of the imported
      tablet was 99 +/- 12%. The unchanged BL in urine were about 5.4% and 5.6%
      respectively of the dosage in 24 h after a single oral dose. CONCLUSION: The two
      kinds of tablets had the same biological effects.

PMID- 10072959
TI  - Rapid detoxification of heroin dependence by buprenorphine.
AB  - AIM: To evaluate the clinical efficacy of buprenorphine (Bup) in treatment of
      acute heroin withdrawal. METHODS: Bup was given sublingually daily to 60 cases of
      heroin addicts in 3 groups: low, medium, and high doses. Withdrawal signs and
      symptoms of heroin were rated by Clinical Institute Narcotic Assessment. Craving
      for heroin during detoxification was assessed by Visual Analogue Scale. The side
      effects of Bup was assessed by Treatment Emergent Symptom Scale. RESULTS: The
      mean daily consumption of Bup in low, medium, and high group was 2.0, 2.9, and
      3.6 mg, respectively. Bup not only suppressed objective signs and withdrawal
      symptoms for heroin withdrawal, but also reduced the duration for heroin
      detoxification over 7-8 d. CONCLUSION: Bup is an effective and rapid
      detoxification agent with fewer side effects for treatment of acute heroin
      withdrawal.

PMID- 10072960
TI  - Characterization of [125I]RTI-121 binding to dopamine transporter in vitro.
AB  - AIM: To characterize the binding of [125I]3 beta-(4-iodophenyl) tropane-2 beta
      carboxylic acid isopropyl ester (RTI-121) to the dopamine transporter (DAT) under
      physiologically relevant conditions. METHODS: [125I]RTI-121 was used to label the
      DAT on fresh rat striatum synaptosomal membranes in artificial cerebrospinal
      fluid (ACSF) at 37 degrees C. RESULTS: [125I]RTI-121 binding reached equilibrium
      within 3 min and remained at its plateau value for at least 9 min. The data from
      kinetic, saturation, and competition studies supported a one-site model for the
      binding of [125I]RTI-121 to the DAT. Various DAT blockers (oocaine, GBR12935, and
      BTCP) and substrates (dopamine and d-amphetamine) competitively inhibited the
      binding of [125I]RTI-121. Compared with NaPhos-KCl-NaCl assay buffer, ACSF
      containing Ca2+ and Mg2+ markedly increased the IC50 of DAT blockers for
      inhibiting [125I]RTI-121 binding with less effect on that of substrates. Various
      D2 receptor ligands (pergolide, quinirole, sulpiride, and l-stepholidine) had no
      direct effect on the binding of [125I]RTI-121. CONCLUSION: [125I]RTI-121 binding
      under physiologically relevant conditions fulfills the basic criteria for DAT
      binding assay.

PMID- 10072961
TI  - Intrahippocampal infusion of interleukin-6 impairs avoidance learning in rats.
AB  - AIM: To study the effect of intrahippocampal infusion of interleukin-6 (IL-6) on
      active avoidance in rats and the possible involvement of nitric oxide (NO).
      METHODS: Using a shuttle-box model, the effects of bilaterally intrahippocampal
      infusion of IL-6 3.2, 16, and 80 ng as well as sodium nitroprusside (SNP) 400 ng
      on active avoidance were studied on d 8 after administration. The levels of
      nitrite as an index of NO in the hippocampus were detected using a fluorometric
      assay 24 h after infusion of IL-6 3.2 or 80 ng. RESULTS: IL-6 16 and 80 ng
      impaired the acquisition performance of active avoidance by prolonging the
      latency of avoidance in training, but not the retention performance in testing.
      IL-680 ng and SNP 400 ng also resulted in a marked impairment in acquisition
      performances by decreasing the rate of avoidance, but not in retention
      performances. IL-680 ng markedly elevated the nitrite levels from 10.6 +/- 0.7 in
      control rats to 13.6 +/- 2.0 (nmol/g wet wt) (P < 0.01). IL-6 3.2 ng had no
      effect on active avoidance nor on nitrite levels. CONCLUSION: Intrahippocampal
      infusion of IL-6 impaired learning acquisition of active avoidance in rats.

PMID- 10072962
TI  - Adrenoceptor agonists inhibit calcium-dependent potentials in rat stellate
      ganglion neurons.
AB  - AIM: To study the effects of adrenoceptor agonists on the stellate ganglion
      neurons. METHODS: Intracellular recordings were made from neurons of the isolated
      rat stellate ganglia. RESULTS: Noradrenaline and clonidine (10-30 mumol.L-1)
      reversibly depressed 3 types of calcium-dependent potentials, namely, the action
      potential shoulder; the spike after-hyperpolarization; the Ca2+ spike evoked in
      Krebs' solution containing TTX and TEA and fast excitatory postsynaptic potential
      (f-EPSP). CONCLUSION: The adrenoceptor agonists inhibitied the 3 calcium
      dependent potentials; f-EPSP was inhibited by reducing Ca2+ influx at presynaptic
      site in population of neurons.

PMID- 10072963
TI  - Interaction models of 3-methylfentanyl derivatives with mu opioid receptors.
AB  - AIM: To study the interaction model of 3-methylfentanyl derivatives with mu
      opioid receptor. METHODS: After a systematic conformational search, a three
      dimensional quantitative structure-activity relationship study was carried out
      with comparative molecular field analysis (CoMFA). RESULTS: 1) The 6 CoMFA models
      had good predictive values and each model corresponded to the minimum-energy
      conformations of 13 compounds studied; 2) The important geometric parameters of
      mu pharmacophore d1 (A), d2 (A), d3 (A), d4 (A), d5 (A), and d6 (A) were 5.2,
      5.4, 4.9, 10.6, 10.2, and 5.8 in Model A; 5.2, 6.5, 3.6, 10.6, 11.6, and 5.8 in
      Model B; 5.2, 4.6, 4.9, 11.6, 9.2, and 6.5 in Model C; 5.2, 5.4, 4.9, 10.5, 10.3,
      and 5.8 in Model D; 3.6, 5.4, 4.9, 5.7, 7.5, and 5.7 in Model E; 5.2, 4.7, 4.9,
      11.2, 9.5, and 6.4 in Model F, respectively. CONCLUSIONS: The several bioactive
      conformations of fentanyl analogs possibly existed and did not need to be the
      absolute minimum-energy conformation, each of which was involved in the
      interaction with mu opioid receptor.

PMID- 10072964
TI  - Tumor necrosis factor mediated release of platelet-derived growth factor from
      bovine cerebral microvascular endothelial cells.
AB  - AIM: To study the effect of tumor necrosis factor (TNF) on platelet-derived
      growth factor (PDGF) release from bovine cerebral microvascular endothelial cells
      (BCMEC), and the protection of drugs on proliferation of bovine cerebral
      microvascular smooth muscle cells (BCMSMC). METHODS: BCMEC and BCMSMC were
      cultured in vitro. Effects of TNF on PDGF release from BCMEC were investigated by
      crystal violet assay. RESULTS: TNF did not promote the proliferation of BCMSMC
      directly. But the postculture medium of BCMEC stimulated by TNF promoted the
      proliferation of BCMSMC in a concentration (5-20 micrograms.L-1)-dependent
      manner, and the mitogenic activity was neutralized by antibody to PDGF. The
      BCMSMC proliferation was increased 34 +/- 4% over control by TNF (20 micrograms.L
      1). Imperatorin (Imp), iso-imperatorin (iso-Imp), and 6-(alpha, alpha
      phenylacetylpiperazinyl) phenyl-5-methyl-4, 5-dihydro-3 (2H)-pyridazinone (PMDP)
      1-100 mumol.L-1 did not affect the PDGF release from BCMEC stimulated by TNF, but
      inhibited the BCMSMC proliferation promoted by PDGF concentration-dependently.
      CONCLUSION: TNF promoted PDGF release from BCMEC. The proliferation of BCMSMC
      stimulated by TNF must be mediated by growth factor, such as PDGF. Imp, iso-Imp,
      PMDP inhibited proliferation of BCMSMC stimulated by PDGF.

PMID- 10072965
TI  - Inhibitory effects of nifedipine on DNA and protein synthesis in cultured cardiac
      nonmyocytes of neonatal rats.
AB  - AIM: To observe the inhibitory effects of nifedipine (Nif) on cardiac nonmyocytes
      growth and proliferation. METHODS: Using nonmyocytes in culture as a model,
      [3H]thymidine and [3H]leucine incorporation were measured. RESULTS: There was a
      significant decrease in cell number and in total cellular protein after 72-h
      exposure to Nif 1 mumol.L-1 in the presence of angiotensin II (Ang II). A 48-h
      exposure to 1, 10, 100, 1000 nmol.L-1 of Ang II caused a 19%, 35%, 46%, 48%
      increase in protein synthesis and 27%, 46%, 56%, 57% increase in DNA synthesis.
      Nif 1, 3, and 10 mumol.L-1 were able to reduce the Ang II 100 nmol.L-1-induced
      increase of protein synthesis and DNA synthesis. CONCLUSION: Nif had a direct
      inhibitory action on the growth of nonmyocytes, which was related to the
      regression of cardical hypertrophy.

PMID- 10072966
TI  - Effects of captopril and enalaprilat on intracellular Ca2+, Na+ contents and pH
      in hypoxic and reoxygenated cardiomyocytes.
AB  - AIM: To study the mechanisms of captopril (Cap) and enalaprilat (Ena) protective
      effects on hypoxic and reoxygenated cardiac myocytes. METHODS: Using fluorescent
      probes Fura 2-AM, BCECF/AM, SBFI/AM combined with computer image processing
      techniques to measure intracellular ion concentrations. RESULTS: [Ca2+]i (165 +/-
      8 nmol.L-1) and [Na+]i (9.2 +/- 0.8 mmol.L-1) were higher but [pH]i (6.7 +/- 0.3)
      was lower in hypoxic and reoxygenated myocytes (196 +/- 14 nmol.L-1, 9.3 +/- 1.3
      mmol.L-1, 6.61 +/- 0.19, respectively) than in normal ones. Cap and Ena reduced
      [Ca2+]i (149 +/- 11 and 152 +/- 10 nmol.L-1 respectively) and intracellular
      acidosis (7.11 +/- 0.22 and 7.2 +/- 0.4, respectively) during hypoxia. Cap also
      decreased [Na+]i in hypoxic myocytes (8.1 +/- 0.9 mmol.L-1). During
      reoxygenation, Cap decreased [Ca2+]i and [Na+]i but Ena had no significant effect
      on them. Cap or Ena had no additive effect when combined with verapamil (Ver).
      CONCLUSION: Cap and Ena protected hypoxic and reoxygenated cardiomyocytes, but
      the mechanisms were not the same.

PMID- 10072967
TI  - Effects of tetrahydroprotoberberines on dopamine D2 receptors in ventral
      tegmental area of rat.
AB  - AIM: To compare the actions of tetrahydroprotoberberines (THPB) on dopamine (DA)
      D2 receptors in the ventral tegmental area (VTA) of rat. METHODS: Extracellular
      single unit recording technique was used in i.v. gallamine-paralyzed rats.
      RESULTS: Eleven THPB analogs tested completely attenuated the apomorphine (Apo,
      20 micrograms.kg-1)-induced inhibition on VTA DA cell firing activity. The OH
      group on C2 at THPB was linked with the reversal of Apo-induced inhibition. Their
      reversal potencies (ED50, microgram.kg-1) for D2 receptors were: THPB-143 (5.6) >
      SPD (8.5) > Iso (17.0) > THP (33) > THB (48) > THPB-18 (66) > THPB-1 (179) > THPB
      19 (408) > THPB-126 (510) > THPB-104 (1019) > THPB-10 (4815). CONCLUSION: Among
      these 11 THPB, the 2-hydroxyl-THPB (THPB-143) showed the strongest antagonistic
      action on D2 receptors.

PMID- 10072968
TI  - Effects of clonidine on myocardial beta-adrenergic receptor-adenyl cyclase-cAMP
      system after scalds in rats.
AB  - AIM: To study the role of clonidine (Clo) on the myocardial beta-adrenergic
      receptor (beta-AR)-adenyl cyclase (AC)-cAMP system after the scalds in rats.
      METHODS: A 30% skin-full-thickness scald was produced by immersing rats in 95
      degrees C water for 9 s. Clo 0.1-3.0 mg.kg-1 was injected i.p. to rats at 30 min
      before scalds, yohimbine (Yoh) 0.05 mg.kg-1 or prazosin (Pra) 0.03 mg.kg-1 to
      rats at 30 min before i.p. Clo. beta-AR density and affinity, AC activity,
      phosphoric diester hydrolases (PDH) activity, and cAMP content were determined
      with radioreceptor assay, indirect method, enzymeradiochemical assay, and
      radioimmunoassay, respectively. RESULTS: Clo inhibited the decrease of the
      myocardial beta-AR density, the attenuation of AC activity, and the reduction of
      cAMP content at 12 h after the scalds. Yoh partially reversed the effects of Clo
      on the three parameters. But Pra did not. CONCLUSION: Clo reversed the changes of
      the myocardial beta-AR-AC-cAMP system resulted from the scalds in rats.

PMID- 10072969
TI  - Antioxidative activity of 4-oxy- and 4-hydroxy-nitroxides in tissues and
      erythrocytes from rats.
AB  - AIM: To compare the activities of antioxidation of 4-oxy- and 4-hydroxy
      nitroxides in tissues and RBC from rats. METHODS: The homogenates of liver,
      heart, and kidneys of rats were used to determine malondialdehyde (MDA) formation
      using TBA colorimetric method. H2O2-caused hemolysis was measured
      spectrometrically. Superoxide anion from zymosan-stimulated neutrophils of rats
      was assayed by NBT reduction method. RESULTS: Nitroxide free radicals OTMPO and
      HTMPO inhibited MDA generation caused by .OH generation system (MIC 10.5 and 21
      mumol.L-1, respectively), antagonized hemolysis induced by H2O2 (MIC: 338 and 168
      mumol.L-1, respectively), but did not affect O2- formation from activated
      neutrophils. 1-Hydroxyl compounds OTMPOH and HTMPOH possessed similarly potent
      antilipoperoxidative activities. But nonfree radical OTMP and HTMP had no effect
      on peroxidation of tissues. CONCLUSION: Nitroxides exert their
      antilipoperoxidative effect by specifically scavenging .OH free radicals in
      biological system. Trapping of .OH free radicals by nitroxides is not by
      reduction of NO. group in nitroxides. Both NO. group and NOH group are essential
      active groups.

PMID- 10072970
TI  - Mepyramine inhibits platelet activating factor-induced rabbit platelet
      aggregation: role of intracellular histamine.
AB  - AIM: To study the possible role of intracellular histamine (HA) in platelet
      activating factor (PAF)-induced platelet activation. METHODS: Washed rabbit
      platelet suspension was used to test the inhibitory effect of mepyramine (Mep, an
      H1 receptor antagonist) on PAF-induced platelet aggregation. The thromboxane B2
      (TXB2) generation was measured by radioimmunoassay and the intracellular calcium
      ([Ca2+]i) concentration was determined by the specific fluorescence indicator
      Fura-2. RESULTS: Mep > 100 mumol.L-1 generated a concentration-dependent
      inhibition on PAF-induced aggregation, with an IC50 value of 162 (95% confidence
      limits: 114-232 mumol.L-1). Cimetidine, an H2 receptor antagonist, even up to 400
      mumol.L-1 had no effect on it. Exogenous HA (10 mumol.L-1) and H1 receptor
      agonist, 2-thiazolylethylamine had no energetic effect. alpha
      Fluoromethylhistidine, an inhibitor of histidine decarboxylase, did not inhibit
      platelet responses. However, in platelets permeabilized with saponin (8-10 mg.L
      1), exogenous HA attenuated the inhibitory effect of Mep to about 50% at a
      concentration of 50 mumol.L-1. Preincubation of platelets with Mep (100 or 200
      mumol.L-1) resulted in an inhibition on TXB2 generation and [Ca2+]i elevation
      induced by PAF. CONCLUSION: Platelets activated by PAF is associated with an
      intracellular HA synthesis and release via a common pathway of TXB2 generation
      and the rise of [Ca2+]i.

PMID- 10072971
TI  - Histamine aggravated levothyroxine-induced cardiomyopathy in guinea pigs.
AB  - AIM: To study effects of histamine on cardiomyopathy. METHODS: Cardiomyopathy
      model was developed in guinea pig by i.p. levothyroxine 0.5 mg.kg-1.d-1 for 10 d.
      Langendroff's hearts were perfused. ECG and contractile force were recorded.
      Histamine (5 micrograms) was given by intra-aortic injection. Histamine content
      of coronary venous effluent was determined fluorometrically. RESULTS: Attack of
      histamine on cardiomyopathy was severer than that in normal hearts. Tachycardia
      was more prominent; atrioventricular conduction block occurred earlier; decrease
      in coronary flow was more marked. Uptakes of histamine were 37% in the model and
      19% in the normal hearts (P < 0.01). CONCLUSION: Histamine aggravated
      levothyroxine-cardiomyopathy.

PMID- 10072972
TI  - Staurosporine blocked normal cells at G1/S boundary.
AB  - AIM: To reveal the regulating difference of G1/S-phase transition between normal
      and tumor cells by using staurosporine, an unspecific kinase inhibitor. METHODS:
      Flow cytometry, Dot blot, kinase activity assay, and electrophoresis. RESULTS: A
      18-h treatment with staurosporine (5 micrograms.L-1) blocked normal cell line 2BS
      cells (normal human embryonic lung fibroblast, 5-20 passages) in G1 phase,
      decreased their thymidine kinase (TK) mRNA level and activity, and also
      dephosphorylated an intracellular 107 kDa protein. Meanwhile, all these effects
      in 2BS cells disappeared only by washing staurosporine away. Such kind of effects
      did not occur in tumor cell line BGC-823 cells (human stomach cancer cell).
      CONCLUSION: During the period of G1/S-phase transition, the kinases involved are
      more sensitive to staurosporine in normal cells than in tumor cells.

PMID- 10072973
TI  - Effects of dexamethasone and ibuprofen on LPS-induced gene expression of TNF
      alpha, IL-1 beta, and MIP-1 alpha in rat lung.
AB  - AIM: To study the kinetics of tumor necrosis factor alpha (TNF alpha),
      interleukine-1 (IL-1 beta), and macrophage inflammatory protein-1 alpha (MIP-1
      alpha) gene expression in rat lung after i.p. lipopolysaccharides (LPS) and the
      effect of dexamethasone (Dex) and ibuprofen (Ibu) on the cytokines gene
      expression. METHODS: The amount of Evans blue in lung was measured by
      fluorescence method. The mRNA levels of TNF alpha, IL-1 beta, and MIP-1 alpha in
      rat lung were assessed by slot blot analysis. RESULTS: The mRNA levels of TNF
      alpha, IL-1 beta, and MIP-1 alpha in rat lung after i.p. LPS increased in a dose
      dependent manner, and peaked at 2, 6, and 12 h, respectively. Both Dex 50 mg.kg-1
      and Ibu 90 mg.kg-1 injected at 1 h before i.p. LPS markedly decreased the content
      of Evans blue in lung at 1 h after i.p. LPS. After Dex or Ibu pretreatment, the
      peak levels of TNF alpha, IL-1 beta, and MIP-1 alpha mRNA decreased markedly
      compared with LPS alone. CONCLUSION: The gene expression of TNF alpha, IL-1 beta,
      and MIP-1 alpha in rat lung increased after i.p. LPS. Dex and Ibu prevented LPS
      induced lung injury through inhibiting the cytokines gene expression.

PMID- 10072974
TI  - alpha-Anordrin-induced apoptosis of leukemia K562 cells is not prevented by
      cicloheximide.
AB  - AIM: To study effect of protein synthesis inhibitor cicloheximide (Cic) on the
      apoptosis induced by alpha-anordrin (Ano) in leukemia K562 cells. METHODS:
      Morphological changes were observed by fluorescent microscopy. DNA content was
      measured by flow cytometry. DNA fragmentation was analyzed by agarose gel
      electrophoresis. RESULTS: Exposure of K562 cells to Ano 50 mumol.L-1 for 24 h
      induced apoptotic cell death. Cic 1 mumol.L-1 did not abrogate or delay this
      effect. Indeed, Ano-induced apoptosis was augmented by Cic. Cic 100 mumol.L-1
      itself stimulated 25% K562 cell apoptosis after 24-h culture. CONCLUSION: Ano
      induced apoptosis was independent of de novo protein synthesis.

PMID- 10072975
TI  - Influences of Kupffer cell stimulation and suppression on immunological liver
      injury in mice.
AB  - AIM: To study the possible involvement of Kupffer cells (KC) in immunological
      liver injury in mice. METHODS: Liver injury was induced by i.v. injection of
      Bacillus Calmette-Guerin (BCG) 5 x 10(7) viable bacilli followed by i.v.
      injection of lipopolysaccharides (LPS) 7.5 micrograms to each mouse. Indian ink
      and silica were i.v. injected to suppress KC and retinol was given po to
      stimulate KC in these mice. Plasma alanine aminotransferase (AlaAT), aspatate
      aminotransferase (AspAT), nitric oxide (NO), and liver tissue were examined.
      RESULTS: Injection of LPS following BCG injection resulted in a remarkable
      elevation of plasma NO, AlaAT, and AspAT levels, and severe liver damage. The
      damages were enhanced by the activation of KC with retinol and reduced by
      suppression of KC with silica and Indian ink. CONCLUSION: The degree of liver
      injury induced by BCG + LPS is closely correlated with the status of KC, and NO
      from KC plays an important role in the pathogenesis of the liver damage in mice.

PMID- 10072976
TI  - Effect of epidermal growth factor on cultured rat hepatocytes poisoned by CCl4.
AB  - AIM: To study the effects of epidermal growth factor (EGF) on CCl4-induced
      primary cultured hepatocytes injury. METHODS: Alanine amino-transferase (AlaAT)
      and aspartate aminotransferase (AspAT) activities and K+ concentractions were
      determined by the Auto-biochemistry Assay System. Malondialdehyde (MDA) was
      determined by thiobarbituric acid method. Radioactivity was determined by liquid
      scintillometry. Light microscopy and electron microscopy were used. RESULTS: EGF
      40 micrograms.L-1 decreased CCl4 (10 mmol.L-1)-induced damages of rat primary
      cultured hepatocytes by decreasing AlaAT and AspAT leakage and MDA production,
      and promoted RNA and DNA synthesis, with a high positive correlation between
      intracellular K+ leakage and DNA syntheses (r = 0.99, P < 0.01). Cytopathological
      study showed that EGF decreased damage of liver cells. CONCLUSION: EGF maintains
      the stability of cellular lipid membrane and promotes syntheses of RNA and DNA of
      hepatocytes, and intracellular K+ transference is a promotor of the message
      transmission of DNA synthesis.

PMID- 10072977
TI  - Effects of 10-hydroxy-2-decenoic acid on phagocytosis and cytokines production of
      peritoneal macrophages in vitro.
AB  - AIM: To study the effect of 10-hydroxy-2-decenoic acid (HDA) on the macrophages
      activity of rats in vitro. METHODS: To measure the effects of HDA on
      phagocytosis, the production of antitumor cytokines tumor necrosis factor (TNF)
      and interleukin-1 (IL-1) in vitro. RESULTS: HDA 50, 100 mg.L-1 promoted
      phagocytic activity from 0.353 +/- 0.017 to 0.39 +/- 0.04 and 0.382 +/- 0.017 A,
      increased TNF and IL-1 production from 0.23 +/- 0.07% to 0.43 +/- 0.04%, 0.47 +/-
      0.04% and from 2384 +/- 180 to 2943 +/- 295, 3825 +/- 450 dpm, respectively.
      CONCLUSION: The upregulating effects of HDA on phagocytosis of PMO and production
      of TNF, IL-1 contribute to the host antitumor and immunomodulating mechanism.

PMID- 10072978
TI  - Artificial reconstituted pulmonary surfactant in prevention and treatment of
      respiratory distress syndrome in neonates.
AB  - AIM: To test an artificial reconstituted pulmonary surfactant (APS) for
      prevention and treatment of respiratory distress syndrome (RDS). METHODS: A
      membrane-formed method combined with supersonic dispersing was used to prepare
      APS. A pulsating bubble surface tension measurement was established to compare
      surface properties of APS with natural pulmonary surfactant (NPS). A preliminary
      clinical trial was made for prevention and treatment of RDS. RESULTS: The APS
      reduced surface tension from 44.0 mN/m to < 1.0 mN/m in vitro. The changes of APS
      lipid contents were < 5% of labeled content at 37 degrees C. Clinical trial
      showed that the APS prevented RDS in 20/20 and cured RDS in 2/2 premature
      neonates. CONCLUSION: The APS had good surface properties similar to NPS.

PMID- 10072979
TI  - [Effects of 16 drugs on immunological liver injury induced by BCG +
      lipopolysaccharides in mice].
AB  - AIM: To evaluate anti-hepatitis drugs. METHODS: Mice were injected i.v. with
      viable BCG 5 x 10(7) (live) bacilli/mouse, after 10 d, i.v. lipopolysaccharides
      (LPS) 5-10 micrograms/mouse. Serum aminotransferase levels and liver tissue were
      examined 10 h after i.v. LPS. Sixteen drugs were evaluated in this model.
      RESULTS: The level of AlaAT and AspAT were increased markedly. Submassive
      necrosis and infiltrations of granulocytes and lymphocytes were seen, which were
      not recovered till 14 d after i.v. LPS. Administration of interferon alpha-2a,
      Ara-AMP, hepatocyte growth factor, biphenyl dimethyl dicarboxylate, bicyclol,
      prednisolone, and cyclophosphamide for 10 d prior to i.v. LPS suppressed the
      elevation of serum AlaAT and AspAT. CONCLUSION: The model of immunological liver
      injury reproduced by i.v. BCG + LPS in mice may be used for evaluating anti
      hepatitis drugs.

PMID- 10072980
TI  - [Hippocampal non-NMDA and GABA-A receptors in benzylpenicillin-induced epilepsy
      and electro-acupuncture antiepilepsy].
AB  - AIM: To study the effect of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and
      bicuculline (Bic) on benzyl-penicillin-induced-epilepsy (PIE) and
      electroacupuncture (EA) antiepilepsy in rats. METHODS: Epilepsy was elicited by
      intra-hippocampal microinjection of benzylpenicillin in rats. The analysis of
      electroencephalogram (EEG) and power spectrum was used to measure the extent of
      convulsion. RESULTS: EA or DNQX (1 microgram) showed partial inhibitory effect on
      PIE. EA + DNQX caused further inhibition of PIE, and Bic attenuated EA
      antiepileptic effect. CONCLUSION: Antagonization of GABA-A receptor attenuated EA
      antiepileptic effect, and EA acted synergistically with the antagonists of non-N
      methyl-D-aspartate (non-NMDA) receptors.

PMID- 10072981
TI  - Isolation and characterization of a new chromosome 8q24.1 band-specific
      microsatellite polymorphism.
AB  - A clone, containing a 24-dinucleotide (CA)-repeat sequence, was isolated from
      chromosome 8q24.1 band-specific pUC19 library. It was localized to target
      chromosome using human-rodent hybrid cell panel. Eleven alleles were estimated
      from 56 unrelated individuals and the heterozygosity reaches 0.835. Linkage
      analysis of 11 Chinese pedigrees showed significant evidence for linkage of this
      new marker to three dinucleotide repeat markers at 8q23-24.1 region, with the
      most likely position of the marker between D8S85 and D8S199.

PMID- 10072982
TI  - [Cross reaction of Trichinella spiralis larva antigens with sera of
      schistosomiasis japonica].
AB  - Cross reactions of T. spiralis muscular larva antigens (TsMLA) against several
      sera from patients with other parasitic diseases by ELIB (enzyme-linked
      immunoblotting technique) were studied. The proteins of 31-100 KDa were
      recognized by sera of two cases of acute schistosomiasis, while proteins of
      44/45, 51/53, 62/64 and 100 KDa were recognized by sera of 11 cases of chronic
      schistosomiasis. The proteins of 60 KDa showed varied cross reactions against
      sera of five kinds of patients with other parasitic diseases (filariasis,
      hookworm diseases, paragonimiasis, ascariasis and clonorchiasis). Only the
      proteins of 45 KDa were recognized by six of fifteen cases of normal human sera.
      All of > 29 KDa proteins were recognized by sera of rabbit infected by T.
      spiralis. It is suggested that there were many antigens in Trichinellen muscular
      larva which shared in common with several other parasites. The cross reactions of
      TsMLA against Schistosoma japonicum may be differentiated on the positive
      reaction bands of 44/45, 51/53, 62/64 and 100 KDa proteins which was specific to
      the chronic schistosomiasis using the TsMLA by means of ELIB.

PMID- 10072983
TI  - [Neoplasm-inhibiting effect and sensitivity-promoting effect of indomethacin in
      vitro].
AB  - OBJECTIVE: To explore an anti-tumor effect of indomethacin on human colon
      adenocarcinoma cell line HCT116, and its mechanism. METHODS: MTT, agarose gel
      electrophoresis, TdT and flow cytometry were used to study cell proliferation and
      apoptosis. RESULTS: Indomethacin significantly inhibited the proliferation of
      HCT116 cells and induced apoptosis with a "dose-time" dependent pattern. A
      synergic effect of inhibiting cancer cells proliferation was observed when
      combined with 5-Fu. CONCLUSION: Inhibition of proliferation and induction of
      apoptosis contribute to the mechanisms for anti-tumor activity of indomethacin.

PMID- 10072984
TI  - [Effect of EBV-LMP and EGF autocrine on proliferation of nasopharyngeal carcinoma
      cell line CNE and their relationship in action].
AB  - EBV-LMP gene transfection, radioimmuno-binding assay (RIA) and colorimetric cell
      viability assay (MTT) were used to investigate the effect and relationship of EBV
      LMP and EGF autocrine on the growth and proliferation of well differentiated
      nasopharyngeal carcinoma cell line (CNE1). Autocrine EGF was detected in the
      supernant of CNE1 cells and CNE1 cells could grow in serum-free medium,
      implicating that the cell proliferation-promoting effect of EGF autocrine was
      present in the CNE1 cell line. Nevertheless the positive signals of LMP gene
      polymerase chain reaction and LMP Mab immunohistochemical staining in pCMV alpha
      LMP DNA transfected cells, confirmed the successful transfection of LMP gene. EGF
      autocrine amount and the proliferation of CNE1 cells in serum-free medium were
      more obvious in post-transfected cells than those in untransfected cells. The
      present study represents the first report on promotion of EGF autocrine in EBV
      LMP-transfected cells, thus promoting cell proliferation.

PMID- 10072985
TI  - [Expression of CerbB-2 and EGFR mRNA in human nasopharyngeal carcinomas and
      pericarcinomatous tissues].
AB  - Using the digoxin labelled probes and DNA-RNA in-situ hybridization technique,
      the expression of C-erbB-2 and EGFR mRNA in routine paraffin sections of 30 human
      nasopharyngeal carcinomas (NPC), 20 pericarcinomatous tissues (PCT) and 16
      chronic inflammatory mucosae. The results showed the positive rates of C-erbB-2
      and EGFR mRNA expression were 86.7%, 83.3% respectively in NPC and 80.0%, 70.0%
      in PCT, while those in chronic inflammatory mucosae were no detected. Co
      expression of these two genes occurred in 83.3% of NPC and 70.0% of PCT. In the
      PCT, the positive rates of C-erbB-2 and EGFR mRNA in the atypic hyperplasia were
      higher than that in the simple hyperplasia, the amount of the positive cells of
      these two genes increased steadily in the mild, moderate and severe dysplasia and
      diffused from basal lamina of epithelium to the whole epithelium. The results
      suggest that the activation of C-erbB-2 and EGFR genes is an early event and play
      a synergic role in the carcinogenesis of NPC and examination of their expression
      is helpful in early diagnosis.

PMID- 10072986
TI  - [Gene frequency of HPA among Hunan population of Han nationality].
AB  - We used allele specific primer PCR (ASP-PCR) method to detect the genotype of
      five major HPA systems among Hunan population of Han nationality. The results
      showed: The gene frequency of PLA1 was 81.00% and 85.87% for Kob, 71.00% for
      Baka, 91.00% for Pena, 90.67% for Brb which provided the basis for further
      clinical application of HPA.

PMID- 10072987
TI  - [An investigation of precipitation of airborne fungi particles in the rooms of
      university library].
AB  - Precipitation of airborne fungi particles in the rooms of an University library
      and the influencing factors were studied in May 1994 with the fallen plate
      method. The total average precipitation of airborne fungi particles was 11.68 per
      dish in 5 minutes. The differences were significant from different room patterns,
      floors and times, so were the humidity assayed. The book-store rooms and reading
      rooms had an average precipitation of 15.01 and 8.35 per dish in 5 minutes
      respectively (P < 0.05), and humidity of 41.7 and 11.4 percent respectively (P <
      0.01). The influencing factors were: different floors and room patterns, the
      people's activity, the different time, humidity, ventilation and book pollution.

PMID- 10072988
TI  - [Influence of qi-gong on plasma TXB2 and 6-keto-PGF1 alpha in two TCM types of
      essential hypertension].
AB  - Forty-five patients of essential hypertension differentiated into two TCM types,
      i.e. Gan Yang Shang Kang Zheng (GYSK) and Yin Xu Yang Kang Zheng (YXYK) were
      randomly selected. Among them, the 31 patients received qi-gong therapy including
      12 GYSK cases (group b) and 19 YXYK cases (group c) and 14 patients (group d)
      received nifedipine therapy. It was found that the plasma 6-K-PGF1 alpha was
      increased and TXB2 as well as TXB2/6-K-PGF1 alpha ratio were decreased after the
      therapy (P < 0.05) in group b, c and d. No statistical significant difference was
      found between group b and group c (P > 0.05). The results suggest that qi-gong is
      regulatory on TXB2 and 6-K-PGF1 alpha in patients with essential hypertension and
      is identical in the two different TCM Zheng types.

PMID- 10072989
TI  - [Surgical handling of primary hepatic carcinoma with severe cirrhosis and portal
      hypertension].
AB  - Four hundred and ninety eight cases of primary hepatic carcinoma (PHC) were
      discovered complicating with cirrhosis in 608 PHC cases during 1974-1994. 63
      cases of them were with severe cirrhosis and portal hypertension (10.4%).
      Laparotomy indication was evaluated according to Child's grade and image data
      such as BUS and CT etc. Operative extension should be limited as segment or wedge
      hepatectomy or semi-hepatic artery chemo-embolization. Splenic artery ligation
      plus venous ligalion of cardiac region of stomach were applied to portal
      hypertension and hypersplenism. Frusemide, antacid and insulin were used in the
      perioperation period. Three-year survival rate was 57%. It is considered that
      splenic artery ligation instead of splenectomy is the first choice for preventing
      and treating hypersplenism and digestive tract bleeding in PHC with severe
      cirrhosis.

PMID- 10072990
TI  - [Electrocardiographic signs of atrial overload in hypertension].
AB  - The aim of the study was to investigate the incidence of the ECG signs of atrial
      overload in hypertensive patients (HT) and its relationship to the state of the
      illness and cardiac function. ECG, mechanocardiogram and impedance cardiogram
      were performed in eighty-two HT and found P > 0.10, P/P-R > 1.6, P-S4 < 140 ms
      were more common (50%-73.2%) than PEP/LVET (46.3%) and DATI (29.1%). P/P-R = 1.96
      +/- 0.588 in Stage 1 of HT, 2.204 +/- 0.678 in Stage 2 showed that P/P-R had a
      definite relationship to the stage of disease (P < 0.05). For those P-S4 were
      abnormal the PEP/LVET was increased and DATI decreased. All of these showed a
      simultaneity in ECG signs of atrial overload embodied the abnormal diastolic
      function of ventricle. In further analyses, P(ECG), A(ACG) and S4(PCG) may be
      changed but not keeping synchronous, so they can not be replaced with each other.

PMID- 10072991
TI  - [The serum insulin level in severe hepatitis patients].
AB  - Serum insulin (SI) levels were determined in 36 severe hepatitis patients by RIA.
      The average level of SI in chronic severe hepatitis (CSH) patients was 43.18 +/-
      27.12 mu.L-1, and subacute severe hepatitis (SSH) patients 28.91 +/- 12.77 mu.L
      1. Both were increased significantly as compared with normal controls (P < 0.01),
      and the level of SI in patients died from SSH and CSH was increased significantly
      than those alive (P < 0.05). The level of SI at the fastiguium stage of the
      disease was significantly higher as compared with that of the convalescence stage
      (P < 0.05). The results suggest that SI may aid to evaluate the severity of the
      illness and to estimate the outcome of the patients.

PMID- 10072992
TI  - [Fixation of nonunion of pediatric middle and distal shaft of the femur with
      semicircular dynamic locked intramedullary nail].
AB  - From Oct. 1994 to Dec. 1996, 15 nonunions of pediatric middle and distal shaft of
      the femur due to previous osteomyelitis and pathologic fracture and/or failed
      internal fixation were treated with semicircular dynamic locked intramedullary
      nail (SDLIN). SDLIN was composed of a lateral and a medial nail, both of them
      were inserted into the medullary canal 1.5 cm above the epiphyseal line, and the
      tails were connected together by a bolt. All the 15 cases used iliac bone
      autograft for the defect. Follow-uped for an average of 16.3 months, all of them
      were healed in an average of 4.8 months, and excellent and good results were
      obtained in 86.7%. The results suggest that the SDLIN is effective and convenient
      for the fixation of the refractory nonunion of pediatric middle and distal shaft
      of the Femur.

PMID- 10072993
TI  - [Nitric oxide, TNF-alpha and IL-8 in cerebrospinal fluids of tuberculous and
      cryptococcic meningitis].
AB  - The contents of NO, TNF-alpha and IL-8 in the cerebrospinal fluids (CSF) of
      patients with tuberculous and cryptococcic meningitis were detected. The results
      showed that the concentration of NO2-/NO3- and the levels of TNF-alpha and IL-8
      in CSF of the two kinds of meningitis were higher than those of normal CSF, and
      the concentration of NO2-/NO3- correlated positively to the content of TNF-alpha.
      The results indicate that the over production of NO, TNF-alpha and IL-8 in CSF
      may involve in the tissue inflammation and damage of central nerve system
      infection.

PMID- 10072994
TI  - [Clinical application of highly selected embolotherapy via external carotid
      artery in craniofacial diseases].
AB  - Forty-three cases of hypervascularized tumors and vascular lesions supplied by
      external carotid artery were treated by endovascular embolization. The results
      showed that hypervascularized tumor's bleeding markedly reduced and its volume
      diminished during operation; vascular lesions were cured or improved after
      embolization. The choice of embolic materials and technical essentials were
      discussed.

PMID- 10072995
TI  - [99mTc-MIBI myocardial perfusion imaging in patients with diabetes].
AB  - Seventy-four patients with diabetes were taken on both stress and rest 99m-Tc
      MIBI SPECT imaging: 44 patients (59.5%) were found having myocardial ischemic
      disorders, including 28 cases of myocardial ischemia, 7 cases of myocardial
      infarction and 9 cases of both conditions. 113 segments were involved and 46%
      were located in the posterior and inferior walls, indicating that the right
      coronary artery is most susceptive to ischemia. Diabetic patients complicated
      hypertension and/or hyperlipidemia were at higher risk of either early occurrence
      of coronary disease. 99mTc-MIBI SPECT imaging is helpful in early diagnosis and
      therefore is significant in directing.

PMID- 10072996
TI  - [Respiratory monitoring and high frequence jet ventilation (HFJV) in the
      treatment of severe chest injuries].
AB  - Twenty-eight patients with severe chest injuries were classified into 3 groups:
      fractures of rib, hemopneumothorax and lung injured. Their respiratory rate (RR),
      SpO2 and blood gas were analysed. The results showed that SpO2 and PaO2 in lung
      injured group were the lowest and RR was the highest in the 3 groups. After HFJV,
      there was a significant rise in PaO2 and SpO2 (P < 0.05) and a gradual recovery
      of respiratory and pulse rates in lung-injured group. The results suggest that
      respiratory monitoring is important for patients with chest injuries and HFJV may
      be used as an effective ventilation method for treating patients with severe
      chest injuries.

PMID- 10072997
TI  - [Plasma and skin tissue endothelin in patients with psoriasis vulgaris].
AB  - The levels of plasma endothelin in 46 patients with psoriasis vulgaris and the
      levels of endothelin in skin tissue of 25 cases were determined by RIA. The
      results showed that: (1) The plasma levels of endothelin in patients with
      psoriasis vulgaris was significantly increased compared with that of the controls
      (P < 0.01), so was the active stage group compared with the stable stage group (P
      < 0.01); (2) The level of endothelin in skin lesions of patients was
      significantly higher than that of the uninvolved skin. These findings suggest
      that endothelin might play a role in the pathogenesis of psoriasis vulgaris.

PMID- 10072998
TI  - [Clinical evaluation on parenteral nutrition in neonatal disease].
AB  - Thirty cases of neonatal disease were treated with parenteral nutrition (PN) as
      an adjuvant treatment and compared with the control group (n = 30). The body
      weight and plasma albumin increased remarkably in the PN group (P < 0.01, P <
      0.05). No significant metabolic complication was occurred (P > 0.05). PN proved
      to be a safe and effective approach for neonatal patients, in which nutritional
      admixture components were adjusted day by day according to gestational age, body
      weight, disease course and monitor indexes to match the actual gastric intestinal
      tract function.

PMID- 10072999
TI  - [Rapid bioluminescence method for pathogen detection of nephropyelitis patient].
AB  - ATP is a kind of necessary metabolites in the living cells. We detected ATP
      contents in 222 bacteriuria or the urine germ by bioluminescence method. The
      results showed that the patient had been infected when the mean value was > 130.9
      +/- 11.38 and had not when the mean value was < 32.9 +/- 2.26. The results were
      the same with the Gram Stain, L-form bacteriuria culture and the common
      bacteriuria culture. The mean values of positive specimens are higher than that
      of the negative specimens by the bioluminescence. Thus, it is indicated that the
      bioluminescence method has high sensitivity. This method can be used to detect L
      form bacteriuria in the urine germ quickly and is important for early diagnosis
      by the doctors.

PMID- 10073000
TI  - [T-lymphocyte subgroup and the nature killer cell activity in cardiovascular
      diseases].

PMID- 10073001
TI  - [Relation between general symptoms and psychosomatic symptoms in patients with
      chronic prostatitis].

PMID- 10073002
TI  - [Gas-chromatographic determination of 3-methoxy-4-hydroxy-mandelic acid in
      urine].

PMID- 10073003
TI  - [Insulin autoantibodies (IAA) in sera of individuals with negative values in IAA
      radioimmunoassay].
AB  - Insulin autoantibidy(IAA) is one of the most important markers for detection of
      population at risk to develop into Type I diabetes. In screening the subjects and
      following up their conditions, the authors re-examined some sera with IAA
      radioimmnoassasy by using different concentrations of unlabeled insulin. The
      results of these subjects were compared with those of normal controls and IAA
      positive diabetics. It was confirmed that there was actually a large amount of
      IAA in the sera of individuals with negative values in standard IAA
      radioimmunoassay. Only in this group, the levels of IAA varied with increased
      amount of unlabeled insulin (P < 0.01). Should similar events be confronted, it
      is advisable to increase the amount of unlabeled insulin in IAA radioimmunoassay
      on purpose to avoid missed diagnosis.

PMID- 10073004
TI  - [Expression of epidermal growth factor and its receptor in human primary
      hepatocellular carcinoma].

PMID- 10073005
TI  - [Chinese herbal drugs: sheng-bai-kuai in the treatment of leukopenia caused by
      chemotherapy].

PMID- 10073006
TI  - [Sea-blue histocytosis--a case report].

PMID- 10073007
TI  - [The significance of plasma D-dimer contents in patients with coronary heart
      disease].

PMID- 10073008
TI  - [Clinical uses of plasma exchange therapy in some diseases].

PMID- 10073009
TI  - [An improvement of the pliers used for pig jawbone fixation in operation].

PMID- 10073010
TI  - [Granulomatous trichophytosis rubrum. Report of 2 cases].

PMID- 10073011
TI  - [Carotenemia. Report of 11 cases].

PMID- 10073012
TI  - [Identification of antigens in circulating immune complexes of schistosomiasis
      japonica].
AB  - In order to identify antigens in circulating immune complexes (CIC) of
      Schistosoma japonicum, the antiserum against CIC was first successfully prepared
      by immunization of New Zealand rabbit with CIC isolated from schistosome-infected
      rabbit sera. The antigens in CIC were identified and analyzed by EITB (enzyme
      linked immunoelectro-transfer blot) techniques, using the prepared antiserum
      against CIC, adult worm antigens (AWA), soluble egg antigens (SEA) and adult
      excretory antigens (ESA). The results showed that the antiserum against CIC had
      recognized the AWA bands of 155, 90, 70, 31/32, 20.5, 14 and 8 KD; the SEA bands
      of 90, 66, 46, 34.5 and 27 KD and the ESA bands of 155, 92, 87.5, 70, 60, 57.5,
      50, 46, 36, 31/32, 24, 18.5, 12 and 8 KD. These findings indicate that the
      antigens in CIC were derived from both schistosome adult worms and eggs. In
      addition, the localization of the antiserum against CIC targeted antigens in
      adult worms was also carried out by IFAT (indirect flourescent antibody test). It
      is suggested that the antigens in CIC were presented mainly in the tegument and
      the gut of the parasite.

PMID- 10073013
TI  - [Detection of different class (subclass) antibodies in sera of patients with
      schistosomiasis japonica for diagnosis and efficiency evaluation].
AB  - The subclass antibodies against IgG1, IgG3 and IgG4 in sera of the patients with
      chronic Schistosomiasis japonica were detected before treatment, and after
      treatment--6 and 12 months respectively, using Biotin-Avidin-ELISA (BA-ELISA)
      established by purified 31/32 KD antigen from the adult worms. At the same time
      IgG1 and IgM were examined by the standard ELISA. False positive reaction with
      normal control and cross reaction with other parasitic diseases have not been
      observed. The IgG1 and IgG3 subclasses showed high sensitivity and specificity
      and reduced quickly 6 months after treatment. These results indicate that the
      level of specific IgG1 and IgG4 to the 31/32 KD adult worm protein has high value
      for diagnosis of Schistosomiasis japonica and evaluation of the curative
      efficiency of the disease.

PMID- 10073014
TI  - [Induction of apoptosis by tea polyphenols in MGC cells].
AB  - In order to search for tumor cells apoptosis inducer, the apoptosis effects and
      mechanism of tea polyphenols were studied. Tea polyphenols is an active compounds
      purified from tea. The apoptosis effects of tea polyphenols were observed on the
      human gastric carcinoma cells (MGC) by MTT reduction test, DNA agarose gel
      electrophoresis and transmission electron microscopy (TEM) technique. Having been
      treated by tea polyphenols in 125 micrograms.ml-1 for 24 h, DNA extracted from
      MGC cells showed a typical internuclesosomal DNA degradation, i.e., DNA ladder
      and apoptotic vehicles were observed under TEM. The effects of tea polyphenols
      were shown to parallel with its cytotoxic activity in MGC cells. These results
      suggest that the mechanism of antitumor action of tea polyphenols is related to
      its apoptosis inducing activity.

PMID- 10073015
TI  - [A non-invasive method for detecting endothelium-dependent dilation].
AB  - Using high resolution ultrasound, we measured the diameter of brachial arteries
      at rest, during reactive hyperemia and after glyceryl trinitrate (GTN) taking in
      22 healthy persons. The results showed that brachial artery dilation was present
      both in reactive hyperemia and response to GTN. The mean flow-mediated dilation
      was 13.8 +/- 3.9% increment. The mean increment of dilation in response to GTN
      was 24.9 +/- 9.7%. The diameters of brachial arteries during reactive hyperemia
      and after sublingual GTN had significant difference compared with that in
      baseline (P < 0.01). It indicates that increased flow may mediate endothelium
      dependent vessel dilatation and GTN cause endothelium-independent vessel
      dilatation in normal subjects. This paper presents a new non-invasive method of
      detecting endothelium-dependent dilation, which is proved to be simple, secure
      and practical.

PMID- 10073016
TI  - [The comparison of sensitivity of BGM cells, HeLa cells, HEL cells and A 549
      cells to herpes simplex virus-1].
AB  - This study was undertaken to compare sensitivity of buffulo green monkey (BGM)
      cells, Hela cells, human embryo lung (HEL) cells and A549 cells to herpes simplex
      virus-1. The plague forming unit (PFU) technique was used to measure the four
      cell lines simultaneously. The results showed that BGM cells were superior to the
      Hela cells, HEL cells, A549 cells in terms of both sensitivity and rapidity of
      appearance of cytopathic effect (CPE). It indicates that BGM cells constitute a
      new, sensitive and valuable cell line used for the detection of HSV-1 in cell
      culture.

PMID- 10073017
TI  - [Protective effects of nimodipine on brain edema induced by pertussis bacilli in
      rats].
AB  - The changes of brain water content and Evan blue(EB) were investigated on the
      model of infection brain edema induced by Pertussis Bacilli(PB) in 72 rats.
      Nimodipine was admenistred to show its effect on the PB induced brain edema. The
      experiment results showed that the water content and EB content in the PB group
      were significantly increased than those normal group and normal saline group at
      30 min, 4 hours and 24 hours after the injection of PB (P < 0.05). Nimodipine
      could significantly reduce brain water content and EB content, so that brain
      edema was attenuated. It indicates that nimodipine showed advantage to treatment
      of PB brain edema.

PMID- 10073018
TI  - [Experimental studies of jiantang oral solution on reducing glycemia].
AB  - Mice or rats were pretreated P. O. with 8.0 gg.kg-1, 15.0 g.kg-1 and 30.03 g.kg-1
      of Jiangtang Oral Solution once daily for 10 days respectively. The results
      showed that Jiangtang Oral Solution did not affect the glycemia and lipid in
      normal mice and rats, but significantly lowered the blood sugar in hyperglycemic
      mice and rats induced by alloxan, adrenalin, and streptozotocin. Meanwhile,
      Jiangtang Oral Solution significantly lowered blood lipid in mice and rats
      induced by yolk and high cholesterol foods. This study provides a reliable
      pharmacologic base for the clincal use of Jiangtang Oral Solution.

PMID- 10073019
TI  - [Alterations of p53 gene in human ovarian tumor].
AB  - Using polymerase chain reaction--single strand conformational polymorphisms and
      EB staining techniques, 43 ovarian tumors were detected in the exons 5-8 of p53
      gene. The results showed that alterations of p53 gene were 0/10(0%) in benign,
      1/3(33.3%) in borderline, 14/30 (46.6%) in malignant ovarian neoplasms. In our
      series, the alterations of p53 gene were present in bordline tumor and stage I to
      stage i.v. cancer. The results suggest that the alterations of p53 gene are
      closely correlated with initiation of ovarian cancer and may be involved in the
      pathogenesis of ovarian carcinoma. It may be an early event and play an improtant
      role in the progression of human ovarian carcinoma.

PMID- 10073020
TI  - [Research thought and methods in studying laboratory diagnostic parameters of
      liver syndromes in traditional Chinese medicine].

PMID- 10073021
TI  - [The prevalence of hypertension, diabetes mellitus and hyperlipemia among 1369
      subjects for physical examination in Changsha].
AB  - A survey of the prevalence of hypertension (HT) and diabetes mellitus (DM) and
      hyperlipemia (HL) was conducted among 1369 subjects for health check in Changsha.
      The results showed that the prevalence of HT and DM and impaired glucose
      tolerance (IGT) and HL were 17.2% and 4.6% and 5.9% and 27.4%, respectively. The
      prevalence of HT and DM and IGT increased with age. The higher the body mass
      index was, the higher the prevalence of HT and DM and HL was. These findings
      indicate that the aging and over weight are important risk factors to the
      prevalence of HT, DM and HL.

PMID- 10073022
TI  - [Preliminary study on pathophysiological basis of liver-blood deficiency
      syndrome].
AB  - By ways of HPLC and RIA, multiple laboratory parameters were determined
      simultaneously in 84 patients of iron--deficiency anemia (IDA) or chronic
      aplastic anemia (CAA) with Liver-Blood Deficiency Syndrome (LBDS) diagnosed by
      differentiation of TCM. The results showed that LBDS had some pathophysiological
      characteristics such as decreased function of sympathicus and adrenal medulla
      axis, increasing of L-EK, lower energy metabolism of erythrocyte, lower rate of
      body metabolism, sodium and water imbalance, and abnormalities in hemorrheology
      and erythrocyte deformability. It is suggested that the patients with LBDS are in
      a state of protective compensation in blood volume regulation.

PMID- 10073023
TI  - [Changes and evaluation of indexes on treating ganyanghuafengzheng with cerebral
      infarction by tianlongxifeng granulae].
AB  - We used TIANLONGXIFENG granulae to treat the patients with GANYANGHUAFENGZHENG of
      cerebral infarction, and mobilely observed the contents of plasma norepinephrine,
      epinephrine, cortisol, thromboxane B2 and serum triiodothyroidoglobulin. The
      results showed that with the improvement of curative effect and the decrease of
      symptom scores, the contents of parameters mentioned above changed accordingly.
      It is suggested that these parameters may have value for diagnosis.

PMID- 10073024
TI  - [Study of the mechanism of regression of left ventricular hypertrophy in
      hypertension treated with slow-release verapamil].
AB  - Thirty-three hypertensive patients with left ventricular hypertrophy were treated
      with slow-release verapamil for 1 year. The left ventricula mass index (LVMI) and
      the concentration of intracellular calcium ion ([Ca2+]i) of lymphocytes were
      studied respectively at the beginning, the third, the sixth and the twelveth
      month of treatment. The results revealed that: 1 the LVMI was positively
      correlated with [Ca2+]i and mean arterial pressure (MAP); 2 the LVMI, [Ca2+]i and
      MAP were significantly decreased, after treatment; 3 the degree of reduction of
      LVMI (delta LVMI) was positively correlated with the degree of lowering of
      [Ca2+]i (delta [Ca2+]i) and MAP (delta MAP); 4 the LVMI and [Ca2+]i showed no
      significant change at the third month but significant decrease at the sixth and
      twelveth month of treatment. It suggests that besides the decrease of MAP the
      decrease of [Ca2+]i is a significant factor for mechanism of regression of LVH.

PMID- 10073025
TI  - [Early revascularization by percutaneous transluminal coronary angioplasty in
      acute myocardial infarction].
AB  - Twelve patients with acute myocardial infarction (AMI) underwent percutaneous
      transluminal coronary angioplasty (PTCA). The reperfusion blood flow of the
      infarct-related arteries (IRA) in eleven patients was TIMI Grade 3 with residual
      stenosis of 15.5 +/- 8.8%. Vascular endothelial dissection complicated by
      angioplasty was observed in one case and the patient died after emergency
      coronary artery bypass graft. It is suggested that early primary PTCA in AMI may
      create stable and effective revascularization which will favor reducing infarct
      size, improving myocardial pump function, and lowering restenosis and mortality
      rate.

PMID- 10073026
TI  - [The changes of plasma endothelin concentration and its clinical significance in
      pulmonary hypertension associated with congenital heart defects].
AB  - Plasma endothelin (ET) concentration was measured by means of radioimmunoassay in
      38 patients with congeital heart defects among whom 15 patients with pulmonary
      hypertension (PH) and 23 patients without pulmonary hypertension (non-PH). Blood
      samples were obtained separately from the femoral vein, right atrium, right
      ventricle, main pulmonary artery and the femoral artery during catherization.
      Plasma ET concentration in the PH group was significantly higher than that in the
      non-PH group at all four sampling sites. In the PH group plasma ET concentration
      in the pulmonary artery showed higher than that of the right ventricle and the
      femoral artery, which was significantly in positive correlation with pulmonary
      artery pressure. It is considered that the elevation of ET plays an important
      physiological role in the formation of pulmonary hypertension.

PMID- 10073027
TI  - [Influence of cryotherapy on the concentration of malondialdehyde in rats serum].
AB  - Malondialdehyde (MDA) consistency in rats serum was measured when performing
      cryotherapy by means of fluorescence method. The rsult showed MDA consistency in
      rats serum increased after cryotherapy, and the highest MDA consistency appeared
      respectively in the 2nd week, 4th week and 7th week (P < 0.01). The variation of
      MDA consistency in mice serum is identical to that when carrying out cryotherapy,
      which demonstrates that lipid peroxidation involves the whole course of injury
      and recovery of cryotherapy.

PMID- 10073028
TI  - [Ventriculo-peritoneal shunts for thirty-two patients with traumatic
      hydrocephalus].
AB  - Thirty-two patients with traumatic hydrocephalus were treated by ventriculo
      peritoneal shunts. Twenty-two patients were improved (70%). Among them, seventeen
      patients showed satisfactory results (53%): ventriculo-peritoneal shunts have
      good effects and few complications; this method is easy to manipulate for
      traumatic hydrocephalus. We discussed the important points in operations.

PMID- 10073029
TI  - [Clinical obeservation of improved passing peritoneum extraperitoneal cesarean
      sectron].
AB  - One hundred and fifty puerperas who had indications for cesarean section and
      factors associated with intrauterine infection were random divided into three
      groups and adopted three different operative proccdures which were improved
      passing peritoneum extraperitoneal, extraperitoneal and low segement cesarean
      section respectively. Three were 50 puerperas in each group, seven paremeters
      were observed during and after operation. The results showed that the mean times
      of three groups from cutting skin to fetal head delivered were 19.5, 22.6 and
      19.9 minutes respectively (P < 0.05), the mean operative times were 58.04, 68.2
      and 72.0 minutes in proper urder (P < 0.01). Gastrointestinal function recovery
      mean times were 26.6, 26.0 and 47.9 hours (P < 0.01) in sequence. Postoperative
      morhidity rates were 10%, 12% and 24% (P < 0.01) in order. Postoperative
      comlicatins were 0%, 26% and 6% (P < 0.01). There were no significant difference
      both in newborn one minute Apgar grading and blood loss volume during the
      operation in three groups. Improved passing peritoneun extraperitoneal cesarean
      section is a simple, convenient, safe and practical oprative method. It is
      especially applied to those cases who have a bad form of uterine hypomere and
      factors of intrauterine infection.

PMID- 10073030
TI  - [Significance and changes of plasma endothelin in patients undergone upper
      abdominal surgery].
AB  - We observed the changes of plasma endothelin, hemodynamic and electrocardiogram
      in twelve patients undergone upper abdominal surgery under epidural anesthesia.
      The results showed that mean artery pressure, heart rate, cardiac output, cardiac
      index, systemic vascular resistance, maximum left atrial pressure, maximum
      ascendant speed of artery systolic pressure and mean ascendant speed of artery
      systolic pressure were all significantly lower during intraab-dominal exploration
      than that of preanesthesia (P < 0.01). Mean artery pressure and systemic vascualr
      resistance kept low levels to the end of operation. Plasma endothelin was
      significantly higher at 1 hour after skin resection than that of preanesthesia (P
      < 0.01) and was apparently negative related with cardiac output(CO) and cardiac
      index(CI) during exploration(CO r = -0.9221; CI r = -0.8768), two patients' with
      myocardial ischemia were specially higher. We conclude that plasma endothelin is
      closely related with cardiac function and myocardial ischemia during operation.

PMID- 10073031
TI  - [Clinical study of bioactive glass ceramics as orbital implants].
AB  - One hundred and two patients received a bioactive glass ceramics as an orbital
      implant of 98 cases 96.1% were successful after operation. Of 4 cases that
      underwent operation, conjunctiva was torn partly when stitches were taken out of
      the wound. One out of four had to remove the orbital implant. After a follow-up
      of 6 months to 2 years, there were no complications. All patients were satisfied
      with their cosmetic appearance and motility although drilling of the motility
      hole as a secondary procedure was not peformed.

PMID- 10073032
TI  - [One-year-result of excimer laser for photorefractive keratectomy in very high
      myopia].
AB  - We corrected 53 cases (84 eyes) of very high myopia using photorefractive
      keratectomy (PRK) with VISX 20/20 excimer laser, and followed up the cases more
      than one year. The rates of visual acuity more than or equal to 0.5 or 1.0 were
      81.0% and 23.9%, 75.0% eyes were within +/- 2.00 diopter of the desired
      emmetropia. Grade 2 or more severe corneal haze were presented in 13.1% eyes. PRK
      with VISX 20/20 excimer laser may be an effective method to correct very high
      myopia from -10.00 to -16.00 diopters.

PMID- 10073033
TI  - [Analysis of 24-hour ambulatory EEG monitoring in 315 children with paroxysmal
      diseases].
AB  - The 24-hour ambulatory electroencephalography monitoring (AEEG) of 315 children
      with various paroxysmal diseases were monitored. Among them 224 cases (71.11%)
      were lightly abnormal including 142 cases (45.08%) recorded as epilepsy burst;
      the absence seizures and convulsions were the highest positive rates in these
      patients who have been recorded epilepsy burst. We found that AEEG was more
      accurate to get abnormal burst wave or epilepsy burst wave than EEG. These data
      may indicate that AEEG is more accurate in children with paroxysmal diseases.

PMID- 10073034
TI  - [CT for diagnosis of parathyroid adenoma].
AB  - We analyzed Ct findings of 10 cases with parathyroid adenoma which had been
      verified by surgery and pathologic section. The correct localization of 9
      adenomas was made by CT preoperatively. The method of CT scanning of parathyroid
      adenoma were elucidated. The results showed that most adenomas were located in
      the groove between trachea and esophagus. The contour of tumors was oval, the
      edge was smooth and regular. Enhancement CT images were helpful for
      differentiating the tumor from blood vessel. It is indicated that CT scanning is
      a good method for localizing the parathyroid adenoma.

PMID- 10073035
TI  - [The significance of midline structure shifting in the patients of cerebral
      hemorrhage in basal ganglia by computerized tomography].
AB  - Thirty-six patients of cerebral hemorrhage in basal ganglia were studied between
      medline structure shifting on CT scan and assessment of clinic neurological
      function, defect (AND). The differences were significant between the following
      two groups: including in parameter A (the distance from center of hematoma to
      normal midline), 26.01 +/- 6.06 mm in survivor group, 21.53 +/- 5.03 mm in death
      group; in parameter B (the distance from the farthest point in shifted midline to
      the normal midline), 3.84 +/- 2.66 mm in survivor group, 10.32 +/- 4.24 mm in
      death group; in parameter C (ratio of the partial length of shifted midline to
      all length of the normal midline), 0.347 +/- 0.136 in survivor group; 0.582 +/-
      0.082 in death group. Having analized these parameters, the authors found that
      the mortality rates were 0 and 100% if B was < or = 4.0 mm and > 10.0 mm
      respectively and the mortality rates were 0 and 90% if C was < or = 0.30 and >
      0.50. The authors also found that there was closed correlation between the
      parameters B or C described midline shifting and AND.

PMID- 10073036
TI  - [Determination of inorganic phosphate in serum by double reagents with Hitachi
      7170 A analyzer].
AB  - We propose a method for determination of inorganic phosphate in serum using
      double reagents with Hitachi 7170 A analyzer. The standard curve for phosphate
      was linear from 1.0-5.0 mmol.L-1. Both coefficient of accuracy and precision were
      above 95%. The recovery rate ranged from 98.2%-99.5%. Jaundice Sample and
      lipohemia serum were found to be interference--free. This method can eliminate
      paraprotein interference, it was an ideal method for determination of inorganic
      phosphate in serum.

PMID- 10073037
TI  - [Study of detecting p53 gene of laryngeal carcinoma on paraffin-embedded tissue
      sections by in situ polymerase chain reaction].
AB  - In order to investigate alterations of p53 gene in laryngeal carcinoma, five
      cases of paraffin-embedded tissue were detected by in situ polymerase chain
      reaction (PCR). The results showed that p53 gene was presented in more than 90%
      of cancer cells in all cases with exon 5 specific primers, which signal copy
      numbers were 2.24 +/- 0.23. It suggests that in situ PCR and paraffin-embedded
      tissue are able to be used in the single copy gene research. The improvement and
      application of the technique were discussed.

PMID- 10073038
TI  - [Predication of hemodynamic changes of rheumatic heart disease with P wave of
      electrocardiogram].

PMID- 10073039
TI  - [Oxyhemoglobin saturation: correlation between venae cavae, right atrium, right
      ventricle and pulmonary artery].

PMID- 10073040
TI  - [Photorefractive keratectomy to correct myopic astigmatism].
AB  - The VISX 20/20 excimer laser was used to treat 260 eyes with myopia and myopic
      astigmatism of 166 patients. All patients were followed up for one year. The
      diopter of preoperative astigmatism was from -0.25-(- 4.00 D (-1.00 +/- 0.62 D).
      The diopter was lowered to -0.07 +/- 0.40 D at 6 months postoperatively (P <
      0.05) and -0.06 +/- 0.39 D at 12 months postoperatively (P < 0.01).
      Photorefractive keratectomy (PRK) is effective and safe for myopic astigmatism.

PMID- 10073041
TI  - [Clinical analysis of bronchial tuberculosis].

PMID- 10073042
TI  - [Determination of template bleeding time in patients with chronic pulmonary heart
      disease].

PMID- 10073043
TI  - [A strain of Nocardia asteroides isolated from a patient with acute leukemia].

PMID- 10073044
TI  - [Polyradicular cysts. A case report].

PMID- 10073045
TI  - [Drug industry responsibility in the field of research and development].

PMID- 10073046
TI  - [Responsibility of the pharmaceutical industry in health safety].
AB  - Under this title will be recalled the responsibilities exerted by the
      Pharmaceutical Industry in two different fields: in the field of drug production,
      which has to meet the most rigorous constraints in matter of quality (Good
      Manufacturing Practices, quality assurance...) under supervision of the
      pharmaceutical structure; in the field of drug use: after the initial evaluation
      of the benefit/risk ratio, on which in based the drug registration, it is the
      responsibility of the Industry to contribute constantly to the good use of
      medicines and to its optimization (information of health professionals, patient
      information, pharmacovigilance, and if necessary sanitary safety measures...).

PMID- 10073047
TI  - [Professional profile and responsibility of the qualified person within the
      European Union].
AB  - The European Community has established a fundamental condition for opening a
      pharmaceutical laboratory, i.e. the designation of a qualified person having the
      professional profile detailed in the European Community Directive and who is
      responsible for implementing specific obligations. It is the final responsibility
      of this qualified person to release medicine on the market. Do to the importance
      of this person, we have analyzed his/her functions, obligations and
      responsibilities. The training required to fulfil the functions of a qualified
      person is presented. The profiles of qualified persons in the most representative
      European countries are discussed to demonstrate analogies and differences in
      national legislations and their adaptation to European Community regulations.

PMID- 10073048
TI  - [Xenogenic cell therapy in man].

PMID- 10073049
TI  - [Action of hydrostatic pressure on proteins: emergence of high pressure
      biotechnology, potential pharmaceutical and medical applications].
AB  - High pressure engineering of proteins is an emerging biotechnology. The role of
      pressure in the control of protein stability and reactivity is reviewed. It is
      shown that a better understanding of the behavior of proteins under extreme
      pressure and temperature conditions may help to improve biochemical processes
      under non conventional medial/conditions for enzyme-catalyzed production of fine
      chemicals and the use of modified proteins of medical or pharmaceutical interest.
      Moreover, high pressure can be used instead of heart or chemicals for
      sterilization.

PMID- 10073050
TI  - [Genetics and therapeutic intervention].
AB  - Elucidating the molecular mechanisms involved in metabolic diseases can, in many
      cases, characterize individual susceptibility resulting from mutations altering
      genetic inheritance. Better knowledge of this genetic component emphasizes the
      importance of revising disease classifications and diagnostic procedures which
      are currently based on phenotypic examination and may result in heterogeneous
      groupings of patients with different etiologies. By taking into account
      interindividual variability of therapeutic response, a new field of pharmacology,
      called Pharmacogenetics, may help evaluate and optimize therapeutic procedures in
      more homogeneous groups of patients.

PMID- 10073051
TI  - [Leukodepletion of labile blood products].
AB  - On the first of April 1998, French authorities decided on the systematic
      leukodepletion of two blood products: Red blood cell concentrates and platelet
      concentrates coming from homologous donors. This measure is based on the
      following principle arguments: Purification of the therapeutic product, as white
      cells are just passenger cells. White cells interfere with the red cells and the
      platelets during storage, deteriorating the overall quality of the blood product.
      There are multiple effects on the recipient of allogeneic leucocytes: CMH II
      structures stimulation of the host immune system; graft versus host reaction;
      cytokines secretion and mediators release; class I anti-HLA allo-immunisation; in
      general, immunomodulation (immunosuppression); intraleukocyte infectious agent
      transmission. Several techniques make leukodepletion in blood products possible:
      1. For the red cells, just one technique is basically used today: filtration
      either when the red cell concentrate is being prepared (filtering the whole
      blood), or after having obtained the concentrate, filtering that. The filters
      used today are from a third generation and their efficiency is above 99.9%. The
      final product contains thus less than 1.10(6) per unit, whereas the initial
      product contained 1.10(9) per cent. 2. For the platelets, apheresis technology
      makes it possible to obtain platelet concentrates directly leucoreduced
      (1.10(5)). However, there are still two questions: is this process also useful
      for plasma? and what about for autologous blood products?

PMID- 10073052
TI  - [Immunoblotting for the serodiagnosis of syphilis. A candidate to replace the
      Nelson-Mayer test].
AB  - The lipid antigens used in the Bordet-Wassermann and prepared by Landsteiner and
      Marie for syphilis tests from 1909 to 1949 were non specific but have certain
      common features with the spirochete body. For more than forty years the Bordet
      Wassermann reaction, associated with flocculation (Kahn) or agglutination (Kline
      VDRL) was used to detect cases of tremonematosis despite frequent false positives
      reactions due to other infections. In 1949, the Nelson and Mayer test was
      introduced. This test was based on a rigorously specific reaction based on an
      antigen of live virulent Treponema pallidum. Culture being impossible, the strain
      had to be, and still is, maintained by weekly passage on rabbit testicles. These
      manipulations are very dangerous and the technique is difficult, being performed
      only in specialized laboratories. This test however made it possible to identify
      the specificity of lipid tests and led to the development of specific
      immunofluorescent reactions (FTA) in 1959 and of hemagglutination test (TPHA) in
      1969. In 1980, we introduced a simple treponemic reaction (FTA or TPHA)
      associated with a lipid reaction (VDRL) for screening. The specificity of these
      tests is not however perfect and the Nelson test remains useful as a highly
      specific reaction. A simple test with comparable specificity was long awaited and
      is now available with immunoblotting as for HIV, boreliosis and pertussis, etc.
      We propose this new reaction to replace the Nelson test because it is specific,
      is sensitive early, distinguishes between IgG and IgM and is not dangerous to
      manipulate. We have tested it in over one hundred selected sera of CSF from
      subjects with recent, former or nervous syphilis as well as cases susceptible of
      producing false positive reactions and have concluded that immunoblotting is
      highly specific and sensitive. We recommend official approval of this test to
      replace the Nelson test.

PMID- 10073053
TI  - [Proposal for revision of the French bioethics law of July 29, 1994].
AB  - The president of the joint-academy working group (National Academy of Medicine
      and the National Academy of Pharmacy) will present the group's proposals for a
      revision of the 1994 French bioethics laws to the Parliamentary Office for the
      evaluation of scientific and technological choices in view of a new examination
      of the laws by the Parliament in 1999.

PMID- 10073054
TI  - MMR vaccine coverage falls in the United Kingdom.

PMID- 10073055
TI  - Cumulative reports of HIV infections in the UK exceed 37,000.

PMID- 10073056
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 10073057
TI  - Case reports in autism: issues in diagnosis and treatment.
AB  - Autism is a relatively common developmental disorder characterized by pervasive
      impairments in communication and social interaction as well as restricted
      interests and repetitive behaviors. Two case reports are presented to illustrate
      important aspects of diagnosis and treatment. Early clinical diagnosis is
      essential so that appropriate intervention can be implemented. A
      multidisciplinary approach to treatment is recommended due to the impact of
      autism on many aspects of behavior and development.

PMID- 10073059
TI  - The history of operative gynecologic laparoscopy in Kentucky.

PMID- 10073058
TI  - Acute promyelocytic leukemia. New methods in diagnosis and treatment.
AB  - Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid
      leukemia characterized by hypergranular leukemic cells, bleeding diathesis and
      t(15; 17) translocation. The t(15; 17) translocation leads to the production of
      the PML-RAR alpha fusion protein which plays a vital role in the pathogenesis of
      APL by arresting normal differentiation of myeloid precursors. However, in the
      presence of high concentrations of all-trans-retinoic acid (ATRA), the PML-RAR
      alpha fusion protein serves to stimulate cell differentiation. The diagnosis of
      APL and the detection of residual disease are based on the t(15; 17)
      translocation. Treatment with a combination of ATRA and anthracycline-AraC
      chemotherapy has shown a higher rate of complete remission in APL. We report the
      case of a 71-year-old male with the rare microgranular variant of APL to
      illustrate these findings. The patient was treated with a combination of ATRA and
      Daunorubicin-AraC chemotherapy and achieved complete remission. He developed
      retinoic acid syndrome as a complication of therapy with ATRA. The methods for
      diagnosis, the molecular mechanisms in the oncogenesis of APL, rationale of
      treatment of APL with ATRA, complications of therapy and the new concepts in the
      treatment of ATRA-resistant APL are discussed.

PMID- 10073060
TI  - "Gag clauses" are still a danger to physicians.

PMID- 10073061
TI  - Heeding the brave messengers.

PMID- 10073062
TI  - 5 reasons why doctors should care about deformed frogs.

PMID- 10073063
TI  - Frog deformities. Do they signal a human health risk?

PMID- 10073064
TI  - The challenges of medical marriages.

PMID- 10073065
TI  - The combined internal medicine/pediatrics residency. U of M graduates fill a
      growing need.

PMID- 10073066
TI  - Community-based screening for childhood lead poisoning. Identification of risk
      factors and susceptible populations in Duluth.
AB  - The purpose of this matched case-controlled study was to identify local risk
      factors and susceptible populations for childhood lead poisoning in Duluth,
      Minnesota. We mailed questionnaires to the parents of 20 children with known
      elevated capillary lead levels > or = 10 micrograms/dL; 76 age-matched controls
      had capillary lead levels < 10 micrograms/dL. The study identified these risk
      factors for elevated capillary lead levels in children: not attending daycare,
      having nonwhite parents, living in rental property in central Duluth, and moving
      with family three or more times in the previous five years. We conclude that
      these risk factors are related to socioeconomics. Minority children and children
      living in poverty in the Duluth area should be screened for lead poisoning
      according to the Centers for Disease Control and Prevention screening guidelines
      for high-risk lead exposure.

PMID- 10073067
TI  - Physician licensing and the Americans with Disabilities Act. An update on the
      Minnesota Board of Medical Practice.

PMID- 10073068
TI  - It's cold and flu season on the screen.

PMID- 10073069
TI  - Pediatric pain relief in trauma.

PMID- 10073070
TI  - Chronic otitis media with effusion.
AB  - Chronic OME, which arises from a complex series of inflammatory events in the
      middle ear, affects approximately 5% to 30% of children. The mean duration of MEE
      is 16 to 20 weeks during the first 2 years of life. This condition is diagnosed
      best with pneumatic otoscopy and tympanometry. The risk of chronic OME is
      increased by environmental factors and characteristics of the child, including
      disease history. Approximately 70% of MEE are culture-positive, with
      approximately 50% of these yielding S pneumoniae, H influenzae, or M catarrhalis.
      However, antibiotic treatment of acute otitis media and OME has only a minimal
      effect on the long-term resolution of MEE. Research has shown that 70% of
      children who have chronic OME suffer mild-to-moderate hearing loss, so a child
      who has bilateral MEE for 3 months should undergo hearing evaluation. If the
      child has hearing impairment, referral to an otolaryngologist for myringotomy and
      tympanostomy tube insertion is a treatment option that the AHCPR recommends after
      4 months of effusion with hearing loss. Sequelae of chronic OME include deficient
      expressive language and poorer attention skills due to the temporary hearing loss
      associated with OME, high-frequency sensorineural hearing loss, tympanic membrane
      atrophy, perforation, retraction, atelectasis, and cholesteatoma.

PMID- 10073071
TI  - Gastrointestinal bleeding.

PMID- 10073072
TI  - Hepatitis A.

PMID- 10073073
TI  - Index of suspicion. Case 1. Diagnosis: respiratory paralysis.

PMID- 10073074
TI  - Index of suspicion. Case 2. Diagnosis: acute lymphoblastic leukemia.

PMID- 10073075
TI  - Index of suspicion. Case 3. Diagnosis: HIV infection.

PMID- 10073076
TI  - [Perioperative cardiac morbidity/mortality in the elderly patient].

PMID- 10073077
TI  - [Postoperative cardiac morbidity/mortality in high-risk elderly patients
      undergoing non-cardiac surgery].
AB  - OBJECTIVE: To analyze cardiac morbidity and mortality after major noncardiac
      surgery in high-risk elderly patients. PATIENTS AND METHOD: Retrospective study
      of patients 65 years old or older in the postoperative intensive care unit
      between January 1990 and September 1996, after major noncardiac surgery, with
      histories of known ischemic heart disease (IHD group) or with two or more
      coronary risk factors (CRF group). We analyzed age, number of risk factors, type
      of ischemic heart disease, type and nature of surgery and cardiac morbidity or
      mortality. RESULTS: Five hundred twenty-nine patients were studied. Mean age was
      72.1 +/- 5.1 years. The CRF group contained 366 patients (69.1%); the IHD group
      contained 163 (30.2%) patients with angina or histories of myocardial infarction.
      Rates of morbidity in the two groups were 10.1% and 25.8%, respectively (p <
      0.001); the cardiac death rates were 2.18% and 5.5%, respectively (p = 0.08). No
      effect of number of coronary risk factors, type of ischemic heart disease, or
      type of surgery was found. Emergency surgery was associated with greater
      morbidity (p < or = 0.0011 and p < 0.001, respectively) and mortality (p < 0.001
      in both groups). Age over 75 years was related to increased rates of morbidity (p
      = 0.003) and mortality (p = 0.031). CONCLUSIONS: In our practice elderly patients
      with known ischemic heart disease undergoing major noncardiac surgery suffer more
      postoperative cardiac complications than do those who only have coronary risk
      factors. Mortality, however, is similar. The only factors associated with
      increased morbidity and mortality are emergency surgery and age over 75 years.

PMID- 10073078
TI  - [Arrhythmias in the pulmonary exeresis postoperative period].
AB  - OBJECTIVES: To determine the frequency of episodes of cardiac arrhythmia during
      the period following elective exeresis of the pulmonary parenchyma
      (pneumonectomies, double and single lobectomies), and to study the temporal
      patterns of occurrence and the association of arrhythmia and certain risk
      factors. PATIENTS AND METHODS: Retrospective analysis of data recorded in the
      case histories of 100 patients admitted to the postoperative intensive care unit
      (PICU) between November 1991 and March 1995. RESULTS: We monitored changes in
      heart rate after surgery by continuous electrocardiography in 38 of the 100
      patients (38%). Changes were more common in certain subgroups: older patients,
      those with preoperative cardiovascular and electrocardiographic abnormalities,
      and those who needed prolonged postoperative mechanical ventilation. Most
      arrhythmias were supraventricular (97.3%), the most common being atrial
      fibrillation (55.3%). Most diagnoses of arrhythmia (87%) were made within the
      first three days after surgery. Several drugs were used for treatment, based on
      the diagnosing anesthesiologist's criteria. Digitalis was the drug most often
      prescribed. Seven patients (7%) died in the PICU. Three were discharged with
      atrial fibrillation with ventricular response of less than 100 beats per minute.
      Postoperative cardiac arrhythmia was a direct cause of death of only one patient,
      who had ventricular fibrillation upon admission to the PICU.

PMID- 10073079
TI  - [Preloading with 500 ml of Hartmann's solution lessens the incidence and severity
      of hypotension and reduces the need for ephedrine after epidural anesthesia in
      ambulatory patients].
AB  - INTRODUCTION: Fluid preloading to prevent hypotension after epidural anesthesia
      has been widely questioned, although few studies have been performed in
      outpatients. OBJECTIVE: To evaluate the incidence and severity of hypotension,
      and the need for vasoactive agents after epidural anesthesia in outpatients who
      did or did not receive fluid preloading. PATIENTS AND METHODS: Forty patients
      under 55 years of age (ASA I and II) undergoing general surgery on an outpatient
      basis were assigned randomly to two groups of 20 according to whether they were
      to receive loading with Hartmann's solution or not before epidural anesthesia.
      All received a similar epidural dose of 2% mepivacaine. Hypotension was defined
      as a decrease of 20% in systolic or mean blood pressure in comparison with
      baseline, or absolute pressures of < 90 and 60 mmHg, respectively. Hypotension
      was treated with 5 mg boluses of ephedrine. RESULTS: Fourteen patients in the non
      preloading group and 5 in the preloading group developed hypotension (p < 0.05).
      Hypotensive episodes were fewer in patients receiving preloading fluids (0.5 +/-
      1.2 versus 2.0 +/- 2.4; p < 0.05). The ephedrine dose required was higher in non
      preloaded patients than in preloaded ones (10.0 +/- 12.2 versus 2.6 +/- 6.3 mg; p
      < 0.05). Time until presentation of hypotension was longer for non-preloaded
      patients. CONCLUSIONS: For patients undergoing outpatient surgery, fluid
      preloading with 500 ml of Hartman's solution decreases both the incidence and
      severity of hypotension, as well as the need for vasoactive drugs after epidural
      anesthesia.

PMID- 10073080
TI  - [Obstetric anesthesia/analgesia in Spain. Study notes on its historical evolution
      during the 1st half of this century].
AB  - This historical review of obstetric analgesia-anesthesia in Spain covers the
      first half of the twentieth century. Following usual practice for researching
      medical history, we have performed an exhaustive review of Spanish medical
      literature published during the study period, followed by classification, study
      and critical analysis. We found that the first half of the century saw
      considerable change in the application of analgesic-anesthetic techniques for
      childbirth and obstetric procedures, indicating that practitioners were far from
      apathetic as had been obstetricians of the second half of the nineteenth century,
      who generally rejected any type of analgesia for use during labor and birth. The
      numerous techniques in vogue during that period under study are described,
      although analgesia-anesthesia by inhaled ether and chloroform was undoubtedly the
      most widely used by obstetricians until well into the 1950's.

PMID- 10073081
TI  - [Prolonged neuromuscular block after a single dose of vecuronium in a patient
      with undiagnosed polyneuropathy and steroid myopathy].
AB  - We report the case of a patient who had been receiving long-term corticoid
      therapy with undiagnosed polyneuropathy and steroid-related myopathy before
      experiencing prolonged neuromuscular blockade (lasting longer than 4 hours) after
      administration of a single dose of 0.08 mg/kg of vecuronium. Neuromuscular
      function was monitored by accelerometry with four-stimuli series. Many of the
      circumstances present in this case -such as prior administration of
      succinylcholine, the use of an inhaled anesthetic, kidney insufficiency and
      cyclosporin therapy- have been associated with increased duration of blockade
      induced by neuromuscular blockers, although durations reported have been shorter
      than that experienced by our patient. After electromyography and muscle biopsy,
      polyneuropathy and steroid-related myopathy were diagnosed. We conclude that
      neuromuscular blockers should be administered with extreme caution to patients
      with polyneuropathy and those undergoing long-term corticoid therapy, in order to
      prevent prolonged neuromuscular blockade.

PMID- 10073082
TI  - [Hyponatremia in the postoperative period after a neurosurgical tumor condition].
AB  - A four-year-old girl suffered difficult-to-diagnose hyponatremia resistant to
      treatment following surgery for a suprasellar tumor. The final diagnosis was
      diabetes insipidus evolving in three stages. Hyponatremia is a common problem
      following surgery to remove brain tumors. Early diagnosis and treatment of this
      electrolytic imbalance are essential for preventing serious neurological symptoms
      or death. The conditions most closely related to hyponatremia are inappropriate
      antidiuretic hormone secretion syndrome (IADHSS) and cerebral salt wasting
      syndrome (CSWS). The latter has become more common in recent years among patients
      undergoing brain surgery. Whereas IADHSS is treated by restricting fluids, CSWS
      requires administration of salt and volume fluid volume. We believe that for
      differential diagnosis of postoperative hyponatremia, a fluid restriction test
      takes priority over of fluid loading following neurosurgery. The course of
      hyponatremia must be carefully monitored and a complete endocrinological workup
      must be performed to detect the possible presence of hypophyseal deficiencies,
      particularly hypothyroidism and suprarenal insufficiency.

PMID- 10073083
TI  - [Intraparenchymal cerebral hematoma following the insertion of a catheter for
      monitoring intracranial pressure].

PMID- 10073084
TI  - [Rhabdomyolysis and compartment syndrome associated with drug abuse].

PMID- 10073085
TI  - [Diagnosis of Whipple's disease in a patient admitted to the intensive care unit
      with suspected hypovolemic shock].

PMID- 10073086
TI  - [Totally implantable venous systems and cardiac tamponade. Apropos of a case].

PMID- 10073087
TI  - [Anesthesia for the implantation of automatic defibrillators].

PMID- 10073088
TI  - [Coronary angioplasty: always a stent in arteries larger than 2.5 mm? The
      arguments pro].
AB  - Coronary stenting has provided better results than balloon angioplasty in terms
      of primary success and restenosis in previous randomized studies. These studies
      only included short coronary lesions located in vessels larger than 3 mm. Thus,
      these results can not be applied to complex lesions or those located in small
      vessels. In the present article we summarize our points of view regarding the
      current indications of coronary stenting in these types of lesions, where the use
      of this device may be still controversial. In all these situations the results of
      the stent seem to be better to those previously reported with balloon
      angioplasty. However, there is a percentage of patients treated by balloon
      angioplasty in whom a good immediate and long-term result can be obtained. The
      identification of patients with optimal result after balloon angioplasty need a
      postprocedure study of coronary flow reserve. The comparison of optimal balloon
      angioplasty (by angiographic and coronary flow reserve criteria) and stent, is
      the main objective of 2 studies that are currently under process. We will have to
      wait the results of these clinical trials to answer to the question if the
      implant of stents in all kind of lesions located in vessel larger than 2.5 mm is
      of proper use. Our current opinion is that coronary stenting is a safe and fast
      method of coronary transcatheter therapy in many types of coronary lesions and it
      may be considered the more efficient technique of percutaneous revascularization.

PMID- 10073089
TI  - [Coronary angioplasty: always a stent in arteries larger than 2.5 mm? The
      arguments con].
AB  - In the last 3 years there has been a tenfold increase in stent use during
      percutaneous coronary angioplasty. In many laboratories the prevailing strategy
      is to implant a stent whenever there are no contraindications to its use. The
      authors argue that this strategy of generalized stenting is not founded on solid
      scientific data, and that part of the actual growth in stent use is due to
      procedural reasons as simplicity, predictability and time economy. Accordingly
      they analyze the main trials comparing balloon angioplasty with elective stenting
      as well as the actual limitations and complications of stent use. Finally they
      point out alternative solutions to generalized stenting like the identification
      of subsets of patients who could benefit from stenting after balloon angioplasty
      (provisional stenting strategy).

PMID- 10073090
TI  - [The prognostic factors after an acute myocardial infarct treated with
      fibrinolytics].
AB  - BACKGROUND: The usefulness of the exercise test in evaluating patients with an
      acute myocardial infarction treated with fibrinolytics is controversial. On the
      other hand, the prognostic value of a patent infarct-related artery has not been
      clearly established. The objectives of this study were to assess the validity of
      the exercise test and to study the prognostic value of the artery patency after a
      myocardial infarction. MATERIAL AND METHODS: We studied 99 patients with a
      myocardial infarction treated with fibrinolytics, non-complicated. An exercise
      test and a cardiac catheterization were performed in the first month. The
      patients were followed-up for 2 years, recording the major cardiac events (death
      and reinfarction) and the minor events (angina class (II, left cardiac failure
      class (II or maintained ventricular tachycardia). RESULTS: On multivariate
      analysis with Cox regression, a workload < 4 METS at the exercise test was the
      only independent prognostic factor of major events (RR 5.6; CI 95% 1.68-19). The
      independent prognostic factors of minor events were: multivessel disease (RR
      3.36; CI 95% 1.56-7.24), anterior infarction (RR 3.15; CI 95% 1.3-7.6), abnormal
      exercise test (RR 2.98; CI 95% 1.46-6.09) and ejection fraction < or = 40% (RR
      2.48; CI 95% 1.07-5.74). The patency of the infarct-related artery was not a
      predictor of events. CONCLUSIONS: The exercise test is useful in predicting the
      prognosis in patients treated with fibrinolytics. An occluded infarct-related
      artery was not an independent predictor of cardiac events in 2 years of follow
      up.

PMID- 10073091
TI  - [The artery responsible for an infarct after thrombolysis: to see or not?].

PMID- 10073092
TI  - [Internal cardioversion with low-energy shocks in atrial fibrillation resistant
      to external electric cardioversion].
AB  - BACKGROUND AND OBJECTIVE: Although external electrical cardioversion is effective
      in most patients with atrial fibrillation, there are cases refractory to external
      cardioversion. This study is aimed at showing our initial experience with an
      internal cardioversion system in patients with previous unsuccessful external
      cardioversion. PATIENTS AND METHODS: Between February, 1997 and September, 1998
      nine consecutive patients with spontaneous chronic or persistent atrial
      fibrillation that failed external cardioversion, were included. Internal
      cardioversion was performed under sedation with two electrodes that had a 5.5 cm
      coil placed in the lateral right atrium and coronary sinus. Both electrodes were
      connected to an external defibrillator capable of delivering R-wave synchronized
      low-energy biphasic shocks following a minimum RR interval of 500 ms. Energy
      between 2 J and 10 J was applied until the restoration of sinus rhythm or a
      maximum of 2 shocks of 10 J. RESULTS: Sinus rhythm was achieved in the nine
      patients, but in two of them atrial fibrillation recurred after a few beats. Both
      had underlying structural heart disease. The other 7 patients, 5 of them without
      structural heart disease, were in sinus rhythm at discharge. No mechanic
      complications or ventricular arrhythmias were observed. Six patients are in sinus
      rhythm after 4 +/- 3 months of follow-up. CONCLUSIONS: Low-energy intracardiac
      cardioversion is useful in some patients with atrial fibrillation that had failed
      external cardioversion and can be performed without general anesthesia.

PMID- 10073093
TI  - [Aortic valve replacement with a pulmonary autograft (the Ross operation) in
      adult and pediatric patients. A preliminary study].
AB  - INTRODUCTION AND OBJECTIVES: Aortic valve replacement with the patients own
      pulmonary autograft (the Ross procedure) is by now, the best surgical method for
      the replacement of the diseased aortic valve in certain groups of patients, this
      is particularly true for young adults and children or neonates with complex left
      ventricular outflow tract obstructions. The procedure was described by Donald
      Ross in 1967, and many years have passed. So in view of the accumulated
      experience the indications have extended to a wide group of patients which
      include children, neonates and young adults with formal contraindications for
      anticoagulation. In this publication we present our experience and our
      preliminary results in a group of fifteen patients which include adult and
      pediatric. MATERIAL AND METHODS: In six patients the etiology of lesion was
      congenital and in the remainder nine the valve had an acquired lesion. Two
      patients had an open heart procedure before this operation both of them to
      relieve an obstruction to the left ventricular outflow tract. In this group of
      patients the Ross procedure was carried out inserting the pulmonary autograft in
      the aortic position as a total root which was always reconstructed with
      cryopreserved pulmonary homograft, the mean homograft diameter was 26.1 +/- 4 mm
      (19-35). RESULTS: In all patients a transesophageal echocardiogram was performed
      in the operating room and postoperative, 1 or 2 months later. Only in one patient
      a mild aortic regurgitation was detected, no significant transaortic or
      transpulmonary gradients were detected postoperative. One patient was reoperated
      for bleeding in the postoperative course, there was no hospital mortality in our
      group and all the patients had an uneventful postoperative period. In the short
      term follow-up (41-155 days). All the patients are free of anticoagulant therapy,
      all them are in New York Heart Association Functional Class I. CONCLUSIONS: The
      patients presented in this publication which include adult and pediatric, are the
      first group of patients operated in our country with some excellent preliminary
      results. We hope that this procedure will become popular and that other surgical
      groups will adopt it as another surgical tool to replace a diseased aortic valve.

PMID- 10073094
TI  - [The Ross operation].

PMID- 10073095
TI  - [The characteristics, management and prognosis of the acute myocardial infarct
      patient in the Valencian Community in 1995: the results of the PRIMVAC Registry
      (The Registry Project of Acute Myocardial Infarct in Valencia, Alicante and
      Castellon). As representatives of the PRIMVAC investigators].
AB  - BACKGROUND AND OBJECTIVES: Regional registers of patients with acute myocardial
      infarction are scarce in Spain. The PRIMVAC register (Proyecto de Registro de
      Infarto agudo de Miocardio de Valencia, Alicante y Castellon) was initiated to
      obtain updated information on the management of these patients in the Valencia
      Autonomous Community. Data of the first twelve months of the register are
      presented. METHODS: The 17 participating hospitals cover 2,833,938 inhabitants.
      Demographic, clinical, procedural and outcome data as well as predictive
      variables of mortality were analysed in the patients with acute myocardial
      infarction during their stay in the coronary care units from 1 December 1994 to
      30 November 1995. RESULTS: During 12 months, 2,377 patients were included. Mean
      age was 65.3 years (SD 11.9) and 23.2% were female. Left ventricular failure was
      present in 39.8%. Thrombolytic therapy was applied in 42.1% with a median time
      delay of 195 min from chest pain onset. This time was longer in the women (250
      min) and in the elderly (210 min). The in-coronary-care-unit-mortality rate was
      13.9%. Age, female gender, diabetes, previous myocardial infarction, Q wave and
      right ventricular infarction independently predicted increased early mortality.
      CONCLUSION: Present data show the feasibility of an acute myocardial infarction
      register in the Valencia Autonomous Community. Although an acceptable level of
      thrombolysis has been reached, the mortality rate is still high. The long delay
      in initiating thrombolysis, particularly in female and elderly patients is
      remarkable.

PMID- 10073096
TI  - [A giant left ventricular pseudoaneurysm secondary to an acute posteroinferior
      myocardial infarct].

PMID- 10073097
TI  - [Pericarditis secondary to the rupture of a hydatid cyst].
AB  - Cardiac hydatic cysts are rare and represent 0.5 to 2% of all hydatic cysts in
      humans, but usually associated with fatal complications. We report a case of a
      male 27 years old with a hydatid cyst located in left ventricle asymptomatic
      until rupture. It was diagnosed by two-dimensional echocardiogram in a control.

PMID- 10073098
TI  - [An anomalous origin of the left coronary artery associated with a right coronary
      spasm as the cause of angina and presyncope].
AB  - We describe the rare association of angina at effort and presyncope in a young
      patient with an anomalous origin of left coronary artery and associated coronary
      spasm in the normal right coronary artery. The patient did well under calcium
      channel blocker therapy after seven years of follow-up, which is in contrast with
      the usual recommended management of these patients.

PMID- 10073099
TI  - [A thrombus in the right atrium secondary to a fistulated aortic paravalvular
      abscess: apropos a case].
AB  - This report describes the two-dimensional echocardiographic and autopsy findings
      in a patient with aortic valve endocarditis complicated by a posterior aortic
      root abscess with rupture into the right atrium, creating an aortic-right atrial
      fistula, with a later development from the root of the fistula of a pediculated
      thrombus inside the cavity.

PMID- 10073100
TI  - [A double fistulous communication between the aortic root and both left cardiac
      chambers. Its diagnosis by multiplanar transesophageal echocardiography].
AB  - The case of a patient with mitral and aortic mechanical valve prostheses is
      presented who developed early postoperative infective endocarditis and,
      subsequently, a fistulous communication between the posterior aortic sinus and
      both the left atrium and the left ventricle. A diastolic murmur of apparent
      aortic prosthesis regurgitation was heard, although an abnormal aortic valve
      function could not be demonstrated in the transthoracic echocardiographic study.
      Instead, the presence of a systolic high velocity flow by continuous wave Doppler
      suggested prosthetic mitral leakage. The clinical presentation of progressive
      congestive heart failure and pulmonary hypertension by Doppler prompted a further
      study by means of transesophageal echocardiography with multiplanar probe showing
      the above mentioned double fistulous communication. The diagnosis was later
      confirmed by angiography and also at surgery.

PMID- 10073101
TI  - [Pulmonary artery aneurysm. A case report].
AB  - The pulmonary artery aneurysm is a rare clinical entity that presents a low
      incidence and prevalence, of difficult diagnosis to be presented with poorly
      specific symptoms or also without symptoms, being detected in radiological
      studies as a widening or mediastinal mass. It can be uni or bilateral and
      presenting itself isolated or in the context of other sicknesses. The diagnosis
      of certainty is based in the realization of Echo-Doppler and other studies as a
      tomography or a magnetic resonance, the therapeutic option being so difficult,
      and according to cases, by an expectant or aggressive attitude.

PMID- 10073102
TI  - [Mobile emergency services of Neuchatel. Evaluation of two years of activity:
      1996-7].

PMID- 10073103
TI  - [Pediatric emergencies: prehospital management].

PMID- 10073104
TI  - [Psychiatric emergencies: prehospital management].

PMID- 10073105
TI  - [Unstable angina: electrocardiographic changes suggesting a severe stenosis of
      the anterior interventricular artery].

PMID- 10073106
TI  - [Cross reaction allergies: what importance to the clinician?].

PMID- 10073107
TI  - [Hypoglycemic coma of long duration].

PMID- 10073108
TI  - [Endocarditis manifesting as a spondylodiscitis and psoas abscess].
AB  - The revealing of a bacterial endocarditis by a spondylodiscitis is relatively
      rare. Only 80 cases have been reported ever since De Seze's and his team's first
      publication in 1965. We report the case of a 59 year old women, hospitalized for
      a meningitis who presents signs of a spondylodiscitis and psoas abscess revealing
      an endocarditis. This case shows that one always have to search for an
      endocarditis when dealing with a spondylodiscitis. A thorough examination
      including a cardiac ultrasound is mandatory and a six weeks follow-up is
      necessary, since the prognosis depend mainly on the valvular disease.

PMID- 10073109
TI  - [Cardiac perforation by a gastric ulcer: an unusual cause of death, after an
      esophageal and gastric resection of an epidermoid esophageal carcinoma].
AB  - We report here the case of a 55 year old female that underwent surgery for a well
      differentiated squamous cell carcinoma of the esophagus (middle third). Four
      months after surgery, she complains of neck pain, for which she is prescribed non
      steroidal antiinflammatory drugs (NSAID). A CT-scan and a Barium swallow are then
      normal. After three weeks of treatment, the patient is admitted on emergency to
      the Intensive Care Unit for a resuscitation hematemesis and atrial fibrillation
      with a fast ventricular response. The symptoms are stabilized after the
      transfusion of a few packed red blood cells. A few hours later, however, a
      massive hematemesis recurs and the patient dies despite intense resuscitation
      measures. Autopsy reveals three gastric ulcers, one of which had perforated
      through the cardiac left ventricular wall.

PMID- 10073110
TI  - [Eosinophilic lung. A case report: diagnostic approach].
AB  - From a particular case of eosinophilic lung, we try to define a practical way to
      an easier diagnosis. We also review all the concerned pathologic entities and
      propose an aetiologic classification.

PMID- 10073111
TI  - [Risk taking users of an anonymous HIV screening center: trying to understand the
      psychodynamics].
AB  - This article shows the importance of the part of the unconscious, which has been
      under-estimated till now when users of a VIH anonymous depistage center are
      taking risks. Considering some clinical situations, we can underline the limits
      of the prevention campaigns, which can only be directed at groups and not at
      individuals. Most of the users have a good idea of the protection tools
      recommended through the preventive campaigns; the authors also describe the
      negative attitudes that therapeutist can feel towards persons who are seeking
      sexual satisfaction in risk behaviours.

PMID- 10073112
TI  - [Employment and protection of medical records].

PMID- 10073114
TI  - [Homeopathy].

PMID- 10073115
TI  - Combined effects of HIV-infection status and psychosocial vulnerability on mental
      health in homosexual men.
AB  - The present study examines psychiatric symptomatology and syndromal depression
      among 174 HIV+ and 760 HIV- homosexual men enrolled in the Pittsburgh site of the
      Multicenter AIDS Cohort Study (MACS). A central study goal was to determine
      whether men's psychosocial status in the areas of demographics, social supports,
      and coping, in combination with their HIV-infection status, was associated with
      mental health. Cross-sectional analyses indicated that HIV+ men had significantly
      higher levels of psychiatric symptomatology and syndromal depression than HIV-
      men. However, multivariate analyses showed that these associations only appeared
      among HIV+ men with certain psychosocial characteristics. HIV+ men who were
      younger, lacked full-time employment, claimed relatively high support from their
      relatives, and demonstrated high use of active behavioral coping strategies were
      at greater risk for psychiatric symptomatology and/or syndromal depression.
      Further, sense of mastery and frequent use of avoidant coping strategies were
      highly predictive of psychiatric outcomes irrespective of HIV status. The
      findings suggest that knowledge of an individual's HIV status per se will be
      inadequate for valid assessment of psychological risks. Rather, any association
      of HIV status and mental health will depend largely on other psychosocial
      characteristics that foster vulnerability or resistance to distress in these men.

PMID- 10073116
TI  - Life stress, social support and psychological distress in late adolescence: a
      longitudinal study.
AB  - Questionnaire data from 211 adolescents and follow-up data recorded 18 months
      later were employed to test main effects and stress-buffering effects of negative
      life events, on-going stressors and social support from family and friends on
      mental health. Negative life events, change from baseline level of on-going
      adversities and social support all contributed significantly to subsequent
      symptom scores, although negative life events only reached borderline
      significance among boys. There was evidence in favour of the buffer hypothesis
      for boys: negative life events had a significantly stronger effect when social
      support from peers was low, and long-lasting adversities had a significantly
      stronger effect when social support from parents was low. Both these two-way
      interaction effects among boys were significantly different from the
      corresponding trends among girls. Since the scores on both the independent and
      dependent variables are based on subjective self-reports, the results may have
      been affected by various types of response bias. The probabilities of such bias
      effects are discussed.

PMID- 10073117
TI  - The design of Partners in Care: evaluating the cost-effectiveness of improving
      care for depression in primary care.
AB  - This paper describes a study design that blends health services and clinical
      research approaches to examine the cost-effectiveness of treatments and of
      quality improvement for depression in primary care, managed care practices. Six
      managed care organizations in Los Angeles (Calif.), San Antonio (Tex.), San Luis
      Valley (Colo.), Twin Cities (Minn.), and Columbia (Md.) participated. Primary
      care clinics were randomized to one of two quality improvement interventions or
      care as usual. Interventions included patient and provider education, nurse
      assisted patient assessment, and resources to support appropriate medication
      management or access to cognitive behavioral therapy. Practices implemented the
      interventions with study support. Providers and patients selected treatment.
      Patients with depressive symptoms regardless of comorbidities were eligible. Over
      27,000 primary care patients visiting the practices of 181 primary care
      clinicians were screened for depression, 14% were potentially eligible, and 1356
      enrolled into the 2-year longitudinal study. Enrollees were similar to eligibles,
      but usual care clinic patients tended to be less severely depressed than
      intervention clinic patients, partly due to clinic staff enthusiasm. The result
      of the study showed that studying treatment effects and quality improvement in
      nonacademic settings is feasible, but requires relaxation of design features of
      experiments that protect internal validity. The trade-off between certainty of
      causal inference and generalizability to usual care conditions is discussed. The
      strengths and limitations of this study design are compared to those of clinical
      trials and recent clinical effectiveness studies.

PMID- 10073118
TI  - Psychiatric wills of mental health professionals: a survey of opinions regarding
      advance directives in psychiatry.
AB  - Psychiatric wills are advance directives for an eventual involuntary treatment in
      psychiatry. We attempted to determine psychiatric professionals' knowledge and
      opinion about this legal option and obtain their formulations of advance
      directives for themselves. A total of 101 psychiatric nurses and psychiatrists at
      the Department of Psychiatry of the University of Vienna responded to a
      questionnaire about psychiatric wills and anonymously drafted advance directives
      for themselves concerning psychiatric treatment in case of an acute psychosis.
      Fifty-four percent knew about this legal option, 55% considered it an appropriate
      legal possibility, and 29% considered it inappropriate. The study also found that
      75% of respondents reject certain methods of therapy, e.g. 30% want to exclude
      the use of neuroleptic medications, and 46% reject ECT. We conclude that although
      there is little experience so far with advance directives for psychiatric
      patients, there is an interest and predominance of positive attitudes towards
      this legal option among mental health professionals. Concerning their
      preferences, professionals felt inclined to make very specific statements as to
      which available treatment strategies they would reject and which they would
      request for their treatment. This bodes well for the widespread use of advance
      directives in mental health settings.

PMID- 10073119
TI  - What predicts the course of expressed emotion in relatives of patients with
      schizophrenia or related psychoses?
AB  - The expressed emotion (EE) index may not be as stable as it was once believed to
      be. The aim of this study was to identify variables associated with spontaneous
      change from low to high and from high to low levels of EE and EE subscales-
      critical comments (CC), hostility (H), emotional overinvolvement (EOI). Using a
      longitudinal, prospective study design, of 59 relatives having at least weekly
      face-to-face contact with 40 patients with an acute episode or relapse into
      schizophrenia (DSM-III-R) were interviewed by means of the Camberwell Family
      Interview (CFI) at admission and at 4 1/2 months after discharge. The results
      showed that high-high or unstable levels of CC, H or EE were associated with the
      patient not working or studying prior to admission. Relatives with low-high and
      high-high EOI patterns had more weekly face-to-face contact with the patient
      prior to admission than relatives with a low-low EOI pattern. Patients whose
      relatives had low-high CC and EE patterns were less ill at admission than
      patients whose relatives had low-low patterns. Higher perceived family burden was
      associated with, at admission, an unstable pattern of CC, and at follow-up, high
      high EOI or EE patterns rather than low-low patterns. Our study suggests that it
      is possible to identify which relatives will have a stable and which a changing
      EE level, allowing for more focused intervention.

PMID- 10073120
TI  - Self-reported depressive symptoms among Chinese adolescents.
AB  - Previous reports on the prevalence and features of depression among adolescents
      have been inconsistent. The purpose of the current study was to estimate the
      prevalence of depression among Chinese adolescents with a standardized
      instrument. A total of 2462 students, aged 13-22, were sampled from the Shandong
      province of China. The Zung Self-Rating Depression Scale (SDS) was administered
      to the subjects in their classrooms. It was shown that the mean SDS score was
      44.8 (SD 9.9) and it decreased significantly from the age of 18 upward (F =
      31.73, df = 9, P < 0.01). No significant difference was found between males and
      females (t = 0.70, P > 0.05). Taking 55 as a cut-off score, the prevalence rate
      of depression was 16.9% (95% CI = 15.4-18.4%). Logistic regression showed that
      increasing age appeared to decrease the risk for depression. Most of the
      individual items differed between ages, except for weight loss and constipation.
      Principal components factor analysis revealed that the characteristics of
      adolescent depression were depressive/anxious mood, psychomotor retardation, loss
      of self-esteem, somatic symptoms and decreased appetite and libido. Although the
      study was based on a large sample using an established instrument, the sample was
      not from a general adolescent population and case ascertainment was not by
      clinical diagnosis.

PMID- 10073121
TI  - Hostility and coping capacity as risk factors of elder mistreatment.
AB  - In the present study we investigate whether, in addition to established risk
      factors, some personality traits of the victims are associated with elder
      mistreatment. Identified victims of chronic verbal aggression (n = 37), physical
      aggression (n = 38) and financial mistreatment (n = 55) as well as equal-sized
      control groups were interviewed. The control groups were matched on age, gender,
      and the characteristics that have been identified as risk factors for the types
      of elder mistreatment listed above. All respondents were over 65 years of age. In
      a standardised interview, commonly used instruments were utilised to assess
      coping style, locus of control, perceived self-efficacy and hostility. To analyse
      the data multivariate logistic regression analyses were performed. The study
      found that, chronic verbal aggression was associated with having less control
      over problem situations and a higher tendency to react aggressively when feeling
      angry or frustrated. Physical aggression was associated with a passive and
      avoidant way of handling problems. Financial mistreatment was associated with
      having negative beliefs of self-efficacy and a tendency to turn aggression and
      frustration on themselves. These results indicate that in addition to the
      established risk factors, some personality traits of the victims have to be
      considered as risk factors of elder mistreatment. The way people handle problems
      makes them more or less vulnerable to becoming victims of elder mistreatment.
      Furthermore, the results indicate that elder mistreatment may be associated to
      some extent with long-standing interaction patterns among family members. These
      findings are important for prevention of an intervention in cases of elder
      mistreatment.

PMID- 10073122
TI  - The meaning and significance of caseness: the Hopkins Symptom Checklist-25 and
      the Composite International Diagnostic Interview. II.
AB  - In previous analyses of data from the present general population study we found
      that screening of anxiety and depression symptoms by the Hopkins Symptom
      Checklist-25 (HSCL-25) and diagnostic classification by the Composite
      International Diagnostic Interview (CIDI) identified the same amount of cases,
      but agreed in only half of them. In this paper we compared and validated the
      screening cases with the classificatory cases by the use of medication, loss of
      functioning and help seeking (illness indicators). We thought that the CIDI cases
      would have more illness indicators, because they reflected diagnoses, "true
      illness", in contrast to the HSCL-25, which was a more unspecific measure of
      distress. The HSCL-25 and the illness indicators data were collected in a stage I
      random individual population sample above 18 years during 1989-1991 (N = 1879,
      response rate 74%), the CIDI data were collected in a selected stage II, (N =
      606, response rate 77%). The stage II data were weighted to represent the
      population sample. Screening cases by the HSCL-25 had significantly more illness
      indicators than diagnostic cases by the CIDI. Cases agreed upon with both
      instruments had the most illness indicators, cases agreed upon only by the CIDI
      had the least. Diagnoses give information about help eventually needed, the HSCL
      25 distress measure expresses more the urgency with which it is needed. The
      choice between the HSCL-25 and the CIDI would depend on the aim and the resources
      of the study. If evaluation of needs is involved, using an instrument picking up
      both classification and distress would be the best choice. Given our positive
      experience with interviewing with the CIDI, a CIDI improved to be more sensitive
      to how much distress a certain diagnosis exerts on the individual would be a good
      choice.

PMID- 10073123
TI  - [Perforation of the colon during colonoscopy].
AB  - Perforation of the colon during colonoscopy for diagnostic or therapeutic
      purposes is an important but not a frequent complication. Bibliographic
      controversies exist upon the type of treatment either conservative or surgical.
      In the late years reported cases favorise a trial for conservative treatment
      under optimal clinical conditions. We report our late experience with 3 cases of
      iatrogenic colonic perforation treated laparoscopically. Direct visualisation of
      the local status, the possibility of simple colonic oversew, abdominal toilette
      and drainage are the advantages of the method on which it should be added the
      psychological comfort for the surgeon and his gastroenterologist.

PMID- 10073124
TI  - [Primary extramedullary plasmacytoma of the duodenum].
AB  - INTRODUCTION: Primary extramedullary plasmacytoma (EMP) is a solitary tumor that
      arises outside the bone marrow in patients without clinical evidence of
      coexisting multiple myeloma. EMP represents only 4% of all patients with plasma
      cell malignancies. The tumor generally occurs in the submucosal tissue of the
      upper airway or oral cavity. 10% of all EMP occur in the gastrointestinal tract.
      Only 8 cases of EMP in the duodenum have been reported in literature. METHOD: The
      authors present a case of EMP in the duodenum in a 53 year old men. The tumor was
      initially misdiagnosed as desmoid tumor. With a combined treatment of surgery and
      chemotherapy complete remission for 2 years was achieved, followed by a
      dissemination of the tumor in the testis, mandibular bone and ribs. CONCLUSION:
      EMP is a rare differential diagnosis of an intraabdominal tumor. Diagnosis is
      difficult, and in most reported cases it is confirmed only postoperatively after
      immunohistochemical staining. Combined treatment of surgery and chemotherapy seem
      to offer the best potential for cure.

PMID- 10073125
TI  - Periampullary carcinomas: a special entity of duodenal tumors.
AB  - DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as
      diagnosed earlier and having a better prognosis than other duodenal tumors.
      METHODS: In the present study, we retrospectively reviewed the medical records of
      16 patients with periampullary carcinomas over 10 years. RESULTS: 16 patients, 10
      men and 6 women (median age 66.7 years, range 42-80) had a malignant
      periampullary tumor. Initial symptoms were jaundice (88%), weight loss (69%),
      nausea and vomiting (50%) and abdominal pain (38%). Gastro-duodenoscopy, ERCP,
      ultrasound and CT scan were the most useful diagnostic tools. Histologically all
      the tumors were adenocarcinomas and solitary tumors. 91% were stage pT1 or pT2
      tumors, localized in the duodenal wall without any infiltration of the pancreas.
      36% of the tumors had metastasized either in lymph nodes or distant organs at
      diagnosis (18% pN1, 18% pM1). Resectability rate was 81%, curative resection was
      achieved in 62%. The operations performed were pancreatico-duodenectomy (n = 8),
      local tumor resection (n = 5) and palliative bypass (n = 3). Morbidity and
      reoperation rate were 37.5% and 18.8%, respectively; 30-day mortality was 0%. The
      1- and 5-year survival rates were 58.3% and 33.3%, respectively. CONCLUSIONS:
      Compared to carcinomas of the small bowel or the exocrine pancreas periampullary
      carcinomas have a far better 5-year survival rate of more than 30%. Aggressive
      diagnostic workup in case of the leading symptom jaundice and radical operative
      therapy are key factors to achieve this goal.

PMID- 10073126
TI  - [Extraovarian peritoneal serous papillary carcinoma: an unusual surgical case].
AB  - The extraovarian peritoneal serous papillary carcinoma (EPSPC) is a multicentric
      peritoneal tumor with minimal or absent involvement of the ovaries. The actual
      treatment regimen consists of a cytoreductive surgery followed by a combination
      chemotherapy. Few studies have compared outcome of EPSPC to papillary serous
      ovarian cancer (PSOC). Several authors have documented similar clinical behavior
      between EPSPC and PSOC, but this finding has not been universal. A 64-year-old
      female patient with symptomatic gall stone disease underwent elective
      laparoscopic cholecystectomy. Unexpectedly we found some uncommon small nodular
      structures on the serosa of the right colon. The histological findings suggested
      a poorly differentiated peritoneal serous papillary carcinoma. Biopsies of both
      ovaries showed no signs of tumor infiltration and the diagnosis of EPSPC was
      established. After surgery, a combination chemotherapeutic regimen with
      carboplatin and cyclophosphamid was given. Laparoscopic reassessment 7 months
      after the first procedure showed no tumor. 3 identical cycles completed
      chemotherapy. Normal ovaries and no other tumor sites were found in a final
      laparoscopic look after 11 months.

PMID- 10073127
TI  - Management of inflammatory abdominal aneurysms--immediate and late results.
AB  - INTRODUCTION: Despite progress in the technical approach to aneurysms,
      inflammatory aortic aneurysms (IAA) in particular present the surgical team with
      a unique challenge. This retrospective study investigates immediate and late
      results after surgical treatment of IAA. PATIENTS AND METHOD: Fifteen cases of
      IAA among 520 aneurysmectomies of the abdominal aorta were operated during the
      period 1986-1995. All the patients were males of a mean age of 66 years.
      Diagnosis was established on preoperative CT-Scan, gross appearance at surgery
      and histologically. CT scanning could detect the IAA in 13 of 15 cases. In 2
      cases MRI was diagnostic. Surgical treatment using the inlay method, constitutes
      the method of choice due to restricted dissection, as it reduces the possibility
      of iatrogenic injuries. RESULTS: None of the patients died during the first 30
      postoperative days. One patient died at the age of 78, 40 days after the
      operative procedure, due to a cerebral episode. Four to 120 months later 3
      patients had also died from cause unrelated to the operation and one more patient
      was lost on follow-up. The remaining 10 patients were free of symptoms without
      any progression of the fibrotic process in the CT scanning. We observed a total
      regression in 7 and partial regression in 3 patients without detecting any
      inflammatory findings or renal failure. CONCLUSION: IAA's are rare. CT and/or MRI
      establish the diagnosis preoperatively and contribute to the surgical program
      with immediate and late results equal to those found in arteriosclerotic
      aneurysms of the abdominal aorta.

PMID- 10073128
TI  - [Prevention of pericardial adhesions with a bioresorbable membrane].
AB  - A bioresorbable membrane made of sodium hyaluronate and carboxymethycellulose,
      has been reported to prevent peritoneal adhesion. This study was designed to test
      its efficiency in the prevention of pericardial adhesions. Two groups of six pigs
      (mean weight 72 +/- 8 kg) were chosen for the experiment. The heart was exposed
      through a left thoracotomy and a wide patch of pericardium was excised. In the
      test group (n = 6), the left ventricular area without pericardium was divided
      into two areas: area A where six stitches of Prolene were performed, and area B
      which was left intact. The membrane was applied on the both areas as well as on
      the adjacent area covered with pericardium (area C). In the control group (n =
      6), the same protocol was performed except for the membrane application. The
      animals were sacrificed one month later. The adhesion status as well as the
      visibility of the coronary anatomy was assessed according to severity scores
      ranging from 0 to 3 for the adhesions and from 0 to 2 for the visibility. The
      difference between groups was considered significant when p < 0.05. The adhesion
      score of the area A was 1.7 +/- 0.5 in the test group versus 2.5 +/- 0.5 in the
      control group (p = 0.02) and the visibility score was 1.3 +/- 0.8 and 2 +/- 0
      respectively (p = 0.07). In the area B, the adhesion score was 1 +/- 0 in the
      test group versus 2 +/- 0.6 in the control group (p = 0.03) and the visibility
      score was 0.7 +/- 0.5 and 2 +/- 0 respectively (p = 0.001). Lastly, in the area
      C, the adhesion score was 1 +/- 0 in both groups (n.s.) and the visibility score
      was 0.7 +/- 0.4 in the test group versus 0.5 +/- 0.5 in the control group (n.s.).
      In this animal model, the role of the bioresorbable membrane in the prevention of
      pericardial adhesions is limited to the areas without pericardial cover and
      without foreign material. The presence of foreign material neutralizes its
      effect.

PMID- 10073129
TI  - The real incidence of percutaneous injuries in the operating room--a prospective
      study.
AB  - Despite the frequent exposure of operating room personnel to blood and other body
      fluids and the obvious risk of occupational transmission of HIV infection, the
      real incidence of injuries after needle sticks or cuts in the operating room has
      not been well investigated. Every injury occurring in the operating room during
      one thousand consecutive elective and emergency procedures was studied and the
      risk for acquiring an HIV infection was calculated. There were 50 injuries during
      761 elective procedures (6.6%) and 23 injuries during 239 emergency operations
      (9.6%). There was one single injury during 91 minimally invasive endoscopical
      procedures (1.1%). The surgeon was the person most frequently injured (3.5%). The
      injury rate of the scrub nurse varied between 1.4% and 2.8% according to the
      surgeon's experience. The operating room personnel is at risk for an occupational
      transmission of blood born pathogens. If the seroprevalence of HIV in surgical
      patients is estimated at 0.4% the calculated probability for a surgeon to acquire
      HIV infection over a 30-year career amounts to 0.3%.

PMID- 10073130
TI  - [Primary surgical care of pelvic fractures associated with perineal laceration].
AB  - Unstable fractures of the pelvic ring, associated to perineal lacerations are
      severe injuries occurring during high-energy trauma. High rates of septic
      complications and mortality have been reported with these injuries. Current
      treatment guidelines, while dealing with open pelvic fractures or dislocations
      are discussed, based on a current review of the literature and on our local
      experience. At our institution, 55 unstable type B or C fractures of the pelvic
      ring were treated by osteosynthesis between 1991 and 1997. Of these, 11 patients
      presented with an associated perineal laceration (20%). Simultaneously to the
      immediate pelvic ring fixation, a diversion colostomy was performed in all these
      patients. Repeated wound debridements and wide spectrum antibioprophylaxis were
      associated. Of these 11 patients presenting an open pelvic fracture, only one
      died of pelvic sepsis at three weeks. 10 patients survived (91%) and went on to
      bony union, without any local infectious complications. Aggressive
      multidisciplinary initial surgical management is a rule when dealing with this
      type of injuries, immediate colostomy and careful wound debridement must be
      associated to the initial osteosynthesis.

PMID- 10073131
TI  - Relationships between the lipophilicity of some 1,4-piperazine derivatives of
      aryloxyaminopropanols and their beta-andrenolytic activity.
AB  - Nineteen 1,4-piperazine derivatives of aryloxyaminopropanol were evaluated with
      respect to beta-adrenolytic activity. The retention factors obtained from HPLC,
      RM values obtained from partition TLC and the lipophilic Hansch's (4) constants
      pi were determined and the compounds were studied with respect to their
      lipophilicity based on chromatographic properties. The study of the influence of
      different substituents introduced at the para position on the phenyl ring on the
      retention factor indicated the log k vs. the number of carbon atoms in R1
      substituent to be a linear relationship. Attempts have been made to relate the
      beta-adrenolytic activity to the lipohydrophilic parameters by deriving a
      quantitative relationship between them. Significant parabolic correlation was
      observed between the beta-adrenolytic activity and the logarithm of the retention
      factor, log k. An analogous relationship was obtained between the beta
      adrenolytic activity of the compounds and the RM values obtained from partition
      TLC as well as Hansch's lipophilic constants pi.

PMID- 10073132
TI  - A study of local anaesthetics. Part 148. Influence of auxiliary substances on the
      surface tension, distribution coefficient and pharmaceutical availability from
      solutions of the potential drug VII.
AB  - The influence of auxiliary substances of the polyol group (glycerol, propylene
      glycol, sorbitol) and of their concentration (5, 10, 15 and 20% by weight) upon
      surface tension, distribution coefficient and pharmaceutical availability from
      solutions of the potential drug VII, viz., N-[2-(2-propoxyphenylcarbamoyloxy)
      ethyl] piperidinium chloride was studied. The substances were applied as hydrogel
      humectants. It was found that their influence on the surface tension,
      distribution coefficient and pharmaceutical availability from solutions of the
      potential drug VII depended on the type as well as concentration of the auxiliary
      substance. From the viewpoints of use in formulations of the drug form, sorbitol
      used at 5 and 10% concentrations represented the optimum.

PMID- 10073133
TI  - Determination of the lipophilicity of active anticonvulsant N-substituted amides
      of alpha-arylalkylamine-gamma-hydroxybutyric acid.
AB  - The lipophilicities of fourteen anticonvulsant active N-substituted amides of
      alpha-arylalkylamine-gamma-hydroxybutyric acid [I-XIV] have been determined by
      reversed-phase thin-layer chromatography with a mixture of methanol, TRIS buffer,
      and acetic acid as the solvent system. The RM value of each compound decreased
      linearly with increasing concentration of methanol. The partition coefficients
      (log P) of the amides were calculated by use of the Prolog P module of the Pallas
      system. Comparison of RM and log P enabled clog P values to be calculated. It was
      found that the anticonvulsant activity of amides [I-XIV] can be explained on the
      basis of their lipophilicity.

PMID- 10073134
TI  - 2-mercapto N-(azolyl)benzenesulfonamides. VI. Synthesis and anti-HIV activity of
      some new 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives
      containing the 1,2,4-triazole moiety fused with a variety of heteroaromatic
      rings.
AB  - A series of 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives
      containing the triazole moiety fused with a variety of heteroaromatic rings [XVI
      XXVIII] was obtained by the reactions of 3-methylthio-1,4-2-benzodithiazine 1,1
      dioxide derivatives [Ia-d] with 2-hydrazines [IIa-f]. Some of the intermediate
      1,1-dioxide-1,4,2-benzodithiazin-3-ylhydrazines [III-XV] initially formed were
      also isolated. Preliminary screening data indicated that compounds [XVI-XIX and
      XXVII] were anti-HIV inactive, whereas other compounds showed a high [XXI and
      XXIII], fairly high [XXIII and XXVI] or moderate [XX, XXIV, XXV and XXVIII]
      activity. The compound [XXI] exhibited also high activity against ten selected
      HIV mutants.

PMID- 10073135
TI  - Synthesis, anti-HIV and anticancer activities of new 4-(2
      mercaptobenzenesulfonyl)perhydro-1,2,4-triazin-3-ones.
AB  - Syntheses of N-(6-chloro-1,1-dioxo-7-R1-1,4,2-benzodithiazyn-3-yl)-N'-(2-
      hydroxyethyl)hydrazines (IIa-d], N-(6-chloro-1,1-dioxo-7-methyl-1,4,2
      benzodithiazyn-3-yl)-N'-(2- chloroethyl)hydrazine [IV], 4-(4-chloro-5-R1-2
      mercaptobenzenesulfonyl)perhydro-1,2,4-triaz in-3-ones [IIIa-d] and 5-chloro-4
      methyl-2-(3-oxoperhydro-1,2,4-triazin-4- ylsulfonyl)phenylthioacetic acid [V]
      have been described. Preliminary screening data have indicated that compounds
      [IIIa-d] exhibit either a moderate or a high anti-HIV activity and a moderate
      anticancer activity in some human tumor cell lines.

PMID- 10073136
TI  - Synthesis and anticonvulsant activity of 1,2-aminoalkanol derivatives.
AB  - A series of 1,2-aminoalkanol derivatives were prepared and evaluated for
      anticonvulsant activity in the maximal electroshock seizure (MES) and
      subcutaneous pentylenetetrazole seizure threshold (scMet) assays and for
      neurotoxicity (TOX). Most interesting were the anticonvulsant results of S-(+)-2
      amino-1-butanol derivative VIII, which displayed anti-MES activity with a
      protective index (TD50/ED50) of 4.55 corresponding with that for phenytoin,
      carbamazepine and valproate.

PMID- 10073137
TI  - Cage dimeric 4-aryl-1,4-dihydropyridines as promising lead structures for the
      development of a novel class of HIV-1 protease inhibitors.

PMID- 10073138
TI  - Synthesis and evaluation of 2 beta-oxyimino and alkenylpenicillanic acid sulfone
      derivatives as beta-lactamase inhibitors.
AB  - The synthesis and in vitro synergies of 2 beta-alkenyl and oxyiminopenam sulfone
      derivatives are described. Most of the compounds synthesized exhibited good
      inhibitory activities and synergistic antibacterial activities with piperacillin
      and ceftriaxone, respectively, against several beta-lactamase producing strains.
      Particularly the 2 beta-alkenylpenam sulfone derivatives. 1e and 1g, showed good
      synergistic activity with ceftriaxone against Citrobacter freundi NIH 10018-68
      and Proteus vulgaris 20. Also the compounds 2a, 2c, and 2f, 2 beta-oxyiminopenam
      sulfone derivatives, exhibited improved synergistic activity with piperacillin
      against Citrobacter freundi NIH 10018-68.

PMID- 10073139
TI  - Synthesis and analgesic activity of some deaza derivatives of anpirtoline.
AB  - New deaza derivatives of anpirtoline have been synthesized by three different
      methods. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity
      (hot plate, acetic acid induced writhing) have been studied.

PMID- 10073141
TI  - 10-alpha-Aminoacyl-9(10H)-anthracenones: inhibition of 12(S)-HETE biosynthesis
      and HaCaT cell growth.
AB  - 1,8-Dihydroxy-9(10H)-anthracenones with a 10-alpha-aminoacyl group were
      synthesized using either a mixed-anhydride coupling method or Boc-protected
      oxazolidinediones. The novel anthracenones were evaluated as inhibitors of the
      biosynthesis of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) in epidermal
      homogenate of mice and for inhibition of the growth of HaCaT keratinocytes. These
      cells were also tested for their susceptibility for the action of the most potent
      members of this series on plasma membrane integrity, in order to confirm that
      inhibition of cell growth is not a result of membrane damage induced by
      prooxidants released from anthracenones. Hydroxyl-radical generation as measure
      of the prooxidant potential of the compounds was determined by deoxyribose
      degradation. The most potent analogues of this series were equally potent as
      anthralin against 12(S)-HETE biosynthesis and keratinocyte proliferation, while
      oxygen-radical generation and the resulting damage to cell membrane was strongly
      reduced as compared to the antipsoriatic drug.

PMID- 10073140
TI  - Synthesis and antitumor activity of some new substituted quinolin-4-one and 1,7
      naphthyridin-4-one analogs.
AB  - The synthesis of some new analogs of quinolin-4-one and 1,7-naphthyridin-4-one is
      described. The prepared compounds were tested for their in vitro antitumor and
      cdc2 kinase or cdc25 phosphatase inhibitory activity. Compound ethyl 7-oxo-2,3
      dihydro-7H-pyrido [1,2,3-de][2,3-b]pyrido-1,4-thiazine-6-carboxylate (6b) showed
      antitumor activity against CNS SNB-75, breast T-47D, and lung NCI-H522 cancer
      cell lines with GI50 values of 8.3, 17.6, and 22.7 microM, respectively.
      Meanwhile, the compounds ethyl 4-oxo-8-phenylthio-1H,4H-quinoline-3-carboxylate
      (11a) and 4-oxo-8-phenylthio-1H,4H-1,7-naphthyridine-3-carboxylic acid (12b) have
      proved to be cdc25 phosphatase inhibitors at IC50 values of 11 and 5 microM,
      respectively.

PMID- 10073142
TI  - How can we predict and prevent the occurrence of therapy-related leukemias?

PMID- 10073143
TI  - No mutations of the Smad2 gene in human sporadic gastric carcinomas.
AB  - BACKGROUND: The majority of cancer cells escape from TGF-beta-mediated growth
      control. However, the mechanism of resistance to the growth inhibitory effects by
      TGF-beta is not clear. TGF-beta signaling is initiated when the type I receptor
      phosphorylates the SMAD proteins, Smad2 and Smad3. Recently, mutations of Smad2
      have been detected in human colon and lung cancers. Mutation of coding sequences
      of Smad2 in gastric carcinomas has not yet been elucidated adequately. METHODS:
      PCR-SSCP analysis of the entire coding region of Smad2 in 35 human sporadic
      gastric cancers and eight gastric cancer cell lines was performed using 11 sets
      of intron-based primers. RESULTS: No mutations of Smad2 were detected in any
      tumor or cell line. CONCLUSIONS: The results suggest that mutation of Smad2 does
      not play a key role in human stomach carcinogenesis.

PMID- 10073144
TI  - Natural history of fibroadenomas based on the correlation between size and
      patient age.
AB  - BACKGROUND: Several recent studies have reported that most fibroadenomas remain
      static or regress when they are managed conservatively; however, no such studies
      have evaluated the breast disorder in Japanese women. To understand the natural
      history of fibroadenomas in Japanese women, we examined the correlation between
      the sizes of the fibroadenomas and the women's age. METHODS: Fifty-eight
      consecutive patients (age range, 17-51 years; mean, 33.9 years) with
      histologically confirmed fibroadenoma were enrolled in this study. The sizes of
      the excised fibroadenomas were analyzed in relation to the women's ages. RESULTS:
      The fibroadenomas decreased significantly in size (Y, mm) with patient age (X,
      years) (P = 0.0012) according the equation Y = -0.340X + 27.0 (95% confidence
      limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of
      the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm
      (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8
      22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The
      mean annual decrease in the size of the fibroadenomas was 0.340 mm. CONCLUSIONS:
      Our results indicate that in Japanese women fibroadenomas increase in size more
      frequently in younger than in older women. Moreover, it is speculated that most
      fibroadenomas might stop growing when they reach an approximate maximum diameter
      of 20 mm, after which time they might remain static or regress.

PMID- 10073145
TI  - Initial experience with sentinel node biopsy in breast cancer at the National
      Cancer Center Hospital East.
AB  - BACKGROUND: Axillary lymph node dissection is an important procedure in the
      surgical treatment of breast cancer. Axillary lymph node dissection is still
      performed in over half of breast cancer patients having histologically negative
      nodes, regardless of the morbidity in terms of axillary pain, numbness and
      lymphedema. The first regional lymph nodes draining a primary tumor are the
      sentinel lymph nodes. Sentinel node biopsy is a promising surgical technique for
      predicting histological findings in the remaining axillary lymph nodes,
      especially in patients with clinically node-negative breast cancer, and a
      worldwide feasibility study is currently in progress. METHODS: Intraoperative
      lymphatic mapping and sentinel node biopsy were performed in the axilla by
      subcutaneous injection of blue dye (indigocarmine) in 88 cases of stage 0-IIIB
      breast cancer. Sentinel lymph nodes were identified by detecting blue-staining
      lymph nodes or dye-filled lymphatic tracts after total or partial mastectomy.
      Finally, axillary lymph node dissection was performed up to Levels I and II or
      more. RESULTS: Sentinel lymph nodes were successfully identified in 65 of the 88
      cases (74%). In the final histological examination, the sentinel lymph nodes in
      40 cases were negative, including four cases with non-sentinel-node-positive
      breast cancer (specificity, 100%; sensitivity, 86%). In nine (31%) of the 29
      cases with histologically node-positive breast cancer, the sentinel lymph nodes
      were the only lymph nodes affected. Axillary lymph node status was accurately
      predicted in 61 (94%) of the 65 cases. CONCLUSIONS: Although it was the initial
      experience at the National Cancer Center Hospital East, sentinel node biopsy
      proved feasible and successful. This method may be a reasonable alternative to
      the standard axillary lymph node dissection in patients with early breast cancer.

PMID- 10073146
TI  - Biochemical markers of bone turnover in breast cancer patients with bone
      metastases: a preliminary report.
AB  - BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the
      disease activity of metastatic bone tumor. In the present study six biochemical
      markers were evaluated to determine appropriate markers for the detection of
      metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover
      markers was assessed in 11 normocalcemic patients with bone metastases from BC
      and in 19 BC patients without clinical evidence of bone metastases. Bone
      formation was investigated by measuring serum bone isoenzyme of alkaline
      phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I
      procollagen (PICP): Bone resorption was investigated by measuring serum carboxy
      terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline
      (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and
      menopausal status. Significant correlations were observed between each of bone
      turnover markers except between BALP and OC. The mean levels of the six bone
      turnover markers were higher in patients with bone metastases than in those
      without them and significance was observed except for OC. The best diagnostic
      efficiency by receiver-operating characteristic (ROC) analysis was provided by
      ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed
      between ICTP and OC. Multiple logistic regression analysis adjusted by age
      revealed that the only significant marker related to bone metastases was ICTP.
      CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from
      BC. However, to reveal the clinical usefulness of these markers, further
      examination will be needed to account for the ease and cost-effectiveness of the
      measurements.

PMID- 10073147
TI  - A phase I/II study of continuous intra-arterial chemotherapy using an implantable
      reservoir for the treatment of liver metastases from breast cancer: a Japan
      Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group.
AB  - BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there
      are some reports of good response rates of hepatic metastasis from breast cancer
      by hepatic intra-arterial infusion chemotherapy, no phase I study including
      pharmacokinetic analysis has been reported. We performed a phase I/II study of
      intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find
      the maximum tolerated dose and response rate in patients with advanced or
      recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port
      was inserted into the proper hepatic artery. Patients received 30 mg/m2
      adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at
      level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1
      through day 14 every 28 days. At least two cycles were required before
      evaluation. Twenty-eight patients were entered into this study and 26 patients
      were evaluable. Seventeen patients had hepatic metastasis only, although nine
      patients had additional metastasis to other sites. RESULTS: Dose-limiting
      toxicity of thrombocytopenia and neurotoxicity occurred at level 4.
      Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in
      three (12%) and anemia in two (8%) patients. There were 11 catheter-related
      complications which were not dose dependent. Seven out of 13 evaluable patients
      (54%) responded at level 3. The median duration of response was 5.8 months
      (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+).
      CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective
      but catheter-related complications must be overcome before starting a phase III
      trial.

PMID- 10073148
TI  - Therapy-related leukemia and myelodysplastic syndrome in breast cancer patients
      treated with cyclophosphamide or anthracyclines.
AB  - BACKGROUND: Accumulation of data regarding therapy-related leukemia (TRL) or
      myelodysplastic syndrome (t-MDS) is critical for assessing the risk of developing
      such diseases and for subsequent decision-making processes for better treatment.
      METHODS: We evaluated the clinical characteristics of patients with TRL/t-MDS
      diagnosed at the National Cancer Center Hospital between January 1989 and
      September 1997. This report is concerned with those patients who initially had
      been treated with chemotherapeutic agents for breast cancer. RESULTS: Thirteen
      patients (median age, 55 years) developed TRL (n = 4) or t-MDS (n = 9). The
      median interval between the development of TRL/t-MDS and initial treatment was 94
      months (range 23-190 months). For the primary therapy, all patients had received
      intense and prolonged treatment with cyclophosphamide (CPA) and/or anthracyclines
      including doxorubicin (DOX), with a median cumulative dose of 55 g/body (range
      16.4-288.5 g) for CPA and 480 mg/m2 (range 395-625.5 mg/m2) for DOX. Seven
      patients were subsequently treated by chemotherapy and one received an allogeneic
      bone marrow transplantation. CONCLUSIONS: Clinicians must remain alert to the
      risks associated with unproven medical practices which include long-term
      administration of alkylating agents. Selected patients with TRL/t-MDS may respond
      to intense salvage combination chemotherapy.

PMID- 10073149
TI  - ESHAP as salvage therapy for refractory non-Hodgkin's lymphoma: Taiwan
      experience.
AB  - BACKGROUND: The ESHAP regimen, a combination of the chemotherapeutic drugs
      etoposide, methylprednisolone (solumedrol), high-dose cytarabine (ara-C) and
      cisplatin, has been shown to be active against refractory non-Hodgkin's lymphoma
      in therapeutic trials. We were interested in determining whether this regimen
      would be effective and tolerable for Chinese patients. METHODS: Thirty-two
      patients with refractory/relapsed non-Hodgkins lymphoma (23 intermediate-grade
      and nine high-grade) were enrolled in this study. Etoposide was administered at a
      dose of 40 mg/m2/day as a 1 h intravenous infusion from day 1 to day 4,
      solumedrol 500 mg/day was given as a 15 min intravenous infusion from day 1 to
      day 5, ara-C 2 g/m2 was given as a 2 h intravenous infusion on day 5 and
      cisplatin was given at a dose of 25 mg/m2/day as a continuous infusion from day 1
      to day 4. Clinical efficacy and toxicity were assessed on the basis of the WHO
      criteria. RESULTS: Ten patients (31.3%, 95% Cl 15.2-47.4%) attained complete
      remission (CR) and seven had partial remission (PR). The overall response rate
      was 53.1% (95% Cl 35.8-70.4%). In eight of the 10 CR patients, the remission
      lasted for more than 8 months. The remaining two patients had CR of 5 and 6
      months. The median duration of CR was 12.2 months (range 5-22 months).
      Myelosuppression with subsequent infections was the major toxicity. Severe
      leukopenia (WBC < 1000/microliter) lasted for an average of 12 days and
      thrombocytopenia (< 25,000/microliter) 18 days. One patient (3.1%) died of
      neutropenia-associated sepsis within 4 weeks after treatment. Non-myeloid
      toxicities included alopecia in 66% (28% grade 2, 22% grade 3), stomatitis in 72%
      (25% grade 2, 28% grade 3, 13% grade 4), hepatotoxicity in 9% (3% grade 2), renal
      toxicity in 13% (6% grade 2, 3% grade 3) and infection in 56% (18% grade 2, 25%
      grade 3, 13% grade 4). The majority of the responders relapsed within 2 years
      after ESHAP treatment. Median survival for all patients was 8.6 months.
      CONCLUSIONS: ESHAP is an active and tolerable regimen in Chinese patients with
      relapsed/refractory lymphoma, but the duration of remission is brief and without
      significant impact on survival.

PMID- 10073150
TI  - Validity and reproducibility of a quantitative food frequency questionnaire for a
      cohort study in Japan.
AB  - BACKGROUND: A self-administered quantitative food frequency questionnaire (Qx)
      was developed for a population-based cohort study on cancer in Takayama, Japan.
      METHODS: The Qx was tested among 58 male and 59 female volunteers. Average daily
      nutrient intakes for the previous year calculated from the Qx were compared with
      those from 3-day food records and four 24-h recalls. The Qx was also validated
      among 37 volunteers by comparing the nutrient intakes calculated from the Qx with
      12 1-day food records during a year. We also calculated the intra-class
      correlation coefficients for various nutrients between the Qx and the second Qx
      administered by the same volunteers 1 year after the first survey. RESULTS:
      Pearson correlation coefficients between total energy from the Qx and 3-day
      records were 0.38 for men and 0.25 for women and those between the Qx and 24-h
      recalls were 0.19 and -0.02 for men and women, respectively. Correlations between
      the several nutrients from the Qx and 3-day records ranged from 0.2 to 0.5 for
      both men and women. These correlations after energy adjustment ranged from 0.2 to
      0.6 for men and from 0.1 to 0.7 for women. In general, the correlations for
      various nutrients between the Qx and 12 1-day records were higher than those
      described above. The intra-class correlation coefficients ranged from 0.46 to
      0.78 in men and from 0.36 to 0.67, except for vitamin C in women. When the
      information on portion size was excluded, almost all of the above indices showed
      somewhat lower figures. CONCLUSION: These results suggest that our food frequency
      questionnaire with portion size information can be used to estimate nutrient
      intakes of each individual.

PMID- 10073151
TI  - A case of long-term survival with stage IV small cell lung cancer and early-stage
      central-type squamous cell lung cancer treated by photodynamic therapy.
AB  - The present report is on a 67-year-old man with stage IV small cell lung cancer
      and early-stage centrally located squamous cell cancer of the lung. He was
      diagnosed as small cell lung cancer with multiple metastasis to the ipsilateral
      lung and was found to have a central-type early-stage squamous cell cancer by
      bronchoscope. After obtaining a complete response to the small cell lung cancer
      with chemotherapy and radiotherapy, photodynamic therapy was applied to the
      squamous cell carcinoma, resulting in complete disappearance of the tumor.
      Recurrence of small cell cancer occurred at the ipsilateral lung and this patient
      died of small cell cancer 8 years after initiation of treatment. Post mortem
      examination confirmed complete disappearance of squamous cell cancer treated by
      photodynamic therapy. This is a rare case of long-term survival with stage IV
      small cell lung cancer and early-stage central-type squamous cell lung cancer
      successfully treated by photodynamic therapy.

PMID- 10073153
TI  - First lung transplant from living donors in Japan.

PMID- 10073154
TI  - Age-standardized cancer incidence rates in Japan.

PMID- 10073152
TI  - Spinal epidural abscess associated with epidural catheterization: report of a
      case and a review of the literature.
AB  - We describe a 53-year-old man who developed a catheter-related epidural abscess 8
      days after left upper lobectomy for lung cancer. Methicillin-resistant
      Staphylococcus aureus (MRSA) was detected in a culture of the epidural pus.
      Magnetic resonance imaging was essential for the diagnosis of epidural abscess
      and for determining the extent of spread. The patient was treated by laminectomy
      and administration of appropriate antibiotics, with almost complete recovery,
      except for urinary retention. A literature search yielded 29 additional cases of
      catheter-related epidural abscess. The median duration of catheterization was 4
      days and the median time to onset of the clinical symptoms after catheter
      placement was 8 days. Eleven of the 30 patients had some underlying disorders,
      including malignancy or herpes zoster, or were receiving steroids. Nine of the 10
      patients with thoracic epidural abscess had persistent neurological deficits,
      whereas 12 of the 15 patients with lumbar epidural abscess showed a full recovery
      after treatment. Surgical decompression was not required in six patients without
      significant neurological deficits, who recovered following antibiotic treatment
      (four patients) or percutaneous drainage (two patients). Thoracic catheters are
      associated with a disproportionately high incidence of epidural abscess and
      persistent neurological sequelae following treatment.

PMID- 10073155
TI  - Optimising ambulatory diabetes care in the information age: primary care,
      secondary care or integrated care?

PMID- 10073156
TI  - Recommendations on population screening for colorectal cancer in New Zealand.
      Members of the National Health Committee Working Party on Population Screening
      for Colorectal Cancer.
AB  - The National Advisory Committee on Health and Disability invited a working party
      to make recommendations on population screening for colorectal cancer in New
      Zealand. Recent results from randomised controlled trials of screening with
      guaiac faecal occult blood tests have provided evidence that population screening
      could reduce mortality from colorectal cancer. However, given the modest
      potential level of benefit, the considerable commitment of health sector
      resources, and the small but real potential for harm, the working party does not
      recommend population screening for colorectal cancer with faecal occult blood
      tests in New Zealand. The working party does nto recommend pilot colorectal
      cancer screening programmes in New Zealand because pilot programmes cannot
      address the issues of concern: the modest potential benefit and the small, but
      real, potential for harm. The working party does not recommend faecal occult
      blood testing as a screening test for colorectal cancer in average-risk
      individuals outside a population screening programme. Those requesting screening
      by faecal occult blood test should be given information about the potential risks
      and benefits. Follow-up bowel investigations in the public health system cannot
      be guaranteed without an increased allocation of resources. As there is yet no
      evidence from randomised controlled trials that screening with flexible
      sigmoidoscopy, colonoscopy or double-contrast barium enema produces a reduction
      in colorectal cancer mortality, the working party does not recommend population
      screening with these modalities. Wider consultation and further consideration
      should be undertaken to develop appropriate advice on surveillance
      recommendations for groups identified to be at increased risk of colorectal
      cancer. These decisions should be reviewed as evidence of benefit from new types
      of faecal occult blood test and other screening modalities becomes available. The
      working party recognises that colorectal cancer is an important cause of
      morbidity and mortality and recommends that New Zealand participate in
      international research in this area.

PMID- 10073157
TI  - Mycobacterial cervical adenitis in Auckland: diagnosis by fine needle aspirate.
AB  - AIMS: To evaluate the role of fine needle aspiration (FNA) in the diagnosis of
      tuberculous and non-tuberculous mycobacterial cervical adenitis in Auckland, and
      to examine the demography of these conditions. METHOD: We reviewed the medical
      records of cases of mycobacterial adenitis in the Auckland region between 1991
      1994. Cases were identified by cross-checking the reference mycobacteriology
      laboratory records, all hospital cytology reports from cases who had an FNA taken
      from the neck region and hospital discharge diagnosis databases. RESULTS: Twenty
      two cases of M tuberculosis adenitis, and 13 of M avium adenitis were identified.
      No FNAs were smear positive for mycobacteria. The FNA from 6/18 (33%) cases of M
      tuberculosis adenitis and from 4/6 (66%) M avium adenitis cases were culture
      positive. Bacteriological confirmation was obtained (by various methods) in 72%
      of tuberculous and in 100% of M avium adenitis cases. The clinical picture was
      different for the two organisms: tuberculous adenitis occurred mainly in
      caucasian adults, while M avium adenitis cases were predominantly caucasian
      children. None of the confirmed cases of tuberculous adenitis demonstrated drug
      resistance to standard anti-tuberculous agents. CONCLUSIONS: (1) Clinicians
      should more consistently include mycobacterial tests when investigating neck
      lumps. (2) FNA is not a reliable diagnostic test for mycobacterial cervical
      adenitis in New Zealand. Here, FNA should only be regarded as a screening test
      for mycobacterial adenitis. If anti-tuberculous treatment is required before it
      is known whether FNA has provided a positive culture, excision biopsy should
      first be performed to identify the mycobacterium and its susceptibility pattern.

PMID- 10073159
TI  - Neonatal abstinence syndrome following abrupt cessation of breastfeeding.
AB  - Neonatal abstinence syndrome is seen commonly in infants born to women on
      methadone maintenance. Many of these infants are breast-fed but few data are
      available on the distribution of methadone in breast milk, particularly for women
      receiving doses greater than 60 mg daily. We report two infants who appeared to
      develop neonatal abstinence syndrome, after abrupt discontinuation of breast
      feeding by women receiving 70 mg and 130 mg of methadone. Women on methadone
      maintenance on high doses should be counselled to wean breast-feeding gradually.

PMID- 10073158
TI  - Road traffic practices among a cohort of young adults in New Zealand.
AB  - AIM: To describe the road safety practices of young adults in New Zealand.
      METHOD: Face to face structured interviews, seeking information on a range of
      road safety practices, were conducted with 948 members of the Dunedin
      Multidisciplinary Health and Development Study cohort when they were 21 years
      old. RESULTS: In the 30 days before the interview, 49% of the males and 32% of
      the females reported driving within two hours of drinking alcohol; 19% males and
      8% females reported driving after drinking too much to perhaps be able to drive
      safely: and 25% males and 9% females reported driving after using marijuana.
      Also, 25% males and 6% females reported that they "often" drove fast just for the
      thrill of it, and 38% males and 11% females reported "often" driving faster than
      120 kph on the open road. Seatbelt use as a driver was reported as "always" or
      "nearly always" by 87% of the males and 95% of the females, but as a rear seat
      passenger it was 34% for males and 47% for females. CONCLUSIONS: Unsafe road
      traffic practices, especially among males, were unacceptably high. Continued
      efforts are required to find new ways of addressing these issues.

PMID- 10073160
TI  - Penicillin- and cephalosporin-resistant pneumococcal meningitis: the future is
      now. The Infection and Immunisation Committee, New Zealand Paediatric Society.

PMID- 10073161
TI  - Adult domiciliary oxygen therapy: position statement of the Thoracic Society of
      Australia and New Zealand.
AB  - Evidence shows that patients with chronic obstructive pulmonary disease and a
      stable daytime PaO2 of 55 mm Hg or less will have longer life expectancy if given
      supplemental oxygen to keep the PaO2 above 60 mm Hg, preferably for longer than
      15 hours a day, including sleep. There is some evidence for improved quality of
      life. It is reasonable to offer this therapy for other lung diseases which cause
      chronic hypoxaemia, and there are also less well defined indications for
      supplemental oxygen during exercise, sleep and air travel.

PMID- 10073162
TI  - The fibromyalgia syndrome: a consensus report.

PMID- 10073163
TI  - Halothane and post-halothane exposure hepatitis.

PMID- 10073164
TI  - Should folate be added to flour?

PMID- 10073165
TI  - Enterohaemorrhagic E coli in Christchurch/South Island not an issue yet.

PMID- 10073166
TI  - [Hepatitis G virus in blood donors].
AB  - PURPOSE: Anti-hepatitis C virus (HCV) antibodies (Abs) screening on blood donors
      has been introduced in France on March 1st, 1990. During the last years, a new
      agent named Hepatitis G Virus (HGV) has been described. We have tested different
      groups of blood donors with the aim of establishing the prevalence of the HGV.
      METHODS: Two hundred and forty-three donors negative for anti-HCV Abs, other
      viral markers and with normal Alanine Amino Transferase (ALT) as control [group
      1], 91 with elevated ALT [group 2], 72 with Abs directed against the hepatitis B
      virus core (Anti-HBc) [group 3], 3 with elevated ALT and anti-HBc Abs [group 4]
      and 70 positive for anti-HCV Abs [group 5] were evaluated. HCV-RNA was tested by
      Polymerase Chain Reaction (PCR) (Amplicor, Roche) and HGV-RNA by in house PCR and
      Abbott Kit. Anti-HGV Abs were tested with Boehringer and/or Abbott tests.
      RESULTS: Among group 1, none subject is found HCV-RNA positive. Seven (2.9%) are
      HGV viremic and 19 positive for anti-HGV Abs (7.8%). Four (4.4%) and 5 (6.9%)
      donors were HGV-RNA positive and 15 (16.5%) and 16 (22.2%) anti-HGV Abs positive
      in group 2 and 3 respectively. In group 4, 2 donors are anti-HGV Abs positive.
      Furthermore, in group 5, 52 subjects (74.3%) are HCV-RNA positive and 9 HGV-RNA
      positive (12.9%). Six donors are viremic for the both viruses. Lastly, 26 donors
      have anti-HGV Abs (37.1%). None subject of the five groups has both HGV-RNA and
      anti-HGV Abs. CONCLUSION: The prevalence of HGV-RNA and anti-HGV is high among
      control donors. In donors with one or two hepatitis surrogate markers (ALT and/or
      anti-HBc Abs), the prevalence of HGV viremia and anti-HGV Abs is increased as
      well as among donors with HCV infection.

PMID- 10073167
TI  - [Tiopronin-induced nephrotic syndrome with minimal glomerular lesions].
AB  - BACKGROUND: In the very large majority of cases, nephrotic syndrome with minimal
      glomerular lesions is an idiopathic condition. Drugs can favor the
      glomerulopathy. The effect of non-steroidal antiinflammatory drugs is well known,
      but other drugs, particularly tiopronin may be incriminated. CASE REPORT: A 73
      year-old patient developed severe nephrotic syndrome with minimal glomerular
      lesions 6 weeks after tiopronin therapy was initiated. Complete and spontaneous
      remission of the nephrotic syndrome was achieved 5 weeks after drug withdrawal.
      No recurrent lipoidic nephrosis has been observed at 3 years follow-up.
      CONCLUSION: Tiopronin-induced nephrotic syndrome with minimal glomerular lesions
      is usually severe and develops rapidly. Remission occurs rapidly after drug
      withdrawal. Weekly urine checks with dip-strips should be proposed in patients
      treated with tiopronin.

PMID- 10073168
TI  - [Association of celiac disease and esophageal small cell carcinoma].
AB  - BACKGROUND: Coeliac disease is known to favor the development of neoplasia.
      Coeliac disease associated with small-cell carcinoma of the esophagus has not
      been reported to date. CASE REPORT: A 51-year-old man with coeliac disease known
      for several years was hospitalized for epigastric pain. Work-up led to the
      diagnosis of small-cell carcinoma of the lower esophagus. The patient was treated
      with 6 cycles of chemotherapy using an etoposide-ciplatinum protocol associated
      with 60 Gy radiotherapy starting at the third cycle. The patient has remained in
      complete remission 2 years after diagnosis. DISCUSSION: Small-cell carcinoma of
      the esophagus is an exceptional finding in a patient with coeliac disease.
      Chemotherapy associated with radiotherapy has been successful in our patient.

PMID- 10073169
TI  - [Paget disease-induced dementia: improvement after tiludronate therapy].

PMID- 10073170
TI  - [A case of typical flushing of atypical origin].

PMID- 10073171
TI  - [Venous thromboembolic diseases in the aged. Survey of patients living in long
      term care facilities].

PMID- 10073172
TI  - [The diabetic patient, the hospital and the general practitioner: a new model for
      community care?].

PMID- 10073173
TI  - [Reanimation of cirrhotic patients: what are the limits].

PMID- 10073174
TI  - [Pancreas transplantation].

PMID- 10073175
TI  - [Classification of dystonias].

PMID- 10073176
TI  - [Genetic dystonia].
AB  - A NEW CLASSIFICATION: The advent of molecular genetics has led to a total
      revision of earlier classifications of primary dystonias. LOCUS DYT-1 PRIMARY
      DYSTONIA: Locus DYT1, situated on chromosome 9, is responsible for the most
      common phenotypic expression of generalized primary dystonia, Ziehen-Oppenheim
      disease. This autosomal dominant disease has variable penetration. It has long
      been recognized that some individuals in families with typical disease only have
      segmentary, multifocal or even focal dystonia. It has been proven by molecular
      genetics that the disease can be expressed simply by familial writers cramp with
      particularly early, and often bilateral, onset. The mutation concerns the torsine
      A gene, whose function remains to be elucidated. Torsine A is found in the
      central nervous system, particularly in the dopaminergic neurons of the locus
      niger. GENERALIZED PRIMARY DYSTONIA UNRELATED TO DYT-1: These dystonias are
      phenotypically different: younger and more variable age at onset, focal
      localization early in the disease course generally involving the cervical or
      cephalic pole, less severe course. Certain forms are linked to chromosome 8
      (locus DYT 6). PRIMARY FOCAL OR SEGMENTARY DYSTONIAS: These primary dystonias
      cause functional or postural disorders and were long considered as sporadic
      despite rare familial cases suggesting a genetic factor. When searched for
      systematically, familial cases are found in 20 to 30% of the cases. The dystonia
      is transmitted by dominant autosomal heredity with reduced penetration.
      Phenotypically, expression is heterogeneous with a constant frequency of
      unrecognized or neglected forms and of postural forms. One form is known to be
      linked to chromosome 18 (locus DYT 7). DOPA-RESPONSIVE DYSTONIA: This class
      represents 5 to 10% of childhood dystonias. The phenotypic expression is
      polymorphous but symptoms always improve with very small doses of L-dopa. Both
      sporadic, and more frequently familial, cases are described. Some forms are
      recessive, caused by mutation of the gene coding for tyrosine hydroxylase, others
      are autosomal dominant, often linked to mutation of the gene coding for GTP
      cyclohydrolase. RAPID ONSET DYSTONIA SYNDROME-PARKINSONISM: This dominant
      autosomal dystonia is quite exceptional, ... and intriguing.

PMID- 10073177
TI  - [Secondary dystonias. Clinical analysis and diagnostic approach].
AB  - DEFINITIONS: Dystonia is a muscle contraction disorder marked by sustained
      involuntary clonic contortions or abnormal posture. Primary dystonias can be
      divided into familial forms related to genetic anomalies and idiopathic forms.
      Secondary dystonias are related to an underlying neurological disease. METABOLIC
      DISEASES: Secondary dystonias related to metabolic diseases generally occur early
      before puberty although late onset forms have been described. Other signs, in
      association with the dystonia, include mental retardation, epilepsy, cerebellous
      or pyramidal signs, oculomotor disorders, or a neuropathy. Occasionally,
      extraneurological signs suggest the diagnosis. Biological markers are known for
      most of these dystonias. EVENT-RELATED DISEASES: In some cases, the dystonia is
      the only sign and develops as a sequela to an earlier neurological event such as
      neonatal anoxia, trauma, vascular event or adverse effect of neuroleptics. HEMI
      DYSTONIAS: Dystonias limited to one side are generally secondary.

PMID- 10073178
TI  - [Treatment of dystonias].
AB  - SYMPTOMATIC TREATMENT: Treatment of idiopathic dystonia depends on the age of
      onset and the extent of the disease. Symptomatic treatment has made many advances
      over the last 20 years. CHILDHOOD ONSET GENERALIZED DYSTONIA: In childhood onset
      cases, it is important first to exclude dopa-responsive dystonia. Most of these
      patients will respond subsequently to high dose anticholinergics. ADULT ONSET
      FOCAL DYSTONIA: Treatment of this form has been transformed by botulinum toxin
      therapy. TREATMENT: The treatment of each focal dystonia (blepharospasm,
      spasmodic torticollis, oromandibular dystonia, laryngeal dystonia, writer's
      cramp, foot dystonia and axial dystonia) are reviewed. Treatments must be
      titrated carefully. Botulinum toxin injections require precision and must be
      repeated regularly. A rehabilitation program must be adapted to each individual.
      Surgery, in very severe cases, requires an extensive well-planned discussion of
      indications.

PMID- 10073179
TI  - Management of portal hypertension-related bleeding.
AB  - Although endoscopic sclerotherapy and TIPS remain the primary therapeutic tools
      in management of acute variceal bleeding, surgical shunts must be considered for
      low-risk patients with bleeding. OLTx is the only definitive treatment for
      patients with end-stage liver disease and vascular decompensation. Furthermore,
      the current prospective multicenter randomized study, funded by the National
      Institutes of Health and Human Services, will help determine the role of DSRS
      versus TIPS in cirrhotic patients with good hepatic reserve. This is a necessity
      in a time in which organ shortages are ever-increasing because of a growing
      disparity between the number of patients listed for transplantation each year
      versus the number of suitable organ donors. The various surgical techniques
      should be applied in different situations based on patients' clinical status at
      the time of the bleed and whether they are considered candidates for liver
      transplantation.

PMID- 10073180
TI  - The hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome is a disease entity seen in association with liver
      failure and other disease entities. It is a devastating consequence of liver
      failure that results in a significant morbidity for affected patients. Currently,
      there are no identified medications that ameliorate the symptoms of hypoxemia in
      this disease state. Recent research, however, has begun to unravel the
      pathobiology of the vascular dilations that arise in the lungs of patients with
      liver failure. In this article, a compendium of current knowledge is presented,
      as well as the contemporary methods for identifying and treating patients.

PMID- 10073181
TI  - Hepatobiliary malignancies. Primary hepatic malignant neoplasms.
AB  - Primary hepatic tumors are epithelial, mesenchymal, or mixed in origin. Of these,
      epithelial tumors are the most common and include hepatocellular carcinoma,
      cholangiocarcinoma, mixed hepatocholangiocarcinoma, hepatoblastoma, and a variety
      of more rare tumors. Hepatocellular carcinoma, also know as hepatoma or malignant
      hepatoma, is the most common, followed by cholangiocarcinoma. This article
      discusses these two malignancies.

PMID- 10073182
TI  - Immunosuppressive therapy.
AB  - Although several new immunosuppressive medications have been developed in the
      past decade, many possible avenues are yet to be explored. Although the newer
      agents have not reflected any clear benefit in patient or graft survival over CsA
      or tacrolimus, they have been useful in reducing the incidence and severity of
      rejection, reducing the concomitant use of steroids, and decreasing the doses of
      CsA or tacrolimus to minimize their toxicity profile. The appearance of these new
      agents has given more options to clinicians, who can select the one with the
      least toxicity and most efficacy for individual patients. In the future,
      combinations of these agents, in conjunction with a strategy to induce tolerance
      of the donor organ without drug toxicity, will be the goal.

PMID- 10073183
TI  - Fulminant hepatic failure.
AB  - Fulminant hepatic failure is a disease of varied causes and a high mortality
      rate. A sudden onset, jaundice, hepatic encephalopathy, and multiorgan failure
      are the hallmarks of this syndrome. The management of patients with FHF requires
      a multidisciplinary approach and intense monitoring. The availability of liver
      transplantation has provided the means to rescue such patients from near-certain
      death. Early prognostication and timely availability of donor livers are
      requirements for a successful outcome. The development of effective artificial
      liver support devices may greatly prolong the window of opportunity to provide a
      donor liver, or alternatively, to allow the native liver to regenerate.

PMID- 10073184
TI  - Early complications after orthotopic liver transplantation.
AB  - The cost and impact of early post-transplant complications continue to be high.
      Diagnosis and management involves a high index of suspicion, rapid diagnostic and
      therapeutic interventions, and elimination of technical problems. Preoperative
      assessment of the donor and recipient medical condition and meticulous attention
      to detail during the technical performance of OLTx are the mainstays in achieving
      a good outcome.

PMID- 10073185
TI  - Liver transplantation for chronic viral hepatitis.
AB  - A better understanding of the mechanism of viral replication and of viral
      transmission has led to improved results with OLTx for patients with end-stage
      liver disease caused by viral hepatitis. Patients with hepatitis-B-related liver
      disease who are HBV-DNA negative can expect excellent survival after OLTx with
      long-term HBIG therapy. Patients coinfected with HDV who are HBV-DNA negative can
      also expect an excellent rate of survival. HBV-DNA-positive patients may benefit
      from the addition of lamivudine to the prophylactic regimen both before and after
      OLTx. De novo HBV infections generally have a very benign course. Lamivudine has
      proven to be very effective in the treatment of both de novo and recurrent HBV
      infection after OLTx; however, resistance can develop. Allografts from donors
      with antibodies to HBV can be used most effectively when directed to recipients
      who also harbor HBV antibodies. The recurrence of HCV infection after OLTx is
      universal; however, the 5-year survival rate in patients who received OLTx for
      HCV-related liver disease is not diminished. Although a few patients experience
      an aggressive recurrence of HCV infection after OLTx, prognostic indicators have
      not been determined to allow for identification of these patients. Alpha
      interferon does not seem to be effective in the treatment of recurrent HCV
      infection after OLTx. Trials with combination alpha-interferon-ribavirin are
      underway. Retransplantation for HCV-related allograft failure can be performed
      safely in patients if performed before the onset of other organ system failure.
      Finally, anti-HCV-positive recipients of allografts from anti-HCV-positive donors
      have an excellent 5-year survival rate.

PMID- 10073186
TI  - Autoimmune liver diseases. Recurrence after liver transplantation.
AB  - PBC and AIH recur after OLTx. The recurrence of PSC is less clear. Recurrence of
      these diseases seems to be of relatively little importance in the short term;
      however, longer follow-up is required to address the significance of recurrent
      disease. Immunosuppression in these patients may alter the natural history of
      these entities in the post-transplant setting.

PMID- 10073187
TI  - Liver transplantation for metabolic liver diseases.
AB  - Liver transplantation has revolutionized the outcome of metabolic liver diseases
      that are caused by defects in hepatocytes (e.g., Wilson's disease) or by
      excessive deposition of substrates secondary to their increased absorption (e.g.,
      hemochromatosis). Early diagnosis and referral are the keys to successful
      outcome. The timing of liver transplantation for patients on medical therapy
      depends on a lack of biochemical and clinical evidence of improvement. Overall
      outcome following liver transplantation depends on the severity of multisystem
      involvement and preoperative decompensation.

PMID- 10073188
TI  - Pediatric transplantation.
AB  - Advances in organ preservation, surgical technique, and postoperative care have
      permitted the rapid development of liver transplantation in children.
      Consequently, the applicability of this procedure has gone beyond the treatment
      of life-threatening complications of chronic liver disease and now includes
      disabling morbidities and quality-of-life issues. The use of hepatic segments for
      transplantation with reduced or split cadaveric grafts and living-related donors
      has decreased the mortality of children awaiting liver transplantation. We are
      presently armed with a new potent immunosuppressive drug, tacrolimus, and an
      understanding that the migration and grafting of passenger leukocytes of bone
      marrow origin is the seminal explanation for allograft acceptance. The next
      forefront will involve manipulation of the process not only for the
      transplantation of already successful whole organs--such as the liver, kidney,
      pancreas, and heart--but also in the development of the intestinal
      transplantation program. Thus, augmentation of leukocyte traffic in unconditioned
      recipients of cadaver allografts with concomitant intravenous infusion of donor
      bone marrow cells under the same immunosuppressive management of tacrolimus
      prednisone treatment will be the path into the future.

PMID- 10073190
TI  - Primary care use by specialty clinic patients at a county hospital.

PMID- 10073189
TI  - Chimerism and xenotransplantation. New concepts.
AB  - In both transplant and infectious circumstances, the immune response is governed
      by migration and localization of the antigen. If the antigenic epitopes of
      transgenic xenografts are sufficiently altered to avoid evoking the destructive
      force of innate immunity, the mechanisms of engraftment should be the same as
      those that permit the chimerism-dependent immunologic confrontation and
      resolution that is the basis of allograft acceptance. In addition to "humanizing"
      the epitopes, one of the unanswered questions is whether the species restriction
      of complement described in 1994 by Valdivia and colleagues also necessitates the
      introduction of human complement regulatory genes in animal donors. Because the
      liver is the principal or sole source of most complement components, the
      complement quickly is transformed to that of the donor after hepatic
      transplantation. Thus, the need for complementary regulatory transgenes may vary
      according to the kind of xenograft used. Much evidence shows that physiologically
      important peptides produced by xenografts (e.g., insulin, clotting factors, and
      enzymes) are incorporated into the metabolic machinery of the recipient body. To
      the extent that this is not true, xenotransplantation could result in the
      production of diseases that are analogous to inborn errors of metabolism. In the
      climate of pessimism that followed the failures of baboon to human liver
      xenotransplantation in 1992-1993, it seemed inconceivable that the use of even
      more discordant donors, such as the pig, could ever be seriously entertained;
      however, this preceded insight into the xenogeneic and allogeneic barriers that
      has brought transplantation infectious immunity to common ground. With this new
      insight and the increasing ease of producing transgenic donors, the goal of
      clinical xenotransplantation may not be so distant.

PMID- 10073191
TI  - Improving prenatal care services for low-income African American women and
      infants.
AB  - Increasing the level of prenatal care among African American women may be one
      method of improving the health and well-being of African American women and
      children. This article identifies factors influencing access to and use of
      prenatal care and strategies for increasing the use of prenatal care among low
      income African American women. Barriers to prenatal care, the strengths and
      limitations of prenatal care in reducing infant mortality and improving infant
      outcomes, and the importance of providing more comprehensive prenatal care that
      addresses both the medical and psychosocial needs of the low-income African
      American mother and her infant are discussed. Changes in prenatal care services
      that include the medical and lay communities, public health organizations, public
      policy organizations, and medical financing institutions are identified.

PMID- 10073192
TI  - Implementing breast and cervical cancer prevention programs among the Houma
      Indians of southern Louisiana: cultural and ethical considerations.
AB  - This paper provides an overview of the ethical and cultural issues that were
      taken into account in planning a cross-cultural study of barriers to breast and
      cervical cancer screening among Houma Indian women who reside in Terrebonne
      Parish, Louisiana. In such cross-cultural studies, the investigators and members
      of the target population are from different cultural backgrounds. In planning the
      study, ethical principles and cultural norms were carefully specified to ensure
      that the welfare of the participants would be protected and potential benefits
      maximized. This experience with the Houma Indian Nation illustrates the need for
      greater participation of research subjects in the planning and implementation of
      studies on their behalf. An ethical, culturally sensitive approach to cancer
      control research is needed to address the health concerns of Native American
      populations.

PMID- 10073193
TI  - Exploratory analysis of factors associated with teens' repeated childbearing.
AB  - This study was designed to explore the factors regarding unique determinants of
      repeat childbearing among teens. The influence that key people have on subsequent
      teen childbearing is examined. Data for this research were gathered in focus
      groups with teen mothers and parents of teen mothers who access the Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) in Georgia. Based on the
      results, repeated childbearing appears to occur within the context of poor parent
      child relations, conflicting support for the roles teen mothers are expected to
      assume, limited social pressures for effective fathering, and limited access to
      social services for all family members. Pregnancy prevention efforts by agencies
      for teen mothers should coordinate services for the teen mother, her parent, and
      her partner.

PMID- 10073194
TI  - Hypertension in community-dwelling elders from a statewide study: implications
      for nonpharmacologic therapy.
AB  - This study used multivariate analysis to determine the sociodemographic variables
      that predict whether hypertensive elders who are aware of their disease
      deliberately make lifestyle modifications aimed at controlling their
      hypertension. The data are from the 1990 Panel Study of Older South Carolinians
      (n = 6,473). The researchers performed five separate logistic regressions, each
      to predict the odds that the elders made specific lifestyle changes to reduce
      their hypertension. The dependent variable in the first regression was 1 = quite
      smoking to reduce hypertension and 0 = did not quite smoking to reduce
      hypertension. Changing diet, exercising, taking medication, and using stress
      management techniques were the dependent variables in the second, third, fourth,
      and fifth regressions, respectively. Significant determinants included age,
      gender, marital status, socioeconomic status, previous medical history, and
      social participation. This paper discussed implications for prevention programs.

PMID- 10073195
TI  - Predictors of cervical cancer screening in Mexican American women of reproductive
      age.
AB  - Several barriers impede cancer prevention in the Mexican American population.
      This study identified sociocultural factors that could be used to increase
      screening rates for cervical cancer in women of reproductive age. A survey was
      conducted in 1991 of 366 Mexican American women ages 18 to 40 in Tucson, Arizona,
      to assess current compliance with cervical cancer screening guidelines and
      several psychological, social, and cultural variables. Women who had never been
      screened (13 percent of the sample) had a knowledge deficit, no gynecological
      care, and no sexual activity. Women not screened annually (16 percent) lacked
      preventive care, imperfectly understood the Pap test, had lower self-efficacy
      expectations for understanding physicians, experienced higher emotional stress
      about the test, and were older and less acculturated. Women who have never been
      screened require basic education on cancer and cancer screening and policy
      changes increasing access to care. For women with less routine screening,
      preventive care, supportive attitudes, and health care skills must be encouraged.

PMID- 10073196
TI  - Medical education in underserved communities: experience from an urban area
      health education center.

PMID- 10073197
TI  - Cultural humility versus cultural competence: a critical distinction in defining
      physician training outcomes in multicultural education.
AB  - Researchers and program developers in medical education presently face the
      challenge of implementing and evaluating curricula that teach medical students
      and house staff how to effectively and respectfully deliver health care to the
      increasingly diverse populations of the United States. Inherent in this challenge
      is clearly defining educational and training outcomes consistent with this
      imperative. The traditional notion of competence in clinical training as a
      detached mastery of a theoretically finite body of knowledge may not be
      appropriate for this area of physician education. Cultural humility is proposed
      as a more suitable goal in multicultural medical education. Cultural humility
      incorporates a lifelong commitment to self-evaluation and self-critique, to
      redressing the power imbalances in the patient-physician dynamic, and to
      developing mutually beneficial and nonpaternalistic clinical and advocacy
      partnerships with communities on behalf of individuals and defined populations.

PMID- 10073198
TI  - Changes in usual sources of medical care between 1987 and 1992.
AB  - This study is a secondary analysis of data from the 1987 and 1992 National Health
      Interview Surveys. Analyses compared adults who do not have a usual source of
      care and those who identified usual sources of care in 1987 and 1992. Between
      these years, the estimated number of adult Americans without a usual source of
      care rose from 29.7 to 39.4 million. Adults were 0.75 times less likely to
      identify a physician's office and 1.8 times more likely to identify an outpatient
      clinic as that source of care in 1992 than they were in 1987. These changes were
      observed among Americans of all demographic and socioeconomic backgrounds.
      Increasing numbers of adult Americans without a usual source of care and shifts
      in care from physicians' offices to outpatient clinics may reflect deteriorating
      access to care. This may affect quality and costs of medical care, demanding
      continued surveillance of sources and access to care.

PMID- 10073199
TI  - Health status, needs, and health care barriers among the homeless.
AB  - Perceived health status, health conditions, and access and barriers to care are
      important predictors of mortality and the use of services among the homeless.
      This study assesses these issues by structured interview of 128 homeless adults
      from San Francisco. Of these adults, 21.1 percent were women (mean age 37
      compared to 42 for men). In terms of ethnicity, 38 percent were white; 30 percent
      were African American; 17 percent were Latino; and 15 percent were Asian/Pacific
      Islander, Native American/Alaskan, or of mixed ethnicity. Of these adults, 49
      percent rated health as poor or fair. Men were four times as likely as women to
      report their health status as excellent or good. Persons of color were more
      likely to report unmet needs for shelter, regular meals, employment, and job
      skills/training. These findings add information on those homeless not often
      included in research and indicate that these marginalized individuals may be in
      the poorest health.

PMID- 10073200
TI  - Visits to specialists under Medicare: socioeconomic advantage and access to care.
AB  - This study examines the relationship between socioeconomic advantage and the
      likelihood of receiving specialty care in a nationally representative sample of
      older Americans participating in fee-for-service Medicare. In 1992, 62.9 percent
      of Americans aged 65 and older visited a specialist physician at least once.
      Being white, having more education, and having a higher income were each
      independently associated with a higher likelihood of visiting a specialist.
      Having insurance to supplement basic Medicare coverage was also independently
      associated with an increased likelihood of visiting a specialist; disadvantaged
      elders are less likely to have such supplemental insurance. Therefore, based both
      upon socioeconomic disadvantage and a lack of insurance to supplement the basic
      Medicare benefit, black, less educated and low-income elders are less likely to
      receive specialty services under fee-for-service Medicare. As the program
      evolves, it will be important to continue to monitor access to specialty care in
      vulnerable, socioeconomically disadvantaged populations.

PMID- 10073201
TI  - Access to primary care for patients with diabetes at an urban public hospital
      walk-in clinic.
AB  - The purpose of this study was to determine the regular source of primary care,
      the content of care, and barriers to accessing primary care for 218 medically
      indigent adults with diabetes mellitus. Patients were surveyed at a public
      hospital walk-in clinic and were queried regarding demographics, regular source
      of care, and the content of care they received during the preceding year. Seventy
      percent of the patients were medically uninsured, and 60 percent had household
      incomes under $10,001. Forty-three percent reported no regular source of care,
      and 18 percent named an episodic care site as their regular source. Patients with
      a regular source of primary care had twice as many annual ambulatory visits as
      those without primary care. Patients with a regular source of primary care
      reported more diabetic-related services than those without. This patient
      population is largely poor and uninsured and has difficulty accessing primary
      care.

PMID- 10073202
TI  - Does race influence the provision of care to persons with sickle cell disease?
      Perceptions of multidisciplinary providers.
AB  - This study examined whether multidisciplinary health care providers (HCPs)
      perceived race of persons with sickle cell disease (SCD) as an influence in the
      delivery of health care. A total of 227 multidisciplinary HCPs completed the
      three-item Influence of Patient Race on Provision of Health Care Services Index
      (Cronbach's alpha = 0.77). Results suggest that African American HCPs were more
      likely to perceive race as an influence along all scale items, whereas Caucasian
      and other race HCPs did not. Female HCPs and those who serve adults were more
      likely than male HCPs and those who serve children to perceive race as having an
      influence on the quality of health care. Findings suggest a need for the
      examination of the health care delivery systems in which persons with SCD receive
      care to determine if race does, in fact, affect the delivery of health care and
      to explain the discrepancies in the perceptions of the HCPs.

PMID- 10073203
TI  - Reaping the fruits of research: promoting health equity for all.

PMID- 10073204
TI  - Slipping through the safety net: implications for women's health.
AB  - The failure of the 104th Congress to pass legislation that would have provided
      universal health care coverage has created gaping holes in the health care safety
      net for the working poor. As a result, the number of Americans without health
      insurance, which was 37 million in 1992, could reach 50 million in 1998. Current
      changes in welfare policy, centered on reform of the joint federal-state program
      Aid to Families with Dependent Children (AFDC), have further redefined the safety
      net for the poor. These changes may jeopardize the health of poor women as any
      change in eligibility requirements for AFDC also limits eligibility for Medicaid.
      Given the financial and social difficulties facing poor women, a growing number
      of researchers are redefining what constitutes research on women's health.
      Research is needed on how the high rates of health problems and few health
      resources of poor racial/ethnic minority women affect their quality of life.

PMID- 10073205
TI  - Personal costs associated with high-risk prenatal care attendance.
AB  - Personal costs associated with attending prenatal care may influence women's care
      seeking behavior, particularly poor, pregnant women and those with complicated
      pregnancies who receive more visits. This study described personal costs incurred
      by poor, high-risk pregnant women while attending care. Personal costs included
      direct out-of-pocket and time costs. Also, the relationship between personal
      costs and attendance was examined. Mean direct costs throughout pregnancy were
      $101.96 per patient. Women waited a mean of 3.22 hours per visit for care and
      received direct physician care for a mean of 5 minutes. As child care costs
      increased, attendance decreased significantly (r = 0.60, p < or = 0.05). As
      transportation costs, meal costs, wages lost, and time spent awaiting care
      increased, attendance decreased. Prenatal care has associated dollar and time
      costs for patients. Problem solving these issues with patients is critical.
      System changes to decrease waiting times and to address child care issues are
      needed.

PMID- 10073206
TI  - African American women and diabetes: a sociocultural context.
AB  - Diabetes is the fourth leading cause of death among African American women. One
      in four black women (23.4 percent) older than age 55 has diabetes. In evaluating
      the experience of black women with diabetes, an understanding of their social
      context is essential. Resulting from historical and sociocultural factors, black
      women have relatively lower income and education levels and consequently, poorer
      health and restricted access to quality health care. In a sense, being black,
      female, elderly, and chronically ill places this group in quadruple jeopardy.
      Tackling the problem of diabetes among African American women is a public health
      priority and requires a multilevel approach.

PMID- 10073207
TI  - Severity of spousal and intimate partner abuse to pregnant Hispanic women.
AB  - Abuse to pregnant women can result in complications to maternal and child health.
      This study assessed the severity of intimate male partner abuse to Hispanic
      pregnant women receiving prenatal care at an urban public health department. The
      mean age of the 329 pregnant, abused Hispanic women was 24 years. The women had
      an average of eight years of education, annual incomes of less than $10,000, and
      most spoke only Spanish. In all, 30 percent of the women had been threatened with
      death, 18 percent had been threatened with a knife or gun, 80 percent had been
      shaken or roughly handled, 71 percent pushed or shoved, and 64 percent slapped on
      the face and head. Pregnant, abused Hispanic women experience abuse of sufficient
      severity to pose a risk to maternal and child health. Prenatal care provides a
      window of opportunity for routine abuse assessment and counseling for low-income,
      Hispanic pregnant women.

PMID- 10073208
TI  - Beliefs concerning contraceptive acquisition and use among low-income women.
AB  - Despite the availability of a wide variety of safe and effective contraceptives,
      unintended pregnancy remains a problem of considerable social and public health
      concern. This qualitative, descriptive investigation was based on Ajzen's Theory
      of Planned Behavior. The study examined attitudinal and normative beliefs, as
      well as perceived control factors that may affect a woman's intention to acquire
      and use specific contraceptive methods. The study sample consisted of 42 low
      income women of reproductive potential. In face-to-face, audiotaped interviews,
      open-ended questions were used to elicit salient beliefs that affected these
      women's decision making about contraceptive acquisition and use. Respondents
      named embarrassment as a factor influencing condom acquisition and use; concerns
      about potential risks and side effects were a major deterrent to use of hormonal
      contraceptives. Implications for practitioners and public policy are suggested.

PMID- 10073209
TI  - Cancer screening in homeless women: attitudes and behaviors.
AB  - Little is known about the use of cancer-screening services in homeless women and
      their attitudes about early detection programs. Face-to-face interviews were
      conducted with homeless women in San Francisco to determine rates of clinical
      breast exams, mammograms, and Pap smears. A total of 105 women were randomly
      selected from two homeless shelters. By self-report, 51 percent were current on
      clinical breast exams, 47 percent on mammograms, and 54 percent on Pap smears.
      These women had very positive attitudes toward receiving cancer-screening exams.
      In multivariate analyses, discussion about cancer prevention with a health care
      provider predicted current clinical breast exams and mammograms. More medical
      visits predicted being current on mammograms and Pap smears. Although homeless
      women represent a unique group of the urban poor, they are accessing cancer
      screening exams at rates comparable to the general population.

PMID- 10073210
TI  - Preventive health counseling reported by uninsured women with limited access to
      care.
AB  - Low-income women in the childbearing years are at an increasing risk of becoming
      uninsured as welfare reforms are enacted and women enter minimum-wage jobs
      without insurance benefits. This study contrasts preventive counseling reported
      by low-income uninsured mothers and mothers insured through Medicaid. Low-income
      women attending Women, Infant, and Children (WIC) clinics and human services
      offices who had received health care during the previous 12 months (N = 406) were
      asked if they had received counseling from a health provider regarding any of
      seven types of preventive health behaviors. Uninsured women were less than half
      as likely to receive counseling on three or more preventive topics (OR = 0.42) as
      were mothers on Medicaid. Risk estimates were stable on bivariate analyses and
      logistic regression models. Findings indicate that opportunities for preventive
      health counseling need to be maximized for this group already experiencing
      compromised access to care.

PMID- 10073211
TI  - A trial to increase mammography utilization among Los Angeles Hispanic women.
AB  - The objective of this program was to increase mammography screening rates among
      Hispanic women through a series of targeted community-wide interventions. A
      diverse array of outreach efforts was offered by the program to increase
      awareness and use of screening mammography. Before the program, 12 percent of the
      Hispanic women surveyed in the intervention community had been screened, compared
      with 27 percent after the program. There was no change in screening among
      Hispanic women in the control community (23 percent before and 24 percent after
      the program). The program demonstrated that the awareness and behavior of "hard
      to-reach" underscreened Hispanic women can be changed through intensive targeted
      outreach and that a church-based cancer control program can play an effective
      role in the process. This finding has national health policy implications.

PMID- 10073212
TI  - Peer counseling in a culturally specific adolescent pregnancy prevention program.
AB  - This study evaluated the effects of peer counseling in a culturally specific
      adolescent pregnancy prevention program for African American females. A random
      pretest and multiple posttest experimental and comparison group design was used
      to obtain data on a sample of 63 female African American adolescents, ages 12 to
      16, who lived in four public housing developments. Descriptive data and tests of
      significance revealed that none of the participants who received peer counseling
      became pregnant within three months of the intervention. Findings revealed a
      statistically significant increase in reproductive and other self-related
      knowledge topics among the experimental group when comparing pretest and eight
      week posttest scores. Most participants had not had sexual intercourse; the
      average age of sexual onset was 12 years in the experimental group and 11 years
      in the controls. Designing and implementing culturally specific adolescent
      pregnancy prevention programs for adolescents younger than age 11 and/or before
      sexually active seems appropriate.

PMID- 10073213
TI  - A survey of African Americans at a community health fair.

PMID- 10073214
TI  - Preparing for managed care: family practice residents and capitated care in
      community health centers.
AB  - This article examines the financial impact on patients of family practice
      residents when a community health center (CHC) serving as a residency training
      site is converted to a capitated payment system. The costs in this analysis
      included using and educating family practice residents at CHCs, the cost of
      patient encounters at CHCs, and the cost of contracted capitated services. These
      costs were measured against capitated per member per month (pmpm) payments
      received by the CHC. If capitated patients were cared for by residents, the CHC
      would lose $8.42 pmpm. The CHC faced a $5.98 pmpm loss if it used staff
      physicians rather than residents. This analysis suggests there are educational
      costs associated with training physicians in capitated health care delivery
      systems. Family practice residencies and CHCs must prepare for the conversion to
      capitated systems; academic centers with managed care contracts must control
      patient encounter costs and utilization to remain competitive.

PMID- 10073215
TI  - Iron deficiency and maternal feeding practices among high-risk urban children.
AB  - This study evaluated the nutritional knowledge and feeding practices (via a
      verbal questionnaires) of the clients of one semiurban women, infants, and
      children (WIC) center, which serves exclusively younger women (aged 12-21) and
      their children, and compared these variables to the hemoglobin levels of their
      infants and children. No significant benefit from documented WIC education
      regarding iron was detectable. African American identification was associated
      with childhood anemia (p = 0.05); the presence of concurrent medical problems
      approached significance (p = 0.06). Other previously reported risk associations
      were not found to be significant. Children with low iron ate more meals outside
      the home per week (2.9 vs. 1.9, p = 0.10). Despite the proven value of the WIC
      program in reducing childhood iron deficiency, it appears that members of certain
      very high-risk populations may not experience the full benefit of this
      nutritional program and may require additional, targeted interventions.

PMID- 10073216
TI  - Psychosocial factors and birth outcome: African American women in case
      management.
AB  - The relationship between psychosocial risk factors and birth outcomes among
      African American pregnant women is explored. The study focuses on
      social/environmental stressors and proposes a workable model for delivery of
      services based on case management principles. Unstable income, perinatal medical
      problems, alcohol use, smoking, access to prenatal care, internal barriers to
      care, compliance problems, negative experiences with providers, depression,
      unresolved grief, and fetal substance exposure were significantly associated with
      low birthweight. Unstable income, compliance problems, internal barriers to care,
      and poor access to care were significantly associated with preterm delivery.
      Specific interventions aimed at providing social support, facilitating access to
      care, health education, and encouragement to verbalize feelings about problems
      were significantly associated with the number of problems that the client was
      able to solve. The data indicated the importance of psychosocial, environmental
      and medical risk factors in the prediction of low birthweight and preterm
      delivery in a high-risk population.

PMID- 10073217
TI  - Relationships between socioeconomic status and race-specific cervical cancer
      incidence in the United States, 1973-1992.
AB  - The association between low socioeconomic status (SES) in minority groups and
      higher incidence and mortality from cervical cancer was examined using two large
      U.S. databases. With cases from 1973 to 1992, all registries of the Surveillance,
      Epidemiology, and End Results (SEER) (except Hawaii) were used to calculate
      incidence rates of in situ and invasive cervical cancers by race group. SES
      indicators were derived from the Regional Economic Information System, Department
      of Commerce. Higher levels of SES indicators were related to decreased risk and
      lower incidence of invasive cancers in all race groups, but especially white and
      black populations, and to increased incidence of situ cancer in these
      populations. Results suggest that higher SES status is related to a decrease in
      invasive cervical cancer, but an increase in in situ cervical cancer in recent
      years. These findings may explain the racial differences in cervical cancer
      incidence and help target intervention programs.

PMID- 10073218
TI  - Medicaid beneficiaries' experiences in HMO and fee-for-service health care.
AB  - How do HMO-enrolled Medicaid beneficiaries' ratings of access to, and
      satisfaction with, their health care compare with the ratings of those
      beneficiaries receiving care in fee-for-service settings? Do poor single mothers
      report differences in access to, and satisfaction with, their HMO health care
      compared with those living in other family structures? These questions were
      examined with survey data from 961 California Medicaid recipients in 1991.
      Medicaid recipients enrolled in HMOs reported more difficulty gaining access to,
      and less satisfaction with, various aspects of the health care system. HMO
      enrolled single mothers reported particularly negative experiences with their
      health care. The findings suggest a potential lack of fit between the health
      needs of the poor and the aims of managed health care.

PMID- 10073219
TI  - Some results of 50 years of research on the resistance to plum pox virus.
AB  - Over 300 references on the resistance of stone fruit species to plum pox virus
      (PPV) have been utilized for the summarization of relevant information in this
      review. Methods of testing PPV resistance, procedures of evaluation and
      characterization of PPV resistance as well as breeding of PPV-resistant cultivars
      are briefly discussed. Altogether 370 cultivars, hybrids and clones of plum,
      peach, apricot, nectarine and wild Prunus species are tabulated together with the
      authors who have reported on their immunity, resistance and tolerance.

PMID- 10073220
TI  - Relationship between concentration of plum pox virus and content of pigments in
      virus-infected symptomatic apricot leaves.
AB  - Besides other factors, occurrence of plum pox virus (PPV)-caused spots and mosaic
      symptoms on leaves of stone fruits are known to influence important physiological
      functions including production of assimilates. Apricot (Prunus armeniaca L.)
      seedlings were used as a test material for typical manifestation of symptoms of
      the disease on the foliage. The relations of the abovementioned visual symptoms
      to the virus and pigments concentrations in leaves have so far not been known
      sufficiently. We detected PPV only in symptomatic leaf tissue of the infected
      apricot. In the green tissue of the same leaves, the double-antibody sandwich
      enzyme-linked immunosorbent assay (DAS-ELISA) of the virus was negative. The
      content of pigments was changed by PPV infection. In the symptomatic leaf
      tissues, the content of chlorophylls "a" and "b" was lower, and the content of
      carotenoids was higher in comparison to the respective controls. We conclude that
      the PPV infection could cause the change in the content of particular leaf
      pigments leading to the decreased yield of photosynthesis which in turn could
      influence the sugar metabolism in the infected trees.

PMID- 10073221
TI  - Comparison of different methods of RNA isolation for plum pox virus detection by
      reverse transcription-polymerase chain reaction.
AB  - The diagnosis of plum pox virus (PPV) is still considered one of the most
      important aspects of the "sharka" problem. In fact, different studies
      demonstrated an uneven distribution of the virus in infected trees due to a high
      variability in virus concentration. These aspects complicate the PPV diagnosis.
      To date, biological, serological and molecular assays have been successively
      developed in order to obtain sensitive and efficient PPV detection techniques. In
      particular, the polymerase chain reaction (PCR) technique seems to be promising
      and can be considered the most sensitive and reliable one. Preparation of viral
      RNA is still a fundamental step in reverse transcription-PCR (RT-PCR) technique,
      especially when applied to large scale testing, i.e., for certification purposes.
      In order to find the most rapid and efficient procedure, we have compared three
      different procedures of extraction of viral RNA to be processed RT-PCR. Their
      common characteristics is their capacity to extract the RNA from a small amount
      of plant tissue without organic solvents in the extraction fluid. The procedures
      were as follows: an immuno-capture (IC) method using a specific antiserum, a
      silica-capture (SC) method using a non-specific matrix, and a simple and rapid
      RNA extraction (RE) method. They all were followed by one-tube RT-PCR. The
      obtained results show that all the three techniques allowed a successful
      amplification and detection of PPV in tested samples except the SC-PCR method
      which proved less effective. In fact, the IC-PCR and RE-PCR methods amplified and
      detected PPV in all isolates tested, while the SC-PCR method was able to reveal
      the presence of the virus in apricot and infected control samples only.

PMID- 10073222
TI  - Investigation on the plum pox virus resistance in different apricot genotypes.
AB  - In our three-year investigation, 164 apricot trees of different old German
      varieties cultivated in the Mansfelder Land region were tested for the plum pox
      virus (PPV) resistance by double grafting in greenhouse conditions using an
      isolate of PPV D strain from our region. We selected 25 genotypes with
      quantitative resistance and two with immunity. The first results of field trials
      are comparable with those from greenhouse. With cvs. Virosia and Brevira, two
      local quantitatively resistant varieties will be available from autumn 1998. The
      origin of both trees, which were found to be immune, is still unclear. They will
      be used for propagation only after the variety identification.

PMID- 10073224
TI  - Breeding of plums and prunes resistant to plum pox virus.
AB  - At Hohenheim we started a plum breeding programme to get new sharka-resistant
      cultivars with better fruit quality. In the last years we have recognized that
      the resistance of all cultivated plums is based on quantitative criteria and
      therefore relative. For this reason we changed our strategy for the resistance
      breeding. For the first breeding cycle we used special donors with quantitative
      resistance. Today, the qualitative resistance is more integrated. We intend to
      combine both types of resistance in the hexaploid genome of Prunus domestica to
      obtain an absolute and durable resistance. To achieve this aim, we have to
      consider the evaluation of resistance, the genetic resources, the inheritance of
      the resistance and also the breeding methods. The results of our resistance
      breeding study are presented.

PMID- 10073223
TI  - Characterization of plum pox virus isolates from Slovakia.
AB  - Plum pox virus (PPV) isolates from stone-fruit trees (plums, myrobalans, apricots
      and peaches) from orchards and gardens were characterized. To characterize their
      biological properties, several PPV isolates were transmitted by chip budding to
      GF 305 seedlings and mechanically to selected herbaceous test plants. The
      isolates differed in severity of infection, host range and symptomatology. A
      subgroup differentiation of 43 isolates from 22 localities of western and middle
      Slovakia was accomplished using reverse transcription-polymerase chain reaction
      (RT-PCR), immunocapture RT-PCR (IC-RT-PCR) and restriction analysis. These assays
      confirmed the presence of isolates belonging to PPV-M and PPV-D subgroups. PPV-M
      and PPV-D isolates were almost equally represented in tested samples. Tests of
      subgroup variability of PPV isolates from infected tolerant plum cultivars showed
      great predominance of PPV-M isolates.

PMID- 10073225
TI  - Aphid species--vectors of plum pox virus.
AB  - Plum pox virus (PPV) is widely spread by natural vectors present in plum
      orchards. The efficiency of transmission is dependent on the frequency of the
      occurrence of vectors and the cultivar susceptibility to this pathogen. Having in
      view that PPV has a wide range of annual and multiannual host plants and vectors,
      there is great concern for obtaining PPV-resistant cultivars. This report deals
      with the following vectors: Hyalopterus pruni, Brachycaudus cardui, Brachycaudus
      helichrysi. Myzus persicae and Phorodon humuli aphids, and Aculus fockeni mite.
      Seven different cultivars of Prunus domestica were utilized. To assess the virus
      transmission rate, 50-100 individual vectors per tree were used. The treatment of
      the trees was performed every four weeks and then the disease symptoms were
      observed. PPV was transmitted by all vectors studied, the rate ranging in
      dependence on the susceptibility of cultivars used. Thus, in cvs. Centenar,
      Pescarus, d'Agen, Stanley and Tuleu Gras, the transmission rate ranged from 20%
      to 60%, while in susceptible cvs. Vanat romanesc and Vanat de Italia--from 40% to
      80%.

PMID- 10073226
TI  - High resistance and control of biological risks in transgenic plants expressing
      modified plum pox virus coat protein.
AB  - Transgenic plums transformed with the plum pox virus coat protein (PPV CP) gene
      displayed a resistance to the sharka disease (Ravelonandro et al., 1997).
      However, the expression of PPV CP in transgenic plants may lead to
      complementation of deficient characteristic of an incoming potyvirus. Indeed, an
      aphid-intransmissible strain of zucchini yellow mosaic virus (ZYMV-NAT) could be
      transmitted when encapsidated by the engineered PPV CP (Lecoq et al., 1993). To
      control such a risk, new PPV CP constructs were designed and introduced into
      Nicotiana benthamiana genome. In the first construct, the DAG amino acid triplet
      involved in the potyvirus aphid-transmission was deleted. The second construct
      encoded a truncated PPV CP lacking its first 140 amino acids. In the last
      construct, the nucleotides encoding the charged amino-acids R220, Q221 and D264
      localized in the core of the PPV CP were removed. A bacterial expression system
      was developed to show that these deletions prevent the assembly of the PPV CP
      subunits. For each construct, several transgenic lines were produced and first
      challenged with several strains of PPV. Two phenotypes of resistance were
      observed: recovery and immunity. Their biochemical characterization showed that
      the resistance was RNA-mediated and therefore can be classified as homology
      dependent (Jacquet et al., 1998a). Resistant lines producing high level of wild
      type or modified PPV CP were then inoculated with ZYMV-NAT to perform an aphid
      transmission assay. Results of these experiments demonstrated that the use of
      modified forms of PPV CP genes in transgenic plants provide a good way to control
      the biological risks associated with heteroencapsidation (Jacquet et al., 1998b).

PMID- 10073227
TI  - Mineral nutrition of plum trees as an important factor of protection against plum
      pox virus disease.
AB  - The experimental results obtained from a fruit garden at Krajne pointed out a
      different content of macrobiogenic elements in the leaves of plum trees infected
      with plum pox virus (PPV) as compared to healthy ones. Mineral nutrition of
      diseased trees was characteristic by lower relational values of topical levels of
      macrobiogenic elements especially those of N/P, N/K, (Ca + Mg)/K, and
      (N/P)/(N/K).

PMID- 10073228
TI  - Preliminary report on the apparent breaking of resistance of a transgenic plum by
      chip bud inoculation of plum pox virus PPV-S.
AB  - Five transgenic clones of Prunus domestica L. containing plum pox virus (PPV)
      coat protein (CP) gene and one non-transformed control clone were challenged with
      PPV-S in the field. Symptoms developed on C2, C3, C4, C6 and B70146 but not C5
      trees inoculated by chip budding (CBI) (2/2, 2/2, 1/1, 2/2 and 2/2,
      positive/inoculated) in the first summer after inoculation. However, in the
      second year, symptoms appeared on CBI C5 trees. The presence of the virus in the
      plants was confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse
      transcription-polymerase chain reaction (RT-PCR) amplification of a fragment of
      viral polymerase gene. During two years, symptoms of infection developed on 3 to
      4 of 8 non-inoculated trees of clones C2, C3, C4, C6 and B70146. Eight non
      inoculated C5 trees remained symptomless and ELISA-negative as of spring 1998, in
      spite of the presence of aphid vectors and inoculum sources.

PMID- 10073229
TI  - New results concerning the plum pox virus epidemiology and resistance of plum
      cultivars, hybrids and rootstocks.
AB  - Our recent results on the plum pox virus (PPV) epidemiology show that PPV spreads
      very rapidly in plum tree plantations in the contaminated areas. A clearing of
      the PPV-infected trees reduces significantly the spread of the virus but does not
      eliminate the disease. Some plum tree cultivars, hybrids and rootstocks (Scoldus,
      Alina, Cristi, BN 1/8Fl, BN 2Gr. etc) showing field resistance could not be
      infected with PPV by natural way. However, they could be infected with PPV by
      artificial inoculation except for the plum tree cv. Local of Dragasani and the BN
      4Kr myrobalan, which proved to be immune to PPV. PPV was not transmitted through
      seeds in plum tree and myrobalan in the nursery. The Hyalopterus pruni aphids
      were found PPV-positive by an enzyme-linked immunosorbent assay (ELISA).

PMID- 10073230
TI  - Production of a monoclonal antibody specific to the El Amar strain of plum pox
      virus.
AB  - Plum pox virus (PPV) isolates are grouped into three clusters differentiated by
      biological, serological, molecular and epidemiological characteristics: Marcus
      (M), Dideron (D) and Cherry (C). The El Amar (EA) isolate that does not fit any
      of the above groups is also known. Monoclonal antibodies (MAbs) that specifically
      recognize M, D, and C strains of PPV are already available. To complete the set
      of PPV strain-specific serological reagents, MAbs against the EA isolate were
      raised by immunizing BALB/c mice and fusing their spleen cells with NS0/1 myeloma
      cells. After a preliminary characterization by double-antibody sandwich enzyme
      linked immunosorbent assay (DAS-ELISA), 1 of 13 selected MAbs proved to be EA
      strain-specific. This MAb (EA24) reacted equally well with a homologous antigen
      and several PPV isolates from Egyptian apricot trees, supporting the hypothesis
      of an additional specific PPV group. MAb EA24 did not react either with about a
      hundred PPV isolates belonging to the D and M groups or with PPV-SwC and PPV-SoC
      isolates belonging to the C group. The strain specificity of MAb EA24 was
      confirmed by Western blot analysis and immunoelectron microscopy. We conclude
      that there is now available a set of MAbs which are highly specific to the four
      currently known groups of PPV strains.

PMID- 10073231
TI  - Detection and serotyping of Mediterranean plum pox virus isolates by means of
      strain-specific monoclonal antibodies.
AB  - Plum pox virus (PPV) is a major threat to the expanding Mediterranean stone fruit
      industry. In order to control the plum pox disease it is of utmost importance to
      detect early PPV foci and to identify the PPV isolates involved. A survey was
      therefore carried out in Albania, Cyprus, Egypt, Greece, Italy and Turkey by a
      double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) with the
      following monoclonal antibodies (MAbs): 5B (universal), 4DG5 (PPV-D-specific), AL
      (PPV-M-specific), TUV and AC (PPV-C-specific), and EA24 (PPV-El Amar-specific). A
      hundred and seventy Mediterranean PPV isolates were tested for strain type. PPV-M
      was detected in Albania, Cyprus, Greece, Italy, and Turkey; PPV-D was detected in
      Albania and Italy, whereas samples with natural mixtures of both strains were
      found in a couple of orchards in Albania. Seven PPV isolates from apricots in two
      Egyptian localities were recognized only by MAb EA24. In conclusion, DAS-ELISA
      with a combination of the universal MAb5B and the MAbs specific to the four PPV
      serotypes currently known (M, D, C and El Amar) is an efficient tool for a
      simple, sensitive and routine detection of PPV and discrimination of its
      serotypes.

PMID- 10073232
TI  - Molecular variability of Czech plum pox virus isolates.
AB  - Seventy-two Czech plum pox virus (PPV) isolates from different hosts were tested
      by double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). In
      addition, the coat protein mobility and the RsaI restriction fragment length
      polymorphism (RFLP) pattern of reverse transcription-polymerase chain reaction
      (RT-PCR) amplified coat protein (CP) gene fragment of the isolates were analysed.
      Both PPV-D and PPV-M serotypes were found in the Czech Republic. The results
      obtained by these different methods were in accord with exception of a few cases
      probably caused by mutation or recombination.

PMID- 10073233
TI  - Testing of plum germplasm for sensitivity to plum pox.
AB  - A long-term orchard experiment with a broad assortment of plum cultivars aimed to
      screen their sensitivity to plum pox virus (PPV) was established in 1991. For
      this purpose, 207 cultivars to be artificially infected with PPV at a permanent
      site were chosen. The serotype M of PPV from a tree of cv. Domestic Prune, which
      had not been contaminated by other viruses, was used as a source of the
      infection. Three buds infected with PPV were budded on 1-year-old trees. In the
      course of experiment the following results were obtained. The highest
      transmission of PPV was recorded in the first year after infection, when 69.5% of
      positive trees were detected by enzyme-linked immunosorbent assay (ELISA). After
      4 years, the absence of PPV was still detected in 11.2% of the cultivars. These
      were reinfected with the same source of PPV in 1996. In 1998, there were 92.9% of
      trees contaminated by sharka. Seven years after infection with PPV, a dieback of
      41 trees took place. In the most cases a presence of an ilarvirus in the plant
      was detected. The PPV infection was not transferred further on cvs Bila trnecka,
      Francia Naranes, Large Sugar Prune, Reine Claude Diaphane, Renkloda Jandacek,
      Scoldus, Tarnina x Kirke, Valasska trnecka and K-4. There were 75% of trees
      fruited in 1997. Only 28 cultivars had no symptoms of PPV on fruits. A
      statistically significant relationship between the incidence of PPV after the
      artificial infection and a the presence of prunus necrotic ring spot virus
      (PNRSV). The presence of PNRSV reduced the transmission of PPV. Relationships
      between PPV and prune dwarf virus (PDV), and between PPV and (PDV + PNRSV) were
      not statistically significant.

PMID- 10073234
TI  - Detection of plum pox virus in apricot seeds.
AB  - Twelve different apricot selection trees from a germplasm collection naturally
      infected with plum pox virus (PPV) were chosen to investigate the role of seeds
      in the epidemiology of this dangerous pathogen. All the considered plants showed
      typical symptoms on leaves and fruits and were positive in enzyme-linked
      immunosorbent assay (ELISA). The virus was characterized by immunocapture reverse
      transcription-polymerase chain reaction (IC-RT-PCR) followed by restriction
      fragment length polymorphism (RFLP) analysis with RsaI enzyme as a PPV-D isolate.
      The presence of PPV was checked on fully ripe seeds and seedlings. One half of
      the seed stock was analysed immediately by ELISA and IC-RT-PCR tests: the
      cotyledons containing also the embryo were separated from the teguments. The
      other half of the seed stock was germinated and maintained in an insect-proof
      screenhouse over a 2-year period. PPV was detected by ELISA only in the seed coat
      while by IC-RT-PCR also in cotyledons. Seedlings from infected seeds did not show
      any typical symptoms and were PPV-negative in serological and molecular assays.
      So far, the presence of PPV in seeds seems to play no role in its epidemiology.

PMID- 10073235
TI  - Relative concentration of plum pox virus in leaves and flowers of some Prunus
      species and cultivars.
AB  - The relative concentration of plum pox virus (PPV) in leaves and flowers of plum,
      damson, myrobalan, blackthorn, apricot and peach trees was determined by enzyme
      linked immunosorbent assay (ELISA) and expressed as the lowest dilution with
      positive reaction. Significant differences in relative PPV concentration were
      found in leaves among individual Prunus species naturally or artificially
      infected with the virus. The highest relative PPV concentration was found in
      blackthorns (7.81 x 10(-4)), common plum and apricot (1.56 x 10(-3) for the both
      latters). Wild growing PPV-infected plums and blackthorns can be considered
      equally important source of sharka infection as PPV-susceptible cultivars of
      plums, apricots and peaches. High PPV concentration in flowers is of diagnostical
      value. High variability of relative PPV concentration was observed inside the
      species among individual cultivars. Susceptible cultivars were characteristic by
      high relative PPV concentration, e.g. apricot cvs. Vegama (9.8 x 10(-5)) and
      Velkopavlovicka (1.95 x 10(-4)), and peach cvs. Maria Emilia (7.81 x 10(-4)) and
      Harbinger (1.56 x 10(-3)). On the other hand, cultivars resistant to PPV were
      characteristic by very low relative PPV concentration, e.g. apricot cv. Stark
      Early Orange (5 x 10(-2)) and peach cvs. Envoy (5 x 10(-2)) and Favorita
      Morettini (2.5 x 10(-2)). The highest relative PPV concentration was found in
      young trees newly infected with PPV.

PMID- 10073236
TI  - Restriction fragment length polymorphism differentiation of plum pox virus
      isolates.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) technique and
      restriction fragment length polymorphism (RFLP) analysis were used to analyse six
      isolates of plum pox virus (PPV). Whole coat protein (CP) gene was amplified in
      four isolates using the unipoty-polyT primer pari. PPV-D was identified by RFLP
      analysis using SfuI and DraI enzymes in two of the isolates. Two isolates of PPV
      M strain yielded RT-PCR products which could not be digested by the two enzymes.
      Other isolates were subjected to RT-PCR using P1-P2 primers. The specificity of
      the RT-PCR products was confirmed by AluI digestion, while RsaI digestion enabled
      strain differentiation. No mixed infection was found.

PMID- 10073237
TI  - Characterization of phenotype resistance to plum pox of transgenic plums
      expressing plum pox virus capsid gene.
AB  - Resistance to plum pox virus (PPV) infection can be obtained in transgenic plants
      that express the virus capsid gene. An Agrobacterium-mediated transformation was
      used to introduce the PPV capsid gene into Prunus domestica plants. Over 11
      regenerated plants (clones) were observed for the development of the disease
      symptoms and analysed for the presence of PPV by enzyme-linked immunosorbent
      assay (ELISA), Western blot analysis, and reverse transcription-polymerase chain
      reaction (RT-PCR) through 4 dormancy cycles. The level of protection against PPV
      was determined in the transformed plants, non-transformed plants, and a control
      transgenic plant "transformed" with the plasmid vector alone. One clone, C-5,
      appeared fully protected, while PT-6 and C-4 clones accumulated a low
      concentration of virus and the rest of the clones was entirely susceptible.
      Little is known about the mechanisms of resistance to virus infection in
      transgenic woody plants. To investigate this aspect, comparative studies based on
      the characteristics of resistant and susceptible clones have been started. A
      question, whether the phenotype resistance of clone C-5 is similar to that
      observed in transgenic herbaceous plants or not, has been addressed. Recent
      progress in this investigation is presented.

PMID- 10073238
TI  - Agroclimatical analysis of plum pox virus spread in Slovakia.
AB  - In this report, the plum pox virus (PPV) spread from the point of view of
      agroclimatical conditions on the territory of Slovakia is analysed. The worst
      condition for the PPV spread was found in a warm macroregion. The air temperature
      sum in this macroregion during vegetative period ranged from 2400 to 3100 degrees
      C. The worst condition for the PPV spread was found in dry subregions of the
      macroregion. These were defined by differences between potential
      evapotranspiration and rainfall sums which ranged from 50 to 150 mm during summer
      months (from June to August). The decrease in air temperature sums and the
      increase of moisture in the environment as well as the severity of winter period
      was found to support the occurrence and spread of PPV.

PMID- 10073240
TI  - [The problem of double publication].

PMID- 10073239
TI  - Detection of plum pox virus by enzyme-linked immunosorbent assay in some apricot
      and peach varieties and hybrids in Romania.
AB  - Plum pox virus (PPV) is a potyvirus widely spread in many species of the Prunus
      genus such as plum, apricot, peach, sweet cherry and others. This potyvirus
      causes great damage to stone fruit trees in Romania and other European countries
      as Hungary, Italy, Czech Republic, France, Spain, Greece, Turkey, and Slovak
      Republic. The Research Station for Fruit Tree Growing Baneasa in Bucharest has
      realized many studies on the epidemiology and spread of PPV and also on the
      disease symptomatology and detection possibilities. The control of sharka disease
      by sanitary selection measures requires corresponding detection techniques. The
      aim of this study was to determine the presence or absence of PPV in some apricot
      and peach varieties and hybrids in 1995-1997 by the enzyme-linked immunosorbent
      assay (ELISA) and to verify if some of our biological materials evaluated as
      symptom-free under field conditions for many years are also virus-free and can be
      considered healthy.

PMID- 10073241
TI  - [Point-of-care-testing--the intensive care laboratory].
AB  - After successful centralization of laboratory analyses since more than 30 years,
      advances in biosensors, microprocessors, measurement of undiluted whole blood and
      miniaturization of laboratory analyzers are leading nowadays more and more to a
      re-decentralization in the laboratory medicine. Point-of-care-testing (POCT),
      which is defined as any laboratory test performed outside central or
      decentralized laboratories, is becoming more and more popular. The theoretical
      advantages of POCT are faster turn-around-times (TAT), more rapid medical
      decisions, avoidance of sample identification and sample transport problems and
      the need of only small specimen volumes. These advantages are frequently
      mentioned, but are not associated with a clear clinical benefit. The
      disadvantages of POCT such as incorrect handling and/or maintenance of the
      analyzers by nontrained clinical staff, inadequate or even absent calibrations
      and/or quality controls, lack of cost-effectiveness because of an increased
      number of analyzers and more expensive reagents, insufficient documentation and
      difficult comparability of the obtained POCT-results with routine laboratory
      results, are strongly evident. According to the authors' opinion the decision for
      the establishing of POCT has only to be made in a close co-operation between
      physicians and laboratorians in order to vouch for necessity and high quality of
      the analyses. Taking the local situation into consideration (24-h-central
      laboratory, etc.) the spectrum of parameters measured by means of POCT should be
      rigorously restricted to the vital functions. Such analytes should be: hemoglobin
      or hematocrit, activated whole blood clotting time, blood gases, sodium,
      potassium, ionized calcium, glucose, creatinine, ammonia and lactate.

PMID- 10073242
TI  - [Preoperative changes in fluid filtration capacity in patients undergoing
      vascular surgery].
AB  - Patients undergoing major vascular surgery frequently require a substantial
      intraoperative fluid replacement to assure hemodynamic stability, which is in
      excess of the expected fluid requirements due to starving, blood and insensible
      losses. This leads to a positive fluid balance which can not be readily
      explained. METHOD: We have used venous congestion plethysmography (VCP) a non
      invasive method for measurement of microvascular parameters in limbs to
      investigate the changes in microvascular permeability (FFK) and the balance of
      Starling forces of patients undergoing surgery for unilateral femoral artery
      reconstruction (FEM) under epidural anaesthesia or abdominal aortic aneurysm
      repair (AAA) under general anaesthesia. The control group consisted of patients
      scheduled for inguinal hernia repair or hand surgery under general anaesthesia.
      All patients were measured 24 hours pre-operatively, immediately after the
      induction of anaesthesia or completion of epidural anaesthesia and on the 1st,
      5th and 10th postoperative day. The perioperative patient management followed a
      standard protocol and all patients with vascular disease were invasively
      monitored using indwelling arterial lines and central venous catheters.
      Continuous infusion of Ringers lactate and 6% Dextran 60 was sustained during the
      induction period. Each patient gave informed consent. RESULTS: Preoperatively we
      found no significant difference in the mean FFK-values of controls (4.1 +/- 0.4,
      ml.min-1 100 ml tissue-1 mmHg-1 x 10(-3) = FFKU), the AAA (3.6 +/- 0.3 FFKU) and
      FEM (4.2 +/- 0.3 FFKU). After induction of anaesthesia the mean FFK value in the
      controls fell to 3.5 +/- 0.5 FFKU (p = 0.07), whereas in the AAA patients we
      observed a significant increase to 4.7 +/- 0.2 FFKU (p < 0.005) and after
      epidural anaesthesia in FEM to 5.5 +/- 0.4 FFKU (p < 0.001) respectively. Those
      post anaesthetic FFK values where significantly higher in FEM and AAA than in the
      controls (p < 0.02). In AAA we found a significant positive correlation between
      the increase in FFK and the intraoperative fluid balance (r2 = 0.69, p < 0.01).
      No such correlation was found in controls and FEM. The postoperative values of
      FFK where unchanged in the control group, whereas a further increase was seen in
      both patient groups with vascular disease, with a maximum in AAA on the 1st
      postoperative day (to 5.4 +/- 0.4 FFKU mean both legs) and the 5th postoperative
      day in FEM (to 7.3 +/- 1.7 non-ischemic leg, 7.1 +/- 1.2 ischemic leg FFKU). In
      both groups normal FFK values where found on the 10th day after the operation.
      CONCLUSION: The data presented suggests an increase in extravascular fluid loss
      in patients undergoing vascular surgery, which becomes evident after the
      induction of general anaesthesia or completion of epidural anaesthesia. The
      positive correlation with the intraoperative fluid requirements may partially
      explain the often reported large intraoperative fluid requirements of patients
      undergoing AAA repair. The fact that the maximum change in fluid filtration
      capacity is found postoperatively may be explained by the additional effect of an
      ischemia/reperfusion injury in response to both the clamping an declamping of the
      artery and the increase in arterial blood flow to the limb due to the successful
      reconstruction of the blood vessel.

PMID- 10073243
TI  - [The effect of low droperidol dosages on postoperative anxiety, internal tension,
      general mood and PONV].
AB  - BACKGROUND: Droperidol even in low doses such as 0.5 mg to 1.25 mg can increase
      postoperative anxiety and state of tension. The aim of this study was to
      determine whether these side effects occur frequently following low-dose
      droperidol and to see whether these are dose related. METHODS: 184 female in- and
      outpatients ASA grade 1 and 2 undergoing gynaecological laparoscopy were
      recruited to this prospective, double-blind study. General anaesthesia was
      standardized (induction with thiopentone, fentanyl 2 micrograms/kg and vecuronium
      0.1 mg/kg, tracheal intubation, maintainance with enflurane in N2O/O2). Patients
      were randomly allocated to receive saline (n = 45), 0.625 mg (n = 46), 1.25 mg (n
      = 47) or 2.5 mg (n = 46) droperidol i.v. 10 minutes before the end of surgery.
      1,3,6, and 24 hours postoperatively, the patients' anxiety, state of tension and
      overall mood was evaluated using two psychological questionnaires which had been
      tested for the perioperative period (Erlanger anxiety and tension-scale/BSKE-EWL
      test). Sedation was evaluated by the staff of the recovery room. In addition,
      postoperative nausea and vomiting (PONV) was assessed using a 100 mm visual
      analogue scale and by counting the episodes of retching or vomiting. PONV was
      then rated over the whole observation period as none, mild, moderate or severe
      using a fixed scoring algorithm. Statistical analysis was performed using the
      ANOVA and the chi2-test. RESULTS: The patients did not differ with regard to
      biometric data, duration of surgery and anaesthesia. The postoperative scores for
      anxiety, state of tension and overall mood were not different between the groups
      at any observation time (Fig. 1: anxiety and tension: P = 0.5687; figure 2:
      overall mood: P = 0.0647). Quality of sleep in the first night after surgery was
      the same in all groups (Table 2 and 3). Sedation was not significantly different
      (Table 4; P = 0.0704). Furthermore, duration of stay in the recovery room did not
      differ (P = 0.4353). On the other hand, three patients from the 2.5 mg droperidol
      group had to stay unexpectedly on the ward overnight, because they had been too
      much sedated to be discharged at home. This was not the case with any patient
      from the other groups. Compared to placebo, PONV over the whole 24 h observation
      period was significantly reduced by droperidol (Fig. 3; P = 0.0338): completely
      free from PONV: placebo: 41.3%, 0.625 mg droperidol: 67.4%, 1.25 mg droperidol:
      53.2%, 2.5 mg droperidol: 71.7%. Also the severity of PONV was reduced.
      CONCLUSION: In gynaecological laparoscopy under general anaesthesia with tracheal
      intubation, we recommend droperidol 0.625 mg in the prevention of PONV, as it
      reduces PONV as well as 2.5 mg with no severe sedation in this dosage.
      Psychological side effects did not occur more frequently after droperidol
      compared to placebo in any of the investigated dosages.

PMID- 10073244
TI  - [History of the development of intensive care medicine. Contemporary
      considerations. 2. Structural development of internal intensive care medicine].

PMID- 10073245
TI  - [Validating of a transesophageal ultrasonic-Doppler probe to the detection of air
      in the venous blood. Remarks on the paper of D. Henze et al. Anaesthesist (1998)
      47:406-408].

PMID- 10073246
TI  - [Intraoperative fluid therapy in infants and young children].

PMID- 10073247
TI  - [Anesthesiologic technical problems in procedures with open MRI. Results
      following 104 anesthesias].

PMID- 10073249
TI  - [Limitations of preclinical emergency medicine from the legal viewpoint].
AB  - Revised and Annotated Version of the Author's Lecture held at the 13th Annual
      Meeting on Emergency Care Medicine on 14 March 1998 at Baden-baden, Germany. This
      article highlights the limitations of preclinical emergency care medicine from a
      legal viewpoint. Among other problems, focus is also on the problem whether a
      particular emergency care measure can be expected from the emergency physician.
      Much attention is devoted to a discussion on treating a patient against his will,
      this constituting a differentiated borderline case in emergency medicine. Another
      equally differentiated problem concerns the economic aspects--for example,
      whether an emergency treatment pays returns in terms of economy. This is no
      limitation in individual cases where emergency treatment is medically indicated,
      but it does exercise an influence on pre-planning the security level of emergency
      care services. There are no limitations for emergency services from a legal point
      of view imposed by the patient's age or his or her domicile in a home for the
      aged or infirm.

PMID- 10073250
TI  - [Blood gas analysis in interhospital transfer--a useful extension of respiratory
      monitoring?].
AB  - OBJECTIVE: Investigation of blood gas analysis during hospital-to-hospital
      transport of ventilated ICU-patients to detect critical events, changes of gas
      exchange and reliability of non-invasive monitoring. METHODS: 47 ventilated
      patients (age 9-76 years, mean 50 years, diagnosis: ARDS = 16, intracranial
      bleeding = 14, severe trauma = 4, acute hemodynamic failure = 3, others = 10),
      transported by a special physician staffed intensive care ambulance using
      invasive hemodynamic monitoring. Blood gas analysis was performed before and
      during transport every 30 minutes and respirator mode, vital signs and events
      were documented. RESULTS: In 19 (40.4%) patients there were critical events
      during transport (paO2 < 70 mmHg, paCO2 < 25 mmHg, paCO2 > 55 mmHg, pH < 7.30, pH
      > 7.55). In 4 patients with PaO2 < 70 mmHg there was SpO2 > or = 97% (by
      pulsoximetry), correlation between SaO2 (invasive) and SpO2 (by pulsoximetry) was
      r = 0.81 (P < 0.001) with a maximum difference of 8 percent. In several patients
      critical changes of condition could be recognized in an early stage by blood gas
      analysis. CONCLUSIONS: Blood gas analysis during hospital-to-hospital transport
      of ICU-patients can be performed easily and allows to optimize artificial
      ventilation and to recognize earlier and safer severe problems of gas exchange.

PMID- 10073251
TI  - [Experiences fo three year's routine operation of an anesthesia information
      management system (AIMS) at a university clinic in Giessin].
AB  - PURPOSE: In 1994, the Department of Anaesthesiology and Intensive Care Medicine
      of the Justus Liebig University at Giessen decided to install an Anaesthesia
      Information Management System (AIMS). Individual aspects and results from routine
      operation are presented, demonstrating the quality of the documentation and the
      value of information at the anaesthesiological workstation. The paper discusses
      which adaptations are necessary according to the experience gathered. METHODS:
      For the installation of the system Apple Macintosh Clients (Apple Computer, Inc.,
      Cupertino, California) and a File Server were integrated into the partially
      existing hospital network. The hospital network had to be enlarged during the
      project according to the Anaesthesiological requirements. The software of the
      Hospital Information System (HIS) and an HTML browser were installed at
      individual workstation computers in addition to the Anaesthesia documentation
      software NarkoData (ProLogic GmbH, Erkrath). The remote control software Timbuktu
      (Farallon, Alameda, USA) has been added to facilitate remote administration. The
      file administration programme FileWave (Wave Research, Berkeley, USA) is used for
      file distribution. Since 1995, all anaesthesia procedures have been documented
      with the system, either by online or postoperative recording. Since 1997, the
      recorded information has been stored in a relational Oracle 7 data bank (Oracle
      Corporation). RESULTS: From 1995 to 1997, 60,405 anaesthesiological procedures
      have been recorded with the help of this AIMS at 111 decentralised workstations.
      In 1997, 87.8% of the 21,130 performed anaesthesia procedures have been recorded
      online with the system and 12.2% postoperatively. From 1995 to 1997, the number
      of recorded procedures increased by 6.4% from 19,854 to 21,130. Because of
      lacking interfaces at some patient monitoring stations, the automatic recording
      of patient data could only be implemented at 69 workstations (62%). With the
      corresponding access rights, important patient information from the HIS
      (diagnoses, laboratory results, etc.), records of previous Anaesthesia
      procedures, numerous statistics, and the whole information from the hospital's
      intranet (including e-mail) are available at the anaesthesiological workstation
      at any time. CONCLUSION: The implementation of the AIMS and an effective user
      support have been able to increase significantly the quality of documentation,
      the flow of information at the anaesthesia workplace and the number of recorded
      Anaesthesia procedures. All recorded data can be analysed immediately The
      expansion of the automatic data transfer from the patient monitoring, interfaces
      to other computer subsystems of the hospital and a practicable evaluation
      programme are necessary for further enhancing the efficiency of the AIMS.

PMID- 10073253
TI  - [Hyperfunction and hypofunction of the thyroid gland].

PMID- 10073252
TI  - [Statistics and evaluation of a graphic SQL user interface in an anesthesia
      information management system (AIMS)].
AB  - PURPOSE: Since 1997, the Anaesthesia Information Management Systems (AIMS) in our
      department has produced extensive data material (DGAI core data, vital sign
      parameters, respiratory parameters, material consumed, etc.) which is stored in a
      relational data bank. The processing of this data by means of SQL queries was
      restricted to a few persons with special knowledge only. It was the objective of
      the project to create an evaluation tool which enables each member of the
      department to enter queries concerning topics such as efficiency records, quality
      management, training and research at any time. The tool was also intended to
      present results in an adequate form. METHODS: Since 1997, the data of the
      performed anaesthesia procedures have been recorded using the online anaesthesia
      documentation software NarkoData Version 4 (ProLogic GmbH, Erkrath) within the
      AIMS. The recorded data sets have been imported into a relational Oracle data
      bank (Oracle Corporation). The commercial programme Voyant (Brossco Systems,
      Espoo, Finland) enables for the user to formulate SQL-requests (Structured Query
      Language) with the help of a graphic user interface and to present the results in
      a variety of graphics and tables. Repetition of the evaluation using the current
      data is possible at any time. RESULTS: During 1997 and the first quarter of 1998,
      the data of 26,030 anaesthesia procedures have been registered and stored in the
      anaesthesiological data base. 235 queries could be formulated with the SQL
      capable graphic tool Voyant. They are available to each member of the department
      by the application of NarkoStatistik (IMS GmbH, Giessen) within the AIMS,
      together with the corresponding documentation (HTML pages). The query catalogue
      covers the main topics of efficiency, quality management, organisation, diagnoses
      and surgery, pre-, intra- and postoperative data and day-care unit. Even without
      much previous experience with the system it is possible to carry out evaluations
      with the current data at selected AIMS terminals. Queries concerning other
      subjects can be created and can be integrated into the existing query catalogue.
      CONCLUSION: With the described application we are able to establish an evaluation
      tool which fulfils our expectations regarding user friendliness and the subjects
      the queries can cover. Today it has a central position within the AIMS. In
      addition to the anaesthesia documentation software and the data bank structure,
      the efficiency of an AIMS is mainly influenced by the corresponding evaluation
      tool.

PMID- 10073254
TI  - [Hyperfunction and hypofunction of the thyroid gland from the anesthesiologist's
      viewpoint].

PMID- 10073255
TI  - [Hyperthyroidism from the viewpoint of the surgeon].

PMID- 10073256
TI  - [Operative and anesthesiologic problems in hyperthyroidism from the viewpoint of
      the internist].

PMID- 10073257
TI  - [Anesthesia in dental, oral, jaw, facial, and ophthalmic surgery; therapeutics of
      the neck, nose, and eye . 1. General and specific aspects in dental, oral, jaw
      and facial surgery].

PMID- 10073258
TI  - [Diagnosis, procedures and conservative therapy of a bronchial rupture after
      intubation with double-lumen tube].
AB  - Bronchial rupture is a rare but severe complication of intubation with a double
      lumen tube. Cardinal symptoms are mediastinal and subcutaneous emphysema as well
      as pneumothorax. Larger injuries result in an air leak and the endtidal carbon
      dioxide decreases. The gas exchange may worsen drastically when mucosal prolapse
      or bronchial haemorrhagia lead to bronchial occlusion. Mediastinitis or sepsis
      can be the sequel of the opened mediastinum. If bronchial injury is suspected
      probably fibreoptic bronchoscopy is indicated. We report on a case of bronchial
      rupture due to overinflation of the endobronchial cuff or movement of the
      inflated cuff when repositioning the patient. The conservative therapy was
      successful in spite of the fact that surgical intervention is recommended in the
      literature following bronchial rupture. To avoid tracheobronchial injuries an
      adequate tubus size must be selected. The more flexible polyvinylchloride (PVC)
      tubes without a carinal hook should be preferred to the Carlens tube. An
      atraumatic intubation is promoted by leaving the stylet inside after the tip of
      the tube has passed the vocal cords. To identify the minimum occlusive pressure
      of the endobronchial cuff for lung isolation different methods are described and
      should be used. The cuff has to be deflated when the patient is repositioned and
      when one-lung-ventilation is not required. Tumours of the tracheobronchial tree
      and weakness of the bronchial wall caused by steroid hormone therapy or COPD may
      increase the risk of tracheobronchial laceration.

PMID- 10073259
TI  - [Current court decisions--their importance for anesthetists in brief].

PMID- 10073260
TI  - Cyclosporine treatment of glomerular diseases.
AB  - Cyclosporine-A is primary therapy for organ transplantation. Its
      immunosuppressive effect might suggest a therapeutic role in autoimmune diseases,
      including several idiopathic and secondary glomerular conditions. Various forms
      of idiopathic nephrotic syndrome, including focal segmental glomerulosclerosis
      (FSGS), minimal change disease (MCD), and membranous nephropathy (MN), may
      respond well to cyclosporine in selected patients. However, frequent relapse
      limits its use to those who have failed to respond to, or were intolerant of,
      steroids or cytotoxics. Cyclosporine's efficacy in other glomerulopathies, such
      as IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN)
      remains poorly studied and, given the risk of nephrotoxicity, cannot be
      recommended for treatment of these entities until further data are available.
      Cyclosporine demonstrates some efficacy in treating proliferative lupus nephritis
      and, based on pilot study data, membranous lupus as well. Again, given relapse
      rates and potential nephrotoxicity, it should be used only in combination with
      azathioprine and steroids, assuming cytotoxic therapy has failed. Finally,
      cyclosporine toxicity is briefly reviewed.

PMID- 10073261
TI  - Arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a new form of cardiomyopathy
      probably more frequent than commonly reported. It is a rare but important cause
      of sudden arrhythmic death in young, otherwise healthy persons, as well as a
      subtle cause of congestive heart failure. It may lead to temporary incapacitation
      with catastrophic consequences. Proper electrocardiographic criteria,
      echocardiography, nuclear medicine, or magnetic resonance imaging could identify
      most of these individuals. With the exception of full-thickness histological
      examination of the right ventricular free wall, contrast ventriculography remains
      the most definitive standard for a positive diagnosis. The wide clinical spectrum
      of arrhythmogenic right ventricular cardiomyopathies/dysplasia appears to be the
      result of one or possibly two factors: (a) replacement of most of the right
      ventricular myocardium by fat and (b) genetic susceptibility to environmental
      agents (myocarditis). Current treatment modalities include drug therapy, catheter
      or surgical ablative techniques, and modern treatments of congestive heart
      failure. Heart transplant is exceptional. Implantable defibrillators, used alone
      or in combination with drug therapy, will probably play an increasing role in
      ARVD and related cardiomyopathies.

PMID- 10073262
TI  - Intestinal pseudo-obstruction.
AB  - Pseudo-obstruction syndromes are increasingly recognized in clinical practice.
      They result from impairment of intrinsic neuromuscular or extrinsic control of
      gut motility. Typically, pseudo-obstruction syndromes result in features
      suggestive of mechanical obstruction and bowel dilatation in the absence of any
      demonstrable obstruction or mucosal disease. The syndrome may affect any region
      of the gut. Less severe variants without bowel dilatation are diagnosed by
      measurement of gastrointestinal transit and pressure profiles. The aims of
      treatment are restoration of nutrition and hydration, symptom relief,
      normalization of intestinal propulsion with prokinetics, and suppression of
      bacterial overgrowth. Surgery plays a limited role, adjunctive to medical
      treatment, facilitating enteral nutrition and decompression by means of
      jejunostomy. Infrequently, resection of localized disease or intestinal
      transplantation are indicated. The roles of intestinal pacemakers (interstitial
      cells of Cajal) and genetic mutations in the etiology of pseudo-obstruction, as
      well as the cost-benefit ratio of transplantation for pseudo-obstruction, will be
      clarified in the future.

PMID- 10073263
TI  - The ubiquitin-proteasome pathway and pathogenesis of human diseases.
AB  - The ubiquitin-proteasome pathway plays a pivotal role in the degradation of short
      lived and regulatory proteins important in a variety of basic cellular processes,
      including regulation of the cell cycle, modulation of cell surface receptors and
      ion channels, and antigen presentation. The pathway involves an enzymatic cascade
      through which multiple ubiquitin molecules are covalently attached to the protein
      substrate, which is then degraded by the 26S proteasome complex. The pathway has
      been implicated in several forms of malignancy, in the pathogenesis of several
      genetic diseases (including cystic fibrosis, Angelman's syndrome, and Liddle
      syndrome), in immune surveillance/viral pathogenesis, and in the pathology of
      muscle wasting. The molecular mechanisms that underlie these processes are being
      unraveled at present.

PMID- 10073264
TI  - Concept and evaluation of hibernating myocardium.
AB  - Hibernating myocardium is a state of persistently impaired myocardial and left
      ventricular function at rest due to reduced coronary blood flows. It can be
      defined as an exquisitely regulated tissue successfully adapting its activity to
      prevailing circumstances. It has been documented in patients with angina (chronic
      stable and/or unstable), acute myocardial infarction, heart failure and/or severe
      left ventricular dysfunction, and anomalous left coronary artery from the
      pulmonary artery. The diagnosis of hibernating myocardium involves (a)
      documenting left ventricular dysfunction at rest and (b) documenting that there
      is viable myocardium in the area of dysfunction. Tests commonly used for the
      latter are dobutamine echocardiography, 201Tl isotope studies, and positron image
      tomography. Revascularization, either by surgery or by interventional catheter
      techniques, has been shown to improve or normalize the abnormal left ventricular
      function at rest.

PMID- 10073265
TI  - Genetics of hemochromatosis.
AB  - Hereditary hemochromatosis (HHC) is a common autosomal recessive disorder of iron
      metabolism that results in progressive iron overload and can be fatal if
      untreated. The hemochromatosis gene (HFE) was identified by positional cloning in
      1996. Two missense mutations have been described in HFE. The majority of HHC
      patients are homozygous for a cysteine-to-tyrosine substitution (C282Y); however,
      a small number are homozygous for a histidine-to-aspartic-acid substitution
      (H63D) or are heterozygous for both of these mutations. Mechanisms by which C282Y
      and H63D may disrupt the normal functioning of HFE have been suggested, but the
      role of HFE in the process of normal iron metabolism has yet to be clearly
      defined.

PMID- 10073266
TI  - How can physicians keep up-to-date?
AB  - Keeping one's personal fund of knowledge current is one of the most formidable
      challenges that physicians face. This article considers a few strategies that may
      help physicians as they struggle to keep their knowledge up-to-date. Physicians
      need to develop their own goals for staying current, systematically and
      periodically search the literature for high-quality material relevant to the
      topics on their agendas, become facile with critical appraisal of the literature,
      and schedule time for reading. One of the responsibilities of any professional is
      to maintain expertise, and this responsibility is probably nowhere more critical,
      or more difficult, than in the profession of medicine.

PMID- 10073267
TI  - Mitochondrial disorders: clinical and genetic features.
AB  - Virtually all cells in humans depend on mitochondrial oxidative phosphorylation
      to generate energy, accounting for the remarkable diversity of clinical disorders
      associated with mitochondrial DNA mutations. However, certain tissues are
      particularly susceptible to mitochondrial dysfunction, resulting in recognizable
      clinical syndromes. Mitochondrial DNA mutations have been linked to seizures,
      strokes, optic atrophy, neuropathy, myopathy, cardiomyopathy, sensorineural
      hearing loss, diabetes mellitus, and other clinical features. Mitochondrial DNA
      mutations also may play an important role in aging, as well as in common age
      related neurodegenerative disorders such as Parkinson's disease. Therefore, it is
      becoming increasingly important for clinicians to recognize the clinical
      syndromes suggestive of a mitochondrial disorder, and to understand the unique
      features of mitochondrial genetics that complicate diagnosis and genetic
      counseling.

PMID- 10073268
TI  - Heparin-induced thrombocytopenia: a ten-year retrospective.
AB  - The past decade has seen many important advances in the pathogenesis, clinical
      and laboratory diagnosis, and management of heparin-induced thrombocytopenia
      (HIT), one of the most common immune-mediated adverse drug reactions. HIT is
      caused by IgG antibodies that recognize complexes of heparin and platelet factor
      4, leading to platelet activation via platelet Fc gamma IIa receptors. Formation
      of procoagulant, platelet-derived microparticles, and, possibly, activation of
      endothelium generate thrombin in vivo. Thrombin generation helps to explain the
      strong association between HIT and thrombosis, including the newly recognized
      syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when
      acquired protein C deficiency during warfarin treatment of HIT and deep venous
      thrombosis leads to the inability to regulate thrombin generation in the
      microvasculature. The central role of HIT antibodies in causing HIT, as well as
      refinements in laboratory assays to detect these antibodies, means that HIT
      should be considered a clinicopathologic syndrome. The diagnosis can be made
      confidently when one or more typical clinical events (most frequently,
      thrombocytopenia with or without thrombosis) occur in a patient with detectable
      HIT antibodies. The central role of thrombin generation in this syndrome provides
      a rationale for the use of anticoagulants that reduce thrombin generation
      (danaparoid) or inhibit thrombin (lepirudin).

PMID- 10073269
TI  - The biology of cystitis: host and bacterial factors.
AB  - Cystitis is caused by a relatively small number of bacterial species. To colonize
      and grow in the urinary tract, these organisms have developed and acquired
      special properties (virulence factors) that allow them to overcome the defences
      of the urinary tract, particularly clearance by urine flow. These virulence
      factors are unlikely to be required during transmission from host to host, and
      sometimes their constitutive expression may actually be disadvantageous. Such
      factors are therefore regulated by the environment and in a coordinate manner to
      ensure their most appropriate expression for the conditions encountered. This
      review focuses on the biology of the urinary tract and the bacterial properties
      necessary to cause cystitis. The regulation of virulence factors at the different
      stages of the infection is considered, and a general model for the pathogenesis
      of urinary tract infection is proposed.

PMID- 10073270
TI  - Idiopathic ventricular tachycardia.
AB  - Most ventricular tachycardias encountered in clinical practice occur in patients
      who have structural heart disease. Idiopathic ventricular tachycardia refers to
      those arrhythmias that occur in patients without structural heart disease,
      metabolic/electrolyte abnormalities, or the long QT syndrome. Three commonly
      recognized forms of idiopathic ventricular tachycardia include: (a) ventricular
      tachycardia associated with mitral valve prolapse, (b) ventricular tachycardia
      originating from the right ventricular outflow tract, and (c) ventricular
      tachycardia originating from the left ventricle. Recently, a fourth type of
      idiopathic ventricular tachycardia, termed the Brugada syndrome, has been
      identified as responsible for some cases of cardiac arrest in persons without
      apparent structural heart disease. Each form of ventricular tachycardia may be
      considered a discrete syndrome based on its electrocardiographic characteristics,
      mechanisms, responses to pharmacologic intervention, and prognosis (good in most
      cases). Ventricular tachycardias range from the common to the exotic, but all
      represent syndromes with which the internist and general cardiologist should be
      familiar.

PMID- 10073271
TI  - Malaria: new developments in treatment and prevention.
AB  - Malaria still kills some 0.5-2.5 million people per year in the tropics.
      Resistance to the cheap, most commonly used antimalarials continues to spread
      alarmingly and could outpace drug development. The artemisinin derivatives have
      had an important clinical impact both on the treatment of resistant falciparum
      malaria and on the incidence of disease in low-transmission areas. A few
      promising new antimalarials are being tested clinically but there is an
      imperative need for cheap, well-tolerated drugs that can be used in short
      courses, and for strategies to delay the onset of drug resistance. Bed nets have
      been shown to reduce the incidence of severe malaria in many areas but an
      effective vaccine is urgently needed.

PMID- 10073272
TI  - Dialysis or transplantation: fitting the treatment to the patient.
AB  - Early referral of the patient with chronic renal failure will give the
      nephrologist time to fit the treatment to the patient. Planning for dialysis and
      transplantation should be undertaken concurrently. If the patient is not of
      advanced age and is not afflicted with severe comorbid illness, renal
      transplantation is the preferred form of renal replacement therapy. Living donor
      transplantation is preferred to cadaveric transplantation. For the patient who
      awaits or who cannot undergo transplantation, either peritoneal dialysis or
      hemodialysis may be chosen. Although the mortality rate for peritoneal dialysis
      appears to be higher than that for hemodialysis, especially among elderly
      diabetic patients, peritoneal dialysis remains an acceptable therapy for the
      highly motivated patient. In the United States, the mortality rate for chronic
      dialysis patients is high. We expect mortality rates for both peritoneal dialysis
      and hemodialysis to fall, however, as we strive to achieve optimal solute
      clearance and to more effectively treat comorbid illness.

PMID- 10073273
TI  - Screening for prostate cancer: the roles of science, policy, and opinion in
      determining what is best for patients.
AB  - Controversy over screening for prostate cancer involves both scientific and
      policy considerations. The principal scientific questions are whether tumors
      detected by screening are clinically significant, whether screening generates too
      many false-positive results, and whether early detection lowers morbidity or
      mortality. Both screening and treatment of prostate cancer can be harmful, making
      the tradeoff between benefits and risks especially relevant. Studies suggest that
      this judgment is highly personal, depending on the relative importance that
      individuals assign to potential outcomes. Opinions and policy considerations also
      influence views about the appropriateness of screening. Chief among these are
      personal beliefs about benefits and harms, medicolegal concerns, patient
      expectations, resource constraints, and opportunity costs. Appropriate policy
      must discriminate between what is best for populations and for individual
      patients. The lack of evidence of benefit and the potential harms argue against a
      societal policy of routine screening. Individual patients who could benefit from
      screening should be informed about the potential benefits and harms and invited
      to make a personal choice based on their priorities and concerns.

PMID- 10073274
TI  - Coagulase-negative staphylococci: role as pathogens.
AB  - Coagulase-negative staphylococci have long been regarded as apathogenic but their
      important role as pathogens and their increasing incidence have been recognized
      and studied in recent years. Although specific virulence factors are not as
      clearly established as they are in Staphylococcus aureus, it seems clear that
      factors such as bacterial polysaccharide components are involved in attachment
      and/or persistence of bacteria on foreign materials. Coagulase-negative
      staphylococci are by far the most common cause of bacteremia related to
      indwelling devices. Most of these infections are hospital-acquired, and studies
      over the past several years suggest that they are often caused by strains that
      are transmitted among hospitalized patients. Other important infections due to
      coagulase-negative staphylococci include central nervous system shunt infections,
      native or prosthetic valve endocarditis, urinary tract infections, and
      endophthalmitis. Intravenous treatment of systemic infections is usually required
      because coagulase-negative staphylococci have become increasingly resistant to
      multiple antibiotics.

PMID- 10073275
TI  - Bisphosphonates in the treatment of malignant bone disease.
AB  - Tumor-induced osteolysis or lytic bone disease is mediated by osteoclast
      activation. Osteoclasts can be activated directly by products produced by tumors
      or indirectly through other nonmalignant cells. By reducing osteoclastic
      activity, bisphosphonates inhibit bone resorption. Since these agents were shown
      effective in treating other diseases associated with increased bone resorption,
      including cancer-related hypercalcemia and Paget's disease of bone, studies have
      been initiated to explore the use of bisphosphonates in patients with osteolytic
      bone metastases. Recent large randomized double-blind studies show the efficacy
      of these agents in reducing skeletal complications in patients with bone
      metastases from both breast cancer and multiple myeloma.

PMID- 10073276
TI  - Insights from the study of heart rate variability.
AB  - Indices of heart rate variability (HRV) provide a window onto autonomic
      modulation of the heart. HRV indices, determined in either the time or frequency
      domain, are closely related and reflect parasympathetic, mixed sympathetic, and
      parasympathetic and circadian rhythms. In population studies, decreased HRV has
      had predictive value for mortality among healthy adults. It is a well-established
      risk factor for arrhythmic events and mortality among post-myocardial-infarction
      patients but has only moderate sensitivity and specificity. Decreased HRV has had
      mixed predictive success in congestive heart failure. Reduced HRV identifies
      diabetic patients with autonomic neuropathy. HRV in combination with other risk
      stratifiers, e.g. ejection fraction, can identify cardiac patients at especially
      high risk of mortality. Many but not all interventions associated with increased
      HRV are also associated with better survival rates.

PMID- 10073277
TI  - Hereditary peripheral neuropathies: clinical forms, genetics, and molecular
      mechanisms.
AB  - Hereditary peripheral neuropathies, among the most common genetic disorders in
      humans, are a complex, clinically and genetically heterogeneous group of
      disorders that produce progressive deterioration of the peripheral nerves. This
      group of disorders includes hereditary neuropathy with liability to pressure
      palsies, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and congenital
      hypomyelinating neuropathy. Our understanding of these disorders has progressed
      from the description of the clinical phenotypes and delineation of the
      electrophysiologic and pathologic features to the identification of disease genes
      and elucidation of the underlying molecular mechanisms.

PMID- 10073278
TI  - Applications of NMR spectroscopy to study muscle glycogen metabolism in man.
AB  - Prior to the advent of nuclear magnetic resonance (NMR) spectroscopy, human
      glucose metabolism was studied through tracer and tissue biopsy methodology. NMR
      spectroscopy now provides a noninvasive means to monitor metabolic flux and
      intracellular metabolite concentrations continuously. 13C NMR spectroscopy has
      shown that muscle glycogen synthesis accounts for the majority of insulin
      stimulated muscle glucose uptake in normal volunteers and that defects in this
      process are chiefly responsible for insulin resistance in type 1 and type 2
      diabetes mellitus, as well as in other insulin resistant states (obesity, insulin
      resistant offspring of type 2 diabetic parents, elevation of plasma FFA
      concentrations). Furthermore, using 31P NMR spectroscopy to measure intracellular
      glucose-6-phosphate, it has been shown that defects in insulin-stimulated glucose
      transport/phosphorylation activity are primarily responsible for the insulin
      resistance in these states.

PMID- 10073279
TI  - Immunologic therapy of multiple sclerosis.
AB  - Three interferon beta preparations (Betaseron, Avonex, and Rebif) have shown
      efficacy in the treatment of relapsing-remitting multiple sclerosis (MS). Attack
      frequency is reduced by 30% and major attacks to an even greater extent.
      Accumulating disease burden as measured by annual T2-weighted magnetic resonance
      imaging is markedly lessened, and disease activity as measured by serial
      gadolinium-enhanced MRI scanning is reduced by over 80%. A fourth preparation,
      Copaxone, a basic copolymer of four amino acids, lessens MS attack frequency by
      30% and also lessens disease activity as measured by gadolinium-enhanced MRI.
      Betaseron lessens accumulation of disability in MS patients with secondary
      progressive disease regardless of the severity of disability at the time
      treatment is commenced. MS is now a treatable disease.

PMID- 10073280
TI  - Allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients
      with asthma and cystic fibrosis. It is characterized by chronic colonization of
      the airways with a ubiquitous fungus, Aspergillus fumigatus. The clinical
      expression of ABPA results from the complex interaction of chronic colonization
      of the airways with A fumigatus, host factors allowing this colonization, and the
      host's genetically determined immune response. Clinically the syndrome is
      characterized by recurrent episodes of wheezing, mucus production, pulmonary
      infiltrates, and elevated levels of serum IgE. Many patients develop central
      bronchiectasis, and a subset will go on to endstage fibrotic lung disease. It is
      thought that treatment will prevent this progression. The mainstay of therapy
      remains oral corticosteroids.

PMID- 10073281
TI  - Postural hypotension: causes, clinical features, investigation, and management.
AB  - Postural hypotension may result from various neurogenic and non-neurogenic
      causes. It may be a key feature of certain disorders, such as the primary chronic
      autonomic failure syndromes; it can complicate a variety of diseases, such as
      diabetes mellitus; and its prevalence increases with advancing age. When
      symptomatic, it may result in loss of consciousness and thus cause injury.
      Postural hypotension can be suspected from the patient's history and is readily
      documented in the clinic by measuring lying and standing blood pressure. The
      diagnosis ideally should be confirmed in the laboratory with additional tests to
      determine the cause and evaluate the functional deficit, so as to aid treatment.
      Treatment of the causative disorder is often curative when there are non
      neurogenic causes. A combination of nonpharmacological and pharmacological
      measures is needed in the management of neurogenic postural hypotension.

PMID- 10073282
TI  - New transfusion strategies: red cell substitutes.
AB  - Red cell substitutes are solutions that can potentially be used in emergencies or
      during surgery when rapid expansion of the blood volume with an oxygen carrier is
      needed. The three main types of products in development are based on cell-free
      hemoglobin, perfluorocarbon emulsions, or liposome-encapsulated hemoglobin. None
      is currently approved for clinical use, but several are in advanced clinical
      trials. Outside the red blood cell, hemoglobin is subject to degradation and heme
      loss. It readily diffuses in the plasma space and effectively scavenges nitric
      oxide. These properties must be understood and controlled if hemoglobin-based
      products are to fulfill their promise. The development of red cell substitutes
      affords us a deeper insight into how oxygen is delivered to tissues in the
      microcirculation and how blood-flow distribution is regulated within and between
      organs. As red cell substitutes become available to clinicians and scientists,
      clinical applications are expected to expand.

PMID- 10073283
TI  - Escherichia coli O157:H7 gastroenteritis and the hemolytic uremic syndrome: an
      emerging infectious disease.
AB  - Escherichia coli O157:H7 is an increasingly common cause of a variety of
      illnesses, including bloody diarrhea and the hemolytic uremic syndrome. This
      emerging infectious agent was first identified in 1982 and has been isolated with
      increasing frequency since then. This chapter reviews the epidemiology, clinical
      spectrum, diagnosis, treatment, and prevention of infections with E. coli
      O157:H7.

PMID- 10073284
TI  - The graft-versus-leukemia effects of allogeneic cell therapy.
AB  - Until recently, the only cure for relapse after allogeneic bone marrow
      transplantation (BMT) has been a second BMT. Recently, infusions of leukocytes
      collected from the original transplant donor have been used to induce a direct
      graft-versus-leukemia (GVL) reaction in patients with relapsed disease. Adoptive
      immunotherapy with donor leukocyte infusions (DLI) results in complete remission
      for 60-80% of patients with relapsed chronic-phase CML; therapy is also effective
      for relapse of diseases other than CML, although response rates are lower.
      Adoptive immunotherapy induces remissions for the majority of patients with post
      transplantation Epstein-Barr virus-related lymphomas and other viral-associated
      illnesses. The extraordinary success of DLI demonstrates that it is now possible
      to harness the GVL potential of the human immune system for clinical benefit. The
      necessary effector cells and target antigens required for GVL reactivity are
      poorly defined but are the subject of intensive investigation. Future trials will
      investigate strategies that retain and enhance the GVL effects while limiting
      toxicity from this therapy, and they may define methods of successful allogeneic
      adoptive immunotherapy outside the setting of allogeneic BMT.

PMID- 10073285
TI  - Sleep and its disorders.
AB  - Sleep disorders are very prevalent in the general population and are associated
      with significant medical, psychological, and social disturbances. Insomnia is the
      most common. When chronic, it usually reflects psychological/behavioral
      disturbances. Most insomniacs can be evaluated in an office setting, and a
      multidimensional approach is recommended, including sleep hygiene measures,
      psychotherapy, and medication. The parasomnias, including sleepwalking, night
      terrors, and nightmares, have benign implications in childhood but often reflect
      psychopathology or significant stress in adolescents and adults and organicity in
      the elderly. Excessive daytime sleepiness is typically the most frequent
      complaint and often reflects organic dysfunction. Narcolepsy and idiopathic
      hypersomnia are chronic brain disorders with an onset at a young age, whereas
      sleep apnea is more common in middle age and is associated with obesity and
      cardiovascular problems. Therapeutic naps, medications, and supportive therapy
      are recommended for narcolepsy and hypersomnia; continuous positive airway
      pressure, weight loss, surgery, and oral devices are the common treatments for
      sleep apnea.

PMID- 10073286
TI  - The prognostic significance of altered cyclin-dependent kinase inhibitors in
      human cancer.
AB  - Progression through the cell cycle is governed by cyclin-dependent kinases
      (cdks), whose activity is inhibited by the cdk inhibitors. Cyclins, cdks, and cdk
      inhibitors are frequently deregulated in cancers. This chapter reviews the
      prognostic significance of alterations in cdk inhibitors. Loss of p27 protein
      provides independent prognostic information in breast, prostate, colon, and
      gastric carcinomas, and immunohistochemical (IHC) staining for p27 may eventually
      become part of routine histopathologic processing of cancers. Loss of IHC
      staining for p21 may be prognostic in certain cancers but conflicting results are
      reported in breast cancer. Reports on homozygous deletion of p16 and p15 genes
      suggest the value of larger, prospective studies with standardized treatment
      protocols to definitively establish the prognostic utility of p15/p16 deletions
      in acute leukemias. Larger trials and the development of a consensus on methods
      for deletion analysis, IHC staining, and tumor scoring will be needed to move
      these molecular assays from bench to bedside.

PMID- 10073287
TI  - Chemokines and chemokine receptors: biology and clinical relevance in
      inflammation and AIDS.
AB  - Chemokines constitute a large family of chemotactic cytokines that act at G
      protein-coupled receptors to regulate diverse biological processes, including
      leukocyte trafficking, angiogenesis, hematopoiesis, and organogenesis. They are
      believed to be both beneficial in host defense against infectious agents and
      harmful in diseases marked by pathologic inflammation; however, actual clinical
      roles in these areas have not yet been established. Recently, unexpected ways
      have been discovered in which medically important pathogens, including HIV-1,
      exploit or subvert the chemokine system. These and other recent results suggest
      that targeting specific chemokines and chemokine receptors may have therapeutic
      utility in both inflammation and infectious disease.

PMID- 10073288
TI  - Arrhythmias in the athlete with congenital heart disease: guidelines for
      participation.
AB  - Advances in the diagnosis and early management of congenital heart disease in
      recent decades have led to increasing numbers of individuals being sufficiently
      well to participate in social as well as truly competitive sports. Physicians are
      increasingly asked whether such participation is safe, advisable, and
      efficacious, yet few guidelines exist to help them make these decisions. There
      are three apparent subgroups of patients: (a) those with mild or repaired
      problems, who function normally or nearly so and may fully participate; (b) those
      with severe functional deficit or known high risk, for whom strenuous exertion
      must be strictly proscribed; and (c) those who fall in between, with some
      limitations and some risk--these patients present a great challenge to the wisdom
      and clinical skill of the physician.

PMID- 10073289
TI  - Natural history and preventative treatment of recurrent mood disorders.
AB  - This chapter focuses on recent developments in our understanding of the etiology,
      epidemiology, and treatment of recurrent mood disorders. It addresses the
      changing relationship between endogenous and exogenous factors over time in the
      etiology of mood episodes. In the area of epidemiology, the chapter presents new
      information on the prevalence of various subtypes and male/female differences in
      lifetime risk. Complications of the mood disorders, such as suicide, and
      important comorbidities, including alcoholism and substance abuse, are discussed.
      In the area of treatment, the life-long nature of many of the mood disorders is
      described, as is the consequent role of the primary care physician in their
      management. The evidence for the efficacy of the depression-specific
      psychotherapies, cognitive therapy and interpersonal therapy, is reviewed.
      Current issues in the pharmacotherapy of mood disorders are discussed, including
      the relative efficacy of the older antidepressants versus the newer selective
      serotonin reuptake inhibitors (SSRIs) and the treatment of various subtypes of
      mood disorders, including dysthymia, chronic depression, and atypical depression.
      Finally, the chapter describes recent advances in the treatment of bipolar
      disorder.

PMID- 10073290
TI  - Biology of gastroesophageal reflux disease: pathophysiology relating to medical
      and surgical treatment.
AB  - This chapter reviews the biology of gastroesophageal reflux disease, relating
      pathophysiology to medical and surgical therapy. Various definitions of the
      disease are presented and workable criteria are developed to identify patients
      with the disease. The central importance of the lower esophageal high-pressure
      zone as a barrier to reflux is emphasized, along with an analysis of its
      biomechanical alteration in disease. The composition of the refluxed gastric
      juice is characterized in regard to its potential for mucosal injury. Evidence is
      provided that cardiac-type mucosa is an acquired sequel to acid-induced squamous
      mucosal injury in the terminal esophagus. A hypothesis regarding the process of
      intestinalization of cardiac-type mucosa to form Barrett's esophagus is
      presented. An integrated concept of the pathophysiology of gastroesophageal
      reflux disease is constructed. Practical concepts regarding the treatment of
      gastroesophageal reflux disease are developed, based on a review of studies on
      the natural history of the disease and the long-term outcome of therapy.

PMID- 10073291
TI  - Dendritic cell vaccines for cancer immunotherapy.
AB  - Human tumors express a number of protein antigens that can be recognized by T
      cells, thus providing potential targets for cancer immunotherapy. Dendritic cells
      (DCs) are rare leukocytes that are uniquely potent in their ability to present
      antigens to T cells, and this property has prompted their recent application to
      therapeutic cancer vaccines. Isolated DCs loaded with tumor antigen ex vivo and
      administered as a cellular vaccine have been found to induce protective and
      therapeutic anti-tumor immunity in experimental animals. In pilot clinical trials
      of DC vaccination for patients with non-Hodgkin's lymphoma and melanoma,
      induction of anti-tumor immune responses and tumor regressions have been
      observed. Additional trials of DC vaccination for a variety of human cancers are
      under way, and methods for targeting tumor antigens to DCs in vivo are also being
      explored. Exploitation of the antigen-presenting properties of DCs thus offers
      promise for the development of effective cancer immunotherapies.

PMID- 10073292
TI  - Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and
      hantavirus pulmonary syndrome.
AB  - Hantaviruses chronically infect rodents without apparent disease, but when they
      are spread by aerosolized excreta to humans, two major clinical syndromes result:
      hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome
      (HPS). Both diseases appear to be immunopathologic, and inflammatory mediators
      are important in causing the clinical manifestations. In HPS, T cells act on
      heavily infected pulmonary endothelium, and it is suspected that gamma interferon
      and tumor necrosis factor are major agents of a reversible increase in vascular
      permeability that leads to severe, noncardiogenic pulmonary edema. HFRS has
      prominent systemic manifestations. The retroperitoneum is a major site of
      vascular leak and the kidneys suffer tubular necrosis. Both syndromes are
      accompanied by myocardial depression and hypotension or shock. HFRS is primarily
      a Eurasian disease, whereas HPS appears to be confined to the Americas; these
      geographic distinctions correlate with the phylogenies of the rodent hosts and
      the viruses that coevolved with them.

PMID- 10073294
TI  - Incidence and risk factors for ectopic pregnancy.

PMID- 10073295
TI  - Diagnosis of acute and persistent ectopic pregnancy.

PMID- 10073296
TI  - Medical management of ectopic pregnancy.

PMID- 10073297
TI  - Surgical management of ectopic pregnancy.
AB  - Laparoscopic salpingostomy remains the definitive and universal treatment of
      ectopic pregnancy in patients who are hemodynamically stable and who wish to
      preserve their fertility. The reproductive performance after salpingostomy
      appears to be equivalent or better than salpingectomy, but the recurrent ectopic
      pregnancy rate may be slightly greater. Expectant management has a poor efficacy
      and unproven benefit in subsequent reproductive outcome. Its use should be
      limited to situations in which the ectopic pregnancy is suspected but cannot be
      detected by transvaginal ultrasound. Methotrexate is an alternative to surgical
      treatment in selected patients who fulfill strict inclusion criteria, including
      compliance with follow-up evaluation. A large, prospective, randomized trial with
      significant power is needed, however, to study the prognostic factors for
      methotrexate success. The most practical and efficient method of methotrexate
      administration is a single intramuscular injection. Those who do not meet the
      criteria for methotrexate therapy should be treated surgically, which can be done
      by laparoscopy. Interstitial pregnancy also can be treated with methotrexate.
      Otherwise, a cornual resection or salpingotomy can be done. Although, it is
      feasible by laparoscopy, the laparoscopic approach should be done only by those
      who have an expertise in laparoscopic suturing. Abdominal and ovarian pregnancies
      are best treated surgically. Further, the diagnosis usually is established by
      laparoscopy, and an appropriate surgical treatment can be conducted at the same
      time.

PMID- 10073298
TI  - Ultrasound-guided injection of ectopic pregnancy.
AB  - Preliminary studies have demonstrated that salpingocentesis is a safe and
      effective treatment for unruptured ectopic pregnancies that are visible by
      transvaginal ultrasound. So far, experience with this technique has been confined
      to only a few centers around the world. The most promising results of these
      studies has been the virtual absence of side effects associated with local
      injection of either methotrexate or hyperosmolar glucose. Large prospective
      trials comparing efficacy, safety, and overall cost of salpingocentesis against
      systemic methotrexate will be necessary to better define the role of
      salpingocentesis in the management of ectopic pregnancy. Patient recruitment for
      this type of clinical trial would be feasible and acceptable to patients because
      both treatment arms would avoid surgery.

PMID- 10073299
TI  - Expectant management of ectopic pregnancy.

PMID- 10073301
TI  - Diagnosis of perinatal TORCH infections.
AB  - Collectively, TORCH infections create more neonatal morbidity than early-onset
      group B streptococcal sepsis. Fortunately, the incidence of maternal infection by
      CMV or toxoplasmosis is low (2-10 per 1,000 births). There have been tremendous
      advances in direct antigen testing and in the sensitivity and specificity of IgG
      and IgM testing. Consistently, research laboratories show more accurate results
      than in the past. Unfortunately, commercial laboratories are using older, single
      kit testing. The relatively poor degree of reliability can lead to unnecessary
      obstetric intervention or elective termination. Any positive pathogen-specific
      IgM on maternal serum should have additional confirmatory testing in a reputable
      research laboratory before any intervention. Direct antigen testing or multiple
      testing would seem to be appropriate for confirmation. This may include
      amniocentesis of fetal blood sampling. The research on the newer tests is based
      of the evaluation of blood from seriously immunocompromised subjects.
      Extrapolations of test accuracy to similar tests on healthy, pregnant women and
      their fetuses are likely to be in error. The application of these accurate tests
      to the obstetric population is a critical research need.

PMID- 10073302
TI  - Ultrasound and fetal diagnosis of perinatal infection.
AB  - Prenatal ultrasound can aid the clinician in evaluation of the patient with a
      suspected in utero TORCH infection, particularly toxoplasmosis, syphilis, and
      CMV. Demonstration of characteristic ultrasound findings in the high risk patient
      has a high predictive value for fetal infection and also may have prognostic
      significance. The sonologist should understand the limitations of ultrasound,
      discuss them with the patient, and document the discussion in the medical record.
      Patients should be counseled that ultrasound is not a sensitive test for fetal
      infection and that a normal fetal anatomy survey cannot predict a favorable
      outcome. In the low-risk patient, fetal infection should be considered when
      multiple organ system anomalies, fetal growth restriction, placental enlargement,
      or abnormalities of amniotic fluid volume are demonstrated.

PMID- 10073303
TI  - Perinatal cytomegalovirus and toxoplasmosis: challenges of antepartum therapy.

PMID- 10073304
TI  - Syphilis in pregnancy.

PMID- 10073305
TI  - Parvovirus infection.

PMID- 10073306
TI  - Perinatal consequences of hepatitis C.

PMID- 10073307
TI  - Prevention of perinatal herpes: prophylactic antiviral therapy?
AB  - So what is the take-home message from these studies? The first question, about
      fetal and neonatal safety, appears to be answered positively. With more than
      1,812 infants reported to have been exposed to varying amounts and duration of
      maternal acyclovir suppression, there has not been any apparent, short-term
      adverse fetal or neonatal effect. Use of acyclovir in infants, even in those that
      are premature, is very well tolerated, with a wide margin of safety. In addition,
      the pharmacokinetics studies by Frenkel et al and Kimberlin et al, as well as the
      animal studies, suggest that maternal use of acyclovir may actually provide a
      prophylactic and therapeutic benefit to an infant who is exposed to HSV. The
      second question, as to whether acyclovir suppression would simply change
      symptomatic outbreaks into asymptomatic ones, also appears to have some answers.
      The information provided by Wald et al indicated that acyclovir suppression
      actually decreases asymptomatic shedding, along with decreasing clinical
      recurrences. Because asymptomatic shedding seems to be similar in pregnant and
      nonpregnant patients, it would be reasonable to assume that asymptomatic shedding
      also would be decreased at delivery in pregnant women with HSV infection. This
      supposition is supported by the data from the randomized trials and cohort
      studies that demonstrated a lower than expected asymptomatic shedding rate. As
      yet, however, there has been no randomized trial in pregnant women that has had
      an adequate sample size to confirm this on a statistically significant basis. The
      third question, whether acyclovir suppression would lower the frequency of
      symptomatic recurrences at parturition, reducing the need for cesarean in these
      patients, has answers as well, although they may not be as clear cut as one would
      like. Women who experience their first genital herpes outbreak while they are
      pregnant seem to benefit from acyclovir suppression, with both a decrease in the
      risk of clinical recurrences at delivery and a decreased need for cesarean
      delivery. This is well documented by a randomized trial and other cohort studies.
      Acyclovir's efficacy in patients who have a history of genital herpes infections
      antedating their pregnancy is less clear. The data appear to indicate a
      clinically important decrease in the likelihood of symptomatic reactivations at
      the time of delivery, although the sample sizes in the randomized studies have
      been too small to draw a statistically significant conclusion one way or the
      other. Unfortunately, a definitive trial for this group of women may never be
      done. Assuming a 13% recurrence risk at the time of delivery and a 50% decrease
      in recurrences with the use of acyclovir, 652 women would have to complete the
      study to achieve a power of 80%. Conducting the study at the largest, single
      institution, prenatal center in the United States, Scott et al were only able to
      enroll 222 women during a period of 6 years. Likewise, Brocklehurst et al
      terminated their trial early because of recruitment difficulties. They enrolled
      only 63 women during a period of 4 years using two different sites in the United
      Kingdom. Unless a multicenter trial is conducted or a meta-analysis performed on
      the available data, we will probably have to be content with the data as it now
      stands. With valacyclovir and famciclovir now available, it is unlikely that any
      further work will be done with acyclovir. Information from the valacyclovir
      trials, however, may reach statistical significance because of changes in the
      study design that will allow smaller sample sizes to reach adequate power.
      Famciclovir treatment holds promise because of its longer intracellular half
      life, but until concerns about potential mutagenicity are resolved and more
      information on its efficacy for suppressive therapy becomes available, it should
      not be considered for maternal suppressive therapy. Acyclovir appears to be
      effective, at least in some cohorts, and is probably safe for the fetus. (AB

PMID- 10073308
TI  - TORCH testing in HIV-infected women.
AB  - The issue of TORCH testing in pregnant women infected with the HIV virus remains
      confusing, even more so than it is in the non-HIV-infected gravida.
      Unfortunately, the data presented in this article make the recommendations of how
      to test for these various infections in pregnancy that much more difficult.
      Patients who are newly diagnosed as being HIV-infected and referred for prenatal
      care or who have not had TORCH testing probably should be tested. Thus, the
      prenatal patient with newly diagnosed HIV infection should be tested for T.
      gondii IgG antibodies. If positive for IgG antibodies, IgM antibodies should be
      obtained in an attempt to rule out acute T. gondii infection. Patients who test
      negative do not require any further testing until after the pregnancy unless they
      are severely immunocompromised and show signs and symptoms of toxoplasmosis.
      Antibodies (IgG) to CMV should be obtained in the HIV-infected gravida who is at
      high risk for CMV disease, i.e., patients with CD4+ T cell counts less than
      100/mm3. Unfortunately, the previously described problems with antibody detection
      make this testing less than ideal; thus, it is not routinely recommended in the
      HIV-infected pregnant patient who presents for prenatal care except for those at
      risk of disease reactivation. As for herpes simplex virus testing, there is no
      value in routinely testing patients prenatally for evidence of the disease.
      Finally, syphilis testing in the HIV-infected gravida is of major importance.
      Once tested, the patient who tests negative and who remains at risk for infection
      should probably be retested in the third trimester. Patients who are found to
      have the disease and who are treated need to be tested serially to rule out re
      infection or treatment failure.

PMID- 10073309
TI  - Is routine antenatal toxoplasmosis screening justified in the United States?
      Statistical considerations in the application of medical screening tests.

PMID- 10073310
TI  - Whirling disease: host specificity and interaction between the actinosporean
      stage of Myxobolus cerebralis and rainbow trout Oncorhynchus mykiss.
AB  - Scanning electron microscopic studies were conducted on rainbow trout
      Oncorhynchus mykiss in the first 60 min after their exposure to the
      triactinomyxon spores of Myxobolus cerebralis. The results demonstrated that as
      early as 1 min post exposure the whole process, from the attachment of the
      triactinomyxon spores to the complete penetration of their sporoplasm germs, had
      occurred. The triactinomyxon spores sought out the secretory openings of mucous
      cells of the epidermis, the respiratory epithelium and the buccal cavity of trout
      and used them as portals of entry. Exposure experiments of the triactinomyxon
      spores of M. cerebralis to non-salmonid fish, such as goldfish Carassius auratus,
      carp Cyprinus carpio, nose Chondrostoma nasus, medaka Oryzias latipes, guppy
      Poecilia reticulata and also the amphibian tadpole Rana pipiens as well as to
      rainbow trout fry indicated a specificity for salmonids. Attempts to activate the
      triactinomyxon spores by exposure to mucus prepared from cyprinid and salmonid
      fish showed no significant differences from those conducted in tap water. The
      results suggest that the simultaneous presence of both mechano- and chemotactic
      stimuli was required for finding the salmonid fish host.

PMID- 10073311
TI  - Rainbow trout leucocyte activity: influence on the ectoparasitic monogenean
      Gyrodactylus derjavini.
AB  - The ectoparasitic monogenean Gyrodactylus derjavini from rainbow trout
      Oncorhynchus mykiss was exposed in vitro to macrophages isolated as peritoneal
      exudate cells or as pronephros cells from the host. Cells colonized the parasite
      especially in the mannose-rich regions in the cephalic ducts where ciliated
      structures were abundant. Opsonization with fresh serum, in contrast to heat
      inactivated serum, enhanced colonization also on other body parts. The adverse
      effect of the activated macrophages towards G. derjavini was associated with a
      heat-labile component released from these cells to the culture medium. Analysis
      of substances released from the cells showed reactivity for a number of enzymes,
      complement factor C3, interleukin (Il-1) and reactive oxygen metabolites.
      Chemotaxis assays with pronephric leucocytes showed chemoattractants in G.
      derjavini, and the respiratory burst level of macrophages was slightly elevated
      due to parasite exposure. It is suggested that skin leucocytes contribute to an
      increased level of complement factors in the trout skin during the host response,
      whereby a hostile microenvironment for the parasites is created. In addition, the
      IL-1 production could affect mucous cell secretion and hyperplasia and add to the
      antiparasitic action of the epithelium. Likewise, reactive oxygen metabolites and
      various enzymes are likely to be involved in the skin response.

PMID- 10073312
TI  - Pathogenicity of Ichthyophonus hoferi for laboratory-reared Pacific herring
      Clupea pallasi and its early appearance in wild Puget Sound herring.
AB  - Laboratory-reared pathogen-free Pacific herring were exposed to pure cultures of
      Ichthyophonus hoferi, and reproduced the disease seen in naturally infected fish-
      thus fulfilling Koch's Postulates. Pathogen-free herring used in this study were
      reared from artificially spawned eggs incubated in filtered, UV-sterilized
      seawater, eliminating the variables associated with multiple infections, which
      are common in wild herring. Wild free-ranging herring were captured monthly from
      June through October by dip net from 'herring balls' located in the northern
      Puget Sound. I. hoferi infections were identified in these fish soon after
      metamorphoses, about 4 mo post-hatch. The prevalence increased from 5 to 6% in 0
      yr fish to 24% in 1-yr-old fish to 50 to 70% in fish over 2 yr old, with no
      associated increase in mortality. The route of natural transmission to wild
      herring was not determined, but carnivorous fish became infected and died when
      they were experimentally fed tissues infected with the organism. In vitro culture
      of tissues was the most sensitive method for identifying both clinical and
      subclinical infections.

PMID- 10073313
TI  - Natural mass infection by heterophyid metacercariae in aquacultured Japanese eel
      in Taiwan.
AB  - A natural mass infection of heterophyid metacercariae in aquacultured Japanese
      eel Anguilla japonica in Taiwan was observed. Of the 28,000 adult eels in 2
      ponds, about 25,000 (90%) showed swollen, cloudy and white eyes. Although
      morbidity was about 90%, there was no mortality among the affected eels.
      Histopathological sections showed edema and hemorrhage of the eye. Numerous
      metacercariae were observed in the muscle tissues around the eyeball, the
      subcutaneous tissue and even in the cartilage. Of the 6 eels digested with
      artificial gastric juice, all were found to contain metacercariae in their muscle
      tissues. The average number of metacercariae recovered from the 6 eels was 1219,
      with a range of 50 to 3762. These metacercariae, when fed orally to
      immunodeficient (scid) mice, developed into adult worms which were identified as
      Procerovum cheni Hsu 1950. The naturally infected eels were transferred to a new
      pond without snails and their eye lesions were not apparent anymore after 2 wk.
      In a follow-up investigation, 19 of 20 apparently healthy eels in a nearby
      aquaculture farm were found to harbour metacercariae in their muscles. However,
      the number of the metacercariae ranged from 1 to 14, with an average of 4.21.
      This is the first report of heterophyid metacercariae causing mass morbidity in
      aquacultured eels.

PMID- 10073314
TI  - Tumor-like lesions in the mantle of the mussel Modiolus difficilis from the Sea
      of Japan.
AB  - Two inner growths in the mantle beneath the epithelium were found in 1 of 1000
      mussels Modiolus difficilis from Amursky Bay, Sea of Japan, within the city
      precincts of Vladivostok. Both growths were about 2000 microns in maximal
      diameter in section and elevated slightly above the mantle surface. The mantle
      epithelium near the growths formed deep invaginations, and clusters of mucous
      cells were numerous beneath the epithelium. Histological and histochemical
      methods were employed. Two different kinds of growth were revealed. The off-white
      growth consisted of cells with thin granular or vesicular cytoplasm containing
      glucosaminoglycans, proteins and a small amount of neutral polysaccharides.
      Growth cells were pure white in color after treatment of preparations with 1%
      H2SO4 and differed markedly from the mantle cells. The yellow growth consisted of
      large granular cells with neutral polysaccharides and proteins. Although growths
      were composed of different kinds of cells, they seemed to be derived from
      subepithelial mucous cells. This was supported by histological and histochemical
      staining reactions of some tumor and mantle epithelial cells. Mitotic indices
      (MI) of growths and subepithelial mucous cells were zero, MI of ciliated mantle
      epithelium reached 0.07%. The lesions were areas of strongly altered mucous cells
      of mantle epithelium and were non-neoplastic.

PMID- 10073315
TI  - Nosema notabilis (Microsporidia), its ultrastructure and effect on the
      myxosporean host Ortholinea polymorpha.
AB  - Nosema notabilis Kudo, 1939 produces chain-forming meronts with a dense cell coat
      in direct contact with the host cell cytoplasm. Cytoplasmic microtubules and
      membranaceous whorls could be observed in meront cytoplasm. Sporonts differ in
      that they have a thicker cell wall and more conspicuous endoplasmic reticulum
      (ER) cisternae. Sporoblasts have an externally ridged cell wall. Spores have an
      apically located anchoring disc, an isofilar polar tube with 6 to 9 turns and
      polyribosomal strands in the sporoplasm. Diplokarya occur in all stages. Heavily
      infected plasmodia of Ortholinea polymorpha (Davis, 1917) reveal marked
      pathological signs. The most prominent are reduction of surface projections
      and/or pinocytosis, inflated mitochondria with altered inner structures, affected
      vegetative nuclei, damage to generative cells and occurrence of various anomalous
      formations in the plasmodium cytoplasm. The damage may result in complete
      disintegration of the plasmodium. However, the development of the microsporidian
      is affected by a remarkably high percentage of teratological stages revealing
      membranaceous and tubular structures.

PMID- 10073316
TI  - Isolation and characterization of Vibrio parahaemolyticus causing infection in
      Iberian toothcarp Aphanius iberus.
AB  - High mortality among laboratory cultured Iberian toothcarp Aphanius iberus
      occurred in February 1997 in Valencia (Spain). The main signs of the disease were
      external haemorrhage and tail rot. Bacteria isolated from internal organs of
      infected fish were biochemically homogeneous and identified as Vibrio
      parahaemolyticus. The bacteria were haemolytic against erythrocytes from eel
      Anguilla anguilla, amberjack Seriola dumerili, toothcarp A. iberus and humans,
      and were Kanagawa-phenomenon-negative. Infectivity tests showed that the
      virulence for A. iberus was dependent on salinity. Finally, all strains were
      virulent for amberjack and eel.

PMID- 10073317
TI  - Review and survey of the issues in asthma today.

PMID- 10073318
TI  - Pharmacologic therapy for asthma: overview and historical perspective.
AB  - For the 30 years between 1967 and 1997, pharmacologic therapy of asthma has
      consisted primarily of five classes of drugs, beta 2-agonists, anticholinergics,
      theophyllines, cromones, and corticosteroids. The first four of these classes of
      drugs have origins in herbal treatments going back 5000 or 6000 years. This
      article briefly reviews the history of asthma pharmacotherapy up to the late
      1990s and outlines a current approach to the pharmacotherapy of asthma, which is
      but one component of an integrated overall approach to asthma treatment involving
      patient education and environmental control as well.

PMID- 10073319
TI  - Asthma therapy from the practice perspective: changes in the wind.
AB  - The management of asthma presents a challenge to practicing primary care
      physicians, which is about to escalate considerably. First, it is becoming
      crystal clear that asthma is a heterogeneous condition that continues to be more
      prevalent in the community. This makes objective data (FEV1, PEFR, etc.) as
      essential as the care taken to work with patients so that they not only
      understand their disease but also how to properly use the medications they have
      been prescribed. Second, the number of new classes of agents will increase in the
      next decade far faster than an understanding of the asthmatic process, making it
      imperative for the physician to return to the basic principles of therapeutics.

PMID- 10073320
TI  - Are new asthma therapies needed?
AB  - For many years, effective therapy for the management of asthma has been
      available. Issues of adverse side effects and questionable patient compliance
      with current therapies have been seen as deterrents for proven beneficial agents
      such as the anti-inflammatory corticosteroids and the bronchodilating beta 2
      agonists. As effective as available agents are, the goal of consistent efficacy
      and ease of use has fueled research into new therapies that are either easier to
      use or have a more favorable side effect profile.

PMID- 10073321
TI  - Recent advances in our understanding of the use of theophylline in the treatment
      of asthma.
AB  - The use of theophylline for the treatment of asthma for 45 of the past 50 years
      has been for its ability to dilate bronchi. The problem has been that at the most
      effective bronchodilating dose, toxicity was too close for comfort. In the past 5
      years, there has been resurgence in theophylline use at lower doses because of
      some well-documented anti-inflammatory and steroid sparing effects.

PMID- 10073322
TI  - The role of the common cold in asthma.
AB  - It has long been known that patients with viral respiratory infections develop
      temporary asthma-like symptoms or see a worsening of their existing asthmatic
      symptoms or develop full-blown asthma during the infection. It should not be
      surprising, in view of this observation, that these same viruses have been found
      to initiate the same inflammatory processes as seen and characterized in the
      asthmatic patient. This has clear implications for therapy of asthmatic patients.

PMID- 10073323
TI  - Genetics of asthma: from chicken soup to Napoleon to Toronto.
AB  - For a number of reasons, genetics has always been thought to be involved in
      asthma. It is only now, with several approaches and tools to make population
      genetic studies possible, that studies are intensified. Using both the candidate
      gene and the positional cloning approaches, there is evidence that predisposing
      factors, if not the disease itself, are genetically transferred. In addition,
      studies on inbred island populations have further demonstrated a high probability
      of a genetically transferable link. If the genes can be identified, diagnostic
      tests or predictions regarding the response to specific therapy are advances that
      would follow.

PMID- 10073324
TI  - Effect of venlafaxine on CYP1A2-dependent pharmacokinetics and metabolism of
      caffeine.
AB  - Venlafaxine is a clinically effective antidepressant. Caffeine is a metabolic
      probe for the quantitative measurement of CYP1A2 activity in vivo. This open
      label study evaluated the effect of steady-state venlafaxine on CYP1A2-dependent
      metabolism, as measured by the pharmacokinetic disposition of caffeine, and
      urinary caffeine metabolite ratios (CMRs). Sixteen healthy subjects received 200
      mg of caffeine orally before (Day 1) and after (Day 8) venlafaxine was titrated
      to steady-state (37.5 mg every 12 hours on Days 2-4, then 75 mg every 12 hours on
      Days 5-8). Samples were collected before and for 24 hours after caffeine dosing
      for the determination of caffeine in plasma and 1,7-dimethylxanthine, 3,7
      dimethylxanthine, 1,7-dimethyluric acid (17U), 1-methylxanthine (1X) and 1
      methyluric acid (1U), and 5-acetylamino-6-amino-3-methyluracil (AAMU) in urine.
      Blood samples were obtained before venlafaxine doses on Days 7 and 8 (morning
      dose only) for the determination of trough venlafaxine and O-desmethylvenlafaxine
      levels. Venlafaxine did not significantly alter the pharmacokinetics of caffeine
      and its metabolites. Plasma caffeine AUC was unchanged and remained within the
      bioequivalence criteria (90% confidence interval: 87.9%-102%) in the presence of
      venlafaxine. Urine metabolite data showed variable increases and decreases in the
      CMR [(AAMU + 1U + 1X)/17U] for individual subjects. However, the mean CMR was
      altered by < 10% in the presence of venlafaxine. This in vivo study demonstrated
      that venlafaxine did not alter the pharmacokinetic profile of caffeine and
      confirms in vitro data that venlafaxine does not inhibit CYP1A2 metabolism.
      Therefore, venlafaxine appears to have a relatively low potential for drug
      interactions based on CYP1A2 inhibition.

PMID- 10073325
TI  - Hormonal effects on tirilazad clearance in women: assessment of the role of
      CYP3A.
AB  - This study assessed whether the previously reported difference in tirilazad
      clearance between pre- and postmenopausal women is reversed by hormone
      replacement and whether this observation can be explained by differences in
      CYP3A4 activity. Ten healthy women from each group were enrolled: premenopausal
      (ages 18-35), postmenopausal (ages 50-70), postmenopausal receiving estrogen, and
      postmenopausal women receiving estrogen and progestin. Volunteers received 0.0145
      mg/kg midazolam and 3.0 mg/kg tirilazad mesylate intravenously on separate days.
      Plasma tirilazad and midazolam were measured by HPLC/dual mass spectrophotometry
      (MS/MS) assays. Tirilazad clearance was significantly higher in premenopausal
      women (0.51 +/- 0.09 L/hr/kg) than in postmenopausal groups (0.34 +/- 0.07, 0.32
      +/- 0.06, and 0.36 +/- 0.08 L/hr/kg, respectively) (p = 0.0001). Midazolam
      clearance (0.64 +/- 0.12 L/hr/kg) was significantly higher in premenopausal women
      compared to postmenopausal groups (0.47 +/- 0.11, 0.49 +/- 0.11, and 0.53 +/-
      0.19 L/hr/kg, respectively) (p = 0.037). Tirilazad clearance was weakly
      correlated with midazolam clearance (r2 = 0.129, p = 0.02). Tirilazad clearance
      is faster in premenopausal women than in postmenopausal women, but the effect of
      menopause on clearance is not reversed by hormone replacement. Tirilazad
      clearance in these women is weakly related to midazolam clearance, a marker of
      CYP3A activity.

PMID- 10073326
TI  - Pharmacokinetics of trimetrexate and dapsone in AIDS patients with Pneumocystis
      carinii pneumonia.
AB  - The objective of this study was to determine the pharmacokinetics of trimetrexate
      and dapsone in AIDS patients with moderate to severe pneumocystis pneumonia.
      Trimetrexate, leucovorin, and dapsone were administered for 21 +/- 3 days in the
      following doses: trimetrexate glucuronate, 45 mg/m2; leucovorin, 20 mg/m2; and
      dapsone, 100 mg daily. The pharmacokinetics of trimetrexate, dapsone, and
      dapsone's metabolite, monoacetyldapsone, were determined at three separate
      periods over the course of treatment. Serial blood samples were obtained over 24
      hours after dosing and analyzed for trimetrexate, dapsone, and monoacetyldapsone,
      and pharmacokinetic parameters were determined. The mean parameters obtained for
      the early, mid-, and late collection periods were the following: trimetrexate:
      t1/2 = 8.29, 9.15, 10.00 hr; AUC = 16.85, 22.38, 24.49 mg.hr/l; CI = 5.58, 4.14,
      3.96 l/hr, respectively. DDS: t1/2 = 14.99, 16.59, 15.13 hr; AUC = 30.60, 35.29,
      36.08 mg.hr/l; CI = 3.82, 3.49, 3.01 l/hr, respectively. Monoacetyldapsone: t1/2
      = 20.25, 18.66, 16.32 hr; AUC = 24.05, 24.06, 23.86 mg.hr/l, respectively. No
      statistically significant changes in pharmacokinetics for trimetrexate or dapsone
      were observed over the 21 +/- 3 day course of treatment. The results suggest that
      there are no major interactions between trimetrexate and dapsone when
      administered together in acutely ill patients.

PMID- 10073327
TI  - Menstrual cycle variability in midazolam pharmacokinetics.
AB  - Activity of cytochrome P450 3A4 (CYP3A4), the most abundant human P450 isoform
      and responsible for metabolizing approximately half of all therapeutic agents,
      has been speculated to vary during the menstrual cycle. This investigation
      evaluated CYP3A4 activity during the menstrual cycle, using midazolam clearance
      as a metabolic probe. Midazolam (1 mg i.v.) was administered to nonsmoking,
      nonpregnant female volunteers (N = 11, age 26 +/- 5 years) with normal menstrual
      cycles on three separate occasions during the same cycle: days 2 (menstrual
      phase), 13 (estradiol peak), and 21 (progesterone peak). Venous plasma midazolam
      concentrations were determined by gas chromatography-mass spectrometry. Midazolam
      clearance was determined by noncompartmental and compartmental analysis.
      Midazolam plasma disposition did not differ between phases of the menstrual
      cycle. There was no significant difference in any measure of midazolam clearance.
      Noncompartmental clearances (mean +/- SD) were 7.36 +/- 2.73, 6.34 +/- 3.59, and
      6.23 +/- 2.04 ml/kg/min, respectively, on days 2, 13, and 21 of the menstrual
      cycle. These results suggest no difference in hepatic CYP3A4 activity on
      menstrual cycle days 2, 13, and 21. Consideration of menstrual cycle variability
      in the metabolism of CYP3A4 substrates does not appear indicated in the dosing or
      design of clinical trials.

PMID- 10073328
TI  - Open-label, single-dose pharmacokinetic study of modafinil tablets: influence of
      age and gender in normal subjects.
AB  - An open-label, single-center, single-dose, parallel-group study was performed in
      healthy young males and females as well as healthy elderly males to examine the
      influence of age and gender on the pharmacokinetics of modafinil following
      administration of a single 200 mg oral dose. Twelve subjects were enrolled in
      each of the following three groups: young males, young females, and elderly
      males. Each fasted (overnight) subject received 2 x 100 mg modafinil tablets.
      Blood and urine samples were collected at various times up to 72 hours postdose
      for the determination of plasma and urine levels of modafinil as well as the acid
      and sulfone metabolites. The plasma concentrations of the individual isomers, d-
      and l-modafinil, were also determined. Pharmacokinetic parameters were determined
      by noncompartmental methods. Modafinil was well tolerated at a single oral dose
      of 200 mg. The most commonly reported adverse events were headache, fever,
      pharyngitis, and asthenia. There were no clinically meaningful differences with
      respect to the incidence rate of treatment-emergent adverse events among the
      young female, young male, and old male groups. Modafinil was rapidly absorbed
      after oral dosing and slowly cleared (t1/2 approximately 11-14 hr) from the body.
      Modafinil acid was the major urinary metabolite, which accounted for 35% to 60%
      of the dose. Results from this study indicated that there were age and gender
      effects on modafinil clearance processes. In this regard, the clearance rate of
      modafinil in males decreased with age while young females cleared modafinil at a
      faster rate than young males. Stereospecific pharmacokinetics of modafinil were
      also demonstrated. The d-modafinil was eliminated three times faster than the l
      modafinil.

PMID- 10073329
TI  - Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation
      compared with immediate-release oxybutynin.
AB  - Oxybutynin is used for the treatment of urge urinary incontinence. In this
      randomized, open-label, two-way crossover, multiple-dose study, the
      pharmacokinetics of a once-daily, controlled-release formulation, OROS oxybutynin
      chloride, was compared with that of immediate-release (IR) oxybutynin (Ditropan).
      Thirteen healthy female volunteers received three 5 mg OROS oxybutynin chloride
      tablets once daily for 4 days or IR oxybutynin 5 mg administered every 8 hours
      for 4 days. On day 1, with OROS oxybutynin chloride, mean plasma concentrations
      rose slowly over approximately 6 hours following dosing (mean Cmax 4.2 ng/mL) and
      remained fairly constant over the 24-hour dosing interval, whereas with IR
      oxybutynin, mean plasma concentrations rose rapidly within the first hour after
      dosing (mean Cmax 12.0 ng/mL), then declined. The mean oxybutynin degree of
      fluctuation was much lower for OROS oxybutynin chloride (78%) than for IR
      oxybutynin (371%). For both formulations, the plasma concentration-time profiles
      for the metabolite N-desethyloxybutynin paralleled those of oxybutynin but at
      higher concentrations. Steady-state oxybutynin concentrations were achieved by
      day 3 for both formulations. Mean area under the concentration-time curve (AUC)
      values for both oxybutynin and its metabolite were similar between day 1 and day
      4 for each treatment, suggesting time-invariant pharmacokinetics. With OROS
      oxybutynin chloride, mean relative bioavailability was higher (153%) for
      oxybutynin and lower (69%) for N-desethyloxybutynin compared with IR oxybutynin.
      This increased bioavailability may be due to reduced first-pass metabolism;
      within 3 to 5 hours after dosing, OROS systems are thought to reach the colon,
      where cytochrome P450-mediated oxidation (oxybutynin's primary metabolic pathway)
      may be less extensive than in the small intestine. Fewer subjects reported any
      adverse event with OROS oxybutynin chloride than with IR oxybutynin (including
      dry mouth, oxybutynin's most frequently reported anticholinergic adverse effect).

PMID- 10073330
TI  - Effect of venlafaxine on the pharmacokinetics of risperidone.
AB  - An open-label study evaluated the effect of steady-state venlafaxine on the
      single-dose pharmacokinetic profile of risperidone, a CYP2D6 substrate; its
      active metabolite, 9-hydroxyrisperidone; and the total active moiety (risperidone
      plus 9-hydroxyrisperidone). Thirty healthy subjects received a 1 mg oral dose of
      risperidone before and after venlafaxine dosing to steady state. No significant
      changes occurred between treatments in the area under the concentration-time
      curve (AUC) for 9-hydroxyrisperidone or the total active moiety. However,
      venlafaxine weakly altered the pharmacokinetics of risperidone. Oral clearance
      decreased 38%, and the volume of distribution decreased 17%, resulting in a 32%
      increase in the AUC for risperidone. Renal clearance of 9-hydroxyrisperidone also
      decreased by 20% in the presence of venlafaxine. Safety profiles of both drugs
      were not altered. This study demonstrated that venlafaxine did not affect the
      pharmacokinetic profile of 9-hydroxyrisperidone or the total active moiety,
      although it weakly inhibited the metabolism of risperidone. These results show
      that venlafaxine is unlikely to be involved in a pharmacokinetic interaction with
      concomitant risperidone.

PMID- 10073331
TI  - Case report: rhabdomyolysis induced by mibefradil in a patient treated with
      cyclosporine and simvastatin.

PMID- 10073332
TI  - Recent progress in the neurotoxicology of natural drugs associated with
      dependence or addiction, their endogenous agonists and receptors.
AB  - Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine
      in opium are well known as drugs associated with dependence or addiction.
      Endogenous active substances that mimic the effects of the natural drugs and
      their respective receptors have been found in the mammalian central nervous
      system (CNS). Such active substances and receptors include acetylcholine (ACh)
      and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta
      9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine,
      respectively. Considerable progress has been made in studies on neurotoxicity, in
      terms of the habituation, dependence and withdrawal phenomena associated with
      these drugs and with respect to correlations with endogenous active substances
      and their receptors. In this article we shall review recent findings related to
      the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients,
      nicotine, delta 9-THC and morphine in relation to their respective endogenous
      agents and receptors in the CNS.

PMID- 10073333
TI  - A novel quantitative morphometry of germ cells for the histopathological
      evaluation of rat testicular toxicity.
AB  - A view that 14 stages of rat spermatogenic cycle could be arranged into 4 groups,
      viz., conventional stages I-VI, VII-VIII, IX-XI and XII-XIV, according to the
      features of elongated spermatids was previously presented. A novel morphometry of
      seminiferous epithelia based on these 4 groups was also proposed. In the present
      study, utility of the proposed morphometry in the histopathological evaluations
      of testicular toxicities was monitored in comparison with the conventional one.
      After administrating adriamycin, ethylene glycol monomethyl ether or 1,3
      dinitrobenzene to rats, the viability of their germ cells was estimated by the
      proposed morphometry and the conventional one employed stages II-III, V, VII, X
      and XII. In every case, the evaluating results of the proposed morphometry were
      similar to those of the conventional one. Thus, it was verified that the proposed
      morphometry was identical with the conventional one in respect of reliable
      detection of the testicular toxicities. In addition, in situ terminal dUTP nick
      end labeling indicated that death of spermatogonia, pachytene spermatocytes or
      round spermatids induced by the above 3 toxic compounds was exclusively apoptotic
      death. In conclusion, the proposed morphometry would be useful as a practical
      tool in the evaluation of testicular toxicities.

PMID- 10073334
TI  - Lack of inhibitory effects of the Ju-myo protein on development of glutathione S
      transferase placental form-positive foci in the male F344 rat liver.
AB  - The effects of the 77 kDa Ju-myo protein, isolated from Drosophila melanogaster,
      on the development of glutathione S-transferase placental form (GST-P) positive
      foci in the male F344 rat liver were evaluated using a medium-term bioassay
      system. No modifying potential was evident in terms of the numbers or areas of
      GST-P positive foci. Ju-myo protein did not exert any influence on cell
      proliferation, as reflected by ornithine decarboxylase (ODC) or
      spermidine/spermine N1-acetyltransferase (SAT) activity and BrdU labeling. These
      results demonstrated that Ju-myo protein is unlikely to have inhibitory or
      promoting effects on rat liver carcinogenesis.

PMID- 10073335
TI  - A three-month repeated oral administration study of a low viscosity grade of
      hydroxypropyl methylcellulose in rats.
AB  - The toxicity of the lowest viscosity grade of hydroxypropyl methylcellulose
      (HPMC) that is currently commercially available was investigated by means of a
      three-month repeated oral administration study in male and female Crj:CD (SD) IGS
      rats at doses of 505, 1,020 and 2,100 mg/kg/day. Body weights of males and
      females in the 2,100 mg/kg group were lower than those of the control group on
      and after day 28 of administration, but the differences were not statistically
      significant. The degree of suppression of body weight gain in males was higher
      than that in females. This tendency was similar to the results in other toxicity
      studies of HPMC that have been reported. Males in the 2,100 mg/kg group showed a
      tendency (not significant) for decreased food consumption and urine volume.
      Examinations of general signs, hematology, blood chemistry, ophthalmology,
      absolute and relative organ weights, autopsy and histopathology revealed only a
      few, apparently coincidental, statistically significant differences from the
      control, and no evidence of any dose-dependent changes was found. It was
      concluded that the lowest viscosity grade of HPMC showed extremely low toxicity
      under the conditions of this study, as has been found for higher viscosity
      grades.

PMID- 10073336
TI  - Mechanism of weight gain suppressing effect of ER-40133, an angiotensin I
      converting enzyme inhibitor, in growing rats.
AB  - Effects of ER-40133, an inhibitor of angiotensin converting enzyme (ACE), on
      weight gain and sodium and potassium balance were studied in growing SD male
      rats. Thirty-two animals (seven weeks of age) were divided into two groups; one
      received a standard diet containing 0.227% sodium and the other a low (0.065%)
      sodium diet. They were divided into four subgroups; one control group and three
      treated groups receiving 3, 10 or 30 mg/kg of ER-40133, by gavage, once a day for
      five consecutive days. Body weight gain (average of the standard and low sodium
      diet groups) was -32% in the 3 mg/kg group,-74% in 10 mg/kg group and -99% in 30
      mg/kg group, when compared with the control group. There was a highly linear
      correlation between suppression of body weight gain and reduction in sodium and
      potassium retention for both groups of animals given the standard and low sodium
      diet. The reduced sodium retention, the primary effect of ACE inhibitors,
      accounted for about 30% of suppressed weight gain, and the reduced potassium
      retention, the secondary effect of sodium deficiency, could account for the rest
      about 70% of weight suppression by ER-40133.

PMID- 10073337
TI  - Does nicotine modify the psychotoxic effect of methamphetamine? Assessment in
      terms of locomotor sensitization in mice.
AB  - In this study, effects of nicotine on locomotor sensitization to methamphetamine
      in mice were investigated to assess whether nicotine modified induction and
      expression of psychotoxic action of methamphetamine. Although nicotine (0.03-1
      mg/kg s.c.) had no effect at first administration, 5-time nicotine
      administrations at 3-day intervals progressively developed a significant
      locomotor stimulant effect, and caused an enhanced sensitivity (cross
      sensitization) to methamphetamine (2 mg/kg s.c.). Five-time administrations of
      methamphetamine (2 mg/kg) at 3-day intervals produced not only a locomotor
      sensitization to methamphetamine itself, but also a cross-sensitization to
      nicotine (0.1-1 mg/kg). Nicotine (0.03-1 mg/kg) did not affect the locomotor
      stimulant effect of methamphetamine (2 mg/kg) in the drug-naive mice. However,
      nicotine acted dose-dependently to reduce the progressive enhancement of the
      locomotor stimulant effect of methamphetamine during 5-time repeated
      administrations. Mice treated with coadministration of methamphetamine with
      nicotine (1 mg/kg) showed less sensitization to methamphetamine than mice treated
      with methamphetamine alone. In addition, nicotine (1 mg/kg) inhibited the
      locomotor stimulant effect of methamphetamine in mice sensitized to
      methamphetamine. These results suggest that methamphetamine and nicotine produce
      a symmetrical cross-sensitization, although nicotine may act to inhibit the
      induction and expression of locomotor sensitization to methamphetamine in mice.

PMID- 10073338
TI  - Sperm abnormalities and histopathological changes in the testes in Crj:CD(SD)IGS
      rats.
AB  - In this study, morphological examination and computer-assisted sperm analysis
      (CASA) of epididymal spermatozoa in non-treated Crj:CD(SD)IGS rats were
      performed, and the relationship between the data obtained and the retention of
      step 19 spermatids in Stage IX to XI seminiferous tubules was examined. Retention
      of step 19 spermatids in Stage IX to XI seminiferous tubules was observed in all
      50 untreated males, and the incidence ranged from 3.3% to 100%. Eighteen animals
      showed a high incidence of retention (74.7 +/- 14.2%, HIR for short), and the
      others showed a low incidence (24.9 +/- 11.0%, LIR for short). Although the
      incidence of retention in Stage X and XI seminiferous tubules was very low in LIR
      males, it was high in HIR males (1.8 +/- 3.0% vs 58.6 +/- 23.2%). Morphological
      abnormalities of sperms in the caudal region of the epididymis, mainly amorphous
      head and no head, were more frequently observed in HIR males than in LIR males
      (36.2 +/- 28.5% vs 1.8 +/- 1.2%). Sperm analysis also revealed some differences
      between HIR and LIR males: sperm motility in HIR males was severely lower than
      that in LIR males, and sperm velocity, beat/cross frequency and amplitude of
      lateral head displacement in HIR males were lower than the corresponding values
      in LIR males. In summation, retention of step 19 spermatids frequently occurred
      in the non-treated Crj:CD(SD)IGS males, and a relationship between the retention
      of these spermatids and sperm abnormalities, such as morphologically abnormal
      sperms, low motility and other items revealed by sperm analysis (CASA), was
      suggested.

PMID- 10073339
TI  - NO contribution to lipopolysaccharide-induced hepatic damage in galactosamine
      sensitized mice.
AB  - To investigate the role of nitric oxide (NO) in hepatitis-induced endotoxemia, we
      injected mice intraperitoneally with 250 mg/kg galactosamine (GalN) and 1 mg/kg
      lipopolysaccharide (LPS) separately and in combination. NO synthesis increased in
      a dose-dependent manner with LPS. NO generation at 5 hr after administration of
      LPS was greater than that at 24 hr. Enhancement of NO generation was demonstrated
      in mice administered GalN and LPS in combination. A nitrosyl-heme signal in
      10,000 g supernatant of liver homogenate, due to cytochrome P450 (P450) combining
      with NO, NO-P450, was detected at more than ten hr and even more after
      administration of LPS by electron spin resonance (ESR) measurements at 77 degrees
      K. The strongest NO-P450 signal and most extreme elevation of aspartate
      oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT),
      and lactate dehydrogenase (LDH) in serum and of lysosomal enzyme activity in
      plasma were observed in the GalN + LPS group. Their potency was greater than in
      the 10 mg/kg LPS group, which was even greater than in the LPS 1 mg/kg group. The
      aniline hydroxylase activity was inversely proportional to NO-P450 signal
      intensity. It appears that NO might contribute to LPS-induced hepatic damage in
      GalN-sensitized mice through degeneration and inactivation of liver microsomal
      enzymes by binding P450 active sites.

PMID- 10073340
TI  - Epizootic podoknemidokoptiasis in American robins.
AB  - Epizootics of scaly leg disease caused by infection with the submacroscopic mite
      Knemidokoptes jamaicensis (Acari: Knemidokoptidae) in migratory American robins
      (Turdus migratorius) from a residential area of Tulsa (Oklahoma, USA) are
      documented during the winters (December through February) of 1993-94 and 1994-95.
      Estimates of 60 to > 80% of the birds in several different flights arriving in
      the area had lesions consistent with knemidokoptic mange. Epizootic occurrence of
      K. jamaicensis also is confirmed incidentally in American robins from Georgia
      (USA) in 1995 and 1998 and in Florida (USA) in 1991. These are the first
      confirmed epizootics of scaly leg attributed to infections with mites
      specifically identified as K. jamaicensis in North America. Severity of observed
      lesions in American robins ranged from scaly hyperkeratosis of the feet and legs
      to extensive proliferative lesions with loss of digits or the entire foot in some
      birds. Histologically, there was severe diffuse hyperkeratosis of the epidermis
      which contained numerous mites and multifocal aggregates of degranulating to
      degenerating eosinophilic heterophils; there was mild to severe superficial
      dermatitis with aggregates of eosinophilic heterophils and some mononuclear
      cells. Based on limited data from affected captive birds in Florida, we
      questioned the efficacy of ivermectin as an effective acaricide for
      knemidokoptiasis and propose that conditions associated with captivity may
      exacerbate transmission of this mite among caged birds. While knemidokoptic mange
      apparently can result in substantial host morbidity and possibly mortality, the
      ultimate impact of these epizootics on American robin populations presently is
      unknown.

PMID- 10073341
TI  - Pathology of Newcastle disease in double-crested cormorants from Saskatchewan,
      with comparison of diagnostic methods.
AB  - Newcastle disease (ND) in juvenile double-crested cormorants (Phalacrocorax
      auritus) occurred several times since 1975, but there are relatively few studies
      on its pathology and diagnosis. In order to describe the distribution of
      Newcastle disease virus (NDV) and associated lesions in cormorants with ND and to
      compare diagnostic methods, 25 cormorants with nervous signs from a ND epizootic
      in Saskatchewan in 1995 (NDE cormorants) were compared with 18 negative control
      cormorants. Tissues of these birds were examined by necropsy, histology, virus
      isolation, immunohistochemistry, serology, and reverse transcriptase-polymerase
      chain reaction (RT-PCR) methods. The NDE cormorants had a characteristic non
      suppurative encephalomyelitis, with a significantly higher prevalence of neuronal
      necrosis, gliosis, perivascular infiltration with mononuclear cells, and
      endothelial hypertrophy than control cormorants. These lesions were found more
      frequently in the cerebellum and brain stem than in other parts of the central
      nervous system. Immunohistochemically, NDV antigen was limited to neurons, glial
      and endothelial cells in the central nervous system, and to tubular epithelial
      cells in the kidney. Newcastle disease virus was isolated with the highest
      prevalence (4/5) and the highest concentration (10(4.8) ELD50/g) from the kidney.
      The virus isolates often did not agglutinate erythrocytes in the standard
      hemagglutination test; the presence of NDV was confirmed by use of an indirect
      immunoperoxidase assay. By RT-PCR, NDV was detected in kidney and jejunum of a
      NDE cormorant. There was no significant difference between sensitivity of
      histology, virus isolation, and serology for detecting ND in NDE cormorants.

PMID- 10073342
TI  - Experimental Narthecium ossifragum nephrotoxicity in cervids from Norway.
AB  - One moose (Alces alces), two red deer (Cervus elaphus), two reindeer (Rangifer
      tarandus) and two fallow deer (Dama dama) were dosed intraruminally with an
      aqueous extract made from 30 g of bog asphodel (Narthecium ossifragum) (wet
      weight) per kg live weight. The moose and one of the two reindeer were mildly
      depressed and had reduced appetite 3 to 7 days and 1 to 4 days after dosing,
      respectively. The serum creatinine and urea concentrations increased markedly in
      the moose and red deer, and moderately in the reindeer. No increase in serum
      creatinine and urea was observed in the fallow deer. Histopathological
      examination of the kidneys of the animals, killed 8 to 10 days after dosing,
      revealed tubular epithelial cell degeneration, necrosis, and regeneration in the
      moose, red deer and reindeer. The renal lesions were severe in the moose,
      moderate in the red deer and mild in the reindeer. No histopathological lesions
      were seen in the kidneys of the fallow deer.

PMID- 10073343
TI  - Age-related plasma chemistry changes in houbara and kori bustards in the United
      Arab Emirates.
AB  - Plasma chemistry parameters were measured in adult (> 1.5 yr) and juvenile (4-8
      and 9-16 wk) captive houbara bustards (Chlamydotis undulata macqueenii) and from
      adult (> 1.5 yr) and juvenile (4-8, 9-16, 17-24, 25-32, 33-40 and 41-52 wk)
      captive kori bustards (Ardeotis kori) to study age-related changes. A comparison
      of the values obtained was made between adult and juvenile bustards of both
      species and from the literature with other bustard species. Significant
      differences between adult and juvenile bustards of both species were found for
      glucose, total protein, alkaline phosphatase (ALKP), aspartate amino transferase
      (AST), lactate dehydrogenase, and calcium. Some parameters, such as calcium,
      showed comparable age-related changes in both species. In contrast, other
      parameters showed clear differences in the type (ALT, AST) or magnitude (ALKP) of
      age-related change between the species, demonstrating the importance of
      determining normal values for individual species. The results obtained from this
      study provide blood chemistry values for these species and demonstrate age
      related differences between adult and juvenile birds.

PMID- 10073344
TI  - Relative efficiency of succinylcholine, xylazine, and carfentanil/xylazine
      mixtures to immobilize free-ranging moose.
AB  - We compared the efficiency of succinylcholine chloride, xylazine hydrochloride
      and carfentanil/xylazine mixtures in immobilizing 364 free-ranging moose (Alces
      alces) between 1987 and 1997 in Quebec (Canada). With succinylcholine chloride
      (0.070, 0.062, 0.051 mg/kg of estimated body weight for calves, juveniles and
      adults), 63% of the 252 immobilization attempts led to complete immobilization
      and marking, whereas 7% of the darted animals died of respiratory paralysis
      during handling. The moose took an average of 13 min to lay down after darting
      (down time). Injection of xylazine (3.67-4.22 mg/kg) permitted sedation (the
      animal laid down but got up again when approached) or complete immobilization in
      78% of the 40 darted adult moose, the mean down time being 8.7 min. No mortality
      was noted with this drug but 58% of the marked animals were only sedated. The use
      of RX821002A (0.058 mg/kg) as an antagonist, permitted a mean recovery time of
      2.8 min after intravenous injection. With the carfentanil/xylazine mixtures
      (0.0071 and 0.181 mg/kg), 96% of the immobilization trials (n = 72) led to
      complete (88%) or partial (8%) immobilization, but 6% of the moose died several
      days after capture. The mean down time was 6.6 min, and injection of naltrexone
      (0.709 mg/kg) antagonized the effect of the immobilizing agent within 3.7 min.
      The respiratory rate was higher (P < 0.05) among moose immobilized with xylazine
      (35/min) than among those immobilized with carfentanil/xylazine mixtures (19/min)
      but this variation could be related to a longer pursuit time (z = 3.60; P < 0.01)
      and higher stress levels during handling. Rectal temperature also was higher with
      xylazine but the difference was small (39.7 vs. 39.3, P = 0.03) and did not
      differ significantly between the sexes (P > 0.05). Considering loss of materials
      and helicopter flight time due to non-successful marking trials,
      carfentanil/xylazine mixtures were the least expensive ($333 Cdn/animal).

PMID- 10073345
TI  - Causes of mortality of the Wyoming toad.
AB  - Wyoming toads (Bufo baxteri) that died from January 1989 to June 1996 were
      submitted to the Wyoming State Veterinary Laboratory (Laramie, Wyoming, USA) for
      postmortem evaluation. These consisted of 108 free-ranging toads and 170 animals
      from six captive populations. Ninety-seven (90%) of 108 free-ranging toad
      carcasses were submitted during September and October. From 1989 to 1992, 27
      (77%) of 35 mortalities in the captive populations occurred in October, November,
      and December. From 1993 to 1996, mortality in captive toads occurred without a
      seasonal pattern and coincided with changes in hibernation protocols that no
      longer mimicked natural cycles. Cause of mortality was determined in 147 (53%) of
      the 278 cases. Mycotic dermatitis with secondary bacterial septicemia was the
      most frequent diagnosis in 104 (71%) of 147 toads. Basidiobolus ranarum was found
      by microscopic examination of skin sections in 100 (96%) of 104 of these
      mortalities. This fungus was isolated from 30 (56%) of 54 free-ranging and 24
      (48%) of 50 captive toads. This research documents the causes of mortality for
      both free-ranging and captive endangered Wyoming toads over a 7 yr period.

PMID- 10073346
TI  - Experimental exposure of Canadian toads to Basidiobolus ranarum.
AB  - Experimental transmission of the fungus Basidiobolus ranarum was induced in two
      treatment groups of Canadian toads (Bufo hemiophrys) and caused a fatal mycotic
      dermatitis. Seven of 10 (70%) toads that had their ventral skin mildly abraded
      and exposed to B. ranarum developed hyperemia, and sloughing of their ventral
      skin and died. Toads with abraded ventral skin or exposure to infected skin also
      were affected statistically at a higher rate than those with abraded skin and
      exposure to pure cultures of B. ranarum inoculated into their water source. Of
      toads showing clinical disease, B. ranarum was identified by both impression
      smears and histology in all cases, but not from toads that appeared clinically
      healthy. The organism was cultured from 5 of 7 (71%) toads with clinical disease
      but not from any toad that appeared clinically healthy (n = 28). This study
      documents methods of experimental transmission of B. ranarum, an organism
      responsible for causing a mycotic dermatitis that is fatal to toads.

PMID- 10073347
TI  - Mortality of captive Canadian toads from Basidiobolus ranarum mycotic dermatitis.
AB  - Twenty-six adult free-ranging Canadian toads (Bufo hemiophrys) were collected
      from northeastern North Dakota (USA) during the last week of August 1994 and
      placed in captivity. During late December and January 1995, 21 Canadian toads
      died. Clinical signs included increased time sitting in water bowls, darkened
      dorsal skin, constant arching of their backs, and hyperemia and sloughing of
      ventral epidermis. The condition progressively worsened until death occurred
      within 5 to 7 days after onset of clinical disease. Mycotic dermatitis due to
      Basidiobolus ranarum was diagnosed in all toads and the fungus was isolated from
      11 (52%) of 21 toads. Histology of the ventral skin and digits revealed numerous
      fungal spherules and occasional hyphae without significant inflammatory reaction.
      This condition clinically resembled red leg associated with Aeromonas hydrophila
      and many other bacterial organisms, and the diseases could be confused without
      appropriate diagnostic tests. This also is the first report of B. ranarum causing
      clinical disease in a toad species.

PMID- 10073348
TI  - Mucormycotic dermatitis in captive adult Wyoming toads.
AB  - During late May 1995, 50 adult captive endangered Wyoming toads (Bufo baxteri)
      were brought out of hibernation. Approximately 3 to 10 days after hibernation
      emergence, all toads were hormonally induced to breed, and paired. Each pair was
      placed in their own breeding tank. Four toads developed clinical signs of disease
      which included lethargy and multiple (4 to 12) small (2 mm) raised hyperemic
      nodules with white fuzzy caps on the ventral skin. The condition progressively
      worsened until death occurred, within 3 to 6 days. Mycotic dermatitis caused by
      Mucor sp. was diagnosed in the four toads through histology and isolation of the
      organism. This is the first case report of a Mucor sp. causing a fatal dermatitis
      in an amphibian without significant inflammatory response and without systemic
      involvement.

PMID- 10073349
TI  - Peritoneal coccidioidomycosis in a mountain lion in California.
AB  - An adult mountain lion (Felis concolor) from the vicinity of Weldon, California
      (USA) was necropsied following euthanasia due to emaciation and proximity to semi
      rural housing. There were spherules consistent with Coccidioides immitis within
      peritoneal surfaces with granulomatous inflammation and fungi consistent with C.
      immitis were cultured from abdominal fluid. This is the first reported case of
      coccidioidomycosis in a wild mountain lion.

PMID- 10073350
TI  - Oestrid myiasis in European mouflon from Spain.
AB  - From February 1992 to March 1997, 245 European mouflon (Ovis orientalis musimon)
      from Sierras de Cazorla, Segura y Las Villas Natural Park (southern Spain) were
      surveyed for oestrid larvae in order to estimate prevalence and mean intensity of
      parasitism by Oestrus ovis. Over 46 percent of the animals surveyed were
      infected, with a mean intensity of 9.6 larvae/host parasitized. No significant
      differences in prevalence rates between host sexes were observed, but older
      mouflons were infected with more larvae than younger ones.

PMID- 10073351
TI  - A possible new piroplasm in lions from the Republic of South Africa.
AB  - A small piroplasm was detected in blood smears from lions (Panthera leo) in the
      Kruger National Park (KNP; Republic of South Africa) during 1991/1992. The
      parasite was identified provisionally as Babesia felis, but sera from these lions
      tested negative to B. felis antigen in the indirect immunofluorescent antibody
      test (IFAT). Blood from an infected lion was subsequently subinoculated into a
      domestic cat and two leopards in an attempt to identify the parasite. A lion also
      was infected with B. felis (from a cat). Serum samples collected from these
      animals were tested against B. felis, the KNP small piroplasm, and Cytauxzoon
      felis antigen in the IFAT. The serological results indicate that the KNP small
      piroplasm isolated from the lion is probably a distinct species from B. felis and
      C. felis.

PMID- 10073352
TI  - Naturally occurring hepatozoonosis in coyotes from Oklahoma.
AB  - Nine of 16 free-ranging coyotes (Canis latrans) from central Oklahoma (USA) had
      naturally acquired infections of Hepatozoon americanum. Infections were confirmed
      by recognition of tissue stages closely resembling H. americanum in skeletal and
      cardiac muscle. At the time coyotes were collected they were infested with a
      variety of ticks, including adult Gulf Coast ticks (Amblyomma maculatum). We
      propose that the high prevalence of H. americanum in this small sample of free
      ranging coyotes and the ability of these same animals to harbor adult populations
      of A. maculatum is an important component of the epizootiology of canine
      hepatozoonosis in North America.

PMID- 10073353
TI  - Acanthocolpid metacercariae in the sea bass from Alejandro Selkirk Island, Chile.
AB  - Morphological characteristics of a metacercaria from muscle of 15 sea bass
      Caprodon longimanus (Serranidae) collected near Alejandro Selkirk Island (Chile)
      in the south-eastern Pacific Ocean indicate that it belongs to the genus Manteria
      (Acanthocolpidae). All metacercarie were encapsulated with connective tissue. The
      prevalence of infection was 100%, with 64% of metacercariae were located between
      dorsal pterygiophores and dorsal fin base. Mean intensities of metacercariae did
      not differ significantly with respect to sex of the fish. There was no
      significant correlation with intensities of infection and condition in the host.

PMID- 10073354
TI  - Trichinella sp. in wolves from interior Alaska.
AB  - Tongue samples were collected from 148 wolf (Canis lupus) carcasses during 1993
      and 1994 near Fairbanks (Alaska, USA). A standard peptic digestion procedure was
      used to detect Trichinella sp. larvae. Larvae were found in 54 of 148 (36%)
      samples. There was no significant difference in sex-specific prevalence.
      Prevalence was significantly related to age. There was no relationship between
      the number of larvae/g of host tissue and the age or sex of the host. Trichinella
      spp. infection may cause illness in individual wolves. However, there was no
      indication the parasite had any impact on the population.

PMID- 10073355
TI  - Disseminated granulomas associated with nematode larvae in a shortfin mako shark.
AB  - A shortfin mako shark (Isurus oxyrinchus) caught in 1996 by sportfishermen in
      Long Island (New York, USA) had many granulomas containing larval nematodes.
      Granulomas were present in the myocardium, spleen, pancreas, stomach, spiral
      intestine, hematopoietic tissue within the anterior kidney, and in the branchial
      septum and primary lamellae of the gills. Epicardial hyperplasia and
      granulomatous myocarditis were associated with the larvae. Although
      identification of the larvae was impossible due to lack of distinct morphological
      features, they resembled dracunculoid larvae previously reported from sharks.

PMID- 10073356
TI  - Meningeal worm in free-ranging deer in Nebraska.
AB  - The meningeal worm (Parelaphostrongylus tenuis) was found in 22 (7%) of 300 white
      tailed deer (Odocoileus virginianus) (257 adults, 43 fawns) examined from
      Nebraska (USA) during November 1996. None of 53 mule deer (Odocoileus hemionus)
      (47 adults and 6 fawns) examined were infected. Twenty-two white-tailed deer from
      18 counties in eastern Nebraska were infected with Parelaphostrongylus tenuis.
      This is the first record of P. tenuis in white-tailed deer from this state.

PMID- 10073357
TI  - Absence of tuberculosis in free-ranging deer in Nebraska.
AB  - Lymph nodes from 271 white-tailed deer (Odocoileus virginianus) and mule deer
      (Odocoileus hemionus) in Nebraska (USA) were examined microscopically for
      tuberculoid lesions. Lymph nodes lesions in at least one node were found in 12
      deer. Lesions were examined with Zeihl-Neelson acid fast stains and by polymerase
      chain reactions using M. bovis specific probes. No evidence of tuberculosis was
      found. The small granulomatous lesions were likely caused by other bacteria.

PMID- 10073358
TI  - Antibodies against Leptospira interrogans in California sea lion pups from Gulf
      of California.
AB  - One hundred and twenty-five serum samples from California sea lion (Zalophus
      californianus californianus) pups, and one from an adult female from eight
      reproductive rookeries located in seven islands in the Gulf of California
      (Mexico), were collected during the 1994-96 reproductive seasons. These were
      tested for antibodies to 19 serovars of Leptospira interrogans using a
      Microscopic Agglutination Test (MAT). Forty-one samples (32%) had antibody levels
      from 1:20 to 1:320 to one or more serovars. The most frequently detected
      serotypes were Leptospira interrogans hardjo (n = 13), cynopteri (8), ballum (6),
      and szwajizak (5). Serovars with the highest prevalence were Leptospira
      interrogans hardjo and serjoe (1:320), ballum (1:160), and cynopteri,
      girppotyphosa, and tarassovi (1:80). Based on these results, exposure of sea
      lions to L. interrogans serovar hardjo seems to be relatively common among
      colonies located in the islands of the Gulf of California in contrast with those
      located on the Pacific coast, where the most frequently detected serovar is L.
      interrogans serovar pomona.

PMID- 10073359
TI  - Serosurvey for antibodies against Brucella abortus and Leptospira interrogans in
      pampas deer from Brazil.
AB  - A survey for antibodies against Brucella abortus, and Leptospira interrogans was
      conducted on 17 pampas deer (Ozotocerus bezoarticus) from Pantanal Matogrossense
      (State of Mato Grosso do Sul, Brazil) and on 24 pampas deer from Parque Nacional
      de Emas (State of Goias, Brazil). Antibodies against B. abortus were detected by
      plate agglutination, rose Bengal, and complement fixation tests; antibodies
      against Leptospira interrogans were detected by the microscopic agglutination
      test. All sera were negative for B. abortus antibodies and all deer sera from
      Parque Nacional de Emas were negative for L. interrogans antibodies. Four (24%)
      of 17 sera from Pantanal Matogrossense were positive for L. interrogans serovar
      (n = 2) hardjo, wolffi (n = 1) and mini (n = 1). While these diseases do not
      appear to be of major importance to the health status of Pampas deer, it appears
      that deer are reservoir for leptospirosis in one of the study areas.

PMID- 10073360
TI  - Absence of Escherichia coli O157 in a survey of wildlife from Trinidad and
      Tobago.
AB  - Fecal, cloacal, or rectal swabs of free-ranging and captive mammalian and avian
      wildlife in Trinidad and Tobago were cultured for non-sorbitol fermenting
      Escherichia coli and tested for O157:H7 strains. Ability of E. coli strains to
      produce hemolysin and mucoid colonies also was investigated. Of 271 free-ranging
      mammals tested, 158 (58%) yielded E. coli; only one (< 1%) bacterial isolate was
      a non-sorbitol fermenter which was not agglutinated by O157 antiserum. All
      isolates were negative for hemolysin production and mucoid colonial growth. Two
      hundred and sixty-three (90%) of 293 free-flying birds were positive for E. coli
      and all isolates were sorbitol fermenters and negative for production of
      hemolysin and mucoid growth. Of 175 captive wild animals from individual backyard
      farms and a government demonstration farm, 145 (83%) yielded E. coli with four
      (2%) non-sorbitol fermenters; all were negative for O157 strains, hemolysin
      production, and mucoid colonial growth. Of 373 animals in a zoo, 250 (67%) were
      positive for E. coli with only two (0.5%) non-sorbitol fermenters. All strains
      were non-hemolytic and non-mucoid farms. It appears that free-ranging and captive
      avian and mammalian wildlife are not important reservoirs of O157:H7 strains of
      E. coli in Trinidad and Tobago.

PMID- 10073361
TI  - Feline viruses in wildcats from Scotland.
AB  - Few data are available on the prevalence of feline viruses in European wildcats
      (Felis silvestris). Previous surveys have indicated that wildcats may be infected
      with the common viruses of domestic cats, apart from feline immunodeficiency
      virus (FIV). In the present study, 50 wildcats trapped throughout Scotland (UK)
      between August 1992 and January 1997 were tested for evidence of viral infection.
      All were negative for FIV by several serological or virological methods. By
      contrast, 10% of the cats were positive for feline leukemia virus (FeLV) antigen
      and infectious virus was isolated from 13% of a smaller subset. Of the wildcats
      tested for respiratory viruses, 25% yielded feline calicivirus (FCV) and although
      no feline herpesvirus was isolated, 16% of the samples had neutralizing
      antibodies to this virus. Antibodies to feline coronavirus (FCoV) were found in
      6% of samples. Feline foamy virus (FFV) was an incidental finding in 33% of
      samples tested. This study confirms that wildcats in Scotland are commonly
      infected with the major viruses of the domestic cat, except for FIV.

PMID- 10073362
TI  - Ectromelia in Morelet's crocodile from Belize.
AB  - Two Morelet's crocodiles (Crocodylus moreletii) captured on 21 March 1997 and 20
      April 1998 in the New River system, Belize exhibited ectromelia of one forelimb.
      External and radiograph examination appears to indicate limb agenesis of unknown
      etiology, as there is no apparent scarring or skeletal trauma. These two
      individuals represent the only cases of missing limbs from 642 individuals
      captured in this study and to our knowledge, the first reported cases in
      Morelet's crocodile. Several factors including age and diet of the reproducing
      female, extremes in nest conditions (egg incubation temperature and humidity),
      and exposure to environmental contaminants can cause developmental abnormalities
      in crocodilians and may have contributed to the condition observed in these
      animals. Survival rates for hatchling crocodilians are generally low, and
      embryonic malformations such as ectromelia may constitute an added disadvantage
      to survival. However, both individuals examined in this study were vigorous and
      appeared in good condition.

PMID- 10073363
TI  - Toxic nephrosis in moose in Norway.
AB  - During the summers 1995/96, toxic nephrosis was diagnosed in nine free-living
      moose (Alces alces) from Aust-Agder County in southern Norway. Histopathological
      kidney lesions included tubular degeneration and necrosis, tubular regeneration,
      and interstitial fibrosis. The disease was probably caused by ingestion of the
      toxic plants, bog asphodel (Narthecium ossifragum) or oak (Quercus spp.).

PMID- 10073364
TI  - Tear production in three captive wild herbivores in Israel.
AB  - The Schirmer tear test (STT) I was performed to evaluate tear production in 12
      captive Nubian ibex (Capra ibex nubiana), 10 captive Burchell's zebras (Equus
      burchelli) and five Arabian oryx (Oryx leucoryx) at the Tel-Aviv Ramat-Gan
      Zoological Center (Israel). Mean (+/- standard deviation) STT values were 13.2 +/
      5.1 mm/min in the ibex, 23.4 +/- 3.4 mm/min in the zebra and 12.7 +/- 4.8 mm/min
      in the oryx. There were no significant effects of gender, age, weight, or side of
      the eye. There were no significant differences in STT values between ibex and
      oryx, but tear production in both species was significantly lower than in zebras.
      Knowledge of normal tear production values is important for the differential
      diagnosis of conjunctivitis and keratitis in these species.

PMID- 10073365
TI  - Synovial chondromatosis in raptors.
AB  - Fourteen raptors, consisting of 13 great horned owls (Bubo virginianus) and one
      red-tailed hawk (Buteo jamaicensis), from central and north central Minnesota,
      western Wisconsin, and eastern South Dakota (USA) were admitted to a raptor
      rehabilitation center between June 1992 and June 1995, with perisynovial and
      synovial chondromatosis affecting multiple joints. Birds were severely
      debilitated primarily due to loss of shoulder motion. The etiology of these
      lesions in raptors is unknown.

PMID- 10073366
TI  - Uterine adenocarcinoma in a captive sika deer.
AB  - A uterine adenocarcinoma with widespread visceral implantation and lymphatic
      metastases is described in a 4-yr-old captive nulliparous sika deer (Cervus
      nippon). The tumor was histologically characterized by proliferation of
      irregularly shaped acini and tubules lined by single- or multi-layered
      pleomorphic epithelial cells, which were sometimes multinucleated and contained
      PAS positive mucin. The neoplastic tissue was invasive and showed a marked
      desmoplastic reaction. A relationship between the tumor and a hormonal imbalance
      could not be ruled out. This is the first report of a tumor of the reproductive
      tract in a cervid.

PMID- 10073367
TI  - Field immobilization and euthanasia of American opossum.
AB  - Seventeen recently trapped opossum, Didelphis virginiana, (median weight 2.45 kg;
      range = 1.6-5.0 kg; quartiles = 1.8-3.3 kg) were immobilized with either telazol
      (15 or 30 mg/kg) or a mixture of medetomidine (100 micrograms/kg), butorphanol
      (0.2 mg/kg), and ketamine HCl (10 mg/kg) based on estimated weights. Anesthetized
      animals were subjected to cardiac puncture for blood withdrawal and toe pinch.
      Euthanasia was accomplished by intracardiac administration of 1 ml of
      concentrated pentobarbital sodium/phenytoin solution. Weights were underestimated
      for 14 of 17 animals, but were within 0.5 kg of the actual weight. Both drug
      combinations provided rapid and calm immobilization. Median time to recumbency
      for the medetomidine-butorphanol-ketamine group (n = 5) was 6 min (range = 4-10
      min; quartiles = 6 and 8 min). The median time to recumbency was not
      statistically different for the low (n = 6) and high dose (n = 6) telazol groups,
      3 and 3.5 min respectively (quartiles 3; 3.5 and 4; 5.5 min). The stronger heart
      beat with telazol immobilization facilitated cardiac puncture. All five animals
      administered the medetomidine-butorphanol-ketamine mixture and three of six
      animals given the low telazol dose reacted to cardiac puncture. Only one of six
      animals given the estimated 30 mg/kg dose of telazol reacted slightly to cardiac
      puncture. We conclude that 30 mg/kg telazol provides sufficient immobilization
      and analgesia to allow accurate cardiac puncture of the opossum if the procedure
      is performed within 5 to 10 min of recumbency. Intracardiac administration of
      concentrated pentobarbital sodium/phenytoin solution followed by bilateral
      thoracotomy provides appropriate euthanasia suitable for field situations.

PMID- 10073368
TI  - An additional case of leptospirosis in a harbor seal.

PMID- 10073370
TI  - Outcome in schizophrenia: beyond symptom reduction.
AB  - Although some patients with schizophrenia may have a single episode and recover,
      the vast majority remain ill and unable to work for life. In the United States,
      patients with schizophrenia use 2.5% of the annual total health care allocations.
      The atypical antipsychotics, particularly when combined with psychosocial
      treatment, hold the promise of improving outcome and reducing the economic burden
      on society. Both clinical outcome and cost effectiveness are best evaluated in
      the context of a comprehensive assessment of a range of meaningful outcome
      measures studied in clinical situations. Evidence exists that the atypical
      antipsychotics not only reduce positive and negative symptoms and cause fewer
      side effects than conventional neuroleptics, but also lessen cognitive
      impairment, lead to a better quality of life, and have antidepressant effects,
      all of which should result in improved outcome in patients with schizophrenia.
      Increasing the availability of the atypical agents should be cost effective for
      society by restoring productivity in some patients with schizophrenia.

PMID- 10073371
TI  - Methods of cost-effectiveness analysis in the evaluation of new antipsychotics:
      implications for schizophrenia treatment.
AB  - Because health care payers are increasingly interested in learning whether new
      treatments offer value for money, there has been an abundance of research into
      the cost-effectiveness of pharmacologic therapies in the United States. In the
      past few years, a number of studies comparing the cost-effectiveness of the
      conventional neuroleptics with that of the atypical antipsychotics have been
      published. Cost-effectiveness analyses show the relationship between the
      resources used (costs) and the health benefits achieved (effects) for a health or
      medical intervention compared with an alternative strategy. Ideally, the analyses
      can help decision makers improve the health of the population by better
      allocating society's limited health care resources. However, the extent to which
      cost-effectiveness data are actually used in decision making is unclear. The
      analyses are sometimes viewed with skepticism, in part because studies differ in
      their methodological approaches. Recently, the U.S. Panel on Cost-Effectiveness
      in Health and Medicine offered recommendations for standard methodological
      practices, which may help improve the quality of studies and the acceptability of
      the approach in the future. The issue is particularly important in light of new
      legislation governing how the Food and Drug Administration will regulate
      promotional claims made by drug companies regarding health economic information.

PMID- 10073372
TI  - Mental health care from the public perspective: the Texas Medication Algorithm
      Project.
AB  - Medication treatment algorithms have been suggested as a strategy to provide
      uniform care at predictable costs. The Texas Medication Algorithm Project is a 3
      phase study designed to provide solid data on the usefulness of medication
      algorithms. In phase 1, medication algorithms for the treatment of schizophrenia,
      major depressive disorder, and bipolar disorder were developed. Phase 2 was a
      feasibility study of these algorithms, and phase 3, now underway, compares the
      costs and outcome in 3 groups, one using a combination of an algorithm and
      patient/family education, a second using treatment as usual in a clinic that uses
      an algorithm for a different disorder, and a third using treatment as usual in a
      nonalgorithm clinic.

PMID- 10073373
TI  - Cost-utility analysis in schizophrenia.
AB  - Estimation of quality of life is important to the study of the pharmacoeconomics
      of schizophrenia. The subject has gained popularity among policymakers,
      clinicians, and patients and their families, since the advent of new
      antipsychotic medications that are more expensive than older drugs yet have been
      shown to cause fewer side effects. Quantifying quality of life has been
      difficult, since studies often inconsistently define the concept or use rating
      scales that are inappropriate for the patient population. Utility analysis is a
      procedure that calculates subjects' preferences regarding living with various
      health states, given such options as trading more years of life at a lowered
      health state for dying sooner but having a strong health state during the last
      years of life. The feasibility of performing utility analysis among patients with
      schizophrenia was recently examined in a study carried out by the authors. This
      article reflects initial observations from that study of utility analysis and
      includes a discussion of problems still facing the study of quality of life and
      utility analysis.

PMID- 10073374
TI  - The Wisconsin Quality of Life Index: a multidimensional model for measuring
      quality of life.
AB  - The Wisconsin Quality of Life Index (W-QLI) is a multidimensional model for
      measuring quality of life. This model assumes that quality of life is comprised
      of 9 dimensions: life satisfaction, occupational activities, psychological well
      being, physical health, social relations, economics, activities of daily living,
      symptoms, and the patient's own goals. The W-QLI takes into account the different
      perspectives of the patient, the patient's family, and the clinician, both
      currently and over time. An accompanying taxonomy and patient outcome report can
      be used in clinical practice to group the patient's goals and to track the
      attainment of the goals over time, as well as to show the agreements and
      disagreements between the patient and clinician in terms of how satisfied each is
      with the patient's progress. The W-QLI, taxonomy, and outcome report can also
      incorporate the service provider's goals and can be used to examine program
      results.

PMID- 10073375
TI  - Perspective and the measurement of costs and benefits for cost-effectiveness
      analysis in schizophrenia.
AB  - A valid and compelling cost-effectiveness analysis of psychopharmacologic
      treatment of schizophrenia requires the application of analytically rigorous
      methods. All cost-effectiveness analyses must consider the issue of perspective
      as the well as the appropriate measurement of benefits and costs. Many of these
      issues are particularly difficult to address in the case of schizophrenia. Since
      costs may be borne by a wide range of parties, the choice of perspective is of
      critical importance. The fact that treatments for schizophrenia can extend life
      and the complexities raised by taking a broad perspective on the benefits and
      costs of treating schizophrenia can create challenges in the measurement of both
      benefits and costs. The measurement of benefits through quality-adjusted life
      years is also crucial in demonstrating the cost-effectiveness of treatments for
      schizophrenia, but is challenging because of the difficulty of measuring quality
      of life in schizophrenic patients. Attention to these important methodological
      issues is essential if cost-effectiveness analyses are to be useful in
      shepherding scarce resources to worthwhile treatments for patients with
      schizophrenia.

PMID- 10073376
TI  - What about the patient?
AB  - Our mental health care system fails to serve the very people whose suffering that
      system ostensibly exists to alleviate. This article relates the stories of 3
      people who fell through the cracks of this system. An alternative approach, the
      Integrated Services Agency (ISA), has been implemented in California and offers
      hope to persons with schizophrenia. The ISA approach focuses on the expressed
      needs of the members it exists to serve, and both members and staff have
      experienced changes in their roles and expectations. Staff and members have
      learned that engagement with the "outside world" involves taking risks but that
      risk avoidance only perpetuates the status quo. The ISA approach rewards growth
      and patients' being well rather than rewarding docility and illness. Medication
      is neither ordered nor assigned, but chosen in a collaboration between staff and
      members. ISAs have returned care to the mental health care system.

PMID- 10073377
TI  - The Risperidone Outcomes Study of Effectiveness (ROSE): a model for evaluating
      treatment strategies in typical psychiatric practice.
AB  - We describe the design of a multicenter, randomized clinical trial to compare
      clinical, quality-of-life, and economic outcomes in patients with schizophrenia
      or schizoaffective disorder who were treated with risperidone or any of 13
      conventional antipsychotic drugs approved for use in the United States. This 1
      year trial was designed to approximate conditions of typical clinical practice:
      protocol-mandated care was minimized, and all health services (including
      medication) were provided according to usual community practices. Measures of
      interest included changes in psychiatric symptoms, medication side effects,
      health-related quality of life, satisfaction with drug therapy, therapy
      switching, rehospitalization for the management of relapse, the use of
      psychiatric services of all types, and the cost of psychiatric care. We review
      the rationale for this type of trial and discuss the potential value of such
      trials in setting policy and in clinical practice.

PMID- 10073378
TI  - Cost of treating mental illness from a managed care perspective.
AB  - The issue of cost-effectiveness in the pharmacoeconomics of mental illness is a
      new concept. As methodologies for exploring this subject unfold, the most
      fundamental objective for health care professionals and managed care officials is
      to find ways in which currently available resources can be used most effectively.
      The managed care perspective is highly cost-based within the market it serves. In
      addition to cost, other factors that influence the managed care perspective are a
      short-term focus, segmentation of budgets, and measurable indicators of outcome,
      cost, and quality of care. The cost of new psychopharmacology--especially
      antidepressants and antipsychotics--may be many times that of traditional drugs,
      and concern about increased drug costs is present in many managed care
      organizations. Several issues must be addressed to prevent restriction of
      pharmacotherapeutics in managed care settings. For example, a focus on both
      outcomes and practice guidelines is needed to help allocate limited resources
      fairly. This article suggests ways in which available resources can be used more
      effectively to treat mental illness within the present health care system.

PMID- 10073379
TI  - Panel on cost-effectiveness in health and medicine recommendations: identifying
      costs.
AB  - The assignment of costs in a cost-effectiveness analysis is a complex and
      disputed issue. The Panel on Cost-Effectiveness in Health and Medicine was
      convened to discuss standards that could be applied across a range of areas of
      cost-effectiveness. Additionally, the Panel had a mandate to resolve some
      controversial issues about the practice of cost-effectiveness that created
      difficulty in making comparisons across studies. The Panel proposed these
      guidelines: (1) Do at least some of the analysis from a social perspective; (2)
      Assign values to resources that reflect their opportunity costs; (3) Avoid zero
      counting of resources; (4) Avoid double counting of resources; (5) Make analyses
      only as exacting as necessary in a study. Difficulties in data collection were
      discussed. Among other questions considered by the panel were how to assign a
      value to the patient's time and which productivity costs to include in a cost
      effectiveness analysis. With tools and suggestions from the Panel on Cost
      Effectiveness in Health and Medicine, the cost analyst can report costs
      accurately and provide accurate comparisons of cost performance across states,
      trial modalities, or diseases.

PMID- 10073380
TI  - Pharmacoeconomic factors related to the treatment of schizophrenia. Concluding
      discussion.

PMID- 10073381
TI  - Effects of medical interventions on suicidal behavior. Introduction.
AB  - BACKGROUND: Knowledge of effective means of preventing suicide, based on research
      evidence, is strikingly limited, but there are indications that specific
      treatments may reduce suicidal risk in patients with major affective disorders.
      METHOD: An international symposium was held in Miami, Fla., February 26-28, 1998,
      to discuss current knowledge of the Effects of Medical Interventions on Suicidal
      Behavior. Participant experts prepared summary reports of their contributions.
      RESULTS: Participants considered what is known about the effects of medical
      treatments on suicidal risk, as well as proposed approaches to future research.
      This supplement summarizes the proceedings of the symposium. CONCLUSION: The
      symposium strongly supported the proposition that suicide is amenable to ethical
      scientific investigation, suggested that evidence supporting suicide risk
      reduction can be developed, and strongly encouraged studies to test the effects
      of specific interventions on suicidal risk. It also encouraged greater efforts at
      public and professional education to understand suicide as a result of mood and
      other psychiatric disorders, and to improve their early recognition and enhance
      timely access to effective treatment by the psychiatric and general medical
      community.

PMID- 10073382
TI  - The neurobiology of suicide risk: a review for the clinician.
AB  - Suicidal behavior has neurobiological determinants independent of the psychiatric
      illnesses with which it is associated. We have found that some patients with
      major depression are vulnerable to acting on suicidal impulses. This
      vulnerability results from the interaction between triggers or precipitants and
      the threshold for suicidal behavior. An important factor in setting an
      individual's threshold for acting on suicidal impulses is brain serotonergic
      function. Serotonin function has been shown to be lower in suicide attempters by
      studies measuring serotonin metabolites in cerebrospinal fluid and studies of
      prolactin response to fenfluramine. Postmortem studies of suicide victims also
      reveal decreased serotonin activity in the ventrolateral prefrontal cortex. New
      neuroimaging paradigms, such as positron emission tomography (PET), offer an
      opportunity to visualize serotonin function in vivo in a more direct way than has
      previously been available. This technology may provide the possibility of timely
      therapeutic intervention in patients at high risk for suicide.

PMID- 10073383
TI  - Genetics of suicide in depression.
AB  - Evidence is mounting that genetic factors may be included in the many
      determinants of suicide. Clinical studies of psychiatric patients have suggested
      that risk of suicidal behavior is increased by the presence of family history of
      suicidality, a claim that is also supported by findings of twin and adoption
      studies. In addition, molecular genetic studies have reported polymorphisms in
      the tryptophan hydroxylase gene that is involved in the synthesis of serotonin.
      The genetic susceptibility to suicide, however, tends to affect individuals only
      in association with stress or psychiatric illness.

PMID- 10073384
TI  - Expression of the myristoylated alanine-rich C kinase substrate (MARCKS) and
      MARCKS-related protein (MRP) in the prefrontal cortex and hippocampus of suicide
      victims.
AB  - BACKGROUND: Although suicide is a leading cause of death in the United States and
      represents a significant public health threat, little is known about the
      neurobiological or molecular factors that contribute to its pathophysiology. A
      number of studies now indicate that lithium has considerable efficacy in the
      prevention of suicide in patients with affective disorders, and accumulating
      evidence indicates that protein kinase C (PKC) and its substrates, in particular
      the myristoylated alanine-rich C kinase substrate (MARCKS), are primary targets
      of chronic lithium treatment. We therefore hypothesized that a dysregulation in
      MARCKS expression in key brain regions could contribute to the pathophysiology
      associated with suicide. To address this, we examined MARCKS, as well as the
      closely related MARCKS-related protein (MRP), mRNA expression in the hippocampus
      and dorsolateral prefrontal cortex of suicide victims and normal controls.
      METHOD: MARCKS and MRP mRNA expression was assessed by quantitative in situ
      hybridization histochemistry performed on postmortem hippocampal and dorsolateral
      prefrontal cortex sections from suicide (N = 9) and normal control (N = 10)
      brains. RESULTS: In the normal hippocampus, both MARCKS and MRP mRNA expression
      were highest in the granule cell layer and low-moderate in CA1, CA3, and hilus. A
      high level of MRP mRNA expression was also observed in the white matter of the
      fimbria/fornix. Neither MARCKS nor MRP mRNA expression levels differed
      significantly in the granule cell layer, CA3, hilus, or CA1 in suicide victims
      relative to normal controls (1-way ANOVA, p > .05). In the normal prefrontal
      cortex, MARCKS was expressed exclusively in gray matter (layers I-VI), whereas
      MRP was expressed in both gray and white matter. Neither MARCKS nor MRP mRNA
      expression levels in the gray and white matter regions of the dorsal prefrontal
      cortex differed between suicides and normal controls (1-way ANOVA, p > .05).
      CONCLUSION: The present findings are the first to demonstrate the expression and
      distribution of MARCKS and MRP in the human hippocampus and dorsolateral
      prefrontal cortex, and their expression pattern within these regions bears strong
      resemblance to those observed in the adult rat brain. Comparison of MARCKS and
      MRP mRNA expression in the hippocampus and prefrontal cortex of suicide victims
      and normal controls indicates that these 2 mRNAs are not differentially regulated
      in these regions. However, differences in MARCKS and MRP protein expression and
      function cannot be ruled out by the present findings.

PMID- 10073385
TI  - Modulation of CNS signal transduction pathways and gene expression by mood
      stabilizing agents: therapeutic implications.
AB  - In an attempt to find the key to reducing the excessive morbidity and mortality
      seen with mood disorders, our laboratory has been extensively investigating
      lithium's mechanisms of action in an integrated series of clinical and
      preclinical studies. We have found that the chronic administration of the 2
      structurally highly dissimilar agents, lithium and valproate, brings about a
      strikingly similar reduction in protein kinase C (PKC) alpha and epsilon isozymes
      in rat frontal cortex and hippocampus. In view of PKC's critical role in
      regulating neuronal excitability and neurotransmitter release, we have postulated
      that PKC inhibition may have antimanic efficacy. In a small study, we have found
      that tamoxifen (which, in addition to its estrogen receptor blockade, is also a
      PKC inhibitor) has marked antimanic efficacy. These exciting preliminary results
      suggest that PKC inhibitors may represent a novel class of improved therapeutic
      agents for bipolar disorder, and this is under further investigation. The
      beneficial effects of mood stabilizers require a lag period for onset of action
      and are generally not immediately reversed upon drug discontinuation; such
      patterns of effects suggest alterations at the genomic level. We have therefore
      undertaken a series of studies to investigate the effects of these agents on the
      AP-1 family of transcription factors and have found that both drugs increase AP-1
      DNA binding activity in areas of rodent brain ex vivo and in human neuronal cells
      in culture. Both treatments also increase the expression of a reporter gene
      driven by an AP-1-containing promoter, and mutations in the AP-1 sites of the
      reporter gene promoter markedly attenuate these effects. Both treatments also
      increase the expression of several endogenous proteins, whose genes are known to
      be regulated by AP-1. Although the precise mechanisms have not been fully
      elucidated, preliminary results suggest that these effects may be mediated, in
      part, by mitogen-activating protein kinases and glycogen synthase kinase 3beta.
      We have also utilized mRNA reverse transcription-polymerase chain reaction (RT
      PCR) differential display to identify concordant changes in gene expression
      induced by the chronic administration of both lithium and valproate. We have
      identified concordant changes in a number of cDNA bands by both lithium and
      valproate. Cloning and characterizing of these genes is currently underway. The
      identification of the functions of these genes offers the potential not only for
      improved therapeutics for reducing the morbidity and mortality associated with
      mood disorders, but may also provide important clues about the underlying
      pathophysiology.

PMID- 10073386
TI  - Depression screening as an intervention against suicide.
AB  - Depression is a common psychiatric disorder that can disrupt a person's health,
      work, and relationships, and--in some cases--lead to suicide. Disparity between
      the prevalence of depression and diagnosis and treatment of the disorder led to
      the creation in 1991 of National Depression Screening Day (NDSD), an annual
      nationwide screening program for depression. By raising awareness and reducing
      the stigma of depression, the national screening program addresses the problems
      of underdiagnosis and lack of treatment in persons suffering from the depressive
      disorder. Mental health professionals and colleagues in other specialties must
      reach out to depressed individuals and make it easier for them to access the
      health care system. This article discusses the origin and goals of NDSD, the NDSD
      model for the current community-based program, the results of NDSD screening, and
      the proposed future expansion of NDSD and the voluntary screening concept.

PMID- 10073387
TI  - Suicide, assisted suicide, and medical illness.
AB  - Medical illness is an important part of the motivation for suicide--a significant
      factor in about 50% of suicides in patients over the age of 50 years and 70% of
      suicides in patients over the age of 70 years. Depression, anxiety, and
      ambivalence about dying characterize both medical patients who attempt suicide
      and those who request assisted suicide. When the physical and psychological
      sources of the desperation that underlies requests for assisted suicide are
      addressed, the desire for death diminishes and patients are usually grateful for
      the time remaining to them. Improved psychiatric and medical care for those who
      are terminally ill offer significant possibilities for suicide prevention.

PMID- 10073388
TI  - The risk of suicide in patients with bipolar disorders.
AB  - Patients with bipolar disorder have a high risk of committing suicide, but
      determining the exact risk is complicated. For many years, the lifetime suicide
      risk in bipolar disorder was accepted as 15%, but recent researchers have
      suggested that the lifetime suicide risk may be lower. The group of bipolar
      patients at highest risk of suicide are young men who are in an early phase of
      the illness, especially those who have made a previous suicide attempt, those
      abusing alcohol, and those recently discharged from the hospital. The risk is
      also increased in patients who are in the depressed phase of bipolar illness, who
      have mixed states, or who have psychotic mania. Lithium prophylaxis appears to
      decrease suicide attempts.

PMID- 10073389
TI  - Suicide risk in patients with major depressive disorder.
AB  - Understanding the origins of suicide is the first step in preventing it. Review
      of the current literature has revealed only limited data from general practice
      and community samples; most research has been performed on inpatient psychiatric
      populations, and extended follow-ups are rare. Mood disorders were found to be
      highly associated with suicide, especially in patients with major depressive
      disorder. Depression is an important factor in suicides of adolescents and the
      elderly, but those with late-onset depression are at higher risk. Both
      comorbidity with other disorders, such as anxiety and agitation, and rapid
      changes in the depressive state, for instance after release from the hospital,
      increase the risk for suicide.

PMID- 10073390
TI  - Suicide attempts in major affective disorder patients with comorbid substance use
      disorders.
AB  - BACKGROUND: The widely accepted impression that substance abuse and dependence
      are associated with increased suicidal risk was evaluated by literature review
      and with new data. METHOD: Previous research on this association was reviewed,
      and clinical data on suicide attempts and substance use in 504 mood disorder
      patients hospitalized in 4 psychiatric units in Sardinia affiliated with the
      Italian mental health system were analyzed. RESULTS: The literature supports
      associations of alcohol and drug use comorbidity with major affective disorders,
      and of some substances (polyabuse, alcohol, heroin, cocaine, and even tobacco,
      but perhaps not marijuana or hallucinogens) with suicidal behavior. Our new
      findings generally supported these 2-way associations. Suicidal risks were
      similar in hospitalized men and women but were associated with bipolar II,
      bipolar I (mainly mixed), and unipolar depressive disorders as well as substance
      abuse, with little effect of type of agent. Substance abuse was more common in
      nonmixed bipolar disorders, men, and age below 30. CONCLUSION: The tendency for
      bipolar I, mainly nonmixed patients, to have a relatively high risk of substance
      abuse and low risk of suicide attempts indicates that mainly depressive or
      dysphoric (bipolar II, nonbipolar, and bipolar I, mainly mixed) mood disorders
      may be especially lethal. Differences in risks of substance abuse and suicidal
      behavior in men and in bipolar I patients further suggest that substance abuse
      and mood disorders may contribute to suicidal risk with at least partial
      independence or additivity.

PMID- 10073391
TI  - Methods of adolescent suicide prevention.
AB  - This article reviews a series of studies developed to address the public health
      problem of adolescent suicide. The clinical predictors of adolescent suicide are
      presented, and several related prevention strategies are offered and critiqued.
      The method of suicide prevention found to be most effective is a systematic,
      direct-screening procedure that has a high potential for institutionalization.

PMID- 10073392
TI  - Effects of lithium treatment and its discontinuation on suicidal behavior in
      bipolar manic-depressive disorders.
AB  - BACKGROUND: Whether mood-altering treatments reduce risk of suicidal behavior
      remains largely unproved. METHOD: We compared suicidal rates in published studies
      of patients treated with lithium with those who were not, and in a mood disorders
      clinic before, during, and after discontinuing lithium. RESULTS: Published
      reports indicate a 7.0-fold lower rate of suicidal acts with lithium treatment of
      manic-depressive patients. In new findings in over 300 bipolar patients, latency
      from illness onset to lithium maintenance averaged 8.3 years (from 11.0 years in
      women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but
      half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most
      acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states
      and were associated with previous severe depression, prior attempts, and lower
      age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold
      during lithium treatment, with 8.3-fold cumulative sparing of risk by 15 years on
      lithium. In the first year off lithium, affective illness recurred in 67% of
      patients, and suicidal rates rose 20-fold but were much lower thereafter;
      fatalities were 14 times more frequent after discontinuation of lithium. Early
      morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow
      versus rapid discontinuation. CONCLUSION: Lithium maintenance is associated with
      sustained reduction of suicidal acts in manic-depressive disorders. Treatment
      discontinuation, particularly abruptly, led to early affective morbidity and
      suicidal behavior. Improved diagnosis and treatment as well as earlier
      intervention for potentially lethal bipolar depression are urgently needed, as
      are studies of all mood-altering agents for effects on suicidal behavior.

PMID- 10073393
TI  - Lithium therapy and suicide risk.
AB  - BACKGROUND: Studies from the early 90s have suggested that patients selected for
      and compliant with treatment at specialized lithium clinics have lower-than
      expected suicide rates. The present study examines whether such findings can be
      replicated under less select treatment conditions. METHOD: All 362 patients in
      Goteborg, Sweden, with DSM-III-R mood or schizoaffective disorders, hospitalized
      at least once during an 8-year period and treated with lithium for a minimum of 1
      year, were followed. The study included 3911 patient-years on lithium and,
      because of permanent or temporary discontinuation, 1274 patient-years off
      lithium. RESULTS: The risk of suicide was significantly increased on (standard
      mortality ratio [SMR] = 6.1) as well as off lithium (SMR = 29.0), but the
      relative risk of suicide was 4.8 times higher during periods off lithium (p <
      .02; 95% confidence limits 1.1 to 12.6). Ongoing lithium treatment was associated
      with a 77% reduction in the risk of suicide, whereas alcohol or drug abuse was
      associated with a 284% increased risk. CONCLUSION: The findings suggest that
      ongoing lithium treatment is associated with a lower suicide risk. Whether this
      is due to lithium's mood-stabilizing properties, to lower suicide risk per se in
      the patients who remain in treatment, or to a specific antisuicidal effect of the
      lithium ion cannot be determined since patients were not randomized to
      discontinue treatment. This methodological shortcoming is shared with every study
      in the field. All results regarding the influence of lithium on suicide rates
      must therefore be interpreted with extreme caution.

PMID- 10073394
TI  - Anticonvulsant therapy and suicide risk in affective disorders.
AB  - Patients with major affective disorders are more likely to complete suicide than
      patients in any other medical group. Established risk factors for completed
      suicide in affective disorders include acute depression (with turmoil,
      hopelessness, global insomnia, anhedonia, anxiety and/or panic), mixed episodes,
      rapid cycling, substance abuse, aggression and/or impulsivity, low serotonergic
      activity, and hypothalamic-pituitary-adrenal axis activation. Although
      anticonvulsants have mood-stabilizing and antidepressant properties, few data are
      available on the antisuicide effects of anticonvulsant treatment in manic
      depressive patients. On the other hand, as reviewed elsewhere in this issue,
      massive data have been accumulated on the antisuicide effect of lithium. This
      article discusses lithium versus anticonvulsants in the prevention of suicide
      associated with affective disorders and future treatment strategies to reduce
      this most serious complication of manic-depressive illness.

PMID- 10073395
TI  - Antidepressants and suicidal risk.
AB  - Only 5% of suicidal patients on the average use their prescribed antidepressant
      to commit suicide. Underprescription of antidepressants and failure of
      antidepressant therapy appear to be of greater practical importance than the
      toxicity of individual compounds. Prescribing less toxic agents, therefore, will
      not be of great advantage, especially if they are less efficacious. Several
      antidepressants including the selective serotonin reuptake inhibitors (SSRIs) may
      increase suicidal behavior by energizing depressed patients to act along
      preexisting suicidal thoughts or by inducing akathisia with associated self
      destructive impulses. For acutely suicidal patients, the use of more sedating
      antidepressants is recommended. Clinical trials could not confirm a superiority
      of SSRIs over tricyclics in reducing the number of suicide attempts. There is
      evidence from large international data sources and a large multicenter controlled
      trial that lithium prophylaxis decreases the suicide risk and overall mortality
      in affective disorders. A suicide-preventing effect has not been demonstrated
      conclusively for antidepressants or non-lithium mood stabilizers.

PMID- 10073396
TI  - Do antipsychotic medications decrease the risk of suicide in patients with
      schizophrenia?
AB  - The lifetime risk of suicide in persons with schizophrenia is much greater than
      that in the general population. The role of antipsychotic medications in
      decreasing suicide risk in schizophrenia has been little studied, and results
      often appear inconclusive and even confusing when issues such as dose-response
      effect are examined. Yet, evidence exists that both the traditional and newer
      antipsychotic medications reduce the risk of suicide and suicide attempts in
      schizophrenia. Because side effects are potentially significant risk factors in
      suicide, considerable incentive exists to examine whether newer antipsychotic
      agents that have a lower incidence of extrapyramidal side effects offer greater
      safety for this population.

PMID- 10073397
TI  - Electroconvulsive therapy and suicide risk.
AB  - For major psychiatric disorders in which suicidality is often a symptom,
      electroconvulsive therapy (ECT) is an established, highly effective treatment. In
      fact, suicidal risk may be an indication for the use of ECT to treat those
      disorders. The authors present new data and review clinical experience that
      indicate that ECT often exerts a profound short-term beneficial effect on
      suicidality. Little, if any, evidence supports a long-term positive effect of ECT
      on suicide rates, especially if diagnostically heterogeneous groups are
      considered. However, patients may have been assigned ECT precisely because they
      were suicidal and, hence, these reports may represent underestimates. As a whole,
      the published reports are weakened by methodological shortcomings, such as lack
      of controls, weak design, and possible cohort effects. In fact, most studies were
      designed to examine the impact of ECT on mortality rates in general, and all but
      one study found reductions in overall mortality, the source of which remains
      undetermined.

PMID- 10073398
TI  - Effects of medical interventions on suicidal behavior. Summary and conclusions.
AB  - BACKGROUND: An international symposium evaluated current knowledge of the
      epidemiology, psychobiology, and effects of medical treatment on suicidal
      behavior. METHOD: Moderators summarized the main findings and conclusions of the
      participants on the basis of presentations and consensus statements at the
      meeting. RESULTS: Despite striking advances in the medical treatment of mood
      disorders in the past half-century, rates of suicidal acts have changed little in
      the general population. Evidence of reduction of long-term rates of suicidal acts
      in specific at-risk populations remains very limited, particularly persons with
      major affective illnesses and other common, primary or comorbid psychiatric and
      substance use disorders. It is plausible that reduction of psychiatric morbidity
      should limit suicidal risk, but very little is known about specific effects of
      most psychiatric treatments or other interventions aimed at suicide prevention.
      An exception is substantial evidence of lower suicidal risk during long-term
      lithium treatment that was not equaled with carbamazepine. However, diagnosis and
      timely therapeutic interventions reach only a minority of psychiatrically ill
      persons at risk for suicide. CONCLUSION: Renewed efforts are strongly urged to:
      (1) improve public and professional awareness of risk factors for suicide, (2)
      enhance earlier access to appropriate clinical assessment and increasingly safe
      and effective treatments for affective and psychotic disorders, and (3) encourage
      and support research to clarify specific benefits and risks of medical treatments
      and social interventions aimed at preventing suicide.

PMID- 10073399
TI  - Wilms' tumor. Introduction.

PMID- 10073400
TI  - Genetics of Wilms' tumor.
AB  - The molecular genetic characterization of Wilms' tumor has played a prominent
      role in advancing our knowledge of the genetic aspects underlying the development
      of cancer in general. Unlike the genetic mechanism leading to the development of
      retinoblastoma, an embryonal tumor of childhood affecting the retina, which only
      requires the inactivation of one single gene, the biological pathways leading to
      the development of Wilms' tumor are complex and likely involve several genetic
      loci. These include two genes on chromosome 11p; one on chromosome 11p13 (the
      Wilms' tumor suppressor gene WT1) and the other on chromosome 11p15 (the putative
      Wilms' tumor suppressor gene WT2). In addition to these two genes, loci at 1p,
      7p, 16q, 17p (the p53 tumor suppressor gene), and 19q (the putative familial
      Wilms' tumor gene FWT2) are also believed to harbor genes involved in the biology
      of Wilms' tumor. Herein these loci are reviewed and their clinical significance
      is summarized.

PMID- 10073401
TI  - Imaging of patients with Wilms' tumor.
AB  - Continued advances in imaging technology have improved the ability to detect
      Wilms' tumor and its precursor, nephroblastomatosis, as well as tumor spread to
      other organs in a less invasive manner than in years past. However, there is
      still wide variation in clinical practice in the imaging of this tumor compared
      with the guidelines set forth by the National Wilms' Tumor Study Group. This
      article reviews current imaging options and recommendations for the evaluation of
      children with Wilms' tumor as well as for surveillance of children with
      associated disorders such as hemihypertrophy.

PMID- 10073402
TI  - The role of preoperative chemotherapy for Wilms' tumor: the NWTSG perspective.
      National Wilms' Tumor Study Group.
AB  - Extensive experience has been accumulated with the use of preoperative therapy
      for children with Wilms' tumor. In selected cases, preoperative chemotherapy can
      reduce the morbidity of treatment. This is most appropriate for children with
      bilateral tumors in whom parenchymal sparing procedures are desirable. Patients
      with inoperable tumors and extensive intravascular tumor extension can also
      benefit from this approach. The NWTSG recommendations for preoperative
      chemotherapy in patients with Wilms' tumor are presented.

PMID- 10073403
TI  - The role of preoperative chemotherapy in the treatment of nephroblastoma: the
      SIOP experience. Societe Internationale d'Oncologie Pediatrique.
AB  - Treatment of Wilms' tumor is an example of success of modern oncology. A
      combination of surgery, radiotherapy, and chemotherapy is widely accepted as the
      efficacious treatment of nephroblastoma. However, timing of each part of the
      treatment differs, in various protocols: the Societe Internationale d'Oncologie
      Pediatrique (SIOP) recommends the diagnosis based on imaging and metabolic
      exclusion of neuroblastoma to reduce the biopsy-related risk of spillage. In
      patients more than 6 months old, the treatment starts with the preoperative
      chemotherapy to improve the stage distribution at surgery and decrease the
      complications rate. Patients with advanced nephroblastoma, as those with vena
      cava thrombus and lung metastases, can benefit the most from the pretreatment.
      Results from the SIOP studies 6 and 9 confirm these statements: the stage
      distribution after the pretreatment reveals more than 50% of cases staged I, the
      4-year disease-free survival in pulmonary stages IV was 83%, and of 42 patients
      with vena cava thrombus still present at surgery, 38 are alive from 27 to 109
      months.

PMID- 10073404
TI  - Surgical considerations for patients with Wilms' tumor.
AB  - Despite the advances in multimodal treatment of Wilms' tumor, surgical staging
      and tumor resection remain a central component of therapy. Although standard
      approaches are available through multicenter studies, such as the NWTS and SIOP,
      controversy exists regarding several aspects of surgical management. Recent data
      call into question the need for contralateral exploration in the era of modern
      imaging. Various methods are available for managing caval tumor thrombus.
      Bilateral Wilms' tumor requires a special surgical strategy. The surgeon plays a
      key role in determining whether preoperative chemotherapy should be used to
      facilitate surgical resection. The role of partial nephrectomy is still being
      defined. And finally, surgery plays an important role in the management of tumor
      recurrence. Surgeons must be fully aware of the data and philosophical issues
      that pertain to these areas if they are to fulfill their role in the
      multidisciplinary team caring for children with Wilms' tumor.

PMID- 10073405
TI  - Postoperative chemotherapy in the National Wilms' Tumor Studies.
AB  - There has been substantial improvement in survival in patients with Wilms' tumor
      over the last 30 years in the United States. This has been the direct result of
      the efforts of the National Wilms' Tumor Study Group. This group was established
      in 1969 through the conglomeration of pediatric divisions of two existing
      cooperative study groups for the purpose of accruing large enough patient
      populations to conduct meaningful clinical trials. Thus far, four National Wilms'
      tumor trials have been completed. The fifth study is currently accepting patients
      for treatment. This article reviews the remarkable success in the treatment of
      Wilms' tumor and the evolution of present day postoperative therapy.

PMID- 10073406
TI  - The role of radiation therapy in the management of Wilms' tumor.
AB  - Since the early decades of this century, radiation therapy has played an
      important role in the management of Wilms' tumor. Although in prior years the
      high radiation doses and eccentric field arrangements used in treatment were
      responsible for significant late toxicity, examination of long-term survivors and
      the important information obtained from the National Wilms' Tumor Studies (NWTS)
      and Societe Internationale d'Oncologie Pediatrique studies have now allowed us to
      tailor radiation fields and doses to provide high levels of local tumor control
      with minimal late effects. At present, most patients with NWTS stage III and
      stage IV tumors are offered radiotherapy as an integral component of their cancer
      management. Attempts to further refine selection criteria defining those patient
      groups who will benefit from radiation therapy are ongoing.

PMID- 10073407
TI  - Long-term complications and post-treatment follow-up of patients with Wilms'
      tumor.
AB  - An increasing number of children with Wilms' tumor can expect to be cured,
      reflecting the undisputed progress made in the treatment of children with this
      renal cancer. However, it does underscore the need to screen survivors for late
      effects of cancer therapy. Some of the late effects, such as those following
      radiation therapy, should be expected after a considerable latent period. Others,
      such as those occurring after the administration of certain chemotherapeutics
      agents, are commonly immediate, usually transient, but occasionally permanent.
      Although children seem to tolerate acute toxicities of therapy better than do
      adults, the growing child may be more vulnerable to the delayed adverse sequelae
      of cancer therapy, such as effects on growth, fertility, and neuropsychological
      function. This article reviews many of the late effects seen in survivors of
      Wilms' tumor and the way in which these effects relate to the different
      therapeutical modalities used (surgery, chemotherapy, and radiation).

PMID- 10073408
TI  - Predictive value of maternal-IgG avidity for congenital human cytomegalovirus
      infection.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is now the most common cause of viral
      intrauterine infection. Fetal damage is mostly linked to maternal primary
      infection. It is therefore important to differentiate primary from recurrent or
      persistent HCMV infection in pregnant females. For this purpose, IgM tests are
      not reliable enough and the measurement of the IgG avidity appears to be
      presently the best method. OBJECTIVE: To evaluate the performance of the
      measurement of HCMV-IgG avidity by a 8 M urea denaturation assay in predicting
      congenital infection in the offspring. STUDY DESIGN: Seventy-eight women were
      included in this study on the basis of a HCMV IgM positive or equivocal result on
      a first serum during pregnancy, but without a documented seroconversion history.
      The IgG avidity was measured and correlated with the outcome of the pregnancy.
      RESULTS: In eight cases of HCMV in utero infection the maternal HCMV-IgG avidity
      index was below 50%. One case of HCMV in utero infection was observed despite a
      high avidity index during the second trimester of the pregnancy. High or
      intermediate HCMV-IgG avidity indexes during the first trimester of pregnancy
      were not associated with a congenital infection. CONCLUSIONS: Even in the
      presence of an IgM positive result, an HCMV IgG avidity index above 65% on a
      serum obtained during the first trimester of pregnancy could reasonably be
      considered as a good indicator of past HCMV infection. In these conditions
      invasive prenatal diagnosis is not necessary.

PMID- 10073409
TI  - Typing of rabies virus isolates by DNA enzyme immunoassay.
AB  - BACKGROUND: Alternatives to antigenic typing are needed for epidemiologic surveys
      of the rabies virus associated with translocated coyotes and foxes, especially in
      areas where a closely related rabies virus is transmitted by striped skunks.
      OBJECTIVES: We developed and evaluated two enzyme based typing methods for rabies
      virus. The products of a reverse transcription-polymerase chain reaction (RT/PCR)
      of the nucleoprotein gene were hybridized to type specific probes and detected by
      enzyme assay after immobilization on microtiter plates. STUDY DESIGN: We tested
      RT/PCR products of 27 rabies isolates by two different DNA enzyme immunoassays
      (DEIA) and evaluated the quality of the results from the corresponding nucleotide
      sequence of the samples. RESULTS: Using a set of two probes, one of the DEIAs
      correctly identified 26/27 samples as variants of rabies virus associated with
      either skunks, foxes, or coyotes. The identity of one fox rabies sample was
      unresolved by this assay. The second DEIA correctly identified 24/27 samples as
      variants of rabies virus associated with either skunks, foxes, or coyotes. This
      assay did not resolve the identity of two fox rabies samples, and misidentified
      one fox rabies sample as a skunk rabies sample. CONCLUSIONS: DEIA can be used for
      epidemiologic studies of variants of rabies virus associated with skunks, foxes,
      and coyotes. Both DEIA methods were effective when typing probes recognized
      changes at a minimum of two nucleotide positions between variants, but only one
      assay method was sufficiently stringent to detect a single base pair mismatch.
      The inherent mutability of RNA viruses must be considered when designing and
      evaluating typing methods.

PMID- 10073410
TI  - IgM antibodies in hospitalized children with febrile illness during an inter
      epidemic period of measles, in Somalia.
AB  - BACKGROUND: In the context of the measles elimination programme, endorsed by the
      expanded programme on immunization of the World Health Organization, the
      identification of infections which may be confused with measles is a major
      challenge. OBJECTIVE: To determine the causes of febrile illness in children in
      an inter-epidemic period of measles in a Somalian hospital. STUDY DESIGN:
      Serological tests were performed on sera from 23 Somali children with febrile
      illness and from 23 age matched children, to measure the specific IgM and IgG
      antibodies against measles virus, mumps virus, rubella virus, human herpes-6
      virus, Epstein Barr virus, parvovirus B19, dengue virus, Mycoplasma pneumoniae
      and Rickettsia conorii. RESULTS: In about one third of the cases of febrile
      illness viral, mycoplasmal and rickettsial agents could be identified
      serologically as the probable cause of the disease. CONCLUSIONS: Although febrile
      illness with rash in children needing hospitalization is usually assumed to be
      due to measles, there are several other important virological causes of this
      condition which need to be considered in the differential diagnosis. Moreover
      there is a growing need to develop a simple, sensitive, specific and ready to use
      test to identify each case of measles, if this disease is to be eliminated.

PMID- 10073411
TI  - Anti-HIV-1 seroreactivity and HIV transmission route[R1]. The HEC/FIOCRUZ AIDS
      Clinical Research Group.
AB  - BACKGROUND: Antibody binding assays carried out by our group have consistently
      indicated a higher reactivity of sera from male HIV-1 infected individuals. This
      study was carried out in order to analyze the importance of gender, route of
      transmission, disease progression and HIV-1 genotype in seroreactivity assays.
      STUDY DESIGN: Specificity of antibody binding was studied in plasma of 247 HIV-1
      seropositive individuals belonging to patient groups of pregnant women, injecting
      drug users (IDUs) and recent seroconvertors, resident in Rio de Janeiro, RJ.
      Recognition of synthetic peptides corresponding to antigenically important
      epitopes in the envelope of HIV-1 (gp41 immunodominant epitope, V3 loop, V2 loop
      and gp41 735-752 epitope) was determined. RESULTS: The immunodominant gp41
      peptide (amino acids 594-613, HIV-1 MN sequence) was recognized by 85% of all
      plasma tested. Reactivity with the gp41 735-752 peptide and gp120 V2 loop
      peptides was low but quite variable, being generally more often specific to a
      Brazilian V2 peptide used than to the HIV-1 MN derived V2 peptide. The overall
      recognition of the different V3 peptides tested varied from 41 to 76%. Patients
      with more advanced disease showed a more frequent reactivity with the peptides
      studied than did asymptomatic patients. Statistically significant differences in
      peptide recognition were observed by multiple logistic analyses comparing plasma
      derived from individuals infected by blood or sexual HIV transmission, adjusting
      for disease progression and gender. Plasma from individuals infected by sexual
      transmission showed lower peptide recognition than did plasma from individuals
      infected through HIV positive blood. Association attempts between seroreactivity
      and genotype indicated that plasma derived from patients infected with HIV-1 of
      the F subtype showed highest recognition of heterologous V3 peptides, as well as
      a slightly more frequent recognition of the non-V3 peptides tested. Recognition
      of homologous peptides was generally higher than recognition of heterologous
      peptides. Differences were most pronounced between the prototypical HIV-1 B
      subtype and the Brazilian B" variant of this subtype but almost non-existent
      between the HIV-1 B and F subtypes. CONCLUSIONS: Individual gender was shown to
      be a confounder when investigating the relationships of peptide reaction to HIV-1
      route of transmission through multivariate statistical methods: patients infected
      by blood transmission (IDU) present higher frequency of peptide recognition than
      individuals infected by sexual HIV-1 transmission. Plasma from individuals
      infected with the B" variant (GWG) of B subtype HIV-1 showed lower heterologous
      peptide recognition than that from HIV-1 B (GPG) or F infected individuals.

PMID- 10073412
TI  - Evolution of the HIV epidemic in Kaliningrad, Russia.
AB  - BACKGROUND: Our earlier epidemiological and virological analysis made in 1997
      suggested that in the Kaliningrad region of Russia a rapidly spreading human
      immunodeficiency virus (HIV)-epidemic among injecting drug users had recently
      started and that it was caused by an unusual A/B subtype recombinant strain of
      HIV. Furthermore, it was evident that the societal and health care structures
      necessary to combat the spread of the infection were not well developed. Since
      June 1996 more than 2400 HIV-infections have been detected in the region with a
      population of less than 1 million. Here we report the current situation
      concerning the epidemic and its risk factors. The information is based on
      information collected during several visits and from written reports. OBJECTIVES:
      Whereas almost all cases in the earliest phase of the epidemic have occurred
      among injecting drug users (IDU), sexual transmission may soon become more common
      and spread the epidemic into the non-IDU population. We describe here the recent
      evolution of the epidemic and the various risk factors that seem to contribute to
      the outbreak. We also describe the current resources that are used for
      prevention. STUDY DESIGN: Information complementing earlier studies were
      collected during visits to Kaliningrad from direct observations, interviews with
      local authorities and official bulletins and written reports by local and
      national experts. CONCLUSIONS: Local resource building with the aid of
      international help is urgently needed to alleviate the forthcoming crisis due to
      clinical consequences of AIDS. Both prevention and patient management require
      resources that are not available at present. Also, more virological studies
      should be undertaken to identify the present and future pattern of the epidemic.

PMID- 10073413
TI  - Adaptation of human enteric coronavirus to growth in cell lines.
AB  - BACKGROUND: The existence of human enteric coronavirus (HEC) has been debated
      since its first description in stool by electron microscopy (EM) in 1975. Needed
      to resolve the issue is its cultivation in readily available cell lines.
      OBJECTIVES: To grow HEC in cell lines. To describe its characteristics and to
      differentiate it from other human and animal coronaviruses. STUDY DESIGN:
      Originally grown in human fetal intestinal organ culture, HEC was passed in J774
      cells (a mouse macrophage cell line) and C6/36 cells (a mosquito cell line). Its
      cytopathic effect (CPE) and pattern of immunofluorescence were described. Its
      appearance was ascertained by negative staining and transmission EM. Its
      structural proteins were delineated by polyacrylamide gel electrophoresis (PAGE)
      and Western blotting (WB). The antigenic character of the virus was determined by
      immunofluorescence and WB. Agglutination with mouse erythrocytes was performed.
      RESULTS: In J774 cells, HEC induced the formation of giant cells and small
      syncytia. Immunofluorescence in both J774 and C6/36 cells was limited to the
      cytoplasm. Studies with transmission EM revealed the virus to have the typical
      appearance of other coronaviruses, to be 80-120 nm in diameter, and to bud into
      cysternae of the endoplasmic reticulum. By PAGE and WB, its major protein has an
      average molecular weight (MW) of 41 kilodaltons (kDa). Two other proteins had MWs
      of 190 and 24 kDa. By immunofluorescence and WB, HEC is antigenically distinct
      from human coronaviruses 0C43 and 229E and mouse hepatitis virus (A59 strain).
      Preparations of HEC did not agglutinate mouse erythrocytes. CONCLUSION: We
      conclude that HEC is a human coronavirus that is antigenically unrelated to 0C43
      and 229E viruses. Growth of HEC in readily available cell lines should aid in
      elucidating its role as a pathogen in human diarrheal illnesses.

PMID- 10073414
TI  - Prevalence of herpes simplex virus types 1 and 2, cytomegalovirus, and varicella
      zoster virus infections in Eritrea.
AB  - BACKGROUND: Herpesviruses establish latent infections in their hosts for life.
      The scarcity of data that exists in regard to herpesvirus infections in many
      African regions, could partly be due to the mild nature of their primary
      infections and the lack of means for their proper diagnosis. However, in recent
      decades the alarming spread of HIV infection in Africa and associated frequent
      reactivation of herpesvirus infections is leaving less room for neglect. This
      seroprevalence study is intended to help in the evaluation of the prevalence of
      herpesvirus infections in Eritrea. OBJECTIVE: To evaluate the spread of herpes
      simplex virus types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), and
      varicella-zoster virus (VZV) infections. STUDY DESIGN: The study population
      groups comprise female sex workers (FSW), former guerrilla fighters, truck
      drivers, port workers, a tribe called Rashaida, pregnant women, children under 5
      years of age, and children over 5 years of age. The groups of pregnant women and
      children under and over 5 years of age were included to form a background for the
      evaluation of groups considered at risk for sexually transmitted or blood borne
      infections. RESULTS: All study groups had a high seroprevalence of HSV-1
      infections ( > 80%), except for the children under 5 years of age. The FSW had
      the highest prevalence of HSV-2 infections, 80%, followed by guerrilla fighters,
      truck drivers, port workers, pregnant women, children, and the Rashaidas.
      Positivity for antibodies against CMV was > 90% in all studied populations. The
      prevalence of VZV infections was surprisingly low in the tribe of Rashaida, 44%
      compared to more than 90% in the other adult groups tested for VZV (P = 0.0001).
      CONCLUSION: The study shows that the prevalence of HSV-2 in the risk group of FSW
      was high, which could partly be explained by their sexual behaviours. HSV-2 was
      particularly low in the Rashaida group and, as expected, in the children. The low
      prevalence of VZV observed in the Rashaida is of importance since it makes them
      vulnerable to infection with varicella during their inevitable integration with
      the other tribes in their society.

PMID- 10073415
TI  - Evaluation of ELVIS HSV ID/Typing System for the detection and typing of herpes
      simplex virus from clinical specimens.
AB  - BACKGROUND: Herpes simplex virus (HSV) is a common pathogen with two serotypes:
      HSV-1 and HSV-2. HSV infection does not pose much of a threat to an
      immunocompetent host but to an immunocompromised host or a neonate the infection
      can be fatal. The Enzyme-Linked Virus Inducible System (ELVIS) employs a
      genetically altered baby hamster kidney (BHK) cell line that allows for the rapid
      overnight detection of HSV but also includes an immunofluorescent stain for the
      simultaneous detection and typing of HSV-1 and HSV-2. OBJECTIVE: To evaluate the
      ELVIS HSV ID/Typing System in comparison with HSV identification and typing in
      primary rabbit kidney (PRK) cells grown in shell vials. STUDY DESIGN: Over a
      period of 6 weeks, 130 specimens were submitted to the diagnostic virology
      laboratory and cultured for the presence of HSV. Two PRK shell vials and one
      ELVIS BHK shell vial were inoculated with patient specimen. PRK shell vials were
      observed for cytopathic effect (CPE) for up to 4 days. When CPE was observed the
      PRK shell vials were fixed and one shell vial was stained with HSV-1 monoclonal
      antibody (Mab) and the other was stained with HSV-2 Mab. The coverslips were
      observed under the fluorescent microscope for specific apple-green fluorescence.
      The BHK shell vials were incubated overnight, fixed, and stained with
      galactopyranoside (X-Gal). If blue cells were present, the specimen was positive
      for HSV. The coverslip was then observed under the fluorescent microscope for the
      presence of specific apple-green fluorescence, indicating HSV-2. If no specific
      apple-green stain was observed, the coverslip was stained with a fluorescent
      conjugated goat anti-mouse IgG to determine the presence of HSV-1. RESULTS: Of
      the 130 specimens, PRK shell vials detected 43 positive HSV; 30 were HSV-2 and 13
      were HSV-1. The ELVIS BHK shell vials detected 42 positive HSV; 30 were HSV-2 and
      12 were HSV-1. One low titer specimen was not identified as being HSV positive.
      Two specimens were not directly typed by the ELVIS system. One specimen had only
      one blue cell present and did not show specific staining for either HSV-1 or HSV
      2. The other specimen had only five blue cells present and only one fluorescent
      cell present that was difficult to type. As suggested by the manufacturer's
      instructions, both specimens that were not directly typed were re-grown overnight
      from their supernatants and were correctly identified and typed. CONCLUSION: The
      ELVIS HSV ID/Typing System is a rapid, highly specific and sensitive method of
      overnight HSV detection and typing.

PMID- 10073416
TI  - Variations in HIV-RNA viral load and CD4 counts of infants and children receiving
      antiretroviral drug therapy.

PMID- 10073417
TI  - Influence of glutathione on zinc-mediated cellular toxicity.
AB  - The effect of zinc on various pulmonary cell lines has been studied by measuring
      the depletion of total cellular glutathione after exposure to zinc(II) chloride
      at different concentrations. Total cellular glutathione (cGS) was measured at
      31+/-3 nmol/mg, 3.8+/-0.6 nmol/mg, and 3.7+/-1.2 nmol/mg protein in A549, L2, and
      11Lu cells, respectively. After treatment with buthionine sulfoximine (BSO), the
      cGS levels decreased by 20% in A549 cells and below 0.2 nmol/mg in L2 and 11Lu
      cells. Exposure of A549 cells to 25-200 microM ZnCl2 for 4 h alone decreased the
      cGS content to 60-80%. There was little additional effect in BSO-pretreated
      cells. In L2 and 11Lu cells, the decrease of cGS was 70-85% following exposure to
      15-150 microM ZnCl2 for 2 h. If BSO was also used, the decrease in cGS was 85-95%
      in L2 cells and 75-85% in 11Lu cells. Exposure to 25-250 microM ZnCl2 for 2 h
      diminished protein synthesis as determined by radiolabeled methionine
      incorporation, with half-maximum inhibition (EC50) from 40-160 microM ZnCl2. To
      attain similar EC50 values in BSO-pretreated cells, only about half the zinc
      concentrations were required as compared to cells without pretreatment. The
      decrease of cGS was accompanied by an increased ratio of oxidized: reduced
      glutathione that was more pronounced in cells with low glutathione content.

PMID- 10073418
TI  - Determination of total arsenic concentrations in nails by inductively coupled
      plasma mass spectrometry.
AB  - The analysis of trace elements in biological samples will extend our
      understanding of the impact that environmental exposure to these elements has on
      human health. Measuring arsenic content in nails has proven useful in studies
      evaluating the chronic body burden of arsenic. In this study, we developed
      methodology with inductively coupled plasma-mass spectrometry (ICP-MS) for the
      determination of total arsenic in nails. We assessed the utility of the washing
      procedures for removing surface contamination. Four types of preanalysis
      treatments (water bath, sonication, water bath plus sonication, and control)
      after sample decomposition by nitric acid were compared to evaluate the digestion
      efficiencies. In addition, we studied the stability of the solution over 1 wk and
      the effect of acidity on the arsenic signal. Arsenic content in the digested
      solution was analyzed by using Ar-N2 plasma with Te as the internal standard. The
      results suggest that washing once with 1% Triton X-100 for 20 min for cleaning
      nail samples prior to ICP-MS analysis is satisfactory. Repeated measurement
      analysis of variance revealed that there was no significant difference among the
      various sample preparation techniques. Moreover, the measurements were
      reproducible within 1 wk, and acidity seemed to have no substantial influence on
      the arsenic signal. A limit of detection (on the basis of three times the
      standard deviation of the blank measurement) of 7 ng As/g toenail was achieved
      with this system, and arsenic recoveries from reference materials (human hair and
      nails) were in good agreement (95-106% recovery) with the certified/reference
      values of the standard reference materials. ICP-MS offers high accuracy and
      precision, as well as high-throughput capacity in the analysis of total arsenic
      in nail samples.

PMID- 10073419
TI  - Ultrastructural and trace metal studies on radiographers' hair and nails.
AB  - Scalp hair and fingernail samples of 42 medical radiographers and 42
      nonradiographers (control) with matching age groups and food habits were
      collected for this study. Trace metal estimation by atomic absorption
      spectrometry (AAS) has indicated a significant increase (P < 0.001) in Zn, Cu,
      and Cd contents in the radiographers' hair and nails. Scanning electron
      microscopy (SEM) revealed structural changes in the hair and nails of
      radiographers. Significant alterations in the Zn and Cd contents along with
      extensive structural damage in the hair and nails probably indicate that low-dose
      X-radiation imposes stress on these radiation workers.

PMID- 10073420
TI  - Combined effect of high-fat diet and copper deficiency during gestation on fetal
      copper status in the rat.
AB  - We have previously shown that a low-copper (Cu) diet produced alterations in
      placental Cu transport and fetal Cu stores. Because Cu deficiency has been
      associated with lipid deposition in rat dam liver, we hypothesized that a high
      fat intake, a prevalent dietary habit in many populations, may worsen fetal Cu
      status and its closely linked iron (Fe) deposits. Pregnant rats were fed one of
      four diets during the second half of gestation: NFNCu: normal fat (7%), normal Cu
      (6 mg/kg); HFNCu: high fat (21%), normal Cu; NFLCu: normal fat, low Cu (0.6
      mg/kg), and HFLCu: high fat, low Cu. One day before delivery, dams were
      anesthetized, and maternal as well as fetal plasma and tissues were obtained.
      Maternal, fetal, and placental weights were indistinguishable regardless of the
      group. Dam plasma Cu and placental Cu were lower in both LCu groups than in the
      NFNCu or the HFNCu groups. However, fetal plasma Cu was similar in all treatment
      groups. Dam and fetal liver Cu stores were reduced in the LCu groups compared to
      the NCu groups. This resulted in lower fetal/maternal liver Cu ratios in the
      NFLCu (1.79+/-0.14, p < 0.05) and HFLCu (1.59+/-0.21, p < 0.05) as compared to
      the NFNCu (4.12+/-0.44) and the HFNCu (4.15+/-0.27). Dam liver Fe was higher in
      the NFNCu than in HFNCu group (1.10+/-0.8 vs. 0.89+/-0.06 micromol/g, p < 0.05);
      fetal liver Fe from HFNCu and NFLCu dams was lower than that from NFNCu fetuses
      (NFNCu: 2.42+/-0.14; HFNCu: 1.92+/-0.15, p < 0.05; NFLCu: 1.81+/-0.10, p < 0.01).
      Fetuses of the HFLCu group had a lower heart Fe than the NFNCu group (0.56+/-0.03
      vs. 44.0+/-3.0 microg/g, p < 0.01). These data indicate that a maternal high-fat
      diet can potentially aggravate the effects of Cu deficiency by further altering
      fetal Cu and Fe tissue stores.

PMID- 10073421
TI  - Thyroid functions in lithium-treated psychiatric patients: a cross-sectional
      study.
AB  - In the present cross-sectional study, thyroid functions (viz. thyroid radioiodine
      uptake [RAIU] and serum T3, T4, and thyroid-stimulating hormone [TSH]) were
      evaluated in 24 healthy controls and 132 outdoor affective disorder patients.
      Eleven of these patients were to receive lithium (Li) and the remaining 121
      patients were at different stages of Li treatment ranging from 0.7 to 240 mo.
      RAIU was found to increase significantly throughout the Li therapy and was
      associated with the corresponding rise in TSH levels. In totality, Li treatment
      induced subclinical hypothyroidism in 51/132 (39%) of patients. However, 8/51
      patients who belonged to known iodine-deficient belt had abnormally high TSH
      (range 15.2-76.0 microIU/mL), low T4 (5.3+/-2.5 microg/dL), and normal T3 and at
      least 4 of these 8 patients were clinically hypothyroid. T4 levels declined
      significantly (p < 0.05) with Li treatment ranging from 61 to 240 mo as compared
      to the corresponding values in the pre-Li group. The T3/T4 ratio was found to be
      significantly higher with Li treatment ranging from 0.7 to 6 mo in comparison
      with the pre-Li group and this value returned to base levels after long-term Li
      therapy. High T3 and T4 were observed in 13% and 12% of the patients,
      respectively, as compared to the corresponding control values.

PMID- 10073422
TI  - Age-independent constancy of mineral contents in human ribs.
AB  - On age relationships of mineral contents in human bones, the contents of the
      sixth rib and a piece of its compact bone were determined by inductively coupled
      plasma atomic emission spectrometry (ICPS). The ribs were resected from 21
      subjects (14 men and 7 women) who died in age ranging from 65 to 93 yr. There
      were no age-dependent decreases in Ca and P contents of the ribs in the age range
      on ICPS. It was found that there were no age-dependent decreases in Ca and P in
      compact bones of ribs.

PMID- 10073423
TI  - Silicon bioavailability studies in young rapidly growing rats and turkeys fed
      semipurified diets: a comparative study.
AB  - Two experiments were conducted using completely randomized designs to study the
      bioavailability of Si from three sources to growing rats and turkeys fed
      semipurified diets. The basal diets were dextrose-egg albumin for rats and
      dextrose-casein for turkeys. The Si sources were tetraethylorthosilicate (TES),
      sodium silicate (NaSil), and sodium zeolite A (NaZA). Rats and turkeys were
      supplemented at 500 and 270 ppm Si, respectively, from each source. A control
      group of unsupplemented rats and turkeys was included in each experiment. In
      general, irrespective of Si source, Si supplementation slowed (p < 0.05 or p <
      0.01) growth rates in both rats and turkeys. Although dietary Si supplementation
      reduced (p < 0.05) plasma Mg levels and liver Zn concentrations in rats, it
      increased (p < 0.05) plasma P and reduced (p < 0.05) plasma Cu levels in turkeys.
      Rats on TES had significantly slower (p < 0.05 or p < 0.01) growth rates (5-10%)
      than those on NaSil or NaZA. In rats, NaZA and TES reduced (p < 0.05) hemoglobin
      concentrations and plasma Zn, respectively. However, plasma Mg levels were higher
      (p < 0.05) in TES than NaSil- or NaZA-fed rats. The source of the dietary Si did
      not affect (p < 0.05) the organ weights of rats and their mineral concentrations.
      Turkeys on TES diets grew at a significantly faster (p < 0.05) rate (15%) than
      those on NaSil or NaZA diets during the first 2 wk of experimentation. However,
      after 4 wk, there were no significant(p > 0.05) differences in growth between the
      Si sources. In turkeys, NaZA increased (p < 0.05) hematocrit levels and plasma Mg
      levels. Turkeys on NaZA diets had larger (p < 0.05) hearts and livers than those
      on NaSil but not TES. Liver Mn content was higher (p < 0.05) in turkeys on NaSil
      than TES or NaZA. Heart Zn was lower (p < 0.05) in turkeys on NaSil than TES, but
      not NaZA.

PMID- 10073424
TI  - Influence of transition metal ions on NMR proton T1 relaxation times of serum,
      blood, and red cells.
AB  - The spin-lattice relaxation rates (1/T1) of serum, whole blood, and red cells
      were measured vs several concentrations of transition metal ions. For comparative
      purposes, the similar experiments were repeated in water. The rates show a linear
      dependence on concentration of each ion for water, but nearly a linear dependence
      for blood and its constituents. The influence of each ion on 1/T1 in a sample was
      expressed by the slope (relaxivity) of the least-squares fitting of 1/T1 vs ion
      concentration. The relaxivities of Mn(II) in serum and of Fe(III) in serum and
      blood are greater than those in water, whereas the relaxivities of these ions in
      the other cases and of all the other ions in call cases are smaller than those in
      water. However, the relaxivity data show that Cr(III) in serum and blood affects
      the 1/T1 rates. The ratio of relaxivity of each sample to that of water is known
      as proton relaxation enhancement (PRR) factor (epsilon). The epsilon factors for
      present data suggest that the added ions are bound to proteins, and only Mn(II)
      in serum and Fe(III) in blood and serum are accessible to water.

PMID- 10073425
TI  - Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature
      review.
AB  - The purpose of this report is to review the efficacy and safety of vigabatrin in
      the treatment of infantile spasms in infants suffering from tuberous sclerosis
      complex. We reviewed all studies published in the English-language literature
      investigating the use of vigabatrin in the treatment of infantile spasms. Ten
      studies gave results for the efficacy of vigabatrin in infantile spasms for
      infants both with and without underlying diagnoses of tuberous sclerosis. Of the
      313 patients without tuberous sclerosis complex, 170 (54%) had complete cessation
      of their infantile spasms; of the 77 patients with tuberous sclerosis complex, 73
      (95%) had complete cessation of their seizures. We conclude that vigabatrin
      should be considered as first-line monotherapy for the treatment of infantile
      spasms in infants with either a confirmed diagnosis of tuberous sclerosis or
      those at high risk, ie, those with a first-degree relative with tuberous
      sclerosis complex. Paradoxically, in those without tuberous sclerosis complex,
      vigabatrin might be less efficacious than suggested by studies including patients
      with tuberous sclerosis complex.

PMID- 10073426
TI  - Progressive dystonia in a child with chromosome 18p deletion, treated with
      intrathecal baclofen.
AB  - We report a case of dystonia with a partial deletion of the short arm (p) of
      chromosome 18 and androgen insensitivity. Neurologic findings in the 18p syndrome
      are reported to include mental retardation, seizures, incoordination, tremor, and
      chorea. A 15-year-old girl with a denovo 18p deletion [karyotype 46, XY, del
      (18)(p11.1)] developed progressive asymmetric dystonia. She had oromotor apraxia
      and partial expressive aphasia since childhood, and she was able to partially
      communicate through elementary sign language. At the age of 15 years, she
      developed subacute and progressive choreic movements of the right arm, severe
      dystonic posturing of the left arm, and spastic dystonia in both legs. Her
      response to parenteral or oral benzodiazepines, oral trihexyphenidyl, benztropine
      mesylate, baclofen, and L-dopa were brief and inadequate. The response to
      intrathecal baclofen has been sustained over 18 months. In all likelihood, the
      18p deletion syndrome affecting this patient is significant in the pathogenesis
      of her acquired dystonia. Chronic intrathecal baclofen therapy via pump has been
      effective in this case and should be considered as a treatment modality in
      carefully selected patients with dystonia.

PMID- 10073427
TI  - Hemispheric language dominance in children demonstrated by functional magnetic
      resonance imaging.
AB  - The objective of this study was to demonstrate hemispheric language dominance in
      normal children. Fifteen normal children were evaluated with functional magnetic
      resonance imaging (MRI) using an age-related silent word spelling paradigm. The
      data were analyzed with the cross-correlation method, and lateralization indices
      were calculated in language regions as determined by Talairach coordinates.
      Activation foci were detected in the left inferior frontal area and were strongly
      lateralized, with language lateralization indices of 0.74 +/- 0.21 (age 7-12
      years, nine subjects), and 0.79 +/- 0.18 (13-18 years, six subjects). The indices
      were similar to those for adults (0.83 +/- 0.21, four subjects). Our study
      established that language is strongly lateralized to the left hemisphere in
      children as young as 7 years of age.

PMID- 10073428
TI  - Sturge-Weber disease: facial features of pediatric neurologic syndromes.

PMID- 10073429
TI  - Cardiac manifestations of congenital fiber-type disproportion myopathy.
AB  - Cardiac involvement has not been a reported feature of congenital fiber-type
      disproportion myopathy. We describe two children, aged 13 years and 1 year,
      respectively, who presented with serious cardiac symptomatology in conjunction
      with congenital fiber-type disproportion. One child developed dilated
      cardiomyopathy and medically intractable congestive heart failure necessitating
      cardiac transplantation at the age of 13 years. The second (unrelated) child
      developed atrial fibrillation with rapid atrioventricular conduction requiring
      treatment with digoxin. Skeletal muscle biopsy findings in both children showed
      congenital fiber-type disproportion with no evidence of a structural, dystrophic,
      or metabolic myopathy. Adenosine triphosphatase (ATPase) reacted sections showed
      type I hypotrophy with a predominance of type I fibers, confirmed by histogram
      analysis. Examination of the heart from patient 1 at the time of transplantation
      confirmed dilated cardiomyopathy with hypertrophic myocardiocytes. Although
      cardiomyopathy is commonly associated with other childhood myopathies, to our
      knowledge it has not been a feature in reported cases of congenital fiber-type
      disproportion. We recommend close cardiac assessment, with annual
      electrocardiograms, of children with congenital fiber-type disproportion.

PMID- 10073430
TI  - Asymmetries in brain maturation and behavioral disturbances: multivariate
      electroencephalogram and P300 studies.
AB  - If behavior results from brain function, some evidence of dysfunction could be
      expected in children with major behavioral problems. Yet, neurophysiologic
      studies in these children are frequently normal. We hypothesized a relationship
      between maturational asymmetry and behavior, given the role of hemispheric
      imbalance in adult psychopathology. The purpose of this study was to investigate
      whether age-sensitive neurophysiologic measures could identify behaviorally
      relevant maturational asymmetries in otherwise healthy children. Ninety-five
      children were studied; reasons for testing were behavioral (19), academic (12),
      medical nonneurologic (16), and mixed (28), along with 20 control subjects.
      Academic, behavioral (Child Behavioral Checklist), and psychometric (Wechsler
      Intelligence Scale for Children-Revised; WISC-R) measures were analyzed in
      relation to four neurophysiologic parameters: P300 Latency, P300 Latency
      Asymmetry, Maturational Z-score, and Maturational Z-score Asymmetry, within a
      canonical design. The highest correlation was behavior with Maturational Z-score
      Asymmetry. Academic scores were predicted by the three-variable interaction of
      P300 Latency,Maturational Z-score, and Maturational Z-score Asymmetry. We
      concluded that behavior was strongly influenced by maturational asymmetry, while
      academic performance depended on both global maturation and maturational
      asymmetry. Our results suggest that behavioral disturbances can have a neural
      substrate despite apparently normal electroencephalograms (EEGs) and event
      related potentials (ERPs). They open the possibility for specific therapeutic
      interventions to improve behavior and performance, and, perhaps, prevent major
      psychopathology in later life.

PMID- 10073431
TI  - Gender differences in the human cerebral cortex: more neurons in males; more
      processes in females.
AB  - This study's objective was to investigate morphometric gender differences of the
      cerebral cortex in six males and five females, 12 to 24 years old. Though human
      brains lack sexual dimorphism on routine neuropathologic examinations, gender
      specific brain weight, functional, and morphologic differences exist, suggesting
      that cortical differences may be found. Yet the cerebral cortex may be exempt
      from gender differences, as demonstrated by the fact that normal males and
      females perform comparably on intelligence tests. Stereologic morphometry on
      standardized histologic sections from 30 bilateral cortical loci determined
      cortical thickness, neuronal density, and derived neuronal number estimates. The
      mean +/- SD cortical thickness of the 60 loci examined was similar in males and
      females with right and left hemispheric gender ratios being balanced. In
      contrast, the average neuronal density of the same 60 loci was significantly
      higher in the male group than in the female group, and the corresponding mean
      male-to-female ratios were 1.18 in the right and 1.13 in the left hemisphere,
      which differ significantly from each other and from the balanced cortical
      thickness ratios. Estimates of neuronal numbers -- the product of neuronal
      thickness times density -- were 13% higher in males than in females, with mean
      male-to-female ratios of 1.13 in both hemispheres. The data provide morphologic
      evidence of considerable cerebral cortical dimorphism with the demonstration of
      significantly higher neuronal densities and neuronal number estimates in males,
      though with similar mean cortical thickness, implying a reciprocal increase in
      neuropil/neuronal processes in the female cortex.

PMID- 10073432
TI  - Partial seizures with focal epileptogenic electroencephalographic patterns in
      three related female patients with fragile-X syndrome.
AB  - Epilepsy and abnormal electroencephalographic (EEG) patterns have been reported
      in mentally retarded males with fragile-X syndrome, but the high incidence of
      epilepsy in such persons has been recognized only recently. These individuals
      have focal spikes in the EEG similar to the benign rolandic pattern. Female
      carriers have very rarely been reported to have epilepsy or nonspecific abnormal
      EEG patterns. We report partial seizures with a focal epileptogenic EEG pattern
      in two sisters and their grandmother, who are all carriers of fragile-X syndrome.
      The sisters have mild developmental delay, but the grandmother is of normal
      intelligence. The mother of the two sisters is known to be a carrier of the
      fragile-X chromosome and is of normal intelligence, with no history of seizures.
      It is important for physicians to be aware of the possibility that females
      presenting with partial seizures of unknown cause may be fragile-X carriers, and
      enquiry for a family history of intellectual disability should be pursued.

PMID- 10073433
TI  - Posterior fossa malformations and epilepsy.
AB  - The association between posterior fossa malformations and epilepsy is rarely
      reported in the literature. We describe 54 cases with posterior fossa
      malformations, according to embryogenesis classification, divided into two groups
      on the basis of presence or absence of epilepsy. Epilepsy occurred in 22 cases
      (40.7%) and was not related to the type of posterior fossa malformation or to
      supratentorial cerebral lesions associated with the malformation. Familial
      antecedents for epilepsy and/or febrile convulsions influenced the presence of
      epilepsy in patients with posterior fossa malformations (P < .01). Epilepsy was
      mainly partial (77.3%); benign partial/generalized epilepsies and febrile
      convulsions occurred in 27.3% of cases. Seizures disappeared for 2 or more years
      at the end of follow-up in 36.4% of patients. Good epilepsy prognosis was not
      related to the age at onset of seizures, familial antecedents for epilepsy and/or
      febrile convulsions, supratentorial associated lesions, or age of patients at the
      last observation. Profound mental retardation prevailed in patients with epilepsy
      (P < .01), as did pathologic electroencephalograms (EEG) (P < .0001), with
      paroxysmal abnormalities (P < .001) and asymmetry (P < .01). In our 54 cases of
      posterior fossa malformation, we identified two risk factors for epilepsy:
      familial antecedents for epilepsy and/or febrile convulsions and the involvement
      of the cerebellum in the malformation.

PMID- 10073434
TI  - Language disorders in Landau-Kleffner syndrome.
AB  - In the present long-term study, we analyzed language disorders in four patients
      with Landau-Kleffner syndrome. Their common first symptoms were disability in
      understanding spoken words, followed by inarticulation and a decreased amount of
      speech. All patients showed auditory verbal agnosia to some degree at some stage
      of their illness. However, one patient showed typical sensory aphasia as the
      first symptom, and another patient showed nonverbal auditory agnosia followed by
      pure word deafness. Thus, patients with Landau-Kleffner syndrome show sequential
      and sometimes hierarchical language disorders beginning with sensory aphasia,
      followed by auditory agnosia, and finally word deafness during their disease
      process. During long-term follow-up (20 to 30 years), all patients showed marked
      recovery in language without any intellectual handicap, but with some disability
      in spoken language, auditory verbal perception, and a discrepancy between
      Wechsler Verbal and Performance IQ scores.

PMID- 10073435
TI  - Clinical, pathologic, and neurochemical studies of an unusual case of neuronal
      storage disease with lamellar cytoplasmic inclusions: a new genetic disorder?
AB  - A child of first-cousin Puerto Rican parents had global developmental delay,
      failure to thrive, and hypotonia since early infancy. At 1 1/2 years of age, she
      developed clinical and electrophysiologic evidence of progressive motor and
      sensory neuropathy. At 2 1/2 years, she developed visual impairment and optic
      atrophy followed by gradual involvement of the 7th, 9th, 10th, and 12th cranial
      nerves. Uncontrollable myoclonic seizures began at 4 years and she died at 6
      years of age. Motor nerve conduction velocities were initially normal and later
      became markedly slowed. Sensory distal latency responses were absent. Lysosomal
      enzyme activities in leukocytes and fibroblasts were normal. Sural nerve and two
      muscle biopsies showed only nondiagnostic abnormalities. Electron microscopy of
      lymphocytes, skin, and fibroblasts showed cytoplasmic inclusions. Light
      microscopy of frontal cortex biopsy showed neuronal storage material staining
      positively with Luxol fast blue, and electron microscopy showed cytoplasmic
      membranous bodies in neurons, suggesting an accumulation of a ganglioside. At
      autopsy, all organs were small but otherwise normal and without abnormal storage
      cells in the liver, spleen, or bone marrow. Anterior spinal nerve roots showed
      loss of large myelinated axons. The brain was small and atrophic; cortical
      neurons showed widespread accumulation of storage material, most marked in the
      pyramidal cell layer of the hippocampus. Subcortical white matter was gliotic
      with loss of axons and myelin sheaths. In cortical gray matter there was a 35%
      elevation of total gangliosides, with a 16-fold increase in GM3, a three- to four
      fold increase in GM2 gangliosides, and a 15-fold elevation of lactosyl ceramide.
      GM3 sialidase activity was normal in gray matter at 3.1 nmols/mg protein per hour
      and lactosyl ceraminidase I and II activities were 70% to 80% of normal. In white
      matter, total myelin was reduced by 50% but its composition was normal.
      Phospholipid distribution and sphingomyelin content were normal in gray matter,
      white matter, and in the liver. These biochemical findings were interpreted as
      nonspecific abnormalities. The nature of the neuronal storage substance remains
      to be determined.

PMID- 10073436
TI  - Phenytoin-associated thrombocytopenia in a toddler.
AB  - Hematologic side effects are rare side effects of treatment with phenytoin. We
      report a 2-year-old girl who developed reversible thrombocytopenia following
      treatment with phenytoin. Thrombocytopenia as a side effect of phenytoin
      treatment has usually been reported in adults and generally occurs 2 to 4 weeks
      after initiation of therapy. In our case, the thrombocytopenia developed on the
      11th day of therapy and resolved 5 days after discontinuation of the phenytoin.

PMID- 10073437
TI  - Congenital hydranencephalic-hydrocephalic syndrome associated with mitochondrial
      dysfunction.
AB  - We report the case of a 3-year-old girl, the only child of a nonconsanguineous
      couple without relevant antecedents, who was born with hydranencephalic
      hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who
      was treated during the neonatal period by implantation of a ventriculoperitoneal
      shunt. She showed severe mental retardation, and died at age 4 years following an
      acute respiratory infection. Due to persistently high lactic acid levels in
      blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed
      microscopic and ultrastructural alterations typical of mitochondrial disorders,
      and low levels of complexes III and IV of the mitochondrial respiratory chain.
      The enzymes of the pyruvate dehydrogenase complex showed normal activities in
      cultured skin fibroblasts. These findings raise the possibility that at least
      some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to
      alterations in the mitochondrial respiratory chain.

PMID- 10073438
TI  - Patch test reactions at D4, D5 and D6.
AB  - In this retrospective study, patch test reactions in 3 groups of patients were
      analysed, in order to obtain information on the best day for the 2nd patch-test
      reading after day 2 (D2), on the usefulness of additional readings after D3, and
      on the dependence of patch-test reactions at D4, D5, or D6 on allergen and/or
      patient characteristics. In the years 1990 to 1995, patch tests were routinely
      read at D3 and D4 in 1096 patients, at D3 and D5 in 1243 patients, and at D3 and
      D6 in 1136 patients. In all of the 3 groups, significantly more positive
      reactions diminished than appeared de novo from D3 to the later reading.
      Virtually identical results were observed in subgroups of patients formed by sex,
      age or atopy. However, men might possibly react more slowly than women on patch
      testing, showing more increasing than diminishing reactions in the D3/D4- and the
      D3/D5-comparison. Reactions to individual allergens showed wide differences in
      this connection. Neomycin sulfate, cobalt salts, and p-phenylenediamine can be
      characterized as slow allergens, with more reactions increasing than diminishing
      from D3 to the later readings. With fragrance mix and balsam of Peru, the
      opposite pattern occurred. In all subgroups of patients, and with most allergens,
      the gain in positive reactions was biggest when an additional reading was
      performed at D5. We conclude that for a single 2nd patch test reading after D2,
      D3 is the best day, and especially better than D4. If a 3rd reading is performed,
      it should be done at D5 to get the maximum information out of patch testing.
      However, this extends the test procedure to at least 1 day of the weekend.

PMID- 10073439
TI  - Are contact allergens stable in patch test preparations? Investigation of the
      degradation of d-limonene hydroperoxides in petrolatum.
AB  - Several of the products formed after oxidation of d-limonene exhibit strong
      contact allergenic properties. Some, e.g., the hydroperoxides, are unstable
      compounds. In this study, we have examined whether the limonene hydroperoxides
      are chemically stable in white petrolatum used for patch testing. We found that
      the stability of the hydroperoxides was strongly dependent on whether or not the
      petrolatum was stabilized with alpha-tocopheryl acetate. In the presence of this
      antioxidant, the hydroperoxides were degraded to a greater extent. The
      hydroperoxides were shown to be directly reduced to the corresponding alcohols by
      this agent. On the other hand, the compounds where shown to be stable in non
      stabilized petrolatum throughout clinical patch testing for a period of 6 weeks,
      provided that the preparations were stored in a refrigerator when not used. Thus,
      it is recommended that vehicles without alpha-tocopheryl acetate are used when
      peroxy or hydroperoxy compounds are patch tested or used in sensitization
      experiments. However, it is important to limit the storage time so that optimal
      conditions are at hand. A fast method was developed to enable isolation and
      quantification of the hydroperoxides in white petrolatum. This analytical method
      may also be applicable to other compositions of patch test preparations.

PMID- 10073440
TI  - A hand immersion test under laboratory-controlled usage conditions: the need for
      sensitive and controlled assessment methods.
AB  - Exaggerated test conditions were frequently used to investigate the cutaneous
      tolerance of detergent products in the past. As the sensitivity of newly designed
      biometric methods is steadily improving, the trend towards more realistic test
      conditions should be encouraged. A hand immersion test under laboratory
      controlled usage conditions is presently described, fulfilling such principles.
      Panelists soaked their hands in 2 different hand dishwashing liquids, 2x daily
      for 10 min each (with successive in-solution/out-of-solution cycles) for 4
      consecutive days. Products were at usual dilution for dishwashing liquids and
      were randomized between the dominant and non-dominant hands of panelists. Visual
      scoring of erythema and dryness developing on the whole hands (scoring scales
      including interdigital areas and joints) during the week did not allow
      discrimination between the 2 products. However the dominant hands were
      significantly more susceptible to alterations than the non-dominant hands,
      regardless of product attribution. In contrast, skin electrical measurements
      (Corneometer CM800 and Skicon 200) on the dorsum of the hands (muscle mass
      between thumb and index) and squamometry analysis of tape stripping (harvested
      from the same site) yielded significant differences between the 2 products. In
      conclusion, a hand immersion test under realistic conditions has been described,
      which discriminates between products when sensitive assessment methods are used
      to explore skin sites partially protected from daily-life skin aggressions.

PMID- 10073441
TI  - Sensitizing potential of acetaldehyde and formaldehyde using a modified
      cumulative contact enhancement test (CCET).
AB  - The contact allergenic activity of acetaldehyde was investigated with a modified
      cumulative contact enhancement test (CCET) method in guinea pigs. Possible cross
      reactivity between acetaldehyde and formaldehyde was also studied. In contrast to
      the original CCET protocol, we used sham-treated controls and the chemicals were
      tested with closed epicutaneous application at 1st challenge. The suitability of
      the method was verified with formaldehyde and the results were comparable with
      those previously found with the guinea pig maximization test (GPMT). For the 1st
      time, acetaldehyde was shown to be a contact allergen in predictive tests. No
      cross-reactivity was observed between acetaldehyde and formaldehyde. Acetaldehyde
      seems to be a rare sensitizer in man. However, its allergenic activity should be
      considered, since it might be present as an impurity in ethoxylated surfactants.
      As the CCET protocol involves topical induction and challenge, we regard the
      modified version as well suited to evaluation of the contact allergenic potential
      of chemicals.

PMID- 10073442
TI  - Does sodium lauryl sulfate concentration vary with time?
AB  - When performing skin irritation tests with sodium lauryl sulfate (SLS), the
      quality of the test solution is of major importance for the reproducibility and
      comparability of the results. The influence of 4 different storage parameters
      (concentration, duration, temperature, material of the storage vials) on the
      stability of aqueous SLS solutions was investigated under non-sterile conditions.
      SLS solutions at 5 different concentrations (0.001%, 0.01%, 0.1%, 0.5%, 1%) were
      analysed by mobile phase ion chromatography. Analyses were performed after a
      storage time of 3 h, 1 week, and 4 weeks. Storage was carried out at different
      temperatures: -18 degrees C, 6 degrees C, and 23 degrees C. The storage
      containers were of 2 different materials (glass and polypropylene). After a
      storage of 1 week, no decrease in SLS concentration was observed, regardless of
      the chosen conditions. After 4 weeks at 6 degrees C and 23 degrees C, the SLS
      concentration was found to be significantly decreased for the 2 lowest
      concentrations (0.001% and 0.01%). At higher concentrations and lower
      temperatures, no decrease in SLS concentration had occurred. In parallel to the
      loss of SLS, contamination with bacteria was found in the solutions, especially
      at the 2 lowest concentrations. Bacterial growth was not observed at higher
      concentrations. The possibility of biodegradation of SLS has to be taken into
      account, especially when dealing with low concentrations of SLS.

PMID- 10073443
TI  - Skin sensitization risk assessment: a comparative evaluation of 3 isothiazolinone
      biocides.
AB  - Many of the chemicals in common use possess, to some degree, a capacity to cause
      skin sensitization. Consequently, it is important to conduct a thorough and
      accurate risk assessment when it can be anticipated that such chemicals are
      likely to come into contact with human skin. Such risk assessments must consider
      the nature and extent of dermal exposure together with the sensitizing potency of
      the chemical. Whilst the exposure elements of the risk assessment process are
      often well understood, or can at least be reasonably predicted on the basis of
      the proposed usage of the chemical, the determination of skin sensitizing potency
      may be problematic. In this paper, we describe an approach to the determination
      of relative potency of 3 isothiazolinone biocides. Initially, the local lymph
      node assay (LLNA) provides an estimate of relative sensitizing potency. Where
      appropriate, this can be followed by confirmatory testing in the human repeat
      insult patch test (HRIPT). The data generated reveal that (chloro)methyl
      isothiazolinone (CMI) is a significantly stronger sensitizer than either methyl
      trimethylene isothiazolinone (MTI) or benzisothiazolinone (BIT). Furthermore,
      both the LLNA and the HRIPT data show consistently that BIT is a somewhat weaker
      skin sensitizer than MTI. As an important additional component of the safety
      evaluation, the ability of these sensitizing isothiazolinones to cross-react has
      been considered; the data indicate that the more weakly sensitizing
      isothiazolinones do not elicit allergic reactions in subjects sensitized to MCI.
      The implications for use of these biocides in various product types are
      discussed.

PMID- 10073444
TI  - Screening patch tests for pigmented contact dermatitis in Israel.
AB  - Pigmented contact dermatitis has been found to be caused by fragrances,
      cosmetics, washing powders, azo dyes in textiles, and rubber products in selected
      groups of patients. The aim of this study was to run screening patch tests in an
      unselected group of patients with pigmented contact dermatitis (n=29) encountered
      in our center over a 2-year period. The test series included the European
      standard, cosmetics, fragrance, Scandinavian photo, and personal products. 21
      patients had a positive reaction in at least 1 of the series (total, 29
      reactions): 16 - standard, 3 - cosmetics, 1 fragrance, 9 photo, and 1 - personal
      products; 16 (55%) had relevant results. We conclude that the highest yield for
      screening for pigmented contact dermatitis is achieved with the standard and
      photo series.

PMID- 10073445
TI  - Eczematous reaction to hepatitis B vaccine.

PMID- 10073446
TI  - Contact dermatitis due to urea-formaldehyde resin in shin-pads.

PMID- 10073447
TI  - Eczematous erythroderma induced by cyanamide.

PMID- 10073448
TI  - Value of patch tests in pristinamycin-induced drug eruptions.

PMID- 10073449
TI  - Contact dermatitis caused by benzoyl peroxide in podiatrists.

PMID- 10073450
TI  - Allergic contact dermatitis from sodium metabisulfite in Trimovate cream.

PMID- 10073451
TI  - Occupational allergic contact dermatitis from cassia (Chinese cinnamon) as a
      flavouring agent in coffee.

PMID- 10073452
TI  - The recognition of occupational allergic contact dermatitis in Warsaw.

PMID- 10073453
TI  - Occupational dermatoses among laboratory assistants.

PMID- 10073454
TI  - Benign familial chronic pemphigus (Hailey-Hailey) provoked by contact sensitivity
      in 2 patients.

PMID- 10073455
TI  - Octopus apollyon bite.

PMID- 10073456
TI  - Baboon syndrome from i.v. aminophylline in a patient allergic to ethylenediamine.

PMID- 10073457
TI  - PVP/hexadecene copolymer: a hard-to-find allergen in modern times.

PMID- 10073458
TI  - Effects of sex and laterality on the rotatory swimming behavior of normal mice.
AB  - Clockwise and counterclockwise full turns are commonly used to assess
      lateralization in circling behavior. Although previous studies have reported that
      the rotatory swimming (ROSW) test is simple and reliable, little is known about
      lateralization of turns lower than 360 degrees and the amount of turning close to
      the wall, and even less is known about alternation of direction during a session.
      Here we investigated the effects of consistency of laterality and sex on 30
      degree turns in center and in periphery of the swimming apparatus, and on
      alternation of direction upon three sessions. Approximately 80% of the turns
      occurred when mice swam along the wall. In side-consistent turners, this suggests
      the existence of an intrinsic sensorimotor asymmetry that determines the adhesion
      to the preferred side. Regarding categorization of side preferences, there was a
      high percentage of agreement between center and periphery, as well as between
      full turns and extra 30 degree turns (30 degree turns that do not contribute to
      full turns). Therefore, behavioral asymmetry in the ROSW can be assessed using 30
      degree turns. There was no significant directional bias in the population, and
      side preference was found to be independent of sex. By contrast, after the second
      minute of each session, males exhibited a significantly higher number of reversal
      of direction (RD) as well as a higher number of RD per turn than females. The
      amount of RD presented by each animal is not predicted by the animal's side
      preference. Thus, RD is independent of preferred side of turning and depends on
      sex.

PMID- 10073459
TI  - Temporary amnesia induced by cold anesthesia and hypoxia in Drosophila.
AB  - Memory consolidation in Drosophila was investigated using cold anesthesia- and
      hypoxia-induced amnesia. Individual flies were operantly trained to avoid the
      specific flight orientations with respect to the landmarks surrounding them when
      paired with heat reinforcement at a flight simulator. Cold anesthesia, introduced
      immediately after training, exerted a significantly diminishing effect on memory
      between 15 and 150 min after training. Hypoxia delivered immediately after
      training had a significantly diminishing effect on memory between 30 and 150 min
      after training. In addition, cold anesthesia disrupted memory only when
      introduced within the first 20 min, while hypoxia worked only when delivered
      within the first 2 min after training. When interpreted in the context of a four
      phase model of memory consolidation, the results suggest that 1) cold anesthesia
      disrupts both short-term memory (STM) and anesthesia-resistant memory (ARM), 2)
      hypoxia disrupts ARM specifically, 3) both of them leave long-term memory (LTM)
      intact, and 4) LTM may be independent of availability of STM and ARM in flies.

PMID- 10073460
TI  - Meal-engendered circadian-ensuing activity in rats.
AB  - Large meals scheduled at greater-than-circadian periods (such as T = 31 h) tend
      to elicit enhanced activity approximately 24 h subsequent to receipt. These
      studies characterized the process responsible for this meal-engendered "circadian
      ensuing activity" (meal CEA). Female Sprague-Dawley rats were housed in stations
      containing a running wheel, pellet dispenser, and lights. Young, middle-aged, or
      suprachiasmatic-nucleus (SCN)-lesioned rats were given two 1-h meals every 31 or
      34 h. Meals were separated by alternating short and long fasts. Most young intact
      rats engaged in enhanced activity approximately 24 h subsequent to the start of
      the two-meal series. This circadian ensuing activity underwent large, abrupt
      daily displacements in response to daily meal delays, was manifested to some
      degree at all times of day, had an amplitude that was modulated by circadian time
      of day, was attenuated in middle-aged rats, was evident in SCN-lesioned rats, and
      oscillated following termination of the feeding schedule. A single experience
      with food at a novel time of day can "reset" an SCN-independent oscillating
      process responsible for a circadian activity pattern. CEA has features not
      readily accommodated by present models of "food-anticipatory activity." The
      readiness with which the process can be reset implies a keen sensitivity to
      shifts in the time of food availability but could also produce aberrant
      behavioral patterns. A T >> 24-h feeding schedule appears to be an ideal
      procedure with which to study the specific food-related factors responsible for
      resetting circadian processes and producing a subsequent reallocation of daily
      activity.

PMID- 10073461
TI  - An examination of the effects of isoenergetic intragastric infusions of pure
      macronutrients on cold pain perception in healthy human volunteers.
AB  - Our previous study demonstrated that meals, particularly when rich in fat,
      significantly reduced the pain induced by the cold pressor stimulus in healthy
      human subjects. To determine the mechanisms involved, the aim of this study was
      to bypass the taste and cognitive component of food and to investigate the scope
      of these analgesic effects with direct intragastric infusion of pure
      macronutrients in a group of 16 healthy human volunteers (eight male and eight
      female) on the response to cold-induced pain. All subjects underwent the cold
      pressor test (CPT) on three occasions in a counterbalanced order: before and
      after intragastric intubation and infusion of isoenergetic fat (10% intralipid),
      carbohydrate (CHO-maltodextrin), and a control infusion of isotonic saline. All
      solutions were of equal volume and administered at room temperature. The CPT was
      carried out four times on each test day, once before intubation, and 0.5, 1.5,
      and 2.5 h after intragastric infusion. Radial pulse and blood pressure
      measurements and visual analogue scales of mood/emotional state were carried out
      before and after each CPT. There were no significant differences in pain scores
      between the three test conditions, suggesting that by bypassing the cognitive and
      taste component of eating, the trigger for any postingestive analgesic effects of
      food are lost.

PMID- 10073462
TI  - Heart rate variability during manual restraint in chicks from high- and low
      feather pecking lines of laying hens.
AB  - The purpose of this investigation was to determine whether there is a difference
      in coping style in chicks from a high (HFP)- and low-feather pecking (HFP) line
      of laying hens. Active and passive coping styles can be distinguished by
      differences in sympathetic and parasympathetic activities on the heart. We
      studied heart rate during baseline conditions and during manual restraint in HFP
      and LFP hens. Heart rate and locomotor activity were successfully monitored
      around the clock with a biotelemetric implant. During the light period, the
      values for locomotor activity and heart rate were highest, whereas during the
      dark period they were the lowest. These values did not differ in LFP and HFP
      hens. However, during manual restraint (restraining the bird on its side by hand
      for 8 min) HFP birds had somewhat faster heart rate than LFP birds (at 4 min, p =
      0.066). Studying heart rate variability during manual restraint showed that LFP
      chickens had a significant higher parasympathetic activity at 5 min (p = 0.023)
      and at 6 min (p = 0.002) as compared to HFP hens. The results showed that in
      terms of coping style, LFP chickens are passive, whereas HFP birds are active.

PMID- 10073463
TI  - Determination, using microdialysis, of hypothalamic serotonin variations in
      response to different macronutrients.
AB  - In response to a chow meal in rats, we observed previously in PVN-VMH dialysates,
      an increase in serotonin (5-HT) that could be related to satiety or to metabolic
      consequences of the composition of the meal. Indeed, carbohydrates are admitted
      to increase 5-HT synthesis while proteins decrease it, but the time course and
      mechanisms of these effects were not known. For that purpose, pure carbohydrates,
      proteins, or fats were offered for 30 min and the changes in 5-HT from PVN-VMH
      dialysates were followed. Carbohydrates (85% starch + 15% sucrose) enhanced 5-HT
      levels as soon as the first 15 min of feeding, with a maximum 60 min later.
      Conversely, protein ingestion induced in the second 15 min of the meal, a
      decrease in 5-HT that lasted 2 h. During a fat meal (lard), 5-HT levels also
      decreased at the beginning of the meal and remained low during 45 min. The
      present data reassess the previous theories on the serotonergic effects of
      specific macronutrient ingestion. The effect of a fat meal on 5-HT levels had
      never been described so far. The increase in 5-HT in response to a carbohydrate
      meal is further specified. The 5-HT decrease induced by proteins, in agreement
      with the previous theories, is better explained now by using pure protein diets
      and extracellular 5-HT assay. However, all the changes observed start too early
      to be only metabolic in origin. Other mechanisms may occur, including the release
      of 5-HT in response to a meal to induce satiety.

PMID- 10073464
TI  - Actigraphic assessment of sleep in insomnia: application of the Actigraph Data
      Analysis Software (ADAS).
AB  - The usefulness of the actigraph methodology has been demonstrated in normal
      individuals. However, the validity of actigraphy has been questioned in insomnia
      patients because of the considerable measurement error that has been reported
      between actigraphy (ACT) and polysomnography (PSG). Two independent
      investigations have reported errors of 48 and 49 min in total sleep time between
      ACT and PSG. With a new scoring method called the Actigraph Data Analysis
      Software, a reanalysis of one of these studies was conducted. Based on this
      reanalysis, we have obtained a measurement error of only 25 min between the two
      methods. This finding may be an indication of the advantage of this new scoring
      method. A strong correlation coefficient (r = 0.82, p < 0.0001) was noted between
      ACT and PSG for total sleep time, thus suggesting a high degree of accuracy of
      the actigraph methodology in assessing the sleep/wake profile of insomniacs.

PMID- 10073465
TI  - Lowered sperm motility in subordinate social status of mice.
AB  - The correlation between social status and sperm motility of mice was
      investigated. From 5 to 15 weeks of age, mice were kept under two housing
      conditions, i.e., in pairs or in isolation. The social dominance in the paired
      mice was determined with the resident-intruder tests, which were carried out from
      8 to 15 weeks of age. At the end of 15 weeks of age, sperm activity, weights of
      reproductive organs, and serum testosterone were determined. It was revealed that
      the sperm motility of dominant mice was significantly higher than that of the
      subordinates. The sperm motility of the isolated mice was also significantly
      higher than the subordinates. It was suggested that the subordinate social status
      lowered sperm motility.

PMID- 10073466
TI  - Effects of food restriction on glucose tolerance, insulin secretion, and islet
      cell proliferation in pregnant rats.
AB  - Pregnancy is associated with increased glucose-stimulated insulin secretion and
      increased pancreatic islet-cell proliferation. In the present study it was
      investigated whether increased food intake, as occurs during pregnancy, is
      involved in the regulation of these phenomena. From Day 0 of pregnancy, rats
      received each day the mean amount of food they consumed daily during the estrous
      cycle prior to conception. This food restriction regime resulted in lower
      maternal body weight, and in lower fetal weight on Day 20 of gestation, but did
      not affect fetal survival. Food-restricted rats showed decreased insulin
      responses to an i.v. glucose challenge on Day 13, and lower islet-cell
      replication rates on Day 14 of pregnancy than pregnant rats fed ad lib. Plasma
      lactogenic activity in food-restricted animals was increased on Days 11 and 13;
      plasma progesterone levels were unchanged, but plasma leptin concentrations
      declined progressively during food restriction. Glucose tolerance was normal,
      suggesting that food restriction improved insulin action. On Day 20 of pregnancy,
      insulin responses were similar in food restricted and ad lib-fed rats; glucose
      tolerance was still unchanged. It thus seems that the improved insulin action as
      present on Day 13 had disappeared on Day 20. Also on Day 20, lactogenic activity
      as well as progesterone concentrations were similar in food-restricted and ad lib
      fed rats. It was concluded that increased food intake plays an important role in
      the stimulation of islet-cell proliferation and insulin secretion, as well as in
      the diminished insulin action during the second week of rat pregnancy.

PMID- 10073467
TI  - Psychoneurogastroenterology: interrelations in stress-induced colonic motility
      and behavior.
AB  - Individual differences in behavioral and physiological response patterns to
      stress may contribute to vulnerability for stress-related illnesses such as
      functional gastrointestinal disorders. Animal models could give clues about
      specific individual determinants of intestinal reactivity to stress and stress
      induced sensitization. Rats fitted with permanent electrodes on the proximal
      colon were exposed to a single session of foot shocks (10 x 6 s in 15 min,
      preshocked) or no shocks (control). Two weeks later, the preshocked group showed
      a significantly greater colonic spike burst response to a novel shock-prod
      stressor in the home cage than controls. The increase in burst frequency was
      positively correlated with the duration of active burying of the threatening prod
      in both experimental groups, but not with other behavioral components. Basal
      colonic burst frequency at rest was negatively correlated with the increase in
      burst frequency due to shock-prod stress in both groups, but the degree of
      sensitization in preshocked rats vs. controls was of similar magnitude in rats
      with low and high basal colonic burst frequency. The results indicate that
      colonic responsivity to stress is related to both basal motility status and
      individual coping strategies.

PMID- 10073468
TI  - The effects of NPY and 5-TG on responding to cues for fats and carbohydrates.
AB  - Previous research has shown that glucoprivic and lipoprivic metabolic challenges
      selectively augment the performance of appetitive responses conditioned to
      carbohydrate- and fat-associated cues, respectively. The present experiment
      investigated whether intracerebroventricular (i.c.v.) infusion of neuropeptide Y
      (NPY) has a similar selective effect on appetitive behavior. We trained rats to
      associate two different conditioned stimuli (CSs) with two different
      macronutrient (peanut oil and sucrose pellets) unconditioned stimuli (USs). After
      training, the rats were food sated and responding to each CS was then tested in
      extinction. In one test session, the effects of NPY were compared to isotonic
      saline. A second test compared the effects of these two treatments with i.c.v.
      infusion of the glucose antimetabolite 5-thio-d-glucose (5-TG). Replicating our
      earlier result, 5-TG selectively promoted conditioned responding to the CS for
      sucrose pellets. In contrast, the capacity of NPY to promote appetitive behavior
      did not depend on the macronutrient that was signaled by the CS. These results
      suggest that NPY and 5-TG promote appetitive behavior via different mechanisms.

PMID- 10073469
TI  - Influence of social status on ovarian function in farmed red deer (Cervus
      elaphus).
AB  - This study examines the effects of behavioural and environmental factors on
      ovarian function in red deer hinds. Patterns of postovulatory luteal progesterone
      secretion were investigated in groups of farmed red deer hinds following oestrus
      induced by progesterone administration and withdrawal. Hinds were held under
      conditions leading to low (Experiment 1, held in paddocks: 0.29 per animal/h) or
      high (Experiment 2, held in pens: 1.11 per animal/h) interaction rates, and
      progesterone was measured in jugular venous blood samples obtained daily for 14
      days after ovulation. Plasma progesterone levels tended to differ with respect to
      dominance status in both experiments (p < 0.1). Progesterone levels were
      substantially lower following prolonged hot dry weather (mean 0.67 +/- SEM 0.03
      ng/mL) than in a year of relatively typical climatic conditions (mean 1.63 +/-
      0.04 ng/mL; p < 0.0005). Progesterone levels were not related to the body weight
      of the hinds, and were not affected by housing conditions leading to different
      interaction rates. We conclude that although there is a tendency for dominance
      status to affect ovarian function, as observed before, this relationship is
      obscured in farmed red deer where all animals in the herd enjoy a higher plane of
      nutrition and movements of individuals between groups confuse dominance
      relationships.

PMID- 10073470
TI  - The effects of restraint stress on intake of preferred and nonpreferred solutions
      in rodents.
AB  - In these experiments we determined whether stress influenced intake of different
      flavored test solutions or only those that were preferred. In a series of
      studies, rats or hamsters were exposed to acute (1 h) or repeated (3 h/day for 3
      days) restraint stress immediately followed by access to one of four tastants
      (saccharin, salt, citric acid, or quinine solutions) paired with water in a 24-h
      preference test. As rats prefer salt and hamsters do not, both species were used
      to test the effects of stress on preferred vs. nonpreferred solutions using the
      same stimulus. Acute restraint inhibited intake of saccharin in rats but had no
      effect on preference, indicating that suppression of intake was not due to
      changes in hedonic response. Restraint had no effect on saccharin intake of
      hamsters but significantly increased salt intake. However, as the preference
      ratio remained low for the solution (0.26), the stress-induced increase in salt
      intake was probably associated with a disturbance of sodium and fluid balance
      rather than a change in sensory perception. This was supported by stress having
      no effect on intake of nonpreferred solutions in rats or hamsters. Repeated
      restraint had no effect on salt or saccharin intake of rats when test solutions
      were presented after stress, but rats showed no preference for saccharin in a
      subsequent study in which the solution was associated with onset of stress. These
      results indicate that stress has specific effects on saccharin and salt intake
      that are not limited to preferred solutions.

PMID- 10073471
TI  - Protein meals and postprandial thermogenesis.
AB  - In North America the consumption of meat far exceeds that of fish. Because the
      palatability of the food has been shown to influence the thermogenic response to
      feeding, a study was designed to compare the metabolic response to 195-g beef
      steak and 250-g cod fillet containing both 43 g of proteins in a first experiment
      and to 250 g of both nutrients in a second experiment. The subjects who
      participated in this study gave a higher rating of palatability (obtained on a 10
      cm visual analog scale) when the beef steak (7.4) was consumed compared to the
      cod fillet (3.0). Measurements of oxygen consumption during the cephalic phase (0
      to 40 min) indicated a larger thermogenic response to the beef than to the fish
      meal. These findings suggest that the thermic response to feeding during the
      cephalic phase are related to the sensory stimulation of the meal. During the
      gastrointestinal phase (40 to >180 min) the response was not influenced by the
      type of food and was related instead to the amount of proteins ingested. Plasma
      amino acid determinations indicated differences between the beef and fish
      feeding. Plasma histidine and glutamine was higher after beef feeding. The
      meaning of these findings does not seem to be related at this time to the results
      obtained on postprandial thermogenesis. The increases in plasma insulin that were
      observed during both phases of feeding were similar for the beef and the fish
      meals. Despite a marked increase of insulin, plasma glucose remained unchanged
      after feeding either meals, suggesting an enhanced gluconeogenesis and an
      increased glucose utilization.

PMID- 10073472
TI  - The contribution of changes in milk delivery to the prolongation of lactational
      infertility induced by food restriction or increased litter size.
AB  - In rats, the length of lactational anovulation is prolonged when litter size is
      increased or when the dam is food restricted. In both of these situations the
      energetic demand on the dam is increased, milk delivery to each pup is reduced,
      and consequently, patterns of pup suckling may be changed. We investigated the
      contribution of these factors to the maintenance of lactational anovulation by
      examining the effect of eliminating milk delivery on the length of lactational
      diestrus in food restricted and ad lib-fed females nursing litters of 8 pups and
      in females nursing large (14 pups) and small (6 pups) litters. The results of
      these studies show that preventing milk delivery neither extends the period of
      lactational infertility in ad lib-fed females nursing eight pups nor eliminates
      the effects of increasing litter size on this period.

PMID- 10073473
TI  - Intra- and extracellular dehydration-induced thirst-related behavior in an
      amphibian.
AB  - The behavioral response to dehydration is critical to an animal's survival.
      Because of their permeable skin, amphibians are particularly sensitive to
      dehydrating conditions. We tested the hypothesis that different forms of
      dehydration induce water absorption response (WR) behavior in the desert
      spadefoot toad, Scaphiopus couchii. First, we determined the behavioral response
      to intracellular dehydration by treating fully hydrated toads with increasing
      concentrations of hypertonic solutions of NaCl or sucrose via intraperitoneal
      injection (i.p.). Animals that were treated to induce intracellular dehydration
      with either solute exhibited a significant increase in WR behavior compared to
      vehicle-treated controls. To distinguish that the response was a result of an
      increased osmotic gradient between the intra- and extracellular compartments, we
      treated fully hydrated animals i.p. with urea, which freely passes into the
      intracellular compartment and increases overall animal osmolarity. Urea treatment
      did not induce WR behavior. To determine the response to extracellular
      dehydration, the blood volume of fully hydrated toads was reduced via cardiac
      puncture, and the WR behavior was measured. Animals who had a reduction in blood
      volume exhibited a significant increase in WR behavior compared to sham-punctured
      controls. Our results are the first to demonstrate that multiple forms of
      dehydration can induce thirst-related behavior in amphibians.

PMID- 10073474
TI  - NMDA receptors mediate lasting increases in anxiety-like behavior produced by the
      stress of predator exposure--implications for anxiety associated with
      posttraumatic stress disorder.
AB  - It has been proposed that NMDA-dependent long-term potentiation (LTP) of limbic
      system circuits controlling defensive behavior underlies stressor-induced lasting
      increases in anxiety-like behavior (ALB). Findings in cats given the stress
      inducing beta-carboline, FG-7142, support this hypothesis. An animal model of
      lasting affective change following traumatic stress has recently been developed.
      In this model, lasting increases in anxiety-like behavior (ALB) assessed in the
      elevated plus maze are produced by a single 5-min exposure of a rat to a cat.
      Rats become more anxious in the plus maze for up to 3 weeks after the exposure.
      The present study demonstrates that blockade of NMDA receptors in rats with MK
      801, AP7, or CPP, given 30 min prior to exposure to a cat, prevents the increase
      in ALB assessed 1 week later. MK-801 or AP7, given 30 min after exposure to a
      cat, do not prevent the increase in ALB seen 1 week later, however. MK-801, but
      not CPP or AP7, promotes approaches to cats during exposure. This "fearlessness"
      may reflect some anxiolytic action of MK-801. Approach to cats following
      injection of MK-801 was eliminated by prior injection of Prazosin. Prazosin did
      not interfere with the block of increases in ALB following cat exposure, however.
      These findings are consistent with the view that NMDA receptors are involved in
      initiation, but not maintenance of neural changes mediating lasting increases in
      anxiety following severe stress. The significance of these findings for PTSD are
      discussed.

PMID- 10073475
TI  - Unilateral block of NMDA receptors in the amygdala prevents predator stress
      induced lasting increases in anxiety-like behavior and unconditioned startle-
      effective hemisphere depends on the behavior.
AB  - Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are
      produced by a single 5-min exposure of a rat to a cat. Rats become more anxious
      in the plus-maze for up to 3 weeks after the exposure. The first study in this
      series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or
      CPP, given systemically 30 min prior to exposure to a cat prevents the increase
      in ALB assessed 1 week later in the elevated plus-maze. To localize the site of
      action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to
      predator stress. Injections were given either unilaterally in either hemisphere,
      or bilaterally in both hemispheres. The target of the injection was the
      basolateral amygdala. The effects of injection depended on both the type of
      behavior and the hemisphere of injection. Injections of MK-801 in a variety of
      sites in the basolateral amygdala had no effect on the suppression of open-arm
      exploration produced by predator stress. Other amygdala nuclei or other limbic
      sites likely mediate the effects of systemically administered MK-801 on this
      behavior. In contrast, NMDA receptors in the left lateral amygdala mediate
      lasting suppression of risk assessment. MK-801, in a variety of sites in the left
      but not right lateral amygdala, blocked the effects of predator stress on risk
      assessment. This is clear evidence of separability of neural mechanisms
      controlling open-arm exploration and risk assessment. Different NMDA-dependent
      amygdala circuitry mediated effects of predator stress on unconditioned acoustic
      startle 1 week after cat exposure. The data indicate that integrity of the left
      lateral amygdala is necessary for potentiation of startle amplitude by predator
      stress, though NMDA receptors are not involved in this function. Nevertheless,
      NMDA receptors in the right, but not the left lateral amygdala, mediate
      initiation of changes in startle. The data also suggest that the right amygdala
      action is "downstream" from the left amygdala contribution. These findings are
      consistent with the view that NMDA receptors are involved in initiation, but not
      maintenance, of neural changes mediating lasting increases in anxiety following
      severe stress. Finally, the findings of the importance of the right amygdala in
      stress-induced enhancement of the startle response provides neurobiological face
      validity to predator stress as a model of aspects of posttraumatic stress
      disorder.

PMID- 10073476
TI  - Ultrawide-band electromagnetic pulses induced hypotension in rats.
AB  - The ultrawide-band (UWB) electromagnetic pulses are used as a new modality in
      radar technology. Biological effects of extremely high peak E-field, fast rise
      time, ultrashort pulse width, and ultrawide band have not been investigated
      heretofore due to the lack of animal exposure facilities. A new biological
      effects database is needed to establish personnel protection guidelines for these
      new type of radiofrequency radiation. Functional indices of the cardiovascular
      system (heart rate, systolic, mean, and diastolic pressures) were selected to
      represent biological end points that may be susceptible to the UWB radiation. A
      noninvasive tail-cuff photoelectric sensor sphygmomanometer was used. Male Wistar
      Kyoto rats were subjected to sham exposure, 0.5-kHz (93 kV/m, 180 ps rise time,
      1.00 ns pulse width, whole-body averaged specific absorption rate, SAR = 70
      mW/kg) or a 1-kHz (85 kV/m, 200 ps rise time, 1.03 ns pulse width, SAR = 121
      mW/kg) UWB fields in a tapered parallel plate GTEM cell for 6 min. Cardiovascular
      functions were evaluated from 45 min to 4 weeks after exposures. Significant
      decrease in arterial blood pressures (hypotension) was found. In contrast, heart
      rate was not altered by these exposures. The UWB radiation-induced hypotension
      was a robust, consistent, and persistent effect.

PMID- 10073477
TI  - Effects of cold exposure on estrous behavior and neural estrogen receptor in
      Syrian hamsters.
AB  - Two experiments examined the effects of 72-h exposure to reduced environmental
      temperature (5 degrees C) on steroid-induced estrous behavior and neural estrogen
      receptor immunoreactivity (ERIR) in ovariectomized Syrian hamsters. Cold exposure
      significantly inhibited sexual receptivity induced by sequential injections of
      estradiol benzoate (2.5 microg) and progesterone (500 microg), but only if the
      animals were not permitted to overeat (limited to 110% of ad lib intake at 22
      degrees C). The suppression of sexual receptivity was accompanied by decreases in
      the number of detectable ERIR cells in the ventromedial hypothalamus (VMH) and by
      increases in the number of ERIR cells in the medial preoptic area (mPOA). The
      cold-induced decreases in estrous behavior and in VMH ERIR cells were prevented
      by lesions of the area postrema (AP), but AP lesions did not prevent the
      increases in mPOA ERIR cells. Thus, cold exposure mimics the effects of treatment
      with metabolic inhibitors, experimental diabetes, food deprivation, and insulin
      induced fattening on these endpoints. These findings are consistent with the
      hypothesis that dwelling in the cold affects reproduction indirectly via its
      actions on metabolic fuel availability, rather than by acting directly on
      neuroendocrine processes.

PMID- 10073478
TI  - The influence of olfaction on potentiation and inhibition of ultrasonic
      vocalization of rat pups.
AB  - Twelve-day-old isolated rat pups reduce their rates of ultrasonic vocalization
      (USV) when an anesthetized adult is placed into the test cage, whether the adult
      is their dam or an unfamiliar male. USV rates remain very low even after removal
      of the male (inhibition). However, after removal of the dam, pups greatly
      increase their rates of USV over their first isolation period (potentiation). USV
      potentiation can be induced by either an awake, normally behaving dam or by one
      that is anesthetized. To test the role of olfaction in inhibition and
      potentiation, PND12 pups were rendered anosmic via intranasal infusion of 5% zinc
      sulphate (ZnSO4). Control pups were infused with normal saline. After overnight
      separation from the dam, the USV and other behaviors of pups were recorded during
      a 6-min test. Each pup was tested during an initial isolation period and a final
      isolation period. In the first experiment, an anesthetized adult (dam or
      unfamiliar male) or no companion was placed in contact with the pup during the
      middle minute. Anosmia prevented both potentiation and inhibition of USV by
      passive adult contact. Thus, it seems likely that pups use olfactory
      discrimination as the basis for these two highly differentiated vocal responses
      to social stimuli. Results from two additional experiments demonstrate that
      anosmia does not prevent potentiation when the adult dam is active and
      interacting with the pup on either postnatal day 12 or 8.

PMID- 10073479
TI  - Glossopharyngeal nerve transection reduces quinine avoidance in rats not given
      presurgical stimulus exposure.
AB  - Behavioral studies on the effects of bilateral glossopharyngeal nerve (GL)
      transection on quinine responsiveness have yielded mixed results. These
      differences may be explained by the presence or absence of presurgical exposure
      with the tastant. In the present experiment we measured unconditioned licking to
      quinine in rats that had no exposure to quinine before surgery. Rats were water
      deprived and trained to lick water during 10 s trials in an automated gustometer.
      Next, they were divided into groups that received either GL transection or sham
      surgery (CON). Following recovery, the water-deprived rats were presented with
      seven concentrations of quinine hydrochloride (0.003-3 mM) and distilled water.
      The number of licks to each tastant was averaged over three days of testing. Rats
      with GL transection licked significantly more to the higher concentrations of
      quinine relative to CON rats, resulting in a 0.44 log10 unit shift in the quinine
      concentration-response curve. These results when considered with prior work
      suggest that experience before nerve transection may have a small protective
      effect on taste-guided behavioral responsiveness to quinine in rats.

PMID- 10073480
TI  - Relationship between hyponeophagia and adrenal cortex function in farmed foxes.
AB  - The adrenal cortex function of farmed blue (Alopex lagopus) and silver foxes
      (Vulpes vulpes) differing in their reaction in the feeding test were assessed.
      The urine cortisol:creatinine ratio was lower for those animals eating in the
      feeding test in comparison to those not eating in both species. In addition,
      eater silver foxes had lower baseline serum cortisol concentration and also lower
      serum cortisol concentration 2 h after ACTH administration than noneaters. There
      were no differences in any serum cortisol levels between the eater and noneater
      blue foxes. The weights of body and adrenals did not differ between confident and
      fearful animals in either species. The present study demonstrates that animals
      not eating in the feeding test may have higher fearfulness and be more stressed
      than animals eating.

PMID- 10073481
TI  - Organization of territorial marking behavior by testosterone during puberty in
      male tree shrews.
AB  - According to current hypotheses, in mammals male-specific behavior is organized
      perinatally, and activated in adulthood by male gonadal hormones. However, this
      strict differentiation between early organizational and late activational hormone
      effects has been criticized recently. Around puberty the testosterone levels of
      male mammals rise far above adult levels. In this study we examined the relevance
      of this pubertal testosterone peak on marking behavior of adult tree shrews
      (Tupaia belangeri). Male tree shrews were castrated before puberty and treated
      with testosterone either around puberty or in adulthood. Several months later,
      the marking behavior of the castrated adult animals was examined in standard
      tests in different scent conditions before and after a second testosterone
      treatment. Males castrated as adults as well as fertile females were used as
      controls. The testosterone peak during puberty did not influence male marking
      behavior in the absence of scent from conspecifics (familiarization marking) or
      in the presence of female scent (sexual marking). However, testosterone during
      puberty determined both the male-specific reaction patterns to male scent
      (territorial marking) and the male-specific regulation of this behavior by
      testosterone. These results indicate that testosterone during puberty
      specifically organizes male territorial-marking behavior. To our knowledge, these
      are the first results demonstrating organizational effects of testosterone during
      puberty on male behavior.

PMID- 10073482
TI  - Transient overconsumption of novel foods by deafferentated rats: effects of novel
      diet composition.
AB  - We recently demonstrated that capsaicin-treated rats consume more of an
      unfamiliar high-fat diet than vehicle-treated controls, but only on initial
      exposure (Chavez et al, 1997). We hypothesized that negative feedback signals
      carried by capsaicin-sensitive visceral afferents are critical for the regulation
      of intake of novel foods, but redundant pathways take over during subsequent
      exposures. To examine the role of nutrient content of the novel diet, rats were
      systemically treated with capsaicin (n = 15) or vehicle (n = 10), and exposed to
      1) a fat/olestra diet that was isocaloric with chow; 2) a readily accepted fat
      free cake; and 3) pure corn oil. Each 3-h feeding trial was preceded by 24-h food
      deprivation. Treated rats did not overconsume familiar chow, but did consume 50%
      more than controls of both the fat/olestra diet and the corn oil on first
      exposure; this suggests that capsaicin eliminated visceral afferents that
      normally carry satiety signals. However, the effect with the fat/olestra mixture
      was due primarily to depressed intake by controls, unlike the pure fat diets;
      this apparent neophobic response was blunted in treated rats. Because treated
      rats failed to overconsume the fat-free cakes, the neural system damaged by
      capsaicin appears to be linked to energy or fat sensory mechanisms, and possibly
      to hedonic responsiveness.

PMID- 10073483
TI  - Physostigmine enhances performance on an odor mixture discrimination test.
AB  - Acetylcholine is found within key sectors of the olfactory pathway, and is the
      neurotransmitter for many bulbopetal axons terminating in the glomerular and
      internal plexiform layers of the olfactory bulb. The present study determined
      whether systemically administered physostigmine, a cholinesterase inhibitor,
      alters the rat's ability to discern among odorant mixtures. Following appropriate
      training, the performance of eight rats was measured every third day on an odor
      mixture discrimination test with six levels of difficulty. On each test day
      (separated from one another by 3 days), a different drug treatment was
      administered [i.e., 0.00 (saline), 0.05, 0.10, or 0.20 mg/kg physostigmine]. The
      presentation order of the treatments was counterbalanced across subjects using 4
      x 4 Latin squares. The mixture discrimination test consisted of discerning the
      odor of an airstream coming from the saturated head space of a 1% concentration
      of ethyl acetate from an airstream saturated with a 1% concentration of ethyl
      acetate and various concentrations of butanol (i.e., 1, 0.5, 0.1, 0.05, 0.01, or
      0.005%). Physostigmine was found to enhance odor discrimination performance on
      the more difficult discrimination tasks in a dose-related manner, suggesting that
      cholinergic activation may sharpen the ability of rats to discern subtle
      differences among complex odor stimuli.

PMID- 10073484
TI  - Effects of NMDA lesions of the medial basal forebrain on LH and VTA self
      stimulation.
AB  - Rewarding stimulation of the medial forebrain bundle (MFB) increases Fos-like
      immunoreactivity in many brain areas, including an ipsilateral, basal forebrain
      region extending from the medial preoptic area (MPO) to the lateral preoptic
      area, and substantia innominata. Excitotoxic lesions of the lateral portion of
      this region have been found to produce large sustained or transient increases in
      the number of pulses required to maintain half-maximal lever-pressing (required
      number of pulses) for MFB stimulation. In the present study, changes in self
      stimulation of the lateral hypothalamus and ventral tegmental area were assessed
      following excitotoxic lesions of more medial structures, including the MPO and
      bed nucleus of the stria terminalis. Increases in the required number of pulses
      (up to 0.16 log10 units) were seen in only 2 of 10 subjects. In two other rats,
      the reward effectiveness of the stimulation was moderately increased after the
      lesion as manifested in decreases of up to 0.14 log10 units in the required
      number. No appreciable change from baseline was seen in the remaining six
      subjects. The simplest interpretation of these results is that neurons with cell
      bodies in the medial portion of the basal forebrain may make a smaller
      contribution to the rewarding effect of MFB stimulation than neurons in the
      lateral portion.

PMID- 10073485
TI  - Insulin affects dopamine overflow in the nucleus accumbens and the striatum.
AB  - To better characterize the central nervous system response to peripheral insulin
      administration, male Sprague-Dawley rats were fitted with microdialysis probes in
      the nucleus accumbens (NAC; n = 23) and striatum (STR; n = 22). Awake intact rats
      were injected with either 0, 200, 400, or 600 mU regular insulin i.p. Dopamine
      overflow was measured for at least 2 h postinjection. In the NAC, four
      postinjection samples were collected once every 30 min. In the STR, eight
      postinjection samples were collected, once every 20 min. Dopamine baselines in
      the NAC and STR were 9.22 pg +/- 2.02 and 10.33 pg +/- 2.22 per sample,
      respectively. In the nucleus accumbens, dopamine release was significantly
      greater in the group treated with 600 mU insulin (203 +/- 38% of baseline at 30
      min). In the STR, increased dopamine release was observed in the groups treated
      with 200 and 400 mU insulin, whereas a suppression of a dopamine release was
      observed in the group treated with 600 mU. These data demonstrate that the
      metabolic state induced by peripheral insulin injection causes dopamine
      metabolism to change in both the NAC and STR, and at least in part support the
      hypothesis that insulin may have reinforcing properties in its effect on NAC
      dopamine release.

PMID- 10073486
TI  - Modification of behavioral and neural taste responses to NaCl in C57BL/6 mice:
      effects of NaCl exposure and DOCA treatment.
AB  - To investigate the possible role of peripheral gustatory responsiveness to
      changes in NaCl acceptance, we studied NaCl consumption and the chorda tympani
      nerve responses to lingual application of NaCl in C57BL/6ByJ mice. The mice were
      treated with 300 mM NaCl (given to drink in 96-h two-bottle tests with water) or
      with injections of deoxycorticosterone acetate (DOCA; 33 mg/kg daily). Naive mice
      were neutral to 75 mM NaCl, but mice previously exposed to 300 mM NaCl avoided 75
      mM NaCl. The NaCl-exposed (300 mM for 4 days and 75 mM for 2 days) mice had
      enhanced amiloride-sensitive components of the chorda tympani responses to 10-30
      mM NaCl applied at room temperature (24 degrees C). DOCA injections increased
      acceptance of 300 mM NaCl, but did not change the chorda tympani responses to 100
      1000 mM NaCl. However, the DOCA-treated mice had enhanced amiloride-sensitive
      components of the chorda tympani responses to cold (12 degrees C) 10-30 mM NaCl.
      These data suggest that peripheral gustatory responsiveness possibly contributes
      to the NaCl aversion induced by exposure to concentrated NaCl, but not to the
      DOCA-induced increase of NaCl acceptance.

PMID- 10073487
TI  - Androgens and estrogens modulate 5-HT1A and 5-HT1B agonist effects on aggression.
AB  - Intermale offensive aggressive behavior is facilitated by gonadal steroids and
      inhibited by serotonin (5-HT), presumably through its effects at 5-HT1A and 5
      HT1B receptor sites. To examine the interaction between these neuroendocrine and
      neurochemical regulatory systems, CF-1 male mice were gonadectomized and
      implanted with silastic capsules containing either diethylstilbestrol (DES, a
      synthetic estrogen), the nonaromatizable androgens methyltrienolone (R1881) or
      dihydrotestosterone (DHT), or testosterone (T). Two weeks later, they were given
      8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist; 0.1 or 1.0
      mg/kg), CGS12066B (a 5-HT1B agonist; 4.0 or 8.0 mg/kg), 0.1 or 1.0 mg/kg 8-OH
      DPAT + 4.0 mg/kg CGS12066B, or vehicle, and tested for aggression. In the
      presence of DES, the higher 8-OH-DPAT dose given in combination with CGS
      attenuated aggression in comparison to vehicle controls. When given
      nonaromatizable androgen (R1881 or DHT), all drug treatments except 0.1 mg/kg 8
      OH-DPAT significantly reduced offensive attack behavior. In the presence of T,
      which provides estrogenic and androgenic stimulation, aggression scores were
      significantly reduced when males were given the high dose of 8-OH-DPAT or
      CGS12066B, as well as in the 1.0 mg/kg 8-OH-DPAT + CGS12066B condition.
      Assessments of changes in motor behavior showed significant impairment when 8.0
      mg/kg CGS12066B was administered across all hormonal conditions, indicating that
      reductions in offensive aggression in these treatment groups were nonspecific.
      The results demonstrate differential effects of the steroidal environment on the
      ability of 5-HT1A and 5-HT1B agonists to modulate aggression, with estrogens
      producing a more restrictive environment than androgens for serotonergic
      inhibition of male-typical aggressive behavior.

PMID- 10073488
TI  - Treatment with dexamethasone alters yawning behavior induced by cholinergic but
      not dopaminergic agonist.
AB  - Because stressful manipulations have been reported to modify drug-induced
      yawning, the present study investigated the effects of single and repeated
      treatment with a synthetic glucocorticoid, dexamethasone (DEXA) on apomorphine-
      and pilocarpine-induced yawning in male rats. Neither single nor repeated
      treatment with DEXA altered apomorphine-induced yawning. Single administration of
      DEXA, however, resulted in an increased number of yawns induced by pilocarpine.
      Conversely, repeated administration of DEXA led to a decreased number of yawns
      induced by pilocarpine. In conclusion, the present findings show that
      dopaminergic and cholinergic are distinctly altered by DEXA, in terms of yawning
      behavior when animals received DEXA.

PMID- 10073489
TI  - Prior morphine facilitates the occurrence of immobility and anhedonia following
      stress.
AB  - The role of the activation of the opiate system either induced by a 120-min
      restraint session or by a single morphine administration (10 mg/kg, i.p.) on the
      behaviors performed in a subsequent forced-swim test has been evaluated. In
      addition, animals were pretreated with naloxone (2 mg/kg, i.p.) prior to
      restraint or to morphine. Furthermore, in order to evaluate if this opioid
      mechanism could participate in the effect of stress on the response to a
      rewarding stimulus, rats were administered with morphine (10 mg/kg, i.p.)-
      whether associated or not with prior naloxone (2 mg/kg, i.p.) administration--and
      subsequently exposed to a 90-min restraint period. Following stress, all rats
      were submitted to a sucrose (1%) preference test. Both morphine and restraint
      enhanced the time spent in immobility in the forced-swim test. Both behavioral
      effects were attenuated by naloxone pretreatment thus suggesting that the
      increased immobility is probably modulated by the previous activation of an
      opiate mechanism. Furthermore, only animals with the associated treatment with
      morphine and restraint showed a clear reduction in sucrose preference. The fact
      that this effect was blocked by naloxone suggests the involvement of an opiate
      process in this decreased response to reward. These behavioral data suggest that
      the activation of an endogenous opiate mechanism facilitates the occurrence of
      enhanced immobility and anhedonia in response to a subsequent stress experience.

PMID- 10073490
TI  - Metabolic responses to intracerebroventricular leptin and restricted feeding.
AB  - Leptin is a hormone secreted by adipocytes, which plays an important role in the
      control of food intake and metabolic processes. In the current study, a dose
      dependent relationship was shown between a bolus intracerebroventricular rat
      recombinant leptin administration and reductions in food intake and body weight
      in Sprague-Dawley rats. During the 24 h postinjection period, food intake was
      decreased by 24, 26, and 52% with 0.625, 2.5, and 10 microg of leptin,
      respectively. Body weight was reduced by 2, 3, and 5% at 24 h after leptin
      administration at the doses of 0.156, 2.5, and 10 microg, respectively.
      Furthermore, indirect calorimetry demonstrated that five daily i.c.v. injections
      of leptin resulted in an increase in heat production per unit of metabolic body
      size and fat oxidation by approximately 10 and 48%, respectively. In contrast,
      food-restricted rats that consumed the equivalent amount of food as leptin
      treated rats for 5 days decreased their energy expenditure by 10%. Food
      restriction was found to decrease respiratory quotient in a similar pattern as
      the leptin administration. When ad lib feeding was resumed, food-restricted rats
      quickly recovered their normal food intakes, body weights, and metabolism.
      Conversely, leptin treatment has prolonged effects on body weight resulting from
      different metabolic responses than food restriction. Leptin not only suppresses
      food intake, but also enhances energy expenditure to reduce fat depots.

PMID- 10073491
TI  - Energy intake during reproduction in captive common marmosets (Callithrix
      jacchus).
AB  - Among haplorhine primates, the highly specialized Callitrichidae (marmosets and
      tamarins) are expected to have comparatively high reproductive costs, a feature
      that might be related to the evolution of a cooperative breeding system. Costs of
      reproduction in captivity were investigated on the basis of changes in energy
      intake and body weight during pregnancy and lactation in pair-living female and
      male common marmosets (Callithrix jacchus). The experimental design had little
      effect on carrying behavior, food intake, and body weight of adults, but a
      negative transitory effect of offspring body weight. Increased energetic
      requirements during pregnancy did not result in a higher energy intake in
      females. During lactation, females increased their energy intake up to 100% and
      gradually lost weight, suggesting even higher costs. Extensive carrying behavior
      by males, on the other hand, did not result in an increased energy intake in
      males, or in changes in male body weight. It is suggested that, at least in
      captivity, increased energetic demands during reproduction are reduced by
      behavior allocations towards energetically less expensive behaviors.

PMID- 10073492
TI  - Does exercise affect female hamster gonadotropins by reducing estradiol negative
      feedback?
AB  - Exercise stimulates reproductive function in hamsters exposed to short-day
      photoperiod (SDP) in contrast to its inhibitory effects in women and rats. SDP
      inhibits hamster reproduction in part by increasing the sensitivity of the
      hypothalamo-pituitary-gonadal axis (HPGA) to the negative feedback of gonadal
      steroids. To determine whether EX facilitates reproduction in female hamsters by
      affecting this mechanism, we examined the influence of estradiol (E2) on basal LH
      and FSH concentrations in exercising and sedentary hamsters maintained on long
      day photoperiod (LD 14:10, LDP) or SDP (LD 8:16). In the LDP, serum LH and FSH
      were unaffected or reduced by exercise in ovariectomized (OVX) nonhormone
      replaced hamsters, and LH was increased after tonic E2 replacement compared to
      sedentary controls. In the SDP, serum LH and FSH were significantly higher in OVX
      exercising than in sedentary hamsters, whether the exercisers were injected with
      a high dose of E2 or not. Thus, the effects of exercise on basal gonadotropin
      secretion in female hamsters appear to depend on the level of estradiol negative
      feedback (ENF). When this feedback is low (LDP OVX condition), exercise is either
      ineffective or inhibitory. When the ENF is increased by exposure to SDP and/or by
      treatment with E2, exercise has a stimulatory effect on basal gonadotropin
      secretion. Exercise may stimulate hamster gonadotropin secretion by reducing the
      ENF either by lowering the sensitivity of the HPGA to steroid negative feedback
      or by other means.

PMID- 10073493
TI  - Effect of drugs that alter alertness and emotionality on the novelty response of
      a weak electric fish, Gymnotus carapo.
AB  - Weak field electric fish respond to alerting stimuli with a transient increase in
      the frequency of electric organ discharge (novelty response). In an attempt to
      demonstrate the influence of different degrees of alertness and of emotionality
      on the novelty response of Gymnotus carapo, we studied the variations in the
      magnitude of this response induced by the application of an electric stimulus to
      the water of the experimental box using a pair of electrodes, before and after
      intramuscular injections of d-amphetamine (1-2 and 4 mg/kg), sodium pentobarbital
      (10-20 and 30 mg/kg), diazepam (1-2 and 4 mg/kg), beta-carboline (2 mg/kg), and
      saline. After d-amphetamine injection the animal presented increased somatic
      motility but no changes in electric organ baseline firing rate or in response to
      the alerting electric stimulus. Sodium pentobarbital induced a partial loss of
      posture and a reduction of fin and operculum movements, as well as a reduction of
      baseline firing rate and of the response to the alerting electric stimulus, with
      frequent interruptions in electric organ firing. Beta-carboline caused increased
      motility, but no changes in basal firing rate or in response to the alerting
      stimulus. Diazepan-injected fishes remained still throughout the experiment, and
      some of those threated with the higher dose (4 mg/kg) presented interruptions on
      electric organ discharges in response to stimulation but no change on baseline
      firing rate. The data suggest that a reduction of the degree of alertness by the
      barbiturate and a decrease in emotionality and/or stress by the benzodiazepine
      interfere with the novelty response. The possible site of action of the drugs is
      discussed.

PMID- 10073494
TI  - Dehydration-associated anorexia: development and rapid reversal.
AB  - Dehydration in rats results in anorexia that is proportional to the degree of
      dehydration. The aims of this study were first, to determine when anorexia
      develops in response to drinking hypertonic (2.5%) saline for 4 days; and second,
      to determine the organization of ingestive behaviors after access to water is
      resumed. Body weights, food, and fluid intake were measured morning and evening
      before, during, and after a 4-day period of dehydration caused by drinking
      hypertonic saline. A profile of the behaviors expressed immediately after
      rehydration was determined. The data make three points. First, dehydration
      associated anorexia does not emerge until the second night of dehydration when
      the composition of the fluid compartments can no longer be homeostatically
      buffered. Second, dehydration reduces the amount food eaten nocturnally, but
      leaves diurnal food consumption largely unaffected. Animals very rapidly return
      to predehydration nocturnal ingestion patterns, whereas the amounts of food and
      water ingested during the day are significantly increased. Increased diurnal food
      intake may play a significant role in normalizing metabolism after dehydration.
      Finally, anorexia is reversed within minutes of rehydration. The data suggest a
      model where dehydration simultaneously activates two sets of circuits within the
      brain that will independently stimulate or inhibit feeding. Eating is inhibited
      during dehydration through the action of a set of inhibitory circuits, which
      masks the output of circuits that stimulate eating. However, when drinking water
      resumes, sensory inputs to these circuits rapidly release the inhibition and
      allow eating to proceed freely.

PMID- 10073495
TI  - Body fluid distribution in rats with cold-induced hypertension.
AB  - The purpose of this experiment was to determine body fluid distribution during
      chronic cold exposure and to further understand the mechanism of cold-induced
      hypertension. Blood pressures, hematocrit, and the plasma, blood, and
      extracellular fluid volumes were measured in rats at intervals of 1, 3, and 5
      weeks after exposure to cold (5 degrees C). Resting systolic, diastolic, and mean
      blood pressures measured by direct arterial cannula were significantly elevated
      in a time-dependent manner over the duration of cold exposure. The increase in
      diastolic blood pressure, which reflects the peripheral vascular resistance,
      exceeded that of systolic blood pressure after both 3 and 5 weeks of exposure to
      cold. Pulse pressure was significantly decreased by 3 and 5 weeks of cold
      exposure. The plasma, blood, and extracellular fluid volumes were significantly
      increased after both 1 and 3 weeks of exposure to cold, but had returned to
      control levels by 5 weeks of cold exposure. Cold exposure, however, did not
      affect the hematocrit. The 2-h water intake after the cold-exposed rats were
      returned to warm (25 degrees C) (thermogenic drinking) was significantly
      increased compared to that of warm-acclimated rats during the first, third, and
      fifth week of exposure to cold. The present results suggest that the development
      of cold-induced hypertension is associated with blood volume expansion, and that
      the elevated blood pressure is maintained by increased peripheral vascular
      resistance without blood volume expansion. The results also imply that exposure
      to cold induces a dehydration in rats.

PMID- 10073496
TI  - Hepatic portal vein cannulation for infusion and blood sampling in freely moving
      rats.
AB  - Chronic portal vein cannulation in the rat is an important technique to study
      secretory rates of hormones from the endocrine pancreas. Moreover, it can be used
      for studying the effects of enteric hormones and pharmaca on behavioral and
      physiological processes. This article contains an extensive description of a
      cannulation technique of the portal vein that has many advantages over those
      reported so far in the literature, and that was very successful in several
      behavioral and physiological studies during the last decade.

PMID- 10073497
TI  - Gender influences the core temperature response to a simulated open field in
      adult guinea pigs.
AB  - The induction of psychological stress is often accompanied by a transient
      increase in core temperature, commonly referred to as stress induced
      hyperthermia. Although stress-induced hyperthermia occurs when rats, mice, and
      pigs are exposed to a novel stimulus (e.g., a simulated open field, restraint,
      etc.), whether or not it occurs in guinea pigs has not been investigated. The
      present experiments were therefore carried out to investigate the
      thermoregulatory responses of both male (n = 7) and female (n = 7) adult guinea
      pigs when they were exposed to a simulated open field. Unexpectedly, neither the
      male nor female guinea pigs developed stress-induced hyperthermia. To the
      contrary, female but not male guinea pigs significantly decreased their core
      temperature during an open field experiment. The mechanism of the gender-specific
      thermoregulatory response of the adult guinea pig to psychological stress is
      presently unknown.

PMID- 10073498
TI  - Effect of diet textural characteristics on the temporal rhythms of feeding in
      rats.
AB  - To examine whether the diurnal rhythms of protein-rich and carbohydrate-rich diet
      ingestion can be altered by presenting the diets in different textural forms,
      adult male Wistar rats were assigned to two dietary groups. One group received a
      two-way choice between high-protein powder and high-carbohydrate granular (HPP
      HCG) diets. In the other group the textures were reversed [high-protein granular
      and high-carbohydrate powder (HPG-HCP) diets]. Rats fed HPP-HCG diets selected
      significantly less protein (kcal) vs. rats fed HPG-HCP diets, during the 24-h and
      12-h dark phase and during the 4-h early and late dark phases. Carbohydrate
      intakes of the two dietary groups were not significantly different. Total caloric
      intake for the HPG-HCP dietary group was significantly higher than that of the
      HPP-HCG dietary group during the 24-h and 12-h dark phase. Body weight was
      significantly lower in rats fed HPP-HCG diets. In conclusion, macronutrient-rich
      diets presented in different textural forms alter protein-rich diet ingestion and
      total energy intake.

PMID- 10073499
TI  - Neuropeptide Y-related compounds and feeding.
AB  - Neuropeptide Y (NPY) and related compounds increase short-term feeding. Previous
      studies have used different animal models, feeding schedules, sources of the
      compounds, and time and routes of administration. These differences in
      methodology are important in the variability reported on the potency of NPY
      related compounds. To obtain reliable data on the relative efficacy, we tested
      NPY, NPY 3-36, and pancreatic polypeptide (PP) using an identical protocol and
      the same commercial source. These three NPY-related compounds were tested using
      the intracerebroventricular (i.c.v., into the third ventricle) administration,
      and the profile of the feeding enhancement including the dose response and
      potency was determined. Compounds were tested in parallel on at least 2
      successive days. NPY, NPY 3-36, and PP exhibited different potencies in enhancing
      2-h food intake. Comparison of their dose responses (using 0.1, 0.25, 0.5, 1.0,
      2.5, and 5.0 microg/rat) demonstrated an overall potency of NPY 3-36 > NPY > PP
      for the high doses. To study ligand interactions, we examined the effects of
      various combinations of NPY-related compounds administered concomitantly. These
      combinations were justified based on the data obtained from the individual dose
      responses. The data show that the effects of NPY plus NPY 3-36 or NPY 3-36 plus
      PP were less than additive. When compared to the individual responses, the
      effects of NPY 3-36 were almost identical to those induced by the combinations
      using low doses of NPY plus NPY 3-36, or low and high doses of PP plus NPY 3-36.
      The results support the notion that NPY and its analogues induce a short-term
      feeding response by activating multiple receptor subtypes.

PMID- 10073500
TI  - The pathobiology of osteoarthritis and the rationale for the use of pentosan
      polysulfate for its treatment.
AB  - OBJECTIVES: Structure-modifying osteoarthritis (OA) drugs (SMOADs) may be defined
      as agents that reverse, retard, or stabilize the underlying pathology of OA,
      thereby providing symptomatic relief in the long-term. The objective of this
      review was to evaluate the literature on sodium pentosan polysulfate (NaPPS) and
      calcium pentosan polysulfate (CaPPS), with respect to the pathobiology of OA to
      ascertain whether these agents should be classified as SMOADs. METHODS: Published
      studies on NaPPS and CaPPS were selected on the basis of their relevance to the
      known pathobiology of OA, which also was reviewed. RESULTS: Both NaPPS and CaPPS
      exhibit a wide range of pharmacological activities. Of significance was the
      ability of these agents to support chondrocyte anabolic activities and attenuate
      catabolic events responsible for loss of components of the cartilage
      extracellular matrix in OA joints. Although some of the anti-catabolic activities
      may be mediated through direct enzyme inhibition, NaPPS and CaPPS also have been
      shown to enter chondrocytes and bind to promoter proteins and alter gene
      expression of matrix metalloproteinases and possibly other mediators. In rat
      models of arthritis, NaPPS and CaPPS reduced joint swelling and inflammatory
      mediator levels in pouch fluids. Moreover, synoviocyte biosynthesis of high
      molecular-weight hyaluronan, which is diminished in OA, was normalized when these
      cells were incubated with NaPPS and CaPPS or after intraarticular injection of
      NaPPS into arthritic joints. In rabbit, canine, and ovine models of OA, NaPPS and
      CaPPS preserved cartilage integrity, proteoglycan synthesis, and reduced matrix
      metalloproteinase activity. NaPPS and CaPPS stimulated the release of tissue
      plasminogen activator (t-PA), superoxide dismutase, and lipases from vascular
      endothelium while concomitantly decreasing plasma levels of the endogenous
      plasminogen activator inhibitor PAI-1. The net thrombolytic and lipolytic effects
      exhibited by NaPPS and CaPPS may serve to improve blood flow through subchondral
      capillaries of OA joints and improve bone cell nutrition. In geriatric OA dogs,
      NaPPS and CaPPS reduced symptoms, as well as normalized their thrombolytic
      status, threshold for platelet activation, and plasma triglyceride levels. These
      hematologic parameters were shown to be abnormal in OA animals before drug
      treatment. Similar outcomes were observed in OA patients when CaPPS or NaPPS were
      given orally or parenterally in both open and double-blind trials. CONCLUSIONS:
      The data presented in this review support the contention that NaPPS and CaPPS
      should be classified as SMOADs. However, additional long-term clinical studies
      employing methods of assessing joint structural changes will be needed to confirm
      this view.

PMID- 10073501
TI  - Production and elimination of hyaluronan in rheumatoid arthritis patients:
      estimation with a loading test.
AB  - OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate
      (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal
      HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the
      compatibility of a new model for HYA kinetics, taking renal elimination into
      separate account in the overall clearance of HYA from the blood. METHODS: The
      calculations of production and elimination of HYA were based on the HYA loading
      test, which was performed in 21 patients with RA and 15 healthy controls. A blood
      sample was drawn before the loading test, followed by an intravenous (i.v.)
      injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken
      regularly during the next 60 minutes. A theoretical model with computational
      analysis of the data collected was used for calculating HYA production and
      elimination. RESULTS: Patients with RA had significantly higher c0 than healthy
      controls, although in 10 of 21 patients c0 was within the normal range. The RA
      patients also had higher Vmax than healthy controls, but the difference was not
      significant. The calculated production of HYA was increased in RA patients (P =
      .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in
      which the renal elimination was taken separately into account, proved to be more
      compatible than the previous model. CONCLUSION: The HYA loading test can help
      determine whether the increased serum level of HYA in RA patients is due to a
      high production or reduced elimination of HYA or both.

PMID- 10073502
TI  - Takayasu's arteritis presenting as fever of unknown origin: report of two cases
      and literature review.
AB  - OBJECTIVES: This study reports two patients with Takayasu's arteritis presenting
      with a fever of unknown origin (FUO) and reviews the literature on that
      association. METHODS: We describe the clinical presentation, course, and outcome
      of the two patients, and reviewed the medical literature from 1968 till 1997
      using MEDLINE and the key words fever, diagnosis, and Takayasu's arteritis.
      RESULTS: Takayasu's arteritis is rarely reported as a cause of FUO. Noninvasive
      diagnostic techniques such as magnetic resonance imaging, computed tomography
      scanning, gallium-67 scintigraphy, and ultrasonography may help in the diagnosis
      of Takayasu's arteritis in the prepulseless stage. CONCLUSION: Takayasu's
      arteritis should be considered in the differential diagnosis of FUO, especially
      in young women.

PMID- 10073503
TI  - The perils of paediatric research.

PMID- 10073504
TI  - Meat and cancer: a relation in search of a mechanism.

PMID- 10073505
TI  - Assessment of genetic markers for coronary thrombosis: promise and precaution.

PMID- 10073506
TI  - Genetic control of anticoagulation.

PMID- 10073507
TI  - Yoga in treatment of carpal-tunnel syndrome.

PMID- 10073508
TI  - Iron pots for cooking: wishful thinking or traditional common sense?

PMID- 10073509
TI  - Blood transfusion: Bayer's initiative.

PMID- 10073510
TI  - Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control
      study.
AB  - BACKGROUND: Apart from the small number of iatrogenic and familial cases, the
      cause of most cases of Creutzfeldt-Jakob disease (CJD) is not known. We aimed to
      identify risk factors for sporadic CJD. METHODS: In a case-control study, we
      compared the medical history and selected demographic characteristics of 241
      definite (neuropathologically confirmed) and probable (clinically likely)
      patients with CJD, ascertained from the Australian National Creutzfeldt-Jakob
      Disease Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls,
      recruited from the community by random telephone interview in August, 1997.
      Standard logistic regression was used for the comparisons. FINDINGS: Surgical
      procedures were significantly associated with the development of sporadic CJD.
      This risk progressively increased with the number of surgical treatments to a
      maximum for three procedures (odds ratio 2.13 [95% Cl 1.34-3.41], p=0.002). There
      was also a significant association between risk of CJD and residence or
      employment on a farm (p<0.001) or market garden (p=0.002) for longer than 10
      years. We found no significant risk associated with a history of blood
      transfusion, organ transplantation, major dental work, or occupation.
      INTERPRETATION: Our findings accord with the hypothesis that a range of surgical
      treatments may serve as unrecognised contamination events and account for a
      proportion of cases of sporadic CJD. Possible biases in different methods and
      times for the acquisition of data on cases and controls suggest our findings need
      to be replicated in independent studies with community controls.

PMID- 10073511
TI  - Comparison of three single doses of mifepristone as emergency contraception: a
      randomised trial. Task Force on Postovulatory Methods of Fertility Regulation.
AB  - BACKGROUND: Mifepristone is a highly effective and well-tolerated emergency
      contraceptive when given in a dose of 600 mg within 72 h of unprotected coitus.
      We assessed whether the same effectiveness can be achieved with lower doses of
      mifepristone (50 mg and 10 mg) and a longer postcoital treatment period (120 h).
      METHODS: We undertook a multicentre, single-masked, randomised trial in 11 family
      planning clinics in Australia, China, Finland, Georgia, the UK, and the USA. 1717
      healthy women with regular menstrual cycles who requested emergency contraception
      within 120 h of unprotected coitus were randomly assigned to three treatment
      groups. FINDINGS: 32 women were lost to follow-up and one was pregnant before
      treatment. The 600 mg, 50 mg, and 10 mg groups did not differ in the proportions
      of pregnancies (seven [1.3%] of 559, six [1.1%] of 560, and seven [1.2%] of 565).
      Two pregnancies (both in the 50 mg group) were tubal. Among women without further
      acts of intercourse, treatment delay did not appear to influence the
      effectiveness. No major side-effects occurred, except a delay in the onset of
      next menses, significantly (p<.001) related to the mifepristone dose.
      INTERPRETATION: Lowering the dose of mifepristone sixty-fold did not decrease its
      effectiveness as an emergency contraceptive under typical use, though a study of
      this size cannot exclude differences in effectiveness up to almost three-fold.
      Lower doses of mifepristone were associated with less disturbance of the
      menstrual cycle. Thus, a dose as low as 10 mg seems preferable to the 600 mg
      dose.

PMID- 10073512
TI  - Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney:
      a population-based study.
AB  - BACKGROUND: Heterocyclic amines formed in cooked meat and fish are carcinogenic
      in animal models and form DNA adducts in human beings. We undertook a study to
      assess whether these substances are related to the risks of cancer in the large
      bowel and urinary tract. METHODS: In a population-based case-control study, cases
      were identified from the Swedish cancer registry. Controls were randomly selected
      from the population register. Information on intake of various foods and
      nutrients was assessed by questionnaire, with photographs of foods cooked at
      various temperatures. We measured the content of heterocyclic amines in foods
      cooked under these conditions. FINDINGS: Information was retrieved from 553
      controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of
      bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for
      controls and 70% for cases. The estimated daily median intake of heterocyclic
      amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with
      cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk
      for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95%
      CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for
      bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no
      controls, had an estimated daily intake of heterocyclic amines above 1900 ng.
      INTERPRETATION: Intake of heterocyclic amines, within the usual dietary range in
      this study population, is unlikely to increase the incidence of cancer in the
      colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are
      consistent with human carcinogenicity, but the precision was extremely low.

PMID- 10073513
TI  - A1/A2 polymorphism of glycoprotein IIIa and association with excess procedural
      risk for coronary catheter interventions: a case-controlled study.
AB  - BACKGROUND: A five-fold increase in risk of stent thrombosis in carriers of A1/A2
      (Leu33Pro) polymorphism of glycoprotein Illa has been described. Whether this
      increased procedural risk applies to other coronary interventions is unknown. We
      investigated the role of A1/A2 polymorphism as a putative risk factor. METHODS:
      We genotyped 1000 consecutive patients with angiographically confirmed coronary
      artery disease and 1000 controls matched for age and sex. 653 of the 1000
      patients received interventions (271 coronary angioplasty, 102 directional
      coronary atherectomy, and 280 stenting) and were assessed for a 30-day composite
      endpoint of need for target-vessel revascularisation, myocardial infarction, and
      death. FINDINGS: The composite endpoint occurred in 41 (6.3%) patients. There was
      no evidence that the A2 allele was associated with excess procedural risk
      (relative risk 1.36 [95% CI 0.70-2.70], p=0.37). Nor, in subgroup analyses, did
      A2 predict events that complicated coronary angioplasty (1.17 [0.40-2.70]),
      directional coronary atherectomy (1.50 [0.30-8.70]), or stenting (1.45 [0.60
      3.50]). Neither heterozygotes (A1/A2) nor homozygotes (A2/A2) were over
      represented in any subgroup, including those with acute coronary syndromes, early
      disease manifestation (age <40 years), and histories of myocardial infarction.
      INTERPRETATION: A1/A2 polymorphism is not a major risk factor for 30-day adverse
      events that complicate coronary angioplasty, directional coronary atherectomy, or
      stenting. Furthermore, A1/A2 polymorphism has no apparent impact on more chronic
      processes such as atherogenesis of the coronary arteries.

PMID- 10073514
TI  - Effect of consumption of food cooked in iron pots on iron status and growth of
      young children: a randomised trial.
AB  - BACKGROUND: In less-developed countries, novel strategies are needed to control
      iron-deficiency anaemia, the most common form of malnutrition. METHODS: We
      undertook a community-based randomised controlled trial to assess the effects of
      iron or aluminium cooking pots in young Ethiopian children. Analysis was by
      intention-to-treat. The primary outcomes were change in children's haemoglobin
      concentration, weight, or length over the study period. We also did a laboratory
      study of total and available iron in traditional Ethiopian foods cooked in iron,
      aluminium, and clay pots. FINDINGS: 407 children, one per household, entered the
      study. The change in haemoglobin concentration was greater in the iron-pot group
      than in the aluminium-pot group (mean change to 12 months 1.7 [SD 1.5] vs 0.4
      [1.0] g/dL; mean difference between groups 1.3 g/dL [95% Cl 1.1-1.6]). The mean
      differences between the groups in weight and length gain to 12 months (adjusted
      for baseline weight or length) were 0.6 cm (95% CI 0.1-1.0) and 0.1 kg (-0.1 to
      0.3). The laboratory study showed that total and available iron was greatest in
      foods cooked in iron pots, except for available iron in legumes for which there
      was no difference between types of pot. INTERPRETATION: Ethiopian children fed
      food from iron pots had lower rates of anaemia and better growth than children
      whose food was cooked in aluminium pots. Provision of iron cooking pots for
      households in less-developed countries may be a useful method to prevent iron
      deficiency anaemia.

PMID- 10073515
TI  - Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose
      requirement and risk of bleeding complications.
AB  - BACKGROUND: The cytochrome P450 CYP2C9 is responsible for the metabolism of S
      warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild
      type CYP2C9*1 by a single aminoacid substitution in each case. The allelic
      variants are associated with impaired hydroxylation of S-warfarin in in-vitro
      expression systems. We have studied the effect of CYP2C9 polymorphism on the in
      vivo warfarin dose requirement. METHODS: Patients with a daily warfarin dose
      requirement of 1.5 mg or less (low-dose group, n=36), randomly selected patients
      with a wide range of dose requirements from an anticoagulant clinic in north-east
      England (clinic control group, n=52), and 100 healthy controls from the community
      in the same region were studied. Genotyping for the CYP2C9*2 and CYP2C9*3 alleles
      was done by PCR analysis. Case notes were reviewed to assess the difficulties
      encountered during the induction of warfarin therapy and bleeding complications
      in the low-dose and clinic control groups. FINDINGS: The odds ratio for
      individuals with a low warfarin dose requirement having one or more CYP2C9
      variant alleles compared with the normal population was 6.21 (95% CI 2.48-15.6).
      Patients in the low-dose group were more likely to have difficulties at the time
      of induction of warfarin therapy (5.97 [2.26-15.82]) and have increased risk of
      major bleeding complications (rate ratio 3.68 [1.43-9.50]) when compared with
      randomly selected clinic controls. INTERPRETATION: We have shown that there is a
      strong association between CYP2C9 variant alleles and low warfarin dose
      requirement. CYP2C9 genotyping may identify a subgroup of patients who have
      difficulty at induction of warfarin therapy and are potentially at a higher risk
      of bleeding complications.

PMID- 10073516
TI  - Misleading hyperprolactinaemia in pregnancy.

PMID- 10073517
TI  - Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Task
      Force on Postovulatory Methods of Fertility Regulation.

PMID- 10073518
TI  - Isolation of vancomycin-resistant enterococci from animal feed in USA.

PMID- 10073519
TI  - Monocytic Ehrlichia in Ixodes persulcatus ticks from Perm, Russia.

PMID- 10073520
TI  - A potent pressor response elicited by drinking water.

PMID- 10073521
TI  - Stereotactic treatment of Gilles de la Tourette syndrome by high frequency
      stimulation of thalamus.

PMID- 10073522
TI  - Fertility outcome after systemic methotrexate and laparoscopic salpingostomy for
      tubal pregnancy.

PMID- 10073523
TI  - Churg-Strauss syndrome after zafirlukast in two patients not receiving systemic
      steroid treatment.

PMID- 10073524
TI  - Survey in France of response to xenotransplantation.

PMID- 10073525
TI  - New possibilities for prenatal diagnosis of muscular dystrophies: forced
      myogenesis with an adenoviral MyoD-vector.

PMID- 10073526
TI  - Brother and sister with different vasculitides.

PMID- 10073527
TI  - What is all the hullabaloo about endostatin?

PMID- 10073528
TI  - Planning and measuring basic research.

PMID- 10073529
TI  - Funding authority interferes with sexual-health services.

PMID- 10073530
TI  - Haemodialysis.
AB  - This paper charts the development of haemodialysis, the cornerstone of renal
      replacement therapy (RRT). It has enabled patients with end-stage renal failure
      to survive for years, in many cases with a surprisingly good quality of life.
      Through technological advances, RRT can be offered to patients who are older and
      more frail. Many have intercurrent comorbid illness. Such patients can have good
      quality of life, but their survival is shorter since they are likely to succumb
      early to comorbid illnesses. The challenge to nephrologists is to provide
      treatment based on exacting standards for all those patients who can benefit, yet
      to maintain cost-effectiveness. There is increasing recognition that, however
      good the technology underpinning dialysis, what justifies the cost and commitment
      that dialysis entails is the provision for the patient of a satisfactory quality
      of life.

PMID- 10073531
TI  - Can randomised trials inform clinical decisions about individual patients?

PMID- 10073532
TI  - Aflatoxin B1-induced hepatic steatosis: role of carbonyl compounds and active
      diols on steatogenesis.
AB  - Aflatoxin B1 (AFB1) exerts a chronic carcinogenic and an acute toxic effect on
      animals. Whereas the mechanism for carcinogenicity is known, no mechanism has
      been proposed for the toxic action. Among the most prominent signs of
      aflatoxicosis in several species, including birds and mammals, are
      hypolipidaemia, hypocholesterolaemia, and hypocarotenaemia, associated with
      severe hepatic steatosis and weight loss. We suggest that these signs of acute
      imbalance of lipid metabolism can be the result of the chemical modification
      (blocking) of key lysyl residues on the LDL protein B-100 by the activated AFB1
      molecule. Modified LDLs are not recognised by their specific receptors and thus
      are rejected by peripheral cells. Upon return to the liver, the modified
      particles bind to the sinusoidal lining cells. Lipid starvation of peripheral
      tissues takes place while fat accumulates in the liver. This abnormal state is
      maintained and reinforced by further modification of nascent apoproteins, which
      in turn become unable to receive a lipid load for as long as aflatoxin continues
      to be available in the liver.

PMID- 10073533
TI  - Unexplained deaths in infancy.

PMID- 10073534
TI  - Unexplained deaths in infancy.

PMID- 10073535
TI  - Increased cytokines and pamidronate-induced bone pain in adults with cystic
      fibrosis.

PMID- 10073536
TI  - Cerebral hypoxia after cardiopulmonary resuscitation.

PMID- 10073537
TI  - Cerebral hypoxia after cardiopulmonary resuscitation.

PMID- 10073538
TI  - Cerebral hypoxia after cardiopulmonary resuscitation.

PMID- 10073539
TI  - Can a parent with balanced Robertsonian translocation t(21q;21q) have a non
      Down's offspring?

PMID- 10073540
TI  - Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in
      childhood.

PMID- 10073541
TI  - Ataxia telangiectasia gene mutations and chronic lymphocytic leukaemia.

PMID- 10073542
TI  - Increased peroneal nerve injuries caused by ski edges.

PMID- 10073543
TI  - Lead poisoning and psychomotor delay in Bangladeshi children.

PMID- 10073544
TI  - Parvovirus B19 infection and fulminant hepatitis.

PMID- 10073545
TI  - WHO's DOTS strategy. Directly observed therapy.

PMID- 10073546
TI  - WHO's DOTS strategy. Directly observed therapy.

PMID- 10073547
TI  - Wayward patient's commitment to directly observed preventive therapy.

PMID- 10073548
TI  - Personal stereos and hearing loss.

PMID- 10073549
TI  - Thromboprophylaxis for atrial fibrillation.

PMID- 10073550
TI  - Ivermectin distribution for onchocerciasis in Africa.

PMID- 10073551
TI  - Jehovah's Witnesses and blood transfusion.

PMID- 10073552
TI  - Advertising claims for The Lancet.

PMID- 10073553
TI  - The leprosy of Henry VII: incarceration or isolation?

PMID- 10073554
TI  - The Nobel chronicles. 1943: Henrik Carl Peter Dam (1895-1976); and Edward
      Adelbert Doisy (1893-1986).

PMID- 10073555
TI  - Sketches from The Lancet. Hospital food.

PMID- 10073556
TI  - Should autologous or allogeneic stem-cell therapy be a part of consolidation
      therapy for all cases of adult acute myelogenous leukemia?

PMID- 10073557
TI  - Introduction: dose-intensive therapy for adult malignancies.

PMID- 10073558
TI  - Dose-intensive therapy for adult acute lymphoblastic leukemia.
AB  - Major challenges remain to be overcome to increase the cure rate for acute
      lymphoblastic leukemia (ALL), especially for middle-aged and older adults.
      Despite high rates of complete remission (CR), many patients relapse after
      chemotherapy alone. Dose-intensive therapy and stem-cell transplantation (SCT)
      have been able to rescue some of these patients. However, many patients presently
      are being cured using intensive consolidation chemotherapy during first remission
      (CRI) and at a lower cost and toxicity than with SCT. The use of SCT in CRI
      should be governed by an assessment of known risk factors. Among younger adults
      in the prime transplant age group (< 50 years), there is no advantage to
      allogeneic (allo)-SCT across the board, but it is recommended for those with
      Philadelphia chromosome-positive (Ph+) ALL or pro-B ALL with t(4;11) and possibly
      for those with B-lineage ALL and initial WBC counts > 100,000/microL. There is as
      yet no evidence that allo-SCT can improve the already high cure rate achieved
      with chemotherapy alone in favorable subsets such as T-cell ALL. There appears to
      be no advantage to autologous (auto)-SCT over chemotherapy for consolidation of
      either high-risk or standard-risk patients in CRI. The argument that early use of
      auto-SCT shortens the duration of treatment and thereby improves the quality of
      life is not persuasive, as there is little morbidity from maintenance
      chemotherapy. Patients who receive a modern, intensive multiagent chemotherapy
      program for CRI but later relapse are unlikely to be cured with additional
      chemotherapy alone. High-grade multidrug resistance develops rapidly. These
      patients should undergo allo-SCT if possible. Unfortunately, allo-SCT is
      available to only a minority of such patients because of the lack of a donor or
      insurance coverage, or the presence of comorbid conditions or older age. The use
      of alternative donors (either matched, unrelated donors or partially human
      leukocyte antigen [HLA] matched family members) is appropriate in this
      circumstance. Auto-SCT with or without previously used purging methods is
      ineffective for patients with advanced ALL.

PMID- 10073559
TI  - Stage-specific application of allogeneic and autologous marrow transplantation in
      the management of acute myeloid leukemia.
AB  - Allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) have
      become standard approaches for the management of adults with acute myeloid
      leukemia (AML). The indications for transplantation remain controversial as
      parallel improvements in intensive chemotherapy have resulted in excellent
      outcomes for many patients. AlloBMT is the therapy of choice for patients who
      fail to respond to induction chemotherapy. For those patients in first remission
      (CRI), a policy of intensive postremission chemotherapy with transplantation upon
      relapse appears to be optimal. There are no data to support transplantation in
      CRI, allogeneic or autologous, for those patients with leukemia characterized by
      favorable cytogenetic abnormalities [ie, core-binding factor type or t(15;17)],
      as these patients do well with nonmyeloablative strategies. Patients with
      relapsed disease appear to be best served with allogeneic transplantation from a
      human leukocyte antigen (HLA)-matched sibling or one-antigen-mismatched family
      member, whereas for those patients lacking a related donor, unrelated donor
      alloBMT or ABMT provides similar long-term overall survival. Randomized studies
      for the optimal management of relapsed disease are lacking but are needed. The
      objective of this review is to discuss the data supporting the use of alloBMT or
      ABMT at various points during the course of de novo adult AML.

PMID- 10073560
TI  - High-dose therapy for breast cancer.
AB  - In recent years, the most frequent indication for high-dose autologous stem-cell
      supported chemotherapy in the United States has been breast cancer. This approach
      is applied in "high-risk," early-stage disease as adjuvant treatment, and with
      either curative or palliative intent in metastatic disease. Among both lay
      persons and medical professionals, high-dose therapy is broadly viewed as
      standard and appropriate, even though the results of the largest prospective
      randomized studies are not yet available. This view is based on extrapolation
      from preclinical data, a fundamental belief that "more is better," a faith in
      high technology, and the results of numerous pilot and phase I and II trials.
      Because high-dose therapy is promising, but also more difficult to administer
      than standard therapy, controversy rages in all circles concerning its use.
      Unless and until we have the results of properly randomized, prospective studies,
      this controversy will likely continue. Against this background, we will review
      the theoretical basis for high-dose treatment in breast cancer, the translation
      of this laboratory science into the clinic, usual treatment approaches, the
      available data, ongoing clinical trials, and future research directions.

PMID- 10073561
TI  - Stem-cell transplantation in chronic lymphocytic leukemia: the time for designing
      randomized studies has arrived.
AB  - Stem-cell transplantation in conjunction with myeloablative therapy has evolved
      as a standard treatment option for patients with several hematologic
      malignancies, including chemosensitive, relapsed non-Hodgkin's lymphoma and
      untreated multiple myeloma. The pharmacologic basis for this treatment includes a
      favorable tumor dose-response curve that abrogates intrinsic drug resistance
      associated with these diseases and facilitates cure or prolongation of survival
      even in the absence of a cure. The belief that chronic lymphocytic leukemia (CLL)
      is a palliative disease of the elderly has been perpetuated, limiting the
      application of more aggressive therapies. The introduction of fludarabine and its
      use in combination with other agents has increased the morphologic complete
      response rate observed in the initial treatment of CLL, providing the rationale
      to explore further disease-consolidative therapies. Concomitant with this,
      several phase II studies have demonstrated the feasibility of performing both
      allogeneic and autologous stem-cell transplantation in patients with CLL. In this
      regard, allogeneic transplantation has produced prolonged remissions in young
      patients with relapsed and refractory CLL, but at the cost of high treatment
      related morbidity and mortality. Application of "minitransplantation" regimens
      may temper the frequency of these complications and warrants further study.
      Autologous stem-cell transplantation has also been explored with promising
      disease-free survival outcomes in less heavily pretreated patients. However,
      relapses continue to be the most frequent source of late mortality, as has been
      observed previously with multiple myeloma. With scientific justification
      established in similar diseases and demonstrated feasibility with low morbidity,
      we believe the time for a randomized comparison of standard chemotherapy versus
      autologous stem-cell transplantation in CLL has arrived. Despite promising
      results observed with allogeneic transplantation, further refinements that
      broaden the patient eligibility and lower treatment mortality will be required
      before similar investigations can occur with this modality.

PMID- 10073562
TI  - Progenitor cell transplantation for chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML), a myeloproliferative disorder characterized
      by the clonal proliferation of a hematopoietic stem cell, is a malignancy for
      which allogeneic bone marrow transplantation (BMT), when available, constitutes a
      mainstay of treatment. Several clinical considerations, especially the patient's
      age, influence the availability and likely outcome of BMT for patients with CML.
      Recent advances in nontransplant treatments for CML, notably interferon-alpha,
      have made the decision about the implementation and timing of BMT in CML more
      complex. Areas of active investigation include transplantation from a matched
      unrelated donor (MUD) and autologous BMT.

PMID- 10073563
TI  - Hodgkin's disease and transplantation: a room with a (nontransplanter's) view.
AB  - Hodgkin's disease is a malignancy curable by combination chemotherapy in newly
      diagnosed patients. Management of refractory disease or relapse has been
      unsatisfactory with salvage chemotherapy alone, although some patients with long
      initial remission can be cured with this approach. Because correlations between
      dose intensity and response to treatment in animal models and in clinical studies
      have been positive, high-dose chemotherapy (HDT) with bone marrow (BM) or
      peripheral blood stem-cell (PBSC) transplantation support has been used in an
      attempt to improve disease-free and overall survival in patients with refractory
      disease or relapse. Controversy exists over who and when to transplant. Results
      are difficult to interpret because of the heterogeneous nature of the patients
      under study and short follow-up times. In general, patient disease-free and
      overall survival appear to be improved with HDT and PBSC support when compared
      with historical controls. Allografting has also been tried in Hodgkin's disease
      as well, but is not recommended due to high associated mortality. Improvements in
      supportive care for transplantation in general, and antiviral and graft-versus
      host disease prophylaxis in particular, have decreased early mortality associated
      with allografting in other malignancies, but not yet in Hodgkin's disease. The
      fact that allografted patients who survive the initial transplant procedure have
      an impressively lower relapse rate makes Hodgkin's disease patients potential
      candidates for future studies of allografting under more modern circumstances.
      Some suggestions are made about the introduction of new approaches to treatment.

PMID- 10073564
TI  - High-dose therapy in multiple myeloma and primary amyloidosis: an overview.
AB  - Autologous stem cell transplantation is a reasonable approach for patients
      younger than 70 years and should be discussed with each patient before
      instituting alkylating agent therapy. Ideally, it should be done in a clinical
      trial. Although most patients relapse, it does provide a modest prolongation of
      survival. The major needs are an improved preparative regimen before
      transplantation and the removal of myeloma cells and, more importantly, their
      precursors from the peripheral blood. Conventional allogeneic transplantation is
      associated with too high a mortality rate at present and cannot be recommended.
      Efforts must be directed toward reducing transplant-related mortality by T-cell
      depletion or other means. The preparative regimen must be improved, because most
      patients relapse after transplantation. The use of dendritic cells and vaccines
      is an important area of research. The role of autologous transplantation in
      primary amyloidosis (AL) is indeterminate at present. Longer follow-up evaluation
      of patients who have undergone transplantation is needed. Patient selection is a
      critical aspect. Stem-cell transplantation should be performed in a clinical
      trial for primary AL.

PMID- 10073565
TI  - High-dose therapy and transplantation in non-Hodgkin's lymphoma.
AB  - High-dose therapy and transplantation have been explored as a therapeutic option
      for patients with non-Hodgkin's lymphomas (NHLs) for the past two decades, in an
      effort to improve the long-term outcome of this spectrum of disorders. Although a
      plethora of pilot and phase II studies in the various subtypes of NHL have been
      reported, there is a problematic lack of randomized phase III trials that would
      aid in answering important questions regarding the role of transplantation in
      these disease processes. The results of transplantation trials for these patients
      are also confounded by the relatively short follow-up intervals in low-grade NHL
      and small patient numbers in studies of transplantation for less common NHL
      subtypes, such as lymphoblastic, Burkitt's, and mantle cell lymphomas. The
      emerging late toxicities of transplantation are of increasing concern and
      underscore the need for more studies that address questions of relative
      therapeutic benefits. Fortunately, the limitations of these existing studies are
      recognized, and new transplantation trials presently underway or in development
      are beginning to address these concerns. As clinical transplantation moves into a
      more mature phase, these phase III studies should provide more definitive answers
      as to the specific role of transplantation in specific subtypes of NHL.

PMID- 10073566
TI  - High-dose chemotherapy in ovarian carcinoma.
AB  - High-dose chemotherapy supported by bone marrow transplantation is being
      seriously investigated as a way to increase response and prolong survival in
      women with ovarian carcinoma. This report is a broad review of attempts over the
      past several years to demonstrate advantages of the high-dose approach. The
      existing data for dose escalation, short of doses requiring hematopoietic stem
      cell transplant, demonstrate increased response rates, but no survival advantage.
      When even higher doses of chemotherapy are used in concert with autologous
      transplant to combat hematologic toxicities, even higher response rates have been
      reported. Despite this, all survival data from these later studies are limited.
      There is some hint of survival benefit in certain populations, such as those
      women with limited disease or perhaps in more advanced disease that has not been
      previously treated. All of the studies taken as a whole effectively demonstrate
      the need for randomized trials to address the issue of whether this approach
      provides any advantage over standard-dose chemotherapy. Future efforts at
      studying high-dose chemotherapy and autologous transplantation for ovarian
      carcinoma should be focused in this area; until results are available from such
      trials, high-dose chemotherapy with transplant will remain an experimental
      procedure.

PMID- 10073567
TI  - High-dose chemotherapy with autologous stem-cell support for germ cell tumors: a
      critical review.
AB  - High-dose chemotherapy (HDC) with autologous stem-cell support (ASCS) has been
      investigated in patients with cisplatin-resistant, relapsed, or poor-prognosis
      germ cell tumor (GCT). Although some of these patients have benefited from this
      approach, it is unknown when best to administer such therapy. This review
      categorizes the HDC/ASCS trials into those performed as (1) salvage therapy for
      second or greater relapse, (2) salvage therapy for first relapse, and (3) first
      line therapy. From the trials performed to date, earlier use of HDC/ASCS (first
      line or salvage therapy in first relapse) achieved a higher durable remission
      rate than when used later as salvage therapy in second or greater relapse
      (approximately 50% v 15%, respectively). HDC/ASCS is not beneficial for relapsed
      or cisplatin-resistant primary extragonadal GCT patients, but may have a role in
      testicular GCT who are not "absolutely" cisplatin-resistant. Trial differences
      regarding the patients selected and the high-dose transplant preparative regimen
      used have made precise comparative analyses difficult. There has been only one
      phase III trial and it did not show a survival advantage to the HDC/ASCS arm,
      although this trial had significant methodological difficulties. In the future,
      more definitive treatment recommendations may be made upon completion of two
      ongoing phase III trials comparing HDC/ASCS with standard chemotherapy in the
      first salvage and front-line settings.

PMID- 10073568
TI  - High-dose chemotherapy in adult sarcomas: no standard yet.
AB  - The management of patients with sarcoma involves a multidisciplinary approach,
      with surgery, radiotherapy, and chemotherapy all playing their part. The role of
      high-dose chemotherapy in this heterogeneous and rare disease remains
      controversial and unproven. Adult soft tissue sarcomas (STS) generally are poorly
      responsive to standard chemotherapy, with doxorubicin (DOX) and ifosfamide (IFOS)
      being the only available agents showing response rates of greater than 20%.
      Combination regimens generally do not add efficacy, but do add toxicity. For both
      active agents, a dose-response relationship has been shown. Therefore, and in the
      absence of new and better drugs or schedules, dose-intensifying and even high
      dose chemotherapy regimens (HDCT) with cellular support have been studied.
      Unfortunately, most of these trials were noncontrolled, studying heterogeneous
      patient groups. Furthermore, these strategies never resulted in a significantly
      longer overall survival (OS), and therefore remain highly investigational.
      Primarily, the search for new active drugs should be encouraged. Although HDCT
      cannot be considered common practice in STS, the role of this strategy as
      consolidation therapy in well-defined subsets of patients, using prognostic
      factors, could be explored further in carefully designed studies. The Ewing tumor
      family (ET), as a distinct entity, is more responsive to chemotherapy and
      considered a systemic disease. Results from small, noncontrolled studies indicate
      that consolidation therapy by megatherapy and hematologic support contributes to
      an improved outcome in "high-risk" Ewing patients compared with historical
      controls. However, the exact role of HDCT remains to be determined in properly
      designed randomized studies with well-defined patient groups and appropriate
      sample sizes. The collaboration between cooperative groups in the design and
      execution of randomized studies with appropriate sample sizes should be
      encouraged. This approach might provide us with essential answers enabling
      further progress. In addition, each sarcoma patient should, as much as possible,
      be treated within the context of a properly designed study.

PMID- 10073569
TI  - Macromolecular and ultrastructural organization of the mitotic chromosome
      scaffold.
AB  - Using electron microscopy (EM), we have examined three structural domains of the
      mitotic chromosome scaffold of mouse erythroleukemia (MEL) Friend cells with
      different morphologic organization: centromeric, intermediate, and telomeric. The
      intermediate, most extensive, domain exhibited a specific fibrogranular structure
      representing tightly packed granular bodies with diameters between 20 and 60 nm.
      The chromosome scaffold contained three main components: proteins (81%), RNA
      (12%), and DNA (7%). The residual DNA extracted from the scaffold represented
      short fragments, 300 bp on average, belonging to the class of tandemly arranged
      repetitive DNA. In situ hybridization experiments confirmed its typical
      centromeric location. Scaffold RNA represented three fractions: a major RNA
      fraction with an electrophoretic mobility corresponding to that of 5S RNA and two
      minor fractions with electrophoretic mobilities somewhat lower than that of 18S
      RNA. Scaffold RNA was localized mainly in the centromeric region. We show that
      the newly synthesized protein component of the chromosome scaffolds migrates
      slowly to the chromosomes, reaching a maximum specific radioactivity 12 h from
      the onset of the chase period.

PMID- 10073570
TI  - A bifunctional regulatory element of the human ApoA-I gene responsive to a distal
      enhancer.
AB  - Promoter elements located up to 2 kb upstream of the apolipoprotein A-I (apoA-I)
      gene are necessary for apoA-I expression in liver and intestine cells in tissue
      culture. In transgenic mice, a distal enhancer located between the apoA-IV and
      apoC-III genes is additionally necessary for tissue-specific expression of apoA-I
      in liver and intestine. We have identified a previously uncharacterized
      regulatory element between 746 and 856 nucleotides 5' of the apoA-I transcription
      start site that differentially affects the expression of apoA-I reporter plasmids
      in intestine cells dependent on the presence of the distal apolipoprotein
      enhancer. Deletion of the -856/-746 sequence strongly repressed transcription in
      the presence of the apolipoprotein enhancer, but in the absence of the enhancer,
      deletion of the -856/-746 element increased transcription. By contrast, in liver
      cells, deletion of the -856/-746 element strongly repressed transcription in the
      presence of the distal enhancer but had no detectable effect on transcription in
      the absence of the distal enhancer. Electrophoretic mobility shift analysis
      revealed tissue-specific and sequence-specific protein-DNA complexes formed by
      the -856/-746 element in intestine, liver, and HeLa cell nuclear extracts. The
      complexes formed by extracts of intestinal cells differed from those of liver and
      HeLa cells by their sensitivity to DNase digestion and their pattern of protein
      footprints. Collectively, the data suggest that the -856/-746 sequence is a
      composite regulatory element that interacts with multiple proteins and the
      apolipoprotein distal enhancer to achieve tissue-specific expression of apoA-I.

PMID- 10073571
TI  - Cloning and expression of Aplysia carboxypeptidase D, a candidate prohormone
      processing enzyme.
AB  - Many peptide hormones in a variety of species are produced from larger precursors
      by limited proteolysis at basic amino acid-containing sites. The marine mollusc
      Aplysia has homologs of mammalian peptide-processing enzymes, including furin,
      prohormone convertase 1 (PC1), PC2, and carboxypeptidase E (CPE). A novel
      neuronal Aplysia enzyme was recently identified that was most closely related to
      carboxypeptidase D (CPD; Fan and Nagle, DNA Cell Biol. 15, 937-945, 1996), a
      second carboxypeptidase thought to be present in the secretory pathway and to
      contribute to peptide hormone processing. We have identified and cloned multiple
      overlapping bag-cell neuron cDNAs that encode two proteins that are members of
      the CPD family. Sequence analyses demonstrate that the longer CPD protein (1446
      residues) contains an N-terminal signal peptide and four carboxypeptidase-like
      domains; the third and fourth domains are not predicted to form active enzymes,
      as several critical residues are absent. The shorter CPD protein is predicted to
      contain two active carboxypeptidase-like domains. Northern blot analysis
      identified a major Aplysia CPD mRNA (5.3 kb) and several smaller minor
      transcripts in central nervous system tissue. The CPD was purified from Aplysia
      ovotestis using a method previously developed for mammalian CPD. The purified
      Aplysia CPD binds antisera raised against regions of the protein encoded by the
      Aplysia cDNA clone, as well as an antiserum raised against duck CPD. The
      enzymatic properties of purified Aplysia CPD are generally similar to those of
      mammalian CPD. Aplysia CPD is a candidate prohormone-processing enzyme that may
      play a role in the processing of Aplysia prohormones in the secretory pathway.

PMID- 10073572
TI  - In yeast, upc2-1 confers a decrease in tolerance to LiCl and NaCl, which can be
      suppressed by the P-type ATPase encoded by ENA2.
AB  - Wild-type yeast cells are unable to take up sterols from their growth media under
      aerobic conditions and are relatively resistant to monovalent cations. A yeast
      mutant (upc2-1) with a defect in the aerobic exclusion of sterols was found to
      have increased sensitivity to LiCl and NaCl. Although cation sensitivity has been
      reported for mutants that synthesize altered sterols, the mutant with upc2-1
      continues to produce the normal sterol, ergosterol. The ENA2 gene was cloned on
      the basis of remediating the hypersensitivity to the monovalent cations.

PMID- 10073573
TI  - Characterization of the sequence and expression of a Ykt6 prenylated SNARE from
      rat.
AB  - The Ykt6 protein represents a novel soluble N-ethylmaleimide-sensitive fusion
      protein receptor (SNARE), as it is the only one known without a hydrophobic
      transmembrane region at the carboxy terminus. For this SNARE, however, membrane
      interaction is thought to be mediated through a
      cysteine/aliphatic/aliphatic/methionine or histidine (CAAX) C-terminal motif, a
      consensus sequence involved in prenylated membrane anchoring. To date, two full
      length Ykt6 cDNAs have been reported, these being in yeast and human, with a
      further protein predicted from a Caenorhabditis elegans cosmid. Using a mouse EST
      clone identified as having 65% homology with the human Ykt6, we isolated a cDNA
      clone encoding the rat Ykt6 homolog (rYkt6). Sequence analysis of rYkt6
      demonstrated that a high level of species conservation exists between the rat and
      human prenylated SNAREs, as both the nucleotide and amino acid sequences share
      >90% homology. Mammalian Ykt6 is shown here for the first time to be
      constitutively expressed in a variety of tissues. The species conservation and
      ubiquitous expression of prenylated SNAREs hence may be indicative of an
      important and central role for these proteins in cellular protein trafficking.

PMID- 10073574
TI  - Multiple promoter elements including a novel repressor site modulate expression
      of the chick ovalbumin gene.
AB  - As is the case with many eukaryotic genes, regulation of the chick ovalbumin (Ov)
      gene involves both positive and negative modulation. Recent studies indicate that
      positive regulation by steroids entails binding of several proteins to a hormone
      response unit called the steroid-dependent regulatory element (SDRE; -892 to 
      780). In addition, gene activity is suppressed by factor(s) acting through the
      negative regulatory element (NRE; -308 to -88). Previous data suggested that the
      NRE is composed of multiple, independently acting negative elements. The goal of
      the present studies was to define more precisely the locations of these negative
      elements and to investigate their functional interactions. Transfection analyses
      of linker scanning mutants revealed a strong repressor site, designated the COUP
      adjacent repressor (CAR) site, located between -119 and -111. Gel mobility shift
      analyses with the CAR element suggested that it may play a role in the
      developmental regulation of the Ov gene. A weaker repressor element was also
      identified at about -275. Surprisingly, two positive sites were found, one of
      which is the binding site for the estrogen-responsive transcription factor delta
      EF1. These results demonstrate that the Ov NRE contains not only sites
      responsible for the repression of the gene but also a positive element that is
      required for responsiveness to steroid hormones.

PMID- 10073575
TI  - Hepatocyte nuclear factor 3 (winged helix domain) activates trefoil factor gene
      TFF1 through a binding motif adjacent to the TATAA box.
AB  - The winged helix transcription factors HNF-3/FKH (forkhead homologs) activate
      endodermal-derived and acute-phase gene expression and control gut development in
      Drosophila. Trefoil factor family (TFFs) peptides are vertebrate products
      secreted by mucin-producing epithelial cells of the gastrointestinal tract
      involved in restitution and repair of the mucosa. They are positively regulated
      in ulcerative and neoplastic conditions. We describe a consensus sequence in
      human and rodent TFF promoters close to the TATAA box showing striking similarity
      to the binding site of the HNF-3/FKH family. In gel retardation assays, HNF-3
      alpha and beta bound predominantly to the site in TFF1 (formerly pS2) and, to a
      lesser extent, to the sites in TFF2 or TFF3. Mutations generated in this motif
      severely impaired transcription of TFF1 reporter genes. Cotransfection with
      expression vectors of HNF-3alpha and beta, but not the related HFH 11A and B,
      specifically activated the wild-type TFF1 reporter genes. Activation of
      endogenous expression of TFF1 by HNF-3 alpha and beta gene products was more than
      1000 fold in the pancreatic cell line Capan-2 and fivefold in the gastric cell
      line MKN-45, whereas the intestinal cell lines HUTU 80 and HT-29 displayed no
      effect. Thus, HNF-3/FKH factors contribute causally to cell-specific regulation
      of TFF genes and may explain the acute-phase response of TFF peptides.

PMID- 10073576
TI  - Enhanced binding of HLF/DBP heterodimers represents one mechanism of PAR protein
      transactivation of the factor VIII and factor IX genes.
AB  - The regulatory regions of the genes for coagulation Factors VIII and IX contain
      binding sites for both liver-enriched and ubiquitous transcriptional regulators.
      We investigated the role of the liver-enriched protein, hepatic leukemia factor
      (HLF), in mediating transcriptional regulation of the Factor VIII and IX genes.
      Using transient transfection assays in HepG2 hepatoma cells, we demonstrated the
      ability of HLF alone and in synergistic combination with the D-box binding
      protein (DBP), another proline and acidic-rich (PAR) protein family member, to
      transactivate these promoters. HLF is capable of binding to multiple sites in
      both the Factor VIII and Factor IX promoters. At least some of the synergistic
      activation of the Factor VIII promoter seen with HLF and DBP cotransfection can
      be attributed to increased binding of HLF-DBP heterodimers to two Factor VIII
      promoter sites. We have also demonstrated that an E2A-HLF chimera, derived from a
      t(17;19) translocation in pre-B acute lymphoblastic leukemia (ALL) cells, is
      capable of mediating expression from the Factor VIII and Factor IX promoters in
      both hepatoma cells and pre-B ALL cells. These observations indicate that the PAR
      family of transcription factors plays an important and complex role in regulating
      expression of the Factor VIII and Factor IX genes, involving the binding of both
      homodimeric and heterodimeric complexes of HLF and DBP to several sites in the
      promoters. Finally, these studies reaffirm the potential role of dimeric
      transcription factor complexes in mediating interactions with specific promoter
      elements, which, in the case of the Factor VIII promoter, results in dramatically
      enhanced binding of HLF-DBP heterodimers to two cis-acting sequences. These
      observations further our understanding of the role played by members of the PAR
      family of transcription factors in regulating expression of the Factor VIII and
      Factor IX genes.

PMID- 10073577
TI  - Identification of mouse CPX-1, a novel member of the metallocarboxypeptidase gene
      family with highest similarity to CPX-2.
AB  - The recent finding that Cpe(fat)/Cpe(fat) mice, which lack carboxypeptidase E
      (CPE) activity because of a point mutation, are still capable of a reduced amount
      of neuroendocrine peptide processing suggested that additional carboxypeptidases
      (CPs) participate in this processing reaction. Searches for novel members of the
      CPE gene family led to the discovery of CPD, CPZ, AEBP1, and CPX-2. In the
      present report, we describe mouse CPX-1, another novel member of this gene
      family. Like AEBP1 and CPX-2, CPX-1 contains an N-terminal region of 160 amino
      acids with sequence similarity to the discoidin domain of a variety of proteins.
      The 410-residue CP-like domain of CPX-1 has 54% to 62% amino acid sequence
      identity with AEBP1 and CPX-2 and 33% to 49% amino acid identity with other
      members of the CPE subfamily. However, several active-site residues that are
      important for catalytic activity of other CPs are not conserved in CPX-1.
      Furthermore, CPX-1 expressed in either the baculovirus system or the mouse AtT-20
      cell line does not cleave standard CP substrates. Northern blot analysis showed
      the highest levels of CPX-1 mRNA in testis and spleen and lower levels in
      salivary gland, brain, heart, lung, and kidney. In situ hybridization of CPX-1
      mRNA in embryonic and fetal mouse tissue showed expression throughout the head
      and thorax, with abundance in primordial cartilage and skeletal structures. In
      the head, high levels of CPX-1 mRNA were associated with the nasal mesenchyme,
      primordial cartilage structures in the ear, and the meninges. In the thorax, CPX
      1 mRNA was expressed in multiple developing skeletal structures, including
      chondrocytes and perichondrial cells of the rib, vertebral, and long-bone
      primordia. Taken together, these findings suggest that it is unlikely that CPX-1
      functions in the processing of neuroendocrine peptides. Instead, CPX-1 may have a
      role in development, possibly mediating cell interactions via its discoidin
      domain.

PMID- 10073578
TI  - Arthritis: is the cure in your genes?

PMID- 10073579
TI  - Measurement of intracompartmental pressure with use of a new electronic
      transducer-tipped catheter system.
AB  - Laboratory and clinical tests were carried out to determine the clinical
      usefulness, validity, and safety of a new self-calibrating, battery-powered
      monitoring system for the measurement of intramuscular pressure with use of an
      electronic transducer-tipped catheter. The eight probes accurately recorded
      applied pressures ranging from zero to 160 millimeters of mercury (zero to 21.33
      kilopascals). The system registered little temperature-induced drift (maximum,
      1.25 millimeters of mercury [0.17 kilopascal]) between dry room temperature and
      40 degrees Celsius. There were also minimum variations (range, -0.14 to 0.81
      millimeter of mercury [0.02 to 0.11 kilopascal]) in the pressures recorded during
      a twenty-four-hour period. The resting pressure in the tibialis anterior muscle
      of twenty volunteers who had normal limbs was a mean (and standard deviation) of
      13.1+/-8.3 millimeters of mercury (1.75+/-1.11 kilopascals). There was a good
      correlation between externally applied pressures (zero, twenty, forty, sixty,
      eighty, and 100 millimeters of mercury [zero, 2.67, 5.33, 8.00, 10.66, and 13.33
      kilopascals] applied with use of antishock trousers) and the pressures measured
      in the tibialis anterior muscle of four volunteers (r = 0.997 to 0.999). The
      injection of sterile saline solution into the tibialis anterior muscle of a
      volunteer and the use of high-frequency recording during muscular activity showed
      a high degree of responsiveness and sensitivity to changes in intramuscular
      pressure. We also prospectively evaluated the clinical usefulness of the system
      and found it to be easy to assemble, calibrate, and use. Thus, this reusable,
      electronic transducer-tipped catheter system, which is based on a noninfusion
      technique, is simple, minimally traumatic, and highly precise. It is free of
      hydrostatic pressure artifacts and provides dynamic responses to changes in
      intramuscular pressure.

PMID- 10073580
TI  - Injury to the growth plate after Pemberton osteotomy.
AB  - The Pemberton osteotomy involves cutting directly into the iliopubic and
      ilioischial limbs of the triradiate cartilage of the acetabulum. Complete closure
      of the triradiate cartilage after this osteotomy has been described in case
      reports. The present experimental study was performed to determine whether
      physeal osseous bars formed after Pemberton osteotomy. Eight Pemberton
      osteotomies were performed in six piglets. The animals were killed, and the
      acetabula were studied with use of radiography, computed tomography, and
      histological analysis for evidence of physeal injury. Plain anteroposterior
      radiographs of the pelvis did not clearly demonstrate the formation of osseous
      bars. However, Bucholz radiographs, made with the acetabulum placed directly on
      the cassette, showed osseous bars in three of the four specimens that were
      studied in this manner. Histological sections of the eight specimens of
      triradiate cartilage demonstrated five osseous bars in the iliopubic limb and
      four in the ilioischial limb. In two specimens, there was disruption of the
      cartilage without osseous bridging. Only two of the eight specimens had normal
      histological findings in both the iliopubic and the ilioischial limb of the
      triradiate cartilage.

PMID- 10073581
TI  - The functional outcome of operative treatment of ununited fractures of the
      humeral diaphysis in older patients.
AB  - Twenty-two elderly patients (average age, seventy-two years) who had an atrophic,
      unstable, ununited fracture of the humeral diaphysis were managed with plate-and
      screw fixation and application of an autogenous bone graft from the iliac crest.
      Fifteen of the patients had had at least one previous operation in an attempt to
      obtain union of the fracture. One patient had an active infection and two had a
      quiescent infection, all with Staphylococcus epidermidis. The average duration of
      nonunion before the patients were first seen by us was two years and four months
      (range, five months to sixteen years). Fifteen of the nonunions were synovial. In
      each patient, at least one modification of the standard technique of plate-and
      screw fixation was needed as a result of osteopenia. In order to enhance
      fixation, the standard protocol incorporated the use of a long plate (with an
      average of eleven holes and an average length that was 76 percent of that of the
      bone), a plate with a blade (used in thirteen patients), and replacement of
      loose, 4.5-millimeter cortical-bone screws with 6.5-millimeter cancellous-bone
      screws (twelve patients). Spiked nuts (Schuhli nut; Synthes, Paoli, Pennsylvania)
      that lock the screws to the plate, creating a solid point of fixation analogous
      to a blade, were incorporated into the protocol when they became available (used
      in six patients). In five limbs, the nonunion was associated with an osseous
      defect that could not be addressed by shortening of the bone alone. Three of
      these limbs were stabilized with a bridge plate that had been contoured to stand
      away from the bone at the site of nonunion (so-called wave-plate osteosynthesis),
      and the remaining two limbs were stabilized with a combination of intramedullary
      and extramedullary plates. In one of these two limbs, the extramedullary plate
      was contoured (that is, a wave plate). The fracture united in twenty (91 percent)
      of the patients. There was no progressive loosening or breakage of a fixation
      device, even in two patients who had radiographs that were suggestive of an
      incomplete union. Five of the patients were followed for a limited duration
      (average, one year and six months) as a result of death or illness. They had two
      excellent results, two good results, and one poor result according to a
      modification of the rating system of Constant and Murley. The remaining seventeen
      patients, including the two who had a persistent nonunion, were followed for an
      average of three years and one month (range, two years to five years and ten
      months). They had significant improvements in all of the functional scores at the
      most recent follow-up evaluation: the average score according to the modified
      system of Constant and Murley increased from 9 to 72 points (p < 0.001), the
      average score according to the Enforced Social Dependency Scale decreased from 39
      to 9 points (p < 0.001), and the average score based on the Disabilities of the
      Arm, Shoulder, and Hand Questionnaire decreased from 77 to 24 points (p < 0.001).
      According to the scores based on the Disabilities of the Arm, Shoulder, and Hand
      Questionnaire, nine of the seventeen patients who had been followed for more than
      two years had an excellent result, four had a good result, two had a fair result,
      and the two who had a persistent nonunion had a poor result. Complications
      included postoperative delirium, a stitch abscess, transient radial nerve palsy,
      a fracture distal to the plate, and the need for a blood transfusion, in one
      patient each. Two patients had a fibrous union. There were no major medical
      complications. An unstable, united fracture of the humeral diaphysis can be
      extremely disabling and may threaten the ability of an elderly patient to
      function independently. Operative treatment can be very successful when the
      techniques of plate-and-screw fixation are modified to address osteopenia and
      relative or absolute loss of bone. Healing of the fracture substantially improves
      function and the degree of independence

PMID- 10073582
TI  - The effects of melatonin therapy on the development of scoliosis after
      pinealectomy in the chicken.
AB  - The mechanism underlying the development of scoliosis after pinealectomy in young
      chickens is unknown. However, since the main product of the pineal gland is
      melatonin, melatonin remains an obvious focus in studies designed to discover
      this mechanism. One confounding factor is that serum melatonin levels are close
      to zero after pinealectomy but scoliosis does not develop in all chickens that
      have had this procedure. Therefore, the role of melatonin in the development of
      scoliosis in chickens after pinealectomy remains controversial. In the current
      investigation, two pilot studies demonstrated that a physiological therapeutic
      dose of melatonin (2.5 milligrams per kilogram of body weight) restored the
      circadian rhythm of melatonin, as measured by serum assay. In the main study,
      this dose was administered daily starting either immediately after the
      pinealectomy or two weeks after it, when scoliosis had developed. Scoliosis was
      assessed on weekly radiographs, and the Cobb angle was determined for all
      chickens in which scoliosis developed. Overall, scoliosis developed in only 56
      percent (fifty) of the eighty-nine chickens that had had a pinealectomy; this
      rate was consistent throughout all experimental groups. Scoliosis did not develop
      in any of the control chickens, which did not have a pinealectomy. On the basis
      of the average Cobb angles in the chickens in which scoliosis had developed, it
      was determined that neither the prevalence nor the pattern of the scoliosis was
      affected by the therapy in any of the experimental groups. It was thus concluded
      that melatonin therapy after pinealectomy in young chickens has no effect on the
      development or progression of scoliosis. These results raise doubts regarding the
      role of melatonin in the development of scoliosis after pinealectomy in the young
      chicken.

PMID- 10073583
TI  - Survivorship analysis of hips treated with core decompression for nontraumatic
      osteonecrosis of the femoral head.
AB  - We reviewed the long-term results of core decompression for the treatment of
      nontraumatic osteonecrosis of the femoral head, performed in thirty-four patients
      (fifty-four hips) between January 1, 1981, and June 30, 1995. Twenty patients (59
      percent) had bilateral involvement. The mean age of the patients at the time of
      presentation was thirty-eight years (range, twenty-two to eighty-three years).
      The presumed risk factors were use of corticosteroids (thirty-seven hips),
      excessive intake of alcohol (eight hips), and use of adrenocorticotropic hormone
      for the treatment of multiple sclerosis (two hips); the remaining seven hips had
      idiopathic osteonecrosis. According to a modification of the classification
      system of Ficat and Arlet in combination with the system of Steinberg et al.,
      thirteen hips were stage I (normal radiographs) preoperatively; seven, stage IIA
      sclerotic; sixteen, stage IIA cystic or sclerocystic; ten, stage IIB
      (transitional stage, with a crescent sign); and eight, stage III (collapse). The
      mean duration of follow-up after the core decompression was 120 months (range,
      twenty-four to 196 months). The result was considered successful if the patient
      was asymptomatic, with no progression of the disease, and unsuccessful if there
      was radiographic failure (progression to stage III [collapse]) or clinical
      failure (the need for a subsequent operation), or both. The Kaplan-Meier product
      limit method was used to estimate clinical and radiographic survival. Overall,
      twenty-six hips (48 percent) had a satisfactory clinical result and twenty (37
      percent) survived according to radiographic criteria. Radiographic or clinical
      failure, or both, were seen in four of the thirteen stage-I hips, none of the
      seven stage-IIA sclerotic hips, thirteen of the sixteen stage-IIA cystic or
      sclerocystic hips, nine of the ten stage-IIB hips, and all eight stage-III hips.
      On the basis of the Cox proportional-hazards regression model, significant
      predictors of overall failure included an advanced preoperative radiographic
      stage (p < 0.0001), a shorter duration of symptoms (p < 0.05), and use of
      corticosteroids (p < 0.05). No association was found between age, gender,
      excessive intake of alcohol, or renal transplantation and the overall outcome.
      Two patients (two hips; 4 percent) had a postoperative complication. One patient
      had a fracture of the femoral neck, and the other had a hematoma. Our findings
      suggest that core decompression is a safe and effective procedure for the
      treatment of stage-I or stage-IIA sclerotic disease. These data also demonstrate
      the importance of differentiating between stage-IIA sclerotic disease and stage
      IIA cystic or sclerocystic disease. We believe that core decompression has a
      limited role in the operative management of patients who have evidence of cystic
      changes in the femoral head on plain radiographs.

PMID- 10073584
TI  - Clinical and radiographic outcomes of total hip arthroplasty with insertion of an
      anatomically designed femoral component without cement for the treatment of
      primary osteoarthritis. A study with a minimum of six years of follow-up.
AB  - We evaluated the clinical and radiographic outcomes of 100 consecutive primary
      total hip arthroplasties in which a proximally coated anatomically designed
      femoral component was fixed without cement for the treatment of primary
      osteoarthritis. The minimum duration of follow-up was six years (average, 7.1
      years). The eighty-eight patients who had the arthroplasties were followed
      prospectively with a standard clinical evaluation that involved use of the Harris
      hip score and a radiographic evaluation based on the criteria of the Hip Society.
      Bone ingrowth was evaluated with the method of Engh et al. The average age of the
      patients at the time of the operation was 62.6 years (range, thirty-nine to
      eighty-four years). Fifty-one patients were men and thirty-seven were women. The
      average preoperative Harris hip score was 48 points, with an average pain score
      of 15 points and an average function score of 26 points. Nonmechanical
      complications that necessitated a revision operation included one deep
      hematogenous infection, one late periprosthetic fracture, and a 0.5-inch (1.27
      centimeter) limb-length discrepancy. At the time of the most recent follow-up,
      the average Harris hip score was 96 points, with an average pain score of 42
      points and an average function score of 45 points. The prevalence of pain in the
      anterior part of the thigh was 5 percent (five hips). One patient had a revision
      of the femoral component because of aseptic loosening, and one had a revision of
      the acetabular component because of recurrent dislocations. Radiographic
      assessment revealed consistent evidence of proximal bone ingrowth. No complete
      radiolucent line was identified, except around the stem that had loosened. Twenty
      seven femoral components were associated with slight pedestal formation. No
      osteolytic lesion of the femur was identified. Nonprogressive pelvic osteolysis
      was identified in four hips, but none of the lesions were more than two
      millimeters in diameter. None of the acetabular components migrated, and no
      radiolucent line of more than two millimeters in thickness was seen around any
      acetabular cup. The data from this study, in which the minimum duration of follow
      up was six years, indicate that the anatomically designed prosthesis can provide
      good results, with low prevalences of pain in the thigh and loosening of the
      component, in younger, active patients.

PMID- 10073585
TI  - The hemispherical Harris-Galante acetabular cup, inserted without cement. The
      results of an eight to eleven-year follow-up of one hundred and sixty-eight hips.
AB  - We studied the results for 168 available hips from a series of 324 consecutive
      primary total hip arthroplasties that had been performed with insertion of a
      Harris-Galante-I acetabular component without cement. The acetabulum had been
      reamed in a so-called line-to-line manner, and the cup had been fixed with one to
      four screws. A femoral component with a modular alumina-ceramic head had been
      inserted with cement in all hips. The median duration of follow-up was 112 months
      (range, 101 to 131 months). Of the original 324 hips, 109 could not be included
      in the clinical and radiographic follow-up because the patients had died and
      thirty could not be included because the patients were not available for
      examination. Seventeen hips had had a revision of the acetabular cup: five,
      because of infection; five, because of dislocation; three, because of aseptic
      loosening; and four, because of technical failure. This left 168 hips for
      clinical and radiographic follow-up; of these, fifteen had had a revision of the
      femoral component only. Of the remaining 153 hips, which had not had a revision,
      147 (96 percent) were considered by the patient to have a satisfactory, good, or
      excellent result. One hip was found to have a loose cup on radiographic
      evaluation and was therefore considered to have failed, but the clinical function
      was good. We concluded that, with an overall rate of aseptic loosening of 1
      percent (four of 324) after an intermediate (ten-year) duration of follow-up, use
      of this cup has good results.

PMID- 10073586
TI  - Ehlers-Danlos syndrome type VII: clinical features and molecular defects.
AB  - We evaluated the clinical features, molecular defects, and problems associated
      with the management of two patients who had type-VII Ehlers-Danlos syndrome and
      reviewed the cases of eighteen patients with this condition who had been reported
      on previously. The typical clinical features associated with this syndrome
      include bilateral congenital dislocation of the hip; severe generalized
      hypermobility of the joints; multiple dislocations of joints other than the hip;
      muscular hypotonia; and hyperelasticity, fragility, and a doughy texture of the
      skin. Collagen and DNA analyses demonstrated that both of our patients had type
      VIIB Ehlers-Danlos syndrome, which is caused by heterozygous new mutations of the
      COL1A2 gene that encodes the proalpha2(I) chain of type-I procollagen. The
      obligatory GT dinucleotide at the splice donor site of intron 6 was altered in
      both of our patients: one patient (Case 1) had an A substitution of the G
      nucleotide, and the other patient (Case 2) had a C substitution of the T
      nucleotide. Abnormal splicing resulted in the loss of the exon 6-encoded N
      telopeptide, which includes the N-proteinase cleavage site. Despite multiple
      operative procedures, one of our patients, who was thirty-seven years old at the
      time of the most recent follow-up, continued to have persistent subluxation of
      the right hip and osteoarthritis of the left hip. Closed reduction of the
      dislocated hips, regardless of the type of immobilization used, was unsuccessful
      in all twenty patients. The results of open reduction were improved when
      capsulorrhaphy was combined with iliac or femoral osteotomy, or both.

PMID- 10073587
TI  - Superior compressive strength of a calcaneal fracture construct augmented with
      remodelable cancellous bone cement.
AB  - Twenty-six paired, fresh-frozen cadaveric feet were disarticulated at the ankle
      joint, and the dome of the talus was potted. Stress-risers were placed along the
      medial, lateral, and posterior aspects of the calcaneus, and the specimen was
      loaded rapidly to failure in a testing machine to produce a type-IIB displaced
      intra-articular fracture according to the classification system of Sanders et al.
      One specimen of each pair was treated with standard internal fixation with bone
      grafting (the control group), and the other was treated with similar fixation but
      with SRS (Skeletal Repair System) calcium phosphate bone cement placed in any
      osseous defect. All of the specimens were cured for twenty-four hours in a bath
      of saline solution at 37 degrees Celsius. The specimens were tested cyclically
      for ten cycles from zero to 100 newtons at one hertz and for 1010 cycles from
      zero to 350 newtons at one hertz. The deformation per cycle (millimeters per
      cycle), first-cycle deformation (millimeters), number of cycles to failure, and
      number of specimens withstanding the cyclical testing were calculated. The
      specimens were examined radiographically before and after fracture and after
      reconstruction and testing. A large difference in the results of the cyclical
      testing was noted. The specimens that had been augmented with the SRS bone cement
      had an average deformation of 0.00195 millimeter per cycle compared with 1.013
      millimeters per cycle in the control group (p < 0.005). A similar magnitude of
      difference was noted when the results were stratified for good and poor-quality
      bone. Visual examination and radiographs demonstrated that a type-IIB displaced
      intra-articular fracture had been created reproducibly, and computed tomographic
      scans showed that nearly anatomical reconstruction had been achieved in all of
      the specimens. The computerized tomographic scans revealed good filling of the
      osseous voids and no evidence of failure of the cement after cyclical loading.

PMID- 10073588
TI  - Primary hybrid total hip replacement, performed with insertion of the acetabular
      component without cement and a precoat femoral component with cement. An average
      ten-year follow-up study.
AB  - One hundred and twenty-one primary hybrid total hip replacements were performed
      in 107 patients. A titanium, porous-coated, hemispherical acetabular component
      was fixed with screws, and a collared, chromium-cobalt femoral stem, with a
      roughened surface and a thin layer of methylmethacrylate on the proximal third,
      was inserted with contemporary cementing techniques (that is, use of a femoral
      medullary plug, a cement gun, and centrifugation and pressurization of the
      cement). Fifteen patients (fifteen hips) died before a minimum duration of follow
      up of seven years, four patients (four hips) were too ill for a detailed follow
      up examination at the time of the study, and two patients (two hips) refused to
      be evaluated at the time of the latest follow-up. None of these twenty-one hips
      had had a revision or a reoperation at the time of the latest follow-up. Eighty
      six patients (100 hips) were available for clinical follow-up at an average of
      120 months (range, eighty-four to 153 months) and for radiographic follow-up at
      an average of 118 months (range, eighty-four to 153 months). The average age of
      the patients at the time of the index arthroplasty was sixty-five years (range,
      forty-five to eighty-seven years). Three acetabular components were revised
      because of dissociation of the liner in association with a fracture of a locking
      tine. One well fixed acetabular component was revised because of pelvic
      osteolysis, and the femoral stem in the same patient was revised because of
      aseptic loosening. None of the ninety-six remaining acetabular components
      migrated, was classified as radiographically loose, or was revised because of
      aseptic loosening. Osteolytic lesions were identified adjacent to five acetabular
      components, and one of them was treated with bone-grafting around the well fixed
      acetabular shell. Two hips had a continuous radiolucent line at the interface
      between the acetabular implant and the bone. Three femoral stems had evidence of
      radiographic debonding (a radiolucent line that was one millimeter wide or less
      between the cement and the prosthesis), and they were classified as
      radiographically loose despite excellent clinical results. Seven hips had
      osteolytic areas located in the proximal aspect of the most proximal zones of
      Gruen et al., and five had small osteolytic regions in more distal areas. The
      Harris hip score for the eighty-two patients (ninety-six hips) who did not have a
      revision improved from 48 points (range, 22 to 70 points) preoperatively to 92
      points (range, 53 to 100 points) at the most recent follow-up examination. Eighty
      one patients had no, slight, or mild pain in the hip, and they were satisfied
      with the clinical result. In the present study, the hybrid total hip replacement
      with use of the Harris-Galante acetabular component and the Precoat femoral stem
      continued to provide an excellent result for most patients at an average of
      approximately ten years after the operation.

PMID- 10073589
TI  - Posttraumatic cleidoscapular synostosis following a fracture of the clavicle. A
      case report.

PMID- 10073590
TI  - Tendinosis of the elbow (tennis elbow). Clinical features and findings of
      histological, immunohistochemical, and electron microscopy studies.

PMID- 10073591
TI  - The value of recertification to orthopaedic surgery and to the public.

PMID- 10073592
TI  - Neer hemiarthroplasty and Neer total shoulder arthroplasty in patients fifty
      years old or less. Long-term results.

PMID- 10073593
TI  - Ganglioside GM2-activator protein and vesicular transport in collecting duct
      intercalated cells.
AB  - This study describes the molecular characterization of an antigen defined by an
      autoantibody from a woman with habitual abortion as GM2-activator protein. The
      patient showed no disorder of renal function. Accidentally with routine serum
      screening for autoantibodies, an immunoreactivity was found in kidney collecting
      duct intercalated cells. Three distinct patterns of immunostaining of
      intercalated cells were observed: staining of the apical pole, basolateral pole,
      and diffuse cytoplasmic labeling. Ultrastructurally, the immunoreactivity was
      associated with "studs," which represent the cytoplasmic domain of the vacuolar
      proton pump in intercalated cells. This pump is subjected to a shuttling
      mechanism from cytoplasmic stores to the cell membrane, which exclusively occurs
      in intercalated cells. Peptide sequences of a 23-kD protein purified from rat
      kidney cortex showed complete identity with corresponding sequences of GM2
      activator protein. In the brain, GM2-activator protein is required for
      hexosaminidase A to split a sugar from ganglioside GM2. Because neither
      ganglioside GM2 nor GM1 (its precursor) is present in significant amounts in the
      kidney, the previous finding that this tissue contains the highest level of
      activator protein in the body was confusing. In this study, a novel role for GM2
      activator protein in intercalated cells is proposed, and possible roles in the
      shuttling mechanism are discussed.

PMID- 10073594
TI  - Osteopontin expression in fetal and mature human kidney.
AB  - Osteopontin is a secreted phosphoprotein that is expressed by normal kidney, and
      has been associated with a number of functions including cell adhesion,
      migration, signaling, and biomineralization. Although there is a vast literature
      detailing osteopontin localization in various rodent models of both development
      and disease, this article presents the first comprehensive description of
      osteopontin localization in human kidney. In this study, immunohistochemistry,
      immunoelectron microscopy, in situ hybridization, and Northern blotting are used
      to analyze osteopontin protein and mRNA expression in human fetal and normal
      mature renal tissue. Osteopontin is expressed in the human embryonic renal
      tubular epithelium beginning on approximately day 75 to 80 of gestation. In the
      fetal kidney, osteopontin can also be seen occasionally expressed in the ureteric
      buds and in some interstitial cells. As localized at the protein and mRNA level,
      the tubular expression of osteopontin increases with increasing gestational age
      and persists into adulthood. In the normal adult kidney, osteopontin is localized
      primarily to the distal nephron and is strongly expressed by the thick ascending
      limb of the loops of Henle. Osteopontin expression can also be observed in some
      collecting duct epithelium. In cases that exhibit foci of interstitial fibrosis
      and an associated influx of interstitial macrophages, osteopontin expression is
      significantly upregulated in all tubular segments, including proximal tubules.

PMID- 10073595
TI  - Dietary magnesium, not calcium, regulates renal thiazide receptor.
AB  - This study reports for the first time a relationship between dietary Mg and the
      renal thiazide-sensitive Na-Cl cotransporter (TZR, measured by saturation binding
      with 3H-metolazone). Ion-selective electrodes measured plasma ionized magnesium
      (PMg++), calcium (PCa++), and potassium (PK+). Restricting dietary Mg for 1 wk
      decreased PMg++ 18%, TZR 25%, and renal excretion of magnesium (UMg) and calcium
      (UCa) more than 50% without changing PCa++, PK+, or plasma aldosterone. A low Mg
      diet for 1 d significantly decreased PMg++, TZR, UMg and UCa. Return of dietary
      Mg after 5 d of Mg restriction restored PMg++ and TZR toward normal. In the
      control, Mg-deficient, and Mg-repleting animals, TZR correlated with PMg++ (r =
      0.86) and with UMg (r = 0.87) but not UCa (r = 0.09). Increasing oral intake of
      Mg for 1 wk increased PMg++ 14%, TZR 32%, UMg 74%, and UCa more than fourfold
      without changing PCa++ or PK+. In contrast, increasing dietary Ca content from
      0.02% to 1.91% did not change TZR, but increased UCa fivefold without changing
      PCa++. Hormonal mediators (if any) involved in the relationship between dietary
      Mg and TZR remain to be elucidated, as does the relationship between TZR and
      tubular reabsorption of Mg.

PMID- 10073596
TI  - Immunohistochemical localization of multispecific renal organic anion transporter
      1 in rat kidney.
AB  - Renal proximal convoluted tubules have an important role, i.e., to excrete
      organic anions, including numerous drugs and endogenous substances. Recently,
      multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In
      this study, the cellular and subcellular localization of OAT1 in rat kidney was
      investigated. Kidneys from normal rats were perfused and fixed with periodate
      lysine-paraformaldehyde solution and were then processed for immunohistochemical
      analysis using the labeled streptavidin-biotin method, preembedding horseradish
      peroxidase method, and immunogold method. Light microscopic examination revealed
      immunostaining for OAT1 in the middle portion of the proximal tubule (S2
      segment), but not in the initial portion of the proximal convoluted tubule, next
      to the glomerulus. Nephron segments other than the S2 segment and the renal
      vasculature were not stained with antibody to OAT1. Electron-microscopic
      observation using a preembedding method revealed that OAT1 was exclusively
      expressed in the basolateral membrane of S2 segments of proximal tubules. The
      immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles,
      suggesting that OAT1 may not move together with organic anions into the cells.
      These results are consistent with previous physiologic data showing that organic
      anions, including para-aminohippurate, are taken up by the basolateral Na+
      independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In
      conclusion, OAT1 was localized to the basolateral membrane of S2 segments of
      proximal tubules in rat kidneys.

PMID- 10073597
TI  - cGMP-dependent and -independent inhibition of a K+ conductance by natriuretic
      peptides: molecular and functional studies in human proximal tubule cells.
AB  - In immortalized human kidney epithelial (IHKE-1) cells derived from proximal
      tubules, two natriuretic peptide receptors (NPR) were identified. In addition to
      NPR-A, which is bound by atrial natriuretic peptide (ANP), brain natriuretic
      peptide (BNP), and urodilatin (URO), a novel form of NPR-B that might be bound by
      C-type natriuretic peptide (CNP) was identified using PCR. This novel splice
      variant of NPR-B (NPR-Bi) was also found in human kidney. Whereas ANP, BNP, and
      URO increased intracellular cGMP levels in IHKE-1 cells in a concentration
      dependent manner, CNP had no effect on cGMP levels. To determine the physiologic
      responses to these agonists in IHKE-1 cells, the membrane voltage (Vm) was
      monitored using the slow whole-cell patch-clamp technique. ANP (10 nM), BNP (10
      nM), and URO (16 nM) depolarized these cells by 3 to 4 mV (n = 47, 7, and 16,
      respectively), an effect that could be mimicked by 0.1 mM 8-Br-cGMP (n = 15). The
      effects of ANP and 8-Br-cGMP were not additive (n = 4). CNP (10 nM) also
      depolarized these cells, by 3+/-1 mV (n = 28), despite the absence of an increase
      in cellular cGMP levels, indicating a cGMP-independent mechanism. In the presence
      of CNP, 8-Br-cGMP further depolarized Vm significantly, by 1.6+/-0.3 mV (n = 5).
      The depolarizations by ANP were completely abolished in the presence of Ba2+ (1
      mM, n = 4) and thus can be related to inhibition of a K+ conductance in the
      luminal membrane of IHKE-1 cells. The depolarizations attributable to CNP were
      completely blocked when genistein (10 microM, n = 6), an inhibitor of tyrosine
      kinases, was present. These findings indicate that natriuretic peptides regulate
      electrogenic transport processes via cGMP-dependent and -independent pathways
      that influence the Vm of IHKE-1 cells.

PMID- 10073598
TI  - Angiotensin II-stimulated nitric oxide release from porcine pulmonary endothelium
      is mediated by angiotensin IV.
AB  - In this study, a nitric oxide (NO) sensor was used to examine the ability of
      angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from
      porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to
      explore the mechanism of the AngII-stimulated NO release. Physiologic
      concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In
      contrast, Bk, but not AngII, stimulated NO release from PAE cells. AngIII
      stimulated NO release from PPAE cells required extracellular L-arginine and was
      inhibited by L-nitro-arginine methyl ester. AT1 and AT2 receptor inhibition had
      no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV,
      an AngII metabolite with binding sites that are pharmacologically distinct from
      the classic AngII receptors, stimulated considerably greater NO release and
      greater endothelial-type constitutive NOS activity than the same amount of AngII.
      The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV
      mediated NO release as well as NOS activation. The results demonstrate that AngIV
      and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO
      release and the associated endothelium-dependent vasorelaxation. Furthermore,
      these results suggest that differences exist in both AngII- and Bk-mediated NO
      release between PPAE and PAE cells, which may reflect important differences in
      response to these hormones between vascular beds.

PMID- 10073599
TI  - P2 purinoceptor saturation by adenosine triphosphate impairs renal autoregulation
      in dogs.
AB  - Recent studies have suggested a role for P2 purinoceptors on vascular smooth
      muscle cells in the mechanism of renal autoregulation. Experiments were performed
      in anesthetized dogs (n = 9) to examine renal blood flow (RBF) autoregulatory
      efficiency before and after saturation of P2 purinoceptors with acute intra
      arterial administration of ATP (1 mg/kg per min). Dogs were pretreated with the
      nitric oxide synthase inhibitor nitro-L-arginine (NLA) (50 microg/kg per min), to
      avoid endothelial P2 receptor-mediated effects on nitric oxide release caused by
      the intra-arterial ATP infusions. NLA treatment decreased RBF (5.3+/-0.3 to 3.6+/
      0.2 ml/min per g) and sodium excretion (3.6+/-0.4 to 0.9+/-0.2 ml/min per g)
      without producing significant changes in GFR (0.92+/-0.04 to 0.90+/-0.06 ml/min
      per g) or RBF autoregulatory efficiency. ATP administration to NLA-treated dogs
      resulted in further decreases in RBF (2.8+/-0.2 ml/min per g), GFR (0.58+/-0.05
      ml/min per g), and sodium excretion (0.6+/-0.2 micromol/min per g). In addition,
      there was marked impairment of RBF autoregulatory efficiency during ATP infusion.
      The slopes of the arterial pressure-blood flow relationships at renal arterial
      pressures of >75 mmHg were significantly altered, from 0.003+/-0.001 to 0.2+/
      0.002 ml/min per g per mmHg. Discontinuation of ATP infusion restored RBF
      autoregulatory efficiency. Norepinephrine (5 microg/kg per min) administration in
      these NLA-treated dogs decreased RBF (2.5+/-0.3 ml/min per g; n = 4) to a similar
      extent, compared with ATP, but did not impair RBF autoregulation. These results
      support the hypothesis that P2 purinoceptors may be involved in mediating
      autoregulatory adjustments in renal vascular resistance.

PMID- 10073600
TI  - Prominence of cell-mediated immunity effectors in "pauci-immune"
      glomerulonephritis.
AB  - The majority of patients with rapidly progressive crescentic glomerulonephritis
      show histologic features of extensive necrosis and focal and segmental
      proliferation with fibrin production, but little or absent Ig deposition in the
      glomerulus. This subcategory of the disease, labeled "pauci-immune"
      glomerulonephritis, has recently been shown to be associated with the presence of
      antineutrophil cytoplasmic antibody in the patient's circulation (but not within
      the glomerulus). The absence of the effectors of humoral immunity at the site of
      renal injury led to this investigation of the contribution of cell-mediated
      immunity to the glomerular injury in this form of glomerulonephritis. In 15
      patients presenting acutely with pauci-immune glomerulonephritis, CD3-positive T
      cells (3.7+/-2.5 [mean +/- SD] cells per glomerular cross section, [c/gcs]),
      CD45RO-positive T cells (2.7+/-1.9 c/cgs), macrophages (7.3+/-6.1 c/gcs), fibrin
      (3+), and endothelial-associated tissue factor were demonstrated to be prominent
      in glomeruli. These mediators were absent in a group of 12 patients with thin
      basement membrane disease and only occasionally observed in a group of eight
      patients with "humorally mediated"(noncrescentic) glomerulonephritis. Thus, in
      pauci-immune glomerulonephritis, there is the development of significant cell
      mediated immunity with activated T cells, macrophages, tissue factor, and fibrin
      at the site of glomerular injury, suggesting that this glomerular disease is most
      likely a manifestation of T cell-directed cognate immune injury.

PMID- 10073601
TI  - The intrarenal vascular lesions associated with primary antiphospholipid
      syndrome.
AB  - Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal
      involvement in the course of APS is still relatively unrecognized, and is
      probably underestimated. The association of anticardiolipin antibodies and/or
      lupus anticoagulant with the development of a vaso-occlusive process involving
      numerous organs is now confirmed. In a multicenter study, 16 cases of "primary"
      APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In
      all 16 cases of PAPS, there was a vascular nephropathy characterized by small
      vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of
      interlobular arteries (12 patients), recanalizing thrombi in arteries and
      arterioles (six patients), and focal cortical atrophy (10 patients). In
      combination, these led to progressive destruction of the kidney, accelerated by
      acute glomerular and arteriolar microangiopathy in five patients. Focal cortical
      atrophy is a distinctive lesion, present in 10 biopsies, and likely represents
      the histologic and functional renal analogue to the multiple cerebral infarcts
      detected on imaging studies. The clinical hallmark of this vascular nephropathy
      in PAPS is systemic hypertension, only variably associated with renal
      insufficiency, proteinuria, or hematuria. The ensemble of histologic renal
      lesions defined in this study should aid in the separation of the lesions found
      in cases of secondary APS, especially systemic lupus erythematosus, into those
      lesions related to APS and those related to the underlying disease.

PMID- 10073602
TI  - Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy
      chains lacking C(H)1.
AB  - The objective of this study was to further characterize the clinical and
      immunopathologic features of heavy chain deposition disease (HCDD), a recently
      described entity. Four patients were diagnosed as having HCDD on a kidney biopsy.
      All presented with nodular glomerulosclerosis with deposition of gamma1 heavy
      chains lacking CH1 epitopes, but without light chains. Two different patterns
      were observed in the serum. First, patients 1 and 2 had a circulating monoclonal
      IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an
      apparent molecular weight of 40 kD consistent with a complete CH1 deletion.
      Biosynthetic experiments also showed that the deleted heavy chain was produced in
      excess compared with light chains, and was secreted in vitro together with half
      Ig molecules, although these abnormal components were not detected by Western
      blot analysis of whole serum. Second, patients 3 and 4 had a circulating
      monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit,
      but serum fractionation followed by immunoblotting revealed an isolated
      monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that
      renal deposition of a CH1-deleted heavy chain circulating in low amounts in the
      serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion
      is most likely responsible for the premature secretion in blood of the heavy
      chain by a clone of plasma cells.

PMID- 10073604
TI  - Role of xanthine oxidase in passive Heymann nephritis in rats.
AB  - Passive Heymann nephritis (PHN) in rats is a model of human membranous
      nephropathy characterized by formation of subepithelial immune deposits in the
      glomerular capillary wall and complement activation. Oxygen radicals have been
      implicated in the subsequent glomerular damage which leads to proteinuria. This
      study examines the involvement of xanthine oxidase in this process. Xanthine
      oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d
      after induction of PHN, and this was associated with increased glomerular
      superoxide anion generation. Analysis of glomerular samples by Northern and
      Western blotting revealed no quantitative changes in xanthine oxidoreductase
      expression in PHN, suggesting conversion of xanthine dehydrogenase to the oxidase
      form as the cause of increased activity. Treatment of rats with tungsten, an
      inhibitor of xanthine oxidase, before induction of PHN resulted in a marked
      decrease in glomerular xanthine oxidase activity and superoxide anion generation,
      and decreased proteinuria by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53
      mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a
      pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of
      importance in the therapy of human membranous nephropathy.

PMID- 10073603
TI  - Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for
      increased IL-13 mRNA expression in relapse.
AB  - Idiopathic nephrotic syndrome of childhood is thought to be associated with T
      lymphocyte dysfunction often triggered by viral infections, with the production
      of circulating factor(s) resulting in proteinuria. In view of the conflicting
      evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in
      this disease, this study examined the mRNA expression of interleukin-2 (IL-2),
      interferon-gamma, IL-4, and IL-13 from CD4+ and CD8+ T cells in steroid
      responsive nephrotic patients in relapse and remission. Fifty-five children with
      steroid-responsive nephrotic syndrome were included in this study, together with
      34 normal controls and 24 patient controls with viral infections. RNA was
      isolated from purified CD4+ or CD8+ cells from peripheral blood and subjected to
      reverse transcription-PCR. Cytokine mRNA expression was measured
      semiquantitatively, and a cytokine index was derived from densitometric readings,
      with cyclophilin as the housekeeping gene. Both cross-sectional and paired data
      showed an increased CD4+ and CD8+ IL-13 mRNA expression in patients with
      nephrotic relapse as compared to remission, normal, and patient controls (P <
      0.008). This was also associated with increased cytoplasmic IL-13 expression in
      phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66+/-3.39%) from
      patients with nephrotic relapse compared to remission (2.59+/-1.35%) (P <
      0.0001). However, there was no significant difference in CD4+ or CD8+ IL-2,
      interferon-gamma and IL-4 mRNA expression. IL-13 is an important T cell cytokine
      with anti-inflammatory and immunomodulatory functions on B cells and monocytes.
      It is conceivable that IL-13 may act on monocytes to produce vascular
      permeability factor(s) involved in the pathogenesis of proteinuria in patients
      with relapse nephrotic syndrome.

PMID- 10073605
TI  - Angiotensin II receptor type 1 gene expression in human glomerulonephritis and
      diabetes mellitus.
AB  - The renin-angiotensin system plays an important role in the progression of
      chronic renal disease. Although the expression of renin and angiotensin
      converting enzyme in experimental and human renal disease has been well
      characterized, no information is available regarding human angiotensin type 1
      (AT1) receptor expression. The net effect of renin depends on AT1 receptor
      expression, among other factors. Receptor expression was determined in renal
      biopsy samples (including all tissue components) and isolated glomeruli from
      patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin
      dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor
      free tissue from tumor nephrectomies served as controls. Human AT1 receptor gene
      expression was determined by quantitative reverse transcription-PCR, using an AT1
      receptor deletion mutant as the internal standard. In whole biopsy samples from
      37 patients with various types of GN, AT1 receptor mRNA levels were lower,
      compared with nine control biopsy samples (P < 0.001). AT1 receptor mRNA levels
      were also significantly lower (P < 0.001) in eight samples from patients with
      diabetic nephropathy. In microdissected glomeruli, AT1 receptor gene expression
      was significantly lower in samples from patients (n = 22) with various types of
      GN, compared with 12 microdissected tumor nephrectomy control samples (P <
      0.0023). It is concluded that AT1 receptor mRNA expression is low in glomeruli of
      patients with chronic renal disease. This may reflect a regulatory response to
      (inappropriately) high intrarenal angiotensin II concentrations.

PMID- 10073606
TI  - "The FSGS factor:" enrichment and in vivo effect of activity from focal segmental
      glomerulosclerosis plasma.
AB  - A circulating causative factor has been postulated in focal segmental
      glomerulosclerosis (FSGS). It has been shown that serum or plasma from some FSGS
      increases glomerular albumin permeability (Palb) in vitro. Palb greater than 0.5
      (i.e., FS activity) is associated with recurrence after transplantation.
      Specimens from 15 FSGS patients were studied to document the presence of a
      permeability factor, to isolate this factor, to characterize its biochemical
      properties, and to show its effect in vivo. Total lipids were extracted by
      chloroform/methanol (2: 1); FS activity was absent from total lipid extract.
      Chylomicrons and lipoproteins were removed from the plasma with dextran sulfate,
      followed by sequential precipitation of proteins at 50 and 70% ammonium sulfate
      saturation. FS activity was retained in the 70% ammonium sulfate supernatant and
      exhibited a 100-fold purification. FS activity was lost after heating at 100
      degrees C for 10 min or after protease digestion. Under nondenaturing conditions,
      electrophoresis of the FSGS 70% supernatant showed a prominent low molecular
      weight band that was not evident in the 70% supernatant from normal plasma.
      Dialysis and centrifugation-based membrane ultrafiltration of the FSGS factor
      indicated a molecular size between 30 and 50 kD. Injection of the 70% FSGS
      supernatant into rats caused a threefold increase in urine protein in collections
      from 6 to 24 h after injection. No increase in proteinuria occurred in rats
      injected with 70% supernatant from normal individuals. It is concluded that the
      FSGS factor is a low molecular weight protein with the potential to increase Palb
      in vitro and to cause proteinuria in vivo.

PMID- 10073607
TI  - Intranephron distribution and regulation of endothelin-converting enzyme-1 in
      cyclosporin A-induced acute renal failure in rats.
AB  - Endothelin-1 (ET-1) is thought to play a significant role in acute renal failure
      induced by cyclosporin A (CsA). The cDNA sequence encoding endothelin-converting
      enzyme-1 (ECE-1), which produces the active form of ET-1 from big ET-1, was
      recently reported. To elicit the role of ECE-1 in the glomerular and tubular
      dysfunction induced by CsA, the effects of CsA on mRNA and protein expression of
      ECE-1 in rat kidney and on mRNA expression of prepro-ET-1 and ET A- and B-type
      receptors in glomeruli were studied. ECE-1 mRNA was detected in glomeruli and in
      whole nephron segments. ECE-1 mRNA expression was downregulated in all nephron
      segments at 24 h after CsA injection. Protein levels were also downregulated in
      glomeruli and in the outer and inner medulla. CsA rapidly increased prepro-ET-1
      mRNA expression in glomeruli at 30 to 60 min after injection; this rapid increase
      was followed by an increase in plasma ET-1 levels. These increases were followed
      by decreased expression of ECE-1, ET A-type receptor, and ET B-type receptor mRNA
      at 6 h after injection, and serum creatinine levels were increased at 24 h after
      CsA injection. It is suggested that downregulation of glomerular and tubular ECE
      1 expression may be caused by increased ET-1 synthesis in CsA-induced acute renal
      failure.

PMID- 10073608
TI  - Renal function in high-output heart failure in rats: role of endogenous
      natriuretic peptides.
AB  - The physiologic and pathophysiologic importance of natriuretic peptides (NP) has
      been imperfectly defined. The diminished renal responses to exogenous atrial NP
      in heart failure have led to the perception that the endogenous NP system might
      be less effective and thus contribute to renal sodium retention in heart failure.
      This study tests the hypothesis that in experimental heart failure, the renal
      responses to an acute volume load are still dependent on the NP system. The
      specific antagonist HS-142-1 was used to block the effects of NP in a model of
      high-output heart failure induced by an aortocaval shunt. Plasma cGMP levels and
      renal cGMP excretion were significantly lower in shunted and sham-operated rats
      receiving HS-142-1, compared with vehicle-treated controls, indicating effective
      blockade of guanylate cyclase-coupled receptors. Baseline sodium excretion and
      urine flow rate were lower in HS-142-1-treated sham-operated rats (15.2+/-1.1
      microl/min versus 27.5+/-3.1 microl/min with vehicle, P < 0.001) and in HS-142-1
      treated shunted rats (8.1+/-1.3 microl/min versus 19.9+/-2.3 microl/min with
      vehicle, P < 0.001). After an acute volume load, the diuretic and natriuretic
      responses were attenuated by HS-142-1 in control and shunted rats. The renal
      responses were reduced by HS-142-1 to a significantly greater extent in shunted
      rats than in control rats. HS-142-1 did not induce any significant systemic
      hemodynamic changes in either group, nor did it alter renal blood flow. However,
      the GFR in HS-142-1-treated shunted rats was lower than that in vehicle-treated
      shunted rats, both at baseline (0.6+/-0.3 ml/min versus 2.1+/-0.4 ml/min with
      vehicle, P < 0.05) and after an acute volume load (1.2+/-0.4 ml/min versus 2.6+/
      0.4 ml/min with vehicle, P = 0.01), whereas no such effect was observed in
      control rats. These data indicate that the maintenance of basal renal function
      and the responses to acute volume loading are dependent on the NP system. The NP
      seem to be of particular importance for the maintenance of GFR in this model of
      experimental heart failure. These observations provide new insights into the
      importance of the renal NP system in heart failure.

PMID- 10073609
TI  - Prevalence and clinical outcome associated with preexisting malnutrition in acute
      renal failure: a prospective cohort study.
AB  - Malnutrition is a frequent finding in hospitalized patients and is associated
      with an increased risk of subsequent in-hospital morbidity and mortality. Both
      prevalence and prognostic relevance of preexisting malnutrition in patients
      referred to nephrology wards for acute renal failure (ARF) are still unknown.
      This study tests the hypothesis that malnutrition is frequent in such clinical
      setting, and is associated with excess in-hospital morbidity and mortality. A
      prospective cohort of 309 patients admitted to a renal intermediate care unit
      during a 42-mo period with ARF diagnosis was studied. Patients with malnutrition
      were identified at admission by the Subjective Global Assessment of nutritional
      status method (SGA); nutritional status was also evaluated by anthropometric,
      biochemical, and immunologic parameters. Outcome measures included in-hospital
      mortality and morbidity, and use of health care resources. In-hospital mortality
      was 39% (120 of 309); renal replacement therapies (hemodialysis or continuous
      hemofiltration) were performed in 67% of patients (206 of 309); APACHE II score
      was 23.1+/-8.2 (range, 10 to 52). Severe malnutrition by SGA was found in 42% of
      patients with ARF; anthropometric, biochemical, and immunologic nutritional
      indexes were significantly reduced in this group compared with patients with
      normal nutritional status. Severely malnourished patients, as compared to
      patients with normal nutritional status, had significantly increased morbidity
      for sepsis (odds ratio [OR] 2.88; 95% confidence interval [CI], 1.53 to 5.42, P <
      0.001), septic shock (OR 4.05; 95% CI, 1.46 to 11.28, P < 0.01), hemorrhage (OR
      2.98; 95% CI, 1.45 to 6.13, P < 0.01), intestinal occlusion (OR 5.57; 95% CI,
      1.57 to 19.74, P < 0.01), cardiac dysrhythmia (OR 2.29; 95% CI, 1.36 to 3.85, P <
      0.01), cardiogenic shock (OR 4.39; 95% CI, 1.83 to 10.55, P < .001), and acute
      respiratory failure with mechanical ventilation need (OR 3.35; 95% CI, 3.35 to
      8.74, P < 0.05). Hospital length of stay was significantly increased (P < 0.01),
      and the presence of severe malnutrition was associated with a significant
      increase of in-hospital mortality (OR 7.21; 95% CI, 4.08 to 12.73, P < 0.001).
      Preexisting malnutrition was a statistically significant, independent predictor
      of in-hospital mortality at multivariable logistic regression analysis both with
      comorbidities (OR 2.02; 95% CI, 1.50 to 2.71, P < 0.001), and with comorbidities
      and complications (OR 2.12; 95% CI, 1.61 to 2.89, P < 0.001). Malnutrition is
      highly prevalent among ARF patients and increases the likelihood of in-hospital
      death, complications, and use of health care resources.

PMID- 10073610
TI  - Asymmetric dimethylarginine plasma concentrations differ in patients with end
      stage renal disease: relationship to treatment method and atherosclerotic
      disease.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial
      nitric oxide (NO) synthase. Its concentration is elevated in patients with end
      stage renal disease (ESRD), in part because it is excreted via the kidneys. In
      this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L
      arginine were determined in relation to plasma nitrate levels (as an index of NO
      formation) for a group of 80 patients with ESRD. The effects of two treatment
      methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of
      the presence of atherosclerotic disease were evaluated. Forty-three patients
      receiving HD and 37 patients receiving PD were compared with healthy control
      subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC,
      using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels
      were determined by gas chromatography-mass spectrometry. Predialysis ADMA
      concentrations in HD-treated patients were approximately sixfold higher than
      those in the control group (6.0+/-0.5 versus 1.0+/-0.1 micromol/L; P < 0.05).
      Plasma nitrate concentrations were significantly lower in HD-treated patients,
      which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels
      and nitrate concentrations in PD-treated patients were similar to those in
      control subjects. Plasma L-arginine concentrations were not significantly
      decreased in patients with ESRD. ADMA concentrations were significantly decreased
      5 h after HD, compared with baseline values. ADMA levels were significantly
      higher in HD-treated patients with manifest atherosclerotic disease than in HD
      treated patients without atherosclerotic disease (7.31+/-0.70 versus 3.95+/-0.52
      micromol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD
      treated patients exhibit significantly lower ADMA levels than do HD-treated
      patients. Accumulation of ADMA may be a risk factor for the development of
      endothelial dysfunction and cardiovascular disease in patients with ESRD.

PMID- 10073611
TI  - Quantifying the effect of changes in the hemodialysis prescription on effective
      solute removal with a mathematical model.
AB  - One potential benefit of chronic hemodialysis (HD) regimens of longer duration or
      greater frequency than typical three-times-weekly schedules is enhanced solute
      removal over a relatively wide molecular weight spectrum of uremic toxins. This
      study assesses the effect of variations in HD frequency (F: per week), duration
      (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady
      state concentration profiles of five surrogates: urea (U), creatinine (Cr),
      vancomycin (V), inulin (I), and beta2-microglobulin (beta2M). The regimens
      assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB =
      350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E
      (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100. HD was simulated
      with a variable-volume double-pool model, which was solved by numerical
      integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and
      beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for
      V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle
      molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40
      ml/min were used for U, Cr, V, I, and beta2M, respectively, For each
      solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was
      calculated as a dimensionless value normalized to the regimen A EKR, which was
      13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively.
      For regimens B, C, D, and E, respectively, these normalized EKR values were U:
      1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21,
      and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19. The
      extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16%
      (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28%
      (beta2M). The following conclusions can be made: (1) Relative to a standard three
      times-weekly HD regimen of approximately the same total (weekly) treatment
      duration, a daily/short-time regimen results in modest (3 to 6%) increases in
      effective small solute and MM removal. (2) Relative to a standard three-times
      weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in
      comparable effective small solute removal and progressive increases in MM and
      beta2M removal. A daily low-flow/long-time regimen substantially increases the
      effective removal of all solutes.

PMID- 10073612
TI  - Hematocrit level and associated mortality in hemodialysis patients.
AB  - Although a number of clinical studies have shown that increased hematocrits are
      associated with improved outcomes in terms of cognitive function, reduced left
      ventricular hypertrophy, increased exercise tolerance, and improved quality of
      life, the optimal hematocrit level associated with survival has yet to be
      determined. The association between hematocrit levels and patient mortality was
      retrospectively studied in a prevalent Medicare hemodialysis cohort on a national
      scale. All patients survived a 6-mo entry period during which their hematocrit
      levels were assessed, from July 1 through December 31, 1993, with follow-up from
      January 1 through December 31, 1994. Patient comorbid conditions relative to
      clinical events and severity of disease were determined from Medicare claims data
      and correlated with the entry period hematocrit level. After adjusting for
      medical diseases, our results showed that patients with hematocrit levels less
      than 30% had significantly higher risk of all-cause (12 to 33%) and cause
      specific death, compared to patients with hematocrits in the 30% to less than 33%
      range. Without severity of disease adjustment, patients with hematocrit levels of
      33% to less than 36% appear to have the lowest risk for all-cause and cardiac
      mortality. After adjusting for severity of disease, the impact of hematocrit
      levels of 33% to less than 36% is vulnerable to the patient sample size but also
      demonstrates a further 4% reduced risk of death. Overall, these findings suggest
      that sustained increases in hematocrit levels are associated with improved
      patient survival.

PMID- 10073613
TI  - Carl W. Gottschalk's contributions to elucidating the urinary concentrating
      mechanism.

PMID- 10073614
TI  - Regulation of thick ascending limb transport by vasopressin.

PMID- 10073615
TI  - Regulation of renal urea transporters.
AB  - Urea is important for the conservation of body water due to its role in the
      production of concentrated urine in the renal inner medulla. Physiologic data
      demonstrate that urea is transported by facilitated and by active urea
      transporter proteins. The facilitated urea transporter (UT-A) in the terminal
      inner medullary collecting duct (IMCD) permits very high rates of transepithelial
      urea transport and results in the delivery of large amounts of urea into the
      deepest portions of the inner medulla where it is needed to maintain a high
      interstitial osmolality for concentrating the urine maximally. Four isoforms of
      the UT-A urea transporter family have been cloned to date. The facilitated urea
      transporter (UT-B) in erythrocytes permits these cells to lose urea rapidly as
      they traverse the ascending vasa recta, thereby preventing loss of urea from the
      medulla and decreasing urine-concentrating ability by decreasing the efficiency
      of countercurrent exchange, as occurs in Jk null individuals (who lack Kidd
      antigen). In addition to these facilitated urea transporters, three sodium
      dependent, secondary active urea transport mechanisms have been characterized
      functionally in IMCD subsegments: (1) active urea reabsorption in the apical
      membrane of initial IMCD from low-protein fed or hypercalcemic rats; (2) active
      urea reabsorption in the basolateral membrane of initial IMCD from furosemide
      treated rats; and (3) active urea secretion in the apical membrane of terminal
      IMCD from untreated rats. This review focuses on the physiologic, biophysical,
      and molecular evidence for facilitated and active urea transporters, and
      integrative studies of their acute and long-term regulation in rats with reduced
      urine-concentrating ability.

PMID- 10073616
TI  - Physiology and pathophysiology of renal aquaporins.
AB  - The discovery of aquaporin membrane water channels by Agre and coworkers answered
      a long-standing biophysical question of how water specifically crosses biologic
      membranes, and provided insight, at the molecular level, into the fundamental
      physiology of water balance and the pathophysiology of water balance disorders.
      Of nine aquaporin isoforms, at least six are known to be present in the kidney at
      distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is
      extremely abundant in the proximal tubule and descending thin limb, where it
      appears to provide the chief route for proximal nephron water reabsorption. AQP2
      is abundant in the collecting duct principal cells and is the chief target for
      vasopressin to regulate collecting duct water reabsorption. Acute regulation
      involves vasopressin-regulated trafficking of AQP2 between an intracellular
      reservoir and the apical plasma membrane. In addition, AQP2 is involved in
      chronic/adaptational regulation of body water balance achieved through regulation
      of AQP2 expression. Importantly, multiple studies have now identified a critical
      role of AQP2 in several inherited and acquired water balance disorders. This
      concerns inherited forms of nephrogenic diabetes insipidus and several, much more
      common acquired types of nephrogenic diabetes insipidus where AQP2 expression
      and/or targeting are affected. Conversely, AQP2 expression and targeting appear
      to be increased in some conditions with water retention such as pregnancy and
      congestive heart failure. AQP3 and AQP4 are basolateral water channels located in
      the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower
      abundance at several sites including the proximal tubule. This review focuses
      mainly on the role of AQP2 in water balance regulation and in the pathophysiology
      of water balance disorders.

PMID- 10073617
TI  - Sensitized cells come of age: a new era in renal immunology with important
      therapeutic implications.

PMID- 10073618
TI  - Lithium intoxication.

PMID- 10073619
TI  - On the mechanism of action of aldosterone on sodium transport: the role of
      protein synthesis. 1963.

PMID- 10073620
TI  - Developing a clinical competency examination in radiology: part I--test
      structure.
AB  - BACKGROUND: There is a need for radiology educational outcome measures that
      evaluate clinical competency. This is the first of two articles introducing a
      clinical competency examination in radiology. This first article describes the
      evolution and structure of the examination. The second article presents the
      results of two administrations of the examination and evaluates possible outcome
      predictors. OBJECTIVE: To develop a measure of clinical competency in radiology.
      DESIGN: Descriptive. METHODS: A test was developed to simulate the radiologic
      interpretive skills needed in clinical chiropractic practice. Students were timed
      as they responded to questions regarding the localization, categorization,
      management, and identification of pathologic conditions presented on plain film
      images of the spine and chest. Twenty-five radiographic cases were displayed at
      individual viewbox stations, and student responses to the 4 questions were
      compared with the consensus responses of 2 radiology instructors. RESULTS: Two
      versions of the test, using different cases, were given to the same ninth
      trimester class of 210 chiropractic students in a 10-trimester program. Of the
      210 students, 116 (55.2%; 86 men and 30 women) took version 1 of the examination,
      and 1 month later 181 (86.2%: 138 men and 43 women) took version 2 of the
      examination. Student comments after each examination were favorable. CONCLUSION:
      The test structure uniquely provides information related to the student's ability
      to localize, categorize, manage, and identify pathologic conditions on imaging
      studies. At present the examination is instructor time intensive; further
      refinement is needed before wide implementation can occur.

PMID- 10073621
TI  - Developing a clinical competency examination in radiology: part II--test results.
AB  - BACKGROUND: This is the second of two articles introducing a clinical competency
      examination in radiology. The first article described the structure,
      administration, and postexamination student comments for two versions of the
      radiology competency examination. This article reports the results obtained from
      these two administrations of the examinations. OBJECTIVE: To measure and identify
      potential outcome predictors of student aptitude in clinical film interpretation.
      DESIGN: Experimental. METHODS: An examination was developed to simulate the
      radiologic interpretive skills needed in clinical chiropractic practice. Two
      versions of the examination were given to a class of 210 ninth trimester students
      in a 10-trimester chiropractic program. Linear regression and bivariate
      correlations were performed on possible predictors of student success and test
      scores on the version 2 examination. RESULTS: On version 1 of the examination,
      students were able to identify an average of 59.6% of the normal cases as normal
      and 51.6% of abnormal cases as abnormal. On version 2, 55.6% of the normal cases
      were recognized as normal and 58.2% of abnormal cases as abnormal. On both
      versions, students were less successful at correctly categorizing, managing, or
      naming pathologic conditions they found. Of the predictors evaluated, only the
      students' grades in the third radiology course (tumors, arthritides, and
      extremity trauma) and the scores on the diagnostic imaging section of National
      Boards part II were significant predictors. DISCUSSION: Our results should cause
      some concern for educators who use content-based radiology curricula. Students
      demonstrated poor abilities to recognize, categorize, manage, and identify common
      radiographic pathologic conditions. Educators cannot rely on National Board
      scores and course grades to determine student clinical competency. More radiology
      clinical competency exercises that emphasize film interpretation need to be
      incorporated into content-based curricula.

PMID- 10073622
TI  - Validation of the force and frequency characteristics of the activator adjusting
      instrument: effectiveness as a mechanical impedance measurement tool.
AB  - OBJECTIVE: To determine the dynamic force-time and force-frequency
      characteristics of the Activator Adjusting Instrument and to validate its
      effectiveness as a mechanical impedance measurement device; in addition, to
      refine or optimize the force-frequency characteristics of the Activator Adjusting
      Instrument to provide enhanced dynamic structural measurement reliability and
      accuracy. METHODS: An idealized test structure consisting of a rectangular steel
      beam with a static stiffness similar to that of the human thoracolumbar spine was
      used for validation of a method to determine the dynamic mechanical response of
      the spine. The Activator Adjusting Instrument equipped with a load cell and
      accelerometer was used to measure forces and accelerations during mechanical
      excitation of the steel beam. Driving point and transfer mechanical impedance and
      resonant frequency of the beam were determined by use of a frequency spectrum
      analysis for different force settings, stylus masses, and stylus tips. Results
      were compared with beam theory and transfer impedance measurements obtained by
      use of a commercial electronic PCB impact hammer. RESULTS: The Activator
      Adjusting Instrument imparted a very complex dynamic impact comprising an initial
      high force (116 to 140 N), short duration pulse (<0.1 ms) followed by several
      lower force (30 to 100 N), longer duration impulses (1 to 5 ms). The force
      profile was highly reproducible in terms of the peak impulse forces delivered to
      the beam structure (<8% variance). Spectrum analysis of the Activator Adjusting
      Instrument impulse indicated that the Activator Adjusting Instrument has a
      variable force spectrum and delivers its peak energy at a frequency of 20 Hz.
      Added masses and different durometer stylus tips had very little influence on the
      Activator Adjusting Instrument force spectrum. The resonant frequency of the beam
      was accurately predicted by both the Activator Adjusting Instrument and
      electronic PCB impact hammer, but variations in the magnitude of the driving
      point impedance at the resonant frequency were high (67%) compared with the
      transfer impedance measurements obtained with the electronic PCB impact hammer,
      which had a more uniform force spectrum and was more repeatable (<10% variation).
      The addition of a preload-control frame to the Activator Adjusting Instrument
      improved the characteristics of the force frequency spectrum and repeatability of
      the driving point impedance measurements. CONCLUSION: These findings indicate
      that the Activator Adjusting Instrument combined with an integral load cell and
      accelerometer was able to obtain an accurate description of a steel beam with
      readily identifiable geometric and dynamic mechanical properties. These findings
      support the rationale for using the device to assess the dynamic mechanical
      behavior of the vertebral column. Such information would be useful for SMT and
      may ultimately be used to evaluate the [corrected] biomechanical effectiveness of
      various manipulative, surgical, and rehabilitative spinal procedures.

PMID- 10073623
TI  - Experts' opinions on complementary/alternative therapies for low back pain.
AB  - BACKGROUND: Complementary/alternative therapies are used for low back pain more
      frequently than for any other indication, yet evidence for or against their
      efficacy is fragmentary. Notwithstanding this void, the high prevalence of such
      therapies drives their integration into our health care systems. Expert opinions
      on the use of complementary/alternative therapies for low back pain could
      therefore be helpful until more data from randomized, controlled trials become
      available. OBJECTIVE: A postal questionnaire survey was designed to generate
      opinion from a systematically identified expert panel on the clinical
      effectiveness of complementary/alternative therapies for low back pain. METHODS:
      Computerized searches were conducted to systematically identify by objective
      criteria 50 clinical experts on low back pain. Each panel member received a
      questionnaire to assess the perceived clinical effectiveness of
      complementary/alternative therapies for 4 defined categories of low back pain.
      RESULTS: For acute uncomplicated low back pain, osteopathy and chiropractic were
      rated as effective by most experts. For chronic uncomplicated low back pain, most
      experts considered acupuncture as effective. Experts perceived homeopathy
      generally as ineffective for any type of low back pain. Clinical experience with
      herbalism as a treatment for low back pain was insufficient to form an opinion.
      CONCLUSION: Experts' opinion is in favor of the effectiveness of osteopathy and
      chiropractic for acute uncomplicated low back pain. Acupuncture is judged to be
      of some value for chronic, uncomplicated low back pain. Homeopathy is perceived
      as ineffective for any type of low back pain. Insufficient experience with
      herbalism as a treatment for low back pain prevents firm conclusions.

PMID- 10073624
TI  - Changes and implications of blood flow velocity of the vertebral artery during
      rotation and extension of the head.
AB  - OBJECTIVE: To study the effects of extension and extension-rotation of the head
      on the blood flow velocity of the vertebral artery experimentally and clinically.
      DESIGN: Randomized experimental clinical study. SETTING: Institute of Clinical
      Anatomy and Biomechanics and the Department of Ultrasound, NanFang Hospital of
      the First Military Medical University, Guangzhou, China. SUBJECTS: The fresh
      spines from T1-2 to the occipital bone were obtained from persons who died of
      acute brain death (n = 10). For the transcranial Doppler measurement, 27
      asymptomatic subjects with routine physical examination results and 23 students
      from the above-mentioned university took part in the test. INTERVENTIONS: The
      instillation experiment in the cadavers was made. Clinical measurements of blood
      flow velocity in the vertebral artery in the subjects and students were taken and
      recorded. MAIN OUTCOME MEASURES: Changes in the drop of the vertebral artery were
      measured by the instillation test in the experimental sample. The blood flow
      velocity was measured with transcranial Doppler sonography during extension and
      extension-rotation of the head. RESULTS: During one-sided rotation of the head
      with extension of the head, measurements in the contralateral vertebral artery
      and the bilateral vertebral arteries were both reduced in the instillation
      experiment. The blood flow velocity in the bilateral vertebral arteries decreased
      during extension and extension-rotation of the head in the subjects and the
      students. The pulsatility index in the right vertebral arteries increased more
      than that in the left in extreme extension and that in the bilateral vertebral
      arteries in neutral position. CONCLUSIONS: Extreme rotation and extension are
      dangerous to patients who have abnormal vertebral arteries when extreme rotatory
      and extension manipulations are applied. Doctors should be very careful when
      rotating the patient's head to the right side.

PMID- 10073625
TI  - Low back pain and the lumbar intervertebral disk: clinical considerations for the
      doctor of chiropractic.
AB  - BACKGROUND: Low back pain exists in epidemic proportions in the United States.
      Studies that demonstrate innervation to the intervertebral disk provide evidence
      that may account for instances of discogenic low back pain encountered in general
      medical and chiropractic practice. Many patients and health care practitioners
      believe that intervertebral disk lesions require surgery as the only method of
      treatment that will result in satisfactory outcome. Surgery rates vary widely
      across geographic regions. Only one randomized prospective study exists that
      compares surgical and nonsurgical treatment; it demonstrated essentially equal
      outcomes in the long run. OBJECTIVE: To review specific aspects of the
      examination, history, imaging, and treatment of patients with suspected
      intervertebral disk lesions and to provide guidelines for conservative
      management, imaging, and relative and absolute indications for surgical referral.
      DATA SOURCES: Review articles, texts, and original articles from indexed refereed
      sources that discuss the lumbar intervertebral disk in regard to patient history,
      physical examination, imaging, treatment, and referral for surgery. RESULTS:
      Patients with low back pain who do not present with so-called red flags (fever,
      history of cancer, unexplained weight loss, urinary tract infection, intravenous
      drug use, saddle anesthesia, or prolonged use of corticosteroids) may be treated
      initially with conservative methods. Imaging studies are helpful in determining
      the patient's diagnosis, and computed tomography, magnetic resonance imaging, or
      other special imaging studies should be ordered judiciously. The only
      prospective, randomized study of conservative versus surgical management of
      herniated lumbar intervertebral disk lesions indicates both methods provide
      adequate outcome in the long run. Little consensus exists on the best method of
      management for patients with intervertebral disk lesions without absolute
      indications for surgery. CONCLUSION: Patients should be screened for "red flags"
      to determine whether they are candidates for conservative treatment. Magnetic
      resonance imaging is perhaps the most practical imaging study for evaluation of
      lumbar disk lesions because it involves no use of ionizing radiation and because
      magnetic resonance imaging has other advantages over computed tomographic
      scanning such as excellent delineation of soft tissue structures, direct
      multiplanar imaging, and excellent characterization of medullary bone.
      Provocation computed tomography-diskography is an invasive procedure and should
      be reserved for patients with normal magnetic resonance imaging findings and
      continuing severe pain who have not been helped by conservative treatment
      attempts and for whom surgical intervention is contemplated. Both conservative
      and surgical interventions have been shown to be effective in the treatment of
      discogenic and radicular pain syndromes.

PMID- 10073626
TI  - Manipulative management of post-Colles' fracture weakness and diminished active
      range of motion.
AB  - OBJECTIVE: To discuss the management of a patient with wrist weakness and a
      diminution in active range of motion resulting from Colles' fracture. CLINICAL
      FEATURES: A 58-year-old woman complained of persistent loss of grip strength and
      mobility in her right wrist. These complaints were from Colles' fracture
      occurring 19 months before initiation of care. Dynamometer and goniometric
      testing revealed significant loss of grip strength and range of motion compared
      with the uninvolved, nondominant wrist. INTERVENTION AND OUTCOME: Specific joint
      manipulation for improvement in mobility and grip strength of the wrist was
      performed. The patient's right wrist was evaluated for grip strength and active
      range of motion over a 3-week period, providing a baseline of function before
      treatment. After 4 visits of baseline measurements, a series of 4 treatments and
      4 reevaluations was performed. The patient exhibited a significant increase in
      grip strength and active range of motion. CONCLUSION: Appropriate intervention of
      chiropractic manipulation and examination procedures culminated in a successful
      resolution of this case. When such cases are recognized, appropriate management
      may occur conservatively with judicious application of joint manipulation and
      reevaluation procedures.

PMID- 10073627
TI  - Effects of altering cycling technique on gluteus medius syndrome.
AB  - OBJECTIVE: We discuss how altering the cycling technique of a cyclist receiving
      periodic chiropractic care helped in the management of gluteus medius syndrome.
      CLINICAL FEATURES: A 24-year-old male amateur cyclist had numbness and tingling
      localized to a small region on the superior portion of the right buttock. The
      area involved demonstrated paresthesia to light touch sensory evaluation. The
      cyclist had received chiropractic adjustments 2 days before the onset of the
      symptoms. One week earlier, the patient began riding a new bicycle with different
      gearing than his previous one. Manual-resisted muscle testing created soreness in
      the lumbosacral area and buttocks. Trigger points were identified in the right
      gluteus medius. Standing lumbar spine flexion was 70 degrees, limited by tight
      hamstrings. INTERVENTION AND OUTCOME: Because the patient was already receiving
      periodic chiropractic care, no passive therapy was used. Patient education
      regarding the difference in gear selection in bicycles of a higher quality was
      provided. He was instructed to train in lower gears than he had previously used
      and to maintain a cadence of 70 to 90 revolutions of the pedals per minute. After
      2 days, the paresthesia on the right buttock resolved. The trigger points were
      only mildly tender with minimal residual soreness of the involved muscles.
      CONCLUSION: Management of gluteus medius syndrome by altering the cadence and
      gear development for a bicyclist is discussed. Either frank or cumulative injury
      to the gluteus medius muscle is the typical etiologic factor for this syndrome.
      Repetitive strain of the patient's gluteus medius muscle as a result of poor
      cycling technique appeared to be the cause here. Knowledge of bicycle fitting,
      training techniques, and bicycle mechanics appeared necessary to resolve the
      problem.

PMID- 10073628
TI  - Toward an evidence-based model for chiropractic education and practice.

PMID- 10073629
TI  - Informed consent: an Australian case study.

PMID- 10073630
TI  - Joint complex dysfunction, a novel term to replace subluxation/subluxation
      complex: etiological and treatment considerations.

PMID- 10073631
TI  - Corneal swelling and extended wear.

PMID- 10073632
TI  - A look back.

PMID- 10073633
TI  - Achieving additional myopic correction in undercorrected radial keratotomy eyes
      using the Lexington RK splint design.
AB  - PURPOSE: To reshape or flatten the corneas of post-radial keratotomy (RK)
      patients with residual myopia to improve uncorrected vision. METHODS: Twenty-one
      eyes (12 patients) with undercorrected RK results were fit with the Lexington RK
      splint, a multicurve plateau concept RGP contact lens. RESULTS: After wearing the
      lens an average of 6.1 months, undercorrected visual acuity improved an average
      3.4 lines; change in spherical equivalent averaged 0.77 D; and flat K change
      averaged 0.75 D. Seventeen of 21 eyes (81%) demonstrated improved uncorrected
      vision. Nine eyes (43%) subsequently had a decrease in vision after discontinuing
      lens wear. Patients fit within 7 months of their last RK procedure were more
      likely to achieve optimal results. Sixty-two percent of this group did not
      require glasses or contact lenses (range: 4 to 21 months). CONCLUSIONS: A well
      designed and fit plateau RGP contact lens can manipulate the healing post-RK
      cornea.

PMID- 10073634
TI  - Cytotoxicity evaluation of multipurpose contact lens solutions using an in vitro
      test battery.
AB  - PURPOSE: Many in vitro alternatives to eye irritation testing are not mechanism
      specific and do not employ ocular cell lines. We have developed an effective and
      reliable test battery that reveals toxicity mechanisms of contact lens solutions
      on cell metabolism and proliferation. METHODS: Cytotoxicity endpoints were
      quantified using bovine corneal epithelial cultures in 96-well microplates. A
      kenacid blue assay provided information on total cell protein, while lactate
      production and alamarBlue assays served as indicators of aerobic/anaerobic
      metabolism and redox state of cells grown in serum-free Dulbecco's modified
      Eagle's/Ham's F12 medium (DMEM/F12). Concentrations (% v/v) causing 10-90%
      inhibition of the control assay responses were used for correlations with in vivo
      data. RESULTS: Cytotoxicities of contact lens solutions correlated better with
      irritant symptoms than with corneal staining, and were ranked as follows: Lens
      Plus << Opti-Free < or = ContaClair < or = ReNu. Lens Plus was not toxic to cell
      glycolysis, respiration, and proliferation for up to 20% v/v. However, the multi
      purpose solutions inhibited these endpoints in a concentration-dependent manner.
      Opti-Free and ReNu, containing Dymed and Polyquad (ammonium surfactants), showed
      non-specific cell inhibition. The lactate production assay had a flatter log
      concentration-response curve than the other two assays. CONCLUSIONS: The proposed
      biochemically-based test battery using the target corneal epithelium has the
      potential to be a simple and effective method for screening and defining toxicity
      profiles of contact lens care solutions. The model can be applicable to small- or
      large-scale testing programs and research and development of new ocular products.

PMID- 10073635
TI  - Clinical assessment of the piggyback bifocal contact lens system.
AB  - PURPOSE: We performed a qualitative and quantitative assessment of contact lens
      performance at 1 and 6 months among 24 patients enrolled in the Piggyback Bifocal
      Contact Lens Study. METHODS: We fit 24 presbyopic patients with the Piggyback
      Bifocal Contact Lens System (i.e., a plano soft lens with a 9.4 mm cutout portion
      on which a bifocal RGP lens rides or "piggybacks"). Patients were evaluated prior
      to inclusion in the study and then at one month and six months after obtaining
      their lenses. Evaluations included slit lamp examination, evaluation of visual
      acuity at near and distance, and subjective rating of the patients' comfort.
      RESULTS: At one month, 61% of patients had Snellen acuities of 20/30 or better,
      79% had near acuities of J2 or better, and 60% rated their comfort as good or
      very good. At six months, 100% of patients had Snellen acuities of 20/30 or
      better, 90% had near acuities of J2 or better, and 86% of patients rated their
      comfort as good or better. Twelve patients did not complete the study due to
      their decision to drop the study. CONCLUSIONS: The Piggyback Bifocal Contact Lens
      System is a well-tolerated, satisfactory means of optical correction for the
      motivated presbyope.

PMID- 10073636
TI  - Omafilcon A (Proclear) soft contact lenses in a dry eye population.
AB  - PURPOSE: We conducted a 3-month, randomized, comparative cross-over study to
      evaluate the clinical performance of lenses manufactured from omafilcon A on
      subjects with signs and symptoms of dry eye. The subjects' own daily wear soft
      lenses were used as controls. METHODS: Seventy-six subjects with objective
      evidence of dry eye, as defined in the NEI/Industry Workshop Report 1995, were
      fit with either the omafilcon A lenses (Proclear) or new control lenses. Subjects
      wore the lenses for 6 weeks and then crossed over to bilateral wear of the other
      lenses for an additional 6 weeks. During each part of the study, we examined
      subjects at 1 week, 1 month, and 6 weeks. Signs and symptoms of dry eye were
      evaluated, and on-eye dehydration of the lens was assessed. RESULTS: When the
      subjects were wearing the omafilcon A lenses, there was a statistically
      significant improvement in a number of subjective parameters including comfort,
      dryness, frequency of eye irritation, and frequency of burning. We found
      significantly less on-eye dehydration of the lens and fluorescein corneal
      staining with the omafilcon A lenses. CONCLUSIONS: This study indicated that the
      daily wear of omafilcon A lenses provided better comfort, fewer symptoms, less on
      eye dehydration, and less fluorescein corneal staining than other soft daily wear
      contact lenses in subjects with mild to moderate dry eye.

PMID- 10073637
TI  - Comparison of contrast sensitivity in different soft contact lenses and
      spectacles.
AB  - PURPOSE: To compare the visual performance of soft contact lenses and spectacles.
      METHODS: Twenty eyes of ten patients were examined. Each patient was fit with
      Acuvue, Cibasoft, and Biomedics contact lenses in random order. LogMar visual
      acuity and contrast sensitivity using the VectorVision CSV-1000 were measured.
      RESULTS: There was no significant difference in visual acuity between any contact
      lenses (P=.15). Contrast sensitivity at 12 cycles/degree was significantly lower
      for the Cibasoft lens compared to spectacles (P=.04). There was no significant
      difference between spectacles and contact lenses for remaining spatial
      frequencies (P=.07-.35). CONCLUSIONS: Visual acuity appears to be an insensitive
      method for evaluating soft contact lenses. The lathe-cut manufacturing process
      may be responsible for reduced visual function compared to cast-molded lenses.
      Further study in this area is needed.

PMID- 10073638
TI  - Comparative antimicrobial efficacy of multi-purpose lens care solutions using the
      FDA's revised guidance document for industry: stand-alone primary criteria.
AB  - PURPOSE: We evaluated six single-bottle, multi-purpose lens care solutions and a
      two component lens care system for disinfection efficacy according to the stand
      alone primary criteria within the recently published U.S. Food and Drug
      Administration (FDA) Guidelines. METHODS: One-tenth mL of 1 x 10(8) colony
      forming units (CFU)/mL of bacterial and fungal challenge organisms was added to
      each test solution. Following a specified period (e.g., each manufacturer's
      labeled minimum disinfection time), aliquots of inoculated test solution were
      neutralized and plated on validated recovery media. After incubation the number
      of viable microorganisms were enumerated and mean log reductions determined.
      RESULTS: ReNu and ReNu MultiPlus met the FDA's acceptance criteria for stand
      alone disinfectants against all challenge organisms: Staphylococcus aureus,
      Serratia marcescens, Pseudomonas aeruginosa, Candida albicans, and Fusarium
      solani. Opti-Free Express failed to meet the FDA's stand-alone disinfectant
      acceptance criteria for S. aureus, S. marcescens and C. albicans and Opti-Free
      Express with Opti-Free Supraclens failed to meet the acceptance criteria for
      either S. aureus and C. albicans. Opti-One failed to meet the FDA's stand-alone
      disinfectant acceptance criteria for C. albicans and F. solani. Both Complete and
      Solo-Care failed to meet the FDA's acceptance criteria for C. albicans.
      CONCLUSIONS: This evaluation provides a direct comparison of antimicrobial
      activity (based on stand-alone criteria) for commercially available multi-purpose
      lens care solutions at their labeled minimum disinfection times. The results of
      this study should be considered when selecting appropriate lens care systems for
      patients.

PMID- 10073639
TI  - Assessment of corneal decompensation in eyes having undergone molteno shunt
      procedures compared to eyes having undergone trabeculectomy.
AB  - PURPOSE: To compare the incidence of corneal decompensation after Molteno shunt
      to trabeculectomy. METHODS: We conducted a retrospective analysis of the corneal
      status of 55 patients with primary open angle glaucoma. We compared 24 eyes of 24
      patients who underwent Molteno tube shunt placement (Group 1) to fifteen eyes of
      14 patients with multiple surgical procedures, including a trabeculectomy (Group
      2). We also compared Group 1 to 28 eyes of 17 patients who underwent only one
      trabeculectomy (Group 3). RESULTS: The three groups were similar with respect to
      age, sex, and intraocular pressure (IOP). The average follow-up time from the
      last surgery in Group 1 was 17.9 months (1-90 months), 22.4 months (2-63 months)
      in Group 2, and 19.6 months (1-37 months) in Group 3. The average number of
      surgeries was 3.0 (1-4) in Group 1 and 2.53 (1-4) in Group 2. The surgeries
      included trabeculectomy, cataract extraction, combined procedures, penetrating
      keratoplasty, pars plana vitrectomy, and scleral buckle. The incidence of corneal
      edema was 50% (12/24)in Group 1, 6.7% (1/15) in Group 2, and 0% in Group 3
      (0/28). The average time to corneal decompensation was 21 months in Group 1 (1
      120 months) and 15 months in Group 2. CONCLUSION: Patients undergoing Molteno
      shunt placement have a higher rate of corneal decompensation compared to patients
      undergoing trabeculectomy.

PMID- 10073640
TI  - Arthur Steindler and orthopaedic research.

PMID- 10073641
TI  - Is collagen fatigue failure a cause of osteoarthrosis and prosthetic component
      migration? A hypothesis.

PMID- 10073642
TI  - Ultrahigh molecular weight polyethylene particles have direct effects on
      proliferation, differentiation, and local factor production of MG63 osteoblast
      like cells.
AB  - Small particles of ultrahigh molecular weight polyethylene stimulate formation of
      foreign-body granulomas and bone resorption. Bone formation may also be affected
      by wear debris. To determine if wear debris directly affects osteoblasts, we
      characterized a commercial preparation of ultrahigh molecular weight polyethylene
      (GUR4150) particles and examined their effect on MG63 osteoblast-like cells. In
      aliquots of the culture medium containing ultrahigh molecular weight
      polyethylene, 79% of the particles were less than 1 microm in diameter,
      indicating that the cells were exposed to particles of less than 1 microm. MG63
      cell response to the particles was measured by assaying cell number,
      [3H]thymidine incorporation, alkaline phosphatase specific activity, osteocalcin
      production, [35S]sulfate incorporation, and production of prostaglandin E2 and
      transforming growth factor-beta. Cell number and [3H]thymidine incorporation were
      increased in a dose-dependent manner. Alkaline phosphatase specific activity, a
      marker of cell differentiation for the cultures, was significantly decreased, but
      osteocalcin production was not affected. [35S]sulfate incorporation, a measure of
      extracellular matrix production, was reduced. Prostaglandin E2 release was
      increased, but transforming growth factor-beta production was decreased in a dose
      dependent manner. This shows that ultrahigh molecular weight polyethylene
      particles affect MG63 proliferation, differentiation, extracellular matrix
      synthesis, and local factor production. These effects were direct and dose
      dependent. The findings suggest that ultrahigh molecular weight polyethylene wear
      debris particles with an average size of approximately 1 microm may inhibit bone
      formation by inhibiting cell differentiation and reducing transforming growth
      factor-beta production and matrix synthesis. In addition, increases in
      prostaglandin E2 production may not only affect osteoblasts by an autocrine
      pathway but may also stimulate the proliferation and activation of cells in the
      monocytic lineage. These changes favor decreased bone formation and increased
      bone resorption as occur in osteolysis.

PMID- 10073643
TI  - Fibroblast distribution in the anteromedial bundle of the human anterior cruciate
      ligament: the presence of alpha-smooth muscle actin-positive cells.
AB  - The anterior cruciate ligament is a complex tissue composed of structural
      proteins, proteoglycans, and cells. The histology of the human anterior cruciate
      ligament is characterized by the specific distribution and density of the
      fibroblast phenotype as well as by the unique organization of the structural
      proteins. A notable finding of this study was the identification of three
      histologically different zones along the anteromedial bundle as it coursed from
      the femoral to the tibial attachment. Two of the zones, the fusiform and ovoid,
      were located in the proximal one-quarter of the bundle; the third zone, the
      spheroid, occupied the distal three quarters of the bundle fascicles. The
      fusiform cell zone was characterized by a high number density of longitudinally
      oriented cells with a fusiform-shaped nucleus, longitudinal blood vessels, and
      high crimp length. The cytoplasm of the cells in this zone appeared to be
      intimately attached to the extracellular collagen and followed the crimp waveform
      of the fibers. Fusiform cells were noted to stain positively for the alpha-smooth
      muscle actin isoform in this region, particularly at areas of crimp disruption.
      The ovoid cell zone was characterized by a high number density of cells with an
      ovoid-shaped nucleus, longitudinal vessels, and a high crimp length. In this zone
      as well, the cytoplasm of the cells appeared to follow the waveform of the
      adjacent collagen. Ovoid cells were noted to stain positively for the alpha
      smooth muscle actin isoform in this region. The spheroid cell zone was
      characterized by a low density of spheroid cells, few blood vessels, and short
      crimp length. Cells were noted within and among fascicles, as well as within
      lacunae. In selected areas, as many as 50% of the cells in this region stained
      positively for the alpha-smooth muscle actin isoform. This is also the first
      report of cells expressing the alpha-smooth muscle actin isoform in the intact
      human anterior cruciate ligament. This specific type of contractile actin,
      initially identified only in smooth-muscle cells, pericytes, and myofibroblasts,
      was seen in cells with various morphologies and predominantly in cells located at
      areas of crimp disruption. Further work is necessary to elucidate the role of the
      various fibroblast phenotypes in the maintenance of the human anterior cruciate
      ligament.

PMID- 10073644
TI  - Patellar tendon augmentation after removal of its central third limits joints
      tissue changes.
AB  - The central third of the patellar tendon is commonly used to reconstruct the
      injured anterior cruciate ligament. Some studies have noted changes in joint
      tissues following this procedure. It has been postulated that these changes may
      be associated with increased stress on the remaining tendon following harvest of
      the graft. In our study, the central third of the patellar tendon was excised in
      three groups of rabbits. The central tendon defects in two of the three groups
      were fitted with different augmentation devices to augment the host tendon during
      the healing process. All rabbits followed a daily treadmill exercise regimen for
      12 weeks following the operation. Biomechanical testing of the tendon revealed
      that in nonaugmented tendons the cross-sectional area and the length of the
      patellar tendon significantly increased 112 and 16%, respectively. There was
      histological evidence of host-tendon remodeling throughout the cross section and
      extensive fibrosis in the infrapatellar fat pad. Augmentation of the tendon
      significantly reduced these changes, with the least change noted in the group
      with the greatest augmentation. The rabbits with augmentation devices retained
      tendon dimensions similar to those of the contralateral intact tendon, and tendon
      remodeling occurred only in the defect area. The rabbits with augmentation
      devices exhibited little to no fibrosis of the fat pad. Structural properties of
      augmented and nonaugmented tendons were similar despite the size differences,
      indicating higher tissue quality in the augmented tendons. This study suggested
      that complications of the knee joint (i.e., tendon proliferation and fat pad
      fibrosis) noted after anterior cruciate-ligament reconstruction with the
      autogenous patellar tendon may be limited by the implantation of an augmentation
      device.

PMID- 10073645
TI  - Early expression of marker genes in the rabbit medial collateral and anterior
      cruciate ligaments: the use of different viral vectors and the effects of injury.
AB  - Gene therapy is a technique that may offer advantages over current methods of
      cytokine delivery to ligaments. To determine if implanted genes could be
      expressed in normal and injured knee ligaments, the medial collateral ligament
      and anterior cruciate ligament were studied in 18 rabbits. A retroviral ex vivo
      technique using allograft medial collateral ligament and anterior cruciate
      ligament fibroblasts and an adenoviral in vivo technique were compared as methods
      for delivering the LacZ marker gene to knee ligaments. Bilateral knee surgeries
      were performed, and the rabbits were equally divided into three groups. Group 1
      received the retrovirus and the medial collateral ligament was ruptured, Group 2
      received the adenovirus and the medial collateral ligament was ruptured, and
      Group 3 received the adenovirus and the medial collateral ligament was not
      injured. The anterior cruciate ligament was not injured in any group. The medial
      collateral and anterior cruciate ligaments of the right knees received 10(6)
      allografted, transduced ligament fibroblasts or 10(9) adenovirus particles,
      whereas the ligaments of the left knee received a similar volume of saline
      solution only. Equal numbers of rabbits were killed at 10 days, 3 weeks, and 6
      weeks following the procedure. Ligament samples were stained with X-gal to detect
      the expression of the LacZ gene product, beta-galactosidase. LacZ gene expression
      was evident in ruptured and uninjured medial collateral ligaments as well as in
      the anterior cruciate ligament. The expression lasted between 10 days and 3 weeks
      in the medial collateral and anterior cruciate ligaments with use of the
      retrovirus and between 3 and 6 weeks in the medial collateral ligament and at
      least 6 weeks in the anterior cruciate ligament with the adenovirus. The length
      of gene expression in the ruptured and uninjured medial collateral ligaments did
      not differ. These preliminary studies indicate that gene transfer to normal and
      injured knee ligaments is possible.

PMID- 10073646
TI  - Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene
      transfer induces mesenchymal progenitor cell proliferation and differentiation in
      vitro and bone formation in vivo.
AB  - This study reports that recombinant adenovirus-mediated human bone morphogenetic
      protein-2 gene transfer can induce mesenchymal progenitor cell differentiation
      and bone formation. The recombinant adenovirus with the human bone morphogenetic
      protein-2 gene was constructed, and mature human bone morphogenetic protein-2
      expression mediated by adenovirus gene transfer was detected by specific
      antibody. Under adenovirus-mediated bone morphogenetic-protein gene transfer,
      mesenchymal progenitor cell line C3H/10T 1/2 showed cell proliferation dependent
      on adenovirus bone morphogenetic-protein dose. The C3H/10T 1/2 cells transduced
      by adenovirus bone morphogenetic protein also exhibited differentiation to
      osteoblast phenotype, which indicates alkaline phosphatase activity. Injection of
      the C3H/10T 1/2 cells into the thigh muscles of nude mice led to ossicle
      development detectable on radiographs. Histological analysis indicated that the
      new ossicles that developed in the thigh muscles of the mice had different
      osseous components including bone trabeculae, bone marrow, and chondrified
      tissue. The results of this study demonstrate the potential for gene therapy by
      adenovirus-mediated bone morphogenetic-protein gene transfer.

PMID- 10073647
TI  - Bone marrow cells produce soluble factors that inhibit osteoclast activity.
AB  - Cytokines that stimulate bone resorption are produced by cells found in bone
      marrow. However, marrow cells produce multiple factors, some of which may be
      inhibitors of osteoclast differentiation or activity. Thus, it is not possible to
      predict a priori whether the mixture of factors produced by marrow cells will
      have a net stimulatory or inhibitory effect on bone resorption. In this study, we
      showed that the net effect of whole marrow is to inhibit osteoclast activity
      induced by parathyroid hormone. Fractionation of the marrow revealed that the
      inhibitory activity was in the marrow fluid. However, conditioned media obtained
      from marrow cell cultures also inhibited osteoclast activity. Thus, it is likely
      that the inhibitory factors are produced in vivo by cells residing in the marrow.
      These inhibitory factors may represent a physiological regulatory process that
      plays an important role in maintaining the balance between bone resorption and
      formation. Because we have previously shown that interleukin-6 is one of the
      cytokines that parathyroid hormone induces in osteoblastic cells to stimulate
      osteoclast activity, one potential mechanism by which the marrow-derived
      inhibitory factors might act is by preventing this production of interleukin-6.
      However, we found that the marrow cell-conditioned media do not inhibit the
      production or activity of interleukin-6. Thus, the inhibitory factors appear to
      block osteoclast activity through a mechanism that does not involve interleukin
      6. Taken together, these results demonstrate the importance of factors that
      inhibit bone resorption and emphasize that the presence of cytokines that
      stimulate bone resorption in conditions such as osteoporosis and orthopaedic
      implant loosening should be interpreted with caution unless evidence exists
      demonstrating their functional importance.

PMID- 10073648
TI  - Elastic anisotropy and collagen orientation of osteonal bone are dependent on the
      mechanical strain distribution.
AB  - There is evidence that the collagen microarchitecture of bone is influenced by
      mechanical stresses or strains. We hypothesized that peak functional strains
      correlate with the elastic anisotropy and collagen orientation of bone tissue and
      that the bone anisotropy might be changed by altering the strain patterns in
      canine radii for 12 months. We tested these hypotheses in studies using nine
      adult foxhounds. The baseline group (n = 3) had three rosette strain gauges
      placed around the midshaft of the radius, and strain distributions were measured
      during walking. The osteotomy group (n = 3) had 2 cm of the ulna surgically
      removed, and the sham group (n = 3) received a sham osteotomy. The osteotomy and
      sham groups were allowed free movement in cages with runs for 12 months, after
      which strain distributions were measured on the radii during walking. Bone-tissue
      anisotropy and collagen architecture were measured in radii from which the in
      vivo longitudinal strain patterns had been measured. The collagen birefringence
      patterns were measured with use of a circularly polarized light technique, and
      the elastic anisotropy of the bone, mineral, and collagen matrix was evaluated
      with a novel acoustic microscopy technique. Peak longitudinal strains in the
      radius correlated with the normalized longitudinal structure index (a polarized
      light measure of collagen birefringence) and the tissue anisotropy ratio. The
      average anisotropy ratio was 1.28+/-0.01 in the posterior (compressive) cortex
      and 1.43+/-0.01 in the anterior (tensile) cortex (these values are significantly
      different at p < 0.0001). The ulnar osteotomy changed the strain pattern on the
      radius, causing increased tensile strains in the medial cortex by more than 5
      fold that were associated with a significant increase in the anisotropy ratio in
      the bone tissue. The longitudinal structure index was strongly correlated (r =
      0.62, p < 0.005) with the anisotropy ratio of demineralized bone but was not
      correlated with that of deproteinized bone; this indicates that it reflects
      collagen fibril orientation in the bone matrix. These results indicate that
      mechanical strains affect both collagen and mineral microarchitecture in bone
      tissue, i.e., tensile strains are associated with increased tissue anisotropy and
      compressive strains, with decreased anisotropy.

PMID- 10073649
TI  - Intravertebral body reconstruction with an injectable in situ-setting carbonated
      apatite: biomechanical evaluation of a minimally invasive technique.
AB  - The ability to mechanically reinforce an osteoporotic vertebral body could impede
      spinal compression fracture and the associated pain and complications. Previous
      studies have shown that reinforcement of fractured vertebrae with conventional
      acrylic cement can relieve symptoms and avoid further collapse. In this study, we
      explored the use of a carbonated apatite cement combined with a minimally
      invasive injection technique to improve the compressive mechanical properties of
      cadaveric vertebral bodies. After establishing the biomechanical characteristics
      of cement formulations intended to have appropriate viscosities, we evaluated the
      infiltration of the cements into thoracic vertebral bodies using a combined
      suction-injection technique. The energy-absorption capabilities of the reinforced
      vertebral bodies were then measured during axial compressive tests and compared
      with those of nonreinforced vertebrae. The ultimate compressive strength of the
      cement formulations averaged from 11.6 to 17.7 MPa, depending on curing
      conditions. The suction-injection technique allowed from one-half to two-thirds
      of each vertebral body to be infiltrated with cement. Energy absorption was
      significantly higher (p < 0.05) between 25 and 70% collapse of the vertebral body
      in the specimens that received the apatite injection as compared with the
      controls. These results suggest that osteoporotic vertebral-body augmentation
      with the injection of apatite cement could prevent further collapse after initial
      failure has occurred. The osteoconductive nature of the cement and its ability to
      be remodeled by bone, together with its compressive strength, which is higher
      than that of cancellous bone, could provide better clinical results than those of
      current treatments with acrylic cement.

PMID- 10073650
TI  - Growth potential of loose bodies: an immunohistochemical examination of primary
      and secondary synovial osteochondromatosis.
AB  - Histologic and immunohistochemical studies of growth potential were performed on
      53 surgically removed loose bodies representing 10 cases of primary synovial
      osteochondromatosis, 37 bodies representing 12 cases of secondary synovial
      osteochondromatosis, and five bodies representing five cases of osteochondral
      fracture. Loose bodies in primary synovial osteochondromatosis were nodular,
      showing plump chondrocytes and irregular calcification, and all contained
      proliferative cell nuclear antigen-positive chondrocytes (labeling index: 42.5%;
      range: 36.0-52.0%). Other markers stained less frequently. Loose bodies in
      secondary synovial osteochondromatosis showed uniform chondrocytes and annular
      calcification surrounding core tissue. Eighteen of 37 loose bodies showed
      proliferative cell nuclear antigen-positive chondrocytes, mostly peripherally.
      Chondrocyte labeling indices were less than 5% for proliferative cell nuclear
      antigen and other markers, although some connective tissue cells in the outer
      layer were stained. Loose bodies from osteochondral fractures were composed of
      articular cartilage, subchondral bone, and connective tissue; cartilage was
      negative for markers, whereas connective tissue contained positive cells. One
      specimen showed cartilaginous metaplasia of connective tissue. These results
      suggest that loose bodies have the potential for slow growth by proliferation of
      chondrocytes in primary synovial osteochondromatosis and by metaplasia following
      proliferation of surrounding connective tissue in secondary synovial
      osteochondromatosis.

PMID- 10073651
TI  - Evaluation of blood flow within the subchondral bone of the femoral head: use of
      the laser speckle method at surgery for osteonecrosis.
AB  - The laser speckle method is a new form of tissue flowmetry that can analyze the
      interference pattern that appears when tissue is illuminated with a laser beam.
      During surgery for 100 cases of osteonecrosis of the femoral head, we measured
      the blood flow within the subchondral bone using this method. We compared the
      flow maps (two-dimensional distribution of the microcirculation) obtained this
      way with the necrotic area estimated by the preoperative magnetic resonance
      images and with the collapse seen during surgery. The laser speckle method was
      able to distinguish between the ischemic areas and the normal areas in 92 femoral
      heads, including five hips for which neither the magnetic resonance images nor
      the collapse observed during surgery demonstrated a distinct margin surrounding
      the necrotic area. We concluded that the laser speckle method is useful for
      defining the margin around a necrotic area.

PMID- 10073652
TI  - Intermittent pneumatic compression of legs increases microcirculation in distant
      skeletal muscle.
AB  - Intermittent pneumatic compression has been established as a method of clinically
      preventing deep vein thrombosis, but the mechanism has not been documented. This
      study observed the effects of intermittent pneumatic compression of legs on the
      microcirculation of distant skeletal muscle. The cremaster muscles of 80 male
      rats were exposed, a specially designed intermittent pneumatic-compression device
      was applied to both legs for 60 minutes, and the microcirculation of the muscles
      was assessed by measurement of the vessel diameter in three categories (10-20, 21
      40, and 41-70 microm) for 120 minutes. The results showed significant
      vasodilation in arterial and venous vessels during the application of
      intermittent pneumatic compression, which disappeared after termination of the
      compression. The vasodilation reached a maximum 30 minutes after initiation of
      the compression and could be completely blocked by an inhibitor of nitric oxide
      synthase, NG-monomethyl-L-arginine (10 micromol/min). A 120-minute infusion of NG
      monomethyl-L-arginine, beginning coincident with 60 minutes of intermittent
      pneumatic compression, resulted in a significant decrease in arterial diameter
      that remained at almost the same level after termination of the compression. The
      magnitude of the decrease in diameter in the group treated with intermittent
      pneumatic compression and NG-monomethyl-L-arginine was comparable with that in
      the group treated with NG-monomethyl-L-arginine alone. The results imply that the
      production of nitric oxide is involved in the positive influence of intermittent
      pneumatic compression on circulation. It is postulated that the rapid increase in
      venous velocity induced by intermittent pneumatic compression produces strong
      shear stress on the vascular endothelium, which stimulates an increased release
      of nitric oxide and thereby causes systemic vasodilation.

PMID- 10073653
TI  - Noninvasive technique for measuring in vivo three-dimensional carpal bone
      kinematics.
AB  - Our present knowledge of the three-dimensional kinematic behavior of skeletal
      joints has been largely acquired with cadaveric models and use of invasive
      monitoring. In the wrist, the small size and complex motion of the carpal bones
      present a difficult challenge for implanted internal or external marker systems.
      This paper describes a technique for quantifying the three-dimensional kinematics
      of the wrist and carpal bones in vivo using noninvasive computed tomographic
      imaging. An error analysis employing a cadaveric specimen suggests that
      noninvasive carpal kinematics can be measured with an accuracy within 2 degrees
      of rotation and 1 mm of translation along a helical axis of motion. The in vivo
      application of this technique is illustrated with a single normal individual.
      Potential applications include the quantification of normal wrist motion,
      analysis of pathomechanics, and evaluation of surgical intervention. The
      technique is also applicable to other joints and imaging modalities.

PMID- 10073654
TI  - Musculoskeletal function assessment: reference values for patient and non-patient
      samples.
AB  - Although researchers and clinicians are encouraged to use health-status
      questionnaires to evaluate, monitor, and modify care, their use is hindered by
      the lack of reference values. Without reference values, it is difficult to
      interpret or evaluate questionnaire scores. In this paper, we present reference
      values for the Musculoskeletal Function Assessment, a 101-item health-status
      questionnaire designed and validated for patients with a broad range of
      musculoskeletal disorders. We describe reference values for two samples: non
      patients (n = 123) and patients with isolated extremity injuries (n = 274). For
      the non-patient sample, descriptive statistics are presented by age and gender,
      measured at one point in time. For the patient sample, descriptive statistics are
      provided for seven Orthopaedic Trauma Association/AO diagnostic groups, measured
      at two points in time. Reference values for changes in the Musculoskeletal
      Function Assessment total score are described for patients 3 and 9 months and 6
      and 12 months after injury. The total scores by post-injury interval, across the
      diagnostic groups, are significantly better at follow-up than at baseline (p =
      0.00). Reference values for changes in total scores are also described in terms
      of these diagnostic groups across post-injury intervals. Musculoskeletal Function
      Assessment total scores for Orthopaedic Trauma Association/AO diagnostic groups
      are significantly better at follow-up than at baseline (p < 0.03). Changes in the
      total score are also tested for responsiveness with use of standardized response
      means. Large effects are demonstrated for patients completing the Musculoskeletal
      Function Assessment at 3 and 9 months (1.03), and small effects are demonstrated
      for those completing it at 6 and 12 months (0.49). Moderate and large effects are
      demonstrated for Orthopaedic Trauma Association/AO diagnostic groups across post
      injury intervals.

PMID- 10073655
TI  - Immunodetection and partial cDNA sequence of the proteoglycan, superficial zone
      protein, synthesized by cells lining synovial joints.
AB  - We have previously described a large proteoglycan named superficial zone protein
      that was isolated and purified from culture medium of superficial slices of
      bovine articular cartilage. Monoclonal antibodies were raised against superficial
      zone protein and used as probes in Western blot analyses for immunohistochemical
      studies both to determine precisely which cells within the joint synthesize the
      proteoglycan and to isolate a cDNA fragment from a bovine chondrocyte lambdagt11
      library that encodes part of the proteoglycan. The cDNA fragment that was
      obtained with use of monoclonal antibody 6-A-1 encodes the 3' end of the sequence
      for superficial zone protein. On Western blots, monoclonal antibody 3-A-4
      recognized an epitope on native, but not reduced, superficial zone protein,
      whereas monoclonal antibody 6-A-1 reacted with both native and denatured antigen.
      The proteoglycan was immunolocalized with monoclonal antibody 3-A-4 in
      chondrocytes predominantly within the superficial zone of fetal and adult
      articular cartilage and in some cells of the synovial lining. However, the
      proteoglycan was not detected in chondrocytes deep in articular cartilage, in
      nasal septal cartilage, or in synovial stromal cells. The only matrix staining
      positively for superficial zone protein was at the articular surface bordering
      the synovial cavity in adult, but not fetal, joints. Isolated chondrocytes and
      synovial cells showed intracellular binding of monoclonal antibody 3-A-4, and
      flow-cytometric analysis with the antibody gave the following percentages of
      immunopositive cells: 37.4, 52.5, 3.4, and 7.5 from chondrocytes from the full
      thickness, superficial, and deep zones and from synovial cells, respectively.
      Thus, both chondrocytes and synovial cells bordering the joint cavity synthesize
      superficial zone protein and substantiate its usefulness as a phenotypic marker
      of particular cellular species lining the articular cavity.

PMID- 10073656
TI  - Effect of seeding duration on the strength of chondrocyte adhesion to articular
      cartilage.
AB  - Chondrocyte adhesion to cartilage may play an important role in the repair of
      articular defects by maintaining cells in positions where their biosynthetic
      products can contribute to the repair process. The objective of this in vitro
      study was to determine the effect of the duration of seeding time on the ability
      of chondrocytes to resist detachment from cartilage when subjected to mechanical
      perturbation (fluid-induced shear stress). Suspensions of adult bovine articular
      chondrocytes were prepared from primary, high-density monolayer cultures and
      infused into a parallel-plate shear-flow chamber where they settled onto 50
      microm-thick sections of bovine articular cartilage at a density of approximately
      20,000 cells/cm2. The chondrocytes were seeded and allowed to attach to the
      cartilage surface for specific durations (5-40 minutes) in medium including 10%
      serum at 22 degrees C, after which the cells were exposed to fluid flow-induced
      shear stresses (6-90 Pa). The fraction of detached cells at each shear stress was
      calculated from microscopic images. Shear stress was applied for 1 minute because
      this length of time was sufficient to induce steady-state cell detachment.
      Increasing the duration of cell seeding led to a more firm attachment of
      chondrocytes to cartilage. After 9 minutes of seeding, 50% cell detachment was
      induced by gravitational force alone. After 40 minutes of seeding, 50% detachment
      required 26 Pa of shear stress. Extrapolation of the data to account for the
      effect of repeated applications of cell suspensions to an individual cartilage
      substrate indicated that for a freshly prepared cartilage section, 50% detachment
      was induced by gravity after 25 minutes of seeding and by 2.3 Pa of shear stress
      after 40 minutes of seeding. The increase in resistance to shear stress-induced
      cell detachment with increasing seeding duration suggests that it may be
      beneficial to allow chondrocytes to stabilize in the absence of applied load for
      some time after chondrocyte transplantation for cartilage repair in vivo.

PMID- 10073657
TI  - Bioreactor cultivation conditions modulate the composition and mechanical
      properties of tissue-engineered cartilage.
AB  - Cartilaginous constructs have been grown in vitro with use of isolated cells,
      biodegradable polymer scaffolds, and bioreactors. In the present work, the
      relationships between the composition and mechanical properties of engineered
      cartilage constructs were studied by culturing bovine calf articular chondrocytes
      on fibrous polyglycolic acid scaffolds (5 mm in diameter, 2-mm thick, and 97%
      porous) in three different environments: static flasks, mixed flasks, and
      rotating vessels. After 6 weeks of cultivation, the composition, morphology, and
      mechanical function of the constructs in radially confined static and dynamic
      compression all depended on the conditions of in vitro cultivation. Static
      culture yielded small and fragile constructs, while turbulent flow in mixed
      flasks yielded constructs with fibrous outer capsules; both environments resulted
      in constructs with poor mechanical properties. The constructs that were cultured
      freely suspended in a dynamic laminar flow field in rotating vessels were the
      largest, contained continuous cartilage-like extracellular matrices with the
      highest fractions of glycosaminoglycan and collagen, and had the best mechanical
      properties. The equilibrium modulus, hydraulic permeability, dynamic stiffness,
      and streaming potential correlated with the wet-weight fractions of
      glycosaminoglycan, collagen, and water. These findings suggest that the
      hydrodynamic conditions in tissue-culture bioreactors can modulate the
      composition, morphology, mechanical properties, and electromechanical function of
      engineered cartilage.

PMID- 10073658
TI  - In situ expression of collagen and proteoglycan genes during development of
      fibrocartilage in bovine deep flexor tendon.
AB  - A region of fibrocartilage develops in bovine deep flexor tendon where the tissue
      wraps around bone and is subjected to compressive and shear forces in addition to
      tension. There is no fibrocartilage at this location in fetal tendon or in
      adjacent adult tendon that is subjected to tensional load only. We investigated
      the development of fibrocartilage in tendon using in situ hybridization to
      localize cells that express collagen and proteoglycan genes typical of either
      tendon or cartilage. The signal for type I collagen and decorin was high in cells
      throughout fetal and newborn tendon, as is expected in a growing tissue composed
      predominantly of type I collagen. No signal for aggrecan was seen in either fetal
      or newborn tendon. No hybridization with any of the probes for collagen or
      proteoglycan was detected in cells in the tensional region of adult tendon,
      indicating that the cells in this tissue are normally quiescent. However, the
      cells in the fibrocartilage of adult tendon displayed a high level of expression
      for types I and II collagen, decorin, biglycan, and aggrecan. This suggests that
      the fibrocartilage in adult tendon is a dynamic tissue. Expression of type IIA
      collagen is considered a marker of prechondrocytes. Type IIA collagen gene
      expression was present throughout both the tensional and compressed regions of
      fetal and newborn tendon but was absent in cartilage and adult tendon. This
      suggests that cells located throughout fetal tendon may have the capacity to
      develop as chondrocytes. Fibrocartilage signal was detected for type I collagen
      in 75% of the cells and for type II collagen in 50% of the cells at one location
      in adult tendon, suggesting that some cells in this tissue could have expressed
      mRNA for both type I and type II collagen.

PMID- 10073659
TI  - Fracture-healing model in the rat.

PMID- 10073660
TI  - Performance of silicon microdosimetry detectors in boron neutron capture therapy.
AB  - Reverse-biased silicon p-n junction arrays using Silicon-On-Insulator technology
      have been proposed as microdosimeters. The performance of such detectors in boron
      neutron capture therapy (BNCT) is discussed. This work provides the first
      reported measurements using boron-coated silicon diode arrays as microdosimeters
      in BNCT. Results are in good agreement with measurements with gas proportional
      counters. Various boron-coating options are investigated along with device
      orientation effects. Finally, a 235U coating is tested to simulate the behavior
      of the device in a heavy-ion therapy beam.

PMID- 10073661
TI  - Radiotoxicity of bismuth-213 bound to membranes of monolayer and spheroid
      cultures of tumor cells.
AB  - Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle
      emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on
      kinetics and saturation of binding, cell shape and nuclear size were used to
      calculate the absorbed dose to the nuclei. Treatment of monolayer cells with
      [213Bi]MAb 13A produced a classical exponential survival curve with no apparent
      shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37%
      surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb
      13A mainly on the outer cell layer. Relatively small amounts of activity added to
      the spheroids resulted in relatively large absorbed doses. The result was that 3
      6-fold less added radioisotope was necessary to kill similar fractions of cells
      in spheroids than in monolayer cells. These data are consistent with the
      interpretation that the alpha particles from a single 213Bi atom bound to one
      cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells
      originating from the periphery or from the interior of spheroids. Cells from the
      outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction
      per administered activity than cells from the interior. Cells were killed
      efficiently in spheroids up to 20-30 cells in diameter. The data support the
      hypothesis that alpha-particle emitters should be very efficient at killing cells
      in micrometastases of solid tumors.

PMID- 10073662
TI  - Induced repair of DNA double-strand breaks at the G1/S-phase border.
AB  - Exposure of human cells to ionizing radiation at the G1/S-phase border of the
      cell cycle leads to the production of repair patches of 3 nucleotides,
      representing the constitutive repair response, and very long repair patches
      (VLRP) of at least 150 nucleotides, representing an induced response. We examined
      the type of DNA damage that may signal this induced repair response using two
      chemicals that produce subsets of the damage induced by ionizing radiation.
      Treatment of cells at the G1/S-phase border with bleomycin, which produces a high
      proportion of DNA double-strand breaks, also leads to the production of VLRP of
      at least 130 nucleotides. In contrast, when cells were treated with hydrogen
      peroxide, which produces base modifications and single-strand breaks, no VLRP
      were observed. Thus it would appear that DNA double-strand breaks are the signal
      that leads to the induction of the VLRP. We also examined the relationship
      between the induced repair response and DNA replication. When cells are treated
      with hydroxyurea, under conditions that inhibit more than 98% of the DNA
      synthesis, prior to exposure to 5 Gy, repair patches of 3 and 150 nucleotides are
      found. This indicates that the longer repair patches are not a result of aberrant
      DNA replication. However, when cells are treated with the DNA polymerase
      inhibitor aphidicolin in combination with hydroxyurea and cytosine arabinoside,
      no induced long patches are found. These results indicate that DNA polymerase
      alpha, delta or epsilon is required for the synthesis of the VLRP.

PMID- 10073663
TI  - TP53 is not required for the constitutive or induced repair of DNA damage
      produced by ionizing radiation at the G1/S-phase border.
AB  - We have previously described a novel DNA repair response that is induced in cells
      irradiated with ionizing radiation at the G1/S-phase border and is characterized
      by the formation of very long repair patches (VLRP) containing at least 150
      nucleotides. In the current study, we examined whether there is a requirement for
      TP53 in this induced repair process. We find that in normal cells, the endogenous
      levels of TP53 are elevated at the G1/S-phase border, and that these levels are
      not further increased after irradiation with 5 Gy. In cells expressing the E6
      oncoprotein of human papillomavirus, which inactivates TP53 function, there is a
      greatly accentuated induction of the VLRP that nearly masks the constitutive
      repair response. Incubation of cells in the presence of cycloheximide, which
      inhibits the induced repair, reveals the presence of the constitutive repair
      patches. All cells examined continue to replicate their DNA after exposure to
      ionizing radiation. In contrast, cells irradiated with UV radiation at the G1/S
      phase border show an induction of TP53 protein and halt DNA synthesis, but do not
      induce the VLRP. Our results show that TP53 is not required for the constitutive
      or induced repair of DNA damage induced by ionizing radiation. In addition, these
      results suggest that TP53 may suppress the formation of VLRP and that the
      progression of cells through S phase after exposure to ionizing radiation signals
      the induced repair response.

PMID- 10073664
TI  - Early effects of ionizing radiation on the microvascular networks in normal
      tissue.
AB  - Microvascular networks, which control the delivery of oxygen and nutrients and
      the removal of metabolic waste, are the most sensitive part of the vascular
      system to ionizing radiation. Structural and functional changes in microvascular
      networks were studied in locally irradiated (single 10-Gy dose) hamster cremaster
      muscles observed 3, 7 and 30 days post-irradiation. Networks were selected in
      reference to a well-defined location in the tissue to reduce heterogeneity due to
      spatial variations. Intravital microscopy was used to measure structural and
      functional parameters in vivo. A factorial design was used to examine the effects
      of radiation status, time postirradiation, and network vessel type on the
      structure and function of microvascular networks. While the diameter of
      microvessels in control animals increased significantly with age, vessel diameter
      in irradiated vessels decreased significantly with age. Red blood cell velocity
      in irradiated networks at 3 and 30 days postirradiation was significantly lower
      than in control networks. There was a significant decrease in capillary surface
      area and a significant increase in vessel hematocrit in irradiated animals. Blood
      flow in irradiated vessels was significantly lower than in control vessels.
      Changes in functional parameters were evident at 3 days postirradiation while
      changes in structural parameters occurred later. All vessel types were not
      damaged equally by radiation at every time examined.

PMID- 10073665
TI  - TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible.
AB  - The objective of this study was to investigate the incidence of overexpression of
      TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit
      mandibles with high-dose external-beam radiation. As part of a protocol
      investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New
      Zealand-White rabbits underwent mandibular radiation treatments with a total dose
      of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation,
      leaving 90 animals at risk for tumor development. These animals were divided into
      one control group and 12 other groups each treated with different schedules of
      postirradiation hyperbaric oxygen. All animals were sacrificed after the
      hyperbaric oxygen treatment, approximately 8 months after completion of
      irradiation. Seventeen of the 90 animals that survived after irradiation
      developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor
      sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected
      a 59% overall incidence of TP53 overexpression. There was no correlation between
      the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The
      high incidence and short interval of development of osteosarcoma suggest that the
      study animals may have had a genetic predisposition to radiation-induced
      osteosarcoma. Additionally, our data provide further evidence that TP53 mutations
      may play an important role in radiation-induced osteosarcoma.

PMID- 10073666
TI  - Activation of heat-shock transcription factor 1 in heated Chinese hamster ovary
      cells is dependent on the cell cycle and is inhibited by sodium vanadate.
AB  - Inducible heat-shock protein 70 (HSP72) is expressed in a cell cycle-specific
      manner in Chinese hamster ovary (CHO) cells after heating for 15 min at 45.0
      degrees C, with the highest level in S-phase cells. Since heat shock induces the
      transcription of heat-shock proteins through the transactivation of heat-shock
      elements (HSEs) by heat-shock factor HSF1, we wished to determine whether the
      cell cycle-specific expression of HSP72 was regulated at the level of
      transcription. The levels of HSF1 did not vary through the cell cycle, as
      measured by polyclonal antibodies and flow cytometry. The binding of HSF1 to the
      heat-shock element was measured with the gel mobility shift assay using cell
      extracts from Hoechst 33342-labeled heated cells sorted from G1, S and G2/M
      phases. The HSF1-HSE binding activity was twofold higher in S phase than in G1 or
      G2/M phase. When CHO cells were exposed to 10 microM sodium vanadate, an
      inhibitor of tyrosine phosphatase, for 24 h before heat shock, the binding of
      HSF1 to HSE was reduced by a factor of 2 and the level of HSP72 was greatly
      reduced. The HSF1 binding to HSE was completely eliminated by using anti-HSF1
      antibody in the gel mobility shift assays. Antibodies against HSP73 did not
      reduce the HSF1-HSE binding activity, but antibodies against HSP40 actually
      increased the binding activity. These results support the hypothesis that cell
      cycle-dependent binding of HSF1 to HSE is the cause of the cell cycle-specific
      expression of HSP72 in heated CHO cells and is regulated by phosphorylation.

PMID- 10073667
TI  - Mortality after long-term exposure to radioactive Thorotrast: a forty-year follow
      up survey in Sweden.
AB  - To evaluate temporal patterns of cause-specific mortality after long-term
      exposure to the alpha-particle-emitting contrast medium Thorotrast, we
      investigated a cohort consisting of 693 Swedish patients with neurological
      disorders who received Thorotrast during cerebral angiography, with follow-up
      ending in 1993. Standardized mortality ratios (SMRs) were calculated as the ratio
      of observed cases in the cohort to expected cases in the general population.
      Persons exposed to Thorotrast had significant excesses of all causes of death
      (SMR = 2.8; 95% CI 2.5-3.0), with similar increases noted for men and women. The
      largest risks were observed for deaths from hematological causes (SMR = 16.4; n =
      8), cerebrovascular diseases (SMR = 10.1; n = 18), gastrointestinal disorders
      including liver cirrhosis (SMR = 5.2; n = 36), and tumors (SMR = 4.7; n = 187).
      There was a significant decrease in SMR with time since injection for
      cerebrovascular and circulatory diseases, indicative of the impact of underlying
      neurological disorders. In contrast, the SMR increased significantly with time
      for tumors and gastrointestinal diseases, suggestive of a detrimental effect of
      cumulative radiation dose. A significant dose-response relationship was found for
      all causes of death and malignant tumors among all age groups, and since SMR
      increased with time for the latter category, this is consistent with an effect of
      cumulative radiation exposure on cancer development. However, the findings should
      be treated with caution, since selection bias may have influenced some of the
      results.

PMID- 10073668
TI  - Proto-oncogene mRNA levels and activities of multiple transcription factors in
      C3H 10T 1/2 murine embryonic fibroblasts exposed to 835.62 and 847.74 MHz
      cellular phone communication frequency radiation.
AB  - This study was designed to determine whether two differently modulated
      radiofrequencies of the type generally used in cellular phone communications
      could elicit a general stress response in a biological system. The two
      modulations and frequencies studied were a frequency-modulated continuous wave
      (FMCW) with a carrier frequency of 835.62 MHz and a code division multiple-access
      (CDMA) modulation centered on 847.74 MHz. Changes in proto-oncogene expression,
      determined by measuring Fos, Jun, and Myc mRNA levels as well as by the DNA
      binding activity of the AP1, AP2 and NF-kappaB transcription factors, were used
      as indicators of a general stress response. The effect of radiofrequency exposure
      on proto-oncogene expression was assessed (1) in exponentially growing C3H 10T
      1/2 mouse embryo fibroblasts during their transition to plateau phase and (2)
      during transition of serum-deprived cells to the proliferation cycle after serum
      stimulation. Exposure of serum-deprived cells to 835.62 MHz FMCW or 847.74 MHz
      CDMA microwaves (at an average specific absorption rate, SAR, of 0.6 W/kg) did
      not significantly change the kinetics of proto-oncogene expression after serum
      stimulation. Similarly, these exposures did not affect either the Jun and Myc
      mRNA levels or the DNA-binding activity of AP1, AP2 and NF-kappaB in exponential
      cells during transit to plateau-phase growth. Therefore, these results suggest
      that the radiofrequency exposure is unlikely to elicit a general stress response
      in cells of this cell line under these conditions. However, statistically
      significant increases (approximately 2-fold, P = 0.001) in Fos mRNA levels were
      detected in exponential cells in transit to the plateau phase and in plateau
      phase cells exposed to 835.62 MHz FMCW microwaves. For 847.74 MHz CDMA exposure,
      the increase was 1.4-fold (P = 0.04). This increase in Fos expression suggests
      that expression of specific genes could be affected by radiofrequency exposure.

PMID- 10073669
TI  - NF-kappaB or AP-1-dependent reporter gene expression is not altered in human U937
      cells exposed to power-line frequency magnetic fields.
AB  - A number of studies have reported that human leukemia cells respond to exposure
      to power-line frequency electromagnetic fields (EMFs), providing evidence for an
      EMF-induced signaling pathway involving activation of protein tyrosine kinases
      (PTKs), phospholipase-Cy and protein kinase C (PKC). Because activation of PKC is
      also important in the signaling pathways that regulate the transcription factors
      NF-kappaB and AP-1, we evaluated the effect of exposure to a 60 Hz EMF on NF
      kappaB or AP-1-dependent reporter gene expression in cells of the human
      promonocytic U937 leukemia cell line. Reporter genes were electroporated into
      U937 cells and activation of the NF-kappaB or AP-1 signaling pathway was
      evaluated by measuring chloramphenicol acetyltransferase (CAT) protein by CAT
      ELISA. In contrast to the effects of well-understood chemical or biological
      agents, the exposure to magnetic-field intensities of 0.08, 0.1, 1.0 or 1.3 mT
      had no effect on the NF-kappaB or AP-1 signaling pathways.

PMID- 10073670
TI  - An EPR study of the transfer and trapping of holes produced by radiation in
      guanine(thioguanine) hydrochloride single crystals.
AB  - Single crystals of guanine hydrochloride monohydrate, guanine hydrochloride
      dihydrate and anhydrous guanine dihydrochloride, doped with thioguanine, were
      irradiated with X and gamma rays. In all three systems the dominant radicals were
      associated with thioguanine. In the former two systems the stabilized species is
      the thiyl radical, formed by initial loss of an electron at some of the guanines
      in the crystal lattice, followed by hole migration to thioguanine and subsequent
      deprotonation of the radical formed. In the anhydrous guanine(thioguanine)
      dihydrochloride, that process is followed by acquisition of a chlorine ion. In
      the guanine hydrochloride monohydrate and guanine hydrochloride dihydrate
      lattices, systems of interacting closely spaced stacked bases and strings of
      chloride ions might support the migration of electrons and/or holes. In anhydrous
      guanine dihydrochloride, neither the bases nor the Cl- ions alone are capable of
      providing the means for the long-range electron, energy and spin transfer. It is
      the interchangeable sequence of the charged bases and the Cl- ions that makes the
      supporting strings or networks. The ultimate chlorination of the thioguanine
      centered electron-loss radicals depends mainly on the availability of the Cl-
      ions and the space for their accommodation in the vicinity of the sulfur atom.

PMID- 10073671
TI  - Low-energy (5-25 eV) electron damage to homo-oligonucleotides.
AB  - Radiation-induced damage to homo-oligonucleotides is investigated by electron
      stimulated desorption of neutral fragments from chemisorbed organic films. Six
      and 12 mers of cytidine phosphate (poly dCs) and thymidine phosphate (poly dTs)
      are chemisorbed from various solutions onto a crystalline gold substrate by a
      thiol modification at the 3' end and are irradiated under ultra-high vacuum
      conditions with 5-25 eV electrons. The mass selected neutral desorption yields
      consist mainly of fragments of the DNA bases, i.e. CN and OCN (and/or H2NCN for
      poly dCs) from both poly dCs and poly dTs, indicating that the electrons interact
      specifically via fragmentation of the aromatic ring of either of the bases. Other
      heavier fragments are also detected such as H3CC-CO from poly dTs. The yields
      generally possess a threshold near 5 eV and a broad maximum around 12-13 eV
      incident electron energy. Dissociative electron attachment as well as
      electronically excited neutral or cation states are believed to be responsible
      for the various desorption yields. The latter yields are consistently larger for
      oligos chemisorbed from water and acetone solutions, compared to methanol
      solution. The invariance of the fragment yield intensities with oligo length
      suggests that the molecules are likely to adsorb almost parallel to the surface.

PMID- 10073672
TI  - Yield of DNA strand breaks after base oxidation of plasmid DNA.
AB  - We have irradiated aerobic aqueous solutions of plasmid DNA with 137Cs gamma rays
      in the presence of inorganic radical scavengers including nitrite, iodide, azide,
      thiocyanate and bromide. These scavengers react with the strongly oxidizing
      hydroxyl radical (*OH) to produce less powerful oxidants. Of these scavengers,
      only thiocyanate and bromide result in the formation of oxidizing species
      [(SCN)2*- and Br2*-, respectively] which are capable of reacting with the bases
      in DNA. The oxidized bases were detected after incubation of the irradiated
      plasmid with the two E. coli DNA base excision repair endonucleases,
      formamidopyrimidine-DNA N-glycosylase and endonuclease III. Depending on the
      experimental conditions, the intermediate base radicals may ultimately form
      stable oxidized bases in very high yields (within an order of magnitude of the
      *OH yield), and possibly also single-strand breaks (SSBs) in much lower yield
      (between 0.1 and 1% of the total yield of base damage). By competing for (SCN)2*-
      with an additional species (nitrite), it was possible to estimate the second
      order rate constant for the reaction of (SCN)2*- with DNA as 1.6 x 10(4) dm3 mol(
      1) s(-1), and also to demonstrate a correlation between the large yield of
      damaged bases and the much smaller increase in the yield of SSBs over background
      levels due to *OH. The efficiency of transfer of damage from oxidized base to
      sugar is estimated as about 0.5% or 5%, depending on whether purine or pyrimidine
      base radicals are responsible for the base to sugar damage transfer.

PMID- 10073673
TI  - Antioxidant effect of probucol on RO2*/O2(*-)-induced peroxidation of human low
      density lipoproteins.
AB  - This study was designed to evaluate the antioxidant effect of probucol on
      peroxidation of low-density lipoproteins (LDLs) initiated by oxygenated free
      radicals (O2*-) and ethanol-derived peroxyl radicals (RO2*) generated by gamma
      radiolysis. Initial radiolytic yields related to the markers of lipid
      peroxidation [i.e. decrease in endogenous alpha-tocopherol, formation of
      thiobarbituric acid-reactive substances (TBARS) and conjugated dienes] were
      determined as a function of LDL concentration (1.5 and 3 g l(-1), expressed as
      total LDL) and in the absence or the presence of probucol at different
      concentrations (2.3 x 10(-6), 3.5 x 10(-6), 9 x 10(-6) and 20.5 x 10(-6) mol l(
      1)). Our results showed that probucol was able to decrease not only the yields of
      TBARS and conjugated dienes but also the levels of these peroxidation products
      obtained at high doses (2500 Gy) compared to LDLs without probucol. Under our
      conditions, probucol displayed an optimal antioxidant effect for an initial
      concentration in LDLs equivalent to 15 probucol molecules per LDL particle, which
      corresponded to a pharmacologically relevant concentration of probucol. Moreover,
      our data showed that probucol was unable to react with RO2* and thus did not
      protect LDL vitamin E from free radical attack. In addition, the scavenging
      capacity of probucol on O2*- appeared to be very poor, and probucol more likely
      reacted with LDL intermediate radical products. Finally, a very significant
      steady-state level of probucol remained in LDLs at high doses (up to 2500 Gy),
      equivalent to at least 40% of the initial concentration of probucol. This
      addressed the question of a mechanism for regeneration of probucol in LDLs. Our
      results as a whole suggested that the antioxidant effect of probucol in vivo
      could not be explained by its scavenging capacity with regard to RO2*/O2*- free
      radicals.

PMID- 10073674
TI  - Radioprotection of human cell nuclear DNA by polyamines: radiosensitivity of
      chromatin is influenced by tightly bound spermine.
AB  - The polyamines putrescine (PUT) and spermine (SPM) were examined for their
      ability to protect human cell DNA against the formation of radiation-induced
      double-strand breaks (DSBs). As observed previously, under conditions where
      polyamines were shown to be almost completely absent, association with nuclear
      matrix protein into a nucleoid, and organization into chromatin structure,
      protected DNA from induction of DSBs by factors of 4.5 and 95, respectively. At
      concentrations below 1 mM, PUT or SPM provided equivalent levels of protection to
      deproteinized nuclear DNA, consistent with their capacity to scavenge radiation
      induced radicals. At constant ionic strength, 5 mM SPM protected deproteinized
      DNA and nucleoid DNA and DNA in nuclear chromatin by factors of 100 and 26,
      respectively. At 5 mM, SPM provided 15 times greater protection of deproteinized
      DNA than did PUT. Under physiologically relevant conditions, 5 mM SPM protected
      DNA in the intact nucleus from the induction of DSBs by a factor of 2 relative to
      DNA in the absence of SPM. Studies of SPM binding during cellular fractionation
      revealed that a significant fraction of the cellular SPM is tightly bound in the
      nucleus but can be removed by extended washing. Thus the association of SPM with
      nuclear chromatin appears to be a significant contributor to the resistance of
      the cell's DNA to the induction of DSBs.

PMID- 10073675
TI  - Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in
      irradiated mice.
AB  - The purpose of this study was to investigate effects of the treatment prior to
      irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis
      in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G
      CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h
      after the last injection of G-CSF. Such a treatment was found to stimulate
      granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor
      cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the
      time of irradiation. However, postirradiation counts of GM-CFC and granulocytic
      cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after
      irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after
      in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated
      with G-CSF, indicating a decreased radiosensitivity of these cells after drug
      treatment. The inhibitory effects of the pretreatment with G-CSF on the
      postirradiation granulopoiesis could be attributed to the phenomenon of "rebound
      quiescence" which can occur after cessation of the treatment with growth factors.
      Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with
      G-CSF exhibited a dramatic increase and compensated for the decreased
      erythropoiesis in the marrow at the time of irradiation. This complexity of the
      hematopoietic response should be taken into account when administering G-CSF in
      preirradiation regimens.

PMID- 10073676
TI  - Low-dose-rate radiation attenuates the response of the tumor suppressor TP53.
AB  - Acute low-dose irradiation (0.1-1 Gy, 1.33 Gy/min) of cells of a human
      glioblastoma cell line, A-172, induced a dose-dependent monophasic accumulation
      of TP53 (formerly known as p53) and CDKN1A (formerly known as WAF1). In contrast,
      chronic gamma irradiation (0.001 Gy/min) produced a clear biphasic response of
      accumulation TP53 with the first peak at 1.5 h (0.09 Gy) and the second peak at
      10 h (0.54 Gy). Significantly, when the cells were preirradiated with a chronic
      dose of gamma irradiation for 24 h (1.44 Gy) or 50 h (3 Gy), they no longer
      responded to an acute challenging dose to produce a dose-dependent response of
      the TP53 pathway. These findings suggest that chronic irradiation at low dose
      rate alters the TP53-dependent signal transduction pathway. Wearing away of the
      TP53 pathway by chronic exposure to radiation may have important implications for
      radiation protection.

PMID- 10073677
TI  - Inhibition of lung metastasis by adoptive immunotherapy using Iscador.
AB  - Adoptive immunotherapy using spleen cells activated with Iscador was found to
      inhibit tumour growth significantly (P<0.001). Metastatic B16F10 tumour bearing
      animals treated with a single dose of spleen cells activated with Iscador (in
      vitro) showed 100% inhibition of tumour nodule formation on 21st day. Single
      injection of splenocytes isolated from mice treated with Iscador inhibited the
      tumour nodule formation by 93.8%. Animals treated with in vivo and in vitro
      activated spleen cells along with Iscador had an increase in life span of 119%
      and 81% respectively. Treatment of animals with low dose of Iscador after
      adoptive immunotherapy further augmented the life span. Animals which underwent
      adoptive immunotherapy showed significantly reduced lung collagen hydroxyproline
      (9.8 microg/mg protein) and serum sialic acid (24.61 micro/ml serum) levels
      compared to control tumour bearing animals with increased levels of lung
      hydroxyproline (26.95 microg/mg protein) and serum sialic acid levels (151.3
      microg/ml serum). Serum gamma -glutamyl transpeptidase levels were found to be
      significantly reduced in the group of animals treated with Iscador and Iscador
      activated splenocytes (16.6+/-2.3 nmol P-nitroaniline released /ml serum) Group
      of animals treated with Iscador activated splenocytes alone also showed
      significantly reduced serum gamma - glutamyl transpeptidase levels (17.3+/-10
      nmol P-nitroaniline released /ml serum) compared to control tumour bearing
      animals (91+/-12 nmol P-nitroaniline released /ml serum).

PMID- 10073678
TI  - Relevance of sialoglycoconjugates in murine thymocytes during maturation and
      selection in the thymus.
AB  - Differentiation of most T lymphocytes is characterized not only by the variable
      expression of CD4/CD8 coreceptor molecules and increased surface density of the T
      cell antigen receptor, but also by changes in the glycosylation pattern of cell
      surface glycolipids or glycoproteins. In this work we evaluated the changes in
      the sialylation pattern in thymus sections from normal and dexamethasone treated
      mice. We used sialic acid specific lectins, such as Sambucus nigra agglutinin
      (SNA, NeuAcalpha2,6-Gal specific) and Maackia amurensis agglutinin (MAA,
      NeuAcalpha2,3-Gal specific). Our results indicate that the sialylation pattern
      was modified during the maturation process of thymic cells. The immature CD4-CD8-
      and CD4+CD8+ cortical thymocytes were recognized by SNA, whereas the mature
      single positive (CD4+ or CD8+) medullary cells, preferentially bound MAA lectin.
      However, in the corticomedullary region we found not only SNA+ cells, but also
      MAA+ cells. In the thymus of dexamethasone treated mice, the clusters of
      thymocytes undergoing apoptosis in the cortex were characteristically stained by
      SNA. These results suggest that in the initial stages of the differentiation
      pathway, a great number of thymocytes express an alpha2,6 linked sialic acid on
      their surface and as they progress to more mature stages there is a change in the
      sialylation pattern to alpha2,3 linked sialic acids probably due to a regulated
      expression of different sialyltransferases, which could be modulated by the
      thymic microenvironment.

PMID- 10073679
TI  - Development of chicken antibodies to bovine interferon alpha.
AB  - We have developed chicken polyclonal antibody to bovine interferon alpha
      (IFNalpha). Five hundred microg of recombinant bovine IFNalpha suspended with
      complete Freund's adjuvant was used in the first immunization round. A suspension
      of the same amount of IFNalpha and incomplete Freund's adjuvant was used for all
      subsequent boosters. The antibody was purified from egg yolks using polyethylene
      glycol precipitation. The first reactive antibody appeared several weeks after
      the first immunization. The antibody is specific for IFNalpha in immunoblotting,
      it is also useful in ELISA and immunohistochemistry. This method provides a fast,
      cheap and efficient alternative to development of monoclonal antibodies to
      conserved mammalian antigens.

PMID- 10073680
TI  - Phenotyping of immune cell infiltrates in breast and colorectal tumours.
AB  - White cell infiltration of solid tumors is an important prognostic indicator in
      malignant disease. Although macrophage infiltration is associated with good
      outcome in colorectal cancer, a high macrophage content is associated with poor
      prognosis in breast cancer. Suppressor macrophages prevent T cell activation in
      normal tissues such as mucosal linings exposed to continuous antigenic challenge.
      Interleukin 10 (IL-10), an immunosuppressive cytokine, inhibits macrophage co
      stimulation of T cells. Suppressor macrophage numbers, T cell numbers and T cell
      activation status were assessed in cell suspensions obtained from fresh specimens
      of breast and colorectal tumours and matched normal tissues. IL-10 production by
      both malignant and matched normal tissue was also assessed. This study identified
      elevated numbers of suppressor macrophages in breast tumors compared to matched
      normal breast tissue. Colorectal tumors did not contain significant numbers of
      these cells. Although T cell numbers are increased in breast tumors, these cells
      do not appear to be fully activated, as assessed by major histocompatibility
      complex class II and Interleukin 2 receptor expression. In contrast, T cells in
      colorectal tumors exhibit greater expression levels of these markers. Breast
      tumors produce significantly higher levels of IL-10 than normal breast tissue
      whereas IL-10 levels in colorectal tumors are similar to normal colon tissue. Our
      findings of high suppressor macrophage numbers, high levels of IL-10 and poorly
      activated T cells in breast tumors compared to low suppressor macrophage numbers,
      low IL-10 and fully activated T cells in colorectal tumors may explain why high
      macrophage content is associated with poor prognosis in breast cancer and good
      prognosis in colorectal malignancy.

PMID- 10073681
TI  - Coincidence of hereditary angioedema (HAE) with Crohn's disease.
AB  - A patient with two diseases, based presumably on different immunopathological
      mechanisms, hereditary angioedema (HAE) and Crohn's disease, was followed for 8
      years. For more than three years of this observation period, detailed laboratory
      data were also available and could be analyzed. Both diseases had severe courses
      requiring chronic treatment with danazol and sulfasalazine, respectively. During
      exacerbation of Crohn's disease, the levels of C4 was found to be significantly
      lower than during the periods free of symptoms of both diseases. This drop was
      probably due to an impaired C1-inhibitor activity. HAE attacks and acute
      exacerbation of Crohn's disease never occurred simultaneously. This finding may
      be a mere chance but may also indicate that the different immunopathological
      processes underlying HAE and Crohn's disease influence each other.

PMID- 10073682
TI  - Exposure of human peripheral blood mononuclear cells (PBMC) to hydrostatic
      pressure increases their proliferative response to phytohemagglutinin A (PHA) and
      anti-CD3 antibody.
AB  - In the present study we show that a brief exposure of human PBMC to hydrostatic
      pressure (HyP) increased their proliferative response to PHA and anti-CD3
      antibody, assessed by DNA synthesis. The effect of HyP was most prominent at 400
      atmospheres of HyP followed by 600 and 200 atmospheres. At any pressure level,
      the highest effect of HyP was noted when employing PHA and anti-CD3 antibody at
      10(-2) dilution. When PBMC were exposed to 400 atmospheres HyP, maximal effect
      was achieved at 20 minutes of exposure. The highest effect of HyP on DNA
      synthesis was noted at 48 and 72 hours of incubation with PHA, when exposing
      cells to pressure for 20 minutes at 400 atmospheres. Exposure of PBMC under
      similar conditions for 40 minutes, caused an increase in DNA synthesis only at 48
      hours incubation with PHA. These results demonstrate that exposure of human PBMC
      to HyP increases their proliferative response to different polyclonal activators.
      The possible mechanisms involved in this phenomenon are discussed.

PMID- 10073683
TI  - Preferential enhancement of B cell IgA secretion by intestinal epithelial cell
      derived cytokines and interleukin-2.
AB  - Intestinal epithelial cells (IEC) are known to secrete a number of important
      cytokines. Recently, we determined that IEC-derived IL-6 and TGF-beta could
      enhance IgA secretion and suppress IgM secretion by isolated mucosal B cells.
      However, since the IEC-derived cytokines must function in the context of locally
      produced T cell cytokines, the effect of IEC- and T cell-derived cytokines on
      mucosal B cell immunoglobulin secretion was determined. Using 4 day culture
      supernatants (IEC-SN) from the rat IEC-6 intestinal epithelial cell line and
      lipopolysaccharide (LPS) stimulated Peyer's patch or mesenteric lymph node B
      cells, the IEC- SN was found to act with IL-2 to greatly enhance IgA secretion
      but limit or suppress IgM secretion as compared to cultures of LPS stimulated B
      cells alone. However, neither IL-4, IL- 5, nor IFN-gamma affected IgA secretion
      with the IEC-SN. Depletion of the IEC-SN with specific anti-cytokine antibodies
      suggested that IEC-derived TGF-beta and IL-6 were both responsible for the
      enhancing effect along with IL-2 on IgA secretion, whereas IEC-derived TGF-beta
      alone limited or suppressed IgM secretion. These results suggest that cytokines
      derived from local IEC and T cells may create an environment which may contribute
      to the preferential enhancement of IgA secretion seen in mucosal tissues.

PMID- 10073684
TI  - Cell surface markers and circulating cytokines in graft versus host disease.
AB  - Graft versus host disease (GVHD) remains the major obstacle to the widespread
      application of allogeneic bone marrow transplantation (BMT) despite improvement
      in drug prophylaxis. T cells in the donor bone marrow recognize and react against
      host alloantigens and thereby initiate GVHD, but the precise mechanisms by which
      host tissues are damaged remain unclear. In the current study, we determined the
      cytokine secretion, cell population distribution, and cell surface markers
      expression by ELISA and flow cytometer, to understand further the pathophysiology
      of GVHD. Our results demonstrated that there was no significant change in the
      cell ratio of B-and T- lymphocytes, and helper/suppressor cells during GVHD
      development when compared to the condition before transplantation. Furthermore,
      the percentage of natural killer cells, the interleukin-2 receptor (IL-2R) or the
      HLA-DR antigen on both CD4 and CD8 positive cells presented no significant
      difference between pre-transplantation and during GVHD. The serum cytokine
      secretion of IL-1, TNF-alpha, IL-2, ICAM-1, endothelin, TGF-beta showed no
      difference before BMT and during GVHD. However, when patients in the developing
      of GVHD, there was significant difference in the serum levels of soluble IL-2R
      (slL-2R), epidermal growth factor (EGF), and platelet derived growth factor
      (PDGF). In addition, with patients who develop GVHD, the mixed lymphocyte
      reaction also presented a significant difference. This study indicated that some
      serum cytokines such as sIL-2R, growth factors, and the mixed lymphocyte reaction
      may be used as parameters for the early detection of the development of GVHD.

PMID- 10073685
TI  - Identification of neutralizing epitopes on a European strain of swine vesicular
      disease virus.
AB  - Six neutralizing monoclonal antibodies (MAbs) were used to isolate MAb
      neutralization-resistant (MAR) mutants from a recent European strain of swine
      vesicular disease virus (SVDV), ITL/9/93. Sequencing of MAR mutants identified
      two epitopes located at positions analogous to sites 2A (VP2) and 3B (VP3) on
      poliovirus (PV) which have been previously identified on a Japanese strain of
      SVDV. A third epitope near to the C terminus of VP1, not previously recognized on
      SVDV, was tentatively identified in a region analogous to site 1 of PV. A fourth
      epitope, located in the C-terminal region of VP3, has never before been
      recognized as a site of neutralization on picornaviruses. All four epitopes were
      predicted to be surface-exposed.

PMID- 10073686
TI  - Serum albumin inhibits echovirus 7 uncoating.
AB  - Echoviruses induce a wide spectrum of diseases in man, the most severe being
      meningitis. In neonates, however, a severe systemic infection can be observed,
      leading to death. Serum albumin is the most abundant protein in plasma and most
      interstitial fluids, and its functions include osmoregulation and transport and
      delivery of hydrophobic molecules such as fatty acids and steroids. The results
      of cold-synchronized one-step growth analysis of echovirus 7 infection and
      sucrose-gradient analysis of A-particles suggest that physiological
      concentrations of albumin block echovirus 7 infection by inhibiting uncoating.
      The blockage was reversible and was still effective when albumin was added 30 min
      after virus adsorption. Inhibition of uncoating was confirmed by using rhodanine,
      a known specific inhibitor of echovirus uncoating. After removal of the albumin
      blockage, addition of rhodanine perpetuated the inhibition. Serum and
      interstitial albumin concentrations may limit echovirus infection in vivo and
      thereby act as an extracellular determinant for echovirus tropism.

PMID- 10073687
TI  - Identification of further proteolytic cleavage sites in the Southampton
      calicivirus polyprotein by expression of the viral protease in E. coli.
AB  - Southampton virus (SV) is a human enteric calicivirus with a positive-sense RNA
      genome which encodes a protease as part of a large precursor polyprotein.
      Expression vectors based on pRSET were constructed carrying the entire 3C-like
      viral protease (3Cpro) sequence together with flanking sequences from a region of
      the viral genome 3'-distal to the putative helicase-encoding region. Expression
      from these vectors in E. coli resulted in discrete protein products with smaller
      than expected molecular sizes. This confirmed that an active viral protease was
      produced in E. coli and that the protease was capable of cleaving the expressed
      protein at defined sites. Expressed cleavage products surrounding the protease
      region of the viral polyprotein were separated by SDS-PAGE, transferred to PVDF
      membranes and subjected to N-terminal sequence analysis. Cleavage occurred at an
      EG dipeptide at the N terminus of the putative VPg (961E/GKNKG) and also at the
      protease/polymerase boundary (1280E/GGDKG). The N terminus of the protease was
      released from the VPg C terminus at an EA dipeptide in the sequence 1099E/APPTL.
      These studies demonstrate that SV enteric calicivirus encodes a 3C-like protease
      with a specificity similar to the picornaviral 3C protease and that the SV
      polyprotein is cleaved into at least six mature products.

PMID- 10073688
TI  - Entry of porcine reproductive and respiratory syndrome virus into porcine
      alveolar macrophages via receptor-mediated endocytosis.
AB  - Porcine alveolar macrophages (AMphi) are the dominant cell type that supports the
      replication of porcine reproductive and respiratory syndrome virus (PRRSV) in
      vivo and in vitro. In order to determine the characteristics of the virus
      receptor interaction, the attachment of PRRSV to cells was examined by using
      biotinylated virus in a series of flow cytometric assays. PRRSV bound
      specifically to AMphi in a dose-dependent manner. Binding of PRRSV to AMphi
      increased gradually and reached a maximum within 60 min at 4 degrees C. By
      confocal microscopy, it was shown that different degrees of PRRSV binding exist
      and that entry is by endocytosis. Virus uptake in vesicles is a clathrin
      dependent process, as it was blocked by the addition of cytochalasin D and co
      localization of PRRSV and clathrin was found. Furthermore, by the use of two weak
      bases, NH4Cl and chloroquine, it was demonstrated that PRRSV uses a low pH
      dependent entry pathway. In the presence of these reagents, input virions
      accumulated in large vacuoles, indicating that uncoating was prevented. These
      results indicate that PRRSV entry into AMphi involves attachment to a specific
      virus receptor(s) followed by a process of endocytosis, by which virions are
      taken into the cell within vesicles by a clathrin-dependent pathway. A subsequent
      drop in pH is required for proper virus replication.

PMID- 10073689
TI  - North American and European porcine reproductive and respiratory syndrome viruses
      differ in non-structural protein coding regions.
AB  - Although North American and European serotypes of porcine reproductive and
      respiratory syndrome virus (PRRSV) are recognized, only the genome of the
      European Lelystad strain (LV) has been sequenced completely. Here, the genome of
      the pathogenic North American PRRSV isolate 16244B has been sequenced and
      compared with LV. The genomic organization of 16244B was the same as LV but with
      only 63.4% nucleotide identity. The 189 nucleotide 5' non-coding region (NCR) of
      16244B was distinct from the LV NCR, with good conservation (83%) only over a 43
      base region immediately upstream of open reading frame (ORF) 1a. Major
      differences were found in the region encoding the non-structural part of the
      ORF1a polyprotein, which shared only 47% amino acid identity over 2503 residues
      of the six non-structural proteins (Nsps) encoded. Nsp2, thought to have a
      species-specific function, showed the greatest divergence, sharing only 32% amino
      acid identity with LV and containing 120 additional amino acids in the central
      region. Nsps encoded by the 5'-proximal and central regions of ORF1b had from 66
      to 75% amino acid identity; however, the carboxy-terminal protein CP4 was
      distinct (42% identity). The ORF 1a-1b frameshift region of 16244B had 98%
      nucleotide identity with LV. Consistent with previous reports for North American
      isolates, the six structural proteins encoded were 58 to 79% identical to LV
      proteins. The 3' NCR (150 nucleotides) was 76% identical between isolates. These
      genomic differences confirm the presence of distinct North American and European
      PRRSV genotypes.

PMID- 10073690
TI  - Ontogeny of hepatitis C virus (HCV) hypervariable region 1 (HVR1) heterogeneity
      and HVR1 antibody responses over a 3 year period in a patient infected with HCV
      type 2b.
AB  - Hypervariable region 1 (HVR1) sequences of 96 clones at six time-points
      representing 27 variants in two major and one minor group were identified in a
      patient with chronic hepatitis C virus (HCV) infection over 3 years. Major and
      selected minor variants were used to design synthetic peptides corresponding to
      the HVR1 C terminus. Peptide ELISA reactivity with IgG was plotted against the
      corresponding clone frequency, and three patterns emerged: (1) three peptides
      were unreactive; (2) antibodies against two peptides followed emergence of the
      corresponding variant, suggesting isolate-specificity; (3) antibodies against
      four peptides preceded the appearance of the corresponding variant, indicating
      cross-reactivity or previous exposure. Cross-reactivity was investigated further:
      sera from six time-points were tested against 11 unrelated HVR1 peptides, seven
      of which (63.6%) showed cross-reactivity at all time-points. Cross-reactivity of
      nine patient-specific peptides tested against a panel of 45 heterologous sera
      from chronic HCV carriers ranged between 0 and 20%. Only three of 27 variants
      appeared at more than one time-point and in two cases specific and/or cross
      reactive HVR1 antibodies coexisted with the corresponding variant, consistent
      with emergence of escape mutants. In addition, analysis of HVR1 IgG reactivity
      within a group of closely related patient-specific peptides revealed a loss of
      reactivity in one peptide attributable to a single amino acid substitution.
      Interferon-alpha treatment considerably reduced viral RNA but, paradoxically,
      heterogeneity increased.

PMID- 10073691
TI  - Mutations in the retinoblastoma protein-binding LXCXE motif of rubella virus
      putative replicase affect virus replication.
AB  - The rubella virus (RV)-encoded protein NSP90, which contains the retinoblastoma
      protein (Rb)-binding motif LXCXE, interacts with Rb and RV replication is reduced
      in cells lacking Rb. Whether the LXCXE motif of RV NSP90 itself is essential for
      Rb binding and virus replication is not known. Therefore, in the present study,
      the functional role of this motif was investigated by site-directed mutagenesis
      in a plasmid from which infectious RV RNA can be produced. Three critical
      mutations in the motif, two substitutions at the conserved cysteine residue (C -
      > G and C --> R) and a deletion of the entire motif, were created. A cell-free
      translated NSP90 C terminus polypeptide containing the deletion did not bind to
      Rb and a polypeptide carrying the C --> R substitution had barely detectable
      binding affinity for Rb. Rb binding by the C --> G mutant was reduced
      significantly compared to that of wild-type protein. Correlating with the binding
      results, mutant viruses containing the LXRXE and LXGXE motifs had a reduction in
      replication to < 0.5% and 47% of the wild-type, respectively, while deletion of
      the motif was found to be lethal. By the first serial passage, replication of the
      LXRXE-carrying virus had increased from < 0.5% to 2% of the wild-type. Sequencing
      of the genome of this virus revealed a nucleotide change that altered the motif
      from LXRXE to LXSXE, which is a known Rb-binding motif in two protein phosphatase
      subunits. Thus, our results clearly demonstrate that the LXCXE motif is required
      for efficient RV replication.

PMID- 10073692
TI  - Two non-structural rotavirus proteins, NSP2 and NSP5, form viroplasm-like
      structures in vivo.
AB  - In rotavirus-infected cells, the non-structural proteins NSP5 and NSP2 localize
      in complexes called viroplasms, where replication and assembly occur. Recently,
      we have demonstrated direct interaction of NSP5 with NSP2, and as a consequence
      of that, up-regulation of NSP5 hyperphosphorylation. To investigate a possible
      structural role for the NSP2-NSP5 interaction, we analysed the cytoplasmic
      distribution of the two proteins in transfected cells by immunofluorescence using
      specific antibodies. Here we report that NSP2 and NSP5 can drive the formation of
      viroplasm-like structures (VLS) in the absence of other rotaviral proteins and
      rotavirus replication. Several NSP5 deletion mutants were constructed and
      expressed in combination with NSP2. Both the N- and C-terminal domains of NSP5
      were found to be essential for VLS formation. Only one mutant, with an internal
      deletion of residues 81-130, was able to interact with NSP2 to form VLS. Analysis
      of the phosphorylation capacity of the different mutants in vivo indicated that
      hyperphosphorylation of NSP5 is necessary, but not sufficient, for VLS formation.
      Our results suggest a role for the non-structural protein NSP5 in the structure
      of viroplasms mediated by its interaction with NSP2.

PMID- 10073693
TI  - Genetic and antigenic variation of capsid protein VP7 of serotype G1 human
      rotavirus isolates.
AB  - The deduced amino acid sequences of the outer capsid protein, VP7, of serotype G1
      rotavirus clinical isolates collected over a 6 year period (1990-1995) in
      Melbourne, Australia, were examined. Phylogenetic analysis characterized the
      sequences into two discrete clusters representing two of the four global lineages
      of human G1 VP7 proteins. Antigenic characterization using a panel of serotype G1
      specific neutralizing monoclonal antibodies classified lineage II isolates (1990
      1993) as monotype G1a while lineage I isolates were classified as monotype G1b
      (1993-1995). Examination of the sequences of the neutralization epitope regions
      of VP7 revealed a particular amino acid substitution at residue 94 in region A
      (Asp --> Ser/Thr) that correlated with lineage and monotype designation. Our
      results indicated that temporal genetic variation of the VP7 of serotype G1
      rotaviruses was associated with changes in the antigenicity of these isolates.

PMID- 10073694
TI  - Development and use of a 293 cell line expressing lac repressor for the rescue of
      recombinant adenoviruses expressing high levels of rabies virus glycoprotein.
AB  - An expression cassette designed for high-level production of rabies virus
      glycoprotein (RG) could not be rescued into a replication-defective, adenovirus
      based vector using standard procedures. To overcome this difficulty, a 293-based
      cell line, designated 293LAP13, was constructed that contained and expressed a
      derivative of the lac repressor protein. The lac operator sequence, to which the
      repressor binds, was incorporated into an expression cassette, containing a
      promoter and intron, designed for high-level production of RG. Insertion of a
      single operator sequence immediately downstream of the transcription start site
      and the use of the 293LAP13 cell line allowed recombinant viruses that could not
      be isolated with 293 cells to be rescued efficiently. The operator-containing
      virus reached higher titres in 293LAP13 than in parental 293 cells and also
      produced plaques more efficiently in 293LAP13 cells. Moreover, in non
      complementing human and canine cell lines, adenovirus vectors with a promoter
      intron expression cassette expressed RG at much higher levels than vectors
      lacking the intron. These observations, together with the demonstration that
      expression of RG by operator-containing vectors was repressed markedly in
      293LAP13 cells and that this inhibition was relieved at least partly by IPTG,
      suggest that the 293LAP13 cell line may be useful for the rescue and propagation
      of many vectors in which high expression of the desired protein prevents vector
      rescue in 293 cells.

PMID- 10073695
TI  - Characterization of the L gene and 5' trailer region of Ebola virus.
AB  - The nucleotide sequences of the L gene and 5' trailer region of Ebola virus
      strain Mayinga (subtype Zaire) have been determined, thus completing the sequence
      of the Ebola virus genome. The putative transcription start signal of the L gene
      was identical to the determined 5' terminus of the L mRNA (5' GAGGAAGAUUAA) and
      showed a high degree of similarity to the corresponding regions of other Ebola
      virus genes. The 3' end of the L mRNA terminated with 5' AUUAUAAAAAA, a sequence
      which is distinct from the proposed transcription termination signals of other
      genes. The 5' trailer sequence of the Ebola virus genomic RNA consisted of 676 nt
      and revealed a self-complementary sequence at the extreme end which may play an
      important role in virus replication. The L gene contained a single ORF encoding a
      polypeptide of 2212 aa. The deduced amino acid sequence showed identities of
      about 73 and 44% to the L proteins of Ebola virus strain Maleo (subtype Sudan)
      and Marburg virus, respectively. Sequence comparison studies of the Ebola virus L
      proteins with several corresponding proteins of other non-segmented, negative
      strand RNA viruses, including Marburg viruses, confirmed a close relationship
      between filoviruses and members of the Paramyxovirinae. The presence of several
      conserved linear domains commonly found within L proteins of other members of the
      order Mononegavirales identified this protein as the RNA-dependent RNA polymerase
      of Ebola virus.

PMID- 10073696
TI  - The cytoplasmic tail of the influenza C virus glycoprotein HEF negatively affects
      transport to the cell surface.
AB  - The surface glycoprotein, HEF, of influenza C virus (C/Johannesburg/1/66) has
      been shown to undergo a post-translation conformational change that is evident in
      a dramatic change of electrophoretic mobility. If the corresponding gene is
      expressed in the absence of other viral proteins, this folding process does not
      occur at all or only very inefficiently. A chimaeric protein, HEF-HA(Tail), in
      which the short cytoplasmic tail (Arg-Thr-Lys) of HEF was replaced by the
      cytoplasmic tail of the haemagglutinin of an influenza A virus (fowl plague
      virus) was constructed. In contrast to the wild-type protein, the chimaeric
      protein was detected on the cell surface. No further improvement of the surface
      expression was observed when both the transmembrane domain and the cytoplasmic
      tail were replaced by the corresponding domains of either the influenza A
      haemagglutinin or gp40, an endogenous protein of MDCK cells. For the HEF-HA(Tail)
      construct this study shows that a substantial amount of the protein is converted
      to the 100 kDa mature form that is observed in virus-infected cells. The HEF-HA
      expressed on the cell surface reacted positively in esterase and haemadsorption
      assays, indicating that it was present in a biologically active form. The results
      show that the short cytoplasmic tail of HEF has a negative effect on the folding
      and surface transport of this protein. How this effect may be prevented during a
      virus infection is discussed.

PMID- 10073697
TI  - Isolation and characterization of Dobrava hantavirus carried by the striped field
      mouse (Apodemus agrarius) in Estonia.
AB  - Dobrava hantavirus (DOB) was isolated from the striped field mouse (Apodemus
      agrarius) trapped on Saaremaa Island, Estonia, and its genetic and antigenic
      characteristics were subsequently analysed. Phylogenetic analysis showed that the
      Estonian DOB strain, together with several wild strains carried by Apodemus
      agrarius, forms a well-supported lineage within the DOB clade. The topography of
      the trees calculated for the S, M and L nucleotide sequences of the Estonian DOB
      suggests a similar evolutionary history for all three genes of this virus and,
      therefore, the absence of heterologous reassortment in its evolution. A cross
      neutralization comparison of the Estonian virus with the prototype DOB, isolated
      from a yellow-necked mouse (A. flavicollis) in Slovenia, revealed 2- to 4-fold
      differences in the end-point titres of rabbit and human antisera. When studied
      with a panel of 25 monoclonal antibodies (MAbs), the Estonian and Slovenian DOB
      isolates showed similar antigenic patterns that could be distinguished by two
      MAbs. Genetic comparison showed sequence differences in all three genome segments
      of the two DOB isolates, including an additional N-glycosylation site in the
      deduced sequence of the G2 protein from the Estonian virus. Whether any of these
      mutations relates to the different rodent hosts rather than to the distant
      geographical origin of the two isolates remains to be resolved. Taken together,
      our observations suggest that A. agrarius, which is known to harbour Hantaan
      virus in Asia, carries another hantavirus, DOB, in north-east Europe.

PMID- 10073698
TI  - The adenoviral E1A oncoproteins interfere with the growth-inhibiting effect of
      the cdk-inhibitor p21(CIP1/WAF1).
AB  - The cdk-inhibitor p21(CIP1/WAF1) inhibits the activities of cyclin-dependent
      kinases and proliferating cell nuclear antigen, thereby repressing cell-cycle
      progression and DNA replication. Transforming oncogenes, such as E1A of human
      adenovirus 5 (Ad5), may interfere with such growth-inhibitory proteins. In this
      study, we show that in various Ad5E1-transformed cells, p21(CIP1/WAF1) is
      expressed and that, in general, expression is not downregulated. In addition,
      colony-formation assays show that in Ad5E1-transformed cells highly overexpressed
      p21(CIP1/WAF1) can still cause growth inhibition. FACS experiments indicate,
      however, that a G1 arrest induced by moderate overexpression of p21(CIP1/WAF1)
      can be overcome by E1A. The E1A proteins may interfere with the function of
      p21(CIP1/WAF1) by binding. Indeed, p21(CIP1/WAF1) binds with its cyclin/cdk
      binding N terminus to the transforming N-terminal and CR1 region of the E1A
      proteins. Together, these results lend support to the model that E1A can
      interfere directly with p21(CIP1/WAF1) function and thereby stimulates cell
      growth.

PMID- 10073699
TI  - Sexual behaviour and papillomavirus exposure in cervical intraepithelial
      neoplasia: a population-based case-control study.
AB  - Sexual history is an established risk determinant for cervical neoplasia. It is
      not clear if human papillomavirus (HPV) exposure entirely explains the sexual
      behaviour-related risk or if other sexually transmitted agents may act as
      cofactors for HPV in carcinogenesis. The aim of this study was to elucidate
      whether HPV exposure or HPV persistence explains the sexual history-related risk
      of high-grade cervical intraepithelial neoplasia (CIN) using a population-based
      case-control study of most of the 254 women referred to colposcopy in the
      Vasterbotten county in Sweden because of an abnormal cervical smear during
      October 1993 to December 1995 and 320 age-matched women from the general
      population. The women were interviewed for sexual history and tested for presence
      of serum antibodies to HPV-16, -18 and -33 as well as for presence of HPV DNA in
      cervical brush samples. HPV-16, -18 and -33 seropositivity was specific for the
      corresponding type of HPV DNA, dependent on the lifetime sexual history and
      associated with a two- to threefold increased risk of CIN 3. There was no sexual
      history-related risk of CIN among HPV-seropositive women and adjustment for HPV
      DNA presence explained the sexual history-related risk of CIN. In conclusion, HPV
      exposure appeared to explain the sexual history-related risk of high-grade CIN.

PMID- 10073700
TI  - Immune responses against human papillomavirus (HPV) type 16 virus-like particles
      in a cohort study of women with cervical intraepithelial neoplasia. I.
      Differential T-helper and IgG responses in relation to HPV infection and disease
      outcome.
AB  - T-helper (Th) cell-dependent IL-2 production and plasma IgG responses to virus
      like particles consisting of the human papillomavirus type 16 (HPV-16) major
      capsid protein L1 (L1-VLP) were determined in patients with cytological evidence
      of cervical intraepithelial neoplasia (CIN) participating in a non-intervention
      prospective cohort study. IgG responses were associated with HPV-16 persistence
      and high-grade CIN lesions, while high frequencies of Th responses were observed
      in patients with both virus clearance and virus persistence, irrespective of CIN
      grade. The IgG response was found in conjunction with an IL-2 response to L1-VLP
      in 87% of the patients. Recognition of the HPV-16 L1 Th epitope (amino acids 311
      335) was found to be more closely associated than recognition of L1-VLP as a
      whole to HPV exposure and CIN development. Among the HPV-16+ patients included in
      this study, those showing a Th response to amino acids 311-335 were more likely
      to carry the HLA DRB1*11/DQB1*0301 haplotype, while those showing an IgG response
      to L1-VLP were more likely to carry DRB1*0101/DQB1*0501. However, neither cell
      mediated nor humoral immune responses against HPV-16 L1 appear to be sufficient
      for the natural control of HPV infection and CIN development.

PMID- 10073701
TI  - Immune responses against human papillomavirus (HPV) type 16 virus-like particles
      in a cohort study of women with cervical intraepithelial neoplasia. II. Systemic
      but not local IgA responses correlate with clearance of HPV-16.
AB  - To investigate whether there is an association between local or systemic IgG and
      IgA responses against human papillomavirus (HPV) type 16 virus-like particles
      (VLP) containing L1 and L2 and the possible influence of these responses on
      clearance of HPV-16 and its associated lesions, cervical mucus samples from 125
      patients and plasma samples from 100 patients, all participating in a non
      intervention cohort study of women with abnormal cytology, were analysed. The
      results show that local IgG and IgA HPV-16 VLP-specific antibodies do not
      correlate with virus clearance. However, systemic IgG responses were more
      frequently detected in patients with a persistent infection (11/24) compared with
      patients with cleared HPV-16 infections (3/28, P = 0.006). Furthermore, the
      ultimate development of high-grade lesions was associated with systemic VLP
      specific IgG reactivity (P = 0.026). By contrast, systemic IgA responses were
      correlated with virus clearance (7/28 clearance compared with 1/24 persistence
      patients, P = 0.06). This correlation was statistically significant when only
      those clearance patients who tested HPV-16 DNA-positive at more than one visit
      were included in the analysis (5/11 compared with 1/24, P = 0.007). As these
      systemic IgA responses were not accompanied by local IgA responses, the systemic
      IgA responses in HPV-16 clearance patients are suggested to be a by-product of a
      successful cellular immune response induced at the local lymph nodes, mediated by
      cytokines.

PMID- 10073702
TI  - Determination and phylogenetic analysis of partial sequences from TT virus
      isolates.
AB  - Sera from French in-patients were tested for the presence of the TT virus (TTV)
      genome using PCR and degenerate primers located in ORF1. Thirty-six sequences
      were determined and compared with those deposited in databases, revealing a high
      degree of genetic variability between TTV isolates (up to 47% for amino acid
      sequences). Phylogenetic analysis demonstrated the existence of three main groups
      corresponding to the previously described genotypes 1 and 2 and to a new genotype
      3. Isolates could be assigned to distinct genotypes if their genetic distance was
      > 27%. No comparable genetic criteria were found for the definition of sub-types
      in the region studied. A 15-31 month follow-up of three haemodialysis patients
      proved the existence of chronic infection by TTV. In one patient, two strains
      belonging to different genotypes were detected at the same time. Sequences of
      both ORF1 and ORF2 remained unchanged for a given strain during the follow-up.

PMID- 10073703
TI  - Complementation of P37 (F13L gene) knock-out in vaccinia virus by a cell line
      expressing the gene constitutively.
AB  - Vaccinia virus produces two different infectious forms, intracellular mature
      virus (IMV) and extracellular enveloped virus (EEV). Acquisition of the EEV
      envelope occurs by wrapping of IMV with vesicles of the trans-Golgi network
      (TGN). The most abundant protein in the envelope of EEV, P37, is a 37 kDa
      palmitylated protein encoded by the F13L gene. P37 is located in the inner side
      of the EEV envelope and accumulates in the TGN during infection. Deletion of gene
      F13L results in a severe defect in the wrapping process, although normal levels
      of IMV are produced. A cell line, derived from RK-13 cells, was obtained that
      stably expressed P37 (RK(P37)), and the properties of the protein were studied in
      the absence of other viral polypeptides. P37 produced in RK(P37) cells differed
      from P37 produced in vaccinia-infected cells in terms of hydrophobicity and
      intracellular distribution. Despite these differences, RK(P37) cells partially
      complemented the phenotypic defect of vaccinia virus P37- mutants. EEV production
      and cell-to-cell virus spread by mutant viruses were increased significantly in
      RK(P37) cells when compared to normal RK-13 cell cultures. Infection of RK(P37)
      cells with P37- virus substantially altered the hydrophobicity and the
      intracellular distribution of P37 in those cells. These results indicate the
      requirement of the infection context for determination of the normal
      palmitylation and intracellular localization of P37.

PMID- 10073704
TI  - Macropodid herpesviruses 1 and 2 occupy unexpected molecular phylogenic positions
      within the Alphaherpesvirinae.
AB  - The molecular phylogeny of macropodid herpesviruses 1 and 2 (MaHV-1 and -2) has
      been investigated by cloning and sequencing the genes encoding glycoprotein B
      from both viruses. Phylogenetic reconstructions based on the putative amino acid
      sequences of glycoprotein B indicate that MaHV-1 and -2 are most closely related
      to the subfamily Alphaherpesvirinae. Within the Alphaherpesvirinae, MaHV-1 and -2
      are closely associated with those herpesviruses that infect primates. This
      phylogenetic relationship does not fit the constraints of the proposed co
      evolution theory described for other members of the Alphaherpesvirinae which have
      mammalian hosts.

PMID- 10073705
TI  - The R27080 glycoprotein is abundantly secreted from human cytomegalovirus
      infected fibroblasts.
AB  - A 45 kDa glycoprotein was purified from the culture media of human
      cytomegalovirus (HCMV)-infected fibroblasts. N-terminal sequencing revealed that
      the protein, R27080, is the translation product of the R27080 open reading frame
      of HCMV. R27080 is highly glycosylated and contains no cysteine or methionine
      residues. Proteolytic cleavage of R27080 by a furin-like enzyme was analysed in
      transfected COS-7 cells. R27080 is the first identified viral protein secreted
      from HCMV-infected cells.

PMID- 10073706
TI  - A-type and B-type Epstein-Barr virus differ in their ability to spontaneously
      enter the lytic cycle.
AB  - In this study replication of A-type and B-type Epstein-Barr virus (EBV) strains
      has been assessed. A-type and B-type type lymphoblastoid cell lines (LCLs) were
      established by infecting B lymphocytes, isolated from five EBV-seropositive
      donors, with different A-type and B-type virus isolates. The presence of viral
      capsid antigens (VCA) in these LCLs was determined by immunofluoresence assay and
      by immunoblotting. All of the B-type EBV strains were capable of spontaneously
      generating virus regardless of the origin of the donor cells. In contrast the A
      type strains, other than strain IARC-BL36, did not readily produce VCA in any of
      the different donor lymphocytes used. This study demonstrates another biological
      difference between the two virus types: their ability to spontaneously enter the
      lytic cycle.

PMID- 10073707
TI  - The major immunogenic epitopes of Epstein-Barr virus (EBV) nuclear antigen 1 are
      encoded by sequence domains which vary among nasopharyngeal carcinoma biopsies
      and EBV-associated cell lines.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a protein expressed
      consistently in EBV-infected cells and EBV-associated malignant tissues. A panel
      of monoclonal antibodies (MAbs) was generated against the C terminus of EBNA-1
      and evaluated for the detection of EBNA-1 in different cell lines. The epitopes
      recognized were mapped. Since sequence variations of EBNA-1 have been reported in
      nasopharyngeal carcinoma (NPC) tissues and in infected healthy individuals, the
      ability of these MAbs to recognize a recombinant protein derived from an NPC
      biopsy was also analysed. MAb 4H11 appeared to react with EBNA-1 sequences from
      different sources, whereas MAbs 5C11, 5F12 and 8F6 failed to recognize a
      recombinant EBNA-1 protein cloned from an NPC patient. Using different
      recombinant EBNA-1 fragments in an immunoblot format, this study demonstrates
      that the domain bounded by amino acids 408 and 498 is very immunogenic in mice in
      that epitopes in this region are recognized by various MAbs. Amino acid sequences
      of EBNA-1 were also deduced from nucleotide sequences amplified from three
      Burkitt's lymphoma cell lines, two spontaneous lymphoblastoid cell lines, two NPC
      biopsies and one NPC hybrid cell line, NPC-KT, and compared to the sequence from
      B95-8. The amino acid sequence of EBNA-1 in Akata is almost identical to that in
      an NPC biopsy, except for amino acid 585. The results of this study indicate that
      the immunogenic epitopes of EBNA-1 are highly variable.

PMID- 10073708
TI  - Relative levels of EBNA1 gene transcripts from the C/W, F and Q promoters in
      Epstein-Barr virus-transformed lymphoid cells in latent and lytic stages of
      infection.
AB  - Four promoters, Cp, Wp, Fp and Qp, are known to participate in transcription of
      the Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) gene in EBV-infected cell
      lines. The promoters are used differentially during the different phases of
      infection and establishment of the stages of latency. This has raised questions
      about the regulation of the promoters and the molecular mechanisms underlying the
      switches between them. To obtain a measure of the activity of the different EBNA1
      transcription units in EBV-transformed cell lines of different phenotypes, RNA
      probes were constructed that allowed the detection and relative quantification,
      by RNase protection analysis, of EBNA1 transcripts initiated at Fp and Qp and, in
      an indirect manner, Cp/Wp. RNase protection and PCR assays were performed with
      cytoplasmic RNA from B-lymphoid cell lines in latency stages I, II-III and III
      and after induction of the virus lytic cycle. The experiments demonstrated that,
      in addition to previously identified EBNA1 transcripts, cell lines of all latency
      types also contained different mRNAs that carried sequences from the EBNA1
      encoding K exon. Induction of the virus lytic cycle resulted in low levels of an
      FpQ/U/K-spliced transcript. However, there was a large increase of FpQ- and FpQ/U
      spliced transcripts with unknown 3' sequences. Furthermore, a new transcript,
      initiated at an unidentified site 5' of the BamHI f/K cleavage site and
      continuing through BamHI K into the EBNA1-encoding K exon without interruption,
      was produced in substantial amounts in the lytic cycle.

PMID- 10073709
TI  - Activation in vivo of retroperitoneal fibromatosis-associated herpesvirus, a
      simian homologue of human herpesvirus-8.
AB  - Retroperitoneal fibromatosis-associated herpesvirus of rhesus macaques (RFHVMm)
      is a gammaherpesvirus closely related to human herpesvirus-8 (HHV-8), which is
      thought to be a necessary cofactor for the development of Kaposi's sarcoma (KS)
      in humans. Here, RFHVMm infection of rhesus macaques exposed to the D-type
      retrovirus simian retrovirus-2 (SRV-2) is described. Development of SRV-2
      viraemia, infection with simian immunodeficiency virus or administration of
      cyclosporin A could result in persistent RFHVMm viraemia. From this, it is
      concluded that productive retrovirus infection or otherwise-induced immune
      suppression has the ability to activate this herpesvirus in vivo. Elevated levels
      of circulating interleukin-6, a cytokine that plays a central role in KS, were
      found in RFHVMm-viraemic animals. In viraemic animals, RFHVMm was found in
      tissues that are common sites for the development of AIDS-associated KS,
      especially the oral cavity. Together, these data suggest a common biology between
      RFHVMm infection of macaques and HHV-8 infection and pathogenesis in humans.

PMID- 10073710
TI  - Immunological control of a murine gammaherpesvirus independent of CD8+ T cells.
AB  - Adult thymectomized C57 BL/6J mice were depleted of T cell subsets by MAb
      treatment either prior to, or after, respiratory challenge with murine
      gammaherpesvirus-68. Protection against acute infection was maintained when
      either the CD4+ or the CD8+ T cell population was greatly diminished, whereas the
      concurrent removal of both T cell subsets proved invariably fatal. The same
      depletions had little effect on mice with established infection. The results
      indicate firstly that both CD4+ and CD8+ T cells play a significant part in
      dealing with the acute infection, and secondly that virus-specific antibody
      contributes to controlling persistent infection with this gammaherpesvirus.

PMID- 10073711
TI  - Expression and structural characterization of a baculovirus ecdysteroid UDP
      glucosyltransferase.
AB  - The baculovirus enzyme ecdysteroid UDP-glucosyltransferase (EGT) disrupts the
      hormonal balance of the insect host by catalysing the conjugation of
      ecdysteroids, the moulting hormones, with the sugar moiety from UDP-glucose or
      UDP-galactose. In this study, EGT has been overproduced using a recombinant
      Autographa californica nucleopolyhedrovirus and an antiserum has been raised
      against the purified protein. This antiserum was used to visualize the kinetics
      of expression of EGT by wild-type AcMNPVL-1 and by the overproducing recombinant
      virus. The inclusion of tunicamycin during these time-course experiments
      suggested that EGT is glycosylated. This was confirmed by Endo F treatment, which
      showed that glycosylation increased the apparent subunit molecular mass by
      approximately 11 kDa. These sugars do not appear to be required for enzyme
      activity. EGT activity invariantly elutes from gel-filtration columns as a single
      peak corresponding to a 260 kDa (+/-50 kDa) protein. This suggests that the
      enzyme is an oligomer of three to five subunits, since the subunit molecular mass
      is 56 kDa.

PMID- 10073712
TI  - Characterization of the interaction between the baculovirus ssDNA-binding protein
      (LEF-3) and putative helicase (P143).
AB  - LEF-3 and P143 are two of six proteins encoded by the Autographa californica
      multinucleocapsid nucleopolyhedrovirus genome which are required for DNA
      replication in transient replication assays. LEF-3 has the properties of an ssDNA
      binding protein and P143 exhibits amino acid sequence homology to helicases. In
      this report, the interaction of LEF-3 and P143 was studied by yeast two-hybrid
      and immunoaffinity analyses. Using the yeast two-hybrid system, the interaction
      domain of LEF-3 (385 aa) was mapped to amino acids between positions 1 and 165.
      Deletion analysis of P143 failed to reveal an interaction domain, suggesting that
      there were either multiple interaction domains or that the deletions disrupted
      the secondary structures required for the interaction between LEF-3 and P143.

PMID- 10073713
TI  - Adaptation of the geminivirus bean yellow dwarf virus to dicotyledonous hosts
      involves both virion-sense and complementary-sense genes.
AB  - Bean yellow dwarf virus (BeYDV) and maize streak virus (MSV) belong to the
      geminivirus genus Mastrevirus and have host ranges confined to dicotyledonous and
      monocotyledonous species, respectively. To investigate viral determinants of host
      range specificity, chimeras were constructed by exchanging their coding and non
      coding regions. BeYDV chimeras containing MSV ORF V1, ORF V2 or small intergenic
      region sequences, either individually or in various sequential combinations,
      replicated and produced virus particles in Nicotiana tabacum protoplasts. BeYDV
      chimeras containing MSV ORFs C1 and C2 and/or the large intergenic region were
      unable to replicate. None of the chimeras was able to systemically infect either
      N. benthamiana or maize. Complementation experiments using BeYDV chimeras
      containing MSV ORF V1 and/or ORF V2 suggest that expression of MSV movement
      protein and/or coat protein prevents BeYDV movement. The results demonstrate that
      factors involved in both viral DNA replication and virus movement are exclusively
      adapted to either monocotyledonous or dicotyledonous host backgrounds.

PMID- 10073714
TI  - Tissue tropism related to vector competence of Frankliniella occidentalis for
      tomato spotted wilt tospovirus.
AB  - The development of tomato spotted wilt tospovirus (TSWV) infection in the midgut
      and salivary glands of transmitting and non-transmitting thrips, Frankliniella
      occidentalis, was studied to elucidate tissue tropism and the virus pathway
      within the body of this vector. Immunohistological techniques used in this study
      showed that the midgut, foregut and salivary glands were the only organs in which
      virus accumulated. The first signals of infection, observed as randomly
      distributed fluorescent granular spots, were found in the epithelial cells of the
      midgut, mainly restricted to the anterior region. The virus subsequently spread
      to the circular and longitudinal midgut muscle tissues, a process which occurred
      late in the larval stage. In the adult stage, the infection occurred in the
      visceral muscle tissues, covering the whole midgut and foregut, and was abolished
      in the midgut epithelium. The infection of the salivary glands was first observed
      72 h post-acquisition, and simultaneously in the ligaments connecting the midgut
      with these glands. The salivary glands of transmitting individuals appeared
      heavily or completely infected, while no or only a low level of infection was
      found in the glands of non-transmitting individuals. Moreover, the development of
      an age-dependent midgut barrier against virus infection was observed in second
      instar larvae and adults. The results show that the establishment of TSWV
      infection in the various tissues and the potential of transmission seems to be
      regulated by different barriers and processes related to the metamorphosis of
      thrips.

PMID- 10073715
TI  - Experimentally induced bovine spongiform encephalopathy did not transmit via goat
      embryos.
AB  - Goats are susceptible to experimental challenge with bovine spongiform
      encephalopathy (BSE). This study set out to investigate whether the transmission
      of BSE could occur in goats following the transfer of embryos from experimentally
      infected donor females into uninfected recipient females. The results showed no
      evidence of transmissible spongiform encephalopathy disease in any of the
      offspring which developed from embryos from infected donors, nor indeed in any of
      the recipient females used as surrogate dams. In addition, there was no
      indication of experimental BSE spreading as either a venereal infection to males
      used in mating or by maternal transmission to offspring born naturally to
      experimentally infected donors, although numbers were small.

PMID- 10073716
TI  - The public understanding of vaccination.

PMID- 10073718
TI  - Attempt to modify the immune response developed against FIV gp120 protein by
      preliminary FIV DNA injection.
AB  - Following inactivated virus vaccination trials, the surface glycoprotein gp120
      (SU) of the feline immunodeficiency virus (FIV) was considered as one of the
      determinants for protection. However, several vaccination trials using
      recombinant Env protein or some Env-derived peptides failed to induce protection.
      To study the influence of the environment in which the surface protein (SU) is
      injected. we analyzed the impact of a nucleocapsid (NC) DNA immunization on the
      presentation of the recSU protein to the immune system. Cats were vaccinated
      either with the recSU protein alone or with NC DNA followed by the recSU protein.
      Two routes of nucleocapsid DNA vaccination were tested: intramuscular and mucosal
      injections. Cats immunized with the recSU protein showed a facilitation of
      infection, since they presented the earliest and the highest humoral response
      correlating with the highest proviral load. They also showed an acceleration of
      the appearance of IL4 mRNA signal. Preliminary injection of the DNA coding for NC
      protein, regardless the route of inoculation, seemed to inhibit the facilitation
      induced by vaccination with the recSU protein alone. The previously nucleocapsid
      DNA immunized cats had infectious status similar to those of the control cats,
      but with lower proviral load and less developed anti-FIV humoral response. Cat
      No. 2, belonging to the group vaccinated with NC protein by the mucosal route,
      had a protected-like status which did not correlate with the humoral response.
      This cat was the only one to have a persisting IFN mRNA signal after challenge
      specific for the p10 nucleocapsid and recSU proteins. However, no NC specific
      cytotoxic cells were observed throughout the experiment in this cat. The role of
      nucleocapsid DNA vaccination is still unknown nevertheless we did demonstrate
      that the facilitation observed in vaccination trial with recombinant proteins
      could be modified and that recombinant proteins could be a component of an
      effective vaccine.

PMID- 10073717
TI  - The serum albumin-binding region of streptococcal protein G (BB) potentiates the
      immunogenicity of the G130-230 RSV-A protein.
AB  - BBG2Na is a protein comprising residues 130-230 of the respiratory syncytial
      virus subgroup A (RSV-A) G protein (G2Na) fused to the albumin-binding domain of
      streptococcal G protein (BB). BBG2Na was cloned, expressed in Escherichia coli
      and renaturated. In rodent models, this subunit RSV vaccine adjuvanted in
      Alhydrogel induced specific antibodies and conferred protection to RSV infection.
      Comparison of the antibody production in a BALB/c mouse model revealed that
      BBG2Na induced a stronger and earlier G2Na antibody response than G2Na alone,
      without altering the IgG subclass distribution. To address the role of the BB
      part, we explored its carrier properties and showed that it is a Th dependent
      antigen, generating a more potent G2Na-specific B cell memory response and able
      to generate Th cells that provide help for G2Na antibody production.

PMID- 10073719
TI  - The effect of smoking on influenza, influenza vaccination efficacy and on the
      antibody response to influenza vaccination.
AB  - We examined the relation between cigarette smoking and (1) the occurrence of
      influenza, (2) the efficacy of influenza vaccination and (3) the antibody
      response to influenza vaccination in fifteen family practices in South-Limburg,
      the Netherlands, during the influenza season 1991 1992. Data were used from a
      randomized double-blind placebo-controlled trial into the efficacy of influenza
      vaccination in which smoking status was measured 10 weeks after the start of the
      trial. A total of 1838 subjects aged 60 years or older, of whom 1531 subjects
      (321 smokers, 1152 non-smokers and 58 cigar/pipe smokers) who returned the
      smoking questionnaire and were not previously vaccinated, were used in the
      analyses. The main outcome measures were serological influenza (fourfold increase
      of antibody titre between 3 weeks and 5 months after vaccination); clinical
      influenza as determined by criteria of the Dutch Sentinel Stations from self
      reported symptoms in postal questionnaires 10 weeks and 5 months after
      vaccination; increases after vaccination and decreases after 5 months in
      logarithmic titres of antibody against the vaccine strains. No relation between
      smoking and either serological or clinical influenza was found, although the risk
      for serological influenza was slightly (not significantly) elevated in smokers
      compared to non-smokers. A statistical interaction was found between smoking and
      vaccination when serological influenza was the outcome measure indicating that
      the efficacy of vaccination was greater in smokers than in non-smokers
      (comparison of model with and without interaction; likelihood ratio test, p <
      0.0001). This finding is supported by a greater titre rise 3 weeks after
      vaccination for two out of four strains, but not by the antibody response after
      vaccination in previous studies on influenza and other infectious diseases. Also,
      this possible difference of immunogenicity is not reflected in a better
      protection for clinical influenza. The rise in antibody titre 3 weeks after
      vaccination was higher in smokers for A/Singapore/6/86 and B/Beijing/11/87, but
      not for the other two strains. Decline in titres after 5 months was similar for
      smokers and non-smokers. We conclude that smoking has no clinical or preventive
      significance for risk of influenza in the elderly.

PMID- 10073720
TI  - An experimental marker vaccine and accompanying serological diagnostic test both
      based on envelope glycoprotein E2 of classical swine fever virus (CSFV).
AB  - Envelope glycoprotein E2 is the most immunogenic protein of classical swine fever
      virus (CSFV). In a proposed model of the antigenic structure of E2, the N
      terminal half of E2 forms two independent structural antigenic units, A and BC.
      E2 without transmembrane region (E2-TMR) is expressed and secreted into the
      medium of insect cells by use of the baculovirus expression system. The immune
      response induced by E2 protects pigs against CSFV. Recently, we showed that the
      protective immune response to a homologous CSFV challenge can be induced by a
      single unit, A or BC, of E2. An indirect blocking ELISA, or complex trapping
      blocking assay (CTB) based on both units is routinely used worldwide for
      serological diagnosis of CSFV infections. Here we show that E2-TMR is secreted
      into the medium as a homodimer. This E2 homodimer was used to develop a CTB
      detecting antibodies directed against one immunogenic unit of E2. Thus, the
      protective immune response induced by E2 containing one unit was not detected
      with a modified CTB based on the other unit, whereas immune responses induced by
      a variety of low virulent CSFV strains were detected with such a modified CTB.
      These results indicate that a deletion E2 protein in combination with a modified
      CTB are feasible as CSF marker vaccine and accompanying differentiating
      diagnostic test.

PMID- 10073721
TI  - Immunogenicity of Actinobacillus ApxIA toxin epitopes fused to the E. coli heat
      labile enterotoxin B subunit.
AB  - Peptides KDYGASTGSSL (Epil). SLLRRRRNGEDVSV (Epi3) and DDEIYGNDGHP (Epi6),
      predicted to constitute immunogenic epitopes of the hemolysin-cytotoxin ApxIA of
      Actinobacillus pleuropneumoniae were inserted into a surface-exposed loop of the
      B subunit of the E. coli heat-labile enterotoxin (EtxB). The resulting chimeric
      proteins were recognized by monospecific antibodies against purified native ApxI
      and by convalescent sera of pigs that were positive for A. pleuropneumoniae
      serotype 1. Mice anti-sera against chimeric proteins EtxB::ApxIAEpi3 and
      EtxB::ApxIAEpi6 reacted with purified ApxI. These results indicate that Epi3 and
      Epi6 regions constitute linear epitopes of the structural ApxIA protein toxin.
      Epitope Epi6 which is located in the structure of the glycine rich repeats in
      ApxI elicits the formation of hemolysin neutralizing antibodies when introduced
      into mice in the form of a chimeric EtxB fusion protein. We suggest that fusion
      of peptide sequences to EtxB is a useful tool for the analysis of epitopes of
      complex proteins such as RTX toxins.

PMID- 10073722
TI  - A single dose of an effective whole cell pertussis vaccine does not significantly
      increase protection in children primed with a less effective vaccine.
AB  - We evaluated if a single dose of a protective whole cell pertussis vaccine given
      before school entry to children primed with a less effective vaccine would
      increase their protection. A school cohort including 3876 students and a family
      cohort including 162 children were assessed. Although there was a trend toward
      increased protection. the better vaccine did not provide a significant
      improvement. These results suggest that a single dose of an effective vaccine
      given to children primed with a less effective one does not raise the protection
      to at level similar to that provided by three doses of the better vaccine.

PMID- 10073723
TI  - Protection against experimental infection with group B streptococcus by
      immunization with a bivalent protein vaccine.
AB  - Group B streptococcus (GBS), a bacterium with polysaccharide capsule, is the
      major cause of sepsis and meningitis in early infancy. Recent work has indicated
      that immunity to GBS infection can be elicited by the surface proteins Rib and
      alpha, either of which is expressed by most GBS strains causing invasive
      infections. Here we show that a bivalent vaccine, composed of purified Rib and
      alpha mixed with aluminum hydroxide (alum), an adjuvant accepted for human use,
      elicits an antibody response to each of the two antigens. Moreover, the bivalent
      vaccine was found to protect against experimental infection with GBS strains
      representing the four classical serotypes. Our results represent an encouraging
      step towards the development of a human GBS vaccine based on pure protein
      antigens.

PMID- 10073724
TI  - Vaccination of mice with DNA plasmids coding for the Chlamydia trachomatis major
      outer membrane protein elicits an immune response but fails to protect against a
      genital challenge.
AB  - A DNA plasmid encoding the gene of the major outer membrane protein (MOMP) of the
      Chlamydia trachomatis mouse pneumonitis (MoPn) serovar and three plasmids
      containing the variable domains (VD) of the MOMP were constructed. Female mice
      were inoculated with the plasmids and 60 days later were challenged in the
      genital tract with C. trachomatis. Six weeks after challenge female mice were
      caged with male mice and the course of the mating followed. Mice immunized with
      the MOMP plasmids mounted weak humoral and cell mediated immune responses.
      However, following the genital challenge no significant differences in vaginal
      shedding were observed between the groups immunized with the MOMP and control
      plasmids. In addition, the fertility rates were similar in the experimental and
      negative control groups. In conclusion, vaccination with DNA plasmids encoding
      the MOMP elicited a modest immune response but did not protect against infection
      or disease.

PMID- 10073725
TI  - A randomised, double-blind, controlled trial of a killed L. major vaccine plus
      BCG against zoonotic cutaneous leishmaniasis in Iran.
AB  - Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed
      with BCG against zoonotic cutaneous leishmaniasis was tested in healthy
      volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side
      effects were similar in both groups but tended to be slightly more frequent and
      prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration >
      or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2%
      vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative
      incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%).
      However, LST responders on day 80 (> or =5 mm) had a significantly lower
      incidence (35%) of CL during the first year than non-responders. A single dose of
      ALM + BCG is not sufficiently immunogenic to provide a measurable response when
      compared to BCG alone. A single dose of this vaccine has been shown to be safe
      with no evidence of an exacerbating response following natural infection; hence,
      multiple doses or other adjuvants should be considered to increase its
      immunogenicity.

PMID- 10073726
TI  - DNA inoculations with HIV-1 recombinant genomes that express cytokine genes
      enhance HIV-1 specific immune responses.
AB  - Vaccination with HIV-1 DNA sequences induce both humoral and cellular immune
      responses in experimental animals. However, these responses are relatively weak
      and are often only transient in their nature. In order to enhance the level of
      HIV-1 specific immunity, we have engineered HIV-1 DNA constructs which contained
      various cytokine genes such as interleukin-2 (IL-2), granulocyte-macrophage
      colony stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) gene. These
      constructs have deleted the tat and nmf genes of HIV-1 to eliminate their
      immunosuppressive effects. Immunizations with these recombinant constructs
      elicited moderate proliferative T cell responses but poor antibody responses in
      rats. However, inoculations of HIV-1 DNA that contained the GM-CSF or the IL-2
      gene significantly enhanced humoral and proliferative T cell responses,
      respectively. Thus, recombinant HIV-1 genomes such as those described here may
      increase the efficacy of DNA vaccination.

PMID- 10073727
TI  - High susceptibility of Mongolian gerbil (Meriones unguiculatus) to Borna disease
      virus.
AB  - Borna disease virus (BDV) is a neurotropic enveloped virus with a nonsegmented,
      single-, negative-stranded RNA genome. This virus induced encephalitis in
      experimentally infected adult rats, but in newborn rats BDV established a
      persistent, tolerant infection with no apparent clinical signs. Here, we report
      evidence that newborn Mongolian gerbils (Meriones unguiculatus) are more
      susceptible to experimental intracranial inoculation of horse-derived BDV in
      persistently infected MDCK cells, compared with similar inoculation in newborn
      rats. All inoculated newborn gerbils, but not rats, died 30 days after infection.
      Reverse transcriptase-polymerase chain reaction amplified BDV-specific sequences
      in several regions including the brain. Histopathological analysis revealed
      apparent inflammatory reactions in the brains of inoculated gerbils but not rats,
      although similar levels of BDV RNA were detected in both gerbil and rat brains.
      BDV-specific antigen and RNA were identified predominantly in neurons in the
      brains by immunohistochemistry with antibodies to BDV and in situ hybridization
      with BDV-specific riboprobes, respectively. BDV in the gerbil brain was easily
      rescued by co-cultivation of the brain homogenate with human oligodendroglioma
      cells. Thus, gerbils seem to be a useful animal model for studying BDV-induced
      pathogenesis in the brain.

PMID- 10073728
TI  - IL-6 induces long-term protective immunity against a lethal challenge of
      influenza virus.
AB  - The coadministration of cytokines can modulate immunity in DNA based viral
      vaccines. In order to determine the effects of various cytokines on long-term
      protection against the influenza virus, mice were intramuscularly coinoculated
      with plasmids that encoded either the granulocyte-macrophage colony-stimulating
      factor (GMCSF), interleukin-4 (IL-4), interleukin-12 (IL-12), or the interleukin
      6 (IL-6) gene, in the presence of two plasmids that encoded the nucleoprotein
      (NP) and the hemagglutinin (HA) gene of the influenza A virus. The
      coadministration of IL-4, IL-6 and IL-12 transiently enhanced antibody responses
      against influenza virus in early time points (4 to 7 week post immunization)
      after post inoculation. The expression of GMCSF gene resulted in the sustained
      elevation of antibody responses for at least 20 weeks post inoculation. However,
      NP-specific CTL responses decreased in these animals. Mice that received either
      the IL-12 or the IL-6 gene had enhanced NP-specific CTL responses. Remarkably,
      the coadministration of the IL-6 gene completely protected mice from a lethal
      challenge with influenza virus. Conversely, mice that received the IL-4 gene
      appeared to be more susceptible to lethal challenge than mice that were
      inoculated with the NP and the HA genes alone. These results demonstrate that the
      use of cytokines as molecular adjuvants when coadministered in influenza DNA
      vaccination must be specific. Our data also demonstrates that the
      coadministration of IL-6 should be considered to enhance the efficacy of
      influenza DNA vaccines.

PMID- 10073729
TI  - Immunization with recombinant Semliki Forest virus induces protection against
      influenza challenge in mice.
AB  - The replicon of Semliki Forest virus (SFV) offers the possibility to direct high
      level, transient expression of heterologous proteins in vivo. We initiated
      studies to determine the possibility of employing the SFV expression system for
      recombinant vaccine purposes. Mice immunized with recombinant SFV encoding
      Influenza A nucleoprotein (NP) or E. coli LacZ developed long-lasting antigen
      specific IgG levels and induction of cytotoxic T-cell (CTL) memory that persisted
      for over one year. Predominantly type 1 T-helper cells were induced as shown by
      IgG subclass ELISA. Humoral and cell-mediated immune responses could be induced
      upon delivery by several administration routes and mucosal immunizations induced
      secretory IgA in the respiratory tract. Development of immune responses against
      the vector itself did not inhibit boost responses by subsequent immunizations
      with recombinant SFV. Immunization of mice with vectors encoding the Influenza A
      virus antigens nucleoprotein (NP) and hemagglutinin (HA) resulted in immune
      responses that were protective against challenge infection with Influenza virus.

PMID- 10073730
TI  - Comparing immunogenicity of two measles, mumps and rubella vaccines.

PMID- 10073731
TI  - Drug discovery and development in the molecular era.

PMID- 10073732
TI  - How will knowledge of the human genome affect drug therapy?

PMID- 10073733
TI  - Clinical pharmacology and drug regulation.

PMID- 10073734
TI  - The use of atypical antipsychotics in the management of schizophrenia.
AB  - Long-term drug treatment of schizophrenia with conventional antipsychotics has
      limitations: an estimated quarter to one third of patients are treatment
      resistant; conventional antipsychotics have only a modest impact upon negative
      symptoms (poverty of thought, social withdrawal and loss of affect); and adverse
      effects, particularly extrapyramidal symptoms (EPS). Newer, so-called atypical,
      antipsychotics such as olanzapine, risperidone, sertindole and clozapine (an old
      drug which was re-introduced in 1990) are claimed to address these limitations.
      Atypical agents are, at a minimum, at least as effective as conventional drugs
      such as haloperidol. They also cause substantially fewer extrapyramidal symptoms.
      However, some other adverse effects are more common than with conventional drugs.
      For example, clozapine carries a significant risk of serious blood disorders, for
      which special monitoring is mandatory; it also causes troublesome drowsiness and
      increased salivation more often than conventional agents. Some atypical agents
      cause more weight gain or QT prolongation than older agents. The choice of
      therapy is, therefore, not straightforward. At present, atypical agents represent
      an advance for patients with severe or intolerable EPS. Most published evidence
      exists to support the use of clozapine, which has also been shown to be effective
      in schizophrenia refractory to conventional agents. However, the need for
      compliance with blood count monitoring and its sedative properties make careful
      patient selection important. The extent of any additional direct benefit offered
      by atypical agents on negative symptoms is not yet clear. The lack of a depot
      formulation for atypical drugs may pose a significant practical problem. To date,
      only two double-blind studies in which atypical agents were compared directly
      have been published. Neither provides compelling evidence for the choice of one
      agent over another. Atypical agents are many times more expensive than
      conventional drugs. Although drug treatment constitutes only a small proportion
      of the costs of managing schizophrenia, the additional annual cost of the use of
      atypical agents in, say, a quarter of the likely U.K. schizophrenic population
      would be about 56 M pound sterling. There is only limited evidence of cost
      effectiveness. Atypical antipsychotics are not currently licensed for other
      conditions where conventional antipsychotics are commonly used, such as behaviour
      disturbance or dementia in the elderly. Their dose, and place in treatment in
      such cases have yet to be determined.

PMID- 10073735
TI  - The therapeutic monitoring of antimicrobial agents.
AB  - AIMS: To review the basis and optimal use of therapeutic drug monitoring of
      antimicrobial agents. METHODS: Antimicrobial agents for which a reasonable case
      exists for therapeutic drug monitoring were reviewed under the following
      headings: pharmacokinetics, why monitor, therapeutic range, individualisation of
      therapy, sampling times, methods of analysis, interpretative problems and cost
      effectiveness of monitoring. RESULTS: There is a strong historical case for
      monitoring aminoglycosides. The recent move to once-daily dosing means that
      criteria for therapeutic drug monitoring need to be redefined. Vancomycin has
      been monitored routinely but many questions remain about the most appropriate
      approach to this. A case can be made for monitoring teicoplanin, flucytosine and
      itraconazole in certain circumstances. CONCLUSIONS: The approach to monitoring
      aminoglycosides needs to be redefined in the light of once-daily dosing. It is
      premature to suggest that less stringent monitoring is necessary as toxicity
      remains a problem with these drugs. The ideal method of monitoring vancomycin
      remains to be defined although a reasonable case exists for measuring trough
      concentrations, mainly to ensure efficacy. Teicoplanin is monitored occasionally
      to ensure efficacy while flucytosine is monitored occasionally to avoid high
      concentrations associated with toxicity. Itraconazole has various pharmacokinetic
      problems and monitoring has been suggested to ensure that adequate concentrations
      are achieved.

PMID- 10073736
TI  - Comparison of urinary 6beta-hydroxycortisol/cortisol ratio between neonates and
      their mothers.
AB  - AIMS: To assess CYP3A enzyme activity in human neonates by measuring the urinary
      6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio. METHODS: Fifty-six mature
      male neonates with normal delivery, seventeen of their mothers and twenty-four
      healthy non-pregnant young women participated in this study. Urinary 6beta-OHF/C
      ratio was determined on the day of birth in neonates and their mothers. In
      addition, changes in the ratio after birth were determined in neonates. RESULTS:
      On the day of birth, the urinary 6beta-OHF/C ratio of neonates was significantly
      higher than that of their mothers (20.5 vs 6.9). In contrast, no significant
      difference was observed in the mean ratio of urinary 6beta-OHF/C between women
      with and without pregnancy (6.9 vs 9.0). The urinary 6beta-OHF/C ratio after
      birth was decreased day by day in neonates. CONCLUSION: These results indicate
      that the high urinary 6beta-OHF/C ratio in mature neonates on the day of birth is
      independent of the activity of CYP3A enzyme in their mothers.

PMID- 10073737
TI  - Binding of propofol to blood components: implications for pharmacokinetics and
      for pharmacodynamics.
AB  - AIMS: Propofol is a widely used i.v. anaesthetic agent. However, its binding
      properties to blood components have not been fully studied. METHODS: We studied
      the binding of propofol to erythrocytes, to human serum and to isolated serum
      proteins. Because propofol bound to ultrafiltration and equilibrium dialysis
      membranes, we used a co-binding technique with dextran coated charcoal and with
      erythrocytes. RESULTS: Propofol free fraction in blood was 1.2-1.7% at total
      concentrations ranging from 2.80 to 179 microM (0.5 to 32 microg ml(-1)). Fifty
      percent was bound to erythrocytes and 48% to serum proteins, almost exclusively
      to human serum albumin. In the clinical range of concentrations (0.5-16 microg
      ml(-1)) 40% of the molecules bound to erythrocytes are on the red blood cells
      membranes. No binding to lipoproteins occurred and binding to alpha1-acid
      glycoprotein was less than 1.5% CONCLUSIONS: We conclude that hypoalbuminaemia
      may increase propofol free fraction particularly during prolonged administration.
      Since propofol is non-restrictively cleared, no change in clearance is expected
      to occur, and the increase in free fraction will not be compensated by a parallel
      increase in clearance. It is also noted that many in vitro studies used
      concentrations 50 to 500 times the concentration expected to be encountered in
      the immediate cellular environment.

PMID- 10073738
TI  - Pharmacokinetics of flutamide in patients with renal insufficiency.
AB  - AIMS: The aim of this study was to determine the pharmacokinetic parameters of
      flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically
      active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD)
      clearance of flutamide and hydroxyflutamide was also determined. METHODS:
      Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26
      male subjects with normal renal function (creatinine clearance by 24 h urine
      collection, CLcr, greater than 80 ml min(-1) 1.73 m(-2); n=6) or reduced renal
      function; CLcr=50-80 (n=7), 30-49 (n=3), 5-29 (n=4), and <5 ml min(-1) 1.73 m(-2)
      HD (n=6), following a single, oral 250 mg flutamide dose. Subjects undergoing HD
      received a second 250 mg dose of flutamide 4 h prior to HD; blood and dialysate
      were collected during HD to determine dialysability of flutamide and
      hydroxyflutamide. RESULTS: Cmax, tmax, AUC, t1/2, and renal clearance of
      flutamide and hydroxyflutamide did not differ between groups. Less than 1% of the
      dose appeared in dialysate as hydroxyflutamide. No serious adverse events were
      observed. CONCLUSIONS: Renal function did not affect flutamide nor
      hydroxyflutamide disposition. HD did not alter hydroxyflutamide pharmacokinetics.
      Dosing adjustments for renal impairment or HD are not indicated for flutamide.

PMID- 10073739
TI  - A study of the relative bioavailability of cysteamine hydrochloride, cysteamine
      bitartrate and phosphocysteamine in healthy adult male volunteers.
AB  - AIMS: Cysteamine, the only drug available for the treatment of cystinosis in
      paediatric patients, is available as the hydrochloride, the bitartrate and as
      sodium phosphocysteamine salts. It has been suggested that cysteamine bitartrate
      and phosphocysteamine are better tolerated and may have a better bioavailability
      than cysteamine hydrochloride. This has, however, never been demonstrated.
      METHODS: We compared the pharmacokinetics and tolerance of these three
      formulations of cysteamine in 18 healthy adult male volunteers in a double-blind,
      latin-square, three-period, single oral dose cross-over relative bioavailability
      study. RESULTS: No statistical difference was found between relative
      bioavailabilities, AUC (0, infinity) (geometric mean and s.d. in micromol l(-1)
      h: 169+/-51, 158+/-46, 173+/-49 with cysteamine hydrochloride, phosphocysteamine
      and cysteamine bitartrate respectively), Cmax (geometric mean and s.d. in
      micromol l(-1); 66+/-25.5, 59+/-12, 63+/-20) and tmax (median and range in h:
      0.88 (0.25-2), 1.25 (0.25-2), 0.88 (0.25-2)) with each of the three forms of
      cysteamine tested. Bioequivalence statistics (90% confidence intervals) showed
      non equivalence of Cmax of cysteamine base as the only non equivalence of
      pharmacokinetics between the three formulations: 90% CI for Cmax relative ratios
      to cysteamine hydrochloride were [75.6-105.81 for phosphocysteamine and [74.2
      124.2] for cysteamine bitartrate. The only significant adverse event was vomiting
      whose frequency was inversely correlated with body weight (Spearman's r=-0.76,
      P<0.001). The nature of the salt tested did not influence vomiting. CONCLUSIONS:
      While none of the three forms of cysteamine tested has a clear advantage over the
      others in terms of pharmacokinetics and tolerance profile, this should now
      however be addressed in patients treated for cystinosis during repeat
      administrations.

PMID- 10073740
TI  - The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel
      linear and nonlinear elimination.
AB  - AIMS: To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor
      GI198745 (dutasteride) to allow for more accurate predictions of GI198745
      concentrations after different dosing schedules. METHODS: In this randomized,
      single-blind, parallel group study, 32 healthy male volunteers received single
      oral doses of GI198745 ranging from 0.01 to 40 mg. Data were analysed by
      nonlinear mixed effects modelling using NONMEM where both linear and nonlinear
      pharmacokinetic models were examined. RESULTS: The time course of GI198745 serum
      concentrations indicated concentration dependent elimination, with the apparent
      half-life increasing with dose. Data were best described by a two-compartment
      model with first order absorption and parallel linear and nonlinear elimination
      pathways. Drug absorption was rapid, and was followed by a short distribution
      phase. A high volume of distribution (511 l) and a low linear clearance (0.58 l
      h(-1)) combined to give a half-life of up to 5 (1-7) weeks at high
      concentrations. As concentrations declined towards Km (0.96 ng ml(-1)), the
      proportion eliminated by the relatively rapid saturable elimination pathway, with
      a maximum clearance of 6.2 l h(-1), increased and the half-life reduced to about
      3 days. The estimated inter individual variability for the linear clearance was
      high (CV = 70%). CONCLUSIONS: G1198745 pharmacokinetics are well described by a
      pharmacokinetic model with parallel linear and nonlinear elimination. Simulations
      using this model show that at daily doses of 0.1 mg the steady state drug
      concentrations, and the rate at which these are achieved, are mainly influenced
      by the nonlinear pathway, while at daily doses above 1 mg they are almost
      entirely influenced by the linear pathway.

PMID- 10073741
TI  - Ketotifen and cardiovascular effects of xamoterol following single and chronic
      dosing in healthy volunteers.
AB  - AIMS: To study whether desensitization occurs after long-term administration of
      the 1-adrenoceptor partial agonist xamoterol and, if so, whether this can be
      influenced by ketotifen. METHODS: In a double-blind, randomized design 10 young,
      healthy males received ketotifen (2 x 1 mg day(-1) p.o.) or placebo for 3 weeks
      with xamoterol (2 x 200 mg day(-1) p.o.) administered concomitantly during the
      last 2 weeks. 'l1-adrenoceptor mediated responses were assessed as exercise
      induced tachycardia and isoprenaline-induced shortening of heart rate corrected
      electromechanical systole (QS2c); isoprenaline-induced tachycardia was measured
      as a mixed beta1-/beta2-adrenoceptor-mediated effect. RESULTS: The first dose of
      xamoterol significantly increased resting heart rate and systolic blood pressure
      and significantly shortened QS2c. The last dose of xamoterol after 2 weeks of
      treatment still produced the same responses. Ketotifen did not influence these
      effects of xamoterol on resting haemodynamics. The first dose of xamoterol caused
      a rightward shift of the exercise- and isoprenaline-induced tachycardia (mean
      dose ratios+/-s.e.mean: 1.20+/-0.05 and 2.46+/-0.23) and the isoprenaline-evoked
      shortening of QS2c (dose ratio 3.59+/-0.68). This rightward shift was even more
      pronounced after 2 weeks xamoterol treatment. This additional rightward shift
      after 2 weeks of xamoterol was not affected by ketotifen (mean difference (95%
      CI) of log transformed dose ratios between placebo and ketotifen: exercise
      tachycardia 0.001 (-0.03; 0.04); isoprenaline tachycardia 0.03 (-0.15; 0.21);
      isoprenaline induced shortening of QS2c 0.13 (-0.22; 0.48)). CONCLUSIONS: In
      humans xamoterol is a partial beta1-adrenoceptor agonist with positive chrono-
      and inotropic effects at rest and antagonistic properties under conditions of
      beta-adrenoceptor stimulation. These effects were well maintained after chronic
      dosing with no signs of beta1-adrenoceptor desensitization. Ketotifen does not
      change the beta-adrenoceptor mediated responses of xamoterol after chronic
      dosing.

PMID- 10073743
TI  - Vasoconstriction in human isolated middle meningeal arteries: determining the
      contribution of 5-HT1B- and 5-HT1F-receptor activation.
AB  - AIMS: Sumatriptan is a 5-HT1B/1D-receptor agonist which also has affinity for 5
      HT1F-receptors. The vasoconstrictor effects of sumatriptan are thought to be 5
      HT1B-receptor mediated and these receptors have been shown to be expressed in
      human cranial blood vessels. However, in the same tissue mRNA coding for 5-HT1F
      receptors has also been identified and this study addresses the possibility of
      whether 5-HT1F-receptor activation contributes to vasoconstriction. METHODS: The
      ability of two selective 5-HT1B/1D-receptor antagonists (GR125,743 and GR127,935)
      with no affinity for 5-HT1F-receptors, to inhibit sumatriptan evoked contractions
      in human isolated middle meningeal artery was investigated. Using a series of 5
      HT1B/1D-receptor agonists (sumatriptan, zolmitriptan, CP122,288, L-741,519 and L
      741,604), some with high affinity for 5-HTIF-receptors and the non-selective 5-HT
      receptor agonists 5-HT and 5-CT, we compared the vasoconstrictor potency of these
      drugs in human isolated middle meningeal artery with their affinities at cloned
      human 5-HT1B-, 5-HT1D-and 5-HT1F-receptors expressed in CHO cell lines. RESULTS:
      GR125,743 antagonized sumatriptan evoked contractions in a competitive manner
      (apparent pA2 9.1) and GR127,935 antagonized sumatriptan-induced responses in a
      non-competitive manner (reducing the maximum contraction to 27%). There was a
      significant correlation between vasoconstrictor potency and 5-HT1B-receptor
      affinity (r=0.93, P=0.002) but not with 5-HT1D- or 5-HT1F-receptor affinity
      (r=0.74, P=0.06; r= 0.31, P= 0.49, respectively). CONCLUSIONS: These experiments
      show that in human middle meningeal artery vasoconstriction to sumatriptan-like
      agents is 5-HT1B-receptor mediated with little if any contribution from 5-HT1F
      receptor activation.

PMID- 10073742
TI  - Differential vascular alpha1-adrenoceptor antagonism by tamsulosin and terazosin.
AB  - AIMS: In patients with lower urinary tract symptoms suggestive of benign
      prostatic obstruction the alpha1-adrenoceptor antagonist terazosin lowers blood
      pressure whereas only very small if any alterations were reported with the alpha1
      adrenoceptor antagonist tamsulosin. Therefore, we have compared the vascular
      alpha1-adrenoceptor antagonism of tamsulosin and terazosin directly. METHODS: Ten
      healthy subjects were investigated in a randomized, single-blind, three-way cross
      over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or
      placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5
      h after drug intake, alterations of diastolic blood pressure and other
      haemodynamic parameters in response to a graded infusion of the alpha1
      adrenoceptor agonist phenylephrine were determined non-invasively. RESULTS: At
      most time points tamsulosin inhibited phenylephrine-induced diastolic blood
      pressure elevations significantly less than terazosin (5 h time point: median
      difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand,
      phenylephrine-induced changes of cardiac output, heart rate and stroke volume
      were similar during both active treatments. CONCLUSIONS: In doses equi-effective
      for treatment of lower urinary tract symptoms tamsulosin causes less inhibition
      of vasoconstriction than terazosin.

PMID- 10073744
TI  - The effects of age on human venous responsiveness to neuropeptide Y.
AB  - AIMS: Neuropeptide Y (NPY) is a sympathetic neurotransmitter released with
      noradrenaline during sympathetic stimulation. Ageing has been shown to be
      associated with a reduction in alpha2 and beta-adrenoceptor mediated responses in
      veins, but it is not known whether NPY responsiveness is also altered with
      increasing age. METHODS: Using a dorsal hand vein technique, we examined NPY
      receptor responsiveness in 24 normal, healthy subjects (20-72 years; 10 males, 14
      females). Graded infusions of NPY (25-2000 pmol min(-1)) were administered (5 min
      at each dose) into a dorsal hand vein. Venous distension at 45 mmHg was measured
      at 3-5 min of each infusion. Dose-response curves to NPY were constructed and the
      peak venoconstriction was calculated. RESULTS: Dose-dependent venoconstriction
      was seen in all but one subject. The peak venoconstriction observed with NPY was
      significantly and negatively correlated with the age of the normal subjects (r=
      0.63, P<0.01). When subjects were ranked from youngest to oldest and divided into
      tertiles, (20-40 years, n = 8; 41-55 years, n = 8; 56-72 years, n = 8), mean dose
      response curves were different with the oldest tertile being significantly less
      responsive (P<0.05). The peak venoconstriction observed (% of control) was 65.1+/
      7.0, 46.5+/-9.4, and 24.4+/-4.8%, respectively. The oldest tertile had a
      significantly decreased peak venoconstriction compared with the youngest tertile
      (P<0.01). Infusion of NPY into a dorsal hand vein had no systemic effects on
      heart rate or blood pressure in any of the subjects studied. CONCLUSIONS: Hand
      vein responsiveness to exogenously infused NPY in normal subjects is decreased as
      age increases. The reduction of NPY-receptor-mediated responses with age may
      influence sympathetic nervous system control of the venous system with advancing
      age.

PMID- 10073745
TI  - Role of nitric oxide in isoprenaline and sodium nitroprusside-induced relaxation
      in human hand veins.
AB  - AIMS: Recent reports, largely in animal models, have suggested that either
      inhibition of nitric oxide (NO) synthase or endothelium removal in arteries
      inhibits the response to isoprenaline, a beta-adrenoceptor agonist, and also
      enhances the response to sodium nitroprusside, a nitrovasodilator. This in vivo
      study was designed to determine whether N(G)-monomethyl-L-arginine (L-NMMA), an
      inhibitor of NO synthesis, influences relaxation of human hand veins mediated by
      isoprenaline or by sodium nitroprusside. METHODS: Using the dorsal hand vein
      technique, full dose-response curves to bradykinin (0.27-278 ng min(-1), n=6),
      isoprenaline (2.12-271 ngmin(-1), n=8) and sodium nitroprusside (0.01-634 ng min(
      1) n=7) were generated on separate occasions before and after L-NMMA co-infusion
      (50 microg min(-1)). RESULTS: In veins preconstricted with the alpha1
      adrenoceptor-selective agonist phenylephrine, the three vasodilators induced
      maximal responses (Emax) of 119+/-35, 72+/-18 and 103+/-17%, respectively. L-NMMA
      inhibited relaxation to bradykinin by 64% (P=0.014) but did not influence
      relaxation induced by isoprenaline. The sensitivity to sodium nitroprusside was
      significantly enhanced by L-NMMA co-infusion (concentration shift of 2.3,
      P=0.031). CONCLUSIONS; We conclude that in human veins, spontaneously released NO
      does not play a major role in isoprenaline-induced relaxation. Our results also
      suggest that the effects of sodium nitroprusside in this vascular bed may be
      attenuated by endothelium-derived NO.

PMID- 10073746
TI  - A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and
      simvastatin in normal clinical practice using the New Zealand Intensive Medicines
      Monitoring Programme (IMMP).
AB  - AIMS: Because of the importance of treating dyslipidaemia in the prevention of
      ischaemic heart disease and because patient selection criteria and outcomes in
      clinical trials do not necessarily reflect what happens in normal clinical
      practice, we compared outcomes from bezafibrate, gemfibrozil and simvastatin
      therapy under conditions of normal use. METHODS: A random sample of 200 patients
      was selected from the New Zealand Intensive Medicines Monitoring Programme's
      (IMMP) patient cohorts for each drug. Questionnaires sent to prescribers
      requested information on indications, risk factors for ischaemic heart disease,
      lipid profiles with changes during treatment and reasons for stopping therapy.
      RESULTS: 80% of prescribers replied and 83% of these contained useful
      information. The three groups were similar for age, sex and geographical region,
      but significantly more patients on bezafibrate had diabetes and/or hypertension
      than those on gemfibrozil or simvastatin. After treatment and taking the initial
      measure into account, the changes in serum lipid values were consistent with
      those generally observed, but with gemfibrozil being significantly less effective
      than expected. More patients (15.8%S) stopped gemfibrozil because of an
      inadequate response compared with bezafibrate (5.4%) and simvastatin (1.6%).
      Gemfibrozil treatment was also withdrawn significantly more frequently due to a
      possible adverse reaction compared with the other two drugs. CONCLUSIONS: In
      normal clinical practice in New Zealand gemfibrozil appears less effective and
      more frequently causes adverse effects leading to withdrawal of treatment than
      either bezafibrate or simvastatin.

PMID- 10073747
TI  - Record-linkage for pharmacovigilance in Scotland.
AB  - Record-linkage is the linkage of patient-specific information that is stored
      separately. Recent advances in computerization have meant that record-linkage
      techniques in medical research are increasingly being used and refined. In
      particular, they have made a significant contribution to pharmacovigilance, which
      involves linking drug exposure to outcomes data. In this article, the
      contribution of record-linkage in Scotland to medical research is described. The
      two organizations that utilize record-linkage techniques are the Medicines
      Monitoring Unit (MEMO) of the University of Dundee and the Information and
      Statistics Division (ISD) of the NHS in Scotland. Pharmacovigilance is MEMO's
      main concern (using data from the Tayside region of Scotland), while ISD link
      health care datasets for Scotland for general health care research. The
      experience of the two groups is now being combined to carry out drug safety
      studies in the entire population of Scotland.

PMID- 10073748
TI  - Cough and angiotensin II receptor antagonists: cause or confounding?
AB  - AIMS: Cough is one of the most frequent side effects associated with angiotensin
      converting enzyme inhibitors (ACEIs) but is not thought to be associated with
      losartan, an angiotensin II receptor antagonist (ARA). This study compares
      reports of cough with losartan and three ACEIs used in general practice. METHODS:
      Studies have been conducted for losartan, and three ACEIs enalapril, lisinopril
      and perindopril, using the technique of Prescription-Event Monitoring. Patients
      were identified using dispensed prescription data. Questionnaires were sent to
      patients' general practitioners 6 months after the date of first prescription.
      Cases of cough within the first 60 days of treatment with losartan resulting in
      withdrawal of the drug were followed up with additional questionnaires. Incidence
      rates for reports of cough were calculated. In order to reduce the impact of
      carry-over effects, rate ratios were calculated for first reports of cough
      between days 8 and 60 using losartan as the index drug. RESULTS: The cohort for
      each drug exceeded 9000 patients. Age and sex distributions and indications for
      prescribing the four drugs were similar. Cough was the most frequent reason for
      discontinuation of losartan and the most frequently reported event in the first
      month of treatment with this drug. When reports of cough between days 1-7 were
      excluded, rates of cough were significantly higher for the three ACEIs when
      compared with losartan (rate ratios 1.5, 4.8 and 5.7, all P<0.03). 101 patients
      had discontinued losartan due to cough. 91% of these had previously been
      prescribed an ACEI and 86% had previously experienced ACEI cough. CONCLUSIONS:
      Carry-over accounted for the observed excess of reports of cough with losartan.
      Rates of cough between days 8 and 60 were significantly higher for the three
      ACEIs compared with losartan. Confounding factors associated with comparative
      observational cohort studies are discussed.

PMID- 10073749
TI  - Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping:
      possible effect of age, liver disease and length of therapy.
AB  - AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a
      marker for polymorphic CYP2C19 activity in a Japanese population of healthy young
      subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy
      subjects were administered a single dose of omeprazole (20 mg), whereas patients
      received 20 mg daily for at least 1 week. The ratio of the serum concentration of
      omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a
      measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant
      alleles associated with the poor metaboliser phenotype of (S)-mephenytoin,
      CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in
      the initial codon were analysed. RESULTS: In the healthy volunteer study there
      was complete concordance between genotype and phenotype. However, eight of the
      patients who had the EM genotype had a high value for their hydroxylation index,
      and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were
      detected in the eight mismatched patients. They were all genotypic heterozygous
      EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired
      CYP2C19 activity combined with partial saturation of omeprazole metabolism during
      multiple dosing may have contributed to the discrepancy between CYP2C19
      genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead
      of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be
      reliable enough for clinical application in Japanese patients.

PMID- 10073750
TI  - CYP2D6 polymorphism in a Gabonese population: contribution of the CYP2D6*2 and
      CYP2D6*17 alleles to the high prevalence of the intermediate metabolic phenotype.
AB  - AIMS: To determine the molecular basis of the intermediate extensive metaboliser
      (EM) CYP2D6 phenotype in healthy Gabonese subjects. METHODS: The CYP2D6 phenotype
      of 154 healthy Gabonese subjects was assessed by giving the subject a single dose
      of 30 mg dextromethorphan, and collecting their urine for the next 8 h. The
      CYP2D6 genotype was determined for 50 individuals of the EM phenotypic group by
      Southern blotting and various PCR-based procedures aimed at identifying different
      CYP2D6 alleles. RESULTS: We found that in the studied Gabonese population, as
      compared with a French population, there is significantly higher frequency of
      intermediate EM phenotype having lower frequency of CYP2D6 PM alleles. To clarify
      this discrepancy phenotype-genotype relationship was studied. We found that the
      CYP2D6*17 and CYP2D6*2 alleles, prevalent in this black population, are
      characterised by their low capacity for dextromethorphan demethylation. Our data
      also show that the CYP2D6*1 allele is associated with the highest in vivo
      activity followed by the CYP2D6*2 allele and then the CYP2D6*17 allele.
      CONCLUSIONS: The higher frequencies of the CYP2D6*2 and CYP2D6*17 alleles than
      the CYP2D6*1 allele account for the high frequency of the intermediate EM
      phenotype in this black population. The polymorphism of the CYP2D6 enzyme
      activity in African populations could have important implications for use of
      drugs that are substrates for CYP2D6 and have a narrow therapeutic window.

PMID- 10073751
TI  - Pathogenesis of mycotic aneurysms.

PMID- 10073752
TI  - Assessing arterial inflow before infrainguinal bypass grafting.

PMID- 10073753
TI  - Options in the surgical management of aorto-iliac occlusive disease: a changing
      perspective.
AB  - The numerous options available for the treatment of aortoiliac occlusive disease
      have led to controversy over which is best. Not only are the technical aspects of
      direct aortoiliac reconstruction debated but the role of lower risk but less
      durable options such as extraanatomic bypass and balloon angioplasty and/or
      stenting is still unsettled. Rather than yield to the tendency to apply one
      method preferentially over the others, it is important to realize that each
      approach has a selective role to play in the overall management of aortoiliac
      occlusive disease, if applied in appropriate settings. In discussing these
      applications, the history of these controversies, and the pros and cons of each
      competitive approach are reviewed, along with the results of experiences with
      them by the author and others. While it is apparent that outcome data, stratified
      for location, and degree and extent of the occlusive disease being treated, are
      still needed for proper comparisons of some competitive techniques, especially
      balloon angioplasty and stenting, there is sufficient evidence to make certain
      general recommendations: endarterectomy should be limited to younger patients
      with soft atheromatous disease of the lower aorta and proximal iliac arteries; a
      femoral distal anastamosis is preferable to one at the iliac bifurcation; choice
      of proximal anastamosis should be based on the distribution of aortoiliac
      occlusive disease; concomitant profundaplasty is effective only if significant
      profunda narrowing is present (and not simply superficial femoral artery
      occlusion); the need for concomitant distal bypass can and should be predicted;
      axillobifemoral bypass should be limited to patients with 'prohibitive' risk or
      'hostile' abdominal pathology; and, in view of the low risk and good long term
      patency of unilateral iliac bypasses, iliac PTA and stenting should not be
      extended to category III and IV lesions without demonstrating superior long term
      results for such lesions.

PMID- 10073754
TI  - Superficial femoral artery endarterectomy: tried...but not tested?

PMID- 10073755
TI  - Source of elastin-degrading enzymes in mycotic aortic aneurysms: bacteria or host
      inflammatory response?
AB  - Elastolytic matrix metalloproteinases play a central role in the development of
      chronic atherosclerotic aortic aneurysms, but mycotic aortic aneurysms are a
      distinct and unusual form of aneurysm disease caused by bacterial infection.
      Mycotic aortic aneurysms follow a more rapid and unpredictable course than
      chronic aneurysm disease and they exhibit a predilection for the suprarenal
      aorta, further implying unique pathophysiologic mechanisms. The purpose of this
      study was to examine the nature and source of elastin-degrading enzymes in
      mycotic aortic aneurysm. Bacterial isolates and aortic tissues were obtained from
      four consecutive patients undergoing surgical repair of suprarenal mycotic aortic
      aneurysm. Using an in vitro 3H-labeled elastin degradation assay, elastin
      degrading enzyme activity was only observed in the bacteria-conditioned medium
      from an isolate of Pseudomonas aeruginosa. Elastin-degrading enzyme activity in
      the aortic tissue homogenate of this patient was abolished by the serine protease
      inhibitor, phenylmethylsulfonyl fluoride, but it was not suppressed by the
      metalloproteinase inhibitor, ethylenediamine tetraacetic acid (EDTA). In
      contrast, elastin-degrading enzyme activity in the bacterial-conditioned medium
      was decreased by about half by both phenylmethylsulfonyl fluoride and EDTA.
      Elastin substrate zymography revealed two phenylmethylsulfonyl fluoride
      inhibitable elastin-degrading enzyme activities in the aortic tissue homogenate
      that corresponded to human neutrophil elastase (approximately 30 kDa) and its
      stable complex with alpha 1-proteinase inhibitor (approximately 80 kDa), but no
      activity attributable to Pseudomonas elastase, a 33-kDa metal-dependent enzyme.
      Human neutrophil elastase was readily detected throughout mycotic aortic aneurysm
      tissues by immunohistochemistry, but elastolytic metalloproteinases were only
      occasionally observed. The results of this study suggest that the elastin
      degrading enzyme produced in mycotic aortic aneurysm are largely serine proteases
      of host neutrophil origin, rather than elastases produced by the infecting
      microorganisms or the macrophage-derived metalloproteinases typically observed in
      atherosclerotic aneurysm disease. Further studies will be needed to extend these
      findings to a larger number of patients with mycotic aortic aneurysm and those
      caused by additional microorganisms.

PMID- 10073756
TI  - The value and limitations of magnetic resonance angiography of the circle of
      Willis in patients undergoing carotid endarterectomy.
AB  - Magnetic resonance angiography is a useful technique to determine the patency of
      the circle of Willis when compared with conventional four-vessel angiography. The
      purpose of this study is to determine whether the integrity of the circle of
      Willis, assessed by magnetic resonance angiography, provides adequate collateral
      cerebral circulation during carotid endarterectomy and correlates with internal
      carotid artery back pressure. Over a recent 20-month period, 35 patients were
      studied preoperatively with magnetic resonance angiography of the carotid
      bifurcations of the circle of Willis and the vertebrobasilar system. All patients
      underwent standard carotid endarterectomy with intraoperative measurement of
      internal carotid artery back pressure. Patients with an internal carotid artery
      back pressure < 50 mmHg had an intraluminal shunt placed. Deficiencies in
      branches of the circle of Willis, the carotid bifurcation and the vertebrobasilar
      system determined by magnetic resonance angiography were correlated with internal
      carotid artery back pressure using Fisher's exact test. Only one patient had a
      completely intact circle of Willis. Eleven of 16 patients (69%) who had an
      internal carotid artery back pressure < 50 mmHg had an occluded A1 segment of the
      anterior cerebral artery combined with an occluded posterior communicating
      artery, whereas only five of 19 patients (26%) who had an internal carotid artery
      back pressure > 50 mmHg had similar findings (P < 0.03). Severity of occlusive
      disease of the contralateral internal carotid artery and the basilar artery did
      not independently predict internal carotid artery back pressure. An occluded
      anterior branch of the circle of Willis in combination with an occluded posterior
      branch of the circle of Willis is associated with an internal carotid artery back
      pressure < 50 mmHg. Although magnetic resonance angiography of the circle of
      Willis may provide valuable anatomic information, it is not sufficiently accurate
      to predict the need for carotid shunting and therefore its use cannot be
      justified on a routine basis.

PMID- 10073757
TI  - Microemboli detected by transcranial Doppler monitoring in patients during
      carotid angioplasty versus carotid endarterectomy.
AB  - Microemboli, as detected by transcranial Doppler monitoring, have been shown to
      be a potential cause of strokes after carotid endarterectomy. We retrospectively
      reviewed 105 patients who underwent transcranial Doppler monitoring during 112
      procedures for the treatment of 115 carotid bifurcation stenoses: 40 by
      percutaneous angioplasty with stenting and 75 by carotid endarterectomy. In PTAS
      procedures (n = 40), there was a mean of 74.0 emboli per stenosis (range 0-398, P
      = 0.0001) with 4 neurologic events per patient (P = 0.08). In CEA procedures (n =
      76), there was a mean of 8.8. emboli per stenosis (range 0-102, P= 0.0001) with 1
      neurologic event per patient (P = 0.08). The post-procedural neurological events
      in the percutaneous angioplasty with stenting population included two strokes
      (5.6%) and two transient ischemia attacks (5.6%). Microemboli for each of these
      cases totalled 133, 17, 29 and 47 (with one shower), respectively. One
      postoperative carotid endarterectomy patient was noted to have a stroke (1.4%),
      with 48 microemboli noted during that procedure. The mean emboli rate for
      percutaneous angioplasty with stenting patients with neurological events was
      59.0: without complications it was 85.1. The mean emboli rate for carotid
      endarterectomy patients without complications was 8.3. Three percutaneous
      angioplasty with stenting patients had no emboli (7.5%), whereas 29 carotid
      endarterectomy patients had no emboli (38.7%). CONCLUSION: The percutaneous
      angioplasty with stenting procedure is associated with more than eight times the
      rate of microemboli seen during carotid endarterectomy when evaluated with
      transcranial Doppler monitoring. Larger patient groups are needed to determine if
      this greater embolization rate has an associated risk of higher morbidity or
      mortality.

PMID- 10073758
TI  - The use of low-dose heparin is safe in carotid endarterectomy and avoids the use
      of protamine sulfate.
AB  - Controversy exists concerning the appropriate dose of heparin needed during
      carotid endarterectomy. Use of high-dose heparin (100 U/kg) during carotid
      endarterectomy may require the use of protamine to minimize perioperative
      bleeding complications. At the authors' institution the use of 30 U/kg heparin
      for arterial reconstruction has obviated the need for protamine. A retrospective
      study of carotid endarterectomies performed was undertaken. Patients undergoing
      combined procedures with carotid endarterectomy were excluded. A total of 420
      carotid endarterectomies were performed in 330 patients. All received 3000 U of
      heparin or less during carotid endarterectomy. Non-fatal stroke and transient
      neurological deficits occurred in 0.48% and 1.9%, respectively. Mortality was
      0.9%. Wounds were dry in 97%, swollen in 2.5% and bloody in 0.5%. No patient
      received protamine. Two patients were returned to the operating room for re
      exploration because of hematoma. In conclusion, the use of protamine may be
      safely avoided with 30 U/kg heparin, and give acceptable stroke- and minimal
      complication rates.

PMID- 10073759
TI  - Asymptomatic carotid artery stenosis associated with peripheral vascular disease:
      a prospective study.
AB  - This study aimed to determine the prevalence of symptomless internal carotid
      artery stenosis in consecutive patients presenting with peripheral vascular
      disease. Duplex ultrasound screening of the carotid arteries was used to
      determine the degree of stenosis. Co-morbidities were recorded together with age,
      sex and tobacco use. Internal carotid artery stenosis of > 50% was found in 35%
      of patients. Among these there was > or = 70% stenosis in 18% of patients and of
      this group 5% had an occluded carotid vessel at first presentation. Males
      presented with peripheral vascular disease and associated carotid stenoses at a
      younger age than females. Male smokers had a higher prevalence of stenosis (P =
      0.036) but all smokers had developed stenoses 3-5 years before non-smokers.
      Females with abdominal aortic aneurysms had a greater prevalence of carotid
      stenosis (P = 0.037), and male aneurysmal disease diminished stenosis prevalence
      (P = 0.023). Men with an elevated serum creatinine were more likely to have a
      stenosis (P = 0.019), but not women. The other co-morbidities were not
      specifically associated with carotid artery stenosis.

PMID- 10073760
TI  - The results of routine primary closure in carotid endarterectomy.
AB  - PURPOSE OF STUDY: The aims of this study were to determine the incidence of
      restenosis following carotid endarterectomy with primary closure of the
      arteriotomy and to observe the natural history of disease progression in the 1st
      postoperative year. METHODS: The study group consisted of a consecutive series of
      126 patients undergoing carotid endarterectomy. Duplex imaging was performed
      preoperatively and at 8 weeks, 6 months and 1 year postoperatively. RESULTS: Five
      patients (4%) had a residual stenosis. At 12 months, the overall restenosis rate
      was 15%: 8.5% for males and 28.9% for females. None of these restenoses were
      symptomatic. There was no significant difference in the diameter of the internal
      carotid artery between male and female patients (U = 896, P = 0.60) and no
      significant difference in the diameter of the arteries that had restenosed at 12
      months and those that had remained patent (U = 391, P = 0.33). CONCLUSIONS:
      Carotid endarterectomy with primary closure is associated with a low incidence of
      restenosis in men, but not in women. Criteria for selective patching should
      consider both gender and vessel calibre.

PMID- 10073761
TI  - Poor outcome in patients aged over 80 with limb-threatening ischaemia.
AB  - The aim of this study was to determine the outcome in a consecutive series of
      patients over 80 years of age with limb-threatening ischaemia. The authors
      performed a retrospective case-note review of the treatment and outcome in 108
      patients with 131 episodes of leg ischaemia, who presented to a vascular unit
      between 1992-1996 inclusively. Some 73 (56%) episodes of leg ischaemia occurred
      in patients suitable for active treatment (limb salvage 75%, amputation 4% and
      death 21%). Results were inferior in patients not actively treated (limb salvage
      19%, amputation 50% and death 31%). Elderly patients not selected for active
      treatment have a very poor outcome and are seldom mentioned in publications. In
      future, clinical reports should include actively treated and rejected patients to
      avoid selection bias. Research should focus on the selection process and
      alternative therapies.

PMID- 10073762
TI  - Reconstruction for lower limb occlusive disease in the elderly.
AB  - OBJECTIVES: To determine the acceptability of performing distal limb bypass for
      occlusive vascular disease in the over 75's. METHOD: Patients undergoing surgery
      between January 1988 and December 1996 were included. Data were obtained from a
      card system, operating ledgers, admission diaries and hospital notes. RESULTS: A
      total of 166 patients were identified. There were 69 women and 97 men, 79 were
      aged 75-79 years, 81 were 80-89 years and six older than 90 years. A total of 171
      procedures were performed: infrainguinal bypass in 131 (77%), aorto-femoral
      bifurcation grafts in 10 (6%) and extra-anatomic bypass in 30 (17%). This
      represents 28.1% of all reconstructions for occlusive disease during this time.
      Nine patients (5.4%) died within 30 days and one (0.6%) required a major
      amputation. During the follow-up period (median 12 months), 14 major and 10 minor
      amputations were required. Ten patients underwent a second successful
      reconstructive procedure. CONCLUSION: Reconstruction in this group of older
      patients can be carried out with acceptable 30-day mortality and limb salvage
      rates.

PMID- 10073763
TI  - Justification of intervention for limb-threatening ischemia: a surgical decision
      analysis.
AB  - Intervention for vascular occlusive disease of the distal lower extremity in
      elderly patients will inevitably be scrutinized as medical resources decline. The
      authors applied surgical decision analysis to three treatment options:
      revascularization, amputation and expectant management. The appropriate outcome
      probabilities were derived from our experience with revascularization to the
      tibial and pedal vessels, and utility scores were obtained by formalized patient
      assessment. Revascularization was predicted to improve patient outcome by 1.10
      quality-adjusted life-years compared with primary amputation and by 1.16 quality
      adjusted life-years compared with expectant management. To gain one additional
      quality-adjusted life-years, revascularization would cost $5280 more than
      expectant management, but $33,900 less than primary amputation. Sensitivity
      analysis predicted revascularization to be the least costly treatment per quality
      adjusted life-years as long as 1-month patency exceeds 11%. Revascularization for
      limb-threatening ischemia of the distal lower extremity is justified and can be
      performed at a reasonable cost.

PMID- 10073764
TI  - Assessing arterial inflow before infra-inguinal bypass grafting: a survey of the
      members of the Vascular Surgical Society of Great Britain and Ireland.
AB  - The optimal assessment of arterial inflow is controversial. We investigated
      current preferences of inflow assessment prior to infra-inguinal bypass grafting.
      A questionnaire was sent to 364 members of the Vascular Surgical Society of Great
      Britain and Ireland asking about inflow assessment in different clinical
      situations, access to resources, size of hospital and number of grafts performed
      each year. Questionnaires analysed = 169. Angiography was used by 89.5%, most
      single view. Two views angiography was used more often by surgeons performing
      more than 20 femoro-distal grafts each year (79.3 versus 37.6%). Routine use of
      iliac duplex was < 20%; poor femoral pulse increased this to near 30%. About 90%
      of respondents had access to colour flow duplex. Most respondents use single
      plane angiography to assess inflow before infra-inguinal grafting. Two views and
      functional tests are used more commonly by surgeons working in larger or teaching
      hospitals and those performing more grafts.

PMID- 10073765
TI  - Vascular surgery without arteriography: use of Duplex ultrasound.
AB  - Although contrast arteriography has served as the historical 'gold standard' for
      diagnosis of arterial disease, recent improvements in noninvasive diagnostic
      methods have made it possible to plan surgical treatment without subjecting
      patients to this invasive procedure. This approach avoids both the risks and
      costs associated with arteriography. Duplex scanning has become the standard
      noninvasive test for extracranial carotid artery disease, and it can also be used
      to directly evaluate the lower extremity arteries. In addition to the standard
      duplex criteria for classification of carotid stenosis, new criteria are
      available that reflect the stenosis thresholds identified in randomized clinical
      trials. Clinical experience has clearly shown that carotid endarterectomy can be
      performed safely based on the duplex scan alone in the majority of patients:
      however, arteriography is still indicated in selected cases. The evaluation of
      lower extremity arterial disease requires examination of multiple arterial
      segments, and most vascular surgeons still rely on the anatomic detail provided
      by arteriography for preoperative planning. Still, it may be possible to avoid
      formal preoperative arteriography in selected patients by using a combination of
      lower extremity duplex scanning and intraoperative arteriography. Further
      developments in noninvasive testing will continue to reduce the need for
      diagnostic arteriography prior to direct arterial surgery.

PMID- 10073766
TI  - Surgical intervention in venous ulceration.
AB  - The purpose of this article is to review surgical management for dermal
      ulceration that results from chronic venous insufficiency. Efficacy is gauged by
      freedom from recurrent ulceration, an objective clinical monitor. Accurate
      preoperative diagnosis and postoperative assessment of the venous circulation is
      enhanced by reliable non-invasive examinations. A recently developed clinical
      classification unifies reporting criteria and has been widely subscribed.
      Standard surgical ablation of incompetent saphenous and other superficial veins
      significantly improves clinical and hemodynamic outcome. Perforator incompetence
      alone is rarely the cause of ulcerative disease, but adjunctive ligation of
      communicating veins is considered important to the effective elimination of
      chronic venous insufficiency. New endoscopic techniques reduce morbidity
      associated with long incisions from the open subfascial procedure. In a more
      advanced role, deep venous reconstruction is infrequently performed, but is quite
      durable. Free-tissue transfer appears to be effective after 2 years of
      observation. Post-thrombotic chronic venous insufficiency continues to confer a
      more severe prognosis, which emphasizes the importance of accurate and precise
      diagnosis. Investigation of patients with ulcerative chronic venous insufficiency
      should be actively pursued, since individualized surgical management will
      effectively reduce recurrence of ulceration.

PMID- 10073767
TI  - Insulin like growth factor-1 activates nuclear factor-kappaB and increases
      transcription of the intercellular adhesion molecule-1 gene in endothelial cells.
AB  - A critical early event in the pathogenesis of occlusive vascular disease is the
      adhesion of monocytes to endothelial cells. The authors have previously reported
      that insulin-like growth factor-1 increases monocyte-endothelial cell adhesion
      and increases the expression of intercellular adhesion molecule-1. In this study,
      it is hypothesized that the upregulation of intercellular adhesion molecule-1
      expression after treatment with insulin-like growth factor-1 is caused by an
      increase in the transcription of intercellular adhesion molecule-1 in endothelial
      cells, and that this transcription is regulated, at least in part, by activation
      of nuclear factor-kappaB. Adherence cell assays were performed using insulin-like
      growth factor-1 treated human umbilical vein endothelial cells and human
      monocytes. To determine the role of nuclear factor-kappaB, Western blotting using
      the anti-p65 (activated portion of nuclear factor-kappaB) was performed on cell
      lysate of human umbilical vein endothelial cells treated with insulin-like growth
      factor-1. RT-PCR was performed on RNA extracted from insulin-like growth factor-1
      treated human umbilical vein endothelial cells. Intercellular adhesion molecule-1
      antibody attenuated the increase in monocyte-endothelial cell adhesion of
      endothelial cells exposed to insulin-like growth factor-1. We observed an
      increase in expression of the activated nuclear factor-kappaB p65 protein in
      response to insulin-like growth factor-1 treatment. Peak increase occurred at 30
      min. This effect was sensitive to pretreatment of human umbilical vein
      endothelial cells with the insulin-like growth factor-1 receptor antibody. Human
      umbilical vein endothelial cells treated with insulin-like growth factor-1 for 2
      and 4 h revealed a significant increase in intercellular adhesion molecule-1 mRNA
      as compared with untreated human umbilical vein endothelial cells. Tumor necrosis
      factor-alpha produced a larger increase in intercellular adhesion molecule-1 mRNA
      expression. These results suggest that insulin-like growth factor-1 enhances
      intercellular adhesion molecule-1 transcription and activates nuclear factor
      kappaB in endothelial cells. The intracellular pathways that increase cell
      adhesion molecule expression may provide a common link to understanding the
      monocyte-endothelial cell adhesion that occurs in the early stages of
      atherosclerosis and restenosis.

PMID- 10073768
TI  - Genetic tracing of arterial graft flow surface endothelialization in allogeneic
      marrow transplanted dogs.
AB  - In order to trace genetically the source of fallout endothelialization on
      arterial grafts, six beagle dogs with successful autologous bone marrow
      transplantation received composite tandem aortic grafts with an isolated, totally
      impervious Dacron graft and a porous Dacron graft for 12 weeks. For impervious
      segments, five of 12 fresh tissue samples were Factor VIII/von Willebrand factor
      + (FVIII/vWF) and seven had faint or negative signals; three of the FVIII/vWF +
      samples had alpha-actin + smooth muscle cells. Polymerase chain reaction (PCR)
      study showed eight had a pure donor DNA genotype and four had donor/host mixed,
      with the donor predominant. Of 12 AgNO3-stained samples, 11 showed pure donor
      type and one had donor/host mixed, with the donor predominant. For porous
      segments, all 12 fresh samples had positive flow surface FVIII/vWF and alpha
      actin cells. PCR showed all these samples and all 12 AgNO3-stained samples had
      donor/host mixed type, but the host pattern was predominant. Porous graft healing
      appears to involve both cellular fallout and tissue ingrowth, and bone-marrow
      derived cells may be a source for fallout.

PMID- 10073769
TI  - Cerebral blood flow and oxygen metabolism during cardiopulmonary bypass with
      moderate hypothermic selective cerebral perfusion.
AB  - Cerebral blood flow was measured using transcranial doppler during
      cardiopulmonary bypass in nine patients with selective cerebral perfusion for
      surgery of arch aorta (group S). For comparison, 11 adult open heart patients
      (group C) were also measured. The authors' selective cerebral perfusion at 28
      degrees C resulted in moderate hypothermia and antegrade perfusion using
      independent pumps for three branches. Total flow in the three branches was 500
      ml/min. A Labodop DP-100 doppler ultrasound velocimeter was used to measure
      middle cerebral arterial blood flow velocity. Hemoglobin concentration and oxygen
      saturation were also measured in arterial and jugular venous blood. The
      arteriovenous oxygen content difference (Ca-vO2) was calculated and multiplied by
      the middle cerebral arterial blood flow velocity value, which resulted in the
      cerebral metabolic rate for oxygen (CMRO2). The cerebral perfusion pressure of
      group S was lower than in group C, and the arterial carbon-dioxide tension
      (PaCO2) of group S was higher than in group C during cardiopulmonary bypass.
      Middle cerebral arterial blood flow velocity values of both groups remained
      constant before, during and after cardiopulmonary bypass. The CMRO2 decreased
      during cardiopulmonary bypass and showed no difference between the two groups.
      The changes in PaCO2 might be significant factors in the increase in cerebral
      blood flow during selective cerebral perfusion. This study supports the
      conclusion that, compared with our routine open heart surgery procedures, our
      selective cerebral perfusion procedures had the same cerebral blood flow and
      oxygen metabolism during cardiopulmonary bypass.

PMID- 10073770
TI  - Estimation of intraoperative aortocoronary bypass saphenous vein graft
      circumference from its preoperative compliance.
AB  - The aim of this study was to determine if the intraoperative circumference of
      aortocoronary saphenous vein bypass grafts could be predicted from preoperative
      measurement with B-mode ultrasound sonography in 50 patients. The circumference
      of the saphenous vein was measured during stepwise increments of a thigh
      congestive cuff from 0 to 60 mmHg. The circumference of the corresponding segment
      of the coronary bypass vein graft was measured intraoperatively with callipers.
      The intraoperative circumference was higher (11.8+/-2.3 mm) than the preoperative
      circumference (10.2+/-2.4 mm, P=0.006) matched to its corresponding
      intraoperative mean arterial pressure (57+/-15 mmHg). The prediction of the
      intraoperative circumference by estimation from the preoperative pressure
      circumference relationship fitted by a linear model (r = 0.412, P = 0.004) did
      not improve on the preoperative circumference matched by arterial pressure alone
      (r = 0.429, P = 0.003). The intraoperative circumference of the graft vein
      exceeded its preoperative circumference by 12%. Prediction of the intraoperative
      graft vein circumference is underestimated by a linear model of its preoperative
      compliance.

PMID- 10073771
TI  - 'High dose' aprotinin and heparin-coated circuits: clinical efficacy and
      inflammatory response.
AB  - Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response
      to cardiopulmonary bypass circuit, improve biocompatibility and may protect the
      postoperative hemostasic mechanisms in routine coronary bypass operations. 'High
      dose' aprotinin reduces bloodloss, transfusion needs, and re-explorations as a
      result of bleeding, and may have an additional role in reducing the inflammatory
      response of the body to cardiopulmonary bypass circuit. It has not been
      established, however, if the addition of a heparin-coated circuit to the
      intraoperative administration of 'high dose' aprotinin further reduces the whole
      body inflammatory response to cardiopulmonary bypass circuit and improves the
      postoperative clinical course of the patients who are undergoing coronary
      surgery. Thirty patients undergoing primary elective coronary artery bypass
      grafting were studied. All the patients received, intraoperatively, the serine
      protease inhibitor aprotinin according to the 'Hammersmith' protocol and full
      heparin dose. Patients were randomly allocated to be treated either with a
      circuit completely coated with surface-bound heparin (n = 15) or with an
      uncoated, but otherwise identical, circuit (n = 15). Differences in the clinical
      course of the two groups of patients, as well as differences in the behavior of
      hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein)
      factors before, during and after bypass, were analyzed. There were no significant
      differences between the two groups in terms of bleeding and transfusional
      requirements, the time spent on a ventilator, or in duration of stay in the
      intensive care unit (ICU). In all patients, a significant increase in the total
      white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred
      in relation to cardiopulmonary bypass. This was not influenced by heparin
      precoating of the circuit. In addition, there was an increase in the monocyte
      count during follow-up, and there was a trend towards higher monocyte counts in
      the patients who were treated with heparin-coated circuits. These results suggest
      that the addition of a heparin-coated circuit to the intraoperative 'high-dose'
      aprotinin therapy probably had little influence on the clinical course and on the
      time-course of the inflammatory parameters of the adult patients undergoing
      primary coronary surgery with a full heparinization protocol.

PMID- 10073772
TI  - Myocardial revascularization in patients < or = 45 years old: evaluation of
      cardial and functional capacity, and return to work.
AB  - OBJECTIVE: To investigate whether patients < or = 45 years old benefit from
      myocardial revascularization, measured by New York Heart classification,
      functional status and return to work. METHODS: The data of 188 consecutive
      patients 45 years old and younger, and who were undergoing primary isolated
      aortocoronary bypass operation, were studied. Follow-up information was obtained
      from our follow-up databank. A cross-sectional follow-up was conducted and an
      additional functional evaluation by the Duke Activity Status Index and the work
      situation. RESULTS: The follow-up, was complete for 98.2% of patients and showed
      a survival rate of 99% at 12 and 86.1% at 120 months. Eight patients died during
      follow-up. There was a significant improvement of NYHA classification. The Dukes
      Activity Status Index showed a good correlation with the NYHA class; however,
      only 47% of the patients returned to work.

PMID- 10073773
TI  - Familial carotid body paragangliomas and sensorineural hearing-loss: a new
      syndrome.
AB  - BACKGROUND: Carotid body paragangliomas are rare tumors that are sometimes
      familial, the transmission of which is thought to be by genomic imprinting. We
      have treated a family who exhibited co-inheritance of carotid body paraganglioma
      and sensorineural hearing-loss, a relationship that has not been previously
      reported. METHODS: We studied a large Australian family who exhibited familial
      carotid body paragangliomas, many of whose members also suffered tinnitus or
      hearing-loss. This relationship was examined by reviewing the medical records of
      family members with confirmed tumors, carrying out neck ultrasonic scanning or
      computed tomography on their relatives to look for previously unrecognized
      tumors, and arranging audiometric testing. This information was used to
      characterize the type of hearing-loss present in this family and to construct a
      pedigree for the two traits. RESULTS: The hearing-loss observed in this family
      was sensorineural in character. Of 15 family members studied over four
      generations, eight were confirmed positive for both carotid body paraganglioma
      and sensorineural hearing-loss, two for the tumor only (one of whom did not have
      his hearing assessed) and one for hearing-loss alone. Four family members were
      negative for both traits. CONCLUSIONS: The pedigree provides evidence of a
      previously undescribed association between familial carotid body paraganglioma
      and sensorineural hearing-loss, a combination that appears to be co-inherited in
      this family.

PMID- 10073774
TI  - Adjuvant techniques for the management of large carotid body tumors. A case
      report and review.
AB  - Although the first successful resection of a carotid body tumor was reported over
      100 years ago this operation remains technically challenging with many potential
      pitfalls. The case of a man with a large (8 cm) carotid body tumor will be
      presented in order to identify key issues that pertain to effective diagnostic
      and therapeutic modalities. A multidisciplinary team (vascular surgeon,
      neurosurgeon, neuroradiologist, interventional radiologist and oromaxillofacial
      surgeon) provided specific expertise on each aspect of the patient's evaluation
      and treatment. Adjuvant techniques employed in this case included angiographic
      tumor embolization, jaw subluxation, strap muscle division, nasotracheal
      intubation, carotid resection and saphenous vein interposition grafting.

PMID- 10073775
TI  - Functional assessment with electrocardiographic gated single-photon emission
      computed tomography improves the ability of technetium-99m sestamibi myocardial
      perfusion imaging to predict myocardial viability in patients undergoing
      revascularization.
AB  - This study evaluates the use of electrocardiographic (ECG) gated single-photon
      emission computed tomographic (SPECT) myocardial perfusion imaging for the
      prediction of viability in patients undergoing revascularization, who have
      coronary disease and left ventricular dysfunction. Fifty patients underwent
      technectium-99m (Tc-99m) sestamibi ECG gated SPECT imaging preoperatively at rest
      and 1 week after revascularization, whereas 36 (72%) also underwent imaging 6
      weeks after revascularization. Images were interpreted by the consensus of 3
      experienced readers without knowledge of patient identity or time of imaging (pre
      or postrevascularization) for perfusion and wall motion using a 17-segment
      model. Results of perfusion alone were compared with perfusion and wall motion
      combined. One hundred five coronary artery territories were revascularized, 96 of
      which were viable and 9 nonviable. Perfusion alone predicted 87 to be viable and
      18 nonviable (sensitivity 86%, specificity 55%, positive predictive value 95%,
      negative predictive value 28%, and overall accuracy 85%). Perfusion and wall
      motion combined identified 95 territories to be viable (sensitivity 95%; p
      <0.025; specificity 55%, positive predictive value 96%, negative predictive value
      50%, and overall accuracy 91%; p <0.05). Thus, Tc-99m sestamibi ECG gated SPECT
      myocardial perfusion imaging at rest allows assessment of both perfusion and wall
      motion, which significantly improves the sensitivity and overall accuracy for
      determination of viability in comparison with perfusion alone.

PMID- 10073776
TI  - Comparison of combination of dipyridamole and dobutamine during echocardiography
      with thallium scintigraphy with thallium scintigraphy to improve viability
      detection.
AB  - The aim of this study was to investigate the relation between radioisotopic and
      echocardiographic markers of myocardial viability and their correlation with
      functional recovery after coronary revascularization. Myocardial viability can be
      detected by techniques exploring various aspects of cell physiology: thallium-201
      scintigraphy and dobutamine and dipyridamole echocardiography focus on cell
      membrane integrity, beta-1 and adrenoceptor, and A2-adenosine receptor-mediated
      inotropic response, respectively. Fifty-seven patients (mean age 60+/-8 years)
      with previous myocardial infarction (>3 months), angiographically assessed
      coronary artery disease, and resting regional dysfunction underwent rest
      redistribution 201-thallium scintigraphy and low-dose pharmacologic stress echo
      with dobutamine (up to 10 microg/kg/min), very low dose regimen of dipyridamole
      (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine. Criteria for
      viability in a 13-segment model for both techniques were percent peak activity in
      redistribution images >55% for thallium-201 and a decrease in wall motion score
      >1 grade (1 [normal] to 4 [dyskinetic]) for stress echo. Thirty patients
      underwent coronary revascularization (bypass surgery in 8, angioplasty in 22) and
      were followed up at 4 weeks from intervention with a resting echocardiogram. The
      rate of agreement between thallium-201 and stress echo was 63% for dipyridamole,
      66% for dobutamine, and 74% for combined dipyridamole-dobutamine (p <0.05 vs
      dipyridamole and dobutamine). In the 30 patients who underwent revascularization,
      a regional resting dyssynergy was observed in 225 segments, assuming that
      postrevascularization functional recovery (which occurred in 126 segments) was
      the gold standard; combined dipyridamole-dobutamine showed a higher sensitivity
      (90% confidence interval [CI] 85% to 95%) than thallium-201, dobutamine, or
      dipyridamole (87%, CI 81% to 92%; 82%, CI 76% to 89%; and 82%, CI 76% to 89%,
      respectively). Specificity was lower for viability recognition with thallium-201
      (61%, CI 51% to 71%) than with dobutamine (93%, CI 88% to 98%), dipyridamole
      (95%, CI 91% to 99%), and combined dipyridamole-dobutamine (92%; CI 87% to 97%).
      Combined adrenergic and adenosinergic stimulation recruits an inotropic reserve
      in a significant proportion of segments with preserved thallium uptake that were
      nonresponders after either dipyridamole or dobutamine. When functional recovery
      after successful revascularization is considered as the postoperative gold
      standard, thallium has a higher sensitivity than dipyridamole or dobutamine; this
      sensitivity gap is filled with combined dipyridamole-dobutamine. The specificity
      of all forms of pharmacologic stress echo is better than thallium-201.

PMID- 10073777
TI  - Comparison of ramp versus step protocols for exercise testing in patients > or =
      60 years of age.
AB  - To evaluate whether individualized ramp protocols may be better than step
      protocols in patients > or = 60 years of age referred for exercise testing, peak
      cardiopulmonary responses and accuracy in prediction of oxygen uptake (VO2) for
      individualized ramp and step protocols (Bruce or modified Bruce) were compared.
      Twenty-four subjects (67+/-3 years) with known or suspected coronary artery
      disease performed both tests in random order. Protocols were selected based on
      estimated exercise capacity using a pretest activity questionnaire. No
      differences were observed between peak VO2 (19.3+/-6.3 and 19.1+/-6.4 ml/kg/min),
      heart rate (127+/-15 and 126+/-16 beats/min), rate-pressure product (24.0+/-4.8
      and 23.4+/-4.9 beats/min x mm Hg x 10(3)) and anaerobic threshold (16.6+/-3.7 and
      16.0+/-4.7 ml/kg/min) for the ramp and step protocols, respectively. The relation
      between measured submaximal VO2 and American College of Sports Medicine (ACSM)
      predicted VO2 during the ramp protocol is demonstrated by the regression
      coefficient (beta), where beta = 0.92 (95% confidence intervals [CI] 0.85 to
      0.99) and for the step protocols where beta = 1.02 (95% CI 0.84 to 1.20). Peak
      cardiopulmonary responses in the elderly are similar during individualized ramp
      and step protocols when appropriately selected based on a pretest activity
      questionnaire. Both protocols appear to provide clinically reasonable estimates
      of VO2 when gas exchange analysis is not used.

PMID- 10073778
TI  - Low-dose dobutamine testing using contrast left ventriculography in the same
      session as coronary angiography predicts the improvement of left ventricular
      function after coronary angioplasty in postinfarction patients.
AB  - The role of percutaneous transluminal coronary angioplasty (PTCA) in the subacute
      or chronic phases of myocardial infarction remains controversial. This study
      investigates the usefulness of dobutamine contrast left ventriculography in a
      single session with coronary angiography for predicting the improvement of
      ventricular function after PTCA. The study group consisted of 30 patients in whom
      a contrast left ventricular angiogram and PTCA were performed after a first
      myocardial infarction. The centerline method was used to calculate dysfunction
      extent at baseline and its variation during dobutamine infusion at 7.5
      microg/kg/min; contractile reserve was defined as a significant (> or = 15%)
      reduction of dysfunction extent. A second ventricular angiogram was performed 6
      months later in all patients. Abnormal wall motion extent decreased at 6 months
      after PTCA (84+/-21% vs 70+/-29%, p = 0.0001). Wall motion improvement after PTCA
      correlated with the response to dobutamine (r = 0.54, p = 0.002). Ten patients
      showed a significant reduction (> or = 15%) of dysfunction extent at 6 months;
      dobutamine testing had a 80% sensitivity, 84% specificity, 67% positive
      predictive value, and 89% negative predictive value in detecting regional
      function improvement. In the subgroup of 21 patients without restenosis, both the
      correlation between dysfunction improvement after PTCA and response to dobutamine
      (r = 0.72, p = 0.0001) and the accuracy of dobutamine testing (sensitivity 88%,
      specificity 92%, positive predictive value 88%, and negative predictive value
      92%) increased. The ejection fraction significantly increased (>5%) after PTCA in
      6 patients; dobutamine testing had a 67% sensitivity, 74% specificity, 44%
      positive predictive value, and 88% negative predictive value in predicting the
      increase in the ejection fraction. In the subgroup without restenosis the
      improvement of the ejection fraction correlated with the response to dobutamine
      (r = 0.63, p = 0.007), and the sensitivity of dobutamine testing was 80%,
      specificity 83%, positive predictive value 67%, and negative predictive value
      91%. In conclusion, dobutamine contrast left ventriculography testing in the same
      session as coronary angiography predicts regional function and ejection fraction
      improvement after PTCA in postinfarction patients, particularly when restenosis
      does not develop.

PMID- 10073779
TI  - Early infarct artery collateral flow does not improve long-term survival
      following thrombolytic therapy for acute myocardial infarction.
AB  - It is known that acutely developed collaterals can prevent the onset of acute
      myocardial infarction (AMI) in the presence of a total coronary occlusion.
      However, there still is controversy concerning long-term follow-up of coronary
      collateral circulation to the infarct-related artery. In this study we analyze
      the prognostic role of collateral flow (degrees 0 to 3) as well as anterograde
      flow (degrees 0 to 3) in patients with AMI treated with thrombolytic therapy.
      Four hundred twenty-two patients (median age 57 years, 355 men) with AMI were
      treated with intravenous streptokinase and followed prospectively for up to 8
      years. At the end of the study period, patients with collateral coronary flow 3
      (n = 30) and those with flow <3 (n = 392) at in-hospital coronary arteriography
      had survival rates of 66% and 85%, respectively (p <0.12). Meanwhile, patients
      with coronary anterograde flow 3 (n = 189) and those with flow <3 (n = 233) had
      survival rates of 89% and 80%, respectively (p <0.04). By censored regression
      analysis, a negative correlation was found between coronary collateral flow
      degree and survival (p = 0.0498) and, inversely, a positive correlation was found
      between coronary anterograde flow degree and survival (p = 0.0053). By Cox
      multivariate analysis, the following variables showed significant correlations
      with long-term survival: global left ventricular ejection fraction (p = 0.0003),
      anterograde flow degree (p = 0.0006), collateral flow degree (negative
      correlation, p = 0.0179), and medical treatment (negative correlation, p =
      0.0464). Thus, patients treated with intravenous streptokinase during AMI and
      with adequate coronary collateral circulation had a worse prognosis than those
      who developed adequate anterograde flow, probably because of residual myocardial
      ischemia. Such patients may benefit from coronary revascularization (angioplasty
      or surgery) to restore anterograde blood flow and minimize myocardium at risk.

PMID- 10073780
TI  - Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non
      insulin-dependent diabetes mellitus.
AB  - Microalbuminuria is an increase in urinary albumin not detected by conventional
      dipstick testing and is present in 20% of patients with non-insulin-dependent
      diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is
      60% at 8 years and is mainly due to cardiovascular disease. Because many deaths
      occur without warning symptoms, we have compared the prevalence and severity of
      silent myocardial ischemia in asymptomatic NIDDM patients with and without
      microalbuminuria. We have performed a cross-sectional, case-control study of
      asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three
      patients with microalbuminuria were matched for age, gender, diabetes duration,
      and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise
      stress test was performed and reported blind to patient status. The degree of
      electrocardiographic ST-segment depression, exercise time, work performed, and
      maximum heart rate with exercise were recorded. Patients with microalbuminuria
      had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p
      = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6
      vs 8 METs, p <0.001), and reduced age-predicted maximum heart rate (94% vs 101%,
      p = 0.004). In multiple logistic regression, albumin excretion rate was shown to
      be the strongest independent predictor of ischemic response (p = 0.03). Silent
      myocardial ischemia is common in asymptomatic NIDDM patients but is more common
      in those with microalbuminuria. In these subjects, the higher prevalence of
      ischemic response at low workloads suggests a higher probability of future
      coronary events, and possibly a higher probability of potentially treatable
      coronary artery disease.

PMID- 10073781
TI  - Initial and long-term results of angioplasty in unprotected left main coronary
      artery.
AB  - Angioplasty of the unprotected left main coronary artery (LMCA) has been
      controversial. Although recent single-center studies suggest that new devices may
      change the situation, many questions and problems remain. Therefore, the results
      of unprotected left main coronary angioplasty of 175 procedures in 107 patients
      were analyzed to evaluate its feasibility and effectiveness. The treatment of the
      initial 107 cases included balloon angioplasty (39 cases, 36%), directional
      coronary atherectomy (53 cases, 50%), and stents (15 cases, 14%). They were
      divided into 3 major subgroups: (1) acute group (n = 14), in which LMCA
      angioplasty was performed in patients with acute myocardial infarction; (2)
      emergency group (n = 10); and (3) elective group (n = 83). In-hospital mortality
      was higher in the acute (35.7%) and emergency (40.0%) groups than in the elective
      group (3.6%; p <0.0001). Angiographic follow-up was routinely performed and the
      restenosis rate including in-hospital restenosis was 70% in the acute group,
      37.5% in the emergency group, and 40% in the elective group (p = NS). The mean
      clinical follow-up period was 2.9 years, and the estimated 5-year survival rates
      of the acute and emergency groups were 50% and 48.2%, respectively. However the 5
      year survival rate of the elective group was higher than that seen in the acute
      or emergency group (77.5%; p <0.05). Repeat LMCA angioplasty was performed in 37
      of 68 patients with 8.8% mortality (38.5% of acute and emergency cases and 1.8%
      of elective cases). The results indicated that elective unprotected LMCA
      angioplasty is relatively feasible and effective under scheduled angiographic
      follow-up.

PMID- 10073782
TI  - Plasma soluble intercellular adhesion molecule-1 levels in coronary circulation
      in patients with unstable angina.
AB  - It has been suggested that active inflammation plays an important role in the
      pathogenesis of acute coronary syndromes, including unstable angina.
      Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial
      cells for adherence of the activated polymorphonuclear leukocytes. Recently, it
      has been demonstrated that the soluble form of ICAM-1 has been detected in human
      serum and has been increased in many other inflammatory or autoimmune disorders.
      To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma
      soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1
      levels in the coronary sinus and aortic root were simultaneously examined in 20
      patients with unstable angina, 19 patients with stable exertional angina, and 16
      control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked
      immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter)
      both in the coronary sinus and aortic root were significantly higher (p <0.01) in
      patients with unstable angina than in those with stable exertional angina and in
      control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13
      vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher
      in the coronary sinus than in the aortic root in patients with unstable angina.
      There were no significant differences in the values between in the coronary sinus
      and aortic root in patients with stable exertional angina and control subjects.
      Thus, sICAM-1 release is increased, especially in coronary circulation in
      unstable angina.

PMID- 10073783
TI  - Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no
      answer yet. QUIET Investigators. QUinapril Ischemic Event Trial.
AB  - Angiotensin-converting enzyme inhibitors have proven to be of clinical benefit in
      congestive heart failure. Whether they also provide benefit to patients with
      coronary artery disease in the absence of congestive heart failure via an
      antiatherosclerotic mechanism is a question the QUinapril Ischemic Event Trial
      quantitative coronary angiography (QCA) study attempted to answer: 1,750 patients
      with normal left ventricular function who were undergoing coronary angiography
      and angioplasty were randomized to 20 mg/day of quinapril versus placebo and
      followed for 3 years for cardiac end points. A randomly selected subgroup of the
      total cohort underwent follow-up angiography. The primary QCA end point was the
      categorical designation of progression versus nonprogression, defined either by
      QCA or by a cardiac event in patients selected for the QCA trial who had no
      usable follow-up x-ray film. Secondary end points in patients with 2 angiograms
      were: new stenosis development, change in minimum lumen diameter index, and
      change in percent diameter stenosis index. There were 119 progressors among 243
      placebo-treated patients (49%) and 111 progressors among 234 quinapril-treated
      patients (47%) (p = NS). There were 44 patients with new stenosis development in
      the placebo group (19%) and 50 (22%) in the quinapril group (p = NS). Change in
      minimum lumen diameter index was -0.21+/-0.03 mm in the placebo group and -0.18+/
      0.03 mm in the quinapril group (p = NS). Finally, change in percent diameter
      stenosis index was +5.1+/-1.0 in the placebo group and +3.5+/-1.0 in the
      quinapril group (p = NS). Potential confounders of this trial are presented and
      discussed.

PMID- 10073784
TI  - Segmental myocardial contractility versus perfusion in Kawasaki disease with
      coronary arterial aneurysm.
AB  - The impact of Kawasaki-related coronary injury on the myocardium was evaluated in
      13 patients with persistent coronary aneurysm after a follow-up period of 7.92+/
      3.97 years (range 1.8 to 14.3). Myocardial segmental perfusion and contractility
      integrity were assessed by resting and exercise echocardiography and technetium
      99 (Tc-99m) sestamibi scan. Eight patients (61.5%) had giant aneurysms (> or = 8
      mm) and 9 had multivessel involvement; the mean diameter of the largest aneurysm
      was 8.6+/-2.5 mm (range 5 to 14). During the acute phase, myocardial infarction
      occurred in 1 patient and coronary thrombosis in another. At the latest
      echocardiographic evaluation, the mean aneurysm diameter was 6.8+/-2.4 mm (range
      4.5 to 12), there was persistent giant aneurysms in 5 of 8 patients, and 3 of 9
      patients had multivessel involvement. Coronary angiography demonstrated stenosis
      in 7 of 10 patients, with multiple levels in 2. At sestamibi scan, all 13
      patients had perfusion anomalies at rest, whereas only 7 had detectable
      hypokinesia on echocardiography. With exercise, perfusion returned to near normal
      in 3 patients, improved in 3, remained unchanged in 4, and worsened in 3
      patients. Segmental contractility similarly deteriorated in the latter 3 patients
      but also in 2 patients whose perfusion scan had improved with exercise. Three
      patients, normal at rest, developed segmental hypokinesia during exercise. When
      present, the location of observed changes in contractility on stress
      echocardiography corresponded to that of perfusion defect. In conclusion,
      abnormal myocardial perfusion is present long term after complicated Kawasaki
      disease, the worst anomalies accompanying persistent giant aneurysms. Unfavorable
      perfusion response was coupled with abnormal contractility; however, enhanced
      perfusion with exercise correlated poorly with segmental contractility response.

PMID- 10073785
TI  - Type of alcoholic beverage and risk of myocardial infarction.
AB  - We examined the relation of alcoholic beverage type and risk of myocardial
      infarction (MI) in a case-control study among 340 cases of MI and an equal number
      of age-, sex-, and community-matched controls. Alcohol consumption was estimated
      using a food frequency questionnaire, with alcohol drinkers defined as those
      consuming > or = 1/2 drink/day on average of any alcoholic beverage. Beer, wine,
      and liquor drinkers had at least half of their consumption from 1 beverage type.
      Fasting venous blood samples were obtained and analyzed for lipid profiles.
      Compared with nondrinkers, after adjustment for age and sex, reductions in risk
      of MI were similar for regular drinkers of any type of alcoholic beverage
      (relative risk [RR] 0.54; 95% confidence interval [CI] 0.37 to 0.79; p = 0.001),
      beer (RR 0.55; 95% CI 0.31 to 0.97; p <0.05), wine (RR 0.48; 95% CI 0.27 to 0.87;
      p <0.05), and liquor (RR 0.59; 95% CI 0.38 to 0.91; p <0.05) drinkers. Comparable
      benefits remained apparent even after multivariate adjustment for a wide range of
      nonlipid coronary risk factors. High-density lipoprotein (HDL) levels were
      significantly higher in all 4 beverage categories when compared with levels in
      nondrinkers, and as expected, adjustment for total HDL, a major direct effect of
      alcohol, substantially attenuated the protective effect in all 4 beverage
      categories. Relative risks were 0.94 for any beverage, 1.09 for beer, 0.97 for
      wine, and 0.83 for liquor after further adjustment. This strongly suggests that
      the protective effect of each beverage type is, in large part, mediated by
      increased HDL. These data indicate that regular consumption of small to moderate
      amounts of alcoholic beverages, regardless of the type, reduces the risk of MI,
      and further suggest that there is benefit, in large part, from increases in HDL
      levels.

PMID- 10073786
TI  - Efficacy of amiodarone for the termination of persistent atrial fibrillation.
AB  - The efficacy and safety of amiodarone in the conversion of persistent atrial
      fibrillation (AF) were investigated in a prospective, randomized, controlled
      study. Of 67 consecutive patients (32 men, mean age 64+/-9 years) with AF lasting
      >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical
      characteristics were similar in the 2 groups. Patients randomized to amiodarone
      received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They
      were also given 600 mg/day orally, divided into 3 doses, for 1 week and
      thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an
      identical amount of saline IV over 24 hours and then oral placebo for 1 month.
      Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who
      received amiodarone and in none of the 34 patients in the placebo group (p
      <0.001). None of the patients converted to sinus rhythm within the first 3 days.
      Those who converted had smaller atria than those who did not (diameter 41.9+/-7.2
      vs 50.4+/-5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular
      ejection fraction, and the duration of AF did not differ significantly between
      patients who converted and those who did not. No side effects requiring
      discontinuation of treatment were observed in either group. Amiodarone,
      administered both intravenously and orally, appears to be safe and effective in
      the termination of persistent AF. Left atrial diameter is the sole independent
      predictor of conversion.

PMID- 10073787
TI  - Lung membrane diffusing capacity, heart failure, and heart transplantation.
AB  - The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic
      heart failure and remains decreased after heart transplantation. This decrease in
      DLCO may depend on a permanent alteration after transplantation of one or the
      other of its components: diffusion of the alveolar capillary membrane or the
      pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane
      conductance, and Vc before and after heart transplantation. At the time of
      hemodynamic measurements, the Roughton and Forster method of measuring DLCO at
      varying alveolar oxygen concentrations was used to determine the membrane
      conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and
      thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume)
      in 21 patients with class III to IV heart failure before and after
      transplantation, and in 21 healthy controls. Transplantation normalized pulmonary
      capillary pressure and increased cardiac index. DLCO was decreased before
      transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal
      (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained
      unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18
      ml before and after transplantation) and thetaVc/VA was not compensated by the
      changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after
      transplantation, respectively) and membrane conductance/VA. We conclude that the
      decrease in DLCO in patients with chronic heart failure is due to a restrictive
      ventilatory pattern because their DLCO/VA remains normal; the decrease in the
      membrane conductance is compensated by the increase in Vc. After transplantation,
      the decrease in Vc due to normalization of pulmonary hemodynamics is not
      completely compensated for by an increase in membrane conductance. Because the
      membrane conductances, measured before and after transplantation, are negatively
      correlated with duration of heart failure, its abnormal pulmonary hemodynamics
      may have irreversibly altered the alveolar capillary membrane.

PMID- 10073788
TI  - Jeffrey Michael Isner, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 10073789
TI  - Consultation before thrombolytic therapy in acute myocardial infarction. Second
      National Registry of Myocardial Infarction (NRMI 2) Investigators.
AB  - Among 57,398 thrombolytic recipients in the National Registry of Myocardial
      Infarction 2, consultation with another physician was sought in 64% before
      initiating lytic therapy, although presenting features were typical, rather than
      atypical, in most patients. Consultation significantly delayed the administration
      of lytic therapy and was associated with increased hospital mortality.

PMID- 10073790
TI  - Detecting and differentiating white from red coronary thrombus by angiography in
      angina pectoris and in acute myocardial infarction.
AB  - To determine the ability to detect thrombus by angiography, angioscopy was
      performed before angiography in patients undergoing interventional procedures and
      the data collected in a blinded fashion. These data demonstrated that the
      sensitivity of angiography to detect white thrombus was 50% and the specificity
      was 95%, whereas the sensitivity and specificity to detect red thrombus was 100%,
      respectively; the positive and negative predictive value of detecting thrombus in
      general was 89% and 83%, respectively.

PMID- 10073791
TI  - Effect of niacin and etofibrate association on subjects with coronary artery
      disease and serum high-density lipoprotein cholesterol <35 mg/dl.
AB  - Niacin treatment (alone) was compared with etofibrate and niacin combination to
      treat patients with high-density lipoprotein <35 mg/dl and without
      hypertriglyceridemia. The niacin and etofibrate combination proved to be safe and
      increased high-density lipoprotein cholesterol levels to 48%, which was 3 times
      higher than that obtained with niacin alone.

PMID- 10073792
TI  - Prognostic value of negative dobutamine stress echo in women with intermediate
      probability of coronary artery disease.
AB  - Women with an intermediate pretest probability of coronary artery disease
      represent a significant proportion of patients referred for the investigation of
      chest pain. Dobutamine stress echocardiography can be used to restratify these
      patients into a low-risk group without resorting to cardiac catheterization.

PMID- 10073793
TI  - Detection of exercise-induced reversible right ventricular wall motion
      abnormalities using echocardiographic determined tricuspid annular motion.
AB  - Effects of exercise on tricuspid annular motion at the right ventricular free
      wall was studied by echocardiography. The results suggest that exercise-related
      reversible changes in tricuspid annular motion may be used to identify patients
      with proximal right coronary artery stenosis.

PMID- 10073794
TI  - Comparison of perception of angina pectoris during exercise testing in African
      Americans versus Caucasians.
AB  - In a sample of 142 patients with positive treadmill test results, we found that
      African-Americans reported anginal pain during exercise at nearly twice the rate
      of Caucasians, and had a significantly shorter time to angina. The mechanisms for
      these race differences remain to be elucidated, but may include underlying
      physiologic responses, ethnocultural differences, psychological state,
      socioeconomic differences, and experimenter bias.

PMID- 10073795
TI  - Plasma platelet-activating factor acetylhydrolase activity is not associated with
      premature coronary atherosclerosis.
AB  - Platelet-activating factor acetylhydrolase activity in plasma was compared
      between 72 subjects with angiographically normal coronary arteries and matched
      controls with clinically significant obstruction. No difference was seen, and we
      conclude that variation in plasma platelet-activating factor acetylhydrolase
      activity is not a risk factor for coronary artery disease.

PMID- 10073796
TI  - Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram
      in patients with paroxysmal atrial fibrillation and coronary artery disease.
AB  - The effects of a 6-week treatment with amiodarone on the P-wave triggered signal
      averaged electrocardiogram in patients with paroxysmal atrial fibrillation and
      coronary artery disease have been studied. Amiodarone favorably influences P-wave
      triggered signal-averaged electrocardiographic parameters, predominantly in
      patients in whom amiodarone is effective in preventing paroxysmal atrial
      fibrillation.

PMID- 10073797
TI  - Efficacy of bretylium tosylate for ventricular tachycardia.
AB  - In 20 patients with inducible ventricular tachycardia (VT), intravenous bretylium
      tosylate infused as a 10-mg/kg bolus followed by 2 mg/min caused no change in
      refractory periods and did not suppress inducibility of VT. The use of bretylium
      for the treatment of VT should be reexamined.

PMID- 10073798
TI  - The dimensions of the triangle of Koch in children.
AB  - We measured the dimensions of Koch's triangle in children with normal
      intracardiac anatomy to determine the relation between the size of the triangle
      of Koch and patient age, weight, height, and body surface area. We found that the
      dimensions of Koch's triangle varies significantly and directly with patient age
      and body habitus in this pediatric population.

PMID- 10073799
TI  - Left ventricular versus biventricular dysfunction in idiopathic dilated
      cardiomyopathy.
AB  - Eighty-five consecutive patients with idiopathic dilated cardiomyopathy were
      categorized according to the presence (biventricular dysfunction) or absence
      (left ventricular [LV] dysfunction) of reduced right ventricular ejection
      fraction (<35%) along with reduced LV ejection fraction (<50%). Compared with the
      36 patients with LV dysfunction, the 49 patients with biventricular dysfunction
      had significantly worse New York Heart Association functional class (2.7+/-0.6 vs
      1.9+/-0.5; p <0.001), LV ejection fraction (26+/-10% vs 34+/-8%; p <0.0001), and
      outcome (transplant-free survival, 55% vs 89%; p <0.001). Thus, dilated
      cardiomyopathy is frequently characterized by biventricular involvement, which
      identifies a more severe disease and a worse long-term prognosis.

PMID- 10073800
TI  - Effect of oxymetholone on left ventricular dimensions in heart failure secondary
      to idiopathic dilated cardiomyopathy or to mitral or aortic regurgitation.
AB  - This study suggests that the short-term administration of a small dosage of
      anabolic steroids may have a beneficial effect on the deteriorated myocardium,
      although long-standing exposure to a larger dosage of anabolic steroids may
      induce myocardial and systemic complications.

PMID- 10073801
TI  - Predictors and significance of atrial rhythm before and six months after
      percutaneous balloon mitral commissurotomy.
AB  - Clinical, echocardiographic, and cardiac catheterization data were evaluated in
      263 patients with mitral stenosis who were undergoing balloon commissurotomy to
      determine the predictors of atrial rhythm and its effect on functional status.
      Conversion from atrial fibrillation to sinus rhythm at 6 months after the
      procedure occurred in 16 of 86 patients (19%) and was predicted by the duration
      of atrial fibrillation, baseline functional class, and antiarrhythmic therapy;
      patients who remained in atrial fibrillation had a poorer functional status
      compared with those in sinus rhythm despite similar procedural results.

PMID- 10073802
TI  - Heart rate variability in carcinoid heart disease.
AB  - Time domain heart rate variability measurements and echocardiographic studies
      were performed in 35 patients with carcinoid syndrome. Carcinoid heart disease
      was present in 18 patients (51%). Heart rate variability parameters (standard
      deviation of all normal RR intervals, percentage of the number of pairs of
      adjacent normal RR intervals differing by >50 ms) were significantly reduced in
      patients with than in those without carcinoid heart disease.

PMID- 10073803
TI  - Frequency of echocardiographic improvement in left ventricular cavity size and
      contractility in idiopathic-dilated cardiomyopathy.
AB  - In this study, we used 2-dimensional echocardiography to serially evaluate 32
      patients with recent onset dilated cardiomyopathy. We found that in 12 patients
      (37%) there was resolution of left ventricular dilation as well as concomitant
      normalization of left ventricular contractility.

PMID- 10073804
TI  - Transesophageal echocardiographic Doppler findings in patients with penetrating
      aortic ulcers.
AB  - Penetrating aortic ulcers and intramural hematomas cannot always be
      differentiated by transesophageal echocardiography. We suggest that color and
      pulsed-wave Doppler flow can be used for identifying penetrating aortic ulcers.

PMID- 10073805
TI  - Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary
      arteries.
AB  - Intravascular ultrasound demonstrated plaque ruptures that occurred in regions
      involved with large complicated atherosclerotic plaques in the coronary artery.
      Because intravascular ultrasound evaluates both plaque and luminal dimensions, it
      contributes to our understanding of the pathophysiology of coronary artery
      disease.

PMID- 10073806
TI  - Fatal neutropenia and thrombocytopenia associated with ticlopidine after
      stenting.
AB  - We report 3 cases of fatal neutropenia and thrombocytopenia associated with
      ticlopidine after coronary stenting. Patients should be counseled about the early
      signs of infection and bleeding and to have regularly scheduled complete blood
      counts.

PMID- 10073807
TI  - Does length of training account for differences in practice patterns among
      Canadian and American cardiologists?

PMID- 10073808
TI  - Patients undergoing cardioversion of atrial flutter should be routinely
      anticoagulated.

PMID- 10073809
TI  - Comparing echocardiographic with radionuclide assessment of left ventricular
      ejection fraction.

PMID- 10073810
TI  - John, not James Hunter.

PMID- 10073811
TI  - Correlation of angiographic findings and right (V1 to V3) versus left (V4 to V6)
      precordial ST-segment depression in inferior wall acute myocardial infarction.
AB  - This study assessed whether differences in the underlying mechanisms for various
      patterns of precordial ST-segment depression with inferior acute myocardial
      infarction (AMI) are associated with poorer prognoses. We studied 1,155 patients
      with inferior AMI who underwent thrombolysis in the Global Utilization of
      Streptokinase and TPA for Occluded arteries (GUSTO-I) angiographic substudy:
      those without precordial ST depression (n = 412; 35.7%), those with maximum ST
      depression in leads V1 to V3 (n = 547; 47.4%), and those with maximum ST
      depression in leads V4 to V6 (n = 196; 17.0%) on admission electrocardiogram. We
      compared the infarct-related artery, presence of left anterior descending or
      multivessel coronary artery disease, and left ventricular function among groups.
      Patients with maximum ST depression in leads V4 to V6 more often had 3-vessel
      disease (26.0%) than those without precordial ST depression (13.5%) or those with
      ST depression in leads V1 to V3 (15.7%; p = 0.002), and they had a lower ejection
      fraction (median 54% vs 60% and 55%, respectively; p <0.001). Patients with
      maximum ST depression in leads V1 to V3 less often had AMIs due to proximal right
      coronary artery obstruction (23.9%) than patients without precordial ST
      depression (35.2%) or those with ST depression in leads V4 to V6 (40.0%; p =
      0.001) and had larger AMIs as estimated by peak creatine kinase. Different
      patterns of precordial ST depression are associated with distinctive coronary
      anatomy. ST depression in leads V4 to V6, but not V1 to V3, confers a greater
      likelihood of multivessel coronary artery disease.

PMID- 10073812
TI  - Reduced vasodilator capacity in syndrome X related to structure and function of
      resistance arteries.
AB  - The combination of angina pectoris, angiographically normal epicardial coronary
      arteries, and a positive exercise test is referred to as syndrome X. Previous
      studies have demonstrated an impaired coronary flow reserve and a peripheral
      vascular dysfunction, suggesting that vascular abnormalities in syndrome X may
      not be confined to the heart. The aim of this study was to investigate whether
      any vascular disorder of syndrome X is due to intrinsic structural or functional
      disturbances in resistance arteries. We compared 16 patients with syndrome X
      (56.6+/-1.2 years, 3 men) with 15 matched control subjects. Myocardial blood flow
      was measured with 13N-ammonia positron emission tomography. Forearm blood flow
      was measured in the brachial artery with high-resolution ultrasound. Gluteal
      subcutaneous resistance arteries were dissected and mounted on a myograph for
      measurement of active tension development, lumen diameter, and media thickness.
      Baseline myocardial blood flow was similar in patients and controls, but
      dipyridamole-induced hyperemia was decreased in patients (1.67+/-0.13 vs 2.31+/
      0.12 ml/ min/g, p <0.01). Patients and controls had similar baseline forearm
      blood flow, but hyperemic flow after transient occlusion of the brachial artery
      was impaired in patients (198+/-20 vs 273+/-32 ml/min, p <0.05). Isolated
      resistance arteries showed no differences in constriction to noradrenaline, or
      relaxation to acetylcholine, dipyridamole, or nitroglycerin. Furthermore, the
      ratio between media thickness and lumen diameter were similar in syndrome X
      patients and controls. Our data show that when compared with a well-matched
      control group, syndrome X patients have a decreased coronary and peripheral
      vasodilator capacity. However, this is not reflected by functional abnormalities
      or structural changes as evaluated in subcutaneous resistance arteries. We
      conclude that syndrome X is not a generalized intrinsic abnormality of the
      resistance circulation.

PMID- 10073813
TI  - Early diagnosis of acute myocardial infarction in patients without ST-segment
      elevation.
AB  - Early identification of acute myocardial infarction (AMI) is necessary to
      initiate appropriate treatment. In patients presenting without ST-segment
      elevation, diagnosis is often dependent on the presence of elevated myocardial
      markers. This study examines the ability of serial MB mass alone and in
      combination with myoglobin in diagnosing AMI in patients without ST-segment
      elevation within 3 hours of presentation. In all, 2,093 patients were admitted
      and underwent serial marker analysis using myoglobin, creatine kinase (CK), and
      CK-MB at 0, 3, 6, and 8 hours. AMI was diagnosed by a CK-MB > or =8.0 ng/ml and a
      relative index (RI) (CK-MB x 100/total CK) > or =4.0. A total of 186 patients
      (9%) were diagnosed with AMI. The optimal diagnostic strategy was an elevated CK
      MB + RI on the initial or 3-hour sample or at least a twofold increase in CK-MB
      without exceeding the upper range of normal over the 3-hour time period
      (sensitivity 93%, specificity 98%). The combination of an elevated CK-MB + RI or
      myoglobin on the initial or 3-hour sample had a sensitivity of 94%, although
      specificity was significantly lower, at 86%. Sensitivities and specificities
      after exclusion of the 242 patients with ischemic electrocardiographic changes
      were essentially unchanged. We conclude that most patients with AMI presenting
      with nondiagnostic electrocardiograms can be diagnosed within 3 hours of
      presentation.

PMID- 10073814
TI  - Antecedent angina pectoris as a predictor of better functional and clinical
      outcomes in patients with an inferior wall acute myocardial infarction.
AB  - We examined whether angina pectoris (AP) occurring shortly before the onset of
      acute myocardial infarction (AMI) can render the right ventricle and the
      conducting tissue resistant to ischemia in 75 patients with an inferior wall AMI.
      Each patient had total occlusion in the proximal right coronary artery and
      underwent successful coronary angioplasty < or =24 hours from the onset. We
      divided patients into 2 groups based on presence or absence of antecedent AP < or
      =24 hours before the system onset: group 1 (absent) = 57 patients; group 2
      (present) = 18 patients. Collateral circulation was more frequently observed in
      group 2 than in group 1 (group 1 vs 2, 28% vs 61%, p <0.01). Elevation in ST
      segment > or =1 mm in lead V4R, hemodynamic right ventricular dysfunction, and
      frequency of high-degree heart block were more frequent in group 1 than in group
      2 (75% vs 44%, 79% vs 39%, 53% vs 11%, p <0.05, respectively). Multivariate
      analysis demonstrated that antecedent AP is the only factor related to these
      complications. Thus, episodes of AP occurring shortly before onset may restrain
      development of ischemic damage of the right ventricle and conducting tissue, and
      are associated with better clinical and functional outcomes among patients with
      an inferior wall AMI.

PMID- 10073815
TI  - Usefulness of the presenting electrocardiogram in predicting successful
      reperfusion with streptokinase in acute myocardial infarction.
AB  - The presenting electrocardiogram may contain information indicating the
      probability of successful reperfusion. The relation between 3 parameters in the
      presenting electrocardiogram (pathologic Q waves, T-wave inversion, and the slope
      of ST elevation) and Thrombolysis in Myocardial Infarction trial (TIMI) grade 3
      flow in the infarct-related artery was assessed angiographically 90 minutes after
      beginning streptokinase in 362 patients. TIMI grade 3 flow was more common in
      patients without Q waves (55%) than in those with Q waves (35%; p <0.001), and
      more common in patients without T-wave inversion (50%) than in those with T-wave
      inversion (30%; p <0.002). There was no relation between the slope of the ST
      segment or the magnitude of its deviation and the achievement of TIMI grade 3
      flow. Only 20% of the 59 patients with both Q waves and T-wave inversion had TIMI
      grade 3 flow, compared with 50% of the remaining patients (p <0.0001). Among
      patients treated within 3 hours, TIMI grade 3 flow was seen in 68% of those
      without versus 44% of those with Q waves (p <0.01), and in 62% of those without
      versus 43% of those with T-wave inversion (p = 0.06). Among patients treated
      after 3 hours, TIMI grade 3 flow was seen in 38% of those without versus 30% of
      those with Q waves (p = NS), and in 38% of those without versus 23% of those with
      T-wave inversion (p <0.05). On multivariate analysis, the absence of Q waves, the
      time from the onset of chest pain to treatment, and age were independent
      predictors of TIMI grade 3 flow. Pathologic Q waves in the presenting
      electrocardiogram provide valuable information as to the probability of achieving
      successful reperfusion following administration of streptokinase, and may be
      helpful for triage of patients to alternative reperfusion strategies, including
      percutaneous revascularization.

PMID- 10073816
TI  - Preoperative assessment of cardiac risk in noncardiac major vascular surgery.
AB  - We evaluated whether a preoperative clinical algorithm allows an adequate
      stratification in cardiac risk and the predictive value of dipyridamole thallium
      201 scintigraphy and rest echocardiography for postoperative adverse cardiac
      outcomes. Three hundred twenty patients undergoing 338 vascular surgery
      procedures were prospectively stratified into low, intermediate, and high risk.
      The low- and intermediate-risk patients underwent surgery without further
      diagnostic evaluation. In 7 high-risk patients the vascular procedure was
      canceled (1 died of myocardial infarction at 6-month follow-up), 9 underwent
      presurgical myocardial revascularization (1 died of myocardial infarction), and
      49 underwent vascular surgery with perioperative intensive care treatment.
      Hospital mortality was 3.8%. Cardiac mortality and morbidity were 1.5% and 10.4%,
      respectively. We observed a significant difference in "hard" (death, myocardial
      infarction, pulmonary edema, major arrhythmias) and "soft" (myocardial ischemia,
      minor arrhythmias) events between groups, p <0.001. Previous pulmonary edema was
      a predictive variable of cardiac outcomes (multiple logistic regression
      analysis). Ninety-nine of 220 intermediate-risk patients randomly underwent
      dipyridamole thallium-201 scintigraphy: 37 had redistribution, 10 persistent, and
      52 no defects; 7 of 13 soft and hard cardiac events occurred in patients without
      redistribution defects. Sensitivity, specificity, and positive and negative
      predictive values of redistribution defects for postoperative adverse outcomes
      were 38%, 63%, 14%, 87%, respectively. This algorithm may provide a safe and cost
      effective approach (average cost saving per patient $1,500) to cardiac risk
      stratification. These results suggest that routine use of dipyridamole thallium
      201 scintigraphy for screening of intermediate-risk patients may not be
      warranted.

PMID- 10073817
TI  - Intravascular ultrasound predictors of target lesion revascularization after
      stenting of protected left main coronary artery stenoses.
AB  - We evaluated the predictors of late clinical outcomes after stenting of protected
      left main coronary artery (LMCA) stenoses. Intravascular ultrasound (IVUS) guided
      stenting of protected LMCA stenoses was performed in 87 consecutive patients
      between January 1994 and December 1996. Results were evaluated using conventional
      (clinical, angiographic, and IVUS) methodology. Late (12 month) clinical follow
      up information was obtained in all patients. Initial procedural success was
      achieved in 86 patients (99%). There was 1 in-hospital death (in the 1 patient
      with a procedural failure). There were no other in-hospital complications,
      including Q-wave myocardial infarction, emergency bypass surgery, or repeat
      coronary angioplasty. The overall target lesion revascularization (TLR) rate was
      13%. Using multivariate logistic regression analysis, the only independent
      predictor of TLR was the postintervention lumen area by IVUS. A final lumen area
      > or =7.0 mm2 was obtained in 74 patients (86%); the TLR rate for these patients
      was 7%. This was compared with patients with a final lumen area <7.0 mm2 in whom
      the TLR rate was 50% (p = 0.0011). Stenting of protected LMCA stenoses is safe
      and effective with acceptable long-term clinical outcomes. The most important
      factor determining long-term success was the postintervention lumen area by IVUS.

PMID- 10073818
TI  - Ultrasonic assessment of vascular complications in coronary angiography and
      angioplasty after transradial approach.
AB  - The transradial approach has currently been accepted as an alternative entry
      method for coronary angiography and angioplasty. Vascular complications of this
      method were evaluated by 2-dimensional echo and color Doppler ultrasonic studies
      in 162 patients before, early (2+/-2 [mean+/-SD] days), and late (95+/-29 days)
      after catheterization. Mean age was 64+/-10 years, and 103 were men. Coronary
      angioplasty was performed in 59 patients (79 lesions) with angiographic success
      in 92%. Early after the procedure, segmental stenosis was noted in 35 patients
      (22%) and no flow in 15 patients (9%). Late after the procedure, segmental
      stenosis was noted in 2, diffuse stenosis in 36 (22%), and no flow in 8 (5%)
      patients. The cessation of radial artery pulse was unpalpable in only 2% of
      cases, whereas radial flow by color Doppler was undetectable in 9% early after
      the procedure. Late after the procedure, recanalization was observed in 60% of
      these occluded cases. Thirty-three of 86 patients (38%) with no flow or diffuse
      stenosis had radial artery diameters smaller than the sheath diameter, and 11 of
      76 patients (14%) had radial artery diameters larger than the sheath diameter (p
      <0.01). Multivariate analysis revealed risk factors for vascular complications:
      (1) Radial artery diameter before the procedure was one of the significant and
      independent determinants of no flow both early (p = 0.06) and late (p = 0.004)
      after the procedure. (2) The difference in radial artery diameter and sheath size
      was related to the occurrence of diffuse stenosis late after the procedure (p =
      0.003). (3) Diabetes mellitus was related to no flow (p = 0.05) or diffuse
      stenosis (p = 0.11) late after the procedure. Thus, ultrasonic evaluation of the
      radial artery was useful in selecting both an access route and an appropriate
      size of the sheath to determine early and late vascular complications.

PMID- 10073819
TI  - Electrophysiology and endocardial mapping of induced atrial fibrillation in
      patients with spontaneous atrial fibrillation.
AB  - We analyzed the patterns of atrial activation and characterized the
      electrophysiologic properties of regional atrial sites in the, right atrium and
      left atrium at the onset of atrial fibrillation (AF) induced with programmed
      right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return
      cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps
      during AF, and the stability and reproducibility of atrial activation sequences
      at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of
      intracardiac electrograms with surface electrocardiographic morphology was
      attempted. Maximum intraatrial conduction delay for high RA premature beats was
      observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or
      interatrial septum (n = 15). The return cycle lengths for the first AF cycle
      showed increasing conduction delay with increasing prematurity of the last
      extrastimulus in most patients. Suprisingly, discrete atrial electrograms with
      regular or irregular cycle lengths were present at the onset of
      electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented
      or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF
      but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p =
      0.001). The atrial activation sequence at the onset of the induced AF elicited by
      high RA extrastimuli usually showed the earliest activation site at the crista
      terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced
      AF elicited from other RA sites usually showed earliest atrial activation at the
      septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation
      sequences for the first induced AF cycle were usually reproducible in most
      patients. Atrial activation patterns during the first 10 cycles for AF were
      stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated
      significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We
      conclude that pacing induced AF elicited by RA premature beats commences as a
      regular or irregular rapid atrial tachycardia consistent with a transitional, but
      often organized, arrhythmia. The activation sequence and electrophysiologic
      behavior of the first induced AF cycle is consistent with intraatrial reentry and
      reproducible in most patients. More than 1 atrial activation sequence can
      sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant
      circuits.

PMID- 10073820
TI  - Plasma adenosine levels and platelet activation in patients with atrial
      fibrillation.
AB  - Platelet activation is observed in patients with atrial fibrillation (AF). P
      selectin, which is expressed on platelet activation, plays an important role in
      the formation of thromboemobli. Because adenosine is known to attenuate platelet
      activation, we evaluated adenosine levels and 2 indicators of platelet
      activation, i.e., expression of P-selectin on platelets and plasma levels of beta
      thromboglobulin, in 28 patients with AF (20 men and 8 women, age range 64+/-2
      years) with sex- and age-matched (+/-2 years) subjects with sinus rhythm. The
      incidence of risk factors for stroke except for coronary heart disease and in
      echocardiographic parameters did not differ between the 2 groups. Plasma
      adenosine levels were lower (p <0.05) in patients with AF than in controls (mean
      [interquartile range] 13.4 [19.3-9.3] vs 19.1 [30.8-11.9] nmol/L). The expression
      of P-selectin on platelets (6.8% [13.6-3.4] vs 4.0% [8.8-1.8]) and plasma levels
      of beta-thromboglobulin were higher (p <0.05) in patients with AF. Flow
      cytometric analysis revealed that an antagonist of adenosine receptors, 8
      sulfophenyltheophylline, increased the expression of P-selectin on platelets in a
      dose-dependent manner in the in vitro study. These results suggest that decreased
      plasma levels of adenosine were associated with platelet activation in patients
      with AF. Substitution of adenosine may provide a strategy for preventing platelet
      activation in these patients.

PMID- 10073821
TI  - Usefulness of transthoracic echocardiography in detecting significant prosthetic
      mitral valve regurgitation.
AB  - To identify the transthoracic echo-Doppler (TTE) variables most predictive of
      significant mitral regurgitation (MR) of mechanical prosthetic valves, TTE and
      trans-esophageal echo (TEE) studies were independently reviewed in 57 patients
      (mean age [+/-SD] 59+/-12.5 years) undergoing both studies within 2+/-3 days.
      Several 2-dimensional and Doppler hemodynamic variables from the TTE studies were
      derived. Prosthetic MR was significant (moderate or severe) by TEE in 20
      patients, whereas mild or no MR was seen in 37 patients. The best univariate
      predictors of significant MR by TTE were peak velocity of mitral inflow, mean
      gradient, tricuspid regurgitation velocity, isovolumic relaxation time, and ratio
      of time velocity integral of mitral inflow to time velocity integral in the left
      ventricular outflow (TVI(MV)/TVI(LVO)). Peak mitral velocity and TVI(MV)/TVI(LVO)
      were the best predictors of significant MR and performed similarly (area under
      the receiver-operating characteristic curve: 0.97 for both). A peak velocity of >
      or =1.9 m/s was 90% sensitive and 89% specific for significant prosthetic MR,
      whereas a TVI(MV)/TVI(LVO) > or =2.5 had a sensitivity and specificity of 89% and
      91%, respectively. A decision tree was constructed to assess the conditional
      probabilities of having significant MR given all the possible outcomes of the 2
      best predictors. None of the patients with peak velocity < 1.9 m/s and
      TVI(MV)/TVI(LVO) <2.5 by TTE had significant MR. Conversely, all patients with
      peak velocity > or =1.9 m/s and TVI(MV)/TVI(LVO) > or =2.5 had significant MR.
      The use of more complex algorithms did not further improve the results. Thus,
      measurements of hemodynamic Doppler variables on TTE examination can accurately
      identify a large number of patients without significant prosthetic MR, thereby
      reducing the need for further investigation with TEE.

PMID- 10073822
TI  - Analysis of ventricular septal motion by doppler tissue imaging in atrial septal
      defect and normal heart.
AB  - The aortic root and the upper part of the ventricular septum moves anteriorly in
      early systole, while the lower part moves posteriorly. The hinge of the
      counterpart motion of the ventricular septum is called pivot point. Using Doppler
      tissue imaging (DTI), we attempted to clarify the location of the pivot point of
      the ventricular septum in children with normal heart and with atrial septal
      defect (ASD), and to investigate the relation between the degree of the downward
      shift of the pivot point and that of volume overload of the right ventricle in
      patients with ASD. Study subjects consisted of 20 healthy children and 36
      patients with ASD, aged from 1 to 15 years (mean 5.7+/-3.4) in the normal group
      and 6 months to 12 years (mean 4.4+/-3.2) in the ASD group, respectively. The
      pivot point was designated as a border of the color signal of DTI of the
      ventricular septum in early systole. Measurements were then obtained on cross
      sectional echocardiography and DTI: septal length in the parasternal long-axis
      view, distance from aortic valve to pivot point in early systole, diastolic left
      ventricular internal dimension, and diastolic right ventricular internal
      dimension. In the normal group, the ratio of distance from aortic valve to pivot
      point/septal length was 0.13+/-0.049, whereas it was 0.26+/-0.168 in the group
      with ASD (p <0.001). In the ASD group, the distance from aortic valve to pivot
      point normalized by body surface area (mm/m2) correlated with the ratio of
      diastolic right/left ventricular internal dimension and with the ratio of
      pulmonary to systemic flow (Qp/Qs) (r = 0.63 and 0.50, respectively). The ratio
      of the distance from aortic valve to pivot point/septal length correlated with
      the ratio of diastolic right/left ventricular internal dimension and Qp/Qs (r =
      0.56 and 0.44, respectively). By DTI, the pivot point was located at the upper
      13+/-5% of the total length of the ventricular septum in normal children, and was
      located at 26+/-17% in patients with ASD (p < 0.001). The degree of this
      displacement in ASD correlated with that of volume overload of the right
      ventricle. The paradoxic motion of the ventricular septum shown in the ASD could
      be explained by this downward shift of the pivot point.

PMID- 10073823
TI  - Comparison of native and contrast-enhanced harmonic echocardiography for
      visualization of left ventricular endocardial border.
AB  - Our study was designed to compare the utility of fundamental and second harmonic
      imaging (SH) for visualization of the left ventricular (LV) endocardial border.
      SH is a new imaging modality using nonlinear acoustic response, which may provide
      better endocardial border delineation. Standard apical views were studied in 42
      patients using fundamental frequency (FF), SH without contrast (1.6- to 1.8-MHz
      and 2.1- to 2.5-MHz transmission frequencies), and SH after an intravenous
      injection of 2.5 g of Levovist. The quality of endocardial delineation in 16
      standard segments was scored from 0 to 2. The endocardial visualization index was
      calculated as a mean of the scores. SH with and without contrast significantly
      improved LV endocardial border detection (endocardial visualization index 1.25+/
      0.53, 1.64+/-0.67, 1.55+/-0.69, and 1.73+/-0.28 for fundamental, lower, and
      higher frequency harmonic and contrast-harmonic mode, respectively, p <0.005).
      Improvement was found in all LV segments. The number of invisible segments
      decreased from 142 (FF) to 54, 112, and 61 (in lower, higher, and contrast SH
      mode, respectively, p <0.001). Endocardial delineation in the apical segments
      using SH was optimal after contrast injection. In the basal LV area, contrast
      enhanced images were less informative because of signal attenuation. Thus, SH
      significantly improves visualization of the LV endocardial border. Contrast
      enhancement with Levovist improves imaging of the apical segments but has no
      additional advantage in the basal segments. SH emerges as first-line modality for
      studies of LV function.

PMID- 10073824
TI  - Comparison of tissue harmonic imaging with contrast (sonicated albumin
      echocardiography and Doppler myocardial imaging for enhancing endocardial border
      resolution.
AB  - Endocardial resolution during 2-dimensional echocardiography is technically
      limited in at least 10% to 15% of patients. Recently, several ultrasound imaging
      innovations have been introduced that may improve endocardial resolution and
      decrease the proportion of technically difficult studies. This study compares
      tissue harmonic imaging, intravenous sonicated albumin, and Doppler myocardial
      imaging in patients with technically difficult echocardiograms. Twenty-eight
      patients with known or suspected cardiac disease and poor baseline endocardial
      resolution were studied. Only harmonic imaging (conventional and optimized for
      tissue) was superior to baseline fundamental imaging (p <0.001). Harmonic imaging
      was superior to baseline imaging in all myocardial regions and in the majority of
      patients, including those with the worst baseline studies.

PMID- 10073825
TI  - Scott Montgomery Grundy, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 10073826
TI  - Immediate and long-term results of elective and emergent percutaneous
      interventions on protected and unprotected severely narrowed left main coronary
      arteries.
AB  - Percutaneous revascularization of protected and unprotected left main coronary
      arteries is associated with acceptable immediate results, but there are
      significant long-term consequences, including the need for repeat percutaneous
      intervention (10%), myocardial infarction (7.5%), coronary artery bypass surgery
      (7%), and death (38%), despite the elective or emergent nature of the procedure.

PMID- 10073827
TI  - Effects of withdrawal of chronic estrogen therapy on brachial artery
      vasoreactivity in women with coronary artery disease.
AB  - Withdrawal of oral estrogen therapy is associated with a deterioration in
      endothelial function in postmenopausal women with coronary artery disease. Our
      data also suggest that withdrawal of estrogen results in enhanced hyperemic flow,
      although this observation will require validation with further study.

PMID- 10073828
TI  - Effect of low altitude (Dead Sea location) on exercise performance and wall
      motion in patients with coronary artery disease.
AB  - To evaluate the effects of low altitude on exercise performance and myocardial
      ischemia, 12 patients with coronary artery disease and 6 normal controls
      underwent ergometric and exercise echocardiography in Haifa, 130 m above sea
      level, and at the Dead Sea, 402 m below sea level. At the Dead Sea, exercise
      duration increased by 15% (p <0.05) in the patient and control groups and wall
      motion score index was improved in patients at rest and after exercise,
      indicating that descent to the Dead Sea in patients with coronary disease is
      safe, improves exercise performance, and decreases ischemia.

PMID- 10073829
TI  - Referral patterns to a University-based cardiac rehabilitation program.
AB  - Referral rates to our cardiac rehabilitation program among patients hospitalized
      for coronary heart disease were computed over an 18-month period. Only 8.7% of
      eligible patients were referred, suggesting that more education targeting
      physicians, patients, and insurers is needed and barriers to participation must
      be systematically addressed.

PMID- 10073830
TI  - The Selvester 32-point QRS score for evaluation of myocardial infarct size after
      primary coronary angioplasty.
AB  - In patients treated successfully with primary angioplasty for a first myocardial
      infarction, the Selvester 32-point score correlates well with infarct size
      measured with quantitative thallium-201 perfusion imaging. Therefore, it is a
      useful parameter for infarct sizing, particularly in patients with anterior
      infarction or reduced ejection fraction at discharge.

PMID- 10073831
TI  - Comparison of the polar maps method and the summed stress score for predicting
      outcome in medically treated patients with coronary artery disease.
AB  - This study showed that quantitative analysis of SPECT perfusion images provide
      comparable prognostic information to summed stress score in medically treated
      patients with coronary artery disease.

PMID- 10073832
TI  - Effects of dopamine and aminophylline on contrast-induced acute renal failure
      after coronary angioplasty in patients with preexisting renal insufficiency.
AB  - In phase 1 of this study, 60 patients undergoing coronary angioplasty were
      randomized to receive saline, dopamine, or aminophylline; the overall incidence
      of contrast-induced renal failure was 38%, without difference among the 3 groups.
      In phase 2 of this study, 72 patients with established contrast-induced renal
      failure were randomized to receive saline or dopamine; dopamine had a deleterious
      effect on the severity of renal failure, prolonging the course.

PMID- 10073833
TI  - Comparison of frequency of complications of implantable cardioverter
      defibrillators in children versus adults.
AB  - Compared with adults patients (n = 309) receiving implantable cardioverter
      defibrillators at the same institution, pediatric patients (n = 11) exhibited a
      trend toward lower defibrillation thresholds. At follow-up of 29 +/- 17 months,
      the incidence of recurrent arrhythmias was similar, but lead revisions and device
      infections were more common in the pediatric patients.

PMID- 10073834
TI  - QT interval and arrhythmic risk assessment after myocardial infarction.
AB  - To assess ventricular repolarization features as predictors of ventricular
      tachyarrhythmias (VT) in patients with previous myocardial infarction, we
      performed a dynamic study of QT interval from 24-hour electrocardiographic data.
      QT rate dependence was enhanced in patients with VT when compared with patients
      without VT.

PMID- 10073835
TI  - Effects of repeated electrical defibrillations on cardiac troponin I levels.
AB  - Multiple endocardial countershocks applied during intraoperative endocardial
      implantable cardioverter-defibrillator testing for the purpose of defibrillation
      threshold determination resulted in detectable myocardial injury in 5 of 12
      patients, as indicated by elevations in cardiac troponin I levels. This injury
      was not associated with acute changes on the surface electrocardiogram.

PMID- 10073836
TI  - Effective dose range of candesartan cilexetil for systemic hypertension.
      Candesartan Cilexetil Study Investigators.
AB  - The results of this randomized, double-blind, placebo-controlled, forced-dose
      titration study in a diverse population of hypertensive patients in the US
      indicate that candesartan cilexetil has clinically meaningful dose-related blood
      pressure-lowering effects and that maximum blood pressure reduction is achieved
      with doses of 16 and 32 mg given once daily. This study confirms that candesartan
      cilexetil is a highly effective antihypertensive agent with an excellent
      tolerability and safety profile, without dose-related adverse effects.

PMID- 10073837
TI  - Dynamic cyclic changes in coronary sinus caliber in patients with and without
      congestive heart failure.
AB  - M-mode echography of the coronary sinus in the apical 2-chamber view enabled us
      to measure coronary sinus caliber at specific phases of the cardiac cycle.
      Coronary sinus narrowing occurs consistently during atrial contraction, but is
      always absent in atrial fibrillation; in patients with congestive heart failure
      and systemic venous congestion, this narrowing is significantly attenuated.

PMID- 10073838
TI  - Exercise-induced hemoconcentration in heart failure due to dilated
      cardiomyopathy.
AB  - Exercise-induced hemoconcentration is a useful mechanism, particularly in heart
      failure, because it increases oxygen content of blood, perfusing the working
      muscles; in 50 normal subjects and 50 patients with congestive heart failure,
      hemoglobin at peak exercise increased by 7 +/- 3% and 5 +/- 3%, respectively.
      Hemoconcentration was due to fluid flux out of the vascular bed, likely through
      oncotic forces related to intracellular lactate accumulation and not to red blood
      cell recruitment from other organs (spleen), because hemoglobin increase, as a
      percentage, was similar to plasma protein increase.

PMID- 10073839
TI  - Histopathologic changes in asymptomatic relatives of patients with idiopathic
      dilated cardiomyopathy.
AB  - Echocardiographic screening of asymptomatic relatives of patients with idiopathic
      dilated cardiomyopathy identifies a subset with left ventricular enlargement who
      are assumed to have early familial idiopathic dilated cardiomyopathy. This study
      shows for the first time that the myocardium in such relatives demonstrates
      abnormal cellularity.

PMID- 10073840
TI  - Safety and efficacy of intravenous adenosine for pharmacologic stress testing in
      children with aortic valve disease or Kawasaki disease.
AB  - This study assessed the safety and efficacy of intravenous adenosine used as a
      coronary vasodilator in 18 pediatric patients with aortic valve disease or
      Kawasaki disease. Adenosine infusion effectively produced coronary vasodilation
      and was well tolerated.

PMID- 10073841
TI  - Intravenous versus subcutaneous vitamin K1 in reversing excessive oral
      anticoagulation.
AB  - Our data suggest that compared with the subcutaneous route of administration,
      intravenous vitamin K1 results in a more prompt reduction in the international
      normalized ration. However, for most patients, subcutaneous vitamin K1 is an
      effective and safe alternative when used in conjunction with modification of
      subsequent warfarin dosing, because virtually all patients achieved a safe level
      of anticoagulation within 72 hours with this route of administration.

PMID- 10073842
TI  - Comparison of cardiopulmonary responses in obese women using ramp versus step
      treadmill protocols.
AB  - The purpose of this study was to evaluate whether individual ramp protocol
      treadmill testing is superior to frequently used step protocols in eliciting peak
      cardiopulmonary responses in obese women. The main findings indicate that
      protocol selection based on predicted pretest individual exercise capacity is
      more important than whether a ramp or step protocol is used.

PMID- 10073843
TI  - Micromultiplane transesophageal echocardiographic probe for intraoperative study
      of congenital heart disease repair in neonates, infants, children, and adults.
AB  - This study reports the development of a micromultiplane 8.2-mm transesophageal
      echocardiographic probe. The probe is applicable to newborn infants and can
      deliver diagnostic images in adults.

PMID- 10073844
TI  - Elevation of high-density lipoprotein cholesterol in humans during long-term
      therapy with amiodarone.
AB  - The distribution of plasma lipids was studied in 18 patients receiving amiodarone
      for 18 months, confirming that amiodarone is associated with a 17% elevation in
      total cholesterol and, for the first time, documenting increases in high-density
      lipoprotein cholesterol. The increase in high-density lipoprotein was
      proportionately greater than that of low-density lipoprotein cholesterol,
      suggesting that the impact of changes in the predicted risk of coronary heart
      disease are less important than if the elevation consisted of low-density
      lipoprotein cholesterol alone.

PMID- 10073845
TI  - The Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery for
      Stable Angina: a continuing debate after 22 years.

PMID- 10073846
TI  - Comparison of the effects of losartan and captopril on mortality in patients
      after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in
      Myocardial Infarction with the Angiotensin II Antagonist Losartan.
AB  - Patients with acute myocardial infarction and evidence of heart failure or left
      ventricular dysfunction during the acute phase have an excessive mortality risk.
      Therapy with angiotensin-converting enzyme inhibitors attenuates the detrimental
      effects of angiotensin II and has been shown to substantially reduce morbidity
      and mortality in this population. Selective, angiotensin type 1 receptor
      antagonism with losartan, which inhibits the effects of angiotensin II regardless
      of its source at the receptor level, may provide more complete blockade of the
      renin-angiotensin system. The Optimal Therapy in Myocardial Infarction with the
      Angiotensin II Antagonist Losartan (OPTIMAAL) study is a multicenter, double
      blind, randomized, parallel, captopril-controlled trial. The primary hypothesis
      is that, compared with captopril, losartan will decrease the risk for all-cause
      mortality by 20% in high-risk patients after acute myocardial infarction. The
      study population will consist of 5,000 patients, > or = 50 years of age, with
      heart failure during the acute phase or with a new Q-wave anterior infarction or
      reinfarction. Patients will be randomized to treatment with either losartan or
      captopril. All patients will be followed until 937 deaths occur (event-driven).
      The primary end point is total mortality (all-cause mortality). The secondary and
      tertiary end points are sudden death (and/or resuscitated cardiac death) and
      fatal/nonfatal reinfarction. Based on the assumed event rate, treatment effect
      and a 95% power to detect a 20% reduction in all-cause mortality at the 4.3%
      significance level (2-sided, adjusted for 2 interim analyses), the trial will
      enroll at least 5,004 patients and continue until a total number of 937 events
      has been reached (intention-to-treat analysis).

PMID- 10073847
TI  - Support for the open-artery hypothesis in survivors of acute myocardial
      infarction: analysis of 11,228 patients treated with thrombolytic therapy.
AB  - We examined the possible benefits of achieving and maintaining infarct-related
      artery potency beyond the time when preservation of left ventricular function
      would be expected. The open-artery hypothesis suggests that a patent infarct
      related artery confers a survival benefit greater than that expected from
      myocardial salvage alone, which extends beyond the time when preservation of left
      ventricular function is expected. We examined the survival experience of patients
      undergoing thrombolysis in the Global Utilization of Streptokinase and TPA for
      Occluded Arteries (GUSTO-I) trial for whom data on the potency of the infarct
      artery were available. Univariable analysis was used to determine the unadjusted
      relations of angiographic variables and revascularization procedures to both 30
      day and 1-year mortality in 30-day survivors. Multivariable analysis was used to
      test for interactions between patency and each characteristic and to adjust both
      for all other variables and for baseline characteristics known to predict
      mortality. In both univariable and multivariable analysis, patients with an open
      rather than a closed infarct-related artery had significantly lower 30-day
      mortality (p <0.001). This benefit cannot be accounted for by myocardial salvage
      alone, because it remained after adjustment for left ventricular ejection
      fraction. Patency was also associated with lower 1-year mortality in 30-day
      survivors, but not after adjustment for other variables affecting late mortality.
      Having an open infarct-related artery at the time of first catheterization
      confers a survival advantage that extends beyond the benefit of myocardial
      salvage from thrombolytic therapy, and is independent of ejection fraction.

PMID- 10073848
TI  - Effects of revascularization after first acute myocardial infarction on the
      evolution of QRS complex changes (the DANAMI trial). DANish Trial in Acute
      Myocardial Infarction.
AB  - The changes in QRS complex morphology associated with acute myocardial infarction
      (AMI) can resolve spontaneously over time. Whether complete revascularization of
      the infarct-related myocardial territory after AMI affects this QRS resolution
      has not been studied adequately. The present study compares the evolution of the
      changes in the QRS complex associated with AMI during 1-year follow-up in
      patients treated with or without revascularization after their first thrombolyzed
      AMI. The study is a substudy of the DANish Trial in Acute Myocardial Infarction
      (DANAMI) (n = 1,008) that randomized patients with inducible ischemia after their
      first AMI, treated with intravenous thrombolytic therapy, to conservative
      treatment or coronary angiography followed by the appropriate revascularization
      strategy. A total of 817 patients had complete sets of evaluable
      electrocardiograms. Electrocardiograms were obtained at randomization, and at 3,
      6, and 12 months of follow-up and subjected to blinded core-laboratory evaluation
      according to the Selvester QRS scoring method. This score considers Q-, R-, and S
      wave duration and ratios to provide a semiquantitative estimate of AMI size. The
      median electrocardiographic estimated infarct size in the entire population was
      15% of the left ventricle at randomization. At the end of the follow-up period
      this estimate had decreased to 12% (p < 0.00001). There was no difference in the
      rate of QRS resolution whether the patients were subgrouped according to
      randomization or subgrouped according to actual treatment with or without
      revascularization. The present study confirms the findings from previous studies
      conducted in the prethrombolytic era, that considerable normalization of the QRS
      complex also occurs after AMI treated with thrombolytic therapy. This QRS
      normalization seems unaffected by an aggressive treatment strategy with
      revascularization via balloon angioplasty or bypass surgery.

PMID- 10073849
TI  - Association between percutaneous transluminal coronary angioplasty volumes and
      outcomes in the Healthcare Cost and Utilization Project 1993-1994.
AB  - Studies from a variety of settings have indicated that outcomes for coronary
      angioplasty are improved when performed in institutions with high caseloads (>
      400/year). The purpose of this investigation was to examine the volume outcome
      hypothesis for coronary angioplasty in a 20% stratified sample of acute care, non
      federal hospitals in 17 states. Data were derived from the Nationwide Inpatient
      Sample from the Health Care Cost and Utilization Project releases 2 and 3. From
      these records, 163,527 angioplasties from 214 hospitals were selected. Outcomes
      included hospital mortality, same-admission coronary artery bypass surgery, and a
      combined end point of either death or same-admission surgery, or both. Hospital
      volumes were defined as low (< or = 200 cases/year), medium (201 to 400), and
      high (> 400). Analyses were conducted separately for patients with and without a
      principal discharge diagnosis of acute myocardial infarction (AMI). For both AMI
      and no-AMI groups, the rates of adverse outcomes were generally lower in high
      volume institutions, and this finding was true in both univariate and
      multivariate analyses. Although 27% of hospitals were in the low-volume category,
      only 5% of all procedures were performed in these institutions. Projecting to all
      United States hospitals for the 2 years, if all procedures performed in low
      volume centers had been done in high-volume institutions, 137 deaths could have
      been averted (90 AMIs, 47 no-AMIs) as well as 404 (46 AMIs, 358 no-AMIs) same
      admission surgeries. The results of this study support the hypothesis that better
      results are obtained in higher volume institutions, but also show that in 1993
      and 1994, relatively few patients had their procedures performed in low-volume
      institutions.

PMID- 10073850
TI  - Procedural results and early clinical outcome of percutaneous transluminal
      myocardial revascularization.
AB  - A substantial number of patients present with medically refractory angina who are
      not candidates for angioplasty or bypass surgery. The creation of channels
      between the myocardium and the ventricular blood pool has been performed after
      thoracotomy with excellent relief of symptoms but has been associated with high
      perioperative mortality. We investigated the safety of a nonoperative,
      percutaneous technique for channel creation. Twenty-seven patients with angina
      and coronary anatomy not amenable to revascularization with coronary angioplasty
      or bypass surgery underwent percutaneous transluminal myocardial
      revascularization (PTMR). Energy from a Holmium:yttrium-aluminum-garnet (YAG)
      laser was directed through a fiber enclosed in a catheter to the ventricular
      myocardium creating channels between the blood pool and the myocardium. On
      average, 17 +/- 4 channels were formed per patient. There were no procedure
      related deaths, episodes of tamponade, or other complications except for an
      increase in creatine phosphokinase in 1 patient. Immediately after the procedure,
      there was no worsening of regional wall motion function in any patient, but
      rather improvement in some. All patients were discharged alive after a hospital
      stay of 1.8 +/- 1.5 days. Mean Canadian Cardiovascular Society functional class
      declined from 3.6 +/- 0.5 before the procedure to 0.65 +/- 0.8 at 30 days after
      the procedure (p < 0.01). For 12 patients eligible for 6-month follow-up, mean
      functional class was 0.94 +/- 0.97. At 6-month stress testing, 9 of these 12 had
      no electrocardiographic evidence of ischemia. Thus, PTMR can be performed safely
      in the cardiac catheterization laboratory with a complication rate lower than
      that reported in surgical series and with excellent near-term symptomatic relief.
      The long-term effect of PTMR on mortality and relief of angina as well as its
      safety and effectiveness compared with the surgical approach remains to be
      defined.

PMID- 10073851
TI  - Immediate results and late clinical outcomes after new CrossFlex coronary stent
      implantation.
AB  - This study evaluates the safety and efficacy of the new CrossFlex stent in the
      treatment of native coronary artery disease. The CrossFlex stent is a flexible,
      balloon-expandable new device with an excellent flexibility, radial strength,
      conformability, and radio-opacity. Little data are available concerning the
      clinical and angiographic outcomes of this device. The CrossFlex stent was
      implanted in 209 consecutive patients with 226 lesions. Follow-up angiography was
      performed at 6 months, and clinical evaluation was undertaken at regular
      intervals after stent implantation. Procedural success was achieved in all
      lesions without in-hospital complications. Angiographic follow-up data were
      available in 153 of the 187 eligible lesions (follow-up rate, 82%), and the
      overall angiographic restenosis rate was 16.3%. Minimal lumen diameter
      immediately after stent placement was the only predictor of angiographic
      restenosis. Clinical follow-up was obtained in all patients at 10.5 +/- 5.2
      months. There were 4 deaths (1 cardiac in origin, the others noncardiac in
      origin), and 1 nonfatal myocardial infarction (nonstented artery) during follow
      up. Target lesion revascularization was required in 15 patients (7%), and the
      overall event-free survival rate (death, myocardial infarction, and repeat
      revascularization) was 87% at the end of the follow-up period. The CrossFlex
      stent is a safe and effective device with a high procedural success rate, and a
      favorable late clinical outcome for treatment of native coronary artery disease.
      Further randomized trials are needed to compare the CrossFlex stent with standard
      slotted-tube stents.

PMID- 10073852
TI  - Comparison of controlled-onset, extended-release verapamil with amlodipine and
      amlodipine plus atenolol on exercise performance and ambulatory ischemia in
      patients with chronic stable angina pectoris.
AB  - This multicenter, randomized, double-blind, parallel group, placebo lead-in,
      placebo-controlled study compared the antianginal and anti-ischemic effects of
      once-daily bedtime dosing of controlled-onset extended-release (COER-24)
      verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients
      with chronic stable angina. A total of 551 patients with exercise-induced
      myocardial ischemia and evidence of coronary artery disease were randomized to a
      4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg
      titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10
      mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day
      in the A.M. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance
      testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic
      (Holter) monitoring were performed at the end of placebo lead-in and double-blind
      treatment. Each active treatment significantly improved symptom-limited exercise
      duration and time to moderate angina (p < or = 0.01 vs placebo). For patients
      with baseline ischemia, amlodipine resulted in a statistically significant
      increase in total duration of ischemic episodes compared with placebo, whereas
      COER-24 verapamil and amlodipine plus atenolol resulted in statistically
      significant decreases compared with placebo and amlodipine. Heart rate at onset
      of ischemic episodes and ST product were also significantly increased with
      amlodipine (p < 0.05) compared with either COER-24 or amlodipine plus atenolol.
      COER-24 and amlodipine alone or in combination with atenolol improved exercise
      capacity in patients with angina pectoris. COER-24 verapamil monotherapy or
      amlodipine plus atenolol combination therapy were more effective than amlodipine
      monotherapy in decreasing ambulatory myocardial ischemia, especially during the
      hours of 6 A.M. to 12 noon.

PMID- 10073853
TI  - Serum neopterin levels and the angiographic extent of coronary arterial narrowing
      in unstable angina pectoris and in non-Q-wave acute myocardial infarction.
AB  - Systemic serum markers of inflammation are elevated in diseases due to
      atherosclerosis, but have not been associated with the extent of atherosclerotic
      disease. We examined the role of neopterin, a byproduct of activated macrophage
      metabolism, in patients with unstable angina. Baseline neopterin samples and
      clinical histories were obtained in 52 patients admitted with unstable angina
      pectoris. Coronary angiograms of 27 patients were reviewed using Sullivan's
      method to assess the total atherosclerotic burden in the coronary arteries.
      Twenty-six of the 52 patients were eventually diagnosed with a non-Q-wave acute
      myocardial infarction (AMI) and had higher neopterin levels (10.1 +/- 6.7 vs 7.2
      +/- 4.0 nmol/L, p = 0.06) than patients with a final diagnosis of unstable
      angina. Patients with neopterin >8.7 were more likely to be diagnosed with a non
      Q-wave AMI (75% vs 39%, p = 0.035) and were more likely to have significantly
      more severe and extensive angiographically determined atherosclerosis than
      patients with low neopterin levels. Neopterin levels correlated with the score of
      atherosclerotic extension (Spearman's rank correlation coefficient 0.4807, p =
      0.034). This study demonstrates a correlation between immune cell activation and
      the extent of angiographically determined atherosclerosis and the degree of
      myocardial ischemia.

PMID- 10073854
TI  - Long-term prospective assessment of left ventricular thrombus in anterior wall
      acute myocardial infarction and implications for a rational approach to embolic
      risk.
AB  - To prospectively assess the predictive value of left ventricular (LV) thrombus
      anatomy for defining the embolic risk after acute myocardial infarction (AMI), 2
      comparable groups of patients with a first anterior AMI (group A, 97 thrombolysed
      patients; group B, 125 patients untreated with antithrombotic drugs [total 222])
      underwent prospective serial echocardiography (follow-up 39 +/- 13 months) at
      different time periods. LV thrombi were detected in 26 patients in group A (27%)
      and in 71 in group B (57%; p <0.005). Embolism occurred in 12 patients (5.4%; 1
      in group A [1%] vs 11% in group B [9%], p < 0.04). At multivariate analysis,
      thrombus morphologic changes were the most powerful predictor of embolism (p
      <0.001), followed by protruding shape (p <0.01) and mobility (p <0.02). In
      patients untreated with thrombolysis, a higher occurrence of thrombus morphologic
      changes (48% vs 8%, p <0.002) and protruding shape (69% vs 31%, p <0.002) were
      observed, whereas thrombus mobility was similar in the 2 groups (18% vs 8%, p =
      NS). Thrombus resolution occurred more frequently in thrombolysed patients (85%
      vs 56%, p <0.002). Thus, after anterior AMI, changes in LV thrombus anatomy
      frequently occur and appear the most powerful predictor of embolization. A minor
      prevalence of thrombus, a more favorable thrombus anatomy, and a higher
      resolution rate may contribute to reduce embolic risk after thrombolysis.

PMID- 10073855
TI  - Value of additional two-hour myoglobin for the diagnosis of myocardial infarction
      in the emergency department.
AB  - Myoglobin has been described as an early marker of myocardial injury. It
      increases within 1 to 3 hours of myocardial injury, and falls back to normal
      early after the event. Few data suggest that myoglobin can be used to triage
      patients with chest pain. To assess the diagnostic utility of second myoglobin
      levels drawn within 2 to 3 hours after presentation to the emergency department
      for detecting myocardial infarction, we prospectively collected myoglobin levels
      in 368 patients aged > or = 30 years who were admitted with chest pain. Myoglobin
      levels were measured at admission and 2 to 3 hours later. Sensitivity and
      specificity for detecting acute myocardial infarction for a twofold increase in
      myoglobin level from baseline were 39% and 98%, respectively. The early
      diagnostic performance of myoglobin at admission, the second level drawn 2 to 3
      hours later, and creatine kinase-MB mass drawn at admission were similar
      (receiver-operating characteristic curves 0.80, 0.86, and 0.85). The diagnostic
      performance of each of these markers was significantly superior to the absolute
      change from baseline to second myoglobin (receiver-operating characteristic curve
      0.77). In patients who presented within 4 hours of symptom onset, myoglobin drawn
      2 to 3 hours later had the highest yield for detecting myocardial infarction.
      These results suggest that serial myoglobin measurement aiming to detect changes
      over time is not superior to single marker determinations. Myoglobin measured in
      2 to 3 hours from admission may be helpful in triaging patients who present
      within 4 hours from onset of symptoms.

PMID- 10073856
TI  - Association of exercise-induced ventricular ectopic activity with thallium
      myocardial perfusion and angiographic coronary artery disease in stable, low-risk
      populations.
AB  - This study sought to determine the association of exercise-induced ventricular
      ectopic activity with thallium perfusion defects and severity of angiographic
      coronary artery disease (CAD). Two cohorts consisting of adults without heart
      failure or known severe ventricular ectopic activity at rest were studied. The
      first cohort consisted of adults (n = 2,743) who underwent maximum exercise
      thallium stress testing. The second cohort consisted of adults (n = 423) who
      underwent coronary angiography within 90 days of treadmill testing. Significant
      exercise-induced ventricular ectopic activity was defined as frequent ventricular
      premature complexes or nonsustained ventricular tachycardia. Severe CAD was
      defined as left main CAD (> or = 50% stenosis), 3-vessel CAD (> or = 70%
      stenosis), or 2-vessel CAD with > or = 70% stenosis of the proximal left anterior
      descending artery. In the thallium cohort, exercise-induced ventricular ectopic
      activity was associated with a greater frequency of thallium defects (35.2% vs
      18.7%, odds ratio [OR] 2.35, 95% confidence intervals [CI] 1.62 to 3.42, p
      <0.001); after adjusting for possible confounders, this association persisted
      (for any defect adjusted OR 1.66, 95% CI 1.09 to 2.53, p = 0.02; for septal
      defect adjusted OR 2.77, 95% CI 1.51 to 5.07, p <0.001). There was no association
      between exercise-induced ventricular ectopic activity and mortality during 2
      years of follow-up. In the angiographic cohort, there was no association of
      exercise-induced ventricular ectopy with severe CAD (19% vs 20%, OR 0.93, 95% CI
      0.41 to 2.09, p = NS). Exercise-induced ventricular ectopic activity was
      associated with a greater likelihood of thallium perfusion defects, but was not
      associated with angiographic severity of coronary disease or with short-term
      mortality.

PMID- 10073857
TI  - Determinants of pulmonary venous flow reversal in mitral regurgitation and its
      usefulness in determining the severity of regurgitation.
AB  - Pulmonary venous flow (PVF) reversal is observed in mitral regurgitation (MR) and
      can be detected by Doppler echocardiography. However, the determinants of PVF
      alterations in MR have not been analyzed with simultaneous quantitative methods,
      and the diagnostic accuracy of flow reversal is uncertain. Prospectively, in 128
      patients with isolated MR of various degrees (regurgitant fraction 4% to 81%),
      Doppler echocardiography was used to measure PVF velocity simultaneously to
      quantify MR by 2 methods and to perform a comprehensive hemodynamic assessment.
      Systolic PVF velocity was 4 +/- 56 cm/s (systolic flow reversal in 39 patients)
      and showed the strongest correlations with mitral effective regurgitant orifice
      (r = -0.56, p <0.0001). In multivariate analysis, larger effective regurgitant
      orifice (p <0.0001), eccentric jets (p = 0.0023), longer jets (p = 0.0033), and
      lower mitral regurgitant velocity (p = 0.0015) were independent determinants of
      decreased systolic PVF velocity. In organic MR, increased filling pressures were
      associated with systolic PVF reversal. Blunted systolic flow was associated with
      shorter mitral deceleration time (p <0.0001) and enlarged left atrium (p =
      0.0007). For the diagnosis of severe MR (regurgitant orifice > or = 35 mm2,
      regurgitant fraction > or = 50%), systolic flow reversal sensitivity was 61% and
      60%, and specificity was 92% and 85%, respectively. Among 29 patients in whom
      surgery demonstrated severe mitral lesions, 12 (41%) had no systolic flow
      reversal preoperatively. In patients with MR, the determinants of systolic PVF
      are complex and, in addition to the degree of MR, include the hemodynamic
      consequences of MR, jet characteristics, left ventricular filling, and left
      atrial volume alterations. Consequently, systolic PVF reversal is a useful sign
      of severe MR but of relatively low sensitivity, emphasizing the importance of
      quantifying MR.

PMID- 10073858
TI  - Usefulness of the indexed effective orifice area at rest in predicting an
      increase in gradient during maximum exercise in patients with a bioprosthesis in
      the aortic valve position.
AB  - This study examines the hemodynamic behavior of aortic bioprosthetic valves
      during maximum exercise. Nineteen patients with a normally functioning stented
      bioprosthetic valve and preserved left ventricular function were submitted to
      maximum ramp bicycle exercise. In 14 of the 19 patients, valve effective orifice
      area and mean gradient were measured at rest and during exercise using Doppler
      echocardiography. At peak exercise (mean maximal workload 118 +/- 53 W), the
      cardiac index increased by 122 +/- 34% (+3.18 +/- 0.71 L/min/ m2, p <0.001),
      whereas mean gradient increased by 94 +/- 49% (+12 +/- 8 mm Hg, p <0.001), and
      effective orifice area by 9 +/- 13% (+0.15 +/- 0.22 cm2, p = 0.02). A strong
      correlation was found between the increase in mean gradient during maximum
      exercise and the valve area at rest indexed for body surface area (r = 0.84, p
      <0.0001). Due to the increase in valve area, the increase in gradient was less (
      9 +/- 7 mm Hg, -41 +/- 33%, p = 0.0006) than theoretically predicted assuming a
      fixed valve area. These results suggest that the effective orifice area of the
      bioprostheses has the capacity to increase during exercise; therefore, limiting
      the increase in gradient. The relation found between the indexed effective
      orifice area at rest and the increase in gradient during exercise should be
      useful in predicting the hemodynamic behavior of a stented bioprosthesis during
      exercise.

PMID- 10073859
TI  - Influence of left ventricular cavity size on clinical presentation in
      hypertrophic cardiomyopathy.
AB  - The aim of this study was to assess whether left ventricular (LV) cavity size
      relates to functional impairment and syncope in patients with hypertrophic
      cardiomyopathy (HC). LV diastolic dysfunction influences functional limitation in
      HC. A reduced LV end-diastolic dimension may underlie impaired diastolic
      properties and be implicated in hemodynamic syncope. Eighty-two consecutive
      patients with HC (off drugs, in sinus rhythm) underwent echocardiography to
      measure LV end-diastolic dimension in the short-axis view (indexed to the body
      surface area) and radionuclide angiography (n = 50) to calculate peak filling
      rate (normalized to stroke counts/s). Patients in New York Heart Association
      functional classes II to IV had smaller LV end-diastolic dimension (23.2 +/- 2.6
      vs 25.5 +/- 2.5 mm/M2, p = 0.0001) and lower peak filling rate (4.3 +/- 1.4 vs
      5.1 +/- 1.3 stroke counts/s, p = 0.036) than those in New York Heart Association
      class I. LV end-diastolic diameter was correlated to peak filling rate (r = 0.37;
      p = 0.008). The most potent predictors of functional limitation were LV end
      diastolic dimension (relative risk [RR] 0.63, confidence interval [CI] 0.45 to
      0.88; p = 0.008), age (RR 1.09, CI 1.03 to 1.17; p = 0.003), and LV thickness
      score (RR 1.08, CI 1.02 to 1.13; p = 0.003). LV cavity size was smaller in
      patients with functional limitation irrespective of obstruction and hypertrophy.
      Patients with differed from those without a history of syncope for a smaller LV
      end-diastolic dimension (23.2 +/- 2.5 vs 25.0 +/- 2.7 mm/M2, p = 0.008), which
      was the only independent predictor of syncope (RR 0.77, CI 0.63 to 0.95; p =
      0.013). Thus, a small LV cavity size is associated with functional limitation and
      history of syncope in HC.

PMID- 10073860
TI  - Rapid return of left ventricular outflow tract obstruction and symptoms following
      cessation of long-term atrioventricular synchronous pacing for obstructive
      hypertrophic cardiomyopathy.
AB  - Atrioventricular (AV) synchronous pacing reduces left ventricular (LV) outflow
      tract obstruction and symptoms in patients with obstructive hypertrophic
      cardiomyopathy (HC). The duration of gradient reduction, if pacing is
      discontinued for a prolonged period of time, is unknown. This question is
      addressed in the present randomized double-blind crossover study comparing
      continued with inactivated pacing. Ten patients, successfully paced for > or = 6
      months, were randomized to continue pacing or to have their pacemakers
      inactivated after baseline examinations, including echo-Doppler imaging, exercise
      testing, and a quality-of-life questionnaire. When entering the study, the
      patients were in New York Heart Association functional classes I to II. After
      pacemaker programming, examinations were repeated at 1, 4, and 12 weeks. At the
      12-week follow-up the alternate pacing mode was programmed, and the patient
      entered the second study arm. Premature pacemaker pacing occurred if severe
      clinical deterioration or a significant increase of the LV outflow tract
      obstruction were evident. Three patients started in the inactive mode and 7
      patients in the active mode. All patients who started with the pacemaker
      inactivated required early reprogramming due to return of symptoms after 7, 10,
      and 13 days, respectively. All 7 patients who started in the active pacing mode
      completed the first period; however, after reprogramming to the inactive mode
      they required early activation after 1 to 20 days due to reappearance of
      intolerable subjective symptoms. The LV outflow tract gradient increased
      significantly after inactivation of pacing in all patients (22 +/- 21 mm Hg to 47
      +/- 21 mm Hg). Thus, AV synchronous pacing effectively relieves symptoms and
      reduces the LV outflow tract gradient in patients with obstructive HC. This
      improvement, which is rapidly established with the initiation of cardiac pacing,
      is not persistent after cessation of pacing. Reinitialization of pacing promptly
      reduces the LV outflow tract obstruction and relieves symptoms to a preexisting
      extent.

PMID- 10073861
TI  - Postsurgical course of patients with congenitally corrected transposition of the
      great arteries.
AB  - Because congenitally corrected transposition is a rare congenital anomaly, little
      is known about the prognosis of patients with this syndrome. The present study
      evaluated the functional status and clinical course of 73 patients (42 male and
      31 female) aged 10 days to 73 years. Follow-up was 1 week to 37 years (mean 12.7
      years). Particular attention was paid to the systemic right ventricle,
      considering the current controversies about long-term right ventricular function.
      Survival of patients with this condition in general was significantly below
      normal. The total mortality rate was 11% (8 patients) after a mean follow-up of
      12.7 years (range 10 days to 37 years). Mean age at death was 18.5 years (range 6
      days to 63 years). The mean age of the survivors at latest follow-up was 21.4
      years (range 4 months to 73 years). In most patients, right ventricular function
      deteriorated and tricuspid valve regurgitation increased, which began at a very
      young age. Patients without associated lesions developed complications at a
      higher age compared with the total group. Right ventricular and tricuspid
      valvular function deteriorated more frequently in patients following intracardiac
      operation (28% and 52%, respectively) compared with patients undergoing
      palliative intervention (16%) or no surgery at all (28%). We conclude that
      survival of patients with this condition is substantially reduced compared with
      the natural history of an age- and gender-matched general population. This could
      be explained by the associated cardiac defects, but also by the anatomic
      condition itself.

PMID- 10073862
TI  - Impact of arrhythmia circuit cryoablation during Fontan conversion for refractory
      atrial tachycardia.
AB  - Refractory atrial arrhythmias in late postoperative Fontan patients are usually
      associated with residual hemodynamic abnormalities and result in significant
      morbidity and mortality. Surgical revision of the Fontan anastomosis may improve
      hemodynamics without eliminating tachycardia. This study sought to assess the
      impact of surgical cryoablation of the arrhythmia circuit at the time of Fontan
      conversion on the clinical recurrence of tachycardia. Sixteen consecutive
      atriopulmonary Fontan patients with refractory atrial arrhythmias underwent
      surgical conversion to lateral tunnel total cavopulmonary anastomosis (15) or
      Fontan revision (1 patient). The initial 4 patients underwent Fontan conversions
      alone, without specific arrhythmia surgery. The subsequent 12 patients underwent
      electrophysiologically guided cryoablation of the tachycardia circuits at the
      time of surgical conversion. The mean age at Fontan revision was 15.6 +/- 3.8
      years. Cryoablation was directed to 3 identified major tachycardia circuits: the
      inferomedial right atrium, the superior rim of the prior atrial septal defect
      patch, and along the lateral right atrial wall. Transmural antitachycardia
      pacemakers were implanted in 11 of the 16 patients. There was no surgical
      mortality in either group, and all patients improved in functional
      classification. All patients not undergoing cryoablation experienced recurrent
      symptomatic tachycardia requiring antiarrhythmic therapy (median follow-up, 54
      months) versus 2 of 12 patients receiving cryoablation (median follow-up, 25
      months; p <0.02). Thus, surgical cryoablation of the arrhythmia circuit at the
      time of Fontan conversion is highly effective in the management of refractory
      atrial arrhythmias, and is superior to Fontan conversion alone.

PMID- 10073863
TI  - Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT)
      pilot study.
AB  - The primary objectives of the pilot study were to: (1) evaluate the feasibility
      of recruiting patients with peripheral arterial disease (PAD); (2) measure the
      efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low
      density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic
      therapy, and their combinations; and (3) assess adherence to a complex multiple
      drug regimen. Secondary objectives included measurement of the effect of the
      interventions on prespecified biochemical markers, maintenance of therapy masking
      (in particular with niacin), and measurement of the intervention's impact on
      functional status and on quality of life. To date, no secondary prevention trial
      has been conducted specifically among patients with PAD. Intermittent
      claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a
      striking increase in incidence of PAD with age, particularly among those aged >50
      years in both sexes, although men are twice as likely as women to develop PAD.
      The Arterial Disease Multiple Intervention Trial was a double-blind randomized
      pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design
      was used to evaluate the effect of 3 interventions. The pilot incorporated
      several major novel design features: first, the use of a simple noninvasive
      method (measurement of ankle brachial index) to identify a population with either
      symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to
      increase HDL with nicotinic acid in the intervention group while lowering LDL
      levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as
      needed in the intervention and control group. Two other arms, the antioxidant arm
      (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm
      (using warfarin) were also added. Adherence to therapy was measured by pill
      count, and success in treatment was measured by the proportion of values in
      target range for HDL, LDL, and the international normalized ratio.

PMID- 10073864
TI  - Erectile dysfunction and sildenafil citrate and cardiologists.
AB  - Since the release of sildenafil citrate (Viagra), increasing numbers of patients
      are seeking treatment for erectile dysfunction (ED). Many of the risk factors for
      ED are the same as those for cardiac disease. Sildenafil citrate is a highly
      effective oral agent for ED. It is absolutely contraindicated in patients
      receiving organic nitrates. The issue of cardiac deaths associated with
      sildenafil citrate and ways of potentially minimizing these cases are discussed.

PMID- 10073865
TI  - Correlation of serum lipoprotein(a) with the angiographic and clinical
      presentation of coronary artery disease.
AB  - This study reports the association of elevated serum lipoprotein(a) levels with
      angiographically extensive coronary disease and the presence of totally occluded
      coronary arteries, as well as the association of elevated lipoprotein(a) with
      unstable angina. These results support the role of lipoprotein(a) in the human
      atherothrombotic process.

PMID- 10073866
TI  - Exercise-induced myocardial ischemia triggers the early phase of preconditioning
      but not the late phase.
AB  - The aim of the present study was to establish whether exercise-induced ischemia
      triggers the second window of protection in 15 patients with coronary artery
      disease undergoing 2 consecutive treadmill exercise tests and a third test 24
      hours later. Our findings confirm that a first exercise-induced ischemic
      challenge induces the early phase of preconditioning but not the late phase, thus
      suggesting that either a late protective effect of preconditioning does not exist
      in the setting of demand ischemia or, if it exists, it must be weaker than the
      early protective effect.

PMID- 10073867
TI  - Reappraisal of the Norris score and the prognostic value of left ventricular
      ejection fraction measurement for in-hospital mortality after acute myocardial
      infarction.
AB  - A retrospective analysis of all patients admitted to an academic suburban
      hospital with a diagnosis of acute myocardial infarction was performed to
      evaluate the usefulness of the addition of left ventricular ejection fraction to
      the Norris score in predicting in-hospital mortality. Although both the Norris
      score and ejection fraction predicted mortality in univariate analysis,
      multivariate logistic regression analysis revealed only 3 independent variables:
      ejection fraction, age, and admission systolic blood pressure, which are
      incorporated to form a new simplified scoring system.

PMID- 10073869
TI  - Effect of beta-adrenergic blocker therapy on the circadian rhythm of heart rate
      variability in patients with chronic stable angina pectoris.
AB  - The circadian rhythm of heart rate variability is present in normal subjects and
      in patients with angina, with the greatest variation in the normal population and
      a smaller but significant variation in the anginal group. With beta-adrenergic
      blockade, significant improvement occurs in all daytime time domain parameters,
      nocturnal percentage of RR intervals with >50-ms variation, and square root of
      mean-squared differences of successive RR intervals, daytime total power, and
      high-frequency band, representing significant improvement in parasympathetic
      function.

PMID- 10073868
TI  - Comparison of response to serotonin of radial artery grafts and internal mammary
      grafts to native coronary arteries and the effect of diltiazem.
AB  - We studied the response of radial artery (RA) or left internal mammary artery
      grafts to the intraluminal infusion of serotonin in 22 consecutive patients 1
      year after the operation, subsequently evaluating the effect of diltiazem in 9
      patients. Serotonin causes a significant vasoconstriction of the RA grafts, but
      not of the left internal mammary artery grafts, whereas oral diltiazem treatment
      does not prevent the effect of the higher dose of serotonin on RA grafts.

PMID- 10073870
TI  - Comparison of frequency of new coronary events in older subjects with and without
      valvular aortic sclerosis.
AB  - In a prospective study of 1,980 subjects (mean age 81 +/- 8 years) without
      valvular aortic stenosis, 981 (50%) had valvular aortic sclerosis diagnosed by 2
      dimensional and continuous-wave Doppler echocardiography. Independent risk
      factors for new coronary events were prior coronary artery disease (p = 0.0001,
      risk ratio 2.8), male gender (p = 0.002, risk ratio 1.3), and valvular aortic
      sclerosis (p = 0.0001, risk ratio 1.8).

PMID- 10073871
TI  - Effect of right ventricular pacing in patients with complete left bundle branch
      block.
AB  - The relation between left ventricular electromechanical delay and the acute
      hemodynamic effect of right ventricular pacing was studied in heart failure
      patients with and without complete left bundle branch block. Whereas right
      ventricular pacing provided a shorter electromechanical delay that correlated
      with an improvement in left ventricular function in patients with left bundle
      branch block, the converse was observed in patients without left bundle branch
      block.

PMID- 10073872
TI  - Resumption of motor vehicle operation in vasovagal fainters.
AB  - This study surveyed current practice patterns with respect to the manner by which
      cardiac arrhythmia specialists advise patients with vasovagal syncope regarding
      resumption of motor vehicle operation. Among 66 physician-respondents from 9
      countries, 98% indicated that they rely on tilt-table testing to establish a
      diagnosis, and, if an effective treatment is found based on serial tilt-table
      testing, they recommend a 6- to 7-week symptom-free waiting period before
      advising return to driving.

PMID- 10073873
TI  - Long-term outcome in patients with chronic atrial fibrillation after successful
      internal cardioversion.
AB  - Internal cardioversion is safe and effective in restoring sinus rhythm, even in
      patients with persistent AF of prolonged duration. Up to 40% to 50% of patients
      with AF lasting >1 year but <3 years could be maintained in sinus rhythm using a
      class III antiarrhythmic drug after successful internal cardioversion, and
      amiodarone appears to be more effective than sotalol in this patient population.

PMID- 10073874
TI  - The "telepress" system for self-measurement and monitoring of blood pressure (the
      "SHAHAL" experience in Israel).
AB  - No "white coat" effect contaminated the validity of measurements in 30
      participants in a "Telepress" program, in which subscribers to a telecardiologic
      facility transtelephonically transmit their self-measured blood pressure values.

PMID- 10073875
TI  - Loss of bone mineral in patients with cachexia due to chronic heart failure.
AB  - We studied body composition and cytokine levels in 58 patients with heart failure
      and 16 control patients using dual-energy x-ray absorptiometry. Bone mineral
      content and density, and lean and fat tissue content, were reduced in cachectic
      compared with noncachectic patients and control subjects, with negative relations
      between indexes of bone composition and tumor necrosis factor and tumor necrosis
      factor receptor 1.

PMID- 10073876
TI  - Impact of home health care on health care costs and hospitalization frequency in
      patients with heart failure.
AB  - This study was undertaken to investigate the costs of delivering home health care
      services to patients with heart failure and the impact of these services on
      hospitalization frequency. Results suggest that referring patients with heart
      failure to home health care is costly and does not necessarily reduce
      hospitalization frequency.

PMID- 10073877
TI  - Predictive value of prominent right atrial V waves in assessing the presence and
      severity of tricuspid regurgitation.
AB  - Neither "prominent" right atrial V waves nor an elevated mean right atrial
      pressure reliably predicts the presence of moderate or severe tricuspid
      regurgitation. On the other hand, the absence of prominent right atrial V waves
      and an elevated mean right atrial pressure are relatively specific for the
      absence of moderate or severe tricuspid regurgitation.

PMID- 10073878
TI  - Effects of exercise on Doppler-derived pressure difference, valve resistance, and
      effective orifice area in different aortic valve prostheses of similar size.
AB  - The effects of increased transvalvular volume flow on Doppler-derived
      measurements were compared in similarly sized, normally functioning, mechanical
      prostheses, stented and stentless porcine bioprostheses, and homografts.
      Homograft and stentless valves showed the largest effective orifice area and the
      lowest pressure differences and valve resistance at rest and during exercise
      induced increase in flow rates.

PMID- 10073879
TI  - Use of percutaneous cardiopulmonary support of patients with fulminant
      myocarditis and cardiogenic shock for improving prognosis.
AB  - Percutaneous cardiopulmonary support was used in 9 patients with fulminant
      myocarditis and cardiogenic shock. Although 2 of the patients died, 7 improved
      and were able to resume social activities. Percutaneous cardiopulmonary support
      should be administered routinely to patients with fulminant myocarditis
      developing into cardiogenic shock.

PMID- 10073880
TI  - Comparison of phenotypic expression of hypertrophic cardiomyopathy in patients
      from the United States and Germany.
AB  - A comparison of patients with hypertrophic cardiomyopathy in the United States
      and Germany showed significant differences in phenotypic expression. While it is
      unresolved whether these observed morphologic differences were due to racial and
      genetic factors, or alternatively to patient selection, the awareness of such
      heterogeneity in the phenotypic expression of HC is relevant to interpreting
      clinical studies from different regions of the world.

PMID- 10073881
TI  - Accuracy of surface electrocardiograms for differentiating children with
      hypertrophic cardiomyopathy from normal children.
AB  - Most patients with hypertrophic cardiomyopathy have abnormal electrocardiograms.
      In this study of 37 matched pairs in the pediatric age group, the 12-lead
      electrocardiogram did not differentiate between affected and normal children
      reliably enough to allow it to be used as a screening test in the general
      population.

PMID- 10073882
TI  - Transvenous approach to coronary angiography in infants with tetralogy of Fallot.
AB  - A new technique is offered for selective imaging of the coronary arterial system
      from a transvenous approach in patients with tetralogy of Fallot as an
      alternative to other traditional approaches. This technique should identify
      important coronary anomalies while avoiding femoral arterial cannulation and
      compromise.

PMID- 10073883
TI  - Mechanism of sustained monomorphic ventricular tachycardia in systemic sclerosis.
AB  - Three patients with advanced systemic sclerosis and recurrent or incessant
      monomorphic ventricular tachycardia underwent cardiac electrophysiologic studies.
      Biventricular transcatheter mapping showed findings most compatible with a
      reentrant mechanism, which was effectively treated with transcatheter ablation.

PMID- 10073885
TI  - Obtaining and maintaining an ideal body weight.

PMID- 10073884
TI  - Leila Denmark, MD: practicing medicine at age 100.
AB  - Leila Denmark, MD, continues to practice medicine at age 100. Her lifestyle and
      work ethic are an inspiration in the current era of managed care mania.

PMID- 10073886
TI  - Management of pericardial effusion: safety over novelty.

PMID- 10073887
TI  - Absence of thrombotic thrombocytopenic purpura following coronary stenting in the
      ticlopidine era.

PMID- 10073888
TI  - Effects of aspirin on angiotensin-converting enzyme inhibition and left
      ventricular dilation one year after acute myocardial infarction.

PMID- 10073889
TI  - Ergonovine echocardiography for the diagnosis of coronary vasospasm.

PMID- 10073890
TI  - Macronutrient-specific dietary selection in rodents and its neural bases.
AB  - The only evidence for nutrient selection comes from baseline or treatment effects
      on nutrient intakes that are qualitatively similar when sensorily contrasting
      forms of each macronutrient are investigated and/or dietary compositions and
      strains of rat or mouse are different within or between laboratories. By that
      criterion the only potential case of a treatment reliably altering macronutrient
      selection identified in the present review of the literature is d
      norfenfluramine, fluoxetine and paraventricular serotonin (5-HT) reducing the
      intake of dextrin-containing diets at early dark. The only clear example of
      reverse effects of an agonist and an antagonist on dietary intake was found with
      serotonergic agents. Claims for catecholaminergic or opioid involvement in
      protein intake and peptidergic involvement in carbohydrate intake were not
      substantiated. There remain the issues of which learnt macronutrient-specific
      postgastric actions and sensory cues from the affected diet rely on the neural
      pathway(s) on which the drug is acting to alter dietary selection. Until
      experiments address these questions, the neural bases of nutrient-specific
      appetites will remain unknown. Drug effects must be consistent across differently
      textured and flavoured versions of each macronutrient tested.

PMID- 10073891
TI  - Transcutaneous cranial electrical stimulation (TCES): a review 1998.
AB  - The Transcutaneous Cranial Electrical Stimulation (TCES) technique appeared at
      the beginning of the 1960s and is aimed to act at the level of the central
      nervous system. The current, composed of high frequency pulses interrupted with a
      repetitive low frequency, is delivered through three electrodes (a negative
      electrode placed between the eyebrows while two positive electrodes are located
      in the retro-mastoid region). Due to the characteristics of the current
      delivered, shortcomings encountered with previous electrical stimulation
      techniques are avoided. The main property of TCES is to potentiate some drug
      effects, especially opiates and neuroleptics, during anesthetic clinical
      procedures. This potentiation effect permits drastic reduction of pharmacological
      anesthetic agent and reduces post-operative complications. Animal studies
      performed with TCES demonstrated that this stimulation releases 5-hydroxy-indol
      acetic acid and enkephalins. Despite numerous clinical and animal studies
      performed with this technique for several decades, TCES mechanisms are not
      completely elucidated but results obtained without undesirable effect are
      encouraging signs to continue investigations of this particular technique.

PMID- 10073892
TI  - 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans.
AB  - The 3,4-methylenedioxy analogues of amphetamine [MDMA ("Ecstasy", "Adam"), MDA
      ("Love") and MDE ("Eve")] are recreational drugs that produce feelings of
      euphoria and energy and a desire to socialize, which go far to explain their
      current popularity as "rave drugs". In addition to these positive effects, the
      drugs are relatively inexpensive to purchase and have the reputation of being
      safe compared to other recreational drugs. Yet there is mounting evidence that
      these drugs do not deserve this reputation of being safe. This review examines
      the relevant human and animal literature to delineate the possible risks MDMA,
      MDA and MDE engender with oral consumption in humans. Following a summary of the
      behavioral and cognitive effects of MDMA, MDA and MDE, risks will be discussed in
      terms of toxicity, psychopathology, neurotoxicity, abuse potential and the
      potential for drug-drug interactions associated with acute and chronic use.

PMID- 10073893
TI  - Neural pathway from the olfactory bulbs regulating tonic gonadotropin secretion.
AB  - Removal of the olfactory bulbs of male golden hamsters results in a marked
      increase in tonic gonadotropin, prolactin and testosterone secretion which
      counteracts inhibitory effects of manipulations such as maintenance on short
      photoperiod, food restriction or treatment with gonadal steroids. The bulbectomy
      induced increase in hormone secretion is interpreted to reflect a tonic
      inhibitory influence of the olfactory bulbs. This inhibition is not dependent
      upon chemosensory stimulation and may be mediated by olfactory bulb fibers
      projecting through the lateral olfactory tract to or through the olfactory
      tubercle. This review will relate these studies conducted on hamsters to results
      in other species, such as the rat, where the olfactory bulbs enhance serum
      gonadotropin levels.

PMID- 10073894
TI  - Are we dependent upon coffee and caffeine? A review on human and animal data.
AB  - Caffeine is the most widely used psychoactive substance and has been considered
      occasionally as a drug of abuse. The present paper reviews available data on
      caffeine dependence, tolerance, reinforcement and withdrawal. After sudden
      caffeine cessation, withdrawal symptoms develop in a small portion of the
      population but are moderate and transient. Tolerance to caffeine-induced
      stimulation of locomotor activity has been shown in animals. In humans, tolerance
      to some subjective effects of caffeine seems to occur, but most of the time
      complete tolerance to many effects of caffeine on the central nervous system does
      not occur. In animals, caffeine can act as a reinforcer, but only in a more
      limited range of conditions than with classical drugs of dependence. In humans,
      the reinforcing stimuli functions of caffeine are limited to low or rather
      moderate doses while high doses are usually avoided. The classical drugs of abuse
      lead to quite specific increases in cerebral functional activity and dopamine
      release in the shell of the nucleus accumbens, the key structure for reward,
      motivation and addiction. However, caffeine doses that reflect the daily human
      consumption, do not induce a release of dopamine in the shell of the nucleus
      accumbens but lead to a release of dopamine in the prefrontal cortex, which is
      consistent with caffeine reinforcing properties. Moreover, caffeine increases
      glucose utilization in the shell of the nucleus accumbens only at rather high
      doses that stimulate most brain structures, non-specifically, and likely reflect
      the side effects linked to high caffeine ingestion. That dose is also 5-10-fold
      higher than the one necessary to stimulate the caudate nucleus, which mediates
      motor activity and the structures regulating the sleep-wake cycle, the two
      functions the most sensitive to caffeine. In conclusion, it appears that although
      caffeine fulfils some of the criteria for drug dependence and shares with
      amphetamines and cocaine a certain specificity of action on the cerebral
      dopaminergic system, the methylxanthine does not act on the dopaminergic
      structures related to reward, motivation and addiction.

PMID- 10073895
TI  - Metabotropic glutamate receptors and the generation of locomotor activity:
      interactions with midbrain dopamine.
AB  - Interactions between excitatory amino acid (EAA) and dopamine (DA) pathways in
      the basal ganglia have been known for some time to contribute importantly to the
      generation of motor behaviors. In particular, the role played by ionotropic
      glutamate receptors (iGluRs) in such interactions and in the production of
      locomotion has received considerable attention, particularly in brain areas such
      as the ventral tegmental area (VTA) where EAA afferants are known to modulate the
      activity of DA neurons and the nucleus accumbens (NAcc) where descending EAA
      projections and ascending DA mesencephalic projections come in close apposition
      to each other and co-innervate intrinsic neurons projecting to motor output
      regions. Recently, the growing importance of the metabotropic glutamate receptor
      (mGluR) in the generation of motor behaviors and various forms of plasticity has
      begun to emerge. The known coupling of the mGluR to second messenger systems and
      its demonstrated role in the long-term modulation of synaptic transmission make
      it a logical candidate not only for the generation of locomotion involving EAA-DA
      interactions, but also for the induction and expression of locomotor plasticity
      involving these neurotransmitters. In this review, we examine the evidence
      supporting a role for mGluRs in the generation of DA-dependent locomotion as well
      as in one form of locomotor plasticity: the sensitization of locomotor activity
      by psychomotor stimulant drugs.

PMID- 10073896
TI  - Effects of centrally administered anxiolytic compounds in animal models of
      anxiety.
AB  - The effect of intra-cerebrally infused compounds in animal models of anxiety were
      reviewed. A large body of evidence suggested that benzodiazepine agonists in
      different brain regions--including areas of the raphe, hypothalamus,
      periaqueductal gray, septum, hippocampus, and amygdala--produce reasonably
      consistent anxiolytic effects in a variety of animal models. However, evidence
      regarding the effects on anxiety of 5-HT1A agonists, 5-HT2 compounds, and 5-HT3
      antagonists was somewhat less extensive, both anatomically and behaviourally, and
      more complex. For example, establishing receptor specificity for 5-HT ligand
      effects was often complicated by the lack of 'silent' and/or selective
      antagonists. Neuropeptides had significant effects on anxiety, but these were
      shown in a smaller number of animal models and in a limited number of brain
      regions. Regardless of the compounds tested, however, there seemed to be a
      surprising number of double dissociations (brain site by behavioural test). In
      fact in some instances, different fear reactions appeared to be controlled by
      distinct receptor subpopulations within particular parts of the limbic system.
      These results suggest that the neural control of anxiety might be analogous in
      organization to sensorimotor systems, i.e., anxiety is controlled by complex
      systems of multiple, distributed, parallel pathways.

PMID- 10073897
TI  - Informed consent to serum screening for Down syndrome: are women given adequate
      information?
AB  - To assess the information given to women during a maternal serum screening (MSS)
      programme, we prospectively applied a questionnaire to 504 pregnant women
      attending for amniocentesis after a screen-positive result. The survey based on
      200 usable questionnaires (39.7 per cent of our study population) showed that MSS
      was imposed as mandatory by 41.5 per cent of providers and done without their
      patients' agreement by 16 per cent. After release of the test results, 6.5 per
      cent of women believed that they were carrying a Down syndrome-affected fetus and
      21.5 per cent thought the risk was about 50-50. A total of 38.5 per cent of the
      pregnant women were not informed of the risk of miscarriage after amniocentesis
      and 67.5 per cent believed that there was no possibility of a false-negative
      result with MSS. Information given over the telephone was particularly poorly
      understood compared with information provided during an outcome visit, since
      women who learned of their test result during such a visit scored significantly
      higher (69 per cent) when questioned about the risk of carrying a Down syndrome
      affected fetus, compared with women informed of their test results by telephone
      (38.7 per cent) or by letter (47 per cent). We therefore suggest routine
      consultation with an antenatal care professional before testing to enable
      pregnant women to give their informed consent to MSS.

PMID- 10073898
TI  - First-trimester biochemical markers for Down syndrome.
AB  - The value of maternal serum pregnancy-associated protein A (PAPP-A), free and
      total beta human chorionic gonadotrophin (fbetahCG, betahCG) and alpha
      fetoprotein (AFP) in screening for Down syndrome (DS) in early pregnancy has been
      assessed. To evaluate the different biochemical markers, 32 DS pregnancies and
      267 controls were used for AFP, betahCG and PAPP-A. A subgroup of those (17 DS
      and 136 controls) were used to evaluate fbetahCG. All analytes were determined in
      fresh serum samples. Our results give support to the feasibility of maternal
      serum levels of PAPP-A as the best biochemical marker for DS in the first
      trimester, and either betahCG or fbetahCG as the second marker. No differences
      were found between betahCG and fbetahCG distribution levels as expressed as MoMs
      in normal and DS pregnancies in this study.

PMID- 10073899
TI  - Comparison of cell cultures, chromosome quality and karyotypes obtained after
      chorionic villus sampling and early amniocentesis with filter technique.
AB  - 548 cell cultures and karyotypes obtained by early amniocentesis with filtration
      technique (EAF) at a mean gestational age of 12 1/2 weeks were compared with 555
      obtained by transabdominal chorionic villus sampling (CVS) at a mean gestational
      age of 11 weeks. The number of abnormal karyotypes, culture failure rate and
      harvest time were evaluated. The results were then compared with three similar
      studies from the literature evaluating early amniotic fluid cultures obtained
      with conventional techniques compared with chorionic villus cultures. Further,
      the quality of the chromosome preparations from chorionic villi and early
      amniotic fluid respectively was compared. More abnormal karyotypes were found
      among the CVS cultures, which was expected due to earlier sampling and presence
      of confined placental mosaicism. No ambiguous results were present after EAF. The
      lowest culture failure rate of 0.2 per cent was found after EAF compared with 0.9
      per cent among CVS. EAF also showed a significantly lower culture failure rate
      when compared with the literature, where early amniocentesis (EA) had been
      carried out by standard techniques. The time from sampling to harvest was longer
      in the EAF group (mean 9.5 days) compared with CVS (mean 6.1 days), in accordance
      with the literature. Nevertheless, the culture time of EAF was significantly
      shorter than the mean of EA from the comparative studies, whereas CVS culture
      times showed no differences. Rates of pseudomosaicism, maternal cell
      contamination, single cell aberrations, number of chromosome bands, mitoses
      counted and number of primary cultures needed for each karyotype were also
      compared. We concluded that EAF carried out around 12 1/2 weeks of gestation is a
      successful method with a lower culture failure rate compared with CVS cultures
      from 11-week gestations and with a significantly lower culture failure rate when
      compared with EA from similar studies. EAF provides chromosome preparations of
      high quality, and the risk of ambiguous karyotypes is very low.

PMID- 10073900
TI  - Assaying the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a
      mitogen of immature cells in fetal blood cultures.
AB  - Based on the presence of immature cells in fetal blood, and in an attempt to
      shorten the cytogenetic reporting time, three simultaneous one-day culture
      regimes were established in 23 fetal blood samples: (a) the standard
      phytohemagglutinin (PHA)-stimulated lymphocytes culture, (b) a culture using the
      granulocyte-macrophage colony-stimulating factor (GM-CSF) as an alternative
      mitogen, and (c) an unstimulated culture. Diagnostic success rates achieved by
      these three methods were as follows: 43 per cent (95 per cent CI: 23-64) (GM
      CSF), 30 per cent (95 per cent CI: 12-49) (PHA) and 9 per cent (unstimulated).
      These three regimes were also assayed in three-day cultures giving 100 per cent
      diagnostic success rate for the PHA and GM-CSF, and 62 per cent (95 per cent CI:
      41-83) for the unstimulated. A moderate correlation was found between the initial
      concentration of cultured erythroblasts and the metaphase count in one-day GM-CSF
      stimulated (r=0.43, p=0.01) and unstimulated (r=0.35, p=0.05) cultures,
      suggesting that erythroblasts may be in part responsible for the mitotic index
      observed in these two regime cultures. In conclusion, our experience suggests
      that immature cells in fetal blood may be successfully cultured for diagnostic
      purposes.

PMID- 10073901
TI  - Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the
      fibroblast growth factor receptor 3 gene and a proposed correction of previously
      published PCR results.
AB  - Thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal
      skeletal dysplasia. Recently. mutations in the fibroblast growth factor receptor
      3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II
      (TDII), have been identified. This discovery has now made it possible to make a
      definite diagnosis of TD by molecular methods. To date, prenatal diagnosis of TD
      has been accomplished by ultrasonography in the second trimester. However, it is
      not always possible to distinguish TD fetuses it utero from the other
      osteochondrodysplasias by ultrasonography or radiography. We report on the
      prenatal diagnosis of a TD fetus, showing severe shortness of limbs and
      polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic DNA
      was isolated from the amniotic fluid and then subjected to PCR amplification. The
      common TDI mutation, C-->T transition at nucleotide 742 in the FGFR3 gene, was
      identified using restriction enzyme analysis. This information was critical in
      obstetric management decisions later in pregnancy. However, although the mutation
      responsible for TDI was detected previously, we noticed some inconsistencies in
      the published PCR results and have proposed a correction.

PMID- 10073902
TI  - Prenatal interphase detection by FISH of a sex chromosome mosaicism when
      cytogenetics reports a pseudomosaicism.
AB  - We report the detection of a sex chromosome mosaicism (XY/XXY/XYY) by prenatal
      interphase FISH (fluorescence in situ hybridization) originally identified as a
      pseudomosaicism involving 47,XXY cells present in a routine 46,XY cytogenetic
      analysis. After a fetal demise, interphase FISH identified the sex chromosome
      mosaicism in all tissues examined while cytogenetic analysis revealed only a
      normal male cell line. After prolonged exposure to colcemid, cytogenetic analysis
      identified the 47,XXY cell line. This confirmed the presence of the mosaicism and
      suggested that the abnormal cell line(s) may have been growth disadvantaged. This
      in turn may have accounted for the intra-uterine fetal demise. The identification
      by FISH and the role of growth-disadvantaged cell lines may provide a unique
      insight into chromosomally normal fetal demises.

PMID- 10073903
TI  - Trisomy 15 CPM: probable origins, pregnancy outcome and risk of fetal UPD:
      European Collaborative Research on Mosaicism in CVS (EUCROMIC).
AB  - Different origins for trisomy 15 mosaicism confined to the placenta have been
      suggested. We have analysed the data on trisomy 15 mosaicism in EUCROMIC. Trisomy
      15 mosaicism or non-mosaic feto-placental discrepancy on CVS was registered in
      0.027 per cent of samples karyotyped (34/126 465): 28/34 had confined placental
      mosaicism (CPM), 1/34 was probably true fetal mosaicism and 5/34 could not be
      classified. In 17 of the 28 pregnancies with CPM, cytogenetic information existed
      on both cytotrophoblast lineage (direct CVS preparation or short-term incubation)
      and extra-embryonic mesoderm, EEM (villus culture): CPM was of type I (restricted
      to the cytotrophoblast) in 5/17 (29 per cent); type II (restricted to the EEM) in
      4/17 (24 per cent) and type III (both cytotrophoblast and EEM) in 8/17 (47 per
      cent). Testing for uniparental disomy (UPD) for chromosome 15 in the fetus or
      child was done in nine cases, showing upd(15)mat in 1/9, and biparental
      inheritance in 8/9. Upd(15)mat, clinically diagnosed due to Prader Willi
      syndrome, but without DNA analysis, was registered in one additional liveborn
      child. Analysis of these 17 cases, in conjunction with 10 similar reports in the
      literature also having cytogenetic data from both cell lineages, indicates two
      categories of trisomy 15 CPM. One has a high proportion of trisomic cells, often
      with a type III distribution, and an observed high risk of UPD and adverse
      pregnancy outcome. The second has lower proportions of trisomic cells, primarily
      of type I or II distribution, and a lower empirical risk of UPD or pregnancy
      loss. Based on this cytogenetic analysis, supported by the available DNA data, we
      suggest that, in contrast to trisomy 16 CPM, the trisomic cell line originates
      from a meiotic error in only about 50 per cent of cases of trisomy 15 CPM, the
      rest being the result of post-zygotic, mitotic non-disjunction. Despite this, we
      recommend amniocentesis following the finding of a mosaic or non-mosaic trisomy
      15 by CVS, in order to exclude both UPD and potential true fetal mosaicism.

PMID- 10073904
TI  - Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation
      analysis.
AB  - We have performed prenatal diagnosis for Wiskott Aldrich syndrome (WAS) in two
      unrelated families by direct gene analysis. Using a combined non-radioactive
      analysis of single-strand conformational polymorphism (SSCP) and heteroduplex
      formation (HD), followed by automated sequencing, we studied DNA from chorionic
      villus sampling (CVS), allowing the diagnosis of one affected and one healthy
      male at the 12th week of gestation.

PMID- 10073905
TI  - Prenatal genotyping of the Duffy blood group system by allele-specific polymerase
      chain reaction.
AB  - Maternal allo-immunization to antigens of the Duffy blood group system can result
      in haemolytic disease of the newborn (HDN), therefore, the application of allele
      specific polymerase chain reaction (ASPCR) for prenatal genotyping of the Duffy
      antigen system to identify pregnancies at risk for HDN was evaluated.
      Oligonucleotide primers were designed for ASPCR of FYA, FYB and nullFY alleles. A
      validation study was performed using DNA isolated from 94 serotyped whole blood
      samples and 8 amniocentesis samples. A concordance rate of 100 per cent was
      observed between serotyping and ASPCR detection of the FYA, FYB and nullFY
      alleles. This assay is particularly useful for rapid genotyping of fetal amniotic
      cells to identify pregnancies at risk for HDN due to maternal fetal
      incompatibilities within the Duffy blood group system.

PMID- 10073906
TI  - The prenatal diagnosis of X-linked adrenoleukodystrophy.

PMID- 10073907
TI  - Prenatal detection of a 1p36 deletion in a fetus with multiple malformations and
      a review of the literature.
AB  - The prenatal diagnosis of a 1p36 deletion is reported. The pregnancy was
      ascertained at 24 weeks of gestation because of the discovery of multiple
      malformations at ultrasound including hypotelorism, moderate cerebral ventricular
      dilatation and Ebstein anomaly with secondary cardiac failure. Following
      cytogenetic studies and counselling, the pregnancy was terminated and a fetal
      autopsy performed. The phenotype of this antenatally-diagnosed case is compared
      with the clinical features of 44 previously reported cases with an identical
      deletion of the short arm of chromosome 1p36.

PMID- 10073908
TI  - Prenatal diagnosis of thrombocytopenia absent radius (TAR) syndrome and vaginal
      delivery.
AB  - A fetus with bilateral radial aplasia was identified on routine ultrasound. The
      diagnosis of thrombocytopenia absent radius (TAR) syndrome was confirmed with
      cordocentesis. The differential diagnosis of radial aplasia and prenatal tests
      available to assist with management are discussed. Cordocentesis offered useful
      information in the management of this case for both diagnosis and in deciding the
      route of delivery. We believe our case represents the first prenatal diagnosis of
      TAR syndrome in which vaginal delivery of a liveborn infant was intentionally
      allowed. Caesarean delivery may not be necessary for all fetuses diagnosed with
      TAR syndrome.

PMID- 10073909
TI  - Molecular exclusion of haemoglobin SD disease by prenatal diagnosis.
AB  - The most common Hb D variant, Haemoglobin D (Hb D) Los Angeles is caused by a
      glutamic acid to glutamine substitution at codon 121 of the beta globin gene.
      Although asymptomatic in the heterozygous form, inheritance together with an Hb S
      allele can result in a severe disease similar to sickle-cell anaemia that is
      referred to as Hb SD disease. Prenatal diagnosis for Hb SD disease was requested
      by an at-risk couple of Irish/English descent. Prenatal diagnosis was performed
      on DNA isolated from chorionic villi at 12 weeks' gestation using dot blot and
      allele-specific oligonucleotide hybridization for the HbS mutation, and two
      independent approaches, restriction fragment analysis and ARMS (amplification
      refractory mutation system) for the detection of the Hb D Los Angeles mutation.
      The fetus was found to be heterozygous for the HbS mutation, but did not inherit
      the HbD mutation. Thus, a reliable and rapid prenatal diagnosis for the Hb SD
      disease can be achieved by molecular diagnosis.

PMID- 10073910
TI  - Genotyping of a case of tyrosinaemia type I with normal level of succinylacetone
      in amniotic fluid.
AB  - Tyrosinaemia type I is caused by a deficiency of fumarylacetoacetate hydrolase
      and mainly affects the liver. This disease is characterized by the presence of a
      high level of succinylacetone. This metabolite has been used for prenatal
      diagnosis from amniotic fluid samples. One case with a normal level of
      succinylacetone in amniotic fluid has recently been described (Grenier et al.,
      1996). Here, we report that this patient is a compound heterozygote for two known
      mutations: E364X and IVS6-1g-->t. The low level of succinylacetone cannot be
      explained by these mutations.

PMID- 10073911
TI  - Pitfalls in prenatal diagnosis of DMD due to placental mosaicism of the X
      chromosomes: prenatal and postnatal findings in a fetus with a deletion of exons
      67-71 of the dystrophin gene.
AB  - Prenatal diagnosis of Duchenne and Becker muscular dystrophy (DMD) is performed
      as a routine procedure in many laboratories. The major potential problem is an
      incorrect diagnosis that could be obtained due to contamination with maternal
      tissue. We report a case of mosaicism of the X-chromosomes confined to the
      placenta as a possible source of confusing results in prenatal diagnosis of DMD.
      To the best of our knowledge, this is the first reported case of this problem in
      a prenatal DMD diagnosis.

PMID- 10073912
TI  - Prenatal diagnosis of Smith-Lemli-Opitz syndrome in a pregnancy with low maternal
      serum oestriol and a sex-reversed fetus.
AB  - A cytogenetically normal male fetus was subsequently found to have female
      external genitalia, a cardiac malformation and mid-trimester intra-uterine growth
      retardation by ultrasound examination. The maternal serum oestriol level was low.
      The combination of low oestriol and sonographic findings suggested Smith Lemli
      Opitz syndrome (SLO), which was confirmed by a markedly increased amniotic fluid
      level of 7-dehydrocholesterol. We review the differential diagnosis of apparent
      sex reversal in a fetus and low maternal serum oestriol level. To further examine
      the specificity of low maternal oestriol level as a marker for SLO a follow-up
      study of 12141 pregnancies screened for Down syndrome using three biochemical
      markers: alpha-fetoprotein, beta-human chorionic gonadotrophin and oestriol was
      performed. 26 pregnancies had an oestriol level that was 0.25 MoM or less. SLO
      was not diagnosed clinically in any of the liveborn children ascertained through
      a low maternal oestriol level. Nine of the pregnancies ended in spontaneous
      miscarriage. Although the frequency of SLO in pregnancies with low maternal
      oestriol levels or sex-reversed fetuses is unknown, the diagnosis of SLO should,
      nevertheless, be considered in both clinical settings.

PMID- 10073913
TI  - 'Identical' twins with discordant karyotypes.
AB  - A chromosomal abnormality in one of the fetuses of a monozygotic twin pregnancy
      is a rare phenomenon. In the prenatal unit of our cytogenetics laboratory we have
      recently come across two such heterokaryotypic twin pregnancies. In both cases
      ultrasound abnormalities were detected in one fetus of each twin pair.
      Chromosomal analysis showed that one twin pregnancy was discordant for trisomy 21
      and the other for 45,X. Ultrasonographic examination suggested a monochorionic
      twin pregnancy in each case and DNA studies confirmed that both sets of twins
      were monozygotic. Both pregnancies were terminated. Biopsies taken from different
      sites of the placentas showed chromosomal mosaicism in both cases. There was no
      clear correlation between the karyotype found close to the site of the umbilical
      cord insertion in the placenta and the karyotype of the fetus. Sampling of
      amniotic fluid from both sacs is recommended in diamniotic twin pregnancies if
      one (or both) of the fetuses has ultrasound abnormalities, even if the twins are
      apparently monochorionic.

PMID- 10073914
TI  - Prenatal finding of a fetus with mosaicism for two balanced de novo chromosome
      rearrangements.
AB  - Karyotyping of a fetus with mild cerebral ventriculomegaly detected with
      ultrasound at 23 weeks revealed two apparently balanced structural rearrangements
      in mosaic form. Using conventional cytogenetics and FISH, the chromosomal
      constitution was identified as 46,XX,t(3;10)(p13;q21.1),inv(6)(p23q12)/46,XX. A
      46,XX chromosome constitution was predominantly present in the skin whereas in
      the fetal blood the cell line with two balanced chromosome rearrangements was
      selectively retained. To the best of our knowledge this is the first prenatal
      case of mosaicism for two de novo balanced structural chromosome rearrangements
      to be reported.

PMID- 10073915
TI  - Prenatal diagnosis of hepatic mesenchymal hamartoma.
AB  - A case of hepatic mesenchymal hamartoma diagnosed prenatally with ultrasound and
      confirmed histologically post-delivery is presented. Although histologically
      benign, this lesion resulted in fetal demise secondary to congestive cardiac
      failure in the third trimester. The development of non-immune hydrops in
      association with a fetal hepatic mesenchymal hamartoma is a poor prognostic sign
      for perinatal survival.

PMID- 10073916
TI  - Stability of free beta-subunit in routine practice for trisomy 21 maternal serum
      screening.

PMID- 10073917
TI  - Prenatal exclusion of UPD from cytogenetic slides: a simple method.

PMID- 10073918
TI  - Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial
      cells demonstrates neuroblast commitment and differentiation.
AB  - Neuronal microtubules have unique stability properties achieved through
      developmental regulation at the expression and posttranslational levels on
      tubulins and microtubule associated proteins. One of the most specialized
      tubulins specific for neurons is class-III beta-tubulin (also known as beta6
      tubulin). Both the upregulation and the post-translational processing of class
      III beta-tubulin are believed to be essential throughout neuronal
      differentiation. The present investigation documents the temporal and spatial
      patterns of class-III beta-tubulin expression throughout neurogenesis. For this
      study a novel polyclonal antiserum named U-beta6, specific to unphosphorylated
      class-III beta-tubulin has been developed, characterized and compared with its
      commercial homologue TuJ-1. Our experiments indicate that the two antibodies
      recognize different forms of class-III beta-tubulin both in vitro and in vivo.
      Biochemical data revealed that U-beta6 bound unphosphorylated soluble class-III
      beta-tubulin specifically, while TuJ-1 recognized both the phosphorylated and
      unphosphorylated forms of the denatured protein. In vivo U-beta6 was associated
      with neurogenesis and labelled newly committed CNS and PNS neuroblasts expressing
      neuroepithelial cytoskeletal (nestin and vimentin) and surface markers (the anti
      ganglioside supernatant, A2B5 and the polysialic acid neural adhesion molecule,
      PSA-NCAM), as well as differentiating neurons. These studies with U-beta6
      illustrate three main developmental steps in the neuronal lineage: the commitment
      of neuroepithelial cells to the lineage (U-beta6 +ve/TuJ-1-ve cells); a
      differentiation stage (U-beta6 +ve/TuJ-1 +ve cells); and, finally, neuronal
      maturation correlating with a drop in unphosphorylated class-III beta-tubulin
      immunostaining levels. These investigations also conclude that U-beta6 is an
      earlier marker than TuJ-1 for the neuronal lineage in vivo, and it is thus the
      earliest neuronal lineage marker known so far.

PMID- 10073919
TI  - Farm worker illness following exposure to carbofuran and other pesticides--Fresno
      County California, 1998.
AB  - In California, suspected pesticide-related illnesses and suspected work-related
      illnesses and injuries are reportable conditions. On July 31, 1998, the
      Occupational Health Branch of the California Department of Health Services (CDHS)
      received a report from the California Department of Pesticide Regulation (CDPR)
      of a pesticide exposure incident in Fresno County involving 34 farm workers. CDHS
      investigated this incident by reviewing medical records of the 34 workers and
      interviewing 29. The findings indicated that the workers became ill after early
      reentry into a cotton field that had been sprayed with a cholinesterase
      inhibiting carbamate pesticides

PMID- 10073920
TI  - Screening for colorectal cancer--United States, 1997.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      United States. During 1999, approximately 129,400 new cases of colorectal cancer
      will be diagnosed, and 56,600 persons will die from the disease. In 1996, the
      U.S. Preventive Services Task Force (USPSTF) recommended the use of specific
      screening tests (i.e., annual fecal-occult blood testing [FOBT] and/or periodic
      flexible sigmoidoscopy for persons aged > or =50 years) to reduce colorectal
      cancer-related mortality. In 1997, the American Cancer Society and an
      interdisciplinary task force developed guidelines that recommend one test or a
      combination of several tests for colorectal cancer screening. To estimate the
      proportion of the U.S. population that received colorectal cancer screening
      tests, CDC analyzed data from the 1997 Behavioral Risk Factor Surveillance System
      (BRFSS) on the use of a home-administered blood stool test, or FOBT, and
      sigmoidoscopy/proctoscopy. This report summarizes the results of this analysis,
      which documents low rates of use of colorectal cancer screening tests.

PMID- 10073921
TI  - Progress toward poliomyelitis eradication--Pakistan, 1994-1998.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis by
      2000, polio cases reported globally have decreased by approximately 85%. Despite
      a strong commitment to polio eradication, polio remains endemic in Pakistan. In
      1997, Pakistan reported 1147 polio cases, representing widespread poliovirus
      circulation nationally and constituting 22% of cases reported worldwide. However,
      surveillance and laboratory data from 1998 indicate that previous widespread
      poliovirus circulation was geographically localized for the first time. This
      report describes polio eradication activities in Pakistan, including the impact
      of routine and supplementary vaccination on polio incidence.

PMID- 10073922
TI  - New population standard for age-adjusting death rates.

PMID- 10073923
TI  - Storage and executive processes in the frontal lobes.
AB  - The human frontal cortex helps mediate working memory, a system that is used for
      temporary storage and manipulation of information and that is involved in many
      higher cognitive functions. Working memory includes two components: short-term
      storage (on the order of seconds) and executive processes that operate on the
      contents of storage. Recently, these two components have been investigated in
      functional neuroimaging studies. Studies of storage indicate that different
      frontal regions are activated for different kinds of information: storage for
      verbal materials activates Broca's area and left-hemisphere supplementary and
      premotor areas; storage of spatial information activates the right-hemisphere
      premotor cortex; and storage of object information activates other areas of the
      prefrontal cortex. Two of the fundamental executive processes are selective
      attention and task management. Both processes activate the anterior cingulate and
      dorsolateral prefrontal cortex.

PMID- 10073924
TI  - Illuminating single molecules in condensed matter.
AB  - Efficient collection and detection of fluorescence coupled with careful
      minimization of background from impurities and Raman scattering now enable
      routine optical microscopy and study of single molecules in complex condensed
      matter environments. This ultimate method for unraveling ensemble averages leads
      to the observation of new effects and to direct measurements of stochastic
      fluctuations. Experiments at cryogenic temperatures open new directions in
      molecular spectroscopy, quantum optics, and solid-state dynamics. Room
      temperature investigations apply several techniques (polarization microscopy,
      single-molecule imaging, emission time dependence, energy transfer, lifetime
      studies, and the like) to a growing array of biophysical problems where new
      insight may be gained from direct observations of hidden static and dynamic
      inhomogeneity.

PMID- 10073925
TI  - Fluorescence spectroscopy of single biomolecules.
AB  - Recent advances in single-molecule detection and single-molecule spectroscopy at
      room temperature by laser-induced fluorescence offer new tools for the study of
      individual macromolecules under physiological conditions. These tools relay
      conformational states, conformational dynamics, and activity of single biological
      molecules to physical observables, unmasked by ensemble averaging. Distributions
      and time trajectories of these observables can therefore be measured during a
      reaction without the impossible need to synchronize all the molecules in the
      ensemble. The progress in applying these tools to biological studies with the use
      of fluorophores that are site-specifically attached to macromolecules is
      reviewed.

PMID- 10073926
TI  - Nanoscale science of single molecules using local probes 
AB  - Experiments on individual molecules using scanning probe microscopies have
      demonstrated an exciting diversity of physical, chemical, mechanical, and
      electronic phenomena. They have permitted deeper insight into the quantum
      electronics of molecular systems and have provided unique information on their
      conformational and mechanical properties. Concomitant developments in
      experimentation and theory have allowed a diverse range of molecules to be
      studied, varying in complexity from simple diatomics to biomolecular systems. At
      the level of an individual molecule, the interplays of mechanical and
      electronical behavior and chemical properties manifest themselves in an unusually
      clear manner. In revealing the crucial role of thermal, stochastic, and quantum
      tunneling processes, they suggest that dynamics is inescapable and may play a
      decisive role in the evolution of nanotechnology.

PMID- 10073928
TI  - Mantle values of thermal conductivity and the geotherm from phonon lifetimes 
AB  - A model for thermal conductivity kappa, based on phonon lifetimes obtained from
      infrared reflectivity, replicates experimental data at ambient conditions. The
      pressure and absolute temperature dependences of transport properties are
      accurately obtained from the Gruneisen parameter gammaTh, bulk modulus KT, and
      thermal expansivity alpha: The lattice contribution kappalat equals
      kappa298(298/T)a exp[-(4gammaTh + 1/3) integral298Talpha(theta)dtheta] with a =
      0.33 for silicates (or 0.9 for MgO), and partial differential[ln(kappalat)]/
      partial differentialP = (1/3 + 4gammaTh)/KT. The smaller, pressure-independent
      radiative contribution kapparad equals 0.0175 - 0.0001037T + (2.245T2/10(7)) -
      (3.407T3/10(11)), in units of watts per meter-kelvin, if Fe2+ is present. The
      resulting lithospheric geotherm is steep. Consequently, the mantle geotherm is
      hot if the low-velocity zone is anhydrous, but cold if hydrated.

PMID- 10073927
TI  - Single-molecule biomechanics with optical methods.
AB  - Single-molecule observation and manipulation have come of age. With the advent of
      optical tweezers and other methods for probing and imaging single molecules,
      investigators have circumvented the model-dependent extrapolation from ensemble
      assays that has been the hallmark of classical biochemistry and biophysics. In
      recent years, there have been important advances in the understanding of how
      motor proteins work. The range of these technologies has also started to expand
      into areas such as DNA transcription and protein folding. Here, recent
      experiments with rotary motors, linear motors, RNA polymerase, and titin are
      described.

PMID- 10073929
TI  - A well-collimated quasi-continuous atom laser 
AB  - Extraction of sodium atoms from a trapped Bose-Einstein condensate (BEC) by a
      coherent, stimulated Raman process is demonstrated. Optical Raman pulses drive
      transitions between trapped and untrapped magnetic sublevels, giving the output
      coupled BEC fraction a well-defined momentum. The pulsed output coupling can be
      run at such a rate that the extracted atomic wave packets strongly overlap,
      forming a highly directional, quasi-continuous matter wave.

PMID- 10073930
TI  - Quantum-well states as fabry-Perot modes in a thin-film electron interferometer 
AB  - Angle-resolved photoemission from atomically uniform silver films on iron (100)
      shows quantum-well states for absolutely determined film thicknesses ranging from
      1 to approximately 100 monolayers. These states can be understood in terms of
      Fabry-Perot modes in an electron interferometer. A quantitative line shape
      analysis over the entire two orders of magnitude of thickness range yields an
      accurate measurement of the band structure, quasiparticle lifetime, electron
      reflectivity, and phase shift. Effects of confinement energy gap, reflection
      loss, and surface scattering caused by controlled roughness are demonstrated.

PMID- 10073931
TI  - Ice core records of atmospheric CO2 around the last three glacial terminations 
AB  - Air trapped in bubbles in polar ice cores constitutes an archive for the
      reconstruction of the global carbon cycle and the relation between greenhouse
      gases and climate in the past. High-resolution records from Antarctic ice cores
      show that carbon dioxide concentrations increased by 80 to 100 parts per million
      by volume 600 +/- 400 years after the warming of the last three deglaciations.
      Despite strongly decreasing temperatures, high carbon dioxide concentrations can
      be sustained for thousands of years during glaciations; the size of this phase
      lag is probably connected to the duration of the preceding warm period, which
      controls the change in land ice coverage and the buildup of the terrestrial
      biosphere.

PMID- 10073932
TI  - Present-Day deformation across the basin and range province, western united
      states 
AB  - The distribution of deformation within the Basin and Range province was
      determined from 1992, 1996, and 1998 surveys of a dense, 800-kilometer-aperture,
      Global Positioning System network. Internal deformation generally follows the
      pattern of Holocene fault distribution and is concentrated near the western
      extremity of the province, with lesser amounts focused near the eastern boundary.
      Little net deformation occurs across the central 500 kilometers of the network in
      western Utah and eastern Nevada. Concentration of deformation adjacent to the
      rigid Sierra Nevada block indicates that external plate-driving forces play an
      important role in driving deformation, modulating the extensional stress field
      generated by internal buoyancy forces that are due to lateral density gradients
      and topography near the province boundaries.

PMID- 10073933
TI  - A search for companions to nearby brown dwarfs: the binary DENIS-P J1228.2-1547 
AB  - Hubble Space Telescope imaging observations of two nearby brown dwarfs, DENIS-P
      J1228.2-1547 and Kelu 1, made with the near-infrared camera and multiobject
      spectrometer (NICMOS), show that the DENIS object is resolved into two components
      of nearly equal brightness with a projected separation of 0.275 arc second (5
      astronomical units for a distance of 18 parsecs). This binary system will be able
      to provide the first dynamical measurement of the masses of two brown dwarfs in
      only a few years. Upper limits to the mass of any unseen companion in Kelu 1
      yield a planet of 7 Jupiter masses aged 0. 5 x 10(9) years, which would have been
      detected at a separation larger than about 4 astronomical units. This example
      demonstrates that giant planets could be detected by direct imaging if they exist
      in Jupiter-like orbits around nearby young brown dwarfs.

PMID- 10073934
TI  - "Debye-Scherrer Ellipses" from 3D fullerene polymers: An anisotropic pressure
      memory signature 
AB  - High-pressure studies on fullerenes have previously shown the existence of one-
      and two-dimensional (2D) polymerized C60 structures. Synchrotron radiation
      measurements, performed on C60 samples quenched from 13 gigapascals and 820
      kelvin, yield unambiguous proof for the existence of a three-dimensional (3D)
      polymerized C60 derivative. Moreover, unusual ellipsoidal Debye-Scherrer
      diffraction patterns are observed, which shows that the giant anisotropic
      deformation induced by the nonhydrostatic compression is retained in the quenched
      samples. The multiple bonding possibilities of the highly symmetrical C60 allow
      the retention (down to ambient pressure) of the deformation, a phenomenon
      reported previously only under high pressure.

PMID- 10073935
TI  - Single-polymer dynamics in steady shear flow.
AB  - The conformational dynamics of individual, flexible polymers in steady shear flow
      were directly observed by the use of video fluorescence microscopy. The
      probability distribution for the molecular extension was determined as a function
      of shear rate, gamma;, for two different polymer relaxation times, tau. In
      contrast to the behavior in pure elongational flow, the average polymer extension
      in shear flow does not display a sharp coil-stretch transition. Large, aperiodic
      temporal fluctuations were observed, consistent with end-over-end tumbling of the
      molecule. The rate of these fluctuations (relative to the relaxation rate)
      increased as the Weissenberg number, gamma;tau, was increased.

PMID- 10073936
TI  - How strong is a covalent bond? 
AB  - The rupture force of single covalent bonds under an external load was measured
      with an atomic force microscope (AFM). Single polysaccharide molecules were
      covalently anchored between a surface and an AFM tip and then stretched until
      they became detached. By using different surface chemistries for the attachment,
      it was found that the silicon-carbon bond ruptured at 2.0 +/- 0.3 nanonewtons,
      whereas the sulfur-gold anchor ruptured at 1.4 +/- 0.3 nanonewtons at force
      loading rates of 10 nanonewtons per second. Bond rupture probability calculations
      that were based on density functional theory corroborate the measured values.

PMID- 10073937
TI  - Adaptation of bulk constitutive equations to insoluble monolayer collapse at the
      air-water interface.
AB  - A constitutive equation based on stress-strain models of bulk solids was adapted
      to relate the surface pressure, compression rate, and temperature of an insoluble
      monolayer of monodendrons during collapse at the air-water interface. A power law
      relation between compression rate and surface pressure and an Arrhenius
      temperature dependence of the steady-state creep rate were observed in data from
      compression rate and creep experiments in the collapse region. These relations
      were combined into a single constitutive equation to calculate the temperature
      dependence of the collapse pressure with a maximum error of 5 percent for
      temperatures ranging from 10 degrees to 25 degrees C.

PMID- 10073938
TI  - Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal
      microtubule organizing centers.
AB  - The product of the abnormal spindle (asp) gene was found to be an asymmetrically
      localized component of the centrosome during mitosis, required to focus the poles
      of the mitotic spindle in vivo. Removing Asp protein function from Drosophila
      melanogaster embryo extracts, either by mutation or immunodepletion, resulted in
      loss of their ability to restore microtubule-organizing center activity to salt
      stripped centrosome preparations. This was corrected by addition of purified Asp
      protein. Thus, Asp appears to hold together the microtubule-nucleating gamma
      tubulin ring complexes that organize the mitotic centrosome.

PMID- 10073939
TI  - Role of Pitx1 upstream of Tbx4 in specification of hindlimb identity.
AB  - In spite of recent breakthroughs in understanding limb patterning, the genetic
      factors determining the differences between the forelimb and the hindlimb have
      not been understood. The genes Pitx1 and Tbx4 encode transcription factors that
      are expressed throughout the developing hindlimb but not forelimb buds.
      Misexpression of Pitx1 in the chick wing bud induced distal expression of Tbx4,
      as well as HoxC10 and HoxC11, which are normally restricted to hindlimb
      expression domains. Wing buds in which Pitx1 was misexpressed developed into
      limbs with some morphological characteristics of hindlimbs: the flexure was
      altered to that normally observed in legs, the digits were more toe-like in their
      relative size and shape, and the muscle pattern was transformed to that of a leg.

PMID- 10073940
TI  - Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of
      axin.
AB  - Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling
      increases the amount of beta-catenin/Armadillo, which in turn activates gene
      transcription. Here the Drosophila protein D-Axin was shown to interact with
      Armadillo and D-APC. Mutation of d-axin resulted in the accumulation of
      cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less.
      Ectopic expression of d-axin inhibited Wingless signaling. Hence, D-Axin
      negatively regulates Wingless signaling by down-regulating the level of
      Armadillo. These results establish the importance of the Axin family of proteins
      in Wnt/Wingless signaling in Drosophila.

PMID- 10073941
TI  - Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila.
AB  - Segregation Distorter (SD) in Drosophila melanogaster is a naturally occurring
      meiotic drive system in which the SD chromosome is transmitted from SD/SD+ males
      in vast excess over its homolog owing to the induced dysfunction of SD+-bearing
      spermatids. The Sd locus is the key distorting gene responsible for this
      phenotype. A genomic fragment from the Sd region conferred full distorting
      activity when introduced into the appropriate genetic background by germline
      transformation. The only functional product encoded by this fragment is a
      truncated version of the RanGAP nuclear transport protein. These results
      demonstrate that this mutant RanGAP is the functional Sd product.

PMID- 10073942
TI  - Linear differentiation of cytotoxic effectors into memory T lymphocytes.
AB  - A central question in immunology is the origin of long-lived T cell memory that
      confers protection against recurrent infection. The differentiation of naive T
      cell receptor transgenic CD8+ cells into effector cytotoxic T lymphocytes (CTLs)
      and memory CD8+ cells was studied. Memory CD8+ cells that were generated after
      strong antigenic stimulation were the progeny of cytotoxic effectors and retained
      antigen-specific cytolytic activity 10 weeks after adoptive transfer to antigen
      free recipient mice. Thus, potential vaccines based on CTL memory will require
      the differentiation of naive cells into post-effector memory T cells.

PMID- 10073943
TI  - HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage.
AB  - A selective advantage against infectious disease associated with increased
      heterozygosity at the human major histocompatibility complex [human leukocyte
      antigen (HLA) class I and class II] is believed to play a major role in
      maintaining the extraordinary allelic diversity of these genes. Maximum HLA
      heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency
      syndrome (AIDS) onset among patients infected with human immunodeficiency virus
      type 1 (HIV-1), whereas individuals who were homozygous for one or more loci
      progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were
      consistently associated with rapid development of AIDS-defining conditions in
      Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian
      patients who avoided AIDS for ten or more years can be attributed to their being
      fully heterozygous at HLA class I loci, to their lacking the AIDS-associated
      alleles B*35 and Cw*04, or to both.

PMID- 10073944
TI  - Motor cortical encoding of serial order in a context-recall task.
AB  - The neural encoding of serial order was studied in the motor cortex of monkeys
      performing a context-recall memory scanning task. Up to five visual stimuli were
      presented successively on a circle (list presentation phase), and then one of
      them (test stimulus) changed color; the monkeys had to make a single motor
      response toward the stimulus that immediately followed the test stimulus in the
      list. Correct performance in this task depends on memorization of the serial
      order of the stimuli during their presentation. It was found that changes in
      neural activity during the list presentation phase reflected the serial order of
      the stimuli; the effect on cell activity of the serial order of stimuli during
      their presentation was at least as strong as the effect of motor direction on
      cell activity during the execution of the motor response. This establishes the
      serial order of stimuli in a motor task as an important determinant of motor
      cortical activity during stimulus presentation and in the absence of changes in
      peripheral motor events, in contrast to the commonly held view of the motor
      cortex as just an "upper motor neuron."

PMID- 10073946
TI  - Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1,
      ApoC2, and ApoC3.

PMID- 10073945
TI  - Analysis of macrophage scavenger receptor (SR-A) expression in human aortic
      atherosclerotic lesions.
AB  - The class A scavenger receptors (SR-As) are trimeric, integral membrane
      glycoproteins that exhibit unusually broad ligand-binding properties. A number of
      studies have suggested that these receptors may play an important role in host
      defense and in many macrophage-associated pathological processes, including
      atherosclerosis and Alzheimer's disease. The study of the expression and function
      of these receptors in human disease has been hampered by the lack of suitable
      antibodies recognizing human SR-A. This has generated questions regarding the
      nature of receptors responsible for scavenger receptor activity detected in a
      variety of cell types, including monocytes, macrophages, smooth muscle cells, and
      endothelial cells. To address these questions, we have produced high-titer
      antisera recognizing human SR-A by using mice deficient for SR-A (SR-A -/-). We
      show that SR-A -/- mice produce a significantly higher-titer immune response than
      do wild-type (SR-A +/+) littermates, with antisera of the former having a broad
      species reactivity and recognizing SR-A from humans, mice, and rabbits. The
      antisera recognize both type I and II SR-A in a wide range of immunological
      techniques. Using these antisera we show that the expression of SR-A protein is
      induced during monocyte to macrophage differentiation and that SR-A mediates 80%
      of the uptake of acetylated low density lipoprotein by human monocyte-derived
      macrophages. We also establish that human SR-A is expressed by tissue macrophages
      in liver and lung and by macrophage-derived foam cells within aortic
      atherosclerotic lesions, with little detectable expression by smooth muscle cells
      or aortic endothelium.

PMID- 10073947
TI  - Socioeconomic status and determinants of hemostatic function in healthy women.
AB  - Hemostatic factors are reported to be associated with coronary heart disease
      (CHD). Socioeconomic status (SES) is 1 of the determinants of the hemostatic
      profile, but the factors underlying this association are not well known. Our aim
      was to examine determinants of the socioeconomic differences in hemostatic
      profile. Between 1991 and 1994, we studied 300 healthy women, aged 30 to 65
      years, who were representative of women living in the greater Stockholm area.
      Fibrinogen, factor VII mass concentration (FVII:Ag), activated factor VII
      (FVIIa), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI
      1) were measured. Educational attainment was used as a measure of SES. Low
      educational level and an unfavorable hemostatic profile were both associated with
      older age, unhealthful life style, psychosocial stress, atherogenic biochemical
      factors, and hypertension. Levels of hemostatic factors increased with lower
      educational attainment. Independently of age, the differences between the lowest
      (mandatory) and highest (college/university) education in FVII:Ag levels were 41
      microg/L (95% confidence interval [CI], 15 to 66 microg/L, P=0.001), 0.26 g/L
      (95% CI, 0.10 to 0.42 g/L, P=0.001) in fibrinogen levels, and 0.11 U/mL (95% CI,
      0.09 to 0.12 U/mL, P=0.03) in levels of vWF. The corresponding differences in
      FVIIa and PAI-1 were not statistically significant. With further adjustment for
      menopausal status, family history of CHD, marital status, psychosocial stress,
      lifestyle patterns, biochemical factors, and hypertension, statistically
      significant differences between mandatory and college/university education were
      observed in FVII:Ag (difference=34 microg/L; 95% CI, 2 to 65 microg/L, P=0.05)
      but not in fibrinogen (difference=0.03 g/L; 95% CI, -0.13 to 0.19 g/L, P=0.92) or
      in vWF (difference=0.06 U/mL; 95% CI, -0.10 to 0.22 U/mL, P=0.45). An educational
      gradient was most consistent and statistically significant for FVII:Ag,
      fibrinogen, and vWF. Age, psychosocial stress, unhealthful life style,
      atherogenic biochemical factors, and hypertension mediated the association of low
      educational level with elevated levels of fibrinogen and vWF. Psychosocial stress
      and unhealthful life style were the most important contributing factors. There
      was an independent association between education and FVII:Ag, which could not be
      explained by any of these factors.

PMID- 10073948
TI  - Fibrinolytic activation markers predict myocardial infarction in the elderly. The
      Cardiovascular Health Study.
AB  - Coagulation factor levels predict arterial thrombosis in epidemiological studies,
      but studies of older persons are needed. We studied 3 plasma antigenic markers of
      fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D
      dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial
      thrombosis in healthy elderly persons over age 65. The study was a nested case
      control study in the Cardiovascular Health Study cohort of 5201 men and women
      >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146
      participants without baseline clinical vascular disease who developed myocardial
      infarction, angina, or coronary death during a follow-up of 2.4 years. Controls
      remained free of cardiovascular events and were matched 1:1 to cases with respect
      to sex, duration of follow-up, and baseline subclinical vascular disease status.
      With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an
      independent increased risk of myocardial infarction or coronary death, but not of
      angina. The relative risk for D-dimer above versus below the median value (>/=120
      microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the
      median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive
      protein and fibrinogen concentrations. There were no differences in risk by sex
      or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1,
      predicted future myocardial infarction in men and women over age 65.
      Relationships were independent of other risk factors, including inflammation
      markers. Results indicate a major role for these markers in identifying a high
      risk of arterial disease in this age group.

PMID- 10073949
TI  - Relationship of plasmin generation to cardiovascular disease risk factors in
      elderly men and women.
AB  - Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and
      fibrinolytic balance. We recently observed that elevated levels of PAP predict
      acute myocardial infarction in the elderly, yet little is known about the
      correlates of PAP. We measured PAP in 800 elderly subjects who were free of
      clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health
      Study and the Honolulu Heart Program. Median PAP levels did not differ between
      the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart
      Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts.
      In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor
      VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and
      inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37).
      PAP was associated with increased atherosclerosis as measured by the ankle-arm
      index (AAI) (P for trend, </=0.001). PAP was negatively related to factors
      associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=
      0.26; body mass index, r=-0.26), possibly reflecting an association with
      plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have
      sufficient power to detect a significant interaction, PAP and AAI appeared to be
      more weakly associated in subjects with more manifestations of the IRS: PAP
      appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic
      disorders (P</=0.001; slope estimate, -0.14) compared with the subgroup with 2 or
      more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non
      insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP
      reflects reactive fibrinolysis and is associated with subclinical
      atherosclerosis, this relationship may be weaker in populations with
      characteristics of the IRS, possibly reflecting the inhibitory effects of
      plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence
      of subclinical disease in subjects with hyperinsulinemia or glucose intolerance
      is consistent with the premise that depressed plasmin generation may enhance the
      progression of atherosclerosis in these people.

PMID- 10073950
TI  - Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock
      protein-65.
AB  - Recent data suggest that the immune system is involved in atherogenesis. Thus,
      interest has been raised as to the possible antigens that could serve as the
      initiators of the immune reaction. In the current work, we studied the effects of
      immunization with recombinant heat shock protein-65 (HSP-65) and HSP-65-rich
      Mycobacterium tuberculosis (MT) on early atherogenesis in C57BL/6J mice fed
      either a normal chow diet or a high-cholesterol diet (HCD). A rapid, cellular
      immune response to HSP-65 was evident in mice immunized with HSP-65 or with MT
      but not in the animals immunized with phosphate-buffered saline (PBS) alone.
      Early atherosclerosis was significantly enhanced in HCD-fed mice immunized with
      HSP-65 (n=10; mean aortic lesion size, 45 417+/-9258 microm2) or MT (n=15; 66
      350+/-6850 microm2) compared with PBS-injected (n=10; 10 028+/-3599 microm2) or
      nonimmunized (n=10; 9500+/-2120 microm2) mice. No fatty streak lesions were
      observed in mice fed a chow diet regardless of the immunization protocol applied.
      Immunohistochemical analysis of atherosclerotic lesions from the HSP-65- and MT
      immunized mice revealed infiltration of CD4 lymphocytes compared with the
      relatively lymphocyte-poor lesions in the PBS-treated or nonimmunized mice.
      Direct immunofluorescence analysis of lesions from HSP-65- and MT-immunized mice
      fed an HCD exhibited extensive deposits of immunoglobulins compared with the
      fatty streaks in the other study groups, consistent with the larger and more
      advanced lesions found in the former 2 groups. This model, which supports the
      involvement of HSP-65 in atherogenesis, furnishes a valuable tool to study the
      role of the immune system in atherogenesis.

PMID- 10073951
TI  - Single and combined prothrombotic factors in patients with idiopathic venous
      thromboembolism: prevalence and risk assessment.
AB  - The inherited thrombophilias--deficiencies of protein C, protein S, and
      antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor
      II G20210A predispose patients toward venous thromboembolism (VTE). The aim of
      this study was to determine the prevalence of single and combined prothrombotic
      factors in patients with idiopathic VTE and to estimate the associated risks. The
      study group consisted of 162 patients referred for work-up of thrombophilia after
      documented VTE. The controls were 336 consecutively admitted patients. In all
      subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate
      reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and
      restriction enzymes. Activities of antithrombin III and protein C, free protein S
      antigen, and lupus anticoagulant were determined in a subset of 109 patients who
      were not receiving oral anticoagulants. The prevalences of heterozygotes and
      homozygotes for factor V G1691A and factor II G20210A among patients and controls
      were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The
      prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls,
      14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A,
      and homozygous MTHFR C677T were found to be independent risk factors for VTE,
      with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms
      were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%).
      Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval
      [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II
      polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms,
      and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109
      patients in whom a complete thrombophilic work-up was performed, 74% had at least
      1 underlying defect. These data indicate that in most patients referred for
      evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic
      predispositions were discernible. The presence of >1 of the prothrombotic
      polymorphisms was associated with a substantial risk of VTE.

PMID- 10073952
TI  - Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion
      to collagen.
AB  - Gangliosides, sialic acid-containing glycosphingolipids, accumulate in
      atherosclerotic vessels. Their role in the pathogenesis of atherosclerosis is
      unknown. Gangliosides isolated from tumor cells promote collagen-stimulated
      platelet aggregation and ATP secretion and enhance platelet adhesion to
      immobilized collagen. These activities are all mediated by ganglioside effects on
      the platelet integrin collagen receptor alpha2beta1. Therefore, we hypothesized
      that gangliosides isolated from atherosclerotic plaques would enhance platelet
      adhesion to immobilized collagen, a major component of the subendothelial matrix
      of blood vessels. Furthermore, we questioned whether this effect of
      atherosclerotic gangliosides might play a role in the pathogenesis of
      atherosclerosis. To test this hypothesis, we isolated the gangliosides from
      postmortem aortas of patients with extensive atherosclerotic disease and examined
      their effects on platelet adhesion. Samples of aortic tissue taken from areas
      involved with atherosclerotic plaque demonstrated accumulation of gangliosides
      (64.9+/-6.5 nmol/g wet weight) compared with gangliosides isolated from control
      normal aortic tissue taken from children who died of noncardiac causes (NAGs;
      21.1+/-6.4 nmol/g wet weight). Interestingly, samples of tissue taken from
      diseased aortas but from areas not involved with gross plaque formation also
      demonstrated ganglioside accumulation (47.6+/-12.8 nmol/g wet weight). Next, the
      activity of each of these gangliosides on platelet adhesion to immobilized type I
      collagen was studied. Atherosclerotic aortic gangliosides (AAGs) as well as those
      isolated from grossly unaffected areas of the same aorta (UAGs) both increased
      platelet adhesion compared with control NAGs (OD570, 0. 37+/-0.11 and 0.29+/-0.14
      versus 0.16+/-0.07, respectively; P<0.01 and P<0.05, respectively). These OD570
      values corresponded to 9x10(5), 8x10(4), and 6x10(3) platelets per well after
      preincubation with 5 micromol/L AAG, UAG, and NAG, respectively. Increased
      adhesion was observed after preincubation with as little as 0.5 micromol/L AAG,
      and maximal adhesion was seen at 2.5 micromol/L, with a plateau extending to the
      highest concentration tested, 10 micromol/L. The effect of AAGs on platelet
      adhesion to collagen was abrogated by incubation of treated platelets with F-17
      anti-alpha2 monoclonal antibody (OD570, 0.13+/-0.02). Finally, the effects of the
      major individual gangliosides isolated from atherosclerotic tissues, GM3 and GD3,
      were tested. GM3 increased adhesion to collagen (OD570, 0.415+/-0.06) as did GD3
      (0.31+/-0.08). Similar to that of AAGs, the effect of both molecules was blocked
      by F-17 (0. 09+/-0.04 and 0.13+/-0.06, respectively). These experiments
      demonstrate that accumulated atherosclerotic gangliosides promote platelet
      adhesion to collagen, the major component of the subendothelial matrix.
      Furthermore, this activity is mediated by an effect of the gangliosides on the
      collagen-binding integrin alpha2beta1. This activity may provide a mechanism for
      the development of platelet thrombi at sites where atherosclerotic gangliosides
      accumulate and help to explain the role of platelets in the process of
      atherosclerotic disease progression.

PMID- 10073953
TI  - ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE
      deficient mice transplanted with ApoE-expressing macrophages.
AB  - Along with apolipoprotein (apo) E, which promotes cholesterol efflux from foam
      cells, apoA1-containing high density lipoprotein (HDL) is thought to facilitate
      the transport of cholesterol from lesions. This role for apoA1 was tested in vivo
      by lethally irradiating apoE-deficient and apoE- plus apoA1-deficient mice and
      reconstituting them with bone marrow cells isolated from wild-type (WT) mice.
      ApoE, but not apoA1, was synthesized by the transplanted bone marrow-derived
      cells. Therefore, this transplantation procedure generated apoE-deficient animals
      with atherosclerotic lesions that contained both apoE and apoA1 (E/A1 mice) and
      apoE-deficient animals with lesions that contained apoE but no apoA1 (E/A1o
      mice). As shown previously, the transplanted WT macrophage-derived apoE
      dramatically lowered the plasma hypercholesterolemia in both groups. On feeding
      with an atherogenic diet after transplantation, plasma cholesterol levels were
      raised in both groups of mice, but the levels in the E/A1 mice at 20 weeks were 2
      to 3-fold higher than in E/A1o mice. Immunohistochemical staining verified that
      apoE was abundant in lesions of both groups, whereas apoA1 was detected in the
      lesions of E/A1 mice only. Despite a 2- to 3-fold lower total plasma cholesterol
      in the E/A1o mice, the free cholesterol recovered from isolated aortas was
      approximately 60% higher and the mean lesion area in serial sections of the
      aortic valves 45% larger. Therefore, apoA1 reduces free cholesterol accumulation
      in vivo in atherosclerotic lesions.

PMID- 10073954
TI  - Cooperation between VEGF and TNF-alpha is necessary for exposure of active tissue
      factor on the surface of human endothelial cells.
AB  - This study was undertaken to characterize tissue factor (TF) induction,
      localization, and functional activity in cultured human umbilical vein
      endothelial cells (HUVECs) exposed to recombinant vascular endothelial growth
      factor (rVEGF) and recombinant tumor necrosis factor-alpha (rTNF-alpha). rVEGF (1
      nmol/L) and rTNF-alpha (500 U/mL) synergistically increased TF mRNA, protein, and
      total activity, as measured in cell lysates. To examine surface TF expression,
      living cells were treated with antibody to TF and examined microscopically.
      Almost no staining was seen in control cells or cells treated with a single
      agent. In contrast, cells treated with both agonists showed intense membrane
      staining with surface patches, appearing as buds by confocal microscopy. To
      determine surface TF activity, studies were performed using a parallel-plate flow
      chamber, which allows detection of factor Xa generation on living cells. rVEGF
      and rTNF-alpha induced little surface TF activity (0.032+/-0.008 and 0.014+/
      0.008 fmol/cm2, respectively). In combination, they significantly increased TF
      expression on the cell surface (0.429+/-0.094 fmol/cm2, P<0.05). These data
      indicate that the synergistic effect of rVEGF and rTNF-alpha is necessary to
      generate functional TF on the surface of endothelial cells. The requirement for
      multiple agonists to expose active TF may serve to protect endothelial cells from
      acting as a procoagulant surface, even under conditions of cell perturbation.

PMID- 10073955
TI  - Ankle-arm index as a predictor of cardiovascular disease and mortality in the
      Cardiovascular Health Study. The Cardiovascular Health Study Group.
AB  - Peripheral arterial disease (PAD) in the legs, measured noninvasively by the
      ankle-arm index (AAI) is associated with clinically manifest cardiovascular
      disease (CVD) and its risk factors. To determine risk of total mortality,
      coronary heart disease, or stroke mortality and incident versus recurrent CVD
      associated with a low AAI, we examined the relationship of the AAI to subsequent
      CVD events in 5888 older adults with and without CVD. The AAI was measured in
      5888 participants >/=65 years old at the baseline examination of the
      Cardiovascular Health Study. All participants had a detailed assessment of
      prevalent CVD and were contacted every 6 months for total mortality and CVD
      events (including CVD mortality, fatal and nonfatal myocardial infarction,
      congestive heart failure, angina, stroke, and hospitalized PAD). The crude
      mortality rate at 6 years was highest (32.3%) in those participants with
      prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of
      these findings (8.7%, P<0.01). Similar patterns emerged from analysis of
      recurrent CVD and incident CVD. The risk for incident congestive heart failure
      (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD
      at baseline but with a low AAI remained significantly elevated after adjustment
      for cardiovascular risk factors. Hospitalized PAD events occurred months to years
      after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in
      those at risk for incident events. A statistically significant decline in
      survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an
      independent risk factor for incident CVD, recurrent CVD, and mortality in this
      group of older adults in the Cardiovascular Health Study.

PMID- 10073956
TI  - PPARgamma activation in human endothelial cells increases plasminogen activator
      inhibitor type-1 expression: PPARgamma as a potential mediator in vascular
      disease.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) is a major physiological inhibitor
      of fibrinolysis, with its plasma levels correlating with the risk for myocardial
      infarction and venous thrombosis. The regulation of PAI-1 transcription by
      endothelial cells (ECs), a major source of PAI-1, remains incompletely
      understood. Adipocytes also produce PAI-1, suggesting possible common regulatory
      pathways between adipocytes and ECs. Peroxisomal proliferator-activated receptor
      gamma (PPAR)gamma is a ligand-activated transcription factor that regulates gene
      expression in response to various mediators such as 15-deoxy-Delta12, 14
      prostaglandin J2 (15d-PGJ2) and oxidized linoleic acid (9- and 13-HODE). The
      present study tested the hypotheses that human ECs express PPARgamma and that
      this transcriptional activator regulates PAI-1 expression in this cell type. We
      found that human ECs contain both PPARgamma mRNA and protein.
      Immunohistochemistry of human carotid arteries also revealed the presence of
      PPARgamma in ECs. Bovine ECs transfected with a PPAR response element (PPRE)
      luciferase construct responded to stimulation by the PPARgamma agonist 15d-PGJ2
      in a concentration-dependent manner, suggesting a functional PPARgamma in ECs.
      Treatment of human ECs with 15d-PGJ2, 9(S)-HODE, or 13(S)-HODE augmented PAI-1
      mRNA and protein expression, whereas multiple PPARalpha activators did not change
      PAI-1 levels. Introduction of increasing amounts of a PPARgamma expression
      construct in human fibroblasts enhanced PAI-1 secretion from these cells in
      proportion to the amount of transfected DNA. Thus, ECs express functionally
      active PPARgamma that regulates PAI-1 expression in ECs. Our results establish a
      role for PPARgamma in the regulation of EC gene expression, with important
      implications for the clinical links between obesity and atherosclerosis.

PMID- 10073957
TI  - Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro.
AB  - Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein of unknown physiological
      function. The mechanism of Lp(a) atherogenicity as well as its catabolic pathways
      are only incompletely understood at present. In this report, we show that the low
      density lipoprotein receptor (LDLR) gene family member megalin/glycoprotein (gp)
      330 is capable of binding and mediating the cellular uptake and degradation of
      Lp(a) in vitro. A mouse embryonic yolk sac cell line with native expression of
      megalin/gp330 but genetically deficient in LDLR-related protein (LRP) and a
      control cell line carrying a double knockout for both LRP and megalin/gp330 were
      compared with regard to their ability to bind, internalize, and degrade
      dioctadecyltetramethylindocarbocyanine perchlorate (DiI)-fluorescence-labeled
      Lp(a) as well as equimolar amounts of 125I-labeled Lp(a) and LDL. Uptake and
      degradation of radiolabeled Lp(a) by the megalin/gp330-expressing cells were, on
      average, 2-fold higher than that of control cells. This difference could be
      completely abolished by addition of the receptor-associated protein, an inhibitor
      of ligand binding to megalin/gp330. Mutual suppression of the uptake of 125I
      Lp(a) and of 125I-LDL by both unlabeled Lp(a) and LDL suggested that Lp(a) uptake
      is mediated at least partially by apolipoprotein B100. Binding and uptake of DiI
      Lp(a) resulted in strong signals on megalin/gp330-expressing cells versus
      background only on control cells. In addition, we show that purified
      megalin/gp330, immobilized on a sensor chip, directly binds Lp(a) in a Ca2+
      dependent manner with an affinity similar to that for LDL. We conclude that
      megalin/gp330 binds Lp(a) in vitro and is capable of mediating its cellular
      uptake and degradation.

PMID- 10073958
TI  - Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a
      large population with different states of glucose tolerance. The Insulin
      Resistance Atherosclerosis Study (IRAS).
AB  - Hyperinsulinemia is associated with the development of coronary heart disease.
      However, the underlying mechanisms are still poorly understood.
      Hypercoagulability and impaired fibrinolysis are possible candidates linking
      hyperinsulinism with atherosclerotic disease, and it has been suggested that
      proinsulin rather than insulin is the crucial pathophysiological agent. The aim
      of this study was to investigate the relationship of insulin and its precursors
      to markers of coagulation and fibrinolysis in a large triethnic population. A
      strong and independent relationship between plasminogen activator inhibitor-1
      (PAI-1) antigen and insulin and its precursors (proinsulin, 32-33 split
      proinsulin) was found consistently across varying states of glucose tolerance
      (PAI-1 versus fasting insulin [proinsulin], r=0.38 [r=0.34] in normal glucose
      tolerance; r=0.42 [r=0.43] in impaired glucose tolerance; and r=0.38 [r=0.26] in
      type 2 diabetes; all P<0.001). The relationship remained highly significant even
      after accounting for insulin sensitivity as measured by a frequently sampled
      intravenous glucose tolerance test. In a stepwise multiple regression model after
      adjusting for age, sex, ethnicity, and clinic, both insulin and its precursors
      were significantly associated with PAI-1 levels. The relationship between
      fibrinogen and insulin and its precursors was significant in the overall
      population (r=0.20 for insulin and proinsulin; each P<0.001) but showed a more
      inconsistent pattern in subgroup analysis and after adjustments for demographic
      and metabolic variables. Stepwise multiple regression analysis showed that
      proinsulin (split products) but not fasting insulin significantly contributed to
      fibrinogen levels after adjustment for age, sex, clinic, and ethnicity. Decreased
      insulin sensitivity was independently associated with higher PAI-1 and fibrinogen
      levels. In summary, we were able to demonstrate an independent relationship of 2
      crucial factors of hemostasis, fibrinogen and PAI-1, to insulin and its
      precursors. These findings may have important clinical implications in the risk
      assessment and prevention of macrovascular disease, not only in patients with
      overt diabetes but also in nondiabetic subjects who are hyperinsulinemic.

PMID- 10073959
TI  - Intravenous magnesium reduces infarct size after ischemia/reperfusion injury
      combined with a thrombogenic lesion in the left anterior descending artery.
AB  - Experimental studies have demonstrated that intravenous magnesium (Mg) can
      protect the ischemic myocardium and has an antithrombotic effect. In patients
      with myocardial infarction, the reperfusion injury is complicated by the presence
      of a thrombogenic area in the affected coronary artery that may cause repetitive
      thrombus formation and embolization. We investigated the effect of Mg on infarct
      size in a randomized study in pigs. Myocardial infarction was induced by a 50
      minute mechanical occlusion of the left anterior descending artery combined with
      an arterial injury, which stimulated a dynamic thrombus formation with emboli
      shedding on reperfusion. Magnesium sulfate (6 mmol/20 min plus 3 mmol/h) or
      saline was started at 30 minutes after coronary occlusion. Real-time ventricular
      pressure-volume loops were generated from the left ventricle by using a microtip
      pressure manometer and a conductance catheter. Platelet accumulation in the
      myocardium was evaluated by using 111In-labeled platelets. After 4 hours of
      reperfusion, the infarct size/area at risk ratio in the placebo group was 46+/
      0.06% (n=8) compared with 22+/-0.07% (n=6) in the Mg-treated animals (P=0. 03).
      Ejection fraction decreased significantly in the control group but not in the Mg
      treated animals (P=0.03). Platelet accumulation in the myocardium did not change
      significantly between the Mg- and placebo-treated animals (placebo group, 191+/
      19%; Mg group, 177+/-29%; NS). The present study demonstrates that intravenous Mg
      infusion is able to reduce infarct size by >50% and preserve the ejection
      fraction in this model where ischemia/reperfusion injury was evaluated in the
      presence of a thrombogenic area in the nutrient artery.

PMID- 10073960
TI  - Generation and characterization of human smooth muscle cell lines derived from
      atherosclerotic plaque.
AB  - The study of atherogenesis in humans has been restricted by the limited
      availability and brief in vitro life span of plaque smooth muscle cells (SMCs).
      We describe plaque SMC lines with extended life spans generated by the expression
      of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to
      extend the life span of normal adult human aortic SMCs. Resulting cell lines
      (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A
      became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA
      expression. pdSMC2 were generally diploid but with various structural and
      numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities,
      most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs
      and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16
      E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC
      morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization
      with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative
      phenotype has been hypothesized as a critical step in atherogenesis, because rat
      neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To
      confirm that our pdSMC lines likewise express this apparent plaque phenotype,
      osteopontin, platelet-derived growth factor B, and elastin mRNA levels were
      determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in
      osteopontin or platelet-derived growth factor B expression levels were observed
      in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of
      elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater
      dedifferentiation and/or additional population doublings in pdSMC1A relative to
      pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for
      matrix Gla protein, previously reported to be highly expressed by human
      neointimal SMCs in vitro. These results describe 2 novel plaque cell lines
      exhibiting various features of plaque SMC biology; pdSMC2 may represent an
      earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells
      comprising an advanced atherosclerotic lesion.

PMID- 10073961
TI  - Irradiation induces upregulation of CD31 in human endothelial cells.
AB  - Radiation-induced vascular injury is believed to be a major factor contributing
      to parenchymal atrophy, fibrosis and necrosis in normal tissue after
      radiotherapy. In this study irradiation of human umbilical vein endothelial cells
      (HUVECs) significantly increased adherence of U-937 cells in a time-dependent
      manner. Given the potential multifunctional role of CD31 in the vasculature we
      have examined the possible effects of irradiation on levels of CD31 expression in
      HUVECs. Irradiation upregulated CD31 expression on HUVECs, independently of
      initial plating density and radiation-induced changes such as cell number, cell
      cycle stage, or cell size. CD31 mRNA levels were raised in irradiated HUVECs
      relative to controls. Both CD31 mRNA and surface protein showed similar changes,
      suggesting that the increase in mRNA in irradiated HUVECs is responsible for the
      elevation in cell surface protein. A semi-quantitative study of tissue specimens
      from patients who had received radiotherapy indicated that CD31 staining in the
      blood vessels from irradiated tissues was increased compared with controls.
      Endothelial CD31 is important in the transmigration of leukocytes. We have
      demonstrated that the incorporation of monoclonal antibody to CD31 significantly
      inhibited the transmigration of human peripheral blood leukocytes through a
      monolayer of irradiated HUVECs. Taken together these data strongly suggest that
      irradiation induces a marked increase in CD31 expression on endothelial cells as
      part of a general response to irradiation. Its upregulation may play an important
      role in the development of radiation-induced normal tissue damage and thus is a
      possible target for therapeutic intervention.

PMID- 10073962
TI  - Effects of alcohol and cholesterol feeding on lipoprotein metabolism and
      cholesterol absorption in rabbits.
AB  - Alcohol fed to rabbits in a liquid formula at 30% of calories increased plasma
      cholesterol by 36% in the absence of dietary cholesterol and by 40% in the
      presence of a 0.5% cholesterol diet. The increase was caused almost entirely by
      VLDL, IDL, and LDL. Cholesterol feeding decreased the fractional catabolic rate
      for VLDL and LDL apoprotein by 80% and 57%, respectively, and increased the
      production rate of VLDL and LDL apoprotein by 75% and 15%, respectively. Alcohol
      feeding had no effect on VLDL apoprotein production but increased LDL production
      rate by 55%. The efficiency of intestinal cholesterol absorption was increased by
      alcohol. In the presence of dietary cholesterol, percent cholesterol absorption
      rose from 34.4+/-2.6% to 44.9+/-2.5% and in the absence of dietary cholesterol,
      from 84.3+/-1.4% to 88.9+/-1.0%. Increased cholesterol absorption and increased
      LDL production rate may be important mechanisms for exacerbation by alcohol of
      hypercholesterolemia in the cholesterol-fed rabbit model.

PMID- 10073963
TI  - Low-density lipoprotein particle size is inversely related to plasminogen
      activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study.
AB  - High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of
      small dense low-density lipoproteins (LDL) have both been associated with
      atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro
      studies have shown a stimulatory effect of various lipoproteins on PAI-1 release
      from different cells, including endothelial cells and adipocytes. The authors
      sought to investigate the relation of PAI-1 to LDL particle size in a large tri
      ethnic population (n=1549) across different states of glucose tolerance. LDL size
      was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2
      site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL
      size in the overall population (r=-0.21, P<0.0001), independent of gender and
      ethnicity. However, the authors found a significant interaction with glucose
      tolerance status (P=0.035). In univariate analysis, the association between PAI-1
      and LDL size was most pronounced in subjects with normal glucose tolerance (NGT,
      r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12,
      P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic
      variables and metabolic variables known to influence PAI-1 levels (triglyceride
      and insulin sensitivity), a significant inverse relation of LDL size to PAI-1
      levels was only present in NGT (P=0. 023). In subjects with IGT or overt
      diabetes, who usually have elevated PAI-1 levels, additional factors other than
      LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated
      inverse relation of LDL size and PAI-1 levels provides one possible explanation
      for the atherogeneity of small dense LDL particles.

PMID- 10073964
TI  - Expression of interleukin-10 in advanced human atherosclerotic plaques: relation
      to inducible nitric oxide synthase expression and cell death.
AB  - Inflammation is a major feature of human atherosclerosis and is central to
      development and progression of the disease. A variety of proinflammatory
      cytokines are expressed in the atherosclerotic plaque and may modulate
      extracellular matrix remodeling, cell proliferation, and cell death. Little is
      known, however, about the expression and potential role of anti-inflammatory
      cytokines in human atherosclerosis. Interleukin-10 (IL-10) is a major anti
      inflammatory cytokine whose expression and potential effects in advanced human
      atherosclerotic plaques have not been evaluated. We studied 21 advanced human
      atherosclerotic plaques. IL-10 expression was analyzed by use of reverse
      transcription-polymerase chain reaction and immunohistochemical techniques.
      Inducible nitric oxide synthase expression was assessed by using
      immunohistochemistry, and cell death was determined by use of the TUNEL method.
      Reverse transcription-polymerase chain reaction identified IL-10 mRNA in 12 of 17
      atherosclerotic plaques. Immunohistochemical staining of serial sections and
      double staining identified immunoreactive IL-10 mainly in macrophages, as well as
      in smooth muscle cells. Consistent with its anti-inflammatory properties, high
      levels of IL-10 expression were associated with significant decrease in inducible
      nitric oxide synthase expression (P<0.0001) and cell death (P<0. 0001). Hence, IL
      10, a potent anti-inflammatory cytokine, is expressed in a substantial number of
      advanced human atherosclerotic plaques and might contribute to the modulation of
      the local inflammatory response and protect from excessive cell death in the
      plaque.

PMID- 10073965
TI  - Microalbuminuria and peripheral arterial disease are independent predictors of
      cardiovascular and all-cause mortality, especially among hypertensive subjects:
      five-year follow-up of the Hoorn Study.
AB  - Microalbuminuria (MA) is associated with increased cardiovascular and all-cause
      mortality. It has been proposed that MA reflects generalized atherosclerosis and
      may thus predict mortality. To investigate this hypothesis, we studied the
      associations between, on the one hand, MA and peripheral arterial disease (PAD),
      a generally accepted marker of generalized atherosclerosis, and, on the other
      hand, cardiovascular and all-cause mortality in an age-, sex-, and glucose
      tolerance-stratified sample (n=631) of a population-based cohort aged 50 to 75
      years followed prospectively for 5 years. At baseline, the albumin-to-creatinine
      ratio (ACR) was measured in an overnight spot urine sample; MA was defined as ACR
      >2.0 mg/mmol. PAD was defined as an ankle-brachial pressure index below 0.90
      and/or a history of a peripheral arterial bypass or amputation. After 5 years of
      follow-up, 58 subjects had died (24 of cardiovascular causes). Both MA and PAD
      were associated with a 4-fold increase in cardiovascular mortality. After
      adjusting for age, sex, diabetes mellitus, hypertension, levels of total and HDL
      cholesterol and triglyceride, body mass index, smoking habits, and preexistent
      ischemic heart disease, the relative risks (RR) (95% confidence intervals) were
      3.2 (1.3 to 8.1) for MA and 2.4 (0.9 to 6.1) for PAD. When both MA and PAD were
      included in the multivariate analysis, the RRs were 2.9 (1.1 to 7.3) for MA and
      2.0 (0.7 to 5.7) for PAD. MA and PAD were both associated with an about 2-fold
      increase in all-cause mortality. The RRs of all-cause mortality associated with
      MA and PAD were about 4 times higher among hypertensive than among normotensive
      subjects. We conclude that both MA and PAD are associated with an increased risk
      of cardiovascular mortality. MA and PAD are mutually independent risk indicators.
      The associations of MA and PAD with all-cause mortality are somewhat weaker. They
      are more pronounced in the presence of hypertension than in its absence. These
      data suggest that MA affects mortality risk through a mechanism different from
      generalized atherosclerosis.

PMID- 10073966
TI  - Overexpression of human hepatic lipase and ApoE in transgenic rabbits attenuates
      response to dietary cholesterol and alters lipoprotein subclass distributions.
AB  - The effect of the expression of human hepatic lipase (HL) or human apoE on plasma
      lipoproteins in transgenic rabbits in response to dietary cholesterol was
      compared with the response of nontransgenic control rabbits. Supplementation of a
      chow diet with 0.3% cholesterol and 3.0% soybean oil for 10 weeks resulted in
      markedly increased levels of plasma cholesterol and VLDL and IDL in control
      rabbits as expected. Expression of either HL or apoE reduced plasma cholesterol
      response by 75% and 60%, respectively. The HL transgenic rabbits had substantial
      reductions in medium and small VLDL and IDL fractions but not in larger VLDL. LDL
      levels were also reduced, with a shift from larger, more buoyant to smaller,
      denser particles. In contrast, apoE transgenic rabbits had a marked reduction in
      the levels of large VLDLs, with a selective accumulation of IDLs and large
      buoyant LDLs. Combined expression of apoE and HL led to dramatic reductions of
      total cholesterol (85% versus controls) and of total VLDL+IDL+LDL (87% versus
      controls). HDL subclasses were remodeled by the expression of either transgene
      and accompanied by a decrease in HDL cholesterol compared with controls. HL
      expression reduced all subclasses except for HDL2b and HDL2a, and expression of
      apoE reduced large HDL1 and HDL2b. Extreme HDL reductions (92% versus controls)
      were observed in the combined HL+apoE transgenic rabbits. These results
      demonstrate that human HL and apoE have complementary and synergistic functions
      in plasma cholesterol and lipoprotein metabolism.

PMID- 10073967
TI  - Binding of beta-VLDL to heparan sulfate proteoglycans requires lipoprotein
      lipase, whereas ApoE only modulates binding affinity.
AB  - The binding of beta-VLDL to heparan sulfate proteoglycans (HSPG) has been
      reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the
      present study we investigated the effect of the isoform and the amount of apoE
      per particle, as well as the role of LPL on the binding of beta-VLDL to HSPG.
      Therefore, we isolated beta-VLDL from transgenic mice, expressing either
      APOE*2(Arg158-->Cys) or APOE*3-Leiden (E2-VLDL and E3Leiden-VLDL, respectively),
      as well as from apoE-deficient mice containing no apoE at all (Enull-VLDL). In
      the absence of LPL, the binding affinity and maximal binding capacity of all beta
      VLDL samples for HSPG-coated microtiter plates was very low. Addition of LPL to
      this cell-free system resulted in a 12- to 55-fold increase in the binding
      affinity and a 7- to 15-fold increase in the maximal binding capacity (Bmax). In
      the presence of LPL, the association constant (Ka) tended to increase in the
      order Enull-VLDL<E2-VLDL<E3Leiden-VLDL, whereas Bmax increased in the reverse
      order: E3Leiden-VLDL approximately E2-VLDL<Enull-VLDL. Addition of LPL resulted
      in a marked stimulation of both Ka and Bmax for binding of beta-VLDL samples to
      J774 cells similar to that found for the binding to HSPG-LPL complexes. Our
      results indicate that both Ka and Bmax for binding of beta-VLDL to HSPG are
      increased more than 1 order of magnitude on addition of LPL. In addition, for the
      binding of beta-VLDL to HSPG-LPL complexes, the presence of apoE is not a
      prerequisite, but results in an increased binding affinity, depending on the apoE
      isoform used.

PMID- 10073968
TI  - Specific interaction of oxidized low-density lipoprotein with macrophage-derived
      foam cells isolated from rabbit atherosclerotic lesions.
AB  - Interaction of oxidized LDL (OxLDL) with macrophage-derived foam cells is one of
      the key events in the development and progression of atherosclerosis. To study
      this interaction, macrophage-derived foam cells were isolated from rabbit
      atherosclerotic lesions and the expression of scavenger receptors for OxLDL was
      examined. Atherosclerosis was induced in rabbits by denudation of the large
      arteries, followed by a hypercholesteremic diet. Macrophage-derived foam cells,
      characterized by immunostaining with an RAM-11 antibody (a macrophage marker),
      contained a high content of intracellular lipid. Maximal binding of radiolabeled
      OxLDL to isolated macrophage-derived foam cells (1652+/-235 ng 125I-OxLDL/mg of
      cell protein) was 20-fold higher compared with Bmax values of monocytes. Levels
      of association of OxLDL to macrophage-derived foam cells isolated from
      atherosclerotic lesions 12 weeks after denudation were >3-fold higher compared
      with the levels expressed by macrophage-derived foam cells isolated after 6
      weeks. Association of 125I-OxLDL could be completely blocked by OxLDL, and
      partially by acetylated LDL and polyinosinic acid, indicating the presence of a
      specific binding site for OxLDL on macrophage-derived foam cells. The induction
      of scavenger receptors for OxLDL on macrophage-derived foam cells during the
      development of atherosclerosis, as described in this study, may facilitate the
      lipid accumulation in macrophage-derived foam cells, as observed in advanced
      atherosclerotic lesions.

PMID- 10073969
TI  - Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native
      and transplanted human coronary arteries and colocalizes with inducible nitric
      oxide synthase and nitrotyrosine particularly in macrophages.
AB  - Inflammation appears to have a major role in the development of atherosclerotic
      lesions affecting native and transplanted coronary arteries. The subsequent risk
      of plaque rupture and acute ischemic events correlates with the degree of
      inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase
      inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS)
      are involved in the inflammatory response via the rapid and exaggerated
      production of prostanoids and nitric oxide, both of which may have
      proatherosclerotic effects. These effects may be mediated by the formation of
      peroxynitrite in the case of nitric oxide and involve "cross talk" between the
      two enzyme systems. This study aimed to investigate native and transplant
      atherosclerosis for the presence and distribution of Cox-2 and iNOS.
      Immunocytochemical studies were performed on atherosclerotic lesions from
      patients with native (n=12) and transplant (n=5) coronary disease by using
      antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite
      production). Control tissue was obtained from unused donor hearts and at the time
      of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in
      both types of atherosclerosis. Cox-2 expression was also detected in medial
      smooth muscle cells and endothelial cells, including those of the vasa vasorum.
      Nitrotyrosine was found in the same distribution as that of iNOS and was
      colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native
      and transplant atherosclerosis, possibly allowing for interaction between the
      enzymes and suggesting an alternative mechanism for the benefits of aspirin via
      inhibition of Cox-2 activity.

PMID- 10073970
TI  - Upregulation of superoxide dismutase and nitric oxide synthase mediates the
      apoptosis-suppressive effects of shear stress on endothelial cells.
AB  - Physiological levels of laminar shear stress completely abrogate apoptosis of
      human endothelial cells in response to a variety of stimuli and might therefore
      importantly contribute to endothelial integrity. We show here that the apoptosis
      suppressive effects of shear stress are mediated by upregulation of Cu/Zn SOD and
      NO synthase. Shear stress-mediated inhibition of endothelial cell apoptosis in
      response to exogenous oxygen radicals, oxidized LDL, and tumor necrosis factor
      alpha was associated with complete inhibition of caspase-3-like activity, the
      central effector arm executing the apoptotic cell death program in endothelial
      cells. Shear stress-dependent upregulation of Cu/Zn SOD and NO synthase blocks
      activation of the caspase cascade in response to apoptosis-inducing stimuli.
      These findings establish the upregulation of Cu/Zn SOD and NO synthase by shear
      stress as a central protective cellular mechanism to preserve the integrity of
      the endothelium after proapoptotic stimulation.

PMID- 10073971
TI  - Reduced in vitro repair in endothelial cells harvested from the intercostal ostia
      of porcine thoracic aorta.
AB  - The ability of large-vessel endothelium to repair itself rapidly after injury is
      important in the maintenance of its barrier function and in limiting the
      development and progression of atherosclerosis. Because dysfunctional repair may
      be involved in the pathogenesis of some atherosclerotic plaques, including those
      at the ostia of aortic branches, linear mechanical denuding wounds were made in
      confluent monolayers of endothelial cells harvested by scraping from the flow
      divider, the upstream wall of the intercostal branch and unbranched regions in
      the thoracic aorta. The extent of wound closure was significantly lower in cells
      derived from either side of the intercostal branches, compared with cells from
      unbranched areas. The wound edge of cells harvested from the flow divider and its
      opposite wall closed by 22+/-0.084 microm and 22+/-1.3 microm, respectively,
      versus control, unbranched endothelial cells (30+/-2.2 microm) at 24 hours and by
      48 hours, 48+/-3.4 microm and 47+/-3.6 microm compared with control (61+/-3.4
      microm). Extent of wound closure in cells harvested by scraping from unbranched
      regions was comparable with collagenase-harvested endothelial cells at 24 and 48
      hours. Distribution of F-actin microfilaments, tubulin and centrosomes have been
      shown to be disrupted at the wound edge in poorly migrating cells. In our study,
      however, no differences were observed in cytoskeletal distribution between cells
      from branched, unbranched and control areas. Thus, aortic endothelial cells from
      the intercostal branch region show a reduced ability to repair wounds compared
      with cells harvested from unbranched aorta. The mechanism for this difference is
      currently unknown.

PMID- 10073972
TI  - A role for changes in platelet production in the cause of acute coronary
      syndromes.
AB  - Platelets are heterogeneous with respect to their size, density, and reactivity.
      Large platelets are more active hemostatically, and platelet volume has been
      found to be increased both in patients with unstable angina and with myocardial
      infarction. Furthermore, platelet volume is a predictor of a further ischemic
      event and death when measured after myocardial infarction. Platelets which are
      anucleate cells with no DNA are derived from their precursor, the megakaryocyte.
      Therefore, it is suggested that changes in platelet size are determined at
      thrombopoiesis in the megakaryocyte and that those changes might precede acute
      cardiac events. Understanding of the signaling system that controls platelet
      production may also further elucidate the cascade of events leading to acute
      vascular occlusion in some patients.

PMID- 10073973
TI  - Induction of monocyte binding to endothelial cells by MM-LDL: role of
      lipoxygenase metabolites.
AB  - Treatment of human aortic endothelial cells (EC) with minimally oxidized LDL (or
      minimally modified LDL, MM-LDL) produces a specific pattern of endothelial cell
      activation distinct from that produced by LPS, tumor necrosis factor-alpha, and
      interleukin-1, but similar to other agents that elevate cAMP. The current studies
      focus on the signal transduction pathways by which MM-LDL activates EC to bind
      monocytes. We now demonstrate that, in addition to an elevation of cAMP,
      lipoxygenase products are necessary for the MM-LDL response. Treatment of EC with
      inhibitors of the lipoxygenase pathway, 5,8,11, 14-eicosatetraynoic acid (ETYA)
      or cinnamyl-3, 4-dihydroxy-alpha-cyanocinnamate (CDC), blocked monocyte binding
      in MM-LDL-treated EC (MM-LDL=118+/-13%; MM-LDL+ETYA=33+/-4%; MM-LDL+CDC=23+/-4%
      increase in monocyte binding) without reducing cAMP levels. To further
      investigate the role of the lipoxygenase pathway, cellular phospholipids were
      labeled with arachidonic acid. Treatment of cells for 4 hours with 50 to 100
      microg/mL MM-LDL, but not native LDL, caused a 60% increase in arachidonate
      release into the medium and increased the intracellular formation of 12(S)-HETE
      (approximately 100% increase). There was little 15(S)-HETE present, and no
      increase in its levels was observed. We demonstrated that 12(S)-HETE reversed the
      inhibitory effect of CDC. We also observed a 70% increase in the formation of
      11,12-epoxyeicosatrienoic acid (11, 12-EET) in cells treated with MM-LDL. To
      determine the mechanism of arachidonate release induced by MM-LDL, we examined
      the effects of MM-LDL on intracellular calcium levels. Treatment of EC with both
      native LDL and MM-LDL caused a rapid release of intracellular calcium from
      internal stores. However, several pieces of evidence suggest that calcium release
      alone does not explain the increased arachidonate release in MM-LDL-treated
      cells. The present studies suggest that products of 12-lipoxygenase play an
      important role in MM-LDL action on the induction of monocyte binding to EC.

PMID- 10073974
TI  - Strong induction of members of the chitinase family of proteins in
      atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion
      macrophages.
AB  - Atherosclerosis is initiated by the infiltration of monocytes into the
      subendothelial space of the vessel wall and subsequent lipid accumulation of the
      activated macrophages. The molecular mechanisms involved in the anomalous
      behavior of macrophages in atherogenesis have only partially been disclosed.
      Chitotriosidase and human cartilage gp-39 (HC gp-39) are members of the chitinase
      family of proteins and are expressed in lipid-laden macrophages accumulated in
      various organs during Gaucher disease. In addition, as shown in this study,
      chitotriosidase and HC gp-39 can be induced with distinct kinetics in cultured
      macrophages. We investigated the expression of these chitinase-like genes in the
      human atherosclerotic vessel wall by in situ hybridizations on atherosclerotic
      specimens derived from femoral artery (4 specimens), aorta (4 specimens), iliac
      artery (3 specimens), carotid artery (4 specimens), and coronary artery (1
      specimen), as well as 5 specimens derived from apparently normal vascular tissue.
      We show for the first time that chitotriosidase and HC gp-39 expression was
      strongly upregulated in distinct subsets of macrophages in the atherosclerotic
      plaque. The expression patterns of chitotriosidase and HC gp-39 were compared and
      shown to be different from the patterns observed for the extracellular matrix
      protein osteopontin and the macrophage marker tartrate-resistant acid
      phosphatase. Our data emphasize the remarkable phenotypic variation among
      macrophages present in the atherosclerotic lesion. Furthermore, chitotriosidase
      enzyme activity was shown to be elevated up to 55-fold in extracts of
      atherosclerotic tissue. Although a function for chitotriosidase and HC gp-39 has
      not been identified, we hypothesize a role in cell migration and tissue
      remodeling during atherogenesis.

PMID- 10073975
TI  - Extent and composition of coronary lesions in relation to fat distribution in
      women younger than 50 years of age.
AB  - To ascertain the relationship between the extent and composition of coronary
      arterial lesions and the regional distribution of fat in healthy women younger
      than 50 years of age, a series of 30 forensic autopsy cases were investigated.
      Body height and weight, waist and hip circumferences, and the thickness of the
      subscapular and abdominal subcutaneous fat were measured; the body mass index
      (BMI) and waist-to-hip ratio (WHR) were calculated, and omental and mesenteric
      fat deposits were weighed. The extent of coronary lesions was measured by
      planimetry, and the thickness of the intima-media was measured by computerized
      image analysis. Intimal macrophage foam cells and smooth muscle cells were
      detected by immunohistochemistry, and macrophages were quantified. The intima
      media thickness in the left anterior descending artery, circumflex artery, and
      right coronary artery varied significantly across the tertiles of WHR when age
      and BMI were adjusted, being highest when WHR exceeded 0.87. The thickest lesions
      also contained the largest numbers of macrophage foam cells. The intima-media
      thicknesses were highest with increased amounts of intraperitoneal fat. These
      results indicate that the severity of clinically silent coronary lesions in
      younger female individuals is associated with increased WHR and increased amounts
      of intraperitoneal fat. These results emphasize the importance of WHR as a
      coronary risk indicator in younger women.

PMID- 10073976
TI  - Interaction between the G20210A mutation of the prothrombin gene and oral
      contraceptive use in deep vein thrombosis.
AB  - Single-point mutations in the gene coding for prothrombin (factor II:A20210) or
      factor V (factor V:A1691) are associated with an increased risk of venous
      thromboembolism. The use of oral contraceptives is also a strong and independent
      risk factor for the disease, and the interaction between factor V:A1691 and oral
      contraceptives greatly increases the risk. No information is available about the
      interaction between oral contraceptives and mutant prothrombin. We investigated
      148 women with a first, objectively confirmed episode of deep vein thrombosis and
      277 healthy women as controls. Fourteen patients (9.4%) were carriers of factor
      II:A20210, 24 (16.2%) of factor V:A1691, and 4 (2.7%) of both defects. Among
      controls, the prevalence was 2.5% for either factor II:A20210 or factor V:A1691,
      and there was no carrier of both the mutations. The relative risk of thrombosis
      was 6-fold for factor II:A20210 and 9-fold for factor V:A1691. The most prevalent
      circumstantial risk factor in patients and the only one observed in controls was
      oral contraceptive use, which per se conferred a 6-fold increased risk of
      thrombosis. The risk increased to 16.3 and 20.0 when women with factor II:A20210
      or factor V:A1691 who used oral contraceptives were compared with noncarriers and
      nonusers. These figures indicate a multiplicative interaction between the genetic
      risk factors and oral contraceptives. No difference in the type of oral
      contraceptives was observed between patients and controls, those of third
      generation being the most frequently used (73% and 80%). We conclude that
      carriers of the prothrombin mutation who use oral contraceptives have a markedly
      increased risk of deep vein thrombosis, much higher than the risk conferred by
      either factor alone.

PMID- 10073977
TI  - Effects of gamma-tocotrienol on ApoB synthesis, degradation, and secretion in
      HepG2 cells.
AB  - gamma-Tocotrienol (gamma-T3), a naturally occurring analog of tocopherol (vitamin
      E), has been shown to have a hypocholesterolemic effect in animals and humans.
      Unlike tocopherol, it has also been shown to reduce plasma apoB levels in
      hypercholesterolemic subjects. The aim of this study was to define the mechanism
      of action of gamma-T3 on hepatic modulation of apoB production using cultured
      HepG2 cells as the model system. HepG2 cells preincubated with gamma-T3 were
      initially shown to inhibit the rate of incorporation of [14C]acetate into
      cholesterol in a concentration- and time-dependent manner, with a maximum 86+/-3%
      inhibition at 50 micromol/L observed within 6 hours. gamma-T3, on the other hand,
      had no significant effect on the uptake of [14C]glycerol into pools of cellular
      triacylglycerol and phospholipid relative to untreated control. The rate of apoB
      synthesis and secretion was then studied by an [35S]methionine pulse-labeling
      experiment and quantified by immunoprecipitating apoB on chasing up to 3 hours.
      An average reduction of 24+/-3% in labeled apoB in the media was apparent with
      gamma-T3 despite a 60+/-2% increase in apoB synthesis. Fractionation of secreted
      apoB revealed a relatively denser lipoprotein particle, suggesting a less stable
      particle. Using a digitonin-permeabilized HepG2 cell system, the effects of gamma
      T3 on apoB translocation and degradation in the endoplasmic reticulum were
      further investigated. The generation of a specific N-terminal 70-kDa proteolytic
      fragment proved to be a sensitive measure of the rate of apoB translocation and
      degradation. The abundance of this fragment increased significantly in gamma-T3
      treated cells relative to untreated control cells (50+/-21%) after 2 hours of
      chase. In addition, the presence of gamma-T3 resulted in an average decrease of
      64+/-8% in intact apoB. Taken together, the data suggest that gamma-T3 stimulates
      apoB degradation possibly as the result of decreased apoB translocation into the
      endoplasmic reticulum lumen. It is speculated that the lack of cholesterol
      availability reduces the number of secreted apoB-containing lipoprotein particles
      by limiting translocation of apoB into the endoplasmic reticulum lumen.

PMID- 10073978
TI  - Menopausal status and distensibility of the common carotid artery.
AB  - Although several studies have shown that exogenous estrogens have beneficial
      effects on arterial characteristics, the effect of endogenous estrogen on the
      vascular system is still unknown. In this study, distensibility, an indicator of
      arterial elasticity, of the common carotid artery was compared in pre- and
      postmenopausal women. The study comprised 93 premenopausal and 93 postmenopausal
      women of similar age (range, 43 to 55 years). Women were selected from
      respondents to a mailed questionnaire about the menopause, which was sent to all
      women aged 40 to 60 years in the Dutch town of Zoetermeer (n=12 675).
      Postmenopausal women who were at least 3 years past natural menopause or whose
      menses had stopped naturally before age 48, were age-matched with premenopausal
      women with regular menses and without menopausal complaints. The selection aimed
      at maximizing the contrast in estrogen status between pre- and postmenopausal
      women of the same age. Distensibility of the carotid artery was measured
      noninvasively with B-mode ultrasound and a vessel wall movement detector system.
      Arterial distensibility is expressed as the change in arterial diameter
      (distension, DeltaD) with the cardiac cycle, adjusted for lumen diameter, pulse
      pressure, and mean arterial blood pressure. Compared with premenopausal women,
      postmenopausal women had significantly lower arterial distension (DeltaD 370.5
      microm [SE 9.5] versus 397.3 microm [SE 9.6]). These results suggest that the
      distensibility of the common carotid artery is negatively affected by natural
      menopause in presumed healthy women.

PMID- 10073979
TI  - Lipid transfer inhibitor protein defines the participation of lipoproteins in
      lipid transfer reactions: CETP has no preference for cholesteryl esters in HDL
      versus LDL.
AB  - Cholesteryl ester transfer protein (CETP) catalyzes the net transfer of
      cholesteryl ester (CE) between lipoproteins in exchange for triglyceride
      (heteroexchange). It is generally held that CETP primarily associates with HDL
      and preferentially transfers lipids from this lipoprotein fraction. This is
      illustrated in normal plasma where HDL is the primary donor of the CE transferred
      to VLDL by CETP. However, in plasma deficient in lipid transfer inhibitor protein
      (LTIP) activity, HDL and LDL are equivalent donors of CE to VLDL (Arterioscler
      Thromb Vasc Biol. 1997;17:1716-1724). Thus, we have hypothesized that the
      preferential transfer of CE from HDL in normal plasma is a consequence of LTIP
      activity and not caused by a preferential CETP-HDL interaction. We have tested
      this hypothesis in lipid mass transfer assays with partially purified CETP and
      LTIP, and isolated lipoproteins. With a physiological mixture of lipoproteins,
      the preference ratio (PR, ratio of CE mass transferred from a lipoprotein to VLDL
      versus its CE content) for HDL and LDL in the presence of CETP alone was
      approximately 1 (ie, no preference). Fourfold variations in the LDL/HDL ratio or
      in the levels of HDL in the assay did not result in significant preferential
      transfer from any lipoprotein. On addition of LTIP, the PR for HDL was increased
      up to 2-fold and that for LDL decreased in a concentration-dependent manner.
      Under all conditions where LDL and HDL levels were varied, LTIP consistently
      resulted in a PR >1 for CE transfer from HDL. Short-term experiments with
      radiolabeled lipoproteins and either partially purified or homogenous CETP
      confirmed these observations and further demonstrated that CETP has a strong
      predilection to mediate homoexchange (bidirectional transfer of the same lipid)
      rather than heteroexchange (CE for TG); LTIP had no effect on the selection of CE
      or TG by CETP or its mechanism of action. We conclude, in contrast to current
      opinion, that CETP has no preference for CE in HDL versus LDL, suggesting that
      the previously reported stable binding of CETP to HDL does not result in
      selective transfer from this lipoprotein. These data suggest that LTIP is
      responsible for the preferential transfer of CE from HDL that occurs in plasma.
      CETP and LTIP cooperatively determine the extent of CETP-mediated remodeling of
      individual lipoprotein fractions.

PMID- 10073980
TI  - Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits
      neointimal formation in rat carotid arteries after balloon injury.
AB  - Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective
      effects of vasodilation, anti-platelet aggregation, and inhibition of smooth
      muscle cell proliferation. We hypothesized that an overexpression of endogenous
      PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal
      formation in the injured artery. To test this hypothesis, we investigated in vivo
      transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid
      arteries by a nonviral lipotransfection method. Seven days after transfection, a
      significant regeneration of endothelium was observed in the arteries transfected
      with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was
      seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ)
      (percent luminal circumference lined by newly regenerated endothelium: 87. 1+/
      6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels,
      P<0.001). BrdU staining of arterial segments demonstrated a significantly lower
      incorporation in pCMV-PCS-transfected vessels (7. 5+/-0.3% positive nuclei in
      vessel cells) than in pCMV-lacZ (50. 7+/-9.6%, P<0.01). Moreover, 2 weeks after
      transfection, the PCS gene transfer resulted in a significant inhibition of
      neointimal formation (88% reduction in ratio of intima/media areas), whereas
      medial area was similar among the groups. Arterial segments transfected with pCMV
      PCS produced significantly higher levels of 6-keto-PGF1alpha, the main metabolite
      of PGI2, compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and
      2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion,
      this study demonstrated that an in vivo PCS gene transfer increased the
      production of PGI2 and markedly inhibited neointimal formation with accelerated
      reendothelialization in rat carotid arteries after balloon injury.

PMID- 10073981
TI  - The role of interleukin 12 in the development of atherosclerosis in ApoE
      deficient mice.
AB  - The cytokine profile of atherosclerotic aortas from apoE-deficient mice was
      assessed by reverse transcriptase-polymerase chain reaction. The results clearly
      showed that the expression of mRNA for IL-12p40 was evident in aortas from 3
      month-old apoE-deficient mice. The mRNA for IL-10 was detected in aorta from
      these mice at the age of 6 months, indicating that expression of IL-12 is earlier
      than that of IL-10 in these animals. Concurrent with IL-12p40, the mRNA for the T
      cell cytokine IFN-gamma, but not IL-4, was detected in aortas of mice at young
      and old ages. Both in situ hybridization and immunostaining further demonstrated
      the localization of IL-12 in macrophages of atherosclerotic lesions.
      Immunohistochemistry also demonstrated the expression of costimulatory molecules
      B7-1 and B7-2 in macrophages, suggesting that activation of T lymphocytes by
      macrophages may occur via surface antigens in lesions. When the immunoglobulin
      isotype of the antioxidized LDL antibodies in sera of apoE-deficient mice was
      determined, it revealed that both IgM and IgG were present. Furthermore, IgG2a is
      predominant and comprises approximately 50% of the antioxidized LDL IgG in sera
      from young mice (3 months), but decreased to lower levels (35%) in older mice (6
      months). Daily administration of IL-12 led to an increase in serum levels of
      antioxidized LDL antibodies and accelerated atherosclerosis in young apoE
      deficient mice compared with control mice injected with PBS alone. Taken
      together, these data suggest that IL-12 plays an active role in regulating the
      immune response during the early phase of atherosclerosis in apoE-deficient mice.

PMID- 10073982
TI  - Role of cholesterol ester mass in regulation of secretion of ApoB100 lipoprotein
      particles by hamster hepatocytes and effects of statins on that relationship.
AB  - Our understanding of the factors that regulate the secretion of apoB100
      lipoproteins remains incomplete with considerable debate as to the role, if any,
      for cholesterol ester in this process. This study examines this issue in primary
      cultures of hamster hepatocytes, a species in which both cholesterol and apoB100
      metabolism are very similar to man. Addition of oleate to medium increased the
      mass of triglyceride and cholesterol ester within the hepatocyte and also
      increased the secretion of triglycerides, cholesterol ester, and apoB100 into the
      medium. Next, the responses of hamster hepatocytes to addition of either an HMG
      CoA reductase inhibitor (lovastatin) or an acyl-CoA cholesterol acyltransferase
      inhibitor (58-035) to the medium, with or without added oleate, were determined.
      Effects of either agent were only evident in the oleate-supplemented medium in
      which cholesterol ester mass had been increased above basal. If oleate was not
      added to the medium, neither agent reduced apoB100 secretion; equally important,
      over the 24-hour incubation, neither agent, at the concentration used, produced
      any detectable change in intracellular cholesterol ester mass. However, in
      contrast to the estimates of mass, which were unchanged, under the same
      conditions radioisotopic estimates of cholesterol ester synthesis were markedly
      reduced. Any conclusion as to the relation of cholesterol ester mass to apoB100
      secretion would therefore depend on which of the 2 methods was used. Overall, the
      data indicate a close correlation between the mass of cholesterol ester within
      the hepatocyte and apoB100 secretion from it and they go far to explain previous
      apparently contradictory data as to this relation. More importantly, though,
      taken with other available data, they indicate that the primary response of the
      liver to increased delivery of lipid is increased secretion rather than decreased
      uptake. These results point, therefore, to a hierarchy of hepatic responses to
      increased flux of fatty acids and increased synthesis of cholesterol that in turn
      suggests a more dynamic model of cholesterol homeostasis in the liver than has
      been appreciated in the past.

PMID- 10073983
TI  - Lipid and apolipoprotein predictors of atherosclerosis in youth: apolipoprotein
      concentrations do not materially improve prediction of arterial lesions in PDAY
      subjects. The PDAY Research Group.
AB  - We compared serum lipid and apolipoprotein predictors of atherosclerosis in cases
      from the multicenter study, Pathobiological Determinants of Atherosclerosis in
      Youth (PDAY). The lipid measures included HDL cholesterol (HDL-C) and non-HDL-C,
      and the apolipoprotein measures included concentrations of apoA1, apoB, and
      Lp(a), and sizes of the apo(a) proteins. We tested whether the apolipoprotein
      measures predicted atherosclerotic lesions as well as the more traditional lipid
      measures. We estimated extent of lesions as fatty streaks or raised lesions
      (fibrous plaques, complicated or calcified lesions) in 3 sites: thoracic aorta,
      abdominal aorta, and right coronary artery. Neither apoA1 nor apoB measures were
      as strongly or consistently correlated with extent of lesions as the
      corresponding lipid measure (HDL-C and non-HDL-C, respectively). Beyond the basic
      model that included sex, age, race, smoking status, hypertension, and the lipid
      measures, apoA1 and apoB added only an average 1.3% increased explanatory ability
      to the model, whereas HDL-C plus non-HDL-C added an average 2.5%. The results
      suggest that the traditional lipid measures are more useful than apolipoprotein
      measures for detecting young persons at high risk of precocious atherosclerosis.
      Because of large racial differences, the two Lp(a)-related measures, Lp(a)
      concentrations and apo(a) size, were evaluated in blacks and whites separately.
      Under these circumstances, neither of the Lp(a)-related measures was strongly or
      consistently correlated with extent of lesions.

PMID- 10073984
TI  - Increased serotonin receptor density and platelet GPIIb/IIIa activation among
      smokers.
AB  - This study sought to determine whether depressive symptoms and/or platelet
      serotonin receptor (5HT2A) density are associated with increased platelet
      activation (PA) found among smokers. Flow cytometric detection of PA was used to
      study 36 smokers and 16 nonsmokers, aged 18 to 48 years. Subjects were tested at
      baseline and after either smoking 2 cigarettes (smokers) or a similar resting
      interval (nonsmokers). Assessment of PA included both platelet secretion and
      fibrinogen receptor (GPIIb/IIIa) binding. Platelet 5HT2A receptor binding and
      saturation were tested using [3H]LSD, and depressive symptoms were measured using
      the Beck Depression Inventory. Platelet 5HT2A receptor density was increased
      among smokers versus nonsmokers (82.7+/-67.7 versus 40.0+/-20.2 fmol/mg protein;
      P<0.005), and there was a dose-dependent relationship between receptor density
      and packs/d among smokers. Baseline wound-induced GPIIb/IIIa binding at 1 minute
      and GPIIb/IIIa binding in response to collagen stimulation in vitro was increased
      among smokers (P<0.05); there were no changes in PA among smokers after smoking,
      and platelet secretion was not elevated among smokers. Depressive symptoms were
      associated with 5HT2A receptor density among nonsmokers (P<0.005), but no such
      relationship was evident among smokers; PA was unrelated to 5HT2A receptor
      density in either group. The findings indicate that smoking is associated with
      increased platelet serotonin receptor density and with increased GPIIb/IIIa
      receptor binding, although these 2 factors are not related to each other or to
      depressive symptoms among smokers. Serotonergic dysfunction may be an important
      factor in the development of cardiovascular disease among smokers.

PMID- 10073985
TI  - Continuous perivascular L-arginine delivery increases total vessel area and
      reduces neointimal thickening after experimental balloon dilatation.
AB  - The aim of this study was to evaluate whether vascular remodeling and neointimal
      thickening occur after balloon dilatation of the nonatherosclerotic rabbit
      carotid artery, and whether both processes are influenced by continuous
      perivascular delivery of L-arginine or the nitric oxide synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME). In the first experiment, histological and
      morphometric evaluation of arteries was performed at different time points after
      balloon dilatation: 10 minutes (n=7), and 1 (n=7), 2 (n=9), 3 (n=20), or 10 (n=5)
      weeks. Neointimal thickening progressively contributed to luminal narrowing for
      at least 10 weeks after angioplasty. During the first 2 weeks after dilatation, a
      significant decrease of the total vessel area was measured. Ten weeks after
      dilatation, both the neointimal and total vessel area were increased without
      further changing of the luminal area. In the second experiment, endothelial
      injured rabbits were randomly assigned to receive 2 weeks of continuous local
      perivascular physiological salt solution (n=6), L-arginine (n=8), or L-NAME
      (n=7), starting immediately after balloon dilatation (ie, local drug delivery
      during the first phase of the biphasic vascular remodeling process). Perivascular
      L-arginine delivery significantly reduced the neointimal area, despite an
      increased number of neointimal Ki-67-positive smooth muscle cells. Both the
      luminal area and total vessel area were significantly increased. Serum L-arginine
      levels remained unchanged. L-NAME administration had no effect on the neointimal
      area, nor on the luminal and total vessel area. Neointimal formation and biphasic
      vascular remodeling occur after experimental balloon dilatation of the
      nonatherosclerotic rabbit carotid artery, and can be influenced by continuous
      local perivascular delivery of L-arginine.

PMID- 10073986
TI  - A genome search identifies major quantitative trait loci on human chromosomes 3
      and 4 that influence cholesterol concentrations in small LDL particles.
AB  - Small, dense LDL particles are associated with increased risk of cardiovascular
      disease. To identify the genes that influence LDL size variation, we performed a
      genome-wide screen for cholesterol concentrations in 4 LDL size fractions.
      Samples from 470 members of randomly ascertained families were typed for 331
      microsatellite markers spaced at approximately 15 cM intervals. Plasma LDLs were
      resolved by using nondenaturing gradient gel electrophoresis into 4 fraction
      sizes (LDL-1, 26.4 to 29.0 nm; LDL-2, 25.5 to 26.4 nm; LDL-3, 24.2 to 25.5 nm;
      and LDL-4, 21.0 to 24.2 nm) and cholesterol concentrations were estimated by
      staining with Sudan Black B. Linkage analyses used variance component methods
      that exploited all of the genotypic and phenotypic information in the large
      extended pedigrees. In multipoint linkage analyses with quantitative trait loci
      for the 4 fraction sizes, only LDL-3, a fraction containing small LDL particles,
      gave peak multipoint log10 odds in favor of linkage (LOD) scores that exceeded
      3.0, a nominal criterion for evidence of significant linkage. The highest LOD
      scores for LDL-3 were found on chromosomes 3 (LOD=4.1), 4 (LOD=4.1), and 6
      (LOD=2.9). In oligogenic analyses, the 2-locus LOD score (for chromosomes 3 and
      4) increased significantly (P=0.0012) to 6.1, but including the third locus on
      chromosome 6 did not significantly improve the LOD score (P=0.064). Thus, we have
      localized 2 major quantitative trait loci that influence variation in cholesterol
      concentrations of small LDL particles. The 2 quantitative trait loci on
      chromosomes 3 and 4 are located in regions that contain the genes for apoD and
      the large subunit of the microsomal triglyceride transfer protein, respectively.

PMID- 10073987
TI  - Enzymatically modified, nonoxidized LDL induces selective adhesion and
      transmigration of monocytes and T-lymphocytes through human endothelial cell
      monolayers.
AB  - Circulating monocytes and T lymphocytes extravasate through the endothelium at
      sites of developing atheromatous lesions, where they tend to accumulate and
      mediate the progression of the disease. We have previously demonstrated the
      presence of an enzymatically degraded, nonoxidized form of LDL (E-LDL) in early
      human fatty streaks, which possesses major biological properties of an
      atherogenic lipoprotein. The effects of E-LDL on human endothelial cells have now
      been studied with respect to adhesion and transmigration of monocytes and T
      lymphocytes. E-LDL induced a rapid and dose-dependent selective adhesion of
      monocytes and T lymphocytes to endothelial cell monolayers within 30 minutes of
      incubation. Maximal increases in the number of adherent monocytes (8-fold) and of
      adherent T lymphocytes (4-fold) were observed after treatment with 50 microg/mL E
      LDL. E-LDL was more active than oxidized LDL (ox-LDL), whereas native LDL
      produced only minor adhesive effects. Both E-LDL and ox-LDL enhanced
      transmigration of monocytes and of T lymphocytes through endothelial monolayers.
      Again, E-LDL was more potent than ox-LDL, inducing transmigration to a similar
      extent as N-formyl-Met-Leu-Phe. In endothelial cells, E-LDL stimulated
      upregulation of intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial
      cells adhesion molecule-1 (PECAM-1), P-selectin, and E-selectin with distinct
      kinetics. Analyses with blocking antibodies indicated that ICAM-1 and P-selectin
      together mediated approximately 70% of cell adhesion, whereas blocking of PECAM-1
      had no effect on adhesion but reduced transmigration to less than 50% of
      controls. E-LDL also upregulated expression of ICAM-1 in human aortic smooth
      muscle cells, and this correlated with increased adhesion of T lymphocytes. E-LDL
      is thus able to promote the selective adhesion of monocytes and T lymphocytes to
      the endothelium, stimulate transmigration of these cells, and foster their
      retention in the vessel wall by increasing their adherence to smooth muscle
      cells. These findings underline the potential significance of E-LDL in the
      pathogenesis of atherosclerosis.

PMID- 10073988
TI  - Possible induction of renal dysfunction in patients with lecithin:cholesterol
      acyltransferase deficiency by oxidized phosphatidylcholine in glomeruli.
AB  - To clarify the causes of renal dysfunction in familial lecithin:cholesterol
      acyltransferase (LCAT) deficiency, kidney samples from 4 patients with LCAT
      deficiency (3 homozygotes and 1 heterozygote) were examined
      immunohistochemically. All of the patients exhibited corneal opacities, anemia,
      renal dysfunction, deficiencies in plasma high density lipoprotein and LCAT
      activity and mass, and an increase in the ratio of plasma unesterified
      cholesterol to esterified cholesterol. Renal lesions began with the deposition of
      lipidlike structures in the glomerular basement membrane, and these structures
      accumulated in the mesangium and capillary subendothelium. By electron
      microscopy, 2 types of distinctive structure were found in glomerular lesions:
      vacuole structures and cross-striated, membranelike structures. The plasma
      oxidized phosphatidylcholine (oxPC) -modified low density lipoprotein (LDL)
      levels in LCAT-deficient subjects were significantly (P<0.01) higher than those
      in controls (1.30+/-0.82 versus 0.42+/-0.32 ng/5 microg LDL, respectively), and a
      significant (P<0.01) difference was observed even after adjustment for
      confounding factors by an analysis of covariance. The patient with the highest
      plasma oxPC-modified LDL had the most membranelike structures in the glomeruli
      and showed the greatest renal deterioration from a young age. In glomerular
      lesions, although there was an abundance of apoB and apoE, oil red O-positive
      lipids, macrophages, apoA1, and malondialdehyde were scarce. OxPC was found
      extracellularly in glomerular lesions, and although its distribution differed
      from that of apolipoproteins, it was quite similar to that of phospholipids. In
      conclusion, these results indicate that oxPC in plasma and glomeruli is
      distinctive for patients with LCAT deficiency. Therefore, oxPC may be a factor in
      the deterioration of kidneys in patients with familial LCAT deficiency.

PMID- 10073989
TI  - Characterization of a new form of inherited hypercholesterolemia: familial
      recessive hypercholesterolemia.
AB  - We previously described a Sardinian family in which the probands had a severe
      form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH).
      However, low density lipoprotein (LDL) receptor activity in fibroblasts from
      these subjects and LDL binding ability were normal. The characteristics of the
      pedigree were consistent with an autosomal recessive trait. Sitosterolemia and
      pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with
      similar characteristics was identified. Probands showed severe
      hypercholesterolemia, whereas their parents and grandparents were normolipidemic.
      FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester
      storage disease were excluded by in vitro studies. We addressed the metabolic
      basis of this inherited disorder by studying the in vivo metabolism of LDL in 3
      probands from these 2 families. 125I-LDL turnover studies disclosed a marked
      reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools
      per day, respectively; P<0.001) and a significant increase in the production rate
      [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB
      in the probands compared with normolipidemic controls. We then studied the in
      vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the
      probands and compared them with those in normal controls and 1 FH homozygote. The
      probands showed a significant reduction in hepatic LDL uptake, similar to that
      observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen
      was also observed in all patients. Our findings suggest that this recessive form
      of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism.
      This appears to be caused by a selective reduction in hepatic LDL uptake. We
      propose that in this new lipid disorder, a recessive defect causes a selective
      impairment of LDL receptor function in the liver.

PMID- 10073990
TI  - Cholesteryl ester hydroperoxide lability is a key feature of the oxidative
      susceptibility of small, dense LDL.
AB  - Abundant evidence has been provided to substantiate the elevated cardiovascular
      risk associated with small, dense, low density lipoprotein (LDL) particles. The
      diminished resistance of dense LDL to oxidative stress in both normolipidemic and
      dyslipidemic subjects is established; nonetheless, the molecular basis of this
      phenomenon remains indeterminate. We have defined the primary molecular targets
      of lipid hydroperoxide formation in light, intermediate, and dense subclasses of
      LDL after copper-mediated oxidation and have compared the relative stabilities of
      the hydroperoxide derivatives of phospholipids and cholesteryl esters (CEs) as a
      function of the time course of oxidation. LDL subclasses (LDL1 through LDL5) were
      isolated from normolipidemic plasma by isopycnic density gradient
      ultracentrifugation, and their content of polyunsaturated molecular species of
      phosphatidylcholine (PC) and CE and of lipophilic antioxidants was quantified by
      reverse-phase high-performance liquid chromatography. The molar ratio of the
      particle content of polyunsaturated CE and PC species containing linoleate or
      arachidonate relative to alpha-tocopherol or beta-carotene did not differ
      significantly between LDL subspecies. Nonetheless, dense LDL contained
      significantly less polyunsaturated CE species (400 mol per particle) compared
      with LDL1 through LDL4 (range, approximately 680 to 490 mol per particle).
      Although the formation of PC-derived hydroperoxides did not vary significantly
      between LDL subspecies as a function of the time course of copper-mediated
      oxidation, the abundance of the C18:2 and C20:4 CE hydroperoxides was uniquely
      deficient in dense LDL (23 and 0.6 mol per particle, respectively, in LDL5; 47 to
      58 and 1.9 to 2.3 mol per particle, respectively, in other LDL subclasses) at
      propagation half-time. When expressed as a lability ratio (mol hydroperoxides
      formed relative to each 100 mol of substrate consumed) at half-time, the
      oxidative lability of CE hydroperoxides in dense LDL was significantly elevated
      (lability ratio <25:100) relative to that in lighter, larger LDL particle
      subclasses (lability ratio >40:100) throughout the oxidative time course. We
      conclude that the elevated lability of CE hydroperoxides in dense LDL underlies
      the diminished oxidative resistance of these particles. Moreover, this phenomenon
      appears to result not only from the significantly elevated PC to free cholesterol
      ratio (1.54:1) in dense LDL particles (1.15:1 to 1.25:1 for other LDL subclasses)
      but also from their unique structural features, including a distinct apoB100
      conformation, which may facilitate covalent bond formation between oxidized CE
      and apoB100.

PMID- 10073991
TI  - With respect to old age.

PMID- 10073992
TI  - Surgical training, supervision, and service.

PMID- 10073993
TI  - Specialist liaison nurses.

PMID- 10073994
TI  - Haemolytic uraemic syndrome and E coli O157.

PMID- 10073995
TI  - Hand washing.

PMID- 10073996
TI  - Not enough evidence to justify ovarian cancer screening.

PMID- 10073997
TI  - Parents of people with Down's syndrome report suboptimal care.

PMID- 10073998
TI  - In brief 

PMID- 10073999
TI  - UK obstetricians face redundancy 

PMID- 10074001
TI  - Philippines tackles air pollution.

PMID- 10074000
TI  - Israel restricts fertility treatment.

PMID- 10074002
TI  - Scientists discover a gene involved in diabetes and obesity 

PMID- 10074003
TI  - AMA issues guidelines on end of life care.

PMID- 10074005
TI  - Doctors may lose sole authority to prescribe 

PMID- 10074004
TI  - Audit commission recommends home nursing shake up.

PMID- 10074007
TI  - Doctors to be advised on organ removal at necropsy.

PMID- 10074008
TI  - Review calls for improved patient identification systems for blood.

PMID- 10074009
TI  - Tissue damage is commonest cause of surgical negligence suits 

PMID- 10074010
TI  - South Korea cracks down on medical corruption.

PMID- 10074011
TI  - Iron supplemented formula milk related to reduction in psychomotor decline in
      infants from inner city areas: randomised study.
AB  - OBJECTIVE: To compare the effect of unmodified cows' milk and iron supplemented
      formula milk on psychomotor development in infants from inner city areas when
      used as the main milk source. DESIGN: Double blind, randomised intervention
      trial. SETTING: Birmingham health centre. SUBJECTS: 100 infants, mean age 7.8
      months (range 5.7 to 8.6 months), whose mothers had already elected to use
      unmodified cows' milk as their infant's milk source. INTERVENTION: Changing to an
      iron supplemented formula milk from enrolment to 18 months of age, or continuing
      with unmodified cows' milk. MAIN OUTCOME MEASURES: Developmental assessments
      using Griffiths scales at enrolment and at 18 and 24 months. RESULTS: 85
      participants completed the trial. There were no significant differences in
      haemoglobin concentration between the two groups at enrolment, but by 18 months
      of age 33% of the unmodified cows' milk group, but only 2% of the iron
      supplemented group, were anaemic (P<0.001). The experimental groups had Griffiths
      general quotient scores that were not significantly different at enrolment, but
      the scores in both groups declined during the study. By 24 months the decrease in
      the mean scores in the unmodified cows' milk group was 14.7 whereas the decrease
      in the mean scores in the iron supplemented group was 9.3 (P<0.02, 95% confidence
      interval 0.4 to 10.4). Mean subquotient scores were considerably lower in the
      unmodified cows' milk group at 24 months; significantly so for personal and
      social scores (P<0.02, 1.2 to 16.8 [corrected]). CONCLUSION: Replacing unmodified
      cows' milk with an iron supplemented formula milk up to 18 months of age in
      infants from inner city areas prevents iron deficiency anaemia and reduces the
      decline in psychomotor development seen in such infants from the second half of
      the first year.

PMID- 10074012
TI  - Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic
      twin, and non-twin siblings of patients with type 1 diabetes: prospective twin
      study.
AB  - OBJECTIVE: To test the hypothesis that non-diabetic dizygotic and monozygotic
      twin siblings of patients with type 1 diabetes have a similar high prevalence of
      islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly
      environmentally determined. DESIGN: Prospective twin study. SETTING: Two
      specialist centres for diabetes in the United States. PARTICIPANTS: Non-diabetic
      monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of
      patients with type 1 diabetes; 101 controls. MAIN OUTCOME MEASURES: Analysis of
      progression to diabetes and expression of anti-islet autoantibodies. RESULTS:
      Monozygotic twin siblings had a higher risk of progression to diabetes (12/53)
      than dizygotic twin siblings (0/30; P<0.005). At the last follow up 22 (41.5%)
      monozygotic twin siblings expressed autoantibodies compared with 6 (20%)
      dizygotic twin siblings (P<0.05), 16 (10.7%) non-twin siblings (P<0.0001), and 6
      (5.9%) controls (P<0.0001). Monozygotic twin siblings expressed multiple (>/=2)
      antibodies more often than dizygotic twin siblings (10/38 v 1/23; P<0.05). By
      life table analysis the probability of developing positive autoantibodies was
      higher among the monozygotic twin siblings bearing the diabetes associated HLA
      DQ8/DQ2 genotype than in those without this genotype (64.2% (95% confidence
      interval 32.5% to 96%) v 23.5% (7% to 40%) at 10 years of discordance; P<0.05).
      CONCLUSION: Monozygotic and dizygotic twins differ in progression to diabetes and
      expression of islet cell autoantibodies. Dizygotic twin siblings are similar to
      non-twin siblings. These two observations suggest that genetic factors play an
      important part in determination of islet cell autoimmunity, thus rejecting the
      hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in
      DQ8/DQ2 monozygotic twin siblings.

PMID- 10074013
TI  - Training in large bowel cancer surgery: observations from three prospective
      regional United Kingdom audits.

PMID- 10074014
TI  - Children born after intracytoplasmic sperm injection: population control study.

PMID- 10074015
TI  - Science commentary: what is involved in intracytoplasmic sperm injection?

PMID- 10074016
TI  - Cabbage 

PMID- 10074017
TI  - Randomised controlled trial of follow up care in general practice of patients
      with myocardial infarction and angina: final results of the Southampton heart
      integrated care project (SHIP). The SHIP Collaborative Group.
AB  - OBJECTIVE: To assess the effectiveness of a programme to coordinate and support
      follow up care in general practice after a hospital diagnosis of myocardial
      infarction or angina. DESIGN: Randomised controlled trial; stratified random
      allocation of practices to intervention and control groups. SETTING: All 67
      practices in Southampton and south west Hampshire, England. SUBJECTS: 597 adult
      patients (422 with myocardial infarction and 175 with a new diagnosis of angina)
      who were recruited during hospital admission or attendance at a chest pain clinic
      between April 1995 and September 1996. INTERVENTION: Programme to coordinate
      preventive care led by specialist liaison nurses which sought to improve
      communication between hospital and general practice and to encourage general
      practice nurses to provide structured follow up. MAIN OUTCOME MEASURES: Serum
      total cholesterol concentration, blood pressure, distance walked in 6 minutes,
      confirmed smoking cessation, and body mass index measured at 1 year follow up.
      RESULTS: Of 559 surviving patients at 1 year, 502 (90%) were followed up. There
      was no significant difference between the intervention and control groups in
      smoking (cotinine validated quit rate 19% v 20%), lipid concentrations (serum
      total cholesterol 5.80 v 5.93 mmol/l), blood pressure (diastolic pressure 84 v 85
      mm Hg), or fitness (distance walked in 6 minutes 443 v 433 m). Body mass index
      was slightly lower in the intervention group (27.4 v 28.2; P=0.08). CONCLUSIONS:
      Although the programme was effective in promoting follow up in general practice,
      it did not improve health outcome. Simply coordinating and supporting existing
      NHS care is insufficient. Ischaemic heart disease is a chronic condition which
      requires the same systematic approach to secondary prevention applied in other
      chronic conditions such as diabetes mellitus.

PMID- 10074018
TI  - Development and evaluation of complex interventions in health services research:
      case study of the Southampton heart integrated care project (SHIP). The SHIP
      Collaborative Group.

PMID- 10074020
TI  - Please, please me 

PMID- 10074019
TI  - An evidence based approach to reducing antibiotic use in children with acute
      otitis media: controlled before and after study.

PMID- 10074021
TI  - Recent advances: ophthalmology.

PMID- 10074022
TI  - ABC of labour care: place of birth.

PMID- 10074023
TI  - Better benefits for health: plan to implement the central recommendation of the
      Acheson report.

PMID- 10074024
TI  - Clinical guidelines: using clinical guidelines.

PMID- 10074025
TI  - Guideline for primary care management of dementia. Such guidelines should
      consider all relevant effective treatments.

PMID- 10074026
TI  - MONICA did not deliver on task it set out to accomplish 

PMID- 10074027
TI  - Congenital abdominal wall defects in the United Kingdom. Sources had different
      reporting patterns.

PMID- 10074028
TI  - Bruising associated with paediatric fractures. Each case should be treated
      individually.

PMID- 10074029
TI  - Arterial blood gases and acid-base balance. Knowledge of bicarbonate
      concentrations is needed to assess respiratory failure.

PMID- 10074030
TI  - Professional self respect. Professional foul?

PMID- 10074031
TI  - More laboratories should test for Dientamoeba fragilis infection.

PMID- 10074032
TI  - Compensation for needlestick injury is profoundly mistaken.

PMID- 10074033
TI  - Most doctors see consent from functionalist perspective.

PMID- 10074034
TI  - Consent of relatives is neither necessary nor sufficient for treating incompetent
      adults.

PMID- 10074036
TI  - Control of multidrug resistant tuberculosis. DOTS-plus strategy will be hard to
      implement.

PMID- 10074035
TI  - Full information about trials might be given retrospectively to participants.

PMID- 10074037
TI  - National cancer centre is good idea.

PMID- 10074038
TI  - Dermatology opinions via intranet could reduce waiting times.

PMID- 10074039
TI  - Authors defend methods used in their paper.

PMID- 10074040
TI  - Severe deep white matter lesions and outcome in major depressive disorder. Might
      vasculitis be cause of these lesions in elderly depressive patients?

PMID- 10074041
TI  - Ipratropium does indeed reduce admissions to hospital with severe asthma.

PMID- 10074042
TI  - UK trial of extracorporeal membrane oxygenation gave biased estimate of efficacy.

PMID- 10074044
TI  - Debate on viagra must extend to rationing 

PMID- 10074043
TI  - Martin kwame kari kari frimpong 

PMID- 10074045
TI  - GPC regional representatives 1999-2002 

PMID- 10074047
TI  - Sports medicine: practical guidelines for general practice 

PMID- 10074046
TI  - Life without disease: the pursuit of medical utopia 

PMID- 10074048
TI  - Mount misery 

PMID- 10074049
TI  - Current medical diagnosis and treatment 1998 

PMID- 10074050
TI  - Emergency soaps 

PMID- 10074052
TI  - In memory of annie 

PMID- 10074051
TI  - Website of the week 

PMID- 10074054
TI  - Staff: the major asset of a health service 

PMID- 10074053
TI  - Church parade 

PMID- 10074055
TI  - Formula milk reduces psychomotor decline in infants from inner city areas 

PMID- 10074056
TI  - Islet cell autoimmunity is genetically determined 

PMID- 10074057
TI  - Secondary prevention of heart disease needs to be systematic 

PMID- 10074058
TI  - Intracytoplasmic sperm injection does not slow cognitive development 

PMID- 10074059
TI  - Avoiding antibiotics for acute otitis media reduces community load 

PMID- 10074060
TI  - Surface motility of serratia liquefaciens MG1.

PMID- 10074061
TI  - Aspartate kinase-independent lysine synthesis in an extremely thermophilic
      bacterium, Thermus thermophilus: lysine is synthesized via alpha-aminoadipic acid
      not via diaminopimelic acid.
AB  - An aspartate kinase-deficient mutant of Thermus thermophilus, AK001, was
      constructed. The mutant strain did not grow in a minimal medium, suggesting that
      T. thermophilus contains a single aspartate kinase. Growth of the mutant strain
      was restored by addition of both threonine and methionine, while addition of
      lysine had no detectable effect on growth. To further elucidate the lysine
      biosynthetic pathway in T. thermophilus, lysine auxotrophic mutants of T.
      thermophilus were obtained by chemical mutagenesis. For all lysine auxotrophic
      mutants, growth in a minimal medium was not restored by addition of
      diaminopimelic acid, whereas growth of two mutants was restored by addition of
      alpha-aminoadipic acid, a precursor of lysine in biosynthetic pathways of yeast
      and fungi. A BamHI fragment of 4.34 kb which complemented the lysine auxotrophy
      of a mutant was cloned. Determination of the nucleotide sequence suggested the
      presence of homoaconitate hydratase genes, termed hacA and hacB, which could
      encode large and small subunits of homoaconitate hydratase, in the cloned
      fragment. Disruption of the chromosomal copy of hacA yielded mutants showing
      lysine auxotrophy which was restored by addition of alpha-aminoadipic acid or
      alpha-ketoadipic acid. All of these results indicated that in T. thermophilus,
      lysine was not synthesized via the diaminopimelic acid pathway, believed to be
      common to all bacteria, but via a pathway using alpha-aminoadipic acid as a
      biosynthetic intermediate.

PMID- 10074062
TI  - Identification and characterization of a DeoR-specific operator sequence
      essential for induction of dra-nupC-pdp operon expression in Bacillus subtilis.
AB  - The deoR gene located just upstream the dra-nupC-pdp operon of Bacillus subtilis
      encodes the DeoR repressor protein that negatively regulates the expression of
      the operon at the level of transcription. The control region upstream of the
      operon was mapped by the use of transcriptional lacZ fusions. It was shown that
      all of the cis-acting elements, which were necessary for full DeoR regulation of
      the operon, were included in a 141-bp sequence just upstream of dra. The
      increased copy number of this control region resulted in titration of the DeoR
      molecules of the cell. By using mutagenic PCR and site-directed mutagenesis
      techniques, a palindromic sequence located from position -60 to position -43
      relative to the transcription start point was identified as a part of the
      operator site for the binding of DeoR. Furthermore, it was shown that a direct
      repeat of five nucleotides, which was identical to the 3' half of the palindrome
      and was located between the -10 and -35 regions of the dra promoter, might
      function as a half binding site involved in cooperative binding of DeoR to the
      regulatory region. Binding of DeoR protein to the operator DNA was confirmed by a
      gel electrophoresis mobility shift assay. Moreover, deoxyribose-5-phosphate was
      shown to be a likely candidate for the true inducer of the dra-nupC-pdp
      expression.

PMID- 10074063
TI  - A cold shock-induced cyanobacterial RNA helicase.
AB  - The ability to modify RNA secondary structure is crucial for numerous cellular
      processes. We have characterized two RNA helicase genes, crhB and crhC, which are
      differentially expressed in the cyanobacterium Anabaena sp. strain PCC 7120. crhC
      transcription is limited specifically to cold shock conditions while crhB is
      expressed under a variety of conditions, including enhanced expression in the
      cold. This implies that both RNA helicases are involved in the cold acclimation
      process in cyanobacteria; however, they presumably perform different roles in
      this adaptation. Although both CrhB and CrhC belong to the DEAD box subfamily of
      RNA helicases, CrhC encodes a novel RNA helicase, as the highly conserved SAT
      motif is modified to FAT. This alteration may affect CrhC function and its
      association with specific RNA targets and/or accessory proteins, interactions
      required for cold acclimation. Primer extension and analysis of the 5'
      untranslated region of crhC revealed the transcriptional start site, as well as a
      number of putative cold shock-responsive elements. The potential role(s)
      performed by RNA helicases in the acclimation of cyanobacteria to cold shock is
      discussed.

PMID- 10074064
TI  - Physiological states of individual Salmonella typhimurium cells monitored by in
      situ reverse transcription-PCR.
AB  - The possibility of using levels of specific mRNAs in individual bacteria as
      indicators of single-cell physiology was investigated. Estimates of the numbers
      of groEL and tsf mRNAs per cell in Salmonella typhimurium cells in different
      physiological states were obtained by Northern analysis. The average number of
      groEL mRNAs per cell was estimated to be 22 in fast-growing cultures and 197 in
      heat-shocked cultures. The average number of tsf mRNAs per cell was estimated to
      be 37 in fast-growing cultures, 4 in slow-growing cultures, and 0 in nongrowing
      cultures. The potential of mRNA-targeted in situ reverse transcription (RT)-PCR
      to monitor quantitatively different levels of groEL and tsf mRNA in individual
      cells and thus monitor both specific gene induction and general growth activity
      was assessed. Neither groEL nor tsf mRNA was present in stationary-phase cells,
      but it was shown that stationary-phase cells contain other RNA species at high
      levels, which may provide a possibility for monitoring directly stationary-phase
      individual cells by the use of in situ RT-PCR. The outcome of the in situ RT-PCR
      analyses indicated that a population of fast-growing cells is heterogeneous with
      respect to groEL mRNA single-cell contents, suggesting a cell-cycle-controlled
      expression of groEL in S. typhimurium, whereas a fast-growing culture is
      homogeneous with respect to tsf mRNA single-cell contents, suggesting that the
      level of tsf mRNA is relatively constant during the cell cycle.

PMID- 10074065
TI  - Tyrosine aminotransferase catalyzes the final step of methionine recycling in
      Klebsiella pneumoniae.
AB  - An aminotransferase which catalyzes the final step in methionine recycling from
      methylthioadenosine, the conversion of alpha-ketomethiobutyrate to methionine,
      has been purified from Klebsiella pneumoniae and characterized. The enzyme was
      found to be a homodimer of 45-kDa subunits, and it catalyzed methionine formation
      primarily using aromatic amino acids and glutamate as the amino donors.
      Histidine, leucine, asparagine, and arginine were also functional amino donors
      but to a lesser extent. The N-terminal amino acid sequence of the enzyme was
      determined and found to be almost identical to the N-terminal sequence of both
      the Escherichia coli and Salmonella typhimurium tyrosine aminotransferases (tyrB
      gene products). The structural gene for the tyrosine aminotransferase was cloned
      from K. pneumoniae and expressed in E. coli. The deduced amino acid sequence
      displayed 83, 80, 38, and 34% identity to the tyrosine aminotransferases from E.
      coli, S. typhimurium, Paracoccus denitrificans, and Rhizobium meliloti,
      respectively, but it showed less than 13% identity to any characterized
      eukaryotic tyrosine aminotransferase. Structural motifs around key invariant
      residues placed the K. pneumoniae enzyme within the Ia subfamily of
      aminotransferases. Kinetic analysis of the aminotransferase showed that reactions
      of an aromatic amino acid with alpha-ketomethiobutyrate and of glutamate with
      alpha-ketomethiobutyrate proceed as favorably as the well-known reactions of
      tyrosine with alpha-ketoglutarate and tyrosine with oxaloacetate normally
      associated with tyrosine aminotransferases. The aminotransferase was inhibited by
      the aminooxy compounds canaline and carboxymethoxylamine but not by substrate
      analogues, such as nitrotyrosine or nitrophenylalanine.

PMID- 10074066
TI  - Role of the alternative sigma factor sigmaS in expression of the AlkS regulator
      of the Pseudomonas oleovorans alkane degradation pathway.
AB  - The AlkS protein activates transcription from the PalkB promoter, allowing the
      expression of a number of genes required for the assimilation of alkanes in
      Pseudomonas oleovorans. We have identified the promoter from which the alkS gene
      is transcribed, PalkS, and analyzed its expression under different conditions and
      genetic backgrounds. Transcription from PalkS was very low during the exponential
      phase of growth and increased considerably when cells reached the stationary
      phase. The PalkS -10 region was similar to the consensus described for promoters
      recognized by Escherichia coli RNA polymerase bound to the alternative sigma
      factor sigmaS, which directs the expression of many stationary-phase genes.
      Reporter strains containing PalkS-lacZ transcriptional fusions showed that PalkS
      promoter is very weakly expressed in a Pseudomonas putida strain bearing an
      inactivated allele of the gene coding for sigmaS, rpoS. When PalkS was
      transferred to E. coli, transcription started at the same site and expression was
      higher in stationary phase only if sigmaS-RNA polymerase was present. The low
      levels of AlkS protein generated in the absence of sigmaS were enough to support
      a partial induction of the PalkB promoter. The -10 and -35 regions of PalkS
      promoter also show some similarity to the consensus recognized by sigmaD-RNA
      polymerase, the primary form of RNA polymerase. We propose that in exponential
      phase PalkS is probably recognized both by sigmaD-RNA polymerase (inefficiently)
      and by sigmaS-RNA polymerase (present at low levels), leading to low-level
      expression of the alkS gene. sigmaS-RNA polymerase would be responsible for the
      high level of activity of PalkS observed in stationary phase.

PMID- 10074067
TI  - Characterization of the dimerization domain in BglG, an RNA-binding
      transcriptional antiterminator from Escherichia coli.
AB  - The Escherichia coli transcriptional antiterminator protein BglG inhibits
      transcription termination of the bgl operon in response to the presence of beta
      glucosides in the growth medium. BglG is an RNA-binding protein that recognizes a
      specific sequence partially overlapping the two terminators within the bgl
      transcript. The activity of BglG is determined by its dimeric state which is
      modulated by reversible phosphorylation. Thus, only the nonphosphorylated dimer
      binds to the RNA target site and allows readthrough of transcription. Genetic
      systems which test dimerization and antitermination in vivo were used to map and
      delimit the region which mediates BglG dimerization. We show that the last 104
      residues of BglG are required for dimerization. Any attempt to shorten this
      region from the ends or to introduce internal deletions abolished the
      dimerization capacity of this region. A putative leucine zipper motif is located
      at the N terminus of this region. The role of the canonical leucines in
      dimerization was demonstrated by their substitution. Our results also suggest
      that the carboxy-terminal 70 residues, which follow the leucine zipper, contain
      another dimerization domain which does not resemble any known dimerization motif.
      Each of these two regions is necessary but not sufficient for dimerization. The
      BglG phosphorylation site, His208, resides at the junction of the two putative
      dimerization domains. Possible mechanisms by which the phosphorylation of BglG
      controls its dimerization and thus its activity are discussed.

PMID- 10074068
TI  - Sequence of Shiga toxin 2 phage 933W from Escherichia coli O157:H7: Shiga toxin
      as a phage late-gene product.
AB  - Lysogenic bacteriophages are major vehicles for the transfer of genetic
      information between bacteria, including pathogenicity and/or virulence
      determinants. In the enteric pathogen Escherichia coli O157:H7, which causes
      hemorrhagic colitis and hemolytic-uremic syndrome, Shiga toxins 1 and 2 (Stx1 and
      Stx2) are phage encoded. The sequence and analysis of the Stx2 phage 933W is
      presented here. We find evidence that the toxin genes are part of a late-phage
      transcript, suggesting that toxin production may be coupled with, if not
      dependent upon, phage release during lytic growth. Another phage gene, stk,
      encodes a product resembling eukaryotic serine/threonine protein kinases. Based
      on its position in the sequence, Stk may be produced by the prophage in the
      lysogenic state, and, like the YpkA protein of Yersinia species, it may interfere
      with the signal transduction pathway of the mammalian host. Three novel tRNA
      genes present in the phage genome may serve to increase the availability of rare
      tRNA species associated with efficient expression of pathogenicity determinants:
      both the Shiga toxin and serine/threonine kinase genes contain rare isoleucine
      and arginine codons. 933W also has homology to lom, encoding a member of a family
      of outer membrane proteins associated with virulence by conferring the ability to
      survive in macrophages, and bor, implicated in serum resistance.

PMID- 10074069
TI  - Organization of biogenesis genes for aggregative adherence fimbria II defines a
      virulence gene cluster in enteroaggregative Escherichia coli.
AB  - Several virulence-related genes have been described for prototype
      enteroaggregative Escherichia coli (EAEC) strain 042, which has been shown to
      cause diarrhea in human volunteers. Among these factors are the enterotoxins Pet
      and EAST and the fimbrial antigen aggregative adherence fimbria II (AAF/II), all
      of which are encoded on the 65-MDa virulence plasmid pAA2. Using nucleotide
      sequence analysis and insertional mutagenesis, we have found that the genes
      required for the expression of each of these factors, as well as the
      transcriptional activator of fimbrial expression AggR, map to a distinct cluster
      on the pAA2 plasmid map. The cluster is 23 kb in length and includes two regions
      required for expression of the AAF/II fimbria. These fimbrial biogenesis genes
      feature a unique organization in which the chaperone, subunit, and
      transcriptional activator lie in one cluster, whereas the second, unlinked
      cluster comprises a silent chaperone gene, usher, and invasin reminiscent of Dr
      family fimbrial clusters. This plasmid-borne virulence locus may represent an
      important set of virulence determinants in EAEC strains.

PMID- 10074070
TI  - Functional identification of the product of the Bacillus subtilis yvaL gene as a
      SecG homologue.
AB  - Protein export in Escherichia coli is mediated by translocase, a multisubunit
      membrane protein complex with SecA as the peripheral subunit and the SecY, SecE,
      and SecG proteins as the integral membrane domain. In the gram-positive bacterium
      Bacillus subtilis, SecA, SecY, and SecE have been identified through genetic
      analysis. Sequence comparison of the Bacillus chromosome identified a potential
      homologue of SecG, termed YvaL. A chromosomal disruption of the yvaL gene results
      in mild cold sensitivity and causes a beta-lactamase secretion defect. The cold
      sensitivity is exacerbated by overexpression of the secretory protein alpha
      amylase, whereas growth and beta-lactamase secretion are restored by coexpression
      of yvaL or the E. coli secG gene. These results indicate that the yvaL gene codes
      for a protein that is functionally homologous to SecG.

PMID- 10074071
TI  - Uracil-induced down-regulation of the yeast uracil permease.
AB  - In Saccharomyces cerevisiae the FUR4-encoded uracil permease catalyzes the first
      step of the pyrimidine salvage pathway. The availability of uracil has a negative
      regulatory effect upon its own transport. Uracil causes a decrease in the level
      of uracil permease, partly by decreasing the FUR4 mRNA level in a promoter
      independent fashion, probably by increasing its instability. Uracil entry also
      triggers more rapid degradation of the existing permease by promoting high
      efficiency of ubiquitination of the permease that signals its internalization. A
      direct binding of intracellular uracil to the permease is possibly involved in
      this feedback regulation, as the behavior of the permease is similar in mutant
      cells unable to convert intracellular uracil into UMP. We used cells impaired in
      the ubiquitination step to show that the addition of uracil produces rapid
      inhibition of uracil transport. This may be the first response prior to the
      removal of the permease from the plasma membrane. Similar down-regulation of
      uracil uptake, involving several processes, was observed under adverse conditions
      mainly corresponding to a decrease in the cellular content of ribosomes. These
      results suggest that uracil of exogenous or catabolic origin down-regulates the
      cognate permease to prevent buildup of excess intracellular uracil-derived
      nucleotides.

PMID- 10074072
TI  - Sequence analysis of scaffolding protein CipC and ORFXp, a new cohesin-containing
      protein in Clostridium cellulolyticum: comparison of various cohesin domains and
      subcellular localization of ORFXp.
AB  - The gene encoding the scaffolding protein of the cellulosome from Clostridium
      cellulolyticum, whose partial sequence was published earlier (S. Pages, A.
      Belaich, C. Tardif, C. Reverbel-Leroy, C. Gaudin, and J.-P. Belaich, J.
      Bacteriol. 178:2279-2286, 1996; C. Reverbel-Leroy, A. Belaich, A. Bernadac, C.
      Gaudin, J. P. Belaich, and C. Tardif, Microbiology 142:1013-1023, 1996), was
      completely sequenced. The corresponding protein, CipC, is composed of a cellulose
      binding domain at the N terminus followed by one hydrophilic domain (HD1), seven
      highly homologous cohesin domains (cohesin domains 1 to 7), a second hydrophilic
      domain, and a final cohesin domain (cohesin domain 8) which is only 57 to 60%
      identical to the seven other cohesin domains. In addition, a second gene located
      8.89 kb downstream of cipC was found to encode a three-domain protein, called
      ORFXp, which includes a cohesin domain. By using antiserum raised against the
      latter, it was observed that ORFXp is associated with the membrane of C.
      cellulolyticum and is not detected in the cellulosome fraction. Western blot and
      BIAcore experiments indicate that cohesin domains 1 and 8 from CipC recognize the
      same dockerins and have similar affinity for CelA (Ka = 4.8 x 10(9) M-1) whereas
      the cohesin from ORFXp, although it is also able to bind all cellulosome
      components containing a dockerin, has a 19-fold lower Ka for CelA (2.6 x 10(8) M
      1). Taken together, these data suggest that ORFXp may play a role in cellulosome
      assembly.

PMID- 10074073
TI  - Analysis of elements involved in pseudoknot-dependent expression and regulation
      of the repA gene of an IncL/M plasmid.
AB  - Replication of the IncL/M plasmid pMU604 is controlled by a small antisense RNA
      molecule (RNAI), which, by inhibiting the formation of an RNA pseudoknot,
      regulates translation of the replication initiator protein, RepA. Efficient
      translation of the repA mRNA was shown to require the translation and correct
      termination of the leader peptide, RepB, and the formation of the pseudoknot.
      Although the pseudoknot was essential for the expression of repA, its presence
      was shown to interfere with the translation of repB. The requirement for
      pseudoknot formation could in large part be obviated by improving the ribosome
      binding region of repA, either by replacing the GUG start codon by AUG or by
      increasing the spacing between the start codon and the Shine-Dalgarno sequence
      (SD). The spacing between the distal pseudoknot sequence and the repA SD was
      shown to be suboptimal for maximal expression of repA.

PMID- 10074075
TI  - CspA, CspB, and CspG, major cold shock proteins of Escherichia coli, are induced
      at low temperature under conditions that completely block protein synthesis.
AB  - CspA, CspB, and CspG, the major cold shock proteins of Escherichia coli, are
      dramatically induced upon temperature downshift. In this report, we examined the
      effects of kanamycin and chloramphenicol, inhibitors of protein synthesis, on
      cold shock inducibility of these proteins. Cell growth was completely blocked at
      37 degrees C in the presence of kanamycin (100 microgram/ml) or chloramphenicol
      (200 microgram/ml). After 10 min of incubation with the antibiotics at 37 degrees
      C, cells were cold shocked at 15 degrees C and labeled with [35S]methionine at 30
      min after the cold shock. Surprisingly, the synthesis of all these cold shock
      proteins was induced at a significantly high level virtually in the absence of
      synthesis of any other protein, indicating that the cold shock proteins are able
      to bypass the inhibitory effect of the antibiotics. Possible bypass mechanisms
      are discussed. The levels of cspA and cspB mRNAs for the first hour at 15 degrees
      C were hardly affected in the absence of new protein synthesis caused either by
      antibiotics or by amino acid starvation.

PMID- 10074074
TI  - Differential dependence of levansucrase and alpha-amylase secretion on SecA (Div)
      during the exponential phase of growth of Bacillus subtilis.
AB  - SecA, the translocation ATPase of the preprotein translocase, accounts for 0.25%
      of the total protein in a degU32(Hy) Bacillus subtilis strain in logarithmic
      phase. The SecA level remained constant irrespective of the demand for exoprotein
      production but dropped about 12-fold during the late stationary phase. Modulation
      of the level of functional SecA during the exponential phase of growth affected
      differently the secretion of levansucrase and alpha-amylase overexpressed under
      the control of the sacB leader region. The level of SecA was reduced in the
      presence of sodium azide and in the div341 thermosensitive mutant at
      nonpermissive temperatures. Overproduction of SecA was obtained with a multicopy
      plasmid bearing secA. The gradual decrease of the SecA level reduced the yield of
      secreted levansucrase with a concomitant accumulation of unprocessed precursor in
      the cells, while an increase in the SecA level resulted in an elevation of the
      production of exocellular levansucrase. In contrast, alpha-amylase secretion was
      almost unaffected by high concentrations of sodium azide or by very low levels of
      SecA. Secretion defects were apparent only under conditions of strong SecA
      deprivation of the cell. These data demonstrate that the alpha-amylase and
      levansucrase precursors markedly differ in their dependency on SecA for
      secretion. It is suggested that these precursors differ in their binding
      affinities for SecA.

PMID- 10074076
TI  - Aspartate 205 in the catalytic domain of naphthalene dioxygenase is essential for
      activity.
AB  - The naphthalene dioxygenase enzyme system carries out the first step in the
      aerobic degradation of naphthalene by Pseudomonas sp. strain NCIB 9816-4. The
      crystal structure of naphthalene dioxygenase (B. Kauppi, K. Lee, E. Carredano, R.
      E. Parales, D. T. Gibson, H. Eklund, and S. Ramaswamy, Structure 6:571-586, 1998)
      indicates that aspartate 205 may provide the most direct route of electron
      transfer between the Rieske [2Fe-2S] center of one alpha subunit and mononuclear
      iron in the adjacent alpha subunit. In this study, we constructed four site
      directed mutations that changed aspartate 205 to alanine, glutamate, asparagine,
      or glutamine to test whether this residue is essential for naphthalene
      dioxygenase activity. The mutant proteins were very inefficient in oxidizing
      naphthalene to cis-naphthalene dihydrodiol, and oxygen uptake in the presence of
      naphthalene was below detectable levels. The purified mutant protein with
      glutamine in place of aspartate 205 had identical spectral properties to wild
      type naphthalene dioxygenase and was reduced by NADH in the presence of catalytic
      amounts of ferredoxinNAP and reductaseNAP. Benzene, an effective uncoupler of
      oxygen consumption in purified naphthalene dioxygenase, did not elicit oxygen
      uptake by the mutant protein. These results indicate that electron transfer from
      NADH to the Rieske center in the mutant oxygenase is intact, a finding consistent
      with the proposal that aspartate 205 is a necessary residue in the major pathway
      of electron transfer to mononuclear iron at the active site.

PMID- 10074077
TI  - Characterization of the ssnA gene, which is involved in the decline of cell
      viability at the beginning of stationary phase in Escherichia coli.
AB  - When grown in rich medium, Escherichia coli exhibits a drastic reduction of the
      number of viable cells at the beginning of stationary phase. The decline of cell
      viability was retarded by disruption of the ssnA gene, which was identified as a
      gene subject to RpoS-dependent negative regulation. Moreover, ssnA expression was
      induced at the time of decline of cell viability at early stationary phase. The
      viability decline was augmented in the rpoS background, and this augmentation was
      suppressed by ssnA mutation. Cloning of the ssnA gene in a multicopy plasmid,
      pBR322, caused small colony formation and slow growth in liquid medium. Cells
      harboring the ssnA clone showed aberrant morphology that included enlarged and
      filamentous shapes. The gene product was identified as a 44-kDa soluble protein,
      but its function could not be deduced by homology searching. From these results,
      we conclude that ssnA is expressed in response to a phase-specific signal(s) and
      that its expression level is controlled by RpoS, by a mechanism which may
      contribute to determination of cell number in the stationary phase.

PMID- 10074078
TI  - Identification of the tliDEF ABC transporter specific for lipase in Pseudomonas
      fluorescens SIK W1.
AB  - Pseudomonas fluorescens, a gram-negative psychrotrophic bacterium, secretes a
      thermostable lipase into the extracellular medium. In our previous study, the
      lipase of P. fluorescens SIK W1 was cloned and expressed in Escherichia coli, but
      it accumulated as inactive inclusion bodies. Amino acid sequence analysis of the
      lipase revealed a potential C-terminal targeting sequence recognized by the ATP
      binding cassette (ABC) transporter. The genetic loci around the lipase gene were
      searched, and a secretory gene was identified. Nucleotide sequencing of an 8.5-kb
      DNA fragment revealed three components of the ABC transporter, tliD, tliE, and
      tliF, upstream of the lipase gene, tliA. In addition, genes encoding a protease
      and a protease inhibitor were located upstream of tliDEF. tliDEF showed high
      similarity to ABC transporters of Pseudomonas aeruginosa alkaline protease,
      Erwinia chrysanthemi protease, Serratia marcescens lipase, and Pseudomonas
      fluorescens CY091 protease. tliDEF and the lipase structural gene in a single
      operon were sufficient for E. coli cells to secrete the lipase. In addition, E.
      coli harboring the lipase gene secreted the lipase by complementation of tliDEF
      in a different plasmid. The ABC transporter of P. fluorescens was optimally
      functional at 20 and 25 degrees C, while the ABC transporter, aprD, aprE, and
      aprF, of P. aeruginosa secreted the lipase irrespective of temperature between 20
      and 37 degrees C. These results demonstrated that the lipase is secreted by the
      P. fluorescens SIK W1 ABC transporter, which is organized as an operon with tliA,
      and that its secretory function is temperature dependent.

PMID- 10074079
TI  - Cloning of mnuA, a membrane nuclease gene of Mycoplasma pulmonis, and analysis of
      its expression in Escherichia coli.
AB  - Membrane nucleases of mycoplasmas are believed to play important roles in growth
      and pathogenesis, although no clear evidence for their importance has yet been
      obtained. As a first step in defining the function of this unusual membrane
      activity, studies were undertaken to clone and analyze one of the membrane
      nuclease genes from Mycoplasma pulmonis. A novel screening strategy was used to
      identify a recombinant lambda phage expressing nuclease activity, and its cloned
      fragment was analyzed. Transposon mutagenesis was used to identify an open
      reading frame of 1,410 bp, which coded for nuclease activity in Escherichia coli.
      This gene coded for a 470-amino-acid polypeptide of 53,739 Da and was designated
      mnuA (for "membrane nuclease"). The MnuA protein contained a prolipoprotein
      signal peptidase II recognition sequence along with an extensive hydrophobic
      region near the amino terminus, suggesting that the protein may be lipid modified
      or that it is anchored in the membrane by this membrane-spanning region. Antisera
      raised against two MnuA peptide sequences identified an M. pulmonis membrane
      protein of approximately 42 kDa by immunoblotting, which corresponded to a
      trypsin-sensitive nucleolytic band of the same size. Maxicell experiments with E.
      coli confirmed that mnuA coded for a nuclease of unknown specificity.
      Hybridization studies showed that mnuA sequences are found in few Mycoplasma
      species, suggesting that mycoplasma membrane nucleases display significant
      sequence variation within the genus Mycoplasma.

PMID- 10074080
TI  - Purification and characterization of two extremely thermostable enzymes,
      phosphate acetyltransferase and acetate kinase, from the hyperthermophilic
      eubacterium Thermotoga maritima.
AB  - Phosphate acetyltransferase (PTA) and acetate kinase (AK) of the
      hyperthermophilic eubacterium Thermotoga maritima have been purified 1,500- and
      250-fold, respectively, to apparent homogeneity. PTA had an apparent molecular
      mass of 170 kDa and was composed of one subunit with a molecular mass of 34 kDa,
      suggesting a homotetramer (alpha4) structure. The N-terminal amino acid sequence
      showed significant identity to that of phosphate butyryltransferases from
      Clostridium acetobutylicum rather than to those of known phosphate
      acetyltransferases. The kinetic constants of the reversible enzyme reaction
      (acetyl-CoA + Pi -->/<-- acetyl phosphate + CoA) were determined at the pH
      optimum of pH 6.5. The apparent Km values for acetyl-CoA, Pi, acetyl phosphate,
      and coenzyme A (CoA) were 23, 110, 24, and 30 microM, respectively; the apparent
      Vmax values (at 55 degrees C) were 260 U/mg (acetyl phosphate formation) and 570
      U/mg (acetyl-CoA formation). In addition to acetyl-CoA (100%), the enzyme
      accepted propionyl-CoA (60%) and butyryl-CoA (30%). The enzyme had a temperature
      optimum at 90 degrees C and was not inactivated by heat upon incubation at 80
      degrees C for more than 2 h. AK had an apparent molecular mass of 90 kDa and
      consisted of one 44-kDa subunit, indicating a homodimer (alpha2) structure. The N
      terminal amino acid sequence showed significant similarity to those of all known
      acetate kinases from eubacteria as well that of the archaeon Methanosarcina
      thermophila. The kinetic constants of the reversible enzyme reaction (acetyl
      phosphate + ADP -->/<-- acetate + ATP) were determined at the pH optimum of pH
      7.0. The apparent Km values for acetyl phosphate, ADP, acetate, and ATP were
      0.44, 3, 40, and 0.7 mM, respectively; the apparent Vmax values (at 50 degrees C)
      were 2,600 U/mg (acetate formation) and 1,800 U/mg (acetyl phosphate formation).
      AK phosphorylated propionate (54%) in addition to acetate (100%) and used GTP
      (100%), ITP (163%), UTP (56%), and CTP (21%) as phosphoryl donors in addition to
      ATP (100%). Divalent cations were required for activity, with Mn2+ and Mg2+ being
      most effective. The enzyme had a temperature optimum at 90 degrees C and was
      stabilized against heat inactivation by salts. In the presence of (NH4)2SO4 (1
      M), which was most effective, the enzyme did not lose activity upon incubation at
      100 degrees C for 3 h. The temperature optimum at 90 degrees C and the high
      thermostability of both PTA and AK are in accordance with their physiological
      function under hyperthermophilic conditions.

PMID- 10074081
TI  - Rapid hypothesis testing with Candida albicans through gene disruption with short
      homology regions.
AB  - Disruption of newly identified genes in the pathogen Candida albicans is a vital
      step in determination of gene function. Several gene disruption methods described
      previously employ long regions of homology flanking a selectable marker. Here, we
      describe disruption of C. albicans genes with PCR products that have 50 to 60 bp
      of homology to a genomic sequence on each end of a selectable marker. We used the
      method to disrupt two known genes, ARG5 and ADE2, and two sequences newly
      identified through the Candida genome project, HRM101 and ENX3. HRM101 and ENX3
      are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC
      pathways of Saccharomyces cerevisiae and Aspergillus nidulans. We show that three
      independent hrm101/hrm101 mutants and two independent enx3/enx3 mutants are
      defective in filamentation on Spider medium. These observations argue that HRM101
      and ENX3 sequences are indeed portions of genes and that the respective gene
      products have related functions.

PMID- 10074082
TI  - In vivo role of catalase-peroxidase in synechocystis sp. strain PCC 6803.
AB  - The katG gene coding for the only catalase-peroxidase in the cyanobacterium
      Synechocystis sp. strain PCC 6803 was deleted in this organism. Although the rate
      of H2O2 decomposition was about 30 times lower in the DeltakatG mutant than in
      the wild type, the strain had a normal phenotype and its doubling time as well as
      its resistance to H2O2 and methyl viologen were indistinguishable from those of
      the wild type. The residual H2O2-scavenging capacity was more than sufficient to
      deal with the rate of H2O2 production by the cell, estimated to be less than 1%
      of the maximum rate of photosynthetic electron transport in vivo. We propose that
      catalase-peroxidase has a protective role against environmental H2O2 generated by
      algae or bacteria in the ecosystem (for example, in mats). This protective role
      is most apparent at a high cell density of the cyanobacterium. The residual H2O2
      scavenging activity in the DeltakatG mutant was a light-dependent peroxidase
      activity. However, neither glutathione peroxidase nor ascorbate peroxidase
      accounted for a significant part of this H2O2-scavenging activity. When a small
      thiol such as dithiothreitol was added to the medium, the rate of H2O2
      decomposition in the DeltakatG mutant increased more than 10-fold, indicating
      that a thiol-specific peroxidase, for which thioredoxin may be the physiological
      electron donor, is present. Oxidized thioredoxin is likely to be reduced again by
      photosynthetic electron transport. Therefore, under laboratory conditions, there
      are only two enzymatic mechanisms for H2O2 decomposition present in Synechocystis
      sp. strain PCC 6803. One is catalyzed by a catalase-peroxidase, and the other is
      catalyzed by thiol-specific peroxidase.

PMID- 10074083
TI  - Genetic analysis of the Serratia marcescens N28b O4 antigen gene cluster.
AB  - The Serratia marcescens N28b wbbL gene has been shown to complement the rfb-50
      mutation of Escherichia coli K-12 derivatives, and a wbbL mutant has been shown
      to be impaired in O4-antigen biosynthesis (X. Rubires, F. Saigi, N. Pique, N.
      Climent, S. Merino, S. Alberti, J. M. Tomas, and M. Regue, J. Bacteriol. 179:7581
      7586, 1997). We analyzed a recombinant cosmid containing the wbbL gene by
      subcloning and determination of O-antigen production phenotype in E. coli
      DH5alpha by sodium dodecyl sulfate-polyacrylamide electrophoresis and Western
      blot experiments with S. marcescens O4 antiserum. The results obtained showed
      that a recombinant plasmid (pSUB6) containing about 10 kb of DNA insert was
      enough to induce O4-antigen biosynthesis. The same results were obtained when an
      E. coli K-12 strain with a deletion of the wb cluster was used, suggesting that
      the O4 wb cluster is located in pSUB6. No O4 antigen was produced when plasmid
      pSUB6 was introduced in a wecA mutant E. coli strain, suggesting that O4-antigen
      production is wecA dependent. Nucleotide sequence determination of the whole
      insert in plasmid pSUB6 showed seven open reading frames (ORFs). On the basis of
      protein similarity analysis of the ORF-encoded proteins and analysis of the S.
      marcescens N28b wbbA insertion mutant and wzm-wzt deletion mutant, we suggest
      that the O4 wb cluster codes for two dTDP-rhamnose biosynthetic enzymes (RmlDC),
      a rhamnosyltransferase (WbbL), a two-component ATP-binding-cassette-type export
      system (Wzm Wzt), and a putative glycosyltransferase (WbbA). A sequence showing
      DNA homology to insertion element IS4 was found downstream from the last gene in
      the cluster (wbbA), suggesting that an IS4-like element could have been involved
      in the acquisition of the O4 wb cluster.

PMID- 10074084
TI  - Catabolic repression of secB expression is positively controlled by cyclic AMP
      (cAMP) receptor protein-cAMP complexes at the transcriptional level.
AB  - SecB, a protein export-specific chaperone, enhances the export of a subset of
      proteins across cytoplasmic membranes of Escherichia coli. Previous studies
      showed that the synthesis of SecB is repressed by the presence of glucose in the
      medium. The derepression of SecB requires the products of both the cya and crp
      genes, indicating that secB expression is under the control of catabolic
      repression. In this study, two secB-specific promoters were identified. In
      addition, 5' transcription initiation sites from these two promoters were
      determined by means of secB-lacZ fusions and primer extension. The distal P1
      promoter appeared to be independent of carbon sources, whereas the proximal P2
      promoter was shown to be subject to control by the cyclic AMP (cAMP) receptor
      protein (CRP)-cAMP complexes. Gel-mobility shift studies showed that this
      regulation results from direct interaction between the secB P2 promoter region
      and the CRP-cAMP complex. Moreover, the CRP binding site on the secB gene was
      determined by DNase I footprinting and further substantiated by mutational
      analysis. The identified secB CRP binding region is centered at the -61.5 region
      of the secB gene and differed from the putative binding sites predicted by
      computer analysis.

PMID- 10074085
TI  - Nucleoid-independent identification of cell division sites in Escherichia coli.
AB  - The mechanism used by Escherichia coli to determine the correct site for cell
      division is unknown. In this report, we have attempted to distinguish between a
      model in which septal position is determined by the position of the nucleoids and
      a model in which septal position is predetermined by a mechanism that does not
      involve nucleoid position. To do this, filaments with extended nucleoid-free
      regions adjacent to the cell poles were produced by simultaneous inactivation of
      cell division and DNA replication. The positions of septa that formed within the
      nucleoid-free zones after division was allowed to resume were then analyzed. The
      results showed that septa were formed at a uniform distance from cell poles when
      division was restored, with no relation to the distance from the nearest
      nucleoid. In some cells, septa were formed directly over nucleoids. These results
      are inconsistent with models that invoke nucleoid positioning as the mechanism
      for determining the site of division site formation.

PMID- 10074086
TI  - Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by
      the PII signal transduction protein.
AB  - The nitrogen regulator II (NRII or NtrB)-NRI (NtrC) two-component signal
      transduction system regulates the transcription of nitrogen-regulated genes in
      Escherichia coli. The NRII protein has both kinase and phosphatase activities and
      catalyzes the phosphorylation and dephosphorylation of NRI, which activates
      transcription when phosphorylated. The phosphatase activity of NRII is activated
      by the PII signal transduction protein. We showed that PII was also an inhibitor
      of the kinase activity of NRII. The data were consistent with the hypothesis that
      the kinase and phosphatase activities of two-component system kinase/phosphatase
      proteins are coordinately and reciprocally regulated. The ability of PII to
      regulate NRII is allosterically controlled by the small-molecule effector 2
      ketoglutarate, which binds to PII. We studied the effect of 2-ketoglutarate on
      the regulation of the kinase and phosphatase activities of NRII by PII, using a
      coupled enzyme system to measure the rate of cleavage of ATP by NRII. The data
      were consistent with the following hypothesis: when not complexed with 2
      ketoglutarate, PII cannot bind to NRII and has no effect on its competing NRI
      kinase and phosphatase activities. Under these conditions, the kinase activity of
      NRII is dominant. At low 2-ketoglutarate concentrations, PII trimers complexed
      with a single molecule of 2-ketoglutarate interact with NRII to inhibit its
      kinase activity and activate its phosphatase activity. However, at high 2
      ketoglutarate concentrations, PII binds additional ligand molecules and is
      rendered incapable of binding to NRII, thereby releasing inhibition of NRII's
      kinase activity and effectively inhibiting its phosphatase activity (by failing
      to stimulate it).

PMID- 10074087
TI  - The cyclic AMP receptor protein is dependent on GcvA for regulation of the gcv
      operon.
AB  - The Escherichia coli gcv operon is transcriptionally regulated by the GcvA, GcvR,
      Lrp, and PurR proteins. In this study, the cyclic AMP (cAMP) receptor protein
      (CRP) is shown to be involved in positive regulation of the gcv operon. A crp
      deletion reduced expression of a gcvT-lacZ fusion almost fourfold in glucose
      minimal (GM) medium. The phenotype was complemented by both the wild-type crp
      gene and four crp alleles that encode proteins with amino acid substitutions in
      known activating regions of CRP. A cyaA deletion also resulted in a fourfold
      decrease in gcvT-lacZ expression, and wild-type expression was restored by the
      addition of cAMP to the growth medium. A cyaA crp double deletion resulted in
      levels of gcvT-lacZ expression identical to those observed with either single
      mutation, showing that CRP and cAMP regulate through the same mechanism. Growth
      in GM medium plus cAMP or glycerol minimal medium did not result in a significant
      increase in gcvT-lacZ expression. Thus, the level of cAMP present in GM medium
      appears to be sufficient for regulation by CRP. DNase I footprint analysis showed
      that CRP binds and protects two sites centered at bp -313 (site 1) and bp -140
      (site 2) relative to the transcription initiation site, but a mutational analysis
      demonstrated that only site 1 is required for CRP-mediated regulation of gcvT
      lacZ expression. Expression of the gcvT-lacZ fusion in a crp gcvA double mutant
      suggested that CRP's role is dependent on the GcvA protein.

PMID- 10074088
TI  - Site-directed mutagenesis of loop L3 of sucrose porin ScrY leads to changes in
      substrate selectivity.
AB  - The difference in substrate selectivity of the maltodextrin (LamB) and sucrose
      (ScrY) porins is attributed mainly to differences in loop L3, which is supposed
      to constrict the lumen of the pores. We show that even a single mutation (D201Y)
      in loop L3 leads to a narrowing of the substrate range of ScrY to that resembling
      LamB. In addition, we removed the putative N-terminal coiled-coil structure of
      ScrY and studied the effect of this deletion on sucrose transport.

PMID- 10074089
TI  - Characterization of the divergent sacBK and sacAR operons, involved in sucrose
      utilization by Lactococcus lactis.
AB  - The divergently transcribed sacBK and sacAR operons, which are involved in the
      utilization of sucrose by Lactococcus lactis NZ9800, were examined by
      transcriptional and gene inactivation studies. Northern analyses of RNA isolated
      from cells grown at the expense of different carbon sources revealed three
      sucrose-inducible transcripts: one of 3.2 kb containing sacB and sacK, a second
      of 3.4 kb containing sacA and sacR, and a third of 1.8 kb containing only sacR.
      The inactivation of the sacR gene by replacement recombination resulted in the
      constitutive transcription of the sacBK and sacAR operons in the presence of
      different carbon sources, indicating that SacR acts as a repressor of
      transcription.

PMID- 10074090
TI  - The polar flagellar motor of Vibrio cholerae is driven by an Na+ motive force.
AB  - Vibrio cholerae is a highly motile bacterium which possesses a single polar
      flagellum as a locomotion organelle. Motility is thought to be an important
      factor for the virulence of V. cholerae. The genome sequencing project of this
      organism is in progress, and the genes that are highly homologous to the
      essential genes of the Na+-driven polar flagellar motor of Vibrio alginolyticus
      were found in the genome database of V. cholerae. The energy source of its
      flagellar motor was investigated. We examined the Na+ dependence and the
      sensitivity to the Na+ motor-specific inhibitor of the motility of the V.
      cholerae strains and present the evidence that the polar flagellar motor of V.
      cholerae is driven by an Na+ motive force.

PMID- 10074091
TI  - Sugar- and nitrogen-dependent regulation of an Amanita muscaria phenylalanine
      ammonium lyase gene.
AB  - The cDNA of a key enzyme of secondary metabolism, phenylalanine ammonium lyase,
      was identified for an ectomycorrhizal fungus by differential screening of a
      mycorrhizal library. The gene was highly expressed in hyphae grown at low
      external monosaccharide concentrations, but its expression was 30-fold reduced at
      elevated concentrations. Gene repression was regulated by hexokinase.

PMID- 10074092
TI  - Role of ArgR in activation of the ast operon, encoding enzymes of the arginine
      succinyltransferase pathway in Salmonella typhimurium.
AB  - The ast operon, encoding enzymes of the arginine succinyltransferase (AST)
      pathway, was cloned from Salmonella typhimurium, and the nucleotide sequence for
      the upstream flanking region was determined. The control region contains several
      regulatory consensus sequences, including binding sites for NtrC, cyclic AMP
      receptor protein (CRP), and ArgR. The results of DNase I footprintings and gel
      retardation experiments confirm binding of these regulatory proteins to the
      identified sites. Exogenous arginine induced AST under nitrogen-limiting
      conditions, and this induction was abolished in an argR derivative. AST was also
      induced under carbon starvation conditions; this induction required functional
      CRP as well as functional ArgR. The combined data are consistent with the
      hypothesis that binding of one or more ArgR molecules to a region between the
      upstream binding sites for NtrC and CRP and two putative promoters plays a
      pivotal role in modulating expression of the ast operon in response to nitrogen
      or carbon limitation.

PMID- 10074093
TI  - SodA and manganese are essential for resistance to oxidative stress in growing
      and sporulating cells of Bacillus subtilis.
AB  - We constructed a sodA-disrupted mutant of Bacillus subtilis 168, BK1, by
      homologous recombination. The mutant was not able to grow in minimal medium
      without Mn(II). The spore-forming ability of strain BK1 was significantly lower
      in Mn(II)-depleted medium than that of the wild-type strain. These deleterious
      effects caused by the sodA mutation were reversed when an excess of Mn(II) was
      used to supplement the medium. Moreover, the growth inhibition by superoxide
      generators in strain BK1 and its parent strain was also reversed by the
      supplementation with excess Mn(II). We therefore estimated the Mn-dependent
      superoxide-scavenging activity in BK1 cells. Whereas BK1 cells have no detectable
      superoxide dismutase (Sod) on native gel, the superoxide-scavenging activity in
      crude extracts of BK1 cells grown in Mn(II)-supplemented LB medium (10 g of
      tryptone, 5 g of yeast extract, and 5 g of NaCl per liter) was significantly
      detected by the modified Sod assay method without using EDTA. The results
      obtained suggest that Mn, as a free ion or a complex with some cellular
      component, can catalyze the elimination of superoxide and that both SodA and
      Mn(II) are involved not only in the superoxide resistance of vegetative cells but
      also in sporulation.

PMID- 10074094
TI  - A missense mutation accounts for the defect in the glycerol-3-phosphate
      acyltransferase expressed in the plsB26 mutant.
AB  - The sn-glycerol-3-phosphate acyltransferase (plsB) catalyzes the first step in
      membrane phospholipid formation. A conditional Escherichia coli mutant (plsB26)
      has a single missense mutation (G1045A) predicting the expression of an
      acyltransferase with an Ala349Thr substitution. The PlsB26 protein had a
      significantly reduced glycerol-3-phosphate acyltransferase specific activity
      coupled with an elevated Km for glycerol-3-phosphate.

PMID- 10074095
TI  - Functional analysis of the active partition region of the Coxiella burnetii
      plasmid QpH1.
AB  - The partition region qsopAB of the Coxiella burnetii plasmid QpH1 was analyzed.
      Locus qsopA alone appears to fulfill the partitioning function; QsopA represses
      its own promoter 17-fold. Two partition-associated incompatibility sites were
      identified: incA in a 200-bp region covering the qsopA promoter and incB in the
      qsopB locus.

PMID- 10074096
TI  - Identification and cloning of an Erwinia carotovora subsp. carotovora bacteriocin
      regulator gene by insertional mutagenesis.
AB  - Avirulent Erwinia carotovora subsp. carotovora CGE234-M403 produces two types of
      bacteriocin. For the purpose of cloning the bacteriocin genes of strain
      CGE234M403, a spontaneous rifampin-resistant mutant of this strain, M-rif-11-2,
      was isolated. By Tn5 insertional mutagenesis using M-rif-11-2, a mutant, TM01A01,
      which produces the high-molecular-weight bacteriocin but not the low-molecular
      weight bacteriocin was obtained. By thermal asymmetric interlaced PCR, the DNA
      sequence from the Tn5 insertion site and the DNA sequence of a contiguous 1,280
      bp region were determined. One complete open reading frame (ORF), designated
      ORF2, was identified within the sequenced fragment. The 3' end of another ORF,
      ORF1, was located upstream of ORF2. A noncoding region and a putative promoter
      were located between ORF1 and ORF2. Downstream from ORF2, the 5' end of another
      ORF (ORF3) was found. Deduction from the nucleotide sequence indicated that ORF2
      encodes a protein of 99 amino acids, which showed high homology with Yersinia
      enterocolitica Yrp, a regulator of enterotoxin (Y-ST) production; Escherichia
      coli host factor 1, required for Qbeta-replicase; and Azorhizobium caulinodans
      NrfA, required for the expression of nifA. ORF2 was designated brg, bacteriocin
      regulator gene. A fragment containing ORF2 and its promoter was amplified and
      cloned into pBR322 and pHSG415r, and the recombinant plasmids, pBYL1 and pHYL1,
      were transferred into E. coli DH5. Plasmid pBYL1 was reisolated and transferred
      into the insertion mutant TM01A01. Transformants carrying the plasmid, which was
      reisolated and designated pBYL1, re-produced the low-molecular-weight
      bacteriocin.

PMID- 10074097
TI  - Expression of the Methanobacterium thermoautotrophicum hpt gene, encoding
      hypoxanthine (Guanine) phosphoribosyltransferase, in Escherichia coli.
AB  - The hpt gene from the archaeon Methanobacterium thermoautotrophicum, encoding
      hypoxanthine (guanine) phosphoribosyltransferase, was cloned by functional
      complementation into Escherichia coli. The hpt-encoded amino acid sequence is
      most similar to adenine phosphoribosyltransferases, but the encoded enzyme has
      activity only with hypoxanthine and guanine. The synthesis of the recombinant
      enzyme is apparently limited by the presence of the rare arginine codons AGA and
      AGG and the rare isoleucine AUA codon on the hpt gene. The recombinant enzyme was
      purified to apparent homogeneity.

PMID- 10074098
TI  - LB-AUT7, a novel symbiosis-regulated gene from an ectomycorrhizal fungus,
      Laccaria bicolor, is functionally related to vesicular transport and
      autophagocytosis.
AB  - We have identified LB-AUT7, a gene differentially expressed 6 h after
      ectomycorrhizal interaction between Laccaria bicolor and Pinus resinosa. LB-Aut7p
      can functionally complement its Saccharomyces cerevisiae homolog, which is
      involved in the attachment of autophagosomes to microtubules. Our findings
      suggest the induction of an autophagocytosis-like vesicular transport process
      during ectomycorrhizal interaction.

PMID- 10074099
TI  - Escherichia coli outer membrane protein TolC is involved in production of the
      peptide antibiotic microcin J25.
AB  - A Tn5 insertion in tolC eliminated microcin J25 production. The mutation had
      little effect on the expression of the microcin structural gene and presumably
      acted by blocking microcin secretion. The tolC mutants carrying multiple copies
      of the microcin genes were less immune to the microcin. TolC is thus likely a
      component of a microcin export complex containing the McjD immunity protein, an
      ABC exporter.

PMID- 10074100
TI  - Construction and analysis of hybrid Escherichia coli-Bacillus subtilis dnaK
      genes.
AB  - The highly conserved DnaK chaperones consist of an N-terminal ATPase domain, a
      central substrate-binding domain, and a C-terminal domain whose function is not
      known. Since Bacillus subtilis dnaK was not able to complement an Escherichia
      coli dnaK null mutant, we performed domain element swap experiments to identify
      the regions responsible for this finding. It turned out that the B. subtilis DnaK
      protein needed approximately normal amounts of the cochaperone DnaJ to be
      functional in E. coli. The ATPase domain and the substrate-binding domain form a
      species-specific functional unit, while the C-terminal domains, although less
      conserved, are exchangeable. Deletion of the C-terminal domain in E. coli DnaK
      affected neither complementation of growth at high temperatures nor propagation
      of phage lambda but abolished degradation of sigma32.

PMID- 10074101
TI  - Residues critical for duck hepatitis B virus neutralization are involved in host
      cell interaction.
AB  - To date, no detailed analysis of the neutralization properties of duck hepatitis
      B virus (DHBV) has been reported, and it is not clear whether any of the known
      neutralization epitopes correspond to the viral receptor binding site or to
      sequences involved in the cell entry pathway. We demonstrate here that antibodies
      directed against two overlapping peptides (amino acids 83 to 97 and 93 to 107),
      covering the sequences of most DHBV pre-S neutralizing epitopes, both inhibit
      virus binding to primary duck hepatocytes and neutralize virus infectivity. An
      extensive mutagenesis of the motif 88WTP90, which is the shortest sequence of the
      epitope recognized by the virus-neutralizing monoclonal antibody (MAb) 900 was
      performed in order to define the amino acids involved in these interactions.
      Single point mutations within this epitope affected neither virus replication nor
      infectivity but abolished virus neutralization by MAb 900 completely.
      Interestingly, mutants with two and three consecutive residue replacements (SIP
      and SIH) within this epitope retained replication competence but were no longer
      infectious. The loss of infectivity of SIH and SIP mutant particles was
      associated with significantly reduced binding to primary duck hepatocytes and
      could be rescued by trans complementation with wild-type pre-S protein. Taken
      together, these results indicate that each amino acid of the DHBV pre-S sequence
      88WTP90 is critical for recognition by the neutralizing MAb 900 and that
      replacement of the first two or all three residues strongly reduces virus
      interaction with hepatocytes and abrogates infectivity. These data imply that the
      motif 88WTP90 contains key residues which are critical for interaction with both
      the neutralizing MAb and the host cell.

PMID- 10074102
TI  - Effect of mutations in the second extracellular loop of CXCR4 on its utilization
      by human and feline immunodeficiency viruses.
AB  - CCR5 and CXCR4 are the principal CD4-associated coreceptors used by human
      immunodeficiency virus type 1 (HIV-1). CXCR4 is also a receptor for the feline
      immunodeficiency virus (FIV). The rat CXCR4 cannot mediate infection by HIV-1NDK
      or by FIVPET (both cell line-adapted strains) because of sequence differences
      with human CXCR4 in the second extracellular loop (ECL2). Here we made similar
      observations for HIV-189.6 (a strain also using CCR5) and for a primary HIV-1
      isolate. It showed the role of ECL2 in the coreceptor activity of CXCR4 for
      different types of HIV-1 strains. By exchanging ECL2 residues between human and
      rat CXCR4, we found that several amino acid differences contributed to the
      inactivity of the rat CXCR4 toward HIV-189.6. In contrast, its inactivity toward
      HIV-1NDK seemed principally due to a serine at position 193 instead of to an
      aspartic acid (Asp193) in human CXCR4. Likewise, a mutation of Asp187 prevented
      usage of CXCR4 by FIVPET. Different mutations of Asp193, including its
      replacement by a glutamic acid, markedly reduced or suppressed the activity of
      CXCR4 for HIV-1NDK infection, indicating that the negative charge was not the
      only requirement. Mutations of Asp193 and of arginine residues (Arg183 and
      Arg188) of CXCR4 reduced the efficiency of HIV-1 infection for all HIV-1 strains
      tested. Other ECL2 mutations tested had strain-specific effects or no apparent
      effect on HIV-1 infection. The ECL2 mutants allowed us to identify residues
      contributing to the epitope of the 12G5 monoclonal antibody. Overall, residues
      with different charges and interspersed in ECL2 seem to participate in the
      coreceptor activity of CXCR4. This suggests that a conformational rather than
      linear epitope of ECL2 contributes to the HIV-1 binding site. However, certain
      HIV-1 and FIV strains seem to require the presence of a particular ECL2 residue.

PMID- 10074103
TI  - EBP2, a human protein that interacts with sequences of the Epstein-Barr virus
      nuclear antigen 1 important for plasmid maintenance.
AB  - The replication and stable maintenance of latent Epstein-Barr virus (EBV) DNA
      episomes in human cells requires only one viral protein, Epstein-Barr nuclear
      antigen 1 (EBNA1). To gain insight into the mechanisms by which EBNA1 functions,
      we used a yeast two-hybrid screen to detect human proteins that interact with
      EBNA1. We describe here the isolation of a protein, EBP2 (EBNA1 binding protein
      2), that specifically interacts with EBNA1. EBP2 was also shown to bind to DNA
      bound EBNA1 in a one-hybrid system, and the EBP2-EBNA1 interaction was confirmed
      by coimmunoprecipitation from insect cells expressing these two proteins. EBP2 is
      a 35-kDa protein that is conserved in a variety of organisms and is predicted to
      form coiled-coil interactions. We have mapped the region of EBNA1 that binds EBP2
      and generated internal deletion mutants of EBNA1 that are deficient in EBP2
      interactions. Functional analyses of these EBNA1 mutants show that the ability to
      bind EBP2 correlates with the ability of EBNA1 to support the long-term
      maintenance in human cells of a plasmid containing the EBV origin, oriP. An EBNA1
      mutant lacking amino acids 325 to 376 was defective for EBP2 binding and long
      term oriP plasmid maintenance but supported the transient replication of oriP
      plasmids at wild-type levels. Thus, our results suggest that the EBNA1-EBP2
      interaction is important for the stable segregation of EBV episomes during cell
      division but not for the replication of the episomes.

PMID- 10074104
TI  - Differential cell tropism of feline immunodeficiency virus molecular clones in
      vivo.
AB  - Independent studies have demonstrated different cell tropisms for molecular
      clones of feline immunodeficiency virus (FIV). In this report, we examined three
      clones, FIV-pF34, FIV-14, and FIV-pPPR, for replication in Crandell feline kidney
      (CrFK) cells, feline peripheral blood mononuclear cells (PBMC), and feline
      macrophage cultures. Importantly, cell tropism for these three clones was also
      examined in vivo. FIV-pF34 replication was efficient in CrFK cells but severely
      restricted in PBMC, whereas replication of FIV-pPPR was vigorous in PBMC but
      severely restricted in CrFK cells. FIV-14 replication was productive in both CrFK
      cells and PBMC. Interestingly, all three molecular clones replicated with similar
      efficiencies in primary feline monocyte-derived macrophages. In vivo, FIV-pF34
      proved least efficient for establishing persistent infection, and proviral DNA
      when detectable, was localized predominately to nonlymphoid cell populations
      (macrophages). FIV-pPPR proved most efficient for induction of a persistent
      viremia in vivo, and proviral DNA was localized predominately in CD4(+) and
      CD8(+) lymphocyte subsets. FIV-14 inoculation of cats resulted in an infection
      characterized by seroconversion and localization of proviral DNA in CD4(+)
      lymphocytes only. Results of this study on diverse FIV molecular clones revealed
      that in vitro replication efficiency of an FIV isolate in PBMC directly
      correlated with replication efficiency in vivo, whereas proficiency for
      replication in macrophages in vitro was not predictive for replication potential
      in vivo. Also, infection of both CD4(+) and CD8(+) lymphocyte subsets was
      associated with higher virus load in vivo. Results of the studies on these three
      FIV clones, which exhibited differential cell tropism, indicated a correlation
      between in vitro and in vivo cell tropism and virus replication.

PMID- 10074105
TI  - Opposing effects of human immunodeficiency virus type 1 matrix mutations support
      a myristyl switch model of gag membrane targeting.
AB  - Targeting of the human immunodeficiency virus type 1 (HIV-1) Gag precursor
      Pr55(gag) to the plasma membrane, the site of virus assembly, is primarily
      mediated by the N-terminal matrix (MA) domain. N-myristylation of MA is essential
      for the stable association of Pr55(gag) with membranes and for virus assembly. We
      now show that single amino acid substitutions near the N terminus of MA can
      dramatically impair assembly without compromising myristylation. Subcellular
      fractionation demonstrated that Gag membrane binding was compromised to a similar
      extent as in the absence of the myristyl acceptor site, indicating that the
      myristyl group was not available for membrane insertion. Remarkably, the effects
      of the N-terminal modifications could be completely suppressed by second-site
      mutations in the globular core of MA. The compensatory mutations enhanced Gag
      membrane binding and increased viral particle yields above wild-type levels,
      consistent with an increase in the exposure of the myristyl group. Our results
      support a model in which the compact globular core of MA sequesters the myristyl
      group to prevent aberrant binding to intracellular membranes, while the N
      terminus is critical to allow the controlled exposure of the myristyl group for
      insertion into the plasma membrane.

PMID- 10074106
TI  - Foamy virus capsids require the cognate envelope protein for particle export.
AB  - Unlike other subclasses of the Retroviridae the Spumavirinae, its prototype
      member being the so-called human foamy virus (HFV), require the expression of the
      envelope (Env) glycoprotein for viral particle egress. Both the murine leukemia
      virus (MuLV) Env and the vesicular stomatitis virus G protein, which efficiently
      pseudotype other retrovirus capsids, were not able to support export of HFV
      particles. Analysis of deletion and point mutants of the HFV Env protein revealed
      that the HFV Env cytoplasmic domain (CyD) is dispensable for HFV particle
      envelopment, release, and infectivity, whereas deletion of the membrane-spanning
      domain (MSD) led to an accumulation of naked capsids in the cytoplasm. Neither
      alternative membrane association of HFV Env deletion mutants lacking the MSD and
      CyD via phosphoglycolipid anchor nor domain swapping mutants, with the MSD or CyD
      of MuLV Env and VSV-G exchanged against the corresponding HFV domains, could
      restore particle envelopment and the release defect of pseudotypes. However,
      replacement of the HFV MSD with that of MuLV led to budding of HFV capsids at the
      intracellular membranes. These virions were of apparently wild-type morphology
      but were not naturally released into the supernatant and they were noninfectious.

PMID- 10074107
TI  - A brome mosaic virus intergenic RNA3 replication signal functions with viral
      replication protein 1a to dramatically stabilize RNA in vivo.
AB  - Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like
      superfamily, encodes two RNA replication proteins. The 1a protein has putative
      helicase and RNA-capping domains, whereas 2a contains a polymerase-like domain.
      Saccharomyces cerevisiae expressing 1a and 2a is capable of replicating a BMV
      RNA3 template produced by in vivo transcription of a DNA copy of RNA3. Although
      insufficient for RNA3 replication, the expression of 1a protein alone results in
      a dramatic and specific stabilization of the RNA3 template in yeast. As one step
      toward understanding 1a-induced stabilization of RNA3, the interactions involved,
      and its possible relation to RNA replication, we have identified the cis-acting
      sequences required for this effect. We find that 1a-induced stabilization is
      mediated by a 150- to 190-base segment of the RNA3 intergenic region
      corresponding to a previously identified enhancer of RNA3 replication. Moreover,
      this segment is sufficient to confer 1a-induced stability on a heterologous beta
      globin RNA. Within this intergenic segment, partial deletions that inhibited 1a
      induced stabilization in yeast expressing 1a alone resulted in parallel decreases
      in the levels of negative- and positive-strand RNA3 replication products in yeast
      expressing 1a and 2a. In particular, a small deletion encompassing a motif
      corresponding to the box B element of RNA polymerase III promoters dramatically
      reduced the ability of RNAs to respond to 1a or 1a and 2a. These and other
      findings suggest that 1a-induced stabilization likely reflects an early template
      selection step in BMV RNA replication.

PMID- 10074108
TI  - Isolation from tobacco mosaic virus-infected tobacco of a solubilized template
      specific RNA-dependent RNA polymerase containing a 126K/183K protein heterodimer.
AB  - The complete nucleotide sequence was determined for the putative RNA polymerase
      (183K protein) gene of tobacco mosaic virus (TMV) OM strain, which differed from
      the related strain, vulgare, by 51 positions in its nucleotide sequence and 6
      residues in its amino acid sequence. Three segments of this 183K protein, each
      containing the sequence motif of methyltransferase (M), helicase (H), or RNA
      dependent RNA polymerase (P), were expressed in Escherichia coli as fusion
      proteins with hexahistidine tags, and domain-specific antibodies were raised
      against purified His-tagged M and P polypeptides. By immunoaffinity purification,
      a template-specific RNA-dependent RNA polymerase containing a heterodimer of the
      full-length 183K and 126K (an amino-terminal-proximal portion of the 183K
      protein) viral proteins was isolated. We propose that the TMV RNA polymerase for
      minus-strand RNA synthesis is composed of one molecule each of the 183- and 126
      kDa proteins, possibly together with two or more host proteins.

PMID- 10074109
TI  - The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for
      static retention in the endoplasmic reticulum.
AB  - Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a noncovalent
      heterodimer which, in the cell, accumulates in the endoplasmic reticulum (ER).
      Contrary to what is observed for proteins with a KDEL or a KKXX ER-targeting
      signal, the ER localization of the HCV glycoprotein complex is due to a static
      retention in this compartment rather than to its retrieval from the cis-Golgi
      region. A static retention in the ER is also observed when E2 is expressed in the
      absence of E1 or for a chimeric protein containing the ectodomain of CD4 in
      fusion with the transmembrane domain (TMD) of E2. Although they do not exclude
      the presence of an intracellular localization signal in E1, these data do suggest
      that the TMD of E2 is an ER retention signal for HCV glycoprotein complex. In
      this study chimeric proteins containing the ectodomain of CD4 or CD8 fused to the
      C-terminal hydrophobic sequence of E1 were shown to be localized in the ER,
      indicating that the TMD of E1 is also a signal for ER localization. In addition,
      these chimeric proteins were not processed by Golgi enzymes, indicating that the
      TMD of E1 is responsible for true retention in the ER, without recycling through
      the Golgi apparatus. Together, these data suggest that at least two signals (TMDs
      of E1 and E2) are involved in ER retention of the HCV glycoprotein complex.

PMID- 10074110
TI  - Bacterial lipopolysaccharide inhibits dengue virus infection of primary human
      monocytes/macrophages by blockade of virus entry via a CD14-dependent mechanism.
AB  - Monocytes/macrophages (MO/Mphi) are the major target cells for both dengue virus
      (DV) and bacterial lipopolysaccharide (LPS), and the aim of this study was to
      define their interactions. We had found that LPS markedly suppressed DV infection
      of primary human MO/Mphi when it was added to cultures prior to or together with,
      but not after, viral adsorption. The inhibitory effect of LPS was direct and
      specific and was not mediated by LPS-induced secretion of cytokines and
      chemokines such as tumor necrosis factor alpha, interleukin-1beta (IL-1beta), IL
      6, IL-8, IL-12, alpha interferon, MIP-1alpha, and RANTES. In fact, productive DV
      infection was not blocked but was just postponed by LPS, with a time lag equal to
      one viral replication cycle. Time course studies demonstrated that LPS was only
      effective in suppressing DV infection of MO/Mphi that had not been previously
      exposed to the virus. At various time points after viral adsorption, the level of
      unbound viruses that remained free in the culture supernatants of LPS-pretreated
      cultures was much higher than that of untreated controls. These observations
      suggest that the LPS-induced suppression of DV replication was at the level of
      virus attachment and/or entry. Blockade of the major LPS receptor, CD14, with
      monoclonal antibodies MY4 or MoS39 failed to inhibit DV infection but could
      totally abrogate the inhibitory effect of LPS. Moreover, human serum could
      significantly enhance the LPS-induced DV suppression in a CD14-dependent manner,
      indicating that the "binding" of LPS to CD14 was critical for the induction of
      virus inhibition. Taken together, our results suggest that LPS blocked DV entry
      into human MO/Mphi via its receptor CD14 and that a CD14-associated cell surface
      structure may be essential for the initiation of a DV infection.

PMID- 10074111
TI  - Expression of murine coronavirus recombinant papain-like proteinase: efficient
      cleavage is dependent on the lengths of both the substrate and the proteinase
      polypeptides.
AB  - Proteolytic processing of the replicase gene product of mouse hepatitis virus
      (MHV) is essential for viral replication. In MHV strain A59 (MHV-A59), the
      replicase gene encodes two predicted papain-like proteinase (PLP) domains, PLP-1
      and PLP-2. Previous work using viral polypeptide substrates synthesized by in
      vitro transcription and translation from the replicase gene demonstrated both cis
      and trans cleavage activities for PLP-1. We have cloned and overexpressed the PLP
      1 domain in Escherichia coli by using a T7 RNA polymerase promoter system or as a
      maltose-binding protein (MBP) fusion protein. With both overexpression systems,
      the recombinant PLP-1 exhibited trans cleavage activity when incubated with in
      vitro-synthesized viral polypeptide substrates. Subsequent characterization of
      the recombinant PLP-1 revealed that in vitro trans cleavage is more efficient at
      22 degrees C than at higher temperatures. Using substrates of increasing lengths,
      we observed efficient cleavage by PLP-1 requires a substrate greater than 69 kDa.
      In addition, when PLP-1 was expressed as a polypeptide that included additional
      viral sequences at the carboxyl terminus of the predicted PLP-1 domain, a
      fivefold increase in proteolytic activity was observed. The data presented here
      support previous data suggesting that in vitro and in vivo cleavage of the ORF 1a
      polyprotein by PLP-1 can occur in both in cis and in trans. In contrast to the
      cleavage activity demonstrated for PLP-1, no in vitro cleavage in cis or in trans
      could be detected with PLP-2 expressed either as a polypeptide, including
      flanking viral sequences, or as an MBP fusion enzyme.

PMID- 10074112
TI  - Vif and the p55(Gag) polyprotein of human immunodeficiency virus type 1 are
      present in colocalizing membrane-free cytoplasmic complexes.
AB  - The Vif protein of human immunodeficiency virus type 1 (HIV-1) is a potent
      regulator of viral infectivity. Current data posit that Vif functions late in
      replication to modulate assembly, budding, and/or maturation. Consistent with
      this model, earlier indirect immunofluorescence analyses of HIV-1-infected cells
      demonstrated that Vif and Gag colocalize to a substantial degree (J. H. M. Simon,
      R. A. M. Fouchier, T. E. Southerling, C. B. Guerra, C. K. Grant, and M. H. Malim,
      J. Virol. 71:5259-5267, 1997). Here, we describe a series of subcellular
      fractionation studies which indicate that Vif and the p55(Gag) polyprotein are
      present in membrane-free cytoplasmic complexes that copurify in sucrose density
      gradients and are stable in nonionic detergents. Both Vif and Gag are targeted to
      these complexes independent of each other, and their association with them
      appears to be mediated by protein-protein interactions. We propose that these
      complexes may represent viral assembly intermediates and that Vif is
      appropriately localized to influence the final stages of the viral life cycle
      and, therefore, the infectivity of progeny virions.

PMID- 10074113
TI  - Mutational analysis of the human immunodeficiency virus type 1 Vif protein.
AB  - Lentivirus Vif proteins are potent regulators of virus infectivity. However,
      relatively little is known about the functional domains, peptide motifs, or
      residues of any Vif protein. In this report, we present the first extensive
      mutagenesis analysis of the 192-amino-acid human immunodeficiency virus type 1
      (HIV-1) Vif protein. A large number of scanning missense (mostly alanine
      substitution) and deletion mutations were introduced into the HIV-1HXB3 vif gene,
      and the resulting proteins were evaluated for the induction of virus infectivity
      as well as subcellular localization. The results show that amino acids dispersed
      throughout Vif's linear sequence are important for function. However, because
      many of the inactive proteins also appear to be mislocalized, we suggest that
      many of them may actually be misfolded rather lacking an intracellular targeting
      signal. Interestingly, disruptions within an internal region spanning residues
      114 to 146 give rise to mutant proteins that either retain function or are
      inactive but are not substantially mislocalized. We therefore speculate that this
      region, which harbors two essential cysteine residues and one essential serine
      residue, may contain aspects of a putative Vif effector domain.

PMID- 10074114
TI  - Charged-to-alanine scanning mutagenesis of the N-terminal half of adeno
      associated virus type 2 Rep78 protein.
AB  - The adeno-associated virus (AAV) Rep78 and Rep68 proteins are required for site
      specific integration of the AAV genome into the AAVS1 locus (19q13.3-qter) as
      well as for viral DNA replication. Rep78 and Rep68 bind to the GAGC motif on the
      inverted terminal repeat (ITR) and cut at the trs (terminal resolution site). A
      similar reaction is believed to occur in AAVS1 harboring an analogous GAGC motif
      and a trs homolog, followed by integration of the AAV genome. To elucidate the
      functional domains of Rep proteins at the amino acid level, we performed charged
      to-alanine scanning mutagenesis of the N terminus (residues 1 to 240) of Rep78,
      where DNA binding and nicking domains are thought to exist. Mutants were analyzed
      for their abilities to bind the GAGC motif, nick at the trs homolog, and
      integrate an ITR-containing plasmid into AAVS1 by electrophoretic mobility shift
      assay, trs endonuclease assay, and PCR-based integration assay. We identified the
      residues responsible for DNA binding: R107A, K136A, and R138A mutations
      completely abolished the binding activity. The H90A or H92A mutant, carrying a
      mutation in a putative metal binding site, lost nicking activity while retaining
      binding activity. Mutations affecting DNA binding or trs nicking also impaired
      the site-specific integration, except for E66A and E239A. These results provide
      important information on the structure-function relationship of Rep proteins. We
      also describe an aberrant nicking of Rep78. We found that Rep78 cuts
      predominantly at the trs homolog not only between the T residues (GGT/TGG), but
      also between the G and T residues (GG/TTGG), which may be influenced by the
      sequence surrounding the GAGC motif.

PMID- 10074115
TI  - IkappaB-mediated inhibition of virus-induced beta interferon transcription.
AB  - We have examined the consequences of overexpression of the IkappaBalpha and
      IkappaBbeta inhibitory proteins on the regulation of NF-kappaB-dependent beta
      interferon (IFN-beta) gene transcription in human cells after Sendai virus
      infection. In transient coexpression studies or in cell lines engineered to
      express different forms of IkappaB under tetracycline-inducible control, the IFN
      beta promoter (-281 to +19) linked to the chloramphenicol acetyltransferase
      reporter gene was differentially inhibited in response to virus infection.
      IkappaBalpha exhibited a strong inhibitory effect on virus-induced IFN-beta
      expression, whereas IkappaBbeta exerted an inhibitory effect only at a high
      concentration. Despite activation of the IkappaB kinase complex by Sendai virus
      infection, overexpression of the double-point-mutated (S32A/S36A) dominant
      repressors of IkappaBalpha (TD-IkappaBalpha) completely blocked IFN-beta gene
      activation by Sendai virus. Endogenous IFN-beta RNA production was also inhibited
      in Tet-inducible TD-IkappaBalpha-expressing cells. Inhibition of IFN-beta
      expression directly correlated with a reduction in the binding of NF-kappaB (p50
      RelA) complex to PRDII after Sendai virus infection in IkappaBalpha-expressing
      cells, whereas IFN-beta expression and NF-kappaB binding were only slightly
      reduced in IkappaBbeta-expressing cells. These experiments demonstrate a major
      role for IkappaBalpha in the regulation of NF-kappaB-induced IFN-beta gene
      activation and a minor role for IkappaBbeta in the activation process.

PMID- 10074116
TI  - Sufficient length of a poly(A) tail for the formation of a potential pseudoknot
      is required for efficient replication of bamboo mosaic potexvirus RNA.
AB  - RNAs transcribed from a full-length infectious cDNA clone of the bamboo mosaic
      potexvirus (strain O) genome, pBaMV-O, were infectious to Nicotiana benthamiana
      plants. Mutant genomes in which the poly(A) tail is absent or replaced by a 3'
      tRNA-like structure from turnip yellow mosaic virus RNA failed to amplify
      detectably in N. benthamiana protoplasts. No amplification was detected in
      protoplasts inoculated with transcripts containing 4, 7, or 10 adenylate residues
      at the 3' end, whereas transcript inocula with 15 adenylate residues resulted in
      coat protein accumulation to a level 26% of that resulting from inoculation with
      transcripts with 25 adenylate residues (designated as wild type). Coat protein
      accumulation levels of 69 and 98% relative to wild type were observed after
      inoculation of protoplasts with transcripts bearing poly(A) tails 18 and 22
      nucleotides long, respectively. The presence of a putative 3' pseudoknot
      structure including at least 13 adenylate residues of the 3'-terminal poly(A)
      tail was supported by enzymatic and chemical structural analysis. The functional
      relevance of this putative pseudoknot was tested by mutations that affected
      basepairing within the pseudoknot. These results support the existence of
      functional 3' pseudoknot that includes part of the 3' poly(A) tail.

PMID- 10074117
TI  - Mapping the genetic determinants of pathogenicity and plaque phenotype in swine
      vesicular disease virus.
AB  - A series of recombinant viruses were constructed using infectious cDNA clones of
      the virulent J1'73 (large plaque phenotype) and the avirulent H/3'76 (small
      plaque phenotype) strains of swine vesicular disease virus to identify the
      genetic determinants of pathogenicity and plaque phenotype. Both traits could be
      mapped to the region between nucleotides (nt) 2233 and 3368 corresponding to the
      C terminus of VP3, the whole of VP1, and the N terminus of 2A. In this region,
      there are eight nucleotide differences leading to amino acid changes between the
      J1'73 and the H/3'76 strains. Site-directed mutagenesis of individual nucleotides
      from the virulent to the avirulent genotype and vice versa indicated that A at nt
      2832, encoding glycine at VP1-132, and G at nt 3355, encoding arginine at 2APRO
      20, correlated with a large-plaque phenotype and virulence in pigs, irrespective
      of the origin of the remainder of the genome. Of these two sites, 2APRO-20
      appeared to be the dominant determinant for the large-plaque phenotype but
      further studies are required to elucidate their relative importance for virulence
      in pigs.

PMID- 10074118
TI  - Mutation of the YXXL endocytosis motif in the cytoplasmic tail of pseudorabies
      virus gE.
AB  - The role of alphaherpesvirus membrane protein internalization during the course
      of viral infection remains a matter of speculation. To determine the role of
      internalization of the pseudorabies virus (PRV) gE and gI proteins, we
      constructed viral mutants encoding specific mutations in the cytoplasmic tail of
      the gE gene that inhibited internalization of the gE-gI complex. We used these
      mutants to assess the role of gE-gI endocytosis in incorporation of the proteins
      into the viral envelope and in gE-mediated spread or gE-promoted virulence. In
      addition, we report that another viral mutant, PRV 25, which encodes a gE protein
      defective in endocytosis, contains an additional, previously uncharacterized
      mutation in the gE gene. We compared PRV 25 to another viral mutant, PRV 107,
      that does not express the cytoplasmic tail of the gE protein. The gE protein
      encoded by PRV 107 is also defective in endocytosis. We conclude that efficient
      endocytosis of gE is not required for gE incorporation into virions, gE-mediated
      virulence, or spread of virus in the rat central nervous system. However, we do
      correlate the defect in endocytosis to a small-plaque phenotype in cultured
      cells.

PMID- 10074119
TI  - Absence of internal ribosome entry site-mediated tissue specificity in the
      translation of a bicistronic transgene.
AB  - The 5' noncoding regions of the genomes of picornaviruses form a complex
      structure that directs cap-independent initiation of translation. This structure
      has been termed the internal ribosome entry site (IRES). The efficiency of
      translation initiation was shown, in vitro, to be influenced by the binding of
      cellular factors to the IRES. Hence, we hypothesized that the IRES might control
      picornavirus tropism. In order to test this possibility, we made a bicistronic
      construct in which translation of the luciferase gene is controlled by the IRES
      of Theiler's murine encephalomyelitis virus. In vitro, we observed that the IRES
      functions in various cell types and in macrophages, irrespective of their
      activation state. In vivo, we observed that the IRES is functional in different
      tissues of transgenic mice. Thus, it seems that the IRES is not an essential
      determinant of Theiler's virus tropism. On the other hand, the age of the mouse
      could be critical for IRES function. Indeed, the IRES was found to be more
      efficient in young mice. Picornavirus IRESs are becoming popular tools in
      transgenesis technology, since they allow the expression of two genes from the
      same transcription unit. Our results show that the Theiler's virus IRES is
      functional in cells of different origins and that it is thus a broad-spectrum
      tool. The possible age dependency of the IRES function, however, could be a
      drawback for gene expression in adult mice.

PMID- 10074120
TI  - Intranasal delivery of recombinant parvovirus-like particles elicits cytotoxic T
      cell and neutralizing antibody responses.
AB  - We previously demonstrated that chimeric porcine parvovirus-like particles
      (PPV:VLP) carrying heterologous epitopes, when injected intraperitoneally into
      mice without adjuvant, activate strong CD4(+) and CD8(+) T-cell responses
      specific for the foreign epitopes. In the present study, we investigated the
      immunogenicity of PPV:VLP carrying a CD8(+) T-cell epitope from the lymphocytic
      choriomeningitis virus (LCMV) administered by mucosal routes. Mice immunized
      intranasally with recombinant PPV:VLP, in the absence of adjuvant, developed high
      levels of PPV-specific immunoglobulin G (IgG) and/or IgA in their serum, as well
      as in mucosal sites such as the bronchoalveolar and intestinal fluids. Antibodies
      in sera from mice immunized parenterally or intranasally with PPV:VLP were
      strongly neutralizing in vitro. Intranasal immunization with PPV:VLP carrying the
      LCMV CD8(+) T-cell epitope also elicited a strong peptide-specific cytotoxic-T
      cell (CTL) response. In contrast, mice orally immunized with recombinant PPV:VLP
      did not develop any antibody or CTL responses. We also showed that mice primed
      with PPV:VLP are still able to develop strong CTL responses after subsequent
      immunization with chimeric PPV:VLP carrying a foreign CD8(+) T-cell epitope.
      These results highlight the attractive potential of PPV:VLP as a safe,
      nonreplicating antigen carrier to stimulate systemic and mucosal immunity after
      nasal administration.

PMID- 10074121
TI  - Drastic fitness loss in human immunodeficiency virus type 1 upon serial
      bottleneck events.
AB  - Muller's ratchet predicts fitness losses in small populations of asexual
      organisms because of the irreversible accumulation of deleterious mutations and
      genetic drift. This effect should be enhanced if population bottlenecks intervene
      and fixation of mutations is not compensated by recombination. To study whether
      Muller's ratchet could operate in a retrovirus, 10 biological clones were derived
      from a human immunodeficiency virus type 1 (HIV-1) field isolate by MT-4 plaque
      assay. Each clone was subjected to 15 plaque-to-plaque passages. Surprisingly,
      genetic deterioration of viral clones was very drastic, and only 4 of the 10
      initial clones were able to produce viable progeny after the serial plaque
      transfers. Two of the initial clones stopped forming plaques at passage 7, two
      others stopped at passage 13, and only four of the remaining six clones yielded
      infectious virus. Of these four, three displayed important fitness losses. Thus,
      despite virions carrying two copies of genomic RNA and the system displaying
      frequent recombination, HIV-1 manifested a drastic fitness loss as a result of an
      accentuation of Muller's ratchet effect.

PMID- 10074122
TI  - Identification of CXCR4 domains that support coreceptor and chemokine receptor
      functions.
AB  - The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its
      receptor CXCR4 is vital for cell trafficking during development, is capable of
      inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a
      coreceptor, and has been implicated in delaying disease progression to AIDS in
      vivo. Because of the importance of this chemokine-chemokine receptor pair to both
      development and disease, we investigated the molecular basis of the interaction
      between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and
      mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding
      and activates downstream signaling pathways by interacting with the second
      extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp
      Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin
      sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4
      mutants that were not capable of binding SDF-1 or signaling still supported HIV-1
      infection, indicating that the ability of CXCR4 to function as a coreceptor is
      independent of its ability to signal. Direct binding studies using the X4 gp120s
      HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and
      specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a
      conformationally complex structure on CXCR4. Several CXCR4 variants that did not
      support binding of soluble gp120 could still function as viral coreceptors,
      indicating that detectable binding of monomeric gp120 is not always predictive of
      coreceptor function.

PMID- 10074123
TI  - Detection and induction of equine infectious anemia virus-specific cytotoxic T
      lymphocyte responses by use of recombinant retroviral vectors.
AB  - Cytotoxic T lymphocytes (CTL) appear to be critical in resolving or reducing the
      severity of lentivirus infections. Retroviral vectors expressing the Gag/Pr or SU
      protein of the lentivirus equine infectious anemia virus (EIAV) were constructed
      and used to evaluate EIAV-specific CTL responses in horses. Three promoters,
      cytomegalovirus, simian virus SV40, and Moloney murine sarcoma virus (MoMSV) long
      terminal repeat (LTR), were used, and there was considerable variation in their
      ability to direct expression of Gag/Pr and SU. Vectors expressing EIAV proteins
      under the direction of MoMSV LTR and using the gibbon ape leukemia virus (GALV)
      Env for internalization were efficient at transducing equine kidney (EK) target
      cells and were effective targets for EIAV-specific CTL lysis. CTL from EIAV
      infected horses caused lysis of retroviral vector-transduced EK cells expressing
      either Gag/Pr or SU in an ELA-A-restricted manner. In contrast, lysis of
      recombinant vaccinia virus-infected EK cells expressing Gag/Pr and SU/TM was
      often non-LA-A restricted. Five horses were immunized by direct intramuscular
      injection with a mixture of retroviral vectors expressing Gag/Pr or SU, and one
      responded with EIAV-specific CTL. This result indicates that retroviral vector
      stimulation of CTL in horses needs to be optimized, perhaps by inclusion of
      appropriate cytokine genes in the constructs. However, the studies demonstrated
      that retroviral vector-transduced target cells were very effective for in vitro
      dissection of EIAV-specific CTL responses.

PMID- 10074124
TI  - Activated mouse Notch1 transactivates Epstein-Barr virus nuclear antigen 2
      regulated viral promoters.
AB  - Epstein-Barr virus nuclear antigen 2 (EBNA2) is essential for B-cell
      immortalization by EBV, most probably by its ability to transactivate a number of
      cellular and viral genes. EBNA2-responsive elements (EBNA2REs) have been
      identified in several EBNA2-regulated viral promoters, each of them carrying at
      least one RBP-Jkappa recognition site. RBP-Jkappa recruits EBNA2 to the EBNA2RE
      and, once complexed to EBNA2, is converted from a repressor into an activator. An
      activated form of the cellular receptor Notch also interacts with RBP-Jkappa,
      providing a link between EBNA2 and Notch signalling. To determine whether
      activated Notch is able to transactivate EBNA2-responsive viral promoters, we
      performed cotransfection experiments with activated mouse Notch1 (mNotch1-IC) and
      luciferase constructs of the BamHI C, LMP1, and LMP2A promoters. We present here
      evidence that mNotch1-IC transactivates viral promoters known to be regulated by
      EBNA2. As shown for EBNA2, mutations or deletions of the RBP-Jkappa sites
      diminish or eliminate mNotch1-IC-mediated transactivation of the promoters,
      pointing to an essential role for Notch-RBP-Jkappa interaction. In addition to
      RBP-Jkappa, other cellular factors may bind within the EBNA2REs of viral
      promoters. While some factors appear to play an important role in both EBNA2- and
      mNotch1-IC-mediated transactivation, others are only important for the activity
      of either EBNA2 or mNotch1-IC. We could observe specific mNotch1-IC-responsive
      regions, thereby throwing more light upon which cofactors interact with EBNA2 and
      mNotch1-IC, thus enabling them to become functionally transactivators in vivo.

PMID- 10074125
TI  - A second-site mutation that restores replication of a Tat-defective human
      immunodeficiency virus.
AB  - We previously constructed a large set of mutants of the human immunodeficiency
      virus type 1 (HIV-1) regulatory protein Tat with conservative amino acid
      substitutions in the activation domain. These Tat variants were analyzed in the
      context of the infectious virus, and several mutants were found to be defective
      for replication. In an attempt to obtain second-site suppressor mutations that
      could provide information on the Tat protein structure, some of the replication
      impaired viruses were used as a parent for the isolation of revertant viruses
      with improved replication capacity. Sequence analysis of revertant viruses
      frequently revealed changes within the tat gene, most often first-site reversions
      either to the wild-type amino acid or to related amino acids that restore, at
      least partially, the Tat function and virus replication. Of 30 revertant
      cultures, we identified only one second-site suppressor mutation. The inactive
      Y26A mutant yielded the second-site suppressor mutation Y47N that partially
      restored trans-activation activity and virus replication. Surprisingly, when the
      suppressor mutation was introduced in the wild-type Tat background, it also
      improved the trans-activation function of this protein about twofold. We conclude
      that the gain of function measured for the Y47N change is not specific for the
      Y26A mutant, arguing against a direct interaction of Tat amino acids 26 and 47 in
      the three-dimensional fold of this protein. Other revertant viruses did not
      contain any additional Tat changes, and some viruses revealed putative second
      site Tat mutations that did not significantly improve Tat function and virus
      replication. We reason that these mutations were introduced by chance through
      founder effects or by linkage to suppressor mutations elsewhere in the virus
      genome. In conclusion, the forced evolution of mutant HIV-1 genomes, which is an
      efficient approach for the analysis of RNA regulatory motifs, seems less suited
      for the analysis of the structure of this small transcription factor, although
      protein variants with interesting properties can be generated.

PMID- 10074126
TI  - Effect of the attenuating deletion and of sequence alterations evolving in vivo
      on simian immunodeficiency virus C8-Nef function.
AB  - The simian immunodeficiency virus macC8 (SIVmacC8) variant has been used in a
      European Community Concerted Action project to study the efficacy and safety of
      live attenuated SIV vaccines in a large number of macaques. The attenuating
      deletion in the SIVmacC8 nef-long terminal repeat region encompasses only 12 bp
      and is "repaired" in a subset of infected animals. It is unknown whether C8-Nef
      retains some activity. Since it seems important to use only well-characterized
      deletion mutants in live attenuated vaccine studies, we analyzed the relevance of
      the deletion, and the duplications and point mutations selected in infected
      macaques for Nef function in vitro. The deletion, affecting amino acids 143 to
      146 (DMYL), resulted in a dramatic decrease in Nef stability and function. The
      initial 12-bp duplication resulted in efficient Nef expression and an
      intermediate phenotype in infectivity assays, but it did not significantly
      restore the ability of Nef to stimulate viral replication and to downmodulate CD4
      and class I major histocompatibility complex cell surface expression. The
      additional substitutions however, which subsequently evolved in vivo, gradually
      restored these Nef functions. It was noteworthy that coinfection experiments in
      the T-lymphoid 221 cell line revealed that even SIVmac nef variants carrying the
      original 12-bp deletion readily outgrew an otherwise isogenic virus containing a
      182-bp deletion in the nef gene. Thus, although C8-Nef is unstable and severely
      impaired in in vitro assays, it maintains some residual activity to stimulate
      viral replication.

PMID- 10074127
TI  - A single amino acid in the adenovirus type 37 fiber confers binding to human
      conjunctival cells.
AB  - A 46-kDa receptor, coxsackievirus-adenovirus (Ad) receptor (CAR), mediates cell
      attachment of a number of different Ad serotypes; however, not all Ad serotypes
      utilize this receptor for infection. Moreover, the precise amino acid sequences
      in the Ad fiber protein that mediate cell attachment have yet to be identified.
      We investigated the interaction of subgroup D Ads with human ocular cells. Ad
      serotype 37 (Ad37), a virus associated with epidemic keratoconjunctivitis, but
      not a closely related virus serotype, Ad19p, exhibited preferential binding to
      and infection of human conjunctival cells. A single amino acid substitution in
      the Ad19p fiber distal domain (knob), Glu240 to Lys, conferred binding to
      conjunctival cells, while the reverse substitution in the Ad37 fiber abrogated
      cell binding. These findings provide new information on the fiber sequences that
      regulate Ad host cell tropism.

PMID- 10074128
TI  - The herpes simplex virus type 1 regulatory protein ICP27 is required for the
      prevention of apoptosis in infected human cells.
AB  - The herpes simplex virus type 1 (HSV-1) ICP27 protein is an immediate-early or
      alpha protein which is essential for the optimal expression of late genes as well
      as the synthesis of viral DNA in cultures of Vero cells. Our specific goal was to
      characterize the replication of a virus incapable of synthesizing ICP27 in
      cultured human cells. We found that infection with an HSV-1 ICP27 deletion virus
      of at least three separate strains of human cells did not produce immediate-early
      or late proteins at the levels observed following wild-type virus infections.
      Cell morphology, chromatin condensation, and genomic DNA fragmentation
      measurements demonstrated that the human cells died by apoptosis after infection
      with the ICP27 deletion virus. These features of the apoptosis were identical to
      those which occur during wild-type infections of human cells when total protein
      synthesis has been inhibited. Vero cells infected with the ICP27 deletion virus
      did not exhibit any of the features of apoptosis. Based on these results, we
      conclude that while HSV-1 infection likely induced apoptosis in all cells, viral
      evasion of the response differed among the cells tested in this study.

PMID- 10074129
TI  - Theiler's viruses with mutations in loop I of VP1 lead to altered tropism and
      pathogenesis.
AB  - Theiler's murine encephalomyelitis viruses are picornaviruses that can infect the
      central nervous system. The DA strain produces an acute polioencephalomyelitis
      followed by a chronic demyelinating disease in its natural host, the mouse. The
      ability of DA virus to induce a demyelinating disease renders this virus
      infection a model for human demyelinating diseases such as multiple sclerosis.
      Here we describe the generation and characterization of DA virus mutants that
      contain specific mutations in the viral capsid protein VP1 at sites believed to
      be important contact regions for the cellular receptor(s). A mutant virus with a
      threonine-to-aspartate (T81D) substitution in VP1 loop I adjacent to the putative
      virus receptor binding site exhibited a large-plaque phenotype but had a slower
      replication cycle in vitro. When this mutant virus was injected into susceptible
      mice, an altered tropism was seen during the acute stage of the disease and the
      chronic demyelinating disease was not produced. A virus with a threonine-to
      valine substitution (T81V) did not cause any changes in the pattern or extent of
      disease seen in mice, whereas a virus with a tryptophan substitution at this
      position (T81W) produced a similar acute disease but was attenuated for the
      development of the chronic disease. A change in amino acids in a hydrophobic
      patch located in the wall of the pit, VP1 position 91, to a hydrophilic threonine
      (V91T) resulted in a profound attenuation of the acute and chronic disease
      without persistence of virus. This report illustrates the importance of the loop
      I of VP1 and a site in the wall of the pit in pathogenesis and that amino acid
      substitutions at these sites result in altered virus-host interactions.

PMID- 10074130
TI  - Effects of human cytomegalovirus major immediate-early proteins in controlling
      the cell cycle and inhibiting apoptosis: studies with ts13 cells.
AB  - The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) encodes
      several MIE proteins (MIEPs) produced as a result of alternative splicing and
      polyadenylation of the primary transcript. Previously we demonstrated that the
      HCMV MIEPs expressed from the entire MIE gene could rescue the temperature
      sensitive (ts) transcriptional defect in the ts13 cell line. This defect is
      caused by a ts mutation in TAFII250, the 250-kDa TATA binding protein-associated
      factor (TAF). These and other data suggested that the MIEPs perform a TAF-like
      function in complex with the basal transcription factor TFIID. In addition to the
      transcriptional defect, the ts mutation in ts13 cells results in a defect in cell
      cycle progression which ultimately leads to apoptosis. Since all of these defects
      can be rescued by wild-type TAFII250, we asked whether the MIEPs could rescue the
      cell cycle defect and/or affect the progression to apoptosis. We have found that
      the MIEPs, expressed from the entire MIE gene, do not rescue the cell cycle block
      in ts13 cells grown at the nonpermissive temperature. However, despite the
      maintenance of the cell cycle block, the ts13 cells which express the MIEPs are
      resistant to apoptosis. MIEP mutants, which have previously been shown to be
      defective in rescuing the ts transcriptional defect, maintained the ability to
      inhibit apoptosis. Hence, the MIEP functions which affect transcription appear to
      be separable from the functions which inhibit apoptosis. We discuss these data in
      the light of the HCMV life cycle and the possibility that the MIEPs promote
      cellular transformation by a "hit-and-run" mechanism.

PMID- 10074131
TI  - Lentivirus vectors using human and simian immunodeficiency virus elements.
AB  - Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1)
      constitute a recent development in the field of gene therapy. A key property of
      HIV-1-derived vectors is their ability to infect nondividing cells. Although high
      titer HIV-1-derived vectors have been produced, concerns regarding safety still
      exist. Safety concerns arise mainly from the possibility of recombination between
      transfer and packaging vectors, which may give rise to replication-competent
      viruses with pathogenic potential. We describe a novel lentivirus vector which is
      based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus
      (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived
      genome is encapsidated by SIVmac core particles. These core particles are
      pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV
      1 and SIVmac is low, the likelihood of recombination between vector elements
      should be reduced. In addition, the packaging construct (SIVpack) for this
      lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus,
      the potential for pathogenicity with this vector system is minimal. The
      transduction ability of HIV/SIVpack/G was demonstrated with immortalized human
      lymphocytes, human primary macrophages, human bone marrow-derived CD34(+) cells,
      and primary mouse neurons. To our knowledge, these experiments constitute the
      first demonstration that the HIV-1-derived genome can be packaged by an SIVmac
      capsid. We demonstrate that the lentivirus vector described here recapitulates
      the biological properties of HIV-1-derived vectors, although with increased
      potential for safety in humans.

PMID- 10074132
TI  - Hepatitis C virus core protein interacts with cellular putative RNA helicase.
AB  - The nucleocapsid core protein of hepatitis C virus (HCV) has been shown to trans
      act on several viral or cellular promoters. To get insight into the trans-action
      mechanism of HCV core protein, a yeast two-hybrid cloning system was used for
      identification of core protein-interacting cellular protein. One such cDNA clone
      encoding the DEAD box family of putative RNA helicase was obtained. This cellular
      putative RNA helicase, designated CAP-Rf, exhibits more than 95% amino acid
      sequence identity to other known RNA helicases including human DBX and DBY, mouse
      mDEAD3, and PL10, a family of proteins generally involved in translation,
      splicing, development, or cell growth. In vitro binding or in vivo
      coimmunoprecipitation studies demonstrated the direct interaction of the full
      length/matured form and C-terminally truncated variants of HCV core protein with
      this targeted protein. Additionally, the protein's interaction domains were
      delineated at the N-terminal 40-amino-acid segment of the HCV core protein and
      the C-terminal tail of CAP-Rf, which encompassed its RNA-binding and ATP
      hydrolysis domains. Immunoblotting or indirect immunofluorescence analysis
      revealed that the endogenous CAP-Rf was mainly localized in the nucleus and to a
      lesser extent in the cytoplasm, and when fused with FLAG tag, it colocalized with
      the HCV core protein either in the cytoplasm or in the nucleus. Similar to other
      RNA helicases, this cellular RNA helicase has nucleoside triphosphatase
      deoxynucleoside triphosphatase activity, but this activity is inhibited by
      various forms of homopolynucleotides and enhanced by the HCV core protein.
      Moreover, transient expression of HCV core protein in human hepatoma HuH-7 cells
      significantly potentiated the trans-activation effect of FLAG-tagged CAP-Rf or
      untagged CAP-Rf on the luciferase reporter plasmid activity. All together, our
      results indicate that CAP-Rf is involved in regulation of gene expression and
      that HCV core protein promotes the trans-activation ability of CAP-Rf, likely via
      the complex formation and the modulation of the ATPase-dATPase activity of CAP
      Rf. These findings provide evidence that HCV may have evolved a distinct
      mechanism in alteration of host cellular gene expression regulation via the
      interaction of its nucleocapsid core protein and cellular putative RNA helicase
      known to participate in all aspects of cellular processes involving RNA
      metabolism. This feature of core protein may impart pleiotropic effects on host
      cells, which may partially account for its role in HCV pathogenesis.

PMID- 10074133
TI  - Adaptation of very virulent infectious bursal disease virus to chicken embryonic
      fibroblasts by site-directed mutagenesis of residues 279 and 284 of viral coat
      protein VP2.
AB  - The full-length RNA genomes of a chicken embryonic fibroblast (CEF)
      nonpermissive, very virulent infectious bursal disease virus (IBDV) (strain HK46)
      were amplified into cDNAs by reverse transcription-PCR. The full-length cDNAs
      were sequenced and subcloned into a eukaryotic expression vector, from which
      point mutations were introduced into the VP2 region by site-directed mutagenesis.
      The wild-type and mutated plasmids were transfected directly into CEFs to examine
      their ability to generate CEF-permissive recombinant viruses. Substitution of
      amino acid residues 279 (Asp-->Asn) and 284 (Ala-->Thr) of the VP2 protein
      yielded a recombinant virus which was able to be passaged in CEFs, whereas the
      wild-type cDNAs and an amino acid substitution at residue 330 (Ser-->Arg) of the
      VP2 protein alone did not yield viable virus. The results indicated that mutation
      of other viral proteins, including VP1, VP3, VP4, and VP5, was not required for
      CEF adaptation of the virus. The same approach may be used to produce CEF-adapted
      strains from newly evolved IBDVs or to manipulate the antigenicity of the virus.

PMID- 10074134
TI  - Interactions between vaccinia virus IEV membrane proteins and their roles in IEV
      assembly and actin tail formation.
AB  - The intracellular enveloped form of vaccinia virus (IEV) induces the formation of
      actin tails that are strikingly similar to those seen in Listeria and Shigella
      infections. In contrast to the case for Listeria and Shigella, the vaccinia virus
      protein(s) responsible for directly initiating actin tail formation remains
      obscure. However, previous studies with recombinant vaccinia virus strains have
      suggested that the IEV-specific proteins A33R, A34R, A36R, B5R, and F13L play an
      undefined role in actin tail formation. In this study we have sought to
      understand how these proteins, all of which are predicted to have small
      cytoplasmic domains, are involved in IEV assembly and actin tail formation. Our
      data reveal that while deletion of A34R, B5R, or F13L resulted in a severe
      reduction in IEV particle assembly, IEVs formed by the DeltaB5R and DeltaF13L
      deletion strains, but not DeltaA34R, were still able to induce actin tails. The
      DeltaA36R deletion strain produced normal amounts of IEV particles, although
      these were unable to induce actin tails. Using several different approaches, we
      demonstrated that A36R is a type Ib membrane protein with a large, 195-amino-acid
      cytoplasmic domain exposed on the surface of IEV particles. Finally,
      coimmunoprecipitation experiments demonstrated that A36R interacts with A33R and
      A34R but not with B5R and that B5R forms a complex with A34R but not with A33R or
      A36R. Using extracts from DeltaA34R- and DeltaA36R-infected cells, we found that
      the interaction of A36R with A33R and that of A34R with B5R are independent of
      A34R and A36R, respectively. We conclude from our observations that multiple
      interactions between IEV membrane proteins exist which have important
      implications for IEV assembly and actin tail formation. Furthermore, these data
      suggest that while A34R is involved in IEV assembly and organization, A36R is
      critical for actin tail formation.

PMID- 10074135
TI  - Primary and secondary structural elements required for synthesis of barley yellow
      dwarf virus subgenomic RNA1.
AB  - Barley yellow dwarf luteovirus (BYDV) generates three 3'-coterminal subgenomic
      RNAs (sgRNAs) in infected cells. The promoter of sgRNA1 is a putative hot spot
      for RNA recombination in luteovirus evolution. The sgRNA1 transcription start
      site was mapped previously to either nucleotide 2670 or nucleotide 2769 of BYDV
      genomic RNA (gRNA) in two independent studies. Our data support the former
      initiation site. The boundaries of the sgRNA1 promoter map between nucleotides
      2595 and 2692 on genomic RNA. Computer prediction, phylogenetic comparison, and
      structural probing revealed two stem-loops (SL1 and SL2) in the sgRNA1 promoter
      region on the negative strand. Promoter function was analyzed by inoculating
      protoplasts with a full-length infectious clone of the BYDV genome containing
      mutations in the sgRNA promoter. Because the promoter is located in an essential
      coding region of the replicase gene, we duplicated it in a nonessential part of
      the genome from which a new sgRNA was expressed. Mutational analysis revealed
      that secondary structure, but not the nucleotide sequence, was important at the
      base of SL1. Regions with both RNA primary and secondary structural features that
      contributed to transcription initiation were found at the top of SL1. Primary
      sequence, but not the secondary structure, was required in SL2, which includes
      the initiation site. Disruption of base pairing near the sgRNA1 start site
      increased the level of transcription three- to fourfold. We propose that both
      primary and secondary structures of the sgRNA1 promoter of BYDV play unique roles
      in sgRNA1 promoter recognition and transcription initiation.

PMID- 10074136
TI  - Woodchuck hepatitis virus posttranscriptional regulatory element enhances
      expression of transgenes delivered by retroviral vectors.
AB  - The expression of genes delivered by retroviral vectors is often inefficient, a
      potential obstacle for their widespread use in human gene therapy. Here, we
      explored the possibility that the posttranscriptional regulatory element of
      woodchuck hepatitis virus (WPRE) might help resolve this problem. Insertion of
      the WPRE in the 3' untranslated region of coding sequences carried by either
      oncoretroviral or lentiviral vectors substantially increased their levels of
      expression in a transgene-, promoter- and vector-independent manner. The WPRE
      thus increased either luciferase or green fluorescent protein production five- to
      eightfold, and effects of a comparable magnitude were observed with either the
      immediate-early cytomegalovirus or the herpesvirus thymidine kinase promoter and
      with both human immunodeficiency virus- and murine leukemia virus-based vectors.
      The WPRE exerted this influence only when placed in the sense orientation,
      consistent with its predicted posttranscriptional mechanism of action. These
      results demonstrate that the WPRE significantly improves the performance of
      retroviral vectors and emphasize that posttranscriptional regulation of gene
      expression should be taken into account in the design of gene delivery systems.

PMID- 10074137
TI  - The ski7 antiviral protein is an EF1-alpha homolog that blocks expression of non
      Poly(A) mRNA in Saccharomyces cerevisiae.
AB  - We mapped and cloned SKI7, a gene that negatively controls the copy number of L-A
      and M double-stranded RNA viruses in Saccharomyces cerevisiae. We found that it
      encodes a nonessential 747-residue protein with similarities to two translation
      factors, Hbs1p and EF1-alpha. The ski7 mutant was hypersensitive to hygromycin B,
      a result also suggesting a role in translation. The SKI7 product repressed the
      expression of nonpolyadenylated [non-poly(A)] mRNAs, whether capped or uncapped,
      thus explaining why Ski7p inhibits the propagation of the yeast viruses, whose
      mRNAs lack poly(A). The dependence of the Ski7p effect on 3' RNA structures
      motivated a study of the expression of capped non-poly(A) luciferase mRNAs
      containing 3' untranslated regions (3'UTRs) differing in length. In a wild-type
      strain, increasing the length of the 3'UTR increased luciferase expression due to
      both increased rates and duration of translation. Overexpression of Ski7p
      efficiently cured the satellite virus M2 due to a twofold-increased repression of
      non-poly(A) mRNA expression. Our experiments showed that Ski7p is part of the
      Ski2p-Ski3p-Ski8p antiviral system because a single ski7 mutation derepresses the
      expression of non-poly(A) mRNA as much as a quadruple ski2 ski3 ski7 ski8
      mutation, and the effect of the overexpression of Ski7p is not obtained unless
      other SKI genes are functional. ski1/xrn1Delta ski2Delta and ski1/xrn1Delta
      ski7Delta mutants were viable but temperature sensitive for growth.

PMID- 10074138
TI  - Interaction of the human immunodeficiency virus type 1 nucleocapsid with actin.
AB  - The nucleocapsid (NC) domain of the retrovirus Gag protein plays several
      important roles in the viral life cycle, including virus assembly, viral genomic
      RNA encapsidation, primer tRNA placement, and enhancement of viral reverse
      transcription. In this study, deletion of NC domain of human immunodeficiency
      virus type 1 (HIV-1) Gag was found to drastically reduce virus particle
      production in CD4(+) T cells. Cellular fractionation experiments showed that
      although most of the uncleaved wild-type HIV-1 Gag, unmyristylated Gag, and
      p6(Gag) domain-truncated Gag molecules copurified with the host cell
      cytoskeleton, most of the mutant Gag molecules lacking both the NC and p6(Gag)
      domains failed to cofractionate with cytoskeleton. In wild-type virus-infected
      cells, in which the viral protease was active, the cleaved NCp7 copurified with
      the cytoskeleton, whereas most of the MAp17 and CAp24 did not. Monoclonal
      antibody against actin coimmunoprecipitated full-length Gag and p6(Gag) domain
      truncated Gag molecules from cell lysates but failed to precipitate the truncated
      mutant Gag molecules lacking NC plus p6(Gag). Purified recombinant NCp7, but not
      CAp24, was able to bind F-actin in cosedimentation experiments. Furthermore, wild
      type NCp7 and a zinc finger mutant NCp7(F16A), like a cellular actin-binding
      protein (the villin headpiece), bound F-actin in a dose-dependent fashion in
      vitro. Taken together, these results suggest that HIV-1 NCp7 can bind F-actin
      directly and that interaction between HIV-1 Gag and the actin cytoskeleton
      through the NC domain may play an important role in HIV-1 assembly and/or other
      steps of the viral life cycle.

PMID- 10074139
TI  - RNA-Stimulated ATPase and RNA helicase activities and RNA binding domain of
      hepatitis G virus nonstructural protein 3.
AB  - Hepatitis G virus (HGV) nonstructural protein 3 (NS3) contains amino acid
      sequence motifs typical of ATPase and RNA helicase proteins. In order to examine
      the RNA helicase activity of the HGV NS3 protein, the NS3 region (amino acids 904
      to 1580) was fused with maltose-binding protein (MBP), and the fusion protein was
      expressed in Escherichia coli and purified with amylose resin and anion-exchange
      chromatography. The purified MBP-HGV/NS3 protein possessed RNA-stimulated ATPase
      and RNA helicase activities. Characterization of the ATPase and RNA helicase
      activities of MBP-HGV/NS3 showed that the optimal reaction conditions were
      similar to those of other Flaviviridae viral NS3 proteins. However, the kinetic
      analysis of NTPase activity showed that the MBP-HGV/NS3 protein had several
      unique properties compared to the other Flaviviridae NS3 proteins. The HGV NS3
      helicase unwinds RNA-RNA duplexes in a 3'-to-5' direction and can unwind RNA-DNA
      heteroduplexes and DNA-DNA duplexes as well. In a gel retardation assay, the MBP
      HGV/NS3 helicase bound to RNA, RNA/DNA, and DNA duplexes with 5' and 3' overhangs
      but not to blunt-ended RNA duplexes. We also found that the conserved motif VI
      was important for RNA binding. Further deletion mapping showed that the RNA
      binding domain was located between residues 1383 and 1395, QRRGRTGRGRSGR. Our
      data showed that the MBP-HCV/NS3 protein also contains the RNA binding domain in
      the similar domain.

PMID- 10074140
TI  - Gibbon ape leukemia virus receptor functions of type III phosphate transporters
      from CHOK1 cells are disrupted by two distinct mechanisms.
AB  - The Chinese hamster cell lines E36 and CHOK1 dramatically differ in
      susceptibility to amphotropic murine leukemia virus (A-MuLV) and gibbon ape
      leukemia virus (GALV); E36 cells are highly susceptible to both viruses, CHOK1
      cells are not. We have previously shown that GALV can infect E36 cells by using
      both its own receptor, HaPit1, and the A-MuLV receptor, HaPit2. Given that the
      two cell lines are from the same species, the loss of function of both of these
      receptors in CHOK1 cells is surprising. Other studies have shown that CHOK1 cells
      secrete proteins that block A-MuLV entry into CHOK1 as well as E36, suggesting
      the two A-MuLV receptors are functionally identical. However, CHOK1 conditioned
      medium does not block GALV entry into E36, indicating the secreted inhibitors do
      not block HaPit1. HaPit1 and ChoPit1 therefore differ as receptors for GALV;
      ChoPit1 is either inactivated by secreted factors or intrinsically nonfunctional.
      To determine why GALV cannot infect CHOK1, we cloned and sequenced ChoPit1 and
      ChoPit2. ChoPit2 is almost identical to HaPit2, which explains why CHOK1
      conditioned medium blocks A-MuLV entry via both receptors. Although ChoPit1 and
      HaPit1 are 91% identical, a notable difference is at position 550 in the fourth
      extracellular region, shown by several studies to be crucial for GALV infection.
      Pit1 and HaPit1 have aspartate at 550, whereas ChoPit1 has threonine at this
      position. We assessed the significance of this difference for GALV infection by
      replacing the aspartate 550 in Pit1 with threonine. This single substitution
      rendered Pit1 nonfunctional for GALV and suggests that threonine at 550
      inactivates ChoPit1 as a GALV receptor. Whether native ChoPit1 functions for GALV
      was determined by interference assays using Lec8, a glycosylation-deficient
      derivative of CHOK1 that is susceptible to both viruses and that has the same
      receptors as CHOK1. Unlike with E36, GALV and A-MuLV exhibited reciprocal
      interference when infecting Lec8, suggesting that they use the same receptor. We
      conclude both viruses can use ChoPit2 in the absence of the inhibitors secreted
      by CHOK1 and ChoPit1 is nonfunctional.

PMID- 10074141
TI  - A proline-rich motif within the matrix protein of vesicular stomatitis virus and
      rabies virus interacts with WW domains of cellular proteins: implications for
      viral budding.
AB  - The matrix (M) protein of rhabdoviruses has been shown to play a key role in
      virus assembly and budding; however, the precise mechanism by which M mediates
      these processes remains unclear. We have associated a highly conserved, proline
      rich motif (PPxY or PY motif, where P denotes proline, Y represents tyrosine, and
      x denotes any amino acid) of rhabdoviral M proteins with a possible role in
      budding mediated by the M protein. Point mutations that disrupt the PY motif of
      the M protein of vesicular stomatitis virus (VSV) have no obvious effect on
      membrane localization of M but instead lead to a decrease in the amount of M
      protein released from cells in a functional budding assay. Interestingly, the
      PPxY sequence within rhabdoviral M proteins is identical to that of the ligand
      which interacts with WW domains of cellular proteins. Indeed, results from two in
      vitro binding assays demonstrate that amino acids 17 through 33 and 29 through
      44, which contain the PY motifs of VSV and rabies virus M proteins, respectively,
      mediate interactions with WW domains of specific cellular proteins. Point
      mutations that disrupt the consensus PY motif of VSV or rabies virus M protein
      result in a significant decrease in their ability to interact with the WW
      domains. These properties of the PY motif of rhabdovirus M proteins are
      strikingly analogous to those of the late (L) budding domain identified in the
      gag-specific protein p2b of Rous sarcoma virus. Thus, it is possible that
      rhabdoviruses may usurp host proteins to facilitate the budding process and that
      late stages in the budding process of rhabdoviruses and retroviruses may have
      features in common.

PMID- 10074143
TI  - Acute hepatitis C virus structural gene sequences as predictors of persistent
      viremia: hypervariable region 1 as a decoy.
AB  - We hypothesized that hepatitis C virus (HCV) persistence is related to the
      sequence variability of putative envelope genes. This hypothesis was tested by
      characterizing quasispecies in specimens collected every six months from a cohort
      of acutely HCV-infected subjects (mean duration of specimen collection, 72 months
      after seroconversion). We evaluated 5 individuals who spontaneously cleared
      viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons
      that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1).
      To assess the quasispecies complexity and to detect variants for sequencing, the
      first PCR-positive sample was examined by using a previously described method
      that combines heteroduplex analysis and analysis of single-stranded
      conformational polymorphisms. The ratio of nonsynonymous to synonymous
      substitutions (dN/dS) within each sample was evaluated as an indicator of
      relative selective pressure. Amino acid sequences were analyzed for signature
      patterns, glycosylation signals, and charge. Quasispecies complexity was higher
      and E1 dN/dS ratios (selective pressure) were lower in those with persistent
      viremia; the association with persistence was strengthened by the presence of a
      combination of both characteristics. In contrast, a trend toward higher HVR1
      dN/dS ratios was detected among those with persistent viremia. We did not detect
      any such association for factors that may affect complexity such as serum HCV RNA
      concentration. HVR1 had a lower positive charge in subjects with persistent
      viremia, although no consistent motifs were detected. Our data suggest that HCV
      persistence is associated with a complex quasispecies and immune response to
      HVR1.

PMID- 10074142
TI  - Comparative characterization of rep proteins from the helper-dependent adeno
      associated virus type 2 and the autonomous goose parvovirus.
AB  - Adeno-associated viruses (AAVs) are nonautonomous human parvoviruses in that they
      are dependent on helper functions supplied by other viruses or on genotoxic
      stimuli for conditions permissive for replication. In the absence of helper, AAV
      type 2 enters latency by integration into a specific site on human chromosome 19.
      This feature of AAV, in combination with a lack of pathogenicity, makes AAV an
      attractive candidate vector for human gene therapy. Goose parvovirus (GPV) is
      both autonomous and pathogenic yet is highly homologous to AAV. To address the
      molecular bases for the different viral lifestyles, we compare the AAV and GPV
      nonstructural proteins, Rep78 and Rep1, respectively. We find that Rep78 and Rep1
      possess several biochemical activities in common, including (i) high-affinity DNA
      binding for sequences that constitute the minimal DNA replication origin; (ii)
      nucleoside triphosphate-dependent DNA helicase activity; and (iii) origin
      specific replication of double-stranded linear DNA. These experiments also
      establish a specific 38-bp DNA sequence as the minimal GPV DNA replication
      origin. It is noteworthy that although the proposed Rep binding sites of GPV and
      AAV are highly similar, Rep1 and Rep78 show a high degree of specificity for
      their respective origins, in both binding and replication assays. One significant
      difference was observed; with the minimal replication origin in adenovirus
      uninfected extracts, Rep78-mediated replication exhibited low processivity, as
      previously reported. In contrast, Rep1 efficiently replicated full-length
      template. Overall, our studies indicate that GPV Rep1 and AAV Rep78 support a
      comparable mode of replication. Thus, a comparison of the two proteins provides a
      model system with which to determine the contribution of Rep in the regulation of
      dependence and autonomy at the level of DNA replication.

PMID- 10074144
TI  - Early short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine treatment favorably
      alters the subsequent disease course in simian immunodeficiency virus-infected
      newborn Rhesus macaques.
AB  - Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful
      animal model of human pediatric AIDS to study disease pathogenesis and to develop
      intervention strategies aimed at delaying disease. In the present study, we
      demonstrate that very early events of infection greatly determine the ultimate
      disease course, as short-term antiviral drug administration during the initial
      viremia stage significantly delayed the onset of AIDS. Fourteen newborn macaques
      were inoculated orally with uncloned, highly virulent SIVmac251. The four
      untreated control animals showed persistently high virus levels and poor
      antiviral immune responses; they developed fatal immunodeficiency within 15
      weeks. In contrast, SIV-infected newborn macaques which were started on 9-[2-(R)
      (phosphonomethoxy)propyl]adenine (PMPA) treatment at 5 days of age and continued
      for either 14 or 60 days showed reduced virus levels and enhanced antiviral
      immune responses. This short-term PMPA treatment did not induce detectable
      emergence of SIV mutants with reduced in vitro susceptibility to PMPA. Although
      viremia increased in most animals after PMPA treatment was withdrawn, all animals
      remained disease-free for at least 6 months. Our data suggest that short-term
      treatment with a potent antiviral drug regimen during the initial viremia will
      significantly prolong AIDS-free survival for HIV-infected infants and adults.

PMID- 10074145
TI  - Human antibody responses to mature and immature forms of viral envelope in
      respiratory syncytial virus infection: significance for subunit vaccines.
AB  - A number of antibodies generated during human respiratory syncytial virus (RSV)
      infection have been cloned by the phage library approach. Antibodies reactive
      with an immunodominant epitope on the F glycoprotein of this virus have a high
      affinity for affinity-purified F antigen. These antibodies, however, have a much
      lower affinity for mature F glycoprotein on the surface of infected cells and are
      nonneutralizing. In contrast, a potent neutralizing antibody has a high affinity
      for mature F protein but a much lower affinity for purified F protein or F
      protein in viral lysates. The data indicate that at least two F protein
      immunogens are produced during natural RSV infection: immature F, found in viral
      lysates, and mature F, found on infected cells or virions. Binding studies with
      polyclonal human immunoglobulin G suggest that the antibody responses to the two
      immunogens are of similar magnitudes. Competitive binding studies suggest that
      overlap between the responses is relatively limited. A mature envelope with an
      antigenic configuration different from that of the immature envelope has an
      evolutionary advantage in that the infecting virus is less subject to
      neutralization by the humoral response to the immature envelope that inevitably
      arises following lysis of infected cells. Subunit vaccines may be at a
      disadvantage because they most often resemble immature envelope molecules and
      ignore this aspect of viral evasion.

PMID- 10074146
TI  - Reovirus virion-like particles obtained by recoating infectious subvirion
      particles with baculovirus-expressed sigma3 protein: an approach for analyzing
      sigma3 functions during virus entry.
AB  - Structure-function studies with mammalian reoviruses have been limited by the
      lack of a reverse-genetic system for engineering mutations into the viral genome.
      To circumvent this limitation in a partial way for the major outer-capsid protein
      sigma3, we obtained in vitro assembly of large numbers of virion-like particles
      by binding baculovirus-expressed sigma3 protein to infectious subvirion particles
      (ISVPs) that lack sigma3. A level of sigma3 binding approaching 100% of that in
      native virions was routinely achieved. The sigma3 coat in these recoated ISVPs
      (rcISVPs) appeared very similar to that in virions by electron microscopy and
      three-dimensional image reconstruction. rcISVPs retained full infectivity in
      murine L cells, allowing their use to study sigma3 functions in virus entry. Upon
      infection, rcISVPs behaved identically to virions in showing an extended lag
      phase prior to exponential growth and in being inhibited from entering cells by
      either the weak base NH4Cl or the cysteine proteinase inhibitor E-64. rcISVPs
      also mimicked virions in being incapable of in vitro activation to mediate lysis
      of erythrocytes and transcription of the viral mRNAs. Last, rcISVPs behaved like
      virions in showing minor loss of infectivity at 52 degrees C. Since rcISVPs
      contain virion-like levels of sigma3 but contain outer-capsid protein mu1/mu1C
      mostly cleaved at the delta-phi junction as in ISVPs, the fact that rcISVPs
      behaved like virions (and not ISVPs) in all of the assays that we performed
      suggests that sigma3, and not the delta-phi cleavage of mu1/mu1C, determines the
      observed differences in behavior between virions and ISVPs. To demonstrate the
      applicability of rcISVPs for genetic studies of protein functions in reovirus
      entry (an approach that we call recoating genetics), we used chimeric sigma3
      proteins to localize the primary determinants of a strain-dependent difference in
      sigma3 cleavage rate to a carboxy-terminal region of the ISVP-bound protein.

PMID- 10074147
TI  - Genetic evidence that EBNA-1 is needed for efficient, stable latent infection by
      Epstein-Barr virus.
AB  - Replication and maintenance of the 170-kb circular chromosome of Epstein-Barr
      virus (EBV) during latent infection are generally believed to depend upon a
      single viral gene product, the nuclear protein EBNA-1. EBNA-1 binds to two
      clusters of sites at oriP, an 1, 800-bp sequence on the EBV genome which can
      support replication and maintenance of artificial plasmids introduced into cell
      lines that contain EBNA-1. To investigate the importance of EBNA-1 to latent
      infection by EBV, we introduced a frameshift mutation into the EBNA-1 gene of EBV
      by recombination along with a flanking selectable marker. EBV genomes carrying
      the frameshift mutation could be isolated readily after superinfecting EBV
      positive cell lines, but not if recombinant virus was used to infect EBV-negative
      B-cell lines or to immortalize peripheral blood B cells. EBV mutants lacking
      almost all of internal repeat 3, which encode a repetitive glycine and alanine
      domain of EBNA-1, were generated in the same way and found to immortalize B cells
      normally. An EBNA-1-deficient mutant of EBV was isolated and found to be
      incapable of establishing a latent infection of the cell line BL30 at a
      detectable frequency, indicating that the mutant was less than 1% as efficient as
      an isogenic, EBNA-1-positive strain in this assay. The data indicate that EBNA-1
      is required for efficient and stable latent infection by EBV under the conditions
      tested. Evidence from other studies now indicates that autonomous maintenance of
      the EBV chromosome during latent infection does not depend on the replication
      initiation function of oriP. It is therefore likely that the viral chromosome
      maintenance (segregation) function of oriP and EBNA-1 is what is required.

PMID- 10074148
TI  - Silencing of the Epstein-Barr virus latent membrane protein 1 gene by the Max
      Mad1-mSin3A modulator of chromatin structure.
AB  - The tumor-associated latent membrane protein 1 (LMP1) gene in the Epstein-Barr
      virus (EBV) genome is activated by EBV-encoded proteins and cellular factors that
      are part of general signal transduction pathways. As previously demonstrated, the
      proximal region of the LMP1 promoter regulatory sequence (LRS) contains a
      negative cis element with a major role in EBNA2-mediated regulation of LMP1 gene
      expression in B cells. Here, we show that this silencing activity overlaps with a
      transcriptional enhancer in an LRS sequence that contains an E-box-homologous
      motif. Mutation of the putative repressor binding site relieved the repression
      both in a promoter-proximal context and in a complete LRS context, indicating a
      functional role of the repressor. Gel retardation assays showed that members of
      the basic helix-loop-helix transcription factor family, including Max, Mad1, USF,
      E12, and E47, and the corepressor mSin3A bound to the E-box-containing sequence.
      The enhancer activity correlated with the binding of USF. Moreover, the activity
      of the LMP1 promoter in reporter constructs was upregulated by overexpression of
      USF1 and USF2a, and the transactivation was inhibited by the concurrent
      expression of Max and Mad1. This suggests that Max-Mad1-mediated anchorage of a
      multiprotein complex including mSin3A and histone deacetylases to the E-box site
      constitutes the basis for the repression. Removal of acetyl moieties from
      histones H3 and H4 should result in a chromatin structure that is inaccessible to
      transcription factors. Accordingly, inhibition of deacetylase activity with
      trichostatin A induced expression of the endogenous LMP1 gene in EBV-transformed
      cells.

PMID- 10074149
TI  - HMG protein family members stimulate human immunodeficiency virus type 1 and
      avian sarcoma virus concerted DNA integration in vitro.
AB  - We have reconstituted concerted human immunodeficiency virus type 1 (HIV-1)
      integration in vitro with specially designed mini-donor HIV-1 DNA, a supercoiled
      plasmid acceptor, purified bacterium-derived HIV-1 integrase (IN), and host HMG
      protein family members. This system is comparable to one previously described for
      avian sarcoma virus (ASV) (A. Aiyar et al., J. Virol. 70:3571-3580, 1996) that
      was stimulated by the presence of HMG-1. Sequence analyses of individual HIV-1
      integrants showed loss of 2 bp from the ends of the donor DNA and almost
      exclusive 5-bp duplications of the acceptor DNA at the site of integration. All
      of the integrants sequenced were inserted into different sites in the acceptor.
      These are the features associated with integration of viral DNA in vivo. We have
      used the ASV and HIV-1 reconstituted systems to compare the mechanism of
      concerted DNA integration and examine the role of different HMG proteins in the
      reaction. Of the three HMG proteins examined, HMG-1, HMG-2, and HMG-I(Y), the
      products formed in the presence of HMG-I(Y) for both systems most closely match
      those observed in vivo. Further analysis of HMG-I(Y) mutants demonstrates that
      the stimulation of integration requires an HMG-I(Y) domain involved in DNA
      binding. While complexes containing HMG-I(Y), ASV IN, and donor DNA can be
      detected in gel shift experiments, coprecipitation experiments failed to
      demonstrate stable interactions between HMG-I(Y) and ASV IN or between HMG-I(Y)
      and HIV-1 IN.

PMID- 10074150
TI  - The retinoblastoma protein alters the phosphorylation state of polyomavirus large
      T antigen in murine cell extracts and inhibits polyomavirus origin DNA
      replication.
AB  - The retinoblastoma tumor suppressor protein (pRb) can associate with the
      transforming proteins of several DNA tumor viruses, including the large T antigen
      encoded by polyomavirus (Py T Ag). Although pRb function is critical for
      regulating progression from G1 to S phase, a role for pRb in S phase has not been
      demonstrated or excluded. To identify a potential effect of pRb on DNA
      replication, pRb protein was added to reaction mixtures containing Py T Ag, Py
      origin-containing DNA (Py ori-DNA), and murine FM3A cell extracts. We found that
      pRb strongly represses Py ori-DNA replication in vitro. Unexpectedly, however,
      this inhibition only partially depends on the interaction of pRb with Py T Ag,
      since a mutant Py T Ag (dl141) lacking the pRb interaction region was also
      significantly inhibited by pRb. This result suggests that pRb interferes with or
      alters one or more components of the murine cell replication extract.
      Furthermore, the ability of Py T Ag to be phosphorylated in such extracts is
      markedly reduced in the presence of pRb. Since cyclin-dependent kinase (CDK)
      phosphorylation of Py T Ag is required for its replication function, we
      hypothesize that pRb interferes with this phosphorylation event. Indeed, the S
      phase CDK complex (cyclin A-CDK2), which phosphorylates both pRb and Py T Ag,
      alleviates inhibition caused by pRb. Moreover, hyperphosphorylated pRb is
      incapable of inhibiting replication of Py ori-DNA in vitro. We propose a new
      requirement for maintaining pRb phosphorylation in S phase, namely, to prevent
      deleterious effects on the cellular replication machinery.

PMID- 10074151
TI  - Glycoprotein gL-independent infectivity of pseudorabies virus is mediated by a gD
      gH fusion protein.
AB  - Envelope glycoproteins gH and gL, which form a complex, are conserved throughout
      the family Herpesviridae. The gH-gL complex is essential for the fusion between
      the virion envelope and the cellular cytoplasmic membrane during penetration and
      is also required for direct viral cell-to-cell spread from infected to adjacent
      noninfected cells. It has been proposed for several herpesviruses that gL is
      required for proper folding, intracellular transport, and virion localization of
      gH. In pseudorabies virus (PrV), glycoprotein gL is necessary for infectivity but
      is dispensable for virion localization of gH. A virus mutant lacking gL, PrV
      DeltagLbeta, is defective in entry into target cells, and direct cell-to-cell
      spread is drastically reduced, resulting in only single or small foci of infected
      cells (B. G. Klupp, W. Fuchs, E. Weiland, and T. C. Mettenleiter, J. Virol.
      71:7687-7695, 1997). We used this limited cell-to-cell spreading ability of PrV
      DeltagLbeta for serial passaging of cells infected with transcomplemented virus
      by coseeding with noninfected cells. After repeated passaging, plaque formation
      was restored and infectivity in the supernatant was observed. One single-plaque
      isolate, designated PrV-DeltagLPass, was further characterized. To identify the
      mutation leading to this gL-independent infectious phenotype, Southern and
      Western blot analyses, radioimmunoprecipitations, and DNA sequencing were
      performed. The results showed that rearrangement of a genomic region comprising
      part of the gH gene into a duplicated copy of part of the unique short region
      resulted in a fusion fragment predicted to encode a protein consisting of the N
      terminal 271 amino acids of gD fused to the C-terminal 590 residues of gH.
      Western blotting and radioimmunoprecipitation with gD- and gH-specific antibodies
      verified the presence of a gDH fusion protein. To prove that this fusion protein
      mediates infectivity of PrV-DeltagLPass, cotransfection of PrV-DeltagLbeta DNA
      with the cloned fusion fragment was performed, and a cell line, Nde-67, carrying
      the fusion gene was established. After cotransfection, infectious gL-negative PrV
      was recovered, and propagation of PrV-DeltagLbeta on Nde-67 cells produced
      infectious virions. Thus, a gDH fusion polypeptide can compensate for function of
      the essential gL in entry and cell-to-cell spread of PrV.

PMID- 10074152
TI  - Human immunodeficiency virus types 1 and 2 differ in the predominant mechanism
      used for selection of genomic RNA for encapsidation.
AB  - Retroviral RNA encapsidation is a highly selective process mediated through
      recognition by the viral Gag proteins of cis-acting RNA packaging signals in
      genomic RNA. This RNA species is also translated, producing the viral gag gene
      products. The relationship between these processes is poorly understood. Unlike
      that of human immunodeficiency virus type 1 (HIV-1), the dominant packaging
      signal of HIV-2 is upstream of the major splice donor and present in both
      unspliced and spliced viral RNAs, necessitating additional mechanisms for
      preferential packaging of unspliced genomic RNA. Encapsidation studies of a
      series of HIV-2-based vectors showed efficient packaging of viral genomes only if
      the unspliced, encapsidated RNA expressed full-length Gag protein, including
      functional nucleocapsid. We propose a novel encapsidation initiation mechanism,
      providing selectivity, in which unspliced HIV-2 RNA is captured in cis by the Gag
      protein. This has implications for the use of HIV-2 and other lentiviruses as
      vectors.

PMID- 10074153
TI  - Bamboo mosaic potexvirus satellite RNA (satBaMV RNA)-encoded P20 protein
      preferentially binds to satBaMV RNA.
AB  - A satellite RNA of 836 nucleotides [excluding the poly(A) tail] depends on the
      bamboo mosaic potexvirus (BaMV) for its replication and encapsidation. The BaMV
      satellite RNA (satBaMV) contains a single open reading frame encoding a 20-kDa
      nonstructural protein (P20). The P20 protein with eight histidine residues at the
      C terminus was overexpressed in Escherichia coli. Experiments of gel retardation,
      UV cross-linking, and Northwestern hybridization demonstrated that purified P20
      was a nucleic-acid-binding protein. The binding of P20 to nucleic acids was
      strong and highly cooperative. P20 preferred binding to satBaMV- or BaMV-related
      sequences rather than to nonrelated sequences. By deletion analysis, the P20
      binding sites were mainly located at the 5' and 3' untranslated regions of
      satBaMV RNA, and the RNA-protein interactions could compete with the poly(G) and,
      less efficiently, with the poly(U) homopolymers. The N-terminal arginine-rich
      motif of P20 was the RNA binding domain, as shown by in-frame deletion analysis.
      This is the first report that a plant virus satellite RNA-encoded nonstructural
      protein preferentially binds with nucleic acids.

PMID- 10074154
TI  - Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to
      Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.
AB  - We have sequenced the long unique region (LUR) and characterized the terminal
      repeats of the genome of a rhesus rhadinovirus (RRV), strain 17577. The LUR as
      sequenced is 131,364 bp in length, with a G+C content of 52.2% and a CpG ratio of
      1.11. The genome codes for 79 open reading frames (ORFs), with 67 of these ORFs
      similar to genes found in both Kaposi's sarcoma-associated herpesvirus (KSHV)
      (formal name, human herpesvirus 8) and herpesvirus saimiri. Eight of the 12
      unique genes show similarity to genes found in KSHV, including genes for viral
      interleukin-6, viral macrophage inflammatory protein, and a family of viral
      interferon regulatory factors (vIRFs). Genomic organization is essentially
      colinear with KSHV, the primary differences being the number of cytokine and IRF
      genes and the location of the gene for dihydrofolate reductase. Highly repetitive
      sequences are located in positions corresponding to repetitive sequences found in
      KSHV. Phylogenetic analysis of several ORFs supports the similarity between RRV
      and KSHV. Overall, the sequence, structural, and phylogenetic data combine to
      provide strong evidence that RRV 17577 is the rhesus macaque homolog of KSHV.

PMID- 10074155
TI  - Production and characterization of a soluble, active form of Tva, the subgroup A
      avian sarcoma and leukosis virus receptor.
AB  - The receptor for the subgroup A avian sarcoma and leukosis viruses [ASLV(A)] is
      the cellular glycoprotein Tva. A soluble form of Tva, sTva, was produced and
      purified with a baculovirus expression system. Using this system, 7 to 10 mg of
      purified sTva per liter of cultured Sf9 cells was obtained. Characterization of
      the carbohydrate modification of sTva revealed that the three N glycosylation
      sites in sTva were differentially utilized; however, the O glycosylation common
      to Tva produced in mammalian and avian cells was not observed. Purified sTva
      demonstrates significant biological activity, specifically blocking infection of
      avian cells by ASLV(A) with a 90% inhibitory concentration of approximately 25
      pM. A quantitative enzyme-linked immunosorbent assay, developed to assess the
      binding of sTva to ASLV envelope glycoprotein, demonstrates that sTva has a high
      affinity for EnvA, with an apparent dissociation constant of approximately 0.3
      nM. Once they are bound, a very stable complex is formed between EnvA and sTva,
      with an estimated complex half-life of 6 h. The soluble receptor protein
      described here represents a valuable tool for analysis of the receptor-envelope
      glycoprotein interaction and for structural analysis of Tva.

PMID- 10074156
TI  - Human papillomavirus type 18 E1 protein is translated from polycistronic mRNA by
      a discontinuous scanning mechanism.
AB  - Papillomaviruses are small double-stranded DNA viruses that replicate episomally
      in the nuclei of infected cells. The full-length E1 protein of papillomaviruses
      is required for the replication of viral DNA. The viral mRNA from which the human
      papillomavirus type 18 E1 protein is expressed is not known. We demonstrate that
      in eukaryotic cells, the E1 protein is expressed from polycistronic mRNA
      containing E6, E7, and E1 open reading frames (ORFs). The translation of adjacent
      E7 and E1 ORFs is not associated; it is performed by separate populations of
      ribosomes. The translation of the downstream E1 gene is preceded by ribosome
      scanning. Scanning happens at least at the 5' end of the polycistronic mRNA and
      also approximately 100 bp in front of the E1 gene. Long areas in middle of the
      mRNA are bypassed by ribosomes, possibly by ribosomal "shunting." Inactivation of
      short minicistrons in the upstream area of the E1 gene did not change the
      expression level of the E1 gene.

PMID- 10074157
TI  - Early region 1 transforming functions are dispensable for mammary tumorigenesis
      by human adenovirus type 9.
AB  - Some human adenoviruses are tumorigenic in rodents. Subgroup A and B human
      adenoviruses generally induce sarcomas in both male and female animals, and the
      gene products encoded within viral early region 1 (E1 region) are both necessary
      and sufficient for this tumorigenicity. In contrast, subgroup D human adenovirus
      type 9 (Ad9) induces estrogen-dependent mammary tumors in female rats and
      requires the E4 region-encoded ORF1 oncoprotein for its tumorigenicity.
      Considering the established importance of the viral E1 region for tumorigenesis
      by adenoviruses, we investigated whether this viral transcription unit is also
      necessary for Ad9 to generate mammary tumors. The nucleotide sequence of the Ad9
      E1 region indicated that the gene organization and predicted E1A and E1B
      polypeptides of Ad9 are closely related to those of other human adenovirus E1
      regions. In addition, an Ad9 E1 region plasmid demonstrated focus-forming
      activity in both low-passage-number and established rat embryo fibroblasts,
      whereas a large deletion within either the E1A or E1B gene of this plasmid
      diminished transforming activity. Surprisingly, we found that introducing the
      same transformation-inactivating E1A and E1B deletions into Ad9 results in mutant
      viruses that retain the ability to elicit mammary tumors in rats. These results
      are novel in showing that Ad9 represents a unique oncogenic adenovirus in which
      the E4 region, rather than the E1 region, encodes the major oncogenic determinant
      in the rat.

PMID- 10074158
TI  - T cells contribute to disease severity during coxsackievirus B4 infection.
AB  - By using a model of coxsackievirus B4-induced disease, the question of whether
      tissue damage is due to the virus or to immune-mediated mechanisms was addressed.
      Both viral replication and T-cell function were implicated in contributing to the
      severity of disease. Three stages (I to III) of disease, which correspond to
      periods of high viral titers, low viral titers, and no infectious virus, have
      been identified. Stage I disease is considered to be primarily the result of
      viral replication. Immunopathological mechanisms appear to contribute to the
      severity of stage II and III disease. To investigate the role of T cells in
      contributing to the severity of disease, viral infection in CD8 knockout (ko)
      mice and CD4 ko mice was analyzed. CD8 T-cell responses appear to be beneficial
      during early, viral disease but detrimental in later disease when viral titers
      are diminishing. CD4 ko mice, unlike the parental strain, survived infection.
      Viral replication was lower in the CD4 ko mice. Was survival due to decreased
      viral replication or to the lack of T-helper-cell function? To investigate
      further the role of T helper cells in contributing to tissue damage, viral
      infection in two additional ko strains (interleukin-4 [IL-4] ko and gamma
      interferon ko strains) was examined. A clear correlation between viral
      replication and the outcome of infection was not observed. The absence of IL-4,
      which may influence T-helper-cell subset development, was advantageous during
      early viral disease but deleterious in later disease. The results suggest that T
      cell-mediated immunity is both beneficial and detrimental during coxsackievirus
      B4 infection.

PMID- 10074159
TI  - Substitutions in the receptor-binding domain of the avian sarcoma and leukosis
      virus envelope uncouple receptor-triggered structural rearrangements in the
      surface and transmembrane subunits.
AB  - The retrovirus avian sarcoma and leukosis virus (ASLV) enters cells via pH
      independent membrane fusion. This reaction is catalyzed by the viral glycoprotein
      Env, composed of a membrane-distal subunit, SU, and a membrane-anchored subunit,
      TM. Previous mutational analysis of a variable region, central within the SU
      subunit, indicates that this region constitutes part of the receptor-binding
      domain for subgroup A envelope (EnvA) and furthermore that basic residues (R210,
      R213, R223, R224, and K227) within this region are critical determinants of
      efficient ASLV infection. Substitutions of these basic residues exert effects on
      both receptor binding and postbinding events in EnvA-mediated entry. In this
      study, we performed biochemical analysis of the EnvA protein from three of the
      receptor-binding domain mutants (R213A/K227A, R213A/R223A/R224A, and R213S) to
      define the role of this domain in early molecular events in the entry pathway.
      Protease sensitivity assays demonstrated that receptor binding was sufficient to
      trigger conformational changes in the SU subunit of mutants R213A/K227A and R213S
      similar to those in the wild-type EnvA, while R213A/R223A/R224A was
      constitutively sensitive to protease. In contrast, all three receptor-binding
      domain mutants disrupted receptor-triggered conversion of EnvA to an active,
      membrane-binding conformation as assessed by liposome flotation assays. Our
      results demonstrate that mutations in the receptor-binding site can dissociate
      receptor-triggered conformational changes in the SU subunit from membrane
      binding. Furthermore, they suggest that communication between the receptor
      binding subunit, SU, and the fusogenic subunit, TM, is crucial for efficient
      activation of the fusogenic state of EnvA. Analysis of these mutants continues
      earlier observations that binding to the cellular receptor provides the trigger
      for efficient activation of this pH-independent viral envelope protein.

PMID- 10074160
TI  - Yellow fever/Japanese encephalitis chimeric viruses: construction and biological
      properties.
AB  - A system has been developed for generating chimeric yellow fever/Japanese
      encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins
      prM and E of JE virus within the backbone of a molecular clone of the YF17D
      strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2
      (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged
      strain]), were studied in cell culture and laboratory mice. The JE envelope
      protein (E) retained antigenic and biological properties when expressed with its
      prM protein together with the YF capsid; however, viable chimeric viruses
      incorporating the entire JE structural region (C-prM-E) could not be obtained.
      YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito
      origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to
      kill young adult mice by intracerebral challenge, even at doses of 10(6) PFU. In
      contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled
      parental YF virus rather than JE-N. Ten predicted amino acid differences
      distinguish the JE E proteins of the two chimeric viruses, therefore implicating
      one or more residues as virus-specific determinants of mouse neurovirulence in
      this chimeric system. This study indicates the feasibility of expressing
      protective antigens of JE virus in the context of a live, attenuated flavivirus
      vaccine strain (YF17D) and also establishes a genetic system for investigating
      the molecular basis for neurovirulence determinants encoded within the JE E
      protein.

PMID- 10074161
TI  - The simian virus 40 small-t and large-T antigens jointly regulate cell cycle
      reentry in human fibroblasts.
AB  - Focus formation in human diploid fibroblasts (HDF cells) is known to require both
      the simian virus 40 (SV40) large-T and small-t antigens. Similarly, both SV40
      proteins were required to stimulate confluent, density-arrested HDF cells to
      reenter the cell cycle. This study used defective recombinant adenoviruses to
      examine the roles of the individual SV40 proteins in altering specific steps in
      the cell cycle. Small-t antigen and, to a lesser extent, large-T antigen
      increased the level of the S phase cyclin cyclin A but without increasing the
      activity of associated cyclin kinases unless the two SV40 proteins were
      coexpressed. The absence of kinase activity reflected the presence in density
      arrested cells of high levels of the cyclin-dependent kinase inhibitors p21(WAF1)
      and p27(KIP1). We report here that expression of SV40 large-T antigen reduced
      levels of p21(WAF1), while expression of small-t antigen was required to decrease
      p27(KIP1). The separate effects of large-T and small-t antigens on these two
      inhibitors may explain the joint requirement for the two proteins to drive cell
      cycle reentry of HDF cells and ultimately transform these cells.

PMID- 10074162
TI  - The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase
      functional domains of dengue virus type 2 NS3 converge within a region of 20
      amino acids.
AB  - NS3 protein of dengue virus type 2 has a serine protease domain within the N
      terminal 180 residues. NS2B is required for NS3 to form an active protease
      involved in processing of the viral polyprotein precursor. The region carboxy
      terminal to the protease domain has conserved motifs present in several viral RNA
      stimulated nucleoside triphosphatase (NTPase)/RNA helicases. To define the
      functional domains of protease and NTPase/RNA helicase activities of NS3, full
      length and amino-terminal deletion mutants of NS3 were expressed in Escherichia
      coli and purified. Deletion of 160 N-terminal residues of NS3 (as in NS3del.2)
      had no detrimental effect on the basal and RNA-stimulated NTPase as well as RNA
      helicase activities. However, mutagenesis of the conserved P-loop motif of the
      RNA helicase domain (K199E) resulted in loss of ATPase activity. The RNA
      stimulated NTPase activity was significantly affected by deletion of 20 amino
      acid residues from the N terminus or by substitutions of the cluster of basic
      residues, 184RKRK-->QNGN, of NS3del.2, although both mutant proteins retained the
      conserved RNA helicase motifs. Furthermore, the minimal NS3 protease domain,
      required for cleavage of the 2B-3 site, was precisely defined to be 167 residues,
      using the in vitro processing of NS2B-NS3 precursors. Our results reveal that the
      functional domains required for serine protease and RNA-stimulated NTPase
      activities map within the region between amino acid residues 160 and 180 of NS3
      protein and that a novel motif, the cluster of basic residues 184RKRK, plays an
      important role for the RNA-stimulated NTPase activity.

PMID- 10074163
TI  - Requirements for measles virus induction of RANTES chemokine in human astrocytoma
      derived U373 cells.
AB  - Interferons and chemokines play a critical role in regulating the host response
      to viral infection. Measles virus, a member of the Paramyxoviridae family,
      induces RANTES expression by astrocytes. We have examined the mechanism of this
      induction in U373 cells derived from a human astrocytoma. RANTES was induced in a
      dose- and time-dependent manner by measles virus infection. Inhibition of
      receptor binding by the anti-CD46 antibody TRA-2.10 and of virus-membrane fusion
      by the tripeptide X-Phe-Phe-Gly reduced RANTES expression. Formalin-inactivated
      virus, which can bind but not fuse, and extensively UV-irradiated virus, which
      can bind and fuse, were both ineffective. Therefore, virus binding to the
      cellular receptor CD46 and subsequent membrane fusion were necessary, but not
      sufficient, to induce RANTES. UV irradiation of virus for less than 10 min
      proportionally inhibited viral transcription and RANTES expression. RANTES
      induction was decreased in infected cells treated with ribavirin, which inhibits
      measles virus transcription. However, RANTES mRNA was superinduced by measles
      virus in the presence of cycloheximide. These data suggest that partial
      transcription of the viral genome is sufficient and necessary for RANTES
      induction, whereas viral protein synthesis and replication are not required. This
      hypothesis was supported by the fact that RANTES was induced through transient
      expression of the measles virus nucleocapsid gene but not by measles genes
      encoding P or L proteins or by leader RNA in A549 cells. Thus, transcription of
      specific portions of measles virus RNA, such as the nucleocapsid gene, appears
      able to generate the specific signaling required to induce RANTES gene
      expression.

PMID- 10074164
TI  - Sendai virus and simian virus 5 block activation of interferon-responsive genes:
      importance for virus pathogenesis.
AB  - Sendai virus (SeV) is highly pathogenic for mice. In contrast, mice (including
      SCID mice) infected with simian virus 5 (SV5) showed no overt signs of disease.
      Evidence is presented that a major factor which prevented SV5 from productively
      infecting mice was its inability to circumvent the interferon (IFN) response in
      mice. Thus, in murine cells that produce and respond to IFN, SV5 protein
      synthesis was rapidly switched off. In marked contrast, once SeV protein
      synthesis began, it continued, even if the culture medium was supplemented with
      alpha/beta IFN (IFN-alpha/beta). However, in human cells, IFN-alpha/beta did not
      inhibit the replication of either SV5 or SeV once virus protein synthesis was
      established. To begin to address the molecular basis for these observations, the
      effects of SeV and SV5 infections on the activation of an IFN-alpha/beta
      responsive promoter and on that of the IFN-beta promoter were examined in
      transient transfection experiments. The results demonstrated that (i) SeV, but
      not SV5, inhibited an IFN-alpha/beta-responsive promoter in murine cells; (ii)
      both SV5 and SeV inhibited the activation of an IFN-alpha/beta-responsive
      promoter in human cells; and (iii) in both human and murine cells, SeV was a
      strong inducer of the IFN-beta promoter, whereas SV5 was a poor inducer. The
      ability of SeV and SV5 to inhibit the activation of IFN-responsive genes in human
      cells was confirmed by RNase protection experiments. The importance of these
      results in terms of paramyxovirus pathogenesis is discussed.

PMID- 10074165
TI  - Protection of macaques against intrarectal infection by a combination
      immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160
      vaccines.
AB  - We previously reported that immunization with recombinant simian immunodeficiency
      virus SIVmne envelope (gp160) vaccines protected macaques against intravenous
      challenge by the cloned homologous virus E11S but that this protection was only
      partially effective against the uncloned virus, SIVmne. In the present study, we
      examine the protective efficacy of this immunization regimen against infection by
      a mucosal route. We found that the same gp160-based vaccines were highly
      effective against intrarectal infection not only with the E11S clone but also
      with the uncloned SIVmne. Protection against mucosal infection is therefore
      achievable by parenteral immunization with recombinant envelope vaccines.
      Protection appears to correlate with high levels of SIV-specific antibodies and,
      in animals protected against the uncloned virus, the presence of serum
      neutralizing activities. To understand the basis for the differential efficacies
      against the uncloned virus by the intravenous versus the intrarectal routes, we
      examined viral sequences recovered from the peripheral blood mononuclear cells of
      animals early after infection by both routes. We previously showed that the
      majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences
      homologous to the molecular clone from which the vaccines were made (E11S type),
      with the remainder (15%) containing multiple conserved changes (the variant
      types). In contrast to intravenously infected animals, from which either E11S
      type or the variant type V1 sequences could be recovered in significant
      proportions, animals infected intrarectally had predominantly E11S-type
      sequences. Preferential transmission or amplification of the E11S-type viruses
      may therefore account in part for the enhanced efficacy of the recombinant gp160
      vaccines against the uncloned virus challenge by the intrarectal route compared
      with the intravenous route.

PMID- 10074166
TI  - Rotavirus capsid protein VP5* permeabilizes membranes.
AB  - Proteolytic cleavage of the VP4 outer capsid spike protein into VP8* and VP5*
      proteins is required for rotavirus infectivity and for rotavirus-induced membrane
      permeability. In this study we addressed the function of the VP5* cleavage
      fragment in permeabilizing membranes. Expressed VP5* and truncated VP5* proteins
      were purified by nickel affinity chromatography and assayed for their ability to
      permeabilize large unilamellar vesicles (LUVs) preloaded with carboxyfluorescein
      (CF). VP5* and VP5* truncations, but not VP4 or VP8*, permeabilized LUVs as
      measured by fluorescence dequenching of released CF. Similar to virus-induced CF
      release, VP5*-induced CF release was concentration and temperature dependent,
      with a pH optimum of 7.35 at 37 degrees C, but independent of the presence of
      divalent cations or cholesterol. VP5*-induced permeability was completely
      inhibited by VP5*-specific neutralizing monoclonal antibodies (2G4, M2, or M7)
      which recognize conformational epitopes on VP5* but was not inhibited by VP8*
      specific neutralizing antibodies. In addition, N-terminal and C-terminal VP5*
      truncations including residues 265 to 474 are capable of permeabilizing LUVs.
      These findings demonstrate that VP5* permeabilizes membranes in the absence of
      other rotavirus proteins and that membrane-permeabilizing VP5* truncations
      contain the putative fusion region within predicted virion surface domains. The
      ability of recombinant expressed VP5* to permeabilize membranes should permit us
      to functionally define requirements for VP5*-membrane interactions. These
      findings indicate that VP5* is a specific membrane-permeabilizing capsid protein
      which is likely to play a role in the cellular entry of rotaviruses.

PMID- 10074167
TI  - Expression of EBNA-1 mRNA is regulated by cell cycle during Epstein-Barr virus
      type I latency.
AB  - Expression of EBNA-1 protein is required for the establishment and maintenance of
      the Epstein-Barr virus (EBV) genome during latent infection. During type I
      latency, the BamHI Q promoter (Qp) gives rise to EBNA-1 expression. The dominant
      regulatory mechanism for Qp appears to be mediated through the Q locus, located
      immediately downstream of the transcription start site. Binding of EBNA-1 to the
      Q locus represses Qp constitutive activity, and repression has been reported to
      be overcome by an E2F family member that binds to the Q locus and displaces EBNA
      1 (N. S. Sung, J. Wilson, M. Davenport, N. D. Sista, and J. S. Pagano, Mol. Cell.
      Biol. 14:7144-7152, 1994). These data suggest that the final outcome of Qp
      activity is reciprocally controlled by EBNA-1 and E2F. Since E2F activity is cell
      cycle regulated, Qp activity and EBNA-1 expression are predicted to be regulated
      in a cell cycle-dependent manner. Proliferation of the type I latently infected
      cell line, Akata, was synchronized with the use of the G2/M blocking agent
      nocodazole. From 65 to 75% of cells could be made to peak in S phase without
      evidence of viral reactivation. Following release from G2/M block, EBNA-1 mRNA
      levels declined as the synchronized cells entered the G1 phase of the cell cycle.
      As cells proceeded into S phase, EBNA-1 mRNA levels increased parallel to the
      peak in cell numbers in S phase. However, EBNA-1 protein levels showed no
      detectable change during the cell cycle, most likely due to the protein's long
      half-life as estimated by inhibition of protein synthesis by cycloheximide.
      Finally, in Qp luciferase reporter assays, the activity of Qp was shown to be
      regulated by cell cycle and to be dependent on the E2F sites within the Q locus.
      These findings demonstrate that transcriptional activity of Qp is cell cycle
      regulated and indicated that E2F serves as the stimulus for this regulation.

PMID- 10074168
TI  - Recombinant duck interferon gamma inhibits duck hepatitis B virus replication in
      primary hepatocytes.
AB  - Interferon gamma (IFN-gamma), which has been cloned in several mammalian species
      and recently in birds, plays a critical role in modulating immune system
      function. IFN-gamma and tumor necrosis factor alpha (TNF-alpha) have been shown
      to be crucial in the pathogenesis of viral hepatitis and in the transient
      disappearance of hepatitis B virus (HBV) from the liver after adoptive transfer
      of HBV-specific cytotoxic T lymphocytes into HBV-transgenic mice. Similar studies
      in the natural animal hosts of related hepadnaviruses have been limited because
      the corresponding probes and recombinant cytokines were not available. For this
      reason, we initiated studies to clone and characterize cytokines from the duck,
      the natural host of the duck hepatitis B virus (DHBV). We describe here the cDNA
      cloning and initial characterization of the IFN-gamma homologue of ducks (DuIFN
      gamma). The DuIFN-gamma cDNA codes for a predicted mature protein of 145 amino
      acids with a molecular mass of 16.6 kDa. The precursor protein has 67% identity
      with the previously cloned chicken IFN-gamma and 21 to 34% identity with
      mammalian IFN-gamma. Recombinant DuIFN-gamma induces the transcription of several
      IFN-inducible genes including IFN regulatory factor 1 and guanylate-binding
      protein, and it exhibits antiviral activity that protects duck cells from
      vesicular stomatitis virus-mediated lysis. Importantly, treatment of primary duck
      hepatocytes with recombinant DuIFN-gamma inhibits DHBV replication in a dose
      dependent fashion. Time course analysis revealed that IFN-gamma treatment does
      not affect initial covalently closed circular DNA (cccDNA) conversion but
      inhibits the synthesis of progeny cccDNA by amplification.

PMID- 10074169
TI  - Amphotropic murine leukemia virus entry is determined by specific combinations of
      residues from receptor loops 2 and 4.
AB  - Pit2 is the human receptor for amphotropic murine leukemia virus (A-MuLV); the
      related human protein Pit1 does not support A-MuLV entry. Interestingly, chimeric
      proteins in which either the N-terminal or the C-terminal part of Pit2 was
      replaced by the Pit1 sequence all retained A-MuLV receptor function. A possible
      interpretation of these observations is that Pit1 harbors sequences which can
      specify A-MuLV receptor function when presented in a protein context other than
      Pit1, e.g., in Pit1-Pit2 hybrids. We reasoned that such Pit1 sequences might be
      identified if presented in the Neurospora crassa protein Pho-4. This protein is
      distantly related to Pit1 and Pit2, predicted to have a similar membrane topology
      with five extracellular loops, and does not support A-MuLV entry. We show here
      that introduction of the Pit1-specific loop 2 sequence conferred A-MuLV receptor
      function upon Pho-4. Therefore, we conclude that (i) a functional A-MuLV receptor
      can be constructed by combining sequences from two proteins each lacking A-MuLV
      receptor function and that (ii) a Pit1 sequence can specify A-MuLV receptor
      function when presented in another protein context than that provided by Pit1
      itself. Previous results indicated a role of loop 4 residues in A-MuLV entry, and
      the presence of a Pit2-specific loop 4 sequence was found here to confer A-MuLV
      receptor function upon Pho-4. Moreover, the introduction of a Pit1-specific loop
      4 sequence, but not of a Pit2-specific loop 4 sequence, abolished the A-MuLV
      receptor function of a Pho-4 chimera harboring the Pit1-specific loop 2 sequence.
      Together, these data suggest that residues in both loop 2 and loop 4 play a role
      in A-MuLV receptor function. A-MuLV is, however, not dependent on the specific
      Pit2 loop 2 and Pit2 loop 4 sequences for entry; rather, the role played by loops
      2 and 4 in A-MuLV entry can be fulfilled by several different combinations of
      loop 2 and loop 4 sequences. We predict that the residues in loops 2 and 4,
      identified in this study as specifying A-MuLV receptor function, are to be found
      among those not conserved among Pho-4, Pit1, and Pit2.

PMID- 10074170
TI  - Dissecting the role of the N-terminal domain of human immunodeficiency virus
      integrase by trans-complementation analysis.
AB  - The human immunodeficiency virus (HIV) integrase protein (IN) catalyzes two
      reactions required to integrate HIV DNA into the human genome: 3' processing of
      the viral DNA ends and integration. IN has three domains, the N-terminal zinc
      binding domain, the catalytic core, and the C-terminal SH3 domain. Previously, it
      was shown that IN proteins mutated in different domains could complement each
      other. We now report that this does not require any overlap between the two
      complementing proteins; an N-terminal domain, provided in trans, can restore IN
      activity of a mutant lacking this domain. Only the zinc-coordinating form of the
      N-terminal domain can efficiently restore IN activity of an N-terminal deletion
      mutant. This suggests that interaction between different domains of IN is needed
      for functional multimerization. We find that the N-terminal domain of feline
      immunodeficiency virus IN can support IN activity of an N-terminal deletion
      mutant of HIV type 2 IN. These cross-complementation experiments indicate that
      the N-terminal domain contributes to the recognition of specific viral DNA ends.

PMID- 10074171
TI  - Biological heterogeneity, including systemic replication in mice, of H5N1
      influenza A virus isolates from humans in Hong Kong.
AB  - An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997.
      Although the virus causes systemic infection and is highly lethal in chickens
      because of the susceptibility of the hemagglutinin to furin and PC6 proteases, it
      is not known whether it also causes systemic infection in humans. The clinical
      outcomes of infection in Hong Kong residents ranged widely, from mild respiratory
      disease to multiple organ failure leading to death. Therefore, to understand the
      pathogenesis of influenza due to these H5N1 isolates, we investigated their
      virulence in mice. The results identified two distinct groups of viruses: group
      1, for which the dose lethal for 50% of mice (MLD50) was between 0.3 and 11 PFU,
      and group 2, for which the MLD50 was more than 10(3) PFU. One day after
      intranasal inoculation of mice with 100 PFU of group 1 viruses, the virus titer
      in lungs was 10(7) PFU/g or 3 log units higher than that for group 2 viruses.
      Both types of viruses had replicated to high titers (>10(6) PFU/g) in the lungs
      by day 3 and maintained these titers through day 6. More importantly, only the
      group 1 viruses caused systemic infection, replicating in nonrespiratory organs,
      including the brain. Immunohistochemical analysis demonstrated the replication of
      a group 1 virus in brain neurons and glial cells and in cardiac myofibers.
      Phylogenetic analysis of all viral genes showed that both groups of Hong Kong
      H5N1 viruses had formed a lineage distinct from those of other viruses and that
      genetic reassortment between H5N1 and H1 or H3 human viruses had not occurred.
      Since mice and humans harbor both the furin and the PC6 proteases, we suggest
      that the virulence mechanism responsible for the lethality of influenza viruses
      in birds also operates in mammalian hosts. The failure of some H5N1 viruses to
      produce systemic infection in our model indicates that multiple, still-to-be
      identified, factors contribute to the severity of H5N1 infection in mammals. In
      addition, the ability of these viruses to produce systemic infection in mice and
      the clear differences in pathogenicity among the isolates studied here indicate
      that this system provides a useful model for studying the pathogenesis of avian
      influenza virus infection in mammals.

PMID- 10074172
TI  - Distinct attenuation phenotypes caused by mutations in the translational starting
      window of Theiler's murine encephalomyelitis virus.
AB  - Upon initiation of translation of picornavirus RNA, the ribosome is believed to
      bind the internal ribosome entry site of the template and then to form a
      productive complex with a downstream RNA segment, the starting window. The
      presence or absence of an AUG triplet within the starting window of the RNA of
      Theiler's murine encephalomyelitis virus (a picornavirus) is known to modulate
      its neurovirulence. In this study, mutants of this virus in which the starting
      windows, lying upstream of the viral polyprotein reading frame, had AUGs with
      different nonoptimal contexts were engineered. Upon intracerebral inoculation of
      mice, the mutants proved to be partially attenuated, as judged by a significant
      increase in the dose causing paralysis in 50% of the animals (PD50). Mutants with
      similar PD50s might differ from one another by eliciting either a severe, fatal
      tetraplegy or only mild, recoverable neurologic lesions. Some of the mutants
      triggered a chronic inflammatory reaction in the white matter of the spinal cord
      in the absence of detectable viral RNA or antigen. Thus, point mutations changing
      the context of an AUG within the starting window outside the polyprotein reading
      frame may differently affect the morbidity and mortality caused by a viral
      infection and may result in distinct attenuation phenotypes.

PMID- 10074173
TI  - Transcriptional repression of human hepatitis B virus genes by a bZIP family
      member, E4BP4.
AB  - Box alpha is an essential element of both the upstream regulatory sequence of the
      core promoter and the second enhancer, which positively regulate the
      transcription of human hepatitis B virus (HBV) genes. In this paper, we describe
      the cloning and characterization of a box alpha binding protein, E4BP4. E4BP4 is
      a bZIP type of transcription factor. Overexpression of E4BP4 represses the
      stimulating activity of box alpha in the upstream regulatory sequence of the core
      promoter and the second enhancer in differentiated human hepatoma cell lines.
      E4BP4 can also suppress the transcription of HBV genes and the production of HBV
      virions in a transient-transfection system that mimics the viral infection in
      vivo. Expression of an E4BP4 antisense transcript can, instead, elevate the
      transcription of the core promoter. A low abundance of E4BP4 protein and mRNA in
      differentiated human hepatoma cell lines is detected, and E4BP4 is not a major
      component of box alpha binding proteins in untransfected differentiated human
      hepatoma cell lines. C/EBPalpha and C/EBPbeta, in contrast, are major components
      of the box alpha binding activity present in nuclear extracts. E4BP4 has a
      stronger binding affinity towards box alpha than the endogenous box alpha binding
      activity present in nuclear extracts. Structure and function analysis of E4BP4
      reveals that DNA binding activity is sufficient to confer the negative regulatory
      function of E4BP4. These results indicate that binding site occlusion is the
      mechanism whereby E4BP4 suppresses transcription in HBV.

PMID- 10074174
TI  - Visualization of tegument-capsid interactions and DNA in intact herpes simplex
      virus type 1 virions.
AB  - Herpes simplex virus type 1 virions were examined by electron cryomicroscopy,
      allowing the three-dimensional structure of the infectious particle to be
      visualized for the first time. The capsid shell is identical to that of B-capsids
      purified from the host cell nucleus, with the exception of the penton channel,
      which is closed. The double-stranded DNA genome is organized as regularly spaced
      ( approximately 26 A) concentric layers inside the capsid. This pattern suggests
      a spool model for DNA packaging, similar to that for some bacteriophages. The
      bulk of the tegument is not icosahedrally ordered. However, a small portion
      appears as filamentous structures around the pentons, interacting extensively
      with the capsid. Their locations and interactions suggest possible roles for the
      tegument proteins in regulating DNA transport through the penton channel and
      binding to cellular transport proteins during viral infection.

PMID- 10074175
TI  - Herpes simplex virus 1 blocks caspase-3-independent and caspase-dependent
      pathways to cell death.
AB  - Earlier reports have shown that herpes simplex virus 1 (HSV-1) mutants induce
      programmed cell death and that wild-type HSV blocks the execution of the cell
      death program triggered by viral gene products, by the effectors of the immune
      system such as the Fas and tumor necrosis factor pathways, or by nonspecific
      stress agents such as either osmotic shock induced by sorbitol or thermal shock.
      A report from this laboratory showed that caspase inhibitors do not block DNA
      fragmentation induced by infection with the HSV-1 d120 mutant. To identify the
      events in programmed cell death induced and blocked by HSV-1, we examined cells
      infected with wild-type virus or the d120 mutant or cells infected and exposed to
      sorbitol. We report that: (i) the HSV-1 d120 mutant induced apoptosis by a
      caspase-3-independent pathway inasmuch as caspase 3 was not activated and DNA
      fragmentation was not blocked by caspase inhibitors even though the virus caused
      cytochrome c release and depolarization of the inner mitochondrial membrane. (ii)
      Cells infected with wild-type HSV-1 exhibited none of the manifestations
      associated with programmed cell death assayed in these studies. (iii) Uninfected
      cells exposed to osmotic shock succumbed to caspase-dependent apoptosis inasmuch
      as cytochrome c was released, the inner mitochondrial potential was lost, caspase
      3 was activated, and chromosomal DNA was fragmented. (iv) Although caspase-3 was
      activated in cells infected with wild-type HSV-1 and exposed to sorbitol,
      cytochrome c outflow, depolarization of the inner mitochondrial membrane, and DNA
      fragmentation were blocked. We conclude that although d120 induces apoptosis by a
      caspase-3-independent pathway, the wild-type virus blocks apoptosis induced by
      this pathway and also blocks the caspase-dependent pathway induced by osmotic
      shock. The block in the caspase-dependent pathway may occur downstream of caspase
      3 activation.

PMID- 10074176
TI  - Differentiation of M1 myeloid precursor cells into macrophages results in binding
      and infection by Theiler's murine encephalomyelitis virus and apoptosis.
AB  - Infection of susceptible mouse strains with BeAn, a less virulent strain of
      Theiler's murine encephalomyelitis virus (TMEV), results in immune system
      mediated demyelinating lesions in the central nervous system (CNS) similar to
      those in multiple sclerosis. Since macrophages appear to carry the major
      detectable antigen burden in vivo, and purification of sufficient cell numbers
      from the CNS for detailed analysis is difficult, macrophage-like cell lines
      provide an accessible system with which to study virus-macrophage interactions.
      The myeloid precursor cell line M1 differentiates in response to cytokines and
      expresses many characteristics of tissue macrophages. Incubation of TMEV with
      undifferentiated M1 cells produced neither infection nor apoptosis, whereas
      differentiated M1 (M1-D) cells developed a restricted virus infection and changes
      indicative of apoptosis. Virus binding and RNA replication as well as cellular
      production of alpha/beta interferons increased with differentiation. Although the
      amount of infectious virus was highly restricted, BeAn-infected M1-D cells
      synthesized and appropriately processed virus capsid proteins at levels
      comparable to those for permissive BHK-21 cells. Analysis of Bcl-2 protein family
      expression in undifferentiated and differentiated cells suggests that
      susceptibility of M1-D cells to apoptosis may be controlled, in part, by
      expression of the proapoptotic alpha isoform of Bax and Bak. These data suggest
      that macrophage differentiation plays a role in susceptibility to TMEV infection
      and apoptosis.

PMID- 10074177
TI  - Mutational analysis of Vpr-induced G2 arrest, nuclear localization, and cell
      death in fission yeast.
AB  - Cell cycle G2 arrest, nuclear localization, and cell death induced by human
      immunodeficiency virus type 1 Vpr were examined in fission yeast by using a panel
      of Vpr mutations that have been studied previously in human cells. The effects of
      the mutations on Vpr functions were highly similar between fission yeast and
      human cells. Consistent with mammalian cell studies, induction of cell cycle G2
      arrest by Vpr was found to be independent of nuclear localization. In addition,
      G2 arrest was also shown to be independent of cell killing, which only occurred
      when the mutant Vpr localized to the nucleus. The C-terminal end of Vpr is
      crucial for G2 arrest, the N-terminal alpha-helix is important for nuclear
      localization, and a large part of the Vpr protein is responsible for cell
      killing. It is evident that the overall structure of Vpr is essential for these
      cellular effects, as N- and C-terminal deletions affected all three cellular
      functions. Furthermore, two single point mutations (H33R and H71R), both of which
      reside at the end of each alpha-helix, disrupted all three Vpr functions,
      indicating that these two mutations may have strong effects on the overall Vpr
      structure. The similarity of the mutant effects on Vpr function in fission yeast
      and human cells suggests that fission yeast can be used as a model system to
      evaluate these Vpr functions in naturally occurring viral isolates.

PMID- 10074178
TI  - Analysis of the phosphorylation sites of herpes simplex virus type 1 regulatory
      protein ICP27.
AB  - The herpes simplex virus type 1 (HSV-1) regulatory protein ICP27 is a 63-kDa
      phosphoprotein required for viral replication. ICP27 has been shown to contain
      both stable phosphate groups and phosphate groups that cycle on and off during
      infection (K. W. Wilcox, A. Kohn, E. Sklyanskaya, and B. Roizman, J. Virol.
      33:167-182, 1980). Despite extensive genetic analysis of the ICP27 gene, there is
      no information available about the sites of the ICP27 molecule that are
      phosphorylated during viral infection. In this study, we mapped several of the
      phosphorylation sites of ICP27 following in vivo radiolabeling. Phosphoamino acid
      analysis showed that serine is the only amino acid that is phosphorylated during
      infection. Two-dimensional phosphopeptide mapping showed a complex tryptic
      phosphopeptide pattern with at least four major peptides and several minor
      peptides. In addition, ICP27 purified from transfected cells yielded a similar
      phosphopeptide pattern, suggesting that cellular kinases phosphorylate ICP27
      during viral infection. In vitro labeling showed that protein kinase A (PKA),
      PKC, and casein kinase II (CKII) were able to differentially phosphorylate ICP27,
      resulting in distinct phosphopeptide patterns. The major phosphorylation sites of
      ICP27 appeared to cluster in the N-terminal portion of the protein, such that a
      frameshift mutant that encodes amino acids 1 to 163 yielded a phosphopeptide
      pattern very similar to that seen with the wild-type protein. Further, using
      small deletion and point mutations in kinase consensus sites, we have elucidated
      individual serine residues that are phosphorylated in vivo. Specifically, the
      serine at residue 114 was highly phosphorylated by PKA and the serine residues at
      positions 16 and 18 serve as targets for CKII phosphorylation in vivo. These
      kinase consensus site mutants were still capable of complementing the growth of
      an ICP27-null mutant virus. Interestingly, phosphorylation of the serine at
      residue 114, which lies within the major nuclear localization signal, appeared to
      modulate the efficiency of nuclear import of ICP27.

PMID- 10074179
TI  - Interaction of Gli2 with CREB protein on DNA elements in the long terminal repeat
      of human T-cell leukemia virus type 1 is responsible for transcriptional
      activation by tax protein.
AB  - The long terminal repeat (LTR) of human T-cell leukemia virus type 1 (HTLV-1) has
      two distinct DNA elements, one copy of TRE2S and three copies of a 21-bp sequence
      that respond to the viral trans-activator protein, Tax. Either multiple copies of
      the 21-bp sequence or a combination of one copy each of TRE2S and 21-bp sequence
      is required for efficient trans activation by Tax. In the trans activation of
      multiple copies of 21-bp sequence, CREB/ATF protein plays an essential role in
      forming a complex with Tax. To understand the role of TRE2S in trans activation
      of one copy of 21-bp sequence, we examined protein binding to the DNA elements by
      DNA affinity precipitation assay including Gli2 protein binding to TRE2S and CREB
      protein binding to 21-bp sequence. Binding of CREB to a DNA probe containing both
      elements, TRE2S-21bp probe, was dependent on Gli2 protein under restricted
      conditions and was enhanced in a dose-dependent fashion by the binding of Gli2
      protein to the same probe. Mutation in either element abolished the efficient
      binding of CREB. A glutathione S-transferase fusion protein of a fragment of Gli2
      was able to bind to CREB. Therefore, Gli2-CREB interaction on the DNA probe is
      proposed to stabilize CREB binding to DNA. Tax can bind to CREB protein on the
      DNA; therefore, stabilization of DNA binding of CREB results in more recruitment
      of Tax onto DNA. Conversely, Tax increased the DNA binding of CREB, although it
      had almost no effect on the binding of Gli2. These results suggest that Gli2
      binds to the DNA element and interacts with CREB, resulting in more recruitment
      of Tax, which in turn stabilizes DNA binding of CREB. Similar cooperation of the
      protein binding to TRE2S-21bp probe was also observed in nuclear extract of an
      HTLV-1-infected T-cell line. Consistent with the Gli2-CREB interaction on the DNA
      elements, Tax-mediated trans activation was dependent on the size of the spacer
      between TRE2S and 21-bp sequence. The effective sizes of the spacer suggest that
      TRE2S in the LTR would cooperate with the second and third copies of the 21-bp
      sequence and contribute to trans activation of the viral gene transcription.

PMID- 10074180
TI  - The bovine papillomavirus E5 protein requires a juxtamembrane negative charge for
      activation of the platelet-derived growth factor beta receptor and transformation
      of C127 cells.
AB  - The bovine papillomavirus E5 gene encodes a 44-amino-acid, homodimeric
      transmembrane protein that is the smallest known transforming protein. The E5
      protein transforms cultured fibroblasts by forming a stable complex with the
      endogenous platelet-derived growth factor (PDGF) beta receptor through
      transmembrane and juxtamembrane interactions, leading to sustained receptor
      activation. Aspartic acid 33 in the extracellular juxtamembrane region of the E5
      protein is important for cell transformation and interaction with the PDGF beta
      receptor. A. N. Meyer et al. (Proc. Natl. Acad. Sci USA 91:4634-4638, 1994)
      speculated that this residue interacted with lysine 499 on the receptor. We
      constructed E5 mutants containing all possible substitutions at position 33, as
      well as several double mutants containing substitutions at aspartic acid 33 and
      at glutamic acid 36, and we examined the ability of these mutants to transform
      C127 mouse fibroblasts and to bind to and induce activation of the PDGF beta
      receptor. There was an excellent correlation between the transformation
      activities of the various mutants and their ability to bind to and activate the
      PDGF beta receptor. Analysis of the mutants demonstrated that a juxtamembrane
      negative charge on the E5 protein was required for cell transformation and for
      productive interaction with the PDGF beta receptor and indicated that aspartic
      acid 33 was more important for these activities than was glutamic acid 36. These
      results are consistent with the existence of an essential juxtamembrane salt
      bridge between lysine 499 on the PDGF beta receptor and an acidic residue in the
      C terminus of the E5 protein and lend support to our proposed model for the
      complex between the E5 dimer and the PDGF beta receptor.

PMID- 10074181
TI  - Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in
      peritoneal cells.
AB  - B cells have previously been identified as the major hematopoietic cell type
      harboring latent gammaherpesvirus 68 (gammaHV68) (N. P. Sunil-Chandra, S.
      Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275-3279, 1992). However, we have
      shown that gammaHV68 efficiently establishes latency in B-cell-deficient mice (K.
      E. Weck, M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin, J. Virol.
      70:6775-6780, 1996), demonstrating that B cells are not required for gammaHV68
      latency. To understand this dichotomy, we determined whether hematopoietic cell
      types, in addition to B cells, carry latent gammaHV68. We observed a high
      frequency of cells that reactivate latent gammaHV68 in peritoneal exudate cells
      (PECs) derived from both B-cell-deficient and normal C57BL/6 mice. PECs were
      composed primarily of macrophages in B-cell-deficient mice and of macrophages
      plus B cells in normal C57BL/6 mice. To determine which cells in PECs from
      C57BL/6 mice carry latent gammaHV68, we developed a limiting-dilution PCR assay
      to quantitate the frequency of cells carrying the gammaHV68 genome in
      fluorescence-activated cell sorter-purified cell populations. We also quantitated
      the contribution of individual cell populations to the total frequency of cells
      carrying latent gammaHV68. At early times after infection, the frequency of PECs
      that reactivated gammaHV68 correlated very closely with the frequency of PECs
      carrying the gammaHV68 genome, validating measurement of the frequency of viral
      genome-positive cells as a measure of latency in this cell population. F4/80
      positive macrophage-enriched, lymphocyte-depleted PECs harbored most of the
      gammaHV68 genome and efficiently reactivated gammaHV68, while CD19-positive, B
      cell-enriched PECs harbored about a 10-fold lower frequency of gammaHV68 genome
      positive cells. CD4-positive, T-cell-enriched PECs contained only a very low
      frequency of gammaHV68 genome-positive cells, consistent with previous analyses
      indicating that T cells are not a reservoir for gammaHV68 latency (N. P. Sunil
      Chandra, S. Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275-3279, 1992). Since
      macrophages are bone marrow derived, we determined whether elicitation of a large
      inflammatory response in the peritoneum would recruit additional latent cells
      into the peritoneum. Thioglycolate inoculation increased the total number of PECs
      by about 20-fold but did not affect the frequency of cells that reactivate
      gammaHV68, consistent with a bone marrow reservoir for latent gammaHV68. These
      experiments demonstrate gammaHV68 latency in two different hematopoietic cell
      types, F4/80-positive macrophages and CD19-positive B cells, and argue for a bone
      marrow reservoir for latent gammaHV68.

PMID- 10074182
TI  - The U69 gene of human herpesvirus 6 encodes a protein kinase which can confer
      ganciclovir sensitivity to baculoviruses.
AB  - The protein encoded by the U69 open reading frame (ORF) of human herpesvirus 6
      (HHV-6) has been predicted to be a protein kinase. To investigate its functional
      properties, we have expressed the U69 ORFs from both HHV-6 variants, A and B, by
      using recombinant baculoviruses (BV6AU69 and BV6BU69). Nickel agarose and
      antibody affinity chromatography was used to purify the proteins to homogeneity
      and when incubated with [gamma-32P]ATP, both U69 proteins became phosphorylated
      on predominantly serine residues. These data strongly suggest that U69 is a
      protein kinase which autophosphorylates. The phosphorylation reaction was optimal
      at physiological pH and low NaCl concentrations. It required the presence of Mg2+
      or Mn2+, and Mg2+ was able to support phosphorylation over a wider range of
      concentrations than Mn2+. Both ATP and GTP could donate phosphate in the protein
      kinase assay and the former was more efficient. U69 was capable of
      phosphorylating histone and casein (serine/threonine kinase substrates) but not
      enolase (a tyrosine kinase substrate). For the autophosphorylation reaction, the
      Michaelis constants for ATP of baculovirus-expressed HHV-6A and HHV-6B U69 were
      calculated to be 44 and 11 microM, respectively. U69 is a homologue of the UL97
      gene encoded by human cytomegalovirus which has been shown to phosphorylate the
      antiviral drug ganciclovir (GCV). We analyzed whether the U69 ORF alone was
      capable of conferring GCV sensitivity on baculoviruses BV6AU69 and BV6BU69. In
      plaque reduction experiments, these baculoviruses displayed a GCV-sensitive
      phenotype compared to a control baculovirus (BVLacZ). The 50% inhibitory
      concentrations (IC50) of BV6AU69 and BV6BU69 were calculated to be 0.35 and 0.26
      mM, respectively, whereas the control baculovirus had an IC50 of >1.4 mM. This
      shows that the U69 gene product is the only one required to confer GCV
      sensitivity on baculovirus.

PMID- 10074183
TI  - Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated
      human immunodeficiency virus type 1 vaccines in Rhesus macaques: evidence for
      viral clearance.
AB  - The kinetics of T-helper immune responses generated in 16 mature outbred rhesus
      monkeys (Macaca mulatta) within a 10-month period by three different human
      immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune
      responses to monomeric recombinant gp120SF2 (rgp120) when the protein was
      expressed in vivo by DNA immunization or when it was delivered as a subunit
      protein vaccine formulated either with the MF59 adjuvant or by incorporation into
      immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing
      antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2
      protein-immunized groups, but the responses showed different kinetics, while NA
      were delayed and their levels were low in the DNA-immunized animals. Antigen
      specific gamma interferon (IFN-gamma) T-helper (type 1-like) responses were
      detected in the DNA-immunized group, but only after the fourth immunization, and
      the rgp120/MF59 group generated both IFN-gamma and interleukin-4 (IL-4) (type 2
      like) responses that appeared after the third immunization. In contrast,
      rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-gamma (type 1
      like), and IL-4 responses that peaked after the second immunization. To determine
      which type of immune responses correlated with protection from infection, all
      animals were challenged intravenously with 50 50% infective doses of a rhesus
      cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency
      virus-HIVSF13 construct. Protection was observed in the two groups receiving the
      rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely
      protected from infection. In other subunit vaccinees there was evidence by
      multiple assays that virus detected at 2 weeks postchallenge was effectively
      cleared. Early induction of potent type 1- as well as type 2-like T-helper
      responses induced the most-effective immunity.

PMID- 10074184
TI  - ERV-L elements: a family of endogenous retrovirus-like elements active throughout
      the evolution of mammals.
AB  - We have previously identified in the human genome a family of 200 endogenous
      retrovirus-like elements, the HERV-L elements, disclosing similarities with the
      foamy retroviruses and which might be the evolutionary intermediate between
      classical intracellular retrotransposons and infectious retroviruses. Southern
      blot analysis of a large series of mammalian genomic DNAs shows that HERV-L
      related elements-so-called ERV-L-are present among all placental mammals,
      suggesting that ERV-L elements were already present at least 70 million years
      ago. Most species exhibit a low copy number of ERV-L elements (from 10 to 30),
      while simians (not prosimians) and mice (not rats) have been subjected to bursts
      resulting in increases in the number of copies up to 200. The burst of copy
      number in primates can be dated to shortly after the prosimian and simian
      branchpoint, 45 to 65 million years ago, whereas murine species have been
      subjected to two much more recent bursts (less than 10 million years ago),
      occurring after the Mus/Rattus split. We have amplified and sequenced 360-bp ERV
      L internal fragments of the highly conserved pol gene from a series of 22
      mammalian species. These sequences exhibit high percentages of identity (57 to
      99%) with the murine fully coding MuERV-L element. Phylogenetic analyses allowed
      the establishment of a plausible evolutionary scheme for ERV-L elements, which
      accounts for the high level of sequence conservation and the widespread
      dispersion among mammals.

PMID- 10074185
TI  - Irreversible inhibition of human immunodeficiency virus type 1 integrase by
      dicaffeoylquinic acids.
AB  - Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require
      integration of a double-stranded DNA copy of the RNA genome into the host cell
      chromosome for productive infection. The viral enzyme, integrase, catalyzes the
      integration of retroviral DNA and represents an attractive target for developing
      antiretroviral agents. We identified several derivatives of dicaffeoylquinic
      acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic
      activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit
      the integration in vitro and the mechanism of inhibition were examined in the
      present study. Titration experiments with different concentrations of HIV-1
      integrase or DNA substrate found that the effect of DCQAs was exerted on the
      enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro
      activities of MLV integrase and truncated variants of feline immunodeficiency
      virus integrase, suggesting that these compounds interacted with the central core
      domain of integrase. The inhibition on retroviral integrases was relatively
      specific, and DCQAs had no effect on several other DNA-modifying enzymes and
      phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the
      inhibition of integrase by DCQAs was irreversible. The inhibition did not require
      the presence of a divalent cation and was unaffected by preassembling integrase
      onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on
      integrase is directed toward conserved amino acid residues in the central core
      domain during catalysis.

PMID- 10074186
TI  - Long-term follow-up of chimpanzees inoculated with the first infectious clone for
      hepatitis C virus.
AB  - Two chimpanzees (Ch1535 and Ch1536) became infected with hepatitis C virus (HCV)
      following intrahepatic inoculation with RNA transcribed from a full-length cDNA
      clone of the virus. Both animals were persistently infected and have been
      followed for 60 weeks. They showed similar responses to infection, with transient
      liver enzyme elevations and liver inflammatory responses, which peaked at weeks
      17 (Ch1535) and 12 (Ch1536) postinoculation (p.i.). Antibody responses to
      structural and nonstructural proteins were first detected at weeks 13 (Ch1535)
      and 10 (Ch1536) p.i. Serum RNA titers increased steadily during the first 10 to
      13 weeks but decreased sharply in both animals following antibody and
      inflammatory responses. Despite direct evidence of humoral immune responses to
      multiple viral antigens, including hypervariable region 1 (HVR1), both animals
      remained chronically infected. Detailed sequence analysis of serum HCV RNA
      revealed no change in the majority HVR1 sequence in Ch1535 and a single-amino
      acid mutation in Ch1536, with very little clonal variation in either animal. Full
      length genome analysis at week 60 revealed several amino acid substitutions
      localized to antigens E1, E2, p7, NS3, and NS5. Of these, 55.6 and 40% were
      present as the majority sequence in serum RNA isolated at week 26 p.i. (Ch1535)
      and week 22 p.i. (Ch1536), respectively, and could represent immune escape
      mutations. Mutations accumulated at a rate of 1.57 x 10(-3) and 1.48 x 10(-3)
      nucleotide substitutions/site/year for Ch1535 and Ch1536, respectively. Taken
      together, these data indicate that establishment of a persistent HCV infection in
      these chimpanzees is not due to changes in HVR1; however, the possibility remains
      that mutations arising in other parts of the genome contributed to this
      persistence.

PMID- 10074187
TI  - Persistent infection of human oligodendrocytic and neuroglial cell lines by human
      coronavirus 229E.
AB  - Human coronaviruses (HuCV) cause common colds. Previous reports suggest that
      these infectious agents may be neurotropic in humans, as they are for some
      mammals. With the long-term aim of providing experimental evidence for the
      neurotropism of HuCV and the establishment of persistent infections in the
      nervous system, we have evaluated the susceptibility of various human neural cell
      lines to acute and persistent infection by HuCV-229E. Viral antigen, infectious
      virus progeny and viral RNA were monitored during both acute and persistent
      infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as
      neuroblastoma SK-N-SH, neuroglioma H4, and oligodendrocytic MO3.13 cell lines,
      were all susceptible to an acute infection by HuCV-229E. The CHME-5 immortalized
      fetal microglial cell line was not susceptible to infection by this virus. The
      MO3.13 and H4 cell lines also sustained a persistent viral infection, as
      monitored by detection of viral antigen and infectious virus progeny. Sequencing
      of the S1 gene from viral RNA after approximately 130 days of infection showed
      two point mutations, suggesting amino acid changes during persistent infection of
      MO3.13 cells but none for H4 cells. Thus, persistent in vitro infection did not
      generate important changes in the S1 portion of the viral spike protein, which
      was shown for murine coronaviruses to bear hypervariable domains and to interact
      with cellular receptor. These results are consistent with the potential
      persistence of HuCV-229E in cells of the human nervous system, such as
      oligodendrocytes and possibly neurons, and the virus's apparent genomic
      stability.

PMID- 10074188
TI  - Acute and persistent infection of human neural cell lines by human coronavirus
      OC43.
AB  - Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated
      by different laboratories suggest their neurotropic potential. For example,
      primary cultures of human astrocytes and microglia were shown to be susceptible
      to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong,
      and P. J. Talbot, J. Virol. 71:800-806, 1997). We speculate that the neurotropism
      of HuCV will lead to persistence within the central nervous system, as was
      observed for murine coronaviruses. As a first step in the verification of our
      hypothesis, we have characterized the susceptibility of various human neural cell
      lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and
      viral RNA were monitored during both acute and persistent infections. The
      astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK
      N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal
      microglial cell lines, were all susceptible to an acute infection by HuCV-OC43.
      Viral antigen and RNA and release of infectious virions were observed during
      persistent HuCV-OC43 infections ( approximately 130 days of culture) of U-87 MG,
      U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the
      putatively hypervariable viral S1 gene fragment obtained after 130 days of
      culture were compared to that of initial virus input. Point mutations leading to
      amino acid changes were observed in all persistently infected cell lines.
      Moreover, an in-frame deletion was also observed in persistently infected H4
      cells. Some point mutations were observed in some molecular clones but not all,
      suggesting evolution of the viral population and the emergence of viral
      quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines.
      These results are consistent with the potential persistence of HuCV-OC43 in cells
      of the human nervous system, accompanied by the production of infectious virions
      and molecular variation of viral genomic RNA.

PMID- 10074189
TI  - Mutations in the carboxyl-terminal domain of the small hepatitis B virus envelope
      protein impair the assembly of hepatitis delta virus particles.
AB  - The carboxyl-terminal domain of the small (S) envelope protein of hepatitis B
      virus was subjected to mutagenesis to identify sequences important for the
      envelopment of the nucleocapsid during morphogenesis of hepatitis delta virus
      (HDV) virions. The mutations consisted of carboxyl-terminal truncations of 4 to
      64 amino acid residues and small combined deletions and insertions spanning the
      entire hydrophobic domain between residues 163 and 224. Truncation of as few as
      14 residues partially inhibited glycosylation and secretion of S and prevented
      assembly or stability of HDV virions. Short internal combined deletions and
      insertions were tolerated for secretion of subviral particles with the exceptions
      of those affecting residues 164 to 173 and 219 to 223. However, mutants competent
      for subviral particle secretion had a reduced capacity for HDV assembly compared
      to that of the wild type. One exception was a mutant carrying a deletion of
      residues 214 to 218, which exhibited a twofold increase in HDV assembly (or
      stability), whereas deletions of residues 179 to 183, 194 to 198, and 199 to 203
      were the most inhibitory. Substitutions of single amino acids between residues
      194 and 198 demonstrated that HDV assembly deficiency could be assigned to the
      replacement of the tryptophan residue at position 196. We concluded that assembly
      of stable HDV particles requires a specific function of the carboxyl terminus of
      S which is mediated at least in part by Trp-196.

PMID- 10074190
TI  - Late domain function identified in the vesicular stomatitis virus M protein by
      use of rhabdovirus-retrovirus chimeras.
AB  - Little is known about the mechanisms used by enveloped viruses to separate
      themselves from the cell surface at the final step of budding. However, small
      sequences in the Gag proteins of several retroviruses (L domains) have been
      implicated in this process. A sequence has been identified in the M proteins of
      rhabdoviruses that closely resembles the PPPPY motif in the L domain of Rous
      sarcoma virus (RSV), an avian retrovirus. To evaluate whether the PPPY sequence
      in vesicular stomatitis virus (VSV) M protein has an activity analogous to that
      of the retroviral sequence, M-Gag chimeras were characterized. The N-terminal 74
      amino acids of the VSV (Indiana) M protein, including the PPPY motif, was able to
      replace the L domain of RSV Gag and allow the assembly and release of virus-like
      particles. Alanine substitutions in the VSV PPPY motif severely compromised the
      budding activity of this hybrid protein but not that of another chimera which
      also contained the RSV PPPPY sequence. We conclude that this VSV sequence is
      functionally homologous to the RSV L domain in promoting virus particle release,
      making this the first example of such an activity in a virus other than a
      retrovirus. Both the RSV and VSV motifs have been shown to interact in vitro with
      certain cellular proteins that contain a WW interaction module, suggesting that
      the L domains are sites of interaction with unknown host machinery involved in
      virus release.

PMID- 10074191
TI  - Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong.
AB  - The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong
      in 1997 was transmitted directly from poultry to humans. Viral isolates from this
      outbreak may provide molecular clues to zoonotic transfer. Here we demonstrate
      that the H5N1 viruses circulating in poultry comprised two distinguishable
      phylogenetic lineages in all genes that were in very rapid evolution. When
      introduced into new hosts, influenza viruses usually undergo rapid alteration of
      their surface glycoproteins, especially in the hemagglutinin (HA). Surprisingly,
      these H5N1 isolates had a large proportion of amino acid changes in all gene
      products except in the HA. These viruses maybe reassortants each of whose HA gene
      is well adapted to domestic poultry while the rest of the genome arises from a
      different source. The consensus amino acid sequences of "internal" virion
      proteins reveal amino acids previously found in human strains. These human
      specific amino acids may be important factors in zoonotic transmission.

PMID- 10074192
TI  - A herpesvirus ribosome-associated, RNA-binding protein confers a growth advantage
      upon mutants deficient in a GADD34-related function.
AB  - The herpes simplex virus type 1 gamma34.5 gene product and the cellular GADD34
      protein both contain similar domains that can regulate the activity of eukaryotic
      initiation factor 2 (eIF2), a critical translation initiation factor. Viral
      mutants that lack the GADD34-related function grow poorly on a variety of
      malignant human cells, as activation of the cellular PKR kinase leads to the
      accumulation of inactive, phosphorylated eIF2 at late times postinfection.
      Termination of translation prior to the completion of the viral reproductive
      cycle leads to impaired growth. Extragenic suppressors that regain the ability to
      synthesize proteins efficiently in the absence of the viral GADD34-related
      function have been isolated. These suppressor alleles are dominant in trans and
      affect the steady-state accumulation of several viral mRNA species. We
      demonstrate that deregulated expression of Us11, a virus-encoded RNA-binding,
      ribosome-associated protein is necessary and sufficient to confer a growth
      advantage upon viral mutants that lack a GADD34-related function. Ectopic
      expression of Us11 reduces the accumulation of the activated cellular PKR kinase
      and allows for sustained protein synthesis. Thus, an RNA-binding, ribosome
      associated protein (Us11) and a GADD34-related protein (gamma34.5) both function
      in a signal pathway that regulates translation by modulating eIF2
      phosphorylation.

PMID- 10074193
TI  - Mutagenic analysis of the 3' cis-acting elements of the rubella virus genome.
AB  - Thermodynamically predicted secondary structure analysis of the 3'-terminal 305
      nucleotides (nt) of the rubella virus (RUB) genome, a region conserved in all RUB
      defective interfering RNAs, revealed four stem-loop (SL) structures; SL1 and SL2
      are both located in the E1 coding region, while SL3 and SL4 are within the 59-nt
      3' untranslated region (UTR) preceding the poly(A) tract. SL2 is a structure
      shown to interact with human calreticulin (CAL), an autoantigen potentially
      involved in RUB RNA replication and pathogenesis. RNase mapping indicated that
      SL2 and SL3 are in equilibrium between two conformations, in the second of which
      the previously proposed CAL binding site in SL2, a U-U bulge, is not formed. Site
      directed mutagenesis of the 3' UTR with a RUB infectious clone, Robo302, revealed
      that most of the 3' UTR is required for viral viability except for the 3'
      terminal 5 nt and the poly(A) tract, although poly(A) was rapidly regenerated
      during subsequent replication. Maintenance of the overall SL3 structure, the 11
      nt single-stranded sequence between SL3 and SL4, and the sequences forming SL4
      were all important for viral viability. Studies on the interaction between host
      factors and the 3' UTR showed the formation of three RNA-protein complexes by gel
      mobility shift assay, and UV-induced cross-linking detected six host protein
      species, with molecular masses of 120, 80, 66, 55, 48, and 36 kDa, interacting
      with the 3' UTR. Site-directed mutagenesis of SL2 by nucleotide substitutions
      showed that maintenance of SL2 stem rather than the U-U bulge was critical in CAL
      binding since mutants having the U-U bulge base paired had a similar binding
      activity for CAL as the native structure whereas mutants having the SL2 stem
      destabilized had much lower binding activity. However, all of these mutations
      gave rise to viable viruses when introduced into Robo302, indicating that binding
      of CAL to SL2 is independent of viral viability.

PMID- 10074194
TI  - Activation of baculovirus very late promoters by interaction with very late
      factor 1.
AB  - Very late factor 1 (VLF-1) of Autographa californica multicapsid nuclear
      polyhedrosis virus (AcMNPV) activates the transcription of two genes, polyhedrin
      (polh) and p10, during the final, occlusion-specific phase of infection. Using
      transient expression assays responsive to VLF-1, we identified linker scan
      mutations in the polh and p10 promoters which abolished or weakened the ability
      of the promoters to respond to stimulation by VLF-1. These mutations were located
      between the transcriptional and translational initiation sites, a region
      previously shown to be essential for the burst of expression during the very late
      phase. Addition of partially purified, epitope-tagged VLF-1 to DNA encompassing
      this "burst sequence" resulted in a shift in the gel electrophoretic mobility of
      the DNA, indicating that VLF-1 forms a complex with DNA. Addition of an antibody
      specific for the epitope tag of VLF-1 decreased the mobility of the DNA further,
      confirming the presence of VLF-1 in the complex. DNase I footprint assays
      revealed that VLF-1 partially purified from either insect cells or bacterial
      cells interacted with the burst sequences of both the polh and p10 very-late
      promoters. Linker scan mutations within the burst sequences severely impaired
      interaction between VLF-1 and the promoters. We propose that VLF-1 transactivates
      the polh and p10 promoters by interacting with the burst sequences.

PMID- 10074195
TI  - Disease-inducible transgene expression from a recombinant adeno-associated virus
      vector in a rat arthritis model.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 1% of the
      world's population, with significant morbidity and mortality. In this study, we
      investigated a recombinant adeno-associated virus (rAAV) vector for its potential
      application in RA gene therapy. rAAV encoding Escherichia coli beta-galactosidase
      was injected into rat joints which had already been induced into acute arthritis
      after local lipopolysaccharide (LPS) administration, and the efficiency of in
      vivo transduction was evaluated. We observed a striking correlation between
      vector transgene expression and disease severity in arthritic joints. The
      inflammatory reaction peaked at 3 to 7 days after LPS treatment, and, at the same
      time, 95% of the synoviocytes had high-level transgene expression. Gene
      expression diminished to the basal level (5%) when the inflammation subsided at
      30 days after LPS treatment. More importantly, the diminished transgene
      expression could be efficiently reactivated by a repeated insult. The transgene
      expression in normal joints transduced with rAAV remained low for a long period
      of time (30 days) but could still be induced to high levels (95%) at 3 to 7 days
      after LPS treatment. This is the first demonstration of disease state-regulated
      transgene expression. These findings strongly support the feasibility of
      therapeutic as well as preventative gene transfer approaches for RA with rAAV
      vectors containing therapeutic genes, which are expected to respond primarily to
      the disease state of the target tissue.

PMID- 10074196
TI  - Role for gamma interferon in control of herpes simplex virus type 1 reactivation.
AB  - Observation of chronic inflammatory cells and associated high-level gamma
      interferon (IFN-gamma) production in ganglia during herpes simplex type 1 (HSV-1)
      latent infection in mice (E. M. Cantin, D. R. Hinton, J. Chen, and H. Openshaw,
      J. Virol. 69:4898-4905, 1995) prompted studies to determine a role of IFN-gamma
      in maintaining latency. Mice lacking IFN-gamma (GKO mice) or the IFN-gamma
      receptor (RGKO mice) were inoculated with HSV-1, and the course of the infection
      was compared with that in IFN-gamma-competent mice with the same genetic
      background (129/Sv//Ev mice). A time course study showed no significant
      difference in trigeminal ganglionic viral titers or the timing of establishment
      of latency. Spontaneous reactivation resulting in infectious virus in the
      ganglion did not occur during latency in any of the mice. However, 24 h after the
      application of hyperthermic stress to mice, HSV-1 antigens were detected in
      multiple neurons in the null mutant mice but in only a single neuron in the
      129/Sv//Ev control mice. Mononuclear inflammatory cells clustered tightly around
      these reactivating neurons, and by 48 h, immunostaining was present in satellite
      cells as well. The incidence of hyperthermia-induced reactivation as determined
      by recovery of infectious virus from ganglia was significantly higher in the null
      mutant than in control mice: 11% in 129/Sv//Ev controls, 50% in GKO mice (P =
      0.0002), and 33% in RGKO mice (P = 0.03). We concluded that IFN-gamma is not
      involved in the induction of reactivation but rather contributes to rapid
      suppression of HSV once it is reactivated.

PMID- 10074197
TI  - Systemic and central nervous system correction of lysosomal storage in
      mucopolysaccharidosis type VII mice.
AB  - Mucopolysaccharidosis (MPS) type VII patients lack functional beta-glucuronidase,
      leading to systemic and central nervous system dysfunction. In this study we
      tested whether recombinant adenovirus that encodes beta-glucuronidase
      (Adbetagluc), delivered intravenously and into the brain parenchyma of MPS type
      VII mice, could provide long-term transgene expression and correction of
      lysosomal distension. We also tested whether systemic treatment with the
      immunosuppressive anti-CD40 ligand antibody, MR-1, affected transgene expression.
      We found substantial plasma beta-glucuronidase activity for over 9 weeks after
      gene transfer in the MR-1- treated group, with subsequent decline in activity
      corresponding to a delayed anti-beta-glucuronidase antibody response. At 16
      weeks, near wild-type amounts of beta-glucuronidase activity and striking
      reduction of lysosomal pathology were detected in livers from mice that had
      received either MR-1 cotreatment or control antibody. In the lung and kidney,
      beta-glucuronidase activity was markedly higher for the MR-1-treated group. beta
      Glucuronidase activity in the brain persisted independently of MR-1 treatment.
      Activity was intense in the injected hemisphere and was also evident in the
      noninjected cortex and striatum, with dramatic improvements in storage deposits
      in areas of both hemispheres. These results indicate that prolonged enzyme
      expression from transgenes delivered to deficient liver and brain can mediate
      pervasive correction and illustrate the potential for gene therapy of MPS and
      other lysosomal storage diseases.

PMID- 10074198
TI  - The equine herpesvirus 1 Us2 homolog encodes a nonessential membrane-associated
      virion component.
AB  - Experiments were conducted to analyze the equine herpesvirus 1 (EHV-1) gene 68
      product which is encoded by the EHV-1 Us2 homolog. An antiserum directed against
      the amino-terminal 206 amino acids of the EHV-1 Us2 protein specifically detected
      a protein with an Mr of 34,000 in cells infected with EHV-1 strain RacL11. EHV-1
      strain Ab4 encodes a 44,000-Mr Us2 protein, whereas vaccine strain RacH, a high
      passage derivative of RacL11, encodes a 31,000-Mr Us2 polypeptide. Irrespective
      of its size, the Us2 protein was incorporated into virions. The EHV-1 Us2 protein
      localized to membrane and nuclear fractions of RacL11-infected cells and to the
      envelope fraction of purified virions. To monitor intracellular trafficking of
      the protein, the green fluorescent protein (GFP) was fused to the carboxy
      terminus of the EHV-1 Us2 protein or to a truncated Us2 protein lacking a stretch
      of 16 hydrophobic amino acids at the extreme amino terminus. Both fusion proteins
      were detected at the plasma membrane and accumulated in the vicinity of nuclei of
      transfected cells. However, trafficking of either GFP fusion protein through the
      secretory pathway could not be demonstrated, and the EHV-1 Us2 protein lacked
      detectable N- and O-linked carbohydrates. Consistent with the presence of the Us2
      protein in the viral envelope and plasma membrane of infected cells, a Us2
      negative RacL11 mutant (L11DeltaUs2) exhibited delayed penetration kinetics and
      produced smaller plaques compared with either wild-type RacL11 or a Us2-repaired
      virus. After infection of BALB/c mice with L11DeltaUs2, reduced pathogenicity
      compared with the parental RacL11 virus and the repaired virus was observed. It
      is concluded that the EHV-1 Us2 protein modulates virus entry and cell-to-cell
      spread and appears to support sustained EHV-1 replication in vivo.

PMID- 10074199
TI  - Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or
      SH gene is attenuated in chimpanzees.
AB  - The NS2 and SH genes of respiratory syncytial virus (RSV) have been separately
      deleted from a recombinant wild-type RSV strain, A2 (M. N. Teng and P. L.
      Collins, J. Virol. 73:466-473, 1998; A. Bukreyev et al., J. Virol. 71:8973-8982,
      1997; and this study). The resulting viruses, designated rA2DeltaNS2 and
      rA2DeltaSH, were administered to chimpanzees to evaluate their levels of
      attenuation and immunogenicity. Recombinant virus rA2DeltaNS2 replicated to
      moderate levels in the upper respiratory tract, was highly attenuated in the
      lower respiratory tract, and induced significant resistance to challenge with
      wild-type RSV. The replication of rA2DeltaSH virus was only moderately reduced in
      the lower, but not the upper, respiratory tract. However, chimpanzees infected
      with either virus developed significantly less rhinorrhea than those infected
      with wild-type RSV. These findings demonstrate that a recombinant RSV mutant
      lacking either the NS2 or SH gene is attenuated and indicate that these deletions
      may be useful as attenuating mutations in new, live recombinant RSV vaccine
      candidates for both pediatric and elderly populations. The DeltaSH mutation was
      incorporated into a recombinant form of the cpts248/404 vaccine candidate, was
      evaluated for safety in seronegative chimpanzees, and can now be evaluated as a
      vaccine for humans.

PMID- 10074200
TI  - Will multiple coreceptors need to be targeted by inhibitors of human
      immunodeficiency virus type 1 entry?
AB  - Despite being able to use the Bonzo coreceptor as efficiently as CCR5 in
      transfected cells, pediatric human immunodeficiency virus type 1 isolate P6 was
      unable to replicate in peripheral blood mononuclear cells (PBMC) lacking the CCR5
      receptor. Furthermore, its replication in wild-type PBMC was completely inhibited
      by inhibitors of CCR5-mediated entry. Similarly, maternal isolate M6 could use
      CCR5, CXCR4, Bonzo, and other coreceptors in transfected cells but was completely
      sensitive to inhibitors of CCR5- and CXCR4-mediated entry when grown in PBMC. The
      ability of these viruses to use coreceptors in addition to CCR5 and CXCR4 in
      vitro was, therefore, irrelevant to their drug sensitivity in primary cells. We
      argue that CCR5 and CXCR4 should remain the primary targets for antiviral drug
      development, pending strong evidence to the contrary.

PMID- 10074201
TI  - Human immunodeficiency virus type 1 derived from cocultures of immature dendritic
      cells with autologous T cells carries T-cell-specific molecules on its surface
      and is highly infectious.
AB  - During the budding process, human immunodeficiency virus type 1 (HIV-1) acquires
      cell surface molecules; thus, the viral surface of HIV-1 reflects the antigenic
      pattern of the host cell. To determine the source of HIV-1 released from
      cocultures of dendritic cells (DC) with T cells, immature DC (imDC), mature DC
      (mDC), T cells, and their cocultures were infected with different HIV-1 isolates.
      The macrophage-tropic HIV-1 isolate Ba-L allowed viral replication in both imDC
      and mDC, whereas the T-cell-line-tropic primary isolate PI21 replicated in mDC
      only. By a virus capture assay, HIV-1 was shown to carry a T-cell- or DC-specific
      cell surface pattern after production by T cells or DC, respectively. Upon
      cocultivation of HIV-1-pulsed DC with T cells, HIV-1 exclusively displayed a
      typical T-cell pattern. Additionally, functional analysis revealed that HIV-1
      released from imDC-T-cell cocultures was more infectious than HIV-1 derived from
      mDC-T-cell cocultures and from cultures of DC, T cells, or peripheral blood
      mononuclear cells alone. Therefore, we conclude that the interaction of HIV-1
      pulsed imDC with T cells in vivo might generate highly infectious virus which
      primarily originates from T cells.

PMID- 10074202
TI  - Effects of human immunodeficiency virus type 1 resistance to protease inhibitors
      on reverse transcriptase processing, activity, and drug sensitivity.
AB  - Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease
      inhibitors often display a reduced replicative capacity as a result of an
      impairment of protease function. Such fitness-impaired viruses display Gag
      precursor maturation defects. Here, we report that some protease inhibitor
      resistant viruses also display abnormalities in the processing of reverse
      transcriptase (RT) by the protease. In three recombinant viruses carrying
      resistant protease sequences from patient plasma, we observed a marked decrease
      in the amount of mature RT subunits and of particle-associated RT activity
      compared to their parental pretherapy counterparts. We investigated the
      possibility that a decrease in the amount of particle-associated mature RT could
      affect the sensitivity of the corresponding virus to RT inhibitors. We observed a
      twofold increase of sensitivity to zidovudine (AZT) when a virus which carried
      AZT mutations was processed by a resistant protease. Interestingly, the presence
      of AZT-resistance mutations partially rescued the replication defect associated
      with the mutated protease. The interplay between resistance to protease
      inhibitors and to RT inhibitors described here may be relevant to the therapeutic
      control of HIV-1 infection.

PMID- 10074203
TI  - Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen
      activated protein kinase signaling pathway.
AB  - ERK1 and ERK2 mitogen-activated protein kinases (MAPK) play a critical role in
      regulation of cell proliferation and differentiation in response to mitogens and
      other extracellular stimuli. Mitogens and cytokines that activate MAPK in T cells
      have been shown to activate human immunodeficiency virus type 1 (HIV-1)
      replication. Little is known about the signal transduction pathways that activate
      HIV-1 replication in T cells upon activation by extracellular stimulation. Here,
      we report that activation of MAPK through the Ras/Raf/MEK signaling pathway
      enhances the infectivity of HIV-1 virions. Virus infectivity was enhanced by
      treatment of cells with MAPK stimulators, such as serum and phorbol myristate
      acetate, as well as by coexpression of constitutively activated Ras, Raf, or MEK
      (MAPK kinase) in the absence of extracellular stimulation. Treatment of cells
      with PD 098059, a specific inhibitor of MAPK activation, or with a MAPK antisense
      oligonucleotide reduced the infectivity of HIV-1 virions without significantly
      affecting virus production or the levels of virion-associated Gag and Env
      proteins. MAPK has been shown to regulate HIV-1 infectivity by phosphorylating
      Vif (X. Yang and D. Gabuzda, J. Biol. Chem. 273:29879-29887, 1998). However, MAPK
      activation enhanced virus infectivity in some cells lines that do not require Vif
      function. The HIV-1 Rev, Tat, p17(Gag), and Nef proteins were directly
      phosphorylated by MAPK in vitro, suggesting that other HIV-1 proteins are
      potential substrates for MAPK phosphorylation. These results suggest that
      activation of the ERK MAPK pathway plays a role in HIV-1 replication by enhancing
      the infectivity of HIV-1 virions through Vif-dependent as well as Vif-independent
      mechanisms. MAPK activation in producer cells may contribute to the activation of
      HIV-1 replication when T cells are activated by mitogens and other extracellular
      stimuli.

PMID- 10074204
TI  - Eukaryotic initiation factor 4GII (eIF4GII), but not eIF4GI, cleavage correlates
      with inhibition of host cell protein synthesis after human rhinovirus infection.
AB  - For many members of the Picornaviridae family, infection of cells results in a
      shutoff of host protein synthesis. For rhinoviruses and enteroviruses, the
      shutoff has been explained in part by the cleavage of eukaryotic initiation
      factor 4GI (eIF4GI), a component of the cap-binding protein complex eIF4F. The
      cleavage of eIF4GI is mediated by the virus-specific proteinase 2Apro and results
      in inhibition of cap-dependent, but not cap-independent, translation. The
      inhibition of host protein synthesis after infection with human rhinovirus 14
      (HRV-14) lags behind the cleavage of eIF4GI. Recently, we discovered a functional
      homolog of eIF4GI, termed eIF4GII, and showed that cleavage of eIF4GII coincides
      with the shutoff of host cell protein synthesis after poliovirus infection (Gradi
      et al., Proc. Natl. Acad. Sci. USA 95:11089-11094, 1998). We wished to determine
      whether eIF4GII cleavage kinetics could also explain the lack of correlation
      between the kinetics of eIF4GI cleavage and the shutoff of host protein synthesis
      after rhinovirus infection. In this study, we examined the correlation between
      human rhinovirus-induced shutoff of host protein synthesis and cleavage of eIF4GI
      and eIF4GII. In HRV-14-infected HeLa cells, almost no intact eIF4GI could be
      detected by 4 h postinfection, while only 4% of eIF4GII was cleaved at this time.
      By 6 h, however, 67% of eIF4GII was cleaved, and this cleavage coincided with a
      significant (60%) decline of host translation. These results suggest that
      cleavage of both eIF4GI and eIF4GII is required for HRV-mediated inhibition of
      host cell protein synthesis and that the cleavage of eIF4GII is the rate-limiting
      step in the shutoff of host cell protein synthesis after rhinovirus infection.

PMID- 10074205
TI  - Direct evidence that the poly(A) tail of influenza A virus mRNA is synthesized by
      reiterative copying of a U track in the virion RNA template.
AB  - The poly(A) tail of influenza virus mRNA is thought to be synthesized by
      reiterative copying of the U track near the 5' end of the virion RNA template.
      This has been widely accepted as a plausible hypothesis, but until now there has
      been no direct experimental evidence for it. Here, we report such direct evidence
      based on the fact that (i) replacing the U track with an A track directs
      synthesis of products with poly(U) tails, both in vitro and in vivo, and (ii)
      interrupting the U track abolishes polyadenylation in vitro.

PMID- 10074206
TI  - R region sequences in the long terminal repeat of a murine retrovirus
      specifically increase expression of unspliced RNAs.
AB  - A stem-loop structure at the 5' end of the R region of the long terminal repeat
      (LTR) of the murine leukemia virus SL3 and other type C mammalian retroviruses is
      important for maximum levels of expression of a reporter gene under the control
      of the viral LTR. This element, termed the R region stem-loop (RSL), has a small
      effect on transcriptional initiation and no effect on RNA polymerase
      processivity. Its major effect is on posttranscriptional processing of LTR-driven
      transcripts. Here we tested whether the RSL affected the production of RNAs from
      a full-length SL3 genome. Mutation of the RSL in the 5' LTR of SL3 reduced the
      cytoplasmic levels of full-length viral transcripts but not those of spliced, env
      mRNA transcripts. Thus, the RSL specifically affected the cytoplasmic levels of
      the unspliced viral RNA. To test further whether the effect was specific for
      unspliced transcripts, a system was devised in which the expression of a reporter
      gene under the control of the viral LTR was tested in the presence or absence of
      an intron. Mutation of the RSL resulted in only about a twofold decline in the
      level of reporter gene expression when the transcripts contained an intron.
      However, when the intron was removed, mutation of the RSL reduced expression of
      the reporter gene about 10- to 60-fold in various cell lines. The secondary
      structure of the RSL was essential for its activity on the intronless transcript.
      Thus, the RSL appears to be important for the cytoplasmic accumulation of
      unspliced viral RNA and unspliced RNA from chimeric transcription units under the
      control of the viral LTR.

PMID- 10074207
TI  - Infectious pancreatic necrosis virus: identification of a VP3-containing
      ribonucleoprotein core structure and evidence for O-linked glycosylation of the
      capsid protein VP2.
AB  - Virions of infectious pancreatic necrosis virus (IPNV) were completely
      disintegrated upon dialysis against salt-free buffers. Direct visualization of
      such preparations by electron microscopy revealed 5.0- to 6.5-nm-thick entangled
      filaments. By using a specific colloidal gold immunolabeling technique, these
      structures were shown to contain the viral protein VP3. Isolation by sucrose
      gradient centrifugation of the filaments, followed by serological analysis,
      demonstrated that the entire VP3 content of the virion was recovered together
      with the radiolabeled genomic material forming the unique threadlike
      ribonucleoprotein complexes. In a sensitive blotting assay, the outer capsid
      component of IPNV, i.e., the major structural protein VP2, was shown to
      specifically bind lectins recognizing sugar moieties of N-acetylgalactosamine,
      mannose, and fucose. Three established metabolic inhibitors of N-linked
      glycosylation did not prevent addition of sugar residues to virions, and
      enzymatic deglycosylation of isolated virions using N-glycosidase failed to
      remove sugar residues of VP2 recognized by lectins. However, gentle alkaline beta
      elimination clearly reduced the ability of lectins to recognize VP2. These
      results suggest that the glycosylation of VP2 is of the O-linked type when IPNV
      is propagated in RTG-2 cells.

PMID- 10074208
TI  - Ebola virus selectively inhibits responses to interferons, but not to interleukin
      1beta, in endothelial cells.
AB  - Ebola virus infection is highly lethal and leads to severe immunosuppression. In
      this study, we demonstrate that infection of human umbilical vein endothelial
      cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expression of the
      major histocompatibility complex class I (MHC I) family of proteins and inhibited
      the induction of multiple genes by alpha interferon (IFN-alpha) and IFN-gamma,
      including those coding for MHC I proteins, 2'-5' oligoadenylate synthetase [2'
      5'(A)N], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6)
      and ICAM-1 by IL-1beta was not suppressed by infection with EZ, suggesting that
      the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that
      infection with EZ blocked the induction by IFNs of nuclear proteins that bind to
      IFN-stimulated response elements, gamma activation sequences, and IFN regulatory
      factor binding site (IRF-E). In contrast, infection with EZ did not block
      activation of the transcription factor NF-kappaB by IL-1beta. The events that
      lead to the blockage of IFN signaling may be critical for Ebola virus-induced
      immunosuppression and would play a role in the pathogenesis of Ebola virus
      infection.

PMID- 10074210
TI  - Two novel promoters in the upstream regulatory region of human papillomavirus
      type 31b are negatively regulated by epithelial differentiation.
AB  - Organotypic cultures support the stratification and differentiation of
      keratinocytes and the human papillomavirus (HPV) life cycle. We report
      transcription from four novel promoters in the HPV31b upstream regulatory region
      during the viral life cycle in organotypic cultures. Promoter initiation was not
      differentiation dependent; two promoters were down-regulated upon epithelial
      differentiation.

PMID- 10074209
TI  - Distinct human immunodeficiency virus strains in the bone marrow are associated
      with the development of thrombocytopenia.
AB  - We analyzed bone marrow and blood from human immunodeficiency virus type 1 (HIV
      1)-infected individuals and described the HIV-1 quasispecies in these cellular
      compartments. HIV-1 isolates from the bone marrow of thrombocytopenic patients
      contained distinct amino acids in the V3 loop and infected T-cell lines,
      implicating this virus in the development of thrombocytopenia.

PMID- 10074211
TI  - Effectiveness of polyene antibiotics in treatment of transmissible spongiform
      encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons.
AB  - To date very few drugs have favorably influenced the course of transmissible
      spongiform encephalopathies. In previous studies, the polyene antibiotics
      amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters
      of the 263K strain of scrapie, but AmB had no effect against other scrapie
      strains in Syrian hamsters. In the present experiments using transgenic mice
      expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of
      animals infected with the 263K strain but not the DY strain. AmB was effective
      against both 263K and DY and prevented death in 18% of DY-infected animals. The
      AmB effect against strain 263K was more prominent in mice whose endogenous PrP
      gene had been inactivated by homologous recombination. It was unclear whether
      this difference was due to a change in the duration of the disease or to possible
      interactive effects between the mouse PrP gene and the drugs themselves. The
      effectiveness of treatment after intracerebral scrapie infection in transgenic
      mice expressing PrP only in neurons suggested that neurons are important sites of
      action for these drugs.

PMID- 10074212
TI  - [Radioimmunoscintigraphy of colorectal cancer using the anti-CEA monoclonal
      antibody BW 431/26. Final results].
AB  - The anti-carcinoembryonic antigen (CEA) antibody, BW 431/26 (Scintimun CEA,
      Behringwerke, Marburg, Germany ) labeled with technetium pertechnectate (99mTc),
      is an intact immunoglobulin G1, monoclonal antibody that has been used to image
      colorectal cancer. Planar and SPECT images of chest, abdomen and pelvis were
      performed at 10 minutes, 4-6 and 18-24 hours after the intravenous antibody
      injection. 44 patients were studied and the pathological antibody concentration
      localization by radioimmunoimaging (RI) were correlated with surgical, clinical
      and other imaging modality findings to validate the RI. The RI was positive in 29
      patients and negative in the other 15 patients. The CEA and CA 19.9 were elevated
      in the serum of some patients with primary tumors or recurrence. The HAMA were
      determined in all the patients before and after the RI.

PMID- 10074213
TI  - [Radionuclide study of cutaneous melanomas with 99m Tc-HMPAO: visualization of
      metastases and recurrence].
AB  - Malignant cutaneous melanoma (MCM) is a very aggressive disease that becomes in a
      true problem of health because of the increase in the last 5 years. In the
      present paper, authors report the detection of the tumor, metastases and
      recurrences mean 99mTc HMPAO. We presented 5 cases of MCM patients and observed
      the radiopharmaceutical uptake in skin, nodules and recurrent tumor lesions.
      Because of the number of patients was limited, authors recommended the research
      with a lot of patients. The gammagraphic studies could be very important for the
      staging of the disease and early detection of metastases and recurrent lesions.

PMID- 10074214
TI  - Evaluation of the alveolar-capillary membrane permeability using 99mTc-HMPAO
      aerosols in severe diffuse interstitial fibrosis.
AB  - Local information on permeability of the alveolar-capillary barrier (PACB) can be
      ascertained by parametric images, after inhalation of radioarosols and computer
      processing. Our aim is to compare the results of 99mTc-HMPAO aerosols on PACB
      studies with those of 99mTc-DTPA aerosols, a standard technique. We compared the
      two techniques in separate samples: normal controls and patients with severe lung
      interstitial pathologies. Perfusion studies using 99mTc-MAA have also been
      performed in all patients. The aerosols were produced using ultrasound and
      lowered surface tension solution of 99mTc-HMPAO and 99mTc-DTPA. The time-activity
      curves (TACs) for every pixel on the lung area were used to calculate the half
      disappearance times (T1/2). Parametric images were then generated with those
      times. The comparison of the results obtained with 99mTc-HMPAO and 99mTc-DTPA
      aerosols suggests that the first ones are more specific for local alterations of
      the lung epithelial transport in the pathologies studied. This method
      distinguishes between permeability deficiency due to local perfusion decrease and
      ACB deterioration.

PMID- 10074215
TI  - [Valoration of the epidermal growth factor receptor (EGFR) in benign breast
      disease and its relation with expression in malignant tumors classified by
      hormonal dependence].
AB  - The aim of this work is studying the behaviour of EGFR in benign breast
      pathologies and correlating it to its expression in CDI with hormonal dependency
      or independency using a radioligand technique. The EGFR expression was higher in
      FAD rather than in MFQ (mean +/- S.D.: 13.7 +/- 13.5; range: 1.0-55.3; median:
      10.0 fmol/mg prot vs mean +/- S.D.: 4.0 +/- 3.5; range:1.0-11.4; median: 2.2
      fmol/mg prot), with a result of a positive correlation in the first ones with RP
      (r = 0.4557) but not with RE. FAD present similar EGFR concentrations to those in
      CDI-hormonal independents (mean +/- S.D.: 10.7 +/- 12.6; range: 1.0-60.2; median:
      6.75 fmol/mg prot), even though the way they are correlated with the content in
      RP leads us to the conclusion that they are both involved in the genesis and
      controled development of themselves. On the other hand, MFQ have got similar
      contents in EGFR to those of CDI hormono-dependents (mean +/- S.D.: 6.98 +/-
      15.72; range: 1.0-118; median: 2.55 fmol/mg prot); this fact proves that the
      development of this pathology does not only depend on the growth factors but also
      on the hormonal environment which influences it.

PMID- 10074216
TI  - [Radioisotopic localization of the sentinel lymph node in breast cancer.
      Preliminary results].
AB  - The aim of this preliminary work is to show the results of the radioisotopic
      localization of the sentinel node in breast cancer and the surgical resection
      using a gamma probe. We studied 10 patients with breast cancer without primary
      chemotherapy and 3 patients with primary chemotherapy before surgery. A
      lymphoscintigraphy was made after injection of 111 MBq of Tc99m-nanocolloid in a
      volume of 3 ml. The scans were performed after 30 minutes, 2 hours, 4 hours and
      24 hours after injection. We detected the node and then a skin mark was made. The
      next day, surgical resection of this node was performed, guided by a gamma probe.
      We detected all sentinel nodes but one: 12 sentinel nodes and 7 second echelon
      nodes. The mean time for a surgical detection was about 16 minutes. In our
      experience this technique allows an accurate localization of the sentinel node in
      patients with breast cancer. We are able to localize the node in the surgical
      room guided with gamma probe. The peroperatory evaluation by anatomopathological
      techniques shown the status of this node. All this, does not delay the surgical
      time.

PMID- 10074217
TI  - [Congenital cyanotic heart disease and peripheral neurogenic tumor].
AB  - The association between neuroblastic tumours and congenital heart disease is
      widely confirmed in the literature references. The authors describe a case of a
      patient with congenital heart disease, high blood pressure, renal artery stenosis
      and high levels in 24 hours urine metanephrines. A MIBG-I-123 scintigraphy was
      essential for the diagnosis of neuroblastic tumour.

PMID- 10074218
TI  - [Localization by bone SPET of osteoid osteoma in the vertebral lamina].
AB  - The combined use of bone SPET and CT was a good approach for diagnosing an
      osteoid osteoma of spine in a 16-year-old young woman with a history of several
      months of back pain. Pain was increased at night and relieved by aspirin intake.
      Plain films of the spine only revealed a scoliosis. Bone SPET demonstrated a
      focal increased activity in the left posterior elements of T12 vertebra. CT of
      this vertebra discovered a lytic lesion in the left lamina. An osteoid osteoma
      was removed by laminectomy.

PMID- 10074219
TI  - [PET-FDG in thyroid cancer with high thyroglobulin levels and negative 131-I
      scan. A case report].
AB  - The value of whole body PET-FDG in the evaluation of metastases has been
      demonstrated in a wide variety of tumors. In this report, we present the case of
      a patient with antecedent of papillary thyroid carcinoma, who was operated twelve
      years ago, and submitted to an ablative dose of residual thyroid tissue through
      131I, being the levels of thyroglobulin normals. After twelve years of evolution,
      the patient refers bag pain and respiratory trouble, appearing in the CT image
      suspicious of metastases in right pulmonary base. The levels of thyroglobulin
      were shown increased, being the 131I scan negative. A whole body PET-FDG study
      was performed in order to exclude metastases of his malignant process, showed
      multiple high FDG uptake focus in brain, cerebellum, neck, chest, lymphatic nodes
      and bone, suggestive of dedifferentiated disease These findings were confirmed
      subsequently in the clinic evolution. Therefore, whole-body PET-FDG is a
      complementary diagnostic technique for study patients with CDT (Thyroid
      Differentiated Carcinoma) with 131I scan negative and rising thyroglobulin
      levels.

PMID- 10074220
TI  - [Changes of [Ca2+]i in colorectal cancer cells induced by some chemicals].
AB  - Changes of [Ca2+]i in CCL229 cells induced by retionoic acid (RA), 1,25(OH)2VD3
      and PMA were measured by spectrofluorometry. The effects of endoplasmic reticulum
      (ER)-specific Ca(2+)-ATPase inhibitor thapsigargin (TG) and IP3 receptor
      inhibitor heparin on RA-induced changes of [Ca2+]i were observed and the
      relationship between RA-induced changes of [Ca2+]i and ER was also investigated.
      The results showed that [Ca2+]i increased markedly in several seconds after
      treated by RA and 1,25(OH)2VD3. When cells were pretreated with EGTA and
      verapamil (Ca2+ entry blocker drug), TG could not inhibit RA-stimulated Ca2+
      release from intracellular calcium pools and TG could increase [Ca2+]i after
      pretreated by RA. In addition, heparin could not completely inhibit RA-induced
      [Ca2+]i increase. The results suggest that RA might stimulate IP3-sensitive pool
      or IP3-insensitive pool on ER to increase [Ca2+]i, or there might be RA-sensitive
      calcium pools except ER in cells.

PMID- 10074221
TI  - [Effects of GABA on the development of embryonic mouse cerebro-cortical
      neurocytes and its mechanism].

PMID- 10074222
TI  - [The role of adenosine in the early stage of anoxia of hippocampal slices and its
      mechanisms].
AB  - The role of adenosine in reversible inhibition of synaptic function during the
      early stage of anoxia and its mechanisms were investigated with extracellular
      recording technique in rat hippocampal slices. The results showed that acute
      anoxia led to the reversible inhibition of synaptic function, which is similar to
      the response to addition of high concentration of exogenous adenosine. The
      reversible inhibition could be suppressed by adenosine A1 receptor antagonist CPT
      and potassium channel blocker 4-AP, whereas TEA and ATP-sensitive potassium
      channel blocker glipzide had no effect. These results suggest that during the
      early stage of anoxia, the enhanced release of endogenous adenosine can inhibit
      the synaptic transmission by activating 4-AP-sensitive potassium channels via A1
      receptors and thus play a role in protenction against anoxic injury. ATP
      sensitive potassium channels may not be involved in the mechanisms of adenosine
      action.

PMID- 10074223
TI  - [Relationship between reaction of membrane potential and size of glomus cells in
      rat carotid body during hypoxia].
AB  - The membrane potentials (Em) of 85 cultured isolated glomus cells were measured
      by intracellular recording. The shapes of glomus cells were recorded by
      microscopic photograph and the cell diameter was measured by micrometer enlarger.
      The glomus cells with different diameters exhibited two distinct responses to
      hypoxia. The glomus cells with diameter shorter than 10 microns were depolarized
      in response to hypoxia, while the cells with diameter over 10 microns were
      hyperpolarized during hypoxia. Thus, it is sugested that glomus cells may be
      divided into two functionally different subtypes. Although the smaller glomus
      cells depolarized more seriously under extreme hypoxia, the degree of hypoxia
      could not change the original response pattern of glomus cells to hypoxia.

PMID- 10074224
TI  - [Effects of hypoxia on the morphology and proliferation of cultured pulmonary
      arterial smooth muscle cell].
AB  - The effects of hypoxia (2.5% O2 and/or < 1% O2) on bovine pulmonary arterial
      smooth muscle cell (PASM) proliferation and phenotype change were investigated
      using immunocytochemical analysis and H- TdR incorporation. The results showed
      that hypoxia initiated the change of PASM from contractile phenotype to synthetic
      phenotype. The synthetic phenotype smooth muscle cell was characterized by
      increase in endoplasmic reticulum and mitochondria, and by decrease in alpha
      actin and muscle fiber at the end of 24 h hypoxia. Then the endoplasmic reticulum
      became dilated, the mitochondria became swollen and myelin figure appeared after
      48 h hypoxic exposure. PASM 3H-TdR incorporation was decreased at the end of 6 h
      hypoxia (P < 0.05), then increased gradually at the end of 12 h. PASM DNA
      synthesis was significantly stimulated by 24 h hypoxia (P < 0.05). Flow
      cytometric DNA analysis revealed that hypoxia induced significant enhancement of
      G2/M phase of PASMs, decreased G0/G1 phase of PASMs (P < 0.001), and only
      increased S phase of PASMs in 12 h anoxia group (P < 0.05), but decreased S phase
      of PASMs from 24 h to 48 h (P < 0.001). Immunocytochemical reaction of
      proliferating cell nuclear antigen (PCNA) in PASM under anoxic condition was more
      stronger than that of normoxic PASM at 24 h. These results suggest that hypoxia
      may at first inhibit and then stimulate PASM proliferation and induce phenotype
      change, which may lead to the development of hypoxic pulmonary hypertension.

PMID- 10074225
TI  - [Effects of acute hypoxia on variability of event-related potentials].

PMID- 10074226
TI  - [Effects of acute repeated hypoxia on levels of adenosine and its A1 receptor in
      mouse brain].
AB  - Experiments were conducted on Kunming mice. Content of adenosine (ADO) and its
      metabolites in the brain was measured by specific enzymatic method, and
      radioligand binding method was used to study ADO A1, receptor. ADO content of the
      hippocampus in group C (hypoxia exposure for four runs) was markedly higher than
      that in groups A (control, without hypoxia exposure) and B (hypoxia exposure for
      one run), showing that ADO content can be cumulatively increased in the
      hippocampus, which is more sensitive to ischemia and hypoxia, during acute
      repeated hypoxia exposures. A1 receptor density, but of group C was significantly
      lower than that of group A and no difference was seen between groups B and C, but
      A1 receptor affinity in the hippocampus, pons and medula oblongata in group C was
      significantly higher than that in group A, implying that during acute repeated
      hypoxia there may be some mechanisms preventing A1 receptor density from
      decreasing further and making A1 receptor affinity increase in some brain
      regions. These results indicate that cumulatively increased ADO in the
      hippocampus via A1 receptor may play a neuroprotective role in CNS as an
      inhibitory neuromodulator and thus contribute to the formation and development of
      acute hypoxia adaptation or tolerance.

PMID- 10074228
TI  - [Changes of distortion product otoacoustic emission in guinea pigs after acute
      anoxia].

PMID- 10074227
TI  - [Effects of exposure to hypoxia on the skin temperature and glycogen content of
      frostbitten feet in rabbits].
AB  - Effect of exposure to acute hypoxia and hypoxia for 2 weeks on the skin
      temperature and content of glycogen of frostbitten feet in rabbits were observed.
      The results showed that the skin temperatures and content of glycogen were
      decreased in frostbite at normoxia (FN) group frostbite during acute hypoxia
      (FAH) group and frostbite hypoxia for 2 weeks (FH-2w) group. After treatment with
      warm chlorhexidine immersion the skin temperature and glycogen content in treated
      feet of FN and FAH group were increased, as compared with untreated feet.
      However, there was no difference between treated and untreated feet in FH-2w
      group, suggesting that there may be severe disturbance of blood circulation on
      frostbitten feet under this condition.

PMID- 10074229
TI  - [Effects of different intensity endurance training on hypothalamus-pituitary
      regulatory function].
AB  - Effects of different intensity endurance training on several main hormones
      related to exercise in the rat hypothalamus-pituitary-adrenal axis-gonadal axis
      were studied. The results indicated that different intensity endurance training
      played different roles in their synthesis and release. In 36 m/min training
      group, the reserve of beta-endorphine beta-EP, in hypothalamus-pituitary, the
      capacity of body stress and aerobic capacity were increased, whereas the stress
      level in exercise, the luteinizing hormone LH content were decreased as compared
      with other groups. It is suggested that proper endurance training may elevate the
      sports capacity in which beta-EP may play an important role in regulating adrenal
      axis and gonadal axis directly and indirectly.

PMID- 10074230
TI  - [Changes of visual evoked potentials during elevation of brain temperature in
      rabbits].

PMID- 10074231
TI  - [Protective effect of ciliary neurotrophic factor against the ototoxicity of
      gentamicin in guinea pigs].
AB  - The effect of ciliary neurotrophic factor (CNTF) on gentamycin induced deafness
      was observed by Preyer's reflex, auditory brainstem evoked potential, bioelectric
      response of the cochlea and histomorphological examination of surface preparation
      of cochlea. It was found that CNTF was capable of reducing ototoxicity of
      gentamicin in guinea pigs, thus protecting hair cells of cochlea and auditory
      nerves.

PMID- 10074232
TI  - [Effects of increasing perilymph calcium levels on various cochlear potentials].
AB  - In the present study, we examined the effects of increasing perilymph calcium
      (12.20 mmol/L) on guinea pig cochlear functions. The results demonstrated that
      high calcium perilymphs suppressed the magnitude of compound action potential of
      auditory nerves (CAP) with a prolongation of N1-peak delay at a constant
      intensity (90 dB SPL), but not of cochlear microphonics (CM). High calcium
      perilymph didn't change general endocholear potential (G-EP), while reduced the
      rapid change of EP at on and off set of 115dB SPL white noise exposure.
      Furthermore the value of negative potential (N-EP) induced by anoxia was
      decreased because of high calcium perfusions. Machanisms of these effects were
      discussed.

PMID- 10074233
TI  - [Studies on cell senescence induced by D-galactose in cultured neurons and
      fibroblasts].
AB  - The cell senescence induced by D-galactose (D-gal) in cultured rat fetal brain
      neurons and human fetal lung fibroblast was investigated in vivo and in vitro.
      The results showed pronounced decreases in nerve cell diameters, number of
      process and percentage of multiprocess neurons including "pyramidal" and
      "stellate" shaped and a rather high level of mortality rate observed in D-gal
      treated (8 g/L) neurons. Lessening of the proliferating population of lung
      fibroblast taken from rat treated with D-gal (50 mg/kg.d, subcutanous injection
      for 6 weeks) was observed. We have also determined the changes of cell cycle in
      human fetal lung fibroblast cells treated with D-gal (8 g/L): the proportion of
      the G0-G1 cells increased but the G2-M and DNA level and the results showed that
      decreased and the cell growth rate declined in comparison with those of the
      control. Lipid peroxidation was observed in both kinds of cells because D-gal was
      proved to have action of decreasing SOD activity and increasing MDA content, the
      results found in D-gal-treated rats were similar to those observed in
      hypoxanthine-xanthine oxidation reaction system (O2-), indicating that reactive
      oxygen was generated in the course of D-gal metabolism. It is concluded that D
      gal has the hastening effect on cell senescence and oxidative stress might be
      responsible for this aging effect.

PMID- 10074234
TI  - [Preiliminary studies on the efficacy and mechanism of interleukin-3 in the
      treatment of myelosuppression in mice].
AB  - The effects of recombinant interleukin -3 (IL-3) on the myelosuppression induced
      by irradiation and cyclophosphamide (CY) were observed in mice. The experimental
      results were as follows: (1) Intraperitoneal (i.p.) or subcutaneous (s.c.)
      injections of rh IL-3 daily for 5 days immediately after irradiation could
      alleviate the radiation-induced hematopoietic injuries. The yields and the
      numbers of CFU-E, BFU-E, CFU-Mix and CFU-GM in femural marrow in mice on the 9th
      day post exposure to 7 Gy gamma-rays were much higher than those in control
      animals. Meanwhile, rh IL-3 showed a weak influence on the numbers of bone marrow
      nucleated cells (BMC) and endogeneous CFU-S. (2) Subcutaneous administration of
      rh IL-3 for 5 consecutive days brought a favour of CY treated mice to elevate the
      yields of hematopoietic progenitor cells. (3) The effects of rh IL-3 on
      myelosuppression induced by radiation or CY were closely related to the route of
      administration, administration schedules, dosage of this cytokine and the disease
      state as well. So it seemed important to research still further an appropriate,
      optimal and flexible guide for clinical use. (4) In vitro rh IL-3 had no effect
      on the growth of murine BMC and CFU-GM. In comparison with control, after
      coculture with rmIL-3 (recombinant mouse interleukin (3)) BMCs of normal mice and
      mice irradiated with 2 Gy gamma-rays proliferated more rapidly and the yield of
      CFU-GM in them were higher. (5) The mechanism of the effects of rh IL-3 in marrow
      hypoplastic mice might be related to the indirect promoting influences on the
      proliferation and/or differentiation of the radiation damaged hematopoietic
      progenitor cells and/or hematopoietic stem cells.

PMID- 10074235
TI  - [Protective effects of hepatic stimulator substance on experimental liver
      fibrosis in rats].

PMID- 10074236
TI  - [Effects of K+ channel openers on voltage-dependent K+ channel behavior in airway
      smooth muscle of guineapig].
AB  - In order to determine whether the K+ channel openers (PCOs), which are suggested
      to open K+ channels and to relax bronchial smooth muscle, would directly activate
      voltage-dependent K+ channels, single channel currents were studied on cell
      attached and inside-out patches of smooth muscle acutely dissociated from bronchi
      of guinea-pig. The resting membrane potentials measured in whole-cell recording
      configuration showed no difference with control when cromakalim and lemakalim
      were applied extracellularly, which, however increased the conductance values of
      K+ channels with depolarization from 75.2 +/- 5.1 pS to 85.9 +/- 11.8 pS and 82.1
      +/- 5.5 pS, respectively. The channels kinetics were also affected by PCOs. Mean
      open time (tau o) and open probability increased, in which the effects of
      lemakalim was stronger than that of cromakalim. Both PCOs elicited the
      multichannel activities in some patches. It is suggested that PCOs could evoke K+
      channels with depolarization and stimulate K+ efflux, which may affect the
      excitability of muscle cells.

PMID- 10074237
TI  - [Discordance of increase in stress proteins in right and left myocardium of
      perfused isolated rat heart].
AB  - Discordance of functional and structural changes in right and left myocardium has
      been considerably discovered in various physiologically stimulated hearts and
      patients with cardiopathy, but the reasons for that have not yet been known. In
      the present study, induction of stress proteins, i.e. heat shock proteins, was
      analyzed and compared between the left and right myocardium of normoxic and
      hypoxic perfused isolated rat hearts by the methods of two dimensional
      electrophoresis and silver staining. The results showed that three Hsp70 isoforms
      (molecular weight 68, 70 and 72 k mu) with pI ranging from 6.3 to 7.3 were
      increased distinctly in both right and left myocardium under the conditions of
      perfusion as mentioned above. Moreover, the amount of the stress proteins
      increased in the right myocardiums was higher than that in the left myocardium,
      indicating that the response of right heart to the stimulus of hypoxic or
      normoxic perfusions is different from the reaction of left heart, and the extent
      of protection in left and right heart by stress proteins is unlike. In addition,
      the activity of catalase was found to be obviously declined in all perfused
      isolated hearts. It was suggested that the different increase in stress proteins
      may be due to different structure and status of right and left ventricle and the
      oxidative stress may be one of the important reasons to induce or enhance the
      synthesis of stress proteins.

PMID- 10074238
TI  - [Effects of pituitrin on the time domain and power spectrum of high-frequency ECG
      in mice].

PMID- 10074239
TI  - [Studies on the mechanism of protection of cultured neurous by ketamine
      anoxia/reoxygenation-induced injury].
AB  - The effects of anoxia/reoxygenation (A/R) and glutamate on cultured cortical
      neurons from 16 to 18-day-old fetal rats and the protective effect of ketamine
      were studied. The 12-day cultures of 12 days were exposed to anoxia (5 h)
      followed by reoxygenation (0-24 h). Following progressive A/R, the release of
      lactate dehydrogenase (LDH) into the bathing medium obviously increased and
      exogenous glutamate (3 h) also markedly increased the release of LDH. When the
      cultures were pretreated with ketamine before A/R, the amounts of LDH efflux in
      culture medium were significantly less than those of controls. These results
      demonstrate that the cultured cortical neurons are seriously damaged by A/R and
      exogenous glutamate. Such damage could be attenuated by ketamine, suggesting that
      the neurotoxic effect of glutamate and NMDA (N-methyl-D-aspartate) receptors play
      an important role in the process of ischemia-induced damage in the brain.

PMID- 10074240
TI  - [Effects of lithium chloride and harringtonine on the differentiation,
      proliferation and c-myc proto-oncogene expression of HL-60 cells].
AB  - This research was to observe the effects of lithium chloride (LiCl) and
      Harringtonine (HT) on the proliferation and differentiation of HL-60 leukemia
      cells. The results obtained by liquid suspension culture, semi-solid colony
      culture and 3H-TdR incorporation into HL-60 cells indicated that different
      concentrations of LiCl (5-20 mmol/L) and HT (10(-8)-10(-5)mol/L) exerted the
      inhibitory effects in a dose-dependent manner on HL-60 cell proliferation
      respectively. When LiCl (10 mmol/L) and HT (10(-7) mol/L) were added together in
      the liquid culture or semi-solid culture of HL-60 cells, they showed much greater
      inhibitory effect than that by each agent separately. It was discovered that
      there was induction of the differentiation of HL-60 cells by lithium and HT and
      the induction of HL-60 cells differentiation by HT was markedly enhanced by the
      addition of low concentration of lithium. This work also showed that by treating
      HL-60 cells with lithium and HT, the expression of the c-myc proto-oncogene was
      markedly decreased as measured by RT/PCR-mRNA (P < 0.01). These findings provide
      some evidence of the mechanismcausing leukemic change and of the potential use of
      lithium and HT in the treatment of leukemia and in vitro purging of leukemic
      cells for autologous bone marrow transplantation.

PMID- 10074241
TI  - [Effect of ginsenosides on nucleolar organizer region of neuron and sprouting of
      mossy fibre terminals of hippocampus in rats].
AB  - During the production of long-term potentiation (LTP) of the granular cell layer
      in hippocampal dentate gyrus (DG) and the enhancement of the ability of the
      memory retention in rats induced by ginsenosides (GSS), the effects of GSS on the
      number of silver-nucleolar organizer region (Ag-NOR) of neuron and the sprouting
      of mossy fiber (MF) terminals in hippocampus were studied. Giving GSS for 7 days,
      the amplitude of population spike (PS) increased by 87.71 +/- 1.91% and the onset
      and peak latency of PS decreased by 16.60 +/- 1.53%, and 13.5 +/- 0.87%
      respectively. Meanwhile, GSS could markedly promote the ability of memory
      retention in rats. In CA3 and DG area, the average number of Ag-NOR of single
      pyramidal and granular cell in the three GSS groups increased by 66.17 +/- 2.32%
      and 72.07 +/- 0.93% respectively (P < 0.01). Moreover in CA3, the average of
      rating scales of MF terminals sprouting in three GSS groups increased 1-3 times
      as compared with saline groups (P < 0.01). It is suggested that GSS could enhance
      the transcriptional activity of rDNA and the synthetic ability of protein in
      hippocampal neuron, as well as promote the sprouting of MF terminals in
      hippocampus for increasing the efficiency of transmission by hippocampal
      synapses.

PMID- 10074242
TI  - [The inhibitory effect of steroids on ethanol induced gastric ulcers and the
      relation to GABA uptake].

PMID- 10074243
TI  - [The effects of endothelin and bFGF on proliferation of MC and synergetic effect
      of insulin].
AB  - The effects of basic fibroblast growth factor (bFGF), insulin and endothelin-1
      (ET-1) on proliferation of rat glomerular mesangial cells (MC) cultured in vitro
      and the synergetic effects of insulin and bFGF or ET-1 on MC proliferation were
      determined by H-TdR incorporation experiment. The results showed that bFGF at
      concentrations of 5-200 ng/ml and insulin at concentrations of 0.1-2.4 U/ml
      significantly increased the value of 3H-TdR incorporated into MC (the cpm value).
      The effect of ET-1 on the cpm value was different at different doses. At
      concentration ranging from 10(-9) mol/L to 10(-7) mol/L, the cpm value
      significantly increased with increasing the concentration of ET-1, and the
      highest value was at concentration of 10(-8) mol/L, However, the cpm value
      decreased at concentration of 10(-6) mol/L ET-1. When MCs were incubated
      simultaneously with insulin and bFGF or lower concentration of ET-1 (< 10(-8)
      mol/L), the cpm value was significantly higher than the sum of that induced
      independently by insulin and bFGF or ET-1. But the joint effect of insulin and
      higher concentration of ET-1 (> 10(-7) mol/L) on the cpm value was lower than the
      sum of that induced separately by insulin and ET-1. It was indicated that bFGF,
      insulin and ET-1 significantly stimulated MC proliferation; insulin exhibited
      positive synergetic effect with bFGF or lower concentration of ET-1 on MC
      proliferation, negative synergetic effect with higher concentration of ET-1 on MC
      proliferation.

PMID- 10074244
TI  - [Role of interleukin-8 in indomethacin-induced stomach ulcer in rats].

PMID- 10074245
TI  - [Role of endothelial-derived nitric oxide and its synthase in the development of
      hypoxic pulmonary hypertension in rat].
AB  - To clarify the role of endothelial-derived nitric oxide (EDNO) and its synthase
      (NOS) in the normal and hypertensive pulmonary vasculature, activity of
      endothelial NOS in the lungs, ENDO-dependent vasodilating response induced by
      bradykinin (BK), and cGMP content of lung tissue in normoxic and hypoxic rats
      were investigated. We also studied the effects of NOS inhibitor-L-NAME on the
      activity of NOS, cGMP content, mean pulmonary arterial pressure (mPAP) and
      carotid systolic arterial pressure (CAPs) in both rats. The results were as
      follows (1) In normoxic rats there was no NOS activity in the endothelium of
      small vessels (phi < or = 80 microns) and no relaxing response to BK. Long-term
      administration of L-NAME obviously inhibited the activity of ecNOS and cGMP
      content in the lungs of normoxic rats, therefore it led to the increment of CAPs
      but failed to elevate mPAP. (2) After hypoxic exposure for 10 days, NADPH
      diaphorase (NADPH-d and ecNOS immunoreactivity turned to be positive in the
      endothelium of small vessels with diameter less than 80 microns. BK-induced EDNO
      dependent vasodilation, the enzyme activity of cNOS and cGMP content in the lungs
      of hypoxic rats were significantly enhanced as compared with normoxic rats. Long
      term administration of L-NAME in hypoxic rats markedly inhibited the enhancement
      of cNOS enzyme activity, the production of EDNO and cGMP content in rat lungs,
      consequently it significantly decreased mPAP but elevated CAPs obviously. These
      results suggest that the role of EDNO in maintaining the low basal tone of normal
      adult pulmonary circulation remain to be studied more precisely. The increased
      activity of ecNOS and the enhancement of EDNO synthesis might act to moderate the
      hypertension. The excess synthesis of EDNO might be toxic to the endothelium of
      pulmonary vessels, therefore potentiating the development of pulmonary
      hypertension.

PMID- 10074246
TI  - [The effects of lidocaine on lymphocyte beta-adrenergic receptor at different
      pH].
AB  - The effects of lidocaine on beta-adrenergic receptor binding and the yield of
      epinephrine-stimulated cAMP at different pH were measured by radioligand binding
      assay and radioimmunoassay. The results showed that the binding of H-DHA to the
      receptor and yield of epinephrine-stimulated cAMP increased with increasing pH (P
      < 0.001) and lidocaine inhibitory potency also increased with increasing pH (P <
      0.001); The results indicate that the response to beta-agonists would increase
      with pH during cardiopulmonary resuscitation when lidocaine is not present, but
      it would not increase with pH when lidocaine is present, suggesting that
      lidocaine may inhibit binding of beta-agonists to receptor by changing lipid
      fluidity of cell membrane with increasing pH.

PMID- 10074247
TI  - [Effects of lymph on ventricular contractile function in rats during hemorrhagic
      shock].

PMID- 10074248
TI  - [Effects of endothelin-1 on the progesterone production of rat preovulatory
      ovarian granulosa cells].
AB  - The effect of endothelin-1 (ET) on progesterone production of isolated rat
      granulosa cells and its mechanism were investigated. ET could inhibit the hCG
      stimulated progesterone production significantly at the concentration of 10(-8)
      mol/L (P < 0.05, n = 6) and highly significantly at the concentration of 10(-7)
      mol/L (P < 0.05, n = 6), but ET did not inhibit the basal progesterone production
      at various concentrations (10(-10)-10(-7) mol/L). Further experiments showed that
      the inhibitory effect of ET on the hCG-stimulated progesterone production could
      be reversed by rabbit antiserum to ET (ET-A, 1:1000) or cAMP (10(5) mol/L). ET
      could decrease the binding sites and the affinity constant (ka) of LH/hCG
      receptor on granulosa cells. All these findings suggest that ET may be an
      intraovarian regulatory factor which may inhibit progesterone production
      stimulated by hCG from rat granulosa cells through inerfering LH/hCG receptor
      function and cAMP formation.

PMID- 10074249
TI  - [Effect of catecholaminergic agonists and antagonists on adaptive gastric mucosal
      protection in rats].
AB  - The gastric mucosal damage caused by 70% ethanol significantly decreased in rats
      pretreated with chronic mild restraint stress (CMRS, P < 0.001). This adaptive
      mucosal protection induced by CMRS was absent in sympathectomized rats, while the
      administration of isoprenaline or dopamine could partially, and norepinephrine
      could not, restore the protection. In rats with rntact sympathetic nerve,
      preinjection of haloperidol or propranolol inhibited CMRS-induced protection
      which, however, was not affected by phentolamine. No change in plasma
      somatostatin level was observed either in stress or sympathectomized rats alone
      or in stress plus sympathectomized rats. The results suggest that the sympathetic
      nerve or its mimetic agent ang this is are involved in the adaptive protection of
      the gastric mucosa possibly mediated through beta and dopamine receptors.

PMID- 10074250
TI  - [Protective effects of 15-methyl-prostaglandin F2 alpha on primary cultured rat
      hepatocyte against CCl4-induced injury].
AB  - The effect of 15-Mt-PGF2 alpha on CCl4-induced injury of primary cultured
      hepatocytes was studied. 15-Mt-PGF2 alpha treatment (2 mg/L) significantly
      decreased CCl4 (10 mmol/L)-induced damages of primary cultured rat heptocytes as
      indicated by decreases GPT and GOT leakage and LPO production. 15-Mt-PGF2 alpha
      significantly promoted 3H-uridine incorporation into RNA and [3H]-thymidine
      incorporation into DNA of the rat hepatocytes. Cytopathology study showed that 15
      Mt-PGF2 alpha attenuated damages of mitochondria, endoplasmic reticulum and
      ribosome caused by CCl4. 15-Mt-PGF2 alpha appeared to maintain the stability of
      rat hepatocytes by inhibiting lipid peroxidation. These results indicated that 15
      Mt-PGF2 alpha has notable protective effect on primary cultured rat hepatocytes
      against CCl4-induced damage by reducing lipid peroxidation and promoting
      synthesis of RNA and DNA.

PMID- 10074251
TI  - [Changes of nitric oxide and endothelin content in pulmonary hypertension during
      early stage of cecal ligation and puncture in rabbits].

PMID- 10074252
TI  - [Regulation of cardiovascular myogenic tone via G-protein-sensitive transmembrane
      signal pathways].
AB  - Effects of cellular hypoxia on [Ca2+]i in CK1.4 cells expressed Na(+)-Ca2+
      exchange protein were determined by fura-2 fluorescence imaging. In vitro
      perfused of canine cardiovascular samples (37 degrees C), changes of aortic,
      cervical, pulmonary arterial smooth myogenic tone and cardiac papillary myogenic
      tone were measured by mechanic-electrical transducers via a computer-aid
      autosampling system. In the whole dogs, pharmacolkinetic parameters of a VISA
      agent at three dosages were calculated by 125Isod-1 scintillation counting
      according to a 6 x 6 statistical model. The results indicated that 1. hypoxia
      inhibited the Na(+)-Ca2+ exchange protein induced by and elevated Ca(2+)-influx
      and [Ca2+]i in the CK1.4 cells; 2. hypoxic perfusions depressed the AlF4-(
      )activated myogenic vasoconstriction in aortic, cervical and pulmonary arteries,
      but facilitated the cardiac papillary myogenic contraction Ca(2+)-influx-induced,
      the finding was consistent with the first result; and 3. the VISA agent
      distributed in the cell together with AlF4- simulated and activated G-protein
      sensitive transmembrane sygnal, and signhificantly improved the oxidative
      injuries of the transmembrane macrowolecules and cardiovascular contraction
      proteins such as Na(+)-Ca2+ exchange protein induced by hypoxia.

PMID- 10074253
TI  - [Changes of gastrointestinal electric motility during experimental stress gastric
      ulcer in rats].

PMID- 10074254
TI  - [Brain dialysis--a new technique for determining the release of neurotransmitters
      and neuropeptides].
AB  - Brain dialysis, also called microdialysis, is a new technique based on the push
      pull cannula. It can be used for continuously perfusing and collecting perfusate
      of certain brain areas in freely moving animals. Coupled with high performance
      liquid chromatography (HPLC) and radioimmunoassay (RIA), brain dialysis is
      allowed to determine the extracellular changes of many neurotransmitters in the
      brain, such as acetylcholine, noradrenaline, dopamine, 5-HT and their
      metabolites, free amino acids, small peptides, phosphoethanolamine, vitamins,
      various ions and so on.

PMID- 10074255
TI  - [Culture and characterization of rat lung microvascular endothelial cells].
AB  - Cultures of rat lung microvascular endothelial cells (RLMECs) were obtained from
      perepheral lung tissue. The lung tissue was cut into small pieces and cultured
      with RPMI-1640 containing 20% bovine calf serum, 90 micrograms/ml heparin, 4
      mmol/L L-glutamine, 100 mu/ml penicillin and 100 micrograms/ml streptomycin.
      Erythrocytes and leukocytes left the tissue first, followed by RLMECs.
      Fibroblasts and other cells grew after 72 hours of culture. After 60 hours of
      culture, the lung tissue was discarded. RLMECs in flask showed regular
      cobblestone morphology and positive for binding of the lectin Bandeiraea
      simplicifolia I and indirect immunofluoresence staining with factor VIII
      antiserum.

PMID- 10074256
TI  - [Primary culture of fetal rat gastric mucosal epithelium].
AB  - A method for primary cell culture of fetal rat gastric fundic epithelial cells
      was developed. The tissue was incubated with 0.125% trypsin at 4 degrees C for 8
      10 hours. The epithelial cells isolated were then cultured in DMEM/F12 medium
      supplemented with 20% fetal calf serum. Within 24 hours the cells attached to the
      culture plate and became confluent in 3 days. On phase contrast microscopy, over
      90% of cell possessed epithelial characteristics. Immunocytochemical studies
      showed: (a) 90% of cells were positive in anti-cytokeratin antibody staining; (b)
      90% of the epithelial cells contained PAS positive granules; (c) 20% of
      epithelial cells gave a strong reaction for succinic dehydrogenase activity.
      Electron microscopy (EM) showed microvilli on the surface of cells, junctional
      complexes (tight juntion and desmosome), glycogen and mitochondria.
      Autoradiographic studies showed that these cells possessed the capability to
      synthesize DNA and this ability was maximum on day 2. This in vitro system may
      provide a valuable model for studies of cellular functions of gastric mucosa.

PMID- 10074257
TI  - [Study on adaptive changes of myocardial ultrastructure after endurance training
      at different intensities in rats].
AB  - The purpose of the investigation was to determine the adaptive changes of central
      mechanism of aerobic metabolism and to probe the best training intensity for
      developing the structure and function of heart most effectively. After endurance
      training at different intensities (including 26 m/min, 30 m/min, 36 m/min, 42
      m/min) for 16 weeks, the rats were decapitated. Left ventricle were excised soon
      and were then processed for electron microscopy. Morphometry was performed at
      image analysis system. Quantitative analysis of ultrastructure of left ventricle
      and capillaries indicated that the best development of mitochondria inner
      membrane and cristea, the maximum improvement in number of capillaries, the most
      obvious enlarging of capillary cavity and the most remarkable shortening of
      maximum oxygen diffusion distance from capillary wall to the mitochondria
      appeared after training at the highest speed (42 m/min). It is demonstrated that
      after endurance training at different intensities the ultrastructure of all
      training groups showed good developments in varying degrees. Furthermore,
      endurance training at suitably high intensity could improve adaptation of
      myocardium most effectively.

PMID- 10074258
TI  - [The effect of exercise on the androgen receptor binding capacity and the level
      of testosterone in the skeletal muscle].
AB  - Androgen receptor (AR) binding and testosterone (T) level of skeletal muscle of
      rat at the different conditions were observed in this study. The exhausted
      exercise could up-regulate the AR binding of levator ani muscle, but decrease the
      T level in quadriceps. The long term exhausted exercise had no effect on the AR
      binding of quadriceps. The fitness exercise could up-regulate the AR binding of
      quadriceps but have no significant effect on the T level in quadriceps. There was
      no effect on the AR binding but T level was increased after injection of HCG for
      4 days in quadriceps. The increase of T level in skeletal muscle after injection
      of HCG for 4 days was higher than that for 8 days. From these results it is
      suggested that the effect of exercise on the regulation of hormone on skeletal
      muscle may be in two directions. Both AR binding capacity and T level must be
      considered in skeletal muscle anabolism.

PMID- 10074259
TI  - [Effect of different training time and loads on the metabolism of carbohydrate,
      fat and protein].
AB  - Twenty-five athletes were selected to receive three kinds of loads (endurance,
      strength and sprint training) at the same training time, as well as to receive
      the same kind of load at different time (morning, am. pm), then the tricarboxylic
      acid (TCA) cycle products, free fatty acids (FFA), urea nitrogen, creatinine and
      free amino acids contents in their serum were measured. The results showed that
      at the same training time, different loads led to different physiological
      effects, while the same kind of exercise training resulted in more protein
      catabolism in p.m. than in the morning or a.m. Endurance or training in the
      morning had considerable influence on the levels of TCA cycle products and FFA
      components. Training in p. m. may be favourable to improving the quality of the
      sports of speed and strength.

PMID- 10074260
TI  - [Role of Na+/Ca2+ exchange blocker in rat hippocampal injury during anoxia].
AB  - Effects of Na+/Ca2+ exchange blocker, Benzamil, on rat hippocampal slices and on
      cultured hippocampal neuronal [Ca2+]i (intracellular free Ca2+ concentration)
      during anoxia were investigated by means of microelectrode recording technique
      and laser scanning confocal microscope respectively. The results showed that the
      PV sustained time of hippocampal slices pretreated with Benzamil (50 mumol) after
      anoxia was markedly longer than that of control, suggesting that inhibition of
      Na+/Ca2+ exchange can delay the irreversible injury to hippocampal cells.
      Moreover, by using a confocal microscope we found that acute anoxia induced a
      rapid increase of [Ca2+]i in hippocampal neurons and this could be significantly
      attenuated by 20 mumol Benzamil. All these results indicate that Na+/Ca2+
      exchanger is involved in the anoxic injury to rat hippocampus and it may be one
      of the major ways leading to the anoxia-induced [Ca2+]i increase of hippocampal
      neurons.

PMID- 10074261
TI  - [Mutual regulation of proliferation between pulmonary artery endothelial cells
      and pulmonary smooth muscle cells in vitro].
AB  - Vascular endothelial cell are closely related to vascular smooth muscle cells in
      structure and function. The interactions between them may play important roles in
      the modulation of function and structure of vascular wall. In the present study,
      the mitogenic regulations between cultured new bovine pulmonary arterial
      endothelial cell (PAEC) and pulmonary arterial smooth muscle (PASM) were
      investigated. When PAECs and PASMs were mixcultured, 3H-TdR incorporation into
      the mixed cells decreased significantly (P < 0.001 vs control). When PAECs and
      PASMs were cultured in conditioned medium from PASMs and PAECs respectively or
      they were cocultured, the proliferation of PAECs was inhibited while that of PASM
      was stimulated significantly (P < 0.05 vs control). It was also found that the
      concentration of cAMP increased but cGMP decreased in cocultured PASMs (P < 0.01
      vs control), while the concentration of both cAMP and cGMP decreased
      significantly in cocultured PAECs (P < 0.01 vs control). These findings suggest
      that PAECs and PASMs may regulate their proliferation each other through the
      second messenger system.

PMID- 10074262
TI  - [Uses of ramp voltage stimulus in whole cell recording].

PMID- 10074263
TI  - [Protein kinase C involved in the protecttve effect of anoxic preconditioning on
      vascular smooth muscle cells].
AB  - It has been known that anoxic preconditioning (APC) has protective effects not
      only on cardiomyocyte, but also on vasculature. However, the effects of APC on
      vascular smooth muscle cells (VSMC) is unknown. On the model of
      anoxia/reoxygenation (A/R) injury of rabbit VSMC, the effect of APC was observed.
      It was found that APC could increase the survival rate of VSMC after A/R injury,
      lower the leakage of lactate dehydrogenase (LDH) and protein from cells, and
      attenuate peroxidation injury and calcium overload of VSMC. The results also
      showed that PMA, an activator of protein kinase C (PKC), could mimic, but H7 or
      polymyxin B (inhibitors of PKC) could abolish the above protective effect of APC.
      It is suggested that the protective effect of APC on VSMC during A/R injury might
      be due to the activation of PKC.

PMID- 10074264
TI  - [Effects of hypoxia on the release of PDGF-B chain from pulmonary artery
      endothelial cells and on growth of pulmonary artery smooth muscle cells].
AB  - Platelet-derived growth factor (PDGF), content in hypoxic endothelial cells
      conditioned medium (HECCM) and normoxic endothelial cells conditioned medium
      (NECM) was determined using protein dot blot assay. The effects of HECCM and
      NECCM on the growth of pulmonary artery smooth muscle cells (PASMC) were assessed
      with [3H]-thymidine incorporation technique and flow cytometric analysis. PDGF
      content in HECCM was higher than that in NECCM. HECCM dramatically enhanced the
      DNA synthesis in PASMC and significantly promoted the cell cycle progression of
      PASMC from G0/G1 phase to S phase. In addition, administration of anti-PDGF-B
      chain monoclonal antibodies blocked markedly the DNA synthesis of PASMC
      stimulated by HECCM and obviously inhibited the entry of the cells from G0/G1
      phase to S phase. These results suggest that increased PDGF release from
      pulmonary artery endothelial cells under hypoxia could stimulate the
      proliferation of PASMC which may induce pulmonary vascular reconstruction and
      involve in the development of hypoxic pulmonary hypertension.

PMID- 10074265
TI  - [Expression of proto-oncogene fos in myocardial stunning].

PMID- 10074266
TI  - [Effect of hypoxia on spleen mono nuclear cell DNA content and proliferation of
      neonatal rats].
AB  - Effects of hypoxia on the immune function of neonatal rats at the age of 14 days
      as well as on the levels of ACh, catecholamine in spleen were studied. After the
      animals were exposed to hypoxia at 5 km simulated altitude in hypobaric chamber
      for 5 days, there was 43.4% decrease in DNA content in spleen mono nuclear cell
      and a 13.2% decrease in mono nuclear cell proliferation. Similar suppression of
      these two parameters of immune function in exposure to 7 km for 24 h was also
      noted, which decreased by 39% and 19.8% respectively. The suppressive effect of 7
      km for 24 h hypoxia on DNA content was partly blocked when rats were pretreated
      with DSP-4 intracerebroventricularly one day before hypoxia. The levels of
      catecholamine in spleen increased, while the levels of ACh decreased after 7 km
      exposure for 24 h. These observations indicate that hypoxia may suppress cellular
      function of neonatal rats and its action may be mediated by activation of
      sympathetic nervous system and inhibition of parasymphathetic one.

PMID- 10074267
TI  - [Effects of altitude training on pulmonary ventilatory function of race walkers].

PMID- 10074268
TI  - [The expression of hsp70 and BCL-2 genes in hippocampus of the rats exposed to
      cerebral ischemia and reperfusion].
AB  - In order to study the molecular mechanism of the selective vulnerability in
      central nervous system, the expression and distribution of hsp70 and BCL-2 gene
      were detected by using Northern blot analysis, in situ hybridization and
      histochemistry method in transient forebrain ischemia and reperfusion rats. It
      was found that hsp70 gene expression occurred and the synthesis of BCL-2 protein
      was inhibited in hippocampalCA1 region vulnerable to ischemia, while BCL-2
      protein was stained strongly and the signals of hsp70 were not observed in CA3
      region resistant to ischemia. The results indicate that the expression of hsp70
      gene may be not only as a marker for neuron ischemia, but also play a protective
      role in the neuronal injury. BCL-2, meanwhile, may have neuro-protective effect
      on the ischemic neurons.

PMID- 10074269
TI  - [Protection of hepatocyte growth factor against carbon tetrachloride injury in
      primary rat hepatocyte culture].
AB  - The protective effect of recombinant human hepatocyte growth factor (r-hHGF)
      against carbon tetrachloride (CCl4) injury in cultured rat hepatocytes was
      investigated. It was found that r-hHGF had cytoprotective effect on hepatocytes
      anainst CCl4 poisoning. Pretreatment with r-hHGF significantly increased the
      viability of cultured hepatocytes, reduced the leakage of intracellular alanine
      transaminase and potassium into the culture medium, as compared with the CCl4
      group. The results suggest that r-hHGF may protect hepatocytes against CCl4
      injury through lessening the severity of membrane lesion, preventing
      intracellular alanine transaminase and potassium leakage and sustaining the
      integrity of hepatocyte membrane.

PMID- 10074270
TI  - [Effects of different components of serum from radiation, burn and combined
      radiation-burn injury on L-type calcium channel of cultured myocardial cells].
AB  - The effects of different components of serum from radiation, burn and combined
      radiation-burn injury on the activity of L-type calcium channel in cultured
      myocardial cells were investigated in this study. The results revealed that the
      serum from different injury groups could all activate the L-type calcium channel
      of cultured myocardial cells. These changes altered the calcium level in cells,
      which might be an important cause of dysfunction in cardiovascular system. Among
      the components of postinjury serum, the effect of high molecular components (> 8
      10 kD) was not significant, whereas low molecule (< 8-10kD) and lipid components
      were the major effective components. The low molecule of postinjury serum
      affected not only on the opening activity of L-type channel, but also on the
      state of molecular movement in the membrane. The effect of serum lipids from
      injury groups could be depressed by SOD, which suggests that there may be free
      radical reactions during the serum lipids effect on calcium channel. The effects
      of serum and its components from combined radiation-burn group were the most
      intensive, and those from radiation injury were the weakest. The nature of the
      toxic material in serum remains to be further investigated.

PMID- 10074271
TI  - [Effects of oxygen free radical on the pacemaker current if in sheep ventricular
      Purkinje fibers].

PMID- 10074272
TI  - [The adaptive changes in vascular endothelial cell and resistance to frostbite in
      cold acclimated rats].
AB  - Several functions of vascular endothelial cells (VEC) were investigated in rats
      acclimated to cold (CA) and with frostbitten feet. The results indicated that in
      CA rats, the number of endothelial cells in circulatory blood and the contents of
      6-keto -PGF1 alpha and TXB2 in plasma were markedly higher, the activity of serum
      angiotensin I converting enzyme (ACE) was lower, compared with those in rats non
      acclimated to cold (NCA), whereas T/P ratio of the two groups was close to each
      other. After the rats were frostbitten, those parameters in NCA group increased
      sharply except for a decrease in ACE activity. But in CA group, those parameters
      decreased temporarily or did not change obviously and the tissue survival area
      (TSA) significantly increased. The above findings suggest that the adaptive
      changes in increase of metabolic turnover rate and function of VEC after cold
      acclimation may be beneficial to the body to enhance the resistance to frostbite
      and repairing ability.

PMID- 10074273
TI  - [Effects of EDRF on the vasoconstrictor action of phenylephrine in rat aorta].
AB  - The influence of endothelium-derived relaxing factor (EDRF) on the
      vasoconstrictor effect of phenylephrine on rings of rat aorta was studied in this
      paper. Rings of rat aorta, with or without endothelium, were suspended in organ
      chambers for the measurement of contractive force and contractive speed. All
      experiments were performed in the presence of indomethacin (10 mumol/L) to
      prevent the production of vasoactive prostanoids. When the preparations with
      intact endothelium were treated with methylene blue (10 mumol/L), an inhibitor of
      the target enzyme of EDRF, or NG-nitro-L-arginine (30 mumol/L), an inhibitor of
      EDRF formation, dose-contractive force curves of phenylephrine shifted to left:
      the EC30 value decreased 5-fold and the maximal response ratios were 1.6 +/- 0.4
      and 1.6 +/- 0.5 (n = 8) respectively. These results were similar to those
      observed after mechanical removal of the endothelium: a 3-fold decrease in the
      EC30 value and the maximal response ratio was 1.0 +/- 0.2 (n = 8), The latter
      results may be related to a little EDRF produced by vascular smooth muscle. Our
      results suggest that the vasoconstrictive effect induced by phenylephrine may
      also be regulated by EDRF production from vascular endothelium and smooth muscle.

PMID- 10074274
TI  - [Respiratory effects of microinjection of 2 types of amino acid neurotransmitters
      in medial areas of nucleus retrofacialis].

PMID- 10074275
TI  - [Influence of locus coeruleus stimulation on the vagal-cardiovascular reflex].
AB  - Experiments were performed on 36 anesthetized rabbits. By cervical vagal afferent
      stimulation (VAS) with lower electric frequency (5-8 Hz) and higher electric
      frequency (50-100 Hz), the depressor and pressor responses were established. Both
      of these responses accompanied by decreasing in renal sympathetic activity (RSA).
      With the parameters of vagal-pressure reflex and vagal-sympathetic stimulation
      reflex, effects of stimulation of the locus coeruleus on these were investigated.
      The vagal-pressure and sympathetic reflexes were significantly inhibited by
      electric and chemical (glutamate) stimulation of the locus coeruleus. Meanwhile
      both the electric and chemical stimulation of the locus coeruleus per se elicited
      the elevation of BP and RSA. These results together with the recently
      hypothesized global function of the locus coeruleus were discussed.

PMID- 10074276
TI  - [The ampullar endolymhatic potential in the guinea pigs].
AB  - The purpose of this paper is to understand the physiologic feature of the
      ampullar endolymphatic potential (AEP) in the guinea pigs (n = 35). The high
      input impedence microelectrode amplifier was used. The effects of asphyxia,
      furosemide and ischemia on the AEP were observed. The AEP was 4.55 +/- 1.35 mV,
      (n = 35) in normal. The potential decreased to 2.8 +/- 0.8 mV from the original
      level in two minutes of asphyxia. When the respirator was turned on the AEP
      started to rise abruptly after a latency. In all instances there was an overshoot
      above the preasphyxia level. When furosemide was administered i.v. at 100 mg/kg,
      no effects were seen in the AEP. After obstruction of the ascending aorta to
      cause ischemia, the AEP continued to decline until it reached a minimum of -19.4
      +/- 1.7 mV in 52.5 +/- 9.6 minutes and slowly returned to zero line in about 150
      minutes. There was no obovious effect after furosemide injection. The results
      suggest that AEP may deffer from as the positive potential in cochlea. It is
      produced in the specialized cells (dark cells) of the ampullar and has special
      electro-physiologic characteristics.

PMID- 10074277
TI  - [Effect of vagi excitation on HRV and the exploration of its mechanism].
AB  - The experiments were performed on rabbits anaesthetized with urethane and
      chloralose. The ECG heart rate and blood pressure were recorded. The power
      spectrum analysis of R-R interval (RRI) was done by computer. Electrical
      stimulation of nucleus ambiguus (NA), depressor nerve (DN) and the peripheral end
      of right vagus (RV) all evoked a decrease in heart rate and blood pressure (P <
      0.001), and an increase in LF, HF, LF/HF, TV and VLF (P < 0.05-0.001); The LF,
      HF, LF/HF, TV and VLF were significantly decreased (P < 0.05-0.01) by
      pretreatment with intravenous injection of atropine. The enhancement of LF during
      stimulating DN and NA were attenuated (P < 0.05) by prior intravenous injection
      of propranolol. It is suggested that vagus activity is one of the major regulator
      of HRV and mediates VLF. The HF is mediated only by vagi, while the LF is
      mediated by both vagi and sympathetic system.

PMID- 10074278
TI  - [The role of periaqueductal gray neurotensin in electroacupuncture analgesia].
AB  - The effect of periaqueductal gray (PAG) injection of neurotensin (NT), anti-NT
      serum (ANTS), and naloxone (Nx) on both the pain threshold and electroacupuncture
      (EA) analgesia in rat was investigated in this study. The potassium iontophoresis
      induced tail-flick was used to measure the pain threshold. NT administration
      induced an increase in pain threshold and enhanced EA analgesia. Injection of
      ANTS reduced the pain threshold significantly and diminished the effect of EA
      analgesia. Furthermore, pre-injection of Nx into PAG could weaken analgesia
      effect of NT and NT-EA analgesia. These results indicate that NT in PAG is
      involved in pain modulation and plays a role in EA analgesia. The effect of NT
      may be partly conducted by endogenous opiate peptides.

PMID- 10074279
TI  - [Mechanism of the antinociceptive role of opioids in nucleus cuneiformis].

PMID- 10074281
TI  - [Changes in the contraction and relaxation of abdominal aorta after thrombosis in
      rats].

PMID- 10074280
TI  - [Effects of acetyl-DL-leucine on the recovery of the locomotor equilibrium and
      spontaneous discharge of lateral vestibular nucleus neurons in unilateral
      vestibular neurectomized cats].
AB  - The effects of acetyl-DL-leucine (AL) treatment (28 mg/kg.day, p.o.) on the
      vestibular compensation were studied over period of 6 weeks in unilateral
      vestibular neurectomized cats. This investigation was performed by measuring the
      recovery time of locomotor equilibrium in the rotating beam test and recording
      the unitary extracellular activity of single neurons of lateral vestibular
      nucleus (LVN) in totally awake cats. The results showed that AL treatment
      strongly accelerated the recovery of locomotor equilibrium and significantly
      inhibited the recovery of resting spontaneous firing rate within the deafferented
      LVN neurons (n = 506) but improved the sensitivity and recovery of relative
      amount and proportion of neurons (n = 454) in response to head roll tilts in
      frontal plane. The neurophysiological mechanisms of AL role in the vestibular
      compensation were discussed.

PMID- 10074283
TI  - [Effects of lithium on the proliferation of murine high proliferative potential
      colony-forming cells and granulocyte macrophage colony forming unit in vitro].
AB  - The effects of LiCl on the proliferation of high proliferative potential colony
      forming cells (HPP-CFC) and granulocyte macrophage colony-forming unit (CFU-GM)
      from bone marrow of BALB/c mice were observed. The colonies of HPP-CFC were
      supported by IL-1, IL-6, WEHI-3 conditioned medium (WEHI-3 CM, which contained IL
      3) and L929 conditioned medium (L929-CM, which contained M-CSF); the colonies of
      CFU-GM were supported by WEHI-3 CM. It was shown that LiCl at concentrations
      ranging from 0.4 mmol/L to 2 mmol/L significantly inhibited the proliferation of
      HPP-CFC (P < 0.01), but concentrations ranging from 0.4 mmol/L to 1 mmol/L
      significantly increased the production of CFU-GM (P < 0.05), both effects
      displayed in dose-dependent manners. The different effects of LiCl on the
      proliferation of HPP-CFC and CFU-GM suggest that LiCl may induce HPP-CFC
      differentiation into more mature cells.

PMID- 10074282
TI  - [The effect of NO-like relaxing factor on vascular reactivity in tourniquet shock
      rat].
AB  - This work was done on rat tourniquet shock (ToS) model. It was found that
      reactivity of isolated perfused aortic ring to noradrenaline decreased, while
      cGMP content of the aortic tissue increased. These changes could be potentiated
      by perfusion with L-arginine (NO-precursor). On the other side, when the aortic
      ring was perfused with L-NNA (NO-synthesis inhibitor) or methylene blue (soluble
      cGMPase inhibitor), the changes could be attenuated. The effect of these drugs
      are independent of the presence of vascular endothelium. The results suggest that
      non-endothelium-derived NO-like relaxing factor may be one of the factors causing
      low vascular reactivity of the ToS animals.

PMID- 10074284
TI  - [Comparison between the effects of rhCNTF on sensory and motor neuron of chicken
      embryo].
AB  - The effects of rhCNTF on dorsal root ganglia (DRG) sensory neurons and spinal
      cord (SC) motor neurons of 10-day chicken embryos were observed with serum-free
      culture. The results indicated that rhCNTF supported the survival and
      differentiation of these neurons and showed certain dose-dependent manners. No
      effect was found at 0.5 ng/ml rhCNTF concentration, a little survival promotive
      effect at 1.0-1.5 ng/ml, peak effect at 4 ng/ml and no more effects from 8.0 to
      100 ng/ml. The survival number of neurons on 7th day was compared, and results
      showed higher sensitivity of sensory neuron to CNTF shortage than that of
      motoneuron. This suggests that survival effect of CNTF on motoneuron is only
      small part of its neurotrophic effects.

PMID- 10074285
TI  - [Gene expression of Is-1 gene in adult motor neurons].

PMID- 10074286
TI  - [Comparison of plasma thyroxin and insulin concentrations between 10-day old
      layer and broiler chickens].
AB  - In this study both sexes of 10 day old layer and broiler chickens were used to
      investigate plasma circulating concentrations of 3,3'-5-triiodothyronine (T3),
      thyroxine (T4) and insulin by using the radioimmunoassay (RIA) methods. The
      results were as follows: serum T3 concentration was higher in broilers than that
      in layers (P < 0.01), especially a significant difference between male strains
      was seen in this experiment (P < 0.001), and the levels of plasma insulin was
      significantly higher in male broilers than that in male layers (P < 0.001),
      however, no clear differences in plasma T4 was seen between strains and sexes (P
      > 0.05). In addition, there were sex differences in T3 and insulin levels in
      layers, that is to say, those in the female layers was higher than those in the
      male layers, but no clear deifference was seen between sexes in broilers. A
      significant positive correlation between T3, insulin and their weight gained (P <
      0.05). The results suggest that the levels of serum T3 and Insulin may influence
      the various growth rate during early posthatch development in layers and
      broilers.

PMID- 10074287
TI  - [Effect of acute cold exposure on plasma endothelin in rabbits with myocardial
      ischemia].

PMID- 10074288
TI  - [A simple nitric oxide exposure system for small animals].
AB  - A nitric oxide exposing system was designed for experimental research, which
      consist of equipments such as plexiglass chamber, blower, flowmeter, NO/N2
      cylinder, pure O2 cylinder, NOx analyzer, and O2/CO2 monitor. The efficacy of the
      whole system has been verified through our practice as shown by the following
      results: measured NO inside the chamber were close to designed NO concentration,
      measured O2 concentrations in the chamber were similar to that of the atmosphere,
      and the highest nitrogen dioxide (NO2) and carbon dioxide (CO2) concentrations
      were lower than 3 ppm and 0.3% respectively. The experimental facility is simple
      in construction, easy to be operated and convenient for research on effects and
      toxicity of long-term inhaled nitric oxide in small animals.

PMID- 10074289
TI  - [A continuous and constant rate administration method--mini-osmotic pump].
AB  - Mini-osmotic pump is a delicate administration method. When it is activated by
      water, mini-osmotic pump can deliver a variety of solutions or suspensions at a
      constant rate for days even up to several weeks. Since it is drived by osmotic
      pressure, the pumping rate is independent on the physical and chemical feature of
      the drugs. The pump from inside to outside consists of a cylindrical reservior,
      osmotic driving agent and semipermeable membrane.

PMID- 10074290
TI  - [Pulmonary injury in animals induced by compression-rapid decompression].

PMID- 10074291
TI  - [Extraction of P3 wave from ERP by using the wavelet transform].
AB  - A new time-frequency filter based on correlation of wavelet transform coefficient
      between mean ERP and single ERP is presented in this paper. This filter can
      extract the P3 wave from the background of eye-moving and spontaneous EEG
      activity.

PMID- 10074292
TI  - [Changes of tumor necrosis factor and free radical in aged rats with multiple
      organ failure].

PMID- 10074293
TI  - [Effects of rotational behavior in Parkinson disease with high frequency
      stimulation to subthalamic nucleus in rats].

PMID- 10074294
TI  - [The present situation of physiology in cellular-molecular trends].

PMID- 10074295
TI  - [The study of ICAM-1 expression after brain ischemia-reperfusion injury in rats].
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression was studied with rat
      transient cerebral ischemic model. The results showed that the expression of ICAM
      1 markedly increased after 1 h ischemia following 6 h reperfusion. Laser confocal
      microscope demonstrated that the FITC quantum on blood vessels after reperfusion
      was more than 47% compared to that of pure ischemia. MPO activity and light
      microscope observation showed that leukocytes accumulated in injured tissue 9 h
      after reperfusion. The local IL-1 content in brain tissue changed with different
      period of reperfusion time. Our data indicated that after brain ischemia
      reperfusion injury ICAM-1 expression was in time-dependent increase, the local IL
      1 secretion might up regulate the ICAM-1 expression, there were large amount of
      leukocytes accumulated in surrounding tissue, the increase of ICAM-1 expression
      was the prerequisite for leukocyte adhesion and migration.

PMID- 10074297
TI  - [Comparison of changes of bone mass, parathyroid hormone and calcitonin between
      two animal models of bone loss].
AB  - The changes in bone mass, blood parathyroid hormone (PTH) and calcitonin (CT)
      between rats suspended for 14 and 21 days, simulated weightlessness, and rats
      ovariectomized (OVX) for 30 and 60 days were observed. The results revealed that
      mineral density of T6 and L3 was significantly increased in rats suspended for 14
      days. T6 mineral density was also significantly increased in rats suspended for
      21 days, but L3 mineral density was significantly decreased. T6 mineral density
      had no change in OVX rats, but L3 mineral density was significantly decreased in
      them both for 30 and 60 days. Mineral content at proximal 1/3 of femur shaft was
      significantly decreased in rats suspended for 14 and 21 days, and in rats OVX for
      60 days. Bone biomechanical properties of suspended rats were more seriously
      deteriorated than that in OVX rats. There was no change in blood PTH, but CT was
      significantly increased in rats suspended for 14 and 21 days. Blood PTH and CT
      were significantly decreased in rats OVX for 30 and 60 days. The results indicate
      that the mineral redistribution and bone loss are presented in trabecular bone of
      suspended rats, but not in OVX rats. The deterioration of bone quality was more
      seriously in suspended rats than that in OVX rats. Both the cortical and
      trabecular bone in the two models were affected.

PMID- 10074298
TI  - [Study on the contents and the activities of antithrombin III in plasma of rats
      after frostbite].
AB  - The changes of the contents and activities of antithrombin III (AT-III) in plasma
      of rats following frostbite of both hind feet were investigated by means of
      rocket immunoelectrophoresis and single immunodiffusion. The results showed that
      the contents and the activities of AT-III were decreased in plasma of rats after
      frostbite and these changes were closely related to the degrees of cold injury.
      It is suggested that as a result of depressed anticoagulability, the blood
      coagulability could be increased after freezing, leading to the dysfunction of
      circulation and necrosis of local frostbitten tissue ultimately.

PMID- 10074300
TI  - [Effect of frostbite under hypoxia on microcirculatory perfusion in rats].
AB  - Changes of microcirculatory perfusion in rats following cold injury of right hind
      leg under hypoxia were investigated. Male Wistar rats weighing 200 +/- 20 g were
      randomly divided into three groups: frostbite at normoxia (FN) group; frostbite
      during acute hypoxia (4 h at 6000 m simulated altitude, FAH) group and frostbite
      during hypoxia after acclimation (exposure to hypoxia at 6000 m, 4 h daily for 4
      weeks, FHAC) group. The results showed that the microcirculatory perfusion of
      both hind legs decreased markedly in FN after cold injury. It suggests that the
      frostbite damage can affect microcirculatory perfusion of another leg besides the
      region of frostbite. The fall of microcirculatory perfusion before freezing in
      FAH group indicated that there was a compensatory blood redistribution during
      acute hypoxia. The changes of microcirculatory perfusion in FAH group post
      freezing indicated that acute hypoxia can aggravate the frostbite damage. The
      microcirculatory perfusion of FHAC group pre-freezing was significantly lower
      than that of FN and FAH group, and after freezing the perfusion of frostbitten
      leg in FHAC group was significantly lower than that in FN group, suggesting that
      hypoxia acclimation may cause disturbance of microcirculation and worsen the
      frostbite damage at high altitude.

PMID- 10074301
TI  - [The effect of endurance training and exhaustive exercise on metallothionein in
      rats].
AB  - To understand physiological role of metallothionein (MT) during exercise, MT
      levels in liver, brain, heart, lung, blood vessel, skeletal muscle and serum were
      observed in rats. The results showed that the levels of MT were decreased by 13
      34% in lung, liver, heart and skeletal muscle of rats trained by swimming for 10
      weeks and were increased by 21%-75% in skeletal muscle, heart, brain, lung and
      liver of rats after exhaustive swimming respectively, compared with normal
      control rats. (P < 0.05 and P < 0.01). But the levels of MT in blood vessel and
      serum were not changed in two groups of rats by swimming for 10 weeks and acute
      exhaustive swimming (P > 0.05). It is suggested that the different changes of MT
      levels under physical training and acute exhaustive exercise may be of importance
      in protection against oxygen free radicals.

PMID- 10074302
TI  - [Effects of aerobic exercise on regulation of activities of hepatic low density
      lipoprotein receptor in hypercholesterolemic rats].
AB  - The present study is to determine the effects of exercise on the regulatory role
      in activities of hepatic low density lipoprotein receptor (LDL-R) in experimental
      hypercholesterolemic (HC) rats. Using a specific assay for the binding of 125I
      LDL receptor to homogenate, the activity of hepatic LDL-R were measured. It was
      observed that the activity of LDL-R in HC decreased by 37% as compared with the
      normal control (NC) rats. HC rats also had a higher levels of serum total
      cholesterol (TC), LDL-Cholesterol (LDL-C) and apolipoprotein B (Apo B). The rats
      fed on high-cholesterol diet combined with exercise for 12 weeks (HE) had lower
      TC, LDL-C and Apo B levels than those of HC rats, and had a higher hepatic LDL-R
      activity which was 26% higher than that of HC rats. These finding suggested: (1)
      LDL-R activity may be regulated downward in cholesterol-loaded rats; (2) Exercise
      may enhance the utilization and degradation of intracellular cholesterol, and may
      have a feedback effect on the down-regulated synthesis of LDL-R, thus increase
      the uptake of LDL-C and lower plasma level of lipid.

PMID- 10074303
TI  - [Effects of chronic hypoxia on the expression of oncogene jun fos and myb mRNA in
      rat lung].
AB  - This paper is to investigate the expression of oncogene jun fos and myb mRNA in
      the lung of rats exposed to chronic hypoxia. 15 SD rats were put in low oxygen
      chamber (FiO2 = 0.1), 8 hrs daily for 1, 2 and 3 weeks. Five rats breathing room
      air served as control. Oncogene expression in lung tissue assessed by the use of
      in situ hybridization. The results showed that (1) there was a slight expression
      of jun mRNA but not fos and myb mRNA in the control normoxic rats' lung; (2) it
      was found that a less expression of jun mRNA in lung after 1 week hypoxia, but
      after 2 week hypoxia jun mRNA elevated again and significantly increased after 3
      week hypoxia as compared with that in normoxia; (3) the oncogene myb mRNA
      expression showed significant increase in 1 and 2 week hypoxia and returned to
      normal status in 3 week hypoxia; (4) after 1 to 3 week hypoxia, a significant
      increased expression of fos mRNA was found as compared with that in normoxia. It
      is suggested hypoxia may induce increased expression of proto-oncogene jun myb
      and fos, which may be related to proliferation of pulmonary arterial smooth
      muscle cells and fibroblasts.

PMID- 10074304
TI  - [The effects of hypoxia on angiotensin II secretion by cultured pulmonary artery
      endothelial cells].
AB  - The alterations of paracrine function of pulmonary arterial endothelial cells
      (PAEC) might play an important role in the development of hypoxic artery
      hypertension (HPAH). To test this hypothesis, the effects of hypoxia on
      angiotensin II (AT II) secretion by new born bovine PAEC were investigated. AT II
      secretion increased significantly when PAECs were incubated under 2.5% O2 hypoxic
      condition for 1.5 h (P < 0.01 vs control). But it decreased from 1.5 h to 12 h
      incubation and increased from 12 h to 48 h incubation under 0% O2 hypoxic
      condition, with significance compared with control group (P < 0.01). NO donor SIN
      1 inhibited but endogenous NO inhibitor L-nitro-arginine promoted AT II secretion
      significantly under both normorxic and hypoxic conditions. It was also found that
      the concentration of cyclic guanine monophosphate in PAEC decreased significantly
      at 24 h incubation in 0% O2. The above results suggest that changes of AT II in
      PAEC may participate in the development of HPAH.

PMID- 10074306
TI  - [Prostacyclin participates in regulation of hypoxic and high CO2 cerebrovascular
      tension].
AB  - By using prostacyclin synthetase inhibitor-indomethacin, the effects of
      prostacyclin in the presence of endothelial cell on hypoxia- and high CO2-induced
      vasodilatation were studied in newborn calf basilar artery strips. The results
      showed that indomethacin had no effects on cerebrovascular tension, but
      attenuated the hypoxia- and high CO2-induced vasodilatation. After destroying the
      endothelial cell, the cerebral vascular dilatation was decreased, and
      indomethacin had no obvious effect on the vascular tension. These results suggest
      that both prostacyclin and endothelial cell are involved in hypoxia- and high CO2
      induced vasodilatation and the former is derived from endothelial cell.

PMID- 10074307
TI  - [N-2-mercaptopropionyl-glycine improves recovery of myocardial stunning after
      reversible regional ischemia in conscious dogs].
AB  - In order to investigate the therapeutic effect of N-2-Mercaptopropionyl-glycine
      (MPG), a scavenger of hydroxyl radical, on postischemic myocardial dysfunction of
      39 conscious unsedated dogs were undergone a 15 min occlusion of left anterior
      descending coronary artery followed by 48 hours of reperfusion. The treated dogs
      (n = 17) received an infusion of MPG (100 mg/kg.h) for 60 minutes (starting 15
      minutes before occlusion) while the control dogs (n = 22) received normal saline.
      The result showed that there were no significant differences between the two
      groups in collateral blood flow determined by radioactive microsphere, occlusion
      vascular bed and hemodynamic variables. Systolic thickening fraction of
      ventricular wall (an index of regional myocardial function) was similar in both
      groups under baseline condition and during ischemia, whereas it (expressed as
      percent of baseline) was considerably greater in treated dogs at 2, 3, 4, 5, 6
      hours of reperfusion. Much more significant recovery was observed in the dogs
      with collateral flow less than 10% in MPG group. The exponential regression
      analysis showed that the lower the collateral flow, the greater the recovery of
      function in treated dogs. It is concluded that MPG improves recovery of
      myocardial function after reversible regional ischemia, especially with lower
      collateral blood flow.

PMID- 10074308
TI  - [Volume loading experiment in dogs with large area infarction of right and left
      ventricles].
AB  - In order to study volume loading effect on large area myocardial infarction (MI)
      in right and left ventricles, large area MI in both ventricles and cardiogenic
      shock in 12 dogs were induced by occluding coronary arteries. Left ventricular
      systolic pressure (LVSP) and +/- dp/dt max. dropped markedly by 54%, 51% and 47%
      respectively, whereas right ventricular systolic pressure (RVSP) and +/- dp/dt
      max. fell by 9%, 25% and 27% respectively. The condition was obviously worse by
      rapid volume loading (dextran, 30 ml/kg, i.v. in 20 min.) in group I (n = 6),
      leading to increased retrograde beat of right ventricle, further decrease of +/-
      dp/dt max. in both ventricles, significant increase of right atrial pressure
      (RAP) and left ventricular and diastolic pressure (LEVDP) (2.9 +/- 0.2 kPa, P <
      0.01 and 5.0 +/- 0.3 kPa, P < 0.001, respectively), and even ventricular
      fibrillation. Shock was reversed by combined treatment of dopamine (10
      micrograms/kg.min) and glyceryl trinitrate (1 microgram/kg.min) in group II (n =
      6) in 30 min, showing evident increase of arterial pressure, cardiac output, LVSP
      and +/- dp/dt max. without rise in RAP and LVEDP.

PMID- 10074310
TI  - [Antagonistic effect of calcitonin gene related peptide on arrhythmia in rats].
AB  - Premature ventricular contraction (PVC), ventricular tachycardia (VT) and
      ventricular fibrillation (VF) were developed by endothelin-1 (ET-1) injected into
      the coronary ostia at the dose of 900 pmol/kg in anesthetized rats. No arrhythmia
      was elicited but blood pressure fell temporarily by calcitonin gene related
      peptide (CGRP), the injection into the coronary ostia. After pretreatment with
      CGRP incidence and severity of arrhythmia decreased at the same ET-1 dose.
      Arrhythmia score in CGRP 1200 pmol/kg + ET-1 group was lower than that in ET-1
      group (P < 0.01). The results revealed that antiarrhythmic effect of CGRP may be
      partially brought about by its antagonistic effect against ET-1 induced
      arrhythmia.

PMID- 10074312
TI  - [Changes in external secretion of the pancreas in morphine-dependent rat].
AB  - The present study was done both in vivo by cannulating pancreatic duct of
      morphine-dependent rats and in vitro using perfused pancreatic slices from
      morphine-dependent rats. The results were as follows: (1) In morphine-dependent
      rat the pancreatic amylase secretion induced by CCK-8 was significantly declined;
      (2) Amylase content of pancreatic tissue in morphine-dependent rats was lower
      than that of normal rats. It is suggested that the synthesis of amylase in
      morphine-dependent rat pancreas may be inhibited.

PMID- 10074314
TI  - [The expression of HSP-70 gene in exocrine pancreas of the rats suffering from
      acute necrotizing pancreatitis].
AB  - With the acute necrotizing pancreatitis rat model induced by giving sodium
      taurocholate, the expression of hsp70 gene was detected in exocrine pancreas
      using Northern hybridization and immunohistochemistry. Nothern hybridization
      analysis showed that the levels of hsp70 gene expression increased and peaked at
      1 h after operation, and declined to the control levels at 8-16 h. In
      immunohistochemistry detection, the staining for HSP70 protein enhanced
      significantly at 1 h, peaked at 2 h, and then decreased, persisting for 16 h or
      longer. The location of the large particle positive signal for HSP70 was in the
      apical region of the acinar cells, while very few signals for HSP70 were observed
      in the basal region, nucleus and acinar lumen. The results suggest that the high
      expression of hsp70 gene in the acinar cells may be involved in the
      transportation of pancrease enzymes synthesized excessively and in the prevention
      of early enzyme activation.

PMID- 10074316
TI  - [RU486 reverses dexamethasone-mediated suppression of IL-2 receptor expressions
      in lymphocytes of rat spleen].
AB  - Experiments were designed to investigate whether glucocorticoid-mediated
      immunosuppression are involved in glucocorticoid receptor activation. It was
      shown that RU486, a blocker of glucocorticoid, reversed dexamethasone (DEX)
      mediated suppression of CD25 antigen expressions on ConA-stimulated lymphocytes,
      as determined with anti-CD25 monoclonal antibody. By means of radioligand binding
      assay, changes in high affinity IL-2 receptor were examined. The data indicated
      that RU486 alone was unable to affect high affinity IL-2 receptor expressions,
      but antagonized DEX-mediated down regulation of high affinity IL-2 receptor on
      cellular surface. The maximal binding capacities of IL-receptor were 10.0 +/-
      0.7, 10.4 +/- 2.1, 6.5 +/- 0.8 and 12.1 +/- 2.7 fmol/10(7) cell respectively in
      four groups of the normal, RU486, DEX, and DEX plus RU486. The results suggest
      that such effects of DEX may be mediated through glucocorticoid receptor in
      lymphocytes.

PMID- 10074317
TI  - [Effects of hepatocyte growth factor on dose- and time-response of DNA synthesis
      in rat hepatocytes in vitro].
AB  - Effects of recombinant human hepatocyte growth factor (r-hHGF) on dose- and time
      response of DNA synthesis were observed by using the method of 3H-TdR
      incorporation into DNA in rat hepatocytes in vitro. The results showed that r
      hHGF was the most potent mitogen for initiating DNA synthesis of hepatocytes, and
      there were dose-dependent increase in the range of 1 ng/ml (10 pmol/L)-10 ng/ml
      (100 pmol/L). The significant effect of r-hHGF was observed even at 1 ng/ml, and
      the maximal stimulatory effect was found at 10 ng/ml, which was 7-fold rise than
      the control. Beyond 10 ng/ml, r-hHGF inhibited hepatocyte DNA synthesis. In
      addition, time-response of r-hHGF on DNA synthesis was observed at 24 h, 48 h, 72
      h and 96 h respectively, 3H-thymidine incorporation was higher than control group
      after 24 hours of incubation with r-hHGF, and reached top at 48 hours. DNA
      synthesis decreased after 72 and 96 hours of incubation with r-hHGF.

PMID- 10074319
TI  - [The role of opioid receptors of arcuate nucleus in cytokine-induced
      hyperthermia].
AB  - The present study is to define the role played by the opioid receptors of ARH in
      the regulation of body temperature. 1 microliter of IL-1 beta (as pyrogen) was
      injected into the ARH of male Sprague-Dawley rat with an automatic
      micromanipulator to induce hyperthermia. 30 minutes prior to the injection of
      pyrogen, the experimental groups were pre-treated with general opioid receptor
      antagonist naloxone (Nal), selective mu, delta, kappa receptor antagonists CTAP,
      NTI, nor-BNI respectively. Controls were pre-treated with saline. The results
      showed that IL-1 beta-induced hyperthermia was blocked by Nal and CTAP,
      suggesting the involvement of, or mediation by, ARH opioid receptors (mainly the
      mu type) in IL-1 beta-induced hyperthermia. The blockade by delta and kappa
      antagonists was not remarkable. Thus their participation in this process is less
      likely. The similarity between the roles of opioid receptors of ARH and POAH in
      IL-1 beta-induced hyperthermia strongly supports the view that ARH may be an
      important component of the thermoregulatory center.

PMID- 10074320
TI  - [Influences of acetylcholine, glutamic acid and GABA on the neuronal firings in
      ventromedial thalamic nucleus].
AB  - In this study, it was shown that the neuronal spontaneous firings of ventromedial
      thalamic nucleus (VM) in rats were increased by acetylcholine (ACH) and glutamic
      acid (GLU) applied microiontophoretically with an intensity-dependent manner.
      Both gamma-animobutyric acid (GABA) and baclofen inhibited the spontaneous
      firings in majority of VM neurons, but the effect of GABA was rapid and short
      lasting, while that of baclofen was slow and long-lasting. GABA could reverse the
      effects of ACH and GLU. The majority of VM neuronal firing rates could be
      enhanced by bicuculine, while atropine and MK801 had little effect. The results
      indicate an important convergence of GLUergic, GABAergic and cholinergic
      activities in the same VM neurons and GABAergic activities tonically inhibit the
      VM neurons.

PMID- 10074322
TI  - [Effect of interleukins on proliferation of cultured rat anterior pituitary
      cells].
AB  - The present study investigated whether IL-1 and IL-6 involved in the control of
      proliferation in cultured anterior pituitary (AP) cells. Primary culture of AP
      cell were obtained from either male and female Sprague-Dawley rats. The effects
      of IL-1 and IL-6 assessed by [3H]-thymidine incorporation rate. It was found
      that: (1) IL-1(1-100 ng/ml) stimulated 3H-TdR incorporation into AP cells of male
      and female rats. (2) The lower concentration of IL-6 (0.1 ng/ml) inhibited 3H-TdR
      incorporation rate, but higher concentration of IL-6 (1-10 ng/ml) stimulated 3H
      TdR incorporation into AP cells of male rats. (3) IL-6 (0.1-10 ng/ml) stimulated
      3H-TdR incorporation into AP cells of female rats. These results indicated that
      IL-1 and IL-6 can modulate the endocrine activity as well as the proliferation of
      AP cells.

PMID- 10074324
TI  - [Effects of repeated nicotine uptake on brain inositol levels].
AB  - In the acute experiments, 30 minutes after nicotine was intraperitoneally
      injected at the doses of 0.5, 1.0, 1.0, 2.0, 2.0 mg/kg with 5 min interval, the
      inositol levels were increased in rats cerebral cortex and hippocampus rather
      than striatum. While the inositol level was decreased in rat cerebral cortex 30
      minutes after lithium chloride was given at the dose of 10 mmol/kg. In the
      chronic experiments, after nicotine at the doses of 2.0-5.0 mg/kg was
      subcutaneouly injected twice a day for 14 days the inositol level was increased
      in rat cerebral cortex. In other experiments, nicotine was orally given at the
      dosese of 2.69, 6.26, 11.53 mg/kg.d for 64 days, the inositol level of rat
      cerebral cortex was also increased. These indicated that the effects of nicotine
      on inositol level of rat brain are different from those of lithium chloride, the
      inositol level of rat cerebral cortex can be increased by repeated administration
      of nicotine.

PMID- 10074325
TI  - [Effects of both puerarin and gypsum on the firing of pyrogen-treated
      thermosensitive neurons in the region POAH of anesthetized cats].
AB  - To investigate the possible central mechanism of antipyretic effects of Chinese
      medicines, puerarin and gypsum, the firing rate of thermosensitive neurons in
      preoptic-anterior hypothalamus (POAH) region of 34 cats was recorded by using
      extracellular micro-electrode technigue. Injection of pyrogen caused decrease in
      firing rate of 14 warm-sensitive neurons and increase in firing rate of 11 cold
      sensitive neurons in the region of POAH. The effects could be reversed by the
      injection of puerarin and gypsum. The results showed the antipyretic action of
      puerarin and gypsum might be mediated by influences on the electroactivity of
      pyrogen-treated thermosensitive neurons in the region of POAH. Effect of puerarin
      and gypsum on cold-sensitive neurons was stronger than that of single one,
      suggesting that both are synergic in central level.

PMID- 10074326
TI  - [Effect of stimulation of the superior and inferior spermatic nerves on
      testosterone secretion and testicular blood flow].
AB  - The effects of testicular nerves on regulation of androgen secretion were
      examined by determining testicular blood flow and testosterone in testicular vein
      at 10 minute interval before, during, and 10, 20, 30 min after stimulation (Pre.
      Est. Post. 10. Post 20. Post 30 respectively) of superior or inferior spermatic
      nerves (SSN or ISN) with 25 Hz high (50-70 V) or low (20-25 V) currency. Blood
      flow and blood samples of the testicular vein were obtained through a cannula in
      left side under anesthesia of pentobarbital sodium. Under the stimulation of SSN,
      blood flow in testicular vein decreased by 44.87% in Est with high voltage
      whereas with low voltage no change appeared in Est but decreased by 27.25% in the
      period of poststimulation; although with high voltage of stimulation of SSN a
      transient fall of testosterone (42.01%) was observed in Est, 2.5 times increase
      of testosterone occurred in the period of poststimulation, meanwhile the
      testosterone rose by 87.33% in Est of SSN stimulation with low voltage and was
      further elevated up to 4 times in post-stimulated period. Unlike the stimulation
      of SSN, there was no influence of stimulating ISN on testosterone with either
      high or low voltage whereas there was significant increase of blood flow (12.31%)
      in the period of Est with high voltage then it tended to decrease after
      stimulation. The present work supported the hypothesis that testicular nerves
      involve in regulation of androgen secretion in testis and provided a strong
      evidence for further investigation of nervous regulation of endocrine in testis.

PMID- 10074328
TI  - [Cultivation of intra-pulmonary arteriolar smooth muscle cell from rabbit].
AB  - By perfusion with trypsin at low concentration, the intra -pulmonary arterioles
      were separated carefully and cut into fine tissue pieces. These pieces were then
      washed with culture medium and used for culture of smooth muscle cells by method
      of adhesion to wall. Cells cultured were typical smooth muscle cells under light
      microscope, electron microscope and immunohistochemical test. The method is
      simple and convenient. It is also applicable to culture of vascular smooth muscle
      cells from other organs and provides ideal materials for vascular
      physiopathologic studies.

PMID- 10074329
TI  - [Study on Servo-null method for direct measurement of microvascular pressure by
      micropuncture technique].
AB  - The dynamic microvascular pressures in the mesentery of spontaneously
      hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were measured
      and recorded by using the Servo-null microvascular pressure measuring system
      (Model 4A, IPM, Inc., San Diego, USA) with glass micropipettes whose tips were
      1.0-5.0 microns in diameter and had been beveled very sharply at an angle of 25
      degree. Microvascular pressures were measured in two groups of microvessels:
      large, 25-45 microns; small, 15-25 microns. Mean microvascular pressures (Pm) of
      large and small arterial microvessels in SHR were 6.0 +/- 7.0 kPa and 4.8 +/- 0.6
      kPa, respectively. In WKY rats, Pm were 4.2 +/- 0.6 kPa and 3.6 +/- 0.6 kPa,
      respectively. Pm of comparable types of arterial microvessels in SHR and WKY rats
      was significantly different. No significant difference of Pm in small venous
      vessels was found between SHR and WKY rats.

PMID- 10074330
TI  - [Determination of airway reactivity in the conscious and unrestrained guinea
      pigs].
AB  - A simple, stable determining system in the conscious and unrestrained guinea pigs
      was established that can quantitatively analyse the airway reactivity (AR). In
      this model, the response to histamine (His) or acetylcholine (ACh) aerosol was
      concentration-dependent with EC50 effective concentration causing 50% animals
      wheezing) of 53.3 mumol/m3 and 269 mumol/m3 respectively.

PMID- 10074332
TI  - [The establishment and evaluation of abdominal aorta thrombosis model in rat].
AB  - An animal model of abdominal aorta thrombosis based on Virchow's thrombosis
      principle was induced by endothelium denudation with a polyethylene catheter
      combining severe stenosis with an aortic constriction in rats. A total of 37 rats
      were involved in thrombosis induction. Among them thrombus developed in 27 rats.
      Mean length of thrombus was 8.53 +/- 1.42 mm. The contractibility of vascular
      wall in the thrombotic group significantly reduced.

PMID- 10074334
TI  - [Dynamic changes of brainstem auditory evoked potential and the protective effect
      of Piper Wallchii Hand-Mazz during brainstem ischemia in dogs].

PMID- 10074335
TI  - [Changes of the contents of insulin and vasoactive intestinal peptides in the
      patients with primary hypertension].

PMID- 10074336
TI  - [Changes of serum insulin and testosterone contents in Chenshi taijiquan
      exercise].

PMID- 10074337
TI  - Interaction site for high-potential iron-sulfur protein on the tetraheme
      cytochrome subunit bound to the photosynthetic reaction center of Rubrivivax
      gelatinosus.
AB  - We have recently demonstrated, using site-directed mutagenesis, that soluble
      cytochromes interact with the Rubrivivax gelatinosus photosynthetic reaction
      center (RC) in the vicinity of the low-potential heme 1 (c-551, Em = 70 mV) of
      the tetraheme cytochrome subunit, the fourth heme from the special pair of
      bacteriochlorophyll [Osyczka, A., et al. (1998) Biochemistry 37, 11732-11744].
      Although the mutations generated in that study did not show clear effects on the
      electron transfer from high-potential iron-sulfur protein (HiPIP), which is the
      major physiological electron donor to the RC in this bacterium, we report here
      that other site-directed mutations near the solvent-exposed edge of the same low
      potential heme 1, V67K (valine-67 substituted by lysine) and E79K/E85K/E93K
      (glutamates-79, -85, and -93, all replaced by lysines), considerably inhibit the
      electron transfer from HiPIP to the RC. Thus, it is concluded that HiPIP, like
      soluble cytochromes, binds to the RC in the vicinity of the exposed part of the
      low-potential heme 1 of the cytochrome subunit, although some differences in the
      configurations of the HiPIP-RC and cytochrome c-RC transient complexes may be
      postulated.

PMID- 10074338
TI  - Modification of near active site residues in organophosphorus hydrolase reduces
      metal stoichiometry and alters substrate specificity.
AB  - Organophosphorus hydrolase (OPH, EC 8.1.3.1) is a dimeric, bacterial enzyme that
      detoxifies many organophosphorus neurotoxins by hydrolyzing a variety of
      phosphonate bonds. The histidinyl residues at amino acid positions 254 and 257
      are located near the bimetallic active site present in each monomer. It has been
      proposed that these residues influence catalysis by interacting with active site
      residues and the substrate in the binding pocket. We replaced the histidine at
      position 254 with arginine (H254R) and the one at position 257 with leucine
      (H257L) independently to form the single-site-modified enzymes. The double
      modification was also constructed to incorporate both changes (H254R/H257L).
      Although native OPH has two metals at each active site (four per dimer), all
      three of these altered enzymes possessed only two metals per dimer while
      retaining considerable enzymatic activity for the preferred phosphotriester (P-O
      bond) substrate, paraoxon (5-100% kcat). The three altered enzymes achieved a 2
      30-fold increase in substrate specificity (kcat/Km) for demeton S (P-S bond), an
      analogue for the chemical warfare agent VX. In contrast, the substrate
      specificity for diisopropyl fluorophosphonate (P-F bond) was substantially
      decreased for each of these enzymes. In addition, H257L and H254R/H257L showed an
      11- and 18-fold increase, respectively, in specificity for NPPMP, the analogue
      for the chemical warfare agent soman. These results demonstrate the ability to
      significantly enhance the specificity of OPH for various substrates by site
      specific modifications, and it is suggested that changes in metal requirements
      may affect these improved catalytic characteristics by enhancing structural
      flexibility and improving access of larger substrates to the active site, while
      simultaneously decreasing the catalytic efficiency for smaller substrates.

PMID- 10074339
TI  - Aggregation and assembly of phage P22 temperature-sensitive coat protein mutants
      in vitro mimic the in vivo phenotype.
AB  - Aggregation is a common side reaction in the folding of proteins which is likely
      due to inappropriate interactions of folding intermediates. In the in vivo
      folding of phage P22 coat protein, amino acid substitutions that cause a
      temperature-sensitive-folding (tsf) phenotype lead to the localization of the
      mutant coat proteins to inclusion bodies. Investigated here is the aggregation of
      wild-type (WT) coat protein and 3 tsf mutants of coat protein. The tsf coat
      proteins aggregated when refolded in vitro at high temperature. If the tsf coat
      proteins were refolded at 4 degrees C, they were able attain an assembly active
      state. WT coat protein, on the other hand, did not aggregate significantly even
      when folded at high temperature. The refolded tsf mutants exhibited altered
      secondary and tertiary structures and had an increased surface hydrophobicity,
      which may explain the increased propensity of their folding intermediates to
      aggregate.

PMID- 10074340
TI  - Microsecond folding of the cold shock protein measured by a pressure-jump
      technique.
AB  - A pressure-jump apparatus was employed in investigating the kinetics of protein
      unfolding and refolding. In the reaction cell, the pressure can be increased or
      decreased by 100-160 bar within 50-100 microseconds and then held constant. Thus,
      unfolding and refolding reactions in the time range from 70 microseconds to 70 s
      can be followed with this technique. Measurements are possible in the transition
      regions of thermally or denaturant-induced folding in a wide range of
      temperatures and solvent conditions. We used this pressure-jump method to
      determine the temperature dependence of the rate constants of unfolding and
      refolding of the cold shock protein of Bacillus subtilis and of three variants
      thereof with Phe --> Ala substitutions in the central beta-sheet region. For all
      variants, the change in heat capacity occurred in refolding between the unfolded
      and activated states, suggesting that the overall native-like character of the
      activated state of folding was not changed by the deletion of individual Phe side
      chains. The Phe27Ala mutation affected the rate of unfolding only; the Phe15Ala
      and Phe17Ala mutations changed the kinetics of both unfolding and refolding.
      Although the activated state of folding of the cold shock protein is overall
      native-like, individual side chains are still in a non-native environment.

PMID- 10074341
TI  - Stoichiometry of the topa quinone biogenesis reaction in copper amine oxidases.
AB  - The stoichiometry of the topa quinone biogenesis reaction in phenylethylamine
      oxidase from Arthrobacter globiformis (AGAO) has been determined. We have shown
      that the 6e- oxidation of tyrosine to topa quinone (TPQ) consumes 2 mol of O2 and
      produces 1 mol of H2O2/mol of TPQ formed. The rate of H2O2 production is first
      order (kobs = 1.0 +/- 0.2 min-1), a rate only slightly lower than the rate of TPQ
      formation directly determined previously (kobs = 1.5 +/- 0.2 min-1). This gives
      the following net reaction stoichiometry for TPQ biogenesis: E-Tyr + 2O2 --> E
      TPQ + H2O2. This stoichiometry is in agreement with recently proposed mechanisms
      for TPQ biogenesis, and rules out several possible alternatives.

PMID- 10074342
TI  - The activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a
      conserved loop identified by sequence homology, mutagenesis, and limited
      proteolysis.
AB  - Dihydroorotate dehydrogenase catalyzes the oxidation of dihydroorotate to
      orotate. The enzyme from Escherichia coli was overproduced and characterized in
      comparison with the dimeric Lactococcus lactis A enzyme, whose structure is
      known. The two enzymes represent two distinct evolutionary families of
      dihydroorotate dehydrogenases, but sedimentation in sucrose gradients suggests a
      dimeric structure also of the E. coli enzyme. Product inhibition showed that the
      E. coli enzyme, in contrast to the L. lactis enzyme, has separate binding sites
      for dihydroorotate and the electron acceptor. Trypsin readily cleaved the E. coli
      enzyme into two fragments of 182 and 154 residues, respectively. Cleavage reduced
      the activity more than 100-fold but left other molecular properties, including
      the heat stability, intact. The trypsin cleavage site, at R182, is positioned in
      a conserved region that, in the L. lactis enzyme, forms a loop where a cysteine
      residue is very critical for activity. In the corresponding position, the enzyme
      from E. coli has a serine residue. Mutagenesis of this residue (S175) to alanine
      or cysteine reduced the activities 10000- and 500-fold, respectively. The S175C
      mutant was also defective with respect to substrate and product binding.
      Structural and mechanistic differences between the two different families of
      dihydroorotate dehydrogenase are discussed.

PMID- 10074343
TI  - Structural analysis of phospholipase A2 from functional perspective. 1.
      Functionally relevant solution structure and roles of the hydrogen-bonding
      network.
AB  - Bovine pancreatic phospholipase A2 (PLA2), a small (13.8 kDa) Ca2+-dependent
      lipolytic enzyme, is rich in functional and structural character. In an effort to
      examine its detailed structure-function relationship, we determined its solution
      structure by multidimensional nuclear magnetic resonance (NMR) spectroscopy at a
      functionally relevant pH. An ensemble of 20 structures generated has an average
      root-mean-square deviation (RMSD) of 0.62 +/- 0.08 A for backbone (N, Calpha, C)
      atoms and 0.98 +/- 0.09 A for all heavy atoms. The overall structure shows
      several notable differences from the crystal structure: the first three residues
      at the N-terminus, the calcium-binding loop (Y25-T36), and the surface loop (V63
      N72) appear to be flexible; the alpha-helical conformation of helix B (E17-F22)
      is absent; helix D appears to be shorter (D59-V63 instead of D59-D66); and the
      hydrogen-bonding network is less defined. These differences were analyzed in
      relation to the function of PLA2. We then further examined the H-bonding network,
      because its functional role or even its existence in solution has been in dispute
      recently. Our results show that part of the H-bonding network (the portion away
      from N-terminus) clearly exists in solution, as evidenced by direct observation
      (at 11.1 ppm) of a strong H-bond between Y73 and D99 and an implicated
      interaction between D99 and H48. Analyses of a series of mutants indicated that
      the existence of the Y73.D99 H-bond correlates directly with the conformational
      stability of the mutant. Loss of this H-bond results in a loss of 2-3 kcal/mol in
      the conformational stability of PLA2. The unequivocal identification and
      demonstration of the structural importance of a specific hydrogen bond, and the
      magnitude of its contribution to conformational stability, are uncommon to the
      best of our knowledge. Our results also suggest that, while the D99.H48 catalytic
      diad is the key catalytic machinery of PLA2, it also helps to maintain
      conformational integrity.

PMID- 10074344
TI  - Structural analysis of phospholipase A2 from functional perspective. 2.
      Characterization of a molten globule-like state induced by site-specific
      mutagenesis.
AB  - Previous NMR studies have shown that many phospholipase A2 (PLA2, from bovine
      pancreas, overexpressed in Escherichia coli) mutants display some properties
      reminiscent of a molten globule state. Further NMR analyses for some of the
      mutants indicated that formation of the "molten globule-like state" is a pH
      dependent phenomenon. The mutants I9Y and I9F showed perturbed NMR properties
      throughout the pH range studied, while the mutants H48A and C44A/C105A displayed
      native-like spectra at neutral pH but molten globule-like ones under acidic
      conditions, with a "transition pH" around 4. On the other hand, wild-type PLA2
      exhibits exceptional pH stability and turns into a similar molten globule-like
      state only under highly acidic conditions such as 1 M HCl. The H48A mutant was
      used to rigorously establish the property of the molten globule-like state of
      PLA2 mutants. The results of far-UV CD, near-UV CD, and ANS-binding fluorescence
      suggest that H48A retains native-like secondary structures but loses tertiary
      structure during the conformational transition. However, the tertiary structure
      is not completely lost, as evidenced by the retention of some long-range NOEs in
      two-dimensional NOESY spectra. The conclusion was further substantiated by three
      dimensional NOESY-HSQC experiments on a 15N-labeled H48A sample. It was revealed
      that the molten globule-like state at mildly acidic pH retained some rigid
      tertiary structure, which consisted of partial alpha-helix II (Y52-L58), alpha
      helix III (D59-V63), beta-wing (S74-S85) and partial alpha-helix IV (A90-N97).
      These residual tertiary structures grouped in half of the protein could be
      attributed to stabilization by some of the disulfide bonds. The extreme
      sensitivity of the PLA2 structure to site-directed mutagenesis is unprecedented.
      It is interesting to note that most of the functional residues (the active site,
      the hydrophobic channel, the interfacial binding site, and the calcium-binding
      loop) are located in the remainder of the protein, which is well disrupted in
      tertiary interactions.

PMID- 10074345
TI  - Tumor suppressor INK4: determination of the solution structure of p18INK4C and
      demonstration of the functional significance of loops in p18INK4C and p16INK4A.
AB  - Since the structures of several ankyrin-repeat proteins including the INK4
      (inhibitor of cyclin-dependent kinase 4) family have been reported recently, the
      detailed structures and the functional roles of the loops have drawn considerable
      interest. This paper addresses the potential importance of the loops of ankyrin
      repeat proteins in three aspects. First, the solution structure of p18INK4C was
      determined by NMR, and the loop structures were analyzed in detail. The loops
      adapt nascent antiparallel beta-sheet structures, but the positions are slightly
      different from those in the crystal structure. A detailed comparison between the
      solution structures of p16 and p18 has also been presented. The determination of
      the p18 solution structure made such detailed comparisons possible for the first
      time. Second, the [1H,15N]HSQC NMR experiment was used to probe the interactions
      between p18INK4C and other proteins. The results suggest that p18INK4C interacts
      very weakly with dna K and glutathione S-transferase via the loops. The third
      aspect employed site-specific mutagenesis and functional assays. Three mutants of
      p18 and 11 mutants of p16 were constructed to test functional importance of loops
      and helices. The results suggest that loop 2 is likely to be part of the
      recognition surface of p18INK4C or p16INK4A for CDK4, and they provide
      quantitative functional contributions of specific residues. Overall, our results
      enhance understanding of the structural and functional roles of the loops in INK4
      tumor suppressors in particular and in ankyrin-repeat proteins in general.

PMID- 10074346
TI  - Conformational changes in fragments D and double-D from human fibrin(ogen) upon
      binding the peptide ligand Gly-His-Arg-Pro-amide.
AB  - The structure of fragment double-D from human fibrin has been solved in the
      presence and absence of the peptide ligands that simulate the two knobs exposed
      by the removal of fibrinopeptides A and B, respectively. All told, six crystal
      structures have been determined, three of which are reported here for the first
      time: namely, fragments D and double-D with the peptide GHRPam alone and double-D
      in the absence of any peptide ligand. Comparison of the structures has revealed a
      series of conformational changes that are brought about by the various knob-hole
      interactions. Of greatest interest is a moveable "flap" of two negatively charged
      amino acids (Glubeta397 and Aspbeta398) whose side chains are pinned back to the
      coiled coil with a calcium atom bridge until GHRPam occupies the beta-chain
      pocket. Additionally, in the absence of the peptide ligand GPRPam, GHRPam binds
      to the gamma-chain pocket, a new calcium-binding site being formed concomitantly.

PMID- 10074347
TI  - Motion of spin-labeled side chains in T4 lysozyme: effect of side chain
      structure.
AB  - Previous studies have shown that the mobility of nitroxide side chains in a
      protein, inferred from the electron paramagnetic resonance (EPR) spectra, can be
      used to classify particular sites as helix surface sites, tertiary contact sites,
      buried sites, or loop sites. In addition, the sequence dependence of mobility can
      identify regular secondary structure. However, in the most widely used side
      chain, an apparent interaction of the nitroxide ring with the protein at some
      helix surface sites gives rise to EPR spectra degenerate with those at tertiary
      contact sites. In the present study, we use selected sites in T4 lysozyme to
      evaluate novel nitroxide side chains designed to resolve this degeneracy. The
      results indicate that the reagent 3-(methanesulfonylthiomethyl)-2,2, 5,5
      tetramethylpyrrolidin-1-yloxy reacts with cysteine to give a nitroxide side chain
      that has a high contrast in mobility between helix surface and tertiary contact
      sites, effectively resolving the degeneracy. The reagent 3-(iodomercuriomethyl)
      2,2,5,5-tetramethyl-2, 5-dihydro-1H-pyrrol-1-yloxy reacts with cysteine to
      provide a mercury-linked nitroxide that also shows reduced interaction with the
      protein at most helix surface sites. Thus, these new side chains may be the
      preferred choices for structure determination using site-directed spin labeling.

PMID- 10074348
TI  - Stereochemical origin of opposite orientations in DNA adducts derived from
      enantiomeric anti-benzo[a]pyrene diol epoxides with different tumorigenic
      potentials.
AB  - When covalently linked to DNA, enantiomeric pairs of mirror image aromatic diol
      epoxides with differing tumorigenic potencies adopt opposite orientations along
      the DNA helix. This phenomenon has been observed by high-resolution NMR solution
      studies in a number of systems. Preliminary modeling efforts [Geacintov et al.
      (1997) Chem. Res. Toxicol. 10, 111-146) had suggested that the origin of the
      opposite orientation effect may be manifested even at the level of the carcinogen
      modified nucleoside due to primary steric hindrance effects between the aromatic
      moiety and the attached base and sugar. Such a small system can be
      computationally investigated extensively, since a very thorough survey of the
      potential energy surface is feasible. Consequently, in an effort to understand
      the underlying origins of the opposite orientations in (+)-trans and (-)-trans
      anti adduct pairs, we have undertaken an extensive investigation of the paradigm
      10S (+) and 10R (-)-trans-anti-[BP]-N2-dG mononucleoside adduct pair, derived
      from the binding of the (+)-7R,8S,9S,10R and (-)-7S,8R,9R,10S enantiomers of 7,8
      dihydro-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BP) to the exocyclic amino
      group of 2'-deoxyguanosine. In the present work we created 373248 different
      conformers for each adduct, which uniformly sampled the possible rotamers about
      the three flexible torsion angles governing the orientation of the base (chi) and
      its covalently linked BP residue (alpha', beta') at 5 degrees intervals, and
      computed each of their energies with AMBER 4.0. The extensive results permitted
      us to map the potential energy surface of the molecule. Only four low-energy
      structural domains are found for the (+)-trans adduct and four for the (-)-trans
      adduct; the (+)/(-) pairs of each structural domain are mirror images, with the
      mirror image symmetry broken by the sugar and its attached C4'-C5' group. The
      most favored of these four is observed experimentally in the duplexes containing
      the same (+) and (-)-trans-anti-[BP]-N2-dG adducts (Cosman et al. (1992) Proc.
      Natl. Acad. Sci. U.S.A. 89, 1914-1918; de los Santos et al. (1992) Biochemistry
      31, 5245-5252). The origin of the opposite orientations resides in steric
      hindrance effects resulting from the mirror image relationship of the BP benzylic
      rings in the adduct pair, such that rotation of one stereoisomer into the
      conformational domain preferred by the other causes crowding between the base and
      the BP benzylic ring. Limited conformational flexibility in the torsion angle
      beta', the one closest to the bulky BP moiety at the linkage site to guanine,
      plays a key role in governing the orientations in each adduct. The opposite
      orientation phenomenon is likely to manifest itself when the adducts are
      processed by cellular enzymes involved in replication, repair, and transcription
      and thus play a role in the differing biological outcomes stemming from the (+)
      and (-)-trans-anti adducts.

PMID- 10074349
TI  - Intercalation of the (-)-(1R,2S,3R, 4S)-N6-[1-benz[a]anthracenyl]-2'
      deoxyadenosyl adduct in an oligodeoxynucleotide containing the human N-ras codon
      61 sequence.
AB  - The solution structure of the (-)-(1R,2S,3R,4S)-N6-[1-(1,2,3, 4-tetrahydroxy
      benz[a]anthracenyl)]-2'-deoxyadenosyl adduct at X6 of 5'-d(CGGACXAGAAG)-3'.5'
      d(CTTCTTGTCCG)-3', incorporating codons 60, 61(italic), and 62 of the human N-ras
      protooncogene, was determined. This adduct results from the trans opening of
      1S,2R,3R,4S-1, 2-epoxy-1,2,3,4-tetrahydro-benz[a]anthracenyl-3,4-diol by the
      exocyclic N6 of adenine. Molecular dynamics simulations were restrained by 509
      NOEs from 1H NMR. The precision of the refined structures was monitored by
      pairwise root-mean-square deviations which were <1.2 A; accuracy was measured by
      complete relaxation matrix calculations, which yielded a sixth root R factor of
      9.1 x 10(-)2 at 250 ms. The refined structure was a right-handed duplex, in which
      the benz[a]anthracene moiety intercalated from the major groove between C5.G18
      and R,S,R,SA6.T17. In this orientation, the saturated ring of BA was oriented in
      the major groove of the duplex, with the aromatic rings inserted into the duplex
      such that the terminal ring of BA threaded the duplex and faced toward the minor
      groove direction. The duplex suffered localized distortion at and immediately
      adjacent to the adduct site, evidenced by the increased rise of 8.8 A as compared
      to the value of 3.5 A normally observed for B-DNA between base pairs C5.G18 and
      R,S,R,SA6.T17. These two base pairs also buckled in opposite directions away from
      the intercalated BA moiety. The refined structure was similar to the (-)
      (7S,8R,9S,10R)-N6-[10-(7,8,9, 10)-tetrahydrobenzo[a]pyrenyl)]-2'-deoxyadenosyl
      adduct of corresponding stereochemistry at X6 of the same oligodeoxynucleotide
      [Zegar, I. S., Kim, S. J., Johansen, T. N., Horton, P. J., Harris, C. M., Harris,
      T. M., and Stone, M. P. (1996) Biochemistry 35, 6212-6224]. Both adducts
      intercalated toward the 5'-direction from the site of adduction. The similarities
      in solution structures were reflected in similar biological responses, when
      repair-deficient AB2480 Escherichia coli were transformed with M13mp7L2 DNA site
      specifically modified with these two adducts.

PMID- 10074350
TI  - Assembly of an exceptionally stable RNA tertiary interface in a group I ribozyme.
AB  - Group I intron RNAs contain a core of highly conserved helices flanked by
      peripheral domains that stabilize the core structure. In the Tetrahymena group I
      ribozyme, the P4, P5, and P6 helices of the core pack tightly against a three
      helix subdomain called P5abc. Chemical footprinting and the crystal structure of
      the Tetrahymena intron P4-P6 domain revealed that tertiary interactions between
      these two parts of the domain create an extensive solvent-inaccessible interface.
      We have examined the formation and stability of this tertiary interface by
      providing the P5abc segment in trans to a Tetrahymena ribozyme construct that
      lacks P5abc (EDeltaP5abc). Equilibrium gel shift experiments show that the
      affinity of the P5abc and EDeltaP5abc RNAs is exceptionally strong, with a Kd of
      approximately 100 pM at 10 mM MgCl2 (at 37 degrees C). Chemical and enzymatic
      footprinting shows that the RNAs are substantially folded prior to assembly of
      the complex. Solvent accessibility mapping reveals that, in the absence of P5abc,
      the intron RNA maintains a nativelike fold but its active-site helices are not
      tightly packed. Upon binding of P5abc, the catalytic core becomes more tightly
      packed through indirect effects of the tertiary interface formation. This two
      component system facilitates quantitative examination of individual tertiary
      contacts that stabilize the folded intron.

PMID- 10074351
TI  - Mutagenic and enzymological studies of the hydratase and isomerase activities of
      2-enoyl-CoA hydratase-1.
AB  - Structural and enzymological studies have shown the importance of Glu144 and
      Glu164 for the catalysis by 2-enoyl-CoA hydratase-1 (crotonase). Here we report
      about the enzymological properties of the Glu144Ala and Glu164Ala variants of rat
      mitochondrial 2-enoyl-CoA hydratase-1. Size-exclusion chromatography and CD
      spectroscopy showed that the wild-type protein and mutants have similar
      oligomerization states and folding. The kcat values of the active site mutants
      Glu144Ala and Glu164Ala were decreased about 2000-fold, but the Km values were
      unchanged. For study of the potential intrinsic Delta3-Delta2-enoyl-CoA isomerase
      activity of mECH-1, a new assay using 2-enoyl-CoA hydratase-2 and (R)-3
      hydroxyacyl-CoA dehydrogenase as auxiliary enzymes was introduced. It was
      demonstrated that rat wild-type mECH-1 is also capable of catalyzing
      isomerization with the activity ratio (isomerization/hydration) of 1/5000. The
      kcat values of isomerization in Glu144Ala and Glu164Ala were decreased 10-fold
      and 1000-fold, respectively. The data are in line with the proposal that Glu164
      acts as a protic amino acid residue for both the hydration and the isomerization
      reaction. The structural factors favoring the hydratase over the isomerase
      reaction have been addressed by investigating the enzymological properties of the
      Gln162Ala, Gln162Met, and Gln162Leu variants. The Gln162 side chain is hydrogen
      bonded to the Glu164 side chain; nevertheless, these mutants have enzymatic
      properties similar to that of the wild type, indicating that catalytic function
      of the Glu164 side chain in the hydratase and isomerase reaction does not depend
      on the interactions with the Gln162 side chain.

PMID- 10074352
TI  - Equilibrium analyses of the active-site asymmetry in enterococcal NADH oxidase:
      role of the cysteine-sulfenic acid redox center.
AB  - Recent studies [Mallett, T. C., and Claiborne, A. (1998) Biochemistry 37, 8790
      8802] of the O2 reactivity of C42S NADH oxidase (O2 --> H2O2) revealed an
      asymmetric mechanism in which the two FADH2.NAD+ per reduced dimer display
      kinetic inequivalence. In this report we provide evidence indicating that the
      fully active, recombinant wild-type oxidase (O2 --> 2H2O) displays thermodynamic
      inequivalence between the two active sites per dimer. Using NADPH to generate the
      free reduced wild-type enzyme (EH2'/EH4), we have shown that NAD+ titrations lead
      to differential behavior as only one FADH2 per dimer binds NAD+ tightly to give
      the charge-transfer complex. The second FADH2, in contrast, transfers its
      electrons to the single Cys42-sulfenic acid (Cys42-SOH) redox center, which
      remains oxidized during the reductive titration. Titrations of the reduced NADH
      oxidase with oxidized 3-acetylpyridine and 3-aminopyridine adenine dinucleotides
      further support the conclusion that the two FADH2 per dimer in wild-type enzyme
      can be described as distinct "charge-transfer" and "electron-transfer" sites,
      with the latter site giving rise to either intramolecular (Cys42-SOH) or
      bimolecular (pyridine nucleotide) reduction. The reduced C42S mutant is not
      capable of intramolecular electron transfer on binding pyridine nucleotides, thus
      confirming that the Cys42-SOH center is in fact the source of the redox asymmetry
      observed with wild-type oxidase. These observations on the role of Cys42-SOH in
      the expression of thermodynamic inequivalence as observed in wild-type NADH
      oxidase complement the previously described kinetic inequivalence of the C42S
      mutant; taken together, these results provide the overlapping framework for an
      alternating sites cooperativity model of oxidase action.

PMID- 10074353
TI  - Evidence for the direct transfer of the carboxylate of N5-carboxyaminoimidazole
      ribonucleotide (N5-CAIR) to generate 4-carboxy-5-aminoimidazole ribonucleotide
      catalyzed by Escherichia coli PurE, an N5-CAIR mutase.
AB  - Formation of 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) in the purine
      pathway in most prokaryotes requires ATP, HCO3-, aminoimidazole ribonucleotide
      (AIR), and the gene products PurK and PurE. PurK catalyzes the conversion of AIR
      to N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) in a reaction that requires
      both ATP and HCO3-. PurE catalyzes the unusual rearrangement of N5-CAIR to CAIR.
      To investigate the mechanism of this rearrangement, [4,7-13C]-N5-CAIR and [7-14C]
      N5-CAIR were synthesized and separately incubated with PurE in the presence of
      ATP, aspartate, and 4-(N-succinocarboxamide)-5-aminoimidazole ribonucleotide
      (SAICAR) synthetase (PurC). The SAICAR produced was isolated and analyzed by NMR
      spectroscopy or scintillation counting, respectively. The PurC trapping of CAIR
      as SAICAR was required because of the reversibility of the PurE reaction. Results
      from both experiments reveal that the carboxylate group of the carbamate of N5
      CAIR is transferred directly to generate CAIR without equilibration with CO2/HCO3
      in solution. The mechanistic implications of these results relative to the PurE
      only (CO2- and AIR-requiring) AIR carboxylases are discussed.

PMID- 10074354
TI  - The dual biosynthetic capability of N-acetylornithine aminotransferase in
      arginine and lysine biosynthesis.
AB  - The genes encoding the seven enzymes needed to synthesize L-lysine from aspartate
      semialdehyde and pyruvate have been identified in a number of bacterial genera,
      with the single exception of the dapC gene encoding the PLP-dependent N-succinyl
      L, L-diaminopimelate:alpha-ketoglutarate aminotransferase (DapATase).
      Purification of E. coli DapATase allowed the determination of both the amino
      terminal 26 amino acids and a tryptic peptide fragment. Sequence analysis
      identified both of these sequences as being identical to corresponding sequences
      from the PLP-dependent E. coli argD-encoded N-acetylornithine aminotransferase
      (NAcOATase). This enzyme performs a similar reaction to that of DapATase,
      catalyzing the N-acetylornithine-dependent transamination of alpha-ketoglutarate.
      PCR cloning of the argD gene from genomic E. coli DNA, expression, and
      purification yielded homogeneous E. coli NAcOATase. This enzyme exhibits both
      NAcOATase and DapATase activity, with similar specificity constants for N
      acetylornithine and N-succinyl-L,L-DAP, suggesting that it can function in both
      lysine and arginine biosynthesis. This finding may explain why numerous
      investigations have failed to identify genetically the bacterial dapC locus, and
      suggests that this enzyme may be an attractive target for antibacterial inhibitor
      design due to the essential roles of these two pathways in bacteria.

PMID- 10074355
TI  - Proton and electron transfer during the reduction of molecular oxygen by fully
      reduced cytochrome c oxidase: a flow-flash investigation using optical
      multichannel detection.
AB  - Proton and electron transfer events during the reaction of solubilized fully
      reduced bovine heart cytochrome c oxidase with molecular oxygen were investigated
      using the flow-flash technique. Time-resolved spectral changes resulting from
      ligand binding and electron transfer events were detected simultaneously with pH
      changes in the bulk. The kinetics and spectral changes in the visible region (450
      750 nm) were probed by optical multichannel detection, allowing high spectral
      resolution on time scales from 50 ns to 50 ms. Experiments were carried out in
      the presence and absence of pH-sensitive dyes (carboxyfluorescein at pH 6.5,
      phenol red at pH 7.5, and m-cresol purple at pH 8.5) which permitted separation
      of spectral changes due to proton transfer from those caused by ligand binding
      and electron transfer. The transient spectra recorded in the absence of dye were
      analyzed by singular-value decomposition and multiexponential fitting. Five
      apparent lifetimes (0.93 microseconds, 10 microseconds, 36 microseconds, 90
      microseconds, and 1.3 ms at pH 7.5) could consistently be distinguished and
      provided a basis for a reaction mechanism consistent with our most recent kinetic
      model [Sucheta, A., Szundi, I., and Einarsdottir, O. (1999) Biochemistry 37,
      17905-17914]. The dye response indicated that proton uptake occurred concurrently
      with the two slowest electron transfer steps, in agreement with previous results
      based on single-wavelength detection [Hallen, S., and Nilsson, T. (1992)
      Biochemistry 31, 11853-11859]. The stoichiometry of the proton uptake reactions
      was approximately 1.3 +/- 0.3, 1.4 +/- 0.3, and 1.6 +/- 0.5 protons per enzyme at
      pH 6.5, 7.5, and 8.5, respectively. The electron transfer between heme a and CuA
      was limited by proton uptake on a 90 microseconds time scale. We have established
      the lower limit of the true rate constant for the electron transfer between CuA
      and heme a to be approximately 2 x 10(5) s-1.

PMID- 10074356
TI  - Myrothecium verrucaria bilirubin oxidase and its mutants for potential copper
      ligands.
AB  - Bilirubin oxidase (EC:1.3.3.5) purified from a culture medium of Myrothecium
      verrucaria MT-1 (authentic enzyme) catalyzes the oxidation of bilirubin to
      biliverdin in vitro and recombinant enzyme (wild type) was obtained by using an
      overexpression system of the bilirubin oxidase gene with Aspergillus oryzae
      harboring an expression vector. The absorption and ESR spectra showed that both
      bilirubin oxidases are multicopper oxidases containing type 1, type 2, and type 3
      coppers similar to laccase, ascorbate oxidase, and ceruloplasmin. Site-directed
      mutagenesis has been performed for the possible ligands of each type of copper.
      In some mutants, Cys457 --> Val, Ala, His94 --> Val, and His134.136 --> Val, type
      1 and type 2 copper centers were perturbed completely and the enzyme activity was
      completely lost. Differing from the holoenzyme, these mutants showed type 3
      copper signals. However, the optical and magnetic properties characteristic of
      type 1 copper were retained even by mutating one of the type 1 copper ligands,
      i.e., a mutant, Met467 --> Gly, showed a weak but apparent enzyme activity. A
      double mutant His456.458 --> Val had only type 1 Cu, showing a blue band at 600
      nm (epsilon = 1.6 x 10(3)) and an ESR signal with very narrow hyperfine splitting
      (A parallel = 7.2 x 10(-)3 cm-1). Since the type 2 and type 3 coppers are not
      present, the mutant did not show enzyme activity. These results strongly imply
      that the peculiar sequence in bilirubin oxidase, His456-Cys457-His458, forms an
      intramolecular electron-transfer pathway between the type 1 copper site and the
      trinuclear center composed of the type 2 and type 3 copper sites.

PMID- 10074357
TI  - Asn249Tyr substitution at the coenzyme binding domain activates Sulfolobus
      solfataricus alcohol dehydrogenase and increases its thermal stability.
AB  - A mutant of the thermostable NAD+-dependent homotetrameric alcohol dehydrogenase
      from Sulfolobus solfataricus (SsADH), which has a single substitution, Asn249Tyr,
      located at the coenzyme binding domain, was obtained by error prone PCR. The
      mutant enzyme, which was purified from Escherichia coli to homogeneous form,
      exhibits a specific activity that is more than 6-fold greater than that of the
      wild type enzyme, as measured at 65 degrees C with benzyl alcohol as the
      substrate. The oxidation rate of aliphatic alcohols and the reduction rate of
      aromatic aldehydes were also higher. The dissociation constants for NAD+ and NADH
      determined at 25 degrees C and pH 8.8 were 3 orders of magnitude greater compared
      to those of the wild type enzyme. It is thought that the higher turnover of the
      mutant SsADH is due to the faster dissociation of the modified enzyme-coenzyme
      complex. Spectroscopic studies showed no relevant changes in either secondary or
      tertiary structure, while analysis with fluorescent probes revealed a significant
      increase in surface hydrophobicity for the mutant, with respect to that of the
      wild type molecule. The mutant SsADH displays improved thermal stability, as
      indicated by the increase in Tm from 90 to 93 degrees C, which was determined by
      the apparent transition curves. Kinetic thermal stability studies at pH 9.0 for
      mutant SsADH showed a marked increase in activation enthalpy compensated by an
      entropy gain, which resulted in a higher activation barrier against thermal
      unfolding of the enzyme. Ammonia analysis showed that the Asn249Tyr substitution
      produced the effect of markedly reducing the extent of deamidation during
      thermoinactivation, thus suggesting that Asn249 plays a significant role in the
      mechanism of irreversible thermal denaturation of the archaeal ADH. Furthermore,
      the decrease in the activating effect by moderate concentrations of denaturants
      and studies with proteases and chelating agents point to an increase in
      structural rigidity and a tightening of structural zinc as additional factors
      responsible for the improved thermal resistance of the mutant enzyme.

PMID- 10074358
TI  - Exploring the active center of human acetylcholinesterase with stereomers of an
      organophosphorus inhibitor with two chiral centers.
AB  - The stereoselectivity of the phosphonylation reaction and the effects of adduct
      configuration on the aging process were examined for human acetylcholinesterase
      (HuAChE) and its selected active center mutants, using the four stereomers of
      1,2,2-trimethylpropyl methylphosphonofluoridate (soman). The reactivity of wild
      type HuAChE toward the PS-soman diastereomers was 4.0-7.5 x 10(4)-fold higher
      than that toward the PR-diastereomers. Aging of the PSCS-somanyl-HuAChE conjugate
      was also >1.6 x 10(4)-fold faster than that of the corresponding PRCS-somanyl
      adduct, as shown by both reactivation and electrospray mass spectrometry (ESI/MS)
      experiments. On the other hand, both processes exhibited very limited sensitivity
      to the chirality of the alkoxy group Calpha of either PS- or PR-diastereomers.
      These stereoselectivities presumably reflect the relative participation of the
      enzyme in stabilization of the Michaelis complexes and in dealkylation of the
      respective covalent conjugates, and therefore could be utilized for further
      probing of the HuAChE active center functional architecture. Reactivities of
      HuAChE enzymes carrying replacements at the acyl pocket (F295A, F297A, and
      F295L/F297V) indicate that stereoselectivity with respect to the soman phosphorus
      chirality depends on the structure of this binding subsite, but this
      stereoselectivity cannot be explained only by limitation in the capacity to
      accommodate the PR-diastereomers. In addition, these acyl pocket enzyme mutants
      display some (5-10-fold) preference for the PRCR-soman over the PRCS-stereomer,
      while reactivity of the hydrophobic pocket mutant enzyme W86F toward the PRCS
      soman resembles that of the wild type HuAChE. Residue substitutions in the H-bond
      network (E202Q, E450A, Y133F, and Y133A) and the hydrophobic pocket (F338A, W86A,
      W86F, and Y337A) result in a limited stereoselectivity for the PSCS- over the
      PSCR-stereomer. Aging of the PS-somanyl conjugates with all the HuAChE mutant
      enzymes tested practically lacked stereoselectivity with respect to the Calpha of
      the alkoxy moiety. Thus, the inherent asymmetry of the active center does not
      seem to affect the rate-determining step of the dealkylation process, possibly
      because both the PSCS- and the PSCR-somanyl moieties yield the same carbocationic
      intermediate.

PMID- 10074359
TI  - Stabilization of tubulin by deuterium oxide.
AB  - Tubulin is an unstable protein when stored in solution and loses its ability to
      form microtubules rapidly. We have found that D2O stabilizes the protein against
      inactivation at both 4 and 37 degrees C. In H2O-based buffer, tubulin was
      completely inactivated after 40 h at 4 degrees C, but in buffer prepared in D2O,
      no activity was lost after 54 h. Tubulin was completely inactivated at 37 degrees
      C in 8 h in H2O buffer, but only 20% of the activity was lost in D2O buffer.
      Tubulin also lost its colchicine binding activity at a slower rate in D2O. The
      deuterated solvent retarded an aggregation process that occurs during incubation
      at both temperatures. Inactivation in H2O buffer was partially reversed by
      transferring the protein to D2O buffer; however, aggregation was not reversed.
      The level of binding of BisANS, a probe of exposed hydrophobic sites in proteins,
      increases during the inactivation of tubulin. In D2O, the rate of this increase
      is slowed somewhat. We propose that D2O has its stabilizing effect on a
      conformational step or steps that involve the disruption of hydrophobic forces.
      The conformational change is followed by an aggregation process that cannot be
      reversed by D2O. As reported previously [Ito, T., and Sato, H. (1984) Biochim.
      Biophys. Acta 800, 21-27], we found that D2O stimulates the formation of
      microtubules from tubulin. We also observed that the products of assembly in
      D2O/8% DMSO consisted of a high percentage of ribbon structures and incompletely
      folded microtubules. When these polymers were disassembled and reassembled in
      H2O/8% DMSO, the products were microtubules. We suggest that the combination of
      D2O and DMSO, both stimulators of tubulin assembly, leads to the rapid production
      of nuclei that lead to the formation of ribbon structures rather than
      microtubules.

PMID- 10074360
TI  - Tryptophan B27 in the relaxin-like factor (RLF) is crucial for RLF receptor
      binding.
AB  - The relaxin-like factor (RLF) is a circulating hormone that is synthesized in the
      gonads of mammals and released into the bloodstream. The distribution of its
      receptor and a trace of cross-reactivity to relaxin receptors implied that this
      relatively new factor is more relaxin- than insulin-like. The chemical synthesis
      of RLF analogues with specific modifications in positions B27 and B25, or the
      truncated form des(B27-31)RLF, clearly indicate that the intact indole ring in
      position B27 is crucial for high RLF receptor-binding. Receptor-binding was
      reduced by 2 orders of magnitude for Leu(B27)RLF (3%), Ala(B27)RLF (2.1%), and
      des(B27-31)RLF (0.4%), whereas slightly better binding was observed for
      His(B27)RLF (7.5%), Phe(B27)RLF (21%), D-Trp(B27) (26%), and the oxindole(B27)RLF
      (41%). On the basis of these observation it seems that an aromatic ring system in
      the beta- or gamma-position is required for binding. Structure prediction of the
      C-terminal region of the B chain indicated a possible type I or type III turn for
      residues C-G-G-P-R (B22-26) preceding the tryptophan. Exchanging Pro(B25) for D
      Pro within the turn caused a severe structural rearrangement at the C terminus
      and a 96% drop in activity. It appears that the steric effect of L-Pro(B25) is
      important for the proper positioning of Trp(B27).

PMID- 10074361
TI  - Autophosphorylation dependent destabilization of the insulin receptor kinase
      domain: tryptophan-1175 reports changes in the catalytic cleft.
AB  - Protein kinases are regulated by conformational or chemical changes which
      facilitate access of substrates to the active site and promote correct
      orientations of catalytically essential residues and water molecules. The switch
      between basal and activated states of the insulin receptor's kinase domain (IRKD)
      results from autophosphorylation. We investigated the effects of IRKD
      autophosphorylation on the conformational stability by guanidine hydrochloride
      (GdnHCl) dependent denaturation and by iodide quenching of intrinsic
      fluorescence. Tryptophan residues of the recombinant soluble IRKD (residues R953
      S1355) were excited at a lambdaex of 295 nm, and emission spectra were analyzed
      for centroid (a characteristic of average polarity of the indole rings'
      environments) and integrated fluorescence intensity over the lambdaem range of
      310-420 nm. Denaturation profiles of both apo- and phospho-IRKD forms are complex
      with at least three distinct unfolding transitions. The first and last
      transitions were reversible and cooperative and had midpoints at 0.4 or 0.7 M
      GdnHCl and 2.4 or 2.7 M GdnHCl, respectively; transitions of phospho-IRKD
      occurred at lower GdnHCl concentrations. Calculations of free energy of unfolding
      suggested a loss of approximately 2.3 kcal/mol of stabilization for the first
      transition and approximately 1.5 kcal/mol for the third transition. Circular
      dichroism showed subtle changes in secondary structure over the first transition
      and global unfolding over the last transition. The first transition reports
      changes primarily in the local environment of W1175, which is near the catalytic
      loop and is conserved among protein tyrosine kinases. W1175 is also the dominant
      fluorophore of the native emission spectrum. Iodide quenching of W1175 was
      virtually undetectable in the apo-IRKD but significant in the phospho-IRKD,
      suggesting that W1175 exposure to small solutes is strongly dependent on the
      conformation of the activation loop. These studies indicate that
      autophosphorylation, while exposing the catalytic center, also produces a
      conformer less stable than the apoenzyme.

PMID- 10074362
TI  - Interactions of endothelin receptor subtypes A and B with Gi, Go, and Gq in
      reconstituted phospholipid vesicles.
AB  - To understand the biochemical basis for the functional divergence of the human
      endothelin receptor subtypes A (ETAR) and B (ETBR), they were expressed, purified
      from insect Sf9 cells, and reconstituted into phospholipid vesicles with the Go,
      Gq, and Gi proteins. For each G protein, a unique pattern of reactivity was
      observed with the different receptor subtypes. Both ETAR and ETBR activated Go to
      a similar maximal extent, and both subtypes activated Gq with similar EC50
      values; however, the ETAR displayed a 2-3-fold higher maximal extent of
      activation. In contrast, both subtypes activated Gi to a similar maximal extent,
      but the ETAR displayed a 4-fold higher EC50 value as compared to the ETBR. To
      test whether these coupling specificities are influenced by C-terminal
      palmitoylation of the receptor, we mutated a cluster of cysteine residues near
      the end of the seventh transmembrane helix in both receptors. While the cysteine
      mutations in the ETBR resulted in a partially palmitoylated receptor, the
      replacement of these cysteine residues in the ETAR yielded a mostly palmitoyl
      deficient receptor and had no effect on Go activation, but caused a reduction in
      the extents of Gi and Gq stimulation. Together, these studies provide important
      insights into the specificity of G protein coupling in the endothelin receptors.
      The ability to discriminate between the different G proteins under various
      physiological conditions may be a key element in the selection of distinct signal
      transduction pathways by the two receptor subtypes.

PMID- 10074363
TI  - Proximity between periplasmic loops in the lactose permease of Escherichia coli
      as determined by site-directed spin labeling.
AB  - Site-directed thiol cross-linking indicates that the first periplasmic loop (loop
      I/II) in the lactose permease of Escherichia coli is in close proximity to loops
      VII/VIII and XI/XII [Sun, J., and Kaback, H. R. (1997) Biochemistry 36, 11959
      11965]. To determine whether thiol cross-linking reflects proximity as opposed to
      differences in the reactivity and/or dynamics of the Cys residues that undergo
      cross-linking, single-Cys mutants in loops I/II, VII/VIII, and XI/XII and double
      Cys mutants in loop I/II and VII/VIII or XI/XII were purified and labeled with a
      sulfhydryl-specific nitroxide spin label. The labeled mutants were then analyzed
      by electron paramagnetic resonance (EPR) spectroscopy, and interspin distance was
      estimated from the extent of line shape broadening in the double-labeled
      proteins. Out of six paired double-Cys mutants that exhibit thiol cross-linking,
      five display significant spin-spin interaction. Furthermore, there is a
      qualitative correlation between distances estimated by site-directed cross
      linking and EPR. Taken as a whole, the results are consistent with the conclusion
      that site-directed thiol cross-linking is primarily a reflection of proximity.

PMID- 10074364
TI  - Kinetics of activation of the tyrosine kinase of a deletion mutant of epidermal
      growth factor receptor missing the sites of self-phosphorylation.
AB  - The addition of epidermal growth factor (EGF) to epidermal growth factor receptor
      (EGF receptor) dissolved in a solution of the detergent Triton X-100 results in
      the activation of its protein tyrosine kinase. To investigate the importance of
      the sites for self-phosphorylation on the enzyme in this process, the kinetics of
      activation of a deletion mutant missing the last 195 amino acids of the protein,
      including all of the sites for self-phosphorylation, were followed by monitoring
      the initial velocity at which the enzyme catalyzes the phosphorylation of the
      exogenous substrate RRKGSTAENAEYLRV. The activation of the enzymatic activity of
      this deletion mutant of EGF receptor displays kinetics that are second-order with
      respect to the concentration of the enzyme as does wild-type EGF receptor. The
      second-order rate constant for its activation is 36 +/- 10 microM-1 min-1, which
      is only 3-fold greater than the second-order rate constant for the activation of
      wild-type EGF receptor under the same conditions (13 +/- 2 microM-1 min-1). These
      results suggest that the mechanism by which the protein tyrosine kinase of the
      deletion mutant is activated is the same as that for the activation of the wild
      type receptor and that the sites of self-phosphorylation in the wild-type EGF
      receptor do not participate in the mechanism of activation of the enzyme.

PMID- 10074365
TI  - Coordination between Ca2+ release and subsequent re-uptake in the sarcoplasmic
      reticulum.
AB  - We here report the results of our recent effort to produce, in the isolated
      sarcoplasmic reticulum (SR), a biphasic Ca2+ release and Ca2+ re-uptake transient
      and to resolve the kinetic relationship between Ca2+ release and re-uptake of the
      released Ca2+. Ca2+ release from the SR was induced by polylysine (the ryanodine
      receptor-specific Ca2+ release trigger) at various levels of calcium loading, or
      at various doses of the trigger. The changes in the Ca2+ concentration in the
      reaction solution and in the lumenal Ca2+ concentration were determined by
      stopped-flow spectroscopy using fluo-3 and mag-fura-2AM, respectively. At higher
      levels of calcium loading (>150 nmol/mg), polylysine induced monophasic Ca2+
      release curves (without an appreciable re-uptake phase) as reported in most
      studies in the literature. However, lowering the calcium loading level to an
      intermediate range (100-150 nmol/mg) produced the desired biphasic transient
      curves consisting of Ca2+ release and Ca2+ re-uptake phases. Under these
      conditions, the increase in the polylysine concentration resulted in the increase
      of both the rate of Ca2+ release and that of re-uptake of the released Ca2+. The
      maximal rate of Ca2+ release and that of re-uptake showed a parallel relationship
      in the polylysine concentration range of 0-10 microM. This indicates that Ca2+
      release from the SR and re-uptake of the released Ca2+ via the SR Ca2+ pump are
      well-coordinated processes. The changes in the lumenal Ca2+ concentration during
      the release and re-uptake reaction were monitored at an optimum level of calcium
      loading while clamping the extravesicular Ca2+ concentration at a constant value.
      There was again a tight correlation between Ca2+ release (decrease of the lumenal
      Ca2+ concentration) and re-uptake (increase of the lumenal Ca2+ concentration),
      indicating that acceleration of the re-uptake is controlled by the rate of
      decrease of the lumenal Ca2+ concentration. We propose that one of the
      mechanisms, by which the mode of coordination between the two components of the
      biphasic Ca2+ transient (viz. Ca2+ release via the ryanodine receptor and Ca2+ re
      uptake via the SR Ca2+ pump) is controlled, is the change in the Ca2+
      concentration gradient across the SR membrane.

PMID- 10074366
TI  - Helix packing in the lactose permease of Escherichia coli determined by site
      directed thiol cross-linking: helix I is close to helices V and XI.
AB  - Coexpression of lacY gene fragments encoding the first two transmembrane domains
      and the remaining 10 transmembrane domains complement in the membrane and
      catalyze active lactose transport [Wrubel, W., Stochaj, U., et al. (1990) J.
      Bacteriol. 172, 5374-5381]. Accordingly, a plasmid encoding contiguous,
      nonoverlapping permease fragments with a discontinuity in the cytoplasmic loop
      between helices II and III (loop II/III) was constructed (N2C10 permease). When
      Phe27 (helix I) is replaced with Cys, cross-linking is observed with two native
      Cys residues, Cys148 (helix V) and Cys355 (helix XI). Cross-linking of a Cys
      residue at position 27 to Cys148 occurs with N,N'-o-phenylenedimaleimide (o-PDM;
      rigid 6 A), with N,N'-p-phenylenedimaleimide (p-PDM; rigid 10 A), or with 1,6
      bis(maleimido)hexane (BMH; flexible 16 A). On the other hand, with the Phe27-
      >Cys/Cys355 pair, cross-linking is observed with p-PDM or BMH but not o-PDM. In
      neither case is cross-linking observed with iodine. It is suggested that a Cys
      residue at position 27 is within 6-10 A from Cys148 and about 10 A from Cys355.
      The results provide evidence for proximity between helix I and helices V or XI in
      the tertiary structure of the permease. In addition, the findings are consistent
      with other results [Venkatesan, P., Kaback, H. R. (1998) Proc. Natl. Acad. Sci.
      U.S.A. 95, 9802-9807] indicating that Glu126 (helix IV) and Arg144 (helix V) are
      within the membrane, rather than at the membrane-water interface on the
      cytoplasmic face.

PMID- 10074367
TI  - Dynamic modulation of the regulatory domain of myosin heads by pH, ionic
      strength, and RLC phosphorylation in synthetic myosin filaments.
AB  - The position of the myosin head with respect to the filament backbone is thought
      to be a function of pH, ionic strength (micro) and the extent of regulatory light
      chain (RLC) phosphorylation [Harrington (1979) Proc. Natl. Acad. Sci. U.S.A. 76,
      5066-5070]. The object of this study is to examine the dynamics of the proximal
      part of the myosin head (regulatory domain) which accompany the changes in head
      disposition. The essential light chain was labeled at Cys177 with the indanedione
      spin-label followed by the exchange of the labeled proteins into myosin. The
      mobility of the labeled domain was investigated with saturation transfer electron
      paramagnetic resonance in reconstituted, synthetic myosin filaments. We have
      found that the release of the heads from the myosin filament surface by reduction
      of electrostatic charge is accompanied by a 2-fold increase in the mobility of
      the regulatory domain. Phosphorylation of the RLC by myosin light chain kinase
      resulted in a smaller 1. 5-fold increase of motion, establishing that the head
      disordering observed by electron microscopy [Levine et al. (1996) Biophys. J. 71,
      898-907] is due to increased mobility of the heads. This result indirectly
      supports the hypothesis that the RLC phosphorylation effect on potentiation of
      force arises from a release of heads from the filament surface and a shift of the
      heads toward actin.

PMID- 10074368
TI  - Structural characterization by tandem mass spectrometry of the posttranslational
      polyglycylation of tubulin.
AB  - Polyglycylation is a posttranslational modification specific to tubulin. This
      modification was originally identified in highly stable microtubules from
      Paramecium cilia. As many as 34 posttranslationally added glycine residues have
      been located in the C-terminal domains of Paramecium alpha- and beta-tubulin. In
      this study, post source decay matrix-assisted laser desorption/ionization mass
      spectrometry (PSD MALDI MS) and electrospray ionization on a hybrid quadrupole
      orthogonal time-of-flight tandem mass spectrometer (ESI Q-TOF MS/MS) were both
      used to demonstrate that a single molecule of beta-tubulin, from either dynamic
      cytoplasmic microtubules or stable axonemal microtubules, can be glycylated on
      each of the last four C-terminal glutamate residues Glu437, Glu438, Glu439, and
      Glu441 in the sequence 427DATAEEEGEFEEEGEQ442. In both dynamic and stable
      microtubules the most abundant beta-tubulin isoform contains six
      posttranslationally added glycine residues: two glycine residues on both Glu437
      and Glu438 and one glycine residue on both Glu439 and Glu441. The number and
      relative abundance of glycylated isoforms of beta-tubulin in both cytoplasmic and
      axonemal microtubules were compared by MALDI MS.1 The abundance of the major
      glycylated isoforms in axonemal tubulin decreases regularly with glycylation
      levels from 6 to 19 whereas it drops abruptly in cytoplasmic tubulin with
      glycylation levels from 6 to 9. However, the polyglycine chains are similarly
      distributed on the four C-terminal glutamate residues of cytoplasmic and axonemal
      tubulin. The polyglycylation results in bulky C-terminal domains with negatively
      charged surfaces, all surrounding the microtubular structure.

PMID- 10074369
TI  - Synthesis and photochemistry of a photolabile precursor of N-methyl-D-aspartate
      (NMDA) that is photolyzed in the microsecond time region and is suitable for
      chemical kinetic investigations of the NMDA receptor.
AB  - The amino acid L-glutamate is a major neurotransmitter at excitatory synapses
      within the central nervous system. Neuronal responses to glutamate are mediated
      by at least three receptor types, one of which is the NMDA subtype, named for its
      specific ligand N-methyl-D-aspartic acid. Neurotransmitter receptors are
      transmembrane proteins that can form ion channels upon binding a specific ligand
      and are involved in many physiological activities of the brain and in some
      neurological disorders. Elucidating the mechanisms of the formation of
      transmembrane receptor-channels and of receptor regulation and inhibition is
      necessary for understanding nervous system function and for designing potential
      therapeutic agents. This has been hampered by the lack of rapid reaction
      techniques suitable for investigating protein-mediated reactions on cell
      surfaces. Recently a laser-pulse photolysis technique was developed to study the
      chemical reactions of channel-forming receptor proteins in the microsecond-to
      millisecond time region. To apply the technique to NMDA1 receptors a photolabile
      NMDA precursor (beta-DNB NMDA) was synthesized. In this precursor the side chain
      carboxylate was protected as a photosensitive 2,2'-dinitrobenzhydryl ester.
      Photolysis with 308 nm laser light generated free NMDA with a time constant of
      4.2 +/- 0.1 microseconds at pH 7 and a photolysis quantum yield of 0.18 +/- 0.05.
      In rat hippocampal neurons the beta-DNB NMDA (250 microM) neither activated
      endogenously expressed receptors nor potentiated or inhibited the NMDA response.
      Equilibration of hippocampal neurons in the whole-cell current recording mode
      with 250 microM caged precursor followed by a pulse of 333 nm laser light
      resulted in a rapid current rise with a rate constant of 100 s-1 due to opening
      of NMDA-activated receptor-channels. The caged NMDA precursor described here now
      makes it possible to investigate the mechanism of NMDA receptors in the micro- to
      millisecond time region.

PMID- 10074370
TI  - Demonstration by ultraviolet resonance Raman spectroscopy of differences in DNA
      organization and interactions in filamentous viruses Pf1 and fd.
AB  - Pf1, a class II filamentous virus, has been investigated by ultraviolet resonance
      Raman (UVRR) spectroscopy with excitation wavelengths of 257, 244, 238, and 229
      nm. The 257-nm UVRR spectrum is rich in Raman bands of the packaged single
      stranded DNA (ssDNA) genome, despite the low DNA mass (6%) of the virion.
      Conversely, the 229-nm UVRR spectrum is dominated by tyrosines (Tyr 25 and Tyr
      40) of the 46-residue alpha-helical coat subunit. UVRR spectra excited at 244 and
      238 nm exhibit Raman bands diagnostic of both viral DNA and coat protein
      tyrosines. Raman markers of packaged Pf1 DNA contrast sharply with those of the
      DNA packaged in the class I filamentous virus fd [Wen, Z. Q., Overman, S. A., and
      Thomas, G. J., Jr. (1997) Biochemistry 36, 7810-7820]. Interestingly,
      deoxynucleotides of Pf1 DNA exhibit sugars in the C2'-endo/anti conformation and
      bases that are largely unstacked, compared with C3'-endo/anti conformers and very
      strong base stacking in fd DNA; hydrogen-bonding interactions of thymine
      carbonyls are also different in Pf1 and fd. On the other hand, coat protein
      tyrosines of Pf1 exhibit Raman markers of ring environment identical to those of
      fd, including an anomalous singlet at 853 cm-1 in lieu of the canonical Fermi
      doublet (850/830 cm-1) found in globular proteins. The results indicate markedly
      different modes of organization of ssDNA in Pf1 and fd virions, despite similar
      environments for coat protein tyrosines, and suggest strong hydrogen-bonding
      interactions between DNA bases and coat subunits of Pf1 but not between those of
      fd. We propose that structural relationships between the protein coat and
      encapsidated ssDNA genome are also fundamentally different in the two assemblies.

PMID- 10074371
TI  - Unexpected metal ion requirements specific for catalysis of the branching
      reaction in a group II intron.
AB  - The splicing process catalyzed by group II intron ribozymes follows the same two
      step pathway as nuclear pre-mRNA splicing. In vivo, the first splicing step of
      wild-type introns is a transesterification reaction giving rise to a branched
      lariat intron-3'-exon intermediate characteristic of this splicing mode. In the
      wild-type introns, the ribozyme core and the substrate intron-exon junctions are
      carried by the same precursor molecule, making it difficult to distinguish
      between RNA folding and catalysis under normal splicing reactions. To
      characterize the catalytic step of the first transesterification reaction, we
      studied the reversal of this reaction, reverse branching. In this reverse
      reaction, the excised lariat intron and the substrate 5'-exon can be preincubated
      and folded separately, allowing the measure of the catalytic rate of the
      reaction. To measure the catalytic rate of the second splicing step, purified
      lariat intron-3'-exon intermediate molecules were preincubated and folded prior
      to the addition of 5'-exon. Conditions could be found where chemistry appeared
      rate limiting for both catalytic steps. Study of the metal ion requirements under
      these conditions resulted in the unexpected finding that, for the intron studied,
      substitution of magnesium ions by manganese ions enhanced the rate of the first
      transesterification reaction by two orders of magnitude but had virtually no
      effect on the second transesterification reaction or the 5' splice site cleavage
      by hydrolysis. Finally, the catalytic rates measured under optimal conditions for
      both splicing steps were faster by three orders of magnitude in the branching
      pathway than in the hydrolytic pathway.

PMID- 10074372
TI  - Selection and characterization of an RNA decoy for transcription factor NF-kappa
      B.
AB  - Despite their chemical similarity, DNA and RNA sequences typically adopt very
      different structures within cells and are recognized by different proteins.
      However, a few interesting examples of proteins with dual specificity for DNA and
      RNA have previously been noted. These observations raise the possibility that RNA
      surrogates might be identified for many transcription factors that normally bind
      DNA. As an initial test of this novel concept, we used in vitro selection to
      isolate a small RNA aptamer that binds with nanomolar affinity to human
      transcription factor NF-kappa B, a key regulator of inflammation, HIV-1 gene
      expression, and apoptosis. Selected RNAs contain a 31-nucleotide core domain that
      was shown by mutation and deletion analyses to be necessary and sufficient for NF
      kappa B binding. Neither DNA nor 2'-O-methyl RNA analogues of the aptamer bound
      NF-kappa B. The results of competition experiments demonstrate that binding of
      the RNA aptamer blocks the ability of NF-kappa B to bind duplex DNA. Expression
      of this aptamer structure within heterologous nuclear RNA transcripts may provide
      a new strategy to inhibit NF-kappa B function in vivo. Aptamers that inhibit
      transcription factors might be useful in a variety of applications.

PMID- 10074373
TI  - RecA protein of Mycobacterium tuberculosis possesses pH-dependent homologous DNA
      pairing and strand exchange activities: implications for allele exchange in
      mycobacteria.
AB  - To gain insights into inefficient allele exchange in mycobacteria, we compared
      homologous pairing and strand exchange reactions promoted by RecA protein of
      Mycobacterium tuberculosis to those of Escherichia coli RecA protein. The extent
      of single-stranded binding protein (SSB)-stimulated formation of joint molecules
      by MtRecA was similar to that of EcRecA over a wide range of pH values. In
      contrast, strand exchange promoted by MtRecA was inhibited around neutral pH due
      to the formation of DNA networks. At higher pH, MtRecA was able to overcome this
      constraint and, consequently, displayed optimal strand exchange activity. Order
      of addition experiments suggested that SSB, when added after MtRecA, was vital
      for strand exchange. Significantly, with shorter duplex DNA, MtRecA promoted
      efficient strand exchange without network formation in a pH-independent fashion.
      Increase in the length of duplex DNA led to incomplete strand exchange with
      concomitant rise in the formation of intermediates and networks in a pH-dependent
      manner. Treatment of purified networks with S1 nuclease liberated linear duplex
      DNA and products, consistent with a model in which the networks are formed by the
      invasion of hybrid DNA by the displaced linear single-stranded DNA. Titration of
      strand exchange reactions with ATP or salt distinguished a condition under which
      the formation of networks was blocked, but strand exchange was not significantly
      affected. We discuss how these results relate to inefficient allele exchange in
      mycobacteria.

PMID- 10074374
TI  - Thioredoxin reductase from Plasmodium falciparum: evidence for interaction
      between the C-terminal cysteine residues and the active site disulfide-dithiol.
AB  - Thioredoxin reductase (TrxR) catalyzes the reduction of thioredoxin by NADPH.
      TrxR from Plasmodium falciparum (PfTrxR) is a homodimer with a subunit Mr of 59
      000. Each monomer contains one FAD and one redox active disulfide. Despite the
      high degress of similarity between PfTrxR and the human TrxR, their primary
      structures present a striking difference in the C-terminus. PfTrxR has two
      cysteine residues near the C-terminal Gly, while the human TrxR contains a Cys
      SeCys dipeptide penultimate to the C-terminal Gly. It has been proposed that the
      C-terminal cysteines (as a cystine) of PfTrxR are involved in catalysis by an
      intramolecular dithiol-disulfide interchange with the nascent redox active
      dithiol. To investigate the proposed function of the C-terminal cysteines of
      PfTrxR, each has been changed to an alanine [Gilberger, T.-M., Bergmann, B.,
      Walter, R. D., and Muller, S. (1998) FEBS Lett. 425, 407-410]. The single C
      terminal cysteine remaining in each mutant was modified with 5,5'-dithiobis(2
      nitrobenzoic acid) to form mixed disulfides consisting of the enzyme thiol and
      thionitrobenzoate (TNB). In reductive titrations of these mixed disulfide
      enzymes, 1 equiv of TNB anion was released upon reduction of the enzyme itself,
      while control experiments in which mutants without C-terminal cysteine were used
      showed little TNB anion release. This suggests that each of the C-terminal
      cysteines as a TNB mixed disulfide does mimic the proposed electron acceptor in
      the C-terminus. Analysis of the rapid reaction kinetics showed that the C
      terminal mixed disulfide of the modified enzyme is reduced at a rate which is
      comparable with the turnover number of the wild type enzyme.

PMID- 10074375
TI  - Thylakoid protein phosphorylation and the thiol redox state.
AB  - Illumination of thylakoid membranes leads to the phosphorylation of a number of
      photosystem II-related proteins, including the reaction center proteins D1 and D2
      as well as the light-harvesting complex (LHCII). Regulation of light-activated
      thylakoid protein phosphorylation has mainly been ascribed to the redox state of
      the electron carrier plastoquinone. In this work, we show that this
      phosphorylation in vitro is also strongly influenced by the thiol disulfide redox
      state. Phosphorylation of the light-harvesting complex of photosystem II was
      found to be favored by thiol-oxidizing conditions and strongly downregulated at
      moderately thiol-reducing conditions. In contrast, phosphorylation of the
      photosystem II reaction center proteins D1 and D2 as well as that of other
      photosystem II subunits was found to be stimulated up to 2-fold by moderately
      thiol-reducing conditions and kept at a high level also at highly reducing
      conditions. These responses of the level of thylakoid protein phosphorylation to
      changes in the thiol disulfide redox state are reminiscent of those observed in
      vivo in response to changes in the light intensity and point to the possibility
      of a second loop of redox regulation of thylakoid protein phosphorylation via the
      ferredoxin-thioredoxin system.

PMID- 10074376
TI  - Lignin and Mn peroxidase-catalyzed oxidation of phenolic lignin oligomers.
AB  - The oxidation of phenolic oligomers by lignin and manganese peroxidases was
      studied by transient-state kinetic methods. The reactivity of peroxidase
      intermediates compound I and compound II was studied with the phenol guaiacol
      along with a beta-O-4 phenolic dimer, trimer, and tetramer. Compound I of both
      peroxidases is much more reactive than compound II. The rate constants for these
      substrates with Mn peroxidase compound I range from 1.0 x 10(5) M-1 s-1 for
      guaiacol to 1.1 x 10(3) M-1 s-1 for the tetramer. Reactivity is much higher with
      lignin peroxidase compound I with rate constants ranging from 1.2 x 10(6) M-1s-1
      for guaiacol to 3.6 x 10(5) M-1 s-1 for the tetramer. Rate constants with
      compound II are much lower with Mn peroxidase exhibiting very little reactivity.
      The rate constants dramatically decreased with both peroxidases as the size of
      the substrate increased. The extent of the decrease was much more dramatic with
      Mn peroxidase, leading us to conclude that, despite its ability to oxidize
      phenols, Mn2+ is the only physiologically significant substrate. The rate
      decrease associated with increasing substrate size was more gradual with lignin
      peroxidase. These data indicate that whereas Mn peroxidase cannot efficiently
      directly oxidize the lignin polymer, lignin peroxidase is well suited for direct
      oxidation of polymeric lignin.

PMID- 10074377
TI  - Egg white sulfhydryl oxidase: kinetic mechanism of the catalysis of disulfide
      bond formation.
AB  - The flavin-dependent sulfhydryl oxidase from chicken egg white catalyzes the
      oxidation of sulfhydryl groups to disulfides with reduction of oxygen to hydrogen
      peroxide. The oxidase contains FAD and a redox-active cystine bridge and accepts
      a total of 4 electrons per active site. Dithiothreitol (DTT; the best low
      molecular weight substrate known) reduces the enzyme disulfide bridge with a
      limiting rate of 502/s at 4 degrees C, pH 7.5, yielding a thiolate-to-flavin
      charge-transfer complex. Further reduction to EH4 is limited by the slow internal
      transfer of reducing equivalents from enzyme dithiol to oxidized flavin (3.3/s).
      In the oxidative half of catalysis, oxygen rapidly converts EH4 to EH2, but Eox
      appearance is limited by the slow internal redox equilibration. During overall
      turnover with DTT, the thiolate-to-flavin charge-transfer complex accumulates
      with an apparent extinction coefficient of 4.9 mM-1 cm-1 at 560 nm. In contrast,
      glutathione (GSH) is a much slower reductant of the oxidase to the EH2 level and
      shows a kcat/Km 100-fold smaller than DTT. Full reduction of EH2 by GSH shows a
      limiting rate of 3.6/s at 4 degrees C comparable to that seen with DTT. Reduced
      RNase is an excellent substrate of the enzyme, with kcat/Km per thiol some 1000-
      and 10-fold better than GSH and DTT, respectively. Enzyme-monitored steady-state
      turnover shows that RNase is a facile reductant of the oxidase to the EH2 state.
      This work demonstrates the basic similarity in the mechanism of turnover between
      all of these three substrates. A physiological role for sulfhydryl oxidase in the
      formation of disulfide bonds in secreted proteins is discussed.

PMID- 10074378
TI  - Enzymatic H-transfer requires vibration-driven extreme tunneling.
AB  - Enzymatic breakage of the substrate C-H bond by Methylophilus methyltrophus (sp.
      W3A1) methylamine dehydrogenase (MADH) has been studied by stopped-flow
      spectroscopy. The rate of reduction of the tryptophan tryptophylquinone (TTQ)
      cofactor has a large kinetic isotope effect (KIE = 16.8 +/- 0.5), and the KIE is
      independent of temperature. Analysis of the temperature dependence of C-H bond
      breakage revealed that extreme (ground state) quantum tunneling is responsible
      for the transfer of the hydrogen nucleus. Reaction rates are strongly dependent
      on temperature, indicating thermally induced, vibrational motion drives the H
      transfer reaction. The data provide direct experimental evidence for enzymatic
      bond breakage by extreme tunneling driven by vibrational motion of the protein
      scaffold. The results demonstrate that classical transition state theory and its
      tunneling derivatives do not adequately describe this enzymatic reaction.

PMID- 10074379
TI  - Call for papers 

PMID- 10074380
TI  - Emotion and memory: Children's long-term remembering, forgetting, and
      suggestibility.
AB  - Children's memories for an experienced and a never-experienced medical procedure
      were examined. Three- to 13-year-olds were questioned about a voiding
      cystourethrogram fluoroscopy (VCUG) they endured between 2 and 6 years of age.
      Children 4 years or older at VCUG were more accurate than children younger than 4
      at VCUG. Longer delays were associated with providing fewer units of correct
      information but not with more inaccuracies. Parental avoidant attachment style
      was related to increased errors in children's VCUG memory. Children were more
      likely to assent to the false medical procedure when it was alluded to briefly
      than when described in detail, and false assents were related to fewer "do-not
      know" responses about the VCUG. Results have implications for childhood amnesia,
      stress and memory, individual differences, and eyewitness testimony.

PMID- 10074381
TI  - Training phonological awareness with and without explicit attention to
      articulation.
AB  - One hundred twenty-two second- to fifth-grade (7- to 11-year-old) children with
      reading difficulties studied phonological awareness with or without explicit
      attention to articulation and with or without manipulation of sounds. They all
      studied identical phonics and read stories on the computer with speech and
      decoding support for difficult words. Regular-instruction controls received
      regularly scheduled language-arts or reading activities. After 40 h of training,
      children in all three trained conditions outperformed controls on all tests
      except math. Conditions that manipulated sounds showed advantages over the
      condition without explicit practice manipulating sounds, but only on the two
      measures of phonological awareness. Articulatory awareness training yielded no
      unique benefits during this training period. Individual differences in response
      to treatment related to initial levels of phonological awareness, naming speed,
      IQ, and grade. The similar outcomes of the three conditions suggest that specific
      variations in good phonological training may be less important than once thought
      for most children with reading difficulties.

PMID- 10074382
TI  - Gender-linked differences in the incidental memory of children and adults.
AB  - The hunter-gatherer theory (M. Eals & I. Silverman, 1994, Ethology and
      Sociobiology, 15, 95-105) predicts that females should have better incidental
      memory for objects and locations than males. We tested this prediction with 3- to
      6-year-old children (Study 1) and adults (Study 2). In Study 1, 80 children were
      asked to recognize 18 gender-stereotyped toys which they had previously seen in a
      playroom for 2 min. In Study 2, 40 adults were asked to recall the identity and
      location of 30 gender-stereotyped objects which they had previously seen in an
      office for 2 min. Analyses in both studies indicated that females and males
      remembered more toys or objects congruent with their own sex but that there was
      no overall advantage for females. Implications for the hunter-gatherer theory,
      gender-schema theory, and our understanding of the development of incidental
      memory are discussed.

PMID- 10074383
TI  - The paleoenvironment of Sivapithecus parvada.
AB  - Remains of the hominoid Sivapithecus parvada and a diversity of mammalian taxa
      are preserved at locality Y311 (ca. 10 Ma) in the Siwalik Nagri Formation of
      northern Pakistan. Bovids (Bovidae, Artiodactyla) are the most abundant mammals
      next to tragulids (Tragulidae, Artiodactyla) at locality Y311 and provide a means
      for reconstructing the paleoenvironments that would have been available to
      Sivapithecus parvada. A functional model indicates a linkage between habitat and
      several femoral characters among extant bovids. Based on this model, we infer
      that forested habitats predominated at locality Y311 but that some less densely
      covered areas may also have been present. Paleoenvironments in the earlier Chinji
      Formation appear comparable to those at locality Y311, although the presence of a
      continuous canopy in the former is more certain. Thus, adaptive changes in the
      bovid fauna from the Chinji through the Nagri Formations appear to have preceded
      the shift to predominantly C4 grasslands which, based on other lines of evidence,
      occurred locally (and possibly globally) between 8 and 6 Ma. The
      paleoenvironments of locality Y311 and the Chinji Formation localities appear
      different from the paleoenvironment of Kenyapithecus at Fort Ternan in Kenya,
      where the presence of continuous canopy is unlikely. The Fort Ternan fauna is
      dominated by two genera of bovids. One of these is adapted to light cover while
      the other appears better adapted to heavy cover. Sivapithecus and Kenyapithecus
      lived in different ecological settings probably characterized by varying degrees
      of vegetative cover.

PMID- 10074384
TI  - Risk and opportunity for humans coexisting with large carnivores.
AB  - Models of Plio-Pleistocene hominid behavioral ecology often emphasize competition
      with large carnivores. This paper describes competition between modern humans and
      large carnivores in rural Uganda, including active, confrontational scavenging of
      carnivore kills by humans and carnivore attacks on humans. Information gathered
      from Ugandan Game Department archives (1923-1994) reveals that twentieth-century
      agropastoralists regularly tried to scavenge from leopard (Panthera pardus) and
      lion (Panthera leo) kills, and that these large carnivores have preyed on
      hundreds of humans in Uganda over the past several decades. Men were most often
      targets of carnivore attack, particularly while engaged in hunting-related
      activities. However attacks on men were less often lethal than attacks on women
      and children. Analyses show that lion attacks were more dangerous than leopard
      attacks. These data support recent contentions that hominids armed with even
      simple weapons can succeed in active, confrontational scavenging by chasing
      carnivores from kills. Hominids sharing East African habitats with large
      carnivores may have been regularly subject to attack.

PMID- 10074385
TI  - Seasonal variations of the middle-upper paleolithic transition at El castillo,
      Cueva Morin and El pendo (Cantabria, Spain).
AB  - With debate escalating in regard to the prolonged contemporaneity of neandertal
      and modern human groups in the Franco-Cantabrian region on the one hand, and the
      late persistence of neandertals (until ca. 28-30,000 B.P.) and Mousterian
      industries in southern Iberia on the other; sites with Mousterian-Upper
      Paleolithic sequences from northern Spain play a pivotal role in the ongoing
      investigation of the Middle-Upper Paleolithic transition in western Europe. An
      important line of inquiry into the nature of social and economic change from the
      Middle to Upper Paleolithic is the monitoring of shifts in land use and resource
      procurement patterns. The recognition of short-term, seasonal patterning in
      settlement and resource provisioning may provide insights into changes in
      mobility, territoriality, and social organization that might otherwise be missed.
      This paper presents results of a seasonality study of fauna from archaeological
      levels spanning the Middle-Upper Paleolithic transition from the sites of El
      Castillo, El Pendo, and Cueva Morin in Cantabrian Spain. Data concerning season
      of death and age at death of prey animals presented here are derived from dental
      growth mark (increment, annuli) analysis. These data, along with other
      artifactual and faunal evidence suggest to us that: (1) economic strategies and
      technologies pervasive in the Upper Paleolithic are rooted in the Cantabrian
      Middle Paleolithic; and, (2) the apparent increase in deposits from the Middle
      through Upper Paleolithic may be the signature of a gradual increase in
      logistical economic strategies including the heightened level of social
      organization required for their implementation.

PMID- 10074386
TI  - Evolutionary trends of stature in upper Paleolithic and Mesolithic Europe.
AB  - Long bone lengths of all available European Upper Paleolithic (41 males, 25
      females) and Mesolithic (171 males, 118 females) remains have been transformed
      into stature estimates by means of new regression equations derived from Early
      Holocene skeletal samples using "Fully's anatomical stature" and the major axis
      regression technique (Formicola & Franceschi, 1996). Statistical analysis of the
      data, with reference both to time and space parameters, indicates that: (1) Early
      Upper Paleolithic samples (pre-Glacial Maximum) are very tall; (2) Late Upper
      Paleolithic groups (post-Glacial Maximum) from Western Europe, compared to their
      ancestors, show a marked decrease in height; (3) a further, although not
      significant, reduction of stature affects Western Mesolithics; (4) no regional
      differences have been observed during both phases of the Upper Paleolithic; (5) a
      high level of homogeneity has also been found in the Mesolithic, both in Western
      and Eastern Europe; (6) the internal homogeneity found during the Mesolithic in
      Western and Eastern Europe is associated with marked inter-regional variability,
      with populations of the latter region showing systematically significantly
      greater stature than their Western contemporaries. Evaluation of possible causes
      for the great stature of the Early Upper Paleolithic samples points to high
      nutritional standards as the most important factor. Results obtained on later
      groups clearly indicate that the Last Glacial Maximum, rather than the Mesolithic
      transition, is the critical phase in the negative trend affecting Western
      European populations. While changes in the quality of the diet, and in particular
      decreased protein intake, provide a likely explanation for that trend, variations
      in levels of gene flow probably also played a role. Reasons for the West-East
      Mesolithic dichotomy remain unclear and lack of information for the Late Upper
      Paleolithic of Eastern Europe prevents insight into the remote origins of this
      phenomenon. Analysis of regional differentiation of stature, particularly well
      supported by data from Mesolithic sites, points to the absence of today's
      latitudinal gradients and suggests a relative homogeneity in dietary, cultural
      and biodemographic patterns for the last hunter-gatherer populations of Western
      Europe.

PMID- 10074387
TI  - Canine sexing and species number in the Pasalar large hominid sample.

PMID- 10074388
TI  - Conference report: paleoanthropology of the Mani Peninsula (Greece)

PMID- 10074389
TI  - Non-parametric statistical formulas for factors of safety of plant stems 
AB  - A previously proposed statistical approach for computing factors of safety (i.e.
      numerical measures of mechanical reliability) for any load bearing structure,
      like a vertical plant stem, is here extended to cope with organic structures
      whose morphological or mechanical properties have Weibull frequency
      distributions. This approach is illustrated using the actual length L and
      critical buckling length Lerof flower stalks (peduncles) collected from isogenic
      garlic (Allium sativum) populations grown under windy field and protected
      glasshouse conditions. Our analyses of the data indicate that L and Lerof
      peduncles harvested from both populations have Weibull frequency distributions,
      that the factor of safety for glasshouse grown peduncles is very near unity (i.e.
      S=1.03), and that the factor of safety of field grown peduncles is 73% higher
      than that of glasshouse grown plants (i.e. S=1.73). Comparisons between the S 
      values computed on the basis of our formulas and on the basis of the quotient of
      the mean values of Lerand L for each of the two populations indicate that the
      statistical method gives biologically realistic S -values and that the difference
      in the S -values for stems grown under protected and unprotected environmental
      conditions likely reflects the effects of chronic mechanical perturbation (due to
      wind-induced drag) on normal stem growth and development. Copyright 1999 Academic
      Press.

PMID- 10074390
TI  - Evolutionary branching under asymmetric competition.
AB  - I investigate the evolution of a continuous trait, such as body size or arms
      level, which affects the outcome of competitive contests such that the contestant
      with the larger trait value has a higher probability of winning. I show that a
      polymorphism of distinctly different strategies can evolve in an initially
      monomorphic population even if mutations have only small phenotypic effect. In a
      simple Lotka-Volterra-type model of asymmetric competition, I derive the
      conditions under which two strategies can gradually evolve from a single
      ancestral strategy; the evolution of higher level polymorphisms is studied by
      numerical analysis and computer simulations of specific examples. High levels of
      polymorphism may build up during evolution. The coevolution of strategies in
      polymorphic populations, however, may also lead to extinction, which decreases
      the level of polymorphism. I discuss whether the evolution of several haploid
      strategies from a single initial strategy may correspond to the evolution of
      several sympatric species in a diploid outbreeding population.

PMID- 10074391
TI  - Revisited measles and chickenpox dynamics through orthogonal transformation.
AB  - The question addressed is whether or not childhood epidemics such as measles and
      chickenpox are characterized by low-dimensional chaos. We propose a new method
      for the detection and extraction of hidden periodic components embedded in an
      irregular cyclical series, and study the characterization of the epidemiological
      series in terms of the characteristic features or periodicity attributes of the
      extracted components. It is shown that the measles series possesses two periodic
      components each having a period of one year. Both the periodic components have
      time-varying pattern, and the process is nonlinear and deterministic; there is no
      evidence of strong chaoticity in the measles dynamics. The chickenpox series has
      one seasonal component with stable pattern, and the process is deterministic but
      linear, and hence non-chaotic. We also propose surrogate generators based on null
      hypotheses relating to the variability of the periodicity attributes to analyse
      the dynamics in the epidemic series. The process dynamics is also studied using
      seasonally forced SEIR epidemic model, and the characterization performance of
      the proposed schemes is assessed.

PMID- 10074392
TI  - Kinetic models and phenomenological analysis of passive lipid translocation in
      single-file.
AB  - Passive movement of lipids through a membrane-embedded pore is analysed with
      kinetic equations of transport in single-file. The number of lipids arranged
      along the translocation coordinate in the pore is not limited in the
      calculations. The assumption is made that the energetic state of a pore is
      independent of the sequence of lipids contained in it. The results are valid for
      an arbitrary number of species with identical kinetic constants. It is shown that
      infinitely fast diffusion of one vacant site is equivalent to the filled pore
      approximation, which has been used here. We introduce the concept of non-strict
      single-file, which allows also for exchanges of neighbouring lipids inside the
      pore at specified rates. The model successfully simulates the redistribution of
      lipids between the monolayers of red blood cell plasma membranes under operation
      of an active aminophospholipid translocase. Kinetic equations are related to
      linear flux force relations. Phenomenological coefficients are expressed and
      analysed in terms of kinetic constants. Plausible kinetic pore model parameters
      are derived from comparison with a reference simulation of a thermodynamic model
      of the erythrocyte transmembrane lipid distribution. Mechanical forces due to
      differences in compressions of the lipid molecules between the monolayers are
      incorporated in kinetic rate constants. It is seen how the active inward
      transport of aminophospholipids causes an unsymmetrical passive redistribution of
      the other components due to mechanical effects and cross-coupling of fluxes.

PMID- 10074393
TI  - Characterization and comparison of Escherichia coli transfer RNAs by graph theory
      based on secondary structure.
AB  - We have developed a model to characterize the tRNA structures of Escherichia coli
      using graph theory. First of all, tRNAs were represented as graphs, whose
      vertices correspond to nucleotides and the edges to phosphodiester and hydrogen
      bond linkages. Vertices and edges were weighted using the results of a
      preliminary quantum study of the nucleotides and the possible coupling between
      pair bases using the semiempirical method AM1. For each vertex, we defined a
      nucleotide valence that measures the capability of forming hydrogen bonds. Edges
      were differentiated by using bond orders. We have proposed weighted structural
      descriptors-closely related to molecular Randic connectivity and Balaban distance
      indices-as a distinctive characteristic of each structure. Molecules were
      characterized by a set of weighted structural descriptors and classified by a
      clustering method and discriminant function analysis. Two main groups of tRNAs
      that correspond to the biosynthetic amino acid pathways, in agreement with Wong's
      coevolution theory of the genetic code, were obtained.

PMID- 10074394
TI  - On the role of subthreshold dynamics in neuronal signaling.
AB  - The role of subthreshold dynamics in neuronal signaling is examined using
      periodic pulse train stimulation of the Fitzhugh-Nagumo (FN) model of nerve
      membrane excitability and results from the squid giant axon as an experimental
      data base. For a broad range of stimulus conditions the first pulse in a pulse
      train elicited an action potential, whereas all subsequent pulses elicited
      subthreshold responses, both in the axon and in the FN model. These results are
      not well described by the Hodgkin and Huxley 1952 model. Various different
      patterns of subthreshold responses, including chaotic dynamics, can be observed
      in both systems-the FN model and the axon-depending upon stimulus conditions. For
      some conditions action potentials are occasionally interspersed among the
      subthreshold events with randomly occurring interspike intervals. The randomness
      is directly attributable to the underlying subthreshold chaos-deterministic chaos
      rather than to a stochastic noise source. We conclude that this mechanism may
      contribute to multimodal interspike interval histograms which have been observed
      from individual neurons throughout the nervous system.

PMID- 10074395
TI  - Modeling the influence of ectodomain affinities on the spatial distribution of
      membrane receptors.
AB  - We have previously shown that the glycosylphosphatidyl-inositol (GPI)-linked
      urokinase-type plasminogen activator receptor (uPAR) reversibly associates with
      the integrins complement receptor type 3 (CR3; alphaMbeta2) and CR4 (alphaxbeta2)
      during leukocyte motility. These receptor-to-receptor interactions could
      potentially be accounted for by diffusion-controlled reactions or by directed
      transport phenomena. To address these alternatives, we have used computer
      simulation techniques. Our results show that a diffusion-controlled interaction
      between uPAR and CR4 during accumulation at lamellipodia is not physically
      reasonable. This suggests that a directed transport mechanism participates in
      establishing uPAR-integrin association.

PMID- 10074396
TI  - Estimating cell lineage from distributions of randomly introduced markers.
AB  - Cell lineage of a multicellular organism has been analysed by introducing a
      genetic or chemical marker that is inherited from a cell to its daughter cells
      and is detectable even after several cell divisions. To construct a complete cell
      lineage, all the cells at different developmental stages need to be identified,
      and then the intracellular marker must be introduced to each cell. In this paper,
      I study a new method of estimating cell lineage based on distributions of
      intercellular markers observed at a single stage, which are introduced randomly
      at earlier stages. Assumptions are: (1) cell lineage is invariant between
      embryos; (2) a small number of cells are marked in each experiment; and (3) the
      total number of replicate experiments is sufficiently large. Then we identify the
      most likely cell lineage pattern (or tree topology) as the one that requires the
      least marker insertions to be compatible with the observed distributions of cell
      markers. This method is essentially the same as the principle of persimony widely
      used for ancestral phylogeny reconstruction in evolutionary biology. When the
      total number of cells is small, we can generate all the possible cell lineages
      and calculate the minimum number of marker insertions for each candidate, and
      then choose the cell lineage that requires the least marker insertions. If the
      number of cells is large, we can use clustering method in which a pair of cells
      with the highest correlation in marker labelling are merged sequentially. The
      efficiency of the clustering method in estimating the correct cell lineage is
      confirmed by computer simulations. Finally, the clustering method is applied to
      reconstruct the cell lineage of ascidian from experimental data.

PMID- 10074397
TI  - Sex determination in sciarid flies: a model for the control of differential X
      chromosome elimination 
AB  - In sciarids, all zygotes start development with the 3X;2A chromosome
      constitution, two of the three X chromosomes being of paternal origin. The
      elimination of either one or two paternal X chromosomes produces the X:A signal
      which determines development along the female (2X;2A) or male (X0;2A) pathway,
      respectively. A model is proposed in which a chromosomal factor (CF) positively
      interacts with the X chromosome(s) causing its/their elimination. The number of X
      chromosomes to be eliminated is controlled by a maternal factor (MF) which
      regulates the amount of free CF factor interacting with the X chromosomes.
      Imprinting refers to the inability of maternal X chromosomes to bind CF factor.
      Copyright 1999 Academic Press.

PMID- 10074398
TI  - Further evidence relating offspring sex ratios to parental hormone levels around
      the time of conception.

PMID- 10074400
TI  - Magnetic position determination by homing pigeons 

PMID- 10074399
TI  - The magnetic map of homing pigeons: an evergreen phantom 

PMID- 10074401
TI  - Syneretic response to pressure in ocular lens.

PMID- 10074402
TI  - The bromodomain of Gcn5p interacts in vitro with specific residues in the N
      terminus of histone H4.
AB  - Whereas the histone acetyltransferase activity of yeast Gcn5p has been widely
      studied, its structural interactions with the histones and the role of the
      carboxy-terminal bromodomain are still unclear. Using a glutathione S-transferase
      pull down assay we show that Gcn5p binds the amino-terminal tails of histones H3
      and H4, but not H2A and H2B. The deletion of bromodomain abolishes this
      interaction and bromodomain alone is able to interact with the H3 and H4 N
      termini. The amino acid residues of the H4 N terminus involved in the binding
      with Gcn5p have been studied by site-directed mutagenesis. The substitution of
      amino acid residues R19 or R23 of the H4 N terminus with a glutamine (Q)
      abolishes the interaction with Gcn5p and the bromodomain. These residues differ
      from those known to be acetylated or to be involved in binding the SIR proteins.
      This evidence and the known dispensability of the bromodomain for Gcn5p
      acetyltransferase activity suggest a new structural role for the highly
      evolutionary conserved bromodomain.

PMID- 10074403
TI  - Shope fibroma virus DNA topoisomerase catalyses holliday junction resolution and
      hairpin formation in vitro.
AB  - The telomeres of poxviral chromosomes comprise covalently closed hairpin
      structures bearing mismatched bases. These hairpins are formed as concatemeric
      replication intermediates and are processed into mature, unit-length genomes. The
      structural transitions and enzymes involved in telomere resolution are poorly
      understood. Here we show that the type I topoisomerase of Shope fibroma virus
      (SFV) can promote a recombination reaction which converts cloned SFV replication
      intermediates into hairpin-ended molecules resembling mature poxviral telomeres.
      Recombinant SFV topoisomerase linearised a palindromic plasmid bearing 1.5 kb of
      DNA encoding the SFV concatemer junction, at a site near the centre of inverted
      repeat symmetry. Most of these linear reaction products bore hairpin tips as
      judged by denaturing gel electrophoresis. The resolution reaction required
      palindromic SFV DNA sequences and was inhibited by compounds which block branch
      migration (MgCl2) or poxviral topoisomerases. The resolution reaction was also
      slow, needed substantial quantities of topoisomerase, and required that the
      palindrome be extruded in a cruciform configuration. DNA cleavage experiments
      identified a pair of suitably oriented topoisomerase recognition sites, 90 bases
      from the centre of the cloned SFV terminal inverted repeat, which may mark the
      resolution site. These data suggest a resolution scheme in which branch migration
      of a Holliday junction through a site occupied by covalently bound topoisomerase
      molecules, could lead to telomere resolution.

PMID- 10074404
TI  - The simultaneous binding of two double-stranded DNA molecules by Escherichia coli
      RecA protein.
AB  - We have characterized the double-stranded DNA (dsDNA) binding properties of RecA
      protein, using an assay based on changes in the fluorescence of 4',6-diamidino-2
      phenylindole (DAPI)-dsDNA complexes. Here we use fluorescence, nitrocellulose
      filter-binding, and DNase I-sensitivity assays to demonstrate the binding of two
      duplex DNA molecules by the RecA protein filament. We previously established that
      the binding stoichiometry for the RecA protein-dsDNA complex is three base-pairs
      per RecA protein monomer, in the presence of ATP. In the presence of ATPgammaS,
      however, the binding stoichiometry depends on the MgCl2 concentration. The
      stoichiometry is 3 bp per monomer at low MgCl2 concentrations, but changes to 6
      bp per monomer at higher MgCl2 concentrations, with the transition occurring at
      approximately 5 mM MgCl2. Above this MgCl2 concentration, the dsDNA within the
      RecA nucleoprotein complex becomes uncharacteristically sensitive to DNase I
      digestion. For these reasons we suggest that, at the elevated MgCl2 conditions,
      the RecA-dsDNA nucleoprotein filament can bind a second equivalent of dsDNA.
      These results demonstrate that RecA protein has the capacity to bind two dsDNA
      molecules, and they suggest that RecA or RecA-like proteins may effect homologous
      recognition between intact DNA duplexes.

PMID- 10074405
TI  - The antibiotic micrococcin acts on protein L11 at the ribosomal GTPase centre.
AB  - Micrococcin-resistant mutants of Bacillus megaterium that carry mutations
      affecting ribosomal protein L11 have been characterised. The mutants fall into
      two groups. "L11-minus" strains containing an L11 gene with deletions, insertions
      or nonsense mutations which grow 2.5-fold slower than the wild-type strain,
      whereas other mutants carrying single-site substitutions within an 11 amino acid
      residue segment of the N-terminal domain of L11 grow normally. Protein L11 binds
      to 23 S rRNA within the ribosomal GTPase centre which regulates GTP hydrolysis on
      ribosomal factors. Micrococcin binding within the rRNA component of this centre
      was probed on wild-type and mutant ribosomes, in vivo, using dimethyl sulphate
      where it generated an rRNA footprint indistinguishable from that produced in
      vitro, even after the cell growth had been arrested by treatment with either
      kirromycin or fusidic acid. No drug-rRNA binding was detected in vivo for the L11
      minus mutants, while reduced binding (approximately 30-fold) was observed for two
      single-site mutants P23L and P26L. For the latter, the reduced drug affinity
      alone did not account for the resistance-phenotype because rapid cell growth
      occurred even at drug concentrations that would saturate the ribosomes.
      Micrococcin was also bound to complexes containing an rRNA fragment and wild-type
      or mutant L11, expressed as fusion proteins, and they were probed with
      proteinases. The drug produced strong protection effects on the wild-type protein
      and weak effects on the P23L and P26L mutant proteins. We infer that inhibition
      of cell growth by micrococcin, as for thiostrepton, results from the imposition
      of a conformational constraint on protein L11 which, in turn, perturbs the
      function(s) of the ribosomal factor-guanosine nucleotide complexes.

PMID- 10074406
TI  - Intragenic suppression of an active site mutation in the human
      apurinic/apyrimidinic endonuclease.
AB  - The apurinic/apyrimidinic endonucleases (APE) contain several highly conserved
      sequence motifs. The glutamic acid residue in a consensus motif, LQE96TK98 in
      human APE (hAPE-1), is crucial because of its role in coordinating Mg2+, an
      essential cofactor. Random mutagenesis of the inactive E96A mutant cDNA, followed
      by phenotypic screening in Escherichia coli, led to isolation of an intragenic
      suppressor with a second site mutation, K98R. Although the Km of the suppressor
      mutant was about sixfold higher than that of the wild-type enzyme, their kcat
      values were similar for AP endonuclease activity. These results suggest that the
      E96A mutation affects only the DNA-binding step, but not the catalytic step of
      the enzyme. The 3' DNA phosphoesterase activities of the wild-type and the
      suppressor mutant were also comparable. No global change of the protein
      conformation is induced by the single or double mutations, but a local
      perturbation in the structural environment of tryptophan residues may be induced
      by the K98R mutation. The wild-type and suppressor mutant proteins have similar
      Mg2+ requirement for activity. These results suggest a minor perturbation in
      conformation of the suppressor mutant enabling an unidentified Asp or Glu residue
      to substitute for Glu96 in positioning Mg2+ during catalysis. The possibility
      that Asp70 is such a residue, based on its observed proximity to the metal
      binding site in the wild-type protein, was excluded by site-specific mutation
      studies. It thus appears that another acidic residue coordinates with Mg2+ in the
      mutant protein. These results suggest a rather flexible conformation of the
      region surrounding the metal binding site in hAPE-1 which is not obvious from the
      X-ray crystallographic structure.

PMID- 10074407
TI  - Binding properties of the human immunodeficiency virus type 1 nucleocapsid
      protein p7 to a model RNA: elucidation of the structural determinants for
      function.
AB  - HIV-1 nucleocapsid protein (NCp7) is a double zinc-fingered protein that has been
      traditionally implicated in viral RNA recognition and packaging, in addition to
      its tight association with genomic RNA and tRNA primer within the virion
      nucleocapsid. The availability of large quantities of viral or recombinant wild
      type NCp7 and mutant p7 has made possible the assignment of the different roles
      that structural motifs within the protein play during RNA binding. At low ionic
      strength binding to the homopolymeric fluorescent RNA, poly(epsilonA), is
      electrostatically driven and four sodium ions are displaced. Arg7 in the flanking
      N-terminal region, Lys20 and Lys26 in the first zinc finger and one positively
      charged residue (attributed to Lys41) in the second zinc finger are involved in
      electrostatic contacts with RNA. The p7 zinc fingers do not function
      independently but concomitantly. The first zinc finger (both isolated or in the
      context of the full-length protein) has a more prominent electrostatic
      interaction than the second one. The second zinc finger dominates the non
      electrostatic stabilization of the binding to RNA due to stacking of its Trp
      residue with nucleic acid bases. Mutations in the highly conserved retroviral Zn
      coordinating residues (CCHC) to steroid hormone receptor (CCCC) or transcription
      factor (CCHH) metal cluster types do not affect RNA binding. In spite of the
      limited impact in RNA binding affinity in vitro or RNA packaging in vivo that
      such mutations or structural alterations impart, they impair or abolish virus
      infectivity. It is likely that such an effect stems from the involvement of NCp7
      in crucial steps of the virus life cycle other than RNA binding.

PMID- 10074408
TI  - Coevolution and subsite decomposition for the design of resistance-evading HIV-1
      protease inhibitors.
AB  - Drug resistance sharply limits the effectiveness of human immunodeficiency virus
      (HIV) protease inhibitors in acquired immunodeficiency syndrome therapy. In
      previous work, we presented methods for design of resistance-evading inhibitors
      using a computational coevolution technique. Here, we report subsite
      decomposition experiments that examine the relative importance and roles of each
      subsite in HIV protease, and the constraints on robust inhibitor design that are
      imposed by possible resistance mutations in each subsite. The results identify
      several structural features of robust resistance-evading inhibitors for use in
      drug design, and show their basis in the constraints imposed by the range of
      allowable mutation in the protease. In particular, the results identify the P3
      and P3' sites as being particularly sensitive to protease mutation: inhibitors
      designed to fill the S3 and S3' sites of the wild-type protease will be
      susceptible to viral resistance, but inhibitors with side-chains smaller than a
      phenylalanine residue at P3 and P3', preferably medium-sized amino acids in the
      range from valine to leucine and isoleucine residues, will be more robust in the
      face of protease resistance mutation.

PMID- 10074409
TI  - Peptides derived from HIV-1 Vif: a non-substrate based novel type of HIV-1
      protease inhibitors.
AB  - The retroviral protease (PR) is absolutely essential for completion of human
      immunodeficiency virus multiplication cycle, and cannot be replaced by any
      cellular function. Thus PR, like reverse transcriptase, is an ideal target for
      the development of anti-AIDS therapy. A large number of human immunodeficiency
      virus type-1 (HIV-1) PR inhibitors have been developed, and several are currently
      used as anti-AIDS drugs. These inhibitors are mainly based on the natural PR
      cleavage sites within the viral Gag and Gag-Pol precursors. The major difficulty
      encountered while using anti-HIV therapeutic agents in patients has been the
      rapid emergence of drug-resistant viral strains. Most of the mutations which
      convert the PR into inhibitor-resistant are located within the substrate binding
      subsites of the enzyme. Recently, it has been shown that the HIV-1 auxiliary
      protein Vif, and especially the N-terminal half of Vif (N'-Vif) specifically
      interacts with the viral PR and inhibits its activity. We now show that efficient
      inhibition of HIV-1 PR activity can be achieved using Vif-derived peptides. Based
      on the above model we have performed peptide mapping of N'-Vif in order to find a
      small peptidic lead compound which inhibits PR activity. The screening revealed
      that peptides derived from two regions in Vif spanning from residues 30-65 and 78
      98 inhibit PR activity in vitro, specifically bind HIV-PR and inhibit HIV-1
      production in vivo. Further mapping of these regions revealed the lead compounds
      Vif81-88 and Vif88-98. These peptides specifically inhibit and bind HIV-1 PR, but
      do not affect pepsin and rous sarcoma virus protease. In contrast to other known
      PR inhibitors, these peptides are not substrate-based and their sequences do not
      resemble the sequences of the natural PR substrates (cleavage sites). Moreover,
      the Vif-derived peptides themselves are not cleaved by HIV-1 PR. Conversion of
      the lead peptides into small backbone cyclic peptidomimetics is taking place
      nowadays in order to turn these lead compounds into metabolically stable
      selective novel type of HIV-PR non-substrate-based inhibitors.

PMID- 10074410
TI  - Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution.
AB  - Homodimeric bone morphogenetic protein-2 (BMP-2) is a member of the transforming
      growth factor beta (TGF-beta) superfamily that induces bone formation and
      regeneration, and determines important steps during early stages of embryonic
      development in vertebrates and non-vertebrates. BMP-2 can interact with two types
      of receptor chains, as well as with proteins of the extracellular matrix and
      several regulatory proteins. We report here the crystal structure of human BMP-2
      determined by molecular replacement and refined to an R-value of 24.2 % at 2.7 A
      resolution. A common scaffold of BMP-2, BMP-7 and the TGF-betas, i.e. the cystine
      knot motif and two finger-like double-stranded beta-sheets, can be superimposed
      with r. m.s. deviations of around 1 A. In contrast to the TGF-betas, the
      structure of BMP-2 shows differences in the flexibility of the N terminus and the
      orientation of the central alpha-helix as well as two external loops at the
      fingertips with respect to the scaffold. This is also known from the BMP-7 model.
      Small secondary structure elements in the loop regions of BMP-2 and BMP-7 seem to
      be specific for the respective BMP-subgroup. Two identical helix-finger clefts
      and two distinct cavities located around the central 2-fold axis of the dimer
      show characteristic shapes, polarity and surface charges. The possible function
      of these specific features in the interaction of BMP-2 with its binding partners
      is discussed.

PMID- 10074411
TI  - The 9 A projection structure of cytochrome b6f complex determined by electron
      crystallography.
AB  - Thin three-dimensional crystals of the cytochrome b6 f complex from the
      unicellular algae Chlamydomonas reinhardtii have been grown by BioBeads-mediated
      detergent removal from a mixture of protein and lipid solubilized in Hecameg.
      Frozen-hydrated crystals, exhibiting p22121 plane group symmetry, were studied by
      electron crystallography and a projection map at 9 A resolution was calculated.
      The crystals (unit cell dimensions of a=173.5 A, b=70.0 A and gamma=90.0 degrees)
      showed the presence of dimers, and within each monomer 14 domains of electron
      density were observed. The combination of the projection map obtained from ice
      embedded crystals of cytochrome b6 f with a previous map obtained from negatively
      stained samples brings new insight in the organization of the complex. For
      example, it distinguishes some peaks and/or domains that are only extramembrane
      or transmembrane, and reveals the possible localization of single-stranded
      transmembrane alpha-helices (Pet subunits). Furthermore, the cross-correlation of
      our projection map from frozen hydrated samples with the atomic model of the
      transmembrane part of the cytochrome bc1 complex has allowed us to localize the
      cytochrome b6 at the dimer interface and to reveal structural differences between
      the two complexes.

PMID- 10074412
TI  - Side-chain structures in the first turn of the alpha-helix.
AB  - The first three residues at the N terminus of the alpha-helix are called N1, N2
      and N3. We surveyed 2102 alpha-helix N termini in 298 high-resolution, non
      homologous protein crystal structures for N1, N2 and N3 amino acid and side-chain
      rotamer propensities and hydrogen-bonding patterns. We find strong structural
      preferences that are unique to these sites. The rotamer distributions as a
      function of amino acid identity and position in the helix are often explained in
      terms of hydrogen-bonding interactions to the free N1, N2 and N3 backbone NH
      groups. Notably, the "good N2" amino acid residues Gln, Glu, Asp, Asn, Ser, Thr
      and His preferentially form i, i or i,i+1 hydrogen bonds to the backbone, though
      this is hindered by good N-caps (Asp, Asn, Ser, Thr and Cys) that compete for
      these hydrogen bond donors. We find a number of specific side-chain to side-chain
      interactions between N1 and N2 or between the N-cap and N2 or N3, such as Arg(N
      cap) to Asp(N2). The strong energetic and structural preferences found for N1, N2
      and N3, which differ greatly from positions within helix interiors, suggest that
      these sites should be treated explicitly in any consideration of helical
      structure in peptides or proteins.

PMID- 10074413
TI  - Protein conformational changes in the bacteriorhodopsin photocycle.
AB  - We report a comprehensive electron crystallographic analysis of conformational
      changes in the photocycle of wild-type bacteriorhodopsin and in a variety of
      mutant proteins with kinetic defects in the photocycle. Specific intermediates
      that accumulate in the late stages of the photocycle of wild-type
      bacteriorhodopsin, the single mutants D38R, D96N, D96G, T46V, L93A and F219L, and
      the triple mutant D96G/F171C/F219L were trapped by freezing two-dimensional
      crystals in liquid ethane at varying times after illumination with a light flash.
      Electron diffraction patterns recorded from these crystals were used to construct
      projection difference Fourier maps at 3.5 A resolution to define light-driven
      changes in protein conformation. Our experiments demonstrate that in wild-type
      bacteriorhodopsin, a large protein conformational change occurs within
      approximately 1 ms after illumination. Analysis of structural changes in wild
      type and mutant bacteriorhodopsins under conditions when either the M or the N
      intermediate is preferentially accumulated reveals that there are only small
      differences in structure between M and N intermediates trapped in the same
      protein. However, a considerably larger variation is observed when the same
      optical intermediate is trapped in different mutants. In some of the mutants, a
      partial conformational change is present even prior to illumination, with
      additional changes occurring upon illumination. Selected mutations, such as those
      in the D96G/F171C/F219L triple mutant, can sufficiently destabilize the wild-type
      structure to generate almost the full extent of the conformational change in the
      dark, with minimal additional light-induced changes. We conclude that the
      differences in structural changes observed in mutants that display long-lived M,
      N or O intermediates are best described as variations of one fundamental type of
      conformational change, rather than representing structural changes that are
      unique to the optical intermediate that is accumulated. Our observations thus
      support a simplified view of the photocycle of wild-type bacteriorhodopsin in
      which the structures of the initial state and the early intermediates (K, L and
      M1) are well approximated by one protein conformation, while the structures of
      the later intermediates (M2, N and O) are well approximated by the other protein
      conformation. We propose that in wild-type bacteriorhodopsin and in most mutants,
      this conformational change between the M1 and M2 states is likely to make an
      important contribution towards efficiently switching proton accessibility of the
      Schiff base from the extracellular side to the cytoplasmic side of the membrane.

PMID- 10074414
TI  - Site-directed spin-labeling reveals the orientation of the amino acid side-chains
      in the E-F loop of bacteriorhodopsin.
AB  - Due to high temperature factors and the lack of considerable electron density,
      electron microscopy and X-ray experiments on the cytoplasmic E-F loop of
      bacteriorhodopsin result in a variety of structural models. As the experimental
      conditions regarding ionic strength, temperature and the presence of detergents
      may affect the structure of the E-F loop, we employ electron paramagnetic
      resonance and site-directed spin-labeling to study the structure of this loop
      under physiological conditions. The amino acid residues at positions 154 to 171
      were replaced by cysteine residues and derivatized with a sulfhydryl-specific
      nitroxide spin label one by one. The conventional and power saturation electron
      paramagnetic spectroscopy provide the mobility of the nitroxide and its
      accessibility to dissolved molecular oxygen and membrane-impermeable chromium
      oxalate in the respective site. The results show that K159 and A168 are located
      at the water-lipid interface of helices E and F, respectively. The orientation of
      the amino acid side-chains in the helical regions from positions 154 to 159 and
      166 to 171 were found to agree with published structural data for
      bacteriorhodopsin. In the residue sequence from positions 160 to 165 the EPR data
      yield evidence for a turned loop structure with the side-chains of M163 and S162
      oriented towards the proton channel and the water phase, respectively.

PMID- 10074415
TI  - Specialized conservation of surface loops of myosin: evidence that loops are
      involved in determining functional characteristics.
AB  - The molecular motor myosin has been the focus of considerable structure-function
      analysis. Of key interest are the portions of the protein that control the rate
      of ATP hydrolysis, the affinity for actin, and the velocity at which myosin moves
      actin. Two regions that have been implicated in determining these parameters are
      the "loop" regions at the junctions of the 25 kDa and 50 kDa domains and the 50
      kDa and 20 kDa domains of the protein. However, the sequences of these regions
      are poorly conserved between different myosin families, suggesting that they are
      not constrained evolutionarily, and thus are relatively unimportant for myosin
      function. In order to address this apparent incongruity, we have performed an
      analysis of relative rates of observed evolutionary change. We found that the
      sequences of these loop regions appear to be actually more constrained than the
      sequences of the rest of the myosin molecule, when myosins are compared that are
      known to be kinetically or developmentally similar. This suggests that these loop
      regions could play an important role in myosin function and supports the idea
      that they are involved in modulating the specific kinetic characteristics that
      functionally differentiate one myosin isoform from another. Apparently
      "unconserved" loops may generally play a role in determining kinetic properties
      of enzymes, and similar analyses of relative rates of evolution may prove useful
      for the study of structure-function relationships in other protein families.

PMID- 10074416
TI  - Coevolving protein residues: maximum likelihood identification and relationship
      to structure.
AB  - The identification of protein sites undergoing correlated evolution (coevolution)
      is of great interest due to the possibility that these pairs will tend to be
      adjacent in the three-dimensional structure. Identification of such pairs should
      provide useful information for understanding the evolutionary process, predicting
      the effects of site-directed substitution, and potentially for predicting protein
      structure. Here, we develop and apply a maximum likelihood method with the aim of
      improving detection of coevolution. Unlike previous methods which have had
      limited success, this method allows for correlations induced by phylogenetic
      relationships and for variation in rate of evolution along branches, and does not
      rely on accurate reconstruction of ancestral nodes. In order to reduce the
      complexity of coevolutionary relationships and identify the primary component of
      pairwise coevolution between two sites, we reduce the data to a two-state system
      at each site, regardless of the actual number of residues observed at that site.
      Simulations show that this strategy is good at identifying simple correlations
      and at recognizing cases in which the data are insufficient to distinguish
      between coevolution and spurious correlations. The new method was tested by using
      size and charge characteristics to group the residues at each site, and then
      evaluating coevolution in myoglobin sequences. Grouping based on physicochemical
      characteristics allows categorization of coevolving sites into positive and
      negative coevolution, depending on the correlation between equilibrium state
      frequencies. We detected a striking excess of negative coevolution (corresponding
      to charge) at sites brought into proximity by the periodicity of the alpha-helix,
      and there was also a tendency for sites with significant likelihood ratios to be
      close in the three-dimensional structure. Sites on the surface of the protein
      appear to coevolve both when they are close in the structure, and when they are
      distant, implying a role for folding and/or avoidance of quaternary structure in
      the coevolution process.

PMID- 10074418
TI  - Fever: links with an ancient receptor.
AB  - Recent advances have provided evidence that prostaglandin E2 mediates the
      generation of fever in response to interleukin-1 or lipopolysaccharide and have
      reinforced the similarities of signaling downstream of these two pyrogens.

PMID- 10074419
TI  - RNA splicing: more clues from spinal muscular atrophy.
AB  - Spinal muscular atrophy is caused by mutations in the SMN1 gene, the product of
      which is part of a multi-component complex involved in the assembly of small
      nuclear ribonucleoproteins. A recent study indicates that SMN may also play a
      role in pre-mRNA splicing.

PMID- 10074420
TI  - Atomic force microscopy: a forceful way with single molecules.
AB  - The atomic force microscope (AFM) now routinely provides images that reveal
      subnanometer surface structures of biomolecules. The sensitivity and precision of
      AFM provide new opportunities for studying the mechanical properties of
      biomolecules and their interactions in their native environment.

PMID- 10074421
TI  - Molecular chaperones: pathways and networks.
AB  - Some proteins synthesized by growing eukaryotic cells are transferred along
      unidirectional pathways of molecular chaperones until the risk of aggregation has
      decreased and they can be released safely. Mature proteins denatured by stress
      may instead be handled by chaperones acting in branched, reversible networks.

PMID- 10074422
TI  - Is grammar special?
AB  - Recent studies of children with developmental disorders provide striking insights
      into the nature of language. These studies suggest that, although much of
      language arises from more general cognitive capacities, certain aspects of
      grammar have an autonomous psychological and neural basis.

PMID- 10074423
TI  - Light receptor kinases in plants!
AB  - Plants must adapt to a capricious light environment, but the mechanism by which
      light signals are transmitted to cause changes in development has long eluded us.
      The search might be over, however, as two photoreceptors, phytochrome and NPH1,
      have been shown to autophosphorylate in a light-dependent fashion.

PMID- 10074424
TI  - Immune signalling: SHP-2 docks at multiple ports.
AB  - The protein tyrosine phosphatase SHP-2 functions in many diverse signalling
      pathways. The recent identification of a SHP-2-binding protein as a homologue of
      the Grb2-associated adaptor protein Gab1 sheds light on the role of SHP-2 in
      immune signalling.

PMID- 10074425
TI  - A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)
      deficient cells.
AB  - BACKGROUND: The ability of cyclin-dependent kinases (CDKs) to promote cell
      proliferation is opposed by cyclin-dependent kinase inhibitors (CKIs), proteins
      that bind tightly to cyclin-CDK complexes and block the phosphorylation of
      exogenous substrates. Mice with targeted CKI gene deletions have only subtle
      proliferative abnormalities, however, and cells prepared from these mice seem
      remarkably normal when grown in vitro. One explanation may be the operation of
      compensatory pathways that control CDK activity and cell proliferation when
      normal pathways are inactivated. We have used mice lacking the CKIs p21(Cip1) and
      p27(Kip1) to investigate this issue, specifically with respect to CDK regulation
      by mitogens. RESULTS: We show that p27 is the major inhibitor of Cdk2 activity in
      mitogen-starved wild-type murine embryonic fibroblasts (MEFs). Nevertheless,
      inactivation of the cyclin E-Cdk2 complex in response to mitogen starvation
      occurs normally in MEFs that have a homozygous deletion of the p27 gene.
      Moreover, CDK regulation by mitogens is also not affected by the absence of both
      p27 and p21. A titratable Cdk2 inhibitor compensates for the absence of both
      CKIs, and we identify this inhibitor as p130, a protein related to the
      retinoblastoma gene product Rb. Thus, cyclin E-Cdk2 kinase activity cannot be
      inhibited by mitogen starvation of MEFs that lack both p27 and p130. In addition,
      cell types that naturally express low amounts of p130, such as T lymphocytes, are
      completely dependent on p27 for regulation of the cyclin E-Cdk2 complex by
      mitogens. CONCLUSIONS: Inhibition of Cdk2 activity in mitogen-starved fibroblasts
      is usually performed by the CKI p27, and to a minor extent by p21. Remarkably
      p130, a protein in the Rb family that is not related to either p21 or p27, will
      directly substitute for the CKIs and restore normal CDK regulation by mitogens in
      cells lacking both p27 and p21. This compensatory pathway may be important in
      settings in which CKIs are not expressed at standard levels, as is the case in
      many human tumors.

PMID- 10074426
TI  - Identification of a new uracil-DNA glycosylase family by expression cloning using
      synthetic inhibitors.
AB  - BACKGROUND: The cellular environment exposes DNA to a wide variety of endogenous
      and exogenous reactive species that can damage DNA, thereby leading to genetic
      mutations. DNA glycosylases protect the integrity of the genome by catalyzing the
      first step in the base excision-repair of lesions in DNA. RESULTS: Here, we
      report a strategy to conduct genome-wide screening for expressed DNA
      glycosylases, based on their ability to bind to a library of four synthetic
      inhibitors that target the enzyme's active site. These inhibitors, used in
      conjunction with the in vitro expression cloning procedure, led to the
      identification of novel Xenopus and human proteins, xSMUG1 and hSMUG1,
      respectively, that efficiently excise uracil residues from DNA. Despite a lack of
      statistically significant overall sequence similarity to the two established
      classes of uracil-DNA glycosylases, the SMUG1 enzymes contain motifs that are
      hallmarks of a shared active-site structure and overall protein architecture. The
      unusual preference of SMUG1 for single-stranded rather than double-stranded DNA
      suggests a unique biological function in ridding the genome of uracil residues,
      which are potent endogenous mutagens. CONCLUSIONS: The 'proteomics' approach
      described here has led to the isolation of a new family of uracil-DNA
      glycosylases. The three classes of uracil-excising enzymes (SMUG1 being the most
      recently discovered) represent a striking example of structural and functional
      conservation in the almost complete absence of sequence conservation.

PMID- 10074427
TI  - Functional counterparts of mammalian protein kinases PDK1 and SGK in budding
      yeast.
AB  - BACKGROUND: In animal cells, recruitment of phosphatidylinositol 3-kinase by
      growth factor receptors generates 3-phosphoinositides, which stimulate 3
      phosphoinositide-dependent protein kinase-1 (PDK1). Activated PDK1 then
      phosphorylates and activates downstream protein kinases, including protein kinase
      B (PKB)/c-Akt, p70 S6 kinase, PKC isoforms, and serum- and glucocorticoid
      inducible kinase (SGK), thereby eliciting physiological responses. RESULTS: We
      found that two previously uncharacterised genes of Saccharomyces cerevisiae,
      which we term PKH1 and PKH2, encode protein kinases with catalytic domains
      closely resembling those of human and Drosophila PDK1. Both Pkh1 and Pkh2 were
      essential for cell viability. Expression of human PDK1 in otherwise inviable
      pkh1Delta pkh2Delta cells permitted growth. In addition, the yeast YPK1 and YKR2
      genes were found to encode protein kinases each with a catalytic domain closely
      resembling that of SGK; both Ypk1 and Ykr2 were also essential for viability.
      Otherwise inviable ypk1Delta ykr2Delta cells were fully rescued by expression of
      rat SGK, but not mouse PKB or rat p70 S6 kinase. Purified Pkh1 activated
      mammalian SGK and PKBalpha in vitro by phosphorylating the same residue as PDK1.
      Pkh1 activated purified Ypk1 by phosphorylating the equivalent residue (Thr504)
      and was required for maximal Ypk1 phosphorylation in vivo. Unlike PKB, activation
      of Ypk1 and SGK by Pkh1 did not require phosphatidylinositol 3,4,5-trisphosphate,
      consistent with the absence of pleckstrin homology domains in these proteins. The
      phosphorylation consensus sequence for Ypk1 was similar to that for PKBalpha and
      SGK. CONCLUSIONS: Pkh1 and Pkh2 function similarly to PDK1, and Ypk1 and Ykr2 to
      SGK. As in animal cells, these two groups of yeast kinases constitute two tiers
      of a signalling cascade required for yeast cell growth.

PMID- 10074428
TI  - Identification of a new member of the tumor necrosis factor family and its
      receptor, a human ortholog of mouse GITR.
AB  - The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies
      regulate diverse biological functions, including cell proliferation,
      differentiation, and survival [1] [2] [3]. We have identified a new TNF-related
      ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an
      ortholog of the recently discovered murine glucocorticoid-induced TNFR-related
      (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for
      the TNF homolog Fas/CD95 ligand [5]. The hGITR gene mapped to chromosome 1p36,
      near a cluster of five genes encoding TNFR homologs [1] [6]. We found hGITRL mRNA
      in several peripheral tissues, and detected hGITRL protein on cultured vascular
      endothelial cells. The levels of hGITR mRNA in tissues were generally low; in
      peripheral blood T cells, however, antigen-receptor stimulation led to a
      substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in
      embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF
      kappaB, via a pathway that appeared to involve TNFR-associated factor 2 (TRAF2)
      [7] and NF-kappaB-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR
      in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus,
      hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.

PMID- 10074429
TI  - Self-regulated polymerization of the actin-related protein Arp1.
AB  - The actin-related protein Arp1 (or centractin, actin RPV) is the major subunit of
      dynactin, a key component of the cytoplasmic dynein motor machinery [1] [2] [3].
      Of the ubiquitously expressed members of the Arp superfamily, Arp1 is most
      similar to conventional actin [4] [5] [6] and, on the basis of conserved sequence
      features, is predicted to bind ATP and possibly polymerize. In vivo, all
      cytosolic Arp1 sediments at 20S [7] suggesting that it assembles into oligomers,
      most likely dynactin - a multiprotein complex known to contain eight or nine Arp1
      monomers in a 37 nm filament [8]. The uniform length of Arp1 polymers suggests a
      novel assembly mechanism that may be governed by a 'ruler' activity. In dynactin,
      the Arp1 filament is bounded by actin-capping protein at one end and a
      heterotetrameric protein complex containing the p62 subunit (D.M. Eckley, S.R.
      Gill, J.B.B., J.E. Heuser, T.A.S., unpublished observations) at the other [8]. In
      the present study, we analyzed the behavior of highly purified, native Arp1. Arp1
      was found to polymerize rapidly into short filaments that were similar, but not
      identical, in length to those in dynactin. With time, these filaments appeared to
      anneal to form longer assemblies but never attained the length of conventional
      actin filaments.

PMID- 10074430
TI  - Accurate memory for colour but not pattern contrast in chicks.
AB  - The visual displays of animals and plants often look dramatic and colourful to
      us, but what information do they convey to their intended, non-human, audience
      [1] [2]? One possibility is that stimulus values are judged accurately - so, for
      example, a female might choose a suitor if he displays a specific colour [3].
      Alternatively, as for human advertising, displays may attract attention without
      giving information, perhaps by exploiting innate preferences for bright colours
      or symmetry [2] [4] [5]. To address this issue experimentally, we investigated
      chicks' memories of visual patterns. Food was placed in patterned paper
      containers which, like seed pods or insect prey, must be manipulated to extract
      food and their patterns learnt. To establish what was learnt, birds were tested
      on familiar stimuli and on alternative stimuli of differing colour or contrast.
      For colour, birds selected the trained stimulus; for contrast, they preferred
      high contrast patterns over the familiar. These differing responses to colour and
      contrast show how separate components of display patterns could serve different
      roles, with colour being judged accurately whereas pattern contrast attracts
      attention.

PMID- 10074431
TI  - The RLF-B component of the replication licensing system is distinct from Cdc6 and
      functions after Cdc6 binds to chromatin.
AB  - Replication licensing factor (RLF) is an essential initiation factor that can
      prevent re-replication of DNA in a single cell cycle [1] [2]. It is required for
      the initiation of DNA replication, binds to chromatin early in the cell cycle, is
      removed from chromatin as DNA replicates and is unable to re-bind replicated
      chromatin until the following mitosis. Chromatography of RLF from Xenopus
      extracts has shown that it consists of two components termed RLF-B and RLF-M [3].
      The RLF-M component consists of complexes of all six Xenopus minichromosome
      maintenance (MCM/P1) proteins (XMcm2-7), which bind to chromatin in late mitosis
      and are removed as replication occurs [3] [4] [5] [6] [7]. The identity of RLF-B
      is currently unknown. At least two factors must be present on chromatin before
      licensing can occur: the Xenopus origin recognition complex (XORC) [8] [9] and
      Xenopus Cdc6 (XCdc6) [10]. XORC saturates Xenopus sperm chromatin at
      approximately one copy per replication origin whereas XCdc6 binds to chromatin
      only if XORC is bound first [9] [10] [11]. Although XORC has been shown to be a
      distinct activity from RLF-B [9], the relationship between XCdc6 and RLF-B is
      currently unclear. Here, we show that active XCdc6 is loaded onto chromatin in
      extracts with defective RLF, and that both RLF-M and RLF-B are still required for
      the licensing of XCdc6-containing chromatin. Furthermore, RLF-B can be separated
      from XCdc6 by immunoprecipitation and standard chromatography. These experiments
      demonstrate that RLF-B is both functionally and physically distinct from XCdc6,
      and that XCdc6 is loaded onto chromatin before RLF-B function is executed.

PMID- 10074432
TI  - A direct interaction between the adaptor protein Cbl-b and the kinase zap-70
      induces a positive signal in T cells.
AB  - Engagement of the T-cell receptor (TCR)-CD3 complex induces a rapid increase in
      the activities of Src-family and Syk/Zap-70-family kinases [1] [2]. These
      activated kinases then induce the tyrosine phosphorylation of multiple
      intracellular proteins, eventually leading to T-cell activation. One of the
      prominent substrates for these kinases is the adaptor protein Cbl [3] and recent
      studies suggest that Cbl negatively regulates upstream kinases such as Syk and
      Zap-70 [4] [5]. Cbl-b, a homologue of Cbl, is widely expressed in many tissues
      and cells including hematopoietic cells [6] [7]. Cbl-b undergoes rapid tyrosine
      phosphorylation upon stimulation of the TCR and cytokine receptors [8] [9]. The
      role of Cbl-b is unclear, however. Here, we show that overexpression of Cbl-b in
      T cells induced the constitutive activation of the transcription factor nuclear
      factor of activated T cells (NFAT). A loss-of-function mutation in Cbl-b
      disrupted the interaction between Cbl-b and Zap-70 and nearly completely
      abrogated the Cbl-b-mediated activation of NFAT. Unlike the proposed role of Cbl
      as a negative regulator, our results suggest that the Cbl homologue Cbl-b has a
      positive role in T-cell signaling, most likely via a direct interaction with the
      upstream kinase Zap-70.

PMID- 10074433
TI  - The F-box protein beta-TrCP associates with phosphorylated beta-catenin and
      regulates its activity in the cell.
AB  - Defects in beta-catenin regulation contribute to the neoplastic transformation of
      mammalian cells. Dysregulation of beta-catenin can result from missense mutations
      that affect critical sites of phosphorylation by glycogen synthase kinase 3beta
      (GSK3beta). Given that phosphorylation can regulate targeted degradation of beta
      catenin by the proteasome, beta-catenin might interact with an E3 ubiquitin
      ligase complex containing an F-box protein, as is the case for certain cell cycle
      regulators. Accordingly, disruption of the Drosophila F-box protein Slimb
      upregulates the beta-catenin homolog Armadillo. We reasoned that the human
      homologs of Slimb - beta-TrCP and its isoform beta-TrCP2 (KIAA0696) - might
      interact with beta-catenin. We found that the binding of beta-TrCP to beta
      catenin was direct and dependent upon the WD40 repeat sequences in beta-TrCP and
      on phosphorylation of the GSK3beta sites in beta-catenin. Endogenous beta-catenin
      and beta-TrCP could be coimmunoprecipitated from mammalian cells. Overexpression
      of wild-type beta-TrCP in mammalian cells promoted the downregulation of beta
      catenin, whereas overexpression of a dominant-negative deletion mutant
      upregulated beta-catenin protein levels and activated signaling dependent on the
      transcription factor Tcf. In contrast, beta-TrCP2 did not associate with beta
      catenin. We conclude that beta-TrCP is a component of an E3 ubiquitin ligase that
      is responsible for the targeted degradation of phosphorylated beta-catenin.

PMID- 10074434
TI  - Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which
      negatively modulates respiratory organogenesis.
AB  - In Drosophila embryos, the loss of sprouty gene function enhances branching of
      the respiratory system. Three human sprouty homologues (h-Spry1-3) have been
      cloned recently, but their function is as yet unknown [1]. Here, we show that a
      murine sprouty gene (mSpry-2), the product of which shares 97% homology with the
      respective human protein, is expressed in the embryonic murine lung. We used an
      antisense oligonucleotide strategy to reduce expression of mSpry-2 by 96%, as
      measured by competitive reverse transcriptase PCR, in E11. 5 murine embryonic
      lungs cultured for 4 days [2]. Morphologically, the decrease in mSpry-2
      expression resulted in a 72% increase in embryonic murine lung branching
      morphogenesis as well as a significant increase in expression of the lung
      epithelial marker genes SP-C, SP-B and SP-A. These results support a striking
      conservation of function between the Drosophila and mammalian sprouty gene
      families to negatively modulate respiratory organogenesis.

PMID- 10074435
TI  - Primate evolution--in and out of Africa.

PMID- 10074436
TI  - Remembrance of things past...reading.

PMID- 10074437
TI  - Ron Laskey: still discovering new lands.

PMID- 10074439
TI  - One-night mushrooms 

PMID- 10074438
TI  - The Notch proteins.

PMID- 10074440
TI  - Apoptosis: Ras to the rescue in the fly eye.
AB  - Programmed cell death has seemed to be regulated in quite different ways in
      mammals and Drosophila. Recent results on the way Ras and downstream pathways can
      influence cell-death induction suggest the regulatory pathways in these distinct
      organisms might be more similar than was at first sight apparent.

PMID- 10074441
TI  - Stem cells: A tale of two kingdoms.
AB  - Homologous genes have recently been shown to regulate stem cell maintenance in
      animals and plants. This discovery should facilitate elucidation of the poorly
      understood factors that control stem cell maintenance and differentiation.

PMID- 10074442
TI  - Synaptic plasticity: regulated translation in dendrites.
AB  - Synaptic activity can induce neurons to synthesize proteins important for
      cognition and brain development. Recent results suggest this activity-induced
      protein synthesis is partially mediated by regulated translation within neuronal
      dendrites.

PMID- 10074443
TI  - T-cell development: What does Notch do for T cells?
AB  - During their development, T cells are rescued from apoptotic cell death to follow
      distinct lineage fates. Recent data concerned with the role of the Notch
      transmembrane receptor in these events are interpreted to show that Notch
      promotes survival, but contrary to earlier reports has no function in lineage
      commitment.

PMID- 10074444
TI  - Telomeres: structure of a chromosome's aglet.
AB  - Telomeres impart stability on linear eukaryotic chromosomes by acting as caps,
      preventing chromosomes from fusing together or being degraded. The structure of a
      telomere end binding protein in a complex with DNA provides the first molecular
      view of chromosome capping.

PMID- 10074445
TI  - Actin polymerization: Where the WASP stings.
AB  - How do extracellular signals induce actin polymerization, as required for many
      cellular responses? Key signal transducers, such as the small GTPases Cdc42 and
      Rac, have now been shown to link via proteins of the WASP family to the Arp2/3
      complex, which nucleates actin polymerization.

PMID- 10074446
TI  - Bacterial evolution: bacteria play pass the gene.
AB  - DNA transfer between related bacterial species is enhanced by species-specific
      uptake sequences. These sequences have been used to identify genes that have been
      transferred from Haemophilus to Neisseria, providing a clear example of
      interspecific transfer of DNA in the evolution of the pathogenic Neisseria.

PMID- 10074447
TI  - Cortical function: jump-starting the brain.
AB  - Magnetic stimulation as used in studies of the human brain may not merely disrupt
      cognitive functions, but also enhance them. The direction of the effect may
      depend on the frequency of stimulation as much as the area of the brain that is
      stimulated.

PMID- 10074448
TI  - Ion channels: structure of a molecular brake.
AB  - A combination of crystallographic and mutagenesis studies on the HERG K+ channel,
      a key determinant of cardiac excitability, has suggested how the protein's
      extramembraneous amino-terminal domain might act as a 'molecular brake' that
      slows down channel deactivation.

PMID- 10074449
TI  - Reciprocal EGF signaling back to the uterus from the induced C. elegans vulva
      coordinates morphogenesis of epithelia.
AB  - BACKGROUND: Reciprocal signaling between distinct tissues is a general feature of
      organogenesis. Despite the identification of developmental processes in which
      coordination requires reciprocal signaling, little is known regarding the
      underlying molecular details. Here, we use the development of the uterine-vulval
      connection in the nematode Caenorhabditis elegans as a model system to study
      reciprocal signaling. RESULTS: In C. elegans, development of the uterine-vulval
      connection requires the specification of uterine uv1 cells and morphogenesis of 1
      degrees -derived vulval cells. LIN-3, an epidermal growth factor (EGF) family
      protein, is first produced by the gonadal anchor cell to induce vulval precursor
      cells to generate vulval tissue. We have shown that lin-3 is also expressed in
      the 1 degrees vulval lineage after vulval induction and that the 1 degrees vulva
      is necessary to induce the uv1 uterine cell fate. Using genetic and cell
      biological analyses, we found that the specification of uterine uv1 cells is
      dependent on EGF signaling from cells of the 1 degrees vulval lineages to a
      subset of ventral uterine cells of the gonad. RAS and RAF are necessary for this
      signaling. We also found that EGL-38, a member of the PAX family of proteins, is
      necessary for transcription of lin-3 in the vulva but not in the anchor cell. A
      let-23 mutation that confers ligand-independent activity bypasses the requirement
      for EGL-38 in specification of the uv1 cell fate. CONCLUSIONS: We have shown how
      relatively simple EGF signals can be used reciprocally to specify the uterine
      vulval connection during C. elegans development.

PMID- 10074450
TI  - Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase
      Cdc28 and the phosphatase Cdc14.
AB  - BACKGROUND: Exit from mitosis requires inactivation of mitotic cyclin-dependent
      kinases (CDKs). A key mechanism of CDK inactivation is ubiquitin-mediated cyclin
      proteolysis, which is triggered by the late mitotic activation of a ubiquitin
      ligase known as the anaphase-promoting complex (APC). Activation of the APC
      requires its association with substoichiometric activating subunits termed Cdc20
      and Hct1 (also known as Cdh1). Here, we explore the molecular function and
      regulation of the APC regulatory subunit Hct1 in Saccharomyces cerevisiae.
      RESULTS: Recombinant Hct1 activated the cyclin-ubiquitin ligase activity of APC
      isolated from multiple cell cycle stages. APC isolated from cells arrested in G1,
      or in late mitosis due to the cdc14-1 mutation, was more responsive to Hct1 than
      APC isolated from other stages. We found that Hct1 was phosphorylated in vivo at
      multiple CDK consensus sites during cell cycle stages when activity of the cyclin
      dependent kinase Cdc28 is high and APC activity is low. Purified Hct1 was
      phosphorylated in vitro at these sites by purified Cdc28-cyclin complexes, and
      phosphorylation abolished the ability of Hct1 to activate the APC in vitro. The
      phosphatase Cdc14, which is known to be required for APC activation in vivo, was
      able to reverse the effects of Cdc28 by catalyzing Hct1 dephosphorylation and
      activation. CONCLUSIONS: We conclude that Hct1 phosphorylation is a key
      regulatory mechanism in the control of cyclin destruction. Phosphorylation of
      Hct1 provides a mechanism by which Cdc28 blocks its own inactivation during S
      phase and early mitosis. Following anaphase, dephosphorylation of Hct1 by Cdc14
      may help initiate cyclin destruction.

PMID- 10074451
TI  - Delta-mediated specification of midline cell fates in zebrafish embryos.
AB  - BACKGROUND: Fate mapping studies have shown that progenitor cells of three
      vertebrate embryonic midline structures - the floorplate in the ventral neural
      tube, the notochord and the dorsal endoderm - occupy a common region prior to
      gastrulation. This common region of origin raises the possibility that
      interactions between midline progenitor cells are important for their
      specification prior to germ layer formation. RESULTS: One of four known zebrafish
      homologues of the Drosophila melanogaster cell-cell signaling gene Delta, deltaA
      (dlA), is expressed in the developing midline, where progenitor cells of the
      ectodermal floorplate, mesodermal notochord and dorsal endoderm lie close
      together before they occupy different germ layers. We used a reverse genetic
      strategy to isolate a missense mutation of dlA, dlAdx2, which coordinately
      disrupts the development of floorplate, notochord and dorsal endoderm. The dlAdx2
      mutant embryos had reduced numbers of floorplate and hypochord cells; these cells
      lie above and beneath the notochord, respectively. In addition, mutant embryos
      had excess notochord cells. Expression of a dominant-negative form of Delta
      protein driven by mRNA microinjection produced a similar effect. In contrast,
      overexpression of dlA had the opposite effect: fewer trunk notochord cells and
      excess floorplate and hypochord cells. CONCLUSION: Our results indicate that
      Delta signaling is important for the specification of midline cells. The results
      are most consistent with the hypothesis that developmentally equivalent midline
      progenitor cells require Delta-mediated signaling prior to germ layer formation
      in order to be specified as floorplate, notochord or hypochord.

PMID- 10074452
TI  - Identification of the ras GTPase-activating protein GAP1(m) as a
      phosphatidylinositol-3,4,5-trisphosphate-binding protein in vivo.
AB  - GAP1(m) is a member of the GAP1 family of Ras GTPase-activating proteins (GAPs)
      [1]. In vitro, it has been shown to bind inositol 1, 3,4,5-tetrakisphosphate
      (IP4), the water-soluble inositol head group of the lipid second messenger
      phosphatidylinositol 3,4, 5-trisphosphate (PIP3) [2] [3]. This has led to the
      suggestion that GAP1(m) might function as a PIP3 receptor in vivo [4]. Here,
      using rat pheochromocytoma PC12 cells transiently transfected with a plasmid
      expressing a chimera of green fluorescent protein fused to GAP1(m) (GFP-GAP1(m)),
      we show that epidermal growth factor (EGF) induces a rapid (less than 60 seconds)
      recruitment of GFP-GAP1(m) from the cytosol to the plasma membrane. This
      recruitment required a functional GAP1(m) pleckstrin homology (PH) domain,
      because a specific point mutation (R629C) in the PH domain that inhibits IP4
      binding in vitro [5] totally blocked EGF-induced GAP1(m) translocation.
      Furthermore, the membrane translocation was dependent on PI 3-kinase, and the
      time course of translocation paralleled the rate by which EGF stimulates the
      generation of plasma membrane PIP3 [6]. Significantly, the PIP3-induced
      recruitment of GAP1(m) did not appear to result in any detectable enhancement in
      its basal Ras GAP activity. From these results, we conclude that GAP1(m) binds
      PIP3 in vivo, and it is recruited to the plasma membrane, but does not appear to
      be activated, following agonist stimulation of PI 3-kinase.

PMID- 10074453
TI  - FGF8 functions in the specification of the right body side of the chick.
AB  - Left-right asymmetry in vertebrate embryos is first recognisable using molecular
      markers that encode secreted proteins or transcription factors. The asymmetry
      becomes morphologically obvious in the turning of the embryo and in the
      development of the heart, the gut and other visceral organs. In the chick embryo,
      a signalling pathway for the specification of the left body side was
      demonstrated. Here, Sonic hedgehog (Shh) protein is the first asymmetric signal
      identified in the node [1] [2]. Further downstream in this pathway are the left
      specific genes nodal, lefty-1, lefty-2 and Pitx2 [1] [3] [4] [5]. On the right
      body side, a function of the activin pathway is indicated by the right-sided
      expression of cActRIIa [1] [6]. We detected that another key molecule in
      vertebrate development, fibroblast growth factor 8 (FGF8) [7] [8], is expressed
      asymmetrically on the right side of the posterior node. We demonstrate that
      transcription of FGF8 is induced by activin and the FGF8 protein inhibits the
      expression of nodal and Pitx2 and leads to expression of the chicken snail
      related gene (cSnR) [9]. Left-sided application of FGF8 randomises the direction
      of heart looping.

PMID- 10074454
TI  - Simultaneous detection of multiple green fluorescent proteins in live cells by
      fluorescence lifetime imaging microscopy.
AB  - The green fluorescent protein (GFP) has proven to be an excellent fluorescent
      marker for protein expression and localisation in living cells [1] [2] [3] [4]
      [5]. Several mutant GFPs with distinct fluorescence excitation and emission
      spectra have been engineered for intended use in multi-labelling experiments [6]
      [7] [8] [9]. Discrimination of these co-expressed GFP variants by wavelength is
      hampered, however, by a high degree of spectral overlap, low quantum efficiencies
      and extinction coefficients [10], or rapid photobleaching [6]. Using fluorescence
      lifetime imaging microscopy (FLIM) [11] [12] [13] [14] [15] [16], four GFP
      variants were shown to have distinguishable fluorescence lifetimes. Among these
      was a new variant (YFP5) with spectral characteristics reminiscent of yellow
      fluorescent protein [8] and a comparatively long fluorescence lifetime. The
      fluorescence intensities of co-expressed spectrally similar GFP variants (either
      alone or as fusion proteins) were separated using lifetime images obtained with
      FLIM at a single excitation wavelength and using a single broad band emission
      filter. Fluorescence lifetime imaging opens up an additional spectroscopic
      dimension to wavelength through which novel GFP variants can be selected to
      extend the number of protein processes that can be imaged simultaneously in
      cells.

PMID- 10074455
TI  - Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in
      testicular germ cell tumours.
AB  - Metastatic cancer in adults usually has a fatal outcome. In contrast, advanced
      testicular germ cell tumours are cured in over 80% of patients using cisplatin
      based combination chemotherapy [1]. An understanding of why these cells are
      sensitive to chemotherapeutic drugs is likely to have implications for the
      treatment of other types of cancer. Earlier measurements indicate that testis
      tumour cells are hypersensitive to cisplatin and have a low capacity to remove
      cisplatin-induced DNA damage from the genome [2] [3]. We have investigated the
      nucleotide excision repair (NER) capacity of extracts from the well-defined 833K
      and GCT27 human testis tumour cell lines. Both had a reduced ability to carry out
      the incision steps of NER in comparison with extracts from known repair
      proficient cells. Immunoblotting revealed that the testis tumour cells had normal
      amounts of most NER proteins, but low levels of the xeroderma pigmentosum group A
      protein (XPA) and the ERCC1-XPF endonuclease complex. Addition of XPA
      specifically conferred full NER capacity on the testis tumour extracts. These
      results show that a low XPA level in the testis tumour cell lines is sufficient
      to explain their poor ability to remove cisplatin adducts from DNA and might be a
      major reason for the high cisplatin sensitivity of testis tumours. Targeted
      inhibition of XPA could sensitise other types of cells and tumours to cisplatin
      and broaden the usefulness of this chemotherapeutic agent.

PMID- 10074456
TI  - Importance of the pleckstrin homology domain of dynamin in clathrin-mediated
      endocytosis.
AB  - The GTPase dynamin plays an essential role in clathrin-mediated endocytosis [1]
      [2] [3]. Substantial evidence suggests that dynamin oligomerisation around the
      necks of endocytosing vesicles and subsequent dynamin-catalysed GTP hydrolysis is
      responsible for membrane fission [4] [5]. The pleckstrin homology (PH) domain of
      dynamin has previously been shown to interact with phosphoinositides, but it has
      not been determined whether this interaction is essential for dynamin's function
      in endocytosis [6] [7] [8] [9]. In this study, we address the in vivo function of
      the PH domain of dynamin by assaying the effects of deletions and point mutations
      in this region on transferrin uptake in COS-7 fibroblasts. Overexpression of a
      dynamin construct lacking its entire PH domain potently blocked transferrin
      uptake, as did overexpression of a dynamin construct containing a mutation in the
      first variable loop of the PH domain. Structural modelling of this latter mutant
      suggested that the lysine residue at position 535 (Lys535) may be critical in the
      coordination of phosphoinositides, and indeed, the purified mutant no longer
      interacted with lipid nanotubes. Interestingly, the inhibitory phenotype of cells
      expressing this dynamin mutant was partially relieved by a second mutation in the
      carboxy-terminal proline-rich domain (PRD), one that prevents dynamin from
      binding to the Src homology 3 (SH3) domain of amphiphysin. These data demonstrate
      that dynamin's interaction with phosphoinositides through its PH domain is
      essential for endocytosis. These findings also support our hypothesis that PRD
      SH3 domain interactions are important in the recruitment of dynamin to sites of
      endocytosis.

PMID- 10074457
TI  - Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1
      mutant with a defective pleckstrin homology domain.
AB  - The dynamins are 100 kDa GTPases involved in the scission of endocytic vesicles
      from the plasma membrane [1]. Dynamin-1 is present in solution as a tetramer [2],
      and undergoes further self-assembly following its recruitment to coated pits to
      form higher-order oligomers that resemble 'collars' around the necks of nascent
      coated buds [1] [3]. GTP hydrolysis by dynamin in these collars is thought to
      accompany the 'pinching off' of endocytic vesicles [1] [4]. Dynamin contains a
      pleckstrin homology (PH) domain that binds phosphoinositides [5] [6], which in
      turn enhance both the GTPase activity [5] [7] [8] and self-assembly [9] [10] of
      dynamin. We recently showed that the dynamin PH domain binds phosphoinositides
      only when it is oligomeric [6]. Here, we demonstrate that interactions between
      the dynamin PH domain and phosphoinositides are important for dynamin function in
      vivo. Full-length dynamin-1 containing mutations that abolish phosphoinositide
      binding by its PH domain was a dominant-negative inhibitor of receptor-mediated
      endocytosis. Mutated dynamin-1 with both a defective PH domain and impaired GTP
      binding and hydrolysis also inhibited receptor-mediated endocytosis. These
      findings suggest that the role of the PH domain in dynamin function differs from
      that seen for other PH domains. We propose that high-avidity binding to
      phosphoinositide-rich regions of the membrane by the multiple PH domains in a
      dynamin oligomer is critical for dynamin's ability to complete vesicle budding.

PMID- 10074458
TI  - A MAP kinase docking site is required for phosphorylation and activation of
      p90(rsk)/MAPKAP kinase-1.
AB  - Activation of the various mitogen-activated protein (MAP) kinase pathways
      converts many different extracellular stimuli into specific cellular responses by
      inducing the phosphorylation of particular groups of substrates. One important
      determinant for substrate specificity is likely to be the amino-acid sequence
      surrounding the phosphorylation site; however, these sites overlap significantly
      between different MAP kinase family members. The idea is now emerging that
      specific docking sites for protein kinases are involved in the efficient binding
      and phosphorylation of some substrates [1] [2] [3] [4]. The MAP kinase-activated
      protein (MAPKAP) kinase p90 rsk contains two kinase domains [5]: the amino
      terminal domain (D1) is required for the phosphorylation of exogenous substrates
      whereas the carboxy-terminal domain (D2) is involved in autophosphorylation.
      Association between the extracellular signal-regulated kinase (Erk) MAP kinases
      and p90(rsk) family members has been detected in various cell types including
      Xenopus oocytes [6] [7] [8], where inactive p90(rsk) is bound to the inactive
      form of the Erk2- like MAP kinase p42(mpk1). Here, we identify a new MAP kinase
      docking site located at the carboxyl terminus of p90(rsk). This docking site was
      required for the efficient phosphorylation and activation of p90(rsk) in vitro
      and in vivo and was also both necessary and sufficient for the stable and
      specific association with p42(mpk1). The sequence of the docking site was
      conserved in other MAPKAP kinases, suggesting that it might represent a new class
      of interaction motif that facilitates efficient and specific signal transduction
      by MAP kinases.

PMID- 10074459
TI  - Potato hash.

PMID- 10074460
TI  - The olympus-current biology photomicrography competition 

PMID- 10074461
TI  - Calcium signalling.

PMID- 10074462
TI  - Mentoring: who needs it?

PMID- 10074463
TI  - Rac and Rho.

PMID- 10074464
TI  - Renin inhibition by substituted piperidines: a novel paradigm for the inhibition
      of monomeric aspartic proteinases?
AB  - BACKGROUND: The aspartic proteinase renin catalyses the first and rate-limiting
      step in the conversion of angiotensinogen to the hormone angiotensin II, and
      therefore plays an important physiological role in the regulation of blood
      pressure. Numerous potent peptidomimetic inhibitors of this important drug target
      have been developed, but none of these compounds have progressed past clinical
      phase II trials. Limited oral bioavailability or excessive production costs have
      prevented these inhibitors from becoming new antihypertensive drugs. We were
      interested in developing new nonpeptidomimetic renin inhibitors. RESULTS: High
      throughput screening of the Roche compound library identified a simple 3, 4
      disubstituted piperidine lead compound. We determined the crystal structures of
      recombinant human renin complexed with two representatives of this new class.
      Binding of these substituted piperidine derivatives is accompanied by major
      induced-fit adaptations around the enzyme's active site. CONCLUSIONS: The
      efficient optimisation of the piperidine inhibitors was facilitated by structural
      analysis of the renin active site in two renin-inhibitor complexes (some of the
      piperidine derivatives have picomolar affinities for renin). These structural
      changes provide the basis for a novel paradigm for inhibition of monomeric
      aspartic proteinases.

PMID- 10074465
TI  - A small catalytic RNA motif with Diels-Alderase activity.
AB  - BACKGROUND: The 'RNA world' hypothesis requires that RNA be able to catalyze a
      wide variety of chemical reactions. In vitro selection from combinatorial RNA
      libraries has been used to identify several catalytic activities, most of which
      have resulted in a self-modification of RNA at one of its constituents. The
      formation of carbon-carbon bonds is considered an essential prerequisite for a
      complex metabolism based on RNA. RESULTS: We describe the selection and
      characterization of new ribozymes that catalyze carbon-carbon bond formation by
      Diels-Alder reaction of a biotinylated maleimide with an RNA-tethered anthracene.
      Secondary structure analysis identified a 49-nucleotide RNA motif that
      accelerates the reaction about 20,000-fold. The motif has only 11 conserved
      nucleotides that are present in most of the selected sequences. The ribozyme
      motif is remarkably adaptable with respect to cofactor and metal-ion
      requirements. The motif was also re-engineered to give a 38-mer RNA that can act
      as a 'true' catalyst on short external substrate oligonucleotide-anthracene
      conjugates. CONCLUSIONS: We have identified a small, highly abundant RNA motif
      that can solve the complex task of forming two carbon-carbon bonds between two
      reactants in trans, a catalytic capacity useful for creating prebiotically
      relevant molecules. This is the smallest and fastest RNA catalyst for carbon
      carbon bond formation reported to date.

PMID- 10074466
TI  - Regiochemical control of monolignol radical coupling: a new paradigm for lignin
      and lignan biosynthesis.
AB  - BACKGROUND: Although the lignins and lignans, both monolignol-derived coupling
      products, account for nearly 30% of the organic carbon circulating in the
      biosphere, the biosynthetic mechanism of their formation has been poorly
      understood. The prevailing view has been that lignins and lignans are produced by
      random free-radical polymerization and coupling, respectively. This view is
      challenged, mechanistically, by the recent discovery of dirigent proteins that
      precisely determine both the regiochemical and stereoselective outcome of
      monolignol radical coupling. RESULTS: To understand further the regulation and
      control of monolignol coupling, leading to both lignan and lignin formation, we
      sought to clone the first genes encoding dirigent proteins from several species.
      The encoding genes, described here, have no sequence homology with any other
      protein of known function. When expressed in a heterologous system, the
      recombinant protein was able to confer strict regiochemical and stereochemical
      control on monolignol free-radical coupling. The expression in plants of dirigent
      proteins and proposed dirigent protein arrays in developing xylem and in other
      lignified tissues indicates roles for these proteins in both lignan formation and
      lignification. CONCLUSIONS: The first understanding of regiochemical and
      stereochemical control of monolignol coupling in lignan biosynthesis has been
      established via the participation of a new class of dirigent proteins.
      Immunological studies have also implicated the involvement of potential
      corresponding arrays of dirigent protein sites in controlling lignin biopolymer
      assembly.

PMID- 10074467
TI  - Mutational analysis of active-site residues of the enterococcal D-ala-D-Ala
      dipeptidase VanX and comparison with Escherichia coli D-ala-D-Ala ligase and D
      ala-D-Ala carboxypeptidase VanY.
AB  - BACKGROUND: Vancomycin-resistant enterococci are pathogenic bacteria that
      attenuate antibiotic sensitivity by producing peptidoglycan precursors that
      terminate in D-Ala-D-lactate rather than D-Ala-D-Ala. A key enzyme in effecting
      antibiotic resistance is the metallodipeptidase VanX, which reduces the cellular
      pool of the D-Ala-D-Ala dipeptide. RESULTS: We constructed eleven mutants, using
      the recently determined VanX structure as a basis, to investigate residue
      function. Mutating Asp142 or Ser114 showed a large effect principally on KM,
      consistent with roles in recognition of the D-Ala-D-Ala termini. The drastic
      reduction or absence of activity in the Arg71 mutants correlates with a role in
      the stabilization of an anionic tetrahedral transition state. Three residues of
      the Escherichia coli D-Ala-D-Ala ligase (Ddl), Glu15, Ser 281 and Arg255, are
      similarly conserved and have equivalent functions with respect to VanX,
      consistent with a convergent evolution of active sites to bind D-Ala-D-Ala and
      lower energy barriers for formation of the tetrahedral intermediate and
      transition states. In the N-acyl-D-Ala-D-Ala carboxypeptidase VanY, all active
      site residues are conserved (except for the two responsible for recognition of
      the dipeptide amino terminus). CONCLUSIONS: The mutagenesis results support
      structure-based functional predictions and explain why the VanX dipeptidase and
      Ddl ligase show narrow specificity for the D,D-dipeptide substrate. The results
      reveal that VanX and Ddl, two enzymes that use the same substrate but proceed in
      opposite directions driven by distinct cofactors (zinc versus ATP), evolved
      similar architectural solutions to substrate recognition and catalysis
      acceleration. VanY sequence analysis predicts an active site and mechanism of
      reaction similar to VanX.

PMID- 10074468
TI  - Molecular forceps from combinatorial libraries prevent the farnesylation of Ras
      by binding to its carboxyl terminus.
AB  - INTRODUCTION: Ras is one of the major oncogenes. In order to function properly it
      has to undergo post-translational processing at its carboxyl terminus. It has
      been shown that inhibitors of farnesyl transferase, the first enzyme in the
      processing chain, can suppress the transforming activity of oncogenic Ras.
      RESULTS: We have identified molecular forceps, branched peptidic molecules, from
      combinatorial libraries that bind to the carboxyl terminus of Ras and interfere
      with its farnesylation without inhibiting the farnesyl transferase. The active
      molecules were selected by a screening against the carboxy-terminal octapeptide
      of Ras. CONCLUSIONS: The implications of our findings are twofold. First, we
      demonstrate that it is possible to prevent enzymatic transformations by blocking
      the enzyme's access to its substrate using a synthetic small molecule to mask the
      substrate. Second, we show that it is feasible to derive molecules from
      combinatorial libraries that bind a specific epitope on a protein by selecting
      these molecules with the isolated peptide epitope.

PMID- 10074469
TI  - A hydrogen-bonding triad stabilizes the chemical transition state of a group I
      ribozyme.
AB  - BACKGROUND: The group I intron is an RNA enzyme capable of efficiently catalyzing
      phosphoryl-transfer reactions. Functional groups that stabilize the chemical
      transition state of the cleavage reaction have been identified, but they are all
      located within either the 5'-exon (P1) helix or the guanosine cofactor, which are
      the substrates of the reaction. Functional groups within the ribozyme active site
      are also expected to assist in transition-state stabilization, and their role
      must be explored to understand the chemical basis of group I intron catalysis.
      RESULTS: Using nucleotide analog interference mapping and site-specific
      functional group substitution experiments, we demonstrate that the 2'-OH at A207,
      a highly conserved nucleotide in the ribozyme active site, specifically
      stabilizes the chemical transition state by approximately 2 kcal mol-1. The A207
      2'-OH only makes its contribution when the U(-1) 2'-OH immediately adjacent to
      the scissile phosphate is present, suggesting that the 2'-OHs of A207 and U(-1)
      interact during the chemical step. CONCLUSIONS: These data support a model in
      which the 3'-oxyanion leaving group of the transesterification reaction is
      stabilized by a hydrogen-bonding triad consisting of the 2'-OH groups of U(-1)
      and A207 and the exocyclic amine of G22. Because all three nucleotides occur
      within highly conserved non-canonical base pairings, this stabilization mechanism
      is likely to occur throughout group I introns. Although this mechanism utilizes
      functional groups distinctive of RNA enzymes, it is analogous to the transition
      states of some protein enzymes that perform similar phosphoryl-transfer
      reactions.

PMID- 10074470
TI  - How Taxol stabilises microtubule structure.
AB  - The structure of tubulin shows paclitaxel (Taxol(R)) binding to a pocket in beta
      tubulin on the microtubule's inner surface, which counteracts the effects of GTP
      hydrolysis occurring on the other side of the monomer.

PMID- 10074471
TI  - Do enzymes obey the Baldwin rules? A mechanistic imperative in enzymatic
      cyclization reactions.
AB  - It is commonly assumed that enzymes have evolved to abide by the same energetic
      and stereoelectronic principles that govern reactions in solution. The principles
      formulated for organic ring-closure reactions can be used to develop a hypothesis
      for analysis of enzyme-catalyzed cyclization reactions.

PMID- 10074472
TI  - Mechanistic alternatives in phosphate monoester hydrolysis: what conclusions can
      be drawn from available experimental data?
AB  - Phosphate monoester hydrolysis reactions in enzymes and solution are often
      discussed in terms of whether the reaction pathway is associative or
      dissociative. Although experimental results for solution reactions have usually
      been considered as evidence for the second alternative, a closer thermodynamic
      analysis of observed linear free energy relationships shows that experimental
      information is consistent with the associative, concerted and dissociative
      alternatives.

PMID- 10074473
TI  - Beating the odds: a cardiomyocyte cell line at last.

PMID- 10074474
TI  - Accessory factors and the regulation of epithelial sodium channel activity.

PMID- 10074475
TI  - Immunodeficiency due to defective antigen processing: the molecular basis for
      type 1 bare lymphocyte syndrome.

PMID- 10074476
TI  - Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1).
AB  - Proliferation and apoptosis are increased in many types of inflammatory diseases.
      A role for the cyclin kinase inhibitor p27(Kip1) (p27) in limiting proliferation
      has been shown. In this study, we show that p27(-/-) mesangial cells and
      fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when
      deprived of growth factors. Apoptosis was rescued by restoration of p27
      expression. Cyclin A-cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E
      CDK2 activity, was increased in serum-starved p27(-/-) cells, and decreasing CDK2
      activity, either pharmacologically (Roscovitine) or by a dominant-negative
      mutant, inhibited apoptosis. Our results show that a new biological function for
      the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2
      activity. These results suggest that CDK inhibitors are necessary for
      coordinating the cell cycle and cell-death programs so that cell viability is
      maintained during exit from the cell cycle.

PMID- 10074477
TI  - Dynamic regulation of gastric surface pH by luminal pH.
AB  - In vivo confocal imaging of the mucosal surface of rat stomach was used to
      measure pH noninvasively under the mucus gel layer while simultaneously imaging
      mucus gel thickness and tissue architecture. When tissue was superfused at pH 3,
      the 25 microm adjacent to the epithelial surface was relatively alkaline (pH 4.1
      +/- 0.1), and surface alkalinity was enhanced by topical dimethyl prostaglandin
      E2 (pH 4.8 +/- 0.2). Luminal pH was changed from pH 3 to pH 5 to mimic the fasted
      to-fed transition in intragastric pH in rats. Under pH 5 superfusion, surface pH
      was relatively acidic (pH 4.2 +/- 0.2). This surface acidity was enhanced by
      pentagastrin (pH 3.5 +/- 0.2) and eliminated by omeprazole, implicating parietal
      cell H,K-ATPase as the dominant regulator of surface pH under pH 5 superfusion.
      With either pH 5 or pH 3 superfusion (a) gastric pit lumens had the most
      divergent pH from luminal superfusates; (b) qualitatively similar results were
      observed with and without superfusion flow; (c) local mucus gel thickness was a
      poor predictor of surface pH values; and (d) no channels carrying primary gastric
      gland fluid through the mucus were observed. The model of gastric defense that
      includes an alkaline mucus gel and viscous fingering of secreted acid through the
      mucus may be appropriate at the intragastric pH of the fasted, but not fed,
      animal.

PMID- 10074478
TI  - Minimally modified low-density lipoprotein induces monocyte adhesion to
      endothelial connecting segment-1 by activating beta1 integrin.
AB  - We have shown previously that treatment of human aortic endothelial cells (HAECs)
      with minimally modified low-density lipoprotein (MM-LDL) induces monocyte but not
      neutrophil binding. This monocyte binding was not mediated by endothelial E
      selectin, P-selectin, vascular cell adhesion molecule-I, or intercellular
      adhesion molecule-I, suggesting an alternative monocyte-specific adhesion
      molecule. We now show that moncytic alpha4beta1 integrins mediate binding to MM
      LDL-treated endothelial cells. We present data suggesting that the expression of
      the connecting segment-1 (CS-1) domain of fibronectin (FN) is induced on the
      apical surface of HAEC by MM-LDL and is the endothelial alpha4beta1 ligand in MM
      LDL-treated cells. Although the levels of CS-1 mRNA and protein were not
      increased, we show that MM-LDL treatment causes deposition of FN on the apical
      surface by activation of beta1integrins, particularly those associated with
      alpha5 integrins. Activation of beta1 by antibody 8A2 also induced CS-1-mediated
      monocyte binding. Confocal microscopy demonstrated the activated beta1 and CS
      1colocalize in concentrated filamentous patches on the apical surface of HAEC.
      Both anti-CS-1 and an antibody to activated beta1 showed increased staining on
      the luminal endothelium of human coronary lesions with active monocyte entry.
      These results suggest the importance of these integrin ligand interactions in
      human atherosclerosis.

PMID- 10074479
TI  - Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice.
AB  - Several lines of evidence show the importance of angiotensin II (AII) in renal
      injuries, especially when hemodynamic abnormalities are involved. To elucidate
      the role of AII in immune-mediated renal injury, we studied anti-glomerular
      basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient
      homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the
      renin-angiotensin system (RAS) was observed in both groups of mice at around day
      1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was
      transiently induced at six hours in both groups, which was then downregulated at
      day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of
      MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed,
      and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and
      collagen type I increased, resulting in severe glomerulosclerosis and
      interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria,
      and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this
      amelioration is likely due to the lack of AT1a, we can conclude that AII action,
      mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may
      contribute to the exacerbation of glomerular MCP-1 expression. These results
      suggest the involvement of AII in immune-mediated renal injuries.

PMID- 10074480
TI  - Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and
      alters fetal lung development in monkeys.
AB  - It is well established that maternal smoking during pregnancy is a leading
      preventable cause of low birth weight and prematurity. Less appreciated is that
      maternal smoking during pregnancy is also associated with alterations in
      pulmonary function at birth and greater incidence of respiratory illnesses after
      birth. To determine if this is the direct result of nicotine interacting with
      nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys
      were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy.
      Nicotine administration caused lung hypoplasia and reduced surface complexity of
      developing alveoli. Immunohistochemistry and in situ alpha-bungarotoxin
      (alphaBGT) binding showed that alpha7 nAChRs are present in the developing lung
      in airway epithelial cells, cells surrounding large airways and blood vessels,
      alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine
      cells (PNEC). As detected both by immunohistochemistry and by alphaBGT binding,
      nicotine administration markedly increased alpha7 receptor subunit expression and
      binding in the fetal lung. Correlating with areas of increased alpha7 expression,
      collagen expression surrounding large airways and vessels was significantly
      increased. Nicotine also significantly increased numbers of type II cells and
      neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that
      nicotine can alter fetal monkey lung development by crossing the placenta to
      interact directly with nicotinic receptors on non-neuronal cells in the
      developing lung, and that similar effects likely occur in human infants whose
      mothers smoke during pregnancy.

PMID- 10074481
TI  - P-selectin deficiency exacerbates experimental glomerulonephritis: a protective
      role for endothelial P-selectin in inflammation.
AB  - P-selectin is a leukocyte adhesion receptor present in endothelial cells and
      platelets. We examined the role of P-selectin in the autologous phase of an
      accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis
      using P-selectin-deficient mice and chimeric mice expressing P-selectin only in
      platelets or endothelial cells. P-selectin-deficient mice exhibited more severe
      glomerular damage with increased interstitial mononuclear leukocytic infiltrates,
      and had significantly increased proteinuria and mortality when compared to wild
      type mice. P-selectin on the endothelium was predominantly responsible for
      protection from the exacerbated disease, because chimeric mice with endothelial P
      selectin, and not mice with platelet P-selectin, showed glomerular injury similar
      to that in wild-type animals. Levels of soluble circulating P-selectin were
      increased in nephritic wild-type mice and in chimeric mice with endothelial P
      selectin, but not platelet P-selectin. Levels of soluble P-selectin, which has
      been shown to be anti-inflammatory in vitro, were inversely associated with the
      severity of disease. P-selectin was not expressed in the endothelium of the
      glomerulus or interstitium. Thus, the protective effect in wild-type mice may be
      accounted for, in part by soluble P-selectin shed by non-renal endothelial cells,
      although other endothelial P-selectin-dependent mechanisms cannot be ruled out.

PMID- 10074482
TI  - Altered cardiac excitation-contraction coupling in mutant mice with familial
      hypertrophic cardiomyopathy.
AB  - Excitation-contraction coupling in cardiac muscle of familial hypertrophic
      cardiomyopathy (FHC) remains poorly understood, despite the fact that the genetic
      alterations are well defined. We characterized calcium cycling and contractile
      activation in trabeculae from a mutant mouse model of FHC (Arg403Gln knockin,
      alpha-myosin heavy chain). Wild-type mice of the same strain and age (
      approximately 20 weeks old) served as controls. During twitch contractions, peak
      intracellular Ca2+ ([Ca2+]i) was higher in mutant muscles than in the wild-type
      (P < 0.05), but force development was equivalent in the two groups. Ca2+
      transient amplitude increased dramatically in both groups as stimulation rate
      increased from 0.2 to 4 Hz. Nevertheless, developed force fell at the higher
      stimulation rates in the mutants but not in controls (P < 0.05). The steady-state
      force-[Ca2+]i relationship was less steep in mutants (Hill coefficient, 2.94 +/-
      0.27 vs. 5.28 +/- 0.64; P > 0.003), with no changes in the [Ca2+]i required for
      50% activation or maximal Ca2+-activated force. Thus, calcium cycling and
      myofilament properties are both altered in FHC mutant mice: more Ca2+ is
      mobilized to generate force, but this does not suffice to maintain contractility
      at high stimulation rates.

PMID- 10074483
TI  - Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome.
AB  - Liddle's syndrome is an inherited form of hypertension linked to mutations in the
      epithelial Na+ channel (ENaC). ENaC is composed of three subunits (alpha, beta,
      gamma), each containing a COOH-terminal PY motif (xPPxY). Mutations causing
      Liddle's syndrome alter or delete the PY motifs of beta- or gamma-ENaC. We
      recently demonstrated that the ubiquitin-protein ligase Nedd4 binds these PY
      motifs and that ENaC is regulated by ubiquitination. Here, we investigate, using
      the Xenopus oocyte system, whether Nedd4 affects ENaC function. Overexpression of
      wild-type Nedd4, together with ENaC, inhibited channel activity, whereas a
      catalytically inactive Nedd4 stimulated it, likely by acting as a competitive
      antagonist to endogenous Nedd4. These effects were dependant on the PY motifs,
      because no Nedd4-mediated changes in channel activity were observed in ENaC
      lacking them. The effect of Nedd4 on ENaC missing only one PY motif (of beta
      ENaC), as originally described in patients with Liddle's syndrome, was
      intermediate. Changes were due entirely to alterations in ENaC numbers at the
      plasma membrane, as determined by surface binding and immunofluorescence. Our
      results demonstrate that Nedd4 is a negative regulator of ENaC and suggest that
      the loss of Nedd4 binding sites in ENaC observed in Liddle's syndrome may explain
      the increase in channel number at the cell surface, increased Na+ reabsorption by
      the distal nephron, and hence the hypertension.

PMID- 10074484
TI  - Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in
      patients with hypokalemic periodic paralysis.
AB  - The adenosine triphosphate (ATP)-sensitive K+ (KATP) channel is the most abundant
      K+ channel active in the skeletal muscle fibers of humans and animals. In the
      present work, we demonstrate the involvement of the muscular KATP channel in a
      skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is
      caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle
      biopsies excised from three patients with HOPP carrying the R528H mutation of the
      dihydropyridine receptor showed a reduced sarcolemma KATP current that was not
      stimulated by magnesium adenosine diphosphate (MgADP; 50-100 microM) and was
      partially restored by cromakalim. In contrast, large KATP currents stimulated by
      MgADP were recorded in the healthy subjects. At channel level, an abnormal KATP
      channel showing several subconductance states was detected in the patients with
      HOPP. None of these were surveyed in the healthy subjects. Transitions of the
      KATP channel between subconductance states were also observed after in vitro
      incubation of the rat muscle with low-K+ solution. The lack of the sarcolemma
      KATP current observed in these patients explains the symptoms of the disease,
      i.e., hypokalemia, depolarization of the fibers, and possibly the paralysis
      following insulin administration.

PMID- 10074485
TI  - Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2.
AB  - Deficiency of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in humans
      leads to the syndrome of apparent mineralocorticoid excess (SAME), in which
      cortisol illicitly occupies mineralocorticoid receptors, causing sodium
      retention, hypokalemia, and hypertension. However, the disorder is usually
      incompletely corrected by suppression of cortisol, suggesting additional and
      irreversible changes, perhaps in the kidney. To examine this further, we produced
      mice with targeted disruption of the 11beta-HSD2 gene. Homozygous mutant mice
      (11beta-HSD2(-/-)) appear normal at birth, but approximately 50% show motor
      weakness and die within 48 hours. Both male and female survivors are fertile but
      exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity
      of corticosterone. Young adult 11beta-HSD2(-/-) mice are markedly hypertensive,
      with a mean arterial blood pressure of 146 +/- 2 mmHg, compared with 121 +/- 2
      mmHg in wild-type controls and 114 +/- 4 mmHg in heterozygotes. The epithelium of
      the distal tubule of the nephron shows striking hypertrophy and hyperplasia.
      These histological changes do not readily reverse with mineralocorticoid receptor
      antagonism in adulthood. Thus, 11beta-HSD2(-/-) mice demonstrate the major
      features of SAME, providing a unique rodent model to study the molecular
      mechanisms of kidney resetting leading to hypertension.

PMID- 10074486
TI  - Impaired physiological responses to chronic hypoxia in mice partially deficient
      for hypoxia-inducible factor 1alpha.
AB  - Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular
      hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates
      transcription of genes encoding proteins that mediate adaptive responses to
      hypoxia, including erythropoietin, vascular endothelial growth factor, and
      glycolytic enzymes. Expression of the HIF-1alpha subunit increases exponentially
      as O2 concentration is decreased. Hif1a-/- mouse embryos with complete deficiency
      of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus die at
      midgestation, with multiple cardiovascular malformations and mesenchymal cell
      death. Hif1a+/- heterozygotes develop normally and are indistinguishable from
      Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this
      study, the physiological responses of Hif1a+/- and Hif1a+/+ mice exposed to 10%
      O2 for one to six weeks were analyzed. Hif1a+/- mice demonstrated significantly
      delayed development of polycythemia, right ventricular hypertrophy, pulmonary
      hypertension, and pulmonary vascular remodeling and significantly greater weight
      loss compared with wild-type littermates. These results indicate that partial HIF
      1alpha deficiency has significant effects on multiple systemic responses to
      chronic hypoxia.

PMID- 10074487
TI  - Cardiomyocytes can be generated from marrow stromal cells in vitro.
AB  - We have isolated a cardiomyogenic cell line (CMG) from murine bone marrow stromal
      cells. Stromal cells were immortalized, treated with 5-azacytidine, and
      spontaneously beating cells were repeatedly screened. The cells showed a
      fibroblast-like morphology, but the morphology changed after 5-azacytidine
      treatment in approximately 30% of the cells; they connected with adjoining cells
      after one week, formed myotube-like structures, began spontaneously beating after
      two weeks, and beat synchronously after three weeks. They expressed atrial
      natriuretic peptide and brain natriuretic peptide and were stained with anti
      myosin, anti-desmin, and anti-actinin antibodies. Electron microscopy revealed a
      cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally
      positioned nucleus, and atrial granules. These cells had several types of action
      potentials, such as sinus node-like and ventricular cell-like action potentials.
      All cells had a long action potential duration or plateau, a relatively shallow
      resting membrane potential, and a pacemaker-like late diastolic slow
      depolarization. Analysis of the isoform of contractile protein genes, such as
      myosin heavy chain, myosin light chain, and alpha-actin, indicated that their
      muscle phenotype was similar to that of fetal ventricular cardiomyocytes. These
      cells expressed Nkx2.5/Csx, GATA4, TEF-1, and MEF-2C mRNA before 5-azacytidine
      treatment and expressed MEF-2A and MEF-2D after treatment. This new cell line
      provides a powerful model for the study of cardiomyocyte differentiation.

PMID- 10074488
TI  - Maleic acid and succinic acid in fermented alcoholic beverages are the stimulants
      of gastric acid secretion.
AB  - Alcoholic beverages produced by fermentation (e.g., beer and wine) are powerful
      stimulants of gastric acid output and gastrin release in humans. The aim of this
      study was to separate and specify the gastric acid stimulatory ingredients in
      alcoholic beverages produced by fermentation. Yeast-fermented glucose was used as
      a simple model of fermented alcoholic beverages; it was stepwise separated by
      different methods of liquid chromatography, and each separated solution was
      tested in human volunteers for its stimulatory action on gastric acid output and
      gastrin release. Five substances were detected by high-performance liquid
      chromatography and were analyzed by mass spectrometry and 1H-13C nuclear magnetic
      resonance spectroscopy. At the end of the separation process of the five
      identified substances, only the two dicarboxylic acids, maleic acid and succinic
      acid, had a significant (P < 0.05) stimulatory action on gastric acid output (76%
      and 70% of fermented glucose, respectively), but not on gastrin release. When
      given together, they increased gastric acid output by 100% of fermented glucose
      and by 95% of maximal acid output. We therefore conclude that maleic acid and
      succinic acid are the powerful stimulants of gastric acid output in fermented
      glucose and alcoholic beverages produced by fermentation, and that gastrin is not
      their mediator of action.

PMID- 10074489
TI  - Cell-wall determinants of the bactericidal action of group IIA phospholipase A2
      against Gram-positive bacteria.
AB  - We have shown previously that a group IIA phospholipase A2 (PLA2) is responsible
      for the potent bactericidal activity of inflammatory fluids against many Gram
      positive bacteria. To exert its antibacterial activity, this PLA2 must first bind
      and traverse the bacterial cell wall to produce the extensive degradation of
      membrane phospholipids (PL) required for bacterial killing. In this study, we
      have examined the properties of the cell-wall that may determine the potency of
      group IIA PLA2 action. Inhibition of bacterial growth by nutrient deprivation or
      a bacteriostatic antibiotic reversibly increased bacterial resistance to PLA2
      triggered PL degradation and killing. Conversely, pretreatment of Staphylococcus
      aureus or Enterococcus faecium with subinhibitory doses of beta-lactam
      antibiotics increased the rate and extent of PL degradation and/or bacterial
      killing after addition of PLA2. Isogenic wild-type (lyt+) and autolysis-deficient
      (lyt-) strains of S. aureus were equally sensitive to the phospholipolytic action
      of PLA2, but killing and lysis was much greater in the lyt+ strain. Thus, changes
      in cell-wall cross-linking and/or autolytic activity can modulate PLA2 action
      either by affecting enzyme access to membrane PL or by the coupling of massive PL
      degradation to autolysin-dependent killing and bacterial lysis or both. Taken
      together, these findings suggest that the bacterial envelope sites engaged in
      cell growth may represent preferential sites for the action and cytotoxic
      consequences of group IIA PLA2 attack against Gram-positive bacteria.

PMID- 10074490
TI  - Defective high-affinity thiamine transporter leads to cell death in thiamine
      responsive megaloblastic anemia syndrome fibroblasts.
AB  - We have investigated the cellular pathology of the syndrome called thiamine
      responsive megaloblastic anemia (TRMA) with diabetes and deafness. Cultured
      diploid fibroblasts were grown in thiamine-free medium and dialyzed serum. Normal
      fibroblasts survived indefinitely without supplemental thiamine, whereas patient
      cells died in 5-14 days (mean 9.5 days), and heterozygous cells survived for more
      than 30 days. TRMA fibroblasts were rescued from death with 10-30 nM thiamine (in
      the range of normal plasma thiamine concentrations). Positive terminal
      deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining
      suggested that cell death was due to apoptosis. We assessed cellular uptake of
      [3H]thiamine at submicromolar concentrations. Normal fibroblasts exhibited
      saturable, high-affinity thiamine uptake (Km 400-550 nM; Vmax 11 pmol/min/10(6)
      cells) in addition to a low-affinity unsaturable component. Mutant cells lacked
      detectable high-affinity uptake. At 30 nM thiamine, the rate of uptake of
      thiamine by TRMA fibroblasts was 10-fold less than that of wild-type, and cells
      from obligate heterozygotes had an intermediate phenotype. Transfection of TRMA
      fibroblasts with the yeast thiamine transporter gene THI10 prevented cell death
      when cells were grown in the absence of supplemental thiamine. We therefore
      propose that the primary abnormality in TRMA is absence of a high-affinity
      thiamine transporter and that low intracellular thiamine concentrations in the
      mutant cells cause biochemical abnormalities that lead to apoptotic cell death.

PMID- 10074491
TI  - Characterization of novel cathepsin K mutations in the pro and mature polypeptide
      regions causing pycnodysostosis.
AB  - Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by
      osteoclasts, was recently identified as the deficient enzyme causing
      pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To
      investigate the nature of molecular lesions causing this disease, mutations in
      the cathepsin K gene from eight families were determined, identifying seven novel
      mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the
      first pro region missense mutation in a cysteine protease, G79E, in Pichia
      pastoris resulted in an unstable precursor protein, consistent with misfolding of
      the proenzyme. Expression of five mature region missense defects revealed that
      G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins
      or protease activity were detected. The Y212C precursor was activated to its
      mature form in a manner similar to that of the wild-type cathepsin K. The mature
      Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic
      activity, but it had markedly decreased activity toward type I collagen and a
      cathepsin K-specific tripeptide substrate, indicating that it was unable to bind
      collagen triple helix. These studies demonstrated the molecular heterogeneity of
      mutations causing pycnodysostosis, indicated that pro region conformation directs
      proper folding of the proenzyme, and suggested that the cathepsin K active site
      contains a critical collagen-binding domain.

PMID- 10074492
TI  - Preservation of canine myocardial high-energy phosphates during low-flow ischemia
      with modification of hemoglobin-oxygen affinity.
AB  - Conventional approaches for the treatment of myocardial ischemia increase
      coronary blood flow or reduce myocardial demand. To determine whether a rightward
      shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and
      contractile effects of a myocardial oxygen-supply imbalance, we studied the
      impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a
      2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic
      acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high
      energy phosphate levels and pH were studied by 31P nuclear magnetic resonance
      (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle
      control during a reversible reduction of left anterior descending (LAD) coronary
      artery blood flow. Changes in cardiac metabolites and regional ventricular
      function studied by pressure segment-length relations were also investigated in
      additional animals before and after RSR13 administration during low-flow LAD
      ischemia. The intravenous administration of RSR13 before ischemia resulted in a
      substantial increase in the mean hemoglobin p50 and attenuated the decline in
      cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH
      during ischemia without a change in regional myocardial blood flow, heart rate,
      or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also
      improved cardiac PCr/ATP ratios and regional function as measured by fractional
      shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin
      oxygen affinity may be a new and important therapeutic strategy to ameliorate the
      metabolic and functional consequences of cardiac ischemia.

PMID- 10074493
TI  - The atherogenic effects of chlamydia are dependent on serum cholesterol and
      specific to Chlamydia pneumoniae.
AB  - Epidemiological investigations have linked Chlamydia pneumoniae infection to
      atherosclerosis. It is not clear, however, whether C. pneumoniae infection plays
      a causal role in the development of atherosclerosis. Mice with low-density
      lipoprotein receptor deficiency were induced to develop atherosclerotic lesions
      in aorta with a cholesterol-enriched diet that increased serum cholesterol by two
      to threefold. Using this mouse model, we found that the chlamydial infection
      alone with either the C. pneumoniae AR39 or the C. trachomatis MoPn strain failed
      to induce any significant atherosclerotic lesions in aorta over a period of nine
      months. However, in the presence of a high-cholesterol diet, infection with the
      C. pneumoniae AR39 strain significantly exacerbated the hypercholesterolemia
      induced atherosclerosis, demonstrating that a hypercholesterolemic condition is
      required for the C. pneumoniae to aggravate the development of atherosclerosis.
      Although both AR39 and MoPn antigens were detected in aorta of mice infected with
      the corresponding strains, only mice infected with the C. pneumoniae strain AR39
      displayed enhanced atherosclerotic lesions, suggesting that the C. pneumoniae
      species may possess a unique atherogenic property. This study may provide a model
      for further understanding the mechanisms of C. pneumoniae atherogenesis and
      evaluating chlamydial intervention strategies for preventing the advancement of
      atherosclerotic lesions enhanced by C. pneumoniae infection.

PMID- 10074494
TI  - Splice acceptor site mutation of the transporter associated with antigen
      processing-1 gene in human bare lymphocyte syndrome.
AB  - Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the
      cell surface depends on the heterodimer of the transporter associated with
      antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by
      proteasome to the class I molecules. Defects in the TAP2 protein have been
      reported in two families with HLA class I deficiency, the so-called bare
      lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the
      first time a splice site mutation in the TAP1 gene of another BLS patient. In
      addition, class I heavy chains (HCs) did not form the normal complex with tapasin
      in the endoplasmic reticulum (ER) of the cells of our patient.

PMID- 10074495
TI  - HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter
      TAP1.
AB  - The transporter associated with antigen processing (TAP), which is composed of
      two subunits (TAP1 and TAP2) that have different biochemical and functional
      properties, plays a key role in peptide loading and the cell surface expression
      of HLA class I molecules. Three cases of HLA class I deficiency have previously
      been shown to result from the absence of a functional TAP2 subunit. In the
      present study, we analyzed two cases displaying not only the typical lung
      syndrome of HLA class I deficiency but also skin lesions, and found these
      patients to be TAP1-deficient. This defect leads to unstable HLA class I
      molecules and their retention in the endoplasmic reticulum. However, the absence
      of TAP1 is compatible with life and does not seem to result in higher
      susceptibility to viral infections than TAP2 deficiency. This work also reveals
      that vasculitis is often observed in HLA class I-deficient patients.

PMID- 10074496
TI  - Controversies affecting the future practice of clinical microbiology.

PMID- 10074497
TI  - Isolation of Lyme disease Borrelia from puffins (Fratercula arctica) and seabird
      ticks (Ixodes uriae) on the Faeroe Islands.
AB  - This is the first report on the isolation of Lyme disease Borrelia from seabirds
      on the Faeroe Islands and the characteristics of its enzootic cycle. The major
      components of the Borrelia cycle include the puffin (Fratercula arctica) as the
      reservoir and Ixodes uriae as the vector. The importance of this cycle and its
      impact on the spread of human Lyme borreliosis have not yet been established.
      Borrelia spirochetes isolated from 2 of 102 sampled puffins were compared to the
      borreliae previously obtained from seabird ticks, I. uriae. The rrf-rrl
      intergenic spacer and the rrs and the ospC genes were sequenced and a series of
      phylogenetic trees were constructed. Sequence data and restriction fragment
      length polymorphism analysis grouped the strains together with Borrelia garinii.
      In a seroepidemiological survey performed with residents involved in puffin
      hunting on the Faeroe Islands, 3 of 81 serum samples were found to be positive by
      two commonly used clinical tests: a flagellin-based enzyme-linked immunosorbent
      assay (ELISA) and Western blotting. These three positive serum samples also had
      high optical density values in a whole-cell ELISA. The finding of seropositive
      Faeroe Islanders who are regularly exposed to I. uriae indicate that there may be
      a transfer of B. garinii by this tick species to humans.

PMID- 10074498
TI  - Extremely high incidence of macrolide and trimethoprim-sulfamethoxazole
      resistance among clinical isolates of Streptococcus pneumoniae in Taiwan.
AB  - From January 1996 to December 1997, 200 isolates of Streptococcus pneumoniae
      recovered from 200 patients treated at National Taiwan University Hospital were
      serotyped and their susceptibilities to 16 antimicrobial agents were determined
      by the agar dilution method. Sixty-one percent of the isolates were
      nonsusceptible to penicillin, exhibiting either intermediate resistance (28%) or
      high-level resistance (33%). About two-fifths of the isolates displayed
      intermediate or high-level resistance to cefotaxime, ceftriaxone, cefepime,
      imipenem, and meropenem. Extremely high proportions of the isolates were
      resistant to erythromycin (82%), clarithromycin (90%), and trimethoprim
      sulfamethoxazole (TMP-SMZ) (87%). Among the isolates nonsusceptible to
      penicillin, 23.8% were resistant to imipenem; more than 60% displayed resistance
      to cefotaxime, ceftriaxone, cefepime, and carbapenems; 96.7% were resistant to
      erythromycin; and 100% were resistant to TMP-SMZ. All isolates were susceptible
      to rifampin and vancomycin. The MICs at which 50% and 90% of the isolates were
      inhibited were 0.12 and 1 microgram/ml, respectively, for cefpirome, and 0.12 and
      0.25 microgram/ml, respectively, for moxifloxacin. Six serogroups or serotypes
      (23F, 19F, 6B, 14, 3, and 9) accounted for 77.5% of all isolates. Overall, 92.5%
      of the isolates were included in the serogroups or serotypes represented in the
      23-valent pneumococcal vaccine. The incidence of macrolide and TMP-SMZ resistance
      for S. pneumoniae isolates in Taiwan in this study is among the highest in the
      world published to date.

PMID- 10074499
TI  - Clinical significance of expression of human cytomegalovirus pp67 late transcript
      in heart, lung, and bone marrow transplant recipients as determined by nucleic
      acid sequence-based amplification.
AB  - Human cytomegalovirus (HCMV) infection was monitored retrospectively by
      qualitative determination of pp67 mRNA (a late viral transcript) by nucleic acid
      sequence-based amplification (NASBA) in a series of 50 transplant recipients,
      including 26 solid-organ (11 heart and 15 lung) transplant recipients (SOTRs) and
      24 bone marrow transplant recipients (BMTRs). NASBA results were compared with
      those obtained by prospective quantitation of HCMV viremia and antigenemia and
      retrospective quantitation of DNA in leukocytes (leukoDNAemia). On the whole, 29
      patients were NASBA positive, whereas 10 were NASBA negative, and the blood of 11
      patients remained HCMV negative. NASBA detected HCMV infection before
      quantitation of viremia did but after quantitation of leukoDNAemia and
      antigenemia did. In NASBA-positive blood samples, median levels of viremia,
      antigenemia, and leukoDNAemia were significantly higher than the relevant levels
      detected in NASBA-negative HCMV-positive blood samples. By using the quantitation
      of leukoDNAemia as the "gold standard," the analytical sensitivity (47.3%), as
      well as the negative predictive value (68. 3%), of NASBA for the diagnosis of
      HCMV infection intermediate between that of antigenemia quantitation (analytical
      sensitivity, 72. 3%) and that of viremia quantitation (analytical sensitivity,
      28.7%), while the specificity and the positive predictive value were high (90 to
      100%). However, with respect to the clinically relevant antigenemia cutoff of
      >/=100 used in this study for the initiation of preemptive therapy in SOTRs with
      reactivated HCMV infection, the clinical sensitivity of NASBA reached 100%, with
      a specificity of 68. 9%. Upon the initiation of antigenemia quantitation-guided
      treatment, the actual median antigenemia level was 158 (range, 124 to 580) in
      SOTRs who had reactivated infection and who presented with NASBA positivity 3.5
      +/- 2.6 days in advance and 13.5 (range, 1 to 270) in the group that included
      BMTRs and SOTRs who had primary infection (in whom treatment was initiated upon
      the first confirmation of detection of HCMV in blood) and who presented with
      NASBA positivity 2.0 +/- 5.1 days later. Following antiviral treatment, the
      durations of the presence of antigenemia and pp67 mRNA in blood were found to be
      similar. In conclusion, monitoring of the expression of HCMV pp67 mRNA appears to
      be a promising, well-standardized tool for determination of the need for the
      initiation and termination of preemptive therapy. Its overall clinical impact
      should be analyzed in future prospective studies.

PMID- 10074500
TI  - PCR-based restriction pattern typing of the vacA gene provides evidence for a
      homogeneous group among Helicobacter pylori strains associated with peptic ulcer
      disease.
AB  - The results of PCR-based molecular typing of Helicobacter pylori strains by
      restriction fragment length polymorphism analysis of a 1, 161-bp nucleotide
      sequence of the midregion of the vacA gene are reported. A total of 48 H. pylori
      strains isolated from gastric biopsy specimens obtained from 18 patients with
      peptic ulcer dyspepsia, 15 patients with nonulcer dyspepsia, and 15 asymptomatic
      H. pylori-infected subjects were studied. Highly heterogeneous restriction
      patterns were obtained by digestion of PCR products with SauII, BglII, and HhaI,
      whereas HaeIII digestion resulted in a strictly homogeneous profile for H. pylori
      strains isolated from 14 of 18 (77.7%) patients with peptic ulcer dyspepsia, but
      a strictly homogeneous profile was found for strains from only 8 of 15 (53.3%)
      patients with nonulcer dyspepsia (P = 0.163) and 5 of 15 (33.3%) asymptomatic H.
      pylori-infected subjects (P = 0.014). A potentially important aspect of the
      results obtained is the clinical relevance, since a single restriction pattern
      seems to be able to identify the majority of H. pylori strains associated with
      peptic ulcer disease.

PMID- 10074501
TI  - Extensive cross-contamination of specimens with Mycobacterium tuberculosis in a
      reference laboratory.
AB  - A striking increase in the numbers of cultures positive for Mycobacterium
      tuberculosis was noticed in a mycobacterial reference laboratory in Campinas, Sao
      Paulo State, Brazil, in May 1995. A contaminated bronchoscope was the suspected
      cause of the increase. All 91 M. tuberculosis isolates grown from samples from
      patients between 8 May and 18 July 1995 were characterized by spoligotyping and
      IS6110 fingerprinting. Sixty-one of the 91 isolates had identical spoligotype
      patterns, and the pattern was arbitrarily designated S36. The 61 specimens
      containing these isolates had been processed and cultured in a 21-day period
      ending on 1 June 1995, but only 1 sample was smear positive for acid-fast
      bacilli. The patient from whom this sample was obtained was considered to be the
      index case patient and had a 4+ smear-positive lymph node aspirate that had been
      sent to the laboratory on 10 May. Virtually all organisms with spoligotype S36
      had the same IS6110 fingerprint pattern. Extensive review of the patients' charts
      and investigation of laboratory procedures revealed that cross-contamination of
      specimens had occurred. Because the same strain was grown from all types of
      specimens, the bronchoscope was ruled out as the outbreak source. The most likely
      source of contamination was a multiple-use reagent used for specimen processing.
      The organism was cultured from two of the solutions 3 weeks after mock
      contamination. This investigation strongly supports the idea that M. tuberculosis
      grown from smear-negative specimens should be analyzed by rapid and reliable
      strain differentiation techniques, such as spoligotyping, to help rule out
      laboratory contamination.

PMID- 10074502
TI  - Phylogenetic classification and species identification of dermatophyte strains
      based on DNA sequences of nuclear ribosomal internal transcribed spacer 1
      regions.
AB  - The mutual phylogenetic relationships of dermatophytes of the genera
      Trichophyton, Microsporum, and Epidermophyton were demonstrated by using internal
      transcribed spacer 1 (ITS1) region ribosomal DNA sequences. Trichophyton spp. and
      Microsporum spp. form a cluster in the phylogenetic tree with Epidermophyton
      floccosum as an outgroup, and within this cluster, all Trichophyton spp. except
      Trichophyton terrestre form a nested cluster (100% bootstrap support). Members of
      dermatophytes in the cluster of Trichophyton spp. were classified into three
      groups with ITS1 homologies, with each of them being a monophyletic cluster (100%
      bootstrap support). The Arthroderma vanbreuseghemii-Arthroderma simii group
      consists of A. vanbreuseghemii, A. simii, Trichophyton mentagrophytes isolates
      from humans, T. mentagrophytes var. quinckeanum, Trichophyton tonsurans, and
      Trichophyton schoenleinii. Arthroderma benhamiae, T. mentagrophytes var.
      erinacei, and Trichophyton verrucosum are members of the Arthroderma benhamiae
      group. Trichophyton rubrum and Trichophyton violaceum form the T. rubrum group.
      This suggests that these "species" of dermatophytes have been overclassified. The
      ITS1 sequences of 11 clinical isolates were also determined to identify the
      species, and all strains were successfully identified by comparison of their base
      sequences with those in the ITS1 DNA sequence database.

PMID- 10074503
TI  - Serum is more suitable than whole blood for diagnosis of systemic candidiasis by
      nested PCR.
AB  - PCR assays for the diagnosis of systemic candidiasis can be performed either on
      serum or on whole blood, but results obtained with the two kinds of samples have
      never been formally compared. Thus we designed a nested PCR assay in which five
      specific inner pairs of primers were used to amplify specific targets on the rRNA
      genes of Candida albicans, C. tropicalis, C. parapsilosis, C. krusei, and C.
      glabrata. In vitro, the lower limit of detection of each nested PCR assay was 1
      fg of purified DNA from the corresponding Candida species. In rabbits with
      candidemia of 120 minutes' duration following intravenous (i.v.) injection of
      10(8) CFU of C. albicans, the sensitivities of the PCR in serum and whole blood
      were not significantly different (93 versus 86%). In other rabbits, injected with
      only 10(5) CFU of C. albicans, detection of candidemia by culture was possible
      for only 1 min, whereas DNA could be detected by PCR in whole blood and in serum
      for 15 and 150 min, respectively. PCR was more often positive in serum than in
      whole blood in 40 culture-negative samples (27 versus 7%; P < 0.05%). Lastly,
      experiments with rabbits injected i.v. with 20 or 200 microgram of purified C.
      albicans DNA showed that PCRs were positive in serum from 30 to at least 120 min
      after injection, suggesting that the clearance of free DNA is slow. These results
      suggest that serum is the sample of choice, which should be used preferentially
      over whole blood for the diagnosis of systemic candidiasis by PCR.

PMID- 10074504
TI  - Species identification and strain differentiation of dermatophyte fungi by
      analysis of ribosomal-DNA intergenic spacer regions.
AB  - Restriction fragment length polymorphisms (RFLPs) identified in the ribosomal-DNA
      (rDNA) repeat were used for molecular strain differentiation of the dermatophyte
      fungus Trichophyton rubrum. The polymorphisms were detected by hybridization of
      EcoRI-digested T. rubrum genomic DNAs with a probe amplified from the small
      subunit (18S) rDNA and adjacent internal transcribed spacer (ITS) regions. The
      rDNA RFLPs mapped to the nontranscribed spacer (NTS) region of the rDNA repeat
      and appeared similar to those caused by short repetitive sequences in the
      intergenic spacers of other fungi. Fourteen individual RFLP patterns (DNA types A
      to N) were recognized among 50 random clinical isolates of T. rubrum. A majority
      of strains (19 of 50 [38%]) were characterized by one RFLP pattern (DNA type A),
      and four types (DNA types A to D) accounted for 78% (39 of 50) of all strains.
      The remaining types (DNA types E to N) were represented by one or two isolates
      only. A rapid and simple method was also developed for molecular species
      identification of dermatophyte fungi. The contiguous ITS and 5.8S rDNA regions
      were amplified from 17 common dermatophyte species by using the universal primers
      ITS 1 and ITS 4. Digestion of the amplified ITS products with the restriction
      endonuclease MvaI produced unique and easily identifiable fragment patterns for a
      majority of species. However, some closely related taxon pairs, such as T. rubrum
      T. soudanense and T. quinkeanum-T. schoenlenii could not be distinguished. We
      conclude that RFLP analysis of the NTS and ITS intergenic regions of the rDNA
      repeat is a valuable technique both for molecular strain differentiation of T.
      rubrum and for species identification of common dermatophyte fungi.

PMID- 10074505
TI  - Detection of antibody to avian influenza A (H5N1) virus in human serum by using a
      combination of serologic assays.
AB  - From May to December 1997, 18 cases of mild to severe respiratory illness caused
      by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence
      of an avian virus in the human population prompted an epidemiological
      investigation to determine the extent of human-to-human transmission of the virus
      and risk factors associated with infection. The hemagglutination inhibition (HI)
      assay, the standard method for serologic detection of influenza virus infection
      in humans, has been shown to be less sensitive for the detection of antibodies
      induced by avian influenza viruses. Therefore, we developed a more sensitive
      microneutralization assay to detect antibodies to avian influenza in humans.
      Direct comparison of an HI assay and the microneutralization assay demonstrated
      that the latter was substantially more sensitive in detecting human antibodies to
      H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked
      immunosorbent assay (ELISA) was also established to test children's sera. The
      sensitivity and specificity of the microneutralization assay were compared with
      those of an H5-specific indirect ELISA. When combined with a confirmatory H5
      specific Western blot test, the specificities of both assays were improved.
      Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5
      antibody in adults aged 18 to 59 years were achieved by using the
      microneutralization assay combined with Western blotting. Maximum sensitivity
      (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from
      children less than 15 years of age were achieved by using ELISA combined with
      Western blotting. This new test algorithm is being used for the seroepidemiologic
      investigations of the avian H5N1 influenza outbreak.

PMID- 10074506
TI  - Evaluation of accuracy and repeatability of identification of food-borne
      pathogens by automated bacterial identification systems.
AB  - The performances of five automated microbial identification systems, relative to
      that of a reference identification system, for their ability to accurately and
      repeatedly identify six common food-borne pathogens were assessed. The systems
      assessed were the MicroLog system (Biolog Inc., Hayward, Calif.), the Microbial
      Identification System (MIS; MIDI Inc., Newark, Del.), the VITEK system
      (bioMerieux Vitek, Hazelwood, Mo.), the MicroScan WalkAway 40 system (Dade
      MicroScan International, West Sacramento, Calif.), and the Replianalyzer system
      (Oxoid Inc., Nepean, Ontario, Canada). The sensitivities and specificities of
      these systems for the identification of food-borne isolates of Bacillus cereus,
      Campylobacter jejuni, Listeria monocytogenes, Staphylococcus aureus, Salmonella
      spp., and verotoxigenic Escherichia coli were determined with 40 reference
      positive isolates and 40 reference negative isolates for each pathogen. The
      sensitivities of these systems for the identification of these pathogens ranged
      from 42.5 to 100%, and the specificities of these systems for the identification
      of these pathogens ranged from 32.5 to 100%. Some of the systems had difficulty
      correctly identifying the reference isolates when the results were compared to
      those from the reference identification tests. The sensitivity of MIS for the
      identification of S. aureus, B. cereus, E. coli, and C. jejuni, for example,
      ranged from 47.5 to 72. 5%. The sensitivity of the Microlog system for the
      identification of E. coli was 72.5%, and the sensitivity of the VITEK system for
      the identification of B. cereus was 42.5%. The specificities of four of the five
      systems for the identification of all of the species tested with the available
      databases were greater than or equal to 97.5%; the exception was MIS for the
      identification of C. jejuni, which displayed a specificity of 32.5% when it was
      tested with reference negative isolates including Campylobacter coli and other
      Campylobacter species. All systems had >80% sensitivities for the identification
      of Salmonella species and Listeria species at the genus level. The repeatability
      of these systems for the identification of test isolates ranged from 30 to 100%.
      Not all systems included all six pathogens in their databases; thus, some species
      could not be tested with all systems. The choice of automated microbial
      identification system for the identification of a food-borne pathogen would
      depend on the availability of identification libraries within the systems and the
      performance of the systems for the identification of the pathogen.

PMID- 10074507
TI  - Amplification of the six major human herpesviruses from cerebrospinal fluid by a
      single PCR.
AB  - We used a novel type of primer system, a system that uses stair primers, in which
      the primer sequences are based on consensus sequences in the DNA polymerase gene
      of herpesvirus to detect herpesviruses by PCR. A single PCR in a single tube
      detected the six major herpesviruses that infect the central nervous system:
      herpes simplex virus type 1 (HSV-1), and type 2 (HSV-2), cytomegalovirus (CMV),
      Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and human herpesvirus 6
      (HHV-6). We used the technique to analyze 142 cerebrospinal fluid (CSF) samples
      that had been stored at -80 degrees C and compared the results with those
      obtained previously for the same samples by standard, targeted PCR. Four hundred
      one targeted PCR tests had been run with the 142 samples to detect HSV-1, HSV-2,
      CMV, and VZV; screening for EBV and HHV-6 was not prescribed when the samples
      were initially taken. Eighteen CSF samples tested positive by classic targeted
      PCR. The herpesvirus consensus PCR detected herpesviruses in 37 samples,
      including 3 samples with coinfections and 17 viral isolates which were not
      targeted. Two samples identified as infected by the targeted PCR tested negative
      by the consensus PCR, and eight samples that tested positive by the consensus PCR
      were negative by the targeted PCR. One hundred three samples scored negative by
      both the targeted and the consensus PCRs. This preliminary study demonstrates the
      value of testing for six different herpesviruses simultaneously by a sensitive
      and straightforward technique rather than screening only for those viruses that
      are causing infections as suggested by clinical signs.

PMID- 10074508
TI  - Identification of nonlipophilic corynebacteria isolated from dairy cows with
      mastitis.
AB  - Nonlipophilic corynebacteria associated with clinical and subclinical mastitis in
      dairy cows were found to belong to four species: Corynebacterium amycolatum,
      Corynebacterium ulcerans, Corynebacterium pseudotuberculosis, and Corynebacterium
      minutissimum. These species may easily be confused. However, clear-cut
      differences between C. ulcerans and C. pseudotuberculosis were found in their
      acid production from maltotriose and ethylene glycol, susceptibility to
      vibriostatic agent O129, and alkaline phosphatase. Absence of growth at 20
      degrees C and lack of alpha-glucosidase and 4MU-alpha-D-glycoside hydrolysis
      activity differentiated C. amycolatum from C. pseudotuberculosis and C. ulcerans.
      The mastitis C. pseudotuberculosis strains differed from the biovar equi and ovis
      reference strains and from caprine field strains in their colony morphologies and
      in their reduced inhibitory activity on staphylococcal beta-hemolysin. C.
      amycolatum was the most frequently isolated nonlipophilic corynebacterium.

PMID- 10074509
TI  - Multicenter comparison of the digene hybrid capture CMV DNA assay (version 2.0),
      the pp65 antigenemia assay, and cell culture for detection of cytomegalovirus
      viremia.
AB  - We compared the Digene Hybrid Capture CMV DNA Assay version 2.0, the pp65
      antigenemia assay, traditional tube culture, and shell vial culture for the
      detection of cytomegalovirus (CMV) viremia in several patient populations at
      three centers. Of 561 blood specimens collected from 402 patients, complete
      clinical and laboratory data were available for 489. Using consensus definitions
      for true positives and true negatives, the sensitivities of the Hybrid Capture
      assay, antigenemia, shell vial, and tube culture were 95, 94, 43, and 46%,
      respectively. The specificities of the Hybrid Capture assay and antigenemia were
      95 and 94%, respectively. At all three study sites, the detected level of CMV
      viremia was significantly higher with the Hybrid Capture assay or antigenemia
      than with shell vial and tube culture. In a group of 131 healthy
      nonimmunosuppressed volunteers, the Hybrid Capture assay demonstrated a
      specificity of over 99%. The Hybrid Capture assay is a standardized assay that is
      simple to perform and can utilize whole blood specimens that have been stored for
      up to 48 h. The high sensitivity and specificity of the Hybrid Capture assay
      along with its simplicity and flexibility make it a clinically useful assay for
      the detection of CMV viremia in immunocompromised or immunosuppressed patients.
      Further evaluation to determine its role in predicting CMV disease and for
      monitoring the therapeutic response to anti-CMV therapy is needed.

PMID- 10074510
TI  - Identification of Mycobacterium kansasii by using a DNA probe (AccuProbe) and
      molecular techniques.
AB  - The newly formulated Mycobacterium kansasii AccuProbe was evaluated, and the
      results obtained with the new version were compared to the results obtained with
      the old version of this test by using 116 M. kansasii strains, 1 Mycobacterium
      gastri strain, and 19 strains of several mycobacterial species. The sensitivity
      of this new formulation was 97.4% and the specificity was 100%. Still, three M.
      kansasii strains were missed by this probe. To evaluate the variability within
      the species, genetic analyses of the hsp65 gene, the spacer sequence between the
      16S and 23S rRNA genes, and the 16S rRNA gene of several M. kansasii AccuProbe
      positive strains as well as all AccuProbe-negative strains were performed.
      Genetic analyses of the one M. gastri strain from the comparative assay and of
      two further M. gastri strains were included because of the identity of the 16S
      rRNA gene in M. gastri to that in M. kansasii. The data confirmed the genetic
      heterogeneity of M. kansasii. Furthermore, a subspecies with an unpublished hsp65
      restriction pattern and spacer sequence was described. The genetic data indicate
      that all M. kansasii strains missed by the AccuProbe test belong to one
      subspecies, the newly described subspecies VI, as determined by the hsp65
      restriction pattern and the spacer sequence. Since the M. kansasii strains that
      are missed are rare and all M. gastri strains are correctly negative, the new
      formulated AccuProbe provides a useful tool for the identification of M.
      kansasii.

PMID- 10074511
TI  - Molecular markers demonstrate that the first described multidrug-resistant
      Mycobacterium bovis outbreak was due to Mycobacterium tuberculosis.
AB  - We genetically characterized multidrug-resistant Mycobacterium tuberculosis
      complex strains which caused a nosocomial outbreak of tuberculosis affecting six
      human immunodeficiency virus (HIV)-positive patients and one HIV-negative staff
      member (E. Bouvet, E. Casalino, G. Mendoza-Sassi, S. Lariven, E. Vallee, M.
      Pernet, S. Gottot, and F. Vachon, AIDS 7:1453-1460, 1993). The strains showed all
      the phenotypic characteristics of Mycobacterium bovis. They presented a high copy
      number of IS6110, the spacers 40 to 43 in the direct repeat locus, and the mtp40
      fragment. They lacked the G-A mutation at position 285 in the oxyR gene and the C
      G mutation at position 169 in the pncA gene. These genetic characteristics
      revealed that these were dysgonic, slow-growing M. tuberculosis strains mimicking
      the M. bovis phenotype, probably as a consequence of cellular alterations
      associated with the multidrug resistance. Spoligotyping and IS6110 restriction
      fragment length polymorphism (RFLP) analysis confirmed that the outbreak was due
      to a single strain. However, the IS6110 RFLP pattern of the strain isolated from
      the last patient, diagnosed three years after the index case, differed slightly
      from the patterns of the other six strains. A model of a possible genetic event
      is presented to explain this divergence. This study stresses the value of using
      several independent molecular markers to identify multidrug-resistant tubercle
      bacilli.

PMID- 10074512
TI  - Mailed, home-obtained urine specimens: a reliable screening approach for
      detecting asymptomatic Chlamydia trachomatis infections.
AB  - The use of mailed, home-obtained urine specimens could facilitate screening
      programs for the detection of asymptomatic Chlamydia trachomatis infections.
      Since transport time could have an adverse effect on the sensitivity of C.
      trachomatis detection by PCR, the influence of DNA degradation on amplification
      was monitored over the course of 1 week. Therefore, urine specimens were
      aliquoted on the day of collection or arrival. Two groups of urine specimens were
      investigated. Group I contains first-void C. trachomatis-positive and -negative
      urine samples. DNA degradation was monitored in group I samples for 7 days at
      room temperature (RT) and at 4 degrees C by amplifying different lengths of the
      human beta-globin gene and the C. trachomatis plasmid target. DNA degradation was
      observed only for the larger human beta-globin fragments at days 5 to 7 at RT. In
      contrast, at 4 degrees C all targets could be amplified. Urine specimens were
      also frozen and thawed before aliquoting to mimic freezing during transport. This
      resulted in a lower sensitivity for the detection of C. trachomatis after thawing
      and 3 to 4 days at RT. In addition, mailed, home-obtained C. trachomatis-positive
      urine specimens (group II) were analyzed for 7 days after arrival by two
      commercially available C. trachomatis detection systems (PCR and ligase chain
      reaction [LCR]). The C. trachomatis plasmid target in mailed, home-obtained urine
      specimens could be amplified by both PCR and LCR after 1 week of storage and/or
      transport at RT. In conclusion, our findings indicate that mailed, home-obtained
      urine specimens are suitable for the sensitive detection of asymptomatic C.
      trachomatis infections by amplification methods, even if the transport time is up
      to 1 week at RT. These findings support the feasibility and validity of screening
      programs based on mailed, home-obtained urine specimens. Larger studies should be
      initiated to confirm our results.

PMID- 10074513
TI  - Detection of cell wall mannoprotein Mp1p in culture supernatants of Penicillium
      marneffei and in sera of penicilliosis patients.
AB  - Mannoproteins are important and abundant structural components of fungal cell
      walls. The MP1 gene encodes a cell wall mannoprotein of the pathogenic fungus
      Penicillium marneffei. In the present study, we show that Mp1p is secreted into
      the cell culture supernatant at a level that can be detected by Western blotting.
      A sensitive enzyme-linked immunosorbent assay (ELISA) developed with antibodies
      against Mp1p was capable of detecting this protein from the cell culture
      supernatant of P. marneffei at 10(4) cells/ml. The anti-Mp1p antibody is specific
      since it fails to react with any protein-form lysates of Candida albicans,
      Histoplasma capsulatum, or Cryptococcus neoformans by Western blotting. In
      addition, this Mp1p antigen-based ELISA is also specific for P. marneffei since
      the cell culture supernatants of the other three fungi gave negative results.
      Finally, a clinical evaluation of sera from penicilliosis patients indicates that
      17 of 26 (65%) patients are Mp1p antigen test positive. Furthermore, a Mp1p
      antibody test was performed with these serum specimens. The combined antibody and
      antigen tests for P. marneffei carry a sensitive of 88% (23 of 26), with a
      positive predictive value of 100% and a negative predictive value of 96%. The
      specificities of the tests are high since none of the 85 control sera was
      positive by either test.

PMID- 10074514
TI  - Rapid and sensitive quantification of Borrelia burgdorferi-infected mouse tissues
      by continuous fluorescent monitoring of PCR.
AB  - The quantity of Borrelia burgdorferi organisms in tissue samples is an important
      determinant for infection studies in the mouse model of Lyme disease. This report
      presents the development of a rapid and sensitive external-standard-based PCR
      assay for the absolute quantification of B. burgdorferi in mouse tissue samples.
      The assay uses a double-stranded DNA dye to continuously monitor product
      formation and in less than an hour was able to quantify samples ranging up to 6
      log units in concentration. The PCR efficiencies of the sample and the standard
      were matched by using a standard composed of purified B. burgdorferi chromosome
      mixed with tissue-matched mouse genome lacking bacterial DNA. Normalization of B.
      burgdorferi quantities to the mouse nidogen gene allowed comparison of B.
      burgdorferi numbers in samples isolated from different tissues and strains. PCR
      analysis of the chromosomal gene recA in cultured B. burgdorferi was consistent
      with a single recA per bacterium. The parameters defined in this assay should be
      applicable to quantification of other organisms, even infectious agents for which
      no ready source of DNA standard is available. In summary, this report presents a
      rapid external-standard-based PCR method for the quantification of B. burgdorferi
      in mouse DNA samples.

PMID- 10074515
TI  - Detection of Bartonella henselae DNA by two different PCR assays and
      determination of the genotypes of strains involved in histologically defined cat
      scratch disease.
AB  - Cat scratch disease (CSD) is a common cause of subacute regional lymphadenopathy,
      not only in children but also in adults. Serological and molecular studies
      demonstrated that Bartonella henselae is the etiologic agent in most cases of
      CSD. Amplification of B. henselae DNA in affected tissue and detection of
      antibodies to B. henselae are the two mainstays in the laboratory diagnosis of
      CSD. We designed a retrospective study and investigated formalin-fixed, paraffin
      embedded lymph nodes from 60 patients (25 female, 35 male) with histologically
      suspected CSD by PCR amplification. The sensitivities of two different PCR assays
      were compared. The first primer pair amplified a 296-bp fragment of the 16S rRNA
      gene in 36 of the 60 samples, corresponding to a sensitivity of 60%. The second
      primer pair amplified a 414-bp fragment of the htrA gene in 26 of the 60 lymph
      nodes, corresponding to a sensitivity of 43.3%. Bartonella DNA could be detected
      in a total of 39 (65%) of the 60 lymph nodes investigated. However,
      histopathologic findings are typical but not specific for CSD and cannot be
      considered as a "gold standard" for diagnosis of CSD. The sensitivity of the PCR
      assays increased from 65 to 87% if two criteria (histology and serology) were
      used in combination for diagnosis of CSD. Two genotypes (I and II) of B. henselae
      are described as being involved in CSD. Genotype I was found in 23 (59%) and
      genotype II was found in 9 (23%) of the 39 PCR-positive lymph nodes. Seven (18%)
      lymph nodes were negative in both type-specific PCR assays. Thirty (50%) of our
      60 patients were younger than 20 years old (15 were younger than 10 years), 20
      (33%) were between 21 and 40 years old, and 10 (17%) patients were between 41 and
      84 years old. Our data suggest that detection of Bartonella DNA in patients'
      samples might confirm the histologically suspected diagnosis of CSD.

PMID- 10074516
TI  - Molecular evidence for heterogeneity of the multiple-drug-resistant Mycobacterium
      tuberculosis population in Scotland (1990 to 1997).
AB  - Multiple-drug-resistant Mycobacterium tuberculosis (MDR-MTB) has been well
      studied in hospitals or health care institutions and in human immunodeficiency
      virus-infected populations. However, the characteristics of MDR-MTB in the
      community have not been well investigated. An understanding of its prevalence and
      circulation within the community will help to estimate the problem and optimize
      the strategies for control and prevention of its development and transmission. In
      this study, MDR-MTB isolates from Scotland collected between 1990 and 1997 were
      characterized, along with non-drug-resistant isolates. The results showed that
      they were genetically diverse, suggesting they were unrelated to each other and
      had probably evolved independently. Several new alleles of rpoB, katG, and ahpC
      were identified: rpoB codon 525 (ACC-->AAC; Thr525Asn); katG codon 128 (CGG-
      >CAG; Arg128Gln) and codon 291 (GCT-->CCT; Ala291Pro); and the ahpC synonymous
      substitution at codon 6 (ATT-->ATC). One of the MDR-MTB isolates from an Asian
      patient had an IS6110 restriction fragment length polymorphism pattern very
      similar to that of the MDR-MTB W strain and had the same drug resistance-related
      alleles but did not have any epidemiological connection with the W strains.
      Additionally, a cluster of M. tuberculosis isolates was identified in our
      collection of 715 clinical isolates; the isolates in this cluster had genetic
      backgrounds very similar to those of the W strains, one of which had already
      developed multiple drug resistances. The diverse population of MDR-MTB in
      Scotland, along with a low incidence of drug-resistant M. tuberculosis, has
      implications for the control of the organism and prevention of its spread.

PMID- 10074517
TI  - Comparison of isolation media for recovery of Burkholderia cepacia complex from
      respiratory secretions of patients with cystic fibrosis.
AB  - Burkholderia cepacia selective agar (BCSA) has previously been devised for
      isolation of B. cepacia from respiratory secretions of patients with cystic
      fibrosis and tested under research laboratory conditions. Here we describe a
      study in which BCSA, oxidation-fermentation polymyxin bacitracin lactose agar
      (OFPBL), and Pseudomonas cepacia agar (PCA) were compared in routine culture
      procedures for the ability to grow B. cepacia and inhibit other organisms. Three
      hundred twenty-eight specimens from 209 patients at two pediatric centers and 328
      specimens from 109 adults were tested. Plates were inoculated, incubated, and
      read for quality and quantity of growth at 24, 48, and 72 h. Five (1.5%)
      specimens from 4 (1.9%) children and 75 (22.9%) specimens from 16 (14.7%) adults
      grew B. cepacia complex. At 24, 48, and 72 h, BCSA achieved 43, 93, and 100%
      detection, respectively; OFPBL achieved 26, 84, and 96%, respectively; and PCA
      achieved 33, 74, and 84% detection, respectively. Quality was assessed as
      pinpoint or good growth. At 24 h, most cultures growing B. cepacia complex had
      pinpoint colonies. By 48 and 72 h, 48 and 69% of B. cepacia complex cultures,
      respectively, had good growth on BCSA, while on OFPBL 19 and 30%, respectively,
      had good growth and on PCA 11 and 18%, respectively, had good growth. BCSA was
      superior to OFPBL and PCA in suppressing organisms other than B. cepacia complex;
      40 non-B. cepacia complex organisms were isolated from BCSA, 263 were isolated
      from OFPBL, and 116 were isolated from PCA. We conclude that BCSA is superior to
      OFPBL and PCA in its ability to support the growth of B. cepacia complex and to
      suppress other respiratory organisms.

PMID- 10074518
TI  - Comparison of large restriction fragments of Mycobacterium avium isolates
      recovered from AIDS and non-AIDS patients with those of isolates from potable
      water.
AB  - We examined potable water in Los Angeles, California, as a possible source of
      infection in AIDS and non-AIDS patients. Nontuberculous mycobacteria were
      recovered from 12 (92%) of 13 reservoirs, 45 (82%) of 55 homes, 31 (100%) of 31
      commercial buildings, and 15 (100%) of 15 hospitals. Large-restriction-fragment
      (LRF) pattern analyses were done with AseI. The LRF patterns of Mycobacterium
      avium isolates recovered from potable water in three homes, two commercial
      buildings, one reservoir, and eight hospitals had varying degrees of relatedness
      to 19 clinical isolates recovered from 17 patients. The high number of M. avium
      isolates recovered from hospital water and their close relationship with clinical
      isolates suggests the potential threat of nosocomial spread. This study supports
      the possibility that potable water is a source for the acquisition of M. avium
      infections.

PMID- 10074519
TI  - Coronary angioplasty induces rise in Chlamydia pneumoniae-specific antibodies.
AB  - Chlamydia pneumoniae is frequently found in atherosclerotic lesions, and high
      titers of specific antibodies are associated with increased risk for acute
      myocardial infarction. However, a causative relation has not been established
      yet. We performed a prospective study of 93 patients undergoing percutaneous
      transluminal coronary angioplasty (PTCA) to investigate whether angioplasty
      influences Chlamydia-specific antibody titers and whether there is an association
      with restenosis. Blood samples were obtained before and 1 and 6 months after
      angioplasty. Antibodies against chlamydial lipopolysaccharide and against
      purified C. pneumoniae elementary bodies were measured by enzyme-linked
      immunosorbent assay (ELISA). After angioplasty, the prevalence of antibodies to
      lipopolysaccharide rose from 20 to 26% for immunoglobulin A (IgA), from 53 to 64%
      for IgG, and from 2 to 7% for IgM (P = 0.021, 0.004, and 0.046, respectively).
      There was a rapid increase of mean antibody titers of all antibody classes within
      1 month of PTCA. During the following 5 months, antibody titers decreased
      slightly but were still higher than baseline values. Results of the C. pneumoniae
      specific ELISA were essentially the same. The rise of anti-Chlamydia antibodies
      was not caused by unspecific reactivation of the immune system, as levels of
      antibodies against cytomegalovirus did not change. Neither seropositivity nor
      antibody titers were related to restenosis. However, increases in mean IgA and
      IgM titers were restricted to patients who had suffered from myocardial
      infarction earlier in their lives. In conclusion, we show that PTCA induces a
      stimulation of the humoral immune response against C. pneumoniae. These data
      support the idea that plaque disruption during angioplasty might make hidden
      chlamydial antigens accessible to the immune system.

PMID- 10074520
TI  - Identification and characterization of IS2404 and IS2606: two distinct repeated
      sequences for detection of Mycobacterium ulcerans by PCR.
AB  - Molecular analysis of Mycobacterium ulcerans has revealed two new insertion
      sequences (ISs), IS2404 and IS2606. IS2404 was identified by complete sequencing
      of a previously described repetitive DNA segment from M. ulcerans. This element
      is 1,274 bp long, contains 12-bp inverted repeats and a single open reading frame
      (ORF) potentially encoding a protein of 327 amino acids (aa), and apparently
      generates 7-bp direct repeats upon transposition. Amino acid similarity was found
      between the putative transposase and those encoded by ISs in other bacterial
      sequences from Aeromonas salmonicida (AsIs1), Escherichia coli (H repeat
      element), Vibrio cholerae (VcIS1), and Porphyromonas gingivalis (PGIS2). The
      second IS, IS2606, was discovered by sequence analysis of a HaeIII fragment of M.
      ulcerans genomic DNA containing a repetitive sequence. This element is 1,404 bp
      long, with 12-bp inverted repeats and a single ORF potentially encoding a protein
      of 445 aa. Database searches revealed a high degree of amino acid identity (70%)
      with the putative transposase of IS1554 from M. tuberculosis. Significant amino
      acid identity (40%) was also observed with transposases from several other
      microorganisms, including Rhizobium meliloti (ISRm3), Burkholderia cepacia
      (IS1356), Corynebacterium diphtheriae, and Yersinia pestis. PCR screening of DNA
      from 45 other species of mycobacteria with primers for IS2404 confirm that this
      element is found only in M. ulcerans. However, by PCR, IS2606 was also found in
      Mycobacterium lentiflavum, another slow-growing member of the genus Mycobacterium
      that is apparently genetically distinct from M. ulcerans. Testing the sensitivity
      of PCR based on IS2404 and IS2606 primers demonstrated the ability to detect 0.1
      and 1 M. ulcerans genome equivalents, respectively. The ability to detect small
      numbers of cells by using two gene targets will be particularly useful for
      analyzing environmental samples, where there may be low concentrations of M.
      ulcerans among large numbers of other environmental mycobacteria.

PMID- 10074521
TI  - Indirect enzyme-linked immunosorbent assay for detection of immunoglobulin G
      reactive with a recombinant protein expressed from the gene encoding the 116
      kilodalton protein of Mycoplasma pneumoniae.
AB  - Serology remains the method of choice for laboratory diagnosis of Mycoplasma
      pneumoniae infection. Currently available serological tests employ complex
      cellular fractions of M. pneumoniae as antigen. To improve the specificity of M.
      pneumoniae diagnosis, a recombinant protein was assessed as a serodiagnostic
      reagent. A panel of recombinant proteins were expressed from a cloned M.
      pneumoniae gene that encodes a 116-kDa surface protein antigen. The recombinant
      proteins were assessed for reactivity with patient sera and the most antigenic
      was further assessed for its serodiagnostic potential by indirect enzyme-linked
      immunosorbent assay (ELISA). The ELISA based on the recombinant protein was
      equivalent in sensitivity to the commercial test (Serodia Myco II; Fujirebio
      Inc.) to which it was compared. Southern and Western blotting data suggested that
      the recombinant protein derived from the 116-kDa protein of M. pneumoniae could
      provide a species-specific diagnostic tool, although further assessment is
      required.

PMID- 10074522
TI  - Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical
      disease and HPV type.
AB  - The association between human papillomavirus (HPV) DNA copy number and cervical
      disease was investigated. Viral DNA copy number for the most common high-risk HPV
      types in cervical cancer (types 16, 18, 31, and 45) was determined in cervical
      cytobrush specimens from 149 women with high-grade cervical intraepithelial
      neoplasias (CIN II-CIN III), 176 with low-grade CIN (CIN I), and 270 with normal
      cytology. Quantitative, PCR-based fluorescent assays for each of the HPV
      genotypes and for the beta-globin gene were used. The amount of cellular DNA
      increased significantly with increasing disease; thus, HPV was expressed as
      copies per microgram of cellular DNA. The assay had a dynamic range of >10(7),
      allowing documentation for the first time of the wide range of HPV copy numbers
      seen in clinical specimens. Median HPV DNA copy number varied by more than 10(4)
      among the viral types. HPV16 was present in the highest copy number; over 55% of
      HPV16-positive samples contained more than 10(8) copies/microgram. Median copy
      number for HPV16 showed dramatic increases with increasing epithelial
      abnormality, an effect not seen with the other HPV types. HPV16 increased from a
      median of 2.2 x 10(7) in patients with normal cytology, to 4.1 x 10(7) in CIN I
      patients, to 1.3 x 10(9) copies/microgram in CIN II-III patients. Even when
      stratified by cervical disease and viral type, the range of viral DNA copies per
      microgram of cellular DNA was quite large, precluding setting a clinically
      significant cutoff value for "high" copy numbers predictive of disease. This
      study suggests that the clinical usefulness of HPV quantitation requires
      reassessment and is assay dependent.

PMID- 10074523
TI  - Development and characterization of complex DNA fingerprinting probes for the
      infectious yeast Candida dubliniensis.
AB  - Using a strategy to clone large genomic sequences containing repetitive elements
      from the infectious yeast Candida dubliniensis, the three unrelated sequences
      Cd1, Cd24, and Cd25, with respective molecular sizes of 15,500, 10,000, and
      16,000 bp, were cloned and analyzed for their efficacy as DNA fingerprinting
      probes. Each generated a complex Southern blot hybridization pattern with
      endonuclease-digested genomic DNA. Cd1 generated an extremely variable pattern
      that contained all of the bands of the pattern generated by the repeat element
      RPS of Candida albicans. We demonstrated that Cd1 does not contain RPS but does
      contain a repeat element associated with RPS throughout the C. dubliniensis
      genome. The Cd1 pattern was the least stable over time both in vitro and in vivo
      and for that reason proved most effective in assessing microevolution. Cd24,
      which did not exhibit microevolution in vitro, was highly variable in vivo,
      suggesting in vivo-dependent microevolution. Cd25 was deemed the best probe for
      broad epidemiological studies, since it was the most stable over time, was the
      only truly C. dubliniensis-specific probe of the three, generated the most
      complex pattern, was distributed throughout all C. dubliniensis chromosomes, and
      separated a worldwide collection of 57 C. dubliniensis isolates into two distinct
      groups. The presence of a species-specific repetitive element in Cd25 adds weight
      to the already substantial evidence that C. dubliniensis represents a bona fide
      species.

PMID- 10074524
TI  - Helicobacter pylori can be induced to assume the morphology of Helicobacter
      heilmannii.
AB  - Cultures of Helicobacter pylori obtained from the American Type Culture
      Collection (strain 43504) were grown as isolated colonies or lawns on blood agar
      plates and in broth culture with constant shaking. Examination of bacterial
      growth with Gram-stained fixed preparation and differential interference contrast
      microscopy on wet preparations revealed that bacteria grown on blood agar plates
      had a morphology consistent with that normally reported for H. pylori whereas
      bacteria from broth cultures had the morphologic appearance of Helicobacter
      heilmannii. Bacteria harvested from blood agar plates assumed an H. heilmannii
      like morphology when transferred to broth cultures, and bacteria from broth
      cultures grew with morphology typical of H. pylori when grown on blood agar
      plates. Analysis by PCR of bacteria isolated from blood agar plates and broth
      cultures indicated that a single strain of bacteria (H. pylori) was responsible
      for both morphologies.

PMID- 10074525
TI  - Rapid and sensitive detection of immunoglobulin M (IgM) and IgG antibodies
      against canine distemper virus by a new recombinant nucleocapsid protein-based
      enzyme-linked immunosorbent assay.
AB  - Canine distemper morbillivirus (CDV) infection causes a frequently fatal systemic
      disease in a broad range of carnivore species, including domestic dogs. In CDV
      infection, classical serology provides data of diagnostic and prognostic values
      (kinetics of seroconversion) and is also used to predict the optimal vaccination
      age of pups. Routine CDV serology is still based on time- and cost-intensive
      virus neutralization assays (V-NA). Here, we describe a new capture-sandwich
      enzyme-linked immunosorbent assay (ELISA) that uses recombinant baculovirus
      expressed nucleocapsid (N) protein of a recent CDV wild-type isolate (2544/Han95)
      for the detection of CDV-specific antibodies in canine sera. Recombinant antigen
      was produced with high efficacy in Heliothis virescens larvae. The capture
      sandwich ELISA enabled a clear-cut qualitative evaluation of the CDV-specific
      immunoglobulin G (IgG) and IgM serostatuses of 196 and 35 dog sera, respectively.
      Inter-rater agreement analysis (kappa = 0.988) indicated that the ELISA can be
      used unrestrictedly as a substitute for the V-NA for the qualitative
      determination of CDV-specific IgG serostatus. In an attempt to semiquantify N
      specific antibodies, a one-step-dilution (alpha method) IgG-specific ELISA was
      implemented. Alpha values of >/=50% showed very good inter-rater agreement (kappa
      = 0.968) with V-NA titers of >/=1/100 50% neutralizing dose (ND50) as measured
      against the central European CDV wild-type isolate 2544/Han95 in canine sera
      originating from northern Germany. An ND50 titer of 1/100 is considered a
      threshold, and titers of >/=1/100 indicate a resilient, protective immunity. CDV
      N-specific antibodies of the IgM class were detected by the newly developed ELISA
      in 9 of 15 sera obtained from dogs with symptoms of acute distemper. In
      leucocytes of 5 of the 15 dogs (all of which were also IgM positive) CDV RNA was
      detected by reverse transcription (RT)-PCR. The recombinant capture-sandwich
      ELISA detecting N-specific antibodies of the IgG class provided superior
      sensitivity and specificity and thus represents a rapid and cost-effective
      alternative to classical CDV V-NA. By detection of specific IgM antibodies, the
      ELISA will be complementary to RT-PCR and V-NA in the diagnosis of acute
      distemper infections.

PMID- 10074526
TI  - Use of PCR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      techniques for differentiation of Prevotella intermedia sensu stricto and
      Prevotella nigrescens.
AB  - Primers were designed from 16S rRNA sequences of Prevotella intermedia sensu
      stricto and Prevotella nigrescens and were used to discriminate these two species
      by PCR. The results were compared with those from the PCR technique using primers
      designed from arbitrarily primed PCR products by Guillot and Mouton (E. Guillot
      and C. Mouton, J. Clin. Microbiol. 35:1876-1882, 1997). The specificities of both
      assays were studied by using P. intermedia ATCC 25611, P. nigrescens ATCC 33563,
      174 clinical isolates of P. intermedia sensu lato, and 59 reference strains and
      58 clinical isolates of other Prevotella species and/or common oral flora. In
      addition, the usefulness and reliability of sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) in the differentiation of the two species were
      examined by comparing the results with those from PCR assays. The controversial
      lipase test for distinguishing these species was also carried out. Unambiguous
      differentiation was made by both PCR assays, and the results matched each other.
      The SDS-PAGE assay was found to misidentify a few strains tested, compared with
      the results of PCR assays. The lipase test was positive for both species,
      including the reference strains of P. intermedia and P. nigrescens. We conclude
      that both PCR assays are simple, rapid, reliable, and specific methods which
      could be used in clinical studies and that the lipase test is not valuable in the
      differentiation. The reliable discrimination of the two species by SDS-PAGE is
      questionable.

PMID- 10074527
TI  - Analysis with a combination of macrorestriction endonucleases reveals a high
      degree of polymorphism among Bordetella pertussis isolates in eastern France.
AB  - From 1990 to 1996, routine screening for whooping cough identified 399 patients
      with a calmodulin-dependent adenylate cyclase-positive test result and yielded 69
      Bordetella pertussis isolates. None of the patients were fully vaccinated, and
      most were less than 6 months old. Analysis of total DNA by pulsed-field gel
      electrophoresis (PFGE) after XbaI, SpeI, or DraI macrorestriction yielded 19, 15,
      and 5 different patterns, respectively, whereas ribotyping failed to demonstrate
      any strain polymorphism. Discrimination among the isolates was improved by
      combining the PFGE profiles. Some patterns were more frequent, but the
      corresponding patients were not clearly epidemiologically related. The patterns
      for two strains obtained during a 3-month period from patients who were neighbors
      differed by the length of a single DNA fragment. These data strongly suggest that
      one type of isolate is widely spread throughout the world and is carried by
      individuals other than patients who develop a true illness.

PMID- 10074528
TI  - Characterization of a culturable "Gastrospirillum hominis" (Helicobacter
      heilmannii) strain isolated from human gastric mucosa.
AB  - Spiral organisms were isolated from an antral gastric mucosal biopsy specimen
      from a dyspeptic patient with gastritis. Only corkscrew-shaped organisms
      resembling "Gastrospirillum hominis" ("Helicobacter heilmannii") but no
      Helicobacter pylori-like organisms were seen in histological sections. H. pylori
      was not cultured from specimens from this patient. On the basis of biochemical
      reactions, morphology, ultrastructure, and 16S DNA sequencing, the isolated "G.
      hominis" was shown to be a true Helicobacter sp. very similar to Helicobacter
      felis and the "Gastrospirillum" but was separate from H. pylori. "G. hominis" is
      a pleomorphic gram-negative cork-screw-shaped, motile rod with 3 to 8 coils and a
      wavelength of about 1 micrometer. In contrast to H. pylori, it has up to 14
      sheathed flagellar uni- or bipolar fibrils but no periplasmic fibrils. "G.
      hominis" grows under microaerobic conditions at 36 and 41 degrees C on 7% lysed,
      defibrinated horse blood agar plates within 3 to 7 days and can be subcultured
      under microaerobic but not under anaerobic conditions on media similar to those
      used for H. pylori and H. felis. The small translucent colonies were, in contrast
      to those of H. felis, indistinguishable from those of H. pylori. "G. hominis" is,
      like H. pylori and H. felis, motile, is oxidase, catalase, nitrite, nitrate, and
      urease positive, and produces alkaline phosphatase and arginine arylamidase. Like
      H. pylori and H. felis, it is sensitive to cephalothin (30-microgram disc),
      resistant to nalidixic acid (30-microgram disc), and sensitive to most other
      antibiotics. The 16S DNA sequence clusters "G. hominis" together with
      "Gastrospirillum," H. felis, Helicobacter bizzozeronii, Helicobacter salmonii,
      Helicobacter nemestrinae, Helicobacter acinonychis, and H. pylori.

PMID- 10074529
TI  - Evaluation of modified BACTEC 12B radiometric medium and solid media for culture
      of Mycobacterium avium subsp. paratuberculosis from sheep.
AB  - Definitive diagnosis of Johne's disease in ruminants depends on confirming the
      presence of the causative bacterium, Mycobacterium avium subsp. paratuberculosis,
      in tissues of the host. This is readily achieved in most ruminant species by
      culture. However, culture of clinical specimens from sheep in many countries has
      been unrewarding. Such a culture from sheep was achieved recently in Australia by
      using a radiometric culture medium. The aims of the present study were to
      evaluate the culture of M. avium subsp. paratuberculosis from sheep by using
      modified BACTEC 12B radiometric medium, to determine the sensitivity of culture
      in relation to histopathology, and to evaluate a range of solid media. Culture of
      M. avium subsp. paratuberculosis from sheep with Johne's disease is a sensitive
      method of diagnosis: intestinal tissues from all 43 animals with multibacillary
      disease and all 22 animals with paucibacillary disease were culture positive,
      while 98% of feces from 53 animals with multibacillary disease and 48% of feces
      from 31 animals with paucibacillary disease were culture positive. Of sheep
      without histological evidence of Johne's disease from infected flocks, intestinal
      tissue from 32% of 41 were culture positive, while feces from 17% of 41 were
      culture positive. Consequently, culture is recommended as the "gold standard"
      test for detection of ovine Johne's disease. Of the wide range of solid media
      that were evaluated, only modified Middlebrook 7H10 and 7H11 agars, which were
      very similar in composition to modified BACTEC 12B medium, yielded growth of
      ovine strains of M. avium subsp. paratuberculosis. The sensitivity of detection
      of M. avium subsp. paratuberculosis on solid media was slightly lower than that
      in modified BACTEC 12B radiometric medium. Both egg yolk and mycobactin J were
      essential additives for growth of ovine strains of M. avium subsp.
      paratuberculosis in both liquid and solid media.

PMID- 10074530
TI  - DNA banding pattern polymorphism in vancomycin-resistant Enterococcus faecium and
      criteria for defining strains.
AB  - The degree of DNA banding pattern polymorphism exhibited by vancomycin-resistant
      Enterococcus faecium (VREM) strains isolated on a renal unit over an 11-month
      period was investigated. Thirty VREM strains from different patients were
      analyzed by pulsed-field gel electrophoresis (PFGE; with extended run and optimal
      pulse times), ribotyping, plasmid profile analysis, biotyping, pyrolysis mass
      spectrometry, and antibiogram analysis. PFGE resolved 17 banding patterns which
      formed four distinct clusters at the 82% similarity level. Intercluster band
      differences ranged from 14 to 31 bands. The strains in one cluster, which
      contained seven patterns that differed from each other by one to seven bands and
      from the common pattern by five bands, were confirmed to be a single strain by
      four of the five other typing methods. The strains in a second cluster with eight
      patterns, which differed from each other by 1 to 12 bands, contained two
      subclusters. This subdivision was supported by ribotyping and biotyping. However,
      it was unclear whether these subclusters represented distinct strains. In one
      strain, marked polymorphism (patterns that differed from each other by up to four
      bands) was observed in the ribotype pattern. This study demonstrates the high
      degree of DNA banding pattern polymorphism found for some strains of VREM and
      illustrates the complexity involved in defining such strains.

PMID- 10074531
TI  - Use of molecular subtyping to document long-term persistence of Corynebacterium
      diphtheriae in South Dakota.
AB  - Enhanced surveillance of patients with upper respiratory symptoms in a Northern
      Plains community revealed that approximately 4% of them were infected by
      toxigenic Corynebacterium diphtheriae of both mitis and gravis biotypes, showing
      that the organism is still circulating in the United States. Toxigenic C.
      diphtheriae was isolated from five members of four households. Four molecular
      subtyping methods-ribotyping, multilocus enzyme electrophoresis (MEE), random
      amplified polymorphic DNA (RAPD), and single-strand conformation polymorphism
      were used to molecularly characterize these strains and compare them to 17
      archival South Dakota strains dating back to 1973 through 1983 and to 5 isolates
      collected from residents of diverse regions of the United States. Ribotyping and
      RAPD clearly demonstrated the household transmission of isolates and provided
      precise information on the circulation of several distinct strains within three
      households. By MEE, most recent and archival South Dakota strains were identified
      as closely related and clustered within the newly identified ET (electrophoretic
      type) 215 complex. Furthermore, three recent South Dakota isolates and eight
      archival South Dakota isolates were indistinguishable by both ribotyping and
      RAPD. All of these molecular methods showed that recent South Dakota isolates and
      archival South Dakota isolates were more closely related to each other than to
      the C. diphtheriae strains isolated in other parts of the United States or
      worldwide. The data also supported the improbability of importation of C.
      diphtheriae into this area and rather strongly suggest the long-term persistence
      of the organism in this region.

PMID- 10074532
TI  - Human immunodeficiency virus antibody testing by enzyme-linked fluorescent and
      western blot assays using serum, gingival-crevicular transudate, and urine
      samples.
AB  - The aim of the present study was to evaluate the possible utilization of saliva
      and urine as alternative samples to serum for the diagnosis of human
      immunodeficiency virus (HIV) infection. A total of 302 individuals participated
      in the study: 187 HIV-infected individuals (106 had Centers for Disease Control
      and Prevention [CDC] stage II infection, 19 had CDC stage III infection, and 62
      had CDC stage IV infection) and 115 noninfected persons (46 of the noninfected
      persons were blood donors and 69 belonged to a group at high risk of HIV
      infection). Paired saliva and urine samples were taken from each of the
      participants in the study. The presence of HIV-specific antibodies was detected
      by an enzyme-linked fluorescent assay (ELFA), and the result was confirmed by
      Western blot analysis (WB). The ELFA with saliva gave maximum sensitivity and
      specificity values, while ELFA had lower sensitivity (95.2%) and specificity (97.
      4%) values for detection of HIV antibody in urine samples. WB with all saliva
      samples fulfilled the World Health Organization criterion for positivity, while
      only 96.8% of the urine samples were confirmed to be positive by WB. Among the
      four reactivity patterns found by WB of these alternative samples, the most
      frequent included bands against three groups of HIV structural proteins (was ENV,
      POL, and GAG). The reactivity bands most frequently observed were those for the
      proteins gp160 and gp120. The least common reactivity band was the band for
      protein p17. The detection of HIV antibodies in saliva samples by means of ELFA
      with the possibility of later confirmation by WB makes saliva an alternative to
      serum for possible use in the diagnosis of infection. In contrast, HIV antibody
      detection in urine samples by the same methodology (ELFA) could be taken into
      consideration for use in epidemiological studies.

PMID- 10074533
TI  - Strain variation in adenovirus serotypes 4 and 7a causing acute respiratory
      disease.
AB  - In order to determine the suitability of vaccine strains established in the 1960s
      for a new vaccine, a comprehensive study of strain variation of adenovirus
      serotype 4 (AV 4) and AV 7 was undertaken. A 1,500-bp region of the hexon gene
      containing the AV neutralization epitopes from prototype, vaccine, and community
      acquired strains and from wild-type strains from military personnel that cause
      acute respiratory disease (ARD) was sequenced and analyzed. The whole hexon gene
      from prototype strains, vaccine strains, and selected isolates was sequenced. AV
      7 and AV 7a were found to have distinct genotypes, and all vaccine and wild-type
      strains recovered from 1963 to 1997 had the AV 7a genotype. There was no
      significant strain variation in the neutralization epitopes of the AV 7a genotype
      over a 42-year period. The evolution of AV 4 was more complex, with continuous
      genetic drift punctuated by replacement with a new strain. The current strain of
      AV 4, which has been in circulation since 1995, is significantly different from
      the AV 4 prototype and the vaccine strains. Genetic differences were confirmed to
      be antigenic differences by neutralization tests, which define the new strain as
      an AV 4 variant. A type-specific PCR for AV 4, AV 7/7a, and AV 21 was developed,
      and this PCR facilitated the rapid identification of isolates from outbreaks of
      ARD.

PMID- 10074534
TI  - Detection of Epstein-Barr virus DNA in sera from transplant recipients with
      lymphoproliferative disorders.
AB  - Early diagnosis of Epstein-Barr Virus (EBV)-associated posttransplant
      lymphoproliferative disease (PTLD) is important because many patients respond to
      reduction in immunosuppression, especially if PTLD is detected at an early stage.
      Previous studies have found elevated EBV DNA levels in blood from patients with
      PTLD, but these assays required isolation of cellular blood fractions and
      quantitation. We evaluated the presence of cell-free EBV DNA in serum from solid
      organ transplant recipients as a marker for PTLD. Five of 6 transplant recipients
      with histopathologically documented PTLD had EBV DNA detected in serum at the
      time of diagnosis (sensitivity = 83%), compared with 0 of 16 matched transplant
      recipients without PTLD (specificity = 100%) (P < 0.001 [Fisher's exact test]).
      Furthermore, EBV DNA was detected in serum 8 and 52 months prior to the diagnosis
      of PTLD in two of three patients for whom stored sera were analyzed. Detection of
      EBV DNA in serum appears to be a useful marker for the early detection of PTLD in
      solid-organ transplant recipients. Further studies to define the role of such
      assays in evaluating solid-organ transplant patients at risk for PTLD are
      warranted.

PMID- 10074535
TI  - Bartonella koehlerae sp. nov., isolated from cats.
AB  - Two of the 25 Bartonella isolates recovered during a prevalence study of
      Bartonella henselae bacteremia in domestic cats from the greater San Francisco
      Bay region were found to differ phenotypically and genotypically from all prior
      B. henselae isolates. These isolates, C-29 and C-30, which were recovered from
      the blood of two pet cats belonging to the same household, grew on chocolate agar
      as pinpoint colonies following 14 days of incubation at 35 degrees C in a candle
      jar but failed to grow on heart infusion agar supplemented with 5% rabbit blood.
      Additional phenotypic characteristics distinguished the isolates C-29 and C-30
      from other feline B. henselae isolates. The restriction patterns obtained for C
      29 and C-30 by citrate synthase PCR-restriction fragment length polymorphism
      (RFLP) analysis as well as by genomic RFLP could not be distinguished from each
      other but were distinctly different from that of the B. henselae type strain. In
      reciprocal reactions, DNAs from strains C-29 and C-30 were 97 to 100% related
      under optimal and stringent DNA reassociation conditions, with 0 to 0.5%
      divergence within related sequences. Labeled DNA from the type strain of B.
      henselae was 61 to 65% related to unlabeled DNAs from strains C-29 and C-30 in 55
      degrees C reactions, with 5.0 to 5.5% divergence within the related sequences,
      and 31 to 41% related in stringent, 70 degrees C reactions. In reciprocal
      reactions, labeled DNAs from strains C-29 and C-30 were 68 to 92% related to
      those of the B. henselae type strain and other B. henselae strains, with 5 to 7%
      divergence. The 16S rRNA gene sequence of strain C-29 was 99.54% homologous to
      that of the type strain of B. henselae. On the basis of these findings, the two
      isolates C-29 and C-30 are designated a new species of Bartonella, for which we
      propose the name Bartonella koehlerae. The type strain of Bartonella koehlerae is
      strain C-29 (ATCC 700693).

PMID- 10074536
TI  - Comparison of Ehrlichia muris strains isolated from wild mice and ticks and
      serologic survey of humans and animals with E. muris as antigen.
AB  - In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice
      was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This
      finding suggests that the reservoir of E. muris is focal. Among the 15
      seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1
      A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10
      ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the
      E. muris type strain had been isolated. These new isolates were compared with the
      E. muris type strain. The mouse virulence and ultrastructure of the new isolates
      were similar to those of the type strain, and all of them were cross-reactive
      with each other, as well as with the type strain, by indirect immunofluorescent
      antibody test. The levels of similarity of the base sequences of the 16S rRNA
      gene of one of the A. speciosus isolates and one of the tick isolates to that of
      the E. muris type strain were 99.79 and 99.93%, respectively. We suggest that all
      of these isolates are E. muris; that E. muris is not limited to Eothenomys kageus
      but infects other species of mice; and that E. muris is present at locations
      other than Aichi Prefecture. It appears that H. flava is a potential vector of E.
      muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be
      seropositive for E. muris antibodies. A serological survey revealed that exposure
      to E. muris or organisms antigenically cross-reactive to E. muris occurred among
      dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby
      prefectures, and Nagoya City, central Japan. However, human beings and Rattus
      norvegicus rats in this area were seronegative. These results indicate broader
      geographic distribution of and human and animal species exposure to E. muris or
      related Ehrlichia spp. in Japan.

PMID- 10074537
TI  - Antimicrobial susceptibilities and plasmid contents of Neisseria gonorrhoeae
      isolates from commercial sex workers in Dhaka, Bangladesh: emergence of high
      level resistance to ciprofloxacin.
AB  - Commercial sex workers (CSWs) serve as the most important reservoir of sexually
      transmitted diseases (STD), including gonorrhea. Periodic monitoring of the
      antimicrobial susceptibility profile of Neisseria gonorrhoeae in a high-risk
      population provides essential clues regarding the rapidly changing pattern of
      antimicrobial susceptibilities. A study concerning the prevalence of gonococcal
      infection among CSWs was conducted in Bangladesh. The isolates were examined with
      regards to their antimicrobial susceptibility to, and the MICs of, penicillin,
      tetracycline, ciprofloxacin, cefuroxime, ceftriaxone, and spectinomycin by disk
      diffusion and agar dilution methods. The total plasmid profile of the isolates
      was also analyzed. Of the 224 CSWs, 94 (42%) were culture positive for N.
      gonorrhoeae. There was a good correlation between the results of the disk
      diffusion and agar dilution methods. Some 66% of the isolates were resistant to
      penicillin, and 34% were moderately susceptible to penicillin. Among the
      resistant isolates, 23.4% were penicillinase-producing N. gonorrhoeae (PPNG).
      60.6% of the isolates were resistant and 38.3% were moderately susceptible to
      tetracycline, 17.5% were tetracycline-resistant N. gonorrhoeae, 11.7% were
      resistant and 26.6% had reduced susceptibility to ciprofloxacin, 2.1% were
      resistant and 11.7% had reduced susceptibility to cefuroxime, and 1% were
      resistant to ceftriaxone. All PPNG isolates contained a 3.2-MDa African type of
      plasmid, and a 24.2-MDa conjugative plasmid was present in 34.1% of the isolates.
      Since quinolones such as ciprofloxacin are recommended as the first line of
      therapy for gonorrhea, the emergence of significant resistance to ciprofloxacin
      will limit the usefulness of this drug for treatment of gonorrhea in Bangladesh.

PMID- 10074538
TI  - Genetic diversity of the 28-kilodalton outer membrane protein gene in human
      isolates of Ehrlichia chaffeensis.
AB  - The Ehrlichia chaffeensis 28-kDa outer membrane protein (p28) gene was sequenced
      completely by genomic walking with adapter PCR. The DNA sequence of the p28 gene
      was nearly identical to the previously reported sequence (N. Ohashi, N. Zhi, Y.
      Zhang, and Y. Rikihisa, Infect. Immun. 66:132-139, 1998), but analysis of a
      further 75 bp on the 5' end of the gene revealed DNA that encoded a 25-amino-acid
      signal sequence. The leader sequence was removed from the N terminus of a 30-kDa
      precursor to generate the mature p28 protein. A monoclonal antibody (MAb), 1A9,
      recognizing four outer membrane proteins of E. chaffeensis (Arkansas strain)
      including the 25-, 26-, 27-, and 29-kDa proteins (X.-J. Yu, P. Brouqui, J. S.
      Dumler, and D. Raoult, J. Clin. Microbiol. 31:3284-3288, 1993) reacted with the
      recombinant p28 protein. This result indicated that the four proteins recognized
      by MAb 1A9 were encoded by the multiple genes of the 28-kDa protein family. DNA
      sequence alignment analysis revealed divergence of p28 among all five human
      isolates of E. chaffeensis. The E. chaffeensis strains could be divided into
      three genetic groups on the basis of the p28 gene. The first group consisted of
      the Sapulpa and St. Vincent strains. They had predicted amino acid sequences
      identical to each other. The second group contained strain 91HE17 and strain Jax,
      which only showed 0.4% divergence from each other. The third group contained the
      Arkansas strain only. The amino acid sequences of p28 differed by 11% between the
      first two groups, by 13.3% between the first and third groups, and by 13.1%
      between the second and third groups. The presence of antigenic variants of p28
      among the strains of E. chaffeensis and the presence of multiple copies of
      heterogeneous genes suggest a possible mechanism by which E. chaffeensis might
      evade the host immune defenses. Whether or not immunization with the p28 of one
      strain of E. chaffeensis would confer cross-protection against other strains
      needs to be investigated.

PMID- 10074539
TI  - Rapid film-based determination of antibiotic susceptibilities of Mycobacterium
      tuberculosis strains by using a luciferase reporter phage and the Bronx Box.
AB  - Detecting antibiotic resistance in Mycobacterium tuberculosis is becoming
      increasingly important with the global recognition of drug-resistant strains and
      their adverse impact on clinical outcomes. Current methods of susceptibility
      testing are either time-consuming or costly; rapid, reliable, simple, and
      inexpensive methods would be highly desirable, especially in the developing world
      where most tuberculosis is found. The luciferase reporter phage is a unique
      reagent well-suited for this purpose: upon infection with viable mycobacteria, it
      produces quantifiable light which is not observed in mycobacterial cells treated
      with active antimicrobials. In this report, we describe a modification of our
      original assay, which allows detection of the emitted light with a Polaroid film
      box designated the Bronx Box. The technique has been applied to 25 M.
      tuberculosis reference and clinical strains, and criteria are presented which
      allow rapid and simple discrimination among strains susceptible or resistant to
      isoniazid and rifampin, the major antituberculosis agents.

PMID- 10074540
TI  - Human herpesvirus 8 seroprevalence and evaluation of nonsexual transmission
      routes by detection of DNA in clinical specimens from human immunodeficiency
      virus-seronegative patients from central and southern Italy, with and without
      Kaposi's sarcoma.
AB  - In order to investigate the seroprevalence of human herpesvirus 8 (HHV-8)
      infection in central and southern Italy, sera from human immunodeficiency virus
      (HIV)-seronegative subjects, with and without Kaposi's sarcoma (KS), were
      analyzed by immunofluorescence assay, using BC-3, a cell line latently infected
      with HHV-8. High titers of antibody against HHV-8 lytic and latent antigens were
      detected in all 50 KS patients studied, while in 50 HIV-seronegative subjects
      without KS, 32 (64%) were found positive for HHV-8 antibodies. Titers in the sera
      of these patients were lower than those for KS patients. This data suggests that
      HHV-8 infection is not restricted to KS patients and that the prevalence of HHV-8
      infection in the general population may be correlated with differing rates of
      prevalence of KS in different parts of the world. In view of these findings,
      possible nonsexual transmission routes were evaluated. Nested PCR was used to
      test for the presence of HHV-8 DNA in saliva, urine, and tonsillar swabs from KS
      and non-KS patients. In KS patients, 14 out of 32 tonsillar swabs (43.7%), 11 out
      of 24 saliva samples (45.8%), and just 2 out of 24 urine samples (8.3%) tested
      positive for HHV-8 DNA. In the control group, on the contrary, none of the 20
      saliva and 20 urine specimens was positive for HHV-8 DNA; only 1 out of 22
      tonsillar swabs gave a positive result. This data supports the hypothesis that
      HHV-8 infects the general population in a latent form. The reactivation of viral
      infection may result in salivary shedding of HHV-8, contributing to viral spread
      by nonsexual transmission routes.

PMID- 10074541
TI  - Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow
      transplant patient: species identification and review of the literature.
AB  - Trichoderma longibrachiatum was recovered from stool surveillance cultures and a
      perirectal ulcer biopsy specimen from a 29-year-old male who had received an
      allogeneic bone marrow transplant for acute lymphoblastic leukemia. The
      amphotericin B (2.0 microgram/ml) and itraconazole (1.0 microgram/ml) MICs for
      the organism were elevated. Therapy with these agents was unsuccessful, and the
      patient died on day 58 posttransplantation. At autopsy, histologic sections from
      the lungs, liver, brain, and intestinal wall showed infiltration by branching
      septate hyphae. Cultures were positive for Trichoderma longibrachiatum. While
      Trichoderma species have been recognized to be pathogenic in profoundly
      immunosuppressed hosts with increasing frequency, this is the first report of
      probable acquisition through the gastrointestinal tract. Salient features
      regarding the identification of molds in the Trichoderma longibrachiatum species
      aggregate are presented.

PMID- 10074542
TI  - Facklamia languida sp. nov., isolated from human clinical specimens.
AB  - Three strains of a gram-positive catalase-negative, facultatively anaerobic
      coccus-shaped organism originating from human clinical samples were characterized
      by phenotypic and molecular taxonomic methods. Sequencing of genes encoding 16S
      rRNA showed that the strains are phylogenetically closely related (99.9 to 100%
      sequence similarity) and represent a new subline within the genus Facklamia. The
      unknown bacterium was readily distinguished from all currently described species
      of the genus Facklamia (viz., Facklamia hominis, Facklamia ignava, and Facklamia
      sourekii) by biochemical tests and electrophoretic analysis of whole-cell
      proteins. Based on phylogenetic and phenotypic evidence, it is proposed that the
      unknown bacterium be classified as Facklamia languida sp. nov. The type strain of
      F. languida is CCUG 37842.

PMID- 10074543
TI  - Immunohistochemical detection of JC virus in nontumorous renal tissue of a
      patient with renal cancer but without progressive multifocal leukoencephalopathy.
AB  - We performed immunohistochemical staining on the nontumorous renal tissue of 45
      patients with renal cancer but without progressive multifocal encephalopathy
      using JCV-specific antibody. For one patient we found positive staining of the
      nuclei of the renal collecting ducts. Immunoelectron microscopic examination of
      the positive cell nuclei revealed electron-dense polyomavirus-like particles.

PMID- 10074544
TI  - Serological evidence of infection with Ehrlichia spp. in red foxes (Vulpes
      vulpes) in Switzerland.
AB  - Serum samples from 1,550 red foxes in Switzerland were tested for antibodies to
      the agents of canine granulocytic and monocytic ehrlichiosis by an indirect
      immunofluorescent technique. Forty-four (2.8%) of the samples were positive for
      Ehrlichia phagocytophila, which is an antigen marker for granulocytic
      ehrlichiosis. In contrast, none of the samples had antibodies specific to
      Ehrlichia canis, the agent of monocytic ehrlichiosis.

PMID- 10074545
TI  - Serotyping of Cryptococcus neoformans isolates from clinical and environmental
      sources in Spain.
AB  - We determined biovars and serotypes of 154 isolates of Cryptococcus neoformans
      from clinical and environmental sources from different areas of Spain. All
      clinical isolates belonged to C. neoformans var. neoformans. Serotypes showed an
      irregular distribution. C. neoformans var. gattii serotype B was isolated from
      necropsy specimens from goats with pulmonary disease.

PMID- 10074546
TI  - Identification of Vibrio parahaemolyticus strains at the species level by PCR
      targeted to the toxR gene.
AB  - The DNA colony hybridization test with the polynucleotide probe for Vibrio
      parahaemolyticus toxR gene was performed. All 373 strains of V. parahaemolyticus
      gave positive results, and the strains belonging to four other Vibrio species
      including Vibrio alginolyticus gave weakly positive results, suggesting that toxR
      sequence variation may reflect the phylogenetic relationships of Vibrio species.
      We then established a toxR-targeted PCR protocol for the specific detection of V.
      parahaemolyticus.

PMID- 10074547
TI  - Use of an oxacillin disk screening test for detection of penicillin- and
      ceftriaxone-resistant pneumococci.
AB  - In a context of worldwide emergence of resistance among Streptococcus pneumoniae
      strains, early detection of strains with decreased susceptibility to beta-lactam
      antibiotics is important for clinicians. If the 1-microgram oxacillin disk
      diffusion test is used as described by the National Committee for Clinical
      Laboratory Standards, no interpretation is available for strains showing zone
      sizes of </=19 mm, and there is presently no disk diffusion test available for
      screening cephalosporin resistance. The zones obtained by the diffusion method by
      using the 1-microgram oxacillin disk were compared with penicillin MICs for 1,116
      clinical strains and with ceftriaxone MICs for 695 of these strains. Among the
      342 strains with growth up to the 1-microgram oxacillin disk margin, none were
      susceptible (MIC, </=0.06 microgram/ml), 62 had intermediate resistance (MIC,
      0.12 to 1.0 microgram/ml), and 280 were resistant (MIC, >/=2.0 microgram/ml) to
      penicillin. For ceftriaxone, among 98 strains with no zone of inhibition in
      response to oxacillin, 68 had intermediate resistance (MIC, 1.0 microgram/ml),
      and 22 were resistant (MIC, >/=2.0 microgram/ml). To optimize the use of the disk
      diffusion method, we propose that the absence of a zone of inhibition around the
      1-microgram oxacillin disk be regarded as an indicator of nonsusceptibility to
      penicillin and ceftriaxone and recommend that such strains be reported as
      nonsusceptible to these antimicrobial agents, pending the results of a MIC
      quantitation method.

PMID- 10074548
TI  - Evidence for nasal carriage of methicillin-resistant staphylococci colonizing
      intravascular devices.
AB  - Nasal surveillance cultures were performed for 54 patients exhibiting >/=10(3)
      CFU of methicillin-resistant coagulase-negative staphylococci per ml in central
      venous catheter (CVC) rinse cultures over a 6-month period. Forty-two of the
      nasal cultures yielded growth of methicillin-resistant coagulase-negative
      staphylococci, and 33 of the 42 cultures contained organisms that belonged to the
      same species as the CVC isolates. Of the 33 same-species isolates, 20 appeared to
      be identical strains by pulsed-field gel electrophoresis analysis. These data
      suggest that measures should be taken to reduce cross-contamination between the
      respiratory tract and intravascular devices. However, the potential interest in
      detecting methicillin-resistant coagulase-negative staphylococcus carriage in
      high-risk patients is hampered by the lack of sensitivity of nasal surveillance
      cultures.

PMID- 10074549
TI  - Aspergillus meningitis: diagnosis by non-culture-based microbiological methods
      and management.
AB  - The performance of antibody detection, antigen detection, and Aspergillus genus
      specific PCR for diagnosing Aspergillus meningitis was investigated with 26
      cerebrospinal fluid (CSF) samples obtained from a single patient with proven
      infection caused by Aspergillus fumigatus. Immunoglobulin G antibodies directed
      against Aspergillus were not detected by enzyme-linked immunosorbent assay in CSF
      or serum. The antigen galactomannan was detected in the CSF 45 days before a
      culture became positive, and Aspergillus DNA was detected 4 days prior to
      culture. Decline of the galactomannan antigen titer in the CSF during treatment
      with intravenous and intraventricular amphotericin B and intravenous voriconazole
      corresponded with the clinical response to treatment.

PMID- 10074550
TI  - Rapid identification of Staphylococcus aureus by using fluorescent
      staphylocoagulase assays.
AB  - Two rapid (1-h) assays for the detection of Staphylococcus aureus
      staphylocoagulase were developed by using the fluorogenic thrombin substrates N-t
      boc-Val-Pro-Arg-7-amido-4-methylcoumarin (VPA) and N-t-boc-beta-benzyl-Asp-Pro
      Arg-7-amido-4-methylocoumarin (BB). The assays were compared to the tube
      coagulase test and latex agglutination (LA) (Sanofi Diagnostics Pasteur,
      Guildford, Surrey, United Kingdom) by using 406 clinical isolates of
      staphylococci, and they produced positive and negative predictive values of 99.2
      and 99. 1% for LA, 98.9 and 92.7% for VPA, and 98.9 and 99.1% for BB. Fluorescent
      assays used colonies from solid media, thereby eliminating the need for broth
      cultures, and were performed in microtiter trays, thus making them suitable for
      large-scale screening.

PMID- 10074551
TI  - Central line sepsis in a child due to a previously unidentified mycobacterium.
AB  - A rapidly growing mycobacterium similar to strains in the present Mycobacterium
      fortuitum complex (M. fortuitum, M. peregrinum, and M. fortuitum third biovariant
      complex [sorbitol positive and sorbitol negative]) was isolated from a surgically
      placed central venous catheter tip and three cultures of blood from a 2-year-old
      child diagnosed with metastatic hepatoblastoma. The organism's unique phenotypic
      profile and ribotype patterns differed from those of the type and reference
      strains of the M. fortuitum complex and indicate that this organism may represent
      a new pathogenic taxon.

PMID- 10074552
TI  - rpoB mutations in multidrug-resistant strains of Mycobacterium tuberculosis
      isolated in Italy.
AB  - Mutations of rpoB associated with rifampin resistance were studied in 37
      multidrug-resistant (MDR) clinical strains of Mycobacterium tuberculosis isolated
      in Italy. At least one mutated codon was found in each MDR strain. It was always
      a single-base substitution leading to an amino acid change. Nine different rpoB
      alleles, three of which had not been reported before, were found. The relative
      frequencies of specific mutations in this sample were different from those
      previously reported from different geographical areas, since 22 strains (59.5%)
      carried the mutated codon TTG in position 531 (Ser-->Leu) and 11 (29.7%) had GAC
      in position 526 (His-->Asp).

PMID- 10074553
TI  - Contaminations occurring in fungal PCR assays.
AB  - Successful in vitro amplification of fungal DNA in clinical specimens has been
      reported recently. In a collaboration among five European centers, the frequency
      and risk of contamination due to airborne spore inoculation or carryover
      contamination in fungal PCR were analyzed. The identities of all contaminants
      were specified by cycle sequencing and GenBank analysis. Twelve of 150 PCR assays
      that together included over 2,800 samples were found to be contaminated (3.3% of
      the negative controls were contaminated during the DNA extraction, and 4.7% of
      the PCR mixtures were contaminated during the amplification process).
      Contaminants were specified as Aspergillus fumigatus, Saccharomyces cerevisiae,
      and Acremonium spp. Further analysis showed that commercially available products
      like zymolyase powder or 10x PCR buffer may contain fungal DNA. In conclusion,
      the risk of contamination is not higher in fungal PCR assays than in other
      diagnostic PCR-based assays if general precautions are taken.

PMID- 10074554
TI  - Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South
      Africa: rarity of the vacA s1a genotype and natural occurrence of an s2/m1
      allele.
AB  - We describe the rarity of Helicobacter pylori strains of vacuolating cytotoxin
      type s1a (the type most commonly associated with peptic ulceration in the United
      States) among black and mixed-race South Africans. We also provide the first
      description of a naturally occurring strain with the vacA allelic structure
      s2/m1.

PMID- 10074555
TI  - Comparison of the MB/BacT and BACTEC 460 TB systems for recovery of mycobacteria
      from various clinical specimens.
AB  - A total of 1,830 specimens (75.7% respiratory and 24.3% nonrespiratory) were
      cultured in parallel with the MB/BacT and BACTEC 460 TB systems and on Lowenstein
      Jensen (LJ) medium. Mycobacteria were identified from 173 (6.5%) specimens. The
      most common species recovered were Mycobacterium tuberculosis complex (65. 9%),
      Mycobacterium avium complex (22.5%), and Mycobacterium chelonae (9.2%). The
      recovery rates by individual systems were 96.5, 99.4, and 95.9% for MB/BacT,
      BACTEC 460 TB, and LJ medium, respectively, for all mycobacteria; the recovery
      rates were 99.1, 100, and 98.2%, respectively, for M. tuberculosis complex alone.
      The difference among the recovery rates for all mycobacteria and those for
      individual species was not significant. The BACTEC 460 TB system detected M.
      tuberculosis isolates more rapidly than the MB/BacT system (8 versus 11.8 days
      for smear-positive specimens [P < 0.01] and 18 versus 21 days for smear-negative
      specimens [P < 0.05]), whereas the MB/BacT system more rapidly detected the
      nontuberculous mycobacteria (17.1 versus 12.7 days [P < 0.01]). These results
      indicate that the nonradiometric MB/BacT system is a rapid, sensitive, and
      efficient method for the recovery of M. tuberculosis and nontuberculous
      mycobacteria from both pulmonary and extrapulmonary clinical specimens.

PMID- 10074556
TI  - Comparison of levels of human immunodeficiency virus type 1 RNA in plasma as
      measured by the NucliSens nucleic acid sequence-based amplification and
      Quantiplex branched-DNA assays.
AB  - This study compared levels of human immunodeficiency virus type 1 RNA in plasma
      as measured by the Quantiplex branched-DNA and NucliSens nucleic acid sequence
      based amplification assays. RNA was detectable in 118 of 184 samples (64.13%) by
      the Quantiplex assay and in 171 of 184 samples (92.94%) by the NucliSens assay.
      Regression analysis indicated that a linear relationship existed between the two
      sets of values (P < 0.0001), although the Quantiplex and NucliSens values were
      significantly different (P < 0.001), with the NucliSens values being
      approximately 0.323 log higher. Spearman correlation analysis indicated that the
      overall changes in patient viral load patterns were highly correlative between
      the two assays: r = 0.912, P < 0.0001. The lower limits of sensitivity were
      determined to be approximately 100 copies/ml and 1,200 to 1,400 copies/ml for the
      NucliSens and Quantiplex assays, respectively.

PMID- 10074557
TI  - Isolation of a human rotavirus strain with a super-short RNA pattern and a new P2
      subtype.
AB  - Super-short rotavirus strains that have a rearranged gene segment 11 are rarely
      found in humans, and only five isolates, all from Southeast Asia, have been
      described in the literature. We report the first isolation in Japan from an
      infant with severe diarrhea of a rotavirus possessing a super-short RNA pattern.
      This strain, designated AU19, had a G1 VP7 and is also the first isolate in Japan
      that possesses a P2[6] VP4. Furthermore, the P2[6] VP4 carried by AU19 was
      divergent in the hypervariable region of the amino acid sequence from the P2A[6]
      VP4s carried by asymptomatic neonatal strains or from the P2B[6] VP4 carried by
      porcine rotavirus strain Gottfried. Thus, AU19 is likely to represent a new VP4
      subtype, which we propose to call P2C. Given the recent emergence of the P2[6]
      VP4s in India, Brazil, and the United States and the role of VP4 in protective
      immunity, further scrutiny is justified to see whether the emergence of the
      previously underrepresented P2[6] VP4 serotype is related to this new P2 subtype.

PMID- 10074558
TI  - Identification of a novel genotype of hepatitis G virus in Southeast Asia.
AB  - Hepatitis G virus (HGV) isolates obtained from 20 Myanmarese and 10 Vietnamese
      subjects were analyzed. A cluster of isolates not belonging to any known genotype
      of HGV was found in five Myanmarese subjects and three Vietnamese subjects by
      phylogenetic analysis, and we classified this new genotype as type 4. These
      results revealed that the HGV genome can be classified into at least four major
      genotypes.

PMID- 10074559
TI  - Production of specific monoclonal antibodies to Aspergillus species and their use
      in immunohistochemical identification of aspergillosis.
AB  - Two anti-Aspergillus murine monoclonal antibodies (MAbs), designated 164G and
      611F, have been produced; both specifically recognize cytoplasmic antigens of A.
      fumigatus, A. flavus, and A. niger by enzyme-linked immunosorbent assay. The MAbs
      can identify Aspergillus spp. both in frozen sections by immunofluorescence and
      in paraffin-embedded clinical specimens by immunofluorescence and
      immunoperoxidase staining.

PMID- 10074560
TI  - Specificity of IS6110-based DNA fingerprinting and diagnostic techniques for
      Mycobacterium tuberculosis complex.
AB  - Restriction fragment length polymorphism and hybridization of DNA extracted from
      Mycobacterium tuberculosis, nontuberculous mycobacteria, and nonmycobacterial
      species with a probe derived from IS6110 confirmed that IS6110 was specific to M.
      tuberculosis complex. In addition, DNA amplification with IS6110-specific primers
      yielded a 181-bp fragment only in DNA from M. tuberculosis complex isolates.

PMID- 10074561
TI  - Case of sepsis caused by Bifidobacterium longum.
AB  - We report a case of sepsis caused by Bifidobacterium longum in a 19-year-old male
      who had developed high fever, jaundice, and hepatomegaly after acupuncture
      therapy with small gold needles. Anaerobic, non-spore-forming, gram-positive
      bacilli were isolated from his blood and finally identified as B. longum. He
      recovered completely after treatment with ticarcillin and metronidazole. To our
      knowledge, this is the first report of incidental sepsis caused by B. longum.

PMID- 10074562
TI  - Lazaroid U74389G ameliorates ischemia-reperfusion injury in the rat lung
      transplant model.
AB  - We investigated the effect of Lazaroid U74389G on ischemia-reperfusion injury in
      the rat orthotopic left lung transplantation model. Five groups of reperfused
      lungs were studied. In group I, donor lungs were transplanted after 12 hours of
      preservation in University of Wisconsin (UW) solution at 4C. In groups II, III,
      and IV, Lazaroid was intravenously administrated at a dose of 1 mg/kg, 8 mg/kg,
      and 15 mg/kg, respectively, to the donors 30 minutes before preservation and also
      to the recipients 30 minutes before reperfusion after 12 hours of storage in UW
      solution at 4C. In group V, Lazaroid was added to the UW solution (80
      micromol/l), and also was administered intravenously (6 mg/kg) 30 minutes before
      reperfusion. After 1 hour of reperfusion, gas exchange function and tissue lipid
      peroxide levels were significantly improved in Lazaroid-treated groups III, and V
      compared with no treatment group I. Histologic damage was less severe in groups
      III, IV, and V than in group I. These findings suggest that Lazaroid U74389G
      ameliorates ischemia-reperfusion injury in the rat lung transplants by inhibiting
      lipid peroxidation, regardless of whether it is administrated intravenously or
      given as an additive to the preservation solution.

PMID- 10074563
TI  - Video-assisted thoracoscopic thymectomy.
AB  - Video-assisted thoracoscopic surgery (VATS) provides a new, alternative approach
      to thymectomy and has several advantages over the other established techniques.
      However, even among surgeons using this approach, there are differences in the
      actual technique. We prefer the right approach using conventional instruments.
      The rationale behind our technique is discussed.

PMID- 10074564
TI  - Efficacy of initial controlled perfusion pressure for ischemia-reperfusion injury
      in a 24-hour preserved lung.
AB  - In lung transplantation, the safety period of the ischemic time of the graft is
      within 6 hours. Because of the problem of donor shortage, it is essential to
      extend the safety period of the preservation time of the donor lung. However, the
      longer the preservation time is, the more severe is the resulting ischemia
      reperfusion injury. This study was designed to evaluate the efficacy of initial
      controlled perfusion pressure in the reduction of ischemia-reperfusion injury in
      a 24-hour preserved lung. Japanese white rabbit lungs were flushed with a low
      potassium dextran solution (4C, 500 ml) after injection of prostaglandin E1 (20
      microgram, bolus via PA) and submersed in the same solution for 24 hours at 4C.
      After preservation, the left lung was reperfused using an extracorporeal lung
      perfusion model which comprised of a closed circuit combined with a membrane
      deoxygenator. Assessment of lung function included gas analysis of influent and
      effluent blood and mean pulmonary artery perfusion pressure. Then the lung
      wet/dry weight ratio was calculated. In group I of the control group (n=6), the
      left lung was reperfused immediately following flushing (without preservation) at
      a flow rate of 50 ml/min for 60 minutes. In groups II and III, grafts were stored
      for 24 hours. In group II, grafts (n=6) were reperfused at a flow rate of 50
      ml/min for 60 minutes. In group III (n =6), the flow rate was controlled by
      maintaining the perfusion pressure below 30 mmHg during the initial 5 minutes and
      was increased to 50 ml/min for the subsequent 60 minutes. In group II, the mean
      pulmonary artery pressure during perfusion increased rapidly, and oxygenation
      deteriorated. All grafts developed pulmonary edema within 12 minutes after
      reperfusion. Examination of the specimen revealed that the peripheral lung was
      not perfused. In group III, the mean pulmonary artery perfusion pressure was
      maintained below 30 mmHg, and oxygenation was preserved sufficiently throughout
      the experiment (delta PO2 > 100 mmHg) with no significant difference from control
      values. In conclusion, ischemia-reperfusion injury of the 24-hour preserved lung
      was attenuated prominently by controlling initial perfusion pressure for 5
      minutes.

PMID- 10074565
TI  - Recovery from metabolic impairments after hypothermic cardiopulmonary bypass:
      postoperative changes in arterial-venous carbon dioxide tension difference.
AB  - Arterial-venous carbon dioxide tension differences (Pv-aCO2) are known to
      increase during the resuscitation phase following several types of shock. We
      hypothesized that Pv-aCO2 increases immediately following hypothermic
      cardiopulmonary bypass (CPB) because of the metabolic impairments that occur
      during CPB. Fifty-six adult patients underwent hypothermic CPB for cardiac
      surgery. Arterial and mixed venous blood gases were analyzed every 6 hours for
      the first 24 hours following cardiac surgery. Immediately after surgery, the Pv
      aCO2 was elevated (8.2 +/- 2.9 mmHg), but gradually returned to a normal range
      within 12 hours (6.2 +/- 3.2 mmHg, p < 0.001). Factors (X) which correlated
      significantly with the postoperative Pv-aCO2 (Y) included the minimum rectal
      temperature during CPB (Y= 27.3 - 0.664X, p = 0.011) and the duration of CPB (Y=
      5.6 + 0.0172X, p = 0.047). The abnormally high Pv-aCO2 during the early
      postoperative period may be caused by metabolic impairments during hypothermic
      CPB. The recovery stage following open heart surgery is therefore similar to the
      resuscitation phase after shock.

PMID- 10074566
TI  - Myocardial revascularization without cardiopulmonary bypass in patients with
      operative risk factors.
AB  - We have treated 7 myocardial revascularization cases with operative risk factors,
      using the beating heart technique without cardiopulmonary bypass. Operative risk
      factors included left ventricular dysfunction, calcified aorta, chronic renal
      failure, cerebrovascular accident, immunosupressive state and old age. The 6
      males and 1 female ranged in age from 54 to 84 years (mean age 70 years). The
      mean number of grafts was 1.3 per patient. All were extubated within 3 hours of
      arrival at the intensive care unit. Inotropic catecholamin support was not
      necessary on postoperative days. None of our patients had perioperative
      myocardial infarction. Postoperative angiography showed that all grafts were
      patent. We have found, based on our experiences, that selected patients can
      safely undergo CABG without cardiopulmonary support.

PMID- 10074567
TI  - Minimally invasive "pocket incision" aortic valve surgery.
AB  - A minimally invasive approach to aortic valve surgery through a transverse
      incision ("pocket incision") at the right second intercostal space was examined.
      Sixteen patients with a mean age of 30 years underwent this approach. The third
      costal cartilage was either excised (n = 5) or dislocated (n = 11). The right
      internal mammary artery was preserved. Cardiopulmonary bypass (CPB) was
      established with aortic-right atrial cannulation in all except the first case.
      Aortic valve replacements (AVR) were performed in 15 patients and one had aortic
      valve repair with concomitant ventricular septal defect closure. There was no
      mortality and no major complications. The aortic cross-clamp, CPB and operative
      times were 72 +/- 19 mins, 105 +/- 26 mins and 3 hrs 00 min +/- 29 mins
      respectively. The mean time to extubation was 5.7 +/- 4.0 hrs, ICU stay of 27 +/-
      9 hrs and postoperative hospital stay of 5.1 +/- 1.2 days. Minimally invasive
      "pocket incision" aortic valve surgery is technically feasible and safe. It has
      the advantages of central cannulation for CPB, preservation of the internal
      mammary artery and avoiding sternotomy. This approach is cosmetically acceptable
      and allows rapid patient recovery.

PMID- 10074568
TI  - The effect of direct lidocaine injection into the clamped aortic segment on the
      spinal evoked potential: early diagnosis for spinal cord ischemia.
AB  - PURPOSE: The aim of this study was to identify a method to determine whether
      segmental artery reconstruction was indicated during aortic clamping. METHOD:
      Spinal cord evoked potential (SCEP) and regional spinal blood flow were studied
      in 24 adult dogs. Using the left heart bypass technique, aortic clamping divided
      the aorta into thoracic, abdominal, and terminal segments. After the occlusion of
      the descending aorta and discontinuation of the perfusion to the abdominal
      segment, animals were assigned to four groups: no treatment with perfusion to the
      terminal aorta (group IA), no treatment with cessation of bypass (group IB), 5%
      lidocaine administration (5 mg/kg) into the abdominal segment with perfusion to
      the terminal aorta (group IIA), and lidocaine administration with cessation of
      bypass (group IIB). RESULTS: Cessation of bypass reduced spinal blood flow and
      SCEP amplitude. Lidocaine injection allowed for a significant rapid decrease in
      SCEP amplitude in group IIB compared with group IB (24.2% +/- 13.4% versus 92.3%
      +/- 33.2%; p = 0.0039). The degree of spinal blood supply was reflected
      immediately in the magnitude of SCEP amplitude change by the direct lidocaine
      injection. (group IB versus group IIB; p = 0.023). CONCLUSION: The direct
      injection of lidocaine into the clamped aorta results in a rapidly change in SCEP
      in the threat of ischemia and can be used to make an early detection of the
      segmental arteries perfusing to the spinal cord.

PMID- 10074569
TI  - Successful use of high frequency oscillatory ventilation for pneumomediastinum.
AB  - An infant with pneumomediastinum due to mechanical ventilation was successfully
      treated using high frequency oscillatory ventilation (HFOV). The 3-month-old male
      had undergone ligation of a patent ductus arteriosus and suffered from
      barotraumatic pneumomediastinum in the postoperative period. Computed tomography
      of the chest confirmed the diagnosis. While using conventional mechanical
      ventilation the respiratory failure worsened. HFOV was instituted and the patient
      improved. A lower airway pressure by this mode of ventilation provided
      significant advantages in the patient with an air leak. He was subsequently
      extubated and discharged home.

PMID- 10074570
TI  - Spontaneous recanalization of postoperative severe graft stenosis. What is the
      cause and prognosis of the "string sign" in the internal thoracic artery?
AB  - A 68-year-old female with unstable angina was treated surgically. She was
      referred to the surgical ward by cardiologists because of a diagnosis of unstable
      angina with three vessel disease. On a coronary angiogram (CAG), 90% stenoses
      were found in the left anterior descending coronary artery (LAD), circumflex
      (CX), and right coronary artery (RCA). She received elective coronary artery
      bypass grafting (CABG), in which the left internal thoracic artery (LITA) was
      anastomosed to the LAD and reversed saphenous vein grafts (SVG) were made to
      segment 12 of the CX, and segment 4PD of the RCA, respectively. The postoperative
      course was uneventful, but postoperative early graftgraphy revealed distal
      narrowing of the LITA graft as the so-called "string sign". However, one year
      post surgery, the LITA string sign was not found and its patency had markedly
      improved on the second graftgram. It is reported that the LITA "string sign"
      might cause late graft occlusion. However, this LITA graft evidently enlarged the
      size and increased the flow of the artery in proportion to myocardial blood
      demand. To our knowledge, it has not been reported that an in situ LITA string
      sign on postoperative early graftgram has disappeared in the late phase. We
      hypothesize that the LITA string sign might be caused by several different
      factors such as flow competition, spasm, and/or technical problems. In any event,
      the LITA string sign does not cause graft occlusion in the late postoperative
      period in every case.

PMID- 10074571
TI  - A new devised skirted elephant trunk technique.
AB  - A simple and effective new elephant trunk technique was devised and applied to
      two patients with a successful result. In advance before the operation, an arch
      graft with a skirted elephant trunk was made. This was done by inserting a
      smaller, 22 mm diameter sized graft into the arch graft at the distal end and
      suturing it so as to leave a skirt extending over the smaller graft. This
      configuration facilitates the distal anastomosis and effectively shortens
      anastomotic time.

PMID- 10074572
TI  - Ruptured distal aortic arch aneurysm associated with arteriosclerosis obliterans.
AB  - A 73-year-old man with a ruptured distal aortic arch aneurysm into the
      pericardial space, mediastinum and right pleural space is described. The patient
      underwent a successful total aortic arch replacement using deep hypothermia,
      systemic circulatory arrest and selective cerebral perfusion. Extracorporeal
      circulation was established with right axillar arterial perfusion due to
      arteriosclerosis obliterans (ASO). Presentation and management are discussed.

PMID- 10074573
TI  - Single-stage surgery for distal aortic arch aneurysm and infrarenal abdominal
      aortic aneurysm through anterolateral approach.
AB  - A 58-year-old man with a distal aortic arch aneurysm (DAA) associated with an
      infrarenal abdominal aortic aneurysm (AAA) successfully underwent a single-stage
      replacement of the aneurysms. A left anterolateral thoracotomy was used for
      replacement of the DAA, which was performed using profound hypothermic
      circulatory arrest and continuous retrograde cerebral perfusion. An
      extraperitoneal approach in conjunction with a lateral abdominal incision was
      employed for replacement of the AAA. The combination of an anterolateral
      thoracotomy and a lateral abdominal incision is useful in combined surgery for
      DAA and AAA.

PMID- 10074575
TI  - "True" mycotic aneurysm of a renal artery allograft.
AB  - A 60-year-old white man sustained a rupture of the renal artery 6 weeks after a
      cadaveric kidney transplantation. The bleeding site was repaired, and culture of
      the hematoma showed an isolated growth of Candida albicans. Blood and urine
      cultures were negative. Systemic antifungal therapy was initiated. Bleeding from
      the renal artery recurred, eventually requiring removal of the transplanted
      kidney. Histopathology of the resected specimen showed budding yeast in the wall
      of the renal artery, but no evidence of fungal invasion of the kidney. The
      patient received 6 weeks of amphotericin B therapy and currently remains on
      hemodialysis therapy.

PMID- 10074574
TI  - Auditory perception: does practice make perfect?
AB  - Recent studies have shown that adult humans can learn to localize sounds
      relatively accurately when provided with altered localization cues. These
      experiments provide further evidence for experience-dependent plasticity in the
      mature brain.

PMID- 10074577
TI  - Recurrence of focal segmental glomerulosclerosis associated with Kimura's disease
      after kidney transplantation.
AB  - A 13-year-old Brazilian boy with Kimura's disease (eosinophylic lymphoid
      granuloma) and nephrotic syndrome is reported. Native kidney biopsy showed focal
      segmental glomerulosclerosis (FSGS). Treatment with prednisolone resulted in
      partial remission of proteinuria, and he had a progressive loss in renal
      function, requiring initiation of chronic dialysis, which he underwent for 46
      months. After kidney transplantation, the patient developed proteinuria. A renal
      biopsy showed recurrence of focal segmental glomerulosclerosis, and subsequently
      he developed renal insufficiency.

PMID- 10074578
TI  - Fatal cardiac beta2-microglobulin amyloidosis in patients on long-term
      hemodialysis.
AB  - We report two long-term hemodialysis patients who developed severe congestive
      heart failure attributable to cardiac heavy amyloid deposition. Both patients
      became hypotensive during dialysis sessions, gradually making it difficult to
      continue hemodialysis, and they died of congestive heart failure. At autopsy,
      left ventricle walls in each case contained diffuse extensive deposits of
      amyloid. The distribution of amyloid was not localized to vessel walls but was
      widely disseminated throughout the left ventricle walls and replaced myocardial
      muscle fibers. Immunohistochemical examination showed positive staining for anti
      human beta2-microglobulin antibody. We conclude that cardiac dialysis-related
      amyloidosis should also be considered in long-term hemodialysis patients with
      congestive heart failure as a life-threatening complication.

PMID- 10074579
TI  - POEMS syndrome, steroid-dependent diabetes mellitus, erythema elevatum diutinum,
      and rheumatoid arthritis as extramedullary manifestations of plasma cell
      dyscrasia.
AB  - POEMS syndrome is a rare synopsis of different multisystemic disorders
      (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy, and skin
      lesions) associated with plasma cell dyscrasia. We herein report the atypical
      case of a 44-year-old white man presenting with glomerulopathy, POEMS syndrome,
      and erythema elevatum diutinum with a few-year history of non-insulin-dependent
      diabetes mellitus (NIDDM) and seronegative rheumatoid arthritis (RA) as early
      manifestations of IgAlambda multiple myeloma. The prescription of 1 mg/kg/day
      prednisone improved the patient's features dramatically. Skin lesions improved by
      the association of glucocorticoids and plasma exchange, recurred when
      plasmapheresis ceased, and remitted when plasma exchange was reintroduced. NIDDM
      requiring insulinotherapy recurred when corticoids were discontinued and remitted
      when prednisone was reintroduced. However, prednisone and plasmapheresis had no
      effect on polyneuropathy, M-paraprotein, and plasma cell dyscrasia in our
      patient, who developed indolent multiple myeloma a few years later. We thus
      concluded that POEMS syndrome, steroid-dependent diabetes mellitus, rheumatoid
      arthritis, RA, and skin vasculitis in our patient were triggered by plasma cell
      dyscrasia.

PMID- 10074580
TI  - Pseudotumor cerebri: an unusual complication of brachiocephalic vein thrombosis
      associated with hemodialysis catheters.
AB  - We report a case of pseudotumor cerebri (PC) in a maintenance hemodialysis
      patient that was associated with thrombosis of the right and left brachiocephalic
      veins caused by repeated subclavian and jugular vein catheterizations. Symptoms
      and signs of PC appeared when a right forearm Gortex graft was inserted. PC
      secondary to intracranial venous outflow obstruction is an important diagnostic
      consideration for hemodialysis patients with headache, visual disturbance, and
      papilledema.

PMID- 10074581
TI  - Fibrillary glomerulonephritis in siblings.
AB  - Fibrillary/immunotactoid glomerulopathy is characterized by organized glomerular
      deposition of extracellular, nonbranching, immunoglobulin-derived microfibrils,
      which is not associated with systemic diseases such as amyloidosis,
      cryoglobulinemia, or monoclonal gammopathy. This is an uncommon condition with an
      obscure etiology and accounts for approximately 1% of primary glomerular diseases
      in white populations. We report the first case of familial
      fibrillary/immunotactoid glomerulopathy affecting a brother and a sister in a
      Chinese family. Both patients presented with heavy proteinuria, which improved
      transiently on treatment with prednisolone and cyclophosphamide. Human lymphocyte
      antigen typing for the siblings showed no haplotype association. Despite the
      generally poor renal prognosis reported in the literature, with 50% of patients
      reaching end-stage renal failure within 2 to 4 years, both patients had relative
      preservation of renal function (creatinine clearance from 79 to 76 mL/min/1.73 m2
      after 2 years in one patient and from 111 to 99 mL/min/1.73 m2 after 3 years in
      the other). Our observations show that fibrillary/immunotactoid glomerulopathy
      can present as a familial condition. Compared with sporadic cases, patients with
      familial fibrillary/immunotactoid glomerulopathy may have a more favorable renal
      prognosis.

PMID- 10074583
TI  - Familial lobular glomerulopathy: first case report in Asia.
AB  - A 23-year-old male Japanese student presented a unique lobular glomerulopathy
      characterized by mesangial and subendothelial expansion with numerous periodic
      acid-Schiff-positive deposits. Electron microscopy showed massive fine granular
      deposits with a homogeneous distribution. Fibrillar or microtubular structures
      were not demonstrated. Fibronectin was positive on immunostaining, as was
      immunoglobulin G and fibrinogen. Familial study revealed that the patient's
      grandfather, two aunts, and one cousin on his father's side had developed end
      stage renal failure. Clinicopathologic features of this patient are identical
      with those of familial lobular glomerulopathy, which has been previously
      described by several investigators. Seven of the previously reported families
      were white and resided in the United States or in European countries. This is the
      first report of an Asian case, and indicates that this disease universally occurs
      independently of racial specificity.

PMID- 10074584
TI  - Molecular genetic and immunohistochemical study of autosomal recessive Alport's
      syndrome.
AB  - A DNA analysis of autosomal type IV collagen alpha3 and alpha4 chain genes
      (COL4A3 and COL4A4) and an immunohistochemical study of type IV collagen alpha1
      to alpha6 chains were performed in an inbred family with autosomal recessive
      Alport's syndrome (AS). A linkage study using polymorphic markers around the
      COL4A3/COL4A4 genes clearly differentiated the affected patients from healthy
      individuals. These patients were homozygous for all markers analyzed, whereas
      their parents were heterozygotes. Because of the large size of both the genes and
      the heterogeneous range of the mutations of these genes, linkage analysis by
      using highly polymorphic markers is still the method of choice in genetic
      counseling for autosomal recessive AS, as well as for the X-linked form. Although
      the distribution of alpha1 and alpha2 chains in the index patient and her
      affected sister were normal, the alpha3 and alpha4 chains were completely
      defective in the renal basement membrane (BM). The alpha5 chain could be found in
      Bowman's capsular basement membrane (BCBM) but not in the glomerular basement
      membrane (GBM). In addition, our study showed, for the first time, that the
      alpha6 chain in BCBM is spared in this form of AS. This abnormal pattern of type
      IV collagen could be a useful tool for differentiation of the autosomal recessive
      type from the X-linked type of AS.

PMID- 10074585
TI  - Renal failure resulting from infiltration by inflammatory myofibroblastic tumor
      responsive to corticosteroid therapy.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare disease of inflammatory and
      spindle cell proliferative lesions in multiple sites. Most frequently reported in
      the lungs, a variety of extrapulmonary sites have been described. We report the
      first case of IMT causing renal failure by massive bilateral renal infiltration.
      Renal function continued to deteriorate (peak serum creatinine level, 8.4 mg/dL)
      despite placement of a ureteral stent. The kidneys were diffusely enlarged on
      computed tomographic (CT) scan. Renal biopsy showed myofibroblastic proliferation
      and inflammatory infiltration. Renal failure responded favorably over weeks to
      corticosteroid therapy (serum creatinine level, 2.8 mg/dL) with a marked
      reduction in bilateral renal enlargement by CT scan.

PMID- 10074586
TI  - 1996 peritoneal dialysis--core indicators report.
AB  - The 1996 Peritoneal Dialysis-Core Indicators Study (PD-CIS) retrospectively
      reviews a random sample of peritoneal dialysis patients from the United States
      End-Stage Renal Disease (ESRD) program. Peritoneal dialysis (PD) patients are
      more likely to have a primary diagnosis of glomerulonephritis, less likely to be
      of African-American heritage, and are younger than hemodialysis patients. One
      third of PD patients now perform some form of automated peritoneal dialysis (APD)
      rather than continuous ambulatory peritoneal dialysis (CAPD). The dialysis
      prescriptions currently employed do not appear to be based on kinetic principles,
      and the intensity of dialysis achieved is below the proposed minimal guidelines
      for 30% of patients. In 1996, the mean dialysis index or wKt/Vurea for CAPD
      patients was 2.0 +/- 0.5 and was not significantly altered from the 1995 value of
      2.1. Eighty-four percent of CAPD patients perform four or fewer exchanges daily,
      and only 27% of patients have prescriptions using infusion volumes greater than 2
      L. Although hematocrits have improved since 1995, 30% of PD patients have a
      hematocrit below 30%. The mean serum albumin for PD patients is 3.5 g/dL, and 25%
      of patients have a 6-month average serum albumin value below 3.2 g/dL. In
      general, the indices monitored as predictive of health and well-being of PD
      patients afford significant opportunity for improvement.

PMID- 10074587
TI  - Successful treatment with steroid pulse therapy in a case of immunotactoid
      glomerulopathy with hypocomplementemia.
AB  - We report a case of immunotactoid glomerulopathy with severe hypocomplementemia.
      The patient was a 47-year-old woman who presented with pitting edema,
      proteinuria, and hypertension. Serological testings were negative or within
      normal limits except for hypocomplementemia. There were no findings of
      hematopoietic diseases, cryoglobulinemia, and systemic lupus erythematosus. The
      renal biopsy specimen showed membranoproliferative glomerulonephritis with
      numerous periodic acid-Schiff (PAS)-positive deposits. Under electron microscopy,
      however, microtubular structure was shown in the mesangial matrix and the
      subendothelial and subepithelial spaces of the peripheral capillary loops. These
      histological features were compatible with those of immunotactoid glomerulopathy.
      Although conventional oral steroid therapy failed to have an effect on
      proteinuria and hypocomplementemia over 3 months, steroid pulse therapy brought
      dramatic relief: complete remission of proteinuria and normalization of
      hypocomplementemia. These findings suggest that intensive immunosuppressive
      therapy may cure a kind of immunotactoid glomerulopathy with hypocomplementemia.

PMID- 10074588
TI  - Gross hematuria of uncommon origin: the nutcracker syndrome.
AB  - Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker
      syndrome," is a rare vascular abnormality responsible for gross hematuria. The
      phenomenon is attributable to the idiopathic decrease in the angle between the
      aorta and the superior mesenteric artery with consequent compression of the left
      renal vein. The entrapment of the left renal vein is not easily detectable by
      ordinary diagnostic procedures. We report two cases of gross hematuria
      (persistent in one patient and recurrent in the other) caused by "nutcracker
      phenomenon." In both cases, no remarkable findings were obtained from medical
      history, urinary red blood cells morphology, repeated urinalysis, pyelography,
      cystoscopy, or ureteroscopy. Left renal vein dilation in one case was found with
      a computed tomography (CT) scan performed on the venous tree of left kidney. The
      diagnosis of "nutcracker phenomenon" was confirmed by renal venography with
      measurement of pressure gradient between left renal vein and inferior vena cava
      in both cases. In one case, the diagnosis was complicated by the presence of
      Mycobacterium tuberculosis in urine. The "nutcracker phenomenon" is probably more
      common than thought. Early diagnosis is important to avoid unnecessary diagnostic
      procedures and complications such as the thrombosis of the left renal vein. Many
      procedures are available to correct the compression of the left renal vein
      entrapped between the aorta and the superior mesenteric artery: Gortex graft vein
      interposition, nephropexy, stenting, and kidney autotransplantation. After
      surgery, gross hematuria ceases in almost all patients.

PMID- 10074589
TI  - Management of heparin-induced thrombocytopenia during continuous renal
      replacement therapy.
AB  - Heparin-associated thrombocytopenia occurred in a patient during continuous renal
      replacement therapy (CRRT), resulting in repeated clotting of the extracorporeal
      circuit and spontaneous hemorrhage. The peripheral platelet count initially
      appeared to improve by changing to prostacyclin and dalteparin. However, repeated
      CRRT circuit clotting recurred, and the platelet count decreased once again. This
      time the synthetic heparinoid, Orgaran (danaparoid), was used and was associated
      with successful CRRT and return of the platelet count.

PMID- 10074590
TI  - Cyclosporine disposition and long-term renal function in a 500-pound kidney
      transplant recipient.
AB  - Patient size has been suggested as a risk factor in kidney transplantation. We
      have followed a recipient of a cadaver kidney who became massively obese (232 kg,
      511 lbs) 5 years posttransplantation. He has maintained stable renal function
      with no rejection episodes and at 5 years has a measured serum creatinine of 2.2
      mg/dL, creatinine clearance 42 mL/min, and urinary protein excretion of 320
      mg/24h. Both oral and intravenous cyclosporine (Sandimmune) pharmacokinetic
      studies were done on a steady-state dose of 150 mg, which represents 0.65 mg/kg
      per dose. The patient exhibited very high bioavailability, F = 95%, and an oral
      elimination T1/2 of over 21 hours. These data confirm that stable cyclosporine
      delivery in very obese recipients can be sustained by dosing normalized to the
      ideal body weight and trough level monitoring.

PMID- 10074591
TI  - Fibrillary glomerulonephritis and Charcot-Marie-Tooth disease.
AB  - We report the case of a young white man with Charcot-Marie-Tooth disease type 1
      that began at 4 years. At 15 years, he developed proteinuria, arterial
      hypertension, and renal insufficiency. Renal biopsy specimens studied by electron
      microscopy showed deposition of nonamyloidotic microfibrils. This is the first
      report of fibrillary glomerulopathy associated with this neurological disorder.

PMID- 10074592
TI  - Fibrillary glomerulonephritis in a renal allograft.
AB  - Fibrillary glomerulonephritis is an uncommon disease seen in approximately 1% of
      all native kidney biopsy specimens. We present here a case of a 40-year-old white
      woman with the rapid loss of graft function secondary to fibrillary
      glomerulonephritis within 7 days of receiving a living-related renal allograft.
      This case emphasizes the values of combining urinalysis with prompt allograft
      kidney biopsy in recipients with an elevated serum creatinine
      posttransplantation. When one encounters rapidly progressing glomerulonephritis
      or a pulmonary-renal syndrome in the immediate posttransplantation period,
      fibrillary glomerulonephritis must be considered in the differential diagnosis.
      Because of a high recurrence rate and no available treatment to modify a
      potentially malignant course of this disease, we recommend caution when
      considering these patients for transplantation.

PMID- 10074593
TI  - Carboplatin-related hematuria and acute renal failure.
AB  - Cisplatin is a potent tubular toxin with a high incidence of nephrotoxicity.
      Carboplatin is considered less nephrotoxic but can still cause tubular injury and
      interstitial nephritis in patients who have been previously treated with
      cisplatin. The affected individuals usually have nonoliguric renal failure with a
      urine output of more than a liter per day. We present a 57-year-old white woman
      with no history of renal disease who underwent a total abdominal hysterectomy and
      bilateral salpingo-oophorectomy for stage IC ovarian carcinoma. One month later,
      she received chemotherapy with paclitaxel (Taxol) and carboplatin. On the
      following day, she developed frank hematuria and flank pain associated with a
      diminished urine output. Intravenous pyelogram (IVP) showed bilateral
      hydronephrosis with a total blockage of dye flow at the level of intraureteral
      lucencies consistent with bilateral blood clots. Her coagulation profile and uric
      acid was normal. Her acute renal failure (ARF) spontaneously resolved in the
      following 24 hours, with a brisk diuresis presumably due to clot lysis. The
      follow-up IVP showed a resolution of obstructive changes. A review of the
      literature shows a previous case in which high doses of carboplatin were
      implicated as the cause of hemorrhagic cystitis, presumably by toxicity to
      transitional epithelium of the bladder. We believe that the current case
      represents carboplatin-induced damage to the transitional epithelium in the renal
      pelvi and ureters causing gross hematuria and blood clots, resulting in bilateral
      ureteral obstruction and hydronephrosis.

PMID- 10074594
TI  - MPO-ANCA necrotizing glomerulonephritis related to rheumatoid arthritis.
AB  - Two patients with rheumatoid arthritis (RA) developed necrotizing crescentic
      glomerulonephritis with high titers of anti-myeloperoxidase antibodies (MPO) in
      the absence of overt extrarenal vasculitis. We therefore suggest that in some
      patients with RA, MPO-ANCA necrotizing glomerulonephritis (GN) may occur as a
      kidney-limited form of rheumatoid vasculitis, and that RA should be added to the
      list of diseases potentially associated with necrotizing GN with anti-MPO
      antibodies. These observations also point out the importance of repeatedly
      evaluating titers of anti-MPO antibodies in the course of RA, especially if renal
      impairment or abnormal urinary sediment are present.

PMID- 10074595
TI  - Remission of the nephrotic syndrome in a patient with renal amyloidosis due to
      rheumatoid arthritis treated with prednisolone and methotrexate.
AB  - A 46-year-old woman developed nephrotic syndrome secondary to rheumatoid
      arthritis (RA). A renal biopsy showed deposition of amyloid fibrils in the
      subendothelial space of the glomerular capillary walls. After treatment with
      prednisolone (PSL, 40 mg/day), the levels of C-reactive protein (CRP) and serum
      amyloid A decreased to within normal limits for 2 weeks. However, the nephrotic
      syndrome persisted for 6 months after the therapy. To maintain the suppression of
      disease activity and to reduce PSL, methotrexate (5 mg/week) was added. The
      nephrotic syndrome resolved gradually, and the level of serum albumin returned to
      normal. Although renal prognosis of patients with nephrotic syndrome due to
      amyloidosis caused by RA has been considered poor, adequate and long-term
      treatment of RA with antiinflammatory drugs, including PSL and methotrexate, is
      useful for patients with secondary amyloidosis complicated by RA.

PMID- 10074597
TI  - Lambda light chain induced nephropathy: a rare cause of the Fanconi syndrome and
      severe osteomalacia.
AB  - The Fanconi syndrome is a generalized disorder of proximal renal tubular
      transport characterized by wasting of phosphate, amino acids, glucose,
      bicarbonate, and uric acid. The association of the acquired Fanconi syndrome with
      lambda light-chain proteinuria is rare. We report the third case in the English
      language literature. A 65-year-old man presented with severe pelvic pain.
      Investigations showed an elevated serum creatinine level, and a 24-hour urine
      collection contained 2.56 g protein. The Fanconi syndrome was diagnosed, with
      findings of phosphaturia, glycosuria, and aminoaciduria. Bence Jones protein
      (lambda sub-type) was present in the urine at a concentration of 0.58 g/L.
      Monocytic cells in the bone marrow and proximal tubular cells in the kidney
      contained cytoplasmic crystalline inclusions. Undecalcified bone sections
      confirmed the clinical diagnosis of osteomalacia. The patient was treated with
      phosphate, calcium, and ergocalciferol and experienced significant symptomatic
      improvement. The Fanconi syndrome caused by light-chain deposition in proximal
      tubular cells is well described in the literature. However, it is rare for the
      light chains to be of the lambda subtype. This may reflect differences in the
      physicochemical properties of kappa and lambda light chains.

PMID- 10074598
TI  - Bilateral fibromuscular dysplasia in identical twins.
AB  - Fibromuscular dysplasia is an arterial occlusive disorder that often affects the
      renal arteries and leads to renovascular hypertension. The cause of this disease
      is unknown. However, the occurrence in siblings suggests that genetic factors may
      play a role. We describe two cases involving hypertensive identical twins with
      fibromuscular dysplasia of the renal arteries. This unique clinical case
      reinforces a possible hereditary nature of this arterial occlusive disorder.

PMID- 10074602
TI  - Left leg paralysis in a renal transplant.
AB  - The postoperative course of renal transplant patients is often complicated by
      opportunistic infection. Up to 4% of posttransplant infections are caused by
      Nocardia species. We present an unusual case of a nocardial spinal cord abscess
      that caused left leg paralysis.

PMID- 10074601
TI  - Renal artery rupture secondary to pretransplantation Candida contamination of the
      graft in two different recipients.
AB  - Infected graft transplantation is an unwelcome complication that may lead to
      serious consequences in the immunosuppressed host. It can be caused by infection
      of the donor or by contamination of the organ during harvest, preservation and
      handling, or at transplantation. With current donor evaluation protocols, the
      risk of transmitting infections by exogenous contaminated grafts seems to be more
      frequent than true donor-transmitted infections. Nevertheless, although rare and
      usually free of clinically significant sequelae, if contamination is by some
      virulent organisms such as Staphylococcus aureus, gram-negative bacilli, or
      fungi, severe complications may occur. We report the clinical outcome of liver,
      heart, and kidney recipients from a single donor. Both renal allografts had to be
      removed because of renal artery rupture secondary to Candida albicans infection.
      Careful donor evaluation before transplantation, unusually early presentation of
      mycosis leading to anastomotic renal artery disruption, the histopathologic
      findings of the grafts, and the absence of Candida infection in the liver and
      heart recipients make us believe that exogenous contamination of the grafts
      occurred during donor procedure, kidney processing, or at transplantation. In
      summary, because infected grafts can lead to serious complications, besides
      careful donor screening, it is important to achieve early recognition of
      contaminated organs by culturing the perfusate to start specific antibiotic or
      antifungal therapy after transplantation if necessary and avoid the rare but, in
      this case, fatal consequences of these infections.

PMID- 10074603
TI  - IgA antiglomerular basement membrane disease associated with bronchial carcinoma
      and monoclonal gammopathy.
AB  - Antiglomerular basement membrane (anti-GBM) disease is characterized by a linear
      deposition of immunoglobulins along the glomerular basement membrane. A 67-year
      old man with a recently discovered monoclonal gammopathy of unknown significance
      (MGUS) presented with microscopic hematuria, nephrotic-range proteinuria, and
      rapidly deteriorating renal function after a pneumonia. Renal histology showed a
      crescentic glomerulonephritis; immunohistology showed intense linear staining of
      the GBM with immunoglobulin A (IgA) and moderate linear staining with kappa and
      lambda light chains. Screening for systemic disease, including diabetes mellitus,
      lupus erythematodes disseminatus, cryoglobulinemia, was negative. Serological
      tests for detection of anti-GBM antibodies were positive for IgA class and
      negative for IgG. Further examination indicated a bronchial carcinoma T2N2M0.
      This clinical report adds new information to the spectrum of anti-GBM disease and
      suggests that neoplasia may be associated with unusual exposure of and/or immune
      response to epitopes in the GBM.

PMID- 10074604
TI  - Recovery from prolonged metabolic acidosis due to accidental ethylene glycol
      poisoning.
AB  - In this report, we describe a case of accidental ethylene glycol poisoning in a
      90-year-old woman. Despite a delay in diagnosis and treatment of over 24 hours,
      this patient recovered completely from profound and lengthy metabolic acidosis.
      She is therefore the oldest known survivor of severe ethylene glycol
      intoxication. We review 79 additional cases of ethylene glycol intoxication
      reported in the literature since 1976 and comment on diagnostic, therapeutic and
      prognostic features of this form of poisoning.

PMID- 10074605
TI  - Acute renal failure from multiple myeloma precipitated by ACE inhibitors.
AB  - Renal failure in multiple myeloma can be precipitated during hemodynamic
      perturbances of renal blood flow, as seen secondary to volume depletion,
      radiocontrast dye, and nonsteroidal anti-inflammatory agents. We report two cases
      of acute renal failure that developed suddenly after initiation of angiotensin
      converting enzyme (ACE) inhibitor, both with biopsy-proven cast nephropathy. ACE
      inhibitors may contribute to the intratubular light chain cast formation and
      acute "myeloma kidney" in susceptible patients.

PMID- 10074606
TI  - Peritoneal dialysis-associated peritonitis caused by Propionibacteria species.
AB  - There are an increasing number of reports about unusual causes of peritonitis in
      peritoneal dialysis (PD) patients. The Propionibacteria species is a
      microorganism that is a normal skin flora. Under the presence of certain risk
      factors, it may produce serious infections. Patients at risk of having
      Propionibacteria sp infections have malignancy, diabetes mellitus, foreign
      bodies, or immunodeficiency. We describe a PD-associated peritonitis in a 51-year
      old woman that was caused by Propionibacteria sp. This patient's risk factors for
      developing Propionibacteria sp peritonitis include a history of CREST syndrome,
      malignancy of the breast, and recent catheter surgery. To our knowledge, this is
      the first case of a PD-associated peritonitis caused by Propionibacteria sp
      reported in the literature.

PMID- 10074607
TI  - A case of cimetidine-induced acute tubulointerstitial nephritis associated with
      antineutrophil cytoplasmic antibody.
AB  - We present a case of acute tubulointerstitial nephritis (ATIN) that developed in
      a 63-year-old man who had been taking cimetidine for treatment of a gastric
      ulcer. The constellation of clinical, laboratory, and histopathologic findings
      suggested drug-induced ATIN. Of interest, the patient had antineutrophil
      cytoplasmic antibody (ANCA) in his sera, reactive with myeloperoxidase, elastase,
      and lactoferrin. Prominent renal histological features included marked plasmacyte
      infiltration into the renal interstitium. Withdrawal of cimetidine resulted in
      complete resolution of renal findings, and the titers of ANCA concomitantly
      declined. Thus, cimetidine may have played a causative role in the development of
      ANCA-associated ATIN.

PMID- 10074608
TI  - Chronic lymphocytic leukemia-associated membranous glomerulopathy: remission with
      fludarabine.
AB  - In some individuals, chronic lymphocytic leukemia (CLL) may be associated with
      glomerular disease from membranous nephropathy with resultant nephrotic syndrome.
      CLL is characterized by abnormal immunoregulation with a malignant clonal
      proliferation of lymphocytes. The association between the abnormal clone and
      nephrotic syndrome is suggested in some cases by the remission of proteinuria
      with a reduction in abnormal lymphocyte number after treatment with
      antineoplastic agents. For the first time, we describe a patient with CLL and
      associated membranous glomerulopathy whose nephrotic syndrome remitted after
      treatment with fludarabine, a new purine analogue used in the treatment of
      refractory CLL.

PMID- 10074609
TI  - Pauci-immune rapidly progressive glomerulonephritis after nephrectomy in a renal
      donor.
AB  - Idiopathic rapidly progressive glomerulonephritis (RPGN) is a clinicopathologic
      syndrome in which glomerular damage is accompanied by a rapid and progressive
      decline in renal function, usually resulting in irreversible renal failure in
      weeks or months. We report the occurrence of pauci-immune RPGN, more specifically
      microscopic polyarteritis nodosa (PAN), in a 60-year-old woman 15 months after
      donor nephrectomy, and 3 months after documentation of intact, residual renal
      function. The transplanted kidney continues to function well in the recipient, 6
      years posttransplantation, and 4.5 years beyond destruction of the donor's
      contralateral kidney by RPGN. The donor underwent cadaveric renal transplantation
      after 2 years on dialysis, and at the 3-year mark has intact renal function.
      These intriguing observations strongly argue that host environmental factors,
      rather than intrarenal factors, play a major causative role in the pathogenesis
      of RPGN.

PMID- 10074610
TI  - Bilateral emphysematous pyelonephritis caused by Candida infection.
AB  - Emphysematous pyelonephritis is a rare, often severe infection of one or both
      kidneys that is most often caused by bacterial infection. Surgical intervention
      is often necessary. We describe a case of a diabetic patient with bilateral
      emphysematous pyelonephritis caused by Candida infection that was treated
      conservatively. Renal function recovered almost completely in spite of giving a
      potential nephrotoxic drug for 6 weeks.

PMID- 10074611
TI  - Acute renal failure in a patient with AIDS: histoplasmosis-induced granulomatous
      interstitial nephritis.
AB  - Although the most frequent cause of acute renal failure (ARF) in patients with
      AIDS is acute tubular necrosis (ATN) secondary to ischemic renal injury from
      septicemia, a spectrum of causes may result in ARF in these patients. We report a
      patient with AIDS who developed ARF and was found to have granulomatous
      interstitial nephritis as a result of disseminated histoplasmosis. Histoplasma
      capsulatum was seen in the interstitium of the kidney on renal biopsy. The
      patient was treated with amphotericin B and itraconazole. Although he continues
      to require hemodialysis 3 months after his initial presentation, his other
      presenting symptoms have resolved with antifungal therapy. We also discuss the
      literature on disseminated histoplasmosis and renal failure.

PMID- 10074612
TI  - Hypotension, bradycardia, and asystole after high-dose intravenous
      methylprednisolone in a monitored patient.
AB  - We report a case of hypotension, bradycardia, and asystole after intravenous
      administration of high-dose methylprednisolone in a 73-year-old patient who
      underwent electrocardiographic (ECG) monitoring throughout the episode. There was
      a history of ischemic cardiac disease 9 years earlier. The patient was admitted
      with a pulmonary-renal syndrome with hemoptysis, rapidly progressive renal
      failure, and hypoxemia that required mechanical ventilation in the intensive care
      unit. After receiving advanced cardiopulmonary resuscitation, the patient
      recovered cardiac rhythm. The ECG showed a junctional rhythm without ventricular
      arrhythmia. This study reviews the current proposed mechanisms of sudden death
      after a high dose of intravenous methylprednisolone (IVMP). These mechanisms are
      not well understood because, in most cases, the patients were not monitored at
      the moment of the event. Rapid infusion and underlying cardiac disease were
      important risk factors in the case reported here, and the authors discount
      ventricular arrhythmia as the main mechanism.

PMID- 10074613
TI  - [The prognostic value of eicosanoids in the acute respiratory distress syndrome].
AB  - BACKGROUND: There is a great number of agents involved in the acute respiratory
      distress syndrome (ARDS) physiopathology, and some of them may have a prognostic
      value. The objective of the present study has been to analyse the prognostic
      value of eicosanoids in this syndrome. MATERIAL AND METHOD: A prospective study
      with 21 consecutive ARDS patients admitted to the intensive care unit of a
      therapy hospital in Barcelona, Spain, was carried out. In the first 48 h of the
      ARDS diagnosis, at baseline, the plasma levels, (in peripheral arterial and
      pulmonary arterial samples) of thromboxane B2 (TXB2), prostaglandin F1-alpha)
      (PGF1-alpha) and leukotriene B4 (LTB4) were analysed by RIA. Simultaneously we
      measured different pulmonary and systemic hemodynamical variables, as well as the
      pulmonary gas exchange data. We also studied the venous levels of the same
      eicosanoids in 17 healthy adults, used as reference. RESULTS: Plasma levels of
      eicosanoids in the ARDS patients were higher than reference subjects (p < 0.05).
      No differences were observed between systemic arterial and pulmonary arterial
      values. From all the eicosanoids, only LTB4, (in both systemic arterial and
      pulmonary blood), was correlated with LIS (r = 0.49, p < 0.05; and r = 0.45, p <
      0.05, respectively). Patients who did not survive presented a lower systemic
      pulmonary arterial gradient of eicosanoids levels than survivors (-1.27 vs -0.10
      ng/ml; p < 0.01). CONCLUSIONS: In our ARDS patients only LTB4 plasma levels
      correlated with the severity of respiratory failure. Patients who did not survive
      presented a lower LTB4 gradient than survivors.

PMID- 10074614
TI  - [The risk factors and bone mineral density in women on long-term levothyroxine
      treatment].
AB  - BACKGROUND: It is controversial if the long-term treatment with thyroid hormone
      given at substitutive or suppressive doses has a negative effect on bone
      metabolism. In previous reports the lack of ultrasensitive TSH assays and
      densitometers with adequate precision, and the heterogeneity of the patients
      analyzed could explain these discordant results. PATIENTS AND METHODS: We have
      assessed bone mineral density (BMD) in 43 premenopausal and 53 postmenopausal
      women, who underwent near total thyroidectomy and I-131 ablation due to
      differentiated thyroid cancer, that have been followed up (mean duration, 75.5
      [43] months) with suppressive thyroid hormone treatment (mean dose, 170 [42]
      micrograms) in our hospital. Patients with history of hyperthyroidism were
      excluded. Lumbar BMD (L2-L4) and BMD in three different sites of hip were
      measured (dual X-ray densitometry) to determine the contribution of several
      clinical and risk factors associated with thyroid hormone therapy given to BMD.
      RESULTS: We have not found significant decrease in BMD at spine or hip when
      patients were compared with healthy, age and sex matched. Age (inverse
      correlation) and weight (direct correlation) were the variables mostly
      influencing BMD). Histologic type of thyroid neoplasia, doses of thyroid
      hormones, thyroid hormone levels and duration of follow-up, were not associated
      with changes in BMD. A decrease in calcium intake in postmenopausal and less
      physical activity in premenopausal women were related with a decreased lumbar
      BMD. CONCLUSIONS: During long-term treatment of female patients with thyroid
      hormones, other risk factors should be studied in order to prevent possible loss
      of bone mass.

PMID- 10074616
TI  - [Informed or uninformed consent? The danger of defensive medicine].

PMID- 10074615
TI  - [An analysis of patient information sheets for obtaining informed consent in
      clinical trials].
AB  - BACKGROUND: The written information provided to the potential participants in a
      clinical trial must have certain qualitative and quantitative characteristics to
      reach the ethical requirements governing the theory of the informed consent.
      MATERIAL AND METHODS: In a sample of 101 clinical trial protocols approved in two
      Spanish university general hospitals, the following items were evaluated: a) the
      amount and quality of the written information given to the patient, in accordance
      with the established in the Spanish legislation; b) the formal readability of
      this written forms, by means of the Flesch method, and c) the level of complexity
      of the vocabulary, by means of the number of non-comprehensible words for two
      volunteers unaware of the health professions, with high studies. RESULTS: The
      balance of benefits and risks, the identification and the way of contact with the
      main investigator, the description of the alternative treatments and the
      specification of the compensations in case of lesions were the items with highest
      noncompliance. The mean global readability by means of the index of Flesch was of
      -12.7 (text with a high level of complexity). The mean percentage of words non
      comprehensible for the volunteers that analyzed the texts was 0.3%. CONCLUSIONS:
      The written form of information provided to the patient in the clinical trials
      developed in Spain has serious deficiencies, either in their formal readability
      (complexity of the linguistic structure) or in the amount and quality of the
      information that provides. These deficiencies could have a wrong influence in the
      appropriate obtention of the informed consent from the patients.

PMID- 10074617
TI  - [Mitochondrial diabetes: a distinct diabetes?].

PMID- 10074618
TI  - [Diabetes mellitus associated with the A3243G mutation of mitochondrial DNA.
      Apropos a case].
AB  - The mitochondrial A3243G mutation of the tRNA(Leu) has been described in
      pedigrees with maternally inherited diabetes mellitus and deafness. Ten diabetic
      patients with sensorineural deafness were studied. Polymerase chain reaction and
      enzyme restriction analysis with Apa I were performed. The mutation was found in
      heteroplasmy in only one patient (1/10). She was a 43-years-old woman with
      maternally inherited diabetes and deafness since she was 29. The association of
      sensorineural deafness and maternal inherited diabetes are the clues to suspect
      this subtype of diabetes.

PMID- 10074619
TI  - [Difficulties in the physician-patient relationship in somaticizers (I). Patient
      expectations].

PMID- 10074620
TI  - [Fever, general malaise, adenopathies and hepatosplenomegaly in a 17-year-old
      woman after an allogeneic transplant of peripheral blood hematopoietic
      progenitors for chronic myeloid leukemia].

PMID- 10074621
TI  - [The diagnostic yield of cardiac troponin I versus the classic markers of a
      myocardial lesion in a clinical model of acute myocardial necrosis].

PMID- 10074622
TI  - [Lumbar epidural infiltration in a case of chronic lymphatic leukemia].

PMID- 10074623
TI  - [Goya's disease: the Vogt-Koyanagi-Harada syndrome or lead poisoning?].

PMID- 10074624
TI  - [The restoration of old buildings: a new source of lead poisoning].

PMID- 10074625
TI  - [Mixed cryoglobulinemia due to hepatitis C viral infection in a post-liver
      transplant patient].

PMID- 10074626
TI  - [The conservative treatment of a pancreaticopleural fistula without a
      pseudocyst].

PMID- 10074627
TI  - [The genotype of the hepatitis C virus in patients with essential mixed
      cryoglobulinemia].

PMID- 10074628
TI  - [Evidence-based medicine: is there not a better translation?].

PMID- 10074629
TI  - [The polymerase chain reaction as a marker of cytomegalovirus infection in heart
      transplant recipients].
AB  - BACKGROUND: To evaluate the usefulness of PCR in peripheral blood leukocytes for
      the diagnosis of CMV infection and for prognosis of CMV disease in patients with
      heart transplantation. PATIENTS AND METHODS: A total of 54 heart transplant
      recipients included in a protocolized virological follow-up with blood samples
      (total samples: 594). Mean time of follow-up: 14.8 months (range 1-34 months). We
      compared a qualitative nested PCR with tube culture (CC), shell vial culture (SV)
      and pp65 quantitative antigenemia test (AGC). RESULTS: PCR was the most sensitive
      test (89.9%) followed by AGC (68.1%), SV (42.6%) and CC (33.4%). Specificity: 80
      samples were positive only by PCR, 77 of which form patients with virologically
      documented CMV active infection, so they were considered as true positives. Three
      samples were from 2 patients in which the unique positive marker was PCR. If we
      considered these results as false positive, the calculated specificity was 99.0%.
      PCR was the first positive marker in 44 out of 45 patients with active CMV
      infection. In 9 of these patients no other viral marker was positive in the first
      positive sample, except for PCR. A total of 16 episodes of CMV disease were
      observed along the study, and a positive PCR result was detected in 15 of them.
      The remaining patient did not show amplification with the set of primers used in
      this study, but it gave a positive PCR by amplifying with a different primer
      pair. Positive predictive value of PCR for CMV disease was low (33.3%). Thus, a
      positive PCR result did not allow to distinguish between asymptomatic infection
      and CMV disease. CONCLUSIONS: In heart transplantation recipients CMV-PCR is a
      highly sensitive, specific and early marker of CMV infection but its positive
      predictive value for CMV disease seems unsatisfactory.

PMID- 10074630
TI  - [Consumption patterns and the principal sources of lipids and fatty acids in the
      Spanish cohort of the European Prospective Investigation on Diet and Cancer
      (EPIC). The EPIC Group in Spain].
AB  - BACKGROUND: To evaluate the fat consumption and main sources of specific fatty
      acids in adults from the south and north of Spain. SUBJECTS AND METHODS: Dietary
      data from 25,816 women and 15,635 men, aged 29-69 years, participants in the
      European Prospective Study on Cancer and Nutrition (EPIC) recruited in the north
      (Asturias, Navarra and Guipuzcoa) and south (Murcia and Granada) of Spain, were
      used in a cross-sectional study. Information of habitual diet was collected by
      personal interview by means a computerized version of a diet history
      questionnaire. Energy and nutrient intake was estimated using a conversion table
      of more than 700 items compiled for the study in Spain. RESULTS: Saturated fatty
      acid (SFA), monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid
      (PUFA) provided respectively between 11.2 to 13.3%, 15.6 to 20.0% and 5.6 to 7.4%
      of total calories intake. MUFA/SFA ratio showed values from 1.7 in males to 1.3
      in females, the PUFA/SFA ratio showed values from 0.7 in males to 0.5 in males
      and females, and the n-6/n-3 ratio showed values from 10.8 in females to 7.4 in
      males. Olive oil was the major contributor (78% in women and 67% in men) of
      vegetable oils intake, which provides between 7 to 8% of total calories intake
      and between 31 to 48% of MUFA intake. Daily intake of n-3 fatty acids from fish
      was between 0.3 to 1.2 g. In most of the provinces whole milk and cheeses in
      women and preserved meat in men were the major contributors of SFA intake while
      contribution of red meat was less important. CONCLUSION: Patterns of fat
      consumption in adult population from the north and south of Spain are very
      similar.

PMID- 10074631
TI  - [Diets enriched with monounsaturated fatty acids and omega-3 polyunsaturated
      fatty acids decrease blood pressure without changing the plasma insulin
      concentration in healthy subjects].
AB  - BACKGROUND: Plasma glucose, insulin and blood pressure are wellknown
      cardiovascular risk factors, which may be influence by dietary factors. The aim
      of the study was to investigate whether changes in dietary fatty acids could
      modify plasma concentration of glucose, insulin and mean blood pressure (MBP).
      SUBJECTS AND METHODS: Forty two subjects (18 women and 24 men) were placed in
      four consecutive five week diet periods. Energy intake from proteins,
      carbohydrates and fats was constant during the study and there was only changes
      on fatty acids composition. First period was enriched on saturated fatty acids
      (SFA), second period on monounsaturated fatty acids (MUFA) and third and fourth
      periods were enriched on polyunsaturated fatty acids (PUFA). Fourth period was
      also enriched on PUFA n-3. RESULTS: No significant changes were found on glucose
      and insulin plasma concentration. However, a significant effect was detected on
      MBP on total population (p < 0.0001) and by gender. MUFA and PUFA n-3 enriched
      diet decreased significantly MBP compared to SFA enriched diet AGS (85.7, SD 9.1,
      87.3, SD 8.7 y 90.3, SD 8.8 mmHg, respectively). In addition, a weak (r = 0.28)
      but significant (p = 0.002) correlation was found between MBP and plasma insulin.
      CONCLUSIONS: Diets enriched on MUFA fatty acids and n-3 fatty acids decrease
      significantly MBP without modifying glucose and insulin plasma concentration.

PMID- 10074632
TI  - [North and south].

PMID- 10074633
TI  - [The hunter hunted].

PMID- 10074634
TI  - [Epidemic rhabdomyolysis due to the eating of quail. A clinical, epidemiological
      and experimental study].
AB  - BACKGROUND: Few toxic outbreaks by quails ingestion have been described, none in
      Spain, and the toxic hasn't been identified. A toxic outbreak, by quails
      ingestion that ate Galeopsis ladanum seeds, is described and an animal model is
      developed. PATIENTS AND METHODS: A rhabdomyolysis outbreak by quails ingestion is
      studied clinical and epidemiologically. Quails crops were analyzed and 20
      patients were studied. A murine model was developed. Alcaloid content in
      Galeopsis ladanum seeds and quail meat was measured. RESULTS: Twenty patients
      suffered from rhabdomyolysis (myalgia, increase of muscular enzymes and
      myoglobinuria) by ingestion of quails that ate Galeopsis ladanum seeds as it
      could be seen at their crops. Six patients needed hospital care but evolution was
      benign. Rats fed with quails that ate Galeopsis ladanum seeds had higher
      creatinkinase (CK) levels than controls rats (near significance, p = 0.0588).
      Several alcaloids, stachydrine included, was detected in seeds. Another alcaloid
      no identified was detected in quails meat. CONCLUSIONS: Quails that eat Galeopsis
      ladanum seeds are toxic for human beings, causing rhabdomyolysis. A plant
      alcaloid could be the toxic involved in the outbreak.

PMID- 10074635
TI  - [Difficulties in the physician-patient relationship in somaticizers (II). The
      reactions of the professional and the types of relationship].

PMID- 10074636
TI  - [A consensus document on the study of the contacts of tuberculosis patients. The
      Contacts Study Group of the Research Unit on Tuberculosis in Barcelona (UITB)].

PMID- 10074637
TI  - [The clinical impact of symptomatic visceral leishmaniasis on HIV-1 infection].

PMID- 10074638
TI  - [The usefulness of a nursing extra-hospital monographic consultation in the
      treatment of smoking habit].

PMID- 10074639
TI  - [The Schnitzler syndrome. A case report].

PMID- 10074640
TI  - [The night hospital: another alternative to traditional hospitalization].

PMID- 10074641
TI  - Haemolysis during cardiopulmonary bypass: an in vivo comparison of standard
      roller pumps, nonocclusive roller pumps and centrifugal pumps.
AB  - Cardiopulmonary bypass (CPB) involves the use of either an occlusive roller pump
      or centrifugal pump. Damage to blood elements, including haemolysis, may arise
      from occlusion when using a roller pump; the appropriate degree of occlusion has
      not yet been determined scientifically. Centrifugal and nonocclusive roller pumps
      are reputed to reduce haemolysis. The objective of this study was to compare
      haemolysis caused by a standard roller pump with a dynamically set nonocclusive
      roller pump and with a centrifugal pump. We prospectively randomized 60 patients
      undergoing routine coronary artery surgery into three groups: standard roller
      pump (STD, n = 20), dynamically set roller pump (DYN, n = 20), or centrifugal
      pump (CEN, n = 20). The level of plasma free haemoglobin (FHb) was measured
      preoperatively, and the rate of formation of FHb (in mg/dl/min) was determined at
      the end of the ischaemic phase and at the end of CPB. Cardiotomy suction blood
      was isolated for the ischaemic phase and returned before the end of CPB. It was
      found that there were no differences between the groups in demographic or
      operative variables. The rate of formation of FHb at the end of the ischaemic
      phase was similar for all groups (STD 0.108 +/- 0.10, DYN 0.117 +/- 0.08, CEN
      0.129 +/- 0.07). At the end of CPB, after return of the cardiotomy suction blood,
      there was a significant (< 0.001) increase in the rate of formation of FHb in all
      groups. The increase was similar for each of the groups (STD 0.424 +/- 0.17, DYN
      0.481 +/- 0.20, CEN 0.471 +/- 0.18). We conclude that the rates of haemolysis are
      similar for each of the pump types, and no benefit is conferred by the use of
      either a dynamically set roller pump or a centrifugal pump compared with the
      standard roller pump. The return of the cardiotomy suction blood to the
      circulation is the principal source of plasma free haemoglobin.

PMID- 10074642
TI  - In vitro evaluation of new surface coatings for extracorporeal circulation.
AB  - Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This
      exposure may activate the cellular and humoral inflammatory systems, resulting in
      inflammatory reactions and organ dysfunction. Coating the inner surfaces of the
      bypass circuit may help alleviate these side-effects. The objective of this study
      was to determine the influence of two new surface treatments on blood cell and
      complement activation. Oxygenator and tubing sets coated with synthetic polymers
      (n = 7) or heparin (n = 7) were compared to uncoated sets (n = 7) in an in vitro
      model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The
      inflammatory response was assessed at regular intervals by platelet counts, and
      activation of complement, leucocytes and platelets. We found that the median
      platelet counts decreased from 127 to 122 x 10(9)/l (not significant, NS) in the
      synthetic polymer sets, from 96 to 88 x 10(9)/l (NS) in the heparin-coated sets,
      and from 93 to 54 x 10(9)/l (p < 0.01) in the uncoated sets after 2 h of
      recirculation. There were significant differences in platelet counts between the
      coated sets and the uncoated set at end of experiments (p < 0.05). Beta
      thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from
      166 to 352 ng/ml (p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml (p
      < 0.01), and in the uncoated sets from 301 to 3149 ng/ml (p < 0.01) after 2 h of
      recirculation. The differences in BTG at termination of the experiments were
      significant among all three sets (p < 0.05). Myeloperoxidase (MPO) concentrations
      in the synthetic polymer sets increased from 63 to 86 micrograms/l (p < 0.01), in
      the heparin-coated sets from 90 to 208 micrograms/l (p < 0.01), and in the
      uncoated sets from 122 to 513 micrograms/l (p < 0.01) after 2 h of recirculation.
      The differences in MPO at termination of the experiments were significant among
      all three groups (p < 0.01). There were no significant differences at termination
      of the experiments among the three sets regarding complement activation as
      measured by C3 activation products and the terminal complement complex. We
      conclude that in the current in vitro model of a CPB circuit, the synthetic
      polymer coating and the heparin coating caused significantly less platelet loss
      and granulocyte and platelet activation than the uncoated surface (p < 0.05). The
      synthetic polymer coating caused significantly less granulocyte and platelet
      activation than the heparin coating (p < 0.05). There was moderate complement
      activation within each group, but no significant differences among the three
      groups.

PMID- 10074643
TI  - Haemocompatibility of paediatric membrane oxygenators with heparin-coated
      surfaces.
AB  - Extracorporeal circulation (ECC) in paediatric patients with heparin-coated
      oxygenation systems is rarely investigated. The objective of this study was to
      evaluate, preclinically, the haemocompatibility of paediatric membrane
      oxygenators with heparin-coated surfaces. We compared 16 paediatric membrane
      oxygenators (Minimax, Medtronic) in an in vitro heart-lung machine model with
      fresh human blood. Eight of these oxygenation systems had a covalent heparin
      coating (Carmeda bioactive surface). After 90 min simulated ECC, the heparin
      coated systems showed significantly higher platelet count, lower platelet-factor
      4 release, reduced contact activation (factor XIIa and kallikrein), and lower
      neutrophil elastase levels (p < 0.05), compared to the noncoated oxygenator
      group. More biocompatible materials for paediatric operations may ameliorate the
      various postperfusion syndromes arising from ECC procedures, particularly
      unspecific inflammation, hyperfibrinolysis and blood loss.

PMID- 10074644
TI  - Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine
      and dopexamine.
AB  - Liver blood flow is reduced after cardiopulmonary bypass (CPB) and both dopamine
      and dopexamine are used to overcome this. This study compares the effects of
      these agents on liver blood flow. Thirty patients undergoing elective coronary
      artery bypass graft surgery were randomized into three groups (n = 10 per group).
      Six hours after surgery baseline liver blood flow was determined by the
      percentage disappearance rate of indocyanine green measured by dichromatic
      auricular densitometery. Patients then received infusions of either: (1) placebo
      (dextrose 5%); (2) dopamine (4 micrograms/kg/min); (3) dopexamine (1
      microgram/kg/min increasing to 2 micrograms/kg/min). One hour after infusion,
      liver blood flow measurements were repeated. In the dopexamine group the infusion
      was increased and the measurements repeated another hour later. We found that
      patient-specific variables and operative details were similar for all groups.
      Postoperative cardiac index and heart rate were increased significantly by
      dopamine (cardiac index 2.82 +/- 0.46 l/m/m2 vs 3.28 +/- 0.67 l/m/m2: p < 0.001
      and heart rate 87.5 +/- 13.2 vs 96 +/- 16: p < 0.05) and dopexamine at 2
      micrograms/kg/min (cardiac index 2.71 +/- 0.53 l/m/m2 vs 3.45 +/- 0.67 l/m/m2: p
      < 0.05 and heart rate 89.0 +/- 18.9 vs 107.4 +/- 13.6: p < 0.001) compared to
      placebo (cardiac index 2.97 +/- 0.8 l/m/m2 vs 3.18 +/- 0.9 l/m/m2: p > 0.05 and
      heart rate 77.2 +/- 7.4 vs 77.3 +/- 8: p > 0.05) despite similar atrial and
      systemic arterial pressures. The disappearance rate of indocyanine green was not
      altered during infusion of placebo group (9.0 +/- 3.2%/min vs 7.9 +/- 3.0%/min: p
      > 0.05) or dopexamine at 1 microgram/kg/min (9.7 +/- 3.1%/min vs 11.2 +/-
      4.1%/min: p > 0.05). The disappearance rate was increased with dopamine (6.7 +/-
      3.7%/min vs 11.8 +/- 3.0%/min: p < 0.05) and dopexamine 2 micrograms/kg/min (9.7
      +/- 3.1%/min vs 13.5 +/- 3.2%/min: p < 0.05). This indicates a 76% increase in
      liver blood flow with dopamine and a 38% increase with dopexamine. We conclude
      that dopamine 4 micrograms/kg/min and dopexamine 2 micrograms/kg/min increase
      liver blood flow, although this may, in part, be related to an increase in
      cardiac output. Dopexamine shows no advantage over dopamine in enhancing liver
      blood flow after CPB.

PMID- 10074645
TI  - Inhaled nitric oxide improves hemodynamics in patients with acute pulmonary
      hypertension after high-risk cardiac surgery.
AB  - Severe pulmonary hypertension and right-sided circulatory failure (RSCF)
      represent an increasing cause of morbidity and mortality in patients undergoing
      high-risk cardiac surgery. Increased pulmonary vascular resistance in the setting
      of cardiopulmonary bypass (CPB) may further lead to decrease blood flow across
      the pulmonary vascular bed; thereby decreasing left ventricular filling and
      cardiac output. Current management techniques for RSCF include both nonspecific
      vasodilator and inotropic agents (often limited by systemic hypotension) and the
      placement of right ventricular assist devices (associated with increased
      perioperative morbidity). Inhaled nitric oxide (NOi) represents a novel, specific
      pulmonary vasodilator that has been proven efficacious in these clinical
      settings. We evaluated 34 patients in 38 operations who underwent cardiac surgery
      at Columbia Presbyterian Medical Center, and who received NOi (20 ppm) through a
      modified ventilatory circuit for hemodynamically significant elevations in
      pulmonary vascular resistance. Nine patients underwent cardiac transplantation,
      three patients bilateral lung transplantation, 16 patients left ventricular
      assist device placement and 10 patients routine cardiac surgery. Patients
      receiving NOi exhibited substantial reductions in mean pulmonary artery pressure
      (mPAP) (34.6 +/- 2.0 to 26.0 +/- 1.7 mmHg, p < 0.0001), with improvements in
      systemic hemodynamics, mean arterial pressure (68 +/- 3.1 to 75.9 +/- 2.0 mmHg, p
      = 0.006). In five cases, patients could not be weaned from CPB until NOi was
      administered. Patients were maintained on NOi from 6 to 240 h postoperatively
      (median duration 36 h). Inhaled NO induces substantial reductions in mPAP and
      increases in both cardiac index and systemic blood pressure in patients
      displaying elevated pulmonary hemodynamics after high-risk cardiac surgery. NO
      is, therefore, a useful adjunct in these patients in whom acute pulmonary
      hypertension threatens right ventricular function and hemodynamic stability.

PMID- 10074646
TI  - A new technique for measuring cardiac output and shunt fraction during venovenous
      extracorporeal membrane oxygenation.
AB  - A new indicator dilution technique is described for measuring cardiac output and
      shunt fraction in patients undergoing venovenous extracorporeal membrane
      oxygenation (ECMO). Shunt fraction is the proportion of the ECMO pump flow which
      recirculates through the ECMO circuit (passing directly from the inflow cannula
      to the outflow cannula) instead of flowing through the pulmonary and systemic
      circulations. The indicator is an isotonic (150 mmol/l) solution of lithium
      chloride which is injected into the ECMO flow returning to the patient. Two
      lithium sensors are used simultaneously to record the resulting lithium dilution
      curves in arterial blood and in the blood in the ECMO circuit. Cardiac output and
      shunt fraction are derived from these curves. The techniques, which is simple and
      safe, provides measurements that allow optimal adjustment of ECMO flow and
      cardiovascular support.

PMID- 10074647
TI  - Lipid peroxidation during initiation of extracorporeal membrane oxygenation after
      hypoxia in endotoxemic rabbits.
AB  - Initiation of extracorporeal membrane oxygenation (ECMO) in septic children with
      severe respiratory failure often improves oxygenation but not pulmonary function.
      The factors affecting pulmonary function following onset of ECMO are not
      completely understood, but are thought to involve injury mediated, in part, by
      reactive oxygen species. We hypothesized that induction of ECMO using 100% oxygen
      as the sweep gas through the oxygenator would increase lipid peroxidation in
      endotoxin-primed animals after severe hypoxia. We further speculated that
      provision of oxygenated blood to the pulmonary circulation via venovenous ECMO
      would promote a greater degree of oxidative damage to the lung as compared to
      venoarterial ECMO. Eighteen New Zealand White rabbits were assigned to a control
      group (control) or two intervention groups subjected to 60 min of venoarterial or
      venovenous ECMO. ECMO was initiated following an intravenous challenge with 0.5
      mg/kg of E. coli endotoxin and a period of global hypoxia leading to an arterial
      pH of 6.99 +/- 0.09, PaCO2 of 103 +/- 31 mmHg and PaO2 of 27 +/- 5 mmHg.
      Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in lung
      tissue homogenates and in arterial plasma. Lung tissue MDA demonstrated a strong
      trend towards an increase in the venoarterial group (1884 +/- 945 nmol/g protein)
      and in the venovenous group (1905 +/- 758 nmol/g protein) in comparison to the
      control group (644 +/- 71 nmol/g protein) (p = 0.1; significance at 95% in
      Scheffe test). Lung tissue MDA in the venovenous group had a significant
      correlation with mean PaO2 during ECMO by regression analysis (r2 = 0.678, p =
      0.044). The change in blood MDA concentration between pre-ECMO and post-ECMO
      values was greater in the venovenous group (pre 1.62 +/- 0.61 versus post 5.12 +/
      0.2.07 mumol/l, p = 0.043) compared with that seen in the venoarterial group
      (pre 1.46 +/- 0.38 versus post 3.9 +/- 0.93 mumol/l). Our data support the
      hypothesis that initiation of ECMO with a circuit gas oxygen concentration of
      100% after global hypoxia enhances oxidative damage to lipids in endotoxin
      challenged animals. During venovenous ECMO this finding is dependent on PaO2.

PMID- 10074648
TI  - Optimized performance of the Abiomed BVS 5000: adjustment of the pump height
      based on Doppler control of the flow pattern.
AB  - The Abiomed BVS 5000 is an automatic volume-driven paracorporeal pulsatile assist
      device providing left, right or biventricular support. The paracorporeal position
      allows optical adjustment of filling volumes of the device, which determines the
      output of the system. A procedure to adjust for maximal stable flow has not yet
      been established. In vitro measurements have been performed to assess the flow
      and pressure characteristics of the Abiomed BVS 5000 by raising the preload in 5
      mmHg steps before running the system. Doppler probes were placed at the inflow
      and outflow lines of the pump. After setting the afterload at 80 mmHg the assist
      device was started. Two measurements were performed to find optimal flow (based
      on Doppler control and optical adjustment). (1) By Doppler control a stable flow
      pattern was found at a preload of 25 mmHg with a mean atrial pressure of 5 mmHg
      and a mean flow of 5.3 +/- 0.7 l/min (mean +/- standard deviation) at the inflow
      and outflow sites (the console flow was 4.8 +/- 0.4 l/min with a frequency of
      61.8 +/- 2.0 l/min). (2) Optical adjustment of the pump height gave rise to a
      preload of 35 mmHg where we recorded a maximal atrial pressure of 107 +/- 5.8
      mmHg, a maximal retrograde flow of -4.3 +/- 1.2 l/min at the inflow and -1.2 +/-
      0.4 l/min at the outflow site. The mean flow at the inflow and outflow sites was
      5.1 +/- 0.5 l/min (the console flow was 4.6 +/- 0.3 l/min with a frequency of
      59.6 +/- 2.6 Hz). At an initial afterload of 60 and 40 mmHg the system showed the
      same qualitative behaviour, but the results were less accurate. Optical
      adjustment of the pump height may result in an atrioventricular valve
      insufficiency with undetected retrograde flow and high atrial pressures. We
      conclude that a Doppler flow probe must be placed at the inflow site to guarantee
      maximal stable flow.

PMID- 10074649
TI  - Venous saturation monitoring: reliability of the Bentley SM-0200 OxySAT with and
      without use of a cuvette.
AB  - In-line venous saturation monitoring is a useful method of quality management
      during extracorporeal circulation (ECC). The Bentley SM-0200 OxySAT meter was
      tested with and without the use of the recommended cuvette. The study consisted
      of an in vitro part, where extremely low saturations could be safely measured,
      and an in vivo part, carried out under routine ECC conditions. The results show
      that the OxySAT may be used with or without a cuvette, and that it needs
      calibration for optimal accuracy in either case.

PMID- 10074650
TI  - Clinical experience with the Sorin Monolyth Oxygenator at high altitude.
AB  - High altitude combined with low barometric pressure can present unique challenges
      during cardiopulmonary bypass (CPB), not only for the perfusionist, but also for
      the oxygenator. Manufacturers of cardiopulmonary devices have responded to the
      requests from the perfusion community with a variety of oxygenators which balance
      low priming volumes and low pressure drops against high gas transfer. This paper
      will feature the first author's clinical studies using the Sorin Monolyth
      Oxygenator in a selected group of patients at an altitude of approximately 5200
      feet and an average barometric pressure of 634 mmHg (sea levels is 760 mmHg). A
      review of the 47 charts on patients requiring CPB and who met the selection
      criteria was performed retrospectively. To qualify for this study, the patient
      needed to weigh more than 91 kg. The data reviewed included type of surgery, age,
      weight, bypass time, crossclamp time, pump flows (l/min/m2), hematocrits pre- and
      post-CPB, and pressure drop across the membrane. The PaO2, PaCO2, FiO2 and sweep
      gas flow at hypothermia and normothermia were recorded. Data concerning oxygen
      transfer were obtained from the manufacturer's report to the Food and Drug
      Administration. All patients had adequate blood gases while on CPB. We feel that
      the design of the Sorin Monolyth Oxygenator met our criteria for an oxygenator:
      low priming volume, low pressure drop, and sufficient gas transfer to provide
      safe oxygenation of all patients at high altitude.

PMID- 10074651
TI  - Gastrointestinal malignancies. Introduction.

PMID- 10074652
TI  - Molecular genetics of gastrointestinal malignancies.
AB  - OBJECTIVES: To review the genetic model of colon cancer formation and the primary
      advances and clinical relevance of molecular genetics of pancreatic cancer and
      other gastrointestinal malignancies. DATA SOURCES: Research studies, review
      articles, and textbook chapters. CONCLUSIONS: Genetic discoveries are influencing
      the screening and treatment of colorectal cancer and other gastrointestinal
      malignancies by better targeting chemoprevention and treatment in high-risk and
      molecular-distinct patient populations. IMPLICATIONS FOR NURSING PRACTICE: A
      basic knowledge of cancer genetics and the latest genetic discoveries will assist
      oncology nurses in patient teaching, counseling, and care.

PMID- 10074653
TI  - Diagnosing gastrointestinal malignancies.
AB  - OBJECTIVES: To provide an overview of imaging studies that can be used to help
      diagnose gastrointestinal malignancies and a brief description of tumor markers
      specific for these cancers. DATA SOURCES: Published professional articles,
      textbooks, and clinical procedural manuals. CONCLUSIONS: Diagnosing
      gastrointestinal malignancies can be problematic due to the relative lack of
      signs and symptoms, especially early in the disease process. While clinical
      suspicion may lead to a tentative diagnosis, imaging studies and tumor markers
      can provide confirmation of the suspected malignancy. IMPLICATIONS FOR NURSING
      PRACTICE: An understanding of the requirements of imaging studies and tumor
      markers will allow for better preparation of the patient by the nurse for the
      test and can assist the nurse in helping the patient understand the need for and
      results of the diagnostic work-up.

PMID- 10074654
TI  - Esophageal cancer: therapeutic approaches and nursing care.
AB  - OBJECTIVES: To review the various treatment approaches, complications, and
      nursing management of patients with esophageal cancer. DATA SOURCES: Review
      articles, staging manual, textbook chapters, and research studies. CONCLUSIONS:
      The diagnosis and treatment of esophageal cancer is a complicated process.
      Combined multimodal therapy with chemotherapy, radiotherapy, and surgery is
      showing promising results. However, each treatment approach has complications and
      side effects that must be managed. IMPLICATIONS FOR NURSING PRACTICE: Nursing
      care is complicated and requires coordinating various support services, patient
      and family education, clinical assessment, nutritional management, management of
      side effects, and palliative care.

PMID- 10074655
TI  - Gastric cancer.
AB  - OBJECTIVES: To review the current status, recent advances, and ongoing research
      related to screening, diagnosis, staging, and treatment of gastric cancer. DATA
      SOURCES: Professional journals, research studies, and review articles relating to
      gastric cancer. CONCLUSIONS: Surgical resection is the gold standard curative
      treatment for gastric cancer; however, diagnosis is often at later stages of
      disease, leaving poor long-term survival rates. An emphasis has been placed on
      developing more effective chemotherapy regimens; currently, fluorouracil is the
      standard single agent used for gastric cancer. Radiation therapy has been used
      for palliative symptom management. IMPLICATIONS FOR NURSING PRACTICE: An
      understanding of current treatment modalities for gastric cancer will help
      oncology nurses assist their patients throughout their course of treatment with
      education, nutritional support, and symptom control.

PMID- 10074656
TI  - Pancreatic cancer: a continuum of care.
AB  - OBJECTIVES: To provide information about the etiology, clinical manifestations,
      treatment, and symptom management of pancreatic cancer. DATA SOURCES: Textbook
      chapters, research studies, and review articles. CONCLUSIONS: Cancer of the
      pancreas is a devastating disease. A diagnosis of pancreatic cancer causes a
      person to consider both quantity as well as quality of life. Hope for improved
      quality of life and survival relies on the efforts of a co-operative
      multidisciplinary team approach. IMPLICATIONS FOR NURSING PRACTICE: Numerous
      nursing challenges exist in providing care for the patient with pancreatic
      cancer. Treatment, symptom management, and psychological, social, and spiritual
      support are essential in meeting the needs of the patient and family through the
      eventuality of the disease.

PMID- 10074657
TI  - Primary and metastatic liver cancer.
AB  - OBJECTIVES: To review liver physiology, the disease process, diagnostic tests,
      and current treatment options for primary and metastatic liver cancer. DATA
      SOURCES: Research studies, review articles, and textbooks relating to liver
      cancer. CONCLUSIONS: Surgical resection offers the best available treatment
      modality, but only a small percentage of patients are eligible. However, combined
      treatment of radiation therapy and chemotherapy (systemic and intra-arterial), as
      well as chemoembolization, cryosurgery, and transplantation, offers hope of
      palliation, conversion of unresectable to resectable disease, and prolonged
      survival. IMPLICATIONS FOR NURSING PRACTICE: Understanding and knowledge of the
      disease process and treatment modalities for primary and metastatic liver cancer
      will assist the oncology nurse in educating patients and families during their
      diagnostic and treatment phases.

PMID- 10074658
TI  - Colorectal cancer.
AB  - OBJECTIVES: To provide a review of the etiology, risk factors, treatment, and
      nursing care of patients with colorectal cancer. DATA SOURCES: Review articles,
      screening guidelines, and textbook chapters. CONCLUSIONS: Although colorectal
      cancer remains a major health threat in the United States, advances made over the
      last 10 years in prevention, diagnosis, and treatment have changed the management
      and care of patients with this disease. The key to survival of colorectal cancer
      is screening and early detection. IMPLICATIONS FOR NURSING PRACTICE: Regardless
      of the multimodalities of treatment used, the nurse's role as educator,
      caregiver, supporter, and advocate requires an ongoing commitment to remain
      knowledgeable of and current in advances made in the prevention, detection, and
      treatment of colorectal cancer.

PMID- 10074659
TI  - Food Standards Agency: the government publishes draft legislation.

PMID- 10074660
TI  - Tonsillar lesions in cattle naturally infected with Mycobacterium bovis.
AB  - The upper respiratory tract surfaces, the palatine and pharyngeal tonsils and
      associated lymph nodes of 32 tuberculin reactor cattle were examined
      pathologically and bacteriologically. Tuberculous lesions were observed
      histologically in the palatine tonsils of five animals and in both the palatine
      and pharyngeal tonsils of a sixth. Mycobacterium bovis was cultured from the
      tonsils of four of these animals and from the palatine or pharyngeal tonsils of a
      further eight cattle in which no lesions were observed. The upper respiratory
      tract surfaces of 10 animals were M bovis-positive.

PMID- 10074661
TI  - Hepatic lipodystrophy of pedigree Galloway calves.
AB  - Hepatic lipodystrophy has been recognised in pedigree Galloway calves since 1965.
      Between 1975 and 1984 15 cases from five farms were examined. The calves
      initially appear normal and in good bodily condition but invariably die by five
      months of age. The characteristic clinical and neurological changes lead to body
      tremors, opisthotonus, and dyspnoea before the animals become recumbent and die.
      On postmortem examination the most significant finding in all cases was an
      enlarged, pale and mottled liver weighing up to 2.75 kg. Limited
      histopathological examinations of the brain and liver revealed changes suggestive
      of hepatic encephalopathy. Exhaustive investigations of the farms failed to
      reveal any significant findings and the small number of cases made it impossible
      to determine whether the disease was genetically determined; limited evidence
      suggests that a 'storage disease' cannot be excluded.

PMID- 10074662
TI  - Bovine abortion associated with Neospora caninum in northern Spain.
AB  - During 1996, aborted bovine fetuses from dairy herds in norther Spain were
      examined by histopathological, immunohistochemical and serological methods for
      evidence of infection by Neospora caninum. Microscopical brain changes consistent
      with those of neosporosis were detected in 36 of 81 fetuses and specific
      antibodies (IFAT titres > or = 1/16) in 32 of 63. Eight fetuses with neurological
      lesions were seronegative, and eight without lesions were seropositive. In 25 of
      34 fetal brains with lesions consistent with published descriptions of
      neosporosis, immunohistochemical analysis revealed the presence of N caninum
      antigen. Depending on the diagnostic criteria, the prevalence of neosporosis
      related to bovine abortion was between 32 and 57 per cent of the fetuses
      submitted and between 33 and 58 per cent of the herds involved. Data on the
      geographical, seasonal and fetal age distribution of the infection are given for
      the fetuses examined and the value of the different diagnostic methods is
      discussed.

PMID- 10074663
TI  - Association of non-cytopathogenic BVDV with bovine blastocysts: effects of
      washing, duration of viral exposure and degree of blastocyst expansion.

PMID- 10074664
TI  - Aujeszky's disease virus infection concurrent with postweaning multisystemic
      wasting syndrome in pigs.

PMID- 10074665
TI  - Fibroblastic osteosarcoma in a chamois (Rupicapra pyrenaica parva).

PMID- 10074666
TI  - Veterinary nurse training--changes for the better.

PMID- 10074667
TI  - EU ban on four antibiotic growth promoters.

PMID- 10074668
TI  - EU ban on four antibiotic growth promoters.

PMID- 10074669
TI  - 'Omnicompetent' graduates.

PMID- 10074670
TI  - Ear and flank biting in pigs.

PMID- 10074671
TI  - Piglet tail necrosis.

PMID- 10074674
TI  - Cognitive development: children's knowledge about the mind.
AB  - This chapter reviews theory and research on the development of children's
      knowledge about the mental world, focusing especially on work done during the
      past 15 years under the rubric of theory-of-mind development. The three principal
      approaches to explaining this development--theory theory, modular theory, and
      simulation theory--are described first. Next comes a description of infant
      precursors or protoforms of theory-of-mind knowledge in infancy, including a
      beginning awareness of the intentionality and goal-directedness of human actions.
      This discussion is followed by a summary of the postinfancy development of
      children's understanding of visual perception, attention, desires, emotions,
      intentions, beliefs, knowledge, pretense, and thinking. Briefly considered next
      are intracultural, intercultural, and interspecies differences in theory-of-mind
      development. The chapter then concludes with some guesses about the future of the
      field.

PMID- 10074675
TI  - Psychopathology: description and classification.
AB  - DSM-IV's strong empirical base has yielded an instrument with good to excellent
      reliability and improved validity. Diagnostic reliability depends on both the
      clarity and validity of diagnostic criteria and the changeability of disorders
      over time: The reliability of schizophrenic spectrum disorders, personality
      disorders, and some childhood and adolescent disorders remains problematic.
      Findings on diagnostic validity appear paradoxical: Attempts to validate
      schizophrenic spectrum disorders with neurobiological and genetic-familial
      validators have been only modestly successful, whereas the tripartite personality
      trait model has differentiated a range of depressive and anxiety disorders.
      Research on comorbidity has identified several highly comorbid disorders
      (substance-related disorders, personality disorders, depression, and anxiety) as
      well as some adverse consequences of comorbidity. The advantages of dimensional
      approaches to diagnosis have largely been demonstrated conceptually; ultimate
      conclusions about the strengths and weaknesses of dimensional and syndromal
      methods await substantial additional empirical research.

PMID- 10074676
TI  - Health psychology: mapping biobehavioral contributions to health and illness.
AB  - Our evolving understanding of how psychosocial and behavioral factors affect
      health and disease processes has been marked by investigation of specific
      relationships and mechanisms underlying them. Stress and other emotional
      responses are components of complex interactions of genetic, physiological,
      behavioral, and environmental factors that affect the body's ability to remain or
      become healthy or to resist or overcome disease. Regulated by nervous, endocrine,
      and immune systems, and exerting powerful influence on other bodily systems and
      key health-relevant behaviors, stress and emotion appear to have important
      implications for the initiation or progression of cancer, HIV, cardiovascular
      disease, and other illnesses. Health-enhancing and health-impairing behaviors,
      including diet, exercise, tobacco use, and protection from the sun, can
      compromise or benefit health and are directed by a number of influences as well.
      Finally, health behaviors related to being ill or trying to avoid disease or its
      severest consequences are important. Seeking care and adhering to medical
      regimens and recommendations for disease surveillance allow for earlier
      identification of health threats and more effective treatment. Evidence that
      biobehavioral factors are linked to health in integrated, complex ways continues
      to mount, and knowledge of these influences has implications for medical outcomes
      and health care practice.

PMID- 10074677
TI  - Interventions for couples.
AB  - A substantial body of empirical research has documented both the promise and the
      shortcomings of psychological interventions for preventing or ameliorating
      marital distress. Couple therapy reduces relationship distress and may affect
      individual psychopathology, such as depression. However, some couples are
      unresponsive and others improve but relapse later. Interventions to prevent
      marital distress usually produce short-term changes in behavior and relationship
      satisfaction, but little evidence exists demonstrating a longer-term prevention
      effect. Furthermore, these interventions have yet to be examined on a diverse
      population of couples or with a diverse set of outcome criteria (e.g. effects on
      children). Concern about the negative impact of marital discord and divorce will
      continue to provide the impetus for research on more effective means of
      intervening with couples. Future research could benefit from a focus on a more
      diverse population of couples, treatment in natural settings, the development of
      more powerful interventions, and the examination of those interventions over
      longer periods of time and with more comprehensive outcome measures.

PMID- 10074678
TI  - Emotion.
AB  - We review recent trends and methodological issues in assessing and testing
      theories of emotion, and we review evidence that form follows function in the
      affect system. Physical limitations constrain behavioral expressions and incline
      behavioral predispositions toward a bipolar organization, but these limiting
      conditions appear to lose their power at the level of underlying mechanisms,
      where a bivalent approach may provide a more comprehensive account of the affect
      system.

PMID- 10074679
TI  - High-level scene perception.
AB  - Three areas of high-level scene perception research are reviewed. The first
      concerns the role of eye movements in scene perception, focusing on the influence
      of ongoing cognitive processing on the position and duration of fixations in a
      scene. The second concerns the nature of the scene representation that is
      retained across a saccade and other brief time intervals during ongoing scene
      perception. Finally, we review research on the relationship between scene and
      object identification, focusing particularly on whether the meaning of a scene
      influences the identification of constituent objects.

PMID- 10074680
TI  - Interpersonal processes: the interplay of cognitive, motivational, and behavioral
      activities in social interaction.
AB  - This analytic review is concerned with the interpersonal processes, and the
      characteristics of situations and persons that influence them, that lead to the
      confirmation and disconfirmation of expectations in the course of social
      interaction. We examine the steps in the chain of events by which the
      expectations of one person guide and direct the dynamics of social interaction
      such that the behavior of the target of those expectations comes to confirm or
      disconfirm those expectations. We further inquire into the motivational and
      structural foundations of confirmation and disconfirmation in social interaction,
      using these inquiries to address frequently asked, but rarely answered, questions
      about expectations and social interaction. Finally, we argue that investigations
      of expectations in social interaction provide a paradigm for more general
      theoretical and empirical considerations of interpersonal processes and social
      relationships.

PMID- 10074681
TI  - Somesthesis.
AB  - In this review we focus on the perceptual and psychophysical aspects of
      somesthesis, although some information on neurophysiological aspects will be
      included as well; we look primarily at studies that have appeared since 1988. In
      the section on touch, we cover peripheral sensory mechanisms and several topics
      related to spatial and temporal pattern perception, specifically measures of
      spatial sensitivity, texture perception with particular emphasis on perceived
      roughness, complex spatial-temporal patterns, and the use of touch as a possible
      channel of communication. Other topics under this section include the effects of
      attention on processing tactile stimuli, cortical mechanisms, and the effects of
      aging on sensitivity. We also deal with thermal sensitivity and some aspects of
      haptics and kinesthesis. In the section on pain, we review work on the gate
      control theory, sensory fibers, and higher neural organization. In addition,
      studies on central neurochemical effects and psychophysics of pain are examined.

PMID- 10074682
TI  - Peer relationships and social competence during early and middle childhood.
AB  - This review demarcates major periods of empirical activity and accomplishment
      (i.e. "generations") in research on children's peer relations and social
      competence during recent decades and identifies the investigative agendas that
      were dominant or ascendant during these periods. A sampling of studies that were
      conducted during the most recent generation of peer relations research is
      organized and reviewed in relation to two types of research objectives: (a)
      enduring agendas--aims from past research generations that have continued to
      serve as an impetus for empirical investigation during the 1990s--and (b)
      innovative agendas--newly emergent objectives that are predicated on novel
      conceptual issues or ongoing research controversies and deficiencies. This
      profile of continuity and change in investigators' research agendas provides a
      platform for delineating and analyzing recent empirical accomplishments in the
      field of peer relations research.

PMID- 10074683
TI  - Social, community, and preventive interventions.
AB  - Psychology can and should be at the forefront of participation in social,
      community, and preventive interventions. This chapter focuses on selective topics
      under two general areas: violence as a public health problem and health
      promotion/competence promotion across the life span. Under violence prevention,
      discussion of violence against women, youth violence, and child maltreatment are
      the focal points. Under health and competence promotion, attention is paid to the
      prevention of substance abuse and HIV/AIDS. We highlight a few significant
      theoretical and empirical contributions, especially from the field of
      community/prevention psychology. The chapter includes a brief overview of
      diversity issues, which are integral to a comprehensive discussion of these
      prevention efforts. We argue that the field should extend its role in social
      action while emphasizing the critical importance of rigorous research as a
      component of future interventions.

PMID- 10074684
TI  - The suggestibility of children's memory.
AB  - In this review, we describe a shift that has taken place in the area of
      developmental suggestibility. Formerly, studies in this area indicated that there
      were pronounced age-related differences in suggestibility, with preschool
      children being particularly susceptible to misleading suggestions. The studies on
      which this conclusion was based were criticized on several grounds (e.g.
      unrealistic scenarios, truncated age range). Newer studies that have addressed
      these criticisms, however, have largely confirmed the earlier conclusions. These
      studies indicate that preschool children are disproportionately vulnerable to a
      variety of suggestive influences. There do not appear to any strict boundary
      conditions to this conclusion, and preschool children will sometimes succumb to
      suggestions about bodily touching, emotional events, and participatory events.
      The evidence for this assertion is presented in this review.

PMID- 10074685
TI  - Individual psychotherapy outcome and process research: challenges leading to
      greater turmoil or a positive transition?
AB  - Psychotherapy is facing challenges that relate to the emergence of managed health
      care, the possibility of a national health care system, and advances in
      biological psychiatry. These situations have created pressure to achieve a more
      accurate assessment of psychotherapeutic effectiveness. Psychotherapy has been
      proven to be generally effective; however, there is uncertainty as to why. The
      field is currently experiencing apparent turmoil in three areas: (a) theory
      development for psychotherapeutic effectiveness, (b) research design, and (c)
      treatment technique. This chapter reviews the dynamics within each of the areas
      and highlights the progress made in treating mental disorders. We conclude that
      recent advances in research design may provide a transition that will bring
      psychotherapy closer to becoming a unified paradigm with an acceptable theory of
      effectiveness.

PMID- 10074686
TI  - Influences on infant speech processing: toward a new synthesis.
AB  - To comprehend and produce language, we must be able to recognize the sound
      patterns of our language and the rules for how these sounds "map on" to meaning.
      Human infants are born with a remarkable array of perceptual sensitivities that
      allow them to detect the basic properties that are common to the world's
      languages. During the first year of life, these sensitivities undergo
      modification reflecting an exquisite tuning to just that phonological information
      that is needed to map sound to meaning in the native language. We review this
      transition from language-general to language-specific perceptual sensitivity that
      occurs during the first year of life and consider whether the changes propel the
      child into word learning. To account for the broad-based initial sensitivities
      and subsequent reorganizations, we offer an integrated transactional framework
      based on the notion of a specialized perceptual-motor system that has evolved to
      serve human speech, but which functions in concert with other developing
      abilities. In so doing, we highlight the links between infant speech perception,
      babbling, and word learning.

PMID- 10074687
TI  - Single-gene influences on brain and behavior.
AB  - As traditional behavioral genetics analysis merges with neurogenetics, the field
      of neurobehavioral genetics, focusing on single-gene effects, comes into being.
      New biotechnology has greatly accelerated gene discovery and the study of gene
      function in relation to brain and behavior. More than 7,000 genes in mice and
      10,000 in humans have now been documented, and extensive information about the
      genetics of several species is readily available on the World Wide Web. Based on
      knowledge of the DNA sequence of a gene, a targeted mutation with the capacity to
      disable it can be created. These knockouts--also called null mutants--are
      employed in the study of a wide range of phenotypes, including learning and
      memory, appetite and obesity, and circadian rhythms. The era of examining single
      gene effects from a reductionistic perspective is waning, and research with
      interacting arrays of genes in various environmental contexts is demonstrating a
      need for systems-oriented theory.

PMID- 10074688
TI  - Neuroethology of spatial learning: the birds and the bees.
AB  - The discipline of neuroethology integrates perspectives from neuroscience,
      ethology, and evolutionary biology to investigate the mechanisms underlying the
      behavior of animals performing ecologically relevant tasks. One goal is to
      determine if common organizational principles are shared between nervous systems
      in diverse taxa. This chapter selectively reviews the evidence that particular
      brain regions subserve behaviors that require spatial learning in nature. Recent
      evidence suggests that the insect brain regions known as the mushroom bodies may
      function similarly to the avian and mammalian hippocampus. Volume changes in
      these brain regions during the life of an individual may reflect both
      developmental and phylogenetic trends. These patterns may reveal important
      structure-function relationships in the nervous system.

PMID- 10074689
TI  - Dependence of peripheral tremor on mechanical perturbations: a modeling study.
AB  - The present study scrutinizes the popular view that tremors of central origin but
      not those of peripheral origin are largely resistant to mechanical perturbations.
      We explore the effects of perturbations in a well-established model of peripheral
      tremor and document that (a) tremor frequency can remain unchanged when spring or
      weight loads are added, (b) entrainment by external drives can be limited to
      drives of similar frequency, and (c) resetting of tremor phase by torque pulses
      can remain fractional. This resistance to mechanical perturbations arises in the
      model because peripheral neuromuscular dynamics act as a limit-cycle oscillator
      which, by its very nature, will absorb moderate changes to signals and
      parameters. We conclude from our study that resistance to mechanical
      perturbations is not an exclusive property of central tremors, but rather may
      also be found in peripheral tremors. Other criteria are therefore needed to
      distinguish between different origins of tremor.

PMID- 10074690
TI  - Cortical hypercolumn size determines stereo fusion limits.
AB  - The size of a pair of cortical ocular dominance columns determines a basic
      anatomical module of V-1 which Hubel and Wiesel have termed the hypercolumn. Does
      this correspond to a basic functional, or psychophysically measurable, module as
      well? This is the basic question addressed in the present paper. Since the ocular
      dominance column architecture is presumed to be related to stereo vision, it is
      natural to assume that hypercolumn size should provide a modular basis for basic
      phenomena of stereopsis. In previous work, we have suggested that local nonlinear
      filtering via the cepstral transform, operating on a local window of cortical
      tissue scaled by hypercolumn size, provides such a modular model of stereopsis.
      In the present paper, we review this model and then discuss a number of issues
      related to the biological plausibility and implementation of this algorithm.
      Then, we present the main result of this paper: we have analyzed a number of
      experiments related to stereo fusion limits (Panum's area) and to disparity
      gradient and disparity scaling, and demonstrate that there is a simple unifying
      explanation for these phenomena in terms of a constant cortical module whose size
      is determined by a pair of ocular dominance columns. As a corollary, Panum's area
      must increase according to (inverse) cortical magnification factor. We show that
      this is supported by all existing experimental data.

PMID- 10074691
TI  - The statistical relationship between connectivity and neural activity in
      fractionally connected feed-forward networks.
AB  - It is desirable to have a statistical description of neuronal connectivity in
      developing tractable theories on the development of biological neural networks
      and in designing artificial neural networks. In this paper, we bring out a
      relationship between the statistics of the input environment, the degree of
      network connectivity, and the average postsynaptic activity. These relationships
      are derived using simple neurons whose inputs are only feed-forward, excitatory
      and whose activity is a linear function of its inputs. In particular, we show
      that only the empirical mean of the pairwise input correlations, rather than the
      full matrix of all such correlations, is needed to produce an accurate estimate
      of the number of inputs necessary to attain a prespecified average postsynaptic
      activity level. Predictions from this work also include distributional aspects of
      connectivity and activity as shown by a combination of analysis and simulations.

PMID- 10074692
TI  - Simulation of atrial activity by a phase response curve based model of a two
      dimensional pacemaker cells array: the transition from a normal activation
      pattern to atrial fibrillation.
AB  - In this paper, we present an original model of the atria, based on our hypothesis
      that atrial cells have features of pacemaker cells, characterized by their
      normally longer intrinsic cycle lengths and different type of connection
      (stronger) than the, sino-atrial (SA) node pacemaker cells. The atrium is
      simulated by a two-dimensional array of pacemaker cells (25 x 25), composed of a
      region of SA node pacemaker cells (11 x 11) surrounded by atrial pacemaker cells.
      All pacemakers cells are characterized by only the most relevant functional
      properties, those which play the most direct role in the determination of the
      cardiac rate and in the mechanism of arrhythmias. These properties are: the
      intrinsic cycle length, tau, an 'internal' feature of each pacemaker cell, and
      the phase-response curve (PRC), an 'overall collective' function. The PRC
      embodies the interactions of each pacemaker cell with its neighboring cells, and
      thus represents the type of connection (strong, weak, etc.) of the pacemaker cell
      with its surroundings. In our model, the SA node region differs from the atrial
      region by cycle length distribution and PRCs. We studied the spatial interaction
      between SA node pacemaker cells and atrial pacemaker cells as a function of the
      regional variation of cells properties and as a function of the "electrical"
      coupling between cells (the PRC), in the SA node region, in the atrial region,
      and in a border zone between them. We investigated the influence of those
      parameters on the activation pattern, on the conduction time of the array, and on
      a pseudo-ECG signal. This study demonstrates that by representing the atrial
      cells as a population of 'pacemaker-like' cells, similar to the SA node pacemaker
      cells, but differing markedly in their cycle lengths and cell-to-cell interaction
      (PRC), we can create a global picture of the atrial system by applying a simple
      physical-mathematical model. This approach enables us to explore physiological
      phenomena related to the genesis and maintenance of atrial activity. It also
      reveals the conditions which predispose to atrial arrhythmias and conduction
      disturbances (e.g. tachycardia, pacemaker shift, re-entry, fibrillation). In
      particular, it yields insight into the mechanism of transition from normal atrial
      activity to the disordered state of atrial fibrillation. Therefore, this study
      suggests a new way of looking at the development of cardiac arrhythmias of atrial
      origin.

PMID- 10074693
TI  - Interactions of alpha-helices with lipid bilayers: a review of simulation
      studies.
AB  - Membrane proteins, of which the majority seem to contain one or more alpha-helix,
      constitute approx. 30% of most genomes. A complete understanding of the nature of
      helix/bilayer interactions is necessary for an understanding of the structural
      principles underlying membrane proteins. This review describes computer
      simulation studies of helix/bilayer interactions. Key experimental studies of the
      interactions of alpha-helices and lipid bilayers are briefly reviewed. Surface
      associated helices are found in some membrane-bound enzymes (e.g. prostaglandin
      synthase), and as stages in the mechanisms of antimicrobial peptides and of pore
      forming bacterial toxins. Transmembrane alpha-helices are found in most integral
      membrane proteins, and also in channels formed by amphipathic peptides or by
      bacterial toxins. Mean field simulations, in which the lipid bilayer is
      approximated as a hydrophobic continuum, have been used in studies of membrane
      active peptides (e.g. alamethicin, melittin, magainin and dermaseptin) and of
      simple membrane proteins (e.g. phage Pf1 coat protein). All atom molecular
      dynamics simulations of fully solvated bilayers with transmembrane helices have
      been applied to: the constituent helices of bacteriorhodopsin; peptide-16 (a
      simple model TM helix); and a number of pore-lining helices from ion channels.
      Surface associated helices (e.g. melittin and dermaseptin) have been simulated,
      as have alpha-helical bundles such as bacteriorhodopsin and alamethicin. From
      comparison of the results from the two classes of simulation, it emerges that a
      major theoretical challenge is to exploit the results of all atom simulations in
      order to improve the mean field approach.

PMID- 10074694
TI  - Determination of carbaryl, carbofuran and methiocarb in cucumbers and
      strawberries by monoclonal enzyme immunoassays and high-performance liquid
      chromatography with fluorescence detection. An analytical comparison.
AB  - Carbaryl, carbofuran and methiocarb are three of the most important N
      methylcarbamate pesticides. In the present work, the application of laboratory
      developed monoclonal antibody-based enzyme-linked immunosorbent assays (ELISAs)
      to the determination of these compounds in fruits and vegetables is described.
      Cucumbers and strawberries were spiked with the three carbamates at 10, 50 and
      200 ppb. After extraction and clean-up, samples were analyzed by immunoassay and
      by HPLC with post-column derivatization and fluorescence detection (US
      Environmental Protection Agency Method 531.1). Results obtained by ELISA
      correlated well with those obtained by HPLC, both in terms of accuracy and
      precision. Recoveries were in the 60-90% range by ELISA and in the 50-90% range
      by HPLC, depending on the particular combination of commodity, pesticide, and
      fortification level under consideration. ELISAs were also applied to the analysis
      of non-purified sample extracts with excellent results: recoveries close to 100%
      were obtained, while maintaining similar precision values. This approach avoids
      the use of solid-phase extraction columns, saves time, and considerably increases
      the sample throughput. Results clearly indicate that the developed immunoassays
      may be suitable for the quantitative and reliable determination of carbaryl,
      carbofuran and methiocarb in fruits and vegetables even without including clean
      up steps. These considerations make these ELISAs very useful analytical tools for
      monitoring and regulatory programs, without the need of complex and expensive
      instrumentation.

PMID- 10074695
TI  - Determination of abamectin residues in fruits and vegetables by high-performance
      liquid chromatography.
AB  - A rapid and sensitive HPLC method has been developed and validated for the
      determination of abamectin residues (avermectin B1a and B1b, as well as the
      metabolite 8,9-Z-avermectin B1) in apples, pears and tomatoes. Residues are
      extracted with acetonitrile. The diluted extract is cleaned up on a C18 solid
      phase extraction cartridge. Abamectin residues are derivatised with
      trifluoroacetic acid and 1-methylimidazole and determined by reversed-phase
      liquid chromatography with fluorescence detection (excitation: 365 nm and
      emission: 470 nm). High and consistent recoveries, ranging from 88 to 106%, were
      obtained, at spiking levels of 10, 20 and 50 micrograms/kg, when analysing
      apples, pears and tomatoes.

PMID- 10074696
TI  - Determination of pyrethroid pesticide residues in fatty materials by solid-matrix
      dispersion partition, followed by mini-column size-exclusion chromatography.
AB  - The method studied uses a combination of a solid-matrix dispersion partition
      (SMDP) followed by high-performance size-exclusion chromatography on a minicolumn
      (HPmSEC) of 7.8 mm I.D. for the separation of pyrethroid (PYR) residues from
      fatty material. The solid-matrix dispersion extraction is carried out by
      absorbing a fat solution onto an Extrelut-3 cartridge (filled with a macroporous
      diatomaceous material) and extracting the PYR residues with acetonitrile. Up to 1
      g of fatty material can be extracted with 15 ml acetonitrile. The small amount
      (mean +/- S.D. = 12.4 +/- 5.9 mg) of fatty material which is eluted into the
      acetonitrile is further removed by HPmSEC. PYR pesticide residues are collected
      in a 2-ml fraction between 7 and 9 ml, the column being washed up to 24 ml. The
      two techniques used in series allow a better removal of fat, a greater input of
      sample and a lower consumption of solvent compared to the sole SEC on
      macrocolumns, and a lower limit of determination compared to the sole SEC on
      minicolumns. Recoveries of 9 PYR out of the 14 investigated residues from soya
      oil were in the range 66-83% at spiking levels ranging 0.49-2.57 mg/kg, while for
      6 PYR residues tested at spiking levels in the range 0.13-0.53 mg/kg the
      recoveries were in the range 80-111%. Recovery of fluvalinate and permethrin
      could not be calculated due to interferences from soya oil, while lambda
      cyhalothrin, esfenvalerate and tralomethrin gave low recovery. The final extract
      contains small amount (mean +/- S.D. = 2.4 +/- 0.9 mg) of lipid residue and is
      not completely free from interferences.

PMID- 10074697
TI  - Validation of a solid-phase microextraction method for the determination of
      organophosphorus pesticides in fruits and fruit juice.
AB  - A method for the determination of organophosphorus pesticides (diazinon,
      fenitrothion, fenthion, quinalphos, triazophos, phosalon and pyrazophos) in fruit
      (pears) and fruit juice samples was developed and validated. The samples were
      diluted with water, extracted by solid-phase microextraction (SPME) and analysed
      by gas chromatography (GC) using a flame photometric detector in phosphorous
      mode. Limits of detection of the method for fruit and fruit juice matrices were
      below 2 micrograms/kg for all pesticides. Relative standard deviations for
      triplicate analyses of samples fortified at 25 micrograms/kg of each pesticide
      were not higher than 8.7%. Recovery tests were performed for concentrations
      between 25 and 250 micrograms/kg. Mean recoveries for each pesticide were all
      above 75.9% and below 102.6% for juice, and between 70 and 99% for fruit except
      for pyrazophos in the fruit sample (with mean recovery of 53%). Therefore, the
      proposed method is applicable in the analysis of pesticides in fruit matrices and
      the use of the method in routine analysis of pesticide residues is discussed.

PMID- 10074698
TI  - Determination of chlorpyrifos, penconazole, fenarimol, vinclozolin and metalaxyl
      in grapes, must and wine by on-line microextraction and gas chromatography.
AB  - A rapid gas chromatographic method for determination of residue levels of one
      insecticide (chlorpyrifos) and four fungicides (penconazole, fenarimol,
      vinclozolin and metalaxyl) in grapes, must and wine is described. An on-line
      microextraction method was used. The matrix, once extracted with a mixture of
      acetone-dichloromethane (1:1, v/v) was filtered and concentrated. Electron
      capture detection for chlorpyrifos, penconazole, fenarimol and vinclozolin and
      mass-selective detection in the selected-ion monitoring mode for metalaxyl were
      utilised. No clean-up was necessary because there were no interferences in the
      area of interest of the chromatogram. Linearity of both detectors, in the range
      0.02-2 ng/microliter, was checked. In all cases, the correlation coefficient was
      the same or superior to 0.997. Recoveries from spiked grapes, must and wine
      ranged from 78% to 101% (fortification level, 0.1-1 mg/kg). Limits of
      determination were between 0.01 mg/kg for metalaxyl and 0.001 mg/kg for
      vinclozolin.

PMID- 10074699
TI  - Determination of daminozide in apples and apple leaves by liquid chromatography-
      mass spectrometry.
AB  - A straightforward and efficient method was developed for the determination of
      intact daminozide in apples and apple leaves. After extraction with methanol and
      a clean-up step using a graphitized carbon cartridge, the extract was analysed by
      ion-trap liquid chromatography-tandem mass spectrometry (LC-MS-MS) using
      atmospheric pressure chemical ionisation in the positive ion mode. Recoveries for
      apple were 98-102% with a R.S.D. < or = 11% (n = 6) and for leaves were 112-116%
      with a R.S.D. < or = 18% (n = 6). The limits of detection were 0.008 and 0.02
      mg/kg for apples and leaves, respectively.

PMID- 10074700
TI  - Selective clean-up applicable to aqueous acetone extracts for the determination
      of carbendazim and thiabendazole in fruits and vegetables by high-performance
      liquid chromatography with UV detection.
AB  - Fungicide residues in vegetables (benomyl, carbendazim, thiabendazole) are
      analyzed through a clean-up procedure that uses a portion of the aqueous acetone
      extract prepared for multiresidue methodology. A portion of the aqueous acetone
      extract (equivalent to 5 g of vegetables) is loaded onto an Extrelut-20 cartridge
      (the cartridge is filled with a coarse, large-pore diatomaceous material). Then,
      acetone is partially removed by an upward stream of nitrogen at 2l/min for 30
      min. Benzimidazolic fungicides are recovered by percolating the cartridge with
      100 ml of 0.1 M phosphoric acid solution, which also serves to convert benomyl to
      carbendazim. The percolating acid solution is drained on-line through a strong
      cation-exchange (SCX) solid-phase extraction cartridge with the aid of a slight
      vacuum. Benzimidazolic fungicides are retained on the SCX cartridge. The
      phosphoric acid solution is discarded together with the washings of the SCX
      cartridge, i.e., water followed by methanol-water (75:25), that remove unwanted
      coextractives. Finally, benzimidazolic fungicides are recovered by eluting the
      SCX cartridge with methanol-ammonium formate buffer (75:25). The final extract is
      then analyzed by reversed-phase HPLC with UV detection. Recoveries from crops
      such as apples, lettuce, strawberries and citrus fruits are generally greater
      than 80% and no interferences were observed. The clean-up is simple and
      straightforward, requires only disposable items, water solutions and a few
      milliliters of solvent and a minimum number of manipulations, and does not
      require concentration steps or electrical equipment.

PMID- 10074701
TI  - Rapid determination of glyphosate in cereal samples by means of pre-column
      derivatisation with 9-fluorenylmethyl chloroformate and coupled-column liquid
      chromatography with fluorescence detection.
AB  - A rapid procedure for the determination of glyphosate in cereals has been
      developed. Convenient sample pretreatment is carried out by (i) a overnight
      standing extraction of 1.0 g homogenized sample with 20 ml of water, (ii)
      centrifugation of the samples, (iii) a passing of 2.5 ml of the clear layer
      through a 100 mg C18 solid-phase extraction cartridge and (iv) collection of the
      last 1.5 ml of the eluent into a calibrated tube. For the instrumental analysis,
      the efficient approach developed earlier for environmental water samples [J.V.
      Sancho, F. Hernandez, F.J. LUpez, E.A. Hogendoorn, E. Dijkman, P. van Zoonen, J.
      Chromatogr. A, 737 (1996) 75] was successfully adopted for the determination of
      glyphosate in the obtained cereal extracts. The procedure includes a 15 min
      derivatisation step of the analyte with 9-fluorenylmethyl chloroformate and a 16
      times dilution step prior to instrumental analysis employing coupled-column LC
      with fluorescence detection. The developed procedure has a sample throughput of
      more than 25 samples per day and a limit of quantification of 0.5 mg/kg. The
      method was validated by analyzing freshly spiked cereal samples and samples with
      aged residues at levels between 1.0 and 10 mg/kg. The overall recovery of the
      freshly spiked samples was 86% (n = 10) with a repeatability of 6.5% and a
      reproducibility of 9.5%. For samples with aged residues recoveries performed at
      different time intervals (range 80-150 days) did not differ significantly; the
      overall recovery (n = 10) was 74% with a repeatability and reproducibility of 14
      and 20%, respectively.

PMID- 10074702
TI  - Determination of dissociation constants of 99mTechnetium radiopharmaceuticals by
      capillary electrophoresis.
AB  - Capillary electrophoresis was applied to investigate pKa values of 99mTc
      radiotracers used in nuclear medicine. Therefore, the protonation equilibria of
      the carboxyl groups of 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3) and
      99mTc-ethylenecysteine dimer (99mTc-EC) were studied by pH-dependent
      determination of electrophoretical velocities. 99mTc-ethylenecysteine dimer
      diethyl ester (99mTc-ECD) was used as a non-protonable standard. The capillary
      electrophoresis system was equipped with a radioactivity detector. Measurements
      were performed using a pressure-driven capillary zone electrophoresis which
      allowed runs even in the low pH range. For the determination of pKa values, the
      electrophoretical velocities of the analytes were referred to the
      electrophoretical velocities of tetraphenyle arsonium chloride as a positively
      charged marker. Calculation of pKa values was accomplished by non-linear curve
      fitting of both structure-based equilibria equations and sigmoidal decay
      functions to the experimental data. 99mTc-MAG3 was shown to have a carboxyl group
      pKa value of 4.22. The value for the carboxyl groups of 99mTc-EC is 2.90
      (determined by structure-based equilibria equations), which represents a common
      value for both carboxyl groups. By the use of sigmoidal functions, similar values
      were elucidated. As expected, 99mTc-ECD shows no protonation step.

PMID- 10074703
TI  - Determination of the antifouling agent zinc pyrithione in water samples by copper
      chelate formation and high-performance liquid chromatography-atmospheric pressure
      chemical ionisation mass spectrometry.
AB  - Zinc pyrithione has recently been incorporated into antifouling paints as a
      booster biocide, which is slowly released into the water as the paint ages. In
      order to determine concentrations of zinc pyrithione (ZPT) in aqueous samples, a
      liquid chromatographic method has been developed. Since ZPT interacts with
      certain reversed-phase packing materials or stainless steel components of the
      HPLC system, the method uses transchelation of the ZPT into the stable copper(II)
      complex before analysis by liquid chromatography coupled to atmospheric pressure
      chemical ionisation mass spectrometry. ZPT was extracted as copper pyrithione
      using dichloromethane with adequate recovery (77% +/- 17%, n = 6) from 2-l water
      samples. The limit of detection was calculated to be 20 ng/l, using selected ion
      monitoring. The analysis of samples collected from various UK marinas showed no
      detectable concentrations to be present, whilst a laboratory-based study
      confirmed that this is probably due to the rapid photodegradation of ZPT in
      seawater.

PMID- 10074704
TI  - Perceiving individuals and groups: expectancies, dispositional inferences, and
      causal attributions.
AB  - Two experiments investigated differences in forming impressions of individual and
      group targets. Experiment 1 showed that when forming an impression of an
      individual, perceivers made more extreme trait judgments, made those judgments
      more quickly and with greater confidence, and recalled more information than when
      the impression target was a group. Experiment 2 showed that when participants
      were forming an impression of an individual, expectancy-inconsistent behaviors
      spontaneously triggered causal attributions to resolve the inconsistency; this
      was not the case when the impression target was a group. Results are interpreted
      as reflecting perceivers' a priori assumptions of unity and coherence in
      individual versus group targets.

PMID- 10074705
TI  - Tales of the unexpected: executive function and person perception.
AB  - The present research investigated the role of executive functioning in person
      perception. Given the assumption that perceivers' recollective preference for
      unexpected material relies on the operation of an executive cognitive process
      (i.e., inconsistency resolution), it was anticipated that only under dual-task
      conditions in which executive functioning is impaired would one expect
      inconsistency resolution to be impaired and perceivers' memory bias for
      unexpected material to be eliminated. When concurrent mental activity impairs the
      operation of nonexecutive cognitive operations, inconsistency resolution and the
      related process of individuation were not expected to be impaired. The results of
      2 experiments using different memory measures (e.g., free recall and source
      identification) supported these predictions. The findings are considered in the
      context of contemporary issues in person perception and executive functioning.

PMID- 10074706
TI  - Increasing the salience of one's best selves can undermine inspiration by
      outstanding role models.
AB  - The accessibility of people's highest hopes and achievements can affect their
      reactions to upward comparisons. Three studies showed that, under normal
      circumstances, individuals were inspired by an outstanding role model; their
      motivation and self-evaluations were enhanced. However, when their most positive
      self-views were temporarily or chronically activated, inspiration was undermined,
      and individuals' motivation and self-evaluations tended to decrease. Another
      study found that role models inspired participants to generate more spectacular
      hopes and achievements than they would have generated otherwise. It appears that
      increasing the accessibility of one's best selves undercuts inspiration because
      it constrains the positivity of the future selves one may imagine and prevents
      one from generating the more spectacular future selves that the role model
      normally inspires.

PMID- 10074707
TI  - Strategies to cope with negative social identity: predictions by social identity
      theory and relative deprivation theory.
AB  - Predictions by social identity theory (SIT) and relative deprivation theory (RDT)
      concerning preferences for strategies to cope with a negative in-group status
      position were tested. The focus of the present research was a comparison of the
      theories regarding their differential patterns of prediction. For this purpose, a
      natural sample within a specific historical situation was investigated: East
      Germans after the German unification. First, the predictive power of SIT and RDT
      variables was tested separately. In a second step, a possible integration of the
      theories was addressed. Combining the SIT variables and RDT variables led to an
      integrated model indicating a differential pattern of prediction for intergroup
      strategies. The RDT components explained the collective responses, whereas SIT
      constructs were related to individual strategies.

PMID- 10074708
TI  - Self-efficacy pathways to childhood depression.
AB  - This prospective research analyzed how different facets of perceived self
      efficacy operate in concert within a network of sociocognitive influences in
      childhood depression. Perceived social and academic inefficacy contributed to
      concurrent and subsequent depression both directly and through their impact on
      academic achievement, prosocialness, and problem behaviors. In the shorter run,
      children were depressed over beliefs in their academic inefficacy rather than
      over their actual academic performances. In the longer run, the impact of a low
      sense of academic efficacy on depression was mediated through academic
      achievement, problem behavior, and prior depression. Perceived social inefficacy
      had a heavier impact on depression in girls than in boys in the longer term.
      Depression was also more strongly linked over time for girls than for boys.

PMID- 10074709
TI  - "If I had it to do over again...": midlife review, midcourse corrections, and
      women's well-being in midlife.
AB  - Regrets about early adult life choices, expressed in midlife, are examined as a
      source of motivation for life changes in later midlife in 2 samples of women.
      Replicated findings with longitudinal data indicate that regret motivates goal
      setting but is not associated with actually making desired life changes. In both
      samples, women who had regrets about early adult life choices but did not make
      relevant life changes were lower in later well-being than both women with regrets
      who did make such changes and women without regrets. Compared with women who
      transformed regrets into life changes, women who did not were lower in effective
      instrumentality and higher in rumination, though they did not appear to face more
      barriers to change. Analyses with longitudinal data indicated that both
      rumination and effective instrumentality mediated the relationship between regret
      and well-being for women who did not translate regret into life changes.

PMID- 10074710
TI  - Private self-consciousness and the five-factor model of personality:
      distinguishing rumination from reflection.
AB  - A distinction between ruminative and reflective types of private self
      attentiveness is introduced and evaluated with respect to L. R. Goldberg's (1982)
      list of 1,710 English trait adjectives (Study 1), the five-factor model of
      personality (FFM) and A. Fenigstein, M. F. Scheier, and A. Buss's (1975) Self
      Consciousness Scales (Study 2), and previously reported correlates and effects of
      private self-consciousness (PrSC; Studies 3 and 4). Results suggest that the PrSC
      scale confounds two unrelated, motivationally distinct dispositions--rumination
      and reflection--and that this confounding may account for the "self-absorption
      paradox" implicit in PrSC research findings: Higher PrSC scores are associated
      with more accurate and extensive self-knowledge yet higher levels of
      psychological distress. The potential of the FFM to provide a comprehensive
      framework for conceptualizing self-attentive dispositions, and to order and
      integrate research findings within this domain, is discussed.

PMID- 10074711
TI  - KCS1 encodes a fatty acid elongase 3-ketoacyl-CoA synthase affecting wax
      biosynthesis in Arabidopsis thaliana.
AB  - An Arabidopsis fatty acid elongase gene, KCS1, with a high degree of sequence
      identity to FAE1, encodes a 3-ketoacyl-CoA synthase which is involved in very
      long chain fatty acid synthesis in vegetative tissues, and which also plays a
      role in wax biosynthesis. Sequence analysis of KCS1 predicted that this synthase
      was anchored to a membrane by two adjacent N-terminal, membrane-spanning domains.
      Analysis of a T-DNA tagged kcs1-1 mutant demonstrated the involvement of the KCS1
      in wax biosynthesis. Phenotypic changes in the kcs1-1 mutant included thinner
      stems and less resistance to low humidity stress at a young age. Complete loss of
      KCS1 expression resulted in decreases of up to 80% in the levels of C26 to C30
      wax alcohols and aldehydes, but much smaller effects were observed on the major
      wax components, i.e. the C29 alkanes and C29 ketones on leaves, stems and
      siliques. In no case did the loss of KCS1 expression result in complete loss of
      any individual wax component or significantly decrease the total wax load. This
      indicated that there was redundancy in the elongase KCS activities involved in
      wax synthesis. Furthermore, since alcohol, aldehyde, alkane and ketone levels
      were affected to varying degrees, involvement of the KCS1 synthase in both the
      decarbonylation and acyl-reduction wax synthesis pathways was demonstrated.

PMID- 10074712
TI  - Molecular and cytogenetic characterization of a transgene locus that induces
      silencing and methylation of homologous promoters in trans.
AB  - One type of homology-dependent gene silencing in transgenic plants involves a
      silencing locus that is able to transcriptionally inactivate and methylate an
      unlinked target locus with which it shares sequence identity in promoter regions.
      In a manner resembling paramutation of endogenous genes, the target locus
      reactivates and loses methylation progressively over several generations after
      segregating away from the silencing locus, which autonomously acquires stable
      methylation. To investigate the origins of trans-silencing ability and
      susceptibility, we have analyzed the structures, flanking DNA sequences and
      chromosomal locations of a nopaline synthase promoter silencing locus, H2, and a
      sensitive target locus, K81. A partially resistant target locus, K alpha has been
      characterized molecularly. The complex and scrambled H2 locus comprises six
      copies of the nopaline synthase promoter, two of which are collinear with
      prokaryotic non-T-DNA sequences, and is integrated close to a region of
      intercalary heterochromatin. These features probably contribute collectively to
      the silencing ability because H2 subclones reintroduced into random locations in
      the K81 genome did not frequently induce silencing. Both the K81 and K alpha loci
      have simple structures, although the former contains non-T-DNA prokaryotic
      sequences that are also present at H2, and they are flanked by low copy plant
      DNA. H2 and K81 might interact effectively because they are present on
      morphologically similar chromosomes from the T subgenome of allotetraploid
      tobacco.

PMID- 10074713
TI  - Sequences within both the N- and C-terminal domains of phytochrome A are required
      for PFR ubiquitination and degradation.
AB  - Photoconversion of the plant photoreceptor phytochrome A (phyA) from its inactive
      Pr form to its biologically active Pfr from initiates its rapid proteolysis.
      Previous kinetic and biochemical studies implicated a role for the ubiquitin/26S
      proteasome pathway in this breakdown and suggested that multiple domains within
      the chromoprotein are involved. To further resolve the essential residues, we
      constructed a series of mutant PHY genes in vitro and analyzed the Pfr-specific
      degradation of the resulting photoreceptors expressed in transgenic tobacco. One
      important site is within the C-terminal half of the polypeptide as its removal
      stabilizes oat phyA as Pfr. Within this half is a set of conserved lysines that
      are potentially required for ubiquitin attachment. Substitution of these lysines
      did not prevent ubiquitination or breakdown of Pfr, suggesting either that they
      are not the attachment sites or that other lysines can be used in their absence.
      A small domain just proximal to the C-terminus is essential for the form
      dependent breakdown of the holoprotein. Removal of just six amino acids in this
      domain generated a chromoprotein that was not rapidly degraded as Pfr. Using
      chimeric photoreceptors generated from potato PHYA and PHYB, we found that the N
      terminal half of phyA is also required for Pfr-specific breakdown. Only those
      chimeras containing the N-terminal sequences from phyA were ubiquitinated and
      rapidly degraded as Pfr. Taken together, our data demonstrate that, whereas an
      intact C-terminal domain is essential for phyA degradation, the N-terminal domain
      is responsible for the selective recognition and ubiquitination of Pfr.

PMID- 10074714
TI  - The EMB 506 gene encodes a novel ankyrin repeat containing protein that is
      essential for the normal development of Arabidopsis embryos.
AB  - The EMB 506 gene of Arabidopsis, required for the normal development of the
      embryo beyond the globular stage, has been cloned. The gene encodes a protein of
      predicted size 35 kDa that contains five ankyrin (ANK) repeats within the C
      terminal moiety. ANK repeats are conserved domains of 33 amino acids involved in
      specific recognition of protein partners. The EMB 506 protein was detected at
      different stages of silique development but accumulated preferentially in the
      mature cauline leaves. The rescue of homozygous emb 506 embryos by
      complementation with the wild-type sequence cDNA demonstrated that the emb
      mutation is a consequence of the T-DNA insertion and that integration and
      expression of the transgene occurred during gametogenesis and/or early embryo
      development. In addition to the drastic effect of the emb 506 mutation during
      embryo development, complementation experiments revealed another effect of the
      gene: emb 506 plants transformed with the wild-type EMB 506 sequence were able to
      produce viable seeds but showed a reduction of apical dominance and the presence
      of adventitious buds or bracts along the stem. This result supports the idea that
      genes essential for embryogenesis may also be required at other stages of the
      plant life cycle.

PMID- 10074715
TI  - Direct evidence for anthocyanidin synthase as a 2-oxoglutarate-dependent
      oxygenase: molecular cloning and functional expression of cDNA from a red forma
      of Perilla frutescens.
AB  - Anthocyanidin synthase (ANS), an enzyme of the biosynthetic pathway to
      anthocyanin, has been postulated to catalyze the reaction(s) from the colorless
      leucoanthocyanidins to the colored anthocyanidins. Although cDNAs have been
      isolated that encode putative ANS, which exhibits significant similarities in
      amino acid sequence with members of a family of 2-oxoglutarate-dependent
      oxygenases, no biochemical evidence has been presented which identifies the
      actual reaction that is catalyzed by ANS. Here we show that anthocyanidins are
      formed in vitro through 2-oxoglutarate-dependent oxidation of leucoanthocyanidins
      catalyzed by the recombinant ANS and subsequent acid treatment. A cDNA encoding
      ANS was isolated from red and green formas of Perilla frutescens by differential
      display of mRNA. Recombinant ANS tagged with maltose-binding-protein (MBP) was
      purified, and the formation of anthocyanidins from leucoanthocyanidins was
      detected by the ANS-catalyzed reaction in the presence of ferrous ion, 2
      oxoglutarate and ascorbate, being followed by acidification with HCI. Equimolar
      stoichiometry was confirmed for anthocyanidin formation and liberation of CO2
      from 2-oxoglutarate. The presumptive two-copy gene of ANS was expressed in leaves
      and stems of the red forma of P. frutescens but not in the green forma plant.
      This corresponds to the accumulation pattern of anthocyanin. The mechanism of the
      reaction catalyzed by ANS is discussed in relation to the molecular evolution of
      a family of 2-oxoglutarate-dependent oxygenases.

PMID- 10074716
TI  - A male gametophyte-specific monosaccharide transporter in Arabidopsis.
AB  - The AtSTP2 gene (sugar transport protein 2) of Arabidopsis thaliana encodes a
      high affinity, low specificity monosaccharide carrier that can transport a number
      of hexoses and pentoses at similar rates. AtSTP2 has 12 putative transmembrane
      helices and a molecular mass of 55.0 kDa. AtSTP2 expression was localized in
      AtSTP2 promoter-beta-glucuronidase (GUS) Arabidopsis plants showing AtSTP2-driven
      GUS activity during pollen maturation and also in germinating pollen.
      Immunohistochemical studies with anti-AtSTP2 antiserum as well as RNA in situ
      hybridization analyses modified these results and showed that AtSTP2 expression
      is confined to the early stages of gametophyte development. Both AtSTP2 mRNA and
      AtSTP2 protein are first seen at the time of beginning callose degradation and
      microspore release from the tetrades. AtSTP2 mRNA and AtSTP2 protein are no
      longer detected after the mitotic divisions and the formation of the trinucleate
      gametophyte. No AtSTP2 mRNA or AtSTP2 protein is seen in fully developed or
      germinating pollen. The putative role of AtSTP2 in the uptake of glucose units
      resulting from callose degradation during pollen maturation is discussed.

PMID- 10074717
TI  - Identification of genes expressed during early Arabidopsis carpel development by
      mRNA differential display: characterisation of ATCEL2, a novel endo-1,4-beta-D
      glucanase gene.
AB  - The floral homeotic gene AGAMOUS (AG) imparts carpel identity on the fourth whorl
      of floral organs in wild-type Arabidopsis flowers. Less is known about the genes
      that regulate carpel patterning and differentiation. To identify cndidate
      regulators, we screened for genes expressed in developing carpels. Since
      Arabidopsis carpels are difficult to isolate, we used whole inflorescence apices
      of two floral homeotic mutants (pi and pi ag) and mRNA differential display, to
      identify carpel transcripts. Two of the resulting cDNA clones were shown to be
      expressed predominantly in flowers. They encoded AGL11, a MADS box transcription
      factor known to be expressed in the carpel and ovules, and a novel Arabidopsis
      endo-1,4-beta-D-glucanase (ATCEL2). In situ hybridisation localised the ATCEL2
      transcript to the developing septum and ovule primordia of young carpels.

PMID- 10074718
TI  - Diversity and similarity among recognition sequences of Dof transcription
      factors.
AB  - Dof proteins are a family of transcription factors that share a unique DNA
      binding domain. Dof proteins were found recently in association with diverse
      promoters of plant-specific genes, suggesting various roles of Dof proteins in
      plants. Through binding site selection experiments using randomly synthesized
      DNA, the recognition sequences of four maize Dof proteins were systematically
      analyzed. All selected oligonucleotides contained an AAAG sequence, suggesting
      that this sequence is the recognition core of Dof proteins. In fact, a single
      mutation in this sequence abolished binding of all four Dof proteins.
      Furthermore, the preference of each Dof protein for the sequence flanking the
      core motif was also analyzed using oligonucleotides containing a fixed AAAG and
      random flanking sequences. Similar, as well as distinct, flanking sequences were
      observed among the optimal binding sites. Changes in the flanking sequences did
      affect DNA-binding of Dof proteins.

PMID- 10074719
TI  - Prognostic factors in node-negative breast cancer patients: the experience in
      Taiwan.
AB  - BACKGROUND: Adjuvant chemotherapy has improved the length of disease-free
      survival and overall survival in node-negative breast cancer patients. It has
      been a common practice to select only the patients with higher rates of
      recurrence for adjuvant therapy. Therefore, it is essential to define the risk
      factors in node-negative breast cancer patients. MATERIALS AND METHODS: Two
      hundred fifty-five patients with axillary node-negative breast cancers without
      adjuvant chemotherapy or hormonal therapy at Chang Gung Memorial Hospital between
      1981 and 1986 were included in this study. Tissue blocks for DNA flow cytometry
      study was available in the tumors of 145 patients. RESULTS: The median follow-up
      period was 121 months and the percentages of patients with 10 years of disease
      free survival (DFS) and overall survival (OS) were 75.1% and 82.2%, respectively.
      The significant poor prognostic factors for 10 years of OS were a tumor size
      larger than 3 cm, negative estrogen and progesterone receptor status, and having
      a non-diploid tumor (p value = 0.0176, 0.048 and 0.016, respectively). The
      patients with frozen section, high mitotic rate, and Scarff-Blood-Richardson
      (SBR) grade II and III tumors had a worse prognosis than the others, but this
      trend did not reach statistical significance. The patients with positive estrogen
      receptor status had a 10-year disease-free rate (DFR) of 94%, and these with
      tumors less than 2 cm plus SBR grade I had a 10-year DFR of 92%. CONCLUSION: The
      node-negative breast cancer patients with a low risk of recurrence were those who
      had estrogen receptor positive, tumor less than 2 cm with SBR grade I, and
      intraductal carcinomas. Adjuvant chemotherapy would be no benefit for these
      patients.

PMID- 10074720
TI  - The use of prophylactic intravenous immunoglobulin therapy in very low
      birthweight infants.
AB  - BACKGROUND: Nosocomial infections are a major cause of death in premature
      infants, especially in very low birthweight (VLBW) infants. The VLBW infants have
      low serum immunoglobulin G levels, which may have an effect on infections in
      early infancy. Thus, prophylactic administration of intravenous immunoglobulin
      (IVIG) is proposed to maintain higher immunoglobulin G and reduce the rate of
      hospital-acquired infection. MATERIALS AND METHODS: A study for the effects of
      prophylactic IVIG therapy in VLBW infants was performed. A total of 61 VLBW
      infants were enrolled, and divided into the IVIG group (n = 31) and the control
      group (n = 30). The dose for each infant was 750-1000 mg/kg for those whose
      birthweight was less than 1000 g, and 500-750 mg/kg for infants whose birthweight
      was between 1001 and 1500 g. The control group received saline infusion. The
      infusions were given every 2 weeks until the infant weighed 1800 g, or was
      discharged. RESULTS: The results showed: there were no major differences in the
      perinatal and neonatal characteristics between the two groups, consistently
      higher IgG levels were found in the IVIG group, and the age of first documented
      sepsis was earlier in the control group. CONCLUSION: In this study, the
      prophylactic IVIG therapy may give substantially higher IgG levels, which may
      last for 2 months. However, a prophylactic effect for hospital-acquired
      infections was not observed.

PMID- 10074721
TI  - Papillary and follicular thyroid carcinomas with bone metastases: a series of 39
      cases during a period of 18 years.
AB  - BACKGROUND: Bone metastases can cause death in patients with papillary or
      follicular thyroid carcinoma. There is, however, limited information about the
      clinical presentations and prognoses of patients with papillary and follicular
      thyroid carcinomas with bone metastases in Taiwan. MATERIALS AND METHODS: A
      series of 39 patients with papillary or follicular thyroid carcinomas with bone
      metastases treated at our center from 1977 through 1995 was retrospectively
      reviewed to elucidate the clinical presentations and results of treatment of this
      disease. RESULTS: The occurrence rate of bone metastasis in papillary and
      follicular thyroid carcinomas was 4.3%. Of the 39 patients, whose mean age was
      57.5 years, 28 (71.8%) had follicular and 11 (28.2%) had papillary carcinomas.
      Thirty-two patients (82.1%) were female and 7 (17.9%) were male. Twenty-nine
      patients (74.4%) presented with bone metastases before the thyroid cancers were
      diagnosed. Bone metastases were detected using radiography in 33 patients and
      using 131I scans in 28 patients. Thirty-one patients (79.5%) had multiple bone
      metastases. The spine was the most frequently involved site (53.8%). Three
      patients were disease-free and 14 patients died during the course of treatment.
      Using the Kaplan-Meier method, the 5-year survival rate was estimated to be
      64.9%. CONCLUSION: Bone metastasis, although rare in patients with papillary
      carcinoma, was not very uncommon in patients with follicular carcinoma. Bone
      metastases occurred more often in older patients. Multiple bone metastases were
      noted more often than single bone metastasis. Most patients had symptoms and
      signs resulting from metastatic bone lesions. Although multimodality therapy was
      tried, the prognoses for most patients with bone metastases were poor.

PMID- 10074722
TI  - Survival advantages and complications of adjuvant therapy in early-stage cervical
      cancer with pelvic node metastasis.
AB  - BACKGROUND: Patients with early-stage cervical cancer who have pelvic node
      metastasis usually need adjuvant therapy after surgery for improvement of the
      length of survival. We attempted to determine the survival advantages and
      complications associated with different adjuvant therapeutic modalities.
      MATERIALS AND METHODS: Eighty-seven patients with clinical stage Ib and IIa
      cervical cancer were treated with radical hysterectomy from July 1986 through
      December 1994 were reviewed retrospectively. All had had lymph node metastasis.
      The patients were divided into three groups according to the different adjuvant
      therapeutic approaches utilized: radiation (group I, n = 43), chemotherapy (group
      II, n = 23), and chemoirradiation (group III, n = 21). RESULTS: There was no
      significant difference among these three groups in the 5-year relapse-free
      survival rate (group I: 63%, group II: 62%, group III: 51%, p = 0.785). The
      recurrence rates among these three groups were found to be similar (group I:
      32.6%, group II: 39.1%, group III: 47.6%, p = 0.331). However, most of the
      recurrence in patients who had received pelvic radiation was at a distant site
      (group I: 79%, group III: 80%) as compared to the patients who had received
      chemotherapy only (group II: 33%), and the differences were significant (p =
      0.020). The rates of complications, such as severe leukopenia, lymphedema with
      cellulitis, proctosigmoiditis and ileus, were found to be lower in the
      chemotherapeutic group. CONCLUSION: Although we failed to demonstrate the
      survival advantages of different adjuvant therapeutic approaches, we still favor
      chemotherapy as an adjuvant basis because it is the least toxic of the regimens.

PMID- 10074723
TI  - Premaxillary size and craniofacial growth in patients with cleft lip and palate.
AB  - BACKGROUND: Premaxillary size in individuals with cleft lip and palate is
      variable, ranging from a mere nubbin to a large protuberance. The purpose of this
      study was to evaluate the effect of premaxillary size on craniofacial growth in
      cleft lip and palate patients. MATERIALS AND METHODS: Premaxillary size was
      measured using 181 dental casts of bilateral complete cleft lip and palate (BCLP)
      infants. The infants had no associated systemic malformations, and were
      approximately one year of age. Data were obtained from the files of the Chang
      Gung Craniofacial Center. The mean size (mean = 19.3 mm) of the premaxilla and
      standard deviation (SD = 2.0 mm) were calculated. A sample of 55 subjects was
      divided into three groups: large premaxilla; [LP; 15 boys, 5 girls; mean age 5.2
      years; premaxillary size > (19.3 + 2.0) mm; mean size 22.6 mm]; small premaxilla
      [SP; 15 boys, 5 girls; mean age = 5.1 years; premaxillary size < (19.3-2.0) mm;
      mean size = 16.5 mm] and bilateral-median facial dysplasia [B-MFD; 6 boys, 9
      girls; mean age 5.1 years; mean size 10.5 mm]. They all had a bilateral
      cheiloplasty at about 3 months of age and palatoplasty at about one year of age.
      Lateral cephalograms were taken at about 5 years of age to compare the
      craniofacial complex among the three groups. RESULTS: The LP group tended to have
      a longer maxilla, longer anterior maxillary height and more protruded maxilla,
      producing a better interjaw relation and larger overjet. The opposite phenomena
      were observed in the B-MFD group, and the SP group had results between those of
      the LP group and the B-MFD group. CONCLUSION: BCLP patients with large premaxilla
      had superior maxillary growth (in depth and anterior height) as compared to those
      with small premaxilla.

PMID- 10074724
TI  - Porous coated anatomic total hip arthroplasty: 5- to 10-year follow up.
AB  - BACKGROUND: We report the medium term results of a study of patients with
      noncemented total hip arthroplasty (THA) using a first generation porous coated
      anatomic (PCA) prosthesis. MATERIALS AND METHODS: We reviewed 161 primary
      uncemented PCA THAs performed in 141 patients from November 1985 through March
      1989 in our hospital. Subjects were followed up for a minimum of 5 years or until
      revision. Most common indicators for THA were osteoarthritis in 81 hips (50.3%)
      and avascular necrosis in 64 hips (39.8%). The average age at operation was 48.2
      years. The average follow-up period was 6.9 years in patients without revision.
      RESULTS: The average modified d'Aubigne and Postel hip scores improved from 10.9
      points preoperatively to 17.4 points at the final postoperative evaluation.
      Results were rated as good to excellent in 146 hips (90.7%). Twelve (7.4%) hips
      received revision arthroplasty, 8 because of cup loosening, one because of
      polyethylene wear, and 3 hips because of stem loosening. Prostheses were removed
      in 2 hips, one due to tuberculosis and the other due to infection. Other
      complications included focal osteolysis in 54 hips (33.5%), posterior dislocation
      in 3 hips (1.9%), and lesser trochanter fracture in one hip. Thigh pain occurred
      in 30 hips (18.6%). In 114 hips, the roentgenograms were used to assess
      polyethylene wear. The average wear rate was 0.11 +/- 0.15 mm/year. Excessive
      wear rate (> 0.2 mm/year) occurred in 28 hips (24.6%). Factors contributing to
      higher wear rate included young age, cup inclination angle beyond the range of 35
      55 degrees, and thin polyethylene liner. CONCLUSION: The high rate of osteolysis
      and thigh pain in these patients should alert surgeons to be cautious in using
      this type of prosthesis.

PMID- 10074725
TI  - 133Xenon ventilation scan as a functional assessment in bronchiectasis.
AB  - BACKGROUND: Mucus impaction in the airways impairs ventilation and exercise
      tolerance in patients with bronchiectasis. Parameters for evaluating the
      ventilatory dynamic change have been limited by variable cofactors. We developed
      a tool to evaluate the changes directly on images of a ventilation scan.
      MATERIALS AND METHODS: We used a 133Xenon ventilation washout scan to assess the
      time of half clearance (T1/2) of the regions of interest (ROIs) corrected by that
      of a control area (CA) as T1/2ROI/CA. We then compared the ventilation washout
      scan with high-resolution computer tomography (HRCT) scoring to assess the
      severity of bronchiectasis, as well as conducting 6-minute walking tests or
      spirometry for the evaluation of the clinical response to a 3-day course of chest
      physiotherapy. Nine patients with bronchiectasis and mucus hypersecretion were
      enrolled in this study. RESULTS: The functional impairments by mucus impaction or
      air trapping were well documented in the ventilation washout scan, which not only
      provided an anatomical image but also dynamic profiles. The ratios of T1/2ROI/CA
      were significantly correlated to the corresponding scoring of HRCT (3.45 +/- 0.85
      vs 7.50 +/- 1.51, r2 = 0.61, p = 0.023, n = 8). The improvement in T1/2ROI/CA
      (from 3.45 +/- 0.85 to 2.60 +/- 0.59, p = 0.022, n = 9) was paralleled by an
      increase in the 6-minute walking test (from 310.4 +/- 43.2 m to 352.4 +/- 45.1 m,
      p = 0.028, n = 7). CONCLUSION: The 133Xenon scan may be used to evaluate the
      heterogeneity of ventilation abnormalities and the efficacy of clinical therapy
      directly in patients with bronchiectasis.

PMID- 10074726
TI  - Chest physiotherapy does not exacerbate gastroesophageal reflux in patients with
      chronic bronchitis and bronchiectasis.
AB  - BACKGROUND: Chest physiotherapy is beneficial to patients with mucus
      hypersecretion. However, it is not risk-free. Chest physiotherapy may affect
      gastrointestinal motility and the competence of the gastroesophageal sphincter
      during the procedure. Our study was aimed to investigate whether gastroesophageal
      reflux is exacerbated or induced by chest physiotherapy. MATERIALS AND METHODS:
      Thirty-two adult patients with chronic bronchitis or bronchiectasis received
      chest physiotherapy. An esophageal pH meter was placed 5 cm above the
      gastroesophageal junction and monitored the reflux episodes from 8 AM on the
      first day to 12 noon on the second day. Physiotherapy was performed with the
      patient in three different positions on the second day for one hour. RESULTS:
      Thirteen patients were found to have gastroesophageal reflux disease. For the
      study group as a whole, neither the frequency nor the duration of having a pH < 4
      during the physiotherapy was significantly different from the mean hourly
      frequency and mean hourly duration recorded on the first day or from those values
      recorded at a corresponding time on the first day. As for the patients with
      gastroesophageal reflux disease, the frequency and total duration of
      gastroesophageal reflux during physiotherapy were not significantly different
      from the mean hourly frequency and the mean hourly duration or from the values
      recorded at the corresponding time on the first day. There was no significant
      difference in the gastroesophageal reflux frequency or the duration in different
      body positions. CONCLUSION: Chest physiotherapy including postural drainage,
      percussion and forced expiration techniques in different positions did not induce
      or increase the incidence of gastroesophageal reflux in patients with chronic
      bronchitis and bronchiectasis.

PMID- 10074727
TI  - Squamous cell carcinoma of the bladder: a ten-year retrospective study.
AB  - BACKGROUND: There is a limited amount of information available on treatment
      efficacy and optimal management of squamous cell carcinoma of bladder. The goal
      of this study was to assess the long-term outcome of patients with squamous cell
      carcinoma of the bladder treated using different modalities. MATERIALS AND
      METHODS: Retrospective analysis of the medical records of 22 patients with
      squamous cell carcinoma of the bladder treated at Chang Gung Memorial Hospital
      from 1986 though 1996 was performed. The follow-up period ranged from 12 months
      to 111 months. RESULTS: The treatment modalities included transurethral resection
      in 7 patients, radical cystectomy with urinary diversion in 6 patients,
      preoperative radiation followed by total cystectomy in 8 patients, and partial
      cystectomy in one patient. The overall 5-year survival rate was 9%. Only 6
      patients (27.3%) in this series were alive two years after diagnosis. Treatment
      using a combination of modalities including preoperative radiation followed by
      total cystectomy resulted in a 5-year survival rate of 12.5% in 8 patients. Total
      cystectomy alone in 6 patients resulted in a 5-year survival rate of 0%. However,
      the difference in survival rates between these 2 treatment groups was not
      statistically significant. CONCLUSION: Our results suggest that no definite
      significance concerning the role of preoperative radiation followed by total
      cystectomy could be drawn. The results were probably because most of our patients
      had locally advanced bladder cancer. Another consideration is the small sample
      size, which may have affected the significance. Although, cystectomy did not
      improve the 5-year survival rate of patients in this series, it improved the 2
      year survival rate.

PMID- 10074728
TI  - Curve patterns and etiologies of scoliosis: analysis in a university hospital
      clinic in Taiwan.
AB  - BACKGROUND: The curvature characteristics and etiologies of scoliosis have been
      well documented in many countries and among different races but have seldom been
      reported for Asians. We aimed to determine the etiology frequency and curvature
      characteristics of scoliotics in Taiwan. MATERIALS AND METHODS: From July 1994
      through December 1997, 648 new patients with scoliosis were examined. A whole
      spine standing radiographic study was taken for each patient. The data were
      collected prospectively for analysis. RESULTS: Idiopathic scoliosis was the
      leading type in our series (86%), followed by congenital (6%) and neuromuscular
      scoliosis (5%). Single thoracic curve was the most common curve pattern (37%),
      followed by single lumbar (30%), double major (13%), single thoracolumbar (13%),
      and double thoracic curve (6.6%). The most frequent types of curve were right
      thoracic (28%) and left lumbar curve (22%), and these were defined as typical
      curves. The average curve magnitude was smaller in patients with atypical curves
      (left thoracic or right lumbar) and large curves were not commonly seen. The
      average curve magnitude increased in patients from the ages of 8 to 12 years and
      it exceeded Cobb's angle of 20 degrees at the age of 11. CONCLUSION: Idiopathic
      scoliosis is the most frequent etiology of scoliosis in Taiwan. In our series,
      idiopathic scoliosis was female predominant (4.3:1), but there were no gender
      ratio differences in non-idiopathic patients (p < 0.001). Left thoracic curve
      occurred more often in juvenile idiopathic scoliotics (p = 0.006). Atypical
      curves were more resistant to curve progression and seldom induced large curves.
      School scoliosis screening beginning at age 11 is adequate and effective in
      Taiwan.

PMID- 10074729
TI  - Tandem spinal stenosis: clinical diagnosis and surgical treatment.
AB  - BACKGROUND: Tandem spinal stenosis (TSS) is defined as spinal stenosis that
      combines cervical and lumbar spinal stenosis. The primary manifestations include
      intermittent neurological claudication, progressive gait disturbance, and mixed
      symptoms and signs of the upper and lower extremities. MATERIALS AND METHODS:
      From April 1994 through September 1995 in a series of 158 patients who underwent
      surgery for spinal stenotic syndrome, 12 patients were diagnosed with TSS, with
      an overall incidence of 7.6%. Our management guidelines required that cervical
      surgery be performed first if the patients had signs in the upper motor neuron
      region or predominant signs in the upper extremities. In the patients who had
      significant symptoms in the lower extremities and no signs in the upper motor
      neuron region, lumbar surgery was performed first. RESULTS: In this series, 8 of
      12 patients received cervical surgery first and 4 required further lumbar
      surgery. Among the 8 patients who received cervical surgery, 2 received
      Hirabayashi's laminoplasty, 3 laminectomy, and 3 anterior decompression and
      fusions. The other 4 patients received lumbar surgery only. The average follow-up
      period was 32 months (range, 24-40 months). At the latest examinations, 8
      patients (66.7%) had excellent or good clinical results. CONCLUSION: Our results
      revealed that when correct diagnosis and management for patients with TSS was
      given, the patients usually had satisfactory outcomes. Ossification of the
      posterior longitudinal ligament (OPLL) was noted in 7 of 12 patients (58.3%) in
      this study. Thus, OPLL might be a predominant factor in TSS, and larger
      populations studies are needed to confirm this finding.

PMID- 10074730
TI  - Spinal fusion and pedicle screw instrumentation in the treatment of
      spondylolisthesis over the age of 60.
AB  - BACKGROUND: Spinal fusion or instrumentation for the treatment of
      spondylolisthesis in elderly people is still an issue of controversy. The purpose
      of this study was to assess the clinical results of laminectomy, posterolateral
      fusion, and pedicle screw instrumentation in patients over age 60. MATERIALS AND
      METHODS: From 1993 through 1994, 94 spondylolisthesis patients over age 60
      underwent laminectomy, posterolateral fusion and pedicle screw instrumentation.
      All the patients had follow-up examinations 3 months, 6 months, 1 year and then
      annually after the operation. At each follow-up visit, the clinical results and
      complications were evaluated and a radiographic assessment was performed. The
      follow-up period ranged from 2 to 4 years. At the final follow-up visit, we
      administered a questionnaire designed for clinical evaluation. RESULTS: Seventy
      five patients (80%) obtained improvement in back pain, 75 patients (80%) got
      improvement in leg pain, and 65 patients (69%) needed no medications. The average
      distance the patients were able to walk, at one time was 2.2 km. Sixty-seven
      patients (71%) could walk more than 500 m at a time. Seventy-four patients (79%)
      showed solid fusion, 20 patients inadequate fusion, and no psuedoarthrosis was
      found. Complications were rare. CONCLUSION: Laminectomy with spinal fusion and
      instrumentation is a good method for the treatment of spondylolisthesis in
      elderly people, and it can achieve a satisfactory clinical outcome.

PMID- 10074731
TI  - Hypertrophic peroneal tubercle with stenosing tenosynovitis: the results of
      surgical treatment.
AB  - BACKGROUND: A hypertrophic peroneal tubercle creates a stenotic tunnel which
      triggers a painful peroneal longus. The painful condition is rare, so delayed
      diagnosis frequently occurs. The purpose of this study was to retrospectively
      analyze the diagnosis and the functional results of this condition. MATERIALS AND
      METHODS: A consecutive series of 6 patients with painful hypertrophy of the
      peroneal tubercle was surgically treated with simple resection of the peroneal
      tubercle and tenosynovectomy. There were 4 women and 2 men with a median age of
      26 years. The clinical symptoms included a prominence at the lateral calcaneus
      with tenderness. The symptoms were exaggerated with ankle motion. X-ray and
      computed tomography scanning revealed a bony prominence at the lateral calcaneal
      cortex. RESULTS: An enlarged peroneal tubercle and stenosing tenosynovitis were
      found in all patients. The associated findings included a ganglion cyst in one
      patient, entrapment of a branch of the sural nerve in one patient, and skin
      callatosis with bursitis in one patient. After a median follow-up period of 35
      months, all patients had achieved satisfactory functional results, which included
      freedom from pain, good peroneal muscle power, good range of motion of the foot,
      and no limitation in footwear. CONCLUSION: In summary, the clinical symptoms
      caused by a hypertrophic peroneal tubercle rarely occurred. However, the
      diagnosis could be made with careful clinical and radiographic examinations. The
      symptoms were successfully treated by the complete resection of the tubercle,
      tenosynovectomy, and early range of motion exercise of the hindfoot joints.

PMID- 10074732
TI  - The significance of syphilis serology tests on long-term hemodialysis patients.
AB  - BACKGROUND: Syphilis is a sexually transmitted disease. Blood transfusion and
      blood contact are also routes of infection. Patients on long-term hemodialysis
      are at risk during their therapy. The aim of this study is to investigate the
      incidence of syphilis in hemodialysis patients, possible nosocomial infection and
      methods of treatment. MATERIALS AND METHODS: A total of 556 uremic patients on
      maintenance hemodialysis at our hospital on June 1996 were enrolled in the study.
      They all received syphilis screening tests. The rapid plasma reagin (RPR) test
      was used as the primary screening tests and Treponema pallidum hemagglutination
      assay (TPHA) test as the confirmation test. According to the test results,
      patients were classified into false and true-positive groups. The titer of both
      tests were recorded. The patients in the true-positive group were further divided
      into the untreated and treated group depending on whether they had already
      received treatment. The serial change of RPR test titer of the treated group was
      reviewed. RESULTS: Thirty-one patients (5.6%) had positive RPR test results and
      10 patients (1.8%) had false-positive results. The titers of both RPR and TPHA
      tests were rather low in the positive groups. Most of the confirmed syphilis
      patients were asymptomatic and diagnosed serologically. In the treated group, the
      RPR test titer did not show significant decline and no seroconversion was noted
      after treatment. CONCLUSION: We observed that infectious syphilis patients exist
      in our hemodialysis unit and survey for this disease is necessary. The titers of
      both positive RPR and TPHA tests are low. Most diagnosed patients had latent
      syphilis, and serologic response to treatment is probably the same as in general
      population.

PMID- 10074733
TI  - Thoracic disc herniation treated by video-assisted thoracoscopic surgery: case
      report.
AB  - Clinically, thoracic disc herniation occurs much less frequently than herniation
      in the cervical or lumbar regions, and accounts for only 0.15 to 1.8% of all
      intervertebral discs treated surgically. Classically, open thoracotomy is the
      standard procedure for thoracic disc herniation, but this type of surgery can
      cause prolonged postoperative wound pain that jeopardizes the mechanism of
      respiration and postoperative rehabilitation. We report the case of a 41-year-old
      woman with a symptomatic T11-T12 thoracic disc herniation and cord compression.
      Video-assisted thoracoscopic surgery (VATS) was performed to remove the herniated
      disc successfully. Intraoperatively, there was no injury to vital organs or the
      spinal cord. The total operating time was 3.5 hours, and the estimated blood loss
      was 400 ml. Postoperatively, the incisional pain was minimal, and no intercostal
      neuralgia was noted. At her 2-year follow-up examination, she was fully
      ambulatory and free of pain. This type of minimally invasive procedure is a good
      alternative to the classic thoracotomy and proved to be a safe and effective
      procedure for this patient.

PMID- 10074734
TI  - Watermelon stomach--an unusual cause of recurrent upper gastrointestinal bleeding
      in a uremic patient receiving estrogen-progesterone therapy: case report.
AB  - A 50-year-old woman who had been on maintenance hemodialysis for 5 years
      developed severe anemia resistant to treatment with iron supplements and
      erythropoietin 4 months prior to hospital admission. Her stool occult blood test
      was positive, and an initial panendoscopy revealed evidence of possible antral
      gastritis. However, repeated administration of sucralfate, H2 blockers and a
      proton pump inhibitor was not effective in preventing further gastrointestinal
      tract blood loss and subsequent refractory anemia. She required multiple blood
      transfusions and hospital admissions during this period. There was no obvious
      coagulopathy or thrombocytopenia. After her third admission, a second
      panendoscopy demonstrated the typical picture of watermelon stomach. A trial of
      hormone therapy with estrogen and progesterone increased the hemoglobin level
      within a month without further evidence of active gastrointestinal bleeding. From
      our experience with this case, we found that the diagnosis of antral vascular
      ectasia (watermelon stomach) with bleeding requires a high degree of clinical
      alertness and careful endoscopic examination. Estrogen and progesterone therapy
      may provide a good option for treating the disease in uremic patients without an
      obvious complication. To the best of our knowledge, this is the first report
      demonstrating the use of maintenance hormone therapy in a female uremic patient
      to successfully treat watermelon gastric bleeding.

PMID- 10074735
TI  - Fusion of the lumbar spine with a free vascularized fibular bone graft: case
      report.
AB  - Spinal fusion with either non-vascularized or vascularized bone grafts has been
      well documented for inflammatory, degenerative, post-oncological and post
      traumatic reconstruction Vascularized bone graft has been proven to have more
      rapid healing and better clinical results. A few reports have indicated that free
      vascularized fibular bone grafts have been used for reconstruction of the
      cervical and thoracic spine with good clinical results. We report a case of a
      third lumbar vertebra burst fracture successfully treated with a free
      vascularized fibula graft after failure of an initial conventional bone graft.
      The neurological symptoms improved significantly. The strong and straight bone
      quality makes the vascularized fibula an ideal choice for reconstruction of the
      spine. Vascularized fibula bone graft is an option in cases with failed
      nonvascularized bone grafts, in cases where an iliac bone is not suitable for
      reconstruction, or in cases where a poor recipient bed makes having well
      vascularized bone necessary. This report describes our surgical approach and
      demonstrates the versatility of the free fibular osteoseptocutaneous flap for
      reconstruction of any portion of the spine.

PMID- 10074736
TI  - Primary hepatic angiosarcoma: report of a case involving environmental arsenic
      exposure.
AB  - Hepatic angiosarcoma is a rare malignant tumor with a rapidly fatal course. It
      has become a subject of interest because of its intimate relationship with
      environmental carcinogens, such as thorium dioxide (Thorotrast), vinyl chloride
      monomer, and arsenic. We describe a case of a chronic hepatitis B surface antigen
      carrier, with a 20-year history of environmental exposure to arsenical-containing
      agricultural herbicides and bactericides, who developed a hepatic angiosarcoma.
      He died due to rupture of the hepatic angiosarcoma with acute hemoperitoneum 9
      weeks after initial diagnosis. This is a rare case of primary hepatic sarcoma,
      especially in Taiwan where hepatocellular carcinoma is endemic. This case not
      only serves to give more evidence of the relationship between hepatic
      angiosarcoma and arsenical exposure, but also demonstrates the key point in the
      differential diagnosis of liver tumors. Increased familiarity with this disease
      will facilitate correct diagnosis and help to improve management of the condition
      in the future.

PMID- 10074737
TI  - Unusual dental injuries following facial fractures: report of three cases.
AB  - We report 3 cases of unusual dental injuries following facial fractures. The
      first patient sustained intrusion of a maxillary incisor into the nasal cavity
      following a mandibular fracture. The tooth dislocated into the pharynx and was
      found lodged in the piriform fossa during surgery. The second patient sustained
      intrusion of molars into the maxillary sinus following maxillary and mandibular
      fractures. His treatment was delayed due to life-threatening hemorrhage. The
      third case involved ingestion of multiple avulsed teeth into the alimentary tract
      following severe maxillofacial fractures. Although the diagnosis was made more
      than a week after the injury, the patient did not suffer any complications as a
      result of the dental avulsion. The aim of this report is to emphasize the
      possibility of associated dental injuries in patients with facial fractures. The
      trauma surgeon should be cognizant of the importance of carrying out a thorough
      intraoral examination during the initial evaluation. Any missing tooth should be
      considered as possibly displaced into other tissue compartments, and must be
      routinely searched for with x-rays of the skull, cervical spine, chest, and
      abdomen. If full intrusion injury is suspected, further diagnostic investigation
      with facial computed tomography scanning may be worth while.

PMID- 10074738
TI  - Tuberculosis of the ankle: report of four cases.
AB  - Tuberculosis of the ankle joint is relatively uncommon, and the treatment usually
      includes chemotherapy, immobilization and non-weight bearing protection. It is
      easily confused with pyogenic arthritis, which often leads to delayed diagnosis.
      We reviewed the records of 4 patients with ankle tuberculosis with advanced
      articular lesions without evidence of pulmonary tuberculosis. They took
      antituberculous agents for 5 to 6 months. Two of them had positive bacterial
      cultures, and all four had initially received surgical management under the
      impression of pyogenic osteomyelitis. Two patients underwent arthrodesis and the
      other two synovectomy with debridement. The clinical and radiologic results were
      better in the patients who underwent arthrodesis. We consider surgery with open
      biopsy of a painful swelling ankle to be helpful in the differential diagnosis of
      tuberculous and pyogenic arthritis. Arthrodesis in patients with severe
      osteoarticular destruction of the ankle provides a better prognosis and more
      stable joint than other treatment methods.

PMID- 10074739
TI  - Kadish stage C olfactory neuroblastoma successfully treated by chemoradiotherapy:
      report of two cases.
AB  - Olfactory neuroblastoma is an uncommon tumor. It is usually diagnosed at advanced
      stages. Most of the patients have an indolent clinical course with slow
      progression, late recurrence and relative infrequency of distant metastasis.
      Because of the rarity and lack of a randomized clinical trial of patients with
      olfactory neuroblastoma, there is no standard treatment for the disease. The
      survival period has increased as treatments have been improved since 1980.
      Conventional treatments mainly consist of surgery and/or radiotherapy.
      Chemotherapy was only administered to a few patients; however, it achieved good
      response. More clinical experience is needed to improve the treatment strategy in
      order to reduce the possibility of disease recurrence, and also for rescue
      therapy. We present 2 patients with Kadish C tumors treated using chemotherapy
      followed by radiotherapy. Both patients demonstrated rapid and excellent response
      to induction chemotherapy, and have been free of disease for more than 5 years
      and 2 years after treatment, respectively.

PMID- 10074740
TI  - Acute retinal necrosis--early manifestation and successful treatment with steroid
      and acyclovir: case report.
AB  - A healthy 19-year-old woman suffering from pain, redness, and blurred vision of
      her left eye came to our emergency unit for help. Initial examination revealed no
      light-perception, tenderness and marked inflammation of the left eye. There was
      severe inflammation both in the anterior chamber and vitreous cavity. Total
      retinal detachment accompanied by diffuse thickening of choroid was demonstrated
      using echography. Under the impression of panuveitis, oral steroids were given.
      The response of the left eye was dramatic but the patient complained of blurred
      vision of her right eye 2 days after steroid therapy. There was only mild
      reaction in the right eye; however, multiple granule-appearing white dots were
      found on the inferior two-thirds of the peripheral retina. The nummular white
      lesions increased in size and number and finally became confluent in the
      following days. The diagnosis was shifted to acute retinal necrosis and
      intravenous acyclovir was started while continuing systemic steroid therapy. The
      retinal necrosis began to consolidate four days after the administration of
      acyclovir and gradually regressed. We tapered the systemic steroids when the
      intra-venous acyclovir was shifted to oral form. The vitreous of the right eye
      remained clear during the follow-up period. The antiviral agent still suppressed
      the disease process even though steroids had been used beforehand. Furthermore,
      the systemic steroids seemed to ameliorate the vitritis and secondary
      complications in the right eye compared with the fulminant, disastrous course of
      the left eye.

PMID- 10074741
TI  - Primary pericardial mesothelioma with cardiac tamponade and distant metastasis:
      case report.
AB  - Although cardiac tamponade is a well-known complication of malignancy, it is
      uncommon as the initial manifestation. The antemortem diagnosis is difficult and
      distant metastasis is extremely rare. The presentations of primary pericardial
      mesothelioma are nonspecific. Pathologically, mesothelioma is the most common in
      primary tumors of the pericardium. Radical surgery can be used to treat a
      localized mesothelioma. However, the therapy for advanced primary pericardial
      mesothelioma is usually palliative because it is resistant to irradiation, and
      chemotherapy does not markedly improve the outcome. The prognosis is uniformly
      poor. The median survival from the onset of symptoms is 6 months. We present a 67
      year-old woman with cardiac tamponade 4 months prior to a definitive diagnosis of
      primary pericardial mesothelioma. A computed tomogram confirmed multiple well
      enhanced nodules in the pericardium, lungs and liver. Unfortunately, the patient
      died of multiple organ failure.

PMID- 10074742
TI  - Successful removal of a hemangioblastoma from the medulla oblongata: case report.
AB  - Hemangioblastomas are histologically benign tumors that occur exclusively within
      the neuraxis, most commonly in the posterior fossa. They are typically cystic
      tumors located in the cerebellum. Excision of the vascular mural nodules leads to
      cure. Brain stem lesions are rarely reported. Surgical extirpation of a solid
      brain stem hemangioblastoma is relatively risky and requires precise
      microsurgical techniques. We present a woman with a hemangioblastoma embedded in
      the medulla oblongata. This 33-year-old woman presented with occipital headaches
      and sensory ataxia. Complete and detailed preoperative imaging studies were
      followed by successful microsurgical excision of the lesion. The patient
      recovered completely within 2 weeks after the operation except for mild
      paresthesia of the legs. Preoperative magnetic resonance imaging and cerebral
      angiography provided important information regarding the nature, location, and
      blood supply of this lesion, which facilitated its total removal. The importance
      of intraoperative identification and control of the feeding artery of the tumor
      is emphasized.

PMID- 10074743
TI  - Gouty os trigonum tarsi: case report.
AB  - Os trigonum tarsi is found in 7% of the world adult population. However, it
      rarely causes symptoms. The majority of patients with os trigonum tarsi are found
      incidentally. This condition is often found in ballet dancers, javelin throwers
      and soccer players. It rarely produces symptoms in normally active adults. The
      etiology of os trigonum syndrome is impingement of an unfused ossicle or a
      fractured posterior lateral tubercle of talus over the posterior rim of tibial
      plafond. We present a case of os trigonum syndrome in a young man. His posterior
      heel pain was due to tophaceous gout around the os trigonum tarsi, instead of the
      common pathogenesis of repeated hyperflexion of the ankle joint. Pictures of the
      specimen showed marked giant cell reaction which resulted in pseudotumor
      formation. We reviewed the clinical characteristics of os trigonum tarsi and gout
      and present the treatment of our patient.

PMID- 10074744
TI  - Psychogenic vomiting: report of two cases.
AB  - Two patients were admitted to our hospital with the diagnosis of psychogenic
      vomiting of more than 9 months' duration. Both were treated with a combination of
      pharmacotherapy, relaxation training, cognitive therapy and supportive
      psychotherapy. Behavioral therapy and verbal catharsis were also used in one of
      the cases involving bereavement. The intervention was not directly aimed at the
      vomiting, but at the aspects of the patients' stress and emotional problems.
      Change in condition was assessed on basis of the frequency of vomiting and the
      severity of anxiety and depression. Vomiting was found to be positively related
      to anxiety but not to depression. These 2 patients improved to the extent that
      the disturbance caused by vomiting was significantly reduced, and the reduction
      was closely related to the severity of anxiety. Both were also found to have
      similar personality traits and family types, which have been reported to be
      related to psychogenic vomiting. We review the characteristics of psychogenic
      vomiting and relate some important considerations for treating Chinese
      psychogenic vomiting cases.

PMID- 10074745
TI  - Calcified chronic subdural hematoma: case report.
AB  - Calcified or ossified chronic subdural hematoma is a rare entity that usually
      presents as a space-occupying lesion over the cerebral convexity. We report a
      case of calcified and ossified chronic subdural hematoma in an unusual location
      that has not been previously reported. A 24-year-old man with a history of tonic
      clonic convulsions since 7 months of age was admitted because of increasing
      frequency and duration of seizures. Computed tomography and magnetic resonance
      imaging demonstrated a fusiform extra-axial lesion just above the tentorium and
      adjacent to the cerebral falx. A calcified and ossified chronic subdural hematoma
      was noted and was almost completely removed by craniotomy. Better seizure control
      was achieved by removal of the calcified chronic subdural hematoma. Calcified
      subdural hematoma, calcified epidural hematoma, calcified empyema, meningioma,
      calcified arachnoid cyst, and calcified convexity of the dura mater with acute
      epidural hematoma should be considered for the differential diagnosis of an extra
      axial calcified lesion.

PMID- 10074746
TI  - Osmotic demyelination syndrome with two-phase movement disorders: case report.
AB  - Osmotic demyelination syndrome (ODS) is characterized by regions of demyelination
      throughout the brain, which are most prominent in the pons. This demyelinating
      disease is associated with electrolyte disturbances and typically occurs in
      patients who are alcoholic or malnourished. Movement disorders are not frequently
      recognized in patients with ODS. This report describes a 22-year-old woman with
      ODS after correction of profound hyponatremia. The main neurologic symptom was
      two-phase movement disorder. First, she had acute onset dystonia, then the
      movement disorder transformed to generalized rigidity and tremors in the delayed
      second phase. Magnetic resonance imaging in the first phase revealed
      demyelinating lesions in the central pons, bilateral thalami and basal ganglia.
      In the second phase, the previous myelinolysis had been partially resolved. The
      clinical course of the two-phase movement disorder did not correlate with the
      resolving feature of neuroradiologic findings. During the second-phase movement
      disorder, the patient had a good response to propranolol and trihexyphenidyl.

PMID- 10074747
TI  - The century of osseointegration.

PMID- 10074748
TI  - Ancient "dental implants": a recently proposed example from France evaluated with
      other spurious examples.
AB  - The recent announcement of the discovery of a first or second century AD Roman
      example of a dental implant appears to fall into a category of spurious claims
      regarding ancient dentistry. Several earlier claims of the discovery of
      impressive examples of ancient dentistry are reviewed, followed by a discussion
      of the recent discovery from France. This survey of all of these claims regarding
      finds of ancient dental implants, plus data from the modern and rapidly evolving
      field of implant dentistry, suggests that these "ancient implants" are the
      product of the imaginations of 20th-century archaeologists.

PMID- 10074749
TI  - Palatal sliding strip flap: soft tissue management to restore maxillary anterior
      esthetics at stage 2 surgery: a clinical report.
AB  - A new soft tissue flap design technique, called "the palatal sliding strip flap"
      (PSSF), has been developed to improve the soft tissue surgical results at stage 2
      implant surgery. The purpose of this flap design is to help form papillae between
      implants and between natural teeth in the anterior area of the maxilla. The flap
      is designed and managed so that the palatal attached mucosa slides in a labial
      direction to create papillae and at the same time augment the labial ridge. This
      surgical approach is valid, predictable, and has a low risk-to-benefit ratio.
      This new flap design is indicated for a variety of clinical situations,
      especially for the problematic maxillary soft tissue reconstruction around teeth
      and implants.

PMID- 10074750
TI  - Formation of mineralizing osteoblast cultures on machined, titanium oxide grit
      blasted, and plasma-sprayed titanium surfaces.
AB  - Altering osseous responses at implant surfaces to enhance bone is a current goal
      of clinical therapy. Cell culture may be used to investigate surface-dependent
      responses of bone-forming cells. In this report, the ability of primary fetal
      bovine mandibular osteoblast cultures to form a mineralizing matrix on machined,
      titanium plasma-sprayed, and titanium oxide grit-blasted surfaces has been
      compared. Immunohistochemical markers associated with bone formation were used to
      define the differentiated state of the formed matrix using qualitative light
      microscopy, and von Kossa staining was used to demonstrate the presence of
      mineralization within this matrix. Compared to either titanium oxide grit-blasted
      or machined surfaces, titanium plasma-sprayed surfaces displayed a unique pattern
      of mineralized matrix formation. Scanning electron microscopy further revealed
      that each surface accumulated unique organic and inorganic deposits during matrix
      formation, suggesting that surface-dependent physicochemical and biochemical
      conditioning of implant surfaces takes place. Surface topographic features of
      commercially pure titanium substrates can alter cultured osteoblast extracellular
      matrix formation and mineralization. Similar molecular and cellular assessment of
      in vivo responses to implant surface topography may contribute to improved
      engineering of endosseous implants.

PMID- 10074751
TI  - Surgical implant repositioning: a clinical report.
AB  - Esthetically compromised or nonrestorable implants present major clinical
      problems. Of 3,850 implants placed, 10 osseointegrated implants in 6 patients
      were surgically repositioned using maxillary or mandibular osteotomies and
      rigidly fixated, under intravenous sedation. The segments were predictably
      changed in a vertical, anteroposterior, transverse, or axial inclination manner.
      Excellent healing of bone and soft tissue was observed. This simple, reliable
      technique allowed these 10 implants to be esthetically and functionally restored
      with permanent prostheses.

PMID- 10074752
TI  - Sinus augmentation for single-tooth replacement in the posterior maxilla: a 3
      year follow-up clinical report.
AB  - A technique for single-tooth sinus lift and simultaneous implant placement in the
      posterior maxilla is presented. Ten hydroxyapatite-coated cylindric implants, 13
      to 15 mm in length, were placed together with a composite bone graft of
      demineralized freeze-dried bone allograft and autogenous bone in 10 adults.
      Surgical technique and anatomic considerations are discussed. Follow-up of 3
      years showed successful function and no cervical bone loss in all patients.

PMID- 10074753
TI  - Histomorphometric evaluation of the effect of hyperbaric oxygen treatment on
      healing around hydroxyapatite implants in irradiated rat bone.
AB  - The effect of hyperbaric oxygen (HBO) on the tissue reaction around
      hydroxyapatite (HA) implants in irradiated bone of rats was investigated. A
      single dose of 15 Gy was delivered to the right leg of 20 rats. HA implants were
      placed in the bilateral tibial proximal metaphysis 3 months after irradiation.
      HBO was administered to half of the rats before and after 15-Gy irradiation. The
      healing process was examined histologically and histomorphometrically. The
      results indicated that HBO slightly improved trabecular bone formation in the
      irradiated bone, accelerated bone remodeling in the nonirradiated bone, and
      improved HA-bone contact in both the irradiated and nonirradiated bones.

PMID- 10074754
TI  - Laser-welded titanium frameworks for implant-supported fixed prostheses: a 5-year
      report.
AB  - The 5-year results from a multicenter study of implant-supported, laser-welded
      titanium frameworks are reported here as a complement to earlier reported 2-year
      results. Implant survival rates were satisfactory for patients with titanium
      frameworks and for a control group of patients with gold-alloy frameworks. At the
      5-year review, more patients with titanium frameworks had lost implants than the
      patients with gold-alloy frameworks, but this difference was not statistically
      significant. More fractures of the titanium frameworks occurred, compared to the
      gold-alloy frameworks; again, this difference was not statistically significant.
      No significant differences in marginal bone levels were found between the 2
      groups of patients. Slightly more fractures of artificial teeth occurred in
      patients with titanium frameworks than in patients with gold-alloy frameworks.
      Overall results for the titanium frameworks after 5 years in function are
      encouraging.

PMID- 10074755
TI  - A comparative study of anorganic xenogenic bone and autogenous bone implants for
      bone regeneration in rabbits.
AB  - The aim of this study was to investigate the possible use and ultimate fate of
      anorganic xenogenic bone for the restoration of defects in the maxillae and
      mandibles of adult rabbits. Furthermore, anorganic xenogenic bone was compared
      with implanted autogenous bone particles with regard to the response of the
      surrounding connective tissue and possible resorption of these implants by
      multinucleated cells. Results showed that after 12 weeks, the implanted
      autogenous bone was actively resorbed by multinucleated cells, and new bone was
      formed in close apposition to the particles. In contrast, implanted anorganic
      xenogenic bone was degraded to a much lesser extent, and new bone was seen
      adjacent to the anorganic bone particles without signs of resorption. Further
      long-term studies are needed to determine whether anorganic xenogenic bone may be
      regarded as a resorbable material and whether any side effects occur as a result
      of this material's tendency to linger on in the recipient bed.

PMID- 10074756
TI  - Tube angulation effect on radiographic analysis of the implant-abutment
      interface.
AB  - The purpose of this study was to determine the maximum permissible x-ray tube
      angulation that can be used to verify the fit of an abutment. An implant and an
      abutment were assembled with an abutment screw. A variety of openings were
      created between the abutment and the implant. Radiographs were taken combining
      the different gaps with various x-ray tube angulations. The radiographs were
      randomly presented to 8 clinicians, who judged the interface as open or closed.
      The results indicate that a radiographic analysis of interface openings becomes
      subjective with tube angulations of more than 5 degrees.

PMID- 10074757
TI  - Placement of endosseous implants into bone-grafted alveolar clefts: assessment of
      bone bridge after autogenous particulate cancellous bone and marrow graft.
AB  - The objective of this study was to evaluate the bone quantity of alveoli grafted
      with autogenous particulate cancellous bone and marrow for implant placement in
      patients with alveolar clefts. Bone height, bone width, and interdental alveolar
      crest level were evaluated using computed tomography and periapical radiographs.
      The grafted alveoli underwent resorption 3-dimensionally, and the interdental
      alveolar crest level also decreased. The latter seemed to be the critical factor
      for implant surgery, as almost half of the grafted alveoli required another bone
      graft within 24 months after the original bone graft to increase the interdental
      alveolar crest level for endosseous implant placement. These data suggest that
      alveoli grafted with particulate cancellous bone and marrow are suitable for
      implant placement, but that the loss of width and height of the bone bridge must
      also be considered.

PMID- 10074758
TI  - Microleakage at the abutment-implant interface of osseointegrated implants: a
      comparative study.
AB  - Microleakage can occur at the abutment-implant (A-I) interface in osseointegrated
      implants and may cause malodor and inflammation of peri-implant tissues. The
      degree of microleakage at the A-I interface of 5 implant systems was
      comparatively assessed at varying closing torques. Using colored tracing probes
      driven by a 2-atm pressure system, the interface microleakage of Branemark,
      Sulzer Calcitek, 3i, ITI, and Steri-Oss implants was determined
      spectrophotometrically. Microleakage through the A-I interface occurred in all
      systems, with variability between systems, samples, and closing torques. As
      closing torque increased from 10 Ncm to 20 Ncm to manufacturers' recommended
      closing torques, microleakage decreased significantly (P < .005) for all systems.
      Analysis of variance showed significant interaction between closing torques and
      the time course of microleakage, and between systems and the time course of
      microleakage (P < .001). The results indicate that fluids and small molecules are
      capable of passing through the interface of all the A-I assemblies studied.
      Presumably in an in situ situation, fluids containing bacterial byproducts and
      nutrients required for bacterial growth may pass through the interface gap,
      contributing in part to clinically observed malodor and peri-implantitis.

PMID- 10074759
TI  - Five-mm-diameter implants without a smooth surface collar: report on 98
      consecutive placements.
AB  - In recent years, indications for endosseous dental implants have been extended to
      include partially edentulous jaws with areas of limited bone density and bone
      volume. Wide-diameter implants are particularly well suited for these situations.
      The purpose of this paper was to report on 98 consecutively placed 5-mm-diameter
      implants without smooth surface collars. Eight implants failed-6 at second-stage
      surgery, and 2 after 1 year of loading (91.8% survival rate). Sixty percent of
      the remaining implants had no thread above the bone level after 1 year of
      loading. The authors discuss the possible causes for failure and suggest
      guidelines to avoid failure.

PMID- 10074760
TI  - Ultrastructural immunohistochemical study of interstitial collagenous components
      of the healthy human keratinized mucosa surrounding implants.
AB  - The aim of this study was to investigate the ultrastructural and
      immunohistochemical organization of the main collagenous components of healthy
      human keratinized mucosa surrounding endosseous implants. Eight patients with
      completely edentulous mandibles were selected. Four endosseous implants were
      placed in the mandible of each patient, connected with a bar to support a
      complete overdenture, and loaded 4 months later. Two years after placement,
      biopsies of surrounding soft tissue, including the sulcular and junctional
      epithelium with the underlying and supracrestal connective tissue, were routinely
      prepared for standard electron microscopy and for ultrastructural immunolabeling
      of Types I, III, and IV collagen. The connective tissue located under the
      junctional epithelium comprised Types I and III collagen, whereas the
      supracrestal connective tissue was composed mainly of Type I collagen. Type IV
      collagen was located exclusively in the basement membrane of the junctional
      epithelium.

PMID- 10074761
TI  - Histologic evidence of osseointegration in the irradiated and reconstructed
      mandible: a case report.
AB  - Osseointegrated implants are widely used in dental rehabilitation. They are
      particularly valuable if the structures supporting a denture had to be removed
      because of oral cancer. Additionally, many of these patients undergo
      radiotherapy, but cancer and radiotherapy are seen as relative contraindications
      for implant therapy. In the literature, there are few clinical studies
      documenting successful oral rehabilitation using implants in such patients. The
      authors report a clinical case in which histologic evidence of osseointegration
      can be demonstrated in an irradiated and reconstructed mandible. This observation
      should encourage the extended application of implants in rehabilitation following
      oral cancer surgery.

PMID- 10074762
TI  - Rehabilitation of patients with reconstructed mandibles using osseointegrated
      implants: clinical report.
AB  - Experience with 9 patients who underwent mandibular reconstruction with
      autogenous free bone grafts and subsequent placement of titanium screw-type
      implants is reported. The interval between bone grafting and implant placement in
      these patients ranged from 8 to 34 months. A total of 33 implants was placed,
      followed up for 16 to 53 months, and achieved an 85% survival rate. Analysis of
      these patients reveals that the type of bone graft used is integral to successful
      prosthodontic reconstruction to ensure viability and minimal resorption as well
      as the timing of implant placement.

PMID- 10074763
TI  - Factors affecting heat generation during implant site preparation: a review of
      biologic observations and future considerations.
AB  - Atraumatic preparation of the recipient site has been considered an important
      factor influencing implant survival. Heat generation during bone drilling has
      been reported to be related to various factors. The methodology for heat
      assessment and bone examination together with the osseous models are still points
      of great speculation. The present paper classifies and discusses some of those
      factors in detail from both biologic and clinical perspectives. The methods of
      heat assessment and bone examination are reviewed, and the advantage and the
      limitations of each technique are presented. Future considerations based on
      clinical data reported are suggested.

PMID- 10074764
TI  - Cemented versus screw-retained implant prostheses: which is better?

PMID- 10074765
TI  - [New objectives in hypertensive therapy].

PMID- 10074766
TI  - [Sleep physiology and sleep disorders].

PMID- 10074767
TI  - [Sleep and old age].

PMID- 10074768
TI  - [Dreams. No senseless neuronal activity].

PMID- 10074769
TI  - [Nutrition and carcinogenesis].

PMID- 10074770
TI  - [Neuroleptics in late dyskinesia?].

PMID- 10074771
TI  - Employee health insurance/discrimination rules.

PMID- 10074772
TI  - Billing Medicare for incident-to services.

PMID- 10074773
TI  - Health care insurance premiums project.

PMID- 10074774
TI  - Toward physician-assisted living. Improving end-of-life care.

PMID- 10074775
TI  - Fraud and abuse. Understanding definitions and establishing compliance.

PMID- 10074776
TI  - Time to contemplate? A look ahead to an action-packed year.

PMID- 10074777
TI  - Anatomy and function of extrahypothalamic vasopressin systems in the brain.
AB  - The most prominent sites of vasopressin (VP) production in the rat brain are the
      paraventricular nucleus, the supraoptic nucleus, the suprachiasmatic nucleus, the
      bed nucleus of the stria terminalis (BST), and the medial amygdaloid nucleus
      (MA). Recently a number of new sites have been suggested, including the
      hippocampus, the diagonal band of Broca, and the choroid plexus. This chapter
      shows how differential regulation of these VP systems can be exploited to
      identify the contributions of individual VP systems to the various central
      functions in which VP has been implicated. It will focus on the development,
      anatomy, and function of the sexually dimorphic VP projections of the BST and MA.
      This system contains more cells and has denser projections in males than in
      females. This system is also extremely responsive to gonadal steroids as it only
      produces VP in the presence of gonadal steroids. It has been implicated in
      sexually dimorphic functions such as aggressive behavior as well as in non
      sexually dimorphic functions such as social recognition memory. Using comparative
      studies done in prairie voles as an example, this chapter makes the case that the
      VP projections of the BST and MA may simultaneously generate sex differences in
      some brain functions and behaviors and prevent them in others.

PMID- 10074778
TI  - Functions of the perikaryon and dendrites in magnocellular vasopressin-secreting
      neurons: new insights from ultrastructural studies.
AB  - Magnocellular hypothalamic neurosecretory neurons secreting vasopressin or
      oxytocin provide a robust model system for the investigation and understanding of
      many aspects of peptidergic neuronal function. Many of their functions and the
      cellular organelles involved are well understood. However, recent ultrastructural
      studies have thrown new light on various aspects of magnocellular neurosecretory
      function which have not previously received much attention. This review concerns
      two of these: the effects of mutations in the vasopressin gene on the handling of
      the translated peptide by the rough endoplasmic reticulum; and the role of the
      magnocellular dendrites in the production, secretion and localisation of
      peptides. Investigation of the synthesis of proteins derived from vasopressin
      genes which have undergone various mutations has at the moment provided more
      answers than questions: Why do some abnormal products accumulate as masses of
      peptide in the rough endoplasmic reticulum while others do not? Why do
      accumulations in humans appear to be damaging to the neurons while those in the
      rat do not? Investigations of the role of dendrites in the production and release
      of peptides show that the dendrites have all the machinery needed for protein
      translation and appear to synthesize locally proteins required for dendritic
      function. Of particular interest is the possibility that various transmitter
      receptor proteins could be synthesized in the dendrites close to the synapses in
      which they become localized. Precisely how such membrane proteins are inserted
      into the synaptic complex is, however, unclear, because the most part of the
      dendrites lack any form of the Golgi packaging organelle that can be recognised
      as such either by immunocytochemistry or electron microscopy. Better established
      is the ability of magnocellular dendrites to secrete either vasopressin or
      oxytocin in response to a variety of stimuli including sex steroids. This local
      release of peptide into the magnocellular nuclei has important but as yet
      incompletely defined effects on the functioning of the neurons.

PMID- 10074779
TI  - Functional neuroanatomy of the parvocellular vasopressinergic system:
      transcriptional responses to stress and glucocorticoid feedback.
AB  - This chapter summarizes the regulation of vasopressin (VP) transcription within
      the parvocellular neurosecretory cells of the hypothalamic paraventricular
      nucleus in vivo, with special reference to stress-response and glucocorticoid
      feedback. VP is commonly held as the first and the most potent among the co
      secretagogues that act synergistically with corticotropin-releasing factor (CRF
      41) to induce adrenocorticotropin (ACTH) from the anterior pituitary in response
      to various internal and external stimuli. Cellular levels of the primary
      transcripts of VP and CRF genes, revealed by in situ hybridization histochemistry
      using probes complementary to intronic sequences, are increased after acute
      challenges with different time courses. In contrast to the rapid stress-induced
      upregulation of CRF gene expression, VP transcription shows a delayed increase
      suggesting different regulatory mechanisms governing the two main ACTH releasing
      neuropeptides in the parvocellular neurosecretory neurons. With respect of
      transcription factors that may mediate these effects, besides rapid
      phosphorylation of the cAMP-response element-binding protein (CREB), VP
      activation in the parvocellular neurons requires additional newly synthesized
      factors such as those encoded by immediate-early genes, like c-fos. In addition,
      it has recently been revealed that glucocorticoid negative feedback during
      stress, selectively targets vasopressin transcription in the parvocellular
      neurons that is likely mediated by interaction of glucocorticoid receptors and
      immediate-early gene products. These data speak for the emerging consensus that
      VP is the principal factor that imparts situation-specific drive and represents
      the regulated variable governing hypothalamo-pituitary-adrenocortical axis during
      stress.

PMID- 10074780
TI  - Vasopressin binding sites in the central nervous system: distribution and
      regulation.
AB  - High affinity binding sites for vasopressin (VP) are widely distributed within
      the rat brain and spinal cord. Since their presence is associated with neuronal
      sensitivity to VP application, their anatomical distribution maps structures
      which could be activated by endogenous VP. Interestingly, marked species-related
      differences of the VP receptor distribution have been revealed. Some evidence has
      also been provided that mechanisms of receptor regulation may vary among species.
      In the rat, the expression of VP binding sites in some motor nuclei shows
      remarkable plasticity, in particular up-regulation after axotomy. These data
      suggest that VP may, in addition to affecting motoneuronal excitability, act as a
      trophic factor onto motoneurones.

PMID- 10074781
TI  - Osmoregulation of vasopressin neurons: a synergy of intrinsic and synaptic
      processes.
AB  - The release of vasopressin into the general circulation varies as a function of
      plasma osmolality and therefore plays a major role in systemic osmoregulation. In
      vivo, the secretion of this hormone in the neurohypophysis is primarily
      determined by the rate of action potential discharge of the magnocellular
      neurosecretory cells (MNCs) in the hypothalamus. Experiments done over the past
      20 years have clarified much of the neurophysiological basis underlying this
      important osmoregulatory reflex. As discussed here, recent findings indicate that
      the regulation of the firing rate of MNCs during changes in systemic osmolality
      involves the concerted modulation of mechanosensitive ion channels in MNCs, as
      well as excitatory glutamatergic inputs derived from forebrain regions such as
      the organum vasculosum of the lamina terminalis.

PMID- 10074782
TI  - Neurophysiology of magnocellular neuroendocrine cells: recent advances.
AB  - Magnocellular neuroendocrine cells of the hypothalamic paraventricular and
      supraoptic nuclei are responsible for most of the vasopressin and oxytocin in the
      peripheral blood as well as for central release of these peptides in selected
      brain areas. As the principal component of the hypothalamo-neurohypophysial
      system, these neurons have been a subject of continual study for half a century.
      The wealth of solid information from decades of in vivo studies has provided a
      firm basis for in vitro, brain slice and explant investigations of neural
      mechanisms involved in the control and regulation of vasopressin and oxytocin
      neurons. In vitro methods have revealed the presence and permitted the study of
      monosynaptic projections to supraoptic neurons from the olfactory bulbs, the
      tuberomammillary nuclei of the posterior hypothalamus and from the organum
      vasculosum of the lamina terminalis. Such methods have also facilitated the
      elucidation of the various ionic currents controlling neurosecretory cell
      activity as well as the roles of calcium binding proteins and release of calcium
      from internal stores. This review summarizes recent advances in our understanding
      of the afferent inputs that impinge upon these two cell types, and the cellular
      and molecular mechanisms intrinsic to these neurons that determine their activity
      patterns and, in part, their responses to incoming stimuli.

PMID- 10074783
TI  - Phenotypic and state-dependent expression of the electrical and morphological
      properties of oxytocin and vasopressin neurones.
AB  - Oxytocin and vasopressin secreting neurones of the hypothalamic supraoptic
      nucleus share many membrane characteristics and a roughly similar morphology.
      However, these two neurone types differ in the relative expression of some
      intrinsic and synaptic currents, and in the extent of their respective dendritic
      arbors. Spike depolarizing afterpotentials are present in both types, but more
      frequently give rise to prolonged burst discharges in vasopressin neurones.
      Oxytocin, but not vasopressin neurones, are characterized by a depolarization
      activated, sustained outward rectifier which turns on near spike threshold, and
      which can produce prolonged spike frequency adaptation. When this sustained
      current is deactivated by small hyperpolarizing pulses, a rebound depolarization
      sufficient to evoke short spike trains follows the offset of these pulses. Both
      oxytocin and vasopressin neurones exhibit a transient outward rectification
      underlain by an Ia-type current. This transient rectifier delays spiking to
      depolarizing stimuli from a relatively hyperpolarized baseline, and is more
      prominent in vasopressin neurones. As a result, oxytocin neurones may be more
      reactive to depolarizing inputs. Both cell types receive glutamatergic,
      excitatory synaptic inputs and both possess R,S- alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor
      subtypes. The AMPA receptor channel on both cell types is characterized by a
      relatively high calcium permeability and voltage-dependent rectification,
      characteristic of a diminished presence of the GluR2 AMPA subunit. However, AMPA
      mediated synaptic transients are larger, and decay faster, in oxytocin compared
      with vasopressin neurones, suggesting a potential difference for synaptic
      integration. The characteristics of NMDA-mediated synaptic transients are similar
      in oxytocin and vasopressin neurones, but some data suggest NMDA receptors may be
      less involved in the glutamatergic activation of oxytocin neurones. In both cell
      types, synaptic release of glutamate often coactivates AMPA and NMDA receptors.
      The dendritic morphology of oxytocin and vasopressin neurones in female rats
      differs from one another and exhibits considerable plasticity as a function of
      endocrine state. In virgin rats, oxytocin neurones have more dendritic branches
      and a greater total dendritic length compared with lactation, when the arbor is
      much less extensive. A complementary change occurs in vasopressin dendrites,
      which are more extensive during lactation. This reorganization suggests that
      oxytocin neurones may be more electronically compact during lactation. In
      addition, such dramatic shifts in overall dendritic length imply that significant
      gains and losses in either the total number of synapses, or in synaptic density,
      are incurred by both cell types as a function of reproductive state.

PMID- 10074784
TI  - The magnocellular neurons of the hypothalamo-neurohypophyseal system display
      remarkable neuropeptidergic phenotypes leading to novel insights in neuronal cell
      biology.
AB  - For decades the magnocellular neurons of the hypothalamo-neurophypophyseal system
      (HNS), in which either vasopressin or oxytocin are produced and released into the
      bloodstream, have been playing a pivotal role in fundamental discoveries in the
      nervous system. The primary structure of vasopressin and oxytocin was the first
      of all neuropeptides to be published, i.e., in the 1950s by the Nobel prize
      laureate Du Vigneaud. Moreover, many trend-setting discoveries have their origin
      in the HNS, which abundantly expresses vasopressin and oxytocin, clearly displays
      its function and is relatively easily to manipulate. Examples are the phenomenon
      of coexpression of neuropeptides, patch-clamping of nerve endings, axonal
      transport of RNA, neuroglia interactions and the behavioral effects. An
      extraordinarily intriguing example is the homozygous Brattleboro rat, which lacks
      vasopressin by a germ-line mutation, and has disclosed many of the fundamental
      characteristics of peptidergic neurons, and neurons in general. In this chapter
      we will discuss a few of them, in particular the recent data on mutations in
      vasopressin RNA. It is to be expected that the HNS will retain its informative
      role in the next decades.

PMID- 10074785
TI  - Biochemistry of vasopressin fragments.
AB  - Vasopressin (VP) undergoes a step-wise aminopeptidase conversion process in the
      brain, leading to accumulation of several metabolites. Some of these metabolites,
      in particular [pGlu4,Cyt6]VP 4-9 and 4-8, show behavioral effects comparable to
      VP, but are more potent and selective than VP. Most data favor the existence of a
      separate receptor for the VP metabolites distinct of the classical VP and
      oxytocin receptors, although its identity has remained obscure thus far. The
      characterization of this receptor is a major challenge to understand how the
      brain VP system generates and regulates divers central functions.

PMID- 10074786
TI  - Regulation of the synthesis and secretion of vasopressin.
AB  - We have developed a transgenic system that, for the first time, facilitates the
      monitoring of the regulatory dynamics of a central peptidergic system from
      transcription of a neuropeptide gene to the storage and release of the mature
      secretory product. Here we describe novel studies on the regulation of this
      system by physiological stimuli. The rat hypothalamic vasopressin (VP) mRNA
      responds in two ways to the functional demand imposed by an osmotic challenge.
      Firstly, the abundance of the VP RNA increases, and secondly, the size of the VP
      transcript increases as a consequence of a lengthening of the poly(A) tail. We
      have previously shown that chronic ingestion of 6-n-propyl-2-thiouracil (PTU),
      while not affecting plasma osmolality or VP mRNA size, results in a significant
      increase in the abundance of the hypothalamic VP mRNA. We now show that chronic
      PTU ingestion results in a dramatic increase in the abundance of the mRNA encoded
      by a modified rat vasopressin transgene that is expressed in rat vasopressinergic
      magnocellular neurons. This is accompanied by a significant depletion in neural
      lobe stores of a VP. However, this increase in transgene expression is
      accompanied by an increase in the proportion of transgene encoded products
      reaching the neural lobe--the pituitary content of a unique peptide encoded by
      the modified transgene does not change. These observations are further evidence
      in support of models of neurohypophyseal homeostasis that suggest that pituitary
      VP peptide levels passively reflect changes in hormone release and synthesis and
      that the availability of mRNA is the primary determinant of pituitary VP content
      in the basal state.

PMID- 10074787
TI  - Signal transduction pathways of the human V1-vascular, V2-renal, V3-pituitary
      vasopressin and oxytocin receptors.
AB  - Vasopressin (VP) and oxytocin (OT) are cyclic nonapeptides whose actions are
      mediated by stimulation of specific G protein-coupled receptors (GPCRs) currently
      classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) VP
      receptors and OT receptors (OTR). The recent cloning of the different members of
      the VP/OT family of receptors now allows the extensive characterization of the
      molecular determinants involved in ligand binding and signal transduction
      pathways coupled to a given VP/OT receptor subtype in stably transfected
      mammalian cell lines. In this article, we review the present knowledge of the
      signal transduction pathways coupled to the different VP/OT receptor subtypes and
      we present new observations derived from the study of each human VP or OT
      receptor subtype stably expressed in CHO cells.

PMID- 10074788
TI  - Function and molecular basis of action of vasopressin 4-8 and its analogues in
      rat brain.
AB  - VP 4-8 as a highly potent behavioral-active metabolite of arginine-vasopressin
      (VP) has been studied in detail at four levels, i.e. ligand level, membrane
      binding level, intracellular level and nuclear level. The purpose of this chapter
      is to review and discuss the main results obtained from our recent
      pharmacological and biochemical investigations which are described as follows: 1,
      structure-function relationship of VP 4-8 and its analogs; 2, some characters of
      VP 4-8-specific binding, the distribution of the binding sites in the rat brain
      and the consequent effect on long-term potentiation of synaptic transmission; 3,
      a putative receptor-mediated signaling pathway involving second messenger IP3,
      immediately-early gene c-fos transcription and protein kinase PKC, CaMKII and
      MAPK; 4, peptide-induced enhancement of some crucial functional proteins such as
      calmodulin, nerve growth factor (NGF) and brain-derived nerve growth factor
      (BDNF). The physiological significance of the events following VP 4-8
      administration and particularly, its possible role in learning and memory
      processes are discussed.

PMID- 10074789
TI  - Vasopressin in the mammalian brain: the neurobiology of a mnemonic peptide.
AB  - We have sought to understand the mechanisms by which VP can enhance memory
      function and in the process determine whether VP fulfills the requirements for
      neurotransmitter status. The latter goal of proving the neurotransmitter status
      of VP has been achieved through our findings and the results of many of the
      scientists contributing to this volume. With respect to elucidating the
      mechanisms by which VP can enhance memory function, results of our work have
      shown that VP and its receptors are present in brain regions known to be involved
      in memory function, that release of VP is inhibited by a factor that inhibits
      memory function, that VP can significantly enhance the morphological complexity
      and outgrowth of neurons involved in memory function, that second messenger
      systems held to be involved in learning and memory, cyclic AMP and calcium
      signaling pathways, are potentiated and activated by VP, that
      electrophysiological models of memory function are induced by VP, and that when
      animals remember a learned association VP content in brain increases over time
      during the active phase of remembering. Collectively, these studies have taught
      us a great deal about the sites and mechanisms of VP action and have led us to
      pursue avenues of investigation that we would not have imagined 15 years ago when
      we began this work. We stand on the threshold of a new era in our research as we
      begin our studies of the role VP and its receptors play in the cerebral cortex.
      Thus far, results of these studies are quite exciting and promise to yield
      fascinating insights into the complexities of VP action in the most highly
      developed region of the mammalian brain, the cerebral cortex, the site of
      abstract reasoning, judgment, complex analysis and the repository of those
      memories that last a life-time.

PMID- 10074790
TI  - Release of vasopressin within the brain contributes to neuroendocrine and
      behavioral regulation.
AB  - In addition to its peripheral secretion from the neurohypophysis, the
      neuropeptide vasopressin (VP) is released within the mammalian brain from
      probably all parts of the neuronal membrane. In particular the development of
      brain microdialysis in vivo together with blood microdialysis or blood sampling
      provides the advantage of being able to reliably compare the dynamic release
      patterns into different compartments of the organism. The central VP release
      within hypothalamic (e.g., supraoptic, paraventricular and suprachiasmatic
      nuclei) and limbic (e.g., septum, amygdala) rat brain areas is stimulated by a
      variety of substances and stressors, including interleukin-1 beta, social defeat
      and forced swimming. Furthermore, it is characterized by positive and negative
      feedback mechanisms and the capacity of the VP system for co-ordinated or
      independent release, the latter being observed, for example, during social
      defeat. This emotional stressor, in contrast to exposure to a novel cage,
      increased VP release within the supraoptic nucleus, but not into plasma. This
      failure to release VP peripherally could be observed also during forced swimming,
      despite a dramatic rise in plasma osmolality and a markedly stimulated central
      release. In another series of experiments we studied the effects of centrally
      released VP on cognitive and emotional aspects of behavior using reverse
      microdialysis for antagonist administration during the behavioral tests and
      antisense targeting to downregulate either VP or its local V1 receptor subtype.
      In this way, centrally (in particular septally) released VP could be shown to be
      causally involved in short-term memory and anxiety-related behavior. Furthermore,
      VP release within the hypothalamic paraventricular nucleus is likely to provide a
      negative tonus on the activity of the hypothalamic-pituitary-adrenocortical axis.
      This neuroendocrine effect together with cognitive, emotional and immunological
      effects of centrally released VP is thought to be essential to ensure adequate
      behavior of the animal during challenging situations and to contribute to the
      development of efficient coping strategies.

PMID- 10074791
TI  - Vasopressin and sensory circumventricular organs.
AB  - The subfornical organ, the area postrema and the organum vasculosum of the lamina
      terminalis are considered to be sensory circumventricular organs as they contain
      neuronal somata which are located outside the blood-brain barrier and are thus
      capable of serving as 'sensors' for blood-borne humoral messengers. The endocrine
      hormone, vasopressin (VP), not only causes strong antidiuresis by acting on the
      kidney, but also exerts centrally mediated effects as a neuromodulator. Several
      lines of evidence suggest that VP can influence regulatory functions mediated by
      the sensory circumventricular organs, since vasopressinergic somata and terminals
      as well as VP receptors have been reposted to be present in these structures.
      These biochemical prerequisites offer the possibility that blood-borne VP might
      on the one hand act as a feedback signal from the periphery and, on the other
      hand, synaptically released or locally produced VP could modulate the known
      functions of sensory circumventricular organs, such as thirst, fever or
      cardiovascular regulation. This review focuses on the possible physiological
      relevance of VP acting on sensory circumventricular organs in view of recent
      evidence obtained from biochemical and electrophysiological studies at the
      cellular level.

PMID- 10074792
TI  - Steroid hormone regulation of vasopressinergic neurotransmission in the central
      nervous system.
AB  - Vasopressinergic neurotransmission is intimately linked to steroid hormone
      signaling. Both arginine vasopressin (VP) and the extrahypothalamic VP V1a
      receptors are regulated by steroid hormones. Here, we present work that has been
      done in our laboratory, investigating mechanisms underlying steroid hormone
      effects on the expression of both VP and its primary receptor in the brain, the
      VP V1a receptor. Data on VP receptors, their coupling to second messenger
      pathways, their localization in brain, and their regulation by peptide exposure
      are discussed. We also cover the regulation of the V1a receptor by adrenal
      hormones, and the molecular basis of this effect. Evidence for the existence of
      other receptors for VP in the brain is presented. Lastly, the regulation of the
      VP peptide by gonadal hormones is discussed at the transcriptional level in the
      rodent brain. Finally, the potential significance of the 'cross-talk' between the
      vasopressinergic system and the steroid hormone system is addressed.

PMID- 10074793
TI  - Vasopressin and oxytocin action in the brain: cellular neurophysiological
      studies.
AB  - During the last two decades it has become apparent that vasopressin (VP) and
      oxytocin (OT), in addition to playing a role as peptide hormones, also act as
      neurotransmitters. Morphological studies and electrophysiological recordings have
      shown a close anatomical correlation between the presence of these receptors and
      the neuronal responsiveness to VP or OT. These compounds have been found to
      affect membrane excitability in neurons located in the hippocampus, hypothalamus,
      lateral septum, brainstem, spinal cord and superior cervical ganglion. Sharp
      electrode intracellular and whole-cell recordings, done in brainstem motoneurons,
      have revealed that VP and OT can directly affect neuronal excitability by opening
      non-specific cationic channels. These neuropeptides can also influence synaptic
      transmission, by acting either postsynaptically or upon presynaptic target
      neurons or axon terminals. Whereas in some hypothalamic neurons OT appears to
      mobilize intracellular calcium, as revealed by calcium imaging techniques, in the
      brainstem the action of this neuropeptide is mediated by a second messenger which
      is distinct from the second messenger activated in peripheral target cells.
      Future studies should be aimed at elucidating the properties of the cationic
      channels responsible for the neuronal action of VP and OT, at identifying the
      brain-specific second messengers activated by these neuropeptides and at
      determining whether endogenous VP and OT can exert neuronal effects similar to
      those elicited by exogenous neuropeptides.

PMID- 10074794
TI  - Vasopressin acting at V1-type receptors produces membrane depolarization in
      neonatal rat spinal lateral column neurons.
AB  - Vasopressin-immunoreactive fibers have been visualized in the area of spinal
      lateral horn cells, including spinal sympathetic preganglionic neurons. The
      presence and nature of vasopressin receptors on neurons in this area were
      addressed using whole-cell patch-clamp techniques in transverse spinal cord slice
      preparations from neonatal rat. Bath applications of Arg8-vasopressin (VP)
      induced a slow-onset membrane depolarization accompanied by spike discharges and
      membrane oscillations. In voltage-clamp, applications of VP induced a reversible,
      tetrodotoxin-resistant and dose-dependent inward current in 90% of tested cells.
      This effect was blocked by a V1 receptor antagonist [D-(CH2)5 Tyr (Me)-VP],
      whereas a V2 receptor agonist [desamino-(D-Arg8)-vasopressin] was ineffective.
      Furthermore the applications of oxytocin produced significantly smaller
      depolarizations when compared with VP suggesting that, at least in the neonatal
      lateral horn cells, vasopressin rather than oxytocin is more effective ligand.
      Both the amplitude and duration of the VP effect were enhanced after
      intracellular dialysis with GTP-gamma-S, a non-hydrolyzable GTP analogue, whereas
      the inward current was significantly reduced after intracellular dialysis with
      GDP-beta-S, a stable analogue of GDP that competitively inhibits G-proteins. The
      observation that the VP-induced net inward current reversed at a potential close
      to the equilibrium for potassium ions and was associated with a decrease in
      membrane conductance in a majority of tested cells suggest mediation through
      closure of a leak potassium conductance. These data indicate that SPNs and other
      lateral horn cells possess functional G-protein-coupled V1-type vasopressin
      receptors that, in adult spinal cord, may contribute to CNS regulation of
      autonomic nervous system function.

PMID- 10074795
TI  - Effects of vasopressin and related peptides on neurons of the rat lateral septum
      and ventral hippocampus.
AB  - The effects of vasopressin (VP), VP fragments and propressophysin glycopeptide on
      neuronal activities in the septum-hippocampus complex of rats were studied in
      vitro and in vivo. The frequency of the hippocampus theta rhythm in Brattleboro
      rats homozygous for diabetes insipidus was significantly slower than that of
      heterozygous litter mates and normal rats. Intracerebroventricular micro
      injection of des-glycine-amide vasopressin corrected for several hours the
      frequency deficit of the theta rhythm in the homozygous Brattleboro rats and the
      centrally administered VP slowed down theta rhythm in normal rats.
      Microinotophoretically administered VP excited single neurons in the lateral
      septum of ventral hippocampus, and/or facilitated the responses of these neurons
      to glutamate and to stimulation of the glutamatergic afferent fibers in the
      fimbria bundle. The excitatory effects of VP vanished within seconds after
      termination of the peptide administration, however, the peptide-induced
      enhancement of glutamate and syntatically induced excitations were sustained for
      up to 60 min after the peptide administration. In vitro, pM concentrations of VP,
      VP 4-8 and C-terminus glycopeptide of propresophysin facilitated for 30-60 min
      the glutamate-mediated EPSPs in neurons of the lateral septum or the ventral
      hippocampus. The EPSPs increase in the lateral septum neurons was not prevented
      by pretreatment with antagonist of the V1a type of the vasopressin receptor. The
      resting membrane potential and input resistance were not affected by the
      peptides. A low-frequency electrical stimulation in the diagonal Band of Broca or
      in the Bed nucleus of the stria terminals, sources of the vasopressinergic
      innervation of the septum, facilitated the negative wave of the filed potentials
      responses evoked in the lateral septum by stimulating the fimbria bundle fibers
      in control Long-Evans and Brattleboro rats heterozygous for diabetes insipidus.
      The field potential increase was sustained for several hours after the
      stimulation, and it was not occluded by long-term potentiation elicited by high
      frequency stimulation of the fimbria bundle afferent fibers. Brattleboro rats
      homozygous for diabetes insipidus failed to show the filed potential increase
      after the diagonal band stimulation. It is suggested that the long-lasting
      facilitation of glutamate-mediated excitations might be a physiological action of
      the propressophysin-derived peptides in the septum-hippocampus complex which, in
      concert with other forms of synaptic plasticity like the long-term potentiation,
      facilitates the hippocampus-mediated forms of learning and memory. This action is
      presumably related to the memory enhancing effect of the propressophysin-derived
      peptides.

PMID- 10074796
TI  - Electrophysiological studies of neurohypophysial neurons and peptides.
AB  - We have used hypothalamic slices of the supraoptic nucleus (SON) to investigate
      synaptic control of magnocellular vasopressinergic and oxytocinergic neurons.
      With the use of perforated patch recording techniques we identified and isolated
      excitatory or inhibitory postsynaptic currents elicited by electrical stimulation
      of afferent fibers. Both inhibitory and excitatory afferent fibers displayed
      presynaptic GABAB receptors; the GABAB agonist, baclofen caused a dose-dependent
      suppression of the evoked potentials in the absence of any effects on
      postsynaptic input resistance. Further evidence for a presynaptic locus included
      an increase in paired pulse ratio and a lack of effect on currents elicited by
      exogenously applied muscimol (a GABAA receptor agonist) or AMPA (a glutamate
      agonist). With the use of an GABAB receptor antagonist we demonstrated an action
      of endogenously released GABA, acting at GABAB receptors on excitatory terminals,
      to reduce excitatory transmission. In addition to presynaptic modulation by GABA
      of afferent inputs, we also observed actions of vasopressin and oxytocin,
      released from dendrites of magnocellular SON neurons, to gate afferent,
      excitatory transmission in the SON. Exogenously applied vasopressin and oxytocin,
      or these peptides when released by depolarizing stimuli of magnocellular neurons,
      reduced the size of evoked excitatory postsynaptic potentials at a presynaptic
      locus. We have also observed actions of arginine vasopressin to modulate the
      action of glutamate in slices of the ventral septal area and to attenuate a
      glutamate-mediated excitatory postsynaptic current in slices of the parabrachial
      nucleus.

PMID- 10074797
TI  - Electrophysiological effects of oxytocin within the bed nuclei of the stria
      terminalis: influence of reproductive stage and ovarian steroids.
AB  - The bed nuclei of the stria terminalis (BNST) is a target site for the central
      actions of oxytocin (OT) in promoting behavioural and neuroendocrine responses
      involved in female reproduction, and binding studies suggest that OT sensitivity
      may be modulated over the peripartum period. Electrophysiological recordings from
      brain slices in vitro showed that OT sensitivity of BNST neurones is relatively
      low in late pregnancy, but is high during lactation. In vivo studies over the
      immediate peri-partum period revealed that although BNST neurones can be excited
      by i.c.v. OT at day 22 of pregnancy, there is a 5-10 min delay in their response
      which is not present in lactation. This delay can be reversed by naltrexone, or
      lesioning the stria terminalis, and may involve an inhibitory opioid input to the
      BNST from the amygdala. Examination of the role of steroids in regulating OT
      responses of BNST neurones showed that oestradiol pre-treatment in late pregnant
      ovariectomized rats increased OT excitation of BNST neurones in vitro, and a
      similar result was observed with in vivo recordings. Progesterone also augmented
      OT excitation of BNST neurones in vitro, but no such effect was observed in vivo.
      This difference could indicate that an additional effect of progesterone is to
      potentiate extraneous inhibitory inputs to the BNST, or may reflect the ability
      of this steroid to suppress OT sensitivity by a direct membrane action. Changes
      in the response of BNST neurones to OT may have functional implications for the
      action of central OT in facilitating the neuroendocrine milk-ejection reflex
      (i.e. increasing milk-ejection frequency), an effect which first appears at
      around day 3 of lactation. Studies involving steroid treatment of late pregnant
      ovariectomized rats showed that this facilitatory mechanism can be induced to
      appear early (i.e. on day 22 of pregnancy) by oestradiol, but not progesterone
      treatment. Collectively, these results support this view, that the action of OT
      in the BNST is regulated by the changing levels of steroids towards the end of
      pregnancy, thereby ensuring appropriate neuroendocrine responses necessary for
      motherhood.

PMID- 10074798
TI  - Role of brain vasopressin in regulation of blood pressure.
AB  - Using recent advances in brain physiological, neurohistochemical, and molecular
      biological techniques, it could be demonstrated that the central action of
      vasopressin (VP) is important in cardiovascular regulation and in the
      pathogenesis of hypertension. VP is now known to be located in the area of the
      brain involved in cardiovascular regulation. Furthermore, in various
      pathophysiological states, brain VP secretion is regulated separately from the
      peripheral VP secretion system. The role of brain VP in the regulation of the
      circadian rhythm of blood pressure is becoming a topic of major interest.

PMID- 10074799
TI  - Vasopressin neurotransmission and the control of circadian rhythms in the
      suprachiasmatic nucleus.
AB  - Vasopressin (VP) is one of the principal transmitters in the suprachiasmatic
      nucleus (SCN). Approximately 20% of neurones in the dorsomedial division of the
      SCN synthesize the peptide and a high proportion of SCN neurones (> 40%) are
      excited by VP acting through the V1 receptor. This suggests that VP may act as a
      feedback regulator of electrical activity within the nucleus. Such an intrinsic
      excitatory signal can be demonstrated by perifusion with a V1 antagonist which
      reduces spontaneous neural activity. As the synthesis and release of VP occurs in
      a circadian manner, this leads to a variable feedback excitation which may
      contribute to the circadian pattern of activity of the neural clock. This role in
      amplifying rhythmicity is supported by observations that animals deficient in VP
      show a reduced circadian amplitude of behavioural rhythms (e.g. locomotor and
      cortical electroencephalographic rhythms). VP expression declines during ageing
      and although aged animals show no change in the proportion of SCN neurones
      excited by VP, the rhythm of spontaneous electrical activity shows a progressive
      decline, consistent with the reduced endogenous excitatory feedback. However, the
      homozygous Brattleboro rat which lacks any VP expression still maintains rhythms
      of electrical activity, indicating that VP is not the sole factor generating
      circadian activity. The generation of this rhythmicity may depend upon the
      interaction of VP with other transmitter systems, such as the inhibitory
      transmitters somatostatin and GABA which show a circadian variation in efficacy.
      In addition to its role in feedback amplification of the endogenous rhythm of
      electrical activity, VP also functions as part of the efferent signal to the rest
      of the CNS where it potentially regulates a number of behavioural and
      physiological rhythms, including the circadian activity of the hypothalamo
      pituitary-adrenal axis. Thus, the combined amplification and signalling functions
      makes VP an important component of the neuronal clock function in mammals.

PMID- 10074800
TI  - The suprachiasmatic nucleus-paraventricular nucleus interactions: a bridge to the
      neuroendocrine and autonomic nervous system.
AB  - Vasopressin (VP) is one of the principal neurotransmitters of the suprachiasmatic
      nucleus (SCN). By means of anatomical, physiological and electrophysiological
      techniques we have demonstrated that VP containing pathways from the SCN serve to
      affect neuroendocrine and 'autonomic' neurons in the paraventricular nucleus. By
      direct and indirect connections VP serves to inhibit corticosterone secretion,
      not only by affecting ACTH secretion but also by controlling the adrenal cortex
      via a neuronal route. Apart from controlling the pineal and adrenal, we also
      observed that the SCN is able to influence the heart. Subjecting rats or humans
      to light affects heart rate in a dose-dependent manner. These results suggest an
      important role for the SCN and VP in the SCN in the regulation of neuroendocrine
      and autonomic functions.

PMID- 10074801
TI  - Arginine vasopressin, fever and temperature regulation.
AB  - While central administration of arginine vasopressin (VP) to the non-febrile rat
      at high doses can cause hypothermia, there is little evidence for a role for
      endogenous VP in normal thermoregulation. In contrast, VP arising from cell
      bodies in the bed nucleus of the stria terminalis and innervating the ventral
      septal areas and possibly the amygdala appears to be an endogenous antipyretic,
      i.e. a substance capable of reducing fever. As the synthesis of VP in bed nucleus
      neurons is dependent upon circulating androgens, female rats have much less VP in
      these cells and their projections than do male rats. In keeping with this,
      females may make use of VP to a lesser extent than do males to bring about
      antipyresis. The phenomenon whereby the VP receptor can become sensitized by
      previous exposure to VP may be responsible for some states of endogenous
      antipyresis, in which fevers are suppressed through overactivity of the
      vasopressinergic system. States of endogenous antipyresis can be revealed around
      the time of parturition in both the neonate and the mother.

PMID- 10074802
TI  - Role of vasopressin and oxytocin in the control of social behavior in Syrian
      hamsters (Mesocricetus auratus).
AB  - Vasopressin (VP) and oxytocin (OT) play an important role in regulating social
      behavior in a variety of species as a result of their actions in the central
      nervous system. The following paper reviews the actions of VP and OT in
      controlling a range of social behaviors involved in communication, aggression and
      reproduction in the Syrian hamster. These data suggest that social and hormonal
      stimuli alter the expression of specific social behaviors by altering the release
      of, or the response to, VP and OT within key elements of the neural circuits
      controlling these behaviors.

PMID- 10074803
TI  - Vasopressin, gonadal steroids and social recognition.
AB  - Rodents exposed for a short amount of time to conspecific juveniles spend less
      time investigating familiar than unfamiliar juveniles. This is based on the
      formation of an olfactory image of juveniles, which involves an androgen
      dependent vasopressinergic pathway in males, as demonstrated by the ability of
      the vasopressin receptor antagonist dPTyr(Me)VP to block social recognition in
      intact male but not in female and castrated rats and mice. The involvement of
      sexually dimorphic vasopressinergic neurons appears to be dependent on the
      processing of social olfactory cues by the vomeronasal organ since removal of
      this organ in male rats mimics the effects of castration. These findings are
      discussed in relation to the role of vasopressin in learning and memory.

PMID- 10074804
TI  - Neurohypophyseal peptides and social recognition in rats.
AB  - An encounter between rats results in bouts of social investigation consisting
      mainly of sniffing, nosing, following and grooming. The assessment of social
      recognition is based on the tendency of rodents to investigate unfamiliar
      conspecifics more intensely, than familiar ones. In the laboratory an immature
      conspecific is normally used as the social stimulus because the use of juveniles
      eliminates possible sexual and/or aggressive behaviors of the rat whose memory is
      assessed. When a juvenile is presented for the first time, it is intensely
      investigated. A second presentation shortly after the first one elicits less
      attention. This is not due to satiation or fatigue, since the presentation of a
      novel juvenile triggers the full sequence of investigation. Social recognition is
      defined as a specific decrease in social investigation during the second
      encounter of the same individual. This form of memory is short lasting (< 40 min)
      and based on the olfactory characteristics of the stimulus animal. Social memory
      is prolonged by repeated exposure to the stimulus juvenile rat and is impaired by
      retroactively interfering stimuli. It can be facilitated by vasopressin and
      derivatives as well as by several other memory facilitating compounds, and,
      depending on the dose, attenuated or facilitated by oxytocin and derivatives.
      Ethologically oriented memory tests, that are based on olfactory characteristics
      of the information to-be-remembered, have an advantage over 'classical' ones:
      they estimate behavioral patterns which are important to an animal and not only
      to the investigator. Social memory paradigms can reveal information about memory
      processes in animals that is relevant for memory deficits in humans.

PMID- 10074805
TI  - Coping with stress in rats and mice: differential peptidergic modulation of the
      amygdala-lateral septum complex.
AB  - This chapter focuses on the parvicellular vasopressin (VP) system originating
      from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria
      terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number
      of limbic brain areas including the septum-hippocampal complex. Interestingly,
      this VP system is sexually dimorphic and the VP synthesis in this system depends
      on circulating gonadal steroids. Studies in rats and mice show that the variation
      in the lateral septal VP network within the male gender is as large as the
      variation between the sexes as reported in the literature. Non-aggressive males
      are characterized by a far more extensive VP network and a higher VP content in
      the lateral septal area than aggressive males. A review of the literature on the
      function of lateral septal VP in the organization of behavior reveals not only a
      modulatory role of behavior in a social context, but also of fear- and anxiety
      related behaviors. It is argued that these seemingly diverse functions might be
      explained by the concept of coping style. Extensive behavioral and physiological
      analyses in a variety of animal species show that males may be characterized by
      the way in which they cope with environmental challenges in general. Aggressive
      males tend to cope actively with their environment whereas non-aggressive males
      seem to accept the situation as it is more easily. In several tests, we
      determined the effects of chronic infusion of the V1 receptor antagonist locally
      into the lateral septal area in male rats. The main conclusion from these
      experiments is that LS VP does not modulate coping style in general. However, the
      experiments confirm the idea that LS VP has a certain degree of functional
      specificity in social behavior and social learning tasks. Together with the
      observation that the size and distribution of the vasopressinergic system may be
      highly variable between individual males in relation to their coping style, this
      suggests that the lateral septal vasopressinergic system is involved in the
      differential capacity of individuals to cope behaviorally with challenges of a
      social nature.

PMID- 10074806
TI  - Oxytocin and neuroadaptation to cocaine.
AB  - Oxytocin (OT) has been implicated in neuroadaptive processes such as learning,
      memory, and social-affiliative behavior as well as in the regulation of
      physiological responses leading to adaptation to the changing external and
      internal environment. Drugs of abuse constitute a major challenge to the
      homeostasis of the body and behavior. Drug tolerance, dependence and addiction
      may involve neuroadaptive mechanisms related to learning and memory at cellular
      and systems levels. Considerable effort has been made toward the understanding
      the neurobiological mechanisms of addictive behavior. Neuropeptides OT and
      vasopressin (VP) might be involved in these processes based on their effects on
      neuroadaptation and on their neuroanatomical localization and pharmacological
      actions. It has been demonstrated that both OT and VP have modulatory effects on
      opiate and alcohol tolerance and dependence. This chapter summarize the effects
      of OT, and in lesser extent VP, on neuroadaptation to cocaine, a psychostimulant
      drug of abuse. We have shown that OT inhibits acute cocaine-induced locomotor
      hyperactivity, exploratory activity and stereotyped behavior in rodents.
      Furthermore, OT facilitated, whereas VP inhibited the development of behavioral
      sensitization to cocaine. In a different model, OT inhibited the development of
      tolerance to the stereotyped behavior-inducing effects of cocaine as well as
      cocaine intravenous self-administration in rats. We demonstrated that OT acts
      through its specific receptors in the basal forebrain and in the hippocampus. OT
      and VP contents in the hypothalamus and limbic structures were altered by acute
      and chronic cocaine administration in a dose-dependent and region-selective
      manner. The differential plasticity of the brain OT-ergic and VP-ergic
      neurotransmissions in response to cocaine may underlie the differences in the
      involvement of these neuropeptides in cocaine addiction. Interaction of OT with
      dopaminergic neurotransmission in the nucleus accumbens, a key brain structure in
      drug addiction, as well as OT-ergic regulation of hippocampal processes may be
      among the mechanisms of action through which OT modulates neuroadaptation to
      cocaine. A better understanding of the role of OT in neuroadaptation to cocaine
      may provide an insight into both the mechanisms of neuropeptide actions in the
      brain as well as into the neurobiology of drug addiction.

PMID- 10074807
TI  - A peptidergic basis for sexual behavior in mammals.
AB  - Vasopressin (VP) is a peptide neurotransmitter in the limbic system of rats. It
      is synthesized in the medial amygdaloid nucleus in the presence of sex steroids,
      transported to other limbic structures such as the hippocampus and septum and
      secreted there by a calcium-dependent process. In the hippocampus, VP acts on
      cerebral microvessels and local circuit interneurons. Its excitatory action on
      the inhibitory interneurons produces near-total shutdown of electrical activity
      of the efferent fibers of pyramidal cells, the projection neurons of the
      hippocampus. Stimulation of the medial amygdala and release of the endogenous VP
      duplicates these effects and, since they are blocked by ventricular application
      of a VP antagonist, the effects are almost certainly mediated by endogenous VP.
      Recording from the VP-containing cell bodies or of the hippocampal action of the
      peptide indicates that the system is selectively involved with the early stages
      of sexual behavior, specifically those appetitive behaviors that anticipate
      coitus. Stimulation of the VP cells produces alterations in sexual behavior in a
      manner consistent with the hypothesis that the medial amygdala organizes the
      appetitive phase of recognition of an appropriate partner and sexual arousal.
      This role for the medial amygdala complements the proposed role of nearby
      structures in the consummatory, reward and learned aspects of sexual behavior.
      Association between VP, oxytocin (OT) and homologs with sexual behavior is very
      widespread among vertebrates, including amphibians, reptiles, primates and
      humans. Humans and other primates display a phenomenon called 'concealed
      ovulation' that may have played a role in the evolution of social structures. The
      review concludes with a discussion of possible experimental strategies for
      evaluating the possible role of VP in concealed ovulation and other conditions in
      which sexual behavior occurs outside of estrus.

PMID- 10074808
TI  - Voles and vasopressin: a review of molecular, cellular, and behavioral studies of
      pair bonding and paternal behaviors.
AB  - Several lines of evidence have implicated the neurohypophyseal peptide,
      vasopressin (VP), in the mediation of complex social behaviors including
      affiliation, aggression, juvenile recognition and parental behavior. Recent
      studies in microtine rodents using cellular, molecular and behavioral approaches
      provide additional evidence suggesting a role for VP in the formation of pair
      bonding and male parental care. Monogamous and promiscuous voles differ in social
      behaviors such as mating-induced pair bonding, selective aggression, and male
      parental care. Comparative studies have demonstrated that they also differ in
      dynamics of VP synthesis and release associated with reproduction, in the
      distribution pattern and regional quantity of VP receptors, and in the promoter
      sequence of the V1a receptor gene. In monogamous prairie voles, (Microtus
      ochrogaster), brain administration of VP induces pair bonding and male parental
      care whereas administration of the VP antagonist diminishes these behaviors.
      Together, these data suggest that VP is involved in the regulation of social
      behaviors in monogamous voles and differences in the brain VP system may underlie
      species differences in behavior and life strategy in voles.

PMID- 10074809
TI  - Role of vasopressin in learning and memory in the hippocampus.
AB  - The involvement of arginine8-vasopressin (VP) in learning and memory in the
      hippocampus is examined in mice using a discriminative learning task. Bilateral
      dorsal hippocampal lesion blocks the enhancing effect of intracerebroventricular
      (i.c.v.) injection of VP on retrieval and relearning processes. An additional
      study showed that immunoneutralization of dorsal hippocampal endogenous VP
      inhibited the facilitating effect of i.c.v. injection of VP, suggesting that
      hippocampus is essential for the expression of VP's behavioral effects. Using in
      situ microinjection, a greater sensitivity of the ventral part of the hippocampus
      to the memory enhancing effects of VP has been reported. This effect is mediated
      by vasopressin V1 type receptors and oxytocin receptors. Then, we examined the
      effects on behavior of VP applied to the ventral hippocampus, in relation to the
      time of treatment during learning. When the animals have no previous information
      about the task to learn, a deleterious effect of VP appears (pre-first session
      treatment). Regarding memory consolidation, the effects of VP may depend upon the
      previous level of performance acquired by the animals since, when injected after
      the first learning session, the peptide slightly delayed performance, whereas
      when the injection took place after the second learning session, it enhanced
      learning. Concerning memory retrieval, the effects of VP depend on the quality of
      the previously stored information. The fact that VP did not generate the same
      behavioral effects when the treatment was performed at the beginning or in the
      middle of the learning processes, suggests that mnemonic context is an important
      factor in understanding the effect of VP on memory in the ventral hippocampus.
      Finally, the role of hippocampal adrenergic receptors in the enhancing VP effects
      on memory retrieval has been examined. The facilitatory effects of VP seem to
      depend upon the functional state of both alpha- and beta-adrenergic receptors,
      but further studies will be necessary to clarify the role played by each receptor
      type in retrieval processes, and to determine the relationships that might exist
      between them.

PMID- 10074810
TI  - Vasopressin metabolites: a link between vasopressin and memory?
AB  - The effects of endogenous metabolites of the neuropeptide vasopressin (VP) in
      behavioural tests led to the hypothesis that VP metabolites have a more selective
      function than VP. In contrast to VP, no peripheral effects have been found thus
      far with VP metabolites and their function seems to be associated with memory
      related behaviour. VP metabolites can improve both consolidation and retrieval of
      memory. Effects on autonomic and electrophysiological parameters and interactions
      with other neurotransmitter systems have provided some information about the
      processes that could underlie the effects of VP metabolites on memory-related
      behaviour. There is evidence that the effects of VP metabolites could be mediated
      by a VP metabolite receptor, which is different from the known VP receptors. The
      VP metabolite receptor could be a link between the neuropeptide VP and memory
      related behaviour.

PMID- 10074811
TI  - Vasopressin in the locus coeruleus and dorsal pontine tegmentum affects posture
      and vestibulospinal reflexes.
AB  - Vasopressin (VP) acts on both the locus coeruleus (LC) neurons and the
      neighbouring dorsal pontine reticular formation (PRF) neurons by exciting them.
      Experiments performed in precollicular decerebrate cats have shown that
      microinjection of 0.25 x 10(-11) micrograms VP into the LC complex of one side
      increased the extensor rigidity of the ipsilateral limbs, while rigidity of the
      contralateral limbs remained unmodified or slightly decreased. The amplitude of
      modulation and thus the response gain of both the ipsilateral and the
      contralateral forelimb extensor triceps brachii to sinusoidal roll tilt of the
      animal (at 0.15 Hz, +/- 10 degrees), leading to stimulation of labyrinth
      receptors, decreased significantly, while there was only a slight decrease in
      phase lead of the responses. These effects occurred 5-10 min after the injection,
      were fully developed within 30 min and disappeared in about 2 h. VP activation of
      presumed noradrenergic LC neurons had a facilitatory influence on ipsilateral
      limb extensor motoneurons, either directly through the coeruleospinal (CS)
      pathway, or indirectly by inhibiting the dorsal PRF and the related medullary
      inhibitory reticulospinal (RS) neurons. Moreover, because the facilitatory CS
      neurons fire out-of-phase with respect to the excitatory VS neurons, we
      postulated that the higher the firing rate of the CS neurons in the animal at
      rest, the greater the disfacilitation affecting the limb extensor motoneurons
      during side-down animal tilt. These motoneurons would then respond less
      efficiently to the excitatory VS volleys elicited for the same direction of
      animal orientation, leading to a reduced gain of the EMG responses of the
      forelimb extensors to labyrinth stimulation. In contrast to these findings,
      unilateral injections of the same dose of VP immediately ventral to the LC, i.e.,
      in the peri-LC alpha and the surrounding dorsal PRF, where presumed cholinergic
      neurons are located, decreased extensor rigidity in the ipsilateral limbs while
      that of the contralateral limbs either decreased or increased. The same injection
      also produced either a moderate or a marked increase in gain of the multiunit EMG
      response of the ipsilateral triceps brachii to animal tilt. In the first instance
      the response gain of the contralateral triceps brachii to animal tilt increased
      slightly, while the corresponding response pattern remained unmodified, as shown
      for the ipsilateral responses (increased EMG activity during ipsilateral tilt and
      decreased activity during contralateral tilt). In the second instance, however,
      the response gain of the contralateral triceps brachii showed only slight
      changes, while the pattern of response was reversed. These effects occurred 5-20
      min after the injection, developed fully within 20-60 min and disappeared in 2-3
      h. We postulated that VP increased the discharge of the dorsal PRF neurons and
      the related medullary inhibitory RS neurons of the injected side, leading to
      reduced postural activity of the ipsilateral limbs. However, because these
      inhibitory RS neurons fire out-of-phase with respect to the excitatory VS
      neurons, it appeared that the higher the firing rate of the RS neurons in the
      animal at rest, the greater the disinhibition affecting the limb extensor
      motoneurons during ipsilateral tilt. These motoneurons would then respond more
      efficiently to the same excitatory VS volleys elicited by given parameters of
      stimulation, leading to an increased gain of the EMG responses. The contralateral
      effects could be attributed to crossed excitation by dorsal PRF neurons of one
      side, either of medullary inhibitory RS neurons or of excitatory CS neurons of
      the opposite side, respectively. We conclude that VP controls posture and gain of
      the VS reflex by acting on LC neurons as well as on dorsal PRF and the related
      medullary inhibitory RS neurons.

PMID- 10074812
TI  - The vasopressin deficient Brattleboro rats: a natural knockout model used in the
      search for CNS effects of vasopressin.
AB  - Behavioral neuroscience is using more and more gene knockout techniques to
      produce animals with a specific deletion. These studies have their precedent in
      nature. A mutation may result in a limited genetic defect, as seen in the
      vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a single
      pair of autosomal loci, and the sequences of VP gene from wild-type and
      homozygous Brattleboro rats are identical except for a single nucleotide deletion
      in the second exon. The deletion results in the synthesis of an altered VP
      precursor that is unable to enter the secretory pathway. The genetic disturbance
      results in a central diabetes insipidus comparable to that found in humans.
      Starting with our work during the early 1970s we found that the genetic defect in
      the availability of VP causes deficits in central nervous system (CNS) functions.
      Behavioral processes from cognition to drug tolerance appeared to be disturbed by
      the absence of VP, but not all behaviors are affected. The specificity of the
      absence of VP in causing behavioral deficits is shown in many cases. However,
      certain deficits are due to genetic factors other than the deletion of the VP
      gene. The picture is further complicated by differences in testing conditions,
      the absence of proper controls, i.e. heterozygous and wild-type Brattleboro rats,
      sex, compensation phenomena, and the absence of neuropeptides co-localized with
      VP. Interestingly, an age dependent spontaneous shunt to a heterozygous phenotype
      in vasopressinergic neurons might also compensate for the disturbance.
      Accordingly, findings in knockout animals should be interpreted with caution. One
      should realize that brain functions are modulated by multiple neuropeptides and
      that neuropeptides possess multiple CNS effects.

PMID- 10074813
TI  - The human hypothalamo-neurohypophysial system in health and disease.
AB  - The present paper reviews the changes observed in the human supraoptic (SON) and
      paraventricular (PVN) nuclei, and their projections to the neurohypophysis,
      median eminence and to other brain areas in health and disease.

PMID- 10074814
TI  - Neuropsychological effects of vasopressin in healthy humans.
AB  - Animal research indicated that vasopressin (VP) exerts its principle behavioral
      influence, the improvement of memory formation, through an action on septo
      hippocampal and connected limbic structures. Here human research is reviewed with
      the notion of a comparable effect of VP in healthy humans. Although the human
      studies yielded less consistent results than those in rats, they indicate that VP
      is able to improve declarative memory formation which is the type of memory
      essentially relying on hippocampal function. The effect appears to center on the
      encoding process for memory. In examinations of event-related brain potentials
      (ERPs) VP was consistently found to increase the 'mismatch negativity' (MMN) and
      the P3 components which are ERP potentials closely linked to the hippocampal
      processing of novel, unexpected and salient events. Enhanced processing of these
      stimulus aspects is considered to precipitate memory encoding. The regulation of
      voluntary selective attention and arousal do not appear to be primary targets of
      VP effects in humans. A mediation of effects by peripheral changes can be
      excluded since the central nervous effects were observed in studies using
      intranasal VP administration providing a direct access to brain functions.

PMID- 10074815
TI  - The Venn diagram: a metaphor for life.

PMID- 10074816
TI  - Bringing the population into focus: a natural development in community health
      nursing practice. Part I.

PMID- 10074817
TI  - Sharpening the focus on populations: an intentional community health nursing
      approach. Part II.
AB  - An interpretive study conducted in a Midwestern metropolitan area was designed to
      examine expertise in everyday community health nursing (CHN) practice. Twenty
      five nurses from three practice areas (traditional, nontraditional, and program
      development) participated in group and individual interviews and field
      observations, sharing stories of their practice. Transcribed interviews and field
      observation notes were analyzed as a text. One of the major findings of the study
      focused on experiences of the nurses as they developed the population aspects of
      their everyday practice. Part I describes the natural development of a population
      focus of CHN generalists whose care most often targeted individuals and families.
      The stories of how their practices evolved and were supported by their
      institutions provided insights into how nurses develop a broad population-focused
      practice perspective. Part II examines the practice of those CHN specialists who
      nurse their target populations from an intentional perspective. Their population
      focused practice, in which they repeatedly displayed what the research team terms
      multilingual and multiperspectival skills, was solidly based in their prior
      individual and family-focused experience and expertise in program planning and
      evaluation.

PMID- 10074818
TI  - Perceived ownership in a community coalition.
AB  - Coalitions are emerging as a force for change in many communities and offer the
      opportunity for broad community involvement in the planning and implementation of
      needed health promotion and health education services. Perceived ownership
      promotes greater participation by the community but efforts to systematically
      evaluate ownership are lacking. The aim of this study was to determine ownership
      of a local ElderCARE Coalition's activities and its health promotion program,
      Healthy WAY, as perceived by coalition members. Fifteen of the coalition members
      returned the questionnaire that included the Community Ownership Scale. As shown
      by mean scores, the agencies perceived as having the most influence or greatest
      perceived ownership were the university college of nursing and the community
      action programs. Coalition members represented a wide variety of roles and
      responsibilities as well as length of time in the coalition (1 month to 6 years).
      Responses to open-ended questions, analyzed by content analysis, supported the
      work of the coalition and identified the senior participants in the Healthy WAY
      program as being "enthusiastic" but also needing to be more "involved." Process
      measures are important indicators of how close coalitions are staying to their
      grassroots constituency. Implications for public health nurses include
      participating as partners in community coalitions and assisting coalitions in
      determining their sense of ownership and the need for change.

PMID- 10074819
TI  - African American women's experiences with physical activity in their daily lives.
AB  - Sedentary behavior is a major public health problem for African American women. A
      qualitative study used focus groups to explore African American women's
      experiences with physical activity in their daily lives. Women aged 35-50 were
      recruited to participate in the focus groups. Transcripts from the focus groups
      were coded and analyzed. African American women's facilitators of physical
      activity were daily routine, practical and convenient activities, personal
      safety, child care, weight loss, stress reduction, knowledge and commitment,
      enjoyment, pets, family and peer support, home and work facilities, and daylight
      and climate conditions. Barriers to physical activity were lack of child care, no
      person to exercise with, competing responsibilities, lack of space in the home,
      inability to use exercise facilities at work, lack of motivation, fatigue, and
      unsafe neighborhood. This information will provide the basis for generating new
      strategies to increase physical activity for African American women in the
      community.

PMID- 10074820
TI  - Tracking of avoidance of alcohol use and smoking behavior in a fifth grade cohort
      over three years.
AB  - This study examined the maintenance of positive health behavior (avoidance of
      alcohol use and cigarette smoking) and factors associated with the maintenance of
      these behaviors from fifth through seventh grade by a cohort of rural students (N
      = 232). African American and White students showed similar patterns of high
      avoidance of alcohol until seventh grade. Although more girls avoided use than
      boys, avoidance decreased in both groups with progression in grade. Mothers',
      fathers', and best friends' drinking behaviors influenced avoidance behavior;
      drinking was less likely to occur among those whose parents and friends did not
      drink. Friends' drinking behavior influenced alcohol use as early as fifth grade.
      Smoking avoidance was maintained by 74% of the students over the 3 years.
      Although there were no racial differences in smoking, African Americans started
      smoking about 1 year earlier than Whites. During seventh grade, an increase in
      smoking occurred among boys and girls, but was particularly striking among girls.
      Avoidance of smoking was influenced by mothers' behavior but not fathers'. Best
      friends' smoking behavior exerted a major influence on avoidance between grades 6
      and 7. In grades 5 and 6, those who avoided smoking were more physically active
      than smokers, but by seventh grade their physical activity declined to a similar
      level as smokers. Rural adolescent boys seemed to be at early risk for alcohol
      use and smoking, while rural girls delayed involvement by 1 to 2 years.
      Communities, schools, and families can help adolescents avoid alcohol use and
      smoking through early prevention efforts.

PMID- 10074821
TI  - "God brought all these churches together": issues in developing religion-health
      partnerships in an Appalachian community.
AB  - This study explored health-related and organizational religious activities in an
      Appalachian community and identified cultural issues in the development of
      religion-health partnerships. Partnerships between religious groups and health
      providers are a channel for health promotion efforts to vulnerable populations
      and must be approached from the culture of the community. An ethnographic,
      exploratory study of health-related and organizational activities in nonmainline
      religious groups yielded the use of prayer requests, anointing, testimonial, and
      denominational links as potential health resources. Organizational decisions were
      by congregational consensus and theological interpretation. The communal setting
      of worship as an informal resource to a community of believers, especially the
      vulnerable, was a viable model for religion-health partnerships in central
      Appalachia. Implications for nursing practice, education, and research also are
      addressed.

PMID- 10074822
TI  - From rhetoric to reality: the changing face of public health nursing in southern
      Ontario.
AB  - A feminist, postmodern oral history was undertaken to make visible the work and
      struggles of public health nurses in Southern Ontario in the midst of drastic
      cutbacks and dramatic changes in public health. The study focused on the period
      between 1980 and 1996, during which time two distinct practice modalities were
      apparent: district nursing and program-focused practice. The narrators' stories
      describe the nature of their work in both those modalities, the skills and
      expertise they demonstrated, and the often conflicting influences of medicine and
      the health promotion movement that dramatically changed their practice. District
      nursing was characterized by the public health nurse's integral connection with
      the community; program-focused practice, occurring at a time when political and
      economic factors also impacted on practice, was characterized by a loss of that
      integrality. Narrators saw many positive aspects to the changes in public health
      but identified problems as well. They articulated a preferred vision for the
      future as one in which "nurses should be nursing." To do that, public health
      nurses are challenged to return their practice to a nursing center rather than
      struggling to conform to dominant paradigms in public health.

PMID- 10074823
TI  - Changes in the work and motivation of staff delivering home care services in
      Finland.
AB  - This article describes how the policy to emphasize noninstitutional care is
      reflected in home care service strategies and work characteristics as well as the
      work motivation of home care staff in Finland. The data were gathered through a
      questionnaire answered by 312 employees in home care services and 22 social
      welfare and primary health care administrators. The methods of analysis used were
      cross-tabulations, one-way analysis of variance, and regression analysis.
      According to the results, institutional care had been reduced too fast and home
      care services had not been developed sufficiently. Most of the staff reported
      that their work had changed considerably. Although their work had become more
      interesting and more independent, over one third of the employees felt that the
      pressure of work had become unbearable and their responsibility was too heavy.
      The views of the home care staff differed from those of the administrators
      regarding the change strategies that had been carried out. The majority of the
      staff were moderately or highly motivated. Thirty-four percent of the variance of
      work motivation was explained mainly by work characteristics. More attention
      should be paid to the development of home care services before institutional care
      is reduced. Training the staff and informing them about the planned reform should
      not be neglected.

PMID- 10074824
TI  - The public health nurse in tornado relief.

PMID- 10074826
TI  - [The moment of freedom for the patients].

PMID- 10074825
TI  - [The firing of JAMA's editor is a shame for the American Medical Society].

PMID- 10074827
TI  - [Has the HOT study taught us something new?].

PMID- 10074828
TI  - [Listeria monocytogenes--an opportunist with serious intentions].

PMID- 10074829
TI  - [Telepathology in Mid-Norway].
AB  - Telepathology can provide frozen section service to hospitals without a pathology
      service of their own. Using a dynamic-robotic system with 6 ISDN B-channels
      (Telemed A200, AM Elektronikk A/S, Oslo, Norway), the pathologists at the
      University Hospital in Trondheim, Norway during a three-year period from 1995
      successfully performed 116 diagnostic sessions for two rural Norwegian hospitals.
      In 90% of the cases a diagnosis was provided. There was no false positive
      diagnosis and only 3% false negative cases without clinical consequence. Deferred
      cases (10%) were mainly due to poor quality of the frozen sections and a
      conservative attitude among the pathologists. It is concluded that the diagnostic
      accuracy is good, but for safety reasons telepathology should be offered on a
      regular basis, so that the skills of the technicians and pathologists involved
      are kept up. In Mid-Norway, five more hospitals will be included in a
      telemedicine network comprising eight hospitals in the region.

PMID- 10074830
TI  - [Gaining new knowledge in clinical practice].
AB  - A study of the diffusion of knowledge about Helicobacter pylori and
      gastrointestinal disease among Norwegian clinicians is reported. A questionnaire
      about when and how research results on Helicobacter pylori and gastrointestinal
      disease were taken up by doctors in their practice was sent to 200 general
      practitioners and 200 medical and surgical gastroenterologists. This Norwegian
      study is part of a comparative study of the uptake process in the five
      Scandinavian countries which is planned to be published in an international
      journal. The specialists both heard of research results and started using new
      treatments earlier than the general practitioners. The main sources of
      information for the general practitioners were the national medical journal and
      courses or conferences, whilst the specialists obtained their information mainly
      from international journals and courses or conferences. The general practitioners
      were more likely to treat Helicobacter pylori positive dyspepsia and to use
      serology as a diagnostic tool, whilst the specialists were more likely to use
      breath tests and had a greater belief in the role of Helicobacter pylori as a
      cause of gastric cancer. The great majority of both groups knew of Helicobacter
      pylori as a cause of peptic ulcer disease, used antibiotics in its treatment, and
      preferred (referral to) endoscopic biopsy as the main diagnostic tool.

PMID- 10074831
TI  - [Anal plug in fecal incontinence].
AB  - There is evidence that a considerable number of the adult population, most of
      them women (30-72 years), are suffering from faecal incontinence. Treatment is
      either conservative sphincter reconstruction or stoma when no other treatment is
      successful. As an alternative to stoma, the Conveen anal plug was tested in seven
      women not suitable for surgery. Three patients had substantially improved social
      life. One of these patients used the plug daily, the other two at specific
      occasions. The main advantages were that they did not have to use a pad and they
      were not bothered by inconvenient smell and sound. Four patients did not tolerate
      the plug because of urge to defecate and general inconvenience having the plug in
      the anal canal. The study confirms that the incontinence anal plug is a useful
      alternative to stoma in selected cases.

PMID- 10074832
TI  - [Prolonged half-life of digitoxin in the elderly].
AB  - Digitoxin is frequently used in Norway in the treatment of cardiac failure.
      Digitalis glycosides may give rise to a number of side effects difficult to
      separate from disease in the elderly. Six patients aged 77-93 years, treated with
      digitoxin 0.05 mg/day, were hospitalized due to digitalis intoxication. Mean
      digitoxin half-life was 25.2 days. This is significantly more than reported in
      other studies on younger patients. The symptoms of digitoxin intoxication
      disappeared on discontinuation of medication. The slow elimination of digitoxin
      may be related to reduced serum albumin concentration. When digitoxin is used in
      the treatment of heart failure in the very elderly patients, one should be aware
      of the possibility of digitoxin intoxication, even at a low dose.

PMID- 10074833
TI  - [Abdominal metastases from signet cell carcinoma of the appendix vermiformis].
AB  - Signet cell carcinomas are often aggressive tumours. A patient with this tumour,
      originally located in the appendix, was diagnosed with peritoneal metastases.
      When she later got abdominal symptoms, computer axial tomography indicated large
      infiltrating tumour masses in the pelvis. However, when a laparotomy was
      performed, the only macroscopic tumour masses was localised to the ovaries
      (Krukenberg tumour). The surgical intervention gave the patient an improved
      quality of life, and most likely prolonged survival. We stress the importance of
      thinking of this possibility.

PMID- 10074834
TI  - [Brain stem infection caused by Listeria monocytogenes].
AB  - Rhombencephalitis due to Listeria monocytogenes is a serious form of brainstem
      inflammation. It is difficult to diagnose on the basis of clinical and laboratory
      findings alone. We describe a fatal case of Listeria monocytogenes
      rhombencephalitis in a previously healthy female teenager. Clinical and
      pathogenetic aspects of this condition are discussed.

PMID- 10074835
TI  - [Listeria monocytogenes--the perfect parasite?].
AB  - The pathogen Listeria monocytogenes has an extraordinary intracellular life
      cycle, based on adaption to and exploitation of normal cellular mechanisms.
      Extracellular organisms induce their own phagocytosis, followed by destruction of
      the phagosomal membrane. Cytoplasmatic bacteria organize the intracellular
      protein actin into "comet tails", and thus gain motility. In contact with the
      plasma membrane, motile bacteria induce a pseudopodium, corresponding to an
      invagination of the plasma membrane of the neighbouring cell. Eventually, the
      pseudopodium is engulfed by the neighbouring cell, creating a double membrane
      vacuole. L. monocytogenes destroys the double membrane, and escapes into the
      cytoplasm. This article reviews the molecular biology of Listeria infection, and
      how research in this field has yielded increased insight into normal cellular
      processes. Finally, we propose that the neuroinvasive properties of L.
      monocytogenes is caused by actin-dependent transport within axons from the
      periphery to the central nervous system.

PMID- 10074836
TI  - [Frostbite injuries].
AB  - Frostbite injuries occur mainly in toes, fingers, ears, nose and cheek. Typically
      an initial vasoconstriction in the skin will protect from drop in core
      temperature. Ice crystal development occurs when tissue temperature drops to -2
      degrees C, leading to increased osmolality of the extracellular fluid and
      intracellular dehydration. An additional insult occurs with thawing due to
      reperfusion of the tissue and thereby release of inflammatory mediators. Symptoms
      of frostbite injury are: White-cyanotic discoloration, pain and numbness followed
      by hypoaesthesia. General hypothermia should be prevented and treated before
      managing the local frostbite injuries. Direct contact with warm skin without
      rubbing should be used in superficial injuries. More severe and deeper injuries
      should not be thawed until definite treatment could be given in a hospital. Re
      freezing and mechanical influence on the injured parts must be avoided. Thawing
      should preferably be done in stirred water of 40-42 degrees C with mild soap.
      Antibiotics may be indicated when the skin barrier is broken. Surgical
      debridement should be postponed until a clear demarcation occurs.

PMID- 10074837
TI  - [Climatic changes in Scandinavia--consequences for public health].
AB  - Atmospheric composition and climate conditions are of great importance for
      health. Increasing consumption of fossil fuels ever since the industrial
      revolution has resulted in higher contents of greenhouse gases in the atmosphere.
      Primarily, this will increase the global temperature. Secondarily, it may change
      the patterns of precipitation and droughts. Higher extreme temperatures will have
      a negative effect on health. Climate changes can also change the living
      conditions of undesirable insects and microbes. The ozone gas in the atmosphere
      acts as a shield against the harmful ultraviolet radiation from the sun.
      Chlorofluorocarbons contribute to reduction of the ozone layer and increase
      ultraviolet radiation. Increased exposure of the skin to this radiation may cause
      damage such as sunburn and skin cancer. In order to avoid damage, it is of
      importance to wear protective clothing or use effective sunshades.

PMID- 10074838
TI  - [Alternative medicine. Attitude of and survey by the Medical Society].

PMID- 10074839
TI  - [Are we really interested to find out if homeopathic therapy has any effect?].

PMID- 10074840
TI  - [Community medicine is dead, long live general medicine].

PMID- 10074841
TI  - [The HOT study].

PMID- 10074842
TI  - [Tonsillectomy and adenoidectomy].

PMID- 10074843
TI  - [New substances--new diagnostic challenges].

PMID- 10074844
TI  - [Hemorrhagic complications of spinal and epidural analgesia].

PMID- 10074845
TI  - [Central nervous system stimulants in adults with AD/HD].

PMID- 10074846
TI  - [Treatment of cardiac arrhythmia].

PMID- 10074847
TI  - [Choice of antibiotics in diarrhea due to Clostridium difficile].

PMID- 10074848
TI  - [Lung volume reduction surgery. A new surgical therapeutic possibility for
      patients with emphysema].
AB  - Lung volume reduction surgery is a new surgical procedure for treatment of
      patients with pulmonary emphysema. At the operation the most peripheral parts of
      the lung are resected. Only 15-20% of the patients admitted for lung volume
      reduction surgery are suitable for operation. The preliminary results have
      demonstrated improvement in lung function in the majority of the patients. Most
      of the reports comprise small numbers of patients and have a short time of
      observation. The longest reported period of observation for a larger number of
      patients is 24 months and shows a continuing improvement in lung function,
      dyspnoea and six minute walk test. Because of the high incidence of emphysema,
      lung volume reduction is a procedure that could reach large extension in the
      future. However, better definition of criteria of inclusion and better evaluation
      of the operative procedures are needed.

PMID- 10074849
TI  - [Arterial puncture or pulse oximetry?].
AB  - Arterial puncture is the general accepted standard method for monitoring oxygen
      therapy in critically ill patients, but this technique is painful for the
      patient, has the potential of complications, and does not provide immediate
      continuous data. Pulse oximetry is a non-invasive method used to measure arterial
      oxygen saturation with a clinically acceptable accuracy of +/- 2%. Despite some
      limitations, pulse oximetry is considered to be reliable in most cases in
      detecting hypoxaemia and monitoring oxygen therapy in stationary units. The pulse
      oximeter can reduce the number of arterial punctures, personnel's time
      consumption, and limit oxygen abuse. Furthermore the new transportable and hand
      held pulse oximeters offer new possibilities for continuous 24 hour monitoring of
      oxygen saturation also out of hospitals. The pulse oximeter can optimize
      monitoring patients' oxygen saturation in the stationary units, however, arterial
      puncture will remain the most reliable method in the assessment of hypoxaemia and
      hypercapnia, especially in acute situations.

PMID- 10074850
TI  - [Results of bat ear surgery over a period of ten years].
AB  - A material of 286 patients or 545 ears submitted to operation for protruding ears
      operated by Stenstroms and Nordzells surgical procedure over a period of ten
      years were reviewed retrospectively. One hundred and sixty-three patients were
      clinically investigated and interviewed. The mean observation time was eight
      years. Satisfactory results were obtained in 94% of the patients subjectively.
      Objectively there was a good result in 74% of the cases. Relatively few
      complications and reoperations occurred. However 20% of the patients interviewed
      had postoperative pain more than one year after the operation. The results of the
      operations are reviewed and discussed. There was no significant difference
      between the results of the surgical procedure a.m. Stenstrom and a.m. Nordzell.

PMID- 10074851
TI  - [Oral ranula. A follow-up study].
AB  - Ranula is a cystic swelling of the floor of the mouth, which is usually
      unilateral and relatively uncommon. The cyst arises from the sublingual salivary
      gland. We reviewed 14 patients operated in the period 1976-April 1998. There was
      no recurrence after marsupialization and after extirpation of the sublingual
      gland. Fourteen percent of the patients had recurrence after extirpation of the
      cyst. At the follow-up time (average 8.1 years) 18.2% had complications. We
      suggest that marsupialization/extirpation of the cyst should be primary
      treatment. In case of recurrence the sublingual gland should be extirpated.

PMID- 10074852
TI  - [Differences between male and female alcoholics and differences in their need of
      treatment].
AB  - The present study covers 375 consecutive patients referred to the three
      outpatient clinics at the Psychiatric Department of Odense University Hospital
      from November 1995 to February 1997. The aim of the study was to describe
      differences in problem profiles for men and women. All patients were assessed by
      means of the Addiction Severity Index at admission. All patients needed treatment
      for alcohol problems. Significantly more female alcoholics, however, had problems
      with mental health, physical health, drug use and family/social life. More men
      than women had legal problems. Almost half of the women had previously attempted
      to commit suicide, and almost one third of the women suffered from anxiety
      disorder at the time of admission. Significantly more women than men had partner
      who also had an alcohol problem.

PMID- 10074853
TI  - [Gallstones and pancreatic necrosis in acute pancreatitis].
AB  - The purpose of this study was to investigate the occurrence of gallstones and the
      severity of acute pancreatitis in a Danish population, and in severe cases, the
      relation between pancreatic necrosis and gallstones. We used Ranson's prognostic
      scoring system to measure the severity of acute pancreatitis, ultrasonography for
      detecting biliary stones, and computed tomography or laparotomy for detecting
      pancreatic necrosis. During a two year period, we registered 101 patients.
      Approximately 70% were mild cases, and we found 18 patients with and 53 patients
      without gallstones. Among patients with severe cases, we observed 14 with and 16
      without gallstones. There was a significantly higher proportion of gallstones in
      severe cases. Eight of 30 patients with severe pancreatitis had pancreatic
      necrosis, but we found no relation between the occurrence of necrosis and
      gallstones. We conclude that patients with gallstone related pancreatitis have
      more severe disease than patients without stones, but the complication of
      pancreatic necrosis is not related to gallstones.

PMID- 10074854
TI  - [Right bundle branch block, ST segment elevation and sudden cardiac death. A
      clinical and electrocardiographic syndrome--Brugada syndrome].
AB  - The association of an abnormal electrocardiogram (ecg) consisting of right bundle
      branch block and ST segment elevation in leads V1-V3 and sudden arrhythmic death
      has been described in patients with no demonstrable structural heart disease. A
      patient with these ecg findings and aborted sudden death is presented. The
      patient had no structural heart disease and received an implantable cardioverter
      defibrillator which seems to be the treatment of choice.

PMID- 10074855
TI  - [Psoas abscess in pyogenic sacroiliitis].
AB  - A 47-year-old man was admitted with septic fever over a few days. A CT-scan
      showed a psoas abscess, which was drained by surgery. In the meantime antibiotics
      were started. In spite of this treatment, he continued to have septic fever. Bone
      scintigraphy and MR-scan showed activity in the right sacroiliac joint compatible
      with sacroiliitis. The joint was opened surgically and revised. The patient was
      treated with antibiotics for nine weeks and was fully restituted. It must be
      concluded that the psoas abscess was secondary to the sacroiliitis, a rare event.

PMID- 10074856
TI  - [Efficiency of endoscopic therapy of varices. The significance of paraesophageal
      varices and perforating veins].

PMID- 10074857
TI  - [Picture of the month. Varicose veins].

PMID- 10074858
TI  - [Recommended regime in percutaneous biopsy of the liver].

PMID- 10074859
TI  - [Polyneuropathies].

PMID- 10074860
TI  - [Admission to the obstetric department versus ambulatory labor--seen from women's
      perspective].

PMID- 10074861
TI  - [Are psychiatric diseases brain diseases?].

PMID- 10074862
TI  - [What is in the heart comes out of the mouth].

PMID- 10074863
TI  - [Screening for hemoglobinopathy].

PMID- 10074864
TI  - [Gallstone management in Denmark II].

PMID- 10074865
TI  - [Rentolin wood-preserving oil--a toxicologic evaluation].

PMID- 10074866
TI  - Perceived overqualification and health: a longitudinal analysis.
AB  - The authors examined the effects of perceived overqualification on health and
      health decline by means of a 2-wave panel study of members of a midwestern
      American Postal Workers Union local. The 1st hypothesis was that
      overqualification was negatively related to health at Time 2 (T2); the second
      hypothesis was that overqualification was positively related to perceived health
      decline at T2. Neither was supported by the data. However, the relationships were
      in the expected direction for perceived mismatch but not for the perceived no
      grow dimension of overqualification. The results imply that perceived no grow may
      have immediate threats to health, whereas perceived mismatch may have longer term
      implications for health. The stability of perceived health between Time 1 (T1)
      and T2 could overshadow a longitudinal effect of overqualification on health and
      health decline at T2.

PMID- 10074867
TI  - Gender traits and identities in a "masculine" organization: the Israeli police
      force.
AB  - Gender and occupational identities were examined within the Israeli police force,
      a stereotypically masculine organization. The principal hypothesis was that women
      in this organizational setting did not reject their gender identity. Rather, they
      self-attributed more traditionally masculine traits in addition to their feminine
      traits. This was especially so among women going through particularly intense
      occupational and organizational socialization needed for field jobs. The findings
      only partially confirmed the hypothesis. Most women in the sample considered
      themselves to be highly feminine, even though they self-attributed masculine
      traits. Although the women, like their male colleagues, ranked occupational
      identity higher than gender identity, their feminine identity (usually in
      contrast with the masculine organizational context) was not repressed and their
      gender identity was as strong as that of the men.

PMID- 10074868
TI  - The strain of guardianship for men in the United States.
AB  - This study examined the extent to which control, commitment, and support
      influenced the strain experienced among men in the U.S. who were acting as
      guardians for aged adults, an atypical role for such men. A total of 146 male
      guardians responded to a questionnaire. Results of the study showed that control
      and commitment were associated with less strain, whereas the use of formal
      support systems was related to greater levels of strain. Additionally, strain was
      found to be less prevalent among older guardians.

PMID- 10074869
TI  - Personal or environmental causes of happiness: a longitudinal analysis.
AB  - The author analyzed an integrative model of happiness, which incorporated
      personal factors (demographics, extraversion, neuroticism, and locus of control)
      and environmental factors (life events and social support), using a longitudinal
      data set. A secondary purpose was to clarify the relationship between overall
      happiness and life satisfaction. Using systematic random sampling, 581 residents
      of Kaohsiung, Taiwan, completed structured questionnaires at Time 1; among them,
      105 returned valid questionnaires 2.5 years later, at Time 2. Longitudinal
      analysis indicated moderate stability of the subjective well-being (SWB)
      measures. More importantly, when both the baseline SWB levels and personality
      traits were statistically controlled, social support still predicted overall
      happiness, and positive life events predicted life satisfaction. Furthermore,
      there was a consistently strong bidirectional relationship between overall
      happiness and life satisfaction.

PMID- 10074870
TI  - Peptides and psychiatry, Part 1: How synthesis of neuropeptides differs from
      classical neurotransmitter synthesis.

PMID- 10074871
TI  - Clinical practice guidelines: praise and problems.

PMID- 10074872
TI  - Clinical practice guidelines for bipolar disorder from the Department of Veterans
      Affairs.
AB  - BACKGROUND: For the last several years, the Department of Veterans Affairs (VA)
      has been involved in the development of practice guidelines for major medical,
      surgical, and mental disorders. This article describes the development and
      content of the VA-Clinical Practice Guidelines for Bipolar Disorder, which are
      available in their entirety on the Journal Web site (http://www.
      psychiatrist.com). METHOD: A multidisciplinary work group composed of content
      experts in the field of bipolar disorder and practitioners in general clinical
      practice was convened by the VA's Office of Performance and Quality and the
      Mental Health Strategic Health Group. The work group was instructed in algorithm
      development and methods of evidence evaluation. Draft guidelines were developed
      over the course of 6 months of meetings and conference calls, and that draft was
      then sent to nationally prominent content experts for final critique. RESULTS:
      The Bipolar Guidelines are part of the family of the VA Clinical Guidelines for
      Management of Persons with Psychosis and consist of explicit algorithms
      supplemented by annotations that explain the specific decision points and their
      basis in the scientific literature. The guidelines are organized into 5 modules:
      a Core Module for diagnosis and assignment to mood state plus 4 treatment modules
      (Manic/Hypomanic/Mixed Episode, Bipolar Depressive Episode, Rapid Cycling, and
      Bipolar Disorder With Psychotic Features). The modules specify particular
      diagnostic and treatment tasks at each step, including both somatotherapeutic and
      psychotherapeutic interventions. CONCLUSION: The VA Bipolar Guidelines are
      designed for easy clinical reference in decision making with individual patients,
      as well as for use as a scholarly reference tool. They also have utility in
      training activities and quality improvement programs.

PMID- 10074873
TI  - Once-daily venlafaxine extended release (XR) compared with fluoxetine in
      outpatients with depression and anxiety. Venlafaxine XR 360 Study Group.
AB  - BACKGROUND: We conducted a randomized, double-blind, placebo-controlled study of
      the efficacy and safety of once-daily venlafaxine extended release (XR) and
      fluoxetine in outpatients with major depression and concomitant anxiety. METHOD:
      Patients who met DSM-IV criteria for major depressive disorder and satisfied
      eligibility criteria were randomly assigned to once-daily venlafaxine XR,
      fluoxetine, or placebo for 12 weeks. Efficacy was assessed with the Hamilton
      Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A),
      and Clinical Global Impressions scale. RESULTS: Among 359 outpatients,
      venlafaxine XR and fluoxetine were significantly superior (p < .05) to placebo on
      the HAM-D total score beginning at week 2 and continuing to the end of the study.
      Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2
      on the HAM-D depressed mood item. At week 12, the HAM-D response rate was 43% on
      placebo, 67% on venlafaxine XR, and 62% on fluoxetine (p < .05). The HAM-D
      remission rate was significantly higher (p < .05) at weeks 3, 4, 6, 8, 12, and
      final evaluation with venlafaxine XR and at weeks 8, 12, and final evaluation
      with fluoxetine than with placebo. The HAM-A response rate was significantly
      higher (p < .05) with venlafaxine XR than with fluoxetine at week 12. The
      incidence of discontinuation for adverse events was 5% with placebo, 10% with
      venlafaxine XR, and 7% with fluoxetine. CONCLUSION: Once-daily venlafaxine XR is
      effective and well tolerated for the treatment of major depression and
      concomitant anxiety and provides evidence for superiority over fluoxetine.

PMID- 10074874
TI  - Psychotic symptoms in combat-related posttraumatic stress disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is known often to be comorbid
      with other anxiety, mood, and substance use disorders. Psychotic symptoms have
      also been noted in PTSD and have been reported to be more common in Hispanic
      veterans. However, the occurrence of psychotic symptoms, including the degree to
      which they are accounted for by comorbid disorders, have received limited
      systematic investigation. Our study objectives were to assess psychotic symptoms
      according to DSM-III-R criteria in patients with a primary diagnosis of combat
      related PTSD and determine the associations of those symptoms with psychiatric
      comorbidity and ethnicity. METHOD: Fifty-three male combat veterans consecutively
      admitted to a PTSD rehabilitation unit were assessed for psychotic symptoms and
      Axis I disorders. Ninety-one percent were Vietnam veterans; 72% were white, 17%
      were Hispanic, and 11% were black. Associations between psychotic symptoms and
      comorbid depression, substance use disorders, and minority status were compared
      by chi-square analyses; associations between psychotic symptoms and both PTSD and
      dissociative symptom severity were compared by t test analysis. RESULTS: Forty
      percent of patients reported a psychotic symptom or symptoms in the preceding 6
      months. These symptoms featured auditory hallucinations in all but 1 case. The
      psychotic symptoms typically reflected combat-themes and guilt, were nonbizarre,
      and were not usually associated with formal thought disorder or flat or
      inappropriate affect. Psychotic symptoms were significantly associated with
      current major depression (p < .02), but not with alcohol or drug abuse or with
      self-rated PTSD and dissociation severity. Psychotic symptoms and current major
      depression were more common in minority (black and Hispanic) than white veterans
      (p < .002). CONCLUSION: Psychotic symptoms can be a feature of combat-related
      PTSD and appear to be associated with major depression. The association with
      minority status may be a function of comorbidity.

PMID- 10074875
TI  - Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual
      dysfunction in 4 patients.
AB  - OBJECTIVE: To evaluate the effect of sildenafil on iatrogenic serotonergic
      antidepressant-induced sexual dysfunction. METHOD: Four outpatients (2 men, 2
      women) who developed sexual dysfunction (erectile impotence, anorgasmia) during
      treatment with a serotonin reuptake inhibitor antidepressant for psychiatric
      disorder were selected. Each subject was initially prescribed sildenafil 50 mg to
      be taken approximately 1 hour before sexual activity. The dose was increased to
      100 mg for a partial or failed response. RESULTS: Four cases are detailed in case
      report fashion. All 4 had rapid reversal of their sexual dysfunction, usually
      with the first dose. Reversal equates to 1 successful use of sildenafil in each
      of 2 patients and 3 uses in 2 patients. CONCLUSION: Sildenafil may be an
      effective treatment for serotonergic antidepressant-induced sexual dysfunction
      and deserves further evaluation in randomized placebo-controlled studies.

PMID- 10074876
TI  - Effects of gender and age on plasma levels of clozapine and its metabolites:
      analyzed by critical statistics.
AB  - BACKGROUND: Previous reports concerning the effects of gender and age on steady
      state plasma concentrations of clozapine and its major metabolites, norclozapine
      and clozapine-N-oxide, have been controversial. Since the frequency distribution
      of the plasma levels is asymmetrical and skewed to the right, the statistical
      methods (such as analysis of variance and regression analysis) used earlier are
      actually inappropriate for analyzing the effects of the variables on the
      concentrations and might contribute to the inconsistent results. The goal of the
      present study, with befitting statistics, is to measure the potential effect of
      dose, gender, age, and body weight on plasma levels of clozapine and its 2 major
      metabolites. METHOD: We retrospectively analyzed data from a therapeutic drug
      monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N
      oxide levels that was conducted in a large group of Chinese schizophrenic
      inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily
      doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of
      379.5 +/- 142.2 mg. Plasma concentrations had been measured using high
      performance liquid chromatography with ultraviolet detection. Multiple linear
      regression was adopted to quantify the effects of various factors on the plasma
      levels. The natural logarithm of the plasma level was used as the dependent
      variable to overcome the skewness problem. RESULTS: After adjusting the effects
      of gender, age, and body weight by multiple linear regression, each 1-mg
      increment in the daily dose could raise the clozapine level by 0.31%,
      norclozapine by 0.27%, and clozapine-N-oxide by 0.16%. Female patients had 34.9%
      higher clozapine levels and 36.3% higher norclozapine, with other variables being
      controlled. No sex differences were demonstrated for clozapine-N-oxide levels.
      Each 1-year increment in age would elevate the clozapine level by 1.1%,
      norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not
      influence the levels of these compounds. CONCLUSION: The present results suggest
      that women possess higher plasma levels (about one third higher) of clozapine and
      norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age
      elevated clozapine and either metabolite's levels by about 1%. Furthermore, every
      1-mg increase in the daily dose raised clozapine and norclozapine concentrations
      by approximately 0.3%. These findings could assist clinicians in optimizing
      clozapine dosing strategies.

PMID- 10074877
TI  - The efficacy and safety of clozapine versus chlorpromazine in geriatric
      schizophrenia.
AB  - BACKGROUND: There has been an absence of controlled studies focusing specifically
      on neuroleptic treatment in the elderly schizophrenic population. Therefore, we
      conducted a 12-week double-blind comparison study to assess the efficacy and
      tolerability of clozapine and chlorpromazine in a group of elderly inpatients
      with chronic schizophrenia. METHOD: Forty-two elderly DSM-IV schizophrenic
      veterans were randomly assigned to clozapine or chlorpromazine and assessed for
      efficacy at baseline and at termination with the Positive and Negative Syndrome
      Scale (PANSS) and the Clinical Global Impressions scale (CGI). Side effects were
      also monitored. Medications were titrated, on the basis of clinical response and
      side effects, to a maximum dose of 300 mg/day of clozapine or 600 mg/day of
      chlorpromazine. RESULTS: The results suggest that both the chlorpromazine and
      clozapine groups improved their PANSS scores at termination compared with
      baseline, but the difference between the 2 groups was not statistically
      significant. The mean CGI scores reflecting severity of illness also demonstrated
      improvement in both groups over time. Both groups had similar incidences of side
      effects. One patient in each group had a life-threatening side effect. More
      patients taking clozapine had tachycardia and weight gain, while more
      chlorpromazine patients noted sedation. CONCLUSION: We concluded that both
      clozapine and chlorpromazine are effective treatments for psychosis and
      behavioral disturbances in geriatric schizophrenia. Both agents had similar
      incidences of side effects. With careful monitoring and titration of dosage, both
      clozapine and chlorpromazine were fairly well tolerated in this population.

PMID- 10074878
TI  - Mirtazapine augmentation in the treatment of refractory depression.
AB  - BACKGROUND: Pharmacotherapeutic strategies that target specific actions at
      multiple neuronal receptors or cellular components may offer a superior approach
      for treatment of refractory depression. Mirtazapine is a novel antidepressant
      which has a mechanism that involves the enhancement of noradrenergic and
      serotonergic neurotransmission via blockade of alpha2-adrenergic autoreceptors
      and heteroreceptors without activity at the serotonin transporter. Mirtazapine is
      thus a compelling candidate for augmentation treatment in patients who fail to
      achieve adequate response with other antidepressant medications. METHOD: Twenty
      patients with DSM-IV major depression or dysthmia who had persistent depressive
      syndromes despite at least 4 weeks of standard antidepressant pharmacotherapy
      were given augmentation with mirtazapine (15 to 30 mg p.o. q.h.s.) on an open
      label basis. Clinical assessments of status at baseline, 2 weeks, and 4 weeks
      were used to rate response. RESULTS: Forty-five percent (N = 9) of the sample
      were responders at 2 weeks. At the 4 week follow-up, 55% (N = 11) were
      responders, 30% (N = 6) were nonresponders, and 15% (N = 3) had discontinued
      treatment owing to side effects. Common side effects included weight gain and
      sedation. CONCLUSION: These data suggest that the addition of mirtazapine may be
      beneficial for patients who have refractory depression, but side effects are
      prominent at the doses we used. Controlled trials to further evaluate the
      efficacy and safety of mirtazapine augmentation are needed.

PMID- 10074879
TI  - Safety and feasibility of repetitive transcranial magnetic stimulation in the
      treatment of anxious depression in pregnancy: a case report.
AB  - BACKGROUND: The proper treatment of mood disorders occurring during pregnancy is
      a major therapeutic problem since no antidepressant medications have been
      established as safe for the developing fetus. Several double-blind placebo
      controlled studies have explored the efficacy of repetitive transcranial magnetic
      stimulation (rTMS) in depression. CASE: We report the case of a 36-year-old woman
      in her second trimester of pregnancy, whose depression (DSM-IV) and anxiety were
      successfully treated with rTMS. Further studies of rTMS in depressed pregnant
      women appear warranted.

PMID- 10074880
TI  - ECT-induced premature labor: a case report.

PMID- 10074881
TI  - Capitation.

PMID- 10074882
TI  - Risperidone augmentation of paroxetine in a case of severe, treatment-refractory
      obsessive-compulsive disorder without comorbid psychopathology.

PMID- 10074883
TI  - Donepezil overdose.

PMID- 10074884
TI  - Gender-related clinical differences in older patients with schizophrenia.
AB  - BACKGROUND: Gender differences in the clinical presentation of young patients
      with schizophrenia have been well-documented, yet few studies have investigated
      gender-related clinical differences in older patients. Furthermore, the symptoms
      of late-onset schizophrenia have been described, but the interaction between
      gender and age at onset has not been examined. METHOD: In an older (46-85 years
      of age) outpatient sample, we assessed clinical characteristics of women and men
      with early-onset schizophrenia (N = 90) and late-onset schizophrenia (N = 34).
      Subjects did not differ with respect to age, education, ethnicity, severity of
      depression, daily neuroleptic dosage, subtype of schizophrenia, total score on
      the Mini-Mental State Examination, or severity of overall psychopathology.
      Diagnosis was made using the Structured Clinical Interview for the DSM-III-R or
      DSM-IV. RESULTS: A significantly greater proportion of women had late-onset
      schizophrenia (41% vs. 20%), and women overall had more severe positive psychotic
      symptoms. Although there was no overall gender difference in severity of negative
      psychotic symptoms, women with late onset had significantly less severe negative
      symptoms than men with early onset, men with late onset, and women with early
      onset. Furthermore, age at onset of schizophrenia was inversely correlated with
      severity of negative symptoms for women, but not for men. These results indicate
      that women overall may develop more severe positive symptoms than men, and that
      when women develop schizophrenia after age 45, they may suffer less severe
      negative symptoms than men or than women with earlier onset. Our results suggest
      that some of the clinical differences between late-onset and early-onset
      schizophrenia may relate to gender effects, and that there may be inherent
      differences in the clinical presentation of schizophrenia that are related to
      gender and gender by age at onset interactions. CONCLUSION: These differences may
      reflect the influence of sex hormones and menopause on the clinical presentation
      of schizophrenia or the possible existence of an "estrogen-related" form of
      schizophrenia in women with late-onset schizophrenia.

PMID- 10074885
TI  - Procedure for the quantitation of Gadd45 expression levels in clonal
      hematopoietic progenitor cells by competitive polymerase chain reaction.
AB  - OBJECTIVE: The growth arrest and DNA damage-inducible (gadd) genes represent a
      family of stress-inducible genes that are coordinately regulated at
      transcriptional level. Gadd45, in particular, has been linked to a p53-dependent
      inducible network required for regulated transition from G1 to S phase of cell
      cycle following genotoxic insult and growth arrest treatments and has seemingly a
      pivotal role in DNA repair. DESIGN AND METHODS: Here we show that competitive
      polymerase chain reaction (PCR) is an adequate method to quantitate gadd45
      expression levels in hematopoietic progenitor cell line 32D, whose constitutive
      gene expression is very low. RESULTS: The sensitivity and reproducibility of our
      strategy support its usefulness for clinical purposes, to assess the DNA repair
      capacity of highly purified early myeloid progenitors, whose failure may be
      responsible for either short-term chemotherapy side effects (bone marrow
      hypoplasia and peripheral blood cytopenia) or long-term consequences of
      antiblastic drugs (leukemia and myelodysplasia).

PMID- 10074886
TI  - Analysis of nitrite and nitrate in biological fluids by capillary
      electrophoresis.
AB  - OBJECTIVES: We report a method for determining nitrite and nitrate in biological
      fluids by capillary electrophoresis. METHODS: A Waters capillary electrophoresis
      system was used with a filter for detection at 214 nm. After dilution with
      distilled water, the sample was loaded hydrostatically onto a 60 cm x 100 microm
      capillary and electrophoresed at 15 kV in 15 mmol/L sulfate buffer, pH 8.0,
      containing 2.5% electroosmotic flow modifier. RESULTS: The retention times for
      nitrite and nitrate were 3.9 +/- 0.8 and 4.0 +/- 0.8 min, respectively. The
      detection limit was 10 micromol/L for serum nitrate. The recovery was 93-115% for
      nitrite and 92-106% for nitrate. The within-day and between-day coefficients of
      variation were lower than 3.3% and 5.0%, respectively, for two pools with normal
      (28 micromol/L) and high (87 micromol/L) nitrate concentration. A comparison with
      the nitrate reductase method gave a correlation coefficient of 0.982. CONCLUSION:
      Capillary electrophoresis provides many advantages, namely low cost, small sample
      and buffer requirements, rapidity, which makes its use particularly suitable for
      clinical laboratories.

PMID- 10074887
TI  - Development and evaluation of a direct sandwich enzyme-linked immunosorbent assay
      for the quantification of lipoprotein lipase mass in human plasma.
AB  - OBJECTIVE: The purpose of this study was to develop and evaluate a direct
      sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the
      lipoprotein lipase (LPL) immunoreactive mass in human plasma using monoclonal
      antibodies (MAbs) directed against LPL purified from human postheparin plasma
      (PHP) [corrected]. METHODS AND RESULTS: The direct sandwich-ELISA was performed
      using a combination of two distinct types of MAbs that recognize different
      epitopes on the LPL molecule. The immunoreactive mass of human LPL was
      specifically measured using a horseradish peroxidase-labeled anti-human LPL MAb
      [1(1)D2B2] as an enzyme-linked MAb, and an anti-human LPL MAb [2(10)F8F9] coated
      on a polystyrene microtiter plate as a solid-phase MAb. Purified human PHP-LPL
      was used as a standard material. The detection range of the sandwich-ELISA was
      3.6-460 ng of LPL protein per mL of plasma. The intra- and interassay
      coefficients of variation were less than 5.9% and 3.3%, respectively. The
      validity of this method was additionally assured by the recovery test, which
      resulted in the variation only between 97.5% and 105.1%, and also by the
      interference test, which resulted in noninterference of LPL assay with a high
      concentration of triglyceride, hemoglobin, bilirubin, uric acid, or creatinine.
      To assess the reliability of the LPL mass values obtained with the direct
      sandwich-ELISA, they were compared with LPL mass values determined by the one
      step sandwich-EIA (MARKIT-F LPL EIA kit) previously established by us. This
      comparison showed a highly significant correlation (r = +0.990) between the two
      sets of values. The LPL mass concentrations in PHP from 33 healthy subjects were
      267 +/- 53 and 257 +/- 59 ng/mL (mean +/- SD), respectively. CONCLUSION: The
      present direct sandwich-ELISA is useful for rapidly identifying certain
      abnormalities of LPL in PHP samples from patients with hypertriglyceridemia
      [corrected].

PMID- 10074888
TI  - Reference values of urinary excretion of cystine and dibasic aminoacids:
      classification of patients with cystinuria in the Valencian Community, Spain.
AB  - OBJECTIVE: Cystinuria is an autosomal-recessive disorder of the kidneys and small
      intestine affecting a luminal transport mechanism shared by cystine, ornithine,
      arginine, and lysine. Three different types of cystinuria can be distinguished
      according to the excretion of these amino acids in urine samples. We propose
      cutoff values from our population as references and we present a classification
      of cystinuric patients using quantitative amino acid chromatography in first
      morning urine samples. DESIGN AND METHODS: A random sample of forty healthy
      subjects belonging to general population of the Valencian Community were selected
      as control subjects. Cystine, lysine, arginine, and ornithine were quantified by
      reverse-phase HPLC. Seventy-two subjects, diagnosed previously as cystinuric by
      the cyanide-nitroprusside test were classified. Probands excreting more than
      113.12 micromol cystine per mmol of creatinine (i.e., 1,000 micromol cystine per
      gram of creatinine) were classified as homozygotes. Parents of homozygotes in
      whom excretion of amino acids were normal were classified as heterozygotes type
      I. Those probands showing the excretion of at least one amino acid and the sum of
      urinary cystine plus the basic amino acids higher than the corresponding
      references ranges in our population were classified as heterozygotes type II or
      type III (heterozygotes non-type 1). RESULTS: We identified 24 homozygotes, 39
      non-type I heterozygotes and 3 type I heterozygotes. The remaining 6 probands
      could not be classified. Means for cystine, lysine, arginine ornithine and their
      sum in homozygotes and heterozygotes non-type I were significantly (p < 0.001) in
      excess of the respective reference ranges. Moreover, means values in homozygotes
      were statistically different (p < 0.001) from heterozygotes non-type I.
      CONCLUSION: Urinary excretion of cystine per mmol creatinine allow us to
      distinguish heterozygotes from homozygotes. However, the best discriminator to
      distinguish non-type I heterozygotes from normal population might be the
      excretion of lysine per mmol creatinine. Additional studies including
      characterization of appropriate haplotypes should be carried out for a more
      precise identification of types of cystinuria.

PMID- 10074889
TI  - Prostate-specific antigen ratio correlates with aggressiveness of histology
      grades of prostate cancer.
AB  - OBJECTIVES: To compare prostate-specific antigen (PSA) ratio to total PSA (tPSA)
      assay for prostate cancer diagnosis and to study the correlation of PSA ratio
      with histology grade of prostate cancer. METHODS: Among 334 selected cases, 136
      had benign prostate diseases and 198 had prostate cancer. All cases underwent
      transrectal ultrasound (TRUS) and tissue biopsies within 6 months of their tPSA
      measurements. All of the tPSA levels taken were between 2 and 20 microg/L. The
      serum tPSA and free PSA were assayed using the Abbott AxSYM immunoassay system
      (Abbott Laboratories; Abbott Park, IL, USA). The PSA ratios of patients with
      prostate cancer were compared to those with benign prostate diseases (BPD) using
      the Student's t test. Correlation between the histology grades and PSA ratios was
      calculated by Pearson test. Receiver operating characteristic (ROC) curves were
      generated from sensitivities and specificity of various PSA ratios and tPSA
      levels. RESULTS: We found an inverse correlation between PSA ratios and
      aggressiveness of histology grades (r = -0.995, p < 0.01). The higher the
      histology grade, the lower the PSA ratio tended to be, and the more sensitive and
      specific the PSA ratio was in the diagnosis of prostate cancer. No correlation
      was found between histology grades and tPSA levels. A PSA ratio of 0.25 diagnosed
      93% of patients with Gleason score greater than 7 and 83% of all prostate cancer
      patients. It would have reduced unnecessary biopsies by 23% compared to the tPSA
      level of 4 microg/L. Sensitivity of PSA ratios was higher and specificity was
      lower in high tPSA level group than they were in low tPSA level group.
      CONCLUSIONS: PSA ratio inversely correlates to aggressiveness of prostate cancer
      and has a potential to predict histology grade of prostate cancer. PSA ratio
      improves sensitivity and specificity for prostate cancer diagnosis compared to
      tPSA assay.

PMID- 10074890
TI  - Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid
      and their potential utility for cyst type classification.
AB  - OBJECTIVE: To quantify pepsinogen C (PEPC) and prostaglandin D synthase (PGDS) in
      breast cyst fluid and examine if these two parameters can be used for breast cyst
      type classification. DESIGN AND METHODS: We quantified PEPC and PGDS in 92 and 50
      breast cyst fluids, respectively, using previously established immunofluorometric
      procedures. We then examined if the levels of PEPC or PGDS correlate with the
      type of cyst or with other clinicopathological variables. RESULTS: Quantitative
      analysis of the breast cyst fluids indicated that PEPC is present in all cyst
      fluids at various concentrations ranging from 3 to 31,000 ng/mL. PGDS positivity
      was confined to 30% of the cyst fluids. PEPC and PGDS levels were correlated with
      the breast cyst fluid cation ratio and were associated with the type of the cyst.
      Increased PEPC levels in breast cyst fluids were significantly correlated with a
      > or = 1.5 K+/Na+ ratio and were associated with the secretory/apocrine type of
      cyst (Type I) (p = 0.011). Immunoreactive PGDS levels were highly correlated with
      a low cation ratio and were associated with the transudative/flattened type of
      breast cyst (Type II) (p = 0.0003). A weak association was observed between PEPC
      levels in breast cyst fluid and menopausal status (p = 0.093). No significant
      associations were observed for either PEPC or PGDS concentration in breast cyst
      fluid and number of cysts, recurrence of the disease, family history of breast
      cancer, number of children, abortion, and breast feeding. CONCLUSIONS:
      Quantification of PEPC and PGDS in breast cyst fluid may be useful in the
      subclassification of cyst type in patients with gross cystic disease.

PMID- 10074891
TI  - Bcl-2 gene rearrangements and apoptosis rates in patients with non-Hodgkin's
      lymphoma during chemotherapy.
AB  - OBJECTIVES: Overexpression of the bcl-2 gene as a result of the t(14,18)
      translocation leads to neoplastic transformation by suppressing apoptosis.
      However, apoptotic cell death in response to chemotherapy has not been
      investigated. This study was planned with the aim to investigate the association
      between bcl-2 gene rearrangements and apoptotic changes during chemotherapy in
      patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: Lymphocytes from 33
      patients were collected before and during chemotherapy. Bcl-2 gene rearrangements
      were investigated by PCR. Apoptotic cell death was analyzed by enzyme
      immunoassay. RESULTS: In 24 cases, mbr gene rearrangements were detected.
      Apoptosis was successfully induced by chemotherapy in 48% of patients. Two
      characteristic, clearly distinguishable apoptotic response patterns with
      transient peaks either following the first or the third course were observed. It
      was found that apoptosis rates measured after the first course exactly reflect
      the final response. No correlation was found between bcl-2 gene rearrangements
      and apoptosis. CONCLUSIONS: Apoptotic cell death rates show transient changes
      during chemotherapy. Because the midterm response can be misleading, the
      apoptotic response should be evaluated following the first course of
      chemotherapy.

PMID- 10074892
TI  - Effect of combined immunosuppressive drug therapy on small intestinal nutrient
      transport in the rat.
AB  - OBJECTIVE: Prevention of rejection and preservation of graft function remain as
      obstacles to clinical small intestinal transplantation (SIT). This study
      evaluated the effects of combined immunosuppressive agents (FK506, Rapamycin, and
      Mycophenolate Mofetil) on intestinal function and animal well being. METHODS:
      Screening for additive toxicity was done in experiment one (D1, n = 10); doses
      were: FK506 0.3 mg/kg/d, Rapamycin 2 mg/kg/d, and Mycophenolate Mofetil 20
      mg/kg/d, orally once daily. Control animals (C1, n = 10) received equivalent
      vehicle. In the second phase of the experiment, the effect of an additional
      parenteral treatment phase was investigated, with drug treated animals (D2, n =
      6) received FK506 0.3 mg/kg, Rapamycin 1 mg/kg, and Mycophenolate Mofetil 10
      mg/kg sq q12h for 1 week followed by FK506 3 mg/kg, Rapamycin 1 mg/kg, and
      Mycophenolate Mofetil 10 mg/kg p.o. q12h for 4 weeks. Control animals (C2, n = 6)
      received equivalent vehicle. Parameters followed were weight gain, nutrient
      absorption, drug levels and nutrient transport in vitro. RESULTS: Controls grew
      normally, while weight gain was significantly reduced in drug treated animals:
      This was paralleled by a reduction in dietary fat absorption. Drug levels were
      low to therapeutic for all drugs in both experiments; FK506 appeared to affect
      Rapamycin and Mycophenolate Mofetil metabolism, increasing levels of both as
      FK506 doses increased. Nutrient transport was either not effected (D1) or
      increased (D2). CONCLUSIONS: We conclude that low dose combination
      immunosuppressive therapy inhibits weight gain, without affecting absorption of
      dietary energy, or adversely affecting glucose transport. We postulate a systemic
      metabolic cause, which requires additional investigation at the cellular level;
      additional studies are also required to determine if the additive
      immunosuppression outweigh the side effects for SIT.

PMID- 10074893
TI  - Clinical validation of the Helikit: a 13C urea breath test used for the diagnosis
      of Helicobacter pylori infection.
AB  - OBJECTIVE: To assess the clinical performance of the Helikit, a 13C urea breath
      test, in the diagnosis of Helicobacter pylori infection. METHODS: A total of 205
      participants were assessed in Canada and Korea for H. pylori infection status by
      endoscopy, or a combination of IgG ELISA and CLO test, as well as by the Helikit.
      The Helikit contains 75 mg of 13C urea as well as citric acid, flavor enhancers
      and stabilizers in a single plastic cup. The powder is dissolved in 75 mL of
      water for oral administration. No extra mixing or dilution steps are required.
      RESULTS: Using the biopsy-derived data as the gold standard the Helikit displayed
      a clinical sensitivity of 93.5% (95% confidence interval 88.5 to 98.5%) and a
      clinical specificity of 97.3% (94.3 to 100%). An overall diagnostic efficiency of
      95.6% (92.8 to 98.4%) was obtained. No statistically significant difference in
      the performance characteristics was found between Korea and Canada. No
      significant adverse events were noted. CONCLUSIONS: The Helikit offers an easy,
      safe and accurate approach to the diagnosis of H. pylori infection.

PMID- 10074894
TI  - Increased plasma levels of homocysteine and other thiol compounds in rheumatoid
      arthritis women.
AB  - OBJECTIVES: Since moderate hyperhomocysteinemia is an independent risk factor for
      vascular disease and physiological thiol compounds mediate Cu2+- and Fe3+
      dependent low-density lipoprotein (LDL) oxidation, we have studied the total
      plasma concentrations of thiol compounds including methionine as precursor of
      homocysteine in rheumatoid arthritis patients, in which the high mortality found
      is associated with cardiovascular disease. DESIGN AND METHODS: Thirty-eight women
      with rheumatoid arthritis and 25 age-matched control women were studied. Plasma
      was used to measure thiol compounds and amino acids by HPLC. RESULTS: Rheumatoid
      arthritis patients showed significantly higher levels than healthy controls of
      total plasma homocysteine (17.3 +/- 7.8 vs. 7.6 +/- 1.9; p <0.001), cysteine (293
      +/- 61 vs. 201 +/- 45; p < 0.001), cysteinglycine (32.7 +/- 8.3 vs. 22.3 +/- 4.7;
      p < 0.001) and methionine (25 +/- 9 vs. 18 +/- 3; p < 0.01), whereas total
      glutathione levels were not increased (4.7 +/- 2.0 vs. 4.1 +/- 1.6). CONCLUSIONS:
      The increased levels of thiol compounds found in rheumatoid. arthritis patients
      may be implicated in the increased incidence of cardiovascular disease found in
      these patients by means of the toxic effect of homocysteine on endothelium and
      the increased susceptibility of LDL to oxidation by increased plasma amounts of
      thiol compounds such as cysteine.

PMID- 10074895
TI  - Serum leptin as an additional possible pathogenic factor in polycystic ovary
      syndrome.
AB  - OBJECTIVES: Recent data raised the possibility that high leptin levels may
      contribute to infertility in some women with PCOS. DESIGN AND METHODS: To assess
      changes in leptin levels and its relationship to some hormonal changes (insulin,
      testosterone, SHBG, FSH, LH, and prolactin) associated with PCOS in obese (n =
      27) and nonobese (n = 18) patients when compared to obese and nonobese normal
      controls (n = 20). RESULTS: Leptin concentration were significantly higher in
      PCOS than in controls, p < 0.05, with 81% sensitivity and 50% specificity.
      Whereas, high serum insulin levels were found in obese and nonobese women with
      PCOS, high serum leptin, FAI together with reduced SHBG were found in obese
      rather than nonobese PCOS women. Moreover, hyperleptinemia in PCOS women was not
      correlated to hyperinsulinemia (r = -0.13 and -0.4 in obese and nonobese PCOS
      women, respectively). In the patient's group correlation analysis between fasting
      serum leptin and different studied variables showed some correlation with body
      mass index (BMI) only (r = 0.413) suggesting that high leptin levels could be a
      characteristic of the obese PCOS. However, multiregression analysis showed that
      together with testosterone, leptin can successfully predict the presence or
      absence of PCOS. CONCLUSION: The potential significance of leptin for the
      pathophysiology of PCOS will await direct studies of the effects of exogenous
      leptin and/or its inhibitors on the reproductive axis of women, including those
      with PCOS.

PMID- 10074896
TI  - Pediatric reference ranges for creatine kinase, CKMB, Troponin I, iron, and
      cortisol.
AB  - OBJECTIVES: To determine the pediatric reference ranges for iron, cortisol, CK,
      CKMB, and troponin I. METHODS: Iron and CK were measured on the Vitros analyzer
      (Johnson and Johnson) while CKMB, troponin I, and cortisol were measured on the
      Immuno I (Bayer Corp.). Pediatric reference ranges were determined on
      hospitalized patients using the Hoffmann approach. RESULTS: Pediatric reference
      ranges were obtained for iron (AM and PM) and cortisol (AM and PM). Ranges were
      also obtained for CKMB, troponin I, and total CK. CONCLUSION: This work
      represents an expansion in our knowledge base on pediatric reference ranges. For
      iron, the 97.5th percentiles were significantly higher in the PM than in the AM.
      The diurnal fluctuation in 97.5th percentiles for cortisol was only 10-20%.
      Pediatric reference ranges for CKMB were not previously available and are
      important especially in the first year of life. The elevated Troponin I is found
      in the first year of life also represents new data.

PMID- 10074897
TI  - Lack of association between mitochondrial DNA mutation np3243 and maternally
      inherited diabetes mellitus.

PMID- 10074898
TI  - A necessary adjustment of protocol for use of DPC coat-a-count total testosterone
      assay with saliva.

PMID- 10074899
TI  - Stability of human plasma leptin concentrations within 36 hours following
      specimen collection.

PMID- 10074900
TI  - 5'-Ectonucleotidase in chronic lymphocytic leukemia.

PMID- 10074901
TI  - Malignant transformation of p53-deficient astrocytes is modulated by
      environmental cues in vitro.
AB  - The early incidence of p53 mutation in astrocytomas suggests that it plays an
      important role in astrocyte transformation. Astrocytes isolated from homozygous
      p53 knockout mice grow rapidly, lack contact inhibition, and are immortal. Here
      we tested whether the loss of p53 is sufficient for progression to tumorigenicity
      of astrocytes. We grew primary astrocytes under three conditions for over 120
      population doublings and assessed their antigenic phenotype, chromosome number,
      and expression of glioma-associated genes as well as their ability to form
      colonies in soft agarose and tumors s.c. and intracranially in nude mice. Under
      two conditions (10% FCS and 0.5% FCS plus 20 ng/ml EGF), cells acquired the
      ability to form colonies in soft agarose and tumors in nude mice, and this was
      accompanied by the expression of genes, including epidermal growth factor
      receptor, platelet-derived growth factor receptor alpha and beta, protein kinase
      Cdelta, and vascular endothelial growth factor, which are known to be aberrantly
      regulated in human astrocytomas. Under the third condition (0.5% FCS plus 10
      ng/ml basic fibroblast growth factor), astrocytes gained the ability to form
      colonies in soft agarose and had abnormal chromosome numbers similar to cells in
      the first two conditions but did not form tumors in nude mice or overexpress
      glioma-associated genes. These data provide experimental evidence for the idea
      that the malignant progression initiated by the loss of p53 may be subject to
      modulation by extracellular environmental influences.

PMID- 10074902
TI  - Analysis of the degradation function of Mdm2.
AB  - Degradation of the p53 tumor suppressor protein has been shown to be regulated by
      Mdm2. In this study, we identify regions of Mdm2 that are not required for p53
      binding but are essential for degradation. Mdm2 mutants lacking these regions
      function in a dominant negative fashion, stabilizing endogenous p53 in cells by
      interfering with the degradative function of the endogenous Mdm2. p53 protein
      stabilized in this way does not strongly enhance the expression of
      p21(Waf1/Cip1), the product of a p53-responsive gene, supporting the model in
      which binding of Mdm2 to the NH2-terminal domain of p53 inhibits interaction with
      other components of the basal transcriptional machinery. Interestingly, COOH
      terminal truncations of Mdm2 that retain p53 binding but fail to mediate its
      degradation are also stabilized themselves. Because Mdm2, like p53, is normally
      an unstable protein that is degraded through the proteasome, this result suggests
      a direct link between the regulation of Mdm2 and p53 stability.

PMID- 10074903
TI  - Retardation of cell proliferation after expression of p202 accompanies an
      increase in p21(WAF1/CIP1).
AB  - p202 is an IFN-inducible, primarily nuclear, phosphoprotein (52-kDa) whose
      constitutive overexpression in transfected cells inhibits colony formation. To
      investigate the molecular mechanism(s) by which expression of p202 protein
      impairs colony formation, we established stable cell lines that inducibly express
      p202. Using this cell model, we demonstrate that the induced expression of p202
      in asynchronous cultures of these cells was accompanied by: (a) an increase in
      steady-state levels of p21(WAF1/CIP1/SDI1) (p21) mRNA and protein; (b) a decrease
      in Cdk2 protein kinase activity; and (c) an increase in the functional form of
      retinoblastoma protein (pRb). Transient transfection of a p202-encoding plasmid
      in Saos-2 cells, which do not harbor a wild-type p53 protein, resulted in an
      increase in p21 protein, which indicated that p202 could regulate expression of
      p21 protein independent of p53 protein. Moreover, we demonstrate that expression
      of p202 in these cells increased cell doubling time without accumulation of cells
      in a particular phase of the cell cycle. Taken together, these results are
      consistent with the possibility that p202 protein contributes to the cell growth
      retardation activity of the IFNs, at least in part, by modulating p21 protein
      levels.

PMID- 10074904
TI  - Concordant induction of cyclin E and p21cip1 in differentiated keratinocytes by
      the human papillomavirus E7 protein inhibits cellular and viral DNA synthesis.
AB  - Productive infections by human papillomaviruses (HPVs) occur only in
      differentiated keratinocytes in squamous epithelia in which the HPV E7 protein
      reactivates the host DNA replication machinery to support viral DNA replication.
      In a fraction of the differentiated keratinocytes, E7 also posttranscriptionally
      induces p21Cip1, which is distributed in a mutually exclusive manner with
      unscheduled cellular DNA synthesis. In this study, double immunofluorescence
      labeling unexpectedly revealed that E7 caused a concordant accumulation of both
      cyclin E and p21Cip1 to high levels in patient papillomas and in organotypic
      cultures of primary human keratinocytes. The induction of cyclin E is mutually
      exclusive with unscheduled cellular DNA synthesis or abundant viral DNA. These
      novel virus-host interactions in differentiated keratinocytes are in contrast to
      previous observations made in submerged proliferating cultures, in which HPV E7
      induces cyclin E and overcomes p21Cip1 inhibition of S-phase entry. We propose
      that an appropriately timed induction of cyclin E/cyclin-dependent kinase 2 by
      HPV E7 in postmitotic cells enables S-phase reentry and HPV DNA amplification,
      whereas prematurely induced cyclin E stabilizes p21Cip1 protein, which then
      inhibits cyclin E/cyclin-dependent kinase 2. Consequently, cyclin E and p21Cip1
      both fail to turn over, and DNA synthesis does not occur.

PMID- 10074905
TI  - Cell cycle-dependent nuclear accumulation of the p94fer tyrosine kinase is
      regulated by its NH2 terminus and is affected by kinase domain integrity and ATP
      binding.
AB  - p94fer and p51ferT are two tyrosine kinases that are encoded by differentially
      spliced transcripts of the FER locus in the mouse. The two tyrosine kinases share
      identical SH2 and kinase domains but differ in their NH2-terminal amino acid
      sequence. Unlike p94fer, the presence of which has been demonstrated in most
      mammalian cell lines analyzed, the expression of p51ferT is restricted to meiotic
      cells. Here, we show that the two related tyrosine kinases also differ in their
      subcellular localization profiles. Although p51ferT accumulates constitutively in
      the cell nucleus, p94fer is cytoplasmic in quiescent cells and enters the nucleus
      concomitantly with the onset of S phase. The nuclear translocation of the FER
      proteins is driven by a nuclear localization signal (NLS), which is located
      within the kinase domain of these enzymes. The functioning of that NLS depends on
      the integrity of the kinase domain but was not affected by inactivation of the
      kinase activity. The NH2 terminus of p94fer dictated the cell cycle-dependent
      functioning of the NLS of FER kinase. This process was governed by coiled-coil
      forming sequences that are present in the NH2 terminus of the kinase. The
      regulatory effect of the p94fer NH2-terminal sequences was not affected by kinase
      activity but was perturbed by mutations in the kinase domain ATP binding site.
      Ectopic expression of the constitutively nuclear p51ferT in CHO cells interfered
      with S-phase progression in these cells. This was not seen in p94fer
      overexpressing cells. The FER tyrosine kinases seem, thus, to be regulated by
      novel mechanisms that direct their different subcellular distribution profiles
      and may, consequently, control their cellular functioning.

PMID- 10074906
TI  - Met-HGF/SF mediates growth arrest and differentiation in T47D breast cancer
      cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent growth factor
      that exerts mitogenic, motogenic, and morphogenic effects. To elucidate the
      cellular mechanisms underlying the pluripotent function of this growth factor,
      T47D human breast cancer cells were transfected with human hgf/sf. The hgf/sf
      positive clones exhibited different levels of biologically functional HGF/SF
      expression and up-regulation of endogenous Met (HGF/SF receptor) expression. In
      addition, a constitutive phosphorylation of the receptor on tyrosine residues was
      detected, establishing a Met-HGF/SF autocrine loop. The autocrine activation of
      Met caused marked inhibition in cell growth accompanied by cell accumulation at
      G0/G1. These cells underwent terminal cell differentiation as determined by
      morphological changes, synthesis of milk proteins such as beta-casein and alpha
      lactalbumin, and production of lipid vesicles. Our results demonstrate that Met
      HGF/SF, an oncogenic signal transduction pathway, is capable of inducing growth
      arrest and differentiation in certain breast cancer cells and, thus, may have
      potential as therapeutic and/or prognostic tools in breast cancer treatment.

PMID- 10074907
TI  - Synthetic inhibitors of thrombin and factor Xa: from bench to bedside.

PMID- 10074908
TI  - Effect on platelet FXIII and partial characterization of Lonomin V, a proteolytic
      enzyme from Lonomia achelous caterpillars.
AB  - Contact with Lonomia achelous caterpillars venom induces a severe bleeding
      syndrome in humans. A constant finding in all reported cases is a marked decrease
      of blood coagulation factor XIII (FXIII), which has been attributed to the
      presence of a proteolytic enzyme, isolated and named Lonomin V, in the hemolymph
      and hair secretion. In this study, the effect of Lonomin V on transglutaminase
      activity from human plasma, rabbit plasma, and platelet FXIII was analyzed. The
      decrease of activity was more pronounced in platelet (A2) when compared with
      rabbit plasma (AB) and human plasma FXIII (A2B2). This finding might be explained
      by the differences in FXIII molecular structure. In addition, platelet FXIII
      molecule was degraded by Lonomin to several fragments of low molecular mass.
      Lonomin V was stable over a wide range of pH (6-8.5) and temperatures of -70
      degrees C, -20 degrees C and between 4 to 24 degrees C, with a progressive
      decrease at 37 degrees C and total inactivation at 60 degrees C after 2 hours
      incubation. Diisopropyl fluoro-phosphate, phenylmethylsulfonyl fluoride, tosyl-l
      lysine chloromethyl ketone, and iodoacetamide abolished the effect of Lonomin V
      on FXIII; in contrast dithiothreitol and EDTA-Na enhance the activity. We
      concluded that Lonomin V is a serine proteinase with a free Cys essential for the
      enzymatic activity. Due to its proteolytic activity on FXIII, with concomitant
      impairment of fibrin cross-linking, Lonomin V might be useful in association with
      thrombolytic drugs for preventing rethrombosis.

PMID- 10074909
TI  - Molecular expression of PSMA mRNA and protein in primary renal tumors.
AB  - Human prostate-specific membrane antigen (PSMA), a 100-kDa integral transmembrane
      glycoprotein, is considered to be a highly specific marker of the prostate gland,
      and has successfully been used as a marker of circulating prostatic epithelial
      cells. Extended PSMA homology has been demonstrated with a cDNA found in rat
      cerebral and renal tissues. In this study, we aimed to evaluate the expression of
      PSMA mRNA in a variety of human renal cancer tissues (n = 20) and cell lines (n =
      12). Using reverse transcriptase-polymerase chain reaction, DNA sequencing,
      blottings, and specific anti-PSMA labelling with CYT 351 antibody, we identified
      PSMA mRNA and protein in normal and in neoplastic renal tissue. The sequence of
      the polymerase-chain-reaction products is identical to that of PSMA cDNA derived
      from prostate tissue. Immunological staining with the CYT 351 reveals that PSMA
      is expressed mainly in tubular cells. Since PSMA does not appear to be restricted
      to prostatic tissue, this novel biomarker may prove useful in the staging of
      renal cancer and in the search for the hematogenous spread of renal cells.

PMID- 10074910
TI  - Expression of human telomerase subunits in ovarian malignant, borderline and
      benign tumors.
AB  - Telomerase activity is involved in the maintenance of telomere length and is
      thought to be required for cellular immortality and oncogenesis. Three major
      subunits composing telomerase, human telomerase RNA (hTR), telomerase-associated
      protein (TPI) and human telomerase catalytic subunit (hTERT), have been
      identified. However, their functions and the regulatory mechanisms by which
      telomerase is activated have not been fully determined. In the present study, a
      total of 35 epithelial ovarian cancers, 5 ovarian low potential malignancies
      (LPM), 11 ovarian benign cysts and 12 normal ovaries, as well as various cell
      lines derived from ovarian cancers, were examined for the expression of hTR, TPI
      mRNA and hTERT mRNA. Correlations of expression with telomerase activity were
      evaluated. Reverse transcription-polymerase chain reaction (RT-PCR) analysis
      revealed that hTR and TPI mRNA were expressed in more than 80% of ovarian
      cancers, LPM, ovarian cysts and even in normal ovaries. However, hTERT mRNA was
      observed only in ovarian cancers, most of which exhibited telomerase activity.
      Normal ovarian tissues, ovarian cysts and LPM, most of which had no telomerase
      activity, did not express hTERT. Five telomerase-positive ovarian cancer cell
      lines expressed each of the telomerase subunits, whereas 2 telomerase-negative
      normal primary fibroblast cell lines expressed TPI mRNA and hTR, but not hTERT
      mRNA. There was a significant correlation of telomerase activity with hTERT mRNA
      expression but not with TPI or hTR expression. Expression of hTERT is thus
      specific to cancer lesions and appears to be a rate-limiting determinant of the
      enzymatic activity of human telomerase. Up-regulation of hTERT may play a
      critically important role in the development of ovarian cancers.

PMID- 10074911
TI  - Angiogenesis vs. response after combined chemoradiotherapy of squamous cell head
      and neck cancer.
AB  - Oxygen/drug supply to cancer cells is an important factor defining response to
      radiotherapy and chemotherapy. Although tumor angiogenesis is considered an
      important prognostic marker, its role in the outcome of chemotherapy and
      radiotherapy is unknown. In the present study we examined the possible
      correlation of the degree of angiogenesis with response to cytotoxic therapy in
      locally advanced squamous cell head and neck cancer (HNC). Vascular grade (VG)
      was assessed immunohistochemically using the JC70 monoclonal antibody (MAb) in
      tumor specimens from 76 patients treated with platinum/5-fluorouracil (with or
      without methotrexate) induction chemotherapy (ICT) (n = 37) or concurrent
      chemoradiotherapy (CCRT) with cisplatin or carboplatin (n = 39). Seventeen of 76
      analyzed patients had an overall microvessel score of < 11 (VGI), 25/76 of 11-30
      (VG2), 16/76 of 31-50 (VG3) and 18/76 of > 50 (VG4). Complete response rate after
      ICT or after CCRT was higher in cases with an intermediate vascularization
      (VG2,3). Both local relapse-free and overall survival were significantly better
      in the VG2 group. Patients treated with CCRT had a better survival compared to
      those treated with ICT. This was mainly observed in VG1 tumors. Multivariate
      analysis showed that VG and treatment modality were independent prognostic
      factors for local relapse and survival. Intratumoral angiogenesis correlation
      with the cytotoxic therapy outcome is likely to follow a bell-shaped relation,
      the response being better in cases with an intermediate VG. This may be the
      consequence of 2 vasculature-dependent factors, i.e., the drug/oxygen
      availability and the ability of cancer cells to undergo rapid repopulation in
      optimally oxygenated conditions. Our pilot study stresses the importance of
      individualization of therapy according to VG.

PMID- 10074912
TI  - No excess risk of cervical carcinoma among women seropositive for both HPV16 and
      HPV6/11.
AB  - Human papillomavirus (HPV) types 16 and 18 are the major risk factors for
      cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We
      wanted to study the joint effect of simultaneous infections with the oncogenic
      and non-oncogenic HPV types on risk of subsequent development of cervical
      carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic
      serum banks between 1973 and 1994 was followed up by linkage to national cancer
      registries. We identified 182 prospective cases with invasive cervical carcinoma
      and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33
      seropositivity was used as a marker for the different HPV infections, and
      seropositivity for Chlamydia trachomatis and cotinine were used as markers for
      risk-taking sexual behavior and smoking respectively. The adjusted odds ratio
      (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16
      seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming
      multiplicative joint effect, the expected OR for seropositivity to both HPV6/11
      and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic
      interaction was statistically significant (p = 0.001) and present also under
      deterministic considerations of possible misclassification bias. Antagonistic
      interactions were also detected for combinations of HPV16 and HPV18 and of HPV16
      and HPV33. The results are in line with the concept that HPV-specific immunity
      protects against SCC and support primary prevention of SCC by vaccination against
      the HPVs.

PMID- 10074913
TI  - Quantification of BRCA1 protein in sporadic breast carcinoma with or without loss
      of heterozygosity of the BRCA1 gene.
AB  - In sporadic breast cancer, no mutations of the BRCA1 gene have been reported so
      far, whereas BRCA1 mRNA is markedly decreased in invasive breast cancer. To
      elucidate the contribution of the BRCA1 gene in sporadic breast cancer, we
      quantified the BRCA1 protein, using [125I] labeling of whole-cell proteins,
      lentil-lectin affinity chromatography, immunoprecipitation by anti-BRCA1
      antibodies (C-20, D-20, I-20 and K-18), purification of the immune complex by
      protein A affinity chromatography and chromato-focusing. As loss of 1 allele may
      lead to a decreased expression of the gene, 10 tumors were previously checked for
      loss of heterozygosity (LOH) of the BRCA1 gene, using 3 intragenic microsatellite
      markers. Our results indicated that the BRCA1 gene product was decreased in the 4
      tumors with LOH compared with matched normal breast tissues. Reduced amounts of
      BRCA1 protein were also detected in 3 of 6 tumors without LOH. Our quantitative
      method allowed us to demonstrate that the BRCA1 protein level was decreased in
      sporadic invasive breast carcinomas with or without LOH of the BRCA1 gene,
      implying multiple mechanisms of BRCA1 expression down-regulation in these tumors.
      Our data suggest that the amount of BRCA1 protein present may play an important
      role in human sporadic breast carcinoma.

PMID- 10074914
TI  - Estimates of the worldwide incidence of 25 major cancers in 1990.
AB  - The annual incidence rates (crude and age-standardized) and numbers of new cases
      of 25 different cancers have been estimated for the year 1990 in 23 areas of the
      world. The total number of new cancer cases (excluding non-melanoma skin cancer)
      was 8.1 million, just over half of which occur in the developing countries. The
      most common cancer in the world today is lung cancer, accounting for 18% of
      cancers of men worldwide, and 21% of cancers in men in the developed countries.
      Stomach cancer is second in frequency (almost 10% of all new cancers) and breast
      cancer, by far the most common cancer among women (21% of the total), is third.
      There are large differences in the relative frequency of different cancers by
      world area. The major cancers of developed countries (other than the 3 already
      named) are cancers of the colon-rectum and prostate, and in developing countries,
      cancers of the cervix uteri and esophagus. The implications of these patterns for
      cancer control, and specifically prevention, are discussed. Tobacco smoking and
      chewing are almost certainly the major preventable causes of cancer today.

PMID- 10074915
TI  - NTRK1 re-arrangement in papillary thyroid carcinomas of children after the
      Chernobyl reactor accident.
AB  - The prevalence of NTRK1 re-arrangement was determined in papillary thyroid
      carcinomas (PTCs) of children from Belarus who had been exposed to radioactive
      iodine after the Chernobyl reactor accident; 81 tumors were included, all of
      which were devoid of RET re-arrangement as analyzed in a current study on genomic
      alterations in PTC. Oncogenic fusion of the NTRK1 tyrosine kinase domain with the
      amino-terminal part of the tropomyosin gene (TPM3/NTRK1, trk) was observed in 5
      tumors. A single tumor exhibited a TPR/NTRK1 fusion (TRK-T2). Reciprocal
      NTRK1/TPM3 transcripts were found in 4 of 5 tumors with TPM3/NTRK1 re
      arrangement, indicating an intra-chromosomal balanced reciprocal inversion. No
      phenotypic differences from other post-Chernobyl childhood PTCs were detected. As
      compared with the high prevalence of RET re-arrangements reported for thyroid
      carcinomas of children after the Chernobyl reactor accident, NTRK1 re
      arrangements appear rare. Our results confirm that activation of receptor
      tyrosine kinase genes plays the predominant role in post-Chernobyl childhood
      thyroid carcinogenesis.

PMID- 10074916
TI  - Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis
      of European studies.
AB  - The relationship between hormonal therapy for menopause (hormone replacement
      therapy, HRT) and the risk of epithelial ovarian cancer was evaluated in a
      collaborative re-analysis of 4 European case-control studies, 2 conducted in
      Greece and 1 each in Italy and the United Kingdom, including a total of 1,470
      ovarian cancer cases and 3,271 hospital controls. Odds ratios (ORs) for HRT use
      were derived after allowance for study centre, age, socio-economic level, parity,
      menopausal status, type of menopause, age at menopause and oral contraceptive
      use. Overall, 109 (8.0%) ovarian cancer cases and 146 (4.7%) controls had ever
      used HRT, corresponding to an adjusted OR of 1.71 (95% confidence interval 1.30
      2.25). The point estimates of the OR were 1.77 in the first Greek study, 1.40 in
      the second Greek study, 1.66 in the Italian study and 1.68 in the British study.
      Adjustment for possible confounders, including menopausal status, type of
      menopause, age at menopause and oral contraceptive use, slightly increased the
      OR. Limiting the analysis to women with information on relevant aspects of HRT
      use revealed a weak positive association with duration and some evidence that the
      excess relative risk for ovarian cancer declined with time since last use. These
      findings are compatible with a promoting effect of HRT in ovarian carcinogenesis.
      It is also possible, however, that the positive association reflects chance or
      selective administration of HRT to high-risk individuals, since until recently in
      Europe HRT was prescribed mainly for alleviation of peri-menopausal symptoms.

PMID- 10074917
TI  - Risk of colorectal and other gastro-intestinal cancers after exposure to nitrate,
      nitrite and N-nitroso compounds: a follow-up study.
AB  - N-nitroso compounds are potent carcinogens detected in foodstuffs. The importance
      of dietary nitrosamines in relation to human cancer development is, however,
      uncertain. We studied the relationship between intake of nitrates, nitrites and N
      nitrosodimethylamine (NDMA) and risk of cancers of the gastro-intestinal tract in
      a cohort of 9,985 adult Finnish men and women. During a follow-up period of up to
      24 years, 189 gastro-intestinal cancer cases were diagnosed in the cohort,
      initially free from cancer. Intake of nitrate, nitrite and NDMA were estimated,
      based on food-consumption data from a 1-year dietary history interview covering
      the total diet of the participants. A significant positive association was
      observed between intake of NDMA and subsequent occurrence of colorectal cancer
      with a relative risk (RR) between the highest and lowest quartiles of intake of
      2.12 [95% confidence interval (CI) 1.04-4.33]. Of various sources of N-nitroso
      compounds, intake of smoked and salted fish was significantly (RR = 2.58, 95% CI
      1.21-5.51) and intake of cured meat was non-significantly (RR = 1.84, 95% CI 0.98
      3.47) associated with risk of colorectal cancer. No similar association was
      observed for intake of other fish or other meat. No significant associations were
      observed between NDMA intake and cancers of the head and neck combined or of the
      stomach or between nitrate or nitrite intake and risk of cancers of the gastro
      intestinal tract. Our results are in line with the idea that N-nitroso compounds
      can induce colorectal cancer in humans.

PMID- 10074918
TI  - Spectrum of transforming sequences detected by tumorigenicity assay in a large
      series of human neoplasms.
AB  - We here summarize the analysis of 126 DNA samples from patients with
      hematopoietic neoplasias and solid tumors and from various tumor cell lines that
      were screened in the tumorigenicity assay. Thirty-eight samples were able to
      induce tumors after transfection in NIH/3T3 cells and injection into nude mice.
      Southern-blot analysis with a panel of oncogene probes revealed human ras genes
      in the vast majority of cases (25 N-ras, 2 K-ras, 1 H-ras) but also activated
      FGF4, dbl, ret and mas genes respectively. DNA samples from the 6 remaining
      transfectants were cloned into EMBL-3 phages and screened with a human specific
      repetitive Alu probe. Direct hybridization of a transfectant cDNA library allowed
      cloning of the ufo oncogene. Application of the exon-trapping technique to alu
      positive phage DNA from the other transfectants enabled us to isolate tre, cot, B
      raf, p85beta/HUMORF8 and a novel oncogene.

PMID- 10074919
TI  - Increased resistance of GPx-1 transgenic mice to tumor promoter-induced loss of
      glutathione peroxidase activity in skin.
AB  - Reactive oxygen species formation is strongly suspected to play a role in
      multistep carcinogenesis, notably in tumor promotion. The tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) induces peroxide production, oxidative
      damage to DNA and inflammation in mouse skin. TPA is also known to cause a
      decrease in the activity of several antioxidant enzymes including glutathione
      peroxidases (GPx). The observation that several anti-oxidants can inhibit TPA
      mediated tumor promotion suggests that a decline in GPx activity could contribute
      to tumor promotion. We report here the effects of TPA on GPx activity in the skin
      of transgenic GPx mice that contain human GPx-1 transgenes under the regulation
      of a metallothionein IIA promoter. As expected, no significant difference in
      basal level of skin GPx activity was detected in the 3 lines of tg-MT-GPx mice
      investigated compared with non-transgenic controls. A single topical application
      of TPA induced gradually, over 20 hr, a small but detectable increase in GPx mRNA
      and protein levels in skin of non-transgenic mice and a contrasting decrease in
      both selenium-dependent and selenium-independent GPx activity. The extent of GPx
      induction was more pronounced in transgenic mice, and in contrast with non
      transgenic mice, no significant loss of GPx activity was observed in the TPA
      treated skin of these mice. Transgenic mice may, therefore, offer a novel model
      suitable to assess the role of GPx-1 in skin carcinogenesis, without the
      potential disadvantage of abnormally high levels of GPx activity produced
      constitutively in other transgenic models.

PMID- 10074920
TI  - Expression of multiple angiogenic cytokines in cultured normal human prostate
      epithelial cells: predominance of vascular endothelial growth factor.
AB  - The cytokines that regulate angiogenesis in normal and malignant prostate tissue
      are not well studied. Using an RT-PCR-based screen, we observed that cultured,
      low-passage normal human prostate epithelial cells (PrECs) express a variety of
      cytokines which have been shown to have angiogenic and/or endothelial cell
      activating properties in various systems. These include vascular endothelial
      growth factor (VEGF), basic fibroblastic growth factor (bFGF), transforming
      growth factor-alpha (TGF-alpha), transforming growth factor-beta (TGF-beta),
      interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), granulocyte
      macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating
      factor (G-CSF). Expression of VEGF, bFGF, GM-CSF, G-CSF, TGF-alpha and TNF-alpha
      in these cells was confirmed by immunohistochemistry. Culture medium conditioned
      by normal human PrECs for periods of up to 96 hr were found to contain VEGF, GM
      CSF, G-CSF, IL-8, TGF-beta1 and TGF-beta2 but not TNF-alpha or bFGF, as
      determined by ELISA. Of these, VEGF was by far the most prominently expressed
      angiogenic cytokine (approx. 2,500 pg/ml conditioned medium at 96 hr vs. 30 to
      100 pg/ml conditioned medium for the other cytokines). PrEC-conditioned medium
      induced an approximately 2-fold stimulation of [3H]-thymidine incorporation in
      cultured human umbilical cord endothelial cells (HUVECs) deprived of the
      endothelial growth factors VEGF and bFGF; this stimulation was abolished by
      neutralizing antibodies directed against VEGF but not bFGF, IL-8, GM-CSF or TNF
      alpha. VEGF expression by PrECs was not markedly altered by administration or
      deprivation of other angiogenic cytokines for which these cells have receptors,
      suggesting that there is not a hierarchy of cytokines controlling its expression;
      however, retinoic acid, a component of PrEC growth medium, was found to modestly
      suppress VEGF at physiological concentrations (0.1 ng/ml). These data suggest
      that normal PrECs express a variety of angiogenic cytokines, most prominently
      VEGF, to recruit a supporting vasculature, even in culture. Our data also suggest
      that the ability of malignant PrECs to stimulate angiogenesis may be intrinsic
      and does not need to be acquired during oncogenesis.

PMID- 10074922
TI  - Evidence that stress and surgical interventions promote tumor development by
      suppressing natural killer cell activity.
AB  - Stress and surgery have been suggested to compromise host resistance to
      infectious and malignant diseases in experimental and clinical settings. Because
      stress affects numerous physiological systems, the role of the immune system in
      mediating such effects is unclear. In the current study, we assessed the degree
      to which stress-induced alterations in natural killer (NK) cell activity underlie
      increased susceptibility to tumor development in F344 rats. Two stress paradigms
      were used: forced swim and abdominal surgery. Host resistance to tumor
      development was studied using 3 tumor models syngeneic to inbred F344 rats: CRNK
      16 leukemia and the MADB106 mammary adenocarcinoma, both sensitive to NK
      activity, and the NK-insensitive C4047 colon cancer. Swim stress increased CRNK
      16-associated mortality and metastatic development of MADB106 but not metastasis
      of C4047 cells. In both stress paradigms, stress suppressed NK activity (NKA) for
      a duration that paralleled its metastasis-enhancing effects on the MADB106 tumor.
      In vivo depletion of large granular lymphocyte/NK cells abolished the metastasis
      enhancing effects of swim stress but not of surgical stress. Our findings
      indicate that stress-induced suppression of NKA is sufficient to cause enhanced
      tumor development. Under certain stressful conditions, suppression of NKA is the
      primary mediator of the tumor-enhancing effects of stress, while under other
      conditions, additional factors play a significant role. Clinical circumstances in
      which surgical stress may induce enhanced metastatic growth are discussed.

PMID- 10074921
TI  - Hepatitis B virus X protein inhibits nucleotide excision repair.
AB  - Human hepatitis B virus (HBV) is a major risk factor of human hepatocellular
      carcinoma. Both in vivo and in vitro studies have shown that HBV X protein (HBx)
      can bind to the p53 tumor-suppressor protein and interfere with the role that p53
      plays in the cellular response to DNA damage. Our previous work has shown that
      HBx protein inhibits p53 sequence-specific transcriptional activation, p53
      mediated apoptosis and p53 binding to the TFIIH transcription-nucleotide excision
      repair (NER) factors, including XPB and XPD. To investigate whether HBx
      interferes with the NER pathway, we utilized cell-proliferation and colony
      formation assays to determine if cells expressing HBx are more sensitive to UVC
      induced DNA damage. NER was also measured by a plasmid host cell re-activation
      assay using a vector containing a luciferase reporter gene. UV-irradiated
      plasmids were transfected into a human RKO colon carcinoma cell line that
      contains wild-type (wt) p53 as well as its derivatives, either mutant p53-143ala
      (RKO-143ala) or human papillomavirus E6 (RKO-E6, a wt p53 protein that is rapidly
      degraded and non-functional). We found that cells expressing HBx are more
      sensitive to UVC-induced killing. Moreover, expression of HBx resulted in a
      reduction of NER efficiency in RKO cells to 52 +/- 2% (compared with control),
      RKO-143a1a cells to 46 +/- 3% and RKO-E6 cells to 60 +/- 3%. Similar results were
      also obtained with a HepG2 hepatoblastoma cell line carrying wt p53. In addition,
      we found that HBx bound directly to either XPB or XPD DNA helicase in vitro.
      Thus, our data indicate that HBx may interfere with the NER pathway through both
      p53-dependent and p53-independent mechanisms. Because HBx binds to TFIIH
      associated proteins, we propose that HBx may interfere with the NER pathway also
      through binding to and altering the activities of helicases necessary for NER
      and, thereby, increase the mutation rate induced by chemical carcinogens, such as
      aflatoxin B1, during human liver carcinogenesis.

PMID- 10074923
TI  - Induction of autocrine factor inhibiting cell motility from murine B16-BL6
      melanoma cells by alpha-melanocyte stimulating hormone.
AB  - We have previously reported that neuropeptide alpha-melanocyte stimulating
      hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic
      migration of B16-BL6 melanoma cells towards both fibronectin and laminin without
      affecting their growth. In the present study, we investigated the inhibitory
      mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked
      the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH
      did neither prevent the secretion of AMF from B16-BL6 cells nor alter the
      expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the
      secretion of the motility inhibitory factor(s) from B16-BL6 cells in a
      concentration- and time-dependent manner. The induction of the motility
      inhibitor(s) was proportional to increasing levels of intracellular cAMP induced
      by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate
      cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity
      in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have
      a m.w. below 3 kDa after fractionation. This activity was abolished by boiling
      but insensitive to trypsin. The treatment of tumor cells with cycloheximide
      reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha
      MSH inhibited the motility of B16-BL6 cells through induction of autocrine
      factor(s).

PMID- 10074924
TI  - High-affinity antibodies from hen's-egg yolks against human mannose-6
      phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R): characterization
      and potential use in clinical cancer studies.
AB  - The mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R)
      involved in trafficking of newly synthesized lysosomal enzymes, degradation of
      IGFII and activation of TGFbetaI, was suggested as being coded by a tumor
      suppressor gene. No specific antibodies are currently available for clinical
      studies. Since M6P/IGFII-R is a highly conserved protein in mammals, we immunized
      chicken with human M6P/IGFII-R. Up to 200 mg of specific IgY from weekly pooled
      egg yolk was extracted by the polyethylene glycol procedure. Chicken IgY
      antibodies specifically recognized the human and bovine 270-kDa M6P/IGFII-R but
      not the 46-kDa M6P-R, as documented by immunoprecipitation and immunobloting.
      Using biosensor analysis, IgY antibodies were shown to bind M6P/IGFII-R with high
      affinity (K(D) = 7.5 x 10(-9) M). A solid-phase competitive ELISA using bovine
      M6P/IGFII-R coated on 96-well microplates, allowed us to titrate the M6P/IGFII-R
      in human sera at a sensitivity of 300 ng/ml. The M6P/IGFII-R was stained by
      immunoperoxidase in breast- and ovarian-cancer cell lines (T47D, MDA-MB231, MCF7
      and BG1) and in frozen breast-cancer tissues, showing predominant localization in
      the trans-Golgi network. Staining specificity was shown with irrelevant IgY and
      by extinction with antigen excess. Quantitative immunohistochemical analysis of
      frozen sections from 40 invasive breast carcinomas indicated varying levels (from
      5 to 400 units) of the M6P/IGFII-R protein which were not correlated with tumor
      size, histological grade and estrogen receptor or progesterone receptor. There
      was a trend (p = 0.08) between lymph-node invasiveness and low receptor level.
      Moreover, the M6P/IGFII-R level was significantly lower in cancer cells than in
      normal cells in 10 out of the 21 tumors in which the peritumoral normal glands
      could be quantified in parallel. These 2 last results agree with the hypothesis
      of a tumor-suppressor gene for this receptor and suggest more basic and clinical
      studies to prove it.

PMID- 10074925
TI  - Detailed marker chromosome analysis in cell line U-BLC1, established from
      transitional-cell carcinoma of the bladder.
AB  - A permanent cell line, U-BLC1, was established from a primary transitional-cell
      carcinoma, TCC, of the urinary bladder. Karyotype analysis showed the line to be
      highly aberrant, with a near-triploid chromosome number of 68 to 73. Comparative
      genomic hybridization revealed some distinct differences between the primary
      tumor and the established cell line. Karyotype analysis showed 3 marker
      chromosomes with homogeneously staining regions, HSRs, in the cell line. The HSRs
      were isolated by microdissection and the microdissection probes were hybridized
      to normal metaphase chromosomes. The HSRs contain sequences known to be
      frequently involved in amplification in transitional-cell carcinoma of the
      bladder, 6p22, 7p11-p12, 9p23-pter, and one region not yet reported to be
      amplified in primary TCC of the bladder, 1p31-p32. A candidate-gene approach
      showed that in the region 7p11-p12 the EGFR locus is amplified and highly
      expressed.

PMID- 10074926
TI  - Growth inhibition of ras-dependent tumors in nude mice by a potent ras-dislodging
      antagonist.
AB  - A lipophilic farnesyl moiety attached to the carboxyl terminal cysteine of ras
      proteins structurally supports their membrane anchorage, required for ras
      dependent growth-factor signaling and for transforming activity of ras
      oncoproteins. It has been shown that inhibition of ras farnesylation can block
      tumor growth in nude mice but that some ras-dependent tumors escape such blockage
      as a result of prenylation of ras. S-trans-transfarnesylthiosalicylic acid (FTS)
      is a potent ras-dislodging antagonist that does not affect ras prenylation but
      rather acts on the mature, membrane-bound ras and facilitates its degradation.
      Here we demonstrate that FTS induces reappearance of stress fibers in H-ras
      transformed rat-1 cells (EJ cells) in vitro, inhibits their anchorage-independent
      growth in vitro, and blocks EJ-tumor growth in nude mice. The anchorage
      independent growth of cells expressing ErbB2 (B104), but not that of v-raf
      transformed cells, is also inhibited by FTS, suggesting specificity towards
      activated ras. FTS treatment (5 mg/kg i.p. daily) caused inhibition (75-80%) of
      tumor growth in nude mice implanted with EJ, but not in mice implanted with v-raf
      transformed cells, with no evidence of systemic toxicity. Moreover, FTS treatment
      increased the survival rate of EJ-tumor-bearing mice from 48 to 68 days. Here we
      demonstrate anti-tumor potency in a synthetic, non-toxic, ras-dislodging
      antagonist acting independently of farnesyltransferases.

PMID- 10074927
TI  - Detection of mutations in the DNA polymerase delta gene of human sporadic
      colorectal cancers and colon cancer cell lines.
AB  - To test the hypothesis whether DNA polymerases acquire mutator properties during
      tumor development (mutator hypothesis), we examined DNA polymerase delta mRNA in
      6 colon cancer cell lines (DLD-1, HCT116, SW48, HT29, SW480 and SW620) and 7
      sporadic human colorectal cancers. For analysis we used amplification of cDNA by
      polymerase chain reaction, single-strand conformation polymorphism and sequencing
      techniques. In 5 of the cell lines, 9 mutations leading to changes of the amino
      acid sequence of DNA polymerase delta were detected. Most mutations were found in
      the cell lines DLD-1, HCT116 and SW48 for which defects in mismatch repair genes
      had been identified previously. In the majority of cases, wild type and mutated
      sequences were present. In 2 cell lines (HCT116 and SW48), a single-nucleotide
      deletion occurred at the same position. This resulted in a premature termination
      codon by which the DNA interaction domain of the enzyme was eliminated.
      Furthermore, sequence deviations were found in the tumor tissues of 4 colon
      cancer patients. Wild-type and altered sequences were present simultaneously. The
      deviations included missense mutations (2 cases) and silent mutations (2 cases).
      The missense mutations and one of the silent mutations were found in normal
      mucosa as well. In addition, the mutation clustered region of a tumor suppressor
      gene, often found to be defective in colon cancer, the adenomatous polyposis coli
      (APC) gene, was investigated in surgical specimens and cell lines. One carcinoma
      and 2 cell lines exhibited amino acid changes in both the DNA polymerase delta
      gene and in the mutation clustered region of the APC gene. Since most of the
      mutations detected in the DNA polymerase delta mRNA are likely to alter the
      structure of the protein, the enzyme is expected to be functionally impaired. In
      particular, copying fidelity might be decreased, thus contributing to the high
      mutation rate observed in colorectal cancer.

PMID- 10074928
TI  - Expression of alternatively spliced mdm2 transcripts correlates with stabilized
      wild-type p53 protein in human glioblastoma cells.
AB  - A puzzling finding in various human tumors, including glioblastoma multiforme
      (GBM), is the stabilization of wild-type (wt) p53 protein. The biological
      significance of this phenomenon and the mechanism by which it occurs are
      unexplained. Recent reports have revealed that mdm2 exerts its negative
      regulation on the p53 signal by directly binding p53 protein and thereby
      instigating its proteasomal degradation. mdm2 has been shown to exist in
      alternatively spliced forms in human ovarian and bladder carcinomas, and recently
      in GBM, with loss or disruption of its p53 binding domain. Here we report that
      alternatively spliced transcripts of mdm2 are present in 7 of 16 human GBM
      primary cell cultures and in the established GBM cell lines LN 229 and LN 18.
      Sequencing demonstrated loss of the amino terminal p53 binding domain in these
      alternatively spliced mdm2 transcripts, and an out-of-frame splicing in the
      majority of cases. A significant correlation between the presence of mdm2 splice
      variants and increased expression of wt p53 protein was observed. Furthermore, in
      the presence of an mdm2 splice variant, wt p53 stabilization occurred despite
      coincident MDM2 amplification. Our findings suggest that wt p53 protein
      stabilization may arise as a consequence of alternative splicing of mdm2. Such a
      mechanism might account for wt p53 protein accumulation in GBM cells, even in the
      presence of MDM2 gene amplification.

PMID- 10074929
TI  - Retinoic acid-mediated growth inhibition of small cell lung cancer cells is
      associated with reduced myc and increased p27Kip1 expression.
AB  - Human lung cancer cells, including small cell lung carcinoma (SCLC), frequently
      lose expression of retinoic acid receptor beta (RAR-beta) and are resistant to
      the growth inhibitory activity of all-trans retinoic acid (RA). To elucidate the
      role of RAR-beta in the growth regulation of SCLC by retinoids, we restored RAR
      beta expression in RAR-beta-negative H209 SCLC cells by retroviral transduction
      (H209-RAR-beta). We found that H209-RAR-beta, but not parental H209 cells,
      underwent growth inhibition upon RA treatment. RA-treated H209-RAR-beta cells
      arrested in G1 and displayed reduced L-myc expression and cyclin-dependent kinase
      2 (cdk2) activity compared with untreated cells. RA treatment of H209-RAR-beta
      cells was also accompanied by increased expression of the cdk inhibitor p27Kip1,
      whereas no differences in the expression of L-myc or p27Kip1 were detected upon
      RA treatment of parental H209 cells. The RA-induced growth arrest of H82 SCLC
      cells, which express endogenous RAR-beta, was also associated with reduced c-myc
      and increased p27Kip1 expression. We found that ectopic expression of p27Kip1
      induced growth inhibition in both H209 and H82 cells, and that sustained myc
      expression in H209-RAR-beta cells promoted the induction of apoptosis upon RA
      addition. Our observations indicate that RAR-beta gene transfer can restore RA
      sensitivity in SCLC cells and suggest that myc and p27Kip1 may represent critical
      mediators of the RA-induced cell cycle arrest in SCLC cells expressing RAR-beta.

PMID- 10074930
TI  - Absence of intragenic mismatch mutations in small cell lung cancers with
      microsatellite instability.

PMID- 10074931
TI  - Malaria surveillance--United States, 1995.
AB  - PROBLEM/CONDITION: Malaria is caused by four species of Plasmodium (i.e., P.
      falciparum, P. vivax, P. ovale, or P. malariae), which are transmitted by the
      bite of an infective female Anopheles sp. mosquito. Most malaria infections in
      the United States occur among persons who have traveled to areas with ongoing
      transmission. Occasionally, cases occur in the United States through exposure to
      infected blood products, by congenital transmission, or by local mosquito-borne
      transmission. Malaria surveillance is conducted to identify episodes of local
      transmission and to guide prevention recommendations for travelers. REPORTING
      PERIOD: Cases with onset of illness during 1995. DESCRIPTION OF SYSTEM: Malaria
      cases confirmed by blood smears are reported to local and/or state health
      departments by health-care providers and/or laboratory staff. Case investigations
      are conducted by local and/or state health departments, and reports are
      transmitted to CDC through the National Malaria Surveillance System (NMSS). Data
      from NMSS serve as the basis for this report. RESULTS: CDC received reports of
      1,167 cases of malaria with onset of symptoms during 1995 among persons in the
      United States or one of its territories. This number represents an increase of
      15% from the 1,014 cases reported for 1994. P. vivax, P. falciparum, P. malariae,
      and P. ovale were identified in 48.2%, 38.6%, 3.9%, and 2.2% of cases,
      respectively. More than one species was present in three patients (0.3% of
      total). The infecting species was not determined in 80 (6.9%) cases. The number
      of reported malaria cases acquired in Africa (n=519) remained approximately the
      same as in 1994 (n=517); cases acquired in Asia increased by 32.4% (n=335); and
      cases acquired in the Americas increased by 37.4 % (n=246). Of 591 U.S. civilians
      who acquired malaria abroad, 15.6% had followed a chemoprophylactic drug regimen
      recommended by CDC for the area where they had traveled. Nine patients became
      infected in the United States. Of these nine cases, five were congenitally
      acquired; one was acquired by organ transplantation; and one was acquired by a
      blood transfusion. For two of the nine cases, the source of infection was
      unknown. Six deaths were attributed to malaria. INTERPRETATION: The 15% increase
      in malaria cases in 1995 compared with 1994 resulted primarily from increases in
      cases acquired in Asia and the Americas, most notably a 100% increase in the
      number of cases reported from South America. This change could have resulted from
      local changes in disease transmission, travel patterns, reporting errors, or a
      decreased use of effective antimalarial chemoprophylaxis. In most reported cases,
      U.S. civilians who acquired infection abroad were not on an appropriate
      chemoprophylaxis regimen for the country where they acquired malaria. ACTIONS
      TAKEN: Additional information was obtained concerning the six fatal cases and the
      nine infections acquired in the United States. Malaria prevention guidelines were
      updated and distributed to health-care providers. Persons traveling to a
      malarious area should take the recommended chemoprophylaxis regimen and use
      personal protection measures to prevent mosquito bites. Any person who has been
      to a malarious area and who subsequently develops a fever or influenza-like
      symptoms should seek medical care; investigation should include a blood smear for
      malaria. Malaria infections can be fatal if not diagnosed and treated promptly.
      Recommendations concerning prevention and treatment of malaria can be obtained
      from CDC.

PMID- 10074932
TI  - NO news is not necessarily good.

PMID- 10074933
TI  - Protein folding as seen from water's perspective.

PMID- 10074934
TI  - Intricacies of ribosomal frameshifting.

PMID- 10074935
TI  - Leadzyme RNA catalysis.

PMID- 10074936
TI  - Astbury and the alpha-helix.

PMID- 10074937
TI  - Picture story. An SH2 domain in disguise.

PMID- 10074938
TI  - Solution structure of the loop B domain from the hairpin ribozyme.
AB  - The hairpin ribozyme is a small catalytic RNA with a unique two-domain structure.
      Here we present the solution structure of the loop B domain of the hairpin
      ribozyme, which contains most of the catalytically essential nucleotides. The 38
      nucleotide domain contains a 16-nucleotide internal loop that forms one of the
      largest non-Watson-Crick segments of base pairing thus far determined by either
      NMR or crystallography. Since the solution structure of the smaller loop A domain
      has been previously solved, an NMR structure-based model of the 22,000 Mr hairpin
      ribozyme-substrate open complex emerges by joining the two domain structures.
      Strikingly, catalytically essential functional groups for the loop B domain are
      concentrated within an expanded minor groove, presenting a clear docking surface
      for the loop A domain.

PMID- 10074939
TI  - Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity
      of collagenase inhibitors.
AB  - The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP
      13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for
      understanding the selectivity profile of a novel series of matrix metalloprotease
      (MMP) inhibitors. Differences in the relative size and shape of the MMP S1'
      pockets suggest that this pocket is a critical determinant of MMP inhibitor
      selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating
      large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1'
      pocket must undergo a conformational change to accommodate comparable P1' groups.
      The selectivity of the diphenylether series of inhibitors for collagenase-3 is
      largely determined by their affinity for the preformed S1' pocket of collagenase
      3, as compared to the induced fit in collagenase-1.

PMID- 10074940
TI  - The molecular basis for protein kinase A anchoring revealed by solution NMR.
AB  - Compartmentalization of signal transduction enzymes into signaling complexes is
      an important mechanism to ensure the specificity of intracellular events.
      Formation of these complexes is mediated by specialized protein motifs that
      participate in protein-protein interactions. The adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent protein kinase (PKA) is localized through
      interaction of the regulatory (R) subunit dimer with A-kinase-anchoring proteins
      (AKAPs). We now report the solution structure of the type II PKA R-subunit
      fragment RIIalpha(1-44), which encompasses both the AKAP-binding and dimerization
      interfaces. This structure incorporates an X-type four-helix bundle dimerization
      motif with an extended hydrophobic face that is necessary for high-affinity AKAP
      binding. NMR data on the complex between RIIalpha(1-44) and an AKAP fragment
      reveals extensive contacts between the two proteins. Interestingly, this same
      dimerization motif is present in other signaling molecules, the S100 family.
      Therefore, the X-type four-helix bundle may represent a conserved fold for
      protein-protein interactions in signal transduction.

PMID- 10074941
TI  - Crystal structure of a scavenger receptor cysteine-rich domain sheds light on an
      ancient superfamily.
AB  - Scavenger receptor cysteine-rich (SRCR) domains are found widely in cell surface
      molecules and in some secreted proteins, where they are thought to mediate ligand
      binding. We have determined the crystal structure at 2.0 A resolution of the SRCR
      domain of Mac-2 binding protein (M2BP), a tumor-associated antigen and matrix
      protein. The structure reveals a curved six-stranded beta-sheet cradling an alpha
      helix. Structure-based sequence alignment demonstrates that the M2BP SRCR domain
      is a valid template for the entire SRCR protein superfamily. This allows an
      interpretation of previous mutagenesis data on ligand binding to the lymphocyte
      receptor CD6.

PMID- 10074942
TI  - Structural characterization of nitric oxide synthase isoforms reveals striking
      active-site conservation.
AB  - Crystal structures of human endothelial nitric oxide synthase (eNOS) and human
      inducible NOS (iNOS) catalytic domains were solved in complex with the arginine
      substrate and an inhibitor S-ethylisothiourea (SEITU), respectively. The small
      molecules bind in a narrow cleft within the larger active-site cavity containing
      heme and tetrahydrobiopterin. Both are hydrogen-bonded to a conserved glutamate
      (eNOS E361, iNOS E377). The active-site residues of iNOS and eNOS are nearly
      identical. Nevertheless, structural comparisons provide a basis for design of
      isozyme-selective inhibitors. The high-resolution, refined structures of eNOS
      (2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural
      zinc situated at the intermolecular interface and coordinated by four cysteines,
      two from each monomer.

PMID- 10074943
TI  - Structural and mechanistic basis of immunity toward endonuclease colicins.
AB  - The crystal structure of the cytotoxic endonuclease domain from the bacterial
      toxin colicin E9 in complex with its cognate immunity protein Im9 reveals that
      the inhibitor does not bind at the active site, the core of which comprises the
      HNH motif found in intron-encoded homing endonucleases, but rather at an adjacent
      position leaving the active site exposed yet unable to bind DNA because of steric
      and electrostatic clashes with incoming substrate. Although its mode of action is
      unorthodox, Im9 is a remarkably effective inhibitor since it folds within
      milliseconds and then associates with its target endonuclease at the rate of
      diffusion to form an inactive complex with sub-femtomolar binding affinity. This
      hyperefficient mechanism of inhibition could be well suited to other toxic enzyme
      systems, particularly where the substrate is a polymer extending beyond the
      boundaries of the active site.

PMID- 10074944
TI  - Hydration of denatured and molten globule proteins.
AB  - The hydration of nonnative states is central to protein folding and stability but
      has been probed mainly by indirect methods. Here we use water 17O relaxation
      dispersion to monitor directly the internal and external hydration of alpha
      lactalbumin, lysozyme, ribonuclease A, apomyoglobin and carbonic anhydrase in
      native and nonnative states. The results show that nonnative proteins are more
      structured and less solvent exposed than commonly believed. Molten globule
      proteins preserve most of the native internal hydration sites and have native
      like surface hydration. Proteins denatured by guanidinium chloride are not fully
      solvent exposed but contain strongly perturbed occluded water. These findings
      shed new light on hydrophobic stabilization of proteins.

PMID- 10074945
TI  - Crystal structure of a lead-dependent ribozyme revealing metal binding sites
      relevant to catalysis.
AB  - The leadzyme is a small RNA motif that catalyzes a site-specific, Pb2+-dependent
      cleavage reaction. As such, it is an example of a metal-dependent RNA enzyme.
      Here we describe the X-ray crystallographic structure of the leadzyme, which
      reveals two independent molecules per asymmetric unit. Both molecules feature an
      internal loop in which a bulged purine base stack twists away from the helical
      stem. This kinks the backbone, rendering the phosphodiester bond susceptible to
      cleavage. The independent molecules have different conformations: one leadzyme
      copy coordinates Mg2+, whereas the other binds only Ba2+ or Pb2+. In the active
      site of the latter molecule, a single Ba2+ ion coordinates the 2'-OH nucleophile,
      and appears to mimic the binding of catalytic lead. These observations allow a
      bond cleavage reaction to be modeled, which reveals the minimal structural
      features necessary for catalysis by this small ribozyme.

PMID- 10074946
TI  - Structural and energetic origins of indirect readout in site-specific DNA
      cleavage by a restriction endonuclease.
AB  - Specific recognition by EcoRV endonuclease of its cognate, sharply bent GATATC
      site at the center TA step occurs solely via hydrophobic interaction with thymine
      methyl groups. Mechanistic kinetic analyses of base analog-substituted DNAs at
      this position reveal that direct readout provides 5 kcal mol(-1) toward
      specificity, with an additional 6-10 kcal mol(-1) arising from indirect readout.
      Crystal structures of several base analog complexes show that the major-groove
      hydrophobic contacts are crucial to forming required divalent metal-binding
      sites, and that indirect readout operates in part through the sequence-dependent
      free-energy cost of unstacking the center base-pair step of the DNA.

PMID- 10074947
TI  - Crystal structure of a phospholipase D family member.
AB  - The first crystal structure of a phospholipase D (PLD) family member has been
      determined at 2.0 A resolution. The PLD superfamily is defined by a common
      sequence motif, HxK(x)4D(x)6GSxN, and includes enzymes involved in signal
      transduction, lipid biosynthesis, endonucleases and open reading frames in
      pathogenic viruses and bacteria. The crystal structure suggests that residues
      from two sequence motifs form a single active site. A histidine residue from one
      motif acts as a nucleophile in the catalytic mechanism, forming a phosphoenzyme
      intermediate, whereas a histidine residue from the other motif appears to
      function as a general acid in the cleavage of the phosphodiester bond. The
      structure suggests that the conserved lysine residues are involved in phosphate
      binding. Large-scale genomic sequencing revealed that there are many PLD family
      members. Our results suggest that all of these proteins may possess a common
      structure and catalytic mechanism.

PMID- 10074948
TI  - Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting
      viral pseudoknot.
AB  - Many viruses regulate translation of polycistronic mRNA using a -1 ribosomal
      frameshift induced by an RNA pseudoknot. A pseudoknot has two stems that form a
      quasi-continuous helix and two connecting loops. A 1.6 A crystal structure of the
      beet western yellow virus (BWYV) pseudoknot reveals rotation and a bend at the
      junction of the two stems. A loop base is inserted in the major groove of one
      stem with quadruple-base interactions. The second loop forms a new minor-groove
      triplex motif with the other stem, involving 2'-OH and triple-base interactions,
      as well as sodium ion coordination. Overall, the number of hydrogen bonds
      stabilizing the tertiary interactions exceeds the number involved in Watson-Crick
      base pairs. This structure will aid mechanistic analyses of ribosomal
      frameshifting.

PMID- 10074949
TI  - Cadaveric organ donation: rethinking SPRT. Selection of Potential Recipients of
      Transplants.

PMID- 10074950
TI  - Generic substitution and optimal patient care.

PMID- 10074951
TI  - Cadaveric organ donation: rethinking donor motivation.

PMID- 10074952
TI  - Predictors of survival after deep vein thrombosis and pulmonary embolism: a
      population-based, cohort study.
AB  - BACKGROUND: Because reported survival after venous thromboembolism (VTE) varies
      widely, we performed a population-based retrospective cohort study to estimate
      survival, compare observed with expected survival, and determine predictors of
      short-term (< or =7 days) and long-term survival (>7 days) after VTE. METHODS: We
      followed the 25-year (1966-1990) inception cohort (n = 2218) of Olmsted County,
      Minnesota, patients with deep vein thrombosis alone (DVT) or pulmonary embolism
      with or without deep vein thrombosis (PE+/-DVT) forward in time until death or
      the last clinical contact. RESULTS: During 14 629 person-years of follow-up, 1333
      patients died. Seven-day, 30-day, and 1-year VTE survival rates were 74.8% (DVT,
      96.2%; PE+/-DVT, 59.1%), 72.0% (DVT, 94.5%; PE+/-DVT, 55.6%), and 63.6% (DVT,
      85.4%; PE+/-DVT, 47.7%), respectively. Observed survival after DVT, PE+/-DVT, and
      overall was significantly worse than expected for Minnesota whites of similar age
      and sex (P<.001). More than one third of deaths occurred on the date of onset or
      after VTE that was unrecognized during life. Short-term survival improved during
      the 25-year study period, while long-term survival was unchanged. After adjusting
      for comorbid conditions, PE+/-DVT was an independent predictor of reduced
      survival for up to 3 months after onset compared with DVT alone. Other
      independent predictors of both short- and long-term survival included age, body
      mass index, patient location at onset, malignancy, congestive heart failure,
      neurologic disease, chronic lung disease, recent surgery, and hormone therapy.
      Additional independent predictors of long-term survival included tobacco smoking,
      other cardiac disease, and chronic renal disease. CONCLUSIONS: Survival after
      VTE, and especially after PE+/-DVT, is much worse than reported, and
      significantly less than expected survival. Compared with DVT alone, symptomatic
      PE+/-DVT is an independent predictor of reduced survival for up to 3 months after
      onset, implying that treatment for the 2 disorders should be different.

PMID- 10074953
TI  - Prediction of the risk of bleeding during anticoagulant treatment for venous
      thromboembolism.
AB  - OBJECTIVES: To construct and validate the bleeding risk prediction score, which
      is based on variables identified in the literature that can be easily obtained
      before the institution of anticoagulant therapy, in a large independent cohort of
      patients who were treated with anticoagulant therapy for established venous
      thromboembolism to allow for quantitative assessment of the risks and benefits of
      the therapy and to adapt the patient's management accordingly. METHODS: We
      constructed a bleeding risk prediction score, based on variables and their odds
      ratios identified in the literature, which can be easily obtained before the
      institution of anticoagulant therapy (score = [ 1.6 X age] + [1.3 x sex] + [2.2 X
      malignancy]). Subsequently, we evaluated the score in a test group of 241
      patients treated with anticoagulant therapy for venous thromboembolism to
      determine the optimal cutoff points for the prediction of hemorrhagic
      complications, using receiver operating characteristic curve analysis. We then
      validated this score in an independent cohort of 780 patients. A score of 3 or
      more points, 1 to 3 points, or 0 points represented a high, intermediate, or low
      bleeding risk, respectively. RESULTS: The score in about one fifth of the
      patients in the test group was classified as predicting high risk for bleeding
      complications. The risk of all bleeding complications was 26% in this group and
      the risk of major bleeding complications was 14%. The area under the curve was
      0.75 (95% confidence interval, 0.64-0.84) and 0.82 (95% confidence interval, 0.66
      0.98) for all bleeding complications and major bleeding complications,
      respectively. When validated, there was a moderate loss of predictive power of
      the score, but the categorization of the patients by the score remained
      clinically useful; 20% of the patients were classified as high risk, and the
      bleeding rate was 17% for all bleeding complications and 7% for major bleeding
      complications compared with 4% and 1%, respectively, in those categorized as low
      risk. CONCLUSIONS: With the use of 3 easily obtainable, clinical variables in a
      prediction model, it is possible to identify a subgroup of patients at the start
      of anticoagulant therapy who have a high risk of developing hemorrhagic
      complications. Further studies should address whether additional measures to
      prevent bleeding decrease the bleeding incidence without compromising efficacy.

PMID- 10074954
TI  - Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in
      Denmark.
AB  - BACKGROUND: Both morbidity and mortality resulting from Staphylococcus aureus
      endocarditis are known to be high, and the incidence of this disease seems to
      increase. The Statens Serum Institut, Copenhagen, Denmark, made it possible for
      us to analyze the clinical features of S aureus endocarditis in a nation-wide
      population of non-drug addicts. METHODS: Almost all Danish cases of bacteremia
      due to S aureus are reported to the Staphylococcus laboratory, Statens Serum
      Institut. The medical records were reviewed in cases reported from 1982 to 1991
      in which the diagnosis of endocarditis was reported or suspected. RESULTS: A
      total of 260 patients, 145 males and 115 females, fulfilled the diagnostic
      criteria. The median age was 67.5 years. In 83 patients, the diagnosis of
      endocarditis was not suspected clinically. The overall mortality rate among those
      patients whose disease was diagnosed clinically was 46%. Among the subset of
      patients who received medical therapy only and appropriate antistaphylococcal
      treatment, mortality was significantly associated with late congestive heart
      failure, age, and involvement of the central nervous system. CONCLUSIONS: A
      raised awareness of the paucity of clinical findings and a more frequent use of
      echocardiography as a screening method seem essential to improve the prognosis of
      patients with S aureus endocarditis. Involvement of the central nervous system
      constitutes a relative indication of early valve replacement.

PMID- 10074955
TI  - Infective endocarditis due to Staphylococcus aureus: deleterious effect of
      anticoagulant therapy.
AB  - BACKGROUND: The use of anticoagulant therapy in patients with infective
      endocarditis (IE) is a controversial issue. OBJECTIVE: To study the impact of
      anticoagulant therapy on the clinical outcome, mortality, and cause of death in a
      series of patients with native and prosthetic left-sided Staphylococcus aureus
      IE. METHODS: This report is based on all consecutive cases of IE diagnosed at our
      hospital between 1975 to 1997. Clinical data, including the use of anticoagulant
      therapy at the time of diagnosis, were prospectively obtained, and antibiotic
      treatment and surgical indications were uniform throughout the study period.
      Computed tomographic scans of all clinical records were reviewed. RESULTS: Of 637
      consecutive patients with IE, 56 had left-sided S aureus IE affecting native
      valves in 35 patients and prosthetic valves in 21 patients. Of the patients with
      prosthetic valve IE, 19 (90%) were taking oral anticoagulant therapy at the time
      of diagnosis while no patient with native valve IE was receiving such treatment.
      There were no differences between native valve IE and prosthetic valve IE in age,
      sex, embolic episodes, and number of central nervous system complications.
      Mortality was higher in prosthetic valve IE than in native valve IE (71% vs 37%;
      P=.02). No patient with native valve IE died due to central nervous system
      complications, while 73% (11 of 15 patients) with prosthetic valve IE died due to
      central nervous system complications. The difference in the distribution of the
      type of death (stroke vs other) was significant (P<.007). CONCLUSIONS: Our
      results suggest that in left-sided S aureus IE anticoagulant therapy is closely
      associated with death due to neurologic damage. According to our data, as soon as
      the clinical diagnosis of S aureus IE is indicated the use of anticoagulant
      therapy should be immediately stopped until the septic phase of the disease is
      overcome.

PMID- 10074956
TI  - Thrombosis in the emergency department: use of a clinical diagnosis model to
      safely avoid the need for urgent radiological investigation.
AB  - CONTEXT: The management of patients presenting to hospital emergency departments
      with suspected deep vein thrombosis (DVT) is problematic because urgent
      diagnostic imaging capability is sometimes unavailable. Experienced physicians
      using clinical skills alone can classify patients with suspected DVT into low-,
      moderate-, and high-probability categories. OBJECTIVES: To determine the accuracy
      of an explicit clinical model for the diagnosis of DVT when applied by emergency
      department physicians and to assess the safety and feasibility of a management
      strategy based on the clinical pretest probability for patients presenting to the
      emergency department with suspected DVT outside of regular hospital staff work
      hours. METHODS: A prospective cohort study was performed in the emergency
      departments of 2 tertiary care institutions involving 344 patients with suspected
      DVT. Patient conditions were evaluated by an emergency department physician who
      determined the pretest probability for DVT to be low, moderate, or high using an
      explicit clinical model. Patients for whom DVT was considered a low pretest
      probability were discharged from the emergency department and returned the
      following day for venous compression ultrasound imaging of the affected leg.
      Patients for whom DVT was considered a moderate pre-test probability received a
      single, weight-adjusted dose of subcutaneous unfractionated heparin sodium
      (between 12 500 and 20 000 U), were discharged from the emergency department, and
      returned the next morning to undergo ultrasonography. Patients for whom DVT was
      considered a high pretest probability were admitted to the hospital, administered
      intravenous unfractionated heparin, and ultrasonography was arranged within 24
      hours. Patients with positive ultrasonographic findings were diagnosed with DVT,
      except for those with low pretest probability for whom confirmatory venography
      was performed. Patients with DVT excluded in the initial evaluation period did
      not receive anticoagulant therapy. All patients were followed up for 90 days to
      monitor development of thromboembolic or bleeding complications. RESULTS: Twenty
      four (49.0% [95% confidence interval (CI), 34.5%-63.6%]) of 49 patients in the
      high-probability category, 15 (14.3% [95% CI, 8.3%-22.4%]) of 105 in the moderate
      , and 6 (3.2% [95% CI, 1.2%-6.7%]) of 190 in the low-probability category were
      confirmed to have DVT. Overall, 45 (13.1%) of 344 patients were confirmed to have
      DVT. No patient developed pulmonary embolism or major bleeding complications
      within 48 hours of initial evaluation in the emergency department. Of the 301
      patients who had DVT excluded during the initial evaluation period, only 2 (0.7%
      [95% CI, 0.1%-2.3%]) developed venous thromboembolic complications (calf vein
      thromboses in both) in the 3-month follow-up period. CONCLUSIONS: Using an
      explicit clinical model, emergency department physicians can accurately classify
      patients with suspected DVT into high-, moderate-, and low-probability groups. A
      management plan based on probability for DVT that avoids the need for urgent
      diagnostic imaging is safe and feasible in the emergency department setting.

PMID- 10074957
TI  - Depression, falls, and risk of fracture in older women. Study of Osteoporotic
      Fractures Research Group.
AB  - BACKGROUND: Previous studies have suggested that depression is associated with
      falls and with low bone density, but it is not known whether depression leads to
      an increased risk of fracture. SUBJECTS AND METHODS: We conducted a prospective
      cohort study in elderly white women who were recruited from population-based
      listings in the United States. At a second visit (1988-1990), 7414 participants
      completed the 15-item Geriatric Depression Scale and were considered depressed if
      they reported 6 or more symptoms of depression. We measured bone mineral density
      (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second
      visit, and asked participants about incident falls (yes/no) at 4 follow-up
      visits. Nonvertebral fractures were ascertained for an average of 6 years
      following the depression measure, and verified radiologically. We determined
      incident vertebral fractures by comparing lateral spine films obtained at the
      first visit (1986-1988) with repeat films obtained an average of 3.7 years later
      (1991-1992). RESULTS: The prevalence of depression (Geriatric Depression Scale
      score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the
      hip and lumbar spine in women with depression compared with those without
      depression. Women with depression were more likely to experience subsequent falls
      than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95%
      confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after
      adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004).
      Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2
      1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman
      years of follow-up) compared with women without depression (1367 fractures in 59
      503 woman-years of follow-up). This association remained strong after adjusting
      for potential confounding variables, including medication use and neuromuscular
      function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent
      falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P =
      .06). Women with depression were also more likely to suffer vertebral fractures
      than women without depression, adjusting for history of vertebral fracture,
      history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental
      calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001).
      CONCLUSIONS: Depression is a significant risk factor for fracture in older women.
      The greater frequency of falls among individuals with depression partially
      explains this finding. Other mechanisms responsible for the association between
      depression and fracture remain to be determined.

PMID- 10074958
TI  - Minocycline and lupuslike syndrome in acne patients.
AB  - BACKGROUND: Recently several case reports described the association between
      minocycline and lupuslike syndrome. Minocycline, one of the tetracyclines, is
      widely used to treat acne. We aimed to examine the association of exposure to
      minocycline and other tetracyclines with the development of lupuslike syndrome.
      METHODS: We conducted a nested case-control study in a cohort of 27 688 acne
      patients aged 15 to 29 years, using data automatically recorded on general
      practitioners' office computers in the United Kingdom. Controls were matched to
      cases on age, sex, and practice. The main outcome was lupuslike syndrome defined
      as the occurrence of polyarthritis or polyarthralgia of unknown origin, with
      negative rheumatoid factor or latex agglutination test, positive or unmeasured
      antinuclear factor, elevated or unmeasured erythrocyte sedimentation rate, and
      absence of or unmeasured antinative DNA antibody levels. RESULTS: We identified
      29 cases and selected 152 controls. Current single use of minocycline was
      associated with an 8.5-fold (95% confidence interval [CI], 2.1-35) increased risk
      of developing lupuslike syndrome compared with non-users and past users of
      tetracyclines combined. The risk of past exposure to any of the tetracyclines was
      closely similar to nonuse (relative risk, 1.3; 95% CI, 0.5-3.3). Current use of
      doxycycline, oxytetracycline, or tetracycline combined was associated with a 1.7
      fold (95% CI, 0.4-8.1) increase of risk. The risk increased with longer use.
      CONCLUSION: Current use of minocycline increased the risk of developing lupuslike
      syndrome 8.5-fold in the cohort of young acne patients. The effect was stronger
      in longer-term users. However, the absolute risk of developing lupuslike syndrome
      seems to be relatively low.

PMID- 10074959
TI  - Plasma insulin levels and incidence of hypertension in African Americans and
      whites.
AB  - BACKGROUND: Hyperinsulinemia may play an important role in the pathogenesis of
      hypertension in whites but the role of hyperinsulinemia in hypertension in
      African Americans is controversial. SUBJECTS AND METHODS: We studied the
      relationship between insulin levels and subsequent incidence of hypertension in
      140 African Americans and 237 whites who were initially screened for possible
      participation in the Trials of Hypertension Prevention, phase 1. Plasma insulin
      and serum glucose were measured at baseline and at a follow-up examination 7
      years later. Blood pressure was measured by trained observers using a random-zero
      sphygmomanometer. Incident hypertension was defined as an average systolic
      pressure of 160 mm Hg or higher and/or diastolic pressure of 95 mm Hg or higher
      at a single visit and/or use of antihypertensive medication during follow-up.
      RESULTS: Over the 7 years of follow-up, the incidence of hypertension was 25.7%
      in the African Americans and 25.3% in the whites. Baseline plasma insulin and
      insulin-to-glucose ratio were associated with an increased risk of hypertension
      in both the African Americans and the whites. After adjustment for age, sex,
      race, body mass, heart rate, and alcohol consumption at baseline as well as
      intervention assignment in the Trials of Hypertension Prevention, phase 1, a 1-SD
      (21 pmol/mmol) difference in baseline insulin-to-glucose ratio was associated
      with a 2.77 (95% confidence interval, 1.48-5.19) odds ratio of hypertension in
      the African Americans and a 1.69 (95% confidence interval, 1.08-2.64) odds ratio
      in the whites. CONCLUSION: These results suggest that higher plasma insulin
      levels are associated with an increased risk of hypertension in both African
      Americans and whites.

PMID- 10074960
TI  - Heart failure survival among older adults in the United States: a poor prognosis
      for an emerging epidemic in the Medicare population.
AB  - OBJECTIVE: To describe the 6-year probability of survival for older adults after
      their first hospitalization for heart failure. SETTING: National Medicare
      hospital claims records for 1984 through 1986 and Medicare enrollment records
      from 1986 through 1992. DESIGN: We identified a national cohort of 170 239 (9%
      black patients) Medicare patients, 67 years or older, with no evidence of heart
      failure in 1984 or 1985, who were hospitalized and discharged for the first time
      in 1986 with a principal diagnosis of heart failure. For groups defined by race,
      sex, age, Medicaid eligibility, and comorbid conditions, we compared the
      probability of survival with Cox proportional hazards regression. RESULTS: Only
      19% of black men, 16% of white men, 25% of black women, and 23% of white women
      survived 6 years. One third died within the first year. Men had lower median
      survival and 38% greater risk of mortality than did women (P<.05). White men had
      10% greater risk of mortality than did black men (P<.05). Medicaid eligibility
      (white adults only) and diabetes were associated with increased mortality
      (P<.05). CONCLUSIONS: The prognosis for older adults with heart failure
      underscores the importance of prevention strategies and early detection and
      treatment modalities that can prevent, improve, or reverse myocardial
      dysfunction, particularly for the growing number of adults who are at increased
      risk for developing heart failure because of hypertension, diabetes, or
      myocardial infarction.

PMID- 10074961
TI  - The association of the combination of sumatriptan and methysergide in myocardial
      infarction in a premenopausal woman.
AB  - Acute myocardial infarction occurred in a 43 year-old premenopausal woman with
      controlled hypertension and no known coronary artery disease following the use of
      the antimigraine medications sumatriptan succinate injectable form and
      methysergide maleate. The use of sumatriptan is contraindicated within 24 hours
      of using ergotamine or ergotamine-type medications such as methysergide. This
      contraindication is based on the theoretical possibility of prolonged vasospasm
      with the combined use. Methysergide is primarily a serotonin type 2 (5-HT2)
      antagonist, although it does act as a partial agonist at 5-HT1 receptors. It is
      believed that a major component of coronary artery vasospasm is possibly due to 5
      HT supersensitivity mediated by 5-HT1Dbeta receptor activation. Drugs that
      selectively stimulate the 5-HT(D) receptors, such as sumatriptan, are potentially
      hazardous in people with underlying coronary artery disease, and agents with
      additional agonistic properties at these receptors may potentiate this effect.
      Physicians should be warned to inquire about prior 24-hour medication use before
      prescribing antimigraine medication.

PMID- 10074962
TI  - Using a cutoff of <10 ppm for breath hydrogen testing: a review of five years'
      experience.
AB  - To assess the clinical use of the breath hydrogen test in a large community
      hospital using a <10 ppm cutoff, we reviewed 222 tests performed over a 5-year
      period to evaluate patients for disaccharidase deficiency or bacterial overgrowth
      of the small intestine. Of these, the vast majority (195) were for lactose
      malabsorption, although fructose (17), sucrose (8) and lactulose (2) were also
      occasionally administered. One hundred eleven tests (50 percent) were positive,
      with an increase of at least 10 ppm hydrogen above the fasting level and a
      maximum value most commonly observed (42.3 percent of the time) at 3 hours post
      administration. Only 34 patients (15.3 percent) had symptoms noted during the
      test, as compared with 185 (83.3 percent) who had experienced persistent
      intestinal problems prior to the test. Recent conditions which may have caused
      intestinal distress, such as transient disaccharidase deficiency, infections,
      surgery or other disorders like Crohn's disease, ulcerative colitis or food
      poisoning, were recorded in only 14 cases. Patterns consistent with bacterial
      overgrowth of the small intestine were observed in only 3 cases. Of 111
      positives, 9 cases had increases between 10 and 20 ppm hydrogen and 7 showed the
      increase in the 3-hour sample, possibly reflecting a delayed transit through the
      intestine. Final diagnoses in 6 of these where information was available were for
      conditions other than malabsorption. We conclude that using a rise of 10 ppm to
      interpret a positive test does not contribute significantly to an increased
      frequency of false positives, but that patients with increases between 10 and 20
      ppm probably are not lactase deficient.

PMID- 10074963
TI  - Ontogeny of renal dysplasia in Ivemark syndrome: light and immunohistochemical
      characterization.
AB  - Ivemark syndrome is a rare sporadic or autosomal recessive disorder characterized
      by pancreatic fibrosis, renal dysplasia and hepatic dysgenesis. There have been
      no data describing the renal changes during embryologic development in this
      syndrome. In this report, we document the pathological findings of the kidney in
      three subjects with Ivemark syndrome: 6 months, 21 weeks and 16 weeks,
      respectively. Kidneys of subjects and age-matched controls were examined by light
      microscopy and immunohistochemically for cytokeratin, AE1/AE3 and epithelial
      membrane antigen. Renal dysplasia in Ivemark syndrome becomes apparent at 16
      weeks of gestation and progresses thereafter in severity. It is characterized by
      disturbance in glomerular differentiation, delay in tubular differentiation and
      abnormal expression of epithelial markers in glomeruli and tubules. Cytokeratin
      and epithelial membrane antigen expression of cysts is similar to that of the
      collecting ducts.

PMID- 10074964
TI  - Cardiac markers: from enzymes to proteins, diagnosis to prognosis, laboratory to
      bedside.
AB  - For many years, serologic markers have been used to assist cardiologists in the
      diagnosis and management of patients with cardiovascular diseases. The use of
      laboratory markers has evolved and kept pace with the field of cardiology itself.
      The early markers involved testing for total enzyme activity such as aspartate
      aminotransferase, lactate dehydrogenase and creatine kinase. Shortly thereafter,
      the World Health Organization included serial enzyme markers as part of the triad
      for diagnosis of acute myocardial infarction (AMI). It was soon recognized that
      isoenzymes such as for CK-MB and LD-1 provided more specific organ specificity.
      The need for reporting rapid results led to the development of totally automated
      isoenzyme assays, which have evolved from immunoinhibition (INH) techniques to
      mass assays. The current emphasis for cardiac markers is use of protein markers
      such as cardiac troponin T (cTnT) and I (cTnI). These markers are more sensitive
      and specific than isoenzyme markers and enable risk stratification for non-AMI
      patients with unstable angina: patients with high troponin have a higher risk for
      AMI and cardiac death within the immediate future (4 to 6 weeks). Prospective
      management of cardiac patients requires more rapid testing and reporting of
      results. Point-of-care testing platforms on whole blood are now available for
      emergency testing at bedside.

PMID- 10074965
TI  - Genetic determinants of trace element metabolism.

PMID- 10074966
TI  - Type 2 diabetes: the epidemic of the new millennium.
AB  - The increasing prevalence of obesity, which has reached epidemic proportions,
      raises the likelihood that a similar increase in diabetes will follow. Linkage
      between the two conditions is clear. Overweight is not only an important risk
      factor for the development of diabetes, but also has a significant impact on
      progression and complications. Diagnostic criteria for the recognition of
      diabetes and for monitoring of the disease process will become increasingly
      important. The role of laboratory evaluation needs to be reassessed in light of
      new concepts regarding classification and diagnostic criteria. The relative
      utility of glucose and glycosylated protein measurements should be addressed,
      particularly the relationship between laboratory findings and clinical
      guidelines. Blood glucose monitoring depends on establishment of the threshold
      for diagnosis. Additional issues are bedside monitoring, the goal of noninvasive
      glucose sensors and targeting of therapy. The laboratory scientist is likely to
      play a key role in the application of advances in the detection and management of
      diabetes.

PMID- 10074967
TI  - The integration of molecular diagnostic methods into the clinical laboratory.
AB  - Since the advent of the polymerase chain reaction in the mid-1980s, molecular
      diagnosis has become an important component of the services offered by many
      clinical laboratories. This presentation reviews selected applications of
      molecular methods in various sections and specialties of the clinical laboratory,
      and assesses the intellectual and technical qualifications and resources that
      traditional clinical laboratories can bring, and are bringing, to performance of
      molecular diagnostic tests. Special requirements for performance of molecular
      assays, in terms of both technical matters and clinical approaches, are also
      considered. Finally, attention is given to several contemporary factors that are
      tending to slow growth of molecular diagnosis in the clinical laboratory, and to
      other factors that are having a contrary effect, tending to promote growth in
      this area. A decision by an individual laboratory concerning the extent of its
      participation in molecular diagnosis should be based on recognition of the
      essential requirements for satisfactory performance of molecular testing, and a
      realistic appraisal of the laboratory's ability to meet these requirements.

PMID- 10074968
TI  - Primary subcutaneous mucormycosis (zygomycosis): a case report.
AB  - A case of mycormycosis presenting primarily as a subcutaneous mass of the left
      leg in an immunocompetent individual is described. The mass that was diagnosed
      initially as a non-specific foreign body granulomatous process recurred a year
      later. Histopathological examination of the primary and recurrent lesions
      revealed partly degenerated hyphae associated with acute necrotizing and chronic
      granulomatous inflammation. Histomorphological features of primary subcutaneous
      mucormycosis without predisposing factors have not been previously reported.

PMID- 10074969
TI  - The molecular pathology laboratory of the 21st century.
AB  - Human cells contain deoxyribonucleic acid in mitochondria and nuclei. Human
      diseases may be caused by mutations in mitochondrial DNA, nuclear DNA or both.
      The volume of work performed in the diagnostic molecular pathology laboratory
      will continue to grow as more disease-related mutations are discovered. Many
      factors will influence the diagnostic molecular pathology laboratory in the 21st
      century, such as future clinical laboratory organization, amplification methods,
      specimen integrity, ethical guidelines and opportunities to expand service. In
      the evaluation of a patient suspected of a mitochondrial DNA mutation, care must
      be exercised in the selection of a primer for amplification and of the specimen
      to be examined for the mutation. The uneven distribution of normal and abnormal
      mitochondrial DNA within the various tissues (heteroplasmy) may result in a
      normal mitochondrial DNA sequence if the wrong tissue is examined. The presence
      of mitochondrial-like sequences (pseudogenes) within nuclear DNA may result in
      amplification of nuclear genes if generic primers are used to duplicate a
      mitochondrial DNA gene. Diabetes mellitus is a heterogeneous disease with
      mutations occurring in a variety of proteins leading to either prereceptor,
      receptor or postreceptor defects. In this example, the diagnostic molecular
      pathology laboratory may be asked to define the specific genotype a specific
      patient with this common phenotype may possess.

PMID- 10074970
TI  - Intra-abdominal desmoplastic small round cell tumor: immunohistochemical evidence
      for up-regulation of autocrine and paracrine growth factors.
AB  - Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors
      typically involving the serosal surfaces of the peritoneum. Patients often
      present with abdominal pain, an abdominal mass, ascites or signs of intestinal
      obstruction. Cytogenetic and molecular studies have identified a characteristic
      t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product
      apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc
      finger DNA-binding domain of the WT1 gene. This product could lead to loss of the
      tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven
      expression of growth factors normally repressed by WT1. We investigated this
      latter possibility by performing immunohistochemical studies on formalin fixed
      tissue from 10 cases of DSRCT and five Wilms' tumors using antibodies to insulin
      like growth factor (IGF)-II, the latency associated peptide of transforming
      growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AB chain and
      PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive
      for these growth factors in DSRCT, while stromal cells were negative for IGF-II
      and positive for the other growth factors in parallel with the tumor cells.
      Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for
      IGF-II, and the latency associated peptide of TGF-beta1 and variably positive for
      PDGF-alpha receptor. These findings support the proposed molecular mechanism of
      tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.

PMID- 10074971
TI  - Active-phase labor arrest: oxytocin augmentation for at least 4 hours.
AB  - OBJECTIVE: To assess a labor-management protocol that mandated at least 4 hours
      of oxytocin augmentation before cesarean delivery for active-phase labor arrest.
      METHODS: We prospectively evaluated term gravidas in spontaneous labor with
      active-phase labor arrest (cervix at least 4 cm dilated and 1 cm or less of
      cervical progress in 2 hours). Exclusion criteria included nonvertex
      presentation, previous cesarean, multiple gestation, and a nonreassuring fetal
      heart rate tracing or chorioamnionitis at the time of labor arrest. After the
      diagnosis of active-phase arrest, oxytocin was initiated with an intent to
      achieve a sustained uterine contraction pattern of greater than 200 Montevideo
      units. Cesarean delivery was not performed for labor arrest until at least 4
      hours of a sustained uterine contraction pattern of greater than 200 Montevideo
      units, or a minimum of 6 hours of oxytocin augmentation if this contraction
      pattern could not be achieved. RESULTS: Five hundred forty-two women were managed
      by the protocol, and 92% delivered vaginally. The subsequent vaginal delivery
      rate for parous women who had not progressed (1 cm of cervical dilation or less)
      despite 2 hours of oxytocin augmentation was 91%, and it was 74% for nulliparas.
      With no labor progress after 4 hours of oxytocin augmentation, the subsequent
      vaginal delivery rates were 88% for parous women and 56% for nulliparas. There
      were no severe maternal complications. One neonate had persistent fetal
      circulation and one had a positive blood culture, but both did well. CONCLUSION:
      Extending the minimum period of oxytocin augmentation for active-phase labor
      arrest from 2 to at least 4 hours was effective and safe.

PMID- 10074972
TI  - Station at onset of active labor in nulliparous patients and risk of cesarean
      delivery.
AB  - OBJECTIVE: To determine whether term nulliparas with an unengaged vertex
      presentation at onset of active labor have a higher risk for cesarean delivery.
      METHODS: A retrospective cohort of 1250 randomly chosen nulliparous patients at
      37-42 weeks' gestation who delivered between 1988 and 1989 were selected. Four
      hundred forty-seven patients were excluded because of nonvertex presentation,
      cesarean delivery before active phase of labor, multiple gestation, delivery at
      less than 37 weeks' or greater than 42 weeks' gestation, induction of labor, or
      missing charts. For the purpose of this study, active labor was defined as
      regular contractions with cervical dilatation of at least 3 cm. The station at
      onset of active labor was recorded. Engagement was considered to be at station 0
      or below. RESULTS: Of the 803 patients in the study group, 567 presented
      unengaged and 236 patients presented engaged. The cesarean rates differed
      significantly between the two groups: 14% of those unengaged compared with 5% of
      those engaged (chi2 = 11.9, P < .001). After adjusting for confounding variables,
      engagement at the time of onset of active labor was associated with lower risk of
      cesarean delivery (odds ratio .512, 95% confidence interval .285, .922).
      CONCLUSION: Eighty-six percent of nulliparas with an unengaged vertex at onset of
      active labor delivered vaginally. Engaged vertex at the onset of active labor was
      associated with a lower risk of cesarean delivery.

PMID- 10074973
TI  - Delivery after previous cesarean: a risk evaluation. Swiss Working Group of
      Obstetric and Gynecologic Institutions.
AB  - OBJECTIVE: To examine the risks of vaginal delivery after previous cesarean and
      to find criteria to help decide whether a trial of labor or an elective repeat
      cesarean should be preferred. METHODS: We evaluated 29,046 deliveries after
      previous cesarean registered in a pooled database of 457,825 deliveries used to
      assess quality control in gynecology and obstetrics departments in Switzerland.
      RESULTS: Among the 17,613 trial-of-labor cases logged (attempt rate 60.64%), the
      success rate was 73.73% (65.56% after inducing labor and 75.06% after the
      spontaneous onset of labor). The following complications were significantly more
      frequent in the previous-cesarean group: maternal febrile episodes (relative risk
      [RR] 2.77; 95% confidence interval [CI] 2.52, 3.05), thromboembolic events (RR
      2.81; CI 2.23, 3.55), bleeding due to placenta previa during pregnancy (RR 2.06;
      CI 1.70, 2.49), uterine rupture (92 cases; RR 42.18; CI 31.09, 57.24), and
      perinatal mortality (118 cases, including six associated with uterine rupture; RR
      1.33; CI 1.10, 1.62). The postcesarean group also showed a 0.28% rate of
      peripartum hysterectomy (81 cases; RR 6.07; CI 4.71, 7.83). There was one
      maternal death in the group, compared with 14 maternal deaths in the group
      without previous cesarean (no statistical significance). The risk of uterine
      rupture for patients with previous cesareans was elevated in the trial-of-labor
      group compared with the group without trial of labor (RR 2.07; CI 1.29, 3.30),
      but all other maternal risks, including peripartum hysterectomy (RR 0.36; CI
      0.23, 0.56), were lower. When comparing the women having a trial of labor, the 70
      with uterine rupture more often had induced labor (24.29% compared with 13.92% in
      the nonrupture group; P = .013), had epidural anesthesia (24.29% compared with
      8.44%; P < .001), had an abnormal fetal heart rate tracing (32.86% compared with
      8.53%; P < .001), and had failure to progress (21.43% compared with 7.98%; P =
      .001). CONCLUSION: A history of cesarean delivery significantly elevates the
      risks for mother and child in future deliveries. Nonetheless, a trial of labor
      after previous cesarean is safe. Induction of labor, epidural anesthesia, failure
      to progress, and abnormal fetal heart rate pattern are all associated with
      failure of a trial of labor and uterine rupture.

PMID- 10074974
TI  - Pediatrician attendance at cesarean delivery: necessary or not?
AB  - OBJECTIVE: To determine whether it is necessary for a pediatrician to attend all
      cesarean deliveries. METHODS: We analyzed a database of 17,867 consecutive
      deliveries to determine the rates of low Apgar scores in the following three
      groups of patients: those with vaginal delivery, cesarean delivery using regional
      anesthesia without fetal indication, and cesarean delivery for fetal indications
      or using general anesthesia. RESULTS: There was a significantly higher rate of
      low Apgar scores in the fetal indications or general anesthesia group when
      compared with vaginal deliveries. Specifically, 35 (5.8%) of 596 cesareans for
      fetal heart rate abnormality or using general anesthesia had 1-minute Apgars
      under 4 in contrast to 115 of 10,270 (1.1%) of vaginal deliveries. There was no
      significantly increased risk for low Apgar scores in the group of cesareans using
      regional anesthesia for nonfetal indications (33 of 2057, 1.6%). Results were
      similar for Apgar scores under 7 at 5 minutes. CONCLUSION: Because there is no
      higher incidence of low Apgar scores in cesarean deliveries using regional
      anesthesia for nonfetal indications compared with vaginal deliveries, there is no
      convincing need for pediatrician attendance at such deliveries.

PMID- 10074975
TI  - Epidural analgesia and intrapartum fever: placental findings.
AB  - OBJECTIVE: To assess whether epidural analgesia is associated with fever,
      independent of maternal infection, by evaluating the relationship between
      epidural analgesia and inflammation of the placenta. METHODS: Placentas collected
      prospectively from women with singleton gestations, who delivered 6 hours or more
      after membrane rupture, were evaluated systematically for histologic inflammation
      by an investigator blinded to all clinical information. Maternal and neonatal
      markers of infection were assessed in the cohorts who did and did not receive
      epidural analgesia. RESULTS: One hundred forty-nine consecutive placentas were
      analyzed, and 80 (54%) of these women received epidural analgesia. On univariate
      analysis, significant differences between epidural and no epidural groups were
      found with respect to maternal fever 38C or greater (46% versus 26%, P = .01),
      placenta inflammation (61% versus 36%, P = .002), and length of labor (11.8 hours
      versus 9.6 hours, P = .03). The combination of maternal fever plus placental
      inflammation was significantly more common in the epidural group (35% versus 17%
      P = .02). However, maternal fever in the absence of supporting evidence of
      infection, in the form of placental inflammation, was not increased after
      epidural analgesia (11% versus 9%, P = .61). CONCLUSION: Epidural analgesia is
      associated with intrapartum fever, but only in the presence of placental
      inflammation. This suggests that the fever reported with epidural analgesia is
      due to infection rather than the analgesia itself.

PMID- 10074976
TI  - The effect of spinal anesthesia on the success rate of external cephalic version:
      a randomized trial.
AB  - OBJECTIVE: To identify the effect of spinal anesthesia on the success rate of
      external cephalic version after 36 weeks' gestation. METHODS: Women with
      singleton breech presentations after 36 weeks' gestation were offered enrollment.
      Those who agreed were randomized to receive spinal anesthesia or no anesthesia.
      Up to four attempts were made using ultrasound surveillance. External cephalic
      version was terminated with patient discomfort or fetal heart decelerations.
      Statistical analysis based on intent-to-treat was performed using chi2, Student t
      tests, and multivariate analysis. Sample size projection based on 20% difference
      in success rate from a baseline of 50% indicated a need for 50 women in each
      group. RESULTS: One hundred two women were entered in the study from October 1993
      to August 1997. There were no differences between groups in parity, maternal age,
      amniotic fluid index, gestational age, birth weight, placental location, type of
      breech presentation, maternal weight, or gestational age at delivery. Forty-four
      external cephalic versions were successful. Fifty (49%) women received spinal
      anesthesia, and 52 (51%) did not; there was no difference in the overall success
      rate between groups (44% spinal versus 42% no spinal). Spontaneous version
      occurred before external cephalic version was attempted in four patients in the
      spinal group (after the spinal was given) and one patient in the no-spinal group.
      These patients were included in the analysis. CONCLUSION: Spinal anesthesia does
      not increase the external cephalic version success rate in singleton pregnancies
      with breech presentations after 36 weeks' gestation.

PMID- 10074977
TI  - Plain and buffered lidocaine for neonatal circumcision.
AB  - OBJECTIVE: To determine if buffered lidocaine provided a more effective nerve
      block in a short time than plain lidocaine for neonatal circumcision. METHODS:
      One hundred ninety-four newborn males were studied in a randomized trial using
      two dorsal penile nerve block preparations for circumcision. Ninety-two received
      plain lidocaine, and 102 received buffered lidocaine. The infants were evaluated
      at timed intervals before the procedure, during anesthetic injection, and during
      circumcision. Objective measurements of heart rate and oxygen saturation, and
      subjective determinations of behavioral state were recorded. Using heart rate as
      the major outcome variable, it was determined that 65 subjects per group would be
      needed to achieve a power of .08. Complications also were noted. RESULTS: Heart
      rates and oxygen saturations were similar in the two groups at each timed
      interval. The behavioral characteristics and amount of crying also were
      comparable in both groups. The only complication was minor bleeding, seen in each
      group. CONCLUSION: Adding a buffering agent to lidocaine did not provide a more
      effective level of anesthesia in a short time.

PMID- 10074978
TI  - Cytology alone versus cytology and cervicography for cervical and cervicography
      for cervical cancer screening: a randomized study. European Society for
      Oncological Research.
AB  - OBJECTIVE: To compare the ability of combined cytology and cervicography with
      cytology alone to decrease the number of premalignant cervical lesions found in
      subsequent screening. METHODS: Five thousand five hundred fifty women 18-91 years
      old were randomized to cytology plus cervicography or cytology alone. One year
      later, women were rescreened using both cytology and cervicography. All women
      with positive lesions were referred for colposcopically directed biopsies and
      treatment as indicated. We expected to decrease by half the number of cervical
      intraepithelial neoplasia (CIN) lesions at 1-year screening by adding
      cervicography to cytology at initial screening. RESULTS: Compared with cytology
      screening alone, screening with cytology plus cervicography showed a 30%
      reduction in CIN I-II-III cervical lesions at 1-year screening round (relative
      risk [RR] 0.70; 95% confidence interval [CI] 0.32, 1.55, P = .35) and a 43%
      reduction in CIN II-III cervical lesions (RR 0.57; Cl 0.14, 2.16, P = .36). Most
      lesions detected by one test were not detected by the other. In a retrospective
      search, nine biopsies (one normal and eight revealing CIN I or more on
      histopathology) were found to be positive for the human papillomavirus; five of
      the nine biopsies were found by cytology, three by cervicography, and one by both
      tests. CONCLUSION: The addition of cervicography to cytology in initial screening
      did not significantly decrease the number of premalignant cervical lesions
      detected 1 year later, probably because of the transient nature of most of these
      lesions. Because cytology and cervicography seemed to detect different
      premalignant lesions, it is possible that cervicography could detect lesions that
      do not express the cellular abnormalities necessary for detection by cytology.

PMID- 10074979
TI  - Postpartum regression rates of antepartum cervical intraepithelial neoplasia II
      and III lesions.
AB  - OBJECTIVE: To study the histologic regression and progression rates of cervical
      intraepithelial neoplasia (CIN) II and III after delivery and the effect the
      route of delivery has on the regression rates of CIN. METHODS: Pregnant patients
      with satisfactory colposcopic examinations and biopsy-proven CIN II and III were
      identified. Delivery information and postpartum biopsy results were obtained by
      chart review. RESULTS: Two hundred seventy-nine patients had antepartum biopsies
      of CIN II or CIN III. Of these, 126 women were excluded for the following
      reasons: lost to follow-up (75), human immunodeficiency virus positive (two),
      cesarean hysterectomy (four), and inadequate postpartum follow-up (45). This
      yielded a study group of 153 patients consisting of 82 with CIN II and 71 with
      CIN III. The regression rates were 68% and 70% among CIN II and CIN III patients
      (P = .78), respectively. Seven percent of patients with CIN II progressed to CIN
      III on postpartum evaluation. Twenty-five percent of those patients with CIN II
      and 30% of those with CIN III remained the same postpartum. No CIN lesions
      progressed to invasive carcinoma. There were no differences in regression rates
      or progression rates among the women who had vaginal deliveries (130), women who
      labored and then underwent cesarean (17), or women who proceeded to a cesarean
      without laboring (six). CONCLUSION: We found similar high postpartum regression
      rates despite the route of delivery. We recommend conservative antepartum
      management with postpartum colposcopic evaluation regardless of route of delivery
      because we are unable to predict which of these lesions are more likely to
      regress.

PMID- 10074980
TI  - Transvaginal endometrial sonography in postmenopausal women taking tamoxifen.
AB  - OBJECTIVE: To evaluate sonographic measurements of endometrial thickness in
      postmenopausal women taking adjuvant tamoxifen therapy for breast cancer, and to
      correlate sonographic and pathologic findings to symptoms and duration of
      tamoxifen therapy. METHODS: Medical records and sonograms of 80 postmenopausal
      women treated for breast cancer with adjuvant tamoxifen therapy were reviewed
      retrospectively. Endometrial thickness was recorded as a single-layer thickness
      and considered abnormal when greater than 2.5 mm for postmenopausal women.
      Sonographic endometrial thickness was correlated to histologic findings,
      symptoms, and duration of tamoxifen therapy. RESULTS: Fifty-seven of 80
      postmenopausal women (69%) had single-layer endometrial thicknesses of 2.5 mm or
      greater, measured by transvaginal sonography, and 55 of 57 had endometrial
      biopsies or dilatations and curettage. Biopsies detected 24 cases of abnormal
      endometria, including endometrial carcinoma (two), breast carcinoma metastatic to
      the endometrium (one), endometrial polyps (13), tubal metaplasia (three), and
      benign endometrial hyperplasia (five). Using a single-layer endometrial thickness
      greater than 2.5 mm by transvaginal ultrasound, 21 of 24 (87.5%) women with
      abnormal endometria were detected. Women with abnormal pathologic findings had a
      significantly thicker mean single-layer endometrial thickness than those with
      normal findings, 7 mm versus 4 mm (P < .01). Twelve women had postmenopausal
      bleeding, all of whom had a single-layer endometrial thickness greater than 2.5
      mm on transvaginal sonography. CONCLUSION: With a sensitivity of detecting
      endometrial abnormalities of 84%, transvaginal sonography was useful for studying
      postmenopausal tamoxifen-treated women.

PMID- 10074981
TI  - Prognostic significance of tumor angiogenesis in endometrial cancer.
AB  - OBJECTIVE: To determine the prognostic effect of intratumor microvessel density
      in a series of unselected patients with endometrial carcinoma. METHODS: We
      reviewed 93 consecutive patients treated surgically for endometrial cancer at the
      University Hospital of Vienna between 1983 and 1989. Histologic sections were
      obtained from original paraffin-embedded blocks and stained immunohistochemically
      for CD34 antigen. Microvessel density was determined by enumeration of intratumor
      CD34-positive cells under a light microscope at 200 x magnification using an
      examination area of 0.74 mm2. Log-rank test and Cox proportional-hazards models
      (univariate and multivariate) were applied for overall survival analysis.
      RESULTS: Overall, the 25% quantile of survival was reached at 37.9 months. The 5
      year survival rate was 82.2% in 69 patients whose tumors had microvessel counts
      no more than 100/0.74 mm2 field, and 52.0% in 24 patients whose tumors had
      microvessel counts of more than 100/0.74 mm2 field (log-rank P = .004). In the
      multiple Cox model, high microvessel counts (relative risk [RR] 1.2; 95%
      confidence interval [CI] 1.1, 1.4) as well as undifferentiated tumors (RR 6.1; CI
      2.2, 16.8), and advanced stage of disease (RR 2.6; CI 1.3, 5.1) independently
      exerted an adverse influence on the survival of patients with endometrial cancer.
      CONCLUSION: High intratumor microvessel count is associated with poor survival of
      patients with endometrial cancer.

PMID- 10074982
TI  - Perineal talc exposure and subsequent epithelial ovarian cancer: a case-control
      study.
AB  - OBJECTIVE: To evaluate the role of talcum powder use as a risk factor for the
      development of epithelial ovarian cancer. METHODS: In a case-control study, 499
      patients with epithelial ovarian cancer were frequency matched for age at
      diagnosis (-5 years) with a control population of 755 patients. The odds ratio
      (OR) for the development of epithelial ovarian cancer was estimated using
      logistic regression analysis with adjustment for age at diagnosis, parity, oral
      contraceptive use, smoking history, family history of epithelial ovarian cancer,
      age at menarche, menopausal status, income, education, geographic location,
      history of tubal ligation, and previous hysterectomy. RESULTS: Two hundred twenty
      one of 462 patients (47.8%) in the study population and 311 of 693 patients
      (44.9%) in the control population had ever used talcum powder (OR 0.92; 95%
      confidence interval [CI] 0.24, 3.62). A significant association between duration
      of talc use and development of epithelial ovarian cancer was not demonstrable for
      1-9 years (OR 0.9; 95% CI 0.6, 1.5), for 10-19 years (OR 1.4; 95% CI 0.9, 2.2),
      or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible
      confounding variable of surgery for the management of ovarian cancer, we omitted
      135 patients in the study population who underwent hysterectomy within 5 years of
      the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation
      or hysterectomy among talc users still failed to demonstrate an increased risk
      for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). CONCLUSION: A
      significant association between the use of talcum powder and the risk of
      developing epithelial ovarian cancer is not demonstrable, even with prolonged
      exposure.

PMID- 10074983
TI  - Pseudocyst of the umbilical cord: prenatal sonographic appearance and clinical
      significance.
AB  - OBJECTIVE: To assess the clinical significance of umbilical cord pseudocysts
      detected prenatally by sonography. METHODS: The prenatal sonographic findings,
      karyotype, and perinatal outcome in 13 fetuses with umbilical cord pseudocysts
      were reviewed retrospectively. RESULTS: Umbilical cord pseudocysts were diagnosed
      at a median gestation of 27 weeks (range 15-37). Pseudocysts were single in eight
      cases with cyst diameters ranging from 20 to 50 mm, and double in one case. In
      the remaining four cases, multiple small cystic masses measuring less than 8 mm
      were identified. Additional sonographic findings were noted in 11 cases; ten of
      these fetuses had prenatal karyotyping, which showed trisomy 18 in five cases,
      trisomy 13 in one case, and a 46,XX, inv ins(18;21) complement in one case. Among
      the seven chromosomally abnormal fetuses, umbilical cord pseudocysts were
      multiple in four fetuses and single in three. All chromosomally abnormal fetuses
      and two euploid fetuses with associated structural defects died in utero or in
      the neonatal period. There were no perinatal complications in either of the
      fetuses with isolated pseudocysts. CONCLUSION: The prenatal sonographic
      appearance of umbilical cord pseudocysts varied widely. These umbilical cord
      cystic masses were associated strongly with chromosomal disorders and structural
      defects, regardless of their sonographic appearance in utero.

PMID- 10074984
TI  - Objective diagnosis of micrognathia in the fetus: the jaw index.
AB  - OBJECTIVE: To provide an objective and accurate tool to diagnose micrognathia in
      the fetus. METHODS: The anteroposterior and laterolateral diameter of the
      mandible were measured in 262 normal fetuses between 12 and 37 weeks' gestation
      and plotted against gestational age and biparietal diameter (BPD). The jaw index
      (anteroposterior mandibular diameter/BPD x 100) was then tested against the usual
      subjective method for diagnosing micrognathia, consisting of the evaluation of
      the facial profile, in a population of 198 malformed fetuses, 11 of which had
      micrognathia at necropsy or birth. RESULTS: The mandibular growth was linearly
      correlated with gestational age and BPD. Using a cutoff level of less than 23,
      the jaw index had a 100% sensitivity and 98.1% specificity in diagnosing
      micrognathia, in comparison with 72.7% and 99.2% shown by the subjective
      evaluation of the fetal profile. With a cutoff of 21, it yielded a positive
      predictive value of 100%. CONCLUSION: We demonstrated the linear relationship
      between mandibular growth and gestational age or BPD. In addition, we validated
      the jaw index as an objective tool for diagnosis of micrognathia in the fetus.

PMID- 10074985
TI  - Amniotic fluid lamellar body count: cost-effective screening for fetal lung
      maturity.
AB  - OBJECTIVE: To create a highly specific cascade testing scheme for fetal lung
      maturity using the lamellar body count, lecithin/sphingomyelin ratio (L/S), and
      phosphatidylglycerol. METHODS: A nondedicated hematology analyzer (Sysmex NE
      1500, Toa Medical Electronics, Los Angeles, CA) was used to determine the
      lamellar body counts of 209 unspun amniotic fluid specimens. Maximally specific
      lamellar body count cutoffs for biochemical maturity and immaturity were
      determined using receiver operating characteristic curves. Biochemical lung
      maturity was defined as either a mature L/S ratio or phosphatidylglycerol.
      Biochemical lung immaturity was defined as both an immature L/S ratio and an
      immature phosphatidylglycerol. RESULTS: A lamellar body count of less than 8000
      (n = 17) was 100% specific for biochemical lung immaturity (positive predictive
      value = 100%, negative predictive value = 86%). A lamellar body count of greater
      than 32,000 was 98% specific for biochemical lung maturity (positive predictive
      value = 99%, negative predictive value = 63%). CONCLUSION: Testing only specimens
      where the lamellar body count was greater than 8000 and less than or equal to
      32,000 for the L/S ratio and phosphatidylglycerol would preclude the need for 76%
      of all L/S and phosphatidylglycerol assays. Because the lamellar body count is
      quick, simple, and universally available, it could serve as an extremely cost
      effective screening test for fetal lung maturity.

PMID- 10074986
TI  - Congenital malformations after the use of inhaled budesonide in early pregnancy.
AB  - OBJECTIVE: To study possible teratogenic risks with the use of an inhaled
      glucocorticoid, budesonide, in early pregnancy. METHODS: Using the Swedish
      Medical Birth Registry, congenital malformations were studied in 2014 infants
      whose mothers had used inhaled budesonide for asthma in early pregnancy. The
      presence of congenital malformations was checked further with auxiliary
      registries. RESULTS: No increase in the general rate of congenital malformations
      was observed: 3.8% (95% confidence interval [CI] 2.9, 4.6) of the infants had a
      congenital malformation diagnosed, which is similar to the population rate
      (3.5%). After exposure to budesonide, four infants were born with orofacial
      clefts; this also is similar to the expected number (3.3). CONCLUSION: Even
      though a specific teratogenic effect of use of budesonide in early pregnancy
      cannot be ruled out, it is unlikely that a clinically significant teratogenic
      risk exists.

PMID- 10074987
TI  - Maternal magnesium sulfate and the development of neonatal periventricular
      leucomalacia and intraventricular hemorrhage.
AB  - OBJECTIVE: Neonatal periventricular leucomalacia and intraventricular hemorrhage
      are strong correlates of cerebral palsy. Our objective was to evaluate the effect
      of maternal magnesium sulfate exposure on the incidence and severity of
      periventricular leucomalacia and intraventricular hemorrhage in preterm neonates.
      METHODS: Nine hundred eighteen consecutive inborn neonates with birth weights
      from 500 to 1750 g were divided primarily into two groups on the basis of
      maternal exposure to magnesium sulfate. The groups were divided secondarily into
      two clinical groups, a physician-initiated group, which consisted of neonates
      delivered for maternal or fetal indications, and a preterm delivery group, which
      included neonates delivered as a result of preterm labor or preterm premature
      rupture of membranes. These clinical groups were stratified further into
      magnesium sulfate-exposed and -unexposed subgroups. Neonatal neurosonograms were
      performed on days 3 and 7 of life and described as normal or abnormal. Abnormal
      sonograms included any periventricular leucomalacia or intraventricular
      hemorrhage. Severe lesions included periventricular leucomalacia, periventricular
      leucomalacia with intraventricular hemorrhage, or grades 3 or 4 intraventricular
      hemorrhage. The magnesium sulfate groups and the clinical groups with their
      magnesium sulfate strata were compared for the incidence and severity of abnormal
      sonograms. They also were compared for maternal and neonatal characteristics.
      RESULTS: Maternal magnesium sulfate exposure was not associated with reduction in
      the incidence of abnormal sonograms when compared with the unexposed group (27%
      compared with 33%, P = .06). However, fewer severe lesions were observed in the
      exposed group (14% compared with 21%, P = .004). When clinical groups were
      examined, magnesium sulfate was not associated with a decrease in abnormal
      sonograms (adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.78,
      1.52, P = .40) or severe lesions (adjusted OR 1.11, 95% CI 0.73, 1.68, P = .42).
      Logistic regression analyses of magnesium sulfate exposure within clinical groups
      controlling for the confounding effects of maternal and neonatal characteristics
      revealed no protective effect of magnesium sulfate exposure on the incidence of
      abnormal sonograms (adjusted OR 1.01, 95% CI 0.70, 1.44, P = .97) or severe
      lesions (adjusted OR 1.01, 95% CI 0.70, 1.74, P = .69). Within clinical groups,
      the preterm delivery group exhibited an increased risk for abnormal sonograms
      (adjusted OR 1.63, 95% CI 1.01, 2.67, P = .05) and severe lesions (adjusted OR
      9.79, 95% CI 3.27, 29.29, P = .001) when compared with the physician-initiated
      delivery group, independent of maternal magnesium sulfate exposure. CONCLUSION:
      Maternal magnesium sulfate exposure had no protective effect on the incidence or
      severity of periventricular leucomalacia and intraventricular hemorrhage in
      preterm neonates. The prevalence of these lesions was correlated better with the
      clinical group of origin and indication for its use.

PMID- 10074988
TI  - Nucleated red blood cells in infants of smoking mothers.
AB  - OBJECTIVE: To evaluate whether the absolute nucleated red blood cell (RBC) count
      is elevated in term, appropriate for gestational age (AGA) infants born to
      smoking women. METHODS: We compared absolute nucleated RBC counts taken during
      the first 12 hours of life in two groups of term, vaginally delivered, AGA
      infants, one group born to mothers who smoked during pregnancy (n = 30) and the
      other born to mothers who did not smoke (n = 30). We excluded infants of women
      with diabetes, hypertension, or alcohol or drug abuse, and infants with heart
      rate abnormalities, hemolysis, blood loss, or chromosomal anomalies. RESULTS:
      There were no differences between the groups in birth weight, gestational age,
      maternal age, gravidity, parity, maternal analgesia during labor, 1- and 5-minute
      Apgar scores, corrected white blood cell counts, lymphocyte counts, or
      hematocrits. The median absolute nucleated RBC count in infants of smoking
      mothers was 0.5 x 10(9)/L (range 0 to 5.0) versus 0.0005 x 10(9)/L (range 0 to
      0.6) in nonsmoking controls (P < .002). Regression analysis that included Apgar
      scores, gestational age, and number of cigarettes smoked per day showed a
      significant correlation of absolute nucleated RBC count only with the number of
      cigarettes smoked per day (P < .001). CONCLUSION: At birth, term AGA infants born
      to smoking mothers have increased circulating absolute nucleated RBC counts
      compared with controls. The absolute nucleated RBC count in newborns correlates
      with the number of cigarettes smoked during pregnancy.

PMID- 10074989
TI  - Effect of a vaginal device on quality of life with urinary stress incontinence.
AB  - OBJECTIVE: To assess the effect of a vaginal device (Continence Guard) on urine
      leakage and quality of life. METHODS: Fifty-five women with stress incontinence
      participated in a 3-month study. They were assessed by the Incontinence Impact
      Questionnaire, two incontinence-related quality-of-life questions, a generic
      quality-of-life questionnaire (Short Form-36), two 24-hour home pad weighing
      tests, a 2-day voiding diary, uroflowmetry, urine cultures, and a questionnaire
      about subjective effectiveness of the device. RESULTS: Forty-one (74.5%) women
      completed the study. Estimated on an intent-to-treat basis, the vaginal device
      was associated with subjective cure in 11 women (20%) and improvement in 27
      (49%). The mean 24-hour pad test leakage and leakage episodes in the voiding
      diary decreased significantly. Fifty-eight percent of the 55 women enrolled
      wanted to continue using the device after 3 months. The quality of life measured
      by the Incontinence Impact Questionnaire showed highly significant improvement,
      and the results of the two incontinence-related quality of life questions also
      showed significant improvement. Responses to the Short Form-36 general health
      questionnaire showed no significant changes. Improvement on the Incontinence
      Impact Questionnaire correlated with improvements in incontinence, whereas the
      Short Form-36 scores were unchanged. CONCLUSION: Treatment with the Continence
      Guard significantly decreases leakage and improves quality of life in women with
      symptoms of urinary stress incontinence. An incontinence-specific, rather than a
      generic, quality-of-life questionnaire was important in assessing treatment
      outcomes.

PMID- 10074990
TI  - Sonographic evaluation of the bladder neck in continent and stress-incontinent
      women.
AB  - OBJECTIVE: To evaluate a new sonographic method to measure depth and width of
      proximal urethral dilation during coughing and Valsalva maneuver and to report
      its use in a group of stress-incontinent and continent women. METHODS: Fifty
      eight women were evaluated, 30 with and 28 without stress incontinence proven
      urodynamically, with a bladder volume of 300 mL and the subjects upright.
      Urethral pressure profiles at rest were performed with a 10 French microtip
      pressure catheter. Bladder neck dilation and descent were assessed by perineal
      ultrasound (5 MHz curved linear array transducer) with the help of ultrasound
      contrast medium (galactose suspension-Echovist-300), whereas abdominal pressure
      was assessed with an intrarectal balloon catheter. Statistical analysis used the
      nonparametric Mann-Whitney test. RESULTS: The depth and diameter of urethral
      dilation could be measured in all women. During Valsalva, all 30 incontinent
      women exhibited urethral dilation. One incontinent woman showed dilation only
      while performing a Valsalva maneuver, not during coughing. In the continent
      group, 12 women presented dilation during Valsalva and six during coughing. In
      continent women, dilation was visible only in those who were parous. Nulliparous
      women did not have dilation during Valsalva or coughing. Bladder neck descent was
      visible in continent and incontinent women. CONCLUSION: This method permits
      quantification of depth and diameter of bladder neck dilation, showing that both
      incontinent and continent women might have bladder neck dilation and that urinary
      continence can be established at different locations along the urethra in
      different women. Parity seems to be a main prerequisite for a proximal urethral
      defect with bladder neck dilation.

PMID- 10074991
TI  - Helical computed tomography in differentiating appendicitis and acute gynecologic
      conditions.
AB  - OBJECTIVE: To determine the accuracy and effect of helical computed tomography
      (CT) in women clinically suspected of having either appendicitis or an acute
      gynecologic condition. METHODS: One hundred consecutive nonpregnant women
      suspected of having appendicitis or an acute gynecologic condition prospectively
      had helical CT. Interpretations were correlated with surgical and pathologic
      findings (41 cases) and clinical follow-up for at least 2 months (59 cases). The
      accuracy for confirming or excluding both appendicitis and acute gynecologic
      conditions was determined. The effect on patient care was determined by comparing
      pre-CT plans with actual treatment. RESULTS: Thirty-two women had appendicitis,
      15 had acute gynecologic conditions, 27 had other specific diagnoses, and 26 had
      nonspecific abdominal pain. For diagnosing appendicitis or acute gynecologic
      conditions, CT had 100% and 87% sensitivity, 97% and 100% specificity, 94% and
      100% positive predictive value, 100% and 98% negative predictive value, and 98%
      and 98% accuracy, respectively. After CT was done, 36 planned hospital
      admissions, 25 planned hospital observations, and six planned appendectomies were
      deferred; six women had alternative surgical procedures on the basis of CT
      results. One patient had an unnecessary appendectomy on the basis of CT findings.
      CONCLUSION: Helical CT is an excellent imaging option for differentiating
      appendicitis from most acute gynecologic conditions.

PMID- 10074992
TI  - Effects of providing hospital-based doulas in health maintenance organization
      hospitals.
AB  - OBJECTIVE: To evaluate whether providing doulas during hospital-based labor
      affects mode of delivery, epidural use, breast-feeding, and postpartum
      perceptions of the birth, self-esteem, and depression. METHODS: This was a
      randomized study of nullipara enrollees in a group-model health maintenance
      organization who delivered in one of three health maintenance organization
      managed hospitals; 149 had doulas, and 165 had usual care. Study data were
      obtained from the mothers' medical charts, study intake forms, and phone
      interviews conducted 4-6 weeks postpartum. RESULTS: Women who had doulas had
      significantly less epidural use (54.4% versus 66.1%, P < .05) than women in the
      usual-care group. They also were significantly (P < .05) more likely to rate the
      birth experience as good (82.5% versus 67.4%), to feel they coped very well with
      labor (46.8% versus 28.3%), and to feel labor had a very positive effect on their
      feelings as women (58.0% versus 43.7%) and perception of their bodies' strength
      and performance (58.0% versus 41.0%). The two groups did not differ significantly
      in rates of cesarean, vaginal, forceps, or vacuum delivery, oxytocin
      administration; or breast-feeding, nor did they differ on the postpartum
      depression or self-esteem measures. CONCLUSION: For this population and setting,
      labor support from doulas had a desirable effect on epidural use and women's
      perceptions of birth, but did not alter need for operative deliveries.

PMID- 10074993
TI  - Hemoglobin and red cell indices correlated with serum ferritin concentration in
      late pregnancy.
AB  - OBJECTIVE: To study the correlation between third-trimester serum ferritin
      concentration and hemoglobin and red cell indices to select the best hematologic
      characteristic to identify women who need iron therapy. METHODS: In a prospective
      study, blood was drawn from pregnant women with hemoglobin above 10 g/dL, and
      thalassemia trait excluded at booking, at 28-30 weeks' gestation to study the
      correlation (Spearman p value) between serum ferritin concentration and
      hemoglobin level, mean corpuscular volume, mean cell hemoglobin, mean cell
      hemoglobin concentration, and hematocrit. The best relationship was identified
      using receiver operating characteristic (ROC) curves. RESULTS: Serum ferritin
      concentration correlated significantly with hemoglobin (p = .211), mean
      corpuscular volume (p = .332), mean cell hemoglobin (p = .304), and hematocrit (p
      = .199). The area under the ROC curve was largest for hemoglobin. CONCLUSION:
      Serum ferritin concentration at the early third trimester correlated best with
      hemoglobin level. If a hemoglobin level of 11 g/dL or below (25% of all patients)
      was used as the cutoff, 64% of women who needed iron therapy were identified.

PMID- 10074994
TI  - Predicting delivery within 48 hours in women treated with parenteral tocolysis.
AB  - OBJECTIVE: To develop a prediction rule using clinical admission characteristics
      for women treated with parenteral tocolysis for preterm labor who are at highest
      risk of delivery within 48 hours. METHODS: We performed a case-control study of
      patients treated with magnesium sulfate for idiopathic preterm labor. A case was
      defined as a patient who received magnesium sulfate tocolysis and delivered
      within 48 hours of admission. We selected a 48-hour delay to delivery as a
      clinically relevant endpoint for the maximization of steroid benefit. Controls
      were patients who received magnesium sulfate tocolysis and remained undelivered
      48 hours after admission. Cases and controls were identified by merging a
      pharmacy billing database with International Classification of Disease codes for
      premature labor. Medical records were reviewed and risk factor information was
      obtained. We focused on risk factors within the first hour of admission, because
      our goal was to identify patients at high risk of delivery early in their
      hospital course. Backward stepwise logistic regression was used to develop
      explanatory and predictive models. The focus of the predictive model was to
      maximize the test's sensitivity and negative predictive value. RESULTS: We
      identified 50 cases and 150 controls. The following six variables were included
      in the initial multivariable models based on bivariate analyses: white blood cell
      count at least 14.0 (1000/microL), cervical dilation at least 2 cm, bleeding,
      substance abuse, parity, and previous abortion. A two-variable model containing
      cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of
      62%, and specificity of 76%, and it was as sensitive and specific as more complex
      models. CONCLUSION: Cervical dilation of at least 2 cm and bleeding on admission
      had an overall accuracy of 73% in predicting the likelihood of delivery within 48
      hours in women receiving magnesium sulfate.

PMID- 10074995
TI  - Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous
      immunoglobulin therapy.
AB  - OBJECTIVE: To assess maternal and fetal outcomes in 15 patients with
      antiphospholipid syndrome (19 pregnancies) treated with intravenous
      immunoglobulin (IV Ig) during pregnancy. METHODS: Monthly IV Ig therapy was
      initiated in the first or early second trimester of all pregnancies except two.
      Additional therapy consisted of low-dose aspirin and subcutaneous heparin. Six
      patients also received steroid therapy. Serial anticardiolipin IgG levels were
      measured in eight pregnancies. RESULTS: The live-birth rate was 84% (16 of 19
      live births), and there were three pregnancy losses. There were no cases of fetal
      growth restriction (FGR). Preeclampsia and nonreassuring fetal status were each
      diagnosed in 25% of the pregnancies. Seventy-five percent of the infants were
      delivered at 34 weeks' gestation or later. Anticardiolipin IgG decreased
      throughout the course of therapy in seven pregnancies. Placental pathology was
      minimal. CONCLUSION: Pregnancy complications appear to be minimized with the use
      of IV Ig. Definitive recommendations regarding the use of IV Ig in pregnancy
      await the conclusion of randomized trials. If the combination of IV Ig, aspirin,
      and heparin significantly decreases the incidences of FGR and prematurity, it may
      be a cost-effective primary therapy for pregnancies complicated by the
      antiphospholipid syndrome.

PMID- 10074996
TI  - Nitric oxide production with preeclampsia.
AB  - OBJECTIVE: To clarify production of nitric oxide with pre-eclampsia. METHODS:
      Production of nitric oxide and elimination of its metabolites, nitrite and
      nitrate, determines ultimately the level of those metabolites in plasma of
      subjects whose diets lack them. We measured simultaneously plasma levels and
      renal clearance of nitrite and nitrate in 20 women with preeclampsia and in 21
      healthy pregnant women. Fifteen preeclamptic gravidas were receiving
      antihypertensive medication and five received betamethasone 1-4 days before the
      study. Subjects were prescribed low nitrite and nitrate diets for 24 hours and
      fasted overnight before collection of plasma and urine samples. Nitrite and
      nitrate were measured spectrophotometrically by Griess reaction. RESULTS:
      Preeclamptic women had significantly higher plasma levels of nitrite and nitrate
      (18.1+/-6.2 micromol/L versus 13.0+/-4.3 micromol/L, mean+/-standard deviation
      [SD], P = .009), which because renal clearance did not differ (0.6+/-0.3 versus
      0.7+/-0.3 mL/s), indicated increased production of nitric oxide with preeclampsia
      that was unaffected by antihypertensives or betamethasone. The mean plasma level
      of endothelin-1 was increased (5.1+/-1.4 versus 3.6+/-1.0 pg/mL, P < .001), and
      urinary output of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin
      F1alpha was decreased (39.1+/-18.0 versus 61.3+/-35.6 ng/mmol creatinine, P =
      .019) with preeclampsia. These two endothelial markers showed no relation to
      plasma nitrite and nitrate. CONCLUSION: Nitric oxide production was increased
      with preeclampsia. The biologic significance of increased production is unknown,
      but it might be compensation for the vasoconstriction of preeclampsia.

PMID- 10074997
TI  - Ultrasound-assisted laparoscopic creation of a neovagina by modification of
      Vecchietti's operation.
AB  - BACKGROUND: In performing Vecchietti's operation laparoscopically, it is
      important to ensure bladder and rectum integrity. We report new techniques of
      ultrasonography and suture retrieval that simplify and improve the ease and speed
      of this operation. TECHNIQUE: The pneumoperitoneum is emptied and the bladder
      filled with 200 mL of sterile water. The ultrasound probe is placed on the
      suprapubic wall for a sagittal image. The needle progresses medially through the
      vesicorectal space, with ultrasound guidance, and its emergence into the pelvis
      is controlled with laparoscopy. The nylon sutures carrying the dilation ball are
      threaded through the needle and brought back through the abdominal wall.
      EXPERIENCE: Seven patients with vaginal aplasia had this procedure. There were no
      complications, and the mean operative time was 43 minutes (range 35-55). Mean
      vaginal length was 7 cm (range 6-10). Four women defined sexual intercourse as
      very satisfying and two as moderately satisfying. CONCLUSION: This original
      technique was used for easy, safe, and rapid creation of neovaginas.

PMID- 10074998
TI  - The risk-of-malignancy index to evaluate potential ovarian cancers in local
      hospitals.
AB  - OBJECTIVE: To assess the risk-of-malignancy index (a scoring system based on
      menopausal status, ultrasound features, and serum CA 125) at district hospitals
      for referral of women with suspected malignant pelvic masses for primary surgery
      at a central gynecologic oncology unit. METHODS: All seven hospitals in Health
      Region IV, Norway, agreed to refer women with pelvic masses and risk-of
      malignancy indices of 200 or more for centralized primary surgery. In total, 365
      women 30 years of age or older, admitted consecutively at the local hospitals,
      were enrolled in the study from February 1, 1995, to January 31, 1997. RESULTS:
      Compliance with the study was satisfactory; 84% (65 of 77) of women with risk-of
      malignancy indices of at least 200 were referred for centralized primary surgery.
      Sensitivity and specificity to malignancy were 71% and 92%, respectively, which
      is in agreement with previous validation of the risk-of-malignancy index in
      teaching hospital settings. False negatives were due mainly to stage Ia (18 of
      24) ovarian cancer, whereas 27 of 28 stage II-IV ovarian cancer cases were
      identified correctly. CONCLUSION: The risk-of-malignancy index identified women
      with malignant pelvic masses efficiently. Our study showed the risk-of-malignancy
      index strategy in a practical setting to be able to centralize primary surgery
      for advanced ovarian cancer from local hospitals to a subspecialty unit. We
      recommend the risk-of-malignancy index for detection of patients with advanced
      ovarian cancer for centralized primary surgery.

PMID- 10074999
TI  - The pill and the press: reporting risk.
AB  - Between 1986 and 1997, nine studies on health effects of oral contraceptives were
      published by the New England Journal of Medicine or JAMA. All of those studies
      showed no increased risk of breast cancer or protective effects against ovarian
      and endometrial cancer. Except for one study published in 1986, the major
      newspapers in the United States essentially ignored these findings, and The New
      York Times reported on other inconclusive studies that emphasized an oral
      contraceptive-breast cancer link.

PMID- 10075000
TI  - Screening for cystic fibrosis carrier state.
AB  - Carrier screening for cystic fibrosis as part of reproductive health care,
      including prenatal care, is not the standard of practice at this time. However, a
      recent National Institutes of Health Consensus Development Conference recommended
      that cystic fibrosis carrier screening should be offered to adults with a family
      history of cystic fibrosis, partners of individuals with cystic fibrosis, couples
      planning a pregnancy, and couples seeking prenatal testing. A workshop convened
      to discuss the implementation of these recommendations concluded that several
      issues must be resolved before these recommendations can be implemented. This
      commentary reviews the discussions that occurred and the conclusions that were
      reached at this workshop. Some of the subjects considered by the workshop
      participants were: the goals and outcomes of carrier screening; the continuum
      from making a test available to offering that test; to whom, when, and how cystic
      fibrosis testing should be offered; laboratory practice and quality assurance;
      provider and patient education; and insurance issues. The workshop participants
      concluded that those populations to whom carrier screening should be offered
      might include individuals and couples in high-risk groups who seek preconception
      counseling, infertility care, or prenatal care. High-risk groups include
      individuals of white northern European or of Ashkenazi-Jewish descent, those
      whose partners have cystic fibrosis, and those with a family history of cystic
      fibrosis. Before screening can be offered systematically to these individuals or
      couples, practice guidelines, educational materials for providers and patients,
      informed-consent protocols, and laboratory standards for testing must be
      developed.

PMID- 10075001
TI  - Fluorescence spectroscopy for diagnosis of squamous intraepithelial lesions of
      the cervix.
AB  - OBJECTIVE: To calculate receiver operating characteristic (ROC) curves for
      fluorescence spectroscopy in order to measure its performance in the diagnosis of
      squamous intraepithelial lesions (SILs) and to compare these curves with those
      for other diagnostic methods: colposcopy, cervicography, speculoscopy,
      Papanicolaou smear screening, and human papillomavirus (HPV) testing. DATA
      SOURCES: Data from our previous clinical study were used to calculate ROC curves
      for fluorescence spectroscopy. Curves for other techniques were calculated from
      other investigators' reports. To identify these, a MEDLINE search for articles
      published from 1966 to 1996 was carried out, using the search terms "colposcopy,"
      "cervicoscopy," "cervicography," "speculoscopy," "Papanicolaou smear," "HPV
      testing," "fluorescence spectroscopy," and "polar probe" in conjunction with the
      terms "diagnosis," "positive predictive value," "negative predictive value," and
      "receiver operating characteristic curve." METHODS OF STUDY SELECTION: We found
      270 articles, from which articles were selected if they reported results of
      studies involving high-disease-prevalence populations, reported findings of
      studies in which colposcopically directed biopsy was the criterion standard, and
      included sufficient data for recalculation of the reported sensitivities and
      specificities. TABULATION, INTEGRATION, AND RESULTS: We calculated ROC curves for
      fluorescence spectroscopy using Bayesian and neural net algorithms. A meta
      analytic approach was used to calculate ROC curves for the other techniques.
      Areas under the curves were calculated. Fluorescence spectroscopy using the
      neural net algorithm had the highest area under the ROC curve, followed by
      fluorescence spectroscopy using the Bayesian algorithm, followed by colposcopy,
      the standard diagnostic technique. Cervicography, Papanicolaou smear screening,
      and HPV testing performed comparably with each other but not as well as
      fluorescence spectroscopy and colposcopy. CONCLUSION: Fluorescence spectroscopy
      performs better than colposcopy and other techniques in the diagnosis of SILs.
      Because it also permits real-time diagnosis and has the potential of being used
      by inexperienced health care personnel, this technology holds bright promise.

PMID- 10075003
TI  - Criteria that indicate endometriosis is the cause of chronic pelvic pain.

PMID- 10075004
TI  - Fertility options for patients with stages IA2 and IB cervical cancer:
      presentation of two cases and discussion of technical and ethical issues.

PMID- 10075005
TI  - Localization of protein gene product 9.5 immunoreactivity in derivatives of the
      human Wolffian duct and in prostate cancer.
AB  - BACKGROUND: Protein gene product 9.5 (PGP 9.5) has been considered to be a
      neuronal marker, but it is also present in extraneuronal tissues, e.g., the human
      mammary gland and rat epididymis. Its presence and distribution in the developing
      and adult male human genital tract have been unknown. METHODS:
      Immunohistochemical reactions were performed on human embryonic and postnatal
      specimens of the male genital tract, using commercial monoclonal and polyclonal
      antibodies. RESULTS: PGP 9.5 immunoreactivity was found in the Wolffian duct of
      human embryos (55-85 mm crown-rump length). Strong reactivity was observed in
      mesonephric tubular cells and at the apical rim of Wolffian duct cells. Owing to
      their PGP 9.5 immunoreactivity, these cells could also be identified on the
      surface of the embryonic verumontanum, extending from the orifices of the
      Wolffian duct to a small stretch of the urogenital sinus. There they contrasted
      sharply against non-Wolffian cells. In the adult human genital tract, PGP 9.5
      immunoreactive material was present in the supranuclear portion of some
      epithelial cells of the epididymal efferent ductules, in isolated cells of the
      ejaculatory ducts, and in prostate cancer specimens. In the ejaculatory ducts,
      the PGP 9.5-immunoreactive cells were free of immunoreactivity for semenogelin,
      the major secretory product of the ejaculatory-vesicular-ampullary complex, and
      they also lacked chromogranin A-immunoreactivity. In prostate cancer specimens,
      PGP 9.5 immunoreactivity was never observed in secretory cells (immunoreactive
      for prostate-specific antigen), but was restricted to neuroendocrine cells, where
      it occurred either alone or coexpressed with chromogranin A-immunoreactivity.
      CONCLUSIONS: PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian
      duct and its derivations; postnatally, it is restricted to a few cells derived
      from the initial and terminal segment of the Wolffian duct, and to neuroendocrine
      cells in prostate cancer specimens.

PMID- 10075006
TI  - Early castration-induced upregulation of transforming growth factor beta1 and its
      receptors is associated with tumor cell apoptosis and a major decline in serum
      prostate-specific antigen in prostate cancer patients.
AB  - BACKGROUND: The mechanism behind castration-induced apoptosis in prostate cells
      is unknown, but data from other species suggest that transforming growth factor
      beta1 (TGF-beta1) may be involved. METHODS: By using quantitative RT-PCR and
      immunohistochemistry, expression of TGF-beta1 and its receptors type I and II (RI
      and RII) was studied in normal and tumor areas of core biopsies taken before and
      2-11 days after castration therapy. The TGF-beta responses were related to
      changes in apoptotic index and to changes in serum prostate-specific antigen
      (PSA). RESULTS: In normal prostate tissue, apoptosis was generally increased by
      castration, and apoptosis was accompanied by an increase in TGF-beta1 and RII
      mRNA levels (P < 0.05). In tumors, apoptosis was seen only in 44% of the cases
      and in these, but not in the others, TGF-beta1, RI, and RII mRNA levels were
      increased (P < 0.05). In the patients showing a prognostically favorable PSA
      response (nadir PSA <5 ng/ml), but not in the others, RI and RII mRNA levels were
      significantly upregulated (P < 0.05). CONCLUSIONS: Short-term upregulation of TGF
      beta1 and its receptors is associated with apoptosis in human prostate and
      prostate cancer, and possibly with a favorable clinical outcome after castration
      therapy.

PMID- 10075007
TI  - Prognostic significance of beta-microseminoprotein mRNA expression in prostate
      cancer.
AB  - BACKGROUND: Human beta-microseminoprotein (beta-MSP or PSP94) is a small protein
      secreted by prostatic epithelial cells. We recently reported the presence of low
      levels of beta-MSP mRNA expression and protein in most prostate cancer tissues.
      METHODS: Beta-MSP and mRNA expression was examined by in situ hybridization in
      biopsy specimens obtained from 92 patients with prostate cancer. All tissue
      specimens were obtained by needle biopsies prior to treatment. All patients
      subsequently received endocrine therapy. To estimate the influence of beta-MSP
      mRNA expression and three possible prognostic factors, i.e., patient age,
      clinical stage, and Gleason score, on time to progression under endocrine
      therapy, univariate and multivariate analyses were performed using Cox's
      proportional hazards regression model. RESULTS: Multivariate survival analysis
      showed that clinical stage was the strongest prognostic factor (P = 0.006) and
      that beta-MSP mRNA expression was the second strongest factor (P = 0.038) in 92
      patients with stage B-D disease. Analysis of only 51 patients with stage D
      disease showed that beta-MSP mRNA expression was the only significant prognostic
      indicator for progression under endocrine therapy (P = 0.003). CONCLUSIONS: The
      presence of cells that express the beta-MSP transcript may be a novel indicator
      of potentially aggressive prostate cancer.

PMID- 10075008
TI  - CeReS-18 inhibits growth and induces apoptosis in human prostatic cancer cells.
AB  - BACKGROUND: Polypeptide growth factors are positive and negative regulators of
      prostatic growth and function, and many positive regulators of growth in the
      prostate have been extensively studied. However, very few inhibitors of prostate
      cell proliferation have been identified. We have isolated a unique 18-kDa
      sialoglycopeptide (CeReS-18) which inhibits cell proliferation of three separate
      lines of human prostate cancer cells, as well as inducing cellular cytotoxicity
      via an apoptotic pathway unrelated to the Bcl-2 family of proteins. METHODS: Cell
      cycle inhibition was analyzed by direct cell counts with a Coulter (Miami, FL)
      cell counter. Apoptotic cells were analyzed by electron microscopy, annexin V
      fluorescein isothiocyanate (FITC) staining, fluorescence microscopy, and
      propidium iodide uptake measured with a fluorescence-activated cell sorter.
      Expression of the proteins of the Bcl-2 family was detected by Western blot
      analysis. RESULTS: We found that CeReS-18 inhibits cell proliferation of androgen
      responsive, LNCaP.FGC human prostate cancer cells, as well as of androgen
      nonresponsive DU-145 and PC3 human prostate cancer cells. Furthermore a, fivefold
      increase over the inhibitory concentration of CeReS-18 elicited a cytotoxic
      response by all three cell lines. We thus characterized the cytotoxic mechanism
      as apoptotic in nature, and we measured the expression of several members of the
      Bcl-2 family in PC3 cells upon treatment with CeReS-18. CONCLUSIONS: The data
      indicate that CeReS-18 is a potent inhibitor of cellular progression through the
      cell cycle by both androgen-responsive and androgen-nonresponsive human prostate
      cancer cells. In addition, treatment of both types of cells with increased
      concentrations of CeReS-18 induces cellular cytotoxicity, characterized as
      apoptosis.

PMID- 10075009
TI  - Efficiency of prostate-specific antigen and digital rectal examination in
      screening, using 4.0 ng/ml and age-specific reference range as a cutoff for
      abnormal values.
AB  - BACKGROUND: The purpose of this study was to examine the diagnostic efficiency of
      prostate-specific antigen (PSA) and digital rectal examination (DRE) testing when
      using either 4.0 ng/ml or an age-specific reference range (ASRR) as an abnormal
      cutoff PSA value. METHODS: Between 1992-1995, 116,073 men, aged 40-79 years, were
      screened during Prostate Cancer Awareness Week. When using a 4.0-ng/ml cutoff PSA
      value, 22,014 had either an abnormal PSA, an abnormal DRE, or both. When using an
      ASRR cutoff PSA value, 17,561 had either an abnormal PSA, an abnormal DRE, or
      both. The positive predictive value (PPV), sensitivity, and specificity of PSA,
      DRE, and combined PSA and DRE tests were evaluated. RESULTS: When using a 4.0
      ng/ml cutoff PSA value, the PPVs of abnormal PSA alone, abnormal DRE alone, and
      combined abnormal PSA and DRE tests were 27.7%, 17.7%, and 56.0%, respectively.
      Sensitivities were 34.9%, 27.1%, and 38.0%, respectively. Specificities were
      63.1%, 49.0%, and 87.9%, respectively. When using an ASRR cutoff PSA value, the
      PPVs of each category were 31.8%, 20.8%, and 63.7%, respectively. Sensitivities
      were 27.1%, 41.0%, and 31.8%, respectively. Specificities were 75.0%, 32.8%, and
      92.2%, respectively. The PPVs of the PSA test were higher than those of the DRE.
      The PPVs of combined tests were highest when using either a 4.0-ng/ml cutoff PSA
      value or an ASRR cutoff PSA value (all P < 0.001). When using an ASRR, the PPVs
      of PSA, DRE, and combined tests were higher than those when using a 4.0-ng/ml
      without statistical significance (all P > 0.05). Sensitivity of PSA when using an
      ASRR was lower than when using 4.0 ng/ml. CONCLUSIONS: Significantly higher PPVs
      indicated that utilizing both a PSA test and a DRE is most effective in screening
      for the early detection of prostate cancer. Although higher PPVs when using an
      ASRR cutoff PSA value suggested fewer unnecessary biopsies, lower sensitivities
      resulted in fewer cancers detected. Thus, we recommend that the combination of a
      PSA test with a cutoff value of 4.0 ng/ml and a DRE should continue to be
      utilized in the screening programs.

PMID- 10075010
TI  - Chromosomal clues to the development of prostate tumors.
AB  - BACKGROUND: Cytogenetic, molecular cytogenetic, and molecular studies of prostate
      cancer have revealed an enormous amount of data regarding chromosomal loci that
      are aberrant in prostate tumors. METHODS: These data have been compared and
      condensed in this review to determine which chromosomes and chromosome sites have
      been most frequently reported. RESULTS: Loss of the Y chromosome, gain of 7, 8,
      and X, and interstitial deletions on 6q, 7q, 8p, 10q, 13q, 16q, 17q, and 18q are
      the most prevalent. CONCLUSIONS: A potential model for genetic control of tumor
      progression is presented, as are data regarding the evaluation of a new series of
      tumors.

PMID- 10075011
TI  - Novel concept of antisurvival factor (ASF) therapy produces an objective clinical
      response in four patients with hormone-refractory prostate cancer: case report.
AB  - BACKGROUND: Osteoblasts and osteoblast-derived survival growth factors, such as
      insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate
      cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro.
      METHODS: We tested a novel therapeutic approach, referred to as antisurvival
      factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using
      dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived
      IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (i.m.),
      q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce
      a clinical response in 4 patients with progressing hormone-refractory prostate
      cancer. RESULTS: The patients given ASF therapy exhibited an excellent
      improvement of clinical performance and a decline of prostate-specific antigen
      (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical
      response (normalization of PSA), two experienced good clinical response (decline
      of PSA of more than 50%), and one experienced stabilization (decline of PSA of
      less than 50%). CONCLUSIONS: We conclude that this novel concept of combination
      therapy, using ASF with hormone ablation, is a promising salvage therapy that
      should be further assessed with a randomized clinical trial.

PMID- 10075012
TI  - 1998 International Symposium on Biology of Prostate Growth. Bethesda, Maryland,
      USA. March 15-18, 1998. Abstracts.

PMID- 10075013
TI  - Signalling of Bruton's tyrosine kinase, Btk.
AB  - Bruton's tyrosine kinase, which is encoded by the BTK gene, is a cytoplasmic
      protein tyrosine kinase (PTK) crucial for B-cell development and differentiation.
      It belongs to the Tec family of PTKs containing several domains that are
      characteristic of signalling molecules. In humans, mutations that disrupt the
      function of this gene lead to the classical XLA syndrome (X-linked
      agammaglobulinaemia), a primary immunodeficiency mainly characterized by lack of
      mature B cells as well as low levels of immunoglobulins. In contrast, animal
      models of this disease such as the xid mice display profoundly milder XLA
      phenotype. BTK phosphorylation and activation in response to engagement of the B
      cell receptor (BCR) by antigen is a dynamic process whereby a variety of proteins
      interact with each other and recruit signalling molecules resulting in a
      physiological response such as B-cell proliferation and antibody production. The
      main players, however, that participate in the intracellular downstream cascade
      have not yet been identified and are therefore under intense scrutiny in several
      laboratories. This review discusses certain aspects of BTK activation following
      receptor stimulation by agonists and how this event is translated into the
      biochemical signals within the cell that eventually lead to nuclear responses.

PMID- 10075014
TI  - Paroxysmal nocturnal haemoglobinuria: the disease and a hypothesis for a new
      treatment.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is a disease entity that presents with
      intravascular haemolysis and an increased tendency for venous thrombosis. In
      recent years there has been a major breakthrough in our understanding of the
      pathogenesis of PNH. Most of the different symptoms can be tracked down to the
      deficiency of glycophosphoinositol (GPI)-anchored proteins in cell lines deriving
      from a single haematopoietic stem cell. This deficiency is caused by a mutation
      in the X-chromosomal PIG-A gene whose product, a glycosyltransferase,
      participates in the first step of the GPI-anchor biosynthesis. Lack of GPI-linked
      complement inhibitors CD55 and CD59 predisposes red blood cells to lysis. The
      main unresolved question is why the stem cells lacking GPI-anchored surface
      proteins gain a growth advantage over their normal counterparts. So far, our
      progress in understanding the pathogenesis has not resulted in better treatment
      of PNH and new ideas are warranted. In this regard, we propose a new mode of
      treatment for PNH by exploiting the increased susceptibility of affected bone
      marrow precursor cells to complement and targeting complement attack against them
      by a specific complement-activating monoclonal antibody.

PMID- 10075015
TI  - Cyclosporin A suppresses the induction of nitric oxide synthesis in interferon
      gamma-treated L929 fibroblasts.
AB  - The effects of immunosuppressant cyclosporin A (CsA) on nitric oxide (NO)
      production and inducible NO synthase (iNOS) activity in murine L929 fibroblasts
      were investigated. IFN-gamma-induced NO production in L929 cells was mediated
      through an iNOS-dependent L-arginine-NO pathway, since it was abrogated by a
      selective inhibitor of iNOS, aminoguanidine. CsA applied simultaneously with IFN
      gamma caused a dose-dependent reduction of NO synthesis in L929 cells. However,
      CsA did not influence the enzymatic activity of iNOS, since it failed to affect
      NO production in cells in which iNOS had already been induced with IFN-gamma and
      any further induction was blocked by the protein-synthesis inhibitor
      cycloheximide. IFN-gamma-triggered expression of mRNA for interferon regulatory
      factor-1 was not reduced by CsA-treatment, suggesting that this iNOS
      transcription factor is not a target in CsA-mediated inhibition of NO synthesis.
      Finally, FK506 was not able to mimic the inhibitory effect of CsA on NO
      production in L929 cells, indicating the calcineurin-independent mechanism of CsA
      action. These results indicate that CsA suppresses NO synthesis in L929 cells
      independent of calcineurin inhibition, and interfering with intracellular
      pathways involved in the iNOS induction, rather than inhibiting its enzymatic
      activity.

PMID- 10075016
TI  - The role of amoebocytes in endotoxin-mediated coagulation in the innate immunity
      of Achatina fulica snails.
AB  - Achatina amoebocyte lysate (AAL) derived from amoebocytes of Achatina fulica was
      activated by Gram-negative bacterial endotoxins in a time-dependent manner
      resulting in gel formation/coagulation. The activation and maximum proliferation
      of amoebocytes was observed 40 min after intramuscular injection (20
      microg/snail) of endotoxin. Endotoxin-mediated proteolytic activity of AAL
      towards a serine-protease-specific chromogenic substrate was maximum at pH 8.0,
      37 degrees C and within 15 min in a divalent-cation-dependent manner. The AAL
      activity induced by the endotoxin was directly dependent on the endotoxin
      concentration, showed a high specificity and saturated at higher endotoxin
      concentrations. An endotoxin-sensitive factor (ESF) was purified from AAL to
      apparent homogeneity by single-step affinity chromatography on a heparin
      Sepharose 4B column. Native ESF of molecular weight 140 000 was composed of two
      identical subunits of molecular weight 70 000 attached through non-covalent
      association. A strong binding to endotoxin (Escherichia coli 055:B5) was
      exhibited by ESF with a 40-fold higher biological activity than AAL. The ESF was
      shown to have a unique Phe-Ile active site with regard to its alternate
      activation by alpha-chymotrypsin instead of endotoxin. The ESF was characterized
      as a serine protease type as evidenced by potent inhibition with specific
      inhibitors.

PMID- 10075017
TI  - Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta
      induced signal transduction pathways in IL-2 and TGF-beta secretion and
      proliferation in the thymoma cell line EL4.NOB-1.
AB  - In the present study we investigated the interleukin (IL)-1beta and transforming
      growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2
      and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant
      to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1
      induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth
      promoting activity that could be antagonized by adding the phosphatidyl choline
      dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme
      inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase
      (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC
      PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all
      investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to
      inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are
      involved in TGF-beta autoinduction that is accompanied by a secretion of the
      active but not the latent growth factor and is antagonized by IL-1beta. Addition
      of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone,
      resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active
      TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of
      latency and secretion. Analysis of specific tyrosine activity and c-Fos
      expression showed synergistic but no antagonistic effects. These events are
      therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta
      production, but might participate in IL-1/TGF-beta-induced growth promotion.

PMID- 10075018
TI  - Diverse T-cell receptor CDR3 length patterns in human CD4+ and CD8+ T lymphocytes
      from newborns and adults.
AB  - T cells are essential in the initiation and maintenance of immune responses.
      Specific interaction between T cells and a presumptive antigen occurs through
      recognition of an MHC-peptide complex by the T-cell receptor (TCR). The
      complementarity-determining region (CDR) 3 of the TCR has direct contact with the
      peptide. Here we describe CDR3 length variability of six different TCRBV gene
      families of CD4+ and CD8+ umbilical cord (UC) and peripheral blood (PB) T cells.
      Amplified products spanning the TCR CDR3 regions from CD4+ PB, CD4+ UC and CD8+
      UC blood T cells typically displayed Gaussian-like distributions. In contrast,
      profound and frequent perturbations were recorded in CD8+ PB lymphocytes, with a
      non-Gaussian pattern in more than half of the samples studied. A substantial
      portion of the perturbed CD8+ subsets were clonal or oligoclonal, as determined
      by CDR3-length restriction, TCRBJ gene usage and nucleotide sequencing. This
      implies that the conditions for shaping and maintenance of the peripheral TCR
      repertoire are profoundly different for CD8+ and CD4+ T cells.

PMID- 10075019
TI  - Bruton's tyrosine-kinase-deficient murine B lymphocytes fail to enter S phase
      when stimulated with anti-immunoglobulin plus interleukin-4.
AB  - One of the earliest recognized defects of B cells carrying the xid mutation in
      the gene encoding for Bruton's tyrosine kinase (Btk) was their inability to
      proliferate in response to anti-immunoglobulin plus interleukin (IL)-4
      stimulation. Previous attempts to define the stage at which this proliferative
      block occurred using xid B cells provided dissimilar results. We decided to
      reinvestigate this question using B cells from C57BL/6-Btk-protein-deficient
      (BtkM) mice. Upon stimulation with anti-IgM and IL-4, BtkM cells increase in size
      and up-regulate early activation markers such as CD69 and B7-2, however, they do
      not progress into the cell cycle further than a very early G1 stage. They down
      regulate the cyclin-dependent kinase (cdk) inhibitor p27 to some extent but fail
      to up-regulate the G1-phase cyclins D2 and E and the retinoblastoma protein (pRb)
      remains hypo-phosphorylated. While approximately 25% of the wild-type cells enter
      S phase after 36 h stimulation, only 1% of the BtkM cells do so. The
      proliferative responsiveness of the BtkM cells is restored when the phorbol ester
      phorbol 12,13-di-butyrate (PDBu) is added to the anti-IgM plus IL-4 cultures.
      Collectively, our data demonstrate that a dramatically reduced frequency of
      responsive cells underlies the low proliferation of anti-IgM plus IL-4-stimulated
      Btk-deficient B cells and point towards an early block in the G1 phase due to
      inadequate activation of a pathway that regulates PKC activation.

PMID- 10075020
TI  - Immunization with a synthetic peptide conjugate derived from the N-terminal
      sequence of either the beta-chain of haemoglobin or the immunosuppressive protein
      (reOLT 4) reduces the litter size of pregnant rats.
AB  - A synthetic peptide conjugate based on the N-terminal sequence of a 10 000 MW
      immunosuppressive serum protein (reOLT 4) was used to immunize female Lewis rats
      prior to mating, in order to determine whether blocking this protein had an
      effect on pregnancy. The N-terminal sequence of (reOLT 4) has close sequence
      homology to the beta-chain of rat haemoglobin so a peptide conjugate based on the
      N-terminal sequence of this protein was also used to immunize female Lewis rats.
      Controls included animals that were not immunized and animals that received the
      peptide carrier, diphtheria toxoid (DT). No statistical differences were found in
      gestation time or litter sizes in these groups. Differences were, however,
      evident between these groups and animals that received DT-(reOLT 4) (group 4) or
      the DT-beta-chain haemoglobin (group 5). There were no statistical differences in
      litter size or gestation time for group 4 when compared with group 5. Enzyme
      linked immunosorbent assay and dot-blot analysis revealed that rats from both
      groups also had strong responses against DT, the peptide conjugate they were
      immunized with and the corresponding full-length protein. In both cases, animals
      from group 4 and group 5 had weak responses to the peptide that they did not
      receive, together with lower erythrocyte counts and haematocrits, and elevated
      heart to body weight ratios. Additionally, antibody purified on a (reOLT 4)
      immunoaffinity column was capable of binding to rat erythrocytes. A second
      investigation comparing anaemia prior to fertilization and maintained anaemia
      over the gestation period revealed that only the latter was capable of decreasing
      litter size to the same degree as obtained for groups 4 and 5. We conclude that
      for groups 4 and 5 it is the autoimmune effect of continual anaemia over the
      gestation period, mediated by autoantibodies, which results in the observed lower
      litter size.

PMID- 10075021
TI  - Interleukin-4-mediated inhibition of nitric oxide production in interferon-gamma
      treated and virus-infected macrophages.
AB  - Upon interferon-gamma (IFN-gamma) stimulation, murine macrophages (Mphi) produce
      nitric oxide (NO) through expression of inducible nitric oxide synthase (iNOS).
      Interleukin (IL)-4 treatment, even delayed 12 h relative to IFN-gamma,
      antagonized this induction, whereas infection with herpes simplex virus type 2
      (HSV-2) or treatment with tumour necrosis factor-alpha exerted a synergistic
      effect, which partly compensated for the antagonistic effect of IL-4. Neither IL
      4 nor HSV-2 affected the IFN-gamma-activated Jak-STAT (Janus kinase-signal
      transducer and activator of transcription) pathway or altered the levels of IFN
      gamma-induced interferon regulatory factor (IRF)-1 expression, which is STAT1
      dependent and known to play a central role in IFN-gamma-mediated gene induction.
      The effect of IL-4 was completely dependent on de novo protein synthesis,
      indicating that a direct activation of latent inhibitors is not sufficient to
      explain the inhibitory effect of IL-4. Furthermore, IL-4 substantially augmented
      the IFN-gamma-induced expression of IRF-2, which is known to compete with IRF-1
      for the DNA recognition site, ISRE (interferon-stimulated response element). Our
      findings could indicate that IL-4 suppresses IFN-gamma-stimulated iNOS
      transcription by elevating the level of IRF-2 which, through competition,
      prevents IRF-1 from binding to ISRE in the iNOS promoter. The virus-induced
      effects on iNOS and NO levels in IFN-gamma-stimulated Mphi do not seem to involve
      the Jak/STAT pathway or a differential expression of IRF-1 and IRF-2.

PMID- 10075022
TI  - Phenotypic and functional properties of dendritic cells isolated from human
      peripheral blood in comparison with mononuclear cells and T cells.
AB  - Dendritic cells (DCs) are pivotal for antigen presentation, T-cell priming and B
      cell functions. Few studies have been carried out on DCs in human diseases,
      partly because the current procedures used for DC preparation include elaborate
      negative selection with monoclonal antibodies (MoAb) and prolonged culture in
      cytokine-enriched milieu, which may influence DC functions. Using physical
      density and their adherent properties, DCs were prepared from the blood of
      healthy subjects. Approximately 2% of human blood mononuclear cells (MNC) were
      shown to consist of DCs, yielding DCs of 80-90% purity. They expressed markers
      related to DCs (CD1a, CD11c, CD32 and CD83), costimulatory molecules (CD40, CD80,
      CD86), human leucocyte antigen (HLA) class I and II molecules and inducible
      nitric oxide (NO) synthase (NOS2), and lacked lymphocyte and monocyte markers
      (CD3, CD19, CD20, CD56 and CD14). Compared with blood MNC and T cells, DCs showed
      a high level of spontaneous proliferation and nitric oxide production, as well as
      strong proliferative responses in mixed leucocyte reactions. Enzyme-linked
      immunospot (ELISPOT) assays revealed higher levels of interleukin (IL)-4-, IL-10-
      and interferon-gamma (IFN-gamma)-secreting cells among DCs than among MNC or T
      cells obtained from the same blood specimens, while levels of tumour necrosis
      factor-alpha (TNF-alpha)- and IL-6-secreting cells did not differ. The results
      demonstrate that the method used is fast, effective and competitively priced, and
      should be useful for studies of DCs in disease states.

PMID- 10075023
TI  - Photodynamic alteration of the surface receptor expression pattern of murine
      splenic dendritic cells.
AB  - The photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA,
      verteporfin), in combination with visible light irradiation, a clinical procedure
      termed photodynamic therapy (PDT), has immunomodulatory activity in various mouse
      models. We studied the impact of BPD-MA and light upon DBA/2 mouse splenic
      dendritic cells (DC), a potent antigen-presenting cell (APC) type. DC treated
      with nanomolar amounts of BPD-MA and 690 nm wavelength light had a reduced
      capacity to stimulate the proliferation of alloreactive T cells. Treatment with
      BPD-MA and light reduced DC levels of major histocompatibility (MHC) Class I and
      II antigens, intercellular adhesion molecule-1 (ICAM-1, CD54), the costimulatory
      B7-1 (CD80) and B7-2 (CD86) molecules, leucocyte common antigen CD45, the
      apoptosis-regulating Fas (CD95) receptor and the integrin CD11c. In contrast, DC
      expression of leucocyte function-associated-1 (LFA-1, CD11a), Mac-1 (CD11b),
      integrin beta2 chain (CD18) and the DEC-205 receptor increased, while CD40 levels
      were relatively unchanged 24 h after the treatment. MHC Class I and ICAM-1 levels
      decreased to 40% of control levels within 2 h following the photodynamic
      treatment. In the absence of light, BPD-MA did not affect DC receptor levels.
      Changes in DC receptor levels produced by BPD-MA and red light were similar to
      those produced by ultraviolet B light irradiation. The photodynamic treatment of
      activated splenic B cells, a separate APC class, had little effect upon receptor
      expression, except that MHC Class II levels were moderately decreased 24 h later.
      Changes in DC receptor expression may contribute to the immunomodulatory action
      of PDT.

PMID- 10075024
TI  - Mannan-binding lectin deficiency is associated with unexplained recurrent
      miscarriage.
AB  - Mannan-binding lectin (MBL) is a plasma protein which, upon binding to microbial
      carbohydrate structures, elicits activation of the complement system. The level
      of MBL is genetically determined. It has been reported that the frequency of low
      plasma levels of MBL is increased in patients with unexplained recurrent
      miscarriages (RM). In the present study plasma MBL levels were determined in 146
      Danish women with RM and 41 of their husbands together with 49 Scottish RM women
      and 41 of their husbands. In both countries MBL levels were also investigated in
      a total of 444 controls. Based on the control data, a cut-off MBL level < 50
      ng/ml was selected to define MBL deficiency. The typical odds ratio for MBL
      deficiency among female patients in the two populations was 1.68 (95% confidence
      limits 1.01-2.80, P<0.05) whereas it was 1.57 (95% confidence limits 0.72-3.42,
      not significant) for the male partners of the patients. There was a significant
      correlation between the frequency of MBL deficiency in RM women and the number of
      previous miscarriages (P < 0.01), whereas no such correlation was found in the
      husbands. The results indicate that maternal MBL deficiency is associated with
      RM. Maternal MBL deficiency might impair the immune defence against
      microorganisms at the feto-maternal interface.

PMID- 10075025
TI  - Normal T-helper 1/T-helper 2 balance in peripheral blood of coeliac disease
      patients.
AB  - Activated T cells, with their secretion of cytokines, probably play an important
      role in the pathogenesis of mucosal lesions in coeliac disease (COD) and the
      prominence of a T-helper (Th)1-type cytokine pattern has been reported. As the
      process of immunological activation in the jejunal mucosa in active CoD has been
      shown to also cause some differences in peripheral blood lymphocyte populations,
      we sought to establish any changes in the Th 1/Th2 balance in peripheral blood of
      patients, at different stages of CoD, relative to healthy individuals. Twenty-two
      CoD patients and 10 healthy controls were included in the study. The Th1/Th2
      balance was examined both in resting cells and after polyclonal stimulation using
      two different methods: intracytoplasmic cytokine contents were measured using an
      intracellular staining method and three-colour flow cytometry and cytokine
      contents of cell culture supernatants were measured using traditional enzyme
      linked immunosorbent assays (ELISAs). Interferon-gamma (IFN-gamma)-producing
      cells (Thl) were as prominent in untreated CoD patients and treated CoD patients
      as in healthy controls, while cells fitting a Th2 or ThO-type cytokine pattern
      were few in all groups. In ELISA assays, Th1 type (IFN-gamma or interleukin (IL)
      2) cytokines were again prominent in all study groups but no statistically
      significant differences were found in IFN-gamma, IL-4 or IL-2 levels among the
      three groups. These results suggest that the increased shift towards a Th1
      response is mainly restricted to the actual site of inflammation and that
      circulating T cells do not show a similar response, presumably because activated
      cells in peripheral blood are too few. Further research on cytokine profiles
      measuring T-cell activation in CoD should be focused on the actual tissue of
      inflammation.

PMID- 10075026
TI  - Relationship between interleukin-5 production and variations in eosinophil counts
      during HIV infection in West Africa: influence of Mycobacterium tuberculosis
      infection.
AB  - Eosinophils are important effectors of the non-specific immune response and we
      studied whether perturbations in the production of the type 2 cytokine,
      interleukin-5 (IL-5), could account for the variations in eosinophil counts
      observed in human immunodeficiency virus (HIV) infection. HIV-infected patients
      without helminthiasis were investigated in a cross-sectional study in West
      Africa. Eosinophil counts were significantly higher in CDC-B patients than in
      controls, but were dramatically decreased at the CDC-C stage. Phorbol 12
      myristate 13-acetate (PMA)+ ionomycin-induced IL-5 production by peripheral blood
      mononuclear cells (PBMC) was decreased from the A stage of the disease, and
      significant correlations were observed between IL-5 production and eosinophil
      counts in tuberculosis (TB)-negative HIV-1-positive, TB-positive HIV-1-positive
      and TB-positive HIV-negative patient groups. Nevertheless, the production of IL-5
      was not decreased in HIV-positive patients with TB, in contrast to HIV-positive
      patients without TB presenting with the same ranges of CD4+ counts. Our data
      suggest that, during HIV infection, the impairment in IL-5 production is one of
      the factors associated with the 'paradoxal' eosinopenia observed in tropical
      areas, but that IL-5 production during active TB is compensated by cellular
      subsets, yet to be identified.

PMID- 10075027
TI  - In vitro synthesis of interferon-gamma, interleukin-4, transforming growth factor
      beta and interleukin-1 beta by peripheral blood mononuclear cells from
      tuberculosis patients: relationship with the severity of pulmonary involvement.
AB  - Given the role of cell-mediated immune responses in resistance to mycobacteria,
      we sought to analyse whether there was a relationship between the severity of
      pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro
      cytokine production. To achieve this, 25 untreated TB patients showing mild (n =
      5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12 age-matched
      healthy controls (mean+/-SD, 37+/-14.5 years) were studied. Peripheral blood
      mononuclear cells were cultured for 5 days with 10 microg/ml whole, sonicated
      Mycobacterium tuberculosis (WSA) or 2.5 microg/ml Concanavalin A (Con A).
      Supernatants were collected on day 4, from cultures grown with or without WSA,
      for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1beta and
      transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was
      found to be reduced among patients and more profound in those with advanced
      disease who also displayed a depressed response to Con A. Patients with mild TB
      showed a preferential production of IFN-gamma over IL-4, gave the highest level
      of IFN-gamma synthesis upon specific antigen stimulation and showed increased
      levels of IL-1beta production. Findings in patients with moderate TB appeared
      compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher
      synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease
      showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily
      noticeable, yet decreased in comparison with the other patient groups.
      Differences in cytokine response according to the amount of lung involvement
      suggest a role for such mediators in the immunopathogenesis underlying the
      distinct clinical forms of pulmonary TB, that is a predominant T helper Th)1-like
      or Th2-like activity in mild or in progressive TB, respectively.

PMID- 10075028
TI  - Advertisements for ourselves--let's be cautious about interpreting outcome
      studies of critical care services.

PMID- 10075029
TI  - Mechanisms and management of myocardial dysfunction in septic shock.

PMID- 10075030
TI  - Continuous monitoring of cardiac output--advanced technology for advanced patient
      care?

PMID- 10075031
TI  - Autopsies in the ICU: we still need them!

PMID- 10075032
TI  - Toward new definitions of acute respiratory distress syndrome.

PMID- 10075033
TI  - TNF in trauma--whither our focus?

PMID- 10075034
TI  - Tumor necrosis factor receptor expression on inflammatory cells in sepsis.

PMID- 10075035
TI  - Catecholamines and the splanchnic circulation.

PMID- 10075036
TI  - Cellular drug interaction in the fight against multidrug resistant cancer.

PMID- 10075037
TI  - Predicting extubation failure after open-heart surgery: can we harness the
      strength of large clinical databases?

PMID- 10075038
TI  - Nitric oxide and the gut: one more piece in the puzzle.

PMID- 10075039
TI  - Cardiovascular responses to scorpion venom.

PMID- 10075040
TI  - In search of the "magic nutraceutical".

PMID- 10075041
TI  - PEEP: blood gas cosmetics or a therapy for ARDS?

PMID- 10075042
TI  - Expired nitric oxide and shock in higher order species.

PMID- 10075043
TI  - Total splanchnic resuscitation, SIRS, and MODS.

PMID- 10075044
TI  - Early enteral nutritional support improves outcome: hypothesis or fact?

PMID- 10075045
TI  - Narcotics for brain-injured patients? At what cost?

PMID- 10075046
TI  - Brain death and evoked potentials in pediatric patients.

PMID- 10075047
TI  - A cost analysis of enterally administered lorazepam in the pediatric intensive
      care unit "out of the orphanage".

PMID- 10075048
TI  - Possible allegations of sexual abuse in an intensive care unit: an editorial.

PMID- 10075049
TI  - Effects of an organized critical care service on outcomes and resource
      utilization: a cohort study.
AB  - OBJECTIVE: To determine whether the presence of an on-site, organized, supervised
      critical service improves care and decreases resource utilization. DESIGN: The
      study compared two patient cohorts admitted to a surgical intensive care unit
      during the same period of time. The study cohort was cared for by an on-site
      critical care team supervised by an intensivist. The control cohort was cared for
      by a team with patient care responsibilities in multiple sites supervised by a
      general surgeon. The main outcome measures were duration of stay, resource
      utilization, and complication rate. SETTING: Study patients were general surgical
      patients in an academic medical center. RESULTS: Despite having higher Acute
      Physiology and Chronic Health Evaluation II scores, patients cared for by the
      critical care service spent less time in the surgical intensive care unit, used
      fewer resources, had fewer complications and had lower total hospital charges.
      The difference between the two cohorts was most evident in patients with the
      worst APACHE II score. CONCLUSIONS: Critical care interventions are expensive and
      have a narrow safety margin. It is essential to develop structured and validated
      approaches to study the delivery of this resource. In this study, the critical
      care service model performed favorably both in terms of quality and cost.

PMID- 10075050
TI  - Fiber atrophy, but not changes in acetylcholine receptor expression, contributes
      to the muscle dysfunction after immobilization.
AB  - OBJECTIVES: Muscle weakness associated with critical illness can be due to the
      illness itself, immobilization associated with it, and/or to concomitant use of
      drugs that affect neuromuscular transmission. This study investigated the
      contribution of immobilization per se to the muscle dysfunction, as well as the
      associated morphologic and biochemical changes. DESIGN: Prospective, laboratory
      study. SETTING: Hospital research laboratory. SUBJECTS: Adult, male, Sprague
      Dawley rats, weighing 200 to 250 g, were randomly allocated to three experimental
      groups, depending on the duration (7, 14, or 28 days) of limb immobilization (n =
      9 to 11 per group) or sham immobilization (n = 5 to 6 per group). INTERVENTIONS:
      Chronic, unilateral immobilization (disuse) of the tibialis cranialis muscle was
      produced by fixing the knee and ankle joints at 90 degrees flexion. The
      contralateral unimmobilized leg and a separate group of sham-immobilized legs
      served as controls. MEASUREMENTS AND MAIN RESULTS: After 7, 14, or 28 days of
      disuse of the tibialis muscles, the peak isometric twitch (Pt) and tetanic (Po)
      tensions, as well as fatigability during 5 secs of nerve stimulation at 50, 100,
      and 150 Hz, were measured simultaneously in situ in the immobilized group and in
      its contralateral control, and in the sham-immobilized group and in its
      contralateral control. Muscle fiber and endplate morphologies were determined by
      histochemical methods; membrane acetylcholine receptors (AChRs) were determined
      by 125I alpha-bungarotoxin assay; and the level of expression of AChR subunit
      transcripts was determined by reverse transcriptase-polymerase chain reaction.
      Immobilization reduced Pt, Po, fatigability, muscle mass, and fiber cross
      sectional area (p<.001 vs. controls), but did not decrease tension per unit
      muscle mass, fiber oxidative capacity, or motor endplate size. Muscle mass
      correlated with fiber cross-sectional area. Changes in fiber cross-sectional area
      accounted for 23% and 46% (p< or =.043) of the variability in Pt and Po,
      respectively. Pt and Po correlated poorly with total AChR protein and expression
      of epsilon- and gamma-subunit messenger RNA. CONCLUSION: To the extent that the
      immobilization model simulates the disuse-induced muscle dysfunction of critical
      illness, the results suggest that disuse per se may contribute to the muscle
      weakness, and that the muscle weakness is explained, almost exclusively, by the
      fiber atrophy and not by the qualitative or quantitative changes in AChR
      expression.

PMID- 10075051
TI  - Effects of epinephrine and amrinone on contractility and cyclic adenosine
      monophosphate generation of tumor necrosis factor alpha-exposed cardiac myocytes.
AB  - OBJECTIVE: This study utilized an in vitro neonatal rat cardiac myocyte assay to
      evaluate potential differences in the response of TNF-alpha-exposed myocytes to
      stimulation with the adrenergic agent, epinephrine, and the phosphodiesterase III
      inhibitor, amrinone. DESIGN: Contractility was assessed by measuring the maximum
      extent of the contraction of electrically paced neonatal rat cardiac myocytes in
      tissue culture using a closed-loop video tracking system. Myocytes were incubated
      in control or media containing TNF-alpha (50 ng/mL) for 20 mins and were then
      stimulated with increasing concentrations of either epinephrine (0.1 to 100
      ng/mL) for 15 mins or amrinone lactate (0.25 to 10 microg/mL) for 20 mins.
      MEASUREMENTS AND MAIN RESULTS: Compared with control myocytes, TNF-alpha-exposed
      myocytes stimulated with increasing concentrations of epinephrine demonstrated a
      decreased peak augmentation of contractility (p<.0001 analysis of variance). This
      decrease was paralleled by a decrease in epinephrine-stimulated generation of
      cyclic AMP, as measured by enzyme-linked immunoassay (p = .05 polynomial
      regression). In contrast, increasing concentrations of amrinone produced
      increased peak augmentation of contractility (p = .003 analysis of variance) in
      TNF-alpha-exposed cardiac myocytes (relative to controls). However, this increase
      was not reflected by increased amrinone-stimulated generation of cyclic AMP
      relative to control myocytes not exposed to TNF-alpha (p = NS polynomial
      regression). CONCLUSIONS: Our data suggest that TNF-alpha induces a defect in
      beta-adrenergic signal transduction and catecholamine-stimulated contractility in
      neonatal rat cardiac myocytes. In addition, TNF-alpha augments the inotropic
      response of myocardial tissue to phosphodiesterase inhibitors through a mechanism
      independent of cyclic AMP generation. Phosphodiesterase inhibitors such as
      amrinone may be found to exert significant inotropic effects in catecholamine
      refractory septic shock with myocardial depression and other conditions of
      inflammatory myocardial dysfunction.

PMID- 10075052
TI  - Evaluation of a new continuous thermodilution cardiac output monitor in cardiac
      surgical patients: a prospective criterion standard study.
AB  - OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor in
      critically ill patients. DESIGN: Criterion standard study. SETTING: Cardiac
      surgery intensive care unit in a university hospital. PATIENTS: Twenty cardiac
      surgical patients requiring intensive care treatment with pulmonary artery
      catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Cardiac output was monitored continuously with a modified pulmonary artery
      catheter that has a heating filament on the outside of the catheter. Four modes
      of data processing with different response times ("Normal," "Fast," "FastFilter,"
      and "Urgent" modes) used by the monitoring system. A total of 240 determinations
      of cardiac output were performed using conventional bolus thermodilution
      technique; these results were compared with those obtained using three of the
      four continuous measuring modes available ("Normal," "FastFilter," and "Urgent").
      Cardiac output ranged from 3.47 to 15.77 L/min (bolus thermodilution). The mean
      (bias) +/- SD of differences (precision) for all measurements was 0.40+/-1.26
      L/min in the Normal mode (cardiac output <10 L/min: 0.34+/-0.66 L/min), 0.53+/
      1.27 L/min in the FastFilter-mode (cardiac output <10 L/min: 0.60+/-0.75 L/min),
      and 0.63+/-1.34 L/min in the Urgent mode (cardiac output <10 L/min: 0.57+/-0.82
      L/min). CONCLUSIONS: Continuous cardiac output measurement using the
      thermodilution technique is reasonably accurate, reliable, and applicable in
      routine clinical practice. The values obtained using the Normal mode of the
      monitor agreed significantly better with the conventional thermodilution method
      than the results of the two other modes studied (FastFilter and Urgent). In
      addition, measurements in two patients with cardiac output values of >10 L/min
      did not agree with the results of the bolus thermodilution method.

PMID- 10075053
TI  - The relationship of pre mortem diagnoses and post mortem findings in a surgical
      intensive care unit.
AB  - OBJECTIVE: To evaluate pre- and post mortem diagnoses and determine their
      relationship and the discrepancy rate. DESIGN: Retrospective, descriptive chart
      review. SETTING: A 36-bed surgical intensive care unit (ICU) of an academic,
      tertiary care center. PATIENTS: 149 adults who died in the ICU and had an post
      mortem examination. INTERVENTIONS: Review of the medical record for the ICU
      course, hospital discharge/death summary, major and minor clinical diagnoses, and
      the cause of death were directly compared with the major and minor diagnoses and
      cause(s) of death determined by post mortem examination. MEASUREMENTS AND MAIN
      RESULTS: Major and minor clinical diagnoses were categorized by the Goldman
      method and compared with post mortem findings to determine the discrepancy rate.
      Patients were categorized by the primary surgical service that provided medical
      and surgical care. Sixty-one (41%) patients had discrepancies uncovered at post
      mortem examination, of which 20 had two discrepancies. Twenty-three percent of
      the 149 patients had errors categorized as major and 18% as minor. Overall, 85%
      of the major errors were undiagnosed infectious processes. Complete agreement
      between the pre and post mortem diagnoses was present in 58% and varied with the
      surgical population: trauma group (86%) and cardiac surgery (69%) vs. the
      transplantation group (17%). Those with longer lengths of stay in the ICU were
      more likely to develop and, subsequently, have a major error discovered post
      mortem. Conversely, those who died early (<48 hrs), were less likely to have an
      undiagnosed disease at post mortem examination and, thus, more likely to have
      complete agreement between pre and post mortem findings. CONCLUSIONS: The overall
      discrepancy rate as well as the infectious discrepancy rate between pre mortem
      clinical diagnoses and post mortem findings were substantially higher in a
      surgical ICU compared with a hospital-wide population. The majority of these
      discrepancies were undiagnosed infections. The length of time spent in the ICU
      before death appeared to influence the rate of errors uncovered at the post
      mortem examination, suggesting that a longer ICU course, as well as the
      particular type of surgical patient population, may increase the chance of
      developing an infectious process, only to be uncovered at post mortem
      examination.

PMID- 10075054
TI  - The alveolar space is the site of intense inflammatory and profibrotic reactions
      in the early phase of acute respiratory distress syndrome.
AB  - OBJECTIVES: To determine the concentrations of proinflammatory mediators,
      collagenases, and procollagen type III peptides in undiluted pulmonary edema
      fluids and in plasma obtained in patients with early acute respiratory distress
      syndrome (ARDS) and in control patients with hydrostatic lung edema; and to
      assess the relationship between these inflammatory and profibrotic markers.
      DESIGN: A prospective, clinical study with measurements of inflammatory markers
      in pulmonary edema fluids and in paired plasma samples. SETTING: A medical
      intensive care unit. PATIENTS: Patients intubated with lung permeability (n = 23)
      and hydrostatic (n = 8) pulmonary edema were prospectively enrolled in the study.
      The severity of the disease at the time of intubation was assessed, using the
      Simplified Acute Physiological Score (SAPS) II and the Lung Injury Score (LIS).
      INTERVENTIONS: Plasma and undiluted edema fluids were obtained at the time of
      intubation with pulmonary edema requiring mechanical ventilation; and in some
      patients, a second edema fluid sample was collected a few hours later.
      MEASUREMENTS AND MAIN RESULTS: Proinflammatory activity, dependent on the
      presence of bioactive proinflammatory cytokines, interleukin (IL)-8, and
      neutrophil matrix metalloproteinase (MMP)-9 were significantly increased in ARDS
      fluids compared with plasma or control fluids from patients with congestive heart
      failure. In contrast, MMP-2, originating from lung cells other than phagocytes,
      was slightly increased in ARDS edema fluids compared with plasma, but similar to
      levels found in hydrostatic edema fluids. Proinflammatory activity was
      undetectable in plasma from ARDS patients. Levels of procollagen peptide III, a
      marker of collagen synthesis, were increased in permeability edema fluids
      compared with hydrostatic edema fluids or plasma, confirming that alveolar
      collagen synthesis begins very early and in parallel with acute inflammation in
      ARDS. Control patients with hydrostatic edema had similar SAPS II and LIS scores
      compared with ARDS patients. CONCLUSIONS: These results strongly support the
      conclusion that during the early phase of ARDS, the lung is the site of an
      intense inflammatory process with sequential activation of cytokines, chemokines,
      and secretion of proteases, as well as concomitant collagen synthesis. The
      inflammation is mostly limited to the lung, with low levels of inflammatory
      mediators in the systemic circulation. Unlike clinical scoring systems (SAPS II
      and LIS), inflammatory markers differentiate patients with permeability and
      hydrostatic pulmonary edema.

PMID- 10075055
TI  - The extent of traumatic damage determines a graded depression of the endotoxin
      responsiveness of peripheral blood mononuclear cells from patients with blunt
      injuries.
AB  - OBJECTIVE: To study whether the endotoxin responsiveness of peripheral blood
      mononuclear cells correlates with the severity of injury in trauma patients.
      DESIGN: Prospective, observational study. SETTING: University trauma center.
      PATIENTS: Fifty-nine patients with blunt trauma (Injury Severity Score [ISS] 4 to
      57 points). INTERVENTIONS: Standard emergency department care, surgical care, and
      postoperative intensive care unit treatment. MEASUREMENTS AND MAIN RESULTS: Whole
      blood and serum were obtained 94+/-89 (SD) mins post trauma (day 0) and during a
      14-day period postinjury. Endotoxin-induced tumor necrosis factor-alpha (TNF
      alpha) synthesis of peripheral blood mononuclear cells ex vivo was tested using a
      whole blood assay. Serum samples were assayed for TNF-alpha concentrations. A
      reduced capacity of whole blood to produce TNF-alpha ex vivo with endotoxin
      treatment was found to be closely correlated with the ISS. The capacity to
      produce TNF-alpha on endotoxin stimulation of whole blood from patients with an
      ISS > or =16 points was depressed immediately after trauma and did not reach
      normal values during the observation period. In patients with an ISS >22 points,
      maximum depression of the capacity of whole blood to produce TNF-alpha occurs
      within 100 mins post injury. In contrast, in patients with an ISS <22 points,
      maximal depression of whole blood TNF-alpha production occurs with a delay of 24
      to 48 hrs after trauma. Based on pre- and postoperative values, primary surgical
      intervention caused a decrease of the endotoxin-stimulated TNF-alpha production
      of whole blood in the latter patient subgroup, as well as in the entire patient
      population (ISS 4 to 57) when secondary surgical treatment was necessary 5 to 13
      days after trauma. CONCLUSIONS: The extent of traumatic tissue damage leads to a
      graded depression of immunocyte function and appears to be amplified by surgical
      treatment. The endotoxin responsiveness of peripheral blood mononuclear cells
      displays a functional marker of the anatomically defined severity of injury and
      gives insights into the regulation of immunocyte function after severe blunt
      trauma.

PMID- 10075056
TI  - Differential expression of tumor necrosis factor receptor subtypes on leukocytes
      in systemic inflammatory response syndrome.
AB  - OBJECTIVE: To determine the expression of tumor necrosis factor (TNF) receptor in
      patients with systemic inflammatory response syndrome (SIRS). DESIGN: Prospective
      study. SETTING: Intensive care unit and central laboratory. PATIENTS: Blood
      specimens from 18 healthy volunteers (controls) and 16 patients with SIRS.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using monoclonal antibodies,
      fluorescence labeling, and high sensitivity flow cytometry, we measured the
      expression of membrane TNF receptor subtypes TNF-R55 and TNF-R75 on peripheral
      blood leukocytes. Receptor expression is expressed as mean fluorescence intensity
      +/- SD (units: detection channel number). In controls, TNF-R55 was only weakly
      expressed (monocytes: 2.5+/-1.8; neutrophils: 0.7+/-0.8), whereas expression of
      TNF-R75 was higher (monocytes: 28.6+/-9.0; neutrophils: 4.8+/-1.0) and was also
      found on lymphocytes (on CD8+ lymphocytes: 5.7+/-1.8; CD16+: 5.5+/-1.2; CD4+:
      9.7+/-3.7). In SIRS, we observed increased expression of TNF-R55 on monocytes
      (6.9+/-3.4, p<.001) and neutrophils (2.2+/-1.9, p<.01), as well as decreased
      expression of TNF-R75 on monocytes (17.3+/-13.2; p<.001). The extent of TNF-R55
      up-regulation did not correlate with that of TNF-R75 down-regulation. TNF-R55 on
      monocytes and neutrophils strongly correlated with body temperature but not with
      survival, whereas monocyte TNF-R75 was considerably lower in nonsurvivors, albeit
      not significantly (12.3+/-7.1 vs. 23.9+/-16.7; p = .07). CONCLUSIONS: These data
      indicate that leukocyte TNF-R55 and TNF-R75 react differentially and probably
      serve different functions in SIRS, which prompts the investigation of receptor
      subtype-specific therapeutic approaches.

PMID- 10075057
TI  - Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic
      oxygen kinetics and metabolic activity in septic shock.
AB  - OBJECTIVE: To investigate the impact of exogenous beta-adrenergic receptor
      stimulation on splanchnic blood flow, oxygen kinetics, glucose-precursor flux,
      and liver metabolism in septic shock. DESIGN: Prospective trial. SETTING:
      University hospital intensive care unit. PATIENTS: Six patients with hyperdynamic
      (cardiac index >4.0 L/min/m2) septic shock, all requiring norepinephrine to
      maintain blood pressure >65 mm Hg. INTERVENTIONS: We compared norepinephrine and
      phenylephrine titrated to achieve similar systemic hemodynamics and gas exchange.
      Splanchnic hemodynamics, oxygen kinetics, and metabolic parameters were measured
      before, during, and after replacing norepinephrine with phenylephrine.
      MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and oxygen kinetics were
      derived from the steady-state indocyanine-green clearance based on hepatic dye
      extraction and arterial and hepatic venous blood gases. Endogenous glucose
      production rate was derived from the plasma appearance rate of stable-isotope
      labeled glucose using a primed-constant infusion. Splanchnic lactate, alanine
      (high-performance liquid chromatography) uptake, and hepatic
      monoethylglycinexylidide (MEGX) (fluorescence polarization immunoassay) formation
      rates were calculated from splanchnic blood flow and arterial-hepatic venous
      concentration differences. Replacing norepinephrine with phenylephrine induced no
      change in systemic hemodynamics or gas exchange. While splanchnic oxygen
      consumption and alanine uptake rate remained unaffected, splanchnic blood flow,
      oxygen delivery, and lactate uptake rate were significantly decreased. Glucose
      production rate also decreased significantly. A return to norepinephrine restored
      splanchnic blood flow, oxygen delivery, and lactate uptake rate to baseline
      values, while glucose production rate remained depressed. Hepatic MEGX formation
      rate was not influenced during the investigation. CONCLUSIONS: Exogenous beta
      adrenergic receptor stimulation determines splanchnic blood flow, oxygen
      delivery, and glucose precursor flux but not splanchnic oxygen utilization in
      septic shock. Gluconeogenesis is not directly affiliated to hepatosplanchnic
      oxygen kinetics. The different response of glucose and MEGX production rates,
      metabolic pathways of the periportal and perivenous region, may document
      intrahepatic heterogeneity associated with hepatocellular metabolic
      compartmentation.

PMID- 10075058
TI  - Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous
      verapamil infusion: clinical experience in the intensive care unit.
AB  - OBJECTIVE: Our study aimed at evaluating the pharmacokinetic, cardiovascular, and
      metabolic effects of high-dose verapamil continuous intravenous infusion in
      cancer patients. DESIGN: Prospective clinical and pharmacokinetic study. SETTING:
      Intensive care unit of a Cancer Research Institute. PATIENTS: Nine patients (age
      range 31 to 57 yrs) with progressive cancer disease and without cardiovascular,
      renal, or hepatic dysfunctions. INTERVENTIONS: After a loading dose (0.15 mg/kg
      followed by 12 hrs of continuous intravenous infusion at 0.20 mg/kg/hr), the
      infusion rate of verapamil was increased every 24 hrs (0.25, 0.30, 0.35, and 0.40
      mg/kg/hr). The highest rate was maintained for 48 hrs. Doxorubicin was given from
      the 60 th to the 108 th hr. Hydrochlorothiazide (25 mg/day) and potassium (36
      mmol/day) were given orally. Altogether, 17 courses were completed. MEASUREMENTS
      AND MAIN RESULTS: Steady state concentration (C(SS) and systemic clearance of
      verapamil and nor-verapamil (active metabolite) for each infusion rate were
      calculated. Mean arterial pressure (MAP), central venous pressure (CVP), heart
      rate (HR), PR, QT and QTc intervals, and left ventricular ejection fraction
      (LVEF) were measured, as well as daily body weight, blood glucose and potassium.
      C(SS) of verapamil and nor-verapamil increased more than proportionally to the
      infusion rate (p<.001). Systemic clearance of verapamil decreased over the range
      of the infusion rate (p<.005). MAP and HR decreased at the 12th hr (p<.001) and
      then plateaued. CVP increased (p<.01). The relationship between MAP, HR, CVP, and
      verapamil plasma concentrations was significant (r2 = .25, .14, and .35,
      respectively; p<.0001). LVEF did not change. Six patients (11 courses) developed
      junctional rhythm. Three patients (six courses) showed a PR interval increase
      (p<.05). Patients with junctional rhythm had higher Css of verapamil (p<.009).
      Overall, QT and QTc intervals increased (p<.01). A linear relationship was
      observed between verapamil plasma concentrations and QT intervals (r2 = .09,
      p<.01). Cardiovascular side effects did not determine treatment withdrawal in any
      patient. Body weight, blood glucose, and potassium did not show significant
      changes. CONCLUSIONS: Our data suggest a capacity-limited clearance of high-dose
      verapamil. In the absence of heart disease, following a step by step increase of
      the dosage, the high plasma verapamil concentrations (617 to 2970 ng/mL) produce
      frequent but well tolerated hemodynamic and electrocardiogram changes.

PMID- 10075059
TI  - Perioperative predictors of extubation failure and the effect on clinical outcome
      after cardiac surgery.
AB  - OBJECTIVES: To determine perioperative predictors of extubation failure
      (requirement for reintubation and mechanical ventilation after prior successful
      weaning from ventilator support and extubation) after cardiac surgery and the
      effect on clinical outcome. DESIGN: Cohort study. SETTING: A tertiary-care, 54
      bed, cardiothoracic intensive care unit (ICU). PATIENTS: ICU admissions (n =
      11,330) after cardiac surgery over a 42-month period. INTERVENTIONS: Collection
      of preoperative, operative, and ICU data from a database. MEASUREMENTS AND MAIN
      RESULTS: Frequency of extubation failure, total duration of mechanical
      ventilation, length of stay in ICU and hospital, and death. There were 748 (6.6%)
      patients who were weaned from mechanical ventilation after cardiac surgery and
      required reintubation and ventilator support. The predictors of extubation
      failure were: age of > or =65 yrs; inpatient hospitalization before surgery;
      arterial vascular disease; chronic obstructive pulmonary disease; pulmonary
      hypertension; severe left ventricular dysfunction; cardiac shock; hematocrit of <
      or =34%; blood urea nitrogen of > or =24 mg/dL; serum albumin concentration of <
      or =4.0 g/dL (< or =40.0 g/ L); systemic oxygen delivery of < or =320 mL/min/m2;
      redo operation; surgical procedures involving the thoracic aorta; transfusion of
      blood products of > or =10 units; and cardiopulmonary bypass time of > or =120
      mins. Extubation failure prolonged the length of total mechanical ventilation, as
      well as ICU and hospital stay, independent of the frequency of organ dysfunction
      or nosocomial infections but did not increase the risk of death after cardiac
      surgery. CONCLUSIONS: Extubation failure after cardiac surgery is uncommon.
      Although extubation failure increased the utilization of ICU and hospital
      resources, it did not affect mortality after cardiac surgery. Protocols for early
      extubation and ICU discharge should be modified in the presence of certain
      preoperative and operative predictors of extubation failure to avoid unnecessary
      increase in the cost of care after cardiac surgery.

PMID- 10075060
TI  - Meconium and amniotic fluid embolism: effects on coagulation in pregnant mini
      pigs.
AB  - OBJECTIVE: A hallmark of amniotic fluid embolism is the induction of coagulation
      defects. Little is known about the nature of these defects or the causative agent
      or agents. The purpose of this study was to assess the effects of meconium
      containing (native) meconium-amniotic-fluid infusion (MAFI) and meconium-free
      (centrifuged) amniotic-fluid infusion (AFI) on the coagulation system in the mini
      pig model. DESIGN: Laboratory study. SETTING: University institute animal
      laboratory. SUBJECTS: Near-term pregnant Gottingen bred mini-pigs in three groups
      (control, MAFI, AFI) of six animals each. INTERVENTIONS: After induction of
      anesthesia, amniotic fluid was collected by cesarean section in all animals.
      Depending on the group, animals received either Ringer's solution (control),
      native amniotic fluid (MAFI), or centrifuged amniotic fluid (AFI) via an ear
      vein. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from a central vein
      before infusion (baseline), immediately after infusion, every 10 mins until 90
      mins after infusion, and finally, every 20 mins until 150 mins after infusion.
      The following parameters were measured: Platelets, partial thromboplastin time,
      prothrombin time, fibrinogen, factors V, VII, VIII, antithrombin III, and protein
      C. The values relative to baseline in the MAFI and AFI groups were compared with
      control by rank order test. A p<.05 was considered statistically significant.
      Compared with the control group, platelets were lower in the MAFI group (p<.005),
      PTT was prolonged in both the MAFI and AFI groups (p<.005), fibrinogen was lower
      in both the MAFI and AFI groups (p<.05), prothrombin index was lower (i.e.,
      prothrombin time was prolonged) in the MAFI group (p<.05), and protein C was
      lower in the MAFI group (p<.005). CONCLUSIONS: Both MAFI and, to a much lesser
      extent, AFI cause an activation of coagulation in mini-pigs. The changes induced
      by meconium-free AFI are probably not sufficient to explain the high mortality of
      the condition.

PMID- 10075061
TI  - Roles of nitric oxide synthases in platelet-activating factor-induced intestinal
      necrosis in rats.
AB  - OBJECTIVE: To examine the role of constitutive and inducible nitric oxide
      synthases (cNOS and iNOS) in platelet-activating factor (PAF)-induced shock and
      intestinal injury. DESIGN: Prospective, randomized, controlled experimental
      study. SETTING: Hospital research laboratory. SUBJECTS: Young adult male Sprague
      Dawley rats were anesthetized and studied. INTERVENTIONS: Rats were injected with
      PAF, either alone or after the following pretreatments: a) selective iNOS
      inhibitors aminoguanidine or S-methylisothiourea; b) 3-morpholinosydnonimine, a
      NO donor; c) S-methylisothiourea + 3-morpholinosydnonimine; and d) antineutrophil
      antibody (to deplete neutrophils). MEASUREMENTS AND MAIN RESULTS: Blood pressure,
      hematocrit, white blood cell counts, intestinal injury, and intestinal cNOS and
      iNOS activities were assessed. We found that: a) cNOS is the predominant NOS in
      the intestine and its activity is inversely correlated to the level of tissue
      injury; b) there is a time-dependent increase in cNOS activity in sham-operated
      animals, which was abolished by PAF; c) Western blotting and immunohistochemistry
      showed iNOS present in the normal intestine, localizing mainly in crypt cells; d)
      iNOS inhibitors attenuated PAF-induced injury in animals with high cNOS activity,
      but had no protective effect in animals with low cNOS activity; e) 3
      morpholinosydnonimine, alone or together with S-methylisothiourea, alleviated PAF
      induced injury; and f) neutrophil depletion blocked the suppressive effect of PAF
      on cNOS and prevented injury. CONCLUSIONS: We conclude that cNOS and iNOS play
      different roles in PAF-induced intestinal injury. Caution should be exerted
      concerning potential therapeutic uses of iNOS inhibitors.

PMID- 10075062
TI  - Effects of adrenergic-receptor blockade and ligation of spleen vessels on the
      hemodynamics of dogs injected with scorpion venom.
AB  - OBJECTIVE: In dogs, scorpion venom evokes a rapid increase in cardiac output (CO)
      that decreases below baseline level in 1 hr. The changes in CO have recently been
      shown to be related to the effect of the venom on venous return. In the present
      study, we tested the hypothesis that changes in determinants of venous return are
      secondary to sympathoadrenal stimulation evoked by the venom, which causes
      splenic contracture in the first stage of envenomation leading to increased mean
      circulatory pressure (MCP) and CO. Persistence of adrenergic response is the main
      factor leading to the second stage of envenomation, characterized by an increase
      in resistance to venous return (Rv) and a decrease in CO. DESIGN: Repeated
      measures, prospective study in dogs. SETTING: University-affiliated research
      laboratory. SUBJECTS: Mixed-breed dogs injected with scorpion venom.
      INTERVENTIONS: The effects of alpha- and beta-adrenergic-receptor blockade
      (blockade group, n = 9 dogs) and effects of ligation of spleen vessels (spleen
      ligation group, n = 11 dogs) following intravenous injection of scorpion venom
      from Leiurus quinquestriatus (0.05 mg/kg) were tested on the determinants of
      venous return and compared with the effects of scorpion venom alone (control
      group, n = 6 dogs). MEASUREMENTS AND MAIN RESULTS: Scorpion venom in the control
      group caused a marked increase in CO from 2.9+/-0.2 SD L/min to 6.5+/-2.2 L/min
      (p<.001) and MCP from 8.7+/-2.7 torr (1.2+/-0.35 kPa) to 21.6+/-1.4 torr (2.9+/
      0.19 kPa) (p<.001) within 5 mins after venom injection. Cardiac output and MCP
      markedly decreased at 60 mins to 1.8+/-0.3 L/min (p<.001) and 7.3+/-3.8 torr
      (1.0+/-0.5 kPa) (p<.05), respectively. Rv did not change at 5 mins but increased
      from 196+/-50 dyne x sec/cm5 to 335+/-102 dyne x sec/cm5 (p<.01) at 60 mins.
      Adrenergic-receptor blockade attenuated the increase of CO and MCP at 5 mins,
      from 2.1+/-0.5 L/min to 2.7+/-1 L/min (p<.001) and from 5.6+/-2.0 torr (0.8+/
      0.27 kPa) to 7.5+/-2.3 torr (1.0+/-0.31 kPa) (p<.05), respectively. By 60 mins,
      both CO and MCP returned to baseline, while Rv was not affected and was
      maintained at 204+/-158 dyne x sec/cm5. Ligation of spleen vessels prevented a CO
      increase at 5 mins and it was maintained at baseline value (2.5+/-0.6 L/min).
      However, MCP increased from 7.9+/-0.5 torr to 12+/-1.3 torr (p<.05). At 60 mins,
      CO decreased to 1.6+/-0.7 L/min (p<.01) while MCP returned to baseline. The
      changes in MCP were accompanied by significant increases of Rv from 152+/-24 dyne
      x sec/cm5 to 383+/-93 dyne x sec/cm5 (p<.001) at 5 mins, and 510+/-175 dyne x
      sec/cm5 (p<.01) at 60 mins. CONCLUSIONS: The changes in CO and MCP following
      scorpion venom injection in dogs are in part related to sympathetic stimulation.
      Adrenergic-receptor blockade attenuated the initial inotropic effect of the venom
      and completely prevented a late decrease in CO and MCP. The increase in Rv is the
      most important factor for late decrease in CO, and results from persistent
      adrenergic-receptor stimulation. In addition, an Rv increase apparently expresses
      vasoconstriction and redistribution of blood flow. The initial increase in CO and
      MCP is explained mainly by adrenergic-receptor effects on the spleen leading to
      augmented circulatory blood volume.

PMID- 10075063
TI  - Enteral infusion of sodium 2-ketoisocaproate in endotoxic rats.
AB  - OBJECTIVE: In view of our previous finding that the intravenous infusion of 2
      ketoisocaproate (KIC) improved survival in septic rats, we endeavored to
      determine whether the enteral infusion of KIC improves survival in endotoxic
      rats, and, if so, the mechanism of this effect. SUBJECTS: Eighty-five rats were
      given 15 mg/kg of Escherichia coli lipopolysaccharide (026:B6). INTERVENTIONS:
      KIC, sodium pyruvate (PYR), or sodium bicarbonate (HCO3) was infused continuously
      intragastrically at 18.75 mmol/kg/day. MEASUREMENTS AND MAIN RESULTS: KIC
      administration increased circulating concentrations of KIC and ketone bodies.
      Survival rates were: KIC 17/32; PYR 2/22; and HCO3 8/31. The significant
      improvement in survival with KIC, in contrast with HCO3 (p<.04) or PYR (p<.002),
      points to an effect specific to KIC rather than to ketoacids generally, and
      argues against an antioxidant mechanism to explain improved survival with enteral
      administration. To determine whether altered nitric oxide production was
      responsible, plasma nitrite plus nitrate concentrations were measured
      sequentially in rats given a lower dose of lipopolysaccharide plus continuous
      intragastric KIC, PYR, or HCO3. All rats exhibited pronounced increases in plasma
      nitrite plus nitrate concentrations, peaking at 8 hrs, but both KIC and PYR
      caused greater increases than HCO3. Thus, differences in nitric oxide production
      cannot account for the different effects of PYR and KIC on survival. However, KIC
      infusion for 8 hrs substantially increased ketone bodies in blood and liver, in
      comparison with the infusion of HCO3 or PYR. CONCLUSION: Continuous enteral
      infusion of KIC improves survival in endotoxemia, probably by its conversion to
      ketone bodies, which serve as an alternative energy substrate.

PMID- 10075064
TI  - Immediate application of positive-end expiratory pressure is more effective than
      delayed positive-end expiratory pressure to reduce extravascular lung water.
AB  - OBJECTIVE: To determine by the measurement of extravascular lung water (EVLW)
      whether the timing of positive-end expiratory pressure (PEEP) application
      influences the intensity of lung injury. DESIGN: Animal experimental study.
      SETTING: Animal experimental laboratory. SUBJECTS: Mixed-breed pigs (n = 18),
      aged 4 to 5 mos, weighing 25 to 30 kg. INTERVENTIONS: The animals were
      anesthetized and tracheotomized, after which a permeability pulmonary edema was
      instigated by infusing oleic acid (0.1/kg) into the central vein. All animals
      were then randomly divided into three groups. In group 1 (n = 5), 10 cm H2O of
      PEEP was applied immediately after the oleic acid infusion and maintained
      throughout the 6 hrs of the experiment. Group 2 (n = 7) received the same level
      of PEEP 120 mins after the insult for 4 hrs. Group 3 (n = 6), the control group,
      was ventilated without PEEP for the six hrs of the experiment. MEASUREMENTS AND
      MAIN RESULTS: At the end of the experiment, EVLW was calculated by gravimetric
      method. EVLW in group 1 (11.46+/-2.00 mL/kg) was significantly less than in group
      2 (19.12+/-2.62 mL/kg) and group 3 (25.81+/-1.57 mL/kg), (p<.0001). Oxygenation
      also showed important differences by the end of the experiment when the Pao2/Fio2
      ratio was significantly better in group 1 (467+/-73) than in group 2 (180+/-82)
      and group 3 (39+/-9), (p<.0001). CONCLUSIONS: The application of 10 cm H2O of
      PEEP reduces EVLW in a time-dependent manner and maximum protective effect is
      achieved if it is applied immediately after lung injury production.

PMID- 10075065
TI  - Porcine endotoxemic shock is associated with increased expired nitric oxide.
AB  - OBJECTIVES: Nitric oxide (NO) is believed to decrease systemic vascular
      resistance in sepsis, but the data are mainly from studies on rats and mice. We
      tested this hypothesis in pigs and also whether there is induction of the
      inducible form of nitric oxide synthase (iNOS). DESIGN: Animal study. SETTING:
      University center. SUBJECTS: Ten pigs. INTERVENTIONS: The pigs were anesthetized
      and mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: Pulmonary and
      systemic hemodynamics were monitored and mixed expired NO was measured by
      chemiluminescence. Animals received 20 microg/kg of endotoxin over 2 hrs. We then
      infused 25 mg/kg of N(omega)-nitro-L-arginine methyl ester (L-NAME) over 10 mins,
      followed by 0.5 g/kg of L-arginine, the precursor of NO, for 30 mins more to
      reverse the effects of L-NAME. Five additional pigs were treated with 20
      microg/kg of endotoxin for 2 hrs and followed for another hour. Plasma
      nitrite/nitrate was measured by Greiss reaction. The animals were then killed and
      tissues were sampled for iNOS by Western blot, and iNOS messenger RNA by reverse
      transcriptase polymerase chain reaction. After endotoxin infusion, arterial
      pressure (BP) initially increased, then decreased to 62+/-1 mm Hg from the
      baseline of 115+/-4 mm Hg (p<.001). Cardiac output initially decreased, then
      increased slightly from the baseline of 3.7+/-0.2 to 4.2 +/-0.3 L/min (p<.05).
      The BP pattern was mirrored by an increase in expired NO concentration from 6.4+/
      0.8 to 10.4+/-1.4 parts per billion (p<.05) and increased rate of pulmonary NO
      excretion in expired gas (VeNO) from 71+/-10 to 146+/-24 pmol/kg/min (p<.05).
      Inhibition of NOS with L-NAME decreased expired NO concentration and VeNO and
      increased BP; however, cardiac output decreased. The vasoconstriction produced by
      L-NAME was partially reversed by L-arginine, and this also increased VeNO from
      80+/-18 after L-NAME to 132+/-31 pmol/kg/min (p<.05). Plasma nitrite (n = 5) did
      not change and there was no iNOS by Western blot analysis in multiple tissues.
      However, there was a small increase in messenger RNA by reverse transcriptase
      polymerase chain reaction. CONCLUSIONS: The time course and pattern of changes in
      expired NO during endotoxemia followed the change in systemic hemodynamics, which
      supports a causal role for NO in sepsis. However, this is not due to a large
      production of NO by iNOS induction. The hemodynamic pattern, nitrite in blood,
      and changes in expired NO also differed markedly from those findings in rodent
      models and caution should be used in extrapolating from rodents to higher order
      animals.

PMID- 10075066
TI  - Dopexamine attenuates flow motion in ileal mucosal arterioles in normotensive
      sepsis.
AB  - OBJECTIVES: Injury to the small intestine is thought to play a crucial role in
      the development and propagation of sepsis. Cellular hypoxia, caused by
      hypoperfusion, may result in increased mucosal permeability, thus allowing the
      translocation of bacteria and endotoxin to the circulation. The purpose of this
      study was to assess the effect of the synthetic catecholamine, dopexamine, on the
      mucosal microcirculation of the septic rat ileum. DESIGN: Randomized, crossover
      study. SETTING: Teaching hospital animal laboratory. SUBJECTS: Sprague-Dawley
      male rats. INTERVENTIONS: Sepsis was induced by cecal ligation and perforation in
      11 male Sprague-Dawley rats. Six sham animals were also studied. At 24 hrs, rats
      were anaesthetized, intubated, ventilated, and prepared for intravital microscopy
      of the mucosal surface of the ileum. Dopexamine (8 microg/kg/min) and saline were
      infused intravenously into each rat using a randomized crossover design.
      MEASUREMENTS AND MAIN RESULTS: Observations were videotaped for later analysis of
      arteriolar flow patterns, red cell velocity, arteriolar diameter, and
      intercapillary area. All values are expressed as mean +/- SEM. The main effect of
      dopexamine infusion in the sepsis group was the attenuation of the rhythmic blood
      flow patterns (flow motion) observed during saline infusion. In each subject,
      dopexamine decreased the absolute number of arterioles exhibiting flow motion by
      35.93+/-6.81% (p<.001, paired t-test). Dopexamine decreased the amount of time
      red cell flow was stopped in marginal and central arterioles by 11.83+/-2.49%
      (p<.001, paired t-test). Dopexamine did not alter significantly the diameter of
      the marginal arterioles, the intercapillary area, or the red cell velocity
      compared with saline in the sepsis group. The sham group displayed marked
      microvascular differences compared with the sepsis group with respect to
      arteriolar diameter (13.32+/-0.05 vs. 9.46+/-0.24 mm, p<.001), intercapillary
      area (975.93+/-60.60 vs. 1256.03+/-43.88 mm2, p<.05 ), red cell velocity
      (611.40+/-38.77 vs. 289.15+/-36.45, p<.001), and blood flow patterns (%
      displaying flow motion, 15.89+/-6.09 vs. 58.22+/-9.63, p<.01; % time stopped
      flow, 1.96+/-0.89 vs. 20.21+/-3.92, p<.005). CONCLUSIONS: These results indicate
      that dopexamine increased overall blood flow and possibly oxygen delivery to the
      mucosa by altering patterns of blood flow within the villi. The observation that
      the diameter of the marginal arterioles is not affected by dopexamine indicates
      that dopexamine influences the mucosal microcirculation at the level of higher
      order arterioles. We conclude that sepsis results in abnormal microvascular
      villus blood flow and that dopexamine can partially restore these changes towards
      normal.

PMID- 10075067
TI  - Fasting augments lipid peroxidation during reperfusion after ischemia in the
      perfused rat liver.
AB  - OBJECTIVE: To test the hypothesis that fasting would aggravate postischemic lipid
      peroxidation in a perfused rat liver model. DESIGN: Prospective, randomized study
      in a rat perfused liver model. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS:
      Livers isolated from fed and fasted male Sprague-Dawley rats (n = 16) were
      exposed to 2.5 hrs of normothermic (38 degrees C) ischemia followed by 2 hrs of
      reperfusion. MEASUREMENTS AND MAIN RESULTS: Lipid peroxidation was measured by
      chemiluminescence and thiobarbituric acid reactive substances (TBARS). Injury
      parameters, potassium, lactate dehydrogenase efflux, and oxygen extraction were
      measured every 30 mins. Chemiluminescence and TBARS were greater in the fasted
      ischemic group during reperfusion. (fasted vs. fed: chemiluminescence, 946.8+/
      205.5 [SEM] vs. 98.1+/-8.2 counts per second, p = .0004; thiobarbituric acid
      reactive substances, 1.11+/-0.25 vs. 0.21+/-0.032 nM/g of liver wt/min, p =
      .0019). Potassium efflux in the fasted group was greater than in the fed group.
      (1.568+/-0.082 vs. 1.28+/-0.079 microEq/g liver weight/min, p = .0184). Fasted
      livers extracted less oxygen after ischemia (1.94+/-0.22 vs. 1.14+/-0.46 microM/g
      liver wt/min, p = .0048). Lactate dehydrogenase levels showed no significant
      differences. CONCLUSION: Fasting augmented lipid peroxidation markedly. Nutrition
      may be an important mechanism that protects organs from oxidative injury.

PMID- 10075068
TI  - Sufentanil, fentanyl, and alfentanil in head trauma patients: a study on cerebral
      hemodynamics.
AB  - OBJECTIVES: To determine the effects of bolus injection and infusion of
      sufentanil, alfentanil, and fentanyl on cerebral hemodynamics and
      electroencephalogram activity in patients with increased intracranial pressure
      (ICP) after severe head trauma. DESIGN: Randomized, unblended, crossover study.
      SETTING: Intensive care unit and trauma center in a university hospital.
      PATIENTS: Six patients with head trauma and ICP monitoring, sedated at the time
      of the study with propofol infusion and full neuromuscular blockade.
      INTERVENTIONS: Following a randomized order, in an unblended and crossover
      fashion, the level of sedation was deepened with a 6-min injection of either
      sufentanil (1 microg/kg), alfentanil (100 microg/kg), or fentanyl (10 microg/kg)
      followed by an infusion of 0.005, 0.7, and 0.075 microg/kg/min, respectively, for
      1 hr. The three opioids were given to each patient at 24-hr intervals.
      MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), ICP, cerebral
      perfusion pressure (CPP), and jugular vein bulb oxygen saturation (Svjo2) were
      continuously measured and recorded at 1-min intervals throughout the 60-min study
      period. Sufentanil, fentanyl, and alfentanil infusions were associated with a
      significant but transient increase in ICP (9+/-2 mm Hg [SD], 8+/-2 mm Hg, and
      5.5+/-1 mm Hg, respectively; p<.05). The increase in ICP peaked at 5, 6, and 3
      mins, respectively, then gradually decreased and returned to baseline values
      after 15 mins. This result was accompanied by a significant decrease in MAP (21+/
      2 mm Hg, 24+/-2 mm Hg, and 26+/-2 mm Hg, respectively; p<.05) and, thus, in CPP
      (30+/-3 mm Hg, 31+/-3 mm Hg, and 34+/-3 mm Hg, respectively; p<.05). After 5
      mins, MAP and CPP gradually increased, although they remained significantly
      decreased throughout the study period. No changes in lactate-oxygen index, used
      as an ischemia index, were observed. Changes in electroencephalogram tracings
      were characterized by a switch from a fast to a decreased activity, together with
      an improvement in the background activity. CONCLUSION: The results of the present
      study show that alfentanil, sufentanil, and fentanyl produce similar transient
      increases in ICP when administered by bolus injection in patients with increased
      ICP. No evidence of cerebral ischemia was observed in the study patients.

PMID- 10075069
TI  - Brain death and evoked potentials in pediatric patients.
AB  - OBJECTIVE: To define the evoked potential responses (auditory and somatosensory)
      obtained from pediatric brain-dead patients. DESIGN: Prospective study over an 8
      yr period (1988-1996). SETTING: A 14-bed pediatric intensive care unit in a
      multidisciplinary regional referral center (teaching hospital). PATIENTS: Fifty
      one pediatric patients with clinically established brain death. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Auditory brainstem and somatosensory evoked
      potentials were performed with a mean evolution time of 24 hrs after clinical
      brain death. The first brainstem auditory evoked potential recording was
      compatible with the diagnosis in 45 patients (90%): 27 patients (53%) did not
      respond, wave I was patent in 16 (7 bilateral, 6 from the left side, and 3 from
      the right side), and 2 patients evoked waves I and II in one or both ears. Gross
      anomalies were found in the remaining six patients. Sixteen patients were tested
      for somatosensory evoked potentials. N13 identifiable wave (62.5% of the
      patients) or a flat record were the obtained findings. Electric silence was noted
      initially on the electroencephalogram (EEG) in only 14 of 29 patients. Later
      flattening was observed in seven patients. Missing brainstem evoked response was
      noted earlier than cortical electric silence (range, 12-144 hrs). Any central
      wave could be pointed out in the evoked potentials of patients with an
      isoelectric EEG. CONCLUSIONS: Evoked potential is useful in confirming the
      diagnosis of brain death in infants and in children as well as in adults. The
      test can be performed at bedside without interfering with patient care, and
      results are similar to those obtained in adult patients. Flattening of the EEG
      requires more time than achieving compatible evoked-potential responses.

PMID- 10075070
TI  - A cost analysis of enterally administered lorazepam in the pediatric intensive
      care unit.
AB  - OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with
      enterally administered lorazepam in mechanically ventilated children who require
      long-term continuous sedation. DESIGN: Retrospective review of patients treated
      according to a preestablished pediatric intensive care unit (ICU) sedation
      protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's
      hospital. PATIENTS: The records of 30 mechanically ventilated children were
      analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients
      required continuous sedation for a total of 16 days (median). INTERVENTIONS:
      According to our pediatric ICU sedation protocol, midazolam infusion was
      continued until the hourly midazolam requirement was stable for at least 24 hrs.
      Thereafter, patients with a nasojejunal tube who were likely to require a minimum
      of three additional days of continuous sedation were transitioned from
      intravenous midazolam to enterally administered lorazepam. The goal in
      transitioning therapy was to titrate the lorazepam dose and reduce midazolam
      administration while maintaining an unchanged level of sedation. MEASUREMENTS AND
      MAIN RESULTS: The rate of midazolam administration was significantly (p<.05)
      reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully
      discontinued in 24 (80%) patients in 3 days (median), and adequate and
      appropriate sedation was maintained with lorazepam monotherapy. Six patients in
      whom midazolam could not be discontinued experienced a 52% reduction in the rate
      of midazolam administration as a result of adding lorazepam. Total projected
      midazolam utilization was defined as the sum of midazolam administration before
      initiating lorazepam and the projected midazolam requirement after initiating
      lorazepam. Projected midazolam cost was calculated as the product of total
      projected midazolam utilization and midazolam acquisition cost. Actual
      expenditures for both midazolam and lorazepam were subtracted from the projected
      midazolam cost to calculate the estimated cost savings. Overall, midazolam
      utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total
      projected midazolam cost for the 30 patients was $90,771. The actual cost of
      midazolam and lorazepam combined was $47,867, resulting in a cost savings of
      $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally
      administered lorazepam in critically ill children who require long-term sedation
      results in significant cost savings. The oral formulation of lorazepam was
      convenient to use, inexpensive, and effective in maintaining a continuous and
      appropriate level of sedation once midazolam was discontinued.

PMID- 10075071
TI  - Critical care services and personnel: recommendations based on a system of
      categorization into two levels of care. American College of Critical Care
      Medicine of the Society of Critical Care Medicine.
AB  - OBJECTIVES: To recommend hospital services and personnel requirements for the
      provision of optimal care to critically ill patients. Requirements for hospitals
      with comprehensive resources, as well as for hospitals with limited resources,
      are addressed. DATA SOURCES: a) Consensus opinion of critical care physicians,
      nurses, and pharmacists; and b) published guidelines of organizational and
      administrative topics addressing the provision of critical care by physicians and
      nurses, the pharmacologic approach to the critically ill patient, and diagnostic
      and laboratory testing in the management of critically ill patients. CONCLUSION:
      By combining the strengths and expertise of multidisciplinary critical care
      specialists, these guidelines provide a framework in which hospitals of varying
      resources may optimize the care of critically ill patients.

PMID- 10075072
TI  - Sepsis research: we must change course.

PMID- 10075073
TI  - Futility of randomized, controlled ARDS trials--a new approach is needed.

PMID- 10075074
TI  - Research in sepsis and acute respiratory distress syndrome: are we changing
      course?

PMID- 10075075
TI  - Allegations of sexual abuse in an intensive care unit.
AB  - OBJECTIVES: To describe misperceptions of sexual abuse by critically ill, sedated
      patients undergoing routine perineal care in an intensive care unit and to offer
      suggestions for addressing patient allegations of sexual mistreatment in this
      setting. DESIGN: Case reports and discussion. SETTING: Intermediate care unit
      extension of a medical intensive care unit at a university teaching hospital.
      PATIENTS: A 57-yr-old man who misperceived rectal intubation as sexual assault
      while receiving intravenous lorazepam for sedation; a 31-yr-old woman who
      misinterpreted a perineal bed bath as sexual abuse while receiving lorazepam and
      fentanyl. INTERVENTIONS: None. CONCLUSIONS: Under the influence of commonly used
      psychotropic drugs, some acutely ill, hospitalized patients misperceive routine
      perineal care as sexual abuse. Because the care that gives rise to mistaken
      allegations of sexual misconduct is often given in private, and because sexual
      abuse of patients sometimes actually occurs in hospitals, institutional
      investigation of these complaints is both sensitive and difficult. Some inpatient
      allegations of sexual abuse may not be resolvable by any means. Awareness of the
      potential for misinterpretation of perineal care may help prevent this disturbing
      phenomenon and promote fair, reasoned investigation when patient complaints of
      sexual abuse do arise in acute care hospitals.

PMID- 10075076
TI  - Systemic hypotension on withdrawal from inhaled nitric oxide in an adult patient
      with acute respiratory distress syndrome.

PMID- 10075077
TI  - Intensive care unit support formulations.

PMID- 10075078
TI  - Muscarinic cholinergic receptor signal transduction as a potential target for the
      developmental neurotoxicity of ethanol.
AB  - Central nervous system dysfunctions (most notably mental retardation and
      microcephaly) are among the most significant effects of in utero exposure to
      ethanol. Ethanol has been shown to cause alterations of both neuronal and glial
      cells, including cell loss, and changes in their migration and maturation. Here,
      we propose that one of the potential targets for the developmental neurotoxicity
      of ethanol may be represented by the signal transduction systems activated by
      cholinergic muscarinic receptors. Ethanol has been shown to inhibit second
      messenger systems activated by various G-protein-coupled receptors, including
      certain subtypes of muscarinic receptors. Although the roles of muscarinic
      receptors in brain development have not been fully elucidated, two potentially
      relevant effects have been discovered in the past few years. By activating
      muscarinic receptors coupled to phospholipid metabolism, acetylcholine can induce
      proliferation of glial cells, and act as a trophic factor in developing neurons
      by preventing apoptotic cell death. Ethanol has been shown to inhibit both
      actions of acetylcholine in vitro. These effects of ethanol may lead to a
      decreased number of glial cells and to a loss of neurons, which have been
      observed following in vivo alcohol exposure. In turn, these may be the basis of
      microencephaly and cognitive disturbances in children diagnosed with Fetal
      Alcohol Syndrome.

PMID- 10075079
TI  - A critical evaluation of the mechanisms of action proposed for the antitumor
      effects of the anthracycline antibiotics adriamycin and daunorubicin.
AB  - The mechanisms responsible for the antiproliferative and cytotoxic effects of the
      anthracycline antibiotics doxorubicin (Adriamycin) and daunorubicin (daunomycin)
      have been the subject of considerable controversy. This commentary addresses the
      potential role of DNA synthesis inhibition, free radical formation and lipid
      peroxidation, DNA binding and alkylation, DNA cross-linking, interference with
      DNA strand separation and helicase activity, direct membrane effects, and the
      initiation of DNA damage via the inhibition of topoisomerase II in the
      interaction of these drugs with the tumor cell. One premise underlying this
      analysis is that only studies utilizing drug concentrations that reflect the
      plasma levels in the patient after either bolus administration or continuous
      infusion are considered to reflect the basis for drug action in the clinic. The
      role of free radicals in anthracycline cardiotoxicity is also discussed.

PMID- 10075080
TI  - Inhibition and uncoupling of oxidative phosphorylation by nonsteroidal anti
      inflammatory drugs: study in mitochondria, submitochondrial particles, cells, and
      whole heart.
AB  - The effects of the anti-inflammatory drugs diclofenac, piroxicam, indomethacin,
      naproxen, nabumetone, nimesulide, and meloxicam on mitochondrial respiration, ATP
      synthesis, and membrane potential were determined. Except for nabumetone and
      naproxen, the other drugs stimulated basal and uncoupled respiration, inhibited
      ATP synthesis, and collapsed membrane potential in mitochondria incubated in the
      presence of either glutamate + malate or succinate. Plots of membrane potential
      versus ATP synthesis (or respiration) showed proportional variations in both
      parameters, induced by different concentrations of nimesulide, meloxicam,
      piroxicam, or indomethacin, but not by diclofenac. The activity of the adenine
      nucleotide translocase was blocked by diclofenac and nimesulide; diclofenac also
      slightly inhibited mitochondrial ATPase activity. Naproxen did not affect any of
      the mitochondrial parameters measured. Nabumetone inhibited respiration, ATP
      synthesis, and membrane potential in the presence of glutamate + malate, but not
      with succinate. NADH oxidation in submitochondrial particles also was inhibited
      by nabumetone. Nabumetone inhibited O2 uptake in intact cells and in whole heart,
      whereas the other five drugs stimulated respiration. These observations revealed
      that in situ mitochondria are an accessible target. Except for diclofenac, a
      negative inotropic effect on cardiac contractility was induced by the drugs. The
      data indicated that nimesulide, meloxicam, piroxicam, and indomethacin behaved as
      mitochondrial uncouplers, whereas nabumetone exerted a specific inhibition of
      site 1 of the respiratory chain. Diclofenac was an uncoupler too, but it also
      affected the adenine nucleotide translocase and the H+-ATPase.

PMID- 10075081
TI  - Cytokinetics of a novel 1,2,3-triazene-containing heterocycle, 8-nitro-3-methyl
      benzo-1,2,3,5-tetrazepin-4(3H)-one (NIME), in the human epithelial ovarian cancer
      cell line OVCAR-3.
AB  - The mechanism of action of the novel tetrazepinone 8-nitro-3-methyl-benzo-1,2,3,5
      tetrazepin-4(3H)-one (NIME), structurally related to the antitumour drug
      temozolomide, was studied in the human ovarian tumour cell line OVCAR-3. NIME
      preferentially inhibited DNA synthesis over protein and RNA syntheses at 3 and 24
      hr post-treatment. A Maxam-Gilbert sequencing assay showed that NIME induced
      barely detectable levels of guanine N7 alkylation in an isolated DNA strand, in
      contrast to temozolomide, a strong alkylating agent containing, like NIME, a
      cyclic 3-methyl-1,2,3-triazene moiety. Alkaline sucrose density-gradient
      sedimentation, at concentrations 2- to 10-fold lower than the ones used in the
      DNA sequencing assay, showed significant DNA damage in OVCAR-3 cells 24 hr after
      treatment with NIME. This was accompanied by a significant accumulation of cells
      in late S and G2M. Cell cycle arrest was transient and was reversed after 2-3
      days following drug treatment. This was in agreement with bivariate
      bromodeoxyuridine/propidium iodide analysis, which showed that at 100 microM, a
      concentration at which the majority of the cells arrested in late S and G2M, a
      significant fraction of bromodeoxyuridine positive (S-phase) cells escaped the
      block. In an attempt to elucidate the mechanism underlying these effects, the
      degradation of NIME in cell culture medium was analyzed by GC-MS (gas
      chromatography coupled with mass spectrometry). The results showed that, in
      contrast to temozolomide, NIME did not convert to an open-chain alkyltriazene in
      cell culture medium, but to a major benzimidazole product, which exerted a minor
      effect on the cell cycle. This suggests that NIME, despite containing a 3-(alkyl)
      1,2,3-triazene moiety, does not act by DNA alkylation but probably by generating
      a short-lived genotoxic species during its degradation to 6,5-benzofused
      derivatives.

PMID- 10075082
TI  - Suppression of tumor necrosis factor-activated nuclear transcription factor
      kappaB, activator protein-1, c-Jun N-terminal kinase, and apoptosis by beta
      lapachone.
AB  - Beta-lapachone, the product of a tree from South America, is known to exhibit
      various pharmacologic properties, the mechanisms of which are poorly understood.
      In the present report, we examined the effect of beta-lapachone on the tumor
      necrosis factor (TNF)-induced activation of the nuclear transcription factors NF
      kappaB and activator protein-1 (AP-1) in human myeloid U937 cells. TNF-induced NF
      kappaB activation, p65 translocation, IkappaBalpha degradation, and NF-kappaB
      dependent reporter gene expression were inhibited in cells pretreated with beta
      lapachone. Direct treatment of the p50-p65 heterodimer of NF-kappaB with beta
      lapachone had no effect on its ability to bind to the DNA. Besides myeloid cells,
      beta-lapachone was also inhibitory in T-cells and epithelial cells. Beta
      lapachone also suppressed the activation of NF-kappaB by lipopolysaccharide,
      okadaic acid, and ceramide but had no significant effect on activation by H2O2 or
      phorbol myristate acetate, indicating that its action is selective. Beta
      lapachone also abolished TNF-induced activation of AP-1, c-Jun N-terminal kinase,
      and mitogen-activated protein kinase kinase (MAPKK or MEK). TNF-induced
      cytotoxicity and activation of caspase-3 were also abolished by beta-lapachone.
      Because reducing agents (dithiothreitol and N-acetylcysteine) reversed the effect
      of beta-lapachone, it suggests the role of a critical sulfhydryl group. Overall,
      our results identify NF-kappaB, AP-1, and apoptosis as novel targets for beta
      lapachone, and this may explain some of its pharmacologic effects.

PMID- 10075083
TI  - Interaction of the transactivating protein HIV-1 tat with sulphated
      polysaccharides.
AB  - Endogenous sulphated polysaccharides such as heparin have been shown to inhibit
      the infectivity of HIV-1 min vitro. However, these naturally occurring polymers,
      due to extensive microheterogeneity within their structure, are difficult to
      characterise accurately. In contrast, dextrin can be chemically sulphated to
      produce a series of compounds sulphated in the 2-, 3-, or 6- position, or in all
      3 positions, and the use of these compounds provides an opportunity to
      investigate the anti-HIV-1 activity of sulphated polysaccharides. The mechanisms
      whereby sulphated polysaccharides exert their anti-HIV-1 activity have not been
      fully elucidated. The interaction of recombinant HIV-1 proteins with sulphated
      polysaccharides was investigated using a biotinylated derivative of dextrin 2
      sulphate (D2S) in a solid phase binding system. D2S was found to bind strongly to
      HIV-1 tat (EC50 = 0.10 microg/mL), less strongly to CD4 (EC50 = 0.33 microg/mL),
      weakly to HIV-1 vif and gp160, and not at all to HIV-1 gp120 or p24. Other
      sulphated derivatives of dextrin, i.e. dextrin 3-sulphate, dextrin 6-sulphate and
      dextrin 2,3,6-trisulphate, as well as heparin and dextran sulphate, were also
      shown to bind to HIV-1 tat, whereas the unsulphated compound dextrin did not.
      Binding studies using a series of overlapping peptides representing the complete
      sequence of HIV-1 tat revealed that D2S bound most strongly to the core domain of
      HIV-1 tat, although there was also binding to the cysteine-rich domain; both of
      these regions are important for HIV-1 tat function. In assessing function, HIV-1
      tat-mediated transactivation was measured using H938 cells, a cell line that
      contains the HIV-LTR (long terminal repeat) promoter linked to a chloramphenicol
      acetyltransferase gene. D2S significantly inhibited HIV-1 tat transactivation in
      a dose-dependent manner (IC50 = 0.5 microg/mL), whereas dextrin had no effect.
      The interaction between D2S and HIV-1 tat provides a potential mechanism of HIV-1
      inhibition whereby tat is sequestered and its transactivating activity abolished,
      effectively inhibiting the replication cycle.

PMID- 10075084
TI  - N-ethylmaleimide-stimulated arachidonic acid release in human platelets.
AB  - Treatment of human platelets with the alkylating agent N-ethylmaleimide (NEM)
      induces arachidonic acid release. The effect was time- and dose-dependent. NEM
      stimulated arachidonic acid mobilisation could be prevented by pretreating
      platelets with the cytosolic phospholipase A2 (cPLA2)-specific inhibitor
      arachidonyltrifluoromethyl ketone. Moreover, the tyrosine kinase inhibitor
      genistein was able to significantly inhibit arachidonic acid mobilisation. NEM
      stimulated release of arachidonic acid appears to be a Ca2+-dependent mechanism,
      as shown by the observation that arachidonic acid mobilisation was significantly
      reduced by platelet treatment with EGTA and abolished by preloading platelets
      with the intracellular chelator 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'
      tetraacetic acid tetra (acetoxymethyl) ester (BAPTA/AM). In Fura-2-loaded
      platelets, NEM was able to significantly increase the intracellular Ca2+ level.
      The Ca2+ elevation was significantly reduced in the presence of EGTA and
      suppressed by cell treatment with BAPTA/AM. Arachidonic acid released by NEM
      produced a significant increase in reactive oxygen species (ROS) intracellular
      levels, which was partially inhibited by diphenyleneiodonium and almost
      completely suppressed by 5,8,11,14-eicosatetraynoic acid. In conclusion, the
      results in this study demonstrate that NEM stimulates arachidonic acid release by
      cPLA2 activation through intracellular Ca2+ elevation. In addition, tyrosine
      specific protein kinases seem to be involved in arachidonic acid release. ROS was
      also shown to be formed during arachidonic acid metabolisation.

PMID- 10075085
TI  - Inhibition of [3H]thymidine incorporation into DNA of rat regenerating liver by
      2',2'-difluorodeoxycytidine coupled to lactosaminated poly-L-lysine.
AB  - The expression of asialoglycoprotein receptor (ASGP-R) on human hepatocarcinoma
      cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis
      inhibitors by their conjugation with galactosyl- terminating peptides. We
      conjugated 2',2'-difluorodeoxycytidine (dFdC), an inhibitor of DNA synthesis
      active on solid tumors, with lactosaminated poly-L-lysine (L-poly(LYS)). In
      experiments in vitro, L-poly(LYS)-dFdC inhibited proliferation of Hep G2 cells, a
      human hepatocarcinoma cell line which maintains the ASGP-R. Inhibition was
      rescued by asialofetuin. To study the pharmacological action of the conjugate in
      vivo, we used rats 18-24 hr after 2/3 hepatectomy and observed that regenerating
      hepatocytes expressed ASGP-R on their surface and internalized L-poly(LYS)-dFdC.
      Conjugate uptake by bone marrow, spleen, and intestine was negligible. We also
      found that L-poly(LYS)-dFdC inhibited [3H]thymidine incorporation into DNA of
      regenerating liver. These results indicated that hepatectomized rats were a
      suitable animal model to study the pharmacological action, on DNA-synthesizing
      hepatocytes, of conjugates binding to ASGP-R and carrying inhibitors of DNA
      synthesis. L-poly(LYS)-dFdC also inhibited [3H]thymidine incorporation in bone
      marrow, spleen, and intestine. Evidence was obtained that inhibition of DNA
      synthesis in extrahepatic tissues was a consequence of drug release from
      hepatocytes into blood-stream after the bond with the carrier has been broken
      down within liver cells. Possible ways of reducing the exit of dFdC from liver
      cells, thereby obtaining an inhibition of DNA synthesis restricted to dividing
      hepatocytes, were discussed.

PMID- 10075086
TI  - Inhibition of protein prenylation by metabolites of limonene.
AB  - The monoterpenes limonene and perillyl alcohol are undergoing clinical evaluation
      in cancer patients. In this paper, we report the chemical synthesis,
      characterisation, and quantitation in patients' plasma of a novel human
      metabolite of limonene, which is identified as an isomer of perillic acid. The
      synthesis of R-perillic acid is also described, because previous reports on the
      activity of perillic acid against isoprenylation enzymes refer to the S
      enantiomer, although it is the R-enantiomer which is the metabolite of R
      limonene. The above monoterpenes, with several related compounds, were assayed
      for inhibitory activity towards the isoprenylation enzymes in rat brain cytosol.
      Although R- and S-limonene are only weak inhibitors of the isoprenylation
      enzymes, their major metabolites, perillic acid and perillyl alcohol, are more
      potent inhibitors, with IC50 values in the low mM range. The metabolites possess
      greater activity towards the geranylgeranyltransferase type I enzyme than
      farnesyltransferase, while the novel metabolite displays IC50 values similar to
      those of perillic acid suggesting that it may contribute to the in vivo activity
      of limonene.

PMID- 10075088
TI  - Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60
      myeloid leukemia cells.
AB  - The human myeloid leukemia cell line HL-60 transports the oxidized form of
      ascorbic acid, dehydroascorbic acid (DHA), and accumulates reduced ascorbic acid.
      We studied the effect of ascorbic acid loading on apoptosis induced by serum- and
      glucose-free culture and by oxidative stress induced by H2O2. Uptake accumulation
      studies indicated that incubation of HL-60 cells with DHA resulted in the
      accumulation of intracellular ascorbic acid which decreased with time when cells
      were incubated in DHA-free medium. Exposure of HL-60 cells to increasing
      concentrations of H2O2 resulted in dose-dependent intracellular accumulation of
      peroxides, as determined by the use of the oxidation-sensitive fluorescent probe
      2',7'-dichlorofluorescin-diacetate (DCFH-DA), which was accompanied by a decrease
      in intracellular ascorbic acid and an increase in apoptosis. A dramatic decrease
      in intracellular ascorbic acid was noted when preloaded HL-60 cells were exposed
      to 150 microM H2O2 (the concentration dropped from 5.2 +/- 0.6 mM to 3.6 +/- 0.1
      mM in cells preincubated with 150 microM DHA). A dose-dependent protective effect
      of DHA was observed. Ascorbic acid loading also provided strong protection from
      apoptosis associated with serum- and glucose-free culture. Flow cytometry studies
      showed that exposure of HL-60 cells to 150 microM H2O2 resulted in decreased Bcl
      2 expression that was associated with enhanced apoptosis (up to 33.6 +/- 2.6%).
      No significant variation of Bcl-2 expression was measured following exposure of
      HL-60 cells, loaded with ascorbic acid, to 150 microM H2O2 and only a slight
      increase (up to 10.1 +/- 3.1%) in apoptosis. These findings indicate that
      ascorbic acid can inhibit apoptosis induced by oxidative stress in HL-60 cells.

PMID- 10075087
TI  - Inhibition of human prenatal biosynthesis of all-trans-retinoic acid by ethanol,
      ethanol metabolites, and products of lipid peroxidation reactions: a possible
      role for CYP2E1.
AB  - Biotransformation of all-trans-retinol (t-ROH) and all-trans-retinal (t-RAL) to
      all-trans-retinoic acid (t-RA) in human prenatal hepatic tissues (53-84
      gestational days) was investigated with HPLC using human adult hepatic tissues as
      positive controls. Catalysis of the biotransformation of t-ROH by prenatal human
      cytosolic fractions resulted in accumulation of t-RAL with minimal t-RA.
      Oxidations of t-ROH catalyzed by prenatal cytosol were supported by both NAD+ and
      NADP+, although NAD+ was a much better cofactor. In contrast, catalysis of the
      oxidation of t-RAL to t-RA appeared to be solely NAD+ dependent. Substrate Km
      values for conversions of t-ROH to t-RAL and of t-RAL to t-RA were 82.4 and 65.8
      microM, respectively. At concentrations of 10 and 90 mM, ethanol inhibited the
      conversion of t-ROH to t-RAL by 25 and 43%, respectively, but did not inhibit the
      conversion of t-RAL to t-RA significantly. In contrast, acetaldehyde reduced the
      conversion of t-RAL to t-RA by 25 and 87% at 0.1 and 10 mM respective
      concentrations. Several alcohols and aldehydes known to be generated from lipid
      peroxides also exhibited significant inhibition of t-RA biosynthesis in human
      prenatal hepatic tissues. Among the compounds tested, 4-hydroxy-2-nonenal (4-HNE)
      was highly effective in inhibiting the conversion of t-RAL to t-RA. A 20%
      inhibition was observed at a concentration of only 0.001 mM, and nearly complete
      inhibition was produced at 0.1 mM. Human fetal and embryonic hepatic tissues each
      exhibited significant CYP2E1 expression as assessed with chlorzoxazone 6
      hydroxylation, a highly sensitive western blotting technique, and reverse
      transcriptase-polymerase chain reaction (PCR) (RT-PCR), suggesting that lipid
      peroxidation can be initiated via CYP2E1-catalyzed ethanol oxidation in human
      embryonic hepatic tissues. In summary, these studies suggest that ethanol may
      affect the biosynthesis of t-RA in human prenatal hepatic tissues directly and
      indirectly. Ethanol and its major oxidative metabolite, acetaldehyde, both
      inhibit the generation of t-RA. Concurrently, the CYP2E1-catalyzed oxidation of
      ethanol can initiate lipid peroxidation via generation of a variety of free
      radicals. The lipid peroxides thereby generated could then be further converted
      via CYP2E1-catalyzed reactions to alcohols and aldehydes, including 4-HNE, that
      act as potent inhibitors of t-RA synthesis.

PMID- 10075089
TI  - Sister of P-glycoprotein expression in different tissues.
AB  - Sister of P-glycoprotein (spgp) is a gene that is closely related to the P
      glycoprotein family (Pgps). This class of proteins belongs to the superfamily of
      ATP-binding cassette transporters and is known for its involvement in
      pharmacological drug interactions. Therefore, this study investigated the
      distribution of spgp expression in different tissues known for their high levels
      of Pgps expression such as brain, liver, kidney, small- and large-gut mucosa.
      Analysis was done by using the reverse transcription-polymerase chain reaction.
      In addition to a high expression in the liver, we were able to demonstrate a
      significant spgp expression in brain grey cortex, small- and large-gut mucosa.
      Although Pgps are expressed in the kidney and brain capillary endothelial cells,
      no expression of spgp was detected in these tissues, which might indicate that
      spgp has no function in the blood-brain barrier and is not involved in the renal
      excretion of drugs.

PMID- 10075090
TI  - Stereoselective and substrate-dependent inhibition of hepatic mitochondria beta
      oxidation and oxidative phosphorylation by the non-steroidal anti-inflammatory
      drugs ibuprofen, flurbiprofen, and ketorolac.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) cause a range of adverse effects,
      some of which have been associated with perturbances of lipid metabolic pathways.
      Previous data demonstrating stereoselective formation of the CoA thioester of R
      ibuprofen in particular were suggestive of possible stereoselective effects on
      lipid metabolism. Our aim was to characterise the relative stereoselectivity of
      the effects of ibuprofen, flurbiprofen, and ketorolac (0.01-1.0 mM) on both the
      beta-oxidation of palmitate and oxidative phosphorylation in rat hepatic
      mitochondria as a means of dissecting prostaglandin related from non
      prostaglandin-related events. Beta-oxidation was inhibited stereoselectively by R
      ibuprofen (P = 0.015), non-stereoselectively by R- and S-flurbiprofen (P = 0.002
      and P = 0.004, respectively), and was essentially unaffected by either enantiomer
      of ketorolac. At 0.25 mM, inhibition by R-ibuprofen and both flurbiprofen
      enantiomers was partially reversed by increasing CoA concentrations (0-200
      microM). Mitochondrial respiration was moderately inhibited by both enantiomers
      of ibuprofen and flurbiprofen (P < 0.01), but only by high concentrations (> or =
      1 mM) of the enantiomers of ketorolac (P < 0.01). Uncoupling of oxidative
      phosphorylation measured as stimulation of State 4 respiration contributed to
      these effects. The data support interactions involving both stereoselective CoA
      dependent and non-CoA-dependent mechanisms. The plasma drug concentrations
      required to achieve these effects are not likely to be attained in the majority
      of patients, although these concentrations are achievable in the gastrointestinal
      tract and may contribute to the well-known spectrum of adverse effects in this
      organ. Some patients do experience systemic adverse events which may be mediated
      by these mechanisms.

PMID- 10075091
TI  - Recovery after acute brain injury: function in hospital; dysfunction at home.

PMID- 10075092
TI  - Relation between proton magnetic resonance spectroscopy within 18 hours of birth
      asphyxia and neurodevelopment at 1 year of age.
AB  - The aim of the study was to test the hypotheses that elevated cerebral lactate,
      detected by proton spectroscopy performed within 18 hours of suspected birth
      asphyxia, is associated with adverse outcome, and that increased lactate can be
      used to predict adverse outcome. Thirty-one term infants suspected of having had
      birth asphyxia and seven control infants underwent proton magnetic resonance
      spectroscopy, using three-dimensional chemical shift imaging, within 18 hours of
      birth. Adverse outcome was defined as death or neurodevelopmental impairment at 1
      year of age or more. Nine infants had an adverse outcome. The other 22 and all of
      the control infants remained normal. Median (range) lactate/creatine plus
      phosphocreatine (lactate/creatine) ratios in the abnormal, the normal, and the
      control group were 1.14 (0.17 to 3.81), 0.33 (0 to 1.51), and 0.05 (0 to 0.6)
      respectively (P=0.003). Lactate/creatine >1.0 predicted neurodevelopmental
      impairment at 1 year of age with sensitivity of 66% and specificity of 95%,
      positive and negative predictive values of 86% and 88%, and a likelihood ratio of
      13.2. Elevated cerebral lactate/creatine within 18 hours of birth asphyxia
      predicts adverse outcome.

PMID- 10075093
TI  - Development of lateralized behaviour in the human fetus from 12 to 27 weeks'
      gestation.
AB  - Handedness is the most prominent manifestation of behavioural lateralization in
      the human population. However, little is known about its ontogeny. This study
      examined the prenatal development of behavioural lateralization by observing,
      longitudinally, the occurrence of left- and right-arm movements in 17 human
      fetuses at 3-week intervals from 12 to 27 weeks gestational age. Fetuses
      exhibited significantly more right-arm movements than left-arm movements at every
      gestational age. Throughout all periods of observation, 83.3% of fetuses showed
      more right-arm than left-arm movements. The number of arm movements observed
      peaked at 15 to 18 weeks' gestation and declined rapidly in mid-gestation. The
      occurrence of laterality in early gestation indicates that asymmetric behaviour
      is probably under muscular or spinal, rather than cortical, control and points to
      a 'genetic' origin for such behaviour. The presence of lateralized motor
      behaviour in early gestation suggests it may have a potential causative role for
      subsequent lateralized behaviour and asymmetric brain development.

PMID- 10075094
TI  - Evaluation of the effect of thyroxine supplementation on behavioural outcome in
      very preterm infants.
AB  - Two-hundred infants of <30 weeks gestational age were included in a randomized
      double-blind controlled trial to study the effect of thyroxine administration on
      neurodevelopmental outcome in very preterm children. The infants were given
      either a fixed dose of thyroxine (8 microg/kg birthweight/day) or placebo for the
      first 6 weeks of life. This paper evaluates the effect of thyroxine
      administration on behavioural outcome at the age of 2 years. More externalizing,
      especially destructive, behaviours were found in the group given thyroxine than
      in the placebo group. This difference was more pronounced in boys and in children
      born after 27 weeks' gestation. The thyroxine-treated children with behavioural
      problems had lower plasma-free thyroxine levels than the thyroxine-treated
      children without behavioural problems. This finding suggests that the presence of
      more behavioural problems in the group given thyroxine was not an immediate
      consequence of the treatment.

PMID- 10075095
TI  - Cognitive status, language attainment, and prereading skills of 6-year-old very
      preterm children and their peers: the Bavarian Longitudinal Study.
AB  - The prevalence of intellectual-, language-, and prereading-skill deficits was
      investigated in a geographically defined whole-population sample of very preterm
      children at 6 years of age in southern Germany. The sample consisted of the
      following: 264 very preterm children (75.6% of German-speaking survivors); 264
      term controls (matched for sex, socioeconomic status [SES], marital status and
      age of mother); and a representative normative sample for Bavaria (N=311).
      Compared with term peers, very preterm children scored significantly lower
      (approximately -1SD) on the measures of cognitive and language skills and had
      major cognitive deficits (<-2 SD) 10 to 35 times more often than the controls.
      Deficits in speech articulation and prereading skills (<l0th centile) were three
      to five times more frequent in very preterm children. More than 18% of very
      preterm children had cognitive deficits in more than five areas of functioning,
      compared with no control children. The differences between very preterm children
      and controls remained highly significant when only very preterm children (N= 229)
      and controls (N= 261) without major neurosensory impairment were considered.
      Little evidence for specific cognitive deficits was found once mental processing
      measured in the Kaufman Assessment Battery for Children (K-ABC) was controlled
      for. The effect of preterm birth on cognitive abilities was found to be larger
      than the influence of SES. In conclusion, there was a high prevalence of long
      term multiple cognitive problems in very preterm children. These persistent
      cognitive problems appear to be of pre- or neonatal (treatment) rather than
      postnatal social origin.

PMID- 10075096
TI  - Epilepsy in disintegrative psychosis and infantile autism: a long-term validation
      study.
AB  - This study aimed to investigate the validity of disintegrative psychosis (DP) as
      defined in the ICD-9. The history of epilepsy in 13 subjects with DP was compared
      with that of 39 subjects with infantile autism (IA) who were matched for sex,
      age, IQ, and socioeconomic status (SES). The average follow-up time was 22 and 23
      years (range 11 to 33 years). A significant difference was found between the DP
      and IA groups in terms of incidence of epilepsy, 77% versus 33% respectively. The
      peak period of onset of epilepsy occurred before puberty in both groups.
      Different types of epilepsy were seen, but the psychomotor variant accounted for
      50% in the DP group, while 46% of the IA group had the psychomotor and 62% had
      the grand mal variant. The types are not mutually exclusive. Individuals without
      epilepsy had significantly higher IQ scores than those with epilepsy, but only
      within the IA group. The increased risk of developing epilepsy in the DP group is
      most likely a reflection of an underlying early brain pathology probably present
      in most individuals with DP. On the whole our findings can be seen as a
      contribution to the validation of DP as separate from IA, as these two conditions
      could be distinguished in terms of the way they develop with reference to
      epilepsy.

PMID- 10075097
TI  - Oral-motor dysfunction in children who fail to thrive: organic or non-organic?
AB  - Forty-seven children with non-organic failure to thrive (NOFT) were identified
      from a whole-population survey of children's growth and development. A
      significant proportion (N=17) of these 47 children were found to have oral-motor
      dysfunction (OMD) identified using a previously validated assessment tool. NOFT
      children with OMD and those with normal oral-motor function (N=30) were compared
      in order to ascertain whether there were any neurodevelopmental differences which
      might explain this finding. We hypothesized that children with OMD might have a
      subtle neurodevelopmental disorder. Few psychosocial variables discriminated the
      two groups. However, cognitive stimulation within the home and cognitive-growth
      fostering during mealtimes was much poorer for children with OMD. Some evidence
      has suggested that NOFT children with OMD may be 'biologically' more vulnerable
      from birth. We suggest that the continued use of the term 'non-organic' to
      describe failure to thrive in such children is questionable and requires
      redefining.

PMID- 10075098
TI  - Use of melatonin to treat sleep disorders in tuberous sclerosis.
AB  - The results of a therapeutic trial of the use of melatonin in patients with
      tuberous sclerosis complex who also have severe sleep problems are reported. We
      used a randomized double-blind placebo-controlled crossover design. Seven
      patients with confirmed diagnoses of tuberous sclerosis and significant sleep
      disorder were recruited. We employed three outcome measures: total sleep time,
      time to sleep onset, and number of awakenings. Patients treated with melatonin
      had a small but clinically significant improvement in total sleep time (mean
      improvement 0.55 hours, P<0.05). They also tended to have an improvement in sleep
      onset time but this did not reach statistical significance. Melatonin, in this
      trial, had no discernible effect on sleep fragmentation. We conclude that
      melatonin does have a beneficial effect in prolonging the total sleep time of
      patients with tuberous sclerosis and sleep disorder and that further trials are
      necessary to investigate the issues of optimal dosage, tolerance, and possible
      interactions with other medications.

PMID- 10075099
TI  - Partial lipodystrophy presenting with myopathy.
AB  - A girl with partial lipodystrophy is described presenting with muscle weakness
      and developmental delay several years before lipoatrophy became apparent. The
      patient subsequently developed epilepsy, fatty liver, secondary amenorrhoea,
      hirsutism, insulin-resistant diabetes mellitus, hyperlipidaemia, and
      hypothyroidism. She remains weak with poor exercise tolerance. This case
      illustrates an atypical presentation of the Barraquer-Simon syndrome.

PMID- 10075100
TI  - Fatal haemorrhagic infarct in an infant with homocystinuria.
AB  - Thrombotic and thromboembolic complications are the main causes of morbidity and
      mortality in patients with homocystinuria. However, it is unusual for thrombosis
      and infarction to be the presenting feature leading to investigation for
      homocystinuria and cerebrovascular lesions in the first year of life. We describe
      a previously healthy 6-month-old infant who presented with a large middle
      cerebral-artery territory infarction and died of massive brain swelling.
      Homocystinuria due to cystathionine beta-synthase (CBS) deficiency was diagnosed
      by metabolite analysis and confirmed by enzymatic activity measurement in a
      postmortem liver biopsy. Homocystinuria should be considered in the differential
      diagnosis of venous or arterial thrombosis, regardless of age, even in the
      absence of other common features of the disease. We recommend systematic
      metabolic screening for hyperhomocysteinemia in any child presenting with
      vascular lesions or premature thromboembolism.

PMID- 10075101
TI  - Characteristics of cranial ultrasound white-matter echolucencies that predict
      disability: a review.

PMID- 10075102
TI  - 'Erythrocyte glutathione system and children with Down syndrome'.

PMID- 10075103
TI  - 'Sleep EEG and developmental dysphasia'.

PMID- 10075104
TI  - Differential signalling by variant ligands of the T cell receptor and the kinetic
      model of T cell activation.
AB  - The structural basis of T cell activation through the T cell receptor is still a
      major unresolved issue in T cell biology. The wealth of information on the
      generation and structure of T cell receptor ligands and the biochemistry of
      signal transduction from this receptor have been useful in the initial approach
      to explain how T cell activation occurs. More recently, the generation of variant
      T cell receptor ligands with partial agonist or antagonist properties, the
      determination of crystal structures for unengaged and engaged T cell receptors,
      and the kinetics of T cell receptor interactions with peptide:MHC molecule
      complexes have provided new insights on T cell receptor function. The common
      theme arising from these experiments is that the T cell receptor is a versatile
      signalling machine, with an inherent flexibility for ligand recognition that
      translates in different signalling patterns. Here, I will review the data on
      differential signalling from the T cell receptor upon recognition of partial
      agonist and antagonist ligands and how these data impact on a more general
      kinetic model of T cell receptor-mediated activation.

PMID- 10075105
TI  - Neurotransmitter-mediated open-field behavioral action of CGRP.
AB  - The effects of central administration of calcitonin gene-related peptide (CGRP)
      on open-field activity were examined in male rats. Three doses (250 ng, 500 ng
      and 1 microg) of CGRP given intracerebroventricularly (i.c.v.) were tested on the
      ambulatory, rearing and grooming activities of the animals. One microg of peptide
      significantly decreased the ambulatory activity and increased the rearing and
      grooming activities 30 min after the treatment. The animals were pretreated with
      different receptor antagonists in doses which by itself did not affect the
      behavioural paradigm. The decrease in ambulation induced by CGRP was antagonized
      by acetylcholine-, opioid-, 5HT-receptor and beta-adrenoceptor antagonists. CGRP
      induced increase in rearing activity was blocked by naloxone, phenoxybenzamine
      and propranolol. The CGRP-induced increase in grooming behavior was prevented by
      atropine, haloperidol, naloxone, methysergide and propranolol. The results
      suggest that different neurotransmitter systems are involved in the action of
      CGRP on open-field behavior in rats.

PMID- 10075106
TI  - Diabetes abolishes the vascular protective effects of estrogen in female rats.
AB  - Estrogen is known to exert a protective effect against cardiovascular disease.
      However, women with diabetes have three times the risk as compared with age
      matched non-diabetic women. Our previous study on aortic rings of ovariectomized
      (OVX) female rats treated with 17-beta-estradiol (E2) demonstrated that the
      beneficial effect of estrogen is related to the basal release of NO from
      endothelial cells. In the present study, in order to understand why estrogen
      protection is abolished in diabetes, we tested vascular responses in OVX,
      streptozotocin-diabetic female rats and their non-diabetic controls receiving or
      not E2 replacement. Concentration-response curves to norepinephrine (NE) showed
      attenuation of the contractile response in E2-treated diabetic, with respect to
      non-diabetic preparations. This response was further impaired in diabetic, E2
      deprived rats. The basal release of NO, as evaluated by concentration-related
      responses to N(G)-methyl-L-arginine acetate in NE-precontracted aortic rings, was
      found to be impaired in E2-treated diabetic rats, no further effect being induced
      by E2 deprivation. The endothelium-dependent relaxation produced by carbachol did
      not change between groups, whereas the relaxation produced by histamine was
      enhanced by both diabetes and E2 deprivation. However, E2 treatment counteracted
      the response to histamine only in preparations from non-diabetic animals.
      Finally, the relaxation induced by sodium nitroprusside, an endothelium
      independent relaxant agent, was comparable between groups. These findings suggest
      that the lack of protective effects of estrogen in diabetes may be mainly
      ascribed to the failure of estrogen to reverse the impaired basal release of NO
      and the abnormal relaxation to histamine, which are observed in the aorta of
      diabetic rats.

PMID- 10075107
TI  - Opposite effects of D-glucose pentaacetate and D-galactose pentaacetate anomers
      on insulin release evoked by succinic acid dimethyl ester in rat pancreatic
      islets.
AB  - Both alpha- and beta-D-glucose pentaacetate (1.7 mM each) augmented, to almost
      the same extent, insulin release caused by succinic acid dimethyl ester (10.0 mM)
      in rat pancreatic islets. The secretory response to these hexose esters largely
      exceeded that evoked by unesterified D-glucose tested at the same concentration
      (1.7 mM). The release of insulin provoked by succinic acid dimethyl ester was
      inhibited, however, by alpha-D-galactose pentaacetate, whilst being unaffected by
      beta-D-galactose pentaacetate (each also 1.7 mM). It appears, therefore, that the
      insulinotropic action of hexose esters is not attributable solely to the
      catabolism of their carbohydrate moiety, but may also involve a receptor system
      that displays anomeric specificity and can be directly activated or inhibited by
      the esters themselves. Hence, it is proposed that selected esters of non-nutrient
      monosaccharides may represent new tools to either stimulate insulin release in
      diabetes or prevent excessive hormonal secretion in situations of
      hyperinsulinemia.

PMID- 10075108
TI  - Thermal preconditioning protects rat cardiac muscle cells from doxorubicin
      induced apoptosis.
AB  - Doxorubicin (DOX=adriamycine), an effective chemotherapeutic agents for cancers,
      has severe cardiotoxicity. In the paresent study, we examined the protective
      effect of thermal preconditioning (TP) against apoptosis of rat cardiac muscle
      cells induced by DOX. Treatment with DOX (10 microM) for 24 hrs resulted in
      apoptosis of cardiac muscle cells, which was evaluated by examining "DNA ladder"
      formation and TUNEL staining. The number of TUNEL-positive cells was
      significantly decreased in cells subjected to TP by incubation at 42 degrees C
      for 30 min, 24 hrs prior to DOX-treatment. Antisense oligonucleotides of the heat
      shock protein (HSP) 70 blunted this effect. These results indicate that DOX
      induced apoptosis in cardiac muscle cells is prevented by TP, at least in part,
      via a HSP70-mediated mechanism.

PMID- 10075109
TI  - Evidence for a multidrug resistance-associated protein 1 (MRP1)-related transport
      system in cultured rat liver biliary epithelial cells.
AB  - Cellular accumulation and efflux of the anionic fluorescent dye carboxy-2',7'
      dichlorofluorescein (CF) were studied in rat liver SDVI cells thought to derive
      from primitive bile ductules, in order to characterize carrier-related membrane
      transport of organic anions in epithelial cells. Probenecid, a common blocker of
      anion transport, was found to strongly enhance CF levels in SDVI cells in a dose
      dependent manner through inhibition of dye efflux. Such an outwardly-directed
      transport was demonstrated to be temperature-dependent and down-regulated by
      various metabolic inhibitors, therefore outlining its requirement for energy; it
      was shown to be Na+- and membrane potential-independent and inhibited by anionic
      drugs such as indomethacin, indoprofen and rifamycin B. These functional features
      are closed to those described for multidrug resistance-associated protein 1
      (MRP1) that was furthermore demonstrated, in contrast to P-glycoprotein, to be
      expressed in SDVI cells and to lower CF accumulation in MRP1-overexpressing drug
      resistant tumor cells. These data therefore suggest that active membrane
      transport of organic anions such as CF occurs in epithelial cells like cultured
      liver biliary SDVI cells through a MRP1-related efflux system.

PMID- 10075110
TI  - Regional brain metabolic activation during craving elicited by recall of previous
      drug experiences.
AB  - Cocaine cues elicit craving and physiological responses. The cerebral circuits
      involved in these are poorly understood. The purpose of this study was to assess
      the relation between regional brain activation and cocaine cue elicited
      responses. Thirteen right-handed cocaine abusers were scanned with positron
      emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice; during an
      interactive interview about neutral themes and during an interactive interview
      about cocaine themes designed to elicit cocaine craving. In parallel the
      behavioral (rated from 0: felt nothing to 10: felt extreme) and cardiovascular
      responses were recorded. During the cocaine theme interview subjects reported
      higher self reports for cocaine craving (+2.5+/-3.3, p < or = 0.02) and had
      higher heart rates (+4.7+/-7.2%, p < or = 0.001), systolic (+4+/-4%, p < or =
      0.0001), and diastolic blood pressures (+2.6+/-3.8%, p < or = 0.003) than during
      the neutral interview. Absolute and relative metabolic values in the
      orbitofrontal (+16.4+/-17.1%, p < or = 0.005; +11.3+/-14.3%, p < or = 0.008) and
      left insular cortex (+21.6+/-19.6%, p < or = 0.002; +16.7+/-19.7%, p < or = 0.01)
      and relative values in cerebellum (+17.9+/-14.8%, p < or = 0.0008) were higher
      during the cocaine theme than during the neutral theme interview. Relative
      metabolic values in the right insular region (p < or = 0.0008) were significantly
      correlated with self reports of cocaine craving. Activation of the temporal
      insula, a brain region involved with autonomic control, and of the orbitofrontal
      cortex, a brain region involved with expectancy and reinforcing salience of
      stimuli, during the cocaine theme support their involvement with craving in
      cocaine addicted subjects.

PMID- 10075111
TI  - Suppressive effects of CTLA4-Ig on nasal allergic reactions in presensitized
      murine model.
AB  - Ag-specific T cell activation requires the engagement of T cell receptor (TCR)
      with antigen in the context of MHC, and the engagement of appropriate
      costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory
      pathway plays an important role in the induction of T helper (Th) cells in T-cell
      dependent immune reactions. In this study, we evaluated the effects of blocking
      the costimulatory pathway by systemic administration of CTLA4-Ig during repeated
      nasal antigen challenges in systemically presensitized mouse. The antigen-induced
      early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal
      eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of
      serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the
      treatment. In relation to cytokine levels in the tissue extracts of the nasal
      mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels
      of IL-5 and IFN-gamma were not affected by the treatment. These results suggest
      that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2
      related allergic reactions in the nose.

PMID- 10075112
TI  - Cadmium-bound metallothionein induces apoptosis in rat kidneys, but not in
      cultured kidney LLC-PK1 cells.
AB  - The ability of cadmium-bound metallothionein(Cd-MT) to induce apoptosis was
      investigated in vivo and in vitro. Administration of purified Cd-MT (0.15 mg MT
      bound Cd per kg body weight) to the rat induces DNA fragmentation, a biochemical
      characteristic of apoptosis in the kidney at 16 h, which was detectable by
      ethidium bromide staining on an agarose gel. It was still detected 24 h after
      administration. Induction of apoptosis by Cd-MT was specific to kidney; it was
      not observed in cerebrum, cerebellum, heart, lung, liver, testis, dorsolateral
      prostate, and ventral prostate. In contrast, addition of Cd-MT (0.01-100 microM)
      to the cultured porcine kidney LLC-PK1 cells failed to induce apoptosis under the
      condition where cadmium chloride (10 microM) did. There was no additivity of
      induction of apoptosis by CdCl2 (10 microM) in the presence of Cd-MT (0.01-100
      microM). To examine the effect of intracellular MT on cadmium-induced apoptosis
      in cultured cells, new cell lines were established, which constitutively produce
      MT, being termed as Cd(r)-LLC-PK1 cells since Cd-MT exogenously added had much
      less permeability to the cultured cells. Followed by exposure of wild-type LLC
      PK1 cells to 50 microM CdCl2 for 24 h, the surviving cells(Cd(r)-LLC-PK1 cells)
      induce MT at the level of 1.9 microg/2 x 10(6) cells. In Cd(r)-LLC-PK1 cells, 10
      microM CdCl2 failed to induce apoptosis, but 60 microM CdCl2 could exert the
      apoptotic response, indicating that intracellular MT which was induced by CdCl2
      did not facilitate CdCl2-elicited apoptosis. Furthermore, chromatin in rat
      kidneys was condensed by Cd-MT, but not that in LLC-PK1 cells. Thus, Cd-MT
      induces apoptosis in rat kidneys, but not in the cultured renal cells, suggesting
      that the ionic form of cadmium was required for programmed cell death.

PMID- 10075113
TI  - Detection of fluoxetine in brain, blood, liver and hair of rats using gas
      chromatography-mass spectrometry.
AB  - This study reports the measurements of fluoxetine in discrete brain regions,
      blood, liver and hair of male rats injected with 10 mg/kg fluoxetine HCl for 15
      consecutive days. Concentrations of the antidepressant were obtained by gas
      chromatography-mass spectrometry (GC-MS) methodology. In brain, fluoxetine levels
      were unevenly distributed, with the raphe nucleus containing the highest amounts
      relative to the hypothalamus or striatum. Fluoxetine was also measured in blood
      and liver roughly paralleling those ratios described in previous rodent studies.
      Of potential interest, fluoxetine was found to accumulate in rat hair after
      chronic treatment. Detection of fluoxetine in hair by GC-MS could be used as a
      marker for probative analyses.

PMID- 10075114
TI  - A chelating agent possessing cytotoxicity and antimicrobial activity: 7
      morpholinomethyl-8-hydroxyquinoline.
AB  - 7-Morpholinomethyl-8-hydroxyquinoline (MO-8HQ), which like 8-hydroxyquinoline
      (8HQ) readily forms a chelate, was synthesized and found to possess cytotoxicity
      and antimicrobial activity. Both 8HQ and MO-8HQ were cytotoxic to human carcinoma
      cell lines at micromolar concentrations. MO-8HQ also inhibited DNA synthesis of
      tumor cells at micromolar concentrations, suggesting that MO-8HQ might chelate
      metals necessary for the enzymatic catalysis of DNA biosynthesis. MO-8HQ was more
      active against gram positive bacteria than gram negative bacteria and its potency
      correlated with iron chelation. An "unsaturated" chelate with a MO-8HQ to Fe
      ratio of 2:1 exhibited greater antibacterial activity than MO-8HQ alone. Among
      the organisms tested, Micrococcus flavus was most susceptible with a MIC of 3.9
      microg/ml. MO-8HQ also exhibited anti-fungal activity at 7-15 microg/ml. MO
      8HQ:Fe chelate markedly increased the susceptibility of Escherichia coli to
      deoxycholate. Addition of Ca2+ or Mg2+ reversed the sensitivity of bacteria to
      deoxycholate as well as to rifampicin. It is suggested that MO-8HQ exerts its
      biological activity as a membrane-active agent through metal ion chelation.

PMID- 10075115
TI  - Effect of perinatal synthetic steroid hormone (allylestrenol, diethylstilbestrol)
      treatment (hormonal imprinting) on the bone mineralization of the adult male and
      female rat.
AB  - Neonatal treatment with allylestrenol or diethylstilbestrol (DES) reduced the
      bone mineral content (BMC/bw) of the adult (four months old) female rats, without
      influencing bone mineral density (BMD/bw). In males these neonatal treatments
      elevated BMC and BMD alike. Ovariectomy alone decreased BMC and BMD alike;
      however the neonatal hormone treatments did not influence this reduced value.
      Ovariectomy of two months old animals increased body weight without the influence
      of neonatal hormone treatments. In adult males, the body weight was reduced
      significantly by neonatal DES and non-significantly by neonatal allylestrenol
      treatment. The experiments call attention to the possible human bone-effects of
      allylestrenol, which was used in the last decades as medication protecting
      endangered pregnancies.

PMID- 10075116
TI  - Modulation of radioresponse of glyoxalase system by curcumin.
AB  - Human beings have been exposed to radiation for many years. It is quite possible
      that antioxidant phytochemicals consumed in their diet might be providing a
      variable degree of radioprotection. However, their radiomodifying ability is not
      well understood. In the present work, curcumin (diferuloyl methane), a
      phytochemical present in the rhizome of Curcuma longa Linn. has been examined for
      its radioprotective property using the glyoxalase system which is vital for
      various biological functions. Curcumin (5, 25 and 50 mg/kg body weight) in olive
      oil was given orally to Swiss albino male mice (7-8 weeks old) daily for 2 weeks
      and irradiated with different doses of gamma-radiation (0-6 Gy) at 0.027 Gy per
      second dose rate on last day of the treatment. The specific activities of
      glyoxalase I and II were determined in the liver and spleen. The treatment of
      curcumin prior to irradiation restored the specific activity of glyoxalase system
      to almost the control level which was suggestive of the radioprotective ability
      of curcumin. Free radical scavenging and electron/hydrogen donation are probable
      attributes for the protective effect of curcumin.

PMID- 10075117
TI  - Screening of plants used by Southern African traditional healers in the treatment
      of dysmenorrhoea for prostaglandin-synthesis inhibitors and uterine relaxing
      activity.
AB  - Plants used by Southern African traditional healers for the treatment of
      menstrual pains were screened for prostaglandin-synthesis inhibitors and the
      ability to reduce isolated uterine muscle contraction using the cyclooxygenase
      and in vitro uterine bioassays respectively. Prostaglandins are synthesized from
      arachidonic acid and the enzyme that drives this reaction is cyclooxygenase. The
      excessive production of prostaglandins by the myometrium and endometrium induces
      uterine contractions. Inhibition of cyclooxygenase and hence of the prostaglandin
      biosynthetic pathway may lead to relief of menstrual pain. Ten plants used by
      traditional healers for menstrual pains were assayed for cyclooxygenase
      inhibitory activity. Several plant extracts exhibited high inhibitory activity in
      the assay. The highest activities were obtained with ethanolic extracts of
      Siphonochilus aethiopicus, Cenchrus ciliaris and Solanum mauritianum. Generally
      ethanolic extracts gave higher activity than the aqueous extracts. None of the
      ethanolic plant extracts were able to relax or reduce the contractions of the
      precontracted guinea pig uterus.

PMID- 10075118
TI  - A search for anti-viral properties in Panamanian medicinal plants. The effects on
      HIV and its essential enzymes.
AB  - Aqueous and methanolic extracts of 39 Panamanian medicinal plants were tested for
      anti-human immunodeficiency virus (HIV) effects. The extracts were tested for the
      inhibition of HIV-induced cytopathic effects in cultured cells, HIV-reverse
      transcriptase (RT) and HIV-protease (PR) enzymes. The water extract of the
      branches of Jatropha curcas (Euphorbiaceae) inhibited strongly the HIV-induced
      cytopathic effects with low cytotoxicity. On the other hand, the water extracts
      of the whole plant of Chamaesyce hyssopifolia (Euphorbiaceae), the leaves of
      Cordia spinescens (Boraginaceae) and the aerial parts of Hyptis lantanifolia
      (Labiatae), and the methanol extract of the aerial parts of Tetrapteris
      macrocarpa (Malpighiaceae) were potent inhibitors of HIV-RT (IC50: 6-8
      microg/ml). Seven out of 39 plants were found to be moderate inhibitors of HIV-PR
      (IC50: 43-100 microg/ml). Furthermore, we report on the respective inhibitory
      substances of J. curcas, C. hyssopifolia and C. spinescens, and their possible
      mechanism of action.

PMID- 10075119
TI  - Uncaria tomentosa (Willd.) DC.--ethnomedicinal use and new pharmacological,
      toxicological and botanical results.
AB  - The medicinal system of the Ashaninka Indians in Peru is portrayed. Three
      categories of medical disorders and healers are recognized. A human is viewed to
      consist of a physical and a spiritual being who communicate with each other by
      means of a regulating element. The significance of Uncaria tomentosa (Willd.) DC.
      (Rubiaceae), locally known as una de gato, in traditional medicine is emphasized
      by its exclusive use by priests to influence this regulation. Pharmacological and
      toxicological results obtained with extracts or isolated compounds are
      summarized. Pentacyclic oxindole alkaloids stimulate endothelial cells in vitro
      to produce a lymphocyte-proliferation-regulating factor. Tetracyclic oxindole
      alkaloids act as antagonists. A significant normalization of lymphocyte
      percentage was observed in vivo although total leucocyte numbers did not change.

PMID- 10075120
TI  - Pharmacology of Casimiroa edulis IV. Hypotensive effects of compounds isolated
      from methanolic extracts in rats and guinea pigs.
AB  - Bioassay-directed fractionation of the methanolic extract of seeds of Casimiroa
      edulis led to the isolation of seven constituents with cardiovascular activity,
      namely the new compound synephrine acetonide and the known compounds N
      monomethylhistamine, N,N-dimethylhistamine, proline, N-methylproline, gamma
      aminobutyric acid and casimiroedine. In anesthetized rats, both histamine
      derivatives produced transient hypotension mediated via H1-histaminergic
      receptors and in the case of N,N-dimethylhistamine, via nitric oxide release.
      Synephrine acetonide produced transient hypertension and tachycardia, mediated
      via alpha- and alpha- and beta-adrenergic receptores, respectively. The
      chromatographic zone containing N-methyproline, proline and gamma-aminobutyric
      acid elicited marked and prolonged hypotension. Finally, casimiroedine did not
      modify the blood pressure of anesthetized rats, but lowered it persistently in
      anesthetized guinea pigs. It was concluded that hypotension produced by C. edulis
      is due to several active components. The immediate effect can be attributed to
      the histamine derivatives acting on H1-receptors. More prolonged hypotension
      would be produced by the mixture of amino acids through an unknown mechanism, as
      well as by casimiroedine, possibly by activation of H3-receptors. Hypotension is
      partially offset by synephrine acetonide through adrenergic mechanisms.

PMID- 10075121
TI  - Effect of Korean folk medicine 'Chung-Dae-San' on mast cell-dependent
      anaphylactic reaction.
AB  - We investigated the effect of the herbal formulation 'Chung-Dae-San' (CDS) on
      anaphylactic reactions. CDS inhibited compound 48/80-induced anaphylactic shock
      100% with the dose of 10(0) g/kg body weight (BW). When CDS was given as
      pretreatment at concentrations ranging from 10(-4) to 10(0) g/kg BW, the serum
      histamine levels induced by compound 48/80 were reduced in a dose-dependent
      manner. We also investigated the effect of CDS on mast cell-dependent passive
      cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE antibody.
      CDS potently inhibited PCA when administered orally, topically, intraperitoneally
      or intradermally. However, it did not show inhibitory activity when administered
      intravenously. CDS dose-dependently inhibited the histamine release from the rat
      peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, the
      level of cAMP in RPMC, when CDS was added, significantly increased about 4-fold
      at 4 min compared with that of basal cells. These results indicate that CDS may
      possess strong antianaphylactic activity and also suggest the differential
      activity following administration routes may be caused by difference in
      bioavailability.

PMID- 10075122
TI  - Hypolipidaemic action of Tinospora cordifolia roots in alloxan diabetic rats.
AB  - We undertook the present study to evaluate the hypolipidaemic effect of an
      aqueous extract of Tinospora cordifolia roots, an indigenous plant used in
      Ayurvedic medicine in India. Administration of the extract of T. cordifolia roots
      (2.5 and 5.0 g/kg body weight) for 6 weeks resulted in a significant reduction in
      serum and tissue cholesterol, phospholipids and free fatty acids in alloxan
      diabetic rats. The root extract at a dose of 5.0 g/kg body weight showed highest
      hypolipidaemic effect. The effect of T. cordifolia roots at 2.5 and 5.0 g/kg body
      weight was better than glibenclamide. Insulin restored all the parameters to near
      normal values.

PMID- 10075123
TI  - Antiherpes virus activity of extracts from the medicinal plant Geranium
      sanguineum L.
AB  - The herpes virus inhibitory effect of five extracts from the Bulgarian medicinal
      plant Geranium sanguineum L. (Geraniaceae) was investigated. The water extract
      (WE) from the aerial roots of the plant was the least toxic for cell cultures and
      inhibited significantly the replication of herpes simplex virus type 1 and type 2
      (EC50 = 3.6-6.2 microg/ml) as shown by the reduction of virus induced
      cytopathogenic effect (CPE) and the protection of cells in MTT assay. The
      inhibition was dose-related, strain-specific and depended on virus inoculum. In
      higher concentrations (MIC90 = 120 microg/ml) the preparation exhibited strong
      extracellular virus inactivating activity. The presence of WE throughout the
      whole replicative cycle was necessary for the full expression of the antiviral
      effect. In a preliminary experiment in albino guinea pigs the extract delayed the
      development of herpetic vesicles following primary infection with HSV-1, strain
      Kupka. Phytochemical investigation of the plant preparation revealed the presence
      of flavonoids, catechins, a polyphenolic acid and condensed tannins. The
      inhibitory effect of the extract on herpes simplex virus replication is related
      to the rich content of polyphenol compounds.

PMID- 10075124
TI  - Wide spectrum antibacterial and antifungal activities in the seeds of some
      coprophilous plants of north Indian plains.
AB  - In a survey at Lucknow, India, the seedlings of plant species which are
      prescribed in the Indian traditional system of medicine for a variety of
      infectious diseases were found to predominate on fresh or decomposing cattle
      dung, a harsh medium for plant growth due to high microbial load and other
      abiotic factors. Plants of most of the common species did not occur on the cattle
      dung heaps. It was hypothesized that plant species which are able to grow on
      cattle dung may have antimicrobial compounds in their seeds to protect them from
      microbial attack. In confirmation, the seeds of 15 of the coprophilous (kopros-
      dung, philein--to love) plant species, identified as occurring most frequently on
      fresh/decomposing cattle dung were directly tested against eight bacterial and
      three fungal strains. Interestingly, seeds of all the examined species exhibited
      antimicrobial activity. The seeds of the species found more frequently on the
      cattle dung heaps possessed higher levels of antimicrobial activities.

PMID- 10075125
TI  - Antiviral activity in Argentine medicinal plants.
AB  - In an ethnopharmacological screening of selected medicinal plants used in
      Argentina for the treatment of infectious diseases, aqueous extracts of five
      species were assayed in vitro to detect antiviral activity against herpes simplex
      virus type 1 (HSV-1), respiratory syncytial virus (RSV) and adenovirus serotype 7
      (ADV-7). Polygonum punctatum, Lithraea molleoides, Sebastiania brasiliensis and
      Sebastiania klotzschiana but not Myrcianthes cisplatensis showed in vitro
      antiherpetic activity with 50% effective dose (ED50) ranging from 39 to 169
      microg/ml. P. punctatum, L. molleoides and M. cisplatensis showed antiviral
      activity against RSV with ED50 ranging from 78 to 120 microg/ml. None of the
      extracts had antiviral activity against ADV-7. The differences between their
      maximal non cytotoxic concentration and their antiviral activity values were high
      enough to justify further analysis.

PMID- 10075126
TI  - Anti-inflammatory effects of Taiwan folk medicine 'Teng-Khia-U' on carrageenan-
      and adjuvant-induced paw edema in rats.
AB  - 'Teng-Khia-U' is a folk medicine from Taiwan, derived from the entire plants of
      Elephantopus scaber L., E. mollis H.B.K. and Pseudoelephantopus spicatus (Juss.)
      Rohr (Compositae). To evaluate the anti-inflammatory activities of these crude
      drugs, models with carrageenan-induced acute arthritis and complete Freund's
      adjuvant (CFA)-induced chronic arthritis in rats were conducted. The results
      indicated that pretreatment with 'Teng-Khia-U' significantly inhibited the
      carrageenan-induced acute arthritis. Moreover, they also significantly suppressed
      the development of chronic arthritis induced by CFA.

PMID- 10075127
TI  - Antistressor effect of Withania somnifera.
AB  - Withania somnifera is an Indian medicinal plant used widely in the treatment of
      many clinical conditions in India. Its antistressor properties have been
      investigated in this study using adult Wistar strain albino rats and cold water
      swimming stress test. The results indicate that the drug treated animals show
      better stress tolerance.

PMID- 10075128
TI  - Discourse structures in medical reports--watch out! The generation of
      referentially coherent and valid text knowledge bases in the MEDSYNDIKATE system.
AB  - The automatic analysis of medical narratives currently suffers from neglecting
      text structure phenomena such as referential relations between discourse units.
      This has unwarranted effects on the descriptional adequacy of medical knowledge
      bases automatically generated from texts. The resulting representation bias can
      be characterized in terms of incomplete, artificially fragmented and
      referentially invalid knowledge structures. We focus here on four basic types of
      textual reference relations, viz. pronominal and nominal anaphora, textual
      ellipsis and metonymy and show how to deal with them in an adequate text parsing
      device. Since the types of reference relations we discuss show an increasing
      dependence on conceptual background knowledge, we stress the need for formally
      grounded, expressive conceptual representation systems for medical knowledge. Our
      suggestions are based on experience with MEDSYNDIKATE, a medical text knowledge
      acquisition system designed to properly deal with various sorts of discourse
      structure phenomena.

PMID- 10075129
TI  - Development of a cross-thesaurus with Internet-based refinement supported by
      UMLS.
AB  - Combinatorial terminological systems are appearing, to solve the issues related
      to flexibility and precision of representation requested by modern healthcare
      information systems and in particular by messaging standards. The development of
      a robust system of descriptors ('cross-thesaurus') is a crucial activity in the
      production of combinatorial terminological systems. We developed a tool (I
      BROWSE) to produce a cross-thesaurus by analysing existing terminological
      corpora. To facilitate the work of experts and to produce re-usable results, our
      application interacts via the Internet with the UMLS Knowledge Sources Server. We
      applied our tool on 6372 dissections on surgical procedures produced in the
      project GALEN-IN-USE, as a part of the internal Quality Assurance Program.
      Support from UMLS seems mostly promising about descriptors on <anatomy>,
      <pathological structure>, <pathological process> and <physiological process>.
      Additional assistance can be given to domain experts on less frequent descriptors
      on pervasive modifiers. We plan to apply our tool also to production of
      terminological standards in CEN, as a part of a world-wide process of gradual
      convergence and transformation of coding systems into second-generation systems
      and terminological services.

PMID- 10075130
TI  - Nonlinear analysis of the performance and reliability of wavelet singularity
      detection based denoising for Doppler ultrasound fetal heart rate signals.
AB  - Many studies on the physiology of the cardiovascular system revealed that
      nonlinear chaotic dynamics govern the generation of the heart rate signal. This
      is also valid for the fetal heart rate (FHR) variability, where however the
      variability is affected by many more factors and is significantly more
      complicated than for the adult case. Recently an adaptive wavelet denoising
      method for the Doppler ultrasound FHR recordings has been introduced. In this
      paper the performance and reliability of that method is confirmed by the
      observation that for the wavelet denoised FHR signal, a deterministic nonlinear
      structure, which was concealed by the noise, becomes apparent. It provides strong
      evidence that the denoising process removes actual noise components and can
      therefore be utilized for the improvement of the signal quality. Hence by
      observing after denoising a significant improvement of the 'chaoticity' of the
      FHR signal we obtain strong evidence for the reliability and efficiency of the
      wavelet based denoising method. The estimation of the chaoticity of the FHR
      signal before and after the denoising is approached with three nonlinear analysis
      methods. First, the rescaled scale analysis (RSA) technique reveals that the
      denoising process increases the Hurst exponent parameter as happens when additive
      noise is removed from a chaotic signal. Second, the nonlinear prediction error
      evaluated with radial basis function (RBF) prediction networks is significantly
      lower at the denoised signal. The significant gain in predictability can be
      attributed to the drastic reduction of the additive noise from the signal by the
      denoising algorithm. Moreover, the evaluation of the correlation coefficient
      between actual and neural network predicted values as a function of the
      prediction time displays characteristics of chaos only for the denoised signal.
      Third, a chaotic attractor, reconstructed with the embedding dimension technique,
      becomes evident for the denoised signal, while it is completely obscured for the
      original signals. The correlation dimension of the reconstructed attractor for
      the denoised signal tends to reach a value independent of the embedding
      dimension, a sign of deterministic chaotic signal. In contrast for the original
      signal the correlation dimension increases steadily with the embedding dimension,
      a fact that indicates strong contribution of noise.

PMID- 10075131
TI  - Protocol-based reasoning in diabetic patient management.
AB  - We propose a system for teleconsultation in Insulin Dependent Diabetes Mellitus
      (IDDM) management, accessible through the use of the net. The system is able to
      collect monitoring data, to analyze them through a set of tools, and to suggest a
      therapy adjustment in order to tackle the identified metabolic problems and to
      fit the patient's needs. The therapy revision has been implemented through the
      Episodic Skeletal Planning Methodi, it generates an advice and employs it to
      modify the current therapeutic protocol, presenting to the physician a set of
      feasible solutions, among which she can choose the new one.

PMID- 10075132
TI  - Web-based training: a new paradigm in computer-assisted instruction in medicine.
AB  - Computer-assisted instruction (CAI) programs based on internet technologies,
      especially on the world wide web (WWW), provide new opportunities in medical
      education. The aim of this paper is to examine different aspects of such
      programs, which we call 'web-based training (WBT) programs', and to differentiate
      them from conventional CAI programs. First, we will distinguish five different
      interaction types: presentation; browsing; tutorial dialogue; drill and practice;
      and simulation. In contrast to conventional CAI, there are four architectural
      types of WBT programs: client-based; remote data and knowledge; distributed
      teaching; and server-based. We will discuss the implications of the different
      architectures for developing WBT software. WBT programs have to meet other
      requirements than conventional CAI programs. The most important tools and
      programming languages for developing WBT programs will be listed and assigned to
      the architecture types. For the future, we expect a trend from conventional CAI
      towards WBT programs.

PMID- 10075133
TI  - Who is afraid of the system? Doctors' attitude towards diagnostic systems.
AB  - Although physicians indicate a need for diagnostic support, devices that may
      provide such support, i.e. computer-aided systems are not in widespread use.
      Practising physicians often blame this on the computer. We have tested this idea
      by asking physicians to solve a number of patient problems with the help of a
      diagnostic decision support system in a realistic environment. As we expected,
      the use of the computer was not found to be an obstacle. However, the support
      part of the system, which was meant to stimulate the user's thoughts and to
      prompt him to review his conclusions, turned out to be problematic. The
      critiquing function of the system hardly seemed appreciated by the participants,
      and only rarely influenced their diagnostic judgement. Sources of additional
      information were ignored. We have come to the conclusion that the combination of
      physicians and computer-aided diagnosis deserves further and thorough
      exploration.

PMID- 10075134
TI  - ATP dependent K+ channel: a novel therapeutic target in unstable angina.

PMID- 10075135
TI  - The place for beta-blockers in treating hypertension.

PMID- 10075136
TI  - Hotline sessions at the 20th European Congress of Cardiology.

PMID- 10075137
TI  - Treatment with beta-blockers for the primary prevention of the cardiovascular
      complications of hypertension.

PMID- 10075138
TI  - Diuretics, beta-blockers, and gin and tonic.

PMID- 10075139
TI  - The transmyocardial laser revascularization international registry report.
AB  - AIMS: This report aimed to provide an analysis of the data submitted from Europe
      and Asia on transmyocardial laser revascularization. METHODS AND RESULTS:
      Prospective data was recorded on 967 patients with intractable angina not
      amenable to conventional revascularization in 21 European and Asian centres
      performing transmyocardial laser revascularization using the PLC Medical Systems
      CO2 laser. Patient characteristics, operative details and early complications
      following transmyocardial laser revascularization were recorded. The in-hospital
      death rate was 9.7% (95% confidence interval 7.8% to 11.6%). Other early
      complications were consistent with similar cardiothoracic surgical procedures.
      There was a decrease of two or more Canadian Cardiovascular Score angina classes
      in 47.3%, 45.4% and 34.0% of survivors at 3, 6 and 12 months follow-up,
      respectively (P=0.001 for each). Treadmill exercise time increased by 42 s at 3
      months (P=0.008), 1 min 43 s at 6 months (P<0.001) and 1 min 50 s at 12 months
      (P<0.001) against pre-operative times of 6 min. CONCLUSION: Uncontrolled registry
      data suggest that transmyocardial laser revascularization may lead to a decrease
      in angina and improved exercise tolerance. It does, however, have a risk of peri
      operative morbidity and mortality. Definitive results from randomized controlled
      trials are awaited.

PMID- 10075140
TI  - Heart rate variability and ischaemia in patients with coronary heart disease and
      stable angina pectoris; influence of drug therapy and prognostic value. TIBBS
      Investigators Group. Total Ischemic Burden Bisoprolol Study.
AB  - AIMS: Determination of the influence of therapy with bisoprolol and nifedipine on
      the heart rate variability of patients from the Total Ischemic Burden Bisoprolol
      Study and examination of the prognostic value. METHODS AND RESULTS: Four hundred
      and twenty-two patients with stable angina were included. The heart rate
      variability was determined over a period of 24 h. Parameters determined: standard
      deviation of the mean of all corrected RR intervals, standard deviation of all 5
      min mean cycle lengths, square root of the mean of the squared differences of
      successive corrected RR intervals. Nifedipine reduced the mean values of all
      heart rate variability parameters tested. Square root of the mean of the square
      differences of successive corrected RR intervals increased under bisoprolol.
      Standard deviation of the mean of all corrected RR intervals and standard
      deviation of all 5 min mean cycle lengths increased from low baseline values and
      declined from higher baseline values. The increase in heart rate variability
      under therapy was accompanied by a tendency towards a better prognosis. Patients
      with an increase in heart rate variability and simultaneous complete suppression
      of ischaemia under therapy displayed no serious events in the course of one year.
      CONCLUSIONS: The increase in the heart rate variability, which can be regarded as
      prognostically favourable, was predominantly observed under bisoprolol. The
      parameter constellation of an increase in heart rate variability and complete
      ischaemia suppression on the 48-h Holter ECG was associated with the greatest
      benefit.

PMID- 10075141
TI  - Cardioprotection by opening of the K(ATP) channel in unstable angina. Is this a
      clinical manifestation of myocardial preconditioning? Results of a randomized
      study with nicorandil. CESAR 2 investigation. Clinical European studies in angina
      and revascularization.
AB  - AIMS: To assess the anti-ischaemic and anti-arrhythmic effects and overall safety
      of nicorandil, an ATP sensitive potassium (K+) channel opener, with
      'cardioprotective' effects, in patients with unstable angina. METHODS: In a
      multicentre, randomized, double-blind, parallel-group, placebo-controlled study,
      oral nicorandil 20 mg twice daily or a matching placebo was administered for a
      minimum of 48 h to patients admitted with unstable angina. Treatment was
      standardized to include, where tolerated, oral aspirin, a beta-blocker and
      diltiazem. Continuous Holter ECG monitoring was performed for 48 h to assess the
      frequency and duration of transient myocardial ischaemia and any tachyarrhythmia,
      as the predefined end-points of the study. A pain chart recorded the incidence
      and severity of chest pain throughout the study period. Patients with myocardial
      infarction identified retrospectively from troponin-T analysis were excluded.
      RESULTS: Two hundred and forty-five patients were recruited into the study. Forty
      three patients were excluded with an index diagnosis of myocardial infarction,
      two were not randomized and 12 had unsatisfactory tape data. In the remaining 188
      patients, six out of 89 patients (6.7%) on nicorandil experienced an arrhythmia,
      compared with 17 out of 99 patients (17.2%) on placebo (P=0.04). Three nicorandil
      patients experienced three runs of non-sustained ventricular tachycardia compared
      to 31 runs in 10 patients on placebo (P=0.087 patients; P<0.0001 runs). Three
      nicorandil patients had four runs of supraventricular tachycardia, compared to 15
      runs in nine patients on placebo (P=0.14 patients; P=0.017 runs). Eleven (12.4%)
      patients on nicorandil had 37 episodes of transient myocardial ischaemia (mostly
      silent) compared with 74 episodes in 21 (21.2%) patients on placebo (P=0.12
      patients; P=0.0028 episodes). In the overall safety analysis, which included all
      patients who received at least one dose of study medication, there were no
      significant differences in the rates of myocardial infarction or death between
      the nicorandil or placebo-treated groups. CONCLUSIONS: Nicorandil, added to
      aggressive anti-anginal treatment for unstable angina, reduces transient
      myocardial ischaemia, non-sustained ventricular, and supraventricular arrhythmia
      compared to placebo. The anti-arrhythmic activity with nicorandil is probably a
      secondary effect resulting from its anti-ischaemic action and we suggest that
      this may be related to its effect on the ATP sensitive potassium channel causing
      pharmacological preconditioning.

PMID- 10075142
TI  - A randomized placebo-controlled trial of fluvastatin for prevention of restenosis
      after successful coronary balloon angioplasty; final results of the fluvastatin
      angiographic restenosis (FLARE) trial.
AB  - BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase
      inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non
      sterol compounds involved in cell proliferation. Experimental evidence suggests
      that fluvastatin may, independent of any lipid lowering action, exert a greater
      direct inhibitory effect on proliferating vascular myocytes than other statins.
      The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate
      the ability of fluvastatin 40 mg twice daily to reduce restenosis after
      successful coronary balloon angioplasty (PTCA). METHODS: Patients were randomized
      to either placebo or fluvastatin 40 mg twice daily beginning 2-4 weeks prior to
      planned PTCA and continuing after a successful PTCA (without the use of a stent),
      to follow-up angiography at 26+/-2 weeks. Clinical follow-up was completed at 40
      weeks. The primary end-point was angiographic restenosis, measured by
      quantitative coronary angiography at a core laboratory, as the loss in minimal
      luminal diameter during follow-up. Clinical end-points were death, myocardial
      infarction, coronary artery bypass graft surgery or re-intervention, up to 40
      weeks after PTCA. RESULTS: Of 1054 patients randomized, 526 were allocated to
      fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427
      in the placebo group were included in the intention-to-treat analysis, having
      undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the
      time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was
      maintained at 33% at 26 weeks. There was no difference in the primary end-point
      between the treatment groups (fluvastatin 0.23+/-0.49 mm vs placebo 0.23+/-0.52
      mm, P=0.95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%,
      chi-square P=0.42), or in the incidence of the composite clinical end-point at 40
      weeks (22.4% vs 23.3%; logrank P=0.74). However, a significantly lower incidence
      of total death and myocardial infarction was observed in six patients (1.4%) in
      the fluvastatin group and 17 (4.0%) in the placebo group (log rank P=0.025).
      CONCLUSION: Treatment with fluvastatin 80 mg daily did not affect the process of
      restenosis and is therefore not indicated for this purpose. However, the observed
      reduction in mortality and myocardial infarction 40 weeks after PTCA in the
      fluvastatin treated group has not been previously reported with statin therapy.
      Accordingly, a priori investigation of this finding is indicated and a new
      clinical trial with this intention is already underway.

PMID- 10075143
TI  - Study on propionyl-L-carnitine in chronic heart failure.
AB  - AIMS: In patients with chronic heart failure, fatigue is independent of
      haemodynamic and neuroendocrine changes and possibly may be due to impaired
      muscle metabolism. Propionyl-L-carnitine, a carnitine derivative, was shown in
      previous studies to improve muscle metabolism. The objective of this study was to
      evaluate the effect of propionyl-L-carnitine on exercise capacity in mild
      moderate chronic heart failure patients, treated with ACE inhibitors and
      diuretics. METHODS AND RESULTS: This was a phase III, double-blind, randomized,
      parallel, multicentre study. The primary objective was the evaluation of the
      effect of propionyl-L-carnitine vs placebo on maximum exercise duration using a
      bicycle exercise test. The primary analysis performed in the intention-to-treat
      population (271 and 266 patients in propionyl-L-carnitine and placebo), showed no
      statistically significant difference between treatments. A difference of 15 s in
      favour of propionyl-L-carnitine was observed in the completer/complier population
      (P=0.092). An a priori specified subgroup analysis on patients stratified by
      baseline maximum exercise duration showed a trend of improvement in propionyl-L
      carnitine patients with shorter maximum exercise duration. A non a priori
      specified analysis in patients stratified by ejection fraction (< or = 30% vs 30
      40%), showed a statistically significant difference in maximum exercise duration
      in favour of propionyl-L-carnitine in those patients with a higher ejection
      fraction (40 s, P<0.01). There were no safety issues. CONCLUSION: The study fails
      to meet the primary objective, but confirms the good safety profile of propionyl
      L-carnitine. An exploratory non-prespecified analysis suggests that propionyl-L
      carnitine improves exercise capacity in patients with preserved cardiac function.
      This hypothesis needs to be confirmed by a specific tailored study.

PMID- 10075144
TI  - Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp
      and trigeminal ganglion.
AB  - Numerous nerve fibres containing calcitonin gene-related peptide (CGRP) were
      found by immunocytochemistry in human molar pulp. These nerves were often seen
      around small blood vessels and as free endings without vascular contact. In the
      trigeminal ganglion a large number of CGRP-immunoreactive nerve-cell bodies,
      mostly of small to medium size, was encountered. Reverse transcriptase-polymerase
      chain reaction, using specific sense and antisense primers, detected mRNA
      expression of the human CGRP1 receptor in the pulp tissue and the trigeminal
      ganglion. Thus, both CGRP-containing nerve fibres and CGRP1 receptor mRNA are
      present in human tooth pulp, where they may be involved in the regulation of
      vascular tone and other local reactions to injury.

PMID- 10075145
TI  - Deciduous tooth size and morphogenetic fields in children from Christ Church,
      Spitalfields.
AB  - Deciduous tooth dimensions of a recent archaeological sample of 37 boys, 18 girls
      and 88 children of unknown sex from London were measured. Mesiodistal (maximum
      breadth at the contact point) and buccolingual measurements were recorded. A
      gradient of size variation was apparent with anterior teeth showing the highest
      variation and second molars the least. In general, the teeth of the children of
      Spitalfields were smaller than those of other groups from various archaeological
      and contemporary populations. Fluctuating asymmetry between left- and right-hand
      sides was greatest for the lateral incisor. Asymmetry of the mesiodistal
      dimension of the upper central incisor differed significantly from the
      buccolingual dimension (p < 0.01). Tooth size in both dimensions was generally
      larger in boys than in girls. The maxillary lateral incisor displayed significant
      dimorphism in the mesiodistal dimension (p < 0.05). The second molars (both upper
      and lower) were less variable and less asymmetrical than the first molars,
      suggesting that the second molar may be the key tooth of the deciduous molar
      field.

PMID- 10075146
TI  - Postnatal changes of gene expression for tissue inhibitors of metalloproteinase-1
      and -2 and cystatins S and C, in rat submandibular gland demonstrated by
      quantitative reverse transcription-polymerase chain reaction.
AB  - The rat submandibular gland is not fully developed at birth and definitive
      differentiation takes place postnatally. The steady-state mRNA expression for the
      four proteinase inhibitor molecules, tissue inhibitors of metalloproteinase
      (TIMP)-1 and -2, and cystatins S and C, and for a housekeeping gene,
      glyceraldehyde-3-phosphate dehydrogenase (G3PDH), in rat submandibular glands was
      measured by quantitative competitive reverse transcription-polymerase chain
      reaction (RT-PCR) at different stages of postnatal development. The gene
      expression patterns of TIMP-1 and -2 relative to G3PDH were similar to each
      other. The TIMP-2 and cystatin C genes were more highly expressed than those of
      TIMP-1 and cystatin S at all stages. Moreover, the gene expressions of TIMP-1 and
      -2, and of cystatins S and C, were predominant between 1 and 7, and 7 and 12
      weeks of age, respectively, and coincided developmentally with the regression of
      terminal tubule cells and the differentiation of granular convoluted tubule
      cells, respectively. Quantitative competitive RT-PCR allowed accurate measurement
      of small changes in the steady-state concentrations of these proteinase-inhibitor
      mRNA molecules.

PMID- 10075147
TI  - Development of inflammation after application of mustard oil or glutamate to the
      rat temporomandibular joint.
AB  - Application of the small-fibre excitant and inflammatory irritant mustard oil or
      the excitatory amino-acid receptor agonist glutamate to the rat temporomandibular
      joint (TMJ) region evokes similar changes in jaw-muscle activity, suggesting that
      peripheral application of glutamate may be nociceptive. Application of mustard
      oil to the TMJ region is also inflammatory, but, it is not clear if application
      of glutamate is equally inflammatory. In this study the extent of plasma-protein
      extravasation and oedema induced by mustard oil application to the TMJ region was
      compared with that induced by glutamate. Application of mustard oil resulted in
      plasma-protein extravasation into the TMJ tissues and oedema of the TMJ region.
      In contrast, glutamate did not cause plasma-protein extravasation or oedema.

PMID- 10075148
TI  - Effects of caffeine on fluoride, calcium and phosphorus metabolism and calcified
      tissues in the rat.
AB  - This 6-week study was designed to determine the effects of graded doses of
      caffeine intake (3, 25 or 100 mg/kg per day) on the metabolic balance and tissue
      concentrations of fluoride, calcium and phosphorus in Sprague-Dawley rats.
      Caffeine intake did not affect the absorption, urinary excretion or balance of
      fluoride, the plasma, bone or enamel concentrations of fluoride, nor the
      occurrence of incisor enamel fluorosis. Neither did it affect the metabolism of
      calcium or phosphorus except that the urinary excretion of calcium was increased.
      This effect, however, was not sufficient to influence significantly calcium
      balance. The ash content of the femur epiphysis and bone mineral content of the
      tibia were significantly reduced only in the group exposed to the highest dose of
      caffeine. These effects on bone were not significantly related to the balance of
      calcium or phosphorus. It was concluded that caffeine, even at an extremely high
      level of intake, has no detectable effect on the balance or tissue concentrations
      of fluoride, calcium or phosphorus in the rat.

PMID- 10075149
TI  - Differential activation by cytokines of mitogen-activated protein kinases in
      bovine temporomandibular-joint disc cells.
AB  - Temporomandibular disorders affect a significant proportion of the population.
      While their aetiology is not well defined, recent histological studies suggest
      that the majority are similar to the osteoarthritis seen in other joints.
      Inflammatory cytokines such as interleukin-1 and tumour necrosis factor-alpha
      appear to be important in the cascade of events leading to joint destruction in
      osteoarthritis. Here, cells from the disc of bovine temporomandibular joint were
      used to examine the response to various cytokines in vitro. Disc cells were
      stimulated with interleukin-1alpha, tumour necrosis factor-alpha, transforming
      growth factor-beta, platelet-derived growth factor, and basic fibroblast growth
      factor. Their effects were monitored by assessing the phosphorylation of selected
      signal-transduction intermediates using western blot. Mitogen-activated protein
      kinases (Erk 1, Erk 2) were rapidly phosphorylated by exposure to basic
      fibroblast growth factor, platelet-derived growth factor, and tumour necrosis
      factor-alpha, while interleukin-1alpha showed a weak response. Transforming
      growth factor-beta failed to activate these kinases. Examination of the effect of
      these cytokines on p38 (an intermediate in the stress-activated protein-kinase
      pathway) showed an increase in phosphorylated p38 when stimulated with tumour
      necrosis factor-alpha and interleukin-1alpha. The amounts of phosphorylated
      signal transducer and activator of transcription-3 did not significantly increase
      when the cells were exposed to any of the cytokines.

PMID- 10075150
TI  - Immunohistochemical localization of metallothionein in the developing teeth of
      cadmium-injected rats.
AB  - The ability of cadmium (Cd) to induce the synthesis of metallothionein (MT) in
      the developing teeth of the rat was investigated. Rats were given daily
      intraperitoneal injections of cadmium chloride (1.5 mg Cd/kg) for 7 days. The
      induction of MT synthesis in incisor teeth after Cd treatment was investigated
      immunohistochemically using a polyclonal antibody to MT. Immunoreactivity to MT
      was observed in the papillary layer of epithelial cells of the secretory zone, in
      one layer of epithelial cells of the presecretory zone and within ameloblasts of
      the postsecretory zone. Normal control rats did not exhibit MT staining. These
      results indicate that Cd induces MT synthesis within specific epithelial cells of
      the enamel organ of the rat. It is proposed that these findings demonstrate an
      adaptive cellular mechanism that protects these cells from cadmium toxicity.

PMID- 10075151
TI  - Expression of bone-resorptive and regulatory cytokines in murine periapical
      inflammation.
AB  - Periapical bone destruction earlier was shown to be mediated primarily by
      interleukin (IL)-1alpha in a rat model. The production and action of IL-1alpha is
      in turn potentially modulated by a network of cytokines, which are produced by
      infiltrating T-helper type 1 (Th1) and type 2 (Th2) lymphocytes, and resident
      connective tissue cells within the lesion. This study was designed to examine the
      kinetics of expression of 10 cytokines in experimentally induced murine
      periapical lesions, including bone-resorptive [IL-1alpha, tumour necrosis factor
      alpha (TNFalpha), IL-6, IL-11], Th1-type [IL-2, IL-12, interferon-gamma
      (IFNgamma)] and Th2-type (IL-4, IL-6, IL-10, IL-13) mediators. Cytokine mRNA
      expression was assessed qualitatively by reverse transcription-polymerase chain
      reaction, and cytokine proteins quantified by enzyme-linked immunosorbent assay.
      IL-1alpha and TNFalpha protein and mRNA were highly expressed, beginning on day
      7, and increased to day 28. IL-6 increased to day 14 and then declined, whereas
      the expression of IL-11 was not modulated by pulp exposure. Most of the Th1-type
      cytokines, including IL-2, IL-12, and IFNgamma, showed an increase in mRNA and/or
      protein expression in periapical lesions after pulpal exposure; the expression of
      Th2-type cytokines was similarly increased, but had declined at the latest time
      point (day 28), suggesting possible inhibition by Th1-type mediators. Significant
      correlations were observed between levels of IL-1alpha and Th1-derived pro
      inflammatory mediators IL-2, IL-12, TNFalpha, and IFNgamma. There was a lack of
      correlation between IL-1alpha and Th2-type anti-inflammatory mediators, including
      IL-4, -6, and -10. These results indicate that a cytokine network is activated in
      the periapex in response to bacterial infection, and that Th1-modulated pro
      inflammatory pathways may predominate during periapical bone destruction.

PMID- 10075152
TI  - Enhanced expression of activation-associated molecules on macrophages of
      heterogeneous populations in expanding periapical lesions in rat molars.
AB  - Exudative macrophages are the most prevalent inflammatory cells during the entire
      pathogenetic process in experimentally induced rat periapical lesions. To clarify
      the significance of macrophages in the pathogenesis of periapical lesions, the
      way in which the phenotype of ED1 (a general marker for mononuclear phagocytes)
      positive cells is modulated in actively expanding lesions was investigated, by
      immunoperoxidase staining with a panel of antibodies that recognize several
      activation-associated molecules on macrophages. Periapical lesions were induced
      experimentally by exposing the pulp in the lower first molars of Wistar rats.
      Active lesion expansion with morphological diversification of ED1-positive cells
      occurred between 14 and 28 days after the injury. Double immunoperoxidase
      staining revealed that ED1-positive cells coexpressing class II molecules of the
      major histocompatibility complex (MHC) molecules, inducible nitric oxide synthase
      (iNOS) and/or CD11a increased during the period of active lesion expansion.
      Increases of endothelial cells expressing intracellular adhesion molecule-1 and
      CD25 (interleukin-2 receptor)-expressing lymphocytes were also seen during the
      same period. Moreover, there existed two particular subpopulations of ED1 + cells
      in the established lesion at 28 days: (1) ED1++/class II MHC - /iNOS+ cells,
      located around the periapical abscess, and (2) ED1+/class II MHC+/ iNOS- cells
      with slender or dendritic morphology, distributed predominantly in the outer
      portion of the lesion where T lymphocytes were abundant. The first cell type
      could be a macrophage with potent phagocytic and antimicrobial actions, and the
      second might possess sufficient antigen-presenting capacity to cause the
      activation of T lymphocytes. It was concluded that macrophages, when activated,
      may participate in triggering lesion expansion. Functionally distinct
      subpopulations of macrophages may occupy different sites within the lesion where
      they can most effectively exert their specific functions.

PMID- 10075153
TI  - Recruitment of osteoclasts in the mandibular condyle of growing osteopetrotic
      (op/op) mice after a single injection of macrophage colony-stimulating factor.
AB  - The purpose was to elucidate histological changes in the mandibular condyle and
      ramus in growing osteopetrotic (op/op) mice after a single injection of
      macrophage colony-stimulating factor (M-CSF). M-CSF (5 microg) was injected into
      6-, 11-, 26-, 56- and 86-day-old op/op mice, and the mice were killed 4 days
      after the injection. In normal mice, the condyle was substantially wider than the
      ramus beneath it, and enlargement and ossification of the condyle occurred after
      weaning. These changes were not found in the uninjected and injected op/op mice,
      the condyles of which were occupied by hypertrophic cartilage cells, and the
      hypertrophic cell layer was thicker and more irregular in the arrangement of
      epiphyseal cell columns. In spite of the lack of bone resorption in uninjected
      and injected op/ op mice, ossification of the mandibular ramus occurred, but
      later than that of normal mouse. The number of tartrate-resistant acid
      phosphatase-positive cells in the injected op/op and normal mice approached a
      maximum at 30 days and then gradually decreased up to 90 days of age, although
      the numbers were substantially different for all ages. The uninjected op/op mice
      had no visible osteoclasts until 15 days and their number then increased
      significantly from 60 to 90 days of age. These results were considered due to the
      difference in biological responses of bony structures to M-CSF injection in the
      op/op mice. The influences of mechanical stimuli from masticatory functions,
      which are deficient in op/op mice, might also be responsible for the differences
      in bony architecture between the op/op and normal mice.

PMID- 10075154
TI  - Stimulation by low concentrations of fluoride of the proliferation and alkaline
      phosphatase activity of human dental pulp cells in vitro.
AB  - Fluoride has been used for decades, either systemically or topically, to prevent
      dental caries. The purpose of this study was to clarify the effects of low
      concentrations of fluoride on proliferation, differentiation and extracellular
      matrix synthesis in normal human dental pulp cells (DP-1 and DP-2) in vitro. The
      effects were compared with those on a human osteoblastic osteosarcoma cell line,
      TE-85. Fluoride at micromolar concentrations significantly and dose-dependently
      stimulated [3H]thymidine incorporation into DNA in DP-1, DP-2 and TE-85 cells,
      with optimal effects around 50 microM, by 127 +/- 7%, 124 +/- 0.6% and 152 +/-
      13.4%, respectively. To assess the potential influence of fluoride on cell
      differentiation, the effects of mitogenic concentrations on alkaline phosphatase
      activity were measured. Fluoride significantly increased the enzyme's activity in
      DP-1 and TE-85 by 177 +/- 12% and 144 +/- 12.3%. To evaluate the effect on
      extracellular-matrix synthesis, the synthesis of type I collagen was indirectly
      determined by an assay of procollagen type I c-peptide production. Fluoride
      significantly increased that production by 150 +/- 8.7% in TE-85, but not in
      either DP-1 or DP-2. These observations suggest that fluoride, if used at low
      concentrations, could be a useful therapeutic agent where increased regeneration
      of dentine is desired, such as after pulp amputation, by stimulating the
      proliferation and differentiation of the dental pulp cells.

PMID- 10075155
TI  - The effect of repeated sampling on paraffin-stimulated salivary flow rates in
      menopausal women.
AB  - Paraffin-stimulated whole-saliva samples of 12 post- and perimenopausal women
      were taken five times over a 7-week period. After 1 min of prestimulation, saliva
      was collected for 5 min under standardized conditions. Saliva was first collected
      on three consecutive days, and two additional samples were collected 6 and 7
      weeks after the first. Salivary flow rates showed significant variation between
      samplings. The greatest difference appeared between the first and second
      collections. The increase in flow rates between these collections was significant
      (p = 0.003). The third successive collection also gave a significantly (p =
      0.005) higher flow rate than the first. The 6-week and baseline samples were
      similar. The 7-week sample showed a significantly higher flow rate (p = 0.018)
      compared with the baseline value. These results stress the importance of
      standardization of sampling intervals when salivary flow rates are studied.

PMID- 10075156
TI  - Mumps component in combined measles, mumps, and rubella vaccines.

PMID- 10075157
TI  - The stability and immunogenicity of a protein antigen encapsulated in
      biodegradable microparticles based on blends of lactide polymers and polyethylene
      glycol.
AB  - Protein-loaded microparticles were produced from blends of poly(ethylene glycol)
      (PEG) with poly(L-lactide) (PLA) homopolymer or poly(DL-lactide co-glycolide)
      copolymers (PLG) using a water-in oil-in oil method. The stability of ovalbumin
      (OVA) associated with microparticles prepared using PEG and 50:50 PLG, 75:25 PLG
      and PLA, respectively, was analysed by SDS-PAGE and quantified by scanning
      densitometry following incubation in PBS at 37 degrees C for up to 1 month.
      Fragmentation and aggregation of OVA was detected with all 3 formulations. The
      extent of both processes correlated with the degradation rate of the lactide
      polymer used and decreased in the order PLA < 75:25 PLG < 50:50 PLG. Extensive
      degradation of the PLG/PEG microparticles also occurred over 4 weeks whereas the
      use of PLA/PEG blends resulted in a stable microparticle morphology and much
      reduced fragmentation and aggregation of the associated protein. Following a
      single sub-cutaneous immunisation, high levels of specific serum IgG antibody
      were elicited by OVA associated with the PLA/PEG particles. Injection of OVA
      associated with the 75:25 PLG/PEG microparticles resulted in very low levels of
      specific antibody. A higher response was induced by the 50:50 PLG/PEG formulation
      but there was very large inter-animal variation in this group. Antibody levels
      elicited by all 3 formulations were significantly higher than those elicited by a
      single injection of soluble OVA. Analysis of antigen specific IgG1 and IgG2a
      antibody subtype levels also revealed the greater efficacy of the PLA/PEG
      microparticles as an adjuvant system. The use of PLA/PEG microparticles shows
      improved protein loading and delivery capacity while maintaining a high level of
      stability of the associated protein. These results indicate a strong correlation
      between the stability of microencapsulated antigen and the magnitude of the
      immune response following sub-cutaneous immunisation.

PMID- 10075158
TI  - Measles immunity and vaccination policy in Catalonia.
AB  - The prevalence of antibodies against measles in a representative sample of the
      school population in Catalonia was established and the results compared with
      previous studies. The study was carried out in 1996 using blood samples obtained
      from schoolchildren aged 6-7 years, 10-11 years, 13 14 years and 15-16 years.
      1231 schoolchildren were studied. The global prevalence of antibodies was 96.3%,
      and a considerable increase was observed with respect to the prevalence in 1986
      (89.4%). The level of antibodies was 94% at 6-7 years and 10-11 years, 99.7% at
      13-14 years and 98.3% at 15 16 years. These data would suggest the advancement of
      the administration of the second dose of measles-mumps rubella vaccine to 4 6
      years instead of at 11 years.

PMID- 10075159
TI  - Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide
      from beta-2-microglobulin elicits a protective and DTH response to herpes simplex
      virus type 1.
AB  - A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine
      containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322
      332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited
      protection from intraperitoneal viral challenge and promoted DTH responses. The
      H1 peptide and other H1 containing heteroconjugates did not elicit protection or
      DTH responses. Antibody to the H1 peptide could not be detected by ELISA
      following vaccination with peptide, heteroconjugate or natural infection. The
      LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently
      boosted by infection. These studies show that attachment of the J peptide can
      make a CTL epitope into a vaccine which is immunogenic and promotes a protective
      Th1 type of response.

PMID- 10075160
TI  - A comparative study of PENTA vaccine booster doses given at 12, 15, or 18 months
      of age.
AB  - For infants immunized with Haemophilus influenzae type b conjugate vaccines,
      booster immunization is usually recommended in the second year of life, typically
      between 12 and 18 months. This study assessed the effect of age at booster
      immunization on pre-immunization antibody trough levels and on subsequent
      responses, for a PRP-T conjugate vaccine. Subjects were healthy children who had
      received PENTA vaccine (DPT-IPV/PRP-T combination) as infants. They were enrolled
      and given measles-mumps-rubella vaccine (MMR) at 12 months of age, then randomly
      assigned to receive PENTA vaccine concurrently with MMR or at 15 or 18 months of
      age. Parents were asked to note any adverse effects after PENTA vaccination.
      Blood samples were obtained prior to PENTA vaccination and 4 weeks later, and
      tested for antibodies to each antigen. In total 253 children received PENTA
      vaccine: 86 at 12 months, 85 at 15 months and 82 at 18 months. Injection site
      redness and swelling were least extensive in the youngest group (p < 0.001) but
      their rates of occurrence did not differ with age. Anti-PRP levels were similar
      in each age group prior to immunization; post-booster geometric mean
      concentrations (GMCs) ranged from 13.0 microg/ml in the youngest to 33.9
      microg/ml in the oldest subjects (p < 0.0001). For each of the other antigens
      examined, booster responses were strongest at 18 months. We conclude that anti
      PRP levels are stable between 12 and 18 months in children previously given PRP-T
      vaccine. PENTA boosters given at 12 months appear to cause milder injection site
      morbidity whereas those given at 18 months result in stronger responses to
      virtually every constituent antigen, although each age group responded
      satisfactorily.

PMID- 10075161
TI  - Efficacy of SAG-2 oral rabies vaccine in two species of jackal (Canis adustus and
      Canis mesomelas).
AB  - Trials were carried out to test the efficacy of SAG-2 oral rabies vaccine in two
      species of jackals, namely the side-striped jackal (C. adustus) and the black
      backed jackal (C. mesomelas). The first trial tested the efficacy of SAG-2 when
      given by direct oral administration at doses of 6.5 and 7.5 log10 median tissue
      culture infectious doses (TCID50). One side-striped jackal which had received the
      higher dose did not seroconvert and succumbed to challenge, while all other
      jackals seroconverted and resisted a lethal challenge. The second trial tested
      the efficacy in side-striped jackals only of the SAG-2 vaccine when given within
      chicken head baits. A volume of 1.8 ml of vaccine fluid with titers of 7.0 or 8.0
      log10 TCID50/ml were placed into blisters which were stapled under the skin of
      the chicken heads. All jackals (5/5) which received 8.0 log10 TCID50/ml and 3 of
      5 which received 7.0 log10 TCID50/ml seroconverted and resisted lethal challenge.
      A third trial tested the rate of vaccine virus titer loss in chicken head baits
      placed under field conditions. Titer loss was marked in baits which were not
      protected from direct sunshine, whereas under vegetation cover approximately
      log10 TCID50/ml was lost every 3 days. Hence, it was concluded that a bait
      vaccine virus titer of 8.0 log10 TCID50/ml will be sufficient to immunize wild
      jackal populations if enough baits can be consumed by jackals within 3 days. This
      conclusion needs to be tested through the use of oral vaccine in field trials.

PMID- 10075162
TI  - Infection, immunisation and atherosclerosis: is there a link?
AB  - Atherosclerosis is the predominant underlying pathology responsible for coronary
      heart disease (CHD). It bears all the hallmarks of a chronic inflammatory disease
      and typical atherosclerotic lesions contain activated macrophages and T-cells.
      There have been several reports of possible associations between prior exposure
      to a number of specific micro-organisms and subsequent CHD, and prospective
      epidemiological studies have reported that elevated plasma levels of particular
      acute phase reactants (APRs) are predictors of future cardiac events.
      Investigators have also shown that immunisations exacerbate atherosclerosis in
      experimental animal models. These data raise the possibility that
      immunostimulation associated with natural infection by certain organisms, or
      vaccination, may promote atherosclerosis. A hypothesis which may explain all
      these findings, is that the cellular--and perhaps humoral--responses associated
      with immune stimulation may enhance atherogenesis.

PMID- 10075163
TI  - An aerosol challenge model of Bordetella pertussis infection as a potential
      bioassay for acellular pertussis vaccines.
AB  - Whole cell and five different types of acellular pertussis vaccine were assayed
      using a mouse aerosol challenge model which permitted delivery of a controlled,
      consistent dose of Bordetella pertussis to the lower respiratory tract. Using
      this system, the viable counts in the lungs of vaccinated mice were immunisation
      dose-dependent and allowed the protective capacity of different vaccine
      preparations to be distinguished. This model may thus provide the basis for a
      protection assay for pertussis vaccines. Comparison of acellular vaccines with a
      whole cell pertussis vaccine showed that the latter gave better active protection
      in mice but with a different dose-response relationship. Thus the two types of
      vaccine are not directly comparable in the same assay and require different
      reference standards. A pentavalent type acellular vaccine is suggested as a
      possible candidate standard for the acellular vaccine potency test. The results
      suggest that this aerosol challenge model has potential for use as a potency test
      for acellular pertussis vaccines.

PMID- 10075164
TI  - A peptide construct containing B-cell and T-cell epitopes from the foot-and-mouth
      disease viral VP1 protein induces efficient antiviral protection.
AB  - A new peptide construct Palm135-158-GGA-170-188(Acm) has been synthesized and
      investigated in a number of in vitro and in vivo test systems. The construct
      contains a virus specific T-helper epitope within the 170-188 sequence of VP1, in
      addition to the main antigenic 135-158 region of the foot-and-mouth disease viral
      VP1 protein (strain A22). The construct has higher protective, antigenic,
      immunogenic and T-cell proliferative activity then the previously described
      shorter peptide Palm(2)135-159. The 170-188 part of the construct serves as a
      virus specific T-epitope, responsible for the enhanced immunogenic and protective
      activity of the construct.

PMID- 10075165
TI  - Safety and immunogenicity of hepatitis A vaccine in infants: a candidate for
      inclusion in the childhood vaccination programme.
AB  - Forty-eight infants received a single dose (720 ELISA units = 0.5 ml) of
      inactivated hepatitis A vaccine at the fifth month of age with booster at the
      11th month of age, together with the second and third doses of the vaccines
      compulsory under Italian law (diphtheria, tetanus, oral polio and hepatitis B).
      Overall, the seroconversion rate was 100%. The anti-HAV geometric mean titre
      (GMT) reached 3,021 mIU/ml in infants born to anti-HAV-negative mothers, but only
      399 mIU/ml in infants born to anti-HAV-positive mothers. Hepatitis A vaccine was
      immunogenic, safe and well tolerated without significant side-effects. There
      seems to be no reason for not including it in childhood vaccination programmes
      particularly in low endemic HAV areas.

PMID- 10075166
TI  - Effective induction of HIV-specific CTL by multi-epitope using gene gun in a
      combined vaccination regime.
AB  - Reliable and effective induction of cytotoxic T-lymphocytes (CTL) is one of the
      prime objectives of vaccine research. Previously, novel HIV vaccine candidates
      were constructed as a string of CTL epitopes (20 human, 3 macaque and 1 mouse)
      delivered using a DNA vector [Hanke T, Schneider J, Gilbert SG, Hill AVS,
      McMichael A. DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum:
      immunogenicity in mice. Vaccine 1998;16:426-435.] or modified vaccinia Ankara
      (MVA [Hanke T, Blanchard TJ, Schneider J, Ogg GS, Tan R, Becker MSC, Gilbert SG,
      Hill AVS, Smith GL, McMichael A. Immunogenicities of intravenous and
      intramuscular administrations of MVA-based multi-CTL epitope vaccine for HIV in
      mice. J Gen Virol 1998;79:83-90.]), i.e. vaccine vehicles acceptable for use in
      humans. In mice, a single intramuscular (i.m.) needle injection of either vaccine
      alone elicited good CTL responses. Here, it is demonstrated that the multi
      epitope DNA also induced CTL when delivered intradermally using the Accell gene
      gun. The CTL responses increased after re-immunization and after three deliveries
      were comparable to those induced by a single i.m. injection. Recent evidence
      indicates that combining routes and vaccine vehicles enhances the immunogenicity
      of vaccine-delivered or -encoded antigens. Here, it is shown that administration
      of DNA by an i.m. priming/gene gun boosting more efficiently induced CTL than
      gene gun priming/i.m. boosting. A similar increment was obtained by sequential
      vaccinations using a gene gun-delivered DNA followed by recombinant MVA. Thus
      particular sequences of routes or vaccine vehicles rather than simple prime-boost
      delivery of a single vaccine is critical for an effective elicitation of CTL.

PMID- 10075167
TI  - The use of Toxorhynchites splendens for identification and quantitation of
      serotypes contained in the tetravalent live attenuated dengue vaccine.
AB  - Assurance of identity and quantity is an indispensable part of quality control in
      the manufacture of vaccines. Dengue-1 PDK13, dengue-2 PDK53, dengue-3 PGMK30F3
      and dengue-4 PDK48 in the live attenuated tetravalent dengue vaccine were assayed
      by identification and quantitation in a mosquito system (Toxorhynchites
      splendens). Each serotype of dengue virus was identified by dengue specific
      monoclonal antibodies in the indirect fluorescent antibody test. Virus content
      was estimated by calculating the 50% mosquito infectious dose (MID50).
      Differences from 0 to +/-0.5 log10 were observed between the original monovalent
      titer and that from the blend which showed no significant difference at 95%
      confidence limit (P < 0.05). This result indicates that there is no interference
      between dengue serotypes in mosquitoes infected by intrathoracic inoculation with
      the virus mixture. It can be also concluded that this mosquito system can be used
      as an effective measure for infectivity titration of each component in the
      tetravalent dengue vaccine.

PMID- 10075168
TI  - Hepatitis B vaccination in mentally retarded: effectiveness after 11 years.
AB  - The long-term effectiveness of hepatitis B vaccination was determined in a high
      risk group of 105 institutionalized mentally retarded. All individuals were
      vaccinated in 1986, with three (0, 1, 6 months), four (0, 1, 6 and 12 months) or
      more doses according to their immune response at month 7, resulting in group 1
      (G1), group 2 (G2) and group 3 (G3). They were annually followed up for five
      years, after which they received a booster dose. Eleven years after the initial
      vaccination, they were again tested for the presence of hepatitis B virus (HBV)
      serologic markers. The decline in anti-HBs logtitre over the first five years was
      51% for G1 and 45% for G2. From the booster on month 60 to year 11, the overall
      decline was 31%. Eleven years after the start of vaccination and six years after
      the booster, 92% of the individuals had protective antibody levels higher than 10
      IU/L. G1 had a geometric mean titre of 2015 IU/L, for G2 this was 245 IU/L. The
      difference in response to vaccination between the groups did not affect their
      protection. Only two vaccinees seroconverted to anti-HBc positivity without
      becoming carrier or ill. Long-term protection against HBV by vaccination appears
      to be excellent.

PMID- 10075169
TI  - Induction of mucosal and systemic immune response by oral immunization with H.
      pylori lysates encapsulated in poly(D,L-lactide-co-glycolide) microparticles.
AB  - Helicobacter pylori is a major cause of chronic antral gastritis and peptic ulcer
      diseases. Several kinds of poly(D,L-lactide-coglycolide) microparticles
      containing H. pylori whole-cell lysate (PLG-HP) were prepared by the solvent
      evaporation method using double emulsion. Physical properties, such as particle
      size, protein content, and morphology were investigated. All prepared
      microparticles showed a smooth surface morphology from 0.5-0.86 microm in
      diameter and high degree of encapsulation efficiency from 62-75%. SDS-PAGE and
      immunoblotting of extracted antigen confirmed that the molecular weight and
      antigenicity of the antigen remained unaltered by the encapsulation procedure.
      Following the oral immunization of the microparticles to mice, antibody
      production was assayed in serum and gut washings by ELISA and antibody secreting
      cells were determined in intestinal lamina propria lymphocytes (LPL) by ELISPOT.
      Multiple oral immunizations induced significant H. pylori-specific intestinal IgA
      response as well as serum IgG response than those detected with soluble antigen
      (P < 0.001). The presence of antibody-secreting cell in intestinal lamina propria
      lymphocytes (LPL) was correlated with IgA level in gut washing fluids. After
      boosting at week-8, the antibody induction levels were highly increased
      irrespective of microparticles prepared with different PLG molecular weights.
      These data suggested that PLG-HP could stimulate the H. pylori-specific mucosal
      and systemic response in vivo and might be useful adjuvant in future H. pylori
      vaccine development.

PMID- 10075170
TI  - The influence of personal care and assistive devices on the measurement of
      disability.
AB  - The goal of all long-term care arrangements is to reduce the disabling effects of
      physical impairments and functional limitations. However, the means with which
      individuals cope with disability may not be equivalent and these differences may
      influence self-reports of disability in surveys. This paper examines assistive
      devices and personal care as factors in the measurement of disability among
      persons aged 70 and older in the community using the 1994 Survey of Asset and
      Health Dynamics of the Oldest Old (AHEAD) in the US. The use of assistive
      technology differs from personal care on a fundamental level. It does not require
      the ongoing cooperation or coordination of other people and therefore increases
      the sense of independence with which a disabled individual can meet their long
      term care needs. Results indicate that older individuals can expect to spend most
      of their remaining years in good functional health, but up to two-thirds of
      disabled years will be spent with unmet ADL needs. Among those who are disabled,
      those who use only equipment and no personal care report less residual difficulty
      with mobility than those who use personal assistance (either alone or in
      combination with equipment) but the use of equipment alone is most effective for
      those with the least severe limitations.

PMID- 10075171
TI  - Risk factors for functional status decline in community-living elderly people: a
      systematic literature review.
AB  - To lay the groundwork for devising, improving and implementing strategies to
      prevent or delay the onset of disability in the elderly, we conducted a
      systematic literature review of longitudinal studies published between 1985 and
      1997 that reported statistical associations between individual base-line risk
      factors and subsequent functional status in community-living older persons.
      Functional status decline was defined as disability or physical function
      limitation. We used MEDLINE, PSYCINFO, SOCA, EMBASE, bibliographies and expert
      consultation to select the articles, 78 of which met the selection criteria. Risk
      factors were categorized into 14 domains and coded by two independent
      abstractors. Based on the methodological quality of the statistical analyses
      between risk factors and functional outcomes (e.g. control for base-line
      functional status, control for confounding, attrition rate), the strength of
      evidence was derived for each risk factor. The association of functional decline
      with medical findings was also analyzed. The highest strength of evidence for an
      increased risk in functional status decline was found for (alphabetical order)
      cognitive impairment, depression, disease burden (comorbidity), increased and
      decreased body mass index, lower extremity functional limitation, low frequency
      of social contacts, low level of physical activity, no alcohol use compared to
      moderate use, poor self-perceived health, smoking and vision impairment. The
      review revealed that some risk factors (e.g. nutrition, physical environment)
      have been neglected in past research. This review will help investigators set
      priorities for future research of the Disablement Process, plan health and social
      services for elderly persons and develop more cost-effective programs for
      preventing disability among them.

PMID- 10075172
TI  - Disentangling the process of disablement.

PMID- 10075173
TI  - Selecting national items for the WHOQOL: conceptual and psychometric
      considerations.
AB  - The WHOQOL is a new measure designed to assess quality of life cross-culturally
      in health and health care. An international core of 276 items covering 29 facets
      of quality of life organised into 6 domains has been established conceptually and
      then assessed in psychometric terms. The method also allowed for the inclusion of
      extra national items to enable the concept of quality of life to be complete for
      each language and culture and to achieve conceptual equivalence between different
      language versions in participating centres. The present study investigates the
      properties of these national items using data obtained from 3740 participants
      world-wide, who completed the instrument in 10 of 16 original WHOQOL centres.
      Five statistical criteria were applied to 144 national items to examine their
      performance in competition with internationally agreed core items from the same
      facet, using data obtained from within that centre. Multi-dimensional scaling and
      cluster analysis was used to examine the structural relationship of national
      items within their own facet and directed their inclusion. Forty (29%) national
      items were selected and detailed examples demonstrate the selection methods used.
      They show how entirely new facets as well as individual items can be assessed for
      appending to the core WHOQOL-100. They also enable ambiguity to be resolved where
      there may be doubt about whether proposed items constitute part of an existing
      facet or justify a new one. Where national items are similar in more than one
      centre, a mechanism is provided whereby these items can be re-evaluated as
      candidates for inclusion in any future revision of the international core.
      Lastly, a case is identified that may provide justification for the establishment
      of national facets.

PMID- 10075174
TI  - Patterns of health seeking behavior during episodes of childhood diarrhea: a
      study of Tzotzil-speaking Mayans in the highlands of Chiapas, Mexico.
AB  - In Chiapas, Mexico, diarrheal disease causes the majority of all deaths in
      children under the age of five. Treatment of childhood diarrhea may be influenced
      by local beliefs and cultural practices. Few studies have attempted to
      quantitatively evaluate health seeking behavior (HSB) for diarrheal diseases in
      indigenous communities, while controlling for potential confounding factors such
      as parental education or socioeconomic status. A rapid ethnographic survey was
      conducted in Nabenchauc, Chiapas, to determine hypothetical HSB patterns for each
      of four major types of childhood diarrhea. Additionally, we examined the actual
      HSB for the last episode of childhood diarrheal illness within the household. One
      hundred households participated in the survey; 94 households with children < 5
      years old reported a mean of 1.9 diarrheal episodes during the preceding month.
      Households reported using a mean of 1.3 types of in-home remedies. Oral
      rehydration therapy (ORT) was used in <2% of the 368 HSB patterns elicited for
      the four types of diarrhea. HSB patterns utilized an eclectic combination of
      traditional, allopathic, local and distant health care options. A mean of 2.5
      outside-the-home health care options were reported for each diarrheal type; the
      local grocery store was reported in 245 (67%) of the hypothetical HSB patterns
      and as a first option in 199 (54%). Maternal and/or paternal education had little
      impact on hypothetical HSB. Households with lower SES were more likely to report
      using local grocery stores as a first option and were less likely to use options
      outside the village. The rapid ethnographic survey approach allows for assessment
      of changes in the approach to health care option utilization in cultures
      incorporating new health care paradigms. Public health interventions targeting
      local stores may lead to increased use of ORT, thereby potentially reducing early
      morbidity and mortality due to childhood diarrhea.

PMID- 10075175
TI  - Smoking and deprivation: are there neighbourhood effects?
AB  - Debate has centred on whether the character of places plays an independent role
      in shaping individual smoking behaviour. At the small-area scale, particular
      attention has focused on whether measures of neighbourhood deprivation predict an
      individual's smoking status independent of their own personal characteristics.
      This study applies multilevel modelling techniques to data from the British
      Health and Lifestyle Survey and ward (local neighbourhood) level deprivation
      scores based on four variables from the national Census. Results suggest that
      after taking account of a large range of individual characteristics, both as main
      effects and interactions, together with complex structures of between-individual
      variation, measures of neighbourhood deprivation continue to have an independent
      effect on individual smoking status. In addition, significant between-ward
      differences in smoking behaviour remain which cannot be explained either by
      population composition or ward-level deprivation. The study suggests that the
      character of the local neighbourhood plays a role in shaping smoking behaviour.

PMID- 10075176
TI  - Epidemics and public health in early colonial Somaliland.
AB  - The early colonial period in the Somaliland Protectorate was marked by the
      intrusion of new 'colonial' epidemics and diseases, such as smallpox, cholera,
      influenza, venereal diseases, tuberculosis, relapsing fever and the decline of
      the population. The aetiology of the diseases was social. They were introduced
      into the country through the movement of imperial armies and displaced people,
      the improvement in transportation and the integration of the country into the
      British Empire. The protectorate administration attempted to control the
      epidemics. However, since the medical staff and medical facilities were thin on
      the ground, the effect of the medical campaigns were limited. Not all the medical
      campaigns were a 'mirage', however. Medical campaigns played an important role in
      the control of venereal diseases, particularly syphilis. Overall, the incidence
      of epidemics declined from 1937 onwards. The cause was again social and had very
      little to do with medical campaigns. The ending of the campaigns of conquest, the
      massive movement of armies and people and the development of relative stability
      in the country played a key and decisive role in the decline in the incidence of
      diseases. The aetiology of colonial epidemics and their decline had both socio
      political origins and explanations. The article deals with that neglected aspect
      of the history of Somaliland.

PMID- 10075177
TI  - Medical knowledge and the intractable patient: the case of chronic low back pain.
AB  - Chronic low back pain (CLBP) is endemic in Western societies, and while a good
      deal of attention has been paid to the lay experience of such pain, much less
      sociological attention has been paid to the way in which medical ideas about it
      have been formulated. This paper takes the latter course, tracing the development
      of clinical notions about the relationship between pathological signs and
      expressed symptoms from the 1820's to the 1930's, and then placing these
      developments in the context of postwar notions of 'somatization'. We point to the
      extent to which the disparity between expressed symptoms, pathological signs and
      perceived disability in CLBP has led to the moral character of the sufferer
      forming a constant subtext to medical discourse about the condition. We also note
      the extent to which medical ideas themselves have been constructed in intimate
      linkage with socio-legal questions of compensation and worker's insurance.

PMID- 10075178
TI  - Using conjoint analysis to take account of patient preferences and go beyond
      health outcomes: an application to in vitro fertilisation.
AB  - There has been an assumption in the health economics literature that health
      outcomes are all that need to be considered when attempting to measure the
      benefits from health care interventions. This is most evident in the development
      of the quality adjusted life year (QALY) approach to benefit assessment. This
      paper challenges this view and considers the technique of conjoint analysis (CA)
      as a methodology for both taking account of patient preferences and considering
      attributes beyond health outcomes. The technique is applied to in vitro
      fertilisation. CA is shown to be sensitive to considering health outcomes,
      nonhealth outcomes and process attributes. It is also shown to be internally
      consistent and internally valid. The paper demonstrates the application of CA to
      estimating willingness to pay indirectly. It is argued that benefit assessment
      within health economics should extend beyond health outcomes and future research
      should investigate more thoroughly the potential application of CA in this area.
      However, methodological issues need addressing before the instrument becomes an
      established evaluative instrument.

PMID- 10075179
TI  - HMO physicians' use of referrals.
AB  - Clinical uncertainty is a source of variation in medical decision-making as well
      as a source of work-related stress. Increasing enrollment in organized health
      care systems has intensified interest in understanding referral utilization as
      well as issues such as physician dissatisfaction and burnout. We examined whether
      primary care physicians' affective reactions to uncertainty and their job
      characteristics were associated with use of referrals and burnout. Data came from
      mail surveys of primary care physicians practicing in two large group model
      health maintenance organizations (HMOs) in the USA. Consistent with past
      research, we found that younger physicians had higher referral rates than older
      physicians, and that general internists had higher rates than either family
      practitioners or pediatricians. Greater stress from uncertainty increased
      referrals and referrals were negatively correlated with heavier work demands
      (patient visits per hour). Greater stress from uncertainty, perceived workload
      (too high) and a sense of loss of control over the practice environment were
      associated with higher levels of burnout.

PMID- 10075180
TI  - Personal values of male and female doctors: gender aspects.
AB  - The aim of this study was to elucidate the personal values of physicians. It was
      part of the Physician 93 Study, the purpose of which was to shed light on the
      life situation, career and future plans of young doctors and their views on
      medical education. The survey population included all the medical doctors
      registered during the years 1982-1991 in Finland (N = 4671). In the spring of
      1993 a postal questionnaire was sent to a random sample of 2341 doctors. After
      two reminder letters, 1818 questionnaires (78%) were returned. 59% of the
      respondents were women. Subjects were asked to rate on a 4-point scale each of a
      set of 17 potentially important values listed in the questionnaire, five of which
      were seen by the majority of physicians as very important. These values were:
      family life, health, close friends, success in work or in studies and children's
      success. The potentially important values were conceptualized as indicative of
      eight important dimensions of the values of physicians: close friends, health.
      self actualization, success, universal values, well-being, family and ideology.
      Women doctors rated close friends, health, success, universalism and ideology as
      more important than men doctors.

PMID- 10075181
TI  - Sequential analyses in coercive mother-child interaction: the predictability
      hypothesis in abusive versus nonabusive dyads.
AB  - OBJECTIVE: A two-fold purpose guided the present study: 1) To test the sequential
      relationship between the child's aversive behavior and both the predictability
      and the compliance episodes, as well as the sequential relationship between these
      two mothering episodes proposed by the new predictability hypothesis (Wahler,
      Williams, & Cerezo, 1990); 2) to explore whether or not these patterns are
      specific to these dysfunctional dyads by using a nonabusive comparison group.
      METHOD: Fifty mother-child dyads, 25 abusive and 25 nonabusive, participated in
      this study. Lag sequential analyses were carried out on 302 hours of direct
      observation, 178 hours in the abusive group, and 124 in the nonabusive group.
      RESULTS: Results of the sequential analyses showed that the predictions derived
      from the compliance and predictability hypotheses were supported in both groups.
      The only difference between the groups lies in the new predictability hypothesis,
      so the two mothering reactions are not sequentially related in the nonabusive
      group. CONCLUSIONS: This study revealed interesting findings which suggest that
      these patterns are also found in nonabusive mother-child interactions, but there
      is a qualitative difference between the groups.

PMID- 10075182
TI  - Age and gender differences in children's and adolescents' adaptation to sexual
      abuse.
AB  - OBJECTIVE: How children manifest psychological distress following the discovery
      of sexual abuse requires a better understanding of individual differences in
      developmental capacities and vulnerabilities. This study examined how age at the
      time of the abuse discovery and gender of victim are related to psychological
      distress. METHOD: One hundred and sixty-nine participants (96 children, 73
      adolescents) were interviewed within 8 weeks of discovery of the abuse.
      Multivariate analyses were used to examine how age at discovery, and gender, with
      abuse characteristics as covariates, were related to shame, attribution style,
      depression, self-esteem, and traumatic events sequelae. RESULTS: Adolescents
      compared to children report a higher level of depressive symptoms, negative
      reactions by others, and lower levels of self-esteem, social support, and sexual
      anxiety. Girls compared to boys report higher levels of intrusive thoughts,
      hyperarousal, sexual anxiety, personal vulnerability, and perceiving the world as
      a dangerous place and lower levels of eroticism. CONCLUSIONS: These findings
      suggest the importance of considering individual differences in age and gender
      for understanding patterns of symptom expression. Treatment strategies need to
      reflect these individual differences in adjustment, such as targeting issues of
      sexual anxiety for girls and self-esteem for adolescents.

PMID- 10075183
TI  - Cognitive distortions and blame attribution in sex offenders against adults and
      children.
AB  - OBJECTIVE: Sexual offenders tend to hold attitudes and beliefs which minimize and
      justify their offending behavior. It was hypothesized that distorted thinking
      supporting sexual offending and blame attribution would differ depending on the
      offence characteristics of different groups of sexual offenders. METHOD: Two
      groups of sexual offenders separated on the basis of the age of their victims
      (sex offenders against children, 36; sex offenders against adults, 30) were
      compared on measures of cognitive distortions relating to sex with children and
      rape and a measure of blame attribution which assesses external, mental element,
      and guilt feeling attributions. RESULTS: Child sexual offenders endorsed more
      cognitive distortions relating to sex with children, but there were no group
      differences in cognitive distortions relating to rape. Those who offended against
      adults reported more external attributions and child offenders reported more
      guilt feeling attributions. Mental element attribution related to alcohol
      intoxication and use of violence in the offence, but was not related to group
      differences. CONCLUSIONS: Results are interpreted as suggesting that child sex
      offenders support their offending by more enduring distorted cognitions, while
      those who offend against adults use blame attributions associated with the
      particular offence.

PMID- 10075184
TI  - The long-term impact of childhood sexual abuse in Australian women.
AB  - OBJECTIVE: The aim of this study was to examine the association between childhood
      sexual abuse (CSA) and a range of adverse adult outcomes in a community sample of
      women using multivariate analysis which accounted for a number of potential
      confounding effects. METHOD: Retrospective study of cross-sectional data on the
      long-term impact of CSA, collected as part of a larger two-stage case-control
      study of the possible relationship between CSA and alcohol abuse. Data were
      appropriately weighted to adjust for the different selection probabilities of
      cases and controls. RESULTS: Significant associations were found between
      reporting CSA and experiencing domestic violence, rape, sexual problems, mental
      health problems, low self-esteem, and problems with intimate relationships even
      after taking into account a range of family background factors. Women who had
      experienced abuse involving intercourse were the most vulnerable to these
      negative outcomes. CONCLUSIONS: The findings indicate that the influence of CSA
      on adverse long-term effects is mediated and influenced both by the severity of
      the abuse experiences and by a range of family and social background factors.

PMID- 10075185
TI  - The idealization of women: its role in the minimization of child sexual abuse by
      females.
AB  - OBJECTIVE: The aim was to review the literature on female perpetrated child
      sexual abuse by highlighting how cultural myths about women inhibit recognition
      of this much hidden phenomenon. METHOD: Three sections are presented. Part 1
      evaluates evidence concerning beliefs about child sexual abuse by women which
      minimize the problem. Part 2 provides a theoretical account of psychological
      processes that are hypothesized to maintain these beliefs. Part 3 illustrates
      that professionals working in the area of child sexual abuse are not immune to
      these processes. As a result, recommendations for future professional practices
      are made. RESULT: The paper demonstrates that in the context of what is known
      about child sexual abuse, cultural beliefs which serve to idealize women and
      minimize their potential harm to children are largely invalid. CONCLUSION:
      Individuals are urged to suspend their disbelief about female perpetrated child
      sexual abuse. Denial of the phenomenon may result in it continuing to be under
      reported and trivialized. As this persists the price will ultimately be paid by
      victims of on-going abuse and survivors of past victimization whose suffering
      will be compounded by disparagement of the issue.

PMID- 10075186
TI  - Coping with sexual abuse: development and evaluation of a videotape intervention
      for nonoffending parents.
AB  - OBJECTIVE: The aims of the study were: (1) to develop, apply, and evaluate a
      videotape intervention that targeted the development of supportive behaviors in
      mothers of children who were being examined because of suspected molestation; and
      (2) to examine the relationship between mothers' reported responses to and
      beliefs about the molestation and their children's perceptions of support.
      METHOD: Mothers (N = 87) who had children 4 to 12 years of age were recruited and
      randomly assigned to view either a treatment or control videotape during the time
      when their child was being examined. Observers who were blinded to this
      assignment observed and rated parent-child interactions in the waiting room prior
      to and again after the mothers viewed the videotape. One week after this brief
      intervention, 64 of the mothers and 30 of the children (8- to 12-years-old) were
      interviewed. RESULTS: Mothers who viewed the treatment tape were more likely to
      engage in supportive behaviors with their child immediately after viewing the
      tape, and were able to identify more supportive behaviors at the 1-week followup.
      In addition, mothers' reports of how they responded to the molestation (including
      perceived blame) was related to child perceptions of parental support.
      CONCLUSIONS: The findings indicate that children who have been sexually molested
      are sensitive to the initial reactions of their nonoffending parent to the
      disclosure. In addition, there is some evidence that we can design and deliver
      cost-effective interventions during the early disclosure period that promote more
      positive (or supportive) responses by the nonoffending parent.

PMID- 10075187
TI  - Emotionally abused children presenting to child psychiatry clinics.

PMID- 10075188
TI  - Cognitive behavioral interventions with maltreated children and adolescents.

PMID- 10075189
TI  - The home inventory of dangers and safety precautions-2: addressing critical needs
      for prescriptive assessment devices in child maltreatment and in healthcare.
AB  - OBJECTIVE: This paper describes the development and preliminary validation of a
      prescriptive home danger and safety precaution instrument containing 14
      epidemiological categories to be used in the design and evaluation of family
      tailored injury prevention and safety interventions. METHOD: The HIDSP-2 evolved
      from application and revision of the previous home danger and safety precaution
      recognition and observation instruments. As part of this process, the suitability
      of the HIDSP-2 for use in a broad-based trial was evaluated with 29 low income
      parents exhibiting individual learning needs. Inter-rater reliability and
      stability of scores were examined. Internal consistency was examined for total
      dangers and precautions and for those categories in which there were sufficient
      items to do so. RESULTS: Administrative time was reduced while continuing
      usefulness in the identification and remediation of dangers and implementation of
      precautions was demonstrated. Stability of observation was high. Alphas as a
      measure of internal consistency was satisfactory for total danger and precautions
      separately; however, those for most individual categories were low. There was
      significant reduction in the number of dangers identified initially and
      significant improvement in the safety precautions implemented. CONCLUSIONS: The
      HIDSP-2 can assist healthcare, education, disability, and child protective
      service workers in the development of home safety plans for remediating home
      dangers and implementing precautions. While we see this instrument as eminently
      suitable for use in broad-based interventions and in epidemiological studies,
      further research must continue to examine the psychometric characteristics of the
      individual danger and precaution categories.

PMID- 10075190
TI  - Predicting abuse-prone parental attitudes and discipline practices in a
      nationally representative sample.
AB  - OBJECTIVE: According to sociological and ecological models of abuse, typically
      nonabusive parents could behave abusively towards their children under certain
      circumstances. The purpose of this study was to examine factors that place
      parents at risk of abusing their children by predicting parents' use of
      discipline practices and attitudes that may bias parents towards abusive
      behaviors, which we refer to as abuse-proneness. METHOD: A telephone interview
      was administered by the Gallup Organization to a nationally representative sample
      of 1,000 parents. Using a set of theoretically relevant risk factors, multiple
      regression was used to predict variations in parental attitudes (i.e., attitudes
      towards physical discipline and attitudes that devalue children) and parental
      discipline practices (i.e., physical discipline, nonphysical discipline, and
      verbal abuse). RESULTS: The findings confirmed the importance of examining
      elements of parental attitudes, history, personality characteristics, as well as
      religion and ideology in predicting abuse proneness. Child age also was an
      important predictor in all analyses except predicting parental attitudes that
      devalue children. The findings suggest also, however, that it may be unduly
      simplified to regard parents as somewhere on a continuum of nonpunitive to
      punitive disciplinarians. Social isolation was not a significant predictor in any
      of the analyses. CONCLUSIONS: Although many important theoretical predictors of
      abuse proneness were confirmed, many questions arise regarding the diversity of
      discipline practices that parents use, and the relevance of child's age and
      social isolation in predicting abuse proneness. Implications for practitioners
      and future research are discussed.

PMID- 10075191
TI  - The efficacy of group treatment for survivors of childhood abuse.
AB  - OBJECTIVE: To assess the effectiveness of a new model of group treatment for
      sexual abuse survivors over individual therapy alone. METHOD: In this quasi
      experimental design, 32 women were in either group treatment (N = 22) or a wait
      list comparison group (N = 10). They completed standardized measures on
      depression, self-esteem, and trauma symptomatology at pretest and after
      completing the 10 to 12 week group. All were in concurrent individual therapy.
      RESULTS: On average, both groups of women decreased depression and trauma
      symptoms as well as increased self-esteem. However, the clients in the treatment
      group improved their depression and anxiety to a statistically significantly
      greater degree than clients in the wait-list comparison condition. Improvement
      approaching statistical significance was found in levels of self-esteem in the
      treatment as compared to the wait-list condition. CONCLUSION: The group
      intervention was significantly more effective than individual treatment alone on
      depression and anxiety. The inclusion of the wait-list comparison group was
      critical in interpreting the improvement noted by all of the women in treatment.

PMID- 10075192
TI  - The prevalence and circumstances of child sexual abuse: changes across a decade.
AB  - OBJECTIVE: This study reports the prevalence of child sexual abuse of African
      American and European American women and compares the circumstances of these
      incidents to data collected a decade ago. METHOD: Stratified probability sampling
      was used to recruit comparable samples of African American and European American
      women in Los Angeles County for a larger study of women's sexual decision making.
      Incidents of contact abuse were obtained from women 18 to 36 years old in 1994
      and compared to women with those demographic characteristics from a comparable
      1984 dataset. The prevalence of abuse, characteristics of the victim, assault,
      alleged perpetrator, disclosure, and long-term effects by ethnic group
      affiliation were assessed. RESULTS: Of the total sample, 34% reported at least
      one incident prior to age 18. Ethnic differences were found with respect to
      prevalence, location of abuse, and number of incidents of rape. While comparisons
      made with the 1984 dataset revealed no significant difference in prevalence rates
      over the 10 year period, changes in circumstances were noted. CONCLUSIONS:
      Although the prevalence of child sexual abuse in Los Angeles County remained
      fairly stable, several circumstances of abuse underwent change. These
      characteristics are discussed in relation to how sexual abuse among ethnically
      diverse samples in Los Angeles County has changed over a decade and how these
      differences can help better tailor prevention messages to different communities.

PMID- 10075193
TI  - A new measure for distress during child sexual abuse examinations: the genital
      examination distress scale.
AB  - OBJECTIVE: The primary aim was to develop a simple scale to quantify indices of
      emotional distress during the rectal-genital (anogenital) phase of a child sexual
      abuse examination. METHOD: A scale successfully developed to measure reactions of
      children to painful procedures, in particular bone marrow aspirations, was used
      as a model (Elliot, Jay, & Woody, 1987). This new scale was developed to have a
      simplified rating format, more relevant operational definitions and possibly a
      different set of behavioral categories. This new scale was developed using 300
      children being examined for possible child sexual abuse. Intraclass correlation
      coefficients identified reliable items to use. Factor analysis and Cronbach alpha
      were employed to understand the internal structure of the scale. Paired t-tests,
      Pearson correlations and hierarchical regression were used to explore validity.
      RESULTS: A simple 7-item scale was developed along with two subscales
      representing agitated and verbally mediated distress. Ratings of distress were
      significantly greater during the anogenital phase than the general physical part
      of the examination. Increased distress was associated with positive physical
      findings. Ratings by the children that they disliked the physician looking at
      their bodies provided discriminant validity by correlating with increased scores
      for emotional distress during the anogenital segment of the examination.
      CONCLUSION: The Genital Examination Distress Scale (GEDS) has been developed for
      measuring the emotional distress of children during the anogenital component of
      child sexual abuse examinations. The GEDS has been provided for prudent use.
      Descriptive data offer a comparative standard for other programs and research.

PMID- 10075194
TI  - Sibling incest: a Hong Kong experience.
AB  - OBJECTIVE: The one case study intends to gain a preliminary understanding of the
      long term impact of older brother-younger sister incest in Hong Kong RESULTS: The
      adult survivor's experience did cohere with Western studies to date on age of
      onset, symptomatology, and feelings such as shame and guilt. The symptoms and
      negative feelings might also be the results of inaccessible parents and negative
      parental response at disclosure. Specific contextual factors such as patriarchal
      power structure, strong moral codes, and secrecy of family shame in Chinese
      culture may have contributed to the victim's inability to protect herself from
      her older brother's sexual advances. CONCLUSION: This case study calls for a
      multi-dimensional, and interactive rather than a unidimensional and
      unidirectional view to explore into the individual, familial, and contextual
      factors that may contribute to sibling incest and a delay in disclosure. The
      brief analysis is also a plea for systematic research in the Hong Kong context
      and comparative studies that take into account cultural specificity.

PMID- 10075195
TI  - Pregnancy and delivery for women with a history of child sexual abuse.
AB  - OBJECTIVE: To study whether women with a history of child sexual abuse are at
      increased risk of delivering low birth weight infants. Secondary aims were to
      study smoking habits, obstetric complications, health care use, and health
      complaints during pregnancy among women with a history of child sexual abuse.
      METHOD: In a case control study, 82 women with birth of a low birth weight infant
      (< 2500 g) (cases) and 91 women with birth of a normal birth weight infant
      (controls) were interviewed about experiences of child sexual abuse. RESULTS:
      Fourteen percent of the women disclosed a history of child sexual abuse involving
      at least genital touch. Birth of a low birth weight infant was not associated
      with a history of child sexual abuse (OR 1.03, 95% CI .44-2.40). More women with
      a history of child sexual abuse were smokers during pregnancy (56% vs. 31%)
      compared with nonabused women. Abused women reported lower age at menarche and
      sexual debut. Nonscheduled contacts with the antenatal care clinic and discomfort
      during pregnancy were more frequent among abused women when controlled for low
      birth weight. CONCLUSIONS: Women who delivered low birth weight infants were not
      more likely to have experienced child sexual abuse than women who delivered
      nonlow birth weight infants. Abused women were unemployed and daily smokers more
      often than nonabused women. Some of the abused women reported more health
      complaints, and more use of health care services during pregnancy, but did not
      have more obstetric complications during pregnancy and delivery.

PMID- 10075196
TI  - Assessing the accuracy of a child's account of sexual abuse: a case study.
AB  - OBJECTIVE: The objective of the case study reported in this paper was to examine
      the accuracy of one child's account of a sexually abusive incident. The
      availability of an audio recording of the last in a series of abusive incidents
      enabled us to assess accuracy in greater detail than has hitherto been possible
      in forensic contexts. METHODS: Information given by the victim during an
      investigative interview was compared with an audio-taped record of the incident.
      Content analyses of the interview involved quantitative and qualitative analyses
      of the victim's account, and a qualitative analysis of the eliciting utterances.
      A CBCA analysis was performed on the victim's account to assess its purported
      credibility. RESULTS: Over 50% of the informative details reported by the victim
      were corroborated by the audio-recorded account (of which 98% were central, i.e.,
      allegation related and 64% were confirmed by more than one source (audio
      recording, suspect, witness). A total of 10 CBCA criteria were present in the
      victim's free-narrative account of the last abusive incident. CONCLUSIONS: Our
      findings confirm that children can indeed provide remarkably detailed and
      accurate accounts of their experiences.

PMID- 10075197
TI  - Ocular inflammation models by topical application: croton-oil induced uveitis.
AB  - PURPOSE: The aim of the present investigation was to develop a new ocular
      inflammation model in the rabbit by comparison of the inflammation response
      induced by the topical application of several irritating agents (carrageenan,
      Freund's adjuvant, alkali and croton oil). METHODS: The following parameters were
      determined after the application of each irritant to the eyes of female, white,
      New Zealand rabbits: Corneal edema and the Tyndall effect (slit-lamp
      biomicroscopy), corneal thickness (biometer-pachometer) and aqueous humor levels
      of the prostaglandin E2 (R.I.A), total protein (Weichselbaum technique), albumin,
      albumin/globulin (Doumas technique) and leukocytes (coulter counter). RESULTS:
      Croton oil 1-4% (40 microl) produced edema and a Tyndall which showed a
      proportional increase with croton oil concentration. Ultrasonic pachometer
      measurement of the variation in corneal thickness (3-168 h) showed a dose
      dependent response (p<0.01) from the 8th to the 168th hour. Uveitis and
      considerable increases in the levels of the prostaglandin E2 (4.50+/-0.40 pg/0.1
      ml vs. 260.03+/-2.03 pg/0.1 ml), total protein (0.25+/-0.05 g/l vs. 2.10+/-0.08
      g/l), albumin, albumin/globulin and leukocytes were observed in the aqueous humor
      24 h after topical application of croton oil 3% (40 microl). All the values
      obtained were statistically significant (p<0.01). CONCLUSIONS: The topical
      application of 3% croton oil (40 microl) was most appropriate for the evaluation
      of the inflammatory process in the anterior chamber and for the determination of
      the effects of intraocular penetration. The inflammatory mechanism in this model
      is thought to involve the activation of the arachidonic acid pathway accompanied
      by the breakdown of the blood-aqueous barrier permitting high molecular weight
      proteins to enter the aqueous humor. Typology: anterior uveitis with corneal
      edema.

PMID- 10075198
TI  - The spatial organization of apical junctional complex-associated proteins in
      feline and human corneal endothelium.
AB  - PURPOSE: Previous studies suggest that proteins associated with the apical
      junctional complex (AJC) play essential roles in the development, maintenance and
      regulation of barrier function in transport epithelium and vascular endothelium.
      The goal of this study is to identify and determine the spatial organization of
      several major AJC-associated proteins in normal human and feline corneal
      endothelium. METHODS: Fresh corneal tissue was obtained from 4 recipient buttons
      removed during penetrating keratoplasty (two from keratoconus patients, and two
      from patients with post-traumatic stromal scarring) as well as from 16 cat eyes.
      En bloc double- and triple-labeling of corneas was performed using phalloidin,
      and mouse, rat or rabbit antibodies to ZO-1, occludin, pan-cadherin, alpha
      catenin, beta-catenin and plakoglobin (gamma-catenin). The 3-D localization of
      the proteins was then determined in situ using laser confocal microscopy.
      RESULTS: Similar staining patterns were obtained for the corneal endothelium of
      normal cat corneas and fresh human buttons. Apically, f-actin was arranged into
      dense peripheral bands (DPB) in individual cells that were separated from those
      in adjacent cells. Diffuse phalloidin staining also extended from the DPB into
      the cytoplasm apically. Although weaker, phalloidin staining also appeared to be
      associated with the basolateral cell borders. The adherens junction protein,
      cadherin, formed a thin pericellular band at the apical cell junctions between
      the DPB. In addition, cadherin staining also appeared to extend along the
      basolateral cell borders in a convoluted pattern. Staining for alpha-catenin,
      beta-catenin and plakoglobin each showed a nearly identical organization as
      cadherin. ZO-1 formed a single apical band that was localized between the DPB;
      however, no basolateral ZO-1 staining was detected. Interestingly, the
      distribution of ZO-1 was discontinuous around the cell, with the largest gaps
      occurring at the Y-junctions between adjacent endothelial cells. Positive
      staining for occludin was not detected in either human or feline corneal
      endothelium. CONCLUSIONS: The composition and organization of the AJC of corneal
      endothelium appears to be different from that of classical transport epithelia;
      these findings may be related to functional differences between these two cell
      types.

PMID- 10075199
TI  - Diltiazem reduces retinal neovascularization in a mouse model of oxygen induced
      retinopathy.
AB  - PURPOSE: To assess the effect of diltiazem, a calcium channel blocking agent, on
      oxygen induced retinopathy (OIR) in a mouse model using neovascular nuclei
      quantitation and a quantitative scoring system based on examining fluorescein
      perfused retinal whole mount preparations. METHODS: The mouse model of oxygen
      induced retinopathy consisting of a 5 day exposure to 75% oxygen from postnatal
      day 7 to 12 was used to produce retinal neovascularization. Fluorescein
      conjugated dextran angiography of retinal vasculature was performed and retinal
      whole mounts were prepared to score features of retinopathy. The parameters that
      were scored in a masked fashion included blood vessel growth, blood vessel tuft
      formation, extra retinal neovascularization, degree of central vasoconstriction,
      retinal hemorrhage, and tortuosity of vessels. Diltiazem (0.05-0.5 mg/kg/day
      subcutaneously for five days) was administered to mice pups during exposure to
      oxygen to determine if calcium channel blockade altered retinopathy. In addition,
      quantification of retinal neovascular nuclei was performed in a masked fashion
      with periodic acid Schiff (PAS) staining of frozen eye sections. RESULTS: Animals
      that were exposed to hyperoxia for five days had a median (25th, 75th quartile)
      retinopathy score of 9 (8,11) versus control animals that had a retinopathy score
      of 1 (0,1) with p<0.001. Subscores for blood vessel growth, blood vessel tufts,
      extra-retinal neovascularization, central vasoconstriction, hemorrhage, and blood
      vessel tortuosity were all significantly different between control and treated
      animals. In addition, quantification of neovascular nuclei showed a significant
      increase in the number of nuclei extending beyond the inner limiting membrane
      into the vitreous in hyperoxic treated animals. Diltiazem at doses of 0.2 and 0.5
      mg/kg/day improved the retinopathy as measured by the total retinopathy score [5
      (4,6) and 4 (3.75,5.25), respectively]. The average number of extraretinal
      neovascular nuclei per retinal section (mean +/-standard deviation) was
      significantly decreased by diltiazem at doses of 0.2 and 0.5 mg/kg/day (31.4+/
      18.8 and 20.9+/-6.9, respectively) when compared to hyperoxic treated animals
      (56.1+/-21.5). CONCLUSIONS: Diltiazem reduces oxygen induced retinopathy in the
      mouse as measured by a scoring system based on a retinal whole mount method of
      retinal neovascularization and by quantification of extra retinal neovascular
      nuclei.

PMID- 10075200
TI  - The lack of extracellular laminin beta2 chain deposition correlates to the loss
      of conjunctival epithelial keratin K4 localization in culture.
AB  - PURPOSE: To examine the effects of external modulation of epithelial-mesenchymal
      interaction on conjunctival epithelial cell differentiation characteristics.
      METHODS: Keratin K4 and laminin beta2 chain protein localization was examined in
      an organotypic model which facilitates the comparison of differentiation
      characteristics of conjunctival epithelium interacting with conjunctival basement
      membrane or corneal basement membrane. In addition, keratin K4 and laminin beta2
      chain localization was examined in primary cultures of conjunctival epithelial
      cells and fibroblasts. The synthesis and secretion of laminin beta2 chain by
      conjunctival fibroblasts in culture was determined by western blot analysis and
      immunoprecipitation. The ability of conjunctival epithelium to respond to
      exogenous laminin beta2 chain was assayed by culturing epithelial cells on a
      laminin matrix isolated from human placenta. RESULTS: In culture, conjunctival
      fibroblasts synthesize and secrete laminin beta2 chain but do not deposit this
      chain into an extracellular matrix substrate or basement membrane-like structure.
      The lack of extracellular deposition of this chain correlates to the gradual loss
      of keratin K4 protein in conjunctival epithelial cell culture. Conjunctival
      epithelium remains responsive to laminin beta2 chain in vitro because keratin K4
      localization can be rescued in these cells by culture on a substrate of exogenous
      placental laminin. CONCLUSIONS: In vitro, alterations in native conjunctival
      epithelial-mesenchymal interactions results in aberrant basement membrane laminin
      isoform composition. This, in turn, leads to the loss of adult epithelial cell
      phenotype characteristics, suggesting that at least some aspects of conjunctival
      epithelial cell differentiation are regulated by the extracellular matrix.

PMID- 10075201
TI  - Immunohistochemical localization of dopamine-beta-hydroxylase in human and monkey
      eyes.
AB  - PURPOSE: To investigate the pattern of dopamine-beta-hydroxylase (DBH)-containing
      fibers in human and monkey eyes. METHODS: DBH-containing fibers were detected by
      immunohistochemistry. The primary antibody used recognized DBH, the key enzyme in
      the conversion of dopamine to noradrenaline. RESULTS: In the anterior segment,
      DBH immunoreaction product was found in the peripheral corneal endothelium layer,
      in both the dilator and sphincter muscles of the iris, as well as in the anterior
      border layer of the iris. The ciliary muscle and the stroma of the ciliary
      processes were also zones of concentration. In the posterior segment, staining
      was seen around blood vessels in the choroid, in the vascular walls of the short
      posterior ciliary arteries and in the ciliary nerves. The retina was also
      immunopositive, with specific labeling in cones and rods of photoreceptors, inner
      and outer plexiform layers and ganglion cell layer. There was no significant
      difference in the distribution of DBH-related immunoreactivity in human and
      monkey eyes. CONCLUSIONS: The localization of DBH-related immunoreactivity is
      generally consistent with the known physiological roles of noradrenaline.
      However, an apparently high concentration of the enzyme in the anterior border
      layer of the iris and in retinal photoreceptors raises questions about the
      possible role of DBH-containing fibers in these structures.

PMID- 10075202
TI  - Quantifying leukocyte dynamics and plugging in retinal microcirculation of
      streptozotosin-induced diabetic rats.
AB  - PURPOSE: To determine leukocyte kinetics in the retinal microcirculation of
      streptozotosin-induced diabetic rats. METHODS: Rats were made diabetic with
      intraperitoneal injection of streptozotosin. For one month after injection, the
      alteration of the velocity and plugging of leukocytes were investigated using
      acridine orange, which stains leukocytes, and scanning laser ophthalmoscopy.
      Blood plasma protein levels, such as fibrinogen and alpha1- and alpha2- globulin,
      were also measured. RESULTS: Throughout the observational period, mean leukocyte
      velocity was similar between diabetic (1.53+/-0.45 mm/sec) and age-matched
      control (1.58+/-0.23 mm/sec) rats, but the coefficient of variation of the
      velocity in the diabetic rats was twice as large as that in the control rats.
      Plugging was increased in a sigmoidal fashion and saturated for 5 weeks or later.
      No differences were seen in plasma protein levels between groups. CONCLUSIONS:
      Within one month of the hyperglycemic condition, the velocities of leukocytes in
      capillaries were more varied and the leukocytes were plugged time-dependently.
      This action occurred not because the blood fibrinogen and globulin levels were
      altered, but because of the leukocyte-endothelium interaction. In streptozotosin
      induced diabetic rats, retinopathy usually cannot be found during the fundus
      examination and fluorescein angiography. In the level of the microcirculation,
      however, some of the disorders have already occurred.

PMID- 10075203
TI  - Membrane lipid alpha-crystallin interaction and membrane Ca2+ -ATPase activities.
AB  - PURPOSE: To determine the effect of alpha-crystallin binding on lens membrane
      lipid characteristics and the stability of Ca2+ -ATPase activity when challenged
      with H2O2 or elevated temperatures. METHODS: Alpha-Crystallin binding to muscle
      sarcoplasmic reticulum membranes was quantified using a centrifugation protocol.
      Alpha-Crystallin binding to lens epithelial lipids was measured by a fluorescence
      energy transfer technique. Lipid phase transition temperature and lipid order was
      measured using fluorescence spectroscopy. Ca2+ -ATPase activity was measured
      using classical biochemical assays. RESULTS: The main phase transition
      temperatures of multilamellar vesicles composed of sphingomyelin or lipids
      extracted from bovine lens were 40 degrees C and 20 degrees C, respectively. In
      the presence of saturating amounts of alpha-crystallin, the phase transition
      temperature and lipid order of both sphingomyelin and lens lipid membranes
      remained almost the same as that without alpha-crystallin. The interaction of
      alpha-crystallin and lipid is likely to be restricted to the membrane surface.
      The binding of alpha-crystallin did not influence the oxidative or thermal
      inactivation of the Ca2+ -ATPase pump. CONCLUSION: Alpha-Crystallin-lens membrane
      binding does not protect the Ca2+ -ATPase pump from thermal derangement or
      oxidation by H2O2.

PMID- 10075204
TI  - TGF-beta elicits fibronectin secretion and proliferation in cultured chick lens
      epithelial cells.
AB  - PURPOSE: To determine if the cataract forming influence of TGF-beta on lens cells
      is due to its effects on the ECM. METHODS: Primary cultures of chick lens annular
      pad cells were exposed to TGF-beta and various exogenously supplied components of
      the lens capsule. Proliferative response were measured through tritiated
      thymidine incorporation into DNA. Cell spreading accompanying increased matrix
      interactions and growth was monitored with phase contrast microscopy. ECM
      proteins were detected in culture media and as deposited matrices with Western
      blotting and silver staining. TGF-beta receptors were identified with Western
      blotting. RESULTS: Chick lens cells were shown to express type I and II TGF-beta
      receptors. TGF-beta stimulated cell growth and ECM production particularly with
      regard to fibronectin. Fibronectin was secreted into the culture medium and
      deposited onto plastic substrates. Plating cells on ECM components found in the
      lens capsule further increased their growth in response to TGF-beta. CONCLUSIONS:
      These results indicate that TGF-beta may have a normal function in the lens
      regulating capsular protein production. The potent stimulation of lens cell
      growth by TGF-beta may be due to mis-regulated production of lens capsular
      proteins not normally found in great abundance.

PMID- 10075205
TI  - Social, cultural and technological determinants of maternal and neonatal health.

PMID- 10075206
TI  - IAMANEH and the new concept of reproductive health. International Association for
      Maternal and Neonatal Health.
AB  - Prof. Hubbert De Watteville, first Secretary General and founder of the
      International Federation of Gynecologists and Obstetricians (FIGO), created the
      International Association for Maternal and Neonatal Health (IAMANEH) in 1977,
      after realizing that the improvements in maternal and neonatal health observed in
      developed countries were not benefiting the so-called Third World. The purpose of
      IAMANEH was to stimulate local associations to take initiatives to improve the
      health of the women and their children. Lack of attention to women's own health
      has been characteristic of the emphasis on antenatal care to protect the newborn
      or family planning to reduce demographic growth, with little attention to the
      needs of women themselves. The evolution to the more comprehensive concepts of
      reproductive health has been slow and moved by a few visionaries in the
      Obstetrics and Gynecology establishment and by the women's rights movement.
      Currently, the concept has been accepted at world conferences, such as those of
      Cairo (1994) and Beijing (1995). Brazil officially incorporated an even wider
      concept of Comprehensive Women's Health Care, originated at the State University
      of Campinas and formally adopted by the Federal Government in 1984. It was placed
      in practice in the state of Sao Paulo between 1987 and 1990, showing important
      improvements in the quantity and quality of services provided to women.

PMID- 10075207
TI  - Understanding sexual and reproductive violence: an overview.
AB  - International agreements recognizing different forms of violence as violations of
      human rights and the definition provided by the 1993 UN Declaration on the
      Elimination of Violence against Women are taken as a starting point and its
      implications analyzed, emphasizing gender roles and stereotypes. Violence against
      women is related to violence in general, to the so-called culture of violence.
      Factors influencing a culture of violence are discussed, as well as the
      differences between public and private violence, emphasizing the need to
      understand their interaction to be effective in preventing violence against
      women. It is concluded that all violence stems from unbalanced exercise of power,
      creating injustice and lack of real democratic interaction. When left
      unchallenged such situations become part of the culture of individuals and
      societies, reinforcing the use of violence to solve conflicts. Hence, preventing
      violence against women requires cultural, social, economic, and political changes
      that are only possible by mobilizing society as a whole.

PMID- 10075208
TI  - Maternal mortality due to violence.
AB  - The objectives were to investigate the death of women by violent injuries,
      including induced abortion, in the Province of Cordoba, Argentina, 1992-1996 and
      to perform a bibliographic review on maternal death due to violence. Reports of
      autopsies of all violent deaths in women aged 12-44 years were reviewed to
      determine the cause of death for cases of suicide, homicide, accident or induced
      abortion and a bibliographic review was performed through MEDLINE. Two hundred
      and seventy two women died due to violence, including 22 which were due to
      complications of induced abortion. The remaining 250 deaths were: 44 (17.6%) by
      suicide, 51 (20.4%) by homicide and 155 (62%) by traffic accidents, including 6
      pregnant women (2 died by suicide, 1 by homicide and 3 by accidents). Violence
      against women and pregnant women is a growing problem in developing countries.
      The implication of a simplified screening has been proposed to identify abuses
      against women, searching for frequency of abuse, its severity and to determine
      who provokes it.

PMID- 10075209
TI  - Domestic violence and substance abuse.
AB  - The females and children have been the victims of family violence in most
      societies and cultures. The use of tobacco, alcohol and narcotic drugs are
      responsible in aggravating the violence. Incidences of domestic violence is
      significantly higher in substance abusers than others. It is equally present in
      countries where the status of women is high. Education level and economic status
      does not affect the incidence of domestic violence. Therefore we must look at
      other factors which perpetuate domestic violence. It is time for governments,
      societies and thinking people to give serious thought on how to reduce domestic
      violence and bring sanity into the community. Tobacco, alcohol and narcotic drugs
      are well on their way to the 'road of destruction' and fragmentation of social
      fabric. The conscience of the world needs to be roused to prevent the march of
      substance abuse. In the words of the Nobel laureate poet Tagore, I must say,
      'into that heaven of freedom my father, let my country awake'.

PMID- 10075210
TI  - Gender violence and reproductive health.
AB  - The available literature reflects the growing interest in gender violence and
      reproductive health. Violence is generally studied by identifying pathologies,
      measuring their demands on services and evaluating their repercussions on fetal
      outcome. Institutional violence, however, has received little attention and is
      mainly concerned with the consequences of inappropriate use of technologies. Data
      from the Sexuality and Health Feminist Collective shows that among patients,
      20.5% stated that they have never talked about their sexual life with their
      partners; 38.3% stated that they have had sexual intercourse against their will,
      including situations ranging from sexual harassment to rape which was referred by
      12.3% of them. One of the most relevant issues arising from the anamnesis and
      interviews of these women was the violence to which they were submitted by health
      services. The high prevalence of violent situations indicates the urgency of
      incorporating an approach which deals with gender violence and promotes the
      empowerment of women into the routine of reproductive health services.

PMID- 10075211
TI  - The traditional birth attendant: a reality and a challenge.
AB  - The traditional birth attendant (TBA) is an institution as old as the birthing
      process in the human species. Generally a female, in the absence of a better
      alternative, continues to deliver two thirds of the world's babies. A number of
      studies generated international interest in training TBAs. A review of TBA
      training and utilization programs in more than 70 countries over the past three
      decades revealed that there are very limited examples of their successful
      utilization. If unsupervised the TBA tends to slide back into her old ways and if
      unsupported she is rendered helpless when a killer strikes during child birth.
      The impact of trained TBAs on maternal mortality ratios is not palpable because
      of other factors such as accessibility of essential obstetric services. The
      challenge for the policy makers is to make the best use of this available human
      resource but simultaneously plan and implement a definite replacement strategy.

PMID- 10075212
TI  - Traditional birth attendants and their practices in the State of Pernambuco rural
      area, Brazil, 1996.
AB  - OBJECTIVE: To obtain socioeconomic information about TBAs in the State of
      Pernambuco and information concerning their practices. METHOD: Statistical
      analysis of the answers to structured questionnaires applied to 127 TBAs.
      RESULTS: The results of a survey with 127 TBAs conducted in the rural area of the
      State of Pernambuco (Brazil) is presented in this paper. TBAs in rural Pernambuco
      are a group of basically old and very poor and uneducated women. Most of them
      learned to attend births by themselves or by helping another TBA. Thirty percent
      learned midwifery in hospital delivery rooms, helping doctors and nurses. How the
      TBAs learned to help births seemed to be the most influential factor on the kind
      of practices they use. TBAs who learned from other TBAs from the community seem
      to have the least interventionist approach, followed by the TBAs who learned by
      themselves. They are more likely to perform more home births and avoid practices
      such as shaving the pubic hair, vaginal exams, artificial rupture of the
      membranes, episiotomy and early cord clamping. CONCLUSION: The way women learned
      midwifery is the most important determinant of their practice.

PMID- 10075213
TI  - The midwife and her functions by level of care.
AB  - The role the midwives play in women's healthcare in Chile demonstrates
      appropriate utilization of human resources according to their capacity to provide
      services. Historically, the Chilean midwife came into being more than 160 years
      ago, exclusively as a birth attendant. The midwives' functions have evolved,
      particularly during the last few decades, following the demographic and
      epidemiological evolution of the Chilean population and the new paradigm of
      healthcare addressed to woman throughout her life cycle, not only during
      pregnancy and childbirth. At the present time, the midwife is the professional
      that provides the great majority of gynecological and obstetrics care at the
      primary healthcare level, while also attending most of the deliveries in the
      public health services. The close link with physicians working as a team, and the
      emotional ties of the midwife as a provider with the woman as a client, is
      emphasized as an additional advantage of the presence of the midwife as a key
      person in women's healthcare.

PMID- 10075214
TI  - Influence of the position of the mother at delivery over some maternal and
      neonatal outcomes.
AB  - OBJECTIVE: Evaluate possible advantages or disadvantages of the sitting over the
      horizontal position during the second stage of labor. DESIGN AND METHODS:
      Clinical trial randomly selecting 127 volunteers for the sitting position and 121
      for the horizontal position during the second stage of labor. Duration of the
      second stage and of expulsion of the placenta, vulvo vaginal and perineal
      lacerations, blood lost and Apgar score were evaluated. RESULTS: There was a non
      significant decrease of 3.4 min in the duration of the second period in the
      vertical position in comparison with the horizontal position. There was a similar
      difference in the duration of delivery of the placenta, but also non-significant.
      Blood loss was slightly greater among women delivering in vertical position, but
      the difference did not reach significance. Breastfeeding did not show any
      influence on blood loss and on the time for delivering the placenta. The
      incidence of perineal trauma was 44.1% for vertical position and 47% for
      horizontal position in the whole group and of 47.8% and 71.2% in the group with
      history of episiotomy. This last difference was statistically significant. The
      results of this study are in the line of other studies that suggest some
      advantages and possible disadvantages of the vertical position. CONCLUSIONS:
      Mothers should be given the choice of the posture to be assumed during
      parturition. The supine position should not be imposed and episiotomy should not
      be a routine.

PMID- 10075215
TI  - Evaluating technologies in reproductive health: case studies of a consumer
      protection approach.
AB  - OBJECTIVE: A consumer-protection assessment and action program aimed at improving
      reproductive health technologies is reviewed. METHODS: Evaluations employed both
      literature review, synthesis, market analysis and laboratory testing for
      conformity to standards of a wide range of products which affect reproductive
      health on the Brazilian market 1995-1997. Anti-infective gynecological products,
      ampicillins, condoms, pregnancy tests, hormonal contraceptives, infant formulas,
      selected teratogens, bromocriptine and prostaglandins were studied. Actions
      include dissemination in periodicals and the mass media, consumer education,
      pressure for regulation, negotiations with manufacturers and legal action.
      RESULTS: The program was effective in improving the supply and regulation of
      some, but not all products studied. Impact on health and utilization are unknown.
      CONCLUSION: A significant proportion of products studied are unsafe, ineffective
      or of sub-standard quality. A combination of careful scientific work, strong
      links between scientists and social movements, dissemination and legal action,
      can effectively improve the quality of products which affect reproductive health.

PMID- 10075216
TI  - Contraceptive technology and family planning services.
AB  - A large variety of modern contraceptives is now available, including several
      means to administer hormonal contraception, highly effective long-term methods
      and simple sterilization techniques. Methods under research include immuno
      contraceptives for women and men, hormonal methods for men, new approaches to
      female hormonal contraception and improved barrier methods. Modern contraceptives
      are effective and safe for most women, and some methods have beneficial health
      effects other than prevention of pregnancy. However, underlying health conditions
      may decrease the safety of a given method. The appropriate use of the technology
      available requires screening for biomedical conditions and counseling that
      enables the selection of methods according to the life style of women and
      couples. Contraceptive methods have had a considerable positive impact on
      maternal and infant health and on population growth, but unwanted pregnancies and
      unsafe abortion still occur in large numbers. This shows the need to improve
      access to and quality of family planning services including the availability of
      contraceptives, sensitive providers trained in technical matters and
      communication skills, and communication between the community, the providers and
      the managers.

PMID- 10075217
TI  - Appropriate technology: antenatal care.
AB  - Appropriate health technology should be effective, safe and feasible. The current
      antenatal care model originated from western countries. The absence of direct
      randomized, controlled trials precludes a straight forward evaluation of the
      impact of prenatal care on birth outcomes. Interventions of proven benefits in
      eliminating or alleviating adverse maternal outcomes include routine iron and
      folate supplementation in areas of high anemia prevalence, hemoglobin
      determination late in pregnancy, screening for asymptomatic bacteriuria by urine
      culture or dipstick, serologic screening and treatment of syphilis, obtaining a
      history of difficult labor in multipara or height in nullipara and external
      cephalic version at term. Interventions of proven benefits in eliminating or
      alleviating adverse newborn outcomes include routine measurement of fundal
      height, reduction of maternal physical strain, diagnosis and treatment of
      tuberculosis, malaria prophylaxis, adequate tetanus immunization, antenatal and
      perinatal Zidovudine in HIV-positive mothers and one vaginal examination during
      pregnancy. Only these interventions of proven benefits should be implemented.

PMID- 10075218
TI  - Evidence-based intrapartum care: evidence from the Cochrane library.
AB  - OBJECTIVE: To describe the concepts on which systematic reviews of randomized
      controlled trials are based, and to explore the evidence for effectiveness of
      clinical interventions during labor and delivery. METHODS: Review of systematic
      reviews of interventions during labor and delivery, published in the Cochrane
      Library. RESULTS: Some commonly applied clinical interventions are supported by
      evidence; others are not. CONCLUSION: It is possible to classify interventions
      during labor and delivery according to their effectiveness, to improve clinical
      care, identify priorities where resources are scarce, and help set clinical
      research agendas.

PMID- 10075219
TI  - Safe motherhood: the message from Colombo.

PMID- 10075220
TI  - Advances in perinatal medical care--from our experience.
AB  - In the last 30 years, maternal and perinatal mortality rates have markedly
      improved in Japan. These results are supported by the advanced technologies and
      newly developed treatments in obstetric and neonatal medicine, the evidence of
      which will be described through the authors' experiences. Ultrasound-guided
      treatments for fetuses and pediatric surgery for extremely tiny infants have been
      performed with cooperation among cardiac surgeons, anesthesiologists and
      perinatologists. The remarkable achievements in neonatal medicine are surfactant
      replacement therapy, application of high frequency oscillation (HFO) respirator,
      nitric oxide and extracorporeal membrane oxygenation (ECMO) systems and
      transcutaneous blood gas monitoring. The possibility to have a safe pregnancy and
      delivery arose for women with severe medical complications such as diabetes
      mellitus (DM), heart diseases, and hemo-dialysis, factors formerly regarded as
      contraindications to pregnancy. The accumulative data of these high-risk
      pregnancies treated in our center are introduced. It is noted that molecular
      mechanisms in fetal growth have been elucidated to some extent. The insulin-like
      growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP1) system, and cytokines,
      are involved in the fetal growth. Newly developed treatments such as urinary
      trypsin inhibitor (Urinastatin) for prevention of preterm delivery and
      amnioinfusion to cases of preterm premature rupture of the membrane are
      summarized. Finally, the reference to advanced medicine and its side effects lead
      to broad discussions regarding the future development of perinatal medicine.

PMID- 10075221
TI  - Abortion and maternal health.
AB  - Since the beginning of recorded history, women have attempted to terminate
      unwanted pregnancies. Despite the safety of modern techniques of abortion, many
      women throughout the world still have to resort to unsafe abortions, placing
      themselves at considerable risk. The World Health Organization estimates that
      there are approximately 20 million unsafe abortions performed each year, and
      estimates of maternal deaths as a result of abortion range between 60,000 and
      100,000 per year. With free and legal access to safe abortions, rates of
      complications and mortality drop dramatically. There is an urgent need for
      efforts to prevent unwanted pregnancies in order to reduce the need for abortion;
      for the early identification of abortion complications and easy access to
      treatment for women suffering those complications; for expansion of safe abortion
      availability; and for proper training and resources for providers of abortion
      services.

PMID- 10075222
TI  - The influence of abortion legislation on maternal mortality.
AB  - Worldwide some 20 million unsafe abortions take place each year and account for
      approximately 13% of all maternal mortality and serious complications associated
      with it, such as sepsis, hemorrhage and trauma. Only a quarter of all women in
      the world do not have any access to legal abortion, whereas 40% have a legal
      right to decide for themselves. This liberalization of abortion legislation has
      seen a tremendous drop in abortion-related maternal mortality. Death from unsafe
      abortions are almost unknown in countries where abortion is available on request.
      Reduction of the need for induced abortion through the provision of good family
      planning services should be an integral part of healthcare. Consistent use of
      contraception greatly reduces the need for abortion, but it cannot completely
      eliminate this need. Thus, it is essential that safe medical abortion services
      should be made available to all women in the world in cases of contraceptive
      failure.

PMID- 10075223
TI  - Commercial availability of misoprostol and induced abortion in Brazil.
AB  - In Brazil, abortion is only permitted to save the woman's life or in cases of
      rape. The principal effect of legal restrictions is not to make induced abortion
      practice less prevalent but to force poor women to resort to abortions performed
      under unhygienic conditions or attempt self-induced abortion. Within this
      context, misoprostol, a synthetic analogue of prostaglandin E1, was introduced in
      the country in 1986. Purchased over the counter in pharmacies, misoprostol has
      became a popular abortifacient method among Brazilian women. By 1990, about 70%
      of women hospitalized with abortion-related diagnoses reported use of the drug.
      In 1991, the Ministry of Health restricted the sale of misoprostol, and in some
      states its use was totally banned. While the proportion of abortions induced with
      misoprostol has decreased, the drug continues to be sold on the black market at
      an inflated value. Research indicates that women have acquired more experience
      with the drug over time, resulting in lower doses and more effective
      administration. Several studies show that the rate and severity of complications
      are significantly less among women who used misoprostol compared with women who
      used invasive methods. Research also suggests that about half of the women have
      complete abortion with misoprostol, but seek medical care as soon as they have
      vaginal bleeding. The experience of Brazilian women with misoprostol is an
      example of how women when faced with unwanted pregnancy will resort to illegal
      abortion whatever the costs are to their health.

PMID- 10075224
TI  - Medical versus surgical abortion.
AB  - OBJECTIVE: To evaluate the safety, efficacy, and acceptability of an oral drug
      regimen of medical abortion compared with surgical abortion. MATERIALS AND
      METHODS: 500 women with amenorrhea < 56 days chose either surgical abortion or
      600 mg of mifepristone (RU-486) followed by 400 microg of misoprostol after 48 h.
      RESULTS: Medical regimen had more side effects than surgical abortion, including
      bleeding, cramping, nausea and vomiting. Only fever was more frequent in the
      surgical method. The failure rates for medical abortion exceeded those for
      surgical abortion, 16.0% vs. 4.0%. The adolescents' failure rate in the medical
      regimen group was only 1.7%. Several failures on medical abortion were not true
      drug failures, but surgical interventions not medically necessary (misdiagnosis).
      Women were satisfied with either method, but more preferred medical abortion.
      CONCLUSION: Medical methods are safe, effective, simpler and potentially allow
      greater privacy than surgical abortion methods. Therefore, medical methods could
      be the method of choice for abortion, particularly for adolescents.

PMID- 10075225
TI  - Teaching safe sex in school.
AB  - OBJECTIVE: To teach safe sex practices to adolescents in school, before they
      start to become sexually active, using peer group education. METHOD: To send
      young medical students back to their old schools to do the teaching, and to get
      them to make videos suitable for showing to teenage audiences that can be widely
      circulated to all schools. RESULTS: The program has been running in Australia
      since 1992, and has proved highly popular with school teachers, school children,
      and particularly with medical students. We are now working with medical schools
      in Beijing and Shanghai, at the invitation of the Chinese Ministry of Health, to
      see if we can adapt our program to a very different cultural setting. CONCLUSION:
      Educating children about Safe Sex is one of the most effective ways of postponing
      their onset of sexual activity. It is also the best investment that we can make
      to ensure people's future reproductive health; if they start right, there is
      every hope that they will stay right.

PMID- 10075226
TI  - Pregnancy during adolescence: wanted vs. unwanted.
AB  - Pregnancy among adolescents is an important problem in most developing countries.
      The phenomenon in Brazil seems numerically stable for the age group from 15 to 19
      years old, with a trend of increase in the first segment of adolescence, below
      15. The majority of pregnancies are unwanted, with medical, psychological and
      mainly social repercussions. The disadvantages are clearer for multipara
      adolescents. The main immediate consequences of an unwanted pregnancy are:
      induced abortion, lack of prenatal care, personal and family disruption, adoption
      and abandonment. Some intervention policies are suggested for the reduction of
      this phenomenon through programs of sexual education, services for special care
      of adolescents, access to orientation and contraceptive methods, and support for
      the pregnancies to be carried on until term.

PMID- 10075227
TI  - Sex education in school: preventing unwanted pregnancy in adolescents.
AB  - Sexual activity during adolescence may represent a risk for young women's quality
      of life as well as their health. This practice can result in early pregnancy,
      abortion, AIDS and other sexually transmitted diseases. The need for sexual
      education in order to identify and prevent the risk factors of an unwanted
      pregnancy during adolescence becomes increasingly clearer. In order to accomplish
      this purpose all segments of society shall be convened. If the goal is educating,
      informing or, even better, forming, then the school stands out from among the
      other reference groups because this is its essential role. A few basic principles
      should be established for the success of the educators' actions. Perhaps the most
      important one being not only to base sexual education on the use of preservatives
      and contraceptive methods, but rather on rescuing the individual as a result of
      his/her own actions. This favors the development of a sense of citizenship,
      respect, commitment, self-care and care for others.

PMID- 10075228
TI  - HIV: mother to child transmission, current knowledge and on-going studies.
AB  - It is estimated that approximately 6000 women of childbearing age, mostly living
      in the developing world, acquire HIV infection every day. Taking into account
      that approximately 98% of HIV infected children have acquired HIV from the
      mother, during pregnancy, at delivery or through breastfeeding, therefore,
      prevention of mother-to-child transmission (MTCT) is a major health priority.
      Several studies have showed how MTCT of HIV may be prevented using
      antiretrovirals. Results from a study conducted in Thailand have also recently
      showed how a short oral zidovudine course during pregnancy and labor may reduce
      the risk of HIV transmission by approximately 50%. These findings represent a
      major challenge for the International Health Agencies and Organizations that will
      have the major obligation to provide HIV tests, counseling and antiviral drugs in
      settings with high HIV prevalence.

PMID- 10075229
TI  - Sexually transmitted diseases and reproductive tract infections among
      contraceptive users.
AB  - OBJECTIVE: To establish the association between the use of contraceptives and the
      prevalence of sexually transmitted diseases (STD) and other reproductive tract
      infections (RTI). METHODS: 840 women who used contraception and who attended the
      Fundacao Nossa Senhora do Bom Sucesso's Family Planning Clinic (FNSBS-FPC) over a
      2-year period (1993-1994) were studied. All women answered a standard
      epidemiological survey and underwent a clinical laboratory assessment. The Chi
      square test and a logistic regression model were used for statistical analysis.
      RESULTS: The majority of women were young (58.7%); low educational achievers
      (59.0%); middle or working class (85.0%); had a fixed partner (79.8%), and were
      of non-African origin (95.6%). Of the 627 women who responded, 4.1% stated that
      their sexual behavior was of high risk. The prevalence of any infection and
      particularly of bacterial vaginosis (BV), was highest among users of the intra
      uterine device (IUD). Use of an IUD (P = 0.001) and high risk behavior (P = 0.04)
      were the variables associated to presence of a STD/RTI in multiple regression
      analysis. CONCLUSION: Results suggest that STD/RTIs basically occur due to high
      risk behavior and that, with the exception of an association between use of IUD
      and BV, the method of contraception does not affect the incidence of these
      infections.

PMID- 10075230
TI  - Changing behavior to prevent STDs/AIDS.
AB  - There is a growing body of evidence that theory-based behavioral interventions
      can effectively reduce risky behaviors that can lead to the acquisition and
      transmission of STDs/HIV. Despite the substantive uniqueness of any given
      behavior, there are only a limited number of theoretical variables that need to
      be considered in any attempt to produce behavior change. These variables are
      identified and two multi-site studies are described to illustrate how these
      variables can be used to guide the development of effective behavior change
      interventions in both community and clinic settings.

PMID- 10075231
TI  - Current approach to STD management in women.
AB  - HIV infection was recognized as a new sexually transmitted disease (STD) at the
      beginning of the last decade. The knowledge of risk factors for sexual
      transmission of HIV changed the focus on STD to a broader perspective for
      prevention and control of HIV infection, and consequently of STD. Barriers to STD
      control include cultural aspects, difficulties in changing sexual behavior,
      asymptomatic disease in women and expensive and inaccessible tests for diagnosis.
      The classical clinical approach based on etiologic treatment has never been
      achieved by developing countries. The international community has been searching
      for new approaches. Syndromic management and mass treatment are strategies
      recently found as useful. Nevertheless the best approach to endocervicitis by
      Neisseria gonorrhoeae and Chlamydia trachomatis remain problematic. Then, the
      current approach to STD management must include: prompt attention to every
      patient seeking care for STD; early diagnosis and treatment; delivery of short
      term treatment at the clinic; education on STD/HIV; screening for other STDs with
      pre- and post-test counseling; counseling on risk reduction; provision of
      condoms; integration of STD services with family planning, prenatal and
      gynecological services.

PMID- 10075232
TI  - In defence and pursuit of equity.

PMID- 10075233
TI  - In defense and pursuit of equity and efficiency.

PMID- 10075234
TI  - Pursuing equity without getting beat.

PMID- 10075235
TI  - Review of nursing turnover research, 1977-1996.
AB  - Turnover represents a major problem for health care services in terms of cost and
      quality of care given. As a result, turnover has been the subject of a large
      number of investigations. However, the variety of study populations, research
      methodologies, and inconsistent definitions and measurements of turnover lead to
      difficulties when attempting to compare studies. The purpose of this paper is to
      present: (1) a summary of turnover study methods and procedures, and (2) a
      summary of socio-demographic, organizational, and social support factors
      associated with turnover of nursing staff.

PMID- 10075236
TI  - Outcomes and effectiveness in reproductive health.
AB  - Measuring reproductive health is problematic. Awareness of the problems needs to
      be raised both among those collecting and those using data on reproductive
      health. This paper discusses two major measurement questions--one related to
      ascertainment and the other to attribution. The first question is to what extent
      the observed levels and patterns of reproductive health outcomes in women are
      valid as opposed to artefacts of the data sources and the data collection
      methods? The second question is can lack of evidence of effectiveness for any
      reproductive health intervention ever confidently be separated into no effects vs
      an inability to measure effects? Determining the effectiveness of health
      interventions is notoriously difficult. Reproductive health may not be a case for
      special pleading in the competition for scarce resources, but equally it should
      not be a case for special standards of proof of the effectiveness of
      interventions--standards which have not indeed been met by many other, and yet
      unquestioned, health care priorities. "What works" in reproductive health should
      in fact be judged from at least four different perspectives: from that of women
      and their families, health professionals, the scientific community, and national
      and international policy-makers.

PMID- 10075237
TI  - Compulsory medical service in Ecuador: the physician's perspective.
AB  - Compulsory medical service programs for physicians and other health care
      professionals have been installed in developing countries around the world. The
      underlying assumption for the creation of these programs is that the increased
      presence of physicians will improve the health status of rural populations which
      exhibit higher rates of morbidity and mortality compared to urban populations.
      This assumption, however, has been challenged by recent evaluative studies of
      compulsory service programs in Latin America. This paper reports on the
      physician's perspective of Ecuador's compulsory service program, known as
      medicatura rural. Based on responses to a self-administered questionnaire
      completed by 127 physicians who had fulfilled or were currently fulfilling their
      medicatura rural requirement, in-depth interviews with physicians and other
      officials, and visits to several rural placement sites, the paper examines some
      of the fundamental programmatic and logistical problems that have impeded the
      successful implementation of the program since its inception in 1970. While the
      majority of the physicians reported that the medicatura rural experience was both
      professionally and personally rewarding, many view the program as conceptually
      flawed with respect to its goal of improving the health status of rural
      communities. The physicians' suggestions for improving the medicatura rural,
      which elucidate some of the program's basic conceptual flaws and reflect the
      criticisms of compulsory medical programs in other Latin American countries, are
      discussed. Finally, Ugalde's (1988) recommendation for replacing compulsory
      medical service programs with a "rural health corps" is considered.

PMID- 10075238
TI  - When acculturation hurts: the case of immunization.
AB  - The study examined the relationship between the acculturation of Mexican American
      mothers in Texas and immunization status of their children between 3 and 24
      months of age. Mothers' acculturation, demographic characteristics, and
      immunization status of their children were assessed in in-person interviews with
      a sample of Mexican American respondents representative for Texas (n = 2193).
      Acculturation was measured with ten scales assessing oral and written language
      use, proficiency, and preference, music and TV viewing preferences, ethnic
      identity, place where a person was reared, and contacts with Mexico. Immunization
      status, defined according to the recommendation of the CDC Advisory Committee on
      Immunization Practices, was determined from official shot records obtained
      directly from respondents or, for respondents without records, obtained from
      their health care providers. Regression analysis revealed that acculturation
      significantly contributed to inadequate immunization status, even when
      socioeconomic status and other demographic covariates of acculturation were
      statistically controlled. Mediational analysis revealed that acculturation
      contributed to inadequate immunization through less positive attitudes toward
      immunization, a diminished sense of parental responsibility for children's
      immunization, and more perceived barriers to immunization. It is concluded that
      culture-specific beliefs encouraging childhood immunization should be fostered
      among Mexican Americans.

PMID- 10075239
TI  - Trends in health services utilization in eight provinces in China, 1989-1993.
AB  - Continued pursuit of market-oriented reforms in China seems to have resulted in
      increasing income disparities. This has raised concerns about possible declines
      in the use of health services by the poor. Using data from three waves of the
      China Health and Nutrition Survey (1989, 1991, 1993), we examine whether people
      age 20-45 in eight provinces became less likely to seek care when ill. We carried
      out three probit estimations of seeking care when ill; the predictor variables
      include individual and workplace characteristics, a measure of the severity of
      illness and community level factors. Health care is broadly defined to include
      basic level clinics as well as urban hospitals. We find no evidence that health
      care utilization is decreasing. Rather, for people in a community survey
      reporting mainly mild or moderate illness, health care continues to be
      accessible. We consider possible limits of our study and discuss extensively the
      implications of the use of illness reports from the three cross-sectional surveys
      as health status indicators.

PMID- 10075240
TI  - The development of a dementia process within the family context: the case of
      Alice.
AB  - Qualitative analysis was used to analyse a diary written over a period of two
      years by the sister of a dementia patient. The analysis is directed at the
      question of how a patient and a social network respond to each other during the
      dementia process. The diary highlights features in the development of the
      dementia process which receive scant attention in empirical studies: changes in
      the interaction process between patient and social network; a patient's residual
      capacities; a caregiver's perceived rewards of caregiving. We designated three
      phases in the interaction process: the phase of recognition, the stable phase and
      the phase of destabilization. This diary illustrates how a stable phase in the
      interaction between patient and primary caregiver can be established. The
      caregiver derived rewards by noticing and using the patient's residual capacities
      and by a feeling of being useful. In this case caregiving is not unidirectional.
      The quality of future support programmes may be enhanced by combining programmes
      aimed to influence patient's behaviour and to support caregivers.

PMID- 10075241
TI  - Sexual networks: the integration of social and genetic data.
AB  - New methods for studying sexual networks are presented, drawing upon routine
      procedures followed in genitourinary medicine clinics in the UK for tracing
      partners and identifying strains of infection. The routine social procedures were
      developed to incorporate a structured interview. The routine microbiological
      diagnosis of gonorrhoea was augmented by phenotyping and the development of new
      genetic techniques for the fine discrimination of gonococcal strains (opa
      typing). Selected results from a study in Sheffield, UK show that each method has
      limitations, when conducted separately, but these are minimised when the methods
      are combined. Moreover, the use of simple and routine methods of data collection
      resolve issues of scale and sample that have beset other network studies, as they
      provide a means of covering a larger and defined population. Popular concepts
      about these methods are discussed in the conclusion. The integrated approach
      employed in our research raises questions both about social methods, 'of people
      who lie, particularly when they talk about sex', and about microbiological
      methods, 'of genes that tell the truth' and bypass what people say and think
      altogether. We argue that these stereotypes are misleading insofar as they
      suggest that genetic techniques can substitute for the social, and we suggest
      that even the finest discrimination of organisms at the genetic level will never
      obviate the need for their interpretation in the light of social data.

PMID- 10075242
TI  - In the company of friends: peer influence on Thai male extramarital sex.
AB  - We explore some of the key social dynamics underlying patterns of male
      extramarital heterosexual behavior in Thailand. We analyze transcripts of focus
      group discussions and focused individual interviews conducted during 1993 and
      1994 with married men and women living in both urban and rural areas of central
      Thailand. We discern several pathways of peer influence on extramarital
      commercial sex patronage that are common across our sites and interpret these
      peer effects in light of contemporary theories of social influence and sexual
      behavior.

PMID- 10075243
TI  - The meaning of playing-related musculoskeletal disorders to classical musicians.
AB  - In creating and performing music, musicians can experience health problems from
      the high physical and psychological demands of their profession. Musculoskeletal
      disorders related to playing are painful, chronic and disabling conditions which
      are prevalent among classical musicians. The widespread study of the prevalence,
      etiology, and management of playing-related musculoskeletal disorders (PRMDs) is
      a recent development known as performing arts medicine. Despite the rapid
      development of this new field, it is unclear how musicians identify themselves as
      injured, and how they make decisions about what, if anything, to do about these
      disabling injuries. The aims of our study were two-fold. First, we aimed to
      provide musicians with the opportunity to define a PRMD in their own words.
      Second, we sought to understand the subjective meaning of the PRMD experience to
      musicians. Two key informants identified 30 study participants in Ontario and
      Quebec, Canada. As a form of data triangulation, participants included 27
      musicians and three health professionals. Data were collected in semi-structured
      interviews which lasted, on average, 40 min. Data were transcribed, and were
      manually coded and analyzed. Participants defined a PRMD as pain and other
      symptoms which are chronic, are beyond their control, and which interfere with
      their ability to play their instrument at their usual level. Participants
      distinguished between "normal", mild everyday aches and pains, and a PRMD.
      Although a PRMD is not a medically serious or life-threatening illness, it is
      devastating to musicians physically, emotionally, socially, and financially. The
      overall theme of suffering captures the meaning of these problems which threaten
      the identity of the musician. The findings of this study are consistent with
      other studies of the experience of work-related musculoskeletal disorders, and
      other illnesses.

PMID- 10075244
TI  - Diagnosing moral disorder: the discovery and evolution of fetal alcohol syndrome.
AB  - The diagnosis of fetal alcohol syndrome (FAS) was invented in 1973. This paper
      investigates the process by which a cluster of birth defects associated with
      exposure to alcohol in utero came to be a distinct medical diagnosis, focusing on
      the first ten years of the medical literature on FAS. Fetal alcohol syndrome was
      "discovered" by a group of American dysmorphologists who published the first case
      reports and coined the term FAS. However, the nature of the diagnosis and its
      salient symptoms were determined collectively over time by the medical profession
      as a whole. The paper traces the natural history of the diagnosis in the U.S.
      through five stages: introduction, confirmation and corroboration, dissent,
      expansion, and diffusion. FAS serves as an example of the social construction of
      clinical diagnosis; moral entrepreneurship plays a key role and the medical
      literature on FAS is infused with moral rhetoric, including passages from
      classical mythology, philosophy, and the Bible. FAS is a moral as well as a
      medical diagnosis, reflecting the broader cultural concerns of the era in which
      it was discovered, including a greater awareness of environmental threats to
      health, the development of fetal medicine, an emphasis on "the perfect child,"
      and a growing paradigm of maternal-fetal conflict.

PMID- 10075245
TI  - Social class, assets, organizational control and the prevalence of common groups
      of psychiatric disorders.
AB  - This study provides an update on the association between social class and common
      types of psychiatric disorder in the US. In addition to usual measures of social
      class, we provide hypotheses for the expectation that assets and organizational
      control are associated with specific varieties of psychiatric disorders (mood,
      anxiety, alcohol and drug use disorders). We analyzed two surveys. The National
      Comorbidity Survey conducted in 1990-1992 yielded 12-month prevalence rates in a
      probability sample of 8098 respondents in the 48 contiguous states. The
      Epidemiologic Catchment Area Follow-up conducted in 1993-1996 provided similar
      rates among 1920 East Baltimore residents. Analyses of the National Comorbidity
      Survey showed an inverse association between financial and physical assets and
      mood, anxiety, alcohol, and drug disorders. The Epidemiologic Catchment Area
      Followup provided additional evidence for the inverse association between
      financial and physical assets and anxiety, alcohol and drug disorders. Also in
      the Epidemiologic Catchment Area, lower level supervisors presented higher rates
      of depression and anxiety disorders than higher level managers. Inequalities in
      assets and organizational control, as well as typical measures of social class,
      are associated with specific psychiatric disorders. These constructs can provide
      additional explanations for why social inequalities in psychiatric disorders
      occur.

PMID- 10075246
TI  - Mortality variations in England and Wales between types of place: an analysis of
      the ONS longitudinal study. Office of National Statistics.
AB  - This study investigates the extent to which individuals, in England and Wales, in
      different types of place experience differential mortality once account is taken
      of personal (individual and household) social circumstances. Data comes from the
      Longitudinal Study of England and Wales of the Office of National Statistics, the
      respondents being a one percent national random sample of people aged between 25
      and 74 at the 1971 census, followed until the end of 1985. For males and females
      separately, differences in mortality are found for the 36 types of Craig-Webber
      classification in models which include, at the individual level, a number of
      demographic and socio-economic variables (women being classified by their own
      occupation). In general, for both males and females, the same types of place have
      elevated or lowered mortality. For males a (cross-level) interaction exists
      between the proportion in the area in professional social classes and individual
      social class, the effects of individual social class being larger in areas
      containing a higher proportion of those in professional occupations. For females
      mortality is negatively related to the proportion of car-ownership in the area.

PMID- 10075247
TI  - Linking measures of health gain to explicit priority setting by an area health
      service in Australia.
AB  - A demonstration project was undertaken to develop an integer programming model
      that could help a regional health authority to take into account data on service
      effectiveness when allocating resources to acute inpatient services. The model
      was designed to find the mix of services that would maximise health gain from the
      available resources, and so provide information that could be used to encourage
      hospitals to change their patient mix. It was developed in collaboration with an
      Area Health Service in New South Wales, Australia, with the aim of assessing its
      potential as a decision support tool. Acute inpatient services were categorised
      in the model using classes derived from the Australian National Diagnosis Related
      Groups (AN-DRG) classification and the classes developed by the Oregon Health
      Services Commission. Estimates for the effectiveness of each service was derived
      from the Oregon benefit data. Estimates of resource use were derived from AN-DRG
      data. The expected demand for each service was derived from local activity data.
      Various scenarios were developed to assess the potential of the model to support
      decision makers. These mimicked plausible policy options and tested the
      sensitivity of the results to changes in the data. The scenarios demonstrated the
      model could reveal the consequences of different policy options, but also
      suggested that the difference in the cost-effectiveness of services close to the
      margin would be small and so a rigid approach to priority setting is undesirable.
      Difficulties in developing the model also demonstrate that incorporating health
      gain data into resource allocation decisions will not be straight-forward for
      health planners.

PMID- 10075248
TI  - Beliefs related to breast health practices: the perceptions of South Asian women
      living in Canada.
AB  - Breast cancer is becoming a major concern for many South Asian women. Clinical
      observations of women from a South Asian community living in Canada revealed an
      under use of early detection strategies. The purpose of this qualitative
      ethnoscience study was to examine breast health practices from the perspective of
      South Asian women to provide a foundation for the development of culturally
      suitable breast health services for this group. Open-ended interviews were
      conducted with a convenience sample of 50 South Asian women over the age of 30
      who had not been diagnosed with breast cancer. Adequate representation of the
      main religious groups (i.e. Sikh, Hindu, Muslim and Christian) was ensured
      through sampling techniques. Analysis of translated interviews involved
      identification of themes and the development of a taxonomy to represent
      relationships among emerging cultural themes and domains. Four central domains of
      beliefs related to breast health practices were identified: beliefs about a
      woman's calling, beliefs about cancer, beliefs about taking care of your breasts
      and beliefs about accessing services. These beliefs hold important implications
      for how health promotion strategies should be structured and offered, In
      particular, attention must be paid to the language that is used to talk about
      breast cancer, the importance of the role of the family in women's health
      decisions and traditions related to using narratives to share information and
      advice.

PMID- 10075249
TI  - Health and access to care: perspectives of homeless youth in Baltimore City,
      U.S.A.
AB  - Homeless youth suffer from high rates of health problems, yet little is known
      about their perceptions of or context for their own health issues. In this study,
      a combination of qualitative techniques from participatory rural appraisal and
      rapid assessment procedures was used to investigate the perceptions of health
      needs of shelter-based youth in Baltimore, MD in the U.S.A. The most common youth
      identified health problems included STDs, HIV/AIDS, pregnancy, depression, drug
      use and injuries. These correlate well with more objective health status data for
      the same youth. The youth spoke of environmental safety threats of violence and
      victimization by adults, as well as racism and sexism in their lives. Youth
      reported that trusted adult figures such as grandmothers are important sources of
      health advice. Many homeless youth from less than ideal family situations remain
      in contact with and continue to seek advice from parents and other family
      members. Health interventions with urban street youth need to acknowledge the
      primacy of the social context for these youth, as well as the reality of violence
      as a daily health threat.

PMID- 10075250
TI  - Careseeking for illness in young infants in an urban slum in India.
AB  - Illness in infants in the first two months of life can take a precipitous life
      threatening course, and requires timely and appropriate medical assessment and
      management. We conducted a focused ethnographic study of illness in young infants
      and associated careseeking practices in an urban slum in New Delhi, India, in
      order to identify the constraints in securing effective care for severe illness
      in this age group. The findings suggest that maternal recognition of illness is
      not a limiting factor in the use of health care services for sick young infants
      in this setting. Mothers respond to a number of important signs of illness,
      including changes in the young infant's sleeping or feeding behavior, and they
      are usually prompt in seeking care outside the home. They are not able, however,
      to discriminate among the many sources of health care available in this setting,
      and give preference to local unqualified private practitioners. Most
      practitioners, including qualified medical practitioners, display critical
      failures in the assessment and management of sick young infants. The continuity
      and effectiveness of care is further compromised by the caretakers' expectations
      of rapid cure, which result in discontinued treatment courses and frequent
      changes in practitioners, and by their reluctance to seek hospital care. The
      implications of these findings for the design of programs to reduce young infant
      mortality are discussed. In particular, the feasibility and acceptability of
      hospital referrals according to current program guidelines are called into
      question.

PMID- 10075251
TI  - Stories of meaning: lay perspectives on the origin and management of noninsulin
      dependent diabetes mellitus among older women in the United States.
AB  - Researchers have sought to explain nonadherence to standard medical regimens by
      investigating a variety of sociodemographic variables, and, less often, by
      exploring variations between the health perspectives and life circumstances of
      the individual. While divergence between lay and professional perspectives on the
      etiology and treatment of chronic diseases, such as noninsulin dependent diabetes
      mellitus, may possibly account for the documented low rates of adherence to
      biomedical recommendations, health beliefs and activities are best understood as
      connected to an individual's personal history and circumstances. In order to
      evaluate the relationship between causal explanation of NIDDM and adherence,
      ethnographic interviews were conducted among 51 older (65+) women with diabetes
      and their physicians. We chose to investigate adherence to dietary
      recommendations because it represents one of the most challenging lifestyle
      modifications and is particularly important to maintaining glycemic control. The
      interviews involved ethnomedical and food frequency intake questionnaires and
      semi-structured interviews. Results reveal a stronger association between dietary
      adherence and etiological perspectives on diabetes than any sociodemographic
      factors, including ethnicity, education and income or other health belief
      factors. Informants suggested five categories that they believed were responsible
      for the onset of their NIDDM; poor past dietary practices (n = 22); familial
      tendency to have diabetes (n = 10); improper bodily functioning (n = 10);
      personal risk factors (n = 6); and currently being overweight (n = 3). Analyses
      indicated that those who implicate former dietary practices, currently being
      overweight, or having improper bodily functions were more likely to follow a
      standard recommended diet for individuals with diabetes. These findings also
      highlight the attempt by individuals with NIDDM to create 'stories' of meaning of
      their diabetes by linking their current management strategies for NIDDM with past
      practices and history. In addition, our results question the utility of the
      'biomedical/alternative' labels.

PMID- 10075252
TI  - Radio and the commodification of natural medicine in Ecuador.
AB  - This paper explores the discourse that is being created around medical
      commodities in one Ecuadorian city in an effort to understand how desire for new
      medical products is generated and sustained. Commercial natural medicine, which
      includes vitamins, herbal remedies and tonics is a relatively new addition to the
      medical marketplace in Ecuador, yet the popularity of these products seems to be
      growing rapidly. Much of the success of natural medicines is due to promotional
      campaigns, most notably radio programs, that emphasize and manipulate, important
      cultural themes about the body, identity, morality and social success. Although
      on the surface natural medicine seems to be creating a radically new discourse
      about the body and illness causation, that discourse ultimately serves only to
      reinforce the unequal social relations associated with capitalist marketplaces.

PMID- 10075253
TI  - The centenary of discovery of radium.
AB  - Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at
      the Paris Academy of Science on 26th December 1898. One century later, radium has
      been abandoned, mainly for radiation protection difficulties. It is, however,
      likely that modern techniques of brachytherapy have inherited to those designed
      for radium sources, and that radium has cured thousands and thousands patients
      all over the world for about eighty years. The history of discovery and medical
      use of radium is summarised.

PMID- 10075254
TI  - Marie Curie--the founder of the Radium Institute in Warsaw.

PMID- 10075255
TI  - The hazy dawn of brachytherapy.
AB  - The discovery of radium by Pierre and Marie Curie in December 1898 opened a new
      era in science and within a few years provided medicine with a new means of tumor
      treatment. Their personal contribution to the start and early development of
      clinical applications should not be overlooked. The Curies did not limit their
      support to providing radium sources to medical pioneers but took a deep interest
      in the horizons of radium therapy. Pierre was one of the first to search for and
      demonstrate a biological effect of radium radiation. He investigated the
      radioactivity of the waters of hydrotherapeutic resorts. Marie took care of the
      measurement of the medical sources personally, convinced that the result of the
      treatment depends on the precise knowledge of the amount of radium applied. Her
      perseverance resulted in the establishment of the Institut du Radium (1909) in
      which, besides the physico-chemical laboratory, a biological department was set
      up. The latter became the Fondation Curie (1920), a leading medical center of
      treatment and training, with an integrated team of physicists, radiobiologists
      and clinicians led by Regaud. One hundred years after the discovery of radium,
      patients benefit today from the extensive clinical experience that has been
      collected over the years and from sophisticated developments in application
      techniques, dosimetry and quality assurance; the professional risk has been
      precisely assessed and the improvements in material and procedure have enabled
      the medical personnel to work in hazard-free conditions. This outcome results
      from the continuous progress that the pioneers gave impulse to. This paper
      intends to recall their efforts and achievements, as well as the difficulties and
      the problems they encountered during the first 2 decades when the sturdy
      foundations of brachytherapy were built.

PMID- 10075256
TI  - Prediction of overall pulmonary function loss in relation to the 3-D dose
      distribution for patients with breast cancer and malignant lymphoma.
AB  - PURPOSE: To predict the changes in pulmonary function tests (PFTs) 3-4 months
      after radiotherapy based on the three-dimensional (3-D) dose distribution and
      taking into account patient- and treatment-related factors. METHODS: For 81
      patients with malignant lymphoma and breast cancer, PFTs (VA, VC, FEV1 and
      TL,COc) were performed prior to and 3-4 months after irradiation and dose-effect
      relations for early changes in local perfusion, ventilation and air-filled
      fraction were determined using correlated CT and SPECT data. The 3-D dose
      distribution of each patient was converted into four different dose-volume
      parameters, i.e. the mean dose in the lung and three overall response parameters
      (ORPs, which represent the average local injury over the complete lung). ORPs
      were determined using the dose-effect relations for early changes in local
      perfusion, ventilation and air-filled fraction. Correlation coefficients were
      calculated between these dose-volume parameters and the changes in PFTs. In
      addition, the impact of the variables chemotherapy (MOPP/ABV and CMF), tamoxifen,
      smoking, age and gender on the relation between the mean lung dose and the
      relative changes in PFTs following radiotherapy was studied using multiple
      regression analysis. RESULTS: The mean lung dose proved to be the easiest
      parameter to predict the reduction in PFTs 3-4 months following radiotherapy. For
      all patients the relation between the mean lung dose and the changes in PFTs
      could be described with one regression line through the origin and a slope of 1%
      reduction in PFT for each increase of 1 Gy in mean lung dose. Smoking and CMF
      chemotherapy influenced the reduction in PFTs significantly for VA and TL,COc,
      respectively. Patients treated with MOPP/ABV prior to radiotherapy had lower pre
      radiotherapy PFTs than other patient groups, but did not show further
      deterioration after radiotherapy (at 3-4 months). CONCLUSIONS: The relative
      reduction in VA, VC, FEV1 and TL,COc 3-4 months after radiotherapy for breast
      cancer and malignant lymphoma can be estimated before radiotherapy based on the
      mean lung dose of each individual patient and taking into account the use of
      chemotherapy and smoking habits of the patient.

PMID- 10075257
TI  - Pulmonary function following adjuvant chemotherapy and radiotherapy for breast
      cancer and the issue of three-dimensional treatment planning.
AB  - BACKGROUND AND PURPOSE: The frequency and grade of pulmonary complications
      following adjuvant radiotherapy for breast cancer are still debated. This study
      focuses on loss of pulmonary function. MATERIALS AND METHODS: We have measured
      the reduction of pulmonary function 5 months following radiotherapy in 144 node
      positive stage II breast cancer patients by using pulmonary function tests.
      RESULTS: No deterioration of pulmonary function was detected among the patients
      who were treated with local radiotherapy. On the contrary, there was a mean
      increase in diffusion capacity by 7% (P = 0.004) following radiotherapy, which
      most likely was explained by the adjuvant chemotherapy administered prior to the
      baseline pulmonary function tests. Patients undergoing loco-regional radiotherapy
      showed a mean reduction in diffusion capacity by 5% (P < 0.001) and in vital
      capacity by 3% (P = 0.001). The subset of patients (9%) who were diagnosed with
      severe pulmonary complications needing cortisone treatment had significantly
      larger mean paired differences in vital capacity (-0.446 L, -15% (equivalent to
      15 years of normal ageing or the loss of 3/4 of a lung lobe)) compared to the
      patients who were asymptomatic (-0.084 L) (P < 0.05). When the effects of
      potential confounding factors and different radiotherapy techniques were tested
      on the reduction of pulmonary function by stepwise multiple regression analysis,
      a significant correlation was found only to locoregional radiotherapy including
      the lower internal mammary lymph nodes. CONCLUSIONS: We conclude that a
      clinically important reduction of pulmonary function is seen in the subset of
      patients who are diagnosed with severe pulmonary complication following loco
      regional radiotherapy for breast cancer. The results of this study warrant
      further studies based on individual lung dose volume histograms.

PMID- 10075258
TI  - Practical implementation of compensators in breast radiotherapy.
AB  - BACKGROUND AND PURPOSE: A method of using electronic portal imaging to design
      compensators for tangential breast irradiation has been developed. We describe
      how this has been implemented. MATERIALS AND METHODS: The compensator design
      method generates wedged and unwedged beam weights, in conjunction with templates
      for multiple lead-sheet compensators and pseudo-CT outlines. The latter describe
      the breast and lung profiles in a set of transverse slices. The layers of the
      compensator and pseudo-CT outlines are transferred to a treatment planning system
      for verification. The accuracy of the planning system for the high transmission
      blocks used to describe the compensators has been verified using a plotting tank
      system. Dose volume histogram data and transaxial and sagittal plan slices have
      been compared for both standard and compensated treatments for a sample set of
      five patients. RESULTS: The planning system predicted the dose at depths of 1.5
      and 5 cm to within 2% for the compensators tested. The biggest source of
      discrepancy was a consequence of the planning system requiring blocks to have
      integer percentage transmission. For all patients studied, the compensated
      treatment resulted in a significant reduction in the percentage volume outside
      the 95-105% dose, with an average reduction of 10.2%. The percentage volume
      outside the 95-107% dose was also reduced by typically 3.4%. The implementation
      was found to yield a convenient automatic method of designing compensators using
      electronic portal imaging and verifying the results using a planning system.
      CONCLUSIONS: These results indicate that this method of implementation can be
      used in practice. The dosimetric accuracy of the treatment planning system is
      limited by the requirement that blocks should be of integer transmission, but
      this effect is small.

PMID- 10075259
TI  - A paired wedge filter system for compensation in dose differences.
AB  - OBJECTIVE: In radiotherapy, it is important to conform the high dose volume to
      the planned target volume. A variable thickness paired wedge filter system was
      developed to compensate for dose inhomogeneity arising from field width segment
      variation in conformal irradiation. MATERIALS AND METHODS: The present study used
      a 6 MV linear accelerator equipped with multileaf collimator leaves and a paired
      wedge compensating filter system. The dose variation due to field width was
      measured in each field segment width. The variation in attenuation of the
      compensators was measured as a function of filter position. As the field width
      increases, the relative absorbed dose also increases; this is the point of
      requiring compensation, so it can be in reverse proportion. RESULTS: As the field
      width increases, the relative absorbed dose also increases; this is why
      compensation is required and thus it must be in reverse proportion. Attenuation
      of the absorbed dose by the paired filters was in proportion to the filter
      position. The filter position to compensate for the difference of absorbed doses
      was defined by the square root of the field width. For a field varying in width
      from 4 to 16 cm, the variation in the absorbed dose across the field was reduced
      from 12% to 2.7%. CONCLUSION: This paired wedge filter system reduced absorbed
      dose variations across multileaf collimator shaped fields and can facilitate
      treatment planning in conformal therapy.

PMID- 10075260
TI  - The effect of independent collimator misalignment on the dosimetry of abutted
      half-beam blocked fields for the treatment of head and neck cancer.
AB  - BACKGROUND AND PURPOSE: Independent collimation conveniently allows for the
      junctioning of abutting fields with non-diverging beam edges. When this technique
      is used at the junction of multiple fields, e.g. lateral and low anterior fields
      in three-field head and neck set-ups, there should be a dosimetric match with no
      overdose or underdose at the matchline. We set out to evaluate the actual
      dosimetry at the central match plane. MATERIALS AND METHODS: Independent jaws
      were used to mimic two half-beam blocked fields abutting at the central axis. X
      Ray verification film was exposed in a water-equivalent phantom and the dose at
      the matchline was evaluated with laser densitometry. Collimators were then
      programmed to force a gap or overlap of the radiation fields to evaluate the
      effect of jaw misalignment within the tolerance of the manufacturer's
      specification. Diode measurements of the field edges were also performed. Four
      beam energies from four different linear accelerators were evaluated. RESULTS:
      Small systematic inhomogeneities were found along the matchline in all linear
      accelerators tested. The maximum dose on the central axis varied linearly with
      small programmed jaw misalignments. For a gap or overlap of 2 mm between the
      jaws, the matchline dose increased or decreased by 30-40%. The region of overdose
      or underdose around the matchline is 3-4 mm wide. The discrepancy between the
      width of jaw separation and the width of the region of altered dose is explained
      by a penumbra effect. CONCLUSION: We recommend that independent jaw alignment be
      evaluated routinely and provide a simple method to estimate dose inhomogeneity at
      the match plane. If there is a field gap or overlap resulting in a clinically
      significant change in dosimetry, jaw misalignment should be corrected. If it
      cannot be corrected, part of the benefit of asymmetric collimation is lost and
      other methods of field junctioning may have to be considered. We routinely use a
      small block over the spinal cord at the mono-isocenter set-up plane for three
      field head and neck treatments to prevent an overdose.

PMID- 10075261
TI  - Individualized phantom based on CT slices and auxological data (ICTA) for dose
      estimations following radiotherapy for skin haemangioma in childhood.
AB  - BACKGROUND AND PURPOSE: Before 1974 about 5000 children were treated by
      radiotherapy at the Institut Gustave-Roussy (IGR) for a skin haemangioma. A human
      model whose characteristics are as close as possible to those of the patient at
      the time of the treatment is necessary to effectuate an accurate retrospective
      estimation of the radiation doses received at distant organs. METHODS: We have
      developed a software package which constructs an individualized phantom based on
      CT slices and auxological data (ICTA) for this purpose. A set of real CT slices
      is used to produce a 3-D representation of the human body which is then adjusted
      to fit the dimensions supplied by published auxological data relative to sex and
      age for each patient. One hundred sixty-one anatomical landmarks of
      epidemiological interest have been defined inside the phantom for dose
      estimation. RESULTS: The transverse, frontal and sagittal views of the phantom
      displayed permit accurate positioning of radioactive applicators. The software
      calculates the relevant parameters required for dose estimation based on the
      patient's probable anatomy.

PMID- 10075262
TI  - Assessment of dose inhomogeneities in clinical practice by film dosimetry.
AB  - AIM: To use portal images acquired in routine circumstances for assessment of
      midplane dose variations in the patient. MATERIAL AND METHODS: Optical density
      readings are performed on routinely acquired Verification films of breast and ear
      nose-throat (ENT) cancer patients and these readings are converted into relative
      doses with the sensitometric curve. ( 1 ) The impact of redistribution is
      evaluated on films taken close to the patient exit surface and at routine focus
      film distance. (2) Midplane doses are estimated from film readings to assess dose
      variations in the patient. The influence of wedges is evaluated. Film
      measurements doses are compared with calculated exit doses. RESULTS: (1) In
      regions with large variations in the distance between the patient exit surface
      and the film but without inhomogeneities in tissue density, the relative doses
      distributions read on films acquired at large focus-film-distance (FFD) are
      proportional to exit doses. In regions with flat exit surfaces but with
      inhomogeneities in tissue density, the redistribution has only a small impact.
      (2) Large variations in relative midplane doses were found in both breast (85
      115%) and ENT (-3.6 to +15%) patients. The application of a wedge was shown to
      increase dose homogeneity in the midplane. A good agreement (differences < 3%)
      was found between exit doses obtained from film readings and exit doses
      calculated with the treatment planning system (TPS). CONCLUSION: Films acquired
      in routine circumstances at large FFD can be used to obtain information on exit
      doses and to assess midplane doses in breast and ENT, without the use of a TPS.
      Film dosimetry can also provide a quality assurance tool to check actually
      delivered doses in patients by comparing exit doses estimated on film to expected
      exit doses calculated by the TPS.

PMID- 10075263
TI  - Planning of beam intensity modulation using an advanced 3D dose calculation
      algorithm and a simulated annealing method.
AB  - PURPOSE: The aim of this work was to develop a fast inverse planning algorithm
      that will calculate optimum beam intensity distributions and beam shapes, and to
      incorporate the algorithm into a three-dimensional CT planning system. METHOD:
      The algorithm is based on the technique of simulated annealing and produces beam
      intensity distributions that could in principle be implemented clinically, either
      by the use of compensators or dynamic multileaf collimation. Dose distributions
      are calculated using a voxel beam model based on a spherical co-ordinate system,
      and transformations are given allowing the dose to be determined at any point
      within the patient. The dose calculation algorithm calculates primary and
      scattered dose separately from a knowledge of tissue/air ratios and differential
      scatter/air ratios, and both are corrected for the presence of heterogeneities in
      three dimensions. Specific attention is given to the execution time of the
      algorithm, and the methods developed allow satisfactory results to be achieved in
      calculation times which are sufficiently fast to be used interactively in the
      planning system. Several objective functions have been developed and can be
      selected in a simple manner by the user. In general, these attempt to achieve a
      uniform dose within the target while limiting the dose to organs at risk, either
      by upper dose limits or by specifying constraints on their dose volume
      histograms. RESULTS: The beam intensity distributions produced from the
      optimization have been used automatically by the forward planning system to
      produce three-dimensional dose distributions, and the results obtained in a
      number of clinical situations are presented. CONCLUSIONS: The inverse planning
      algorithm developed has been successfully incorporated into a three-dimensional
      planning system and is capable of producing beam intensity modulated
      distributions for clinical implementation. The execution time of the algorithm is
      sufficiently fast to be used as an optimization tool in an interactive forward
      planning system.

PMID- 10075264
TI  - Quantitative dosimetric verification of an IMRT planning and delivery system.
AB  - BACKGROUND AND PURPOSE: The accuracy of dose calculation and delivery of a
      commercial serial tomotherapy treatment planning and delivery system (Peacock.
      NOMOS Corporation) was experimentally determined. MATERIALS AND METHODS: External
      beam fluence distributions were optimized and delivered to test treatment plan
      target volumes, including three with cylindrical targets with diameters ranging
      from 2.0 to 6.2 cm and lengths of 0.9 through 4.8 cm, one using three cylindrical
      targets and two using C-shaped targets surrounding a critical structure, each
      with different dose distribution optimization criteria. Computer overlays of film
      measured and calculated planar dose distributions were used to assess the dose
      calculation and delivery spatial accuracy. A 0.125 cm3 ionization chamber was
      used to conduct absolute point dosimetry verification. Thermoluminescent
      dosimetry chips, a small-volume ionization chamber and radiochromic film were
      used as independent checks of the ion chamber measurements. RESULTS: Spatial
      localization accuracy was found to be better than +/-2.0 mm in the transverse
      axes (with one exception of 3.0 mm) and +/-1.5 mm in the longitudinal axis.
      Dosimetric verification using single slice delivery versions of the plans showed
      that the relative dose distribution was accurate to +/-2% within and outside the
      target volumes (in high dose and low dose gradient regions) with a mean and
      standard deviation for all points of -0.05% and 1.1%, respectively. The absolute
      dose per monitor unit was found to vary by +/-3.5% of the mean value due to the
      lack of consideration for leakage radiation and the limited scattered radiation
      integration in the dose calculation algorithm. To deliver the prescribed dose,
      adjustment of the monitor units by the measured ratio would be required.
      CONCLUSIONS: The treatment planning and delivery system offered suitably accurate
      spatial registration and dose delivery of serial tomotherapy generated dose
      distributions. The quantitative dose comparisons were made as far as possible
      from abutment regions and examination of the dosimetry of these regions will also
      be important. Because of the variability in the dose per monitor unit and the
      complex nature of the calculation and delivery of serial tomotherapy, patient
      specific quality assurance procedures will include a measurement of the delivered
      target dose.

PMID- 10075265
TI  - Dose rate correction in medium dose rate brachytherapy for carcinoma cervix.
AB  - PURPOSE: To establish the magnitude of brachytherapy dose reduction required for
      stage IIB and III carcinoma cervix patients treated by external radiation and
      medium dose rate (MDR) brachytherapy at a dose rate of 220+/-10 cGy/h at point A.
      MATERIALS AND METHODS: In study-I, at the time of MDR brachytherapy application
      at a dose rate of 220+/-10 cGy/h at point A, patients received either 3060 cGy, a
      12.5% dose reduction (MDR-12.5), or 2450 cGy, a 30% dose reduction (MDR-30), to
      point A and they were compared to a group of previously treated LDR patients who
      received 3500 cGy to point A at a dose rate of 55-65 cGy/h. Study-II was a
      prospective randomized trial and patients received either 2450 cGy, a 30% dose
      reduction (MDR-II (30)) or 2800 cGy, a 20% dose reduction (MDR-II (20)), at point
      A. Patients were evaluated for local control of disease and morbidity. RESULTS:
      In study-I the 5-year actuarial local control rate in the MDR-30 and MDR-12.5
      groups was 71.7+/-10% and 70.5+/-10%, respectively, compared to 63.4+/-10% in the
      LDR group. However, the actuarial morbidity (all grades) in the MDR-12.5 group
      was 58.5+/-14% as against 34.9+/-9% in the LDR group (P < 0.05). Similarly, the
      grade III and IV morbidity also in the MDR-12.5 group was 12.5+/-9% as against
      5.3+/-5% in the LDR group (P < 0.05). No statistically significant difference in
      morbidity was seen between the MDR-30 and LDR groups. In study-II the 3-year
      actuarial local control rate in the MDR-II (30) and MDR-II (20) groups was 66.6+/
      10% and 74.8+/-9%, respectively. There was a significant correlation between the
      rectal BED received and the percentage of patients developing rectal morbidity.
      Only 10% of patients receiving a rectal BED of (100 < 120) Gy3 developed
      complication as against 62.5% of those receiving a rectal BED of (140 < 160) Gy3
      (chi2 = 46.43; P < 0.001). CONCLUSION: We suggest that at a dose rate of 220+/-10
      cGy/h at point A the brachytherapy dose reduction factor should be around 30%, as
      suggested by radiobiological data, to keep the morbidity as low as possible
      without compromising the local control rates.

PMID- 10075266
TI  - Effect of electrolyte and solvent composition on capillary electrophoretic
      separation of some pharmaceuticals in non-aqueous media.
AB  - Non-aqueous capillary electrophoresis was used to study the separation
      selectivity of positively charged drug substances and negatively charged
      diuretics. Study was made of the effects of organic solvent composition and the
      background electrolyte on the separation. The separation selectivity could be
      altered considerably by varying the methanol/acetonitrile composition. In
      addition, the migration order and the resolution of the pharmaceuticals could be
      altered merely by changing the electrolyte cation or the anion. The electrolytes
      tested were alkali metal acetates, ammonium acetate, ammonium chloride and
      ammonium bromide. As with aqueous background electrolyte solutions, the
      electroosmotic flow was decreased with increasing size of the alkali metal cation
      of the electrolyte in methanol/acetonitrile 50:50 (v/v).

PMID- 10075267
TI  - Analysis of lipophilic peptides and therapeutic drugs: on-line-nonaqueous
      capillary electrophoresis-mass spectrometry.
AB  - This minireview addresses the usefulness of nonaqueous capillary electrophoresis
      mass spectrometry (NACE-MS), mainly in the analysis of lipophilic peptides such
      as gramicidin S and bacitracin, and therapeutic drugs such as pyrazoloacridine,
      the H2-antagonist mifentidine, tamoxifen, and their metabolites. The beneficial
      effects of NACE-MS in typical bioanalytical applications are analyzed case by
      case. A suitable and widely applicable NACE-MS analysis is identified, which is
      an electrolyte buffer containing ammonium acetate (5-50 mM) and/or acetic acid
      (up to 100 mM) with varying composition of organic solvents. Either acetonitrile
      or methanol or a mixture of the two are mostly utilized in the nonaqueous media.
      Primary considerations in developing NACE-MS are also discussed.

PMID- 10075268
TI  - Ionization constants of weak acids and bases in organic solvents.
AB  - A discussion of the influence of organic solvents on pKa values is presented.
      Enthalpy and entropy of ionization in organic solvents are compared with aqueous
      systems. The impact of the solvent on the ionization constants is interpreted
      based on the free energy of transfer applied to all particles involved in the
      ionization reaction of acids and bases, and the concept of the 'medium effect' on
      these species. The limitation of Born's approach (which takes into account only
      electrostatic effects on the ionization equilibrium) is demonstrated and the
      importance of solute-solvent interactions on the change of the pKa values
      emphasized.

PMID- 10075269
TI  - Non-aqueous capillary electrophoresis of drugs: properties and application of
      selected solvents.
AB  - The electrophoretic mobility of selected acidic and basic test solutes have been
      determined in non-aqueous media prepared by adding various combinations of
      ammonium acetate, sodium acetate, methane sulphonic acid and acetic acid to
      acetonitrile, propylene carbonate, methanol, formamide, N-methylformamide, N,N
      dimethylformamide and dimethylsulphoxide, respectively. The apparent pH (pH*) of
      these non-aqueous media have been measured and it was found that pH* is an
      important factor for the separations in non-aqueous capillary electrophoresis.
      However, in some solvents the concentration of sodium acetate has a strong
      influence on the mobility despite very small changes in pH*. Due to the fact that
      a change in one parameter influences a number of other parameters it is very
      difficult to conduct systematic studies in non-aqueous media and to compare the
      migration of the species at fixed pH* values from one solvent to another. Thus
      pH* is only of value for comparison when used with a specific solvent or solvent
      mixture. The viscosity of the above-mentioned solvents were measured at various
      temperatures and means to adjust the viscosity of the non-aqueous media used for
      capillary electrophoresis are discussed and the separation of ibuprofen and its
      major metabolites in urine is used as an example.

PMID- 10075270
TI  - Fast separation of 16 seizure drug substances using non-aqueous capillary
      electrophoresis.
AB  - A fast and simple method for separation of 16 seizure drug substances using
      capillary electrophoresis in a non-aqueous separation medium is described. The
      separation medium consists of a mixture of acetonitrile, methanol and glycerol
      with ammonium acetate/acetic acid as the electrolyte. The analytes are detected
      by UV detection at 214 nm. Injection from the detection end (8.5 cm to detector)
      combined with the usage of a short capillary (32.5 cm total length) makes it
      possible to separate all 16 amines within 2 min. The choice of solvents,
      electrolytes and viscosity increasing additives are discussed with special
      emphasis to their influence on the separation selectivity.

PMID- 10075271
TI  - Torulopsis glabrata an emerging yeast pathogen in cancer patients.

PMID- 10075272
TI  - Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia:
      a commentary.
AB  - Whether combination antimicrobial therapy is more efficacious than monotherapy
      for gram-negative bacteraemia remains controversial. Although there are
      theoretical advantages to combination therapy that are buttressed by in vitro and
      animal studies, the data from studies of patients with gram-negative bacteraemias
      have been conflicting. A review of selected clinical studies suggests that
      combination therapy is associated with improved outcome typically only in
      severely ill patients and its efficacy may be further limited to those with
      Pseudomonas aeruginosa, Klebsiella spp. or Enterobacter spp. bacteraemia.

PMID- 10075273
TI  - Efficacy and safety of combination therapy with delavirdine and zidovudine: a
      European/Australian phase II trial.
AB  - The objective of the study was to investigate the safety and antiviral effect of
      three delavirdine dose regimens or placebo in combination with zidovudine in
      patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1
      seropositive individuals with CD4 cell counts between 50 and 350 cells/microl
      were included in this trial The influence of combination therapy on viral
      susceptibility to both zidovudine and delavirdine was investigated. Death or the
      occurrence, or re-occurrence of an AIDS-defining illness was considered as a
      clinical endpoint. The addition of delavirdine to the antiretroviral treatment
      regimen resulted in a significant, but transient, reduction in virus load, as
      determined by quantitative RNA measurements. CD4+ cell count did not change
      significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of
      combination therapy, while 70% of the patients demonstrated a substantial
      decrease (> 10-fold) in sensitivity to delavirdine. Two patients suffered from an
      AIDS-defining disease during the study. No deaths occurred. Generally, the drug
      appeared to be safe. Skin rash was the most frequently observed adverse event
      (52%). In most patients the rash either resolved spontaneously or was treated
      successfully with a short course of antihistamines. The definite place of the
      compound in the management of HIV disease, in particular when given in
      combination with other antiretroviral agents, remains to be further explored.

PMID- 10075274
TI  - Antibiotic usage in primary care units in Taiwan.
AB  - To understand the situation of antibiotic usage in primary care units in Taiwan,
      we collected all prescriptions over a 1 week period during March 2 to March 7,
      1992, December 2 to December 7, 1992, and January 14 to January 19, 1994 from out
      patient clinics of public health stations located in various parts of Taiwan. In
      the first time period 60 health stations were sampled, 18,350 patient-visits made
      and 23,674 diagnoses recorded. In the second time period 168 health stations were
      sampled, 84,143 patient-visits made and 96,528 diagnoses recorded. In the third
      time period 173 health stations were sampled with 85,623 patient-visits and
      105,132 diagnoses recorded. The percentages of total patient-visits that resulted
      in antibiotic treatment were 16.7, 13.5 and 12.4% in the three time periods,
      respectively. The patient group under the age of 11 received the highest
      percentage of antibiotic treatment. The percentage of patient-visits that
      resulted in treatment with two or more types of antibiotics decreased from 25.4%
      in March, 1992 to 13.2% in January, 1994. Common cold was the most frequent
      diagnosis in patients receiving antibiotic therapy during the three time periods
      and accounted for 36.9% of total antibiotic prescriptions. Of the patients with
      the diagnosis of common cold, 29.7% received antibiotic treatment, of whom the
      largest group were paediatric patients (< 16 years). Penicillins, macrolides and
      cephalosporins were the most commonly prescribed antibiotics and accounted for
      34.0, 21.8 and 21.3% of all prescribed antibiotics in the three study periods.

PMID- 10075275
TI  - Interferon-gamma effects on activities of gentamicin and vancomycin against
      Enterococcus faecalis resistant to the drugs: an in vitro study with human
      neutrophils.
AB  - The emergence of multidrug-resistant enterococci presents a major therapeutic
      challenge since there is currently no clearly effective antimicrobial therapy for
      these infections. The combinatorial effects of interferon-gamma (IFN-gamma) with
      gentamicin and/or vancomycin against a clinical isolate of drug-resistant
      Enterococcus faecalis, were evaluated in an in vitro system with human
      neutrophils. Following inoculation of cultures of human neutrophils with the
      organism, treatments were initiated immediately after the infection and the
      number of viable bacteria was determined at 12, 18 and 24 h. Antibiotics were
      applied at concentrations close to their clinically achievable serum trough and
      peak levels. Treatment with IFN-gamma alone induced a maximal growth inhibition
      of up to 40% at a concentration of 100 U/ml. Addition of the cytokine to either
      therapeutic trough or peak concentrations of gentamicin and vancomycin, or a
      combination of both antimicrobials, was associated with a significant (P < 0.01)
      enhancement of anti-enterococcal activity compared with the effects of the agents
      alone. Investigation of a potential underlying mechanism of anti-enterococcal
      action of IFN-gamma reveals that it is, most probably, largely due to an
      activated secretion of the microbicidal reactive oxygen intermediates by
      neutrophils. The results of this study show that there is a possibility that IFN
      gamma could be a useful adjunct in the treatment of multidrug-resistant E.
      faecalis.

PMID- 10075276
TI  - Improved efficacy with nonsimultaneous administration of netilmicin and
      minocycline against methicillin-resistant Staphylococcus aureus in in vitro and
      in vivo models.
AB  - The effect of combined administration of netilmicin and minocycline against
      methicillin-resistant Staphylococcus aureus (MRSA) was investigated by using in
      vitro and in vivo models. Thirty one isolates of MRSA were tested for sensitivity
      to netilmicin, minocycline, and combination of both by the chequer board method.
      We used then a dynamic in vitro system, which simulates in vivo serum kinetics,
      to assess the effect of various combination regimens of these antibiotics against
      an MRSA isolate with a fractional inhibitory concentration index of 0.25. The
      following dose regimens were compared: netilmicin given alone; minocycline given
      alone; both antibiotics given simultaneously; netilmicin followed by minocycline
      at 2 h; or minocycline followed by netilmicin at 2 h. Netilmicin showed a
      stronger activity than minocycline. On the other hand, their combination was
      synergistic against 19% of isolates and additive against 77% of isolates. Against
      one isolate only, it was indifferent, and no antagonism was observed. In the auto
      simulation system, the combination of antibiotics was generally more effective
      than single drugs, with the regimen netilmicin followed by minocycline at 2 h
      showing the highest antibacterial effect. In the mouse model of pulmonary
      infection, the bacterial counts and histopathological findings of the lungs
      improved by treatment with this regimen. This regimen led also to a significantly
      high survival rate of mice with systemic infection compared to the other
      treatment regimens. Therefore, it was concluded that administration of netilmicin
      followed by minocycline at 2 h may be an effective combination against MRSA
      infection.

PMID- 10075277
TI  - Discrepancies between mecA PCR and conventional tests used for detection of
      methicillin resistant Staphylococcus aureus.
AB  - Conventional and molecular techniques are being used in the detection of
      methicillin resistance in Staphylococcus aureus but they do not always show
      concordant results. In this study, a mecA PCR-based amplification was compared
      with the 1 microg oxacillin disk diffusion test and the Epsilometer test (E-test)
      for detection of MICs. Among 31 isolates initially characterized as MRSA by the
      disk diffusion test, mecA was detected in only 13 (42%) isolates. The E-test
      showed a wide range of oxacillin MICs (0.5 - > 256 microg/ml) among these 31 MRSA
      isolates: seven isolates had an MIC of > 256 microg/ml, one had 64 microg/ml, two
      had 4 microg/ml, two had 3 microg/ml, one had 2.5 microg/ml, nine had 2
      microg/ml, three had 1.5 microg/ml, five had 1 microg/ml and one had 0.5
      microg/ml. Comparing the mecA PCR results with the E-test oxacillin MIC findings
      revealed that mecA was detected in seven of eight isolates (87.5%) with an MIC of
      > or = 64 microg/ml, in three of 14 isolates (21.4%) with an MIC of 2-4 microg/ml
      and in three of nine isolates (33.3%) with an MIC of < 2 microg/ml. Beta
      lactamase production was positive in 28/31 isolates (90.3%). Because of this
      variation between tests and since several resistance mechanisms are known to
      mediate methicillin resistance in S. aureus, the reliable detection of MRSA
      cannot be solely based on detection of mecA gene in S. aureus. At this stage and
      until new guidelines are introduced by an official body, such as NCCLS, a
      combination of conventional methods alone or together with a molecular method
      should be used every time S. aureus is tested for detection of methicillin
      resistance.

PMID- 10075278
TI  - Gradual increase in the minimum inhibitory concentration of penicillin among both
      susceptible and resistant Streptococcus pneumoniae isolates from Greek children
      during 1995-1997.
AB  - A total of 140 non-replicate Streptococcus pneumoniae community isolates from
      Greek children collected during the period 1995-1997 were studied. Combined
      intermediate and high penicillin resistance rates were 23% in 1995, 29% in 1996,
      and 27% in 1997. The proportion of highly resistant isolates steadily increased
      from 2% in 1995 to 12% in 1997. There was no significant difference in penicillin
      resistance rates among colonizing and infecting isolates (23 and 27%,
      respectively). Over the study period, a clear shift towards higher penicillin MIC
      was observed among both the susceptible and resistant groups. Thus, penicillin
      resistance rates were equally high among colonizing and infecting isolates and
      resistance levels appeared to be gradually increasing throughout the entire S.
      pneumoniae population.

PMID- 10075279
TI  - The effect of new disinfectant substances on the metabolism of Enterobacter
      cloacae.
AB  - The antimicrobial mechanism of 16 new commercially manufactured disinfectant
      substances on an Enterobacter cloacae strain was studied. The substances tested
      represent 11 quaternary ammonium salts (QAS) and five combinated QAS with other
      ingredients. The antimicrobial efficacy was characterized by influencing the
      growth of bacterial cells expressed by MIC and ED50 values as well as by the
      inhibition of the incorporation rate of [14C] adenine and [14C] leucine. The
      disinfectants are divided into three groups according to their efficacy. The
      first group comprised substances with strong inhibitory effect (MIC 0.006-0.048
      mg l(-1)) such as triquart, topax 91, benzalkonium chloride, neoquat S, ID 213,
      and antibacteric P. The second group represented substances with good
      antibacterial efficacy (MIC 0.048-0.15 mg l(-1)), and the third group were
      substances with MIC values up to 0.195-0.39 mg l(-1). Cetrimide had low activity
      (MIC 3.12-6.25 mg l(-1)). The effect of substances studied on the biosynthetic
      processes expressed by R values (IC50 Ade:IC50 Leu) showed that these values were
      < 1 except ADL 007. Much lower IC50 Ade and IC50 Leu values of the disinfectant
      substances studied suggested interference of these substances with nucleic acid
      synthesis and proteins synthesis which was expressed by inhibition of both
      precursors. All substances except cetrimide caused an inhibition of the
      endogenous respiration. The highest inhibition was caused by benzalkonium
      chloride. This affected the respiration significantly in the presence of
      intermediators of the Krebs' cycle (glycerol, aspartate). The tested substance
      suppressed the growth of E. cloacae probably through interference with energy
      yielding and energy-requiring processes of the cells.

PMID- 10075280
TI  - Characterization of antimicrobial agents extracted from Asterina pectinifera.
AB  - The extracts from the starfish Asterina pectinifera obtained using various
      organic solvents and distilled water were tested for their antimicrobial
      activities against fungi and yeasts. The methanol and water extracts were found
      to be the most active and Aspergillus spp. and Cryptococcus neoformans proved to
      be sensitive species. The extracts are polar, stable to a wide range of pH and a
      high temperature, and possess a very distinctive UV spectrum. The colour
      reactions for functional groups of antimicrobial substances indicate the presence
      of some distinctive chemical properties common to steroidal oligoglycosides which
      results suggest that the antimicrobial activity is due to structures common to
      steroidal oligoglycosides.

PMID- 10075281
TI  - Effects of Yokuinin on the therapeutic efficacy of a new benzoxazinorifamycin KRM
      1648 against Mycobacterium avium infection.
AB  - The Chinese traditional medicine, Yokuinin, which has anti-inflammatory effects
      and anti-human papilloma virus activity, was examined for its effects on the
      therapeutic efficacy of a benzoxazinorifamycin KRM-1648 (KRM) against
      Myobacterium avium infection in mice. Reverse transcription-PCR analysis revealed
      that Yokuinin increased the mRNA expression of all test cytokines in lung tissues
      of infected ice at week 8, in the order transforming growth factor-beta (TGF
      beta) > IFN-gamma > TNF-alpha > IL-10. Mice given Yokuinin in combination with
      KRM had higher levels of TFG-beta mRNA expression than did mice given KRM alone,
      indicating that TGF-beta plays an important role in the expression of the anti
      inflammatory effect of Yokuinin in vivo. Yokuinin reduced IL-10 production by M.
      avium-infected macrophages ph. (M phis) but did not affect M phi TFG-beta
      production. Although Yokuinin significantly modified cytokine expression in M.
      avium-infected mice, this drug did not influence the therapeutic efficacy of KRM
      against M. avium infection, suggesting that administration of Yokuinin in
      combination with KRM to the patients with M. avium infection does not cause
      severe disadvantages.

PMID- 10075282
TI  - HPLC determination of clofazimine in tissues and serum of mice after intravenous
      administration of nanocrystalline or liposomal formulations.
AB  - A simple HPLC method is described for the determination of clofazimine in mouse
      tissues and in serum. The main application of the method was the determination of
      the drug in mouse tissues after i.v. administration of nanocrystalline
      suspensions or liposomal encapsulated clofazimine. Tissues were extracted with a
      10-fold (w/v) volume of an extraction solution consisting of methanol/glacial
      acetic acid 9:1 (v/v). Serum proteins were precipitated with a 2-fold volume of
      acetonitrile. Isocratic chromatography was performed using an anion exchange
      column (Nucleosil 100-5 SA, Macherey & Nagel) for separation. The mobile phase
      was a mixture of acetonitrile and 0.1 mol/l aqueous phosphoric acid (75:25, v/v),
      adjusted to pH 2.9 with sodium hydroxide solution. Absorption of the eluate was
      monitored at 495 nm. The assay was precise, simple to perform and fast. Recovery
      from tissues was > or = 98%, from nanoparticles > or = 98%, and from liposomes >
      or = 96%. No interference was observed in extracts from mouse liver, spleen,
      lungs and human serum.

PMID- 10075283
TI  - Influence of fever on the pharmacokinetics of ciprofloxacin.
AB  - The influence of fever on the pharmacokinetics of ciprofloxacin was investigated
      in seven patients with acute febrile diseases. Antibiotic serum concentrations
      were determined using high-performance liquid chromatograpy (HPLC). The analog
      computer and the Simulink software package were used to identify the
      pharmacokinetic model and Penoclin software package to obtain the secondary
      parameters. During fever, higher maximum serum concentrations (Cmax) of
      ciprofloxacin were observed in six out of seven patients. The result suggests
      that the influence of fever on the pharmacodynamics of ciprofloxacin is
      favorable.

PMID- 10075284
TI  - Preliminary analysis of a multicenter clinical trial using Multiload Cu 375SL for
      emergency contraception.
AB  - OBJECTIVE: To evaluate the efficacy, side-effects and acceptability of the
      Multiload Cu 375SL (MLCu 375SL IUD) used as emergency contraception (EC). METHOD:
      Women who requested EC had a MLCu 375SL IUD inserted within 5 days after
      unprotected intercourse. RESULTS: Data from 515 subjects who completed the follow
      up visits were analyzed. The majority were parous women (428, 83.1%). Most of the
      nulliparous women, 70 out of 87 (80.5%), had had a previous abortion. The
      efficacy rate was 92.40%. Two pregnancies were detected at the follow-up visits.
      One of them was considered to be a user failure. There were no failures in
      insertion procedure or no pelvic infections in either group. The common
      complaints were pain and bleeding. The removal rate in the nulliparous group
      (14.9%) was significantly higher than in the parous group (3.5%). CONCLUSIONS:
      Insertion of a MLCu 375SL IUD within 5 days after unprotected intercourse
      provides an alternative emergency contraceptive method. It is more acceptable to
      parous women who plan to continue practicing contraception. It is important to
      provide careful counselling to clients and to emphasize that the insertion of the
      IUD must be within 5 days after unprotected intercourse in order to reduce the
      potential risk of pregnancy.

PMID- 10075285
TI  - Emergency contraception: the user profile.
AB  - Emergency contraception (EC) has recently become available, accepted and widely
      used in Sweden but little is known about the characteristics and background
      factors of women requesting EC. METHODS: During a four-month period, consecutive
      women (n = 762) visiting family planning clinics to request emergency
      contraception filled out a questionnaire about their current need for EC.
      RESULTS: The user of emergency contraception was typically a nulligravid young
      woman (83%) but 13% had a previous history of at least one induced abortion and
      41% had given birth in the past. One out of four had used EC before, and of these
      20% more than once. Condom breakage was the major reason for the current need for
      EC but as many as 37% had not discussed the need for contraception prior to
      intercourse. Friends were the most important source of knowledge about EC.
      CONCLUSION: Women requesting emergency contraception could be anyone and
      emergency contraception is used to compensate for contraceptive failure in order
      to prevent unwanted pregnancies.

PMID- 10075286
TI  - Family planning camps as an opportunity to assess and help reduce the prevalence
      of reproductive health morbidities in rural Nepal.

PMID- 10075287
TI  - Weight variation in users of the once-a-month injectable contraceptive Cyclofem.
AB  - This study was aimed to evaluate weight variation in 3183 women using the
      injectable contraceptive Cyclofem. All women were allocated to groups according
      to their weight at admission. The weight gain was inversely proportional to the
      weight at admission. The groups of women weighing less than 50 kg at admission,
      experienced a higher increase, 2.8% in four months, and they continued gaining
      weight, reaching 7.7% in 13 months. Women weighing more than 64 kg at admission
      did not present any weight change in 4 months and increased only 1.7% at 13
      months. When women were classifed as discontinuers due to weight increase,
      discontinuers due to other reasons, and continuers, at four months, the
      differences in the mean weight between the groups was statistically significant
      only in the groups weighing 55 kg or more at admission. At 13 months, the results
      were similar and the differences were statistically significant only in the
      groups weighing 55-59 kg and 60-64 kg. Discontinuation rates due to weight
      increase were proportional to the weight at admission. This rate was almost three
      times higher in the group of women weighing more than 64 kg at admission than in
      the group weighing less than 55 kg (p<0.001). In conclusion, considering the data
      presented in this study, it is impossible to recommend health providers to inform
      women who choose Cyclofem as their contraceptive method, that this method may
      increase their weight throughout its use.

PMID- 10075288
TI  - User acceptability of a female condom (Reality) in Shanghai.
AB  - Thirty married couples evaluated the Reality female condom on questionnaires
      about its acceptability for 300 acts of coitus (10 per couple). An analysis of
      the summary questionnaires showed: 90% of couples considered the female condom an
      acceptable method and 87% felt it was a good contraceptive device; the majority
      of couples (87%) found it easy to use; and 80% of females and 73% of males
      reported that, in comparison with the male condom, the effect on sexual pleasure
      was either improved or no different. A little more than half of the couples (55%)
      preferred it to male condoms. To look at the learning curve effect, an additional
      analysis was completed by pooling the first 5 applications of each user and
      comparing the results with the pooled results of the second 5 uses. All the
      findings suggest that a certain proportion of couples of childbearing age will
      choose the Reality female condom for contraception if it enters into the Chinese
      market. As a new contraceptive barrier device, the female condom may require a
      certain amount of education and awareness before it will be fully recognized as
      an important option to help prevent pregnancy as well as sexually transmitted
      infections.

PMID- 10075289
TI  - Results of an efficacy-finding study (EFS) with the computer-thermometer
      Cyclotest 2 plus containing 207 cycles.
AB  - Prospectively collected cycles of 207 women were used to find out the efficacy of
      the Cyclotest 2 plus algorithm in detecting the fertile time in a woman's cycle.
      The results of the device were compared with the beginning and the end of the
      fertile time identified by the symptothermal method (STM) of natural family
      planning (NFP). It was found that the algorithm led to dangerous reduction of the
      fertile time (FT) in only 2 out of 207 woman cycles (0.96%). However, at the end
      of fertile time (FE) the device requested more abstinence than was necessary in
      about 12% of the cycles. We feel that more research should be performed on
      detecting the end of the fertile time.

PMID- 10075290
TI  - Anterior-retroperitoneal living donor nephrectomy: technique and outcomes.
AB  - Of 133 consecutive renal transplants, 61 (46%) were living donor grafts recovered
      in an anterior-retroperitoneal approach. Donor demographics, operative-anesthetic
      care, length of stay (LOS), hospital charges, and complications were reviewed
      with donor and recipient follow-up of 4 to 40 months. Donors included 35 women
      and 26 men, ages 22 to 61 years (mean, 42.2); thirty-nine were living related and
      22 were living unrelated donors. Pretransplant evaluation defined renal anatomy
      and function (minimal creatinine clearance, 75 cc/minute). Hospital admission
      occurred the morning of donation. Nephrectomy by the anterior-retroperitoneal
      approach (no rib resection) was followed by postoperative epidural pain control,
      early resumption of diet, progressive ambulation, and aggressive pulmonary care.
      Operating room time door-to-door averaged 2 hours, 43 minutes (range, 1 hour, 45
      minutes-3 hours, 55 minutes). Donors were hospitalized for 2 (n = 7), 3 (n = 24),
      4 (n = 19), and 5 to 8 (n = 11) days (mean LOS, 3.75; range, 2-8 days). The mean
      charge for donor hospitalization was $15,329 (range, $10,808-$29,579). One donor
      required transfusion; another was readmitted for wound drainage and pneumonia
      treated medically. All donors remain well with normal renal function. One early
      graft loss (3 days) occurred from arterial intimal dissection; all others gained
      life-sustaining function. Recipient (98%) and graft (92%) survival was excellent
      at 4 to 40 months. Anterior-retroperitoneal living donor nephrectomy is safe and
      effective, permitting hospital LOS of usually <4 days, early recovery, and no
      lasting complications. Excellent donor and recipient results from this procedure
      should compel critical assessment of techniques requiring more extensive
      operative exposure or more costly operating room and hospital approaches to donor
      surgical management.

PMID- 10075291
TI  - Efficacy of routine preoperative computed tomography scans in colon cancer.
AB  - A retrospective review of 180 patients who underwent surgery for primary colon
      carcinoma from August 1989 to August 1994 was performed to evaluate the necessity
      of preoperative CT scans in patients with known colon cancer. Sixty-seven
      patients had preoperative CT scans. Data were collected to evaluate the ability
      of the scan to detect hepatic metastases, lymph node involvement, and incidental
      findings that would possibly alter the planned surgical approach. In this study,
      CT had a sensitivity and specificity of 75 per cent and 88 per cent,
      respectively, in detecting hepatic metastases. Only 19 per cent of patients with
      lymph node involvement were correctly staged with CT scans as having
      lymphadenopathy. Only 3 of 67 patients had incidental findings on CT scans that
      ultimately changed the surgical approach. It is apparent that because CT scans
      detect only 75 per cent of hepatic and 19 per cent of hepatic and lymph node
      involvement and does not seem to alter the planned approach, it is not justified
      for routine preoperative evaluation of all patients. We, therefore, recommend a
      more selective approach to patients suspected of having advanced disease if the
      surgeon suspects that the information may alter the surgical approach.

PMID- 10075292
TI  - Breast cancer and HIV: what do we know?
AB  - The present acquired human immunodeficiency syndrome-defining neoplasms are
      Kaposi's sarcoma, non-Hodgkins lymphoma, and cervical cancer. However, other
      malignancies have recently been associated with human immunodeficiency virus
      (HIV) infection. Is there also a link between breast cancer and HIV infection?
      Breast cancer seems to be more aggressive in the setting of immunocompromise by
      HIV infection, as demonstrated by the clinical course of two patients recently
      treated at this institution and review of the available literature. As the
      acquired human immunodeficiency syndrome epidemic affects increasing numbers of
      women and survival improves, surgeons will be frequently called on to diagnose
      and treat breast cancer in the HIV+ patient.

PMID- 10075293
TI  - Laparoscopic choledochoduodenostomy.
AB  - Laparoscopic cholecystectomy has become the gold standard for treatment of
      patients with symptomatic cholelithiasis. Management of common bile duct stones
      in the era of laparoscopy is an area of controversy. Although perioperative
      endoscopic retrograde cholangiography remains as a widely used procedure,
      experience is accumulating on the exploration of the common bile duct with the
      laparoscope. A biliary drainage procedure is indicated in selected patients with
      choledocholithiasis. Initially described by Reidel in 1892, side-to-side
      choledochoduodenostomy has become a popular biliary-enteric anastomosis technique
      in the last century. We describe two patients with recurrent choledocholithiasis
      and biliary obstruction due to benign biliary strictures. Both patients underwent
      laparoscopic common bile duct exploration and stone extraction. A side-to-side
      choledochoduodenostomy is then performed laparoscopically as a drainage
      procedure. Laparoscopic choledochoduodenostomy resulted in resolution of jaundice
      and relief of biliary obstruction. Laparoscopic choledochoduodenostomy can be an
      acceptable alternative to the open choledochoduodenostomy. In addition to a
      tension-free anastomosis and an adequate-sized stoma, intracorporeal suturing and
      knot-tying skills are also essential to the success of this procedure.

PMID- 10075294
TI  - Initial resuscitation volume in uncontrolled hemorrhage: effects on organ
      function.
AB  - Conventional resuscitation of hypovolemia due to hemorrhage has consisted of
      aggressive fluid administration. Recent studies have suggested that surgical
      control of bleeding before fluid resuscitation might improve early survival. The
      effects of limited resuscitation on organ function have not been assessed in
      these studies. We developed a model of moderate intraperitoneal hemorrhage
      designed to evaluate long-term end-organ function after various resuscitation
      protocols. Male Sprague-Dawley rats underwent ketamine anesthesia, followed by
      placement of femoral artery and vein lines. Intraperitoneal hemorrhage was
      induced by division of distal branches of the ileocolic artery and vein. After 5
      minutes of bleeding, the animals were randomized to one of three resuscitation
      groups: Group 1 received no fluid resuscitation before surgical control of the
      hemorrhage; Group 2 received 0.5 mL of lactated Ringer's solution (LR) every 5
      minutes for a mean arterial pressure (MAP) of less than 80 mm Hg; Group 3
      received 2.0 mL of LR every 5 minutes for a MAP of less than 80 mm Hg. In all
      three groups, after 20 minutes, the bleeding was surgically controlled. All rats
      were then resuscitated with LR to a MAP of 80 mm Hg. The intravascular lines were
      removed, and the rats were allowed to recover from anesthesia and were returned
      to animal holding. On the 7th day, survivors were sacrificed, and their blood was
      assayed for hematocrit and serum levels of bilirubin, alanine aminotransferase,
      urea nitrogen, and creatinine. Kidneys, lungs, and liver were harvested for
      microscopic examination. Survival was lower in Group 2 than in the other groups
      (90%, 60%, and 100%, respectively; P = 0.04), but all deaths occurred within 3
      hours of hemorrhage and were due to either hypovolemia or anesthetic
      complications. No histologic abnormalities were identified in the livers of the
      animals that survived, but pulmonary atelectasis and mild-to-moderate renal
      tubular necrosis were identified uniformly. No histologic differences could be
      discerned between the groups. Hematocrit and indices of liver and renal function
      were similar in all groups, and no animal developed organ dysfunction. In this
      model of moderate uncontrolled intraperitoneal hemorrhage, the volume of fluid
      resuscitation, or the absence of resuscitation, had an inconsistent effect of 7
      day survival and did not influence function or histologic appearance of the
      liver, lungs, or kidneys 7 days after hemorrhage.

PMID- 10075295
TI  - Metastasis of hepatocellular carcinoma to the right colon manifested by
      gastrointestinal bleeding.
AB  - An 82-year-old black woman with a history of hepatocellular carcinoma presented
      with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm
      polypoid mass at the level of the ascending colon with evidence of active
      bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular
      carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor,
      and the patient underwent an ileocolectomy. The serosal side of the colonic
      lesion was free from tumor, and there was no peritoneal implantation, direct
      extension, or lymph node involvement. This case represents an extremely rare
      presentation of metastatic hepatocellular carcinoma.

PMID- 10075296
TI  - Perforated peptic ulcer following gastric bypass for obesity.
AB  - Peptic ulcer in the excluded segment of a gastric bypass performed in the
      management of morbid obesity has only rarely been reported in the literature. The
      purpose of this study is to review our experience with the condition in a series
      of 4300 patients who underwent gastric-restrictive surgery between 1978 and 1997.
      Eleven patients presented with acute perforation of a peptic ulcer in the
      excluded gastric segment. Nine ulcers were duodenal, one was gastric, and one
      patient had both gastric and duodenal perforations. The time between primary
      gastric-restrictive surgery and ulcer perforation varied from 20 days to 12
      years. All patients presented with upper abdominal pain. The classical
      radiological sign of perforated peptic ulcer, free air under the diaphragm, did
      not occur in any patient. Nine patients were initially treated by primary closure
      of the perforation with subsequent definitive ulcer therapy by vagotomy,
      pyloroplasty, or gastrectomy. One case, initially treated elsewhere, was managed
      by placement of a Malecot catheter through the duodenal perforation, gastrostomy,
      and peritoneal drainage. One recent case remains symptom-free on H2 blockers
      after simple closure. There was no mortality. Six cases were previously reported
      in the literature with a 33 per cent mortality rate.

PMID- 10075297
TI  - The absent role of prophylactic antibiotics in low-risk patients undergoing
      laparoscopic cholecystectomy.
AB  - A retrospective chart review was done to determine the infection rate and the use
      of prophylactic antibiotics in consecutive laparoscopic cholecystectomies done in
      a single community. Incisional infections were discovered in 11 of 566 cases, 10
      of whom had received prophylactic antibiotics. The infected patients were
      significantly older, had longer procedures, and had more comorbidity than the
      uninfected patients. They were also more likely to have a palpable mass
      preoperatively and past biliary surgery. A second, prospective study was done to
      evaluate the efficacy of the use of antibiotic prophylaxis in low-risk patients.
      Fifty-three patients were randomized into two double-blinded groups. No
      incisional infections occurred in either group within 30 days postoperatively.
      This suggests prophylactic antibiotics are not needed to prevent infections for
      low-risk patients undergoing laparoscopic cholecystectomy.

PMID- 10075298
TI  - An alternative approach: antegrade catheter-directed thrombolysis in a case of
      phlegmasia cerulea dolens.
AB  - Phlegmasia cerulea dolens is an uncommon sequela of severe deep venous thrombosis
      of the lower extremities. Characterized by massive edema, arterial and venous
      compromise, and threats to limb and life, this clinical entity is a clear
      indication for thrombolytic therapy. We report an innovative approach to
      conventional thrombolysis via a lesser saphenous vein cut-down. This simple
      technique is a safe, reliable alternative to present methods of achieving deep
      venous access. Hence, it should be considered as an addition to the treatment
      armamentarium for massive deep venous thrombosis of the lower extremity.

PMID- 10075299
TI  - Descending thoracic aortobifemoral bypass: an alternative approach for difficult
      aortic revascularization.
AB  - Descending thoracic aortobifemoral bypass is an alternative inflow operation in
      cases in which standard aortobifemoral or axillobifemoral bypass is not an
      option. We performed descending thoracic aortobifemoral bypass for failed inflow
      operations in four patients, prior abdominal/pelvic radiation in two patients,
      poor quality distal aorta (extensive atherosclerotic disease or poor tissue
      quality) in two patients, and abdominal sepsis in two patients. Eight have had
      excellent results with patency at a mean follow-up of 38 months. There was no
      limb loss. One patient died of organ failure, and one patient with
      hypercoagulability developed a graft clot. A literature review disclosed that a
      descending thoracic aortobifemoral bypass was reported to have been performed in
      203 patients, with most cases reported in the last decade. This procedure was the
      primary inflow operation in 42 per cent of cases. Indications for the operation
      included failed aortic grafts (38%), "hostile" abdomen (21%), infected aortic
      grafts (18%), and other (23%). The patency rate was 95 per cent at 6 months. Few
      long-term results are known, but the results appear to be durable. Descending
      thoracic aortobifemoral bypass is a useful operation in highly selected
      circumstances in which conventional methods of aortic reconstruction are not
      available.

PMID- 10075300
TI  - Malignant eccrine spiradenoma: a previously unreported presentation and review of
      the literature.
AB  - Malignant eccrine spiradenomas (MESs) are rare tumors arising from previously
      benign eccrine spiradenomas. A review of the literature reveals only 25 published
      reports of malignancy arising from eccrine spiradenoma and no prior reports of an
      MES of the scalp. The tumors have a metastasis rate of >50 per cent in reported
      cases with high resultant mortality rates. We present the first case report of a
      single MES of the scalp. Multiple resections were required for local control.
      Both magnetic resonance imaging and lymphoscintigraphy were used to assess
      regional spread. A review of the literature follows to include histopathology,
      diagnosis, and both surgical and adjuvant therapeutic options.

PMID- 10075301
TI  - Preoperative chemoradiotherapy in the treatment of gallbladder cancer.
AB  - Gallbladder cancer is generally associated with a poor prognosis, with local
      recurrence being the main pattern of failure. In an attempt to improve on the
      present status of management, we evaluated a prospective Phase II study involving
      preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a
      potentially resectable gallbladder cancer detected after cholecystectomy, 18 were
      treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week)
      concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5
      and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7
      patients). Delay in surgery due to hematological toxicity was seen in 6 patients.
      Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13
      (86%). Pathologic findings after reoperation revealed residual tumor in both
      liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7
      patients are alive. Among the patients who died after curative resection, local
      recurrence was demonstrated in only 1. This is the first report concerning
      preoperative chemoradiation in gallbladder cancer. To assess its effect on
      survival, a prospective randomized trial will be necessary.

PMID- 10075302
TI  - Secure placement of continuous ambulatory peritoneal dialysis catheters under
      laparoscopic assistance.
AB  - Laparoscopic surgical procedures were performed in 18 patients with end-stage
      renal disease for the placement of a Tenckhoff peritoneal dialysis catheter.
      Among them, 6 patients had received previous lower abdominal surgical treatment
      and 3 patients underwent laparoscopic rescue of dysfunctional Tenckhoff
      catheters. The operating time was between 40 and 80 minutes (median, 50 minutes).
      After a median follow-up period of 11 months, the short-term results revealed
      that no significant morbidity was associated with this procedure, and all
      catheters except two functioned well postoperatively. One of the catheters was
      not functional because of the patient's death, and the other one was removed
      because of persistent peritonitis. Laparoscopic secure placement of continuous
      ambulatory peritoneal dialysis catheters appears to be a simple, safe, and viable
      procedure, even in patients with previous lower-abdominal operations. The same
      technique can be used to rescue dysfunctional catheters that are displaced or
      obstructed by adhesion and omental wrapping, thus increasing catheter longevity.

PMID- 10075303
TI  - Unilateral male breast masses: cancer risk and their evaluation and management.
AB  - Breast cancer is an uncommon cause of breast enlargement in the adult male.
      Overall, it accounts for <1 per cent of all male cancers. Although most male
      breast carcinomas are clinically apparent, distinguishing early breast cancer
      from gynecomastia, the most common cause of male breast enlargement, is
      considered a difficult task. To overcome this difficulty, many surgeons proceed
      directly to surgery as their initial diagnostic test. Although appropriate in
      some cases, the infrequent occurrence of male breast cancer and the diagnostic
      accuracy of mammography and fine-needle aspiration cytology suggest a
      modification of our present management. The aim of this study was to assess the
      incidence of breast cancer in men with unilateral breast masses and to propose a
      treatment algorithm for unilateral male breast masses. The medical records of 36
      male patients who underwent subcutaneous mastectomy for a unilateral breast mass
      at the Buffalo Veterans Administration Medical Center between 1989 and 1996 were
      retrospectively reviewed. Data was collected on a standard data form. The median
      age was 63-years-old (range, 22-82). Gynecomastia was diagnosed in 30 patients
      (83%), lipoma in 4 patients (11%), invasive breast cancer in 1 patient (3%), and
      melanoma in situ in 1 patient (3%). Of the 30 patients with gynecomastia, 60% (18
      patients) gave a history of a medical condition or use of medications known to
      cause gynecomastia, compared with 16 per cent (1 of 6) of the patients without
      gynecomastia (P = 0.08). Half of the patients with gynecomastia presented with an
      asymptomatic mass compared with 67 per cent of the patients without gynecomastia
      (P = not significant). The median duration of symptoms for patients with
      gynecomastia was 3 months. Men with unilateral breast masses have a low incidence
      of breast cancer. A male patient with a palpable unilateral breast mass
      consistent with gynecomastia on the basis of historical, physical and
      mammographic findings does not require surgical biopsy unless other clinical
      indications prevail. Lack of symptoms (pain) related to the mass is probably not
      helpful in deciphering gynecomastia from breast cancer.

PMID- 10075304
TI  - The occult pneumothorax: an increasing diagnostic entity in trauma.
AB  - The increasing use of CT for the evaluation of blunt abdominal trauma has
      diagnosed undetected pneumothoraces in many patients. We performed a
      retrospective study at a major trauma center to determine the incidence of occult
      pneumothorax in the trauma patient. All trauma patients (3121) admitted to a
      Level I trauma center over a 51-month period were reviewed to determine the
      incidence of pneumothorax and occult pneumothorax, the method of diagnosis, and
      treatment. All major trauma patients received a chest X-ray (CXR), whereas 842
      patients (27%) underwent an abdominal CT scan. In the 172 patients diagnosed with
      pneumothorax, 157 abdominal CT scans were performed and 143 were positive for
      pneumothorax. CXR revealed 49 right-sided pneumothoraces and 58 left-sided
      pneumothoraces in 95 patients. Abdominal CT scans diagnosed 73 right
      pneumothoraces and 90 left pneumothoraces in 143 patients. There were 67 patients
      (71 thoraces) who were seen to have a pneumothorax on abdominal CT scan not seen
      on admission CXR. This represents 2.2 per cent of all trauma patients and 7.9 per
      cent of patients with abdominal CT scans. In looking at just trauma patients with
      pneumothorax, the CT scan was responsible for diagnosing 39 per cent of the
      patients with a pneumothorax. The occult pneumothorax is being diagnosed more
      frequently as methods of evaluating and diagnosing trauma patients become more
      sensitive.

PMID- 10075305
TI  - Laparoscopic procedures in pregnancy.
AB  - As the applications of laparoscopy for general surgical procedures expanded in
      the 1990s, pregnancy was initially considered a contraindication. Several case
      reports have suggested the safety of laparoscopy in pregnancy. Previous clinical
      studies indicate a higher fetal mortality may exist and advised caution. To
      evaluate the fetal outcome of laparoscopic procedures in pregnant patients at our
      institution, we retrospectively reviewed the medical records between 1991 and
      1997 and identified 21 pregnant patients who underwent either a laparoscopic (n =
      12) or open (n = 9) procedure. Appendectomies, cholecystectomies, and diagnostic
      laparoscopies were performed. Specific variables including age, length of
      procedure, hospital stay, duration of parenteral analgesic use, gestational age
      at the time of surgery and delivery, O2 saturation and EtCO2 during surgery,
      APGAR scores, and birth weights were compared between the two groups.
      Laparoscopic procedures during pregnancy resulted in shorter hospital stays (34
      hours versus 91 hours; P = 0.01), less use of parenteral narcotic analgesics (5
      hours versus 29 hours; P = 0.05), and no prolongation of operative times (51
      minutes versus 63 minutes; P = 0.20). In addition, laparoscopy was performed at
      earlier gestational ages (12 weeks versus 29 weeks; P = 0.001). There was one
      miscarriage 7 days after a laparoscopic cholecystectomy early in the 1st
      trimester that was not statistically significant. Our experience did not show a
      higher incidence of fetal loss when comparing laparoscopic to open procedures in
      pregnant patients.

PMID- 10075306
TI  - Laparoscopic management of mesenteric cyst.
AB  - Mesenteric cysts are rare intra-abdominal tumors. Most are found during
      laparotomy for other reasons. The symptoms are often vague and minimal. CT of the
      abdomen gives the most information and is the diagnostic method of choice. The
      preferred treatment for mesenteric cysts is complete resection at laparotomy.
      However, the advancement of minimal-access surgery has allowed laparoscopic
      excision as a safe and advantageous approach with minimal morbidity and shorter
      hospital stay and recovery time for the patient.

PMID- 10075307
TI  - Colostomy closure: impact of preoperative risk factors on morbidity.
AB  - The objective of this study was to stratify patients for colostomy closure into
      risk categories according to preoperative variables. This was a retrospective
      case series. Median follow-up was 82 months. A tertiary care academic medical
      center was the setting for this study. A study sample of 155 consecutive patients
      who underwent colostomy closure at a single institution between 1985 and 1995
      were included in this study. The following preoperative variables were analyzed:
      indication for colostomy fashioning; age; gender; American Society of
      Anesthesiology (ASA) class; presence of cardiac, renal, or pulmonary
      dysfunctions; presence of diabetes mellitus; and immunosuppression. The
      occurrence of adverse outcome, as evidenced by postoperative morbidity and
      mortality, was used as the main outcome measure. Complications occurred in 49
      patients (31.6%), including a 1.3 per cent mortality. There was a trend of
      increasing morbidity with increasing ASA class. The single factor that showed a
      statistically significant increase in morbidity was the presence of diabetes (P =
      0.036). Predicted probabilities of complications for patients with ASA III with
      renal disease was 31 per cent, increased to 47.9 per cent if cardiac disease was
      also present and to 77 per cent with the addition of diabetes. The presence of
      diabetes carries an independent risk factor for adverse outcome in colostomy
      closure. This study provides information about stratification of postoperative
      risk based on commonly available preoperative variables. In the majority of
      cases, colostomy closure seems to carry a very acceptable complication rate. In
      selected patients with multiple preoperative risk factors, the morbidity becomes
      significantly higher.

PMID- 10075308
TI  - Current clinical concepts in perioperative anticoagulation.
AB  - Management of patients with significant risks for thromboembolism in the
      perioperative period requires consideration of both risks of thromboembolism and
      risks of anticoagulant therapy. Patients who are receiving warfarin therapy
      because of recent venous thromboembolism, nonvalvular atrial fibrillation, and
      mechanical heart valves are at increased risk during the interval when the
      warfarin is discontinued and when the international normalized ratio is at a
      subtherapeutic level. In patients with an acute venous thromboembolic event
      within the past month, the use of intravenous heparin appears to be justified
      both preoperatively and postoperatively. If the venous thromboembolic event was
      within the past 2 to 3 months, use of intravenous heparin appears justified in
      the postoperative period. More than 3 months after an acute episode of venous
      thrombophlebitis, the relatively low risk of recurrence does not appear to
      justify the risks of complications from intravenous heparin. Patients with
      increased risks of arterial embolism, specifically those with nonvalvular atrial
      fibrillation and mechanical heart valves, are generally not at sufficient risk of
      arterial embolism to justify use of intravenous heparin during the perioperative
      subtherapeutic international normalized ratio interval when warfarin is withheld.
      A potential increased risk of recurrent arterial embolism when the preceding
      event was within a month suggests that elective surgery should be deferred beyond
      a month whenever possible in such patients. The use of fixed-dose, subcutaneous
      low molecular weight heparin has been observed to have advantages over use of
      unfractionated intravenous heparin both in terms of safety and efficiency.
      Further refinements in management of patients with significant risks of
      thromboembolism may occur with increased experience with low molecular weight
      heparin.

PMID- 10075309
TI  - Comparison of antiadhesive treatments using an objective rat model.
AB  - Intraperitoneal adhesions are a significant problem (increased morbidity,
      mortality, and cost) for patients undergoing abdominal procedures. Although a
      variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or
      barrier/separation methods) have been used with some success in preventing
      adhesions, a comparison of these different modalities has yet to be performed in
      a model that objectively measures intraperitoneal adhesion formation. Our
      objectives were to establish an objective, reproducible model of intraperitoneal
      adhesion formation and to establish efficacy of different treatment modalities in
      decreasing the strength and extent of intraperitoneal adhesions. In this two-part
      study, a rat model establishing an objective measure of both the strength and
      extent of intraperitoneal adhesions was used to compare different treatment
      modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA),
      streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and
      tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and
      sodium hyaluronate] and a control group were compared in the first phase. In the
      second phase, the two most successful agents (rtPA, CMC) were compared both alone
      and in combination against a commercially available barrier agent (Seprafilm) and
      a control group. In the first phase of the study, rtPA was the only agent that
      had a statistically significant effect in decreasing the strength of adhesions.
      CMC was the only agent that demonstrated a decrease in the extent of adhesions,
      and the difference tended toward significance. In the second phase, the
      combination of rtPA and CMC showed a significant decrease in both the strength
      and extent of adhesions when compared with those of the control group. This
      decrease was also observed in the group treated with Seprafilm, which showed no
      difference from the rtPA + CMC group. We conclude that, in this reproducible
      adhesion model, only the combination of rtPA + CMC and Seprafilm significantly
      reduced both the strength and the extent of intraperitoneal adhesions.

PMID- 10075310
TI  - Needle-localized breast biopsy for mammographic abnormalities: a community
      hospital experience.
AB  - Increased awareness of benefits of early detection of breast cancer has resulted
      in increased numbers of screening mammographies and breast biopsies for
      nonpalpable lesions. Tertiary hospital studies have demonstrated positive biopsy
      rates from abnormal mammographic findings at 18 to 32 per cent. We examined the
      effectiveness of needle biopsy for nonpalpable radiographic abnormalities in our
      community hospital. We reviewed 167 records of patients biopsied over a 2-year
      period. Mammographic assessment, biopsy, and pathological assessment were
      performed using accepted methods. Malignancy was detected in 34 of 167 biopsies
      (20%). The biopsy yield rate was highest for mammographic findings of spiculated
      or stellate masses (75%, P < 0.01). Most biopsies (83%) were performed because of
      mammographic findings of microcalcifications or circumscribed enlarging
      masses/nodular developing densities for a positive biopsy yield rate of 16 per
      cent. Rates were higher in patients with personal (44%) or family history (30%)
      of breast cancer and in postmenopausal women (30%). These results demonstrate
      that 1) factors such as age, personal or family history of breast cancer, and
      certain mammographic features of breast lesions are associated with high biopsy
      yield rates, and 2) the biopsy yield rate in our community setting is comparable
      to tertiary hospital experience.

PMID- 10075311
TI  - Surgical residents and ultrasound technician accuracy and cost-effectiveness of
      ultrasound in trauma.
AB  - The purpose of this study is 2-fold: 1) to assess the accuracy of the Focused
      Abdominal Sonogram for Trauma (FAST) as an important evaluative tool for the
      trauma victim as compared with other objective testing resources (i.e.,
      computerized axial tomography scan); and 2) to analyze the cost-effectiveness of
      FAST as performed by surgical residents as compared with ultrasound (US)
      technicians. FAST was performed on 650 trauma victims over a period of 12 months.
      Testing was completed in a trauma room of the emergency department by an US
      technician or a trauma surgical resident as determined by the availability of the
      US technician. Hypotensive patients required two FASTs to be completed for
      comparison of results. Persistent difficulty interpreting the FAST required the
      addition of a computerized axial tomography scan to help clarify the results.
      Statistical analysis was performed using chi2 and analysis of variance. False
      positive, false negative, and true positive, true negative, along with the
      accuracy of FAST were calculated as compared with other diagnostic testing. The
      finding indicated that FAST was both specific (99 per cent) and sensitive (68 per
      cent) in the sample used. Of the 650 patients receiving FAST, true negative was
      95 per cent, true positive was 3 per cent as compared with false negative at 1
      per cent, and false positive at 0.5 per cent. US technicians performed 81 per
      cent of the FASTs with an accuracy of 92 per cent. In comparison, surgical
      residents had a 92 per cent rate of accuracy in the remaining 19 per cent of the
      population. The mean accuracy of both was 94 per cent. Furthermore, FAST as
      performed by resident incurred a single fee of $88 for radiological readings as
      compared with $274 for an US technician fee plus the radiological reading fee of
      $88. FAST as performed by surgical residents is more cost-effective than FAST as
      performed by an US technician.

PMID- 10075312
TI  - Roentgen and his ray: an early impact on modern medicine.

PMID- 10075313
TI  - Clinical pathways for general surgeons: acute upper GI bleeding--peptic ulcer.

PMID- 10075314
TI  - Benefits of weight loss in the treatment of obesity.

PMID- 10075315
TI  - Limitations on the adage "eat a variety of foods"?

PMID- 10075316
TI  - Biotin bioavailability and estimated average requirement: why bother?

PMID- 10075317
TI  - The widening spectrum of celiac disease.
AB  - Celiac disease is a permanent intolerance to ingested gluten that results in
      immunologically mediated inflammatory damage to the small-intestinal mucosa.
      Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA
      genes and with other immune disorders, notably juvenile diabetes and thyroid
      disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with
      multiple deficiency states may be less common than more subtle and often
      monosymptomatic presentations of the disease. Diverse problems such as dental
      anomalies, short stature, osteopenic bone disease, lactose intolerance,
      infertility, and nonspecific abdominal pain among many others may be the only
      manifestations of celiac disease. The rate at which celiac disease is diagnosed
      depends on the level of suspicion for the disease. Although diagnosis relies on
      intestinal biopsy findings, serologic tests are useful as screening tools and as
      an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of
      dietary gluten. Gluten-free diets are now readily achievable with appropriate
      professional instruction and community support. Both benign and malignant
      complications of celiac disease occur but these can often be avoided by early
      diagnosis and compliance with a gluten-free diet.

PMID- 10075318
TI  - Report of a National Institutes of Health--Centers for Disease Control and
      Prevention workshop on the feasibility of conducting a randomized clinical trial
      to estimate the long-term health effects of intentional weight loss in obese
      persons.
AB  - A workshop was convened in 1997 by the National Institutes of Health and the
      Centers for Disease Control and Prevention to consider the need for and
      feasibility of conducting a randomized clinical trial to estimate the long-term
      health effects of intentional weight loss in obese persons. Although the benefits
      of weight loss in obese individuals may seem obvious, little information is
      available showing that intentional weight loss improves long-term health
      outcomes. Observational studies may be unable to provide convincing answers about
      the magnitude and direction of the health effects of intentional weight loss.
      Workshop participants agreed that a well-designed randomized clinical trial could
      answer several questions necessary for developing a rational clinical and public
      health policy for treating obesity. Such information will ultimately provide
      needed guidance on the risks and benefits of weight loss to health care providers
      and payers, as well as to millions of obese Americans.

PMID- 10075319
TI  - Cardiorespiratory fitness, body composition, and all-cause and cardiovascular
      disease mortality in men.
AB  - BACKGROUND: Cardiorespiratory fitness and body fatness are both related to
      health, but their interrelation to all-cause and cardiovascular disease (CVD)
      mortality is unknown. OBJECTIVE: We examined the health benefits of leanness and
      the hazards of obesity while simultaneously considering cardiorespiratory
      fitness. DESIGN: This was an observational cohort study. We followed 21925 men,
      aged 30-83 y, who had a body-composition assessment and a maximal treadmill
      exercise test. There were 428 deaths (144 from CVD, 143 from cancer, and 141 from
      other causes) in an average of 8 y of follow-up (176742 man-years). RESULTS:
      After adjustment for age, examination year, cigarette smoking, alcohol intake,
      and parental history of ischemic heart disease, unfit (low cardiorespiratory
      fitness as determined by maximal exercise testing), lean men had double the risk
      of all-cause mortality of fit, lean men (relative risk: 2.07; 95% CI: 1.16, 3.69;
      P = 0.01). Unfit, lean men also had a higher risk of all-cause and CVD mortality
      than did men who were fit and obese. We observed similar results for fat and fat
      free mass in relation to mortality. Unfit men had a higher risk of all-cause and
      CVD mortality than did fit men in all fat and fat-free mass categories.
      Similarly, unfit men with low waist girths (<87 cm) had greater risk of all-cause
      mortality than did fit men with high waist girths (> or =99 cm). CONCLUSIONS: The
      health benefits of leanness are limited to fit men, and being fit may reduce the
      hazards of obesity.

PMID- 10075320
TI  - Racial differences in amounts of visceral adipose tissue in young adults: the
      CARDIA (Coronary Artery Risk Development in Young Adults) study.
AB  - BACKGROUND: In several white populations, visceral adipose tissue (VAT) is a risk
      factor for development of type 2 diabetes and dyslipidemia. VAT can be accurately
      assessed by computed topography or magnetic resonance imaging, but is also
      estimated from anthropometric variables, such as waist-to-hip ratio, waist
      circumference, or sagittal diameter. To date, anthropometric variables have been
      used largely in whites and inadequate data are available to evaluate the validity
      of these variables in other groups. OBJECTIVES: The objectives of this study were
      to 1) determine whether amount of VAT in relation to total body fatness differs
      in different race and sex groups and 2) determine which anthropometric variables
      predict amount of VAT in different race and sex groups. DESIGN: We determined the
      amount and location of body fat, including assessment of VAT by computed
      tomography, in young adult white and black men and women participating in the 10
      y follow-up of the CARDIA (Coronary Artery Risk Development in Young Adults)
      Study. RESULTS: Black men had less visceral fat (73.1+/-35.9 cm2) than white men
      (99.3+/-40 cm2), even when VAT was corrected for total body fatness. Black women
      were more obese than white women and thus had more visceral fat (75.1+/-37.5
      compared with 58.6+/-35.9 cm2, respectively). This difference disappeared when
      corrected for total body fatness. CONCLUSIONS: Both waist circumference and
      sagittal diameter were good predictors of VAT in all groups. However, the nature
      of this relation differed such that race- and sex-specific equations will likely
      be required to estimate VAT from waist circumference or sagittal diameter.

PMID- 10075321
TI  - Plasma leptin concentrations in obese children: changes during 4-mo periods with
      and without physical training.
AB  - BACKGROUND: Little is known about the effects of physical training on plasma
      leptin concentrations in children. OBJECTIVE: We sought to determine the effects
      of 4-mo periods with and without physical training on leptin in obese children
      and to explore the determinants of leptin at baseline and in response to physical
      training. DESIGN: Participants were 34 obese 7-11-y-old children randomly
      assigned to engage in physical training during either the first or second 4 mo of
      the 8-mo study. RESULTS: Total body composition, visceral adiposity, and insulin
      were all positively correlated with leptin at baseline (P < or = 0.05); however,
      only fat mass was retained in the final stepwise regression (P = 0.0001, R2 =
      0.57). Leptin decreased during the 4-mo periods of physical training and
      increased in the 4 mo after cessation of physical training (P < 0.001 for the
      time by group interaction). Decreases in leptin were greatest in children with
      higher pretraining leptin concentrations, those whose total mass increased least,
      and those whose insulin concentrations decreased most (P < or = 0.05); only
      pretraining leptin concentration (P = 0.009) and change in total mass (P =
      0.0002) were retained in the final regression (R2 = 0.53). CONCLUSIONS: In obese
      children, leptin concentration decreased during 4 mo of physical training and
      increased during a subsequent 4-mo period without physical training, fat mass was
      highly correlated with baseline leptin, and greater reductions in leptin during 4
      mo of physical training were seen in children with higher pretraining leptin and
      in those whose total mass increased least.

PMID- 10075322
TI  - Health aspects of partially defatted flaxseed, including effects on serum lipids,
      oxidative measures, and ex vivo androgen and progestin activity: a controlled
      crossover trial.
AB  - BACKGROUND: Currently there is considerable interest in the potential health
      benefits of oil seeds, such as soy and flaxseed, especially in relation to
      cardiovascular disease and cancer. OBJECTIVE: We therefore evaluated health
      aspects of partially defatted flaxseed in relation to serum lipids, indicators of
      oxidative stress, and ex vivo sex hormone activities. DESIGN: Twenty-nine
      hyperlipidemic subjects (22 men and 7 postmenopausal women) completed two 3-wk
      treatment periods in a randomized, crossover trial. Subjects were given muffins
      that contributed approximately 20 g fiber/d from either flaxseed (approximately
      50 g partially defatted flaxseed/d) or wheat bran (control) while they consumed
      self-selected National Cholesterol Education Program Step II diets. Both muffins
      had similar macronutrient profiles. Treatment phases were separated by > or = 2
      wk. RESULTS: Partially defatted flaxseed reduced total cholesterol (4.6+/-1.2%; P
      = 0.001), LDL cholesterol (7.6+/-1.8%; P < 0.001), apolipoprotein B (5.4+/-1.4%;
      P = 0.001), and apolipoprotein A-I (5.8+/-1.9%; P = 0.005), but had no effect on
      serum lipoprotein ratios at week 3 compared with the control. There were no
      significant effects on serum HDL cholesterol, serum protein carbonyl content, or
      ex vivo androgen or progestin activity after either treatment. Unexpectedly,
      serum protein thiol groups were significantly lower (10.8+/-3.6%; P = 0.007) at
      week 3 after the flaxseed treatment than after the control, suggesting increased
      oxidation. CONCLUSIONS: These data indicate that partially defatted flaxseed is
      effective in lowering LDL cholesterol. No effects on lipoprotein ratios, ex vivo
      serum androgen or progestin activity, or protein carbonyl content were observed.
      The significance of increased oxidation of protein thiol groups with flaxseed
      consumption requires further investigation.

PMID- 10075323
TI  - Effects of 2 low-fat stanol ester-containing margarines on serum cholesterol
      concentrations as part of a low-fat diet in hypercholesterolemic subjects.
AB  - BACKGROUND: Full-fat sitostanol ester-containing margarine reduces serum total
      and LDL cholesterol, but the effect of plant stanol ester-containing margarine as
      part of a low-fat, low-cholesterol diet has not been studied. OBJECTIVE: We
      investigated the cholesterol-lowering effects of 2 novel, low-fat stanol ester
      containing margarines as part of a low-fat diet recommended for
      hypercholesterolemic subjects. DESIGN: In a parallel, double-blind study, 55
      hypercholesterolemic subjects were randomly assigned after a 4-wk high-fat diet
      (baseline) to 3 low-fat margarine groups: wood stanol ester-containing margarine
      (WSEM), vegetable oil stanol ester-containing margarine (VOSEM), and control
      margarine (no stanol esters). The groups consumed the margarines for 8 wk as part
      of a diet resembling that of the National Cholesterol Education Program's Step II
      diet. The daily mean total stanol intake was 2.31 and 2.16 g in the WSEM and
      VOSEM groups, respectively. RESULTS: During the experimental period, the
      reduction in serum total cholesterol was 10.6% (P < 0.001) and 8.1% (P < 0.05)
      greater and in LDL cholesterol was 13.7% (P < 0.01) and 8.6% (P = 0.072) greater
      in the WSEM and VOSEM groups, respectively, than in the control group. Serum
      campesterol concentrations decreased 34.5% and 41.3% (P < 0.001) in the WSEM and
      VOSEM groups, respectively. Serum HDL cholesterol, sitostanol, campestanol, beta
      carotene, and fat-soluble vitamin concentrations did not change significantly
      from baseline. CONCLUSIONS: We conclude that the low-fat, plant stanol ester
      containing margarines are effective cholesterol-lowering products in
      hypercholesterolemic subjects when used as part of a low-fat, low-cholesterol
      diet. They offer an additional, clinically significant reduction in serum
      cholesterol concentrations to that obtained with a low-fat diet alone.

PMID- 10075324
TI  - A very low-fat diet is not associated with improved lipoprotein profiles in men
      with a predominance of large, low-density lipoproteins.
AB  - BACKGROUND: We found previously that men with a predominance of large LDL
      particles (phenotype A) consuming high-fat diets (40-46% fat) show less
      lipoprotein benefits of low-fat diets (20-24% fat) than do men with a high-risk
      lipoprotein profile characterized by a predominance of small LDL (phenotype B).
      Furthermore, one-third of men with phenotype A consuming a high-fat diet
      converted to phenotype B with a low-fat diet. OBJECTIVE: We investigated effects
      of further reduction in dietary fat in men with persistence of LDL subclass
      phenotype A during both high- and low-fat diets. DESIGN: Thirty-eight men who had
      shown phenotype A after 4-6 wk of both high- and low-fat diets consumed for 10 d
      a 10%-fat diet (2.7% saturates) with replacement of fat with carbohydrate and no
      change in cholesterol content or ratio of polyunsaturates to saturates. RESULTS:
      In 26 men, phenotype A persisted (stable A group) whereas 12 converted to
      phenotype B (change group). LDL cholesterol did not differ from previous values
      for 20-24%-fat diets in either group, whereas in the change group there were
      higher concentrations of triacylglycerol and apolipoprotein B; greater mass of
      HDL, large LDL-I, small LDL-III and LDL-IV, and HDL3; lower concentrations of HDL
      cholesterol, apolipoprotein A-I; and lower mass of large LDL-I and HDL2.
      CONCLUSIONS: There is no apparent lipoprotein benefit of reduction in dietary fat
      from 20-24% to 10% in men with large LDL particles: LDL-cholesterol concentration
      was not reduced, and in a subset of subjects there was a shift to small LDL along
      with increased triacylglycerol and reduced HDL-cholesterol concentrations.

PMID- 10075325
TI  - Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations
      as compared with soy protein.
AB  - BACKGROUND: Substitution of soy protein for casein in the diet decreases LDL
      cholesterol and increases HDL cholesterol. How the 2 proteins affect
      lipoprotein(a) [Lp(a)], an independent risk factor for coronary artery disease,
      is unknown. OBJECTIVE: We compared the effects of dietary soy protein and casein
      on plasma Lp(a) concentrations. DESIGN: Nine normolipidemic men were studied
      initially while consuming their habitual, self-selected diets, and then, in a
      crossover design, while consuming 2 liquid-formula diets containing either casein
      or soy protein. The dietary periods lasted 45 d (n = 7) or 33 d (n = 2). Fasting
      total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol, and Lp(a)
      concentrations were measured throughout. RESULTS: After 30 d of each diet, the
      mean concentration of Lp(a) was not significantly different after the soy-protein
      and self-selected diets. However, Lp(a) decreased by an average of 50% (P <
      0.001) after the casein diet as compared with concentrations after both the soy
      protein and self-selected diets. Two weeks after subjects switched from the self
      selected to the soy-protein diet, Lp(a) increased by 20% (P = 0.065), but
      subsequently decreased to baseline. In contrast, the switch to the casein diet
      did not cause an increase in Lp(a), but instead a continuing decrease in mean
      concentrations to 65% below baseline (P < 0.0002). Total cholesterol, LDL
      cholesterol, and HDL cholesterol were significantly lower > or =30 d after both
      the casein and soy-protein diets than after the self-selected diet (P < 0.001).
      HDL cholesterol was 11% higher after the soy-protein diet than after the casein
      diet (P < 0.002), but LDL cholesterol, total cholesterol, and triacylglycerol
      were not significantly different after the casein and soy-protein diets.
      CONCLUSION: These findings indicate that soy protein may have an Lp(a)-raising
      effect, potentially detrimental to its use in antiatherogenic diets.

PMID- 10075326
TI  - Bioelectrical impedance plethysmographic analysis of body composition in
      critically injured and healthy subjects.
AB  - BACKGROUND: Determination of body composition during critical illness is complex
      because of various patient-related and technical factors. Bioelectrical impedance
      is a promising technique for the analysis of body composition; however, its
      clinical utility in critically injured patients is unknown. OBJECTIVE: The
      purpose of this study was to compare bioelectrical impedance with metabolic
      activity in healthy and critically injured patients. If bioelectrical impedance
      accurately determines body composition during critical illness, the slope between
      body-composition variables and oxygen consumption would be the same in critically
      injured and healthy subjects. DESIGN: There is a strong linear relation between
      body composition and metabolic activity. In the present study, body composition
      (fat-free mass and body cell mass) was determined by using bioelectrical
      impedance and resting metabolic activity (metabolic rate and oxygen consumption)
      by using gas exchange analysis in a group of healthy and critically injured
      subjects. The relation between these variables was compared by using linear
      regression to a similar relation established by hydrostatic weighing in a large
      historical control group. RESULTS: The slope of the line relating fat-free mass
      to resting metabolic rate was the same in the healthy and critically ill groups
      (P = 0.62) and each was similar to the slope of the line for the control group.
      However, in 37% of the critically injured group, overhydration contributed to an
      increase in fat-free mass, disturbing the relation with resting metabolic rate.
      The slope of the line relating body cell mass to oxygen consumption in our
      healthy and critically ill groups was almost identical. CONCLUSION: These results
      support the use of bioelectrical impedance to determine body cell mass in healthy
      and critically ill subjects.

PMID- 10075327
TI  - Relative influences of sex, race, environment, and HIV infection on body
      composition in adults.
AB  - BACKGROUND: The factors that control body composition in disease are uncertain.
      OBJECTIVE: We planned to compare the relative influences of HIV infection, sex,
      race, and environment on body composition. METHODS: We analyzed results of body
      composition studies performed by bioelectrical impedance analysis in 1415 adults
      from 2 cohorts: white and African American men and women from the United States,
      and African men and women (279 HIV-infected and 1136 control). The effects of sex
      and HIV infection on weight, body cell mass, and fat-free mass were analyzed by
      using both unadjusted and age-, weight-, and height-adjusted data. RESULTS:
      Control men weighed more and had more body cell mass and fat-free mass than did
      control women, although control women had more fat. The strongest correlates with
      body composition were height and weight, followed by sex. HIV infection, age,
      environment, and race. Control men and women weighed more and had more body cell
      mass, fat-free mass, and fat than did HIV-infected men. However, differences in
      body composition between HIV-infected and control groups were strongly influenced
      by sex. Of the differences in weight between HIV-infected and uninfected
      subjects, fat-free mass accounted for 51% in men but only 18% in women, in whom
      the remainder was fat. Sex effects were similar in African and American groups.
      CONCLUSIONS: Sex has a marked effect on the changes in body composition during
      HIV infection, with women losing disproportionately more fat than men. Sex
      related differences in body composition were narrower in the HIV-infected groups.
      Race and environment had smaller effects than sex and HIV infection.

PMID- 10075328
TI  - Dietary variety within food groups: association with energy intake and body
      fatness in men and women.
AB  - BACKGROUND: Short-term experimental studies suggest that dietary variety may
      influence body fatness but no long-term human studies have been reported.
      OBJECTIVE: The purpose of this study was to determine whether dietary variety
      within food groups influences energy intake and body fatness. DESIGN: Seventy-one
      healthy men and women (aged 20-80 y), who provided accurate reports of dietary
      intake and completed a body-composition assessment, were studied. RESULTS:
      Dietary variety was positively associated with energy intake within each of 10
      food groups (r = 0.27-0.56, P < 0.05). In multiple regression analysis with age
      and sex controlled for, dietary variety of sweets, snacks, condiments, entrees,
      and carbohydrates (as a group) was positively associated with body fatness
      (partial r = 0.38, P = 0.001) whereas variety from vegetables was negatively
      associated (partial r = -0.31, P = 0.01) (R2 = 0.46, P < 0.0001). In separate
      models, both a variety ratio (variety of vegetables/variety of sweets, snacks,
      condiments, entrees, and carbohydrates) and percentage dietary fat were
      significant predictors of body fatness (controlled for age and sex, partial r = 
      0.39 and 0.31, respectively, P < 0.01). However, dietary fat was no longer
      significantly associated with body fatness when the variety ratio and dietary fat
      were included in the same model. CONCLUSIONS: Our data, coupled with those of
      previous short-term studies, suggest that a high variety of sweets, snacks,
      condiments, entrees, and carbohydrates coupled with a low variety of vegetables
      promotes long-term increases in energy intake and body fatness. These findings
      may help explain the rising prevalence of obesity.

PMID- 10075329
TI  - Rapidly available glucose in foods: an in vitro measurement that reflects the
      glycemic response.
AB  - BACKGROUND: A chemically based classification of dietary carbohydrates that takes
      into account the likely site, rate, and extent of digestion is presented. The
      classification divides dietary carbohydrates into sugars, starch fractions, and
      nonstarch polysaccharides, and groups them into rapidly available glucose (RAG)
      and slowly available glucose (SAG) as to the amounts of glucose (from sugar and
      starch, including maltodextrins) likely to be available for rapid and slow
      absorption, respectively, in the human small intestine. OBJECTIVE: We hypothesize
      that RAG is an important food-related determinant of the glycemic response.
      DESIGN: The measurement of RAG, SAG, and starch fractions by an in vitro
      technique is described, based on the measurement by HPLC of the glucose released
      from a test food during timed incubation with digestive enzymes under
      standardized conditions. Eight healthy adult subjects consumed 8 separate test
      meals ranging in RAG content from 11 to 49 g. RESULTS: The correlation between
      glycemic response and RAG was highly significant (P < 0.0001) and a given
      percentage increase in RAG was associated with the same percentage increase in
      glycemic response. After subject variation was accounted for, RAG explained 70%
      of the remaining variance in glycemic response. CONCLUSIONS: We show the
      significance of in vitro measurements of RAG in relation to glycemic response in
      human studies. The simple in vitro measurement of RAG and SAG is of physiologic
      relevance and could serve as a tool for investigating the importance of the
      amount, type, and form of dietary carbohydrates for health.

PMID- 10075330
TI  - Variation by body mass index and age in waist-to-hip ratio associations with
      glycemic status in an aboriginal population at risk for type 2 diabetes in
      British Columbia, Canada.
AB  - BACKGROUND: It is unclear whether obesity and age modify or confound relations
      between abdominal adiposity and metabolic risk factors for type 2 diabetes.
      OBJECTIVE: Our objective was assess the consistency of relations between
      abdominal adiposity and glycemic variables across discrete categories of obesity
      and age. DESIGN: We performed a stratified analysis of prevalence data from a
      rural screening initiative in British Columbia, Canada. Subjects were Salishan
      Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age:
      18-80 y; body mass index (BMI, in kg/m2): 17.0-48.2]. We measured waist-to-hip
      ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb A1c), and 2-h
      glucose concentrations (2 categories); and BMI (4 categories). BMI and age
      specific odds ratios (ORs) and 95% CIs were calculated. RESULTS: WHR-glycemic
      variable relations were not consistent across BMI and age strata. Risks
      associated with high WHR were: for persons with BMIs from 25 to 29, elevated
      insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb A1c (OR: 16.23; 95% CI: 2.04,
      101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations
      [OR: indeterminate (+infinity); 95% CI: 1.89, +infinity]; and, for persons aged
      35-49 y, elevated Hb A1c (OR: +infinity; 95% CI: 3.17, +infinity) and 2-h glucose
      (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. CONCLUSIONS: WHR discriminates
      risk of type 2 diabetes in overweight but not obese individuals. Abdominal
      adiposity is associated with elevated insulin concentrations in younger age
      groups and with impaired glucose control in middle-aged groups, suggesting
      metabolic staging by age on a continuum from insulin resistance to impaired
      glucose tolerance.

PMID- 10075331
TI  - Comparison of indirect calorimetry, the Fick method, and prediction equations in
      estimating the energy requirements of critically ill patients.
AB  - BACKGROUND: Accurate measurement of resting energy expenditure (REE) is helpful
      in determining the energy needs of critically ill patients requiring nutritional
      support. Currently, the most accurate clinical tool used to measure REE is
      indirect calorimetry, which is expensive, requires trained personnel, and has
      significant error at higher inspired oxygen concentrations. OBJECTIVE: The
      purpose of this study was to compare REE measured by indirect calorimetry with
      REE calculated by using the Fick method and prediction equations by Harris
      Benedict, Ireton-Jones, Fusco, and Frankenfield. DESIGN: REEs of 36 patients [12
      men and 24 women, mean age 58+/-22 y and mean Acute Physiology and Chronic Health
      Evaluation II score 22+/-8] in a hospital intensive care unit and receiving
      mechanical ventilation and total parenteral nutrition (TPN) were measured for >
      or = 15 min by using indirect calorimetry and compared with REEs calculated from
      a mean of 2 sets of hemodynamic measurements taken during the metabolic testing
      period with an oximetric pulmonary artery catheter. RESULTS: Mean REE by indirect
      calorimetry was 8381+/-1940 kJ/d and correlated poorly with the other methods
      tested (r = 0.057-0.154). This correlation did not improve after adjusting for
      changes in respiratory quotient (r2 = 0.28). CONCLUSIONS: These data do not
      support previous findings showing a strong correlation between REE determined by
      the Fick method and other prediction equations and indirect calorimetry. In
      critically ill patients receiving TPN, indirect calorimetry, if available,
      remains the most appropriate clinical tool for accurate measurement of REE.

PMID- 10075332
TI  - Association of dietary protein intake and coffee consumption with serum
      homocysteine concentrations in an older population.
AB  - BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been
      implicated in the pathogenesis of atherosclerotic cardiovascular disease.
      Previous studies identified suboptimal nutritional status and dietary intake of
      folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy.
      OBJECTIVE: We identified other nutritional factors associated with tHcy in 260
      retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed
      observational analyses of baseline and 2-4-mo follow-up data collected in a study
      designed to test the feasibility of conducting a large-scale clinical trial of
      vitamin supplements by mail. The study population consisted of 151 women and 109
      men with a median age of 64 y. At baseline, each participant completed a food
      frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS:
      In multivariable linear regression and generalized linear models, there was an
      independent, inverse dose-response relation between dietary protein and In tHcy
      (P = 0.002) and a positive, significant dose-response relation between coffee
      consumption and In tHcy (P for trend = 0.01). Other significant predictors of In
      tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B
      vitamins (inverse; P = 0.03). In stratified analyses restricted to persons
      receiving standard multivitamin therapy, the association of 1n tHcy with dietary
      protein and coffee persisted. CONCLUSIONS: These results support the hypothesis
      that increased protein intake and decreased coffee consumption may reduce tHcy
      and potentially prevent atherosclerotic cardiovascular disease and other disease
      outcomes.

PMID- 10075333
TI  - Serum and red blood cell folate concentrations, race, and education: findings
      from the third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Little is known about the relations between race or ethnicity,
      educational attainment, and serum and red blood cell folate concentrations.
      OBJECTIVE: We examined the relation between educational attainment and serum and
      red blood cell folate concentrations in 8457 white, African American, and Mexican
      American men and women aged > or = 17 y. DESIGN: We performed a cross-sectional
      analysis using data from Phase 1 of the third National health and Nutrition
      Examination Survey (1988-1991). RESULTS: White men had significantly higher
      adjusted serum and red blood cell folate concentrations (16.9 and 502.6 nmol/L,
      respectively) than did African American men (15.6 and 423.3 nmol/L, respectively)
      or Mexican American men (16.0 and 457.0 nmol/L, respectively); white women had
      significantly higher concentrations (18.4 and 515.9 nmol/L, respectively) than
      did African American women (16.3 and 415.4 nmol/L, respectively) or Mexican
      American women (15.9 and 455.7 nmol/L, respectively). For the entire sample, rank
      correlation coefficients between educational attainment and serum and red blood
      cell folate were 0.11 and 0.12, respectively, and were larger in white
      participants than in other participants. No significant linear trends between
      adjusted serum or red blood cell folate and educational attainment were found.
      Among participants with > 12 y of education, the mean adjusted concentrations of
      serum folate were 15% and 18% lower and those of red blood cell were 18% and 22%
      lower in African American men and women than in white men and women,
      respectively. CONCLUSIONS: African Americans and Mexican Americans could benefit
      most from public health programs to boost folate intakes by encouraging increased
      intake of folate-rich foods and vitamin supplements.

PMID- 10075334
TI  - Serum total homocysteine concentrations in adolescent and adult Americans:
      results from the third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: The elevation of circulating total homocysteine concentrations in a
      fasting state is associated with an increased risk of occlusive vascular disease.
      OBJECTIVE: The primary goals of this study were to describe the distribution of
      serum total homocysteine concentrations in the United States and to test for
      differences in homocysteine concentrations among sex, age, and race-ethnicity
      categories. DESIGN: Using surplus sera from phase 2 of the third National Health
      and Nutrition Examination Survey, we measured serum total homocysteine
      concentrations for a nationally representative sample of 3766 males and 4819
      females aged > or = 12 y. RESULTS: Age-adjusted geometric mean total homocysteine
      concentrations were 9.6 and 7.9 mmol/L in non-Hispanic white males and females,
      9.8 and 8.2 mmol/L in non-Hispanic black males and females, and 9.4 and 7.4
      mmol/L in Mexican American males and females, respectively. Age-adjusted
      geometric mean total homocysteine concentrations were significantly lower in
      females than in males in each race-ethnicity group (P < 0.01) and were
      significantly lower in Mexican American females than in non-Hispanic white and
      non-Hispanic black females (P < 0.01). There was a significant age-sex
      interaction (P < 0.01), reflecting the fact that homocysteine concentrations in
      females tended to diverge from those in males at younger ages and converge with
      those in males at older ages. CONCLUSIONS: The first data on homocysteine
      concentrations in a nationally representative sample of Americans confirm the age
      and sex differences reported previously in nonrepresentative samples. These data
      also indicate that differences between Mexican American and non-Hispanic females
      may influence circulating homocysteine concentrations.

PMID- 10075335
TI  - Effect of reducing the phytate content and of partially hydrolyzing the protein
      in soy formula on zinc and copper absorption and status in infant rhesus monkeys
      and rat pups.
AB  - BACKGROUND: Although soy formulas have been designed to meet the nutrient
      requirements of human infants, they also contain phytate, which may negatively
      affect trace element absorption. OBJECTIVE: We evaluated the effect of removing
      phytate on zinc and copper absorption and status in infant rhesus monkeys and
      suckling rat pups and evaluated differences between intact and partially
      hydrolyzed soy protein. DESIGN: In monkeys, regular and low-phytate soy formulas
      were fed exclusively for 4 mo and whole-body absorption and retention of 65Zn,
      67Cu, 59Fe, 54Mn, and 47Ca were determined at different time points with a whole
      body counter. Subsequently, zinc and copper absorption from several human infant
      formulas and the effect of phytate concentration were evaluated in suckling rat
      pups by using 65Zn and 64Cu. Finally, infant rhesus monkeys were fed low-phytate
      formulas with intact or hydrolyzed soy protein for 4 mo and plasma zinc and
      copper were measured monthly. RESULTS: In the first monkey study, zinc absorption
      at 1 mo was higher from low-phytate soy formula (36%) than from regular soy
      formula (22%), whereas there was no significant difference between groups in the
      absorption of other minerals. Plasma copper was significantly lower in monkeys
      fed low-phytate soy formula from 2 to 4 mo. In rat pups, zinc absorption was
      significantly higher from low-phytate soy formula (78%) than from regular soy
      formula (51%) and hydrolysis of the protein had no significant effect. Phytate
      content or protein hydrolysis did not significantly affect copper absorption. In
      the second monkey study, plasma copper concentrations were highest in monkeys fed
      the low-phytate, hydrolyzed-protein soy formula. CONCLUSION: Reducing the phytate
      content and partially hydrolyzing the protein in soy formula had a beneficial
      effect on zinc and copper absorption and status in infant rhesus monkeys.

PMID- 10075336
TI  - Effect of iron-, iodine-, and beta-carotene-fortified biscuits on the
      micronutrient status of primary school children: a randomized controlled trial.
AB  - BACKGROUND: Deficiencies of iron, iodine, and vitamin A are prevalent worldwide
      and can affect the mental development and learning ability of schoolchildren.
      OBJECTIVE: The aim of this study was to determine the effect of micronutrient
      fortified biscuits on the micronutrient status of primary school children.
      DESIGN: Micronutrient status was assessed in 115 children aged 6-11 y before and
      after consumption of biscuits (fortified with iron, iodine, and beta-carotene)
      for 43 wk over a 12-mo period and was compared with that in a control group (n =
      113) who consumed nonfortified biscuits. Cognitive function, growth, and
      morbidity were assessed as secondary outcomes. RESULTS: There was a significant
      between-group treatment effect on serum retinol, serum ferritin, serum iron,
      transferrin saturation, and urinary iodine (P <0.0001) and in hemoglobin and
      hematocrit (P <0.05). The prevalence of low serum retinol concentrations (<0.70
      micromol/L) decreased from 39.1% to 12.2%, of low serum ferritin concentrations
      (<20 microg/L) from 27.8% to 13.9%, of anemia (hemoglobin <120 g/L) from 29.6% to
      15.6%, and of low urinary iodine concentrations (<100 microg/L) from 97.5% to
      5.4%. There was a significant between-group treatment effect (P <0.05) in
      cognitive function with the digit span forward task (short-term memory). Fewer
      school days were missed in the intervention than in the control group because of
      respiratory- (P = 0.097) and diarrhea-related (P = 0.013) illnesses. The
      intervention had no effect on anthropometric status [corrected]. CONCLUSIONS:
      Fortified biscuits resulted in a significant improvement in the micronutrient
      status of primary school children from a poor rural community and also appeared
      to have a favorable effect on morbidity and cognitive function [corrected].

PMID- 10075337
TI  - Bioavailability of biotin given orally to humans in pharmacologic doses.
AB  - BACKGROUND: Patients with carboxylase deficiency are treated with pharmacologic
      doses of biotin. OBJECTIVE: We sought to determine the bioavailability of biotin
      at pharmacologic doses. DESIGN: Biotin was administered orally (2.1, 8.2, or 81.9
      micromol) or intravenously (18.4 micromol) to 6 healthy adults in a crossover
      design with > or =2 wk between each biotin administration. Before and after each
      administration, timed 24-h urine samples were collected. Urinary biotin and
      biotin metabolites were analyzed by an HPLC avidin-binding assay. RESULTS:
      Urinary recoveries of biotin plus metabolites were similar (approximately 50%)
      after the 2 largest oral doses and the 1 intravenous dose, suggesting 100%
      bioavailability of the 2 largest oral doses. For unexplained reasons, the
      apparent recovery of the smallest oral dose was about twice that of the other
      doses. For all 4 doses, biotin accounted for >50% of the total of biotin and
      biotin metabolites in urine. Bisnorbiotin (13-23%), biotin-d,l-sulfoxide (5-13%),
      bisnorbiotin methyl ketone (3-9%), and biotin sulfone (1-3%) accounted for the
      remainder. The percentage excretion of biotin was greater when biotin was
      administered intravenously and for the largest oral dose than for the 2 smallest
      oral doses. CONCLUSION: Our data provide evidence that oral biotin is completely
      absorbed even when pharmacologic doses are administered. Biotin metabolites
      account for a substantial portion of total urinary excretion and must be
      considered in bioavailability studies. We speculate that renal losses of biotin
      (as a percentage of the dose administered) are moderately elevated when
      pharmacologic doses of biotin are administered.

PMID- 10075338
TI  - Influence of prenatal iron and zinc supplements on supplemental iron absorption,
      red blood cell iron incorporation, and iron status in pregnant Peruvian women.
AB  - BACKGROUND: It is estimated that 60% of pregnant women worldwide are anemic.
      OBJECTIVE: We aimed to examine the influence of iron status on iron absorption
      during pregnancy by measuring supplemental iron absorption, red blood cell iron
      incorporation, and iron status in pregnant women. DESIGN: Subjects were 45
      pregnant Peruvian women (33+/-1 wk gestation), of whom 28 received daily prenatal
      supplements containing 60 mg Fe and 250 microg folate without (Fe group, n = 14)
      or with (Fe+Zn group, n = 14) 15 mg Zn, which were were consumed from week 10 to
      24 of gestation until delivery. The remaining 17 women (control) received no
      prenatal supplementation. Iron status indicators and isotopes were measured in
      maternal blood collected 2 wk postdosing with oral (57Fe) and intravenous (58Fe)
      stable iron isotopes. RESULTS: Maternal serum ferritin and folate concentrations
      were significantly influenced by supplementation (P < 0.05). Serum iron was also
      significantly higher in the Fe than in the Fe+Zn (P < 0.03) or control (P <
      0.001) groups. However, the supplemented groups had significantly lower serum
      zinc concentrations than the control group (8.4+/-2.3 and 10.9+/-1.8 micromol/L,
      respectively, P < 0.01). Although percentage iron absorption was inversely
      related to maternal serum ferritin concentrations (P = 0.036), this effect was
      limited and percentage iron absorption did not differ significantly between
      groups. CONCLUSIONS: Because absorption of nonheme iron was not substantially
      greater in pregnant women with depleted iron reserves, prenatal iron
      supplementation is important for meeting iron requirements during pregnancy.

PMID- 10075339
TI  - Influence of dietary fat on the nutrient intake and growth of children from 1 to
      5 y of age: the Special Turku Coronary Risk Factor Intervention Project.
AB  - BACKGROUND: Excessive decreases in fat intake in young children have been linked
      with low intakes of energy and nutrients and possible growth failure. OBJECTIVE:
      We evaluated nutrient intakes and growth of healthy children with different fat
      intakes during the first 5 y of life. DESIGN: In the Special Turku Coronary Risk
      Factor Intervention Project (STRIP), 7-mo-old children were randomly assigned to
      an intervention aimed at reduced consumption of saturated fat and cholesterol (n
      = 540) or to a control group (n = 522). This analysis comprises data for children
      for whom > or = 6 of 8 possible 3-4-d food records were available (n = 730; 353
      females). Children were divided according to fat intake pattern (percentage of
      energy) between the ages of 13 mo and 5 y into groups with continuously high fat
      intake (5% of children), increasing fat intake (5%), continuously low fat intake
      (5%), decreasing fat intake (5%), and average fat intake (80%). Children's energy
      and nutrient intakes and growth were then compared by analysis of variance.
      RESULTS: Fat intake at 13 mo of age was particularly low (21% of energy) in the
      increasing fat intake group and in the continuously low fat intake group (22% of
      energy at 13 mo; 26% of energy at 5 y). Growth of children in all 5 fat intake
      groups, however, was not significantly different throughout the study period.
      Intakes of vitamins and minerals, except of vitamin D, met recommended dietary
      allowances in all fat intake groups. CONCLUSION: Nutrient intakes and growth were
      not significantly different in children whose fat intake patterns differed
      between 13 mo and 5 y of age.

PMID- 10075340
TI  - Energy intake, not energy output, is a determinant of body size in infants.
AB  - BACKGROUND: It has been proposed that the primary determinants of body weight at
      1 y of age are genetic background, as represented by parental obesity, and low
      total energy expenditure. OBJECTIVE: The objective was to determine the relative
      contributions of genetic background and energy intake and expenditure as
      determinants of body weight at 1 y of age. DESIGN: Forty infants of obese and 38
      infants of lean mothers, half boys and half girls, were assessed at 3 mo of age
      for 10 risk factors for obesity: sex, risk group (obese or nonobese mothers),
      maternal and paternal body mass index, body weight, feeding mode (breast, bottle,
      or both), 3-d energy intake, nutritive sucking behavior during a test meal, total
      energy expenditure, sleeping energy expenditure, and interactions among them.
      RESULTS: The only difference between risk groups at baseline was that the high
      risk group sucked more vigorously during the test meal. Four measures accounted
      for 62% of the variability in weight at 12 mo: 3-mo weight (41%, P = 0.0001),
      nutritive sucking behavior (9%, P = 0.0002), 3-d food intake (8%, P = 0.0002),
      and male sex (3%, P = 0.05). Food intake and sucking behavior at 3 mo accounted
      for similar amounts of variability in weight-for-length, body fat, fat-free mass,
      and skinfold thickness at 12 mo. Contrary to expectations, neither total nor
      sleeping energy expenditure at 3 mo nor maternal obesity contributed to measures
      of body size at 12 mo. CONCLUSIONS: Energy intake contributes significantly to
      measures of body weight and composition at 1 y of age; parental obesity and
      energy expenditure do not.

PMID- 10075341
TI  - Comparison of growth status of patients with cystic fibrosis between the United
      States and Canada.
AB  - BACKGROUND: Differences in growth status of patients with cystic fibrosis (CF)
      between the United States and Canada were reported in the 1980s based on analysis
      of data from 2 regional CF centers. OBJECTIVE: We evaluated the current growth
      status of the entire CF population in the United States and Canada in view of
      recent advances in the treatment of CF. DESIGN: Growth data from the 1992-1994 CF
      Patient Registries were analyzed. RESULTS: Mean height and weight were at
      approximately the 30th percentile for children with CF in the United States. Mean
      height and weight were 4-5 percentiles higher in children with CF in Canada than
      in those in the United States (P < 0.01), but percentages of ideal weight (104%)
      were similar in both populations. In adults with CF, mean height was similar at
      the 37th percentile; however, weight (26th compared with the 21st percentiles)
      and percentage of ideal weight (93% compared with 90%) were significantly higher
      in Canada than in the United States. Differences related to sex and age were
      similar in both countries for all indexes, which showed a high prevalence of
      underweight in infants and in older patients, but little sex discrepancy.
      CONCLUSION: We observed substantially smaller differences in the growth indexes
      of CF patients between the United States and Canada compared with results from
      the 1980s. These findings reflect significant improvements in the nutritional
      status of US patients in recent years. However, caution is required in the direct
      comparison of mean percentiles from reports using different growth standards
      because there are systematic differences in growth standards, which affect, in
      particular, the comparison of growth in males and females.

PMID- 10075342
TI  - Leucine metabolism in preterm infants receiving parenteral nutrition with medium
      chain compared with long-chain triacylglycerol emulsions.
AB  - BACKGROUND: Although medium-chain triacylglycerols (MCTs) may be utilized more
      efficiently than long-chain triacylglycerols (LCTs), their effect on protein
      metabolism remains controversial. OBJECTIVE: The aim of the study was to compare
      the effects of mixed MCT-LCT and pure LCT emulsions on leucine metabolism in
      preterm infants. DESIGN: Fourteen preterm [gestational age: 30+/-1 wk; birth
      weight: 1409+/-78 g (x +/- SE)] neonates were randomly assigned to receive, from
      the first day of life, either a 50:50 MCT-LCT (mixed MCT group; n = 7) or an LCT
      (LCT group; n = 7) lipid emulsion as part of an isonitrogenous, isoenergetic
      total parenteral nutrition program. On the fourth day, infants received
      intravenous feeding providing 3 g lipid, 15 g glucose, and 3 g amino acids kg(-1)
      x d(-1) and underwent 1) indirect calorimetry and 2) a primed, 2-h infusion of
      H13CO3Na to assess the recovery of 13C in breath, immediately followed by 3) a 3
      h infusion of L-[1-13C]leucine. RESULTS: The respiratory quotient tended to be
      slightly but not significantly higher in the mixed MCT than in the LCT group
      (0.96+/-0.06 compared with 0.93+/-0.03). We did not detect a significant
      difference between the mixed MCT and LCT groups with regard to release of leucine
      from protein breakdown (B; 309+/-40 compared with 257+/-46 micromol x kg(-1) x h(
      1)) and nonoxidative leucine disposal (NOLD; 296+/-36 compared with 285+/-49
      micromol x kg(-1) x h(-1)). In contrast, leucine oxidation was greater in the
      mixed MCT than in the LCT group (113+/-10 compared with 67+/-10 micromol x kg(-1)
      x h(-1); P = 0.007). Net leucine balance (NOLD - B) was less positive in the
      mixed MCT than in the LCT group (-14+/-9 compared with 28+/-10 micromol x kg(-1)
      x h(-1); P = 0.011). CONCLUSION: Mixed MCTs may not be as effective as LCT
      containing emulsions in promoting protein accretion in parenterally fed preterm
      neonates.

PMID- 10075343
TI  - Oligofructose stimulates calcium absorption in adolescents.
AB  - BACKGROUND: In rats, nondigestible oligosaccharides stimulate calcium absorption.
      Recently, this effect was also found in human subjects. OBJECTIVE: The objective
      of the study was to investigate whether consumption of 15 g oligofructose/d
      stimulates calcium absorption in male adolescents. DESIGN: Twelve healthy, male
      adolescents aged 14-16 y received, for 9 d, 15 g oligofructose or sucrose
      (control treatment) daily over 3 main meals. The treatments were given according
      to a randomized, double-blind, crossover design, separated by a 19-d washout
      period. On the 8th day of each treatment period, 44Ca was given orally with a
      standard breakfast containing approximately 200 mg Ca. Within half an hour after
      administration of 44Ca, 48Ca was administered intravenously. Fractional calcium
      absorption was computed from the enrichment of 44Ca:43Ca and 48Ca:43Ca in 36-h
      urine samples, which was measured by inductively coupled plasma mass
      spectrometry. RESULTS: An increase in true fractional calcium absorption (%) was
      found after consumption of oligofructose (mean difference +/- SE of difference:
      10.8+/-5.6; P < 0.05, one sided). The results are discussed in relation to the
      methods used. CONCLUSION: Fifteen grams of oligofructose per day stimulates
      fractional calcium absorption in male adolescents.

PMID- 10075344
TI  - Human metabolism of mammalian lignan precursors in raw and processed flaxseed.
AB  - BACKGROUND: The mammalian lignans enterolactone and enterodiol are produced in
      the colon by the action of bacteria on the plant precursor secoisolariciresinol
      diglycoside, which is found in high concentrations in flaxseed. OBJECTIVE: Two
      experiments were conducted to determine 1) whether there is a dose response in
      urinary lignan excretion with increasing flaxseed intake, 2) whether flaxseed
      processing affects lignan excretion, 3) peak plasma lignan concentrations, and 4)
      plasma lignan concentrations after chronic supplementation. DESIGN: Nine healthy
      young women supplemented their diets with 5, 15, or 25 g raw or 25 g processed
      (muffin or bread) flaxseed for 7 d during the follicular phase of their menstrual
      cycles. Twenty-four-hour urine samples were collected at baseline and on the
      final day of supplementation. As an adjunct to the 25-g-flaxseed arm, subjects
      consumed the supplement for an additional day and blood and urine samples were
      collected at specific intervals. All blood and urine samples were analyzed for
      enterolactone and enterodiol by gas chromatography-mass spectroscopy. RESULTS: A
      dose-dependent urinary lignan response to raw flaxseed was observed (r = 0.72, P
      < 0.001). The processing of flaxseed as a muffin or bread did not affect the
      quantity of lignan excretion. Plasma lignan concentrations were greater (P < or =
      0.05) than baseline by 9 h after flaxseed ingestion (29.35+/-3.69 and 51.75+/
      7.49 nmol/L, respectively). The total plasma area under the curve was higher on
      the eighth than on the first day (1840.15+/-343.02 and 1027.15+/-95.71 nmol x
      h/L, respectively). CONCLUSION: Mammalian lignan production from flaxseed
      precursors is dependent on time and dose but not on processing.

PMID- 10075345
TI  - Composition of enteral diets and meals providing optimal absorption rates of
      nutrients in mini pigs.
AB  - BACKGROUND: Commercial enteral diets differ widely in nutrient composition. It is
      unknown whether the nutrient composition of the diets influences intestinal
      absorption. OBJECTIVE: The objective of this study was to investigate the effects
      of different enteral diets providing 60% of energy as carbohydrate, protein, or
      fat or 33.3% of energy from each nutrient on intestinal absorption in mini pigs.
      DESIGN: Kinetics of nutrient absorption were determined by perfusing a 150-cm
      jejunal segment. The kinetics of absorption were used to determine optimal
      relations between the absorption and recovery of each nutrient. From these data,
      the optimal nutrient composition of the diets providing complete absorption of
      the macronutrients in the shortest intestinal length was evaluated. Absorption of
      nutrients was further determined after oral administration of 4 corresponding
      meals. RESULTS: With all enteral diets, the absorption of nutrients displayed
      saturation kinetics. Absorption rates of carbohydrate were significantly larger
      than those of fat and protein. Consequently, the amounts of nutrients remaining
      unabsorbed per unit length of jejunum differed among the macronutrients. After
      administration of various test meals, the length of the small intestine required
      for complete absorption of the nutrients depended on the composition of the
      meals. The shortest intestinal length for complete absorption was needed for a
      diet providing 48% of energy as carbohydrate, 23% as protein, and 29% as fat.
      This composition closely matched the nutritional requirements. CONCLUSION: The
      nutrient composition of diets can optimize intestinal absorption. This may be
      especially important in patients with malabsorption or short-bowel syndrome.

PMID- 10075346
TI  - Age-related hearing loss, vitamin B-12, and folate in elderly women.
AB  - BACKGROUND: Hearing impairment is 1 of the 4 most prevalent chronic conditions in
      the elderly. However, the biological basis of age-related hearing loss is
      unknown. OBJECTIVE: The objective was to test the hypothesis that age-related
      hearing loss may be associated with poor vitamin B-12 and folate status. DESIGN:
      A thorough audiometric assessment was conducted in 55 healthy women aged 60-71 y.
      Hearing function was determined by the average of pure-tone air conduction
      thresholds at 0.5, 1, 2, and 4 kHz and was categorized into 2 groups for logistic
      regression analyses: normal hearing (<20 dB hearing level; n = 44) and impaired
      hearing (> or = 20 dB hearing level; n = 11). RESULTS: Mean age was the same (65
      y) for the normal hearing and impaired hearing groups. Pure-tone averages were
      inversely correlated with serum vitamin B-12 (r = -0.58, P = 0.0001) and red cell
      folate (r = -0.37, P = 0.01). Women with impaired hearing had 38% lower serum
      vitamin B-12 (236 compared with 380 pmol/L, respectively, P = 0.008) and 31%
      lower red cell folate (425 compared with 619 nmol/L, respectively, P = 0.02) than
      women with normal hearing. Among participants who did not take supplements
      containing vitamin B-12 or folate, women with impaired hearing had 48% lower
      serum vitamin B-12 (156 compared with 302 pmol/L, respectively, P = 0.0007) and
      43% lower red cell folate (288 compared with 502 nmol/L, respectively, P = 0.001)
      than women with normal hearing. CONCLUSION: Poor vitamin B-12 and folate status
      may be associated with age-related auditory dysfunction.

PMID- 10075347
TI  - Smoking and oxidative stress.

PMID- 10075348
TI  - The potato's placement in the dietary pyramid.

PMID- 10075349
TI  - Villous atrophy and nutritional status in celiac disease.

PMID- 10075350
TI  - High-sucrose diets and insulin sensitivity.

PMID- 10075351
TI  - Correcting for vitamin A turnover in isotope-dilution studies.

PMID- 10075352
TI  - The dorsal liver: an analysis.

PMID- 10075353
TI  - Surgical treatment for ampullary carcinoma.

PMID- 10075354
TI  - The effect of vaginal delivery on anal function.
AB  - The commonest cause of faecal incontinence is considered to be childbirth. In
      this review we consider the available data on the prevalence of faecal
      incontinence in the community and the incidence of incontinence after childbirth.
      The results and implications of studies on childbirth using anal manometry,
      neurophysiological tests and anal ultrasound are discussed. The development of
      symptoms are more likely with a third degree tear and forceps delivery. Reduced
      resting and squeeze pressures are seen early after vaginal delivery with recovery
      noted with time. Reduced pressures have been seen in symptomatic and asymptomatic
      women and there is no correlation of the pressures with the presence or absence
      of a sphincter defect or evidence of pudendal neuropathy. Anal manometry can not
      be used as an indication of muscle or nerve injury. Both sphincter defects and
      evidence of pudendal neuropathy are common after vaginal delivery but these are
      not necessarily associated with symptoms. It is suggested that such occult
      sphincter injuries may go on to be symptomatic in later life. The number of these
      injuries, however, is far greater than the documented prevalence of incontinence
      in the community, and hence many must remain asymptomatic. Their true clinical
      significance remains uncertain.

PMID- 10075355
TI  - Australia's breast surgery workload is changing: comparison of a metropolitan and
      a rural hospital.
AB  - BACKGROUND: Breast cancer is a common disease in our community and its incidence
      is increasing. As a result of the improvements in community awareness and
      introduction of screening, patients are being diagnosed with earlier breast
      cancer and with a higher incidence of pre-invasive disease. Improvements in
      radiology, often coupled with minimally invasive diagnostic modalities, have
      lessened the requirement for open diagnostic biopsies and also reduced the number
      of operations for benign breast disease. METHODS: An audit of the surgical
      workload at Prince of Wales/Prince Henry Hospitals and Tamworth Base Hospital was
      conducted to document and compare the above changes in the metropolitan and rural
      settings. This study was conducted between 1987 and 1996 to assess the effect of
      screening and improved technology over a 10-year period. RESULTS: The study found
      that a high percentage of malignant lesions are being diagnosed by fine-needle
      aspiration biopsy (FNAB) with a corresponding reduction in open biopsy rate at
      the Prince of Wales Hospital. There is a smaller percentage of benign operations
      in both settings with a reduction of equal proportion. The reporting of the
      pathology specimens has markedly improved at both institutions. There has been a
      reduction in the number of patients having modified radical mastectomy and there
      has been a corresponding increase in breast conservation surgery especially at
      the Prince of Wales/Prince Henry Hospitals, although there was an unexpectedly
      high incidence of breast conservation surgery at Tamworth Base Hospital in 1987.
      In 1996 the rates of breast conservation surgery were the same in both hospitals.
      CONCLUSIONS: There are minimal differences in the quality of surgical care being
      offered to patients at the Tamworth Base Hospital compared with the Prince of
      Wales Hospital and both institutions are within reach of the accepted best
      management practices available.

PMID- 10075356
TI  - An evaluation of trauma team leader performance by video recording.
AB  - BACKGROUND: Team leader performance in trauma resuscitations was assessed using a
      published system to assess the utility of video recording and to assess the
      current early management of trauma at The Royal Melbourne Hospital, Melbourne,
      Australia. METHODS: Fifty trauma resuscitations were videotaped over a 21-month
      period. Each videotape was assessed by an emergency physician. RESULTS: The team
      leader was an emergency physician in 37 resuscitations, an emergency medicine
      registrar in eight and a surgical registrar in five. The mean team leader score
      was 68.5 +/- 8.5 (range 45-78, maximum possible 80). The average time to primary
      survey completion was 3.3 +/- 1.7 min, second phase of resuscitation up to and
      including chest radiography 14.1 +/- 8.5 min, to completion of secondary survey
      and announcement of overall plan 30 +/- 20 min. Frequent deficiencies are
      documented. Problems with videotaping included forgetting/lack of motivation to
      start taping, forgetting to turn on the sound, difficulty discerning size of
      cannulae and logistical problems with only one cubicle outfitted for videotaping.
      Advantages included lack of intrusion into the resuscitation, increased vigilance
      by team members aware of the possibility of taping, ability to assess tapes at
      leisure and team leader performance in after-hours resuscitations. CONCLUSIONS:
      Video recording is a useful method for the assessment of team member performance
      in trauma resuscitations. Deficiencies in resuscitation technique can be
      identified and fed back to those involved. Medico-legal issues have not proved to
      be a barrier to the use of the technique. A reliable method of starting taping is
      needed.

PMID- 10075357
TI  - Transhiatal versus Ivor-Lewis oesophagectomy: is there a difference?
AB  - INTRODUCTION: Curative oesophageal resection for carcinoma may be carried out by
      either the transhiatal or the Ivor-Lewis transthoracic technique. The aims of
      this study were to compare the morbidity, 30-day mortality and long-term survival
      of the two techniques in the treatment of oesophageal carcinoma and to provide
      data to calculate the sample sizes for a prospective randomized trial. METHODS:
      Results from 44 series published between January 1986 and December 1996 were
      reviewed. Thirty-three papers reported results on 2675 patients having
      transhiatal (THO) and 29 papers reported results on 2808 patients having Ivor
      Lewis oesophagectomy (ILO). RESULTS: The two groups were comparable in terms of
      age, sex and stage of the disease. There was no apparent difference in
      postoperative morbidity between the two groups with respect to respiratory
      complications (24% for THO, 25% for ILO), cardiovascular complications (12.4% for
      THO, 10.5% for ILO), wound infection (8.8% for THO, 6.2% for ILO) and chylothorax
      (2.1% for THO, 3.4% for ILO). The transhiatal group appeared to have a higher
      incidence of anastomotic leaks (16% for THO, 10% for ILO), anastomotic strictures
      (28% for THO, 16% for ILO) and recurrent laryngeal nerve injuries (11.2% for THO,
      4.8% for ILO). The 30-day mortality was 6.3% for transhiatal and 9.5% for Ivor
      Lewis oesophagectomy. Overall long-term survival at 5 years was similar (24% for
      THO, 26% for ILO). CONCLUSIONS: The surgical approach to oesophagectomy was not
      an important determinant of morbidity and long-term survival in patients with
      oesophageal carcinoma. Transhiatal oesophagectomy was associated with a higher
      incidence of anastomotic complications and recurrent laryngeal nerve injury. Ivor
      Lewis oesophagectomy had a higher mortality. In order to demonstrate a
      significant difference in morbidity or long-term survival between the two
      techniques 3100 patients would be required in each arm of a prospective
      randomized trial.

PMID- 10075358
TI  - Good outcome from surgery for ampullary tumour.
AB  - BACKGROUND: Ampulla of Vater tumours are rare but usually resectable. There is
      debate as to the better surgical approach between the standard radical procedure,
      which provides adequate resection margins, and local resection, which may carry a
      lower mortality. This study reports the 16-year experience of a specialist unit
      with these tumours, and compares our results with that of recently published
      series. METHOD: A retrospective review of patients admitted with an ampullary
      tumour to the Hepatobiliary and Pancreatic Surgery Unit, Royal Adelaide Hospital,
      Adelaide, Australia, between January 1981 and April 1997. RESULTS: Twenty-five
      patients (13 men, 12 women) of median age 65 years were admitted with an
      ampullary tumour to the unit during this period. The most common presentation was
      obstructive jaundice. Multiple endoscopic biopsy was found to be very reliable in
      distinguishing between benign and malignant tumours. Five patients, all male, had
      benign neoplasms: three adenomas, one carcinoid and one gangliocytic
      paraganglioma. Transduodenal local excision was performed in four patients. One
      patient had a Whipple procedure resulting in the only in-hospital death at 3
      months. Twenty patients had adenocarcinoma, of which 13 patients had a
      pancreaticoduodenectomy, two local excisions, two palliative bypasses, two were
      unfit for surgery and one declined surgery. The resectability rate was 88%, with
      no operative mortalities. The 5-year actuarial survival of patients who underwent
      radical resection was 49%. CONCLUSIONS: Proximal pancreaticoduodenectomy,
      preferably a pylorus-preserving procedure, is safe and effective in the treatment
      of ampullary carcinoma, with low operative mortality and good long-term survival.
      Local resection is only recommended for small benign tumours and for patients who
      may be unfit for radical surgery.

PMID- 10075359
TI  - Abdominal surgery in the older Crohn's population.
AB  - BACKGROUND: The surgical literature perceives that the elderly cohort of Crohn's
      patients may have increased risk with surgery. METHODS: A retrospective review
      and prospective database analysis of all patients with histologically proven
      Crohn' s disease who had a laparotomy at a single Sydney teaching hospital were
      performed. The last laparotomy of each patient was included in the analysis for
      morbidity and mortality to assess whether an older cohort was at an increased
      risk. RESULTS: A total of 156 patients had 298 laparotomies for
      histopathologically proven Crohn's disease. The frequency distribution of age at
      last laparotomy was bimodal, and the statistically determined cut-off age between
      younger and older cohorts was 55 years. Thirty-three patients were older than 55
      years. There was no difference in duration of symptoms before first diagnosis
      (older, 17 months vs younger, 25 months), previous number of Crohn's operations
      (42.4 vs 39.8%), or duration of known Crohn's disease. Isolated large bowel
      disease was more common in the elderly cohort (42.4 vs 18.7%, chi2 = 8.09, P <
      0.01). Small bowel and ileocaecal resections were more common in the younger
      cohort (72.4 vs 51.6%, chi2 = 5.19, P < 0.025). There was one death in each
      cohort (overall mortality 1.3%) and anastomotic leak rates (defined as the number
      of leaks per number of patients with anastomoses), were 4.3% (older) vs 5.3%
      (younger) despite frank sepsis present in 21.2% of all subjects at the time of
      surgery. The older group had more cardiac (18.2 vs 0.8%, P < 0.001) and
      respiratory complications (18.2 vs 2.4%; P = 0.0003) and a longer mean but not
      median postoperative hospital admission. CONCLUSIONS: In conclusion, clinical
      features and presentation are similar in the older and younger Crohn's patients
      having a laparotomy. However, in the older patient there is a greater likelihood
      of large bowel disease, ileocaecal resection is done less commonly, there is a
      higher risk of minor cardiopulmonary postoperative complications, but with
      similar mortality and anastomotic leak rates to the younger patient.

PMID- 10075360
TI  - Pyogenic liver abscess: a review of 10 years' experience in management.
AB  - BACKGROUND: Over the past 15 years, diagnostic and interventional radiology
      techniques have allowed accurate localization of liver abscesses and image-guided
      percutaneous drainage. This review examines whether these technical advances
      improve clinical results and discusses the selection of treatment for patients
      with liver abscesses. METHODS: Ninety-eight patients were treated for pyogenic
      liver abscess (PLA) at the Royal Prince Alfred Hospital, Sydney, between January
      1987 and June 1997. The hospital records were examined and clinical presentation,
      laboratory, radiological and microbiological findings were recorded. Associations
      between these findings and failure of initial non-operative management were
      determined using odds ratios with 95% confidence intervals. Independent
      predictors were then determined by logistic regression. This analysis was
      repeated to determine factors associated with mortality. RESULTS: Cholelithiasis
      and previous hepatobiliary surgery were the most frequently identifiable causes
      of PLA, each responsible in 15 patients. All 98 patients were treated with
      intravenous antibiotics and in 13 patients this was the only therapy. Of the
      remaining 85 patients, six proceeded straight to laparotomy and 79 had
      percutaneous drainage, of whom 15 required subsequent laparotomy. Factors
      predicting failure of initial non-operative management were unresolving jaundice,
      renal impairment secondary to clinical deterioration, multiloculation of the
      abscess, rupture on presentation and biliary communication. The overall hospital
      mortality rate was 8%. CONCLUSION: Pyogenic liver abscess remains a disease with
      significant mortality. Image-guided percutaneous drainage is appropriate
      treatment for single unilocular PLA. Surgical drainage is more likely to be
      required in patients who have abscess rupture, incomplete percutaneous drainage
      or who have uncorrected primary pathology.

PMID- 10075361
TI  - Role of abdominal drains in perforated duodenal ulcer patients: a prospective
      controlled study.
AB  - BACKGROUND: Duodenal ulcer perforation is a common emergency in south India, with
      about 100-120 cases being treated at Jawaharalal Institute of Post Graduate
      Medical Education and Research each year. The routine to date has been to leave
      two tube drains: one in the Morrison's pouch and one in the pelvis after omental
      patch closure. This study was conducted to test the efficacy and safety of drain
      usage routinely after duodenal ulcer perforation closure with Roscoe Graham
      omental patch technique. METHODS: In this prospective controlled study, 44
      patients formed the test group (without drains) and 75 patients formed the
      control group (with abdominal drainage). Only patients of perforated duodenal
      ulcer closed with Roscoe Graham omental patch technique were included in the
      study. The incidence of postoperative fever, wound infection, time for return of
      bowel function and duration of hospital stay were noted. Details of drainage
      noted were the mean amount of daily drainage, mean time of drain removal and
      occurrence of drain-related complications. Peritoneal fluid, wound discharges,
      drain tips and drain wounds were cultured. Abdominal ultrasound was performed in
      all patients in the second postoperative week or if earlier indicated to detect
      intra-abdominal collections. RESULTS: It was found that there was no difference
      in incidence or duration of postoperative pyrexia, return of bowel function or
      postoperative hospital stay between the two groups. Routine use of drains was not
      effective in preventing postoperative fluid collection nor in decreasing the
      incidence of intra-abdominal abscesses. The migration of bacteria from the
      exterior to the peritoneal cavity via the drain was also demonstrated. Drains
      were found to cause morbidity including intestinal obstruction. CONCLUSION: The
      routine use of drains was found to be neither safe nor effective in patients of
      perforated duodenal ulcer treated by omental patch closure.

PMID- 10075362
TI  - A prospective randomized trial evaluating the haemodynamic role of incompetent
      calf perforating veins.
AB  - AIM: This study was undertaken to determine the haemodynamic effect of
      incompetent calf perforating veins in patients with uncomplicated varicose veins
      and long saphenous incompetence. METHODS: Thirty-eight limbs from 35 patients
      were studied. All patients had uncomplicated varicose veins with both long
      saphenous and calf perforator incompetence on duplex ultrasonography. Patients
      were randomized to have incompetent calf perforators ligated or left intact, in
      addition to saphenofemoral junction ligation, strip of long saphenous vein to
      knee and stab avulsion of any visible varicosities in the leg. Patients were
      assessed with air plethysmography pre-operatively and 3 months postoperatively.
      RESULTS: Superficial venous surgery improved venous volume, venous filling index
      and ejection fraction in the patient cohort. No significant haemodynamic
      difference was demonstrated between the two groups of patients who were
      randomized. CONCLUSIONS: At present, the results of this study do not support the
      use of routine perforator ligation during superficial surgery for uncomplicated
      varicose veins.

PMID- 10075363
TI  - The use of spiral computed tomographic angiography for the assessment of living
      kidney donors.
AB  - BACKGROUND: Recent reports suggest that spiral computed tomographic (CT)
      angiography can replace conventional angiography and intravenous urography for
      the assessment of potential kidney donors. The purpose of this study is to assess
      the accuracy of spiral CT in potential kidney donor workup. METHODS: Over a
      period of 1 year, from December 1995 to December 1996, 16 consecutive potential
      renal donors had intravenous pyelography, percutaneous transfemoral angiography
      with selective renal angiography and spiral CT angiography. The spiral CT and
      renal angiograms were assessed independently by two radiologists. The number of
      renal arteries, presence or absence of renal artery stenoses and associated
      parenchymal abnormalities were assessed. RESULTS: A total of 39 renal arteries
      were detected. Conventional transverse scans viewed in a cine loop format
      detected all 39 vessels, while the maximum intensity projection and shaded
      surface display demonstrated only 37. All 39 vessels were detected by the
      catheter angiography. With the exception of one potential donor with
      fibromuscular dysplasia, 15 donors were accepted. There was 100% accuracy between
      the two methods of visualization for the renal arteries. A simple renal cyst was
      noted in both spiral CT and conventional angiogram, while another had gallstones
      in spiral CT. CONCLUSIONS: Spiral CT angiography performed as an outpatient
      procedure is less invasive, less expensive, and provides good images of the
      arterial and venous anatomy. It has the potential to replace conventional
      catheter angiography and intravenous pyelogram in the assessment of potential
      renal donors.

PMID- 10075364
TI  - Risk factors for ankle fracture requiring operative fixation.
AB  - BACKGROUND: Ankle fractures are common and expensive injuries, particularly the
      injuries that require operative intervention. However, epidemiological research
      on the causative factors is sparse. This study aims to identify the groups at
      risk of ankle fracture requiring operative fixation, and to suggest directions
      for further study. METHODS: The clinical data on 336 patients with ankle
      fractures admitted to an urban hospital in New Zealand in 1994 were reviewed.
      Statistical analysis was carried out on the 252 patients with ankle fractures
      requiring operative fixation. RESULTS: Those at highest risk of ankle fracture
      are young male rugby players and middle-aged women who sustain injury while
      walking. Young males have a similar incidence of AO Type B and C fractures, while
      Type B fractures predominate strongly in older women. CONCLUSIONS: The groups at
      risk of ankle fracture requiring operative fixation, and the activities
      predisposing these groups to injury have been identified. More work is required
      to define the specific risk factors and biomechanical mechanisms that lead to
      these debilitating injuries.

PMID- 10075365
TI  - Blood lipid profile in ischaemia reperfusion injury.
AB  - BACKGROUND: Lipid components are considered to play an important role in
      ischaemia reperfusion injury although the mechanism of their action remains
      unknown. Accumulation of lipid metabolites in ischaemic tissues is a consistent
      observation, but exactly how these lipids are cleared from the tissues by the
      circulating blood during reperfusion is still open to speculation. In the present
      study, levels of blood lipids (fatty acids, phospholipids, triglycerides,
      cholesterol, lysolecithin and lysolecithin platelet activating factor (lyso PAF))
      and the enzyme phospholipase A2 were determined in an experimental animal model
      (dogs) of ischaemic reperfusion injury. METHODS: The injury was induced by 4 h of
      aortic clamping followed by 2 h of reperfusion (unclamping). Blood samples were
      collected before clamping and at predetermined time intervals (0, 15, 60 and 120
      min) after the release of clamp. The lipid contents were analysed and compared
      with sham-treated control dogs. RESULTS: The results showed significantly
      elevated levels of triglycerides and phospholipase A2, during ischaemia and
      reperfusion in experimental animals indicating tissue damage in the ischaemic
      phase continuing into the reperfusion phase and the risk of systemic damage from
      these toxic substances. Total fatty acid content in the circulating blood showed
      decreasing trends during the same time interval, which suggested possible reduced
      clearance of accumulated fatty acids from the affected tissues. Serum
      cholesterol, phospholipids, lyso PAF and lysolecithin did not show any
      significant variation compared with control dogs. CONCLUSIONS: It is possible
      that the delayed clearance of fatty acids may be due to the presence of fatty
      acids binding proteins in the ischaemic tissue, which trap these fatty acids in
      the tissues during ischaemic reperfusion injury. The prolonged retention of the
      accumulated fatty acids in the tissues in association with elevated triglycerides
      and phospholipase A2 activity may contribute to ischaemia reperfusion injury.

PMID- 10075366
TI  - 'Stab and Split': a 'bloodless' and 'scarless' skin incision technique for minor
      surgery.
AB  - The 'stab and split' skin incision technique was applied to children requiring
      minor surgery. A small stab incision was made on a skin crease and split open
      with mosquito forceps. After the surgical procedure was completed, the wound was
      closed in layers with a subcuticular suture to the skin. In all cases, splitting
      caused virtually no blood loss because subcutaneous veins were left intact, and
      the wounds healed well, especially in infants. 'Stab and split' is an effective
      alternative incision technique for minor surgery in younger children.

PMID- 10075367
TI  - Improved percutaneous insertion of long-term central venous catheters in
      children: the 'shrug' manoeuvre.
AB  - BACKGROUND: Surgical central venous access in children usually requires open
      exposure of the internal jugular vein or one of its tributaries. The percutaneous
      route has the potential advantages of a reduced rate of wound infection, superior
      cosmesis and reduced operating time. We report our modifications to the
      percutaneous approach that facilitate the application of this technique to
      children over the age of 12 months. METHODS: The dilator and peel-away sheath of
      the introducer set should be inserted into the subclavian vein under fluoroscopic
      control. Elevation of the ipsilateral shoulder assists passage of the peel-away
      sheath and subsequently the catheter from the subclavian vein into the superior
      vena cava. RESULTS: This technique has been used successfully to establish
      surgical central venous access in the majority of children at the Women's and
      Children's Hospital, Adelaide, South Australia, over a 3-year period.
      CONCLUSIONS: With the modifications described this technique may be safely
      applied to the paediatric age group.

PMID- 10075368
TI  - Paediatric surgical training: comment.

PMID- 10075369
TI  - Paediatric surgical training: comment.

PMID- 10075370
TI  - Craniofacial resection of anterior skull base tumours: comment.

PMID- 10075371
TI  - Symphysiotomy for pelvic access in difficult extirpative surgery.

PMID- 10075372
TI  - Adult incarcerated right-sided Bochdalek hernia.

PMID- 10075373
TI  - Presternal extension of a malignant thyroid swelling.

PMID- 10075374
TI  - Malignant peripheral nerve sheath tumour of the tongue.

PMID- 10075375
TI  - Mucinous adenocarcinoma of renal pelvis and villous adenoma of bladder after a
      caecal augmentation of bladder.

PMID- 10075376
TI  - Summary of notifiable diseases, United States, 1997.

PMID- 10075377
TI  - Prevention of recurrent pulmonary edema in patients with bilateral renovascular
      disease through renal artery stent placement.
AB  - Pulmonary edema and congestive heart failure (both referred to here as PE) have
      been reported to be complications of bilateral renal artery stenosis or
      unilateral stenosis in a solitary functioning kidney (both referred to as BRAS).
      The goals of this study were to determine whether a history of PE was more common
      in patients with BRAS than in those with unilateral stenosis and a normal
      contralateral kidney (URAS), and whether recurrent PE could be prevented by renal
      artery stent placement. We evaluated 90 consecutive patients with renovascular
      disease who were treated with percutaneous renal artery stent placement. History
      and clinical follow-up were obtained through chart review and phone contact with
      referring physicians. Mean follow-up was 18.4 months after stent placement.
      Twenty-three of 56 (41%) subjects with BRAS had a history of PE before
      revascularization, compared with four of 34 (12%) subjects with URAS (P = .05).
      Twenty-five of the 27 patients with history of PE had adequate clinical follow
      up. Seventeen of the 22 (77%) subjects with BRAS and history of PE had no further
      PE after stent placement in one or both renal arteries. The five BRAS subjects
      with recurrent PE after stent placement had evidence of stent thrombosis or
      restenosis. In contrast, only one of three (33%) URAS subjects with a history of
      PE remained free of PE after stent placement. We conclude that PE is a common
      complication of BRAS, but not of URAS. In patients with BRAS, recurrent PE can be
      prevented by successful stent placement in one or both renal arteries.

PMID- 10075378
TI  - Effect of L-arginine infusion on systemic and renal hemodynamics in hypertensive
      patients.
AB  - This study was designed to compare the renal endothelial function in patients
      with essential hypertension and normal renal function with that in hypertensive
      patients with renal insufficiency. We studied the effects of L-arginine (500
      mg/kg intravenously over 30 min) on renal hemodynamics in 30 normotensive control
      subjects, 32 patients with mild to moderate essential hypertension who had normal
      renal function, and seven hypertensive patients with renal insufficiency who had
      a serum creatinine concentration >2.0 mg/mL and a glomerular filtration rate <50
      mL/min/1.48 m2. L-Arginine infusion similarly reduced the mean blood pressure
      between the three groups (normotensive: -9.7% +/- 0.7%, hypertensives with normal
      renal function: -10.2% +/- 0.8%, and hypertensives with renal insufficiency: 
      8.2% +/- 1.3%). The L-arginine-induced decrease in renal vascular resistance was
      smaller in essential hypertensive patients than in normotensive subjects (-11.0%
      +/- 2.2 v -19.8% +/- 2.1%, P <.05). However, L-arginine had no effect on the
      renal vascular resistance in hypertensive patients with renal insufficiency (1.6%
      +/- 4.8%). Urine nitrite/nitrate levels in response to L-arginine significantly
      increased in the three groups in the following order: patients with renal
      insufficiency (47% +/- 15%), essential hypertensive patients (87% +/- 10%), and
      normotensive subjects (129% +/- 12%). The glomerular filtration rate was
      unaffected by L-arginine in normotensive and essential hypertensive patients
      (3.1% +/- 2.4% and 4.2% +/- 2.5%), but significantly decreased in hypertensive
      patients with renal insufficiency (-13.7% +/- 6.1%). These findings suggest that
      the ability of the L-arginine-nitric oxide-cGMP pathway to relax the renal
      vascular tone may be impaired in essential hypertensive patients and more
      markedly blunted in hypertensive patients with renal insufficiency, in parallel
      with increasing serum creatinine concentrations.

PMID- 10075379
TI  - Microalbuminuria and hypertension in nondiabetic Japanese men.
AB  - To investigate the relationship between microalbuminuria and hypertension in
      nondiabetic subjects, we selected 245 Japanese men aged 35 to 69 years on the
      basis of the results of a 75 g oral glucose tolerance test. Prevalence of
      hypertension (blood pressure levels > or =140/90 mm Hg or treatment of
      hypertension) in microalbuminuria-positive (0.03 to 0.3 g/d) subjects was
      significantly higher than that in microalbuminuria-negative (<0.03 g/day)
      subjects. Also, the significant increase of levels of triglycerides, serum uric
      acid, and area of plasma insulin were recognized in microalbuminuria-positive
      subjects. Urinary albumin was significantly related to both systolic and
      diastolic blood pressure in a manner independent of these relevant factors,
      including area of insulin. With regard to renal functions, creatinine clearance
      of microalbuminuria positive subjects was significantly increased and fractional
      excretion of sodium of microalbuminuria-positive subjects was significantly
      decreased as compared with those of microalbuminuria-negative subjects. In
      normotensive subjects, serum uric acid, which is known to be related to sodium
      handling at renal tubules of microalbuminuria-positive subjects, was
      significantly higher than those of microalbuminuria negative subjects as well as
      triglycerides and area of insulin, without the differences of the levels of blood
      pressure and BMI. Therefore, it is suspected that microalbuminuria is a renal
      facet of insulin resistance, and a predictor value of hypertension.

PMID- 10075380
TI  - Angiotensin II subtype-1 receptor antagonists improve hemodynamic and renal
      changes without affecting glucose metabolisms in genetic rat model of non-insulin
      dependent diabetes mellitus.
AB  - The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non
      insulin-dependent diabetes mellitus (NIDDM). We investigated whether treatment
      with an angiotensin II (ANGII) subtype-1 receptor antagonist delays the onset of
      NIDDM and attenuates diabetic nephropathy in the OLETF rat. OLETF rats fed a
      regular chow were treated with ANGII subtype-1 receptor antagonists (E4177 or
      TA606) for 22 weeks. Hemodynamic changes, glucose metabolism, and the effects on
      diabetic nephropathy were examined. Systolic blood pressure increased in OLETF
      rats in an age-dependent manner. OLETF rats exhibited increases in plasma
      concentrations of glucose and insulin and developed glucosuria at the age of 28
      weeks. The changes in glucose metabolism were associated with proteinuria and an
      increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG).
      Morphologic investigation revealed nodular lesions in glomeruli in the OLETF
      rats. The ANGII receptor antagonist treatment abolished the blood pressure
      elevation. However, the treatment did not affect plasma glucose and insulin
      levels and did not significantly reduce glucosuria. Nodular lesions in glomeruli
      were not improved by the treatment. However, the receptor antagonists
      significantly reduced proteinuria and urinary NAG excretion. Multivariate
      analyses revealed that proteinuria was determined by systolic blood pressure,
      lipid metabolism, and glucose levels in plasma. ANGII subtype-1 antagonism does
      not improve glucose metabolism in the OLETF rat model of NIDDM, which has
      abnormalities in the glucose-uptake system. Blood pressure elevation and part of
      the proteinuria associated with NIDDM depends on the renin-angiotensin system
      rather than glucose metabolisms per se.

PMID- 10075381
TI  - Comparison of the effects of AT1 receptor blockade and angiotensin converting
      enzyme inhibition on atherosclerosis.
AB  - Angiotensin converting enzyme (ACE) inhibitors reduce the development of
      atherosclerosis in hypercholesterolemic animals across a wide range of species.
      Although the mechanism for these effects has not been well delineated, it has
      been assumed generally that both angiotensin II suppression and interference with
      the breakdown of bradykinin are involved. To determine whether angiotensin II
      receptor blockade provides similar effects as those observed with ACE inhibition,
      we examined the influence of irbesartan, an AT1 receptor antagonist, on aortic
      atherosclerosis in Watanabe heritable hyperlipidemic rabbits using the identical
      protocol that was employed in our earlier studies involving ACE inhibitors. At a
      dose of irbesartan (30 mg/kg/day), which was selected because it appeared to
      block most of the pressor effects of infused angiotensin in rabbits, no effect on
      atherosclerosis was observed. However, a higher dose of irbesartan (75 mg/kg/day)
      caused reductions in blood pressure and aortic atherosclerosis similar to those
      seen in earlier studies with ACE inhibitors. The decrease in aortic intimal
      surface involvement with irbesartan was from 38.9 +/- 3.8% in controls to 24.1 +/
      3.0% in the treated group (P < .01). Aortic cholesterol content was also
      significantly reduced in those animals (P < .02). The findings indicate that
      suppression of the renin-angiotensin system by AT1 receptor blockade in a
      genetically hypercholesterolemic rabbit model causes comparable inhibition of
      aortic atherosclerosis as that achieved by ACE inhibition, and that a mild
      reduction of blood pressure induced by both classes of agents may contribute to
      their antiatherosclerotic action in this model.

PMID- 10075382
TI  - Determinants of circadian blood pressure rhythm in essential hypertension.
AB  - It has been postulated that the lack of nocturnal blood pressure fall in patients
      called nondippers is associated with more serious end organ damages by
      hypertension than in dippers whose blood pressure falls during the night.
      Recently, we found that sodium restriction shifted circadian rhythm of blood
      pressure from that of a nondipper to a dipper in patients with essential
      hypertension. In the present study, we aimed to clarify these important findings
      from the different approaches, and examined which factors affected the diurnal
      rhythm of blood pressure. A total of 70 patients with essential hypertension were
      maintained on high and low sodium diets for 1 week each. Nocturnal fall in mean
      arterial pressure was calculated in each patient, and, based on multiple
      regression analysis, independent factors affecting this nocturnal fall were
      examined. Thirty-eight patients were classified as non-sodium-sensitive, whereas
      32 were considered sodium sensitive, based on a >10% change in 24-h mean arterial
      pressure by sodium restriction. In all 70 patients, sodium sensitivity of blood
      pressure, as well as an interaction between sodium sensitivity and sodium
      restriction, were identified as independent factors affecting the nocturnal fall.
      In sodium-sensitive types, in addition to sodium restriction, glomerular
      filtration rate was identified, whereas, in non-sodium sensitive types, there was
      no significant factor. Based on multiple regression analysis, the present study
      reached the same important conclusion as our previous findings: namely, that the
      enhanced sodium sensitivity was an independent determinant for the diminished
      nocturnal fall in essential hypertension and that sodium restriction could
      restore the nocturnal decline, especially in patients with enhanced sodium
      sensitivity whose nocturnal decline was diminished. Reduced renal sodium
      excretory capability may be one of the mechanisms involved in nondipping.

PMID- 10075383
TI  - Ca2+ channels of the L-type in peripheral blood lymphocytes of essential
      hypertensives.
AB  - Ca2+ channels of the L-type were assayed in human peripheral blood lymphocytes of
      normotensive control subjects and of essential hypertensives using radioligand
      binding assay techniques. The dihydropyridine Ca2+ channel blocker [3H](+)-PN 200
      110 [isopropyll-4-(2,1,3-benzoxadiazol-4-yl)1,4-dihydro-5-methox ycarbonyl-2,6
      dimethyl-3-pyridine carboxylate] was used as a ligand. [3H](+)-PN 200 110 was
      bound specifically to human peripheral blood lymphocytes in a manner consistent
      with the labeling of Ca2+ channels of the L-type. No significant differences in
      the dissociation constant (Kd), in the maximum density of binding sites (Bmax) or
      in the pharmacological profile of [3H](+)-PN 200 110 binding were found between
      normotensive subjects and different degree essential hypertensives. Analysis of
      the intralymphocytic free Ca2+ concentration did not reveal differences between
      normotensive subjects and essential hypertensives. Although hypertension is
      associated with altered membrane handling of Ca2+, no changes in the expression
      of peripheral blood lymphocyte Ca2+ channels of the L-type or in intralymphocytic
      Ca2+ concentrations were found in essential hypertensives. Human peripheral blood
      lymphocytes therefore cannot represent a peripheral marker of altered Ca2+
      handling in hypertension.

PMID- 10075384
TI  - Effects of isoflavonoids on blood pressure in subjects with high-normal
      ambulatory blood pressure levels: a randomized controlled trial.
AB  - Vegetarian diets lower blood pressure (BP), but attempts to identify dietary
      components responsible have been unsuccessful. Isoflavonoids are commonly
      consumed as part of vegetarian diets. The objective of this study was to assess
      the effect of isoflavonoid supplementation on BP. Fifty-nine subjects with high
      normal range systolic BP completed a randomized, double blind, placebo-controlled
      trial of two-way parallel design and 8 weeks duration. One tablet containing 55
      mg of isoflavonoids, including 30 mg of genistein, 16 mg of biochanin A (a
      genistein precursor), 1 mg of daidzein, and 8 mg of formononetin (a daidzein
      precursor), or one placebo tablet, was taken daily with the evening meal.
      Significant increases in urinary excretion of genistein (5.22 mg/day, 95% CI:
      3.72, 6.72) and daidzein (2.53 mg/day, 95% CI: 1.66, 3.40) were observed in the
      group taking the isoflavonoid supplement. There were no significant changes in
      isoflavonoid excretion in the placebo group. Clinic BP was measured at two
      visits, and ambulatory BP monitoring was performed over one 24-h period, at
      baseline and postintervention. There was no significant difference between
      groups, after adjustment for baseline values, in postintervention clinic supine
      BP (systolic 1.2 mm Hg, 95% CI: -2.3, 4.7; diastolic 0.6 mm Hg, 95% CI: -1.9,
      2.5), clinic erect BP (systolic 1.7 mm Hg, 95% CI: -4.0, 8.4; diastolic 0.4 mm
      Hg, 95% CI: -2.4, 3.2), or 24-h ambulatory BP (systolic -1.4 mm Hg, 95% CI: -4.4,
      1.6; diastolic -0.8 mm Hg, 95% CI: -2.3, 0.7). Adjustment for age, gender, and
      weight change did not alter the result. Therefore, these results do not support
      the hypothesis that isoflavonoids, and genistein in particular, are major
      contributors to the BP lowering effect of vegetarian diets.

PMID- 10075385
TI  - Cold acclimation-induced increase of systolic blood pressure in rats is
      associated with volume expansion.
AB  - To investigate the mechanisms of cold-induced hypertension, the systolic blood
      pressure (SBP) and average daily water consumption were measured weekly in 6
      month-old male Wistar rats; they were subsequently acclimated to thermoneutrality
      (26 degrees C for 7 weeks), to cold temperature (6 degrees C for 9 weeks), and
      then again reacclimated to 26 degrees C for 5 weeks. Circulating plasma volume
      and whole blood viscosity were measured in subgroups of rats at the end of
      acclimation to 26 degrees C after 2 days, after 1, 6, and 8 weeks of cold, and
      after 2 and 5 weeks of rewarming. The control values obtained at the end of
      thermoneutral period were: SBP = 130.8 +/- 18.6 mm Hg, plasma volume = 41.9 +/-
      4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 +/- 0.48
      cps, and daily water consumption = 42.25 +/- 16.81 mL. After 48 h of cold
      exposure there was almost a 50% increase in plasma volume that persisted to a
      lesser degree throughout the whole period of cold exposure (P < .05). After 2
      weeks of cold exposure the daily water consumption increased and SBP began to
      increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the
      control level (P < .001) and was accompanied by a 25% increase in whole blood
      viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was
      56.8 +/- 9.51 mL/ kg and the whole blood viscosity was 8.0 +/- 1.79 cps at the
      22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and
      increased whole blood viscosity persisted, whereas the increased daily water
      consumption and expanded plasma volume returned to normal. Therefore, the
      acclimation to cold is accompanied by the development of a volume-associated
      hypertension, which is sustained after rewarming without volume expansion.

PMID- 10075386
TI  - Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h
      study.
AB  - The influence of acute sleep deprivation during the first part of the night on 24
      h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to
      moderate hypertensive patients. According to a crossover design, they were
      randomized to have either sleep deprivation or a full night's sleep 1 week apart,
      during which they were monitored with ABPM. Urine samples for analysis of
      nocturnal urinary excretion of norepinephrine were collected. During the sleep
      deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were
      higher in comparison with those recorded during the routine workday, the
      difference being more pronounced during the nighttime (P < .01). Urinary
      excretion of norepinephrine showed a significant increase at night during sleep
      deprivation (P < .05). Blood pressure and heart rate significantly increased in
      the morning after a sleep-insufficient night (P < .05). These data suggest that
      lack of sleep in hypertensive patients may increase sympathetic nervous activity
      during the night and the following morning, leading to increased blood pressure
      and heart rate. This situation might represent an increased risk for both target
      organ damage and acute cardiovascular diseases.

PMID- 10075387
TI  - Urinary sodium and potassium profile of blacks and whites in relation to
      education in two different geographic urban areas. TOMHS Research Group.
      Treatment of Mild Hypertension Study.
AB  - The high Na/low K environment of modern society is related to the genesis of
      hypertension and stroke. There is prior evidence of racial, geographical, and
      social class differences in Na and K intake and blood pressure. Baseline data
      from the Treatment of Mild Hypertension Study (TOMHS) was used to assess urinary
      Na and K excretion profiles by race, clinic geographic area, and education.
      Participants were adult black and white hypertensive patients from the
      Birmingham, Alabama, and Chicago, Illinois, area. Level of education was
      categorized as: less than college graduate and college graduate or more. Two
      overnight urine samples were collected and analyzed for Na and K at entry from
      154 blacks and 281 whites. The urinary Na:K ratio was significantly higher in
      both blacks (5.1 v 3.8, P < .001) and whites (4.1 v 3.4, P < .005) in Birmingham
      compared with Chicago. This was primarily due to the lower excretion of urinary K
      in blacks (12.8 v 16.9 mmol/8 h, P < .01) and whites (14.0 v 16.5 mmol/8 h, P <
      .01). The highest urinary Na:K ratio was observed in blacks in Birmingham with
      lower education level; urinary Na excretion was high in blacks with a lower
      education level in both cities. No such differences were seen in whites. Although
      TOMHS was not population-based, these findings suggest the possibility that
      potassium intake among persons with stage 1 hypertension is related to geographic
      area in both blacks and whites, and sodium intake is inversely related to
      education level in blacks.

PMID- 10075388
TI  - Reduced bcl-2 concentrations in hypertensive patients after lisinopril or
      nifedipine administration.
AB  - In 30 patients with essential hypertension and 30 healthy control subjects, we
      evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that
      can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in
      normotensive subjects. The increase in pressure due to a cold pressor test caused
      a further increase in blood bcl-2 concentrations, in both hypertensive and
      normotensive subjects. Treatment of hypertensive patients with hypotensive drugs
      caused a reduction in bcl-2 concentrations, which was more marked after
      administration of lisinopril than of nifedipine. The results suggest that
      concentrations of bcl-2 are increased in patients with hypertension, which could
      be an important factor in cell proliferation underlying posthypertensive vascular
      remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing
      bcl-2 concentrations, with potentially beneficial effects on vascular
      modifications in patients with hypertension.

PMID- 10075389
TI  - Prospective, double-blind, seemingly ignored clinical trials.

PMID- 10075390
TI  - Problems with interpreting the data in Kassler-Taub et al's article comparing
      irbesartan and losartan.

PMID- 10075391
TI  - Therapeutic implications of calcium intake in hypertension: more analyses, a
      little progress, and a different approach.

PMID- 10075392
TI  - The influence of dietary and nondietary calcium supplementation on blood
      pressure: an updated metaanalysis of randomized controlled trials.
AB  - We updated our previous systematic review of the effect of supplemental calcium
      on blood pressure. We extended our previous searches on MEDLINE and EMBASE to May
      1997 and examined citations from relevant articles. We contacted the authors of
      eligible trials to ensure the accuracy and completeness of data, and to identify
      unpublished trials. We included any study in which investigators randomized
      hypertensive or normotensive people to calcium supplementation or alternative
      therapy and measured blood pressure for at least 2 weeks. In addition to 32
      trials included in the prior metaanalysis, 10 new trials contributed to this
      metaanalysis. Two pairs of independent reviewers abstracted data and assessed the
      validity of the study data according to six quality criteria. We calculated the
      differences in blood pressure change between the calcium supplementation and
      control groups and pooled the estimates with each trial weighted with the inverse
      of the variance using a random effects model. The predictors of blood pressure
      reduction that we examined included method of supplementation, baseline blood
      pressure, and the methodologic quality of the studies. The pooled analysis shows
      a reduction in systolic blood pressure of -1.44 mm Hg (95% confidence interval 
      2.20 to -0.68; P < .001) and in diastolic blood pressure of -0.84 mm Hg (95%
      confidence interval -1.44 to -0.24; P < .001). We found statistically significant
      heterogeneity of results across trials (P < or = .02), which persisted when we
      looked at the nondietary trials alone, but not when we restricted our analysis to
      dietary trials. Although there was a trend toward larger effects with dietary
      interventions, none of the possible mediators of blood pressure reduction
      explained differences in treatment effect. We conclude that calcium
      supplementation leads to a small reduction in systolic and diastolic blood
      pressure. The effect of supplemental calcium in the diet is at least as great as
      nondietary supplementation.

PMID- 10075393
TI  - The "calcium antihypertension theory".

PMID- 10075394
TI  - Dietary calcium and blood pressure.

PMID- 10075395
TI  - The role of dietary calcium in hypertension: a hierarchical overview.
AB  - The role of calcium in clinical hypertension can be best understood by a
      hierarchical model in which the blood pressure effects of a dietary signal depend
      on alterations of hormonal systems specific for that signal. These alterations
      mediate both the cellular recognition of these signals as well as the resultant
      clinical responses to them. In the case of both dietary calcium and dietary salt,
      these systems appear to include calcium regulating hormones having direct,
      calcium-dependent vasoactive properties, and which are linked to the activity of
      the renin-angiotensin system. Altered salt and calcium intake exert reciprocal
      linked effects on these hormone systems and on blood pressure. These reflect
      altered cellular calcium uptake from the extracellular space, salt-induced
      calcium hormones stimulating and calcium-induced suppression of these hormones
      inhibiting extracellular calcium uptake. Among normotensive individuals, this is
      associated with a reciprocal calcium-dependent suppression or stimulation of
      renin secretion, respectively, resulting in an offsetting decreased or increased
      angiotensin II-mediated release of calcium into the cytoplasm from intracellular
      stores. Hence, no significant change in cytosolic free calcium or, consequently,
      in blood pressure usually results from increasing or decreasing dietary salt or
      calcium intake. However, whether due to genetic or other environmental factors as
      yet undefined, the metabolic "set point" of plasma renin activity in some
      subjects is already suppressed, or, alternatively, is unresponsive to the above
      hormonally mediated dietary mineral variations. Under these circumstances,
      increases in dietary salt will cause cytosolic free calcium and thus blood
      pressure to rise, whereas increased dietary calcium in these very same "salt
      sensitive" subjects will offset the effect of salt, and lower pressure in these
      individuals. This analysis suggests that although increasing oral calcium intake
      to achieve at least current nutritional standards is entirely appropriate,
      uniform recommendations for all hypertensives to further increase or decrease
      dietary calcium or salt may be inappropriate and will obscure those for whom
      these maneuvers are particularly relevant.

PMID- 10075396
TI  - Risky single-occasion drinking amongst young people--definition, correlates,
      policy, and intervention: a broad overview of research findings.
AB  - Risky single-occasion drinking (RSOD) has dire consequences upon health and well
      being including unplanned pregnancies, sexually transmitted diseases such as
      HIV/AIDS, crime, and car accidents. The prevalence of RSOD among young people is
      alarming. Despite this, as yet, a review of existing literature on RSOD amongst
      young people is lacking. This article will provide an overview of this area of
      research focusing on the definition of RSOD, its prevalence among young people,
      health and behavioural effects of RSOD, the perceived risk of RSOD among young
      people, and interventions to reduce RSOD in young people. In addition,
      recommendations are made for health educators interested in reducing the
      incidence of RSOD in young people.

PMID- 10075397
TI  - The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal
      to clinical studies.
AB  - Since its discovery nearly 40 years ago, gamma-hydroxybutyric acid (GHB) has
      attracted several waves of scientific interest due to new developments in the
      knowledge of its mechanisms of action and ideas for its potential use in clinical
      practice. Its effects have been claimed to treat different psychiatric
      conditions, but over time its use has become limited to a few specific situations
      (e.g. sedating patients in non-painful surgical procedures and narcolepsy). New
      interest in the drug derives from its potential use in the treatment of
      alcoholism. Recent studies demonstrated a marked effect of the substance in
      suppressing ethanol (ETOH) withdrawal symptoms and in reducing craving for
      alcohol, compared to other available drugs. However, GHB has to be given under
      very careful supervision because of its side-effects, including the risk of abuse
      and dependence and possible interference with the metabolic pathways of
      endogenous GHB and ETOH. This short review discusses these and related issues and
      we hope that it will stimulate further interest in GHB.

PMID- 10075398
TI  - The impact of Alcohol and Alcoholism among substance abuse journals.
AB  - This article concerns the question of journal impact factor and other
      bibliometric indicators made available by the Institute for Scientific
      Information in their Journal Citation Report for 1996. The impact factors of
      journals within the subject category 'substance abuse' are listed along with
      total citations, immediacy indices, and cited half-lives. The relationship
      between cited and citing journals is discussed with the main focus on the data
      available for Alcohol and Alcoholism. Some of the problems and limitations of
      bibliometric measures of productivity are dealt with, especially when these are
      used to evaluate the work of individual scientists. Although bibliometric
      measures are easy to compute, they become difficult to interpret, such as when
      dealing with collaborative research and the problem posed by multiple authorship.
      The need to adjust impact factors and citation counts for the number of co
      authors in a paper becomes important when credit has to be attributed to one
      individual from a multi-author paper. This is often necessary in connection with
      grant applications and when making decisions about academic promotion and tenure.
      The impact factor of Alcohol and Alcoholism has increased steadily over the past
      5 years, even after adjusting for the number of self-citations, which resulted in
      an even greater increase in impact. However, the impact factors of substance
      abuse journals are generally low, compared with disciplines such as immunology,
      genetics, and biochemistry. Some suggestions are made for increasing the impact
      factors of substance abuse journals if this is considered necessary. But instead
      of paying attention to the impact factor of a journal, scientists should give
      more consideration to the speed and efficiency of the editorial handling of their
      manuscripts and particularly to the quality and timeliness of the peer review.

PMID- 10075399
TI  - Correlation between increases in dihydropyridine binding in vivo and behavioural
      signs of ethanol withdrawal in mice.
AB  - Increased ligand binding to dihydropyridine receptors in the central nervous
      system after chronic ethanol consumption is thought to contribute to the
      withdrawal syndrome. Previous studies demonstrated such changes when the binding
      was measured in vitro, which, as the receptors are voltage-sensitive, may not
      accurately reflect the binding in vivo. In the present study, dihydropyridine
      binding was measured in vivo in mice, after intravenous administration of the
      radioligand. The aim was to determine whether there was any correlation between
      such binding and measurements of behavioural hyperexcitability at different times
      during the withdrawal phase and after two different methods of alcohol
      administration. Measurements were made of the binding in vivo of
      [3H]nitrendipine, at intervals after withdrawal from chronic ethanol
      administration, and of the severity of withdrawal as measured by response to
      gentle handling. An increase in the in vivo binding to [3H]nitrendipine was seen
      after cessation of chronic ethanol consumption by liquid diet. The binding was
      significantly increased at 4 h, when the behavioural changes were maximal, but
      not immediately after withdrawal, when the responses to handling were unchanged.
      By 24 h after cessation of the ethanol treatment, no differences in the binding
      were found, compared with control values; at this time the withdrawal
      hyperexcitability had ceased. When alcohol was given chronically by inhalation,
      the in vivo dihydropyridine binding was increased at 3 h from withdrawal of the
      ethanol, the time of maximal behavioural hyperexcitability, but no change was
      seen 30 min after withdrawal, when no changes in the ratings of behaviour were
      found. There was a significant positive correlation in individual mice between
      the ratings of handling-induced behaviour at the 3 h interval and the amount of
      in vivo binding. These data support the hypothesis that the sites labelled by
      [3H]nitrendipine play an important role in withdrawal hyperexcitability.

PMID- 10075400
TI  - Involvement of nicotinic acetylcholine receptors in the regulation of alcohol
      drinking in Wistar rats.
AB  - The aim of the present study was to determine if nicotinic acetylcholine
      receptors (nAChRs) might be involved in the regulation of alcohol intake by
      Wistar rats. A non-selective nAChR agonist, nicotine, and a non-competitive nAChR
      antagonist, mecamylamine, were tested in alcohol-preferring Wistar rats
      maintained on a limited access (4 h/24 h) to ethanol (10%, v/v). In addition, the
      effects of nicotine and mecamylamine on intake of standard laboratory chow were
      studied in a separate control experiment. Nicotine (0.1-0.6 mg/kg, s.c.)
      decreased ethanol consumption, but had no effect on food intake. In contrast,
      mecamylamine (1-3 mg/kg, s.c.) did not alter ethanol drinking even at the dose (3
      mg/kg) which significantly decreased food intake. These results suggest that
      activation of nAChRs may selectively reduce ethanol consumption in outbred Wistar
      rats.

PMID- 10075401
TI  - Ciprofloxacin administration decreases enhanced ethanol elimination in ethanol
      fed rats.
AB  - Many colonic aerobic bacteria possess alcohol dehydrogenase (ADH) activity and
      are capable of oxidizing ethanol to acetaldehyde. Accordingly, some ingested
      ethanol can be metabolized in the colon in vivo via the bacteriocolonic pathway
      for ethanol oxidation. By diminishing the amount of aerobic colonic bacteria with
      ciprofloxacin treatment, we recently showed that the bacteriocolonic pathway may
      contribute up to 9% of total ethanol elimination in naive rats. In the current
      study we evaluated the role of the bacteriocolonic pathway in enhanced ethanol
      metabolism following chronic alcohol administration by diminishing the amount of
      gut aerobic flora by ciprofloxacin treatment. We found that ciprofloxacin
      treatment totally abolished the enhancement in ethanol elimination rate (EER)
      caused by chronic alcohol administration and significantly diminished the amount
      of colonic aerobic bacteria and faecal ADH activity. However, ciprofloxacin
      treatment had no significant effects on the hepatic microsomal ethanol-oxidizing
      system, hepatic ADH activity or plasma endotoxin level. Our data suggest that the
      decrease in the amount of the aerobic colonic bacteria and in faecal ADH activity
      by ciprofloxacin is primarily responsible for the decrease in the enhanced EER in
      rats fed alcohol chronically. Extrahepatic ethanol metabolism by gastrointestinal
      bacteria may therefore contribute significantly to enhanced EER.

PMID- 10075402
TI  - Enhancing the identification of excessive drinkers on medical wards: a 1-year
      follow-up study.
AB  - This paper describes a 1-year follow-up study examining whether hospital ward
      doctors and nurses continue to take quantitative alcohol histories and provide
      brief intervention to problem drinkers on general medical wards after the
      introduction of a simple protocol. Regular training in the use of this protocol
      was stipulated in the annual service contract between the Health Authority and
      the Hospital Trusts. Improvements in staff practice persisted at 1-year follow
      up, although it fell from a peak at an earlier phase of the study. The positive
      role of state purchasers of health services in sustaining improvements in
      clinical practice is discussed.

PMID- 10075403
TI  - Urban-rural comparisons of drink-driving behaviour among late teens: a
      preliminary investigation.
AB  - A preliminary study was conducted to examine the nature and extent of urban-rural
      differences in self-reported drinking and driving among youths in Western
      Australia. A total of 102 youths aged 17, 18 and 19 years were surveyed via a
      random street sampling technique about their alcohol consumption and drink
      driving behaviour. Analyses indicated that urban youths had a significantly
      higher level of self-reported drink-driving behaviour than their rural
      counterparts. Males indicated a higher level of self-reported drink-driving
      behaviour than females. This article also provides a review and summary of youth
      drink-driving literature with special focus on urban-rural comparisons.

PMID- 10075404
TI  - Alcohol consumption profile by time in middle-aged men: a longitudinal study
      based on three different diagnostic instruments.
AB  - This longitudinal study aimed at comparing aggregate measures of heavy or problem
      drinking and their variations across time among the same subjects. We examined
      middle-aged men participating in a health survey over a 5-year interval. Of the
      133 consecutive men in the whole age group interviewed as 40-year-olds in 1989,
      114 were reached and re-interviewed in 1994. Alcohol consumption was measured by
      self-report, Malmo-modified Michigan Alcoholism Screening Test (Mm-MAST), and
      serum carbohydrate-deficient transferrin (CDT). Self-reported alcohol consumption
      decreased with years (142 vs 105 g/week, P = 0.01), as did CDT (16.9 vs 14.4 U/l,
      P = 0.02), but there was no change in the Mm-MAST results. There was no
      significant difference in the number of heavy drinkers (either Mm-MAST score > or
      = 3, or by self-reported alcohol consumption > or = 280 g/week, or by CDT > or =
      20 U/l) at 40 and 45 years of age (37 and 47% respectively). At the individual
      level, alcohol consumption both increased and decreased with age. At 45 years of
      age 5/114 (4%) of the men reported that they had increased their alcohol
      consumption by more than 80 g/week and 25/114 (22%) said that they had reduced
      their drinking by the same amount. The remaining 84 (74%) reported drinking the
      same amount as 5 years earlier (+/- 80 g/week). This indicates that alcohol
      drinking habits are not stable in middle age. Most heavy drinkers in both age
      groups were detected by Mm-MAST and this proportion increased with age while the
      proportion of positive self-reports and CDTs decreased. Thus, the social
      consequences, measured here by the Mm-MAST, may be more readily experienced with
      years even at smaller consumption levels.

PMID- 10075405
TI  - Ethyl glucuronide--a marker of alcohol consumption and a relapse marker with
      clinical and forensic implications.
AB  - Ethyl glucuronide (EtG) is a non-volatile, water-soluble, direct metabolite of
      ethanol that can be detected in body fluids and hair. We investigated urine and
      serum samples from three patient groups: (1) 33 in-patients in acute alcohol
      withdrawal; (2) 30 detoxified in-patients (treated for at least 4 weeks) from a
      'motivation station'; and (3) 43 neuro-rehabilitation patients (non-alcoholics;
      most of them suffering from stroke, traumatic brain injury, Parkinson's disease
      etc.) using gas chromatography/mass spectrometry (GC/MS) with deuterium-labelled
      EtG as the internal standard and additionally in the second group of patients
      using liquid chromatography (LC/MS-MS). We found no correlation between the
      concentration of EtG in urine at hospitalization and the blood-ethanol
      concentration (r = 0.17), the time frame of detection (r = 0.5) or the total
      amount of clomethiazole required for the treatment of withdrawal symptoms (r =
      0.28). In four out of 30 in-patients from the 'motivation station'--where neither
      clinical impression nor routine laboratory findings gave indications of relapse-
      concentrations of EtG in urine ranged between 4.2 and 196.6 mg/l. EtG
      concentrations in urine of between 2.89 and 23.49 mg/l were found in seven out of
      43 neuro-rehabilitation patients using GC/MS. The GC/MS and the LC/MS-MS results
      showed a correlation of 0.98 with Pearson's correlation test and 1.0 with
      Spearman's correlation test. We suggest that EtG is a marker of alcohol
      consumption that can be detected for an extended time period after the complete
      elimination of alcohol from the body. When used as a relapse marker with a
      specific time frame of detection intermediate between short- and long-term
      markers, EtG fills a clinically as well as forensically important gap. Its
      specificity and sensitivity exceed those of all other known ethanol markers.

PMID- 10075406
TI  - Alcohol consumption, alcohol-related problems, problem drinking, and
      socioeconomic status.
AB  - In general, a lower socioeconomic status (SES) is related to a lower health
      status, more health problems, and a shorter life expectancy. Although causal
      relations between SES and health are unclear, lifestyle factors play an
      intermediate role. The purpose of the present study was to obtain more insight
      into the relation between SES, alcohol consumption, alcohol-related problems, and
      problem drinking, through a general population survey among 8000 people in
      Rotterdam. Odds ratios were calculated using educational level as independent,
      and alcohol consumption, alcohol-related problems, and problem drinking as
      dependent variables. Abstinence decreased significantly by increasing educational
      level for both sexes. For men, excessive drinking, and notably very excessive
      drinking, was more prevalent in the lowest educational group. For women, no
      significant relation between educational level and prevalence of excessive
      drinking was found. After controlling for differences in drinking behaviour,
      among men the prevalence of 'psychological dependence' and 'social problems' was
      higher in intermediate educational groups, whereas prevalence of 'drunkenness'
      was lower in intermediate educational groups. For women, a negative relation was
      found between educational level and 'psychological dependence'; prevalence of
      'symptomatic drinking' was higher in the lowest educational group. Prevalence of
      problem drinking was not related to educational level in either sex. It is
      concluded that differences exist between educational levels with respect to
      abstinence, but only limited differences were found with respect to excessive
      drinking. Furthermore, there is evidence for higher prevalences of alcohol
      related problems in lower educational levels, after controlling for differences
      in drinking behaviour, in both sexes.

PMID- 10075407
TI  - Abstracts of the 11th International Conference on Alcohol. Held in Liverpool, UK,
      on 19-22 April 1998.

PMID- 10075408
TI  - A twisted tale: the origin and evolution of motility and chemotaxis in
      prokaryotes.

PMID- 10075409
TI  - ISP-4 and CWBP52 are proteins encoded by the same gene in Bacillus subtilis.

PMID- 10075410
TI  - Evidence that halogenated furanones from Delisea pulchra inhibit acylated
      homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal
      from its receptor protein.
AB  - Acylated homoserine lactone (AHL)-mediated gene expression controls phenotypes
      involved in colonization, often specifically of higher organisms, in both marine
      and terrestrial environments. The marine red alga Delisea pulchra produces
      halogenated furanones which resemble AHLs structurally and show inhibitory
      activity at ecologically realistic concentrations in AHL bioassays. Evidence is
      presented that halogenated furanones displace tritiated OHHL [N-3-(oxohexanoyl)-L
      homoserine lactone] from Escherichia coli cells overproducing LuxR with potencies
      corresponding to their respective inhibitory activities in an AHL-regulated
      bioluminescence assay, indicating that this is the mechanism by which furanones
      inhibit AHL-dependent phenotypes. Alternative mechanisms for this phenomenon are
      also addressed. General metabolic disruption was assessed with two-dimensional
      PAGE, revealing limited non-AHL-related effects. A direct chemical interaction
      between the algal compounds and AHLs, as monitored by 1H NMR spectroscopy, was
      shown not to occur in vitro. These results support the contention that furanones,
      at the concentrations produced by the alga, can control bacterial colonization of
      surfaces by specifically interfering with AHL-mediated gene expression at the
      level of the LuxR protein.

PMID- 10075411
TI  - Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle
      mechanism.
AB  - The growth of budding yeast, Saccharomyces cerevisiae, was inhibited in medium
      containing 25 microM farnesol (FOH). The FOH-treated cells were still viable, and
      were characterized by a transition from budded to unbudded phase as well as a
      significant loss of intracellular diacylglycerol (DAG). FOH-induced growth
      inhibition could be effectively prevented by the coaddition of a membrane
      permeable DAG analogue which can activate yeast protein kinase C (PKC). However,
      yeast cell growth was not initiated upon addition of the PKC activator when the
      cells had been pretreated with FOH for 20 min. The failure in cell growth
      recovery was believed to be due to a signalling-mediated cell cycle arrest in FOH
      pretreated cells. Differential display analysis demonstrated that the expression
      of cell cycle genes encoding DNA ligase (CDC9) and histone acetyltransferase
      (HAT2) was strongly repressed in FOH-treated cells. Repression of the expression
      of these genes was effectively cancelled when cells were grown in medium
      supplemented with DAG. The authors propose an interference with a
      phosphatidylinositol-type signalling which is involved in cell cycle progression
      as a cause of FOH-induced growth inhibition in yeast cells.

PMID- 10075412
TI  - Reconstitution of a bacterial/plant polyamine biosynthesis pathway in
      Saccharomyces cerevisiae.
AB  - Polyamine synthesis in most organisms is initiated by the decarboxylation of
      ornithine to form putrescine via ornithine decarboxylase (ODC). Plants, some
      bacteria and some fungi and protozoa generate putrescine from arginine, via
      arginine decarboxylase (ADC) and agmatine ureohydrolase (AUH) or agmatine
      iminohydrolase. A polyamine-requiring strain of Saccharomyces cerevisiae with a
      mutation in the gene encoding ODC was transformed with plasmids bearing genes
      encoding Escherichia coli ADC and AUH. Transformants regained the ability to grow
      in the absence of exogenous polyamines and contained enzyme activities consistent
      with the presence of both prokaryotic enzymes. Similar results were obtained when
      a plasmid containing a gene encoding oat (Avena sativa L.) ADC was substituted
      for the E. coli gene. These data demonstrate the successful complementation of a
      yeast biosynthetic polyamine synthesis defect by genes encoding an alternative
      pathway found in bacteria; they also show that plant ADC can substitute for the
      bacterial enzyme in this pathway. The recombinant yeast provides a tool for the
      study of the functional properties of these enzymes and for discovery of
      compounds that specifically inhibit this pathway.

PMID- 10075413
TI  - Down-regulation of the expression of PKC1 and SRB1/PSA1/VIG9, two genes involved
      in cell wall integrity in Saccharomyces cerevisiae, causes flocculation.
AB  - The cell wall integrity determinants PKC1 and SRB1/PSA1/VIG9 of Saccharomyces
      cerevisiae were expressed under the control of the tightly regulated promoter
      pMET3. Substitution of the cell-cycle-regulated SRB1/PSA1 native promoter with
      pMET3 led to faster cell growth, larger cell volumes, and a twofold reduction of
      the steady-state SRB1/PSA1 mRNA level. In addition, the new pattern of expression
      of SRB1/PSA1 resulted in a dominant flocculation phenotype at all phases of batch
      growth. By contrast, expression of PKC1 from pMET3 increased the flocculation
      capacity of cells only at stationary phase. Methionine-mediated repression of
      either PSA1/SRB1 or PKC1 resulted in enhanced cell clumping. Cells in which both
      these genes had been replaced with their respective pMET3-regulated cassettes
      were highly flocculent under both expression and repression conditions. These
      results suggest that greater exposure of flocculin on the cell surface, caused by
      either cell wall distortion (through depletion of Pkc1p) or aberrant regulation
      of mannosylation (through constitutive production of Srb1p), results in an
      increased flocculation ability.

PMID- 10075414
TI  - Transcription of the pcbAB, pcbC and penDE genes of Penicillium chrysogenum AS-P
      78 is repressed by glucose and the repression is not reversed by alkaline pHs.
AB  - Glucose repressed transcription of the penicillin biosynthesis genes pcbAB, pcbC
      and penDE when added at inoculation time to cultures of Penicillium chrysogenum
      AS-P-78 but it had little repressive effect when added at 12 h and no effect when
      added at 24 or 36 h. A slight increase in the expression of pcbC and penDE (and
      to a smaller extent of pcbAB) was observed in glucose-grown cultures at pH 6.8,
      7.4 and 8.0 as compared with pH 6.2, but alkaline pHs did not override the strong
      repression exerted by glucose. Transcription of the actin gene used as control
      was not significantly affected by glucose or alkaline pHs. Repression by glucose
      of the three penicillin biosynthetic genes was also observed using the lacZ
      reporter gene coupled to each of the three promoters in monocopy transformants
      with the constructions integrated at the pyrG locus. Glucose repression of the
      three genes encoding enzymes of penicillin biosynthesis therefore appears to be
      exerted by a regulatory mechanism independent from pH regulation.

PMID- 10075415
TI  - Replication regions from plant-pathogenic Pseudomonas syringae plasmids are
      similar to ColE2-related replicons.
AB  - Many strains of the phytopathogen Pseudomonas syringae contain mutually
      compatible plasmids that share extensive regions of sequence homology and
      essential replication determinants. The replication regions of two compatible
      large plasmids involved in virulence or pathogenicity, pPT23A from P. syringae
      pv. tomato strain PT23 and pAV505 from P. syringae pv. phaseolicola strain
      HRI1302A, were isolated. DNA sequencing of the origins of replication revealed
      homologous ORFs, designated ORF-Pto and ORF-Pph, respectively. Both ORFs are 1311
      bp long and encode peptides of 437 amino acids with predicted molecular masses of
      48259 (Pto) and 48334 (Pph) Da. Expression of the two ORFs in Escherichia coli
      produced peptides of 50 kDa (Pto) and 56 kDa (Pph). The predicted peptides showed
      an overall identity of 897 %, being highly conserved from residues 1 to 373, but
      showing considerable variation in their C-terminal regions (50% identity over the
      last 64 aa). The two ORFs had significant similarity with the putative
      replication protein from plasmid pTiK12 of Thiobacillus intermedius and other
      CoIE2-related plasmids. However, both peptides were 100 residues longer than any
      of the known CoIE2-related rep sequences. Subcloning of fragments from the
      replication region of pPT23A revealed the presence of at least three
      incompatibility determinants, designated IncA, IncB and IncC. Partial sequencing
      of the region downstream of ORF-Pto revealed homology to the ru/AB genes,
      involved in UV resistance, from plasmid pPSR1. It is proposed that the
      replication origin of pPT23A serves as the prototype of a family of related
      plasmids.

PMID- 10075416
TI  - Ultrastructure of surface components of Streptococcus gallolytics (S. bovis)
      strains of differing virulence isolated from pigeons.
AB  - Virulence of Streptococcus gallolyticus (S. bovis) strains isolated from pigeons
      is associated with the presence of the extracellular proteins A, T1, T2 and T3.
      Based on the presence or absence of these proteins, six supernatant-phenotypes
      are distinguished. Experimental infection studies have indicated that strains
      belonging to the A-T1, A+T1, A+T2 and A+T3 groups are highly virulent for
      pigeons, strains belonging to the A-T3 groups are moderately virulent and A-T2
      strains are of low virulence. In this study the surface structure of 15 pigeon S.
      gallolyticus strains representing high, moderate and low virulence supernatant
      phenotypes was examined by electron microscopy. The presence of capsular material
      was determined by transmission electron microscopy after polycationic ferritin
      labelling and immunostabilization. Capsules from cells labelled with polycationic
      ferritin were usually thicker than those from cells exposed to antiserum. The
      capsule of the virulent strains had a regular, continuous appearance whilst
      irregularity of the capsule was a characteristic of the low virulence A-T2
      strains. Negative staining revealed the presence of fimbriae in all strains
      belonging to the high virulence A-T1, A+T1, A+T2 and A+T3 supernatant groups and
      in one strain of the moderately virulent A-T3 group. The fimbriae were thin,
      flexible structures with a diameter of approximately 3-4 nm and a length of up to
      700 nm. Fimbriae as described above were absent in two other A-T3 strains
      examined and in the low virulence A-T2 strains. Results from this study indicate
      that morphological differences in surface structure exist among virulent and low
      virulence pigeon S. gallolyticus strains, and that the capsule and/or fimbriae
      are possibly involved in virulence.

PMID- 10075417
TI  - Antigenic characterization and cytolocalization of P35, the major Mycoplasma
      penetrans antigen.
AB  - Mycoplasma penetrans is a mycoplasma with unique morphology, recently identified
      in urine samples collected from HIV-infected patients. This mycoplasma has been
      found to be statistically associated with HIV infection, and to be cytopathic in
      vitro. The dominant antigen recognized during natural and experimental infections
      is an abundant lipoprotein, P35, which, upon extraction, segregates in the Triton
      X-114 detergent phase. It is used as the basis of M. penetrans-specific
      serological assays. Although mycoplasma lipoproteins, including M. penetrans P35,
      are the main antigens recognized by the host humoral immune response, very little
      is known about the nature of the epitopes involved. Immunoelectron microscopy
      revealed that all P35 is exposed at the cell surface and is distributed all over
      the membrane. P35 linear B-epitopes were mapped by an ELISA approach based on a
      set of overlapping peptides covering the entire mature polypeptide. The
      immunoreactivity of the peptides was first tested with sera from immunized
      animals. The dominant B-epitopes were found at the C- and N-terminal regions, in
      partial agreement with algorithmic predictions. Patient sera were evaluated with
      the same assay. Only some reacted with linear epitopes whereas others did not,
      indicating the importance of P35 nonsequential epitopes. Statistical analysis of
      the results allowed the definition of a set of peptides which were clearly
      immunodominant. Finally, the P35-encoding gene was modified by in vitro
      mutagenesis to allow the production and purification of a recombinant protein
      (rP35delta0) in Escherichia coil. The antigenicity of rP35delta0 was tested by
      Western blotting and compared to that of another recombinant product, rP35delta3,
      a truncated P35 polypeptide. Although rP35delta0 reacted with the M. penetrans
      seropositive patient sera tested, rP35delta3 was only immunoreactive with one of
      six sera. This result confirmed that P35-nonsequential epitopes dominate during
      M. penetrans infection. Our results have important implications for the
      understanding of lipoprotein antigenicity during mycoplasma infections. In
      addition, the P35-derived immunodominant synthetic peptides defined in this
      study, as well as the purified rP35delta0, provide the antigenic material for the
      necessary improvement of M. penetrans serological assays.

PMID- 10075418
TI  - Streptococcus mutans ffh, a gene encoding a homologue of the 54 kDa subunit of
      the signal recognition particle, is involved in resistance to acid stress.
AB  - The ability of Streptococcus mutans, a bacterial pathogen associated with dental
      caries, to tolerate rapid drops in plaque pH (acidurance), is considered an
      important virulence factor. To study this trait, Tn917 mutants of S. mutans
      strain JH1005 which display acid sensitivity have been isolated and partially
      characterized. In this paper, the characterization of one of these mutants, AS17,
      is reported. Preliminary sequence analysis revealed that the transposon insertion
      in AS17 occurred in the intergenic region of a two-gene locus which has been
      named sat for secretion and acid tolerance. This locus displays a high degree of
      homology to the ylxM-ffh operon of Bacillus subtilis. The sat+ locus was cloned
      by complementation of a conditional Escherichia coli ffh mutant with an S. mutans
      genomic library. Sequencing of the complementing clone identified the intact ylxM
      and ffh genes as well as a partial ORF with homology to the proUlopuAC gene of B.
      subtilis which encodes the binding protein of the ProU/OpuA osmoregulated glycine
      betaine transport system. RNA dot blot experiments indicated steady-state levels
      of ffh mRNA in the mutant that were approximately eightfold lower compared to
      parental levels. This suggests a partial polar effect of the sat-1::Tn917
      mutation on ffh expression. Upon acid shock (pH 5), wild-type ffh mRNA levels
      were found to increase approximately four- to eightfold compared to unstressed
      (pH 7.5) levels. Mutant levels remained unaltered under the same conditions.
      Experiments designed to investigate the origins of the acid-sensitivity of the
      mutant revealed a lack of an acid-adaptive/tolerance response. Assays of proton
      extruding ATPase (H+/ATPase) specific activity measured with purified membranes
      derived from acid-shocked AS17 showed twofold lower levels compared to the parent
      strain. Also, AS17 was found to be unable to ferment sorbitol although it was
      able to grow in glucose and a variety of other sugar substrates. These findings
      suggest that Ffh may be involved in the maintenance of a functional membrane
      protein composition during adaptation of S. mutans to changing environmental
      conditions.

PMID- 10075419
TI  - The Salmonella typhi melittin resistance gene pqaB affects intracellular growth
      in PMA-differentiated U937 cells, polymyxin B resistance and lipopolysaccharide.
AB  - Salmonella typhi is the causative agent of typhoid fever in humans. A cell
      culture based assay involving the human monocyte macrophage cell line U937 has
      been developed to examine S. typhi invasion and survival. An S. typhi PhoP-
      (null) mutant was shown to be restricted in net growth in phorbol myristate
      acetate (PMA) differentiated U937 (PMA-U937) cells, and an S. typhi PhoPc
      (constitutive) mutant showed a defect in invasion. Neither of the phoP/Q mutants
      were growth impaired in HeLa cells, however the PhoPc mutant was impaired in
      invasion. As opposed to what was found for S. typhi, Salmonella typhimurium wild
      type, PhoP- and PhoPc mutants grew equally well in PMA-U937 cells, indicating
      that the PhoP(-)-mediated net growth restriction in the PMA-U937 cells was S.
      typhi specific. An S. typhi mutation, pqaB::MudJ, recently shown to be a PhoP
      activated locus, was shown to have a net growth defect in PMA-U937 cells.
      Sequencing of the S. typhipqaB gene revealed it had 98% identity to the fifth
      gene in a S. typhimurium PmrA/B regulated operon necessary for 4-aminoarabinose
      lipid A modification and polymyxin B resistance. The pqaB locus was regulated by
      PmrA/B (whose activity is modulated by PhoP-PhoQ) and the pqaB transposon mutant
      was sensitive to polymyxin B. The lipopolysaccharides (LPS) of S. typhi and S.
      typhimurium wild-type, PhoP- and PhoPc mutants, were compared by SDS-PAGE and
      silver staining. Differences in the LPS profile between the two Salmonella
      species were observed, and shown to be affected differently by the PhoPc
      mutation. Additionally, the pqaB::MudJ mutation affected S. typhi LPS. The
      effects on LPS may have ramifications for the difference between S. typhi and S.
      typhimurium infection of hosts.

PMID- 10075420
TI  - Cloning, mutation and distribution of a putative lipopolysaccharide biosynthesis
      locus in Campylobacter jejuni.
AB  - A region encoding ORFs with homology to known lipopolysaccharide (LPS)
      biosynthesis genes was isolated from two strains of Campylobacter jejuni. One of
      the strains produces LPS, but the second strain is reported to produce only
      lipooligosaccharide (LOS) and therefore lacks the O-chain. The two strains shared
      six predicted ORFs, but an additional ORF, orfE, of unknown function was
      identified in the LOS-producing strain. Mutation of the shared wbeE (rfbE)
      homologue (orfF) or deletion of five of the seven genes reduced core reactivity
      with specific antiserum without affecting O-chain production. Mutation of either
      the capD homologue (orfG) or the unique orfE had no detectable effect on LOS or
      LPS production. The presence or absence of orfE in 36 isolates of C. jejuni did
      not correlate with LOS/LPS phenotype or serotype. However, after insertion of
      orfE into a LPS-producing orfE-negative strain the O-chain ladder was no longer
      detectable on Western blots. We were not able to disrupt the wbaP (rfbP)
      homologue (orfC) in C jejuni.

PMID- 10075421
TI  - Characterization of the recD gene of Neisseria gonorrhoeae MS11 and the effect of
      recD inactivation on pilin variation and DNA transformation.
AB  - Pilin antigenic variation in Neisseria gonorrhoeae may result following
      intrachromosomal recombination between homologous pil genes. Despite extensive
      study, recA is the only previously characterized gene known to be involved in
      this process. In this study, the gonococcal recD gene, encoding one subunit of
      the putative RecBCD holoenzyme, was characterized and its role in pilin variation
      assessed. The complete recD gene of N. gonorrhoeae MS11 was cloned and its
      nucleotide sequence determined. The gonococcal recD gene complemented a defined
      Escherichia coli recD mutant, based on plaque formation of bacteriophage lambda
      and the restoration of ATP-dependent nuclease activity. Inactivation of the
      gonococcal recD gene had no measurable effect on cell viability or survival
      following UV exposure, but did decrease the frequency of DNA transformation
      approximately threefold. The frequency at which non-parental pilin phenotypes
      were spawned was 12-fold greater in MS11 recD mutants compared with the parental
      MS11 rec+ strain. Similar results were obtained using recD mutants that were not
      competent for DNA transformation. Complementation of the MS11 recD mutant with a
      wild-type recD gene copy restored the frequency of pilin phenotypic variation to
      approximately wild-type levels. The nucleotide changes at pilE in the recD
      mutants were confined to the variable regions of the gene and were similar to
      changes previously attributed to gene conversion.

PMID- 10075422
TI  - Identification of Haemophilus influenzae Rd transformation genes using cassette
      mutagenesis.
AB  - Genes required for natural transformation of Haemophilus influenzae Rd were
      identified by a cassette mutagenesis protocol consisting of the following steps:
      random insertional mutagenesis, phenotypic screening, sequencing of genome
      sequence tags from the DNA flanking the insertion in the selected mutants and
      comparison of genome sequence tags to genomic sequence data. The cassette
      mutagenesis screen for transformation genes resulted in five distinct mutant
      classes, two of which have been identified in previous studies. Insertions in the
      three newly identified loci interrupted genes with predicted protein products
      homologous to a type IV pilin-like protein biogenesis operon, drug-efflux
      transporters and a phospholipid-biosynthesis enzyme. The most significant finding
      of this screen is the requirement for type IV pilin-like proteins in genetic
      transformation of H. influenzae. These surface structures are utilized for DNA
      uptake in a number of Gram-positive and Gram-negative bacteria, and appear to be
      the common component among the systems for DNA binding.

PMID- 10075423
TI  - Molecular evidence for the existence of additional members of the order
      Chlamydiales.
AB  - Respiratory tract infections in man may be caused by several members of the genus
      Chlamydia and also by two Chlamydia-like strains, 'Simkania negevensis' (Z-agent)
      and 'Parachlamydia acanthamoebae' (Bng). To facilitate diagnostic procedures a
      PCR assay able to detect all known Chlamydiaceae sequences in one reaction was
      developed. For this purpose, primers were selected to amplify a fragment of the
      16S rRNA gene. Characterization of the amplified fragments was done by
      hybridization with specific probes and by sequencing. PCR assays were carried out
      using DNA isolated from nose/throat specimens or from peripheral blood
      mononuclear cells of patients with respiratory tract infections, and from vessel
      wall specimens of abdominal aneurysms. Six of the 42 nose/throat swab specimens
      analysed yielded strong bands and one yielded a faint band. Three of these bands
      were identified as Chlamydia pneumoniae and one as Chlamydia trachomatis by
      sequencing. Analysis of the three other bands yielded two different new
      sequences. DNA isolated from peripheral blood mononuclear cells of one patient
      yielded a third new sequence. DNA isolated from peripheral blood mononuclear
      cells of four healthy controls was negative. One of the abdominal aneurysm
      specimens also yielded a strong band. Sequencing revealed a fourth new sequence.
      All negative controls included during specimen processing and PCR analysis
      remained negative. The typical secondary structure of microbial 16S genes was
      present in all four new sequences indicating the validity of the sequence data.
      All four new sequences were distinct from other bacteria and clustered together
      with known Chlamydiaceae sequences. Phylogenetic analysis suggested a new
      lineage, separating the four new sequences, 'S. negevensis' and 'P.
      acanthamoebae' from the genus Chlamydia with the four known chlamydial species.
      In conclusion, this study provides evidence for the existence of several new
      members of the order Chlamydiales. Since the source of the Chlamydia-like strains
      has not been identified and serological and/or molecular cross-reactivities may
      be expected, results of identification of infecting recognized organisms should
      be interpreted cautiously.

PMID- 10075424
TI  - The effects of hydrostatic pressure on ribosome conformation in Escherichia coli:
      and in vivo study using differential scanning calorimetry.
AB  - Differential scanning calorimetry of whole Escherichia coil cells allowed the
      detection in vivo of changes in ribosome conformation. This enabled for the first
      time an analysis of the effects of high hydrostatic pressures on ribosomes in
      living cells. A correlation was observed between loss of cell viability and
      decrease in ribosome-associated enthalpy in cells subjected to pressures of 50
      250 MPa for 20 min. Cell death and ribosome damage were therefore closely related
      phenomena. In pressure-treated cells, the thermogram peak temperatures decreased,
      suggesting that the remaining ribosomes had adopted a less stable conformation.
      During subsequent incubation of the cultures at 37 degrees C, peak temperatures
      and enthalpies gradually increased over a period of 5 h. This change in ribosome
      conformation had no apparent effect on cell survival, as viability continued to
      decrease. The addition of 5 mM MgCl2 before pressure treatment of cells prevented
      the reduction in stability of surviving ribosomes but had no effect on the
      initial loss of enthalpy or on cell viability.

PMID- 10075425
TI  - The osmoprotectant glycine betaine inhibits salt-induced cross-tolerance towards
      lethal treatment in Enterococcus faecalis.
AB  - The response of Enterococcus faecalis ATCC 19433 to salt stress has been
      characterized previously in complex media. In this report, it has been
      demonstrated that this bacterium actively accumulates the osmoprotectant glycine
      betaine (GB) from salt-enriched complex medium BHI. To further understand the
      specific effects of GB and other osmoprotective compounds in salt adaptation and
      salt-induced cross-tolerance to lethal challenges, a chemically defined medium
      lacking putative osmoprotectants was used. In this medium, bacterial growth was
      significantly reduced by increasing concentrations of NaCl. At 0.75 M NaCl, 90%
      inhibition of the growth rate was observed; GB and its structural analogues
      restored growth to the non-salt-stressed level. In contrast, proline, pipecolate
      and ectoine did not allow growth recovery of stressed cells. Kinetic studies
      showed that the uptake of betaines shows strong structural specificity and occurs
      through a salt-stress-inducible high-affinity porter [Km = 3.3 microM; Vmax = 130
      nmol min(-1) (mg protein)(-1); the uptake activity increased 400-fold in the
      presence of 0.5 M NaCl]. Moreover, GB and its analogues were accumulated as non
      metabolizable cytosolic osmolytes and reached intracellular levels ranging from 1
      3 to 1.5 micromol (mg protein)(-1). In contrast to the beneficial effect of GB on
      the growth of salt-stressed cultures of E. faecalis, its accumulation inhibits
      the salt-induced cross-tolerance to a heterologous lethal challenge. Indeed,
      pretreatment of bacterial cells with 0.5 M NaCl induced resistance to 0.3% bile
      salts (survival of adapted cells increased by a factor of 6800). The presence of
      GB in the adaptation medium reduced the acquisition of bile salts resistance 680
      fold. The synthesis of 11 of the 13 proteins induced during salt adaptation was
      significantly reduced in the presence of GB. These results raise questions about
      the actual beneficial effect of GB in natural environments where bacteria are
      often subjected to various stresses.

PMID- 10075426
TI  - Characterization of a prolidase from Lactobacillus delbrueckii subsp. bulgaricus
      CNRZ 397 with an unusual regulation of biosynthesis.
AB  - Lactobacillus delbrueckii subsp. bulgaricus CNRZ 397 (Lb. bulgaricus) is
      characterized by a high level of peptidase activities specific to proline
      containing peptides. A prolidase (PepQ, EC 3.4.13.9) was purified to homogeneity
      and characterized as a strict dipeptidase active on X-Pro dipeptides, except Gly
      Pro and Pro-Pro. The values for Km and Vmax were, respectively, 2.2 mM and 0.33
      mmol min(-1) mg(-1), with Leu-Pro as the substrate. The enzyme exhibited optimal
      activity at 50 degrees C and pH 6.0, and required the presence of Zn2+. Size
      exclusion chromatographies and SDS-PAGE analysis led to the conclusion that this
      prolidase was a homodimer. Antibodies raised against the purified protein allowed
      the detection of PepQ among several Lactobacillus species but not lactococci. The
      pepQ gene and the upstream region were isolated and sequenced. The deduced
      peptide sequence showed that PepQ belongs to the M24 family of metallopeptidases.
      The pepR1 gene is located immediately upstream of pepQ and its product is
      homologous to the transcription factor CcpA, which is involved in catabolite
      repression of catabolic operons from Gram-positive bacteria. The pepR1-pepQ
      intergenic region contains a consensus catabolite-responsive element (CRE) which
      could be a target for PepR1 protein. Moreover, in contrast to other proline
      specific enzymes from Lb. bulgaricus, PepQ biosynthesis was shown to be dependent
      on the composition of the culture medium, but not on the peptide concentration. A
      possible regulation mechanism is discussed.

PMID- 10075427
TI  - The marine cyanobacterium Synechococcus sp. WH7805 requires urease (urea
      amidohydrolase, EC 3.5.1.5) to utilize urea as a nitrogen source: molecular
      genetic and biochemical analysis of the enzyme.
AB  - Cyanobacteria assigned to the genus Synechococcus are an important component of
      oligotrophic marine ecosystems, where their growth may be constrained by low
      availability of fixed nitrogen. Urea appears to be a major nitrogen resource in
      the sea, but little molecular information exists about its utilization by marine
      organisms, including Synechococcus. Oligonucleotide primers were used to amplify
      a conserved fragment of the urease (urea amidohydrolase, EC 3.5.1.5) coding
      region from cyanobacteria. A 5.7 kbp region of the genome of the unicellular
      marine cyanobacterium Synechococcus sp. strain WH7805 was then cloned, and genes
      encoding three urease structural subunits and four urease accessory proteins were
      sequenced and identified by homology. The WH7805 urease had a predicted subunit
      composition typical of bacterial ureases, but the organization of the WH7805
      urease genes was unique. Biochemical characteristics of the WH7805 urease enzyme
      were consistent with the predictions of the sequence data. Physiological data and
      sequence analysis both suggested that the urease operon may be nitrogen-regulated
      by the ntcA system in WH7805. Inactivation of the large subunit of urease, ureC,
      prevented WH7805 and Synechococcus WH8102 from growing on urea, demonstrating
      that the urease genes cloned are essential to the ability of these cyanobacteria
      to utilize urea as a nitrogen source.

PMID- 10075428
TI  - Homologous expression of soluble methane monooxygenase genes in Methylosinus
      trichosporium OB3b.
AB  - An homologous expression system has been developed for soluble methane
      monooxygenase (sMMO) genes from Methylosinus trichosporium OB3b. sMMO-minus
      mutants were previously obtained after marker-exchange mutagenesis, by the
      insertion of a kanamycin-resistance cassette into the mmoX gene of the sMMO
      operon. Complementation of the sMMO-minus genotype was achieved by conjugation
      with broad-host-range plasmids containing the native promoter and sMMO operon
      from Ms. trichosporium OB3b (pVK100Sc and pHM2). In wild-type methanotrophs,
      copper ions present in the growth medium at concentrations greater than 0.25
      microM inhibit transcription of sMMO genes. The stable maintenance of pVK100Sc
      resulted in transconjugant methanotrophs with a decreased sensitivity to copper,
      since expression of sMMO occurred at copper sulphate concentrations of 7.5
      microM. sMMO activity was only detected in soluble extracts after the addition of
      purified sMMO reductase component, which is inhibited by copper ions in vitro.
      This phenomenon could have arisen due to the increased number of sMMO gene copies
      (derived from pVK100Sc) in the cell. Transconjugants obtained from conjugations
      with pHM2 expressed sMMO at copper concentrations of 0-2.5 microM only and sMMO
      activity was not restored by the addition of purified reductase component at
      copper concentrations higher than 2.5 microM. Southern hybridization showed that
      the plasmid had integrated into the chromosome, probably by a single homologous
      recombination event. This is the first report of homologous sMMO expression in a
      methanotroph with enzyme activities that are comparable to the activity reported
      in wild-type strains. This expression system will be useful for site-directed
      mutagenesis of active-site residues of sMMO from Ms. trichosporium OB3b.

PMID- 10075429
TI  - Cytochrome c550 is an essential component of the quinoprotein ethanol oxidation
      system in Pseudomonas aeruginosa: cloning and sequencing of the genes encoding
      cytochrome c550 and an adjacent acetaldehyde dehydrogenase.
AB  - Pseudomonas aeruginosa ATCC 17933 grown aerobically on ethanol produces a soluble
      cytochrome c550 together with a quinoprotein ethanol dehydrogenase. A 3.2 kb
      genomic DNA fragment containing the gene encoding cytochrome c550 was cloned and
      sequenced. Two other complete and two truncated ORFs were also identified. A
      truncated ORF encoding the quinoprotein ethanol dehydrogenase (exaA) was found
      upstream of the cytochrome c550 gene (exaB) and in reverse orientation. An ORF
      encoding a NAD(+)-dependent acetaldehyde dehydrogenase (exaC) was located
      downstream of the cytochrome c550 gene and in the same orientation. Another ORF
      showed similarity to the pqqA gene and a truncated ORF similarity to the pqqB
      gene, both involved in the biosynthesis of the prosthetic group PQQ. The
      organization of these genes was found to be different from the well-studied
      methanol oxidation system in methylotrophic bacteria. The deduced amino acid
      sequence of cytochrome c550 from P. aeruginosa showed some similarity to
      cytochrome c6 of the alga Chlamydomonas reinhardtii and the haem domain of
      quinohaemoprotein alcohol dehydrogenases of acetic acid bacteria, but no
      similarity to the soluble cytochrome cL of the quinoprotein methanol oxidation
      system of methylotrophs could be detected. A mutant of P. aeruginosa with an
      interrupted cytochrome c550 gene was unable to grow on ethanol, which proves that
      cytochrome c550 is an essential component of the ethanol oxidation system in this
      organism.

PMID- 10075430
TI  - Superoxide dismutase and catalase in Photobacterium damselae subsp. piscicida and
      their roles in resistance to reactive oxygen species.
AB  - Photobacterium damselae subsp. piscicida (formerly Pasteurella piscicida) is the
      causative agent of pasteurellosis or pseudotuberculosis in warm water marine
      fish. Enzymes which neutralize reactive oxygen species, produced during aerobic
      metabolism or during respiratory burst in fish macrophages, are important
      virulence factors in many pathogens. This study characterizes a periplasmic
      superoxide dismutase (SOD) and a cytoplasmic catalase in P. damselae.
      Purification and partial amino-terminal sequencing confirmed the SOD to be iron
      cofactored, with a high degree of homology to other bacterial FeSODs. The SOD was
      common to all strains analysed in terms of type, location and activity, whilst
      the catalase varied in activity between strains. The catalase was constitutively
      expressed, but the SOD appeared to be repressed under low oxygen conditions. In
      spite of the presence of a periplasmic SOD, P. damselae was susceptible to
      killing by exogenous superoxide anion generated in a cell-free system. Addition
      of exogenous SOD to this system did not abolish the bactericidal effect; however,
      addition of catalase was protective. These results suggest that lack of
      periplasmic catalase may be implicated in susceptiblity to killing by reactive
      oxygen species.

PMID- 10075431
TI  - Cloning and characterization of the thiD/J gene of Escherichia coli encoding a
      thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine
      kinase/phosphomethylpyrimidine kinase.
AB  - A 1.7 kb DNA fragment isolated from an E. coli genomic library was able to
      complement the thiamin requirement of strains carrying the thiM, thiJ and thiD
      mutations. The three genes encode hydroxyethylthiazole kinase,
      hydroxymethylpyrimidine (HMP) kinase and phosphomethylpyrimidine (HMP-p) kinase,
      respectively. Sequence analysis revealed that the 1.7 kb fragment contained two
      ORFs of 708 bp and 801 bp. The former ORF complemented the thiM mutation and the
      latter ORF both the thiJ and thiD mutations. The latter ORF was cloned into the
      expression vector pET3a, and the encoded protein was purified through three
      successive column chromatographies. The purified protein was able to convert HMP
      to its monophosphate and the monophosphate to its pyrophosphate. These results
      suggest that the two distinct enzyme activities, HMP kinase and HMP-P kinase, are
      indeed a bifunctional enzyme encoded by a single gene, designated thiDIJ.

PMID- 10075432
TI  - Cloning, sequence analysis, expression and inactivation of the Corynebacterium
      glutamicum pta-ack operon encoding phosphotransacetylase and acetate kinase.
AB  - The Corynebacterium glutamicum ack and pta genes encoding the acetate-activating
      enzymes acetate kinase and phosphotransacetylase were isolated, subcloned on a
      plasmid and re-introduced into Corynebacterium glutamicum. Relative to the wild
      type, the recombinant strains showed about tenfold higher specific activities of
      both enzymes. Sequence analysis of a 3657 bp DNA fragment revealed that the ack
      and pta genes are contiguous in the corynebacterial chromosome, with pta upstream
      and the last nucleotide of the pta stop codon (TAA) overlapping the first of the
      ack start codon (ATG). The predicted gene product of pta consists of 329 amino
      acids (Mr 35242), that of ack consists of 397 amino acids (Mr 43098) and the
      amino acid sequences of the two polypeptides show up to 60 %
      (phosphotransacetylase) and 53% (acetate kinase) identity in comparison with
      respective enzymes from other organisms. Northern (RNA) blot hybridizations using
      pta- and ack-specific probes and transcriptional cat fusion experiments revealed
      that the two genes are transcribed as a 2.5 kb bicistronic mRNA and that the
      expression of this operon is induced when Corynebacterium glutamicum grows on
      acetate instead of glucose as a carbon source. Directed inactivation of the
      chromosomal pta and ack genes led to the absence of detectable
      phosphotransacetylase and acetate kinase activity in the respective mutants and
      to their inability to grow on acetate. These data indicate that no isoenzymes of
      acetate kinase and phosphotransacetylase are present in Corynebacterium
      glutamicum and that a functional acetate kinase/phosphotransacetylase pathway is
      essential for growth of this organism on acetate.

PMID- 10075433
TI  - Reproductive biology of female titi monkeys (Callicebus moloch) in captivity.
AB  - Titi monkeys (Callicebus spp., Cebidae) are monogamous neotropical primates that
      live in family-like groups typically consisting of an adult monogamous pair and
      one or two young. Knowledge about the reproductive biology of this genus is
      scanty. This study investigated the reproductive biology of female dusky titi
      monkeys (Callicebus moloch). An initial analysis characterized reproductive
      parameters of 32 females from a captive colony maintained for 23 years at the
      California Regional Primate Research Center (CRPRC). The colony records provided
      data on reproductive parameters such as interbirth intervals, seasonality, age at
      first pregnancy, and reproductive rate in captivity. Changes in urinary levels of
      estrone conjugates (E1C) and pregnanediol-3alpha-glucuronide (PdG) were used to
      characterize major reproductive events. Urine samples from eleven females were
      collected during 17 months. The endocrine data were used to examine changes
      associated with cycling, conception, and the post-partum period as well as to
      determine the duration of the ovarian cycle and gestation length. The analysis of
      colony records indicated that females whose infant survived through weaning gave
      birth at intervals remarkably close to one year, while those who lost their
      offspring showed a significantly shorter interval. As long as they lived within
      the family group, mature female offspring did not breed. The analysis of the
      endocrine profiles indicated that after giving birth to a viable offspring,
      females undergo a relatively prolonged period of anovulation (approx. 6.5
      months), followed by 1-3 non-conceptive cycles (approx. 1 month), after which
      they conceive and gestate (4.3 months).

PMID- 10075434
TI  - Mahale chimpanzees: grouping patterns and cycling females.
AB  - The social system of chimpanzees (Pan troglodytes schweinfurthii) is
      characterized by the fission-fusion of social groups. Several studies have
      reported that females are less gregarious than males. In the current study, adult
      female gregariousness depended on their reproductive state. Noncycling adult
      females (pregnant, lactating, or post reproductive) were observed in large
      bisexual parties less often than cycling adult females. On the other hand,
      cycling adult females were observed in large bisexual parties as often as males,
      regardless of their estrous state. More males were in parties that included
      cycling adult females with maximal genital swelling (estrous females) than in
      parties without them. Moreover, a bisexual party including more estrous females
      contained more males. These results suggest that large bisexual parties of
      chimpanzees are constructed by a dual mechanism. First, cycling adult females are
      attracted to parties that consist of the top ranking male and large numbers of
      adult and adolescent males. Second, adult and adolescent males that did not
      belong to parties originally are attracted by estrous females and join them.
      Thus, in Mahale Mountains National Park, Tanzania, bisexual parties of
      chimpanzees can be characterized as "parties for reproduction."

PMID- 10075435
TI  - Effects of separation and novelty on distress vocalizations and cortisol in the
      common marmoset (Callithrix jacchus).
AB  - In socially-bonding species, separation from familiar attachment figures is
      widely known to stimulate a physiological and behavioral stress response. This
      study investigated the hormonal and vocal responses of adult common marmosets to
      separation from familiar group members and to 24 hr of cohabitation with an
      unfamiliar opposite-sex conspecific. All subjects were removed from their home
      cages and placed into a novel environment for 20 min. In one group, marmosets
      were exposed to an unfamiliar, opposite-sex partner in the novel environment and
      remained paired with this partner for the 24 hr test period. In three other
      groups, marmosets experienced the novel environment alone and subsequently were
      returned to their original social- or single-housing condition, or kept separate
      from their social groups for a 24 h period. Blood samples were collected the day
      before, and at 30 min, 90 min, and at 24 h after separation. Cortisol responses
      were differentially affected by the length of separation and the presence of
      unfamiliar conspecifics. Brief separation followed by the return to the social
      group had minimal effect on plasma cortisol levels. All marmosets produced high
      levels of separation calls in the novel environment, but there was no apparent
      relationship between calling and cortisol levels. The lack of a temporal
      relationship between the production of distress vocalizations and serum cortisol
      has previously been noted in squirrel monkey and rhesus monkey infant separation
      studies; the behavioral and physiological responses to separation appear to be
      similarly dissociated in the marmoset. Further, the characteristics of a
      separation environment can differentially affect the hormonal response by adult
      marmosets without differentially affecting their behavioral response.

PMID- 10075436
TI  - Islet cell antibodies in Sulawesi macaques.
AB  - Older monkeys of the Sulawesian species Macaca nigra spontaneously develop a
      lesion in the pancreatic islets of Langerhans in which there is deposition of
      amyloid and gradual degeneration of all cells, which can lead eventually to
      development of diabetes mellitus. Islet cell antibodies (ICA), formed in response
      to the release of cellular antigens, can be used to detect the islet lesion and
      to monitor the progression of each monkey toward diabetes. Numerous M. nigra and
      one M. tonkeana in captivity have been tested, but it is unknown whether the
      islet lesion occurs in monkeys in their natural habitat of Sulawesi. Blood
      samples collected from M. maurus, M. tonkeana, and hybrid M. maurus/tonkeana were
      assayed for ICA. When all monkeys were considered together, 33% had ICA positive
      against beta cells and 14% had ICA positive against alpha and/or D cells.
      Appearance of ICA in blood of males was virtually the same as in females. These
      results are similar to those found in M. nigra examined in captivity. Since all
      Sulawesian species share a common genetic heritage, these results would support
      the appearance of this lesion in their natural habitat. Cause(s) for formation of
      the lesion and eventual development of diabetes are unknown. There may be genetic
      factors or genetic predisposition to environmental factors. If environmental
      factors are responsible, then they must be present not only in the wild, but
      either carried with the monkeys or universally available, since M. nigra born in
      captivity also develop the lesion and diabetes after physical maturity at ca. 7+
      years.

PMID- 10075437
TI  - Diurnal changes in plasma prolactin during the last one third of pregnancy in the
      baboon.
AB  - Previous studies in our laboratory revealed that daily plasma prolactin (Prl)
      levels were higher in the evening than in the morning in the pregnant baboon
      suggesting a diurnal variation. The goal of this study was to examine in more
      detail the diurnal alterations in plasma Prl levels. A tethered pregnant baboon
      model was utilized for these studies. Hourly venous blood samples were taken from
      0700 to 2400 hr (n=10) or until 0700 hr the following day (n=5). The studies were
      performed at various days of pregnancy from day 135 until delivery. Plasma
      samples were analyzed for Prl by radioimmunoassay. A surge in plasma Prl was
      detected, starting around 1500 to 1600 hr and lasting for 3 to 5 hr. The surge
      occurred before the lights went off in the colony (1800 hr). Baseline Prl levels
      were higher in animals < 15 days before delivery compared to those > 15 days
      before delivery (P < 0.05). In contrast, no differences were found in the average
      peak Prl values between these two groups of animals. In summary, in the pregnant
      baboon during the last one-third of pregnancy plasma Prl surges, beginning around
      1500 to 1600 hr and lasting for 3 to 5 hr. Less than 15 days before delivery the
      mean baseline Prl levels are higher compared to animals greater than 15 days
      before delivery.

PMID- 10075438
TI  - The influence of abiotic factors on the onset and cessation of activity of semi
      free Callithrix jacchus.
AB  - The influence of abiotic environmental factors on the period of activity of a
      single group of South American common marmosets (Callithrix jacchus,
      Callitrichidae, Primates) was investigated under semi-free conditions. A group of
      eight members had a territory consisting of a heated wooden hut with a veranda,
      surrounded by an open area with a few trees (ca. 3.5 m high) and three runways
      made out of roofing slats, on which feeding places and sleeping boxes were fixed.
      The food supply was held constant throughout the observation period with respect
      to amount, composition and spatial distribution. From July to November 1995, the
      times of the onset and cessation of activity were determined using a video
      camera. An electronic weather station recorded the temperature, humidity, air
      pressure, wind speed, wind direction, precipitation, and light intensity at
      intervals of 5 min. There was a linear correlation between day light length and
      the length of the period of activity over a day length of 10 to 14 hr. With
      shorter day lengths, the marmosets were also active during the twilight, whereas
      with longer day lengths a sleep phase during the late morning was introduced.
      Ambient temperature and humidity had also an effect on the time when activity
      began or ceased. Callithrix jacchus has one of the longest activity periods
      within the Callitrichidae. The time of sunrise or sunset, temperature, and
      humidity accounted for 66.2% of the variation in the time when activity began and
      75.5% of the variance in the cessation of activity of the study group within the
      multivariate model. The results from the present study add to the indications
      that in the Callitrichidae there is a strong selection pressure for the highest
      possible energy saving during the comparatively long phase of inactivity.

PMID- 10075439
TI  - Ingestion of calcium solutions by common marmosets (Callithrix jacchus).
AB  - Callithrix jacchus, the common marmoset, is a small New World primate that feeds
      on insects, fruit, and gum, and has a high reproductive rate for a primate.
      Insects are generally a poor source of dietary calcium, while gums may contain
      significant levels of calcium. Their high reproductive rate also suggests that
      reproductive female C. jacchus might be susceptible to calcium deficiency. Thus,
      we hypothesized that common marmosets might find solutions containing calcium to
      be palatable. We used choice experiments to examine this phenomenon in 14 male
      and 19 female common marmosets. Animals were presented with identical water
      bottles containing either deionized water or a calcium lactate solution (either
      2% or 4% calcium lactate by weight) and intake was measured. Serum 25-OH-vitamin
      D was monitored in a subset of the animals in the experiment to examine the role
      of vitamin D in this behavior. Our results demonstrated that C. jacchus can
      distinguish between plain water and a calcium lactate solution, and that in
      general they prefer calcium solutions. Although animals with marginal vitamin D
      status did have strong preferences for calcium solutions, they did not ingest
      significantly more of the calcium solutions than animals that were vitamin D
      replete. Nulliparous females and males did not differ in the amounts of calcium
      solutions ingested. Lactating females ingested the greatest volume of the calcium
      solutions.

PMID- 10075441
TI  - Visual abnormalities in albino wallabies: a brief note.
AB  - Abnormally reduced uncrossed retinofugal pathways and abnormally low retinal cell
      densities have been described in albinos of a number of species of eutherian
      mammal, but have not been studied in marsupials. The optic chiasm of marsupials
      differs from that of the eutherian brains that have been studied, with uncrossed
      fibres segregating from crossed fibres prechiasmatically in the marsupials, but
      not in the eutherians. We have examined the optic chiasm and the retina in albino
      and normally pigmented wallabies (Macropus rufogriseus) to determine whether the
      abnormalities found in eutherian albinos are also present in this marsupial. The
      uncrossed pathway of the albino wallaby is smaller than that of the pigmented
      animals and the cell density in the retinal ganglion cell layer is reduced at the
      area centralis. We conclude that the characteristic albino abnormalities are
      present in both groups of mammals in spite of the other known differences in the
      visual pathways. The albino mutation acts at the chiasm in a similar manner in
      both groups even though the determinants of the chiasmatic pathway differ.

PMID- 10075440
TI  - Organization of somatosensory cortex in three species of marsupials, Dasyurus
      hallucatus, Dactylopsila trivirgata, and Monodelphis domestica: neural correlates
      of morphological specializations.
AB  - The organization of somatosensory neocortex was investigated in three species of
      marsupials, the northern quoll (Dasyurus hallucatus), the striped possum
      (Dactylopsila trivirgata), and the short-tailed opossum (Monodelphis domestica).
      In these species, multiunit microelectrode mapping techniques were used to
      determine the detailed organization of the primary somatosensory area (SI). In
      the striped possum and quoll, the topography of somatosensory regions rostral
      (R), and caudal (C) to SI were described as well. Lateral to SI, two fields were
      identified in the striped possum, the second somatosensory area (SII) and the
      parietal ventral area (PV); in the quoll, there appeared to be only one
      additional lateral field which we term SII/PV. Visual and auditory cortices
      adjacent to somatosensory cortex were also explored, but the details of
      organization of these regions were not ascertained. In these animals,
      electrophysiological recording results were related to cortical myeloarchitecture
      and/or cytochrome oxidase staining. In one additional species, the fat-tailed
      dunnart (Sminthopsis crassicaudata), an architectonic analysis alone was carried
      out, and compared with the cortical architecture and electrophysiological
      recording results in the other three species. We discuss our results on the
      internal organization of SI in relation to the morphological specializations that
      each animal possesses. In addition, we discuss the differences in the
      organization of SI, and how evolutionary processes and developmental and adult
      neocortical plasticity may contribute to the observed variations in SI.

PMID- 10075442
TI  - Cellular and subcellular structure of anterior sensory pathways in Phestilla
      sibogae (Gastropoda, Nudibranchia).
AB  - Two sensory-cell types, subepithelial sensory cells (SSCs) and intraepithelial
      sensory cells (ISCs), were identified in the anterior sensory organs (ASO: pairs
      of rhinophores and oral tentacles, and the anterior field formed by the oral
      plate and cephalic shield) of the nudibranch Phestilla sibogae after filling
      through anterior nerves with the neuronal tracers biocytin and Lucifer Yellow. A
      third type of sensory cells, with subepithelial somata and tufts of stiff-cilia
      (TSCs, presumably rheoreceptors), was identified after uptake of the
      mitochondrial dye DASPEI. Each sensory-cell type has a specific spatial
      distribution in the ASO. The highest density of ISCs is in the oral tentacles
      (approximately 1,200/mm2), SSCs in the middle parts of the rhinophores
      (>4,000/mm2), and TSCs in the tips of cephalic tentacles (100/mm2). These
      morphologic data, together with electrophysiologic evidence for greater chemical
      sensitivity of the rhinophores than the oral tentacles (Murphy and Hadfield
      [1997] Comp. Biochem. Physiol. 118A:727-735; Boudko et al. [1997] Soc. Neurosci.
      Abstr. 23:1787), led us to conclude that the two pairs of chemosensory tentacles
      serve different chemosensory functions in P. sibogae; i.e., ISCs and the oral
      tentacles serve contact- or short-distance chemoreception, and SSCs and the
      rhinophores function for long-distance chemoreception or olfaction. If this is
      true, then the ISC subsystem probably represents an earlier stage in the
      evolution and adaptations of gastropod chemosensory biology, whereas among the
      opisthobranchs, the SSC subsystem evolved with the rhinophores from ancestral
      cephalaspidean opisthobranchs.

PMID- 10075443
TI  - Distribution of acetylcholinesterase and choline acetyltransferase in the main
      and accessory olfactory bulbs of the hedgehog (Erinaceus europaeus).
AB  - The distribution of cholinergic markers was studied in the main olfactory bulb
      (MOB) and accessory olfactory bulb (AOB) of the western European hedgehog
      (Erinaceus europaeus) by using choline acetyltransferase (ChAT)
      immunocytochemistry and acetylcholinesterase (AChE) histochemistry. A dense
      network of AChE-containing and ChAT-immunoreactive fibers was observed
      innervating all layers of the MOB except the olfactory nerve layer, where neither
      AChE- nor ChAT-labeled elements were found. The highest density of AChE- and ChAT
      positive axons was found in the glomerular layer (GL)/external plexiform layer
      (EPL) boundary, and in the internal plexiform layer. This general distribution
      pattern of ChAT- and AChE-stained axons resembled the distribution pattern found
      in rodents. Nevertheless, some interspecies differences, such as the lack of
      atypical glomeruli in the hedgehog, were also found. In addition to fibers, a
      population of noncholinergic and presumably cholinoceptive AChE-active neurons
      was observed in the hedgehog. All mitral and tufted cells of the hedgehog MOB
      showed a dark AChE staining unlike previous observations in the mitral and tufted
      cells of rodents. As in other species previously reported, subpopulations of
      external tufted cells and short-axon cells were also AChE-active. Finally, a
      population of small AChE-containing cells was observed in the EPL of the hedgehog
      MOB. The size, shape, and location of these cells coincided with those of
      satellite and perinidal cells, two neuronal types described previously in the EPL
      of the hedgehog and not present in the rodent MOB. The AOB of the hedgehog showed
      a distribution of AChE- and ChAT-positive fibers similar to the rodent AOB.
      Nevertheless, a heterogeneous innervation of vomeronasal glomeruli by bundles of
      AChE- and ChAT-labeled axons found in the hedgehog has not been previously found
      in any other species. As in the MOB, all mitral cells in the AOB showed a strong
      AChE activity. These results demonstrate some similarities but also important
      differences between the distribution of ChAT and AChE in the MOB and AOB of
      rodents and this primitive mammalian. These variations may indicate a different
      organization of the cholinergic modulation of the olfactory information in the
      insectivores.

PMID- 10075444
TI  - Long-range GABAergic projection in a circuit essential for vocal learning.
AB  - The anterior forebrain pathway (AFP) in the passerine song system is essential
      for song learning but not for song production. Several lines of evidence suggest
      that area X, a major nucleus in the AFP, forms part of the avian striatum. A key
      feature of striatal projection neurons is that they use the inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA). Some area X neurons express GABA
      like immunoreactivity, but the neurotransmitter phenotype of the projection
      neurons is largely unknown. To determine whether area X projection neurons are
      GABAergic, we used immunocytochemistry and confocal microscopy to examine whether
      these neurons in adult male zebra finches express the GABA synthetic enzyme
      glutamic acid decarboxylase (GAD). We observed numerous large and small GAD+
      somata in area X, and dense GAD+ terminals, but no GAD+ somata in the target of
      area X, the medial nucleus of the dorsolateral thalamus (DLM). The density of
      GAD+ terminals in DLM was strongly reduced by ibotenic acid lesions of area X.
      After tracer injection into the DLM, all of the retrogradely labeled neurons in
      area X were GAD+. After tracer injection into area X, the vast majority of
      anterogradely labeled terminals in DLM were GAD+. We conclude that area X neurons
      projecting to DLM express GAD and are thus likely GABAergic. If this projection
      is indeed inhibitory, information processing in the AFP is substantially more
      complicated than previously realized. Moreover, because a GABAergic projection to
      a thalamic target is reminiscent of pallidal rather than of striatal circuitry,
      area X may contain both striatal and pallidal components.

PMID- 10075445
TI  - Allatostatin-like immunoreactivity in the stomatogastric nervous system and the
      pericardial organs of the crab Cancer pagurus, the lobster Homarus americanus,
      and the crayfish Cherax destructor and Procambarus clarkii.
AB  - The distribution of allatostatin (AST)-like immunoreactivity was studied in the
      stomatogastric nervous system (STNS) and the neurosecretory pericardial organs
      (PO) of four decapod crustacean species by using wholemount immunocytochemical
      techniques and confocal microscopy. AST-like immunoreactivity was found within
      the STNS of all four species; its distribution in each was unique. In all four
      species, AST-like immunoreactivity was present in the paired commissural ganglia
      (CoG), in the esophageal ganglion (OG), in the stomatogastric ganglion (STG), and
      in their connecting nerves. Within the CoGs, numerous cell bodies and neuropil
      were stained. In the OG, two cell bodies were immunoreactive, although their
      branching pattern varies between species. In the STG of C. pagurus and H.
      americanus, neuropil was stained extensively, but no labeled cell bodies were
      found. Surprisingly, in C. destructor and P. clarkii, cell bodies were stained in
      the STG, one brightly stained cell body in both species and an additional two to
      five weakly stained cell bodies in P. clarkii. In all four species, stained
      gastropyloric receptor cells were present. In contrast to the variable staining
      within the STNS, all four species have a similar pattern of AST-like
      immunoreactivity within the PO. Only in C. destructor, AST-immunoreactive
      varicosities occur on the surface of the circumesophageal connectives and on the
      postesophageal commissure and suggest another neurohaemal source for AST-like
      peptides in this species. The pattern of this staining suggests that AST-like
      peptides are likely utilized as both neurohormones and as neuromodulators in the
      STNS of decapod crustacea.

PMID- 10075446
TI  - Clonal mixing, clonal restriction, and specification of cell types in the
      developing rat olfactory bulb.
AB  - To understand the clonal relationship of various olfactory bulb (OB) cell types,
      OB progenitor cells were infected at embryonic day (E) 14, E15, and E17 with
      retroviral libraries encoding alkaline phosphatase or beta-galactosidase. After
      survival to postnatal day 10-15, sibling relationships were identified by
      polymerase chain reaction DNA amplification of distinct sequences in the
      retroviral constructs. Within the OB, clonal progeny dispersed widely in all
      directions. In sharp contrast, however, clonal dispersion between the OB and
      neocortex was not observed, although occasional clonal dispersion between the OB
      and pyriform and hippocampal regions could not be excluded. Most clones (84%)
      contained a single cell type, especially after E17 injections, suggesting the
      existence of either restricted precursors, or multipotential progenitors
      instructed by a restricted cellular environment. Mixed OB clones (16%) contained
      multiple cell types in the OB, or occasionally glial or neuronal cells outside
      the OB, demonstrating the existence of multipotential OB progenitors, likely at a
      stage before formation of the olfactory rostral migratory stream. Surprisingly,
      OB glial cells were not labeled, suggesting distinct lineages or perhaps distinct
      migratory paths for glia and neurons into the OB. A hierarchical cell lineage is
      proposed that involves a multipotential progenitor that gives rise to potentially
      more limited progenitors.

PMID- 10075447
TI  - Distribution and activation of different types of octopaminergic DUM neurons in
      the locust.
AB  - The first part of this study describes the distribution of all different types of
      octopaminergic, efferent dorsal unpaired median (DUM) neurons in the first two
      thoracic ganglia by immunocytochemistry, retrograde labeling, and intracellular
      staining. The prothoracic ganglion contains five different types of 10 DUM
      neurons. The mesothoracic ganglion has 21 octopaminergic somata in the DUM neuron
      cluster. Retrograde labeling and intracellular staining show that 19 of these 21
      somata belong to five different types of efferent DUM neurons. In both ganglia,
      the number and the distribution of all types of DUM neurons are completely
      described. Differences in the distribution of efferent DUM neurons between the
      thoracic ganglia are discussed as functional segmental specializations. In the
      second part, we show that, in contrast to previous suggestions, DUM neurons are
      not recruited as a homogeneous population mediating general arousal but
      differentially, thus forming subpopulations of specific types. The existence or
      the absence of commonly occurring postsynaptic potentials in paired recordings
      clearly shows that only specific types of DUM neurons are targeted by the same
      presynaptic pathways. Within the thoracic ganglia, different subpopulations of
      DUM neurons can be distinguished by their different local inputs. Furthermore,
      only specific subpopulations of DUM neurons receive common intersegmental drive
      and inputs from the subesophageal ganglion. As a result of all our recordings, we
      propose a scheme for the differential activation of efferent DUM neurons. This
      scheme is sufficient to explain DUM neuron activity during principal motor
      programs.

PMID- 10075449
TI  - The European consensus development conference on neonatal hearing screening
      (Milan, 15-16 May, 1998).

PMID- 10075448
TI  - Low false-positive rate of aneuploidy detection using fetal cells isolated from
      maternal blood.

PMID- 10075450
TI  - Proceedings of the 1st Coimbra International Meeting on Cardiovascular Diseases:
      Acute Myocardial Infarction. Coimbra, Portugal, 3-4 October 1997.

PMID- 10075451
TI  - Postgraduate orthodontic training programmes in the UK, 1998.

PMID- 10075452
TI  - Orthodontic products update. Cross infection control and elastomeric module
      delivery systems.

PMID- 10075453
TI  - Function and Clinical Perspectives of Angiotensin II Subtype 1 (AT1) Receptors.
      Workshop proceedings. Budapest, Hungary, May 6-9, 1998.

PMID- 10075454
TI  - Regulated binding of the Fanconi anemia proteins, FANCA and FANCC.

PMID- 10075455
TI  - Factor V Leiden is not a risk factor for myocardial infarction among young women.

PMID- 10075456
TI  - GATA-1 transcription factor transactivates the promoter for CCR5, a coreceptor
      for human immunodeficiency virus type 1 entry.

PMID- 10075457
TI  - Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid
      leukemia cells.

PMID- 10075458
TI  - Interleukin-8 in acute myeloid leukemia.

PMID- 10075459
TI  - Association of CD10/neutral endopeptidase 24.11 with membrane microdomains rich
      in glycosylphosphatidylinositol-anchored proteins and Lyn kinase.

PMID- 10075460
TI  - Commentary: Progress on nicotine replacement therapy for smokers.

PMID- 10075461
TI  - Commentary: counting heads may mask cultural and social factors.

PMID- 10075462
TI  - Deprivation and emergency admissions for cancers. Social factors affect patterns
      of referral for breast cancer.

PMID- 10075463
TI  - Effect of flutamide on survival in patients with pancreatic cancer. Results are
      impressive.

PMID- 10075464
TI  - Effect of flutamide on survival in patients with pancreatic cancer. No
      recommendations can be made.

PMID- 10075465
TI  - Intravenous beta blockade in acute myocardial infarction. Case for intravenous
      beta blockade for patients given thrombolysis is still uncertain.

PMID- 10075466
TI  - Intravenous beta blockade in acute myocardial infarction. In one health district,
      only 0.2% eligible for intravenous blockade received it.

PMID- 10075467
TI  - Standards in advertising. Editorial control over controversial contents?

PMID- 10075468
TI  - Implementing research findings in developing countries. Medical curriculums need
      changing.

PMID- 10075469
TI  - Commentary: trials versus models in appraising screening programmes.

PMID- 10075470
TI  - JAMA's editor sacked. Dark cloud of sanctimonious clinche settles on BMJ's
      website.

PMID- 10075471
TI  - JAMA's editor sacked. World medical journal editors should draw up email protest
      petition.

PMID- 10075472
TI  - NHS breast screening programme. Growth rate is more important than size.

PMID- 10075473
TI  - NHS breast screening programme. Money may be better spent on symptomatic women.

PMID- 10075474
TI  - NHS breast screening programme. Modelling is suspect, and results lack confidence
      intervals.

PMID- 10075475
TI  - Reply to the letter: about systemic lupus erythematosus and thrombotic
      thrombocytopenic purpura.

PMID- 10075476
TI  - VII International Symposium on Blood Substitutes. Tokyo, Japan, 7-10 September
      1997. Abstracts.

PMID- 10075477
TI  - Total sputum nitrate plus nitrite is raised during acute pulmonary infection in
      cystic fibrosis.

PMID- 10075478
TI  - Nutrition and therapeutics.

PMID- 10075479
TI  - Genetics and molecular biology.

PMID- 10075480
TI  - Lipid metabolism.

PMID- 10075481
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 10075482
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 10075483
TI  - Therapy and clinical trials.

PMID- 10075484
TI  - Tauropine dehydrogenase from the starfish Asterina pectinifera (Echinodermata:
      Asteroidea): presence of opine production pathway in a deuterostome invertebrate.
AB  - Tauropine dehydrogenase (tauropine:NAD oxidoreductase; TaDH) was purified to
      homogeneity from the body wall of the starfish Asterina pectinifera Muller at
      Troschel(Echinodermata: Asteroidea) by means of (NH4)2SO4 precipitation followed
      by column chromatographies in DEAE-cellulose, Sephadex G75, Macro-prep ceramic
      hydroxyapatite, PBE 94, and Toyopearl HW50S. The enzyme was a monomeric protein
      of approximately 42000 Da and pI 5.2. The maximum rate of the tauropine
      biosynthetic reaction was observed at pH 6.0, and that of the tauropine catabolic
      reaction was at pH 8.7-9.2. Taurine and pyruvate were the preferred substrates.
      The tauropine catabolic reaction was inhibited by the substrate tauropine: the
      peak rate was observed at 12.5 mM. Apparent Km values for NADH, taurine, and
      pyruvate were 0.036 +/- 0.002, 21.3 +/- 1.6, and 0.46 +/- 0.02 mM, respectively,
      and for tauropine and NAD+ were 2.64 +/- 0.73 and 0.068 +/- 0.005 mM,
      respectively. The molecular and catalytic properties of the starfish TaDH were
      basically similar to those of TaDH from other species belonging to the lower
      invertebrate phyla and the middle phyla of Prostostomia. Tauropine accumulation
      in vivo during experimental anoxia was also demonstrated. These results gave
      clear evidence of opine production pathway in deutrostome invertebrate.

PMID- 10075485
TI  - [A rare case of embolism of the brachial artery].

PMID- 10075486
TI  - International scanning section: CPR.

PMID- 10075487
TI  - [Solitude in the elderly].
AB  - Elderly people who are deprived of the warmth of human contact are at the risk of
      turning inward. For the very old, an atmosphere such as this can become
      psychologically catastrophic and lead to depressive syndromes such as extreme
      sadness, a desire to do nothing, sleep problems and even dementia. An in-depth
      analysis of the environment of the elderly inspires readers to address care
      objectives and interventions that will minimize and prevent these negative
      consequences.

PMID- 10075488
TI  - Notch signalling in Drosophila: three ways to use a pathway.
AB  - Cell-cell interactions mediated by Notch are critical at multiple stages of
      development. Our current understanding of the Notch signalling pathway suggests a
      comparatively simple transduction mechanism. However, this core pathway can be
      deployed in three different types of developmental process: lateral inhibition,
      lineage decisions and boundary formation. These illustrate how the activity of
      the pathway can be modulated both at the cell surface, through availability and
      effectiveness of ligand interactions, and inside the cell, through effects on the
      transduction pathway and the responsiveness of target genes.

PMID- 10075489
TI  - Notch signalling pathway and human diseases.
AB  - Several homologs of the Drosophila Notch receptor and its ligands, Delta/Serrate,
      have been cloned in man. Three human disorders including a neoplasia (a T-cell
      acute lymphoblastic leukemia/lymphoma), a late onset neurological disease
      (CADASIL) and a developmental disorder (the Alagille syndrome) are associated
      with mutations in, respectively, the Notch1, Notch3 and Jagged1 genes, pointing
      out the broad spectrum of Notch activity in humans. We report herein on what has
      been learned on the role of these human Notch genes and the mechanisms leading
      from mutations in those genes to the observed phenotypes.

PMID- 10075490
TI  - From the Clinical Effectiveness Committee. Use of rifampicin and contraceptive
      steroids.

PMID- 10075491
TI  - Calculating induced abortion rates--a reply.

PMID- 10075492
TI  - Endogenous endophthalmitis by Fusarium solani: an animal experimental model.
AB  - An experimental model of endophthalmitis by Fusarium solani in immunocompetent
      mice that could be useful for evaluating the efficacy of different treatments and
      the pathogenicity of the fungus in ocular structures was established. Five
      clinical isolates of F. solani were injected into the lateral tail vein of groups
      of 20 mice, in order to produce systemic infection with ocular infection. Inocula
      of 5 x 10(6) conidia per mouse were used. The eyes of the animals that died were
      enucleated for histopathological study to determine the degree of ocular
      infection. We found fungal infections in 34% of the mice studied. Panophthalmitis
      was detected in 16 animals, four with bilateral infections. Fungal
      endophthalmitis can become a severe complication of systemic mycoses by F.
      solani.

PMID- 10075493
TI  - Isozyme variation of Microsporum canis and M. cookei from New Zealand.
AB  - Fifty-four isolates of Microsporum canis (Arthroderma otae) from humans, cats and
      dogs obtained from Auckland, Palmerston North and Wellington, New Zealand and 18
      M. cookei and two Diheterospori spp. from soils were examined for variation using
      eight isozyme loci. M. canis isolates were from infected and non-infected cases.
      Isozyme analysis separated the three species which were further subdivided into
      electrophoretic types (ETs). Clustering analysis using normalized percentage
      disagreement (PTC) average linkage method revealed two clusters for M. cookei
      with two subclusters in cluster 2. M. canis had three main divisions (clusters 3,
      4 and 5) and Diheterospora formed a separate division. The presence of isolates
      from different sources in the same clusters and lack of statistical significance
      as measured by confidence intervals suggests the existence of isolates with
      common lineage.

PMID- 10075494
TI  - Isolation of fungal rDNA from bottlenose dolphin skin infected with Loboa loboi.
AB  - Fungal-specific primers targeted for highly conserved genomic nucleic acid
      sequences were used in a polymerase chain reaction (PCR) to amplify DNA from
      lobomycosis lesions in a bottlenose dolphin. Sequence alignments of this DNA
      possessed high homology to fungal ribosomal DNA sequences found in the genus
      Cladosporium. When used for in situ hybridization, the riboprobe transcribed from
      a cloned PCR-generated fragment bound to Loboa loboi cells. These results support
      the hypothesis that L. loboi in dolphin tissue is a fungus.

PMID- 10075495
TI  - Serum interferon-gamma (IFN-gamma) in chronic oral candidosis.
AB  - Serum IFN-gamma levels were studied in adult patients with chronic oral
      candidosis, associated with Candida albicans infection. In the group of patients,
      mean serum IFN-gamma levels (2.74+/-465 pg ml(-1)) were significantly lower than
      in healthy individuals (9.80+/-1.68 pg ml(-1)). In analysis of the C. albicans
      strains isolated from lesions in the patients, their ability was estimated to
      secrete proteinases. Serum IFN-gamma levels failed to correlate with infections
      induced by proteinase-producing C. albicans. The results allowed us to conclude
      that Candida infection may be associated with an insufficient IFN-gamma response
      of the host, which seems to result in chronic conversion of candidosis.
      Proteolytic activity of C. albicans strains in vitro is not related to virulence
      of the strains.

PMID- 10075496
TI  - Detection of PCR-amplified fungal DNA by using a PCR-ELISA system.
AB  - In order to speed up and standardize polymerase chain reaction (PCR)-based
      detection of medically important fungi in clinical samples we established a
      combination of commercially available kits for DNA extraction, PCR amplification
      and detection of the amplicons. The PCR plate assay proved to be as sensitive and
      specific as our previously published assay (5 cfu ml(-1) blood). Moreover, in a
      selected group of patients, all patients with proven and probable invasive fungal
      infection were found to be PCR-positive. Thus the PCR plate assay was found to be
      a sensitive, technically simplified and standardized method with potential for
      adaptation to automation.

PMID- 10075497
TI  - Activated lymphocytes reduce adherence of Aspergillus fumigatus.
AB  - Lymphocytes comprise up to 30% of the cells present in human bronchoalveolar
      lavage fluid and thus could participate in host response to infectious
      Aspergillus fumigatus conidia. We have examined the possibility that lymphocytes
      might play a role during early infection by either damaging the fungus or
      interfering with adherence. When incubated with A. fumigatus conidia for 20 h,
      highly purified 5-day-old lymphocytes activated with either IL-2 or
      phytohaemagglutinin, but not untreated lymphocytes, were consistently able to
      reduce residual fungal biomass as estimated by a metabolic assay. T lymphocytes,
      but not NK cells, appeared to be responsible for this activity. Lymphocytes bound
      both A. fumigatus conidia and hyphae, and the antifungal activity of the
      lymphocytes required direct lymphocyte fungus contact. In a separate set of
      experiments using release of 51Cr from 51Cr-loaded fungi as an estimate of fungal
      damage, lymphocyte-induced loss of fungal biomass was found to be due to loss of
      fungal adherence rather than to direct fungal damage. The detached hyphae were
      also found to be metabolically intact and to have normal morphology by electron
      microscopy. These data demonstrate that IL-2- and phytohaemagglutinin-activated
      lymphocytes exhibit a contact-dependent ability to reduce adherence of
      germinating conidia of A. fumigatus to a surface.

PMID- 10075498
TI  - Fungicidal and binding properties of the natural peptides cecropin B and
      dermaseptin.
AB  - In vitro fungicidal properties of cecropin B and dermaseptin were explored using
      non-germinating and germinating conidia from Aspergillus flavus, A. fumigatus, A.
      niger, Fusarium n2oniliforme and F oxysporum. Cecropin B produced LD50 values for
      germinating A. flavus, A. fumigatus and A. niger conidia of 30, 0.5 and 2.0
      microM, respectively, while dermaseptin gave LD50 values of 4.0, 0.05 and 2.0
      microM, respectively. Cecropin B produced an LD50 value of 0.2 microM for non
      germinating F. moniliforme and F. oxysporum conidia, while dermaseptin did not
      reduce either as much as 50% at any level tested. LD50 levels for CB were 0.2 and
      0.1 microM, respectively, for germinating F. moniliforme and F. oxysporum
      conidia. Dermaseptin was less effective, giving LD50 values for germinating F.
      moniliforme and F. oxysporum conidia of 0.3 and 0.8 microM, respectively. Neither
      peptide reduced conidial viabilities of non-germinating Aspergillus spp.
      Physicochemical studies indicated cecropin B and dermaseptin bound to ergosterol
      and cholesterol, conidial wall constituents, but not to chitin or beta-1,3
      glucan.

PMID- 10075499
TI  - Comparison of six extraction techniques for isolation of DNA from filamentous
      fungi.
AB  - Filamentous fungi have a sturdy cell wall which is resistant to the usual DNA
      extraction procedures. We determined the DNA extraction procedure with the
      greatest yield of high quality fungal DNA and the least predilection for cross
      contamination of equipment between specimens. Each of six extraction methods was
      performed using Aspergillus fumigatus hyphae. The six methods were: (1) glass
      bead pulverization with vortexing; (2) grinding with mortar and pestle followed
      by glass bead pulverization; (3) glass bead pulverization using 1% hydroxyacetyl
      trimethyl ammonium bromide (CTAB) buffer in a water bath sonicator; (4) water
      bath sonication in CTAB buffer; (5) grinding followed by incubation with CTAB;
      and (6) lyticase enzymatic cell lysis. Genomic DNA yields were measured by
      spectrophotometry and by visual reading of 2% agarose gels, with shearing
      assessed by the migration of the DNA on the gel. Genomic fungal DNA yields were
      highest for Method 1, followed by Methods 5 approximately = to 2 >3 approximately
      = to 4 approximately = to 6. Methods 2 and 5, both of which involved grinding
      with mortar and pestle, led to shearing of the genomic DNA in one of two trials
      each. We conclude that the use of glass beads with extended vortexing is optimal
      for extraction of microgramme amounts of DNA from filamentous fungal cultures.

PMID- 10075500
TI  - Cryptococcus neoformans isolated from human dwellings in Rio de Janeiro, Brazil:
      an analysis of the domestic environment of AIDS patients with and without
      cryptococcosis.
AB  - One hundred and fifty-four human dwellings in the metropolitan area of Rio de
      Janeiro, Brazil were studied. A total of 824 samples of indoor dust, outdoor soil
      and avian droppings were collected. Cryptococcus neoformans var. neoformans was
      isolated from 20 (13%) dwellings, comprising five (15.6%) of 32 dwellings of
      patients with AIDS-associated cryptococcosis; four (8.9%) of 45 dwellings of
      patients with AIDS but without cryptococcosis; and 11 (14.3%) of 77 dwellings of
      apparently healthy individuals (P>0.05). The principal factor associated with
      domiciliar contamination by C. neoformans var. neoformans was the presence of
      avians in the domestic environment or nearby the home. Cryptococcosis was more
      frequent among AIDS patients residing in dwellings from which C. neoformans var.
      neoformans was isolated than among AIDS patients from whose domestic environment
      the fungus was not demonstrated by the methods used (odds ratio (OR)=2.05). These
      findings suggest that the distribution of C. neoformans var. neoformans in Rio de
      Janeiro is not restricted to the classically known biotopes as well as reinforce
      the possibility of exogenous infection in opportunistic cryptococcosis, including
      exogenous infection acquired in the domestic environment.

PMID- 10075501
TI  - Analysis of peptidogalactomannans from the mycelial surface of Aspergillus
      fumigatus.
AB  - Peptidogalactomannans (pGMs) from mycelium of two strains of Aspergillus
      fumigatus were fractionated by Cetavlon precipitation and size exclusion
      chromatography and their carbohydrate structures analysed using methylation
      fragmentation analysis, partial acetolysis and 13C-nuclear magnetic resonance
      spectroscopy. The most significant difference between the pGMs of the two strains
      was the degree of branching and the proportion of non-reducing ends of alpha-D
      Manp and beta-D-Galf units. Methylation data showed that the pGM from AF 2109
      contained alpha-D-Manp and beta-D-Galf non-reducing end units in a proportion of
      3:1 while, in contrast, the proportion of these structures in pGM from AF 2140
      was 7:1, resulting in a highly branched structure. The immunoreactivity of the
      pGM fractions was tested by indirect immunofluorescence. The fractions were also
      tested in an ELISA system with rabbit antiserum raised to whole cells of A.
      fumigatus NCPF 2140 and with serum from patients with either proven aspergilloma
      or ABPA. The carbohydrate moiety of the pGM appears to be responsible for the
      antigenicity. Periodate treatment, partial acid hydrolysis and beta-elimination
      removed most of the antibody binding capacity.

PMID- 10075502
TI  - A dual labelling method for measuring uptake of low molecular weight compounds
      into the pathogenic yeast Candida albicans.
AB  - In contrast to other eukaryotic cells the pathogenic yeast Candida albicans is
      resistant to many structurally unrelated metabolic inhibitors. Reduced
      permeability due to the cell wall and/or altered plasma membrane composition is
      thought to be at least partly responsible for this phenomenon. To study the
      uptake of low molecular weight compounds into C. albicans we developed a dual
      labelling method. Intact cells, metabolically inactivated cells, spheroplasts or
      membrane fragments of C. albicans were incubated with various [14C]-labelled
      compound in the presence of [3H]-labelled water. After separation of cells and
      supernatant isotope ratios [3H]/[14C] were determined. Quotients of the isotope
      ratios from cells and supernatant, called enrichment coefficients, were
      calculated under all four conditions. The enrichment coefficients indicated
      whether a compound can enter C. albicans cells, is trapped within the cell wall,
      is enriched in the lipophilic membrane compartment, is actively accumulated or
      actively exported by multidrug resistance carriers. We used six structurally
      unrelated compounds to test our method. We found no evidence for a general
      impermeability of C. albicans.

PMID- 10075503
TI  - Pityriasis versicolor with a unique clinical appearance.
AB  - We experienced an atypical case of pityriasis versicolor with a unique clinical
      appearance and undescribed mycological features. Although Malassezia sp. was
      cultured from the keratotic material, the fungal elements observed in the
      material were not readily identified as Malassezia. The diagnosis was established
      with the aid of immunohistochemical and ultrastructural studies with the
      aetiological agent being identified as M. globosa.

PMID- 10075504
TI  - First report of Cryptococcus laurentii meningitis and a fatal case of
      Cryptococcus albidus cryptococcaemia in AIDS patients.
AB  - We report the first case of Cryptococcus laurentii meningitis and a rare case of
      Cryptococcus albidus cryptococcaemia in AIDS patients. Both infections were
      treated with amphotericin B and flucytosine. The C. laurentii meningitis was
      controlled after 2 weeks of treatment with no evidence of infection 20 months
      later. The patient with C. albidus cryptococcaemia, despite the amphotericin
      B/flucytosine combination therapy, died on the 14th day of treatment. The minimum
      inhibitory concentrations (MICs) for C. laurentii, as determined by Etest on RPMI
      1640 agar, were 0.25 microg ml(-1) of amphotericin B, 1.25 microg ml(-1)
      flucytosine, 4 microg ml(-1) fluconazole, 0.50 microg ml(-1) itraconazole and 1.0
      microg ml(-1) of ketoconazole. The MIC of amphotericin B for C. albidus was 0.5
      microg ml(-1), flucytosine 1.25 microg ml(-1), fluzonazole 4 microg ml(-1),
      itraconazole 0.5 microg ml(-1) and ketonazole 0.25 microg ml(-1). The agreement
      of the amphotericin B MIC values obtained in antibiotic medium 3 by the broth
      microdilution method, with those obtained on casitone medium by Etest, was within
      a two-dilution range for both isolates. C. laurentii may cause meningitis and may
      also involve the lungs in AIDS patients.

PMID- 10075505
TI  - First isolation of Cryptococcus neoformans var. gattii, serotype C, from the
      environment in Colombia.
AB  - The natural habitat of Cryptococcus neoformans var. gattii, serotype B in the
      environment was established by Australian investigators who demonstrated its
      association with species of Eucalyptus. The aim of the present study was to
      search for the habitat of this variety in a city of Colombia, where clinical
      cases due to this variety occur with great frequency. For a period of 5 months
      detritus, vegetable material and air samples in and around 68 almond trees
      (Terminalia catappa) located in the city were studied. C. neoformans var. gattii
      serotype C was the only variety isolated from two of the 68 trees sampled. These
      trees were positive for 4 of the 5 months during which they were studied. From
      the first positive sample kept under refrigeration, it was possible to isolate
      the fungus up to 3 months later. This is the first report of the isolation of
      serotype C from the environment. More studies are required in order to establish
      the ecological significance of this finding.

PMID- 10075506
TI  - Exocellular proteolytic activity of Paracoccidioides brasiliensis: cleavage of
      components associated with the basement membrane.
AB  - We have previously characterized an exocellular serine-thiol proteinase activity
      in Paracoccidioides brasiliensis, using as substrates peptides analogous of the
      internally quenched fluorogenic peptide Abz-MKRLTL-EDDnp. In this communication,
      detection of maximal proteinase activity in the culture supernatant fluids
      followed the abrupt increase in the medium pH, owing to the accumulation of
      ammonia generated by urease activity. Culture supernatant fluids collected at the
      peak of proteinase activity against Abz-MRKLTL-EDDnp were able to cleave
      components of the basal membrane of the extracellular matrix (EM), including
      laminin, fibronectin, collagen type IV and proteoglycans, and the proteolytic
      activity was selectively inhibited both by PMSF and p-HMB (sodium 7
      hydroxymercuribenzoate), which are also specific inhibitors of the serine-thiol
      proteinase. Human collagen I, bovine fibrinogen, human immunoglobulin G, BSA or
      P. brasiliensis gp43 were resistant to proteolysis. The kinetics of appearance of
      the proteinase activity against EM substrates coincided with that of proteolysis
      of Abz-MKRLTL-EDDnp. Moreover, chromatographic fractions of culture supernatants
      containing the serine-thiol proteinase at high specific activity were also active
      against EM substrates. These data suggest the involvement of this enzyme activity
      in the degradation of the basement membrane, which is the first step for fungal
      tissue invasion.

PMID- 10075507
TI  - Comments on recent human infections caused by ascomycetes.

PMID- 10075508
TI  - [The breath test with labeled urea for the diagnosis of Helicobacter pylori
      infection].

PMID- 10075509
TI  - Retaining the equilibrium point hypothesis as an abstract description of the
      neuromuscular system.
AB  - The lambda version of the equilibrium point (EP) hypothesis for motor control is
      examined in light of recent criticisms of its various instantiations. Four
      important assumptions that have formed the basis for recent criticism are
      analyzed: First, the assumption that intact muscles possess invariant force
      length characteristics (ICs). Second, that these ICs are of the same form in
      agonist-antagonist pairs. Third, that muscle control is monoparametric and that
      the control parameter, lambda, can be given a neurophysiological interpretation.
      Fourth, that reflex loop time delays and the known, asymmetric, nonlinear
      mechanical properties of muscles can be ignored. Mechanical and
      neurophysiological investigations of the neuromuscular system suggests that none
      of these assumptions is likely to be correct. This has been taken to mean that
      the EP hypothesis is oversimplified and a new approach is needed. It is argued
      that such an approach can be provided without rejecting the EP hypothesis, rather
      to regard it as an input-output description of muscle and associated segmental
      circuits. The operation of the segmental circuitry can be interpreted as having
      the function, at least in part, of compensating for a variety of nonlinearities
      and asymmetries such that the overall system implements the lambda-EP model
      equations.

PMID- 10075510
TI  - Proceedings of a workshop on potency and dosage of von Willebrand factor
      concentrates. Bethesda, Maryland, USA. 26 September 1997.

PMID- 10075511
TI  - The conflict-prone nature of occupational health research and practice.

PMID- 10075512
TI  - Proceedings of the 5th International Symposium on Type 2 Diabetes Mellitus:
      Breaking the Barriers for Improved GLycaemic Control. Copenhagen, Denmark, 7-8
      December 1998.

PMID- 10075513
TI  - Pathogenesis of acute renal failure: new aspects.

PMID- 10075514
TI  - Proceedings of the 4th International Workshop on Chromosome Segregation and
      Aneuploidy. Porto, Portugal, July 1998.

PMID- 10075515
TI  - Phylogenetic analysis of Chlamydia trachomatis.

PMID- 10075516
TI  - Vitamin A and carotenoid research in the Netherlands. Proceedings of a
      conference. Mijdrecht, the Netherlands, 23-24 April 1998.

PMID- 10075517
TI  - Executive summary of cloning human beings: report and recommendations of the
      National Bioethics Advisory Commission.

PMID- 10075518
TI  - Summary of the practice parameters for the assessment and treatment of children
      and adolescents with depressive disorders. American Academy of Child and
      Adolescent Psychiatry.
AB  - This summary provides an overview of the assessment and treatment recommendations
      contained in the Practice Parameters for the Assessment and Treatment of Children
      and Adolescents with Depressive Disorders. Depressive disorders in children and
      adolescents are marked by core symptoms similar to those seen in adults, although
      symptom expression varies greatly with developmental stage. These disorders are
      common, chronic, and recurrent, and they are associated with comorbid psychiatric
      conditions and poor outcome that can be alleviated by early identification and
      treatment. Opinions differ regarding treatment planning and duration of treatment
      required. Development of a treatment relationship with the patient and family is
      crucial for a successful outcome. Psychotherapy is an appropriate treatment for
      all children and adolescents with depressive disorders. Antidepressants may prove
      useful in some cases and are especially recommended for patients with psychosis,
      bipolar depression, and severe depression. Continuation treatment is necessary in
      all patients after the acute phase; long-term maintenance is required in some.
      Early detection and intervention is effective in ameliorating the poor
      psychosocial outcome.

PMID- 10075519
TI  - Position statement. Environmental allergen avoidance in allergic asthma. Ad Hoc
      Working Group on Environmental Allergens and Asthma.

PMID- 10075520
TI  - In vivo model for the experimental manipulation of calcified tissues: a surgical
      approach for accessing the odontogenic organ and associated tissues of the rat
      incisor.
AB  - The tooth organ is extensively used in developmental biology to investigate
      organogenesis and cell differentiation. It also represents an advantageous system
      for the study of the various cellular and extracellular matrix events that
      regulate the formation of both collagenous and noncollagenous calcified tissues.
      This article describes an in vivo surgical approach to access and experimentally
      manipulate the tooth organ and supporting tissues of the rat incisor. By use of a
      dental drill, a "window" was created through the alveolar bone on the buccal
      aspect of the hemimandible at the apical end of the incisor. It is at this site
      that epithelial and mesenchymal precursors are situated and undergo cellular
      differentiation to give rise to cells of the odontogenic organ. Active bone
      remodeling is also observed in this area to accommodate posterior growth of the
      tooth. An osmotic minipump connected to the bony window through an outlet
      catheter was used for controlled and continuous administration of experimental
      agents over a predetermined period of time. To validate the model, vinblastine
      sulfate, fetuingold, and dinitrophenylated albumin were thus infused. The animals
      were then sacrificed and the hemimandibles were processed for histological and
      immunocytochemical analyses. The effects of the drug and the presence of tracers
      were restricted to the treated hemimandible and were found in the enamel organ
      and pulp, as well as in the tooth supporting tissues. Cellular changes typically
      associated with the administration of vinblastine were obtained, and tracers were
      localized both in the extracellular milieu and within the endosomal/lysosomal
      elements of cells. These results suggest that this new surgical approach could
      serve as an advantageous in vivo model in which various chemical agents,
      therapeutic drugs, molecular probes are locally administered to study the
      molecular events that regulate calcified tissue formation.

PMID- 10075521
TI  - Viral haemorrhagic fever guidelines.

PMID- 10075523
TI  - Alzheimer's Disease: From Basic Research to Clinical Applications. Proceedings of
      an international conference. Leipzig, June 5-7, 1997.

PMID- 10075522
TI  - Representational momentum for rotations in depth: effects of shadings and axis.
AB  - Representational momentum is a positive memory distortion for an object's final
      position following the presentation of an implied event (J.J. Freyd, 1987).
      Positive memory distortions occur when observers accept test positions beyond the
      final presented position, or forward along the implied trajectory, as the same
      more readily than positions behind the final position. Four experiments explored
      implied events depicting rotations about various depth axes in shaded and
      silhouette conditions. Positive memory distortions were observed for all depth
      rotations under certain shading conditions, with some differences in the size of
      the distortion between axes. No directional effects (e.g., right vs. left) were
      observed. The overall positive memory distortions observed for depth rotations
      contrasted with the negative distortions previously observed for translation
      motion in depth (T.L. Hubbard, 1995 ).

PMID- 10075524
TI  - Structural basis of substrate specificity in malate dehydrogenases: crystal
      structure of a ternary complex of porcine cytoplasmic malate dehydrogenase, alpha
      ketomalonate and tetrahydoNAD.
AB  - The structural basis for the extreme discrimination achieved by malate
      dehydrogenases between a variety of closely related substrates encountered within
      the cell has been difficult to assess because of the lack of an appropriate
      catalytically competent structure of the enzyme. Here, we have determined the
      crystal structure of a ternary complex of porcine cytoplasmic malate
      dehydrogenase with the alternative substrate alpha-ketomalonate and the coenzyme
      analogue 1,4,5,6-tetrahydronicotinamide. Both subunits of the dimeric porcine
      heart, and from the prokaryotes Escherichia coli and Thermus flavus. However,
      large changes are noted around the active site, where a mobile loop now closes to
      bring key residues into contact with the substrate. This observation
      substantiates a postulated mechanism in which the enzyme achieves high levels of
      substrate discrimination through charge balancing in the active site. As the
      activated cofactor/substrate complex has a net negative charge, a positive
      counter-charge is provided by a conserved arginine in the active site loop. The
      enzyme must, however, also discriminate against smaller substrates, such as
      pyruvate. The structure shows in the closed (loop down) catalytically competent
      complex two arginine residues (91 and 97) are driven into close proximity.
      Without the complimentary, negative charge of the substrate side-chain of
      oxaloacetate or alpha-ketomalonate, charge repulsion would resist formation
      production of this catalytically productive conformation, hence minimising the
      effectiveness of pyruvate as a substrate. By this mechanism, malate dehydrogenase
      uses charge balancing to achieve fivefold orders of magnitude in discrimination
      between potential substrates.

PMID- 10075525
TI  - Advances in Neurobehavioral Pharmacology (IV): Opioids, Antinociception and
      Stress. Proceedings of the 7th annual meeting of the Japanese Young Researchers'
      Society of Neurobehavioral Pharmacology. Osaka, Japan, March 22, 1998.

PMID- 10075526
TI  - Loss of rural practitioners.

PMID- 10075527
TI  - Hematopoietic stem-cell transplantation for acute leukemia.

PMID- 10075528
TI  - Hematopoietic stem-cell transplantation for acute leukemia.

PMID- 10075529
TI  - Hematopoietic stem-cell transplantation for acute leukemia.

PMID- 10075530
TI  - Hematopoietic stem-cell transplantation for acute leukemia.

PMID- 10075531
TI  - Hormonal treatment of prostate cancer.

PMID- 10075532
TI  - Cardiovascular risk factors and Medicare costs.

PMID- 10075533
TI  - Cardiovascular risk factors and Medicare costs.

PMID- 10075534
TI  - Interstitial nephritis in a patient taking creatine.

PMID- 10075535
TI  - Detection of liver masses with spiral computed tomography.

PMID- 10075536
TI  - Patients with amyotrophic lateral sclerosis and physician-assisted suicide.

PMID- 10075537
TI  - Geography of U.S. biomedical publications, 1990 to 1997.

PMID- 10075538
TI  - Impostor phenomenon and queen bee syndrome: threats to success.

PMID- 10075539
TI  - Comparison of scores on two recent editions of the Developmental Test of Visual
      Motor Integration.
AB  - Standard scores on the third and fourth editions of the Developmental Test of
      Visual-motor Integration (VMI-3 and VMI-4) were compared for a sample of 120
      children (4-17 years of age) referred to an outpatient diagnostic clinic for
      developmental learning, attention, mood, and behavior problems. The two editions
      of the test have the same items, so the test was administered only once to each
      child, but the editions differ in their scoring systems and norms. The
      correlation between the pairs of standard scores on the two editions was .99, and
      the absolute mean difference between scores was only 1.5 points.

PMID- 10075540
TI  - Index of suspicion. Case 3. Atropine sulfate poisoning.

PMID- 10075541
TI  - Is prescribing antibiotics by phone for respiratory infections acceptable? This
      expert says yes!

PMID- 10075542
TI  - Genetic conflicts in genomic imprinting.
AB  - The expression pattern of genes in mammals and plants can depend upon the parent
      from which the gene was inherited, evidence for a mechanism of parent-specific
      genomic imprinting. Kinship considerations are likely to be important in the
      natural selection of many such genes, because coefficients of relatedness will
      usually differ between maternally and paternally derived genes. Three classes of
      gene are likely to be involved in genomic imprinting: the imprinted genes
      themselves, trans-acting genes in the parents, which affect the application of
      the imprint, and trnas-acting genes in the offspring, which recognize and affect
      the expression of the imprint. We show that coefficients of relatedness will
      typically differ among these three classes, thus engendering conflicts of
      interest between Imprinter genes, imprinted genes, and imprint-recognition genes,
      with probable consequences for the evolution of the imprinting machinery.

PMID- 10075543
TI  - Cistifolin, an integrin-dependent cell adhesion blocker from the anti-rheumatic
      herbal drug, gravel root (rhizome of Eupatorium purpureum).
AB  - During routine screening of medicinal plants for small molecular weight
      inhibitors of cell adhesion, the crude ethanolic extract of the anti-rheumatic
      herbal drug gravel root (rhizome of Eupatorium purpureum), was identified as a
      potent inhibitor of some beta 1 and beta 2 integrin-mediated cell adhesions. The
      active principle of gravel root has now been isolated and identified as 5-acetyl
      6-hydroxy-2,3-dihydro-cis-2-isopropenyl-3- tiglinoyloxybenzofuran (1). Compound 1
      inhibited integrin-dependent cell-cell and cell-protein interactions in vitro
      with EC50 values between 7-20 micrograms/ml. As with indomethacin, 1 administered
      orally two hours before induction of inflammation (in rat paw) by carrageenan
      inhibited oedema formation in a dose (10 and 50 mg/kg)-dependent manner. It
      appears that 1 has therapeutic potential for diseases where integrin adhesion
      molecules play a significant role.

PMID- 10075544
TI  - Megathyrin B: a cytotoxic diterpene from Isodon megathyrsus.
AB  - From the leaves of Isodon megathyrsus, a novel ent-kaurene diterpene, megathyrin
      B, was isolated and its structure determined as 1 alpha,7 beta,11 beta,15 beta
      tetrahydroxy-ent-7 alpha,20-epoxy-kaur-16-ene by 1D- and 2D-NMR spectral
      analysis. Additionally, its stereochemistry was unambiguously assigned by X-ray
      crystallography. This compound was cytotoxic to the KB and KB-V cell lines.

PMID- 10075546
TI  - Neuronal Degeneration and Regeneration: From Basic Mechanisms to Prospects for
      Therapy. Proceedings of the 20th International Summer School of Brain Research.
      Amsterdam, the Netherlands, 25-29 August 1997.

PMID- 10075545
TI  - A new bioactive norquinone-methide triterpene from Maytenus scutioides.
AB  - By antimicrobial and cytotoxic-guided fractionation, a bioactive norquinone
      methide triterpene, 15 alpha-hydroxypristimerin, was isolated from a South
      American medicinal plant, Maytenus scutioides. Its structure was determined on
      the basis of spectroscopic evidence. Successful chemical transformation of
      pristimerin to netzahualcoyene indicates that the 15-hydroxy compounds seems to
      be a possible percursor of 14(15)-ene-quinone-methide-triterpenoids in the
      biogenetic pathway.

PMID- 10075547
TI  - [VI Congress of Polish Society of Nephrology. Poznan, 24-26 September 1998.
      Proceedings and abstracts].

PMID- 10075548
TI  - Proceedings of the XIth International Expert Meeting of the Dr. Mildred Scheel
      Foundation for Cancer Research. Bonn, Germany, 16-17 November 1997.

PMID- 10075549
TI  - Retraction.

PMID- 10075550
TI  - Death to sperm mitochondria.

PMID- 10075551
TI  - The 1998 National Medal of Technology.

PMID- 10075552
TI  - French AIDS research pioneers to testify in trial of ministers.

PMID- 10075553
TI  - Cooking up sugar chains in a hurry.

PMID- 10075554
TI  - Scientific misconduct. Investigations on trial in a Texas court.

PMID- 10075555
TI  - Plan for divulging raw data eases fears.

PMID- 10075557
TI  - Environmental researchers wait anxiously for salvation.

PMID- 10075556
TI  - Cheap treatment cuts HIV transmission.

PMID- 10075558
TI  - Turtle origins.

PMID- 10075559
TI  - Unlimited mileage from telomerase?

PMID- 10075560
TI  - Researchers urged not to inject virulent HIV strain into chimps.

PMID- 10075561
TI  - Scientific misconduct. Baylor saga comes to an end.

PMID- 10075562
TI  - A gene that scrambles your heart.

PMID- 10075563
TI  - Virus suspect identified in elephant deaths.

PMID- 10075564
TI  - Preliminary data touch off genetic food fight.

PMID- 10075565
TI  - Planned chiropractic merger riles faculty.

PMID- 10075566
TI  - From junk bond king to cancer crusader.

PMID- 10075567
TI  - DNA sequences provide grist for microbiologists.

PMID- 10075568
TI  - Public access to data.

PMID- 10075569
TI  - Virulent HIV strains, chimpanzees, and trial vaccines.

PMID- 10075570
TI  - Molecules on a space odyssey.

PMID- 10075571
TI  - T cells and dendritic cells get intimate.

PMID- 10075572
TI  - Brain, heal thyself.

PMID- 10075573
TI  - MaRX: an approach to genetics in mammalian cells.

PMID- 10075574
TI  - Looking good from this window.

PMID- 10075575
TI  - Protein structure at your desk.

PMID- 10075576
TI  - Difference mapping cryo-EM.

PMID- 10075577
TI  - [Bronchial carcinoma developing in a tuberculous scar: computer tomographic
      follow up].
AB  - The development of scar is a rare complication of lung tuberculosis which was yet
      not often demonstrated in the radiologic literature. We report on a 71 year old
      male suffering by lung tuberculosis in an active stage which developed lung
      cancer in the region of tuberculotic scar clearly depicted on computed
      tomography. To the best of our knowledge this is the first reported computed
      computed tomography control series dealing with this problem. Additionally we
      report on histopathologic findings showing an early cancer in the surrounding of
      a tuberculotic scar.

PMID- 10075578
TI  - [Proceedings of the 2nd annual meeting in experimental and clinical pharmacology:
      melatonin. 27-29 November 1997].

PMID- 10075579
TI  - [Regulations on the production of expertise on material evidence in the forensic
      chemical laboratory departments of the Bureau of Forensic Medical Expertise.
      Appendix 6 to the order of the Ministry of Public Health of the Russian
      Federation of 10 December 1996 No. 407. Coordinated with the General Public
      Prosecutor, the Supreme Court and the Ministry of Internal Affairs of the Russian
      Federation].

PMID- 10075580
TI  - The mechanism of injury in a steatotic liver graft during cold preservation.
AB  - BACKGROUND: Fatty livers are more prone to primary nonfunction after
      transplantation. It is known that cell injury is strongly associated with
      alterations in the content and composition of membrane lipids. We assumed that
      plasma membrane (PM) fluidity, which is the most important property of the
      membrane, differed between fatty and normal livers. METHODS: The livers from
      obese and lean Zucker rats were flushed with cold Ringer's lactate and University
      of Wisconsin (UW) solution via the portal vein and preserved in cold UW solution
      for 24 hr. Histological examinations of electron microscopy were performed to
      investigate of sinusoidal lining cells (SLCs). PMs were isolated using a
      discontinuous density gradient of Percoll, and the lipid compositions were
      determined by chromatography. RESULTS: SLCs of fatty livers were markedly injured
      compared with control livers even after short preservation time. Moreover, many
      blebs were observed in the obese rats even after short preservation time. As for
      PM lipid composition, the cholesterol/phospholipid (PL) ratio of total PM was
      0.14+/-0.03 in the obese rats and 0.21+/-0.03 in the lean rats (P<0.05). The
      relative proportions of polyunsaturated fatty acids among PLs in PM were 35.7+/
      1.2% vs. 45.9+/-1.5% (P<0.0001). These results indicated that the fluidity of the
      PM in the obese rats is decreased after exposure to low temperatures.
      CONCLUSIONS: Our results suggest that steatotic livers from obese donors are more
      susceptible to cold preservation injury than livers without steatosis because of
      the severe deterioration of SLCs, and it is associated with PM fluidity even
      after short-term cold preservation.

PMID- 10075581
TI  - Ablating the ischemia-reperfusion injury in non-heart-beating donor kidneys.
AB  - BACKGROUND: The objective of this study was to determine if allopurinol (AL)
      and/or trifluoperazine (TFP) added to the Belzer machine preservation solution
      (MPS) improves the function of non-heart-beating donor (NHBD) canine kidneys.
      METHODS: Anesthetized canines underwent bilateral dissection of the renal
      vessels, obtaining baseline flow. After removing one kidney (heart-beating donor
      [HBD]), the dog was exsanguinated. After remaining in situ for 120 min (30-min
      warm ischemia time, 90-min cold ischemia time), the second kidney was removed
      (NHBD), flushed, biopsied, and weighed. The kidneys were machine-perfused
      separately for 20 hr, and pressure, flow, and resistance were measured serially.
      The kidneys were randomly assigned to a perfusate group (G): G1=MPS, G2=MPS+TFP,
      G3=MPS+AL, and G4=MPS+TFP+AL. Kidneys were implanted separately into a single
      recipient dog. Flow, resistance, and urine output were measured serially for 4
      hr. Blood and urine samples and kidney biopsies were then obtained. All
      measurements were standardized to 100 g of kidney weight. RESULTS: HBD kidneys
      functioned better than NHBD kidneys in all groups, as expected. Although
      perfusate G1 was the most effective solution for HBD kidneys, the TFP additive
      (perfusate G2) more effectively reversed the vasospastic effects of
      ischemia/reperfusion for NHBD than the MPS solution (G1) with or without other
      additives. In HBD kidneys, the addition of AL resulted in the best creatinine
      clearance; however, AL was less effective than MPS alone in NHBD kidneys. TFP+AL
      together were completely ineffective in preserving renal function, regardless of
      whether the kidneys were from HBD or NHBD. CONCLUSIONS: MPS+TFP more effectively
      protected renal function against reperfusion injury in the NHBD than MPS alone,
      AL, or AL+TFP. AL exerts a salutary effect on creatinine clearance in HBD but not
      in the NHBD. The TFP and AL combination should not be used together with the MPS
      in machine preservation of kidneys.

PMID- 10075582
TI  - Intragraft cytokine expression and tolerance induction in rat renal allografts.
AB  - BACKGROUND: Intragraft cytokine expression was evaluated in a model of renal
      transplantation. ACI and Lewis rats were used as donors and recipients,
      respectively, for heterotopic renal transplantation. METHODS: Treated allograft
      rats (n=10) received a preoperative dose of rapamycin and cyclosporine, followed
      by 7 days of cyclosporine postoperatively. Isograft rats (n=5) and control
      allograft rats (n=4) received no immunosuppression. Sacrifice was performed after
      120 days. Expression of interleukin (IL)-4, IL-10, and interferon-gamma (IFN
      gamma) transcripts was determined with semiquantitative reverse transcriptase
      polymerase chain reaction. RESULTS: All treated allograft rats had normal
      function with 50% histologic rejection. All isografts had normal function. IL-4
      and IL-10 were in greater density in allografts with normal histology, whereas
      IFN-gamma was only seen in allografts with cellular rejection. No IL-10 was seen
      in isografts, but IL-4 was detected in 3/5 isografts. CONCLUSIONS: We conclude
      that the lymphocyte population's elaboration of IL-4 and IL-10 is associated with
      tolerance, whereas the production of IFN-gamma and absence of IL-4 is associated
      with histology suggestive of acute cellular rejection.

PMID- 10075583
TI  - Induction of swine major histocompatibility complex class I molecules on porcine
      endothelium by tumor necrosis factor-alpha reduces lysis by human natural killer
      cells.
AB  - BACKGROUND: Natural killer (NK) cells have been implicated in a process of
      delayed xenograft rejection occurring in pig-to-primate organ transplants. As
      tumor necrosis factor-a (TNF-a) induces expression of both adhesion receptors and
      major histocompatibility complex class I molecules on porcine endothelium, we
      investigated the effects of TNF-alpha on human NK cell adherence to and
      cytotoxicity of porcine aortic endothelial cell (PAEC) monolayers. METHODS:
      Adherence of human NK cells was measured after PAEC treatment with increasing
      concentrations of TNF-alpha. Monoclonal antibodies (mAbs) against adhesion
      molecules on NK cells and PAEC were used in inhibition studies. Resting or TNF
      alpha-treated PAEC were used as targets for NK lysis. Increasing titers of anti
      swine leukocyte antigen (SLA) class I antibodies or pooled human immune globulin
      (IVIg) were used to reverse the effects of TNF-alpha on NK lysis. RESULTS: NK
      cell adhesion to TNF-a-treated PAEC increased in a dose-dependent manner by a
      maximum of 44%, and was inhibited by mAbs against CD49d, CD11a, CD11b, CD18, and
      CD2, as well as porcine vascular cell adhesion molecules. In contrast, TNF-alpha
      treatment of PAEC reduced human NK lysis in a dose-dependent manner.
      Preincubation of TNF-a-treated PAEC with increasing concentrations of anti-SLA
      class I mAb increased NK lysis in a titer-dependent manner, and reversed the
      protective effect on human NK lysis by 77%. Treatment with IVIg, containing
      antibodies against an a-helical region of HLA class I molecules, had a similar
      effect. CONCLUSIONS: These results imply that SLA class I molecules can bind to
      inhibitory receptors on human NK cells, and that these interactions can be
      augmented by increasing the level of SLA class I molecule expression on porcine
      endothelium. Strategies that can increase porcine endothelial cell expression of
      either swine or human major histocompatibility complex class I molecules may
      reduce human NK activity against porcine xenografts.

PMID- 10075584
TI  - High-level porcine endothelial cell expression of alpha(1,2)-fucosyltransferase
      reduces human monocyte adhesion and activation.
AB  - BACKGROUND: Monocyte binding to and activation by human endothelium requires a
      number of interactions, including those involving sialylated endothelial cell
      ligands. As porcine endothelial cell transfection with alpha(1,2)
      fucosyltransferase has been shown to reduce terminal sialylation, we investigated
      whether high-level expression of alpha(1,2)-fucosyltransferase by porcine
      endothelium would reduce human monocyte adhesion and functional activation.
      METHOD: Purified human monocytes were labeled with 51Cr, and measured for
      adherence to human or porcine endothelial cell monolayers in the presence of
      either medium or monoclonal antibodies against monocyte lectins or sialylated
      endothelial cell ligands. Monocyte production of prostaglandin E2 (PGE2) and
      interleukin-1beta (IL-1beta) was measured by enzyme-linked immunosorbent assay,
      using supernatants collected from cultures performed between human monocytes and
      human or porcine endothelial cell monolayers. Finally, monocyte adhesion and
      activation were measured after culture with a porcine endothelial cell line
      transfected with alpha(1,2)-fucosyltransferase, expressing reduced surface
      expression of terminal Gal alpha(1,3)-Gal and sialic acid residues. RESULTS:
      Human monocytes adhered by 50% higher levels to porcine endothelium than to human
      endothelium. This increased level of adherence was associated with augmented
      monocyte activation, as defined by 3.3-fold higher levels of PGE2 production and
      7.3-fold higher levels of IL-1beta production. Monoclonal antibodies against
      CD62L (L-selectin) on monocytes or CD15s (sialylated Lewis X) on porcine
      endothelium reduced monocyte adhesion by 38% and 52%, respectively. Porcine
      endothelial cell transfection with alpha(1,2)-fucosyltransferase reduced terminal
      sialic acid expression by 65%, monocyte adherence by 50%, and the production of
      PGE2 and IL-1beta by 67% and 38%, respectively. CONCLUSIONS: Together, these
      results demonstrate that human monocytes use surface lectins to bind to
      sialylated carbohydrate structures on porcine endothelium, and indicate that
      reduction in porcine endothelial cell surface expression of terminally sialylated
      structures by high-level alpha(1,2)-fucosyltransferase activity reduces monocyte
      adherence and activation.

PMID- 10075585
TI  - Regenerative signals for intestinal epithelial organoid units transplanted on
      biodegradable polymer scaffolds for tissue engineering of small intestine.
AB  - BACKGROUND: Our laboratory is investigating the tissue engineering of small
      intestine using intestinal epithelial organoid units seeded onto highly porous
      biodegradable polymer tubes. This study investigated methods of stimulation for
      optimizing neointestinal regeneration. METHODS: Intestinal epithelial organoid
      units harvested from neonatal Lewis rats were seeded onto porous biodegradable
      polymer tubes and implanted into the omentum of adult Lewis rats in the following
      groups: (1) the control group (group C), implantation alone (n=9); (2) the small
      bowel resection (SBr) group, after 75% SBr (n=9); (3) the portacaval shunt (PCS)
      group, after PCS (n=8); and (4) the partial hepatectomy (PH) group, after 75% PH
      (n=8). Neointestinal cyst size was recorded using ultrasonography. Constructs
      were harvested at 10 weeks and were examined using histology. Morphometric
      analysis of the neomucosa was obtained using a computer image analysis program
      (NIH Image, version 1.59). RESULTS: Cyst development was noted in all animals.
      Cyst lengths and diameters were significantly larger in the SBr group at 7 and 10
      weeks compared with the other three groups (P<0.05; analysis of variance [ANOVA],
      Fisher's protected least significant difference). Histology revealed a well
      vascularized tissue with a neomucosa lining the lumen with invaginations
      resembling crypt-villus structures. Morphometric analysis demonstrated a
      significantly greater villus number, height, area, and mucosal surface in the SBr
      group compared with the other three groups and a significantly greater crypt
      number and area in the PCS group compared with group C (P<0.05; ANOVA, Fisher's
      protected least significant difference). CONCLUSIONS: Intestinal epithelial
      organoid units transplanted on porous biodegradable polymer tubes can
      successfully vascularize, survive, and regenerate into complex tissue resembling
      small intestine. SBr and, to a lesser extent, PCS provide significant
      regenerative stimuli for the morphogenesis and differentiation of tissue
      engineered small intestine.

PMID- 10075586
TI  - Lung growth after reduced size transplantation in a sheep model.
AB  - BACKGROUND: The growth of mature allografts is a critical issue in pediatric lung
      transplantation. This study explores the architectural changes of mature sheep
      lung when submitted to two different compensatory growth forces: either
      transplantation into a neonatal host or expansion in an otherwise empty adult
      hemithorax. METHODS: Right upper lobes (RUL) (mean+/-SEM, 66.7+/-1.9 kg) from 4-
      to 5-year old (adult sheep) were transplanted into newborn (n=6) lambs (5.4+/-0.3
      kg, 5+/-2 days old) that were then allowed to survive for 45 days. Changes in
      pulmonary volume and architecture were measured before and after transplantation.
      Allografts were compared with both normal adult RUL (n=10) and adult (65.8+/-2.2
      kg and 4 to 5 year old) RUL that remained in situ for 45 days after resection of
      the corresponding middle and lower lobes (n=6). Statistical differences were
      analyzed using two-sample and paired t tests. RESULTS: In adult animals, RUL
      remaining in the otherwise empty hemithorax compensated by an 85% increase in
      volume (251.5+/-18.7 ml vs. 466+/-32.8 ml) (P<0.0001). Concomitant increases in
      total internal alveolar surface area (48%) and alveolar size were prominent. The
      number of alveoli per volume decreased proportionately to the increases in volume
      (P<0.0001). There was no significant change in the calculated number of alveoli
      (345.6+/-40.5 x 10(6)) compared with the normal adult RUL (402.4+/-40.7x10(6))
      (P=0.37). Transplant recipients received a reduced-size normal adult RUL (49%) in
      volume (125.3+/-21.5 ml). Allografts 45 days after transplantation showed a 73%
      increase in volume (216.4+/-21.3 ml) (P<0.0001) with a parallel (83%) increase in
      total internal alveolar surface area (P=0.008). The number of alveoli per volume
      remained constant (P=0.21) despite the increase in volume. There was therefore a
      significant increase in the calculated number of alveoli from before
      transplantation (172.5+/-35.9x 106) compared with that observed 45 days after
      transplantation (389.7+/-77.7x10(6)) (P=0.012). CONCLUSIONS: We conclude that
      mature sheep RUL parenchyma compensates with dilation of the respiratory
      structures in the adult animal, whereas there is alveolar multiplication when
      transplanted into newborn recipients.

PMID- 10075587
TI  - Successful anastomosis between tissue-engineered intestine and native small
      bowel.
AB  - BACKGROUND: Previous work from this laboratory has shown that isolated intestinal
      epithelial organoid units on porous biodegradable polymer scaffolds formed
      vascularized cysts lined by a neomucosa. The purpose of this study was to
      demonstrate anastomosis between tissue-engineered intestine and the native small
      bowel and to observe the effect of this anastomosis on cyst growth. METHODS:
      Intestinal epithelial organoid units from neonatal Lewis rats were seeded onto
      porous biodegradable polymer tubes made of polyglycolic acid, and they were
      implanted into the omentum of adult male Lewis rats. Three weeks after
      implantation, the unit-polymer constructs were anastomosed in a side-to-side
      fashion to the native jejunum in 20 rats (group 1). The other 18 rats were closed
      without anastomosis (group 2). All 38 tissue-engineered constructs were harvested
      10 weeks after implantation. Four rats underwent upper gastrointestinal (GI)
      study before they were killed. RESULTS: The rats in group 1 increased their body
      weights equal to those in group 2, and there was no statistically significant
      difference between the two groups. Upper GI examinations revealed no evidence of
      either bowel stenosis or obstruction at the anastomotic site. Grossly, the
      patency of the anastomosis was 90% and the lumen of the cyst was visualized by
      the upper GI study. At the second operation, there was no significant difference
      in the size of the cysts in either group: however, at the time the rats were
      killed, the length of the cysts in group 1 was significantly longer than that in
      group 2 (P<0.05 using Mann-Whitney U test). Histological examination showed that
      cysts after anastomosis were lined by a neomucosa in continuity to native small
      bowel across the anastomotic site and also demonstrated crypt-villus structures.
      Morphometric study demonstrated that cysts in group 1 had significantly greater
      villus number, height, and surface length than did those in group 2. CONCLUSIONS:
      Anastomosis between tissue-engineered intestine and native small bowel resulted
      in no complications after the operation, kept a high patency rate, and maintained
      mucosal continuity between the tissue-engineered intestine and native small
      bowel. Furthermore, anastomosis had a positive effect on cyst size and
      development of the mucosa in the tissue-engineered intestine.

PMID- 10075588
TI  - Evolving trends in liver transplantation: an outcome and charge analysis.
AB  - BACKGROUND: Due to the limited supply and increased demand for donor livers,
      waiting times are progressively lengthening, which may lead to transplantation at
      more advanced and less cost-effective stages of disease. The purpose of this
      study was to evaluate the outcomes and hospital charges of liver transplantation
      during two recent eras to identify areas for providing more cost-effective care.
      METHODS: A total of 144 primary liver allografts were performed from 1991 to
      1996. Patient characteristics, outcome measures, and hospital charges were
      compared for patients receiving allografts between 1991 and 1993 (group A) versus
      those receiving grafts between 1994 and 1996 (group B) using unpaired Student t
      tests for continuous data and chi-squared tests for categorical data. RESULTS: In
      comparing groups A and B, no significant differences in patient demographics,
      relative contraindications, or indication for transplantation existed; median
      waiting time from date of listing until transplant increased from 88 days to 159
      days; and a shift in UNOS priority status at time of transplantation occurred, as
      the percentage of patients requiring inpatient care increased from 58% to 75%
      (P=0.034). Despite this, patient hospital and 1-year survival significantly
      improved from 75.0% to 90.3% (P=0.016), and from 68.1% to 88.9% (P=0.002),
      respectively. Total hospital charges, without correction for inflation, were
      $174,908+/-16,388 in A and $193,525+/-14,444 in B (P=0.288). The increased
      charges were associated with longer inpatient length of stay (LOS) before
      transplant, resulting in increased pretransplant charges from $24,088+/-4134 (A)
      to $39,490+/-6,196 (B) (P=0.011). Room and service (54%) was the largest
      pretransplant contributor to charges, while blood products (23%), room and
      service (21%), organ acquisition (13%), and operating room charges (11%)
      contributed the most after transplant. CONCLUSIONS: Longer waiting times
      resulting in transplantation at later stages of disease have occurred, leading to
      longer pretransplant LOS and its associated charges. Despite more advanced
      disease, patient survival rates have significantly improved with fewer infection
      related deaths. LOS pretransplant, blood products, and operating room services
      represent potential areas for providing more cost-effective care.

PMID- 10075589
TI  - In vivo generation of C4d, Bb, iC3b, and SC5b-9 after OKT3 administration in
      kidney and lung transplant recipients.
AB  - BACKGROUND: OKT3 monoclonal antibody therapy results in an acute clinical
      syndrome (ACS) associated with the release of tumor necrosis factor and
      sequestration of neutrophils in the lungs. We have previously shown that
      inhibition of tumor necrosis factor does not completely eliminate OKT3-ACS,
      suggesting that other factors also contribute to the ACS. The current studies
      analyzed complement activation in vivo during the first hour after OKT3
      administration. METHODS: Renal (n=4) and lung (n=4) transplant recipients
      received OKT3 as treatment for rejection and induction therapy, respectively.
      Complement activation products C4d, Bb, iC3b, and SC5b-9 were measured by ELISA.
      Hemodynamic parameters were also monitored in the lung transplant recipients.
      Neutrophil expression of CD11a, CD11b, and CD18 was monitored by flow cytometry.
      Controls included patients receiving methylprednisolone for rejection (n=4), two
      adults with adult respiratory distress syndrome who received extracorporeal
      membrane oxygenation, and normal volunteers (n=5). P values less than 0.05 (*)
      were considered significant. RESULTS: Increases in the plasma levels of C4d, Bb,
      iC3b, and SC5b-9 were observed in seven of eight patients after OKT3
      administration. Mean values (n=8) at 0, 15, and 60 min (in microg/ml) were as
      follows-C4d: 1.865, 2.644*, and 2.607*; Bb: 0.245, 0.411, and 0.385; iC3b:
      10.881, 17.242*, and 15.145*; and SC5b-9: 0.232, 0.269, and 0.302*. An increase
      in CD11b and CD18 and a decrease of CD11a on neutrophils in parallel with
      complement activation was observed. In lung transplant recipients, C3 activation
      correlated with increases in mean pulmonary and central venous pressures
      (P<0.05). As compared with extracorporeal membrane oxygenation, which activated
      classical and alternative pathways, OKT3 predominantly activated complement by
      the classical pathway. Methylprednisolone pulses did not activate complement.
      CONCLUSIONS: Complement activation is an early event after OKT3 administration
      and is associated with the increased expression of adhesion molecules on
      neutrophils and with pulmonary hemodynamic changes. Effective therapeutic
      approaches to the control of early monoclonal antibody side effects may require
      measures that limit complement activation in addition to reducing cytokine
      activity.

PMID- 10075590
TI  - The role of flow cytometry-detected IgG and IgM anti-donor antibodies in cardiac
      allograft recipients.
AB  - BACKGROUND: At our transplant center, cardiac allograft recipients undergo
      transplantation following a negative IgG anti-human globulin (AHG) crossmatch
      (XM). Flow cytometry crossmatching (FCXM) is a more sensitive XM procedure than
      the AHG XM procedure, yet there is limited information regarding the clinical
      relevance of FCXM to cardiac allograft outcome. METHODS: FCXM was performed
      retrospectively using the pretransplant sera from 140 recipients of primary
      cardiac allografts who underwent transplantation after AHG-IgG-NEG XM. The FCXM
      results were correlated to posttransplant rejection and patient survival.
      RESULTS: All of the patients were auto-XM-NEG. Twenty-two of 140 patients (16%)
      displayed IgG(+) FCXM and had a significantly poorer 1-year survival rate than
      did 57 of the FCXM-NEG recipients (68% vs. 86%, P<0.02). Moreover, 50% of the
      IgG(+) FCXM recipients experienced early rejections (< or =14 days
      postoperatively) compared with only 16% for the FCXM-NEG recipients (P<0.01). The
      survival rate of 92% for IgM(+) FCXM recipients (n=37) was significantly improved
      compared with the 86% survival rate for FCXM-NEG control recipients (P<0.05),
      suggesting a protective role for IgM. Consistent with this interpretation is that
      the 1-year survival rate of 79% for the IgG, IgM FCXM(+) recipients (n=24) was
      significantly better than the 68% survival rate for the IgG(+) FCXM recipients
      (P<0.02). CONCLUSIONS: These data suggest that IgG(+) FCXM identifies a subset of
      AHG-IgG-NEG XM cardiac allograft recipients who are at risk for early rejections
      and poor survival. In contrast, the presence of IgM may be beneficial to
      survival.

PMID- 10075591
TI  - Increased incidence of gastrointestinal surgical complications in renal
      transplant recipients with polycystic kidney disease.
AB  - BACKGROUND: We had the impression that, although our renal transplant recipients
      with polycystic kidney disease (PKD) had excellent long-term renal graft
      function, they had an increased incidence of postoperative gastrointestinal (GI)
      complications. METHODS: Over a 10-year period (1987 through 1996), 1467 renal
      transplants were performed in 1417 patients; 145 of these transplants involved
      PKD recipients. In the PKD group, 18 patients (12.4%) developed a posttransplant
      complication necessitating GI surgery (PKD-GI), an incidence twice that in the
      non-PKD recipients (73 patients or 6.2%, non-PKD-GI). RESULTS: PKD and non-PKD
      recipients displayed no significant difference in mortality. The PKD patients had
      better long-term renal graft survival than the non-PKD patients (P=0.08). There
      was no difference in mortality (P>0.6) or renal graft survival (P>0.6) between
      the PKD-GI and PKD-non-GI groups. The PKD-GI group had no increased mortality
      over the non-PKD-GI patients (P>0.6), despite a higher incidence of GI surgical
      complications in the PKD group versus the non-PKD group (overall: 12.4 vs. 6.2%,
      P<0.01; within 90 days of transplant: 7.6 vs. 3.3%, P<0.02) and a greater
      propensity for small and large bowel complications (overall: 9.0 vs. 2.6%; P<
      0.001; less than 90 days: 6.9 vs. 2.0%, P<0.002). The PKD-GI recipients tended
      toward less long-term graft loss than their non-PKD-GI counterparts (11.1 vs.
      27.4%; P=.22). The PKD-GI recipients suffered no acute rejection episodes within
      90 days after their GI operation versus 11 of 73 non-PKD-GI recipients (O vs.
      15.1%; P=0.075). CONCLUSIONS: PKD recipients of renal grafts should be watched
      closely early after transplant because of their increased risk of GI
      complications. These complications resulted in no increase in mortality or graft
      loss compared to non-PKD recipients with GI complications despite the PKD group's
      higher incidence of bowel perforation and increased age at time of transplant.

PMID- 10075593
TI  - Chronic viral hepatitis in renal transplant recipients with allografts
      functioning for more than 20 years.
AB  - BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus
      [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft
      function in renal transplant recipients with allografts functioning for >20 years
      is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants
      performed at the Cleveland Clinic Foundation from January 1963 to January 1978
      are known to have functioned for at least 20 years (level 5A). Fifty-four of
      these patients had hepatitis testing updated after their 19th year of
      transplantation. Fifteen patients had evidence of ongoing viral infection:
      persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked
      immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%),
      and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further
      for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was
      positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An
      elevated alanine aminotransferase (>35 U/L) was present in all hepatitis
      patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50
      microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was
      detected by hepatic ultrasound. In patients with chronic viral hepatitis,
      probable cirrhosis developed in 20% (3/15) compared to one patient in the group
      without hepatitis, but there was no mortality from liver failure in either group.
      Diabetes mellitus was significantly more common in those with than without
      hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs.
      15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from
      meningitis, one from unknown cause, and three from coronary heart disease [CHD]
      vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more
      frequent occurrence of CHD among those with hepatitis was not significant (7/15
      vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly
      increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected
      with hepatotropic viruses (HBV and HCV) have a high rate of active viral
      replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall
      mortality (P=0.014).

PMID- 10075592
TI  - Long-term results of pancreas transplantation under tacrolius immunosuppression.
AB  - BACKGROUND: The long-term safety and efficacy of tacrolimus in pancreas
      transplantation has not yet been demonstrated. The observation of prolonged
      pancreatic graft function under tacrolimus would indicate that any potential
      islet toxicity is short-lived and clinically insignificant. We report herein the
      results of pancreas transplantation in patients receiving primary tacrolimus
      immunosuppression for a minimum of 2 years. METHODS: From July 4, 1994 until
      April 18, 1996, 60 patients received either simultaneous pancreas-kidney
      transplant (n=55), pancreas transplant only (n=4), or pancreas after kidney
      transplantation (n=1). Baseline immunosuppression consisted of tacrolimus and
      steroids without antilymphocyte induction. Azathioprine was used as a third agent
      in 51 patients and mycophenolate mofetil in 9. Rejection episodes within the
      first 6 months occurred in 48 (80%) patients and were treated with high-dose
      corticosteroids. Antilymphocyte antibody was required in eight (13%) patients
      with steroid-resistant rejection. RESULTS: With a mean follow-up of 35.1+/-5.9
      months (range: 24.3-45.7 months), 6-month and 1-, 2-, and 33-year graft survival
      is 88%, 82%, 80%, and 80% (pancreas) and 98%, 96%, 93%, and 91% (kidney),
      respectively. Six-month and 1-, 2-, and 3-year patient survival is 100%, 98%,
      98%, and 96.5%. Mean fasting glucose is 91.6+/-13.8 mg/dl, and mean glycosylated
      hemoglobin is 5.1+/-0.7% (normal range: 4.3-6.1%). Mean tacrolimus dose is 6.5+/
      2.6 mg/day and mean prednisone dose 2.0+/-2.9 mg/day at follow-up. Complete
      steroid withdrawal was possible in 31 (65%) of the 48 patients with functioning
      pancreases. CONCLUSIONS: These data show for the first time that tacrolimus is a
      safe and effective long-term primary agent in pancreas transplantation and
      provides excellent long-term islet function without evidence of toxicity while
      permitting steroid withdrawal in the majority of patients.

PMID- 10075594
TI  - Reduction of the occurrence of acute cellular rejection among renal allograft
      recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor
      monoclonal antibody. United States Simulect Renal Study Group.
AB  - BACKGROUND: A double-blind, placebo-controlled phase III study was performed to
      assess whether basiliximab, a chimeric anti-interleukin-2 receptor monoclonal
      antibody, reduced the incidence of acute rejection episodes in renal allograft
      recipients. METHODS: A total of 348 patients were randomized into two
      demographically matched, equally sized groups treated with either basiliximab or
      placebo. The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected
      to block detection of interleukin-2 receptor on 97% of peripheral blood
      lymphocytes for 30-45 days. All patients received immunosuppressive therapy with
      cyclosporine microemulsion (Neoral) and steroids. An intent-to-treat analysis of
      1-year data assessed the incidence of posttransplant acute rejection episodes,
      patient and graft survival rates, and the safety and tolerability of basiliximab.
      RESULTS: Among the eligible 346 patients equally divided into the two treatment
      groups, basiliximab reduced the proportion of patients who experienced biopsy
      confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab vs. 85 (49.1%)
      placebo (P=0.009). Graft losses occurred in 9 (5.2%) basiliximab-treated and 12
      (6.9%) placebo-treated patients. Five (2.9%) deaths in the basiliximab group and
      seven (4.0%) in the placebo group occurred. Compared with placebo, a higher
      fraction of basiliximab patients produced urine in the operating room, and a
      significantly lower fraction had renal dysfunction in the first month (serum
      creatinine > or =5 mg(dl) and between 1 and 12 months (serum creatinine > or =3
      mg/dl). During the first 12 months, 94 (54%) basiliximab-treated patients
      experienced serious adverse events, compared with 106 (61%) who received placebo.
      CONCLUSIONS: Prophylactic basiliximab therapy is well tolerated, has an adverse
      event profile comparable to placebo, and significantly reduces the number of
      acute rejection episodes in renal allograft patients within the first year after
      transplantation.

PMID- 10075595
TI  - Strategies to expand the donor pool for pancreas transplantation.
AB  - BACKGROUND: Our organ procurement organization has been forced to liberalize the
      donor criteria in order to expand the donor pool for pancreas transplantation. In
      this report, we describe our experience using whole organ pancreatic grafts from
      "marginal" donors, which include grafts obtained from donors over 45 years of age
      and from donors who were identified to be hemodynamically unstable at the time of
      organ retrieval. METHODS: A prospective study was performed between July 1994 and
      March 1998, during which time 137 pancreas transplants were performed at our
      center using organs procured by our own surgeons (organs sent by other teams were
      excluded). The rapid en bloc technique was used exclusively. The use of
      pancreatic grafts from marginal donors was analyzed for short-term and overall
      graft survival, and for delayed graft function and complications. RESULTS:
      Overall pancreas graft survival for our series was 83%, with a mean follow-up of
      23 months. There were 22 pancreas grafts from donors over 45 years of age, 13 of
      whom were greater than 50 years of age. The actual graft survival rate of the
      over-45 donor group was 86%. Fifty-one grafts were removed from hemodynamically
      unstable donors on high-dose vasopressors. The actual graft survival in this
      group was 86%. There was no significant difference found in graft survival
      between recipients of pancreatic grafts from marginal and nonmarginal donors.
      Delayed graft function was exhibited by more recipients of grafts from donors on
      high-dose vasopressors (P<0.05), but this had no effect on long-term graft
      survival and endocrine function. Recipients of marginal donor grafts did not have
      higher rates of complication compared to recipients of nonmarginal grafts.
      CONCLUSIONS: Based on our results, we currently employ a graft selection strategy
      not limited by donor age or hemodynamic stability. Our selection of pancreas
      organs for transplantation is based on careful inspection of the pancreas and
      determination of the adequacy of the ex vivo flush. Our results suggest that the
      current pancreas donor pool may be expanded substantially.

PMID- 10075596
TI  - Renal transplantation in end-stage sickle cell nephropathy.
AB  - BACKGROUND: The role of renal transplantation as treatment for end-stage sickle
      cell nephropathy (SCN) has not been well established. METHODS: We performed a
      comparative investigation of patient and allograft outcomes among age-matched
      African-American kidney transplant recipients with ESRD as a result of SCN (n=82)
      and all other causes (Other-ESRD, n=22,565). RESULTS: The incidence of delayed
      graft function and predischarge acute rejection in SCN group (24% and 26%) was
      similar to that observed in the Other-ESRD group (29% and 27%). The mean
      discharge serum creatinine (SCr) was 2.7 (+/-2.5) mg/dl in the SCN recipients
      compared to 3.0 (+/-2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was
      no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD:
      77%), and the multivariable adjusted 1-year risk of graft loss indicated no
      significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year
      cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%,
      P=0.055) and their adjusted 3-year risk of graft loss was significantly greater
      (RR= 1.60, P=0.003). There was a trend toward improved survival in the SCN
      transplant recipients compared to their dialysis-treated, wait-listed
      counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the
      adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95,
      P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation.
      CONCLUSIONS: The short-term renal allograft result in recipients with end-stage
      SCN was similar to that obtained in other causes of ESRD, but the long-term
      outcome was comparatively diminished. There was a trend toward better patient
      survival with renal transplantation relative to dialysis in end-stage SCN.

PMID- 10075597
TI  - Bacillary angiomatosis in a renal transplant recipient.
AB  - A case of bacillary angiomatosis infection presenting as a skin nodule in a renal
      transplant recipient was found. The patient was taking cyclosporine, prednisone,
      and mycophenolate mofetil at the time of presentation. The bacillary angiomatosis
      responded to 6 months of therapy with oral erythromycin.

PMID- 10075599
TI  - A new allocation plan for renal transplantation.
AB  - BACKGROUND: A novel plan of renal allograft allocation has been conducted by
      United Network for Organ Sharing Region 1 transplant centers since September 3,
      1996, based upon HLA matching, time waiting, and population distance points. The
      objectives of this plan were to achieve a balance between increasing the
      opportunity of renal transplantation for those patients listed with long waiting
      times and promoting local organ donor availability. METHODS: A single list of
      candidates was formulated for each cadaver donor, assigning a maximum of 8 points
      for time waiting, a maximum of 8 points for population distance from the donor
      hospital, and HLA points based upon the degree of B/DR mismatch. Additional
      points were awarded to a cross-match-negative patient with a panel-reactive
      antibody of >80%, and to pediatric patients. RESULTS: The total number of kidneys
      transplanted to patients who had waited >3 years was 100 (46%), and to patients
      who had waited >2.5-3 years was 29 (13%). However, the total number of kidneys
      transplanted to patients with the maximum population distance points was only 72
      (33%). Thus, although the plan achieved a favorable distribution of kidneys to
      patients with longer waiting times (nearly 60%), the other, equally important
      objective of promoting local donor availability was not initially accomplished.
      Moreover, minor HLA B/DR differences between the donor and the recipient (i.e.,
      not phenotypically matched) were unexpectedly consequential in determining
      allocation. As a result of these observations, the following adjustments were
      made in the plan (as of December 3, 1997): a maximum of 10 points for population
      distance, a maximum of 8 points for time waiting (both by a linear correlation),
      and the retention of HLA points for 0 B/DR mismatch only. After these interval
      changes, the percentage of patients receiving a kidney with some population
      distance points increased from 85% to 96%. Conclusions. We have shown that a
      heterogeneous region of multiple transplant centers can devise (and modify) an
      innovative and balanced plan that provides an equitable system of allocation for
      an ever-increasing number of patients.

PMID- 10075598
TI  - Pediatric renal transplantation under tacrolimus-based immunosuppression.
AB  - BACKGROUND: Tacrolimus has been used as a primary immunosuppressive agent in
      adult and pediatric renal transplant recipients, with reasonable outcomes.
      Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal
      transplantations alone were performed under tacrolimus-based immunosuppression
      without induction anti-lymphocyte antibody therapy. Patients undergoing
      concomitant or prior liver and/or intestinal transplantation were not included in
      the analysis. The mean recipient age was 10.6+/-5.2 years (range: 0.7-17.9).
      Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients
      with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with
      living donors, and 48 (59%) were with cadaveric donors. The mean donor age was
      27.3+/-14.6 years (range: 0.7-50), and the mean cold ischemia time in the
      cadaveric cases was 26.5+/-8.8 hr. The mean number of HLA matches and mismatches
      was 2.8+/-1.2 and 2.9+/-1.3; there were five (6%) O-Ag mismatches. The mean
      follow-up was 4.0+/-0.2 years. RESULTS: The 1- and 4-year actuarial patient
      survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and
      84%. The mean serum creatinine was 1.1+/-0.5 mg/dl, and the corresponding
      calculated creatinine clearance was 88+/-25 ml/min/1.73 m2. A total of 66% of
      successfully transplanted patients were withdrawn from prednisone. In children
      who were withdrawn from steroids, the mean standard deviation height scores (Z
      score) at the time of transplantation and at 1 and 4 years were -2.3+/-2.0, 
      1.7+/-1.0, and +0.36+/-1.5. Eighty-six percent of successfully transplanted
      patients were not taking anti-hypertensive medications. The incidence of acute
      rejection was 44%; between December 1989 and December 1993, it was 63%, and
      between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of
      steroid-resistant rejection was 5%. The incidence of delayed graft function was
      5%, and 2% of patients required dialysis within 1 week of transplantation. The
      incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it
      was 17%, and between January 1993 and December 1996, it was 12%. The incidence of
      early Epstein-Barr virus-related posttransplant lymphoproliferative disorder
      (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between
      January 1993 and December 1996, it was 4%. All of the early PTLD cases were
      treated successfully with temporary cessation of immunosuppression and
      institution of antiviral therapy, without patient or graft loss. CONCLUSIONS:
      These data demonstrate the short- and medium-term efficacy of tacrolimus-based
      immunosuppression in pediatric renal transplant recipients, with reasonable
      patient and graft survival, routine achievement of steroid and anti-hypertensive
      medication withdrawal, gratifying increases in growth, and, with further
      experience, a decreasing incidence of both rejection and PTLD.

PMID- 10075600
TI  - IgA class antibodies and flow cytometric cross-matching in renal transplantation.
AB  - BACKGROUND: The established method of pretransplant cross-matching does not
      detect IgA antibodies, and IgA antibodies have thus been ignored when assessing
      patients for transplantation. The aim of this study was to detect IgA allo- and
      autoreactive antibodies using flow cytometry and to correlate the results with
      transplant outcome. METHODS: Pretransplant sera from 231 sequential renal
      recipients were tested for serum IgA levels and antibodies directed against the
      Fab portion of the human IgG molecule. Fifty-nine recipients with sufficient
      stored donor lymphocytes were also tested by flow cytometry for donor-specific
      alloantibodies of the IgA isotype. RESULTS: Graft survival was improved in
      recipients with higher IgA levels. High IgA anti-Fab levels led to a
      significantly higher 1-year graft survival (P<0.05). Graft survival was further
      enhanced where both serum IgA and IgA anti-Fab were raised (P<0.01). Although the
      mean IgA level tended to be higher for recipients with a positive IgA flow
      cytometric cross-match (FCXM), the IgA FCXM was not associated with increased IgA
      anti-Fab, suggesting that the IgA FCXM is detecting a different subset of IgA
      reactivity. Additionally, for primary grafts, a positive IgA FCXM was not
      associated with enhanced graft survival. CONCLUSIONS: Within the repertoire of
      IgA activity, there are two recognizable groups, the IgA anti-Fab specificity,
      which is significantly associated with enhanced graft survival, and that detected
      by the IgA FCXM, which surprisingly is more likely to be positive in less
      sensitized first grafts and is not associated with enhanced graft survival.

PMID- 10075601
TI  - Efficacy and cost effectiveness of oral ganciclovir in the prevention of
      cytomegalovirus disease after lung transplantation.
AB  - BACKGROUND: Cytomegalovirus is the single most frequent pulmonary pathogen in
      lung transplant recipients who survive at least 2 weeks. Patients at increased
      risk are either seropositive or have received an allograft from a donor with
      latent infection. Morbidity and mortality caused by cytomegalovirus disease is
      still considerably high. METHODS: In an open, comparative study, we evaluated the
      efficacy, tolerance, and cost effectiveness of postoperative ganciclovir
      prophylaxis: intravenous dose of 2x5 mg/kg/day for 14 days, followed by either
      intravenous doses of 5 mg/kg]day (five patients), or oral doses of 3x 1000 mg
      (nine patients) up to 90 days. Oral ganciclovir was continued until prednisone
      was tapered below 15 mg/day. Prophylaxed groups were compared with a historical
      control (eight patients) in respect to cytomegalovirus disease, in-hospital stay,
      overall costs, and survival. Follow-up times and the net state of
      immunosuppressive therapy between groups were comparable. RESULTS: Six (75%) of
      the non-prophylaxed patients developed cytomegalovirus disease compared to none
      in the intravenous and one in the oral ganciclovir group (P=0.013). The non
      prophylaxed patients had a longer cytomegalovirus-related in-hospital stay
      (P=0.018) and nonsignificantly higher cytomegalovirus-related costs.
      Bronchiolitis obliterans syndrome was less frequent with prophylaxis (P=0.039),
      and survival tended to be better (P=0.072). The only adverse effect was a
      subclavian vein thrombosis in the intravenous ganciclovir group. CONCLUSIONS: In
      lung transplant recipients, ganciclovir prophylaxis, either intravenous or oral,
      is safe, well tolerated, and effective in preventing cytomegalovirus disease.
      Moreover, ganciclovir prophylaxis seems likely to reduce the incidence of
      bronchiolitis obliterans syndrome. The oral formulation might be preferable
      because its convenience and possibly lower costs.

PMID- 10075602
TI  - Impact of graft size mismatching on graft prognosis in liver transplantation from
      living donors.
AB  - BACKGROUND: Although living donor liver transplantation for small pediatric
      patients is increasingly accepted, its expansion to older/larger patients is
      still in question because of the lack of sufficient information on the impact of
      graft size mismatching. METHODS: A total of 276 cases of living donor liver
      transplantation, excluding ABO-incompatible, auxiliary, or secondary transplants,
      were reviewed from graft size matching. Forty-three cases were highly urgent
      cases receiving intensive care preoperatively. Cases were categorized into five
      groups by graft-to-recipient weight ratio (GRWR): extra-small-for-size (XS;
      GRWR<0.8%, 17 elective and 4 urgent cases), small (S; 0.8< or =GRWR< 1.0%, 21 and
      7), medium (M; 1.0< or =GRWR<3.0%, 119 and 19), large (L; 3.0< or =GRWR<5.0%, 67
      and 10), and extra-large (XL; GRWR> or =5.0%, 9 and 3). RESULTS: Smaller-for-size
      grafts were associated not only with larger and older recipients, but also with
      rather older donors. Posttransplant bilirubin clearance was delayed and aspartate
      aminotransferase corrected by relative graft size was higher in XS and S.
      Posttransplant hemorrhage and intestinal perforation were more frequent in XS and
      S, and vascular complications and acute rejection were more frequent in larger
      for-size grafts. Consequently, graft survival in XS (cumulative 58% and actuarial
      42% at 1 year) and S (76% and 74%) was significantly lower compared with that in
      M (93% and 92%) in elective cases. Graft survival in L (83% and 82%) and XL (75%
      and 71%) did not reach statistical significance. CONCLUSIONS: The use of small
      for-size grafts (less than 1% of recipient body weight) leads to lower graft
      survival, probably through enhanced parenchymal cell injury and reduced metabolic
      and synthetic capacity. Although large-for-size grafts are associated with some
      anatomical and immunological disadvantages, the negative impact is less
      pronounced.

PMID- 10075603
TI  - Endothelin antagonist treatment for successful liver transplantation from non
      heart-beating donors.
AB  - BACKGROUND: With the shortage of cadaveric donors, non-heart-beating donors
      (NHBDs) are a potential source of liver allografts. However, warm ischemic injury
      in NHBDs seriously affects the viability of graft liver. Endothelin (ET)-1 has
      been reported to be involved in the hepatic microcirculatory disturbances after
      ischemia-reperfusion. METHODS: In a porcine orthotopic liver transplantation
      model, changes in the serum and liver tissue ET-1 concentration were measured and
      the effects of an ET receptor antagonist, TAK-044, were evaluated. After cardiac
      arrest of the donors, liver allografts were subjected to 90 min of warm ischemia,
      flushed, and preserved for 4 hr at 4 degrees C. The pigs were divided into two
      groups: a control group (no drug treatment) and a drug-treated group, in which
      donors and recipients were treated with TAK-044 (10 mg/kg body, drip intravenous
      injection). Both groups had six donor/recipient pairs. RESULTS: -The ET-1
      concentration in the hepatic venous blood increased after reperfusion of the
      graft in the control group recipients. ET-1 in the graft liver significantly
      increased during the cold preservation period. TAK-044 treatment significantly
      increased recipient 7-day survival rate. After reperfusion of the graft, the
      concentrations of serum liver enzymes and arterial lactate in the drug-treated
      group were significantly lower than in the control group. The postoperative
      increase in portal venous pressure was significantly reduced in the drug-treated
      group. Measurements of liver enzymes in the washed-out preservation fluid at the
      time of graft rinsing indicated that TAK-044 treatment of the donors
      significantly suppressed liver enzyme release during ischemia. CONCLUSIONS: These
      findings indicate TAK-044 treatment has protective effects on postoperative
      function of hepatic allografts procured from NHBDs.

PMID- 10075604
TI  - Low bioavailability of cyclosporine microemulsion and tacrolimus in a small bowel
      transplant recipient: possible relationship to intestinal P-glycoprotein
      activity.
AB  - With intestine transplants the allograft is dependent on itself for maintenance
      of adequate immunosuppression. We evaluated an intestinal transplant recipient
      who required very large doses of either tacrolimus or cyclosporine emulsion to
      achieve acceptable blood concentrations. Pharmacokinetic studies revealed
      bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption
      were found to be within normal limits and fecal fat was only slightly increased,
      suggesting that there was a selective absorptive defect for these drugs. Biopsies
      of the allograft ileum revealed a high P-glycoprotein activity compared to the
      jejunum or to intestinal biopsies from other normal subjects. This may be a
      contributing factor to poor immunosuppressive drug absorption in this patient and
      others.

PMID- 10075605
TI  - Exchange donor program in kidney transplantation.
AB  - The donor organ shortage has been one of the major barriers to kidney
      transplantation in Korea, even though there has been a small but steady flow of
      cadaveric kidney donations for the last decade. To expand the donor pool in
      kidney transplantation, we have developed the exchange donor program at our
      institution and in Korea. The donor exchange program was first started for end
      stage renal disease patients who had willing but incompatible related donors due
      to positive lymphocyte cross-match. The kidney transplantations were performed
      using exchanged kidneys between two families with successful results. Since this
      success, we have expanded the donor pool by accepting close relatives, spouses,
      friends of recipients, and willing voluntary donors as candidates for exchange
      donors with careful donor screening procedures. It helps relieve stress on donor
      supply. Particularly in those countries where brain death has not been socially
      or legally accepted, living donors including related, unrelated, and exchange
      donors should be considered as potential donors for kidney transplantation to
      relieve the pressure on donor organ shortage.

PMID- 10075606
TI  - Peripheral blood stem cells from unrelated donors for allogeneic transplantation.

PMID- 10075607
TI  - In memoriam: Lindsay M. Black (1907-1997).

PMID- 10075608
TI  - Tips for aspiring article writers.

PMID- 10075609
TI  - Electronic communication and discussion forums: news groups and mailing lists.

PMID- 10075610
TI  - 1998 ASHG Award for Excellence in Education. Professor Ching Chun Li, courageous
      scholar and educator.

PMID- 10075611
TI  - 1998 ASHG Award for Excellence in Education. Remarks on receiving the ASHG award:
      science and science education.

PMID- 10075612
TI  - [Regulations for intravenous injections and blood specimen collection].

PMID- 10075613
TI  - A more accurate method to estimate glomerular filtration rate from serum
      creatinine: a new prediction equation. Modification of Diet in Renal Disease
      Study Group.
AB  - BACKGROUND: Serum creatinine concentration is widely used as an index of renal
      function, but this concentration is affected by factors other than glomerular
      filtration rate (GFR). OBJECTIVE: To develop an equation to predict GFR from
      serum creatinine concentration and other factors. DESIGN: Cross-sectional study
      of GFR, creatinine clearance, serum creatinine concentration, and demographic and
      clinical characteristics in patients with chronic renal disease. PATIENTS: 1628
      patients enrolled in the baseline period of the Modification of Diet in Renal
      Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample;
      the remaining 558 patients constituted the validation sample. METHODS: The
      prediction equation was developed by stepwise regression applied to the training
      sample. The equation was then tested and compared with other prediction equations
      in the validation sample. RESULTS: To simplify prediction of GFR, the equation
      included only demographic and serum variables. Independent factors associated
      with a lower GFR included a higher serum creatinine concentration, older age,
      female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower
      serum albumin levels (P < 0.001 for all factors). The multiple regression model
      explained 90.3% of the variance in the logarithm of GFR in the validation sample.
      Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance
      predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After
      adjustment for this overestimation, the percentage of variance of the logarithm
      of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula
      was 86.6% and 84.2%, respectively. CONCLUSION: The equation developed from the
      MDRD Study provided a more accurate estimate of GFR in our study group than
      measured creatinine clearance or other commonly used equations.

PMID- 10075614
TI  - Long-term weight patterns and risk for cholecystectomy in women.
AB  - BACKGROUND: Obesity and rapid weight loss in obese persons are known risk factors
      for gallstones. However, the effect of intentional, long-term, moderate weight
      changes on the risk for gallstones is unclear. OBJECTIVE: To study long-term
      weight patterns in a cohort of women and to examine the relation between weight
      pattern and risk for cholecystectomy. DESIGN: Prospective cohort study. SETTING:
      11 U.S. states. PARTICIPANTS: 47,153 female registered nurses who did not undergo
      cholecystectomy before 1988. MEASUREMENTS: Cholecystectomy between 1988 and 1994
      (ascertained by patient self-report). RESULTS: During the exposure period (1972
      to 1988), there was evidence of substantial variation in weight due to
      intentional weight loss during adulthood. Among cohort patients, 54.9% reported
      weight cycling with at least one episode of intentional weight loss associated
      with regain. Of the total cohort, 20.1% were light cyclers (5 to 9 lb of weight
      loss and gain), 18.8% were moderate cyclers (10 to 19 lb of weight loss and
      gain), and 16.0% were severe cyclers (> or = 20 lb of weight loss and gain). Net
      weight gain without cycling occurred in 29.3% of women; net weight loss without
      cycling was the least common pattern (4.6%). Only 11.1% of the cohort maintained
      weight within 5 lb over the 16-year period. In the study, 1751 women had
      undergone cholecystectomy between 1988 and 1994. Compared with weight
      maintainers, the relative risk for cholecystectomy (adjusted for body mass index,
      age, alcohol intake, fat intake, and smoking) was 1.20 (95% CI, 0.96 to 1.50)
      among light cyclers, 1.31 among moderate cyclers (CI, 1.05 to 1.64), and 1.68
      among severe cyclers (CI, 1.34 to 2.10). CONCLUSION: Weight cycling was highly
      prevalent in this large cohort of middle-aged women. The risk for cholecystectomy
      associated with weight cycling was substantial, independent of attained relative
      body weight.

PMID- 10075615
TI  - Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.
AB  - BACKGROUND: In a phase II study, etanercept (recombinant human tumor necrosis
      factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent
      improvement in rheumatoid arthritis over 3 months. OBJECTIVE: To confirm the
      benefit of etanercept therapy of longer duration and simplified dosing in
      patients with rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo
      controlled trial with blinded joint assessors. SETTING: 13 North American
      centers. PATIENTS: 234 patients with active rheumatoid arthritis who had an
      inadequate response to disease-modifying antirheumatic drugs. INTERVENTION: Twice
      weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6
      months. MEASUREMENTS: The primary end points were 20% and 50% improvement in
      disease activity according to American College of Rheumatology (ACR) responses at
      3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and
      other measures of disease activity at 3 and 6 months. RESULTS: Etanercept
      significantly reduced disease activity in a dose-related fashion. At 3 months,
      62% of the patients receiving 25 mg of etanercept and 23% of the placebo
      recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg
      group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40%
      and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean
      percentage reduction in the number of tender and swollen joints at 6 months was
      56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05).
      Significantly more etanercept recipients achieved a 70% ACR response, minimal
      disease status (0 to 5 affected joints), and improved quality of life. Etanercept
      was well tolerated, with no dose-limiting toxic effects. CONCLUSIONS: Etanercept
      can safely provide rapid, significant, and sustained benefit in patients with
      active rheumatoid arthritis.

PMID- 10075616
TI  - Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A
      randomized, controlled trial. Montelukast/Beclomethasone Study Group.
AB  - BACKGROUND: Oral leukotriene receptor antagonists have been shown to have
      efficacy in chronic asthma. OBJECTIVE: To compare the clinical benefit of
      montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and
      inhaled beclomethasone. DESIGN: Randomized, double-blind, double-dummy, placebo
      controlled, parallel-group, 12-week study. SETTING: 36 sites worldwide. PATIENTS:
      895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of
      predicted. INTERVENTIONS: Montelukast, 10 mg once daily at bedtime; inhaled
      beclomethasone, 200 microg twice daily, administered with a spacer device; or
      placebo. MEASUREMENTS: Primary end points were daytime asthma symptom score and
      FEV1. Secondary end points were peak expiratory flow rates in the morning and
      evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific
      quality of life, and worsening asthma episodes. RESULTS: Over the 12-week
      treatment period, the average percentage change from baseline in FEV1 was 13.1%
      with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for
      each active treatment compared with placebo; P < 0.01 for beclomethasone compared
      with montelukast). The average change from baseline in daytime symptom score was 
      0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001
      for each active treatment compared with placebo; P < 0.01 for beclomethasone
      compared with montelukast). Each agent improved peak expiratory flow rates and
      quality of life, reduced nocturnal awakenings and asthma attacks, increased the
      number of asthma-control days, and decreased the number of days with asthma
      exacerbations (P < 0.001 for each active treatment compared with placebo for each
      end point; P < 0.01 for beclomethasone compared with montelukast for each end
      point). Although beclomethasone had a greater mean clinical benefit than
      montelukast, montelukast had a faster onset of action and a greater initial
      effect. The two agents caused similar decreases in peripheral blood eosinophil
      counts (P < 0.05 for each agent compared with placebo). Both agents had
      tolerability profiles similar to that of placebo over the 12-week study.
      CONCLUSIONS: Although beclomethasone had a larger mean effect than montelukast,
      both drugs provided clinical benefit to patients with chronic asthma. This
      finding is consistent with the use of these agents as controller medications for
      chronic asthma.

PMID- 10075617
TI  - Cost-utility of three approaches to the diagnosis of sleep apnea:
      polysomnography, home testing, and empirical therapy.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with
      overnight polysomnography in a sleep laboratory. Home sleep studies can be
      performed at lower cost, but results are somewhat less reliable. Bedside
      diagnosis of OSAS without any testing has also been discussed. OBJECTIVE: To
      model the costs and utility of laboratory polysomnography, home study, and no
      testing during the 5 years after initial evaluation for OSAS. DESIGN: Cost
      utility analysis. DATA SOURCES: Published data. TARGET POPULATION: Hypothetical
      cohort of persons suspected of having OSAS. TIME HORIZON: The 5 years after
      initial evaluation for OSAS. PERSPECTIVE: Societal. INTERVENTION: Nasal
      continuous positive airway pressure when OSAS was diagnosed. MEASUREMENTS:
      Quality of life, survival and charges (as proxies for costs) for each diagnostic
      method. RESULTS OF BASE-CASE ANALYSIS: Under almost all modeled conditions,
      polysomnography provided maximal quality-adjusted life-years in the 5 years after
      the initial diagnostic evaluation. The incremental charges for polysomnography
      over home study or no testing were about $13,400 and $9200, respectively, per
      quality-adjusted life-year gained during this period. RESULTS OF SENSITIVITY
      ANALYSIS: Results were sensitive to the utility of treatment in the absence of
      OSAS. CONCLUSIONS: The cost-utility of polysomnography instead of home study or
      no testing in the diagnosis of OSAS compares favorably with that of other
      procedures for which society judges the added utility per dollar spent to be
      worthwhile. More precise determination of certain key variables in this model
      should be a goal of future research.

PMID- 10075618
TI  - Pulmonary hypertension after splenectomy?
AB  - BACKGROUND: A high prevalence of asplenia has been observed in patients with
      unexplained pulmonary hypertension. OBJECTIVE: To describe the clinical and
      histopathologic characteristics of patients with postsplenectomy pulmonary
      hypertension and to compare the prevalence of surgical asplenia in patients with
      idiopathic pulmonary hypertension and patients with other pulmonary diseases.
      DESIGN: Case series and case-control study. SETTING: University hospital in
      Hannover, Germany. PATIENTS: 61 patients with pulmonary hypertension and 151 lung
      transplant recipients. RESULTS: The prevalence of asplenia in patients with
      pulmonary hypertension was 11.5% (95% CI, 4.7% to 22.2%) compared with 0% (CI, 0%
      to 3.2%) in those without pulmonary hypertension (P < 0.001). Histopathologic
      examination of lung specimens from patients with postsplenectomy pulmonary
      hypertension showed intimal fibrosis, plexiform lesions, and abundant thrombotic
      lesions. CONCLUSION: Patients who have had splenectomy may be at increased risk
      for developing pulmonary hypertension.

PMID- 10075619
TI  - Phase I studies of hypericin, the active compound in St. John's Wort, as an
      antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols
      150 and 258.
AB  - BACKGROUND: Hypericin, the active compound in St. John's Wort, has antiretroviral
      activity in vitro. Many HIV-infected persons use St. John's wort. OBJECTIVE: To
      evaluate the safety and antiretroviral activity of hypericin in HIV-infected
      patients. DESIGN: Phase I study. SETTING: Four clinical research units. PATIENTS:
      30 HIV-infected patients with CD4 counts less than 350 cells/mm3. INTERVENTION:
      Intravenous hypericin, 0.25 or 0.5 mg/kg of body weight twice weekly or 0.25
      mg/kg three times weekly, or oral hypericin, 0.5 mg/kg daily. MEASUREMENTS:
      Safety was assessed at weekly visits. Antiretroviral activity was assessed by
      changes in HIV p24 antigen level, HIV titer, HIV RNA copies, and CD4 cell counts.
      RESULTS: Of the 30 patients who were enrolled, 16 discontinued treatment early
      because of toxic effects. Severe cutaneous phototoxicity was observed in 11 of 23
      (48% [95% CI, 27% to 69%]) evaluable patients, and dose escalation could not be
      completed. Virologic markers and CD4 cell count did not significantly change.
      CONCLUSIONS: Hypericin caused significant phototoxicity and had no antiretroviral
      activity in the limited number of patients studied.

PMID- 10075620
TI  - Assessing the generalizability of prognostic information.
AB  - Physicians are often asked to make prognostic assessments but often worry that
      their assessments will prove inaccurate. Prognostic systems were developed to
      enhance the accuracy of such assessments. This paper describes an approach for
      evaluating prognostic systems based on the accuracy (calibration and
      discrimination) and generalizability (reproducibility and transportability) of
      the system's predictions. Reproducibility is the ability to produce accurate
      predictions among patients not included in the development of the system but from
      the same population. Transportability is the ability to produce accurate
      predictions among patients drawn from a different but plausibly related
      population. On the basis of the observation that the generalizability of a
      prognostic system is commonly limited to a single historical period, geographic
      location, methodologic approach, disease spectrum, or follow-up interval, we
      describe a working hierarchy of the cumulative generalizability of prognostic
      systems. This approach is illustrated in a structured review of the Dukes and
      Jass staging systems for colon and rectal cancer and applied to a young man with
      colon cancer. Because it treats the development of the system as a "black box"
      and evaluates only the performance of the predictions, the approach can be
      applied to any system that generates predicted probabilities. Although the Dukes
      and Jass staging systems are discrete, the approach can also be applied to
      systems that generate continuous predictions and, with some modification, to
      systems that predict over multiple time periods. Like any scientific hypothesis,
      the generalizability of a prognostic system is established by being tested and
      being found accurate across increasingly diverse settings. The more numerous and
      diverse the settings in which the system is tested and found accurate, the more
      likely it will generalize to an untested setting.

PMID- 10075621
TI  - Barriers to office-based screening sigmoidoscopy: does reimbursement cover costs?
AB  - Screening with flexible sigmoidoscopy may reduce mortality rates from colorectal
      cancer. Primary care physicians are able to provide this screening procedure, but
      many have been reluctant to do so, partly because of the impression that
      reimbursement rates are inadequate to cover physician costs. This study examines
      the cost of performing flexible sigmoidoscopy in a primary care practice and
      compares this cost with the new Medicare reimbursement rate for flexible
      sigmoidoscopy. Fixed and variable costs associated with the performance of office
      based flexible sigmoidoscopy were derived from the published literature. The
      principal assumption in the analyses is that the time required to perform
      flexible sigmoidoscopy represents an opportunity cost because the physician could
      use that time to see additional patients during routine office hours. Sensitivity
      analyses were done across a range of estimates for the cost variables. When
      Medicare reimbursement rates were used, the physician's total cost for flexible
      sigmoidoscopy without biopsy was $86.86, which is similar to the Medicare
      reimbursement rate for screening flexible sigmoidoscopy (code 45330, $87.84). The
      calculations were most sensitive to estimates of equipment cost, procedure time,
      number of procedures performed per year, additional malpractice coverage, and
      revenue generated per hour of outpatient care. The estimated cost per procedure
      in a screening program that includes the ability to perform biopsy is $152.93,
      which exceeds Medicare reimbursement rates across the range of all variables
      included in the sensitivity analyses. Thus, low reimbursement may limit the
      adoption of screening flexible sigmoidoscopy with or without biopsy in primary
      care practices.

PMID- 10075622
TI  - Newer asthma therapies.

PMID- 10075623
TI  - Economic implications of the diagnosis of obstructive sleep apnea.

PMID- 10075624
TI  - Primaquine prophylaxis against malaria.

PMID- 10075625
TI  - Primaquine prophylaxis against malaria.

PMID- 10075626
TI  - Myocardial infarction associated with buprenorphine.

PMID- 10075627
TI  - Lipoprotein(a) in acromegaly.

PMID- 10075628
TI  - Low rate of venous thromboembolism in asymptomatic relatives of probands with
      factor V Leiden mutation.

PMID- 10075629
TI  - Oregon's Death with Dignity Act: ten months later.

PMID- 10075630
TI  - Controlling disease transmission in injection drug users.

PMID- 10075631
TI  - Proceedings of the 14th Enzyme Engineering Conference. Beijing, China, October 12
      17, 1997.

PMID- 10075632
TI  - Multiple intensified performance of an enzyme-catalyzed reaction in organic
      medium.
AB  - A lipase-catalyzed glycerolysis reaction (a transesterification between
      polyunsaturated fatty acid ethyl ester [PUFA] and glycerol) was investigated. Its
      performance was multiply intensified by (1) using a lipase having high specific
      activity, high activity in organic solvent, and high tolerance in organic
      solvent; (2) immobilization on fine CaCO3 powder (cheap and safe material, easy
      physical adsorption method of immobilization, reusable); (3) reaction in vacuo
      resulting in 100% conversion and effective avoidance of oxidative deterioration
      of PUFA; (4) high volumetric productivity because of no use of solvent; and (5)
      no need of further separation and purification of the oil product. It is
      emphasized that performance of biocatalytic reactions in organic media should be
      enhanced manifold for industrial implementation.

PMID- 10075633
TI  - Coenzyme-dependent oxidoreductions in organic media.

PMID- 10075634
TI  - Effect of chemical modification of cyclodextrin glycosyltransferase (CGTase) from
      Thermoanaerobacter sp. on its activity and product selectivity.

PMID- 10075635
TI  - Intrinsic alpha-chymotrypsin activity determination in acetonitrile containing
      small amounts of aqueous buffer.

PMID- 10075636
TI  - High selectivity of reactions in ice.

PMID- 10075637
TI  - Purification and characterization of the mutant enzyme W117Y of the
      dichloromethane dehalogenase from Methylophilus sp. strain DM11.

PMID- 10075638
TI  - Extracellular proteinases from extremophiles.

PMID- 10075639
TI  - Neural networks as "software sensors" in enzyme engineering.
AB  - Industrial applications of enzyme technology are rapidly increasing. On-line
      control of enzyme production processes, however, is difficult owing to the
      uncertainties typical of biological systems and to the lack of suitable on-line
      sensors for key process variables and quality attributes. We demonstrate that
      well-trained feedforward backpropagation neural networks with one hidden layer
      can be employed to overcome such problems with no need for a priori knowledge of
      the relationships of the process variables involved. Neural network programs were
      written in Microsoft Visual C++ for Windows and implemented in a personal
      computer. The goodness of fit of the trained neural network to the reference data
      was determined by the coefficient of determination, R2. Case studies of beta
      galactosidase, glucoamylase, lipase, and xylanase production processes will be
      used as examples.

PMID- 10075640
TI  - Novel double bond-transferring hydroxylation reaction involved in microbial
      metabolism of eugenol.
AB  - We isolated a eugenol-degrading bacterium, Pseudomonas fluorescens E118. This
      strain produced a novel enzyme, eugenol dehydrogenase, which catalyzes the
      conversion of eugenol into coniferyl alcohol. The enzyme was purified from the
      eugenol-induced cells of P. fluorescens E118. The purified enzyme appeared to be
      homogeneous, judging from the analysis of polyacrylamide gel electrophoresis. The
      enzyme was a 68-kDa protein composed of two different subunits (alpha subunit, 10
      kDa; and beta subunit, 58 kDa). The enzyme exhibited a cytochrome c-like
      absorption spectrum. The alpha subunit corresponded to cytochrome c. The enzyme
      catalyzed the dehydrogenation of 4-alkylphenol into the corresponding alkyl 1-(4
      hydroxyphenyl)-alcohol derivatives. The reaction products were isolated and
      identified physicochemically. The enzyme catalyzed the enantioselective
      hydroxylation of p-alkylphenols. p-Ethylphenol and p-propylphenol were converted
      to S-(-)-p-(1-hydroxyphenyl)ethanol and S-(-)-p(1-hydroxyphenyl)propanol,
      respectively.

PMID- 10075641
TI  - Paracetamol for fever in children: high time for systematic reviews of the
      evidence.

PMID- 10075642
TI  - Structure, mechanism, and regulation of mammalian adenylyl cyclase.

PMID- 10075643
TI  - Receptor-mediated targeting of fluorescent probes in living cells.
AB  - A strategy was developed to label specified sites in living cells with a wide
      selection of fluorescent or other probes and applied to study pH regulation in
      Golgi. cDNA transfection was used to target a single-chain antibody to a
      specified site such as an organelle lumen. The targeted antibody functioned as a
      high affinity receptor to trap cell-permeable hapten-fluorophore conjugates.
      Synthesized conjugates of a hapten (4-ethoxymethylene-2-phenyl-2-oxazolin-5-one,
      phOx) and fluorescent probes (Bodipy Fl, tetramethylrhodamine, fluorescein) were
      bound with high affinity (approximately 5 nM) and specific localization to the
      single-chain antibody expressed in the endoplasmic reticulum, Golgi, and plasma
      membrane of living Chinese hamster ovary cells. Using the pH-sensitive phOx
      fluorescein conjugate and ratio imaging microscopy, pH was measured in the lumen
      of Golgi (pH 6.25 +/- 0.06). Measurements of pH-dependent vacuolar H+/ATPase pump
      activity and H+ leak in Golgi provided direct evidence that resting Golgi pH is
      determined by balanced leak-pump kinetics rather than the inability of the
      H+/ATPase to pump against an electrochemical gradient. Like expression of the
      green fluorescent protein, the receptor-mediated fluorophore targeting approach
      permits specific intracellular fluorescence labeling. A significant advantage of
      the new approach is the ability to target chemical probes with custom-designed
      spectral and indicator properties.

PMID- 10075644
TI  - Identification of a GABAB receptor subunit, gb2, required for functional GABAB
      receptor activity.
AB  - G protein-coupled receptors are commonly thought to bind their cognate ligands
      and elicit functional responses primarily as monomeric receptors. In studying the
      recombinant gamma-aminobutyric acid, type B (GABAB) receptor (gb1a) and a GABAB
      like orphan receptor (gb2), we observed that both receptors are functionally
      inactive when expressed individually in multiple heterologous systems.
      Characterization of the tissue distribution of each of the receptors by in situ
      hybridization histochemistry in rat brain revealed co-localization of gb1 and gb2
      transcripts in many brain regions, suggesting the hypothesis that gb1 and gb2 may
      interact in vivo. In three established functional systems (inwardly rectifying K+
      channel currents in Xenopus oocytes, melanophore pigment aggregation, and direct
      cAMP measurements in HEK-293 cells), GABA mediated a functional response in cells
      coexpressing gb1a and gb2 but not in cells expressing either receptor
      individually. This GABA activity could be blocked with the GABAB receptor
      antagonist CGP71872. In COS-7 cells coexpressing gb1a and gb2 receptors, co
      immunoprecipitation of gb1a and gb2 receptors was demonstrated, indicating that
      gb1a and gb2 act as subunits in the formation of a functional GABAB receptor.

PMID- 10075645
TI  - Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin
      1 signaling mediators in cultured human dermal endothelial cells and mononuclear
      phagocytes.
AB  - Bacterial lipopolysaccharide (LPS)-mediated immune responses, including
      activation of monocytes, macrophages, and endothelial cells, play an important
      role in the pathogenesis of Gram-negative bacteria-induced sepsis syndrome.
      Activation of NF-kappaB is thought to be required for cytokine release from LPS
      responsive cells, a critical step for endotoxic effects. Here we investigated the
      role and involvement of interleukin-1 (IL-1) and tumor necrosis factor (TNF
      alpha) signal transducer molecules in LPS signaling in human dermal microvessel
      endothelial cells (HDMEC) and THP-1 monocytic cells. LPS stimulation of HDMEC and
      THP-1 cells initiated an IL-1 receptor-like NF-kappaB signaling cascade. In
      transient cotransfection experiments, dominant negative mutants of the IL-1
      signaling pathway, including MyD88, IRAK, IRAK2, and TRAF6 inhibited both IL-1-
      and LPS-induced NF-kappaB-luciferase activity. LPS-induced NF-kappaB activation
      was not inhibited by a dominant negative mutant of TRAF2 that is involved in TNF
      signaling. LPS-induced activation of NF-kappaB-responsive reporter gene was not
      inhibited by IL-1 receptor antagonist. TLR2 and TLR4 were expressed on the cell
      surface of HDMEC and THP-1 cells. These findings suggest that a signal
      transduction molecule in the LPS receptor complex may belong to the IL-1
      receptor/toll-like receptor (TLR) super family, and the LPS signaling cascade
      uses an analogous molecular framework for signaling as IL-1 in mononuclear
      phagocytes and endothelial cells.

PMID- 10075646
TI  - The biological and pathological function of the presenilin-1 Deltaexon 9 mutation
      is independent of its defect to undergo proteolytic processing.
AB  - The two homologous presenilins are key factors for the generation of amyloid beta
      peptide (Abeta), since Alzheimer's disease (AD)-associated mutations enhance the
      production of the pathologically relevant 42-amino acid Abeta (Abeta42), and a
      gene knockout of presenilin-1 (PS1) significantly inhibits total Abeta
      production. Presenilins undergo proteolytic processing within the domain encoded
      by exon 9, a process that may be closely related to their biological and
      pathological activity. An AD-associated mutation within the PS1 gene deletes exon
      9 (PS1Deltaexon9) due to a splicing error and results in the accumulation of the
      uncleaved full-length protein. We now demonstrate the unexpected finding that the
      pathological activity of PS1Deltaexon9 is independent of its lack to undergo
      proteolytic processing, but is rather due to a point mutation (S290C) occurring
      at the aberrant exon 8/10 splice junction. Mutagenizing the cysteine residue at
      position 290 to the original serine residue completely inhibits the pathological
      activity in regard to the elevated production of Abeta42. Like PS1Deltaexon9, the
      resulting presenilin variant (PS1Deltaexon9 C290S) accumulates as an uncleaved
      protein and fully replaces endogenous presenilin fragments. Moreover,
      PS1Deltaexon9 C290S exhibits a significantly increased biological activity in a
      highly sensitive in vivo assay as compared with the AD-associated mutation.
      Therefore not only the increased Abeta42 production but also the decreased
      biological function of PS1Deltaexon9 is due to a point mutation and independent
      of the lack of proteolytic processing.

PMID- 10075647
TI  - Mutant and wild type human alpha-synucleins assemble into elongated filaments
      with distinct morphologies in vitro.
AB  - alpha-Synuclein is a soluble presynaptic protein which is pathologically
      redistributed within intracellular lesions characteristic of several
      neurodegenerative diseases. Here we demonstrate that wild type and two mutant
      forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro
      and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with
      distinct morphologies under defined in vitro conditions. Immunogold labeling
      demonstrates that the central region of all these filaments are more robustly
      labeled than the N-terminal or C-terminal regions, suggesting that the latter
      regions are buried within the filaments. Since in vitro generated alpha-synuclein
      filaments resemble the major ultrastructural elements of authentic Lewy bodies
      that are hallmark lesions of Parkinson's disease, we propose that self
      aggregating alpha-synuclein is the major subunit protein of these filamentous
      lesions.

PMID- 10075648
TI  - The B subunit of the CAAT-binding factor NFY binds the central segment of the Co
      activator p300.
AB  - We report that the heterotrimeric transcription factor NFY or "CAAT-binding
      factor" binds the -60 region of the human H ferritin promoter, the B site. DNA
      binding analysis with specific antibodies demonstrates that NFY/B/C subunits
      tightly bind this site and that NFY/C subunit is masked in vivo by binding with
      other protein(s). NFY binds the co-activator p300. Specifically, the NFY/B
      subunit interacts with the central segment of p300 in vivo and in vitro. cAMP
      substantially increases the formation of the NFY.p300 complex. Taken together
      these data provide a general model of cAMP induction of non-CRE-containing
      promoters and suggest that the NFY-B.p300 complex is located at the 5' end of the
      promoter and the NFY-B.C. TFIIB on the 3' end toward the transcription start
      site.

PMID- 10075649
TI  - A single conductance pore for chloride ions formed by two cystic fibrosis
      transmembrane conductance regulator molecules.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      dependent protein kinase (PKA)- and ATP-regulated chloride channel, whose gating
      process involves intra- or intermolecular interactions among the cytosolic
      domains of the CFTR protein. Tandem linkage of two CFTR molecules produces a
      functional chloride channel with properties that are similar to those of the
      native CFTR channel, including trafficking to the plasma membrane, ATP- and PKA
      dependent gating, and a unitary conductance of 8 picosiemens (pS). A heterodimer,
      consisting of a wild type and a mutant CFTR, also forms an 8-pS chloride channel
      with mixed gating properties of the wild type and mutant CFTR channels. The data
      suggest that two CFTR molecules interact together to form a single conductance
      pore for chloride ions.

PMID- 10075650
TI  - Ruminant placental lactogens act as antagonists to homologous growth hormone
      receptors and as agonists to human or rabbit growth hormone receptors.
AB  - Growth hormone receptor (GHR)-mediated activity of ruminant placental lactogens
      (PLs) and ovine (o) GH was compared, using cells transfected with full size human
      (h), rabbit (rb), and oGHRs. All three PLs acted as agonists in heterologous
      bioassays, whereas in homologous bioassays in cells transfected with oGHRs they
      antagonized the oGH activity. Despite these differences, oGH and PLs bound with
      similar affinity to the oGHR extracellular domain (oGHR-ECD), indicating that the
      binding occurs through hormone site I. Gel filtration of complexes between oPL
      and oGHR-ECD showed a 1:1 stoichiometry, confirming this conclusion. The oPL
      T185D and bPL T188D, which exhibited weak biological activity mediated through
      GHRs, behaved as site I antagonists, whereas oPL G130R and bPL G133R formed a 1:1
      complex with GHR-ECDs and bound to h/rb/oGHR-ECDs with affinity similar to that
      of wild-type oPL. They had no agonistic activity in all models transfected with
      h/rb and oGHRs, but were antagonistic to all of them. In conclusion, ruminant PLs
      antagonize the activity of oGH in homologous systems, because they cannot
      homodimerize oGHRs, whereas in heterologous systems they act as agonists. The
      structural analysis hints that minor differences in the sequence of the GHR-ECDs
      may account for this difference. Since the initial step in the activity
      transduced through cytokine/hemapoietic receptors family is receptor
      homodimerization or heterodimerization, we suggest that the question of
      homologous versus heterologous interactions should be reexamined.

PMID- 10075651
TI  - Expression of the transcriptional repressor protein Kid-1 leads to the
      disintegration of the nucleolus.
AB  - The rat Kid-1 gene codes for a 66-kDa protein with KRAB domains at the NH2
      terminus and two Cys2His2-zinc finger clusters of four and nine zinc fingers at
      the COOH terminus. It was the first KRAB-zinc finger protein for which a
      transcriptional repressor activity was demonstrated. Subsequently, the KRAB-A
      domain was identified as a widespread transcriptional repressor motif. We now
      present a biochemical and functional analysis of the Kid-1 protein in transfected
      cells. The full-length Kid-1 protein is targeted to the nucleolus and adheres
      tightly to as yet undefined nucleolar structures, leading eventually to the
      disintegration of the nucleolus. The tight adherence and nucleolar distribution
      can be attributed to the larger zinc finger cluster, whereas the KRAB-A domain is
      responsible for the nucleolar fragmentation. Upon disintegration of the
      nucleolus, the nucleolar transcription factor upstream binding factor disappears
      from the nucleolar fragments. In the absence of Kid-1, the KRIP-1 protein, which
      represents the natural interacting partner of zinc finger proteins with a KRAB-A
      domain, is homogeneously distributed in the nucleus, whereas coexpression of Kid
      1 leads to a shift of KRIP-1 into the nucleolus. Nucleolar run-ons demonstrate
      that rDNA transcription is shut off in the nucleolar fragments. Our data
      demonstrate the functional diversity of the KRAB and zinc finger domains of Kid-1
      and provide new functional insights into the regulation of the nucleolar
      structure.

PMID- 10075652
TI  - Co-reconstitution of phospholamban mutants with the Ca-ATPase reveals dependence
      of inhibitory function on phospholamban structure.
AB  - Phospholamban (PLB), a 52-amino acid integral membrane protein, regulates the Ca
      ATPase (calcium pump) in cardiac sarcoplasmic reticulum through PLB
      phosphorylation mediated by beta-adrenergic stimulation. Based on site-directed
      mutagenesis and coexpression with Ca-ATPase (SERCA2a) in Sf21 insect cells or in
      HEK 293 cells, and on spin label detection of PLB oligomeric state in lipid
      bilayers, it has been proposed that the monomeric form of PLB is the inhibitory
      species, and depolymerization of PLB is essential for its regulatory function.
      Here we have studied the relationship between PLB oligomeric state and function
      by in vitro co-reconstitution of PLB and its mutants with purified Ca-ATPase. We
      compared wild type-PLB (wt-PLB), which is primarily a pentamer on SDS
      polyacrylamide gel electrophoresis (PAGE) at 25 degrees C, with two of its
      mutants, C41L-PLB and L37A-PLB, that are primarily tetramer and monomer,
      respectively. We found that the monomeric mutant L37A-PLB is a more potent
      inhibitor than wt-PLB, supporting the previous proposal that PLB monomer is the
      inhibitory species. On the other hand, C41L-PLB, which has a monomeric fraction
      comparable to that of wt-PLB on SDS-PAGE at 25 degrees C, has no inhibitory
      activity when assayed at 25 degrees C. However, at 37 degrees C, a 3-fold
      increase in the monomeric fraction of C41L-PLB on SDS-PAGE resulted in inhibitory
      activity comparable to that of wt-PLB. Upon increasing the temperature from 25 to
      37 degrees C, no change in fraction monomer or inhibitory activity for wt-PLB and
      L37A-PLB was observed. Based on these results, the extent of inhibition of Ca
      ATPase by PLB or its mutants appears to depend not only on the propensity of PLB
      to dissociate into monomers but also on the relative potency of the particular
      PLB monomer when interacting with the Ca-ATPase.

PMID- 10075653
TI  - Structure and anticoagulant activity of sulfated fucans. Comparison between the
      regular, repetitive, and linear fucans from echinoderms with the more
      heterogeneous and branched polymers from brown algae.
AB  - Sulfated fucans are among the most widely studied of all the sulfated
      polysaccharides of non-mammalian origin that exhibit biological activities in
      mammalian systems. Examples of these polysaccharides extracted from echinoderms
      have simple structures, composed of oligosaccharide repeating units within which
      the residues differ by specific patterns of sulfation among different species. In
      contrast the algal fucans may have some regular repeating structure but are
      clearly more heterogeneous when compared with the echinoderm fucans. The
      structures of the sulfated fucans from brown algae also vary from species to
      species. We compared the anticoagulant activity of the regular and repetitive
      fucans from echinoderms with that of the more heterogeneous fucans from three
      species of brown algae. Our results indicate that different structural features
      determine not only the anticoagulant potency of the sulfated fucans but also the
      mechanism by which they exert this activity. Thus, the branched fucans from brown
      algae are direct inhibitors of thrombin, whereas the linear fucans from
      echinoderms require the presence of antithrombin or heparin cofactor II for
      inhibition of thrombin, as reported for mammalian glycosaminoglycans. The linear
      sulfated fucans from echinoderms have an anticoagulant action resembling that of
      mammalian dermatan sulfate and a modest action through antithrombin. A single
      difference of one sulfate ester per tetrasaccharide repeating unit modifies the
      anticoagulant activity of the polysaccharide markedly. Possibly the spatial
      arrangements of sulfate esters in the repeating tetrasaccharide unit of the
      echinoderm fucan mimics the site in dermatan sulfate with high affinity for
      heparin cofactor II.

PMID- 10075654
TI  - Sequence dependence of the folding of collagen-like peptides. Single amino acids
      affect the rate of triple-helix nucleation.
AB  - The refolding of thermally denatured model collagen-like peptides was studied for
      a set of 21 guest triplets embedded in a common host framework: acetyl-(Gly-Pro
      Hyp)3-Gly-Xaa-Yaa-(Gly-Pro-Hyp)4-Gly-Gly-amide. The results show a strong
      dependence of the folding rate on the identity of the guest Gly-Xaa-Yaa triplet,
      with the half-times for refolding varying from 6 to 110 min (concentration = 1
      mg/ml). All triplets of the form Gly-Xaa-Hyp promoted rapid folding, with the
      rate only marginally dependent on the residue in the Xaa position. In contrast,
      triplets of the form Gly-Pro-Yaa and Gly-Xaa-Yaa were slower and showed a wide
      range of half-times, varying with the identity of the residues in the triplet. At
      low concentrations, the folding can be described by third-order kinetics,
      suggesting nucleation is rate-limiting. Data on the relative nucleation ability
      of different Gly-Xaa-Yaa triplets support the favorable nature of imino acids,
      the importance of hydroxyproline, the varying effects of the same residue in the
      Xaa position versus the Yaa position, and the difficulties encountered when
      leucine or aspartic acid are in the Yaa position. Information on the relative
      propensities of different tripeptide sequences to promote nucleation of the
      triple-helix in peptides will aid in identification of nucleation sites in
      collagen sequences.

PMID- 10075655
TI  - Retinoids inhibit interleukin-12 production in macrophages through physical
      associations of retinoid X receptor and NFkappaB.
AB  - Lipopolysaccharide (LPS) increases the production of interleukin-12 (IL-12) from
      mouse macrophages via a kappaB site within the IL-12 p40 promoter. In this study,
      we found that retinoids inhibit this LPS-stimulated production of IL-12 in a dose
      dependent manner. The NFkappaB components p50 and p65 bound retinoid X receptor
      (RXR) in a ligand-independent manner in vitro, and the interaction interfaces
      involved the p50 residues 1-245, the p65 residues 194-441, and the N-terminal
      A/B/C domains of RXR. Activation of macrophages by LPS resulted in markedly
      enhanced binding activities to the kappaB site, which significantly decreased
      upon addition of retinoids, as demonstrated by the electrophoretic mobility shift
      assays. In cotransfections of CV-1 and HeLa cells, RXR also inhibited the
      NFkappaB transactivation in a ligand-dependent manner, whereas a mutant RXR
      lacking the AF2 transactivation domain, which serves as ligand-dependent binding
      sites for transcription integrators SRC-1 and p300, was without any effect. In
      addition, coexpression of increasing amounts of SRC-1 or p300 relieved the
      retinoid-mediated inhibition of the NFkappaB transactivation. From these results,
      we propose that retinoid-mediated suppression of the IL-12 production from LPS
      activated macrophages may involve both inhibition of the NFkappaB-DNA
      interactions and competitive recruitment of transcription integrators between
      NFkappaB and RXR.

PMID- 10075656
TI  - p300 interacts with the N- and C-terminal part of PPARgamma2 in a ligand
      independent and -dependent manner, respectively.
AB  - The nuclear peroxisome proliferator-activated receptor gamma (PPARgamma)
      activates the transcription of multiple genes involved in intra- and
      extracellular lipid metabolism. Several cofactors are crucial for the stimulation
      or the silencing of nuclear receptor transcriptional activities. The two
      homologous cofactors p300 and CREB-binding protein (CBP) have been shown to co
      activate the ligand-dependent transcriptional activities of several nuclear
      receptors as well as the ligand-independent transcriptional activity of the
      androgen receptor. We show here that the interaction between p300/CBP and
      PPARgamma is complex and involves multiple domains in each protein. p300/CBP not
      only bind in a ligand-dependent manner to the DEF region of PPARgamma but also
      bind directly in a ligand-independent manner to a region in the AB domain
      localized between residue 31 to 99. In transfection experiments, p300/CBP could
      thereby enhance the transcriptional activities of both the activating function
      (AF)-1 and AF-2 domains. p300/CBP displays itself at least two docking sites for
      PPARgamma located in its N terminus (between residues 1 and 113 for CBP) and in
      the middle of the protein (between residues 1099 and 1460).

PMID- 10075657
TI  - Interactions between neurogranin and calmodulin in vivo.
AB  - Neurogranin is a neural-specific, calmodulin (CaM)-binding protein that is
      phosphorylated by protein kinase C (PKC) within its IQ domain at serine 36. Since
      CaM binds to neurogranin through the IQ domain, PKC phosphorylation and CaM
      binding are mutually exclusive. Consequently, we hypothesize that neurogranin may
      function to concentrate CaM at specific sites in neurons and release free CaM in
      response to increased Ca2+ and PKC activation. However, it has not been
      established that neurogranin interacts with CaM in vivo. In this study, we
      examined this question using yeast two-hybrid methodology. We also searched for
      additional proteins that might interact with neurogranin by screening brain cDNA
      libraries. Our data illustrate that CaM binds to neurogranin in vivo and that CaM
      is the only neurogranin-interacting protein isolated from brain cDNA libraries.
      Single amino acid mutagenesis indicated that residues within the IQ domain are
      important for CaM binding to neurogranin in vivo. The Ile-33 --> Gln point mutant
      completely inhibited and Arg-38 --> Gln and Ser-36 --> Asp point mutants reduced
      neurogranin/CaM interactions. These data demonstrate that CaM is the major
      protein that interacts with neurogranin in vivo and support the hypothesis that
      phosphorylation of neurogranin at Ser-36 regulates its binding to CaM.

PMID- 10075658
TI  - New thioredoxins and glutaredoxins as electron donors of 3'
      phosphoadenylylsulfate reductase.
AB  - Reduction of inorganic sulfate to sulfite in prototrophic bacteria occurs with 3'
      phosphoadenylylsulfate (PAPS) as substrate for PAPS reductase and is the first
      step leading to reduced sulfur for cellular biosynthetic reactions. The relative
      efficiency as reductants of homogeneous highly active PAPS reductase of the newly
      identified second thioredoxin (Trx2) and glutaredoxins (Grx1, Grx2, Grx3, and a
      mutant Grx1C14S) was compared with the well known thioredoxin (Trx1) from
      Escherichia coli. Trx1, Trx2, and Grx1 supported virtually identical rates of
      sulfite formation with a Vmax ranging from 6.6 units mg-1 (Trx1) to 5.1 units mg
      1 (Grx1), whereas Grx1C14S was only marginally active, and Grx2 and Grx3 had no
      activity. The structural difference between active reductants had no effect upon
      Km PAPS (22.5 microM). Grx1 effectively replaced Trx1 with essentially identical
      Km-values: Km trx1 (13.7 microM), Km grx1 (14.9 microM), whereas the Km trx2 was
      considerably higher (34.2 microM). The results agree with previous in vivo data
      suggesting that Trx1 or Grx1 is essential for sulfate reduction but not for
      ribonucleotide reduction in E. coli.

PMID- 10075659
TI  - Conformation and self-association of human recombinant transforming growth factor
      beta3 in aqueous solutions.
AB  - The transforming growth factors-beta (TGF-beta) are important regulatory peptides
      for cell growth and differentiation with therapeutic potential for wound healing.
      Among the several TGF-beta isoforms TGF-beta3 has a particularly low solubility
      at physiological pH and easily forms aggregates. A spectroscopic structural
      analysis of TGF-beta3 in solution has thus been difficult. In this study,
      circular dichroism spectroscopy was used to determine the secondary structural
      elements of TGF-beta3. In addition, the aggregation of TGF-beta3 was investigated
      systematically as a function of pH and salt concentration using a rapid screening
      method. Sedimentation equilibrium and sedimentation velocity analysis revealed
      that TGF-beta3 exists predominantly in two major forms: (i) monomers in solution
      at low pH and (ii) large precipitating aggregates at physiological pH. Under
      acidic conditions (pH < 3.8) the protein was not aggregated. At pH approximately
      3.9, a monomer right arrow over left arrow dimer equilibrium could be detected
      that transformed into larger aggregates at pH > 4.1. Aggregation was pronounced
      in the pH range of 4.3 < pH < 9.8 with the aggregation maximum between pH 6.5 and
      8. 5. The aggregation process was accompanied by a structural change of the
      protein. The CD spectra were characterized by an isodichroic point at 209.5 nm
      indicating a two-state equilibrium between TGF-beta3 dissolved in solution and
      aggregated TGF-beta3. Aggregated TGF-beta3 showed a higher beta-sheet content and
      lower beta-turn and random coil contributions compared with monomeric TGF-beta3.
      Both the solution structure and the aggregate structure of TGF-beta3 were
      different from the crystal structure. This was in contrast to TGF-beta2, which
      showed very similar crystal and solution structures. Under alkaline conditions
      (pH > 9.8) the turbidity disappeared and a further conformational change was
      induced. The pH dependence of the TGF-beta3 conformation in solution in the range
      of 2.3 < pH < 11. 0 was reversible. Aggregation of TGF-beta3 was, furthermore,
      influenced by the presence of salt. For pH > 3.8 the addition of salt greatly
      enhanced the tendency to aggregate, even in the very basic domain. Under
      physiological conditions (pH 7.4, cNaCl = 164 mM) TGF-beta3 has almost the
      highest tendency to aggregate and will remain in solution only at nanomolar
      concentrations.

PMID- 10075660
TI  - Modulation of the remote heme site geometry of recombinant mouse neuronal nitric
      oxide synthase by the N-terminal hook region.
AB  - The role of two essential residues at the N-terminal hook region of neuronal
      nitric-oxide synthase (nNOS) in nitric-oxide synthase activity was investigated.
      Full-length mouse nNOS proteins containing single-point mutations of Thr-315 and
      Asp-314 to alanine were produced in the Escherichia coli and baculovirus-insect
      cell expression systems. The molecular properties of the mutant proteins were
      analyzed in detail by biochemical, optical, and electron paramagnetic resonance
      spectroscopic techniques and compared with those of the wild-type enzyme.
      Replacement of Asp-314 by Ala altered the geometry around the heme site and the
      substrate-binding pocket of the heme domain and abrogated the ability of nNOS to
      form catalytically active dimers. Replacement of Thr-315 by Ala reduced the
      protein stability and altered the geometry around the heme site, especially in
      the absence of bound (6R)-5,6,7, 8-tetrahydro-L-biopterin cofactor. These results
      suggest that Asp-314 and Thr-315 both play critical structural roles in
      stabilizing the heme domain and subunit interactions in mouse nNOS.

PMID- 10075661
TI  - EPR characterization of axial bond in metal center of native and cobalt
      substituted guanylate cyclase.
AB  - The nature of the metal-proximal base bond of soluble guanylate cyclase from
      bovine lung was examined by EPR spectroscopy. When the ferrous enzyme was mixed
      with NO, a new species was transiently produced and rapidly converted to a five
      coordinate ferrous NO complex. The new species exhibited the EPR signal of six
      coordinate ferrous NO complex with a feature of histidine-ligated heme. The
      histidine ligation was further examined by using the cobalt protoporphyrin IX
      substituted enzyme. The Co2+-substituted enzyme exhibited EPR signals of a broad
      g perpendicular;1 component and a g;1 component with a poorly resolved triplet of
      14N superhyperfine splittings, which was indicative of the histidine ligation.
      These EPR features were analogous to those of alpha-subunits of Co2+-hemoglobin
      in tense state, showing a tension on the iron-histidine bond of the enzyme. The
      binding of NO to the Co2+-enzyme markedly stimulated the cGMP production by
      forming the five-coordinate NO complex. We found that N3- elicited the activation
      of the ferric enzyme by yielding five-coordinate high spin N3- heme. These
      results indicated that the activation of the enzymes was initiated by NO binding
      to the metals and proceeded via breaking of the metal-histidine bonds, and
      suggested that the iron-histidine bond in the ferric enzyme heme was broken by N3
      binding.

PMID- 10075662
TI  - Activation of NF-kappaB by RANK requires tumor necrosis factor receptor
      associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a
      novel TRAF6 interaction motif.
AB  - Various members of the tumor necrosis factor (TNF) receptor superfamily activate
      nuclear factor kappaB (NF-kappaB) and the c-Jun N-terminal kinase (JNK) pathways
      through their interaction with TNF receptor-associated factors (TRAFs) and NF
      kappaB-inducing kinase (NIK). We have previously shown that the cytoplasmic
      domain of receptor activator of NF-kappaB (RANK) interacts with TRAF2, TRAF5, and
      TRAF6 and that its overexpression activates NF-kappaB and JNK pathways. Through a
      detailed mutational analysis of the cytoplasmic domain of RANK, we demonstrate
      that TRAF2 and TRAF5 bind to consensus TRAF binding motifs located in the C
      terminus at positions 565-568 and 606-611, respectively. In contrast, TRAF6
      interacts with a novel motif located between residues 340 and 358 of RANK.
      Furthermore, transfection experiments with RANK and its deletion mutants in human
      embryonic 293 cells revealed that the TRAF6-binding region (340-358), but not the
      TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF
      kappaB activation. Moreover, a kinase mutant of NIK (NIK-KM) inhibited RANK
      induced NF-kappaB activation. However, RANK-mediated JNK activation required a
      distal portion (427-603) of RANK containing the TRAF2-binding domain. Thus, our
      results indicate that RANK interacts with various TRAFs through distinct motifs
      and activates NF-kappaB via a novel TRAF6 interaction motif, which then activates
      NIK, thus leading to NF-kappaB activation, whereas RANK most likely activates JNK
      through a TRAF2-interacting region in RANK.

PMID- 10075663
TI  - Protein folding in the absence of chemical denaturants. Reversible pressure
      denaturation of the noncovalent complex formed by the association of two protein
      fragments.
AB  - Small monomeric proteins are the best models for studying protein folding, but
      they are often too stable for denaturation using pressure as the sole perturbant.
      In the present work we subject [CI-2(1-40).(41-64)], a noncovalent complex formed
      by the association of two complementary fragments of the chymotrypsin inhibitor
      2, to high pressure to investigate the folding mechanism of a model protein.
      Pressures up to 3.5 kilobar do not affect the intact protein, but it can be
      unfolded reversibly by pressure in the presence of subdenaturing concentrations
      of guanidine chloride, with free energy and molar volume changes of 2.5 kcal mol
      1 and 42.5 ml mol-1, respectively. In contrast, the complex can be reversibly
      denatured by high pressure without the addition of chemical denaturants. However,
      the process is clearly independent of the protein concentration, indicating lack
      of dissociation. We determined a change in the free energy of 1.4 kcal mol-1 and
      a molar volume change of 35 ml mol-1 for the pressure denaturation of the
      complex. A persistent quenching of the tryptophan adds further evidence for the
      presence of residual structure in the high pressure-denatured state. This state
      also appears to be compact as the small volume change indicates, compared with
      pressure denaturation of naturally occurring dimers. Based on observations of a
      number of pressure-denatured states and on characteristics of large CI-2
      fragments with a solvent accessible core but maintaining tertiary interactions,
      the structure of the pressure-denatured state of the CI-2 complex could be
      explained by an ordered molten globule-like conformation.

PMID- 10075664
TI  - Glycosaminoglycans differentially bind HARP and modulate its biological activity.
AB  - Heparin affin regulatory peptide (HARP) is a polypeptide belonging to a family of
      heparin binding growth/differentiation factors. The high affinity of HARP for
      heparin suggests that this secreted polypeptide should also bind to heparan
      sulfate proteoglycans derived from cell surface and extracellular matrix defined
      as extracellular compartments. Using Western blot analysis, we detected HARP
      bound to heparan sulfate proteoglycans in the extracellular compartments of MDA
      MB 231 and MC 3T3-E1 as well as NIH3T3 cells overexpressing HARP protein.
      Heparitinase treatment of BEL cells inhibited HARP-induced cell proliferation,
      and the biological activity of HARP in this system was restored by the addition
      of heparin. We report that heparan sulfate, dermatan sulfate, and to a lesser
      extent, chondroitin sulfate A, displaced HARP bound to the extracellular
      compartment. Binding analyses with a biosensor showed that HARP bound heparin
      with fast association and dissociation kinetics (kass = 1.6 x 10(6) M-1 s-1;
      kdiss = 0.02 s-1), yielding a Kd value of 13 nM; the interaction between HARP and
      dermatan sulfate was characterized by slower association kinetics (kass = 0.68 x
      10(6) M-1 s-1) and a lower affinity (Kd = 51 nM). Exogenous heparin, heparan
      sulfate, and dermatan sulfate potentiated the growth-stimulatory activity of
      HARP, suggesting that corresponding proteoglycans could be involved in the
      regulation of the mitogenic activity of HARP.

PMID- 10075665
TI  - Inhibition of hTAFII32-binding implicated in the transcriptional repression by
      central regions of mutant p53 proteins.
AB  - We previously identified a movable and regulable inactivation function within the
      central region (CRts247) of a temperature-sensitive p53 (p53(ts)) mutant,
      p53(N247I). Here we showed that central regions from several p53(ts) mutants
      behaved similarly, i.e. they repressed a neighboring activation domain only when
      existing in the mutant status. Using chimeric protein GAL4VP16-CRts247 as an
      example, we demonstrated that de novo protein synthesis was not required for the
      reactivation of the chimeric protein, indicating that a post-translational
      mechanism was involved in the control of CRts247 activity. The CRts247-conferred
      thermo-regulability did not work via a mechanism demanding either an alteration
      of the subcellular compartmentalization of or the inactivation of DNA-binding
      activity of the GAL4 chimera. Further, CRts247 did not function in trans,
      eliminating the possibility that the observed repression was because of the
      competition for a putative factor(s) by the mutant p53 domain. Rather, CRts247
      bestowed temperature-dependent interaction with hTAFII32 to the VP16 activation
      domain. In a parallel experiment, CRts247 also caused a large reduction in the
      affinity of hTAFII32 to the p53 activation domain at the nonpermissive
      temperature. These results strongly suggested that inhibition of hTAFII32 binding
      could be one of the mechanisms responsible for the transcriptional repression by
      mutant p53 central regions.

PMID- 10075666
TI  - Constitutive Fas ligand gene transcription in Sertoli cells is regulated by Sp1.
AB  - The transcriptional regulation of the Fas ligand (FasL) gene in Sertoli cells was
      investigated, as these cells are known to have constitutive expression of FasL
      and hence maintain an "immune privileged" environment within the testicle. Using
      the Sertoli cell line TM4, it was demonstrated that a gene segment of the 5'
      untranslated region located between -318 and -237 relative to the translation
      start site is required for constitutive FasL transcription. Deletion and mutation
      analysis demonstrate that an Sp1 rather than an NFAT or NFKB-like DNA binding
      motif present within this region is necessary and sufficient for constitutive
      FasL gene transcription. Nuclear extracts of Sertoli cells contain Sp1 and Sp3
      that specifically binds to the Sp1 motif present in the FasL gene, and
      overexpression of Sp1 but not Sp3 leads to a further increase of transcription
      from the FasL promoter-enhancer region. The data presented demonstrates that
      constitutive FasL gene transcription in Sertoli cells is regulated by Sp1. In
      addition, it is shown that basal FasL expression in Jurkat T cells is also
      controlled by Sp1 and this is in contrast to induced FasL expression, which is
      NFAT-dependent.

PMID- 10075667
TI  - Inhibition of xanthine oxidase and xanthine dehydrogenase by nitric oxide. Nitric
      oxide converts reduced xanthine-oxidizing enzymes into the desulfo-type inactive
      form.
AB  - Xanthine oxidase (XO) and xanthine dehydrogenase (XDH) were inactivated by
      incubation with nitric oxide under anaerobic conditions in the presence of
      xanthine or allopurinol. The inactivation was not pronounced in the absence of an
      electron donor, indicating that only the reduced enzyme form was inactivated by
      nitric oxide. The second-order rate constant of the reaction between reduced XO
      and nitric oxide was determined to be 14.8 +/- 1.4 M-1 s-1 at 25 degrees C. The
      inactivated enzymes lacked xanthine-dichlorophenolindophenol activity, and the
      oxypurinol-bound form of XO was partly protected from the inactivation. The
      absorption spectrum of the inactivated enzyme was not markedly different from
      that of the normal enzyme. The flavin and iron-sulfur centers of inactivated XO
      were reduced by dithionite and reoxidized readily with oxygen, and inactivated
      XDH retained electron transfer activities from NADH to electron acceptors,
      consistent with the conclusion that the flavin and iron-sulfur centers of the
      inactivated enzyme both remained intact. Inactivated XO reduced with 6
      methylpurine showed no "very rapid" spectra, indicating that the molybdopterin
      moiety was damaged. Furthermore, inactivated XO reduced by dithionite showed the
      same slow Mo(V) spectrum as that derived from the desulfo-type enzyme. On the
      other hand, inactivated XO reduced by dithionite exhibited the same signals for
      iron-sulfur centers as the normal enzyme. Inactivated XO recovered its activity
      in the presence of a sulfide-generating system. It is concluded that nitric oxide
      reacts with an essential sulfur of the reduced molybdenum center of XO and XDH to
      produce desulfo-type inactive enzymes.

PMID- 10075668
TI  - Glycosylation of asparagine-28 of recombinant staphylokinase with high-mannose
      type oligosaccharides results in a protein with highly attenuated plasminogen
      activator activity.
AB  - The properties of recombinant staphylokinase (SakSTAR) expressed in Pichia
      pastoris cells have been determined. The single consensus N-linked
      oligosaccharide linkage site in SakSTAR (at Asn28 of the mature protein) was
      occupied in approximately 50% of the expressed protein with high-mannose-type
      oligosaccharides. The majority of these glycans ranged in polymerization state
      from Man8GlcNAc2 to Man14GlcNAc2, with the predominant species being Man10GlcNAc2
      and Man11GlcNAc2. Glycosylated SakSTAR (SakSTARg) did not differ from its
      aglycosyl form in its aggregation state in solution, its thermal denaturation
      properties, its ability to form a complex with human plasmin (hPm), the
      amidolytic properties of the respective SakSTAR-hPm complexes, or its ability to
      liberate the amino-terminal decapeptide required for formation of a functional
      SakSTAR-hPm plasminogen activator complex. However, this latter complex with
      SakSTARg showed a greatly reduced ability to activate human plasminogen (hPg) as
      compared with the same complex with the aglycosyl form of SakSTAR. We conclude
      that glycosylation at Asn28 does not affect the structural properties of SakSTAR
      or its ability to participate in the formation of an active enzymatic complex
      with hPm, but it is detrimental to the ability of the SakSTAR-hPm complex to
      serve as a hPg activator. This is likely due to restricted access of hPg to the
      active site of the SakSTARg-hPm complex.

PMID- 10075669
TI  - Androgen-independent induction of prostate-specific antigen gene expression via
      cross-talk between the androgen receptor and protein kinase A signal transduction
      pathways.
AB  - Transcription of the prostate-specific antigen (PSA) gene escapes regulation by
      androgens in advanced prostate cancer. To determine the molecular mechanism(s) of
      androgen-independent regulation of the PSA gene, the possibility that the
      androgen receptor (AR) is activated in the absence of androgen by stimulation of
      protein kinase A (PKA) was investigated. Activation of PKA by forskolin resulted
      in elevated expression of the PSA gene in androgen-depleted LNCaP cells, an
      effect that was blocked by the antiandrogen, bicalutamide. Further evidence that
      induction of PSA gene expression was dependent on AR was obtained from
      experiments using PC3 cells devoid of AR. Neither PSA, PB, nor ARR3 androgen
      responsive reporters could be induced by activation of PKA in the absence of
      transfected AR. In addition, when nuclear AR from forskolin-treated LNCaP cells
      was incubated with oligonucleotides encoding an androgen response element of the
      PSA promoter and examined by electromobility shift assay, an increase in AR
      androgen response element complex formation was observed. Lastly, cotransfection
      of an expression vector for a chimeric protein encoding the amino-terminal domain
      of the human AR linked to Gal4 and a 5xGal4UAS reporter gene construct resulted
      in activation of the amino-terminal domain of the AR by stimulation of PKA
      activity. These results demonstrate androgen-independent induction of PSA gene
      expression in prostate cancer cells by an AR-dependent pathway.

PMID- 10075670
TI  - In vivo and in vitro function of the Escherichia coli periplasmic cysteine
      oxidoreductase DsbG.
AB  - We have characterized in vivo and in vitro the recently identified DsbG from
      Escherichia coli. In addition to sharing sequence homology with the thiol
      disulfide exchange protein DsbC, DsbG likewise was shown to form a stable
      periplasmic dimer, and it displays an equilibrium constant with glutathione
      comparable with DsbA and DsbC. DsbG was found to be expressed at approximately
      25% the level of DsbC. In contrast to earlier results (Andersen, C. L., Matthey
      Dupraz, A., Missiakas, D., and Raina, S. (1997) Mol. Microbiol. 26, 121-132), we
      showed that dsbG is not essential for growth and that dsbG null mutants display
      no defect in folding of multiple disulfide-containing heterologous proteins.
      Overexpression of DsbG, however, was able to restore the ability of dsbC mutants
      to express heterologous multidisulfide proteins, namely bovine pancreatic trypsin
      inhibitor, a protein with three disulfides, and to a lesser extent, mouse
      urokinase (12 disulfides). As in DsbC, the putative active site thiols in DsbG
      are completely reduced in vivo in a dsbD-dependent fashion, as would be expected
      if DsbG is acting as a disulfide isomerase or reductase. However, the latter is
      not likely because DsbG could not catalyze insulin reduction in vitro. Overall,
      our results indicate that DsbG functions primarily as a periplasmic disulfide
      isomerase with a narrower substrate specificity than DsbC.

PMID- 10075671
TI  - The STAT3-independent signaling pathway by glycoprotein 130 in hepatic cells.
AB  - Interleukin (IL)-6 is a major regulator of hepatic acute-phase plasma protein
      (APP) genes. The membrane-proximal 133-amino acid cytoplasmic domain of
      glycoprotein (gp) 130, containing one copy of the Box3 motif, is sufficient to
      transmit a productive signal to endogenous APP genes in rat hepatoma H-35 cells.
      In contrast, a mutant gp130 domain lacking the Box3 motif activates Janus kinases
      to a normal level but fails to activate signal transducer and activator of
      transcription 3 and to up-regulate a number of APP genes, including thiostatin,
      fibrinogen, hemopexin, and haptoglobin. However, in the absence of Box3, gp130
      still stimulates the expression of alpha2-macroglobulin and synergizes with IL-1
      to up-regulate alpha1-acid glycoprotein. The Box3 motif is not required for
      activation of the SH2-containing protein tyrosine phosphatase 2 or the mitogen
      activated protein kinase (MAPK), nor is the immediate induction of egr-1 and junB
      significantly altered. Surprisingly, gp130 without any functional Box3 stimulates
      prolonged activation of MAPK, leading to an extended period of up-regulation of
      egr-1 and to an extracellularly regulated kinase-mediated reduction in the IL-6
      stimulated production of thiostatin. IL-6 reduces proliferation of H-35 cells
      through signaling by the Box3. In addition, cells expressing Box3-deficient gp130
      showed distinct morphologic changes upon receptor activation. Taken together,
      these results indicate that Box3-derived and Box3-independent signals cooperate
      in the control of hepatic APP genes and that Box3 may be involved in the
      modulation of MAPK activity in gp130 signaling.

PMID- 10075672
TI  - Transcriptional repression of the cystic fibrosis transmembrane conductance
      regulator gene, mediated by CCAAT displacement protein/cut homolog, is associated
      with histone deacetylation.
AB  - Human cystic fibrosis transmembrane conductance regulator gene (CFTR)
      transcription is tightly regulated by nucleotide sequences upstream of the
      initiator sequences. Our studies of human CFTR transcription focus on identifying
      transcription factors bound to an inverted CCAAT consensus or "Y-box element."
      The human homeodomain CCAAT displacement protein/cut homolog (CDP/cut) can bind
      to the Y-box element through a cut repeat and homeobox. Analysis of stably
      transfected cell lines with wild-type and mutant human CFTR-directed reporter
      genes demonstrates that human histone acetyltransferase GCN5 and transcription
      factor ATF-1 can potentiate CFTR transcription through the Y-box element. We have
      found 1) that human CDP/cut acts as a repressor of CFTR transcription through the
      Y-box element by competing for the sites of transactivators hGCN5 and ATF-1; 2)
      that the ability of CDP/cut to repress activities of hGCN5 and ATF-1 activity is
      contingent on the amount of CDP/cut expression; 3) that histone acetylation may
      have a role in the regulation of gene transcription by altering the accessibility
      of the CFTR Y-box for sequence-specific transcription factors; 4) that
      trichostatin A, an inhibitor of histone deacetylase activity, activates
      transcription of CFTR through the Y-box element; 5) that the inhibition of
      histone deacetylase activity leads to an alteration of local chromatin structure
      requiring an intact Y-box sequence in CFTR; 6) that immunocomplexes of CDP/cut
      possess an associated histone deacetylase activity; 7) that the carboxyl region
      of CDP/cut, responsible for the transcriptional repressor function, interacts
      with the histone deacetylase, HDAC1. We propose that CFTR transcription may be
      regulated through interactions with factors directing the modification of
      chromatin and requires the conservation of the inverted CCAAT (Y-box) element of
      the CFTR promoter.

PMID- 10075673
TI  - Interaction between dietary methionine and methyl donor intake on rat liver
      betaine-homocysteine methyltransferase gene expression and organization of the
      human gene.
AB  - We previously showed that rat liver betaine-homocysteine methyltransferase (BHMT)
      mRNA content and activity increased 4-fold when rats were fed a methionine
      deficient diet containing adequate choline, compared with rats fed the same diet
      with control levels of methionine (Park, E. I., Renduchintala, M. S., and Garrow,
      T. A. (1997) J. Nutr. Biochem. 8, 541-545). A further 2-fold increase was
      observed in rats fed the methionine-deficient diet with supplemental betaine. The
      nutrition studies reported here were designed to determine whether other methyl
      donors would induce rat liver BHMT gene expression when added to a methionine
      deficient diet and to define the relationship between the degree of methionine
      restriction and level of methyl donor intake on BHMT expression. Therefore, rats
      were fed amino acid-defined diets varying in methionine and methyl donor
      composition. The effect of diet on BHMT expression was evaluated using Northern,
      Western, and enzyme activity analyses. Similar to when betaine was added to a
      methionine-deficient diet, choline or sulfonium analogs of betaine induced BHMT
      expression. The diet-induced induction of hepatic BHMT activity was mediated by
      increases in the steady-state level of its mRNA and immunodetectable protein.
      Using methyl donor-free diets, we found that methionine restriction was required
      but alone not sufficient for the high induction of BHMT expression. Concomitant
      with methionine restriction, dietary methyl groups were required for high levels
      of BHMT induction, and a dose-dependent relationship was observed between methyl
      donor intake and BHMT induction. Furthermore, the severity of methionine
      restriction influenced the magnitude of BHMT induction. To study the molecular
      mechanisms that regulate the expression of BHMT, we have cloned the human BHMT
      gene. This gene spans about 20 kilobases of DNA and contains 8 exons and 7
      introns. Using RNA isolated from human liver and hepatoma cells, a major
      transcriptional start site has been mapped using the 5' rapid amplification of
      cDNA ends technique, and this start site is 26 nucleotides downstream from a
      putative TATA box.

PMID- 10075674
TI  - Involvement of the Glu724-Pro760 region of the dihydropyridine receptor II-III
      loop in skeletal muscle-type excitation-contraction coupling.
AB  - Our previous study (El-Hayek, R., Antoniu, B., Wang, J. P., Hamilton, S. L., and
      Ikemoto, N. (1995) J. Biol. Chem. 270, 22116-22118) suggested the hypothesis that
      skeletal muscle-type excitation-contraction coupling is regulated by two domains
      (activating and blocking) of the II-III loop of the dihydropyridine receptor
      alpha1 subunit. We investigated this hypothesis by examining conformational
      changes in the ryanodine receptor induced by synthetic peptides and by transverse
      tubular system (T-tubule) depolarization. Peptide A, corresponding to the Thr671
      Leu690 region, rapidly changed the ryanodine receptor conformation from a blocked
      state (low fluorescence of the conformational probe, methyl coumarin acetamide,
      attached specifically to the ryanodine receptor) to an activated state (high
      methyl coumarin acetamide fluorescence) as T-tubule depolarization did. Peptide
      C, corresponding to the Glu724-Pro760 region, blocked both conformational changes
      induced by peptide A and T-tubule depolarization. Its ability to block peptide A
      induced and depolarization-induced activation was considerably impaired by
      replacing the portion of peptide C corresponding to the Phe725-Pro742 region of
      the loop with cardiac muscle-type sequence. These results are consistent with the
      model that depolarization-induced activation of excitation-contraction coupling
      and blocking/repriming are mediated by the peptide A region and the peptide C
      region (containing the critical Phe725-Pro742 sequence) of the II-III loop,
      respectively.

PMID- 10075675
TI  - Sec24 proteins and sorting at the endoplasmic reticulum.
AB  - COPII proteins are necessary to generate secretory vesicles at the endoplasmic
      reticulum. In yeast, the Sec24p protein is the only COPII component in which two
      close orthologues have been identified. By using gene knock-out in yeast, we
      found that the absence of one of these Sec24 orthologues resulted in a selective
      secretion defect for a subset of proteins released into the medium. Data base
      searches revealed the existence of an entire family of Sec24-related proteins in
      humans, worms, flies, and plants. We identified and cloned two new human cDNAs
      encoding proteins homologous to yeast Sec24p, in addition to two human cDNAs
      already present within the data bases. The entire Sec24 family identified to date
      is characterized by clusters of highly conserved residues within the 2/3 carboxyl
      terminal domain of all the proteins and a divergent amino terminus domain. Human
      (h) Sec24 orthologues co-immunoprecipitate with hSec23Ap and migrate as a complex
      by size exclusion chromatography. Immunofluorescence microscopy confirmed that
      these proteins co-localize with hSec23p and hSec13p. Together, our data suggest
      that in addition to its role in the shaping up of the vesicle, the Sec23-24p
      complex may be implicated in cargo selection and concentration.

PMID- 10075676
TI  - Nerve growth factor inhibits HCO3- absorption in renal thick ascending limb
      through inhibition of basolateral membrane Na+/H+ exchange.
AB  - Nerve growth factor (NGF) inhibits transepithelial HCO3- absorption in the rat
      medullary thick ascending limb (MTAL). To investigate the mechanism of this
      inhibition, MTALs were perfused in vitro in Na+-free solutions, and apical and
      basolateral membrane Na+/H+ exchange activities were determined from rates of pHi
      recovery after lumen or bath Na+ addition. NGF (0.7 nM in the bath) had no effect
      on apical Na+/H+ exchange activity, but inhibited basolateral Na+/H+ exchange
      activity by 50%. Inhibition of basolateral Na+/H+ exchange activity with
      ethylisopropyl amiloride (EIPA) secondarily reduces apical Na+/H+ exchange
      activity and HCO3- absorption in the MTAL (Good, D. W., George, T., and Watts, B.
      A., III (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 12525-12529). To determine
      whether a similar mechanism could explain inhibition of HCO3- absorption by NGF,
      apical Na+/H+ exchange activity was assessed in physiological solutions (146 mM
      Na+) by measurement of the initial rate of cell acidification after lumen EIPA
      addition. Under these conditions, in which basolateral Na+/H+ exchange activity
      is present, NGF inhibited apical Na+/H+ exchange activity. Inhibition of HCO3-
      absorption by NGF was eliminated in the presence of bath EIPA or in the absence
      of bath Na+. Also, NGF blocked inhibition of HCO3- absorption by bath EIPA. We
      conclude that NGF inhibits basolateral Na+/H+ exchange activity in the MTAL, an
      effect opposite from the stimulation of Na+/H+ exchange by growth factors in
      other systems. NGF inhibits transepithelial HCO3- absorption through inhibition
      of basolateral Na+/H+ exchange, most likely as the result of functional coupling
      in which primary inhibition of basolateral Na+/H+ exchange activity results
      secondarily in inhibition of apical Na+/H+ exchange activity. These findings
      establish a role for basolateral Na+/H+ exchange in the regulation of renal
      tubule HCO3- absorption.

PMID- 10075677
TI  - The DNA-dependent protein kinase catalytic activity regulates DNA end processing
      by means of Ku entry into DNA.
AB  - The DNA-dependent protein kinase (DNA-PK) is required for double-strand break
      repair in mammalian cells. DNA-PK contains the heterodimer Ku and a 460-kDa
      serine/threonine kinase catalytic subunit (p460). Ku binds in vitro to DNA
      termini or other discontinuities in the DNA helix and is able to enter the DNA
      molecule by an ATP-independent process. It is clear from in vitro experiments
      that Ku stimulates the recruitment to DNA of p460 and activates the kinase
      activity toward DNA-binding protein substrates in the vicinity. Here, we have
      examined in human nuclear cell extracts the influence of the kinase catalytic
      activity on Ku binding to DNA. We demonstrate that, although Ku can enter DNA
      from free ends in the absence of p460 subunit, the kinase activity is required
      for Ku translocation along the DNA helix when the whole Ku/p460 assembles on DNA
      termini. When the kinase activity is impaired, DNA-PK including Ku and p460 is
      blocked at DNA ends and prevents their processing by either DNA polymerization,
      degradation, or ligation. The control of Ku entry into DNA by DNA-PK catalytic
      activity potentially represents an important regulation of DNA transactions at
      DNA termini.

PMID- 10075678
TI  - Formation of HNK-1 determinants and the glycosaminoglycan tetrasaccharide linkage
      region by UDP-GlcUA:Galactose beta1, 3-glucuronosyltransferases.
AB  - While expression-cloning enzymes involved in heparan sulfate biosynthesis, we
      isolated a cDNA that encodes a protein 65% identical to the UDP
      GlcUA:glycoprotein beta1, 3-glucuronosyltransferase (GlcUAT-P) involved in
      forming HNK-1 carbohydrate epitopes (3OSO3GlcUAbeta1,3Gal-) on glycoproteins. The
      cDNA contains an open reading frame coding for a protein of 335 amino acids with
      a predicted type II transmembrane protein orientation. Cotransfection of the cDNA
      with HNK-1 3-O-sulfotransferase produced HNK-1 carbohydrate epitopes in Chinese
      hamster ovary (CHO) cells and COS-7 cells. In vitro, a soluble recombinant form
      of the enzyme transferred GlcUA in beta-linkage to Galbeta1,3/4GlcNAcbeta-O
      naphthalenemethanol, which resembles the core oligosaccharide on which the HNK-1
      epitope is assembled. However, the enzyme greatly preferred Galbeta1, 3Galbeta-O
      naphthalenemethanol, a disaccharide component found in the linkage region
      tetrasaccharide in chondroitin sulfate and heparan sulfate. During the course of
      this study, a human cDNA clone was described that was thought to encode UDP
      GlcUA:Galbeta1,3Gal-R glucuronosyltransferase (GlcUAT-I), involved in the
      formation of the linkage region of glycosaminoglycans (Kitagawa, H., Tone, Y.,
      Tamura, J., Neumann, K. W., Ogawa, T., Oka, S., Kawasaki, T., and Sugahara, K.
      (1998) J. Biol. Chem. 273, 6615-6618). The deduced amino acid sequences of the
      CHO and human cDNAs are 95% identical, suggesting that they are in fact
      homologues of the same gene. Transfection of a CHO cell mutant defective in
      GlcUAT-I with the hamster cDNA restored glycosaminoglycan assembly in vivo,
      confirming its identity. Interestingly, transfection of the mutant with GlcUAT-P
      also restored glycosaminoglycan synthesis. Thus, both GlcUAT-P and GlcUAT-I have
      overlapping substrate specificities. However, the expression of the two genes was
      entirely different, with GlcUAT-I expressed in all tissues tested and GlcUAT-P
      expressed only in brain. These findings suggest that, in neural tissues, GlcUAT-P
      may participate in both HNK-1 and glycosaminoglycan production.

PMID- 10075679
TI  - Roles of the transducin alpha-subunit alpha4-helix/alpha4-beta6 loop in the
      receptor and effector interactions.
AB  - The visual GTP-binding protein, transducin, couples light-activated rhodopsin
      (R*) with the effector enzyme, cGMP phosphodiesterase in vertebrate photoreceptor
      cells. The region corresponding to the alpha4-helix and alpha4-beta6 loop of the
      transducin alpha-subunit (Gtalpha) has been implicated in interactions with the
      receptor and the effector. Ala-scanning mutagenesis of the alpha4-beta6 region
      has been carried out to elucidate residues critical for the functions of
      transducin. The mutational analysis supports the role of the alpha4-beta6 loop in
      the R*-Gtalpha interface and suggests that the Gtalpha residues Arg310 and Asp311
      are involved in the interaction with R*. These residues are likely to contribute
      to the specificity of the R* recognition. Contrary to the evidence previously
      obtained with synthetic peptides of Gtalpha, our data indicate that none of the
      alpha4-beta6 residues directly or significantly participate in the interaction
      with and activation of phosphodiesterase. However, Ile299, Phe303, and Leu306
      form a network of interactions with the alpha3-helix of Gtalpha, which is
      critical for the ability of Gtalpha to undergo an activational conformational
      change. Thereby, Ile299, Phe303, and Leu306 play only an indirect role in the
      effector function of Gtalpha.

PMID- 10075680
TI  - Characterization of the inhibition of protein phosphatase-1 by DARPP-32 and
      inhibitor-2.
AB  - Phospho-DARPP-32 (where DARPP-32 is dopamine- and cAMP-regulated phosphoprotein,
      Mr 32,000), its homolog, phospho-inhibitor-1, and inhibitor-2 are potent
      inhibitors (IC50 approximately 1 nM) of the catalytic subunit of protein
      phosphatase-1 (PP1). Our previous studies have indicated that a region
      encompassing residues 6-11 (RKKIQF) and phospho-Thr-34, of phospho-DARPP-32,
      interacts with PP1. However, little is known about specific regions of inhibitor
      2 that interact with PP1. We have now characterized in detail the interaction of
      phospho-DARPP-32 and inhibitor-2 with PP1. Mutagenesis studies indicate that
      within DARPP-32 Phe-11 and Ile-9 play critical roles, with Lys-7 playing a lesser
      role in inhibition of PP1. Pro-33 and Pro-35 are also important, as is the number
      of amino acids between residues 7 and 11 and phospho-Thr-34. For inhibitor-2,
      deletion of amino acids 1-8 (I2-(9-204)) or 100-204 (I2-(1-99)) had little effect
      on the ability of the mutant proteins to inhibit PP1. Further deletion of
      residues 9-13 (I2-(14-204)) resulted in a large decrease in inhibitory potency
      (IC50 approximately 800 nM), whereas further COOH-terminal deletion (I2-(1-84))
      caused a moderate decrease in inhibitory potency (IC50 approximately 10 nM).
      Within residues 9-13 (PIKGI), mutagenesis indicated that Ile-10, Lys-11, and Ile
      13 play critical roles. The peptide I2-(6-20) antagonized the inhibition of PP-1
      by inhibitor-2 but had no effect on inhibition by phospho-DARPP-32. In contrast,
      the peptide D32-(6-38) antagonized the inhibition of PP1 by phospho-DARPP-32,
      inhibitor-2, and I2-(1-120) but not I2-(85-204). These results indicate that
      distinct amino acid motifs contained within the NH2 termini of phospho-DARPP-32
      (KKIQF, where italics indicate important residues) and inhibitor-2 (IKGI) are
      critical for inhibition of PP1. Moreover, residues 14-84 of inhibitor-2 and
      residues 6-38 of phospho-DARPP-32 share elements that are important for
      interaction with PP1.

PMID- 10075681
TI  - Activation of ryanodine receptors by imperatoxin A and a peptide segment of the
      II-III loop of the dihydropyridine receptor.
AB  - Excitation-contraction coupling in skeletal muscle is believed to be triggered by
      direct protein-protein interactions between the sarcolemmal dihydropyridine
      sensitive Ca2+ channel and the Ca2+ release channel/ryanodine receptor (RyR) of
      sarcoplasmic reticulum. A 138-amino acid cytoplasmic loop between repeats II and
      III of the alpha1 subunit of the skeletal dihydropyridine receptor (the II-III
      loop) interacts with a region of the RyR to elicit Ca2+ release. In addition,
      small segments (10-20 amino acid residues) of the II-III loop retain the capacity
      to activate Ca2+ release. Imperatoxin A, a 33-amino acid peptide from the
      scorpion Pandinus imperator, binds directly to the RyR and displays structural
      and functional homology with an activating segment of the II-III loop (Glu666
      Leu690). Mutations in a structural motif composed of a cluster of basic amino
      acids followed by Ser or Thr dramatically reduce or completely abolish the
      capacity of the peptides to activate RyRs. Thus, the Imperatoxin A-RyR
      interaction mimics critical molecular characteristics of the II-III loop-RyR
      interaction and may be a useful tool to elucidate the molecular mechanism that
      couples membrane depolarization to sarcoplasmic reticulum Ca2+ release in vivo.

PMID- 10075682
TI  - TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium
      channel family.
AB  - Potassium channels are found in all mammalian cell types, and they perform many
      distinct functions in both excitable and non-excitable cells. These functions are
      subserved by several different families of potassium channels distinguishable by
      primary sequence features as well as by physiological characteristics. Of these
      families, the tandem pore domain potassium channels are a new and distinct class,
      primarily distinguished by the presence of two pore-forming domains within a
      single polypeptide chain. We have cloned a new member of this family, TWIK-2,
      from a human brain cDNA library. Primary sequence analysis of TWIK-2 shows that
      it is most closely related to TWIK-1, especially in the pore-forming domains.
      Northern blot analysis reveals the expression of TWIK-2 in all human tissues
      assayed except skeletal muscle. Human TWIK-2 expressed heterologously in Xenopus
      oocytes is a non-inactivating weak inward rectifier with channel properties
      similar to TWIK-1. Pharmacologically, TWIK-2 channels are distinct from TWIK-1
      channels in their response to quinidine, quinine, and barium. TWIK-2 is inhibited
      by intracellular, but not extracellular, acidification. This new clone reveals
      the existence of a subfamily in the tandem pore domain potassium channel family
      with weak inward rectification properties.

PMID- 10075683
TI  - Isolation and characterization of a novel promoter for the bovine growth hormone
      receptor gene.
AB  - The use of alternative promoters represents an important mechanism for the
      regulation of growth hormone receptor (GHR) gene expression. Two promoters have
      been isolated previously for the GHR gene: the P1 promoter that drives liver
      specific expression, and the P2 promoter that drives ubiquitous expression. In
      the present study, we isolated a third GHR promoter termed P3. The P3 promoter
      was GC-rich and TATA-less. The P3 promoter was able to drive the expression of a
      luciferase reporter gene in cell lines Hep G2, PLC/PRF/5, and BHK-21. In vivo,
      the P3 promoter initiated transcription from two major sites in exon 1C of the
      GHR gene in many tissues. In the adult bovine liver, the P3-transcribed GHR mRNA
      represented only 10% of the total GHR mRNA pool. In non-hepatic tissues such as
      kidney, skeletal muscle, mammary gland, and uterus, P3-transcribed GHR mRNA
      represented 30-40% of the total GHR mRNA pool. Within the bovine GHR gene, the P3
      promoter was located immediately downstream from the P2 promoter. In transfected
      cells, the P2 promoter served as an enhancer for the P3 promoter. Existence and
      co-regulation of two ubiquitous promoters may be a mechanism for achieving a high
      level of expression of the GHR gene in multiple tissues.

PMID- 10075684
TI  - Specific binding of the E2 subunit of pyruvate dehydrogenase to the upstream
      region of Bacillus thuringiensis protoxin genes.
AB  - During sporulation, Bacillus thuringiensis produces inclusions comprised of
      different amounts of several related protoxins, each with a unique specificity
      profile for insect larvae. A major class of these genes designated cry1 have
      virtually identical dual overlapping promoters, but the upstream sequences
      differ. A gel retardation assay was used to purify a potential regulatory protein
      which bound with different affinities to these sequences in three cry1 genes. It
      was identified as the E2 subunit of pyruvate dehydrogenase. There was specific
      competition for binding by homologous gene sequences but not by pUC nor Bacillus
      subtilis DNA; calf thymus DNA competed at higher concentrations. The B.
      thuringiensis gene encoding E2 was cloned, and the purified glutathione S
      transferase-E2 fusion protein footprinted to a consensus binding sequence within
      an inverted repeat and to a potential bend region, both sites 200-300 base pairs
      upstream of the promoters. Mutations of these sites in the cry1A gene resulted in
      decreased binding of the E2 protein and altered kinetics of expression of a
      fusion of this regulatory region with the lacZ gene. Recruitment of the E2
      subunit as a transcription factor could couple the change in post exponential
      catabolism to the initiation of protoxin synthesis.

PMID- 10075685
TI  - Ecto-ATPase activity of alpha-sarcoglycan (adhalin).
AB  - alpha-Sarcoglycan is a component of the sarcoglycan complex of dystrophin
      associated proteins. Mutations of any of the sarcoglycan genes cause specific
      forms of muscular dystrophies, collectively termed sarcoglycanopathies.
      Importantly, a deficiency of any specific sarcoglycan affects the expression of
      the others. Thus, it appears that the lack of sarcoglycans deprives the muscle
      cell of an essential, yet unknown function. In the present study, we provide
      evidence for an ecto-ATPase activity of alpha-sarcoglycan. alpha-Sarcoglycan
      binds ATP in a Mg2+-dependent and Ca2+-independent manner. The binding is
      inhibited by 3'-O-(4-benzoyl)benzoyl ATP and ADP. Sequence analysis reveals the
      existence of a consensus site for nucleotide binding in the extracellular domain
      of the protein. An antibody against this sequence inhibits the binding of ATP. A
      dystrophin.dystrophin-associated protein preparation demonstrates a Mg-ATPase
      activity that is inhibited by the antibody but not by inhibitors of endo-ATPases.
      In addition, we demonstrate the presence in the sarcolemmal membrane of a P2X
      type purinergic receptor. These data suggest that alpha-sarcoglycan may modulate
      the activity of P2X receptors by buffering the extracellular ATP concentration.
      The absence of alpha-sarcoglycan in sarcoglycanopathies leaves elevated the
      concentration of extracellular ATP and the persistent activation of P2X
      receptors, leading to intracellular Ca2+ overload and muscle fiber death.

PMID- 10075686
TI  - L-764406 is a partial agonist of human peroxisome proliferator-activated receptor
      gamma. The role of Cys313 in ligand binding.
AB  - Insulin-sensitizing thiazolidinedione (TZD) compounds are high affinity ligands
      for a member of the nuclear receptor family, peroxisome proliferator-activated
      receptor (PPAR) gamma. A scintillation proximity assay for measurement of 3H
      radiolabeled TZD binding to human PPARgamma under homogeneous conditions was
      developed. Using this approach, a novel non-TZD compound (L-764406) was shown to
      be a potent (apparent binding IC50 of 70 nM) PPARgamma ligand. Preincubation of
      PPARgamma with L-764406 prevented binding of the [3H]TZD, suggesting a covalent
      interaction with the receptor; in addition, structurally related analogues of L
      764406, which would be predicted not to interact with PPARgamma in a covalent
      fashion, did not displace [3H]TZD binding to PPARgamma. Covalent binding of L
      764406 was proven by an observed molecular weight shift of a tryptic PPARgamma
      ligand binding domain (LBD) peptide by mass spectrometric analysis. A specific
      cysteine residue (Cys313 in helix 3 of hPPARgamma2) was identified as the
      attachment site for this compound. In protease protection experiments, the
      liganded receptor adopted a typical agonist conformation. L-764406 exhibited
      partial agonist activity in cells expressing a chimeric receptor containing the
      PPARgamma LBD and a cognate reporter gene and also induced the expression of the
      adipocyte-specific gene aP2 in 3T3-L1 cells. In contrast, L-764406 did not
      exhibit activity in cells transfected with chimeric receptors containing
      PPARalpha or PPARdelta LBDs. The partial agonist properties of L-764406 were also
      evident in a co-activator association assay, indicating that the increased
      transcription in cells was co-activator mediated. Thus, L-764406 is a novel non
      TZD ligand for PPARgamma and is also the first known partial agonist for this
      receptor. The results suggest a critical functional role for Cys313, and helix 3,
      in contributing to ligand binding and subsequent agonist-induced conformational
      changes.

PMID- 10075687
TI  - Volume expansion stimulates p72(syk) and p56(lyn) in skate erythrocytes.
AB  - Hypotonic volume expansion of skate erythrocytes rapidly stimulates the tyrosine
      phosphorylation of band 3, the membrane protein thought to mediate the
      osmotically sensitive taurine efflux. Skate erythrocytes possess numerous
      tyrosine kinases including p59fyn, p56lyn, pp60(src), and p72(syk), demonstrated
      by immune complex assays measuring autocatalytic kinase activity. Inclusion of
      the cytoplasmic domain of band 3 in this assay showed that only Syk and Lyn can
      directly phosphorylate the cytoplasmic domain of band 3. Upon cell volume
      expansion, Syk activity was increased as assessed by three different assays
      (immune complex assay measuring autophosphorylation, assay of the level of
      phosphotyrosine of the immunoprecipitated kinase, and assay of level of 32P in
      the kinase immunoprecipitated from cells prelabeled with 32PO4 and then volume
      expanded). The tyrosine kinase Lyn was also stimulated by volume expansion, most
      notably when analyzed by the latter two methods. Volume expansion stimulated a
      large increase in the ability of Syk to phosphorylate band 3 at times that
      coincide with the stimulation of taurine flux. The stilbene piceatannol inhibited
      Syk preferentially over Lyn and other tyrosine kinases and inhibited volume
      stimulated taurine efflux in a concentration-dependent manner similar to that for
      the inhibition of Syk. Two major phosphorylation peaks were detected in tryptic
      digests of cdb3 separated by reverse phase HPLC. Edman degradation demonstrated a
      phosphotyrosine in a YXXL motif. In conclusion, p72(syk) appears to be a strong
      candidate as a pivotal signal-transducing step in the volume-activated taurine
      efflux in skate red cells. The level of band-3 phosphorylation may be regulated,
      in addition, by a protein-tyrosine phosphatase of the 1B variety.

PMID- 10075688
TI  - A short loop on the ALK-2 and ALK-4 activin receptors regulates signaling
      specificity but cannot account for all their effects on early Xenopus
      development.
AB  - Activin, a member of the transforming growth factor beta (TGF-beta) superfamily,
      signals through a heteromeric complex of type I and type II serine-threonine
      kinase receptors. The two activin type I receptors previously identified, ALK-2
      (ActR-I) and ALK-4 (ActR-IB), have distinct effects on gene expression,
      differentiation and morphogenesis in the Xenopus animal cap assay. ALK-4
      reproduces the effects of activin treatment including the dose-dependent
      induction of progressively more dorso-anterior mesodermal and endodermal markers,
      whereas ALK-2 induces only ventral mesodermal markers and counteracts the effects
      of ALK-4. To identify regions of the receptors that determine signaling
      specificity we have generated chimeras of the constitutively active ALK-2 and ALK
      4 receptors (termed ALK-2* and ALK-4*). The effects of these chimeric receptors
      on gene expression and morphogenetic movements implicate the loop between kinase
      subdomains IV and V in mediating the strong dorsal gene-inducing properties of
      ALK-4*; when the seven amino acids comprising this loop are transferred from ALK
      4* to ALK-2*, the resulting chimeric receptor is capable of inducing the
      expression of dorsal-specific genes. In contrast, when the equivalent region of
      ALK-2* is transferred to the ALK-4* backbone it cannot effectively counteract the
      dorsalizing effects of ALK-4*, suggesting that other regions of type I receptors
      are also involved in determining signal specificity.

PMID- 10075689
TI  - Ras proteins induce senescence by altering the intracellular levels of reactive
      oxygen species.
AB  - Human diploid fibroblasts eventually lose the capacity to replicate in culture
      and enter a viable but nonproliferative state of senescence. Recently, it has
      been demonstrated that retroviral-mediated gene transfer into primary fibroblasts
      of an activated ras gene (V12ras) rapidly accelerates development of the
      senescent phenotype. Using this in vitro system, we have sought to define the
      mediators of Ras-induced senescence. We demonstrate that expression of V12Ras
      results in an increase in intracellular and in particular, mitochondrial reactive
      oxygen species. The ability of V12Ras to induce growth arrest and senescence is
      shown to be partially inhibited by coexpression of an activated rac1 gene. A more
      dramatic rescue of V12Ras-expressing cells is demonstrated when the cells are
      placed in a low oxygen environment, a condition in which reactive oxygen species
      production is inhibited. In addition, in a 1% oxygen environment, Ras is unable
      to trigger an increase in the level of the cyclin-dependent kinase inhibitor p21
      or to activate the senescent program. Under normoxic (20% O2) conditions, the
      V12Ras senescent phenotype is demonstrated to be unaffected by scavengers of
      superoxide but rescued by scavengers of hydrogen peroxide. These results suggest
      that in normal diploid cells, Ras proteins regulate oxidant production and that a
      rise in intracellular H2O2 represents a critical signal mediating replicative
      senescence.

PMID- 10075690
TI  - Inducible degradation of IkappaBalpha by the proteasome requires interaction with
      the F-box protein h-betaTrCP.
AB  - Activation of NF-kappaB transcription factors requires phosphorylation and
      ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide
      evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box
      protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for
      inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36
      phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36
      phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP
      inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32
      Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings
      indicate that betaTrCP is the adaptor protein required for IkappaBalpha
      recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and
      makes it a substrate for the proteasome.

PMID- 10075691
TI  - Reconstitution of insulin-sensitive glucose transport in fibroblasts requires
      expression of both PPARgamma and C/EBPalpha.
AB  - Adipocyte differentiation is regulated by at least two major transcription
      factors, CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome
      proliferator-activated receptor gamma (PPARgamma). Expression of PPARgamma in
      fibroblasts converts them to fat-laden cells with an adipocyte-like morphology.
      Here, we investigate the ability of PPARgamma to confer insulin-sensitive glucose
      transport to a variety of murine fibroblast cell lines. When cultured in the
      presence of a PPARgamma ligand, Swiss-3T3 and BALB/c-3T3 cells ectopically
      expressing PPARgamma accumulate lipid droplets, express C/EBPalpha, aP2, insulin
      responsive aminopeptidase, and glucose transporter isoform 4 (GLUT4), and exhibit
      highly insulin-responsive 2-deoxyglucose uptake. In contrast, PPARgamma
      expressing NIH-3T3 cells, despite similar lipid accumulation, adipocyte
      morphology, and aP2 expression, do not express C/EBPalpha or GLUT4 and fail to
      acquire insulin sensitivity. In cells ectopically expressing PPARgamma, the
      development of insulin-responsive glucose uptake correlates with C/EBPalpha
      expression. Furthermore, ectopic expression of C/EBPalpha in NIH-3T3 cells
      converts them to the adipocyte phenotype and restores insulin-sensitive glucose
      uptake. We propose that the pathway(s) leading to fat accumulation and
      morphological changes are distinct from that leading to insulin-dependent glucose
      transport. Our results suggest that although PPARgamma is sufficient to trigger
      the adipogenic program, C/EBPalpha is required for establishment of insulin
      sensitive glucose transport.

PMID- 10075692
TI  - Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor
      binding protein.
AB  - The principal component of Alzheimer's amyloid plaques, Abeta, derives from
      proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65
      is a brain-enriched protein that binds to APP. Although several laboratories have
      characterized the APP-FE65 interaction in vitro, the possible relevance of this
      interaction to Alzheimer's disease has remained unclear. We demonstrate here that
      APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in
      endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as
      well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent
      increase in Abeta secretion suggests that agents which inhibit the interaction of
      FE65 with APP might reduce Abeta secretion in the brain and therefore be useful
      for preventing or slowing amyloid plaque formation.

PMID- 10075693
TI  - Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at
      the G2/M phase transition in HeLa cells.
AB  - The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at
      mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B
      protein kinase and triggers mitosis. Although the active p34-cyclin B protein
      kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated
      the possibility that other kinases may initially trigger the phosphorylation and
      activation of p54(cdc25-c). We have examined the effects of the
      calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our
      in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and
      increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous
      population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II)
      or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II)
      results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25
      c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is
      no increase in histone H1 kinase activity. Our data suggest that a calcium
      calmodulin-dependent step may be involved in the initial activation of p54(cdc25
      c).

PMID- 10075694
TI  - Secretagogue-induced exocytosis recruits G protein-gated K+ channels to plasma
      membrane in endocrine cells.
AB  - Stimulation-regulated fusion of vesicles to the plasma membrane is an essential
      step for hormone secretion but may also serve for the recruitment of functional
      proteins to the plasma membrane. While studying the distribution of G protein
      gated K+ (KG) channels in the anterior pituitary lobe, we found KG channel
      subunits Kir3.1 and Kir3.4 localized on the membranes of intracellular dense core
      vesicles that contained thyrotropin. Stimulation of these thyrotroph cells with
      thyrotropin-releasing hormone provoked fusion of vesicles to the plasma membrane,
      increased expression of Kir3.1 and Kir3.4 subunits in the plasma membrane, and
      markedly enhanced KG currents stimulated by dopamine and somatostatin. These data
      indicate a novel mechanism for the rapid insertion of functional ion channels
      into the plasma membrane, which could form a new type of negative feedback
      control loop for hormone secretion in the endocrine system.

PMID- 10075695
TI  - The cell death-promoting gene DP5, which interacts with the BCL2 family, is
      induced during neuronal apoptosis following exposure to amyloid beta protein.
AB  - DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-inducing
      gene. To confirm that DP5 interacts with members of the Bcl-2 family, 293T cells
      were transiently co-transfected with DP5 and Bcl-xl cDNA constructs, and
      immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immunoprecipitated
      with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in
      mammalian cells. Previously, we reported that DP5 is induced during neuronal
      apoptosis in cultured sympathetic neurons. Here, we analyzed DP5 gene expression
      and the specific interaction of DP5 with Bcl-xl during neuronal death induced by
      amyloid-beta protein (A beta). DP5 mRNA was induced 6 h after treatment with A
      beta in cultured rat cortical neurons. The protein encoded by DP5 mRNA showed a
      specific interaction with Bcl-xl. Induction of DP5 gene expression was blocked by
      nifedipine, an inhibitor of L-type voltage-dependent calcium channels, and
      dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. These
      results suggested that the induction of DP5 mRNA occurs downstream of the
      increase in cytosolic calcium concentration caused by A beta. Moreover, DP5
      specifically interacts with Bcl-xl during neuronal apoptosis following exposure
      to A beta, and its binding could impair the survival-promoting activities of Bcl
      xl. Thus, the induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could
      play significant roles in neuronal degeneration following exposure to A beta.

PMID- 10075696
TI  - KSR-1 binds to G-protein betagamma subunits and inhibits beta gamma-induced
      mitogen-activated protein kinase activation.
AB  - The protein kinase KSR-1 is a recently identified participant in the Ras
      signaling pathway. The subcellular localization of KSR-1 is variable. In serum
      deprived cultured cells, KSR-1 is primarily found in the cytoplasm; in serum
      stimulated cells, a significant portion of KSR-1 is found at the plasma membrane.
      To identify the mechanism that mediates KSR-1 translocation, we performed a yeast
      two-hybrid screen. Three clones that interacted with KSR-1 were found to encode
      the full-length gamma10 subunit of heterotrimeric G-proteins. KSR-1 also
      interacted with gamma2 and gamma3 in a two-hybrid assay. Deletion analysis
      demonstrated that the isolated CA3 domain of KSR-1, which contains a cysteine
      rich zinc finger-like domain, interacted with gamma subunits.
      Coimmunoprecipitation experiments demonstrated that KSR-1 bound to beta1 gamma3
      subunits when all three were transfected into cultured cells. Lysophosphatidic
      acid treatment of cells induced KSR-1 translocation to the plasma membrane from
      the cytoplasm that was blocked by administration of pertussis toxin but not by
      dominant-negative Ras. Finally, transfection of wild-type KSR-1 inhibited beta1
      gamma3-induced mitogen-activated protein kinase activation in cultured cells.
      These results demonstrate that KSR-1 translocation to the plasma membrane is
      mediated, at least in part, by an interaction with beta gamma and that this
      interaction may modulate mitogen-activated protein kinase signaling.

PMID- 10075697
TI  - Fas ligand-independent, FADD-mediated activation of the Fas death pathway by
      anticancer drugs.
AB  - Trimerization of the Fas receptor (CD95, APO-1), a membrane bound protein,
      triggers cell death by apoptosis. The main death pathway activated by Fas
      receptor involves the adaptor protein FADD (for Fas-associated death domain) that
      connects Fas receptor to the caspase cascade. Anticancer drugs have been shown to
      enhance both Fas receptor and Fas ligand expression on tumor cells. The
      contribution of Fas ligand-Fas receptor interactions to the cytotoxic activity of
      these drugs remains controversial. Here, we show that neither the antagonistic
      anti-Fas antibody ZB4 nor the Fas-IgG molecule inhibit drug-induced apoptosis in
      three different cell lines. The expression of Fas ligand on the plasma membrane,
      which is identified in untreated U937 human leukemic cells but remains
      undetectable in untreated HT29 and HCT116 human colon cancer cell lines, is not
      modified by exposure to various cytotoxic agents. These drugs induce the
      clustering of Fas receptor, as observed by confocal laser scanning microscopy,
      and its interaction with FADD, as demonstrated by co-immunoprecipitation.
      Overexpression of FADD by stable transfection sensitizes tumor cells to drug
      induced cell death and cytotoxicity, whereas down-regulation of FADD by transient
      transfection of an antisense construct decreases tumor cell sensitivity to drug
      induced apoptosis. These results were confirmed by transient transfection of
      constructs encoding either a FADD dominant negative mutant or MC159 or E8 viral
      proteins that inhibit the FADD/caspase-8 pathway. These results suggest that drug
      induced cell death involves the Fas/FADD pathway in a Fas ligand-independent
      fashion.

PMID- 10075698
TI  - Osmotic response element is required for the induction of aldose reductase by
      tumor necrosis factor-alpha.
AB  - Induction of aldose reductase (AR) was observed in human cells treated with tumor
      necrosis factor-alpha (TNF-alpha). AR protein expression increased severalfold in
      human liver cells after 1 day of exposure to 100 units/ml TNF-alpha. An increase
      in AR transcripts was also observed in human liver cells after 3 h of TNF-alpha
      treatment, reaching a maximum level of 11-fold at 48 h. Among the three
      inflammatory cytokines: TNF-alpha, interleukin-1, and interferon-gamma, TNF-alpha
      (100 units/ml) gave the most induction of AR. Differences in the pattern of AR
      induction were observed in human liver, lens, and retinal pigment epithelial
      cells with increasing concentrations of TNF-alpha. A similar pattern of AR
      promoter response was observed between TNF-alpha and osmotically stressed human
      liver cells. The deletion of the osmotic response element (ORE) abolished the
      induction by TNF-alpha and osmotic stress. A point mutation that converts ORE to
      a nuclear factor-kappaB (NF-kappaB) sequence abolished the osmotic response but
      maintained the TNF-alpha response. Electrophoretic gel mobility shift assays
      showed two NF-kappaB proteins, p50 and p52, capable of binding ORE sequence, and
      gel shift Western assay detected NF-kappaB proteins p50 and p65 in the ORE
      complex. Inhibitors of NF-kappaB signaling, lactacystin, and MG132 abolished the
      AR promoter response to TNF-alpha.

PMID- 10075699
TI  - Lack of enhancer function in mammals is unique to oocytes and fertilized eggs.
AB  - Previous studies have shown that the lack of novel coactivator activity in mouse
      oocytes and one-cell embryos (fertilized eggs) renders them incapable of
      utilizing Gal4:VP16-dependent enhancers (distal elements) but not promoters
      (proximal elements) in regulating transcription. This coactivator activity first
      appears in two- to four-cell embryos coincident with the major activation of
      zygotic gene expression. Here we show that whereas oocytes and fertilized eggs
      could utilize Sp1-dependent promoters, they could not utilize Sp1-dependent
      enhancers, although they showed promoter repression, which is a requirement for
      delineating enhancer function. In contrast, both Sp1-dependent promoters and
      enhancers were functional in two- to four-cell embryos. Furthermore, the same
      embryonic stem cell mRNA that provided the coactivator activity for Gal4:VP16
      dependent enhancer function also provided Sp1-dependent enhancer function in
      oocytes. Therefore, the coactivator activity appears to be a requirement for
      general enhancer function. To determine whether the absence of enhancer function
      is a unique property of oocytes or a general property of other terminally
      differentiated cells, transcription was examined in terminally differentiated hNT
      neurons and their precursors, undifferentiated NT2 stem cells. The results showed
      that both cell types could utilize enhancers and promoters. Thus, in mammals, the
      lack of enhancer function appears to be unique to oocytes and fertilized eggs,
      suggesting that it provides a safeguard against premature activation of genes
      prior to zygotic gene expression during development.

PMID- 10075700
TI  - Calmodulin-binding sites on adenylyl cyclase type VIII.
AB  - Ca2+ stimulation of adenylyl cyclase type VIII (ACVIII) occurs through loosely
      bound calmodulin. However, where calmodulin binds in ACVIII and how the binding
      activates this cyclase have not yet been investigated. We have located two
      putative calmodulin-binding sites in ACVIII. One site is located at the N
      terminus as revealed by overlay assays; the other is located at the C terminus,
      as indicated by mutagenesis studies. Both of these calmodulin-binding sites were
      confirmed by synthetic peptide studies. The N-terminal site has the typical motif
      of a Ca2+-dependent calmodulin-binding domain, which is defined by a
      characteristic pattern of hydrophobic amino acids, basic and aromatic amino
      acids, and a tendency to form amphipathic alpha-helix structures. Functional,
      mutagenesis studies suggest that this binding makes a minor contribution to the
      Ca2+ stimulation of ACVIII activity, although it might be involved in calmodulin
      trapping by ACVIII. The primary structure of the C-terminal site resembles
      another calmodulin-binding motif, the so-called IQ motif, which is commonly Ca2+
      independent. Mutagenesis and functional assays indicate that this latter site is
      a calcium-dependent calmodulin-binding site, which is largely responsible for the
      Ca2+ stimulation of ACVIII. Removal of this latter calmodulin-binding region from
      ACVIII results in a hyperactivated enzyme state and a loss of Ca2+ sensitivity.
      Thus, Ca2+/calmodulin regulation of ACVIII may be through a disinhibitory
      mechanism, as is the case for a number of other targets of Ca2+/calmodulin.

PMID- 10075701
TI  - Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a
      function of activation.
AB  - p21-activated protein kinase (PAK) is a family of serine/threonine kinases whose
      activity is stimulated by binding to small G-proteins such as Cdc42 and
      subsequent autophosphorylation. Focusing on the ubiquitous gamma-isoform of PAK
      in this study, baculovirus-infected insect cells were used to obtain recombinant
      gamma-PAK, while native gamma-PAK was isolated from rabbit reticulocytes. Two
      dimensional gel electrophoresis of gamma-PAK followed by immunoblot analysis
      revealed a similar profile for native and recombinant gamma-PAK, both consisting
      of multiple protein spots. Following Cdc42-stimulated autophosphorylation, the
      two-dimensional profiles of native and recombinant gamma-PAK were characterized
      by a similar acidic shift, suggesting a common response to Cdc42. To understand
      the effect of differential phosphorylation on its activation status, gamma-PAK
      autophosphorylation was conducted in the presence or absence of activators such
      as Cdc42 and histone II-AS, followed by tryptic digestion and comparative two
      dimensional phosphopeptide mapping. The major phosphopeptides were subjected to a
      combination of manual and automated amino acid sequencing. Overall, eight
      autophosphorylation sites were identified in Cdc42-activated gamma-PAK, six of
      which are in common with those previously reported in alpha-PAK, while Ser-19 and
      Ser-165 appear to be uniquely phosphorylated in the gamma-form. Further, the
      phosphorylation of Ser-141, Ser-165, and Thr-402 was found to correlate with
      gamma-PAK activation.

PMID- 10075702
TI  - Heparin-induced conformational change in microtubule-associated protein Tau as
      detected by chemical cross-linking and phosphopeptide mapping.
AB  - In Alzheimer's disease, microtubule-associated protein tau becomes abnormally
      phosphorylated and aggregates into paired helical filaments. Sulfated
      glycosaminoglycans such as heparin and heparan sulfate were shown to accumulate
      in pretangle neurons, stimulate in vitro tau phosphorylation, and cause tau
      aggregation into paired helical filament-like filaments. The sulfated
      glycosaminoglycan-tau interaction was suggested to be the central event in the
      development of neuropathology in Alzheimer's disease brain (Goedert, M., Jakes,
      R., Spillantini, M. G., Hasegawa, M., Smith, M. J., and Crowther, R. A. (1996)
      Nature 383, 550-553). The biochemical mechanism by which sulfated
      glycosaminoglycans stimulate tau phosphorylation and cause tau aggregation
      remains unclear. In this study, disuccinimidyl suberate (DSS), a bifunctional
      chemical cross-linker, cross-linked tau dimers, tetramers, high molecular size
      aggregates, and two tau species of sizes 72 and 83 kDa in the presence of
      heparin. In the absence of heparin only dimeric tau was cross-linked by DSS. Fast
      protein liquid chromatography gel filtration revealed that 72- and 83-kDa species
      were formed by intramolecular cross-linking of tau by DSS. These observations
      indicate that heparin, in addition to causing aggregation, also induces a
      conformational change in tau in which reactive groups are unmasked or move closer
      leading to the DSS cross-linking of 72- and 83-kDa species. Heparin-induced
      structural changes in tau molecule depended on time of heparin exposure.
      Dimerization and tetramerization peaked at 48 h, whereas conformational change
      was completed within 30 min of heparin exposure. Heparin exposure beyond 48 h
      caused an abrupt aggregation of tau into high molecular size species. Heparin
      stimulated tau phosphorylation by neuronal cdc2-like kinase (NCLK) and cAMP
      dependent protein kinase. Phosphopeptide mapping and phosphopeptide sequencing
      revealed that tau is phosphorylated by NCLK on Thr212 and Thr231 and by cAMP
      dependent protein kinase on Ser262 only in the presence of heparin. Heparin
      stimulation of tau phosphorylation by NCLK showed dependence on time of heparin
      exposure and correlated with the heparin-induced conformational change of tau.
      Our data suggest that heparin-induced conformational change exposes new sites for
      phosphorylation within tau molecule.

PMID- 10075703
TI  - Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis.
AB  - Endothelial cell death may contribute to tissue injury from ischemia. Little is
      known, however, about the characteristics of endothelial cell death in response
      to hypoxia. Using an in vitro model, we found that human umbilical vein
      endothelial cells were resistant to hypoxia-induced cell death with only a 2%
      reduction in viability at 24 h and 45% reduction in viability at 48 h.
      Overexpression of a mutant, IkappaBalpha, via adenoviral vector did not
      potentiate cell death in hypoxia, indicating that nuclear factor-kappaB
      activation was not involved in cytoprotection. Cell death in hypoxia was
      determined to be apoptotic by 3' labeling of DNA using terminal deoxynucleotidyl
      transferase staining and reversibility of cell death with a caspase inhibitor.
      Exposure of endothelial cells to hypoxia did not alter levels of proapoptotic and
      antiapoptotic Bcl-2 family members Bax and Bcl-XL by immunoblot analysis. In
      contrast, changes in p53 protein levels correlated with the induction of
      apoptosis in hypoxic endothelial cells. Inhibition of the proteasome increased
      p53 protein levels and accelerated cell death in hypoxia. Overexpression of p53
      by adenoviral transduction was sufficient to initiate apoptosis of normoxic
      endothelial cells. These data provide a framework for the study of factors
      regulating endothelial cell survival and death in hypoxia.

PMID- 10075704
TI  - Sialyltransferase isoforms are phosphorylated in the cis-medial Golgi on serine
      and threonine residues in their luminal sequences.
AB  - ST6Gal-I (alpha2,6-sialyltransferase) is expressed as two isoforms, STTyr and
      STCys, which exhibit differences in catalytic activity, trafficking through the
      secretory pathway, and proteolytic processing and secretion. We have found that
      the ST6Gal-I isoforms are phosphorylated on luminal Ser and Thr residues.
      Immunoprecipitation of 35S- and 32P-labeled proteins expressed in COS-1 cells
      suggests that the STTyr isoform is phosphorylated to a greater extent than the
      STCys isoform. Analysis of domain deletion mutants revealed that STTyr is
      phosphorylated on stem and catalytic domain amino acids, whereas STCys is
      phosphorylated on catalytic domain amino acids. An endoplasmic reticulum
      retained/retrieved chimeric Iip33-ST protein demonstrates drastically lower
      phosphorylation than does the wild type STTyr isoform. This suggests that the
      bulk of the ST6Gal-I phosphorylation is occurring in the Golgi. Treatment of
      cells with the ionophore monensin does not significantly block phosphorylation of
      the STTyr isoform, suggesting that phosphorylation is occurring in the cis-medial
      Golgi prior to the monensin block. This study demonstrates the presence of kinase
      activities in the cis-medial Golgi and the substantial phosphorylation of the
      luminal sequences of a glycosyltransferase.

PMID- 10075705
TI  - alpha-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed
      in pancreatic beta cells and functions in insulin but not gamma-aminobutyric acid
      secretion.
AB  - The function of soluble N-ethylmaleimide-sensitive attachment protein-alpha
      (alpha-SNAP) in exocytosis still remains obscure. This study was conducted to
      determine the physiological role of alpha-SNAP in the secretion of insulin and
      gamma-aminobutryric acid (GABA) from pancreatic beta cells. Reverse transcriptase
      polymerase chain reaction analysis of total RNA isolated from rat islets
      disclosed alpha-SNAP, but not beta-SNAP, mRNA expression, and an
      immunofluorescence study of rat pancreas showed that alpha-SNAP was present
      predominantly in the cytoplasm of the islets of Langerhans. alpha-SNAP
      overexpression in rat islets enhanced insulin release relative to the control
      levels. An in vitro binding study showed that both wild-type alpha-SNAP and C
      terminal-deleted alpha-SNAP mutant (1-285) can bind to syntaxin 1A. alpha-SNAP
      mutant (1-285) was overexpressed to evaluate its activity as dominant-negative
      effector on insulin release. Overexpression of alpha-SNAP mutant (1-285) in rat
      islets and MIN6 cells decreased glucose-stimulated insulin release to about 50%
      of the control levels. Suppression of endogeneous alpha-SNAP in MIN6 cells by
      treatment with an antisense phosphorothioate oligonucleotide resulted in
      inhibition of insulin release. In order to examine if alpha-SNAP functions in
      exocytosis from synaptic-like microvesicles in pancreatic beta cells, the
      functional role of alpha-SNAP in GABA release from MIN6 cells was studied. The
      data showed no effect of alpha-SNAP mutant (1-285) overexpression on GABA
      release. We conclude that 1) alpha-SNAP plays a crucial role in insulin
      exocytosis via large dense core vesicles, but not GABA released via synaptic-like
      microvesicles, in pancreatic beta cells; and 2) the interaction of alpha-SNAP and
      syntaxin 1A may play an important role in the insulin exocytotic process.

PMID- 10075706
TI  - Hierarchy of sorting signals in chimeras of intestinal lactase-phlorizin
      hydrolase and the influenza virus hemagglutinin.
AB  - Lactase-phlorizin hydrolase (LPH) is an apical protein in intestinal cells. The
      location of sorting signals in LPH was investigated by preparing a series of
      mutants that lacked the LPH cytoplasmic domain or had the cytoplasmic domain of
      LPH replaced by sequences that comprised basolateral targeting signals and
      overlapping internalization signals of various potency. These signals are mutants
      of the cytoplasmic domain of the influenza hemagglutinin (HA), which have been
      shown to be dominant in targeting HA to the basolateral membrane. The LPH-HA
      chimeras were expressed in Madin-Darby canine kidney (MDCK) and colon carcinoma
      (Caco-2) cells, and their transport to the cell surface was analyzed. All of the
      LPH mutants were targeted correctly to the apical membrane. Furthermore, the LPH
      HA chimeras were internalized, indicating that the HA tails were available to
      interact with the cytoplasmic components of clathrin-coated pits. The
      introduction of a strong basolateral sorting signal into LPH was not sufficient
      to override the strong apical signals of the LPH external domain or transmembrane
      domains. These results show that basolateral sorting signals are not always
      dominant over apical sorting signals in proteins that contain each and suggest
      that sorting of basolateral from apical proteins occurs within a common
      compartment where competition for sorting signals can occur.

PMID- 10075707
TI  - A mutation in the C-terminal putative Zn2+ finger motif of UL52 severely affects
      the biochemical activities of the HSV-1 helicase-primase subcomplex.
AB  - Herpes simplex virus type 1 encodes a heterotrimeric helicase-primase complex
      that is composed of the products of the UL5, UL52, and UL8 genes. A subcomplex
      consisting of the UL5 and UL52 proteins retains all the enzymatic activities
      exhibited by the holoenzyme in vitro. The UL52 protein contains a putative zinc
      finger at its C terminus which is highly conserved among both prokaryotic and
      eukaryotic primases. We constructed a mutation in which two highly conserved
      cysteine residues in the zinc finger motif were replaced with alanine residues. A
      UL52 expression plasmid containing the mutation in the zinc finger region is
      unable to support the growth of a UL52 mutant virus in a transient
      complementation assay. Wild type and mutant UL5.UL52 subcomplexes were purified
      from insect cells infected with recombinant baculoviruses. Surprisingly, the
      mutant protein was severely affected in all biochemical activities tested; no
      helicase or primase activities could be detected, and the mutant protein retains
      only about 9% of wild type levels of single-stranded DNA-dependent ATPase
      activity. Gel mobility shift assays showed that DNA binding is severely affected
      as well; the mutant subcomplex only retains approximately 8% of wild type levels
      of binding to a forked substrate. On the other hand, the mutant protein retains
      its ability to interact with UL5 as indicated by copurification and with UL8 as
      indicated by a supershifted band in the gel mobility shift assay. In addition,
      the ability of individual subunits to bind single-stranded DNA was examined by
      photo cross-linking. In the wild type UL5.UL52 subcomplex, both subunits are able
      to bind an 18-mer of oligo(dT). The mutant subcomplex was severely compromised in
      the ability of both UL5 and UL52 to bind the oligonucleotide; total cross-linking
      was only 2% of wild type levels. These results are consistent with the proposal
      that the putative zinc binding motif of UL52 is required not only for binding of
      the UL52 subunit to DNA and for primase activity but also for optimal binding of
      UL5 to DNA and for the subsequent ATPase and helicase activities.

PMID- 10075708
TI  - Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits
      are divergently transcribed from a common promoter region.
AB  - Human HADHA and HADHB genes encode the subunits of an enzyme complex, the
      trifunctional protein, involved in mitochondrial beta-oxidation of fatty acids.
      Both genes are located in the same region of chromosome 2p23. We isolated genomic
      clones, including 5' flanking regions, for HADHA and HADHB. Sequencing revealed
      that both of these genes are linked in a head-to-head arrangement on opposite
      strands and have in common a 350-bp 5' flanking region. The 5' flanking region
      has bidirectional promoter activity within this region; two cis elements proved
      critical for the activity. Transcription factor Sp1 functions as an activator for
      the bidirectional promoter by binding to both elements. Therefore, expression of
      trifunctional protein subunits are probably coordinately regulated by a common
      promoter and by Sp1.

PMID- 10075709
TI  - Structure and function of the human transcription elongation factor DSIF.
AB  - 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) is a classic inhibitor of
      transcription elongation by RNA polymerase II (pol II). We have previously
      identified and purified a novel transcription elongation factor, termed DSIF (for
      DRB sensitivity-inducing factor), that makes transcription sensitive to DRB. DSIF
      is composed of 160- and 14-kDa subunits, which are homologs of the Saccharomyces
      cerevisiae transcription factors Spt5 and Spt4. DSIF may either repress or
      stimulate transcription in vitro, depending on conditions, but its physiological
      function remains elusive. Here we characterize the structure and function of DSIF
      p160. p160 is shown to be a ubiquitous nuclear protein that forms a stable
      complex with p14 and interacts directly with the pol II largest subunit. Mutation
      analysis of p160 is used to identify structural features essential for its in
      vitro activity and to map the domains required for its interaction with p14 and
      pol II. Finally, a p160 mutant that represses DSIF activity in a dominant
      negative manner is identified and used to demonstrate that DSIF represses
      transcription from various promoters in vivo.

PMID- 10075710
TI  - Cell shrinkage regulates Src kinases and induces tyrosine phosphorylation of
      cortactin, independent of the osmotic regulation of Na+/H+ exchangers.
AB  - The signaling pathways by which cell volume regulates ion transporters, e.g.
      Na+/H+ exchangers (NHEs), and affects cytoskeletal organization are poorly
      understood. We have previously shown that shrinkage induces tyrosine
      phosphorylation in CHO cells, predominantly in an 85-kDa band. To identify volume
      sensitive kinases and their substrates, we investigated the effect of
      hypertonicity on members of the Src kinase family. Hyperosmolarity stimulated Fyn
      and inhibited Src. Fyn activation was also observed in nystatin-permeabilized
      cells, where shrinkage cannot induce intracellular alkalinization. In contrast,
      osmotic inhibition of Src was prevented by permeabilization or by inhibiting NHE
      1. PP1, a selective Src family inhibitor, strongly reduced the hypertonicity
      induced tyrosine phosphorylation. We identified one of the major targets of the
      osmotic stress-elicited phosphorylation as cortactin, an 85-kDa actin-binding
      protein and well known Src family substrate. Cortactin phosphorylation was
      triggered by shrinkage and not by changes in osmolarity or pHi and was abrogated
      by PP1. Hyperosmotic cortactin phosphorylation was reduced in Fyn-deficient
      fibroblasts but remained intact in Src-deficient fibroblasts. To address the
      potential role of the Src family in the osmotic regulation of NHEs, we used PP1.
      The drug affected neither the hyperosmotic stimulation of NHE-1 nor the
      inhibition of NHE-3. Thus, members of the Src family are volume-sensitive enzymes
      that may participate in the shrinkage-related reorganization of the cytoskeleton
      but are probably not responsible for the osmotic regulation of NHE.

PMID- 10075711
TI  - Endothelin stimulates glucose uptake and GLUT4 translocation via activation of
      endothelin ETA receptor in 3T3-L1 adipocytes.
AB  - Endothelin-1 (ET-1) is a 21-amino acid peptide that binds to G-protein-coupled
      receptors to evoke biological responses. This report studies the effect of ET-1
      on regulating glucose transport in 3T3-L1 adipocytes. ET-1, but not angiotensin
      II, stimulated glucose uptake in a dose-dependent manner with an EC50 value of
      0.29 nM and a 2.47-fold stimulation at 100 nM. ET-1 stimulated glucose uptake in
      differentiated 3T3-L1 cells but had no effect in undifferentiated cells, although
      ET-1 stimulated phosphatidylinositol hydrolysis to a similar degree in both. The
      3T3-L1 cells expressed approximately 560,000 sites/cell of ETA receptor, which
      was not altered during differentiation. Western blot analysis and
      immunofluorescence staining show that ET-1 stimulated the translocation of
      insulin-responsive aminopeptidase and GLUT4 to the plasma membrane. The effect of
      ET-1 on glucose uptake was blocked by A-216546, an antagonist selective for the
      ETA receptor. ET-1 treatment did not induce phosphorylation of insulin receptor
      beta-subunit, insulin receptor substrate-1, or Akt but stimulated the tyrosyl
      phosphorylation of a 75-kDa protein. Genistein (100 microM), an inhibitor of
      tyrosine kinases, inhibited ET-1-stimulated glucose uptake. Our results show that
      ET-1 stimulates GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes via
      activation of ETA receptor.

PMID- 10075712
TI  - Mutational analysis of cell cycle inhibition by integrin beta1C.
AB  - Integrin beta1C is an alternatively spliced cytoplasmic variant of the beta1
      subunit that potently inhibits cell cycle progression. In this study, we analyzed
      the requirements for growth suppression by beta1C. A chimera containing the
      extracellular/transmembrane domain of the Tac subunit of the human interleukin 2
      receptor (gp55) fused to the cytoplasmic domain of beta1C (residues 732-805)
      strongly inhibited growth in mouse 10T1/2 cells even at low expression levels,
      whereas chimeras containing the beta1A, beta1B, beta1D, beta3, and beta5
      cytoplasmic domains had weak and variable effects. The beta1C cytoplasmic domain
      is composed of a membrane proximal region (732-757) common to all beta1 variants
      and a COOH-terminal 48-amino acid domain (758-805) unique to beta1C. The beta1C
      specific domain (758-805) was sufficient to block cell growth even when expressed
      as a soluble cytoplasmic green fluorescent protein fusion protein. These results
      indicate that growth inhibition by beta1C does not require the intact receptor
      and can function in the absence of membrane targeting. Analysis of deletions
      within the beta1C-specific domain showed that the 18-amino acid sequence 775-792
      is both necessary and sufficient for maximal growth inhibition, although the 13
      COOH-terminal residues (793-805) also had weak activity. Finally, beta1C is known
      to be induced in endothelial cells in response to tumor necrosis factor and is
      down-regulated in prostate epithelial cells after transformation. The green
      fluorescent protein/beta1C (758-805) chimera blocked growth in the human
      endothelial cell line EV304 and in the transformed prostate epithelial cell line
      DU145, consistent with a role for beta1C as a growth inhibitor in vivo.

PMID- 10075713
TI  - Primary structure, tissue distribution, and expression of mouse phosphoinositide
      dependent protein kinase-1, a protein kinase that phosphorylates and activates
      protein kinase Czeta.
AB  - Phosphoinositide-dependent protein kinase-1 (PDK1) is a recently identified
      serine/threonine kinase that phosphorylates and activates Akt and p70(S6K), two
      downstream kinases of phosphatidylinositol 3-kinase. To further study the
      potential role of PDK1, we have screened a mouse liver cDNA library and
      identified a cDNA encoding the enzyme. The predicted mouse PDK1 (mPDK1) protein
      contained 559 amino acids and a COOH-terminal pleckstrin homology domain. A 7
      kilobase mPDK1 mRNA was broadly expressed in mouse tissues and in embryonic
      cells. In the testis, a high level expression of a tissue-specific 2-kilobase
      transcript was also detected. Anti-mPDK1 antibody recognized multiple proteins in
      mouse tissues with molecular masses ranging from 60 to 180 kDa. mPDK1
      phosphorylated the conserved threonine residue (Thr402) in the activation loop of
      protein kinase C-zeta and activated the enzyme in vitro and in cells. Our
      findings suggest that there may be different isoforms of mPDK1 and that the
      protein is an upstream kinase that activates divergent pathways downstream of
      phosphatidylinositol 3-kinase.

PMID- 10075714
TI  - RIN ZF, a novel zinc finger gene, encodes proteins that bind to the CACC element
      of the gastrin promoter.
AB  - Expression of gastrin, a gut hormone and growth factor, has tissue-specific
      transcriptional regulation and can be induced in some tumors. Previous studies
      have shown that a CACC cis-regulatory element is important for transcriptional
      activation in pancreatic insulinoma cells. To identify CACC-binding proteins, a
      lambda phage cDNA library derived from a rat insulinoma cell line, RIN 38A, was
      screened by a Southwestern method. A novel member of the Cys2-His2 zinc finger
      gene family was cloned and designated RIN ZF, having a cDNA sequence of 3.8
      kilobases. One full-length and a shorter splice variant were sequenced and had
      predicted protein masses of 91.6 and 88.7 kDa. Expression of both splice forms
      were ubiquitous in fetal and adult rat tissues. Recombinant RIN ZF protein
      exhibited sequence-specific binding to the gastrin CACC element in a gel mobility
      shift assay. In transient transfections, both splice variants appeared to have
      only weak activating effects on gastrin-luciferase reporter gene transcription.
      Furthermore, RIN ZF coexpression with Sp1 appeared to block the strongly
      activating effects of Sp1 mediated through the CACC element. These findings
      suggest that a novel set of zinc finger proteins may help regulate gastrin gene
      expression by interfering with Sp1 transactivation.

PMID- 10075715
TI  - Interaction between the skeletal muscle type 1 Na+ channel promoter E-box and an
      upstream repressor element. Release of repression by myogenin.
AB  - We have defined how four elements that regulate expression of the rat skeletal
      muscle type 1 sodium channel (SkM1) gene cooperate to yield specific expression
      in differentiated muscle. A basal promoter region containing within it a promoter
      E-box (-31/-26) is broadly expressed in many cells, including myoblasts and
      myotubes; mutations within the promoter E-box that disrupt binding of the
      myogenic basic helix-loop-helix (bHLH) factors reduce expression in all cell
      types only slightly. Sequential addition of upstream elements to the wild-type
      promoter confer increasing specificity of expression in differentiated cells,
      even though all three upstream elements, including a positive element (-85/-57),
      a repressor E-box (-90/-85), and upstream repressor sequences (-135/-95), bind
      ubiquitously expressed transcription factors. Mutations in the promoter E-box
      that disrupt the binding of the bHLH factors counteract the specificity conferred
      by addition of the upstream elements, with the greatest interaction observed
      between the upstream repressor sequences and the promoter E-box. Forced
      expression of myogenin in myoblasts releases repression exerted by the upstream
      repressor sequences in conjunction with the wild-type, but not mutant, promoter E
      box, and also initiates expression of the endogenous SkM1 protein. Our data
      suggest that particular myogenic bHLH proteins bound at the promoter E-box
      control expression of SkM1 by releasing repression exerted by upstream repressor
      sequences in differentiated muscle cells.

PMID- 10075716
TI  - Structural details of proteinase entrapment by human alpha2-macroglobulin emerge
      from three-dimensional reconstructions of Fab labeled native, half-transformed,
      and transformed molecules.
AB  - Three-dimensional electron microscopy reconstructions of native, half
      transformed, and transformed alpha2-macroglobulins (alpha2Ms) labeled with a
      monoclonal Fab Fab offer new insight into the mechanism of its proteinase
      entrapment. Each alpha2M binds four Fabs, two at either end of its dimeric
      protomers approximately 145 A apart. In the native structure, the epitopes are
      near the base of its two chisel-like features, laterally separated by 120 A,
      whereas in the methylamine-transformed alpha2M, the epitopes are at the base of
      its four arms, laterally separated by 160 A. Upon thiol ester cleavage, the
      chisels on the native alpha2M appear to split with a separation and rotation to
      give the four arm-like extensions on transformed alpha2M. Thus, the receptor
      binding domains previously enclosed within the chisels are exposed. The labeled
      structures further indicate that the two protomeric strands that constitute the
      native and transformed molecules are related and reside one on each side of the
      major axes of these structures. The half-transformed structure shows that the two
      Fabs at one end of the molecule have an arrangement similar to those on the
      native alpha2M, whereas on its transformed end, they have rotated. The rotation
      is associated with a partial untwisting of the strands and an enlargement of the
      openings to the cavity. We propose that the enlarged openings permit the entrance
      of the proteinase. Then cleavage of the remaining bait domains by a second
      proteinase occurs with its entrance into the cavity. This is followed by a
      retwisting of the strands to encapsulate the proteinases and expose the receptor
      binding domains associated with the transformed alpha2M.

PMID- 10075717
TI  - Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3.
AB  - Drosophila transcription factor cubitus interruptus (Ci) and its co-activator CRE
      (cAMP response element)-binding protein (CBP) activate a group of target genes on
      the anterior-posterior border in response to hedgehog protein (Hh) signaling. In
      the anterior region, in contrast, the carboxyl-truncated form of Ci generated by
      protein processing represses Hh expression. In vertebrates, three Ci-related
      transcription factors (glioblastoma gene products (GLIs) 1, 2, and 3) were
      identified, but their functional difference in Hh signal transduction is unknown.
      Here, we report distinct roles for GLI1 and GLI3 in Sonic hedgehog (Shh)
      signaling. GLI3 containing both repression and activation domains acts both as an
      activator and a repressor, as does Ci, whereas GLI1 contains only the activation
      domain. Consistent with this, GLI3, but not GLI1, is processed to generate the
      repressor form. Transcriptional co-activator CBP binds to GLI3, but not to GLI1.
      The trans-activating capacity of GLI3 is positively and negatively regulated by
      Shh and cAMP-dependent protein kinase, respectively, through a specific region of
      GLI3, which contains the CBP-binding domain and the phosphorylation sites of cAMP
      dependent protein kinase. GLI3 directly binds to the Gli1 promoter and induces
      Gli1 transcription in response to Shh. Thus, GLI3 may act as a mediator of Shh
      signaling in the activation of the target gene Gli1.

PMID- 10075718
TI  - A circularized sodium-calcium exchanger exon 2 transcript.
AB  - Previous reports of Na/Ca exchanger gene 1 (NCX1) expression have revealed a
      major RNA transcript of 7 kilobase pairs (kb), minor transcripts of approximately
      13 and approximately 4 kb, and a relatively abundant 1.8-kb RNA band. In the
      present report we demonstrate that the 1.8-kb message, which has a tissue and
      subcellular distribution matching that of full-length NCX1 but is not
      polyadenylated, corresponds to a perfectly circularized exon 2 species. The
      circular transcript contained the normal NCX1 start codon, a new stop codon
      introduced as a consequence of circularization, and encoded a protein
      corresponding to the NH2-terminal portion of NCX1, terminating just after amino
      acid 600 in the cytoplasmic loop. A linear version of the circular transcript was
      prepared and transfected into HEK-293 cells. A protein, matching the predicted
      size of approximately 70 kDa, was expressed, and the transfected cells possessed
      Na/Ca exchange activity. Although in native tissue we could not detect a protein
      corresponding exactly to that predicted from the circular transcript, a prominent
      band of slightly shorter size, possibly representing further proteolytic
      processing of circular transcript protein, was observed in membranes from LLC-MK2
      cells and rat kidney.

PMID- 10075719
TI  - Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet
      light.
AB  - The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest
      of which (p90) binds to and inactivates the p53 tumor suppressor protein.
      Multiple MDM2 proteins have been detected in tumors and in cell lines expressing
      high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is
      expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts,
      indicating that it may have an important physiological role in normal cells.
      Expression of this protein is induced, as is that of p90, by UV light in a p53
      dependent manner. The p76 protein is synthesized via translational initiation at
      AUG codon 50 and thus lacks the N terminus of p90 and does not bind p53. In
      cells, p90 and p76 can be synthesized from mdm2 mRNAs transcribed from both the
      P1 (constitutive) and P2 (p53-responsive) promoters. Site-directed mutagenesis
      reveals that these RNAs give rise to p76 via internal initiation of translation.
      In addition, mdm2 mRNAs lacking exon 3 give rise to p76 exclusively, and such
      mRNAs are induced by p53 in response to UV light. These data indicate that p76
      may be an important product of the mdm2 gene and a downstream effector of p53.

PMID- 10075720
TI  - Inhibition of DNA supercoiling-dependent transcriptional activation by a distant
      B-DNA to Z-DNA transition.
AB  - Negative DNA superhelicity can destabilize the local B-form DNA structure and can
      drive transitions to other conformations at susceptible sites. In a molecule
      containing multiple susceptible sites, superhelicity can couple these
      alternatives together, causing them to compete. In principle, these
      superhelically driven local structural transitions can be either facilitated or
      inhibited by proteins that bind at or near potential transition sites. If a DNA
      region that is susceptible to forming a superhelically induced alternate
      structure is stabilized in the B-form by a DNA-binding protein, its propensity
      for transition will be transferred to other sites within the same domain. If one
      of these secondary sites is in a promoter region, this transfer could facilitate
      open complex formation and thereby activate gene expression. We previously
      proposed that a supercoiling-dependent, DNA structural transmission mechanism of
      this type is responsible for the integration host factor-mediated activation of
      transcription from the ilvPG promoter of Escherichia coli (Sheridan, S. D.,
      Benham, C. J. & Hatfield, G. W. (1998) J. Biol. Chem. 273, 21298-21308). In this
      report we confirm the validity of this mechanism by demonstrating the ability of
      a distant Z-DNA-forming site to compete with the superhelical destabilization
      that is required for integration host factor-mediated transcriptional activation,
      and thereby delay its occurrence.

PMID- 10075721
TI  - Cloning and characterization of human guanine deaminase. Purification and partial
      amino acid sequence of the mouse protein.
AB  - Mouse erythrocyte guanine deaminase has been purified to homogeneity. The native
      enzyme was dimeric, being comprised of two identical subunits of approximately
      50,000 Da. The protein sequence was obtained from five cyanogen bromide cleavage
      products giving sequences ranging from 12 to 25 amino acids in length and
      corresponding to 99 residues. Basic Local Alignment Search Tool (BLAST) analysis
      of expressed sequence databases enabled the retrieval of a human expressed
      sequence tag cDNA clone highly homologous to one of the mouse peptide sequences.
      The presumed coding region of this clone was used to screen a human kidney cDNA
      library and secondarily to polymerase chain reaction-amplify the full-length
      coding sequence of the human brain cDNA corresponding to an open reading frame of
      1365 nucleotides and encoding a protein of 51,040 Da. Comparison of the mouse
      peptide sequences with the inferred human protein sequence revealed 88 of 99
      residues to be identical. The human coding sequence of the putative enzyme was
      subcloned into the bacterial expression vector pMAL-c2, expressed, purified, and
      characterized as having guanine deaminase activity with a Km for guanine of 9.5
      +/- 1.7 microM. The protein shares a 9-residue motif with other aminohydrolases
      and amidohydrolases (PGX[VI]DXH[TVI]H) that has been shown to be ligated with
      heavy metal ions, commonly zinc. The purified recombinant guanine deaminase was
      found to contain approximately 1 atom of zinc per 51-kDa monomer.

PMID- 10075722
TI  - Identification of a glucose response element in the promoter of the rat glucagon
      receptor gene.
AB  - We cloned the 5' upstream region of the rat glucagon receptor gene, demonstrating
      that the 5' noncoding domain of the glucagon receptor mRNA contained two
      untranslated exons of 131 and 166 nucleotides (nt), respectively, separated by
      two introns of 0.6 and 3.2 kilobase pairs. We also observed an alternative
      splicing involving the 166-base pair exon. Cloning of up to 2 kilobase pairs of
      the newly identified genomic domain and transfection of various constructs
      driving a reporter gene, in pancreatic islet cell line INS-1, uncovered a strong
      glucose regulation of the promoter activity of plasmids containing up to
      nucleotide -868, or more, upstream from the transcriptional start point. This
      promoter activity displayed threshold-like behavior, with low activity of the
      promoter below 5 mM glucose, and maximal activation as of 10 mM glucose. This
      glucose regulation was mapped to a highly palindromic 19-nucleotide region
      between nt -545 and -527. Indeed, deletion or mutation of this sequence abolished
      the glucose regulation. This domain contained two palindromic "E-boxes" CACGTG
      and CAGCTG separated by 3 nt, a feature similar to the "L4 box" found in the
      pyruvate kinase L gene promoter. This is the first description of a G protein
      coupled receptor gene promoter regulated by glucose.

PMID- 10075723
TI  - Antisense oligonucleotides containing modified bases inhibit in vitro translation
      of Leishmania amazonensis mRNAs by invading the mini-exon hairpin.
AB  - Complementary oligodeoxynucleotides (ODNs) that contain 2-aminoadenine and 2
      thiothymine interact weakly with each other but form stable hybrids with
      unmodified complements. These selectively binding complementary (SBC) agents can
      invade duplex DNA and hybridize to each strand (Kutyavin, I. V., Rhinehart, R.
      L., Lukhtanov, E. A., Gorn, V. V., Meyer, R. B., and Gamper, H. B. (1996)
      Biochemistry 35, 11170-11176). Antisense ODNs with similar properties should be
      less encumbered by RNA secondary structure. Here we show that SBC ODNs strand
      invade a hairpin in the mini-exon RNA of Leishmania amazonensis and that the
      resulting heteroduplexes are substrates for Escherichia coli RNase H. SBC ODNs
      either with phosphodiester or phosphorothioate backbones form more stable hybrids
      with RNA than normal base (NB) ODNs. Optimal binding was observed when the entire
      hairpin sequence was targeted. Translation of L. amazonensis mRNA in a cell-free
      extract was more efficiently inhibited by SBC ODNs complementary to the mini-exon
      hairpin than by the corresponding NB ODNs. Nonspecific protein binding in the
      cell-free extract by phosphorothioate SBC ODNs rendered them ineffective as
      antisense agents in vitro. SBC phosphorothioate ODNs displayed a modest but
      significant improvement of leishmanicidal properties compared with NB
      phosphorothioate ODNs.

PMID- 10075724
TI  - Sorting of furin at the trans-Golgi network. Interaction of the cytoplasmic tail
      sorting signals with AP-1 Golgi-specific assembly proteins.
AB  - The eukaryotic subtilisin-like endoprotease furin is found predominantly in the
      trans-Golgi network (TGN) and cycles between this compartment, the cell surface,
      and the endosomes. There is experimental evidence for endocytosis from the plasma
      membrane and transport from endosomes to the TGN, but direct exit from the TGN to
      endosomes via clathrin-coated vesicles has only been discussed but not directly
      shown so far. Here we present data showing that expression of furin promotes the
      first step of clathrin-coat assembly at the TGN, the recruitment of the Golgi
      specific assembly protein AP-1 on Golgi membranes. Further, we report that furin
      indeed is present in isolated clathrin-coated vesicles. Packaging into clathrin
      coated vesicles requires signal components in the furin cytoplasmic domain which
      can be recognized by AP-1 assembly proteins. We found that besides depending on
      the phosphorylation state of a casein kinase II site, interaction of the furin
      tail with AP-1 and its mu1subunit is mediated by a tyrosine motif and to less
      extent by a leucine-isoleucine signal, whereas a monophenylalanine motif is only
      involved in binding to the intact AP-1 complex. This study implies that high
      affinity interaction of AP-1 or mu1 with the cytoplasmic tail of furin needs a
      complex interplay of signal components rather than one distinct signal.

PMID- 10075725
TI  - Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c
      Jun N-terminal kinase (JNK)-dependent and -independent pathways in ovarian cancer
      cells.
AB  - The antineoplastic agent paclitaxel (TaxolTM), a microtubule stabilizing agent,
      is known to arrest cells at the G2/M phase of the cell cycle and induce
      apoptosis. We and others have recently demonstrated that paclitaxel also
      activates the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK)
      signal transduction pathway in various human cell types, however, no clear role
      has been established for JNK/SAPK in paclitaxel-induced apoptosis. To further
      examine the role of JNK/SAPK signaling cascades in apoptosis resulting from
      microtubular dysfunction induced by paclitaxel, we have coexpressed dominant
      negative (dn) mutants of signaling proteins of the JNK/SAPK pathway (Ras, ASK1,
      Rac, JNKK, and JNK) in human ovarian cancer cells with a selectable marker to
      analyze the apoptotic characteristics of cells expressing dn vectors following
      exposure to paclitaxel. Expression of these dn signaling proteins had no effect
      on Bcl-2 phosphorylation, yet inhibited apoptotic changes induced by paclitaxel
      up to 16 h after treatment. Coexpression of these dn signaling proteins had no
      protective effect after 48 h of paclitaxel treatment. Our data indicate that: (i)
      activated JNK/SAPK acts upstream of membrane changes and caspase-3 activation in
      paclitaxel-initiated apoptotic pathways, independently of cell cycle stage, (ii)
      activated JNK/SAPK is not responsible for paclitaxel-induced phosphorylation of
      Bcl-2, and (iii) apoptosis resulting from microtubule damage may comprise
      multiple mechanisms, including a JNK/SAPK-dependent early phase and a JNK/SAPK
      independent late phase.

PMID- 10075726
TI  - beta-subunit assembly is essential for the correct packing and the stable
      membrane insertion of the H,K-ATPase alpha-subunit.
AB  - The alpha-subunits of H,K-ATPase (HKAalpha) and Na,K-ATPase require a beta
      subunit for maturation. We investigated the role of the beta-subunit in the
      membrane insertion and stability of the HKAalpha expressed in Xenopus oocytes.
      Individual membrane segments M1, M2, M3, M4, and M9 linked to a glycosylation
      reporter act as signal anchor (SA) motifs, and M10 acts as a partial stop
      transfer motif. In combined HKAalpha constructs, M2 acts as an efficient stop
      transfer sequence, and M3 acts as a SA sequence. However, M5 and M9 have only
      partial SA function, and M7 has no SA function. Consistent with the membrane
      insertion properties of segments in combined alpha constructs, M1-3 alpha
      proteins are resistant to cellular degradation, and M1-5 up to M1-10 alpha
      proteins are not resistant to cellular degradation. However, co-expression with
      beta-subunits increases the membrane insertion of M9 in a M1-9 alpha-protein and
      completely protects M1-10 alpha-proteins against cellular degradation. Our
      results indicate that HKAalpha N-terminal (M1-M4) membrane insertion and
      stabilization are mediated by intrinsic molecular characteristics; however, the C
      terminal (M5-M10) membrane insertion and thus the stabilization of the entire
      alpha-subunit depend on intramolecular and intermolecular beta-subunit
      interactions that are similar but not identical to data obtained for the Na,K
      ATPase alpha-subunit.

PMID- 10075727
TI  - Characterization of a novel rat brain glycosylphosphatidylinositol-anchored
      protein (Kilon), a member of the IgLON cell adhesion molecule family.
AB  - In the central nervous system, many cell adhesion molecules are known to
      participate in the establishment and remodeling of the neural circuit. Some of
      the cell adhesion molecules are known to be anchored to the membrane by the
      glycosylphosphatidylinositol (GPI) inserted to their C termini, and many GPI
      anchored proteins are known to be localized in a Triton-insoluble membrane
      fraction of low density or so-called "raft." In this study, we surveyed the GPI
      anchored proteins in the Triton-insoluble low density fraction from 2-week-old
      rat brain by solubilization with phosphatidylinositol-specific phospholipase C.
      By Western blotting and partial peptide sequencing after the deglycosylation with
      peptide N-glycosidase F, the presence of Thy-1, F3/contactin, and T-cadherin was
      shown. In addition, one of the major proteins, having an apparent molecular mass
      of 36 kDa after the peptide N-glycosidase F digestion, was found to be a novel
      protein. The result of cDNA cloning showed that the protein is an immunoglobulin
      superfamily member with three C2 domains and has six putative glycosylation
      sites. Since this protein shows high sequence similarity to IgLON family members
      including LAMP, OBCAM, neurotrimin, CEPU-1, AvGP50, and GP55, we termed this
      protein Kilon (a kindred of IgLON). Kilon-specific monoclonal antibodies were
      produced, and Western blotting analysis showed that expression of Kilon is
      restricted to brain, and Kilon has an apparent molecular mass of 46 kDa in SDS
      polyacrylamide gel electrophoresis in its expressed form. In brain, the
      expression of Kilon is already detected in E16 stage, and its level gradually
      increases during development. Kilon immunostaining was observed in the cerebral
      cortex and hippocampus, in which the strongly stained puncta were observed on
      dendrites and soma of pyramidal neurons.

PMID- 10075728
TI  - Context-dependent transcriptional cooperation mediated by cardiac transcription
      factors Csx/Nkx-2.5 and GATA-4.
AB  - Although the cardiac homeobox gene Csx/Nkx-2.5 is essential for normal heart
      development, little is known about its regulatory mechanisms. In a search for the
      downstream target genes of Csx/Nkx-2. 5, we found that the atrial natriuretic
      peptide (ANP) gene promoter was strongly transactivated by Csx/Nkx-2.5. Deletion
      and mutational analyses of the ANP promoter revealed that the Csx/Nkx-2.5-binding
      element (NKE2) located at -240 was required for high level transactivation by
      Csx/Nkx-2.5. We also found that Csx/Nkx-2.5 and GATA-4 displayed synergistic
      transcriptional activation of the ANP promoter, and in contrast to previous
      reports (Durocher, D., Charron, F., Warren, R., Schwartz, R. J., and Nemer, M.
      (1997) EMBO J. 16, 5687-5696; Lee, Y., Shioi, T., Kasahara, H., Jobe, S. M.,
      Wiese, R. J., Markham, B., and Izumo, S (1998) Mol. Cell. Biol. 18, 3120-3129),
      this synergism was dependent on binding of Csx/Nkx-2.5 to NKE2, but not on GATA-4
      DNA interactions. Although GATA-4 also potentiated the Csx/Nkx-2.5-induced
      transactivation of the artificial promoter that contains multimerized Csx/Nkx-2.5
      binding sites, Csx/Nkx-2.5 reduced the GATA-4-induced transactivation of the GATA
      4-dependent promoters. These findings indicate that the cooperative
      transcriptional regulation mediated by Csx/Nkx-2.5 and GATA-4 is promoter context
      dependent and suggest that the complex cis-trans interactions may fine-tune gene
      expression in cardiac myocytes.

PMID- 10075729
TI  - Characterization of the transmembrane molecular architecture of the dystroglycan
      complex in schwann cells.
AB  - We have demonstrated previously 1) that the dystroglycan complex, but not the
      sarcoglycan complex, is expressed in peripheral nerve, and 2) that alpha
      dystroglycan is an extracellular laminin-2-binding protein anchored to beta
      dystroglycan in the Schwann cell membrane. In the present study, we investigated
      the transmembrane molecular architecture of the dystroglycan complex in Schwann
      cells. The cytoplasmic domain of beta-dystroglycan was co-localized with Dp116,
      the Schwann cell-specific isoform of dystrophin, in the abaxonal Schwann cell
      cytoplasm adjacent to the outer membrane. beta-dystroglycan bound to Dp116 mainly
      via the 15 C-terminal amino acids of its cytoplasmic domain, but these amino
      acids were not solely responsible for the interaction of these two proteins.
      Interestingly, the beta-dystroglycan-precipitating antibody precipitated only a
      small fraction of alpha-dystroglycan and did not precipitate laminin and Dp116
      from the peripheral nerve extracts. Our results indicate 1) that Dp116 is a
      component of the submembranous cytoskeletal system that anchors the dystroglycan
      complex in Schwann cells, and 2) that the dystroglycan complex in Schwann cells
      is fragile compared with that in striated muscle cells. We propose that this
      fragility may be attributable to the absence of the sarcoglycan complex in
      Schwann cells.

PMID- 10075730
TI  - Recycling of apolipoprotein E in mouse liver.
AB  - Following the internalization of low density lipoprotein (LDL) by the LDL
      receptor within cells, both the lipid and the protein components of LDL are
      completely degraded within the lysosomes. Remnant lipoproteins are also
      internalized by cells via the LDL receptor as well as other receptors, but the
      events following the internalization of these complexes, which use apolipoprotein
      E (apoE) as their ligand for receptor capture, have not been defined. There is
      evidence that apoE-containing beta-very low density lipoproteins follow
      differential intracellular routing depending on their size and apoE content and
      that apoE internalized with lipoproteins can be resecreted by cultured
      hepatocytes and fibroblasts. In the present studies, we addressed the question of
      apoE sparing or recycling as a physiologic phenomenon. Remnant lipoproteins (d <
      1.019 g/ml) from normal mouse plasma were iodinated and injected into normal
      C57BL/6 mice. Livers were collected at 10, 30, 60, and 120 min after injection,
      and hepatic Golgi fractions were prepared for gel electrophoresis analysis. Golgi
      preparations were analyzed for galactosyltransferase enrichment (>40-fold above
      cell homogenate) and by appearance of the Golgi stacks and vesicles on electron
      microscopy. Iodinated apoE was consistently found in the Golgi fractions peaking
      at 10 min and disappearing by 2 h after injection. Although traces of apoB48 were
      present in the Golgi fractions, the apoE/apoB ratio in the Golgi was 50-fold
      higher compared with serum. Quantitatively similar results were obtained when the
      very low density lipoprotein remnants were injected into mice deficient in either
      apoE or the LDL receptor, indicating that the phenomenon of apoE recycling is not
      influenced by the production of endogenous apoE and is not dependent on the
      presence of LDL receptors. In addition, radioactive apoE in the Golgi fractions
      was part of d = 1.019-1.21 g/ml complexes, indicating an association of recycled
      apoE with either newly formed lipoproteins or the internalized complexes. These
      studies show that apoE recycling is a physiologic phenomenon in vivo and
      establish the presence of a unique pathway of intracellular processing of apoE
      containing remnant lipoproteins.

PMID- 10075731
TI  - L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells.
AB  - Ascorbic acid has been shown to enhance impaired endothelium-dependent
      vasodilation in patients with atherosclerosis by a mechanism that is thought to
      involve protection of nitric oxide (NO) from inactivation by free oxygen
      radicals. The present study in human endothelial cells from umbilical veins and
      coronary arteries investigates whether L-ascorbic acid additionally affects
      cellular NO synthesis. Endothelial cells were incubated for 24 h with 0.1-100
      microM ascorbic acid and were subsequently stimulated for 15 min with ionomycin
      (2 microM) or thrombin (1 unit/ml) in the absence of extracellular ascorbate.
      Ascorbate pretreatment led to a 3-fold increase of the cellular production of NO
      measured as the formation of its co-product citrulline and as the accumulation of
      its effector molecule cGMP. The effect was saturated at 100 microM and followed a
      similar kinetics as seen for the uptake of ascorbate into the cells. The
      investigation of the precursor molecule L-gulonolactone and of different ascorbic
      acid derivatives suggests that the enediol structure of ascorbate is essential
      for its effect on NO synthesis. Ascorbic acid did not induce the expression of
      the NO synthase (NOS) protein nor enhance the uptake of the NOS substrate L
      arginine into endothelial cells. The ascorbic acid effect was minimal when the
      citrulline formation was measured in cell lysates from ascorbate-pretreated cells
      in the presence of known cofactors for NOS activity. However, when the cofactor
      tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of
      ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that
      ascorbic acid may either enhance the availability of tetrahydrobiopterin or
      increase its affinity for the endothelial NOS. Our data suggest that
      intracellular ascorbic acid enhances NO synthesis in endothelial cells and that
      this may explain, in part, the beneficial vascular effects of ascorbic acid.

PMID- 10075732
TI  - Reduced capacitative calcium entry correlates with vesicle accumulation and
      apoptosis.
AB  - A preneoplastic variant of Syrian hamster embryo cells, sup(+), exhibits
      decreased endoplasmic reticulum calcium levels and subsequently undergoes
      apoptosis in low serum conditions (Preston, G. A., Barrett, J. C., Biermann, J.
      A., and Murphy, E. (1997) Cancer Res. 57, 537-542). This decrease in endoplasmic
      reticulum calcium appears to be due, at least in part, to reduced capacitative
      calcium entry at the plasma membrane. Thus we investigated whether inhibition of
      capacitative calcium entry per se could reduce endoplasmic reticulum calcium and
      induce apoptosis of cells. We find that treatment with either SKF96365 (30-100
      microM) or cell-impermeant 1,2-bis(o-amino-5-bromophenoxy)ethane-N,N,N', N'
      tetraacetic acid (5-10 mM) is able to induce apoptosis of cells in conditions
      where apoptosis does not normally occur. Because previous work has implicated
      vesicular trafficking as a mechanism of regulating capacitative calcium entry, we
      investigated whether disruption of vesicular trafficking could lead to decreased
      capacitative calcium entry and subsequent apoptosis of cells. Coincident with low
      serum-induced apoptosis, we observed an accumulation of vesicles within the cell,
      suggesting deregulated vesicle trafficking. Treatment of cells with bafilomycin
      (30-100 nM), an inhibitor of the endosomal proton ATPase, produced an
      accumulation of vesicles, decreased capacitative entry, and induced apoptosis.
      These data suggest that deregulation of vesicular transport results in reduced
      capacitative calcium entry which in turn results in apoptosis.

PMID- 10075733
TI  - Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the
      photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt
      disease.
AB  - Many substrates for P-glycoprotein, an ABC transporter that mediates multidrug
      resistance in mammalian cells, have been shown to stimulate its ATPase activity
      in vitro. In the present study, we used this property as a criterion to search
      for natural and artificial substrates and/or allosteric regulators of ABCR, the
      rod photoreceptor-specific ABC transporter responsible for Stargardt disease, an
      early onset macular degeneration. ABCR was immunoaffinity purified to apparent
      homogeneity from bovine rod outer segments and reconstituted into liposomes. All
      trans-retinal, a candidate ligand, stimulates the ATPase activity of ABCR 3-4
      fold, with a half-maximal effect at 10-15 microM. 11-cis- and 13-cis-retinal show
      similar activity. All-trans-retinal stimulates the ATPase activity of ABCR with
      Michaelis-Menten behavior indicative of simple noncooperative binding that is
      associated with a rate-limiting enzyme-substrate intermediate in the pathway of
      ATP hydrolysis. Among 37 structurally diverse non-retinoid compounds, including
      nine previously characterized substrates or sensitizers of P-glycoprotein, only
      four show significant ATPase stimulation when tested at 20 microM. The dose
      response curves of these four compounds are indicative of multiple binding sites
      and/or modes of interaction with ABCR. Two of these compounds, amiodarone and
      digitonin, can act synergistically with all-trans-retinal, implying that they
      interact with a site or sites on ABCR different from the one with which all-trans
      retinal interacts. Unlike retinal, amiodarone appears to interact with both free
      and ATP-bound ABCR. Together with clinical observations on Stargardt disease and
      the localization of ABCR to rod outer segment disc membranes, these data suggest
      that retinoids, and most likely retinal, are the natural substrates for transport
      by ABCR in rod outer segments. These observations have significant implications
      for understanding the visual cycle and the pathogenesis of Stargardt disease and
      for the identification of compounds that could modify the natural history of
      Stargardt disease or other retinopathies associated with impaired ABCR function.

PMID- 10075734
TI  - A 5-kilobase pair promoter fragment of the murine epididymal retinoic acid
      binding protein gene drives the tissue-specific, cell-specific, and androgen
      regulated expression of a foreign gene in the epididymis of transgenic mice.
AB  - The murine epididymis synthesizes and secretes a retinoic acid-binding protein
      (mE-RABP) that belongs to the lipocalin superfamily. The gene encoding mE-RABP is
      specifically expressed in the mouse mid/distal caput epididymidis under androgen
      control. In transgenic mice, a 5-kilobase pair (kb) promoter fragment, but not a
      0.6-kb fragment, of the mE-RABP gene driving the chloramphenicol
      acetyltransferase (CAT) reporter gene restricted high level of transgene
      expression to the caput epididymidis. No transgene expression was detected in any
      other male or female tissues. Immunolocalization of the CAT protein and in situ
      hybridization of the corresponding CAT mRNA indicated that transgene expression
      occurred in the principal cells of the mid/distal caput epididymidis, thereby
      mimicking the spatial endogenous mE-RABP gene expression. Transgene and mE-RABP
      gene expression was detected from 30 days and progressively increased until 60
      days of age. Castration, efferent duct ligation, and hormone replacement studies
      demonstrated that transgene expression was specifically regulated by androgen but
      not by any other testicular factors. Altogether, our results demonstrate that the
      5-kb promoter fragment of the mE-RABP gene contains all of the information
      required for the hormonal regulation and the spatial and temporal expression of
      the mE-RABP gene in the epididymis.

PMID- 10075735
TI  - The essential role of Saccharomyces cerevisiae CDC6 nucleotide-binding site in
      cell growth, DNA synthesis, and Orc1 association.
AB  - Saccharomyces cerevisiae Cdc6 is a protein required for the initiation of DNA
      replication. The biochemical function of the protein is unknown, but the primary
      sequence contains motifs characteristic of nucleotide-binding sites. To study the
      requirement of the nucleotide-binding site for the essential function of Cdc6, we
      have changed the conserved Lys114 at the nucleotide-binding site to five other
      amino acid residues. We have used these mutants to investigate in vivo roles of
      the conserved lysine in the growth rate of transformant cells and the
      complementation of cdc6 temperature-sensitive mutant cells. Our results suggest
      that replacement of Lys with Glu (K114E) and Pro (K114P) leads to loss-of
      function in supporting cell growth, replacement of the Lys with Gln (K114Q) or
      Leu (K114L) yields partially functional proteins, and replacement with Arg yields
      a phenotype equivalent to wild-type, a silent mutation. To investigate what leads
      to the growth defects derived from the mutations at the nucleotide-binding site,
      we evaluated its gene functions in DNA replication by the assays of the plasmid
      stability and chromosomal DNA synthesis. Indeed, the K114P and K114E mutants
      showed the complete retraction of DNA synthesis. In order to test its effect on
      the G1/S transition of the cell cycle, we have carried out the temporal and
      spatial studies of yeast replication complex. To do this, yeast chromatin
      fractions from synchronized culture were prepared to detect the Mcm5 loading onto
      the chromatin in the presence of the wild-type Cdc6 or mutant cdc6(K114E)
      proteins. We found that cdc6(K114E) is defective in the association with
      chromatin and in the loading of Mcm5 onto chromatin origins. To further
      investigate the molecular mechanism of nucleotide-binding function, we have
      demonstrated that the Cdc6 protein associates with Orc1 in vitro and in vivo.
      Intriguingly, the interaction between Orc1 and Cdc6 is disrupted when the
      cdc6(K114E) protein is used. Our results suggest that a proper molecular
      interaction between Orc1 and Cdc6 depends on the functional ATP-binding of Cdc6,
      which may be a prerequisite step to assemble the operational replicative complex
      at the G1/S transition.

PMID- 10075736
TI  - A novel MDMX transcript expressed in a variety of transformed cell lines encodes
      a truncated protein with potent p53 repressive activity.
AB  - The MDMX gene product is related to the MDM2 oncoprotein, both of which interact
      with the p53 tumor suppressor. We have identified a novel transcript of the MDMX
      gene that is expressed in a variety of cell lines, and in particular, in growing
      and transformed cells. This transcript is identical to the published sequence yet
      it has a short internal deletion of 68 base pairs. This deletion produces a shift
      in the reading frame after codon 114, resulting in the inclusion of a stop codon
      at amino acid residue 127 (full-length MDMX is 489 residues). This truncated MDMX
      protein is termed MDMX-S ("short form"), represents only the p53-binding domain,
      and appears to bind p53 better than full-length MDMX. The MDMX-S protein can be
      detected in cell extracts and when overexpressed is much more effective than MDMX
      at inhibiting p53-mediated transcriptional activation and induction of apoptosis.
      Since MDMX-S lacks the central and carboxyl-terminal regions contained within
      full-length MDMX, it is likely to play a key role in the regulation of cell
      proliferation and apoptosis in a way distinct from MDMX.

PMID- 10075737
TI  - Caspase-dependent activation of calpain during drug-induced apoptosis.
AB  - We have previously demonstrated that calpain is responsible for the cleavage of
      Bax, a proapoptotic protein, during drug-induced apoptosis of HL-60 cells (Wood,
      D. E., Thomas, A., Devi, L. A., Berman, Y., Beavis, R. C., Reed, J. C., and
      Newcomb, E. W. (1998) Oncogene 17, 1069-1078). Here we show the sequential
      activation of caspases and calpain during drug-induced apoptosis of HL-60 cells.
      Time course experiments using the topoisomerase I inhibitor 9-amino-20(S)
      camptothecin revealed that cleavage of caspase-3 substrates poly(ADP-ribose)
      polymerase (PARP) and the retinoblastoma protein as well as DNA fragmentation
      occurred several hours before calpain activation and Bax cleavage. Pretreatment
      with the calpain inhibitor calpeptin blocked calpain activation and Bax cleavage
      but did not inhibit PARP cleavage, DNA fragmentation, or 9-amino-20(S)
      camptothecin-induced morphological changes and cell death. Pretreatment with the
      pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD
      fmk) inhibited PARP cleavage, DNA fragmentation, calpain activation, and Bax
      cleavage and increased cell survival by 40%. Interestingly, Z-VAD-fmk-treated
      cells died in a caspase- and calpain-independent manner that appeared
      morphologically distinct from apoptosis. Our results suggest that excessive or
      uncontrolled calpain activity may play a role downstream of and distinct from
      caspases in the degradation phase of apoptosis.

PMID- 10075738
TI  - Cloning and characterization of androgen receptor coactivator, ARA55, in human
      prostate.
AB  - Androgen receptor (AR) is a hormone-activated transcriptional factor that can
      bind to androgen response elements and that regulates the transcription of target
      genes via a mechanism that presumably involves cofactors. We report here the
      cloning of a novel AR coactivator ARA55 using a yeast two-hybrid system. ARA55
      consists of 444 amino acids with the predicted molecular mass of 55 kDa and its
      sequence shows very high homology to mouse hic5, a TGF-beta1-inducible gene.
      Yeast and mammalian two-hybrid systems and co-immunoprecipitation assays all
      prove ARA55 can bind to AR in a ligand-dependent manner. Transient transfection
      assay in prostate cancer DU145 cells further demonstrates that ARA55 can enhance
      AR transcriptional activity in the presence of 1 nM dihydrotestosterone or its
      antagonists such as 100 nM 17beta-estradiol or 1 microM hydroxyflutamide. Our
      data also suggest the C-terminal half of ARA55, which includes three LIM motifs,
      is sufficient to interact with AR. Northern blot and polymerase chain reaction
      quantitation showed ARA55 can be expressed differently in normal prostate and
      prostate tumor cells. Together, our data suggests that ARA55 may play very
      important roles in the progression of prostate cancer by the modulation of AR
      transactivation.

PMID- 10075739
TI  - Negative regulation by the Bacillus subtilis GerE protein.
AB  - GerE is a transcription factor produced in the mother cell compartment of
      sporulating Bacillus subtilis. It is a critical regulator of cot genes encoding
      proteins that form the spore coat late in development. Most cot genes, and the
      gerE gene, are transcribed by sigmaK RNA polymerase. Previously, it was shown
      that the GerE protein inhibits transcription in vitro of the sigK gene encoding
      sigmaK. Here, we show that GerE binds near the sigK transcriptional start site,
      to act as a repressor. A sigK-lacZ fusion containing the GerE-binding site in the
      promoter region was expressed at a 2-fold lower level during sporulation of wild
      type cells than gerE mutant cells. Likewise, the level of SigK protein (i. e. pro
      sigmaK and sigmaK) was lower in sporulating wild-type cells than in a gerE
      mutant. These results demonstrate that sigmaK-dependent transcription of gerE
      initiates a negative feedback loop in which GerE acts as a repressor to limit
      production of sigmaK. In addition, GerE directly represses transcription of
      particular cot genes. We show that GerE binds to two sites that span the -35
      region of the cotD promoter. A low level of GerE activated transcription of cotD
      by sigmaK RNA polymerase in vitro, but a higher level of GerE repressed cotD
      transcription. The upstream GerE-binding site was required for activation but not
      for repression. These results suggest that a rising level of GerE in sporulating
      cells may first activate cotD transcription from the upstream site then repress
      transcription as the downstream site becomes occupied. Negative regulation by
      GerE, in addition to its positive effects on transcription, presumably ensures
      that sigmaK and spore coat proteins are synthesized at optimal levels to produce
      a germination-competent spore.

PMID- 10075740
TI  - Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells.
AB  - The formation of prostaglandins requires the catalytic activity of cyclooxygenase
      (COX) which converts arachidonic acid to the prostaglandin endoperoxide PGH2,
      from which all other prostaglandins are formed. COX-2 is the highly inducible
      isozyme of COX which is responsible for much of the prostaglandin production in
      inflammation and is a key factor in colon carcinogenesis. Because COX-2 activity
      can be rate-limiting in prostaglandin formation, COX-2 expression must be
      regulated tightly. Numerous factors, including mitogens, tumor promoters, and
      cytokines have been found to stimulate the transcription of COX-2. We show that
      fatty acids, prostaglandins, and non-steroidal anti-inflammatory drugs, compounds
      that are substrates, products, and inhibitors, respectively, of COX enzymatic
      activity, also increase its expression. These compounds are members of a
      heterogeneous group of compounds known as peroxisome proliferators, and the
      prototypical peroxisome proliferator, WY-14, 643, also enhanced COX-2 expression.
      We demonstrate that these compounds increase COX-2 transcription, and we identify
      a region of the COX-2 promoter containing a peroxisome proliferator response
      element that is responsible for the enhancement of COX-2 expression seen with
      these compounds.

PMID- 10075741
TI  - c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845
      and Tyr1101 is associated with modulation of receptor function.
AB  - Accumulating evidence indicates that interactions between the epidermal growth
      factor receptor (EGFR) and the nonreceptor tyrosine kinase c-Src may contribute
      to an aggressive phenotype in multiple human tumors. Previous work from our
      laboratory demonstrated that murine fibroblasts which overexpress both these
      tyrosine kinases display synergistic increases in DNA synthesis, soft agar
      growth, and tumor formation in nude mice, and increased phosphorylation of the
      receptor substrates Shc and phospholipase gamma as compared with single
      overexpressors. These parameters correlated with the ability of c-Src and EGFR to
      form an EGF-dependent heterocomplex in vivo. Here we provide evidence that
      association between c-Src and EGFR can occur directly, as shown by receptor
      overlay experiments, and that it results in the appearance of two novel tyrosine
      phosphorylations on the receptor that are seen both in vitro and in vivo
      following EGF stimulation. Edman degradation analyses and co-migration of
      synthetic peptides with EGFR-derived tryptic phosphopeptides identify these sites
      as Tyr845 and Tyr1101. Tyr1101 lies within the carboxyl-terminal region of the
      EGFR among sites of receptor autophosphorylation, while Tyr845 resides in the
      catalytic domain, in a position analogous to Tyr416 of c-Src. Phosphorylation of
      Tyr416 and homologous residues in other tyrosine kinase receptors has been shown
      to be required for or to increase catalytic activity, suggesting that c-Src can
      influence EGFR activity by mediating phosphorylation of Tyr845. Indeed, EGF
      induced phosphorylation of Tyr845 was increased in MDA468 human breast cancer
      cells engineered to overexpress c-Src as compared with parental MDA 468 cells.
      Furthermore, transient expression of a Y845F variant EGFR in murine fibroblasts
      resulted in an ablation of EGF-induced DNA synthesis to nonstimulated levels.
      Together, these data support the hypothesis that c-Src-mediated phosphorylation
      of EGFR Tyr845 is involved in regulation of receptor function, as well as in
      tumor progression.

PMID- 10075742
TI  - New bioactive flavonoids and stilbenes in cube resin insecticide.
AB  - Fractionation of cube resin from Lonchocarpus utilus and L. urucu roots led to
      the isolation and identification of 11 minor flavonoids and stilbenes containing
      the gem-dimethylpyran moiety or a dihydrodiol derivative thereof. The eight new
      compounds were as follows: the isoflavonoid cis-4'',5''-dihydro-4'',5' '
      dihydroxylonchocarpusone (2); four (2S)-6-(gamma, gamma-dimethylallyl)-6'',6''
      dimethylpyran[2'',3'':7, 8]flavanones with substituents of 5-hydroxy-3',4'
      dimethoxy (3), 5, 3'-dihydroxy-4'-methoxy (4), 5,4'-dihydroxy-3'-methoxy (5), and
      3', 4'-dimethoxy (6); and three 6'',6''-dimethylpyran[2'',3'':3', 4']stilbenes
      with 4-hydroxy-5'-methoxy (9), 3,5'-dimethoxy-4-hydroxy (10) and 3,4,5-trimethoxy
      (11) substitution patterns. Structure-activity relationships for inhibition of
      NADH:ubiquinone oxidoreductase activity (bovine heart electron transport
      particles) and phorbol ester-induced ornithine decarboxylase activity (cultured
      MCF-7 cells) generally parallel those for cytotoxicity (MCF-7 and Hepa 1clc7
      cells).

PMID- 10075743
TI  - Two new pyridine monoterpene alkaloids by chemical conversion of a commercial
      extract of harpagophytum procumbens 
AB  - The treatment of harpagide (1), harpagoside (2), or 8-O-p-coumaroylharpagide (3),
      the main iridoids of Harpagophytum procumbens and Harpagophytum zeyheri, with NH3
      and HCl led to aucubinine B(4), a pyridine monoterpene alkaloid (PMTA). A similar
      procedure applied to a commercial extract of H. procumbens yielded 4 and two new
      PMTAs named beatrine A (5) and beatrine B (6). The structures of these new PMTAs
      were established using ESIMS and 2D NMR. Their semisynthesis was analyzed in
      terms of reaction mechanisms.

PMID- 10075744
TI  - Nuapapuin A and sigmosceptrellins D and E: new norterpene cyclic peroxides from a
      southern australian marine sponge, sigmosceptrella sp 
AB  - A Sigmosceptrella sp. from the Great Australian Bight, Australia, has yielded the
      new norditerpene cyclic peroxide, nuapapuin A (2a), and the norsesterterpene
      cyclic peroxide sigmosceptrellin D (3a), characterized as the corresponding
      methyl esters 2b and 3b. The crude methylated sponge extract also yielded the new
      norsesterterpene cyclic peroxide sigmosceptrellin E methyl ester (4). Relative
      stereochemistry about C2, C3, and C6 was assigned by established empirical rules
      and absolute stereochemistry by the advanced Mosher procedure. A plausible
      biosynthetic pathway has been proposed that rationalizes key transformations in
      the biosynthesis of all known norterpene cyclic peroxides and related norterpene
      ketones, dienes and sigmosceptrins.

PMID- 10075745
TI  - Paclitaxel analogues from Taxus x media cv. Hicksii.
AB  - The roots of T. x media Rehd. cv. Hicksii gave three novel analogues of
      paclitaxel modified at the N-acyl residue (N-debenzoyl-N-alpha-methylbutyryl
      paclitaxel and N-debenzoyl-N-cinnamoyl paclitaxel, 1b and 1c, respectively) or at
      the ester group at C-2 (2-debenzoyl-2-tigloyl paclitaxel, 1d). Compounds 1b and
      1d showed reduced cytotoxicity and tubulin binding compared to paclitaxel, while
      1c retained substantial activity in these assays.

PMID- 10075746
TI  - New cytotoxic oxygenated fucosterols from the brown alga Turbinaria conoides.
AB  - Fucosterol (1), 24xi-hydroperoxy-24-vinylcholesterol (2), 29-hydroperoxystigmasta
      5,24(28)-dien-3beta-ol (3), 24-ethylcholesta-4,24(28)-dien-3-one (4), 24xi
      hydroperoxy-24-ethylcholesta-4,28(29)-dien-3-one (5), 24-ethylcholesta-4,24(28)
      dien-3,6-dione (6), 24xi-hydroperoxy-24-ethylcholesta-4,28(29)-dien-3,6-di one
      (7), 6beta-hydroxy-24-ethylcholesta-4,24(28)-dien-3-one (8), and 24xi-hydroperoxy
      6beta-hydroxy-24-ethylcholesta-4,28(2 9)-dien-3-one (9) were isolated from the
      marine brown alga Turbinaria conoides. The structures of these compounds were
      established by spectral analysis. Isolated for the first time from a natural
      source, the oxygenated fucosterols 4-9 exhibit cytotoxicity against various
      cancer cell lines.

PMID- 10075747
TI  - New triterpenoid saponins from Maesa japonica.
AB  - New triterpenoid saponins, maejaposides A, B, C, D, and E, were isolated from the
      roots of Maesa japonica and were, respectively, defined to be 3-O-[beta-D
      xylopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->2)-bet a-D-galactopyranosyl-(1
      ->3)] [beta-D-galactopyranosyl-(1-->2)]beta-D-glucuronopyranosides of 22alpha
      [(Z)-2-hexenoyloxy]-13beta,28-oxido-olean++ +-16alpha, 28alpha-diol (1); 22alpha
      [2'-methylbutanoyl]-13beta, 28-oxido-olean-16alpha,28alpha-diol (2a) and 22alpha
      angeloyloxy-13beta,28-oxido-olean-16a lpha,28alpha-diol (2b); 21beta,22alpha
      diangeloyloxy-13beta,28-oxido- olean-16alpha, 28alpha-diol (3); 21beta
      angeloyloxy, 22alpha-(2'-methylbutanoyl)-13beta,28-oxido-olean++ +-16alpha,
      28alpha-diol (4), and 21beta-angeloyloxy, 22alpha-[(Z)-2'-hexenoyl]-13beta,28
      oxido-olean- 16alpha,28alpha-diol (5). Their structures were established on the
      basis of extensive NMR (DEPT, COSY, HOHAHA, HETCOR, HMBC, and NOESY) and ESIMS/MS
      studies, along with chemical degradation.

PMID- 10075748
TI  - Five new triterpene saponins from Pulsatilla patens var. multifida.
AB  - Five new oleanane-type glycosides (1-5), along with two known triterpene
      saponins, were isolated from the roots of Pulsatilla patens var. multifida
      (Ranunculaceae). The structures of the new triterpene saponins were elucidated as
      3-O-beta-D-glucopyranosyl(1-->2)-beta-D-galactopyranosyl hederagenin 28-O-beta-D
      glucopyranosyl ester (1), hederagenin 3-O-[beta-D-glucopyranosyl(1-->2)][beta-D
      glucopyranosyl(1-->6)]-beta -D-galactopyranoside (2), 3-O-beta-D-glucopyranosyl
      bayogenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta 
      D-glucopyranosyl ester (3), 3-O-beta-D-glucopyranosyl(1-->2)-beta-D
      galactopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D
      glucopyranosyl(1-->6)-beta -D-glucopyranosyl ester (4), and 3-O-[beta-D
      glucopyranosyl(1-->2)][beta-D-glucopyranosyl(1-->6)]-beta -D-galactopyranosyl
      hederagenin 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta
      -D-glucopyranosyl ester (5). Structure elucidation was accomplished by 1D and 2D
      NMR (HMQC, HMBC, and ROESY) methods, FABMS, and hydrolysis.

PMID- 10075749
TI  - 11-Isopropylcryptolepine: A novel alkaloid isolated from cryptolepis
      sanguinolenta characterized using submicro NMR techniques 
AB  - A new alkaloid has been isolated from extracts of the West African plant
      Cryptolepis sanguinolenta and identified by submicro NMR techniques as 11
      isopropylcryptolepine (1). The unusual incorporation of the isopropyl group at
      the 11-position of the indolo[3,2-b]quinoline nucleus is suggestive of a mixed
      biosynthetic origin for the alkaloid.

PMID- 10075750
TI  - Five new flavone 5-O-glycosides from Lethedon tannaensis: lethedosides and
      lethediosides.
AB  - Five new 7-methoxy-flavone 5-O-glycosides were isolated from a cytotoxic MeOH
      extract of Lethedon tannaensis, and the structures were elucidated by 2D NMR
      spectral analysis and by chemical methods. Lethedosides A (1), B (2), and C (3)
      were 5-O-glucosides of 7,3', 4'-tri-O-methylluteolin, 7,3',4',5'-tetra-O
      methyltricetin, and 7,3', 4'-tri-O-methytricetin, respectively; lethediosides A
      (4) and B (5) and a known compound 6 were 5-O-xylosylglucosides of 7,3', 4'-tri-O
      methylluteolin, 7,3',4',5'-tetra-O-methyltricetin, and 7, 4'-di-O-methylapigenin,
      respectively. These flavonoids were either inactive or weakly active against KB
      tumor cells, in contrast to previously isolated flavones from the same plant.

PMID- 10075751
TI  - Accelerated solvent extraction of paclitaxel and related compounds from the bark
      of taxus cuspidata 
AB  - Accelerated solvent extraction (ASE) of paclitaxel and related compounds from
      Taxus cuspidata (Japanese yew) bark has been investigated under various
      conditions. In ASE, pressure is applied to the sample extraction cell to maintain
      the heated solvent in a liquid state during the extraction. This method is able
      to shorten the extraction time and to increase the recovery of target compounds.
      In this study, ASE of paclitaxel, baccatin III, and 10-deacetylbaccatin III
      produced amounts of these compounds that were higher than those from ordinary
      solvent extraction at room temperature. The conditions providing the highest
      recovery of paclitaxel were as follows: solvent, MeOH-H2O (90:10); temperature,
      150 degrees C; and pressure, 10.13 MPa (0.128% w/w recovery based on oven-dried
      sample powder). ASE does not require chlorinated solvents and can reduce solvent
      consumption because of its strong dissolving power. Moreover, with water alone,
      the recovery of paclitaxel and related compounds using ASE is much higher than
      with other extraction methods.

PMID- 10075752
TI  - Coordinated accumulation of (+)-delta-cadinene synthase mRNAs and gossypol in
      developing seeds of Gossypium hirsutum and a new member of the cad1 family from
      G. arboreum.
AB  - A new member of the (+)-delta-cadinene synthase (CAD1) family was isolated from a
      Gossypium arboreum cDNA library. This cDNA encodes a protein that showed 97.3%,
      96.9%, and 79.2% sequence identities with the proteins encoded by previously
      isolated cDNAs of cad1-C1, cad1-C14, and cad1-A, respectively. It may be grouped
      into the cad1-C subfamily as cad1-C2. Seeds of a glanded cotton cultivar, G.
      hirsutum cv. Sumian-6, were collected at different intervals during maturation,
      and the cad1 mRNA levels were analyzed by quantitative RT-PCR. The transcripts
      could be detected in seeds of 27 DPA (days postanthesis) and increased
      dramatically along with the seed maturation, which coordinated with an increase
      in sesquiterpene cyclase activities and subsequently the accumulation of
      gossypol. The transcription level detected with primers specific to cad1-C
      (including at least C1, C14, and cdn1) was higher than that detected with primers
      specific to cad1-A, and mRNA was detected also with cad1-C2-specific primers.
      This investigation indicates that, in developing seeds of the glanded cotton
      cultivar, genes of both the CAD1-C and CAD1-A subfamilies are expressed and there
      is an active biosynthesis of cadinene-type sesquiterpenes.

PMID- 10075753
TI  - Sapinofuranones A and B, two new 2(3H)-dihydrofuranones produced by sphaeropsis
      sapinea, a common pathogen of conifers 
AB  - Two new 5-substituted dihydrofuranones, named sapinofuranones A and B (1 and 2),
      were isolated from liquid cultures of Sphaeropsis sapinea, a phytopathogenic
      fungus causing a wide range of disease symptoms on conifers. A fungal strain
      isolated from Cupressus macrocarpa produced both 1 and 2 at concentrations higher
      than those produced by the strain isolated from Cupressus sempervirens. Bioassay
      of 1 and 2 gave epinasty and brown discoloration on petioles of tomato leaves,
      sapwood stain on inner cortical tissues of the stem of cypress seedlings, and
      yellowing and needle blight on pine seedlings. Compounds 1 and 2 were
      characterized, using spectroscopic and chemical methods, as two new 4-[(2Z, 4E)-1
      hydroxy-2,4-hexadienyl]butan-4-olides, which are epimers at C-1 of the side
      chain. The absolute stereochemistry of this chiral center, determined by
      application of the Mosher's method, proved to be S and R in 1 and 2,
      respectively.

PMID- 10075754
TI  - Absolute structures of new briarane diterpenoids from junceella fragilis 
AB  - Four new diterpenoids with the briarane skeleton, (-)-4-deacetyljunceellolide D
      (2), (+)-11alpha, 20alpha-epoxyjunceellolide D (3), (-)-11alpha, 20alpha-epoxy-4
      deacetyljunceellolide D (4), and (-)-11alpha, 20alpha-epoxy-4
      deacetoxyjunceellolide D (5), (+)-junceellolide A (6) [the antipodal derivative
      of the known (-)-junceellolide A], along with three known briaranes, (-)
      junceellolide D (1), (-)-junceellin (7), and (-)-praelolide (8), were isolated
      from the Indonesian gorgonian Junceella fragilis. The structures of the new
      compounds were established on the basis of extensive NMR studies and by
      comparison with the spectral data from other briarane compounds. The absolute
      configurations for four of the compounds were determined by the modified Mosher
      method and by unambiguous chemical interconversions.

PMID- 10075755
TI  - Calamistrins A and B, two new cytotoxic monotetrahydrofuran annonaceous
      acetogenins from Uvaria calamistrata.
AB  - Two new bioactive monotetrahydrofuran acetogenins, calamistrins A (1) and B (2),
      and two known compounds, uvarigrin (3) and uvarigranin (4), have been isolated
      from the roots of Uvaria calamistrata. The structures of the new compounds were
      elucidated by spectroscopic and chemical methods. The absolute stereochemistry of
      the stereogenic centers was established by Mosher ester methodology.

PMID- 10075756
TI  - Camelliols A-C, three novel incompletely cyclized triterpene alcohols from
      sasanqua oil (Camellia sasanqua) 
AB  - Three novel triterpene alcohols, camelliols A (1), B (3), and C (5), possessing a
      mono-, bi-, and tricyclic ring system, respectively, have been isolated, along
      with achilleol A, a known monocyclic triterpene alcohol, from the nonsaponifiable
      lipids of sasanqua oil (Camellia sasanqua). The structures of these new alcohols
      were determined on the basis of spectroscopic methods.

PMID- 10075757
TI  - New minor diterpenoid diacylglycerols from the skin of the nudibranch anisodoris
      fontaini 
AB  - The Patagonian dorid nudibranch Anisodoris fontaini contains in its mantle a
      series of isocopalane diterpenoid diacylglycerols. Five new minor metabolites,
      anisodorins 1-5 (1-5), along with the already reported 6 and 7, have been
      isolated and chemically characterized. The structure and the relative
      stereochemistries have been determined by spectroscopic means, while the absolute
      stereochemistries for 2-5 are suggested to be the same as for the biogenetically
      related major compounds 6 and 7. Synthesis of the enantiomer (8) of anisodorin 1
      confirmed the proposed structure and absolute stereochemistry.

PMID- 10075758
TI  - Halohydrins and polyols derived from antirrhinoside: structural revisions of
      muralioside and epimuralioside 
AB  - Treatment of the iridoid glucoside antirrhinoside (1) with pyridinium chloride in
      dimethylformamide gave rise to the two possible trans-halohydrins, linarioside
      (4) and isolinarioside (5). Pyridinium bromide gave the two analogous
      bromohydrins. It is shown that the iridoid glucosides 8-epi-muralioside from
      Linaria arcusangeli and 7,8-epi-antirrhinoside from Linaria dalmatica are both
      identical with isolinarioside, and therefore, these names are redundant. The
      structure of muralioside isolated from Cymbalaria muralis is revised to that of
      its 8-epimer (8), while the structure of an isomeric, new iridoid glucoside from
      Paulownia tomentosa has been elucidated to be 7beta-hydroxyharpagide (3), the
      structure originally assigned to 8. In addition, 7alpha-hydroxyharpagide (2), the
      known product from the base-catalyzed hydrolytic opening of 1, has been isolated
      from Antirrhinum majus and thus shown to be a natural product.

PMID- 10075759
TI  - New steroid glycosides from the deep-water starfish Mediaster murrayi.
AB  - Four new 24-O-biosides of 5alpha-cholestane-3beta,6alpha,8,15beta, 24-pentaol,
      designated as mediasterosides M1 (1), M2 (2), M3 (3), and M4 (4), and the
      previously known 5alpha-cholestane-3beta,6beta,8, 15alpha,16beta,26-hexaol (5)
      have been isolated from the deep-water starfish Mediaster murrayi. Glycosides 1-3
      contain rare carbohydrate moieties with (1-->5) bonds between the monosaccharide
      units. Compounds 1 and 2 showed the inhibition of cell division of fertilized sea
      urchin eggs and exhibited moderate hemolytic activities.

PMID- 10075760
TI  - Seven novel macrocyclic polypeptides from Viola arvensis.
AB  - Seven novel macrocyclic polypeptides, designated as varv peptides B-H, have been
      isolated from the aerial parts of Viola arvensis. Their primary structures have
      been elucidated by automated Edman degradation and mass spectrometry. They all
      consist of 29 or 30 amino acid residues, covalently cyclized via the amide
      backbone and by three internal disulfide bridges. Their amino acid sequences are
      as follows: varv peptide B, cyclo-(TCFGGTCNTPGCSCDPWPMCSRNGLPVCGE); varv peptide
      C, cyclo-(TCVGGTCNTPGCSCSWPVCTRNGVPICGE); varv peptide D, cyclo
      (TCVGGSCNTPGCSCSWPVCTRNGLPICGE); varv peptide E, cyclo
      (TCVGGTCNTPGCSCSWPVCTRNGLPICGE); varv peptide F, cyclo
      (TCTLGTCYTAGCSCSWPVCTRNGVPICGE); varv peptide G, cyclo
      (TCFGGTCNTPGCSCDPWPVCSRNGVPVCGE); and varv peptide H, cyclo
      (TCFGGTCNTPGCSCETWPVCSRNGLPVCGE). The varv peptides B-H exhibited high degrees of
      homology with the hitherto known macrocyclic peptides varv peptide A, kalata B1,
      violapeptide I, circulins A and B, and cyclopsychotride A.

PMID- 10075761
TI  - Six new spongian diterpenes from the sponge spongia matamata 
AB  - Chemical investigation of the sponge Spongia matamata collected in Yap,
      Micronesia, has resulted in the isolation of six new spongian diterpenoids, 2-7,
      along with the known compound, spongia-13(16), 14-dien-19-oic acid (1). The
      structures were determined by spectroscopic methods.

PMID- 10075762
TI  - 28-deacetylbelamcandal, a tumor-promoting triterpenoid from Iris tectorum.
AB  - A spiroiridal-type triterpenoid, 28-deacetylbelamcandal (1), was isolated from
      the rhizomes of Iris tectorum as an active principle that stimulated
      differentiation of human promyelocytic leukemia (HL-60) cells, a short-term
      screening method for 12-O-tetradecanoylphorbol 13-acetate (TPA)-type tumor
      promoters. In the same manner as TPA, compound 1 bound to protein kinase C (PKC)
      and activated PKC, and induced tumor necrosis factor-alpha release from HL-60
      cells. In an in vivo study, groups treated with 100 microg 7, 12
      dimethylbenz[a]anthracene plus 400 nmol of 1 showed 64.3% tumor incidence by week
      20. It has thus been demonstrated that 1 represents a new structural class of
      mouse skin-tumor promoters.

PMID- 10075763
TI  - Antioxidant and antiinflammatory activities of anthocyanins and their aglycon,
      cyanidin, from tart cherries.
AB  - The anthocyanins (1-3) and cyanidin isolated from tart cherries exhibited in
      vitro antioxidant and antiinflammatory activities comparable to commercial
      products. The inhibition of lipid peroxidation of anthocyanins 1-3 and their
      aglycon, cyanidin, were 39, 70, 75, and 57%, respectively, at 2-mM
      concentrations. The antioxidant activities of 1-3 and cyanidin were comparable to
      the antioxidant activities of tert-butylhydroquinone and butylated hydroxytoluene
      and superior to vitamin E at 2-mM concentrations. In the antiinflammatory assay,
      cyanidin gave IC50 values of 90 and 60 mM, respectively, for prostaglandin H
      endoperoxide synthase-1 and prostaglandin H endoperoxide synthase-2 enzymes.

PMID- 10075764
TI  - Two diterpenoids from the roots of gaultheria yunnanensis 
AB  - Two new diterpenoids, gaultheric acid (1) and gaultheronoterpene (2), were
      isolated from the roots ofGaultheria yunnanensis. Their structures were
      elucidated as 12-hydroxy-13-acetyl-8,11, 13-podocarpatrien-18-oic acid (1) and
      3beta, 12-dihydroxy-13-acetyl-4(18),8,11,13-podocarpatetraene (2) on the basis of
      spectral analysis.

PMID- 10075765
TI  - A new pregnane glycoside from Dioscorea collettii var. hypoglauca.
AB  - During further bioactivity-guided fractionation, a new pregnane glycoside,
      hypoglaucin G (1), and a known compound, pregna-5, 16-dien-3beta-ol-20-one 3-O
      alpha-L-rhamnopyranosyl-(1-->2)- [alpha-L-rhamnopyranosyl-(1-->4)] -beta-D
      glucopyranoside (2), were isolated from the EtOH extract of Dioscorea collettii
      var. hypoglauca rhizomes, which induced morphological deformation of Pyricularia
      oryzae mycelia with minimum morphological deformation concentration values of 135
      microM and 236 microM, respectively. The structure of 1 was established as 16beta
      (4'-methyl-5'-O-beta-D-glucopyranosyl- pentanoxyl)-pre gn-5-en-3 beta-ol-20-one 3
      O-alpha-L- rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-
      glucopyranoside on the basis of chemical evidence and spectral analysis,
      especially by 2D NMR techniques.

PMID- 10075766
TI  - Antitumor agents. 190. Absolute stereochemistry of the cytotoxic germacranolides,
      tomenphantins A and B, from Elephantopus tomentosus.
AB  - The structures and absolute stereochemistries of tomenphantins A (1) and B (2),
      cytotoxic germacranolides isolated from Elephantopus tomentosus, are reported
      herein. 1H and 13C NMR spectroscopic data, chemical transformation, and single
      crystal X-ray analysis were used in these determinations.

PMID- 10075767
TI  - Flavonol glycosides from cassia hirsuta 
AB  - A new flavonol glycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L
      rhamnopyranoside (1), was isolated from the flowers of Cassia hirsuta along with
      two known flavonol glycosides, kaempferol 3-O-rutinoside and rutin. The structure
      of compound 1 has been established on the basis of spectral data and by acid
      hydrolysis.

PMID- 10075769
TI  - Two new lupane-type triterpenes from diospyros maritima 
AB  - Two new lupane derivatives, 3-(E)-coumaroylbetulinaldehyde (1) and 3-(E)
      coumaroyl-28-palmitoylbetulin (2), have been isolated from the stems of Diospyros
      maritima. Their structures were determined by using spectral and chemical
      methods.

PMID- 10075768
TI  - Diterpenoids from Baccharis pingraea.
AB  - From the aerial parts of Baccharis pingraea the known furolabdane, angeloyl
      gutierrezianolic acid (1); two novel diterpenoids, furolabda-6,8-dien-17-oic acid
      (2) and furolabd-7-en-17-oic acid (3); and the known linear diterpenoid, (10E)
      centipedic acid (4), were isolated. LC/MS suggested the presence of
      gutierrezianolic acid (5). The structures of the new compounds were elucidated by
      1D and 2D NMR methods.

PMID- 10075770
TI  - A new amide from zanthoxylum armatum 
AB  - A new amide designated as armatamide (1)-along with two lignans, asarinin and
      fargesin, alpha- and beta-amyrins, lupeol, and beta-sitosterol-beta-D-glucoside
      has been isolated from the bark of Zanthoxylum armatum. The structure of the new
      compound was deduced by spectral and chemical analysis as N-(4'-methoxyphenyl
      ethyl)-3, 4-methylenedioxy cinnamoyl amide.

PMID- 10075771
TI  - Briarane diterpenes from the gorgonian octocoral erythropodium caribaeorum from
      the northern caribbean 
AB  - An investigation of the gorgonian octocoral Erythropodium caribaeorum collected
      off the north coast of Jamaica has yielded three new briarane diterpenes. In
      addition, the six known diterpenes, erythrolides A, B, D, E, F, and I were
      isolated. The structures of these diterpenes were established by 1H and 13C NMR
      spectroscopy utilizing DEPT, COSY, and HETCOR experiments.

PMID- 10075772
TI  - Okaramines H and I, new okaramine congeners, from aspergillus aculeatus 
AB  - Two new congeners of okaramine, okaramines H (3) and I (4), were isolated from
      okara fermented with Aspergillus aculeatus KF-428. Their structures were
      elucidated by spectroscopic methods. Neither okaramine H nor I showed
      insecticidal activity against silkworms.

PMID- 10075773
TI  - Norpregnane glycosides from a Thai soft coral, Scleronephthya pallida.
AB  - Two new norpregnane glycosides, 19-norpregna-1,3,5(10), 20-tetraen-3-O-alpha
      fucopyranoside (3) and 19-norpregna-1,3,5(10), 20-tetraen-3-O-beta
      arabinopyranoside (4), were isolated from the soft coral Scleronephthya pallida,
      along with two known steroids, pregna-1,20-dien-3-one (1) and 19-norpregna
      1,3,5(10), 20-tetraen-3-ol (2). 19-Norpregna-1,3,5(10), 20-tetraen-3-O-alpha
      fucopyranoside (3) exhibits moderate antimalarial and cytotoxic activities. The
      chemical structures of 1-4 were elucidated from spectroscopic data.

PMID- 10075774
TI  - 4-hydroxylated piperidines and N-methyleuphococcinine (1-methyl-3-granatanone)
      from Picea (Spruce) species. Identification and synthesis.
AB  - Three trace alkaloids from Colorado blue spruce, Picea pungens, were identified
      by synthesis and GC-MS comparisons as 4alpha-hydroxy-cis-2-methyl-6-(2
      oxopropyl)piperidine (1), 4alpha-hydroxy-cis-2-methyl-6-propylpiperidine (11),
      and 1-methylgranatanone (15) (N-methyl-9-aza-1-methylbicyclo[3.3. 1]nonane or N
      methyleuphococcinine). Alkaloids 1 and 11 are the first among numerous known pine
      and spruce piperidines to contain a ring-oxygenated substituent.

PMID- 10075775
TI  - Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1,
      from the flowers of Eucalyptus albens.
AB  - Sideroxylonal C (3), a new phloroglucinol dimer, was isolated from the flowers of
      Eucalyptus albens through bioassay-guided fractionation. The structure
      elucidation was based on 1D and 2D NMR experiments, MS analysis, and comparison
      with sideroxylonals A (1) and B (2). Sideroxylonal C inhibited human plasminogen
      activator inhibitor type-1 at 4.7 microM without any significant effect on human
      tissue plasminogen activator.

PMID- 10075776
TI  - Terpenoids of Syzygium formosanum.
AB  - A new natural product, 4-epifriedelin (1), and 12 known terpenoids have been
      isolated from the leaves of Syzygium formosanum. The known compounds include
      caryophyllene oxide, friedelin, canophyllal, glutinol, alpha-terpineol, phytol,
      betulinic acid, uvaol, lupeol, betulin, ursolic acid, and oleanolic acid. All of
      these compounds are reported for the first time from S. formosanum.

PMID- 10075777
TI  - Antimalarial activity of macrocyclic trichothecenes isolated from the fungus
      Myrothecium verrucaria.
AB  - Bioassay-guided fractionation of an extract from the fungus Myrothecium
      verrucaria BCC 112 resulted in the first isolation of roridin E acetate (5) from
      nature together with four common macrocyclic trichothecene isomers (1-4).
      Trichothecenes 1-5, while known as mycotoxins, were evaluated for their high
      antimalarial activity.

PMID- 10075778
TI  - New jaspamide derivatives from the marine sponge Jaspis splendans collected in
      Vanuatu.
AB  - Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated
      from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical
      structures were determined from 1D and 2D NMR studies and MS data. These two
      compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines
      with IC50 values in the microg/mL range.

PMID- 10075779
TI  - Nordihydrocapsiate, a new capsinoid from the fruits of a nonpungent pepper,
      capsicum annuum 
AB  - A new capsiate-like substance, named nordihydrocapsiate (1), has been isolated
      from the fruits of a nonpungent cultivar, CH-19 Sweet, of pepper (Capsicum
      annuum). The structure of 1 was determined to be 4-hydroxy-3-methoxybenzyl 7
      methyloctanoate by spectroscopic methods.

PMID- 10075780
TI  - Chemical conversion of vibsanin C to vibsanin E and structure of 3
      hydroxyvibsanin E from viburnum awabuki 
AB  - Vibsanin E (4), a tricyclic vibsane-type diterpene, has been prepared in 50%
      yield from vibsanin C (2), a seven-membered ring vibsane-type diterpene by
      reaction with BF3.OEt2 at -78 degrees C. This chemical correlation not only
      established structure, including absolute configurations, but also has
      demonstrated a possible biosynthetic route to 4 via 2 derived from vibsanin B
      (1). The structure of 3-hydroxyvibsanin E (5), another example of a tricyclic
      seven-membered ring vibsane, isolated from the leaves of Viburnumawabuki, has
      been established by extensive analyses of 2D NMR data and comparison of its
      spectral data with those of 4.

PMID- 10075781
TI  - Cyclic hemiacetals with seven-membered rings from an undescribed SalaciaSpecies
      from monteverde, costa rica 
AB  - The two cyclic hemiacetals of 30-hydroxyfriedelan-3-on-28-al (1R and 1S) were
      found in an undescribed Salacia species from Costa Rica and characterized by
      spectral methods.

PMID- 10075782
TI  - Verbaspinoside, a new iridoid glycoside from Verbascum spinosum.
AB  - A new iridoid glycoside, verbaspinoside (1), was isolated from the aerial parts
      of Verbascum spinosum. Its structure was elucidated on the basis of chemical and
      spectral data as 6-O-[(2' '-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]-catalpol.
      Additionally, three known iridoids (aucubin, catalpol, and ajugol) and three
      phenylpropanoid glycosides [acteoside, angoroside A (2), and angoroside C (3)]
      were isolated and identified.

PMID- 10075783
TI  - Maprouneacin, a new daphnane diterpenoid with potent antihyperglycemic activity
      from Maprounea africana.
AB  - Bioassay-guided fractionation of the EtOH extract of M. africana, using the in
      vivo noninsulin-dependent diabetes mellitus db/db mouse model, resulted in the
      isolation of the new daphnane-type diterpenoid maprouneacin (2). Compound 2
      showed potent glucose-lowering properties when given by the oral route.

PMID- 10075784
TI  - Four aristolochic acid esters of rearranged ent-elemane sesquiterpenes from
      aristolochia heterophylla 
AB  - Four aristolochic acid esters of ent-elemane type sesquiterpene having a new
      carbon skeleton, aristophyllides A (1), B (2), C (3), and D (4), were isolated
      from the stems and roots of Aristolochia heterophylla. The esters were
      characterized by NMR and MS methods and included is a study of absolute
      configurations using the CD exciton chirality method.

PMID- 10075785
TI  - New marine prostanoids from the okinawan soft coral, clavularia viridis 
AB  - Two new marine prostanoids-17,18-dehydroclavulone I (1) and clavulolactone I (2)
      were isolated from the Okinawan soft coral, Clavularia viridis. Their structures,
      including absolute configurations, were determined based on the results of
      spectroscopic analysis and chemical conversions.

PMID- 10075786
TI  - N-Acetyl derivatives of type C fumonisins produced by fusarium oxysporum 
AB  - Four new fumonisins, an isomer of fumonisin C1 (iso-FC1) (1) and three N-acetyl
      derivatives of hydroxylated fumonisin C1 (OH-FC1) (2), fumonisin C1 (FC1) (3),
      and iso-FC1 (4) were isolated from wheat cultures of Fusarium oxysporum. One of
      the hydroxy groups of compound 1 is at C-3 instead of C-4 for FC1. Compounds 2-4
      are similar in structure to OH-FC1, FC1, and iso-FC1, respectively, except for
      the presence of an acetyl group at the amine of C-1.

PMID- 10075787
TI  - Sphaeric acid, a new succinic acid derivative from a Sphaeropsis sp.
AB  - The structure of sphaeric acid (1), a novel succinic acid derivative isolated
      from the fermentation broth of a Sphaeropsis sp., was determined by spectral data
      and synthetic transformation to the diol of sphaeric acid and subsequently to a
      pair of gamma-lactones (2 and 3).

PMID- 10075788
TI  - Two new maytansinoids from maytenus buchananii 
AB  - Reinvestigation of fractions derived from large-scale fractionation of Maytenus
      buchananii led to the isolation of two new maytansinoids. The structures of these
      principles were determined using electrospray MS, 1H NMR, 13C NMR, and 2D NMR
      techniques. One principle was found to be 2'-N-demethylmaytanbutine (2), while
      the other was found to be maytanbicyclinol (3), the first maytansinoid with two
      macrocyclic rings to be isolated from a Maytenus species.

PMID- 10075789
TI  - Oumarone, bissaone, and aissatone, unusual prenylated polyketides from harrisonia
      abyssinica 
AB  - Fractionation of the n-hexane extract of the leaves of Harrisonia abyssinica,
      collected in Guinea, afforded three novel and unusual prenylated polyketides,
      which were named oumarone (1), bissaone (2), and aissatone (3). Their structures
      were elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy.

PMID- 10075790
TI  - Arieianal, a prenylated benzoic acid from piper arieianum 
AB  - A new prenylated benzoic acid, arieianal [3,4-dihydroxy-5-(E,E, E-11'-formyl
      3',7',15'-trimethylhexadeca-2',6',10', 14'-tetraenyl)benzoic acid, 1], has been
      isolated from the leaves of Piper arieianum and assigned this structure on the
      basis of its spectral data.

PMID- 10075791
TI  - Biological activities of 7-epiclusianone.
AB  - 7-Epiclusianone, isolated from Rheedia gardneriana, was tested in several
      biological assays. It was active in vitro against trypomastigotes of Trypanosoma
      cruzi but inactive in vivo in experimentally infected mice. It was also active
      against Artemia salina, but inactive against the fungus Cladosporium
      sphaerospermum and the snail Biomphalaria glabrata.

PMID- 10075792
TI  - Palythoalones A and B, new ecdysteroids from the marine zoanthid
      palythoaaustraliae 
AB  - Two new ecdysteroids, palythoalones A (1) and B (2), have been isolated from the
      marine zoanthid Palythoa australiae. The structures have been elucidated on the
      basis of spectroscopic data and by chemical means.

PMID- 10075793
TI  - Three new scalarane-based sesterterpenes from the tropical marine sponge
      strepsichordaia lendenfeldi1 
AB  - From the dichloromethane extract of the tropical marine sponge Strepsichordaia
      lendenfeldi collected from the Great Barrier Reef, Australia, three new (1, 2,
      and 9) and seven known (3-8 and 10) scalarane-based sesterterpenes were isolated.
      All molecular structures were secured by spectroscopic methods, particularly 1D
      and 2D NMR, and accurate mass measurement.

PMID- 10075794
TI  - N-methylquinolinium 2-carboxylate, a defensive betaine from Photuris versicolor
      fireflies.
AB  - From whole body extracts of Photuris versicolor fireflies, the defensive betaine
      N-methylquinolinium 2-carboxylate (1) was isolated and characterized on the basis
      of spectroscopic data and comparison with a synthetic sample.

PMID- 10075795
TI  - Acylated flavonoids from pseudognaphalium species 
AB  - Two new acylated flavonoids have been isolated from the resinous exudates of
      Pseudognaphalium robustum and Pseudognaphalium cheirantifolium. Their structures
      were elucidated by high-resolution spectroscopic methods as 5,7,8-trihydroxy-3
      methoxyflavone 8-O-[(E)-2-methyl-2-butenoate] (1) and 5,7,8-trihydroxy-3, 6
      dimethoxyflavone 8-O-[(E)-2-methyl-2-butenoate] (2).

PMID- 10075796
TI  - Halogenated monoterpenes from plocamium costatum and their biological activity1 
AB  - From the dichloromethane solubles of the temperate red alga Plocamium costatum,
      one new [1,4-dibromo-2,3,6-trichloro-3, 7-dimethyl-7-octene] (1) and three
      previously reported polyhalogenated monoterpenes (2-4), and the known phytol
      derivative 3,7,11,15-tetramethylhexadec-1-en-3-ol (1-phyten-3-ol, 5) were
      isolated. The structure of 1 was deduced from its spectroscopic data. For
      compound 3, complete 1H and 13C NMR data are reported for the first time. The
      CH2Cl2 extract and compounds 3 and 5 deterred settlement of barnacle larvae,
      suggesting a potential ecological role of these isolates.

PMID- 10075797
TI  - Antifungal and antibacterial metabolites from a sclerotium-colonizing isolate of
      Mortierella vinacea.
AB  - The known compound methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (1) and three new
      related metabolites, which we have named mortivinacins A (2), B (3), and C (4),
      were identified as metabolites of the fungus Mortierella vinacea. Nicotinic acid
      (5) was also encountered. This isolate of M. vinacea was obtained from an
      Aspergillus flavus sclerotium during field studies of sclerotium longevity in
      soil. Compounds 1-5 were isolated by chromatographic fractionation of organic
      extracts from M. vinacea solid-substrate fermentation cultures, and the
      structures were assigned by analysis of NMR and MS data. Compounds 1, 2, and 5
      were responsible for the antibacterial and antifungal activities of the extract.

PMID- 10075798
TI  - A cyclized didemnimide alkaloid from the caribbean ascidian didemnumconchyliatum 
AB  - A novel, cyclized alkaloid of the didemnimide class, 5, has been isolated from
      extracts of the Caribbean ascidian Didemnum conchyliatum. The structure of 5 was
      assigned using combined spectral methods that emphasized one- and two-dimensional
      NMR methods. The new alkaloid is the cyclization product of didemnimide A (1)
      formed via a C-2 indole condensation with the imidazole nitrogen.

PMID- 10075799
TI  - A novel 2-hydroxyflavanone from collinsonia canadensis 
AB  - A new flavonoid, 2,5-dihydroxy-6,7-dimethoxyflavanone (1), was isolated from the
      leaf and stem exudates of Collinsonia canadensis along with three known flavones,
      baicalein-6,7-dimethyl ether (2), norwogenin-7,8-dimethyl ether (3), and
      tectochrysin (5-hydroxy-7-methoxyflavone).

PMID- 10075800
TI  - A new sesquiterpene as an antifouling substance from a palauan marine sponge,
      dysidea herbacea 
AB  - Bioassay-guided fractionation of an extract from a marine sponge, Dysidea
      herbacea, led to the isolation and identification of the new sesquiterpene 1.
      This compound showed repellent activity against the blue mussel, Mytilus edulis
      galloprovincialis.

PMID- 10075801
TI  - 8-methyl-pyridoxatin: A novel N-hydroxy pyridone from fungus OS-F61800 that
      induces erythropoietin in human cells.
AB  - In the course of screening for small-molecule modulators of erythropoietin gene
      expression, a novel N-hydroxy pyridone was isolated from a culture of OS-F61800.
      Its structure was elucidated by extensive 1H and 13C NMR spectroscopic and
      chemical studies. This compound induced erythropoietin gene expression fivefold
      at a concentration of 0.3 microM, which is about threefold greater potency than
      our previously identified erythropoietin inducers.

PMID- 10075803
TI  - A new biologically active acylated triterpene saponin from silene fortunei 

PMID- 10075802
TI  - Efficient conversion of aucubin into 6-epi-aucubin 
AB  - Selective deprotection of peracetylaucubin (3) by use of KCN led to 6-O
      acetylaucubin (4), which was readily converted into 2',3',4',6', 10-penta-O
      benzoylaucubin (7). Configuration inversion performed on 7, using a modified
      Mitsunobu reaction, followed by deprotection, afforded 6-epi-aucubin (2).

PMID- 10075804
TI  - Internet biomolecular resources.

PMID- 10075805
TI  - An immunological assay for determination of baculovirus titers in 48 hours.
AB  - Th baculovirus expression system is a system of choice for expressing eukaryotic
      proteins. Large amounts of biologically active material can be generated using
      this system by infecting insect cells with a baculovirus expressing the target
      protein. At several stages during the production of a baculovirus stock, it is
      necessary to titer the virus. Current methods have long time lines and are either
      technically difficult or are limited to viruses expressing a reporter gene. The
      new assay described here yields titers in 48 h, is easy to perform using 96-well
      plates, and is applicable to any Autographa californica nucleopolyhedrovirus
      based recombinant baculovirus. This assay uses an antibody to a viral envelope
      glycoprotein to detect infected cells via immunostaining. The titer is determined
      by counting foci of infection under a light microscope. The required incubation
      period is shortened considerably because infected cells express viral antigens
      long before the macroscopic signs of infection scored in other assays become
      apparent. Titers determined using this immunological assay are comparable, both
      in value and variability, to those obtained using a traditional method, provided
      that the stocks have titers above 10(4) pfu/ml.

PMID- 10075806
TI  - A two-step selection approach for the identification of ligand-binding
      determinants in cytokine receptors.
AB  - We have developed a novel cell-based method for the isolation and selection of
      mutant cytokine receptors with defects in ligand binding and applied it to the
      human interleukin-4 receptor. The experimental procedure is based upon the
      functional heterologous expression of receptor mutants in eukaryotic cells
      followed by a two-step selection procedure. Positive selection for cells that
      express receptor variants is achieved by means of an agonistic antibody that
      mediates cell survival through receptor dimerization. An IL-4-coupled toxin is
      subsequently used to select against cells expressing wild-type receptors. Cells
      expressing mutant receptors that are unable to bind the cytotoxic ligand survive
      and can be amplified. The procedure allows the isolation of rare receptor
      variants from cell pools containing predominantly wild-type cells. This method,
      which should be equally applicable to similar receptor systems, was used to
      demonstrate the importance of a critical charged amino acid residue in the human
      IL-4 receptor alpha-subunit for IL-4-induced receptor activation.

PMID- 10075807
TI  - Rayleigh light scattering study on the reaction of nucleic acids and methyl
      violet.
AB  - A new quantitative determination method for nucleic acids in aqueous solutions,
      based on the enhancement of Rayleigh light scattering of methyl violet by nucleic
      acids, has been developed. The sensitivity of the assay allows amounts of nucleic
      acids as little as 100 ng/ml to be quantitated reliably. In addition to its high
      sensitivity, this method has other advantages: rapidity of reaction (<5 min),
      simplicity of operation (one-step assay), commonality of spectrofluorimeter and
      reagents, stability of mixtures formed, and reproducibility. Under the
      experimental conditions, there is little or no interference from proteins,
      nucleosides, and most metal ions. Interference by a few metal ions, detergents,
      and some salts can be minimized by dilution. The method can also be used to
      determine the total amount of nucleic acids without the arduous choice of
      standard and difficult separation of DNA and RNA.

PMID- 10075808
TI  - A two-dimensional support for selective binding of polyhistidine-tagged proteins:
      identification of a proliferating cell nuclear antigen point mutant with altered
      function in vitro.
AB  - Whatman 3MM paper was chemically modified to generate nickel-charged
      iminodiacetic acid paper (Ni2+-IDA paper). Bacteria were transformed with
      Escherichia coli expression plasmids coding for either unmodified proliferating
      cell nuclear antigen (PCNA) or PCNA containing a genetically engineered
      polyhistidine tract (his-tag) located at its NH2 terminus. They were then grown,
      induced, and lysed, and macromolecules were transferred to Ni2+-IDA paper. After
      exhaustive washing, his-tagged PCNA but not unmodified PCNA remained bound to the
      paper. Moreover, bound his-tagged PCNA was biochemically active in an in situ DNA
      synthesis assay with exogenous template-primer and purified calf thymus DNA
      polymerase delta (pol delta). Ni2+-IDA paper was used to identify a PCNA- point
      mutant that, relative to wild-type PCNA, promotes increased DNA synthesis by pol
      delta beyond a model abasic template site. In addition, metal-charged IDA paper
      promises to be generally useful for functional screening of cells expressing
      cloned proteins.

PMID- 10075809
TI  - Buffer effects on EcoRV kinetics as measured by fluorescent staining and digital
      imaging of plasmid cleavage.
AB  - We have developed a protocol to quantify polymer DNA cleavage which replaces the
      traditional radiolabeling and scintillation counting with fluorescent staining
      and digital imaging. This procedure offers high sensitivity, speed, and
      convenience, while avoiding waste and error associated with traditional 32P
      radiolabeling. This protocol was used to measure cleavage of pBR322 plasmid DNA
      by EcoRV, a type II restriction enzyme. EcoRV was found to exhibit an order of
      magnitude difference in binding in two apparently similar buffers used in
      previous investigations. To determine the origin of this effect, we measured
      reaction kinetics in buffers of different chemical nature and concentration:
      Tris, bis-Tris propane, Tes, Hepes, and cacodylate. We found that buffer
      concentration and identity had significant effects on EcoRV reaction velocity
      through large changes in specific binding and nonspecific binding (reflected in
      the Michaelis constant Km and the dissociation constant for nonspecific binding
      Kns). There were only small changes in Vmax. The source of the buffer effect is
      the protonated amines common to many pH buffers. These buffer cations likely act
      as counterions screening DNA phosphates, where both the protonated buffer
      structure and concentration affect enzyme binding strength. It appears that by
      choosing anionic buffers or zwitterionic buffers with a buried positive charge,
      buffer influence on the protein binding to DNA can be largely eliminated.

PMID- 10075810
TI  - A novel high-performance anion-exchange chromatographic method for the analysis
      of carrageenans and agars containing 3,6-anhydrogalactose.
AB  - A novel method has been developed to determine the sugar composition of 3,6
      anhydrogalactose-containing polysaccharides, such as carrageenan and agar. The
      method is based on reductive hydrolysis with a methylmorpholine-borane complex in
      the presence of acid and subsequent high-performance anion-exchange
      chromatography analysis of the alditols without any derivatization. The method
      was validated by 13C NMR analysis of six carrageenans and three agars and by a
      previously used method based on derivatization to alditol acetates and gas-liquid
      chromatography analysis. The new method was found to be superior to the gas
      liquid chromatography method as the analysis time was less than half. Also it was
      found to be more accurate and reproducible and no derivatization was required.
      The analysis of the six different carrageenan samples revealed that homogeneous
      mu- and nu-carrageenan, theoretically without 3,6-anhydrogalactose residues,
      cannot be isolated from red seaweeds. Consequently, the question arose if mu- and
      nu-carrageenans at all are present in seaweeds and if the current hypotheses
      regarding biosynthesis of carrageenans in the seaweeds are correct. The data
      demonstrated that carrageenans are highly complex natural polysaccharides, which
      are more irregular than assumed hitherto. The new analytical technique will
      permit elucidation of the detailed structure of seaweed polysaccharides and
      determination of their structure-property relationships.

PMID- 10075811
TI  - Mediated, amperometric biosensor for glucose-6-phosphate monitoring based on
      entrapped glucose-6-phosphate dehydrogenase, Mg2+ ions, tetracyanoquinodimethane,
      and nicotinamide adenine dinucleotide phosphate in carbon paste.
AB  - In this study, an amperometric carbon paste biosensor is developed for glucose-6
      phosphate (G6P) monitoring which is based on entrapped Mg2+ ions, G6P
      dehydrogenase, NADP+ polyethylenimine (PEI) and the electroactive mediator,
      tetracyanoquinodimethane (TCNQ). The calibration line had a slope of 1.55 x 10(
      5) A. M-1 with a correlation coefficient of 0.9965. The limit of detection
      (defined as three times the standard deviation of the response of the electrode
      to blank phosphate buffer injections (noise)) of the G6P biosensor was 5.0 x 10(
      5) M. The application of this biosensor for monitoring G6P in human blood using
      the standard addition method is also demonstrated. A two-parameter empirical
      equation which adequately describes the deactivation of the biosensor steady
      state response with time is also proposed.

PMID- 10075812
TI  - Mass spectrometric analysis of catechol-histidine adducts from insect cuticle.
AB  - Adducts of catechols and histidine, which are produced by reactions of 1,2
      quinones and p-quinone methides with histidyl residues in proteins incorporated
      into the insect exoskeleton, were characterized using electrospray ionization
      mass spectrometry (ESMS), tandem electrospray mass spectrometry (ESMS-MS,
      collision-induced dissociation), and ion trap mass spectrometry (ITMS). Compounds
      examined included adducts obtained from acid hydrolysates of Manduca sexta
      (tobacco hornworm) pupal cuticle exuviae and products obtained from model
      reactions under defined conditions. The ESMS and ITMS spectra of 6-(N-3')
      histidyldopamine [6-(N-3')-His-DA, pi isomer] isolated from M. sexta cuticle were
      dominated by a [M + H]+ ion at m/z 308, rather than the expected m/z 307. High
      resolution fast atom bombardment MS yielded an empirical formula of C14H18N3O5,
      which was consistent with this compound being 6-(N-1')-histidyl-2-(3, 4
      dihydroxyphenyl)ethanol [6-(N-1')-His-DOPET] instead of a DA adduct. Similar
      results were obtained when histidyl-catechol compounds linked at C-7 of the
      catechol were examined; the (N-1') isomer was confirmed as a DA adduct, and the
      (N-3') isomer identified as an (N-1')-DOPET derivative. Direct MS analysis of
      unfractionated cuticle hydrolysate revealed intense parent and product ions
      characteristic of 6- and 7-linked adducts of histidine and DOPET. Mass
      spectrometric analysis of model adducts synthesized by electrochemical oxidative
      coupling of N-acetyldopamine (NADA) quinone and N-acetylhistidine (NAcH)
      identified the point of attachment in the two isomers. A prominent product ion
      corresponding to loss of CO2 from [M + H]+ of 2-NAcH-NADA confirmed this as being
      the (N-3') isomer. Loss of (H2O + CO) from 6-NAcH-NADA suggested that this adduct
      was the (N-1') isomer. The results support the hypothesis that insect cuticle
      sclerotization involves the formation of C-N cross-links between histidine
      residues in cuticular proteins, and both ring and side-chain carbons of three
      catechols: NADA, N-beta-alanyldopamine, and DOPET.

PMID- 10075813
TI  - Effects of phosphatidylcholine/phosphatidylethanolamine composition in
      cholesteryl ester-micellar substrates on neutral cholesterol esterase activity.
AB  - The effect of phospholipid composition in cholesteryl ester (CE)-micellar
      substrates on neutral cholesterol esterase (N-CEase) activity was examined. N
      CEase preparation was incubated with micelles composed of cholesteryl-[1-14C]
      oleate, sodium taurocholate, and phosphatidylcholine
      (PC)/phosphatidylethanolamine (PE) at varying ratios (%PE:0 = PC only, 17, 33,
      50, 66, 83). The activity increased dependently with the increase in PE content;
      the activity with the micelles containing the highest ratio of PE was 2.5-fold
      compared with the micelles consisting of PC only. Vmax with the micelles of 83,
      66, and 50% PE was 3.1-, 2.7-, and 1.9-fold, respectively, compared with the
      micelles of PC only. Each micellar preparation was chromatographed through a
      Superose 6 column by the FPLC system. In 66 and 83% PE-containing micelles, PC,
      PE, CE, and part of sodium taurocholate eluted completely together in a single
      peak, whereas in micelles with 33 and 50% PE they eluted loosely together. The
      micelles with PC only or 17% PE formed PC-micelles without including CE and PE.
      It is concluded that PE plays a critical role in the formation of CE micelles
      with PC, and in the interaction with N-CEase. The CE-micelles with 66-83% PE
      serve as substrates for sensitive and reproducible N-CEase assay.

PMID- 10075814
TI  - A continuous fluorometric assay for leukotriene D4 hydrolase.
AB  - A fluorogenic substrate for assay of leukotriene D4 hydrolase (LTDase; EC
      3.4.13.19) has been prepared and evaluated, using enzyme purified from porcine
      kidney. The compound is based on internal quenching of the synthetic, fluorescent
      amino acid d, l-2-amino-3-(7-methoxy-4-coumaryl)propanoic acid (d,l-Amp) by a 2,
      4-dinitrophenyl (DNP) group. The compound is epsilon-DNP-l-Lys-d-Amp which
      incorporates the D-isomer of Amp to exploit the unique ability among mammalian
      peptidases for LTDase to hydrolyze peptides containing a d-amino acid in the C
      terminal position. epsilon-DNP-l-Lys-d-Amp was found to be an excellent substrate
      for LTDase, with Km value of 370 microoffUnder the conditions of assay, the
      substrate was without noticeable quenching effect on the fluorescence of the
      product (d-Amp) liberated by the action of LTDase. Using porcine kidney
      microvillar membranes, which contain a battery of peptidases, the specific
      inhibitor of LTDase, cilastatin, completely inhibited the breakdown of epsilon
      DNP-l-Lys-d-Amp, indicating that the substrate is selective for LTDase.

PMID- 10075815
TI  - Electrospray ionization mass spectrometric analysis of blood for differentiation
      of species.
AB  - The National Fish and Wildlife Forensic Laboratory is responsible for the
      determination of species of birds, reptiles, and mammals from the United States,
      as well as international species falling under the protection of CITES treaties.
      We have recently found electrospray ionization mass spectrometry to be an
      effective means of rapidly analyzing blood samples for species identification.
      Nearly 1000 individuals were analyzed which comprised 62 species represented by
      birds, mammals, and reptiles. Whole blood and dried blood samples were analyzed
      without purification to provide simultaneous molecular weights from the alpha-
      and beta-proteins present in each sample's hemoglobin. The combination of the two
      molecular weights for the hemoglobin proteins (i.e., alpha/beta-pairs) was used
      as species determining markers. In all, 133 distinctive alpha/beta-pairs were
      observed from the individuals analyzed. Despite the variability in the
      hemoglobins evaluated, 86% of these alpha/beta-pairs were found to be diagnostic
      for a particular species to the exclusion of all other species studied. No other
      single protein system studied by a single analytical technique can so effectively
      resolve species from a wide range of taxa as can the hemoglobin system when
      analyzed by electrospray ionization mass spectrometry.

PMID- 10075816
TI  - Expression and analysis of green fluorescent proteins in human embryonic kidney
      cells by capillary electrophoresis.
AB  - The green fluorescent protein (GFP) has attracted much interest as a reporter for
      gene expression. In this paper, application of capillary electrophoresis with
      laser-induced fluorescent (CE-LIF) for quantitation of green fluorescence protein
      in cellular extracts and single cells is investigated. The S65T mutant form of
      GFP protein was successfully expressed in human embryonic kidney (HEK293) cells,
      and its production was confirmed by fluorescence microscopy and CE-LIF. The mass
      limit of detection for the mutant S65T was 5.3 x 10(-20) mol, which was better
      than that for the wild-type GFP by a factor of six. Detection of a small amount
      of GFP is difficult by conventional techniques such as fluorescent microscopy due
      to interference from cell autofluorescence at low GFP concentrations. The HEK293
      cells were transfected with the GFP plasmid that produced S65T-GFP. Transient
      production of S65T protein was detected 2 h after the transfection and reached a
      maximum after 48 h. The protein concentration began to decrease significantly
      after 96 h. Single cell analysis of HEK293 cells after transfection with GFP
      plasmid indicate a nonuniform production of S65T-GFP protein among cells.

PMID- 10075817
TI  - A continuous fluorescence assay for the study of P-glycoprotein-mediated drug
      efflux using inside-out membrane vesicles.
AB  - A fluorimetric procedure for assaying the transport activity of P-glycoprotein (P
      gp) using a membrane vesicle model has been developed. In this assay methylene
      blue is incorporated into inside-out vesicles prepared from human acute
      lymphoblastic leukemic cells resistant to 100 ng. ml-1 vinblastine (VBL100) and
      their sensitive controls. The fluorescence of a fluorescent derivative of
      colchicine (fluorescein-colchicine) is quenched as the probe is transported
      across the vesicle membrane. The fluorescein-colchicine transport was found to be
      dependent on the presence of P-glycoprotein, required ATP, and was inhibited by
      vanadate and the reversal agent, verapamil, in a dose-dependent manner.
      Furthermore, the transport was competed against by the P-gp substrates,
      vinblastine and methotrexate. The transport of fluorescein-colchicine by P-gp was
      found to be cooperative (n = 1. 23). The assay is rapid, requires small amounts
      of sample, and removes the need for the radioactive procedures used in the past.
      The assay should find use in characterizing the transport kinetics of P-gp, for
      examining and optimizing combinations of chemotherapeutics, and for examining the
      effects of reversal agents and substrates which potentially compete for transport
      with the fluorescent substrate probe. Other possible applications include
      examining P-gp-mediated transport properties of purified P-gp in reconstituted
      systems.

PMID- 10075818
TI  - Characterization of SYBR Gold nucleic acid gel stain: a dye optimized for use
      with 300-nm ultraviolet transilluminators.
AB  - The highest sensitivity nucleic acid gel stains developed to date are optimally
      excited using short-wavelength ultraviolet or visible light. This is a
      disadvantage for laboratories equipped only with 306- or 312-nm UV
      transilluminators. We have developed a new unsymmetrical cyanine dye that
      overcomes this problem. This new dye, SYBR Gold nucleic acid gel stain, has two
      fluorescence excitation maxima when bound to DNA, one centered at approximately
      300 nm and one at approximately 495 nm. We found that when used with 300-nm
      transillumination and Polaroid black-and-white photography, SYBR Gold stain is
      more sensitive than ethidium bromide, SYBR Green I stain, and SYBR Green II stain
      for detecting double-stranded DNA, single-stranded DNA, and RNA. SYBR Gold
      stain's superior sensitivity is due to the high fluorescence quantum yield of the
      dye-nucleic acid complexes ( approximately 0.7), the dye's large fluorescence
      enhancement upon binding to nucleic acids ( approximately 1000-fold), and its
      capacity to more fully penetrate gels than do the SYBR Green gel stains. We found
      that SYBR Gold stain is as sensitive as silver staining for detecting DNA-with a
      single-step staining procedure. Finally, we found that staining nucleic acids
      with SYBR Gold stain does not interfere with subsequent molecular biology
      protocols.

PMID- 10075819
TI  - Quantitative analysis of alachlor protein adducts by gas chromatography-mass
      spectrometry.
AB  - This study examined the potential use of hemoglobin (Hb)- and serum-protein
      adducts of alachlor as potential biomarkers of alachlor exposure, a genotoxic and
      carcinogenic herbicide. The method developed was based on the observation that
      cleavage of S-cysteinyl alachlor-protein adducts by methanesulfonic acid gave the
      rearrangement product 3-(2',6'-diethylphenyl)-1, 3-thiazolidine-4-one (TZO). The
      structure of TZO was confirmed by mass spectroscopy, NMR spectroscopy, and
      independent synthesis. In the assay, treatment of alachlor-cysteinyl protein
      adducts by methanesulfonic acid was followed by extraction and analysis. TZO was
      detected and quantitated by electron-impact GC/MS in the single ion-monitoring
      mode. [ring-13C6]Alachlor-N-acetylcysteine was added as an internal standard
      prior to treatment and was converted to [ring-13C6]TZO, allowing response factors
      to be used to quantitate TZO concentrations. Incubations of alachlor (0-1000
      microM) with human albumin and bovine serum albumin (BSA) resulted in linear
      adduct formation with both proteins. Maximal adduction levels of 613-1130 pmol
      alachlor-albumin adducts/mg protein were observed, with BSA binding close to
      twice that of human albumin. A linear concentration response of alachlor-Hb
      adducts was observed when whole blood from female CD rats was incubated with
      alachlor in vitro at concentrations up to 300 microM. Maximal binding was 1860
      pmol alachlor-Hb adducts/mg globin. Male CD rats treated with alachlor at 150
      mg/kg body wt/day ip for 0, 1, 2, and 3 days were sacrificed 4 days after final
      dosing. A maximal binding of 2250 pmol alachlor-Hb adducts/mg globin was
      observed. This assay provides a new approach for biomonitoring alachlor levels in
      experimental animals and has the potential for use in humans.

PMID- 10075821
TI  - Protein sequencing by matrix-assisted laser desorption ionization-postsource
      decay-mass spectrometry analysis of the N-Tris(2,4,6-trimethoxyphenyl)phosphine
      acetylated tryptic digests.
AB  - We have recently reported a simple procedure by which low picomole quantities of
      peptides can be modified to the corresponding N-Tris(2, 4,6
      trimethoxyphenyl)phosphonium-acetyl (TMPP-Ac) derivatives (Z. H Huang, J. Wu, D.
      A. Gage, and J. T. Watson, Anal. Chem. 69, 137-144, 1997). This modification
      significantly facilitates sequence interpretation by providing exclusively N
      terminal product ions (mainly a-type ions) in the fast-atom bombardment-MS/MS and
      matrix-assisted laser desorption ionization-postsource decay(MALDI-PSD)-MS
      spectra. The TMPP-Ac derivatization approach has been extended now for the direct
      derivatization of tryptic digests originating from 1-5 microg of proteins with
      molecular weights from 10-120 kDa. Our new procedure involves tryptic digestion
      in aqueous solution buffered to pH 8-8.2 with phosphate or Tris-HCl, followed by
      reaction with TMPP-acetic acid N-hydroxysuccinimide ester (TMPP-AcOSu bromide, 2
      4 nmol reagent/microg protein, rt, 20 min) to provide N-terminally derivatized
      products, while the epsilon-NH2 groups in lysine remain unchanged. The resultant
      derivatized peptide mixture or its partially separated HPLC fractions are
      subsequently analyzed by MALDI-PSD-MS using 0.5- to 1-pmol aliquots, giving rise
      to product ion spectra that are easily interpretable. As there is no need for
      material transfer and change of buffer media, the tandem enzymatic-chemical
      reaction/MS analysis process is usually carried out with very high throughput
      (digestion, 1 h; reaction, 1/3 h; HPLC, 1 h; MALDI-PSD, 3-4 fragments/h). This
      procedure will be of potential use for obtaining sequence information directly
      from mixtures or as an adjunct of peptide mass mapping to provide protein
      identification with high confidence.

PMID- 10075820
TI  - A fluorescence resonance energy transfer approach for monitoring protein-mediated
      glycolipid transfer between vesicle membranes.
AB  - A lipid transfer protein, purified from bovine brain (23.7 kDa, 208 amino acids)
      and specific for glycolipids, has been used to develop a fluorescence resonance
      energy transfer assay (anthrylvinyl-labeled lipids; energy donors and perylenoyl
      labeled lipids; energy acceptors) for monitoring the transfer of lipids between
      membranes. Small unilamellar vesicles composed of 1 mol% anthrylvinyl
      galactosylceramide, 1.5 mol% perylenoyl-triglyceride, and 97.5% 1-palmitoyl-2
      oleoyl phosphatidylcholine (POPC) served as donor membranes. Acceptor membranes
      were 100% POPC vesicles. Addition of glycolipid transfer protein to mixtures of
      donor and acceptor vesicles resulted in increasing emission intensity of
      anthrylvinyl-galactosylceramide and decreasing emission intensity of the
      nontransferable perylenoyl-triglyceride as a function of time. The behavior was
      consistent with anthrylvinyl-galactosylceramide being transferred from donor to
      acceptor vesicles. The anthrylvinyl and perylenoyl energy transfer pair offers
      advantages over frequently used energy transfer pairs such as NBD and rhodamine.
      The anthrylvinyl emission overlaps effectively the perylenoyl excitation spectrum
      and the fluorescence parameters of the anthrylvinyl fluorophore are nearly
      independent of the medium polarity. The nonpolar fluorophores are localized in
      the hydrophobic region of the bilayer thus producing minimal disturbance of the
      bilayer polar region. Our results indicate that this method is suitable for assay
      of lipid transfer proteins including mechanistic studies of transfer protein
      function.

PMID- 10075822
TI  - A scintillation proximity assay for the Raf/MEK/ERK kinase cascade: high
      throughput screening and identification of selective enzyme inhibitors.
AB  - We have developed a quantitative scintillation proximity assay (SPA) that
      reproduces the Raf/MEK/ERK signal transduction pathway. The components of this
      assay include human cRaf1, MEK1, and ERK2 and a biotinylated peptide substrate
      for ERK2. cRaf1 was expressed as a his-tagged protein in insect cells in an
      active form. MEK1 and ERK2 were expressed in Escherichia coli as glutathione S
      transferase (GST)-fusion proteins in their inactive forms. ERK2 was removed from
      the GST portion of the fusion protein by cleavage with thrombin protease. When
      the purified components are incubated together, cRaf-1 phosphorylates and
      activates MEK1, MEK1 phosphorylates and activates ERK2, and ERK2 phosphorylates
      the peptide, biotin-AAATGPLSPGPFA. Phosphorylation of the peptide using [gamma
      33P]ATP is detected following binding to streptavidin-coated SPA beads. The assay
      detects inhibitors of cRaf1, MEK1, or ERK2, and has been used to screen large
      numbers of compounds. The specific target of inhibition was subsequently
      identified with secondary assays described herein.

PMID- 10075823
TI  - Is nitrocellulose filter binding really a universal assay for protein-DNA
      interactions?
AB  - The ability to bind to nitrocellulose is commonly accepted as being a universal
      property of proteins and has been widely used in many different fields of study.
      This property was first exploited in the study of DNA-binding proteins 30 years
      ago, in studies involving DNA binding by the lactose repressor (LacR) of
      Escherichia coli. Termed the filter-binding assay, it remains the quickest and
      easiest assay available for the study of protein-DNA interactions. However, the
      exact mechanism by which proteins bind to nitrocellulose remains uncertain. Given
      the supposedly universal nature of the interaction, we were surprised to notice
      that certain LacR variants were completely unable to bind simultaneously to DNA
      containing a single lac operator and nitrocellulose. Investigation of this loss
      of binding suggests that LacR requires a protein region that is both hydrophobic
      in nature and more or less unstructured, in order to bind to both nitrocellulose
      and DNA. In the case of wild-type, tetrameric LacR, the DNA-recognition domain
      that is not bound to DNA suffices. Dimeric LacR variants will only bind if they
      have certain C-terminal extensions. These experiments sound a cautionary note for
      the use of filter binding as an assay of choice, particularly in applications
      involving screening for the DNA-binding site of putative DNA-binding proteins.

PMID- 10075824
TI  - The determination of phospholipase D activity in emulsion systems.
AB  - Although phospholipase D (PLD) is often used in emulsion systems consisting of
      buffer and a nonpolar organic solvent, most activity assays have been designed to
      work in purely aqueous milieu. Here a method is described for the determination
      of PLD activity in emulsion systems. The assay is based on the
      transphosphatidylation of phosphatidylcholine with 1-butanol in
      dichloromethane/buffer with the subsequent densitometric quantification of the
      products after their separation by HPTLC and staining with a CuSO4/H3PO4 reagent.
      The method is particularly appropriate for the determination of enzymes such as
      PLD from Streptomyces sp. that prefer the exchange of the head group in
      glycerophospholipids to their hydrolysis. Since the application of an organic
      solvent in the PLD assay allows the determination of the enzyme in analytes
      insoluble in aqueous media, the method can also be used to determine PLD activity
      in the presence of high concentrations of phospholipids.

PMID- 10075825
TI  - Interactions of myristoylated alanine-rich C kinase substrate (MARCKS)-related
      protein with a novel solid-supported lipid membrane system (TRANSIL).
AB  - The determination of partition coefficients is crucial for the biochemical
      analysis of membrane-based processes, but requires tedious procedures. We have
      facilitated this analysis using a silica gel coated with a single phospholipid
      bilayer (TRANSIL) as the membranous phase. We demonstrate the validity of this
      method using MARCKS-related protein, a 20-kDa member of the MARCKS family (an
      acronym for myristoylated alanine-rich C kinase substrate). The partition
      coefficients describing the association of unmyristoylated and myristoylated
      MARCKS-related protein with membranes of different phospholipid composition are
      in agreement with previous work with vesicles and show that both the myristoyl
      moiety and the basic effector domain of MARCKS-related protein mediate the
      binding. However, no significant cooperativity is observed between these two
      domains. Interestingly, MARCKS-related protein binds to TRANSIL membranes more
      strongly at temperatures below their phase-transition temperature. Taking
      advantage of this property, MARCKS-related protein was purified by phase
      transition chromatography, loading Escherichia coli lysates on a TRANSIL column
      at 4 degrees C and eluting MRP at room temperature. In conclusion, TRANSIL is a
      versatile tool to determine the affinity of compounds for phospholipid membranes
      and to purify membrane-bound proteins. TRANSIL should also enable functional
      studies of protein-ligand and protein-protein interactions at the surface of
      membranes.

PMID- 10075826
TI  - Covalent immobilization of unilamellar liposomes in gel beads for chromatography.
AB  - For immobilized (proteo)liposome chromatography, unilamellar liposomes were
      covalently bound within gel beads that had been activated by CNBr, N
      hydroxysuccinimide, tresyl, or chloroformate. Liposomes composed of
      phosphatidylcholine (PC) and 2 mol% of amino-containing lipid
      (phosphatidylethanolamine-caproylamine) were immobilized in the activated gels at
      5-35 micromol lipid/ml gel and yields of 11-70%. The highest immobilized amount
      was found in chloroformate-activated TSK G6000PW gel, which contains large pore
      size (>100 nm). Liposomes composed of PC alone could also be attached to the
      chloroformate-activated gels at 33-42 micromol/ml gel and yields of 58-65%,
      probably by crosslinking of the phosphate moiety of phospholipid with the active
      group of the adsorbent. Liposomes prepared by various phospholipids with or
      without amino-containing lipids can generally be immobilized in the chloroformate
      activated gels. The covalently bound liposomes were characterized by their high
      stability, unilamellarity, permeability of the membranes, and drug-membrane
      partition properties. A stable membrane phase was constructed for chromatographic
      experiments to be performed under extreme elution conditions.

PMID- 10075827
TI  - Use of bacteriophage T7 displayed peptides for determination of monoclonal
      antibody specificity and biosensor analysis of the binding reaction.
AB  - A heptapeptide library displayed by bacteriophage T7 was used to characterize
      epitopes of the monoclonal antibodies F4, F5, and LT1 directed against mouse
      polyomavirus large T-antigen. Phage selected by biopanning was cloned by plaque
      isolation, and the binding specificity of individual clones was confirmed by
      enzyme-linked immunosorbent assay. In phage reacting with the F5 antibody the
      deduced amino acid sequence of the displayed peptides corresponded to a segment
      of large T-antigen. In phage reacting with the antibodies F4 and LT1, no such
      similarity was observed. The kinetics of phage particle-monoclonal antibody
      complex formation and dissociation was analyzed in an optical biosensor
      instrument. Sensor chips of standard quality were useful for binding analysis of
      T7 phage in crude lysates of infected Escherichia coli. We synthesized peptides
      corresponding to selected consensus sequences and showed by biosensor analysis
      that these peptides (linear NH3-CPNSLTPADPTMDY-COOH and NH3-NSLTPCNNKPSNRC-COOH
      with an intramolecular S--S bridge) were able to compete with large T-antigen in
      binding to the corresponding antibodies (LT1 and F4). These synthetic peptides
      were also used for gentle and specific dissociation of large T-antigen-antibody
      complexes. The results demonstrate the potential of phage T7 for display of
      peptides and for rapid analysis of interactions of these peptides with ligands.

PMID- 10075828
TI  - High-throughput nonradioisotopic detection of picomole levels of phosphothreonine
      and phosphoserine containing peptides via biotinylation and enzyme-linked
      immunosorbent assay.
AB  - Determination of phosphorylation sites in proteins is usually accomplished using
      [gamma-32P]ATP. For low-abundance phosphoproteins, in vivo and intact cell
      studies usually require millicurie levels of 32P for a single experiment, making
      multiple experiments prohibitive. Here we describe a low picomole sensitivity,
      nonradioisotopic, high-throughput method for tracing phosphorylation sites in
      proteins and peptides. The method is based on in situ enzyme-linked immunosorbent
      assay (ELISA) plate biotinylation of nonphospho- and phosphopeptides,
      streptavidin capture, and ELISA detection using recently available anti-phospho
      Thr and anti-phospho-Ser antibodies.

PMID- 10075829
TI  - Flow injection microscopy for the study of intracellular calcium mobilization by
      muscarinic agonists.
AB  - The study of cellular response to chemical agonists is essential in understanding
      the complex functions mediated by cell surface receptors. Flow injection
      microscopy has been used with the CHO-M1-WT3 cell line and the fluorescent Ca2+
      indicator Fura-2-AM to monitor mobilization of internal Ca2+. Repeated
      stimulation of cells mounted in an inverted radial flow chamber allows the direct
      comparison of relative intracellular Ca2+ mobilization with respect to agonist
      dose. The process of determining dose-response relationships is simplified since
      an entire dose-response curve can be constructed from a distinct set of cells.
      Use of flow injection lends precision to the application and removal of agonists
      while allowing cellular activity to be monitored throughout the stimulation and
      recovery processes. In this work, dose-response curves have been constructed for
      the muscarinic agonists carbachol, acetylcholine, and pilocarpine resulting in
      EC50 values of 1.7 microM, 56 nM, and 6.8 microM, respectively.

PMID- 10075830
TI  - Reusability of avidin-biotinylated immunoglobulin Y columns in immunoaffinity
      chromatography.
AB  - Reusability of avidin-biotinylated IgY columns for immunoaffinity chromatography
      was examined by repeated use and regeneration. An enzyme-linked immunosorbent
      assay-elution assay using CovaLink NH microtiter plates was used to find the
      optimal conditions for regeneration of columns. Actigel avidin-biotinylated IgY
      column retained about 90% of its initial IgG binding capacity after 50 cycles,
      with 0.1 M glycine-HCl buffer, pH 2.8, as eluent, requiring no regeneration.
      However, IgG binding capacity of UltraLink avidin-biotinylated IgY column
      gradually decreased to 75 and 65% after 10 and 20 cycles, respectively, with the
      commercial eluent, Actisep. Results from the CovaLink NH system agreed with those
      from UltraLink avidin-biotinylated IgY columns. The UltraLink avidin-biotinylated
      IgY column was regenerated twice, by applying 8 M guanidine-HCl, pH 1.6, to
      dissociate biotinylated IgY antibodies from the column. About 40 and 25% of IgG
      binding capacities remained after the first and second regeneration. By applying
      new biotinylated IgY to the treated columns, about 95 and 90% of the initial IgG
      binding capacity before any treatment were recovered. These results demonstrated
      that avidin-biotinylated IgY columns are reusable with or without regeneration
      depending on the avidin-immobilized matrix.

PMID- 10075831
TI  - Detection and quantitation of heteroduplexes can increase the reliability in
      competitive polymerase chain reaction.

PMID- 10075832
TI  - Automated synthesis of peptide nucleic acids and peptide nucleic acid-peptide
      conjugates.

PMID- 10075833
TI  - Preparation of 2-nitro-5-thiobenzoic acid using immobilized Tris(2
      carboxyethyl)phosphine.

PMID- 10075834
TI  - Artificial neural network model for predicting alpha-turn types.

PMID- 10075835
TI  - Preparation of riboflavin 4',5'-cyclic phosphate by incubation of flavin-adenine
      dinucleotide with Mn2+ in the absence of riboflavin 5'-phosphate cyclase.

PMID- 10075836
TI  - Isolation of total RNA from Arabidopsis thaliana seeds.

PMID- 10075837
TI  - Multiple developmental roles for CRAC, a cytosolic regulator of adenylyl cyclase.
AB  - Receptor-mediated activation of adenylyl cyclase (ACA) in Dictyostelium requires
      CRAC protein. Upon translocation to the membrane, this pleckstrin homology (PH)
      domain protein stimulates ACA and thereby mediates developmental aggregation.
      CRAC may also have roles later in development since CRAC-null cells can respond
      to chemotactic signals and participate in developmental aggregation when admixed
      with wild-type cells, but they do not complete development within such chimeras.
      To test whether the role of CRAC in postaggregative development is related to the
      activation of ACA, chemotactic aggregation was bypassed in CRAC-null cells by
      activating the cAMP-dependent protein kinase (PKA). While such strains formed
      mounds, they did not complete fruiting body morphogenesis or form spores.
      Expression of CRAC in the prespore cells of these strains rescued sporulation and
      fruiting body formation. This later function of CRAC does not appear to require
      its PH domain since the C-terminal portion of the protein (CRAC-DeltaPH) can
      substitute for full-length CRAC in promoting spore cell formation and
      morphogenesis. No detectable ACA activation was observed in any of the CRAC-null
      strains rescued by PKA activation and expression of CRAC-DeltaPH. Finally, we
      found that the development of CRAC-null ACA-null double mutants could be rescued
      by the activation of PKA together with the expression of CRAC-DeltaPH. Thus,
      there appears to be a required function for CRAC in postaggregative development
      that is independent of its previously described function in the ACA activation
      pathway.

PMID- 10075838
TI  - Characterisation of a second patched gene in the zebrafish Danio rerio and the
      differential response of patched genes to Hedgehog signalling.
AB  - Hedgehog signalling has been implicated in a variety of processes in vertebrate
      development, and in each case, the activity of Hh proteins is thought to be
      mediated by their interaction with a large multipass transmembrane protein
      encoded by the patched (ptc) gene. In this study we present the full-length
      coding sequence and describe the wild-type expression pattern of a second ptc
      gene in zebrafish, Zf-ptc2. We find that at the sequence level Zf-ptc2 is more
      closely related than Zf-ptc1 to the ptc genes initially characterised in other
      vertebrate species. We also show that transcription of Zf-ptc2, like Zf-ptc1, is
      dependent upon Hh signalling and present evidence that it is activated in
      response to lower levels of Hh activity than is Zf-ptc1. In addition we find no
      evidence for any specificity in the regulatory interactions between the various
      Hh proteins and the two ptc genes in the zebrafish.

PMID- 10075839
TI  - Essential roles of retinoic acid signaling in interdigital apoptosis and control
      of BMP-7 expression in mouse autopods.
AB  - We previously reported that mice lacking the RARgamma gene and one or both
      alleles of the RARbeta gene (i.e., RARbeta+/-/RARgamma-/- and RARbeta-/-/RARgamma
      /- mutants) display a severe and fully penetrant interdigital webbing (soft
      tissue syndactyly), caused by the persistence of the fetal interdigital
      mesenchyme (Ghyselinck et al., 1997, Int. J. Dev. Biol. 41, 425-447). In the
      present study, these compound mutants were used to investigate the cellular and
      molecular mechanisms involved in retinoic acid (RA)-dependent formation of the
      interdigital necrotic zones (INZs). The mutant INZs show a marked decrease in the
      number of apoptotic cells accompanied by an increase of cell proliferation. This
      marked decrease was not paralleled by a reduction of the number of macrophages,
      indicating that the chemotactic cues which normally attract these cells into the
      INZs were not affected. The expression of a number of genes known to be involved
      in the establishment of the INZs, the patterning of the autopod, and/or the
      initiation of apoptosis was also unaffected. These genes included BMP-2, BMP-4,
      Msx-1, Msx-2, 5' members of Hox complexes, Bcl2, Bax, and p53. In contrast, the
      mutant INZs displayed a specific, graded, down-regulation of tissue
      transglutaminase (tTG) promoter activity and of stromelysin-3 expression upon the
      removal of one or both alleles of the RARbeta gene from the RARgamma null genetic
      background. As retinoic acid response elements are present in the promoter
      regions of both tTG and stromelysin-3 genes, we propose that RA might increase
      the amount of cell death in the INZs through a direct modulation of tTG
      expression and that it also contributes to the process of tissue remodeling,
      which accompanies cell death, through an up-regulation of stromelysin-3
      expression in the INZs. Approximately 10% of the RARbeta-/- /RARgamma-/- mutants
      displayed a supernumerary preaxial digit on hindfeet, which is also a feature of
      the BMP-7 null phenotype (Dudley et al., 1995, Genes Dev. 9, 2795-2807; Luo et
      al., 1995, Genes Dev. 9, 2808-2820). BMP-7 was globally down-regulated at an
      early stage in the autopods of these RAR double null mutants, prior to the
      appearance of the digital rays. Therefore, RA may exert some of its effects on
      anteroposterior autopod patterning through controlling BMP-7 expression.

PMID- 10075840
TI  - A hypomorphic myogenin allele reveals distinct myogenin expression levels
      required for viability, skeletal muscle development, and sternum formation.
AB  - The myogenic basic helix-loop-helix transcription factor myogenin plays an
      essential role in the differentiation of skeletal muscle and, secondarily, in rib
      and sternum formation during mouse development. However, virtually nothing is
      known about the quantitative requirements for myogenin in these processes. Here,
      we describe the generation of mice carrying a hypomorphic allele of myogenin,
      which expresses myogenin transcripts at approximately one-fourth the level of the
      wild-type myogenin allele. The hypomorphic allele in combination with wild-type
      and myogenin-null alleles was used to create an allelic series. Embryos
      representing the complete range of genotypes from homozygous wild type to
      homozygous null were analyzed for their viability, ability to form normal ribs
      and sternum, and extent of skeletal muscle differentiation. Embryos carrying the
      hypomorphic myogenin allele over a wild-type allele were normal. In embryos
      bearing homozygous hypomorphic alleles, the sternum developed normally and
      extensive skeletal muscle differentiation occurred. However, muscle hypoplasia
      and reduced muscle-specific gene expression were apparent in these embryos, and
      the mice were not viable as neonates. When the hypomorphic allele was placed over
      a myogenin-null allele, the resulting embryos had sternum defects resembling
      homozygous myogenin-null embryos, and there was severe muscle hypoplasia. Our
      results demonstrate that skeletal muscle formation is highly sensitive to the
      absolute levels of myogenin and that correct sternum formation, skeletal muscle
      differentiation, and viability each require distinct threshold levels of
      myogenin.

PMID- 10075841
TI  - The role of cell adhesion molecules in Drosophila heart morphogenesis: faint
      sausage, shotgun/DE-cadherin, and laminin A are required for discrete stages in
      heart development.
AB  - Heart development in the Drosophila embryo starts with the specification of
      cardiac precursors from the dorsal edge of the mesoderm through signaling from
      the epidermis. Cardioblasts then become aligned in a single row of cells that
      migrate dorsally. After contacting their contralateral counterparts, cardioblasts
      undergo a cytoskeletal rearrangement and form a lumen. Its simple architecture
      and cellular composition makes the heart a good system to study mesodermal
      patterning, intergerm layer signaling, and the function of cell adhesion
      molecules (CAMs) during morphogenesis. In this paper we focus on three adhesion
      molecules, faint sausage (fas), shotgun/DE-cadherin (shg/DE-Cad), and laminin A
      (lam A), that are essential for heart development. fas encodes an Ig-like CAM and
      is required for the correct number of cardioblasts to become specified, as well
      as proper alignment of cardioblasts. shg/DE-Cad is expressed and required at a
      later stage than fas; in embryos lacking this gene, cardioblasts are specified
      normally and become aligned, but do not form a lumen. Additionally, cardioblasts
      of shg mutant embryos show a redistribution of phosphotyrosine as well as a loss
      of Armadillo from the membrane, indicating defects in cell polarity. The shg
      phenotype could be phenocopied by applying EGTA or cytochalasin D, supporting the
      view that Ca2+-dependent adhesion and the actin cytoskeleton are instrumental for
      heart lumen formation. As opposed to cell-cell adhesion, cell-substrate adhesion
      mechanisms are not required for heart morphogenesis, but only for maintenance of
      the differentiated heart. Embryos lacking the lam A gene initially developed a
      normal heart, but showed twists and breaks of cardioblasts at late embryonic
      stages. We discuss our findings in light of recent results that elucidate the
      function of different adhesion systems in vertebrate heart development.

PMID- 10075842
TI  - Spatiotemporal characterization of intracellular Ca2+ rise during the acrosome
      reaction of mammalian spermatozoa induced by zona pellucida.
AB  - The mammalian sperm acrosome reaction (AR) is an essential event prior to sperm
      egg fusion at fertilization, and it is primarily dependent on an increase in
      intracellular Ca2+ concentration ([Ca2+]i). Spatiotemporal aspects of the [Ca2+]i
      increase during the AR induced by solubilized zona pellucida (ZP) in hamster
      spermatozoa were precisely investigated with a Ca2+ imaging technique using
      confocal laser scanning microscopy with two fluorescent Ca2+ indicators. A rapid
      rise in [Ca2+]i occurred immediately after the application of ZP solution through
      a micropipette. The rise was always initiated in the sperm head, even when the
      application was directed toward the tail. The elevated [Ca2+]i was little
      attenuated during measurement for 30-40 s. Acrosomal exocytosis was detected as a
      sudden decrease of fluorescence in the acrosomal vesicle approximately 20 s after
      the onset of the [Ca2+]i rise. High-resolution imaging revealed that the [Ca2+]i
      rise in the sperm head began at the region around the equatorial segment and
      spread over the posterior region of the head within 0.6 s, whereas Ca2+
      concentration in the acrosomal vesicle appeared to be unaltered. The [Ca2+]i rise
      was completely abolished under Ca2+-free extracellular conditions, indicating
      that it is totally attributable to Ca2+ influx. Nifedipine, an inhibitor of L
      type Ca2+ channels, did not affect the rising phase of the ZP-induced Ca2+
      response, but accelerated the decline of the [Ca2+]i rise and inhibited acrosomal
      exocytosis. The present study provides implicative information about the spatial
      organization of functional molecules involved in the signal transduction in
      mammalian AR.

PMID- 10075843
TI  - Activation of Xenopus eggs by proteases: possible involvement of a sperm protease
      in fertilization.
AB  - Egg activation in cross-fertilization between Xenopus eggs and Cynops sperm may
      be caused by a protease activity against Boc-Gly-Arg-Arg-MCA in the sperm
      acrosome. To determine the role of the sperm protease in fertilization, the
      protease was purified from Cynops sperm using several chromatographic techniques.
      We found that purified sperm protease readily hydrolyzes Boc-Gly-Arg-Arg-MCA and
      Z-Arg-Arg-MCA, that protease activity was inhibited by the trypsin inhibitors
      aprotinin and leupeptin, and that not only the purified protease, but also
      cathepsin B, induces activation in Xenopus eggs. We inseminated unfertilized
      Xenopus eggs with homologous sperm in the presence of various peptidyl MCA
      substrates or protease inhibitors and demonstrated that trypsin inhibitors or MCA
      substrates containing Arg-Arg-MCA reversibly inhibited fertilization of both
      fully jellied and denuded eggs. Sperm motility was not affected by the reagents.
      An extract obtained from Xenopus sperm showed hydrolytic activity against Boc-Gly
      Arg-Arg-MCA, Z-Arg-Arg-MCA, and Arg-MCA. These results suggest that the tryptic
      protease in Xenopus sperm is involved in fertilization, most likely by
      participating in egg activation.

PMID- 10075844
TI  - Development in the absence of skeletal muscle results in the sequential ablation
      of motor neurons from the spinal cord to the brain.
AB  - Mice lacking the transcription factors Myf-5 and MyoD lack all skeletal muscle
      and therefore present a unique opportunity to investigate the dependence of
      nervous system development on myogenesis. Motor neurons arose normally in the
      spinal cord of mutant embryos and by birth all somatic motor neurons were
      eliminated by apoptosis. By contrast, interneurons were not affected.
      Proprioceptive sensory neurons in the dorsal root ganglia underwent apoptosis.
      The facial motor nucleus was ablated of motor neurons and contained large numbers
      of apoptotic bodies. Surprisingly, giant pyramidal neurons were absent in the
      motor cortex without any corresponding evidence of apoptosis. The epaxial and
      cutaneous component of dorsal ramus failed to form in the absence of the myotome.
      Therefore, we conclude that nervous development is more intimately coupled to
      skeletal myogenesis than has previously been understood.

PMID- 10075845
TI  - Paracrine-mediated apoptosis in reproductive tract development.
AB  - In mammalian development, the signaling pathways that couple extracellular death
      signals with the apoptotic machinery are still poorly understood. We chose to
      examine Mullerian duct regression in the developing reproductive tract as a
      possible model of apoptosis during morphogenesis. The TGFbeta-like hormone,
      Mullerian inhibiting substance (MIS), initiates regression of the Mullerian duct
      or female reproductive tract anlagen; this event is essential for proper male
      sexual differentiation and occurs between embryonic days (E) 14 and 17 in the
      rat. Here, we show that apoptosis occurs during Mullerian duct regression in male
      embryos beginning at E15. Female Mullerian ducts exposed to MIS also exhibited
      prominent apoptosis within 13 h, which was blocked by a caspase inhibitor. In
      both males and females the MIS type-II receptor is expressed exclusively in the
      mesenchymal cell layer surrounding the duct, whereas apoptotic cells localize to
      the epithelium. In addition, tissue recombination experiments provide evidence
      that MIS does not act directly on the epithelium to induce apoptosis. Based on
      these data, we suggest that MIS triggers cell death by altering mesenchymal
      epithelial interactions.

PMID- 10075846
TI  - A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm
      induction.
AB  - Bone morphogenetic proteins (BMPs), members of the transforming growth factor
      beta superfamily, have been identified by their ability to induce cartilage and
      bone from nonskeletal cells and have been shown to act as a ventral morphogen in
      Xenopus mesoderm. We isolated a murine homeobox-containing gene, distal-less 5
      (mDlx5), as a BMP-inducible gene in osteoblastic MC3T3-E1 cells. Stable
      transfectants of MC3T3-E1 that overexpress mDlx5 mRNA showed increase in various
      osteogenic markers, a fourfold increase in alkaline phosphatase activity, a
      sixfold increase in osteocalcin production, and appearance in mineralization of
      extracellular matrix. Furthermore, mDlx5 was induced orthotopically in mouse
      embryos treated with BMP-4 and in fractured bone of adult mice. Consistent with
      these observations, we also found that injection of mDlx5 mRNA into dorsal
      blastomeres enhanced the ventralization of Xenopus embryos. These findings
      suggest that mDlx5 is a target gene of the BMP signaling pathway and acts as an
      important regulator of both osteogenesis and dorsoventral patterning of embryonic
      axis.

PMID- 10075847
TI  - Hoxa5 gene regulation: A gradient of binding activity to a brachial spinal cord
      element.
AB  - The Hox genes cooperate in providing positional information needed for spatial
      and temporal patterning of the vertebrate body axis. However, the biological
      mechanisms behind spatial Hox expression are largely unknown. In transgenic mice,
      gene fusions between Hoxa5 (previously called Hox-1.3) 5' flanking regions and
      the lacZ reporter gene show tissue- and time-specific expression in the brachial
      spinal cord in day 11-13 embryos. A 604-bp regulatory region with enhancer
      properties directs this spatially specific expression. Fine-detail mapping of the
      enhancer has identified several elements involved in region-specific expression,
      including an element required for expression in the brachial spinal cord. Factors
      in embryonic day 12.5 nuclear extracts bind this element in electrophoretic
      mobility shift assays (EMSA) and protect three regions from DNase digestion. All
      three sites contain an AAATAA sequence and mutations at these sites reduce or
      abolish binding. Furthermore, this element binds specific individual embryonic
      proteins on a protein blot. The binding activity appears as a gradient along the
      anterior-posterior axis with two- to threefold higher levels observed in extracts
      from anterior regions than from posterior regions. In parallel with the EMSA, the
      proteins on the protein blot also show reduced binding to probes with mutations
      at the AAATAA sites. Most importantly, transgenic mice carrying Hoxa5/lacZ
      fusions with the three AAATAA sites mutated either do not express the transgene
      or have altered transgene expression. The brachial spinal cord element and its
      binding proteins are likely to be involved in spatial expression of Hoxa5 during
      development.

PMID- 10075848
TI  - The ciD mutation encodes a chimeric protein whose activity is regulated by
      Wingless signaling.
AB  - The Drosophila cubitus interruptus (ci) gene encodes a sequence-specific DNA
      binding protein that regulates transcription of Hedgehog (Hh) target genes.
      Activity of the Ci protein is posttranslationally regulated by Hh signaling. In
      animals homozygous for the ciD mutation, however, transcription of Hh target
      genes is regulated by Wingless (Wg) signaling rather than by Hh signaling. We
      show that ciD encodes a chimeric protein composed of the regulatory domain of
      dTCF/Pangolin (Pan) and the DNA binding domain of Ci. Pan is a Wg-regulated
      transcription factor that is activated by binding of Armadillo (Arm) to its
      regulatory domain. Arm is thought to activate Pan by contributing a
      transactivation domain. We find that a constitutively active form of Arm
      potentiates activity of a CiD transgene and coimmunoprecipitates with CiD
      protein. The Wg-responsive activity of CiD could be explained by recruitment of
      the Arm transactivation function to the promoters of Hh-target genes. We suggest
      that wild-type Ci also recruits a protein with a transactivation domain as part
      of its normal mechanism of activation.

PMID- 10075849
TI  - Hox gene expression in limbs: colinearity by opposite regulatory controls.
AB  - Genes of the HoxD complex have a crucial role in the morphogenesis of vertebrate
      limbs. During development, their functional domains are colinear with their
      genomic positions within the HoxD cluster such that Hoxd13 and Hoxd12 are
      necessary for digit development, whereas Hoxd11 and Hoxd10 are involved in making
      forearms. Mutational analyses of these genes have demonstrated their importance
      and illustrated the requirement for a precise control of their expression during
      early limb morphogenesis. To study the nature of this control, we have scanned
      the posterior part of the HoxD complex with a targeted reporter transgene and
      analyzed the response of this foreign promoter to limb regulatory influences. The
      results suggest that this regulation is achieved through the opposite effects of
      two enhancer elements which would compete with each other for interacting with
      nearby-located promoters. The physical position of a given gene within this
      genomic interval of opposite regulations might thus determine its final
      expression pattern. This model provides a conceptual link between the morphology
      of the future limb and the genetic organization of the Hox gene cluster, a
      translation of a genomic context into a morphogenetic topology.

PMID- 10075850
TI  - Distinct neural stem cells proliferate in response to EGF and FGF in the
      developing mouse telencephalon.
AB  - Multipotent, self-renewing neural stem cells reside in the embryonic mouse
      telencephalic germinal zone. Using an in vitro neurosphere assay for neural stem
      cell proliferation, we demonstrate that FGF-responsive neural stem cells are
      present as early as E8.5 in the anterior neural plate, but EGF-responsive neural
      stem cells emerge later in development in a temporally and spatially specific
      manner. By separately blocking EGF and FGF2 signaling, we also show that EGF
      alone and FGF2 alone can independently elicit neural stem cell proliferation and
      at relatively high cell densities separate cell nonautonomous effects can
      substantially enhance the mitogen-induced proliferation. At lower cell densities,
      neural stem cell proliferation is additive in the presence of EGF and FGF2
      combined, revealing two different stem cell populations. However, both FGF
      responsive and EGF-responsive neural stem cells retain their self-renewal and
      multilineage potential, regardless of growth factor conditions. These results
      support a model in which separate, lineage-related EGF- and FGF-responsive neural
      stem cells are present in the embryonic telencephalic germinal zone.

PMID- 10075851
TI  - Evidence that a starfish egg Src family tyrosine kinase associates with PLC
      gamma1 SH2 domains at fertilization.
AB  - The initiation of calcium release at fertilization in the eggs of most animals
      relies on the production of IP3, implicating the activation of phospholipase C.
      Recent work has demonstrated that injection of PLC-gamma SH2 domain fusion
      proteins into starfish eggs specifically inhibits the initiation of calcium
      release in response to sperm, indicating that PLC-gamma is necessary for Ca2+
      release at fertilization [Carroll et al. (1997) J. Cell Biol. 138, 1303-1311].
      Here we investigate how PLC-gamma may be activated, by using the PLC-gamma SH2
      domain fusion protein as an affinity matrix to identify interacting proteins. A
      tyrosine kinase activity and an egg protein of ca. Mr 58 K that is recognized by
      an antibody directed against Src family tyrosine kinases associate with PLC-gamma
      SH2 domains in a fertilization-dependent manner. These associations are detected
      by 15 s postfertilization, consistent with a function in releasing Ca2+. Calcium
      ionophore treatment of eggs did not cause association of the kinase activity or
      of the Src family protein with the PLC-gamma SH2 domains. These data identify an
      egg Src family tyrosine kinase as a potential upstream regulator of PLC-gamma in
      the activation of starfish eggs.

PMID- 10075852
TI  - Influence of centriole behavior on the first spindle formation in zygotes of the
      brown alga Fucus distichus (Fucales, Phaeophyceae).
AB  - The influence of centrioles, derived from the sperm flagellar basal bodies, and
      the centrosomal material (MTOCs) on spindle formation in the brown alga Fucus
      distichus (oogamous) was studied by immunofluorescence microscopy using anti
      centrin and anti-beta-tubulin antibodies. In contrast to a bipolar spindle, which
      is formed after normal fertilization, a multipolar spindle was formed in
      polyspermic zygote. The number of mitotic poles in polyspermic zygotes was double
      the number of sperm involved in fertilization. As an anti-centrin staining spot
      (centrioles) was located at these poles, the multipolar spindles in polyspermic
      zygotes were produced by the supplementary centrioles. When anucleate egg
      fragments were fertilized, chromosome condensation and mitosis did not occur in
      the sperm nucleus. Two anti-centrin staining spots could be detected,
      microtubules (MTs) radiated from nearby, but the mitotic spindle was never
      produced. When a single sperm fertilized multinucleate eggs (polygyny), abnormal
      spindles were also observed. In addition to two mitotic poles containing anti
      centrin staining spots, extra mitotic poles without anti-centrin staining spots
      were also formed, and as a result multipolar spindles were formed. When karyogamy
      was blocked with colchicine, it became clear that the egg nucleus proceeded
      independently into mitosis accompanying chromosome condensation. A monoastral
      spindle could be frequently observed, and in rare cases a barrel-shaped spindle
      was formed. However, when a sperm nucleus was located near an egg nucleus, the
      two anti-centrin staining spots shifted to the egg nucleus from the sperm
      nucleus. In this case, a normal spindle was formed, the egg chromosomes arranged
      at the equator, and the associated MTs elongated from one pole of the egg spindle
      toward the sperm chromosomes which were scattered. From these results, it became
      clear that paternal centrioles derived from the sperm have a crucial role in
      spindle formation in the brown algae, such as they do during animal
      fertilization. However, paternal centrioles were not adequate for the functional
      centrosome during spindle formation. We speculated that centrosomal materials
      from the egg cytoplasm aggregate around the sperm centrioles and are needed for
      centrosomal activation.

PMID- 10075853
TI  - Identification of a novel cardiac lineage-associated protein(cCLP-1): A candidate
      regulator of cardiogenesis.
AB  - We describe the isolation and characterization of a cDNA clone, called cCLP-1,
      that is a candidate for the previously described early cardiac-specific
      transcription factor BBF-1. BBF-1 binds the MEF2 (or element B) binding site
      within the cardiac myosin light chain 2 (MLC2) gene promoter. We used the element
      B sequence as a probe to screen an expression library constructed from mRNA
      obtained from the presumptive heart-forming regions of stage 6 chicken embryos.
      This yielded the cCLP-1 cDNA clone. Gel-shift analysis of stage 6 embryonic
      chicken protein extracts suggests that a protein that is recognized by the anti
      cCLP-1 antibody binds to the same element B binding site to which BBF-1 binds.
      cCLP-1 mRNA was detected early in chicken development, prior to cardiac fate
      assignment at stage 4. The expression pattern of cCLP-1, based on whole mount in
      situ hybridization, coincides remarkably well with the established morphogenetic
      field of early heart formation. The nuclear localization of cCLP-1 is
      phosphorylation-dependent, suggesting that cCLP-1 may be a member of that class
      of transcription factors whose activity is regulated by cytoplasm to nucleus
      transport. Taken together, these data suggest that cCLP-1 may encode a novel
      transcription factor whose expression pattern is in agreement with that of the
      cardiogenic precursor cells of the early chicken embryo.

PMID- 10075854
TI  - A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a
      potent mesoderm inducer in Xenopus embryos.
AB  - The bone morphogenetic proteins (BMPs) play critical roles in patterning the
      early embryo and in the development of many organs and tissues. We have
      identified a new member of this multifunctional gene family, BMP-11, which is
      most closely related to GDF-8/myostatin. During mouse embryogenesis, BMP-11 is
      first detected at 9.5 dpc in the tail bud with expression becoming stronger as
      development proceeds. At 10.0 dpc, BMP-11 is expressed in the distal and
      posterior region of the limb bud and later localizes to the mesenchyme between
      the skeletal elements. BMP-11 is also expressed in the developing nervous system,
      in the dorsal root ganglia, and dorsal lateral region of the spinal cord. To
      assess the biological activity of BMP-11, we tested the protein in the Xenopus
      ectodermal explant (animal cap) assay. BMP-11 induced axial mesodermal tissue
      (muscle and notochord) in a dose-dependent fashion. At higher concentrations, BMP
      11 also induced neural tissue. Interestingly, the activin antagonist,
      follistatin, but not noggin, an antagonist of BMPs 2 and 4, inhibited BMP-11
      activity on animal caps. Our data suggest that in Xenopus embryos, BMP-11 acts
      more like activin, inducing dorsal mesoderm and neural tissue, and less like
      other family members such as BMPs 2, 4, and 7, which are ventralizing and anti
      neuralizing signals. Taken together, these data suggest that during vertebrate
      embryogenesis, BMP-11 plays a unique role in patterning both mesodermal and
      neural tissues.

PMID- 10075855
TI  - Drosophila Src42A is a negative regulator of RTK signaling.
AB  - The Src family of nonreceptor tyrosine kinases has been implicated in many signal
      transduction pathways. However, due to a possible functional redundancy in
      vertebrates, there is no genetic loss-of-function evidence that any individual
      Src family member has a crucial role for receptor tyrosine kinase (RTK)
      signaling. Here we show that an extragenic suppressor of Raf, Su(Raf)1, encodes a
      Drosophila Src family gene Src42A. Characterization of Src42A mutations shows
      that Src42A acts independent of Ras1 and that it is, unexpectedly, a negative
      regulator of RTK signaling. Our study provides the first evidence that Src42A
      defines a negative regulatory pathway parallel to Ras1 in the RTK signaling
      cascade. A possible model for Src42A function is discussed.

PMID- 10075856
TI  - Na+/H+ antiporter activity in hamster embryos is activated during fertilization.
AB  - This study characterized the activation of the regulatory activity of the Na+/H+
      antiporter during fertilization of hamster embryos. Hamster oocytes appeared to
      lack any mechanism for the regulation of intracellular pH in the acid range.
      Similarly, no Na+/H+ antiporter activity could be detected in embryos that were
      collected from the reproductive tract between 1 and 5 h post-egg activation
      (PEA). Activity of the Na+/H+ antiporter was first detected in embryos collected
      at 5.5 h PEA and gradually increased to reach maximal activity in embryos
      collected at 7 h PEA. Parthenogenetically activated one-cell and two-cell embryos
      demonstrate Na+/H+ antiporter activity, indicating that antiporter activity is
      maternally derived and initiated by activation of the egg. The inability of
      cycloheximide, colchicine, or cytochalasin D to affect initiation of antiporter
      activity indicates that antiporter appearance is not dependent on the synthesis
      of new protein or recruitment of existing protein to the cell membrane. In
      contrast, incubation of one-cell embryos with sphingosine did inhibit the
      appearance of Na+/H+ antiporter activity, showing that inhibition of normal
      protein kinase C activity is detrimental to antiporter function. Furthermore,
      incubation of oocytes with a phorbol ester which stimulates protein kinase C
      activity induced Na+/H+ antiporter activity in oocytes in which the activity was
      previously absent. Incubation with an intracellular calcium chelator also reduced
      the appearance of antiporter activity. Taken together, these data indicate that
      the appearance of Na+/H+ antiporter activity following egg activation may be due,
      at least in part, to regulation by protein kinase C and intracellular calcium
      levels.

PMID- 10075857
TI  - The effects of environmental and other chemicals on the human immune system: the
      emergence of immunotoxicology.

PMID- 10075858
TI  - Activation of the human RANTES gene promoter in a macrophage cell line by
      lipopolysaccharide is dependent on stress-activated protein kinases and the
      IkappaB kinase cascade: implications for exacerbation of allergic inflammation by
      environmental pollutants.
AB  - Macrophages are targeted by environmental pollutants and play a role in allergic
      inflammation. We explored the molecular basis for induction of RANTES (regulated
      upon activation, normal T-cells expressed and secreted) mRNA by
      lipopolysaccharide (LPS) and the redox-active quinone, tert-butylhydroxyquinone
      (tBHQ). We demonstrate that transcriptional activation of the human RANTES
      promoter by LPS is dependent on specific AP-1 and NF-kappaB response elements,
      which are regulated by c-Jun N-terminal kinase (JNK) and NF-kappaB kinase
      cascades, respectively. The transcriptional activation of the TRE3/4 site is
      mediated through the transcriptional activation of c-Jun by JNK. A c-Jun mutant
      which lacks a transcriptional activation domain interfered in the activation of
      the RANTES promoter. Similarly, kinase-inactive NF-kappaB inducing kinase
      interfered in the activation of the RANTES promoter. While activation of the
      RANTES promoter could also be blocked by the downstream kinase-inactive IkappaB
      kinases, only IKKalpha appears to be LPS-inducible. tBHQ also exerted subtle
      effects on the human RANTES promoter and induced mRNA expression in parallel with
      generating NF-kappaB shift complexes.

PMID- 10075859
TI  - Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV.
AB  - Examination of annexin V binding, an indicator of early apoptosis, on lymphocytes
      from HIV+ people immediately after isolation showed that both CD4(+) and CD8(+) T
      cells were apoptotic, whereas B cell apoptosis was induced mainly after
      incubation. CD8(+) T cell apoptosis correlated with fewer CD4(+) T cells, but not
      the level of viremia. To determine potential mechanisms for apoptosis, we
      examined FasL expression, which was dramatically elevated on CD14(+) monocytes;
      however, antibody to FasL did not reproducibly inhibit apoptosis. Rather, CD8(+)
      T cell apoptosis was caused by antigen-presenting cells because removal of
      monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell
      apoptosis also involved costimulatory signals delivered by T cells but not
      monocytes. A unique CD8(bright)CD28(dim) T cell population died after
      costimulation by monocytes. Because this population was increased in patients
      with undetectable viremia, abnormal antigen-presenting cells may contribute to
      continued CD8(+) T cell exhaustion by inducing apoptosis.

PMID- 10075860
TI  - Effect of topical fluticasone propionate on the mucosal allergic response induced
      by ragweed allergen and diesel exhaust particle challenge.
AB  - Glucocorticoids block the local allergic response in a variety of ways. However,
      studies have also shown that glucocorticoids increase in vitro IgE synthesis and
      that treatment with corticosteroids may result in elevated serum IgE
      concentrations. The ability of topical glucocorticoids to modulate the mucosal
      IgE response has not been elucidated. We studied the effect of topical steroid
      (fluticasone propionate) treatment on the local allergic antibody response
      induced by challenge with either allergen or diesel exhaust particles (DEP). A
      parallel group study was performed with ragweed-allergic subjects, each subject
      serving as his/her own control. Nasal provocation challenges were performed on
      three groups. One group received ragweed allergen, another diesel exhaust
      particles, and the third saline. The study was repeated following 1 week of
      treatment with intranasal fluticasone propionate. Each group received the same
      challenge as before. The concentrations of total immunoglobulins (IgE, IgG, IgA,
      and IgM), anti-ragweed antibody, IgE- and IgA-secreting cells, epsilon (epsilon)
      mRNA, and cytokine mRNAs (IL-2, -4, -5, -6, TNF-alpha, INF-gamma) were measured
      in nasal lavages performed before and at various time points after challenge.
      Treatment with fluticasone propionate for 7 days caused a decrease in the
      concentrations of nasal IgE protein, IgE-producing cells, total epsilon mRNA, and
      all the cytokine mRNAs tested. Furthermore, treatment with fluticasone propionate
      inhibited the production of allergen-specific IgE and cytokine mRNAs following
      challenge with ragweed antigen. However, fluticasone treatment did not
      significantly inhibit the enhancement of mucosal IgE production or cytokine mRNAs
      observed following nasal challenge with DEP. These results indicate that 1-week
      treatment with topical fluticasone propionate was effective in blocking local
      effects of allergen exposure but was unable to inhibit the adjuvant-like effect
      of DEP.

PMID- 10075861
TI  - Novel phenotype associated with in vivo activated CTL precursors.
AB  - A previously undefined phenotype of CD8(+) cells that appears to represent in
      vivo activated CTL precursors (CTLP*) has been identified in the spleens of
      C57Bl/6 mice responding to a P815 tumor allograft. This population was first
      evident by the transient expression of very high levels of CD28 and CD44 on day 5
      of the allograft response and reached maximal levels on days 7 and 8 before
      declining on day 9. A transient increase in CD69 expression was also observed on
      these cells on day 5. In contrast, CTL effectors (CTLE), identified by their
      CD8(+)CD44(hi)CD62LloCD45RBlo phenotype, were not appreciably detected in the
      spleen until day 8 and reached maximal levels on day 10. Further characterization
      of CTLP* on day 7 revealed that they represented blasting cells by increased
      light scatter and also expressed very high levels of CD54 but not CD122, CD152,
      or CD154. In addition, the cells had already up-regulated CD49d, asialo GM1,
      CD11a, and CD95L, and down-regulated their expression of CD62L. A small
      percentage of these cells also expressed CD25. Day 7 CTLP* sorted on the basis of
      their CD44(xhi) and CD54(xhi) phenotype did not exhibit cytolytic activity in a
      standard chromium release assay but became cytotoxic when they were cultured in
      the presence of exogenous murine IL-2 for 5 days. Granzyme B activity, however,
      was detected in CTLP* on day 7 at levels equivalent to CTLE on day 10. In order
      to establish a potential precursor relationship between CTLP* and CTLE, mice were
      treated with various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a
      chemical that has been shown to dose-dependently suppress the in vivo generation
      of CTLE to P815 tumor cells by altering an early stage of CTLP activation.
      Results indicated that CTLP* were suppressed by TCDD on day 7 to the same degree
      that CTLE were suppressed on day 10. Importantly, for controls and for all doses
      of TCDD, there were approximately 12.5 CTLE on day 10 for every CTLP* detected on
      day 7. These results suggested that TCDD acted identically across all doses to
      inhibit the early stages of activation of CTLP but did not affect the final
      stages of differentiation and expansion to CTLE. This interpretation supports the
      previous observation that TCDD exposure had to occur within the first 3 days of
      the allograft response in order to induce suppression of CTLE activity. Taken
      together, these results support the conclusion that in vivo activated CTLP can be
      identified by their unique expression of very high levels of CD44, CD28, and/or
      CD54 prior to their full maturation and clonal expansion to functional CTLE.

PMID- 10075862
TI  - The effect of anti-gp39 treatment on the intestinal manifestations of acute
      murine graft-versus-host disease.
AB  - The changes in the intestinal morphology of murine T-cell-mediated acute semi
      allogenic graft-versus-host disease (GvH) are characterized by lymphocytic
      infiltrates, crypt hyperplasia, and villous atrophy. In the present study, the
      role of CD40L (gp39)-an important member of the TNF/NGF superfamily of receptors
      and their ligands-for T-cell costimulation in vivo during the development of
      mucosal atrophy was investigated. We found that the inhibition of the CD40L-CD40
      interaction in GvH animals by the administration of an anti-CD40L antibody (MR-1)
      completely prevents the development of crypt hyperplasia and villous atrophy in
      GvH animals. This includes a normalization of the rate of crypt cell apoptosis,
      which is augmented in untreated GvH animals. In conclusion, the CD40L-CD40
      interaction is crucial in the pathogenesis of T-cell-mediated mucosal atrophy.

PMID- 10075863
TI  - Selection of hprt mutant T cells as surrogates for dividing cells reveals a
      restricted T cell receptor BV repertoire in insulin-dependent diabetes mellitus.
AB  - T cells with somatically acquired mutations in the hypoxanthine-guanine
      phosphoribosyltransferase (hprt) gene were isolated from patients with insulin
      dependent diabetes mellitus (IDDM) as representatives of populations potentially
      enriched for in vivo activated T cells. TCRB gene V region usage among mutant
      isolates from individual IDDM patients, but not from normal controls, showed a
      pronounced preference for BV14 and, to a lesser extent, BV6. Wild-type
      (nonmutant) isolates did not show such preferences. Extensive in vivo clonal
      expansions of the BV14 expressing mutant T cells from IDDM patients were revealed
      by sequence identity of TCRB chain junctional regions. These data support
      restricted TCRB gene usage in T cell populations enriched for in vivo activated
      clones in patients with IDDM.

PMID- 10075864
TI  - Autoantibodies to leukocyte alphaMbeta2 integrin glycoproteins in HIV infection.
AB  - HIV infection is often associated with polyclonal B-cell activation,
      autoantibodies, and clinically evident autoimmune disease. Because neutropenia
      and anti-neutrophil autoantibodies are common clinical features of HIV disease,
      we studied a series of HIV+ patients to determine whether anti-alphaMbeta2
      integrin (MAC-1) specific anti-neutrophil autoantibodies occur in HIV disease, as
      we have shown to occur in patients with immune neutropenia not associated with
      HIV. Two new assays specific for anti-alphaMbeta2 IgG were developed to carry out
      these studies: an ELISA method using affinity-purified alphaMbeta2 integrin
      protein, and a flow cytometry method using subclones of the 293 human fetal
      kidney cell line, stably transfected with cDNAs for the alphaM and/or beta2
      integrin subunits. In studies of the sera of 20 untreated HIV+ individuals, anti
      alphaMbeta2 activity was detected in 9 (45%) by one or the other of these assays
      and in 5 (25%) by both assays. Seven of the 20 HIV+ study subjects had
      unexplained neutropenia, and of these, 6 (86%) were positive for anti-alphaMbeta2
      autoantibodies. Our findings indicate that anti-alphaMbeta2 integrin
      autoantibodies are frequent in HIV+ individuals, particularly when unexplained
      neutropenia is also present, and raise the possibility that these autoantibodies
      may have a role in the acquired neutrophil dysfunction and increased risk of
      nonopportunistic bacterial infections observed in HIV disease.

PMID- 10075865
TI  - The receptor for the globular "heads" of C1q, gC1q-R, binds to fibrinogen/fibrin
      and impairs its polymerization.
AB  - The 33-kDa cellular C1q binding protein, designated gC1q-R was previously shown
      to bind a number of plasma proteins involved in the coagulation and kinin
      systems. This study demonstrates the interaction between recombinant gC1q-R and
      fibrinogen. Using enzyme-linked immunosorbent assays, biotinylated gC1q-R was
      found to bind to microplate-immobilized fibrinogen in a manner which was specific
      and inhibited by excess soluble fibrinogen or polyclonal antibodies directed
      against either gC1q-R or fibrinogen. Moreover, gC1q-R inhibited fibrin
      polymerization in a dose-dependent manner. Reptilase induced fibrin clot
      formation was completely inhibited by gC1q-R at a 2:1 molar ratio (gC1q
      R:fibrinogen), and repolymerization of thrombin induced fibrin monomers was
      similarly abrogated. At equivalent molar concentrations, gC1q-R appeared to be a
      more potent inhibitor of fibrin polymerization than fibrinogen, a well-known
      inhibitor. Moreover, in the presence of both gC1q-R and soluble fibrinogen, the
      effect of each inhibitor on fibrin polymerization was additive. When plasmin
      derived fibrinogen degradation products, including the C-terminal D domain (D
      100) or the N-terminal E domain, were immobilized on microtiter plates, gC1q-R
      bound to fibrinogen fragment D-100, but not to fragment E. Further digestion of
      fibrinogen fragment D-100 by plasmin to fragment D-60 resulted in loss of gC1q-R
      binding. Thus, gC1q-R binds to the D domain of fibrinogen/fibrin, and the
      carboxyterminal segment of at least the fibrinogen/fibrin gamma chain appears
      important for this interaction. These observations may suggest a potential role
      for gC1q-R in modulating fibrin formation particularly at local sites of immune
      injury or inflammation.

PMID- 10075866
TI  - Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause
      and unexplained infertility than in the general population.
AB  - The objective of this study was to: (1) assess the relative prevalence of
      ovarian, thyroid, nuclear, and cardiolipin antibodies associated with premature
      menopause and unexplained infertility and (2) compare ovarian and thyroid
      antibodies in premature menopause, unexplained infertility, and the general
      population. Autoantibodies were evaluated in women with premature menopause (n =
      30), unexplained infertility with (n = 38) or without (n = 15) prior gonadotropin
      induced ovulation, and normal cycling controls (n = 12) and in a population of
      women obtained from a blood bank (n = 53). Antibodies to ovary (OVAB), thyroid
      (THYAB; thyroid peroxidase and thyroglobulin), cardiolipin, and eight nuclear
      antigens were assessed by enzyme immunoassay. Organ-specific antibodies (ovary
      and thyroid) were present with significantly greater frequency than non-organ
      specific antibodies (nuclear and cardiolipin) in premature menopause and
      unexplained infertility (60% (50/83) vs 16% (13/83) respectively; P < 0.0001).
      OVAB (53%, 44/83) were significantly more frequent than THYAB (30%, 25/83) in
      premature menopause and unexplained infertility (P = 0.0030). THYAB did not
      differ among all groups (P = 0.78). In premature menopause and treated or
      untreated unexplained infertility OVAB frequencies were 53, 61, and 33%,
      respectively, and were significantly more frequent than in the population (17%)
      (P = 0.0001). In unexplained infertility, individuals with no prior gonadotropin
      induced ovulation had a lower frequency of OVAB than treated individuals (P =
      0.07). The frequency distribution of optical density values for OVAB was
      significantly higher for premature menopause and unexplained infertility than for
      population or normal cycling women (P < 0.0001). Thus, only ovarian antibodies
      were significantly more frequent than other antibody markers of autoimmunity in
      premature menopause and unexplained infertility.

PMID- 10075867
TI  - Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic
      drugs.
AB  - Macrophage Fcgamma receptors have an important role in host defense and the
      pathophysiology of immune mediated disorders. Alteration of splenic macrophage
      Fcgamma receptors expression predisposes to severe infection. Inhibition or
      blockade of splenic macrophage Fcgamma receptors is one of the mechanisms by
      which immune cytopenias improve. Dopaminergic drugs have clinically significant
      regulatory functions on the immune response. Using an experimental model in the
      guinea pig we assessed the effect of commonly used dopaminergic drugs on the
      expression of macrophage Fcgamma receptors. Three dopa-antagonists,
      bromocryptine, leuprolide, and pergolide, and seven dopa-antagonists,
      chlorpromazine, SCH 23390, metochlopramide, sulpiride, veralipride, alizapride,
      and cisapride, were studied. Following guinea pig treatment with dopaminergic
      drugs, the clearance of IgG-sensitized RBCs in vivo, the in vitro binding of IgG
      sensitized RBCs by isolated splenic macrophages and flow cytometry with
      monoclonal antibodies were performed. Treatment with dopa-agonists enhanced the
      clearance of IgG-sensitized RBCs, the in vitro binding of IgG-sensitized RBCs by
      isolated splenic macrophages, and the cell surface expression of both macrophage
      Fcgamma receptors, and vice versa, dopa-antagonists impaired macrophage Fcgamma
      receptors expression. Macrophage FcgammaR1,2 was more sensitive than FcgammaR2 to
      such dopaminergic effect. These alterations of macrophage Fcgamma receptors
      expression are mediated by both D1 and D2 dopamine receptors, with a major
      participation of D2 receptors. Dopaminergic drugs alter the clearance of IgG
      coated cells by an effect at the expression of splenic macrophage Fcgamma
      receptors.

PMID- 10075868
TI  - Thymic microenvironment and NZB mice: the abnormal thymic microenvironment of New
      Zealand mice correlates with immunopathology.
AB  - There are distinct microenvironmental abnormalities of thymic architecture in
      several murine models of SLE defined using immunohistochemistry and a panel of
      mAb dissected at thymic epithelial markers. To address the issue of the
      relationship between the thymic microenvironment and autoimmunity, we studied
      backcross (NZB x NZW) F1 x NZW mice in which 50% of offspring develop nephritis
      associated with proteinuria and anti-DNA antibodies. We reasoned that if thymic
      abnormalities are associated with development of disease, the correlation of
      abnormalities with lupus-like disease in individual backcross mice will form the
      foundation for identification of the mechanisms involved. In parallel, we
      directed a genetic linkage analysis, using markers previously shown to be linked
      to nephritis and IgG autoantibody production, to determine if such loci were
      similarly associated with microenvironmental changes. Our data demonstrate that
      all (NZB x NZW) F1 x NZW backcross mice with disease have microenvironmental
      defects. Although the microenvironmental defects are not sufficient for
      development of autoimmune disease, the severity of thymic abnormalities
      correlates with titers of IgG autoantibodies to DNA and with proteinuria.
      Consistent with past studies of (NZB x NZW) F1 x NZW mice, genetic markers on
      proximal chromosome 17 (near MHC) and distal chromosome 4 showed trends for
      linkage with nephritis. Although the markers chosen only covered about 10-15% of
      the genome, the results demonstrated trends for linkage with thymic medullary
      abnormalities for loci on distal chromosome 4 and distal chromosome 1. We believe
      it will be important to define the biochemical nature of the molecules recognized
      by these mAbs to understand the relationships between thymic architecture and
      immunopathology.

PMID- 10075869
TI  - Structural relationship of lambda-type light chains with AL amyloidosis.
AB  - Three human amyloidogenic Bence Jones proteins, NIG76 VlambdaII, NIG204 VlambdaI,
      and NIG250 VlambdaV, were characterized. In a comparative study, three amino
      acids, Ser-25a, Thr-68, and Val-95, were found to be common to amyloidogenic
      proteins of the VlambdaII subgroup. NIG204 had an insertion of Pro residue
      following position 30 (30a). Proteins having an insertion at this position are
      invariantly amyloidogenic. NIG250 had a characteristic VlambdaV VL domain, with
      Mcg+ and KERN+ CL domain isotypes. Following the protein DEL, this is the second
      example of this subgroup. No common residue is found in the other subgroup
      proteins but unique substitutions do occur. It would seem that any substitution
      that causes an alteration in the protein conformation may lead to its being more
      prone to association with the amyloid processes.

PMID- 10075870
TI  - Aspergillus fumigatus antigen exposure results in pulmonary airway resistance in
      wild-type but not in IL-4 knockout mice.
AB  - Inhalation of Aspergillus fumigatus, a ubiquitous fungus, results in the
      development of allergic bronchopulmonary aspergillosis, a disabling allergic lung
      disease. For better patient management early diagnosis is essential, and
      understanding of the immune mechanism is important in achieving this goal.
      Although animal model studies have contributed to the understanding of the
      disease mechanism, details on the immunopathogenesis are still lacking. In the
      present study, we have developed an allergic aspergillosis model in wild-type and
      IL-4 knockout mice and studied the immune and airway responses. The results
      indicate that the immune response, pulmonary pathology, and airway reactivity
      comparable to allergic bronchopulmonary aspergillosis are reproducible in wild
      mice. IL-4 knockout mice showed similar pulmonary pathology, but no increase in
      airway resistance, suggesting that IgE and hence IL-4 may be important in
      eliciting the airway response, while other factors may be involved in the
      inflammatory process.

PMID- 10075871
TI  - Hydrolysis of peripheral leucine enkephalin in allergic asthma.
AB  - Plasma hydrolysis of leucine enkephalin was studied in a group of patients
      affected by seasonal allergic asthma in acute and quiescent stage; data were
      compared with those obtained from a control group of healthy volunteers. Results
      obtained indicate a statistically significant reduction of leu-enkephalin
      hydrolysis in allergic subjects. In the quiescent stage, substrate degradation is
      reduced, and the pattern of the hydrolysis by-products is modified with respect
      to normal controls. In the acute stage, hydrolysis is further reduced, and the
      pattern of the hydrolysis by-products is further modified with respect to the
      quiescent stage. The variations of leu-enkephalin hydrolysis appear to be
      controlled by decreased activity of proteolytic enzymes and by increased activity
      of the low-molecular-weight plasma inhibitors active on these enzymes. The sum of
      these processes is conducive to a distribution of enkephalin-hydrolyzing enzymes,
      as well as a hydrolysis pattern, that appears to be specific for the allergic
      subjects and distinct from that seen in the controls.

PMID- 10075872
TI  - Production of TNF-alpha by murine bone marrow derived mast cells activated by the
      bacterial fimbrial protein, FimH.
AB  - Production of tumor necrosis factor alpha (TNF-alpha) by mast cells is an
      important aspect of host defense against gram negative bacteria. In order to
      define the intracellular pathways utilized by mast cells in this physiological,
      protective role, we have studied the production of TNF-alpha in bone marrow
      derived mast cells from the C3H/HeJ (LPS-insensitive) strain following exposure
      to bacteria expressing the fimbrial protein, FimH. Mast cells exposed to FimH
      produce TNF-alpha (300-1200 pg/10(6) cells) over 1-3 h compared with 1800-15,000
      pg/10(6) cells produced by cells triggered via IgE/antigen. This low level of TNF
      alpha production in vitro is compatible with the protective in vivo role of mast
      cells to produce modest amounts of TNF-alpha in contrast to the large amounts of
      mediators released during maximal activation. A second difference between the two
      signals is sensitivity to cyclosporin A (CsA). The IgE/antigen pathway is
      inhibited by 90-95% at 0.02 to 0.5 microM cyclosporin A whereas the FimH pathway
      is inhibited by only 40%. These data demonstrate that the intracellular pathway
      activated by FimH is different from that activated by IgE/antigen both in terms
      of amount of TNF-alpha produced and in sensitivity to CsA. This is the first
      evidence that FimH activates mast cells via a pathway that is distinct from that
      used by IgE/antigen.

PMID- 10075873
TI  - Detection of intracellular phosphorylated STAT-1 by flow cytometry.
AB  - We have applied flow cytometry to the investigation of interferon-gamma
      activation of human monocytes. This approach uses monoclonal antibodies that
      distinguish between the native and phosphorylated forms of STAT-1. It enables
      rapid and quantitative assessment of STAT-1 phosphorylation on a discrete cell
      basis and is both more sensitive and less time consuming than immunoblotting.
      Furthermore, it allows for discrimination between a mixture of cells that differ
      in their response to interferon-gamma. This approach should allow for the
      evaluation of different intracellular signaling pathways using a combination of
      monoclonal reagents that are specific for native and activation modified
      proteins. Application of this form of testing should prove valuable in screening
      for signaling defects in selected patients with recurrent infections. In
      addition, this technique should permit dissection of a full range of cellular
      signaling pathways at the protein level.

PMID- 10075874
TI  - Abstracts presented for the 14th annual conference on clinical immunology and 5th
      international symposium on clinical immunology 

PMID- 10075875
TI  - Second joint meeting of the clinical immunology society and the clinical
      immunology committee of the international union of immunological societies 

PMID- 10075876
TI  - Tools for turnover: methods for analysis of mRNA stability in eukaryotic cells.

PMID- 10075877
TI  - Analysis of mRNA decay pathways in Saccharomyces cerevisiae.
AB  - The analysis of mRNA turnover often requires a knowledge of the pathway by which
      a particular mRNA is being degraded. In this article we describe experimental
      procedures that can be used to determine the mechanism of degradation for yeast
      transcripts. These approaches include the insertion of strong secondary
      structures to block exonuclease cleavage and thereby trap decay intermediates. In
      addition, mRNA decay pathways can be analyzed by using regulatable promoters to
      perform transcriptional pulse-chase experiments, thereby allowing the
      determination of precursor-product relationships during the mRNA decay process.
      Finally, the mechanism of mRNA degradation can also now be determined by using
      trans-acting mutations specific for distinct mRNA turnover pathways. Most
      importantly, the combination of these three approaches can often clearly define
      the mechanism(s) by which a given transcript is degraded.

PMID- 10075878
TI  - Transcriptional pulsing approaches for analysis of mRNA turnover in mammalian
      cells.
AB  - Modulation of mRNA stability provides a powerful means for controlling gene
      expression during the cell cycle, cell differentiation, the immune response, as
      well as many other physiological transitions. Through the years, many different
      methods have been developed for measuring mRNA stability. Frequently mRNA
      stability is studied indirectly by analyzing the steady-state level of mRNA.
      Therefore by inference, changes in mRNA abundance are thought to affect only the
      stability of the mRNA, an assumption that is not always correct. Alternatively,
      direct measurements of mRNA decay are performed in a number of ways, including
      kinetic labeling techniques and administration of transcriptional inhibitors. Due
      to the nature of these techniques, they either are technically demanding or
      introduce a significant change in cell physiology. In addition, many critical
      mechanistic issues as to deadenylation kinetics, decay intermediates, and
      precursor-product relationships cannot be readily addressed by these methods.
      Here, we describe and discuss in detail two different transcriptional pulsing
      methods based on the c-fos serum-inducible promoter and the tetracycline
      regulated promoter systems as an effort to better elucidate the mechanistic steps
      and regulation underlying differential and selective mRNA turnover in mammalian
      cells. Both systems allow unequivocal monitoring of deadenylation and decay
      kinetics as well as determination of precursor-product relationship. In addition,
      decay rate constants and half-lives are determined and used in both methods to
      quantitatively denote the mRNA stability. Thus, they provide a reliable way to
      determine subtle yet physiologically meaningful changes in mRNA stability.
      Application of one method or the other covers the study of mRNA turnover in most
      mammalian cell types under a wide range of physiological conditions.

PMID- 10075879
TI  - An in vitro system using HeLa cytoplasmic extracts that reproduces regulated mRNA
      stability.
AB  - The pathways and machinery involved in the regulated turnover of mRNAs in
      mammalian cells are largely unknown. We have developed an in vitro system using
      HeLa cytoplasmic S100 extracts and exogenous polyadenylated RNA substrates that
      faithfully reproduces in vivo aspects of regulated mRNA turnover. RNA substrates
      for use in the system that contain a poly(A) tail precisely at their 3' end can
      be readily prepared using a ligation-polymerase chain reaction approach. The
      system also uses standard cytoplasmic S100 extracts that are activated through
      the sequestration of poly(A)-binding proteins by the addition of cold poly(A)
      RNA. On incubation in the system, the poly(A) tail is removed from RNA substrates
      by a sequence-specific deadenylase activity and the body of the transcript is
      ultimately degraded in the system with no apparent intermediates by an ATP
      dependent ribonulceolytic activity. AU-rich destability elements can regulate the
      rates of both deadenylation and degradation in the system. This in vitro system,
      therefore, should allow the elucidation of pathways of mRNA turnover,
      identification of the cellular factors involved, and insights into the mechanisms
      that regulate the half-life of a mRNA.

PMID- 10075880
TI  - Linking mRNA turnover and translation: assessing the polyribosomal association of
      mRNA decay factors and degradative intermediates.
AB  - mRNA decay is a multistep process, often dependent on the active translation of
      an mRNA and on components of the translation apparatus. In Saccharomyces
      cerevisiae, several trans-acting factors required for mRNA decay associate with
      polyribosomes. We have explored the specificity of the interactions of these
      factors with polyribosomes, using sucrose gradient sedimentation analysis of the
      yeast UPF1 protein to test whether such interactions are altered when
      polyribosomes are disrupted by treatment with EDTA, digestion with micrococcal
      nuclease, or shifting of cells containing a temperature-sensitive eIF3 mutation
      to the nonpermissive temperature. These experiments, as well as others assaying
      the strength of factor association in high-salt sucrose gradients, lead us to
      conclude that Upf1p is tightly bound to the smallest polyribosomes, but not to
      the 40S or 60S ribosomal subunits. Similar experimental approaches were used to
      determine whether mRNA decay initiates prior to mRNA release from polyribosomes.
      Using sucrose gradient fractionation and Northern blotting, we can detect the
      polysomal association of a PGK1 mRNA decay intermediate and conclude that mRNA
      decay commences while an mRNA is still being translated.

PMID- 10075881
TI  - Assaying the polyadenylation state of mRNAs.
AB  - The poly(A) tail present at the 3' end of most eukaryotic mRNAs can play a
      critical role in message translation and stability. Therefore, identifying
      alterations in poly(A) tail length can yield important insights into an mRNA's
      function and subsequent physiological impact. Here, we present three methods for
      assaying polyadenylation of a specific mRNA in the context of total cellular RNA.
      The first method described, oligo(dT)/RNase H-Northern analysis, is the classic
      labor-intensive assay for polyadenylation and is included for historical
      reference and as a potential experimental control for the poly(A) test (PAT)
      assays described subsequently. The PAT methods-rapid amplification of cDNA ends
      PAT (RACE-PAT), and ligase-mediated PAT (LM-PAT)-are polymerase chain reaction
      driven assays that allow speed, sensitivity, and length quantitation. The PAT
      assays can be conducted in a single day and can readily detect the poly(A) status
      of an mRNA present in subnanogram quantities of total cellular RNA.

PMID- 10075882
TI  - Monitoring mRNA decapping activity.
AB  - mRNA decapping is a common step shared between two important mRNA decay pathways
      in yeast, Saccharomyces cerevisiae. To investigate how mRNAs are decapped, we
      have developed an assay that can be easily used to measure the decapping
      activity. This assay has been used to isolate yeast strains with altered
      decapping activities. The results demonstrated that decreased decapping activity
      in vitro corresponds well with the decapping-deficient phenotype in vivo. This
      assay has been applied to the purified yeast decapping enzyme Dcp1 protein as
      well as crude yeast extracts and Xenopus oocyte extracts.

PMID- 10075883
TI  - Assays for analyzing exonucleases in vitro.
AB  - Ribonucleases play essential roles in cell growth, differentiation, and the
      response to stress. This article deals with exoribonucleases, enzymes that
      degrade RNAs beginning at either the 5' or 3' end and proceed down the length of
      the RNA. The preparation of a crude extract of a mammalian 3'-to-5' exonuclease
      is described. Assay conditions for both 5'-to-3' and 3'-to-5' exonucleases are
      given. One of these is a yeast enzyme that is known to be involved in mRNA decay.
      Others are vertebrate exonucleases that are presumed to have a role in mRNA
      stability but have not yet been proven to do so.

PMID- 10075884
TI  - Characterization of mRNA endonucleases.
AB  - Endonucleases are key effectors of mRNA degradation, particularly for mRNAs whose
      turnover rates are regulated by extracellular stimuli. The rapid clearance of
      mRNA degradation products in vivo and the need to selectively identify mRNA
      endonucleases in the presence of many other cellular ribonucleases make the study
      of these enzymes particularly challenging. We have successfully purified and
      cloned one such enzyme, termed polysomal RNase 1, or PMR-1. Presented here are
      protocols either developed in our laboratory or adapted from the work of others
      that we have used successfully in characterizing PMR-1. We first describe methods
      to determine whether a particular mRNA is degraded in vivo through an
      endonuclease-initiated mechanism, and then present approaches for developing an
      in vitro mRNA degradation system. Next we describe experiments one should perform
      to optimize reaction conditions, determine cofactor requirements for an
      endonuclease, map in vitro cleavage sites, and characterize endonucleolytic
      cleavage products. Finally we describe kinetic parameters one should evaluate in
      characterizing the enzymology of mRNA endonucleases, with particular concern
      focused on the relative selectivity of these enzymes for cleavage at preferred
      sites within target mRNAs.

PMID- 10075885
TI  - Identification and characterization of proteins binding A + U-rich elements.
AB  - A + U-Rich elements (AREs) have been extensively investigated as cis-acting
      determinants of rapid mRNA turnover. Recently, a number of RNA-binding proteins
      interacting with AREs have been described. This article presents strategies and
      techniques used by our laboratory to identify and characterize a family of ARE
      binding proteins collectively termed AUF1. However, these techniques may be
      applied to the study of any protein displaying sequence-specific RNA binding
      activity. The techniques described here include the purification of native AUF1
      from cultured cells as well as the preparation of recombinant AUF1 proteins using
      a bacterial expression system. Analyses of RNA-protein interactions are also
      described, including the use of gel mobility shift assays with synthetic RNA
      probes to monitor specific RNA binding activity in cell extracts or with
      recombinant proteins. Variations of this technique are also described to evaluate
      the RNA binding affinity of recombinant proteins and the use of specific RNA
      competitors to assess RNA determinants of protein binding specificity. Other
      techniques presented include the identification of specific proteins in
      RNA:protein complexes using antibody supershifts and the estimation of molecular
      weights of RNA-binding proteins by UV crosslinking. Results of individual
      experiments are presented as examples of some techniques. Throughout the article,
      suggestions are included to avoid commonly encountered problems and to assist in
      the optimization of these techniques for the study of other RNA-binding proteins.

PMID- 10075886
TI  - Purification and RNA binding properties of the polycytidylate-binding proteins
      alphaCP1 and alphaCP2.
AB  - Regulation of mRNA turnover is a critical control mechanism of gene expression
      and is influenced by ribonucleoprotein (RNP) complexes that form on cis elements.
      All mRNAs have an intrinsic half-life and in many cases these half-lives can be
      altered by a variety of stimuli that are manifested through the formation or
      disruption of an RNP structure. The stability of alpha-globin mRNA is determined
      by elements in the 3' untranslated region that are bound by an RNP complex (alpha
      complex) which appears to control the erythroid-specific accumulation of alpha
      globin mRNA. The alpha-complex could consist of up to six distinct proteins or
      protein families. One of these families is a prominent polycytidylate binding
      activity which consists of two highly homologous proteins, alpha-complex proteins
      1 and 2 (alphaCP1 and alphaCP2). This article focuses on various methodologies
      for the detection and manipulation of alphaCP1 and alphaCP2 binding to RNA and
      details means of isolating and characterizing mRNA bound by these proteins to
      study mRNA turnover and its regulation.

PMID- 10075887
TI  - Editorial 

PMID- 10075888
TI  - Targeted linearization of DNA in vivo.
AB  - In the past decade, site-specific chromosomal DNA cleavage mediated by DNA
      endonucleases has been used to examine diverse aspects of chromosome structure
      and function in eukaryotes, such as DNA topology, replication, transcription,
      recombination, and repair. Here we describe a method with which chromosomes can
      be linearized at any predefined position in vivo. Yeast homothallic switching
      endonuclease (HO endo), a sequence-specific double-strand nuclease involved in
      mating-type switching, is employed for targeting DNA cleavage. HO endo contains
      discrete functional domains: a N-terminal nuclease and a C-terminal DNA-binding
      domain, thereby allowing construction of a chimeric nuclease with the cutting
      site distinct from the original HO recognition sequence. The expression of the
      nuclease is engineered to be controlled by a tightly regulated, inducible
      promoter. The cut sites recognized by HO endo or its derivatives are introduced
      specifically at desired positions in the yeast genome by homologous
      recombination. Here we present experimental procedures and review some
      applications based on this approach in yeast and other biological systems.

PMID- 10075889
TI  - Isolation of selected chromatin fragments from yeast by site-specific
      recombination in vivo.
AB  - A burgeoning interest in the role of chromatin structure in a wide variety of
      chromosome functions has established a need for methods to obtain chromatin in
      its native form. Here we describe a simple and efficient method for biochemical
      isolation of selected chromatin fragments from yeast chromosomes. The approach
      involves three steps. First, site-specific recombination in vivo is used to
      excise a chromosomal domain of interest in the form of a small extrachromosomal
      ring. Second, whole cell lysate is prepared from cultures in which recombination
      has been induced. Third, differential centrifugation is used to separate excised
      chromatin rings from chromosomes and other cellular debris. Using this
      methodology, we show that rings containing the transcriptionally repressed HMR
      mating-type locus can be formed and isolated in high yield. Furthermore, we show
      that the isolation procedure results in significant enrichment of recombinant
      rings. Finally, we show that the nucleosomal organization of the recombined
      material is not altered during isolation.

PMID- 10075890
TI  - Psoralen cross-linking as probe of torsional tension and topological domain size
      in vivo.
AB  - DNA within a cell is organized with unrestrained torsional tension, and each
      molecule is divided into multiple individual topological domains. Psoralen
      photobinding can be used as an assay for supercoiling and topological domain size
      in living cells. Psoralen photobinds to DNA at a rate nearly linearly
      proportional to superhelical density. Comparison of the rate of photobinding to
      supercoiled and relaxed DNA in cells provides a measure of superhelical density.
      For this, in vivo superhelical tension is relaxed by the introduction of nicks by
      either ionizing radiation or photolysis of bromodeoxyuridine in the DNA. Since
      nicks are introduced in a random fashion, the distribution of nicks is described
      by a Poisson distribution. Thus, after nicking, the fraction of topological
      domains containing no nicks is described by the zero term of the Poisson
      distribution. From measurement of the number of nicks introduced in the DNA and
      the fraction of torsional tension remaining, an average topological domain size
      can be estimated. Using this logic, procedures were designed and described for
      measuring supercoiling and domain size at specific sites in eukaryotic genomes.

PMID- 10075891
TI  - Formaldehyde cross-linking for studying nucleosomal dynamics.
AB  - Methods are described for the utilization of formaldehyde as a reversible cross
      linking agent for the characterization of protein-protein and protein-DNA
      interactions. The methods include a description of procedures to: (1) isolate and
      characterize transcriptionally active chromatin from cells cross-linked with
      formaldehyde; (2) study histone mobility during replication and transcription by
      the characterization of the formaldehyde-cross-linked histone octamer that is
      isolated from cells labeled with density-labeled amino acids; and (3) cross-link
      the in vitro reconstituted histone-DNA complex in order to maintain its
      structural state during subsequent characterization. Included in these methods
      are procedures for a second dimensional analysis of protein-protein cross-links
      in which the monomer components are electrophoretically resolved in the second
      dimension. The methods also include procedures to selectively reverse protein-DNA
      cross-links while maintaining the protein-protein cross-links. Potential
      artifacts are also discussed; i.e., data are presented which indicate that the
      helical pitch of DNA can be altered if the ionic strength is not properly
      controlled. The stability of the cross-linked nucleosome in the presence of
      altered pH or salt/urea concentrations is described in order to indicate that
      there are limitations to procedures that can be used for the subsequent
      characterization of the cross-linked complex.

PMID- 10075892
TI  - Histone proteins in vivo: cell-cycle-dependent physiological effects of exogenous
      linker histones incorporated into Physarum polycephalum.
AB  - We detail a method which allows biochemical quantities of histone proteins to be
      introduced into a living eukaryotic cell. This method involves absorption of
      purified proteins into macroplasmodia of Physarum polycephalum. Further, since
      Physarum macroplasmodia exist as syncitial culture with completely synchronous
      nuclei with respect to cell cycle events, proteins may be introduced at specific
      points during the eukaryotic cell cycle. We show that a linker histone is
      absorbed whole into these cells and are properly transported to the nuclei of the
      cell. Furthermore, we also show incorporation of linker histone H5 inhibits the
      transcriptional activities occurring during the G2 phase in Physarum. This method
      will make it possible to introduce histones modified with structural probes into
      chromatin naturally assembled in vivo.

PMID- 10075893
TI  - Modeling transcriptional regulation using microinjection into Xenopus oocytes.
AB  - Transcriptional regulation is a complex process that requires cooperation between
      specific DNA sequence elements, the DNA-binding proteins that bind to these
      sequences, the general transcriptional machinery, and chromatin. Oocyte
      microinjection offers a technique to study the integrated transcription process
      while still providing the opportunity to experimentally perturb this process. We
      describe here techniques for manipulating DNA templates and the protein
      complement of the oocyte to study multiple facets of transcriptional regulation.
      We present sample results showing that the GAL4-VP16 fusion activator is
      sensitive to distance in constructs containing only a minimal promoter, but can
      activate transcription at greater distances when proximal promoter elements are
      present.

PMID- 10075894
TI  - Chromatin assembly in yeast cell-free extracts.
AB  - A simple method for preparing chromatin assembly extracts has not been available
      for budding yeast. Here I describe such a method in detail. The assembly extract,
      a crude 100,000g supernatant, is prepared from cells disrupted in a manual or
      motorized grinder while they are frozen. The core histones and all soluble
      protein factors required for chromatin assembly under physiological conditions
      are present in the extract. Assembly is sensitive to mutation of lysine residues
      in the amino-terminal tail of histone H4 whose acetylation is associated with
      nucleosome deposition in vivo. The reaction is ATP dependent, and assembly-driven
      DNA supercoiling occurs with the same efficiency as in extracts from mammalian
      somatic cells. This simple system offers a unique opportunity to analyze
      chromatin metabolism by a combined biochemical and genetic approach that is not
      feasible for any other model organism.

PMID- 10075895
TI  - Functional analysis of chromatin assembled in synthetic nuclei.
AB  - Numerous regulatory mechanisms contribute to the control of eukaryotic
      transcription. These controls are manifested through higher-order protein-DNA
      structure within the nucleus. In vitro assays have proven extremely useful in
      deciphering the potential regulatory roles of chromatin and nuclear structure in
      transcription. Embryonic egg extracts of Xenopus with their vast maternal stores
      and rapid cell-cycle oscillations can be exploited to recapitulate multiple
      layers of nuclear regulation. Incubation of cloned DNA templates in Xenopus egg
      extracts promotes a self-ordered assembly of physiologically spaced nucleosomes
      and synthetic nuclei structure formation. Interaction of membrane vesicles with
      chromatin leads to formation of a bilayer nuclear envelope encapsulating the DNA.
      These synthetic nuclei are functional organelles capable of active protein
      transport and a single round of semiconservative DNA synthesis. This system can
      be used to directly test the mechanisms by which trans-acting factors promote
      transcription on nucleosomal DNA, either during chromatin assembly or
      postassembly or in conjunction with remodeling machinery and/or DNA replication.
      The functional consequences of trans-acting factor interaction within synthetic
      nuclei are determined by a coupled in vitro transcription analysis. Immobilizing
      biotin end-labeled DNA templates on paramagnetic streptavidin beads greatly
      improves the flexibility of the system. The ease of chromatin-assembled template
      recovery allows the introduction of wash steps, buffer changes, and specific
      reaction optimization. These methods for reconstituting gene regulatory
      mechanisms in vitro are an attempt to strike a balance between biochemical
      accessibility and physiological relevance.

PMID- 10075896
TI  - Electron spectroscopic imaging of chromatin.
AB  - The analytical electron microscope technique called electron spectroscopic
      imaging (ESI) has a number of applications in the study of DNA:protein complexes.
      The method offers an intermediate level of spatial resolution for in vitro
      structural studies of complexes that may be too large or heterogeneous to study
      by crystallography or magnetic resonance spectroscopy. An advantage of ESI is
      that the distribution of nucleic acids can be resolved in a nucleoprotein complex
      by mapping the element phosphorus, present at high levels in nucleic acid
      compared to protein. Measurements of phosphorus content together with mass
      determination allows estimates to be made of stoichiometric relationships of
      protein and nucleic acids in these complexes. ESI is also suited to in situ
      studies of nuclear structure. Mass-sensitive images combined with nitrogen and
      phosphorus maps can be used to distinguish nucleic acid components from nuclear
      structures that are predominantly protein based. Interactions between chromatin
      on the periphery of interchromatin granule clusters (IGC) with the protein
      substructure that connects the exterior of the IGC to its core can be studied
      with this technique. The method also avoids the use of heavy atom stains, agents
      required in conventional electron microscopy, that preclude the distinguishing of
      structures on the basis of their biochemical composition. The principles of ESI
      and technical aspects of the method are discussed.

PMID- 10075897
TI  - The large-scale neural network for spatial attention displays multifunctional
      overlap but differential asymmetry.
AB  - Functional magnetic resonance imaging (fMRI) was used to determine the brain
      regions activated by two types of covert visuospatial attentional shifts: one
      based on exogenous spatial priming and the other on foveally presented cues which
      endogenously regulated the direction of spatial expectancy. Activations were seen
      in the cortical and subcortical components of a previously characterized
      attentional network, namely, the frontal eye fields, posterior parietal cortex,
      the cingulate gyrus, the putamen, and the thalamus. Additional activations
      occurred in the anterior insula, dorsolateral prefrontal cortex, temporo
      occipital cortex in the middle and inferior temporal gyri, the supplementary
      motor area, and the cerebellum. Direct comparisons showed a nearly complete
      overlap in the location of activations resulting from the two tasks. However, the
      spatial priming task displayed a more pronounced rightward asymmetry of parietal
      activation, and a conjunction analysis showed that the area of posterior parietal
      cortex jointly activated by both tasks was more extensive in the right
      hemisphere. Furthermore, the posterior parietal and temporo-occipital activations
      were more pronounced in the task of endogenous attentional shifts. The results
      show that both exogenous (based on spatial priming) and endogenous (based on
      expectancy cueing) shifts of attention are subserved by a common network of
      cortical and subcortical regions. However, the differences between the two tasks,
      especially in the degree of rightward asymmetry, suggests that the pattern of
      activation within this network may show variations that reflect the specific
      attributes of the attentional task.

PMID- 10075898
TI  - Effect of familiarity on the processing of human faces.
AB  - Most brain imaging studies on face perception have investigated the processing of
      unknown faces and addressed mainly the question of specific face processing in
      the human brain. The goal of this study was to highlight the effects of
      familiarity on the visual processing of faces. Using [15O]water 3D Positron
      Emission Tomography, regional cerebral blood flow distribution was measured in 11
      human subjects performing an identical task (gender categorization) on both
      unknown and known faces. Subjects also performed two control tasks (a face
      recognition task and a visual pattern discrimination task). They were scanned
      after a training phase using videotapes during which they had been familiarized
      with and learned to recognize a set of faces. Two major results were obtained. On
      the one hand, we found bilateral activations of the fusiform gyri in the three
      face conditions, including the so-called fusiform-face area, a region in the
      right fusiform gyrus specifically devoted to face processing. This common
      activation suggests that different cognitive tasks performed on known and unknown
      faces require the involvement of this fusiform region. On the other hand,
      specific regional cerebral blood flow changes were related to the processing of
      known and unknown faces. The left amygdala, a structure involved in implicit
      learning of visual representations, was activated by the categorization task on
      unknown faces. The same task on known faces induced a relative decrease of
      activity in early visual areas. These differences between the two categorization
      tasks reveal that the human brain processes known and unknown faces differently.

PMID- 10075899
TI  - Brain activation related to the change between bimanual motor programs.
AB  - By using positron emission tomography, we aimed to identify cerebral foci of
      neuronal activation associated with the initiation of a specific motor program.
      To that end, a state of repeatedly alternating in- and antiphase of bimanual
      flexion and extension movements was compared with similar movement responses
      except phase changing. This comparison provided the opportunity to eliminate
      confounding effects of attention and simple movements. Change between the two
      bimanual motor programs was related with activation at the posterior border of
      the left angular gyrus, the right precuneus, and the right premotor and right
      medial prefrontal cortex. In a subsequent experiment, with attention and random
      movements as additional variables, activation at the posterior border of the left
      angular gyrus was found at the same significance level. This posterior parietal
      activation may indicate an equivalence with the coding of intention in monkey
      posterior parietal cortex. Lesion of the left posterior parietal cortex in human
      gives rise to left-right disorientation and ideomotor apraxia. Our results may
      support the view that these symptoms reflect the inability to transpose a motor
      plan to the representation of a personal body scheme. Activation of the right
      premotor and right medial prefrontal cortex was related both to the change
      between motor programs and to the condition with strictly regular movement in
      which no additional responses were made to randomly presented signals. This is
      consistent with the concept that motor preparation is associated with both the
      selection of internally instructed movements and the suppression of irrelevant
      environmental stimuli.

PMID- 10075900
TI  - On clustering fMRI time series.
AB  - Analysis of fMRI time series is often performed by extracting one or more
      parameters for the individual voxels. Methods based, e.g., on various statistical
      tests are then used to yield parameters corresponding to probability of
      activation or activation strength. However, these methods do not indicate whether
      sets of voxels are activated in a similar way or in different ways. Typically,
      delays between two activated signals are not identified. In this article, we use
      clustering methods to detect similarities in activation between voxels. We employ
      a novel metric that measures the similarity between the activation stimulus and
      the fMRI signal. We present two different clustering algorithms and use them to
      identify regions of similar activations in an fMRI experiment involving a visual
      stimulus.

PMID- 10075901
TI  - ROC analysis of statistical methods used in functional MRI: individual subjects.
AB  - The complicated structure of fMRI signals and associated noise sources make it
      difficult to assess the validity of various steps involved in the statistical
      analysis of brain activation. Most methods used for fMRI analysis assume that
      observations are independent and that the noise can be treated as white gaussian
      noise. These assumptions are usually not true but it is difficult to assess how
      severely these assumptions are violated and what are their practical
      consequences. In this study a direct comparison is made between the power of
      various analytical methods used to detect activations, without reference to
      estimates of statistical significance. The statistics used in fMRI are treated as
      metrics designed to detect activations and are not interpreted probabilistically.
      The receiver operator characteristic (ROC) method is used to compare the efficacy
      of various steps in calculating an activation map in the study of a single
      subject based on optimizing the ratio of the number of detected activations to
      the number of false-positive findings. The main findings are as follows:
      Preprocessing. The removal of intensity drifts and high-pass filtering applied on
      the voxel time-course level is beneficial to the efficacy of analysis. Temporal
      normalization of the global image intensity, smoothing in the temporal domain,
      and low-pass filtering do not improve power of analysis. Choices of statistics.
      the cross-correlation coefficient and t-statistic, as well as nonparametric Mann
      Whitney statistics, prove to be the most effective and are similar in
      performance, by our criterion. Task design. the proper design of task protocols
      is shown to be crucial. In an alternating block design the optimal block length
      is be approximately 18 s. Spatial clustering. an initial spatial smoothing of
      images is more efficient than cluster filtering of the statistical parametric
      activation maps.

PMID- 10075902
TI  - Functional specialization of the human auditory cortex in processing phonetic and
      musical sounds: A magnetoencephalographic (MEG) study.
AB  - Functional specialization of the human auditory cortex in processing phonetic vs
      musical sounds was investigated. While subjects watched a silent self-selected
      movie, they were presented with sequences consisting of frequent and infrequent
      phonemes (/e/ and /o/, respectively) or chords (A major and A minor,
      respectively). The subjects' brain responses to these sounds were recorded with a
      122-channel whole-head magnetometer. The data indicated that within the right
      hemisphere, the magnetoencephalographic (MEG) counterpart MMNm of the mismatch
      negativity (MMN) elicited by an infrequent chord change was stronger than the
      MMNm elicited by a phoneme change. Within the left hemisphere, the MMNm strength
      for a chord vs phoneme change did not significantly differ. Furthermore, the MMNm
      sources for the phoneme and chord changes were posterior to the P1m sources
      generated at or near the primary auditory areas. In addition, the MMNm source for
      a phoneme change was superior to that for the chord change in both hemispheres.
      The data thus provide evidence for spatially distinct cortical areas in both
      hemispheres specialized in representing phonetic and musical sounds.

PMID- 10075903
TI  - Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia.
AB  - Functional neuroimaging provides a novel means of exploring neurophysiological
      function in schizophrenia. However, most of the studies that have been carried
      out report their findings in terms of regionally localized abnormalities. In this
      paper we propose an alternative method of data analysis that emphasizes global
      integration rather than isolated regional changes in response to psychological
      tasks. In doing so, we suggest that brain abnormalities in schizophrenia are best
      characterized as a disturbance in the integration of activity across a number of
      brain regions. Using a hypothesis-led analysis, we show that the condition is
      associated with a disruption of the normal anterior cingulate modulation of
      prefronto-temporal integration. This analytical technique, we suggest, provides a
      conceptually powerful approach to the imaging of abnormal brain function in
      psychopathological conditions.

PMID- 10075904
TI  - PET studies of syntactic processing with auditory sentence presentation.
AB  - Sixteen subjects made plausibility judgments regarding auditorily presented cleft
      object and cleft subject sentences (It was the actress that the award thrilled;
      It was the award that thrilled the actress). rCBF increased in Broca's area, pars
      triangularis, when subjects processed the syntactically more complex cleft object
      sentences. The results are consistent with previous experiments using written
      materials and suggest that an increase in rCBF in Broca's area is associated with
      processing syntactically more complex sentences.

PMID- 10075905
TI  - A direct demonstration of both structure and function in the visual system:
      combining diffusion tensor imaging with functional magnetic resonance imaging.
AB  - The relationships between functional activation patterns and the structural
      properties of brain pathways have not been widely studied. The recently developed
      magnetic resonance imaging technique of diffusion tensor imaging (DTI) allows a
      full characterization of water molecule mobility in three dimensions, providing
      new structural information that is not available from other in vivo imaging
      techniques. The directional bias of diffusion (anisotropy) may be derived from
      the diffusion tensor, and is related to fiber tract integrity and orientation.
      Since DTI and functional magnetic resonance imaging (fMRI) both require rapid
      (generally echoplanar) imaging it is possible to obtain geometrically matched
      images from the two modalities. fMRI and DTI were combined in a visual system
      study using photic stimulation to demonstrate the feasibility of combining the
      two methods and to investigate the structural properties of activated regions
      compared to the white matter tracts. Blood oxygenation level-dependent (BOLD)
      fMRI activation maps were directly overlayed upon fractional anisotropy (FA)
      maps, avoiding registration and spatial transformation by carefully matching
      acquisition parameters. Activated regions had lower FA than optic radiation white
      matter, supporting the hypothesis that most BOLD signal change occurs within the
      relatively isotropic cortical grey matter. The combination of these modalities in
      future studies may provide further insights into relationships between brain
      structure and function in both health and disease.

PMID- 10075906
TI  - Colorimetric protein assay techniques.
AB  - There has been an increase in the number of colorimetric assay techniques for the
      determination of protein concentration over the past 20 years. This has resulted
      in a perceived increase in sensitivity and accuracy with the advent of new
      techniques. The present review considers these advances with emphasis on the
      potential use of such technologies in the assay of biopharmaceuticals. The
      techniques reviewed include Coomassie Blue G-250 dye binding (the Bradford
      assay), the Lowry assay, the bicinchoninic acid assay and the biuret assay. It is
      shown that each assay has advantages and disadvantages relative to sensitivity,
      ease of performance, acceptance in the literature, accuracy and
      reproducibility/coefficient of variation/laboratory-to-laboratory variation. A
      comparison of the use of several assays with the same sample population is
      presented. It is suggested that the most critical issue in the use of a
      chromogenic protein assay for the characterization of a biopharmaceutical is the
      selection of a standard for the calibration of the assay; it is crucial that the
      standard be representative of the sample. If it is not possible to match the
      standard with the sample from the perspective of protein composition, then it is
      preferable to use an assay that is not sensitive to the composition of the
      protein such as a micro-Kjeldahl technique, quantitative amino acid analysis or
      the biuret assay. In a complex mixture it might be inappropriate to focus on a
      general method of protein determination and much more informative to use specific
      methods relating to the protein(s) of particular interest, using either specific
      assays or antibody-based methods. The key point is that whatever method is
      adopted as the 'gold standard' for a given protein, this method needs to be used
      routinely for calibration.

PMID- 10075907
TI  - Real-time monitoring of recombinant antibody breakthrough during protein A
      affinity chromatography.
AB  - An on-line assay was developed to monitor antibody breakthrough in real time
      during Protein A affinity chromatography of recombinant antibodies. When loading
      cell culture fluid on to a Protein A affinity column, antibody breakthrough
      cannot be measured by UV absorbance because of the flow-through of UV-absorbing
      impurities. An assay using perfusion chromatography media with immobilized
      Protein A is a rapid, antibody-specific assay. It directly samples preparative
      column effluent, allowing real-time measurement of antibody breakthrough during
      loading of Protein A affinity chromatography. Breakthrough curves were generated
      for three column media at five flow rates, showing the effects of diffusion on
      the shape of the breakthrough curve. The breakthrough curves were used to measure
      dynamic capacity.

PMID- 10075908
TI  - The realm of microbial lipases in biotechnology.
AB  - In this review, a comprehensive and illustrious survey is made of the applied
      aspects of microbial lipases in modern biotechnological practices. Lipases are
      the most versatile biocatalyst and bring about a range of bioconversion reactions
      such as hydrolysis, interesterification, esterification, alcoholysis, acidolysis
      and aminolysis. After a brief description of the microbial sources of lipases,
      the pivotal role of lipases in the processes and products of the food and
      flavourings industry is illustrated. An illustration is presented of biomedical
      applications. The panorama of lipases in the manufacture of fine chemicals is
      depicted with special emphasis on pharmaceuticals, pesticides, cosmetics,
      biosensors and detergents. Widening applications such as those in waste
      management and improved tanning techniques are other novel aspects of lipase
      utilization that are discussed in this review.

PMID- 10075909
TI  - Comparative study of intracellular and extracellular pectinases produced by
      Penicillium frequentans.
AB  - The filamentous fungus Penicillium frequentans synthesized eleven
      polygalacturonases (PGs) and two pectinesterases (PEs) when grown in liquid
      culture supplemented with pectin. Seven PGs and the two PEs were secreted in the
      medium, whereas four PGs were not secreted. Among the secreted PGs, the endo-PG
      (band 10) and exo-PGs (band 5) were the enzymes secreted at the highest levels.
      All secreted PGs bound to lectin and their secretion and/or enzymic activities
      were inhibited by tunicamycin (TM), except for the constitutive and inducible
      endo-PG (band 10). Studies on the affinity for concanavalin A (ConA) and the
      effect of TM suggested that the secreted endo-PG and exo-PG differed in level and
      process of glycosylation. The exo-PG was characterized as a N-glycoprotein,
      whereas the endo-PG is probably an O-glycoprotein. The PGs (bands 3 and 4) were
      neither bound to ConA nor secreted and their enzymic activities were inhibited by
      TM, suggesting that they are probably N-glycoproteins with complex
      oligosaccharides of type three and tetra-antennary structure. The other PGs
      (bands 6 and 8) that were not secreted and did not bind to ConA were not
      inhibited by TM. These enzymes presented chromatographic characteristics and
      effects with TM that were similar to endo-PG (band 10), because these PGs might
      be unglycosylated or/and aggregate forms of the endo-PG (band 10).

PMID- 10075910
TI  - Use of parvovirus-like particles for vaccination and induction of multiple immune
      responses.
AB  - Expression of the VP2 gene of autonomous parvoviruses in insect cells with the
      use of the baculovirus system has led to the production of virus-like particles
      (VLPs) formed by the self-assembly of VP2. These VLPs are expressed at high
      levels and can easily be purified by salt fractionation. They are highly
      immunogenic in the corresponding host, being fully protective at doses as low as
      1-2 microg of purified material per animal. No special adjuvants are required. An
      interesting property of these particles is their usefulness as a diagnostic
      reagent for ELISA kits, which have successfully replaced conventional methods for
      parvovirus diagnostics based on haemagglutination. Another application of the
      hybrid recombinant parvovirus-like particles of pig parvovirus (PPV) and canine
      parvovirus (CPV) is its use as an antigen delivery system. PPV:VLPs containing a
      CD8(+) epitope from the lymphocytic choriomeningitis virus (LCMV) nucleoprotein
      are able to evoke a potent cytolytic T-lymphocyte response and to protect mice
      against a lethal infection with LCMV. Also, PPV:VLPs containing the C3:T epitope
      from poliovirus elicited a T helper response in mice. These T-cell epitopes were
      inserted into the N-terminus of the VP2 protein. Unfortunately, the N-terminus is
      not adequate for antibody responses because it is inside the particle. Recent
      findings have shown that fine tailoring of the point of insertion around the tip
      of loop 2 of the surface of CPV allowed the elicitation of a potent antibody
      response. Thus mice immunized with chimaeric C3:B CPV:VLPs were able to elicit a
      strong neutralizing antibody response (>3 log10 units) against poliovirus. We now
      have the possibility of using these particles to elicit different immune
      responses against single or multiple pathogens in a simple and economic way.

PMID- 10075911
TI  - Rapid screening of textile dyes employed as affinity ligands to purify enzymes
      from yeast.
AB  - A rapid method for screening potential dye ligands for use in affinity
      chromatography is described. Textile dyes were non-covalently coupled to a cross
      linked polysaccharide Sepharose(R) matrix. Yeast alcohol dehydrogenase (ADH) was
      used as the model protein for evaluating the screening system. A homogenate from
      baker's yeast was used as the crude source of enzyme. Batchwise adsorption and
      elution were used to evaluate the individual dyes. The influence of pH and ionic
      strength in the binding and elution steps was evaluated. Batch isotherms were
      used to evaluate parameter characteristics. Experimental data obtained were
      fitted to Langmuir isotherms to determine the maximum binding capacity and the
      dissociation constant for each dye evaluated in this study. A dynamic binding
      capacity of 107.6 units of ADH/g of resin was determined for Procion Turquoise
      MXG dye by frontal analysis. Specific elution with NAD+ and non-specific elution
      with 50 mM Tris/HCl buffer, pH 8.5, were tested when Procion Turquoise MXG was
      used, giving purification factors of 53.5 and 4.4 respectively. This screening
      technique is inexpensive and can be performed in a few hours. It was possible to
      predict the performance of different reactive dyes in this way, and the influence
      of pH and salt on the binding behaviour was demonstrated.

PMID- 10075912
TI  - Yeast (Saccharomyces cerevisiae) methionine aminopeptidase I: rapid purification
      and improved activity assay.
AB  - Methionine aminopeptidase (MetAP), in two isoenzymic forms, is responsible for
      hydrolysis of the initiator methionine residues from the majority of newly
      synthesized proteins. It is an essential gene product and is ubiquitously found
      in archaea, eubacteria, and lower and higher eukaryotes. MetAP also has a
      potentially important role in the production of recombinant proteins, since
      failure to correctly remove initiator methionine residues can result in a product
      that is inactive or immunogenic. A rapid two-step purification of recombinant
      yeast (Saccharomyces cerevisiae) MetAP I that produces a product that is more
      than 95% pure and maintains a high level of activity (kcat 320-1556 min-1) has
      been developed. In addition, a versatile, accurate and sensitive assay for MetAP
      activity is presented. In contrast with previous methods, which usually use short
      tripeptides and require a post-reaction derivatization step, this assay uses
      peptides ranging in size from four to eight residues and utilizes UV detection of
      a tryptophan residue at the C-terminus. As little as 1 pmol of yeast MetAP I can
      be detected, with 5 microM peptide in a 100 microl reaction. The combination of a
      rapid purification protocol and a significantly improved activity assay will
      allow for a detailed examination of MetAP structure-function relationships and
      may lead to improved enzyme reagents for use in recombinant-protein production.

PMID- 10075913
TI  - Mutational analysis of sickle haemoglobin (Hb) gelation.
AB  - The use of recombinant Hb has provided the advantage that any amino acid
      substitution can be made at sites not represented by natural mutants or that
      cannot be modified by chemical procedures. We have recently reported the
      expression of human sickle Hb (HbS) in the yeast Saccharomyces cerevisiae that
      carries a plasmid containing the human alpha- and beta-globin cDNA sequences; N
      terminal nascent protein processing is correct and a soluble correctly folded Hb
      tetramer is produced. The yeast system produces a recombinant sickle Hb that is
      identical by about a dozen biochemical and physiological criteria with the
      natural sickle Hb purified from the red cells of sickle-cell anaemia patients.
      Most importantly, the gelling concentration of this recombinant sickle Hb is the
      same as that of the HbS purified from human sickle red cells. The misfolding of
      Hb reported for the Escherichia coli-expressed protein is not apparent for Hb
      expressed in yeast by any of the criteria that we have used for characterization.
      These findings indicate that this system is well suited to the production of HbS
      mutants to explore those areas of the HbS tetramer whose roles in the gelation
      process are not yet defined and to measure quantitatively the strength of such
      interactions at certain inter-tetrameric contact sites in the deoxy-HbS
      aggregate. This article reviews our studies on a number of sickle Hb mutants,
      including polymerization-enhancing HbS mutants and polymerization-inhibiting HbS
      mutants.

PMID- 10075914
TI  - Immobilization of horseradish peroxidase in cross-linked phyllosilicates:
      conditions and characterizations.
AB  - An innovative immobilization procedure was developed for intercalation of enzymes
      into dispersed phyllosilicates which were cross-linked with silicates resulting
      from the hydrolysis of tetramethyl orthosilicate. Donor:hydrogen-peroxide
      oxidoreductase intercalative immobilized in the cross-linked phyllosilicate
      exhibited a similar or higher activity than the free enzyme. The kinetic
      properties of peroxidase were unaffected by intercalative immobilization.
      Different factors, including drying methods, particle size, surface cations of
      the phyllosilicate and ratio of phyllosilicate to tetramethyl orthosilicate, were
      investigated to optimize immobilization conditions. The immobilized peroxidase
      exhibited similar kinetic properties to the free enzyme and good storage
      stability.

PMID- 10075915
TI  - How translational accuracy influences reading frame maintenance.
AB  - Most missense errors have little effect on protein function, since they only
      exchange one amino acid for another. However, processivity errors, frameshifting
      or premature termination result in a synthesis of an incomplete peptide. There
      may be a connection between missense and processivity errors, since processivity
      errors now appear to result from a second error occurring after recruitment of an
      errant aminoacyl-tRNA, either spontaneous dissociation causing premature
      termination or translational frameshifting. This is clearest in programmed
      translational frameshifting where the mRNA programs errant reading by a near
      cognate tRNA; this error promotes a second frameshifting error (a dual-error
      model of frameshifting). The same mechanism can explain frameshifting by
      suppressor tRNAs, even those with expanded anticodon loops. The previous model
      that suppressor tRNAs induce quadruplet translocation now appears incorrect for
      most, and perhaps for all of them. We suggest that the 'spontaneous' tRNA-induced
      frameshifting and 'programmed' mRNA-induced frameshifting use the same mechanism,
      although the frequency of frameshifting is very different. This new model of
      frameshifting suggests that the tRNA is not acting as the yardstick to measure
      out the length of the translocation step. Rather, the translocation of 3
      nucleotides may be an inherent feature of the ribosome.

PMID- 10075916
TI  - The high-resolution crystal structure of the molybdate-dependent transcriptional
      regulator (ModE) from Escherichia coli: a novel combination of domain folds.
AB  - The molybdate-dependent transcriptional regulator (ModE) from Escherichia coli
      functions as a sensor of molybdate concentration and a regulator for
      transcription of operons involved in the uptake and utilization of the essential
      element, molybdenum. We have determined the structure of ModE using multi
      wavelength anomalous dispersion. Selenomethionyl and native ModE models are
      refined to 1. 75 and 2.1 A, respectively and describe the architecture and
      structural detail of a complete transcriptional regulator. ModE is a homodimer
      and each subunit comprises N- and C-terminal domains. The N-terminal domain
      carries a winged helix-turn-helix motif for binding to DNA and is primarily
      responsible for ModE dimerization. The C-terminal domain contains the molybdate
      binding site and residues implicated in binding the oxyanion are identified. This
      domain is divided into sub-domains a and b which have similar folds, although the
      organization of secondary structure elements varies. The sub-domain fold is
      related to the oligomer binding-fold and similar to that of the subunits of
      several toxins which are involved in extensive protein-protein interactions. This
      suggests a role for the C-terminal domain in the formation of the ModE-protein
      DNA complexes necessary to regulate transcription. Modelling of ModE interacting
      with DNA suggests that a large distortion of DNA is not necessary for complex
      formation.

PMID- 10075917
TI  - X-ray structure of T4 endonuclease VII: a DNA junction resolvase with a novel
      fold and unusual domain-swapped dimer architecture.
AB  - Phage T4 endonuclease VII (Endo VII), the first enzyme shown to resolve Holliday
      junctions, recognizes a broad spectrum of DNA substrates ranging from branched
      DNAs to single base mismatches. We have determined the crystal structures of the
      Ca2+-bound wild-type and the inactive N62D mutant enzymes at 2.4 and 2.1 A,
      respectively. The Endo VII monomers form an elongated, highly intertwined
      molecular dimer exhibiting extreme domain swapping. The major dimerization
      elements are two pairs of antiparallel helices forming a novel 'four-helix cross'
      motif. The unique monomer fold, almost completely lacking beta-sheet structure
      and containing a zinc ion tetrahedrally coordinated to four cysteines, does not
      resemble any of the known junction-resolving enzymes, including the Escherichia
      coli RuvC and lambda integrase-type recombinases. The S-shaped dimer has two
      'binding bays' separated by approximately 25 A which are lined by positively
      charged residues and contain near their base residues known to be essential for
      activity. These include Asp40 and Asn62, which function as ligands for the bound
      calcium ions. A pronounced bipolar charge distribution suggests that branched DNA
      substrates bind to the positively charged face with the scissile phosphates
      located near the divalent cations. A model for the complex with a four-way DNA
      junction is presented.

PMID- 10075918
TI  - The three-dimensional structure of the RNA-binding domain of ribosomal protein
      L2; a protein at the peptidyl transferase center of the ribosome.
AB  - Ribosomal protein L2 is the largest protein component in the ribosome. It is
      located at or near the peptidyl transferase center and has been a prime candidate
      for the peptidyl transferase activity. It binds directly to 23S rRNA and plays a
      crucial role in its assembly. The three-dimensional structure of the RNA-binding
      domain of L2 from Bacillus stearothermophilus has been determined at 2.3 A
      resolution by X-ray crystallography using the selenomethionyl MAD method. The RNA
      binding domain of L2 consists of two recurring motifs of approximately 70
      residues each. The N-terminal domain (positions 60-130) is homologous to the OB
      fold, and the C-terminal domain (positions 131-201) is homologous to the SH3-like
      barrel. Residues Arg86 and Arg155, which have been identified by mutation
      experiments to be involved in the 23S rRNA binding, are located at the gate of
      the interface region between the two domains. The molecular architecture suggests
      how this important protein has evolved from the ancient nucleic acid-binding
      proteins to create a 23S rRNA-binding domain in the very remote past.

PMID- 10075919
TI  - Crystal structure of a heparin- and integrin-binding segment of human
      fibronectin.
AB  - The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals
      the primary heparin-binding site, a clump of positively charged residues in FN13,
      and a putative minor site approximately 60 A away in FN14. The IDAPS motif
      implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering
      the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14,
      whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9.
      Mutagenesis studies prompted by this observation reveal that both arginines of
      the PRARI sequence are important for alpha4beta1 binding to FN12-14. The PRARI
      motif may represent a new class of integrin-binding sites. The spatial
      organization of the binding sites suggests that heparin and integrin may bind in
      concert.

PMID- 10075920
TI  - EFA6, a sec7 domain-containing exchange factor for ARF6, coordinates membrane
      recycling and actin cytoskeleton organization.
AB  - We have identified a human cDNA encoding a novel protein, exchange factor for
      ARF6 (EFA6), which contains Sec7 and pleckstrin homology domains. EFA6 promotes
      efficient guanine nucleotide exchange on ARF6 and is distinct from the ARNO
      family of ARF1 exchange factors. The protein localizes to a dense matrix on the
      cytoplasmic face of plasma membrane invaginations, induced on its expression. We
      show that EFA6 regulates endosomal membrane recycling and promotes the
      redistribution of transferrin receptors to the cell surface. Furthermore,
      expression of EFA6 induces actin-based membrane ruffles that are inhibited by co
      expression of dominant-inhibitory mutant forms of ARF6 or Rac1. Our results
      demonstrate that by catalyzing nucleotide exchange on ARF6 at the plasma membrane
      and by regulating Rac1 activation, EFA6 coordinates endocytosis with cytoskeletal
      rearrangements.

PMID- 10075921
TI  - The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion
      channel constructed from two membrane-spanning domains (MSDs), two nucleotide
      binding domains (NBD) and a regulatory (R) domain. The NBDs and R-domain are
      cytosolic and how they are assembled with the MSDs to achieve the native CFTR
      structure is not clear. Human DnaJ 2 (Hdj-2) is a co-chaperone of heat shock
      cognate 70 (Hsc70) which is localized to the cytosolic face of the ER. Whether
      Hdj-2 directs Hsc70 to facilitate the assembly of cytosolic regions on CFTR was
      investigated. We report that immature ER forms of CFTR and DeltaF508 CFTR can be
      isolated in complexes with Hdj-2 and Hsc70. The DeltaF508 mutation is localized
      in NBD1 and causes the CFTR to misfold. Levels of complex formation between
      DeltaF508 CFTR and Hdj-2/Hsp70 were approximately 2-fold higher than those with
      CFTR. The earliest stage at which Hdj-2/Hsc70 could bind CFTR translation
      intermediates coincided with the expression of NBD1 in the cytosol.
      Interestingly, complex formation between Hdj-2 and nascent CFTR was greatly
      reduced after expression of the R-domain. In experiments with purified
      components, Hdj-2 and Hsc70 acted synergistically to suppress NBD1 aggregation.
      Collectively, these data suggest that Hdj-2 and Hsc70 facilitate early steps in
      CFTR assembly. A putative step in the CFTR folding pathway catalyzed by Hdj
      2/Hsc70 is the formation of an intramolecular NBD1-R-domain complex. Whether this
      step is defective in the biogenesis of DeltaF508 CFTR will be discussed.

PMID- 10075922
TI  - Sac1p plays a crucial role in microsomal ATP transport, which is distinct from
      its function in Golgi phospholipid metabolism.
AB  - Analysis of microsomal ATP transport in yeast resulted in the identification of
      Sac1p as an important factor in efficient ATP uptake into the endoplasmic
      reticulum (ER) lumen. Yet it remained unclear whether Sac1p is the authentic
      transporter in this reaction. Sac1p shows no homology to other known solute
      transporters but displays similarity to the N-terminal non-catalytic domain of a
      subset of inositol 5'-phosphatases. Furthermore, Sac1p was demonstrated to be
      involved in inositol phospholipid metabolism, an activity whose absence
      contributes to the bypass Sec14p phenotype in sac1 mutants. We now show that
      purified recombinant Sac1p can complement ATP transport defects when
      reconstituted together with sac1Delta microsomal extracts, but is unable to
      catalyze ATP transport itself. In addition, we demonstrate that sac1Delta strains
      are defective in ER protein translocation and folding, which is a direct
      consequence of impaired ATP transport function and not related to the role of
      Sac1p in Golgi inositol phospholipid metabolism. These data suggest that Sac1p is
      an important regulator of microsomal ATP transport providing a possible link
      between inositol phospholipid signaling and ATP-dependent processes in the yeast
      ER.

PMID- 10075923
TI  - Dual roles of sialyl Lewis X oligosaccharides in tumor metastasis and rejection
      by natural killer cells.
AB  - Aberrant expression of cell surface carbohydrates such as sialyl Lewis X is
      associated with tumor formation and metastasis. In order to determine the roles
      of sialyl Lewis X in tumor metastasis, mouse melanoma B16-F1 cells were stably
      transfected with alpha1, 3-fucosyltransferase III to express sialyl Lewis X
      structures. The transfected B16-F1 cells, B16-FTIII, were separated by cell
      sorting into three different groups based on the expression levels of sialyl
      Lewis X. When these transfected cells were injected into tail veins of C57BL/6
      mice, B16-FTIII.M cells expressing moderate amounts of sialyl Lewis X in poly-N
      acetyllactosamines produced large numbers of lung tumor nodules. Surprisingly,
      B16-FTIII.H cells expressing the highest amount of sialyl Lewis X in shorter N
      glycans died in lung blood vessels, producing as few lung nodules as B16-FTIII.N
      cells which lack sialyl Lewis X. In contrast, B16-FIII.H cells formed more tumors
      in beige mice and NK cell-depleted C57BL/6 mice than did B16-FTIII.M cells. B16
      FTIII.H cells bound to E-selectin better than did B16-FTIII.M cells, but both
      cells grew at the same rate. These results indicate that excessive expression of
      sialyl Lewis X in tumor cells leads to rejection by NK cells rather than tumor
      formation facilitated by attachment to endothelial cells.

PMID- 10075924
TI  - Specific destruction of kinetochore protein CENP-C and disruption of cell
      division by herpes simplex virus immediate-early protein Vmw110.
AB  - Examination of cells at the early stages of herpes simplex virus type 1 infection
      revealed that the viral immediate-early protein Vmw110 (also known as ICP0)
      formed discrete punctate accumulations associated with centromeres in both
      mitotic and interphase cells. The RING finger domain of Vmw110 (but not the C
      terminal region) was essential for its localization at centromeres, thus
      distinguishing the Vmw110 sequences required for centromere association from
      those required for its localization at other discrete nuclear structures known as
      ND10, promyelocytic leukaemia (PML) bodies or PODs. We have shown recently that
      Vmw110 can induce the proteasome-dependent loss of several cellular proteins,
      including a number of probable SUMO-1-conjugated isoforms of PML, and this
      results in the disruption of ND10. In this study, we found some striking
      similarities between the interactions of Vmw110 with ND10 and centromeres.
      Specifically, centromeric protein CENP-C was lost from centromeres during virus
      infection in a Vmw110- and proteasome-dependent manner, causing substantial
      ultrastructural changes in the kinetochore. In consequence, dividing cells either
      became stalled in mitosis or underwent an unusual cytokinesis resulting in
      daughter cells with many micronuclei. These results emphasize the importance of
      CENP-C for mitotic progression and suggest that Vmw110 may be interfering with
      biochemical mechanisms which are relevant to both centromeres and ND10.

PMID- 10075925
TI  - Identification of heparin-binding EGF-like growth factor as a target in
      intercellular regulation of epidermal basal cell growth by suprabasal retinoic
      acid receptors.
AB  - The role of retinoic acid receptors (RARs) in intercellular regulation of cell
      growth was assessed by targeting a dominant-negative RARalpha mutant (dnRARalpha)
      to differentiated suprabasal cells of mouse epidermis. dnRARalpha lacks
      transcriptional activation but not DNA-binding and receptor dimerization
      functions. Analysis of transgenic mice revealed that dnRARalpha dose-dependently
      impaired induction of basal cell proliferation and epidermal hyperplasia by all
      trans RA (tRA). dnRARalpha formed heterodimers with endogenous retinoid X
      receptor-alpha (RXRalpha) over RA response elements in competition with remaining
      endogenous RARgamma-RXRalpha heterodimers, and dose-dependently impaired retinoid
      dependent gene transcription. To identify genes regulated by retinoid receptors
      and involved in cell growth control, we analyzed the retinoid effects on
      expression of the epidermal growth factor (EGF) receptor, EGF, transforming
      growth factor-alpha, heparin-binding EGF-like growth factor (HB-EGF) and
      amphiregulin genes. In normal epidermis, tRA rapidly and selectively induced
      expression of HB-EGF but not the others. This induction occurred exclusively in
      suprabasal cells. In transgenic epidermis, dnRARalpha dose-dependently inhibited
      tRA induction of suprabasal HB-EGF and subsequent basal cell hyperproliferation.
      Together, our observations suggest that retinoid receptor heterodimers located in
      differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in
      turn stimulates basal cell growth via intercellular signaling. These events may
      underlie retinoid action in epidermal regeneration during wound healing.

PMID- 10075926
TI  - Autosomal SCID caused by a point mutation in the N-terminus of Jak3: mapping of
      the Jak3-receptor interaction domain.
AB  - Signaling through the hematopoietic receptors requires activation of receptor
      associated Janus (Jak) kinases. For example, Jak1 and Jak3 bind specifically to
      the IL-2 receptor beta (IL-2Rbeta) and common gamma (gammac) chains,
      respectively, and initiate biochemical signals critical in controlling immune
      responses. The region of Jak responsible for receptor interactions, however, is
      not well characterized. Here we describe a naturally occurring Jak3 mutation from
      a patient with autosomal severe combined immunodeficiency (SCID), where a single
      amino acid substitution, Y100C, in Janus homology domain 7 (JH7) prevents kinase
      receptor interaction. This mutation also results in a loss of IL-2-induced
      signaling in a B-cell line derived from this patient. Using mutational analysis
      we have identified a region of Jak3, including portions of JH6 and JH7, that is
      sufficient for kinase-receptor contact and show that this segment interacts with
      the proline-rich Box1 region of the receptor. Furthermore, a Jak3-Jak1 chimera
      containing only the JH6 and JH7 domains of Jak3 interacts with gammac and can
      reconstitute IL-2-dependent responses, including receptor phosphorylation and
      activation of signal transducer and activator of transcription (STAT) 5b. Our
      results suggest that the N-terminus of Jak kinases is critical for receptor
      binding, and is therefore likely to determine specificity of Jak kinase-receptor
      interactions.

PMID- 10075927
TI  - Regulation of Rb and E2F by signal transduction cascades: divergent effects of
      JNK1 and p38 kinases.
AB  - The E2F transcription factor plays a major role in cell cycle regulation,
      differentiation and apoptosis, but it is not clear how it is regulated by non
      mitogenic signaling cascades. Here we report that two kinases involved in signal
      transduction have opposite effects on E2F function: the stress-induced kinase
      JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated
      repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of
      JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha
      had a similar effect. Fas stimulation of Jurkat cells is known to induce p38
      kinase and we find a pronounced increase in Rb phosphorylation within 30 min of
      Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and
      increased transcriptional activity. The inactivation of Rb by Fas was blocked by
      SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct;
      cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no
      effect. These results suggest that Fas-mediated inactivation of Rb is mediated
      via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle
      regulatory pathway appears to be a normal target for non-mitogenic signaling
      cascades and could be involved in mediating the cellular effects of such signals.

PMID- 10075928
TI  - The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D
      dependent kinases in murine fibroblasts.
AB  - The widely prevailing view that the cyclin-dependent kinase inhibitors (CKIs) are
      solely negative regulators of cyclin-dependent kinases (CDKs) is challenged here
      by observations that normal up-regulation of cyclin D- CDK4 in mitogen-stimulated
      fibroblasts depends redundantly upon p21(Cip1) and p27(Kip1). Primary mouse
      embryonic fibroblasts that lack genes encoding both p21 and p27 fail to assemble
      detectable amounts of cyclin D-CDK complexes, express cyclin D proteins at much
      reduced levels, and are unable to efficiently direct cyclin D proteins to the
      cell nucleus. Restoration of CKI function reverses all three defects and thereby
      restores cyclin D activity to normal physiological levels. In the absence of both
      CKIs, the severe reduction in cyclin D-dependent kinase activity was well
      tolerated and had no overt effects on the cell cycle.

PMID- 10075929
TI  - The GATA factor AreA is essential for chromatin remodelling in a eukaryotic
      bidirectional promoter.
AB  - The linked niiA and niaD genes of Aspergillus nidulans are transcribed
      divergently. The expression of these genes is subject to a dual control system.
      They are induced by nitrate and repressed by ammonium. AreA mediates derepression
      in the absence of ammonium and NirA supposedly mediates nitrate induction. Out of
      10 GATA sites, a central cluster (sites 5-8) is responsible for approximately 80%
      of the transcriptional activity of the promoter on both genes. We show occupancy
      in vivo of site 5 by the AreA protein, even under conditions of repression. Sites
      5-8 are situated in a pre-set nucleosome-free region. Under conditions of
      expression, a drastic nucleosomal rearrangement takes place and the positioning
      of at least five nucleosomes flanking the central region is lost. Remodelling is
      strictly dependent on the presence of an active areA gene product, and
      independent from the NirA-specific and essential transcription factor. Thus,
      nucleosome remodelling is independent from the transcriptional activation of the
      niiA-niaD promoter. The results presented cast doubts on the role of NirA as the
      unique transducer of the nitrate induction signal. We demonstrate, for the first
      time in vivo, that a GATA factor is involved directly in chromatin remodelling.

PMID- 10075930
TI  - A comparison of in vivo and in vitro DNA-binding specificities suggests a new
      model for homeoprotein DNA binding in Drosophila embryos.
AB  - Little is known about the range of DNA sequences bound by transcription factors
      in vivo. Using a sensitive UV cross-linking technique, we show that three classes
      of homeoprotein bind at significant levels to the majority of genes in Drosophila
      embryos. The three classes bind with specificities different from each other;
      however, their levels of binding on any single DNA fragment differ by no more
      than 5- to 10-fold. On actively transcribed genes, there is a good correlation
      between the in vivo DNA-binding specificity of each class and its in vitro DNA
      binding specificity. In contrast, no such correlation is seen on inactive or
      weakly transcribed genes. These genes are bound poorly in vivo, even though they
      contain many high affinity homeoprotein-binding sites. Based on these results, we
      suggest how the in vivo pattern of homeoprotein DNA binding is determined.

PMID- 10075931
TI  - Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their
      autoinhibitory domains.
AB  - The transcription factors Ets-1 and AML1 (the alphaBl subunit of PEBP2/CBF) play
      critical roles in hematopoiesis and leukemogenesis, and cooperate in the
      transactivation of the T cell receptor (TCR) beta chain enhancer. The DNA binding
      capacity of both factors is blocked intramolecularly but can be activated by the
      removal of negative regulatory domains. These include the exon VII domain for Ets
      1 and the negative regulatory domain for DNA binding (NRDB) for alphaB1. Here we
      report that the direct interaction between the two factors leads to a reciprocal
      stimulation of their DNA binding activity and activation of their transactivation
      function. Detailed mapping revealed two independent contact points involving the
      exon VII and NRDB regions as well as the two DNA binding domains. Using deletion
      variants and dominant interfering mutants, we demonstrate that the interaction
      between exon VII and NRDB is necessary and sufficient for cooperative DNA
      binding. The exon VII and NRDB motifs are highly conserved in evolution yet
      deleted in natural variants, suggesting that the mechanism described is of
      biological relevance. The mutual activation of DNA binding of Ets and AML1
      through the intermolecular interaction of autoinhibitory domains may represent a
      novel principle for the regulation of transcription factor function.

PMID- 10075932
TI  - A trans-acting peptide activates the yeast a1 repressor by raising its DNA
      binding affinity.
AB  - The cooperative binding of gene regulatory proteins to DNA is a common feature of
      transcriptional control in both prokaryotes and eukaryotes. It is generally
      viewed as a simple energy coupling, through protein-protein interactions, of two
      or more DNA-binding proteins. In this paper, we show that the simple view does
      not account for the cooperative DNA binding of a1 and alpha2, two homeodomain
      proteins from budding yeast. Rather, we show through the use of chimeric proteins
      and synthetic peptides that, upon heterodimerization, alpha2 instructs a1 to bind
      DNA. This change is induced by contact with a peptide contributed by alpha2, and
      this contact converts a1 from a weak to a strong DNA-binding protein. This
      explains, in part, how high DNA-binding specificity is achieved only when the two
      gene regulatory proteins conjoin. We also provide evidence that features of the
      a1-alpha2 interaction can serve as a model for other examples of protein-protein
      interactions, including that between the herpes virus transcriptional activator
      VP16 and the mammalian homeodomain-containing protein Oct-l.

PMID- 10075933
TI  - A function of CBP as a transcriptional co-activator during Dpp signalling.
AB  - CBP/p300 is a transcriptional co-activator that is recruited to enhancers by
      various DNA-binding proteins, including proteins whose activity is controlled by
      extracellular signals. Here, we report that Drosophila CBP loss-of-function
      mutants show specific defects which mimic those seen in mutants that lack the
      extracellular signal Dpp or its effector Mad. Furthermore, we find that CBP loss
      severely compromises the ability of Dpp target enhancers to respond to endogenous
      or exogenous Dpp. Finally, we show that CBP binds to the C-terminal domain of
      Mad. Our results provide evidence that CBP functions as a co-activator during Dpp
      signalling, and they suggest that Mad may recruit CBP to effect the
      transcriptional activation of Dpp-responsive genes during development.

PMID- 10075934
TI  - Intronless mRNA transport elements may affect multiple steps of pre-mRNA
      processing.
AB  - We have reported recently that a small element within the mouse histone H2a
      coding region permits efficient cytoplasmic accumulation of intronless beta
      globin cDNA transcripts. This sequence lowers the levels of spliced products from
      intron-containing constructs and can functionally replace Rev and the Rev
      responsive element (RRE) in the nuclear export of unspliced HIV-1-related mRNAs.
      In work reported here, we further investigate the molecular mechanisms by which
      this element might work. We demonstrate here through both in vivo and in vitro
      assays that, in addition to promoting mRNA nuclear export, this element acts as a
      polyadenylation enhancer and as a potent inhibitor of splicing. Surprisingly, two
      other described intronless mRNA transport elements (from the herpes simplex virus
      thymidine kinase gene and hepatitis B virus) appear to function in a similar
      manner. These findings prompt us to suggest that a general feature of intronless
      mRNA transport elements might be a collection of phenotypes, including the
      inhibition of splicing and the enhancement of both polyadenylation and mRNA
      export.

PMID- 10075935
TI  - Massive presence of the Escherichia coli 'major cold-shock protein' CspA under
      non-stress conditions.
AB  - The most characteristic event of cold-shock activation in Escherichia coli is
      believed to be the de novo synthesis of CspA. We demonstrate, however, that the
      cellular concentration of this protein is > or = 50 microM during early
      exponential growth at 37 degrees C; therefore, its designation as a major cold
      shock protein is a misnomer. The cspA mRNA level decreases rapidly with
      increasing cell density, becoming virtually undetectable by mid-to-late
      exponential growth phase while the CspA level declines, although always remaining
      clearly detectable. A burst of cspA expression followed by a renewed decline
      ensues upon dilution of stationary phase cultures with fresh medium. The extent
      of cold-shock induction of cspA varies as a function of the growth phase, being
      inversely proportional to the pre-existing level of CspA which suggests feedback
      autorepression by this protein. Both transcriptional and post-transcriptional
      controls regulate cspA expression under non-stress conditions; transcription of
      cspA mRNA is under the antagonistic control of DNA-binding proteins Fis and H-NS
      both in vivo and in vitro, while its decreased half-life with increasing cell
      density contributes to its rapid disappearance. The cspA mRNA instability is due
      to its 5' untranslated leader and is counteracted in vivo by the cold-shock DeaD
      box RNA helicase (CsdA).

PMID- 10075936
TI  - A leucine-rich nuclear export signal in the p53 tetramerization domain:
      regulation of subcellular localization and p53 activity by NES masking.
AB  - Appropriate subcellular localization is crucial for regulating p53 function. We
      show that p53 export is mediated by a highly conserved leucine-rich nuclear
      export signal (NES) located in its tetramerization domain. Mutation of NES
      residues prevented p53 export and hampered tetramer formation. Although the p53
      binding protein MDM2 has an NES and has been proposed to mediate p53 export, we
      show that the intrinsic p53 NES is both necessary and sufficient for export. This
      report also demonstrates that the cytoplasmic localization of p53 in
      neuroblastoma cells is due to its hyperactive nuclear export: p53 in these cells
      can be trapped in the nucleus by the export-inhibiting drug leptomycin B or by
      binding a p53-tetramerization domain peptide that masks the NES. We propose a
      model in which regulated p53 tetramerization occludes its NES, thereby ensuring
      nuclear retention of the DNA-binding form. We suggest that attenuation of p53
      function involves the conversion of tetramers into monomers or dimers, in which
      the NES is exposed to the proteins which mediate their export to the cytoplasm.

PMID- 10075937
TI  - Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and
      GDP-GTP exchange factors in translation initiation, mediate binding to their
      common substrate eIF2.
AB  - In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis
      of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the
      resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange
      factor, eIF2B. Bipartite motifs rich in aromatic and acidic residues are
      conserved at the C-termini of eIF5 and the catalytic (epsilon) subunit of eIF2B.
      Here we show that these bipartite motifs are important for the binding of these
      factors, both in vitro and in vivo, to the beta subunit of their common substrate
      eIF2. We also find that three lysine-rich boxes in the N-terminal segment of
      eIF2beta mediate the binding of eIF2 to both eIF5 and eIF2B. Thus, eIF5 and
      eIF2Bepsilon employ the same sequence motif to facilitate interaction with the
      same segment of their common substrate. In agreement with this, archaea appear to
      lack eIF5, eIF2B and the lysine-rich binding domain for these factors in their
      eIF2beta homolog. The eIF5 bipartite motif is also important for its interaction
      with the eIF3 complex through the NIP1-encoded subunit of eIF3. Thus, the
      bipartite motif in eIF5 appears to be multifunctional, stimulating its
      recruitment to the 40S pre-initiation complex through interaction with eIF3 in
      addition to binding of its substrate eIF2.

PMID- 10075938
TI  - Self assembly of NuMA: multiarm oligomers as structural units of a nuclear
      lattice.
AB  - NuMA is a nuclear matrix protein in interphase and relocates to the spindle poles
      in mitotis. Different NuMA constructs, in which either N- or C-terminal domains
      were deleted, and the full-length construct were expressed in Escherichia coli,
      and the NuMA polypeptides were purified to homogeneity and allowed to assemble in
      vitro. Electron microscopy showed that NuMA can build multiarm oligomers by
      interaction of the C-terminal globular domains. Each arm of the oligomer
      corresponds to a NuMA dimer. Oligomers with up to 10 or 12 arms have been
      observed for both full-length NuMA and for constructs that still contain the
      proximal part of the C-terminal tail domain. Other results from this laboratory
      have shown that transient overexpression of NuMA in HeLa cells induces a nuclear
      scaffold with a quasi-hexagonal organization that can fill the nuclei. Here we
      show that computer modelling of the three-dimensional packing of NuMA into such
      scaffolds can explain the different spacing of the hexagons seen when constructs
      with different coiled-coil lengths are used. Thus, the 12 arm oligomer, for which
      we have in vitro evidence, may be the structural unit from which the nuclear
      scaffold in transfected cells is built.

PMID- 10075939
TI  - The essential role of yeast topoisomerase III in meiosis depends on
      recombination.
AB  - Yeast cells mutant for TOP3, the gene encoding the evolutionary conserved type I
      5' topoisomerase, display a wide range of phenotypes including altered cell
      cycle, hyper-recombination, abnormal gene expression, poor mating, chromosome
      instability and absence of sporulation. In this report, an analysis of the role
      of TOP3 in the meiotic process indicates that top3Delta mutants enter meiosis and
      complete the initial steps of recombination. However, reductional division does
      not occur. Deletion of the SPO11 gene, which prevents recombination between
      homologous chromosomes in meiosis I division, allows top3Delta mutants to form
      viable spores, indicating that Top3 is required to complete recombination
      successfully. A topoisomerase activity is involved in this process, since
      expression of bacterial TopA in yeast top3Delta mutants permits sporulation. The
      meiotic block is also partially suppressed by a deletion of SGS1, a gene encoding
      a helicase that interacts with Top3. We propose an essential role for Top3 in the
      processing of molecules generated during meiotic recombination.

PMID- 10075940
TI  - Distribution of minichromosomes in individual Escherichia coli cells:
      implications for replication control.
AB  - A novel method was devised to measure the number of plasmids in individual
      Escherichia coli cells. With this method, involving measurement of plasmid-driven
      expression of the green fluorescent protein gene by flow cytometry, the copy
      number distribution of a number of different plasmids was measured. Whereas
      natural plasmids had fairly narrow distributions, minichromosomes, which are
      plasmids replicating only from a cloned oriC copy, have a wide distribution,
      suggesting that there is no copy number control for minichromosomes. When the
      selection pressure (kanamycin concentration) for minichromosomes was increased,
      the copy number of minichromosomes was also increased. At up to 30
      minichromosomes per host chromosome, replication and growth of the host cell was
      unaffected. This is evidence that there is no negative element for initiation
      control in oriC and that there is no incompatibility between oriC located on the
      chromosome and minichromosome. However, higher copy numbers led to integration of
      the minichromosomes at the chromosomal oriC and to initiation asynchrony of the
      host chromosome. At a minichromosome copy number of approximately 30, the cell's
      capacity for synchronous initiation is exceeded and free minichromosomes will
      compete out the chromosome to yield inviable cells, unless the minichromosomes
      are incorporated into the chromosome.

PMID- 10075941
TI  - What keeps hepatocytes on the straight and narrow? Maintaining differentiated
      function in the liver.

PMID- 10075942
TI  - Helicobacter pylori resists arrest.

PMID- 10075943
TI  - Omeprazole: Helicobacter pylori makes thee greater yet.

PMID- 10075944
TI  - The hiatus hernia slides back into prominence.

PMID- 10075945
TI  - The quality of quality of life.

PMID- 10075946
TI  - New kids on the block: pancreatic stellate cells enter the fibrogenesis world.

PMID- 10075947
TI  - Budd-Chiari syndrome: blocked veins, open mind.

PMID- 10075948
TI  - Proteolytic release of membrane bound intercellular regulators.

PMID- 10075949
TI  - Balsalazide led to greater remission rates and tolerance than mesalamine in acute
      ulcerative colitis.

PMID- 10075950
TI  - Role of apoptosis induced by Helicobacter pylori infection in the development of
      duodenal ulcer.
AB  - BACKGROUND: Helicobacter pylori affects gastric epithelium integrity by
      acceleration of apoptosis. However, it remains unclear what product of the
      bacteria causes apoptosis, or whether or not the apoptosis is involved in the
      development of ulcers. AIMS: To elucidate the factor from H pylori that causes
      acceleration of apoptosis and the role of apoptosis in the development of
      duodenal ulcer in H pylori infection. PATIENTS: Five H pylori negative healthy
      volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori
      positive patients with gastric ulcer. METHODS: An endoscopic examination was
      carried out to diagnose ulcers and determine their clinical stage. To analyse
      apoptosis, a cell cycle analysis was performed using biopsy specimens. RESULTS:
      There was a significant correlation between the urease activity of the H pylori
      strain and the level of apoptosis induced by this bacterial strain. Moreover, in
      duodenal ulcer patients infected with H pylori, the patients with an active ulcer
      exhibited a significantly higher level of apoptosis than those with ulcers at
      both the healing and scarring stages. CONCLUSION: These findings suggest that
      acceleration of apoptosis in the antral mucosa caused by the urease of H pylori
      plays a crucial role in the development of ulcers in the duodenum.

PMID- 10075951
TI  - Direct detection of Helicobacter pylori resistance to macrolides by a polymerase
      chain reaction/DNA enzyme immunoassay in gastric biopsy specimens.
AB  - BACKGROUND: The increasing use of macrolides especially in the treatment of
      Helicobacter pylori infection has led to an increase in resistant strains. The
      resistance of H pylori to macrolides, especially clarithromycin, is one of the
      major causes of eradication failure. In H pylori, clarithromycin resistance is
      due to point mutations localised in domain V of 23S rRNA. AIM: To develop a
      molecular technique based on amplification of a relevant fragment of the 23S rRNA
      and colorimetric hybridisation in liquid phase to detect directly in biopsy
      specimens the type of mutation associated with resistance of H pylori to
      clarithromycin. METHODS: Gastric biopsy samples from 61 patients were submitted
      to this test. The results were compared with standard methods (determination of
      minimal inhibition concentration, polymerase chain reaction/restriction fragment
      length polymorphism, and/or DNA sequencing) in order to evaluate the test and to
      define the cut off values, specificity, and sensitivity. RESULTS: The 14 biopsy
      samples in which H pylori was not detected did not give a positive result in any
      assay, and the 14 samples harbouring strains susceptible to clarithromycin gave a
      positive result with the wild type probe as expected. The 33 biopsy specimens
      containing resistant strains always gave a positive signal with one of the probes
      detecting resistant organisms, but in eight cases they also reacted with the wild
      type probe, indicating that a mixture of resistant and susceptible organisms was
      present. CONCLUSION: The importance of this new assay is that it allows the
      detection of multiple genotypes corresponding to either heterogeneous genotypes
      or mixed infections. Moreover, it allows in a single step not only the detection
      of H pylori but also the determination of its susceptibility to clarithromycin
      directly in biopsy specimens without the need for culture.

PMID- 10075952
TI  - Helicobacter pylori infection potentiates the inhibition of gastric acid
      secretion by omeprazole.
AB  - BACKGROUND: Omeprazole has a greater intragastric pH elevating effect in
      Helicobacter pylori positive than negative subjects. Ammonia production by H
      pylori has been suggested as a probable mechanism. AIMS: To assess the effect of
      H pylori status on gastric acid secretion during omeprazole treatment, and to
      examine the possible role of ammonia neutralisation of intragastric acid in
      increased omeprazole efficacy in infected subjects. METHODS: Twenty H pylori
      positive and 12 H pylori negative healthy volunteers were examined before and six
      to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma
      gastrin and acid output were measured basally and in response to increasing doses
      of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured.
      RESULTS: Prior to omeprazole, measurements were similar in the H pylori positive
      and negative subjects. During omeprazole, median basal intragastric pH was higher
      in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During
      omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800
      pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h
      respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for
      each). This effect was not explained by neutralisation by ammonia. CONCLUSION:
      The presence of H pylori infection leads to a more profound suppression of acid
      secretion during omeprazole treatment. The effect cannot be explained by
      neutralisation of intragastric acid by bacterial ammonia production and its
      precise mechanism has to be explained.

PMID- 10075953
TI  - The effect of hiatus hernia on gastro-oesophageal junction pressure.
AB  - BACKGROUND: Hiatus hernia and lower oesophageal sphincter hypotension are often
      viewed as opposing hypotheses for gastro-oesophageal junction incompetence. AIMS:
      To examine the interaction between hiatus hernia and lower oesophageal sphincter
      hypotension. METHODS: In seven normal subjects and seven patients with hiatus
      hernia, the squamocolumnar junction and intragastric margin of the gastro
      oesophageal junction were marked with endoscopically placed clips. Axial and
      radial characteristics of the gastro-oesophageal junction high pressure zone were
      mapped relative to the hiatus and clips during concurrent fluoroscopy and
      manometry. Responses to inspiration and abdominal compression were also analysed.
      RESULTS: In normal individuals the squamocolumnar junction was 0.5 cm below the
      hiatus and the gastro-oesophageal junction high pressure zone extended 1.1 cm
      distal to that. In those with hiatus hernia, the gastro-oesophageal junction high
      pressure zone had two discrete segments, one proximal to the squamocolumnar
      junction and one distal, attributable to the extrinsic compression within the
      hiatal canal. Inspiration and abdominal compression mainly augmented the distal
      one. Simulation of hernia reduction by algebraically summing the proximal segment
      pressures with the hiatal canal pressures restored normal maximal pressure,
      radial asymmetry, and dynamic responses of the gastro-oesophageal junction.
      CONCLUSIONS: Hiatus hernia reduces lower oesophageal sphincter pressure and
      alters its dynamic responsiveness by spatially separating pressure components
      derived from the intrinsic lower oesophageal sphincter and the extrinsic
      compression of the oesophagus within the hiatal canal.

PMID- 10075954
TI  - Geography of intestinal permeability and absorption.
AB  - BACKGROUND: Intestinal morphology and function vary geographically. AIMS: These
      functions were assessed in asymptomatic volunteers in European, North American,
      Middle Eastern, Asian, African, and Caribbean countries. METHODS: Five hour urine
      collections were obtained from each subject following ingestion of a 100 ml iso
      osmolar test solution containing 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and
      lactulose after an overnight fast, to assess active (3-0-methyl-D-glucose) and
      passive (D-xylose) carrier mediated, and non-mediated (L-rhamnose) absorption
      capacity, as well as intestinal permeability (lactulose:rhamnose ratio). RESULTS:
      A comparison of results for subjects from tropical countries (n=218) with those
      resident in the combined temperate and subtropical region (Europe, United States,
      Qatar) (n=224) showed significant differences. Residents in tropical areas had a
      higher mean lactulose:rhamnose ratio and lower mean five hour recoveries of 3-0
      methyl-D-glucose, D-xylose, and L-rhamnose, indicating higher intestinal
      permeability and lower absorptive capacity. Investigation of visiting residents
      suggested that differences in intestinal permeability and absorptive capacity
      were related to the area of residence. Subjects from Texas and Qatar, although
      comprised of several ethnic groups and resident in a subtropical area, showed no
      significant difference from European subjects. CONCLUSIONS: There are clearly
      demarcated variations in intestinal permeability and absorptive capacity
      affecting asymptomatic residents of different geographical areas which correspond
      with the condition described as tropical enteropathy. Results suggest the
      importance of environmental factors. The parameters investigated may be relevant
      to the predisposition of the indigenous population and travellers to diarrhoeal
      illness and malnutrition. Intestinal function in patients from the tropics may be
      difficult to interpret, but should take into account the range of values found in
      the asymptomatic normal population.

PMID- 10075955
TI  - Acute increase, stimulated by prostaglandin E2, in glucose absorption via the
      sodium dependent glucose transporter-1 in rat intestine.
AB  - BACKGROUND/AIMS: Acute stimulation by cAMP of the sodium dependent glucose
      cotransporter SGLT1 has previously been shown. As prostaglandin E2 (PGE2)
      increases intracellular cAMP concentrations via its receptor subtypes EP2R and
      EP4R, it was investigated whether PGE2 could enhance intestinal glucose
      absorption. METHODS: The action of PGE2 on carbohydrate absorption in the ex situ
      perfused rat small intestine and on 3-O-[14C]methylglucose uptake in isolated
      villus tip enterocytes was determined. Expression of mRNA for the PGE2 receptor
      subtypes 1-4 was assayed in enterocytes by reverse transcriptase polymerase chain
      reaction (RT-PCR). RESULTS: In the perfused small intestine, PGE2 acutely
      increased absorption of glucose and galactose, but not fructose (which is not a
      substrate for SGLT1); in isolated enterocytes it stimulated 3-O
      [14C]methylglucose uptake. The 3-O-[14C]methylglucose uptake could be inhibited
      by the cAMP antagonist RpcAMPS and the specific inhibitor of SGLT1, phlorizin.
      High levels of EP2R mRNA and EP4R mRNA were detected in villus tip enterocytes.
      CONCLUSION: PGE2 acutely increased glucose and galactose absorption by the small
      intestine via the SGLT1, with cAMP serving as the second messenger. PGE2 acted
      directly on the enterocytes, as the stimulation was still observed in isolated
      enterocytes and RT-PCR detected mRNA for the cAMP-increasing PGE2 receptors EP2R
      and EP4R.

PMID- 10075956
TI  - Involvement of tachykinin receptors in sensitisation to cow's milk proteins in
      guinea pigs.
AB  - BACKGROUND: There is growing evidence for a pivotal role for tachykinins in gut
      neuroimmune interactions. AIMS: To determine whether NK1, NK2, and NK3 tachykinin
      receptors are involved in milk protein induced allergic sensitisation. METHODS:
      Eight groups of 12 Dunkin-Hartley guinea pigs (250-300 g) were used. Four groups
      were sensitised to milk proteins for three weeks. During this period, these
      animals were injected intraperitoneally each day with NK1 (SR 140333; 0.3 mg/kg),
      NK2 (SR 48968; 5 mg/kg), or NK3 (SR 142801; 5 mg/kg) receptor antagonist or
      vehicle. The fifth group had water available instead of milk and was used as a
      non-sensitised control. The three other groups received the NK receptor
      antagonists for three weeks but were not sensitised to milk proteins. RESULTS:
      Sensitised animals treated with NK1 and NK3 receptor antagonists had both lower
      IgE and IgG serum titres, evaluated by passive cutaneous anaphylaxis, and lower
      specific IgG serum titres, determined by enzyme linked immunosorbent assay
      (ELISA), than vehicle treated animals. Sensitisation induced an increase in
      intestinal mast cell number which was abolished by treatment with the NK1
      receptor antagonist. Antigenic challenge-induced jejunal hypersecretion was also
      blocked by treatment with the NK1 receptor antagonist. CONCLUSION: In guinea
      pigs, NK1 and NK3 but not NK2 receptors are involved in sensitisation to cow's
      milk. However, NK1 but not NK3 receptor antagonists abolish both the
      hypermastocytosis induced by food allergy and the hypersecretion induced by
      antigenic challenge, suggesting different roles for NK1 and NK3 receptors in the
      mechanisms of sensitisation to beta-lactoglobulin.

PMID- 10075957
TI  - Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro.
AB  - BACKGROUND: Strains of Bacteroides fragilis producing a 20 kDa protein toxin (B
      fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and
      humans. Although in vitro results indicate that BFT damages intestinal epithelial
      cells in culture, the effects of BFT on native human colon are not known. AIMS:
      To examine the electrophysiological and morphological effects of purified BFT-2
      on human colonic mucosa in vitro. METHODS: For resistance (R) measurements,
      colonic mucosa mounted in Ussing chambers was exposed to luminal or serosal BFT-2
      (1.25-10 nM) and after four hours morphological damage was measured on
      haematoxylin and eosin stained sections using morphometry. F actin distribution
      was assessed using confocal microscopy. RESULTS: Serosal BFT-2 for four hours was
      four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing
      resistance, increasing epithelial 3H-mannitol permeability, and damaging crypt
      and surface colonocytes, respectively (p<0.05). Confocal microscopy showed
      reduced colonocyte F actin staining intensity after exposure to BFT-2.
      CONCLUSIONS: BFT-2 increases human colonic permeability and damages human colonic
      epithelial cells in vitro. These effects may be important in the development of
      diarrhoea and intestinal inflammation caused by B fragilis in vivo.

PMID- 10075958
TI  - Clinical spectral characterisation of colonic mucosal lesions using
      autofluorescence and delta aminolevulinic acid sensitisation.
AB  - BACKGROUND AND AIMS: Laser induced fluorescence (LIF) from colonic mucosa was
      measured in vivo with and without delta aminolevulinic acid (ALA) in an attempt
      to differentiate between neoplasia and non-neoplasia in real time during
      colonoscopy. METHODS: Spectra from 32 adenomas, 68 normal sites, and 14
      hyperplastic polyps in 41 patients were obtained with a point monitoring system.
      Twenty one of the patients had been given a low dose of ALA as a photosensitiser
      before the examination. Light of 337, 405, or 436 nm wavelength was used as
      excitation. Stepwise multivariate linear regression analysis was performed.
      RESULTS: With 337 nm excitation, 100% sensitivity and 96% specificity was
      obtained between normal mucosa and adenomas. Seventy seven per cent of the
      hyperplastic polyps were classified as non-neoplastic. When exciting with 405 and
      436 nm, the possibility of distinguishing different types of tissue was
      considerably better in the ALA patients than in the non-ALA patients.
      CONCLUSIONS: The in vivo point measurements imply that a good discrimination
      between normal tissue and adenomatous polyps can be obtained using the LIF
      technique. Excitation at 337 nm and at 405 nm or 436 nm using ALA gives good
      results. LIF also shows potential for distinguishing adenomatous from
      hyperplastic polyps. The number of detection wavelengths could be reduced if
      chosen properly.

PMID- 10075959
TI  - Linkage of Crohn's disease to the major histocompatibility complex region is
      detected by multiple non-parametric analyses.
AB  - BACKGROUND: There is evidence for genetic susceptibility to Crohn's disease, and
      a tentative association with tumour necrosis factor (TNF) and HLA class II
      alleles. AIMS: To examine the potential of genetic linkage between Crohn's
      disease and the MHC region on chromosome 6p. METHODS: TNF microsatellite markers
      and, for some families, additional HLA antigens were typed for 323 individuals
      from 49 Crohn's disease multiplex families to generate informative haplotypes.
      Non-parametric linkage analysis methods, including sib pair and affected relative
      pair methods, were used. RESULTS: Increased sharing of haplotypes was observed in
      affected sib pairs: 92% (48/52) shared one or two haplotypes versus an expected
      75% if linkage did not exist (p=0.004). After other affected relative pairs were
      included, the significance level reached 0.001. The mean proportion of haplotype
      sharing was increased for both concordant affected (pi=0.60, p=0.002) and
      unaffected sib pairs (pi=0.58, p=0. 031) compared with the expected value
      (pi=0.5). In contrast, sharing in discordant sib pairs was significantly
      decreased (pi=0.42, p=0. 007). Linear regression analysis using all three types
      of sib pairs yielded a slope of -0.38 at p=0.00003. It seemed that the HLA effect
      was stronger in non-Jewish families than in Jewish families. CONCLUSIONS: All
      available analytical methods support linkage of Crohn's disease to the MHC region
      in these Crohn's disease families. This region is estimated to contribute
      approximately 10-33% of the total genetic risk to Crohn's disease.

PMID- 10075960
TI  - Validation of a specific quality of life questionnaire for functional digestive
      disorders.
AB  - BACKGROUND: Dyspepsia and irritable bowel syndrome are suitable conditions for
      assessment of quality of life. Their similarities justify the elaboration of a
      single specific questionnaire for the two conditions. AIMS: To examine the
      process leading to the validation of the psychometric properties of the
      functional digestive disorders quality of life questionnaire (FDDQL). METHODS:
      Initially, the questionnaire was given to 154 patients, to assess its
      acceptability and reproducibility, analyse its content, and reduce the number of
      items. Its responsiveness was tested during two therapeutic trials which included
      428 patients. The questionnaire has been translated into French, English, and
      German. The psychometric validation study was conducted in France, United
      Kingdom, and Germany by 187 practitioners. A total of 401 patients with dyspepsia
      or irritable bowel syndrome, defined by the Rome criteria, filled in the FDDQL
      and generic SF-36 questionnaires. RESULTS: The structure of the FDDQL scales was
      checked by factorial analysis. Its reliability was expressed by a Cronbach's
      alpha coefficient of 0.94. Assessment of its discriminant validity showed that
      the more severe the functional digestive disorders, the more impaired the quality
      of life (p<0.05). Concurrent validity was supported by the correlation found
      between the FDDQL and SF-36 questionnaire scales. The final version of the
      questionnaire contains 43 items belonging to eight domains. CONCLUSIONS: The
      properties of the FDDQL questionnaire, available in French, English, and German,
      make it appropriate for use in clinical trials designed to evaluate its
      responsiveness to treatment among patients with dyspepsia and irritable bowel
      syndrome.

PMID- 10075961
TI  - Pancreatic stellate cells are activated by proinflammatory cytokines:
      implications for pancreatic fibrogenesis.
AB  - BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver,
      stellate cells play a major role in fibrogenesis by synthesising increased
      amounts of collagen and other extracellular matrix (ECM) proteins when activated
      by profibrogenic mediators such as cytokines and oxidant stress. AIMS: To
      determine whether cultured rat pancreatic stellate cells produce collagen and
      other ECM proteins, and exhibit signs of activation when exposed to the cytokines
      platelet derived growth factor (PDGF) or transforming growth factor beta (TGF
      beta). METHODS: Cultured pancreatic stellate cells were immunostained for the ECM
      proteins procollagen III, collagen I, laminin, and fibronectin using specific
      polyclonal antibodies. For cytokine studies, triplicate wells of cells were
      incubated with increasing concentrations of PDGF or TGF-beta. RESULTS: Cultured
      pancreatic stellate cells stained strongly positive for all ECM proteins tested.
      Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose
      related increase in cell counts as well as in the incorporation of 3H-thymidine
      into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose
      dependent increase in alpha smooth muscle actin expression and increased collagen
      synthesis. In addition, TGF-beta increased the expression of PDGF receptors on
      stellate cells. CONCLUSIONS: Pancreatic stellate cells produce collagen and other
      extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by
      increased proliferation and increased collagen synthesis. These results suggest
      an important role for stellate cells in pancreatic fibrogenesis.

PMID- 10075962
TI  - Underestimation of acute pancreatitis: patients with only a small increase in
      amylase/lipase levels can also have or develop severe acute pancreatitis.
AB  - BACKGROUND: In most treatment studies on acute pancreatitis, pancreatologists
      base their diagnosis on amylase/lipase levels more than three times above the
      upper limit of normal (>3n) and thus exclude patients with smaller enzyme level
      increases. The recommendations derived from the results of treatment studies do
      not take into account such patients. Non-pancreatologists frequently believe that
      only patients with high enzyme levels have a serious prognosis. AIMS: To question
      the assumption that high enzyme levels indicate severe, and conversely low enzyme
      levels indicate mild, acute pancreatitis. PATIENTS/METHODS: This retrospective
      study includes 284 consecutive patients with a first attack of acute
      pancreatitis. The cause was biliary in 114 (40%) patients, alcoholism in 83
      (29%), other in 21 (7%), and unknown in 66 (23%). Patients were divided into two
      groups according to their serum enzyme levels (amylase: </=3n, n = 88; >3n, n =
      196; lipase: </=3n, n = 51; >3n, n = 233). Renal impairment, indication for
      dialysis and artificial ventilation, development of pseudocysts, necessity for
      surgery, and mortality were taken as parameters of severity. RESULTS: The
      incidence of severity was the same for both the </=3n and >3n groups.
      CONCLUSIONS: The severity of acute pancreatitis is independent of the elevation
      in serum amylase/lipase level (</=3n or >3n) on admission. Patients with only a
      slight increase can also have or develop severe acute pancreatitis. Patients with
      </=3n elevated enzyme levels on admission represent a substantial group that
      treatment studies have frequently overlooked. This is especially true for
      patients with alcohol induced acute pancreatitis whose amylase levels are lower
      than in other aetiological groups.

PMID- 10075963
TI  - Immunoreactive pancreatic Reg protein in sera from cystic fibrosis patients with
      and without pancreatic insufficiency.
AB  - BACKGROUND: The biological function of the Reg protein, a non-enzymic protein
      produced in fairly large amounts by pancreatic acinar cells, remains elusive. Its
      susceptibility to proteolysis leading to precipitation of the proteolysis product
      at neutral pH suggests that it could contribute to the protein plugging observed
      in cystic fibrosis (CF). AIMS: To study its behaviour in the serum of CF patients
      with or without pancreatic insufficiency and to compare it with that of other
      pancreatic secretory proteins. PATIENTS: 170 patients (93 with CF, 55 controls,
      and 22 with chronic pancreatitis) were studied. METHODS: Reg protein was measured
      using a specific enzyme immunoassay and its molecular form in CF sera was
      characterised by gel filtration. Molecular gene expression was investigated by
      dot-blot hybridisation. RESULTS: Reg protein was present in all CF sera studied
      from patients with or without pancreatic insufficiency, and in all cases the
      level was significantly higher than in controls. Its chromatographic behaviour in
      CF sera was identical with that of the protein present in normal serum. No
      correlation was found between the levels of Reg protein and trypsin(ogen) (or
      lipase) in CF, nor in control sera or normal pancreatic juice. Molecular gene
      expression of the corresponding proteins investigated in pancreatic tissues
      showed an absence of correlation between the mRNA levels. CONCLUSIONS: Reg
      protein may not be a secretory exocrine protein like the digestive enzymes but
      rather a hormone-like secretory substance with an endocrine or paracrine
      function.

PMID- 10075964
TI  - Effect of long term simvastatin administration as an adjunct to ursodeoxycholic
      acid: evidence for a synergistic effect on biliary bile acid composition but not
      on serum lipids in humans.
AB  - BACKGROUND: Stimulated bile acid synthesis preferentially utilises newly
      synthesised cholesterol, raising the possibility that combination of simvastatin
      (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a
      stimulator of bile acid synthesis) may result in reduced bile acid synthesis and
      greater enrichment of the pool with UDCA than that achieved with UDCA treatment
      alone. AIMS: To investigate the effect of simvastatin and UDCA given alone and in
      combination on serum and biliary lipid and biliary bile acid composition.
      METHODS: Eighteen patients with primary non-familial hypercholesterolaemia were
      studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a
      combination of the two drugs. Each regimen was given in random order for three
      months following a three month lead in period. RESULTS: Simvastatin significantly
      reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol
      concentration remained unchanged. Combination of the two drugs had no synergistic
      effect on serum cholesterol concentration, but significantly increased the
      proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during
      combination treatment (p<0.04). CONCLUSIONS: Results showed that: (1) simvastatin
      reduces serum LDL cholesterol but has no effect on biliary cholesterol
      concentration, supporting the concept that newly synthesised cholesterol is not
      the preferential source for biliary cholesterol; and (2) combination of
      simvastatin with UDCA has the predicted effect of enhancing the proportion of
      UDCA in the pool. This effect may be of benefit in the treatment of cholestatic
      liver diseases.

PMID- 10075965
TI  - The role of apolipoprotein E and glucose intolerance in gallstone disease in
      middle aged subjects.
AB  - BACKGROUND: The polymorphism of apolipoprotein E has been suggested to be
      associated with the cholesterol content of gallstones, the crystallisation rate
      of gall bladder bile, and the prevalence of gallstone disease (GSD). AIMS: To
      investigate whether apolipoprotein E polymorphism modulates the susceptibility to
      GSD at the population level and to study the possible associations between
      impaired glucose tolerance, diabetes, and GSD. METHODS: Apolipoprotein E
      phenotypes were determined in a middle aged cohort of 261 randomly selected
      hypertensive men, 259 control men, 257 hypertensive women, and 267 control women.
      All subjects without a documented history of diabetes were submitted to a two
      hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography.
      RESULTS: In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared
      with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0. 28 (95%
      confidence interval 0.08-0.92). There was no protective effect in men. The
      relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7)
      for hypertensive men. In a stepwise multiple logistic regression model, E2
      protected against GSD in women, whereas two hour blood glucose in the OGTT, serum
      insulin, and plasma triglycerides were risk factors. Elevated blood glucose
      during the OGTT was also a significant risk factor for GSD in men. CONCLUSIONS:
      The data suggest that apolipoprotein E2 is a genetic factor providing protection
      against GSD in women. In contrast, impaired glucose tolerance and frank diabetes
      are associated with the risk of GSD.

PMID- 10075966
TI  - The natural course of hepatitis C virus infection 18 years after an epidemic
      outbreak of non-A, non-B hepatitis in a plasmapheresis centre.
AB  - BACKGROUND: The natural history of hepatitis C virus (HCV) infection is variable
      and factors determining the course of the illness are unclear. AIMS: To determine
      the natural course of HCV infection in a well characterised group of patients 18
      years after an epidemic outbreak of non-A, non-B hepatitis at a plasmapheresis
      centre. METHODS: Between 1994 and 1996, 20 of 30 affected individuals were
      studied. HCV infection was confirmed using second and third generation ELISA test
      kits. HCV RNA was detected by a polymerase chain reaction (PCR) method and HCV
      genotyping was performed by analysing amplicons from the conserved 5'-non
      translated region generated by nested PCR. Thirty two liver biopsies were carried
      out in 14 patients. RESULTS: HCV antibodies were detected in all subjects.
      Eighteen patients had abnormal liver enzymes and 17 were HCV RNA positive, all of
      whom were infected with genotype 1a. Ninety per cent of this cohort showed
      evidence of chronic HCV infection with 50% having progressive liver disease and
      20% cirrhosis 18 years after acute onset of non-A, non-B hepatitis. Considerable
      variation in disease outcome occurred between individuals and no correlation with
      clinical features of the acute illness was found. CONCLUSIONS: Variability in the
      consequences of HCV infection in cases infected with the same virus suggests that
      host factors are important in determining disease outcome. The factors which
      determine differences in the natural history of the disease still remain to be
      elucidated.

PMID- 10075967
TI  - Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic
      vein angioplasty and surgical shunting.
AB  - BACKGROUND: The role of percutaneous hepatic vein angioplasty in the management
      of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our
      unit, we have often used this technique in cases of short length hepatic vein
      stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse
      hepatic vein occlusion or failed angioplasty. AIMS: To review the outcome of
      angioplasty and surgical shunting to define their respective roles. PATIENTS: All
      patients treated by angioplasty or surgical shunting for non-malignant hepatic
      vein obstruction over a ten year period from 1987 to 1996. METHODS: A case note
      review of pretreatment features and clinical outcome. RESULTS: Angioplasty was
      attempted in 21 patients with patent hepatic vein branches and was successful in
      18; in three patients treatment was unsuccessful and these patients had surgical
      shunts. Fifteen patients were treated by surgical shunting only. Mortality
      according to definitive treatment was 3/18 following angioplasty and 8/18
      following surgery; in most cases this reflected high risk status prior to
      treatment. Venous or shunt reocclusion rates were similar for both groups and
      were associated with subtherapeutic warfarin in half of these cases. Most
      surviving patients in both groups are asymptomatic although one surgical patient
      has chronic hepatic encephalopathy. CONCLUSION: With appropriate case selection,
      many patients with Budd-Chiari syndrome caused by short length hepatic vein
      stenosis or occlusion may be managed successfully by angioplasty alone. Medium
      term outcome is good following this procedure provided that anticoagulation is
      maintained. Further follow up is required to assess for definitive benefits but
      we suggest that this should be included as a valid initial approach in the
      algorithm for management of Budd-Chiari syndrome.

PMID- 10075968
TI  - Hepatitis C virus recurrence after liver transplantation.
AB  - Cirrhosis due to hepatitis C virus (HCV) is now the most common indication of
      liver transplantation in Western Europe and the United States. In the absence of
      effective prophylaxis, recurrent HCV infection is almost inevitable. Though the
      natural history and intermediate term outcome of recurrent HCV are now better
      documented, those factors which may influence the recurrence of hepatitis and
      consequent progression of graft disease remain unclear. Interferon (IFN) as a
      sole agent for the treatment of recurrent infection has proved unsatisfactory.
      Early intervention with a combination of IFN and ribavirin seems promising, and
      this approach may prevent or delay progression of HCV related graft disease after
      liver transplantation.

PMID- 10075972
TI  - Recognition of the major histocompatibility complex restriction element modulates
      CD8(+) T cell specificity and compensates for loss of T cell receptor contacts
      with the specific peptide.
AB  - Triggering of a T cell requires interaction between its specific receptor (TCR)
      and a peptide antigen presented by a self-major histocompatibility complex (MHC)
      molecule. TCR recognition of self-MHC by itself falls below the threshold of
      detection in most systems due to low affinity. To study this interaction, we have
      used a read-out system in which antigen-specific effector T cells are confronted
      with targets expressing high levels of MHC compared with the selecting and
      priming environment. More specifically, the system is based on CD8(+) T cells
      selected in an environment with subnormal levels of MHC class I in the absence of
      beta2-microglobulin. We observe that the MHC restriction element can trigger
      viral peptide-specific T cells independently of the peptide ligand, provided
      there is an increase in self-MHC density. Peptide-independent triggering required
      at least four times the natural in vivo level of MHC expression. Furthermore,
      recognition of the restriction element at expression levels below this threshold
      was still enough to compensate for lack of affinity to peptides carrying alanine
      substitutions in major TCR contact residues. Thus, the specificity in TCR
      recognition and T cell activation is fine tuned by the avidity for self-MHC, and
      TCR avidities for peptide and MHC may substitute for each other. These results
      demonstrate a functional role for TCR avidity for self-MHC in tuning of T cell
      specificity, and support a role for cross-reactivity on "self" during T cell
      selection and activation.

PMID- 10075973
TI  - Modulation of proteasomal activity required for the generation of a cytotoxic T
      lymphocyte-defined peptide derived from the tumor antigen MAGE-3.
AB  - We have analyzed the presentation of human histocompatability leukocyte antigen
      A*0201-associated tumor peptide antigen MAGE-3271-279 by melanoma cells. We show
      that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a
      minigene encoding the preprocessed fragment MAGE-3271-279 failed to recognize
      cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides
      extended at the NH2 or COOH terminus of MAGE-3271-279 with purified human
      proteasome revealed that the generation of the COOH terminus of the antigenic
      peptide was impaired. Surprisingly, addition of lactacystin to purified
      proteasome, though partially inhibitory, resulted in the generation of the
      antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3
      protein with lactacystin resulted in efficient lysis by MAGE-3271-279-specific
      CTL. We therefore postulate that the generation of antigenic peptides by the
      proteasome in cells can be modulated by the selective inhibition of certain of
      its enzymaticactivities.

PMID- 10075974
TI  - An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation
      and characterization.
AB  - Staphylococcus epidermidis releases factors that activate the HIV-1 long terminal
      repeat, induce cytokine release, and activate nuclear factor B in cells of
      macrophage lineage. The active material had a mass of 34,500 daltons, was
      inactivated by proteases and partitioned into the phenol layer on hot aqueous
      phenol extraction, and thus was termed phenol-soluble modulin (PSM). High
      performance liquid chromatography (HPLC) of crude PSM yielded two peaks of
      activity designated PSM peak 1 and peak 2. MALDI-TOF (matrix-assisted laser
      desorption ionization-time of flight) mass spectroscopy indicated the presence of
      two components in peak 1, which were designated PSM and PSM. Peak 2 contained a
      single component, designated PSM. Separation of PSM and PSM in peak 1 could be
      achieved by a second HPLC procedure. The structure of each component was
      determined by amino acid sequence analysis and identification and sequencing of
      their genes. PSM, PSM, and PSM were 22-, 44-, and 25-amino acid, respectively,
      strongly hydrophobic polypeptides. PSM was identified as Staphylococcus
      epidermidis delta toxin, whereas PSM and PSM exhibited more distant homology to
      previously described staphylococcal toxins. They appeared to exist as a complex
      or aggregate with activity greater than the component parts. The properties of
      the S. epidermidis PSMs suggest that they may contribute to the systemic
      manifestations of Gram-positive sepsis.

PMID- 10075975
TI  - B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4
      dependent mechanism.
AB  - For T cells to become functionally activated they require at least two signals.
      The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal
      for T cell activation. In this report, we studied the relative roles of B7-1 and
      B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4.
      We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by
      transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are
      completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we find that EL4-B7
      2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4
      double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1
      tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not
      rejected when implanted into syngeneic mice but progressively grew to produce
      tumors. The double transfectant EL4 cells could costimulate T cell proliferation
      that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4
      immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4
      cells were functional. In vivo, treatment of mice implanted with double
      transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor
      rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild
      type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data
      suggests that B7-2 expressed on some T cell tumors inhibits development of
      antitumor immunity, and IL-4 appears to play a critical role in abrogation of the
      antitumor immune response.

PMID- 10075976
TI  - Essential role of P-selectin in the initiation of the inflammatory response
      induced by hemorrhage and reinfusion.
AB  - Resuscitation from hemorrhage induces profound pathophysiologic alterations and
      activates inflammatory cascades able to initiate neutrophil accumulation in a
      variety of tissues. This process is accompanied by acute organ damage (e.g.,
      lungs and liver). We have previously demonstrated that significant leukocyte
      endothelium interactions occur very early in other forms of ischemia/reperfusion
      (i.e., splanchnic ischemia/reperfusion and traumatic shock) which are largely
      mediated by increased expression of the adhesion molecule, P-selectin, on the
      vascular endothelium. Here we postulated that increased endothelial expression of
      P-selectin in the microvasculature would play an essential role in initiating the
      inflammatory signaling of hemorrhagic shock. Using intravital microscopy, we
      found that hemorrhagic shock significantly increased the number of rolling and
      adherent leukocytes in the mouse splanchnic microcirculation. In contrast, mice
      genetically deficient in P-selectin, or wild-type mice given either an anti-P
      selectin monoclonal antibody or a recombinant soluble P-selectin glycoprotein
      ligand (PSGL)-1 immunoglobulin, exhibited markedly attenuated leukocyte
      endothelium interaction after hemorrhagic shock. Thus, activation of P-selectin
      protein on the microvascular endothelium is essential for the initial
      upregulation of the inflammatory response occurring in hemorrhagic shock.
      Moreover, endogenous levels of PSGL-1 mRNA were significantly increased in the
      lung, liver, and small intestine of wild-type mice subjected to hemorrhagic
      shock. Since PSGL-1 promotes adhesive interactions largely through P-selectin
      expressed on the vascular endothelium, this result further supports the crucial
      role played by P-selectin in the recruitment of leukocytes during hemorrhagic
      shock.

PMID- 10075977
TI  - Relevance of L-selectin shedding for leukocyte rolling in vivo.
AB  - The velocity of rolling leukocytes is thought to be determined by the expression
      of adhesion molecules and the prevailing wall shear stress. Here, we investigate
      whether rapid cleavage of L-selectin may be an additional physiologic regulatory
      parameter of leukocyte rolling. A unique protease in the membrane of leukocytes
      cleaves L-selectin after activation, resulting in L-selectin shedding. The
      hydroxamic acid-based metalloprotease inhibitor KD-IX-73-4 completely prevented L
      selectin shedding in vitro and significantly decreased the rolling velocity of
      leukocytes in untreated wild-type C57BL/6 mice from 55 to 35 micrometer/seconds
      in vivo. When E-selectin was expressed on the endothelium (tumor necrosis factor
      [TNF]-alpha treatment 2.5-3 h before the experiment), rolling velocity was 4
      micrometer/seconds and did not change after the application of KD-IX-73-4.
      However, KD-IX-73-4 decreased mean rolling velocity by 29% from 23 to 16
      micrometer/seconds in E-selectin-deficient mice treated with TNF-alpha. The
      reduction of velocity caused by KD-IX-73-4 was immediate (<5 s) after injection
      of KD-IX-73-4 as shown by a novel method using a local catheter. These results
      establish a role for L-selectin shedding in regulating leukocyte rolling velocity
      in vivo.

PMID- 10075978
TI  - A novel gene coding for a Fas apoptosis inhibitory molecule (FAIM) isolated from
      inducibly Fas-resistant B lymphocytes.
AB  - The sensitivity of primary splenic B cells to Fas-mediated apoptosis is modulated
      in a receptor-specific fashion. Here we used a differential display strategy to
      detect cDNAs present in B cells rendered Fas resistant but absent in those
      rendered Fas sensitive. This led to the cloning and characterization of a novel
      1.2-kb gene that encodes a Fas apoptosis inhibitory molecule (FAIM). faim
      transfected BAL-17 B lymphoma cells were less sensitive by half or more to Fas
      mediated apoptosis than were vector-transfected controls, using Fas ligand
      bearing T cells or a cytotoxic anti-Fas antibody to trigger Fas, and this was
      associated with inhibition of Fas- induced poly-ADP ribose polymerase (PARP)
      cleavage. In primary B cells, the time course of faim mRNA and FAIM protein
      expression correlated with the induction of Fas resistance by surface (s)Ig
      engagement. Thus, FAIM is an inducible effector molecule that mediates Fas
      resistance produced by sIg engagement in B cells. However, faim is broadly
      expressed in various tissues and the faim sequence is highly conserved
      evolutionarily, suggesting that its role extends beyond lymphocyte homeostasis.
      As FAIM has no significant regions of homology to other gene products that
      modulate Fas killing, it appears to represent a distinct, new class of
      antiapoptotic protein.

PMID- 10075979
TI  - The cyclin-dependent kinase Cdk2 regulates thymocyte apoptosis.
AB  - Aberrant activation of cell cycle molecules has been postulated to play a role in
      apoptosis ("catastrophic cell cycle"). Here we show that in noncycling developing
      thymocytes, the cyclin- dependent kinase Cdk2 is activated in response to all
      specific and nonspecific apoptotic stimuli tested, including peptide-specific
      thymocyte apoptosis. Cdk2 was found to function upstream of the tumor suppressor
      p53, transactivation of the death promoter Bax, alterations of mitochondrial
      permeability, Bcl-2, caspase activation, and caspase-dependent proteolytic
      cleavage of the retinoblastoma protein. Inhibition of Cdk2 completely protected
      thymocytes from apoptosis, mitochondrial changes, and caspase activation. These
      data provide the first evidence that Cdk2 activity is crucial for the induction
      of thymocyte apoptosis.

PMID- 10075980
TI  - Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous
      IL-12: a critical step in the differentiation of pathogenic autoreactive T cells.
AB  - The interleukin (IL)-12 receptor (R)beta2 subunit is the critical molecule
      involved in maintaining IL-12 responsiveness and controlling T helper cell type 1
      lineage commitment. We demonstrate that IL-12 and interferon (IFN)-gamma play
      separate, but complementary, roles in regulating IL-12Rbeta2 expression on
      antigen-specific CD4(+) T cells. These results are consistent with our previous
      observation that IL-12 can promote autoimmune disease through IFN-gamma
      independent as well as -dependent pathways. Therefore, we compared the induction
      of IL-12 by, and the expression of the IL-12Rbeta2 subunit on, myelin basic
      protein (MBP)-specific T cells from experimental allergic encephalomyelitis (EAE)
      susceptible SJL (H-2(s)) mice and from EAE- resistant B10.S mice (H-2(s)). B10.S
      mice had an antigen-specific defect in their capacity to upregulate the IL
      12Rbeta2 subunit. Defective expression was not secondary to the production of
      suppressive cytokines, but to a failure of B10.S MBP-specific T cells to
      upregulate CD40 ligand expression and to induce the production of IL-12. IL
      12Rbeta2 expression as well as encephalitogenicity of these cells could be
      restored by the addition of IL-12. These results suggest that the development of
      immunotherapies that target the IL-12Rbeta2 subunit may be useful for the
      treatment of autoimmune diseases.

PMID- 10075981
TI  - Characterization of the 4C8 antigen involved in transendothelial migration of
      CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell
      monolayers.
AB  - In extravasation of T cells, little is known about the mechanisms of
      transendothelial migration subsequent to the T cells' tight adhesion to
      endothelium. To investigate these mechanisms, we developed a monoclonal antibody
      (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture
      system in which high CD26-expressing (CD26(hi)) T cells preferentially migrate
      through human umbilical vein endothelial cell (HUVEC) monolayers cultured on
      collagen gels. Anti-4C8 reacted with all CD3(+) T cells and monocytes but not
      neutrophils or HUVECs. The structure defined by this antibody was an 80-kD
      molecule. The mAb at 1 mug/ml inhibited 80-90% of migration of CD3(+) T cells
      through unstimulated and interferon gamma-stimulated HUVEC monolayers without
      interfering with adhesion and cell motility. When added to the cultures after the
      adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T
      cells. Phase-contrast and electron microscopy revealed that T cells are arrested
      at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8
      exhibited agonistic effects on resting T cells without other stimuli under
      culture conditions in which anti-4C8 can stimulate T cells. First, in the
      checkerboard assay using collagen gels, the antibody promoted chemokinetic
      migration of the cells in a dose-dependent manner from 0.1 to 10 mug/ml. The
      predominant population of T cells that migrated into collagen gels with
      impregnated anti-4C8 were CD26(hi). Second, solid-phase-immobilized anti-4C8
      induced adhesion of T cells to the substrate, often with polarizations in cell
      shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti
      4C8 augmented F-actin content preferentially in CD26(hi) T cells when added to T
      cells at a high dose of 10 mug/ml. Finally, both anti-4C8-induced chemokinetic
      migration and transendothelial migration were inhibited by pretreatment of T
      cells with pertussis toxin. These findings suggest that stimulation via the 4C8
      antigen increases cell motility of CD26(hi) cells with profound cytoskeletal
      changes through signaling pathways including G proteins. The 4C8 antigen may be
      involved in preferential transmigration of CD26(hi) cells adherent to HUVECs.

PMID- 10075982
TI  - Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian
      immunodeficiency virus-infected macaques.
AB  - To determine the role of CD8(+) T cells in controlling simian immunodeficiency
      virus (SIV) replication in vivo, we examined the effect of depleting this cell
      population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a
      99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta
      treated with OKT8F. The apparent CD8 depletion started 1 h after antibody
      administration, and low CD8 levels were maintained until day 8. An increase in
      plasma viremia of one to three orders of magnitude was observed in five of the
      six macaques. The injection of a control antibody to an infected macaque did not
      induce a sustained viral load increase, nor did it significantly reduce the
      number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial
      role in suppressing SIV replication in vivo.

PMID- 10075983
TI  - A critical role for the RelA subunit of nuclear factor kappaB in regulation of
      multiple immune-response genes and in Fas-induced cell death.
AB  - Binding sites for the nuclear factor (NF)-kappaB transcription factor have been
      identified within control regions of many genes involved in inflammatory and
      immune responses. Such kappaB sites are often found adjacent to those of
      interferon (IFN)-gamma-inducible transcription factors, suggesting a requirement
      for multiple signaling pathways for gene regulation. Using fibroblasts from RelA
      (p65)-deficient mice generated by gene targeting, we have investigated the role
      of this subunit of NF-kappaB in gene activation by microbial lipopolysaccharide,
      tumor necrosis factor alpha, and in possible synergism with the IFN-gamma
      signaling pathway. Our results indicate not only that RelA is required for
      activation of key genes involved in adaptive (acquired) immune responses,
      including major histocompatibility complex class I, CD40, and the Fas death
      receptor, but also that both NF-kappaB-inducing signals and IFN-gamma are
      necessary for maximal activation. In contrast, neutrophil-specific chemokine
      genes KC and MIP-2, which can function as nonspecific mediators in innate immune
      responses, were strongly induced by RelA in the absence of IFN-gamma. Our results
      show that RelA plays a critical role in activation of immune system genes in
      response to nonspecific stimuli and demonstrate a novel proapoptotic function for
      this protein in Fas-induced cell death.

PMID- 10075984
TI  - Transgenic interleukin 10 prevents induction of experimental autoimmune
      encephalomyelitis.
AB  - The effectiveness of interleukin 10 (IL-10) in the treatment of autoimmune
      mediated central nervous system inflammation is controversial. Studies of the
      model system, experimental autoimmune encephalomyelitis (EAE), using various
      routes, regimens, and delivery methods of IL-10 suggest that these variables may
      affect its immunoregulatory function. To study the influence of these factors on
      IL-10 regulation of EAE pathogenesis, we have analyzed transgenic mice expressing
      human IL-10 (hIL-10) transgene under the control of a class II major
      histocompatibility complex (MHC) promoter. The hIL-10 transgenic mice are highly
      resistant to EAE induced by active immunization, and this resistance appears to
      be mediated by suppression of autoreactive T cell function. Myelin-reactive T
      helper 1 cells are induced but nonpathogenic in the IL-10 transgenic mice.
      Antibody depletion confirmed that EAE resistance is dependent on the presence of
      the transgenic IL-10. Mice expressing the hIL-10 transgene but not the endogenous
      murine IL-10 gene demonstrated that transgenic IL-10 from MHC class II-expressing
      cells is sufficient to block induction of EAE. This study demonstrates that IL-10
      can prevent EAE completely if present at appropriate levels and times during
      disease induction.

PMID- 10075985
TI  - Resistance of CD7-deficient mice to lipopolysaccharide-induced shock syndromes.
AB  - CD7 is an immunoglobulin superfamily molecule involved in T and natural killer
      (NK) cell activation and cytokine production. CD7-deficient animals develop
      normally but have antigen-specific defects in interferon (IFN)-gamma production
      and CD8(+) CTL generation. To determine the in vivo role of CD7 in systems
      dependent on IFN-gamma, the response of CD7-deficient mice to lipopolysaccharide
      (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock
      model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control
      C57BL/6 mice survived LPS challenge (P < 0.001). CD7-deficient or C57BL/6 control
      mice were next injected with low-dose LPS (1 microgram plus 8 mg D-galactosamine
      [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive
      72 h after injection of LPS compared with 20% of C57BL/6 control mice (P <
      0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum
      IFN-gamma and tumor necrosis factor (TNF)-alpha levels compared with control
      C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN-gamma and TNF-alpha in
      liver tissue were also significantly decreased in CD7-deficient mice compared
      with controls (P < 0.05). In contrast, CD7-deficient animals had normal liver
      interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA
      levels, and CD7-deficient splenocytes had normal IFN-gamma responses when
      stimulated with IL-12 and IL-18 in vitro. NK1.1(+)/ CD3(+) T cells are known to
      be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of
      liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of
      liver NK1.1(+)/CD3(+) T cells (1.5 +/- 0.3 x 10(5)) versus C57BL/6 control mice
      (3.7 +/- 0.8 x 10(5); P < 0.05), whereas numbers of liver NK1.1(+)/CD3(-) NK
      cells were not different from controls. Thus, targeted disruption of CD7 leads to
      a selective deficiency of liver NK1.1(+)/ CD3(+) T cells, and is associated with
      resistance to LPS shock. These data suggest that CD7 is a key molecule in the
      inflammatory response leading to LPS-induced shock.

PMID- 10075986
TI  - Towards mixed sequence recognition by triple helix formation.
AB  - The formation of intermolecular DNA triple helices offers the possibility of
      designing compounds with extensive sequence recognition properties which may be
      useful as antigene agents or tools in molecular biology. One major limitation of
      this approach is that these structures are generally restricted to homo-purine.
      homopyrimidine target sites. This review describes the strategies that have been
      employed to overcome this drawback and outlines the potential for triplex
      formation at mixed sequence DNA targets.

PMID- 10075987
TI  - mRNAs have greater negative folding free energies than shuffled or codon choice
      randomized sequences.
AB  - An examination of 51 mRNA sequences in GenBank has revealed that calculated mRNA
      folding is more stable than expected by chance. Free energy minimization
      calculations of native mRNA sequences are more negative than randomized mRNA
      sequences with the same base composition and length. Randomization of the coding
      region of genes yields folding free energies of less negative magnitude than the
      original native mRNA sequence. Randomization of codon choice, while still
      preserving original base composition, also results in less stable mRNAs. This
      suggests that a bias in the selection of codons favors the potential formation of
      mRNA structures which contribute to folding stability.

PMID- 10075988
TI  - Kinetic selection of HPV 16 E6/E7-directed antisense nucleic acids: anti
      proliferative effects on HPV 16-transformed cells.
AB  - The E6/E7-coding sequences of the human papillomavirus type 16 (HPV 16) were
      probed for kinetic accessibility in vitro by pools of catalytic antisense RNA.
      Only long-chain complementary RNA and very few antisense sequences with a 3'
      portion complementary to a 10 nt window within unspliced and spliced E6-coding
      target sequences showed fast annealing with k(ass) values of up to 10(4) M-1s-1
      indicating that the majority of E6/E7 RNA sequences are unfavourable targets for
      antisense inhibitors and ribozymes. Fast-annealing antisense
      oligodeoxyribonucleotides directed against the window of 10 nt inhibited cell
      proliferation of HPV 16-transformed SiHa cells but not slow-annealing antisense
      species. Antisense RNA of several hundred nucleotides in length also showed
      significant anti-proliferative activity. Biological effects of antisense
      oligodeoxyribonucleotides were specific for the antisense sequence, could only be
      found in HPV-positive but not in HPV-negative cell lines, and were related to
      decreased levels of E7 protein and E6/E7-specific transcripts. This work suggests
      that HPV 16 E7/E6 sequences exhibit a low accessibility for antisense
      oligonucleotides. This can be overcome, however, by exploiting the relationship
      between fast annealing of antisense species and their increased efficacy in human
      cells.

PMID- 10075989
TI  - Structure of the oligonucleotide d(CGTATATACG) as a site-specific complex with
      nickel ions.
AB  - In this paper we explore the application of Ni2+to the crystallization of
      oligonucleotides. We have determined in this way the structure of a fully
      alternating (Y-R) decanucleotide d(CGTATATACG) by single crystal X-ray
      diffraction. This is the first oligonucleotide crystal structure with an
      alternating 5'-(TA)3-3' central part. Alternating oligonucleotides have a
      particular interest since they often have a unique structure. In this case the
      general conformation is B-like with an alternating twist and an end-to-end
      interaction which involves terminal guanines. The crystal belongs to space group
      P41212 with a = b = 52.46, c = 101.49 A. This packing imposes a 90 degrees
      crossing of the symmetry related helices. This is a new way of packing for
      decamers. The oligonucleotide structure is characterized by the specific
      association with seven nickel ions, involving the N7 atom of every guanine. One
      of the Ni2+ions is shared between two guanines of symmetry related molecules.
      Until now no oligonucleotide has been crystallized in the presence of this metal
      ion. A novel C.A.T triplet structure has also been tentatively identified.

PMID- 10075990
TI  - Initiation of DNA replication at the Chinese hamster origin oriGNAI3 relies on
      local sequences and/or chromatin structures, but not on transcription of the
      nearby GNAI3 gene.
AB  - We recently identified a region of preferential replication initiation, oriGNAI3,
      near the 3' end of the Chinese hamster GNAI3 gene. oriGNAI3 is co-amplified in
      mutants selected for AMPD2 amplification, a process generating chromosomal
      rearrangements. In this report we have taken advantage of cell lines with
      truncated and translocated amplified units to show that these rearrangements do
      not alter the function of ori GNAI3. These results indicate that replication
      initiation at this locus relies essentially on local features. Interestingly, the
      study of one line in which a rearrangement has disrupted the GNAI3 gene shows
      that ongoing transcription of this gene is not required for initiation at
      oriGNAI3. In order to obtain further insight into the sequences and/or chromatin
      structures required for oriGNAI3 function, we have analyzed the DNase I
      sensitivity and nucleotide sequence of the region. The features important for
      replication initiation appear to cluster in a 7-12 kb region which includes
      oriGNAI3.

PMID- 10075991
TI  - DNA polymerase beta-like nucleotidyltransferase superfamily: identification of
      three new families, classification and evolutionary history.
AB  - A detailed analysis of the polbeta superfamily of nucleotidyltransferases was
      performed using computer methods for iterative database search, multiple
      alignment, motif analysis and structural modeling. Three previously
      uncharacterized families of predicted nucleotidyltransferases are described. One
      of these new families includes small proteins found in all archaea and some
      bacteria that appear to consist of the minimal nucleotidyltransferase domain and
      may resemble the ancestral state of this superfamily. Another new family that is
      specifically related to eukaryotic polyA polymerases is typified by yeast Trf4p
      and Trf5p proteins that are involved in chromatin remodeling. The TRF family is
      represented by multiple members in all eukaryotes and may be involved in yet
      unknown nucleotide polymerization reactions required for maintenance of chromatin
      structure. Another new family of bacterial and archaeal nucleotidyltransferases
      is predicted to function in signal transduction since, in addition to the
      nucleotidyltransferase domain, these proteins contain ligand-binding domains. It
      is further shown that the catalytic domain of gamma proteobacterial adenylyl
      cyclases is homologous to the polbeta superfamily nucleotidyltransferases which
      emphasizes the general trend for the origin of signal-transducing enzymes from
      those involved in replication, repair and RNA processing. Classification of the
      polbeta superfamily into distinct families and examination of their phyletic
      distribution suggests that the evolution of this type of nucleotidyltransferases
      may have included bursts of rapid divergence linked to the emergence of new
      functions as well as a number of horizontal gene transfer events.

PMID- 10075992
TI  - DNA minor groove recognition by bis-benzimidazole analogues of Hoechst 33258:
      insights into structure-DNA affinity relationships assessed by fluorescence
      titration measurements.
AB  - Fluorescence titration measurements have been used to examine the binding
      interaction of a number of analogues of the bis -benzimidazole DNA minor groove
      binding agent Hoechst 33258 with the decamer duplex d(GCAAATTTGC)2. The method of
      continuous variation in ligand concentration (Job plot analysis) reveals a 1:1
      binding stoichiometry for all four analogues; binding constants are independent
      of drug concentration (in the range [ligand] = 0.1-5 microM). The four analogues
      studied were chosen in order to gain some insight into the relative importance of
      a number of key structural features for minor groove recognition, namely (i)
      steric bulk of the N -methylpiperazine ring, (ii) ligand hydrophobicity, (iii)
      isohelicity with the DNA minor groove and (iv) net ligand charge. This was
      achieved, first, by replacing the bulky, non-planar N -methylpiperazine ring with
      a less bulky planar charged imidazole ring permitting binding to a narrower
      groove, secondly, by linking the N -methylpiperazine ring to the phenyl end of
      the molecule to give the molecule a more linear, less isohelical conformation
      and, finally, by introducing a charged imidazole ring in place of the phenolic OH
      making it dicationic, enabling the contribution of the additional electrostatic
      interaction and extended conformation to be assessed. Delta G values were
      measured at 20 degrees C in the range -47.6 to -37.5 kJ mol-1 and at a number of
      pH values between 5.0 and 7.2. We find a very poor correlation between Delta G
      values determined by fluorescence titration and effects of ligand binding on DNA
      melting temperatures, concluding that isothermal titration methods provide the
      most reliable method of determining binding affinities. Our results indicate that
      the bulky N -methylpiperazine ring imparts a large favourable binding
      interaction, despite its apparent requirement for a wider minor groove, which
      others have suggested arises in a large part from the hydrophobic effect. The
      binding constant appears to be insensitive to the isohelical arrangement of the
      constituent rings which in these analogues gives the same register of hydrogen
      bonding interactions with the floor of the groove.

PMID- 10075993
TI  - Heavy de novo methylation at symmetrical and non-symmetrical sites is a hallmark
      of RNA-directed DNA methylation.
AB  - Previous analysis of potato spindle tuber viroid (PSTVd) RNA-infected tobacco
      plants has suggested that an RNA-DNA interaction could trigger de novo
      methylation of PSTVd transgene sequences. Using the genomic sequencing technique,
      the methylation pattern associated with the RNA-directed DNA methylation process
      has been characterized. Three different PSTVd transgene constructs all showed a
      similar pattern of methylation. Most of the cytosines at symmetrical as well as
      non-symmetrical positions appeared to be methylated in both DNA strands of the
      viroid sequences. Heavy methylation was mostly restricted to the viroid cDNA
      sequences. Flanking DNA regions immediately adjacent to the viroid cDNA displayed
      a lower but significant level of cytosine methylation. The observation that the
      heavy methylation was essentially co-extensive with the length of the PSTVd cDNA
      sequences provided evidence that a direct RNA-DNA interaction can act as a strong
      and highly specific signal for de novo DNA methylation. These data also confirmed
      that de novo methylation was not limited to canonical CpG and CpNpG sites, but
      can also involve all the cytosine residues located in the genomic region where
      the RNA-DNA interaction takes place.

PMID- 10075994
TI  - Orientation and positional mapping of the subunits of the multicomponent
      transcription factors RFX and X2BP to the major histocompatibility complex class
      II transcriptional enhancer.
AB  - Major histocompatibility complex class II genes contain a common complex enhancer
      that allows for their coordinate regulation. The X box element of the enhancer
      cooperatively binds the multisubunit transcription factors RFX and X2BP. RFX is
      an essential class II transcription factor and contains three distinct proteins:
      RFX5, RFX-B/Ank and RFXAP. X2BP, a CREB/ATF family transcription factor, most
      likely binds as a homodimer. A site-specific protein-DNA photocrosslinking assay
      was used to investigate the interactions of the subunits of RFX and X2BP with X
      box DNA. Two of the RFX subunits, RFX5 and RFX-B/Ank, were found to bind defined
      sites within the X1 half of the X box. The third RFX subunit, RFXAP, made
      extensive X1 box contacts. The subunits of X2BP made contacts with the edges of
      the X2 half of the X box in a manner consistent with other bZIP transcription
      factor contact patterns. The resulting map provides specific base pair contacts
      and subunit orientation with respect to the DNA sequence of the RFX-X2BP-X box
      complex. Our results suggest possible stoichiometry of the RFX subunits and
      potential interaction between RFX-B/Ank and RFXAP with one of the subunits of
      X2BP.

PMID- 10075995
TI  - Proteome composition and codon usage in spirochaetes: species-specific and DNA
      strand-specific mutational biases.
AB  - The genomes of the spirochaetes Borrelia burgdorferi and Treponema pallidum show
      strong strand-specific skews in nucleotide composition, with the leading strand
      in replication being richer in G and T than the lagging strand in both species.
      This mutation bias results in codon usage and amino acid composition patterns
      that are significantly different between genes encoded on the two strands, in
      both species. There are also substantial differences between the species, with
      T.pallidum having a much higher G+C content than B. burgdorferi. These changes in
      amino acid and codon compositions represent neutral sequence change that has been
      caused by strong strand- and species-specific mutation pressures. Genes that have
      been relocated between the leading and lagging strands since B. burgdorferi and
      T.pallidum diverged from a common ancestor now show codon and amino acid
      compositions typical of their current locations. There is no evidence that
      translational selection operates on codon usage in highly expressed genes in
      these species, and the primary influence on codon usage is whether a gene is
      transcribed in the same direction as replication, or opposite to it. The dnaA
      gene in both species has codon usage patterns distinctive of a lagging strand
      gene, indicating that the origin of replication lies downstream of this gene,
      possibly within dnaN. Our findings strongly suggest that gene-finding algorithms
      that ignore variability within the genome may be flawed.

PMID- 10075996
TI  - Trans-activation of the Tetrahymena group I intron ribozyme via a non-native RNA
      RNA interaction.
AB  - The peripheral P2.1 domain of the Tetrahymena group I intron ribozyme has been
      shown to be non-essential for splicing. We found, however, that separately
      prepared P2.1 RNA efficiently accelerates the 3' splice-site-specific hydrolysis
      reaction of a mutant ribozyme lacking both P2.1 and its upstream region in trans.
      We report here the unusual properties of this trans-activation. Compensatory
      mutational analysis revealed that non-native long-range base-pairings between the
      loop region of P2.1 RNA and L5c region of the mutant ribozyme are needed for the
      activation in spite of the fact that P2.1 forms base-pairings with P9.1 in the
      Tetrahymena ribozyme. The trans -activation depends on the non-native RNA-RNA
      interaction together with the higher order structure of P2.1 RNA. This activation
      is unique among the known trans-activations that utilize native tertiary
      interactions or RNA chaperons.

PMID- 10075997
TI  - The repressor which binds the -75 GATA motif of the GPB promoter contains Ku70 as
      the DNA binding subunit.
AB  - Glycophorin B (GPB) is an abundant cell surface glycoprotein which is only
      expressed in human erythroid cells. Previous functional analysis demonstrated
      that the repression of the GPB promoter is determined by the binding of a
      ubiquitous factor which recognizes a GATA motif centered at position -75. In
      erythroid cells this ubiquitous factor is displaced by the binding of the
      erythroid-specific factor hGATA1. Here, we have identified the Ku70 protein as a
      candidate GPB repressor DNA binding subunit through the screening of a human HeLa
      expression library using the -75 GATA sequence as bait (one-hybrid method).
      Electrophoretic mobility shift assays demonstrated that the ubiquitous factor
      that binds the -75 GATA sequence was the Ku70-Ku80 (Ku) heterodimer. Co
      transfection experiments demonstrated that overexpression of Ku70 in the K562
      erythroleukeamic cell line resulted in transcriptional repression of the
      chloramphenicol acetyltransferase reporter gene when placed under the control of
      the wild-type GPB promoter. Conversely, no repression was observed when a
      mutation that abolished the binding of Ku was introduced in the GPB promoter
      construct. Altogether, these results indicate that Ku binds in vivo to the -75
      WGATAR motif and is involved in negative regulation of the GPB promoter. These
      findings suggest that, besides its role in many functions, Ku is also involved in
      transcriptional regulation of erythroid genes.

PMID- 10075998
TI  - An AU-rich sequence in the 3'-UTR of plasminogen activator inhibitor type 2 (PAI
      2) mRNA promotes PAI-2 mRNA decay and provides a binding site for nuclear HuR.
AB  - The plasminogen activator inhibitor type 2 (PAI-2) gene is regulated by
      transcriptional and post-transcriptional processes. We have previously shown that
      insertion of the 3'-untranslated region (3'-UTR) of PAI-2 mRNA into the 3'-UTR of
      a beta-globin reporter mRNA reduces constitutive beta-globin mRNA expression and
      that this requires, at least in part, an AU-rich motif. Here we have directly
      assessed the role of this motif in PAI-2 mRNA stability using both chimeric and
      non-chimeric reporter systems. We first show that the full-length PAI-2 mRNA is
      indeed unstable with a half-life of 1 h. Using the c-fos promoter-driven human
      growth hormone (HGH) mRNA as a reporter, we demonstrate that the 580 nt 3'-UTR of
      PAI-2 accelerates chimeric HGH mRNA decay in a process which is dependent on the
      intact AU-rich sequence. Furthermore, disruption of this motif within a
      constitutively expressed PAI-2 cDNA produces a 2.5- and 2. 7-fold increase in PAI
      2 mRNA and protein levels in HT-1080 cells, respectively. RNA electrophoretic
      mobility shift and supershift assays indicate that this motif provides a specific
      binding site for cellular proteins that include nuclear HuR. Taken together,
      these data show that a correlation exists between the binding of HuR to the AU
      rich motif in vitro and the destabilizing properties conferred by this sequence
      in vivo.

PMID- 10075999
TI  - Long-term stability of large insert genomic DNA episomal shuttle vectors in human
      cells.
AB  - We have constructed an episomal shuttle vector which can transfer large (>100 kb)
      human genomic DNA inserts back and forth between bacteria and human cells and
      which can be tracked in rapidly dividing human cells using a live cell assay. The
      vector (p5170) is based on the F factor-derived bacterial artificial chromosome
      cloning vector used in Escherichia coli, with the addition of the family of
      repeats element from the Epstein-Barr virus (EBV) latent origin of replication.
      This element provides nuclear retention in cells expressing the EBV protein EBNA
      1. We have subcloned a series of genomic DNA inserts into p5170 and transfected
      the constructs into an EBNA-1(+) human cell line. Episomal mitotic stability was
      quantitatively analysed using flow cytometry. The episomes were also tracked by
      time course photography of expanding colonies. A 117 kb episome was retained at
      approximately 2 copies/cell and could be shuttled unrearranged from the human
      cells into bacterial cells after 15 months of continuous cell growth.
      Furthermore, the episome could still be rescued from human cells cultured in the
      absence of selection for 198 days. Such a trackable E.coli /human cell line
      shuttle vector system capable of carrying >100 kb of genomic DNA in human cells
      could prove a valuable tool in gene expression studies.

PMID- 10076000
TI  - The presence of pseudouridine in the anticodon alters the genetic code: a
      possible mechanism for assignment of the AAA lysine codon as asparagine in
      echinoderm mitochondria.
AB  - It has been inferred from DNA sequence analyses that in echinoderm mitochondria
      not only the usual asparagine codons AAU and AAC, but also the usual lysine codon
      AAA, are translated as asparagine by a single mitochondrial (mt) tRNAAsn with the
      anticodon GUU. Nucleotide sequencing of starfish mt tRNAAsn revealed that the
      anticodon is GPsiU, U35 at the anticodon second position being modified to
      pseudouridine (Psi). In contrast, mt tRNALys, corresponding to another lysine
      codon, AAG, has the anticodon CUU. mt tRNAs possessing anti-codons closely
      related to that of tRNAAsn, but responsible for decoding only two codons each
      tRNAHis, tRNAAsp and tRNATyr-were found to possess unmodified U35 in all cases,
      suggesting the importance of Psi35 for decoding the three codons. Therefore, the
      decoding capabilities of two synthetic Escherichia coli tRNAAla variants with the
      anticodon GPsiU or GUU were examined using an E.coli in vitro translation system.
      Both tRNAs could translate not only AAC and AAU with similar efficiency, but also
      AAA with an efficiency that was approximately 2-fold higher in the case of
      tRNAAlaGPsiU than tRNAAlaGUU. These findings imply that Psi35 of echinoderm mt
      tRNAAsn actually serves to decode the unusual asparagine codon AAA, resulting in
      the alteration of the genetic code in echinoderm mitochondria.

PMID- 10076001
TI  - Identification, cloning and expression of p25, an AT-rich DNA-binding protein
      from the extreme thermophile, Thermus aquaticus YT-1.
AB  - Although the G+C content of Thermus aquaticus YT-1 chromosomal DNA is 67.4%,
      regions with lower G+C content have also been observed. AT-rich DNA-binding
      proteins may contribute to the thermostability and biological functions of these
      DNA regions at Thermus growth temperatures. Using double-stranded DNA (dsDNA)
      cellulose chromatography, a T.aquaticus YT-1 protein, designated as p25, was
      identified to bind preferentially to AT-rich DNA. The gene encoding p25 was
      cloned and sequenced after immunoscreening T.aquaticus YT-1 expression libraries.
      The deduced primary structure of p25 is 211 amino acids in length with a
      molecular weight of 23 225 Da. Native p25 was purified and characterized as a
      homodimer with modification possibly at lysine and arginine residues. Its
      preferential and temperature-dependent binding to AT-rich DNA was confirmed with
      mobility-shift DNA-binding assays. The protein was demonstrated to bind
      preferentially to dsDNA instead of single-stranded DNA. The binding of p25 to
      dsDNA also improved the thermotolerence of this protein. Overexpression study of
      fusion p25 suggested that the N-terminus of the protein might form the DNA
      binding domain or be closely involved in DNA-binding activity.

PMID- 10076002
TI  - Design, characterization and testing of tRNA3Lys-based hammerhead ribozymes.
AB  - A hammerhead ribozyme targeted against the HIV-1 env coding region was expressed
      as part of the anticodon loop of human tRNA3Lys without sacrificing tRNA
      stability or ribozyme catalytic activity. These tRNA-ribozymes were isolated from
      a library which was designed to contain linkers (sequences connecting the
      ribozyme to the anticodon loop) of random sequence and variable length. The
      ribozyme target site was provided in cis during selection and in trans during
      subsequent characterization. tRNA-ribozymes that possessed ideal combinations of
      linkers were expected to recognize the cis target site more freely and undergo
      cleavage. The cleaved molecules were isolated, cloned and characterized. Active
      tRNA-ribozymes were identified and the structural features conducive to cleavage
      were defined. The selected tRNA-ribozymes were stable, possessed cleavage rates
      lower or similar to the linear hammerhead ribozyme, and could be transcribed by
      an extract containing RNA polymerase III. Retroviral vectors expressing tRNA
      ribozymes were tested in a human CD4+ T cell line and were shown to inhibit HIV-1
      replication. These tRNA3Lys-based hammerhead ribozymes should therefore prove to
      be valuable for both basic and applied research. Special application is sought in
      HIV-1 or HIV-2 gene therapy.

PMID- 10076003
TI  - Plant cell-directed control of virion sense gene expression in wheat dwarf virus.
AB  - We have used particle bombardment (biolistics) to deliver replication-competent
      wheat dwarf virus (WDV)-based constructs, carrying reporter gene sequences fused
      to the virion sense promoter (Pv) or the CaMV 35S promoter, to suspension culture
      cells and immature zygotic embryos of wheat. While the replication of WDV double
      stranded DNA forms (replicons) was equivalent between wheat suspension culture
      cells and embryos, GUS reporter gene activity was 20-40 times higher in the
      embryo cultures. Maximum expression of WDV replicons occurred in the embryonic
      axis tissue of wheat embryos but their expression in suspension cells was
      compromised, compared with transiently maintained input plasmid DNA containing
      the same sequences. From these studies, we propose that WDV replicons are subject
      to a host cell-controlled competency for virion sense transcription. The term
      competency is used to distinguish between the phenomenon described here and
      control of gene expression by specific transcription factors. Control of
      competency is independent of Pv, the replacement 35S promoter and of the
      complementary sense control of virion sense expression involving specific
      sequences in Pv. We propose that factors controlling the competency for replicon
      expression may be present in cells which, as well as maintaining high rates of
      DNA synthesis, are totipotent. Cell type control of active chromatin, methylation
      of specific sequences in WDV minichromosomes and/or interaction of virus-encoded
      proteins with specific host factors are considered as possible mechanisms.

PMID- 10076004
TI  - DNA hybridization on microparticles: determining capture-probe density and
      equilibrium dissociation constants.
AB  - Many DNA-probe assays utilize oligonucleotide-coated microparticles for capture
      of complementary nucleic acids from solution. During development of these assays,
      as well as in other particle-based nucleic acid applications, it is useful to
      know both the amount of duplex formation expected under various experimental
      conditions and the coating density of the capture oligonucleotide on the particle
      surface. We examined the simplest form of a DNA-probe microparticle assay:
      hybridization of a particle-bound capture oligonucleotide to its solution-phase
      complement. Fluorescein-labeled solution-phase oligonucleotide was hybridized to
      varying amounts of particles, and the amount of labeled oligonucleotide remaining
      in solution at equilibrium was measured. We present a simple two-state, all-or
      none model for bimolecular hybridization of non-self-complementary sequences that
      can be used to calculate the equilibrium dissociation constant ( Kd ) from
      hybridization data. With experimental conditions where both the Kd value and the
      concentration of capture probe in the reaction are small relative to the
      concentration of labeled complementary oligonucleotide in the reaction, density
      of the capture probe on the particle's surface can also be determined. Kd values
      for particle-based hybridization were different from those obtained from solution
      phase thermodynamic parameters. At higher temperatures, hybridization on
      particles was more efficient than hybridization in solution.

PMID- 10076005
TI  - Crystal structure of a 14 bp RNA duplex with non-symmetrical tandem GxU wobble
      base pairs.
AB  - Adjacent GxU wobble base pairs are frequently found in rRNA. Atomic structures of
      small RNA motifs help to provide a better understanding of the effects of various
      tandem mismatches on duplex structure and stability, thereby providing better
      rules for RNA structure prediction and validation. The crystal structure of an
      RNA duplex containing the sequence r(GGUAUUGC-GGUACC)2 has been solved at 2.1 A
      resolution using experimental phases. Novel refinement strategies were needed for
      building the correct solvent model. At present, this is the only short RNA duplex
      structure containing 5'-U-U-3'/3'-G-G-5' non-symmetric tandem GxU wobble base
      pairs. In the 14mer duplex, the six central base pairs are all displaced away
      from the helix axis, yielding significant changes in local backbone conformation,
      helix parameters and charge distribution that may provide specific recognition
      sites for biologically relevant ligand binding. The greatest deviations from A
      form helix occur where the guanine of a wobble base pair stacks over a purine
      from the opposite strand. In this vicinity, the intra-strand phosphate distances
      increase significantly, and the major groove width increases up to 3 A.
      Structural comparisons with other short duplexes containing symmetrical tandem
      GxU or GxT wobble base pairs show that nearest-neighbor sequence dependencies
      govern helical twist and the occurrence of cross-strand purine stacks.

PMID- 10076006
TI  - Identification of a novel transcriptional activity of mammalian Id proteins.
AB  - The Id proteins are a family of related mammalian helix-loop-helix (HLH) proteins
      which can interact with other HLH proteins but lack a basic region and are thus
      not thought to bind to DNA. Instead, they are hypothesized to act as dominant
      negative regulators of DNA-binding basic HLH (bHLH) proteins, by forming inactive
      heterodimers with these proteins. All four Id family proteins possess related HLH
      dimerization domains and can interact with similar bHLH proteins, although with
      differing affinities. The functions of the largely unrelated N- and C-terminal
      regions of the proteins are unknown. In this study, we have identified a novel
      transcriptional activity of the mammalian Id proteins. We show that when fused to
      the heterologous GAL4 DNA-binding domain, all four of the mammalian Id proteins
      can activate GAL4-dependent transcription. The HLH domain is necessary for the
      transactivation activity observed, suggesting that interaction with a cellular
      HLH protein is required. Co-transfection with exogenous Class A bHLH proteins (E
      proteins) greatly potentiates the transactivation, which is abolished upon co
      transfection with Class B bHLH proteins. These results are consistent with the
      idea that the Id proteins have a transcriptional activity when present in a DNA
      binding complex.

PMID- 10076007
TI  - The mouse Y-box protein, MSY2, is associated with a kinase on non-polysomal mouse
      testicular mRNAs.
AB  - In male germ cells many mRNAs are sequestered by proteins into translationally
      silent messenger ribo-nucleoprotein (mRNP) particles. These masked paternal mRNAs
      are stored and translated at specific times of germ cell development. Little is
      known about the mammalian testicular mRNA masking proteins bound to non-polysomal
      mRNAs. In this report, the major proteins binding to non-polysomal testicular
      mRNAs were isolated and analyzed. The two predominant proteins identified were: a
      Y-box protein (MSY2), the mammalian homolog to the Xenopus oocyte masking protein
      FRGY2/mRNP3+4, and a poly(A) binding protein. A kinase activity was also found
      associated with these non-polysomal RNAs. The kinase co-immunoprecipitates with
      MSY2 and phosphorylates MSY2 in vitro. The MSY2 associated kinase is not casein
      kinase 2, the kinase believed to phosphorylate mRNP3+4 in oocytes, but a yet
      unidentified kinase. MSY2 was found to be phosphorylated in vivo and MSY2
      dephosphorylation led to a decrease in its affinity to bind RNA as judged by
      northwestern blotting. Therefore, testicular masked mRNAs may be regulated by the
      phosphorylation state of MSY2. Reconstitution experiments in which non-polysomal
      mRNA-binding proteins are dissociated from their RNAs and allowed to bind to
      exogenous mRNAs suggest that MSY2 binds RNA in a sequence-independent fashion.
      Furthermore, association of the non-polysomal derived proteins to exogenous non
      specific mRNAs led to their translational repression in vitro.

PMID- 10076008
TI  - Molecular gene organisation and secondary structure of the mitochondrial large
      subunit ribosomal RNA from the cultivated Basidiomycota Agrocybe aegerita: a 13
      kb gene possessing six unusual nucleotide extensions and eight introns.
AB  - The complete gene sequence and secondary structure of the mitochondrial LSU rRNA
      from the cultivated Basidiomycota Agrocybe aegerita was derived by chromosome
      walking. The A.aegerita LSU rRNA gene (13 526 nt) represents, to date, the
      longest described, due to the highest number of introns (eight) and the
      occurrence of six long nucleotidic extensions. Seven introns belong to group I,
      while the intronic sequence i5 constitutes the first typical group II intron
      reported in a fungal mitochondrial LSU rDNA. As with most fungal LSU rDNA introns
      reported to date, four introns (i5-i8) are distributed in domain V associated
      with the peptidyl-transferase activity. One intron (i1) is located in domain I,
      and three (i2-i4) in domain II. The introns i2-i8 possess homologies with other
      fungal, algal or protozoan introns located at the same position in LSU rDNAs. One
      of them (i6) is located at the same insertion site as most Ascomycota or algae
      LSU introns, suggesting a possible inheritance from a common ancestor. On the
      contrary, intron i1 is located at a so-far unreported insertion site. Among the
      six unusual nucleotide extensions, five are located in domain I and one in domain
      V. This is the first report of a mitochondrial LSU rRNA gene sequence and
      secondary structure for the whole Basidiomycota division.

PMID- 10076009
TI  - An improved method for routine preparation of intact artificial chromosome DNA
      (340-1000 kb) for transfection into human cells.
AB  - The transfer of high molecular weight (HMW) DNA into mammalian cells is an
      important strategy for assessing human gene expression and chromosome structure
      and function. However, using current methods, it is difficult to dependably
      prepare intact HMW DNA because of the susceptibility of the DNA to degradation
      and physical shearing. Here we describe a strategy whereby intact artificial
      chromosome DNA (as large as 1 Mb) can be routinely prepared from yeast. Strict
      adherence to this protocol has resulted in: (i) >90% of liquid DNA preparations
      containing largely intact DNA; (ii) transfection efficiencies for the development
      of stable human clonal cell lines ranging from 5 x 10(-7) to 8.8 x 10(-5); and
      (iii) the presence of markers from both YAC arms in 30-42% of the human
      fibrosarcoma cell HT1080 clones and 100% of the CF lung epithelial cell lines IB3
      1 and CFT1 clones, suggesting that the HMW DNA is potentially intact in a
      substantial proportion of clones. Using this protocol for DNA preparation,
      successful transfection of functional 1 Mb human artificial chromosome DNA into
      human cells has also been achieved. This methodology should prove useful to those
      interested in using HMW human DNA for gene expression and functional analysis or
      for linear artificial chromosome construction, since integrity is absolutely
      critical for the success of these studies.

PMID- 10076010
TI  - Photosystem II of green plants: on the possible role of retarded protonic
      relaxation in water oxidation1 
AB  - Photosystem II (PSII) of green plants and cyanobacteria uses energy of light to
      oxidize water and to produce oxygen. The available estimates of the oxidizing
      potential of P680+, the primary donor of PSII, yield value of about 1.15 V. Two
      main factors are suggested to add up and engender this high oxidizing potential,
      namely: (1) the electrostatic influence dominated by Arg-181 of the D2 subunit
      which elevates the oxidizing potential of P680+ up to 1 V, some 0.1 V above the
      Em value of a hydrogen-bonded chlorophyll a; and (2) the dynamic component of
      0.10-0.15 V due to the experimentally demonstrated retarded protonic relaxation
      at the P680 site.

PMID- 10076011
TI  - Structural features and assembly of the soluble overexpressed PsaD subunit of
      photosystem I.
AB  - PsaD is a peripheral protein on the reducing side of photosystem I (PS I). We
      expressed the psaD gene from the thermophilic cyanobacterium Mastigocladus
      laminosus in Escherichia coli and obtained a soluble protein with a polyhistidine
      tag at the carboxyl terminus. The soluble PsaD protein was purified by Ni
      affinity chromatography and had a mass of 16716 Da by MALDI-TOF. The N-terminal
      amino acid sequence of the overexpressed PsaD matched the N-terminal sequence of
      the native PsaD from M. laminosus. The soluble PsaD could assemble into the PsaD
      less PS I. As determined by isothermal titration calorimetry, PsaD bound to PS I
      with 1.0 binding site per PS I, the binding constant of 7.7x10(6) M-1, and the
      enthalpy change of -93.6 kJ mol-1. This is the first time that the binding
      constant and binding heat have been determined in the assembly of any
      photosynthetic membrane protein. To identify the surface-exposed domains,
      purified PS I complexes and overexpressed PsaD were treated with N
      hydroxysuccinimidobiotin (NHS-biotin) and biotin-maleimide, and the biotinylated
      residues were mapped. The Cys66, Lys21, Arg118 and Arg119 residues were exposed
      on the surface of soluble PsaD whereas the Lys129 and Lys131 residues were not
      exposed on the surface. Consistent with the X-ray crystallographic studies on PS
      I, circular dichroism spectroscopy revealed that PsaD contains a small proportion
      of alpha-helical conformation.

PMID- 10076012
TI  - Interaction of photosynthetic pigments with various organic solvents. Magnetic
      circular dichroism approach and application to chlorosomes 
AB  - Magnetic circular dichroism (MCD) and absorption spectra have been measured on
      three intact photosynthetic pigments with the chlorin ring as macrocycle:
      chlorophyll a, bacteriochlorophyll c and d, in various hydrophilic organic
      solvents. The MCD intensity of a Qy(0-0) transition for the Mg chlorin derivative
      was sensitive to the coordination state of the central Mg atom by the solvent
      molecules. The coordination number has been characterized in terms of the
      relationship between the ratio of Qy(0-0) MCD intensity to its dipole strength
      (B/D) and the difference in energies of Qx(0-0) and Qy(0-0) transitions. This
      relationship depends not only on the coordination number of the magnesium (Mg)
      atom but also on the coordination interaction of the solvent molecules to the Mg
      atom, and can clarify the spectroscopic change of chlorosomes by alcohol
      treatment. We propose that the correlation between the MCD intensity of Qy(0-0)
      transition and the energy difference can be used as a new measure for determining
      the coordination number of the Mg atom and for estimating the interaction
      strength of the Mg atom with solvent molecules.

PMID- 10076013
TI  - Sequence analysis of cytochrome bd oxidase suggests a revised topology for
      subunit I.
AB  - Numerous sequences of the cytochrome bd quinol oxidase (cytochrome bd) have
      recently become available for analysis. The analysis has revealed a small number
      of conserved residues, a new topology for subunit I and a phylogenetic tree
      involving extensive horizontal gene transfer. There are 20 conserved residues in
      subunit I and two in subunit II. Algorithms utilizing multiple sequence
      alignments predicted a revised topology for cytochrome bd, adding two
      transmembrane helices to subunit I to the seven that were previously indicated by
      the analysis of the sequence of the oxidase from E. coli. This revised topology
      has the effect of relocating the N-terminus and C-terminus to the periplasmic and
      cytoplasmic sides of the membrane, respectively. The new topology repositions I
      H19, the putative ligand for heme b595, close to the periplasmic edge of the
      membrane, which suggests that the heme b595/heme d active site of the oxidase is
      located near the outer (periplasmic) surface of the membrane. The most highly
      conserved region of the sequence of subunit I contains the sequence GRQPW and is
      located in a predicted periplasmic loop connecting the eighth and ninth
      transmembrane helices. The potential importance of this region of the protein was
      previously unsuspected, and it may participate in the binding of either quinol or
      heme d. There are two very highly conserved glutamates in subunit I, E99 and
      E107, within the third transmembrane helix (E. coli cytochrome bd-I numbering).
      It is speculated that these glutamates may be part of a proton channel leading
      from the cytoplasmic side of the membrane to the heme d oxygen-reactive site, now
      placed near the periplasmic surface. The revised topology and newly revealed
      conserved residues provide a clear basis for further experimental tests of these
      hypotheses. Phylogenetic analysis of the new sequences of cytochrome bd reveals
      considerable deviation from the 16sRNA tree, suggesting that a large amount of
      horizontal gene transfer has occurred in the evolution of cytochrome bd.

PMID- 10076014
TI  - On the role of high-potential iron-sulfur proteins and cytochromes in the
      respiratory chain of two facultative phototrophs 
AB  - The capability of high potential iron-sulfur proteins (HiPIPs) and soluble
      cytochromes to shuttle electrons between the bc1 complex and the terminal oxidase
      in aerobically grown cells of Rhodoferax fermentans and Rhodospirillum salinarum,
      two facultative phototrophs, was evaluated. In Rs. salinarum, HiPIP and a c-type
      cytochrome (alpha-band at 550 nm, Em,7=+290 mV) are both involved in the electron
      transfer step from the bc1 complex to the terminal oxidase. Kinetic studies
      indicate that cytochrome c550 is more efficient than HiPIP in oxidizing the bc1
      complex, and that HiPIP is a more efficient reductant of the terminal oxidase as
      compared to cytochrome c550. Rs. salinarum cells contain an additional c-type
      cytochrome (asymmetric alpha-band at 556 nm, Em,7=+180 mV) which is able to
      reduce the terminal oxidase, but unable to oxidize the bc1 complex. c-type
      cytochromes could not be isolated from Rf. fermentans, in which HiPIP, the most
      abundant soluble electron carrier, is reduced by the bc1 complex (zero-order
      kinetics) and oxidized by the terminal oxidase (first-order kinetics),
      respectively. These data, taken together, indicate for the first time that HiPIPs
      play a significant role in bacterial respiratory electron transfer.

PMID- 10076015
TI  - Characterization of a novel unconjugated pteridine glycoside, cyanopterin, in
      Synechocystis sp. PCC 6803.
AB  - A new pteridine glycoside, called cyanopterin, was isolated from Synechocystis
      sp. PCC 6803 and its structure was elucidated as 6-[1-(4-O-methyl-(alpha-d
      glucuronyl)-(1, 6)-(beta-d-galactosyloxy]methylpterin by chemical degradation and
      1H- and 13C-NMR spectroscopic means. Cyanopterin is constitutively synthesized at
      a relatively high intracellular concentration that is comparable to that of
      chlorophyll a in a molar ratio of approximately 1 to 1.6. The in vivo oxidation
      state of cyanopterin is primarily the fully reduced 5,6,7,8-tetrahydro form. The
      cellular function is unknown at present. The findings have established a model
      system, using Synechocystis sp. PCC 6803, for studies of the physiological
      functions of unconjugated pteridine glycosides found mostly in cyanobacteria.

PMID- 10076016
TI  - Evaluation of relative contributions of two enzymes supposed to metabolise
      hydrogen peroxide in Paracoccus denitrificans.
AB  - A biosensor exploiting an electrochemically mediated enzyme-catalysed reaction
      was used to quantify relative contributions of cytoplasmic catalase and
      periplasmic cytochrome c peroxidase to the overall rate of hydrogen peroxide
      breakdown in cells of Paracoccus denitrificans. The effects of antimycin (an
      inhibitor of electron flow to cytochrome c peroxidase), the reaction rate versus
      substrate concentration profiles for the whole cells and subcellular fractions,
      and the time courses of oxygen concentration demonstrated a profound decrease in
      the capacity of cytochrome c peroxidase to reduce H2O2 under in vivo conditions.
      The reason is suggested to be a competition for available electrons between the
      enzyme and terminal oxidases metabolising oxygen produced by catalase.

PMID- 10076017
TI  - Visualization of cyclosporin A and Ca2+-sensitive cyclical mitochondrial
      depolarizations in cell culture.
AB  - Mitochondria not only facilitate chemiosmotic energy transduction, but also are
      excitable organelles that are important participants in intracellular Ca2+
      signaling and are obligate participants in the active cell death cascade known as
      apoptosis. Underlying these functions is the cyclosporin A (CSA)-sensitive
      mitochondrial permeability transition pore (MTP), which can open transiently in a
      low conductance mode (MTPL) to relieve excess Ca2+, and irreversibly during the
      initiation of apoptosis. Here we image for the first time CSA- and Ca2+-sensitive
      cyclical mitochondrial depolarizations in cultures of the SH-SY5Y human
      neuroblastoma cell. In addition, we show that mitochondrial transmembrane
      potential (DeltaPsi) increases in response to CSA, indicating a baseline channel
      activity. Moreover, networks of mitochondria are shown to behave as an excitable
      system that may use Ca2+ as a diffusible messenger to recruit neighboring
      mitochondria to depolarize. We propose that these depolarizations represent MTPL
      activity. Our data further reinforce the notion that mitochondria are excitable
      organelles and suggest coordinated activation of MTPL.

PMID- 10076018
TI  - Dependence of yeast mitochondrial unselective channel activity on the respiratory
      chain.
AB  - The dependence of yeast mitochondrial unselective channel activity on the
      respiratory chain was investigated. Modulation of the respiratory chain with
      different substrates and inhibitors showed that channel activity was dependent on
      the electron flow rate through the chain and that external NADH only could
      provide a sufficient rate to activate the channel. These results support the
      hypothesis that the yeast mitochondrial unselective channel may be involved in
      the oxidation of cytosolic NADH without coupling to ATP synthesis.

PMID- 10076019
TI  - Regulation of mitochondrial KATP channel by redox agents.
AB  - The ATP-dependent K+ channel (KATP) was purified from the inner mitochondrial
      membrane and reconstituted into lipid bilayer membranes. KATP activity was
      inhibited by high concentrations of ATP and ADP, but activated by low
      concentrations (up to 200 microM) of ADP. p-Diethylaminoethylbenzoate (DEB) acted
      as a KATP opener: at micromolar concentrations, it reversed inhibition by ATP and
      ADP and it also prevented KATP rundown. Pelargonidine, extracted from flowers of
      Pelargonium, reduced spontaneous activity of KATP channels and diminished their
      potentiation by DEB. Their opposite action on KATP corresponded with their
      opposite redox properties in reactions with free radicals: DEB behaved as an
      electron donor, whereas pelargonidine acted as an electron acceptor. We
      hypothesize that thiol groups on mitoKATP are targets for redox-active ligans.

PMID- 10076020
TI  - Light-harvesting antenna function of phycoerythrin in prochlorococcus marinus 
AB  - Prochlorococcus marinus strain CCMP 1375 is the sole prokaryote to possess
      phycoerythrin in addition to (divinyl-)chlorophyll a/b binding antenna complexes.
      Here we demonstrate, employing a spectrofluorimetric assay, that phycoerythrin
      serves a light-harvesting antenna function (transfers energy to chlorophylls).

PMID- 10076021
TI  - The mitochondrial genome: structure, transcription, translation and replication.
AB  - Mitochondria play a central role in cellular energy provision. The organelles
      contain their own genome with a modified genetic code. The mammalian
      mitochondrial genome is transmitted exclusively through the female germ line. The
      human mitochondrial DNA (mtDNA) is a double-stranded, circular molecule of 16569
      bp and contains 37 genes coding for two rRNAs, 22 tRNAs and 13 polypeptides. The
      mtDNA-encoded polypeptides are all subunits of enzyme complexes of the oxidative
      phosphorylation system. Mitochondria are not self-supporting entities but rely
      heavily for their functions on imported nuclear gene products. The basic
      mechanisms of mitochondrial gene expression have been solved. Cis-acting mtDNA
      sequences have been characterised by sequence comparisons, mapping studies and
      mutation analysis both in vitro and in patients harbouring mtDNA mutations.
      Characterisation of trans-acting factors has proven more difficult but several
      key enzymes involved in mtDNA replication, transcription and protein synthesis
      have now been biochemically identified and some have been cloned. These studies
      revealed that, although some factors may have an additional function elsewhere in
      the cell, most are unique to mitochondria. It is expected that cell cultures of
      patients with mitochondrial diseases will increasingly be used to address
      fundamental questions about mtDNA expression.

PMID- 10076022
TI  - Mitochondrial encephalomyopathies: the enigma of genotype versus phenotype.
AB  - Over the past decade a large body of evidence has accumulated implicating defects
      of human mitochondrial DNA in the pathogenesis of a group of disorders known
      collectively as the mitochondrial encephalomyopathies. Although impaired
      oxidative phosphorylation is likely to represent the final common pathway leading
      to cellular dysfunction in these diseases, fundamental issues still remain
      elusive. Perhaps the most challenging of these is to understand the mechanisms
      which underlie the complex relationship between genotype and phenotype. Here we
      examine this relationship and discuss some of the factors which are likely to be
      involved.

PMID- 10076023
TI  - Clinical, biochemical and molecular genetic features of Leber's hereditary optic
      neuropathy.
AB  - Leber's hereditary optic neuropathy (LHON) has traditionally been considered a
      disease causing severe and permanent visual loss in young adult males. In nearly
      all families with LHON it is associated with one of three pathogenic
      mitochondrial DNA (mtDNA) mutations, at bp 11778, 3460 or 14484. The availability
      of mtDNA confirmation of a diagnosis of LHON has demonstrated that LHON occurs
      with a wider range of age at onset and more commonly in females than previously
      recognised. In addition, analysis of patients grouped according to mtDNA mutation
      has demonstrated differences both in the clinical features of visual failure and
      in recurrence risks to relatives associated with each of the pathogenic mtDNA
      mutations. Whilst pathogenic mtDNA mutations are required for the development of
      LHON, other factors must be reponsible for the variable penetrance and male
      predominance of this condition. Available data on a number of hypotheses
      including the role of an additional X-linked visual loss susceptibility locus,
      impaired mitochondrial respiratory chain activity, mtDNA heteroplasmy,
      environmental factors and autoimmunity are discussed. Subacute visual failure is
      seen in association with all three pathogenic LHON mutations. However, the
      clinical and experimental data reviewed suggest differences in the phenotype
      associated with each of the three mutations which may reflect variation in the
      disease mechanisms resulting in this common end-point.

PMID- 10076024
TI  - Mitochondrial involvement in Parkinson's disease, Huntington's disease,
      hereditary spastic paraplegia and Friedreich's ataxia.
AB  - Respiratory chain dysfunction has been identified in several neurodegenerative
      disorders. In Friedreich's ataxia (FA) and Huntington's disease (HD), where the
      respective mutations are in nuclear genes encoding non-respiratory chain
      mitochondrial proteins, the defects in oxidative phosphorylation are clearly
      secondary. In Parkinson's disease (PD) the situation is less clear, with some
      evidence for a primary role of mitochondrial DNA in at least a proportion of
      patients. The pattern of the respiratory chain defect may provide some clue to
      its cause; in PD there appears to be a selective complex I deficiency; in HD and
      FA the deficiencies are most severe in complex II/III with a less severe defect
      in complex IV. Aconitase activity in HD and FA is severely decreased in brain and
      muscle, respectively, but appears to be normal in PD brain. Free radical
      generation is thought to be of importance in both HD and FA, via excitotoxicity
      in HD and abnormal iron handling in FA. The oxidative damage observed in PD may
      be secondary to the mitochondrial defect. Whatever the cause(s) and sequence of
      events, respiratory chain deficiencies appear to play an important role in the
      pathogenesis of neurodegeneration. The mitochondrial abnormalities induced may
      converge on the function of the mitochondrion in apoptosis. This mode of cell
      death is thought to play an important role in neurodegenerative diseases and it
      is tempting to speculate that the observed mitochondrial defects in PD, HD and FA
      result directly in apoptotic cell death, or in the lowering of a cell's threshold
      to undergo apoptosis. Clarifying the role of mitochondria in pathogenesis may
      provide opportunities for the development of treatments designed to reverse or
      prevent neurodegeneration.

PMID- 10076025
TI  - Mitochondrial involvement in Alzheimer's disease.
AB  - The causes of most neurodegenerative diseases, including sporadic Alzheimer's
      disease (AD), remain enigmatic. There is, however, increasing evidence
      implicating mitochondrial dysfunction resulting from deafferentiation of
      disconnected neural circuits in the pathogenesis of energy deficit in AD. The
      patterns of reduced expression of both mitochondrial DNA (mtDNA) and nuclear DNA
      (nDNA) encoded genes is consistent with a physiological down-regulation of the
      mitochondrial respiratory chain in response to reduced neuronal activity. On the
      other hand, the role(s) of somatic cell or maternally inherited mtDNA mutations
      in the pathogenesis of mitochondrial dysfunction in AD are still controversial.

PMID- 10076026
TI  - Mitochondria in organismal aging and degeneration.
AB  - Several lines of experimentation support the view that the genetic, biochemical
      and bioenergetic functions of somatic mitochondria deteriorate during normal
      aging. Deletion mutations of the mitochondrial genome accumulate exponentially
      with age in nerve and muscle tissue of humans and multiple other species. In
      muscle, a tissue that undergoes age-related fiber loss and atrophy in humans,
      there is an exponential rise in the number of cytochrome-oxidase-deficient
      fibers, which is first detectable in the fourth decile of age. Most biochemical
      studies of animal mitochondrial activity indicate a decline in electron transport
      activity with age, as well as decreased bioenergetic capacity with age, as
      measured by mitochondrial membrane potential. Mitochondrial mutations may be both
      the result of mitochondrial oxidative stress, and cells bearing pure populations
      of pathogenic mitochondrial mutations are sensitized to oxidant stress. Oxidant
      stress to mitochondria is known to induce the mitochondrial permeability
      transition, which has recently been implicated in the release of cytochrome c and
      the initiation of apoptosis. Thus several lines of evidence support a
      contribution of mitochondrial dysfunction to the phenotypic changes associated
      with aging.

PMID- 10076027
TI  - Apoptosis in neurodegenerative diseases: the role of mitochondria.
AB  - Nerve cell death is the central feature of the human neurodegenerative diseases.
      It has long been thought that nerve cell death in these disorders occurs by way
      of necrosis, a process characterized by massive transmembrane ion currents,
      compromise of mitochondrial ATP production, and the formation of high levels of
      reactive oxygen species combining to induce rapid disruption of organelles, cell
      swelling, and plasma membrane rupture with a secondary inflammatory response.
      Nuclear DNA is relatively preserved. Recent evidence now indicates that the
      process of apoptosis rather than necrosis primarily contributes to nerve cell
      death in neurodegeneration. This has opened up new avenues for understanding the
      pathogenesis of neurodegeneration and may lead to new and more effective
      therapeutic approaches to these diseases.

PMID- 10076028
TI  - Nitric oxide, mitochondria and neurological disease.
AB  - Damage to the mitochondrial electron transport chain has been suggested to be an
      important factor in the pathogenesis of a range of neurological disorders, such
      as Parkinson's disease, Alzheimer's disease, multiple sclerosis, stroke and
      amyotrophic lateral sclerosis. There is also a growing body of evidence to
      implicate excessive or inappropriate generation of nitric oxide (NO) in these
      disorders. It is now well documented that NO and its toxic metabolite,
      peroxynitrite (ONOO-), can inhibit components of the mitochondrial respiratory
      chain leading, if damage is severe enough, to a cellular energy deficiency state.
      Within the brain, the susceptibility of different brain cell types to NO and ONOO
      exposure may be dependent on factors such as the intracellular reduced
      glutathione (GSH) concentration and an ability to increase glycolytic flux in the
      face of mitochondrial damage. Thus neurones, in contrast to astrocytes, appear
      particularly vulnerable to the action of these molecules. Following cytokine
      exposure, astrocytes can increase NO generation, due to de novo synthesis of the
      inducible form of nitric oxide synthase (NOS). Whilst the NO/ONOO- so formed may
      not affect astrocyte survival, these molecules may diffuse out to cause
      mitochondrial damage, and possibly cell death, to other cells, such as neurones,
      in close proximity. Evidence is now available to support this scenario for
      neurological disorders, such as multiple sclerosis. In other conditions, such as
      ischaemia, increased availability of glutamate may lead to an activation of a
      calcium-dependent nitric oxide synthase associated with neurones. Such
      increased/inappropriate NO formation may contribute to energy depletion and
      neuronal cell death. The evidence available for NO/ONOO--mediated mitochondrial
      damage in various neurological disorders is considered and potential therapeutic
      strategies are proposed.

PMID- 10076029
TI  - A novel small protein associated with a conjugated trienoic chromophore from
      membranes of scallop adductor muscle: phosphorylation by protein kinase A.
AB  - Membranes enriched in sarcolemma from the cross-striated adductor muscle of the
      deep sea scallop have been found to contain a previously undescribed small
      protein of 6-8 kDa that can be released by treatment with organic solvent
      mixtures. This proteolipid co-purified with a non-amino acid chromophore
      containing a conjugated trienoic moiety. Although common in plants and algae,
      such a stable conjugated trienoic group is unusual for an animal cell. The N
      terminal amino acid sequence of the protein was XEFQHGLFGXF/ADNIGLQ, which most
      strongly resembles sequences in the triacyl glycerol lipase precursor and the
      product of the human breast cancer susceptibility gene BRCA 1, but does not show
      similarity to previously described proteolipids. The protein was found to be one
      of the major substrates in its parent membrane for the catalytic subunit of
      protein kinase A, which may imply a regulatory function for this molecule.

PMID- 10076030
TI  - Non-selective voltage-activated cation channel in the human red blood cell
      membrane.
AB  - Using the patch-clamp technique, a non-selective voltage-activated Na+ and K+
      channel in the human red blood cell membrane was found. The channel operates only
      at positive membrane potentials from about +30 mV (inside positive) onwards. For
      sodium and potassium ions, similar conductances of about 21 pS were determined.
      Together with the recently described K+(Na+)/H+ exchanger, this channel is
      responsible for the increase of residual K+ and Na+ fluxes across the human red
      blood cell membrane when the cells are suspended in low ionic strength medium.

PMID- 10076031
TI  - Transcription of the adenine nucleotide translocase isoforms in various types of
      tissues in the rat.
AB  - Two different isoforms of the adenine nucleotide translocase (ANT1 and ANT2) have
      been identified in the rat. In order to obtain enhanced knowledge of the ANT
      isoform expression, we analyzed the transcription pattern of both isoforms and
      their mRNA levels in various tissues of the rat using the PCR technique. A
      predominant ANT1 mRNA percentage was recorded in the skeletal muscle, heart and
      brain, ranging from 81 to 58%. In contrast to these tissues, the percentages of
      ANT2 were dominant with a range from 59 to 75% in the kidney, lung, spleen and
      liver. The level of total ANT mRNA varied markedly in the various organs. Tissues
      with a dominant ANT1 percentage simultaneously showed a high level of total ANT
      transcription (24-41 attomol/ng total RNA). In comparison to the latter, tissues
      with a prevalent ANT2 transcription were shown to have an even lower ANT
      transcription level (2-5 attomol/ng total RNA). The predominance of the ANT1
      expression appeared to be restricted to tissues with an inability to regenerate
      by means of mitotic division, whereas a prevalent ANT2 transcription is found in
      cell types able to proliferate. The level of total ANT transcription but not the
      individual ANT isoform expression depends to a great extent on the energy
      requirements of the tissue.

PMID- 10076032
TI  - Properties of a new calcium-permeable single channel from tracheal microsomes.
AB  - After the incorporation of the tracheal microsomal membrane into bilayer lipid
      membrane (BLM), a new single channel permeable for calcium was observed. Using
      the BLM conditions, 53 mM Ca2+ in trans solution versus 200 nM Ca2+ in cis
      solution, the single calcium channel current at 0 mV was 1.4-2.1 pA and
      conductance was 62-75 pS. The channel Ca2+/K+ permeability ratio was 4.8. The
      open probability (P-open) was in the range of 0.7-0.97. The P-open, measured at 
      10 mV to +30 mV (trans-cis), was not voltage dependent. The channel was neither
      inhibited by 10-20 microM ruthenium red, a specific blocker of ryanodine calcium
      release channel, nor by 10-50 microM heparin, a specific blocker of IP3 receptor
      calcium release channel, and its activity was not influenced by addition of 0.1
      mM MgATP. We suggest that the observed new channel is permeable for calcium, and
      it is neither identical with the known type 1 or 2 ryanodine calcium release
      channel, nor type 1 or 2 IP3 receptor calcium release channel.

PMID- 10076033
TI  - Characterization of non-dominant lethal mutations in the yeast plasma membrane H+
      ATPase gene.
AB  - Site-directed mutants of yeast ATPase were previously studied after introduction
      of mutant alleles into a yeast strain where these alleles were constitutively
      expressed while the expression of the wild-type chromosomal ATPase gene was
      turned off. As a functional H+ pump is essential, strong selective pressure leads
      to the accumulation of revertants during growth of cells harboring variants with
      low activity. Thus, constitutive expression of the mutant gene can select
      phenotypes which reflect events such as gene conversion or reversion. We have
      therefore re-evaluated the phenotypes of non-dominant lethal alleles in an
      alternative set of conditional expression systems. We show that eight of 11
      previously described site-directed mutations behave as recessive lethal alleles.

PMID- 10076034
TI  - A transfection compound series based on a versatile Tris linkage.
AB  - The family of cationic lipid transfection reagents described here demonstrates a
      modular design that offers potential for the ready synthesis of a wide variety of
      molecular variants. The key feature of these new molecules is the use of Tris as
      a linker for joining the hydrophobic domain to a cationic head group. The
      molecular design offers the opportunity to conveniently synthesise compounds
      differing in charge, the number and nature of hydrophobic groups in the
      hydrophobic domain and the characteristics of the spacer between the cationic and
      hydrophobic moieties. We show that prototype reagents of this design can deliver
      reporter genes into cultured cells with efficiencies rivaling those of
      established cationic lipid transfection reagents. A feature of these reagents is
      that they are not dependent on formulation with a neutral lipid for activity.

PMID- 10076035
TI  - Membrane dielectric responses of human T-lymphocytes following mitogenic
      stimulation.
AB  - Human peripheral blood T-lymphocytes, normally resting at the G0 phase, were
      stimulated with phytohemagglutinin (PHA) and interleukin-2 (IL-2) to induce the
      cell division cycle. The cells were examined at 24-h intervals for up to 96 h by
      flow cytometry to determine cell cycle distributions and by electrorotation to
      determine dielectric properties. The average membrane specific capacitance was
      found to vary from 12 (+/-1.5) mF/m2 prior to stimulation to 10 (+/-1.5) and 16
      (+/-3.5) mF/m2 at 24 and 48 h after stimulation, respectively, and to remain
      unchanged up to 96 h after stimulation. Scanning electron microscopy studies of
      the cells revealed an increased complexity in cell membrane morphology following
      stimulation, suggesting that the observed change in the membrane capacitance was
      dominated by the alteration of cell surface structures. The average electrical
      conductivity of the cell interior decreased from approximately 1.1 S/m prior to
      stimulation to approximately 0.8 S/m at 24 h after stimulation and showed little
      change thereafter. The average dielectric permittivity of the cell interior
      remained almost unchanged throughout the course of the cell stimulation. The
      percentage of T-lymphocytes in the S and G2/M phases increased from approximately
      4% prior to stimulation to approximately 11 and approximately 34% at 24 and 48 h
      after stimulation, respectively. The large change in membrane specific
      capacitance between the 24 and 48 h time period coincided with the large
      alteration in the cell cycle distribution where the S and G2/M populations
      increased by approximately 23%. These data, together with an analysis of the
      variation of the membrane capacitance during the cell cycle based on the cell
      cycle-dependent membrane lipid accumulation, show that there is a correlation
      between membrane capacitance and cell cycle phases that reflects alterations in
      the cell plasma membrane.

PMID- 10076036
TI  - Stretch-independent activation of the mechanosensitive cation channel in oocytes
      of Xenopus laevis.
AB  - Oocytes of the South African clawed toad Xenopus laevis possess in their plasma
      membrane a so-called stretch-activated cation channel (SAC) which is activated by
      gently applying positive or negative pressure (stretch) to the membrane patch
      containing the channels. We show here that this mechanosensitive channel acted as
      a spontaneously opening, stretch-independent non-selective cation channel (NSCC)
      in more than half of the oocytes that we investigated. In 55% of cell-attached
      patches (total number of patches, 58) on 30 oocytes from several different
      donors, we found NSCC opening events. These currents were increased by elevating
      the membrane voltage or raising the temperature. NSCC and SAC currents shared
      some properties regarding the relative conductances of Na+>Li+>Ca2+, gating
      behaviour and amiloride sensitivity. Stretch-independent currents could be
      clearly distinguished from stretch induced SAC currents by their voltage and
      temperature dependence. Open events of NSCC increased strongly when temperature
      was raised from 21 to 27 degrees C. NSCC currents could be partly inhibited by
      high concentrations of extracellular Gd3+ and amiloride (100 and 500 microM,
      respectively). We further show exemplarily that NSCC can seriously hamper
      investigations when oocytes are used for the expression of foreign ion channels.
      In particular, NSCC complicated investigations on cation channels with small
      conductance as we demonstrate for a 4 pS epithelial Na+ channel (ENaC) from
      guinea pig distal colon. Our studies on NSCCs suggest the involvement of these
      channels in oocyte temperature response and ion transport regulation. From our
      results we suggest that NSCC and SAC currents are carried by one protein
      operating in different modes.

PMID- 10076037
TI  - Liposomes fuse with sperm cells and induce activation by delivery of impermeant
      agents.
AB  - Sperm cell activation is a critical step in fertilization. To directly
      investigate the cell signaling events leading to sperm activation it is necessary
      to deliver membrane impermeant agents into the cytoplasm. In this study, the use
      of liposomes as possible agent-loading vectors was examined using (1) the
      octadecylrhodamine B (R18) and NBD phosphatidylethanolamine (NBD DHPE)/rhodamine
      phosphatidylethanolamine (rhod DHPE) fusion assays in bulk samples, (2) membrane
      transfer of fluorescence from liposome membranes labeled with R18 and rhodamine
      tagged phosphatidylethanolamine (TRITC DHPE), and (3) lumenal transfer of
      impermeant calcium ions from liposomes to sperm cells, a process that stimulated
      sperm cell activation. Intermediate-sized unilamellar liposomes (98.17+/-15.34
      nm) were prepared by the detergent-removal technique using sodium cholate as the
      detergent and a phosphatidylcholine/phosphatidylethanolamine/cholesterol (2:1:1
      mole ratio) lipid composition. In the R18 fusion assays, self-quenching increased
      logarithmically with increasing concentrations of R18 in the liposome membranes;
      addition of unlabeled sperm to R18-labeled liposomes lead to a rapid release of
      self-quenching. In the NBD DHPE/rhod DHPE resonance energy transfer (RET) fusion
      assay, RET was rapidly reduced under similar conditions. In addition, individual
      sperm became fluorescent when TRITC DHPE-labeled liposomes were incubated with
      unlabeled sperm cells. Incubation of sperm cells with empty liposomes did not
      significantly affect sperm cell activation and did not alter cell morphology.
      However, incubation with Ca (10 mM)-loaded liposomes resulted in a time-dependent
      increase in sperm cell activation (7.5-fold over controls after 15 min). We
      conclude that liposomes can be used for direct loading of membrane-impermeant
      agents into sea squirt sperm cell cytoplasm, and that delivery occurs via fusion
      and content intermixing.

PMID- 10076038
TI  - Maximum solubility of cholesterol in phosphatidylcholine and
      phosphatidylethanolamine bilayers.
AB  - In any lipid bilayer membrane, there is an upper limit on the cholesterol
      concentration that can be accommodated within the bilayer structure; excess
      cholesterol will precipitate as crystals of pure cholesterol monohydrate. This
      cholesterol solubility limit is a well-defined quantity. It is a first-order
      phase boundary in the phospholipid/cholesterol phase diagram. There are many
      different solubility limits in the literature, but no clear picture has emerged
      that can unify the disparate results. We have studied the effects that different
      sample preparation methods can have on the apparent experimental solubility
      limit. We find that artifactual demixing of cholesterol can occur during
      conventional sample preparation and that this demixed cholesterol may produce
      artifactual cholesterol crystals. Therefore, phospholipid/cholesterol suspensions
      which are prepared by conventional methods may manifest variable, falsely low
      cholesterol solubility limits. We have developed two novel preparative methods
      which are specifically designed to prevent demixing during sample preparation.
      For detection of the cholesterol crystals, X-ray diffraction has proven to be
      quantitative and highly sensitive. Experiments based on these methods yield
      reproducible and precise cholesterol solubility limits: 66 mol% for
      phosphatidylcholine (PC) bilayers and 51 mol% for phosphatidylethanolamine (PE)
      bilayers. We present evidence that these are true, equilibrium values. In
      contrast to the dramatic headgroup effect (PC vs. PE), acyl chain variations had
      no effect on the cholesterol solubility limit in four different PC/cholesterol
      mixtures.

PMID- 10076039
TI  - Hydrocarbon chain packing and the effect of ethanol on the thermotropic phase
      behavior of mixed-chain phosphatidylglycerols.
AB  - Previous studies in this laboratory have delineated the relationship between the
      acyl chain asymmetry of mixed-chain phosphatidylcholines and the effect of
      ethanol concentration ([EtOH]) on their melting behavior (Li et al., Biophys J.,
      70 (1996) 2784-2794). This present investigation extends these findings to
      another phospholipid family by using high-resolution differential scanning
      calorimetry (DSC) to characterize the effect of ethanol concentration on the main
      phase transition temperature (Tm) of five molecular species of mixed-chain
      phosphatidylglycerol (PG). For C(14):C(18)PG, C(15):C(17)PG, C(16):C(16)PG, and
      C(17):C(15)PG, a biphasic profile in the Tm versus [EtOH] plot was observed, and
      the minimum in the plot for each PG occurred at 33, 15, 19, and 36 mg/ml,
      respectively. This biphasic behavior is typical of phospholipids whose acyl chain
      asymmetry is fairly small. For C(18):C(14)PG, only a linear decrease in the Tm
      was observed as a function of ethanol concentration; this effect is
      characteristic of highly asymmetric phospholipids. Our DSC results obtained with
      mixed-chain PG in the presence of ethanol demonstrate that the acyl chain
      asymmetry of the five lipids studied can be ranked as follows:
      C(15):C(17)PG<C(16):C(16)PG<C(14):C(18)PG<C(17):C(15)PG<C(18):C(14)PG ,
      confirming independent results from this laboratory that the overall acyl chain
      structure of PG in the hydrated gel phase is opposite to that detected in the
      single crystals. In fully hydrated bilayers, the acyl chain conformation of PG is
      most likely to be similar to that of phosphatidylcholine.

PMID- 10076040
TI  - Thermotropic phase behavior of mixed-chain phosphatidylglycerols: implications
      for acyl chain packing in fully hydrated bilayers.
AB  - In this communication we report the first systematic investigation of the
      thermodynamic properties of fully hydrated mixed-chain phosphatidylglycerols (PG)
      using high-resolution differential scanning calorimetry (DSC). The crystal
      structure of dimyristoylphosphatidylglycerol shows an acyl chain conformation
      that is nearly opposite to that of phosphatidylcholine (PC). In PC, the sn-1
      chain is straight while the sn-2 chain contains a bend; for PG, the sn-1 contains
      a bend while the sn-2 chain is in the all-trans conformation (R.H. Pearson, I.
      Pascher, The molecular structure of lecithin dihydrate, Nature, 281 (1978) 499
      501; I. Pascher, S. Sundell, K. Harlos, H. Eibl, Conformational and packing
      properties of membrane lipids: the crystal structure of sodium
      dimyristoylphosphatidylglycerol, Biochim. Biophys. Acta, 896 (1987) 77-88). If
      the structure of PG found in the single crystal can be extrapolated to that in
      the fully hydrated gel-state bilayer, the observed difference in acyl chain
      conformations implies that modulation of the acyl chain asymmetry will have an
      opposite effect on the thermotropic phase behavior of PG and PC. For example, it
      is expected, based on the crystal structures, that C(15):C(13)PG should have a
      higher main phase transition temperature (Tm) than C(14):C(14)PG, and
      C(13):C(15)PG should have a lower Tm than C(14):C(14)PG. However, our DSC studies
      show clearly that the expectation is not borne out by experimental data. Rather,
      the Tm values of C(15):C(13)PG, C(14):C(14)PG, and C(13):C(15)PG are 18.2 degrees
      C, 23.1 degrees C, and 24.4 degrees C, respectively. Several other PGs, each with
      a unique acyl chain composition, have also been studied in this laboratory using
      high-resolution DSC. It is shown that the acyl chain conformation of fully
      hydrated PG in general is nearly opposite to that seen in the PG crystal
      structure.

PMID- 10076041
TI  - Partitioning of triphenylalkylphosphonium homologues in gel bead-immobilized
      liposomes: chromatographic measurement of their membrane partition coefficients.
AB  - Unilamellar liposomes of small or large size, SUVs and LUVs, respectively, were
      stably immobilized in the highly hydrophilic Sepharose 4B or Sephacryl S-1000 gel
      beads as a membrane stationary phase for immobilized liposome chromatography
      (ILC). Lipophilic cations of triphenylmethylphosphonium and
      tetraphenylphosphonium (TPP+) have been used as probes of the membrane potential
      of cells. Interaction of TPP+ and triphenylalkylphosphonium homologues with the
      immobilized liposomal membranes was shown by their elution profiles on both zonal
      and frontal ILC. Retardation of the lipophilic cations on the liposome gel bed
      was increased as the hydrophobicity of the cations increased, indicating the
      partitioning of lipophilic cations into the hydrocarbon region of the membranes.
      The cations did not retard on the Sepharose or Sephacryl gel bed without
      liposomes, confirming that the cations only interact with the immobilized
      liposomes. Effects of the solute concentration, flow rate, and gel-matrix
      substance on the ILC were studied. The stationary phase volume of the liposomal
      membranes was calculated from the volume of a phospholipid molecule and the
      amount of the immobilized phospholipid, which allowed us to determine the
      membrane partition coefficient (KLM) for the lipophilic cations distributed
      between the aqueous mobile and membrane stationary phases. The values of KLM were
      generally increased with the hydrophobicity of the solutes increased, and were
      higher for the SUVs than for the LUVs. The ILC method described here can be
      applied to measure membrane partition coefficients for other lipophilic solutes
      (e.g., drugs).

PMID- 10076042
TI  - Cloning and characterization of the transport modifier RS1 from rabbit which was
      previously assumed to be specific for Na+-D-glucose cotransport.
AB  - Previously we cloned membrane associated polypeptides from pig and man (pRS1,
      hRS1) which altered rate and glucose dependence of Na+-d-glucose cotransport
      expressed by SGLT1 from rabbit and man. This paper describes the cloning of a
      related cDNA sequence from rabbit intestine (rbRS1) which encodes a gene product
      with about 65% amino acid identity to pRS1 and hRS1. Hybridization of
      endonuclease-restricted genomic DNA with cDNA fragments of rbRS1 showed that
      there is only one gene with similarity to rbRS1 in rabbit, and genomic PCR
      amplifications revealed that the rbRS1 gene is intronless. Comparing the
      transcription of rbRS1 and rbSGLT1 in various tissues and cell types, different
      mRNA patterns were obtained for both genes. In Xenopus oocytes the Vmax of
      expressed Na+-d-glucose cotransport was increased or decreased when rbRS1 was
      coexpressed with rbSGLT1 or hSGLT1, respectively. After coexpression with hSGLT1
      the glucose dependence of the expressed transport was changed. By coexpression of
      rbRS1 with the human organic cation transporter hOCT2 the expressed cation uptake
      was not altered; however, the expressed cation uptake was drastically decreased
      when hRS1 was coexpressed with hOCT2. The data show that RS1 can modulate the
      function of transporters with non-homologous primary structures.

PMID- 10076043
TI  - Lipid exchange between mixed micelles of phospholipid and triton X-100.
AB  - If phospholipase catalyzed hydrolysis of phospholipid dissolved in a detergent
      mixed micelle is limited to the phospholipid carried by a single micelle, then
      hydrolysis ceases upon exhaustion of that pool. However, if the rate of
      phospholipid exchange between micelles exceeds the catalytic rate then all of the
      phospholipid is available for hydrolysis. To determine phospholipid availability
      we studied the exchange of 1,2-dioleoyl-sn-glycero-3-phosphocholine between mixed
      micelles of phospholipid and non-ionic Triton detergents by both stopped-flow
      fluorescence-recovery and nuclear magnetic resonance-relaxation techniques.
      Stopped-flow analysis was performed by combining mixed micelles of Triton and
      phospholipid with mixed micelles that contained the fluorescent phospholipid 1
      palmitoyl-2-(12-[{7-nitro-2-1, 3-benzoxadiazo-4-yl}amino]dodecanoyl)-sn-glycero-3
      phosphocholine (P-2-NBD-PC). The concentration dependence of fluorescence
      recovery suggested a second-order exchange mechanism that was saturable. The true
      second-order rate constant depends on the specific mechanism for exchange, which
      was not determined in this study, but the rate constant will be on the order of
      106 to 107 M-1s-1. Incorporation of 1-palmitoyl-2-(16
      doxylstearoyl)phosphatidylcholine into micelles increased the rate of proton
      relaxation and gave a limiting relaxation time of 1.3 ms. The results demonstrate
      that phospholipid exchange was rapid and that the phospholipid content of a
      single micelle did not limit the rate of phospholipid hydrolysis by
      phospholipases.

PMID- 10076044
TI  - Nongenomic steroidal modulation of high-affinity serotonin transport.
AB  - The ability of steroids to modulate high-affinity 5-HT transport was investigated
      using cell-based models which stably manifest all known properties of this
      transport system. beta-Estradiol (E2) exhibited noncompetitive, and possibly
      allosteric, inhibition of both radiolabeled serotonin ([3H]5-HT) transport by,
      and radiolabeled cocaine congener ([3H]CFT) binding to, this system. Such
      inhibitory effects were observed within short time courses and unlikely to result
      from genomic effects normally ascribed to estrogen action. Rather, such
      nongenomic effects on 5-HT uptake were more akin to modulatory effects of select
      steroid metabolites on other plasma membrane systems such as neurotransmitter
      receptors and ionic channels. Beyond E2, preliminary examination of other steroid
      metabolites and synthetic steroid receptor agonists/antagonists revealed that
      inhibition of 5-HT transport is additionally attributable only to estriol (E3, an
      E2 metabolite) and tamoxifen (a nonsteroidal, E2 receptor antagonist). These
      findings indicate that the present form of transport modulation is only rendered
      by select compounds and not a general property of steroidal and related agents.
      Assessments of covalent conjugates of E2 suggested that E2 interacts with the
      transporter protein at allosteric site(s) inaccessible from the extracellular
      domain. These findings collectively suggest that steroid-mediated regulation of 5
      HT transport may be a physiologically relevant mechanism, and that antidepressant
      as well as psychostimulant effects in vivo may contain a steroidal component.

PMID- 10076045
TI  - Heparin influence on alpha-staphylotoxin formed channel.
AB  - The effects of heparin on ion channels formed by Staphylococcus aureus alpha
      toxin (ST channel) in lipid bilayers were studied under voltage clamp conditions.
      Heparin concentrations as small as 100 pM induced a sharp dose-dependent increase
      in channel voltage sensitivity. This was only observed when heparin was added to
      the negative-potential side of lipid bilayers in the presence of divalent
      cations. Divalent cations differ in their efficiency: Zn2+>Ca2+>Mg2+. The
      apparent positive gating charge increased 2-3-fold with heparin addition as well
      as with acidification of the bathing solution. 'Free' carboxyl groups and
      carboxyl groups in ion pairs of the protein moiety are hypothesized to interact
      with sulfated groups of heparin through divalent cation bridges. The cis mouth of
      the channel (that protrudes beyond the membrane plane on the side of ST addition
      and to which voltage was applied) is less sensitive to heparin than the trans
      mouth. It is suggested that charged residues which interact with heparin at the
      cis mouth of ST channels and which contribute to the effective gating charge at
      negative voltage may be physically different from those at the trans mouth and at
      positive voltage.

PMID- 10076046
TI  - An ordered metastable phase in hydrated phosphatidylethanolamine: the Y
      transition.
AB  - By using time-resolved X-ray diffraction, differential scanning calorimetry and
      scanning densitometry, we observed rapid formation at low temperature of a
      metastable ordered phase, termed LR1 phase, in fully hydrated
      dihexadecylphosphatidylethanolamine (DHPE). The LR1 phase has the same lamellar
      repeat period as the gel Lbeta phase but differs from the latter in its more
      ordered, orthorhombic hydrocarbon chain arrangement. It forms at about 12 degrees
      C upon cooling and manifests itself as splitting of the sharp, symmetric wide
      angle X-ray peak of the DHPE gel phase into two reflections. This transition,
      designated the 'Y-transition', is readily reversible and proceeds with almost no
      hysteresis between cooling and heating scans. Calorimetrically, the LR1-->Lbeta
      transition is recorded as a low-enthalpy (0.2 kcal/mol) endothermic event. The
      formation of the LR1 phase from the gel phase is associated with a small, about 2
      microl/g, decrease of the lipid partial specific volume recorded by scanning
      densitometry, in agreement with a volume calculation based on the X-ray data. The
      formation of the equilibrium Lc phase was found to take place from within the LR1
      phase. This appears to be the only observable pathway for crystallisation of DHPE
      upon low-temperature incubation. Once formed, the Lc phase of this lipid converts
      directly into Lbeta phase at 50 degrees C, skipping the LR1 phase. Thus, the LR1
      phase of DHPE can only be entered by cooling of the gel Lbeta phase. The data
      disclose certain similarities between the low-temperature polymorphism of DHPE
      and that of long-chain normal alkanes.

PMID- 10076047
TI  - Signal perception and transduction: the role of protein kinases.
AB  - Cells can react to environmental changes by transduction of extracellular
      signals, to produce intracellular responses. Membrane-impermeable signal
      molecules are recognized by receptors, which are localized on the plasma membrane
      of the cell. Binding of a ligand can result in the stimulation of an intrinsic
      enzymatic activity of its receptor or the modulation of a transducing protein.
      The modulation of one or more intracellular transducing proteins can finally lead
      to the activation or inhibition of a so-called 'effector protein'. In many
      instances, this also results in altered gene expression. Phosphorylation by
      protein kinases is one of the most common and important regulatory mechanisms in
      signal transmission. This review discusses the non-channel transmembrane
      receptors and their downstream signaling, with special focus on the role of
      protein kinases.

PMID- 10076048
TI  - Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34
      cells via the suppression of the formation of megamitochondria.
AB  - Toxic effects of chloramphenicol, an antibiotic inhibitor of mitochondrial
      protein synthesis, on rat liver derived RL-34 cell line were completely blocked
      by a combined treatment with substances endowed with direct or indirect
      antioxidant properties. A stable, nitroxide free radical scavenger, 4-hydroxy
      2,2,6, 6-tetramethylpiperidine-1-oxyl, and a protein synthesis inhibitor,
      cycloheximide, suppressed in a similar manner the following manifestations of the
      chloramphenicol cytotoxicity: (1) Oxidative stress state as evidenced by FACS
      analysis of cells loaded with carboxy-dichlorodihydrofluorescein diacetate and
      Mito Tracker CMTH2MRos; (2) megamitochondria formation detected by staining of
      mitochondria with MitoTracker CMXRos under a laser confocal microscopy and
      electron microscopy; (3) apoptotic changes of the cell detected by the phase
      contrast microscopy, DNA laddering analysis and cell cycle analysis. Since
      increases of ROS generation in chloramphenicol-treated cells were the first sign
      of the chloramphenicol toxicity, we assume that oxidative stress state is a
      mediator of above described alternations of RL-34 cells including MG formation.
      Pretreatment of cells with cycloheximide or 4-hydroxy-2,2, 6,6
      tetramethylpiperidine-1-oxyl, which is known to be localized into mitochondria,
      inhibited the megamitochondria formation and succeeding apoptotic changes of the
      cell. Protective effects of cycloheximide, which enhances the expression of Bcl-2
      protein, may further confirm our hypothesis that the megamitochondria formation
      is a cellular response to an increased ROS generation and raise a possibility
      that antiapoptotic action of the drug is exerted via the protection of the
      mitochondria functions.

PMID- 10076049
TI  - Cyclosporine-induced renal artery smooth muscle contraction is associated with
      increases in the phosphorylation of specific contractile regulatory proteins.
AB  - Cyclosporine A (CSA) is a type 2B phosphatase inhibitor which can induce
      contraction of renal artery smooth muscle. In this investigation, we examined the
      phosphorylation events associated with CSA-induced contraction of bovine renal
      artery smooth muscle. Contractile responses were determined in a muscle bath and
      the corresponding phosphorylation events were determined with whole cell
      phosphorylation and two-dimensional gel electrophoresis. CSA-induced contractions
      were associated with increases in the phosphorylation of the 20 kDa myosin light
      chains (MLC20) and different isoforms of the small heat shock protein, HSP27.
      Cyclic nucleotide-dependent relaxation of CSA-induced contractions was associated
      with increases in the phosphorylation of another small heat shock protein, HSP20,
      and decreases in the phosphorylation of the MLC20, and some isoforms of HSP27.
      These data suggest that CSA-induced contraction and relaxation of vascular smooth
      muscle is associated with increases in the phosphorylation of specific
      contractile regulatory proteins.

PMID- 10076050
TI  - Purification and characterization of TEF1, a transcription factor that controls
      the human transforming growth factor-alpha promoter.
AB  - Transforming growth factor-alpha (TGF-alpha) is a member of the epidermal growth
      factor family. It activates signal transduction pathways leading to cell
      proliferation through the interaction with cell surface epidermal growth factor
      receptor. The overexpression of TGF-alpha has been found in many types of cancers
      and is thought to be involved in the genesis and maintenance of these tumors.
      Recent results also implicate this growth factor in the development of certain
      diabetic complications, such as atherosclerosis. The function of TGF-alpha can be
      tightly controlled at the level of transcription of its gene. We have previously
      characterized the proximal TGF-alpha promoter and identified two neighboring
      regulatory elements that appeared to cooperate with each other in the regulation
      of TGF-alpha transcription. The transcription factor that functions through the
      distal element was identified as AP-2, a protein that was found to be induced by
      the oncoprotein, Ras. However, what factor binds and controls the proximal
      regulatory element (PRE) is still unclear. Here, we report the purification and
      preliminary characterization of the PRE-binding transcription factor TEF1 by
      sequence-specific DNA-affinity chromatography from rat kidney nuclear extracts.
      The purified TEF1 migrates on the SDS-PAGE at a molecular mass of about 36 kDa.
      It specifically interacts with the PRE and was able to strongly activate
      transcription from the TGF-alpha promoter in HeLa cell nuclear extracts in an in
      vitro transcription assay. The UV cross-linking experiment confirmed that this 36
      kDa protein is indeed the protein that specifically binds the PRE. We also show
      that the spacing between the AP-2 and the TEF1 sites in the TGF-alpha promoter
      has little effect on the transcription from the TGF-alpha promoter. The
      purification of TEF1 furthers our understanding of how TGF-alpha expression is
      regulated and may help us understand the upstream signaling events that lead to
      the elevated expression of this growth factor.

PMID- 10076051
TI  - Expression of the hepatocyte growth factor-like protein gene in human
      hepatocellular carcinoma and interleukin-6-induced increased expression in
      hepatoma cells.
AB  - Human hepatocellular carcinoma is one of the most frequent malignant tumors. It
      may occur following exposure to various agents, including viruses and chemical
      carcinogens; however, the underlying mechanisms of the hepatocarcinogenesis are
      not known. The present study is the result of our search for genes which may be
      abundantly expressed in human primary liver carcinoma. One of these genes was
      found to encode the human hepatocyte growth factor-like protein (HGFLP), also
      known as macrophage-stimulating protein. HGFLP is structurally homologous to
      hepatocyte growth factor, a potent growth factor for liver. HGFLP mRNA was also
      found to be overexpressed in a hepatoblastoma sample and in a sample of subacute
      fulminant hepatic necrosis. In a study on the effects of cytokines on the
      expression of HGFLP, we found that IL-6 increased expression of HGFLP mRNA in Hep
      G2 cells, but IL-1alpha, IL-1beta and TNF-alpha had no effect. An increase in
      HGFLP could be the result of inflammation and/or tissue injury and its
      overexpression may prove to be useful as an indicator of hepatoma.

PMID- 10076052
TI  - Glucose metabolism in Neurospora is altered by heat shock and by disruption of
      HSP30.
AB  - We compared the metabolism of [1-13C]glucose by wild type cells of Neurospora
      crassa at normal growth temperature and at heat shock temperatures, using nuclear
      magnetic resonance analysis of cell extracts. High temperature led to increased
      incorporation of 13C into trehalose, relative to all other metabolites, and there
      was undetectable synthesis of glycerol, which was a prominent metabolite of
      glucose at normal temperature (30 degrees C). Heat shock strongly reduced
      formation of tricarboxylic acid cycle intermediates, approximately 10-fold, and
      mannitol synthesis was severely depressed at 46 degrees C, but only moderately
      reduced at 45 degrees C. A mutant strain of N. crassa that lacks the small alpha
      crystallin-related heat shock protein, Hsp30, shows poor survival during heat
      shock on a nutrient medium with restricted glucose. An analysis of glucose
      metabolism of this strain showed that, unlike the wild type strain, Hsp30
      deficient cells may accumulate unphosphorylated glucose at high temperature. This
      suggestion that glucose-phosphorylating hexokinase activity might be depressed in
      mutant cells led us to compare hexokinase activity in the two strains at high
      temperature. Hexokinase was reduced more than 35% in the mutant cell extracts,
      relative to wild type extracts. alpha-Crystallin and an Hsp30-enriched
      preparation protected purified hexokinase from thermal inactivation in vitro,
      supporting the proposal that Hsp30 may directly stabilize hexokinase in vivo
      during heat shock.

PMID- 10076053
TI  - Interleukin-4 (IL-4), but not IL-10, regulates the synthesis of IL-6, IL-8 and
      leukemia inhibitory factor by human bone marrow stromal cells.
AB  - Leukemia inhibitory factor (LIF), interleukin 6 (IL-6) and IL-8 are important
      regulators of inflammation and hematopoiesis. Human bone marrow stromal cells
      regulate marrow hematopoiesis by secreting cytokines. By using reverse
      transcriptase polymerase chain reaction (RT-PCR), we demonstrate that human bone
      marrow stromal cells constitutively express LIF, IL-6 and IL-8 transcripts. By
      using specific ELISAs, we found that their spontaneous productions of LIF, IL-6
      and IL-8 are elevated in response to serum and after stimulation with the pro
      inflammatory cytokines IL-1alpha and TNF-alpha. The anti-inflammatory cytokine IL
      4 reduces their serum- and cytokine-induced LIF secretion. By contrast, IL-4
      stimulates their serum- and IL-1alpha-induced IL-6 synthesis. IL-4 has no effect
      on the serum-induced IL-8 synthesis by marrow stromal cells, but stimulates their
      cytokine-induced IL-8 production. The anti-inflammatory cytokine IL-10 has no
      effect on the serum- and cytokine-induced LIF, IL-6 and IL-8 synthesis by bone
      marrow stromal cells. RT-PCR experiments reveal the presence of IL-4 receptor
      alpha-chain mRNA and IL-10 receptor mRNA in cultured bone marrow stromal cells.
      The differential regulation by IL-4 of two related cytokines, such as LIF and IL
      6, and the enhanced effect of this 'anti-inflammatory' cytokine on IL-6 and IL-8
      synthesis highlight the tightly controlled regulation and the complexity of the
      cytokine production within the human bone marrow.

PMID- 10076054
TI  - Effects of lithium on pigmentation in the embryonic zebrafish (Brachydanio
      rerio).
AB  - Pigment cell precursors of the embryonic zebrafish give rise to melanophores,
      xanthophores and/or iridophores. Cell signaling mechanisms related to the
      development of pigmentation remain obscure. In order to examine the mechanisms
      involved in pigment cell signaling, we treated zebrafish embryos with various
      activators and inhibitors of signaling pathways. Among those chemicals tested,
      LiCl and LiCl/forskolin had a stimulatory effect on pigmentation, most notable in
      the melanophore population. We propose that the inositol phosphate (IP) pathway,
      is involved in pigment pattern formation in zebrafish through its involvement in
      the: (1) differentiation/proliferation of melanophores; (2) dispersion of
      melanosomes; and/or (3) synthesis/deposition of melanin. To discern at what level
      pigmentation was being effected we: (1) counted the number of melanophores in
      control and experimental animals 5 days after treatment; (2) measured tyrosinase
      activity and melanin content; and (3) employed immunoblotting techniques with
      anti-tyrosine-related protein-2 and anti-melanocyte-specific gene-1 as
      melanophore-specific markers. Although gross pigmentation increased dramatically
      in LiCl- and LiCl/forskolin treated embryos, the effect on pigmentation was not
      due to an increase in the proliferation of melanophores, but was possibly through
      an increase in melanin synthesis and/or deposition. Collectively, results from
      these studies suggest the involvement of an IP-signaling pathway in the
      stimulation of pigmentation in embryonic zebrafish through the
      synthesis/deposition of melanin within the neural crest-derived melanophores.

PMID- 10076055
TI  - Tobacco BY-2 cell-free extracts induce the recovery of microtubule nucleating
      activity of inactivated mammalian centrosomes.
AB  - The structure and the molecular composition of the microtubule-organizing centers
      in acentriolar higher plant cells remain unknown. We developed an in vitro
      complementation assay where tobacco BY-2 extracts can restore the microtubule
      nucleating activity of urea-inactivated mammalian centrosomes. Our results
      provide first evidence that soluble microtubule-nucleating factors are present in
      the plant cytosolic fraction. The implication for microtubule nucleation in
      higher plants is discussed.

PMID- 10076056
TI  - Ups and downs of protein crystallization: studies of protein crystals by high
      performance capillary electrophoresis.
AB  - High-performance capillary electrophoresis is a high-technology micro-separation
      method. Short run time, full automation and minute amounts of sample make it a
      very attractive technique. In this report we describe studies of protein crystals
      by capillary electrophoresis. We show how high-performance capillary
      electrophoresis can be used effectively for rapid evaluation and examination of
      the protein solution used for crystallization, the protein crystals (solubilized)
      and surrounding mother liquor. With coated capillaries, the runs were
      reproducible and disturbing effects, such as electroendosmosis and interaction of
      the proteins with the capillary wall, were suppressed efficiently. We recommend
      this new technique as a powerful and routine companion to protein
      crystallography.

PMID- 10076057
TI  - Manganese-containing superoxide dismutase and its gene from Candida albicans.
AB  - Mitochondrial manganese-containing superoxide dismutase was purified around 112
      fold with an overall yield of 1.1% to apparent electrophoretic homogeneity from
      the dimorphic pathogenic fungus, Candida albicans. The molecular mass of the
      native enzyme was 106 kDa and the enzyme was composed of four identical subunits
      with a molecular mass of 26 kDa. The enzyme was not sensitive to either cyanide
      or hydrogen peroxide. The N-terminal amino acid sequence alignments (up to the
      18th residue) showed that the enzyme has high similarity to the other eukaryotic
      manganese-containing superoxide dismutases. The gene sod2 encoding manganese
      containing superoxide dismutase has been cloned using a product obtained from
      polymerase chain reaction. Sequence analysis of the sod2 predicted a manganese
      containing superoxide dismutase that contains 234 amino acid residues with a
      molecular mass of 26173 Da, and displayed 57% sequence identity to the homologue
      of Saccharomyces cerevisiae. The deduced N-terminal 34 amino acid residues may
      serve as a signal peptide for mitochondrial translocation. Several regulatory
      elements such as stress responsive element and haem activator protein 2/3/4/5
      complex binding sites were identified in the promoter region of sod2. Northern
      analysis with a probe derived from the cloned sod2 revealed a 0.94-kb band, which
      corresponds approximately to the expected size of mRNA deduced from sod2.

PMID- 10076058
TI  - Pharmacokinetics and disposition characteristics of recombinant decorin after
      intravenous injection into mice.
AB  - The pharmacokinetics and disposition characteristics of recombinant decorin after
      intravenous administration were investigated in mice. Following bolus injection
      of 111In-labeled decorin at doses of 0.02 and 0.1 mg/kg, radioactivity rapidly
      disappeared from the circulation and approximately 70% of the dose accumulated in
      liver within 10 min. 111In-labeled decorin was preferentially localized in
      hepatic nonparenchymal cells. At a higher dose of 1 mg/kg, clearance from the
      circulation and hepatic uptake of [111In]decorin were slower than at lower doses.
      Both the accumulation in other tissues and urinary excretion of [111In]decorin
      were 5% or less. Pharmacokinetic analysis demonstrated that hepatic uptake
      clearance was large and accounted almost completely for total body clearance; in
      addition the clearance values decreased as the dose increased, suggesting that
      the hepatic uptake of decorin is mediated by a specific mechanism which becomes
      saturated at higher doses. In competitive inhibition experiments, hepatic uptake
      of 111In-labeled decorin was partially inhibited (about 20-30%) by several
      sulfated glycans such as glycosaminoglycans and dextran sulfate and by
      mannosylated bovine serum albumin (BSA), mannan and mannose to a lesser extent
      (about 10%). On the other hand, polyinosinic acid, polycytidylic acid and
      succinylated BSA were ineffective, suggesting that the scavenger receptor for
      polyanions in the liver is not involved in the hepatic uptake of decorin. A basic
      protein, protamine, and a ligand of the apoE receptor, lactoferrin, also had no
      effect. Taken together, the present results have demonstrated that recombinant
      decorin is rapidly eliminated from the blood circulation through extensive uptake
      by the liver, primarily by the nonparenchymal cells, following systemic
      administration. The sugar structure and mannose residue in decorin have also been
      suggested to play an important role in the hepatic uptake of decorin. These
      findings provide useful information for the development of decorin as a
      therapeutic agent.

PMID- 10076059
TI  - NMR study of the metabolic 15N isotopic enrichment of cyanophycin synthesized by
      the cyanobacterium Synechocystis sp. strain PCC 6308.
AB  - 1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopy has been used to
      characterize cyanophycin, a multi-l-arginyl-poly-[l-aspartic acid] polypeptide
      from the cyanobacterium Synechocystis sp. strain PCC 6308. 1H, 13C and 15N
      chemical shifts and 1JHN and 1JCN coupling constants were measured in isolated
      15N-labeled cyanophycin, and showed chemical shift values and J-couplings
      consistent with the reported polypeptide structure. 15N enrichment levels were
      determined from the extent of 1H-15N J-coupling in 1H NMR spectra of cyanophycin.
      Similar experiments using 13C-15N coupling in 13C NMR spectra were not useful in
      determining enrichment levels.

PMID- 10076060
TI  - Isolation and identification of three bactericidal domains in the bovine alpha
      lactalbumin molecule.
AB  - Proteolytic digestion of alpha-lactalbumin by pepsin, trypsin and chymotrypsin
      yielded three polypeptide fragments with bactericidal properties. Two fragments
      were obtained from the tryptic digestion. One was a pentapeptide with the
      sequence EQLTK (residues 1-5) and the other, GYGGVSLPEWVCTTF ALCSEK (residues (17
      31)S-S(109-114)), was composed of two polypeptide chains held together by a
      disulfide bridge. Fragmentation of alpha-lactalbumin by chymotrypsin yielded
      CKDDQNPH ISCDKF (residues (61-68)S-S(75-80)), also a polypeptide composed of two
      polypeptide chains held together by a disulfide bridge. The three polypeptides
      were synthesized and found to exert antimicrobial activities. The polypeptides
      were mostly active against Gram-positive bacteria. Gram-negative bacteria were
      only poorly susceptible to the bactericidal action of the polypeptides.
      GYGGVSLPEWVCTTF ALCSEK was most, EQLTK least bactericidal. Replacement of leucine
      (23) with isoleucine, having a similar chemical structure but higher
      hydrophobicity, in the sequence GYGGVSLPEWVCTTF ALCSEK significantly reduced the
      bactericidal capacity of the polypeptide. Digestion of alpha-lactalbumin by
      pepsin yielded several polypeptide fragments without antibacterial activity.
      alpha-Lactalbumin in contrast to its polypeptide fragments was not bactericidal
      against all the bacterial strains tested. Our results suggest a possible
      antimicrobial function of alpha-lactalbumin after its partial digestion by
      endopeptidases.

PMID- 10076061
TI  - Assessment of the effects of cetylpyridium chloride on water content of the
      collagen-keratocyte matrix of the mammalian corneal stroma ex vivo.
AB  - The effects of cationic surfactants on the time-dependent increases in hydration
      of the corneal stroma were investigated to assess if the contribution of the
      proteoglycans could be titrated and how it might relate to the maximum and
      minimum swelling properties of the corneal stroma. From recent post-mortem eyes
      from adult sheep, square (8 x 8 mm) samples of corneal stroma were prepared and
      incubated in isotonic neutral pH mixed salts solution with added glucose, or pure
      water, at 37 degrees C. The time-dependent changes in wet mass were assessed over
      24 h in the absence or presence of 0. 001-2% w/v cetylpyridium chloride (CPC) or
      benzalkonium chloride (BAC). The rate and magnitude of stromal swelling was
      reduced in a concentration-dependent fashion by the surfactants. In mixed salts
      solution, 100% inhibition of swelling could be achieved at 2% CPC and BAC. In
      pure water, the relative swelling was much more substantial and could only be
      attenuated by CPC.

PMID- 10076062
TI  - Range of activity and metabolic stability of synthetic antibacterial
      glycopeptides from insects.
AB  - Antibacterial glycopeptides isolated from insects are exciting bio-oligomers
      because they represent a family of compounds in which the structural and
      functional effects of incorporating short O-linked sugars to protein fragments
      can be studied. Additionally, their high activity in vitro warrants detailed
      further drug development efforts. Due to the limited availability of the isolated
      material, we used synthetic glycopeptides and some analogs to investigate the
      range of activity of drosocin and pyrrhocoricin. While addition of the Gal-GalNAc
      disaccharide to the natural mid-chain position generally increased the
      antibacterial activity of drosocin, pyrrhocoricin lacking sugar appeared to be
      more potent, with an IC50 against Escherichia coli D22 of 150 nM. Although
      glycosylated drosocin was active against E. coli in the low microM range in
      vitro, this peptide was completely inactive when injected into mice. The lack of
      in vivo activity of drosocin could be explained by the unusually high degradation
      rate of the peptides in mammalian sera. The early degradation products were
      inactive in vitro. In contrast, the peptides were considerably more stable in
      insect hemolymph, where their natural activity is manifested.

PMID- 10076063
TI  - Identification of a human cDNA encoding a novel protein structurally related to
      the yeast membrane-associated metalloprotease, Ste24p.
AB  - Recently, a novel membrane-associated metalloprotease, designated Ste24p, has
      been identified in Saccharomyces cerevisiae [K. Fujimura-Kamada, F.J. Nouvet, S.
      Michaelis, J. Cell Biol. 27 (1997) 271-285]. We cloned a human brain cDNA
      encoding a protein homologous to Ste24p (designated Hs Ste24p). The predicted 475
      amino acid product of its open reading frame exhibited 62% similarity to Ste24p,
      and contained a zinc metalloprotease motif (HEXXH) and multiple predicted
      membrane spans. Northern blot analysis showed that this gene was expressed in
      most tissues. Immunofluorescence analysis of epitope-tagged Hs Ste24p constructs
      suggested that it is localized in the ER and possibly also in the Golgi
      compartment. A search of the expression sequence tag database identified a
      fragment of DNA encoding a segment homologous to the segment of Hs Ste24p
      containing the HEXXH motif in insects and nematodes. Thus, Hs Ste24p could be a
      member of a new family of Ste24p-like membrane-associated metalloproteases which
      are widely conserved in eukaryotes.

PMID- 10076064
TI  - EPR spin trapping and 2-deoxyribose degradation studies of the effect of
      pyridoxal isonicotinoyl hydrazone (PIH) on *OH formation by the Fenton reaction.
AB  - The search for effective iron chelating agents was primarily driven by the need
      to treat iron-loading refractory anemias such as beta-thalassemia major. However,
      there is a potential for therapeutic use of iron chelators in non-iron overload
      conditions. Iron can, under appropriate conditions, catalyze the production of
      toxic oxygen radicals which have been implicated in numerous pathologies and,
      hence, iron chelators may be useful as inhibitors of free radical-mediated tissue
      damage. We have developed the orally effective iron chelator pyridoxal
      isonicotinoyl hydrazone (PIH) and demonstrated that it inhibits iron-mediated
      oxyradical formation and their effects (e.g. 2-deoxyribose oxidative degradation,
      lipid peroxidation and plasmid DNA breaks). In this study we further
      characterized the mechanism of the antioxidant action of PIH and some of its
      analogs against *OH formation from the Fenton reaction. Using electron
      paramagnetic resonance (EPR) with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) as a
      spin trap for *OH we showed that PIH and salicylaldehyde isonicotinoyl hydrazone
      (SIH) inhibited Fe(II)-dependent production of *OH from H2O2. Moreover, PIH
      protected 2-deoxyribose against oxidative degradation induced by Fe(II) and H2O2.
      The protective effect of PIH against both DMPO hydroxylation and 2-deoxyribose
      degradation was inversely proportional to Fe(II) concentration. However, PIH did
      not change the primary products of the Fenton reaction as indicated by EPR
      experiments on *OH-mediated ethanol radical formation. Furthermore, PIH
      dramatically enhanced the rate of Fe(II) oxidation to Fe(III) in the presence of
      oxygen, suggesting that PIH decreases the concentration of Fe(II) available for
      the Fenton reaction. These results suggest that PIH and SIH deserve further
      investigation as inhibitors of free-radical mediated tissue damage.

PMID- 10076065
TI  - Relative quantification of glycated Cu-Zn superoxide dismutase in erythrocytes by
      electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESIMS) was used for relative
      quantification of glycated Cu-Zn superoxide dismutase (SOD-1) in human
      erythrocytes. SOD-1 samples were prepared from erythrocytes by removing
      hemoglobin using hemoglobind gel followed by ethanol and chloroform extraction.
      The reproducibility in measurement of the relative percentage of glycated protein
      was good, and the standard deviation of each measurement was 4.0%. From the mass
      spectral analysis of a mixture of commercial SOD-1 and in vitro partially
      glycated SOD-1 in several ratios, it was found that free and glycated SOD-1 have
      the same ionization efficiencies. The percentage of glycation on SOD-1 was
      measured in 30 individuals, including patients with diabetes mellitus. The
      glycation levels ranged from 4.5% to below the detection limit. The SOD-1 sample
      extracted from erythrocytes was fractionated by Glyco-Gel B chromatography, and
      the separated fractions were analyzed by MS. The mass spectra of absorbed
      fraction showed significant amounts of non-specific binding of non-glycated
      proteins to Glyco-Gel B.

PMID- 10076066
TI  - Enhanced gluconeogenesis and hepatic insulin resistance in insulin-like growth
      factor binding protein-1 transgenic mice.
AB  - Fasting hyperglycemia is observed in transgenic mice which overexpress insulin
      like growth factor binding protein-1. In an attempt to understand the mechanisms
      underlying this observation we have examined glycogenolysis and gluconeogenesis
      in isolated hepatocytes from wild-type and transgenic mice. Glucose production
      from pyruvate was significantly less responsive to inhibition by insulin in
      hepatocytes from transgenic mice compared to hepatocytes from wild-type mice.
      Serum from transgenic mice resulted in more glucose production by hepatocytes
      than serum from wild-type mice. Serum alanine was increased while serum lactate
      was significantly reduced in transgenic mice compared to wild-type mice. Serum
      free fatty acids and beta-hydroxybutyrate were similar in both groups of mice.
      These data suggest that fasting hyperglycemia is due to enhanced gluconeogenesis,
      hepatic insulin resistance and increased serum gluconeogenic substrate in
      transgenic mice.

PMID- 10076067
TI  - Cell adhesion activity for murine carcinoma cells of a wheat germ 55-kDa protein
      with binding affinity for animal extracellular matrix proteins.
AB  - A wheat germ 55-kDa protein was isolated by affinity chromatography with Matrigel
      immobilized on agarose, followed by preparative gel electrophoresis. This
      Matrigel-binding protein designated as WG-55 had an amino-terminal amino acid
      sequence which is identical to that of a putative mature form of wheat storage
      protein Gbl 1. WG-55 reacted with concanavalin A, indicating its glycoprotein
      nature as expected from the amino acid sequence of Gbl 1. As expected, similarly,
      WG-55 exhibited RGD-dependent cell adhesion activity for murine carcinoma cells.
      These data suggest that WG-55 or mature Gbl 1 protein may play a role in plant
      cell adhesion.

PMID- 10076068
TI  - Tissue-specific distribution of breast-muscle-type and leg-muscle-type troponin T
      isoforms in birds.
AB  - In order to show the tissue-specific distribution of troponin T (TnT) isoforms in
      avian skeletal muscles, their expression was examined by electrophoresis of the
      breast and leg muscles of seven avian species and immunoblotting with the
      antiserum against fast skeletal muscle TnT. It has been reported in the chicken
      that breast-muscle-type (B-type) and leg-muscle-type (L-type) TnT isoforms are
      expressed specifically in the adult breast and leg muscles, respectively. Their
      differential expression patterns were confirmed in all birds examined in this
      study. The expression of a segment encoded by the exon x series of TnT was also
      examined by immunoblotting with the antiserum against a synthetic peptide derived
      from the exon x3 sequence, because the segment has been shown to be included
      exclusively in the B-type, but not in the L-type TnT. The expression of the
      segment was found only in the breast muscle, but not in the leg muscle of all
      birds examined. TnT cDNA sequences from the duck breast and leg muscles were
      determined and showed that only B-type TnT had an exon x-related sequence,
      suggesting that the expression of B-type TnT containing the exon x-derived
      segment is conserved consistently in the birds.

PMID- 10076069
TI  - Amino acid residues involved in the catalytic mechanism of NAD-dependent
      glutamate dehydrogenase from Halobacterium salinarum.
AB  - The pH dependence of kinetic parameters for a competitive inhibitor (glutarate)
      was determined in order to obtain information on the chemical mechanism for NAD
      dependent glutamate dehydrogenase from Halobacterium salinarum. The maximum
      velocity is pH dependent, decreasing at low pHs giving a pK value of 7.19+/-0.13,
      while the V/K for l-glutamate at 30 degrees C decreases at low and high pHs,
      yielding pK values of 7.9+/-0.2 and 9.8+/-0.2, respectively. The glutarate pKis
      profile decreases at high pHs, yielding a pK of 9. 59+/-0.09 at 30 degrees C. The
      values of ionization heat calculated from the change in pK with temperature are:
      1.19 x 10(4), 5.7 x 10(3), 7 x 10(3), 6.6 x 10(3) cal mol-1, for the residues
      involved. All these data suggest that the groups required for catalysis and/or
      binding are lysine, histidine and tyrosine. The enzyme shows a time-dependent
      loss in glutamate oxidation activity when incubated with diethyl pyrocarbonate
      (DEPC). Inactivation follows pseudo-first-order kinetics with a second-order rate
      constant of 53 M-1min-1. The pKa of the titratable group was pK1=6.6+/-0.6.
      Inactivation with ethyl acetimidate also shows pseudo-first-order kinetics as
      well as inactivation with TNM yielding second-order constants of 1.2 M-1min-1 and
      2.8 M-1min-1, and pKas of 8.36 and 9.0, respectively. The proposed mechanism
      involves hydrogen binding of each of the two carboxylic groups to tyrosyl
      residues; histidine interacts with one of the N-hydrogens of the l-glutamate
      amino group. We also corroborate the presence of a conservative lysine that has a
      remarkable ability to coordinate a water molecule that would act as general base.

PMID- 10076089
TI  - An exploration of varieties of visual attention: ERP findings.
AB  - A set of five tasks was designed to examine dynamic aspects of visual attention:
      selective attention to color, selective attention to pattern, dividing and
      switching attention between color and pattern, and selective attention to pattern
      with changing target. These varieties of visual attention were examined using the
      same set of stimuli under different instruction sets; thus differences between
      tasks cannot be attributed to differences in the perceptual features of the
      stimuli. ERP data are presented for each of these tasks. A within-task analysis
      of different stimulus types varying in similarity to the attended target feature
      revealed that an early frontal selection positivity (FSP) was evident in
      selective attention tasks, regardless of whether color was the attended feature.
      The scalp distribution of a later posterior selection negativity (SN) was
      affected by whether the attended feature was color or pattern. The SN was largely
      unaffected by dividing attention across color and pattern. A large widespread
      positivity was evident in most conditions, consisting of at least three
      subcomponents which were differentially affected by the attention conditions.
      These findings are discussed in relation to prior research and the time course of
      visual attention processes in the brain.

PMID- 10076090
TI  - Visual lateralization and monocular sleep in the domestic chick.
AB  - Behavioural sleep during the first 2 weeks of life was investigated in female
      chicks reared with an imprinting object or in social (visual) isolation.
      Binocular sleep tended to decrease and monocular sleep to increase with age in
      both rearing conditions. In chicks reared with an imprinted object. during the
      first week, monocular sleep with either right or left eye closure occurred with
      approximately the same frequency, except that on day 5 in which right eye closure
      dominated; during the second week, however, there was a clear bias towards more
      monocular sleep with left eye closure. During the second week, the pattern of
      monocular sleep was similar in both rearing conditions, but during the first week
      chicks reared with the imprinting object showed relatively more right eye closure
      compared to chicks reared without the imprinting object, an effect that might
      tentatively be associated with consolidation of imprinting memories in the left
      hemisphere. Binocular sleep occurred in all four body postures adopted by chicks
      during sleep: standing sleep, sleep with bill forward, sleep with bill on the
      ground, and sleep with head on the ground. Monocular sleep, in contrast, only
      occurred when chicks adopted the bill forward posture. When the colour of the
      imprinting object was suddenly changed on day 8, a striking shift towards
      predominant right eye closure during monocular sleep was observed. The same
      occurred when the imprinting object was suddenly removed from the home-cage on
      day 8, but not with other types of changes (i.e., when a novel different object
      was inserted into the home-cage or when a novel-coloured imprinting object was
      inserted into the home-cage together with the original one). It is argued that
      this phenomenon could be associated with right hemisphere involvement in response
      to novelty.

PMID- 10076091
TI  - The lifetime of automatic semantic priming effects may exceed two seconds.
AB  - The N400 component of event-related potentials (ERPs) was obtained in a modified
      version of the Neely [J.H. Neely, Semantic priming and retrieval from lexical
      memory: Roles of inhibitionless spreading activation and limited-capacity
      attention, Journal of Experimental Psychology: General, Vol. 106 (1977), pp. 226
      254.] paradigm which permits unconfounding of semantic priming effects due to
      automatic and attentional processes. It was found that a short stimulus onset
      asynchrony (SOA) of 250 ms between the prime and the target was associated with
      automatic but not expectancy effects on the amplitude of N400. At a long SOA of
      2000 ms between prime and target, semantic priming effects on N400 were obtained
      associated with both automatic and expectancy processes. Moreover, there was no
      significance difference in the magnitude of the automatic effects at the two
      SOAs, suggesting that automatic processing had not decayed within the 2000 ms
      interval between the prime and target. The results support the two-processing
      interpretation of semantic priming advanced by Posner and Synder [M.I. Posner,
      C.R.R. Snyder, Attention and cognitive control, in: R.L. Solso (Ed.), Information
      Processing and Cognition: The Loyola Symposium, Erlbaum, Hillsdale, NJ (1975).]
      and concur with the results of Neely [J.H. Neely, Semantic priming and retrieval
      from lexical memory: Roles of inhibitionless spreading activation and limited
      capacity attention, Journal of Experimental Psychology: General, Vol. 106 (1977),
      pp. 226-254], with the exception of indicating a longer persistence of automatic
      processes.

PMID- 10076092
TI  - The effect of midazolam on the modality-match effect in implicit memory.
AB  - Prominent theories of implicit memory claim that perceptual processes play a
      central role in implicit memory. The modality-match effect, the finding that
      priming is greater when the modality of stimulus presentation matches at study
      and test, provides the central evidence for these approaches. In this paper we
      use the benzodiazepine, midazolam, to explore the nature of the modality-match
      effect in implicit memory. We compared the modality-match effect in a midazolam
      and a saline (i.e., a placebo) condition. Our experimental results demonstrate
      that the modality-match effect is diminished substantially in a midazolam
      condition even though components of priming are preserved. Given the empirically
      validated assumption that midazolam minimizes explicit memory, these results
      suggest that there exist components of implicit memory that are not mediated by
      perceptual processes and raise questions about the generality of prominent
      theories of implicit memory.

PMID- 10076093
TI  - Neurophysiological correlates of the recognition of facial expressions of emotion
      as revealed by magnetoencephalography.
AB  - MEG correlates of the recognition of facial expressions of emotion were studied
      in four healthy volunteers. Subjects performed a facial emotion recognition task
      and a control task involving recognition of complex objects including faces.
      Facial emotion recognition activated inferior frontal cortex, amygdala and
      different parts of temporal cortex in a relatively consistent time sequence. The
      characteristics of these activations were clearly different from those recorded
      during the control task. Most interesting was the fact that faces evoked
      different MEG responses as a function of task demands, i.e., the activations
      recorded during facial emotion recognition were different from those recorded
      during simple face recognition in the control task. These findings support the
      assumption that MEG is able to specifically identify the activation pattern of
      the brain when recognition of the emotional expression of a face is performed.

PMID- 10076094
TI  - 'Paradoxical' alpha synchronization in a memory task.
AB  - The results of a specially designed memory search paradigm which maximizes
      episodic short-term memory (STM) and minimizes semantic long-term memory (LTM)
      demands show that the upper alpha band synchronizes selectively in those
      conditions and time intervals where episodic STM demands are maximal. This
      finding of a selective alpha synchronization occurring only in the upper alpha
      band and during highest task demands is surprising because it is well known that
      usually alpha desynchronizes during mental activity. Because experiments from our
      laboratory indicate that desynchronization in the upper alpha band is related to
      semantic LTM processes, the present finding suggests that a selective
      synchronization in this frequency band reflects inhibition of semantic LTM. It is
      assumed that once the capacity limits of STM are reached or exceeded, processing
      resources are no longer distributed and that potentially interfering, task
      irrelevant, brain areas or processing systems are inhibited.

PMID- 10076095
TI  - Intracranial auditory detection and discrimination potentials as substrates of
      echoic memory in children.
AB  - In children, intracranial responses to auditory detection and discrimination
      processes have not been reported. We, therefore, recorded intracranial event
      related potentials (ERPs) to both standard and deviant tones and/or syllables in
      4 children undergoing pre-surgical evaluation for epilepsy. ERPs to detection
      (mean latency = 63 ms) and discrimination (mean latency = 334 ms) were highly
      localized to areas surrounding the Sylvian fissure (SF). These potentials reflect
      activation of different neuronal populations and are suggested to contribute to
      the scalp recorded auditory N1 and mismatch negativity (MMN).

PMID- 10076096
TI  - Non-specific directional adaptation to asymmetrical visual-vestibular
      stimulation.
AB  - Subjective estimates of passive whole-body rotations in darkness were evaluated
      before and after exposure to asymmetrical incoherent visual-vestibular
      stimulation (VVS). Two subjects who showed large capacity for adaptation to
      symmetrical incoherent VVS were enrolled in the study. Strikingly, after 45 min
      of asymmetrical left-right VVS, perception of rotation decreased equally for
      rotations to the right and to the left indicating that the calibration of
      vestibular sensory input for spatial orientation did not undergo a directional
      specific control.

PMID- 10076097
TI  - Hemispheric lateralization of the neural encoding of temporal speech features: a
      whole-head magnetencephalography study.
AB  - Using a passive oddball design (randomized series of standard [frequent] and
      deviant [rare] stimuli), the present study investigated the neural encoding of
      syllables differing in a duration parameter (/da/ = short-lag voice onset time
      [VOT], /ta/ = long-lag VOT) by means of whole-head magnetencephalography (MEG).
      Dipolar activities at the level of the supratemporal planes allowed to explain
      the evoked magnetic fields. The N1m/P2m-complex (magnetic equivalent to the N /P2
      wave of the electroencephalogram) in response to standard stimuli showed
      bilateral symmetric distribution. Furthermore, the latency of P2m significantly
      depended on VOT. Finally, the mismatch response to the deviant /da/-syllables
      which represent in German a very frequent word (English: 'here' or 'there')-
      evolved significantly earlier in the left hemisphere as compared to the right
      side. In conclusion, processing speed may be an important aspect of the
      hemispheric specialization of language.

PMID- 10076098
TI  - Brain waves following remembered faces index conscious recollection.
AB  - At a glance, one can often determine whether a face belongs to a known
      individual. To investigate brain mechanisms underlying this memory feat, we
      recorded EEG signals time-locked to face presentations. In the study phase, 40
      unknown faces were presented, 20 of which were accompanied by a voice simulating
      that person speaking. Instructions were to remember the faces with spoken
      biographical information (R-faces) and to forget the others (F-faces). In the
      test phase, famous and non-famous faces were presented in a visually degraded
      manner. Subjects made two-choice fame judgments and priming was observed in the
      form of faster and more accurate responses for old than for new non-famous faces.
      Priming did not differ between R-faces and F-faces. In a second experiment, faces
      were not degraded at test and behavioral responses were made only when faces were
      presented twice in immediate succession. Brain potentials elicited 300 to 900 ms
      after stimulus onset from frontal and parieto-occipital scalp regions were larger
      for R-faces than for F-faces. Recognition tested later was more accurate for R
      faces than for F-faces. Because the study-phase manipulation influenced
      recognition but not priming, we conclude that this procedure succeeded in
      isolating neural correlates of recollective processing from more automatic uses
      of face memory as indexed by priming.

PMID- 10076100
TI  - Re: Dissociated torsional deviation.

PMID- 10076101
TI  - Re: Eagle Jr RC. Laser pointers and color blindness. Ophthalmology 1998; 105:760.

PMID- 10076102
TI  - An efficient treatment and new criteria for cure of strabismic amblyopia: reading
      and Bangerter foils.

PMID- 10076103
TI  - It's time to doctor our approach to vision screening.

PMID- 10076104
TI  - Comment/Critique of the issue 

PMID- 10076105
TI  - The influence of superior oblique anatomy on function and treatment. The 1998
      Bielschowsky Lecture.

PMID- 10076106
TI  - Grand rounds #53: A case of small angle strabismus, torsion, aniseikonia and
      diplopia associated with epiretinal membranes [clincical conference].

PMID- 10076108
TI  - The pathophysiology of advanced heart failure.

PMID- 10076107
TI  - Frequency of silent myocardial ischemia with 12-lead ST segment monitoring in the
      coronary care unit: are there sex-related differences?
AB  - BACKGROUND: Ischemia that occurs in the coronary care unit (CCU), whether
      symptomatic or silent, is associated with significant in-hospital and out-of
      hospital complications. Studies have reported that more than 90% of ischemic
      episodes are silent in patients with unstable angina who are treated in the CCU
      with maximal medical therapy. Prior reports indicate that women complained more
      frequently of chest pain than men did. PURPOSE: The aim of this study was to
      compare the frequency of silent myocardial ischemia in men versus women with use
      of continuous 12-lead ST segment monitoring in the CCU. A secondary goal was to
      determine whether silent ischemia was associated with less ST segment deviation
      as compared with symptomatic ischemia. METHOD: Patients admitted for treatment of
      acute coronary syndrome in the CCU and who subsequently had 1 or more ischemic
      events during their monitoring period were selected for this analysis. All
      patients were continuously monitored (42.5 hours +/- 37.6) in the CCU with the
      EASI (Zymed Medical Instruments, Camarillo, Calif) 12-lead electrocardiogram
      (ECG) system that derives 12 leads with use of 3 information channels and 5
      electrodes. RESULTS: Of 491 patients, 128 (91 men and 37 women) had at least 1
      episode of transient myocardial ischemia. Men and women did not differ in their
      proportion of chest pain during ischemia (men 27% and women 21%, NS). For both
      men and women, ST segment deviation was significantly greater during symptomatic
      ischemia compared with silent ischemia. CONCLUSION: There are no sex-related
      differences in ischemic events in the CCU in regards to the variables of chest
      pain and ST magnitude. Therefore, because chest pain is not a reliable indicator
      of myocardial ischemia in the CCU, regardless of sex, patients should be
      adequately monitored for ischemic events.

PMID- 10076109
TI  - Cost of hospitalizations for heart failure: sodium retention versus other
      decompensating factors.
AB  - OBJECTIVE: To determine the cost of heart failure-related hospital admissions and
      to compare the cost of admissions for sodium retention with the cost of
      admissions for other decompensating factors. DESIGN: Retrospective, non
      experimental, cost analysis. SETTING: Midwestern university-affiliated, tertiary
      care, medical center. SAMPLE: Two hundred seven heart failure-related admissions,
      117 (57%) of which were for sodium retention leading to volume overload. OUTCOME
      MEASURES: Cost of hospitalization. PROCEDURE: Data obtained from the patient and
      financial records of patients hospitalized for heart failure in 1992 were
      analyzed using the ratio of cost-to-charge accounting procedure. RESULTS: The
      total cost was $2,442,720 for the 207 heart failure-related admissions; the
      average cost was $12,400 per admission. Approximately half of the cost of the
      hospitalizations was expended in the 4 cost centers comprising routine and
      critical care services, which incorporate room charges and nursing care. Another
      one third of the cost was for supplies, medications, and laboratory tests.
      Admissions as a result of sodium retention had lower costs than admissions as a
      result of other factors. CONCLUSION: The cost of hospitalization for heart
      failure is high. Routine services, supplies, medications, and laboratory tests
      used by these patients contribute to the high cost of care. Improved outpatient
      management strategies are necessary to reduce hospital admissions as a result of
      sodium retention.

PMID- 10076110
TI  - Thrombosis of mitral valve prosthesis presenting as abdominal pain.
AB  - A 67-year-old woman presented with abdominal pain, anemia, and leukocytosis. Five
      years previously, the patient had undergone mitral valve replacement with a St.
      Jude bileaflet mechanical prosthesis. After her admission, echocardiography
      confirmed an immobile leaflet of the prosthetic valve. At urgent surgery,
      thrombosis and pannus, obstructing the disc, were found, and the mechanical valve
      was replaced with a bioprosthesis. The incidence of mitral valve thrombosis is
      low, ranging from 0.1% to 5.7% per patient per year. Patients who receive
      inadequate anticoagulation, particularly with valve prostheses in the mitral
      position, have an increased risk for thrombus or pannus formation. Presentation
      varies, from symptoms of congestive heart failure or systemic embolization, to
      fever or no symptoms. New or worsening symptoms in a patient with a prosthetic
      heart valve should raise concerns about prosthetic dysfunction. Aggressive
      investigation and, if indicated, urgent or emergency surgery for treatment can be
      lifesaving.

PMID- 10076111
TI  - Intradermal normal saline solution, self-selected music, and insertion difficulty
      effects on intravenous insertion pain.
AB  - OBJECTIVE: To examine the effect of listening to self-selected music versus an
      intradermal injection of normal saline solution on the intensity and distress of
      intravenous (IV) catheter insertion pain. DESIGN: Prospective, randomized,
      controlled study. SETTING: Inpatient and outpatient units in 2 university
      affiliated southwestern medical centers. PATIENTS: One hundred ten adult
      inpatients and outpatients undergoing IV therapy. OUTCOME MEASURES: Pain
      intensity, pain distress, and IV insertion difficulty visual analog scales.
      INTERVENTION: Patients were randomly assigned to receive an intradermal injection
      of normal saline solution, listen with headphones to self-selected music, or be
      in a control group for IV insertion. RESULTS: A MANOVA revealed no statistically
      significant multivariate or univariate differences in pain by treatment group,
      but significantly higher pain distress scores with failed IV insertions. The pain
      intensity and distress scores were significantly higher in the saline solution
      group when compared with the music and control groups combined. Insertion
      difficulty was significantly positively correlated with pain intensity and
      distress for the entire sample, with weak, nonsignificant correlations in the
      music group. CONCLUSION: Intradermal unpreserved saline solution contributes to
      greater pain intensity and distress, greater insertion difficulty, and a higher
      failure rate than the use of music or routine IV insertion. Listening to
      preferred music attenuates the effect of insertion difficulty on IV insertion
      pain. Intravenous insertion attempts were unsuccessful in more than one third of
      the subjects, resulting in higher pain distress scores. Further research is
      needed on interventions to reduce IV insertion pain and on factors contributing
      to IV insertion failure.

PMID- 10076112
TI  - Modifying perfusion, nutrition, and stress to promote wound healing in patients
      with acute wounds.
AB  - Tissue injury is common among patients in acute care settings. The subsequent
      response to injury, wound healing, follows an intricate but well-defined sequence
      that, under normal conditions, proceeds to satisfactory repair. However, because
      of the complexity of the healing response, several factors can intervene to
      impair normal healing. As a better understanding of how diverse factors influence
      healing is gained, the use of interventions that modulate these factors becomes
      possible and potentially beneficial. This article reviews knowledge of perfusion,
      nutrition, and stress as they relate to healing in patients experiencing acute
      wounds. Therapeutic implications based on current research are discussed.

PMID- 10076113
TI  - Stenotrophomonas maltophilia infection and colonization in the intensive care
      units of two community hospitals: A study of 143 patients.
AB  - STUDY OBJECTIVE: To study the epidemiology of Stenotrophomonas maltophilia
      infections in the intensive care units (ICUs) of community general hospitals.
      DESIGN: Retrospective chart review of 143 patients with cultures positive for S.
      maltophilia over a 2-year period. SETTING: Intensive care units of 2 community
      general hospitals. RESULTS: Patients with S. maltophilia infection or
      colonization were elderly (mean age 62.4 years), intubated for a mean of 11.8
      days, and had a mean Acute Physiology and Chronic Health Evaluation II (APACHE
      II) score of 16.6. A tracheostomy was present in 22.4%, and underlying chronic
      respiratory disease and malignancy were found in 25.9% and 15.4%, respectively.
      Only 2 patients (1.4%) were neutropenic. Most isolates (89.5%) were from the
      respiratory tract and were part of a polymicrobial culture in 52. 5% of patients.
      Only a slightly higher APACHE II score (mean = 18.0, SD 7.8 vs mean = 15.6, SD
      6.2, P = 0.052) differentiated patients with infection from those with
      colonization. All but 2 patients were exposed to antibiotics before their
      positive culture. Crude mortality rate was 41.3% overall and was significantly
      higher in those with an APACHE II score of 15 or more (48.8% vs 30.5%, P = 0.
      028). CONCLUSION: S. maltophilia is emerging as an important cause of nosocomial
      infection, especially pneumonia, in ICUs of community general hospitals. Patients
      tend to be elderly, intubated for a mean of about 12 days, have high APACHE II
      scores, and frequently have a tracheostomy or underlying chronic respiratory
      disease. In contrast to earlier reports, neutropenia and underlying malignancy
      are uncommon in our ICU population. We found prior antibiotic exposure was almost
      universal and similar to previous reports, but use of imipenem was much less
      common in our community hospital patients. Patients with a high APACHE II score
      should be considered infected rather than colonized, but differentiation of
      infection from colonization remains problematic. Isolation of S. maltophilia from
      a patient carries a crude mortality rate of 41.3%, and patients with an APACHE II
      score of 15 or more have a significantly higher mortality rate than those with
      lesser scores, approaching 50%. Trimethoprim-sulfamethoxazole (TMP-SMX) remains
      the drug of choice for infections caused by S. maltophilia.

PMID- 10076114
TI  - Respiratory Nursing Society position statement on long-term oxygen therapy.
      Introduction.

PMID- 10076115
TI  - Ochrobactrum anthropi bacteremia.
AB  - Ochrobactrum Anthropi (O. anthropi ), formerly known as Achromobacter CDC group
      Vd, is a gram-negative bacillus that is aerobic, oxidase producing, and
      nonlactose fermenting. This organism has been found in environmental and hospital
      water sources and has pathogenic potential in humans. Most reports in the
      literature of O. anthropi bacteremia are associated with intravenous line
      infections. We describe a case of bacteremia with O. anthropi in a 33-month-old
      boy with acute osteomyelitis. O. anthropi bacteremia also has been reported in
      immunocompromised hosts. Rarely, O. anthropi has been a cause of soft tissue or
      bone infection.

PMID- 10076116
TI  - Pulmonary manifestations of inhaled street drugs.

PMID- 10076117
TI  - Letter 

PMID- 10076118
TI  - Summary of analysis of published articles: January 1 through December 31, 1998.

PMID- 10076119
TI  - Supracervical hysterectomy: back to the future?
AB  - Supracervical hysterectomy, commonly performed in the earlier decades of this
      century, is rarely performed in contemporary practice. The desire to prevent
      future cervical cancer initially underlay the advocacy of total hysterectomy.
      Cervical cytologic screening and effective outpatient treatment of preinvasive
      cervical disease are commonly available. Cancer of the cervical stump is an
      uncommon and largely preventable occurrence. Removal of the normal cervix
      reportedly may have adverse effects on bladder, bowel, and sexual function.
      Reduced operating time and a shorter recovery period may be associated with a
      supracervical procedure. The risk of subsequent cervical cancer may not outweigh
      the benefits of supracervical hysterectomy, which should be offered as an option
      to selected patients. Supracervical hysterectomy by minilaparotomy is within the
      capability of practicing gynecologists and may be adaptable to outpatient short
      stay surgery, offering a cost-effective alternative for a variety of gynecologic
      conditions.

PMID- 10076120
TI  - Restructuring residency training in obstetrics and gynecology.
AB  - This essay presents a brief review of the history advocating a restructuring of
      residency training to increase the flexibility of the experience. The advantages
      for both the general obstetrician-gynecologist and the subspecialist are
      reviewed.

PMID- 10076121
TI  - Recurrence of ovarian endometrioma after laparoscopic excision.
AB  - OBJECTIVE: Our purpose was to evaluate the recurrence rate after laparoscopic
      excision of ovarian endometrioma. STUDY DESIGN: An unrandomized prospective
      clinical study was performed at 2 tertiary-care centers of 366 patients who had a
      minimum of 6 months of postoperative follow-up or 6 months after the suspension
      of medical therapy after laparoscopic ovarian endometrioma excision. Patients
      underwent clinical examination and vaginal ultrasonography 3, 6, and 12 months
      after surgery and subsequently at least once a year. We evaluated the cumulative
      recurrence rate of pain and clinical findings of ovarian endometrioma, the rate
      of repeated surgery, and the recovery of fertility. RESULTS: During follow-up we
      observed ultrasonographic recurrence in 26 (7.1%) cases; surgery was repeated in
      12 (3.3%) cases. The cumulative rate of ultrasonographic recurrence over 48
      months was 11.7%, whereas the cumulative rate of a second surgery was 8.2%.
      Ultrasonographic cyst recurrence was associated with pain recurrence in 73% of
      cases, whereas in the remaining 27% the recurrence was asymptomatic. Significant
      factors related to recurrence of endometriomas would appear to be the stage of
      disease (P =.03) and previous surgery for endometriosis (P =.003). Eighty-five
      (23.2%) women conceived during follow-up. CONCLUSIONS: Laparoscopic treatment of
      endometriomas seems to be both effective and reliable. The rate of recurrence
      appears to be correlated to the duration of follow-up. Stage IV disease and
      previous surgery for endometriosis are unfavorable prognostic factors.

PMID- 10076122
TI  - Vaginal heat shock protein expression in symptom-free women with a history of
      recurrent vulvovaginitis.
AB  - OBJECTIVES: The cause of recurrent vulvovaginitis remains unexplained in most
      cases. Heat shock protein synthesis is induced under conditions of stress; its
      presence in vaginal samples from women who were between episodes of recurrent
      vulvovaginitis thus might reflect a persistent perturbation in the local milieu.
      STUDY DESIGN: We undertook an evaluation by means of enzyme-linked immunosorbent
      assay of 60-kd heat shock protein and inducible 70-kd heat shock protein
      expressions in vaginal wash samples from 24 symptom-free women with a history of
      recurrent vulvovaginitis and 19 matched control subjects. The samples were also
      tested for Candida albicans, Chlamydia trachomatis, Ureaplasma urealyticum,
      Mycoplasma hominis, and human papillomavirus by polymerase chain reaction; for
      bacterial vaginosis by clinical and microbiologic evaluation; and for interleukin
      10, interleukin 1, interleukin 8, RANTES, and eotaxin by enzyme-linked
      immunosorbent assay. RESULTS: The presence of 60-kd heat shock protein was
      detected in 11 women with recurrent vulvovaginitis (45.8%) and 1 control subject
      (5.3%, P =.005). Similarly, 70-kd heat shock protein was present in 8 patients
      with recurrent vulvovaginitis (33.3%) and no control subjects (P =.005). The
      presence of 60-kd heat shock protein and the presence of 70-kd heat shock protein
      were correlated with each other (P =.02), as were both 60-kd heat shock protein
      (P =.006) and 70-kd heat shock protein (P =.01) correlated with IL-10. There was
      no relation between the presence of 60-kd heat shock protein or 70-kd heat shock
      protein and detection of IL-1, IL-8, or any microorganism. CONCLUSION: The
      expression of heat shock proteins and IL-10 in the vaginas of women with a
      history of recurrent vulvovaginitis but not in the vaginas of control subjects
      suggests the existence of differences in the vaginal milieu between the 2 groups,
      even when both are without vaginal symptoms.

PMID- 10076123
TI  - Modification of plasma insulin-like growth factors and binding proteins during
      oral contraceptive use and the normal menstrual cycle.
AB  - OBJECTIVE: Sex steroid regulation of the insulin-like growth factor axis is a
      subject of contention. We examined the effect of combined oral contraceptives and
      investigated the cyclic variations in the insulin-like growth factor axis. STUDY
      DESIGN: Fasting blood samples were taken from 9 women receiving oral
      contraceptives, 10 women receiving no medication, and 10 male subjects. RESULTS:
      In women receiving oral contraceptives, insulin-like growth factor binding
      protein 1 remained highly phosphorylated and levels were acutely increased by sex
      steroid treatment (305 +/- 110 microg/L on day 14 of the cycle [medication phase]
      vs 118 +/- 70 microg/L during the medication-free period, P <.03). In women
      receiving no medication, insulin-like growth factor binding protein 1 levels were
      significantly lower (69 +/- 50 microg/L on day 14 of the menstrual cycle, P
      <.001) and varied cyclically, with a rise in the late-secretory phase that
      coincided with the appearance of nonphosphorylated and less phosphorylated
      insulin-like growth factor binding protein 1 isoforms. Compared with those in
      untreated women and in men, insulin-like growth factor I levels were decreased in
      women receiving oral contraceptives (405 +/- 104 ng/mL in untreated women and 330
      +/- 28 ng/mL in men vs 287 +/- 73 ng/mL in women receiving oral contraceptives, P
      <.004). Oral contraceptive use had no effect on insulin-like growth factor II
      levels, and neither insulin-like growth factor I nor insulin-like growth factor
      II showed cyclic variation. CONCLUSION: The bioavailability of insulin-like
      growth factor I is reduced in users of oral contraceptives. This may contribute
      to the metabolic changes observed in such subjects.

PMID- 10076124
TI  - Prevalence of bone mineral changes during postpartum amenorrhea and after
      resumption of menstruation.
AB  - The prevalence of significant bone loss after a period of amenorrhea and 1-year
      follow-up in a cohort of healthy postpartum women was higher at the femoral neck
      than at the lumbar spine (42% versus 5%). This indicates that reproduction can
      predispose the proximal femur of a considerable proportion of postpartum women to
      permanent bone loss.

PMID- 10076125
TI  - Progestational effects of combinations of gestodene on the postmenopausal
      endometrium during hormone replacement therapy.
AB  - OBJECTIVE: The aim of the study was to assess the dose-response effects on the
      postmenopausal endometrium of 3 sequential combined hormone replacement regimens
      and 1 continuous combined hormone replacement regimen of estradiol and gestodene.
      STUDY DESIGN: In this 2-year double-blind, placebo-controlled study, 278 healthy
      postmenopausal women received either 2 mg estradiol sequentially combined with 50
      microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously
      combined with 25 microg gestodene, or placebo. RESULTS: All 4 hormone treatment
      regimens produced a safe endometrial histologic appearance. The regimens that
      were based on the lower dose of 1 mg estradiol was associated with less uterine
      bleeding than were those that were based on 2 mg estradiol. For sequentially
      opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less
      efficient in producing secretory activity than was the dose of 50 microg
      gestodene. The measurement of placental protein 14 in serum reflected the
      secretory transformation of the endometrial buildup. CONCLUSION: The reduction in
      bleeding episodes associated with regimens with lower estradiol doses may lead to
      improved long-term therapy compliance by menopausal women. The potency of
      progestogens can be assessed by measuring the serum concentration of placental
      protein 14.

PMID- 10076126
TI  - Comparison of fine-needle aspiration cytologic findings of ovarian cysts with
      ovarian histologic findings.
AB  - OBJECTIVE: The purpose of this study was to compare cytologic findings of fluid
      from ovarian cysts with ovarian histologic findings. STUDY DESIGN: Ovaries
      submitted for pathologic examination were grossly examined for ovarian cysts.
      Fluid was removed by needle aspiration from intact ovarian cysts and prepared for
      cytologic examination. The cytologic findings were categorized as benign,
      malignant, indeterminate, and nondiagnostic. Histologic classification was
      assigned using the guidelines established by the World Health Organization. A
      single pathologist evaluated each cytologic specimen and was blinded to the gross
      appearance and histologic findings of each ovary. Cytologic diagnoses were
      compared with the histologic diagnoses. RESULTS: The study material consisted of
      105 ovaries from 98 women. A comparison of the ovarian histologic findings with
      the cytologic diagnosis was performed in 89 of 105 cases. Histologic examination
      of the ovaries revealed 89 benign ovarian tumors and 13 ovarian carcinomas. The
      sensitivity of ovarian cyst cytologic evaluation was 25%, and the specificity was
      90%. The false-positive rate for ovarian cytologic evaluation was 73%, and the
      false-negative rate was 12%. CONCLUSIONS: Cytologic examination of aspirated
      ovarian cyst fluid does not accurately predict ovarian histologic findings.

PMID- 10076127
TI  - Gasless laparoscopic ovarian cystectomy during pregnancy: comparison with
      laparotomy.
AB  - OBJECTIVE: The efficacy and safety of gasless laparoscopic ovarian cystectomy
      during pregnancy were compared with those of conventional laparotomy. STUDY
      DESIGN: Subjects for the 2 study groups were selected from consecutive patients
      who satisfied all entrance criteria. Seventeen women who underwent gasless
      laparoscopic cystectomy were compared with 18 women who underwent cystectomy by
      laparotomy. The intraoperative and postoperative courses, pregnancy outcomes, and
      complications were compared. RESULTS: The patients' ages, body mass indexes, mean
      cyst diameters, fetal gestational ages, and types of cysts did not differ
      significantly between the two groups. Blood loss, analgesic use, and need for
      tocolytic agents were significantly less in the laparoscopy group than in the
      laparotomy group. No abortions or preterm deliveries occurred in the laparoscopy
      group, whereas 1 abortion was recorded in the laparotomy group. CONCLUSION:
      Gasless laparoscopic ovarian cystectomy offers significant advantages with
      respect to laparotomy for the pregnant patient.

PMID- 10076128
TI  - Halofuginone, an inhibitor of collagen type I synthesis, prevents postoperative
      adhesion formation in the rat uterine horn model.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of
      halofuginone-a specific inhibitor of collagen type I synthesis-in preventing
      uterine horn adhesion formation in rats. STUDY DESIGN: Adhesions were induced by
      scraping the rat uterine horns until capillary bleeding occurred. Halofuginone
      was either injected intraperitoneally or administered orally. The number and
      severity of the adhesions were scored. Collagen alpha1(I) gene expression was
      evaluated by in situ hybridization; total collagen was estimated by sirius red
      staining. Collagen synthesis in response to halofuginone was evaluated in cells
      cultured from the adhesions. RESULTS: Regardless of the administration procedure,
      halofuginone reduced significantly the number and severity of the adhesions in a
      dose-dependent manner. Halofuginone prevented the increase in collagen alpha1(I)
      gene expression observed in the rats that underwent this procedure, thus
      affecting only the newly synthesized collagen but not the resident collagen. In
      cells derived from rat uterine horn adhesions, halofuginone induced dose
      dependent inhibition of collagen synthesis. CONCLUSIONS: Upregulation of collagen
      synthesis appears to play a critical role in the pathophysiologic mechanism of
      adhesion formation. Halofuginone could be used as an important means of
      understanding the role of collagen in adhesion formation and might become a novel
      and promising antifibrotic agent for preventing adhesion formation after pelvic
      surgery.

PMID- 10076129
TI  - Human immunodeficiency virus screening among pregnant women in France: results
      from the 1995 National Perinatal Survey.
AB  - OBJECTIVE: The aim of the study was to assess how the French legislation
      requiring physicians to offer human immunodeficiency virus screening routinely at
      the beginning of prenatal care has been implemented and to explore areas in which
      improvement is required. STUDY DESIGN: The survey included all births in France
      during a 7-day period in February 1995. A total of 12,341 women were asked
      whether they knew whether they had undergone a human immunodeficiency virus
      antibody test before or during the pregnancy. Factors that could have influenced
      their knowledge of whether they had been tested were also assessed. RESULTS: Of
      the women questioned, 87.3% stated that they had been tested before or during
      pregnancy, 7.6% said that they had not been tested, and 5.1% stated that they did
      not know whether a test had been performed. Among those who said that they had
      not been tested before the pregnancy in question, 84. 9% reported that they were
      tested during the pregnancy. The multivariate analysis revealed that women from
      North Africa differed significantly from French women in both unawareness of
      screening status and the proportion who reported not being screened (odds ratio
      2.1 with 95% confidence interval 1.6-2.9 and odds ratio 2.4 with 95% confidence
      interval 1.8-3.1, respectively). There was, however, no significant difference
      between women from sub-Saharan Africa and French women in these variables. A
      lower educational level was an important predictor of unawareness of screening
      status (odds ratio 2.6 with 95% confidence interval 2.0-3.4). Associations were
      observed between reporting of unscreened status and low levels of use of prenatal
      care services (<6 prenatal consultations odds ratio 1.3 with 95% confidence
      interval 1.0-1.6, <3 ultrasonographic examinations odds ratio 1.7 with 95%
      confidence interval 1.3-2.0, and no prenatal consultation at the maternity
      hospital odds ratio 1. 5 with 95% confidence interval 1.2-1.8). CONCLUSION: The
      1995 National Perinatal Survey, which appears to indicate extensive human
      immunodeficiency virus screening of pregnant women in France, shows that the
      nonmandatory nature of the French policy of systematically offering prenatal
      human immunodeficiency virus screening has not prevented a high proportion of
      women from learning their screening status. The less comprehensive screening
      among women in certain subgroups suggests that human immunodeficiency virus
      information should be better adapted for these women.

PMID- 10076130
TI  - Risk factors for rapid-onset cervical cancer.
AB  - OBJECTIVES: The current study was designed to elucidate risk factors associated
      with the development of cervical cancer during the course of routine Papanicolaou
      smear screening (rapid-onset cervical cancer). STUDY DESIGN: Four hundred eighty
      three women diagnosed with invasive cervical cancer, representing 73% of all such
      tumors diagnosed in Connecticut between 1985 and 1990, were studied. Papanicolaou
      smear screening and risk factor information was obtained by questionnaire and
      physician record review. Results from human papillomavirus deoxyribonucleic acid
      testing by polymerase chain reaction of tumor samples were available for 278
      study participants. Prediagnostic Papanicolaou smear slides were reviewed for 67%
      of cases with a screening history. Screening history information, slide review,
      and questionnaire data were used to classify women as having rapid-onset cervical
      cancer (n = 43), possible rapid-onset cervical cancer (n = 111), or normal-onset
      cervical cancer (n = 329). RESULTS: Compared with normal-onset cases, rapid-onset
      cases tended to be younger (P =.001) and were more likely to be white (P =.002),
      diagnosed with adenocarcinomas or adenosquamous carcinomas (P =.001), and
      diagnosed with early-stage disease (P =.001). Cases diagnosed as possible rapid
      onset disease tended to have a profile that was intermediate to that observed for
      rapid-onset and normal-onset cases. Human papillomavirus deoxyribonucleic acid
      was detected in 75.2% of cases tested. Compared with women who tested positive
      for human papillomavirus type 16 or other, those positive for human
      papillomavirus type 18 had a relative risk for rapid-onset disease of 1.6 (95%
      confidence interval 0.52-4.9). No significant association was observed between
      type 18 and possible rapid-onset disease when possible rapid-onset cases were
      compared with women diagnosed with normal-onset cervical cancer (relative risk
      0.67, 95% confidence interval 0.29-1.6). Oral contraceptive use, cigarette
      smoking, number of pregnancies, and a maternal history of cervical cancer were
      not significantly associated with rapid-onset disease. CONCLUSIONS: Results from
      this study suggest that the risk factors associated with the development of rapid
      onset cervical cancer are similar to those for normal-onset disease.

PMID- 10076131
TI  - The microbiologic effect of digital cervical examination.
AB  - OBJECTIVE: The purpose of this study was to determine whether digital examination
      introduces vaginal organisms into the cervix. STUDY DESIGN: Thirty-five women
      with reported ruptured membranes at >/=34 weeks' gestation underwent a sterile
      speculum examination and a standardized semiqualitative, semiquantitative
      endocervical culture before and immediately after digital cervical examination.
      RESULTS: Cultures taken before digital examination demonstrated a mean of 2.8 +/-
      1.7 different types of organisms, whereas cultures taken after digital
      examination demonstrated a mean of 4.4 +/- 1.5 different types of organisms (P
      <.0001). Twenty-eight patients (80%) had heavier growth or a greater number of
      different organisms in the postexamination culture than in the pre-examination
      culture. The state of the fetal membranes (ruptured as opposed to intact) did not
      alter these relationships. CONCLUSION: An immediate effect of digital examination
      is the introduction of vaginal organisms into the cervical canal.

PMID- 10076132
TI  - Impact of the fetal fibronectin assay on admissions for preterm labor.
AB  - OBJECTIVE: The aim of the study was to determine whether use of the fetal
      fibronectin assay would decrease the number of admissions to labor and delivery
      for diagnosis and treatment of preterm labor. STUDY DESIGN: A prospective cohort
      design was used to compare preterm labor admissions during a 12-month period of
      fetal fibronectin assay use (study) against a baseline period before fetal
      fibronectin assay was implemented as standard protocol. Patients coming to the
      physician's office or hospital with signs and symptoms of preterm labor had a
      sample obtained for fetal fibronectin assay per labeling criteria. Comparisons
      were made with the Mann-Whitney U test, independent Student t test, chi2 test,
      and Fisher exact test. P <.05 was considered significant. RESULTS: There was no
      difference noted in the number of deliveries between the baseline and study
      years. During the study year 251 of 330 patients evaluated for preterm labor met
      study criteria and had the fetal fibronectin assay completed. Eight patients did
      not have fetal fibronectin assay results available because of specimen handling
      errors, leaving 243 subjects available for study. Compared with the baseline
      year, the study year had significantly fewer admissions for preterm labor,
      preterm labor admissions per patient, and prescriptions written for tocolytic
      agents. In addition, the length of stay per admitted patient was significantly
      reduced. The study population had no differences in neonatal outcomes from the
      baseline population in terms of deliveries at <35.0 weeks' gestation, number of
      admissions to the neonatal intensive care unit, neonatal intensive care unit
      length of stay, or days of ventilatory support per patient admitted to the
      neonatal intensive care unit. CONCLUSIONS: Use of the fetal fibronectin assay
      resulted in significantly reduced preterm labor admissions, length of stay, and
      prescriptions for tocolytic agents. No negative impact on neonatal outcomes was
      observed. Reductions in admissions for preterm labor and in charges per admission
      resulted in approximately $486,000 saved during the study period. A trend toward
      increased corticosteroid administration (for neonates ultimately admitted to the
      neonatal intensive care unit) was noted.

PMID- 10076133
TI  - Increased contents of phospholipids, cholesterol, and lipid peroxides in decidua
      basalis in women with preeclampsia.
AB  - OBJECTIVES: Accelerated recovery from preeclampsia has been reported after
      postpartum curettage. Lipid deposition in decidual spiral arteries (acute
      atherosis) is a histologic feature of preeclampsia. Increased tissue content of
      lipids is associated with enhanced formation of lipid peroxides, which are
      compounds that may induce endothelial dysfunction. We hypothesized that the
      content of lipids and lipid peroxides is elevated in decidua basalis tissues of
      women with preeclampsia compared with those of women with uneventful pregnancies.
      STUDY DESIGN: Decidua basalis tissues were obtained with a vacuum aspiration
      technique during cesarean delivery from 30 preeclamptic and 34 uneventful
      pregnancies. Total cholesterol, phospholipids, triglycerides, free fatty acids,
      and lipid peroxides were quantified. RESULTS: Significantly elevated contents of
      phospholipids, total cholesterol, and lipid peroxides were found in preeclamptic
      decidua basalis tissues, whereas the contents of triglycerides and free fatty
      acids did not differ significantly from those of the control group. CONCLUSIONS:
      Decidua basalis tissues, with their elevated lipid content, may be a source of
      lipid compounds that can cause maternal endothelial dysfunction in preeclampsia.

PMID- 10076134
TI  - Randomized controlled trial of prevention of perineal trauma by perineal massage
      during pregnancy.
AB  - OBJECTIVE: The aim of the study was to evaluate the effectiveness of perineal
      massage during pregnancy for the prevention of perineal trauma at birth. STUDY
      DESIGN: Pregnant women with (n = 493) and without (n = 1034) a previous vaginal
      birth from 5 hospitals in the province of Quebec, Canada, participated in this
      single-blind, randomized, controlled trial. All participants received oral and
      written information on the prevention of perineal trauma. Women in the
      experimental groups were requested to perform a 10-minute perineal massage daily
      from the 34th or 35th week of pregnancy until delivery. RESULTS: Among
      participants without a previous vaginal birth, 24.3% (100/411) from the perineal
      massage group and 15.1% (63/417) from the control group were delivered vaginally
      with an intact perineum, for a 9.2% absolute difference (95% confidence interval
      3.8%-14.6%). The incidence of delivery with an intact perineum increased with
      compliance with regular practice of perineal massage (chi2 for trend 13.2, P =
      0.0003). Among women with a previous vaginal birth, 34.9% (82/235) and 32.4%
      (78/241) in the massage and control groups, respectively, were delivered with an
      intact perineum, for an absolute difference of 2.5% (95% confidence interval 
      6.0% to 11.0%). There were no differences between the groups in the frequency of
      sutured vulvar and vaginal tears, women's sense of control, and satisfaction with
      the delivery experience. CONCLUSION: Perineal massage is an effective approach to
      increasing the chance of delivery with an intact perineum for women with a first
      vaginal delivery but not for women with a previous vaginal birth.

PMID- 10076135
TI  - Effects of blood pressure on orbital and middle cerebral artery resistances in
      healthy pregnant women and women with preeclampsia.
AB  - OBJECTIVE: The object of the study was to test the hypothesis that preeclampsia
      leads to an abnormal vascular response to increasing blood pressure in cerebral
      vessels by analyzing the relationship between mean arterial pressure and
      resistance index in the central retinal, ophthalmic, and middle cerebral arteries
      in women with normal pregnancies and women with preeclampsia. STUDY DESIGN:
      Transcranial and color flow Doppler ultrasonographic studies were used to
      determine systolic, diastolic, and mean velocities and the resistance indexes in
      the central retinal, ophthalmic, and middle cerebral arteries in 24 women with
      normal pregnancies and 18 women with preeclampsia. In each group the relationship
      between the mean arterial pressure and the resistance index was determined for
      each artery by means of linear regression analysis. The Pearson correlation
      coefficients for each mean arterial pressure versus resistance index relationship
      were compared between the groups. In a separate analysis middle cerebral artery
      data obtained from 79 women with preeclampsia (with and without headache) were
      compared with data from the normal pregnancy group and analyzed in terms of the
      relationship between mean arterial pressure and resistance index. RESULTS: The
      resistance index in women with normal pregnancies decreased with increasing mean
      arterial pressure in all 3 vessels studied (ophthalmic artery r = -0.33, central
      retinal artery r = -0. 43, middle cerebral artery r = -0.30). In the women with
      preeclampsia, however, as mean arterial pressure increased the resistance index
      increased in the orbital vessels and decreased in the middle cerebral artery
      (ophthalmic artery r = 0.54, central retinal artery r = 0.65, middle cerebral
      artery r = -0.25). The correlation coefficients in the women with preeclampsia
      were significantly different from those in the women with normal pregnancies for
      the ophthalmic and central retinal arteries (P =. 001) but not for the middle
      cerebral artery (P =.8). Within-group analysis in the patients with normal
      pregnancies showed no differences between the correlation coefficients of the
      studied vessels. In the women with preeclampsia the ophthalmic artery (P =. 02)
      and the central retinal artery (P =.005) were significantly different from the
      middle cerebral artery but not from each other. Women with preeclampsia who had
      headache had a different correlation coefficient for the middle cerebral artery
      than did those without headache (r = -0.34 versus r = 0.23; P <.001). The
      correlation coefficient for the middle cerebral artery for women with
      preeclampsia without headache was not significantly different from the central
      retinal artery and ophthalmic artery correlation coefficients in the general
      preeclampsia group. CONCLUSIONS: Women with preeclampsia demonstrate a different
      relationship between blood pressure and resistance index in the ophthalmic and
      central retinal arteries than do women with normal pregnancies. In the middle
      cerebral artery, however, preeclampsia does not appear to affect the resistance
      index response to increasing mean arterial pressure in women with headache. In
      women with preeclampsia without headache the relationship seen in the ophthalmic
      artery and central retinal artery is preserved in the middle cerebral artery.
      This may indicate a failure in the autoregulatory capacity of the middle cerebral
      artery in the presence of headache. Alternatively, the resistance index response
      in the ophthalmic artery and central retinal artery may represent small-caliber
      vessel vasospasm that is not present in the middle cerebral artery in women with
      preeclampsia who have headache.

PMID- 10076136
TI  - Induction of intrauterine growth restriction with a low-sodium diet fed to
      pregnant rats.
AB  - OBJECTIVE: A low-sodium diet fed to female rats before mating through parturition
      leads to pups of lower weight. We characterized the effect of low dietary sodium
      during the last week of gestation (after fetal organogenesis) on fetal and
      maternal homeostasis. STUDY DESIGN: Pregnant Sprague-Dawley rats were randomly
      assigned to a control group or to a group fed a low-sodium diet from gestational
      days 15 through 22. Systolic blood pressures were measured throughout pregnancy.
      On day 22 plasma volume was measured and blood samples were taken for electrolyte
      and hormonal measurements. Fetal and placental weights were also determined.
      RESULTS: Plasma renin activity and aldosterone level were significantly higher in
      the experimental group than in the control group. Plasma volume was significantly
      lower in pregnant rats receiving a low-sodium than in those receiving a control
      diet. Rats receiving a low-sodium diet had pups of lower weight and length (4.45
      +/- 0.22 g, 3.90 +/- 0.06 cm) than pups of the control group (5.21 +/- 0.12 g,
      4.10 +/- 0.02 cm). Pups born to mothers with low-sodium diets recuperated from
      intrauterine growth restriction by 14 days after birth. CONCLUSION: These data
      indicate that a low-sodium diet given to pregnant rats for the last 7 days of
      gestation leads to reduced plasma volume expansion and fetal growth restriction.
      This could prove to be a simple animal model for studying the relationship
      between maternal plasma volume and fetal growth.

PMID- 10076137
TI  - The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8
      and inhibition of secretory leukocyte protease inhibitor.
AB  - OBJECTIVE: The objective of this study was to investigate regulation of
      inflammatory mediators implicated in cervical ripening and to explore the
      mechanisms by which the clinically effective agent prostaglandin E2 may mediate
      cervical ripening. STUDY DESIGN: Cervical biopsy specimens were taken from
      healthy, nonpregnant women undergoing a hysterectomy for a benign nonmalignant
      condition and were cultured, with treatments in quadruplicate, for 24 hours in
      media supplemented with progesterone, dexamethasone, nitric oxide, interleukin 8,
      and prostaglandin E2. Media were collected and assayed by enzyme-linked
      immunosorbent assay for interleukin 8, secretory leukocyte protease inhibitor,
      and prostaglandin E2. Ethical approval was obtained for this study from the local
      ethics committee. RESULTS: Interleukin 8 release from cervical explants was
      stimulated by prostaglandin E2 and nitric oxide and inhibited by progesterone and
      dexamethasone. Secretory leukocyte protease inhibitor release from cervical
      explants was stimulated by progesterone and inhibited by prostaglandin E2.
      Prostaglandin E2 release from cervical explants was stimulated by nitric oxide.
      CONCLUSION: Complex interactions occur between inflammatory cytokines within the
      cervix; these results further our understanding of the mechanism of cervical
      ripening.

PMID- 10076138
TI  - Role of oxytocin in the initiation of term and preterm labor in rats: changes in
      oxytocin receptor density and plasma oxytocin concentration and the effect of an
      oxytocin antagonist, L-366,509.
AB  - OBJECTIVE: Our purpose was to compare the functional roles of oxytocin in term
      and preterm labor in rats by both biochemical and pharmacologic means. STUDY
      DESIGN: We determined the myometrial oxytocin receptor density and the maternal
      plasma concentrations of oxytocin and progesterone on gestational days 18, 20,
      and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with
      labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm
      labor induced by the combined use of bilateral ovariectomy and estradiol
      injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on
      the initiation of both term and preterm labor. RESULTS: The number of tritiated
      oxytocin binding sites in myometrial membranes rapidly increased on gestational
      day 22 (morning) in rats with term labor. Plasma progesterone level decreased in
      an inverse fashion. A rapid increase in circulating oxytocin concentration was
      observed at the onset of delivery in rats in labor at term. Both the plasma
      oxytocin concentration and the receptor density had the same values in rats with
      preterm labor as in rats with term labor. L-366,509 delayed the initiation of
      labor in rats with term and preterm labor in a dose-dependent manner. CONCLUSION:
      It is confirmed biochemically and pharmacologically that oxytocin plays an
      important role in the initiation of both term and preterm labor in rats. The
      oxytocin antagonist examined was able to delay term and preterm labor, so it
      might prove useful in clinical practice for the treatment of preterm labor.

PMID- 10076139
TI  - Induction of labor and the relationship to cesarean delivery: A review of 7001
      consecutive inductions.
AB  - OBJECTIVE: The goal of this project was to study the increasing risk of induction
      of labor in a community hospital and to determine whether it had an adverse
      effect on the rate of cesarean delivery. STUDY DESIGN: From January 1, 1990,
      through July 31, 1997, 18,055 consecutive singleton pregnancies in women who were
      candidates for labor were reviewed via a comprehensive perinatal database. The
      risk of and indication for induction were reviewed. Cesarean delivery rates were
      calculated for nulliparous and multiparous patients by indication for induction
      and were compared with rates for patients who had spontaneous labor. Overall
      trends in cesarean delivery were reviewed for the duration of the study period.
      RESULTS: The annual induction rate significantly rose from 32% to 43% at the
      conclusion of the study period. Labor was induced in nearly 40% of nulliparous
      patients. Postdate pregnancy was the most common indication for induction,
      although few patients were at or beyond 42 weeks' gestation. The cesarean
      delivery rate remained at or below 20% for the years of the study. No increase
      was noted in spite of the increasing risk of induction. However, for nulliparous
      patients who had elective induction of labor, the risk of cesarean delivery was
      twice that of nulliparous patients who had spontaneous labor. CONCLUSION: The use
      of induction methods has significantly increased in this community hospital. More
      than 40% of patients are now candidates for induction. The cesarean delivery rate
      remains low in this facility in spite of a marked increase in risk of operative
      delivery for nulliparous patients who undergo induction.

PMID- 10076140
TI  - Ultrasonographic measurement of liver length in the small-for-gestational-age
      fetus.
AB  - OBJECTIVE: Our purpose was to measure fetal liver size in small-for-gestational
      age fetuses diagnosed by ultrasonography and to determine whether the small
      abdominal circumference used to diagnose small for gestational age is the result
      of a small liver. STUDY DESIGN: Ninety-eight pregnant women who were diagnosed as
      having a fetus that was small for gestational age were included. All had a fetal
      ultrasonographic measurement of abdominal circumference <10th percentile for
      gestational age. Measurements were made of the length of the right lobe of the
      fetal liver within 2 weeks of delivery. The liver length measurements were
      compared with data collected from a normal population that had been previously
      published by the authors. The group of fetuses with liver length measurements
      <10th percentile for gestational age were compared with those with liver length
      measurements within normal limits. RESULTS: Liver length measurements were >10th
      percentile in 80 fetuses (82%). Eighteen fetuses (18%) had small liver lengths,
      and this group had significantly smaller antenatal ultrasonographic measurements
      of head, abdomen, and femur. They were smaller at birth with smaller placentas
      and they had a higher perinatal mortality rate. CONCLUSION: The small abdominal
      circumference measurement that is the mainstay of ultrasonographic diagnosis of
      small for gestational age is thought to be a reflection of fetal liver size. This
      study questions that assumption. The majority of small-for-gestational-age
      fetuses in this small study did not have small liver lengths. The small abdominal
      circumference measurement may reflect a reduction in size of other intra
      abdominal organs, reduced amounts of fat, or possibly an elevated diaphragm
      because of poor lung growth.

PMID- 10076141
TI  - Cervical length in uncomplicated pregnancy: A study of sociodemographic
      predictors of cervical changes across gestation.
AB  - OBJECTIVE: We conducted this study to evaluate sociodemographic factors
      associated with changes in the length of the cervix across gestation in
      pregnancies that resulted in term deliveries. STUDY DESIGN: This study is an
      observational cohort design of sonographically determined cervical length
      measured at 3- to 4-week intervals in 125 women with a singleton pregnancy
      between 20 and 32 weeks gestation. We developed a structured questionnaire to
      collect psychosocial and sociodemographic characteristics. We used bivariate
      analysis, analysis of variance, and regression analysis to study variation in
      cervical length. RESULTS: Overall, cervical length decreased minimally as
      gestational age progressed. However, among black women cervical length decreased
      significantly with increasing gestational age (P =.006). In addition, high
      psychosocial stress was associated with significantly shorter cervices later in
      gestation, independent of race (P =.003). Finally, women whose occupations
      involved skilled manual labor had shorter cervices (P =.02). CONCLUSIONS: Women
      who are black, under stress, or working as skilled manual laborers demonstrate
      significant shortening of the cervix during gestation. Given that a shorter
      cervix predisposes to preterm delivery, our findings provide new insights into
      the well-described association of these psychosocial and sociodemographic factors
      with an increased risk of preterm delivery.

PMID- 10076142
TI  - Perinatal management of women with immune thrombocytopenic purpura: survey of
      United States perinatologists.
AB  - OBJECTIVE: The aim of the study was to determine how perinatologists in the
      United States manage the care of women with immune thrombocytopenic purpura with
      respect to mode of delivery. STUDY DESIGN: US members of the Society of Perinatal
      Obstetricians were surveyed with a 4-question questionnaire. Two mailings were
      sent. Questions 1 and 2 asked for a response regarding the perinatal management
      of delivery for women with chronic immune thrombocytopenic purpura and new-onset
      disease. The options were cordocentesis or fetal scalp blood sampling and
      cesarean delivery if the platelet count was <50,000 cells/microL, cesarean
      delivery if the maternal platelet count was <50,000 cells/microL, cesarean
      delivery of all women with immune thrombocytopenic purpura, and trial of labor
      without determining fetal platelet count. The third question asked for an opinion
      on whether cesarean delivery was protective against intracranial hemorrhage in
      cases of immune thrombocytopenic purpura. The fourth question asked whether the
      practitioner was in academic or private practice or both. RESULTS: Among the 1596
      perinatologists surveyed, there were 940 informative responses (58.9%). Most
      would allow a trial of labor for women with chronic (59.0%) or new-onset (66.6%)
      immune thrombocytopenic purpura. In cases of chronic immune thrombocytopenic
      purpura, 31.0% of those responding would perform an invasive procedure to
      determine fetal platelet count, followed by cesarean delivery if this count was
      <50, 000 cells/microL. In cases of new-onset immune thrombocytopenic purpura,
      25.4% would do so. Of the respondents, 11.8% reportedly considered cesarean
      delivery protective against intracranial hemorrhage, whereas 56.6% did not and
      31.6% were unsure. CONCLUSIONS: The management of women with immune
      thrombocytopenic purpura remains controversial in the United States.
      Approximately two thirds of perinatologists would allow a trial of labor without
      a procedure to determine fetal platelet count. Most physicians surveyed did not
      consider cesarean delivery to be protective against intracranial hemorrhage.

PMID- 10076143
TI  - Reactivities to serotonin and histamine in umbilical and placental vessels during
      the third trimester after normotensive pregnancies and pregnancies complicated by
      preeclampsia.
AB  - OBJECTIVE: The aim of the study was to evaluate responses of umbilical and
      placental arteries and veins to serotonin and histamine after normotensive
      pregnancies and pregnancies complicated by preeclampsia. STUDY DESIGN: Each pair
      of placentas from a normotensive woman and a woman with preeclampsia was matched
      for gestational age. Rings of these vessels were prepared and mounted in tissue
      baths under their respective optimal passive tension. Cumulative concentration
      response curves to serotonin and histamine were measured. RESULTS: Responses to
      serotonin were decreased in umbilical vessels from the preeclampsia group with
      respect to the normotensive group. This is reflected by reduced maximum responses
      and sensitivity (negative logarithm of the 50% effective concentration) to
      serotonin. Maximum response to serotonin was significantly decreased in placental
      vein rings from the preeclampsia group. We recorded a decreased maximal response
      to histamine in placental vein rings from pregnancies complicated by preeclampsia
      with respect to those from normal pregnancies. Among normotensive women there was
      a significant positive linear relationship between neonatal weight and
      sensitivity to serotonin in umbilical and placental veins. This relationship was
      totally absent in preeclampsia. Sensitivity to histamine was linearly related to
      neonatal weight in umbilical vessels of the pooled results of both experimental
      groups. CONCLUSION: The vasoconstrictive effects of serotonin, but not those of
      histamine, are decreased in umbilical and placental vessels after preeclampsia.
      Sensitivities to serotonin and histamine change in umbilicoplacental vessels
      during the third trimester. Altered reactivity to serotonin may play a
      significant role in the reduction of umbilicoplacental blood flow in
      preeclampsia.

PMID- 10076144
TI  - Changes in homocysteine levels during normal pregnancy.
AB  - OBJECTIVE: The objective of this study was to determine the changes in total
      plasma homocysteine concentration that occur during normal pregnancy. STUDY
      DESIGN: In this cross-sectional study homocysteine was measured in 155 normal
      women in the first, second, and third trimesters and in nonpregnant controls. In
      addition, albumin, serum B12, serum folate, and red blood cell folate
      concentrations were measured and correlated to homocysteine values. RESULTS: The
      mean homocysteine concentration (in micromoles per liter) was 5.6 (95% confidence
      interval 3.9-7.3) at 8-16 weeks' gestation, 4.3 (95% confidence interval 3.5-5.3)
      at 20-28 weeks' gestation, 5.5 (95% confidence interval 3.3-7.5) at 36-42 weeks'
      gestation, and 7.9 (95% confidence interval 6.2-9.6) in the nonpregnant control
      group. Homocysteine was significantly lower in all 3 trimesters of pregnancy
      compared with nonpregnant controls (P <.001). Homocysteine levels were directly
      correlated with albumin levels, which decreased during pregnancy. Homocysteine
      concentrations were decreased in subjects taking folic acid supplementation.
      CONCLUSION: Serum concentrations of homocysteine decrease during pregnancy. This
      occurs in association with the physiologic fall in albumin during pregnancy, as
      well as with folic acid supplementation.

PMID- 10076145
TI  - Obstetric determinants of neonatal survival: antenatal predictors of neonatal
      survival and morbidity in extremely low birth weight infants.
AB  - OBJECTIVE: The aim of the study was to compare clinical and ultrasonographic
      variables obtained before delivery as predictors of neonatal survival and
      morbidity in infants weighing </=1000 g at birth. STUDY DESIGN: Maternal data
      available before the birth of singleton infants with birth weights </=1000 g who
      were delivered at the 11 tertiary perinatal centers of the National Institute of
      Child Health and Human Development Network of Maternal-Fetal Medicine Research
      Units were studied. Births that followed extramural delivery, antepartum
      stillbirths, multiple gestations, induced abortions, infants with major
      malformations, and fetuses delivered at <20 weeks' gestation were excluded.
      Ultrasonographic variables, including estimated fetal weight, obstetrically
      estimated gestational age, femur length, and biparietal diameter, and clinical
      variables, such as maternal race, antenatal care, substance abuse, medical
      treatment, reason for delivery, fetal gender, and presentation, were studied with
      logistic regression as predictors of neonatal outcome, including intrapartum
      stillbirth, neonatal death, and survival to 120 days after birth or to discharge
      from the hospital with or without the presence of markers of major morbidity.
      RESULTS: Eight hundred eight infants met enrollment criteria; 63 were excluded
      because of incomplete data and 32 were excluded because of malformations, leaving
      713 for analysis, 386 of whom had an ultrasonographic examination within 3 days
      of delivery that recorded femur length, biparietal diameter, and estimated fetal
      weight. Forty-two percent of births were the result of preterm labor, 22% were
      the result of preterm ruptured membranes, 12% were the result of preeclampsia or
      eclampsia, 9% were the result of fetal distress, 4% were the result of placenta
      previa or abruptio placentae, and 2% were the result of intrauterine growth
      restriction. Perinatal mortality before 24 weeks' gestation exceeded 81% (19%
      stillbirths and 62% neonatal deaths) but declined sharply thereafter. Most
      survivors born before 26 weeks' gestation had serious morbidity. Fetal femur
      length and estimated gestational age predicted survival better than did
      biparietal diameter or estimated fetal weight. Infants who survived with markers
      of serious long-term morbidity could not be distinguished from those who survived
      without morbidity markers before delivery by ultrasonography or clinical data.
      Threshold values for ultrasonographic measurements of biparietal diameter and
      femur length were developed to distinguish fetuses with no chance of survival.
      CONCLUSION: Ultrasonographic assessment of either fetal femur length or
      gestational age predicts neonatal mortality better than do other antenatal tests.
      No tests accurately predicted neonatal morbidity in infants weighing </=1000 g at
      birth.

PMID- 10076146
TI  - Double-blind comparison of carbetocin versus oxytocin in prevention of uterine
      atony after cesarean section.
AB  - OBJECTIVE: The goal of this study was to compare carbetocin, a long-acting
      oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean
      section. STUDY DESIGN: We enrolled 694 patients undergoing elective cesarean
      section in a Canadian multicenter, double-blind, randomized clinical trial. We
      compared the effect of a single 100 microg dose of carbetocin with that of a
      standard 8-hour infusion of oxytocin. The primary outcome was the proportion of
      patients requiring additional oxytocic intervention for uterine atony. A variable
      sample size, sequential design was used. RESULTS: The overall oxytocic
      intervention rate was 7.4%. The odds of treatment failure requiring oxytocic
      intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the
      oxytocin group compared with the carbetocin group, respectively, 32 of 318
      (10.1%) versus 15 of 317 (4.7%), P <.05. CONCLUSIONS: Carbetocin, a new drug for
      the prevention of uterine atony, appears to be more effective than a continuous
      infusion of oxytocin and has a similar safety profile.

PMID- 10076147
TI  - Benefits of maternal corticosteroid therapy in infants weighing </=1000 grams at
      birth after preterm rupture of the amnion.
AB  - OBJECTIVE: The aim of the study was to determine the effects of antenatal
      maternal corticosteroid treatment on selected neonatal outcomes in infants
      weighing </=1000 g at birth after preterm rupture of membranes. STUDY DESIGN: In
      a 1-year (1992-1993) prospective observational study, the National Institute of
      Child Health and Human Development Maternal-Fetal Medicine Units Network
      collected outcome data for 766 infants who did not have a major fetal anomaly and
      who had a birth weight </=1000 g (378 were born after preterm rupture of
      membranes). Only fetuses deemed potentially viable by the obstetrician were
      included in our analysis. Selected neonatal outcomes were compared between
      mothers who did and did not receive antenatal corticosteroids. Logistic
      regression variables included birth weight, sex, race, amnionitis, tocolytic
      therapies, mode of delivery, and surfactant use. RESULTS: Two hundred fourteen of
      the 378 infants whose mothers had preterm rupture of membranes were deemed
      potentially viable; 62 of these mothers received antenatal steroids and 152 did
      not. Groups were similar with respect to gestational age, birth weight, race,
      amnionitis, and delivery mode. Women who received antenatal steroids were more
      likely to have received tocolysis (P <.001). Univariate and regression analyses
      controlling for multiple confounders confirmed no neonatal benefits of maternal
      corticosteroid use. CONCLUSIONS: Corticosteroid treatment in women with preterm
      rupture of membranes was of no apparent benefit to neonates weighing </=1000 g.

PMID- 10076148
TI  - Indicated versus spontaneous preterm delivery: An evaluation of neonatal
      morbidity among infants weighing </=1000 grams at birth.
AB  - OBJECTIVE: The aim of the study was to determine whether infants weighing </=1000
      g after birth who are born to women who undergo indicated preterm delivery have
      different neonatal outcomes than do those born as a result of either spontaneous
      preterm labor or preterm premature rupture of membranes. STUDY DESIGN: In a 1
      year observational study (1992-1993) the National Institute of Child Health and
      Human Development Maternal-Fetal Medicine Units Network collected outcome data
      for 799 infants whose birth weights were </=1000 g. Only singleton infants with
      gestational age >20 weeks who were not produced as the result of an induced
      abortion were included. Our analysis was further limited to infants without major
      congenital anomalies who survived >2 days, were deemed potentially viable by the
      obstetrician, and would have undergone a cesarean delivery for fetal indications
      (N = 411). The primary reason for delivery was categorized as indicated delivery,
      spontaneous preterm labor, or spontaneous preterm premature rupture of membranes.
      Selected neonatal outcomes were evaluated among infants born to women in each of
      these groups. Logistic regression analyses were used to control for the effects
      of other potentially confounding variables. RESULTS: A total of 156 of the 411
      infants were born to women who underwent an indicated preterm delivery, whereas
      160 were born after spontaneous preterm labor and 95 were delivered after preterm
      premature rupture of membranes. Univariate analyses revealed significantly lower
      incidences of grade III or IV intraventricular hemorrhage, grade III or IV
      retinopathy of prematurity, and seizure activity among infants born in an
      indicated preterm delivery than among those born after spontaneous preterm labor
      or preterm premature rupture of membranes. However, infants of women who
      underwent indicated preterm delivery had a more advanced mean gestational age at
      birth than did those born after spontaneous preterm labor or preterm premature
      rupture of membranes (28 +/- 2 weeks, 26 +/- 2 weeks, and 26 +/- 1 weeks,
      respectively, P <.001). Multiple logistic regression analysis was therefore used
      to control for the disparity in gestational age. Multivariate analyses did not
      confirm the apparent improvement in neonatal outcome in the indicated delivery
      group. CONCLUSION: In this population of infants weighing </=1000 g, selected
      neonatal outcomes did not differ according to birth by indicated preterm
      delivery, spontaneous preterm labor, or preterm premature rupture of membranes.

PMID- 10076149
TI  - In vitro modulation of the expression of 15-hydroxy-prostaglandin dehydrogenase
      by trophoblast differentiation.
AB  - OBJECTIVE: Our goal was to determine the expression and activity of 15-hydroxy
      prostaglandin dehydrogenase, a prostaglandin-metabolizing enzyme, in
      differentiating trophoblasts in vitro. STUDY DESIGN: Cytotrophoblasts from
      placentas of term healthy women were cultured in either Ham's-Waymouth medium,
      which hinders the process of cytotrophoblast differentiation, or medium 199,
      which facilitates differentiation into syncytiotrophoblasts. 15-Hydroxy
      prostaglandin dehydrogenase expression was determined with Western
      immunoblotting, and activity was measured by a specific enzyme immunoassay of 13,
      14-dihydro-15-keto prostaglandin F2 alpha, an inactive product of 15-hydroxy
      prostaglandin dehydrogenase activity. RESULTS: The expression and activity of 15
      hydroxy-prostaglandin dehydrogenase were enhanced during trophoblast
      differentiation and were higher in cells grown in medium 199 than in those grown
      in Ham's-Waymouth medium. 8-Bromo-cyclic adenosine monophosphate, which
      stimulates prostaglandin H synthase-2 expression, diminished the expression and
      activity of 15-hydroxy-prostaglandin dehydrogenase in concentration- and time
      dependent manners. CONCLUSIONS: 15-Hydroxy-prostaglandin dehydrogenase expression
      and activity are regulated during trophoblast differentiation and by cyclic
      adenosine monophosphate. Coordinated expression of l5-hydroxy-prostaglandin
      dehydrogenase and prostaglandin H synthase-2 contributes to the regulation of
      prostaglandin release from trophoblasts.

PMID- 10076150
TI  - Simultaneous quantitation from infrared spectra of glucose concentrations,
      lactate concentrations, and lecithin/sphingomyelin ratios in amniotic fluid.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of using
      infrared spectroscopy to simultaneously predict preterm infection, fetal
      distress, and fetal lung maturity. STUDY DESIGN: A total of 189 infrared spectra
      were acquired from amniotic fluid obtained by amniocentesis. The concentrations
      of glucose and lactate and the lecithin/sphingomyelin ratios were determined
      separately by accepted clinical chemistry methods for each sample. Infrared
      spectra were recorded with a commercial spectrometer and 35 microL amniotic fluid
      was used for each spectrum. Calibration models (partial least squares) were
      derived from the correlation between 102 infrared spectra and clinical standard
      analyses; the model was then validated with the remaining 87 spectra. RESULTS: By
      means of the multivariate technique of partial least squares regression,
      calibration models for glucose and lactate were developed that had excellent
      correlation coefficients (r = 0.97 for glucose and r = 0. 91 for lactate); the
      SEs of calibration were 0.04 mmol/L for glucose and 0.09 mmol/L for lactate. The
      validation sets for the quantitation of glucose and lactate predicted by the
      calibration models also yielded good outcomes (r = 0.95 for glucose and r = 0.71
      for lactate, with SEs of prediction of 0.06 mmol/L and 0.18 mmol/L,
      respectively). CONCLUSION: Infrared spectroscopy has the potential to become the
      clinical method of choice for simultaneously predicting preterm infection, fetal
      distress, and fetal lung maturity.

PMID- 10076151
TI  - Amniotic fluid composition in the fetal lamb with intrauterine growth
      restriction.
AB  - OBJECTIVE: Our aim was to examine changes from normal in the composition of
      amniotic fluid in fetal lambs with mild and severe hypoxemia and intrauterine
      growth restriction. STUDY DESIGN: Pregnant sheep underwent maternal
      catheterization at 88 to 93 days' gestation and fetal catheterization at 105-112
      days' gestation. Twelve pregnancies (group 1) provided control data (fetal PaO 2
      18-22 mm Hg), in 12 fetuses (group 2) mild hypoxemia (PaO 2 16-19 mm Hg) was
      induced by prevention of the normal expansion of maternal blood volume, and in 7
      fetuses (group 3) chronic hypoxemia (PaO 2 12-18 mm Hg) developed spontaneously.
      RESULTS: In group 2 amniotic fluid osmolality and sodium concentrations were
      lower (approximately 30 mOsm/kg and 10 mEq/L, P <.05) and urea nitrogen level was
      higher (10 mg/dL, P <.05) than in group 1. In group 3 osmolality and sodium
      concentrations at approximately 120 days' gestation were similar to those in
      group 1. Whereas these values decreased with gestation in groups 1 and 2 (P
      <.05), they remained unchanged or increased in all fetuses in group 3. Mortality
      rates in groups 1, 2, and 3 were 1 of 12, 4 of 12 (difference not significant),
      and 5 of 7 (P <.05), respectively. CONCLUSION: Absence of normal decrease in
      amniotic fluid osmolality with gestation, in association with a high perinatal
      mortality rate, was found in severely but not in mildly hypoxemic fetuses with
      intrauterine growth restriction.

PMID- 10076152
TI  - Maternal Lyme disease and congenital heart disease: A case-control study in an
      endemic area.
AB  - OBJECTIVE: The purpose of this study was to determine whether maternal Lyme
      disease increases the risk of congenital heart defect. STUDY DESIGN: This
      retrospective case-control study was carried out at a medical center in a
      suburban area where Lyme disease is endemic. Case patients comprised 796 children
      with a diagnosis of congenital cardiac anomaly. Control subjects comprised 704
      children without cardiac defects selected from the records of the same pediatric
      cardiology service. Maternal histories were obtained through a mailed
      questionnaire survey. Unconditional logistic regression analyses examined the
      relationship between a history of preconception and prenatal clinical Lyme
      disease or tick bite and case or control status. RESULTS: There was no
      association between congenital heart defect and maternal tick bite (adjusted odds
      ratio 1.1, 95% confidence interval 0.5-2.5) or maternal Lyme disease within 3
      months of conception or during pregnancy (adjusted odds ratio 0.9; 95% confidence
      interval 0.2-3.6). CONCLUSION: A woman who has been bitten by a tick or is
      treated for Lyme disease during or before pregnancy is not at increased risk for
      giving birth to a child with a congenital heart defect.

PMID- 10076153
TI  - Endoscopic laser surgery versus serial amniocenteses in the treatment of severe
      twin-twin transfusion syndrome.
AB  - OBJECTIVE: Severe twin-twin transfusion can be treated by either serial
      amniocenteses with removal of large volumes of amniotic fluid or by endoscopic
      laser coagulation of the communicating vessels. We investigated the benefit of
      laser surgery in comparison to serial amniocenteses in terms of pregnancy
      outcome. STUDY DESIGN: The data used in this comparative study were collected
      from 116 patients with severe twin-twin transfusion syndrome between 17 and 25
      weeks' gestation. The patients were grouped according to the treatment center.
      The first group comprised 73 patients (median gestational age 20.7 weeks) treated
      in Hamburg by fetoscopic laser coagulation of the vascular placental anastomoses
      between January 1995 and May 1997. The second group comprised 43 patients (median
      gestational age 20.4 weeks), fulfilling identical diagnostic criteria and treated
      in Bonn by serial amniocenteses between 1992 and 1996. RESULTS: The overall fetal
      survival rate was not significantly different (61%, 89/146, vs 51%, 44/86; P
      =.239). There was a significantly higher proportion of pregnancies with >/=1
      survivor in the laser-treated group (79%, 58/73, vs 60%, 26/43; P =.033). The
      number of cases with spontaneous intrauterine fetal death of both fetuses was
      significantly lower in the laser-treated group (3%, 2/73, vs 19%, 8/43; P =.003).
      The incidence of abnormal ultrasonographic findings in the brain was
      significantly lower among surviving neonates after laser surgery than after
      amniocenteses (6%, 5/89, vs 18%, 8/44; P =. 03). For pregnancies with >/=1 live
      born baby, a significantly longer interval between first intervention and
      delivery (median 90 vs 72 days, P =.022) leading to a significantly higher
      gestational age at delivery (median 33.7 vs 30.7 weeks, P =.018) was observed for
      the laser-treated group. The birth weights of the donor fetuses were
      significantly higher in the laser-treated group (median 1750 vs 1145 g, P =.034),
      and a trend toward higher birth weight was also found for recipient fetuses
      (median 2000 vs 1560 g, P =.076). CONCLUSIONS: These findings indicate that
      endoscopic laser coagulation of placental vascular anastomoses offers a more
      effective alternative to serial amniocenteses as a treatment of severe second
      trimester twin-twin transfusion syndrome.

PMID- 10076154
TI  - Pretreatment with magnesium sulfate protects against hypoxic-ischemic brain
      injury but postasphyxial treatment worsens brain damage in seven-day-old rats.
AB  - OBJECTIVE: Our purpose was to study the neuroprotective effect of magnesium
      sulfate on hypoxicischemic brain damage and how the timing of magnesium
      administration changes its effect in the newborn rat. STUDY DESIGN: Seven-day-old
      rats (n = 91) were exposed to unilateral carotid artery ligation followed by 2
      hours of hypoxia (8% oxygen in 92% nitrogen). Magnesium sulfate (270 mg/kg) was
      intraperitoneally administered 30 minutes before (pretreatment) or 30 minutes
      after (posttreatment) the 2 hours of hypoxia. In each experiment equivalent
      amounts of saline solution were administered as controls. Seven days after the
      injury the rats were killed and the brains were removed for histologic study with
      hematoxylin and eosin staining. The severity of brain atrophy and neuronal damage
      was evaluated in the cerebral cortex and hippocampus and compared by chi2 test
      between the magnesium group and the controls. RESULTS: Ionized magnesium
      concentrations were significantly increased from 0.52 +/- 0.02 mmol/L to 1.38 +/-
      0.07 mmol/L at 0.5 hour after injection and thereafter gradually decreased to
      0.73 +/- 0.07 mmol/L at 3.5 hours. Magnesium significantly reduced the incidence
      of weight loss (0% in magnesium vs 29% in controls) and protected the cerebral
      cortex from neuronal loss (the incidence of normal, mild, moderate, and severe
      neuronal loss was 48%, 29%, 5%, and 19% in magnesium and 30%, 5%, 25%, and 40% in
      controls, respectively) in the pretreatment group. In the posttreatment group
      magnesium caused increased neuronal damage compared with the controls.
      CONCLUSION: Magnesium sulfate has neuroprotective effects against hypoxia
      ischemia. This effect is restricted to the pretreatment group in which magnesium
      sulfate is administered before the insult.

PMID- 10076155
TI  - Maternal plasma leptin is increased in preeclampsia and positively correlates
      with fetal cord concentration.
AB  - OBJECTIVE: We tested the hypothesis that the maternal leptin concentration would
      be increased in preeclampsia, independent of maternal obesity. STUDY DESIGN:
      Maternal and cord plasma leptin concentrations were compared in 2 groups of women
      with either preeclampsia (n = 24) or normal pregnancy (n = 24), matched 1:1 for
      prepregnancy body mass index and fetal gestational age at sampling. RESULTS:
      Median leptin concentrations were significantly higher (P <. 03) in women with
      preeclampsia (45.6 ng/mL) than in normal pregnant women (27.0 ng/mL) and fell
      rapidly shortly after delivery (26.7 ng/mL and 25.4 ng/mL, respectively). Cord
      leptin was not significantly different between groups (5.4 ng/mL and 5.8 ng/mL,
      respectively). Maternal and cord leptin correlated significantly (rho = 0.76, P
      <.01) only in preeclampsia. CONCLUSION: Preeclampsia is associated with an
      increase in maternal plasma leptin concentrations that strongly correlates with
      the fetal cord concentration at delivery.

PMID- 10076156
TI  - Maternal and neonatal phytoestrogens in Japanese women during birth.
AB  - OBJECTIVE: High levels of soy isoflavonoids among adult Japanese persons are
      associated with a low incidence of hormone-dependent cancers, but nothing is
      known about isoflavonoids in pregnancy. STUDY DESIGN: We studied 7 young healthy
      Japanese women at delivery by measuring 6 phytoestrogen metabolites in maternal
      and cord plasma and in amniotic fluid. RESULTS: Total maternal plasma
      isoflavonoid concentrations ranged from 19 to 744 nmol/L (mean 232 nmol/L), cord
      plasma values ranged from 58 to 831 nmol/L (mean 299 nmol/L), and amniotic fluid
      values ranged from 52 to 779 nmol/L (mean 223 nmol/L). Maternal and cord plasma
      and amniotic fluid lignan values were low. CONCLUSIONS: The high levels of
      isoflavonoid phytoestrogens found in healthy neonatal Japanese infants indicate
      transfer of isoflavonoids from the maternal to the fetal compartment. These
      compounds may modify estrogen metabolism and action during fetal life and perhaps
      affect cancer risk.

PMID- 10076157
TI  - Changes in prostacyclin synthase in pregnant sheep myometrium, endometrium, and
      placenta at spontaneous term labor and regulation by estradiol and progesterone.
AB  - OBJECTIVE: Our purpose was to investigate, first, whether there were changes in
      the abundance of prostacyclin synthase protein in intrauterine tissues of
      pregnant ewes in association with spontaneous term labor. Second, we examined the
      effect of either estradiol or progesterone, or both, on regulation of
      prostacyclin synthase protein abundance in uterine tissues using an
      ovariectomized nonpregnant sheep model. STUDY DESIGN: The abundance of
      prostacyclin synthase protein was quantified by Western blot analysis in the
      myometrium, endometrium, and placenta of pregnant ewes in spontaneous term labor
      (n = 6) and term control ewes not in labor (n = 6). The changes of prostacyclin
      synthase in the myometrium and endometrium of 20 ovariectomized nonpregnant sheep
      (n = 5 for each group) were evaluated after treatment with estradiol,
      progesterone, or both. RESULTS: Prostacyclin synthase protein was present in
      pregnant and nonpregnant sheep myometrium, endometrium, and placenta at a
      molecular weight of about 55 kd. At spontaneous term labor the level of
      prostacyclin synthase decreased in endometrium (P <.05), increased in myometrium
      (P <.05), and remained unchanged in placenta. Estradiol and progesterone had no
      effect on prostacyclin synthase protein abundance in nonpregnant ovine
      endometrium and myometrium. CONCLUSIONS: The decrease in prostacyclin synthase in
      pregnant sheep endometrium during labor may indicate paracrine interactions
      between the endometrium, the myometrium, fetal membranes, or a combination of
      these. The significant increase of prostacyclin synthase in pregnant sheep
      myometrium at spontaneous term labor may contribute to the increased uterine
      sensitivity to oxytocin or stimulate vasodilatation during labor to increase
      myometrial blood flow. Neither estradiol nor progesterone at the dosages studied
      changed prostacyclin synthase expression in the nonpregnant myometrium and
      endometrium. The molecular mechanism or mechanisms that differentially regulate
      prostacyclin synthase expression in pregnant uterine tissues merit further study.

PMID- 10076158
TI  - The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth
      restriction.
AB  - OBJECTIVE: Our purpose was to determine whether the Doppler cerebroplacental
      ratio predicts perinatal outcome in fetuses at risk for intrauterine growth
      restriction. STUDY DESIGN: The middle cerebral and umbilical artery pulsatility
      index values were measured in 203 fetuses at risk for intrauterine growth
      restriction, of which 123 were delivered <3 weeks after the last Doppler
      examination. Perinatal outcome was categorized as (1) birth weight <10th
      percentile, (2) birth weight <5th percentile, (3) perinatal complications
      (meconium-stained fluid, cesarean section for fetal distress, 5-minute Apgar
      score <7, perinatal death, neonatal intensive care unit stay >24 hours,
      hypoglycemia, or polycythemia), (4) birth weight <10th percentile plus
      complications, and (5) birth weight <5th percentile plus complications. The
      cerebroplacental ratio (middle cerebral artery pulsatility index divided by
      umbilical artery pul-satility index) values were expressed as multiples of the
      normal median. Receiver-operator characteristic curves (sensitivity vs false
      positive rates) were plotted for the prediction of each category of perinatal
      outcome and the areas under the curves were determined. Stepwise logistic
      regression analyses were used to determine whether the cerebroplacental ratio
      improved outcome prediction over umbilical artery Doppler imaging alone. RESULTS:
      There was a statistically significant increase in perinatal morbidity and
      mortality in cases with an abnormal cerebroplacental ratio. The areas under the
      receiver-operator curves characteristics for the prediction of perinatal outcome
      with use of the cerebroplacental ratio were statistically very significant. For
      birth weight <10th percentile we noted P <.001, with P <.0001 for each of the
      other 4 outcome categories. As shown by regression analyses, the cerebroplacental
      ratio appeared to improve the prediction of perinatal outcome compared with
      umbilical artery velocimetry alone. An interesting finding was that the
      cerebroplacental ratio did not appear to correlate significantly with outcome in
      fetuses at >34 weeks. CONCLUSION: Doppler identification of the fetal "brain
      sparing" effect strongly predicts outcome in fetuses at risk for intrauterine
      growth restriction. The brain-sparing effect predicted perinatal problems only in
      fetuses <34 weeks' gestation at the Doppler examination.

PMID- 10076159
TI  - Risk factors for neonatal death in twin gestations in the state of South
      Carolina.
AB  - OBJECTIVE: The aim of the study was to describe risk factors for neonatal death
      among twins born in South Carolina. STUDY DESIGN: South Carolina publicly
      accessible live birth and infant death cohort files for live-born twins >500 g
      were reviewed for the years 1988 through 1993. Infants with lethal anomalies were
      deleted from the cohort before analysis. Risk factors for neonatal death were
      determined for the entire cohort and for the birth weight categories of 500 to
      999 g, 1000 to 1499 g, 1500 to 2499 g, and >/=2500 g. Statistical comparisons
      were performed with the Mantel-Haenszel chi2 test and multivariate logistic
      regression. RESULTS: Of 7833 live-born twins, 263 (3.4%) died during the neonatal
      period. The mean birth weight was 2357 +/- 650 g (range 500-5358 g) at a mean
      gestational age of 35.7 +/- 3.5 weeks. Overall neonatal mortality rates were
      significantly increased (P <.001) for twins whose mothers were nonwhite (4.2 vs
      2.8%), were <20 years old (6.0 vs 3.2%), or received no prenatal care (14.7 vs
      3.1%). After we controlled for population characteristics with multivariate
      techniques, analysis revealed birth weight <2500 g and residence in the most
      populous urban areas to be associated with increased neonatal mortality rates.
      After stratification into birth weight categories, race was no longer a
      significant variable; in fact, nonwhite twins had a survival advantage at birth
      weights <1500 g, but this was not significant. Maternal age <20 years was
      associated with a higher neonatal mortality rate for infants with birth weights
      between 1500 and 2499 g. Absence of prenatal care significantly increased the
      neonatal mortality rate for twins >/=1500 g but not for those who were smaller.
      For infants weighing 500 to 999 g neonatal mortality rates were significantly
      lower at hospitals with >/=2000 deliveries/y than at hospitals with lower
      delivery volumes (P =.005). CONCLUSIONS: Although the overall neonatal mortality
      rate for twins continues to improve, increased rates are still seen among blacks,
      teenagers, and women who receive no prenatal care. Twins between 500 and 999 g
      have significantly reduced neonatal mortality rates when delivered at hospitals
      with a high obstetric volume.

PMID- 10076160
TI  - Selective estrogen receptor modulators: Women's panacea for the next millennium?
AB  - The purpose of this review is to assimilate relevant experimental and clinical
      information available on selective estrogen receptor modulators with respect to
      their potential use as agents to improve women's health in the postmenopausal
      years. In addition, the mechanisms of action of these drugs are outlined.
      Selective estrogen receptor modulators represent an exciting group of
      antiestrogens that possess agonist action on bone, lipids, and lipoproteins and
      antagonistic action in the endometrium and breast. Thus in theory these drugs may
      preserve bone density and reduce the risk of osteoporotic fracture and coronary
      heart disease at the same time that they lower the incidences of breast and
      endometrial neoplasms. Short-term data with the use of raloxifene suggest that
      bone is preserved and lipid profiles are less atherogenic. Long-term studies are
      needed to determine whether raloxifene or other selective estrogen receptor
      modulators are associated with any decrease in the risk of breast or endometrial
      cancer.

PMID- 10076161
TI  - Triplet pregnancy: A difficult challenge in perinatal medicine.

PMID- 10076162
TI  - Speculoscopy.

PMID- 10076163
TI  - Laparoscopy-associated intestinal infarction: A new syndrome?

PMID- 10076169
TI  - Androgen cotherapy in menopause: evolving benefits and challenges.
AB  - The hormonal effects of estrogen and androgen were first investigated at the
      beginning of the twentieth century. Estrogen, which was first synthesized in the
      1920s, has been shown to improve menopausal symptoms, decrease the incidence of
      osteoporosis, have a beneficial impact on plasma lipid profiles, probably reduce
      ischemic cardiovascular disease, and possibly improve cognition. In addition,
      retrospective studies have found a decreased incidence of Alzheimer's disease
      among women receiving estrogen replacement therapy compared with those not
      receiving this form of postmenopausal therapy. Androgen has been written about in
      the medical literature since 1936, when Mocquot and Moricard described its use to
      relieve vasomotor symptoms in postmenopausal women. During the 1940s and 1950s
      numerous reports appeared in the literature describing the effectiveness of
      estrogen-androgen combination therapy for improving the overall feeling of well
      being, energy level, libido, and quality of life for postmenopausal women. Recent
      studies have also shown estrogen-androgen therapy to contribute to the prevention
      of osteoporosis and reduce serum levels of total cholesterol, triglycerides, low
      density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Both
      historical data and evolving data support further evaluation of the use of
      estrogen-androgen replacement therapy in postmenopausal women.

PMID- 10076170
TI  - Vasomotor flushes in menopausal women.
AB  - Vasomotor symptoms after menopause are multifactorial in origin but result
      primarily from the loss of estrogen as ovarian function ceases. Although hot
      flushes typically last for 0.5 to 5.0 years after natural menopause, they may
      persist for as long as 15 years in a small percentage of postmenopausal women. In
      contrast, hot flushes tend to last longer and be more severe in surgically
      menopausal women. One of the major complaints associated with vasomotor symptoms
      is insomnia, which can have a domino effect on the patient's overall quality of
      life. Conventional hormone replacement therapy is effective in controlling
      vasomotor symptoms, including insomnia, for most postmenopausal women. However,
      data suggest that estrogen-androgen replacement therapy provides additional
      relief for women with persistent or severe vasomotor symptoms, especially women
      scheduled to undergo surgical menopause.

PMID- 10076171
TI  - Patient profile 1: unresolved vasomotor symptoms with conventional hormone
      replacement therapy.

PMID- 10076172
TI  - Psychosexual effects of menopause: role of androgens.
AB  - Ovarian hormones-estrogens, androgens, and progesterone-produce a myriad of
      effects in the nervous system. The effects of androgens in the brain are mediated
      through androgen-specific receptors and by the aromatization of testosterone to
      estradiol. Alterations in the circulating levels of androgens play an important
      role in psychologic and sexual changes that occur after menopause. The effects of
      short-term estrogen therapy in improving psychologic symptoms, maintaining
      vaginal lubrication, decreasing vaginal atrophy, and increasing pelvic blood flow
      in postmenopausal women are well documented. However, some patients require more
      than estrogen alone to improve psychologic dysfunction, decreased sexual desire,
      or other sexual problems associated with menopause. Results from clinical studies
      show that hormone replacement therapy with estrogen plus androgens provides
      greater improvement in psychologic (eg, lack of concentration, depression, and
      fatigue) and sexual (eg, decreased libido and inability to have an orgasm)
      symptoms than does estrogen alone in naturally and surgically menopausal women.

PMID- 10076173
TI  - Role of androgens in surgical menopause.
AB  - For the patient who has had her ovaries and uterus removed, the acute onset of
      surgical menopause is of primary concern during the immediate postoperative
      period. The initiation of hormone replacement therapy at this time eliminates
      most symptoms that result from the abrupt onset of menopause. Thus the patient
      can deal with the side effects from her operation without the added burden caused
      by the physiologic changes from the loss of her gonadal hormones. Most patients
      who undergo surgical menopause (total abdominal hysterectomy with bilateral
      salpingo-oophorectomy) at the McGill University Menopause Clinic receive estrogen
      androgen replacement therapy in the recovery room. This occurs provided that the
      diagnosis is not cancer of the uterus and there are no other serious
      contraindications to hormone replacement therapy. Vasomotor flushes are almost
      entirely eliminated with estrogen-androgen replacement therapy. In addition, the
      androgen component of this regimen provides an increased healing effect because
      of its anabolic property. After 6 months we discuss whether estrogen-androgen
      replacement therapy should be continued or the therapy should be changed to
      estrogen replacement therapy only. Sexual desire and arousal, well-being, and
      energy level are enhanced by the addition of androgen. Side effects such as mild
      hirsutism are dose related and can be managed easily by dose reduction. Treatment
      with estrogen-androgen replacement therapy may be continued indefinitely if
      guidelines are followed and the patient is satisfied.

PMID- 10076174
TI  - Patient profile 2: surgical menopause.

PMID- 10076175
TI  - Androgens and bone: clinical implications for menopausal women.
AB  - Osteoporosis is a common problem, affecting >28 million Americans, >/=75% of whom
      are postmenopausal women. In 1995 the cost of caring for patients with
      complications of osteoporosis was $14 billion. Of the 1.5 million osteoporotic
      fractures that occur in this country each year, the most serious are hip
      fractures. It is estimated that approximately 10% to 20% of women die within a
      year after a hip fracture. Numerous studies reveal that although osteoporotic
      fractures are preventable most women are not receiving or choosing to receive the
      medical care that they need to prevent them. Great strides have been made in
      establishing the importance of ovarian hormones in not only the pathophysiology
      but also the treatment of postmenopausal osteoporosis. Clinical studies show that
      estrogen and estrogen-androgen replacement therapies both prevent the development
      of osteoporosis, as determined by bone mineral density determinations and bone
      marker analyses. The addition of an androgen to hormone replacement therapy may
      prevent bone loss and stimulate bone formation.

PMID- 10076176
TI  - Patient profile 3: decreased libido and bone mineral density in a naturally
      menopausal woman.

PMID- 10076177
TI  - Improving adherence to hormone replacement therapy with effective patient
      physician communication.
AB  - Surgically menopausal women are 5 times more likely to begin hormone replacement
      therapy than are naturally menopausal women, and they continue therapy for longer
      periods. The primary reasons that women refuse hormone replacement are fear of
      cancer and perceived side effects. In contrast, withdrawal bleeding is the major
      reason that women discontinue hormone replacement therapy. Physician-patient
      communication plays an important role in a woman's decision to use hormone
      replacement therapy, to fill her prescription, and to adhere to the regimen. The
      first visit at which hormone replacement therapy is discussed is crucial to
      establishing an effective patient-physician relationship. At least 15 minutes,
      and preferably 45 minutes, should be reserved for this visit. Patient follow-up
      either by phone or in person-during the first month can help improve adherence
      because this is when many women may have nuisance side effects and discontinue
      therapy.

PMID- 10076178
TI  - Tissue-specific changes of type 1 angiotensin II receptor and angiotensin
      converting enzyme mRNA in angiotensinogen gene-knockout mice.
AB  - This study examined whether type 1 angiotensin II receptor (AT1) and angiotensin
      converting enzyme (ACE) mRNAs are regulated during dietary salt loading in
      angiotensinogen gene-knockout (Atg-/-) mice which are genetically deficient in
      endogenous production of angiotensin II. Wild-type (Atg+/+) and Atg-/- mice were
      fed a normal-salt (0.3% NaCl) or a high-salt (4% NaCl) diet for 2 weeks. The mRNA
      levels were measured by Northern blot analysis. In Atg+/+ mice, concentrations of
      plasma angiotensin peptides were decreased by salt loading, whereas the treatment
      increased the brainstem, cardiac, pulmonary, renal cortex, gastric and intestinal
      AT1 mRNA levels. Salt loading also enhanced renal cortex ACE mRNA levels in
      Atg+/+ mice. Although plasma angiotensin peptides and urinary aldosterone
      excretion were not detected in Atg-/- mice, salt loading increased blood pressure
      in Atg-/- mice. In Atg-/- mice, pulmonary, renal cortex, gastric and intestinal
      AT1, and renal cortex and intestinal ACE mRNA levels were higher than those in
      Atg+/+ mice. However, salt loading upregulated AT1 mRNA expression only in the
      liver of Atg-/- mice, and the treatment did not affect ACE mRNA levels in Atg-/-
      mice. Furthermore, although the levels of ACE enzymatic activity showed the same
      trend with the ACE mRNA levels in the lung, renal cortex and intestine of both
      Atg-/- and Atg+/+ mice, the results of radioligand binding assay showed that
      cardiac expression of AT1 protein was regulated differently from AT1 mRNA
      expression both in Atg-/- and Atg+/+ mice. Thus, expression of AT1 and ACE is
      regulated by salt loading in a tissue-specific manner that appears to be
      mediated, at least partly, by a mechanism other than changes in the circulating
      or tissue levels of angiotensin peptides.

PMID- 10076179
TI  - Growth factors and goitrogenesis.
AB  - By combining data from studies of multinodular non-toxic goitre (MNTG) with data
      from rat models of goitre induction and in vitro models, a map of the growth
      factors involved in goitrogenesis has been constructed. We have addressed the
      roles of the insulin-like growth factors, transforming growth factors, fibroblast
      growth factors, endothelins, etc. We hypothesise that an imbalance in the
      interactions between the various growth factor axes exists in MNTG which favours
      cell replication. Thyrotrophin, although not significantly elevated in MNTG,
      exerts critical effects through interactions with autocrine and paracrine factors
      and their receptors. Expansion of the thyroidal vascular bed through angiogenesis
      is closely co-ordinated with follicular cell expansion and folliculoneogenesis,
      and while the integrated paracrine actions of fibroblast growth factors, vascular
      endothelial growth factor and endothelin probably play central roles, additional,
      as yet elusive, factors are probably involved. The combination of in vitro and in
      vivo approaches, designed to address specific questions, will undoubtedly
      continue to prove invaluable in dissecting further the complex interactions that
      exist between these growth factors, their binding proteins and receptors in
      goitrogenesis.

PMID- 10076180
TI  - Developmental changes in LH secretion by male pituitaries in vitro: from the
      infantile to adult period.
AB  - The secretion of LH from the anterior pituitary of male rats was studied at
      different periods of postnatal development. According to an established
      classification we used rats 14 (infantile), 23 (juvenile), 45 (pubertal) and 90
      (adult) days old. By using an in vitro incubation system, both basal and
      stimulated LH secretion were studied in the same gland. Age-related differences
      were observed in basal LH secretion, with juvenile and pubertal pituitaries
      showing higher secretion compared with infantile and adult pituitaries. However,
      the GnRH-induced secretory response was significantly higher in the infantile
      rats than in other ages. LH secretion was also studied in primary cultures from
      infantile or adult pituitaries. In 24 and 48 h cultures, infantile cells showed a
      significantly larger response to GnRH than that of adult cells. In the infantile
      pituitary LH-immunopositive cells showed differences in size at different
      locations in the gland. At the periphery of the lobes the predominant cells were
      smaller and angular shaped, whereas in the center of the gland the majority of
      the cells were ovoid shaped. In the adult pituitary, the predominant LH-positive
      cells were ovoid in shape and larger in size. Furthermore, 10% more LH-positive
      cells were observed in infantile pituitaries. On the basis of these data we
      propose that at the infantile period the male rat pituitary has two populations
      of LH-secreting cells, one with adult secretory function and shape and a second
      with increased sensitivity to GnRH and with a morphology atypical of the adult
      cell. The results presented support the hypothesis that the infantile period is a
      transitional stage in the rat pituitary development.

PMID- 10076181
TI  - Local regulation of vasopressin and oxytocin secretion by extracellular ATP in
      the isolated posterior lobe of the rat hypophysis.
AB  - It is now widely accepted that ATP functions as a signalling substance in the
      nervous system. The presence of P2 receptors mediating the action of
      extracellular ATP in brain regions involved in hormonal regulation raises the
      possibility that a similar role for ATP might also exist in the neuroendocrine
      system. In this study, the release from the rat isolated neurohypophysis
      preparation of endogenous ATP, oxytocin and vasopressin (AVP) were measured
      simultaneously using luciferin-luciferase and RIA techniques. After 70 min
      preperfusion, electrical field stimulation caused a rapid increase in the amount
      of ATP in the effluent and the release of AVP and oxytocin also increased
      stimulation-dependently. Inhibition of voltage-dependent Na+ channels by
      tetrodotoxin (1 microM) reduced the stimulation-evoked release of AVP and
      oxytocin; however, the evoked release of ATP remained unaffected. The effect of
      endogenous ATP on the hormone secretion was tested by suramin (300 microM), the
      P2 receptor antagonist. Suramin significantly increased the release of AVP, and
      the release of oxytocin was also enhanced. ATP, when applied to the superfusing
      medium, decreased the release of AVP, but not that of oxytocin, and its effect
      was prevented by suramin. ATP (60 nmol), added to the tissues, was readily
      decomposed to ADP, AMP and adenosine measured by HPLC combined with ultraviolet
      light detection, and the kinetic parameters of the enzymes responsible for
      inactivation of ATP (ectoATPase and ecto5'-nucleotidase) were also determined
      (Km=264+/-2.7 and 334+/-165 microM and vmax=6.7+/-1.1 and 2.54+/-0.24 nmol/min
      per preparation (n=3) for ectoATPase and ecto5'-nucleotidase respectively). Taken
      together, our data demonstrate the stimulation-dependent release, P2 receptor
      mediated action and extracellular metabolism of endogenous ATP in the posterior
      lobe of the hypophysis and indicate its role, as a paracrine regulator, in the
      local control of hormone secretion.

PMID- 10076182
TI  - Mediation of humoral catecholamine secretion by the renin-angiotensin system in
      hypotensive rainbow trout (Oncorhynchus mykiss).
AB  - The individual contributions of, and potential interactions between, the renin
      angiotensin system (RAS) and the humoral adrenergic stress response to blood
      pressure regulation were examined in rainbow trout. Intravenous injection of the
      smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in
      dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and
      significant increases in plasma angiotensin II (Ang II) and catecholamine
      concentrations. Blockade of alpha-adrenoceptors before papaverine treatment
      prevented PDA and RS recovery, had no effect on the increase in plasma
      catecholamines, and resulted in greater plasma Ang II concentrations.
      Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4)
      mol/kg), before papaverine treatment attenuated the increases in the plasma
      concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%,
      respectively and also prevented PDA and RS recovery. By itself, lisinopril
      treatment caused a gradual and sustained decrease in PDA and RS, and reductions
      in basal plasma Ang II and adrenaline concentrations. Bolus injection of a
      catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in
      the lisinopril+papaverine-treated trout, to supplement their circulating
      catecholamine concentrations and mimic those observed in fish treated only with
      papaverine, resulted in a temporary recovery in PDA and RS. These results
      indicate that the RAS and the acute humoral adrenergic response are both
      recruited during an acute hypotensive stress, and have important roles in the
      compensatory response to hypotension in rainbow trout. However, whereas the
      contribution of the RAS to PDA recovery is largely indirect and relies on an Ang
      II-mediated secretion of catecholamines, the contribution from the adrenergic
      system is direct and relies at least in part on plasma catecholamines.

PMID- 10076183
TI  - Demonstration of in vivo mammogenic and lactogenic effects of recombinant ovine
      placental lactogen and mammogenic effect of recombinant ovine GH in ewes during
      artificial induction of lactation.
AB  - The present study demonstrates that ovine placental lactogen (oPL) (ovine
      chorionic somatotrophin) may have an important role in the mammogenesis and/or
      lactogenesis of the ewe. Its effects were compared with that already described
      for ovine growth hormone (oGH). In the first experiment, 40 nulliparous ewes were
      induced to lactate by means of a 7 day (days 1-7) oestro-progestative treatment
      (E2+P4). The ewes from Group 1 (n=12) received no further treatment, while those
      of the other groups received either recombinant oGH (roGH, 28 micrograms/kg,
      i.m., twice daily, Group 2, n=12) or recombinant oPL (roPL, 79 micrograms/kg,
      i.m., twice daily, Group 3, n=12) from day 11 to 20. All ewes received 25 mg
      hydrocortisone acetate (HC) twice daily on days 18-20. Control Group 00 (n=2)
      received no steroid treatment at all, and the control Group 0 (n=2) received only
      the E2+P4 treatment. Thirteen ewes (three from each experimental group and the
      two of each control group) were slaughtered at the end of hormone treatments (day
      21) before any milking stimulus. The 27 remaining ewes from Groups 1-3 were
      machine-milked and milk yields recorded daily from day 21 to 76. The E2+P4
      treatment enhanced the plasma levels of oPRL, oGH and IGF-I between days 1 and 7
      by 1.5, 2. 3 and 2.6 times respectively (P=0.002); roGH treatment induced a
      highly significant enhancement of IGF-I plasma levels from day 11 to 20, whereas
      a similar effect appeared for roPL-treated ewes only from day 17 to 20 (P<0.01).
      Eight weeks after the last exogenous hormone injections, milk yields of both roGH
      and roPL-treated groups progressively rose to twice that of unsupplemented
      groups (P<0.001). The mammary DNA content on day 21 was higher for animals which
      received either oGH or oPL but, due to individual variations in so few samples
      (n=3), this difference was not significant. No beta-casein was measured in
      mammary tissue from control ewes, whereas steroid-treated ewes (E2+P4+HC) had
      higher casein concentrations regardless of subsequent hormonal treatment on days
      11-20 (P<0.001). beta-Casein concentrations in mammary parenchyma of roGH-treated
      ewes did not differ from that of ewes which received only E2+P4+HC; roPL
      supplementation clearly enhanced expression of beta-casein (P<0.001). IGF-I
      stimulation by either roGH or roPL was more precisely examined during a second
      experiment, in which two twice-daily i.m. doses (58 or 116 micrograms/kg) of
      either roGH or roPL were administered to four groups of six ewes that were E2+P4
      treated as those of Experiment 1. A control group (n=6) received no exogenous
      hormone from day 11 to 13. On day 13, hourly blood samples were taken from all
      ewes over 11 h. Both doses of roGH significantly stimulated IGF-I in a dose
      dependent manner. The 58 micrograms/kg dose of roPL did not significantly
      stimulate IGF-I, but although being somewhat less efficient than the 58
      micrograms/kg dose of roGH, the 116 micrograms/kg dose of roPL significantly
      stimulated IGF-I secretion (P<0. 001). These results suggest that mammogenesis
      and/or lactogenesis in the ewe is in part controlled by somatotrophic hormones
      such as oGH and oPL and that IGF-I could be one of the mediators of these
      hormones.

PMID- 10076184
TI  - Characterisation of recombinant glycosylation variants of insulin-like growth
      factor binding protein-3.
AB  - There are three potential N-glycosylation sites in the non-conserved central
      region of the insulin-like growth factor binding protein-3 (IGFBP-3) sequence
      (N89AS, N109AS, N172FS). IGFBP-3 exists as two glycoforms which reduce to a
      single form on enzymatic deglycosylation. To determine the functional
      significance of the carbohydrate chains, the N-glycosylation sites were mutated
      singly and in combinations by substituting Asn residues with Ala. Each
      recombinant glycoform was detected by radioimmunoassay, indicating that
      glycosylation is not essential for secretion in Chinese hamster ovary cells.
      Ligand blotting of the conditioned media using [125I]IGF-I indicated that all
      seven mutants are active. On the basis of the number and molecular masses of the
      bands detected for each glycoform, there is approximately 4, 4.5 and 5 kDa of
      carbohydrate on Asn89, Asn109 and Asn172 respectively, with variable occupancy of
      Asn172. Ternary complex formation by the glycovariants in the presence of ALS and
      excess IGF-I was not significantly different from that of fully glycosylated
      recombinant human (rh)IGFBP-3 [Ka (fully glycosylated)=12.5+/-4.1 l/nmol; mean Ka
      (all mutants)=22.1+/-3.0 l/nmol]. In contrast, Asn to Asp substitutions decreased
      acid-labile subunit (ALS) binding activity. Cell-surface association experiments
      indicate that glycosylation may influence the partitioning of IGFBP-3 between the
      extracellular milieu and the cell surface. Therefore, while the carbohydrate
      units appear to be non-essential to ALS or IGF binding, they may modulate other
      biological activities of IGFBP-3.

PMID- 10076185
TI  - Nicotinamide decreases MHC class II but not MHC class I expression and increases
      intercellular adhesion molecule-1 structures in non-obese diabetic mouse
      pancreas.
AB  - Pancreases of untreated and nicotinamide (NIC)-treated pre-diabetic (10-week-old)
      and overtly diabetic (25-week-old) female NOD (non-obese diabetic) mice and of
      NON (non-obese non-diabetic) control mice were studied, with the following
      results. (1) Islets and ducts of overtly diabetic untreated NOD mice (25-week
      old) were found to express low levels of MHC class I and II molecules, like NON
      controls, and high levels of adhesive molecules. (2) NIC was able to slightly
      affect glycaemia and insulitis, slowing down diabetes progression. Moreover it
      significantly decreased MHC class II expression (but not class I) in vivo by week
      10, and significantly enhanced intercellular adhesion molecule-1 (ICAM-1)
      expression, mainly by week 25, within the pancreas, where 5-bromo-2'-deoxyuridine
      positive nuclei and insulin positive cells were present, demonstrating that a
      stimulation of endocrine cell proliferation occurs. (3) In addition, NIC partly
      counteracted the fall of superoxide dismutase levels, observed in untreated
      diabetic NOD animals. (4) In vitro studies demonstrated that NIC: (i) was able to
      significantly reduce nitrite accumulation and to increase NAD+NADH content
      significantly, and (ii) was able to increase the levels of interleukin-4, a T
      helper 2 lymphocyte (Th2) protective cytokine, and of interferon-alpha (IFN
      alpha), which is known to be able to induce MHC class I and ICAM-1 but not MHC
      class II expression, as well as IFN-gamma, which is also known to be able to
      induce MHC class I and ICAM-1 expression. The latter, although known to be a
      proinflammatory Th1 cytokine, has also recently been found to exert an anti
      diabetogenic role. This study therefore clearly shows that adhesive mechanisms
      are ongoing during the later periods of diabetes in pancreatic ducts of NOD mice,
      and suggests they may be involved in a persistence of the immune mechanisms of
      recognition, adhesion and cytolysis and/or endocrine regeneration or
      differentiation processes, as both NIC-increased ICAM-1 expression and 5-bromo-2'
      deoxyuridine positivity imply. The effects of NIC on MHC class II (i.e. a
      reduction) but not class I, and, mainly, on ICAM-1 expression (i.e. an increase),
      together with the increase in Th2 protective cytokine levels are very
      interesting, and could help to explain its mechanism of action and the reasons
      for alternate success or failure in protecting against type 1 diabetes
      development.

PMID- 10076186
TI  - Insulin-secreting activity of the traditional antidiabetic plant Viscum album
      (mistletoe).
AB  - Viscum album (mistletoe) has been documented as a traditional treatment of
      diabetes. In acute 20-min tests, 1-10 mg/ml aqueous extract of mistletoe evoked a
      stepwise 1.1- to 12.2-fold stimulation of insulin secretion from clonal
      pancreatic B-cells. This effect was abolished by 0.5 mM diazoxide and prior
      exposure to extract did not alter subsequent stimulation of insulin secretion
      induced by 10 mM L-alanine, thereby negating a detrimental effect on cell
      viability. The insulin-releasing effect of mistletoe extract was unaltered by
      16.7 mM glucose, l-alanine (10 mM), 3-isobutyl-1-methylxanthine (IBMX) (1 mM), or
      a depolarising concentration of KCl (25 mM). The ability of extract to enhance
      insulin secretion did not depend upon the use of heat during extract preparation
      and was not mediated by lectins. These results demonstrate the presence of
      insulin-releasing natural product(s) in Viscum album which may contribute to the
      reported antidiabetic property of the plant.

PMID- 10076187
TI  - Transforming growth factor-beta1 is a potent inhibitor of interleukin-1beta
      action in whole ovarian dispersates.
AB  - Transforming growth factor beta1 (TGFbeta1) acts as an inhibitor of the actions
      of interleukin-1beta (IL-1beta) in various organ systems. In order better to
      understand the inter|P-actions between these polypeptides in the ovary, we
      evaluated the effect of TGFbeta1 co-treatment on various IL-1beta-mediated
      actions in cultures of whole ovarian dispersates. Treatment with IL-1beta
      enhanced media accumulation of nitrites (4.8-fold), prostaglandin E2 (PGE2, 3. 9
      fold) and lactate (2.0-fold), and enhanced glucose consumption (2. 1-fold).
      Treatment with TGFbeta1 alone did not significantly affect any of these
      parameters. However, the addition of TGFbeta1 inhibited IL-1beta-stimulated
      nitrite (100%), PGE2 (44%) and lactate (78%) accumulation and inhibited IL-1beta
      stimulated glucose consumption (74%) in a dose-dependent manner. The addition of
      TGFbeta1 also suppressed the steady-state levels of IL-1beta-stimulated IL-1beta,
      type I IL-1 receptor and IL-1 receptor antagonist transcripts (98, 67 and 83%
      inhibition respectively). These data suggest that TGFbeta1 is capable of
      inhibiting several IL-1beta-stimulated endpoints. Since IL-1 has been identified
      as a possible proinflammatory mediator of ovulation and TGFbeta has been
      implicated as a promotor of fibrosis and healing, we speculate that IL-1 and
      TGFbeta might play antagonistic roles in the normal ovulatory sequence.

PMID- 10076188
TI  - Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone
      sulphate inhibit leptin secretion in female but not in male samples of omental
      adipose tissue in vitro: lack of effect of testosterone.
AB  - Leptin, the product of the Ob gene, is a polypeptide hormone expressed in
      adipocytes which acts as a signalling factor from the adipose tissue to the
      central nervous system, regulating food intake and energy expenditure. It has
      been reported that circulating leptin levels are higher in women than in men,
      even after correction for body fat. This gender-based difference may be
      conditioned by differences in the levels of androgenic hormones. To explore this
      possibility, a systematic in vitro study with organ cultures from human omental
      adipose tissue, either stimulated or not with androgens (1 microM), was
      undertaken in samples obtained from surgery on 44 non-obese donors (21 women and
      23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no
      apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the
      integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h.
      Spontaneous leptin secretion in samples from female donors (4149+/-301) was
      significantly higher (P<0.01) than that from male donors (2456+/-428).
      Testosterone did not exert any significant effect on in vitro leptin secretion in
      either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose
      tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin
      decrease in samples taken from women (3119+/-322) but not in those taken from men
      (2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin
      secretion in female samples (2809+/-383) but not in male (1553+/-671).
      Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin
      decrease in female samples (2996+/-473), with no modifications in samples derived
      from males (1596+/-528). Exposure to androstenedione also resulted in a
      significant reduction (P<0.01) of leptin secretion in samples taken from women
      (2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion,
      DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of
      in vitro leptin secretion in samples from female donors, without affecting the
      secretion in samples from men. Testosterone was devoid of activity in either
      gender.

PMID- 10076189
TI  - Pancreatic acinar AR42J cells express functional nerve growth factor receptors.
AB  - The factors regulating the differentiation of the endocrine cells of the pancreas
      are still unknown. In previous studies, we have demonstrated that, like neurones,
      various beta-cell lines express functional neurotrophin receptors. Moreover, Trk
      A, the nerve growth factor (NGF) high-affinity receptor, is expressed in vivo in
      mature rat islets and early during development in the pancreatic ductal network
      that represents the source of putative stem cells. Rat pancreatic AR42J cells
      possess both exocrine and neuroendocrine properties. Recent studies have shown
      that these cells can differentiate either into acinar cells or into insulin
      expressing cells. In this study, we demonstrate that AR42J cells, in common with
      the embryonic ductal cells, do express Trk-A. Moreover, on treatment with NGF,
      Trk-A is phosphorylated and early responsive genes such as NGFI-A, c-fos and c
      jun are induced. These results clearly show that the Trk-A receptor expressed in
      AR42J is functional. AR42J cells provide a model system with which to study the
      role of NGF in the development of the pancreatic cells.

PMID- 10076190
TI  - High concentration of glucose decreases glucose transporter-1 expression in mouse
      placenta in vitro and in vivo.
AB  - Facilitative glucose transporter-1 (GLUT1) is expressed abundantly and has an
      important role in glucose transfer in placentas. However, little is known about
      the regulation of GLUT1 expression in placental cells. We studied the changes in
      placental GLUT1 levels in relation to changes in glucose concentration in vitro
      and in vivo. In in vitro experiments, dispersed mouse placental cells were
      incubated under control (5.5 mM) and moderately high (22 mM) glucose
      concentrations, and 2-deoxyglucose uptake into cells was studied on days 1-5 of
      culture. After 4 days of incubation under both conditions, GLUT1 mRNA and proten
      levels were examined by Northern and immunoblot analyses. Treatment of cells with
      22 mM glucose resulted in a significant decrease in 2-deoxyglucose uptake
      compared with control, from day 2 to day 5 of culture. Moreover, GLUT1 mRNA and
      protein levels on day 4 of culture were significantly reduced in cells incubated
      with 22 mM glucose compared with control. Next, we rendered mice diabetic by
      administering 200 micrograms/g body weight streptozotocin (STZ) on day 8 of
      pregnancy. Animals were killed on day 12 of pregnancy and placental tissues were
      obtained. [3H]Cytochalasin B binding study was carried out to assess total GLUTs,
      and GLUT1 mRNA and protein were measured as above. [3H]Cytochalasin B binding
      sites in placentas from STZ-treated mice were significantly less than those in
      control mice. Northern and immunoblot analyses revealed a significant decrease in
      GLUT1 mRNA and protein levels in diabetic mice compared with the controls. These
      findings suggest that the glucose concentration may regulate the expression of
      placental GLUT1.

PMID- 10076191
TI  - Stimulation of Na,K-ATPase by hypothyroidism in the thyroid gland.
AB  - Although studies have documented the regulatory effects of thyroid hormones on
      the Na,K-ATPase in peripheral tissues, there is little information on the
      regulation of this transporter in the thyroid gland itself. Accordingly, we
      investigated the effects of thyroid status on Na,K-ATPase specific activity and
      the abundance of its constituent subunits in rat thyroid. Exogenous tri
      iodothyronine (T3) was administered daily to produce hyperthyroidism. 6n-propyl-2
      thiouracil (PTU), an inhibitor of thyroid hormone synthesis, was used to induce
      hypothyroidism. There was a four-fold increase in Na,K-ATPase specific activity
      in the follicular membranes from PTU-treated animals after 7 days. Enzymatic
      activities were not changed in the T3-treated glands. Immunoblotting of membranes
      from T3-treated rats revealed a 75% reduction in alpha1 subunit abundance and a
      slight, but nonsignificant reduction in beta1 abundance. On the other hand, the
      membranes from PTU-treated rats displayed 136 and 567% increases in the abundance
      of the alpha1 and beta1 subunits respectively. These data demonstrate that
      thyroid hormone status regulates Na,K-ATPase in the gland, but the effects are in
      direct contrast to those seen in the periphery.

PMID- 10076192
TI  - Spatiotemporal expression of alternatively spliced IGF-I mRNA in the rat
      costochondral growth plate.
AB  - IGF-I acts as a local proliferation and maturation factor for chondrocytes in the
      growth plate. However, the expression of different alternative IGF-I mRNA classes
      in the growth plate has not been characterized. Using quantitative reverse
      transcription PCR, the abundance of each alternative IGF-I mRNA class in resting,
      proliferative and hypertrophic chondrocytes was measured in rat costochondral
      growth plates. Class 1Ea mRNA was the most abundant IGF-I transcript overall and
      was highly expressed in proliferative chondrocytes at 2 and 4 weeks of age; by 6
      weeks, the majority of 1Ea mRNA expression had shifted to hypertrophic
      chondrocytes. Class 1Eb mRNA was the second most abundant transcript and its
      distribution was uniform across all the cell types at 2 weeks of age. The
      expression pattern changed with increasing age such that at 6 weeks a gradient
      existed with hypertrophic chondrocytes expressing higher levels of 1Eb than
      resting chondrocytes. Class 2Ea mRNA was constitutively expressed at low levels
      across the growth plate at all ages, while class 2Eb mRNA expression was
      negligible. The distribution of total IGF-I mRNA also shifted across growth plate
      cell types as the animals aged from 2 to 6 weeks. These findings suggest that IGF
      I class 1 mRNA plays the predominant role in the maturation of the growth plate.

PMID- 10076193
TI  - Suppression of the secretion of luteinizing hormone due to isolation/restraint
      stress in gonadectomised rams and ewes is influenced by sex steroids.
AB  - In this study we used an isolation/restraint stress to test the hypothesis that
      stress will affect the secretion of LH differently in gonadectomised rams and
      ewes treated with different combinations of sex steroids. Romney Marsh sheep were
      gonadectomised two weeks prior to these experiments. In the first experiment male
      and female sheep were treated with vehicle or different sex steroids for 7 days
      prior to the application of the isolation/restraint stress. Male sheep received
      either i.m. oil (control rams) or 6 mg testosterone propionate injections every
      12 h. Female sheep were given empty s.c. implants (control ewes), or 2x1 cm s.c.
      implants containing oestradiol, or an intravaginal controlled internal drug
      release device containing 0.3 g progesterone, or the combination of oestradiol
      and progesterone. There were four animals in each group. On the day of
      application of the isolation/restraint stress, blood samples were collected every
      10 min for 16 h for the subsequent measurement of plasma LH and cortisol
      concentrations. After 8 h the stress was applied for 4 h. Two weeks later, blood
      samples were collected for a further 16 h from the control rams and ewes, but on
      this day no stress was imposed. In the second experiment, separate control
      gonadectomised rams and ewes (n=4/group) were studied for 7 h on 3 consecutive
      days, when separate treatments were applied. On day 1, the animals received no
      treatment; on day 2, isolation/restraint stress was applied after 3 h; and on day
      3, an i. v. injection of 2 microg/kg ACTH1-24 was given after 3 h. On each day,
      blood samples were collected every 10 min and the LH response to the i.v.
      injection of 500 ng GnRH administered after 5 h of sampling was measured. In
      Experiment 1, the secretion of LH was suppressed during isolation/restraint in
      all groups but the parameters of LH secretion (LH pulse frequency and amplitude)
      that were affected varied between groups. In control rams, LH pulse amplitude,
      and not frequency, was decreased during isolation/restraint whereas in rams
      treated with testosterone propionate the stressor reduced pulse frequency and not
      amplitude. In control ewes, isolation/restraint decreased LH pulse frequency but
      not amplitude. Isolation/restraint reduced both LH pulse frequency and amplitude
      in ewes treated with oestradiol, LH pulse frequency in ewes treated with
      progesterone and only LH pulse amplitude in ewes treated with both oestradiol and
      progesterone. There was no change in LH secretion during the day of no stress.
      Plasma concentrations of cortisol were higher during isolation/restraint than on
      the day of no stress. On the day of isolation/restraint maximal concentrations of
      cortisol were observed during the application of the stressor but there were no
      differences between groups in the magnitude of this response. In Experiment 2,
      isolation/restraint reduced the LH response to GnRH in rams but not ewes and ACTH
      reduced the LH response to GnRH both in rams and ewes. Our results show that the
      mechanism(s) by which isolation/restraint stress suppresses LH secretion in sheep
      is influenced by sex steroids. The predominance of particular sex steroids in the
      circulation may affect the extent to which stress inhibits the secretion of GnRH
      from the hypothalamus and/or the responsiveness of the pituitary gland to the
      actions of GnRH. There are also differences between the sexes in the effects of
      stress on LH secretion that are independent of the sex steroids.

PMID- 10076194
TI  - Pituitary adenylate cyclase-activating polypeptide, interleukin-6 and
      glucocorticoids regulate the release of vascular endothelial growth factor in
      pituitary folliculostellate cells.
AB  - There is increasing evidence that hormones play an important role in the control
      of endothelial cell function and growth by regulating the production of vascular
      endothelial growth factor (VEGF). VEGF regulates vascular permeability and
      represents the most powerful growth factor for endothelial cells. In the normal
      anterior pituitary, VEGF has been detected only in folliculostellate (FS) cells.
      In the present study, the regulation of the release of VEGF from FS-like mouse
      TtT/GF cells, and from FS cells of rat pituitary monolayer cell cultures was
      investigated using a specific VEGF ELISA. Basal release of VEGF was demonstrated
      in cultures of both TtT/GF cells and rat pituitary cells. Interestingly, the VEGF
      secretion was stimulated by both forms of pituitary adenylate cyclase-activating
      polypeptide (PACAP-38 and PACAP-27), indicating that this hypothalamic peptide
      regulates endothelial cell function and growth within the pituitary. VEGF
      secretion was also stimulated by interleukin-6 (IL-6) whereas basal, IL-6- and
      PACAP-stimulated secretion was inhibited by the synthetic glucocorticoid
      dexamethasone. The inhibitory action of dexamethasone was reversed by the
      glucocorticoid receptor antagonist RU486, suggesting that in FS cells functional
      glucocorticoid receptors mediate the inhibitory action of glucocorticoids on the
      VEGF secretion. The endocrine and auto-/paracrine control of VEGF production in
      pituitary FS cells by PACAP, IL-6 and glucocorticoids may play an important role
      both in angiogenesis and vascular permeability regulation within the pituitary
      under physiological and pathophysiological conditions.

PMID- 10076195
TI  - Cloning and expression of a novel chicken sulfotransferase cDNA regulated by GH.
AB  - We have used mRNA differential display to compare gene expression in normal and
      GH receptor-deficient dwarf chickens, and report here the characterization of one
      differentially expressed gene, which shows significant sequence identity to the
      sulfotransferase gene family. Partial cDNA clones were isolated from a chicken
      liver cDNA library and an additional sequence was obtained using 5' rapid
      amplification of cDNA ends. A complete cDNA probe hybridizes to three transcripts
      (2.4, 2.0 and 1.45 kb) on Northern blots of chicken liver RNA, which differ in
      the length of the 3' untranslated region. All three transcripts are expressed at
      higher levels in normal vs dwarf chickens, as expected for a GH-regulated gene.
      The expression of this sulfotransferase mRNA was also detected in skeletal
      muscle, but not other tissues. The administration of GH to chickens increased the
      hepatic expression within 1 h, suggesting this sulfotransferase could be directly
      regulated by GH. Sulfotransferase activity, using estradiol or corticosterone as
      substrate, is detected in cells transfected with an expression vector containing
      the full-length cDNA. The sequence of this sulfotransferase does not show
      significant similarity with any subfamily of the sulfotransferases and its
      endogenous substrate is presently unknown. However, we speculate that GH
      activation of sulfotransferase activity could play a role in reducing
      concentrations of growth-antagonistic steroid hormones in GH target tissues.
      These results demonstrate the usefulness of differential display in this model
      system to identify genes that play a role in mediating GH action.

PMID- 10076196
TI  - Red laser pointers and color blindness.

PMID- 10076199
TI  - Vertical transmission of human papillomaviruses.

PMID- 10076200
TI  - The difference in group B Streptococcus prophylaxis protocols.

PMID- 10076201
TI  - Few observations are really new.

PMID- 10076202
TI  - Nurses must be protected by law from assault.

PMID- 10076203
TI  - Psychiatric nurses make a difference to patients.

PMID- 10076204
TI  - I.v.-related phlebitis, complications and length of hospital stay: 1.
AB  - This article, the first of two-parts, addresses the growing problem of
      intravenous-related phlebitis in hospitalized patients, and the resultant
      personal and financial costs to both patient and hospital. Literature on the
      various types of phlebitis, the factors that increase the patient's risk of
      developing phlebitis, clinical indicators and severity grading scales, and the
      complications of phlebitis are examined. Awareness of such factors is considered
      instrumental in minimizing the incidence of intravenous-related phlebitis. The
      second article in this series will present a study of 90 patients from a large
      teaching hospital, which was conducted to determine the incidence and severity of
      intravenous-related phlebitis, risk factors, associated complications, and the
      related length of hospital stay. The implications of the results for current and
      future nursing care of patients receiving i.v. therapy will be discussed, and
      recommendations for safe practice will be made.

PMID- 10076205
TI  - Adherence and compliance in the management of asthma: 1.
AB  - This article explores the issues surrounding compliance with treatment in
      patients with asthma. Epidemiological data (Pendleton, 1991) suggest that
      although overall mortality rates from asthma are falling, this is not the case in
      the adolescent and young adult age groups. Also, there has been little impact on
      morbidity figures for the disease. All of this is set against an expenditure of
      430 Pounds billion per annum on asthma medication. It would appear that patients
      are not complying with the prescribed treatment. This article examines the
      reasons for possible non-adherence with therapy and suggests that healthcare
      professionals must review their attitudes to this problem. The next article will
      examine in more detail issues relating to patients' adherence.

PMID- 10076206
TI  - Personal, professional and practice development: clinical supervision.
AB  - This article investigates current research concerns in relation to clinical
      supervision and offers a rationale for using case studies as a means of
      evaluation. Three case studies are used to illustrate how development and growth
      can occur as a result of clinical supervision. The use of case studies as a means
      of evaluation is analysed. Case studies provide unique insights into the dynamics
      and processes of clinical supervision. Any improvement in practice ought to bring
      about improvements in client care, thus case studies can add to the accumulating,
      qualitative data that support the link between clinical supervision and improved
      client care. This article recommends that more case studies should be carried out
      and that the findings are compiled on a centralized database in order that
      evidence supporting the widespread use of clinical supervision is readily
      accessible.

PMID- 10076207
TI  - The nurse's holding power: patterns of use in mental health.
AB  - Implementation of the nurse's holding power (Section 5(4) of the Mental Health
      Act 1983) is an important, yet poorly researched aspect of mental health nursing
      practice. Data collected from the Mental Health Act records of all patients
      detained under Section 5(4) in one trust from 1983 to 1997 suggest that detainees
      generally came from the acute mental health services, were female, were detained
      by male registered mental nurses and were held for an average of 2 hours and 24
      minutes before being placed on another section of the Mental Health Act. The use
      of Section 5(4) seems to be influenced by the time of day, but not the day of the
      week, or month of the year. Peaks of Section 5(4) usage corresponded to such
      factors as the changeover of shifts, the absence of medical staff, visiting time
      and medicine rounds. The importance of these findings for clinical practice is
      discussed.

PMID- 10076208
TI  - Interventions for confusion and dementia. 5: Changing cultures.
AB  - Previous articles in this series (Vol 7(15): 891-94; Vol 7(17): 1018-20; Vol
      7(19): 1145-49; Vol 7(20): 1247-50) have explored the promotion of quality of
      life for people with dementia and how this can be achieved through existing
      interventions. This final article moves from discussing specific interventions to
      cover wider issues around healthcare beliefs and values. A brief historical
      overview of dementia care is given, outlining the inherited structures and
      values. Much valuable work has been carried out by the Bradford Dementia Group,
      who has described changes in dementia care as moving from an 'old' to a 'new'
      culture. This 'new culture', offering a comprehensive person-centred approach to
      holistic care, is explored with reference to the work of Kitwood, who has done
      much to promote quality of life for people suffering from dementia.

PMID- 10076209
TI  - The Aquacath hydrophilic coated single-use urinary catheter.
AB  - Single-use hydrophilic catheters are now being used widely throughout this
      country, Europe and America, for intermittent self-catheterization or carer
      assisted intermittent catheterization, with considerable success. They are also
      reported to provide greater comfort for users. The latest catheter to become
      available on prescription is the Aquacath coated urinary catheter, produced by
      Seton Continence Care. This hydrophilic catheter performed very well in a trial
      comparing coating stability after wetting of various coated catheters (Jones,
      1997). The teaching of intermittent self-catheterization must conform to local
      protocols and trust agreements. Nurses should find out about these and follow
      them. When teaching any procedure or technique to untrained carers, the nurse
      must always remember that he/she has overall responsibility for supervision and
      ensuring safe practice.

PMID- 10076210
TI  - Hydrocoll: a 'new breed' of hydrocolloid wound dressing.
AB  - Hydrocolloid dressings were first used in wound management in the 1960s. They
      provide the optimal environment for wound healing, i.e. a moist environment,
      constant wound temperature and infrequent dressing changes, and can be used on
      wounds in various stages of healing. As a result they are a popular treatment
      option for health professionals in both the community and hospital settings. This
      article describes the properties of Hydrocoll--a new and exciting range of
      hydrocolloid dressings from Paul Hartmann Ltd--which was launched in the UK in
      January 1998 and became available on the Drug Tariff in June 1998.

PMID- 10076211
TI  - Medical interventions during pregnancy and childbirth.
AB  - The right of the medical profession to intervene during childbirth, contrary to
      the wishes of the patient, has been the subject of considerable legal debate
      during the 1990s. However, recent judicial comment in R vs Louize Collins and
      others [1998] seems to have reached a clear conclusion on the rights of the
      pregnant woman, and also the steps that can be taken to treat when a pregnant
      woman has refused intervention.

PMID- 10076212
TI  - Nursing says 'yes' to higher level practice.

PMID- 10076213
TI  - A higher level of practice is the way forward.

PMID- 10076214
TI  - Prison nursing: working at the cutting edge.

PMID- 10076215
TI  - I.v.-related phlebitis, complications and length of hospital stay: 2.
AB  - Review of the literature on the various types of phlebitis, risk factors,
      clinical indicators, severity grading scales, and associated complications of
      phlebitis, in the first article in this series (Vol 7(21): 1304-12), indicated
      that an awareness of such factors could reduce the incidence of intravenous
      (i.v.)-related phlebitis. This article presents a quantitative study, of
      longitudinal design, conducted to determine the incidence and severity of i.v.
      related phlebitis in 90 patients from a large teaching hospital over a 2-month
      period. The study concluded that although there were multiple risk factors for
      the development of phlebitis, routine IV site observation and the use of
      phlebitis severity measurement scales could reduce the incidence and severity of
      phlebitis. Complications arising from phlebitis can have long-term effects on
      patient care, satisfaction, and length of hospital stay. If not controlled, these
      risk factors can increase the personal and financial costs to patients, encourage
      litigation, and ultimately increase the overall costs to the hospital.

PMID- 10076216
TI  - Adherence and compliance in the management of asthma: 2.
AB  - The first article (Vol 7(21): 1313-15) in this two-part article examining the
      role of compliance in asthma management, discussed the concept of adherence to
      treatment. In this article, the role of the healthcare professional in improving
      adherence is discussed in greater depth. When attempting to improve patients'
      adherence to treatment, the healthcare professional must adopt a number of roles,
      e.g. counsellor, educator, negotiator and problem-solver. Practical advice and
      information is provided to facilitate an improved therapeutic alliance between
      professional and patient, with the emphasis on achieving shared goals.

PMID- 10076217
TI  - An update on the UKCC's work into higher level practice.
AB  - In the last specialist nursing supplement Sarah Waller described the background
      to the consultation process for recognizing and regulating a higher level of
      practice (Vol 7(16): 960-4). This article gives an overview of the responses to
      the consultation exercise and outlines what a higher level of practice will mean
      for the nursing profession. It was generally agreed that the present system of
      specialist practice is too complex and therefore confusing. In addition, the UKCC
      has recognized that professional practice has moved on since PREP and that there
      is a need to move away from a task-oriented and functionalist paradigm. It was
      also felt that the specialist framework is too narrow and does not cater for
      expert nurses who wish to stay in general, as opposed to specialist, clinical
      areas.

PMID- 10076218
TI  - Professional issues facing nurse practitioners and nursing.
AB  - Legislative changes relating to professional nursing practice and a reduction in
      junior doctors' working hours have led to an increase in the number of nurse
      practitioners in the UK. While the educational preparation for these new roles is
      varied, the challenges faced by nurse practitioners are similar in nature and
      have implications for the nursing profession as a whole. The measures that can
      facilitate the development of individual nurse practitioners include: effective
      communication and negotiation regarding the introduction of their role; clearly
      defined and documented role descriptions; clarification regarding areas of risk
      and liability; and organizational and professional support. The stance of the
      nursing profession in relation to the development of the nurse practitioner role
      is also explored and questions are raised about cross-boundary working, future
      role development, and the impact of nurse practitioners on the delivery of
      patient care.

PMID- 10076219
TI  - BRCA1 gene testing for breast and ovarian cancer in one family.
AB  - Most breast cancer is multifactorial in origin, but dominantly inherited genes
      are implicated in the development of approximately 5-10% of breast cancer as a
      whole. The identification of the BRCA1 gene, thought to account for 2% of all
      breast cancer and be present in almost all families affected by breast and
      ovarian cancer, makes testing for susceptibility to breast and ovarian cancer
      possible for the few families in which researchers have identified a gene
      mutation. Genetic counselling, by medically qualified geneticists, is available
      for people with rare genetic conditions caused by gene mutations. In this
      article, the authors describe their first experience of BRCA1 gene testing in 23
      family members. They identify a unique role within a new specialty, cancer
      genetics, for specialist nurse practitioners in genetic testing and counselling.

PMID- 10076220
TI  - Implementing evidence-based practice for urinary catheterization.
AB  - Nursing development units (NDUs) are ideal centres for the critical examination
      of clinical nursing practice. In addition, staff are enabled to clarify
      appropriate and effective methods of care and interventions based on evidence to
      date (Department of Health (DoH), 1993, 1998; English National Board (ENB), 1996,
      1997; Centre for Policy in Nursing Research, 1997). In July 1996, the staff
      within the cardiology NDU at Addenbrooke's NHS Trust looked at the potential for
      various projects that were central to practice. One concerned the management of
      urinary catheters. A pilot study was initiated, one outcome of which was the
      design of a project checklist based on Sackett et al's definition of evidence
      based practice (EBP) (Sackett et al, 1997). In this article, the aims and
      intentions of the project are evaluated in relation to the problems associated
      with implementing evidence. In addition, the framework of the White Paper (DoH,
      1998) is examined against the need for an organizational Infrastructure, which is
      required to enable achievement of the outcomes of EBP. The benefits of the
      project are outlined, both in the changes to practice and for the unit.
      Recommendations for other professionals are also offered, as there are few
      recorded experiences in the literature of implementation of EBP, the process
      framework required and the costs involved.

PMID- 10076221
TI  - RoHo Dry Floatation system: an alternative means of pressure relief.
AB  - Pressure sores are believed to occur as a result of two pressures, external
      pressure leading to occlusion, and disruptive shearing forces causing endothelial
      damage to the micro circulation. One of the main principles, therefore, of
      pressure sore prevention is relief or reduction of pressure. Scandinavian
      Mobility produces a range of systems--therapeutic cushions, specialist cushions
      and products, and mattresses--that can reduce the pressure, reportedly achieving
      interface pressures of 21-28 mmHg. These systems have been shown to be cost
      effective in the clinical setting and provide pressure relief in low-, medium-
      and high risk patients.

PMID- 10076222
TI  - Patient-focused care: primary responsibilities of research nurses.
AB  - This article provides a critical analysis of the concept of patient-focused care,
      and discusses its significance to the provision of nursing care in the UK today.
      Empowerment, as a component of patient-focused care, is addressed within the
      article in relation to government-led initiatives designed to afford certain
      rights to health consumers. It focuses specifically on the roles,
      responsibilities and concerns of the clinical research nurse in relation to
      patient-focused care and concludes that true patient-focused care will not happen
      until physicians, nurses and patients are educated and their attitudes changed.

PMID- 10076223
TI  - Should nurses and doctors have combined training?

PMID- 10076224
TI  - The future face of medical training--ship-shape and Bristol fashion.

PMID- 10076225
TI  - Reflection and nursing knowledge.

PMID- 10076226
TI  - Research focus. The appropriateness of nursing models for theatre nurses.

PMID- 10076227
TI  - Surgical gowns and drapes into the 21st century.
AB  - According to the MDD (Medical Devices Directive) 93/42/EEC of 13 June 1993,
      medical products including gowns and drapes must provide a high level of
      protection for patients, users and others. The European Commission CEN/TC 205/WG
      14, under the leadership of its convenor, Professor Werner, is developing a
      mandatory European standard on the basic requirements and test methods for
      disposable and reusable materials for protection of patients, surgical personnel,
      and operating room facilities i.e. gowns and drapes. This European standard is
      intended to clarify the situation with respect to products and their properties,
      defining basic requirements, for users and manufacturers of medical products.
      Future use of standard cotton textiles and conventional cotton-polyester mixed
      textiles is uncertain as they may not meet the requirements of the new standard,
      i.e. resistance to penetration by microbiological microorganisms, liquids and
      particle release. However, there are innovative reusable barrier surgical drapes
      and gowns which meet the basic requirements of the standard made from liquid
      repellent micro-filament materials, material laminates and perhaps some specific
      cotton polyester materials which have been chemically modified. In the new
      standard based on CEN/TC 205/WG 14, quality assurance for reprocessing of
      surgical gowns and drapes is critical. The manufacturer/distributor must use
      validated processes to prove that the requirements of this European Standard are
      met. Quality Assurance Systems will be required to give proof of decontamination,
      disinfection and sterilisation. Specified processes are to be used to maintain
      the properties of the materials throughout reprocessing. It is the responsibility
      of the hospital to assure optimal protection of patients and users. In case of a
      lawsuit, this could lead to the burden of proof being shifted to the hospital,
      with related risk of liability because it is always assumed that the work is
      being done according to the 'state of the art'. Difficult situations arise when
      it must be proved that one has acted equivalent to or better than the standard
      procedures and that no mistakes are made. Because of this risk of liability
      alone, the question of what surgical materials are used in the future should be
      considered very carefully.

PMID- 10076228
TI  - The history and application of homeopathy and today's patients.

PMID- 10076229
TI  - The column on politics with a small 'p'.

PMID- 10076230
TI  - The efficacy of oral analgesia for postoperative pain.
AB  - The aims of this study were to assess the efficacy of acute pain management for
      the postoperative patient, identify analgesic requirements and to ascertain the
      incidences of side effects, if any. One important observation noted from the
      study was that there were quite a significant number of patients that were
      receiving more that one analgesic on a regular basis. The implications of multi
      prescription without strict controls could have a profound negative effect on
      patient health. Although side effects were noted to be higher in the group of
      patients that received multiple analgesics, no patient suffered any detrimental
      or long term effects, and in general patients did appear to be satisfied with
      their analgesic regime.

PMID- 10076231
TI  - A short course in anaesthetic nursing: a case study.

PMID- 10076232
TI  - Audit of consent forms.

PMID- 10076233
TI  - Your learning needs: enlisting your manager's help.

PMID- 10076234
TI  - Reflecting on experiential and management knowledge.

PMID- 10076235
TI  - CE mark. What's that?

PMID- 10076236
TI  - An aid to recruitment? Evaluation of the NATN perioperative nursing video.

PMID- 10076237
TI  - Charter Mark--Orsett day unit.

PMID- 10076238
TI  - Clinical effectiveness: practical solutions for the new agenda.

PMID- 10076239
TI  - The column on politics with a small 'p'.

PMID- 10076240
TI  - A rose by any other name...

PMID- 10076241
TI  - Two must reads.

PMID- 10076242
TI  - Evaluating nurses' knowledge and patients energy intake after intervention.
AB  - The aims of this study were to describe and assess nutritionally at-risk
      patients' energy intake and nurses' knowledge and opinions of patients' need of
      energy during their hospital stay, before and after training and education. The
      effects of the intervention were evaluated by using a questionnaire, answered by
      the nurses before and after the intervention, and indirectly by measuring the
      patients' nutritional outcome, using a nutritional assessment form. A total of
      230 matched patients and 171 nurses (86 before the intervention and 85 after)
      participated in the study. After the education, results indicated that a greater
      number of patients received increased levels of energy intake, an increased
      average intake of energy, and more dietary supplements. Nurses' knowledge about
      the content of energy in a standard portion of food had increased, and they found
      it easier to assess patients' need of energy. After the education, more nurses
      had the opinion that well-educated nurses in nutrition make it easier to motivate
      patients to reach a sufficient intake of energy.

PMID- 10076243
TI  - The theory is the practice: an exemplar.
AB  - The centerpiece of this article is an exemplar of an elderly woman who makes a
      startling revelation to a clinical nurse specialist who is making a consultative
      home visit related to a physical condition. The exemplar illustrates the uniquely
      powerful contribution of the nurse work of intentionality, presencing, mutuality,
      knowing, and caring in helping patients to heal. Newman's theory of Health as
      Expanding Consciousness provides the framework for a paradigm shift from a
      curative to a healing practice of nursing.

PMID- 10076244
TI  - Defining a place for clinical nursing research in the spheres of CNS influence.

PMID- 10076245
TI  - Research utilization and the CNS: confronting the issues.
AB  - Utilization of research in nursing is still inconsistent despite nearly two
      decades of published models and studies on the subject, and of leaders urging
      that the profession must increase its use of research. In fact, several questions
      regarding research utilization in nursing remain unanswered. A review of selected
      models of research utilization is presented, as well as a review of the published
      studies of utilization barriers and facilitators. Three key questions for the
      profession as a whole and for the clinical nurse specialist (CNS) in particular
      are advanced, and concrete answers for the practicing CNS are offered.

PMID- 10076246
TI  - Case managing heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) and its two subtypes, early onset (Type I)
      and delayed onset (Type II), are becoming an increasing concern in acute care.
      Also called "white clot syndrome," this condition can lead to thrombosis and loss
      of limb. Alternatives to heparin therapy, such as low molecular weight heparin,
      are discussed as ways to decrease HIT. An algorithm has been developed to guide
      identification and monitoring of patients at risk for HIT. The article presents
      the expanded role of the clinical nurse specialist as case manager in clinically
      managing patients with actual or potential HIT. The case manager's role for
      patients receiving heparin lies in increasing the awareness of this condition
      among all clinicians and serving as a resource for current information regarding
      its prevention, diagnosis, and treatment.

PMID- 10076247
TI  - More on Medicare reimbursement: clarification of direct billing and "incident to"
      billing.

PMID- 10076248
TI  - Research collaboration: harder than it should be, better for nursing.

PMID- 10076249
TI  - An advanced practice nurse--nurse researcher collaborative model.
AB  - The advanced practice nurse (APN)--nurse researcher collaborative model proposed
      in this article emerged through an APN and a nurse researcher working together on
      a pilot research study and a project to describe advanced nursing practice in the
      outpatient setting. The model demonstrates how, through the observation and
      discussion of practice and research, the needs of both the NR and the APN are
      identified. Further discussion identifies outcomes important for each
      professional role as well as for the discipline of nursing. Results of such
      collaboration include practice-relevant nursing research, research-based
      practice, and more reflective APNs and nurse researchers.

PMID- 10076250
TI  - Nursing education: the ball is in the professionals' field.

PMID- 10076252
TI  - [Test-your knowledge] [In Process Citation]

PMID- 10076251
TI  - [Monitoring a patient with continuous epidural perfusion].

PMID- 10076253
TI  - [Professional exhaustion, a concept to be clarified].

PMID- 10076254
TI  - [The survivor syndrome. Heading for new ground].

PMID- 10076255
TI  - [Taking care of the caregiver and the patient].

PMID- 10076256
TI  - [Microwave oven and health care: caution!].

PMID- 10076257
TI  - [The patient with multiple trauma in the emergency unit. A challenge for the
      nurse].

PMID- 10076258
TI  - [A nurse plunged into the realities of street children].

PMID- 10076259
TI  - External change and its impact on nurse management: a case study.
AB  - AIMS: This paper sets out to identify major changes in the tasks and
      responsibilities of the nurse manager at a small postgraduate unit in central
      London as it and its parent hospital group became subject to major changes in the
      policy and financial environment. What happened to the nurse manager's function
      could well make transparent some of the important changes still affecting nurse
      management more generally today. BACKGROUND: The article adds to the somewhat
      meagre academic literature which considers the middle management role in nursing.
      METHODS: The paper is based on a single yet detailed case study and the data were
      gathered by one of the authors over the period of change. The pros and cons of
      the dual researcher/participant role need to be considered along with the
      possibly wider significance of the case study. FINDINGS: The overriding
      conclusion is that nurse management in the specialist unit is evolving from a
      classic bureaucratic mode in which managerial authority, information and decision
      making were highly centralized to a much more devolved set of arrangements.
      Clearly a host of factors--e.g. the culture and history of the organization, and
      the personality types of the key players--could affect such change. However, this
      article concentrates on showing how the earlier, more centralized style was
      increasingly problematic in the rapidly changing circumstances faced by the unit.
      CONCLUSIONS: In understanding the wider significance of this particular case
      study, it seems important to understand the strengths and weaknesses of the
      methodology. If such changes in nurse management are widespread, they represent a
      new era for nursing in action and one perhaps more consonant with a profession
      whose status is being enhanced by developments such as diploma and graduate
      education and the development of specialist roles.

PMID- 10076260
TI  - Our healthier hospital? The challenge for nursing.
AB  - AIM: This paper aims to explore the problems which are currently preventing
      hospital nurses from fulfilling their health promotion role, and makes
      recommendations for nursing managers. BACKGROUND: Hospital nurses have a key role
      to play in meeting recent Government proposals, which aim to enhance health
      promotion and public health in the NHS. KEY ISSUES: Lack of knowledge and skills,
      unhealthy hospital environments, poor collaboration, insufficient time and poor
      nursing management are impediments to hospital nurses promoting health.
      CONCLUSIONS: Hospital nurse managers need to capitalize on government enthusiasm
      by supporting health promotion education for nursing staff improving the hospital
      environment and facilitating better interdisciplinary working.

PMID- 10076261
TI  - Patient satisfaction: a key concept for evaluating and improving nursing
      services.
AB  - AIMS: The main purpose of this review was to explore the meaning of patient
      satisfaction and present the theoretical background and the definitions which
      developed in nursing. BACKGROUND: Today, there is an increasing interest in
      patient satisfaction which is considered a valid indicator of the quality of
      care. ORIGINS OF INFORMATION: An extensive literature review was performed by
      using the MEDLINE database. DATA ANALYSIS: Data was classified and analysed by
      using the content analysis approach. KEY ISSUES: The principal finding of this
      review was the lack of attention to the meaning of patient satisfaction, the
      development of theoretical frameworks and the psychometric properties of the
      developed instruments. CONCLUSIONS: Nurses need to develop valid and reliable
      instruments to measure patient satisfaction in order to improve the quality of
      care and make their work visible.

PMID- 10076262
TI  - An investigation into the functions of nurses' communication at the inter-shift
      handover.
AB  - AIMS: This study set out to investigate the functions of nurses' communication at
      the inter-shift handover. BACKGROUND: The inter-shift handover should facilitate
      continuity in care by transferring patient information between shifts. However,
      nurses may also use this time for team building. METHODS: An observational study
      was conducted during six inter-shift handovers occurring on one ward in a general
      hospital in the UK. The data was transcribed and a thematic analysis applied.
      FINDINGS: The main themes related to the transfer of patient information and team
      building, the strongest theme being team building. Nurses were found to
      communicate goals and values relating to nursing practice so facilitating
      cohesiveness of the nursing team. CONCLUSIONS: The nursing ritual of inter-shift
      handover serves the purpose of enhancing a shared value system amongst nurses. It
      should therefore not be regarded as an outdated means of communication.

PMID- 10076263
TI  - A comparison of the career aspirations of degree and P2000 diploma graduates from
      UK nursing programmes.
AB  - AIM: This paper reports the findings from a study of career aspirations
      undertaken as part of a larger study on the graduate outcomes of two different
      preregistration nursing educational programmes in the UK. METHODS: A self
      completion questionnaire was administered to 52 degree graduates and 28
      diplomates from two Universities on completion of their course. FINDINGS: The
      findings suggest that while graduates appeared more definite over their long-term
      career goals, diplomates were more confident in their initial decision to enter
      the nursing profession. All respondents showed a marked tendency towards hospital
      based clinical posts on graduation. Degree graduates displayed a greater interest
      in working overseas, nominating a far broader range of possible destinations and
      expressed interest in a wider range of further education courses, including
      Master's and PhD degrees. CONCLUSIONS: The career aspirations of degree graduates
      and diplomates revealed in this study highlight a number of issues with
      implications for workforce planning, recruitment and retainment. Further larger
      scale longitudinal research is warranted.

PMID- 10076264
TI  - Chronic pain and distress among elderly in the community: comparison of patients'
      experiences with enrolled nurses' assessments.
AB  - AIM: This study compared elderly patients' reported experiences of pain and
      distress with enrolled nurses' assessments and related potential differences to
      patient and enrolled nurse characteristics. BACKGROUND: Many elderly suffer from
      chronic pain but few studies have focused on this group of patients. METHODS:
      Data were collected through personal interviews with 38 patients and
      questionnaires completed by 38 enrolled nurses. FINDINGS: Enrolled nurses
      underestimated patients' experiences of physical pain, physical discomfort,
      breathing problems, resignation, and dependency. Pain and distress were
      overestimated by enrolled nurses who had lower scores on three of the five
      personality scales used. In contrast, enrolled nurses who had higher scores on
      these personality scales tended to underestimate the patients' pain and distress.
      CONCLUSIONS: There is a need to develop staff training programmes in order to
      optimize the care for elderly patients with chronic pain in the community.

PMID- 10076265
TI  - Equity and rationing in the NHS: past to present.
AB  - AIM: This paper explores the historical and political basis of equity and
      rationing in the British National Health Service (NHS). BACKGROUND: Rationing has
      always featured in the NHS as an implicit, rather than explicit process. Recent
      healthcare reforms have highlighted the inequity of healthcare provision in the
      UK and made the rationing debate more explicit. ORIGINS OF INFORMATION:
      Information is drawn from a variety of sources which include research studies,
      review articles and books, policy documents and personal experience of working in
      the NHS. KEY ISSUES: The search for efficiency in the new NHS is in conflict with
      the principle of equity and the most vulnerable groups in society are being
      denied access to healthcare. Decisions about rationing are currently made at a
      local rather than a national level resulting in variability of health service
      provision, an inconsistency which will continue with the development of primary
      care groups. CONCLUSIONS: Rationing of healthcare resources is thought to be
      inevitable as demands for healthcare increase in a funds-limited service.
      Rationing of resources is a political problem that requires some form of guidance
      from central government.

PMID- 10076266
TI  - Prerequisites for quality improvement in nursing.
AB  - AIM: This study examines how the characteristics of nurses, working communities
      and leadership affect the prerequisites for quality improvement in nursing.
      BACKGROUND: Knowledge of the phenomena affecting nurses' action is needed, since
      quality of care is seen as a result of an individual carer's professional skills,
      work motivation and commitment to work. METHODS: Material for the study was
      collected using a questionnaire. The respondents were 723 nursing practitioners
      from two special level hospitals. The main instrument used was the Managerial
      Abilities instrument developed by the researchers. FINDINGS: The results of the
      statistical analyses showed that exhaustion experienced by the nurses is the most
      important obstacle to quality improvement in nursing. The education of nurses,
      good team work and the ward sister's managerial abilities have a positive
      influence on quality improvement in nursing. CONCLUSION: Nurses' exhaustion
      should be reduced in order to improve quality of care.

PMID- 10076267
TI  - The nurse manager as a professional-managerial class: a case study.
AB  - AIM: This study set out to capture the work dynamics and impact of nurse managers
      during healthcare restructuring. BACKGROUND: The nurse managers are instrumental
      to healthcare reform in which the ultimate goal is the promotion of a cost
      effective healthcare delivery system. METHODS: A case study approach was used.
      Interviews were conducted with 12 nurse managers working in an acute hospital in
      Hong Kong. The data was analysed initially by thematic analysis, followed by the
      extended case method. FINDINGS: This study showed that the coalition of the nurse
      and manager role gives rise to the professional-managerial class (PMC). These
      nurse PMCs enjoyed the kind of power, job satisfaction and work autonomy that
      frontline nurses did not experience. They managed nurses who predominantly
      occupied the workforce and managed nursing care that composed the main bulk of
      work in hospital service. CONCLUSIONS: The emergence of a group of nurse managers
      is essential to a cost-effective service, and to maximize nursing efforts in
      healthcare.

PMID- 10076268
TI  - Clinical exemplars describing expert staff nursing practices.
AB  - AIM: This study was undertaken to identify and describe expert staff nursing
      practices in a large teaching hospital in south-western USA. BACKGROUND:
      Differentiation of the skill level of staff nurses is important for assuring
      safe, quality care. In the current atmosphere of corporate, downsizing, shortened
      hospital stays, cross training and continued high staff nurse turnover rates, it
      is of critical importance to identify and describe the essential contributions of
      expert nursing practice and to recognize and reward nurses according to their
      skill level. METHOD: Clinical situation interviews and participant observations
      were conducted using the interpretative phenomenological research approach.
      Narrative data were obtained and analysed systematically in multiple stages to
      identify and describe recurring meanings, themes, exemplars and constitutive
      patterns. FINDINGS: The final stage of data analysis involved interpretation of
      the narrative text using Benner's (1984) 'domains and competencies of nursing
      practice' as a framework. These competencies were validated in this study and 16
      new competencies were identified. CONCLUSIONS: Expert staff nursing practices
      described in this project are not behaviours commonly defined as organizational
      expectations in performance appraisals for staff nurses. These practices need to
      be incorporated into position descriptions, performance appraisals and clinical
      ladders to recognize, foster and acknowledge the significance of expert nursing
      practice.

PMID- 10076269
TI  - Implementation of a self-scheduling system: a solution to more than just
      schedules!
AB  - AIM: To describe a model of self-scheduling and the systematic process involved
      in its implementation on a nursing unit in an American hospital. BACKGROUND: A
      change in staff work schedules became necessary when staff dissatisfaction,
      absenteeism, vacancies and staffing costs increased. The approach used to tackle
      these issues resulted in other significant outcomes such as staff-initiated
      projects to improve care and more time for the manager to address other issues.
      FINDINGS: When staff managed the project, dissatisfaction, absenteeism and costs
      decreased. A modified version of the self-scheduling model was replicated for
      other units. The gap between management and staff narrowed and staff utilized the
      process as a continuing education project. Applications to work on the unit
      multiplied. However, complaints of peer pressure, favouritism and unavailability
      of staff on certain shifts also emerged. CONCLUSION: Moving work environments to
      become more employee-friendly can facilitate transformation. Incentives to
      attract staff and respect for the needs of staff can translate to improved care
      for external customers. Recommendations are made concerning the need for nurse
      managers to be employee-sensitive in the interests of productivity, staff
      retention and progress.

PMID- 10076270
TI  - A comparison between patients' experiences of how their caring needs have been
      met and the nurses' patient classification--an explorative study.
AB  - AIM: To examine whether patient classification carried out in accordance with the
      Oulu Patient Classification (OPC) method can measure the patient's caring needs
      in a reliable manner as seen from the patient's perspective. BACKGROUND: On the
      basis of earlier research it can be established that there are differences
      between nurses' and patients' assessments of patients' caring needs. Research on
      patients' assessments of perceived caring needs and the care they receive in
      connection with patient classification does not seem to have interested
      researchers in caring science. METHODS: The reliability from the patient's
      perspective is gauged by comparing the patient's perceived caring needs with the
      nurse's patient classification during a 24-h bed-day. Data was collected during a
      semi-structured interview with a total of 73 patients. Documentary analysis was
      carried out on the basis of patient classifications by 30 ward nurses. FINDINGS:
      On the basis of the degree of correspondence between nursing care intensity
      experienced by the patients and the nurses' patient classification it was decided
      whether the patients' caring needs had been met. The results indicate, however,
      that patient classification as a gauging method has a built-in reductive function
      regarding the patient's need for care and nursing care intensity. CONCLUSIONS:
      Nevertheless the OPC offers possibilities from a patient perspective of providing
      an overall picture of the patient's nursing care intensity and can therefore
      serve as a reliable basis for decisions concerning staff planning.

PMID- 10076271
TI  - The tao of professional appraisal: how to remain content and calm during the
      appraisal interview.
AB  - AIM: This paper sets out to investigate the theories and practices of healthcare
      appraisal systems, with particular emphasis on the appraisal of healthcare
      educators. BACKGROUND: The rhetoric used to inform appraisal theories, systems
      and practices claims to measure human attributes, although this is rarely
      achieved in reality. METHOD: A national survey of healthcare educators is used to
      inform, analyse and evaluate the literature pertaining to professional appraisal
      theories and systems. FINDINGS: The main theme to emerge centres around the
      inadequacies of current appraisal systems and practices. CONCLUSION: Nurse
      educators and healthcare professionals should be creative and proactive in their
      approaches to the appraisal process, to enable more effective and meaningful
      appraisal processes and outcomes.

PMID- 10076272
TI  - Some reflections on cultural and social considerations in mental health nursing.
AB  - This article critiques the contribution of two main theoretical perspectives on
      mental health care and ethnicity, with particular reference to Asian women. It
      considers the work of those who highlight the impact of culture on the health and
      illness experience (Kleinman 1980, Rack 1982, Fernando 1989) and the work of
      authors who argue that the impact of broader socio-economic structures must be
      considered (Donovan 1989, Pearson 1989, Ahmad 1993). It is posited that the
      emphasis on cultural difference results in crude monolithic generalizations about
      Asian culture and operates as a smokescreen for the impact of poverty and racism.
      The backdrop to this article is provided by an assessment of the problematic
      conceptual framework of Western mental health and the role it plays in
      perpetuating stereotypes. It is concluded that mental health nurses need a
      thorough understanding of the complexity of the cultural and social factors that
      influence health and illness; an understanding which falls somewhere between
      these two theoretical perspectives. Such an approach needs to be grounded in the
      experience of mental health clients themselves if it is to be appropriate.

PMID- 10076273
TI  - Developing user involvement in mental health services.
AB  - This paper describes the user consultation component of a corporate approach to
      the mental health needs assessment of a local population. The context of the
      paper is established by presenting the views of users and user representatives on
      current mental health services. This is followed by the development of
      participants' views of an 'ideal' mental health service within the boundaries of
      technical feasibility. Three focus groups were held with current service users,
      and one group with user representatives. The users have extensive experience of a
      range of mental health services. The findings suggest that user representatives
      tend to represent their own needs rather than those of users. It would also seem
      that service users are not a homogeneous group, different groups having different
      priorities. Overall, users' views of current services generally reflect previous
      studies, but the 'ideal' approach seems to broaden the discussion and identify an
      agenda for change. This agenda is framed within categories of service delivery,
      service providers, labelling, advocacy, future research, leaving services,
      involvement, co-ordination, information, choice and accessibility. There is no
      clear role specifically identified for mental health nurses by users, but many
      opportunities are highlighted. Exploration of the utility of co-operative inquiry
      between mental health nurses and service users is recommended.

PMID- 10076274
TI  - Psychiatry at the front line: CPNs working outside regular hours in an inner-city
      A&E department.
AB  - This paper reports on a study that examines the characteristics of patients with
      mental health problems, seen outside regular working hours, by CPNs working
      within an in an inner-city A&E department. The study examined the range of
      presenting problems for each individual attendance rather than the primary
      diagnosis or main presenting problem. There were significant differences in the
      pattern of presentations between patients with and without a mental health
      professional (MHP) involved in their care. Patients with a MHP involved in their
      care were much more likely to present with psychosis and suicidal ideation in the
      absence of deliberate self-harm. Those without a MHP were much more likely to
      have deliberately harmed themselves, to have interpersonal problems, to have
      misused alcohol or drugs or to have work/financial problems. The CPNs worked in
      an autonomous manner and appeared to reduce the intensity of the duty
      psychiatrists' workload by filtering out patients judged not to be in need of
      their specialist input.

PMID- 10076275
TI  - A survey of psychiatric nurses' opinions of advanced practice roles in
      psychiatric nursing.
AB  - This postal survey established psychiatric nurses' opinions of the content of
      advanced practice psychiatric nursing roles. A random sample, consisting of 100
      members of the Network for Psychiatric Nursing Research (NPNR), was surveyed. 78%
      returned completed questionnaires. Responses were analysed using the chi-square
      test, and the Mann-Whitney U-test. Elements of the normal nursing role identified
      included psychiatric assessment, patient and carer education, and basic
      psychotherapeutic practices. Identified advanced practice roles included
      psychiatric diagnoses, prescribing single emergency doses and modifying doses of
      a wide range of psychotropic medication. Enhanced autonomy in admission and
      discharge and additional powers under the Mental Health Act were also supported.
      The prescription of full courses of medication and the prescription and
      administration of electroconvulsive therapy were rejected as nursing roles.
      University and Trust employed nurses responded differently in a number of these
      areas. The study concluded that an advanced practice role which incorporates
      restricted elements of psychiatric practice is supported by psychiatric nurses,
      and recommends that pilot sites should be established which test the
      acceptability and effectiveness of the identified role.

PMID- 10076276
TI  - Research methods in clinical investigation: a case study analysis of medication
      levels and self-harm.
AB  - This paper uses a case study to illustrate an application of the scientist
      practitioner model to clinical practice. Through consultation with a clinical
      psychologist, a simple method of obtaining an objective overview of the
      therapeutic use of medication was developed. Focusing on a woman in a Regional
      Secure Unit, data were gathered from incident forms of self-harm and the
      corresponding drug charts. Using basic statistical techniques (such as
      frequencies and measures of central tendency) to summarize these data, useful
      clinical information was obtained. Actual data from the case study are presented,
      as an example of a research process that can be applied to understanding the role
      of extraneous variables when pursuing a course of chemical treatment. Analyses of
      drug effects suggest that additional variables such as environmental,
      interpersonal and engagement factors needed to be considered. The paper advocates
      the ease of applicability of research methods to clinical investigation.

PMID- 10076277
TI  - Semi-structured and unstructured interviewing: a comparison of methodologies in
      research with patients following discharge from an acute psychiatric hospital.
AB  - This comparison of interview methods was made during a preliminary investigation
      into the experiences and expectations of patients discharged from an acute
      psychiatric hospital. The data was collected by four unstructured and four semi
      structured interviews and included the views of respondents regarding the method
      used. A comparison of both interview methods was made. Analysis followed Miles &
      Huberman's (1994) guidance for data analysis, from which conclusions were drawn.
      Data were first reduced, then displayed using cross-case analysis. The use of
      Miles & Huberman's (1994) model of data analysis proved effective in allowing for
      data to be displayed and compared in a robust manner. Findings related to the
      comparative analysis showed that unstructured interviews resulted in greater
      depth and enabled positive and negative aspects of care to be identified in
      greater detail than semi-structured interviewing. Additionally, when asked to
      reflect upon the interview methods used, respondents found that unstructured
      interviewing allowed them to describe their experiences and expectations in
      greater detail than semi-structured interviews.

PMID- 10076278
TI  - Admission trends to a special hospital: court diversion and prison transfers.
AB  - This paper reviews the literature regarding the diversion of mentally disordered
      offenders from the criminal justice system to the mental health services, with a
      specific focus on the high security psychiatric special hospitals. The
      traditional sources of admission to these institutions have been predominantly
      courts and prisons, with the majority of patients being admitted via the former
      route. This study reports on the admissions to a special hospital over a 20-year
      period, and shows that over the previous decade there has been a reversal in this
      trend, with the number of patients transferred from prison being greater than
      that via any other route. The factors that may have contributed to this reversal
      are discussed and conclusions are drawn as to the external and internal forensic
      factors that may influence the court's decision in the referral process.

PMID- 10076279
TI  - Consideration of three arenas of social control for the treatment and management
      of sexual offenders.
AB  - This paper sets out to explore the influences of social control upon the
      discourse relating to treatment and management of sexual offenders. This
      discussion takes as its foci three environmental arenas (social, penal/judicial
      and health care), and examines their influences and culpability within this
      context. It is not the intention of this article to present, nor does it arrive
      at, any answers to the perpetual concerns of treatment and management of this
      offender group, preferring to leave it to the individual reader to draw their own
      conclusions. It is accepted that there is no gender demarcation amongst sexual
      offenders, though in this paper, the masculine tense is used.

PMID- 10076280
TI  - Chronically mentally ill individuals re-entering the community after
      hospitalization.
AB  - The purpose of this phenomenological study was to increase the understanding of
      the experiences of chronically mentally ill individuals who are re-entering the
      community after hospitalization. Ten individuals from an acute care psychiatric
      hospital who had had two or more admissions within a 12-month period were
      interviewed, shortly before discharge and subsequently between two and four times
      while in the community. Three interrelated themes emerged. First, at the time of
      discharge, the optimism of the participants about returning home was tempered by
      a realistic recognition of their problems. As time passed, their problems seemed
      to become their preoccupying focus and optimism faded. Second, for most of the
      participants, relationships with others, positive, negative or both, played an
      important role in their return to home and community. Third, participants who
      experienced more positive social relationships also described individual
      achievements and community involvement. The re-entry process was not a smooth
      transition for these individuals.

PMID- 10076281
TI  - 'I wanted to be a nurse ... but I didn't get that far': women with serious
      ongoing mental health problems speak about their lives.
AB  - Within mental health services there are fewer women than men with serious mental
      health problems and there is evidence that their needs are relatively neglected
      resulting in specific deleterious effects. In research, as in services, the
      abilities of women with serious mental health problems appear to be under
      estimated, and there is almost a total absence of research into the views and
      experiences of such women. This study aimed to explore the lives of women with
      serious ongoing mental health problems and their experience of services, to
      develop understanding of the context and impact of mental distress. In a series
      of 5 focus group interviews, the women, who were using a range of services for
      people with long-term mental health problems, described lives which, even before
      the onset of mental health problems, were marked by material, social and personal
      disadvantage. Their mental health problems led to numerous losses: loss of homes,
      jobs, relationships, children and loss of 'normality', yet the women retained
      hopes and aspirations for the future. The women clearly identified aspects of the
      service that they valued, in particular the support and company of women workers
      and other women service users. The implications of these findings are discussed
      in relation to planning and providing mental health services for women.

PMID- 10076282
TI  - Family coping with mental illness: a comparative study.
AB  - Two studies were conducted by the same researcher, one in Canada, the other in
      Japan, looking at families' reactions to their relatives' mental illness. The
      focus was placed on family caregivers' transformation processes, which are a
      unitary process of pattern appraisal and deliberate mutual patterning based on a
      unitary transformative paradigm within Newman's theory of health as expanding
      consciousness.

PMID- 10076283
TI  - Perceptions of adolescents living with parental alcoholism.
AB  - The purpose of this study was to explore and understand the experience of
      parental alcoholism from an adolescent's perspective. The stories of five
      adolescents were used to generate descriptions and explanations about the
      phenomenon. The study was exploratory in nature and was conducted using a
      qualitative research design. Data were collected by means of in-depth interviews
      with each adolescent. Field notes, personal reflections, and transcripts of all
      interviews made over the course of the research process, constituted the data for
      analysis. Four significant themes emerged from the data, which illuminated and
      provided a fuller understanding of the perceptions of adolescents living with
      parental alcoholism. The initial theme, 'The Nightmare', described the
      adolescents' memories and what it was like for them growing up with parental
      alcoholism. The second theme, 'The Lost Dream', explored their recognition of
      loss in terms of the experiences of the nightmare. The third theme, 'The
      Dichotomies', explained the daily struggles between what the adolescents thought,
      what they felt, and how their thoughts and feelings influenced their behaviour.
      The fourth theme, 'The Awakening', described the adolescents' recognition of
      their present responsibilities, and their understanding about their pasts, which
      enabled them to begin to let go and move on. The study concludes with reflections
      on the significance, meaning, and interrelatedness of the identified themes, and
      a discussion of findings and implications. The main findings were the resilience
      and strength of the participants, the uniqueness of each of their stories, and
      the therapeutic benefit to the participants from the opportunity to tell their
      stories. An understanding of the individual and contextual nature of adolescents'
      perceptions of parental alcoholism provides professional caregivers with new
      opportunities to offer specialized services to adolescents and their families.

PMID- 10076284
TI  - The healing process, the road to recovery and positive mental health.
AB  - This paper is designed to explore and examine the experience of loss following a
      hysterectomy. The painful aftermath of the ordeal and the work involved in the
      healing process are outlined and discussed from both a personal and professional
      perspective. The manuscript highlights a number of inner struggles that had to
      negotiated before an equilibrium in mental health and wellbeing was successfully
      achieved. The forces that move the dialogue forward from one theme to the other
      are complex in their simplicity. The enigmatic dimensions of physical pain and
      emotional torment are expressed and worked through in a sensitive and intimate
      manner. The mysteries of internalized, conflicting messages on socialization
      issues, such as gender roles and living in and identifying with only one culture
      are discussed and debated. In addition, the disharmony between spiritual ideals,
      the meaning and purpose of life, the process of self-actualizing and the physical
      realities involved in living are identified and elaborated upon. Embroidered
      within the tapestry of the text is the need to revisit the curriculum for the
      education and training of mental health nurses to enhance the quality and
      provision of effective, humane and therapeutic nursing care.

PMID- 10076285
TI  - Social dancing: a way to support intellectual, emotional and motor functions in
      persons with dementia.
AB  - Dementia causes serious impairments and the inability to perform those activities
      which give meaning to a person's life. Therefore, these persons are in need of
      professional nursing care interventions as well as a special supporting
      environment. In this study, social dancing has been regarded as a nursing
      intervention that supports persons with dementia in nursing home settings. The
      aim was to find out how persons with dementia functioned in social dance
      sessions, in order to understand the reasons behind the use of social dancing as
      a nursing intervention in a nursing home setting. Six persons with dementia were
      videotaped during four dance sessions in one nursing home. The qualitative
      content analyses were carried out deductively, using a guide developed from the
      variables in the Gottfries, Brane and Steen rating scale (GBS scale). The
      findings show that, for persons with dementia, retained abilities were prominent
      in dancing. It was obvious that social dancing was supportive and seemed to have
      meaning to both patients and their carers. Social dancing seems to be a nursing
      intervention that supports patients' positive feelings, communication and
      behaviour. The carers' preunderstanding of the patients' levels of dementia and
      the wholeness of the situation was of importance.

PMID- 10076286
TI  - Mental illness and Irish people: stereotypes, determinants and changing
      perspectives.
AB  - The causes of psychological illness in Irish people have been identified with
      colonial rule and the catastrophic conditions deriving from famine in the
      nineteenth century. In particular, the scourge of unremitting emigration,
      resulting from famine, has formed a background against which speculative theories
      of inferiority, alienation and mental illness have been constructed. In
      particular, the long standing idea that Irish people exhibit higher rates of
      schizophrenia, both in Ireland and abroad, is discussed. Contemporary studies
      which suggest that these elevated rates do not correspond to international
      diagnostic criteria for schizophrenia are introduced. Rather, these enhanced
      rates may reflect a malaise which resembles schizophrenia but which is really a
      product of historical dispossession. The importance of these factors is
      underscored by the previous neglect of Irish people, considered as an ethnic
      minority, as well as the particular distaste which many Irish people display
      towards such a notion.

PMID- 10076287
TI  - Shared meanings for military nurse veterans: follow up survey of nurse veterans
      from WWII, Korea, Vietnam, and Operation Desert Storm.
AB  - This study is an extension of a qualitative study involving military nurses in
      World War II, Korea, Vietnam and Operation Desert Storm. Common themes and shared
      meanings identified in the previous qualitative study were investigated using a
      broad sample of military nurses who had served at various times and different
      branches of the service. The present investigation used a survey to gather data,
      and results tended to validate results of the earlier study that the experiences
      of military nurses in times of war tend to transcend many factors including time
      and branch of service.

PMID- 10076288
TI  - A review and synthesis of the literature: the use of presence in the nursing care
      of families.
AB  - With the current emphasis on cost-consciousness in health care, nurses must re
      examine resources that may already exist yet are underutilized in the provision
      of care for patients. Two such resources, the nurse's use of her or his presence
      as a therapeutic process in stimulating patients' healing and the contributions
      of patients' families to care delivery, are frequently overlooked. This paper
      critically reviews the literature regarding presence with a focus on the
      relevance of this caring behavior to family-centered nursing. Conceptual and
      practice knowledge gaps are identified and implications for future research are
      indicated.

PMID- 10076289
TI  - Pulmonary rehabilitation: is it cost effective?
AB  - The purpose of the study was to evaluate number of hospitalizations, length of
      stay, exercise routine, and patient satisfaction following attendance at a
      pulmonary rehabilitative program. A retrospective chart review and survey
      conducted on 72 subjects with chronic obstructive pulmonary disease showed a
      significant decrease in number of hospitalizations and length of stay following
      attendance at the program. In addition, 72% of the subjects continued to carry
      out an exercise routine and 99% indicated that the rehabilitation program had met
      their expectations. This study suggests that the pulmonary rehabilitative program
      was cost-effective.

PMID- 10076290
TI  - Empowering staff nurses to participate in the American Nurses Association's call
      for quality indicators research.
AB  - The American Nurses Association (ANA) advocates establishment of a national
      database, which can collect, aggregate, and analyze patient data to link nursing
      activities to 10 quality of care outcomes. These outcomes, developed through
      extensive research, can highlight the essential nature of nursing, demonstrate
      institutional compliance with external standards, and justify registered nurse
      staffing patterns. Staff nurses collect and record the data that provide the
      foundation for the quality nursing indicators research initiative. This paper
      focuses on the important and unique role that staff nurses can play in advancing
      this agenda.

PMID- 10076291
TI  - [Patient counseling. Apprenticeship for patients].

PMID- 10076292
TI  - [It can not be taught theoretically. Touch].

PMID- 10076293
TI  - [Discussion about active assistance in dying. Is there a right to quick easy
      death?].

PMID- 10076294
TI  - [Short stories. A time to mature].

PMID- 10076295
TI  - [Prone position in respiratory insufficiency. Prone ventilation].

PMID- 10076296
TI  - [Caring for a patient at home at the end of his life. "I have to catch a
      train..."].

PMID- 10076297
TI  - [I have AIDS--I want to die at home].

PMID- 10076298
TI  - [Helping others at the expense of one's own health].

PMID- 10076299
TI  - [Travel to foreign countries. A diploma in one's pocket].

PMID- 10076300
TI  - [The pressure to save time].

PMID- 10076301
TI  - [Seeking the meaning of suffering and death] [In Process Citation]

PMID- 10076302
TI  - [Loving care and hard budgets].

PMID- 10076303
TI  - [Frau Muller really should be in a nursing home].

PMID- 10076304
TI  - [Caring--helping the other to grow].

PMID- 10076305
TI  - [Case management. The nurse as care manager].

PMID- 10076306
TI  - [Conference of European AIDS-care societies. A milestone in Swiss nursing.
      Interview by Monika Brechbuhler].

PMID- 10076307
TI  - [Advice for patients. Apprenticeship for patients].

PMID- 10076308
TI  - [Letting go. Changing one's outlook].

PMID- 10076309
TI  - [Conference of EANAC. A phase in Swiss nursing]

PMID- 10076310
TI  - [Between passion and compassion, an art of living].

PMID- 10076311
TI  - [Patients' rights. There is nothing vague in nursing practice].

PMID- 10076312
TI  - [The sickness prolongs the leave] [In Process Citation]

PMID- 10076313
TI  - [The large power of family women].

PMID- 10076314
TI  - Quality of care in reproductive health programmes: monitoring and evaluation of
      quality improvement.
AB  - As 200 million women become pregnant every year, at least 30 million will develop
      life-threatening complications requiring emergency treatment at any level of
      society where they live. But it is a basic human right that pregnancy be made
      safe for all women as complications are mostly unpredictable. This requires
      reproductive health programmes which are responsive to women's and their
      families' needs and expectations on the one hand and enhancement of community
      participation, high quality obstetric services, and both provider collaboration
      and satisfaction on the other. Monitoring and evaluation of these facets need to
      be an integral part of any safe motherhood programme, not only to assess
      progress, but also to use this information for subsequent planning and
      implementation cycles of national programmes. Lessons learned from ten years'
      implementation of Safe Motherhood programmes indicate that process and outcome
      indicators are more feasible for short-term evaluation purposes than impact
      indicators, such as maternal mortality reduction. The former are described in
      this paper with relevant country examples. This is the third, and last, article
      in a series on quality of care in reproductive health programmes. The first
      (Kwast 1998a) contains an overview of concepts, assessments, barriers and
      improvements of quality of care. The second (Kwast 1998b) addresses education
      issues for quality improvement.

PMID- 10076315
TI  - Continuity of carer and satisfaction.
AB  - OBJECTIVE: To study the association between continuity of carer and satisfaction
      with antenatal, intrapartum and postpartum domiciliary care. DESIGN: A
      descriptive study comparing satisfaction measures between women cared for by a
      known or unknown midwife. Data on satisfaction were extracted from the
      intervention group of a birth centre trial, and the names of the individual
      carers from two clinical databases kept at the birth centre. SETTING: An in
      hospital birth centre in Stockholm. SUBJECTS: 410 women who had been randomly
      allocated to birth centre care during pregnancy, and who had a normal vaginal
      delivery at the centre. Complete data, including the names of the caregivers and
      the women's satisfaction scores, were available in 175 cases (43%) during the
      antenatal episode, 404 cases (98%) during the intrapartum episode and in 254
      cases (62%) during the episode of postpartum domiciliary care. MAIN OUTCOME
      MEASURES: Overall satisfaction with antenatal care, intrapartum care, labour and
      birth, and postpartum domiciliary care. FINDINGS: No statistical differences were
      observed in satisfaction with antenatal care between women who had seen only one,
      two, or more than two midwives at their check-ups during pregnancy; in
      satisfaction with intrapartum care or the birth itself when comparing women who
      were delivered by a known or unknown midwife; or in satisfaction with domiciliary
      care when the midwife was known or unknown. CONCLUSION: The findings suggest that
      continuity of carer is less important in a birth centre. The high levels of
      satisfaction in women having birth centre care were probably more affected by the
      attitudes of the carers, the philosophy of care, and the nice and calm
      environment than by knowing the individual midwife well.

PMID- 10076316
TI  - Team midwifery: the views and job satisfaction of midwives.
AB  - OBJECTIVE: As part of an evaluation of a team midwifery scheme we assessed the
      satisfaction of community and hospital midwives and their views about working
      practices and care provided. DESIGN: Survey of complete enumeration of community
      midwives (most working in teams) and hospital midwives providing antenatal,
      intrapartum and postnatal care to a population of women. SETTING: Community and
      district general hospital, in the UK. MEASUREMENTS: Socio-demographic data about
      midwives, ratings on Likert-type scales of job satisfaction, quality of care
      variables, relationships with other professionals and women; Glasgow Midwifery
      Process Questionnaire. FINDINGS: 80 out of 92 midwives (87%) responded. Community
      midwives were younger, more recently qualified, employed on lower grades, less
      likely to be married and have children than hospital midwives. The Glasgow
      Midwifery Process Questionnaire revealed that midwives, particularly hospital
      midwives, had low morale. Community midwives were more likely to report that
      their job was satisfying, offered a variety of work, enabled them to use skills
      and knowledge fully, and offered opportunities for professional development.
      Hospital midwives were more likely to report following strict guidelines.
      Community midwives, however, disliked the long on call and unsociable hours, and
      reported disruption to family/social life. Forty-one per cent of hospital
      midwives (12) and 28% of community midwives (14) reported regularly working
      beyond their shift. Whilst midwives thought that team midwifery was, in theory, a
      good idea, in practice it was not working well because of the size of teams and
      caseload. About half the community midwives felt that teams had detrimentally
      affected the quality and continuity of care. CONCLUSIONS: Whilst team midwifery
      aims to improve continuity of maternity care, in this instance, it does not
      appear to achieve this aim. Many midwives reported it had adversely affected
      care. Team midwifery is a source of disillusionment for midwives, since the
      continuity of carer ideal is unachievable in a system based on teams of seven or
      more. Attendance at the delivery may be a luxury provided at the expense of
      antenatal and postnatal continuity. IMPLICATIONS: Midwives recommended remedial
      measures: reducing team sizes, reducing caseloads, ensuring teams were fully
      staffed, reducing 'on call' and labour ward hours. It remains to be seen whether
      these will have the desired effects on continuity of care.

PMID- 10076317
TI  - Disclosure of disability: exploring the perspective of parents.
AB  - OBJECTIVE: To explore the perspective of parents with regard to disclosure of
      disability and early follow-up care. DESIGN: The research approach was
      hermeneutic phenomenology. Data were collected using focused interviews that were
      audio-taped, transcribed and interpreted. SETTING: Scotland. PARTICIPANTS: The
      parents of 63 children born with a congenital limb deficiency. FINDINGS: The
      findings demonstrate the complexity and variability in parental response.
      Additionally, what is shown is that disclosure was often handled poorly and that
      the support offered during the stay in the maternity unit was frequently
      inadequate. CONCLUSION: In order to handle disclosure effectively, health
      professionals require appropriate education and training and it is recommended
      that innovative ways of encouraging discussion and debate are sought.

PMID- 10076318
TI  - Constructing a home birth environment through assuming control.
AB  - OBJECTIVE: The purpose of this qualitative study was to describe the experience
      of couples who have had a home birth. DESIGN, SETTING AND PARTICIPANTS: A
      phenomenological approach was used to provide an understanding of the human
      experience of home birth in Western Australia. The research design consisted of a
      field study, in which 10 parent couples were interviewed and three videos of home
      births observed. Of the ten couples, four couples spoke of their first baby's
      home birth and the remaining six couples had three or four children who had been
      born at home. FINDINGS: The couples' experiences of home birth were gained
      through identifying significant statements from transcripts and field notes, and
      clustering these into the following four themes: 'constructing the environment';
      'assuming control'; 'birthing'; and 'resolving expectations'. The themes of
      'constructing the environment' and 'assuming control' are described in detail in
      this paper. 'Constructing the environment' describes how couples adapted the
      physical environment, and established support to create a positive birth
      environment. 'Assuming control' discusses exerting control and taking
      responsibility for the birth. The remaining themes of 'birthing' and 'resolving
      expectations' are described in a subsequent paper (Morison et al, in press). KEY
      CONCLUSIONS: The research furnishes an insight into the couples' experience of
      home birth. The lived experience of birthing at home involved a process where a
      couple actively created an environment that enabled them to assume control and
      responsibility for the birth. IMPLICATIONS FOR PRACTICE: The findings are
      important for midwives in any setting, as they reveal the extent to which some
      parents value the right to assume control and responsibility for the birth of
      their baby. Although the physical environment of a home birth cannot be
      replicated in every setting, issues specific to the birth environment are
      relevant to all midwives.

PMID- 10076319
TI  - What influences the uptake and early cessation of breast feeding?
AB  - OBJECTIVE: To examine obstetric, maternal and social factors associated with the
      uptake and early cessation of breast feeding and women's reasons for altering
      from breast to bottle feeding. DESIGN: Women who responded to a postal
      questionnaire on long-term postpartum health were contacted and asked to
      participate in a home-based interview. In addition to health problems, the
      interview obtained information on baby feeding and a number of social factors.
      Women were also asked to complete the Edinburgh Postnatal Depression Scale
      (EPDS). Obstetric and maternal data were obtained from maternity records.
      SETTING: Deliveries from a large maternity hospital in Birmingham. PARTICIPANTS:
      906 women were interviewed at a mean of 45 weeks after delivery. FINDINGS: 63% of
      the women said they had breast fed, but 40% of these stopped within three months
      of delivery. Many of the women gave physical problems with lactation as reasons
      for stopping. The factors found to be predictors of early cessation were: return
      to work within three months of birth; regular childcare support from other female
      relatives, and a high EPDS score. Non-initiation of breast feeding was predicted
      by a different set of factors: multiparity; general anaesthetic (GA); and
      unmarried status. DISCUSSION AND CONCLUSION: Despite evidence of the benefits of
      breast feeding, this remains an unacceptable long-term option for many women, and
      for over one-third it is never attempted. Factors within the woman's social
      environment were found to influence early cessation. Women who had a GA during or
      immediately following labour and delivery were less likely to initiate breast
      feeding. IMPLICATIONS FOR PRACTICE: If breast-feeding incidence and duration are
      to increase, more attention should be paid to establishing early, successful
      breast feeding and countering the negative influences of factors within the
      social environment.

PMID- 10076320
TI  - Women's perceptions of birth plans.
AB  - OBJECTIVE: To investigate the use and effects of birth plans and how women
      perceive them. DESIGN: Retrospective questionnaire survey. SETTING: A teaching
      hospital with approximately 3000 deliveries per annum in Dundee, Scotland.
      PARTICIPANTS: 143 primigravidae, six to 13 weeks following delivery. FINDINGS:
      The study achieved a 71% response rate. Ninety per cent of women had completed a
      birth plan. Most women thought the process of completion of the plan had been
      useful by allowing discussion of available options beforehand. Half said the
      birth plan did not make any difference to the amount of control they felt during
      labour, although many thought that not enough attention had been paid to what
      they had written. Most women said they would make another birth plan in a future
      pregnancy. CONCLUSIONS: The majority of women found completion of a birth plan
      was beneficial. IMPLICATIONS FOR PRACTICE: More attention should be paid to the
      birth plan by carers during labour.

PMID- 10076321
TI  - The views of women of above average weight about appropriate weight gain in
      pregnancy.
AB  - OBJECTIVE: To examine the beliefs of women of above average weight about
      appropriate levels of weight gain in pregnancy. DESIGN: An in-depth qualitative
      study of 37 women. SETTING: Women recruited from a city hospital, a rural
      hospital and by community midwives in the south of England. PARTICIPANTS: Women
      were identified via hospital notes or by community midwives. Over a one-year
      period all women identified who attained the weight of 90 kg by the 30th week of
      pregnancy were eligible to participate. The sample comprised 37 women. The sample
      was varied in terms of age, social class, household composition and number of
      children. MEASUREMENT: Two in-depth interviews were carried out with each
      interviewee: during late pregnancy and six weeks following childbirth. FINDINGS:
      Interviewees were concerned not to weigh more after pregnancy than before. Their
      perceived ability to control weight gain during pregnancy was varied. In the
      perceived absence of specific advice from health professionals, they constructed
      their own views about appropriate levels of weight gain. These were informed by
      their desire to minimise weight gain and to provide adequate nourishment for the
      growth and development of their baby. Comments and advice from health
      professionals were interpreted within the women's own understandings of
      appropriate levels of weight gain. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      (1) the desire to return to their pre-pregnancy weight was a strong motivating
      factor among pregnant women of above average weight, but some women lacked
      confidence in their ability to control weight gain; (2) the health and well-being
      of their unborn baby is often a central concern in women's decisions about
      appropriate weight gain; (3) health professionals need to explore the beliefs of
      women of above average weight about appropriate weight gain in pregnancy; and (4)
      written information about weight gain may assist women of above average weight in
      understanding what might be an appropriate level of weight gain during pregnancy.

PMID- 10076322
TI  - The development of a problem-based curriculum in midwifery.
AB  - Making use of best available evidence has clearly become an important part of
      midwifery practice. As educational programmes are preparing the practitioners of
      the future, it is believed that midwifery education should also be informed by
      evidence. At Thames Valley University, a BSc Midwifery curriculum, using the
      principles of problem-based learning, has been implemented following a review of
      both appropriate research and evaluation. This article explains the process
      undertaken in preparation for the course as well as the proposed means of ongoing
      evaluation.

PMID- 10076323
TI  - Mental health and medicine: cultural considerations in treating Asians.

PMID- 10076324
TI  - Colonel Margaret E. Bailey: first black nurse to be promoted to colonel in U.S
      Army Nurse Corps.

PMID- 10076325
TI  - PCGs: community nursing's hope for the future.

PMID- 10076326
TI  - Healthcare delivery in the 21st century: preparing for practice.

PMID- 10076328
TI  - Making inferences from data.

PMID- 10076327
TI  - Tempting GNVQ health and social care students to the world of nursing.

PMID- 10076329
TI  - Evaluating mentor performance.

PMID- 10076330
TI  - Evaluating healthcare strategy.

PMID- 10076331
TI  - Working in expanding roles.

PMID- 10076332
TI  - Surveys reveal nurses getting the message about PREP.

PMID- 10076333
TI  - Understanding statistics. 3. Statistical tests: continuous data.

PMID- 10076335
TI  - Planning an evaluation study and collecting information.

PMID- 10076334
TI  - Partnerships for sound practice.
AB  - Our research into clinical supervision is continuing and project members are
      disseminating clinical supervision throughout the organisation. Evaluation
      clearly shows that at least 25% of registered nurses are already engaged in
      clinical supervision. There are no distinct clinical areas that have not
      supported staff members participating in the project, indicating its widespread
      acceptance. In addition, we have discovered that staff with the least prior
      experience of clinical supervision, such as school nurses and health visitors,
      are committed to its practice. Clinical supervision is no longer seen as the
      preserve of mental health nurses. The project is enhancing relationships at all
      levels between nurses. Service development and rigorous research have been
      closely linked, while, for individual nurses, continuing professional development
      is offering a pathway to academic qualification.

PMID- 10076336
TI  - Independent consultants.

PMID- 10076337
TI  - Returning to practice: will this be another millennium bug?

PMID- 10076338
TI  - Education for practice. Tests for categorical data.

PMID- 10076339
TI  - Community care services: the future framework.

PMID- 10076340
TI  - Complementary therapies: who uses them?

PMID- 10076341
TI  - Networking for career planning.
AB  - Formal networking approaches should be prepared for meticulously. If you waste
      your contact's time waffling around a subject, you may find that the person is
      not so willing to talk with you another time. Have your questions ready, be as
      specific as you can, and be businesslike. And remember, no one can wave a magic
      wand and have a solution to all your queries. You should not expect anything from
      informal networking situations--if you do, you will give out unconscious signals
      that might put people off. Just enjoy yourself, meet new people, share ideas and
      thoughts, and maybe you will be able to help them or they will be able to help
      you in the future. Your career is in your own hands--but others are often willing
      to lend a hand.

PMID- 10076343
TI  - Moving up, but not far enough.

PMID- 10076342
TI  - What's the evidence? Clinical effectiveness.
AB  - This learning unit explores how to find and appraise evidence from clinical
      information, and how to apply it to effective and appropriate clinical practice.
      The aim of the unit is to give nurses an understanding of the role of evidence in
      achieving clinical effectiveness, and to identify how nurses can find and make
      use of this evidence in their own practice.

PMID- 10076344
TI  - Changing times ahead.

PMID- 10076345
TI  - Caring for conjoined twins.

PMID- 10076346
TI  - Putting it right.

PMID- 10076347
TI  - Waging war against bowel cancer.

PMID- 10076348
TI  - Visiting rights.

PMID- 10076349
TI  - Back to the future.

PMID- 10076350
TI  - Stress and the nurse.

PMID- 10076351
TI  - Talking the same language. Interview by Jenny Knight.

PMID- 10076352
TI  - Broadcast.

PMID- 10076353
TI  - Sustainable change.
AB  - In the first of a series of four reports, the author outlines the driving factors
      behind radical changes that took place in care delivery at Leicester Royal
      Infirmary. Future reports will focus on the nurses' role in change programmes,
      the importance of education in successful change and examples of process change
      in gynaecology and endoscopy.

PMID- 10076354
TI  - Innovation in general practice: a service for teenagers.
AB  - Offering healthcare services in primary care settings, wherever appropriate, has
      been the major focus of NHS development this decade (NHSE 1996). In this article,
      the authors discuss the setting up and running of a collaborative community youth
      health service, an innovation that targeted a neglected patient group in the
      community using facilitated workships.

PMID- 10076355
TI  - The role of the clinical nurse specialist.
AB  - Despite the prevalence of clinical nurse specialists, research suggests that
      their role remains poorly understood (O'Hanlan and Gibbon 1996). In practice,
      they fulfil a number of important roles linked to developing practice. Here, the
      author critically examines the range of roles the clinical nurse specialist may
      undertake and how they influence patient care.

PMID- 10076356
TI  - Favourite patients: exploring labelling in inpatient culture.
AB  - In this article, the author reports on a research study into the issue of
      favouritism in nursing, exploring theory relevant to the topic. The study focused
      on the nature of favouritism in nursing. Its explorative and descriptive nature
      allowed interviews to be conducted with nurses. They acknowledged that attachment
      and boundaries seem to be the most important issues related to favouritism.
      However, some of the participants pondered on the notion that personal
      characteristics of both patients and nurses affect the nature of nurse-patient
      interaction and attachment. The study has enabled discussion about these various
      aspects of practice and provides some tentative conclusions.

PMID- 10076358
TI  - Crisis? What crisis?

PMID- 10076357
TI  - Postnatal depression.
AB  - Postnatal depression encompasses childbirth mood disorders from the blues to
      serious psychiatric illness (DoH 1998b). Chris Bewley explains the variety of
      biological, psychological, cultural and sociological factors involved and how
      health professionals can be involved in preventing such disorders from becoming
      long-term depressive illness.

PMID- 10076359
TI  - Education: the shape of things to come.

PMID- 10076360
TI  - No vacancies.

PMID- 10076361
TI  - Close encounters.

PMID- 10076362
TI  - Welcome home.

PMID- 10076363
TI  - Still waiting.

PMID- 10076365
TI  - The great divide.

PMID- 10076364
TI  - Reaching out to child prostitutes.

PMID- 10076366
TI  - A different sort of nurse consultant.

PMID- 10076367
TI  - Hot summer in Iceland.

PMID- 10076368
TI  - Family nurses: Europe's future?

PMID- 10076369
TI  - Nursing and re-engineering.

PMID- 10076370
TI  - Reflective practice--using a learning journal.
AB  - Reflective practice learning journals have become a valued teaching and learning
      tool in nurse education, particularly for nursing students from other countries.
      Here, the author reflects on their use by overseas students as part of an overall
      strategy to ensure that cross-cultural education programmes are flexible and
      grounded in the realities of the cultural and healthcare context in which nursing
      and midwifery practice takes place. The article is based on personal experience
      and observations made while working with students from many different countries
      with different professional backgrounds.

PMID- 10076371
TI  - Healthcare students' attitudes to sunbathing.
AB  - The risks of exposure to the sun are now well known. But, as this study shows,
      nurses' education and their own attitudes and behaviour suggest they are not well
      prepared to convince patients and clients of the need to change behaviour.

PMID- 10076372
TI  - Fungal infections.

PMID- 10076373
TI  - Child support.

PMID- 10076374
TI  - A victory for working mothers everywhere.

PMID- 10076376
TI  - Working at Broadmoor.

PMID- 10076375
TI  - Mission impossible?

PMID- 10076377
TI  - Recovery time.

PMID- 10076378
TI  - Tucked up by the flu.

PMID- 10076379
TI  - Life after the China seize.

PMID- 10076380
TI  - Get ahead, get a nurse.

PMID- 10076381
TI  - He had a family and now James Trapp can't afford to be a nurse.

PMID- 10076382
TI  - People's learning experiences come from a variety of sources.

PMID- 10076383
TI  - New labour's problem.

PMID- 10076384
TI  - We need more than a wing and a prayer.

PMID- 10076385
TI  - Diana's legacy for life.

PMID- 10076386
TI  - Home is where the care is.
AB  - This article describes how a children's home care service operates as part of a
      general paediatric service within an acute NHS trust. Although a debate exists
      about whether a home care service should be set up as part of a community or
      acute trust, there are advantages and drawbacks for staff within either system.
      The authors believe that children benefit regardless of where the service is
      based.

PMID- 10076387
TI  - Words that wound.

PMID- 10076388
TI  - Credit.

PMID- 10076389
TI  - Hit the big time.

PMID- 10076390
TI  - Life gets a good site better.

PMID- 10076391
TI  - On the right road.

PMID- 10076392
TI  - NT/3M National Nursing Awards. Under new management.

PMID- 10076393
TI  - Open house.

PMID- 10076394
TI  - Screening for ovarian cancer: is it worth the risk?
AB  - New screening methods need to be fully evaluated to assess whether they should be
      introduced in the NHS. This article summarises a systematic review of research on
      screening for ovarian cancer. There is no evidence that screening reduces the
      death rate and there is the potential for significant harm from diagnostic
      surgery in women with false positive results. Screening should be done only
      within well-conducted research trials.

PMID- 10076396
TI  - Natural therapeutic holding.

PMID- 10076395
TI  - Obstacles to using a database in midwifery.
AB  - The increasing emphasis on evidence-based care poses a range of practical
      problems, not least of which is access to the information on which care is to be
      based. This article reports on a Scottish study that examined the impact of
      giving midwifery units access to the Cochrane pregnancy and childbirth database.
      The results suggest that installing the database had little effect on practice. A
      key issue was computer use. Although the midwives had a positive attitude towards
      computers, they did not feel they had the necessary skills to find information on
      the databases. Given that 70% of those questioned used computers regularly, the
      cause of their uncertainty is not clear.

PMID- 10076397
TI  - A nursing model of overdose assessment.
AB  - Assessing people following a suicide attempt is an opportunity for therapeutic
      intervention and for gathering essential information. This article outlines a
      nursing model for assessing people admitted to hospital following a drug
      overdose. The model is presented alongside a case study demonstrating its
      application in practice.

PMID- 10076398
TI  - More than skin deep.

PMID- 10076399
TI  - Wound care. And so to beds.

PMID- 10076400
TI  - Wound care. What a relief measure.

PMID- 10076401
TI  - Wound care. Vacuum wrapped.

PMID- 10076402
TI  - Giving a blanket bath--1.

PMID- 10076403
TI  - Nurse practitioners help to provide quality, cost-effective care to patients with
      cancer.
AB  - Since their role was conceived more than 30 years ago, nurse practitioners (NPs)
      have demonstrated their ability to provide effective, accessible, cost-effective
      health care for a range of primary healthcare services, including preventing
      illness, managing chronic illness, and treating minor episodic health problems.
      In recent years, the job market has increased for NPs in specialty areas, such as
      oncology, as physicians and medical administrators have recognized the quality
      and cost-effectiveness of the role.

PMID- 10076404
TI  - Describe one aspect of your job that best depicts the role of the oncology nurse
      practitioner.

PMID- 10076405
TI  - Nurse practitioners can find professional challenges and continuing-education
      opportunities on the Internet.

PMID- 10076406
TI  - 1997 Balanced Budget Act advances NP independence.

PMID- 10076407
TI  - [The new chairman of the county section of the Austrian Nursing Society is
      introducing herself].

PMID- 10076408
TI  - [The use of nursing personnel in endoscopy in Austria].

PMID- 10076409
TI  - [Language and communication as decisive factors in professional nursing].

PMID- 10076410
TI  - [Clinical picture: stroke. Patient-oriented discussion with stroke patients].

PMID- 10076411
TI  - [Communication within the nursing team].

PMID- 10076412
TI  - [Analysis of topics and collection of material. Continuation of the Didactic
      Series of the Osterreichische Krankenpflegezeitschrift].

PMID- 10076413
TI  - [We have looked across the border. "Kinesthetic Infant Handling"].

PMID- 10076414
TI  - [Transcultural nursing].

PMID- 10076415
TI  - [Guidelines for decisions at the end of life].

PMID- 10076416
TI  - [Nursing requires respect for life, for the dignity and the basic rights of man].

PMID- 10076417
TI  - [Transcultural nursing/intercultural nursing].

PMID- 10076418
TI  - [Cultural dimensions of humane care--the Sunrise Model].

PMID- 10076419
TI  - [Prevention of burnout--raising the quality of leadership?].

PMID- 10076420
TI  - The new change process: always a work in progress.

PMID- 10076421
TI  - QUI contributes to cost-effective contented care.

PMID- 10076422
TI  - Caregiving: a woman's role.

PMID- 10076423
TI  - Cognitively impaired residents receive less pain medication than non-cognitively
      impaired residents.

PMID- 10076424
TI  - To be or not to be: the challenge of urinary continence in older adults.

PMID- 10076425
TI  - Get a second opinion, even if it's your own.

PMID- 10076426
TI  - Experiences of patients hospitalized during the Texas mental health scandal.
AB  - TOPIC: The impact of psychiatric hospitalization on children and adolescents
      hospitalized during the Texas mental health scandal. METHODS: Content analysis of
      archival data and in-depth interviews. FINDINGS: Subjects (N = 19) voiced
      complaints about the stigma resulting from the hospitalization as well as lack of
      individual care, violations of personal boundaries, ineffectual outcomes,
      permanent disruption to family relations, separation from family, trauma of
      seeing others restrained, and being restrained themselves. CONCLUSIONS:
      Unnecessary psychiatric hospitalization has long-term ramifications for children
      and adolescents in terms of self-view, family, and social relationships.

PMID- 10076427
TI  - Diagnosis and treatment of attention-deficit/hyperactivity disorder.
AB  - TOPIC: Diagnosis and treatment of attention deficit/hyperactivity disorder.
      PURPOSE: To describe a multidimensional approach to treatment of children with
      attention deficit/hyperactivity and their parents. SOURCES: Review of the
      literature and of the author's clinical work. CONCLUSIONS: A great deal of
      controversy surrounds this diagnosis. The nurse psychotherapist helps children
      and families through the diagnostic process and into the treatment phase.
      Emphasis is on psychotherapy of the child and family, parent education, and
      attention to the child's school environment and social adjustment.

PMID- 10076428
TI  - Cognitive therapy for the suicidal patient: a case study.
AB  - TOPIC: The use of cognitive therapy to treat a suicidal patient. PURPOSE: To
      demonstrate through the use of a case study, the cognitive therapy method in
      treating a suicidal patient. SOURCE: The author's own clinical work. CONCLUSION:
      Suicidal people often demonstrate perfectionism, social sensitivity, difficulty
      problem solving, and hopelessness. Cognitive therapy addresses these problems by
      helping patients plan activities, track destructive thinking and its impact on
      feelings and behaviors, and substitute constructive thinking, thus decreasing
      hopelessness.

PMID- 10076429
TI  - Sibling rivalry in nursing and the role of nurse psychotherapist.
AB  - TOPIC: The burgeoning role of the analytically prepared nurse psychotherapist in
      Great Britain. PURPOSE: To describe the struggles of nurses in this role and ways
      this struggle might be lessened. SOURCE: Observations of the author, an
      analytically prepared nurse psychotherapist-in-training in Great Britain.
      CONCLUSIONS: The role of the nurse psychotherapist with psychoanalytic training
      is in its infancy in Great Britain. Barriers to the development are both
      external, from outside the nursing profession, and internal, in the form of
      sibling rivalry or envy from less prepared nurses. Increased communication among
      nurses is encouraged so that a shared understanding and mutual respect may
      result.

PMID- 10076430
TI  - [Publicity work in social facilities: news is merchandise too].

PMID- 10076431
TI  - [German congress of the Society for Incontinence Care: counseling is a task for
      professional nurses].

PMID- 10076432
TI  - [The International Hartmann-Nursing Prize went to Belgium. The laureates
      impressed with their professional competence and creativity].

PMID- 10076433
TI  - [Congress on night care in Dusseldorf: insurance companies are expecting
      proposals from the nursing profession].

PMID- 10076434
TI  - [The federal statistics bureau presents its first health report: the development
      of nurses' incomes is lagging].

PMID- 10076435
TI  - [Meeting on nursing science and literature: awakening nurses' interest in
      theory].

PMID- 10076436
TI  - [First concerted action of the hospice movement: nurses are needed in pain
      therapy and for care of the dying].

PMID- 10076437
TI  - [Nursing standards in skin diseases. 3. Nurses apply various treatments. Nursing
      Standards in Dermatology work group].

PMID- 10076438
TI  - [50 years Pflegezeitschrift: guests on Christmas].

PMID- 10076439
TI  - [Modern bandaging techniques: what are transparent dressings all about?].

PMID- 10076440
TI  - [Healing touch in nursing: sensitizing one's hands].

PMID- 10076441
TI  - [Measuring blood pressure: are automatic devices easing the nurses' work?].

PMID- 10076442
TI  - [Ten days as a patient in a gynecology department. 2. There is loneliness behind
      the tears].

PMID- 10076443
TI  - [Experiences with a pedagogical project at the pediatric department: creating
      relaxation with music].

PMID- 10076444
TI  - [A German nursing student learned and worked in an American old-age home:
      American experiences for German nursing practice].

PMID- 10076445
TI  - [Questionnaires on childhood experiences of the elderly: on Saturday the family
      went to have a bath].

PMID- 10076446
TI  - [Standardized questioning in the Heidenheim district: comparing the quality of
      nursing homes].

PMID- 10076447
TI  - [The culture of the enterprise as a factor for success: the "us"-feeling is
      strengthened].

PMID- 10076448
TI  - [Living with the farewell. 2. Daring to admit helplessness].

PMID- 10076449
TI  - [Development of quality in the teaching of geriatric care: the curriculum has to
      be extended].

PMID- 10076450
TI  - [The wise women--living models for emancipatory care].

PMID- 10076451
TI  - Teach students what nursing really stands for--excellent patient care!

PMID- 10076452
TI  - Nursing's role and change: a challenge for the new millennium.

PMID- 10076453
TI  - Domestic violence in the workplace.

PMID- 10076454
TI  - Laser resurfacing: a survey of pre- and postprocedural care.
AB  - Laser resurfacing is fast becoming one of the most popular aesthetic procedures
      performed today. Techniques and equipment being used are undergoing rapid change.
      The patient desiring cosmetic surgery today has an active lifestyle with many
      commitments and responsibilities. Because of the needed healing time and initial
      appearance during the first week after laser resurfacing, the postoperative
      recovery period has been a major constraint when an individual is faced with
      making the choice for this procedure. These patients demand as little "down"
      time, or "out-of-sight" time as possible. Due to this identified need, a
      descriptive survey was done to gather information on practices performing laser
      resurfacing and the care to the patient before and after the procedure.

PMID- 10076455
TI  - Rare facial clefts: craniofacial anomalies.
AB  - Craniofacial surgery is an integrated approach to correct anomalies that include
      a range of deformities in the growth of the cranium and facial bones. The goal of
      surgery is to achieve a maximum result with the best possible functional and
      aesthetic results with minimal scarring in the least amount of time.

PMID- 10076456
TI  - Research in plastic surgical nursing.
AB  - This article discusses nursing research, its goals, and nurses' roles and
      responsibilities in the research process. A major focus of the article describes
      the concept of research utilization as an integral part of professional nursing
      practice. Implications for plastic surgical nursing practice and research
      activities with the American Society of Plastic and Reconstructive Surgical
      Nurses, Inc. (ASPRSN) are explored.

PMID- 10076457
TI  - Rule #1: Don't reinvent the wheel.
AB  - These are the things we recommend to speed the process along: Ask for input from
      key decision makers at the outset. Ask for input from the people who will be
      using the form, particularly patients. Highlight on the revised form the content
      that is different from the previous version. This way it is quicker for the
      decision-makers to read and they don't have to rehash what is already
      successfully in use. "Hand-walk" the form from person to person to obtain
      approval signatures. There are few things that are worse to lose in interoffice
      mail!

PMID- 10076458
TI  - Understanding informed consent.
AB  - Understanding and facilitating the informed consent process is our duty as
      perioperative nurses. Acting as patient advocates, we must determine if our
      patients have given "informed consent" prior to surgical treatment. When we
      witness our patients signing consent forms, we must be sure they are competent to
      sign; that they have spoken with the physician and have discussed the proposed
      procedure (including the risks, benefits and alternative treatments) and have had
      their questions answered; and have read the consent form they are being asked to
      sign. As nurses, we must become aware of our responsibilities related to informed
      consent. By understanding the concept of informed consent and its legal
      implications, we will be able not only to the facilitate informed consent process
      but also to fulfill our legal responsibilities.

PMID- 10076459
TI  - Ethical implications of organ transplantation.

PMID- 10076460
TI  - [December 1st, the worldwide AIDS day].

PMID- 10076461
TI  - [Nursing: organization, functions, and efficacy].
AB  - This article analyzes the defining traits of primary health care: length,
      accessibility, integrity, and coordination/continuity while bearing in mind the
      influence which these traits have on the organizational purpose of nursing. The
      evolution of nursing is also studied as it relates to the various reform phases
      in primary health care: the impulse phase and the implementation phase. A few
      aspects of this article were presented at the IV Primary Health Care Nursing
      Meeting which took place in Murcia.

PMID- 10076462
TI  - [Advantages and disadvantages of analgesia during childbirth].
AB  - Analgesia during childbirth is a right which should be at the disposal of every
      woman who desires it. Adequate pain control may reduce maternal anxiety and thus
      help make childbirth become a more satisfactory procedure. The parenteral
      administration of meperidine and epidural anesthesia are the most utilized types
      of obstetrical analgesia. Each of these two has its advantages as well as some
      secondary effects to bear in mind. Meperidine is very easy to administer;
      however, meperidine affects the degree of maternal consciousness and produces
      neonatal depression. On the other hand, epidural anesthesia has stronger
      analgesic power and does not interfere in the maternal-child relationship;
      however, it increases the risk of difficulties during childbirth. These secondary
      effects are the counterweights to consider when deciding whether or not to
      administer analgesia and if so, which kind.

PMID- 10076463
TI  - [Nursing in the movies: its image during the Spanish Civil War].
AB  - INTRODUCTION: The cinema had carried out a determining role in the development of
      stereotypes and in a wide gamut of models related to real life situations. The
      objective of this analysis is to determine the influence cinema had on the image
      of nurses during the Spanish Civil War from 1936-1939. These are the initial
      hypotheses: the role of Spanish nurses during the civil war was reflected by both
      sides in their respective movie productions; and the image of nurses shown in
      these films, on both sides, presents a conflicting role concept for women in
      society. METHODS AND MATERIALS: Following strategies developed by specialists in
      film analysis (Bondwell 1995, Uneso 1995, Carmona 1991) a total of 453 movie
      productions, 360 on the republican side and 93 on the national side, were
      reviewed. These films were listed in the Spanish National Films Library records.
      RESULTS: After analyzing the Spanish cinema productions during the Spanish Civil
      War, data relating to 453 films were identified. The genre included documents,
      news programs and fiction movies. 77 were produced in 1936, 235 in 1937, 102 in
      1938 and 39 in 1939. A tremendous difference exists between the republican
      productions, 79% of the total, and the national productions. By genres, the types
      produced on the republican side were: in 1936, 53 documentals, 4 news programs
      and 9 fiction films; in 1937, 186 documentals, 5 news programs and 19 fiction
      films; in 1938, 72 documentals, 1 news programs and 2 fiction films; in 1939, 2
      documentals and 2 fiction films. On the national side, their productions were: in
      1936, 10 documentals and 1 fiction film; in 1937, 22 documentals, 2 news programs
      and 1 fiction film; in 1938, 19 documentals and 3 news programs; in 1939, 29
      documentals and 6 fiction films. CONCLUSIONS: During the Spanish Civil War,
      movies produced by both sides made an effort to reflect their ideal woman as a
      stereotypical ideal nurse. This ideal nurse showed the values, ideas, aesthetics
      and prejudices each side held in the war.

PMID- 10076464
TI  - [The Gimbernat University Nursing School].

PMID- 10076465
TI  - [There exists a high percentage of hidden incontinence].

PMID- 10076466
TI  - [Caregivers for the world. Nursing and cooperation in the non-government
      organizations for development].

PMID- 10076467
TI  - [Health education. Experiences with nursing students].

PMID- 10076468
TI  - [Monitoring of anesthesized patients].

PMID- 10076469
TI  - [Tendons of the index finger and tendon links].

PMID- 10076470
TI  - [Treatment of chronic skin ulcers in the elderly. Descriptive study on the use of
      a hydrocellular dressing].
AB  - INTRODUCTION: There are a wide variety of products to use to treat skin ulcers.
      Knowing the correct usage and application of each product aids in choosing the
      most appropriate for elderly patients. OBJECTIVE: To evaluate the use of a
      hydrocellular dressing and its clinical test results. METHODS AND MATERIALS: This
      descriptive, prospective study begun on 6/X/97 and finished on 1/XII/97 included
      all the moderate or severely oozing skin ulcers, those classified as stage II,
      III, or IV, among the elderly at a home for them. This study discarded ulcers
      which barely bled; however, regional or systemic infection-related ulcers were
      included. RESULTS: 20 skin ulcers were analyzed. At the start, these covered an
      average surface are of 11.76 cm2 (DT 14.44), with an average severity index of
      23.79 (DT 35.81). At the end of this study, the average area was 7.92 cm2 (DT
      12.11) and the average severity index was 14,60 (DT 27,18). 7 ulcers, or 35%, had
      epithelized completely. During the 768 day length of this study, 290 dressings
      were applied. 100% of these were evaluated as easy to apply and remove; patients
      indicated an absence of pain; no dressing was disjoined when changed and
      therefore left no residue in the injured area. CONCLUSIONS: The dressing studied
      is effective for local treatment of all types of skin ulcers, regardless of their
      condition; this dressing reduces the number of changes necessary, especially in
      curing oozing ulcers; and finally, this dressing is easy to apply and aids in
      keeping the patient in good spirits.

PMID- 10076471
TI  - [Testing the usefulness of relaxation techniques in drug addicts. Proving its
      usefulness].
AB  - Experience in a hospital detoxification unit teaches that one of withdrawal
      symptoms which produces the greatest anxiety for a patient is sleeping disorders,
      whether insomnia or difficulty starting sleep. Both cause anxiety as bedtime
      approaches. This article stresses the importance of relaxation techniques for
      this type of patient when they are admitted in our detoxification unit. These
      techniques form part of accepted methods which our unit employs.

PMID- 10076472
TI  - [Nitroglycerin patches: properties and norms for correct use].
AB  - The frequent application of Nitroglycerin Transdermal Systems in patients who
      need a prophylaxis of anginal episodes requires that medical section should know
      to use them and their pharmacological properties. These knowledges about their
      application should be explained to patients and their relatives clear and
      concisely for them to achieve an accurate use. Having checked the required
      bibliography, I want to show in this article both the characteristics of this
      pharmacological preparation and some important points about educational process
      that patients and relatives should follow: at the same time, this article tries
      to answer all the questions which might arise.

PMID- 10076473
TI  - Antioxidant vitamins and cardiovascular disease: Dr Jekyll or Mr Hyde?

PMID- 10076474
TI  - Cardiovascular disease and risk factor epidemiology: a look back at the epidemic
      of the 20th century.

PMID- 10076475
TI  - A tale of 3 tails.

PMID- 10076476
TI  - Community-level interventions are needed to prevent new HIV infections.

PMID- 10076477
TI  - Prevalence and social correlates of cardiovascular disease risk factors in
      Harlem.
AB  - OBJECTIVES: This study examined the prevalence, social correlates, and clustering
      of cardiovascular disease risk factors in a predominantly Black, poor, urban
      community. METHODS: Associations of risk factor prevalences with sociodemographic
      variables were examined in a population-based sample of 695 men and women aged 18
      to 65 years living in Central Harlem. RESULTS: One third of the men and women
      were hypertensive, 48% of the men and 41% of the women were smokers, 25% of the
      men and 49% of the women were overweight, and 23% of the men and 35% of the women
      reported no leisure-time physical activity over the past month. More than 80% of
      the men and women had at least 1 of these risk factors, and 9% of the men and 19%
      of the women had 3 or more risk factors. Income and education were inversely
      related to hypertension, smoking, and physical inactivity. Having 3 or more risk
      factors was associated with low income and low education (extreme odds ratio [OR]
      = 10.2, 95% confidence interval [CI] = 3.0, 34.5 for education; OR = 3.7, CI =
      1.6, 8.9 for income) and with a history of unstable work or of homelessness.
      CONCLUSIONS: Disadvantaged, urban communities are at high risk for cardiovascular
      disease. These results highlight the importance of socioenvironmental factors in
      shaping cardiovascular risk.

PMID- 10076478
TI  - Evidence for a black-white crossover in all-cause and coronary heart disease
      mortality in an older population: the North Carolina EPESE.
AB  - OBJECTIVES: This cohort study evaluated racial differences in mortality among
      Blacks and Whites 65 years and older. METHODS: A total of 4136 men and women
      (1875 Whites and 2261 Blacks) living in North Carolina were interviewed in 1986
      and followed up for mortality until 1994. Hazard ratios (HRs) for all-cause and
      cause-specific mortality were calculated, with adjustment for sociodemographic
      and coronary heart disease (CHD) risk factors. RESULTS: Black persons had higher
      mortality rates than Whites at young-old age (65-80 years) but had significantly
      lower mortality rates after age 80. Black persons age 80 or older had a
      significantly lower risk of all-cause mortality (HR of Blacks vs Whites, 0.75;
      95% confidence interval [CI] = 0.62, 0.90) and of CHD mortality (HR 0.44: 95% CI
      = 0.30, 0.66). These differences were not observed for other causes of death.
      CONCLUSIONS: Racial differences in mortality are modified by age. This mortality
      crossover could be attributed to selective survival of the healthiest oldest
      Blacks or to other biomedical factors affecting longevity after age 80. Because
      the crossover was observed for CHD deaths only, age overreporting by Black older
      persons seems an unlikely explanation of the mortality differences.

PMID- 10076479
TI  - Potential explanations for the educational gradient in coronary heart disease: a
      population-based case-control study of Swedish women.
AB  - OBJECTIVES: This study examined the association between educational attainment
      and coronary heart disease (CHD) and the factors that may explain this
      association. METHODS: This population-based case-control study included 292 women
      with CHD who were 65 years or younger and 292 age-matched controls. RESULTS:
      Compared with the adjusted odds ratio for CHD associated with college education,
      the age-adjusted odds ratio associated with mandatory education (< or = 9 years)
      was 1.87 (95% confidence interval [CI] = 1.23, 2.84) and the odds ratio for high
      school education was 1.35 (95% CI = 0.81, 2.25) (P for trend < .01). The odds
      ratio for mandatory education was reduced by 82%, to 1.16 (95% CI = 0.69, 2.09),
      after adjustment for psychosocial stress, unhealthy lifestyle patterns,
      hemostatic factors, hypertension, and lipids. CONCLUSIONS: Much of the increased
      risk of CHD in women with low education appears to be linked to psychosocial
      stress and lifestyle factors. Hemostatic factors, lipids, and hypertension also
      contribute to a lesser extent. These factors may be considered in strategies
      geared to reducing socioeconomic inequalities in cardiovascular health.

PMID- 10076480
TI  - Is whole grain intake associated with reduced total and cause-specific death
      rates in older women? The Iowa Women's Health Study.
AB  - OBJECTIVES: This study sought to determine whether nutrient-rich whole grains
      reduce mortality risk. METHODS: The study included 38,740 Iowa women, aged 55 to
      69 years. A food frequency questionnaire was used to obtain data on grain intake.
      RESULTS: Median whole grain intake quintiles ranged from a median of 0.2 to more
      than 3 servings per day. Women with higher intakes had healthier lifestyles and
      less baseline disease. The total death rate decreased in increasing quintiles,
      and the pattern repeated for cancer, cardiovascular disease, and other causes
      combined. Adjusted for lifestyle and baseline disease, the relative hazard rate
      ratio for total death was about 0.85 in daily consumers of whole grain. Findings
      persisted in strata of baseline healthy and diseased and were not explained by
      dietary fiber. Rates of total mortality, but not cardiovascular disease
      mortality, were higher among frequent consumers of refined grain. CONCLUSIONS:
      Total mortality risk was inversely associated with whole grain intake and
      positively associated with refined grain intake. Refined grains contributed more
      than 20% of energy intake, and whole grains contributed 1%. Substitution of whole
      for refined grain may reduce chronic disease risk in the United States.

PMID- 10076481
TI  - Lead and hypertension in a sample of middle-aged women.
AB  - OBJECTIVES: The role of lead exposure as a risk factor for hypertension is less
      well defined among women than among men. This case-control study assessed the
      relation of blood and bone lead concentrations to hypertension in women. METHODS:
      Cases and controls were a subsample of women from the Nurses' Health Study.
      Hypertension was defined as a physician diagnosis of hypertension between 1988
      and 1994 or measured systolic blood pressure > or = 140 mm Hg or diastolic blood
      pressure > or = 90 mm Hg. RESULTS: Mean (SD) blood lead concentration was 0.15
      (0.11) mumol/L; mean tibia and patella lead concentrations by K-x-ray
      fluorescence were 13.3 (9.0) and 17.3 (11.1) micrograms/g, respectively. After
      adjustment for potentially confounding factors, an increase from the 10th to the
      90th percentile of patella lead values (25 micrograms/g) was associated with
      approximately 2-fold (95% confidence interval = 1.1, 3.2) increased risk of
      hypertension. There was no association between hypertension and either blood or
      tibia lead concentrations. CONCLUSIONS: These findings support a potentially
      important role for low-level lead exposure as a risk factor for hypertension
      among non-occupationally exposed women.

PMID- 10076482
TI  - Community-level HIV intervention in 5 cities: final outcome data from the CDC
      AIDS Community Demonstration Projects.
AB  - OBJECTIVES: This study evaluated a theory-based community-level intervention to
      promote progress toward consistent condom and bleach use among selected
      populations at increased risk for HIV infection in 5 US cities. METHODS: Role
      model stories were distributed, along with condoms and bleach, by community
      members who encouraged behavior change among injection drug users, their female
      sex partners, sex workers, non-gay-identified men who have sex with men, high
      risk youth, and residents in areas with high sexually transmitted disease rates.
      Over a 3-year period, cross-sectional interviews (n = 15,205) were conducted in
      10 intervention and comparison community pairs. Outcomes were measured on a stage
      of-change scale. Observed condom carrying and intervention exposure were also
      measured. RESULTS: At the community level, movement toward consistent condom use
      with main (P < .05) and nonmain (P < .05) partners, as well as increased condom
      carrying (P < .0001), was greater in intervention than in comparison communities.
      At the individual level, respondents recently exposed to the intervention were
      more likely to carry condoms and to have higher stage-of-change scores for condom
      and bleach use. CONCLUSIONS: The intervention led to significant communitywide
      progress toward consistent HIV risk reduction.

PMID- 10076483
TI  - The reach and effectiveness of a national mass media-led smoking cessation
      campaign in The Netherlands.
AB  - OBJECTIVES: This study examined the reach, effectiveness, and cost-effectiveness
      of a mass media-led smoking cessation campaign including television shows, a
      television clinic, a quit line, local group programs, and a comprehensive
      publicity campaign. METHODS: A random sample of baseline smokers (n = 1338) was
      interviewed before and after the campaign and at a 10-month follow-up. A
      nonpretested control group (n = 508) of baseline smokers was incorporated to
      control for test effects. RESULTS: Most smokers were aware of the campaign,
      although active participation rates were low. Dose-response relations between
      exposure and quitting were found. The follow-up point prevalence abstinence rate
      attributable to the campaign was estimated to be 4.5% after control for test
      effects and secular trends. The cost per long-term quitter was about $12.
      CONCLUSIONS: In spite of a massive rise in tobacco promotion expenditures prior
      to the campaign and the absence of governmental control over the media, the
      campaign under study may have increased normal cessation rates substantially.

PMID- 10076484
TI  - Radon and lung cancer: a cost-effectiveness analysis.
AB  - OBJECTIVES: This study examined the cost-effectiveness of general and targeted
      strategies for residential radon testing and mitigation in the United States.
      METHODS: A decision-tree model was used to perform a cost-effectiveness analysis
      of preventing radon-associated deaths from lung cancer. RESULTS: For a radon
      threshold of 4 pCi/L, the estimated costs to prevent 1 lung cancer death are
      about $3 million (154 lung cancer deaths prevented), or $480,000 per life-year
      saved, based on universal radon screening and mitigation, and about $2 million
      (104 lung cancer deaths prevented), or $330,000 per life-year saved, if testing
      and mitigation are confined to geographic areas at high risk for radon exposure.
      For mitigation undertaken after a single screening test and after a second
      confirmatory test, the estimated costs are about $920,000 and $520,000,
      respectively, to prevent a lung cancer death with universal screening and
      $130,000 and $80,000 per life-year for high risk screening. The numbers of
      preventable lung cancer deaths are 811 and 527 for universal and targeted
      approaches, respectively. CONCLUSIONS: These data suggest possible alternatives
      to current recommendations.

PMID- 10076485
TI  - Sexual harassment and generalized workplace abuse among university employees:
      prevalence and mental health correlates.
AB  - OBJECTIVES: This study hypothesized that interpersonal workplace stressors
      involving sexual harassment and generalized workplace abuse are highly prevalent
      and significantly linked with mental health outcomes including symptomatic
      distress, the use and abuse of alcohol, and other drug use. METHODS: Employees in
      4 university occupational groups (faculty, student, clerical, and service
      workers; n = 2492) were surveyed by means of a mailed self-report instrument.
      Cross-tabular and ordinary least squares and logistic regression analyses
      examined the prevalence of harassment and abuse and their association with mental
      health status. RESULTS: The data show high rates of harassment and abuse. Among
      faculty, females were subjected to higher rates; among clerical and service
      workers, males were subjected to higher rates. Male and female clerical and
      service workers experienced higher levels of particularly severe mistreatment.
      Generalized abuse was more prevalent than harassment for all groups. Both
      harassment and abuse were significantly linked to most mental health outcomes for
      men and women. CONCLUSIONS: Interpersonally abusive workplace dynamics constitute
      a significant public health problem that merits increased intervention and
      prevention strategies.

PMID- 10076486
TI  - Efficacy of Haemophilus influenzae type b conjugate vaccines and persistence of
      disease in disadvantaged populations. The Haemophilus Influenzae Study Group.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of
      Haemophilus influenzae type b (Hib) conjugate vaccines among children aged 2 to
      18 months and to determine risk factors for invasive Hib disease during a period
      of declining incidence (1991-1994). METHODS: A prospective population-based case
      control study was conducted in a multistate US population of 15.5 million. A
      laboratory-based active surveillance system was used for case detection. RESULTS:
      In a multivariate analysis, having a single-parent mother (odds ratio [OR] = 4.3,
      95% confidence interval [CI] = 1.2, 14.8) and household crowding (OR = 3.5, 95%
      CI = 1.03, 11.7) were risk factors for Hib disease independent of vaccination
      status. After adjustment for these risk factors, the protective efficacy of 2 or
      more Hib vaccine doses was 86% (95% CI = 16%, 98%). Among undervaccinated
      subjects, living with a smoker (P = .02) and several indicators of lower
      socioeconomic status were risk factors for Hib disease. CONCLUSIONS: Hib disease
      still occurs at low levels in the United States, predominantly in
      socioeconomically disadvantaged populations. Low immunization coverage may
      facilitate continuing transmission of Hib. Special efforts to achieve complete
      and timely immunization in disadvantaged populations are needed.

PMID- 10076487
TI  - What's driving an epidemic? The spread of syphilis along an interstate highway in
      rural North Carolina.
AB  - OBJECTIVES: The purpose of this study was to determine whether county syphilis
      rates were increased along Interstate Highway 95 (I-95) in North Carolina during
      a recent epidemic. METHODS: Ecological data on syphilis cases demographic data,
      highway data, and drug activity data were used to conduct a cross-sectional and
      longitudinal study of North Carolina countries from 1985 to 1994. Crude and
      adjusted incidence rate ratios (IRRs) were determined by means of standard and
      longitudinal Poisson regression models adjusted for sociodemographic factors and
      drug use. RESULTS: Ten-year syphilis rates in I-95 counties greatly exceeded
      rates in non-I-95 counties (38 vs 16 cases per 100,000 persons) and remained
      higher after adjustment for race, age, sex, poverty, large cities, and drug
      activity (adjusted IRR = 2.05, 95% confidence interval [CI] = 1.84, 2.28).
      Syphilis rates were stable until 1989, when rates increased sharply in I-95
      counties but remained stable in non-I-95 counties. Increased drug activity in I
      95 counties preceded the rise in syphilis cases. CONCLUSIONS: A better
      understanding of the relationship between high-ways and the spread of sexually
      transmitted diseases may guide future prevention interventions.

PMID- 10076488
TI  - A deviation bar chart for detecting dengue outbreaks in Puerto Rico.
AB  - OBJECTIVES: A Centers for Disease Control and Prevention deviation bar chart
      (Statistical Software for Public Health Surveillance) and laboratory-based
      surveillance data were evaluated for their utility in detecting dengue outbreaks
      in Puerto Rico. METHODS: A significant increase in dengue incidence was defined
      as an excess of suspected cases of more than 2 SDs beyond the mean for all 4-week
      periods from April through June (the period of lowest seasonal incidence), 1989
      through 1993. An outbreak was defined as a cumulative annual rate of reported
      dengue greater than 3 per 1000 population. RESULTS: Retrospective application of
      the system to 1994 data showed agreement with previous analyses. In 1995 and
      1996, 36.4% and 27.3%, respectively, of municipalities with a significant
      increase in reports for 2 or more consecutive weeks before the first week of
      September had an outbreak, compared with 9.0% (in 1995, P = .042) and 6.0% (in
      1996, P = .054) of towns without a significant increase. The system showed
      sensitivity near 40%, specificity near 89%, and accuracy in classifying
      municipalities near 84%. CONCLUSIONS: This method provides a statistically based,
      visually striking, specific, and timely signal for dengue control efforts.

PMID- 10076489
TI  - The new old epidemic of coronary heart disease.
AB  - OBJECTIVES: This study quantified the consequences for prevalence of increased
      survival of coronary heart disease (CHD) in the Netherlands from 1980 to 1993.
      METHODS: A multistage life table fitted observed mortality and registration rates
      from the nationwide hospital register. The outcome was prevalence by age, sex,
      period, and disease state. RESULTS: The prevalence of CHD from 1980 to 1993 was
      4.4% (men, aged 25 to 84 years) and 1.4% (women, aged 25 to 84 years). Between
      1980-1983 and 1990-1993, the incidence changed little, but age-adjusted
      prevalence increased by 19% (men) and 59% (women). CONCLUSIONS: Sharply
      decreasing mortality but near-constant attack rates of CHD caused distinct
      increases in prevalence, particularly among the elderly.

PMID- 10076490
TI  - Relationship of lipoprotein(a) levels to physical activity and family history of
      coronary heart disease.
AB  - OBJECTIVES: This study evaluated the association of physical activity with serum
      lipoprotein(a) [La(a)] levels in individuals according to whether they had a
      family history of coronary heart disease (CHD). METHODS: Lp(a) levels in 332
      healthy Spanish men aged 20 to 60 years were measured. Physical activity and
      family history of CHD were assessed. RESULTS: For men with a family history of
      CHD, the odds ratio for Lp(a) levels above the median value was 0.13 (95%
      confidence interval = 0.03, 0.50) in very active men (energy expended in physical
      activity > 300 kcal/day) compared with active men (energy expended in physical
      activity < 300 kcal/day). CONCLUSIONS: Regular daily physical activity in
      individuals with a family history of CHD could be useful for controlling Lp(a)
      levels.

PMID- 10076491
TI  - Morbidity and mortality attributable to alcohol, tobacco, and illicit drug use in
      Canada.
AB  - OBJECTIVES: This study estimated morbidity and mortality attributable to
      substance abuse in Canada. METHODS: Pooled estimates of relative risk were used
      to calculate etiologic fractions by age, gender, and province for 91 causes of
      disease or death attributable to alcohol, tobacco, or illicit drugs. RESULTS:
      There were 33,498 deaths and 208,095 hospitalizations attributed to tobacco, 6701
      deaths and 86,076 hospitalizations due to alcohol, and 732 deaths and 7095
      hospitalizations due to illicit drugs in 1992. CONCLUSIONS: Substance abuse
      exacts a considerable toll on Canadian society in terms of morbidity and
      mortality, accounting for 21% of deaths, 23% of years of potential life lost, and
      8% of hospitalizations.

PMID- 10076492
TI  - Body mass index, weight change, and incidence of self-reported physician
      diagnosed arthritis among women.
AB  - OBJECTIVES: This study examined the relationship between body mass index (BMI),
      weight change, and arthritis in women. METHODS: Data were taken from the 1982
      1984 National Health and Nutrition Examination Survey Epidemiologic Follow-Up
      Study of 3617 women, aged 25 to 74 years. RESULTS: Women with a BMI greater than
      32 at initial interview were at significantly higher risk of developing arthritis
      than women with a BMI of 19 to 21.9. Compared with stable-weight women with a BMI
      of less than 25, women who were obese at initial interview (BMI > 29) and who
      subsequently maintained their weight or gained more than 10% of their body weight
      were at significantly higher risk of developing arthritis. CONCLUSIONS: Attaining
      and maintaining a healthy weight may reduce the risk of developing arthritis.

PMID- 10076493
TI  - Trends in body weight among American Indians: findings from a telephone survey,
      1985 through 1996.
AB  - OBJECTIVES: This study compared trends in body mass index for American Indian men
      and women across selected regions of the United States. METHODS: Self-reported
      data were collected from the Behavioral Risk Factor Surveillance System. RESULTS:
      Among women in the Dakotas, New Mexico and Arizona, and Washington and Oregon,
      average adjusted body mass index increased significantly by 0.1 to 0.2 units per
      year. Among men in Alaska and the Dakotas, average adjusted body mass index also
      increased significantly by 0.1 to 0.2 units each year. CONCLUSIONS: Because of
      rapid increases in average body mass index, some American Indian populations
      could be burdened by an increased incidence of chronic disease.

PMID- 10076494
TI  - Skirting the issue: women and international health in historical perspective.
AB  - Over the last decades women have become central to international health efforts,
      but most international health agencies continue to focus narrowly on the maternal
      and reproductive aspects of women's health. This article explores the origins of
      this paradigm as demonstrated in the emergence of women's health in the
      Rockefeller Foundation's public health programs in Mexico in the 1920s and 1930s.
      These efforts bore a significant reproductive imprint; women dispensed and
      received services oriented to maternal and childbearing roles. Women's health and
      social advocacy movements in Mexico and the United States partially shaped this
      interest. Even more important, the emphasis on women in the Rockefeller programs
      proved an expedient approach to the Foundation's underlying goals: promoting
      bacteriologically based public health to the government, medical personnel,
      business interests, and peasants; helping legitimize the Mexican state; and
      transforming Mexico into a good political and commercial neighbor. The article
      concludes by showing the limits to the maternal and reproductive health model
      currently advocated by most donor agencies, which continue to skirt--or sidestep-
      major concerns that are integral to the health of women.

PMID- 10076495
TI  - The relation of the milk supply to infant mortality. 1906.

PMID- 10076496
TI  - Vaccinating high school students against hepatitis B: a school/STD clinic
      collaboration.

PMID- 10076497
TI  - Teaching kids about rabies.

PMID- 10076498
TI  - Socioeconomic status and cardiovascular response.

PMID- 10076499
TI  - On contraception and abortion in Armenia.

PMID- 10076500
TI  - Private health insurance in Ireland.

PMID- 10076501
TI  - Air pollution: prevention and long-term perspectives.

PMID- 10076502
TI  - Occasional smoking in a study of premenopausal women.

PMID- 10076503
TI  - Household firearms.

PMID- 10076504
TI  - Policy statements adopted by the Governing Council of the American Public Health
      Association, November 18, 1998.

PMID- 10076505
TI  - Identification of a novel bovine serum protein which is involved in human T-cell
      leukemia virus type I (HTLV-I)-induced syncytium formation.
AB  - By immunizing rats with cocultured HTLV-I-positive ILT8M2 and HTLV-I-negative
      MOLT-4-cells, we isolated a monoclonal antibody (mAb), designated as mAb R21,
      which enhances the syncytium formation induced by coculturing ILT8M2 cells with
      MOLT-4 cells. The antigen recognized by mAb R21 was found on the surface of all T
      cell, fibroblastoid, and epithelial cells lines, and a part of B-cell and
      myelomonocytoid cell lines. MAb R21 reacted with an approximately 17-kDa protein
      from ILT8M2 and MOLT-4 cell lysates in both nonreducing and reducing conditions
      by immunoblotting. Immunoprecipitation experiments using surface-labeled cells
      revealed that a 17-kDa protein is present on the surface of both ILT8M2 and MOLT
      4 cells. Since the enhancing activity by mAb R21 of syncytium formation was
      observed only in the presence of a factor contained in fetal calf serum (FCS)
      which seems to bind to mAb R21, we purified this serum factor from FCS using a
      mAb R21-coupled Sepharose 4B column. The purified protein, designated as R21
      protein, was revealed to be O-glycosylated but not N-glycosylated protein of
      approximately 17 kDa. The partial amino acid sequence of this protein indicates
      that R21 protein is a novel bovine serum protein which has approximately 90%
      amino acid homology with bovine platelet factor 4, a member of CXC chemokine
      family. These results indicate that the R21 protein on the surface of cells
      and/or in FCS may play an important role in the process of HTLV-I-induced
      syncytium formation by as yet unknown mechanism.

PMID- 10076506
TI  - Cloning of a long HIV-1 readthrough transcript and detection of an increased
      level of early growth response protein-1 (Egr-1) mRNA in chronically infected
      U937 cells.
AB  - To identify the pathways involved in HIV-1 modification of cellular gene
      expression, chronically infected U937 cells were screened by mRNA differential
      display. A chimeric transcript consisting of the 3' end of the LTR of a HIV-1
      provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long
      readthrough transcription might be one of the mechanisms by which gene expression
      could be modified in individual infected cells. Such a phenomenon may also be the
      first step towards the potential transduction of cellular sequences. Furthermore,
      the mRNA encoding for the transcription factor Egr-1 was detected as an over
      represented transcript in infected cells. Northern blot analysis confirmed the
      increase of Egr-1 mRNA content in both HIV-1 infected promonocytic U937 cells and
      T cell lines such as Jurkat and CEM. Interestingly a similar increase of Egr-1
      mRNA has previously been reported to occur in HTLV-1 and HTLV-2 infected T cell
      lines. Despite the consistent increase in the level of Egr-1 mRNA, the amount of
      the encoded protein did not appear to be modified in HIV-1 infected cells,
      suggesting an increased turn over of the protein in chronically infected cells.

PMID- 10076507
TI  - Active HIV-1 redistribution and replication in the brain with HIV encephalitis.
AB  - The central nervous system (CNS) is of particular importance in human
      immunodeficiency virus type 1 (HIV-1) infection. First, the CNS may be difficult
      to access for anti-retroviral treatment and may become a sanctuary for residual
      viruses. Second, HIV-1 infection may lead to AIDS dementia complex (ADC)
      culminating in HIV-1 encephalitis. In order to examine the pattern of drug
      resistance and the role of encephalitis in enhancing viral redistribution to the
      CNS, we compared pol gene quasispecies of the spleen and brain in two patients
      with and two patients without HIV-1 encephalitis, who had been treated with
      zidovudine (AZT). Although a variable degree of AZT resistance was noted in both
      the spleen and brain of all patients, phylogenetic analysis indicated that
      quasispecies developed rather independently in the systemic circulation (spleen)
      and CNS (brain) of patients without HIV-1 encephalitis, while similar pol gene
      sequences were obtained from the two compartments of patients with HIV-1
      encephalitis. env gene V3 region of patients with HIV-1 encephalitis showed
      distinct quasispecies in the spleen and brain. Our results suggest that HIV-1
      redistribution to CNS is more active in cases with encephalitis and that HIV-1
      distributed late to CNS grow actively under certain selective pressure exerted on
      the V3 region of the env gene.

PMID- 10076508
TI  - Re-isolation of Marek's disease virus from T cell subsets of vaccinated and non
      vaccinated chickens.
AB  - To know the effect of Marek's disease (MD) vaccines, we analyzed the distribution
      of MD virus (MDV) among T cell subsets from chickens vaccinated or non-vaccinated
      with MD vaccine and subsequently challenged with a virulent MDV. The challenged
      MDV was reisolated preferentially from CD4+ T cells, and the average titers of
      challenged MDV rescued were significantly lower in vaccinated chickens compared
      to that of non-vaccinated chickens. In addition, it was also shown that different
      serotypes of MDV, CVI988 and SB-1, have remarkable difference in recovery rates
      of viruses from CD4+ and CD8+ T cells, though both CVI988 and SB-1 can reduce the
      infection rates of virulent MDV to splenocytes.

PMID- 10076509
TI  - Pathotyping isolates of Newcastle disease virus using antipeptide antibodies to
      pathotype-specific regions of their fusion and hemagglutinin-neuraminidase
      proteins.
AB  - Antipeptide antibodies have been evaluated for their abilities to predict the
      characteristics of the cleavage motifs of the fusion protein precursors (F0) of
      25 isolates of Newcastle disease virus (NDV) with a range of virulences, grouped
      into 12 sets according to their monoclonal antibody reactivities. A Western blot
      format was used to show that antisera to synthetic peptides representing
      sequences at the C-termini of the F2-polypeptides of defined pathotypes of NDV
      usually distinguish between pathotypes on the basis of their Fo cleavage
      sequences. However, exceptions were found with three groups of virulent isolates.
      Protein sequencing and mass spectral analysis of the F2-polypeptide of isolate
      Texas GB from one of these groups, identified an anomalous cleavage/activation
      process which removed the amino acids required for recognition by the antisera.
      This probably also explained the lack of reactivity of the Roakin isolate and low
      reactivity of the Komarov isolate from this group. The other exceptions involved
      isolates in groups with cleavage region variations from the usual motif of
      virulent isolates or isolates with undefined cleavage motifs. Antipeptide
      antisera were also raised to sections of the 45 residue C-terminal extension the
      hemagglutinin-neuraminidase precursor (HN0) encoded by the genes of some
      avirulent isolates. Western blot analysis showed that positive reactions with
      antibodies to peptides based on sequences between residues 577 and 613 of the HN0
      was evidence for the presence of an avirulent isolate but did not exclude the
      presence of other pathotypes. Antisera designed to target residues 569-577
      detected HN0 extensions of 6 residues on isolates known to encode such
      extensions. These antisera also enabled differentiation of isolates with HN0
      extensions of 6 residues from those with no extension, however, it was not
      possible to determine the virulence of isolates based on reaction with these
      antisera.

PMID- 10076510
TI  - Insertion of sequences into the 3' untranslated region of a replication-competent
      spleen necrosis virus vector disrupts env gene expression.
AB  - The genomes of all replication-competent retroviruses contain cis-acting elements
      that regulate gene expression. However, the identities of many of these elements
      remain to be characterized. Inserting sequences into the 3' untranslated region
      of a replication-competent spleen necrosis virus (SNV) vector disrupted its
      ability to replicate. Inserts varying in sequences and sizes (0.4-kb to 1.6-kb)
      all resulted in this defect. Genetic compensation experiments and immunostaining
      revealed that env gene expression was deficient. Northern analysis indicated the
      presence of spliced viral mRNA of the correct size although at a reduced level
      compared to a wildtype vector. It is likely that the block in env expression
      occurs at a post-transcriptional step. These results suggest that the function of
      a cis-acting element distinct from the constitutive transport element is
      disrupted by the inserted sequences into the 3' untranslated region of SNV.

PMID- 10076511
TI  - Banana bunchy top virus DNA-2 to 6 are monocistronic.
AB  - Banana bunchy top virus (BBTV) DNA-3 to 6 have each previously been shown to
      contain one large open reading frame in the virion sense, whereas no large ORF
      had been identified in BBTV DNA-2. RNAs transcribed from the BBTV genome were
      mapped using northern hybridisation and 3' RACE. One mRNA was transcribed from
      each of BBTV DNA-2 to 6 and four of these mRNAs mapped to the ORFs previously
      identified in BBTV DNA-3 to 6. The mRNA of BBTV DNA-2 was transcribed from a
      virion sense ORF probably using a TATA box sequence different to that in BBTV DNA
      1, and DNA-3 to 6. This ORF encoded a 10 kDa protein of unknown function. The 3'
      untranslated region of the five mRNAs varied from 25 nucleotides (BBTV DNA-6) to
      167 nucleotides (BBTV DNA-4) and each contained putative polyadenylation signals
      with associated GT rich sequence together with a possible termination signal
      (C/T/A)TGTAA conserved in all five mRNAs.

PMID- 10076512
TI  - Respiratory syncytial virus G glycoprotein expressed using the Semliki Forest
      virus replicon is biologically active.
AB  - The respiratory syncytial virus (RSV) G glycoprotein mediates attachment of RSV
      to cells via an unknown receptor. To study G glycoprotein function we have cloned
      two variants of the RSV G gene into a Semliki Forest virus (SFV) expression
      vector, a full length (rG) and soluble (srG) G glycoprotein variant. By
      immunofluorescence microscopy, rG was found to be predominantly membrane
      associated, while srG was mostly cytoplasmic. The rG (80-85 kDa) and srG (75-80
      kDa) constructs produced heavily glycosylated proteins, however they were
      slightly smaller than the G glycoprotein expressed in RSV infected HEp-2 cells
      (85-90 kDa). The biological activity of purified srG was tested by its ability to
      bind to RSV permissive cells. Purified srG bound to HEp-2 cells and the amount
      bound increased linearly with the quantity added. Binding was not saturable with
      the small quantities of protein available. Binding of srG to HEp-2 cells was
      inhibited (67-68%) by MAb 30 and neutralising anti-G MAb 29. Nonpermissive SF9
      insect cells bound 20-50 times less srG than HEp-2 cells. SFV expressed
      recombinant RSV G glycoprotein should be useful for studying interactions between
      the RSV G glycoprotein and cells.

PMID- 10076513
TI  - T cell responses to the structural polypeptides of porcine reproductive and
      respiratory syndrome virus.
AB  - The identification of antigens recognized by T cell responses has become
      fundamental for developing effective immunizations against viral infections.
      Lymphocyte proliferation and delayed-type hypersensitivity responses to porcine
      reproductive and respiratory syndrome virus (PRRSV) infection have been
      demonstrated. However, the polypeptide specificity of T cell responses to PRRSV
      is unknown. To identify the PRRSV polypeptides recognized by porcine lymphocytes
      two approaches were employed. First polypeptides of purified virions were
      separated by SDS-PAGE and particle suspensions obtained from nitrocellulose blots
      were used as antigens. Second, the polypeptides encoded by ORFs 2, 4, 5, 6, and 7
      of the strain VR-2332 were expressed as fusion proteins with a histidine tag in
      mammalian cells, using vaccinia virus as expression system. Significant antigen
      specific proliferation responses to the matrix and envelope proteins from
      purified virions were obtained. This finding was supported by specific and dose
      dependent proliferation responses to the recombinant polypeptides encoded by
      ORF2, 5 and 6 detected in virus-infected but not in control pigs. These results
      demonstrate that T-cell responses can be detected to individual PRRSV
      polypeptides. The greater response to the product of ORF6 than to the other PRRSV
      polypeptides indicates that the viral matrix polypeptide may have a major role in
      cellular immunity.

PMID- 10076514
TI  - Sequence analysis of rabbit haemorrhagic disease virus (RHDV) in Australia:
      alterations after its release.
AB  - Liver samples from rabbits killed by RHDV, collected from five States in
      Australia in 1996 and 1997 were analysed by RT-PCR. A 398 bp fragment of the
      capsid protein (VP60) gene was amplified by PCR and directly sequenced. The
      alignment of the nucleotide and amino acid sequences and their comparison with
      the original strain of the virus released in Australia indicated genetic changes
      after two years have been small with 98.2% to 100% identity. The constructed
      phylogenetic tree suggests slight differences in nucleotide substitutions in
      various States but there is no clear evidence of clustering of sequences
      according to their geographic origin. In practical terms, sequencing of viral RNA
      provides a means of testing the efficacy of further releases and subsequent
      spread of the virus if such a strategy is employed as a means of enhancing RHD as
      a biological control of the wild rabbit in Australia.

PMID- 10076515
TI  - A novel amino acid substitution at the receptor-binding site on the hemagglutinin
      of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy
      during the 1997-1998 season in Tokyo.
AB  - We analyzed the hemagglutinin (HA) genes of influenza A viruses consisting of 6
      strains isolated from cerebrospinal fluids of patients with encephalopathy and 3
      isolates from throat washes of patients without central nervous system symptoms
      during the 1997-1998 season in Tokyo. Aligned 9 amino acid sequences showed 7
      common substitutions compared with A/Wuhan/359/95 (vaccine strain used in the
      season in Japan), which were allocated to three different antigenic sites on the
      H3 HA molecule. It is noted that a novel substitution at the receptor-binding
      site (Tyr-137 to Phe) was found exclusively in the isolates from the patients
      with encephalopathy.

PMID- 10076516
TI  - Expression of latent and replicative-infection genes of Epstein-Barr virus in
      macrophage.
AB  - Unlike other herpesviruses, Epstein-Barr virus (EBV) has not yet been shown to
      infect macrophages. Six macrophage cultures were isolated from normal and
      affected samples. Nested polymerase chain reaction revealed the existence of the
      EBV genome in all these macrophages. EBV latent genes expression in all cultures
      were detected by mRNA in situ hybridization and immunofluorescence staining. Some
      cultures also expressed EBV replicative-infection proteins, while in other
      cultures induction of these proteins was demonstrated. These findings are the
      first to show expression of several latent and replicative-infection genes of EBV
      in macrophages, indicating that EBV proliferates in macrophages.

PMID- 10076517
TI  - Experimental inoculation of adult dairy cows with bovine coronavirus and
      detection of coronavirus in feces by RT-PCR.
AB  - A reverse transcriptase PCR (RT-PCR) targeting a 407 bp fragment of the
      nucleocapsid gene of bovine coronavirus (BCV) was developed for detection of BCV
      RNA in feces of experimentally inoculated cattle. The sensitivity and specificity
      of the RT-PCR were confirmed using tissue culture-adapted BCV strains and feces
      of 2 calves inoculated with BCV. Ten nonpregnant, BCV seropositive, adult dairy
      cows were inoculated with winter dysentery (WD) (n = 8) or calf diarrhea (CD) (n
      = 2) strains of BCV intranasally and orally (n = 2) or through a surgically
      placed duodenal catheter (n = 8) with and without dexamethasone treatment or
      feeding ice water. The 6 cows inoculated with BCV intranasally and through a
      duodenal catheter (2 of 2 cows given CD BCV and 4 of 6 cows given WD BCV)
      developed mild diarrhea, and BCV was detected in diarrheal feces by RT-PCR, ELISA
      or immune electron microscopy. These results suggest that CD and WD strains of
      BCV can cause diarrhea in adult cows in conjunction with host or environmental
      factors and that RT-PCR might be useful to diagnose BCV infections in calves and
      adult cows.

PMID- 10076518
TI  - Detection methods of possible prion contaminants in collagen and gelatin.
AB  - We describe methods for the preparation of collagen and gelatin samples to detect
      possible prion contaminants using Western blotting of a major component of
      prions, PrPSc. A commercially available collagen solution containing 2% athero
      collagen was spiked with rodent adapted scrapie prion and used as the prion
      contaminating collagen. The methods developed center on the enzymatic reduction
      of the collagen solution viscosity with protease treatments and on the
      concentration of the prion from the protease-digests with polyethylene glycol
      #6000 and NaCl. Recovery of the spiked prion as a partially protease-resistant
      core fragment of PrPSc fluctuated from 30% to 46% of the input amount.

PMID- 10076519
TI  - Molecular characterization of the RNA3 of asparagus virus 2.
AB  - Asparagus virus 2 (AV 2) has been detected in all major asparagus growing areas
      around the world and it has been suggested that, in association with other
      pathogens, it might be an important factor for the condition called asparagus
      decline. Although AV 2 was first reported in the 70's, only few of its
      biochemical characteristics have been actually studied. Some properties of an AV
      2 isolate from Guanajuato, Mexico were characterized and its RNA3 cloned and
      sequenced. Electrophoretic analysis of AV 2 RNA showed 3 genomic RNAs (RNA1. 3.0;
      RNA2 2.7; and RNA3 2.3 kb) and a fourth, subgenomic, RNA4 of 1.1 kb. In vitro
      translation data confirmed that coat protein is produced by translation of the
      subgenomic RNA4, as reported for other bromoviruses. Sequence analysis of AV 2
      RNA3 showed two open reading frames identified by sequence comparisons and
      immunological assays as coding the movement and coat proteins (MP and CP,
      respectively). AV 2 CP showed a high percentage of identity with the CPs from
      other members of the subgroup II of the ilarvirus genus. The percentage of
      identity with other ilarviruses decreased dramatically and in some cases was
      lower than the values obtained with members of different genera.

PMID- 10076520
TI  - Association between the sigma C protein of avian reovirus and virus-induced
      fusion of cells.
AB  - Monoclonal antibodies (MAbs) against a 39 kDa (sigma C) protein of the avian
      reovirus RAM-1 strain inhibited virus-induced fusion of cells and the protein was
      expressed on the surface of infected cells. The fusion-inhibiting activity of the
      three MAbs reacting with the sigma C protein suggest two putative epitopes were
      involved: one epitope recognised by antibody 6H1 and involved in fusion of both
      Vero and CK cells and a second epitope recognised by antibody 1G1 involved in
      fusion of Vero cells but not CK cells. The activity of the MAb 6E2 was
      intermediate, suggesting it may have been located in an intermediate position
      between the two putative epitopes and inhibited fusion by steric hindrance.

PMID- 10076522
TI  - Classification of reverse transcribing elements: a discussion document.

PMID- 10076521
TI  - Complete nucleotide sequence and genomic organization of a primate calicivirus,
      Pan-1.
AB  - The primate calicivirus, Pan-1, was originally isolated from several primate
      species. It displayed typical calicivirus morphology by electron microscopy. We
      determined the genomic sequence of Pan-1 by cDNA cloning and direct RNA
      sequencing. Pan-1 shares a similar genomic organization and a high degree of
      sequence identity with feline caliciviruses. The Pan-1 genome contains 8,304
      nucleotides, plus a poly-A tail, and is longer than any other calicivirus strains
      with a completely known sequence. The extra sequences of Pan-1 include a unique
      424-nucleotide sequence at the 5' end of ORF1, additional amino acids at the N
      terminus of the capsid, and a longer 3' UTR.

PMID- 10076523
TI  - Ras, superoxide and signal transduction.
AB  - The superoxide anion has been associated with the bactericidal activity of
      phagocytes. Produced by an enzymatic complex, NADPH oxidase, bactericidal
      superoxide is released within phagolysosomes where bacteria are being degraded.
      The activity of NADPH oxidase is regulated by Rac, a small GTP binding protein of
      the Ras family. Recent evidence indicates that, in addition to its bactericidal
      activity, superoxide seems to function as a signal-transduction messenger,
      mediating the downstream effects of Ras and Rac in nonphagocytic cells. As such,
      superoxide contributes to the unchecked proliferation of Ras-transformed cells.
      In the nitric oxide (NO) system, low concentrations of NO transduce signals
      within vessels and neurons, while high concentrations of NO can produce damage to
      cells and microorganisms. By analogy, superoxide and probably other oxidants
      serve as messengers at low concentrations, while larger amounts are required for
      inducing damage. The activity of oxidants as messengers opens new avenues for
      pharmacological intervention against Ras-mediated pathways in mammalian cells.

PMID- 10076524
TI  - Modes of interactions between signaling pathways.
AB  - The study of signaling pathways has begun to uncover the mechanism by which cells
      respond and adapt to extracellular stimuli. It has become increasingly clear that
      the signaling pathways interact with one another to form a complex network
      through which regulation occurs. Here, we focus on three mechanisms by which
      signaling pathways interact and the physiological consequences of these
      interactions. Coincident signaling in long-term depression of synaptic responses
      in the cerebellum, protein kinase A gating of Ras to mitogen-activated protein
      kinase signal flow in proliferative responses, and a modified gating mechanism by
      phosducin resulting in feedback regulation of signal flow from rhodopsin to the
      cGMP phosphodiesterase in retinal light adaptation are analyzed as examples of
      different types of interactions between signaling pathways. These interactions
      allow the cell to spatially and temporally integrate complex information and
      respond in an appropriate and defined manner.

PMID- 10076525
TI  - Effects of perturbations of pools of deoxyribonucleoside triphosphates on
      expression of ribonucleotide reductase, a G1/S transition state enzyme, in p53
      mutated cells.
AB  - Effects of drug treatment with antimetabolites on a human colon cancer cell line,
      SW480, were studied. Cells were treated with 10 microM of 5-fluorouracil (5FU),
      an inhibitor of pyrimidine synthesis, or 1000 microM of hydroxyurea (HU), an
      inhibitor of both purine and pyrimidine syntheses, or the combination.
      Recombinant alpha-2a-interferon (IFN), 500 U/mL, also was employed, as this
      augments the effects of both antimetabolites in vitro and in vivo. The
      predominant effect of this combination was to block cells in early S phase as
      measured by 5-bromo-2'-deoxyuridine (BrdUrd) incorporation. By 24 hr, 86% of the
      cells had accumulated in S phase, but failed to progress to G2/M. This was
      accompanied by an early, rapid decline in all four deoxyribonucleoside
      triphosphates (dNTPs) by 38-86% at 4-24 hr. Despite these effects, expression of
      the G1/S transition state enzyme, ribonucleotide reductase (RR), increased at 24
      hr as measured by a 3 to 5-fold increase in mRNA levels for the M2 subunit, in
      the absence of a measurable effect on protein levels. The rise in levels of RR
      mRNA and the continued progression of cells into S phase were associated with a
      synergistic inhibition of cell cycle proliferation resulting from treatment with
      the three-drug combination. This suggests that in the presence of antimetabolite
      induced depletion of dNTPs, SW480 cells, which lack a normal p53 gene, will
      proceed into S phase, and that this is associated with a rise in expression of
      the G1/S transition state enzyme, RR. Cells arrested in S phase by a p53
      independent mechanism will undergo a synergistic enhancement of cell death.

PMID- 10076526
TI  - Effects of methylglyoxal on rat pancreatic beta-cells.
AB  - The addition of the alpha-ketoaldehyde methylglyoxal (0.5 or 1 mmol/L) to single
      isolated rat pancreatic beta-cells caused a rapid, marked depolarization
      resulting in electrical activity. This effect of methylglyoxal on beta-cell was
      reversible upon removal of the alpha-ketoaldehyde, and could be inhibited by the
      anion channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS)
      and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Methylglyoxal also
      resulted in elevated cytosolic [Ca2+] and an intracellular acidification in
      intact rat islets. In perifused islets, methylglyoxal provoked a modest,
      transient stimulation of secretion but inhibited glucose-induced insulin release.
      Incubation of islets with methylglyoxal resulted in the formation of large
      quantities of D-lactate, indicating metabolism of the alpha-ketoaldehyde via the
      glyoxalase pathway. The effects of methylglyoxal on beta-cell membrane potential,
      cytosolic [Ca2+] and intracellular pH were also observed in response to
      phenylglyoxal which is also effectively metabolized via the glyoxalase pathway.
      However, t-butylglyoxal which is poorly metabolized via the glyoxalase pathway,
      caused neither depolarization of the membrane potential nor intracellular
      acidification, but did inhibit glucose-induced insulin release. These findings
      suggests that the depolarization and acidification evoked by methyl- and
      phenylglyoxal are dependent upon their metabolism via the glyoxalase pathway. The
      possible mechanisms coupling alpha-ketoaldehyde metabolism via the glyoxalase
      pathway with membrane depolarization are discussed.

PMID- 10076527
TI  - Structure-related inhibition of human hepatic caffeine N3-demethylation by
      naturally occurring flavonoids.
AB  - The effects of flavonoids on caffeine N3-demethylation, a marker activity of
      CYP1A2, in human liver microsomes were investigated to elucidate the inhibition
      mechanism and the structure-activity relationship. Caffeine N3-demethylase
      activity was inhibited by the presence of various flavonoids, whose structures
      seem to be closely related to the degree of inhibition. Among twenty-one
      compounds tested, the most active was chrysin with an IC50 value of 0.2 microM.
      Others had IC50 values ranging from 1 to more than 500 microM. Kinetic analysis
      revealed that the mechanism of inhibition varied among the flavonoids. The
      inhibitory effect was postulated to be governed by factors such as the number of
      hydroxyl groups and glycosylation of these free hydroxyl groups. An increase in
      the number of free hydroxyl groups reduced the inhibitory effect on P450
      activity. Analysis of the quantitative structure-activity relationship (QSAR)
      showed that the volume to surface area ratio was the most effective factor on the
      inhibition of caffeine N3-demethylation, and the electron densities on the C3 and
      C4' atoms exercised significant influence on the inhibitory effect. The
      calculated inhibitory effect of flavonoids on CYP1A2 activity was highly
      correlated with the antimutagenicity of flavonoids in 2-amino-3,4
      dimethylimidazo[4,5-flquinoline (MelQ)-induced umu response.

PMID- 10076528
TI  - Tobacco-specific carcinogenic nitrosamines. Ligands for nicotinic acetylcholine
      receptors in human lung cancer cells.
AB  - Lung cancer demonstrates a strong etiologic association with smoking. Of the two
      most common histologic lung cancer types, small cell carcinoma (SCLC) is found
      almost exclusively in smokers, whereas peripheral adenocarcinoma (PAC) also
      develops in a significant number of nonsmokers. N'-Nitrosonornicotine (NNN) and
      4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), nicotine-derived
      nitrosamines, are potent lung carcinogens contained in tobacco products. Because
      of the structural similarity of NNN and NNK with nicotine, we hypothesized that
      these carcinogens are ligands for nicotinic acetylcholine receptors (nAChRs).
      Using cell lines derived from human small cell lung carcinoma and pulmonary
      adenocarcinoma with the site-selective ligands alpha-bungarotoxin (alpha-BTX) and
      epibatidine (EB) in receptor binding and cell proliferation assays, we found that
      SCLC expressed neuronal nicotinic receptors with high affinity to alpha-BTX,
      whereas PAC cells expressed nicotinic receptors with high affinity to EB. NNK
      bound with high affinity to alpha-BTX-sensitive nAChRs in SCLC cells, while NNN
      bound with high affinity to EB sensitive nAChRs in PAC cells. The affinity of
      each nitrosamine to these receptors was several orders of magnitude greater than
      that of nicotine. NNK stimulated the proliferation of SCLC cells via this
      mechanism. Our findings suggest that NNK may contribute to the genesis of SCLC in
      smokers via chronic stimulation of the alpha BTX-sensitive nAChR-subtype
      expressed in these cells. Both nitrosamines may also contribute to a host of
      nicotine-related diseases that are currently thought to be caused by the chronic
      interaction of nicotine with nAChRs expressed in a large spectrum of mammalian
      cells.

PMID- 10076529
TI  - Requirement of expression of P-glycoprotein on human natural killer leukemia
      cells for cell-mediated cytotoxicity.
AB  - The requirement of P-glycoprotein, a product of the multidrug resistance (MDR)1
      gene, for natural killer (NK) cell-mediated cytotoxicity was examined by using a
      human NK-like cell line, YTN, which is cytotoxic toward JY cells. YTN cells
      express P-glycoprotein, a judged by flow cytometry and polymerase chain reaction
      of reverse-transcribed mRNA. YTN cell-mediated cytotoxicity was inhibited by MDR
      reversing reagents as well as the F(ab')2 fragment of a monoclonal antibody
      against P-glycoprotein. Furthermore, antisense oligonucleotides for MDR1 mRNA
      inhibited expression of P-glycoprotein as well as YTN cell-mediated cytotoxicity.
      Thus, this study provides firm evidence that P-glycoprotein plays an essential
      role in cell-mediated cytotoxicity.

PMID- 10076530
TI  - A new structural class of proteasome inhibitors that prevent NF-kappa B
      activation.
AB  - The multicatalytic proteinase or proteasome is a highly conserved cellular
      structure that is responsible for the ATP-dependent proteolysis of many proteins
      involved in important regulatory cellular processes. We have identified a novel
      class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S
      proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to
      1 microM). In cell proliferation assays, these compounds inhibit growth with an
      IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member
      of this class of inhibitors was tested in other biological assays. CVT-634 (5
      methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented
      lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced
      activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal
      induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha
      that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit
      I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation
      of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced
      TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated
      with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF
      levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively)
      than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These
      studies suggest that specific inhibition of the chymotrypsin-like activity of the
      proteasome is sufficient to prevent signal-induced NF-kappa B activation and that
      the proteasome is a novel target for the identification of agents that may be
      useful in the treatment of diseases whose etiology is dependent upon the
      activation of NF-kappa B.

PMID- 10076531
TI  - Involvement of phenoxyl radical intermediates in lipid antioxidant action of
      myricetin in iron-treated rat hepatocyte culture.
AB  - Supplementation of rat hepatocyte cultures with the flavonoid myricetin (300
      microM) led to the formation of phenoxyl radical intermediates, as detected in
      intact cells by electron paramagnetic resonance (EPR) spectroscopy. These
      radicals corresponded to one-electron oxidation products of myricetin. The level
      of phenoxyl radicals was significantly reduced when myricetin-treated hepatocyte
      cultures were also supplemented with iron (Fe-NTA 100 microM). This suggested
      that iron could accelerate the oxidation flux of myricetin. Moreover, myricetin
      was found to be able to inhibit lipid peroxidation induced by iron in hepatocyte
      culture. Free malondialdehyde (MDA) levels and the amount of radicals derived
      from oxidized lipids were greatly reduced when myricetin was added to iron
      treated cultures. This showed that myricetin was a good inhibitor of lipid
      peroxidation in this model and that the intermediate generation of phenoxyl
      radicals might contribute to the antioxidant mechanism of myricetin.

PMID- 10076532
TI  - Strain differences in CYP3A-mediated C-8 hydroxylation (1,3,7-trimethyluric acid
      formation) of caffeine in Wistar and Dark Agouti rats. Rapid metabolism of
      caffeine in debrisoquine poor metabolizer model rats.
AB  - We observed significant strain differences [Dark Agouti (DA) > Wistar] in 1,3,7
      trimethyluric acid formation (C-8 hydroxylation) during caffeine metabolism,
      though not in N-demethylations, in adult male DA and Wistar rats. In contrast,
      adult female and immature male rats of both DA and Wistar strains did not show
      significant differences in activity levels of C-8 hydroxylation. Kinetic studies
      using liver microsomes revealed that adult male DA rats have a larger Vmax for C
      8 hydroxylation than do Wistar rats. Troleandomycin (TAO), known as a cytochrome
      P450 (CYP) 3A inhibitor, and an anti-rat CYP3A2 polyclonal antibody effectively
      reduced C-8 hydroxylation by rat liver microsomes in a concentration-dependent
      manner, suggesting that C-8 hydroxylation in rats is mediated largely by an
      isoform(s) of the CYP3A subfamily. Troleandomycin and the antibody did not
      inhibit the N-demethylations of caffeine by rat liver microsomes. Treatment of
      rats with CYP3A inducers caused a marked increase in C-8 hydroxylase activity.
      These results indicate that the rat CYP3A subfamily is capable of catalyzing C-8
      hydroxylation of caffeine as is the case for human CYP3A4. The results of western
      blotting analysis using anti CYP3A antiserum showed that the staining intensity
      of the protein band in DA rat liver microsomes was higher than that in Wistar rat
      liver microsomes. We concluded that marked sex-dependent strain differences in C
      8 hydroxylation of caffeine between Wistar and DA rats are due to the differences
      in the levels of expression of CYP3A in these strains of rats.

PMID- 10076533
TI  - Ca2+ mobilization in adult rat cardiomyocytes by angiotensin type 1 and 2
      receptors.
AB  - The role of angiotensin II (AngII) in the regulation of heart function under
      normal and pathological conditions has been well documented. Although two types
      of AngII receptors (AT1 and AT2 receptors) are found in equal proportions in the
      rat heart, most studies have focused primarily on AT1 receptor-coupled events. In
      this study, the contribution of both types of AngII receptors to cardiac function
      was evaluated by measuring intracellular calcium ([Ca2+]i) levels at ambient
      temperature in freshly isolated adult rat ventricular cardiomyocytes. Exposure of
      cardiomyocytes to AngII (0.01 to 10 microM) resulted in an immediate and
      sustained increase in [Ca2+]i in a concentration-dependent manner. The increase
      in [Ca2+]i in cardiomyocytes by AngII was blocked by either losartan or compound
      PD123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-
      4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid), non-peptide
      antagonists of the AT1 and AT2 receptors, respectively. The specificity of the
      action of these antagonists was verified by their inability to alter the basal
      levels of [Ca2+]i as well as KCl- or ATP-induced increases in [Ca2+]i. AngII was
      also observed to initiate spontaneous beating activity in cardiomyocytes, which
      was prevented by both losartan and compound PD123319 in a concentration-dependent
      manner (0.01 to 10 microM). These data indicate that the activation of both AT1
      and AT2 receptors may stimulate a signalling pathway that influences [Ca2+]i and
      spontaneous beating activity in cardiomyocytes.

PMID- 10076534
TI  - Prevention of tolerance to the organophosphorus anticholinesterase paraoxon with
      carboxylesterase inhibitors.
AB  - The contribution of carboxylesterase (CarbE) to the development of tolerance to
      the organophosphorus anticholinesterase (OP-ANTIChE) paraoxon (diethyl p
      nitrophenyl phosphate) was investigated in rats. Daily injections (20 days) of
      paraoxon (0.09 mg/kg) led to a cumulative dose that was 9.0-fold higher than the
      acute ED50 of 0.20 mg/kg, s.c. During this period, the rats did not demonstrate
      visible signs of cholinergic hyperactivity nor did they die, despite the
      persistence of critically reduced brain acetylcholinesterase (AChE) activity (20
      30% of control). In addition, none of these rats died following the
      administration of a dose of carbachol (3.1 mg/kg, i.p.) that was an LD90 in
      untreated rats. Daily treatment with the CarbE inhibitors CBDP [2-(o-cresyl)-4H
      1,3,2-benzodioxaphosphorin-2-oxide] (2 mg/kg, s.c.) or iso-OMPA
      (tetraisopropylpyrophosphoramide) (3 mg/kg, i.p.) followed by paraoxon (0.09
      mg/kg, s.c.) 60 min later prevented the development of tolerance to paraoxon,
      since signs of cholinergic hyperactivity were observed and rats died on day 4 of
      the combined treatment. In tolerant rats, one-time CBDP or iso-OMPA pretreatment
      increased toxicity to paraoxon, causing the death of all rats within 60 min. The
      increase in paraoxon toxicity was correlated with inhibition of a plasma CarbE,
      with high affinity toward alpha-naphthyl acetate (alpha-NA) and to the inhibitors
      CBDP, iso-OMPA, and paraoxon. Inhibition of a plasma CarbE with high affinity
      toward p-nitrophenyl acetate (p-NPA) and low affinity to the above inhibitors did
      not potentiate paraoxon toxicity significantly. Neither the liver CarbEs, which
      showed high affinity to iso-OMPA, nor the inhibition of butyrylcholinesterase
      (BuChE) by iso-OMPA in plasma and liver potentiated paraoxon toxicity. By
      eliminating plasma CarbE (alpha-NA) as potential binding sites for paraoxon with
      either CBDP or iso-OMPA, paraoxon can exert its toxicity to a greater extent at
      its specific target site, the functionally important AChE at cholinergic
      synapses. It is concluded that plasma CarbE (alpha-NA) provided a significant
      protection against paraoxon intoxication and that the inhibition of this enzyme
      prevented the tolerance development seen with repeated paraoxon treatments.

PMID- 10076535
TI  - Androgen antagonistic effect of estramustine phosphate (EMP) metabolites on wild
      type and mutated androgen receptor.
AB  - Estramustine phosphate is used frequently, alone or in combination with other
      antitumor agents, for the treatment of hormone-refractory prostate cancer.
      Estramustine phosphate is metabolically activated in vivo, and its metabolites,
      estramustine, estromustine, estrone, and beta-estradiol inhibit the assembly of
      microtubules [for review see: Kreis W, In: Concepts, Mechanisms, and New Targets
      for Chemotherapy (Ed. Muggia FM), pp. 163-184. Kluwer Academic Publishers,
      Boston, 1995]. We investigated, by displacement of [3H]methyltrienolone in the
      presence of 2.5 mM of triamcinolone acetonide, the binding of estramustine
      phosphate and its metabolites, estramustine, estromustine, estrone, and beta
      estradiol, as well as other antiandrogen agents including alpha-estradiol,
      bicalutamide, and hydroxyflutamide, to the mutated androgen receptor (m-AR) in
      LNCaP cells and to the wild-type androgen receptor in wild-type AR cDNA
      expression plasmid (w-pAR0) cDNA-transfected HeLa cells. Analogous to the
      antiandrogens, bicalutamide and hydroxyflutamide, binding of estramustine
      phosphate metabolites to the androgen receptor was observed. The EC50 values (in
      microM) were: estramustine phosphate, > 10; estramustine, 3.129 +/- 0.312;
      estromustine; 2.612 +/- 0.584; estrone, 0.800 +/- 0.090; alpha-estradiol, 1.051
      +/- 0.096; beta-estradiol, 0.523 +/- 0.028; bicalutamide, 4.920 +/- 0.361; and
      hydroxyflutamide, 0.254 +/- 0.012. The transactivation assay demonstrated that,
      analogous to bicalutamide, estramustine could not induce luciferase activity in
      either w-pAR0 or m-pARL transfected HeLa cells. In contrast, a strong induction
      of the reporter activity by dihydrotestosterone was observed. Down-regulation of
      prostate-specific antigen (PSA) expression, an AR-target gene, by estramustine
      and bicalutamide was accompanied by the blockade of the mutated androgen
      receptor. Exposure of LNCaP cells to estramustine for 24 hr caused
      transcriptional inhibition of PSA in a concentration-dependent manner. The levels
      of PSA mRNA decreased 56 and 90% when LNCaP cells were treated with 5 and 10
      microM of estramustine, respectively (IC50 = 10.97 +/- 1.68 microM). Binding of
      hydroxyflutamide to m-AR in LNCaP cells resulted in a concentration-dependent
      stimulation of PSA expression, suggesting that hydroxyflutamide acted as an
      agonist of the m-AR. Our data indicate that estramustine phosphate metabolites
      perform as androgen antagonists of AR, an additional mechanism involved in the
      therapeutic effect of estramustine phosphate in patients with prostate cancer.

PMID- 10076536
TI  - Negative regulation by dexamethasone of fluvastatin-inducible CYP2B expression in
      primary cultures of rat hepatocytes: role of CYP3A.
AB  - Fluvastatin (Fluva), a synthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase, induces CYP2B1/2 in rat liver and primary cultured rat hepatocytes.
      However, the overall profile of CYP induction, which includes induction of CYP4A,
      suggests that Fluva is not a typical "phenobarbital (PB)-like" inducer. Several
      treatments affecting diverse cell signaling pathways have been reported to modify
      PB-inducible CYP2B expression in primary cultured rat hepatocytes. We examined
      the effects of selected treatments on the ability of Fluva to induce CYP2B1/2
      mRNA. Only dexamethasone (Dex) produced effects on Fluva-inducible CYP2B1/2 mRNA
      expression that differed from those produced on PB-inducible CYP2B1/2 mRNA
      expression. Dex concentrations up to 10(-7) M of potentiated PB (10(-4) M)
      mediated CYP2B1/2 mRNA induction, while higher Dex concentrations produced a
      progressive reduction in PB-induced CYP2B1/2 mRNA levels. By contrast, Dex
      concentrations up to 10(-8) M had no effect on Fluva (3 x 10(-5) M)-induced
      CYP2B1/2 mRNA levels, while Dex concentrations of 10(-7) M and higher markedly
      suppressed Fluva-mediated CYP2B1/2 mRNA induction. The concentrations of several
      glucocorticoids that produced suppression of Fluva-induced CYP2B1/2 mRNA levels
      were the same concentrations that induced CYP3A mRNA. Treatment with pregnenolone
      16 alpha-carbonitrile also produced a concentration-dependent suppression of
      Fluva-induced CYP2B1/2 mRNA levels. Dex-mediated suppression of Fluva-induced
      CYP2B1/2 mRNA was concentration-dependently reversed when hepatocytes were
      cotreated with troleandomycin, a selective CYP3A inhibitor. The amounts of Fluva
      detected in culture medium and cells were reduced significantly when hepatocytes
      were incubated with Dex. However, Dex-mediated suppression of Fluva-induced
      CYP2B1/2 mRNA expression was not overcome when hepatocytes were incubated with
      Fluva concentrations greater than 3 x 10(-5) M, suggesting that mechanisms other
      than CYP3A-catalyzed metabolism may contribute to Dex-mediated suppression of
      Fluva-induced CYP2B1/2 expression.

PMID- 10076537
TI  - Metabolic activation of vinyl chloride by rat liver microsomes: low-dose kinetics
      and involvement of cytochrome P450 2E1.
AB  - The metabolism and pharmacokinetics of vinyl chloride (VC) have been extensively
      studied in rodents and humans, but the maximum velocity (Vmax) and Michaelis
      constant (K(m)) for the activation of VC by microsomal monooxygenases in vitro
      have not yet been determined. Using a new sensitive assay, the epoxidation of VC
      by rat liver microsomes (adult Sprague-Dawley) at concentrations from 1 ppm to
      10(6) ppm in the gas phase was measured. In the assay, the reactive VC
      metabolites chloroethylene oxide and 2-chloroacetaldehyde were trapped with
      excess cAMP, yielding, 1,N6-etheno-cAMP (epsilon cAMP) which was quantitated by
      HPLC fluorimetry. The trapping efficiency of electrophilic VC metabolites by cAMP
      was close to 10%. The specificity of the method was confirmed by purification of
      epsilon cAMP on an immunogel. The VC concentration in the gas phase was measured
      by GC/flame ionization detection, while in the aqueous phase it was calculated
      from the partition coefficient between air and the microsomal suspension.
      Activation of VC by rat liver microsomes followed Michaelis-Menten kinetics with
      K(m) = 7.42 +/- 0.37 (+/- SD) microM and Vmax = 4674 +/- 46 pmol.mg protein-1.min
      1. Inhibitor studies and immunoinhibition assays showed that VC was activated by
      cytochrome P450 (CYP) 2E1 down to 1 ppm in the air phase. Based on the metabolic
      parameters determined, the uptake of VC by rats in vivo can be accurately
      predicted.

PMID- 10076538
TI  - Rat pancreatic islet and RINm5F cell responses to epiandrosterone,
      dehydroepiandrosterone and interleukin-1 beta.
AB  - Epiandrosterone (EA), dehydroepiandrosterone (DHEA), and their sulfate (-S) and
      acetate (-A) conjugates were investigated for effects on isolated pancreatic
      islets and RINm5F insulinoma cells. Interleukin-1 beta (IL-1 beta) inhibited
      glucose-stimulated insulin release in cultured islets, but the presence of EA, EA
      A, and to a lesser extent EA-S, preserved the secretory response. IL-1 beta also
      increased islet nitrite production, which was antagonized by EA and EA-A, but not
      by EA-S. EA, EA-A, DHEA, and DHEA-A, but not EA-S and DHEA-S inhibited glucose
      stimulated insulin release from islets. This response may be related to the
      inhibition of glucose transport by EA, EA-A, DHEA, DHEA-A, and DHEA-S, as
      observed in RINm5F cells. EA, EA-A, DHEA, and DHEA-A also inhibited glucose
      metabolism in RINm5F cells, whereas EA-S and DHEA-S had no effect. EA, EA-A,
      DHEA, and DHEA-A, but not the sulfate conjugates, also inhibited RINm5F cell IL-1
      beta-induced nitric oxide synthase (iNOS) activity. IL-1 beta also increased
      cytosolic Cu/Zn-superoxide dismutase (SOD) and mitochondrial Mn-SOD in RINm5F
      cells. EA inhibited RINm5F cell Cu/Zn-SOD in the presence and absence of IL-1
      beta, whereas EA-S increased basal enzyme activity and did not affect the IL-1
      beta response. EA did not affect basal Mn-SOD activity and inhibited IL-1 beta
      stimulated activity, whereas EA-S was without effect. IL-1 beta had no effect on
      catalase activity in RINm5F cells, whereas EA, EA-A, and DHEA-A inhibited
      catalase activity. Thus, EA and DHEA and their acetate congeners protected the
      beta-cell from the inhibitory effects of IL-1 beta, and inhibited glucose
      transport and oxidation, and inducible nitricoxide synthase expression. EA and
      DHEA also had profound effects on Cu/Zn-SOD, which may alter the toxic effects of
      hydrogen peroxide generation in beta-cells.

PMID- 10076539
TI  - Sequence dependency of the internalization and distribution of phosphorothioate
      oligonucleotides in vascular smooth muscle cells.
AB  - Antisense studies imply the utilization of oligonucleotides (ODN) for sequence
      specific down-regulation of genes. This usually consists in assessing antisense
      sequences versus control sequences (mismatched, inverted, scrambled, randomized
      or any sequence unrelated to the relevant target). Even though the investigated
      biological effect (knockdown of an unwanted protein) is observed only with the
      antisense sequence and weakly, if at all, with any of the control sequences, this
      is a necessary but not a sufficient condition to demonstrate an antisense effect.
      Indeed, biochemical parameters such as stability, uptake and subcellular
      compartmentalization of ODN in a given cellular system are most often sequence
      dependent processes. In this work, a series of phosphorothioate ODN of different
      lengths and sequences were evaluated as to their binding, internalization and
      subcellular distribution properties in vascular smooth muscle cells. In addition
      to membrane binding and nuclear accumulation, the partition of ODN in the cytosol
      of cells was measured by a method based upon controlled permeabilization of the
      plasma membrane, permitting the recovery of the cytosolic content with minimal
      damage to the membranes of the endocytic vesicles and lysosomes. We found that
      the tested ODN showed striking differences in their uptake and distribution in
      smooth muscle cells. Our results gave rise to the problem of validating the
      observed biological effects when different sequences of ODN were compared.
      Cellular studies such as the one presented in this work could help in choosing
      the proper control sequences among ODN exhibiting similar cell interactions as
      compared to the antisense sequences. Moreover, this method could be useful for
      the selection of antisense sequences that can be efficiently internalized and
      preferentially distributed in the appropriate compartments in cells for in vitro
      antisense studies.

PMID- 10076540
TI  - Cellular distribution of N-acetyltransferase activity in the rat small intestine.
AB  - The cellular distribution of AcCoA:arylamine N-acetyltransferase (NAT; EC
      2.3.1.5) activities was examined in the rat small intestine to determine if
      heterogeneous cellular distribution contributes to preferential tumor development
      in the colonic region after exposure to heterocyclic amines (HAs). A
      chelation/elution method was used to preferentially isolate villus-tip, mid
      villus, and crypt enterocytes. Monomorphic (NAT1) and polymorphic (NAT2)
      activities were determined using N-acetylprocainamide and N-acetamidobenzoic acid
      formation, respectively. Sucrase-isomaltase (SI) activity was used to confirm
      that a villus, mid-villus, and crypt cell gradient had been obtained. Utilizing
      this marker of villus enrichment, a 4- to 10-fold gradient was achieved. NAT1 and
      NAT2 activities followed this gradient, with the highest NAT activity occurring
      in the fraction with the highest SI activity. The ratio of NAT2:NAT1 remained
      essentially constant along the gradient, indicating a similar pattern of
      expression for both enzymes. This pattern of cellular distribution for the NATs
      is similar to that reported for cytochrome P450s. This apparent preferential
      expression of NAT in the villus cells may result in delivery of bioactivated HAs
      to the lower regions of the intestines as the villus-tip cells are extruded into
      the intestinal lumen and enter the fecal stream.

PMID- 10076541
TI  - Consequences of overexpression of growth hormone in transgenic mice on liver
      cytochrome P450 enzymes.
AB  - The effect of growth hormone (GH) on cytochrome P450 (CYP) and P450-dependent
      monooxygenases was studied in 4-, 6-, 8-, and 10-month-old female bovine growth
      hormone (bGH) transgenic mice that overexpress GH. Nontransgenic female mice
      (C57/SJL) littermates were used for baseline determinations. The body weights of
      the bGH mice were approximately 35% greater than those of the controls. The liver
      weights were 2-fold higher than those of the controls, resulting in a 25-60%
      increase in liver/body weight ratio during the life span of the bGH mice when
      compared with the controls. Similar increases in heart and kidney weights were
      observed. Since the GH transgene was transcriptionally regulated by a
      metallothionein-I gene promoter, metallothionein concentrations in livers of
      transgenic and nontransgenic mice were measured. No significant differences were
      observed. In marked contrast to increases in liver weights, hepatic cytochrome
      P450 content, benzphetamine N-demethylase, and benzo [a] pyrene hydroxylase
      activities were decreased by 36, 42 and 75%, respectively. No age-related changes
      in the decrease of the monooxygenases were observed. Microsomal heme oxygenase
      (HO) in the liver was induced 44% above the control values. Immunoblot analysis
      also showed a marked increase in HO-1 in the bGH mice. These results indicate
      that GH suppresses the carcinogen-metabolizing enzyme benzo [a] pyrene
      hydroxylase and the drug-metabolizing enzyme benzphetamine N-demethylase. This
      suppression was accompanied by an induction of HO activity in bGH transgenic
      mice. The consequences of prolonged exposure to supraphysiological levels of this
      hormone cannot always be predicted from the known physiological actions of GH.

PMID- 10076542
TI  - Inhibition by aminosalicylates of phosphatidic acid formation induced by
      superoxide, calcium or spermine in enterocyte mitochondria.
AB  - Inflammation is associated with oxidative stress and altered cellular calcium
      homeostasis. Our earlier studies have shown that, increased phosphatidic acid
      (PA) formation occurred in enterocyte mitochondria when exposed to superoxide,
      divalent metal ions or polyamines resulting in altered lipid composition. Since
      aminosalicylates are the drug of choice for gut inflammation, we have tested the
      effect of aminosalicylates on PA formation by enterocyte mitochondria. When
      stimulated by superoxide, Ca2+ or spermine, phosphatidyleth-anolamine (PE)
      degradation and PA formation occurred in enterocyte mitochondria which can be
      inhibited by aminosalicylates. The inhibition was 50-60% at 0.5-mM concentration
      and at 1- or 2-mM final concentration, complete inhibition was observed. Both 5
      aminosalicylate (5-ASA) and 4-aminosalicylate (4-ASA) showed similar effects. The
      stimulation of PA formation by calcium or spermine was not due to increased
      generation of superoxide by mitochondria which was confirmed by measurement of
      superoxide production by the mitochondria. These studies suggest that in addition
      to other cellular effects, aminosalicylates may prevent the enterocyte
      mitochondrial damage by inhibition of PA formation and PE degradation and
      alteration of mitochondrial lipid composition.

PMID- 10076543
TI  - Ascorbic acid-dependent cytoprotection of ovarian cells by leukocyte and
      nonleukocyte peroxidases.
AB  - Luteal cells contain high levels of ascorbic acid that is secreted by stimulation
      with agents like luteinizing hormone (LH) and prostaglandin F2 alpha (PGF2
      alpha). One role for interstitial ascorbic acid, we propose, may be the
      detoxification of H2O2 by regeneration of catalytically active peroxidase. By
      serving as a preferred secondary substrate, ascorbic acid regenerates the
      catalytically active peroxidase that is inhibited irreversibly by H2O2 alone. To
      test this hypothesis, luteal cells were incubated in the absence and presence of
      peroxidases and H2O2, and the maximal cyclic AMP and steroidogenic response to LH
      was examined. In luteal cells, H2O2 is known to severely inhibit LH-sensitive
      cyclic AMP accumulation and steroidogenesis, and the addition of lactoperoxidase,
      myeloperoxidase, eosinophil peroxidase, or ascorbic acid (1 mM) alone had no
      effect on these responses to H2O2. However, co-incubation of ascorbic acid and
      the peroxidases completely reversed the inhibition of cyclic AMP accumulation and
      steroidogenesis produced by H2O2. These findings and the results that show direct
      oxidation of ascorbic acid in the presence of peroxidase and H2O2, but not with
      H2O2 alone, support the conclusion that ascorbic acid released from cells may
      detoxify H2O2 by regenerating the catalytically active state of peroxidases.

PMID- 10076544
TI  - Characterization of folate transport mediated by a low pH route in mouse L1210
      leukemia cells with defective reduced folate carrier function.
AB  - Folate influx at low pH was characterized in MTXrA cells, an L1210 mouse leukemia
      cell line with a functional defect in the reduced folate carrier. Folic acid
      influx in MTXrA cells was negligible at pH 7.5, increased 13-fold as the pH was
      decreased to 6.0, and was indistinguishable from that in L1210 cells. In
      contrast, while methotrexate (MTX) influx in MTXrA cells at pH 6.0 was 15-fold
      higher than at pH 7.5, in L1210 cells it was decreased by half. Influx of MTX,
      folic acid, 5-methyltetrahydrofolate and 5-formyltetrahydrofolate in MTXrA cells
      was increased at pH < 7.0, but their pH optima and profile differed
      substantially. Influx of MTX and 5-methyltetrahydrofolate at pH 6.0 showed
      saturability, with a Kt of 2.65 and 0.56 microM, and a Vmax of 0.45 and 0.083
      nmol/g dry wt/min, respectively. MTX influx mediated by the low pH transporter
      was insensitive to the anionic composition of the transport buffer and affected
      minimally (approximately 20%) by Na+ substitution. The anion transport inhibitors
      sulfobromophthalein, diisothiocyanatostilbene disulfonic acid, and
      acetamidoisothiocyanatostilbene disulfonic acid were not effective inhibitors of
      the low pH route. MTX transport at low pH did not increase in MTXrA-R16 cells, an
      MTXrA derivative with 10-fold overexpression of the reduced folate carrier (RFC)
      due to transfection with RFC1 cDNA. Inhibition of reduced folate carrier activity
      with acetamidoisothiocyanatostilbene disulfonic acid resulted in identical MTX
      influx in L1210, MTXrA, and MTXrA-R16 cells at pH 5.5. Finally, low pH-mediated
      MTX influx was reduced by energy inhibitors and partially inhibited by ionophores
      (nigericin > monensin >> valinomycin). The data indicate that L1210 and MTXrA
      cells express similar activities of a low pH folate transporter that has
      properties distinct from, and independent of, the reduced folate carrier.

PMID- 10076545
TI  - Induction time course of cytochromes P450 by phenobarbital and 3
      methylcholanthrene pretreatment in liver microsomes of Alligator
      mississippiensis.
AB  - Alligator mississippiensis has at least two classes of inducible hepatic
      microsomal cytochromes P450 (CYP): (1) those induced by 3-methylcholanthrene
      (3MC), and (2) those induced by phenobarbital (PB). The rates of induction by
      these xenobiotic compounds are significantly slower than those reported for
      mammals. Carbon monoxide binding, western blots, and enzymatic activity
      measurements indicated that at least 48-72 hr are required to reach full
      induction. A methoxy-, ethoxy-, pentoxy, and benzyloxyphenoxazone (resorufin) O
      dealkylation (MROD, EROD, PROD, and BROD) profile was indicative of substrate
      selectivity typical of 3MC- and PB-induced P450s. MROD and BROD showed the
      greatest ability to discriminate between alligator hepatic microsomes induced by
      3MC and PB, respectively. This is in contrast to mammals, in which EROD is a
      biomarker of polycyclic aromatic hydrocarbon exposure because of its ability to
      discriminate the induction of CYP 1A. In a similar manner, PROD is a highly
      preferred activity of CYP 2B in mammals; thus, it is used to indicate CYP 2B
      induction. The induction of P450 by PB is a general phenomenon in mammals and
      birds. To the best of our knowledge, this is the first report demonstrating PB
      induction of P450 activities typical of the mammalian CYP 2 family isoforms in
      alligator or any reptilian liver. The importance of this finding to the evolution
      of CYP 2 family regulation by PB is heightened by the fact that induction by this
      xenobiotic is not common to fish and other lower vertebrates (Ertl RP and Winston
      GW, Comp Biochem Physiol, in press). Although indicating the presence of CYP 1A-
      and CYP 2B-like isoforms in alligator, it remains to be established how closely
      related these alligator P450s are to mammalian isoforms.

PMID- 10076546
TI  - Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4
      trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the
      physiologically active metabolite of the novel immunomodulator leflunomide.
AB  - N-(trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the
      physiologically active metabolite of leflunomide, has been described to exert
      antiproliferative effects in vitro and anti-inflammatory actions in several
      animal models. Currently, its use is being evaluated in clinical trials in
      psoriasis, which is characterized by epidermal hyperproliferation and
      infiltration of inflammatory cells. We studied the effects of A77 1726 on growth
      and gene expression in cultured epidermal cells by 5-bromo-2'-deoxy-uridine
      (BrdU) incorporation, reverse transcriptase-polymerase chain reaction (RT-PCR),
      Northern blot hybridizations and flow cytometry. A77 1726 inhibited epidermal
      proliferation at concentrations above 5 microM after 24 hr. However, the cells
      were still fully viable at a concentration of 100 microM. The drug caused a dose
      dependent reduction in the mRNA level of the type A receptor for the
      proinflammatory cytokine interleukin-8 (IL-8-RA) and, in contrast, induced gene
      expression of the receptor for the anti-inflammatory cytokine IL-10 (IL-10R) at
      the mRNA and protein levels. In addition, the mRNA and protein levels of the p53
      gene, which is a negative cell cycle regulator, were up-regulated by A77 1726.
      These data suggest that A77 1726 exerts its anti-inflammatory action via the
      modulation of epidermal gene expression.

PMID- 10076547
TI  - Quantitative analysis of the high-affinity binding sites for [3H]ouabain in the
      rat vas deferens and their immunological identification as the alpha 2 isoform of
      Na+/K(+)-ATPase.
AB  - Binding assays were performed with [3H]ouabain to investigate the presence of,
      and to characterize, a Na+/K(+)-ATPase isoform with high affinity for cardiac
      glycosides in the rat vas deferens. Nonlinear regression analysis of equilibrium
      experiments carried out with crude preparations in a Mg-Pi medium indicated the
      presence of high-affinity sites characterized with good precision (individual
      coefficients of variation = 11-35%) by their density (Bmax = 0.42 to 0.72 pmol/mg
      protein) and dissociation constant (Kd = 0.069 to 0.136 microM) values. The
      values of the dissociation rate constant (kappa-1) and the association rate
      constant (kappa+1) for these sites were 0.151 to 0.267 min-1 and 2.87 to 3.60
      microM-1.min-1, respectively. A higher number of low-affinity sites (Kd around 15
      microM), supposed to correspond to the alpha 1 isoform, was also identified, but
      their Kd and Bmax values were not quantified precisely in this crude preparation.
      Western blot assays indicated hybridization with specific anti-alpha 1 and anti
      alpha 2 isoform antibodies but not with anti-alpha 3 isoform antibody. Taken
      together, the present results indicate the existence of a low proportion of the
      alpha 2 isoform of Na+/K(+)-ATPase in the rat vas deferens that can be quantified
      precisely by [3H]ouabain binding even in a crude membrane preparation that is
      suitable for studies under conditions of plasticity.

PMID- 10076548
TI  - Functional blockade of opioid analgesia by orphanin FQ/nociceptin.
AB  - Orphanin FQ/nociceptin (OFQ/N) is a recently identified neuropeptide with high
      affinity for the orphan opioid receptor. OFQ/N blocked morphine analgesia in mice
      in a dose-dependent manner, as well as the analgesic actions of [D-Pen2, D
      Pen5]enkephalin (DPDPE), morphine-6 beta-glucuronide, trans-3,4-dichloro-N-[2-(1
      pyrrolindinyl)-cyclohexyl]-benzeneac eta mide, methane sulfonate hydrate
      (U50,488H) and naloxone benzoylhydrazone. These actions are anti-analgesic,
      because OFQ/N also blocked clonidine analgesia and OFQ/N was inactive against the
      inhibition of gastrointestinal transit by morphine. Although OFQ/N was quite
      potent in these paradigms, two truncated forms, OFQ/N(1-11) and OFQ/N(1-7), were
      inactive. An antisense oligodeoxynucleotide targeting the first coding exon of
      KOR-3, the mouse homolog of the orphan opioid receptor, effectively prevented the
      anti-opioid actions of OFQ/N, confirming the importance of the orphan opioid
      receptor in this action.

PMID- 10076549
TI  - [13C-mixed triglyceride CO2 exhalation test. Investigation with an isotope
      selective, non dispersive infrared spectrophotometer of indirect function of the
      exocrine pancreas].
AB  - BACKGROUND AND OBJECTIVE: The 13C-mixed-triglyceride CO2-exhalation test (MTE)
      has been proposed for the noninvasive assessment of intraluminal duodenal
      pancreatic lipase activity. Up to now, stable isotope analysis of carbon dioxide
      of the MTE has been carried out with isotope ratio mass-spectrometry. The aim of
      the present study was to evaluate the MTE in patients with morphological signs of
      chronic pancreatitis (stages I-III) and exocrine pancreatic insufficiency by
      using an isotope-selective nondispersive infrared spectrometer (NDIRS). PATIENTS
      AND METHODS: 20 healthy volunteers (9 females, 11 males, age range 19-61 years)
      and 16 patients (7 females, 9 males, age range 33-76 years) were examined. After
      an overnight fast each patient received a solid-liquid test meal containing 250
      mg 1,3 distearyl, 2[13C] octanoyl glycerol. Breath samples were obtained at
      baseline and at 30 min intervals over a period of 6 h after the test meal. The
      13C/12C isotope ratio in each breath sample was determined by NDIRS as delta (%)
      and delta over baseline (%). Results were expressed as cumulative percentage dose
      of 13C recovered (cPDR) at 3, 4, 5, 6 h and maximal PDR (PDRpeak) (median; 5./95.
      percentile). RESULTS: Significant lower values concerning cPDR 3, 4, 5, 6 hours
      and PDRpeak [%] were found between healthy subjects and patients with chronic
      pancreatitis (p < 0.05): cPDR 6 h: 8.1 (0.4-20.5)% vs 29.1 (10.3-59.3)%; PDRpeak:
      4.7 (0.4-10.2)% vs 9.2 (5.4-14.3)%. INTERPRETATION: In general, the MTE
      discriminates between healthy controls and patients with chronic pancreatitis and
      exocrine pancreatic insufficiency. However, the MTE using NDIRS cannot be
      recommended as a method of clinical routine because of marked data overlap
      between pathologic and normal values.

PMID- 10076550
TI  - [Primary palliative treatment of malignant gastric outlet obstruction with a self
      expanding metal stent].
AB  - BACKGROUND AND OBJECTIVE: A high operative mortality, diffuse local tumor growth
      and abnormal wound healing are significant risk factors in the palliative
      surgical treatment of gastric outlet obstruction caused by a malignant tumor.
      This study was undertaken to evaluate the use of self-expanding metal stents as
      an alternative. PATIENTS AND METHODS: Over a period of 33 months, nine previously
      unoperated patients (three women, six men; mean age 71.4 [66-76] years) with
      gastric outlet obstruction by a malignant tumor underwent endoscopic implantation
      of an uncoated self-expanding nitinol Ultraflex stent. The stent's length was 7
      and 10 cm, respectively, the length of the carrier catheter was 92 cm. The stent
      was implanted after balloon dilatation of the stenosis and marking the distal
      tumor margin with lipiodol injected over a guide-wire under fluoroscopic control.
      RESULTS: The implantation was successful in only two of the first five patients,
      but after modifying the method of stent release in three of the four subsequent
      patients. All patients reported an improved quality of life. One patient died
      after 10 days of the underlying malignancy. There were no complications
      associated with the implantation. CONCLUSIONS: Insertion of a self-expanding
      metal stent can provide palliation in patients with inoperable gastric outlet
      stenosis due to malignant tumour. The number of successful implantations can
      probably be increased by optimizing some of the devices used, for example by
      lengthening the carrier catheter.

PMID- 10076551
TI  - [Vertebral destruction with sever pain in the SAPHO syndrome].
AB  - HISTORY AND ADMISSION FINDINGS: A 57-year-old man had for the past 18 months
      complained of recurrent, recently worsening, belt-like backache radiating
      ventrally. On admission a skin rash consisting of blister and pustules was noted
      on the palms of both hands. He had pain on pressure over the right upper abdomen,
      an enlarged prostate and definite pain on percussing the vertebral column with
      restricted movement of the thoracic vertebral column, but no other physical
      signs. INVESTIGATIONS: Radiology revealed clearly increased sclerosis of several
      thoracic vertebrae with osteolytic destruction and a paravertebral soft tissue
      tumor. Search for a primary tumor was unsuccessful. Bone scintigraphy
      demonstrated nuclide enrichment of the thoracic vertebrae and of the
      sternoclavicular joints without increase in the LeukoScan. These findings
      indicated the diagnosis of SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis
      osteomyelitis). TREATMENT AND COURSE: Rapid subjective and objective improvement
      followed the administration of clindamycin and ibuprofen. CONCLUSION: In case of
      bone pain of uncertain aetiology, especially when associated with skin rash, the
      rare SAPHO syndrome should be considered in the differential diagnosis, avoiding
      lengthy diagnostic steps and allowing early treatment.

PMID- 10076552
TI  - [Therapeutic influences on angiogenesis. "From bench to bedside"].

PMID- 10076553
TI  - [Diagnosis and treatment of Alzheimer-type dementia].

PMID- 10076554
TI  - [Judicial rights of patients in health facilities. Overview of current state of
      jurisdiction].

PMID- 10076555
TI  - [Therapy of secondary hyperparathyroidism].

PMID- 10076556
TI  - [Latent autoimmune diabetes mellitus].

PMID- 10076557
TI  - Trends of lung cancer incidence by histologic types in Japan.

PMID- 10076558
TI  - Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene
      in the same allele in a patient with multiple endocrine neoplasia type 2B without
      codon 918 mutation.
AB  - Multiple endocrine neoplasia (MEN) type 2B is a clinically distinct entity among
      the autosomal dominant MEN 2 syndromes. Most patients with MEN 2B carry a
      germline mutation (M918T) of the RET proto-oncogene, while a few carry A883F. We
      examined a patient with MEN 2B, but without M918T or A883F, and her relatives.
      Here, we report the presence in this patient of 2 germline mutations, V804M and
      Y806C in the same allele. While the novel Y806C was inherited from her father,
      its carriers (her father and brother) was not affected by MEN 2. In contrast,
      V804M was a de novo mutation, that has been reported in patients with familial
      medullary thyroid carcinoma. Combinations of mutations of the RET proto-oncogene
      may cause oncogenic activities different from those of single mutations.

PMID- 10076559
TI  - Trends of lung cancer incidence by histologic type: a population-based study in
      Osaka, Japan.
AB  - We investigated trends of lung cancer incidence from 1974 to 1993 by histologic
      type, using data from the population-based cancer registry in Osaka, Japan. Since
      the proportion of cases with histologic types identified was not sufficiently
      high, sex- and age-specific incidence rates by histologic types were estimated
      assuming that the distribution of histologic types was the same across the same
      sex and age group regardless of reporting status. Cumulative risk from 0 to 74
      years old for total lung cancer increased 1.3-fold from the period 1974-77 to
      1986-89 and then plateaued in the period 1990-93 for both males and females. When
      divided into histologic types, cumulative risk for incidence of squamous cell
      carcinoma was almost constant during the study period for both males and females.
      During the same period, adenocarcinoma increased up to 1.4-fold for both males
      and females. This increase seemed to have reached a plateau recently for males,
      but not for females. Small cell carcinoma increased monotonously up to 1.6- to
      1.7-fold for both males and females. Large cell carcinoma showed over 2-fold
      increase for both males and females; however, the estimates fluctuated due to the
      small number of cases. This study provides further evidence of a relative
      increase of adenocarcinoma compared to squamous cell carcinoma. Recent trends of
      tapering increase of lung cancer incidence should be confirmed by further
      observation.

PMID- 10076560
TI  - Promotion by sodium L-ascorbate in rat two-stage urinary bladder carcinogenesis
      is dependent on the interval of administration.
AB  - In our two-stage model of rat urinary bladder carcinogenesis employing N-butyl-N
      (4-hydroxybutyl)nitrosamine (BBN) as the initiator, sodium L-ascorbate (Na-AsA)
      exhibits dose-dependent promotion. In the present study, in order to assess the
      possible reversibility of the promoting effects, we investigated how different
      administration periods of Na-AsA influence its promoting activity. In experiment
      1, rats were treated with 5% Na-AsA for different administration periods with or
      without withdrawal and injected with 5-bromo-2'-deoxyuridine (BrdU) to allow
      determination of the cell proliferation status. Replicative DNA synthesis in the
      urinary bladder epithelium was shown to return to normal after removal of the
      promoting stimulus. In experiment 2, rats were initially given BBN for 4 weeks
      and subsequently received 16 weeks of Na-AsA, alternating with basal diet, at
      intervals of 4, 8 or 16 weeks, within a total 32-week period. The longer the
      continuous exposure to Na-AsA, the greater the yield of papillomas and carcinomas
      in the urinary bladder. In experiment 3, Na-AsA was given for 4 or 8 weeks after
      BBN initiation and the animals were killed at weeks 8 and 12. Both promotion of
      lesion development and increase of DNA synthesis in the urinary bladder
      epithelium were dependent on the length of exposure to Na-AsA and the total
      period of exposure. The results indicate that the promoting effects of Na-AsA in
      urinary bladder carcinogenesis are reversible to a certain extent after its
      withdrawal, and the existence of a cumulative exposure time threshold seems
      likely.

PMID- 10076561
TI  - Development of androgen-independent carcinomas from androgen-dependent
      preneoplastic lesions in the male accessory sex organs of rats treated with 3,2'
      dimethyl-4-aminobiphenyl and testosterone propionate.
AB  - Two kinds of cancer can be induced in rat male accessory sex organs, one a non
      invasive carcinoma arising in the ventral lobe and the other an invasive lesion
      which develops in the dorsolateral and anterior lobe as well as the seminal
      vesicles. In the present study, one group of male rats were given biweekly s.c.
      injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 weeks for induction of
      non-invasive carcinomas and the other group received DMAB with 40-week
      testosterone propionate for induction of invasive carcinomas. Half of the animals
      in each group were then subjected to bilateral orchiectomy at week 41 to remove
      testicular androgen, in order to examine the androgen dependence of both types of
      carcinomas as well as precancerous lesions. Animals were killed at weeks 41, 46
      and 60. All parts of the prostate complex showed involution and significant
      weight reduction after castration, with a complete disappearance of atypical
      hyperplasias and carcinomas of the ventral prostate. However, in spite of
      suppression of development of atypical hyperplasias in the anterior prostate and
      seminal vesicles, the incidence of invasive carcinomas was not changed. Normal
      epithelial cells and atypical hyperplasias of all parts of the prostate and
      seminal vesicles and carcinomas of the ventral prostate were
      immunohistochemically positive for nuclear androgen receptor, while invasive
      carcinomas that developed in either castrated or non-castrated animals were
      negative. These findings suggest that in the ventral prostate, both precancerous
      and cancerous lesions are androgen-dependent, but in the anterior and seminal
      vesicles, cancerous lesions (invasive carcinomas) are androgen-independent while
      precancerous lesions are hormone-dependent.

PMID- 10076562
TI  - Modulating effects of diets high in omega-3 and omega-6 fatty acids in initiation
      and postinitiation stages of diethylnitrosamine-induced hepatocarcinogenesis in
      rats.
AB  - The effects of sardine fish oil or corn oil on diethylnitrosamine (DEN)-induced
      hepatocarcinogenesis were investigated in male F344 rats. Starting at 5 weeks of
      age, animals were divided into 11 groups and fed 23.5% corn oil (HCO) (groups 1
      and 7) or 5% corn oil (LCO) (groups 2 and 8), 22.5% sardine oil + 1% corn oil
      (FO) semipurified diet (groups 3 and 9) or basal diet (CE-2) (groups 4-6, 10 and
      11). At 6 weeks of age, all animals except the vehicle-treated groups were given
      DEN (200 mg/kg body weight, i.p. once weekly for 3 weeks). One week after the
      final exposure to DEN, groups 1-3 were changed to the basal diet, and groups 4-6
      were switched to the HCO, LCO or FO diet, respectively. Animals in groups 1-3 and
      10 were given drinking water containing 0.05% phenobarbital (PB). Liver sections
      from the animals at the termination of the experiment (24 weeks) were doubly
      stained for glutathione S-transferase placental form (GST-P) and silver-stained
      nucleolar organizer regions (AgNORs). The multiplicity of hepatocellular
      neoplasms of group 1 was significantly larger than that of group 2 or 3. The
      number of GST-P-positive foci of group 2 or 3 was significantly smaller than that
      of group 1. Among the groups fed the experimental diets in the postinitiation
      phase (groups 4-6), no significant difference was found in the incidence of liver
      tumors. AgNORs values of the enzyme-altered foci in rats of the HCO diet groups
      were larger than those of the other diet groups. These results indicate that the
      enhancing effect of a high dose of corn oil in hepatocarcinogenesis is mainly
      present during the initiation phase but not during postinitiation phase, and fish
      oil rich in polyunsaturated omega-3 fatty acids could inhibit DEN-induced
      hepatocarcinogenesis in rats.

PMID- 10076563
TI  - Analysis of the c-myc, K-ras and p53 genes in methylcholanthrene-induced mouse
      sarcomas.
AB  - We have examined 63 methylcholanthrene (MCA)-induced mouse sarcomas for possible
      correlations of mutations involving the c-myc, ras and p53 genes. The c-myc gene
      was found to be amplified in 18 of these sarcomas (29%). Polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) analysis and
      subsequent direct sequencing identified 18 cases carrying K-ras mutation at
      codons 12, 13 and 61 (29%). No mutation was detected in the H-ras and N-ras
      genes. Mutations of the p53 gene in exons 5 to 8 were found in 45 cases (71%).
      Comparison of these mutations revealed that out of 18 cases with c-myc gene
      amplifications, 10 carried K-ras mutations (56%) and 14 carried p53 mutations
      (78%). In contrast, among 45 cases of sarcomas without c-myc gene amplification,
      8 were found to have K-ras mutations (18%). The same 45 cases were found to have
      31 p53 mutations (69%). The present study suggests a strong correlation between c
      myc gene amplification and K-ras gene mutation (P < 0.01). p53 gene mutation was
      frequently found among MCA-induced mouse sarcomas, indicating the importance of
      this mutation in the etiology of these tumors. However, p53 mutations were
      present in sarcomas regardless of the state of c-myc amplification and K-ras
      mutation. Therefore, a defect in the p53 gene is independent of amplification of
      the c-myc gene or point mutation of the K-ras gene.

PMID- 10076564
TI  - Human T-cell leukemia virus type 1 can infect a wide variety of cells in mice.
AB  - Analysis of human T-cell leukemia virus type 1 (HTLV-1)-infected cell types and
      the interplay of these infected cells in vivo should provide valuable information
      to elucidate the pathogenesis of HTLV-1-associated diseases in humans and in
      animal models. In this study, HTLV-1-infected cell types were identified in HTLV
      1-infected C3H/HeJ mice. Pan T, CD4+, CD8+, granulocyte and pan B cell fractions
      in the splenocytes of MT-2 cell-inoculated mice were sorted by use of their cell
      surface high-density expression of CD3e, CD4, CD8, Gr-1 and B220 antigens,
      respectively, with a fluorescence-activated cell sorter. The pX sequence of HTLV
      1 provirus in the lysate of each fraction was amplified by polymerase chain
      reaction and detected by Southern hybridization. Interestingly, in addition to
      the CD4+ cell fraction, the pX sequence was also found in CD8+ cell, B cell and
      granulocyte fractions. The broad cell spectrum of HTLV-1 infection in mice is
      consistent with the situation in humans. Our finding indicate that HTLV-1
      receptor or coreceptor is widely distributed among different cell types in mice.

PMID- 10076565
TI  - Mutations of the beta-catenin gene in endometrial carcinomas.
AB  - To investigate the contribution of beta-catenin to the development of endometrial
      carcinoma, we searched for genetic alterations of the beta-catenin gene in
      primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin
      gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was
      performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors
      (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential
      GSK-3 beta phosphorylation sites. Each of the mutations resulted in the
      substitution of serine/threonine residues that have been implicated in the down
      regulation of beta-catenin through phosphorylation by GSK-3 beta kinase.
      Furthermore, the incidence of beta-catenin mutations was significantly higher in
      early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014,
      Fisher's exact test). Replication error (RER)-positive phenotype was not detected
      in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed
      RER. We performed immunohistochemistry of beta-catenin in 17 cases for which
      tissue samples were available. We confirmed accumulation of beta-catenin protein
      in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid
      alterations had occurred at codon 33 and 37. The other case had no mutation in
      exon 3. Our results suggested that mutations at serine/threonine residues
      involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin.
      Accumulation of mutant beta-catenin could contribute to the development of a
      subset of endometrial carcinomas, particularly those of the early-onset type.

PMID- 10076566
TI  - Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine
      protein kinases and heat shock protein HSP90 in human hematopoietic cell lines.
AB  - A proto-oncogene, MTG8 (ETO/CDR), is disrupted in the t(8;21) translocation
      associated with acute myeloid leukemia, and the gene product, MTG8, is a
      phosphoprotein capable of cell transformation in concert with v-H-ras. To obtain
      insight into functional regulation of MTG8 by phosphorylation, we studied protein
      kinases that interact with, and phosphorylate, MTG8 in vitro. Recombinant MTG8
      protein was first found to be associated with two serine/threonine protein
      kinases in cell extracts from both HEL cells and a leukemic cell line carrying
      t(8;21). A cytoplasmic protein kinase of 61 kDa (MTG8N-kinase) phosphorylated the
      amino-terminal of MTG8, and another of 52 kDa (MTG8C-kinase) phosphorylated the
      carboxyl-terminal domain. In addition, we demonstrated that heat shock protein 90
      (HSP90) specifically binds to the amino-terminal domain of MTG8 in vitro and in
      vivo. Thus, our results shed new light on post-translational regulation of MTG8,
      perturbation of which, in AML1-MTG8 protein, probably contributes to
      leukemogenesis.

PMID- 10076567
TI  - Growth inhibition of A549 human lung adenocarcinoma cells by L-canavanine is
      associated with p21/WAF1 induction.
AB  - L-Canavanine (CAV) is a higher plant nonprotein amino acid and a potent L
      arginine antimetabolite. CAV can inhibit the proliferation of tumor cells in
      vitro and in vivo, but little is known regarding the molecular mechanisms
      mediating these effects. We demonstrated that the treatment of human lung
      adenocarcinoma A549 cells with CAV caused growth inhibition; G1 phase arrest is
      accompanied by accumulation of an incompletely phosphorylated form of the
      retinoblastoma protein, whose phosphorylation is necessary for cell cycle
      progression from G1 to S phase. In addition, CAV induces the expression of p53
      and subsequent expression of a cyclin-dependent kinase inhibitor, p21/WAF1. The
      p53-dependent induction of p21/WAF1 and the following dephosphorylation of the
      retinoblastoma protein by CAV could account for the observed CAV-mediated G1
      phase arrest.

PMID- 10076568
TI  - Peroxisome proliferator-activated receptor gamma induces growth arrest and
      differentiation markers of human colon cancer cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR gamma), one of the nuclear
      receptors expressed in adipose tissue, plays an important role in adipocyte
      differentiation. In this study, we investigated the expression of PPAR gamma and
      its role in cellular growth and differentiation in six colon cancer cell lines:
      HT-29, CaCo-2, SW-480, DLD-1, LoVo, and T-84. All six expressed PPAR gamma mRNA
      and protein, shown respectively on northern and western blot analyses. Luciferase
      assay in HT-29 cells, which strongly express PPAR gamma, showed that
      troglitazone, a selective ligand for PPAR gamma, transactivated the transcription
      of a peroxisome proliferator response element (PPRE)-driven promoter.
      Furthermore, troglitazone caused a marked decrease in [3H]thymidine incorporation
      and G1 cell-cycle arrest determined by flow cytometry. Finally, troglitazone
      induced expression of mRNAs for villin and intestinal alkaline phosphatase,
      markers for enterocyte differentiation. In conclusion, human colon cancer cells
      express PPAR gamma, the ligands of which inhibit cell growth and induce
      differentiation markers.

PMID- 10076569
TI  - Low glutathione and glutathione S-transferase levels in Barrett's esophagus as
      compared to normal esophageal epithelium.
AB  - Patients with Barrett's esophagus, wherein squamous epithelium has been replaced
      by columnar epithelium, have an increased risk for developing esophageal
      adenocarcinoma as compared to the general population. Glutathione S-transferase
      (GST), a family of detoxification enzymes consisting of class alpha, mu, pi, and
      theta isoforms, is involved in detoxification of carcinogens and low levels of
      these enzymes correlated with high cancer risk. We have now compared GST enzyme
      activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's
      mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98
      patients with Barrett's esophagus were taken from both Barrett's and adjacent
      normal squamous epithelium. GST enzyme activity towards 1-chloro-2,4
      dinitrobenzene was measured, and GST isoenzyme levels were determined by
      densitometrical analyses of western blots after immunodetection with monoclonal
      antibodies. Total GSH content was determined by high-performance liquid
      chromatography after conjugation with monobromobimane. Wilcoxon's signed rank
      test and Spearman correlation analyses were used for statistical evaluation. As
      compared with adjacent normal squamous epithelium, GST enzyme activity in
      Barrett's epithelium was reduced by 35%, and GST mu, GST pi and GSH levels were
      reduced by 24%, 30%, and 63%, respectively. However, the minor GST alpha and GST
      theta levels were higher in Barrett's epithelium (by 625% and 33%, respectively).
      High levels of GSH and GSTs in general are correlated with protection against
      cellular or cytogenetic damage. The observed reduction in GSTs and GSH in
      Barrett's epithelium may therefore contribute to the increased cancer risk in
      this tissue.

PMID- 10076570
TI  - Differential regulation of MMP-9 and TIMP-2 expression in malignant melanoma
      developed in metallothionein/RET transgenic mice.
AB  - We recently established a metallothionein-I(MT)/RET transgenic mouse line in
      which skin melanosis, benign melanocytic tumor and malignant melanoma develop
      stepwise. Malignant melanoma cells but not benign melanocytic tumor cells had
      metastatic ability in transgenic mice. In the present study, we investigated the
      expression of several matrix metalloproteinases (MMPs) and tissue inhibitors of
      matrix metalloproteinases (TIMPs), including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9,
      MT1-MMP, TIMP-1 and TIMP-2, in these tumors. Western and northern blot analyses
      revealed that malignant transformation of melanocytic tumors developed in MT/RET
      transgenic mice accompanied with upregulation of MMP-9 and downregulation of TIMP
      2. Expression of other MMP and TIMP genes examined was very low or undetectable
      in both benign and malignant tumors. Since activation of MMP-9 in malignant
      tumors was detected by gelatin zymography, these results suggest that imbalance
      of expression of the MMP-9 and TIMP-2 genes might be associated with metastatic
      ability of melanoma cells developed in MT/RET transgenic mice.

PMID- 10076571
TI  - Wide spectrum of antitumor activity of a neutralizing monoclonal antibody to
      human vascular endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF) is known as an angiogenic factor for
      tumor angiogenesis. We developed a neutralizing anti-VEGF monoclonal antibody
      (MAb), MV833, and examined its antitumor activity against 27 human tumor cell
      lines transplanted in nude mice. All the tumor cell lines used in this study
      secreted various amounts of VEGF into culture medium in vitro. However, the
      growth of the cell lines, including three which expressed VEGF receptor, was not
      affected by exogenously added MV833 in vitro. All tumor cell lines including
      colon, lung, breast, pancreas, and melanoma, grew subcutaneously in nude mice.
      The growth of HeLa/v5, which had been transformed by human VEGF121 gene and
      secreted large amounts of VEGF, was significantly faster than that of the control
      vector transformant. Although the amounts of VEGF secreted from two HeLa
      transformants differed greatly, MV833 completely inhibited the growth of both
      tumors. Moreover, the growth of the other 25 human tumor cell lines transplanted
      into nude mice was also strongly suppressed by MV833. Neither the amount of VEGF
      secreted from each tumor cell line in vitro nor the expression of VEGF receptor
      correlated with the antitumor activity of MV833. MV833, administered when tumor
      volumes reached 400 mm3, completely inhibited the growth of some tumor lines. The
      results show VEGF to be a critical angiogenic factor for many tumors. VEGF
      neutralizing antibody could be applicable as an antitumor agent for a wide range
      of tumors.

PMID- 10076572
TI  - Natural killer activity in a medium-term multi-organ bioassay for carcinogenesis.
AB  - Natural killer (NK) cell activity was evaluated after the initiation and
      promotion steps in a medium-term multi-organ bioassay for carcinogenesis. NK cell
      activity was assessed in vitro by Cr51 release assay at the 4th and 30th weeks of
      the experiment. Male Wistar rats were sequentially initiated with N
      diethylnitrosamine (DEN i.p.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN
      drinking water), N-methyl-N-nitrosourea (MNU i.p.), dihydroxy-di-N
      propylnitrosamine (DHPN drinking water) and N,N'-dimethylhydrazine (DMH s.c.) at
      subcarcinogenic doses for 4 weeks (DMBDD initiation). One group was evaluated at
      the 4th week and the other was maintained without any further treatment until the
      30th week. Two initiated groups were exposed through the diet to 2
      acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th
      week. Five additional groups were studied to evaluate the effects of each
      initiator on NK activity. All groups submitted to initiation only, initiation
      plus promotion, or promotion only, developed significantly more preneoplastic
      lesions than the untreated control group. The main target organs for tumor
      development in the initiated animals were the liver and the colon, irrespective
      of treatment with 2-AAF or PB. NK cell activity was not affected by exposure to
      genotoxic carcinogens after initiation, at the 4th week. Treatments only with PB
      or 2-AAF did not change NK cell activity. However, decreased NK cell activity was
      registered in the group only initiated with DMBDD and in the group given DMBDD+2
      AAF. This late depression of NK cell activity at the 30th week could be related
      to the production of suppressing molecules by the tumor cells.

PMID- 10076573
TI  - Enhancement of cisplatin sensitivity in high mobility group 2 cDNA-transfected
      human lung cancer cells.
AB  - To elucidate the role of high mobility group 2 protein (HMG2) in cis
      diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a
      human HMG2-transfected human non-small cell lung cancer cell line, PC-14/HMG2.
      The HMG2 mRNA expression level was approximately twice those of parental PC-14
      and mock-transfected PC-14/CMV. Gel mobility shift assay revealed a CDDP-treated
      DNA-protein complex in the nuclear extract of PC-14/HMG2, which was not found in
      the extracts of PC-14 and PC-14/CMV. This complex formation was subject to
      competition by CDDP-treated non-specific salmon sperm DNA, indicating that
      ectopic HMG2 recognizes CDDP-damaged DNA. PC-14/HMG2 showed more than 3-fold
      higher sensitivity to CDDP than PC-14 and PC-14/CMV. The intracellular platinum
      content of PC-14/HMG2 after exposure to 300 microM CDDP was 1.1 and 1.5 times
      that of PC-14 and PC-14/CMV, respectively. Cellular glutathione levels were not
      different in these cell lines. Repair of DNA interstrand cross-links determined
      by alkaline elution assay was decreased in PC-14/HMG2. These results suggest that
      HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA
      lesion induced by CDDP.

PMID- 10076574
TI  - Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination
      with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer
      cell line TMK-1 in nude mice.
AB  - R-94138, a matrix metalloproteinase inhibitor, was examined for the ability to
      prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. When
      the supernatant of a co-culture of TMK-1 cells and human normal fibroblast cells
      was subjected to gelatin zymography, it was clear that the protein expression of
      MMP-2 had been inhibited by R-94138. When TMK-1 was injected intraperitoneally
      (i.p.) into nude mice at 5 x 10(5) cells/body, the resulting peritoneal
      dissemination mimicked clinical carcinomatous peritonitis. When the maximum
      tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the
      tumor inoculation, peritoneal dissemination was completely inhibited, while the
      effect of R-94138 was limited when it was given i.p. at a dose of 20 mg/kg in a
      schedule of q.d. x 5 starting 12 h after tumor injection. MMC and DDP also
      suppressed peritoneal dissemination when they were administered 1 week after the
      tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R-94138
      inhibited peritoneal dissemination when it was administered i.p. at a dose of 30
      mg/kg in a schedule of q.d. x 5 starting from 1 week after tumor injection. The
      combination of MMC and R-94138 increased the preventive effect on peritoneal
      dissemination. R-94138 seems to be a promising candidate to prevent peritoneal
      dissemination of gastric cancer.

PMID- 10076575
TI  - Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of
      the drug into polymeric micelles.
AB  - For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we
      have successfully incorporated KRN5500 into polymeric micelles. In the present
      study, in vitro and in vivo anti-tumor activity against several human tumor cell
      lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m)
      were evaluated in comparison with those of the prototype KRN5500. KRN/m was found
      to express similar antitumor activity to KRN5500 in the in vitro and in vivo
      systems. However, the vascular damage and liver focal necrosis observed with
      KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore,
      we expect that KRN/m will be superior to KRN5500 for clinical use and that the
      methodology of polymeric micelle drug carrier systems can be applied to other
      water-insoluble drugs.

PMID- 10076576
TI  - Commission report signals the future look of Medicare.

PMID- 10076577
TI  - Food folate vs synthetic folic acid: a comparison.

PMID- 10076578
TI  - Down-board thinking: what are our next moves?

PMID- 10076579
TI  - Past, present, and future perspectives of dietetics practice.

PMID- 10076580
TI  - Influence of obesity on immune function.
AB  - OBJECTIVE: To compare immune function in obese and nonobese subjects. DESIGN:
      Obese and nonobese subjects were compared cross-sectionally. To test for the
      influence of other factors on immunity, aerobic fitness, psychological well
      being, and serum levels of glucose, triglycerides, and cholesterol were measured
      and included in multiple regression models to determine their comparative
      effects. SUBJECTS/SETTING: Community-based subjects included 116 obese women (age
      = 44.3 +/- 9.7 years, body mass index = 33.2 +/- 6.5) and 41 nonobese women (age
      = 42.2 +/- 10.9 years, body mass index = 21.2 +/- 1.9). STATISTICAL ANALYSES
      PERFORMED: Independent t tests, Pearson product moment correlations, and stepwise
      multiple regression procedures. RESULTS: Obesity was linked to elevated leukocyte
      and lymphocyte subset counts (except for natural killer and cytotoxic/suppressor
      T cells), suppressed mitogen-induced lymphocyte proliferation (an index of T- and
      B-cell function), higher monocyte and granulocyte phagocytosis and oxidative
      burst activity, and normal activity of natural killer cells.
      APPLICATIONS/CONCLUSIONS: These data support the contention that obesity is
      associated with alterations in immune function. Further research is needed to
      link immunosuppression with the previously reported elevated risk of infection
      among the obese.

PMID- 10076581
TI  - Behavioral and body size correlates of energy intake underreporting by obese and
      normal-weight women.
AB  - OBJECTIVE: To examine behavioral and body size influences on the underreporting
      of energy intake by obese and normal-weight women. DESIGN: Seven-day estimated
      food records were kept by subjects before they participated in a 49-day
      residential study. Self-reported energy intake was compared with energy intake
      required to maintain a stable body weight during the residential study (reference
      standard). Energy intake bias and its relationship to various body size and
      behavioral measures were examined. SUBJECTS: Twenty-two, healthy, normal-weight
      (mean body mass index [BMI] = 21.3) and obese (mean BMI = 34.2) women aged 22 to
      42 years were studied. STATISTICAL ANALYSES: Analysis of variance, paired t test,
      simple linear regression, and Pearson correlation analyses were conducted.
      RESULTS: Mean energy intake from self-reported food records was underreported by
      normal-weight (-9.7%) and obese (-19.4%) women. BMI correlated inversely with the
      energy intake difference for normal-weight women (r = -.67, P = .02), whereas the
      Beck Depression Inventory correlated positively with the energy intake difference
      for obese women (r = .73, P < .01). CONCLUSION/APPLICATIONS: Results suggest that
      body size and behavioral traits play a role in the ability of women to accurately
      self-report energy intake. BMI appears to be predictive of underreporting of
      energy intake by normal-weight women, whereas emotional factors related to
      depression appear to be more determinant of underreporting for obese women.
      Understanding causative factors of the underreporting phenomenon will help
      practicing dietitians to devise appropriate and realistic diet intervention plans
      that clients can follow to achieve meaningful change.

PMID- 10076582
TI  - Life-course events and experiences: association with fruit and vegetable
      consumption in 3 ethnic groups.
AB  - OBJECTIVE: To examine how life-course experiences and events are associated with
      current fruit and vegetable consumption in 3 ethnic groups. DESIGN: A theoretic
      model developed from previous qualitative research guided the development of a
      telephone survey. Data were collected on fruit and vegetable consumption,
      sociodemographic characteristics, ethnic identity, and life-course events and
      experiences, including food upbringing, social roles, food skills, dietary
      changes for health, and practice of food traditions. SUBJECTS/SETTING: Low- to
      moderate-income adults living in a northeastern US city were selected randomly
      from 3 ethnic groups: black (n = 201), Hispanic (n = 191), and white (n = 200).
      STATISTICAL ANALYSES: Bivariate and multiple linear regression analysis of
      associations between life-course variables and fruit and vegetable consumption.
      RESULTS: Black, Hispanic, and white respondents differed significantly in life
      course experiences, family roles, socio-demographic characteristics, and place of
      birth. Explanatory models for fruit and vegetable consumption differed among
      ethnic groups and between fruits and vegetables. Among black respondents, a
      college education was positively associated with fruit consumption; education and
      family roles contributed most to differences in fruit (R2 = .16) and vegetable
      (R2 = .09) consumption. Among Hispanic respondents, life-course experiences such
      as liking fruits and vegetables in youth, making dietary changes for health, and
      food skills were positively associated with fruit (R2 = .25) and vegetable (R2 =
      .35) consumption. Among white respondents, socio-demographic characteristics,
      such as being married with a young child or single with no child and having a
      garden as an adult, were positively associated with fruit (R2 = .20) and
      vegetable (R2 = .22) consumption. APPLICATIONS/CONCLUSIONS: An understanding of
      the determinants of food choice in different subcultural groups can be used to
      design effective nutrition interventions to increase fruit and vegetable
      consumption. Experiences such as eating fresh-picked fruits and vegetables while
      growing up or vegetable gardening as an adult may enhance fruit and vegetable
      consumption among members of some ethnic groups.

PMID- 10076583
TI  - Indicators of nutritional risk in a rural elderly Hispanic and non-Hispanic white
      population: San Luis Valley Health and Aging Study.
AB  - OBJECTIVE: To describe the prevalence of nutritional risk factors among elderly
      residents in a rural Hispanic and non-Hispanic white population. DESIGN: A
      geographically based survey of community-dwelling elderly adults.
      SUBJECTS/SETTING: From July 1993 to July 1995, all Hispanic persons older than 65
      years and an age-stratified, random sample of 69% of non-Hispanic white persons,
      from 2 Colorado counties, were invited to participate in a study of functional
      impairment and disability (81% responded). After exclusion of 184 respondents who
      required a surrogate respondent and 8 with missing diet data, the study consisted
      of 1,006 subjects. Interviews included questions similar to the Nutrition
      screening Initiative checklist, a 21-item food frequency questionnaire, and
      anthropometric measures. STATISTICAL ANALYSES PERFORMED: Gender- and ethnicity
      specific, age-adjusted prevalence for each risk factor was estimated by use of
      logistic regression. RESULTS: Hispanic participants were more likely than non
      Hispanic whites to report inadequate intake of vegetables, problems with teeth or
      dentures that limited the kinds and amounts of food eaten, difficulty preparing
      meals, and lack of money needed to buy food. Hispanic women reported nutritional
      risk factors more often than Hispanic men, although anthropometric markers
      indicated that Hispanic men may be at higher risk of nutritional deficiency.
      APPLICATIONS/CONCLUSIONS: Hispanic men and women had a higher prevalence of
      nutritional risk factors than non-Hispanic whites. Intervention programs
      targeting rural, elderly Hispanics should aim to ensure that basic nutrition
      needs (access to food, help preparing meals, and adequate dental care) are being
      met. Community programs to increase activity levels and consumption of nutrient
      dense foods are recommended.

PMID- 10076584
TI  - Evaluation of a food label nutrition intervention for women with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate an educational intervention about the food label designed
      specifically for women with type 2 diabetes mellitus. DESIGN: A pretest-posttest
      control group design. Participants received random group assignment.
      SUBJECTS/SETTING: Forty-three women aged 40 to 60 years with type 2 diabetes
      living in a rural community in Pennsylvania participated. Forty participants
      (93%) completed the program. INTERVENTION: Nine weekly group sessions were
      developed on the basis of findings from previous research among this sample.
      Principles from Ausubel's learning theory were also incorporated into program
      design and evaluation. MAIN OUTCOME MEASURES: The effectiveness of the food label
      education program on participants' knowledge was determined using a multiple
      choice test designed to measure declarative and procedural knowledge. A skills
      inventory assessed participants' perceived confidence in using the food label.
      The validity and reliability of the instruments had been established previously.
      STATISTICAL ANALYSES: Analysis of variance was performed to compare groups.
      Paired t tests compared pretest and posttest results. RESULTS: The experimental
      group showed a greater gain than the control group in total knowledge (P < .001),
      declarative knowledge (P < .001), and procedural knowledge (P < .01) at posttest.
      Posttest data showed a significant increase (P < .01) in experimental
      participants' perceived confidence in using the food label. CONCLUSIONS: Women
      with diabetes need more education about the food label. This intervention is an
      effective outpatient education program. Participant knowledge and perceived
      confidence in using the food label improved significantly as a result of the
      intervention. Future research should assess retention of knowledge gained and the
      impact of the intervention on metabolic measures of diabetes management and
      control.

PMID- 10076585
TI  - New strategies for the treatment of type 2 diabetes.
AB  - This review of current developments in the treatment of type 2 diabetes focuses
      on the achievement of normoglycemia through appropriately defined goals of diet,
      exercise, and drug therapy. Clinical nutritionists are central partners in the
      management of type 2 diabetes, and nutrition therapy is still considered the
      first-line therapy of choice. A nutritionist's role in the treatment at type 2
      diabetes is to ensure an individualized, nutritionally adequate diet for
      patients, uncomplicated by episodes of hypoglycemia. In this role, clinical
      nutritionists must be aware of potential drug interactions with diet therapy and
      may be able to provide essential feedback about possible drug interactions to
      other members of the health care team, including nurses, pharmacists, and
      physicians. The role of insulin in treating type 2 diabetes is reexamined in the
      light of newly available oral antidiabetic agents and increasing awareness of the
      importance of insulin resistance and hyperinsulinemia in the development of
      diabetes complications. Because many patients use insulin to reduce blood glucose
      and glycated hemoglobin (HbA1c) to acceptable levels, management should combine
      diet therapy with insulin and/or 1 or 2 oral antidiabetic agents to help minimize
      the dose of exogenous insulin needed for glucose control.

PMID- 10076586
TI  - Daily boron intake from the American diet.
AB  - Interest in boron as a naturally occurring trace element nutrient from the food
      supply is increasing. Mounting evidence suggests that boron is essential to human
      beings. This study explores the major food and beverage contributors of boron and
      estimates of daily boron intake from the American diet. Previous estimates in the
      literature of dietary boron consumption are based on limited foods and population
      segments. In this study we provide a more comprehensive assessment of boron
      consumption by the US population. A boron nutrient database of 1,944 individual
      foods was developed. These foods represent 95.3% by weight of all foods consumed
      in the US Department of Agriculture 1989-1991 Continuing Survey of Food Intakes
      by Individuals (1989-1991 CSFII). The Boron Nutrient Database (version 1.0) was
      then linked to the 3-day food records of 11,009 respondents to the 1989-1991
      CSFII to generate the average daily boron intake for each person. The weighted
      5th percentile, median, mean, and 95th percentile boron intakes, respectively,
      are 0.43, 1.02, 1.17 and 2.42 mg/day for men; 0.33, 0.83, 0.96 and 1.94 mg/day
      for women; and 0.40, 0.86, 1.01 and 2.18 mg/day for pregnant women. For
      vegetarian adults, these intakes are 0.46, 1.30, 1.47 and 2.74 mg/day for men and
      0.33, 1.00, 1.29 and 4.18 mg/day for women. The top 2 boron contributors, coffee
      and milk, are low in boron, yet they make up 12% of the total boron intake by
      virtue of the volume consumed. Among the top 50 boron contributors, peanut
      butter, wine, raisins, peanuts, and other nuts are high in boron. As more data
      become available on daily boron requirements, the results of this study may be
      used to assess whether Americans' daily intake of boron is adequate.

PMID- 10076587
TI  - Can ready-to-eat cereal solve common nutritional problems in child-care menus?

PMID- 10076588
TI  - Acceptability of fruit purees in peanut butter, oatmeal, and chocolate chip
      reduced-fat cookies.

PMID- 10076589
TI  - Facing the future: ADA's 1998 environmental scan.

PMID- 10076590
TI  - Medical nutrition therapy protocols: an introduction.

PMID- 10076591
TI  - Overview of gluten-sensitive enteropathy (celiac sprue)

PMID- 10076592
TI  - Infliximab (Remicade) for Crohn's disease.

PMID- 10076593
TI  - Homeopathic products.

PMID- 10076594
TI  - Rifapentine--a long-acting rifamycin for tuberculosis.

PMID- 10076595
TI  - [Seroprevalence of Central European tick-borne encephalitis in the Lorraine
      region].
AB  - BACKGROUND: Central European encephalitis, caused by the tick-borne encephalitis
      virus (TBEV), is exceptional in France. Most cases have been described in Alsace.
      As 2 cases of tick-borne encephalitis were diagnosed in the Nancy region, a
      seroepidemiological survey was conducted in the Lorraine region (Meurthe &
      Moselle, Moselle, Vosges, Meuse) in 1996. METHODS: The survey was proposed to
      approximately 1,000 persons attending preventive medicine clinics. The subjects
      were asked to fill out a self-administered questionnaire on factors related to
      tick bite exposure and underwent TBEV serology tests. RESULTS: 1,777 subjects
      participated in the survey. Half of them lived in rural areas, 91% had occasional
      or regular contact with the forest environment and 21% had experienced tick
      bites. TBEV serology (IgG) was positive in 19 subjects (1.6%; 95% CI: 0.9%-2.3%);
      9 sera were positive on Western blot (0.76). No IgM positive serum was found.
      Seroprevalence was higher in subjects with a past history of tick bites compared
      with the others (2.9% vs 1.3%, p = 0.074). CONCLUSION: The low seroprevalence of
      TBEV in this survey is not in favor of widespread tick-bite encephalitis virus in
      the Lorraine general population.

PMID- 10076596
TI  - [Non-secreting pheochromocytoma of the broad ligament revealed by appendicular
      peritonitis].
AB  - BACKGROUND: Non-secreting pheochromocytoma is an endocrine tumor located in the
      adrenal medulla in 85% of the cases. Extra-adrenal localizations account for the
      other 15%. A broad ligament localization related to an accessory adrenal gland is
      exceptional. CASE REPORT: A tumoral formation was observed during computed
      tomographic exploration of appendicular peritonitis in a 25-year-old patient. The
      tumor had developed from an ectopic adrenal gland included in the large ligament
      of the uterus. Pathology reported non-secreting pheochromocytoma confirmed by
      immunolabeling. DISCUSSION: The broad ligament localization is exceptional for
      pheochromocytomas and may mislead diagnosis. Resection is the only treatment.
      Recurrence and metastases have been reported to develop in some cases many years
      later, particularly after incomplete resection. Pathogenically, this tumor is
      remnant embryonic chromaffin tissue issuing from the parasympathetic nodes and
      developing in an ectopic adrenal gland.

PMID- 10076597
TI  - [Spinal neurenteric cyst revealed by a cauda equina syndrome].
AB  - BACKGROUND: Intraspinal neurenteric cysts are exceptional formations which
      develop from incomplete separation of the neural tube and the endodermis during
      the third week of gestation. Symptoms generally appear before the age of 40 years
      and are associated with spinal malformations. Most neurenteric cysts lie in an
      extra-spinal position in the lower cervical and upper dorsal spine. We report a
      case involving the cauda equina with no associated spinal lesion. CASE REPORT: A
      63-year-old woman was admitted for low back pain and right L3 radiculalgia
      triggered by exertion. Urinary disorders had developed over the preceding year.
      Physical examination found a spinal syndrome with hypoesthesia of the right para
      anal area, an atonic anal sphincter and a globular bladder. Plain films showed a
      widened interpedicular space between L1 and L2 interpreted as the consequence of
      an expansive intraspinal lesion. Saccoradiculography led to the diagnosis of an
      intradural lesion involving L1 and L2. At magnetic resonance imaging, the
      lesion's signal intensity was similar to cerebrospinal fluid on T1 and T2
      sequences, deforming the cauda equina and displacing the nerve roots. Surgical
      resection of the cyst was incomplete due to adherences to several roots and was
      followed by persistent radiculalgia and sphincter disorders. DISCUSSION: This
      case demonstrates an exceptional cause of cauda equina syndrome. Fissuration or
      rupture of the cyst might explain symptom exacerbation following trauma. Magnetic
      resonance imagining can confirm the cystic nature of the intradural lesion and
      help guide surgery. Resection is often incomplete with the risk of long-term
      recurrence.

PMID- 10076598
TI  - [Polymyositis in a HIV infected patient].

PMID- 10076599
TI  - [Nephropathy caused by Amanita phalloides].

PMID- 10076600
TI  - [Iatrogenic dysphagia with severe consequences: simple preventive measures].

PMID- 10076601
TI  - [What is the right hematocrit in patients with chronic renal failure?].

PMID- 10076603
TI  - [Electroconvulsive therapy].

PMID- 10076602
TI  - [Indications and modality of electorconvulsive therapy. Text of recommendations
      of the ANAES (French Society for Anesthesia and Reanimation)].

PMID- 10076604
TI  - [Pre-hospitalization reanimation in cardiac arrest].
AB  - THE SURVIVAL CHAIN: The delay to restoration of spontaneous circulation is the
      key to prognosis of cardiac arrest occurring outside the hospital. Among the many
      etiologies of cardiac arrest, sudden onset ventricular fibrillation is the number
      one cause of sudden death in adults. Better prognosis depends on effective
      organisation founded on the concept of a "survival chain". ALERT AND
      RESUSCITATION: By alerting the emergency units and performing the basic gestures
      of cardiopulmonary resuscitation (freeing the airways, mouth-to-mouth ventilation
      and closed chest cardiac massage) those witnessing the event take the first steps
      in the survival chain while waiting for the paramedical and medical teams to
      arrive. DEFIBRILLATION: In case of ventricular fibrillation, prognosis is
      directly related to the delay to defibrillation. Defibrillators used by specially
      trained paramedics before a physician arrives on the scene have considerably
      improved prognosis. SPECIALIZED RESUSCITATION: Precise algorithms help guide
      treatment in accordance with the observed cardiac rhythm. Tracheal intubation and
      artificial ventilation are fundamental. Among the useful drugs, epinephrine is by
      far the most important for improving myocardial and cerebral perfusion, improving
      the chances of recovering spontaneous circulation. The only anti-arrhythmic drug
      currently used is lidocaine. Infusion of alkaline fluid is only useful in
      specific cases of prolonged resuscitation. Expired CO2 monitoring may be a useful
      guide, but discontinuing resuscitation is strictly a medical decision. AFTER
      RESUSCITATION: When spontaneous circulation has been achieved, the patient must
      be transported to a cardiac hospital for specialized care and etiological
      treatment.

PMID- 10076605
TI  - [Biologic rhythms: their changes in night-shift workers].
AB  - ENVIRONMENTAL STRESS: Environmental cycles, such as the light-dark cycle, provide
      information used by the biological clock in the hypothalamus to synchronize the
      biological systems and maintain the organism's internal cohesion. In persons
      whose work schedules include night hours (approximately 20% of the working
      population in France) the sleep-wake cycles are not in phase with these
      environmental cycles. BIOLOGICAL RHYTHMS: What effect does the conflicting
      information perceived by night-shift workers have on their biological rhythms?
      Indices of the processes going on in the cerebral clock, these biological rhythms
      are the only tool available in man to determine possible dysfunction of the
      clock. Several studies have identified these rhythms in night-shift workers but
      results have been contradictory. PARTIAL ADAPTATION: Recently we made repeated
      measurements every 10 min over a 24 hour period in night-shift workers to
      determine the precise melatonin, cortisol, and thyrotropin (TSH) patterns, which
      reflect the endogenous clock, and prolactin (PRL) and growth hormone (GH)
      patterns which are influenced by sleep but also have a circadian component. This
      study demonstrated that there is some, but partial, adaptation of the biological
      rhythms in these persons. The shift in the melatonin pattern is quite variable
      from one individual to another. Night work causes a distortion in the cortisol
      and TSH rhythms. This partial adaptation is also seen in the GH and PRL curves,
      mainly related to sleep, but whose endogenous component previously described in
      other experimental situations is found in night workers with a distribution
      incompletely adapted to the secretory episodes. RESEARCH PERSPECTIVES: Both
      daytime sleep and night-time work are associated with perturbed endocrine
      functions which could explain certain health problems and sleep disorders
      observed (or avowed) after several years of night-shift work. These problems
      require further research into factors susceptible of resynchronizing the
      biological clock.

PMID- 10076606
TI  - [Hepatic and mediastinal hydatid cyst caused by eosinophilic pleural effusion].

PMID- 10076607
TI  - Surgical implications of therapeutic angiogenesis.

PMID- 10076608
TI  - Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy.
AB  - BACKGROUND: Reports of better results at national referral centers than at low
      volume community hospitals have prompted calls for regionalizing
      pancreaticoduodenectomy (the Whipple procedure). We examined the relationship
      between hospital volume and mortality with this procedure across all US
      hospitals. METHODS: Using information from the Medicare claims database, we
      performed a national cohort study of 7229 Medicare patients more than 65 years
      old undergoing pancreaticoduodenectomy between 1992 and 1995. We divided the
      study population into approximate quartiles according to the hospital's average
      annual volume of pancreaticoduodenectomies in Medicare patients: very low (<
      1/y), low (1-2/y), medium (2-5/y), and high (5+/y). Using multivariate logistic
      regression to account for potentially confounding patient characteristics, we
      examined the association between institutional volume and in-hospital mortality,
      our primary outcome measure. RESULTS: More than 50% of Medicare patients a
      undergoing pancreaticoduodenectomy received care at hospitals performing fewer
      than 2 such procedures per year. In-hospital mortality rates at these low- and
      very-low-volume hospitals were 3- to 4-fold higher than at high-volume hospitals
      (12% and 16%, respectively, vs 4%, P < .001). Within the high-volume quartile,
      the 10 hospitals with the nation's highest volumes had lower mortality rates than
      the remaining high-volume centers (2.1% vs 6.2%, P < .01). The strong association
      between institutional volume and mortality could not be attributed to patient
      case-mix differences or referral bias. CONCLUSIONS: Although volume-outcome
      relationships have been reported for many complex surgical procedures, hospital
      experience is particularly important with pancreaticoduodenectomy. Patients
      considering this procedure should be given the option of care at a high-volume
      referral center.

PMID- 10076609
TI  - Adjuvant immunotherapy using fibroblasts genetically engineered to secrete
      interleukin 12 prevents recurrence after surgical resection of established tumors
      in a murine adenocarcinoma model.
AB  - BACKGROUND: To explore effective therapeutic strategy against cancer of the
      gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin
      12 (IL-12) was developed as an adjuvant therapy against murine tumor after
      surgical resection. METHODS: Initially, IL-12 was genetically engineered into
      fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro
      antitumor effects. In the vaccination model, irradiated C-26 tumor mass was
      reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to
      examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells
      producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent
      potent tumor suppression when coinoculated with C-26 cells in vivo. Specific
      immunity was also acquired in 63% of mice in vivo. In the vaccination model,
      protective immunity was developed in 70% of mice that were inoculated with
      irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not
      observed in vaccinated mice, although 44% of control mice had recurrence.
      CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12
      with irradiated tumor mass was proved to be an effective tumor vaccine. This
      system of vaccination is easily applicable to clinical situations, particularly
      to human gastrointestinal tract cancers.

PMID- 10076610
TI  - Innovative techniques for and results of portal vein reconstruction in living
      related liver transplantation.
AB  - BACKGROUND: Portal vein reconstruction is a crucial factor affecting the outcome
      of a successful living-related liver transplantation. We describe here our
      experience with portal vein reconstruction in 314 cases of living-related liver
      transplantation with use of novel surgical modalities to enable the transplant
      surgeons to deal with any size mismatch between the donor's and recipient's
      portal veins. METHODS: Portal vein reconstruction was classified into 2 major
      groups, anastomosis without and with a vein graft. When there was no stenosis of
      the recipient portal vein and the diameter was the same, the portal trunk was
      used for anastomosis. When the diameter mismatch was minimal, branch patch
      anastomosis was feasible. When the recipient portal vein was significantly
      stenotic and the portal vein of the graft was long enough, we removed the
      stenotic trunk and constructed an anastomosis between the graft portal vein and
      the confluence of the recipient portal vein. When the graft portal vein was
      short, a vein graft was interposed. The vein patch technique was preferable when
      the diameter of the graft vein was not large enough for the interposition
      technique. RESULTS: Anastomosis without vein graft included trunk anastomosis (n
      = 156), branch patch anastomosis (n = 39), and confluence anastomosis (n = 22).
      Anastomosis with vein graft used the interposition technique (n = 77) and vein
      patch technique (n = 27). The origin of the grafts was mostly from the maternal
      left ovarian vein (70%) or the paternal inferior mesenteric vein (27%).
      Complications related to portal vein reconstruction occurred in 16 (5%) patients:
      portal vein thrombosis in 8, stenosis in 7, and fatal rupture in 1 patient. The
      incidence of complications was similar for all techniques except for confluence
      anastomosis. CONCLUSION: Our innovative techniques should be helpful for
      overcoming diameter or length mismatches in portal vein reconstruction in
      pediatric liver transplantation.

PMID- 10076611
TI  - Carotid endarterectomy with patch closure versus carotid eversion endarterectomy
      and reimplantation: a prospective randomized study.
AB  - BACKGROUND: Although carotid eversion endarterectomy (CEE) has obtained consensus
      providing excellent early and late results, conventional carotid endarterectomy
      (CEA) with or without patching continues to be considered the gold standard
      surgical procedure. The few studies published to date comparing CEE with CEA in a
      small series of patients have failed to show substantial advantages of one
      technique over the other, and further randomized comparative studies are still
      required. The purpose of this study was to compare the outcome of CEA with
      routine patch closure (CEAP) with that of CEE and reimplantation (CEER) of the
      internal carotid artery in the common carotid artery. METHODS: Three hundred
      thirty-six primary CEAs performed in 310 patients were randomized into 2 groups,
      167 CEAPs and 169 CEERs. Surviving patients underwent duplex ultrasound scan
      control at 30 days, 6 months, 12 months, and every postoperative year thereafter.
      The mean follow-up was 34 months (range, 1 to 69 months). Demographic
      characteristics, risk factors, associated diseases, and indications for surgery
      were comparable in the 2 groups. RESULTS: Although the rate of intraoperative
      electroencephalogram changes was comparable in the 2 groups, the incidence of
      shunting was statistically higher in the CEAP group (28.1% vs 1.2%, P < .00001).
      The carotid cross-clamping time was significantly lower in the CEER group (P =
      .01). Although all deaths were in the CEAP group, the overall perioperative death
      and stroke-related death rates were comparable in the 2 groups. The perioperative
      stroke rate was statistically higher in the CEAP group (2.9% vs 0%, P = .03).
      Although the recurrent stenosis rate was comparable in the 2 groups (1.2% vs 0%),
      the CEAP group had a statistically higher rate of combined recurrent stenoses and
      occlusions (4.9% vs 0%, P = .003). The late mortality rate was similar in both
      groups. CONCLUSIONS: Although the outcome of CEAP in this series is consistent
      with that of the main reported trials, the CEER procedure is less likely than
      CEAP to cause perioperative stroke and death and seems superior in reducing the
      incidence of recurrent stenosis and late occlusive events.

PMID- 10076612
TI  - C1-esterase inhibitor and its effects on endotoxin-induced leukocyte adherence
      and plasma extravasation in postcapillary venules.
AB  - BACKGROUND: C1-esterase inhibitor (C1-INH) has been shown to have beneficial
      effects in patients with sepsis. However, the microcirculatory effects of C1-INH
      during sepsis are unknown. This study investigated the influence of C1-INH on
      leukocyte-endothelial cell adhesion, vascular leakage, and venular
      microhemodynamics in postcapillary venules of rat mesentery during endotoxemia.
      METHODS: Thirty-two anesthetized Wistar rats randomly received 1 of 4 treatments:
      pretreatment with infusion of C1-INH in a concentration of 7.5 U.kg-1 body weight
      (C1-INH-7.5 group, n = 8) or in a concentration of 15 U.kg-1 body weight (C1-INH
      15 group, n = 8) followed by continuous infusion of Escherichia coli
      lipopolysaccharide (LPS). The LPS group (n = 8) was pretreated with saline
      solution 30 minutes before LPS infusion. The control group (n = 8) received
      equivalent amounts of saline infusion. Leukocyte adherence, red blood cell
      velocity, and vessel diameters in postcapillary venules of rat mesentery were
      determined every 60 minutes during a period of 120 minutes using in vivo
      videomicroscopy. Vascular permeability was determined by measuring the
      extravasation of fluorescence-labeled albumin. Venular wall shear rate was
      calculated from mean red blood cell velocity and vessel diameter. RESULTS: LPS
      infusion induced a decrease in venular wall shear rate and an increase in
      leukocyte adherence and vascular permeability in postcapillary venules of rat
      mesentery. All microcirculatory disturbances were attenuated by pretreatment with
      C1-INH, showing no significant difference between the 2 concentrations.
      CONCLUSIONS: Pretreatment with C1-INH attenuates endotoxin-induced leukocyte
      adherence and macromolecular leakage in postcapillary venules of rat mesentery,
      indicating that complement inhibition might be a therapeutic tool in the
      treatment of sepsis.

PMID- 10076613
TI  - Rapid diagnostic imaging of acute, nonclassic appendicitis by leukoscintigraphy
      with sulesomab, a technetium 99m-labeled antigranulocyte antibody Fab' fragment.
      LeukoScan Appendicitis Clinical Trial Group.
AB  - BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of
      a technetium 99m-labeled antigranulocyte antibody Fab' fragment (sulesomab) as a
      diagnostic imaging agent in patients with suspected acute, nonclassic
      appendicitis. METHODS: This prospective multicenter trial involved 141 children
      and adults with suspected acute, nonclassic appendicitis. The investigators
      interpreted planar images acquired 15 to 30 minutes and 1, 2, and 4 hours after
      injection and also by single-photon emission computed tomography (SPECT). The
      imaging results were confirmed surgically, whereas nonsurgical patients were
      considered as not having appendicitis (intent to treat). RESULTS: Sulesomab had a
      sensitivity of 91% (29/32 patients) and a negative predictive rate of 97% for
      acute appendicitis. It detected additional abnormalities in 7 of 9 patients with
      other inflammatory abdominal disease and had a specificity of 92% (91/99
      patients) and a positive predictive value of 80% for surgically confirmed right
      lower-quadrant disease. In positive studies, 26% were identified by planar
      imaging at 15 to 30 minutes, 46% by 1 hour, 63% by 2 hours, and 71% by 4 hours;
      29% required SPECT to detect the abnormality. Scanning time was 5 to 10 minutes
      per planar image and about 45 minutes for a SPECT study. Investigators found that
      sulesomab would have changed clinical management or reduced additional diagnostic
      studies in 64% of the patients. Adverse events were infrequent, minor, and self
      limiting (9/141 patients, 6%). No human antimurine antibody response occurred in
      48 evaluable patients. CONCLUSIONS: Sulesomab is safe, well-tolerated, and with
      no apparent immunogenicity. Focal inflammation or infection in the setting of
      suspected atypical appendicitis is rapidly and accurately detected. Management
      decisions incorporating sulesomab imaging potentially provide clear patient
      benefits, especially by correctly predicting surgery to be unnecessary in 97% of
      patients without acute appendicitis.

PMID- 10076614
TI  - Radioisotope evaluation of the esophageal remnant and the gastric conduit after
      gastric pull-up esophagectomy.
AB  - BACKGROUND: The act of swallowing after gastric pull-up esophagectomy has not
      been thoroughly investigated. The aim of this study was to evaluate deglutition
      in the esophageal remnant and in the gastric conduit in patients who have
      undergone this operation. METHODS: The residual radionuclide activity was
      measured 15 seconds after a swallow in the esophageal remnant and at intervals up
      to a maximum of 120 minutes after a swallow in the gastric conduit. The
      scintigraphic rate of transit of a bolus in both areas was compared in patients
      who had anastomosis in the neck (n = 15) versus patients who had anastomosis in
      the chest (n = 19). Comparisons were also made between patients with and without
      symptoms of dysphagia. The scintigraphic measurements were also correlated with
      anastomotic diameters, measured with use of a volumetric balloon insufflation
      method, at 3, 6, and 12 months after operation. RESULTS: There were no
      significant differences in esophageal residual radionuclide activity at 15
      seconds after a swallow in the groups with anastomosis in the neck versus
      anastomosis in the chest, with 30% residual activity up to 12 months after
      operation in both groups (P = .24). In the patients as a whole the 50% gastric
      conduit emptying time of 44 to 61 minutes did not change during the first
      postoperative year (P = .12). There was no association between anastomotic
      diameter and residual activity in the remaining esophagus (P < .126). Moderate
      and severe dysphagia was reported in only a few patients, and there was no
      correlation between dysphagic symptoms and retention in the residual esophagus or
      slower emptying in the gastric conduit. CONCLUSIONS: The amount of peristaltic
      activity in the remaining esophagus after esophagectomy with gastric replacement
      is unaffected by the level of the anastomosis. The gastric conduit empties slowly
      in all patients, and there is no correlation between the rate of emptying and
      either anastomotic diameter or symptoms of dysphagia.

PMID- 10076615
TI  - The serum interleukin 8 level reflects hepatic mitochondrial redox state in
      hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass.
AB  - BACKGROUND: We have recently developed a simple method of hyperthermochemohypoxic
      isolated liver perfusion (HILP) as a regional therapy for unrecognized liver
      micrometastases. However, little is known about the influence of HILP on cytokine
      production and liver function. We investigated the influence of HILP on
      interleukin 8 (IL-8) production and the hepatic mitochondrial function and
      assessed the relationship between these 2 parameters. We also measured the serum
      tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels
      to examine the involvement of HILP-induced cytokines in the tumor response.
      METHODS: Sixteen patients with metastatic liver tumors were randomly assigned to
      undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n =
      7). The isolated liver was perfused for 30 minutes with Ringer's lactate solution
      containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without
      oxygenation. RESULTS: The serum IL-8 levels in group A were markedly increased,
      with peaks at 3 hours after reperfusion, which was significantly higher than
      levels in group B (P < .01). In group A the arterial ketone body ratio, which
      reflects the hepatic mitochondrial redox state, decreased during perfusion and
      was gradually restored to the preperfusion level 1 hour after reperfusion.
      However, in group B it decreased during hepatectomy but rapidly recovered 5
      minutes after hepatectomy. There was a significant negative correlation between
      the peak serum IL-8 level and the initial velocity of arterial ketone body ratio
      recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The
      serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients
      in group A. CONCLUSIONS: We have shown that HILP resulted in augmented IL-8
      release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects
      the hepatic mitochondrial redox state. These findings suggest that IL-8
      production may be associated with hepatic mitochondrial impairment during
      ischemia. This work may contribute to new therapeutic strategies not only for
      hepatic ischemia reperfusion injury but also for metastatic liver tumors.

PMID- 10076616
TI  - Inguinal hernia repair in patients with coagulation problems: prevention of
      postoperative bleeding with human fibrin glue.
AB  - BACKGROUND: Our purpose was to establish the efficacy of human fibrin glue (HFG)
      in preventing coagulative complications after inguinal hernia repair in patients
      with coagulation disorders. METHODS: A randomized controlled trial of 50 patients
      with coagulation disorders undergoing hernia repair was performed. Patients had
      concurrent coagulopathies as a consequence of liver disease or long-term
      treatment with anticoagulants. Coagulopathies were defined according to the
      following criteria: prothrombin time < 10.5 seconds, activated partial
      thromboplastin time < 21 seconds, and fibrinogen < 230 mg/dL. Patients were
      randomized in a 1:1 ratio with (group A) or without (control group B) use of HFG.
      RESULTS: Postoperative hemorrhagic complications were significantly reduced in
      group A (4%) compared with group B (24%). CONCLUSION: This study shows that HFG
      is effective in preventing local hemorrhagic complications after herniorrhaphy in
      patients with concurrent coagulation disorders. This implies that the use of HFG
      reduces the costs of prolonged hospitalization related to such complications.

PMID- 10076617
TI  - The combined impact of donor age and acute rejection on long-term cadaver renal
      allograft survival.
AB  - BACKGROUND: Acute rejection (AR) is an important risk factor for long-term renal
      graft loss. Furthermore, donor age is also associated with graft outcome. We
      analyzed the combined effects of cadaver donor age and AR on long-term graft
      survival. METHODS: A retrospective review was made of 112 cadaver renal
      transplants at a single center. Only grafts functioning at least 3 months were
      included in this analysis. RESULTS: The 3-year survival of AR-free grafts was
      superior to that of grafts with AR (98% vs 67%, P < .001). Within the AR cohort
      donor age > 50 years (P < .05) had an additional negative impact on graft
      survival. The 3-year survival of an older donor graft with AR was 33% versus 82%
      for a younger donor graft with AR. CONCLUSIONS: AR was a significant predictor of
      long-term graft loss. Older donor kidneys with AR had poorer graft survival than
      did younger donor kidneys with AR.

PMID- 10076618
TI  - A prospective pilot study of extended (D3) and superextended para-aortic
      lymphadenectomy (D4) in patients with T3 or T4 gastric cancer managed by total
      gastrectomy.
AB  - BACKGROUND: Japanese surgeons have been actively performing extended
      lymphadenectomy (D2, removal of perigastric nodes and nodes along the left
      gastric, common hepatic, celiac and splenic arteries; or D3, D2 plus removal of
      nodes in the hepatoduodenal ligament, in the retropancreatic space and along the
      vessels of the transverse mesocolon). In recent years interest has expanded to
      superextended lymphadenectomy (D4) of nodes around abdominal aorta (para-aortic
      lymph nodes from aortic hiatus to aortic bifurcation). Because the therapeutic
      value of this D4 procedure remains controversial, we initiated a prospective
      study to compare D3 and D4 lymphadenectomy. METHODS: Seventy patients with T3 or
      T4 gastric cancer and without macroscopic metastasis to the para-aortic nodes
      treated by potentially curative total gastrectomy were randomized to D4 (group A,
      n = 35) and D3 (group B, n = 35) lymphadenectomies. RESULTS: Metastases to para
      aortic nodes were found in 4 patients. Postoperative survival after D4 resection
      was not statistically significant between the groups. Postoperative morbidity for
      group A was greater. In group A 4 patients had postoperative retention of intra
      abdominal fluid (lymphorrhea) and 4 others had prolonged diarrhea. One patient in
      each group died of postoperative complications. CONCLUSIONS: Surgical treatment
      of microscopic disease in grossly normal para-aortic lymph nodes may generate
      occasional long-term survivors. Selecting appropriate candidates who might
      benefit from D4 resections needs to be refined. On the basis of this study, a
      nationwide study should be considered.

PMID- 10076619
TI  - Liver resection for hepatocellular carcinoma in octogenarians.
AB  - BACKGROUND: Liver resection is risky in patients aged > or = 80 years. Because of
      short life expectancies and improved nonoperative modalities, the role of liver
      resection in octogenarians with hepatocellular carcinoma (HCC) is unclear.
      METHODS: A retrospective review of the operative results of 260 patients with HCC
      between 1991 and 1997 was performed. According to the age at the time of
      operation, these patients were divided into 2 groups. Group 1 comprised 21
      patients aged > or = 80 years, and group 2 comprised the other 239 younger
      patients. The backgrounds, pathologic features of the tumor, and operative
      results of the patients were compared. RESULTS: Octogenarians had a higher
      incidence of associated medical diseases, a higher incidence of negative serum
      hepatitis B surface antigen, a lower alpha-fetoprotein level, and a higher
      indocyanine green retention rate. Although octogenarians had a longer
      postoperative hospital stay, there were no significant differences between the 2
      groups regarding operative morbidity and mortality. The 5-year disease-free and
      actuarial survival rates for octogenarians and younger patients were 50.6% and
      35.3% (P = .15) and 40.9% and 59.3% (P = .46), respectively. CONCLUSION: Under
      meticulous preoperative assessments and postoperative care, liver resection for
      HCC is justified in selected octogenarians, with short- and long-term results
      comparable to those of younger patients.

PMID- 10076620
TI  - Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide
      synthase and intestinal transit.
AB  - BACKGROUND: The disrupted intestinal transit during endotoxemia may be mediated
      by nitric oxide (NO). We hypothesized that the isoforms of nitric oxide synthase
      (NOS) are up-regulated in intestinal smooth muscle during endotoxemia and that
      the scavenging of NO will normalize transit. METHODS: Rats were given Escherichia
      coli lipopolysaccharide (LPS) 10 mg/kg intravenously and were killed 4 hours
      later. To determine the activity of NOS isoforms in the jejunum and ileum, the
      conversion of tritiated L-arginine to tritiated L-citrulline was measured.
      Western immunoblots were performed by incubating the extracted protein with
      specific polyclonal antibodies. To determine intestinal transit, rats were
      divided into 4 groups: 0.9% sodium chloride 1 mL/h intravenously for 5 hours, LPS
      10 mg/kg intravenous bolus plus 1 mL/h 0.9% sodium chloride intravenously, LPS
      plus oxyhemoglobin 0.5 g/kg/h intravenously, and oxyhemoglobin 0.5 g/kg/h
      intravenously. RESULTS: LPS increased the constitutive and inducible NOS enzyme
      activities in the jejunum and ileum. Western blots demonstrated that LPS up
      regulates both the NOS1 and NOS2 isoforms in jejunal and ileal smooth muscle.
      Oxyhemoglobin alone increased intestinal transit compared with controls, whereas
      endotoxemia increased intestinal transit, which was ameliorated with infusions of
      oxyhemoglobin. CONCLUSIONS: NO may play a major role in mediating the rapid
      intestinal transit induced by endotoxemia.

PMID- 10076621
TI  - Lessons from a life in surgery. I. Do you want the high figure or the low?

PMID- 10076622
TI  - Rudolf Nissen: the man behind the fundoplication.

PMID- 10076623
TI  - Coloenteric fistula from chicken-bone perforation of the sigmoid colon.

PMID- 10076624
TI  - Total posterior tracheal wall resection and reconstruction with
      pharyngolaryngoesophagectomy.
AB  - BACKGROUND: Extensive posterior tracheal wall invasion in pharyngoesophageal
      carcinomas is considered by many authors to be a contraindication for total
      pharyngolaryngoesophagectomy and gastric transposition (TPLEGT). The purpose of
      this report is to challenge this concept and to illustrate posterior tracheal
      wall resection in selected cases followed by reconstruction of the trachea by
      anastomosis of the remnant trachea to the anterior gastric wall without
      thoracotomy. PATIENTS AND METHODS: Four of 36 consecutive patients (11%)
      undergoing TPLEGT were treated with the following procedure: 3 patients had
      cervical esophageal carcinomas and 1 had a postcricoid carcinoma. All the
      patients had longitudinal involvement of the posterior wall of the trachea, which
      necessitated resection within 1.5 to 2.0 cm of the carina. The technique
      consisted of removing the specimen en bloc with the posterior wall of the
      trachea. Without the specimen in place, the surgical field at the thoracic inlet
      was large enough to permit a continuous running suture between the remnant
      tracheal wall and the serosa of the transposed stomach. The pharyngogastric
      anastomosis was subsequent to this procedure. RESULTS: One patient died in the
      hospital after complications of chylothorax and sepsis, but this was unrelated to
      the gastrotracheal anastomosis. One patient died of pneumonia after a
      cerebrovascular accident 2 months after the procedure. Two patients had effective
      palliation for 9 and 18 months, respectively. CONCLUSION: TPLEGT may be used in
      selected patients with pharyngoesophageal tumors. The anterior wall of the
      stomach is a suitable substitute for the posterior tracheal wall. The gastric
      bulging into the trachea is not enough to obstruct the lumen. However, we caution
      that tracheal involvement should be limited to the midline and that there is a
      potential for a gastrotracheal fistula.

PMID- 10076625
TI  - Membrane inlet ion trap mass spectrometry for the direct measurement of dissolved
      gases in ecological samples.
AB  - The use of an ion trap mass spectrometer with three different membrane inlet
      probes is described. Two methods of removing water from the sample are compared.
      One is the use of a PTFE-silicone rubber double membrane, PTFE is relatively
      impermeable to water and so reduces the amount entering with the gas sample
      (Probe A). The second is the use of a silicone rubber membrane covered long
      probe, which condenses water out of the sample (Probe B). Response times (100%)
      for dissolved N2O, O2, Ar and CO2 without He in the chamber vary from between 158
      and 684 s with Probe A. For the same probe with He, the response times were
      between 283 and 551 s. In the gas phase response times were between 99 and 153 s
      with He and 117 and 122 s without He. Probe B had 100% response of between 122
      and 152 s for dissolved gases. Further extension of the probe by 2 m slowed
      response times as did increasing the ionisation time. Response times for Probe B
      increased to between 99 and 340 s when ionisation time increased from 1000 to
      24,930 microseconds. Plots of output against concentration showed the steepest
      line of response for the short single membrane covered probe with 1000
      microseconds ionisation time. Increasing the ionisation time, extending the probe
      and the use of a double membrane all reduced the gradient of output against
      concentration for every gas tested. In an intact sediment core, concentrations of
      O2, N2O and CO2 rose at the start and the concentration of N2 fell. As the
      disturbed sediment settled, this was reversed. The initial increase in O2
      concentration stimulated respiration and inhibited the final pathway in
      dentrification producing higher concentrations of N2O and reducing the
      concentration of N2.

PMID- 10076626
TI  - Method for purification of bacterial endospores from soils: UV resistance of
      natural Sonoran desert soil populations of Bacillus spp. with reference to B.
      subtilis strain 168.
AB  - Endospores of Bacillus spp. were purified from three Sonoran desert soil samples
      by Chelex extraction and NaBr density gradient centrifugation and their UV
      resistances compared with that of B. subtilis strain 168. Natural spore
      populations exhibited tight adherence to soil particles which was not readily
      overcome by the extraction and purification procedure. It was observed that
      spores purified from soil exhibited 2-3 fold higher resistance to UV (as measured
      by the 90% lethal dose, LD90) than did B. subtilis strain 168 grown on NSM, a
      standard laboratory sporulation medium, and purified by the same extraction
      procedure. Cultivation of spore-forming bacteria isolated from soil on NSM
      resulted in production of spores with essentially identical UV resistance as
      strain 168, suggesting that spore UV resistance is influenced by the environment
      in which spores are produced.

PMID- 10076627
TI  - Identification of Leptospira biflexa by real-time homogeneous detection of rapid
      cycle PCR product.
AB  - Sequence analysis of 16S rRNA genes extracted from nucleic acids databases
      enabled the identification of a Leptospira biflexa (L. biflexa) signature
      sequence, against which a reverse primer designated L613, was designed. This
      primer, when used in conjunction with a universal bacterial specific forward
      primer designated Fd1, enabled the development of a LightCycler-based PCR
      protocol in which fluorescence emission due to binding of SYBR Green I dye to
      amplified products could be detected and monitored. A melting temperature (Tm),
      determined from the melting curve of the amplified product immediately following
      the termination of thermal cycling, confirmed that the product was that of L.
      biflexa. Agarose gel electrophoresis therefore was not necessary for
      identification of PCR products. The PCR protocol was very rapid, and consisted of
      30 cycles with a duration of 20 s for each cycle with the monitoring of the
      melting curve requiring an additional 3 min. The whole protocol was completed in
      less than 20 min. The PCR protocol was also specific and enabled the
      identification of 18 strains of L. biflexa, whilst excluding 14 strains of L.
      interrogans and Leptonema illini. Two examples of its utility in improving work
      flow of a Leptospira reference laboratory are presented in this article. The use
      of a simple boiling method for extraction of DNA from all the members of the
      Leptospiraceae family DNA further simplifies the procedure and makes its use
      conducive to diagnostic laboratories.

PMID- 10076628
TI  - Clinical correlation of a skin antisepsis model.
AB  - The use of pigskin as a test substrate for evaluating topical antimicrobial
      activity has been developed. Simulated handwashing protocols with this in vitro
      model in parallel with in vivo studies have been evaluated, based on an ASTM
      method for the clinical evaluation of a healthcare personnel handwash. Using
      Serratia marcescens as the test organism, similar log reductions were observed
      using the in vitro model when compared to in vivo efficacy. Results suggest that
      this model can be used as a reliable indicator of antiseptic efficacy on the
      skin. The use of sterilized skin simplifies the use of this model for both
      efficacy and skin-pathogen interaction studies.

PMID- 10076629
TI  - Impedance microbiology: quantification of bacterial content in milk by means of
      capacitance growth curves.
AB  - The impedancimetric method is a technique for the rapid evaluation of milk
      bacterial content and also of its subproducts. Several authors have made use of
      culture conductance changes during bacterial growth for quantitative and
      qualitative assessments of microbial growth. However, interface capacitance
      curves, Ci, have not been used. In this paper, we quantify bacteria in cow raw
      milk by following their growth as the above-mentioned capacitance change time
      course event. With it, bigger growth variations, shorter detection times and a
      better coefficient of correlation with the plate count method were obtained than
      those yielded by conductance curves. Calibration was performed by plotting
      initial known concentrations, IC (CFU/ml), as a function of the time detection
      theshold (TDT).

PMID- 10076630
TI  - Evaluation of methodologies including immunofluorescent assay (IFA) and the
      polymerase chain reaction (PCR) for detection of human pathogenic microsporidia
      in water.
AB  - Microsporidia is a term used to describe a group of emerging protozoan pathogens
      whose environmental occurrence has only recently been documented due to lack of
      detection methodologies. This study evaluates and describes current methods for
      detection of microsporidia in water. Standard methods, for the collection and
      processing of large volumes of water to detect protozoa, showed only a 4.8%
      recovery, of microsporidia spores, from 100 l volumes of tap. Immunofluorescent
      assay (IFA) analysis was assessed using two different antibodies specific for
      human pathogenic microsporidia. Results indicated that the use of IFA for routine
      screening of water for microsporidia was not an acceptable approach. The
      antibodies tested for the IFA resulted in false positives and false negatives and
      did not react with Enterocytozoon bieneusi, which is an important human
      pathogenic microsporidia. Finally, the small sizes of the human pathogenic
      microsporidia prevent confirmation and species determination by light microscopic
      methods. Two methods for isolating microsporidia DNA from water for use in
      polymerase chain reaction (PCR) amplification of microsporidia target sequences
      were assessed. Both of these DNA isolation methods when combined with the PCR
      showed the ability to detect less than ten spores in purified water concentrates.
      Thus, this study represents the first documentation and evaluation of current
      methods for the detection of human pathogenic microsporidia in water.

PMID- 10076631
TI  - Analysis of the structural diversity of mycolic acids of Rhodococcus and Gordonia
      [correction of Gordonla] isolates from activated sludge foams by selective ion
      monitoring gas chromatography-mass spectrometry (SIM GC-MS)
AB  - A method using Selective Ion Monitoring (SIM) gas chromatography-mass
      spectrometry is described for analysis of mycolic acids which reveals a hitherto
      unrecognised chemical structural diversity among these in some members of the
      Mycolata. The structural interpretation of mass spectral data of mycolic acids
      from Rhodococcus spp and Gordonia [corrected] spp using SIM is discussed.

PMID- 10076632
TI  - Three sample preparation protocols for polymerase chain reaction based detection
      of Cryptosporidium parvum in environmental samples.
AB  - Cryptosporidium parvum is a protozoan parasite responsible for an increasing
      number of outbreaks of gastrointestinal illness worldwide. In this report, we
      describe development of sample preparation protocols for polymerase chain
      reaction (PCR)-based detection of C. parvum in fecal material and environmental
      water samples. Two of these methods were found adequate for isolation of
      Cryptosporidium DNA from filtered water pellet suspensions. The first involved
      several filtration steps, immunomagnetic separation and freeze-thaw cycles. The
      second method involved filtration, addition of EnviroAmp lysis reagent, freeze
      thaw cycles and precipitation of the DNA with isopropanol. Using nested PCR, we
      detected 100 oocysts/ml of filtered water pellet suspension, with either of the
      above sample preparation procedures. Nested PCR increased sensitivity of the
      assay by two to three orders of magnitude as compared to the primary PCR. The
      detection limit for seeded fecal samples was 10-fold higher than for filtered
      environmental water pellet suspension. Nested PCR results showed 62.4 and 91.1%
      correlation with immunofluorescence assay (IFA) for fecal samples and filtered
      environmental water pellet suspensions, respectively. This correlation decreased
      to 47.2% and 44.4%, respectively, when only IFA positive samples were analyzed.
      However, in fecal samples contaminated with a high number (> 10(5)/g) of C.
      parvum oocysts, this correlation was 100%.

PMID- 10076633
TI  - Influence of residual uracil-DNA glycosylase activity on the electrophoretic
      migration of dUTP-containing PCR products.
AB  - In diagnostic amplification protocols contamination by previously amplified
      nucleic acids is considered the major source of false positive results.
      Substituting dUTP for dTTP in the PCR and initial treatment with uracil-DNA
      glycosylase (UNG) virtually eliminates these carryover contaminations. Subsequent
      procedures to visualize the amplicons or to optimize sensitivity and specificity
      of the test are not always fully compatible with UNG-treated PCR products. Here
      we describe the more pronounced influence of residual UNG activity on the
      migration of PCR amplification products in polyacrylamide as compared to agarose
      gels.

PMID- 10076634
TI  - A PCR-based strategy for simple and rapid identification of rough presumptive
      Salmonella isolates.
AB  - The purpose of the present study was to investigate the application of ready-to
      go Salmonella PCR tests, based on dry chemistry, for final identification of
      rough presumptive Salmonella isolates. The results were compared with two
      different biotyping methods performed at two different laboratories. The
      sensitivity of the BAX Salmonella PCR test was assessed by testing a total of 80
      Salmonella isolates, covering most serogroups, which correctly identified all the
      Salmonella strains by resulting in one 800-bp band in the sample tubes. The
      specificity of the PCR was assessed using 20 non-Salmonella strains, which did
      not result in any DNA band. A total of 32 out of the 36 rough presumptive
      isolates were positive in the PCR. All but one isolate were also identified as
      Salmonella by the two biochemical methods. All 80 Salmonella strains were also
      tested in the two multiplex serogroup tests based on PCR beads. All strains
      belonging to the serogroups B, C1, C2-C3, and D were grouped correctly. Among the
      32 rough presumptive isolates identified, 19 isolates resulted in a band of 882
      bp (serogroup B), 11 isolates resulted in a band of 471 bp (serogroup C1), and
      two isolates showed a band of 720 bp (serogroup D). In conclusion, rough
      presumptive Salmonella isolates can be conveniently confirmed to the serogroup
      level, using the pre-mixed PCR tests. The system can be easily implemented in
      accredited laboratories with limited experience in molecular biology.

PMID- 10076635
TI  - Bi-functional gfp- and gusA-containing mini-Tn5 transposon derivatives for
      combined gene expression and bacterial localization studies.
AB  - The gfp gene, encoding the green fluorescent protein, was combined with the gusA
      gene, coding for the beta-glucuronidase enzyme, in mini-Tn5 transposon
      derivatives for use in Gram-negative bacteria. These mini-Tn5 elements allow
      simultaneously monitoring of gene expression and localization of the marked
      bacteria. Introduction of the resultant mini-Tn5 transposons into Rhizobium etli,
      Azospirillum brasilense and Pseudomonas stutzeri allowed us to visualise the
      interaction of these bacteria with their host plant. The dual-marker mini-Tn5
      transposons constitute a powerful new tool for studying gene expression and
      ecology of bacteria in the environment and during the interaction with plants.

PMID- 10076636
TI  - To clone or not to clone--the debate continues.

PMID- 10076637
TI  - Reform of legislation covering deliberate transmission of infectious disease.

PMID- 10076638
TI  - Alcohol consumption worldwide--and the relationship with cancer.

PMID- 10076639
TI  - Albumin: what influences its level in the blood?

PMID- 10076641
TI  - Health promotion, environmental health and Agenda 21.
AB  - In 1992, at the Rio Earth Summit, many governments, including our own, committed
      themselves to developing local strategies for sustainable development in the form
      of Local Agenda 21. Sustainable development is discussed, as is the philosophy
      and practice of health promotion and environmental health. Common approaches are
      identified and the links in relation to key areas of activities, strategies,
      values and principles are outlined. Finally, recommendations are made and
      conclusions drawn in relation to the overlap between environmental health action,
      Agenda 21 strategies and health promotion practice.

PMID- 10076640
TI  - Burden of illness review of obesity: are the true costs realised?
AB  - Obesity can no longer be viewed as merely a cosmetic or social problem, but must
      be acknowledged as a serious disease, responsible for the premature death and
      morbidity of millions and for significant expenditure of limited healthcare
      resources. In addition, there are significant costs to the individual with regard
      to social status and quality of life. It has been argued that obesity is one of
      the most important preventable causes of ill health in the UK today. This is
      especially important when one considers that the incidence of obesity is actually
      rising, with 13% of men and 16% of women in the UK in 1997 being obese. To begin
      treating such a disease it is essential to raise awareness of this problem, not
      only from the associated morbidity and mortality risks that have been well
      documented, but the socio-economic and psychological costs. This paper reviews
      the literature available globally, giving some measure of the magnitude of the
      associated burden of illness.

PMID- 10076642
TI  - Smoking, diabetes and hyperlipidaemia.
AB  - The epidemiological evidence linking smoking with insulin resistance is
      considerable. This evidence is even more convincing because there is a dose
      response relationship between smoking and the risk of non-insulin dependent
      diabetes (NIDDM). Similarly, there is a time-dependent decrease in risk of NIDDM
      for those who quit smoking. Insulin resistance (in the form of impaired glucose
      tolerance, IGT) may precede the development of NIDDM. There is a biochemical
      basis for the smoking-IGT/NIDDM relationship. Smoking increases the risk of
      developing diabetic complications like nephropathy, neuropathy and retinopathy
      Smoking is also an independent risk factor for myocardial infarction and all
      cause mortality in NIDDM. Smokers are both insulin resistant and lipid
      intolerant. Smoking cessation increases circulating high density lipoprotein
      (HDL) and reduces low density lipoprotein (LDL) levels, despite weight gain.
      Those providing advice or treatment to improve cardiovascular risk factors should
      be aware of these smoking-related harmful effects. This is especially true if IGT
      is underdiagnosed despite the fact that this condition increases the risk of
      vascular events. Explaining that smoking increases the chance of developing
      diabetes as well as raising 'blood fat' levels may convince more smokers to quit.

PMID- 10076643
TI  - Some peoples' psychological experiences of attending a sexual health clinic and
      having a sexually transmitted infection.
AB  - This study considers aspects of the experiences of a group of people attending a
      sexual health clinic and receiving the diagnosis of a sexually transmitted
      infection (STI). The study was conducted in the form of action research using a
      qualitative approach. Participants consisted of eight attenders at a sexual
      health clinic who had been diagnosed with a sexually transmitted infection.
      Counselling skills and techniques were used throughout semi-structured interviews
      to explore participants' feelings about these issues. Thematic analysis was used
      to generate themes of importance to the participants. Some people who had been to
      a sexual health clinic and received a diagnosis of a sexually transmitted
      infection were found to experience feelings of anxiety, stigma and isolation.
      This study is of value to all those working in the field of sexual health with an
      interest in understanding the issues that are important to the client group.

PMID- 10076644
TI  - Lessons to be learned: a case study approach. Primary hyperparathyroidism
      simulating an acute severe polyneuritis.
AB  - The case is presented of a 65 year old lady with recent onset of neuromuscular
      manifestations, comprising paraparesis, areflexia and unsteady gait, along with
      episodes of slurring of speech and diplopia, later confirmed to be due to severe
      hypercalcaemia--which itself was caused by primary hyperparathyroidism.
      Restoration of normocalcaemia, by means of rehydration and bisphosphonate
      therapy, resulted in clinical improvement--whilst subsequent parathyroidectomy
      was followed by complete resolution of all symptoms. In order to make prompt
      differentiation between the neurological sequelae of hyperparathyroidism and a
      primary neurological disorder, a high index of suspicion is required. An urgent
      serum calcium assay, as part of a bone profile, is mandatory in patients who
      present with neurological symptoms--especially the elderly, amongst whom
      hyperparathyroidism is especially common.

PMID- 10076645
TI  - The growing influence of non governmental organisations (NGOs) in international
      health: challenges and opportunities.
AB  - The growing influence of non governmental organizations (NGOs) in international
      health is occurring in the face of major challenges and opportunities. These
      challenges include the continued increases in global poverty status, the growing
      influence of private-funded health systems, the need for sustainability of
      external-funded programs, and the clamour for community participation in the
      planning and management of external-funded programs. Opportunities include the
      near universal recognition of the indispensable roles of NGOs by bilateral
      institutions and governments, the current emphasis on global trade by developed
      countries, and the need to develop political and economic systems that are
      equitable and promote social development. This article is an overview of these
      challenges and how these challenges can become excellent opportunities for NGOs
      to improve the health and social development of target communities in developing
      countries.

PMID- 10076646
TI  - Historical perspectives on health. A historical approach to study of the function
      and dysfunction of the thyroid gland realised?

PMID- 10076647
TI  - Re: Essential oils and 'aromatherapy' their modern role in healing.

PMID- 10076648
TI  - Re: Sexually transmitted diseases among women in Coventry.

PMID- 10076649
TI  - Our healthier nation.

PMID- 10076650
TI  - Carbon monoxide: the invisible killer.
AB  - Carbon monoxide (CO) is a colourless, odourless and tasteless gas. It is emitted
      when carbon containing compounds are incompletely combusted. This paper reports
      on concentrations of CO in the environment in relation to anthropogenic emission
      sources and assesses the extent of the health hazard from this common air
      pollutant. It includes the results of CO monitoring in a variety of locations in
      south west London. The conclusion is that indoor emission sources present a
      greater and more insidious health risk than do outdoor emission sources. Methods
      for reducing the dangers it poses are briefly summarised.

PMID- 10076651
TI  - Food consumption patterns of adults in the United Arab Emirates.
AB  - The objectives of this study were to determine the food consumption patterns of
      Emirati men and women over 20 years of age and to explore the association of age
      and sex with food intake. A proportional random sample of 1,122 men and 1,090
      women was obtained from all the seven Emirates of the United Arab Emirates (UAE).
      The findings showed a significant difference in food frequency intake between men
      and women, and also between young (20-49 years) and old (50 years and above)
      subjects. In general the consumption of fresh fruit and vegetables and of milk
      was low. This is a source of concern as these foods are useful sources of
      vitamins and minerals. Elderly people were more likely to consume traditional
      foods such as fish and laban (diluted yoghurt) than young people. Modification of
      dietary habits should be considered in any nutrition education programme for the
      public in the UAE.

PMID- 10076652
TI  - Cigarette smoking and erectile dysfunction.
AB  - Erectile dysfunction (ED, formerly referred to as impotence, is a common
      (especially in diabetic and older men) and distressing condition. Several risk
      factors have been identified; among these are smoking, hyperlipidaemia,
      hypertension and diabetes mellitus. These risk factors are shared with
      atherosclerotic vascular disease (e.g. ischaemic heart disease). This observation
      underlies a common vascular pathology. Smoking may cause ED by several
      mechanisms, including adversely affecting intrapenile blood flow. It is important
      to be aware of the link between smoking and ED since this information may
      motivate some male smokers to quit. In this context, it is important to be aware
      of the link between smoking and ED since this information may motivate smokers to
      quit. In this context, it is relevant that there is evidence that quitting may
      restore/improve erectile function.

PMID- 10076653
TI  - The effects of war on mental health.
AB  - A hundred claimants, almost entirely ex-service personnel who claimed sequelae
      following their war service, were assessed for their war pension rights. The
      difficulties they experienced are discussed, especially as regards physical
      symptoms, pre-morbid personality, length of time since event, effects of
      different locations, memory difficulties, concomitant old age etc. In spite of
      these difficulties it is still important to attempt to be unbiased and try to
      give the DHSS guidance in their difficult job.

PMID- 10076654
TI  - Rises in schoolchildren's anthropometry: what do they signify in developed and
      developing populations?
AB  - Recent reports indicate continuing rises in the height and weight of
      schoolchildren in both developed and developing populations. Also indicated are
      increases in the body mass index of children, and of adults, despite all public
      health warnings to the contrary, as well as personal desires of huge proportions
      of children, and of adults, to be slim. A little researched question concerns
      which level of schoolchildren's growth is consistent in later life with least
      occurrence of degenerative diseases. In developing populations, lack of knowledge
      prevails regarding the current and future health of the large proportions, and
      huge numbers, of schoolchildren who, judging from Western anthropometric
      standards, are categorized as suffering from mild to moderate malnutrition. It is
      questioned whether greater growth is essentially better. As to the future, in
      Western and in urban developing populations, attempts to control greater
      attainment of weight for height in schoolchildren, as well as adults, are
      unlikely to be rewarding, due to unpopularity of a 'prudent' diet on the one
      hand, and the still diminishing physical activity on the other. Notwithstanding,
      educational and other efforts to improve the composition of diets and encourage
      greater physical activity must be energetically pursued.

PMID- 10076655
TI  - Promoting oral health in institutionalised older adults: a nursing perspective.
AB  - Current demographic trends necessitate that increased attention be paid to
      problems arising in the older population. One such area relates to the oral
      cavity, which may be affected by both the effects of aging and the effects of
      disease and illness. Yet the evidence shows a significant lack of adequate oral
      care, which may create major problems for affected individuals, causing oral and
      dental problems that may, in turn, predispose to nutritional deficiencies,
      communication difficulties and devastating dental disease (Ogle, 1982). This
      paper reviews the literature pertaining to this complex subject, concluding that
      although nurses have an important role in providing effective oral care for the
      institutionalised patient, it is difficult to identify appropriate techniques,
      agents and tools with which to provide such care. Further research in this field
      is undoubtedly needed.

PMID- 10076656
TI  - Lessons to be learned: a case study approach--a case of temporal arteritis.
AB  - A 71-year-old male presented with a history of sudden partial visual loss in the
      right eye with an inferior visual field defect over the past 3-4 days. He had no
      history of headache or of facial pain. Clinical examination confirmed that vision
      on the right side was reduced to 6/18 and on the left to 6/12. The right eye
      showed a relative afferent pupillary defect. There was no other abnormality of
      the anterior segment of either eye. The right retina showed a pale swollen optic
      disc and a provisional diagnosis of anterior ischaemic optic neuropathy (AION)
      was made. An urgent erythrocyte sedimentation rate (ESR) was ordered and the
      patient was asked to return to the eye clinic in one month. However, 16 days
      later--when it was first recognised that his ESR was elevated to 75 mm in the
      first hour--the patient was recalled immediately in order to commence systemic
      steroid treatment; but regrettably, by this time, his right eye had become
      totally blind. In this case, although the attending doctor made a correct
      clinical diagnosis on presentation, he failed to act upon the result of the blood
      test.

PMID- 10076657
TI  - Follow-up of sporadic cases of food-borne infection: comparison of a postal
      questionnaire with a personal visit.
AB  - The aim of the study was to evaluate the follow-up of sporadic cases of suspected
      food-borne illness by either a postal questionnaire or a personal visit by
      environmental health staff. This was achieved by comparing the practice in two
      authority areas within the West Pennine Health Authority in the north west of
      England. We included all identified cases of suspected food poisoning,
      campylobacteriosis, cryptosporidiosis, salmonellosis and dysentery occurring in
      the district between 1 July and 30 September 1996. The main outcome measures
      were: (1) the proportion of all cases which were successfully followed-up by each
      method; (2) the timeliness of follow-ups; (3) qualitative estimation by
      environmental health staff of the data obtained. Visiting by environmental health
      staff was successful in obtaining information from 76.3% (106/139) of cases,
      while the postal questionnaires elicited a 52% (50/96) response rate. We found
      that 70.5% of visits occurred within one week of notification. Although 69.8%
      (67/96) of questionnaires were issued within one week of notification, only 16%
      of replies to the questionnaire were received within this period. The information
      provided on the returned questionnaires was found by environmental health staff
      to be generally as useful as that obtained by visiting.

PMID- 10076658
TI  - Historical perspectives on health. Aspects of public health up to Chadwick.

PMID- 10076659
TI  - The submission from the Royal Society for the Promotion of Health on the proposed
      Food Standards Agency.

PMID- 10076660
TI  - Why the NHS needs dentistry. British Dental Association and the University of
      York Department of Health Studies, Harrogate, 23rd April 1998.

PMID- 10076661
TI  - Review of the Nurses, Midwives and Health Visitors Act. Conference held on 23rd
      April 1998 at the Royal College of Surgeons of London.

PMID- 10076662
TI  - Re: Severe hypoglycaemia in insulin-dependent diabetes mellitus: living to tell
      the tale (lessons to be learned: a case study approach)

PMID- 10076668
TI  - Assessing practice nurses' change in nutrition knowledge following training from
      a primary care dietitian.
AB  - The expanding role of the Primary Health Care Team (PHCT) has led to more
      opportunities to offer dietary advice to patients. However, members of the PHCT
      appear to lack nutritional knowledge and confidence when giving dietary advice.
      This work assesses the changes in Practice Nurses' (PNs) nutrition knowledge and
      confidence when giving dietary advice to patients, following training from a
      dietitian. Base line nutrition knowledge of PNs and their confidence when giving
      dietary advice was assessed in 30 GP Practices by questionnaire. Following
      Practice-based training from a dietitian, change in knowledge and confidence was
      assessed using the same questionnaire. Paired and unpaired analysis was carried
      out on the PN's knowledge and confidence scores respectively. Nutrition knowledge
      increased significantly after training. The mean difference (95% confidence
      interval) pre- and post-training was 11.6 (7.8, 15.4). After training 88% of PNs
      reported having good or excellent confidence compared with 27% before training
      (chi-squared test p < 0.001). Nutrition training from a dietitian improves
      nutrition knowledge of PNs. It also improves their confidence and is recommended
      to support their role in providing accurate and consistent dietary advice to
      patients.

PMID- 10076669
TI  - Smoking and urological disease.
AB  - It is important to realise that virtually every part of the body, including the
      urological system, is adversely affected by smoking. Smoking is the most
      important known preventable cause of urinary bladder cancer and is also
      associated with a risk of prostatic and renal cancer. The exact mechanism by
      which smoking increases the incidence of urological malignancy is not known. One
      possibility is that chemicals in cigarette smoke inhibit the synthesis of
      cytoprotective eicosanoids. Deficient local protection, against the hostile
      environment caused by the presence of urine, could then encourage the process of
      carcinogenesis. Smoking is a powerful predictor of erectile dysfunction;
      cessation may restore normal function. Cigarette smoke also exerts adverse
      effects on sperm motility and count. Although there is no convincing evidence of
      reduced fertility in male smokers, it is advisable for men to quit smoking should
      they have marginal semen quality and wish to start a family. Smoking causes
      substantial urological pathology; these facts can be used to convince patients
      with urological problems to quit smoking.

PMID- 10076670
TI  - Simulating hospital patient flows.
AB  - This case study development has benefited by the use of clear on-screen logic
      which has facilitated useful discussions between the analyst and end-users. The
      screen displays enable a realistic depiction of a system to be developed. A
      simple first model was gradually made more realistic in a step-by-step process
      involving both analyst and end-users. The investigation is continuing and the
      model is being further refined. Data collection is underway, and system data will
      be used to provide the model's input parameters of arrival and service rates.
      Times and lengths of queues of patients and total time in the system will be
      compared with their model equivalents. The resulting model is likely to be
      acceptable to the end-users because of their involvement in its development. This
      involvement has been facilitated by a simulation environment which enables on
      screen iconic representations of system components to be created by analyst and
      end-user together.

PMID- 10076671
TI  - Health promotion in a hospital ward; reality or asking the impossible?
AB  - The hospital ward environment poses challenges for health promotion which will
      require not only increased multiprofessional collaboration, but a new
      appreciation of the capabilities of each member of the ward team. This paper
      discusses the application of one model of health promotion suitable for use in
      this setting and highlights the advantages of utilising such an approach.

PMID- 10076672
TI  - Food, nutrition, anti-social behaviour and criminality.

PMID- 10076673
TI  - Painting collections in hospitals: humanity in medicine.

PMID- 10076674
TI  - Historical perspectives on health. Origins of blood analysis in clinical
      diagnosis.

PMID- 10076676
TI  - The submission from The Royal Society for the Promotion of Health on Government
      consultation document "Our Healthier Nation".

PMID- 10076675
TI  - Lessons to be learned: a case study approach diuretic therapy and a laxative
      causing electrolyte and water imbalance, loss of attention, a fall and subsequent
      fractures of the tibia and fibula in an elderly lady.
AB  - The case is described of a hitherto well, alert and intelligent lady of 85 years
      of age, who commenced medication with diuretics--prescribed for mild congestive
      cardiac failure; she developed constipation consequent upon the diuresis and
      dehydration thereby provoked. As a result she began to take, unknown to her
      general practitioner, regular and increasing amounts of laxatives. At about this
      time she was noted by her son to become "rapidly senile"--with the result that
      she fell on account of losing her normally good concentration and attention; she
      sustained fractures of the right tibia and fibula. Shortly after admission to
      hospital she was premedicated, anaesthetised and operated upon, following which
      there was a postoperative regimen comprising several litres of low sodium
      isotonic infusions, all given intravenously. She was found at this point to be
      severely hyponatraemic with a low serum osmolality, but following the institution
      of water restriction rapidly improved as her serum sodium rose again; there was
      an accompanying massive diuresis as the previously retained water was voided.
      Concomitant with the serum sodium rise her mental concentration and attention
      regained their former levels. The biochemical and cellular mechanisms underlying
      this patient's symptoms are discussed.

PMID- 10076677
TI  - Malnutrition in hospitals: a report on the Professorial Inaugural Lecture,
      delivered by Professor Susan Holmes presented at Canterbury Christ Church
      College, June 17th 1998.

PMID- 10076678
TI  - Re: Sexually transmitted diseases among women in Coventry.

PMID- 10076686
TI  - The influence of ispaghula husk on bowel habit.
AB  - Frequency of defaecation, faecal form, straining at the start and end of
      defaecation, feelings of incomplete evacuation of faeces and urgency of
      defaecation were recorded in 69 healthy volunteers during three distinct 28-day
      study phases: pre-treatment, treatment with ispaghula husk and post-treatment.
      During treatment there was a significant increase (P < 0.001) in stool frequency
      and significant decreases in straining at the start (P < 0.001) and end (P <
      0.001) of defaecation and in feelings of incomplete evacuation (P < 0.001). There
      was evidence of a beneficial residual effect after treatment had stopped. There
      are indications that ispaghula husk (Fybogel Orange) is of benefit in relieving
      constipation symptoms in apparently healthy people.

PMID- 10076687
TI  - Incidence of reported cerebral concussion in adult taekwondo athletes.
AB  - The purpose of the present study was to assess the exact conditions under which
      cerebral concussions occur in full-contact taekwondo competition. Injury data
      were collected by project staff and tournament medical personnel with simple
      check-off forms that describe the athlete and nature, site, circumstances and
      severity of the injury. The Mann-Whitney U test was used to determine the
      difference in injury rate between men and women. The men (7.04/1,000 athlete
      exposures) sustained more cerebral concussions than the women (2.42/1,000 athlete
      exposures) (p < 0.001). The dominant injury mechanism in both the males and
      females was receiving a blow (6.46/1,000 athlete-exposures and 2.42/1,000 athlete
      exposures for the men and women, respectively).

PMID- 10076688
TI  - Pruritus in children.
AB  - Pruritus is the most common of all dermatological complaints. Although pruritus
      is usually due to a primary skin disease, it may be a manifestation of a systemic
      illness. The majority of causes can be diagnosed from the history and physical
      examination. Laboratory investigations are usually not necessary. Treatment
      should be directed at the underlying cause whenever possible.

PMID- 10076689
TI  - Intracranial pressure monitoring by time domain analysis.
AB  - This paper discusses the developments in the assessment of intracranial
      hypertension in humans and recent research carried out by the authors on the
      techniques for the non-invasive measurement of intracranial pressure. A brief
      historical review sets the scene with regard to clinical and invasive methods for
      the observation of intracranial pressure and goes on to look at non-invasive
      techniques for measuring blood flow and pressure from which it is proposed that
      intracranial pressure can be predicted. Although a simulation and a frequency
      domain analysis of the dynamics of the human brain has been carried out, this
      paper concentrates only on the time domain experiments and analysis. The time
      domain analysis uses the cross-correlation of the non-invasive blood flow of the
      middle cerebral artery with blood pressure measurements and their varying phase
      shift with trauma characteristics to make predictions of intracranial pressure
      trends that lead to pathologically dangerous conditions. The paper concludes with
      a section concerning the development of software and associated graphical
      displays that could inform staff of trends in intracranial pressure and life
      threatening conditions so that immediate action can be taken.

PMID- 10076690
TI  - Help with HACCP.
AB  - An evaluation of a new short HACCP course is presented as a case study involving
      a group of representatives from Residential Homes. HACCP awareness was assessed
      before and after the course. Following the course, participants were encouraged
      to collaborate to produce a generic HACCP model suitable for their industry
      sector. Work was co-ordinated by the course tutor and support was provided for
      participating businesses who wished to customize the model and implement their
      own HACCP system. The course was judged favourably by the participants and the
      tutor, but all recommended that an elementary knowledge of food hygiene be a pre
      requisite for participation on the course. The course increased HACCP awareness
      and the practical exercise increased the confidence of the participants to apply
      the HACCP principles. By working together the group produced a model, which half
      have since employed as the basis of their own HACCP system.

PMID- 10076691
TI  - Historical perspectives on health. The history of liquorice: the plant, its
      extract, cultivation, commercialisation and etymology.

PMID- 10076692
TI  - Lessons to be learned: a case study approach. An unusual case of alveolar
      deposition from swallowing metallic mercury in an attempt at self-poisoning.
AB  - The authors report a case of deliberate self-poisoning in a drug addict who
      swallowed elemental mercury: in so doing he inadvertently acquired a permanent
      diffuse deposition of mercury particles throughout both lung fields. Swallowed
      mercury should be relatively harmless in small quantity but the high specific
      gravity and free flowing properties of elemental mercury allowed it to overcome
      the normal swallowing pathways--such that some of it passed into the bronchial
      tree instead of passing harmlessly through the gut. In that site its significant
      vapour pressure, together with its potential for oxidation to inorganic mercury-
      which may, in turn, be absorbed across the alveolar membrane, gives high
      potential for mercury poisoning.

PMID- 10076693
TI  - The submission from The Royal Society for the Promotion of Health on the
      communication from the Commission on the Development of Public Health Policy in
      the EC.

PMID- 10076694
TI  - Initial assessment of children's ability to climb stair guarding.
AB  - This study examined the ability of children aged between four and six years to
      climb stair guarding set at the minimum height for domestic handrails recommended
      in the guidance given in Approved Document K that supports the Building
      Regulations in England and Wales. The purpose was to assess the adequacy of such
      safety guidance. Simulated guarding was set up at an indoor play centre and
      behaviours examined in two groups of children. Observations were made during free
      play and during solicited climbing. Results indicate that the majority of
      children aged between four and six years can climb onto or over stair guarding
      unassisted. Younger children are influenced and frequently abetted by their
      elders in climbing, behaviour which may be replicated in the home environment.
      Three distinct climbing strategies are observed: the body hoisted in a semi-prone
      position onto the top of the guarding; the body lifted by arms above the height
      of the guarding enabling a kneeling position on the top of the guarding; and, the
      knee bent against the side of the guarding to gain the added height required to
      make the climb. It was noted that older or taller children tend to rely on
      height, leg length or each whilst climbing whereas younger children appear to
      depend more on strength. A re-examination of safety guidance in relation to
      barrier climbability by children is recommended, and has started at BRE.

PMID- 10076695
TI  - The management of diabetes at primary level in South Africa: the results of a
      facility-based assessment.
AB  - Diabetes is a widespread condition in South Africa and is often managed at
      primary level health facilities. This study aimed to assess the quality of
      diabetes management using a rapid assessment approach, focusing on three
      indicators as proxy measurements of quality: the regularity of blood glucose
      level (BGL) measurement; the percentage of patients whose BGLs were within
      'acceptable' limits (under 10.0 mmol/l) on at least 75% of visits; the rate at
      which action was taken in response to high BGLs. Five sites were included in the
      study, including public and private, doctor- and nurse-based facilities. A total
      of 128 records were examined. Only 33% of all records were found to be well
      managed according to the study criteria. None of the individual facilities were
      found to have more than 40% of patients achieving BGLs within the study limits.
      Some obstacles to good glycaemic control were costs to patients, transport
      problems, a lack of health education and shortcomings in clinical expertise.
      Policy implications and recommendations are suggested.

PMID- 10076696
TI  - Respiratory symptoms and lung function in garage workers and taxi drivers.
AB  - The aim of this study was to determine the prevalence of some respiratory
      symptoms and possible diseases among occupationally-exposed garage workers and
      taxi drivers. This study involved 158 garage workers and 165 taxi drivers,
      matched for age, sex, nationality and duration of employment. The mean age of 158
      Indian subcontinent garage workers was 34.4 +/- 10.4 years; their mean height and
      weight were 167.7 +/- 6.6 cm and 72.0 +/- 12.3 kg respectively, and the mean
      duration of employment garage workers was 8.8 +/- 7.6 years. The mean age of 165
      Indian subcontinent male taxi drivers was 34.5 +/- 7.7 years; their mean height
      and weight were 168.7 +/- 6.1 cm and 71.3 +/- 12.6 kg respectively; and the mean
      duration of employment was 7.5 +/- 5.4 years. The data on chronic respiratory
      symptoms showed that garage workers had higher prevalence of symptoms than taxi
      drivers being significantly greater for chronic phlegm, (p < 0.007); dyspneoa (p
      < 0.001); and sinusitis (p < 0.03). A higher prevalence of all acute symptoms was
      recorded in garage workers than in taxi drivers, although the differences were
      significant only for throat (p < 0.02), hearing problems (p < 0.002); nose
      (dryness, bleeding and secretion) (p < 0.008); and low back pain (p < 0.05).
      Almost all forced spirometric tests in the exposed garage workers were lower than
      in taxi drivers. The results of stepwise multiple regression analysis showed that
      only phlegm, sinusitis, hearing problems, nasal catarrh, throat, low back pain,
      smoking and FEF25-75, variables were statistically significant predictors as risk
      factors. In conclusion, the present study suggests that a high prevalence of
      respiratory symptoms is associated with exposure to motor vehicle exhaust
      emission in garage working places. Long-term working as garage workers in the
      United Arab Emirates (UAE), may be associated with the development of chronic
      respiratory symptoms and have effects on their daily life and health.

PMID- 10076697
TI  - A smoking cessation counsellor: should every hospital have one?
AB  - The study was performed in order to ascertain the sustained smoking cessation
      rate in hospital patients who received a structured programme of advice and
      support from a counsellor and to estimate the cost-effectiveness of such an
      intervention. Hospital in-patients out-patients were referred by their
      physician/surgeon to the smoking cessation counsellor who provided advice to
      reinforce that of the doctor and gave support by repeated follow-up sessions,
      weekly in the first month and thereafter at three, six and twelve months. Of
      1,155 patients referred to the counsellor, 114 (13%) failed to keep the first
      appointment and 348 (30%) attended for advice on one occasion only. Among the
      latter, the self-reported sustained cessation rate at one year was 5%. In the 663
      patients who participated in the programme the validated (expired air CO) 12
      month, sustained cessation rate was 21%. Allowing 7.5% success rate among
      patients receiving a physician's advice only, the cost of each additional success
      achieved as a result of the programme is 851 Pounds and the cost per life year
      saved is between 340 Pounds and 426 Pounds. Assuming that after one year's
      abstinence relapse rates are relatively small, this represents a sound investment
      in the light of the cost of treating patients with smoking-related illnesses and
      compares favourably with other smoking cessation strategies and health care
      interventions.

PMID- 10076698
TI  - Ballet dancers--pregnancy outcomes.
AB  - Ballet dancers have been observed to have increased difficulties in pregnancy and
      labour. This article looks at this anatomically, physiologically and socially. It
      suggests that, with the intervention of appropriate health care professionals,
      (for example, nutritionists, doctors, nurses and midwives), the ballet dancers'
      quality of life, health status and professional performance can be improved.

PMID- 10076699
TI  - The social responsibilities of the physician.
AB  - The 1997 Keynote Address for the White Coat Ceremony at St George's University
      School of Medicine indicates the importance of social medicine in the work of the
      physician and urges the students beginning the study of medicine to devote
      themselves to equitable provision of medical care, to prevention of disease and
      promotion of health, and to promotion of social well-being.

PMID- 10076701
TI  - Lessons to be learned: a case study approach. Finger discoloration due to silver
      nitrate exposure: review of uses and toxicity of silver in clinical practice.
AB  - A 29 year-old lady attended the Accident and Emergency Department of a District
      General Hospital complaining of increasing black discoloration of the tip of her
      left middle finger; the appearance resembled that of gangrene. However, it was
      established that she had been applying silver nitrate to her finger, as
      prescribed by her general practitioner for the treatment of a small granuloma.
      Hence, the true diagnosis was of localised tissue necrosis, secondary to
      application of the silver nitrate sticks. On early discontinuation of the
      therapy, there was complete recovery. In consequence, it is recommended that the
      practice of unsupervised local application of silver nitrate to the fingers
      should be discontinued. Opportunity is taken herein to review the uses of silver
      nitrate in clinical situations--and of silver in any of its many other forms-
      together with their respective adverse effects.

PMID- 10076700
TI  - Historical perspectives on health. Semmelweis: a lesson to relearn?

PMID- 10076702
TI  - Contraception today. A report on the Royal Society for the Promotion of Health
      conference. Held on Thursday 8th October, 1998, Hamilton House, London.

PMID- 10076703
TI  - Regulation of IgE synthesis: the molecular basis and implications for clinical
      modulation.
AB  - The reagenic antibody in the sera of atopic individuals, first described by
      Prausnitz and Kustner and later determined to be Immunoglobulin (Ig) E by the
      Ishizakas, plays a critical role in the pathogenesis of allergic disease.
      Investigation into the cellular basis of IgE regulation has provided important
      insights into a disease process that affects up to 30% of the population world
      wide. Over the last decade, the molecular events regulating IgE synthesis have
      been actively investigated. In this review, we will discuss the various
      components of this system including the cells, cytokines, signal transduction
      events, and molecular mechanisms that participate in human IgE synthesis and
      explore rational therapeutic approaches directed at the modulation of these
      systems.

PMID- 10076704
TI  - Immunologic basis and management of steroid-resistant asthma.
AB  - Although the majority of patients with asthma respond favorably to inhaled and
      systemic glucocorticoids, up to 25% of patients with difficult-to-control asthma
      have poor clinical responses to high doses of systemic glucocorticoids. Early
      identification of these patients is required to minimize serious side effects
      from long-term systemic glucocorticoid therapy in patients who are insensitive to
      such therapy. Recent studies indicate that these individuals have developed
      diminished glucocorticoid receptor ligand and DNA binding affinity as the result
      of poorly controlled immune activation potentially triggered by allergens or
      infection. The current review will examine the immune mechanisms underlying
      glucocorticoid resistance and discuss the management of this challenging group of
      patients.

PMID- 10076705
TI  - Is month of birth a risk factor for subsequent development of pollen allergy in
      adults?
AB  - A comparison of the date of birth of 1501 adult patients with severe seasonal
      respiratory allergy (allergic rhinitis or bronchial asthma) due to parietaria,
      olive, and grass pollens with the expected births within 2,020,420 births in
      South Greece during the same period, was performed. The relative risk for
      developing respiratory allergy was characteristically increased in those born in
      a specific period of time different for each pollen. The relative risk for
      parietaria was increased (1.47) in those born in March; for olive it was 1.6 for
      May; 1.2 for April; and 1.4 for March, while the relative risk for grasses was
      1.2 in those born in June and July. These findings are indicative of the
      importance of the month of birth; that is, the early exposure to pollens, for the
      development of respiratory allergy to certain pollens during adulthood. Because
      our findings do not directly correlate completely with the aerobiology studies on
      pollen calculation in Athens' atmosphere, we supposed that other environmental
      factors, e.g., the local intensity of the first pollination or the influence of
      weather conditions, may contribute to the final development of respiratory
      allergy as well. The most impressive finding was the significant influence of the
      month of birth in the development of respiratory allergy due to parietaria and
      olive pollens during adulthood.

PMID- 10076706
TI  - What makes a child allergic? Analysis of risk factors for allergic sensitization
      in preschool children from East and West Germany.
AB  - Earlier epidemiologic studies within Germany found a higher frequency of allergic
      sensitization in West Germany. The reasons for that and the role of environmental
      factors in the process of allergic sensitization are not fully understood. This
      study aimed to determine the prevalence of positive skin-prick test results 5
      years after unification and to investigate risk factors for allergic
      sensitization in preschool children. A total of 1235 children (5-6 years) from
      two West and five East German locations were skin-prick tested after the
      compulsory school entrance examination. Six common aero- (birch, grass, mugwort
      pollen, cat, HDM, alternaria) and two food allergens (egg, milk) were used and
      additional information was obtained by questionnaire. Of the tested children
      23.3% exhibited at least one positive reaction. The prevalence of sensitization
      to the single allergens was as follows: grass (14.4%), birch (6.6%), mugwort
      pollen (4.5%), cat (8.5%), HDM (5.5%), alternaria (4.9%), egg (2.8%), and milk
      (3.9%). In the crude analysis significantly more children were sensitized in the
      East German city Magdeburg (40.2%) compared to the West German control region
      Borken (23.5%) (OR 2.20, CI 1.47-3.29). Dampness and visible molds were reported
      in 8.8% of all households, but significantly more often for East German
      apartments (10.3% versus West Germany 1.9%, OR 5.85, CI 2.55-16.53). Dampness and
      molds were associated with a higher frequency of sensitizations (40.6% versus
      27.6% in unaffected homes). After controlling for sex, parental atopy, SES,
      family size, and smoking during pregnancy, this association remained
      statistically significant (OR 1.93, CI 1.19-3.12). With regard to single
      allergens, dampness and visible molds were significantly associated with
      sensitization to HDM (OR 3.37, CI 1.63-6.96), cat (OR 3.19, CI 1.11-5.74), and
      mugwort pollen (OR 2.86, CI 1.29-6.35). In addition, family size was inversely
      and linearly associated with the frequency of sensitization (OR for four, three,
      and two-person households: 1.10 (0.74-1.63), 1.57 (1.06-2.42), 2.70 (1.39-5.24),
      respectively, when compared to family size of five or more). Neither parental
      predisposition for atopic diseases nor parental education level influenced the
      prick test reactivity. We conclude that in addition to genetic predisposition,
      environmental factors like indoor climate and probably infectious stimuli (family
      size) play an important role in the process of allergic sensitization in
      children.

PMID- 10076707
TI  - An attempted prospective testing of an asthma severity index and a quality of
      life survey for 1 year in ambulatory patients with asthma.
AB  - It has been recommended that allergist-immunologists use quality of life (QOL)
      surveys to document their "added value" in patient care. There are little cross
      sectional or prospective data regarding longer term follow-up of patients using
      QOL assessments and none associated with prospective use of an asthma severity
      index (ASI). Our objective was to identify clinical and psychological correlates
      of adverse asthma outcomes as assessed using the ASI survey. A 12 item QOL and a
      nine item ASI survey, spirometry, and history and physical were obtained from
      patients initially and then every 3 months for a year. The ASI was calculated as
      follows: one point for each emergency treatment of asthma if not in status
      asthmaticus, three points for each hospitalization for status asthmaticus, and
      six points for each intensive care admission or intubation. Patients were 56
      adults between ages 18 and 45 with asthma enrolled between May 1994 and February
      1996 with the intention to be reassessed quarterly for a year. At enrollment the
      56 patients had ASI scores for the previous 12 months ranging from zero to 30.
      The patient with an ASI of 30 did not return after the initial visit. Of the 13
      patients who completed the study, 12 patients had a zero ASI score over a 12
      month period; one patient who had an initial score of 26 finished with a score of
      one. There were no deaths throughout the follow-up period. Of the 43 patients who
      did not complete the study only six (13.9%) cited local managed care or primary
      care physician as taking over their care. Initial ASI scores were dichotomized
      (zero versus greater-than-zero) due to skewness. The forced expiratory volume in
      one second (FEV1), % predicted FEV1 and peak flow were not related significantly
      to the dichotomized ASI score. The strongest univariate predictor was the self
      assessment of asthma burden using a 78 mm visual analog scale. A two variable
      model included a query about bodily pain in the last 4 weeks and a self
      assessment of general health. The dropout rate was high but only 13.9% of such
      patients reported that managed care or primary care physicians were responsible.
      A two variable model was a strong predictor of asthma severity. The single best
      predictor of asthma severity was a visual analog scale based on the question "How
      do you think your asthma is?"

PMID- 10076708
TI  - Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss
      syndrome.
AB  - There are few reports regarding the measurement of cytokines and surface analysis
      of eosinophils in Churg-Strauss syndrome (CSS). To examine the pathophysiology of
      CSS, concentrations of cytokines in serum and bronchoalveolar lavage fluid
      (BALF), and surface antigens on peripheral blood eosinophils were analyzed in
      five patients with CSS. Concentrations of cytokines (interleukin-1 beta (IL-1
      beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), interleukin
      5 (IL-5) and granulocyte/macrophage colony stimulating factor (GM-CSF) were
      measured using ELISA. Surface antigens on eosinophils in peripheral blood were
      analyzed using flow cytometry. A concentration of interleukin-5 (IL-5) and TNF
      alpha in serum was detected in five cases; however IL-1 beta, GM-CSF, and IL-3
      were detected in 3 of 5, 2 of 5, and 1 of 5 patients, respectively. In BALF, TNF
      alpha and IL-5 were detected in 2 of 3 and 1 of 3 patients, respectively;
      however, neither IL-1 beta, GM-CSF, nor IL-3 was detected in any. Newly expressed
      surface antigens such as CD25, CD4, and CD69 were observed on peripheral blood
      eosinophils in five cases. CD54 and HLA-DR were expressed in 4 of 5 and 3 of 5
      patients, respectively. Eosinophils in peripheral blood are activated to various
      degrees, possibly depending on cytokine stimulation. This eosinophil activation
      may be related to the clinical stage of CSS.

PMID- 10076709
TI  - Gastroesophageal reflux: pathogenesis, diagnosis, and treatment.
AB  - Gastroesophageal reflux (GER) is a common problem confronting physicians involved
      in the care of children and adults. With the association of GER with asthma and
      chronic cough, physicians specializing in allergy/immunology require information
      on the pathogenesis, diagnosis, and management of GER. Eosinophilic esophagitis
      or eosinophilic gastroenteritis are poorly understood entities that may also lead
      to symptoms mimicking GER and are associated in many cases with underlying
      hypersensitivity of unknown immunologic mechanism.

PMID- 10076710
TI  - Chronic urticaria as a presenting sign of hairy cell leukemia.
AB  - Chronic urticaria is a common clinical disorder that is idiopathic in over 75% of
      cases. Less commonly, urticaria may be the presenting manifestation of an
      allergic or infectious disease, endocrinopathy, inherited syndrome, or autoimmune
      disorder. Rarely, urticaria may be a sign of underlying malignancy, including
      leukemia. C.C. is a 48-year-old white female who was referred for evaluation of
      recurrent urticaria for 3 years. The pruritic, erythematous wheals were pinpoint,
      and appeared to be precipitated by heat, stress, and effort. Prick tests were
      negative except to D. pteronyssinus. CBCs over the past 5 years revealed WBCs of
      2,300-5,000 cells/mm3. Skin biopsy revealed interstitial edema with infiltration
      of eosinophils and mast cells consistent with urticaria. The impression was
      probable cholinergic urticaria, for which hydroxyzine was prescribed with fair
      symptomatic control. One year later, she presented with bright red blood per
      rectum. Repeat physical examination revealed lymphadenopathy and splenomegaly.
      Subsequent laboratory studies showed pancytopenia. Endoscopy was normal except
      for small, nonbleeding hemorrhoids. Bone marrow biopsy revealed histologic
      evidence of hair, cell leukemia that was treated with 2-chlorodeoxyadenosine.
      Upon initiation of chemotherapy her pruritus and urticaria subsided. Recent CBC
      revealed Hgb 9.2 g/dL, platelets 290,000 cells/mm3, and WBC 4,100 cells/mm3.
      Peripheral blood smear showed no hairy cells.

PMID- 10076711
TI  - Asthma--a problem of health care delivery. Is it time for a new paradigm?
AB  - Asthma is common, results in extensive morbidity and occasional mortality, and is
      associated with highly variable outcome. A major factor influencing outcome
      relates to physician decision making. Subspecialty directed asthma management has
      been demonstrated to favorably influence outcome of asthma to a greater extent
      than any other variable in care. National guidelines appear to have had little
      impact on primary care of asthma despite their widespread distribution. As a
      substitute for those extremely comprehensive and extensive guidelines, a small
      number of measures can be identified that are both realistically applicable in
      the primary care setting while having the greatest impact on outcome. These low
      intensity high yield measures, if applied, can substantially reduce emergency
      care requirements and hospitalizations. Patients not responding adequately to
      those measures should be identified early and referred to subspecialists for
      subsequent ongoing management.

PMID- 10076712
TI  - Asthma among the famous. Alyce King Clarke (1915-1996) American vocalist. The
      King Sisters--the King Family musical performers.

PMID- 10076713
TI  - Asthma among the famous. Bill's asthma (1922) by Reeves Hansford English
      songwriter.

PMID- 10076714
TI  - More on cancer vaccine.

PMID- 10076715
TI  - Are physicians aware of what patients know about what physicians know?

PMID- 10076716
TI  - International Consensus Conference on high-dose therapy with hematopoietic stem
      cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury.

PMID- 10076717
TI  - Dendritic cells: a novel therapeutic modality.

PMID- 10076718
TI  - Applying evidence to the individual patient.

PMID- 10076719
TI  - Phase I trial of the combination of daily estramustine phosphate and intermittent
      docetaxel in patients with metastatic hormone refractory prostate carcinoma.
AB  - BACKGROUND: To apply our preclinical findings of cytotoxic synergy with the
      combination of estramustine phosphate (EP) and docetaxel as the basis of
      treatment of hormone refractory metastatic prostate cancer in man. To determine
      the optimal dosage and the toxicities of these two agents for future trials.
      PATIENTS AND METHODS: Seventeen patients with hormone refractory metastatic
      prostate cancer who were ambulatory with performance status < or = 2, normal
      marrow, renal and hepatic function were entered. Prior exposure to EP or a taxane
      were exclusion factors. EP was given orally at a dose of 14 mg/kg of body weight
      daily with concurrent docetaxel administered every 21 days as an intravenous
      infusion over 1 hour with dexamethasone 8 mg. PO BID for five days. EP dosages
      were kept static; docetaxel dosages were explored in a minimum of three patients
      per level for dosages of 40, 60, 70, and 80 mg/m2. Patients were evaluated
      weekly. Prostate specific antigen (PSA) was measured every three weeks. RESULTS:
      Five patients were entered at a docetaxel dose of 40 mg/m2, three at 60 mg/m2,
      six at 70 mg/m2, and three at 80 mg/m2. Only one patient had received prior
      chemotherapy. Grades 1 or 2 hypocalcemia and hypophosphatemia were seen at all
      dosage levels. Other grade 2 or less toxicities not related to dosage included
      alopecia, anorexia, stomatitis, diarrhea, and epigastric pain. Dose limiting
      toxicities (DLT) as grade 4 leukopenia and grade 4 fatigue were seen at 80 mg/m2.
      The phase II dose was defined at 70 mg/m2 with rapidly reversible leukopenia and
      minor liver function abnormalities. At this dosing level, dose intensity was 88%
      and 86% over consecutive cycles for docetaxel and EP, respectively. Two vascular
      events occurred at this dose level (70 mg/m2): one arterial and the other venous.
      PSA decreases greater than 50% from baseline were seen in 14 of 17 patients at
      all dosage levels. Four of the 17 patients demonstrated a complete biochemical
      response (PSA < or = 4 ng/ml). One patient had a partial response with measurable
      lung and liver lesions. CONCLUSION: EP given continuously with every three-week
      docetaxel at a dose of 70 mg/m2 is tolerable with evidence of antitumor activity
      based upon significant declines in PSA in the majority of patients and
      improvement of lung metastasis in one patient. Larger phase II studies of this
      combination in a homogenous population are warranted.

PMID- 10076720
TI  - Misunderstanding in cancer patients: why shoot the messenger?
AB  - AIM: We aimed to document the prevalence of misunderstanding in cancer patients
      and investigate whether patient denial is related to misunderstanding. PATIENTS
      AND METHODS: Two hundred forty-four adult cancer outpatients receiving treatment
      completed a survey assessing levels of understanding and denial. Doctors provided
      the facts against which patient responses were compared. Multiple logistic
      regression analyses determined the predictors of misunderstanding. RESULTS: Most
      patients understood the extent of their disease (71%, 95% CI: 65%-77%) and goal
      of treatment (60%, 95% CI: 54%-67%). Few correctly estimated the likelihood of
      treatment achieving cure (18%, 95% CI: 13%-23%), prolongation of life (13%, 95%
      CI: 8%-17%) and palliation (18%, 95% CI: 10%-27%). Patient denial predicted
      misunderstanding of the probability that treatment would cure disease when
      controlling for other patient and disease variables (OR = 2.20, 95% CI: 0.99
      4.88, P = 0.05). Patient ratings of the clarity of information received were also
      predictive of patient understanding. CONCLUSIONS: Patient denial appears to
      produce misunderstanding, however, doctors' ability to communicate effectively is
      also implicated. The challenge that oncologists face is how to communicate
      information in a manner which is both responsive to patients' emotional status
      and sufficiently informative to allow informed decision-making to take place.

PMID- 10076721
TI  - Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a
      unicentre randomized trial with a 124-month median follow-up. Institut Bergonie
      Bordeaux Groupe Sein (IBBGS).
AB  - BACKGROUND: Neoadjuvant chemotherapy improves overall survival and renders
      possible breast-conserving treatment in locally advanced breast cancer. It was
      necessary for this method to be evaluated in operable breast tumors too large to
      be treated immediately by conserving surgery. Initial results of this randomized
      trial were published in Annals of Oncology (1991). PATIENTS AND METHODS: Women
      with T2 > 3 cm or T3 N0-1 M0 breast tumors were treated by either initial
      mastectomy followed by adjuvant chemotherapy, or neoadjuvant chemotherapy
      followed by adjusted locoregional treatment. Chemotherapy was the same in the two
      arms. The prognostic and predictive factors of response to chemotherapy were
      analyzed. RESULTS: Conserving treatments were performed in 63% at the end of
      neoadjuvant chemotherapy and this rate had decreased to 45% at the median follow
      up of 124 months. Survivals are identical in the two treatment groups. Initial
      clinical tumor size < 40 mm, IHC-ER < 10% and Mib1 > 40% are predictive of tumor
      response to chemotherapy by uni- and multivariate analyses. For outcome
      prediction, c-erb-B2 > 0% is the independent prognostic factor for overall and
      metastasis-free survivals. CONCLUSION: Breast-conserving therapy can be performed
      in more than half of all cases without alteration of survival, despite a non
      negligible rate of local recurrences.

PMID- 10076722
TI  - Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor
      prognosis breast cancer.
AB  - PURPOSE: To prospectively evaluate the long term cardiac effects of high-dose
      epirubicin and cyclophosphamide given to women with early stage, poor prognosis
      breast cancer. PATIENTS AND METHODS: Women with stage 2 breast cancer and 10+
      nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer
      received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with
      peripheral blood progenitor cell and filgrastim support. Treatment was given
      every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy
      to the chest wall or breast, 25 of to the left side. Patients were assessed
      clinically regularly during chemotherapy and at least three times yearly after
      completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was
      assessed by radionuclide scan before therapy, after each cycle of chemotherapy,
      three months and six months after completion of chemotherapy, and yearly
      thereafter until relapse. RESULTS: Ninety-nine women were treated, and 92
      completed all three cycles of chemotherapy. The median age was 43 years (range 24
      to 60 years). All patients were included in this analysis. The median relapse
      free survival was 39 months (11 to 68 months). There was a significant fall in
      LVEF during chemotherapy. In general, there was no further deterioration in
      cardiac function from the third month after cessation of treatment, however there
      was substantial variation between individuals. 35 patients had at least one LVEF
      measure less than normal (< 50%), but the LVEF returned to normal in 20 of these
      with further follow-up. Cardiac dysfunction was not increased in women who
      received radiotherapy and was not different between cohorts given chemotherapy
      every three or every four weeks. One patient died of acute myocardial necrosis
      following the third cycle of chemotherapy. Two patients developed clinical
      evidence of cardiac failure, and another had radiological signs but was
      asymptomatic. One woman died of progressive cardiac failure, one recovered
      clinically but also developed recurrent breast cancer, while the third recovered
      after commencement of medical therapy. CONCLUSIONS: During follow-up after high
      dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to
      below normal in approximately one third of patients. However, in over half of
      these patients the LVEF subsequently recovered to the normal range, and the
      incidence of clinically evident chronic cardiac failure was low. Further follow
      up is required to assess the long-term safety. A randomized comparison with
      standard-dose anthracycline-based chemotherapy is needed to determine whether
      this regimen is associated with an increased risk of clinical cardiac toxicity.

PMID- 10076723
TI  - Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is
      effective in pretreated low-grade non-Hodgkin's lymphoma.
AB  - PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non
      Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances
      the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity
      of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in
      patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five
      adults with pretreated advanced-stage low-grade NHL were treated with three-day
      courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and
      dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS:
      Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR.
      Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients
      remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without
      further treatment after 12, 17 and 18 months. Myelosuppression was the most
      prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir
      < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter)
      occurred in only 10% and 16% of courses, respectively, slow granulocyte or
      platelet count recovery caused delay of 40% of the courses. Nine patients (36%)
      required discontinuation of therapy because of persistent granulocytopenia and/or
      thrombocytopenia: three after one course, three after 2-4 courses, and three
      after five courses. Thirteen infectious episodes in 11 patients complicated 11%
      of courses. Two of 10 patients monitored for the circulating EBV load showed
      increased viral load. One of these developed aggressive lymphoma. CD4+
      lymphocytes declined from a pre-therapy median value of 425/microliter to
      141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare
      and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and
      dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may
      broaden the range of therapeutic options in the salvage treatment of these
      patients. The main toxicity of this combination is prolonged myelosuppression
      that may cause treatment delay or withdrawal. The benefit of adding granulocyte
      colony-stimulating factor, particularly in patients with poor marrow reserve,
      needs to be investigated.

PMID- 10076724
TI  - Is primary CNS lymphoma really becoming more common? A population-based study of
      incidence, clinicopathological features and outcomes in Alberta from 1975 to
      1996.
AB  - BACKGROUND: The incidence of primary CNS lymphoma (PCNSL) is believed to be
      increasing in immunocompetent patients but this may not be universally true. The
      objective of this study was to determine in a population if the incidence of
      PCNSL is increasing, if the histologic subtypes are changing, and to describe the
      clinicopathologic and outcome characteristics of PCNSL. PATIENTS AND METHODS: We
      identified all Alberta residents with a histologic diagnosis of PCNSL from 1
      January 1975 to 31 December 1996 using the Alberta Cancer Registry. Annual age
      standardized incidence rates (ASIR), clinicopathologic and outcome
      characteristics were determined. RESULTS: There were 50 immunocompetent PCNSL
      patients; the median age was 64 and 30 were male. Their median survival was 10.15
      months. Histology was available for review in 37 (74%) patients: 19 (51%) were
      diffuse large cell, 16 (43%) were immunoblastic and 2 (5%) were unclassifiable
      malignant lymphomas. The ASIR ranged from 0.178-1.631/10(6) and no change in ASIR
      was found (test for trend, P = 0.26) for gender or age. The ASIR of malignant
      gliomas did not change either but increased for all other non-Hodgkin's lymphoma
      (94.95-138.7610(6); test for trend, P = 0.0001) The number of brain biopsies
      increased from 1979-1985 (test for trend, P < 0.0001) but remained stable from
      1986-1996 (test for trend, P = 0.99). CONCLUSIONS: Unlike several other
      populations, PCNSL is not becoming significantly more common in Alberta. If this
      difference is real (i.e., not due to differences in cancer registry coding
      practices etc.) comparisons between Albertans and other populations in whom the
      incidence is rising may provide clues regarding the etiology of PCNSL.

PMID- 10076725
TI  - Reduced health-related quality of life among Hodgkin's disease survivors: a
      comparative study with general population norms.
AB  - BACKGROUND: Late complications after curative treatment of Hodgkin's disease are
      of special relevance because most of the cured are young adults. The aims of the
      present study were: (1) to compare health-related quality of life (HRQOL) in
      Hodgkin's disease (HD) survivors with normative data from the general Norwegian
      population and (2) to examine the relations between disease/treatment
      characteristics and HRQOL in the HD survivors. PATIENTS AND METHODS: 459 HD
      survivors aged 19-74 years (mean 44.0, SD 11.8) treated at the Norwegian Radium
      Hospital 1971-1991 were approached in 1994 and compared to norms from 2214
      subjects approached in 1996. The norms are representative of the general
      Norwegian population. HRQOL was assessed by the Short Form 36 (SF-36), which
      measures HRQOL in eight separate scales (0 = worst health state, 100 = best
      health state). RESULTS: The HD survivors had lower scores than the normal
      controls on all scales after adjustment for age, gender and educational levels.
      Statistically significant differences (P < 0.01) were found in general health
      (10.4), physical functioning (6.1), role limitations (physical, 9.3), physical
      functioning (3.6) and in vitality (4.7). Patients with disease stage IB-IIB had
      the lowest scores on all scales. The differences in relation to stage/substage
      reached statistical significance (P < 0.01) in physical functioning and in role
      limitations (physical). Time since diagnosis, types of primary treatment or
      having relapsed were not associated with statistically significant differences in
      HRQOL. CONCLUSION: Long-term HD survivors have poorer HRQOL, primarily in
      physical health, than the general Norwegian population.

PMID- 10076726
TI  - Bone marrow scintigraphy using technetium-99m antigranulocyte antibody in
      malignant lymphomas.
AB  - BACKGROUND: The purpose of this study was to elucidate the clinical reliability
      of immunoscintigraphy (IS) to detect infiltration of the bone marrow in patients
      with malignant lymphoma. PATIENTS AND METHODS: Whole body IS was performed in 103
      patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) using Tc-99m
      labelled anti-NCA-95 which allows visualization of the granulopoietic bone
      marrow. Of these, 52% were studied prior to any therapy. Findings were compared
      to posterior iliac crest biopsy as well as MRI and/or follow-up examination.
      Criteria of marrow infiltration were a positive biopsy, positive follow-up, or
      positive results of MRI. RESULTS: Comparison of IS and biospy revealed concordant
      findings in 69 and discordant findings in 34 of 103 patients. Of the 34 patients
      with discordant results, IS showed lesions suspicious of bone marrow infiltration
      in 29 patients despite normal biopsy findings. When follow-up and additional
      examinations were taken into consideration, 10 patients remained with probably
      false positive and five with false negative IS findings. IS proved to be highly
      sensitive and specific in patients with HD (100% and 84%, respectively) and high
      grade NHL (93% and 84%, respectively). Moderate sensitivity (60%) was found in
      low-grade NHL. This was possibly due to false negative IS in three to five
      patients with chemotherapy in contrast to one of five false negative results in
      patients without chemotherapy. CONCLUSION: Bone marrow scintigraphy using
      antigranulocyte antibodies is highly sensitive in HD and high-grade NHL. Positive
      findings in IS subsequent to a negative biopsy should be followed by guided re
      biopsy or MRI.

PMID- 10076727
TI  - Psychosocial impact of genetic testing in familial medullary-thyroid carcinoma: a
      multicentric pilot-evaluation.
AB  - BACKGROUND: Many crucial problems are associated with the diagnosis of inherited
      cancer susceptibility. One of the most important is related to the psychosocial
      consequences of the knowledge by the patients and their relatives of their own
      genetical status. Little data are available in the literature, mainly from
      studies including small numbers of selected and motivated patients. PATIENTS AND
      METHODS: From January till December 1997, we studied the psychometric and quality
      of life parameters of 77 subjects followed in two French specialized centers.
      These subjects had been treated for either sporadic or familial or were at risk
      for medullary thyroid carcinoma. All patients had previously attended genetic
      counselling with detection of germline Ret-mutations, were informed on their own
      genetic risk, had good short-term prognosis and performance status and did not
      receive recent cancer treatment. Each patient was invited to answer two
      questionnaires, the hospital anxiety and depression scale (HADS) and the
      subjective quality of life profile (SQLP). RESULTS: We report herein the
      descriptive results of this study (HADS and SQLP scores and distributions) and
      describe the individual clinical covariates that might explain the observed
      differences between subgroups of individuals. Although psychometric scores
      appeared similar in these subgroups, quality of life scores were lower in Ret
      mutation carriers. Genetically-predisposed patients were less satisfied and
      expressed more expectations for favourable change in their quality of life.
      CONCLUSION: This finding suggests a high level of frustration and latent
      unsatisfaction related either to the management of the genetic information given
      by the clinicians and its psychosocial consequences or simply to the knowledge of
      the genetic risk of cancer. Further studies on the individual consequences of
      genetic testing, information delivery and when necessary psychotherapeutic
      interventions, are needed to insure the quality of presymptomatic genetic testing
      in this field of oncology.

PMID- 10076728
TI  - The potential of plantinum-DNA adduct determination in ex vivo treated tumor
      fragments for the prediction of sensitivity to cisplatin chemotherapy.
AB  - BACKGROUND: Response to cisplatin-therapy is assumed to be related to the
      formation of platinum (Pt)-DNA adducts. Measurement of these adducts prior to
      therapy could be of value to improve cisplatin based cancer therapy. MATERIALS
      AND METHODS: We determined Pt-GG and Pt-AG adduct levels by use of 32P
      postlabeling after ex vivo cisplatin treatment of fragments of head and neck
      squamous cell carcinoma (HNSCC) xenografts (five lines), and of tumor biopsies
      from patients with HNSCC (n = 8) and testicular cancer (n = 8). RESULTS: Adduct
      levels in fragments (3 x 3 x 3 mm) exposed to 10 to 80 microM cisplatin for one
      hour, showed positive correlations with the in vivo response to cisplatin
      treatment (P < 0.05), as well as with the xenograft adduct levels observed after
      in vivo cisplatin treatment (P < 0.02). After an additional five-hour drug-free
      incubation period the correlations were absent. When patient tumor fragments were
      exposed ex vivo to 80 microM cisplatin for one hour, adduct levels were similar
      in HNSCC and testicular cancer. Persistence of adducts was observed for
      testicular cancer in the additional drug-free period. The adduct levels in the
      samples of two HNSCC patients who received cisplatin chemotherapy were in line
      with the hypothesis that higher adduct levels are associated with a better
      response. CONCLUSION: Our preliminary results show that analysis of DNA adducts
      following ex vivo drug treatment is a feasible approach towards a predictive
      assay, which warrants further investigation.

PMID- 10076729
TI  - Chemotherapy for advanced pancreatic cancer: it may no longer be ignored.
AB  - Two case histories are reported here in which a chemotherapeutic approach
      improved the clinical conditions of patients with advanced pancreatic cancer.
      Until recently, chemotherapy was considered ineffective in pancreatic cancer, and
      most oncologists treated these patients with best-supportive-care only.
      Enthusiasm for systemic therapy of advanced pancreatic cancer is again growing,
      spurred by the advent of new drugs and new treatment endpoints such as life
      quality and symptom palliation. Gemcitabine, the most intensively-investigated
      new drug in pancreatic cancer, has shown an advantage in both survival and
      clinical benefit over that of 5-fluorouracil (5-FU). Other new drugs such as
      taxanes have shown interesting levels of activity, and are deserving of further
      evaluation. Although these results are far from conclusive and are only partially
      satisfactory, they represent a significant step forward in the treatment of
      advanced pancreatic cancer.

PMID- 10076730
TI  - Up-regulated pyrimidine nucleoside phosphorylase in breast carcinoma correlates
      with lymph node metastasis.
AB  - BACKGROUND: The clinical significance of pyrimidine nucleoside phosphorylase
      (PyNPase) activity in breast carcinomas has never been determined. MATERIALS AND
      METHODS: In 41 cases of breast carcinoma, the enzyme activity of PyNPase was
      determined by the high performance liquid chromatography (HPLC) assay and its
      value was analyzed with clinicopathologic variables. The expression level of mRNA
      was examined by the semi-quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay and compared with the enzyme activity. RESULTS: The
      higher activity of PyNPase was significantly correlated not only with the
      presence of vascular permeation (P = 0.02) but of lymph node metastasis (P =
      0.02). The mRNA expression correlated well with the enzyme activity (r = 0.74, P
      < 0.01). A multivariate analysis disclosed the PyNPase factor to be associated
      with lymph node metastasis. In addition, 17 (41%) showed positive staining only
      in the tumor stromal cells and 18 (44%) cases showed positive staining in both
      the tumor stromal cells and the carcinoma cells by immunohistochemical study.
      CONCLUSIONS: These findings suggest that PyNPase activity is a new marker
      predicting the malignant potential of breast carcinomas, especially with respect
      to lymph node metastasis, and that the RT-PCR assay is a more useful method than
      direct evaluation of PyNPase activity.

PMID- 10076731
TI  - Treatment of mantle-cell lymphomas with intermittent two-hour infusion of
      cladribine as first-line therapy or in first relapse.
AB  - PURPOSE: Cladribine (2-chlorodeoxyadenosine, 2-CdA) has been reported to be
      effective in the treatment of low-grade lymphomas. The objective of this
      multicenter study was to evaluate the activity of cladribine in mantle-cell
      lymphomas as first-line therapy or in first relapse using an intermittent two
      hour infusion of cladribine. PATIENTS AND METHODS: A total of 47 courses, or an
      average of four courses per patient, were administered to 12 patients (seven
      untreated, five relapsed) with 5 mg/m2 cladribine given as an intermittent two
      hour infusion over five consecutive days for a maximum of six cycles every four
      weeks. RESULTS: Cladribine showed activity in patients with mantle-cell
      lymphomas, achieving a response rate of 58% (95% confidence interval (95% CI):
      28%-85%). Myelosuppression was the major toxicity with 17% of grade 3 and 4
      neutropenia. Thrombocytopenia was rare with only 2% of grade 3 and 4. CONCLUSION:
      These results demonstrate single-agent activity of cladribine in mantle-cell
      lymphomas using the intermittent two-hour infusion dosage regimen. To further
      improve treatment results, cladribine should be combined with other agents active
      in mantle-cell lymphomas.

PMID- 10076732
TI  - Docetaxel and cisplatin: an active regimen in patients with locally advanced,
      recurrent or metastatic squamous cell carcinoma of the head and neck. Results of
      a phase II study of the EORTC Early Clinical Studies Group.
AB  - BACKGROUND: Docetaxel and cisplatin are among the most active antitumor agents in
      head and neck cancer, and phase I studies found the combination of the two drugs
      to be feasible. The EORTC ECSG performed a multicenter phase II study in patients
      with locally advanced, recurrent or metastatic squamous cell carcinoma of the
      head and neck to evaluate the antitumor efficacy and toxicity of this
      combination. PATIENTS AND METHODS: Eligibility criteria included written informed
      consent, a WHO performance status < 2, life expectancy of > 12 weeks, and
      adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with
      cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were
      ineligible if pretreated with taxoids, had CNS involvement, concurrent
      malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted
      of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2
      (three-hour i.v. infusion), repeated every three weeks. Supportive care included
      hydration, 5HT3-antagonists, and corticosteroids. RESULTS: Forty-four patients
      (median age 55 years, range 35-76) entered the trial; 41 patients were eligible,
      164 cycles of treatment were evaluable for toxicity, and 31 patients for
      response. Fourteen patients had undergone prior surgery, 15 had received
      radiotherapy, and five had had chemotherapy. A median number of four treatment
      cycles (range 1-6) was given. Hematologic and non-hematologic toxicities were
      common, but hypersensitivity reactions and fluid retention were very infrequent
      due to corticosteroid prophylaxis. Four patients were taken off the study due to
      toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible
      patients, objective responses as confirmed by independent review included six
      complete remissions and 16 partial remissions, resulting in an overall response
      rate of 53.7% (95% confidence interval: 37.4%-69.3%). Responses occurred in
      locally advanced, recurrent and metastatic disease, both in pre- and non
      pretreated patients. Of 22 evaluable, non-pretreated patients with locally
      advanced or metastatic disease, five achieved complete responses, and 14 partial
      responses. Observed among nine evaluable pretreated patients with locally
      advanced or metastatic head and neck cancer were one complete response and two
      partial responses. CONCLUSION: The combination of docetaxel and cisplatin is
      feasible and active in locally advanced, recurrent, and metastatic squamous cell
      carcinoma of the head and neck.

PMID- 10076733
TI  - Treatment of soft-tissue sarcomas: high-dose ifosfamide or combination of
      ifosfamide and etoposide?

PMID- 10076734
TI  - Oral ipriflavone (7-isopropoxy-isoflavone) treatment for elderly patients with
      resistant acute leukemias.

PMID- 10076735
TI  - Telomerase or telomersyn?

PMID- 10076736
TI  - Millennium--fantasy, furor, and fact.

PMID- 10076737
TI  - Does stress cause posttraumatic stress disorder?

PMID- 10076738
TI  - Individual differences in posttraumatic distress: problems with the DSM-IV model.
AB  - OBJECTIVE: To evaluate the evidence concerning the role of threatening life
      events in accounting for clinically significant posttraumatic stress responses.
      METHOD: Research was examined to review the epidemiology, evidence of dose
      response relations, and individual difference factors in accounting for
      variations in conditions, including posttraumatic stress disorder, after exposure
      to threatening events. RESULTS: The evidence is significantly discrepant from the
      clinical Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) model.
      Greater distress arises from individual differences than from event
      characteristics. Important individual differences that interact with threat
      exposures include trait negative affectivity (neuroticism); beliefs about
      emotions, the self, the world, and the sources and consequences of danger; and
      prevent acts, disorders, and intelligence. Reasons for the discrepancies between
      the evidence and the current model of posttraumatic distress are proposed.
      CONCLUSION: In accounting for responses to threatening life events, the
      relatively minor contribution of event qualities compared with individual
      differences has significant treatment implications. Treatment approaches assuming
      that toxic event exposure creates a posttraumatic disorder fail to consider
      individual differences that could improve treatment efficacy.

PMID- 10076739
TI  - Biological factors associated with susceptibility to posttraumatic stress
      disorder.
AB  - Because only a proportion of persons exposed to traumatic events develop
      posttraumatic stress disorder (PTSD), it has become important to elucidate the
      factors that increase the risk for the development of PTSD following trauma
      exposure as well as the factors that might serve to protect individuals from
      developing this condition. Putative risk factors for PTSD may describe the index
      traumatic event or characteristics of persons who experience those events. Recent
      data have implicated biological and familial risk factors for PTSD. For example,
      our recent studies have demonstrated an increased prevalence of PTSD in the adult
      children of Holocaust survivors, even though these children, as a group, do not
      report a greater exposure to life-threatening (Diagnostic and Statistical Manual
      of Mental Disorders [DSM-IV] Criterion A) events. These studies are reviewed. It
      is difficult to know to what extent the increased vulnerability to PTSD in family
      members of trauma survivors is related to biological or genetic phenomena, as
      opposed to experiential ones, because of the large degree of shared environment
      in families. In particular, at-risk family members, such as children, may be more
      vulnerable to PTSD as a result of witnessing the extreme suffering of a parent
      with chronic PTSD rather than because of inherited genes. But even if the
      diathesis for PTSD were somehow "biologically transmitted" to children of trauma
      survivors, the diathesis is still a consequence of the traumatic stress in the
      parent. Thus, even the most biological of explanations for vulnerability must at
      some point deal with the fact that a traumatic event has occurred.

PMID- 10076740
TI  - The self-mutilative nature of severe onychophagia: a comparison with self
      cutting.
AB  - OBJECTIVE: To investigate the psychophysiological pattern associated with severe
      and mild onychophagia, and to compare this pattern with that demonstrated by
      previous research on self-cutting. METHOD: Comparisons between the
      psychophysiological responses accompanying 3 behaviours were made using a guided
      imagery methodology. Imagery of nail-related, skin-cutting, and neutral events
      were presented in 4 stages. RESULTS: Experiment I distinguished participants
      exhibiting severe and mild onychophagia by the severity and frequency of nail
      biting and by the pattern of psychophysiological response across the stages.
      Experiment II indicated that the change in psychophysiological arousal
      accompanying severe onychophagia was not as dramatic as that demonstrated for
      skin-cutting. The behaviour seems to be less effective in reducing tension.
      CONCLUSION: Severe onychophagia appears to manage the level of tension
      experienced by an individual, instead of dramatically reducing it in times of
      crisis. Such a process is consistent with that demonstrated in individuals with
      obsessive-compulsive disorder.

PMID- 10076741
TI  - [Evaluation of potential community resources for mental health].
AB  - OBJECTIVES: Within the framework of the mental health services regional
      organization, the objectives are to describe and assess a day-care type
      alternative, informal mental health care service model. METHOD: One hundred and
      twenty-nine subjects were studied in a stratified sample from 3 community
      organizations in a mostly urban subregion in Quebec. The data were collected in
      several steps with 3 types of respondents: the user, the clinical team, and the
      community organization. In addition to the GAS and MRSS scales, a questionnaire
      was used to establish a sociodemographic profile and a health profile (diagnosis,
      medication, hospitalizations, outpatient follow-up). The EDBES was also used to
      assess the need (or lack thereof) for 25 mental health care services and their
      use during the last month. RESULTS: Users are mostly individuals with severe and
      persistent disorders. Community organizations meet 40% of their needs.
      CONCLUSION: The 3 organizations play a key role in mental health care services.
      Their contribution, however, could be enhanced by increasing subsidies; this
      would allow for permanent staff and longer office hours and would improve
      coordination and cooperation with clinical treatment teams.

PMID- 10076742
TI  - Paternal filicide: a study of 10 men.
AB  - OBJECTIVE: To describe the psychiatric and sociodemographic profiles of 10 men
      who killed 1 or more of their children. METHOD: Data were gathered from
      psychiatric, psychological, and criminological assessments found in the files of
      10 filicidal men hospitalized at the Institut Philippe Pinel de Montreal between
      1982 and 1994. RESULTS: Many situational factors were present during the period
      preceding the offence (such as the possibility of a separation or financial
      problems). Most of these homicides have been classified as pathological
      filicides. At the time of the offence, the most frequent diagnoses were mood
      disorders. Eight subjects had personality disorders, one-half of which were
      borderline personality disorders. Four men had psychotic symptoms at the time of
      the offence. Six of the 10 men also killed or attempted to kill their spouses.
      CONCLUSION: Many factors are involved in the dynamics of a filicidal situation.
      It is therefore difficult to identify specific warning signals for the prevention
      of this type of homicide. However, mental health professionals and the general
      population must be made aware of the importance of early assessment of possible
      filicidal tendencies when a man verbalizes delusional ideas about his child
      and/or if he manifests disorganized and bizarre behaviour.

PMID- 10076743
TI  - Cognitive-behaviour therapy and medication in the treatment of obsessive
      compulsive disorder: a controlled study.
AB  - OBJECTIVE: To evaluate the effect of combining cognitive-behaviour therapy (CBT)
      and medication in the treatment of obsessive-compulsive disorder (OCD). METHOD:
      Twenty-nine subjects diagnosed with OCD according to Diagnostic and Statistical
      Manual of Mental Disorders (DSM-III-R) criteria were recruited through the
      Anxiety Clinic of Louis-H Lafontaine Hospital. They were evaluated at baseline
      and after treatment on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) by a
      psychiatrist who was blind to treatment modality. Subjects rated their degree of
      resistance to their rituals and the strength of their obsessional beliefs.
      Subjects then received 1 of 4 treatments: medication and CBT simultaneously (n =
      9), CBT only (n = 6), medication while on a wait-list for CBT (n = 6), or no
      treatment while on a wait-list for CBT (n = 5). RESULTS: Multivariate analysis
      revealed that Y-BOCS scores and clinical ratings significantly improved
      posttreatment in all groups except the nontreatment wait-list control group.
      Subjects in the 2 active treatment groups receiving CBT showed reduced strength
      in their obsessional beliefs. The subsequent administration of CBT to those
      groups on the wait-list also decreased the strength of their primary obsessional
      beliefs and beliefs about the consequences of not performing the rituals.
      CONCLUSIONS: Our results suggest that either CBT or medication alone is more
      effective than no treatment. The combination of CBT and medication seems to
      potentiate treatment efficacy, and we found it more clinically beneficial to
      introduce CBT after a period of medication rather than to start both therapies
      simultaneously.

PMID- 10076744
TI  - Psychoanalytic contributions to the study of gender issues.
AB  - OBJECTIVE: To explore the issue of gender development and its applications and
      implications with respect to dynamic psychiatry. METHOD: Gender study is
      approached in this paper as a continually evolving process of thinking about male
      and female attributes, similarities, and differences. The paper reviews a
      specific thematic area of the extensive literature on the subject. RESULTS:
      Gendered psychosexual development and identity construction are intertwined and
      determined by multibiopsychosocial factors. Freud's theory on femininity is
      briefly reviewed from the perspective of new theoretical developments.
      CONCLUSIONS: The paper highlights the fact that gender is becoming a useful
      conceptual tool in clinical practice, teaching, and neurosciences.

PMID- 10076745
TI  - Emotional adaptation of children undergoing bone marrow transplantation.
AB  - OBJECTIVE: To examine stress reactions and psychic adaptation of children aged 8
      12 years in single-room treatment under isolation conditions after bone marrow
      transplantation (BMT). METHODS: The prospective longitudinal study included free
      diagnostic interviews and a large test battery. We used a mixture of projective
      tests questionnaires and an intelligence test (the German version of the revised
      Wechsler Intelligence Scale for Children) to evaluate different adaptation
      processes. RESULTS: The questionnaires clearly showed children's strong
      tendencies to adapt to the situation and to normalize their behaviour under
      isolation conditions. In contrast, the psychoanalytic interview and the
      projective tests demonstrated a very differentiated emotional adjustment: Before
      transplantation, coming to terms with the life-threatening situation was
      deferred. After transplantation, very intensive emotional examination of the
      situation and superficial adaptation (protective denial) were observed.
      CONCLUSIONS: It is very important to intensify the child's and the family's
      psychosocial support before admitting the child for hospital treatment. Family
      conflicts and neurotic developments should be regarded as risk factors for marked
      and potentially dangerous stress reactions.

PMID- 10076746
TI  - A new factor in youth suicide: the relative age effect.
AB  - OBJECTIVE: To determine whether youth in Alberta who had completed suicide were
      more likely to be younger than their classmates on entering grade 1 (that is,
      showed a relative age effect). METHOD: Records were obtained for all deaths by
      suicide by individuals under the age of 20 years in Alberta during the years 1979
      1992. The relative age of each of these persons was determined by comparing his
      or her month of birth to the birth months of the appropriate school-grade cohort.
      RESULTS: A disproportionate number of the subjects were born in the second half
      of the "school eligibility year," indicating a higher probability that those who
      completed suicide were younger than their classmates. CONCLUSIONS: Previous
      research indicates that relative age is strongly related to school performance
      and success in sports. The present study demonstrates that the relative age
      effect is also a factor in youth suicide. It is suggested that the higher
      incidence of youth suicide in the group of relatively younger school children may
      have resulted from poorer school performance, which in turn led to lowered
      confidence and self esteem. Past research suggests that these conditions may
      predispose children to hopelessness and depression, which are often thought to be
      essential components of suicide. Research aimed at neutralizing the negative
      effects of relative age should have important personal and social consequences.

PMID- 10076747
TI  - Creativity, hyperesthesia, and mental illness.

PMID- 10076748
TI  - Association of Diogenes syndrome with a compulsive disorder.

PMID- 10076749
TI  - Hypercortisolemia and post-ECT confusion.

PMID- 10076750
TI  - Level of schooling and obsessive-compulsive disorder.

PMID- 10076751
TI  - Re: Sexual recidivism in sex offenders.

PMID- 10076752
TI  - Feasibility of client reports to measure treatment outcome in schizophrenia.

PMID- 10076753
TI  - Re: Selective serotonin reuptake inhibitor discontinuation syndrome: putative
      mechanisms and prevention strategies.

PMID- 10076754
TI  - Diaphragmatic denervation in intensive care unit patients.
AB  - The causes of prolonged requirement for mechanical ventilation in the intensive
      care unit (ICU) are currently a subject of investigation. Critical illness
      polyneuropathy (CIP), an axonal polyneuropathy that frequently occurs with
      prolonged sepsis and multi-organ failure, has been cited as a frequent cause of
      difficulty with weaning from a ventilator. The relative contribution of
      diaphragmatic denervation in ICU patients with and without CIP has not been
      definitively determined. We reviewed 102 ventilator dependent intensive care unit
      (ICU) patients. Critical illness polyneuropathy (CIP) was diagnosed based upon
      electrodiagnostic criteria. Electrodiagnostic studies included diaphragmatic
      needle electromyography (EMG) to evaluate for diaphragmatic denervation. The
      medical charts of the patients with diaphragmatic denervation were reviewed for
      etiologies other than CIP for the diaphragmatic denervation. Our results suggest:
      1) Respiratory impairment in ICU patients may often be unrelated to either CIP or
      diaphragmatic denervation; 2) Only about half of ventilator dependent CIP
      patients have diaphragmatic denervation; 3) Diaphragmatic denervation in ICU
      patients frequently may be attributable to causes other than CIP.

PMID- 10076755
TI  - F-wave amplitude.
AB  - To determine the diagnostic efficacy of F-wave amplitude and F/M-ratio
      measurements in routine electrodiagnostic examinations, normal values were
      established for the ulnar nerve and systematically applied to a group of patients
      with various nosological entities (Mononeuropathies at the elbow, radiculopathies
      of C8, polyneuropathies, anterior horn cell disorders, plexopathies,
      syringomyelias, others). As a result, F/M-ratio can distinguish between the
      various pathological conditions (P = 0.02). Patients with radiculopathy and
      accompanying myelopathy were identified by increased F/M-ratio. It is concluded
      that F-wave amplitude analysis can give hints for additional central pathology in
      the individual case.

PMID- 10076756
TI  - Joint amplitude and frequency analysis of tremor activity.
AB  - Clinical tremor analysis mostly is used for the measurement of tremor frequency.
      The analysis is based on short segments of EMG recordings and on clinical ratings
      of tremor intensity. Accelerometry appears to have some practical advantages. The
      present study was concerned with the development of a methodology for assessing
      tremor activity using the three parameters, frequency (Hz), amplitude (g), and
      occurrence of tremor (in per cent of time). These parameters were derived from
      joint amplitude frequency analysis of the calibrated accelerometer raw signal and
      from appropriate decision rules. This methodology was used in connection with 27
      patients with Parkinson's disease, to investigate the aforesaid parameters of
      tremor activity. Postural tremor had a higher occurrence time (right-hand only)
      and higher frequency (left-hand only) than resting tremor, however, the average
      amplitudes did not differ. The correlations between right-hand and left-hand
      measures were higher during postural tremor test. Frequency was not correlated to
      amplitude or occurrence time, however, moderate correlations did exist between
      amplitude and occurrence time. In addition to the assessment of tremor activity,
      multi-channel accelerometry may be used for the detection of posture and motion.
      Further applications of this methodology, for example, in 24 hr ambulatory
      monitoring of tremor, are discussed.

PMID- 10076757
TI  - Modulation of the soleus H reflex with different velocities of passive movement
      of the arm.
AB  - Modulation of the gain of the soleus H reflex pathway produced by passive
      movement of the elbow joint was investigated and compared to that produced by
      passively maintained displacement of the elbow joint position. Little modulation
      of the gain of the soleus H reflex pathway was observed during passive
      displacement of the elbow joint position. In contrast, passive movement of the
      elbow joint facilitated the gain of the soleus H reflex amplitude and the degree
      of modulation was large as the velocity increased. The degree of the facilitatory
      effect upon passive movement of the upper extremity ipsilateral to the leg under
      test was larger than that obtained upon passive movement of the upper extremity
      contralateral to the leg under test. The modulation may be caused by discharge at
      the primary endings of the spindles in the upper extremity which is likely to
      excite propriospinal interneurons connecting to motor neurons of the lower
      extremity.

PMID- 10076758
TI  - Spinal motoneuron function in lower motor neuron disease: normal
      corticomotoneuronal and peripheral Ia EPSPs in patients with spinal muscular
      atrophy.
AB  - Responses of single tibialis anterior motor units to transcranial magnetic
      stimulation and to a synchronized Ia volley evoked by peripheral electrical nerve
      stimulation were obtained in patients with distal spinal muscular atrophy and
      compared to normal controls. Estimations of excitatory postsynaptic potential
      (EPSPs) by cross-correlations revealed no difference in rise time of EPSPs for
      both groups of subjects despite considerable changes in macro-EMG parameters of
      the motor units studied in patients with spinal muscular atrophy (SMA). The
      results indicate that voluntarily activated spinal motoneurons in SMA are capable
      of normal excitatory responses to transcranial magnetic as well as peripheral Ia
      stimulation.

PMID- 10076759
TI  - Chronic steadily progressive central and peripheral predominantly motor
      demyelination, involving the cranial nerves, responsive to immunoglobulins.
AB  - The association of central and peripheral demyelination was reported previously.
      Most of the cases refer to central chronic relapsing demyelination with clinical
      criteria for multiple sclerosis associated with later signs of peripheral nerve
      involvement. Other authors, described central lesions in patients with chronic
      inflammatory demyelinating polyneuropathy and in Guillain-Barre syndrome, as a
      seldom occurrence. We report a patient in which a chronic steadily progressive
      central and peripheral predominantly motor nervous system demyelination,
      involving the cranial nerves, was identified. The patient improved after
      intravenous immunoglobulin suggesting an immune-mediated mechanism. To our
      knowledge this presentation was not described before.

PMID- 10076760
TI  - Hypertriglyceridemia may cause a subclinical peripheral neuropathy.
AB  - Recently few patients with a painful neuropathy, attributed to extremely high
      triglyceride levels, were reported. In a prospective study, we evaluated 16
      patients with marked hypertriglyceridemia without other causes of neuropathy,
      using nerve conduction and autonomic function tests. Six subjects (37%) showed
      mild signs of an asymptomatic motor and/or sensory and/or autonomic axonal
      polyneuropathy. The study demonstrates, that hypertriglyceridemia may be
      associated with a mild axonal polyneuropathy, usually subclinical, in
      significantly more patients than previously considered.

PMID- 10076761
TI  - Neuromuscular activation and RPE in the quadriceps at low and high isometric
      intensities.
AB  - INTRODUCTION: The purpose of this study was to examine neuromuscular activation
      and ratings of perceived exertion (RPE) at 10% and 80% quadriceps MVC in healthy
      males. METHODS: Seventeen college-aged volunteers (mean age = 22.6 years, mean
      height = 178.9 cm, mean weight = 78.8 kg) were assessed for isometric EMG
      activity of the vastus medialis (VM) and vastus lateralis (VL) at 10% and 80%
      MVC, and RPE at 80% MVC. Perceived exertion was measured with a modified category
      ratio scale (CR-10) and was anchored with 1 high and 1 low anchor. Raw EMG
      signals were sampled via telemetry (rate = 1,000 Hz) and integrated (3 sec) for
      each contraction for each muscle (bandpass = 16-500 Hz, CMRR = 130 dB). A one
      sample t-test was performed for each variable and 95% confidence intervals were
      calculated. RESULTS: Means and CI for each variable are as follows: 10% MVC VM
      IEMG (t16 = 5.05, p < 0.001, .95 CI = 3.11 +/- 1.3), 80% MVC VM IEMG (t16 =
      22.51, p < 0.001, .95 CI = 73.2 +/- 6.89), 10% MVC VL IEMG (t16 = 8.10, p <
      0.001, .95 CI = 9.41 +/- 2.47), 80% MVC VL IEMG (t16 = 39.56, p < 0.001, .95 CI =
      87.32 +/- 4.68), and 80% MVC RPE (t16 = 11.85, p < 0.001, .95 CI = 5.24 +/-
      0.93). DISCUSSION: The major findings illustrate an apparent underestimation of
      RPE at 80% MVC for the quadriceps. Neuromuscular activation appears to be lower
      than the expected force output at both intensities for the VM while VL activation
      corresponded closely at 10% MVC and was higher at 80% MVC.

PMID- 10076762
TI  - Neurophysiology of orthostatic tremor. Influence of transcranial magnetic
      stimulation.
AB  - A 74-year-old patient suffers from painful muscle cramps when he stands since 30
      years. He has no visible tremor but 16 Hz burst activity on EMG, indicating
      orthostatic tremor. Previous diagnosis was hysteria, stiff person syndrome or
      dystonia. This shows that EMG during standing should be part of the examination
      of patients with stiff muscles or muscle cramps. Tremor was not strictly
      orthostatic. It appeared in back muscles while sitting, when the patient
      supported a weight with outstretched arms. Phase between muscles differed between
      normal standing and standing on heels. Subthreshold transcranial magnetic
      stimulation modulated timing of the tremor bursts and inhibited them at higher
      intensity stimulation.

PMID- 10076763
TI  - Experimental stationary potential recorded with using spine and skull model.
AB  - This study aims at investigating experimentally the structural effects of various
      shapes of volume conductors, which are surrounded by an insulated skull and
      spinal canal model, on nerve action potentials (NAP). NAP were recorded through
      volume conductors inside and outside a model. We noted stationary potentials
      emerged at where the volume conductor made structural transitions. These results
      were analyzed using the field diagram of isopotential curves. The diagrams of the
      electrical field demonstrated that the stationary potentials arise owing to
      abrupt disequilibrium of the electrical field brought about by the change of the
      volume conductor surrounded by the insulated model.

PMID- 10076764
TI  - Sensory nerve conduction velocity is inversely related to axonal length.
AB  - It was found that the axonal length was inversely related to motor conduction
      velocity (CV). However, it is not clear that sensory CV is inversely related to
      axonal length. The nerve lengths of the median sensory fascicles from the C6 and
      C7 intervertebral foramen to the digital branches of the thumb and middle finger
      were compared in ten cadavers. Sixty healthy subjects (24 men, 36 women; mean age
      35, range 24-54 years) had median sensory CV testing. The median sensory nerve
      action potentials were obtained antidromically in the thumb and middle finger
      with wrist and elbow. The CVs across the forearm for the thumb and the middle
      finger fascicles were then calculated. It was found that the nerve length of C7
      was longer than C6 with a difference of 3.6 +/- 0.6 cm. The mean forearm CV for
      the median sensory axons innervating the middle finger (60.0 +/- 3.9 m/s) was
      slower than the CV for the median sensory axons innervating the thumb (61.4 +/-
      4.1 m/s,p = 0.0012). These results demonstrate that sensory CV is slowed by 3.9
      m/s per 10 cm of axon length. This study confirms that the inverse relation of CV
      and axonal length reported in motor axons also applies to the sensory nerves.

PMID- 10076765
TI  - From the histophotometer to the confocal microscope: the evolution of analytical
      microscopy.
AB  - With new ideas and with the aid of modern technology, novel microscopical and
      micro-analytical methods are practically implemented, as a fruit of the co
      operative effect of theoretical and experimental advances achieved in distinct
      fields. The results obtained in the development of new micro-analytical
      instruments and in their applications, increasingly help to solve many
      investigative problems in materials science and in biology. Among the oldest
      forms of analytical microscopy, some encountered histophotometers while, among
      the latest, some are working with confocal microscopes. Given by one that had the
      opportunity of attending to both of the developments, an overview encompassing
      these two instruments can hopefully serve to illustrate the progress of
      analytical microscopy, a discipline evolving during the second half of this
      century.

PMID- 10076766
TI  - Flow cytometric fluorescence lifetime analysis of DNA-binding probes.
AB  - A new dimension has been added to multiparameter flow cytometric analysis through
      the recent development of techniques for rapidly measuring the fluorescence
      lifetime of probes bound to single cells. The lifetime measurements are made by
      phase-sensitive detection techniques in a flow cytometer (FCM) that also analyzes
      fluorescence intensity and other optical properties of stained cells. These
      lifetime assays have potential for elucidating the microenvironment of the
      interaction of fluorochrome probes and subcellular target molecules. Alterations
      in the lifetime of DNA probes have been observed in cells in different phases of
      the cell cycle, in different cell types, in differentiating cells, and in
      apoptotic cells with damaged chromatin. Lifetime differences noted also for
      intercalating dyes bound to DNA and dsRNA, indicated modifications in the modes
      of binding and provide the potential for analyzing both corformational states and
      nucleic acid metabolism. Future developments in the technology will provide
      multiple lifetime assays and thereby allow for detection and quantitation of
      selected subcellular probe-complexes with different lifetime signatures. These
      novel assays will expand the applications for quantitative studies on the binding
      of various chemical agents to DNA and other molecular targets in cells, and
      further improve methods for rapid screening of chemotherapeutic agents or
      environmentally toxic compounds.

PMID- 10076767
TI  - How rational histochemistry produced order out of chaos in the "amorphous ground
      substance" (with a little help from biochemistry, biophysics etc.).
AB  - From an amorphous ground substance containing polymers of unknown composition
      arranged in no particular pattern we have in about 50 years arrived at a proposal
      where the very shape of the tissue and hence of the organism is determined by
      newly discovered structures, the shape modules, in the ground substance, which
      were demonstrated by histochemical techniques interpreted on rational biophysical
      and chemical principles.

PMID- 10076768
TI  - The everchanging advances in enzyme histochemistry, 1986-1996.
AB  - The principal developments in the field of enzyme histochemistry in the ten years
      since 1986 are reviewed briefly. They include the replacement of catalytic
      histochemistry by immunohistochemistry as the principal means of localising
      enzymes in situ, including isoenzymes and classes of enzymes that were not
      possible to visualize hitherto; the development of in situ hybridization and
      reverse transcriptase-polymerase chain techniques; and the quantification of
      enzyme distribution and kinetic parameters.

PMID- 10076769
TI  - Cytochemistry of the functional domains of the nucleus in normal and in
      pathologic conditions.
AB  - By means of ultrastructural cytochemistry significant advances have been made in
      understanding the functional roles of many nuclear domains. This review gives
      schematic information about the main nuclear domains involved in replication,
      transcription, processing and transport of the transcripts in normal and in
      pathologic conditions. Particular attention is paid to a functional domain that
      appears to be involved in signal transduction. Data are reported on the
      intranuclear specific localization of key elements of the polyphosphoinositide
      signal transduction system in different cell types including human osteosarcoma
      cell lines. Compared with the compartmentalization of the cytoplasm, the nucleus
      has long been considered as relatively unstructured. On the other hand,
      fundamental nuclear functions, such as DNA replication and RNA transcription, can
      be molecularly characterized also in cell-free systems, suggesting that
      supramolecular organization is not so strictly required as for other cell
      functions occurring within intact cytoplasmic organelles. Nevertheless, a
      stringent organization is required for packing about 200 cm of DNA in the about
      30 micron 3 of the nucleus. In the absence of membrane-delimited organelles, the
      nuclear organization is based on functional compartments, or domains, whose
      spatial localization involves the nuclear matrix, which shares many properties
      with the cytoskeleton. The nuclear domains are defined as structural
      compartments, not necessarily stable but dynamically variable, which perform
      specific metabolic functions through the partitioning of molecular complexes.
      Their identification has been made possible in the last few years by the
      development of specific nuclear probes for confocal and electron microscope
      immunocytochemistry. Therefore, the complex network of structures and enzymatic
      functions that make up the nucleus is in several cases yielding to molecular
      analysis, but a large part remains unknown (Strouboulis and Wolffe, 1996; Laemmli
      and Tjian, 1996). Rapid advances in understanding the functional role of the
      nuclear domains have been made recently: in particular, of the nuclear envelope,
      of the nucleolus, and of RNA splicing. In other cases, e.g. the precise
      localization of the nuclear domains involved in signal transduction, much remains
      to be clarified (Forbes and Johnson, 1997). It is conceivable that in the near
      future unexpected new nuclear domains will come to light and new nuclear
      functions may emerge, especially in field of post-transcriptional processing and
      transport of RNAs, and in the relationships between the nucleo-skeleton and
      enzymic fixed sites involved in replication, transcription and signal
      transduction. The aim of this review is to provide information about the
      morphological characteristics, the associated functions and the molecular
      composition of the main nuclear domains found to date. To simplify the
      exposition, the main data on each nuclear domain are reported in Tables, together
      with the principal references on the subject. Figures refer to original findings
      on some aspects of nuclear domain organization.

PMID- 10076770
TI  - Cytochemistry of neurotransmitters: from statical analysis to the understanding
      of dynamic processes.
AB  - In the past thirty years, cytochemical methods have allowed neuroscientists to
      identify and localize neuroactive molecules (neurotransmitters and
      neuropeptides), their receptors and their synthetic enzymes, and have advanced
      the understanding of many neuronal functions. Classic methods (histochemical and
      immunohistochemical techniques) have been used extensively to draw neurochemical
      maps in adult and developing nervous systems. As a consequence, many neuroactive
      molecules have become specific biochemical markers for neuronal systems. Double
      labelling techniques have greatly contributed to the discovery of the coexistence
      of two or more chemical compounds in the same cell. The in situ hybridization
      technique has recently become a productive addition to the tools available to the
      neuroscientist, especially when combined with immunocytochemistry to correlate
      mRNAs and protein expression. Even today, innovative roles for neurocytochemistry
      continue to be found. The newest approaches based on RT-PCR (reverse
      transcriptase-polymerase chain reaction) promise levels of sensitivity never
      reached before in in situ studies, and can provide simultaneous
      expression/functional data at the single-cell level.

PMID- 10076771
TI  - The tumours of the endocrine pancreas.
AB  - Tumours of the endocrine pancreas are rare entities with evidence of endocrine
      cell differentiation. Immunohistochemistry is the most reliable method used to
      study such tumours either for the identification of their hormonal product(s) or
      to explore functional aspects like proliferative activity or oncoprotein
      overexpression (e.g. p53). Most of the endocrine tumours of the pancreas are well
      differentiated and behave as benign or low grade malignant tumours. Poorly
      differentiated (small cell) endocrine carcinomas are rare and have a poor
      prognosis.

PMID- 10076772
TI  - Ki-ras and p53 gene mutations in pancreatic ductal carcinoma: a relationship with
      tumor phenotype and survival.
AB  - We investigated a series of clinically well documented pancreatic ductal
      adenocarcinomas for the presence of molecular alterations of the p53 and Ki-ras
      genes and their correlations with p53 nuclear immunohistochemical expression. The
      results were evaluated in comparison with cellular expression, by ductal cancer
      cells, of gastric (PGII) and intestinal (CAR-5) antigens and with several
      clinicopathologic parameters such as grade, stage, size and lymph-node status. Ki
      ras gene mutation at codon 12 was detected in 77.7% of cases with no relationship
      with tumor grade, stage, and survival of the patients. p53 gene mutations were
      found in 18/31 (58%) cases and p53 immunohistochemical overexpression was
      detected in 51/104 (49%) of cases. Both Ki-ras and p53 gene mutations were found
      in 13/31 (41.9%) of adenocarcinomas examined, while Ki-ras and p53 overexpression
      was detected in 19/45 (42.2%). A positive correlation between p53 overexpression
      and tumour grade was found (p0.0001) but no relationship was found between p53
      overexpression, tumor stage, lymph-node status and size of the tumors. A trend
      toward an association of p53 overexpression with poorer survival was found in
      patients with pancreatic cancers of the same grade, stage or with the same
      immunophenotype, but the data did not reach statistical significance. The
      expression of gastric and intestinal antigenic markers in pancreatic
      adenocarcinomas and the presence of molecular abnormalities analogous to those
      found in gastric and colorectal cancers suggest common genetic pathways in
      gastrointestinal and pancreatic carcinogenesis.

PMID- 10076773
TI  - The effects of epinephrine administration on impedance cardiographic measures of
      cardiovascular function.
AB  - The effects of epinephrine administration on cardiovascular function were
      examined in 26 men who were given a bolus injection of either 1:10,000
      epinephrine hydrochloride or physiological saline. Impedance cardiographic and
      continuous blood pressure measures were recorded during a 2-min pre-injection
      baseline and in the post-injection period. Compared to a saline control,
      epinephrine elicited greater shortening of heart period, pre-ejection period, and
      the R-B interval; greater increases in cardiac output, stroke volume, dZ/dt
      amplitude, Heather Index, and systolic and diastolic pressures; and greater
      decreases in total peripheral resistance (all P < 0.05). Left ventricular
      ejection time and the Q-R interval were not affected. The results indicate that
      inotropic indices that are readily measured by impedance cardiography should be
      considered as important non-invasive indices of adrenergically mediated responses
      to stress.

PMID- 10076774
TI  - Selection of actions in the basal ganglia-thalamocortical circuits: review and
      model.
AB  - The paper reviews the 20-year experience of recording impulse activity of neurons
      in the basal ganglia-thalamocortical circuits. These recordings were made from
      patients with Parkinson's disease who failed to respond to conventional medical
      treatment and who had undergone stereotaxic neurosurgery. When taken together,
      the results show that: (1) the basal ganglia-thalamocortical circuits become
      active only when a stimulus is attended or when a movement is voluntarily
      implemented, i.e. they are involved in the process of selection of an appropriate
      sensory stimulus for advanced processing and in the process of selection of an
      appropriate motor action for achieving a certain goal; (2) neuronal circuits
      responsible for assessment actions and for motor acts are segregated; (3)
      inhibitory opponent neuronal mechanisms are implemented for initiating and
      suppressing inappropriate actions; and (4) preparation to make different
      assessment actions (attentional set) is associated with different preparatory
      activities. To explain these findings a hypothesis of action programming has been
      formulated. According to it, the whole of human behavior is divided into separate
      sensory-motor-cognitive actions, while the brain in turn is divided into separate
      systems playing different roles in the organization of actions. The system for
      action selection that includes the basal ganglia-thalamic circuits plays a
      critical role in initiation of, preparation for, and suppression of these
      actions. The neuronal mechanisms for the system for action selection including
      mapping of actions, 'winner takes all' operations in the striatum, disinhibition
      and inhibition process in the thalamus are suggested and discussed.

PMID- 10076775
TI  - The sensitivity of instantaneous coherence for considering elementary comparison
      processing. Part I: The relationship between mental activities and instantaneous
      EEG coherence.
AB  - In this study the sensitivity of instantaneous EEG coherence for the description
      of the processual evolution of thinking processes is investigated. The adaptive
      estimation approach presented allows the calculation of the coherence function
      with high time and frequency resolution. On this basis the detection of time
      intervals with high synchronization phenomena is possible. The strength of
      coupling between different EEG channels may therefore be measured even for very
      short mental activities. The inclusion of the time component enables the
      calculation of very sensitive coherence parameters, such as the maximal coherence
      value or the length of time intervals with high synchronization during
      information processing. Based on these dynamic examinations, conceptual and
      imaginal representations are distinguishable for elementary cognitive processes.

PMID- 10076776
TI  - The sensitivity of instantaneous coherence for considering elementary comparison
      processing. Part II: Similarities and differences between EEG and MEG coherences.
AB  - The EEG (electroencephalogram) coherence depends on EEG deviation type. A high
      level of sensitivity of instantaneous coherence for investigating elementary
      cognitive tasks could be shown in the case of unipolar reference (ear lobe
      reference). In order to validate of this result the same investigations were
      performed for MEG (magnetoencephalogram) coherence, where EEG and MEG were
      measured simultaneously. A strong correlation between time intervals with high
      EEG and MEG coherence could be shown. The equivalence of the sensitivity of EEG
      and MEG coherence for the description of the dynamic behaviour of information
      processing and the distinction between different elementary cognitive tasks is
      proven statistically.

PMID- 10076777
TI  - What does the brain do while playing scrabble?: ERPs associated with a short-long
      term memory task.
AB  - Event-related brain potentials (ERPs) were recorded while subjects performed the
      scrabble paradigm, a cued recall task that demands retrieving semantic memory
      information from long-term memory since subjects are not exposed to a previous
      study phase. The task combines short- and long-term memory processes and consists
      of forming words from a set of letters presented in random order. Short-term
      memory was manipulated by varying the number of letters (three, four and five)
      presented to the subject, while semantic memory was examined by comparing correct
      trials with no response trials. Behavioral results reveal that the subjects
      performed the task serially, as denoted by a linear reaction time increment as
      the number of random letters in the set increased. Short-term memory procedures
      were reflected by an amplitude increase of the N200 and by an amplitude decrease
      of the P300 increasing the number of letters. Successfully retrieving semantic
      information from long-term memory was indexed by a negative slow wave recorded at
      left frontal and left central sites, and by a positive slow wave predominant over
      right hemisphere sites. These findings provide evidence that semantic retrieval
      memory involves activity from both left and right hemispheres.

PMID- 10076778
TI  - Risk and genetic factors in pancreatic cancer.

PMID- 10076779
TI  - Antimicrobial agents and Crohn's disease: do they have a therapeutic role?

PMID- 10076780
TI  - Usefulness of brushing urease test for diagnosis of Helicobacter pylori
      infection.
AB  - BACKGROUND AND AIMS: Gastric brushing cytology is an accurate technique for
      rapidly detecting Helicobacter pylori infection, but it is not routinely employed
      since the presence of personnel experienced in this field, is necessary in the
      endoscopy suite. To evaluate the diagnostic usefulness of rapid urease test
      carried out on cytological brushing. PATIENTS: A total of 143 consecutive
      patients with suspected Helicobacter pylori infection, referred for elective
      gastroscopy. METHODS: For each patient, 2 brushings were carried out and 4
      biopsies were taken from antral mucosa during gastroscopy. The former brushing
      was smeared on a slide, and stained by a rapid staining set for blood smears. The
      latter was used for rapid urease test, by shaking the brush into the urea broth.
      Two biopsies were used for rapid urease test and two for histologic examination.
      Histology was considered as the gold standard. RESULTS: Of 143 patients, 73 were
      diagnosed as Helicobacter pylori infected using histology. Six brushing slides
      were inadequate due to insufficient cytology material. Biopsy-rapid urease test
      and brushing-rapid urease test had similar sensitivity (87.3% vs 83.5%),
      specificity (98.4% vs 96.8%) and overall accuracy (92.3% vs 89.5%). In 62
      Helicobacter pylori infected patients, both rapid urease test techniques were
      positive. Brushing-rapid urease test became positive in a significantly shorter
      time than biopsy-rapid urease test (22 +/- 54 minutes vs 39 +/- 63 minutes; p <
      0.01). CONCLUSIONS: Brushing-rapid urease test is as accurate as biopsy-rapid
      urease test in detecting Helicobacter pylori infection, but it is significantly
      faster. Special care should be taken to carry out brushing adequately, to
      minimize the occurrence of false negatives.

PMID- 10076781
TI  - Use of antibiotics in the treatment of active Crohn's disease: experience with
      metronidazole and ciprofloxacin.
AB  - BACKGROUND AND AIMS: The use of antibiotics in the treatment of active Crohn's
      disease has recently increased on the assumption that enteral flora may play a
      role in the origin of symptoms and/or complications of Crohn's disease. The aim
      of this study was to evaluate retrospectively the efficacy of metronidazole
      and/or ciprofloxacin in the treatment of acute phases of Crohn's disease.
      METHODS: The clinical records of 233 inpatients seen at our clinic for active
      Crohn's disease and treated with metronidazole and/or ciprofloxacin (1 g daily
      each) during the period 1984-1996 were reviewed; the patients were divided into
      three groups according to antibiotic therapy. The primary criterion of success
      was the achievement of a complete or partial remission evaluated on the basis of
      the Simple Index; a secondary criterion of success was the efficacy of therapy on
      individual symptoms and signs. RESULTS: Similar rates of success were obtained
      with the three schemes of treatment: 70.6% with antibiotic combination, 72.8%
      with metronidazole, 69.0% with ciprofloxacin. The most frequent symptoms and
      signs such as diarrhoea, abdominal pain, fever, abdominal mass and abscesses
      improved in about 60% of patients in the three groups. Remission time after
      antibiotic treatment was about one year. Side effects requiring discontinuation
      of therapy occurred in about 20% of patients. CONCLUSIONS: Metronidazole and
      ciprofloxacin seem to be useful in treating active phases of Crohn's disease.
      These results strongly support the important role of faecal flora in causing
      Crohn's disease symptoms.

PMID- 10076782
TI  - The causation of Crohn's disease and treatment with antimicrobial drugs.

PMID- 10076783
TI  - Amantadine hydrochloride decreases serum ALT activity without effects on serum
      HCV-RNA in chronic hepatitis C patients.
AB  - BACKGROUND AND AIMS: To investigate the effects and tolerance of amantadine in
      chronic hepatitis C patients. PATIENTS AND METHODS: Forty consecutive patients,
      with biopsy proven chronic active hepatitis, were treated with amantadine 200 mg
      daily in the morning for two months. Nineteen patients were previous non
      responders to alpha-interferon, nine patients experienced hepatitis relapse after
      interferon treatment, and twelve patients had never been treated with antiviral
      drugs. Complete blood count, liver and renal function tests were performed two
      months before, at baseline, end of therapy and two months after its completion.
      RESULTS: None of the patients experienced significant side effects. Twenty-four
      patients (60%) showed a reduction of serum aminotransferase levels (twelve
      patients > 30% and twelve patients < 30% of their basal levels). The analysis of
      variance showed a significant reduction in aminotransferase levels at the end of
      treatment (F = 11, p < 0.0001). In four patients, aminotransferases returned to
      normal, but none of them cleared HCV-RNA. After the end of treatment, serum ALT
      returned to baseline values in all patients. CONCLUSIONS: Amantadine is well
      tolerated in chronic hepatitis C patients. The time-relation between therapy and
      reduction of serum aminotransferase levels in 60% of patients suggests a
      potential anti-inflammatory activity of the drug without an effect on viraemia.

PMID- 10076784
TI  - Amantadine in the treatment of patients with chronic hepatitis C.

PMID- 10076785
TI  - Influence of advanced age and related comorbidity on the course and outcome of
      acute pancreatitis.
AB  - BACKGROUND AND AIMS: Aging process and comorbidity have been held to influence
      the course and outcome of acute pancreatitis in elderly patients. The aim of the
      present study was to investigate this issue in a large series of patients > or =
      70 years of age suffering from acute pancreatitis. PATIENTS AND METHODS: A
      retrospectively study was carried out on 439 patients with a first episode of AP.
      The patients were divided into two age groups: < or = 69 years (n = 340) and > or
      = 70 years (n = 99). Differences in general characteristics, aetiological
      factors, blood tests and laboratory data, severity of the disease and outcome
      were evaluated. The presence of intercurrent diseases was also investigated in
      the two age groups. RESULTS: No significant difference was observed in the
      distribution of the various aetiological factors in the two age groups
      considered. The percentage of patients with necrotizing forms of AP, Ranson
      prognostic score for severity, local and systemic complications, the number of
      patients requiring surgical intervention or endoscopic sphincterotomy, as well as
      length of hospital stay were similar in the two groups. Considering the patients
      suffering from necrotizing acute pancreatitis, a significant increase (p = 0.01)
      in mortality was observed in > or = 70-year-old patients (25.8 vs 7.8%).
      Associated diseases were significantly more frequent in advanced age (63.6 vs
      41.4%; p = 0.0004), but comorbidity did not correlate with the presence of
      pancreatic necrosis, the need for surgery or endoscopic sphincterotomy, and with
      mortality. CONCLUSIONS: The results of this study suggest that advanced age and
      related comorbidity have only a limited influence on the course and outcome of
      acute pancreatitis.

PMID- 10076786
TI  - Assessment of mortality risk in acute pancreatitis: implications and importance.

PMID- 10076787
TI  - Extracorporeal lithotripsy of intrahepatic stones with associated strictures of
      intrahepatic biliary ducts.
AB  - BACKGROUND AND AIMS: Intrahepatic stones are a frequent disease in the Eastern
      world but rare in Western countries. Treatment is complex and often requires
      surgical intervention. Extracorporeal shock wave lithotripsy is a relatively
      recent technique, widely used in the treatment of stones in the gallbladder and
      common bile duct. It can also be used in the treatment of intrahepatic stones.
      The present study analyses the efficacy of extracorporeal shock wave lithotripsy
      in intrahepatic stones. PATIENTS AND METHODS: In our study, we used
      extracorporeal lithotripsy in six cases of intrahepatic stones (mean age 53
      years). In five of these cases deformities of the intrahepatic bile ducts were
      also present: stenoses and angulated strictures. The stones were in the right
      lobe of the liver in 5 patients, and in both lobes in 1 patient. Four patients
      had multiple stones and 2 a single stone, all varying in diameter from 6 to 25
      mm. The stones were localized radiologically with contrast medium through a
      drainage tube. The technique does not require anaesthesia. An average of three
      lithotripsy sessions were necessary, with a mean total of 8050 shock waves per
      patient. RESULTS: Successful fragmentation was obtained in 5 out of 6 patients,
      while the remaining subsequently underwent surgery. No complications were
      observed. CONCLUSIONS: Extracorporeal shock wave lithotripsy proved to be
      effective, easy to perform and safe for the treatment of intrahepatic stones.

PMID- 10076788
TI  - The treatment of intrahepatic stones: the case for extracorporeal shockwave
      lithotripsy.

PMID- 10076789
TI  - Wilson's disease with concomitant beta thalassaemia and factor V deficiency.
AB  - A case of late presentation of Wilson's disease in a female with a thalassaemic
      trait is reported in whom diagnosis of Factor V deficiency was made. Despite
      ignoring the disease for years the patient had compensated cirrhosis. She had a
      dramatic family history of Wilson's disease affecting at least two brothers and
      two sisters. Moreover, her haematologic problems were not clinically revealed
      until diagnosis had been made on the basis of suspicions arising from laboratory
      results. The therapy of choice for hepatolenticular degeneration was not feasible
      due to the patient's refusal. Zinc salts were, therefore, administered. To our
      knowledge the association of such rare genetic disorders has not been reported.

PMID- 10076790
TI  - Cushing's syndrome due to ectopic adrenocorticotropic hormone production by a non
      metastatic gastrinoma after long-term conservative treatment of Zollinger-Ellison
      syndrome.
AB  - This report concerns a case of a Cushing's syndrome 10 years after first
      diagnosis of a Zollinger-Ellison syndrome within the same patient. In a 69-year
      old female patient symptoms of hypergastrinaemia have been successfully treated
      with a proton pump inhibitor. Cushing's syndrome was the result of ectopic
      adrenocorticotropic hormone production by a large cystic gastrin-producing tumour
      of the pancreatic tail. After resection by subtotal pancreatectomy serum
      adrenocorticotropic hormone, cortisol, gastrin levels and secretin infusion test
      returned to normal. In contrast to all other previously published cases of
      ectopic adrenocorticotropic hormone syndrome associated with Zollinger-Ellison
      syndrome, this tumour had not metastasized into the liver and did not show local
      invasive growth.

PMID- 10076791
TI  - Adenocarcinoma of the colon and rectum: some reflections on the immediate and
      long-term results of surgery.
AB  - Colorectal cancer continues to be a major public health problem in western
      countries. Although some studies have reported an improvement in disease-free and
      overall survival, few of the diagnostic and therapeutic procedures proposed have
      found unanimous consent. We report some reflections on both the immediate and the
      long-term results of colorectal cancer surgery on the basis of our experience,
      represented by 1164 patients with histologically proven colorectal carcinoma,
      admitted to the Institute of General Surgery of Parma University between 1976 and
      1993 and operated on by the same surgical team, in order to provide data for
      scientific discussion. A curative resection was possible in 67.9% of the cases.
      Our experience shows that many colorectal cancer patients will be cured with
      aggressive surgery, although, in recent years, adjuvant therapy for colorectal
      cancer has advanced considerably. Statistical analyses reveal that an
      unfavourable prognosis is correlated with variables indicative of advanced
      disease. Concerning the problem of local recurrences, our results demonstrate
      that surgery is the only therapeutic option providing tangible results, and that
      intense follow-up leads to a greater number of resections carried out for local
      recurrence and to improved 5-year survival. Comparison of studies and scientific
      discussions can prove useful, above all regarding secondary prevention and, in
      particular, the identification of patients at risk who should undergo screening
      for early diagnosis and early surgical treatment.

PMID- 10076792
TI  - Therapeutic news on Helicobacter pylori from Budapest and Wien.
AB  - Helicobacter pylori is the most common infection in the world and is associated
      with some of the most prevalent gastroduodenal diseases. There is now
      considerable evidence that Helicobacter pylori eradication not only heals
      duodenal ulcer, but also prevents ulcer recurrences and probably ulcer
      complication. It is, therefore, universally accepted that, all patients with
      duodenal ulcer disease should receive eradication therapy. This review represents
      an attempt to summarize and analyse all the regimens proposed in September at the
      last International Meetings in Budapest and Wien in which different anti
      Helicobacter pylori regimens have been used. Despite the large number of clinical
      trials which had been performed, no significant advances have been made in
      relation to Helicobacter pylori therapy, so the "optimal" eradication treatment
      still remains a matter of debate. More than 10,000 patients were treated and most
      of them (around 5000) were found to have peptic ulcer disease which represents no
      more than 10-15% of our endoscopic findings. The proton pump inhibitor regimens
      are definitely the most representative drug policy appearing in the literature
      and despite several attempts (proton pump inhibitor given for less, one, or more
      than one week) the short one-week regimen (The Maastricht regimen) has been
      recognized as the most promising treatment.

PMID- 10076793
TI  - Is adhesion molecule ICAM-1 expression correlated with Crohn's clinical
      subgroups?

PMID- 10076794
TI  - Melena: an unusual manifestation of Whipple's disease.

PMID- 10076795
TI  - An update on post-transfusion hepatitis in Italy.

PMID- 10076796
TI  - Affinity interactions.

PMID- 10076797
TI  - Poliovirus and its cellular receptor: a molecular genetic dissection of a
      virus/receptor affinity interaction.
AB  - The ability of a virus to attach to a susceptible host cell is of utmost
      importance for the initiation of viral life cycle. Cell surface proteins called
      viral receptors mediate the initial steps of virus attachment and uptake.
      Poliovirus (PV) is one of the most studied animal viruses and its interaction
      with its cellular receptor, the human poliovirus receptor (hPVR) has been well
      characterized. This review will present our current understanding of the PV/hPVR
      interaction at the genetic and biochemical level. In addition, we will also
      discuss the implications of the PV/hPVR interaction on PV tissue tropism and the
      evolution of the three PV serotypes.

PMID- 10076798
TI  - Thermodynamic characterization of affinity maturation: the D1.3 antibody and a
      higher-affinity mutant.
AB  - Understanding the structural and dynamic determinants of binding free energy in
      the antigen-antibody bond is of great interest. Much work has focused on
      selective mutations in order to locate key interaction residues, but this
      generally results in reduced affinity. The present work instead examines a higher
      affinity mutant to characterize the thermodynamic pathway of the affinity
      maturation process. We have compared the antigen binding energetics of scFv D1.3,
      an anti-hen egg lysozyme single chain antibody, with a higher-affinity mutant
      (Hawkins, R. E., Russell, S. J., Baier, M. and Winter, G. (1993). J. Mol. Biol.
      234, 958-964). The mutant has five-fold higher affinity for lysozyme but nearly
      the same enthalpy and heat capacity change upon binding, as measured by
      isothermal titration calorimetry. Thus, much of the binding free energy
      difference can be attributed to entropic effects. Fluorescence quenching with
      acrylamide indicates that this more favorable entropy change may result from a
      more flexible mutant-lysozyme complex and thus be a configurational entropy
      effect.

PMID- 10076799
TI  - Interactions of calmodulin with metal ions and with its target proteins revealed
      by conformation-sensitive monoclonal antibodies.
AB  - Two monoclonal antibodies (mAbs) raised against bovine calmodulin (CaM), CAM1 and
      CAM4, enable one to monitor conformational changes that occur in the molecule.
      The interaction of CAM1 with CaM depends on the Ca2+ occupancy of its Ca(2+)
      binding sites. CAM4, in contrast, interacts with CaM in a Ca(2+)-independent
      manner, interacting with both holoCaM and EGTA-treated CaM to a similar extent.
      Their interaction with various CaMs, CaM tryptic fragments and chemically
      modified CaM, as well as molecular graphics, led to identification of the CAM1
      and CAM4 epitopes on the C- and N-terminal lobes of CAM respectively. The two
      mAbs were used as macromolecular probes to detect conformational changes
      occurring in the CaM molecule upon binding of metal ions and target proteins and
      peptides. MAb CAM1 successfully detected changes associated with Al3+ binding
      even in the presence of Ca2+, indicating that Al3+ and Ca2+ ions may bind to the
      protein simultaneously, leading to a new conformation of the molecule. MAbs CAM1
      and CAM4 were used to follow the interactions of CaM with its target peptides and
      proteins. Complexes with melittin, mastoparan, calcineurin and phosphodiesterase
      showed different immunological properties on an immuno-enzyme electrode,
      indicating unique structural properties for each complex.

PMID- 10076800
TI  - A citrate-binding site in calmodulin.
AB  - Calmodulin (CaM) is a major Ca2+ messenger which, upon Ca2+ activation, binds and
      activates a number of target enzymes involved in crucial cellular processes. The
      dependence on Ca2+ ion concentration suggests that CaM activation may be
      modulated by low-affinity Ca2+ chelators. The effect on CaM structure and
      function of citrate ion, a Ca2+ chelator commonly found in the cytosol and the
      mitochondria, was therefore investigated. A series of structural and biochemical
      methods, including tryptic mapping, immunological recognition by specific
      monoclonal antibodies, CIDNP-NMR, binding to specific ligands and association
      with radiolabeled citrate, showed that citrate induces conformational
      modifications in CaM which affect the shape and activity of the protein. These
      changes were shown to be associated with the C-terminal lobe of the molecule and
      involve actual binding of citrate to CaM. Analyzing X-ray structures of several
      citrate-binding proteins by computerized molecular graphics enabled us to
      identify a putative citrate-binding site (CBS) on the CaM molecule around
      residues Arg106-His107. Owing to the tight proximity of this site to the third
      Ca(2+)-binding loop of CaM, binding of citrate is presumably translated into
      changes in Ca2+ binding to site III (and indirectly to site IV). These changes
      apparently affect the structural and biochemical properties of the conformation
      sensitive protein.

PMID- 10076801
TI  - Reactivation of glyceraldehyde-3-phosphate dehydrogenase using conjugates of
      monoclonal antibodies with polyelectrolyte complexes. An attempt to make an
      artificial chaperone.
AB  - The simplified model of chaperone action when the inactive misfolded forms are
      removed from the reaction media preventing aggregation was developed using
      antibodies in combination with polyelectrolyte complexes. The antibodies, which
      bind specifically inactive dimers of glyceraldehyde-3-phosphate dehydrogenase but
      not native tetramers, were coupled covalently to poly(methacrylic acid). The
      treatment of inactivated GAPDH with this conjugate followed by its precipitation
      after equimolar addition of polycation, poly-(N-ethyl-4-vinylpyridinium bromide),
      resulted in a significant increase in the specific activity of the enzyme.

PMID- 10076802
TI  - Prediction of molecular recognition-enhanced phenobarbital extraction based on
      solvatochromic analysis.
AB  - The extraction efficiency for organic molecules using synthetic receptors is
      highly dependent on solvent properties. Solvent influences the partitioning of
      both the desired compound and the interfering species. Solvent also influences
      the solubility of the receptor and its affinity for the substrate. Therefore the
      free energy involved in extraction can be optimized by using a carefully selected
      solvent. In this paper we demonstrate the use of a solvatochromic model to
      predict the influence of solvent dipolarity, H-bond acidity and H-bond basicity
      on selectivity and yield of phenobarbital extraction. We also used this method to
      estimate the purity and yield of phenobarbital extraction in 12 poly(vinyl
      chloride) plasticizers and solvents. This approach can be generalized for
      assisting the selection of optimal solvent and provide insight into the rational
      design of solvent and receptor for industrial extractions.

PMID- 10076803
TI  - Histidine mapping of serine protease: a synergic study by IMAC and molecular
      modelling.
AB  - The immobilized metal ion affinity (IMA) interaction of different serine
      proteases, namely porcine and bovine trypsins and BPN' and Carlsberg subtilisins,
      was studied on Sepharose-IDA-CuII. Both trypsins were resolved into their
      different subspecies, whereas the subtilisins appeared as only one species. The
      use of diethyl pyrocarbonate-modified enzymes demonstrated the contribution of
      histidine(s) as the sole interacting site(s). The use of different peptidic and
      chemical inhibitors complexed to the enzymes confirmed the contribution of
      histidine(s) as the interacting site(s) and further resulted in different
      chromatographic patterns for the free and complexed serine proteases. Comparison
      of the chromatographic data for each enzyme with the accessible surface area
      calculation by molecular modelling on the available crystallographic structure
      allowed us to hypothesize a map of the surface-accessible histidine on each
      enzyme.

PMID- 10076804
TI  - Sjogren's autoimmunity: how perturbation of recognition in endomembrane traffic
      may provoke pathological recognition at the cell surface.
AB  - CD4 T cell antigen recognition requires presentation by major histocompatibility
      complex Class II molecules (MHC II). B cell surface immunoglobulins recognize
      antigens independently of MHC II, but activation typically requires CD4 cell
      cytokines as accessory signals. Plasma membrane-endomembrane traffic in lacrimal
      gland acinar cells, targets of autoimmune activity in Sjogren's syndrome, may
      satisfy both requirements. The Golgi protein galactosyltransferase and the
      lysosomal proteins cathepsin B and cathepsin D appear at the plasma membranes
      during sustained secretomotor stimulation. The RNA transcription termination
      factor La, a frequent target of Sjogren's autoantibodies, appears in the acinar
      cell cytoplasm and plasma membranes during viral infection and during in vitro
      exposure to cytokines. MHC II cycle through endomembrane compartments which
      contain La, galactosyltransferase, cathepsin B and cathepsin D and which are
      sites of proteolysis. This traffic may permit trilateral interactions in which B
      cells recognize autoantigens at the surface membranes, CD4 T cells recognize
      peptides presented by MHC II, B cells provide accessory signals to CD4 T cells,
      and CD4 T cells provide cytokines that activate B cells. Acinar cells stimulate
      lymphocyte proliferation in autologous mixed cell reactions, confirming that they
      are capable of provoking autoimmune responses.

PMID- 10076805
TI  - Recombinant soluble low-density lipoprotein receptor fragment inhibits common
      cold infection.
AB  - A fragment of the human low-density lipoprotein receptor encompassing the seven
      ligand-binding repeats fused to a C-terminal oligo-His tag was expressed in Sf9
      insect cells. The melittin signal sequence encoded in the baculovirus vector led
      to secretion of the protein into the cell supernatant in a soluble form. The
      receptor fragment bound its natural ligand beta-migrating very-low-density
      lipoprotein and human rhinovirus serotype 2 in non-reducing ligand blots.
      Infection of all minor group human rhinovirus serotypes investigated was
      inhibited by the presence of the receptor fragment during viral challenge of HeLa
      cells. Infection is inhibited by aggregation of the virions.

PMID- 10076806
TI  - Freeze-thaw immobilization of liposomes in chromatographic gel beads: evaluation
      by confocal microscopy and effects of freezing rate.
AB  - Biological membranes immobilized in chromatographic gel beads constitute a
      multifunctional affinity matrix. Membrane protein-solute interactions and drug
      partitioning into the lipid bilayers can conveniently be studied. By the use of
      confocal laser-scanning microscopy (CLSM) the distribution of immobilized model
      membranes in the beads has been visualized for the first time. Freeze-thaw
      immobilized liposomes in Superdex 200 gel beads were situated in a thick shell
      surrounding a liposome-free core. The amount of phospholipids immobilized by
      freeze-thawing was dependent on the temperature in the cooling bath and the type
      of test tube used. A bath temperature of -25 degrees C gave higher immobilization
      yield than freezing at -75 or -8 degrees C did. Freeze-thawing in the presence of
      liposomes did not affect the gel bead shape or the refractive index homogeneity
      of the agarose network of the beads, as shown by confocal microscopy.

PMID- 10076807
TI  - Biomembrane affinity chromatographic analysis of nitrobenzylthioinosine binding
      to the reconstituted human red cell nucleoside transporter.
AB  - Solute interactions with membrane proteins can be analyzed by biomembrane
      affinity chromatography (BAC), previously applied to the human red cell glucose
      transporter. As a novel example, frontal BAC analysis of interactions between the
      nucleoside transport inhibitor nitrobenzylthioinosine (NBTI) and immobilized
      reconstituted nucleoside and glucose transporters from human red cells revealed
      two binding sites, presumably corresponding to the two transporters. The
      affinities and amounts of sites were determined by use of a double rectangular
      hyperbolic equation. The Kd value for NBTI binding to the nucleoside transporter
      in egg phospholipid proteoliposomes was 0.38 +/- 0.08 nM (22 degrees C, I = 0.16,
      pH 7.4), lower than previously reported for reconstituted systems. The molar
      ratio between the amounts of nucleoside transporter sites for NBTI and glucose
      transporter sites for cytochalasin B was 4.5 +/- 0.6%.

PMID- 10076808
TI  - Some new developments and challenges in non-covalent molecular imprinting
      technology.
AB  - The technique of molecular imprinting allows the formation of specific
      recognition and catalytic sites in macromolecules via the use of templates.
      Molecularly imprinted polymers have been applied in an increasing number of
      applications where molecular binding events are of interest. These include the
      use of molecularly imprinted polymers as tailor-made separation materials,
      antibody and receptor binding site mimics in recognition and assay systems,
      enzyme mimics for catalytic applications and as recognition elements in
      biosensors. The stability and low cost of molecularly imprinted polymers make
      them advantageous for use in analysis as well as in industrial-scale production
      and application.

PMID- 10076809
TI  - Insights into the origins of binding and the recognition properties of
      molecularly imprinted polymers prepared using an amide as the hydrogen-bonding
      functional group.
AB  - Molecularly imprinted polymers (MIPs) prepared using an amide hydrogen-bonding
      functional monomer (acrylamide) exhibited efficient enantiomeric recognition
      properties in both organic and aqueous media in the HPLC mode. The results
      indicate that the amide functional groups formed strong hydrogen-bonding
      interactions with the template molecule, and specific recognition sites were
      created within the polymer matrix during the imprinting process. When Boc-L-Trp
      was used as the template, an MIP prepared in a polar organic solvent
      (acetonitrile) using acrylamide as the functional monomer showed better
      enantiomeric recognition of Boc-Trp than the MIPs prepared in the same solvent
      using an acidic (methacrylic acid) or a basic (2-vinylpyridine) functional
      monomer or a combination of an acidic and a basic functional monomer (methacrylic
      acid + 2-vinylpyridine). Our results indicate that in organic media the degree of
      retention of the sample molecule on the imprinted polymer was controlled by
      hydrogen-bonding interactions between the sample molecule and the polymer, while
      in aqueous media it was determined to a considerable extent by hydrophobic
      interactions. In both media the shape, size and the nature of the hydrogen
      bonding groups of the sample molecules were all important factors in determining
      the enantiomeric and substrate selectivity. In the aqueous media, however, the
      hydrophobicity of the sample molecules was also found to play an important role.

PMID- 10076810
TI  - A new application of molecularly imprinted materials.
AB  - We have studied the possibility of shifting a thermodynamically unfavourable
      enzymatic equilibrium towards product formation via the addition of a highly
      specific adsorbent. The commercially interesting enzymatic condensation of Z-L
      aspartic acid with L-phenylalanine methyl ester to the sweetener aspartame was
      chosen as the model system. Extremely stable and specific adsorbents for the
      product Z-L-Asp-L-Phe-OMe (Z-aspartame) were prepared using the emerging
      technique of molecular imprinting. A considerable increase (40%) in the yield of
      product was obtained when such adsorbents were present during the enzymatic
      reaction. The message of this investigation is that the use of such specific,
      sterilizable adsorbents should be considered for enzymatic processes to increase
      the yield. Finally, the direct isolation of a product formed by the retrieval of
      the adsorbents carrying the product can be envisaged, especially if the
      adsorbents are magnetic.

PMID- 10076811
TI  - Towards the rational design of molecularly imprinted polymers.
AB  - Efforts to elucidate the mechanisms underlying the formation of binding sites in
      molecularly imprinted polymers (MIPs) and of MIP-ligand binding events are
      presented in the context of a thermodynamic treatment of MIP recognition
      phenomena.

PMID- 10076812
TI  - Spectroscopic studies of the molecular imprinting self-assembly process.
AB  - A method for the rapid estimation of the extent of complex formation in molecular
      imprinting prepolymerization mixtures is described. By the use of a UV
      spectroscopy titration procedure, apparent binding constants for such self
      assembly processes have been obtained. This method was used for comparison of the
      interactions between a dipeptide template (N-acetyl-L-phenylalaninyl-L
      tryptophanyl methyl ester) and the functional monomer methacrylic acid, and the
      monomer analogues acetic acid and trifluoroacetic acid. The importance of
      template-monomer association during the molecular imprinting prepolymerization
      phase is discussed with respect to the systems studied.

PMID- 10076813
TI  - Novel chiral recognition elements for molecularly imprinted polymer preparation.
AB  - The use of a novel chiral functional monomer system in molecular imprinting
      protocols is described. The monomer, dibenzyl (2R,3R)-O-monoacryloyl tartrate,
      possesses a hydroxyl moiety which can be used to direct template-functional
      monomer interactions during molecular imprinting polymerization. This system
      simultaneously positions benzyl ester-protected carboxyl groups in close
      proximity to the template, which upon deprotection yield recognition sites with
      stronger ligand-binding capacities. Furthermore, the inherent chirality of the
      monomer engenders the polymer with an inbuilt preference for a given
      stereoisomer. Application of the system to the molecular imprinting of the
      cinchonidine alkaloids (+)-cinchonine and (-)-cinchonidine yielded
      stereoselective polymers. The effect of imprinting (+)-cinchonine produced a
      polymer which more than reversed the inherent chiral selectivity of the chiral
      monomer residues present in the matrix.

PMID- 10076814
TI  - Phage viability in organic media: insights into phage stability.
AB  - The stability of the filamentous phages derived from phagemid pG8H6 has been
      examined in a range of solvents and solvent mixtures. The results show an
      enhanced capacity to infect E. coli after exposure to various organic solvent
      water mixtures. The dependence of stability upon solvent hydrophobicity was
      demonstrated. Furthermore, conditions have been identified which should allow the
      application of phage display libraries based upon pG8H6 in organic media.

PMID- 10076815
TI  - The rational use of hydrophobic effect-based recognition in molecularly imprinted
      polymers.
AB  - A novel molecularly imprinted polymer (MIP) system selective for D-phenylalanine
      is described where polymerization is performed in aqueous solution. The unique
      polymer system comprises a hydrophobic moiety-selective functional monomer,
      polymerizable beta-cyclodextrin, an electrostatic interacting functional monomer,
      2-acryloylamido-2-methylpropane sulfonic acid (AMPSA), and the crosslinking agent
      N,N'-diacryloylpiperazine. Chromatographic evaluation of polymer-ligand
      recognition characteristics demonstrated ligand selectivity by the MIP and that
      optimal recognition was achieved through a balance of hydrophobic and
      electrostatic ligand-polymer interactions, indicating that recognition in these
      systems is regulated by enthalpy-entropy compensation. The imprinting effect was
      shown to be sufficient to reverse the inherent selectivity of cyclodextrin for L
      phenylalanine.

PMID- 10076816
TI  - Theophylline molecularly imprinted polymer dissociation kinetics: a novel
      sustained release drug dosage mechanism.
AB  - The template release kinetics of theophylline molecularly imprinted polymers has
      been examined with a view to determining their potential as a controlled release
      drug dosage form. The basis for the ligand selectivity of these polymers has been
      shown through the demonstration of pre-polymerization template-monomer
      complexation and HPLC studies of the product polymer ligand selectivities. The
      release kinetics shows a dependence upon template loading and pH. Small
      differences in release characteristics between imprinted and non-imprinted
      (reference) polymers have been observed.

PMID- 10076817
TI  - Crown ethers as a tool for the preparation of molecularly imprinted polymers.
AB  - Molecularly imprinted polymers have been prepared against aniline and a bis
      aniline compound, making use of a crown ether (18-crown-6) to solubilize the
      monomer-template complexes. Subsequent chromatographic rebinding studies in the
      absence of crown ether revealed regioselectivity for the templates in the
      respective polymers. This study indicates that crown ethers can be potentially
      useful in conjunction with molecular imprinting to solubilize and imprint organic
      solvent-insoluble compounds.

PMID- 10076818
TI  - IRIS 97: an innovative protein A-peptidomimetic solid phase medium for antibody
      purification.

PMID- 10076819
TI  - Use of weak monoclonal antibodies for affinity chromatography.
AB  - When using weakly interacting ligands in affinity chromatography, it is possible
      to take advantage of a true chromatographic process in the separation, as
      compared with traditional affinity chromatography which is rather an on/off
      process. In this work, weak monoclonal antibodies were immobilized on a silica
      and a perfusion-type support (POROS AL) and used for high-performance liquid
      affinity chromatography (HPLAC). Similar carbohydrate antigens were separated
      under isocratic conditions according to their weak interaction with the
      immobilized monoclonal antibody. The affinity of the antibodies was adjusted with
      temperature and pH to modify the separation. The productivity of the
      chromatographic system was increased with the immobilized perfusion support but
      at the expense of loss of plate numbers. This study clearly demonstrates the
      potential of weak affinity biological interactions as a basis for chromatographic
      separation.

PMID- 10076820
TI  - Screening for weak monoclonal antibodies in hybridoma technology.
AB  - As the interest in weak-affinity antibodies has been widened by their
      introduction to various analytical techniques such as HPLC, capillary
      electrophoresis and biosensors, there has been a need for new
      screening/monitoring methods. In this study, weak-affinity chromatography was
      adopted to screen/monitor directly for monoclonal antibodies in ascites.
      Monoclonal antibodies against a carbohydrate antigen (maltohexaose) were used to
      evaluate this approach. In short, malthohexaose was immobilized on an HPLC
      support in such a configuration to allow, during HPLC, retardation of weak
      monoclonal antibodies. Based on the retention, the affinity or the avidity, as
      determined by the presence of multiple binding of the monoclonal antibody towards
      antigen, can be estimated. In this way it is possible to select clones of
      hybridomas that produce desired weak monoclonal antibodies. Adjustments in
      temperature (10-20 degrees C) were used to moderate the retention and hence
      affinity of the weak monoclonal antibodies during chromatography.

PMID- 10076821
TI  - Affinity of recombinant antibody and antibody fragment binding to human
      thyroglobulin: potential applications in gene therapy.
AB  - Recombinant antibodies and antibody fragments are currently being produced. They
      can be used in vitro for the structural study of antigen-antibody interactions
      for instance, but their in vivo production may have applications for gene therapy
      of certain cancers and severe viral diseases and in developing new animal models
      of autoimmune disease. We report here these two types of applications using a
      recombinant antihuman thyroglobulin (hTg) antibody.

PMID- 10076822
TI  - Structure of the IgG-binding ligand of the T-gel.
AB  - We examine the ligand requirements for the divinylsulphone (DVS) based T-gel to
      bind immunoglobulins. The original gel consisted of 2-mercaptoethanol coupled to
      a DVS activated support, with both the thioether and sulphone sulphurs thought
      necessary for protein binding. No differences in the capacity for human IgG were
      observed for a highly activated gel coupled with mercaptoethanol, or when the
      same activated gel was incubated at high pH to hydrolyse the majority of its
      reactive groups before the remainder were coupled with the thiol, indicating that
      the thioether S may be replaced with a hydroxyl O. Increasing the time of the DVS
      activation results in gels with higher concentrations of immobilised sulphone but
      lower concentrations of active groups. The IgG capacities of the mercaptoethanol
      coupled gels were found to increase with the time of the activation reaction,
      which may be exploited to produce high capacity gels while minimising the
      concentration of DVS. Reducing the vinyl of the DVS-activated gel with
      borohydride was found to decrease the amount of protein binding, with residual
      binding being attributed to the presence of hydrolysed or cross-linked sulphones
      in the gel. Reacting the activated gels with amines decreased the capacity for
      IgG still further, suggesting that not only are these ligands unable to bind IgG,
      they also prevent its interacting with neighbouring sulphones, perhaps due to the
      small amount of positive charge they carry.

PMID- 10076823
TI  - Identification of peptides that bind to the constant region of a humanized IgG1
      monoclonal antibody using phage display.
AB  - The pFc' fragments of a humanized IgG1 monoclonal antibody were generated by
      digestion with immobilized pepsin. These pFc' fragments were separated from
      F(ab')2 fragments by affinity chromatography. The pFc' fragments corresponding to
      the constant region of the humanized IgG1 monoclonal antibody were used as
      targets for phage display using variable-length peptide libraries. Interacting
      phage-displayed peptides were selected by repetitious cycles of target screening
      and phage amplification. Peptide sequences, deduced by sequencing DNA from
      isolated phage, were aligned and analyzed for amino acid motifs against each
      other and protein A. These results indicated that an amino acid motif has been
      identified using phage display technology that is sufficient for pFc' binding.
      Furthermore, the peptides derived from this study may prove useful in the
      development of peptidomimetic alternatives to protein A for use in affinity
      chromatography.

PMID- 10076824
TI  - Making antibody and peptide ligands by repertoire selection technologies.

PMID- 10076825
TI  - Immunoglobulin specificity of TG19318: a novel synthetic ligand for antibody
      affinity purification.
AB  - A synthetic ligand [TG19318], able to mimic protein A in the recognition of the
      immunoglobulin Fc portion, has been previously identified in our laboratory
      through the synthesis and screening of multimeric combinatorial peptide
      libraries. In this study we have fully characterized its applicability in
      affinity chromatography for the downstream processing of antibodies, examining
      the specificity and selectivity for polyclonal and monoclonal immunoglobulins
      derived from different sources. Ligand specificity was broader than protein A,
      since IgG deriving from human, cow, horse, pig, mouse, rat, rabbit, goat and
      sheep sera, IgY obtained from egg yolk, and IgM, IgA and IgE were efficiently
      purified on TG19318 affinity columns. Adsorbed antibodies were conveniently
      eluted by a buffer change to 0.1 M acetic acid or 0.1 M sodium bicarbonate pH 9,
      with full retention of immunological properties. Monoclonal antibodies deriving
      from cell culture supernatants or ascitic fluids were also conveniently purified
      on TG19318 affinity columns, even from very diluted samples. The affinity
      constant for the TG19318-IgG interaction was 0.3 microM, as determined by optical
      biosensor measurements. Under optimized conditions, antibody purity after
      affinity purification was close to 95%, as determined by densitometric scanning
      of SDS-PAGE gels of purified fractions, and maximal column capacity reached 25 mg
      Ig/ml support. In vivo toxicity studies in mice indicated a ligand oral toxicity
      greater than 2000 mg kg-1 while intravenous toxicity was close to 150 mg kg-1.
      Validation of antibody affinity purification processes for therapeutic use, a
      very complex, laborious and costly procedure, is going to be simplified by the
      use of TG19318, which could reduce considerably the presence of biological
      contaminants in the purified preparation, a very recurrent problem when using
      recombinant or extractive biomolecules as affinity ligands.

PMID- 10076826
TI  - Capillary affinophoresis as a versatile tool for the study of biomolecular
      interactions: a mini-review.
AB  - Combination of capillary electrophoresis and bioaffinity interaction gave rise to
      powerful research tools for analyzing molecular recognition. They take advantages
      of the electrophoretic behavior of the complex formed between a target
      biomolecule and a specially designed mobile ligand molecule (affinophore or
      affinity probe), and enable detection of complex formation, determination of the
      equilibrium constants and stoichiometry, etc.

PMID- 10076827
TI  - Capillary electrophoresis for the study of affinity interactions.
AB  - Molecular recognition may be characterized both qualitatively and quantitatively
      by electrophoretic methods if complexed molecules differ in electrophoretic
      mobility from unbound ones. The use of capillary zone electrophoresis (CE) for
      the characterization of affinity interactions is advantageous because of the high
      resolution, reproducibility and wide applicability of the technique and because
      of the mild conditions, i.e., physiological buffers without additions of organics
      or detergents, that are often sufficient for highly efficient separations. CE
      gives the ability to characterize binding between small amounts of unlabelled
      reactants in solution, has few requirements for special characteristics of the
      interacting molecules and is also applicable to the study of interactions of
      individual components in mixtures, as detection of binding and analytical
      separation are achieved in one step. This is unique compared with other
      techniques for the study of non-covalent interactions. The advantages and
      disadvantages of using CE to demonstrate molecular interactions, to screen for
      specific ligand binding in complex mixtures and to calculate binding constants
      will be discussed.

PMID- 10076828
TI  - Application of multichannel flow electrophoresis to separation of biomolecules: a
      survey.
AB  - Multichannel flow electrophoresis (MFE) is a newly developed method for
      continuous separation of biological products at a preparative scale, In this
      short survey, the application of MFE in the separation of proteins, enzymes and
      antibodies are overviewed.

PMID- 10076829
TI  - Electrophoretic affinity chromatography: method validation.
AB  - A new method for preparative-scale separation of biomolecules, electrophoretic
      affinity chromatography (EAC), is proposed in this paper. Separation by EAC is
      carried out in a long and ribbon-like multicompartment electrolyser separated by
      membranes, in which the two central compartments are used for packing the gel
      matrix and for sample loading respectively. Next to the central compartments are
      the elution compartments and electrode compartments. The electric field is
      applied perpendicular to the fluid flow in the compartments. Adsorption and
      desorption steps may both be carried out in the presence of an electric field,
      which transports the target components into the gel compartment for adsorption
      and the impurities into the elution compartments for washing. After the
      adsorption step an elution solution is introduced and the product is released
      from the gel matrix and washed out. Separation of human serum albumin (HSA) from
      human serum gives HSA product of high purity, as demonstrated by isoelectric
      focusing analysis. The characteristics of electrophoretic binding of HSA on Blue
      Sepharose Fast Flow are examined. The preliminary results show that this new
      method has advantages in terms of high rate of mass transfer and ease of scaling
      up, which are of particular interest when large-scale separation of biomolecules
      is considered.

PMID- 10076830
TI  - Hyphenated thermal field flow fractionation--capillary electrophoresis.
AB  - The possibility was considered to use the transverse thermophoresis of analytes
      in the capillary for capillary electrophoresis (CE) to control the separation
      process, decrease the peak width due to thermal effects and provide new
      separation parameters in CE. As the examination has shown, in non-aqueous buffers
      the Joule heating in the capillary for CE can provide transverse temperature
      gradients comparable with the temperature gradients in conventional devices for
      thermal field flow Fractionation (ThFFF). It was proposed to use the non-uniform
      velocity profile of analytes caused by the transverse temperature gradient and
      the temperature dependence of the buffer viscosity for the FFF-like separation of
      analytes besides CE separation. The expressions for the peak parameters have been
      derived, where the non-uniform transverse analyte concentration distribution due
      to the thermophoresis is taken into account, and the possibilities based on FFF
      CE principles are discussed. As possible objects of this hyphenated technique,
      macromolecules and particles are considered.

PMID- 10076831
TI  - Measurement of antigen-antibody interactions with biosensors.
AB  - The introduction in 1990 of a new biosensor technology based on surface plasmon
      resonance has revolutionized the measurement of antigen-antibody binding
      interactions. In this technique, one of the interacting partners is immobilized
      on a sensor chip and the binding of the other is followed by the increase in
      refractive index caused by the mass of bound species. The following
      immunochemical applications of this new technology will be described: (1)
      functional mapping of epitopes and paratopes by mutagenesis; (2) analysis of the
      thermodynamic parameters of the interaction; (3) measurement of the concentration
      of biologically active molecules; (4) selection of diagnostic probes.

PMID- 10076832
TI  - A holographic sensor based on a rationally designed synthetic polymer.
AB  - A new silver halide-containing holographic recording material has been designed
      and developed specifically for holographic chemical sensors. The hologram enables
      very small volume changes to be measured in a polymer layer throughout which the
      hologram is located. The holographic film is based on a fine-grain silver bromide
      emulsion suspended in a poly(vinyl alcohol) matrix crosslinked with Cr(III) ions.
      Cross-linking gives the material sufficient spatial integrity to allow a
      holographic image to be recorded, while maintaining adequate porosity and
      elasticity of the polymer matrix for sensing applications. The new material has
      been characterized with respect to its response to pH and compared with a
      traditional gelatin holographic film. The response to some ions and small
      molecules typically found in analytical samples has also been measured.
      Functional groups introduced covalently into the poly(vinyl alcohol) matrix
      transform the base matrix into a pH-responsive polymer with predictable swelling
      properties and which can be further derivatized to incorporate specific ligands.
      A rationally designed holographic sensor for trypsin has been developed from
      chemically synthesized artificial polymers. A trypsin substrate, the poly(amino
      acid) poly(L-lysine), was incorporated into poly(vinyl alcohol) holograms to
      create a 'designed' holographic material which was degraded in a concentration
      dependent manner by trypsin. Extensions of this approach to other hydrolytic
      enzymes are briefly discussed.

PMID- 10076833
TI  - Development of a capacitive immunosensor: a comparison of monoclonal and
      polyclonal capture antibodies as the primary layer.
AB  - There is widespread interest in capacitance immunosensor systems which directly
      detect antigen binding to immobilized antibody. Our system comprises an active
      biolayer of antibodies bound to a silicon--silicon dioxide--silicon nitride (Si
      SiO2-Si3N4) surface. As with other groups, our system initially gave poorly
      reproducible responses on addition of antigen. We mechanically degraded the Si
      SiO2-Si3N4 surface, and the responses on addition of transferrin were monitored.
      The mechanical degradation allowed the affinity reaction to be 'seen'
      capacitively. Once the system was established, a comparison of capture antibodies
      was performed to establish the most effective biolayer. Three affinity reactions
      were examined: (a) 1D2A4, monoclonal antibody (mAb) to human transferrin, as the
      capture layer; (b) polyclonal goat anti-human transferrin antibody (PcAb) as the
      capture layer; and (c) 1D2A4 with transferrin (Tf) prebound as the capture layer.
      There was no response to addition of transferrin where 1D2A4 was the capture
      layer. Addition of transferrin when the polyclonal antibody was used as the
      primary layer resulted in a drop in measured capacitance. Addition of goat anti
      human transferrin antibody to a device with 1D2A4 plus transferrin as the capture
      layer also resulted in a measured capacitance decrease. There is a difference in
      dielectric/blocking effectiveness between the monoclonal and polyclonal
      antibodies.

PMID- 10076834
TI  - Electrochemical immunosensor for the detection of atrazine.
AB  - An amperometric immunosensor for the detection of the herbicide atrazine has been
      developed. A redox polymer PVPOs(bpy)2Cl was co-immobilized with the specific
      antibody on the surface of the electrode by crosslinking with PEGDGE to form an
      electron-conducting hydrogel. In a competitive assay the occurrence of the
      antibody-antigen reaction on the surface of the sensing film was detected through
      the 'electrical wiring' of the redox centres of antigen-labelled horseradish
      peroxidase and the electrode surface in the presence of H2O2 at 0.1 V
      (vsAg/AgCl).

PMID- 10076835
TI  - A flow immunoassay for studies of human exposure and toxicity in biological
      samples.
AB  - This paper describes a heterogeneous competitive flow immunoassay with a high
      sample throughput which can be used for the screening of smaller analytes in
      various samples. The method is based on off-line incubation of the analyte (Ag),
      a fluorescent labelled tracer (Ag*) and the corresponding antibody (Ab). The
      separation of bound (Ab-Ag*) and free tracer (Ag*) is based on a size exclusion
      and reversed phase mechanism utilizing a restricted access (RA) column. The
      column traps the free unbound tracer (Ag*) in its hydrophobic (C18) inner cavity
      but excludes the large Ab-Ag* complex, which is passed on and measured by the
      fluorescence detector. The flow immunoassay was developed using the triazine
      herbicide atrazine as a model compound owing to its human toxicity and widespread
      use. A sample throughput of 80 samples per hour and a detection limit of 300 pg
      ml-1 in water were obtained. Urine samples were successfully applied for direct
      injections into the flow system, while for human plasma samples an additional
      clean-up step using solid phase extraction was efficiently included where pure
      extract is obtained with the highly stable and biocompatible extracting column
      material. The resulting detection limits for atrazine in plasma and water samples
      using this clean-up and trace enrichment procedure were found to be 2 ng ml-1 and
      20 pg ml-1 respectively.

PMID- 10076836
TI  - Immunoreagents based on polymer dispersions for immunochemical assays.
AB  - Immunoreagents based on polymer dispersions consisting of unimodal polyacrolein
      (PAL) microspheres with diameters in the range 0.3-2.0 microns have been prepared
      and evaluated by various immunoassay techniques such as immunoradiometric assay
      of ferritin and microtitre particle agglutination and immunofiltration dot assay
      of group-specific polysaccharide of S. pyogenes (A-PS) in comparison with
      conventional carriers and methods. The antibodies were covalently or indirectly
      bound to the PAL. The coupled antibodies to ferritin retained a high average
      affinity (Ka = 4.5 x 10(9) M-1). In comparison with microcrystalline cellulose
      based immunosorbent, more than an order-of-magnitude lower amount of PAL-IgG was
      necessary for the analysis of ferritin. Use of PAL-IgG gave a higher sensitivity
      of assay with a detection limit of 0.7 x 10(-13) M l-1 and a wider concentration
      range of antigen detection (about four orders of magnitude) without manifestation
      of the high-dose hook effect. Particle agglutination assay of A-PS in microtitre
      plate was shown to be a simple, demonstrative and highly sensitive one-step
      analytical method with a detection limit of 0.05 ng A-PS/ml or 10(4) cells/ml.
      The sensitivity of immunofiltration assay using both enzyme and latex markers was
      shown to be approximately the same (50 ng A-PS/ml) and the duration of the assay
      was 3-5 min. No cross-reaction of latex conjugates with non-A Streptococcus cell
      lysates were observed.

PMID- 10076837
TI  - Studies of interactions with weak affinities and low-molecular-weight compounds
      using surface plasmon resonance technology.
AB  - Interactions between the immobilized weak-affinity monoclonal IgG antibody 39.5,
      which is specific for the glucose-alpha 1,4-glucose motif, and various
      oligosaccharides were studied with surface plasmon resonance technology. The
      antibody was immobilized at high levels on the surface of the sensor chip and
      different concentrations of the analytes were injected at 25 and 40 degrees C.
      The 39.5 antibody exhibited specific binding to maltose, tetraglucose and
      maltotriose, with dissociation constants Kd in the range from 0.07 mM (25 degrees
      C) to 1.0 mM (40 degrees C). Association and dissociation rate constants (ka and
      kd) were rapid and baseline was obtained almost immediately after the end of each
      antigen injection. This excluded the need for a regeneration step but also made
      calculation of the kinetic values impossible. Owing to the weak affinity and the
      small size of the analytes (< 1000 Da), a careful design of control surfaces is
      demanded to exclude artefactual results.

PMID- 10076838
TI  - Detection of low-molecular-weight heparin oligosaccharides (Fragmin) using
      surface plasmon resonance.
AB  - During the last decades there has been a growing realization of the central
      biological role that oligosaccharides and oligosaccharide-protein interactions
      play. One of the most striking examples is the use of heparin and low-molecular
      weight heparin oligosaccharides (Fragmin) to modify blood coagulation. Several
      monoclonal antibodies directed against glycosaminoglycan structures have been
      produced. However, their clinical use is limited by the difficulty of detection
      systems for oligosaccharides. In the present study we used a monoclonal antibody
      directed against heparin oligosaccharides prepared by partial nitrous acid
      deamination of heparin. Using a biosensor (BIAcore), purified antibody was
      immobilized on sensor surfaces and binding of oligosaccharide was measured by
      surface plasmon resonance. Using this technique, it was possible to quantitate
      low-molecular-weight heparin oligosaccharides in nanomolar concentrations.

PMID- 10076839
TI  - New approaches for the analysis of molecular recognition using the IAsys
      evanescent wave biosensor.
AB  - Trends in the analysis of molecular recognition using the IAsys evanescent wave
      biosensor are outlined. Diversification of sensor surface chemistry, an open
      cuvette format and the advent of robotics controlled by intelligent software are
      widening the range and throughput of applications. Analyses of binding and
      dissociation are now carried out across a wide spectrum of biomolecules,
      including protein, nucleic acid, carbohydrate and lipid. Determinations are
      obtained from a range of experimental formats. These include qualitative 'yes/no'
      screening assays, through semi quantitative ranking of kinetic association,
      dissociation and equilibrium constants for a family of binding partners, to
      deriving constants comparable with those which would be obtained in free
      solution. A dependence of the initial rate of biomolecular association on
      concentration allows analyte concentration to be measured--an increasingly common
      application class. This is often employed in situations where a rapid
      determination is required The ability to recover bound analyte from the sensor
      surface in sufficient amounts for subsequent characterization is opening up new
      routes to the parallel analysis of structure and function.

PMID- 10076840
TI  - High-density immobilization of an antibody fragment to a carboxymethylated
      dextran-linked biosensor surface.
AB  - There are numerous chemical methods published that enable protein coupling to
      carboxymethyl (CM) dextran. Here we have taken traditional amine coupling using N
      hydroxysuccinimide (NHS) and N'-(3-dimethylaminopropyl) carbodiimide
      hydrochloride (EDC) and coupled an antibody fragment (scFv) to CM dextran at a
      very high density. Using an upgraded BIAlite from Biacore AB, more than 7000 RU
      of scFv was coupled to a CM dextran biosensor chip. In addition, scanning
      electron microscopy was performed on CM dextran biosensor chips following amine
      coupling of 30 nm gold anti-IgG particles. This showed that amine coupling was
      uniform across the biosensor chip surface. Calculations show that 7620 RU of an
      scFv coupled to such a surface results in a mean distance between binding sites
      of 8.8 nm. This equates to a packing volume of approximately 20% of the available
      space occupied by the antibody fragment. Comparisons made with densities of
      covalently coupled IgG show that a greater number of antibody fragment molecules
      can be coupled per unit area. This is most likely due to the smaller size of an
      antibody fragment (scFv), which has a volume of less than 20% of an IgG molecule.
      The significance of these findings is discussed.

PMID- 10076841
TI  - Thermodynamic analysis of protein interactions with biosensor technology.
AB  - A methodology using biosensor technology for combined kinetic and thermodynamic
      analysis of biomolecular interactions is described. Rate and affinity constants
      are determined with BIAcore. Thermodynamics parameters, changes in free energy,
      enthalpy and entropy, are evaluated from equilibrium data and by using rate
      constants and transition state theory. The methodology using van't Hoff theory
      gives complementary information to microcalorimetry, since only the direct
      binding is measured with BIAcore whereas microcalorimetry measures all
      components, including e.g. hydration effects. Furthermore, BIAcore gives
      possibilities to gain new information by thermodynamic analysis of the rate
      constants.

PMID- 10076842
TI  - Affinity precipitation of proteins: design criteria for an efficient polymer.
AB  - Affinity precipitation is fast emerging as a successful technique for the
      purification of proteins which can be introduced at an early stage of downstream
      processing. The technique applies the use of reversibly soluble-insoluble
      polymers which have either natural or synthetic origin. Apart from the successful
      use of some natural polymers, such as chitosan and alginate, the vast application
      of the technique depends upon the design of efficient synthetic polymers. In this
      laboratory, N-isopropylacrylamide (NIPAM) copolymers have been developed for
      metal chelate affinity precipitation of proteins. The copolymers of 1
      vinylimidazole (VI) and iminodiacetic acid (IDA) with NIPAM were synthesized. The
      copolymers were thoroughly characterized with a view to designing an efficient
      soluble-insoluble polymer for metal chelate affinity precipitation of proteins.

PMID- 10076843
TI  - The use of affinity adsorbents in expanded bed adsorption.
AB  - The potential for the use of affinity ligands in expanded bed adsorption (EBA)
      procedures is reviewed. The use of affinity ligands in EBA may improve its use in
      direct recovery operations, as the enhanced selectivity of the adsorbent permits
      selective capture of the target from complex feedstocks and high degrees of
      purification. The properties of ligands suitable for use in EBA processes are
      identified and illustrated with examples. In addition to its use in the recovery
      of soluble products, such as proteins and nucleic acids, from particulate
      feedstocks, EBA can also be used to recover particulate entities, such as cells
      and packaged DNA (viruses and phages), from feedstocks. Affinity ligands coupled
      to appropriate chosen support materials will be required for such processes in
      order to achieve the necessary selectivity for the required particulate entity.
      The latter point is illustrated by the use of proteinaceous ligands immobilized
      to perfluorocarbon emulsions to achieve separations of microbial cells.

PMID- 10076844
TI  - Selective adsorption of endotoxin inside a polycationic network of flat-sheet
      microfiltration membranes.
AB  - For the removal of remaining amounts of endotoxin, sorbents with high selectivity
      for endotoxin are required. Typically, particulate sorbents with positively
      charged ligands, such as histidine, polymyxin B poly-L-lysine and
      poly(ethyleneimine) (PEI), display moderate to high removal efficiencies in an
      environment of low ionic strength. It was found that polycationic ligands are
      most suitable to meet an endotoxin concentration which is below the threshold
      level required for parenteralia. Furthermore, protein recoveries close to 100%
      are obtained if the decontamination is performed at a pH close to the pI of
      acidic proteins. The high selectivity is probably caused by complexation of the
      polycationic ligand with the polyanionic endotoxin, leading to interactions with
      KD < 10(-9) M using PEI and assuming M(r) = 10 kDa for monomeric endotoxin; with
      BSA the same ligand reveals only KD = 4 x 10(-6) M. Using polymer-coated
      microfiltration membranes, immobilization of positively charged ligands leads to
      membrane adsorbers which are generally superior to chromatographic adsorbers and
      allow faster processing. Since immobilization takes place at polymer chains, low
      molecular-weight ligands mainly add positive charges to the hydrophilic polymer.
      Consequently, membrane adsorbers with low-molecular-weight ligands, even DEAE,
      demonstrate similar selectivity to PEI or poly-L-lysine.

PMID- 10076845
TI  - Affinity-based in situ product removal coupled with co-immobilization of oily
      substrate and filamentous fungus.
AB  - In situ product removal (ISPR) involves actions taken for the fast removal of a
      product from the producing cell. ISPR is implemented to improve yield and
      productivity via minimization of product inhibition, minimization of product
      losses due to degradation or evaporation, and reduction of the number of
      subsequent downstream processing steps. Here we describe the implementation of
      affinity-based, specific ISPR as a crucial component of an integrative approach
      to problems associated with the biocatalytic production of a product exhibiting
      poor water solubility from an oily, water-insoluble precursor. Our integrative
      ISPR-based approach consists of co-immobilization of the oily substrate emulsion
      and the biocatalyst within bilayered alginate beads. A particulate-specific
      adsorbent, exhibiting high binding capacity of the product, is suspended in the
      reaction medium with periodical replacements. According to this approach, ISPR
      implementation is expected to shift the equilibration of product distribution
      between the co-immobilized oily substrate and the outer medium via specific
      product immobilization onto the added adsorbent. The product may subsequently be
      readily recovered via single-step final purification. This integrative approach
      was successfully demonstrated by the affinity-based ISPR of gamma-decalactone (4
      decanolide). gamma-Decalactone was produced from castor oil via its beta
      oxidation by the filamentous fungus Tyromyces sambuceus, co-immobilized with
      emulsified substrate within bilayered alginate beads. Product immobilization onto
      medium-suspended epichlorohydrin-crosslinked beta-cyclodextrin resulted in higher
      yield and easy pure product recovery.

PMID- 10076846
TI  - Affinity precipitation of concanavalin A--studies of some underlying mechanisms
      using dynamic laser light scattering.
AB  - The final outcome of an affinity precipitation process will depend upon the
      efficiency of each individual stage involved: the formation of initial affinity
      complexes, the build-up of a precipitate and the elution of the target protein.
      Investigations on the first stage were done in this study utilizing a model
      system. The target protein was the lectin concanavalin A (Con A). Eudragit S-100,
      a reversibly soluble/insoluble polymer consisting of methyl methacrylate and
      methacrylic acid, to which the affinity ligand p-aminophenyl-alpha-D
      glucopyranoside was coupled, served as the bifunctional ligand (ligand-Eudragit).
      Owing to the tetrameric structure of Con A, where each subunit has the ability to
      bind one sugar moiety, and to the multivalency of ligand-Eudragit, a network was
      formed between the Con A and ligand-Eudragit. It was possible to detect the
      initial soluble complexes formed by dynamic laser light scattering (DLLS) long
      before any precipitate could be analysed by transmittance measurements. The rate
      of complex formation was highly dependent on the ratio between lectin and ligand
      Eudragit. It was further shown that the system did not reach equilibrium within
      the 110 min studied. When the complex formation was studied in the presence of
      glucose, the build-up rate was decreased to different degrees depending on the
      sugar concentration used. At high glucose concentrations the complex formation
      was completely inhibited.

PMID- 10076847
TI  - Preliminary studies on the purification of a monoclonal antibody by affinity
      precipitation with Eudragit S-100.
AB  - A simple procedure for the purification of an IgG-type monoclonal antibody by
      affinity precipitation using Eudragit S-100 is presented. The ligand, a microbial
      lipase previously used as antigen, was coupled to the polymer at a concentration
      of 40 mg lipase/g Eudragit. This macroligand was reversibly precipitated by
      manipulating the pH at values higher and lower than 4.8. The effects of polymer
      concentration and dilution of hybridoma culture supernatant on the overall
      precipitation process were evaluated. The best purification factor was achieved
      with a polymer concentration of 0.1% (w/v) and a supernatant dilution of 1:3. The
      preliminary studies reported here enabled the purification of a monoclonal
      antibody in one step with an activity yield (by ELISA) of 50%-55% and a
      purification factor of ca 6.

PMID- 10076848
TI  - A synthetic ligand for IgA affinity purification.
AB  - We reported previously that TG19318, a synthetic ligand deduced from the
      screening of combinatorial libraries, displays specific and selective recognition
      properties for immunoglobulins of the G class and can be used conveniently for
      affinity chromatography purification of monoclonal and polyclonal antibodies. In
      this study we have extended the ligand characterization, examining its ability to
      bind IgA from cell culture supernatants and from IgG-deprived serum. Affinity
      columns prepared by immobilizing TG19318 on Sepharose allowed convenient one-step
      purification of monoclonal IgA directly from crude feedstocks, in high yield and
      with full recovery of immunoreactivity. Optimal column adsorption occurred with
      phosphate buffer at neutral pH, while elution of adsorbed IgA could be
      accomplished by a buffer pH change to acidic or basic conditions. Column capacity
      was close to 7 mg IgA/ml support.

PMID- 10076849
TI  - Affinity purification of mouse monoclonal IgE using a protein A mimetic ligand
      (TG19318) immobilized on solid supports.
AB  - A synthetic ligand (TG19318), deduced from the screening of a combinatorial
      peptide library, has been previously characterized by our group for its
      applicability in affinity chromatography for polyclonal and monoclonal IgG
      purification from crude sources. In this study we have extended the
      characterization of its recognition properties for other immunoglobulin classes,
      evaluating its ability to purify mouse monoclonal IgE from ascitic fluid. TG19318
      affinity columns proved useful for a very convenient one-step purification of IgE
      directly from crude ascites, by loading the samples on the columns equilibrated
      with 50 mM sodium phosphate at pH 7 and eluting and adsorbed IgE by a buffer
      change to 0.1 M acetic acid. Antibody purity after affinity purification was very
      high and no albumin traces were detected, as determined by SDS-PAGE analysis.
      Antibody activity was fully recovered after purification, as determined by
      immunoassays on antigen-coated plates, and up to 5 mg of IgEs could be purified
      on a 1 ml column in a single run.

PMID- 10076850
TI  - Purification of supercoiled plasmid DNA using chromatographic processes.
AB  - The interest in purifying injectable-grade plasmid DNA has increased with the
      development of gene therapy and DNA vaccination technologies. In this paper we
      develop a method for purifying a 4.8 kb plasmid based on chromatographic
      processes. An NaCl gradient was optimized on a Q Sepharose column and plasmid was
      eluted at 800-820 mM NaCl in a broad peak. Supercoiled plasmid was isolated after
      a final Sepharcryl S1000 SF gel filtration step. Final plasmid preparation was
      depleted of proteins and RNA, as revealed by the BCA assay and 1% agarose gel
      electrophoresis.

PMID- 10076851
TI  - Preliminary studies on continuous recovery and purification of the penicillin
      acylase under pseudo-affinity conditions using phenyl-Sepharose gel.
AB  - A continuous system for the recovery and purification of the penicillin acylase
      from crude extracts by recycling phenyl-Sepharose gel through three agitated
      vessels with disc filters of stainless steel is presented. The penicillin acylase
      present in the crude extract was absorbed into the phenyl-Sepharose gel under
      pseudo-affinity conditions (16% w/v of ammonium sulphate). After gel washing
      under the same conditions in the second vessel, enzyme desorption was performed
      using the same salt but at a lower concentration (6% w/v) in the third vessel.
      The preliminary studies reported here occurred without experimental difficulties,
      even at a gel concentration as high as 40% (v/v). The recovery of the penicillin
      acylase was achieved with high yield (74%), but a low purification factor of 2.4
      was obtained owing to the use of a crude extract with low specific activity.

PMID- 10076852
TI  - Protein displacement in dye-ligand chromatography using neutral and charged
      polymers.
AB  - Displacement chromatography was demonstrated to perform separations efficiently
      under mass-overloaded conditions, offering advantages such as increased product
      recovery and purity, superior resolving power, and concentration and purification
      in a single processing step. The use of water-soluble polymers for protein
      displacement in dye-ligand chromatography was initiated in our laboratory. The
      polymers for displacement were selected using differences spectroscopy to monitor
      their interactions with a dye-ligand in solution. Non-charged polymers such as
      poly(N-vinyl pyrrolidone) and poly(N-vinyl caprolactam) efficiently displaced
      lactate dehydrogenase from porcine muscle from a Blue Sepahrose column. The
      latter polymer, being thermosensitive, could be easily removed from the eluate
      and recovered by precipitation at 45 degrees C and low-speed centrifugation. The
      positively charged polymer poly(ethylene imine) proved to be an even more
      efficient displacer. The dye-ligand column could be regenerated after application
      of displacer either by washing with a solution of the soluble ligand Cibacron
      Blue (in the case of non-charged polymers) or by washing with highly alkaline
      solutions containing polyanions (in the case of poly(ethylene imine)) The latter
      formed a soluble complex with poly(ethylene imine) and stripped the column from
      the polymer.

PMID- 10076853
TI  - Unusual protein-binding specificity and capacity of aza-arenophilic gels.
AB  - A number of synthetic aza-arenophilic gels have been synthesized from Sepharose
      CL-4B, 3,5-dichloro-2,4,6-trifluoropyridine and 4-dimethylaminopyridine. These
      show high binding capacities for immunoglobulins and enzymes. Under high-salt
      buffer binding conditions, IgG can be effectively eluted, essentially free of
      contamination by BSA, using acidic conditions (pH 2.5) or phosphate buffers (pH
      7.4) containing nucleophiles. Enzymes can also be readily adsorbed and desorbed.
      Thus these gels can be reused as supports for the immobilization of enzymes.

PMID- 10076854
TI  - Cellulose powder from Cladophora sp. algae.
AB  - The surface are and crystallinity was measured on a cellulose powder made from
      Cladophora sp. algae. The algae cellulose powder was found to have a very high
      surface area (63.4 m2/g, N2 gas adsorption) and build up of cellulose with a high
      crystallinity (approximately 100%, solid state NMR). The high surface area was
      confirmed by calculations from atomic force microscope imaging of microfibrils
      from Cladophora sp. algae.

PMID- 10076855
TI  - Purification of substance P endopeptidase (SPE) activity in human spinal cord and
      subsequent comparative studies with SPE in cerebrospinal fluid and with
      chymotrypsin.
AB  - An enzyme activity capable of hydrolysing the neuroactive undecapeptide substance
      P (SP) between its Phe7-Phe8 residues was purified from the membrane-bound
      fraction of human spinal cords. The enzyme preparation yielded was compared with
      a previously described SP-hydrolysing enzyme from human cerebrospinal fluid (CSF)
      with regard to inhibition profile, protein chemical properties and kinetics. In
      addition, the results were compared with those of bovine pancreatic chymotrypsin
      (a serine protease that cleaves the carboxy-terminal side preferentially at
      hydrophobic amino acids). The SP peptidase activity was extracted from human
      spinal cords with 1% Triton X-100 in 20 mM Tris-HCI pH 7.8. After ion exchange
      chromatography (DEAE-Sepharose) where the enzyme activity was separated from
      other proteins by gradient elution, the pooled enzyme fraction was further
      purified by molecular sieving (Sephadex G-50). The enzyme activity was finally
      recovered by HPLC molecular sieving (Superdex 75 HR 10/30) using a new
      preparative system, AKTA-purifier, controlled by UNICORN software version 2.20.

PMID- 10076856
TI  - Direct measurement of intraparticle fluid velocity in superporous agarose beads.
AB  - Superporous agarose beads contain both normal diffusion pores and special, very
      wide superpores through which part of the chromatographic flow is transported, a
      situation that may greatly improve the chromatographic performance. For the first
      time such pore flow was measured directly by following the movement of
      microparticles (dyed yeast cells) through superporous beads packed in a
      chromatographic bed. The passage of the microparticles through the superpores and
      through the interstitial pores was recorded by a microscope/video camera. The
      video recordings were subsequently used to determine flow paths as well as the
      convective fluid velocities in both the superpores and the interstitial pores.
      The superpore fluid velocity was found to be proportional to the ratio between
      the squares of the respective pore diameters, which is in agreement with the
      Kozeny-Carman equation. Values for two-dimensional and three-dimensional
      tortuosity of the flow paths were measured and calculated respectively.

PMID- 10076857
TI  - Preparation of and optimal module housings for hollow fibre membrane ion
      exchangers.
AB  - Macroporous polyamide 6 hollow fibres can be polymer coated by a three-step
      procedure: first, reaction of the amino end groups with a bifunctional, double
      bond-containing reagent; second, block polymerization with different monomers;
      and third, polymer analogue reactions with amines or sulphite salts to produce
      ion exchanger groups. The densities of double bonds are dependent on the amino
      densities and are in the range of 20-30 mumol/g polyamide 6. The ion exchanger
      fibres were packed in different types of module housings to get an optimal
      separation unit. The best housing seems to be a so-called single-dead-end
      arrangement of fibres. Three types of ion exchanger hollow fibres have been
      produced: a weak and a strong anion exchanger and a strong cation exchanger. The
      dynamic protein-binding capacities are in the range of 40 mg/ml membrane. Using
      these membrane modules, it is possible to separate proteins in the same way as
      with particle-based ion exchangers. Fast protein separations with low pressure
      drop are possible.

PMID- 10076858
TI  - Role of 5-HT2A receptors in the stress-induced down-regulation of brain-derived
      neurotrophic factor expression in rat hippocampus.
AB  - Immobilization stress decreases the expression of BDNF mRNA in the rat
      hippocampus, and this effect could contribute to the atrophy of hippocampal
      neurons. This study examines the influence of selective 5-HT, as well as
      norepinephrine, receptor antagonists on the stress-induced down-regulation of
      BDNF mRNA. Pretreatment with a selective 5-HT2A receptor antagonist, MDL100,907,
      significantly blocked the influence of stress on expression of BDNF mRNA. In
      contrast, pretreatment with either a selective 5-HT2C or 5-HT1A receptor
      antagonist did not influence the stress-induced decrease in levels of BDNF mRNA.
      The stress-induced decrease was also not influenced by pretreatment with
      antagonists of beta(1/2)- or alpha1-adrenergic, or CRF-R1 receptors. The results
      demonstrate that 5-HT2A receptors mediate, at least in part, the stress-induced
      down-regulation of BDNF expression in the rat hippocampus.

PMID- 10076859
TI  - Internalization and resistance to degradation of Alzheimer's A beta 1-42 at
      nanomolar concentrations in THP-1 human monocytic cell line.
AB  - Microglial cell involvement in Alzheimer's disease has been related to amyloid
      beta (A beta) internalization, the release of inflammatory cytokines and the
      development of neuritic plaques. The human monocyte/macrophage THP-1 cell line
      has been widely used as a model of human microglial cells. We used THP-1 cells to
      study the adsorption, internalization and resistance to degradation of A beta1-40
      and A beta1-42 isoforms offered at nanomolar concentrations and free of large
      aggregates, conditions that may mimic a pre-fibrillar stage of A beta in the
      brain. Under these conditions, A betas did not induce THP-1 activation, as
      assessed by interleukin-1beta expression. A beta1-42 showed a preferential
      adsorption and intracellular accumulation as compared to A beta1-40, supporting
      that competent nuclei for A beta1-42 ordered aggregation may be formed inside
      microglial cells. In light of the possible neurotoxicity of soluble A beta1-42,
      we propose that amyloid formation within brain phagocytic cells may be a
      protective mechanism in early stages of the disease.

PMID- 10076860
TI  - Evidence for the presence of dopamine D1 receptor mRNA and binding sites in
      monkey amniotic epithelial cells.
AB  - In this study we examined the presence of dopamine D1 receptors in monkey
      amniotic epithelial cells (MAEC) using RT-PCR and radioligand binding
      experiments. We found that MAEC express D1 receptor mRNA that is having 99%
      homology with human dopamine D1 receptors. Saturation binding studies using
      [3H]SCH-23390 showed a high affinity D1 site with K(D) and Bmax values of 0.82 +/
      0.12 nM and 20.77 +/- 4.22 fmol/mg protein, respectively. Competition
      experiments showed that selective D1, but not D2, antagonists are potent
      displacers of [3H]SCH 23390 binding with a rank order of potency that is
      consistent with the pharmacology of the dopaminergic D1 site. These data provide,
      for the first time, compelling evidence that MAEC natively express D1 mRNA and
      binding sites and suggest that it may be a potential primate cell model to study
      D1 receptors and to explore new selective drugs active at these receptors.

PMID- 10076861
TI  - An endogenous MPTP-like dopaminergic neurotoxin, N-methyl(R)salsolinol, in the
      cerebrospinal fluid decreases with progression of Parkinson's disease.
AB  - There have been an increasing number of evidences indicating that dopamine
      derived N-methyl(R)salsolinol is an endogenous MPTP-like neurotoxin to cause
      Parkinson's disease. In the cerebrospinal fluid from newly diagnosed untreated
      patients with Parkinson's disease, the level of this toxin was found to increase
      significantly, compared to control and a disease control, multiple system
      atrophy. The effects of the disease duration and the medication on the level of N
      methyl(R)salsolinol were studied from the same patients. After about a 2-year
      period, the level was significantly reduced. The depletion of dopamine neurons by
      the disease progression may account for the reduction of the neurotoxin level,
      whereas L-DOPA therapy did not seem to affect the level of this toxin, even
      though the enhanced dopamine turnover. The results suggest that N
      methyl(R)salsolinol level in the cerebrospinal fluid may indicate remaining
      dopamine neurons in the parkinsonian brain.

PMID- 10076862
TI  - Effects of opioids on neuronal survival in culture of embryonic chick dorsal root
      ganglion neurons.
AB  - We studied the effects of endogenous and synthetic opioids on survival of primary
      cultured dorsal root ganglion neurons of 8-day chick embryos. In the basal growth
      medium containing nerve growth factor (NGF), [Leu5]enkephalin, [Met5]enkephalin
      or selective mu-agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) produced
      significant increase of neuronal survival in a naloxone-reversible manner. On the
      other hand, dynorphin A (1-13), [D-Pen2, L-Pen5] enkephalin (DPLPE) (a delta
      agonist) and U-50,488 (a kappa-agonist) showed no such effect. No viable neurons
      were observed in the absence of NGF in spite of the presence of any opioid
      peptides. These results suggest that [Leu5]enkephalin and [Met5]enkephalin might
      increase neuronal survival by stimulating mu-opioid receptors, and that these
      opioid peptides are working with other growth factors but, in and by themselves,
      do not promote survival.

PMID- 10076863
TI  - Optic target regulation of NADPH-diaphorase by larval retinal axons in
      Drosophila.
AB  - Development of the visual system in Drosophila requires the establishment of
      precise retinotopic connections between photoreceptors and their synaptic targets
      in the central nervous system. Nitric oxide (NO) has been implicated as a
      candidate signal involved in the establishment of retinal projection patterns. In
      this study the expression of NADPH-diaphorase in the lamina of Drosophila, and by
      implication nitric oxide synthase (NOS), was investigated in larvae with varying
      degrees of retinal innervation. NADPH-diaphorase expression was seen to increase
      in the lamina and eye disk following retinal neuronal death in eye specific pro
      apoptotic larvae (pGMR-hid) compared to wild type larvae, and was lower in the
      lamina in absent or reduced retinal innervation mutants (eyes absent and sine
      oculis). Retinal innervation is seen to regulate the expression of NADPH
      diaphorase expression in target structures.

PMID- 10076864
TI  - Effect of salmon-calcitonin on the analgesic effect of selective mu, delta and
      kappa opioid agonists in mice.
AB  - The analgesic effect of three different opioid agonists, DAMGO ([D-Ala2,N-Me
      Phe4,Gly5-ol]enkephalin), U-50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidynyl)cyclohexyl] benzene-aceramide methane sulphonate), and [D,Pen2
      D,Pen5]-enkephalin, which act upon mu, delta and kappa opioid receptors,
      respectively, was compared in the presence and absence of salmon-calcitonin (s
      CT). The analgesic test used was the writhing test in mice. The analgesic effect
      of the opioids was significantly enhanced by pretreatment of the animals with s
      CT intraperitoneally (i.p.) administered. This effect was more evident for the
      delta and kappa-agonists. The present result suggests that the joint
      administration of s-CT and opioids may be a useful and interesting alternative in
      the treatment of painful diseases resistant to other treatments.

PMID- 10076865
TI  - The neurotrophins NGF and NT-3 reduce sensory neuronal loss in adult rat after
      peripheral nerve lesion.
AB  - The effect of three different neurotrophins on axotomy-induced death of adult rat
      sensory neurons was examined. The ventral branch of the 13th spinal nerve was
      transected and the corresponding neurons in the 13th thoracic (T13) dorsal root
      ganglion (DRG) were pre-labelled with Fast Blue (FB). For a period of 4 weeks,
      animals received either no treatment, continuous intrathecal infusion of
      phosphate buffer, nerve growth factor (NGF), neurotrophin-3 (NT-3), or brain
      derived neurotrophic factor (BDNF). Labelled neurons remaining after this period
      were counted. Inert, or no treatment, resulted in extensive loss of the DRG
      neurons. BDNF application was virtually non-effective, while NGF or NT-3 resulted
      in a greater number of FB-labelled neurons compared to normal controls. This
      suggests that NGF and NT-3 are survival factors for adult sensory neurons with a
      therapeutic potential in peripheral nerve injuries.

PMID- 10076866
TI  - Oxidative stress is attenuated in mice overexpressing BCL-2.
AB  - The protooncogene Bcl-2 inhibits apoptosis in neural cells, which may involve
      mitochondrial stabilization and decreased generation of reactive oxygen species.
      Using in vivo microdialysis we found that following administration of the
      mitochondrial toxin 3-nitropropionic acid (3-NP) there was a significant increase
      in the conversion of 4-hydroxybenzoic acid (4-HBA) to 3,4-dihydroxybenzoic acid
      (3,4-DHBA) in control mice, but not in Bcl-2 overexpressing mice. Striatal
      lesions were observed in littermate control mice, whereas, lesions were minimal
      or absent in Bcl-2 overexpressing mice. This shows that Bcl-2 overexpression in
      vivo attenuates the generation of reactive oxygen species.

PMID- 10076867
TI  - Effects of presenilin N-terminal fragments on production of amyloid beta peptide
      and accumulation of endogenous presenilins.
AB  - To clarify the effects of the proteolytic cleavage of presenilin 1 (PS1) and
      presenilin 2 (PS2) proteins on their functions, we established stable cell lines
      which expressed the physiologically cleaved N-terminal fragment (NTF) with or
      without mutations of familial Alzheimer's disease (FAD). We found that exogenous
      expression of the PS1-NTF or PS2-NTF harboring FAD mutations was insufficient for
      increased production of amyloidogenic A beta X-42 peptide and that the
      overexpressed NTFs had no effect on the accumulation of endogenous presenilin
      fragments.

PMID- 10076868
TI  - Heatstroke induces c-fos expression in the rat hypothalamus.
AB  - We induced heat stress in urethane-anesthetized rats (the animals were exposed to
      an ambient temperature at 42 degrees C), and monitored their colon temperature,
      mean arterial pressure and local cerebral blood flow. Rats 0, 20, 40 or 80 min
      after heat stress were sacrificed for determination of c-fos mRNA and protein
      expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and
      preoptic nucleus (PON). The heatstroke, which appears as profound decreases in
      both mean arterial pressure and local cerebral blood flow and increases in colon
      temperature, is produced 80 min after heat stress. We show the c-fos mRNA and
      protein is strongly induced in all these nuclei of rat hypothalamus after the
      onset of heatstroke. We conclude that c-fos expression in the hypothalamus during
      rat heatstroke is associated with hyperthermia, arterial hypotension and cerebral
      ischemia.

PMID- 10076869
TI  - Synthesis of long trinucleotide repeats in vitro.
AB  - More than a dozen diseases have been associated with the expansion of
      trinucleotide repeats. Most of these expanding repeats are GC-rich (CGG/CCG or
      CTG/CAG), but it is difficult to amplify GC-rich repeat DNA from patient samples
      by the polymerase chain reaction. We invented a pair of methods to synthesize
      long trinucleotide repeats in vitro by polymerase extension utilizing a thermal
      cycler. A combination of the two methods, termed the non-template PCR method and
      SLIP (Synthesis of Long Iterative Polynucleotide) method, produced (CTG/CAG)190
      repeat DNA. We expect that these two methods will contribute to studies of all
      diseases associated with tri-nucleotide repeat expansion, since they can be
      applied to any type of repeat DNA.

PMID- 10076870
TI  - Differential expression of sialoglycoproteins in the rat hippocampus and its
      changes during aging.
AB  - The distribution pattern of sialylated glycoproteins in the hippocampal formation
      of 9-week-old and 29-month-old rats was examined using Maackia amurensis lectin,
      specific for Sia alpha2-3Gal, and Sambucus sieboldiana agglutinin specific for
      Sia alpha2-6Gal(GalNAc), and a monoclonal antibody for a linear homopolymer of
      alpha2-8-linked sialic acid. Each lectin and antibody showed different and
      characteristic staining patterns. On comparison of younger and older animals,
      different staining patterns were revealed. These results indicate that
      sialoglycoproteins with different sialyl linkages were expressed in distinct
      regions of the rat brain and their expression patterns changed with aging.

PMID- 10076871
TI  - Characterization of absence seizure-dependent cyclic AMP responsive element-and
      activator protein 1 DNA-binding activities in lethargic (lh/lh) mice.
AB  - The characterized nuclear cyclic AMP responsive element (CRE)- and activator
      protein 1 (AP-1) DNA-binding activities in various brain regions of lethargic
      (lh/lh) mice, a genetic model of absence seizures. Gel-shift assays showed that
      nuclear CRE- and AP-1 DNA-binding activities in the thalamus and cerebral cortex,
      but not in other regions such as the hippocampus and cerebellum of lethargic mice
      were significantly higher than those of non-epileptic control mice. Furthermore,
      CRE- and AP-1 DNA-binding activities in lethargic mice, but not control mice,
      were inhibited by the specific GABA(B) receptor antagonist CGP 46831, at a dose
      which suppressed seizure behavior and spike and wave discharges. These results
      suggest that enhanced nuclear CRE- and AP-1 DNA-binding activities in the
      thalamocortical region are related to generation and/or propagation of absence
      seizures in lethargic mice.

PMID- 10076872
TI  - Delayed neuronal cell death in the rat hippocampus is mediated by the mitogen
      activated protein kinase signal transduction pathway.
AB  - Transient global ischemia caused by 5 min of cardiac arrest induced delayed
      neuronal cell death (apoptosis) in the CA1 region of the rat hippocampus. To
      characterize the molecular mechanisms that regulate apoptosis in vivo, the
      contributions to cell death of mitogen-activated protein kinase family members
      were examined in the hippocampal region after brain ischemia-reperfusion.
      Ischemia-reperfusion led to a strong activation of the JNK/SAPK (c-Jun NH2
      terminal protein kinase/stress activated protein kinase), ERK (extracellular
      signal-regulated kinase), and p38 enzymes. These results with other previous
      studies suggest that the activation of JNK/SAPK in accordance with p38
      contributes to the induction of apoptosis in CA1 neurons.

PMID- 10076873
TI  - Anticipatory coping of pain expressed in the human anterior cingulate cortex: a
      positron emission tomography study.
AB  - We used positron emission tomography (PET) to monitor the regional cerebral blood
      flow (rCBF) as an index of brain activity in regions proposed to participate in
      affective-motivational and cognitive-evaluative dimensions of pain during
      anticipation of a noxious stimulation. Specifically we were interested in the
      anterior cingulate cortex (ACC), the ventromedial prefrontal cortex (VMPFC) and
      the periaqueductal grey (PAG). Anticipating an unpredictable and unlearned pain
      stimulus activated the right ACC, the VMPFC and the PAG while anticipating a
      learned pain-stimulus resulted in a decreased activity in the ACC and the VMPFC.
      These patterns are compatible with two facets of affect-laden cognitive coping:
      alertness and attention-distraction. The right-preponderant expression of the
      changes in the ACC supports the hypothesis of a preferential role of the non
      dominant hemisphere in negative emotional processing. The data demonstrate an
      anticipatory coping mechanism and illustrate a neurophysiological process
      underlying the modulation of attention to pain.

PMID- 10076874
TI  - Prodynorphin and proenkephalin mRNAs are increased in rat brain after acute and
      chronic administration of gamma-hydroxybutyrate.
AB  - The effects of gamma-hydroxybutyrate (GHB) on prodynorphin (PD) and proenkephalin
      (PE) mRNA expression were examined using in situ hybridization histochemistry in
      discrete rat brain structures rich in GHB receptors. A single dose of GHB (500
      mg/kg i.p.) increased striatal PE mRNA levels (+60%) between 15 and 90 min after
      injection. An increase in PD mRNA expression was observed in the frontal cortex
      (+90%) 6 h after GHB administration. Chronic exposure to GHB (500 mg/kg i.p.
      twice a day) for 10 days induced significant increases in both PE and PD mRNA
      levels in different brain regions examined, suggesting that PD and PE mRNA
      expressions are modulated by the endogenous GHBergic system.

PMID- 10076875
TI  - Kinesin cross-bridges between neurosecretory granules and microtubules in the
      mouse neurohypophysis.
AB  - Neurosecretory granules are conveyed along microtubules in the neurohypophysial
      axon. By both quick-freeze deep-etch and thin section electron microscopies, we
      found cross-bridges between the granules and microtubules. The length of the
      cross-bridges (mean 26.6 +/- 15.2 nm) was not uniform, and its histogram was
      multi-phasic showing the highest peak around 20 nm and several lower peaks in the
      range of 40-100 nm. This implies that cross-bridges are complexes of several
      kinds of constituents. Immunofluorescence microscopy showed the expression of a
      motor protein kinesin in the mouse neurohypophysis. Immunoelectron microscopy
      detected kinesin at the contact sites of neurosecretory granules to microtubules.
      These results suggest that kinesin is a major component of the cross-bridges, and
      involved in the neurosecretory granule transportation.

PMID- 10076876
TI  - Genetic drift. Just watching.

PMID- 10076877
TI  - Long-chain L 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency does not appear
      to be the primary cause of lipid myopathy in patients with Bannayan-Riley
      Ruvalcaba syndrome (BRRS).
AB  - In order to test the hypothesis that long-chain L 3-hydroxyacyl-coenzyme A
      dehydrogenase (LCHAD) deficiency is associated with the lipid myopathy and muscle
      carnitine deficiency observed in Bannayan-Riley-Ruvalcaba syndrome (BRRS), we
      studied the enzyme activity in cultured skin fibroblasts from three generations
      of a family with a clear dominant inheritance of BRRS. Enzyme activities were
      normal while the germline PTEN missense mutation P246L segregated with BRRS in
      this family. No PTEN mutations were identified in the original patient with BRRS
      and LCHAD deficiency. These data suggest that the previously reported case of
      LCHAD and BRRS either represents the coincidental concurrence of two rare genetic
      events or that a gene other than PTEN is related to LCHAD and BRRS.

PMID- 10076878
TI  - Two independent mutations in a family with neurofibromatosis type 1 (NF1).
AB  - We report on two independent alterations of the NF1 gene in a three-generation
      kindred with neurofibromatosis type 1 (NF1). Using temperature gradient gel
      electrophoresis (TGGE) in a mutation analysis of exon 31 of the NF1 gene we
      detected the previously reported nonsense mutation R1947X. This C-to-T transition
      at codon 1947 in exon 31 is considered to represent a mutation "hot spot" of the
      NF1 gene due to 5mCpG deamination. All living family members together with their
      genomic DNA were included in this investigation. However, the mutation R1947X was
      absent from two undoubtedly affected siblings of the propositus. Another NF1
      mutation (889-2A-->G) was identified in the two sibs by the protein truncation
      test (PTT). The novel splice site mutation 889-2A-->G results in a skip of NF1
      exon 7 during splicing and protein truncation due to frameshift. The two NF1
      alterations are linked to different paternal haplotypes. In our study of a three
      generation kindred, R1947X represents a de novo mutation whereas 889-2A-->G is an
      inherited splice mutation. Implications for phenotype variation are discussed.

PMID- 10076879
TI  - VACTERL as primary, polytopic developmental field defects.
AB  - Previously we proposed that the VACTERL association represents a dysmorphogenetic
      response of the primary developmental field, i.e., polytopic developmental field
      defects (DFD). As such, it should conform to the essential attributes of a DFD,
      namely, heterogeneity, homology, and phylogeneity. To study its heterogeneity, we
      analyzed the data of the Spanish Collaborative Study of Congenital Malformations
      (ECEMC). Our results confirm the observations indicating that the different
      patterns of defects that constitute this entity are not only clinically variable
      but also causally heterogeneous. This causal heterogeneity, which is of crucial
      importance in defining developmental fields, gives additional credence to the
      hypothesis that VACTERL constitutes a primary polytopic DFD.

PMID- 10076880
TI  - An autosomal dominant or X-linked osteodysplastic disorder with severe cervical
      involvement.
AB  - A disorder affecting bone and cartilage growth is described in a mother and her 3
      year-old son. A dysplastic process involving the vertebral bodies, most
      pronounced in the cervical region and leading to cervical dislocation in the
      first of these two patients, is the most significant complication of this
      disorder. This entity appears unrelated to other previously described skeletal
      dysplasias with cervical kyphosis as a major manifestation. This disorder is most
      likely autosomal dominant.

PMID- 10076881
TI  - X-linked Kallmann syndrome and renal agenesis occurring together and
      independently in a large Australian family.
AB  - Males with X-linked Kallmann syndrome (XLKS) may have renal agenesis. We studied
      a large kindred with a history of eight males affected by XLKS born in five
      generations. Their XLKS was shown to be due to an intragenic mutation of the KAL
      1 gene. We also documented three male neonatal deaths due to bilateral renal
      agenesis (BRA), five males with unilateral renal agenesis (URA), and one female
      with a pelvic ectopic kidney in this kindred. Of four XLKS males who had renal
      imaging studies, two had URA. The kindred's KAL-1 mutation was not present in
      three of the males with URA, the female with the ectopic kidney, nor in preserved
      autopsy tissue from one infant with BRA. The high frequency of renal agenesis in
      this family, in the presence and absence of the KAL-1 mutation, suggests an
      autosomal dominant or X-linked gene which may independently or co-dependently
      contribute to renal agenesis.

PMID- 10076882
TI  - Atelosteogenesis type III: long term survival, prenatal diagnosis, and evidence
      for dominant transmission.
AB  - We describe two additional instances of atelosteogenesis, type III, in a woman
      and her son. Clinical and radiographic information concerning these individuals
      allows further definition of this rare skeletal dysplasia. This is the first
      documentation of survival to adulthood of an individual with this disorder, of
      prenatal diagnostic assessment of an affected individual, and of vertical
      transmission suggestive of autosomal dominant inheritance. The clinical and
      radiologic phenotype of atelosteogenesis, type III overlaps with that of another
      skeletal dysplasia, autosomal dominant Larsen syndrome; these most likely
      represent allelic conditions.

PMID- 10076883
TI  - Methimazole embryopathy: delineation of the phenotype.
AB  - We report on a further case of congenital anomalies in a child exposed to
      methimazole during the first trimester of pregnancy (from first to seventh
      gestational week), and define a specific malformation pattern related to prenatal
      methimazole exposure and consisting of choanal and esophageal atresia, scalp
      defects, minor facial anomalies and psychomotor delay.

PMID- 10076884
TI  - Five familial cases of opsismodysplasia substantiate the hypothesis of autosomal
      recessive inheritance.
AB  - We describe a family with two marriages of first cousins and a total of five
      children with opsismodysplasia. The diagnosis was based on clinical,
      radiological, and immunhistochemical findings. Helpful to the diagnosis was the
      testing with type I collagen antibodies, showing abnormally high levels in the
      hypertrophic area of growth cartilage. This observation supports the hypothesis
      of autosomal recessive transmission of opsismodysplasia.

PMID- 10076885
TI  - From Horus the child to Hephaestus who limps: a romp through history.
AB  - The question of why Hephaestus, the Greek god of smiths, limped has been the
      subject of much debate, mainly on mythological grounds. This debate extended also
      into the field of medical diagnosis, with attempts at defining the nature of the
      deformity that made the crippled Hephaestus the buffoon of the other Olympic
      gods. One problem encountered in these debates was the changes to which the ugly
      young Hephaestus was subjected with the passing of time-from a limping deformed
      youth to the later dignified and normal man. While some authors, largely
      influenced by poetic Greek texts and vase paintings, attributed the limp to
      talipes (club-feet), others pointed to certain features suggestive of
      achondroplasia. Since the image of the early Hephaestus is based mainly on the
      much earlier concept of the Egyptian god Ptah, who as the triune god of the
      resurrection sometimes is depicted as an achondroplastic dwarf (Ptah-Pataikos),
      the suggestion of the possible achondroplastic dwarf-like nature of the early
      Hephaestus is not implausible. It is supported by similarities in the image of
      Hephaestus to some features in other Egyptian gods, such as the domestic god Bes,
      the guardian of the new-born, and the Horus the Child or Harpocrates (Greek), yet
      another protector of youth and "the symbol of everything that is young and
      vigorous" [Budge, 1969: The Gods of the Egyptians, or Studies in Egyptian
      Mythology. Volume I.]. The characteristic feature of this child-god is the "lock
      of Harpocrates" on the right side of his head. That this lock can sometimes also
      be seen not only on the head of Ptah-Pataikos and of Bes but also on the young
      Hephaestus is highly suggestive of the Egyptian influence on his image. Recently,
      however, another interesting explanation of Hephaestus's limp has been suggested
      that may explain why the Egyptian influenced image of the early achondroplastic
      Hephaestus changed to the later, more Grecian view of the smith-god who hobbled
      because of club-feet. Improvements in composition-analysis of samples from
      antique statues and various utensils have led to the suggestion that the
      introduction of new smelting techniques in antique times may have exposed ancient
      metal workers to the effects of various toxic metals causing, for instance,
      chronic lead poisoning or, more relevant here, chronic arsenic poisoning causing
      peripheral neuritis with weakness and lameness of one or both lower extremities.
      Later changes in smelting technique, and recognition or guess-work of a possible
      connection between these techniques and toxic effects, may explain the change
      from the buffoon-like achondroplastic walk to the club-footed limp and eventual
      normal behaviour of Hephaestus, the Smith. In other words: Did Hephaestus limp
      because of his arsen-neuritis?

PMID- 10076886
TI  - Patient described by Chun et al. may not present Antley-Bixler syndrome.

PMID- 10076887
TI  - Not Antley-Bixler syndrome.

PMID- 10076888
TI  - Maternal uniparental disomy of chromosome 21 in a normal child.
AB  - Maternal uniparental disomy of chromosome 21 [upd(21)mat] was found previously in
      a normal female and in 2 cases of early embryonic failure. We present a
      phenotypically normal child with upd(21)mat due to a de novo der(21;21)(q10;10).
      This finding suggests that chromosome 21 is not imprinted in the maternal
      germline.

PMID- 10076889
TI  - Expression of gicerin, a novel cell adhesion molecule, is upregulated in the
      astrocytes after hypoglossal nerve injury in rats.
AB  - Gicerin is an integral membrane glycoprotein which mediates cell-cell and cell
      extracellular matrix (ECM) interactions in the nervous system. We studied gicerin
      expression in the hypoglossal nucleus post transection using in situ
      hybridization and immunocytochemistry. We found that hypoglossal nerve injury
      resulted in a significant increase in gicerin expression. Its expression levels
      reached peak values in reactive astrocytes surrounding axotomized motoneurons of
      the ipsilateral hypoglossal nucleus 14 days after hypoglossal nerve injury. The
      results indicate that gicerin is up-regulated during nerve regeneration,
      suggesting that gicerin expressed in the reactive astrocytes might be involved in
      the processes of nerve regeneration.

PMID- 10076890
TI  - Altered conformation of recombinant frontotemporal dementia-17 mutant tau
      proteins.
AB  - Recently, a series of both non-coding (intronic) and coding (exonic) mutations in
      the tau gene have been linked to a family of autosomal dominant dementias
      referred to as frontotemporal dementia-17. While linkage analysis has
      demonstrated that these mutations segregate with disease in affected families, it
      is unclear how mutant tau proteins could lead to the degenerative cascade seen in
      frontotemporal dementia-17. The present study demonstrates that coding mutations
      of tau seen in frontotemporal dementia-17 exhibit altered physical and structural
      characteristics as determined by reverse phase high performance liquid
      chromatography and circular dichroism spectroscopy. These data suggest that the
      previously identified mutations in the tau gene seen in frontotemporal dementia
      17 are not merely benign polymorphisms, but may have functional consequences for
      microtubule binding, microtubule polymerization, and the abnormal aggregation of
      tau seen in a variety of neurodegenerative diseases.

PMID- 10076891
TI  - Rabbit experimental sensory ataxic neuropathy: anti-GD1b antibody-mediated trkC
      downregulation of dorsal root ganglia neurons.
AB  - We previously reported experimental sensory neuropathy in rabbit induced by the
      immunization of ganglioside GD1b. The major pathological change in diseased
      rabbits was degeneration of primary sensory neurons with central axons extending
      to the dorsal column of the spinal cord. The loss of primary sensory neurons that
      mediate proprioceptive sensation prompted us to investigate the expression of
      trkC in dorsal root ganglia (DRG) because this type of neuron is thought depend
      mainly on neurotrophin-3-mediated trkC signaling. Northern blotting analysis
      revealed markedly reduced expression of trkC in DRG of diseased rabbits in acute
      phase. This result together with the absence of lymphocytic infiltration in DRG
      of diseased rabbits at any stage suggests the anti-GD1b antibody-mediated
      downregulation of trkC expression could be one of the pathogenesis of this
      experimental sensory ataxic neuropathy.

PMID- 10076892
TI  - Orexin A-like immunoreactivity in the rat brain.
AB  - Distribution of orexin-A-like immunoreactivity (ORX-LI) in rat brains was
      investigated with the use of a rabbit polyclonal antibody against the full length
      peptide orexin A. Virtually all the ORX-LI cell bodies were observed in the
      lateral hypothalamus at the level of median eminence. The large majority of ORX
      LI neurons appeared spherical or fusiform, 20-30 microm in diameter and issued
      two to five cell processes with few secondary branchings. Numerous ORX-LI fibers
      were observed in subregions of the hypothalamus. ORX-LI cell processes were
      sparsely distributed in the cortex, hippocampus and thalamus. Many varicose ORX
      LI cell processes were situated close to the 3rd and lateral ventricles, some of
      which appeared to be protruding into the lumen. As a corollary, orexin A may be
      released into the ventricles and interact with neurons in distant targets, in
      addition to influencing the activity of neurons with which ORX-LI axons make
      synaptic contacts.

PMID- 10076893
TI  - Transplantation of glial cell progenitors from brains of normal rats and mice
      into brains of neonatal carbonic anhydrase II-deficient mutant mice.
AB  - Carbonic anhydrase II (CAII) is expressed in oligodendrocytes, astrocytes and
      myelin in brains of rats and normal mice, but not in the brains of CAII-deficient
      mutant mice. We have transplanted mixed glial-cell suspensions from normal mouse
      brains, and oligodendrocyte-enriched precursor cells cultured from normal rat
      brains, respectively, into the brains of neonatal CAII-deficient mutant mice.
      Some CAII-positive astrocytes and oligodendrocytes developed in the brains of the
      host CAII-deficient mice at 8, 14 and 18 days posttransplant (DPT). In
      transplants of either mixed glial cells or oligodendrocyte precursors, CAII
      positive oligodendrocytes were less plentiful than CAII-positive astrocytes and
      appeared to be less healthy. CAII-positive astrocytes developed by 8 DPT, and
      there were some oligodendrocytes in cerebral cortex at 14 DPT and in brainstem by
      18 DPT. The data suggested that if glial-cell progenitors were to be injected
      into demyelinated lesions, any oligodendrocytes descended from the donor would be
      accompanied by astrocytes also descended from donor cells.

PMID- 10076894
TI  - Brain potentials during mental arithmetic-effects of problem difficulty on event
      related brain potentials.
AB  - One addend '+' symbol and another addend were presented in sequence to subjects
      in a monitor, and event-related brain potentials (ERPs) were recorded at the same
      time to examine the effect of problem difficulty (with or without carrying in
      solution) on ERPs. After the presentation of the second addend, N1, P1, N2, late
      positive complex and slow waves were recorded. The P2 amplitude at F3 site for
      the difficult arithmetic problems between 168 and 184 ms is larger (more
      positive) than that for easy problems (P < 0.05). The mean latency of P2 at F7
      and P3b at F3 and F4 is significantly longer for difficult problems than that for
      easy ones (P < 0.05). It is suggested that prefrontal activity may be involved in
      the arithmetic data retrieval process. ERPs is modified to different degrees by
      changing the difficulty of mental arithmetic.

PMID- 10076895
TI  - Spinal integration of antidromic mediated cutaneous vasodilation during dorsal
      spinal cord stimulation in the rat.
AB  - The purpose of this study was to determine the involvement of supraspinal centers
      and spinal synaptic integration in cutaneous vasodilation mediated by dorsal
      spinal cord stimulation (DCS). Laser Doppler flowmetry was used to assess
      cutaneous blood flow changes in the rat hindpaw during DCS with a unipolar ball
      electrode placed at the L2-L3 spinal level. Results demonstrated that transecting
      the spinal cord at the T10 spinal segment did not alter the DCS response while
      T13 spinal transection abolished the DCS-induced vasodilation. Inhibition of
      synaptic activity with topical application of muscimol (0.2 mM) on the dorsal
      surface of the spinal cord markedly attenuated the DCS response. In conclusion
      DCS-induced vasodilation involved synaptic integration but did not require input
      from rostral spinal sites or supraspinal areas.

PMID- 10076896
TI  - Melatonin potentiates the GABA(A) receptor-mediated current in cultured chick
      spinal cord neurons.
AB  - The effect of melatonin on the gamma-aminobutyric acidA (GABA(A)) receptor
      mediated response was studied in cultured chick spinal cord neurons using the
      whole-cell voltage-clamp recording technique. Melatonin rapidly and reversibly
      potentiated the GABA-induced current in a dose-dependent fashion, with an EC50 of
      766 microM and a maximal potentiation of 148%. Potentiation of the GABA response
      by melatonin was mediated by increasing the potency of GABA rather than the
      efficacy. Prolonged exposure to a saturating concentration of the disulfide
      reducing agent dithiothreitol did not attentuate the effect of melatonin on the
      GABA response, indicating that melatonin does not act through the redox site.
      Furthermore, our results demonstrate that melatonin and 5alpha-pregnan-3alpha-ol
      20-one (a positive steroid modulator of the GABA(A) receptor) act through
      different sites.

PMID- 10076897
TI  - A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive
      dystonia.
AB  - Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the
      considerable heterogeneity of clinical phenotypic expression. To explain the
      clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH
      G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than
      an unaffected heterozygote. Coexpression experiments using the mutant with wild
      type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent
      manner, suggesting that the dominant negative effect of a mutant GCH on the
      normal enzyme might be one of the molecular mechanisms for the clinical
      heterogeneity of DRD.

PMID- 10076898
TI  - The GABA(C) receptor is present in cone-horizontal cell axon terminals isolated
      from catfish retina.
AB  - Whole cell voltage-clamp recordings were performed on isolated terminals and
      somata from catfish retina to compare the distribution of excitatory and
      inhibitory receptors in both structures. Saturating concentrations of glutamate
      or kainate produced small currents in axon terminals, averaging less than 8% of
      the current evoked in the soma. In contrast, application of high concentrations
      of gamma-aminobutyric acid (GABA) produced approximately similar current
      amplitudes in both structures. Based on estimates of membrane surface area, GABA
      induced current densities were around 0.05 pA/microm2 for both structures. The
      GABA-activated current in the axon terminal was not blocked by bicuculline or
      SR95531, but was completely inhibited by picrotoxin. Baclofen did not mimic the
      GABA effect, but trans-4-aminocrotonic acid (TACA, 300 microM) and muscimol (1
      mM) elicited currents of 100 and 40 pA, respectively. These results suggest that
      the axon terminals of cone-horizontal cells possess GABA(C) receptors at a high
      density, do not possess GABA(A) or GABA(B) receptors, and have few glutamate
      receptors. The GABA(C) receptors could function as postsynaptic receptors in the
      inner plexiform layer or as autoreceptors.

PMID- 10076899
TI  - Power of theta waves in the EEG of human subjects increases during recall of
      haptic information.
AB  - Several studies have reported a functional relationship between spectral power
      within the theta-band of the EEG (theta-power) and memory load while processing
      visual or semantic information. We investigated theta power during the processing
      of different complex haptic stimuli using a delayed recall design. The haptic
      explorations consisted of palpating the structure of twelve sunken reliefs with
      closed eyes. Subjects had to reproduce each relief by drawing it 10 s after the
      end of the exploration. The relationship between mean theta power and mean
      exploration time was analysed using a regression model. A linear relationship was
      found between the exploration time and theta power over fronto-central regions
      (Fp1, Fp2, F3, F7, F8, Fz, C3) directly before the recall of the relief. This
      result is interpreted in favour of the hypothesis that fronto-central theta power
      of the EEG correlates with the load of working memory independent of stimulus
      modality.

PMID- 10076900
TI  - Apolipoprotein E genotype does not affect the age of onset of dementia in
      families with defined tau mutations.
AB  - We have assessed whether apolipoprotein E (ApoE) genotype influences the age of
      onset of dementia in a series of families with frontal temporal dementia with
      defined mutations in the tau gene. In contrast to the situation in Alzheimer's
      disease (AD), we could find no evidence that the age of onset of disease was
      influenced by the ApoE genotype.

PMID- 10076901
TI  - Increase in fiber density for immunoreactive serotonin, substance P, enkephalin
      and thyrotropin-releasing hormone occurs during the early presymptomatic period
      of motoneuron disease in Wobbler mouse spinal cord ventral horn.
AB  - The Wobbler mouse is a useful small animal model for the study of human
      motoneuron diseases. Besides showing the loss of motoneurons when the symptoms
      are expressed around the age of 3 weeks, we have also demonstrated the presumed
      'sprouting' of neuronal processes in the cervical spinal ventral horn which
      contain immunoreactive (IR) serotonin (5-HT), substance P (SP) and methionine and
      leucine enkephalins (ME, LE), as well as thyrotropin-releasing hormone (TRH).
      This occurs during the symptomatic period when IR-5-HT, ME and LE sprout at Stage
      1, around the age of 3 weeks, whereas IR-SP sprouts only at a late stage (stage
      4) of the disease (at age 3 months). The present investigation shows that the
      presumed sprouting occurs even before the appearance of symptoms and prior to
      significant motoneuron losses. IR-5-HT containing neuronal processes sprout by
      postnatal day 7, whereas IR-SP, -ME, -LE, and -TRH processes sprout by day 14.
      Hypothetically the early sprouts may contribute to the loss of motoneurons. They
      also respond to ciliary and brain derives neurotrophic factors cotreatment. IR-SP
      neuronal processes, although they sprout by day 14, show normal fiber density by
      the time symptoms appear (stage 1, age 21 days). However the SP sprouting is
      biphasic and a significant increase in number also occurs at an advanced stage of
      the disease (stage 4, age 3 months).

PMID- 10076902
TI  - Effects of experimental hypercapnia on hippocampal long-term potentiation in
      anesthetized rats.
AB  - The effects of hypercapnia, which has been reported to impair consciousness, on
      the long-term potentiation of the population spike in the CA1 pyramidal cell of
      the hippocampus in anesthetized rats were studied. Experimental hypercapnemia was
      induced by inspired 13% CO2 with 21% O2. Arterial blood gas analysis after 80 min
      inspired 13% CO2 showed pH 7.08+/-0.05, PCO2 = 104.09+/-12.86 mmHg, PO2 = 90.71+/
      18.89 mmHg, BE -4.64+/-2.97 (mean +/- SD, n = 18). Inspired 13% CO2 reduced the
      amplitude of the population spike to 50% of the baseline. After delivery of
      tetanic stimulation (400 Hz, five bursts of eight pulses, inter-burst interval 1
      s) population spike height was enhanced to pre-tetanic levels. Withdrawal of
      inspired CO2 unmasked an increase in population spike amplitude. These findings
      suggest that acute retention of carbon dioxide, which is designated as pure
      hypercapnemia without hypoxemia, may suppress hippocampal synaptic transmission
      but not its plasticity.

PMID- 10076903
TI  - Increase in oxidized NO products and reduction in oxidized glutathione in
      cerebrospinal fluid from patients with sporadic form of amyotrophic lateral
      sclerosis.
AB  - To determine the role of free radical mechanisms in the pathogenesis of
      amyotrophic lateral sclerosis (ALS), cerebrospinal fluid concentrations of
      oxidized nitric oxide (NO) products (nitrite and nitrate) and reduced and
      oxidized forms of glutathione (GSH and GSSG, respectively) were compared between
      patients with the sporadic form of ALS (SALS) and controls. In the SALS patients,
      the nitrate levels were significantly higher (by 73%) in contrast to remarkably
      lower GSSG/GSH ratio, approximately 3-fold, compared to controls. These results
      suggest that NO production or oxidation is activated in SALS patients, leading to
      a decrease in superoxide radicals to oxidize GSH. The subsequent generation of a
      highly reactive anion, peroxynitrite, may play a causal role in the pathogenesis
      of SALS.

PMID- 10076904
TI  - Local expression of inducible nitric oxide synthase in an animal model of
      neuropathic pain.
AB  - Peripheral nerve injury is associated with local inflammation and neuropathic
      pain. In this study we investigated the local expression of the inducible isoform
      of nitric oxide synthase (iNOS) following a chronic constriction injury (CCI) to
      the sciatic nerve, a rat model of neuropathic pain. Western blot analysis and
      immunohistochemical co-localization methods were used to identify temporal and
      spatial expression of iNOS and its cells of origin. Changes in mRNA were analyzed
      by RT-PCR and iNOS specific primers. We report that CCI injury induced local iNOS
      expression in both macrophages and Schwann cells within and distal to the injury
      site. The local increase in iNOS mRNA expression paralleled both the temporal and
      spatial protein expression. This study supports the hypothesis that CCI is
      associated with a local inflammatory reaction mediated at least in part by iNOS.
      Local activation of the iNOS-NO system may play an important role in the
      pathogenesis of peripheral nerve injury and neuropathic pain.

PMID- 10076905
TI  - Growth inhibition of Staphylococcus aureus by H2O2-producing Lactobacillus
      paracasei subsp. paracasei isolated from the human vagina.
AB  - H2O2 production by certain Lactobacillus strains is one of the mechanisms that
      helps to regulate the vaginal ecosystem. This paper describes the kinetics of
      H2O2 production by two different strains of Lactobacillus paracasei subsp.
      paracasei under different culture conditions and the effect of this metabolite on
      the growth of Staphylococcus aureus. L. paracasei F2 produced 2.72 mmol 1-1 H2O2
      while L. paracasei F28 produced 1.84 mmol l(-1), both in agitated cultures.
      Although L. paracasei F2 produced a higher H2O2 concentration than L. paracasei
      F28, H2O2 production per number of live bacterial cells was 10-fold higher for
      F28. The latter also showed a faster decrease in viability during the stationary
      phase. There were no detectable levels of H2O2 in cultures without agitation.
      H2O2-producing lactobacilli inhibited growth of S. aureus in a plaque assay and
      in mixed cultures, depending on the initial inoculum of the pathogen.

PMID- 10076906
TI  - Immune effector responses to an excretory-secretory product of Giardia lamblia.
AB  - The prior immunisation of mice with purified excretory-secretory product (ESP)
      led to a complete failure of Giardia lamblia colonisation following challenge
      inoculation of these animals with trophozoites. The prior immunisation of mice
      with ESP resulted in a significant stimulation of local immunity as evidenced by
      a significant enhancement of T helper/inducer activity along with a significant
      increase in immunoglobulin A-bearing cells. Further, the presence of anti-ESP
      antibodies in the serum of immunised as well as immunised-challenged animals
      indicated the stimulation of the systemic lymphoid system. This suggests that the
      ESP is highly immunogenic and it could be one of the major antigens of G. lamblia
      responsible for protection against the infection.

PMID- 10076907
TI  - The SCID/Beige mouse as a model to investigate protection against Yersinia
      pestis.
AB  - In this study, we have shown that severe combined immunodeficient/beige mice
      reconstituted with hyperimmune Balb/c lymphocytes can be used as a model to
      demonstrate adoptive and passive protection against plague infection.
      Reconstitution of severe combined immunodeficient/beige mice was successful in
      nine out of ten mice as demonstrated by spleen colonisation and sustained
      circulating immunoglobulin titres. Furthermore, an increase in antibody titre was
      evident after a booster immunisation of reconstituted mice. Presence of
      circulating antibody correlated with protection against a systemic plague
      challenge and indicated that in reconstituted mice adoptive transfer of a
      functional immune system had occurred. The severe combined immunodeficient/beige
      mouse was also used to demonstrate passive protection against inhaled and
      systemic plague infection. The reconstituted severe combined
      immunodeficient/beige mouse model demonstrating protective immunity against
      plague will be further developed to identify the immune cell subsets responsible
      for this protection.

PMID- 10076908
TI  - Infection with respiratory syncytial virus enhances expression of native
      receptors for non-pilate Neisseria meningitidis on HEp-2 cells.
AB  - Respiratory virus infections have been suggested to be predisposing factors for
      meningococcal disease. Respiratory syncytial virus (RSV) affects young children
      in the age range at greatest risk of disease caused by Neisseria meningitidis. It
      has been previously shown that glycoprotein G expressed on the surface of RSV
      infected HEp-2 cells (a human epithelial cell line) contributed to higher levels
      of binding of meningococci compared with uninfected cells. The aim of the present
      study was to examine the effect of RSV infection on expression of surface
      molecules native to HEp-2 cells and their role in bacterial binding. Flow
      cytometry and fluorescence microscopy were used to assess bacterial binding and
      expression of host cell antigens. Some molecules analysed in this study have not
      been reported previously on epithelial cells. RSV infection significantly
      enhanced the expression of CD15 (P < 0.05), CD14 (P < 0.001) and CD18 (P < 0.01),
      and the latter two contributed to increased binding of meningococci to cells but
      not the Gram-positive Streptococcus pneumoniae.

PMID- 10076909
TI  - Aspergillus fumigatus catalases: cloning of an Aspergillus nidulans catalase B
      homologue and evidence for at least three catalases.
AB  - The presence of catalases in the water soluble fractions of three Aspergillus
      fumigatus strains was investigated using non-denaturing and denaturing
      polyacrylamide gel electrophoresis and Western analysis. Using non-denaturing
      polyacrylamide gel electrophoresis and staining for catalase activity, three
      separate catalases were identified. An A. fumigatus catalase gene (catB) was
      cloned from genomic DNA using the Aspergillus niger catR gene as a probe.
      Polyclonal antibodies were raised to a glutathione S-transferase-CatB fusion
      product expressed in Escherichia coli. Western analysis indicated that, under
      denaturing conditions, the polyclonal antibody recognised a 90-kDa band and under
      non-denaturing conditions, two separate bands were identified. These results
      indicate that A. fumigatus in addition to CatB, produces at least two other
      catalases, one of which is similar in size to CatB. The polyclonal antibody was
      also used to observe catalase expression in mice, experimentally infected with A.
      fumigatus. Staining was observed heterogeneously throughout the fungal hyphae.
      This result indicates that catalase is produced by A. fumigatus during invasive
      aspergillosis.

PMID- 10076910
TI  - Possible virulence factors of Staphylococcus aureus in a mouse septic model.
AB  - Twenty clinical isolates of Staphylococcus aureus were examined to elucidate the
      virulence factors which are directly related to lethality in a mouse septic
      model. Heat or formalin treatment of the organism abolished the lethal activity
      of the live organism during challenge intravenously administered via the tail
      vein. Nevertheless, injection of ten times concentrated culture supernatant fluid
      (SUP) showed lethal activity in the mouse. However, there was no lethality when
      SUP was heated at 60 degrees C for 15 min. To examine variations of SUP lethality
      among strains, we collected 20 strains of S. aureus from four different
      hospitals. Then, we compared several factors for SUP lethality, which were the
      extracellular toxins and enzymes, such as toxic shock syndrome toxin 1,
      enterotoxin A, B, D, and hemolysins (alpha,beta,gamma), and also cytotoxic
      activity to human polymorphonuclear leukocytes and Vero cells. No difference was
      found among these factors except cytotoxic activity to Vero cells. Furthermore,
      we compared two strains in a mouse septic model according to the grade of
      bacteremia and lethal events. We found that mortality was higher with challenge
      by the strain whose SUP was lethal in comparison to the strain whose SUP was not
      lethal, even though the viable bacteria counts in the septic blood in both
      strains were not significantly different. This strongly supports the possibility
      that extracellular products, not the cell wall components, of S. aureus play the
      key role in the lethal event in this mouse septic model. In addition, among the
      extracellular products, those which have cytotoxic activity to Vero cells may
      contribute to the lethality in sepsis caused by S. aureus in this murine model.

PMID- 10076911
TI  - New approaches to vaccines against tuberculosis: where we stand and where we want
      to go. Introductory remarks to the symposium.

PMID- 10076912
TI  - Immunity to tuberculosis: a delicate balance between protection and pathology.
AB  - The currently used tuberculosis (TB) vaccine (Bacillus Calmette-Guerin) does not
      consistently prevent pulmonary infection. Novel vaccine strategies require an in
      depth characterization of the cellular and molecular mechanisms of
      antituberculous protection. This review summarizes relevant data obtained in
      animal models of TB infection. In mycobacterial infections, immunologically
      mediated protection is intrinsically associated with tissue damage in the form of
      granuloma formation. The implications of this finding for future vaccine design
      and evaluation are discussed.

PMID- 10076913
TI  - Immunological evaluation of novel Mycobacterium tuberculosis culture filtrate
      proteins.
AB  - Culture filtrate from Mycobacterium tuberculosis contains molecules which can
      promote protective immunity to tuberculosis in animal models. Six novel proteins
      in the region of 17-29 kDa were purified and investigated for their immunological
      relevance in M. tuberculosis-infected mice, guinea pigs and tuberculosis
      patients. The proteins CFP17, CFP21, CFP25 and CFP29 were all identified as
      strong interferon-gamma inducers in M. tuberculosis-infected mice and in
      tuberculosis patients. The CFP21 protein is encoded in the genomic region RD-2
      which is deleted from a number of BCG strains and the diagnostic potential of
      this antigen was evaluated.

PMID- 10076914
TI  - Live antigen carriers as tools for improved anti-tuberculosis vaccines.
AB  - Recombinant (r) Mycobacterium bovis BCG strains have been constructed which
      secrete biologically active listeriolysin (Hly) fusion protein of Listeria
      monocytogenes. In human and murine macrophage-like cell lines, intracellular
      persistence of these r-BCG strains was reduced as compared to the parental BCG
      strain. By immunogold labelling Hly was detected in membrane structures and
      within the phagosomal space of macrophages. Hly fusions consistently co-localized
      with a lysosome-associated membrane glycoprotein (LAMP-1) suggesting that
      membrane attack conformation of Hly was not altered. Although r-BCG
      microorganisms apparently did not egress into the cytoplasmic compartment of host
      cells, they both improved major histocompatibility complex class I presentation
      of co-phagocytosed soluble ovalbumin as compared with wild-type BCG microbes.
      These data suggest that Hly secretion endows BCG with an improved capacity to
      stimulate CD8 T cells. Because CD8 T cells play a major role in protection
      against tuberculosis such Hly-secreting r-BCG constructs are anti-tuberculosis
      vaccine candidates. In addition, we report on our r-Salmonella typhimurium
      expression system combined with the HlyB/HlyD/ TolC export machinery for
      delivering the prominent mycobacterial antigen Ag85B for immune recognition.

PMID- 10076915
TI  - Key features of candesartan cilexetil and a comparison with other angiotensin II
      receptor antagonists.
AB  - Current research on angiotensin II AT1-receptor antagonists (AIIRAs) and selected
      studies presented at the recent symposium held in Amsterdam, The Netherlands, on
      6 June 1998, titled 'Angiotensin II Receptor Antagonists are NOT all the Same'
      are reviewed. AIIRAs offer a number of potential advantages over alternative
      antihypertensive agents acting via the renin-angiotensin-aldosterone system. They
      combine blood pressure-lowering effects at least equivalent to those of
      angiotensin-converting enzyme (ACE) inhibitors, coupled with placebo-like
      tolerability. Candesartan cilexetil is a novel AIIRA that has demonstrated
      clinical efficacy superior to losartan, has a sustained duration of action over
      24 hours (trough:peak ratio close to 100%) and is well tolerated in patients with
      essential hypertension. Candesartan cilexetil has a rapid onset of action
      (approximately 80% of total blood pressure reduction within the first 2 weeks)
      and dose-dependent effects on blood pressure, is comparable in efficacy to a
      number of classes of antihypertensives, and is effective in combination therapy
      (eg, with hydrochlorothiazide and amlodipine). This favourable profile may be due
      in part to the highly selective, tight binding to and slow dissociation of
      candesartan from the AT1 receptor. Preliminary studies suggest that candesartan
      cilexetil also protects end organs (kidney, heart, vasculature, and brain) beyond
      blood pressure control.

PMID- 10076916
TI  - Angiotensin II receptor pharmacology and AT1-receptor blockers.
AB  - Angiotensin II (Ang II) has diverse physiological actions leading, for example,
      to increases in extracellular volume, peripheral vascular resistance and blood
      pressure, and has also been implicated in the regulation of cell growth and
      differentiation. Molecular cloning and pharmacological studies have defined two
      major classes of Ang II receptors, designated as AT1 and AT2. Most effects of Ang
      II are mediated by AT1 receptors. Much less is known about the physiological role
      of AT2 receptors. Recent evidence suggests involvement of AT2 receptors in
      development, cell differentiation, apoptosis and regeneration in various tissues.
      AT1 and AT2 receptors have been shown to exert counteracting effects on cellular
      growth and differentiation, vascular tone and the release of arginine vasopressin
      (AVP). In each condition the AT2 receptor appears to down-modulate actions
      mediated by the AT1 receptor, resulting in decreased cellular proliferation,
      decreased levels of serum AVP levels or decreased vasoconstrictor responses. In
      addition, in neuronal cell lines, the AT2 receptor reportedly exerts
      antiproliferative effects and promotes neurite outgrowth, an effect accompanied
      by significant changes in the gene expression pattern of growth- and
      differentiation-related genes.

PMID- 10076917
TI  - Effect of an angiotensin II receptor antagonist, candesartan cilexetil, on canine
      intima hyperplasia after balloon injury.
AB  - The roles of angiotensin (Ang) II as produced by two different enzymes,
      angiotensin-converting enzyme (ACE) and chymase, were investigated in a canine
      experimental model where intima hyperplasia was induced by balloon
      catheterization in the common carotid and femoral arteries. The animals received
      oral candesartan cilexetil (3 mg/kg) or enalapril (10 mg/kg) twice a day for 5
      weeks. After 1 week of active drug therapy, the common carotid and femoral
      arteries were unilaterally injured by balloon catheterization. In the common
      carotid arteries, both ACE and chymase activities were increased by the injury,
      with the increase in chymase activities being greater than that in ACE
      activities. In the femoral arteries, ACE, but not chymase, activities were
      significantly increased by the injury. Both candesartan cilexetil and enalapril
      reduced blood pressure almost equally. Enalapril increased plasma renin activity
      more strongly than did candesartan cilexetil, and significantly decreased
      vascular and plasma ACE activities. Candesartan cilexetil significantly
      suppressed the formation of intima hyperplasia in both the carotid and femoral
      arteries, while enalapril significantly suppressed intima hyperplasia in the
      femoral, but not in the carotid arteries. These results indicate that local Ang
      II production by ACE and chymase is involved in the hyperplasia seen in injured
      intima, and the difference in the inhibitory action of candesartan and enalapril
      reflects the extent of contribution of each enzyme. The effect of the ACE
      inhibitor, enalapril, depended on the activity of ACE, whereas that of the Ang II
      receptor antagonist, candesartan, was independent of ACE activity.

PMID- 10076918
TI  - Clinical efficacy and tolerability of candesartan cilexetil. Candesartan Study
      Groups in Japan.
AB  - Clinical trials of candesartan cilexetil conducted in Japan are reviewed.
      Candesartan cilexetil inhibited the pressor response to intravenous angiotensin
      II in healthy volunteers, with peak effects observed at 4 or 8 h after oral
      dosing; suppressing effects persisted up to 24 h. In 14 multicentre studies with
      928 hypertensive patients treated for 8 to 12 weeks, candesartan cilexetil had an
      efficacy rate (reduction of systolic/diastolic blood pressure > or = 20/10 mm Hg
      and/or mean blood pressure > or = 13 mm Hg) of 72% and 63%, and an adverse effect
      rate of 9.9% and 7.3%, in patients with mild-to-moderate essential hypertension
      and those with impaired renal function, respectively. When data for elderly
      patients were analysed, there was no difference in efficacy and tolerability
      compared to non-elderly patients. In a double-blind comparative study,
      candesartan cilexetil was superior to enalapril in hypertensive patients:
      efficacy rate, 74% vs 66% (NS); adverse symptom rate, 10.4% vs 27.3% (P < 0.01);
      incidence of cough, 1.5% vs 14.8% (P < 0.01). Treatment with 2-8 mg of
      candesartan cilexetil once daily for 8 to 12 weeks reduced the left ventricular
      mass index without deterioration of cardiac function. In conclusion, 4-12 mg of
      candesartan cilexetil once daily is effective and well tolerated in patients with
      essential hypertension, including elderly patients, those with severe
      hypertension, and hypertensive patients with renal insufficiency. Its improved
      tolerability profile over angiotensin-converting enzyme inhibitors, as well as
      its end-organ protective effects, suggest that candesartan cilexetil is useful as
      a first-line antihypertensive drug.

PMID- 10076919
TI  - Cardiac and vascular remodelling: effect of antihypertensive agents.
AB  - The 1996 World Health Organization (WHO) recommendations for mild hypertension
      stressed the need to evaluate target-organ lesions as treatment criteria. The
      effects of both vascular and heart remodelling on hypertension must to be taken
      into account, as they adversely influence the prognosis of patients with
      hypertension. It was previously demonstrated that at least three classes of
      antihypertensive agents were able to decrease morbidity and mortality in patients
      with hypertension. Meta-analyses have shown that angiotensin-converting enzyme
      inhibitors seem to have a marked effect on regression of left ventricular
      hypertrophy (LVH). However, the relationship between drug-induced LVH regression
      and reduced morbidity and mortality remains to be confirmed. The effect of
      antihypertensive agents on vascular hypertrophy, as assessed by intima-media
      thickness, and their involvement in reducing morbid events, also have to be
      determined at the vascular level. As experimental data have highlighted the
      involvement of angiotensin II in animal models of LVH and vascular hypertrophy
      development, the role of angiotensin II AT1 receptor blockers should also be
      assessed in this indication.

PMID- 10076920
TI  - Role of tissue angiotensin II in myocardial remodelling induced by mechanical
      stress.
AB  - In an in vivo study, spontaneously hypertensive rats (SHR) were treated with an
      angiotensin II (Ang II) type 1 receptor antagonist of candesartan or hydralazine.
      Untreated SHR progressively developed severe hypertension, and treatment with
      candesartan or hydralazine decreased blood pressure. Candesartan reduced left
      ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, the
      relative amount of V3 myosin heavy chain, and interstitial fibrosis, while
      treatment with hydralazine slightly prevented an increase in LV wall thickness,
      but did not exert a significant reduction on other parameters. In an in vitro
      study, neonatal rat cardiomyocytes were cultured on deformable silicone dishes.
      Stretching cardiomyocytes activated second messengers such as protein kinase C,
      Raf-1 kinase, and mitogen-activated protein (MAP) kinase, increasing protein
      synthesis, enhancing endothelin (ET)-1 release, activating the Na+/H+ ion
      exchanger. Moreover, pretreatment with candesartan diminished an increase in
      phenylalanine incorporation, MAP kinase activity, and c-fos gene expression
      induced by the stretching of cardiomyocytes. This suggests that the cardiac renin
      angiotensin system is linked to the formation of pressure-overload hypertrophy
      and that Ang II increases the growth of cardiomyocytes by an autocrine mechanism.
      Finally, we examined the signalling pathways leading to MAP kinase activation
      both in cardiac myocytes and in cardiac fibroblasts. Ang II-evoked signal
      transduction pathways differed between cell types. In cardiac fibroblasts, Ang II
      activated MAP kinase through a pathway including the Gbetagamma subunit of Gi
      protein, Src, Shc, Grb2, and Ras, while Gq and protein kinase C were important in
      cardiac myocytes.

PMID- 10076921
TI  - ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in
      chronic rat models.
AB  - There is now abundant evidence that treatment with angiotensin-converting enzyme
      inhibitors (ACE-I) ameliorates the progression of chronic renal disease.
      Attention has therefore focused on the role of the renin angiotensin-aldosterone
      (RAA) system in mediating the development of progressive glomerulosclerosis and
      angiotensin II (Ang II) has been implicated in several processes thought to be
      important in the pathogenesis of this entity. Conversely, ACE is also known to
      catalyse the breakdown of bradykinin. Thus, ACE-I treatment results in elevated
      bradykinin levels which may cause selective efferent arteriolar dilatation,
      suggesting an alternative explanation for the beneficial effects of this class of
      drugs in chronic renal disease. The development of specific angiotensin type 1
      receptor antagonists (AT1RA) has provided a means of testing the relative
      importance of these two mechanisms. In addition, AT1RAs differ from ACE-I in
      their effect on the RAA system in other aspects which may represent therapeutic
      advantages. This paper reviews studies which have compared ACE-I and AT1RAs in
      several rat models of chronic renal disease. Most have found similar beneficial
      effects including amelioration of proteinuria and glomerulosclerosis, which
      suggests that the effects of ACE-I are due to a reduction in Ang II activity and
      not due to increased levels of bradykinin. One long-term study has suggested
      greater renal protection with candesartan than with enalapril. However,
      conclusions as regards the relative efficacy of these two groups of agents in
      ameliorating the progression of chronic renal disease await the results of
      further long-term studies.

PMID- 10076922
TI  - Effects of candesartan on the proteinuria of chronic glomerulonephritis.
AB  - Angiotensin I-converting enzyme (ACE) inhibitors are commonly used for the
      treatment of hypertension, progressive chronic renal disease, diabetic
      nephropathy, and congestive heart failure. Because angiotensin II acts through
      membrane bound type 1 (AT1) and type 2 (AT2) receptors, ACE inhibitors and
      angiotensin II-receptor antagonists have distinct effects. ACE inhibitors inhibit
      production of angiotensin II thus suppressing the action of angiotensin II on
      both AT1 and AT2. In contrast, the effect of AT1-receptor antagonists is to
      selectively block the activation of the AT1 receptor. This AT1-receptor blockade
      leaves the AT2 receptors unopposed to elevated levels of endogenous angiotensin
      II. Thus, there may be an advantage of AT1-receptor blockade over ACE inhibition
      in the management of a variety of chronic vascular diseases, including chronic
      glomerulonephritis and other glomerular diseases. In a clinical trial
      candesartan, an AT1-receptor antagonist, effectively lowered urinary protein
      excretion in patients with chronic glomerular nephritis. Evidence indicates that
      functionally active AT1 receptors, as well as AT2 receptors, are present in both
      afferent and efferent arteriole of the glomerulus, and that angiotensin II
      induces afferent and efferent arteriolar dilatation via AT2 receptors.

PMID- 10076923
TI  - Effects of candesartan cilexetil on oxidative state and renal function in 5/6
      nephrectomized rats.
AB  - We have investigated the influence of a novel angiotensin II type 1 receptor
      antagonist, candesartan cilexetil, on the oxidative state of renal tissue and
      renal function in 5/6 nephrectomized rats, and compared its effects with those of
      an angiotensin-converting enzyme inhibitor, enalapril. Candesartan cilexetil (1
      and 5 mg/kg per day), enalapril (5 mg/kg per day) and vehicle were orally
      administered once daily for 16 weeks after 5/6 nephrectomy. There was a marked
      degree of proteinuria evident prior to treatment, an average of 5.69 mg/mg
      creatinine in the nephrectomized rats, vs 1 to 2 mg/mg creatinine in the control
      group matched for species and body weight. Inhibition of development of
      proteinuria by candesartan cilexetil was dose dependent. Enalapril also
      significantly blunted the rise in urinary protein. Malondi-aldehyde content in
      the homogenate from the renal cortex increased significantly in the
      nephrectomized rats compared to control animals. This elevation of malondi
      aldehyde content was unaffected by administration of either candesartan cilexetil
      or enalapril. Antioxidative enzyme (glutathione peroxidase, superoxide dismutase,
      and catalase) activities in the renal tissue were not affected by any active
      treatment. Elevation of lipid peroxide in remnant renal tissue suggests that
      oxidative stress may contribute to the progression of renal injury in the
      nephrectomized rats. Neither candesartan cilexetil nor enalapril affected
      antioxidant defenses in renal tissue in nephrectomized rats, indicating that
      mechanisms other than alteration in oxidative stress are involved in the
      renoprotective effects of candesartan cilexetil and enalapril.

PMID- 10076924
TI  - Effect of an angiotensin II receptor antagonist, candesartan, on insulin
      resistance and pressor mechanisms in essential hypertension.
AB  - Candesartan (8 mg/d) was administered for 2 weeks to eight patients with
      essential hypertension to investigate the effect of an angiotensin II receptor
      antagonist on insulin sensitivity. The effect of candesartan on sodium-retaining
      action and the activation of pressor systems by hyperinsulinaemia, which might be
      related to pressor mechanisms in essential hypertension, was also investigated in
      this study. In patients with essential hypertension, candesartan restored insulin
      sensitivity to the level of that in normotensive subjects. Candesartan treatment
      attenuated the sodium-retaining action of hyperinsulinaemia. These findings
      suggest that inhibition of angiotensin II action by candesartan can improve
      insulin sensitivity and inhibit the sodium-retaining action associated with
      hyperinsulinaemia in essential hypertension.

PMID- 10076925
TI  - Pharmacologic properties of candesartan cilexetil--possible mechanisms of long
      acting antihypertensive action.
AB  - Candesartan cilexetil has shown potent and long-lasting antihypertensive effects
      in clinical trials and in several animal models of hypertension. In spontaneously
      hypertensive rats, the duration of the antihypertensive effect of candesartan
      cilexetil was compared to those of losartan, valsartan, eprosartan, and
      irbesartan at the same degree of maximal blood pressure reduction. A single oral
      dose of candesartan cilexetil at 0.3 mg/kg reduced maximal blood pressure by
      about 25 mm Hg, and the antihypertensive effect of candesartan cilexetil lasted
      the longest, continuing for more than 1 week, without an effect on circadian
      rhythm. In a rabbit aortic preparation, candesartan, active form of candesartan
      cilexetil, decreased the maximal contractile response of angiotensin II. This
      inhibitory mode was different from that of other angiotensin II-receptor
      antagonists, and showed a shift to the right in the angiotensin II-induced
      contraction curve and/or a small depression of the maximal response. In kinetic
      studies using bovine adrenal cortical membrane and tritiated candesartan, both
      receptor association and dissociation were found to be slow. The dissociation
      rate of tritiated candesartan binding (t1/2 = 66 min) was five times slower than
      that of radiolabelled angiotensin II binding (t1/2 = 12 min). The insurmountable
      inhibition of candesartan in vascular contraction is the result of its tight
      binding and slow dissociation from angiotensin II AT1 receptors. These
      characteristics are related to the potency and long duration of action in
      candesartan cilexetil.

PMID- 10076926
TI  - Location of reticular premotor areas of a motor center innervating craniocervical
      muscles in the mallard (Anas platyrhynchos L.).
AB  - The supraspinal nucleus (SSp) in the mallard, which lies in the rostral spinal
      cord and caudal brainstem, is a motor nucleus that forms the rostral continuation
      of the ventral horn. It contains part of the motoneurons innervating the
      craniocervical muscles. Injections with horseradish peroxidase (HRP) and wheat
      germ agglutinin conjugated to HRP (WGA) in the SSp were used to localize the
      craniocervical premotor neurons in the medullary reticular formation. A mixture
      of WGA and HRP (WGA/HRP) or biotinylated dextran amine (BDA) were injected in the
      different reticular areas to test the results. Small numbers of craniocervical
      premotor neurons were found bilaterally in the ventromedial part of the
      parvocellular reticular formation (RPcvm) and in the caudal extension of RPcvm,
      the nucleus centralis dorsalis of the medulla oblongata, and the gigantocellular
      reticular formation (RGc). In a second series of experiments, WGA/HRP and BDA
      injections in these reticular areas were used to visualize afferent fibers and
      terminals in the SSp. The combination of the two types of experiments shows that
      RPcvm and RGc contain modest numbers of craniocervical premotor neurons. Because
      the reticular formation also contains jaw and tongue premotor neurons and
      receives a variety of sensory projections, the present results suggest that the
      medullary reticular formation plays a role in the coordination of complex
      movements (e.g., feeding). The pattern of afferent and efferent connections of
      the reticular formation is used to redefine its subdivisions in the
      myelencephalon of the mallard.

PMID- 10076927
TI  - Immunohistochemical localization of GABA(B) receptors in the rat central nervous
      system.
AB  - The recent cloning of two gamma-aminobutyric acid(B) (GABA(B)) receptor isoforms
      (GABA(B)R1a/b), which are probably splice variants of the same gene transcript,
      allowed us to develop an antiserum that recognized the receptors in fixed tissue
      and to map their distribution in the rat central nervous system (CNS). We also
      investigated whether GABA(B)R1 colocalizes with glutamic acid decarboxylase
      (GAD), a marker of GABAergic cell bodies and terminals. Although GABA(B)R1-like
      immunoreactivity (GABA(B)R1-LI) was distributed throughout the CNS, several
      distinct distribution patterns emerged: (1) all monoaminergic brainstem cell
      groups appeared to contain very high levels of GABA(B)R1, (2) a very high
      intensity of GABA(B)R1-LI was observed in the majority of the cholinergic regions
      in the CNS, with exception of motoneurons of the third through sixth cranial
      nerve nuclei, and (3) a low density of the receptor was observed in most of the
      nuclei that contain cell bodies of GABAergic projection neurons. The highest
      GABA(B)R1 labeling was observed in the thalamus, interpeduncular nucleus and
      medial habenula. Cell bodies were labeled throughout the neuroaxis. We also
      observed dense neuropil labeling in many regions, suggesting that this receptor
      is localized in dendrites and/or axon terminals. However, in immunofluorescent
      double-labeling experiments for GABA(B)R1 and GAD, we never observed GABA(B)R1-LI
      in GAD-positive axon terminals; this result suggests that the GABA(B)R1 may not
      function as an autoreceptor. Double labeling was observed in the cell bodies of
      Purkinje neurons and in some interneurons. In general, the immunohistochemical
      localization of the GABA(B)R1 correlates well with physiologic and
      autoradiographic data on the distribution of GABA(B) receptors, but some critical
      differences were noted. Thus, it is likely that additional GABA(B) receptor
      subtypes remain to be identified.

PMID- 10076928
TI  - Site-specific immune regulation in the brain: differential modulation of major
      histocompatibility complex (MHC) proteins in brainstem vs. hippocampus.
AB  - Although neurotransmitters and neuropeptides are known to affect immune function
      in vitro and in non-neural tissues, little is known about how the local mix of
      neurochemicals affects immune function in the brain. Here, we study local
      modulation of the class II major histocompatibility complex (MHC) proteins, which
      present antigen to T cells in a key pathway for cell-mediated immune activity.
      Two sites that are well-separated anatomically and have very different
      neuroregulatory environments, the brainstem and hippocampus, were compared. The
      class II-upregulating cytokine, gamma interferon (IFN-gamma, 0.1 to 10,000
      U/site), was injected stereotaxically into the hippocampus and contralateral
      brainstem of adult Charles-derived Fischer rats. Four days later, monoclonal
      antibody staining was used to detect class II MHC proteins on cryostat sections,
      followed by computer-assisted image analysis. As compared to hippocampus, the
      brainstem showed enhanced class II expression at lower IFN-gamma doses, and
      reached a higher plateau. Site-specific class II modulation was also seen within
      the layers of the hippocampus, and among other brain sites. Injection of marker
      protein to visualize the spread of injected protein, plus injection of IFN-gamma
      into alternative sites, suggested that preferential flow cannot explain all of
      the site-specific effects. We suggest that the local neuroregulatory environment
      and/or intrinsic differences among target microglia are likely to play a role.
      Implications for the distribution of pathological changes, such as multiple
      sclerosis plaques, and for local immunotherapy are discussed.

PMID- 10076929
TI  - Glutamate receptor 5/6/7-like and glutamate transporter-1-like immunoreactivity
      in the leech central nervous system.
AB  - Previous physiological and pharmacological evidence has suggested a
      neurotransmitter role for the excitatory amino acid glutamate in the leech
      central nervous system (CNS). In the present study, we sought to localize
      glutamate receptor (GluR) subunits (GluR 5/6/7, GluR 2/3 and N-methyl-D-aspartate
      receptor 1 [NMDAR 1]) and a glutamate transporter subtype [GLT-1] within the
      leech CNS using mono- and polyclonal antibodies. In whole-mounted tissue, small
      cells of the outer capsule and putative microglia labeled with both GluR 5/6/7
      and GluR 2/3 but not NMDAR 1 subunit antisera. In general, GluR 5/6/7-like
      immunofluorescence was both more intense and more widespread than GluR 2/3-like
      immunolabeling. Cryostat-sectioned tissue revealed extensive GluR 5/6/7-like
      immunoreactivity throughout the neuropil as well as labeling within a few
      neuronal somata. GLT-1-like immunoreactivity localized to the inner capsule,
      which is the interface between neuronal somata and the neuropil and is deeply
      invested by processes of neuropil glia. These results complement previous
      physiological and pharmacological findings indicating that the leech CNS
      possesses the cellular machinery to respond to glutamate and to transport
      glutamate from extracellular spaces. Together, they provide further evidence for
      glutamate's role as a neurotransmitter within the leech CNS.

PMID- 10076930
TI  - Quantitative analysis of the dendritic architectures of cat hypoglossal
      motoneurons stained intracellularly with horseradish peroxidase.
AB  - Little is known about the dendritic architecture of cat hypoglossal motoneurons.
      Thus, the present study was done to provide quantitative descriptions of
      hypoglossal motoneurons and to determine correlations between dendritic size
      parameters by using the intracellular horseradish peroxidase (HRP) injection
      technique in the cat. Twelve hypoglossal motoneurons stained with HRP were
      antidromically activated by stimulation applied to the medial branch of
      hypoglossal nerve. Eight (type I) and four (type II) of the 12 motoneurons were
      located in the ventral and dorsal parts of the ventromedial subnucleus of
      hypoglossal nucleus, respectively. The somatodendritic morphology of the two
      types of neurons was remarkably different, especially in the dendritic
      arborization pattern. The type I neurons established an egg-shaped dendritic tree
      that was distributed through the nucleus to the reticular formation; the type II
      dendritic tree was confined within the nucleus and presented a rostrocaudally
      oriented, mirror-image, fan-shape appearance. The total dendritic area and length
      and the number of terminations and branch points were significantly larger for
      type I than for type II neurons. For the two types of neuron, there was a
      positive correlation between stem dendritic diameter and several dendritic size
      parameters. Although the slopes of the regression lines were slightly different
      between the two, these were not statistically significant. The present study
      provides evidence that hypoglossal motoneurons located in the ventromedial
      subnucleus could be divided into two types according to the dendritic
      arborization pattern and quantitative analysis of the dendritic tree and
      according to neuronal location and suggests that the two types of hypoglossal
      motoneurons can be viewed as intrinsically distinct cell types: type I and type
      II, which innervate extrinsic and intrinsic muscles, respectively. In addition,
      the morphometric analysis made it possible to estimate the size of the dendritic
      tree by measuring the stem dendritic diameter.

PMID- 10076931
TI  - Projections of neurons in the periaqueductal gray to pontine and medullary
      catecholamine cell groups involved in the modulation of nociception.
AB  - Stimulation of neurons in the periaqueductal gray (PAG) produces antinociception
      that is mediated in part by noradrenergic neurons that innervate the spinal cord
      dorsal horn. Because norepinephrine-containing neurons are not found in the PAG,
      noncatecholamine neurons in the PAG must project to, and activate, spinally
      projecting catecholamine neurons located in the pons or medulla. The present
      studies determined the projections of neurons in the ventrolateral PAG to the A5,
      A6 (locus coeruleus), and A7 catecholamine cell groups that are known to contain
      spinally projecting noradrenergic neurons. The anterograde tracer biotinylated
      dextran amine (BDA) was injected into the ventrolateral PAG, and labeled axon
      terminal profiles were identified near noradrenergic neurons that were visualized
      by processing tissue sections for tyrosine hydroxylase immunoreactivity. Highly
      varicose, anterogradely labeled terminal profiles were found apposed to the
      dendrites and somata of tyrosine-hydroxylase-immunoreactive neurons and non
      tyrosine-hydroxylase-immunoreactive neurons in the dorsolateral and ventrolateral
      pontine tegmentum. These axon terminal profiles were more dense on the side
      ipsilateral to the BDA deposit, and both A7 and locus coeruleus neurons received
      a more dense innervation than did the A5 neurons. Although definitive evidence
      for a direct pathway from PAG neurons to spinally projecting A7 neurons requires
      ultrastructural studies, the results of the present studies provide presumptive
      evidence for direct projections from neurons in the PAG to noradrenergic A7
      neurons that innervate the spinal cord dorsal horn and modulate pain perception.
      If neurons in the ventrolateral PAG do form synapses with noradrenergic A7
      neurons, these spinally projecting catecholamine neurons may mediate part of the
      analgesic effect produced by systemic administration of morphine. In contrast,
      the projections of PAG neurons to the A5 cell group and the locus coeruleus may
      mediate the cardiovascular and motor effects produced by stimulation of sites in
      the ventrolateral PAG.

PMID- 10076932
TI  - Immune stress activates putative nitric oxide-producing neurons in rat brain:
      cumulative effects with restraint.
AB  - Immune and restraint stresses induce changes in the hypothalamo-pituitary-adrenal
      axis activity and autonomic function. In the hypothalamus, the paraventricular
      nucleus (PVN) plays an integral role, and nitric oxide (NO) is hypothesized to
      participate in this process. We used 1) intravenous injections of
      lipopolysaccharide (LPS, 125 microg/kg) to identify activated (Fos-positive)
      putative NO-producing neurons, 2) retrograde tracing to determine if autonomic
      medullary regions signal the PVN to mediate this activation, and 3) intravenous
      LPS injections plus restraint stress to determine if responses to restraint are
      altered by the presence of immune stress. At 2 hours after LPS injections,
      approximately 15% of putative NO-producing neurons were activated in the nucleus
      of the tractus solitarius (NTS) and ventrolateral medulla (VLM); about half of
      the putative NO neurons in the PVN were activated. In LPS + restraint rats, the
      percentage of activated putative NO neurons in the PVN was not significantly
      different from LPS-treated rats, but the numbers of putative NO neurons and
      activated NO neurons per section increased significantly. Retrogradely labeled
      neurons were found mostly in the middle NTS and VLM, and about 75% were
      activated. No neurons in the NTS or VLM were triple labeled. The results show
      that putative NO-producing neurons in the PVN, NTS, and VLM are activated by
      circulating LPS. However, the LPS-induced signaling to the PVN likely occurs
      through pathways other than the NO network of neurons in NTS or VLM. Finally,
      superimposition of restraint stress onto animals already exposed to immune stress
      stimulates the NO system in the PVN to a greater extent than either stress alone.

PMID- 10076933
TI  - Close spatial-temporal relationship between islet-1-expressing cells and growing
      primary afferent axons in the dorsal spinal cord of chick embryo.
AB  - The relationship between the appearance of Islet-1-expressing cells and the
      longitudinal growth of primary afferent axons (PAAs) in the dorsal spinal cord of
      chick embryos was examined. Islet-1-expressing cells first appeared in the dorsal
      spinal cord at embryonic days (E) 3-3.5. These immunoreactive cells were aligned
      in a longitudinal column in close proximity to longitudinally elongating PAAs in
      the presumptive dorsal funiculus. By E8, when many PAAs invade the spinal gray
      matter, Islet-1-expressing cells had disappeared in the dorsal spinal cord.
      Following the dorsoventral rotation of the spinal cord in ovo before the invasion
      of PAAs, a close topographical relationship between Islet-1-expressing cells and
      PAAs was maintained. These results suggest that Islet-1-expressing cells may play
      a role in the longitudinal growth of PAAs in the dorsal funiculus.

PMID- 10076934
TI  - Retinal mitosis is regulated by dopa, a melanin precursor that may influence the
      time at which cells exit the cell cycle: analysis of patterns of cell production
      in pigmented and albino retinae.
AB  - A melanin-associated agent seems to play a role in regulating retinal
      development. When absent, diverse deficits occur. There is evidence that this
      agent regulates patterns of mitosis. This study examines retinal development in
      pigmented and albino rats to identify the regulating agent and its mode of
      action. Throughout neurogenesis, many more mitotic profiles are found in albinos
      than pigmented animals. At the peak of retinal neurogenesis, approximately 50%
      more mitotic profiles are found in albinos than in matched pigmented animals,
      resulting in abnormal retinal thickening. Concurrently, increasing numbers of
      pyknotic nuclei are identified, such that later in development retinal thickness
      normalises. However, the crude centre-to-periphery pattern of cell production is
      preserved. Abnormal cell proliferation is found in a range of albino rat strains,
      but it is not present in their brains, confirming that the abnormality is ocular
      and melanin related. Dopa is a critical element in initial stages of melanin
      synthesis and is present in abnormally low levels in developing albino retinae.
      Furthermore, it is an antimitotic agent. Addition of dopa to albino eyes in vitro
      normalises patterns of cell production. These results are consistent with the
      hypothesis that dopa is a major regulator of retinal cell production and that it
      influences the capacity of cells to exit the cell cycle.

PMID- 10076935
TI  - Epithelial Na+ channel subunits in rat taste cells: localization and regulation
      by aldosterone.
AB  - Amiloride-sensitive Na+ channels play an important role in transducing Na+ salt
      taste. Previous studies revealed that in rodent taste cells, the channel shares
      electrophysiological and pharmacological properties with the epithelial Na+
      channel, ENaC. Using subunit-specific antibodies directed against alpha, beta,
      and gamma subunits of rat ENaC (rENaC), we observed cytoplasmic immunoreactivity
      for all three subunits in nearly all taste cells of fungiform papillae, and in
      about half of the taste cells in foliate and vallate papillae. The intensity of
      labeling in cells of vallate papillae was significantly lower than that of
      fungiform papillae, especially for beta and gamma subunits. Dual localization
      experiments showed that immunoreactivity for the taste cell-specific G protein,
      gustducin, occurs in a subset ofrENaC positive taste cells. Aldosterone is known
      to increase the amiloride sensitivity of the NaCl taste response. In our study,
      increases in blood aldosterone levels enhanced the intensity of apical
      immunoreactivity for beta and gamma rENaC in taste cells of all papillae. In
      addition, whole cell recordings from isolated taste cells showed that in
      fungiform papillae, aldosterone increased the number of amiloride-sensitive taste
      cells and enhanced the current amplitude. In vallate taste cells, which are
      normally unresponsive to amiloride, aldosterone treatment induced an amiloride
      sensitive current in about half of the cells. Immunoreactivity for rENaC subunits
      also was present in nonsensory epithelial cells, especially in the anterior
      portion of the tongue. In addition, immunoreactivity for all subunits, but
      especially beta and gamma, was associated with some nerve fibers innervating
      taste papillae. These extragustatory sites of rENaC expression may indicate a
      role for this channel in paracellular transduction of sodium ions.

PMID- 10076936
TI  - Prospective randomized comparison of gliding nail and gamma nail in the therapy
      of trochanteric fractures.
AB  - In a prospective randomized study, we compared the new intramedullary implant of
      the gliding nail to the gamma nail in the fixation of 80 unstable trochanteric
      fractures in elderly patients. The preconditions of both groups were comparable.
      We found no differences concerning the operation time, blood loss, period of
      stationary treatment or social situation. Also, the anatomic reconstruction and
      the long-term function according to the Merle d'Aubigne score were comparable.
      Regarding postoperative complications, the gliding nail showed a minor tendency
      of cutting out; this we attribute to the special design of the dynamic blade and
      regard it as the most favourable advantage of this new implant.

PMID- 10076937
TI  - On the timing of soft-tissue reconstruction for open fractures of the lower leg.
AB  - The timing of soft-tissue reconstruction for severe open fractures of the lower
      leg is considered crucial to the later outcome, and yet pertinent publications
      are few. The purpose of this study was to add some based on evidence arguments
      for the choice of the most adequate timing in the management of these injuries.
      Twenty-nine consecutive open fractures of the tibia, including 24 grade 3B and 5
      grade 3C fractures, were treated using a protocol of immediate debridement, early
      definitive skeletal stabilisation and early soft-tissue reconstruction. Fifteen
      lower legs were reconstructed after a mean delay of 4.4 days (range 1-9 days),
      while 14 lower legs were reconstructed immediately, i.e. as an emergency
      procedure on the day of admission. Both groups were comparable for sex, age, type
      of trauma, associated general injuries, type of fracture, associated arterial
      lesion, associated tendon rupture, type of soft-tissue reconstruction and
      duration of follow-up. All patients were reviewed at a mean follow-up of 47
      months (range 15-89 months). In the delayed reconstruction group the time to
      full, unprotected weight-bearing (P = 0.0021), the time to definitive union (P =
      0.0049), the number of reoperations (P = 0.0001) and the infection rate (P =
      0.0374) were significantly higher. The data suggest that immediate reconstruction
      is, the general condition of the patient permitting, the timing of choice for
      soft-tissue coverage.

PMID- 10076938
TI  - Simulator trials to determine the wear of the combination aluminium oxide ceramic
      carbon fibre reinforced plastic (CFRP) used as an insert in a hip socket.
AB  - Hip simulator trials were conducted to determine the initial wear between alumina
      femoral heads and carbon fibre reinforced plastic (CFRP, CAPROMAN) insert in a
      titanium socket. A force of 2500 N and a frequency of 0.857 H were applied. Using
      surface and sphericity measurement techniques, the amount of wear was determined.
      After 500,000 cycles, the centre of the head had moved by 10 microm into the
      insert, and the average radius increased by 2 microm. After 1 million cycles, the
      additional changes were less than 1 microm. Based on an examination of retrieved
      implants (wear rate: 6.1 microm/year) and based on the simulator results, the
      combination alumina-CFRP inserts could be approved for total hip replacement.

PMID- 10076939
TI  - Effects of glucocorticoids on bone mineral density in rheumatoid arthritis
      patients. A longitudinal study.
AB  - We carried out a comparative study in 78 post-menopausal women with rheumatoid
      arthritis (RA). Forty-four women with a mean disease duration of 17.5 years had
      been treated with low-dose glucocorticoid (prednisone at < 5 mg/day) for at least
      12 months. They were studied for an average period of 3 years and 8 months. The
      remaining 34 women had been treated only with nonsteroidal anti-rheumatic drugs
      (NSAIDs) and served as the control group. Bone mineral density (BMD) in the
      lumbar spine (L2-4) and femoral neck was measured by dual-energy X-ray
      absorptiometry (DXA). Reduction of BMD in the lumbar spine was significant in
      both groups (P < 0.05 to approximately 0.01), but there was no statistically
      significant difference between the two groups. BMD of the femoral neck decreased
      significantly (P < 0.05) in the prednisone group, but again the difference was
      not significant between the two groups. Our data suggest that low-dose prednisone
      administration probably does not induce significant axial bone loss in female RA
      patients.

PMID- 10076940
TI  - Bone tumors in the pelvis presenting growth during pregnancy.
AB  - Among 56 cases of a giant cell tumor of bone (GCT) and 52 cases of chondrosarcoma
      (CSA) in our series, four patients were discovered to have a tumor in the pelvic
      bone that grew in size during pregnancy. These four rare cases are described
      here. They include three cases of a GCT in the sacrum and one case of a CSA in
      the innominate bone. The dextran-coated charcoal assay and immunohistochemical
      techniques demonstrated the independence of these tumors from hormonal regulation
      despite the growth stimulated during pregnancy. It was concluded that the delay
      in detection of these tumors in the pelvis was just related to the opportunity
      afforded for unexpected growth during pregnancy. Surgical management was
      difficult due to the delay in tumor detection. The initial complaints such as
      pain, discomfort, or numbness around the pelvis were misinterpreted as symptoms
      of pregnancy. It should be kept in mind that during pregnancy, any pain or
      numbness in the pelvic region could be the direct result of a tumor in the pelvic
      bone.

PMID- 10076941
TI  - Wear of alumina ceramics prosthesis.
AB  - To investigate the process of wear in the total knee prosthesis consisting of
      alumina ceramics (Al-ceramics) and ultra-high molecular weight polyethylene
      (UHMWP) in vivo, we observed the fine structures of the articular surface of the
      prostheses used for four patients with osteosarcoma of the distal femur. We also
      examined the wear debris in the surrounding soft tissues. The prostheses were
      extracted at autopsy between 13 and 48 months after surgery. An increase of
      pores, indicating where Al-ceramics grains fell off, and many streaks on the
      UHMWP running parallel to the gliding direction of the joint were observed on the
      articular surface. The streaks had similar widths to the Al-ceramics grains. Al
      ceramics debris was detected in the soft tissues around the joint mixed with
      UHMWP debris. We concluded that the wear of UHMWP in Al-ceramics prosthesis was
      promoted by interposition of Al-ceramics debris.

PMID- 10076942
TI  - Four-part posterior fracture--dislocations of the shoulder. Treatment by limited
      open reduction and percutaneous stabilization.
AB  - Ten patients who had been treated by limited open reduction and percutaneous
      stabilization for four-part posterior fracture-dislocation of the shoulder were
      followed-up for an average of 3.2 years postoperatively. According to the
      criteria of Neer, the result was excellent in nine patients, with an average
      Constant score of 95.7. There was one failure who showed complete avascular
      necrosis. All patients with excellent results had at least 1 mm of the neck
      portion of the head fragment intact.

PMID- 10076943
TI  - Effects of essential amino acids and lactose on bony fractures and defects in
      rabbits: a preliminary histomorphometric study.
AB  - An experimental study was performed in order to test the possibility of improving
      bone repair with the administration of a drug (Calciofix, Farmaceutici Damor SpA,
      Naples, Italy) containing essential amino acids and lactose. Fifty rabbits were
      submitted to an open transversal fracture of the left fibula and to a right
      femoral condyle defect. They were left untreated or treated daily with the drug
      orally and were divided into subgroups depending on the experimental time: 15,
      30, 40, 50, 60 days. Histomorphometric data showed a significantly faster healing
      rate in treated animals compared with untreated ones. Firstly, on day 30 there
      was a significantly larger amount of cartilage in the control bone callus (P <
      0.01). On day 50 a significant difference existed between trabecular and lacunar
      percentages in the two subgroups (P < 0.0005). At 60 days no significant
      differences were observed, but bony trabeculae had become more oriented parallel
      to the long axis of the bone in treated animals. Secondly, after 15 days the
      defect area was significantly smaller in treated animals than in the untreated
      ones (P < 0.01). At 30 and 40 days, respectively, significant differences existed
      between the two subgroups in connective tissue and mature bone percentages (P <
      0.01 and P < 0.001). Our results seem to demonstrate that the drug significantly
      accelerates the rate of bone formation in fractures and bone defects in rabbits.

PMID- 10076944
TI  - Patellar motion analyzed by kinematic and dynamic axial magnetic resonance
      imaging in patients with anterior knee pain syndrome.
AB  - Ten consecutive patients (12 knees), all women, with anterior knee pain syndrome
      participated in the study. The patellofemoral joints were examined with the knee
      in 0 degrees, 10 degrees, 20 degrees, and 30 degrees of flexion. At each knee
      position, kinematic and dynamic, an axial magnetic resonance (MR) image was used
      to focus on the sagittal plane, followed by an axial image focused through the
      middle of the patella. Ten healthy volunteers (20 knees) with no history of
      previous or current knee problems or anterior knee pain also underwent MRI
      scanning following the same procedure. Three angles were measured: patellar tilt
      angle (PTA), sulcus angle (SA), and congruence angle (CA). For statistical
      analyses, we used the Mann-Whitney U-test. Compared with the control knees, five
      patterns of malalignment were identified. The most frequently observed was tilt
      and lateralisation, with elevated CA and decreased PTA. In extension, the average
      CA for this group was 22 degrees and PTA -4.8 degrees vs -8.1 degrees and 14.3
      degrees for control knees respectively. Contraction of the muscles caused tilt of
      the patella in symptomatic knees. This decrease of the PTA was statistically
      significant in extension (P < 0.05) and in 10 degrees of flexion (P < 0.05).
      Contraction of the thigh muscle increased CA in 30 degrees of flexion. This
      lateral pull was statistically significant (P < 0.05). There were no
      statistically significant differences of SA between the groups, regardless of
      muscle contraction or flexion angle. At 30 degrees of flexion, muscle contraction
      increased CA and decreased PTA. In our opinion, imaging in the first 30 degrees
      of flexion with thigh muscle contraction is necessary for a correct diagnosis.

PMID- 10076945
TI  - Errors of computer-assisted migration analysis in conventional radiographs of
      femoral hip implants--an experimental study.
AB  - Several methods have been described in the literature in order to analyze
      migration of femoral hip implants in conventional radiographs. However, no
      measurements were done regarding the potential errors inherent in such
      unstandardized radiographs of daily routine. In order to quantify this lack of
      reproducibility, we carried out experimental examinations with radiographs of a
      hip revision prosthesis, where different variables of technical X-ray conditions
      and femoral positions were changed. All radiographs were analyzed with a computer
      assisted processing system by different procedures. At first, the radiographs
      were calibrated geometrically. Then, particular reference distances between
      defined points of the implant and cortical bone structures were analyzed
      quantitatively. The error of the axial migration analysis was up to 11.11 mm
      concerning different femoral positions, up to 8.29 mm in the case of different
      source-to-film distances and up to 2.21 mm due to different lateral localizations
      of the central X-ray focus. Significant errors for the migration analysis in the
      transverse and rotational planes were only found under conditions of varying the
      femoral position, and not under different technical X-ray conditions. From these
      experimental results, we derived the following criteria to minimize failure in a
      quantitative radiographic migration analysis: (1) the patient's leg has to be
      placed into an antirotation device to ensure identical object position; (2) the
      same source-to-film distance has to be used; (3) the central X-ray focus has to
      be localized on the center of the film-cassette; (4) film-screen systems should
      be of the same type and size; (5) the object has to be placed in the same
      position as in previous radiographs. As a conclusion, only if these
      standardization criteria are respected in the daily routine of conventional
      radiographs will an effective and meaningful use of migration analysis systems be
      possible to prove or to exclude mechanical failure of femoral hip implants in
      prospective longitudinal follow-up series.

PMID- 10076946
TI  - Revascularization and new bone formation in heat-treated bone grafts.
AB  - Human imnmunodeficiency virus (HIV) infection is one of the possible serious
      complications associated with bone allografts. In order to prevent infection,
      grafted bone is sterilized by various treatments. Heat treatment has attracted
      attention as a simple and practical method. We carried out a histological study
      of the influence of heat treatment on autogenic bone grafts. To eliminate the
      problem of antigenicity of grafted bone, we used autografts, not allografts.
      Three types of heat-treated autografts were employed: heat-treated at 60 degrees
      C for 30 min, at 80 degrees C for 10 min, and at 100 degrees C for 5 min; as a
      control, fresh autografts were replaced in the rabbits' ilium. One, 2, 4 and 8
      weeks after grafting, we performed microangiography and prepared two types of
      samples: transparent and haematoxylin-eosin (H&E) stained. Then, using an image
      analyzer, we quantitatively measured revascularization and new bone formation in
      the grafted bone. The grafts heat-treated at 60 degrees C showed early and good
      revascularization and new bone formation, from 1 to 8 weeks. The grafts heat
      treated at 80 degrees C showed relatively good revascularization and new bone
      formation. However, the grafts heat-treated at 100 degrees C showed
      unsatisfactory revascularization and bone formation, less than 40% of control 8
      weeks after grafting. Therefore, heat treatment at 60-80 degrees C does not
      seriously affect revascularization and new bone formation.

PMID- 10076947
TI  - Shock-wave therapy for tennis and golfer's elbow--1 year follow-up.
AB  - Thirty patients with chronic medial epicondylitis were treated with low-energy
      shock waves. They received 500 impulses of 0.08 mJ/mm2 three times at weekly
      intervals. At 1 year follow-up examinations were performed. According to the
      Verhaar criteria, only seven patients reached excellent or good results. In eight
      cases a fair outcome was recorded, and in 14 patients the outcome was poor. Only
      six patients were satisfied with the treatment. The average relief of pain was
      32%. These data were significantly worse than for identically treated patients
      with chronic tennis elbow. Thus, the question arises as to whether extracorporal
      shock-wave therapy is indicated in medial epicondylitis.

PMID- 10076948
TI  - A comparative study of two cerclage systems.
AB  - Intraoperative femoral fracture is a well recognized technical complication of
      cementless total hip arthroplasty (THA). The aim of this study was to establish
      an in vitro model for initiation of fractures of the femur in cementless THA and
      to assess the effect of fracture fixation by cerclage wiring. An in vitro
      comparison of two methods of cerclage fixation was performed using steel wire
      (Protasul) versus multifilament Vitallium alloy cable. Ten fresh human femur
      specimens were studied. Longitudinal fractures were created on a material testing
      machine. The force to create a longitudinal fracture in the femur was 1915 N to
      9288 N (median 6531 N). This force corresponds 3 to 15 times (median 11 times)
      the body weight. The femoral cortex was fractured in 5 cases ventrally, in 6
      cases medially and in 1 case laterally. After monofile cerclage wire application,
      the force required to press the prosthesis 5 mm deeper into the medullary canal
      was 0.3-2.7 times body weight. After Vitallium alloy cable application in other
      specimens, the force was 1.3-2.7 times body weight. The difference was not
      statistically significant. After monofile cerclage wire application, a force of
      1.8-8.1 times body weight was necessary to press the prosthesis 30 mm deeper into
      the medullary canal. After polyfile Vitallium alloy cable application in other
      specimens, the force was 7.7-12 times body weight. The difference was
      statistically significant (U-test, alpha < 0.025).

PMID- 10076949
TI  - Prevalence of popliteal cysts in children. A sonographic study and review of the
      literature.
AB  - Popliteal cysts in children differ from those in adults. They are considered to
      be less frequent and usually appear in the absence of intra-articular lesions.
      However, their prevalence in asymptomatic children is unknown. We present a
      prospective epidemiological study of 168 asymptomatic children under 15 years of
      age hospitalised for various pathologies. Children with knee problems and
      rheumatic diseases were excluded from the study. The children were examined
      ultrasonographically with a 7.5 MHz linear scanner. A popliteal cyst could be
      identified in 4 patients. The prevalence of asymptomatic popliteal cysts was thus
      2.4%. For 2 of these patients, we obtained magnetic resonance image of the knee
      which showed no concommitant intra-articular pathology.

PMID- 10076950
TI  - Measurement of clinical change caused by knee replacement. Conventional score or
      special change indexes?
AB  - Clinical change may be measured with specific indexes of change or with the
      difference between single-state examinations. Change scores and transition
      indexes are the special indexes of change analysed in this study. At the 10-year
      follow-up of compartmental replacements, the conformity between subsequent
      Hospital for Special Surgery overall scores and the patient's opinion of change
      from before knee replacement was 0.54. This was judged to be unacceptable. It is
      recommended that a transitional index be included in the clinical evaluation
      systems used for knee replacement.

PMID- 10076951
TI  - Conservative versus surgical treatment for femoral fracture after total or
      hemiarthroplasty of hip.
AB  - This retrospective study compared internal fixation of a femoral fracture
      following total or hemiarthroplasty of hip with conservative treatment. Sixteen
      patients were included in the study and classified according to Johannsen. Seven
      of these patients were treated conservatively by skeletal traction (group A),
      while the remaining nine patients underwent internal fixation by Mennen plate in
      conjunction with bone graft (group B). All patients were followed for at least 2
      years and evaluated clinically and radiographically using the Mayo Clinic score.
      The results of group B were superior to those of group A for fracture lines
      located proximally or extending distally to the tip of the prosthesis.
      Furthermore, two patients from group A in whom conservative treatment had failed
      underwent internal fixation, improving their final outcome. Regarding fracture
      distal to the tip of the prosthesis, there was no significant difference in final
      outcome between the groups. Our conclusion is that Mennen plate fixation should
      be considered the treatment of choice in femoral fracture around the tip of a
      prosthesis, and Mennen plate fixation for fracture distal to the tip should
      remain as a good option, especially for patients who would like to reduce the
      length of postoperative hospitalization.

PMID- 10076952
TI  - Susceptibility to local infection in biological internal fixation. Experimental
      study of open vs minimally invasive plate osteosynthesis in rabbits.
AB  - Resistance to local infection after fracture fixation with plate osteosynthesis
      may be influenced by the implantation technique. It is known that the extent of
      the surgical approach to the bone can compromise the local defence capacity. We
      have investigated susceptibility to infection after a local bacterial challenge
      in rabbit tibiae using either the open surgical approach for 'biological'
      internal fixation of standard 2.0 dynamic compression plates or the method of
      minimally invasive plate osteosynthesis (MIPO), a percutaneous, tunnelling
      insertion technique preserving the integrity of the overlying soft tissue. After
      the wounds had been closed, various concentrations of Staphylococcus aureus were
      injected in the direct vicinity of the implants. The infection rate for the open
      surgical technique was 38.5% and that for the MIPO technique, 25%. This
      difference is not statistically significant (P > 0.05) suggesting that resistance
      to local infection associated with the MIPO method is at least equivalent to the
      open approach for plate osteosynthesis.

PMID- 10076953
TI  - Arthroscopic posterior cruciate ligament reconstruction with quadriceps tendon
      patellar bone autograft.
AB  - Surgical reconstruction of the posterior cruciate ligament (PCL) is indicated in
      the PCL-deficient knee with symptomatic instability and multiple ligamentous
      injury. However, the choice of graft tissues continues to be controversial. We
      describe an arthroscopic PCL reconstruction technique using the quadriceps tendon
      patellar bone autograft. From March through September 1996, this autograft was
      used in 12 patients with PCL injuries. After 1-1.5 years' follow-up, the clinical
      outcome has been encouraging. In addition, the quadriceps tendon-patellar
      autograft has the advantage of being self-available. Furthermore, the technique
      is easy to perform and has comparable anatomic and biomechanical qualities to
      other available techniques. Quadriceps tendon-patellar autograft is a reasonable
      alternative choice for PCL reconstruction.

PMID- 10076954
TI  - Hemorrhagic shock results in intestinal muscularis intercellular adhesion
      molecule (ICAM-1) expression, neutrophil infiltration, and smooth muscle
      dysfunction.
AB  - Intestinal stasis followed by mucosal barrier breakdown and the generation of
      locally produced cytokines has been proposed as the cause of systemic infection
      and multiple organ failure following hemorrhagic shock. The aim of this study was
      to investigate the underlying mechanisms of impaired intestinal muscle function
      leading to ileus following hemorrhagic shock. Rats were subjected to severe
      hemorrhagic shock (mean arterial pressure 40 mm Hg) followed by resuscitation and
      were killed early at 4 h or late at 24 h. Other groups consisted of control and
      sham animals. Intercellular adhesion molecule (ICAM-1) mRNA levels were
      significantly elevated in the muscularis but not in the mucosa using the
      semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). There
      was a marked infiltration of neutrophils into the muscularis early and late after
      shock. Furthermore, smooth muscle contractility in response to bethanechol was
      significantly decreased, being more pronounced in the early group.
      Immunohistochemistry revealed signal for ICAM-1 in the muscularis
      microvasculature and on infiltrating cells. These results suggest that the
      expression of ICAM-1 within the muscularis vasculature after hemorrhagic shock
      promotes the local recruitment of leukocytes and that this inflammatory response
      is accompanied by a subsequent impairment of intestinal contractility.

PMID- 10076955
TI  - Lower limb amputations during 3 years in Hungary.
AB  - We reviewed nationwide hospital data of amputations during 3 years to provide a
      comparison with similar data gathered about 20 years ago. Data were provided by
      the National Medical Records Centre and processed by our personally developed
      programmes. The cause of amputation was most often vascular disease, amputees
      were usually elderly, and the large majority of amputation surgery was carried
      out on the lower limb. The rate of transtibial amputation has increased
      favourably in the last 2 decades, but there are large regional differences within
      the country. Mortality parameters remarkably exceed those of foreign countries.
      Although the data accuracy is compromised, there are still ways of exploiting the
      data in favour of quality improvement of care, e.g. improve transtibial
      amputation rate, reduce mortality. The publication of data can be of benchmarking
      importance for hospitals by enabling them to compare their own results with those
      of other hospitals, as well as to develop and improve performance.

PMID- 10076956
TI  - Wrist pain with triangular fibrocartilage thickening.
AB  - We review the case of a patient who had wrist pain with synovial proliferation
      due to triangular fibrocartilage (TFC) thickening, whose pain was relieved by
      total TFC resection. This suggested that TFC thickening should be considered in
      the evaluation of patients with wrist pain.

PMID- 10076957
TI  - Remission of idiopathic thrombocytopenic purpura after femoral lengthening.
      Clinical case followed for 5 years.
AB  - We report on a patient with chronic idiopathic thrombocytopenic purpura (ITP) who
      went into remission after femoral lengthening. Although it is possible that
      spontaneous remission (frequency 5%-10%) of chronic ITP coincided with the
      femoral lengthening, limb lengthening could also have caused the thrombocytosis.
      This case suggests a close relationship between osteogenesis and hematopoiesis
      during regenerate bone formation. Limb lengthening can therefore be defined as
      the formation not only of bone and soft tissue but also of hematopoietic tissue.

PMID- 10076958
TI  - Sciatic nerve injury associated with fracture of the femoral shaft.
AB  - The sciatic nerve escapes injury in most fractures of the femoral shaft. We
      report a case of sciatic nerve palsy associated with a fracture at the distal
      shaft of the femur. The common peroneal division of the sciatic nerve was
      lacerated by a bone fragment at the fracture site. Despite the delay in
      treatment, a satisfactory result was obtained.

PMID- 10076959
TI  - Recalcitrant bicipital radial bursitis.
AB  - Three of 12 nonrheumatoid patients with bicipital radial bursitis had recurrent
      and recalcitrant symptoms and underwent operative treatment. Preoperative
      computed tomogram showed an anterior distended synovial cyst at the level of the
      radial tubercle. Magnetic resonance imaging provided a superb demonstration of a
      bicipital radial bursa which communicated with the elbow joint below the annular
      ligament. Surgical exploration revealed a valvular mechanism between the
      distended bursa and the joint cavity. Excision of the distended bursa and closing
      the capsular defect lead to excellent results. An antecubital cyst resulting from
      an acute or chronic tear of the anterior capsule at the sacciform recess may
      communicate with the bicipital radial bursa and become the cause of recurrent and
      recalcitrant symptoms.

PMID- 10076960
TI  - Severance of the radial nerve complicating transverse fracture of the mid-shaft
      of the humerus.
AB  - A case of radial nerve injury associated with a transverse fracture of the middle
      third of the humerus is reported. The radial nerve was found to be completely
      severed at the fracture site. Early exploration of the nerve and internal
      fixation of the fracture gave a satisfactory result.

PMID- 10076961
TI  - Osteonecrosis of the femoral head associated with pregnancy.
AB  - A 31-year-old pregnant woman suddenly complained of bilateral hip pain 2 weeks
      before delivery. She was delivered of triplets by Caesarean section. She had been
      treated with human menopausal gonadotropin and human chorionic gonadotropin (hMG
      hCG) before pregnancy. Radiograms of the hip joint showed collapse of the femoral
      heads bilaterally. Magnetic resonance imaging revealed a band pattern of low
      signal intensity for both hips on T1- and T2-weighted images. She had no history
      of steroid therapy or alcohol abuse. Osteonecrosis of the femoral heads
      bilaterally associated with pregnancy was confirmed. Pathology of the femoral
      head showed typical empty lacunae and necrosis of the trabecula.

PMID- 10076962
TI  - Insufficiency fractures, an often unrecognized diagnosis.
AB  - Diagnosis of sacral insufficiency fractures is difficult since the onset is mild,
      and usually discomfort is attributed to degeneration of the lumbar spine.
      Computed tomography and radionuclide bone scans are helpful in making the
      diagnosis, as regular X-ray and magnetic resonance imaging usually fail to
      demonstrate the fracture.

PMID- 10076963
TI  - Pseudoaneurysm of the profunda femoris artery due to intertrochanteric fracture
      of the hip.
AB  - Arterial injury caused by hip fracture is a rare event. We report a case of
      pseudoaneurysm of the profunda femoris artery that presented 4 weeks after
      correction of an intertrochanteric hip fracture with a dynamic hip screw. The
      diagnosis was confirmed by Duplex ultrasound scanning, and it was treated by
      ligation of the profunda femoris artery at the level of the pseudoaneurysm.

PMID- 10076964
TI  - Non-union of undisplaced radial neck fracture in a rheumatoid patient.
AB  - Non-union of an undisplaced fracture of the radial neck in a rheumatoid patient
      is presented. Possible causes are discussed, and the literature reviewed.

PMID- 10076965
TI  - Proposition: All mammograms should be double-read.

PMID- 10076966
TI  - Intravascular brachytherapy physics: report of the AAPM Radiation Therapy
      Committee Task Group no. 60. American Association of Physicists in Medicine.
AB  - Recent preclinical and clinical studies indicate that irradiation using ionizing
      radiation in the dose range of 15 to 30 Gy may reduce the occurrence of
      restenosis in patients who have undergone an angioplasty. Several delivery
      systems of intravascular brachytherapy have been developed to deliver radiation
      doses in this range with minimal normal tissue toxicity. In late 1995 the
      American Association of Physicists in Medicine (AAPM) formed a task group to
      investigate these issues and to report the current state of the art of
      intravascular brachytherapy physics. The report of this task group is presented
      here.

PMID- 10076967
TI  - Functional fitting of interstitial brachytherapy dosimetry data recommended by
      the AAPM Radiation Therapy Committee Task Group 43. American Association of
      Physicists in Medicine.
AB  - This work was undertaken to expedite implementation of the AAPM Task Group 43
      recommendations, which call for significant modifications in the way dose is
      calculated for interstitial sources of 192Ir, 125I, and 103Pd as well as
      significant changes in the dose rate constant for 125I sources. The TG43
      recommendations include a new formalism for dose calculation at points defined by
      the radial distance, r, from the source center and the angle, theta, that such a
      radius makes with the source axis. For each source type, values are tabulated for
      the radial dose function, the anisotropy function, and the anisotropy factor. The
      TG43 report includes fitting functions for the radial dose function in the form
      of polynomials, which are poorly behaved outside the range of fitted data. No
      functions are offered for the anisotropy function data or the anisotropy factor
      data, both of which could profit from some smoothing by such functions. We have
      found a double exponential fit to the radial dose function that not only
      approximates the data adequately but also appropriately approaches zero for very
      large distances. The anisotropy function is conveniently fit with a form of type
      1 - f(r,theta)cos(theta)e(cr), which is exactly 1 at theta=90 degrees and
      approaches 1 for large r (for c<0), where f(r,theta) is a selected polynomial in
      the two variables. The form chosen for the anisotropy factor was 1 - (a+br)e(cr),
      which appropriately approaches 1 for large r (and c<0). Functional fits of these
      types are expected to facilitate implementation of TG43 recommendations, in that
      they may be either incorporated into dose algorithms or used to generate lookup
      tables of either the x, y or the r, theta format.

PMID- 10076968
TI  - Pulsed brachytherapy: a formalism to account for the variation in dose rate of
      the stepping source.
AB  - Pulsed brachytherapy is an endeavor to mimic low dose rate (LDR) treatments using
      a single higher activity source (a medium dose rate) that is periodically
      introduced into the patient (i.e., pulsed) using a remote afterloader. It has
      been reported that by a careful choice of pulse length and frequency and using
      the ERD bioeffect dose model, therapeutic advantage (TA) values slightly less
      than unity can be achieved where TA has been defined as the ratio of tumor ERD
      for PB to tumor ERD for LDR treatments for constant late-reacting normal tissue
      ERD. These calculations are based upon a uniform average dose rate in each pulse
      and equal repair rate constants for both tumor and normal tissue. In this paper,
      it is demonstrated that TAs of greater than 1 might be possible, depending upon
      the repair rate constants assumed for the tissues involved. Furthermore, for PB
      treatments the dose rate at a point of interest during each pulse is not uniform,
      since the treatment involves a single stepping source. A generalized ERD equation
      based on the linear quadratic model has been developed to account for the
      variation in the dose rate and, subsequently, to maximize the TA. Our
      calculations indicate that PB performed with 40 pulses in 120 hours with an
      irradiation time of 30 minutes per pulse with a delay time of two and a half
      hours is the best replacement for a LDR treatment that delivers 60 Gy in 120
      hours.

PMID- 10076969
TI  - Quality assurance for the Leksell gamma unit: considering magnetic resonance
      image-distortion and delineation failure in the targeting of the internal
      auditory canal.
AB  - Our aim in this study was to distinguish quantitatively between the localization
      accuracy of a commercially available stereotactic fixation device as claimed by
      the manufacturer and the target accuracy as measured by a user, applying
      neuroradiologic imaging in Gamma Knife planning and phantom irradiation. Missing
      the target is the most serious possible failure in Gamma Knife and Linac therapy.
      To reduce this risk, we developed a quality control algorithm and designed a
      phantom. To evaluate the accuracy of the targeting procedure with a Leksell Gamma
      unit, and to experience the possible errors in all procedural steps, irradiations
      of phantoms were performed, using the so-called "unknown" targeting method.
      Accuracy is defined by the extent of spatial deviation of the irradiated target
      from the calculated target. Digital imaging was used for therapy planning.
      GafChromic films, which had been irradiated while affixed to a specially
      developed phantom, were used for measuring the precision of the radiation unit. A
      series of MR images (in two plains: transverse and coronal) was acquired
      sequentially to image the three-dimensional (3-D) volume of the phantom. The
      results obtained for isocentric accuracy of the Leksell Gamma unit, model B, were
      in good agreement to the calculated position. The observed spatial deviations
      between calculated and irradiated targets is less than 1 mm. The newly designed
      phantom and quality control algorithm are useful in quality assurance
      measurements of stereotactic radiation therapy.

PMID- 10076970
TI  - The importance of computed tomography slice thickness in radiographic patient
      positioning for radiosurgery.
AB  - A new radiographic patient positioning technique developed for radiosurgery has
      been analyzed to show the effect of computed tomography (CT) slice thickness on
      the precision of target localization during treatment. The positioning technique
      establishes the pose of the patient's anatomy during treatment by comparing
      treatment room radiographs with digitally reconstructed radiographs derived from
      a CT study. The measured pose is then used to align the x-ray therapy beam with
      the treatment site, without resorting to mechanical fixation. The technique has
      been found to be sensitive to submillimeter changes in skull position, which is
      the level of precision desired for radiosurgery. In this report it is shown that
      the precision of head localization improves by a factor of 2 when the CT slice
      thickness is reduced from 3.0 to 1.5 mm. This indicates that, in radiosurgical
      applications, image-guided beam alignment can be significantly influenced by the
      spatial resolution of the reference CT study. This result is relevant to all high
      precision radiographic positioning techniques that utilize CT images.

PMID- 10076971
TI  - Multileaf collimator interleaf transmission.
AB  - Multileaf collimators (MLCs) have advanced past their original design purpose as
      a replacement for field shaping cerrobend blocks. Typically, MLCs incorporate an
      interlocking tongue-and-groove design between adjacent leaves to minimize leakage
      between leaves. They are beginning to be used to provide intensity modulation for
      conformal three-dimensional radiation therapy. It is possible that a critical
      target volume may receive an underdose due to the region of overlap if adjacent
      leaves are allowed to alternate between the open and closed positions, as they
      might if intensity modulation is employed. This work demonstrates the magnitude
      of that effect for a commercially available one-dimensional temporally modulated
      MLC. The magnitude of the transmission between leaves as a function of leaf
      separation was also studied, as well as the transmission as a function of leaf
      rotation away from the source. The results of this work were used for the design
      of a tomotherapy MLC. The radiation leakage considerations for a tomotherapy MLC
      are discussed.

PMID- 10076972
TI  - Theoretical considerations of monitor unit calculations for intensity modulated
      beam treatment planning.
AB  - A treatment planning system to compute intensity modulated radiotherapy (IMRT)
      treatments using inverse planning was investigated. The system was designed to
      optimize the intensity patterns required to treat a specified target volume with
      specified normal structure constraints. A beam model that uses the convolution of
      pencil beams was used to compute the dose distributions. A multileaf collimator
      leaf-setting sequence intended to produce the intensity pattern was computed
      along with the monitor units required to deliver each of a number of fixed-gantry
      modulated fields. Computer calculations are commonly verified using an
      independent manual procedure. It is difficult to calculate treatment delivery
      monitor units for this variant of IMRT using manual methods. Since manual
      calculations are not feasible, it is important both to understand and to verify
      the calculation of treatment monitor units by the planning system algorithm. A
      formal analysis was made of the dose calculation model and the monitor unit
      calculation embedded in the algorithm. Experimental verification of the dose
      delivered by plans computed with the methodology demonstrated an agreement of
      better than 4% between the dose model and measurements.

PMID- 10076973
TI  - Incorporation of functional status into dose-volume analysis.
AB  - The dose-volume histogram (DVH) has gained wide acceptance as a mechanism for
      reducing the voluminous data of a three-dimensional dose distribution into a two
      dimensional graph. These graphs are often converted to a single figure of merit.
      This data reduction technique is used both for clinical treatment plan evaluation
      and as part of proposed systems for estimating control and complication
      probabilities. It has long been recognized that a major shortcoming of the DVH as
      an analysis tool is that all spatial information is discarded. A subtler problem,
      which is addressed in this work, is that the DVH also implies homogeneity of
      biological consequence of irradiation in what may be a functionally heterogeneous
      volume of tissue. An extension to the DVH, the functional dose-volume histogram,
      or dose-function histogram (DFH), is proposed, that explicitly includes
      quantitative three-dimensional functional information. The concept is illustrated
      by the use of SPECT imaging to assess the functional status of irradiated lung.

PMID- 10076974
TI  - Determination of scatter factor parameters and electron disequilibrium for
      monoenergetic photon beams.
AB  - The tissue-phantom-ratio (TPR) is expressed as the product of the phantom scatter
      factor (SF), an electron disequilibrium factor, and an attenuation factor, equal
      to the zero-area TPR. The scatter factor, as a function of depth d and field size
      s, has been described by two parameters a and w, SF(d,s) = 1 + asd/(ws + d). We
      have determined the parameters a and w for 20 monoenergetic photon beams between
      1 and 20 MeV. Pencil-beam energy-deposition kernels were obtained using Monte
      Carlo simulations. The kernels were used to calculate broad-beam depth-dose data,
      which were converted to TPR and fitted to the equation above using an iterative
      search over a-w space. The parameter a is nearly equal to the attenuation
      coefficient for all energies while the parameter w increases with energy. The
      resulting a and w compare favorably to values determined for clinical photon
      beams, as a function of the measured attenuation coefficient. With the scatter
      factor determined, we isolated the electron disequilibrium factor for each
      monoenergetic beam. It can be characterized as a quadratic function of the depth.
      The coefficients of the quadratic function can be related to the range of the
      most energetic secondary electron produced.

PMID- 10076975
TI  - Room scattered neutrons.
AB  - A method of evaluating the photoneutron fluence in the maze of accelerator
      facilities due to room scattered neutrons is presented. Measurements were made to
      demonstrate that the room scattered fluence is reduced by a factor of 2pi in
      going from the treatment room to the inner maze entrance.

PMID- 10076976
TI  - Measured overall perturbation factors at depths greater than dmax for ionization
      chambers in electron beams.
AB  - In electron beam dosimetry the perturbation effect in the medium by the
      ionization chamber cavity is accounted for by introducing a replacement
      correction factor, P(repl). Another perturbation correction factor, denoted as
      P(wall), is due to the materials of the walls of the parallel-plate chamber
      differing from the phantom material. Because of the difficulties in separating
      these two components, we measure the overall perturbation factor, p(q) =
      P(repl)P(wall). A distinct advantage of parallel-plate ionization chambers over
      cylindrical chambers is that p(q) has been shown to be close to unity at the
      standard calibration depth, d(max). However, for many dosimetry applications it
      is necessary to know the overall perturbation factor at depths greater than
      d(max). We measured the overall perturbation factor at depths greater than d(max)
      (approximating the 95%, 90% and 50% depth dose) for a Farmer-type cylindrical
      ionization chamber and three parallel-plate ionization chambers. We assumed that
      p(q) for the NACP chamber is unity at these measurement depths. The depth
      dependence for the other chambers was then measured relative to the NACP chamber.
      The mean energy at depth, E(d), and percentage depth dose gradient ranges studied
      were 1.9-18.5 MeV and 0 to 4.5%/mm, respectively. For the other two parallel
      plate chambers, we find p(q) to be unity at depths where the percent depth dose
      is greater than 90%, but it deviates from unity at deeper depths, where the dose
      gradients exceed about 2.5%/mm. For the cylindrical chamber, p(q) values at
      depths greater than d(max) were found to be in good agreement with those in TG
      21, where the energy at depth, E(d), is used to evaluate p(q).

PMID- 10076977
TI  - Ionization chamber, electrometer, linear accelerator, field size, and energy
      dependence of the polarity effect in electron dosimetry.
AB  - Plane-parallel ionization chambers are the instrument of choice for use in
      electron calibration and dosimetry, but these chambers may exhibit large polarity
      effects. This study concentrates on measuring the dependence of the polarity
      error at various mean energies using different linear accelerator, field size,
      ion chamber, and electrometer combinations. The polarity error was shown to
      increase for all four ionization chambers as the mean energy at depth decreased,
      but was always less than one percent at d(max). Polarity error dependence was
      also observed for similar plane-parallel chambers, varying field sizes, and
      different linear accelerators, but no polarity error dependence was observed for
      similar cylindrical chambers and different electrometers. Measurements of the
      polarity error can be used to develop correction factors for future measurements
      that will help minimize the time spent performing electron dosimetry and
      calibrations. These correction factors can be used to calculate the correct
      reading without the need to reverse the chamber bias, thus reducing the number of
      measurements required.

PMID- 10076978
TI  - The flatness of Siemens linear accelerator x-ray fields.
AB  - The primary definer for Siemens MXE and MDX linear accelerators projects a
      circular opening with a radius of 25 cm at 100 cm from the target. Our
      measurements of photon beam profiles, however, indicate that the photon fluence
      drops to 95% of the central axis value at a radius of 18 cm. The flattening
      filter for these machines projects a flattened field size that is much smaller
      than the primary definer would allow. The clinical implications of this mismatch
      for large rectangular fields and for fields defined by asymmetric jaws are
      discussed and solutions are considered. A large field flattener was designed for
      our Siemens MXE 6 MV beam using Monte Carlo simulation of the treatment head and
      water phantom. The accuracy required of source and geometry details for dose
      distributions calculation is presented. The key parameters are the mean energy
      and focal spot size of the electron beam incident on the exit window, the
      material composition, and thickness profile of the exit window, target,
      flattener, and primary collimator, and the position of the primary collimator
      relative to the target. Profiles were more sensitive than central axis depth
      doses to simulation details. The beam energy and primary collimator position were
      selected to achieve good agreement between measured and calculated dose
      distributions. The flattener we designed with Monte Carlo was machined from brass
      and mounted on our MXE treatment unit. Measurements demonstrate that the large
      field flattener extends the useful radius of the field out to 22 cm, right into
      the penumbra cast by the primary collimator.

PMID- 10076979
TI  - A method of beam-couch intersection detection.
AB  - At the time of treatment planning it would be useful to know whether part of the
      treatment beam passes through the patient/couch support assembly before it passes
      through the patient. In the previous work of Yorke, the range of gantry angles
      leading to beam-couch intersection was found as a function of couch translation
      for symmetric field sizes and for zero couch rotation. Yorke's method has been
      extended to include couch rotation, dual independent jaws, and multi-leaf
      collimator (MLC) field shapes. In addition, the new method is also applicable in
      the situation of the couch top located above the isocenter. For a clinically
      treatable, 20 x 20 cm field configuration in a linac, the range of gantry angles
      leading to beam-couch intersection are different by 6.7 degrees for a couch
      rotation angle of 25 degrees when compared to no couch rotation. The new method
      agrees with data within the setup and measurement uncertainties for a variety of
      field sizes including an oval shaped MLC field, and various couch locations,
      couch, and collimator rotation angles.

PMID- 10076980
TI  - Designing an optical distance indicator for a radiation therapy accelerator.
AB  - The computational aspects of the design of an optical distance indicator (ODI)
      for use with a radiation therapy accelerator are discussed. The specifics of the
      optical and mechanical design of an ODI for use with a superconducting cyclotron
      used for fast neutron therapy are presented.

PMID- 10076981
TI  - A test tool for the visual verification of light and radiation fields using film
      or an electronic portal imaging device.
AB  - We describe the design and evaluation of a simple test tool which can be used in
      conjunction with either film or an electronic portal imaging device (EPID) to
      verify light and radiation fields and their congruence. The precision of the
      technique is better than 0.5 mm under all conditions tested. When used with film
      the accuracy or offset of the technique (the difference between test tool
      observations and a scanned conventional film) is better than 0.5 mm but, with an
      EPID as the image receptor, the accuracy dropped to, in one trial, 0.86 mm. The
      offset may be due to a systematic observer bias in determining the 50% O.D. level
      on the image, compounded, in the case of EPID measurements, by image acquisition
      and display parameters. Thus, when used with an EPID, calibration of the system
      will be required if absolute field dimensions are required. When used with film,
      the test tool method described here is of sufficient accuracy and precision to
      confirm the compliance of light and radiation field parameters with currently
      accepted quality control protocols.

PMID- 10076982
TI  - An artificial neural net and error backpropagation to reconstruct single photon
      emission computerized tomography data.
AB  - At present, algorithms used in nuclear medicine to reconstruct single photon
      emission computerized tomography (SPECT) data are usually based on one of two
      principles: filtered backprojection and iterative methods. In this paper a
      different algorithm, applying an artificial neural network (multilayer
      perception) and error backpropagation as training method are used to reconstruct
      transaxial slices from SPECT data. The algorithm was implemented on an Elscint
      XPERT workstation (i486, 50 MHz), used as a routine digital image processing tool
      in our departments. Reconstruction time for a 64 x 64 matrix is approximately 45
      s/transaxial slice. The algorithm has been validated by a mathematical model and
      tested on heart and Jaszczak phantoms. Phantom studies and very first clinical
      results ((111)In octreotide SPECT, 99mTc MDP bone SPECT) show in comparison with
      filtered backprojection an enhancement in image quality.

PMID- 10076983
TI  - Kinetics of 76Br-labeled anti-CEA antibodies in pigs; aspects of dosimetry and
      PET imaging properties.
AB  - A monoclonal antibody labeled with the positron-emitting radionuclide 76Br
      (T(1/2) 16.2 h) has previously been shown useful for positron emission tomography
      (PET) imaging of experimental tumors. Our aim in the present study was to
      investigate the effects of the complex decay scheme of this radionuclide on
      normal organ dosimetry and PET image quality. Three mini-pigs were injected
      intravenously with 46-75 MBq of the 76Br-labeled anti-CEA antibody 38S1, and the
      whole-body kinetics followed by PET imaging for 19 h. From PET data, absorbed
      doses in human organs were estimated using the MIRDOSE 3.0 software. The highest
      76Br concentrations were found in lungs, after a correction for the air volume in
      this organ. The lungs received the highest absorbed dose (mGy/MBq, mean+/-maximum
      error), 0.84+/-0.16, followed by liver, 0.74+/-0.28, and small intestine, 0.55+/
      0.05, while the effective dose equivalent was 0.41+/-0.03 mSv/MBq. The PET
      imaging properties of 76Br in a two-dimensional 2D PET camera, including central
      area resolution and scattering effects, were investigated in phantoms and
      compared to those of 18F. In a 0.97 g/cm3 material, approximating soft tissue
      density, the FMHW ("full width at half-maximum") value of the point spread
      function was 7.7+/-0.2 mm for 76Br and 6.0+/-0.1 mm for 18F. In conclusion,
      radioimmuno PET using 76Br-labeled antibodies resulted in a fairly even
      distribution of the radiation dose, where the highest absorbed organ doses were
      only about two to three times higher than the mean absorbed body dose. The high
      energy beta+ spectrum in the 76Br decay had only minor effects on the resolution,
      but may decrease the quantification accuracy, especially in organs with a lower
      density such as a lung.

PMID- 10076984
TI  - Half-value layer and intensity variations as a function of position in the
      radiation field for film-screen mammography.
AB  - Differences in half-value layer (HVL) and radiation intensity are investigated as
      a function of position in the mammographic radiation field. Sources of systematic
      variation include the heel effect, the inverse square law, and differential
      photon path lengths through thicknesses of inherent and added filtration. The
      combination of these effects can increase the HVL by as much as 9% and reduce
      intensity by as much as 40% along the cathode-anode axis. To the left and right
      of the x-ray field central axis, reductions in radiation intensity of up to 9%
      and minor increases in HVL are noted as well. Optical density variations as a
      function of position in the field correlate well with the measured radiation
      intensity changes.

PMID- 10076985
TI  - Evaluating the performance of detection algorithms in digital mammography.
AB  - The initial and relative evaluation of computer methodologies developed for
      assisting diagnosis in mammography is usually done by comparing the computer
      output to ground truth data provided by experts and/or biopsy. Reported studies,
      however, give little information on how the performance indices of computer
      assisted diagnosis (CAD) algorithms are determined in this initial stage of
      evaluation. Several strategies exist in the estimation of the true positive (TP)
      and false positive (FP) rates with respect to ground truth. Adopting one strategy
      over another yields different performance rates that can be over- or
      underestimates of the true performance. Furthermore, the estimation of pairs of
      TP and FP rates gives a partial picture of the performance of an algorithm. It is
      shown in this work that new performance indices are needed to fully describe the
      degree of detection (part or whole) and the type of detection (single
      calcification, cluster of calcifications, mass, or artifact). Several evaluation
      strategies were tested. The one that yielded the most realistic performances
      included the following criteria: The detected area should be at least 50% of the
      true area and no more than four times the true area in order to be considered TP.
      At least three true calcifications should be detected to within 1 cm2 with
      nearest neighbor distances of less than square root(2) cm for a cluster to be
      considered TP. Separate detection measures should be established and used for
      artifacts and naturally occurring structures to maximize the benefits of the
      evaluation. Finally, it is critical that CAD investigators provide information on
      the tested image set as well as the criteria used for the evaluation of the
      algorithms to allow comparisons and better understanding of their methodologies.

PMID- 10076986
TI  - Reduced partial volume artifacts using spiral computed tomography and an
      integrating interpolator.
AB  - A technique is described for obtaining computed tomography (CT) head images with
      significantly reduced partial volume artifacts while retaining excellent low
      contrast resolution. Partial volume artifacts could be reduced by narrowing the
      collimation and summing thin slices. However, in axial scans, the acquisition and
      reconstruction time required for generating all the thin slices would prove
      clinically impractical. In addition, image artifacts could occur due to patient
      motion during the scans, particularly in trauma cases. In the case of spiral CT,
      a narrow collimation along with a small pitch can be used to reduce partial
      volume artifacts. However, the time required to reconstruct and sum the thin
      slices is still prohibitive. In this paper, we present a spiral technique using
      an integrating spiral interpolator (ISI) that allows a head study to be performed
      in less time without the partial volume artifacts normally seen. Using this
      interpolator, thick slices can be prospectively reconstructed from a spiral scan
      with a narrow collimation. The slice sensitivity profile for this interpolator
      was obtained and the full width at half-maximum and full width at tenth-maximum
      values were compared with both axial and predicted values. Noise values were also
      measured and compared to axial and theoretical predictions. Using this ISI
      interpolator, high quality head images were obtained with significantly reduced
      partial volume artifacts compared to standard axial and spiral scans. Total
      acquisition time is less than that of standard contiguous axial head scans.

PMID- 10076987
TI  - Experimental determination of section sensitivity profiles and image noise in
      electron beam computed tomography.
AB  - To determine the effect of continuous-volume scanning (CVS) on z-axis resolution,
      section sensitivity profiles were measured on an electron beam computed
      tomography (CT) scanner and compared with those obtained using the step-volume
      scanning (SVS) mode. A steel bead was imaged using different scan parameters, and
      the mean CT number over the bead was plotted against the z-axis position to
      determine section sensitivity profiles. From these profiles, full width at half
      maximum (FWHM), full width at tenth maximum (FWTM), and full width at tenth area
      (FWTA) were calculated. A uniform water phantom was imaged to measure noise. To
      determine the visual significance of changes in the section sensitivity profile,
      a section thickness and contiguity phantom was imaged. All section sensitivity
      profiles measured had an FWHM value within 0.5 mm of the nominal scan width. The
      FWTM and FWTA values increased with the CVS mode compared with the SVS mode. This
      broadening of the section sensitivity profiles was most significant with larger
      collimator widths. However, use of smaller collimator widths increased image
      noise. When all other parameters remained constant, increasing the exposure time
      to reduce image noise did not affect the section sensitivity profile. The CVS
      mode produced wider section sensitivity profiles than the SVS mode. This effect
      was minimized when the smallest collimator width was used, but at the expense of
      increased image noise.

PMID- 10076988
TI  - New low-contrast resolution phantoms for computed tomography.
AB  - Computed tomography (CT) has been established as a major imaging modality in
      diagnostic radiology. Accordingly, acceptance testing and quality control of CT
      scanners is of great importance. While most procedures and phantoms for testing
      are widely accepted, there is still discussion and uncertainty about low-contrast
      (LC) sensitivity. In our opinion this unsatisfactory situation is caused at least
      in part by the lack of suitable phantoms for LC resolution measurements. We
      investigated the commonly used phantoms for LC detectability, the Catphan, and
      for LC resolution, the ATS phantom. While the Catphan showed stable object
      contrasts, the ATS phantom's measured contrast exhibited a strong dependence on
      temperature and x-ray quality. Based on newly developed polyurethane resin
      materials, we designed and tested a LC resolution phantom with several different
      contrast steps. The object contrasts showed no dependence on temperature and beam
      quality. The new LC resolution phantom proved to be very suitable for measuring a
      scanner's low-contrast sensitivity in the image plane, one of the most important
      image quality parameters. To assess LC resolution in three dimensions we designed
      an additional phantom with rows of spherical objects. A first prototype was
      evaluated in a multicenter study. The setup proved to be very helpful to quantify
      the in-plane and axial LC sensitivity of spiral CT scan modes.

PMID- 10076989
TI  - Off-axis x-ray spectra: a comparison of Monte Carlo simulated and computed x-ray
      spectra with measured spectra.
AB  - The off-axis x-ray spectra from a constant potential x-ray generator were
      measured with a high purity germanium spectrometer cooled to liquid nitrogen
      temperature. The measured spectra were compared with off-axis x-ray spectra
      calculated using a code based on the semiempirical model developed by Tucker et
      al. and Monte Carlo simulated x-ray spectra using the EGS4 code system. In this
      study, both the Tucker model, and the EGS4 code system, were found to produce off
      axis bremsstrahlung x-ray spectra which agreed well with the spectra measured at
      three emerging angles. In the measured and the EGS4 generated spectra the total K
      characteristic peaks were in increasing order, as observed in the anode to
      cathode direction, whereas the Tucker model produced maximum total K
      characteristic peaks at the 6 degrees anode side, and lesser amounts at the
      central axis and the 6 degrees cathode side. Large differences in the total K
      characteristic lines is seen among the three different methods. The EGS4 code
      system was able to produce x-ray spectra for a combination of target materials.

PMID- 10076990
TI  - Maximum likelihood estimation in calibrating a stereo camera setup.
AB  - Motion and deformation of the cardiac wall may be measured by following the
      positions of implanted radiopaque markers in three dimensions, using two x-ray
      cameras simultaneously. Regularly, calibration of the position measurement system
      is obtained by registration of the images of a calibration object, containing 10
      20 radiopaque markers at known positions. Unfortunately, an accidental change of
      the position of a camera after calibration requires complete recalibration.
      Alternatively, redundant information in the measured image positions of stereo
      pairs can be used for calibration. Thus, a separate calibration procedure can be
      avoided. In the current study a model is developed that describes the geometry of
      the camera setup by five dimensionless parameters. Maximum Likelihood (ML)
      estimates of these parameters were obtained in an error analysis. It is shown
      that the ML estimates can be found by application of a nonlinear least squares
      procedure. Compared to the standard unweighted least squares procedure, the ML
      method resulted in more accurate estimates without noticeable bias. The accuracy
      of the ML method was investigated in relation to the object aperture. The
      reconstruction problem appeared well conditioned as long as the object aperture
      is larger than 0.1 rad. The angle between the two viewing directions appeared to
      be the parameter that was most likely to cause major inaccuracies in the
      reconstruction of the 3-D positions of the markers. Hence, attempts to improve
      the robustness of the method should primarily focus on reduction of the error in
      this parameter.

PMID- 10076991
TI  - Computational techniques for fast hyperthermia temperature optimization.
AB  - Hyperthermia temperature optimization involves arriving at a temperature
      distribution which minimizes a stated goal function, the goal function having a
      biological basis in maximizing tumor cell kill while not exceeding normal tissue
      toxicity. This involves the computationally intensive process of multiple
      evaluations of the temperature goal function, requiring repeated evaluations of
      the power deposition and its corresponding temperature distribution. Two
      computational schemes are proposed to expedite the temperature optimization
      process: (1) temperature distribution evaluation by superpositioning precomputed
      distributions, and (2) using representative tissue groups (rather than every
      point in the domain) to evaluate the goal function. The application of these
      schemes is illustrated with a typical optimization problem, as applied to
      symmetric and asymmetric, heterogeneous models. Application of these schemes
      reduced the optimization time on a DEC Alpha 1000 4/266 (Alpha is a registered
      trademark of Digital Equipment Corporation.) from several h to min, with little
      difference in results. The computational schemes, though demonstrated in the
      context of electromagnetic hyperthermia, are generally applicable to other forms
      of nonionizing radiation employed in hyperthermia therapy.

PMID- 10076992
TI  - How much does film sensitivity increase at depth for larger field sizes?

PMID- 10076993
TI  - Chromatin recycling of glucocorticoid receptors: implications for multiple roles
      of heat shock protein 90.
AB  - Unliganded glucocorticoid receptors (GRs) released from chromatin after hormone
      withdrawal remain associated with the nucleus within a novel subnuclear
      compartment that serves as a nuclear export staging area. We set out to examine
      whether unliganded nuclear receptors cycle between distinct subnuclear
      compartments or require cytoplasmic transit to regain hormone and chromatin
      binding capacity. Hormone-withdrawn rat GrH2 hepatoma cells were permeabilized
      with digitonin to deplete cytoplasmic factors, and then hormone-binding and
      chromatin-binding properties of the recycled nuclear GRs were measured. We found
      that recycled nuclear GRs do not require cytosolic factors or ATP to rebind
      hormone. Nuclear GRs that rebind hormone in permeabilized cells target to high
      affinity chromatin-binding sites at 30 C, but not 0 C, in the presence of ATP.
      Since geldanamycin, a heat shock protein-90 (hsp90)-binding drug, inhibits
      hormone binding to recycled nuclear GRs, hsp90 may be required to reassemble the
      receptor into a form capable of productive interactions with hormone.
      Geldanamycin also inhibits GR release from chromatin during hormone withdrawal,
      suggesting that hsp90 chaperone function may play multiple roles to facilitate
      chromatin recycling of GR.

PMID- 10076994
TI  - Differential localization and activity of the A- and B-forms of the human
      progesterone receptor using green fluorescent protein chimeras.
AB  - Subcellular localization and transcriptional activity of green fluorescent
      protein-progesterone receptor A and B chimeras (GFP-PRA and GFP-PRB) were
      examined in living mammalian cells. Both GFP-PRA and B chimeras were found to be
      similar in transcriptional activity compared with their non-GFP counterparts. GFP
      PRA and PRA were both weakly active, while GFP-PRB and PRB gave a 20- to 40-fold
      induction using a reporter gene containing the full-length mouse mammary tumor
      virus long-terminal repeat linked to the luciferase gene (pLTRluc). Using
      fluorescence microscopy, nuclear/cytoplasmic distributions for the unliganded and
      hormone activated forms of GFP-PRA and GFP-PRB were characterized. The two forms
      of the receptor were found to have distinct intracellular distributions; GFP-PRA
      was found to be more nuclear than GFP-PRB in four cell lines examined. The causes
      for and implications of this differential localization of the A and B forms of
      the human PR are discussed.

PMID- 10076995
TI  - Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an
      androgen response element in the proximal promoter.
AB  - Androgen is essential for the physiological maintenance of the integrity of
      prostatic epithelial cells, and castration causes the cells to undergo apoptosis.
      To study the molecular mechanism of androgen-dependent cell growth, we showed
      that androgen up-regulates the expression of the cyclin-dependent kinase
      inhibitor p21 (WAF1, CIP1, SDI1, CAP20) gene at both the mRNA and protein levels.
      Nuclear run-on assays demonstrated that androgen stimulates endogenous p21 gene
      expression at the transcriptional level. Transient transfection experiments
      showed that androgen can enhance the activity of a 2.4-kb promoter of the p21
      gene linked to a luciferase reporter. These results suggested that a putative
      androgen response element (ARE), which mediates androgen response to enhance the
      p21 transcription, is included in the 2.4-kb promoter fragment. Deletion analysis
      of the promoter revealed a functional ARE (AGCACGCGAGGTTCC) located at -200 bp of
      the p21 gene proximal to the promoter region. Electrophoretic mobility shift
      assay further demonstrated that the androgen receptor specifically binds to this
      element. Wild-type ARE, but not mutant ARE, confers androgen responsiveness to a
      heterologous promoter. The up-regulation of p21 gene expression by androgen
      suggests that p21 may have an antiapoptotic function in prostatic epithelial
      cells. However, this hypothesis will need to be tested in future experiments.

PMID- 10076996
TI  - Identification of a placental-specific enhancer in the rat placental lactogen II
      gene that contains binding sites for members of the Ets and AP-1 (activator
      protein 1) families of transcription factors.
AB  - We previously identified a 3-kb proximal 5'-flanking region of the rat placental
      lactogen (rPLII) gene that is important for reporter gene transcription in the
      rat trophoblast cell line, Rcho, and targets expression to the placentas of
      transgenic mice. In our current studies we have used further deletion analysis
      and transfection studies in Rcho and GC cells to map more precisely the locations
      of regulatory elements involved in this placental expression. We show that
      sequences between - 1435 and -765 are necessary for minimal expression in Rcho
      cells and that there are negative regulatory elements between -3031 to -2838 and 
      1729 to -1435. Most importantly, we have identified a fragment between -1793 to 
      1729 that is essential for expression levels characteristic of the complete 3-kb
      5'-region. When linked to the herpes simplex thymidine kinase minimal promoter,
      this fragment acts as an enhancing element in Rcho but not GC cells.
      Deoxyribonuclease I (DNAse I) protection and electrophoretic mobility shift
      assays with nuclear extracts and in vitro translated proteins identify binding
      sites for members of the activator protein-1 (AP-1) and Ets families of
      transcription factors. Site-directed mutagenesis of the individual AP-1- and Ets
      binding sites leads to a partial loss of the enhancing activity; a double AP
      1/Ets mutation leads to a complete loss of activity, demonstrating the functional
      importance of these sites. By these criteria, putative GATA-binding sites located
      within the enhancing fragment are not active. These new data suggest an important
      role for this enhancing fragment in rPLII placental giant cell expression and are
      the first to implicate a member of the Ets family in the regulation of this gene
      family.

PMID- 10076997
TI  - Fibrates increase human REV-ERBalpha expression in liver via a novel peroxisome
      proliferator-activated receptor response element.
AB  - Fibrates are widely used hypolipidemic drugs that act by modulating the
      expression of genes involved in lipid and lipoprotein metabolism. Whereas the
      activation of gene transcription by fibrates occurs via the nuclear receptor
      peroxisome proliferator-activated receptor-alpha (PPARalpha) interacting with
      response elements consisting of a direct repeat of the AGGTCA motif spaced by one
      nucleotide (DR1), the mechanisms of negative gene regulation by fibrates and
      PPARalpha are largely unknown. In the present study, we demonstrate that fibrates
      induce the expression of the nuclear receptor Rev-erbalpha, a negative regulator
      of gene transcription. Fibrates increase Rev-erbalpha mRNA levels both in primary
      human hepatocytes and in HepG2 hepatoblastoma cells. In HepG2 cells, fibrates
      furthermore induce Rev-erbalpha protein synthesis rates. Transfection studies
      with reporter constructs driven by the human Rev-erbalpha promoter revealed that
      fibrates induce Rev-erbalpha expression at the transcriptional level via
      PPARalpha. Site-directed mutagenesis experiments identified a PPAR response
      element that coincides with the previously identified Rev-erbalpha negative
      autoregulatory Rev-DR2 element. Electromobility shift assay experiments indicated
      that PPARalpha binds as heterodimer with 9-cis-retinoic acid receptor to a subset
      of DR2 elements 5' flanked by an A/T-rich sequence such as in the Rev-DR2.
      PPARalpha and Rev-erbalpha bind with similar affinities to the Rev-DR2 site. In
      conclusion, these data demonstrate human Rev-erbalpha as a PPARalpha target gene
      and identify a subset of DR2 sites as novel PPARalpha response elements. Finally,
      the PPARalpha and Rev-erbalpha signaling pathways cross-talk through competition
      for binding to those response elements.

PMID- 10076998
TI  - A novel method for analysis of nuclear receptor function at natural promoters:
      peroxisome proliferator-activated receptor gamma agonist actions on aP2 gene
      expression detected using branched DNA messenger RNA quantitation.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the
      nuclear hormone receptor superfamily, plays an essential role in the mediation of
      the actions of antidiabetic drugs known as thiazolidinediones (TZDs). PPARgamma
      activates many target genes involved in lipid anabolism including the adipocyte
      fatty acid binding protein (aP2). In this study, induction of aP2 gene expression
      by PPARgamma agonists was examined in both cultured cells and diabetic mice using
      branched DNA (bDNA)-mediated mRNA quantitation. bDNA technology allows for the
      direct measurement of a particular mRNA directly within cellular lysate using a
      96-well plate format in a time frame comparable to a reporter gene assay. In
      cultured human subcutaneous preadipocytes, the TZDs, troglitazone and BRL-49653,
      both rapidly induced aP2 mRNA as detected with the bDNA method. In these cells,
      the effect of BRL-49653 on aP2 mRNA levels was detectable as early as 30 min
      after treatment (47% increase) and was maximal after 24 h of treatment (12-fold
      increase). The effects of troglitazone on aP2 mRNA induction were similar to
      those of BRL-49653 except that the maximal level of induction was consistently
      lower (e.g. 24 h treatment = 4-fold increase). Dose-response relationships for
      both of the TZDs were also determined using the 24-h treatment time point. EC50s
      for both BRL-49653 and troglitazone were estimated to be 80 nM and 690 nM,
      respectively. A natural PPARgamma ligand, 15-deoxy-delta12,14-PGJ2, was also
      active in this assay with a maximal induction of aP2 mRNA of approximately 5-fold
      when tested at 1 microM. Since the PPARgamma:retinoid X receptor (RXR)
      heterodimer has been characterized as a permissive heterodimer with respect to
      RXR ligands, the ability of 9-cis-retinoic acid (9-cis-RA) to induce aP2 mRNA was
      examined. Although 9-cis-RA had very low efficacy (2-fold induction), the maximal
      effect was reached at 100 nM. No synergism or additivity in aP2 mRNA induction
      was detected when 9-cis-RA was included with either of the TZDs used in this
      study. Significant induction of aP2 mRNA in bone marrow of db/db mice treated
      with either troglitazone or BRL-49653 was also detected, indicating that the bDNA
      assay may be a simple method to monitor nuclear receptor target gene induction in
      vivo.

PMID- 10076999
TI  - Estrogen receptor beta activates the human retinoic acid receptor alpha-1
      promoter in response to tamoxifen and other estrogen receptor antagonists, but
      not in response to estrogen.
AB  - Human estrogen receptor-alpha (hERalpha) or -beta (hERbeta) transfected into Hep
      G2 or COS1 cells each responded to estrogen to increase transcription from an
      estrogen-responsive element (ERE)-driven reporter vector with similar fold
      induction through a classical mechanism involving direct receptor binding to DNA.
      ER antagonists inhibited this estrogen induction through both hERalpha and
      hERbeta, although raloxifene was more potent through ERalpha than ERbeta, and
      tamoxifen was more potent via ERbeta than ERalpha. We have shown previously that
      estrogen stimulated the human retinoic acid receptor-alpha-1 (hRARalpha-1)
      promoter through nonclassical EREs by a mechanism that was ERalpha dependent, but
      that did not involve direct receptor binding to DNA. We show here that in
      contrast to hERalpha, hERbeta did not induce reporter activity driven by the
      hRARalpha-1 promoter in the presence of estrogen. While hERbeta did not confer
      estrogen responsiveness on this promoter, it did elicit transcriptional
      activation in the presence of 4-hydroxytamoxifen (4-OH-Tam). Additionally, this 4
      OH-Tam agonist activity via ERbeta was completely blocked by estrogen. Like
      ERalpha, transcriptional activation of this promoter by ERbeta was not mediated
      by direct receptor binding to DNA. While hERalpha was shown to act through two
      estrogen-responsive sequences within the promoter, hERbeta acted only at the 3'
      region, through two Sp1 sites, in response to 4-OH-Tam. Other ER antagonists
      including raloxifene, ICI-164,384 and ICI-182,780 also acted as agonists through
      ERbeta via the hRARalpha-1 promoter. Through the use of mutant and chimeric
      receptors, it was shown that the 4-OH-Tam activity via ERbeta from the hRARalpha
      1 promoter in Hep G2 cells required the amino-terminal region of ERbeta, a region
      that was not necessary for estrogen-induced ERbeta activity from an ERE in Hep G2
      cells. Additionally, the progesterone receptor (PR) antagonist RU486 acted as a
      weak (IC50 >1 microM) antagonist via hERalpha and as a fairly potent (IC50
      approximately 200 nM) antagonist via hERbeta from an ERE-driven reporter in cells
      that do not express PR. Although RU486 bound only weakly to ERalpha or ERbeta in
      vitro, it did bind to ERbeta in whole-cell binding assays, and therefore, it is
      likely metabolized to an ERbeta-interacting compound in the cell. Interestingly,
      RU486 acted as an agonist through ERbeta to stimulate the hRARalpha-1 promoter in
      Hep G2 cells. These findings may have ramifications in breast cancer treatment
      regimens utilizing tamoxifen or other ER antagonists and may explain some of the
      known estrogenic or antiestrogenic biological actions of RU486.

PMID- 10077000
TI  - Transition from monomeric to homodimeric DNA binding by nuclear receptors:
      identification of RevErbAalpha determinants required for RORalpha homodimer
      complex formation.
AB  - Nuclear hormone receptors belong to a class of transcription factors that
      recognize specific DNA sequences either as monomers, homodimers, or heterodimers
      with the common partner retinoic X receptor. In vitro mutagenesis studies, as
      well as determination of the crystal structure of several complexes formed by the
      DNA-binding domain of receptors bound to their cognate response elements, have
      begun to explain the molecular basis for protein-DNA and protein-protein
      interactions essential for high-affinity and specific DNA binding by nuclear
      receptors. In this study, we have used the related orphan nuclear receptors,
      RORalpha and RevErbAalpha, to study the molecular determinants involved in the
      transition from monomeric to homodimeric modes of DNA binding by nuclear
      receptors. While both receptors bind DNA as monomers to a response element
      containing a core AGGTCA half-site preceded by a 5'-A/T-rich flanking sequence,
      RevErbAalpha also binds as a homodimer to an extended DR2 element. Gain-of
      function experiments using point mutations and subdomain swaps between RORalpha
      and RevErbAalpha identify four amino acids within RevErbAalpha sufficient to
      confer RORalpha with the ability to form cooperative homodimer complexes on an
      extended DR2. This study reveals how the transition from monomer to homodimer DNA
      binding by members of the nuclear receptor superfamily could be achieved from
      relatively few amino acid substitutions.

PMID- 10077001
TI  - Distinguishing androgen receptor agonists and antagonists: distinct mechanisms of
      activation by medroxyprogesterone acetate and dihydrotestosterone.
AB  - Natural and pharmacological androgen receptor (AR) ligands were tested for their
      ability to induce the AR NH2-terminal and carboxyl-terminal (N/C) interaction in
      a two-hybrid protein assay to determine whether N/C complex formation
      distinguishes in vivo AR agonists from antagonists. High-affinity agonists such
      as dihydrotestosterone, mibolerone, testosterone, and methyltrienolone at
      concentrations between 0.1 and 1 nM induce the N/C interaction more than 40-fold.
      The lower affinity anabolic steroids, oxandrolone and fluoxymesterone, require
      concentrations of 10-100 nM for up to 23-fold induction of the N/C interaction.
      However no N/C interaction was detected in the presence of the antagonists,
      hydroxyflutamide, cyproterone acetate, or RU56187, at concentrations up to 1
      microM, or with 1 microM estradiol, progesterone, or medroxyprogesterone acetate;
      each of these steroids at 1-500 nM inhibited the dihydrotestosterone-induced N/C
      interaction, with medroxyprogesterone acetate being the most effective. In
      transient and stable cotransfection assays using the mouse mammary tumor virus
      reporter vector, all ligands displayed concentration-dependent AR agonist
      activity that paralleled induction of the N/C interaction, with antagonists and
      weaker agonists failing to induce the N/C interaction. AR dimerization and DNA
      binding in mobility shift assays and AR stabilization reflected, but were not
      dependent on, the N/C interaction. The results indicate that the N/C interaction
      facilitates agonist potency at low physiological ligand concentrations as
      detected in transcription, dimerization/DNA binding, and stabilization assays.
      However the N/C interaction is not required for agonist activity at sufficiently
      high ligand concentrations, nor does its inhibition imply antagonist activity.

PMID- 10077002
TI  - Turning a negative into a positive: vitamin D receptor interactions with the
      avian parathyroid hormone response element.
AB  - 1 ,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] negatively regulates expression of the
      avian PTH (aPTH) gene transcript, and a vitamin D response element (VDRE) near
      the promoter of the aPTH gene had previously been identified. The present report
      assessed whether the negative activity imparted by the aPTH VDRE could be
      converted to a positive transcriptional response through selective mutations
      introduced into the element. The tested sequences were derived from individual
      and combined mutations to 2 bp in the 3'-half of the direct repeat element,
      GGGTCAggaGGGTGT. Cold competition experiments using mutant and wild-type
      oligonucleotides in the mobility shift assay revealed minor differences in the
      ability of any of these sequences to compete for binding to a heterodimer complex
      comprised of recombinant proteins. Ethylation interference footprint analysis for
      each of the mutants produced unique patterns over the 3'-half-sites that were
      distinct from the weak, wild-type footprint. Transcriptional outcomes evaluated
      from a chloramphenicol acetyltransferase reporter construct utilizing the aPTH
      promoter found that the individual T-->A mutant produced an attenuated negative
      transcriptional response while the G-->C mutant resulted in a reproducibly weak
      positive transcriptional outcome. The double mutant, however, yielded a 4-fold
      increase in transcription, similar to the 7-fold increase observed from an
      analogous construct using the human osteocalcin VDRE. UV light crosslinking to
      gapped oligonucleotides assessed the polarity of heterodimer binding to the wild
      type and double mutant sequences and was consistent with the vitamin D receptor
      preferentially binding to the 5'-half of both elements. Finally, DNA affinity
      chromatography was used to immobilize heterodimer complexes bound to the wild
      type and double mutant sequences as bait to identify proteins that may
      preferentially interact with these DNA-bound heterodimers. This analysis revealed
      the presence of a p160 protein that specifically interacted with the heterodimer
      bound to the wild-type VDRE, but was absent from complexes bound to response
      elements associated with positive transcriptional activity. Thus, the sequence of
      the individual VDRE appears to play an active role in dictating transcriptional
      responses that may be mediated by altering the ability of a vitamin D receptor
      heterodimer to interact with accessory factor proteins.

PMID- 10077003
TI  - Mitogen-activated protein kinase and protein kinase A signaling pathways
      stimulate cholecystokinin transcription via activation of cyclic adenosine 3',5'
      monophosphate response element-binding protein.
AB  - Cholecystokinin (CCK) is a potent neuropeptide expressed in the small intestine
      and in the central nervous system. We have examined the effect of basic
      fibroblast factor (bFGF) and forskolin on CCK gene transcription and depicted the
      signaling pathways that lead to promoter activation. bFGF and forskolin
      stimulated promoter activity via a cAMP response element (CRE)/12-O
      tetradecanoylphorbol-13-acetate response element (TRE) located 80 bp upstream
      from the transcription initiation site. In nuclear extracts from unstimulated as
      well as stimulated cells, only CRE-binding protein (CREB) and activating
      transcription factor-1 (ATF-1) bound to the CRE/TRE, and activation was
      associated with phosphorylation of CREB serine-133 and ATF-1 serine-63. In murine
      F9 cells, CREB stimulated promoter activity 10-fold in the presence of protein
      kinase A (PKA), and in SK-N-MC cells activation was inhibited 60-70% by a
      dominant negative CREB mutant. In contrast, ATF-1 had no effect in F9 cells and
      exhibited a dominant negative effect in SK-N-MC cells. bFGF stimulation led to
      phosphorylation of the p38 mitogen-activated protein kinase (MAPK), and the
      extracellular signal-regulated kinase (ERK) MAPK and promoter activation,
      phosphorylation of CREB, and GAL4-CREB-dependent transcription were selectively
      prevented by a dominant negative Ras-mutant, the p38 MAPK-specific inhibitor
      SB203580, and the MAP/ERK kinase 1 (MEK1) inhibitor PD098059. Forskolin
      stimulation proceeded via the PKA pathway, and to a minor extent via the p38 and
      ERK MAPK pathways. We conclude that bFGF and forskolin stimulate the CCK gene
      promoter via the CRE/TRE(-80) in the proximal promoter region. Signaling proceeds
      through the p38 MAPK, the ERK MAPK, and the PKA-signaling pathways, which leads
      to cumulative phosphorylation and activation of CREB. We propose that bFGF in
      combination with neurotransmitters/neuropeptides coupling to the PKA-signaling
      pathway play an important role in the control of CCK gene expression.

PMID- 10077004
TI  - Defective retinoic acid regulation of the Pit-1 gene enhancer: a novel mechanism
      of combined pituitary hormone deficiency.
AB  - Pit-1 is a pituitary-specific transcription factor responsible for pituitary
      development and hormone expression in mammals. Pit-1 contains two protein
      domains, termed POU-specific and POU-homeo, which are both necessary for DNA
      binding and activation of the GH and PRL genes and regulation of the PRL, TSH
      beta subunit (TSH-beta), and Pit-1 genes. Pit-1 is also necessary for retinoic
      acid induction of its own gene during development through a Pit-1-dependent
      enhancer. Combined pituitary hormone deficiency is caused by defective
      transactivation of target genes in the anterior pituitary. In the present report,
      we provide in vivo evidence that retinoic acid induction of the Pit-1 gene can be
      impaired by a Pit-1 gene mutation, suggesting a new molecular mechanism for
      combined pituitary hormone deficiency in man.

PMID- 10077005
TI  - Human insulin receptor substrate-2 (IRS-2) is a primary progesterone response
      gene.
AB  - Elevated cAMP has been shown to unmask agonist activity of
      antiprogestin/antiglucocorticoid RU486. In our search for cellular target genes
      induced through this cross-talk mechanism, we identified human insulin receptor
      substrate-2 (IRS-2), a cytoplasmic signaling molecule that mediates effects of
      insulin, insulin-like growth factor-1 (IGF-I), and other cytokines by acting as a
      molecular adaptor between diverse receptor tyrosine kinases and downstream
      effectors. Our analysis of the regulation of IRS-2 in HeLa cell models shows that
      synergistic induction of IRS-2 by cAMP and RU486 can be mediated by progesterone
      receptors (PR) and glucocorticoid receptors (GR) and occurs through a relative
      slow mechanism that requires ongoing protein synthesis. Importantly, we
      demonstrate that IRS-2 mRNA is also inducible by progesterone, while
      glucocorticoid effects are only observed in the presence of cAMP. Up-regulation
      of IRS-2 by progesterone depends strictly on the presence of PR and occurs
      through a rapid mechanism, suggesting that it represents a primary
      transcriptional response. Furthermore, we show that expression of IRS-1, which
      also binds to receptors of insulin, IGF-I, and cytokines, is unaffected by
      progesterone. Thus, our results demonstrate that progesterone alters the ratio of
      IRS-1 and IRS-2 in PR-positive cells and implicate a mechanism through which
      progesterone can modulate the effects of insulin, IGF-I, and cytokines on cell
      proliferation, differentiation, and homeostasis.

PMID- 10077006
TI  - Transcriptional and posttranscriptional regulation of insulin-like growth factor
      binding protein-3 by cyclic adenosine 3',5'-monophosphate: messenger RNA
      stabilization is accompanied by decreased binding of a 42-kDa protein to a
      uridine-rich domain in the 3'-untranslated region.
AB  - The Madin Darby bovine kidney (MDBK) cell line was used to investigate the
      mechanisms underlying the cAMP regulation of insulin-like growth factor binding
      protein-3 (IGFBP-3) gene expression. Treatment of confluent monolayers either
      with forskolin or cAMP produced a 60- to 75-fold induction of IGFBP-3 mRNA and
      protein levels. This effect did not require new protein synthesis as inhibition
      of translation by cycloheximide actually caused a 2-fold increase in the cAMP
      induction. The rates of IGFBP-3 gene transcription, assessed by nuclear run-on
      assays, increased approximately 15-fold in cells exposed to cAMP. In addition,
      the half-life of the IGFBP-3 mRNA transcript was increased approximately 3-fold
      in the presence of cAMP. Gel mobility shift and competition experiments revealed
      the specific binding of an approximately 42-kDa cytoplasmic protein factor to the
      3'-untranslated region (3'-UTR) of the IGFBP-3 mRNA. A 21-nucleotide uridine-rich
      segment that contained no AUUUA motif was sufficient for the specific binding.
      The binding activity of this protein was reduced after cAMP treatment but was
      increased by phosphatase treatment. In conclusion, the cAMP induction of IGFBP-3
      mRNA in MDBK cells occurred at both the transcriptional and posttranscriptional
      levels. The IGFBP-3 mRNA stabilization in MDBK cells probably involved the
      phosphorylation of a member of the family of U-rich region mRNA-binding proteins
      and is the first reported member whose RNA-binding activity is reduced by cAMP.

PMID- 10077007
TI  - Action of insulin receptor substrate-3 (IRS-3) and IRS-4 to stimulate
      translocation of GLUT4 in rat adipose cells.
AB  - The insulin receptor initiates insulin action by phosphorylating multiple
      intracellular substrates. Previously, we have demonstrated that insulin receptor
      substrates (IRS)-1 and -2 can mediate insulin's action to promote translocation
      of GLUT4 glucose transporters to the cell surface in rat adipose cells. Although
      IRS-1, -2, and -4 are similar in overall structure, IRS-3 is approximately 50%
      shorter and differs with respect to sites of tyrosine phosphorylation.
      Nevertheless, as demonstrated in this study, both IRS-3 and IRS-4 can also
      stimulate translocation of GLUT4. Rat adipose cells were cotransfected with
      expression vectors for hemagglutinin (HA) epitope-tagged GLUT4 (GLUT4-HA) and
      human IRS-1, murine IRS-3, or human IRS-4. Overexpression of IRS-1 led to a 2
      fold increase in cell surface GLUT4-HA in cells incubated in the absence of
      insulin; overexpression of either IRS-3 or IRS-4 elicited a larger increase in
      cell surface GLUT4-HA. Indeed, the effect of IRS-3 in the absence of insulin was
      approximately 40% greater than the effect of a maximally stimulating
      concentration of insulin in cells not overexpressing IRS proteins. Because
      phosphatidylinositol (PI) 3-kinase is essential for insulin-stimulated
      translocation of GLUT4, we also studied a mutant IRS-3 molecule (IRS-3-F4) in
      which Phe was substituted for Tyr in all four YXXM motifs (the phosphorylation
      sites predicted to bind to and activate PI 3-kinase). Interestingly,
      overexpression of IRS-3-F4 did not promote translocation of GLUT4-HA, but
      actually inhibited the ability of insulin to stimulate translocation of GLUT4-HA
      to the cell surface. Our data suggest that IRS-3 and IRS-4 are capable of
      mediating PI 3-kinase-dependent metabolic actions of insulin in adipose cells,
      and that IRS proteins play a physiological role in mediating translocation of
      GLUT4.

PMID- 10077008
TI  - Magnetic resonance cholangiopancreatography.
AB  - Magnetic resonance cholangiopancreatography (MRCP) uses MR imaging to visualize
      fluid in the biliary and pancreatic ducts as high signal intensity on T2-weighted
      sequences; it is the newest modality for biliary and pancreatic duct imaging.
      MRCP is of proven utility in a variety of biliary and pancreatic diseases,
      including choledocholithiasis, congenital anatomic variants, chronic
      pancreatitis, post-cholecystectomy disorders, and neoplastic duct obstruction.
      MRCP is an evolving technique, but it has reached the stage of development where
      it is clinically useful and of comparable accuracy to conventional
      cholangiography. With further progress, it is likely that by the start of the new
      millennium MRCP will replace diagnostic endoscopic retrograde
      cholangiopancreatography as the modality of choice for imaging the biliary and
      pancreatic ducts.

PMID- 10077009
TI  - Accuracy of T1 measurement in dynamic contrast-enhanced breast MRI using two- and
      three-dimensional variable flip angle fast low-angle shot.
AB  - In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues,
      are typically performed as a first step in implementing compartmental analysis of
      contrast-enhanced breast magnetic resonance imaging (MRI) data. We have extended
      previously described methodology for in vivo T1 measurement (using a variable
      flip-angle gradient-recalled echo technique) to two-dimensional (2D), fast low
      angle shot (FLASH). This approach requires computational modeling of slice
      selective radiofrequency (RF) excitation to correct for nonrectangular slice
      profiles. The accuracy with which breast tissue T1 values can be measured by this
      approach is examined: T1 measurements from phantom and in vivo image data
      acquired with 2D and 3D FLASH imaging sequences are presented. Significant
      sources of error due to imaging pulse sequence quality and RF transmit field
      nonuniformity in the breast coil device that will have detrimental consequences
      for compartmental analysis are identified. Rigorous quality assurance programs
      with calibrated phantoms are thus recommended, to verify the accuracy with which
      T1 measurements are obtained.

PMID- 10077010
TI  - Differentiation between the effects of T1 and T2* shortening in contrast-enhanced
      MRI of the breast.
AB  - The purpose of this study is to describe a technique for magnetic resonance
      imaging (MRI) that can potentially improve identification of malignant tissue in
      the human breast. The suggested MRI technique is based on the differentiation
      between two competing effects leading to opposite changes in image intensity,
      namely, T1 and T2* shortening caused by administration of gadolinium chelate. The
      proposed approach also allows calculation of changes in the R2* relaxation rate
      in breast tissue. The feasibility of the technique for in vivo MRI and increased
      lesion contrast is demonstrated. The results indicate that this technique may
      improve detection of malignant breast tissue.

PMID- 10077011
TI  - Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast
      tumors in rats by using three MR contrast agents.
AB  - A carcinogen (N-ethyl-N-nitrosourea)-induced animal tumor model was established
      to grow malignant and benign breast tumors. In each tumor the pharmacokinetic
      characteristics were measured by using three contrast agents, gadolinium
      diethylene-triamine-pentaacetic acid (Gd-DTPA; <1 kD), Gadomer-17 (35 kD), and
      albumin-Gd-DTPA (70-90 kD). Infiltrating ductal carcinomas (IDC) with low,
      medium, and high Scarf-Bloom-Richardson grades and fibroadenomas (FA) were
      analyzed. We found that Gd-DTPA could differentiate between FA and malignant
      tumors, but not between malignant tumors of low and high grades. In contrast, the
      intermediate size agent Gadomer-17 could differentiate between high-grade and low
      grade IDC, but not between low-grade IDC and FA due to their similar enhancement
      patterns (despite their different origins). The largest agent, albumin-Gd-DTPA,
      was capable of differentiating both, but the low contrast-to-noise ratio was its
      major technical concern. The results in this breast tumor model suggest that
      macromolecular agents provide useful information for differential diagnosis among
      IDCs of various grades, but they do not provide superior information than Gd-DTPA
      for differential diagnosis between IDC and FA.

PMID- 10077012
TI  - Do T2-weighted pulse sequences help with the differential diagnosis of enhancing
      lesions in dynamic breast MRI?
AB  - In this study, our purpose was to determine whether T2-weighted images are a
      useful diagnostic adjunct for lesion characterization in dynamic breast MRI. On a
      1.5-T system, 205 enhancing benign and malignant breast tumors were examined. The
      standardized protocol consisted of a T2-weighted turbo spin echo (TSE) pulse
      sequence with and without spectral fat suppression (SPIR), followed by a two
      dimensional dynamic series with subtraction postprocessing. In 59 cases, T2*
      weighted gradient-echo images also were obtained. Two independent radiologists
      visually rated the lesions (101 malignant, 104 benign) as having either a low or
      a high signal with respect to the adjacent glandular tissue. To assess age
      dependency of lesion enhancement velocities and T2-TSE signal intensities, we
      compared the results for patients at or below the age of 50 (group A), between 40
      and 50 (group B), and beyond the age of 50 (group C). In T2-weighted TSE images,
      breast cancers were iso- or hypointense with respect to breast parenchyma in 87%
      of cases, whereas fibroadenomas were hyperintense in 71%. Visual assessment of
      lesion appearance in T2-weighted TSE images allowed to distinguish between
      fibroadenomas and breast cancers, with a respective sensitivity, specificity,
      positive predictive value, and negative predictive value of 72%, 75%, 46%, and
      90% for young patients; 94%, 66%, 78%, and 89% for the patients between 40 and
      50; and 89%, 62%, 85%, and 68% for the patients over 50 years of age. No
      significant difference was found for the distribution of signal intensities of
      lesions in T2*-weighted images or in fat-suppressed images. In a contrast
      enhancing breast lesion, careful analysis of T2-weighted TSE images can improve
      differential diagnosis. The accuracy of this criterion varies with age.

PMID- 10077013
TI  - Quantification of myocardial perfusion with FAST sequence and Gd bolus in
      patients with normal cardiac function.
AB  - The present study reports on a new calibration of the magnetic resonance imaging
      (MRI) signal intensity of a fast gradient-echo sequence used for in vivo
      myocardial perfusion quantification in patients. The signal from a FAST sequence
      preceded by a arrhythmia-insensitive magnetization preparation was calibrated in
      vitro using tubes filled with various gadolinium (Gd) solutions. Single short
      axis views of the heart were obtained in patients (n = 10) with normal cardiac
      function. Myocardial and blood signal intensity were converted to concentration
      of Gd according to the in vitro calibration curve and fitted by a one-compartment
      model. K1 [first-order transfer constant from the blood to the myocardium for the
      gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA)] and Vd (distribution
      volume of Gd-DTPA in myocardium) obtained from the fit of the MRI-derived
      perfusion curves were 0.72+/-0.22 (mL/min/g) and 15.3+/-5.22%. These results were
      in agreement with previous observations on animals and demonstrated that a
      reliable measurement of myocardial perfusion can be obtained by MRI in patients
      with an in vitro calibration procedure.

PMID- 10077014
TI  - MRI of acute myocardial ischemia: comparing a new contrast agent, Gd-DTPA-24
      cascade-polymer, with Gd-DTPA.
AB  - A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic
      acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent
      delineation of acute myocardial ischemia. Acute myocardial ischemia was produced
      in 12 rats by occluding the anterior branch of the left coronary artery for 20-40
      minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30
      minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using
      equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal
      intensity (deltaSI) in normal and ischemic myocardium were observed. In normal
      myocardium, both contrast agents caused a sharp increase in deltaSI, followed by
      a decline to baseline values over the 30-minute period. Enhancement in the
      ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic
      myocardium than the cascade polymer, which gave rise to virtually no enhancement.
      Significant differences (P<0.05) in signal enhancement between normal and
      ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes
      with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal
      window of dynamic contrast-enhanced MRI for the differentiation of ischemic and
      normal myocardium. Identification of the ischemic zone is easier with the cascade
      polymer, which demonstrates virtually no signal enhancement in this territory.

PMID- 10077015
TI  - Detection of acute myocardial ischemia using first-pass dynamics of MnDPDP on
      inversion recovery echoplanar imaging.
AB  - Previous studies used manganese N,N'-bis-(pyridoxal 5-phosphate)ethylenediamine
      N,N'-diacetic acid (MnDPDP) to detect myocardial ischemia at a dose of 0.4
      mmol/kg with spin echo imaging. The purpose of this study was to detect acute
      myocardial ischemia using MnDPDP at a dose range near that approved for
      hepatobiliary imaging (0.005 mmol/kg) in conjunction with inversion recovery
      echoplanar imaging (IR EPI). Regional ischemia was produced in 26 rats by
      occluding the left coronary artery for 20-30 minutes before imaging. Consecutive
      32 IR EP images (inversion time [TI]/TR/TE 700/2000/10 msec) were obtained to
      monitor the first pass of MnDPDP at four incremental doses (0.005, 0.01, 0.02, or
      0.04 mmol/kg, n = 6-8). MnDPDP produced dose-dependent enhancement of left
      ventricular blood and normal myocardium, but not ischemic myocardium.
      Quantitative analysis revealed a difference in signal intensities (P<0.05)
      between normal and ischemic myocardium at the time of peak enhancement in all
      groups. However, differential enhancement between normal and ischemic myocardium
      produced clear visual delineation of the ischemic region only at doses > or =0.01
      mmol/kg. In conclusion, acute myocardial ischemia can be detected with IR EPI
      using doses close to the clinically approved dose of MnDPDP.

PMID- 10077016
TI  - The contributory role of interstitial water in Gd-DTPA-enhanced MRI in myocardial
      infarction.
AB  - We studied the mechanism underlying regional enhancement of myocardial infarction
      using T1-weighted MRI with gadolinium (Gd)-DTPA. Anterior myocardial infarction
      (MI) was produced by left anterior descending coronary artery ligation in three
      groups of rats as follows: 60 minutes occlusion (occlusion group, N = 6), 60
      minutes occlusion plus 120 minutes reperfusion (reperfusion group, N = 8), and
      sham-operated (control, N = 6). In Gd-DTPA-enhanced MRI, MI was demarcated as a
      hypoenhanced region in the occlusion group and as a homogeneous hyperenhanced
      region in the reperfusion group. Both Gd-DTPA tissue concentration and tissue
      water content in the anterior wall were highest in the reperfusion group
      (P<0.05), a finding suggestive of microscopically observed interstitial edema.
      The data suggest that regional accumulation of Gd-DTPA in the reperfused group
      can be explained by increased interstitial water content, contributing to the
      delayed washout of the water-soluble contrast medium.

PMID- 10077017
TI  - Safety and preliminary findings with the intravascular contrast agent NC100150
      injection for MR coronary angiography.
AB  - In this Phase I clinical study, a novel ultrasmall superparamagnetic iron oxide
      contrast agent, NC100150 Injection (Nycomed Imaging, Oslo, Norway, a part of
      Nycomed Amersham), was used in two-dimensional magnetic resonance coronary
      angiography (MRCA). Safety and imaging data were acquired from 18 healthy male
      volunteers at both 0.5 and 1.5 T, before and after the administration of NC100150
      Injection. Through-plane and in-plane images of the right coronary artery were
      analyzed. The postcontrast imaging sequences used prepulses and a high flip
      angle, to introduce T1 weighting. At 1.5 T (TE 2.6 msec), the through-plane
      coronary artery signal-to-noise ratio (SNR) (P = 0.04), coronary artery-to-fat
      signal difference-to-noise ratio (SDNR) (P = 0.001), coronary artery-to
      myocardium SDNR (P<0.001), and coronary artery delineation (P<0.001) were
      improved by the administration of NC100150 Injection. For in-plane imaging,
      coronary artery delineation improved, but there were no significant changes in
      the SNR and SDNR. At 0.5 T, with the longer TE (6.7 msec) imaging sequence used,
      there was a reduction in the SNR (P = 0.01), the fat SDNR (through-plane P =
      0.02; in-plane P = 0.25), and the coronary artery diameter (P<0.01 in both
      imaging planes). There was a trend toward improvement in the myocardial SDNR and
      coronary artery delineation. In conclusion, NC 100150 Injection was given safely
      to 18 healthy subjects, with no major adverse reactions. Coronary artery
      delineation was improved in both imaging planes at 1.5 T, with a trend toward
      improvement at 0.5 T. At 1.5 T, with a short TE imaging sequence, the marked T1
      shortening effects of NC100150 Injection were dominant, leading to an improvement
      in the quantitative parameters for the through-plane images. At 0.5 T, with a
      longer TE imaging sequence, the T2* effects of the contrast agent played a role
      in reducing the quantitative image parameters. With further optimization of
      imaging sequences, to take advantage of the long-lived intravascular T1
      shortening effect of NC100150 Injection, further improvements in MRCA will be
      possible.

PMID- 10077018
TI  - Improved delineation of human brain tumors on MR images using a long-circulating,
      superparamagnetic iron oxide agent.
AB  - The purpose of this study was to corroborate experimental findings that long
      circulating, superparamagnetic iron oxide contrast agents accumulate at the
      margins of human brain tumors, thereby improving their delineation on magnetic
      resonance (MR) images. This limited clinical study examined a total of four
      patients with brain tumors (three with primary gliomas and one with metastatic
      melanoma; n = 8 lesions) who were given a pharmaceutical formulation of a
      superparamagnetic, ultra-small-particulate iron oxide (USPIO, intravenous dose of
      1.1 mg Fe/kg). The agent has a characteristically long plasma half-life and is
      currently undergoing Phase III clinical trials for liver disease (AMI-227,
      Advanced Magnetics, Cambridge, MA). MR (conventional spin-echo and gradient-echo)
      images of the brain were obtained before and 12, 24, and/or 36 hours after
      administration of the agent, with follow-up several weeks later. Twelve to 36
      hours after IV administration of the USPIO, both primary and metastatic brain
      tumors showed readily detectable increases in signal intensity on T1-weighted
      spin-echo images. Unlike the pattern of enhancement with a gadolinium (Gd)
      chelate, which occurred immediately and decreased within hours, that with the
      USPIO occurred gradually, with a peak at 24 hours, and decreased over several
      days. Whereas the enhancing tumor margin with the Gd chelate blurred with time
      due to diffusion of the agent, the margin with the USPIO remained sharp,
      presumably due to the much lower diffusion coefficient (large size) of the
      particles and partly because of local endocytosis by tumor cells. Compared with
      Gd chelates, long-circulating, superparamagnetic iron oxide contrast agents can
      provide prolonged delineation of the margins of human brain tumors on MR images,
      which has implications for the targeting of diagnostic biopsies and the planning
      of surgical resections.

PMID- 10077019
TI  - Optimization of fast acquisition methods for whole-brain relative cerebral blood
      volume (rCBV) mapping with susceptibility contrast agents.
AB  - Fast gradient-echo magnetic resonance scan techniques with spiral and rectilinear
      (echoplanar) k-space trajectories were optimized to perform bolus-tracking
      studies of human brain. Cerebral hemodynamics were studied with full brain
      coverage, a spatial resolution of 4 mm, and a temporal resolution of 2 seconds.
      The sensitivity of the techniques to detect image signal-intensity changes during
      the first pass of the contrast agent was studied at a range of TEs using
      dedicated experiments. For single-shot versions of spiral scanning and echoplanar
      imaging techniques with a 0.1-mmol/kg injection of gadolinium diethylenetriamine
      pentaacetic acid using a mechanical injector at 10 mL/sec under 1.5 T, the
      maximum sensitivity was obtained at TEs between 35 and 45 msec. At TEs less than
      35 msec, signal-intensity artifacts were observed in the images. Analysis of the
      point-spread function revealed that susceptibility changes induced by the
      contrast agent can result in signal shifts to neighboring voxels. These artifacts
      are attributed to susceptibility-related signal changes during the acquisition
      window.

PMID- 10077020
TI  - A multicenter, randomized, double-blind study to evaluate the safety,
      tolerability, and efficacy of OptiMARK (gadoversetamide injection) compared with
      Magnevist (gadopentetate dimeglumine) in patients with liver pathology: results
      of a Phase III clinical trial.
AB  - The purpose of this study was to evaluate the safety and efficacy of OptiMARK
      (gadoversetamide injection) compared with Magnevist (gadopentetate dimeglumine)
      in hepatic MRI of patients with suspected liver pathology. A Phase III,
      multicenter, randomized, double-blind, parallel group study was performed in
      adults with suspected liver pathology. All patients underwent contrast-enhanced
      computed tomography within 3 weeks prior to magnetic resonance scanning. Ninety
      nine patients received OptiMARK, and 94 patients received Magnevist at a dose of
      0.1 mmol/kg. Precontrast T1- and T2-weighted spin-echo imaging and T1-weighted
      gradient-echo imaging were performed, followed by T1-weighted gradient-echo
      imaging at 15-20 seconds, 1 minute, and 5 minutes after intravenous contrast
      injection. Three primary efficacy endpoints (confidence in lesion diagnosis,
      level of conspicuity, and lesion border delineation) were evaluated on the
      precontrast image set and compared with the pre plus postcontrast image set.
      Vital signs, physical examination, electrocardiograms (ECGs), and laboratory
      parameters (chemistry, hematology, and urinalysis) were measured at various time
      points. Adverse events were recorded. The study design and statistical analyses
      were chosen to demonstrate presumed equivalence of OptiMARK and Magnevist. There
      were no statistically significant differences in efficacy between OptiMARK and
      Magnevist as assessed by either blinded readers or the on-site principal
      investigators. No serious or unexpected adverse events were noted. Of the 193
      patients receiving contrast media, 82 experienced a total of 154 adverse events.
      Thirty-three (21.4%) of these 154 adverse events were felt by the on-site
      investigators to be probably related to either study agent: 15 events in 9
      patients in the OptiMARK group, and 18 events in 13 patients in the Magnevist
      group. Headache was the most common adverse event, occurring in 10.1% of the
      OptiMARK patients and 12.8% of the Magnevist patients. No clinically relevant
      trends were observed in any laboratory parameter or ECG findings in either
      treatment group. The results demonstrate the safety, efficacy, and equivalence of
      OptiMARK and Magnevist at a dose of 0.1 mmol/kg in hepatic magnetic resonance
      imaging of patients with suspected liver pathology.

PMID- 10077021
TI  - Enhanced tumor detection in the presence of liver cirrhosis: experimental study
      on the diagnostic value of a superparamagnetic iron oxide MR imaging contrast
      agent (NSR 0430).
AB  - The purpose of this study was to determine the diagnostic value of the
      superparamagnetic iron oxide NSR 0430 for the detection of focal liver lesions in
      the presence of advanced cirrhosis. Cirrhosis and growth of cholangiofibromas
      were induced in 22 rats by administration of thioacetamide. Sixteen non-cirrhotic
      animals served as controls. T1 and T2 relaxation times of liver and tumor tissue
      of 12 animals were measured spectroscopically. In 10 animals in vivo MRI was
      performed before and 1 hour after contrast administration, and then the tumor-to
      liver contrast-to-noise ratio (CNR) was calculated. All specimens were evaluated
      histologically. After contrast administration, T1 and T2 values of liver tissue
      showed a significant decrease of 18% (P = 0.01) and 31% (P = 0.009),
      respectively, whereas relaxation times of tumor tissue did not change. On
      precontrast turbo spin-echo images, 40 tumors could be identified; after contrast
      administration, 95 lesions were visible. CNR increased significantly after
      contrast administration by 297% at a TE of 50 msec and by 254% at a TE of 90
      msec. In conclusion, our in vitro and in vivo results demonstrate that
      administration of NSR 0430 substantially improves liver-to-tumor CNR and lesion
      detection on T2-weighted magnetic resonance images even in the presence of severe
      cirrhosis.

PMID- 10077022
TI  - Evaluation of liver diseases via MTC and contrast agent.
AB  - Our goal was to characterize pathological tissues of liver by magnetic resonance
      (MR)-related parameters such as T1 and magnetization transfer (MT) indices and to
      evaluate the clinical efficacy of MT contrast (C) in diagnosis of liver diseases
      via binomial pulsed saturation, with and without the administration of the
      paramagnetic agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA).
      Fifty-one cases of liver disorders were included in this study. Among the more
      important findings were the following: a) cirrhotic livers have significantly
      higher MT indices than normal liver, while hepatoma, metastatic tumor and fatty
      liver have sub-normal MT indices; b) in general, although with notable
      exceptions, images with MT give significantly better contrast indices than
      control images; and c) MT with Gd-DTPA rarely fares any better than the MT
      technique alone, although again with notable exceptions. MTC is a potentially
      powerful technique for diagnosing liver diseases, provided it can be optimally
      exploited for each individual disease type.

PMID- 10077023
TI  - A retrospective analysis of the accuracy of T2-weighted images and dynamic
      gadolinium-enhanced sequences in the detection and characterization of focal
      hepatic lesions.
AB  - The aim of this study was to determine the relative ability of T2-weighted and
      dynamic gadolinium-enhanced T1-weighted gradient-echo sequences to detect and
      characterize focal hepatic lesions. We retrospectively studied 37 patients with
      proven focal hepatic lesions using the following sequences: a T1-weighted spin
      echo sequence (T1), a T2-weighted sequence (T2), and a series of breath-hold
      dynamic gadolinium-enhanced T1-weighted gradient-echo sequences (Gd). Two
      observers were asked to determine retrospectively the number and type of focal
      hepatic lesions present using images from three combinations of sequences (T1+T2,
      T1+Gd, T1+T2+Gd). Proof of the number and diagnosis of focal lesions in each
      patient was established using a consensus read. Both readers detected more focal
      lesions when both the T2-weighted sequences and the gadolinium-enhanced sequences
      were available than on either sequence alone, although this improvement reached
      statistical significance (P<0.05) only for one of the readers. There was no
      significant difference (P<0.05) in the ability to characterize lesions between
      any of the sets of sequences. The combination of dynamic gadolinium-enhanced
      images and T2-weighted images was shown to assess focal hepatic lesions better
      than either of these sequences alone.

PMID- 10077024
TI  - Detection of hepatocellular carcinoma: comparison of T2-weighted breath-hold fast
      spin-echo sequences and high-resolution dynamic MR imaging with a phased-array
      body coil.
AB  - The purpose of our study was to compare T2-weighted breath-hold fast spin-echo
      sequence (BHFSE) and high-resolution dynamic MR imaging (HR-DMRI) in the
      detection of hepatocellular carcinoma (HCC). Short and long T2-weighted BHFSE
      sequences and biphasic HR-DMRI including arterial-dominant and delayed phase
      images with a phased-array body coil were performed in 30 consecutive patients
      with 37 HCCs. The lesion-to-liver contrast-to-noise ratio (CNR) was
      quantitatively measured. The lesion conspicuity and delineation was qualitatively
      rated according to a four-point scale. The lesion-to-liver CNR was highest with
      the arterial-dominant phase HR-DMRI and was significantly higher than those
      obtained with both short and long T2-weighted BHFSE and those obtained with
      unenhanced and delayed HR-DMRI. The CNR obtained with short T2-weighted BHFSE was
      significantly higher than those obtained with long T2-weighted BHFSE and with
      unenhanced and delayed HR-DMRI. The sensitivity for the sequences was 78.4%
      (29/37) for short T2-weighted BHFSE, 67.6% (25/37) for long T2-weighted BHFSE,
      37.8% (14/37) for unenhanced HR-DMRI, 97.3% (36/37) for arterial-dominant phase
      HR-DMRI, and 43.2% (16/37) for delayed HR-DMRI. The sensitivity of serial dynamic
      MR imaging combined with unenhanced, arterial-dominant phase imaging and delayed
      phase imaging was 100% (37/37). The score in the qualitative analysis of the
      lesion conspicuity and delineation was highest for the arterial-dominant phase HR
      DMRI and was significantly higher than that for the short T2-weighted BHFSE. The
      score for the short T2-weighted BHFSE was significantly higher than that for the
      long T2-weighted BHFSE and that for the unenhanced HR-DMRI. Arterial-dominant
      phase HR-DMRI is superior to the T2-weighted BHFSE technique, and also HR-DMRI
      combined with unenhanced, arterial-dominant and delayed phases is the most
      sensitive technique in the detection of HCC.

PMID- 10077025
TI  - Sequence optimization in mangafodipir trisodium-enhanced liver and pancreas MRI.
AB  - To find an optimal magnetic resonance (MR) sequence for mangafodipir trisodium
      enhanced liver and pancreas imaging, six healthy volunteers were studied using a
      1.5 T MR system with different T1-weighted abdominal imaging sequences. These
      were turbo field (gradient)-echo (TFE), fast field (gradient)-echo (FFE), and
      spin-echo sequences before and after mangafodipir trisodium administration.
      Various parameter combinations were investigated within each sequence type, and
      then the best combination was found and compared with those of the other
      sequences. Signal intensity (SI) measurements were made in regions of interest in
      the liver, pancreas, and a reference marker with a known T1 value. Contrast index
      (CI, SItissue/SImarker) and contrast-to-noise ratio (CNR,
      [SItissue/SImarker]/SDbackground) were calculated, and percentage CI increase and
      CNR in the postcontrast images were used for the best sequence evaluation.
      Regarding CI, the TFE sequence with a TR/TE/flip angle of 15 msec/4.6 msec/20
      degrees and inversion time of 300 msec had the largest pre- to postcontrast
      percentage increase. The FFE sequence with a TR/TE/flip angle of 140 msec/4.6
      msec/90 degrees had the highest postcontrast CNR and is considered to be the
      optimal sequence for mangafodipir trisodium-enhanced MR imaging of the liver and
      pancreas.

PMID- 10077026
TI  - Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial
      gadolinium-enhanced gradient-echo images.
AB  - The purpose of this study was to determine the magnetic resonance imaging (MRI)
      features of pyogenic hepatic abscesses on T1-weighted, T2-weighted, and serial
      gadolinium (Gd)-enhanced T1-weighted spoiled gradient-echo (SGE) images including
      images acquired in the immediate, intermediate, and late phases of enhancement.
      The MRI studies of 20 patients with pyogenic liver abscesses were retrospectively
      reviewed. All patients were examined on 1.5 (n = 19) and 1.0 (n = 1) T MR
      scanners. MR studies included T1-weighted, T2-weighted, and serial Gd-enhanced
      SGE images. The following determinations were made: signal intensity of the
      abscess cavity and perilesional liver tissue, and the presence of internal
      septations, layering material, or air in the abscess cavity. The pattern of
      enhancement of the abscess wall, internal septae and peri-abscess liver were
      evaluated on serial Gd-enhanced SGE images. A total of 53 abscesses were observed
      in the 20 patients. Fortyeight abscesses were hypointense on T1-weighted and
      hyperintense on T2-weighted images. Internal septations were present in four
      abscesses. Lower signal intensity material was observed in a dependent location
      on T2-weighted images in one abscess. Signal void foci of air located on the
      nondependent surface was observed in two abscesses. Two other abscesses contained
      signal void air that occupied the entire abscess cavity, observed on all imaging
      sequences. On serial gadolinium-enhanced images, all abscesses revealed early
      enhancement of the wall, which persisted with negligible change in degree of
      enhancement or thickness on delayed images. Abscess walls ranged in thickness
      from 2 to 5 mm. Internal septations ranged in thickness from 2 to 3 mm. Abscess
      walls and septations were relatively uniform in thickness with no evidence of
      focal nodularity. Periabscess liver tissue was mildly hypointense on T1-weighted
      and mildly hyperintense on T2-weighted images in 20 lesions, which were either
      circumferential (n = 12) or wedge-shaped (n = 8). All these regions enhanced more
      than the remainder of the liver on immediate post-gadolinium images and remained
      relatively hyperintense on late phase images. Periabscess liver parenchyma was
      isointense on both T1- and T2-weighted images in 18 lesions, and in these lesions
      wedge-shaped subsegmental (n = 6) or segmental (n = 12) enhancement was observed
      on immediate gadolinium-enhanced images, which faded to isointensity on
      intermediate phase images. No perilesional signal changes and enhancement
      difference was observed in 15 lesions. Characteristic features of abscesses
      include: intense mural enhancement on early gadolinium-enhanced images, which
      persists with negligible change in thickness and intensity on later post
      gadolinium images, and the presence of periabscess increased enhancement on
      immediate post-gadolinium images. These MRI features may help to distinguish
      abscesses from other focal liver lesions during differential diagnosis.

PMID- 10077027
TI  - Safety profile of ultrasmall superparamagnetic iron oxide ferumoxtran-10: phase
      II clinical trial data.
AB  - The safety data from the phase II clinical trial of ferumoxtran-10, an ultrasmall
      superparamagnetic iron oxide contrast agent, are presented. One hundred and four
      patients with focal liver or spleen pathologies underwent ferumoxtran-10-enhanced
      magnetic resonance (MR) imaging at doses of 0.8, 1.1, and 1.7 mg Fe/kg. Overall,
      15% patients reported a total of 33 adverse events, regardless of causality. The
      adverse events most frequently seen were dyspnea (3.8%), chest pain (2.9%), and
      rash (2.9%). No serious adverse events were reported during the 48 hour
      observation period. There were no clinically significant effects on vital signs,
      physical examination, and laboratory results. Ferumoxtran-10 is a safe and well
      tolerated MR contrast agent.

PMID- 10077028
TI  - Investigation of lanthanide-based starch particles as a model system for liver
      contrast agents.
AB  - Gadolinium and dysprosium diethylenetriamine pentaacetic acid-labeled starch
      microparticles (Gd-DTPA-SP and Dy-DTPA-SP) were investigated as model liver
      contrast agents. The liver contrast efficacy of particles with low and high metal
      contents was compared in two imaging models: in vivo rat liver and ex vivo
      perfused rat liver. The biodistribution of intravenously injected particles was
      also assessed by ex vivo relaxometry and inductively coupled plasma atomic
      emission spectrophotometry of tissues. All particles reduced the liver signal
      intensity on T2-weighted spin-echo and gradient-recalled echo images as a result
      of susceptibility effects. Because of their higher magnetic susceptibility, the
      Dy-DTPA-SP were more effective negative contrast enhancers than the Gd-DTPA-SP.
      On T1-weighted spin-echo images, only the Gd-DTPA-SP with low metal content
      significantly increased the liver signal intensity. In addition, these low
      loading Gd-DTPA-SP markedly reduced the blood T1. The two latter observations
      were not consistent with the anticipated blood circulation time of
      microparticles, but were a result of the lower stability of these particles in
      blood compared with Gd-DTPA-SP, which has a high metal content. Regardless of
      stability or imaging conditions, the paramagnetic starch particles investigated
      showed potential as negative liver contrast enhancers. However, the observed
      accumulation of particles in the lungs represented a biological limitation for
      their use as contrast agents.

PMID- 10077029
TI  - Diagnosis of adrenal adenoma: value of central spot of high-intensity
      hyperintense rim sign and homogeneous isointensity to liver on gadolinium
      enhanced fat-suppressed spin-echo MR images.
AB  - Eighty-nine patients with 108 adrenal masses, either adenomas (n = 88) or
      malignant lesions (n = 20), underwent magnetic resonance imaging (MRI) of the
      abdomen at 0.5 T for the purpose of determining whether adrenal adenomas could be
      differentiated from malignant lesions on gadolinium-enhanced fat-suppressed T1
      weighted spin-echo (SE) images (Gd-E FS T1WI) and on T2-weighted SE images. The
      imaging protocol included conventional unenhanced SE T1- and T2-weighted
      sequences and Gd-E FS T1WI. Three observers independently evaluated signal
      intensity on unenhanced and enhanced images and also the presence of structures
      of high signal intensity in the outer margin [hyperintense rim sign (HRS)] or in
      the center [hyperintense central spot (HCS)] of the adrenal masses. Forty-one
      (46.5%) of 88 adenomas were homogeneously isointense to liver in unenhanced and
      enhanced T1-weighted sequences and in T2WI. HCS and HRS were observed in 33/88
      (37.5%) and 15/88 (17%) adenomas, respectively, on Gd-E FS T1WI; in contrast,
      these signs were never revealed in any case of malignant lesions. Sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy in classifying lesions as suggestive of adenoma were 93%, 90%, 98%, 75%,
      and 93%, respectively. Visual evaluation of details of tumor structures on Gd-E
      FS T1WI allows good characterization of adrenal masses. HCS, HRS, and homogeneous
      isointensity to liver are characteristic signs of adrenal adenomas.

PMID- 10077030
TI  - Differentiation of prostatic carcinoma and benign prostatic hyperplasia:
      correlation between dynamic Gd-DTPA-enhanced MR imaging and histopathology.
AB  - One of the major factors limiting the staging accuracy of conventional magnetic
      resonance imaging (MRI) for prostatic carcinoma, is the similarity in signal
      intensity between tumor and coexisting benign prostatic hyperplasia (BPH). As
      neovascularity is an independent indicator of pathological state, dynamic
      contrast-enhanced MRI may yield additional information. This study correlates the
      histopathological findings from 12 radical prostatectomy patients on a region-by
      region basis, with pharmacokinetic modeling of dynamic contrast-enhanced (0.2
      mmol dimeglumine gadopentetate/kg), fast multiplanar spoilt gradient-recalled
      echo images, using a two-compartment simplex minimization technique. Quantitative
      analysis demonstrated differences in the amplitude of the initial contrast
      upslope and contrast exchange rate between tumor and fibromuscular BPH (P<0.03
      and P<0.03, respectively) and for the contrast exchange rate between tumor and
      fibroglandular BPH (P<0.04), providing improved delineation of intraprostatic
      tumor extent compared with conventional imaging techniques.

PMID- 10077031
TI  - Pharmacokinetics, safety, and tolerability of gadoversetamide injection
      (OptiMARK) in subjects with central nervous system or liver pathology and varying
      degrees of renal function.
AB  - The pharmacokinetic parameters, safety, and tolerability of OptiMARK
      (gadoversetamide injection), a gadolinium-based magnetic resonance imaging (MRI)
      contrast agent, were evaluated in 163 subjects with either central nervous system
      (CNS) or liver pathology with and without renal insufficiency, for which a
      contrast-enhanced MRI was indicated. A multicenter, double-blind, randomized,
      placebo-controlled, parallel-group design was used in which subjects received
      0.1, 0.3, or 0.5 mmol/kg of OptiMARK or placebo intravenously. Samples were
      analyzed for total gadolinium by inductively coupled plasma/mass spectrometry.
      Gadolinium pharmacokinetics were affected by renal impairment: area under the
      curve, half-life, and steady-state distribution volume significantly increased
      with declining renal function, while total body clearance decreased. In subjects
      with normal renal function, neither age, gender, nor liver versus CNS pathology
      altered gadolinium pharmacokinetics. No clinically significant changes from
      baseline were noted in vital signs, laboratory measures, electrocardiograms, or
      physical examinations. OptiMARK is safe and well-tolerated following a single
      intravenous injection in subjects with either liver or CNS pathology despite a
      prolonged elimination half-life in subjects with renal impairment.

PMID- 10077032
TI  - Ferumoxides-enhanced quantitative magnetic resonance imaging of the normal and
      abnormal bone marrow: preliminary assessment.
AB  - The purpose of our study was to assess the effects of intravenous administration
      of ferumoxides on normal and abnormal vertebral bone marrow T1 and T2 relaxation
      times. Changes in bulk T1 and T2 relaxation times induced by intravenous
      administration of ferumoxides were determined in the normal vertebral marrow of
      two healthy subjects and four patients. In the four patients, changes in bulk T1
      and T2 values induced by furomoxides injection were also determined in 12
      vertebral metastases. Relative to precontrast relaxation time values, bulk T1 and
      T2 values of normal bone marrow had declined by a mean of 24% and 19%,
      respectively, in the two subjects and the four patients 45 minutes after
      ferumoxides administration. Relative to precontrast values, bulk T1 and T2 values
      of abnormal bone marrow had decreased by a mean of 16% and 2%, respectively.
      Decreases in bulk T1 and T2 values in normal bone marrow and in bulk T1 values in
      metastases were statistically significant (P<0.001). Changes in bulk T2 values
      observed in metastases were not statistically significant. Quantitative MRI
      demonstrates that ferumoxides infusion induces a decrease in bulk T1 and T2
      relaxation times of normal bone marrow. It also suggests a lack of T2 shortening
      in bone metastases.

PMID- 10077033
TI  - Short- vs. long-circulating magnetoliposomes as bone marrow-seeking MR contrast
      agents.
AB  - We evaluated the relaxation enhancement and biodistribution of short- vs. long
      circulating magnetoliposomes as a new contrast agent for magnetic resonance (MR)
      imaging of bone marrow. Magnetoliposomes with (ML-PEG) and without (ML)
      incorporation of polyethylene glycol (PEG, Mw 2000) were prepared, measuring 40
      nm in diameter with 1-6 iron oxide crystals/vesicle. PEGylation selectively
      enhanced the T2 relaxivity of magnetoliposomes by 10% to 15%, with R1 and R2
      values of 3 and 240 s(-1)/mM at 1.5 T and 37 degrees C. ML (n = 6) and ML-PEG (n
      = 6) preparations were administered IV into young (6-8 weeks old) and adult (>1
      year old) Sprague-Dawley rats at 100 pmol Fe/kg. PEGylation increased blood half
      life (P<0.05 for t > 30 minutes), following a biexponential clearance with a long
      half-life of 53.2+/-13.2 minutes. The clearance of ML was monoexponential, with a
      half-life 7.4+/-0.4 minutes. MR imaging revealed a pronounced uptake in bone
      marrow, including the iliac bone, femur, tibia, and upper and lower vertebrae.
      The bone marrow uptake of ML-PEG was comparable to that of ML, with both reaching
      a plateau within 30 minutes following injection. Fast spin-echo T2-weighted
      imaging was found to provide optimal contrast enhancement and allowed a clear
      depiction of red to yellow marrow conversion due to normal aging. While the use
      of magnetoliposomes can provide the added benefit of therapeutic drug or gene
      delivery, further investigation is warranted to assess their usefulness in
      differentiating normal vs. abnormal marrow conditions.

PMID- 10077034
TI  - Mechanism of gadophrin-2 accumulation in tumor necrosis.
AB  - The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was
      investigated. Biodistribution studies and magnetic resonance imaging (MRI) and
      histologic/autoradiographic correlation were performed in xenograft mouse models
      bearing human tumors (HT 29, WiDr, LX 1). Binding of gadophrin-2 to DNA, lipids,
      or proteins was determined by fluorescence spectrophotometry. Protein binding was
      determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was
      low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor
      but higher in necrotic tumor regions and was readily detectable by MRI. Within a
      given tumor, the agent preferentially localized in the periphery of necrotic
      areas. Within these regions gadophrin-2 was bound to interstitial albumin and not
      other proteins, lipids, or DNA. Tumoral accumulation of gadophrin-2 most likely
      occurs through its binding to plasma albumin and subsequent slow extravasation
      into the tumor interstitium.

PMID- 10077035
TI  - CBF and CBV measurements by USPIO bolus tracking: reproducibility and comparison
      with Gd-based values.
AB  - The authors measured cerebral blood flow (CBF) and cerebral blood volume (CBV) by
      bolus tracking of a novel ultrasmall superparamagnetic iron oxide (USPIO)
      contrast agent (NC100150) and compared absolute and relative perfusion
      measurements with those obtained by a standard gadolinium-based contrast agent.
      They found a linear correlation between the two methods. A dose of 0.4 mg Fe/kg
      body weight was found to produce a signal drop similar to that of a standard 0.2
      mmol/kg gadodiamide injection using spin-echo echoplanar imaging (SE-EPI) at 1.0
      T. The measurements showed a high degree of reproducibility of repeated absolute
      as well as relative CBF and CBV values, lending further hope to the possibility
      of using magnetic resonance bolus tracking for routine CBF and CBV measurements.
      Finally, the authors present their initial experience with high-resolution, non
      EPI CBV maps obtained from steady-state levels of an intravascular
      superparamagnetic contrast agent.

PMID- 10077036
TI  - Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM
      dendrimer-DOTA-gadolinium chelates.
AB  - A series of high-generation (G) ethylenediamine-core polyamidoamine (PAMAM)
      dendrimers corresponding to G = 5, 7, 9, and 10 were conjugated with the
      bifunctional chelate 2-(4-isothiocyanatobenzyl)- 1,4,7,10-tetraazacyclododecane
      N,N',N",N"'-tetraacetate (p-SCN-Bz-DOTA). Gadolinium (III) ion was added to the
      macromolecules, and the 1/T1 and 1/T2 NMRD profiles were measured at 3 degrees,
      23 degrees, and 37 degrees C. The synthesis resulted in preparations that ranged
      from an average of 127 chelates and 96 Gd3+ ions per G = 5 dendrimer to an
      average of 3727 chelates and 1860 Gd3+ ions per G = 10 dendrimer. At 20 MHz and
      23 degrees C, the 1/T1 ion relaxivity increased from 30 mM(-1) s(-1) for the G =
      5 to 35 mM(-1) s(-1) for the G = 7 PAMAM dendrimer-DOTA-Gd, reaching a plateau at
      36 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. A similar plateau was
      observed for 1/T2 with values of 36 mM(-1) s(-1) for G = 5, 42 mM(-1) s(-1) for G
      = 7, and 45 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. This "saturation"
      of ion relaxivity for high-generation dendrimers occurred over the entire
      frequency range studied. The 1/T1 and 1/T2 relaxivities decreased as the
      temperature decreased for each generation of dendrimer studied, implying that
      slow water exchange of bound water molecules with the bulk solvent limits the
      relaxivity. In such circumstances, increases in the rotational correlation time
      of the macromolecules associated with higher generations of dendrimer does not
      result in significant increases in the ion relaxivity. Although the ion
      relaxivity does not increase, the total molecular relaxivities increased from
      2880 mM(-1) s(-1) to 66960 mM(-1) s(-1) for the G = 5 to the G = 10 dendrimer.
      The current findings are relevant for the design of high-generation dendrimer
      based receptor agents.

PMID- 10077037
TI  - The rete mirabile of the eel: a useful model for the study of transcapillary
      passage of MR contrast agents.
AB  - Our purpose was to study the capillary leakage of MR contrast media using a pure
      capillary model, the rete mirabile of the eel. The rete is a countercurrent
      exchange organ composed of an arterial and a venous capillary system that can be
      catheterized and perfused. Substances are introduced at the arterial input by a
      constant infusion, and their steady-state concentrations are measured at the
      arterial and venous outputs. The capillary leakage of four MR contrast agents--Gd
      DOTA(MW = 561 D), carboxymethyldextran-Gd-DTPA (MW = 38,900 D), albumin-Gd-DTPA
      (MW = 92,000 D), AMI-227 (400,000 D<MW<900,000 D)--was characterized by reference
      to radioactive tracers (3HHO, 22Na, 14C-sucrose, 125I-albumin) by two parameters.
      These parameters were the concentration ratio of the venous output over the
      arterial input [C(VOUT)(%)] and the permeability coefficient (P). The
      transcapillary pathway mechanisms for carboxymethyldextran-Gd-DTPA and albumin-Gd
      DTPA were studied by electron microscopy. P values for Gd-DOTA (9.4+/-3.6 x 10(
      7) cm/s) and albumin-Gd-DTPA (11.8+/-5.5 x 10(-7) cm/s) were close to P values
      for 14C-sucrose, while P values for carboxymethyldextran-Gd-DTPA (6.4+/-4.9 x 10(
      7) cm/sec) were similar to P values for 125I-albumin. The lowest permeability was
      observed with AMI-227 (2.7+/-2 x 10(-7) cm/sec). Vesicular transport was
      demonstrated for carboxymethyldextran-Gd-DTPA and albumin-Gd-DTPA. The
      transcapillary passage of several MR contrast agents can be characterized with
      the rete mirabile model. Molecular weight is the major factor influencing
      transport.

PMID- 10077038
TI  - Incidental detection of acute myocardial infarction during routine performance of
      three-dimensional dynamic MR angiographic study with dynamic injection of
      gadolinium.
AB  - We report on the MR appearance of acute myocardial infarction in a 61-year-old
      man with Ehlers-Danlos syndrome using motion-independent, T2-weighted echo train
      spin echo and immediate post-gadolinium three-dimensional gradient echo imaging
      performed as an MRI angiographic study of the aortic arch. The region of acute
      infarction was of high signal intensity on the T2-weighted images and
      demonstrated greatly diminished enhancement on the immediate post-gadolinium
      three-dimensional gradient echo images. MRI findings showed good correlation with
      autopsy specimens obtained within 24 hours of the MRI study.

PMID- 10077039
TI  - Mangafodipir trisodium: effects on T2- and T1-weighted MR cholangiography.
AB  - The purpose of this study was to determine the effects of mangafodipir trisodium
      on heavily T2-weighted magnetic resonance cholangiography (MRC) images and on
      functional T1-weighted MRC. Pre- and post-mangafodipir trisodium heavily T2
      weighted MRC and fat-suppressed T1-weighted three-dimensional (3D) gradient-echo
      MRC images were obtained in a patient with a prior cholecystectomy and a long
      cystic duct remnant that had apparent biliary stasis. Multiplanar reconstructed
      images were created. The precontrast T2-weighted MRC showed a long cystic duct
      remnant and a normal common bile duct (CBD). The postcontrast T2-weighted MRC
      showed loss of CBD signal, but persistent signal in the cystic duct remnant due
      to biliary stasis. Post-mangafodipir T1-weighted 3D gradient-echo images showed
      the main right and left hepatic ducts, but the cystic duct was not depicted.
      Conventional T2-weighted MRC sequences should not be obtained after administering
      mangafodipir trisodium because this contrast agent decreases the T2 and therefore
      the signal intensity of bile within normally functioning bile ducts. Functional
      MRC images can be acquired by using a post-mangafodipir T1-weighted technique.

PMID- 10077040
TI  - Response to neoadjuvant chemotherapy best predicts survival after curative
      resection of gastric cancer.
AB  - OBJECTIVE: In Western populations, long-term survival rates after curative
      resection of gastric cancer remain extremely poor. The lack of effective adjuvant
      therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we
      have conducted three separate phase II trials using neoadjuvant chemotherapy to
      treat patients with potentially resectable gastric cancer. The present study was
      conducted to evaluate whether response to neoadjuvant chemotherapy is predictive
      of survival in patients with resectable gastric cancer. METHODS: Eighty-three
      patients with pathologically confirmed gastric adenocarcinoma were treated with
      neoadjuvant chemotherapy before planned surgical resection. Response was assessed
      by upper gastrointestinal series, endoscopy, computed tomography scan, and
      pathologic examination. RESULTS: For the three phase II trials, clinical response
      rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic
      response. Sixty-one patients (73%) underwent a curative resection. Median follow
      up was 26 months. Univariate analysis revealed T stage, number of positive nodes,
      and response to chemotherapy to be significant predictors of overall survival.
      However, on multivariate analysis, response to chemotherapy was found to be the
      only independent prognostic factor. CONCLUSIONS: Response to neoadjuvant
      chemotherapy is the single most important predictor of overall survival after
      neoadjuvant chemotherapy for gastric cancer. These findings support further
      evaluation of neoadjuvant approaches in the treatment of this disease.

PMID- 10077041
TI  - Neoadjuvant therapy.

PMID- 10077042
TI  - Split liver transplantation.
AB  - OBJECTIVE: This study reviews the indications, technical aspects, and experience
      with ex vivo and in situ split liver transplantation. BACKGROUND: The shortage of
      cadaveric donor livers is the most significant factor inhibiting further
      application of liver transplantation for patients with end-stage liver disease.
      Pediatric recipients, although they represent only 15% to 20% of the liver
      transplant registrants, suffer the greatest from the scarcity of size-matched
      cadaveric organs. Split liver transplantation provides an ideal means to expand
      the donor pool for both children and adults. METHODS: This review describes the
      evolution of split liver transplantation from reduced liver transplantation and
      living-related liver transplantation. The two types of split liver
      transplantation, ex vivo and in situ, are compared and contrasted, including the
      technique, selection of patients for each procedure, and the most current
      results. RESULTS: Ex vivo splitting of the liver is performed on the bench after
      removal from the cadaver. It is usually divided into two grafts: segments 2 and 3
      for children, and segments 4 to 8 for adults. Since 1990, 349 ex vivo grafts have
      been reported. Until recently, graft and patient survival rates have been lower
      and postoperative complication rates higher in ex vivo split grafts than in whole
      organ cadaveric transplantation. Further, the use of ex vivo split grafts has
      been relegated to the elective adult patient because of the high incidence of
      graft dysfunction (right graft) when placed in an emergent patient. Reasons for
      the poor function of ex vivo splits except in elective patients have focused on
      graft damage due to prolonged cold ischemia times and rewarming during the long
      benching procedure. In situ liver splitting is accomplished in a manner identical
      to the living donor procurement. This technique for liver splitting results in
      the same graft types as in the ex vivo technique. However, graft and patient
      survival rates reported for in situ split livers have exceeded 85% and 90%,
      respectively, with a lower incidence of postoperative complications, including
      biliary and reoperation for bleeding. These improved results have also been
      observed in the urgent patient. CONCLUSION: Splitting of the cadaveric liver
      expands the donor pool of organs and may eliminate the need for living-related
      donation for children. Recent experience with the ex vivo technique, if applied
      to elective patients, results in patient and graft survival rates comparable to
      whole-organ transplantation, although postoperative complication rates are
      higher. In situ splitting provides two grafts of optimal quality that can be
      applied to the entire spectrum of transplant recipients: it is the method of
      choice for expanding the cadaver liver donor pool.

PMID- 10077043
TI  - Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.
AB  - OBJECTIVE: The authors report on the surgical techniques and protocol for
      perioperative care that have yielded a zero hospital mortality rate in 110
      consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC).
      The hepatectomy results are analyzed with the aim of further reducing the
      postoperative morbidity rate. SUMMARY BACKGROUND DATA: In recent years,
      hepatectomy has been performed with a mortality rate of <10% in patients with
      HCC, but a zero hospital mortality rate in a large patient series has never been
      reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and
      perioperative management in hepatectomy for HCC have evolved yearly into a final
      standardized protocol that reduced the hospital mortality rate from 28% in 1989
      to 0% in 1996 and 1997. METHODS: Surgical techniques were designed to reduce
      intraoperative blood loss, blood transfusion, and ischemic injury to the liver
      remnant in hepatectomy. Postoperative care was focused on preservation and
      promotion of liver function by providing adequate tissue oxygenation and
      immediate postoperative nutritional support that consisted of branched-chain
      amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and
      phosphate. The pre-, intra-, and postoperative data were collected prospectively
      and analyzed each year to assess the influence of the evolving surgical
      techniques and perioperative care on outcome. RESULTS: Of 330 patients undergoing
      hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in
      161 (49%) and 108 (33%) patients, respectively. There were no significant changes
      in the patient characteristics throughout the 9-year period, but there were
      significant reductions in intraoperative blood loss and blood transfusion
      requirements. From 1994 to 1997, the median blood transfusion requirement was 0
      ml, and 64% of the patients did not require a blood transfusion. The
      postoperative morbidity rate remained the same throughout the study period.
      Complications in the patients operated on during 1996 and 1997 were primarily
      wound infections; the potentially fatal complications seen in the early years,
      such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By
      univariate analysis, the volume of blood loss, volume of blood transfusions, and
      operation time were correlated positively with postoperative morbidity rates in
      1996 and 1997. Stepwise logistic regression analysis revealed that the operation
      time was the only parameter that correlated significantly with the postoperative
      morbidity rate. CONCLUSION: With appropriate surgical techniques and
      perioperative management to preserve function of the liver remnant, hepatectomy
      for HCC can be performed without hospital deaths. To improve surgical outcome
      further, strategies to reduce the operation time are being investigated.

PMID- 10077044
TI  - Improvement in quality of life measures after laparoscopic antireflux surgery.
AB  - OBJECTIVE: To determine if patients with gastroesophageal reflux "well controlled
      medically" had a different quality of life from those with residual symptoms
      receiving aggressive medical therapy, and to determine whether laparoscopic
      antireflux surgery significantly altered quality of life in patients with
      gastroesophageal reflux. SUMMARY BACKGROUND DATA: Clinical determinants of
      outcome may not adequately reflect the full impact of therapy. The medical
      outcomes study short form (SF-36) is a well-validated questionnaire that assays
      eight specific health concepts in three general fields. It may provide a more
      sensitive tool for judging the success of antireflux therapy. METHODS: A total of
      345 patients undergoing laparoscopic antireflux surgery completed at least one
      questionnaire during the study period. Preoperative questionnaires were completed
      by 290 patients, 223 completed a questionnaire 6 weeks after surgery, and 50
      completed the same questionnaire 1 year after surgery. A subgroup of 70 patients
      was divided before surgery into two groups on the basis of their response to
      standard medical therapy. RESULTS: Preoperative scores were extremely low. All
      eight SF-36 health categories improved significantly 6 weeks and 1 year after
      surgery. In the 70-patient subgroup, 53 patients (76%) underwent laparoscopic
      antireflux surgery because of symptoms refractory to medical therapy and 17
      patients (24%) reported that their symptoms were well controlled but elected to
      have surgery because they wished to be medication-free. The preoperative quality
      of life scores of these two patient groups were equivalent in all but one
      category. Postoperative scores were significantly improved in all categories and
      indistinguishable between the two groups. CONCLUSIONS: Laparoscopic antireflux
      surgery is an effective therapy for patients with gastroesophageal reflux and may
      be more effective than medical therapy at improving quality of life.

PMID- 10077045
TI  - Erythromycin enhances early postoperative contractility of the denervated whole
      stomach as an esophageal substitute.
AB  - OBJECTIVE: To determine whether early postoperative administration of
      erythromycin accelerates the spontaneous motor recovery process after elevation
      of the denervated whole stomach up to the neck. SUMMARY BACKGROUND DATA:
      Spontaneous motor recovery after gastric denervation is a slow process that
      progressively takes place over years. METHODS: Erythromycin was administered as
      follows: continuous intravenous (i.v.) perfusion until postoperative day 10 in
      ten whole stomach (WS) patients at a dose of either 1 g (n = 5) or 2 g (n = 5)
      per day; oral intake at a dose of 1 g/day during 1.5 to 8 months after surgery in
      11 WS patients, followed in 7 of them by discontinuation of the drug during 2 to
      4 weeks. Gastric motility was assessed with intraluminal perfused catheters in
      these 21 patients, in 23 WS patients not receiving erythromycin, and in 11
      healthy volunteers. A motility index was established by dividing the sum of the
      areas under the curves of >9 mmHg contractions by the time of recording. RESULTS:
      The motility index after IV or oral administration of erythromycin at and after
      surgery was significantly higher than that without erythromycin (i.v., 1 g: p =
      0.0090; i.v., 2 g: p = 0.0090; oral, 1 g: p = 0.0017). It was similar to that in
      healthy volunteers (i.v., 1 g: p = 0.2818; oral, 1 g: p = 0.7179) and to that in
      WS patients with >3 years of follow-up who never received erythromycin (i.v., 1
      g: p = 0.2206; oral, 1 g: p = 0.8326). The motility index after discontinuation
      of the drug was similar or superior to that recorded under medication in four
      patients who did not experience any modification of their alimentary comfort,
      whereas it dropped dramatically parallel to deterioration of the alimentary
      comfort in three patients. CONCLUSIONS: Early postoperative contractility of the
      denervated whole stomach pulled up to the neck under either i.v. or oral
      erythromycin is similar to that recovered spontaneously beyond 3 years of follow
      up. In some patients, this booster effect persists after discontinuation of the
      drug.

PMID- 10077046
TI  - Introduction of appendiceal CT: impact on negative appendectomy and appendiceal
      perforation rates.
AB  - OBJECTIVE To evaluate the impact of appendiceal computed tomography (CT)
      availability on negative appendectomy and appendiceal perforation rates. SUMMARY
      BACKGROUND DATA: Appendiceal CT is 98% accurate. However, its impact on negative
      appendectomy and appendiceal perforation rates has not been reported. METHODS:
      The authors reviewed the medical records of 493 consecutive patients who
      underwent appendectomy between 1992 and 1995, 209 consecutive patients who
      underwent appendectomy in 1997 (59% of whom had appendiceal CT), and 206 patients
      who underwent appendiceal CT in 1997 without subsequent appendectomy. RESULTS:
      Before appendiceal CT, 98/493 patients (20%) taken to surgery had a normal
      appendix. After CT availability, 15/209 patients (7%) taken to surgery had a
      normal appendix; 7 patients did not have CT, 5 patients had surgery despite a
      negative CT, and 3 patients had a false-positive CT. Negative appendectomy rates
      were lowered overall (20% to 7%), in men (11% to 5%), in women (35% to 11%), in
      boys (10% to 5%), and in girls (18% to 12%). Appendiceal perforation rates
      dropped from 22% to 14% after CT availability. CT excluded appendicitis in 206
      patients in 1997 who avoided appendectomy and identified alternative diagnoses in
      105 of these patients (51%). CONCLUSION: The availability of appendiceal CT
      coincided with a drop in the negative appendectomy rate from 20% to 7% in all
      patients, and to only 3% in patients with a positive CT. Perforation rates
      decreased from 22% to 14%. Appendiceal CT can be advocated in nearly all female
      and many male patients.

PMID- 10077047
TI  - Combined molecular and clinical approaches for the identification of families
      with familial adenomatous polyposis coli.
AB  - OBJECTIVE: Using an interdisciplinary clinical and molecular approach, the
      authors identified APC germline mutations in families with familial adenomatous
      polyposis (FAP). Correlation of mutation site with disease manifestation and the
      impact of molecular data on clinical proceedings were examined. SUMMARY
      BACKGROUND DATA: Germline mutations in the APC gene predispose to FAP.
      Established and proposed genotype-phenotype correlations as well as the influence
      of mutation site on surgical procedures have been reported. The predictive value
      of APC mutation analysis for disease manifestation and therapeutic decision
      making needs to be investigated further. METHODS: One hundred twenty-three
      kindreds of the local FAP registry were included in this study. CHRPE phenotype
      was defined as at least one large characteristic lesion or a total of four
      lesions in both eyes. APC mutations were identified by protein truncation test
      and automated DNA sequencing from patient lymphocyte DNA and RNA. RESULTS: APC
      germline mutations were identified in 85/123 families with FAP. They were located
      between codons 213 and 1581 of the APC gene and displayed distinct genotype
      phenotype correlations. CHRPE status facilitated mutation analysis by
      discriminating regions of interest within the APC coding region. Severe
      manifestations of desmoids were restricted to mutations between codons 1444
      through 1581. Whereas 91% (75/82) of at-risk persons were excluded as mutation
      carriers, APC germline mutations were detected before clinical examination in 9%
      (7/82) of at-risk persons. One patient agreed to endoscopy only after mutation
      detection. CONCLUSIONS: This study supports the feasibility of combined molecular
      and clinical screening of families with FAP and may provide a guideline for
      routine presymptomatic molecular diagnostics in a clinical laboratory.

PMID- 10077048
TI  - Prediction of common bile duct stones by noninvasive tests.
AB  - OBJECTIVE: To define accurate and useful predictors of common bile duct stones
      (CBDS). SUMMARY BACKGROUND DATA: The ability to predict CBDS with noninvasive
      tests can avoid unnecessary, costly, or risky procedures. METHODS: All patients
      referred for examination for CBDS by endoscopic ultrasonography (EUS) from 1993
      1996 were prospectively entered in a database. In a first sample selected
      randomly from the whole population, predictors of CBDS were determined by
      univariate analysis and logistic regression. Predictors were subsequently tested
      in that sample and in the rest of the population. A separate analysis was done
      for patients planned for cholecystectomy. RESULTS: Eight hundred and eighty
      patients (328 men, 552 women), aged 57.8 +/- 17 years (range 16-94), were
      included. The prevalence of CBDS was 18.8%. Age, serum levels of bilirubin,
      aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase
      (GGT), and alkaline phosphatase, and the existence of jaundice and fever, a
      dilated bile duct, and a pathologic gallbladder were found to be associated with
      CBDS. Logistic regression was undertaken separately for patients younger than 70
      years (predictors: GGT >7 x normal; pathologic gallbladder; dilated bile duct)
      and older than 70 years (predictors: GGT >7 x normal; fever > 38 degrees C;
      dilated bile duct). Odds ratios were 3 to 6.7. The model was satisfactorily
      applicable to the second sample; age <70 years: chi2 = 3.3 (NS); age >70 years:
      chi2 = 3.8 (NS). In patients younger than age 70 and planned for cholecystectomy,
      the combination of the level of GGT and dilated bile duct predicted CBDS
      accurately. CONCLUSIONS: A simple screening of patients at risk for CBDS can be
      achieved with three predictive criteria adapted for the patient's age.

PMID- 10077049
TI  - Continuous versus intermittent portal triad clamping for liver resection: a
      controlled study.
AB  - OBJECTIVE: The authors compared the intra- and postoperative course of patients
      undergoing liver resections under continuous pedicular clamping (CPC) or
      intermittent pedicular clamping (IPC). SUMMARY BACKGROUND DATA: Reduced blood
      loss during liver resection is achieved by pedicular clamping. There is
      controversy about the benefits of IPC over CPC in humans in terms of
      hepatocellular injury and blood loss control in normal and abnormal liver
      parenchyma. METHODS: Eighty-six patients undergoing liver resections were
      included in a prospective randomized study comparing the intra- and postoperative
      course under CPC (n = 42) or IPC (n = 44) with periods of 15 minutes of clamping
      and 5 minutes of unclamping. The data were further analyzed according to the
      presence (steatosis >20% and chronic liver disease) or absence of abnormal liver
      parenchyma. RESULTS: The two groups of patients were similar in terms of age,
      sex, nature of the liver tumors, results of preoperative assessment, proportion
      of patients undergoing major or minor hepatectomy, and nature of nontumorous
      liver parenchyma. Intraoperative blood loss during liver transsection was
      significantly higher in the IPC group. In the CPC group, postoperative liver
      enzymes and serum bilirubin levels were significantly higher in the subgroup of
      patients with abnormal liver parenchyma. Major postoperative deterioration of
      liver function occurred in four patients with abnormal liver parenchyma, with two
      postoperative deaths. All of them were in the CPC group. CONCLUSIONS: This
      clinical controlled study clearly demonstrated the better parenchymal tolerance
      to IPC over CPC, especially in patients with abnormal liver parenchyma.

PMID- 10077050
TI  - Prolonged continuous or intermittent vascular inflow occlusion during
      hemihepatectomy in pigs.
AB  - OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy
      model in pigs after prolonged continuous or intermittent vascular inflow
      occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood
      loss during liver resections can be prevented by temporary vascular inflow
      occlusion, consequently leading to ischemia and reperfusion injury in the remnant
      liver. Previously, in a pig liver resection model in which only limited I/R
      injury was induced during brief (90 min) vascular inflow occlusion, the authors
      demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to
      intermittent (INT). This liver resection study on pigs was undertaken to assess
      I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0
      +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight
      subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6
      hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed
      within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver
      resection was performed in control experiments (n = 6). Microvascular damage was
      assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early
      sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2
      during reperfusion. Hepatocellular damage was tested by plasma concentrations of
      aspartate aminotransferase (AST), alanine aminotransferase, and lactate
      dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of
      reperfusion, compared to preischemic uptake, was unaltered in the control group,
      but was significantly reduced in both resection groups. However, more HA was
      taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%,
      respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6
      hours of reperfusion more closely returned to preischemic configuration in the
      INT group than in the CNT group, indicating reduced microcirculatory disturbances
      after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was
      significantly increased in both CNT and INT groups. Lower AST levels, however,
      were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and
      603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic
      vascular inflow occlusion during prolonged liver ischemia in pigs resulted in
      less microcirculatory and hepatocellular injury, compared to continuous
      occlusion. Intermittent clamping is preferable when prolonged periods of vascular
      inflow occlusion are applied during liver resections.

PMID- 10077051
TI  - Phospholipase A2 mediates nitric oxide production by alveolar macrophages and
      acute lung injury in pancreatitis.
AB  - OBJECTIVE: Reportedly, nitric oxide (NO) derived from alveolar macrophages (AMs)
      and increased serum phospholipase A2 (PLA2) activity are associated with the
      pathogenesis of lung injury in acute pancreatitis. The authors examined the
      possibility that PLA2 causes, in part, the induction of NO production by AMs in
      pancreatitis. METHODS: Pancreatitis was induced in rats by selective pancreatic
      duct ligation (SPL). AMs were stimulated with PLA2 or SPL rat serum, with or
      without administration of the PLA2 inhibitor quinacrine. Then NO production from
      the AMs was measured by the Griess method, inducible NO synthase mRNA expression
      of AMs was analyzed by the reverse transcription-polymerase chain reaction, and
      cytotoxic effects of AMs on human umbilical vein endothelial cells was examined
      by a 51Cr release assay. In vivo, the effect of quinacrine on lung injury was
      determined by measuring the arterial blood oxygen pressure (PaO2), lung weight,
      and lung permeability using Evans blue dye concentration of SPL rat. RESULTS: In
      vitro, the serum with high PLA2 activity induced NO production by rat AMs. PLA2
      (50 ng/ml) induced significant amounts of NO production, inducible NO synthase
      mRNA expression, and cytotoxicity toward the human umbilical vein endothelial
      cells in normal rat AMs, and these activities were significantly inhibited by
      quinacrine. In vivo, rats with pancreatitis that were given quinacrine showed
      decreased concentrations of NO2- and NO3- in the bronchoalveolar lavage fluid,
      and the PaO2, lung edema, and lung permeability were improved significantly.
      CONCLUSION: PLA2 induces AMs to release NO, which contributes to lung injury in
      acute pancreatitis. This lung injury was prevented by the administration of the
      PLA2 inhibitor quinacrine.

PMID- 10077052
TI  - Reexploration for periampullary carcinoma: resectability, perioperative results,
      pathology, and long-term outcome.
AB  - OBJECTIVE: This single-institution experience retrospectively reviews the
      outcomes of patients undergoing reexploration for periampullary carcinoma at a
      high-volume center. SUMMARY BACKGROUND DATA: Many patients are referred to
      tertiary centers with periampullary carcinoma after their tumors were deemed
      unresectable at previous laparotomy. In carefully selected patients, tumor
      resection is often possible; however, the perioperative results and long-term
      outcome have not been well defined. METHODS: From November 1991 through December
      1997, 78 patients who underwent previous exploratory laparotomy and/or palliative
      surgery for suspected periampullary carcinoma underwent reexploration. The
      operative outcome, resectability rate, pathology, and long-term survival rate
      were compared with 690 concurrent patients who had not undergone previous
      exploratory surgery. RESULTS: Fifty-two of the 78 patients (67%) undergoing
      reexploration underwent successful resection by pancreaticoduodenectomy; the
      remaining 26 patients (34%) were deemed to have unresectable disease. Compared
      with the 690 patients who had not undergone recent related surgery, the patients
      in the reoperative group were similar with respect to gender, race, and
      resectability rate but were significantly younger. The distribution of
      periampullary cancers by site in the reoperative group undergoing
      pancreaticoduodenectomy (n = 52) was 60%, 19%, 15%, and 6% for pancreatic,
      ampullary, distal bile duct, and duodenal tumors, respectively. These figures
      were similar to the 65%, 14%, 16% and 5% for resectable periampullary cancers
      found in the primary surgery group (n = 460). Intraoperative blood loss and
      transfusion requirements did not differ between the two groups. However, the mean
      operative time was 7.4 hours in the reoperative group, significantly longer than
      in the control group. On pathologic examination, reoperative patients had smaller
      tumors, and the percentage of patients with positive lymph nodes in the resection
      specimen was significantly less. The incidence of positive margins was similar
      between the two groups. Postoperative lengths of stay, complication rates, and
      perioperative mortality rates were not higher in reoperative patients. The long
      term survival rate was similar between the two resected groups, with a median
      survival of 24 months in the reoperative group and 20 months in those without
      previous exploration. CONCLUSIONS: These data demonstrate that patients
      undergoing reoperation for periampullary carcinoma have similar resectability,
      perioperative morbidity and mortality, and long-term survival rates as patients
      undergoing initial exploration. The results suggest that selected patients
      considered to have unresectable disease at previous surgery should undergo
      restaging and reexploration at specialized high-volume centers.

PMID- 10077053
TI  - Bilateral neck exploration under hypnosedation: a new standard of care in primary
      hyperparathyroidism?
AB  - OBJECTIVE: The authors review their experience with initial bilateral neck
      exploration under local anesthesia and hypnosedation for primary
      hyperparathyroidism. Efficacy, safety, and cost effectiveness of this new
      approach are examined. BACKGROUND: Standard bilateral parathyroid exploration
      under general anesthesia is associated with significant risk, especially in an
      elderly population. Image-guided unilateral approaches, although theoretically
      less invasive, expose patients to the potential risk of missing multiple adenomas
      or asymmetric hyperplasia. Initial bilateral neck exploration under hypnosedation
      may maximize the strengths of both approaches while minimizing their weaknesses.
      METHODS: In a consecutive series of 121 initial cervicotomies for primary
      hyperparathyroidism performed between 1995 and 1997, 31 patients were selected on
      the basis of their own request to undergo a conventional bilateral neck
      exploration under local anesthesia and hypnosedation. Neither preoperative
      testing of hypnotic susceptibility nor expensive localization studies were done.
      A hypnotic state (immobility, subjective well-being, and increased pain
      thresholds) was induced within 10 minutes; restoration of a fully conscious state
      was obtained within several seconds. Patient comfort and quiet surgical
      conditions were ensured by local anesthesia of the collar incision and minimal
      intravenous sedation titrated throughout surgery. Both peri- and postoperative
      records were examined to assess the safety and efficacy of this new approach.
      RESULTS: No conversion to general anesthesia was needed. No complications were
      observed. All the patients were cured with a mean follow-up of 18 +/- 12 months.
      Mean operating time was <1 hour. Four glands were identified in 84% of cases,
      three glands in 9.7%. Adenomas were found in 26 cases; among these, 6 were
      ectopic. Hyperplasia, requiring subtotal parathyroidectomy and transcervical
      thymectomy, was found in five cases (16.1%), all of which had gone undetected by
      localization studies when requested by the referring physicians. Concomitant
      thyroid lobectomy was performed in four cases. Patient comfort and recovery and
      surgical conditions were evaluated on visual analog scales as excellent.
      Postoperative analgesic consumption was minimal. Mean length of hospital stay was
      1.5 +/- 0.5 days. CONCLUSIONS: Initial bilateral neck exploration for primary
      hyperparathyroidism can be performed safely, efficiently, and cost-effectively
      under hypnosedation, which may therefore be proposed as a new standard of care.

PMID- 10077054
TI  - Ten-year trend in survival and resource utilization at a level I trauma center.
AB  - OBJECTIVE: To determine the impact of increasing trauma center experience over
      time on survival and resource utilization. METHODS: The authors studied a
      retrospective cohort at a single level I trauma center over a 10-year period,
      from 1986 to 1995. Patients included all hospital admissions and emergency
      department deaths. The main outcome measures were the case-fatality rate adjusted
      for injury severity, hospital length of stay, and costs. RESULTS: A total of
      25,979 patients were admitted or died. The number of patients per year increased,
      from 2063 in 1986 to 3313 in 1995. The proportion of patients transferred from
      another institution increased from 16.2% to 34.4%. Although mean length of stay
      declined by 28.4%, from 9.5 to 6.8 days, costs increased by 16.7%, from $14,174
      to $16,547. The use of specific radiologic investigations increased; the
      frequency of operative procedures either remained unchanged (craniotomy, fracture
      fixation) or decreased (celiotomy). After adjusting for injury severity and
      demographic factors, the mortality rate decreased over 10 years. The improvement
      in survival was confined to patients with an injury severity score > or =16.
      CONCLUSION: Over a 10-year period, the case-fatality rate declined in patients
      with severe injuries. Overall acute care costs increased, partially because of
      the increased use of radiologic investigations. Even in otherwise established
      trauma centers, increasing cumulative experience results in improved survival
      rates in the most severely injured patients. These data suggest that experience
      contributes to a decrease in mortality rate after severe trauma and that
      developing trauma systems should consider this factor and limit the number of
      designated centers to maximize cumulative experience at individual centers.

PMID- 10077055
TI  - Management of true aneurysms of the pancreaticoduodenal arteries.
AB  - OBJECTIVE: To review the authors' recent experience and that of the literature
      since 1973 and to provide management guidelines for true aneurysms of the
      pancreaticoduodenal arteries (PDA). SUMMARY BACKGROUND DATA: True aneurysms of
      the PDA are rare, with a total of only 52 cases reported since 1973. METHODS: Six
      patients were admitted to the authors' institution between 1985 and 1995 for
      rupture of a true aneurysm of the PDA. They were analyzed with regard to the mode
      of presentation, preoperative workup, management, and outcome. RESULTS: All
      patients had severe epigastric pain from retroperitoneal hemorrhage. Computed
      tomography scanning and angiography were performed in all cases. Aneurysms ranged
      from 0.7 to 1.2 cm (median 0.9 cm). The celiac axis was stenotic or occluded in
      five cases. Three patients underwent emergency pancreatoduodenectomy. Two of them
      survived. In one case, section of the median arcuate ligament was associated with
      the procedure, and the patient died from an aortic dissection. Embolization was
      performed in the last three patients. The procedure was definitive in two cases.
      In one, hemorrhage recurred 8 days later and required surgical ligation of the
      bleeding artery. CONCLUSIONS: The authors recommend rapid treatment of all true
      aneurysms of the PDA. Because most of these aneurysms result from a stenosis of
      the celiac axis, selective embolization may help to preserve patency of the PDA
      and should, therefore, be the primary therapeutic choice in ruptured aneurysms.
      Close follow-up is mandatory because of possible recurrent bleeding. Appropriate
      and expeditious management of true PDA aneurysms should help reduce the mortality
      rate.

PMID- 10077056
TI  - Return of lymphatic function after flap transfer for acute lymphedema.
AB  - OBJECTIVE: The goals of this work were to develop animal models of lymphedema and
      tissue flap transfer, and to observe physiologic changes in lymphatic function
      that occur in these models over time, both systemically with lymphoscintigraphy
      (LS) and locally using fluorescence microlymphangiography (FM). SUMMARY
      BACKGROUND DATA: Although lymphedema has been managed by a combination of medical
      and surgical approaches, no effective long-term cure exists. Surgical attempts
      aimed at reconnecting impaired lymphatic channels or bypassing obstructed areas
      have failed. METHODS: The tails of rats (A groups) and mice (B groups) were used
      because of their different features. Lymphedema was created by ligation of the
      lymphatics at the tail base and quantified by diameter measurements there. In the
      experimental group, rectus abdominis myocutaneous flap was transferred across the
      ligation. In addition to the ligation (A1 and B1) and ligation + flap (A2 and B2)
      groups, three control groups were included: sham flap with ligation (B4), sham
      flap alone (B5), and normal (A3 and B3) animals. Observations were made at weekly
      time points for lymphatic function and continuity. RESULTS: Lymphedema was
      successfully created in the mouse ligation groups (B1 and B4) and sustained for
      the entire length of observation (up to 14 weeks). Lymphatic continuity was
      restored in those animals with transferred flaps across the ligation site (A2 and
      B2), as seen both by LS and FM. Sham flaps did not visibly affect lymphatic
      function nor did they cause any visible swelling in the tail. CONCLUSIONS: Acute
      lymphedema developing after ligation of tail lymphatics in mice can be prevented
      by myocutaneous flap transfer. Restored lymphatic continuity and function were
      demonstrable using lymphoscintigraphy and fluorescence microlymphangiography.

PMID- 10077057
TI  - Norman Barrett, "doyen of esophageal surgery".

PMID- 10077058
TI  - Surgeon-related factors and outcome in rectal cancer.

PMID- 10077059
TI  - Surgeon-related factors and outcome in rectal cancer.

PMID- 10077060
TI  - Surgeon-related factors and outcome in rectal cancer.

PMID- 10077061
TI  - Routine use of prophylactic renal-dose dopamine in surgical patients is not
      supported by the literature.

PMID- 10077062
TI  - The relationships between phenotypic expression in patients with familial
      adenomatous polyposis (FAP) and the site of mutations in the adenomatous
      polyposis coli (APC) gene.

PMID- 10077063
TI  - Reversal of a small-bowel segment so as to decrease transit time and increase the
      absorptive capability of the bowel.

PMID- 10077064
TI  - Nasal expansion in the fetal lamb: a first step toward management of cleft nasal
      deformity in utero.
AB  - The cleft nasal deformity, a combination of malpositioned cartilage and tissue
      and postrepair scarring, is a difficult problem to correct. To harness the
      potential of scarless fetal wound healing, in utero repair of cleft lip and
      palate deformities has been studied but the fetal cleft nose deformity has not
      been addressed. The purpose of this study was to manipulate the fetal nasal shape
      in utero as a first step toward restoration of normal nasal form in cleft nasal
      deformities. To do this, preformed hypertonic sponges were placed into the right
      nostril of eight fetal lambs during the second trimester (when scarless cutaneous
      wound repair is known to occur). Then, the size and shape of fetal nasal
      structures were analyzed after selected time periods (1, 2, and 6 weeks) with
      measurements, routine histologic examination, and three-dimensional computed
      tomographic scans of the experimentally expanded noses compared with the control
      nonexpanded noses of the birth twins or age-matched specimens. Results showed
      that experimentally expanded nasal structures had markedly increased in septal
      length measurement, in nostril area (doubled), and in intranasal volume (more
      than doubled). Histology showed normal cellular elements without scarring in the
      tissue sections from the expanded nasal areas. In conclusion, the shape of nasal
      tissue can be manipulated without scarring in second-trimester fetal lambs after
      placement of a nasal expansion device. This study is an experimental first step
      toward restoring normal nasal form by repositioning alar cartilages and soft
      tissue during fetal cleft repair.

PMID- 10077065
TI  - Soft-tissue facial morphometry from 6 years to adulthood: a three-dimensional
      growth study using a new modeling.
AB  - A recently introduced three-dimensional computerized system with landmark
      representation of the soft-tissue facial surface allows noninvasive and fast
      quantitative study of facial growth. The aims of the present investigation were
      (1) to quantify growth changes in soft-tissue facial morphology, (2) to evaluate
      sex differences in growth patterns, and (3) to provide reference data for
      selected angular and linear measurements that could be of interest for the
      objective analysis of maxillofacial surgery or orthodontic patients. The three
      dimensional coordinates of 22 standardized facial landmarks were automatically
      collected by automated infrared photogrammetry using the three-dimensional facial
      morphometry method in a mixed longitudinal and cross-sectional study, in which
      2023 examinations were obtained in 1348 healthy nonpatient subjects between 6
      years of age and young adulthood. Selected parameters (angles, linear distances,
      and ratios) were calculated and averaged for age and sex. Male values were
      compared with female values by means of Student's t test. Within each age group,
      linear distances were significantly larger in boys than in girls (p < 0.05) with
      some exceptions coinciding with the earlier female growth spurt, whereas angular
      measurements did not show a corresponding sexual dimorphism. Linear distances in
      girls had almost reached adult dimensions in the 12-to-13-year-old age group,
      whereas in boys a large increase was still to occur. This was most evident in the
      middle third of the face, where both sexes showed almost the same dimension and
      amount of growth up to the age of 13, with significant differences afterward,
      boys being larger than girls. On the contrary, in the lower third of the face,
      significant differences occurred throughout the whole investigated period, boys
      being always larger than girls. The male versus female angular comparison
      reflected the differential timing in attainment of adult proportions. The three
      dimensional facial morphometry method allowed the noninvasive evaluation of a
      large sample of nonpatient subjects, leading to the definition of three
      dimensional normative data about facial soft tissues. The method could supplement
      more invasive radiographic evaluations, allowing frequent examinations of
      children and adolescents before and during treatment, as well as in the follow
      up.

PMID- 10077066
TI  - Tissue expansion in the reconstruction of Tessier craniofacial clefts: a series
      of 17 patients.
AB  - Tessier craniofacial clefts are among the most surgically challenging examples of
      craniofacial dysmorphology. These clefts are characterized by hypoplasia of soft
      tissue and skeletal elements throughout the three-dimensional extent of the
      cleft. Whereas bone grafting and craniofacial osteotomies have been successful
      toward correcting the underlying skeletal abnormalities, the ultimate success of
      these reconstructions has been limited by the deficiency of skin and soft tissue.
      This deficiency demands reconstruction ideally with tissue of like texture,
      consistency, and, especially in the face, color. Craniofacial tissue expansion
      was used toward reconstructing these facial clefts with like-quality tissue,
      allowing for tension-free reconstruction after osteotomy and bone grafting.
      Seventeen patients with Tessier craniofacial clefts underwent preoperative
      craniofacial soft-tissue expansion in the surgical management of their clefts.
      Tissue expansion was used in the primary correction of facial clefts in eight
      patients, with nine patients undergoing expansion before secondary surgery. In
      this series, tissue expansion has evolved as an important element in overcoming
      the skin and soft-tissue deficiency associated with these clefts, allowing for
      tension-free closure and improved aesthetic results in these surgically
      challenging patients.

PMID- 10077067
TI  - Mechanisms of extraocular muscle injury in orbital fractures.
AB  - The gross and microscopic events that occur after orbital blowout fractures were
      evaluated to assess the mechanisms of diplopia and muscle injury. Intramuscular
      and intraorbital pressures were evaluated in experimental animals, in cadavers,
      and at the time of orbital fracture explorations for repair of orbital fractures
      in humans. Histologic and circulatory changes, muscle pressure recordings, and
      operative observations were evaluated. Creation of a compartment syndrome was
      evaluated to include a histologic evaluation of the orbital fibrous sheath
      network for the extraocular muscles and the intramuscular vasculature. These
      experiments and observations do not support the role of a compartment syndrome in
      ocular motility disturbances because (1) intramuscular pressures were subcritical
      in both humans and animals; (2) no limiting fascial compartment could be
      demonstrated; and (3) microangiograms and histologic evaluations did not confirm
      areas of compartmental ischemic necrosis. Muscle contusion, scarring within and
      around the orbital fibrous sheath network, nerve contusion, and incarceration
      within fractures remain the probable causes of diplopia, with the most likely
      explanations being muscle contusion and fibrosis or incarceration involving the
      muscular fascial network.

PMID- 10077068
TI  - Strain-related bone remodeling in distraction osteogenesis of the mandible.
AB  - Distraction osteogenesis has become a mainstay in craniofacial surgery. However,
      there are several unresolved problems concerning the biology of bone
      regeneration. We investigated the biomechanical effects of mandibular lengthening
      in 32 rabbits on a cellular and histologic level. The mandible was subjected to a
      corticotomy, held in a neutral position for 4 days, and then lengthened at
      various strain rates and frequencies for 10 days. Radiographic, histologic, and
      electron microscopic examinations showed a strain-related bone regeneration.
      Application of physiologic strain rates (2000 microstrains or 0.2 percent) led to
      a bridging of the artificial fracture exhibiting woven ossification, whereas at
      20,000 microstrains trabecular bone formation was demonstrated. In contrast,
      hyperphysiologic strain magnitudes (200,000 microstrains and 300,000
      microstrains) showed a fibrous tissue formation. Multiple strain applications (10
      cycles/day versus 1 cycle/day) increased the width of the distraction gap without
      changing the stage of bone regeneration. The gradual distraction of bone in
      physiologic magnitudes at higher frequencies seems to be desirable for a bony
      differentiation and may help to improve clinical applications.

PMID- 10077069
TI  - Flap prefabrication in the head and neck: a 10-year experience.
AB  - Tissue neovascularized by implanting a vascular pedicle can be transferred as a
      "prefabricated flap" based on the blood flow through the implanted pedicle. This
      technique potentially allows any defined tissue volume to be transferred to any
      specified recipient site, greatly expanding the armamentarium of reconstructive
      options. During the past 10 years, 17 flaps were prefabricated and 15 flaps were
      transferred successfully in 12 patients. Tissue expanders were used as an aid in
      11 flaps. Seven flaps were prefabricated at a distant site and later transferred
      using microsurgical techniques. Ten flaps were prefabricated near the recipient
      site by either transposition of a local vascular pedicle or the microvascular
      transfer of a distant vascular pedicle. The prefabricated flaps were subsequently
      transferred as island pedicle flaps. These local vascular pedicles can be re-used
      to transfer additional neovascularized tissues. Common pedicles used for
      neovascularization included the descending branch of the lateral femoral
      circumflex, superficial temporal, radial, and thoracodorsal pedicles. Most flaps
      developed transient venous congestion that resolved in 36 to 48 hours. Venous
      congestion could be reduced by incorporating a native superficial vein into the
      design of the flap or by extending the prefabrication time from 6 weeks to
      several months. Placing a Gore-Tex sleeve around the proximal pedicle allowed for
      much easier pedicle dissection at the time of transfer. Prefabricated flaps allow
      the transfer of moderate-sized units of thin tissue to recipient sites throughout
      the body. They have been particularly useful in patients recovering from
      extensive burn injury on whom thin donor sites are limited.

PMID- 10077070
TI  - Neuromucosal prelaminated flaps for reconstruction of intraoral lining defects
      after radical tumor resection.
AB  - To reconstruct intraoral lining defects after radical tumor resection by
      reinnervated vascularized mucosa, eight distal radial forearm flaps and two
      fibula flaps were prelaminated. Prelamination was performed by exposing the
      vascularized fascia, onto which the split distal end of a sural graft was fixed.
      The fascia and the sural nerve graft were covered by device-meshed mucosa or
      small full-thickness mucosa pieces. These structures again were covered by a
      Silastic sheet as large as the future flap, and the wound was closed by the
      elevated skin and subcutaneous tissue. Coverage by a Silastic sheet enabled
      mucosal spreading on the fascia, and the final flaps were thin, mucus-producing,
      and larger than the originally inserted mucosa. The 10 neuromucosal prelaminated
      flaps were harvested together with the inserted sural nerve graft after 8 to 10
      weeks. During this time, the patient underwent radiotherapy and chemotherapy.
      Donor sites were closed directly by the preserved skin and subcutaneous tissue.
      Intraoral defects were reconstructed successfully by eight neuromucosal
      prelaminated distal radial forearm flaps and two neuromucosal prelaminated fibula
      flaps. The sural nerve grafts, inserted between the fascia and the mucosa, were
      coaptated eight times with the lingual nerve and two times with the inferior
      alveolar nerve. Intended reinnervation of the mucosa could already be proved
      clinically and histologically in the first two patients after 11 and 9 months.
      Preservation of skin and subcutaneous tissue considerably lowered donor-site
      morbidity. Neuromucosal prelamination enables reconstruction of intraoral lining
      defects by reinnervated mucus-producing tissue. Reconstruction of other mucosa
      lined structures by this method seems feasible. Avoidance of skin islands for
      reconstruction lowers donor-site morbidity.

PMID- 10077071
TI  - Microsurgical reconstruction in recurrent oral cancer: use of a second free flap
      in the same patient.
AB  - Primary microsurgical reconstruction is the treatment of choice for ablative
      defects of oral carcinoma. As a result of this trend, more and more patients with
      recurrent oral carcinoma who have been initially treated with surgical excision
      and reconstructed with free flaps are being seen. However, a second microsurgical
      reconstruction attempt in these cases raises questions about the flap choices,
      availability of recipient vessels, and effects of previous treatment modalities.
      Herein, 35 patients with perioral carcinoma who had two successive tumor
      resections and reconstruction with free flaps on each occasion are presented. A
      total of 75 free tissue transfers were carried out for the first and second
      reconstructions. After the first tumor resection, 28 radial forearm
      fasciocutaneous flaps, 7 fibula osteoseptocutaneous flaps, 1 iliac
      osteomyocutaneous flap, and 2 rectus abdominis myocutaneous flaps were used. For
      reconstruction after the recurrence, 17 radial forearm fasciocutaneous flaps, 13
      fibula osteoseptocutaneous flaps, 3 rectus abdominis myocutaneous flaps, 2
      anterolateral thigh flaps, 1 jejunum flap, and 1 tensor fasciae latae flap were
      used. More vascularized bone transfers were performed during the second
      reconstruction since the excision for the recurrence frequently required
      segmental mandibulectomy. The complete flap survival rate was 97.3 percent and
      94.6 percent with a reexploration rate of 7.9 percent and 13.5 percent for the
      first and second free tissue transfers, respectively. The mean follow-up time
      throughout the procedures was 37.5 months. Disease-free interval between
      reconstructions was 20.8 months. At the time of evaluation, 54.3 percent of the
      patients were surviving an average of 19 months since the second reconstruction.
      The results suggest that free flaps represent an important option in
      reconstruction of recurrent perioral carcinoma cases undergoing reexcision. When
      used in this indication they are as safe and effective as the initial procedure.

PMID- 10077072
TI  - Free fibula osteoseptocutaneous-pedicled pectoralis major myocutaneous flap
      combination in reconstruction of extensive composite mandibular defects.
AB  - Lateral composite mandibular defects resulting from excision of advanced oral
      carcinoma often require mandible, intra-oral lining, external face, and soft
      tissue bulk reconstruction. Ignorance of importance soft-tissue deficit in those
      patients may cause significant morbidity and functional loss. Such defects,
      therefore, can be reconstructed best with a double free flap technique. However,
      this procedure may not be feasible for every patient or surgeon. An alternative
      procedure is a free fibula osteoseptocutaneous flap combined with a pedicled
      pectoralis major myocutaneous flap. This combination was used in reconstruction
      of extensive composite mandibular defects in 14 patients with T3/T4 oral squamous
      cell carcinoma. All patients were men, and the average age was 54.3 years. The
      septocutaneous paddle of the fibula flap was used for the mucosal lining of the
      defects while the bony part established the rigid mandibular continuity. The
      pectoralis major flap then covered the external skin defect in the face and
      cheek, and the dead spaces left by the extirpated masticator muscles, buccal fat,
      and parotid gland. One free fibula flap failed totally, and one pectoralis major
      flap developed marginal necrosis. At the time of final evaluation, nine patients
      (64.3 percent) were alive, surviving an average of 25.7 months. All patients
      eventually regained their oral continence and an acceptable cosmetic appearance.
      In conclusion, the fibula osteoseptocutaneous flap plus regional myocutaneous
      flap choice is a successful and technically less demanding alternative to the
      double free flap procedures in reconstruction of extensive lateral mandibular
      defects.

PMID- 10077073
TI  - Reliability of the proximal skin paddle of the osteocutaneous free fibula flap: a
      prospective clinical study.
AB  - The vascularization of the skin paddle of 20 osteocutaneous fibula free flaps in
      20 patients was studied. All skin paddles were designed over the proximal and
      middle third of the fibula. A parallel vascularization of the skin was found in
      10 cases. In these cases, an axial (septo)musculocutaneous perforator was found
      to originate high in the peroneal artery or even in the popliteal artery. This
      branch runs parallel to the peroneal artery without any further connections with
      it. In 5 of these 10 cases, no other skin perforators were located within the
      boundaries of the skin paddle. Harvesting such a flap in the traditional way by
      blind inclusion of a muscle cuff results in ligation of the supplying vessel of
      the skin paddle and subsequent loss of the skin. In this series, this would have
      been the case in 5 of the 20 patients (25 percent). This might explain the bad
      reputation of the skin paddle of this flap. The high prevalence of the described
      vascular configuration in a proximally designed skin paddle justifies a vue
      dissection of all musculocutaneous perforators up to their origin, unless one or
      more septocutaneous perforators are found within the boundaries of the flap.

PMID- 10077074
TI  - Functional reconstruction using a depressor anguli oris musculocutaneous flap for
      large lower lip defects, especially for elderly patients.
AB  - Described here is a new technique to reconstruct large lower lip defects using
      one or two musculocutaneous island flaps, which includes an innervated depressor
      anguli oris muscle and has a facial artery in its pedicle. Vermilion is
      simultaneously reconstructed using a mucosal transposition flap. Three patients
      who had a total lower lip defect and five patients who had a defect larger than
      one-half of the lower lip were treated by our procedure. All the flaps survived
      completely without any signs of vascular stasis. In six patients, sphincter
      function and sensation appeared within 3 months after surgery. In one patient who
      needed a total lower lip reconstruction, the depressor anguli oris muscle was
      atrophic and the motor nerve could not be found. This patient could not regain
      motion. One other patient complained of a sialorrhea accompanied by sensory loss;
      however, his sensation improved within 6 months after surgery. All of the
      reconstructed lower lips were large enough to enable the patient to wear dentures
      and were of a cosmetically acceptable appearance 1 year after surgery.

PMID- 10077075
TI  - Reestablishment of sensitivity in the latissimus dorsi transplant through
      anastomosis of the thoracodorsal nerve with sensitive nerves.
AB  - The question as to whether anastomosis of sensory nerves is recommended for free
      transplants of the myocutaneous latissimus dorsi flap, reanastomosed by
      microvascular surgery, remains a controversial issue. In this study, a
      microsurgical nerve anastomosis was performed to sensitize a latissimus dorsi
      transplant. To determine sensation in the transplanted tissue, six patients were
      examined clinically. All patients had free transplants of latissimus dorsi flaps
      reanastomosed by microvascular surgery after tumor resection in the oral cavity.
      An anastomosis of the sensible auricular magnus nerve with the motor
      thoracodorsalis nerve was performed. Resulting sensation was determined
      clinically by testing for pain, temperature, pressure, two-point discrimination,
      and vibration. All patients showed sensation in the latissimus dorsi flap
      beginning between the third and the fifth month postoperatively. Therefore,
      resensitization of a large and voluminous myocutaneous latissimus dorsi flap
      should be attempted by a nerve anastomosis in this transplant.

PMID- 10077076
TI  - Arch reduction mammaplasty.
AB  - Arch mammaplasty is a breast reduction technique based on the inferior pedicle.
      It uses all the specific advantages of the inferior pedicle while avoiding the
      inframammary scars and dead space that occur with the inverted T technique. Arch
      mammaplasty has proven versatile and extremely safe, and it has a surprisingly
      good rate of acceptance by the patients. The scarring is aesthetically superior
      to that obtained with the well-accepted, inverted-T scar technique of the past.

PMID- 10077077
TI  - Reliability of inferior pedicle reduction mammaplasty in burned oversized
      breasts.
AB  - Heavy pendulous breasts cause physical and psychological trauma. Postburn
      deformity of breasts results in significant asymmetry, displacement of nipple
      areola complex, due to burn scar contracture, and significant scarring; these
      factors add more psychological discomfort and subsequent behavioral changes. The
      use of the inferior pedicle procedure in burned breasts can solve many problems.
      The technique reduces the size of the large breast, eliminates the scar tissue by
      excising both medial and lateral flaps, and brings the mal-located nipple and
      areola to a normal position. This study stresses the possibility of harvesting
      the inferior dermal pedicle flap from within the postburn scar tissue without
      necrosis of the nipple and areola, because of the excellent flap circulation.
      Acceptable aesthetic appearance and retainment of nipple viability and
      sensitivity can be achieved with the inferior pedicle technique even with
      postburn deformity of the breast. The study was conducted on 11 women, all of
      whom had sustained deep thermal burns to the breasts and anterior torso and whose
      breasts were hypertrophied and pendulous.

PMID- 10077078
TI  - Improving safety and aesthetic results in inverted T scar breast reduction.
AB  - Breast reduction using an inverted T scar skin design and a variety of glandular
      pedicle types is widely practiced and is the standard by which more recent
      limited scar techniques are judged. The inverted T procedures are attractive
      because they are predictable and versatile and permit great control over both the
      extent of reduction and the breast-shaping process. Despite these advantages,
      common criticisms of inverted T scar techniques include breast shape
      abnormalities, areolar malposition, hypertrophic scars, and poor long-term
      projection. Preoperative markings influence both safety and aesthetics. A method
      of skin marking that is based on a displacement method to determine vertical limb
      splay angle is described. This design concept must be modified to address certain
      variants, such as macromastia presenting with normal nipple position or large
      diameter areolae, moderately severe macromastia, and macromastia involving
      radiated breasts. Safety in breast reduction is improved by paying attention to
      patient positioning issues, using techniques that minimize blood loss, raising
      flaps of appropriate thickness in the correct plane, and performing resection by
      observing the principles that reduce the risk of compromise of nipple and areolar
      circulation. Aesthetic results are improved by analyzing vertical breast meridian
      lengths during final breast shaping, modifying areolar shape as necessary, and
      carefully tailoring the medial inframammary crease. The latter is also important
      for minimizing the potential for scar hypertrophy. The principles presented have
      been refined during the course of a 12-year experience with several hundred
      breast reduction procedures. They contribute to improved results in inverted T
      scar breast reduction when practiced consistently.

PMID- 10077079
TI  - Short scar periareolar inferior pedicle reduction (SPAIR) mammaplasty.
AB  - A method of breast reduction is presented that maintains the blood supply and
      innervation to the nipple and areola complex by means of an inferior pedicle,
      reduces the breast volume by removing tissue from the periphery of the breast,
      maintains breast shape with internal plication sutures, and limits the scar using
      a periareolar technique with a short inferior vertical-to-oblique extension.
      There were 167 breasts in 98 patients reduced in this fashion. The average
      resection volume was 632 g per breast, with an average follow-up of 7.6 months.
      The complication rate was similar to that observed using traditional inferior
      pedicle techniques with the inverted-T cutaneous scar. This technique has proven
      to be versatile, technically straightforward, and applicable to breasts of all
      sizes for both breast reduction and mastopexy. By combining the aesthetic
      advantage of less cutaneous scarring with the safety and familiarity of the
      inferiorly based pedicle, superior results in breast reduction can be obtained
      that are consistent, long-lasting, and satisfying for both patient and surgeon
      alike.

PMID- 10077080
TI  - A new classification for the standardization of nomenclature in free flap wound
      closure.
AB  - A profusion of terms are currently used to describe free flap wound closure. It
      is important to broadly standardize nomenclature when embarking on a comparison
      of functional outcomes between institutions. Therefore, a series of 68
      "emergency" (within 24 hours) free flaps performed by a single surgeon were
      reviewed with respect to a total experience of 188 free tissue transfers to
      formulate a consistent nomenclature applicable to free flap wound closure in
      general. The nomenclature presented divides free flap closure into three
      categories: "primary free flap closure" (12 to 24 hours), "delayed primary free
      flap closure" (2 to 7 days), and "secondary free flap closure" (after 7 days).
      This system is analogous to the standard terms "primary," "delayed primary," and
      "secondary wound closure." It is consistent with known biologic and microbiologic
      principles of wound closure in general and should provide a simple basis for
      classifying free flap wound closure. Illustrative examples are presented to
      highlight the classification scheme.

PMID- 10077081
TI  - Free groin flap revisited.
AB  - Reported herein are 130 consecutive cases of free groin flap transfer performed
      by one surgeon over a 19-year period. Transplantation was performed for soft
      tissue cover or augmentation of contour defects involving the head and neck (68
      cases), trunk (4 cases), upper limb (14 cases), and lower limb (44 cases).
      Indications for flap coverage/augmentation were classified broadly into tumor,
      trauma, radiation induced, and miscellaneous. Specific reconstructive problems
      included augmentation for Romberg's hemifacial atrophy, external ear canal
      reconstruction after tumor ablation, and coverage of lower limb defects. There
      were nine failures (total flap loss), seven cases of partial flap loss, and two
      cases were abandoned intraoperatively. Of 15 cases that were urgently re
      explored, 9 flaps were salvaged. The failure rate for the groin flap series (130
      cases) was 8.5 percent compared with the failure rate of 4.2 percent for the
      other 517 cases of microvascular transfer performed over the same period by the
      same surgeon. Donor-site complications occurred in 24 cases and included hematoma
      or seroma formation, hypertrophic scars, nerve paresthesiae, infection, and
      dehiscence. Secondary debulking procedures were performed in 26 cases. The free
      groin flap, contrary to some reports, is a reliable flap that provides relatively
      thin pliable soft-tissue cover or augmentation, with minimal donor-site
      morbidity. The specific indications for its use have undergone an evolution since
      first described in 1973.

PMID- 10077082
TI  - Reconstruction of soft-tissue defects using serratus anterior adipofascial free
      flap.
AB  - The serratus anterior muscle has been suggested as a versatile and reliable flap
      for reconstruction of head and neck and extremity injuries. The adipofascial
      layer overlying the serratus anterior muscle is the anatomic layer, which is
      supplied by the same branch of thoracodorsal artery. Even though great progress
      has occurred in the prevention of postoperative adhesion of extremity injuries,
      the problem has not been completely solved and is still of special importance in
      complex injuries. Between March of 1995 and February of 1996, seven patients
      underwent reconstructive operation as a result of soft-tissue defects of the
      upper or lower extremities or the scalp. We transferred free adipofascial tissue
      overlying the serratus anterior muscle in three patients and both serratus
      anterior muscle and adipofascial tissue in four patients. A free adipofascial
      flap overlying serratus anterior muscle was transferred when a gliding surface
      was required, owing to the exposure of tendons and neurovascular structures. The
      average duration from operation to follow-up examination was 8 months (from 4 to
      16 months). The results of the operations were satisfactory in functional and
      cosmetic aspects. This kind of flap was very effective in reconstruction of soft
      tissue defects and gliding surfaces for these reasons: easy dissection, the
      capability of obtaining a long vascular pedicle, large-sized flap, composite flap
      including muscle or rib, and the fact that there was no serious functional or
      cosmetic deficit at the donor site.

PMID- 10077083
TI  - Split flexor carpi radialis muscle.
AB  - A detailed anatomic and intramuscular neural staining study in 22 human and 5
      monkey upper limbs revealed that the flexor carpi radialis can be raised on its
      proximal neurovascular pedicle and that the muscle can be split along its tendon
      into two independently functioning neuromuscular compartments, each with its own
      nerve and blood supply. A study of the muscle architecture in the human specimens
      found the radial compartment to have significantly longer fiber length and a
      larger physiologic cross-sectional area than the ulnar compartment. Independence
      of function of each compartment was demonstrated in electrical stimulation
      studies in six monkeys (Macaca fascicularis), but no significant difference was
      noted in the peak isometric load between the two compartments (p = 0.68) in the
      monkey. The extra functioning muscle units become important in local transfers
      for restoring function in multiple nerve palsies as in Hansen's disease, severe
      traumatic loss of muscle in crush injuries and compartment syndromes, and after
      wide resection in infective and neoplastic conditions in the forearm and hand.

PMID- 10077084
TI  - Effects of L-NAME and L-arginine on ischemia-reperfusion injury in rat skeletal
      muscle.
AB  - The involvement of nitric oxide in ischemia-reperfusion injury remains
      controversial and has been reported to be both beneficial and deleterious,
      depending on the tissue and model used. This study evaluated the effects of the
      nitric oxide synthase inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) and
      the substrate for nitric oxide synthase, L-arginine on skeletal muscle necrosis
      in a rat model of ischemia-reperfusion injury. The rectus femoris muscle in male
      Wistar rats (250 to 500 g) was isolated on its vascular pedicle and subjected to
      4 hours of complete arteriovenous occlusion. The animals were divided into five
      groups: (1) sham-raised control, no ischemia, no treatment (n = 6); (2) 4 hours
      of ischemia (n = 6); (3) vehicle control, 4 hours of ischemia + saline (n = 6);
      (4) 4 hours of ischemia + L-arginine infusion (n = 6); and (5) 4 hours of
      ischemia + L-NAME infusion (n = 6). The infusions (10 mg/kg) were administered
      into the contralateral femoral vein beginning 5 minutes before reperfusion and
      during the following 30 to 45 minutes. Upon reperfusion, the muscle was sutured
      in its anatomic position and all wounds were closed. The percentage of muscle
      necrosis was assessed after 24 hours of reperfusion by serial transections,
      nitroblue tetrazolium staining, digital photography, and computerized planimetry.
      Sham (group 1) animals sustained baseline necrosis of 11.9 +/- 3.0 (percentage
      necrosis +/- SEM). Four hours of ischemia (group 2) significantly increased
      necrosis to 79.2 +/- 1.4 (p < 0.01). Vehicle control (group 3) had no significant
      difference in necrosis (81.17 +/- 5.0) versus untreated animals subjected to 4
      hours of ischemia (group 2). Animals treated with L-arginine (group 4) had
      significantly reduced necrosis to 34.6 +/- 7.5 versus untreated (group 2) animals
      (p < 0.01). Animals infused with L-NAME (group 5) had no significant difference
      in necrosis (68.2 +/- 6.7) versus untreated (group 2) animals. L-Arginine (nitric
      oxide donor) significantly decreased the severity of muscle necrosis in this rat
      model of ischemia-reperfusion injury. L-arginine is known to increase the amount
      of nitric oxide through the action of nitric oxide synthase, whereas L-NAME,
      known to inhibit nitric oxide synthase and decrease nitric oxide production, had
      comparable results to the untreated 4-hour ischemia group. These results suggest
      that L-arginine, presumably through nitric oxide mediation, appears beneficial to
      rat skeletal muscle subjected to ischemia-reperfusion injury.

PMID- 10077085
TI  - Coadministration of basic fibroblast growth factor and sucrose octasulfate
      (sucralfate) facilitates the rat dorsal flap survival and viability.
AB  - The effective use of local growth factors and cytokines may replace the lengthy
      staged surgical delay process. We tested the efficacy of basic fibroblast growth
      factor (bFGF) coadministered with sucralfate (sucrose octasulfate) on the rat
      dorsal flap model. A total of 76 male Wistar rats were used in this experiment.
      Four groups of the animals were divided. Group 1 (n = 5) was the vehicle control
      (saline soaked), group 2 (n = 5) was sucrose octasulfate soaked (100 microg/ml, 1
      ml), group 3 (n = 5) was bFGF soaked (1 microg/ml, 1 ml), and group 4 (n = 5) was
      both bFGF and sucrose octasulfate soaked. All agents were soaked equally in
      Gelfoam. The flap survival measured by the quantitative computer-assisted
      morphologic analysis was significantly improved by day 5 postoperatively in the
      combined administration group compared with the vehicle control (81 and 53
      percent, respectively; p < 0.05). In lead oxide-gelatin microangiography, there
      was enhanced pedicle vessel formation observed as well as the extended vessel
      sprouting up to very close to the distal end in combined group on day 5. The
      endogenous bFGF mRNA expressions shown by reverse transcriptase-polymerase chain
      reaction were detected in all four groups. The angiogenesis indicated by alpha
      smooth muscle actin immunopositivity was significantly more enhanced in the
      combined group than the vehicle control (37.3 and 19.4, respectively; p < 0.01).
      In the combined group, there was stronger immunopositivity for bFGF in epidermis
      and hair follicles observed, and more notably bFGF-immunopositive dermal
      fibroblasts were evident. Thus, coadministration of bFGF and sucralfate markedly
      facilitates the rat dorsal flap survivability by enhancing the bFGF expression
      and angiogenesis.

PMID- 10077086
TI  - Familial gigantiform cementoma.
AB  - Familial gigantiform cementoma is a rare autosomal dominant tumor that is benign
      but can result in disfigurement of the facial skeleton. Two families with a total
      of five patients presented for treatment. Because of a lack of opportunity to
      obtain treatment early, three of the patients presented in adult life with
      massive tumors requiring extensive resection and complex reconstruction in
      multiple stages. The two female patients had chronic anemia caused by multifocal
      polypoid adenomas of the uterus and required hysterectomy before treatment. The
      last three patients had elevated alkaline phosphatase levels before tumor
      resection, and these levels decreased after surgery. With extensive resection of
      the tumors and reconstruction of both the soft tissues and facial skeleton, good
      functional and aesthetic results can be obtained. There has been no tumor
      recurrence with 3 years of follow-up.

PMID- 10077087
TI  - A new transfacial approach for lesions of the clivus and parapharyngeal space:
      the partial segmented Le Fort I osteotomy.
AB  - Tumors of the clival and parapharyngeal areas are a challenge because of their
      location. They used to be considered inaccessible because the aggressive
      approaches employed caused elevated levels of morbidity. This fact led to more
      conservative approaches that attempted to preserve the exposure of the lesion.
      These approaches were a combination of cranial and facial procedures, thus
      utilizing a combined effort between neurosurgeons and maxillofacial surgeons. We
      described our experience with a partial segmented Le Fort I osteotomy added to a
      transmandibular approach to expose a chordoma of the clivus and left
      parapharyngeal space. A three-dimensional imaging was used as a diagnostic tool
      and to plan the optimal surgical approach. The operative technique was described
      in this case study. Some important technical details of the approach are
      described. The global outcome was favorable.

PMID- 10077088
TI  - Lower back coverage with endoscopically harvested pedicled greater omental flap.
AB  - An alternative surgical treatment is proposed here for radionecrosis of the lower
      back. A 78-year-old patient was treated successfully for a nonhealing ulcer with
      a pedicled omental flap. The omentum was harvested endoscopically and brought out
      of abdominal cavity through a limited incision on lateral left side of abdominal
      wall. The omentum was then tunneled to the back for coverage the lower back. The
      combination of an endoscopic harvest of an omental flap performed by a general
      surgeon and wound debridement and skin grafting of the omentum by a plastic
      surgeon allows minimal donor-site morbidity and avoids the use of delicate
      microsurgical technique. Additionally, omentum is an ideal flap for the treatment
      of radionecrosis.

PMID- 10077089
TI  - Free vascularized appendix transfer for reconstruction of penile urethras with
      severe fibrosis.
AB  - Despite the development of newer techniques with a free radial forearm tube flaps
      for phallus reconstruction, severe urethral strictures are still seen in such
      cases after irradiation or repeated infection because of the paucity of healthy,
      well-vascularized tissue. For urethral reconstruction in cases with poorly
      vascularized tissue as well as for total penile creation, a new technique
      involving a free vascularized appendix transfer combined with a radial forearm
      osteocutaneous flap was successfully used in two cases. The appendix provides a
      normal tube structure composed of a muscular tubular layer lined with mucosal
      epithelium. It has no hair and has rich vascularization. This results in little
      stricture at the junction with the original urethra, no occurrence of urethral
      stones, and possible postoperative enlargement of the diameter with changes in
      catheters. This method will allow a patient with severe fibrosis around the
      urethra to undergo one-stage phallus reconstruction with minimal complications.

PMID- 10077090
TI  - Endoscopically assisted facial suspension for treatment of facial palsy.
AB  - Static suspension remains an option for certain patients with facial paralysis.
      Endoscopically assisted facial suspension obviates the need for a counter
      incision at the oral commissure to distally inset the fascia lata graft as
      described in the standard technique. The endoscopic technique is simple, allows
      secure placement of perioral fascial strips, and can be performed as an
      outpatient.

PMID- 10077091
TI  - A simple negative suction drain for ear reconstruction.

PMID- 10077092
TI  - External mastopexy with imbrication following explantation.
AB  - The external mastopexy with inferior pull invagination is indicated in patients
      with grade II ptosis or greater and breast parenchyma less than 200 cc. Based on
      our experience with nine patients, the advantage of this technique is better
      inferior support with projection to the breast secondary to the imbrication.

PMID- 10077093
TI  - Clinical application of free digital artery flap of the hand.

PMID- 10077094
TI  - The effects of ultrasonic energy on peripheral nerves: implications for
      ultrasound-assisted liposuction.
AB  - The integration of ultrasound-assisted liposuction with traditional suction
      assisted lipoplasty has extended the role of liposuction in body contouring.
      Although there are ample data regarding the effects of ultrasound on peripheral
      nerves from studies with the Cavitron ultrasound surgical aspirator, there is
      little information concerning the effects of modern ultrasound body contouring
      equipment on neural tissue. This study was designed to evaluate the functional
      and histologic effects of ultrasound energy on rat peripheral nerves (sciatic
      nerves) using a commonly-used ultrasound-assisted liposuction generator. After
      the application of ultrasound to exposed rat sciatic nerves, operative
      magnification was used to assess any visible injury. The sciatic function index
      was serially measured to quantify immediate and long-term functional effects on
      the nerves. Our results showed immediate visible injury using low amplitude
      settings (level 6), but no functional evidence of injury until much higher
      settings were used (level 9). All animals in the groups with initial functional
      impairment had returned to normal or near-normal function at completion of the
      study (51 days). Histologic examination revealed no evidence of damage in the low
      amplitude groups. Histologic analysis of the high amplitude groups displayed
      diffuse infiltration of the nerve, with foamy histiocytes and an increased number
      of mast cells, consistent with remote neural injury followed by myelin breakdown
      and repair.

PMID- 10077095
TI  - The tumescent technique: the effect of high tissue pressure and dilute
      epinephrine on absorption of lidocaine.
AB  - Injection of lidocaine into the subcutaneous tissues by the tumescent technique
      results in a delayed absorption of the local anesthetic and has allowed
      clinicians to exceed the maximum recommended dose of lidocaine without reported
      complications. However, little knowledge exists about the mechanisms that permit
      such high doses of lidocaine to be used safely with this technique. The presence
      of low concentration epinephrine and the increased tissue pressure resulting from
      the tumescent injection have both been implicated as important factors, but
      neither has been studied in patients whose results were not altered by the
      variability of the suction procedure. The purpose of this work was to determine
      the effect of tissue pressure during tumescent injection and presence of low
      concentration epinephrine on the absorption of lidocaine from subcutaneous
      tissues in human volunteers. Twenty healthy female human volunteers were
      randomized into four study groups. After body fat measurements, all subjects
      received an injection of 7 mg/kg of lidocaine into the subcutaneous tissues of
      both lateral thighs. The injected solution consisted of 0.1% lidocaine and 12.5
      meq/liter sodium bicarbonate in normal saline with or without 1:1,000,000
      epinephrine. Tissue pressure was recorded during injection using a specially
      designed double-barreled needle. The time required for injection was also
      recorded. Subjects in group 1 received lidocaine with epinephrine injected by a
      high-pressure technique. Group 2 subjects received lidocaine with epinephrine
      injected by a low-pressure technique. Group 3 subjects received lidocaine without
      epinephrine injected under high pressure. Group 4 subjects received lidocaine
      without epinephrine injected under low pressure. Following injection, sequential
      blood samples were drawn over a 14-hour period, and plasma lidocaine
      concentrations were determined by gas chromatography. No suction lipectomy was
      performed. Maximum tissue pressure during injection was 339 +/- 63 mmHg and 27 +/
      9 mmHg using high- and low-pressure techniques, respectively. Addition of
      1:1,000,000 epinephrine, regardless of the pressure of injected fluid,
      significantly delayed the time to peak plasma concentration by over 7 hours.
      There was no significant difference in the peak plasma concentration of lidocaine
      among the four groups. Peak plasma concentrations greater than 1 mcg/ml were seen
      in 11 subjects. Epinephrine (1:1,000,000) significantly delays the absorption of
      lidocaine administered by the tumescent technique. High pressure generated in the
      subcutaneous tissues during injection of the solution does not affect lidocaine
      absorption. The delay in absorption may allow time for some lidocaine to be
      removed from the tissues by suction lipectomy. In addition, the slow rise to peak
      lidocaine concentration in the epinephrine groups may allow the development of
      systemic tolerance to high lidocaine plasma levels.

PMID- 10077096
TI  - Use of cartilaginous autografts in nasal surgery: 8 years of experience.
AB  - Although the cartilaginous autografts are one of the tissues more utilized in
      nasal surgery, a comparative study does not exist to determine which are better
      options and their precise indications. It is for this reason that a
      histopathologic analysis was carried out comparing the characteristics and
      properties of the four principal cartilages that are utilized in aesthetic
      functional surgery of the nose. Considering these particularities, the precise
      indications for the employment of the different cartilage as nasal autografts
      were determined. Of 1120 aesthetic functional rhinoplasties during a period of 8
      years, 930 (83 percent) required cartilaginous autografts, 86 percent were
      primary, 11 percent were secondary, and 3 percent had two or more surgeries.
      Eighty-three percent of the grafts used were from nasal septum, 12 percent from
      the auricle, 3 percent from alar cartilages, and 2 percent from the rib. The
      anatomic sites in which they were employed consisted of the following: 64 percent
      between the medial crura, 28 percent as in Sheen's graft, 19 percent in the nasal
      dorsum, 8 percent as spreader grafts, 8 percent as in Peck's graft, and 3 percent
      in the rim to improve alar collapse. We followed at all times the previous
      indications for obtaining and placing the nasal autografts. Eighty-four percent
      of the patients were totally satisfied and only 8 percent required a second
      surgical procedure to achieve the results desired. Based on this study, it is
      recommended to utilize the cartilaginous autografts in nasal surgery considering
      three parameters: the physical and histologic characteristics of each cartilage,
      the anatomic site in which they are to be placed, and the effect desired with
      their application.

PMID- 10077097
TI  - Transconjunctival upper blepharoplasty.
AB  - Transconjunctival lower lid blepharoplasty now has an established role as an
      option in rejuvenation of the lower eyelid. Transconjunctival upper lid
      blepharoplasty, or transconjunctival removal of medial upper eyelid fat, also has
      a role in rejuvenation of the upper eyelid. However, this is a rather limited
      role. We have found this approach safe and efficacious as a primary as well as a
      secondary procedure for removal of excess medial upper eyelid fat. We report on
      20 patients who have undergone this operation: 5 as a primary procedure and 15 as
      secondary. There were no complications, no revisions, and the patients have been
      uniformly happy with their results.

PMID- 10077098
TI  - Marriage abdominoplasty expands the mini-abdominoplasty concept.
AB  - The marriage of aggressive superwet liposculpture of the abdomen and adjacent
      anatomic regions with a modification of well-established open surgical techniques
      to address skin excess and perform muscle plication was used to treat 29 patients
      presenting for aesthetic abdominal contouring over the past 3 1/2 years. The
      charts of 57 patients who had aesthetic contouring procedures on the abdomen
      performed from December of 1994 to July of 1998 were retrospectively reviewed.
      Fifteen patients underwent suction lipectomy alone, 13 patients were treated with
      conventional abdominoplasty, and 29 underwent "marriage abdominoplasty." The 29
      patients who underwent marriage abdominoplasty presented with deformities marked
      by excess lower abdominal skin and adipose tissue, with or without muscle laxity
      (Psillakis types II, III, and IV). Seventeen procedures were performed under
      local anesthesia with deep conscious sedation on an outpatient surgical basis. In
      12 patients, the operation accompanied a hysterectomy, urologic procedure, or
      additional aesthetic surgical procedure(s) and was done under general anesthesia.
      Suction aspirates ranged between 540 and 2600 cc (mean, 1160 cc) and were
      accompanied by lower abdominal skin excision in every case, which was performed
      predominantly through short and medium-length incisions (mean, 15 cm). Rectus
      abdominis muscle plication was performed where necessary, using vertical
      plication of the infraumbilical rectus muscles in 27 patients (93 percent) and
      full-length plication in two patients (7 percent). All patients demonstrated
      significantly improved contours and have seemed to manifest less pain when
      compared with patients treated by full traditional abdominoplasty. Postoperative
      complications have included upper abdominal skin waviness (2), annoying
      paresthesias and discomfort persisting for 6 months (1), seroma (1), and marginal
      skin necrosis with an open wound (1). The latter problem occurred in the only
      patient who was treated with a revision procedure. Thus, the complication rate
      was 17 percent (5 of 29 patients). The marriage of aggressive superwet
      liposculpture of the entire abdomen with standard open surgical techniques used
      to treat skin excesses and allow abdominal muscle plication where necessary
      offers the advantage of reduced surgery when compared with full abdominoplasty,
      while consistently achieving significant contour improvement. This concept is
      applicable to the majority of patients presenting for the treatment of abdominal
      deformities and has markedly expanded the application of the mini-abdominoplasty
      concept.

PMID- 10077099
TI  - The correction of lower lid malposition following lower lid blepharoplasty.

PMID- 10077100
TI  - Expanded applications for transconjunctival lower lid blepharoplasty.

PMID- 10077101
TI  - The neuromuscular compartments of the flexor carpi ulnaris.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Report on the vascular supply and innervation pattern of the flexor carpi
      ulnaris. 2. Describe the muscle architecture of the flexor carpi ulnaris,
      including the physiological cross-sectional area and fiber length. 3. State the
      uses of the flexor carpi ulnaris both for resurfacing defects in the vicinity of
      the elbow and in local functional tendon transfers. 4. Understand the principles
      of splitting skeletal muscles based on neurovascular supply to enhance its
      utilization in reconstructive procedures. The aim of this study was to describe
      the intramuscular innervation and vascular supply of the human flexor carpi
      ulnaris, with confirmation of findings by a similar study in the primate. Two
      distinct intramuscular nerve branches running parallel to each other, on either
      side of a central tendon, from the proximal quarter of the muscle belly to its
      insertion were found. The muscle could then be split into a humeral and an ulnar
      compartment, each with its own primary nerve branch. Perfusion studies confirmed
      the adequacy of circulation to the two compartments. In the primate flexor carpi
      ulnaris, electrical stimulation of the respective branches revealed independent
      contraction of each compartment. This study provides useful information for
      enabling the local transfer of the muscle as a whole, both for resurfacing in the
      vicinity of the elbow and for functional tendon transfers. It will also enable
      the transfer of the muscle as one or two separate compartments (for resurfacing,
      in tendon transfers for muscle paralysis, congenital defects, and muscle defects
      resulting from trauma, and after resections for neoplasm and infection).

PMID- 10077102
TI  - "You guys are on the fringe--aren't you?".

PMID- 10077103
TI  - Lasers in aesthetic plastic surgery: caveat emptor.

PMID- 10077104
TI  - Molecular genetic advances in understanding craniosynostosis.

PMID- 10077105
TI  - An early description of the superficial musculoaponeurotic system by Sir Charles
      Bell.

PMID- 10077106
TI  - What age(s) for face lifts?

PMID- 10077107
TI  - Total face reconstruction: skin graft versus free flap.

PMID- 10077108
TI  - Muller's muscle and eyelid function.

PMID- 10077109
TI  - Palpebral bags.

PMID- 10077110
TI  - A proposed nomenclature for rhytidectomy.

PMID- 10077111
TI  - Nasal packing in rhinoplasty and septorhinoplasty: it is wiser to avoid.

PMID- 10077112
TI  - The retraction of the oral opening in burned patients.

PMID- 10077113
TI  - Cross-lip vermilion "tri-tailed" flap to correct the "whistling lip" deformity.

PMID- 10077114
TI  - The amniotic band syndrome.

PMID- 10077115
TI  - Maxillary distraction.

PMID- 10077116
TI  - A minimally invasive method of harvesting iliac cancellous bone.

PMID- 10077117
TI  - Failure of silicone gel breast implants.

PMID- 10077118
TI  - Skin-sparing total mastectomy.

PMID- 10077119
TI  - Brown pigmentation in the outer lumen of breast implants.

PMID- 10077121
TI  - EQUAM Declaration on Breast Implants, July 4, 1998. European Committee on Quality
      Assurance and Medical Devices in Plastic Surgery.

PMID- 10077120
TI  - Periareolar subcuticular pursestring suture.

PMID- 10077122
TI  - Acute carpal tunnel syndrome: related to the tumescent technique?

PMID- 10077123
TI  - Median nerve compression with tumescent fluid administration.

PMID- 10077124
TI  - Cellulite.

PMID- 10077125
TI  - The reverse digital artery flap.

PMID- 10077127
TI  - Delayed primary skin grafting: revisited.

PMID- 10077126
TI  - A comparison of the effects of reduction in arterial inflow and venous outflow.

PMID- 10077128
TI  - A practical method of experimental tissue expansion.

PMID- 10077129
TI  - Bidirectional armed needle.

PMID- 10077130
TI  - To reduce your seroma rate.

PMID- 10077131
TI  - Vacuum drains.

PMID- 10077132
TI  - Digital transfer and storage of color slides.

PMID- 10077133
TI  - A universal micro-suction mat to optimize TRAM breast reconstruction.

PMID- 10077134
TI  - TRAM flap breast reconstruction in patients with previous abdominal scars.

PMID- 10077135
TI  - Space-obliterating skin suture.

PMID- 10077136
TI  - Herbal interventions in asthma and allergy.
AB  - This paper reviews the role of herbal-based medicines in the treatment of asthma
      and allergic rhinitis. A comprehensive literature search was performed of
      relevant English-language papers and abstracts were identified through a MEDLINE
      search and from bibliographies of the identified papers. Papers and studies
      pertaining to the use of medicinal plants in the treatment of asthma and allergic
      rhinitis were identified. They were then analyzed according to design, inclusion
      and exclusion criteria, population studied, variables tested, method of treatment
      (i.e., specific medicinal plants or herbal combinations), and results. The data
      have been reviewed and divided on the basis of culture and the effects of
      medicinal plants in asthma and allergy. A number of studies were found that
      support the use of some herbal medicines in asthma and allergy. Various
      derivatives from specific medicinal plants were identified as the antiasthma
      components and some mechanisms of action were explored. The results show positive
      effects of these herbs on bronchodilation, pulmonary function tests, and
      antagonism of asthma mediators such as histamine and platelet activating factor,
      corticosteroid levels, and clearance of mucus. Improved symptoms were also seen
      in patients with allergic rhinitis specifically on histamine-induced reactions,
      e.g., rhinorrhea, sneezing, and itching. From the review, there has been a role
      for some herbal medicines in the treatment of asthma and allergic rhinitis. Usage
      of herbal medicines has increased in recent years. Many of these medicinal plants
      provided relief of symptoms equal to allopathic medicines used. Specific chemical
      derivatives have been isolated from many of these plant products which act on the
      mechanisms and mediators that cause asthma and allergies. The amount of research
      on these products, especially in the United States, is limited. There is a lack
      of control of quantity and quality of the components in these remedies. Yet, many
      have fewer side effects than current therapy. Throughout the history of medicine,
      drugs have been developed from traditional medicine. By continuing to investigate
      how some of these herbal interventions work, we may be able to find additional
      effective medicines to treat asthma and allergies.

PMID- 10077137
TI  - Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by
      metered-dose inhaler with InspirEase to relieve acute asthma attack.
AB  - Although the inhalation of beta2-agonists has frequently been used to relieve
      acute asthma attacks, the efficacy of anticholinergic agents for acute asthma
      attacks still remains unclear. This study was designed to compare the inhalation
      of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by
      a metered-dose inhaler with holding chamber (InspirEase) to relieve acute asthma
      attacks. To accomplish this, 69 patients who had presented with an acute asthma
      attack were randomized to receive either fenoterol (1 puff [200 microg/puff]
      every 1 min for 5 min; total 1000 microg) or fenoterol plus oxitropium bromide (2
      puffs [100 microg/puff] every 1 min for 5 min; total 1000 microg). The peak
      expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) values were
      measured before treatment, and 1, 15, 30, and 60 min after the inhalation
      therapy. The ratios of improvement, PEF (or FEV1) after treatment divided by PEF
      (or FEV1) before treatment, were also calculated. Thirty-three patients were
      evaluated in the combination group and 31 patients were evaluated in the
      fenoterol group. The PEF value at 60 min after inhalation therapy of the
      fenoterol plus oxitropium bromide group (261 +/- 18 L/min, mean +/- standard
      error) was significantly higher compared to that of the fenoterol group (210 +/-
      17 L/min). In addition, the ratios of improvement of PEF at 1, 15, 30, and 60 min
      after inhalation therapy were significantly higher in the fenoterol plus
      oxitropium bromide group compared with the fenoterol group.

PMID- 10077138
TI  - The pathogenesis of osteonecrosis and the relationships to corticosteroids.
AB  - One of the challenging issues faced by allergists is a risk-benefit analysis on
      the use of corticosteroids. An uncommon, but serious complication of
      corticosteroids is the development of avascular necrosis (osteonecrosis). In this
      review we present the differential diagnosis and pathophysiology of
      osteonecrosis, with particular emphasis on steroids. Osteonecrosis of the femoral
      head is a common disorder that may be either naturally occurring or iatrogenic.
      With the exception of those cases labeled as idiopathic, the majority are the
      result of some insult to the vascular integrity of the affected hip. The reason
      for this disruption is manifold and can range from direct trauma to the more
      subtle or indirect compromise associated with fatty emboli or often an
      intravascular event such as that seen in sickle cell anemia. Although they are
      not totally understood, corticosteroids present a special problem because of
      susceptibility factors that may make some patients more likely to get
      osteonecrosis than others. The problem may be more complex, in that the
      association between corticosteroid use and osteonecrosis may be disease
      dependent. In any case, any patient receiving long-term corticosteroids should be
      warned of this potentially debilitating complication.

PMID- 10077139
TI  - Comparison of salmeterol with beclomethasone in adult patients with mild
      persistent asthma who are already on low-dose inhaled steroids.
AB  - Current guidelines on asthma management recommend the early use of inhaled
      corticosteroids. Recent studies of patients with moderate to severe asthma show
      that the addition of salmeterol is superior to a further increase of the
      steroids. In this study with adult, mild persistent asthma patients, we compared
      the effects of adding salmeterol 50 microg b.i.d. versus beclomethasone
      dipropionate (BDP) 200 microg b.i.d. (both via Diskhaler dry powder inhaler) to
      the low-dose inhaled steroids. A double-blind, randomized, parallel-group study
      was conducted with a run-in period of 2 weeks and a treatment period of 12 weeks.
      Patients (n = 233) were randomized with a peak expiratory flow (PEF)
      reversibility of 22 +/- 10% (mean +/- SD) in the run-in period. The morning PEF
      was 84 +/- 17% predicted and the age was 42 +/- 14 years (45% males). The average
      prestudy inhaled steroid dose was 361 microg daily. Within a week of salmeterol
      treatment the daily PEF recordings reached maximal levels. At the end of the
      treatment period the evening PEF remained significantly better in the salmeterol
      group than in the BDP group (p = 0.036). The PEFs, measured at the general
      practitioners' (GPs') office, were at least 95% of the predicted values and the
      post-salbutamol values at the end of both treatments. However, the salmeterol
      group had already obtained this level after 2 weeks and differed significantly
      from the beclomethasone group (p = 0.003 for percent predicted and p = 0.0007 for
      post-salbutamol PEF values). The symptom scores and the use of rescue medication
      showed a similar profile. Quality of life improved with both treatments, but
      without significant statistical differences between the groups. The frequency of
      adverse events, typical for beta2-agonists, was low and showed no differences
      between the groups. These results showed that the addition of salmeterol is at
      least as effective as adding beclomethasone in normalizing peak flows and
      improving asthma control in mild persistent asthma patients. Furthermore,
      salmeterol has a much faster onset of action.

PMID- 10077140
TI  - Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to
      hydrofluoroalkane-134a (HFA) albuterol.
AB  - Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and
      use of CFCs, except for certain critical exemptions, has been prohibited by the
      Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is
      still allowed, but the U.S. Food and Drug Administration is planning the
      transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a
      (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol
      (HFA albuterol). This study evaluates whether comparable safety and efficacy
      continues for 12 weeks after patients with asthma are switched from CFC albuterol
      to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12
      week safety and efficacy trial were randomized to either continue receiving CFC
      albuterol or to be switched to receive HFA albuterol in a yearlong safety and
      efficacy trial. Safety and efficacy were compared over the first 12 weeks of the
      yearlong trial between patients who had remained on CFC albuterol and those who
      had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by
      serial spirometry for 6 hr after the patients self-administered the study drug in
      the clinic. Safety was assessed by measuring changes in pulse rate, blood
      pressure, and electrocardiogram (ECG) intervals after dosing with study drug,
      monitoring adverse events, and performing prestudy and poststudy laboratory
      testing and physical examinations. No significant differences in bronchodilator
      efficacy between the patients continuing to receive CFC albuterol and those
      switched to HFA albuterol were found in the 12 weeks after the switch. No
      differences between the two products were found for changes in pulse rate, blood
      pressure, and ECG intervals. Adverse event profiles were similar for the two
      products, except the patients remaining on CFC albuterol reported increased
      asthma symptoms and rhinitis significantly more often than the patients switched
      to HFA albuterol. No clinically meaningful changes in laboratory tests or
      physical examinations were found in either treatment group. Patients with asthma
      switched from CFC albuterol to HFA albuterol receive comparable bronchodilation
      with a similar safety profile as those continuing to receive CFC albuterol.

PMID- 10077141
TI  - Construction and validation of four childhood asthma self-management scales:
      parent barriers, child and parent self-efficacy, and parent belief in treatment
      efficacy.
AB  - This study examined the psychometric properties of four new health belief
      measures for asthmatic children and their parents. A total of 110 asthmatic
      children (aged 7-15) and 129 parents (with asthmatic children aged 3-15)
      responded to a mail-out survey. Evidence for reliability (0.75-0.87) and validity
      was obtained for measures of Parent Barriers to Managing Asthma, Parent Asthma
      Self-Efficacy (subscales: attack prevention and attack management), Parent
      Treatment Efficacy, and Child Asthma Self-Efficacy (subscales: attack prevention
      and attack management). All measures were correlated in the hypothesized
      directions with health status, asthma symptoms, and impact of illness on the
      family.

PMID- 10077142
TI  - Pediatric asthma care in the emergency department: measuring the quality of
      history-taking and discharge planning.
AB  - The National Asthma Education and Prevention Program NAEPP Guidelines include
      recommendations for history-taking and discharge planning during an asthma visit,
      but there are no tools to measure performance. The objectives of this study were
      to define and operationalize key elements of history-taking and discharge
      planning, to develop a tool for measuring these elements, and to evaluate the
      quality of history-taking and discharge planning in the emergency department (ED)
      during visits for asthma using the new tool. Expert opinion and extensive
      literature review were used to develop a 13-item checklist containing items that
      should be documented during history-taking and provided during discharge planning
      for an ED visit for an acute asthma exacerbation by children. A convenience
      sample of 90 pediatric emergency medicine physicians and allergists rated each
      item in the checklist. The checklist was used to score audiotapes of asthma
      visits in the ED. Subjects were 154 parents of asthmatic children aged 4-9 years
      seeking care in nine inner-city EDs affiliated with asthma centers participating
      in the National Cooperative Inner-City Asthma Study and the physician/providers
      who delivered care. Seven of the 13 items on the checklist were rated as required
      to be performed by more than 90% of the allergist/pediatric emergency medicine
      physicians. Only 10% of the 154 visits included all seven of the highly rated
      items, whereas 19% of the visits included three or fewer. Only 7 of the 13 items
      (54%) were performed in more than 50% of the visits, and 4 items were performed
      in fewer than 25% of visits. Based on expert ratings, the checklist for measuring
      elements of history-taking and discharge planning during asthma visits appears to
      have considerable face validity. In the visits studied, the overall performance
      of these elements was low. Interventions to improve performance on the checklist
      might lead to improved care for children with asthma who frequent the ED.

PMID- 10077143
TI  - Microsatellite instability in multiple colorectal tumors.
AB  - Tumor multiplicity is a hallmark of hereditary cancers: in the colon-rectum
      multiple tumors represent 5-10% of all colorectal cancer cases. A portion of
      these cases belongs to hereditary non-polyposis colorectal cancer (HNPCC), a
      genetic cancer syndrome due to mismatch repair (MMR) gene mutations,
      phenotypically expressed as microsatellite instability (MSI); the majority of
      multiple tumors, however, is apparently without any family history. We analyzed
      78 (38 synchronous and 40 metachronous) neoplasms from 37 patients with multiple
      tumors of the large bowel, both HNPCC and sporadic, with the aim of identifying a
      common genetic basis in multiple tumors. DNA was extracted from normal and
      cancerous formalin-fixed tissue and was analyzed for MSI using 6 markers. Tumors
      showing MSI in at least 2 of 6 microsatellite loci were defined as MSI(+). The
      overall number of MSI(+) tumors was 22 (28.2% of the total). A significant
      difference in the rate of MSI(+) between HNPCC and sporadic tumors was observed
      (85% vs. 17%). In the same patients, the MSI phenotype of synchronous tumors
      (both HNPCC and sporadic) tended to be more concordant than that of the
      metachronous ones. The higher frequency of MSI in HNPCC than in sporadic tumors,
      even when multiple, suggests that the involvement of MMR genes in the
      pathogenesis of the sporadic cases may be uncommon, thus confirming that
      screening for MSI in multiple colorectal tumors could be a useful tool in the
      identification of HNPCC in the general population.

PMID- 10077144
TI  - Expression of Epstein-Barr virus lytically related genes in African Burkitt's
      lymphoma: correlation with patient response to therapy.
AB  - A study on the Epstein-Barr virus (EBV)-associated malignancy (endemic) Burkitt's
      lymphoma (BL) was initiated on fine-needle-aspiration biopsies from 46 proven BL
      cases in Malawi. Gene expression that might correlate with patient serology
      (where high levels of antibodies to lytically related genes are commonly
      observed) was explored. In two-thirds of the cases, we identified the EBV BZLF1
      replication activator intermediate early protein ZEBRA in varying quantities and
      to varying extents in cells by immuno-cytochemistry. The early lytic-cycle gene
      transcript BHLF1 was assessed positively by solid-phase hybridisation in over
      half of the same tumours. Evidence of transcription of these genes was confirmed
      on a smaller number of surgically removed fresh biopsies by RT-PCR. We asked
      whether our findings, which are generally counter to the established notion that
      EBV gene expression in BLs is restricted to the latent function, EBNA1, might
      offer some explanation for the differential responses to chemotherapy observed
      among African patients. Where the duration of follow-up was sufficient to assign
      the cases (37 in number) to one of 3 categories, namely, complete, partial or no
      response, a significant correlation between expression of the viral function
      ZEBRA and a positive patient response to treatment was found. Lack of this was
      associated with poor prognosis. Clinical data and EBV gene expression results
      support the postulate of subgroups of African BLs, the intermediate early antigen
      providing a marker of potential use in patient management.

PMID- 10077145
TI  - Familial cancer risks in offspring from discordant parental cancers.
AB  - Analysis of familial cancer risks between discordant sites provides etiologic
      understanding on genetic and environmental risks factors of site-specific
      cancers. We used the Swedish nation-wide Family-Cancer Database to analyze
      familial risks in discordant cancers of offspring and parents. Familial risk
      ratios (FRRs) were calculated for cancer in offspring aged 15 to 53 years at 22
      sites, discordant from parental sites. We confirmed many reported associations.
      Consistent novel findings associated parental-offspring sites of pancreas-breast,
      breast-testis and uterus-nervous system. For these, the FRRs were modest, 1.2 to
      1.5 in the whole Database, but the FRRs increased in those whose parents were
      diagnosed before age 50. Pancreas and liver cancers showed FRRs of 2.5 to 3.3 in
      offspring of women and of 1.3 in offspring of men. One or both of these cancers
      was/were associated with cancers of stomach, colon, breast, uterus, ovary and
      prostate. Melanoma was associated with pancreas, breast, skin and nervous-system
      cancers and with leukemias. Myeloma showed a concordant FRR of about 4.0 and was
      associated with prostate cancer and non-thyroid endocrine-gland cancers.
      Mutations in known cancer-related genes may explain some of these findings, but
      new susceptibility genes are yet to be found. For melanoma, pancreatic and liver
      cancer, environmental factors are important etiologic factors and may contribute
      to the familial effects observed.

PMID- 10077146
TI  - Diet and brain cancer in adults: a case-control study in northeast China.
AB  - A hospital-based case-control study was conducted in the Heilongjiang Province of
      northeast China between May 1993 and May 1995. A total of 129 histologically
      confirmed brain cancer cases (73 gliomas and 56 meningiomas) and 258 matched
      controls were interviewed in 6 major hospitals to examine the influence of
      dietary factors in developing brain cancer. Information was obtained about
      frequency of consumption of 57 food items. Odds ratios (ORs) were obtained from
      conditional logistic regression, including allowance for socio-demographic
      factors, alcohol, tobacco and total energy intake. Consumption of fresh
      vegetables (OR = 0.29 for the highest quartile compared with the lowest one), and
      specifically of Chinese cabbage and onion, fruit (OR = 0.15), fresh fish (OR =
      0.38) and poultry (OR = 0.16) was inversely related to the risk of developing
      brain cancer. A protective effect was also seen for vitamin E intake, calcium
      and, although non-significantly, beta-carotene and vitamin C. Risk of brain
      cancer increased with consumption of salted vegetables (OR = 2.54) and salted
      fish.

PMID- 10077147
TI  - First cytogenetic study of a recurrent familial chordoma of the clivus.
AB  - Two recurrences of a familial clivus chordoma, arisen from a patient who
      developed the primary tumor at age of 8 years, were investigated by cytogenetic
      and the fluorescence in situ hybridization (FISH) approach. Of the patient's 3
      daughters, 2 developed, respectively, a clivus chordoma and an astrocytoma in
      infancy, a familial aggregation highly suggestive of a genetic background. After
      a 31-year hiatus, 2 tumor recurrences, developed over 17 months, were removed
      surgically. Both were hypo- or nearly diploid, and had a pronounced karyotypic
      heterogeneity with clonal and non-clonal rearrangements affecting several
      chromosomes. The same rearrangement, a dic(1;9)(p36.1;p21), was shared in both
      tumor specimens and, in 90% of the cells, chromosome 1p appeared to be involved
      in unbalanced translocations with different chromosomes, leading to variable
      losses of 1p. Previous cytogenetic data concerning chordoma are limited to 10
      sporadic tumors with an abnormal karyotype; although no tumor-specific
      rearrangements have been identified, chromosome 1p appears to be involved
      frequently.

PMID- 10077148
TI  - Cancer incidence and mortality in a cohort of chloroprene workers from Armenia.
AB  - We evaluated the risk of cancer among 1897 men and 417 women exposed to
      chloroprene (2-chloro-1,3-butadiene, CP) at a production plant in Yerevan,
      Armenia, between 1940 and 1988. The cohort was followed up for cancer incidence
      for the years 1979-1990 and for cancer mortality for 1979-1988. In the cohort,
      incidence and mortality from all cancers were below expectation, but increased
      incidence (standardized incidence ratio 3.27, 95% confidence interval [CI] 1.47
      7.27), and mortality (standardized mortality ratio 3.39, 95% CI 1.09-10.5) from
      liver cancer were noticed. A dose-response relationship was suggested between
      liver cancer and indices of CP exposure, such as duration of employment, duration
      of high CP exposure and cumulative exposure to CP. The risk of other neoplasms
      was not increased.

PMID- 10077149
TI  - Photodynamic therapy in women with cervical intraepithelial neoplasia using
      topically applied 5-aminolevulinic acid.
AB  - Photodynamic therapy (PDT) is a novel treatment modality that produces local
      tissue necrosis with laser light after prior administration of a photosensitizing
      agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in
      the photodynamic treatment of women with high-grade cervical intraepithelial
      neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from
      previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20%
      solution of 5-ALA was topically applied using a cervical cap. PDT was performed
      with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon
      ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed
      cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were
      performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100
      150 mW/cm2 was well tolerated. Local toxicity was minor as several patients
      reported burning sensations and vaginal discharge, but no necrosis, sloughing or
      scarring occurred. After 3 months, a significant reduction in the size of the
      ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT
      cycle. However, no significant improvement in CIN lesions was noted since cold
      knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after
      topical application of 5-ALA using an irradiation of 100 J/cm2 produces only
      minimal side effects. However, it does not appear to be effective in treating
      CIN.

PMID- 10077150
TI  - Influence of habitual smoking on gastric cancer by histologic subtype.
AB  - A comparative case-referent study was conducted using data from the Hospital
      based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), with the
      aim of clarifying whether histologic subtypes of gastric cancer exhibit different
      risk-factor patterns of habitual smoking. Our study comprised 995 histologically
      confirmed gastric-cancer cases [460 differentiated (intestinal type), 527 non
      differentiated (diffuse type) and 8 unclassified], identified via hospital cancer
      registry and surgical records, and 43,846 non-cancer outpatients at Aichi Cancer
      Center Hospital over the years 1988-1995. Odds ratios (ORs) were estimated by
      gender using logistic regression and adjusted for potential confounding factors.
      In males, a significantly increased OR of gastric cancer was observed for
      habitual smokers, and this was higher in the differentiated type than the non
      differentiated type and in younger than in older age groups. Risk patterns were
      less clear in females. Our results suggest that habitual smoking is associated
      more likely with the differentiated type of gastric cancer, particularly in
      younger cases.

PMID- 10077151
TI  - Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of
      smoking-related oral and pharyngeal cancers.
AB  - Several polymorphic glutathione S-transferase enzymes are involved in the
      detoxification of active metabolites of many potential carcinogens from tobacco
      smoke and may therefore be important in modulating susceptibility to smoking
      related cancers. As part of a hospital-based case-control study performed in
      France among Caucasian smokers, we studied GSTM1, GSTM3, GSTP1 and GSTT1 gene
      polymorphisms in 121 patients with oral cavity and pharyngeal cancers and 172
      hospital controls using peripheral blood DNA. An increase in risk was found among
      carriers of the GSTP1 (AG or GG) genotype (OR 1.6, 95% CI 1.0-2.8, p = 0.07) or
      the GSTT1 null genotype (OR 2.0, 95% CI 1.0-4.0, p = 0.05). The effect of these
      at-risk genotypes was most marked in subjects with a history of more than 30
      years of smoking, among whom the respective ORs were 2.0 (95% CI 1.0-3.9) and 3.3
      (95% CI 1.3-8.1), though the interaction tests between these genotypes and
      duration of smoking were not significant. In contrast, neither the GSTM1 null
      genotype nor the GSTM3 AA genotype was associated with oropharyngeal cancer risk
      (OR 0.9, 95% CI 0.5-1.5 and OR = 1.3, 95% CI 0.7-2.3, respectively). Our results
      thus suggest that GSTP1 and GSTT1 gene polymorphisms modulate susceptibility to
      smoking-related cancers of the oral cavity and pharynx.

PMID- 10077152
TI  - Reproductive risk factors for breast cancer by receptor status, histology,
      laterality and location.
AB  - It is well established that a woman's reproductive history influences her risk of
      breast cancer. We examined whether the effect of reproductive history was similar
      for different sub-types of breast cancer. The study was based on a population
      based cohort of 1.5 million Danish women born between 1935 and 1978, with
      individual information on births. Between 1978 and 1994, 10,790 incident cases of
      breast cancer were identified in a nationwide cancer registry, including detailed
      information on receptor status, histology, laterality and location of the tumour.
      Overall, the incidence of breast cancer was 13% lower in parous compared with
      nulliparous women. This reduction was significantly stronger for mucinous than
      for ductal carcinomas and for tumours located centrally than for those non
      central in the breast. Overall, the incidence in parous women increased by 10% by
      each 5-year postponement of their first birth. For the incidence of lobular
      carcinomas this increase was significantly stronger, and for mucinous carcinomas
      it tended to be stronger than for ductal carcinomas. For the incidence of
      centrally located tumours the increase was stronger than for non-centrally
      located tumours. On average, there was a 10% decrease in breast-cancer risk by
      each additional birth. This decrease was seen in most sub-types, but not for
      lobular carcinomas of for centrally located tumours. According to our findings,
      lobular and mucinous carcinomas and centrally located tumours may have risk
      factor profiles that differ from other types of breast cancer.

PMID- 10077153
TI  - Time trends in socio-economic differences in incidence rates of cancers of the
      breast and female genital organs (Finland, 1971-1995).
AB  - The magnitude of socio-economic differences in health varies between societies,
      and over time within societies. Even in the Nordic countries, where socio
      economic differences are not as striking as elsewhere, such differences have been
      observed. We have studied social class variation among 45- to 69-year-old Finns
      during 1971-1995 in the incidence of cancers of the breast, ovary, corpus and
      cervix uteri, vulva and vagina, by means of a computerised record linkage of the
      Finnish Cancer Registry and the 1970 Population Census, which included social
      class data. Cancers of cervix uteri (both invasive and in situ) and vagina were
      associated with low social class. Cancers of the breast (both in men and women)
      were most common in high social classes throughout the whole observation period
      1971-1995, whereas for cancer of the corpus uteri, the positive social class
      association disappeared in the early 1980s. For cancer of the vulva and ovary, no
      clear differences by social class were observed. We believe that socio-economic
      differences usually point to life styles or life conditions (e.g., reproductive
      patterns, viral infections, diet, physical activity, prevalence of overweight and
      obesity, smoking and alcohol consumption or combinations of these factors) that
      may be risk factors for the specific cancers studied.

PMID- 10077154
TI  - Recent declines in worldwide mortality from cutaneous melanoma in youth and
      middle age.
AB  - Trends in age-standardised death-certification rates for skin cancer [mainly
      cutaneous malignant melanoma (CMM)] over the period 1955-1995 were considered for
      22 developed countries (18 from Europe, Canada, the United States, Australia and
      New Zealand) on the basis of the World Health Organization database. Between 1955
      and 1984, mortality from CMM has been rising in both young adults (20 to 44
      years) and middle aged population (45 to 64 years) in most European countries,
      North America and Australia. Between 1985 and 1995, CMM mortality rates were
      still rising in several countries for middle-aged males, though, to a lesser
      extent, they were more favourable in middle-aged women and declined in young
      adults in most countries, particularly in northern Europe.

PMID- 10077155
TI  - Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer
      cells bearing c-ret proto-oncogene with reference to glial-cell-line-derived
      neurotrophic factor (GDNF).
AB  - Perineural invasion is a prominent clinical feature of pancreatic cancer which
      causes difficulty in curative resection. In the present study, the human
      pancreatic cancer cell lines, PaCa-2, AsPC-1, SW1990 and Capan-2, were all found
      to express abundant c-ret proto-oncogene mRNA and RET protein, a member of the
      receptor-tyrosine-kinase superfamily, identified as being a receptor for glial
      cell-line-derived neurotrophic factor (GDNF). In an invasion assay, the migration
      of pancreatic cancer cells was markedly induced by co-cultivation with human
      glioma cells, T98G or A172, capable of producing and secreting GDNF. Anti-GDNF
      antibody in conditioned media of glioma cells suppressed much of the migratory
      activity. Checkerboard analysis of the migration showed both chemotactic and
      chemokinetic activity of GDNF. There was no detectable expression of another GDNF
      receptor component, a glycosyl-phosphatidylinositol-linked receptor (GFR alpha
      1), in pancreatic-cancer cell lines, suggesting that the neural invasion of
      pancreatic-cancer cells spreads along a concentration gradient of GDNF produced
      from peripheral ganglions through direct interaction of GDNF with its receptor,
      the c-ret proto-oncogene product. Immunochemical localization of GDNF in human
      celiac ganglionic tissue supported this contention.

PMID- 10077156
TI  - Glucocorticoid hormone suppression of human neutrophil-mediated tumor cell
      cytostasis.
AB  - In the present study, we have investigated the effect of glucocorticoid hormones
      on neutrophil-mediated tumor cell cytostasis and found that hydrocortisone and a
      synthetic hormone, dexamethasone (Dex), inhibited cytostasis in the presence or
      absence of tumor necrosis factor-alpha. The effect of Dex was completely reversed
      by a glucocorticoid receptor antagonist, RU38486. To clarify the underlying
      mechanisms, we examined effects of Dex on the binding avidity of beta2 integrin
      on the neutrophil surface and how these might in turn affect neutrophil-to-tumor
      cell binding. Dex was found to inhibit these neutrophil properties, and RU38486
      completely suppressed both forms of Dex inhibition. Taken together, our findings
      suggest that glucocorticoid hormone inhibition of neutrophil-mediated tumor cell
      cytostasis is at least partially due to a lowering of the ligand binding avidity
      of beta2 integrin on the neutrophil surface.

PMID- 10077157
TI  - Characterization of intracellular pH gradients in human multidrug-resistant tumor
      cells by means of scanning microspectrofluorometry and dual-emission-ratio
      probes.
AB  - Multidrug-resistant cells are believed to contain a plasma-membrane-efflux pump
      which is hypothesized to expel anticancer drugs from the cytosol to the cell
      exterior. Many of these drugs are classified as weak bases whose binding to
      intracellular targets is pH-dependent. Slight alterations in intracellular pH
      gradients have been shown to affect accumulation, endocytosis and secretion of
      drugs. In this study, we developed a new method based on confocal spectral
      imaging analysis to determine intracellular pH gradients in sensitive and MDR
      tumor cells. Fluorescein isothiocyanate (FITC) and tetramethylrhodamine
      conjugated to dextran (FRD) and SNAFL-calcein-AM were used to determine pH in
      acidic compartments. Carboxy-SNARF1-AM was used to examine cytosolic pH. We
      observed that sensitive (HL60, K562, CEM and MCF7) cells exhibit lower acidity of
      the subcellular organelles than that corresponding to drug-resistant derivatives.
      Moreover, results obtained with carboxy-SNARF1-AM show that resistant cells
      display a more alkaline cytosolic pH. This results in a considerably larger pH
      gradient between the vesicular compartments and the cytosol of resistant cells
      than of sensitive cells. The lower pH gradient observed in sensitive cells may be
      related to a disruption in the organization of the trans-Golgi network (TGN). In
      drug-resistant cells, the organization of TGN appears compact. In addition,
      confocal microscopic analysis of cells labelled with FRD and SNAFL-calcein showed
      that sensitive cells contain a lower number of acidified vesicles. This suggest a
      diminished capacity of these cells to remove protonated drugs from the cytoplasm
      to secretory compartments followed by their secretion through the activity of the
      secretory and recycling pathways.

PMID- 10077158
TI  - The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer cells.
AB  - In human cancers, the co-operative role between cell-adhesion receptors and
      proteases capable of degrading matrix barriers remains poorly understood. We have
      previously reported that the epithelium-restricted integrin alpha(v)beta6 becomes
      highly expressed in colon cancer compared with normal mucosa and that
      heterologous expression of alpha(v)beta6 in colon cancer cells is associated with
      enhanced cell growth. Herein, we report that alpha(v)beta6 expression in colon
      cancer cells leads to a relative increase in secretion of the matrix
      metalloproteinase gelatinase B over its respective inhibitor and that this
      secretion parallels the level of cell-surface beta6 expression. The alpha(v)beta6
      mediated gelatinase B secretion is associated with increased proteolysis of
      denatured collagen at the cell surface, and inactivation of gelatinase B in beta6
      expressing tumour cells inhibits cell spreading and proliferation within 3
      dimensional collagen matrices. Our findings suggest that alpha(v)beta6-mediated
      gelatinase B secretion is important in the progression of human colon cancer.

PMID- 10077159
TI  - Expression profile of agonistic Smads in human breast cancer cells: absence of
      regulation by estrogens.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a cytokine expressed by mammary
      cells. While TGF-beta1 can inhibit the proliferation of human breast cancer
      cells, many cell lines are unresponsive to it. To shed light on the mechanisms
      underlying resistance to TGF-beta1, we examined expression of the mediators of
      TGF-beta1 signaling in the mammary carcinoma cell lines MCF-7, T47D, ZR-75-1, BT
      20, MDA-MB-231 and MDA-MB-468. The levels of mRNA encoding Smad2, 3 and 4 as well
      as the type II (TbetaRII) and type I (TbetaRI) membrane receptors were determined
      by Northern analysis and/or ribonuclease protection assays. Smad2 and Smad3 mRNAs
      were detected in all 6 cell lines examined, whereas Smad4 mRNA was not detected
      in MDA-MB-468 cells, which are known to harbor a homozygous deletion of the Smad4
      gene. TbetaRI was expressed in all 6 cell lines, whereas TbetaRII was not
      detected in ZR-75-1 and T47D cells. Of the cell lines tested, only MCF-7 cells
      were growth-inhibited by TGF-beta1. In contrast, only MDA-MB-231 cells showed
      induction of the PAI-1 promotor in response to TGF-beta1. We also examined the
      regulation of Smad mRNA expression by estrogens and androgens in ZR-75-1 cells.
      Neither estradiol nor dihydrotestosterone affected Smad2, 3 or 4 mRNA levels in
      ZR-75-1 cells. These results indicate that the lack of response to TGF-beta1 in
      the breast cancer cell lines examined can be attributed to the absence of either
      TbetaRII or the Smad4 gene product. Moreover, we show that the proliferative and
      transcriptional responses to TGF-beta1 are dissociable and that Smad expression
      is not regulated by sex steroids in ZR-75-1 cells.

PMID- 10077160
TI  - Examination of POU homeobox gene expression in human breast cancer cells.
AB  - Abnormal expression of homeobox genes may lead to the development of leukemias,
      lymphomas, and solid tumors. Expression of homeobox genes in mammary glands,
      however, has not been studied actively until recently. We have examined the
      expression of POU homeobox genes in human breast cancer cell lines and human
      breast tissue samples. Using a pair of degenerate primers for reverse
      transcription-polymerase chain reaction (RT-PCR) followed by DNA sequencing, we
      found that the human breast cancer cell line, MCF7, expresses at least 4 POU gene
      products: OCT1, OCT2, OCT3 and OCT11 (Skn-1a/i, Epoc-1). The expression of OCT1
      and OCT2 in other human breast epithelial cell lines was further determined by
      Western blot analyses and electrophoretic mobility shift assay. We were unable to
      detect OCT11 in human breast cancer cell lines using the anti rat Skn-1a/i
      antibody, although the expression of this gene in both human breast cancer cell
      lines and human primary breast tumors was detected by RT-PCR. OCT3 is an
      embryonic transcription factor. We found that this gene is also expressed in
      human breast cancer cell lines and all human primary breast carcinomas examined,
      but not in normal human breast tissue. Taken together, we have shown that several
      POU genes are expressed in human breast epithelial cells. As OCT3 expression was
      detected only in the breast cancerous cells, this embryonic transcription factor
      could play an important role in mammary gland carcinogenesis.

PMID- 10077161
TI  - Vascular endothelial growth factor expression in human neuroblastoma: up
      regulation by hypoxia.
AB  - Enhanced angiogenesis apparently contributes to the poor clinical outcome of
      human neuroblastoma, but the mechanisms have remained unclear. We report here
      that cultured human neuroblastoma cells express a bioactive endothelial cell
      growth factor indistinguishable from the angiogenesis stimulator vascular
      endothelial growth factor (VEGF). VEGF is present in neuroblastoma but not
      vascular endothelial cells, whereas the corresponding VEGF receptors (Flt-1 and
      Flk-1/KDR) are expressed in endothelial but not neuroblastoma cells. Exposure of
      neuroblastoma cells to hypoxia induces a marked increase in bioactive VEGF. VEGF
      is also present in human neuroblastoma specimens, with substantial amounts in
      apparently hypoxic neuroblastoma cells, eventually accumulating in tumor
      microvessels. Our results indicate that VEGF (i) is present in human
      neuroblastomas, (ii) is up-regulated by tumor hypoxia and (iii) may stimulate
      neuroblastoma angiogenesis by paracrine mechanisms, thereby contributing to the
      progression of human neuroblastomas. We suggest that inhibition of VEGF activity
      may represent a novel approach for the therapy of human neuroblastoma.

PMID- 10077162
TI  - Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by
      astrocytoma cells is mediated by Ras.
AB  - Vascular endothelial growth Factor (VEGF) has been identified as a key angiogenic
      factor involved in the growth and malignant progression of tumours. Glioblastoma
      multiforme (GBM) are the most common primary human brain tumours, histo
      pathologically characterized by intense tumour angiogenesis. GBMs do not harbour
      oncogenic Ras mutations, but there is a functional up-regulation of Ras signaling
      through activation of receptor tyrosine kinases overexpressed by these tumours.
      We demonstrate that Ras pathway activation regulates VEGF secretion in
      astrocytoma cell lines. Ras pathway inhibition was carried out using genetic and
      pharmacologic techniques. Astrocytoma cells that were transfected to express the
      dominant inhibitory mutant H-Ras(N17) demonstrated a reduction in VEGF secretion
      under both normoxic and hypoxic conditions. Cells treated with the farnesyl
      transferase inhibitor L-744,832 demonstrated similar reductions in VEGF
      secretion. Furthermore, astrocytoma cells expressing a constitutively
      phosphorylated and truncated EGF-R common in GBMs (EGFRvIII or p140(EGF-R))
      demonstrate further elevations in Ras activation, resulting in a further increase
      in VEGF secretion. We have previously demonstrated that activation of Ras plays a
      vital role in transducing mitogenic signals in human malignant astrocytoma cells.
      Our present results further extend the role of Ras activation in modulating
      tumour angiogenesis in these tumours. We propose that Ras may contribute to the
      angiogenic switch in astrocytomas.

PMID- 10077163
TI  - Induction of immunogenicity of a human renal-cell carcinoma cell line by TAP1
      gene transfer.
AB  - Reduced expression of the major-histocompatibility-complex(MHC)-class-I antigens
      has been demonstrated in renal-cell carcinoma (RCC), and appeared to be
      associated with deficiencies in the expression and function of different
      components of the MHC-class-I-antigen-processing pathway and poor recognition by
      cytotoxic T-lymphocytes (CTL). In order to investigate the role of peptide
      transporters for the immunogenic phenotype of RCC, tumor cells were stably
      transfected with the human TAP1A gene. While the TAP1 transfectants showed
      heterogeneous TAP1-transgene expression pattern of mRNA and protein, high TAP1
      expression and a TAP-controlled increase in MHC-class-I surface expression could
      be achieved in selected transfectants. IFN-gamma up-regulates the expression of
      MHC-class-I antigens and TAP1 both in control and in TAP1-transfected RCC cells
      to a similar level. No additive effect of TAP1 over-expression was observed in
      TAP1 transfectants. Although no enhanced CTL-mediated lysis was obtained,
      cytokine release was substantially increased in response to TAP1-transfected RCC
      cells, but not to control cells. Furthermore, TAP1 transfectants were able to
      stimulate the proliferation of allogeneic T cells. These studies suggest that
      abnormalities of MHC-class-I surface expression due to dysfunctional peptide
      transporters contribute to the immune escape phenotype of RCC cells and that the
      immune tolerance of RCC could be altered by TAP1-gene transfer.

PMID- 10077164
TI  - Retroviral expression of a mutant (Gly-533) human DNA topoisomerase I cDNA
      confers a dominant form of camptothecin resistance.
AB  - In previous studies, we isolated a mutant DNA topoisomerase I cDNA from a
      camptothecin (CPT)-resistant human T-lymphoblastic leukemia cell line, CPT-K5,
      and demonstrated that an amino acid change from Asp to Gly at residue 533 is
      responsible for the CPT resistance of the enzyme. In the present study, we have
      constructed a bicistronic retroviral vector, Ha-TM1-IRES-neo, that carries the
      mutant (Gly-533) TOP1 cDNA (TM1) and a neomycin-resistance gene to examine the
      effect of mutant DNA topoisomerase I (topo I) expression on CPT resistance of
      cells. HeLa S3 cells were transduced with Ha-TM1-IRES-neo, and the transduced
      cells were selected with G418. Two independently isolated populations of the G418
      resistant cells and 2 clones showed 1.7- to 1.8-fold higher resistance to CPT
      than the control cells. Integration and expression of the exogenous TOP1 were
      confirmed by genomic and RT-PCR analyses. The topo I enzyme (mixture of mutant
      and wild-type) expressed in the transduced cells showed 3-fold resistance to CPT
      in cleavable-complex-formation assay and DNA-relaxation assay. Mutant topo I
      activity in the transduced cells was as much as 10% that of the endogenous
      enzyme. Our results clearly show that expression of Gly-533 topo I confers a
      dominant form of CPT resistance in cells expressing wild-type topo I. The mutant
      TOP1 could be used for the protection of normal bone marrow cells of cancer
      patients from the severe hematotoxicity of CPT-derivative anti-tumor agents.

PMID- 10077165
TI  - Transformation is associated with an increase in sensitivity to TNF-mediated
      lysis as a result of an increase in TNF-induced protein tyrosine phosphatase
      activity.
AB  - Using the tumor necrosis factor (TNF)-resistant cell line B/CN and an anchorage
      independent variant, 10ME, we have shown a relationship between transformation
      and sensitivity to TNF. Here, we report a role for protein tyrosine
      phosphorylation in expression of these phenotypes. Several studies have
      demonstrated the involvement of protein phosphorylation in the TNF signaling
      pathways that leads to cell death. We show that TNF treatment of the TNF
      sensitive, transformed cells results in a marked increase in protein tyrosine
      phosphatase (PTP) activity and a decrease in protein tyrosine kinase (PTK)
      activity. In contrast, TNF treatment of the TNF-resistant, non-transformed
      parental cells results in a marked increase in PTK activity. Also, the PTP
      inhibitors vanadate and bromotetramisole decrease TNF lytic activity, indicating
      that the PTP activity observed is an integral part of the lytic process.
      Treatment of targets with vanadate prior to TNF exposure had no effect on TNF
      mediated lysis. In contrast, the addition of vanadate up to 4 hr after TNF
      treatment resulted in a decrease in TNF-mediated lysis. Our findings indicate
      that the phosphatase activity is induced after TNF binds its receptor. Our data
      also indicate that the decrease in TNF-mediated lysis caused by PTP inhibitors is
      not due to the inhibition of the TNF lytic mechanism. Instead, vanadate increases
      a TNF resistance mechanism; it does so by blocking the PTP-mediated inhibition of
      the TNF resistance mechanism. Further, the lineage relationship of these cell
      lines suggests that there is a biochemical relationship between anchorage
      independence, tumorigenicity and the protein tyrosine phosphorylation that
      governs sensitivity to TNF.

PMID- 10077166
TI  - Complete regression of human B-cell lymphoma xenografts in mice treated with
      recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 at doses tolerated by
      cynomolgus monkeys.
AB  - RFB4(dsFv)-PE38 is a recombinant immunotoxin in which the variable light domain
      (V(L)) is disulfide bonded via cysteine residues to the variable heavy domain
      (V(H)), which in turn is fused to PE38, a mutant form of Pseudomonas exotoxin A.
      RFB4 binds to CD22, which is a differentiation antigen expressed on the majority
      of B-cell leukemias and lymphomas. To examine the potential efficacy of
      RFB4(dsFv)-PE38 when administered at a dose schedule appropriate for phase I
      testing, mice bearing CA46 human CD22+ Burkitt's lymphoma xenografts were treated
      on alternate days i.v. for 3 doses (QOD x 3). Complete regressions were observed
      in 80% and 100% of mice treated with 200 and 275 microg/kg QOD x 3, respectively.
      The higher dose was 27% of the LD50 and 34% of the LD10 in mice. Because
      RFB4(dsFv)-PE38 is stable at 37 degrees C, it could also be given by continuous
      infusion using pumps placed in the peritoneal cavity; complete regressions also
      resulted from this mode of administration. To study toxicology, a pilot
      toxicology study of RFB4(dsFv)-PE38 was undertaken in cynomolgus monkeys, which
      like humans but unlike mice have CD22, which binds RFB4. Doses of 100 and 500
      microg/kg i.v. QOD x 3 were well tolerated, indicating that a dose that cured
      tumors in mice was tolerated by primates. Based on these preclinical results,
      RFB4(dsFv)-PE38 is being developed for the treatment of patients with CD22
      positive leukemias and lymphomas.

PMID- 10077167
TI  - Long-term survival and complete cures of B16 melanoma-carrying animals after
      therapy with tumor-targeted IL-2 and SEA.
AB  - The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent
      inducer of CTL activity and cytokine production in vivo. To engineer SAg for
      cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215
      tumor-reactive antibody. Strong reduction of lung metastasis was seen in mice
      carrying established lung metastases of the poorly immunogenic B16-C215 melanoma
      after Fab-SEA therapy. However, important anti-tumor effector functions, such as
      IFN-gamma secretion and CTL activity, gradually declined during therapy. In this
      study, we show that Fab-SEA immunotherapy is strongly potentiated by Fab-IL-2 co
      administration. Combined Fab-IL-2 and Fab-SEA therapy prolongs the immune
      response in vivo, limits the development of immunological unresponsiveness and
      promotes maximal anti-tumor effects. Significantly prolonged survival was noted
      in tumor-carrying animals treated with Fab-SEA/Fab-IL-2 as compared with Fab-SEA
      or Fab-IL-2 alone. Combination therapy resulted in complete cure in 90% of tumor
      bearing animals, whereas only 10% long-term survival was seen in Fab-SEA or Fab
      IL-2-treated animals. Single Fab-SEA therapy induced a hyporesponsive state after
      2 cycles of treatment. In contrast, the immune response after combination therapy
      was characterized by substantially augmented IFN-gamma and TNF-alpha production
      and strong CTL activity. Our data demonstrate that combined Fab-SEA and Fab-IL-2
      therapy prolongs the immune response in vivo and induced long-term survival of
      more than 90% of the animals carrying the highly aggressive B16 melanoma.

PMID- 10077168
TI  - Oxandrolone, used for treatment of wasting disease in HIV-1-infected patients,
      does not diminish the antiviral activity of deoxynucleoside analogues in
      lymphocyte and macrophage cell cultures.
AB  - Antiviral agents are the primary therapy for patients infected with HIV-1.
      However, supportive therapies are often necessary in addition to antiviral drugs
      because of the devastating wasting process associated with HIV-1 infection and
      AIDS. Oxandrolone, an anabolic steroid, is used in promoting weight gain and,
      most important lean body mass (LBM), in patients with HIV-1 disease. We
      investigated whether oxandrolone interferes with the antiviral activity of
      zidovudine (ZDV), dideoxyinosine (ddI), and dideoxycytidine (ddC) on HIV-1
      replication in peripheral blood lymphocytes and macrophage-monocytes. The
      nucleoside analogues had nanomolar 50% inhibitory concentrations (IC50) in
      peripheral lymphocytes. Combinations of nucleoside analogues and oxandrolone did
      not result in increased IC50 values. Oxandrolone used alone exhibited micromolar
      IC50 values in peripheral blood lymphocytes. Lack of interference was consistent
      for nucleoside concentrations up to 5 microM and for oxandrolone concentrations
      up to 100 microM in several combinations of drugs, viral strains, and peripheral
      lymphocytes and macrophages. We conclude that oxandrolone can be used for the
      promotion of weight gain in patients with AIDS-related wasting without
      interference with the antiviral effects of ZDV, ddI, or ddC.

PMID- 10077169
TI  - Clinical trials using HIV-1 RNA-based primary endpoints: statistical analysis and
      potential biases.
AB  - Clinical trial endpoints based on magnitude of reduction in HIV-1 RNA levels
      provide an important complement to endpoints based on percentage of patients
      achieving complete virologic suppression. However, interpretation of magnitude of
      reduction can be biased by measurement limitations of virologic assays,
      particularly lower and upper limits of quantification. Using data from two AIDS
      Clinical Trials Group (ACTG) studies, widely used crude methods of analyzing HIV
      1 RNA reductions were compared with methods that take into account censoring of
      HIV-1 RNA measurements. Such methods include Kaplan-Meier and censored regression
      analyses. It was found that standard crude methods of analysis consistently
      underestimated treatment effects. In some cases, the bias induced by crude
      methods masked statistically significant differences between treatment arms.
      Although statistically significant, adjustment for baseline HIV-1 RNA levels had
      little effect on estimated treatment differences. Furthermore, convenient
      parametric analyses performed as well as more complex nonparametric analyses. It
      is concluded that conveniently implemented censored data analyses should be
      conducted in preference to widely used crude analyses of magnitude of HIV-1 RNA
      reduction. To obtain complete information about virologic response to
      antiretroviral therapy, such analyses of magnitude of virologic response should
      be used to complement analyses of the percentage of patients having complete
      virologic suppression.

PMID- 10077170
TI  - Studies of body composition and fat distribution in HIV-infected and control
      subjects.
AB  - OBJECTIVE: Recent studies have documented alterations in body fat distribution
      that have been associated with protease inhibitor therapy. We compared body
      composition, including measurements of fat distribution, in 96 HIV-infected
      subjects studied since January 1996 (current HIV), subjects seen prior to January
      1996 (previous HIV), and healthy controls. DESIGN: Retrospective cross-sectional
      studies of subjects matched by gender, race, age, and height. METHODS: Body
      weight, height, body cell mass by whole-body counting of 40K plus fat, fat-free
      mass, and body fat distribution by anthropometry were measured. RESULTS: Current
      HIV men weighed more (p = .025) and had more body cell mass than previous HIV
      men, but less than controls (p < .001). In women, the between group differences
      in fat were greater than the differences in body cell mass. Current and previous
      HIV study subjects had lower indices of subcutaneous and higher indices of
      visceral fat than controls. In current HIV subjects, body fat distribution was
      significantly associated with log plasma HIV RNA content but not with
      antiretroviral or protease inhibitor usage, nor with CD4+ lymphocyte counts. In 7
      of 9 current HIV subjects studied, 24-hour urinary free cortisol excretion was
      abnormally high. CONCLUSIONS: Alterations in body fat distribution are a
      characteristic feature in HIV infection. The occurrence of increased visceral fat
      content and decreased subcutaneous fat content preceded the era of combination
      antiretroviral therapy. The alteration in fat distribution may be affected by
      plasma HIV RNA content rather than antiretroviral or protease-inhibitor therapy.
      The body composition alterations might be associated with endogenous
      hypercortisolism.

PMID- 10077171
TI  - Stability of cutaneous anergy in women with or at risk for HIV infection. HIV
      Epidemiology Research Study Group.
AB  - OBJECTIVE: To study the stability of cutaneous anergy in women with or at risk
      for HIV infection. DESIGN: Prospective multicenter cohort study METHODS:
      Interviews, CD4+ lymphocyte counts, and intradermal skin testing with mumps,
      Candida, and tetanus toxoid antigens were performed on two occasions at a median
      interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women;
      only 10 (2%) HIV-seropositive women were taking highly active antiretroviral
      therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was
      defined as induration <2 mm to all three antigens. RESULTS: Skin test reactivity
      at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were
      not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were
      anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07
      2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who
      were previously anergic, compared with 77 of 267 (29%) who were not previously
      anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women,
      CD4+ lymphocyte counts were lower at both initial and follow-up testing in those
      who remained anergic than in those who reacted at follow-up (p < .001). The
      relative risks for anergy at retesting of initially anergic seropositive women,
      compared with initially reactive seropositive women, were related to CD4+ level;
      2.5 (95% CI, 1.4-4.3) for CD4+ counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for
      CD4+ counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+ counts >500
      cells/mm3. CONCLUSIONS: Although anergic HIV-seropositive women may become
      reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as
      well as lower CD4+ counts. Stability of anergy is greatest in HIV-seropositive
      women with low CD4+ counts.

PMID- 10077172
TI  - Phase II, randomized, open-label, community-based trial to compare the safety and
      activity of combination therapy with recombinant interferon-alpha2b and
      zidovudine versus zidovudine alone in patients with asymptomatic to mildly
      symptomatic HIV infection. HIV Protocol C91-253 Study Team.
AB  - OBJECTIVES: To compare, in a community-based therapeutic setting, the safety,
      tolerance, and efficacy of combination therapy with recombinant interferon
      alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy. DESIGN: Open
      label, two-armed, randomized study. PATIENTS AND METHODS: Asymptomatic or
      minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4
      count of 200 to 500 cells/microl, and < or = 6 months of prior ZDV therapy
      received ZDV 100 mg orally five times daily. Patients randomized to rIFN-alpha2b
      received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million
      IU three times weekly thereafter. The groups were compared with respect to
      adverse events (AEs), dosing modifications, treatment discontinuation, clinical
      endpoints and changes in CD4 count. A virology substudy compared the treatments
      with respect to HIV viral load and development of ZDV resistance. RESULTS:
      Between October, 1991 and January, 1993, 139 patients were randomized to
      combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue,
      myalgias, and sweating occurred significantly more often with combination therapy
      (p < .001). Study subjects receiving combination therapy showed modest but
      significantly greater weight loss (p = .0001), a significantly higher frequency
      of any abnormal laboratory test result (p = .002), neutropenia (p = .002), and
      leukopenia (p = .02), and also required dosage reduction for hematologic toxicity
      significantly more often (p < .05) than those in the ZDV monotherapy arm. No
      statistically significant differences were found between the groups with respect
      to development of specific AIDS-defining events, overall event rate, time to
      events, or change in performance status or CD4+ counts, or percentages or
      development of ZDV resistance. Viral burden, reflected by serum p24 antigen and
      quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater
      at baseline in the combination therapy group. Baseline SI phenotype predicted
      progression to AIDS (p = .004, chi2), whereas intermediate susceptibility to ZDV
      predicted development of ZDV resistance (p < .005, chi2). The annual rate of
      development of phenotypic resistance to ZDV was 16.8% and was not affected by
      administration of rIFN-alpha2b. CONCLUSIONS: At the doses and schedule used in
      this study, the combination of ZDV with rIFN-alpha2b was not therapeutically
      superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b
      to ZDV did not prevent or delay the development of ZDV resistance.

PMID- 10077173
TI  - Lack of association between hepatitis C infection and development of AIDS-related
      lymphoma.
AB  - Hepatitis C virus (HCV) has been associated with various lymphoproliferative
      disorders, and a high prevalence (9%-32%) of chronic HCV infection has been
      demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has
      been demonstrated in approximately 40% of certain populations of HIV-infected
      individuals. Because of this high prevalence of coinfection by HIV and HCV, the
      known relations between HCV and lymphoproliferative disorders, and the
      association of HIV and B cell lymphoma, the potential association between chronic
      HCV and the development of AIDS-related lymphoma was examined. The prevalence of
      HCV infection in HIV-infected patients with lymphoma was compared with that in
      patients with AIDS, diagnosed on the basis of an illness other than lymphoma.
      Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV
      infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum.
      The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and
      43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1 %) men with
      lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with
      AIDS-related lymphoma, no relation was found between HCV infection and lymphoma
      histology or site. History of use of injected illicit drugs was associated with a
      significantly elevated risk of HCV infection in the combined group of lymphoma
      and other AIDS patients. The current study demonstrates no relation between dual
      infection by HIV and HCV and subsequent increased risk of lymphoma.

PMID- 10077174
TI  - HIV infection of the central nervous system is characterized by rapid turnover of
      viral RNA in cerebrospinal fluid.
AB  - To assess the kinetics of viral replication and decay in cerebrospinal fluid
      (CSF), we studied the short-term effects of highly active antiretroviral therapy
      (HAART) on CSF HIV-1 RNA concentrations. In 15 HIV-positive patients, HIV RNA
      concentrations were measured in paired CSF and plasma/serum samples. Samples were
      obtained prior to and 5 to 24 days after initiation or change of HAART. The short
      term effects of interruption of HAART were tested in 2 patients. Viral load was
      measured by the Roche Amplicor assay. During HAART, in 12 of 15 patients a
      significant reduction of CSF HIV RNA concentration was observed, ranging from
      0.55 to 2.77 log10 (median, 1.37 log10). This was paralleled by a reduction of
      blood viremia ranging from 0.12 to 3.0 log10 (median, 1.65 log10). The median
      half-life, as calculated from the slopes of the two time-point measurements, for
      CSF and blood viral load was 2.66 and 2.36 days, respectively. In 2 patients, CSF
      viral load remained essentially unchanged despite substantial reduction of plasma
      viral load. In 1 patient, after interruption of HAART, a rapid increase of HIV
      RNA in the CSF and blood was seen. No correlation was found between the CSF:blood
      albumin ratio as a measure of the functional integrity of the blood-CSF barrier
      and the ratio of CSF:blood RNA concentration, which suggests that no major
      passive influx of HIV RNA moves from the blood into the CSF compartment. However,
      a correlation existed between the CSF cell count and the CSF viral load (r =
      0.74; p < .003). We conclude that, in most HIV-infected individuals, the decay of
      viral load in the CSF is similarly rapid as that seen in plasma. The rapid
      kinetics of virus found in the CSF suggest that it may be produced by rapidly
      proliferating cells, such as lymphocytes.

PMID- 10077175
TI  - Impact of tuberculosis on the body composition of HIV-infected men in Brazil.
AB  - OBJECTIVE: Tuberculosis (TB) is the commonest HIV-related opportunistic infection
      in many developing countries and is thought to be a frequent underlying cause of
      HIV-associated wasting. We have used reference water dilution methods to examine
      the body composition changes associated with TB and to assess the severity and
      pattern of wasting. METHODS: The study was conducted at a charitable support
      house for poor and homeless HIV-infected people in Rio de Janeiro, Brazil. Male
      patients who were HIV-positive and receiving treatment for active TB (HIVTB+) and
      HIV-infected controls without TB (HIVTB-) were studied. Total body water (TBW)
      and extracellular water (ECW) were measured by giving oral doses of deuterium
      oxide and sodium bromide, respectively, and determining enrichment in plasma
      after 4 hours. Intracellular water (ICW), body cell mass (BCM), lean body mass
      (LBM) and fat mass were calculated from these parameters using standard
      equations. RESULTS: HIVTB+ (n = 11) and HIVTB- (n = 12) groups were similar in
      age, height, CD4 count and HIV risk factors. HIVTB+ men had significantly lower
      mean ICW (13.2 versus 16.6 kg; p = .02) and BCM (18.4 versus 23.0 kg; p = .02), a
      relative expansion of ECW (35.0 versus 30.0 L/kg body weight; p = .04), and small
      and nonsignificant reductions in total body weight (58.0 versus 62.1 kg; p =
      .26), LBM (45.5 versus 47.7 kg; p = .33) and fat mass (12.5 versus 14.4 kg; p =
      .51) compared with HIVTB- controls. BCM in the HIVTB+ group was similar to
      reference values for severe malnutrition. The relative depletion of BCM appeared
      excessive in comparison with reference values for uncomplicated starvation.
      CONCLUSION: The nutritional status of HIVTB+ patients was significantly worse
      than HIVTB- patients. Body weight and LBM underestimated the nutritional deficit,
      and measurement of BCM is therefore necessary to appreciate the extent of
      malnutrition in such patients. Malnutrition in HIVTB+ patients is severe and may
      therefore contribute to decreased survival. Hypermetabolism appears to play a
      role in the wasting process in patients coinfected with HIV and TB.

PMID- 10077176
TI  - Psychoactive drug use and progression of HIV infection.
AB  - Early in the history of the AIDS epidemic there was clear evidence of differences
      in the outcomes of HIV infection between injecting drug users and men who have
      sex with men. There were also some indications that high levels of nonsterile
      drug injection may increase the progression of HIV infection. Recent
      epidemiologic studies indicate no differences in rates of progression to AIDS
      among drug injectors, men who have sex with men, or persons infected through
      heterosexual contact. In vitro and animal studies suggest that the effects of
      different psychoactive drugs on HIV infection may be negative, positive, or
      mixed, and that the effects of a psychoactive drug on immune functioning may
      differ among acute administration, chronic administration, or cessation of
      chronic administration. Although the current epidemiologic data do not provide
      support for the hypothesis that psychoactive drug use will have any important
      effects on the course of HIV infection, possible interactions between
      psychoactive drugs and antiviral medications and medication adherence issues
      among drug users are important areas for AIDS research. Relations between
      psychoactive drug use, the nervous system, and the immune system are a promising
      area for basic research.

PMID- 10077177
TI  - Direct comparison of time to AIDS and infectious disease death between HIV
      seroconverter injection drug users in Italy and the United States: results from
      the ALIVE and ISS studies. AIDS Link to Intravenous Experiences. Italian
      Seroconversion Study.
AB  - OBJECTIVE: To compare the rate of HIV disease progression in a sample of polydrug
      injectors (AIDS Link to Intravenous Experiences [ALIVE] study) with that in a
      sample of predominantly opiate injectors (Italian Seroconversion Study [ISS]).
      DESIGN: Prospective cohort studies of HIV-positive individuals whose date of
      seroconversion (SC) is known with a good degree of precision. The ALIVE study
      involves a community-based cohort of injection drug users (IDU) in the United
      States and the ISS reports on a clinic-based cohort of seroconverters in Italy
      with different exposure modalities to HIV. METHODS: Data from the two cohorts
      were combined. The date of SC was estimated as the midpoint in time between the
      last negative and the first positive HIV test. Time-to-event (i.e., AIDS or death
      from an infectious disease) statistical methods were used. Relative hazards (RH)
      of progression to event were adjusted by age at SC, gender, and year of SC.
      RESULTS: Of the 1003 IDUs (251 from ALIVE and 752 from ISS), 226 progressed to
      AIDS, and 146 died after AIDS or from an infectious disease; of these, 10 were
      without an AIDS diagnosis. The two groups of IDUs differed in terms of age at SC
      (median, 35 years for ALIVE and 25 years for ISS), proportion of women (24%
      versus 31%), race (7.6% versus 100% white), and year of seroconversion (i.e., ISS
      participants seroconverted, on average, earlier than ALIVE participants).
      Although the univariate analysis suggested possible differences for progression
      to AIDS, or to death from infectious disease between cohorts, multivariate
      analyses that adjusted for age showed no significant differences by cohort,
      gender, race, or time of seroconversion. The median time to AIDS for 25-year-old
      persons was 12.3 years for ALIVE and 11.8 years for ISS; for 35-year-old persons,
      it was 8.5 and 8.2 years, respectively. These estimates were similar to those for
      non-IDUs observed in the ISS and to those from large cohort of homosexual men.
      CONCLUSION: Our results confirm the importance of accounting for age when
      considering the incubation period for HIV infection. Despite differences in drug
      use characteristics, the similar median times to AIDS, for each age, between the
      two cohorts of IDUs and between the IDUs and the non-IDUs suggest a negligible
      effect of injection drug use on HIV progression.

PMID- 10077178
TI  - Trends in injection risk behaviors in a sample of New York City injection drug
      users: 1992-1995.
AB  - OBJECTIVES: This study assessed the relation between year of recruitment into an
      AIDS prevention project and likelihood of engaging (yes/no) in injection risk
      behaviors. METHODS: In total, 834 injection drug users were recruited over a 44
      month period (January 1992-August 1995) in New York City. Logistic regression was
      used to examine trends in three behaviors, across four successive annual cohorts:
      using needles/syringes that were previously used by another person, using
      injection supplies (e.g., cookers, cotton, rinse water) that had been previously
      used, and giving or lending of used needles/syringes to another person. RESULTS:
      Significant (p < .0001) decreasing trends occurred in two behaviors: giving or
      lending of used needles/syringes to another person and use of injection supplies
      that had been used by another person. Sample characteristics were generally
      consistent over time and did not obviate significant injection risk trends.
      CONCLUSIONS: Decreasing trends in injection risk behaviors could not be explained
      by changing sample characteristics. Even though some injectors report engaging in
      risky injection practices, the confluence of numerous AIDS prevention efforts in
      the 1990s has contributed to an overall reduction in the likelihood of such
      behaviors.

PMID- 10077179
TI  - Incidence of discontinuation of highly active antiretroviral combination therapy
      (HAART) and its determinants.
AB  - OBJECTIVE: To determine the incidence and determinants for discontinuation of
      initial highly active antiretroviral therapy (HAART). DESIGN: In this
      retrospective follow-up study from hospital files and pharmacy dispensing data, a
      standard dataset was collected including patient characteristics, therapy
      characteristics, and HIV-monitoring parameters (e.g., CD4+ lymphocyte counts,
      viral load determinations). Kaplan-Meier estimates of the cumulative probability
      of discontinuation of initial HAART were calculated. Cox proportional hazard
      analysis was used to identify determinants for discontinuation of initial HAART.
      PATIENTS: All patients starting HAART (n = 99) during June 1996 to February 1997
      at our regional AIDS center. MAIN OUTCOME MEASURES: Incidence and determinants
      for discontinuation of HAART. RESULTS: During the mean follow-up of 450+/-10
      days, 27 patients switched initial HAART, 3 patients stopped any antiretroviral
      therapy. Reasons for switching were increasing viral load (18x), insufficient
      decrease of viral load (3x), and adverse events (6x). Nonnaivete for
      antiretroviral therapy and a lower CD4+ lymphocyte count at start were identified
      as determinants for discontinuation of initial HAART. CONCLUSIONS: The overall
      incidence density for discontinuation of initial HAART was 25 per 100
      patients/year. The main reason for switching was an increasing viral load. CD4+
      lymphocyte counts at start and nonnaivete for antiretroviral therapy were
      identified as determinants for discontinuation.

PMID- 10077180
TI  - Incidence and risk factors for heterosexually acquired HIV in an inner-city
      cohort of women: temporal association with pregnancy.
AB  - BACKGROUND: A growing proportion of AIDS cases in the United States are due to
      heterosexual transmission of HIV, particularly in women. The risk of
      heterosexually acquired HIV was prospectively studied in a cohort of inner-city
      women with no history of parenteral drug use. METHODS: Study participants were
      evaluated at 6-month intervals for the presence of HIV antibody, sexually
      transmitted diseases, self-reported sexual behavior, and drug use by self-report
      and urine screening. RESULTS: Of 449 initially HIV-negative women who were seen
      at least once in follow-up, 4 seroconverted to HIV, with a cumulative incidence
      of 2.4% at 30 months. Risk factors for HIV seroconversion included nonparenteral
      drug use (p < .02) and anal intercourse (p < .01). Sexually transmitted diseases
      were not associated with HIV, although the power to detect such an association
      was limited. In addition, 3 of 4 seroconverters became pregnant, yielding a rate
      of 55.5 pregnancies/100 person-years of follow-up compared with a rate of 11.1
      pregnancies/100 person-years of follow-up in nonseroconverters (p < .03).
      CONCLUSION: The incident rate of heterosexually acquired HIV in this inner-city
      U.S. cohort of women who were not using parenteral drugs is comparable with that
      reported in some developing countries where heterosexually acquired HIV is
      endemic. Most seroconversions appeared related to risk behavior seen in
      association with nonparenteral drug use. The previously unreported association of
      incident HIV infection with pregnancy in this cohort may be related to either
      behavioral or biologic factors.

PMID- 10077181
TI  - Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected
      pregnant and nonpregnant women. Women and Infants Transmission Study.
AB  - OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on
      cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their
      pregnancy status, and historical and clinical factors. METHODS: Study enrollment
      Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic
      evaluation. The rates of SIL were compared with pregnancy status,
      immunosuppression, presence of sexually transmitted diseases (STDs) and
      demographic features. RESULTS: Rates of low grade SIL were similar for pregnant
      and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of
      them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had
      invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95%
      confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3)
      were associated with SIL. An association between herpes simplex and SIL (OR =
      3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low
      prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a
      cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence
      of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although
      pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated
      with immunosuppression, cervical inflammation, and herpes simplex. Closer
      surveillance of HIV-1-infected women with these risk factors may be warranted.

PMID- 10077182
TI  - Evaluation of behavioral and social issues among Thai HIV vaccine trial
      volunteers.
AB  - Behavioral and social issues were investigated in phase I/II preventive HIV
      vaccine trial volunteers in Thailand. These included risk behavior, HIV
      knowledge, distress, and social experiences associated with trial participation.
      Data were collected at baseline and at 4- and 8-month follow-up visits.
      Volunteers reported relatively low levels of risk behaviors at baseline and at
      the follow-up visits. About one fifth reported overtly negative reactions from
      family or friends. No problems with discrimination in employment, health care, or
      insurance were reported. Findings add to the evidence suggesting the feasibility
      of phase I/II prophylactic HIV vaccine trials with low-risk volunteers in
      Thailand.

PMID- 10077183
TI  - Few clues for AIDS vaccines from structural data on gp120 and its receptors and
      antibodies.

PMID- 10077184
TI  - Recent dramatic decrease in AIDS cases and HIV-related deaths contrasts with
      stable rate of new HIV-positive patients detected in Lyon, France, from 1988 to
      1997.

PMID- 10077185
TI  - Characterization of the Hansenula polymorpha CPY gene encoding carboxypeptidase
      Y.
AB  - We have isolated the Hansenula polymorpha CPY gene encoding carboxypeptidase Y
      (Hp-CPY). The deduced amino acid sequence revealed that Hp-CPY consists of 541
      amino acids and has a calculated Mr of 60,793. The protein is highly similar to
      Saccharomyces cerevisiae CPY (61.8% identity). At the N-terminus of Hp-CPY
      signals for the entry into the secretory pathway and subsequent sorting to the
      vacuole were identified. Immunocytochemically, using monospecific antibodies
      raised against Hp-CPY, the protein was localized to the vacuole. On Western
      blots, a diffuse protein band was observed in extracts of H. polymorpha cells,
      suggesting that the protein is glycosylated. This was confirmed by
      endoglycosidase H treatment, which resulted in a strong reduction of the apparent
      Mr of the protein. We have investigated the effect of CPY deletion on the
      degradation of peroxisomes, an autophagous process that occurs when the
      organelles become redundant for growth. In deltacpy cells peroxisomal proteins
      were degraded in the vacuole as efficiently as in wild-type H. polymorpha cells,
      indicating that CPY is not a major proteinase in this pathway.

PMID- 10077186
TI  - Dynamic responses of reserve carbohydrate metabolism under carbon and nitrogen
      limitations in Saccharomyces cerevisiae.
AB  - The dynamic responses of reserve carbohydrates with respect to shortage of either
      carbon or nitrogen source was studied to obtain a sound basis for further
      investigations devoted to the characterization of mechanisms by which the yeast
      Saccharomyces cerevisiae can cope with nutrient limitation during growth. This
      study was carried out in well-controlled bioreactors which allow accurate
      monitoring of growth and frequent sampling without disturbing the culture. Under
      glucose limitation, genes involved in glycogen and trehalose biosynthesis (GLG1,
      GSY1, GSY2, GAC1, GLC3, TPS1), in their degradation (GPH1, NTHI), and the typical
      stress-responsive CTT1 gene were coordinately induced in parallel with glycogen,
      when the growth has left the pure exponential phase and while glucose was still
      plentiful in the medium. Trehalose accumulation was delayed until the diauxic
      shift, although TPS1 was induced much earlier, due to hydrolysis of trehalose by
      high trehalase activity. In contrast, under nitrogen limitation, both glycogen
      and trehalose began to accumulate at the precise time when the nitrogen source
      was exhausted from the medium, coincidentally with the transcriptional activation
      of genes involved in their metabolism. While this response to nitrogen starvation
      was likely mediated by the stress-responsive elements (STREs) in the promoter of
      these genes, we found that these elements were not responsible for the co
      induction of genes involved in reserve carbohydrate metabolism during glucose
      limitation, since GLG1, which does not contain any STRE, was coordinately induced
      with GSY2 and TPS1.

PMID- 10077187
TI  - Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide
      excision repair in the yeast Saccharomyces cerevisiae.
AB  - The OGG1 gene of Saccharomyces cerevisiae encodes a DNA glycosylase that excises
      7,8-dihydro-8-oxoguanine (8-OxoG). When compared to wild-type, ogg1 mutants show
      an increase in the frequency of GC to TA transversions, indicating a role for
      Ogg1 in the repair of 8-OxoG. Here we report an increased frequency of forward
      mutation to canavanine resistance in mutants defective in the nucleotide excision
      repair (NER) gene RAD14. This was not increased further in strains additionally
      defective in OGG1. However, when compared to strains solely defective in OGG1,
      ogg1radl4 mutants displayed an increase in spontaneous GC to TA transversions.
      Intriguingly, reversion of the lys1-1 ochre allele was not increased in rad14
      mutants, suggesting that oxidative base damage may only represent a substrate for
      NER in certain regions of the genome. We also examined repair of oxidative DNA
      damage by transforming mutant strains with plasmid DNA treated with methylene
      blue plus visible light. Mutants defective in OGG1 showed no significant
      reduction in transformation efficiency compared with wild-type strains. In
      contrast, disruption of RAD14 reduced the efficiency of transformation, yet there
      was no further decrease in an ogg1rad14 mutant. This strongly supports a role for
      NER in the repair of oxidative base damage in yeast, and differs from similar
      experiments carried out in E. coli, where transformation efficiency is only
      reduced in mutants defective in both fpg and uvrA. Finally, the repair of Fpg
      sensitive sites was examined at the MATalpha and HMLalpha mating type loci, and
      NER was found to play a role in their removal.

PMID- 10077188
TI  - Systematic identification, classification, and characterization of the open
      reading frames which encode novel helicase-related proteins in Saccharomyces
      cerevisiae by gene disruption and Northern analysis.
AB  - Helicase-related proteins play important roles in various cellular processes
      incuding DNA replication, DNA repair, RNA processing and so on. It has been well
      known that the amino acid sequences of these proteins contain several conserved
      motifs, and that the open reading frames (ORFs) which encode helicase-related
      proteins make up several gene families. In this study, we have identified 134
      ORFs that encode helicase-like proteins in the Saccharomyces genome, based on
      similarity with the ORFs of authentic helicase and helicase-related proteins.
      Multiple alignment of the ORF sequences resulted in the 134 ORFs being classified
      to 11 clusters. Seven out of 21 previously uncharacterized ORFs (YDL031w,
      YDL070w, YDL084w, YGL150c, YKL078w, YLR276c, and YMR128w) were identified by
      systematic gene disruption, to be essential for vegetative growth. Three
      (YDR332w, YGL064c, and YOL095c) out of the remaining 14 dispensable ORFs
      exhibited the slow-growth phenotype at 30 degrees C and 37 degrees C.
      Furthermore, the expression profiles of transcripts from 43 ORFs were examined
      under seven different growth conditions by Northern analysis and reverse
      transcription-polymerase chain reaction, indicating that all of the 43 tested
      ORFs were transcribed. Interestingly, we found that the level of transcript from
      34 helicase-like genes was markedly increased by heat shock. This suggests that
      helicase-like genes may be involved in the biosynthesis of nucleic acids and
      proteins, and that the genes can be transcriptionally activated by heat shock to
      compensate for the repressed synthesis of mRNA and protein.

PMID- 10077189
TI  - Analysis of TFIIH subunit through isolation of the gene from Schizosaccharomyces
      pombe corresponding to that of Saccharomyces cerevisiae SSL1, reveals the
      presence of conserved structural motifs.
AB  - We isolated a Schizosaccharomyces pombe (Sz. pombe) gene encoding the counterpart
      of the TFIIH subunit Homo sapiens (H. sapiens) p44 and Saccharomyces cerevisiae
      (S. cerevisiae) SSL1, and we named this gene product p47. Contrary to the case of
      SSL1, which is an essential gene of S. cerevisiae, p47 is not essential for the
      viability of Sz. pombe. The deduced amino acid sequence revealed that this TFIIH
      subunit is highly conserved during evolution. Comparison of the primary
      structures revealed differences in the predicted positions of introns in the
      Caenorhabditis elegans (C. elegans) gene encoding the p47 counterpart found
      during the genome project. A charged cluster in the N-terminal region is present
      in the two yeasts. Two putative zinc-binding motifs, an extended C2H2 zinc finger
      with a 'C8 motif' and a second putative zinc-binding motif common to the two
      TFIIH subunits, were also found, the former being completely conserved. The
      latter motif consists of five cysteine residues and is also present in hp44, SSL1
      and another TFIIH subunit, human p34 (hp34). Since one zinc atom can bind to four
      ligands in zinc-binding motifs, the conservation of cysteine residues was given
      attention. This motif is completely conserved in p47 homologues derived from the
      four species. As one cysteine residue is not conserved among the homologues of
      hp34, the consensus of this motif is concluded to be Cys X2-Cys-X(10,12)-Cys-X2
      Cys. This nucleotide sequence has been deposited in the GenBank Data Library
      under Accession Number AF017646.

PMID- 10077190
TI  - Current awareness on yeast.

PMID- 10077191
TI  - So where is the proof?

PMID- 10077192
TI  - Antibiotic prophylaxis in orthognathic surgery: a 1-day versus 5-day regimen.
AB  - PURPOSE: The effect on infection rates of 1-day and 5-day administration of
      prophylactic antibiotics in orthognathic surgical procedures was compared.
      PATIENTS AND METHODS: A prospective, randomized, double-blind clinical trial
      using placebo was conducted. Thirty patients were distributed equally between two
      groups. Each group received penicillin G, two million units intravenously,
      immediately preoperatively, and one million units intravenously every 3 hours
      intraoperatively and once postoperatively 3 hours after the last intraoperative
      dose. Group 1 then received penicillin G, one million units intravenously, every
      6 hours for eight doses, followed by penicillin V suspension 300 mg orally every
      6 hours for eight doses. Group 2 received placebo in a similar dosing schedule.
      The wounds were inspected on a regular schedule and evaluated for infection
      according to criteria established by the Centers for Disease Control. RESULTS:
      One of 15 patients in group 1 (6.7%) and 9 of 15 patients (60%) in group 2 became
      infected. The overall infection rate was 33.3%. There was a statistically
      significant difference in rates of infection between the two groups (P < .01).
      CONCLUSION: Antibiotic prophylaxis for orthognathic surgical procedures should
      continue beyond the immediate postoperative period. Five days of antibiotic
      administration appears to provide adequate coverage.

PMID- 10077193
TI  - Microvascular reconstruction of the skull base: indications and procedures.
AB  - PURPOSE: The aim of the current study was to review the use of free tissue
      transfer for reconstruction of the skull base and for coverage of intracranial
      contents. PATIENTS AND METHODS: From 1990 until 1996, revascularized flaps were
      transferred to the skull and the skull base in 11 patients in whom
      intracranial/extracranial resection of tumors of the skull base was performed in
      cooperation with the Department of Neurosurgery. The defects resulted from
      removal of squamous cell carcinomas (n = 4), basal cell carcinomas (n = 4),
      malignant melanoma, malignant schwannoma, and malignant meningioma. Defect repair
      was accomplished by revascularized transfer of latissimus dorsi muscle flaps in
      seven cases and rectus abdominis flaps and forearm flaps in two cases each. In
      five patients with extensive intracranial tumor spread, reconstruction was
      performed for palliative reasons. RESULTS: A safe soft tissue closure of the
      intracranial and intradural space was achieved in all patients, whereas the
      contour of the facial skull and the neurocranium was satisfactorily restored at
      the same time. By using the entire length of the grafted muscle, the vascular
      pedicle could be positioned next to the external carotid artery and conveniently
      connected to the cervical vessels. The mean survival time of the patients with
      palliative treatment was 8.4 months, with an average duration of hospital stay of
      24.5 days. CONCLUSIONS: Despite the increased surgical effort of revascularized
      tissue transfer, microvascular reconstruction of large skull base defects appears
      to be justified, even as a palliative measure.

PMID- 10077194
TI  - Results of intentional replantation of molars.
AB  - PURPOSE: This study evaluated the treatment outcome of intentional replantation
      of molars. PATIENTS AND METHODS: Twenty-nine patients were treated with
      intentional replantation because conventional apicoectomy was not possible. The
      success rate was judged by clinical and radiographic parameters. RESULTS: One
      molar (3%) had to be removed because of pain and mobility 4 weeks postsurgery,
      and three molars (11%) had to be removed during the first year because of
      periodontal problems. Four molars (14%) showed periodontal problems or root
      resorption, but are still in function and causing no obvious problems to the
      patients. Twenty-one molars (72%) were successfully treated. CONCLUSION:
      Intentional replantation is a reliable and predictable treatment for those cases
      in which conventional apicoectomy is hampered because of anatomic limitations or
      patient factors.

PMID- 10077195
TI  - Autoradiographic evaluation of 99mTc-methylene diphosphonate accumulation in oral
      cancer invading the mandible.
AB  - PURPOSE: Skeletal scintigraphy, a sensitive diagnostic tool used to detect
      changes in bone, is helpful for evaluating bone invasion by oral cancer. However,
      the exact sites of accumulation of 99mTc-phosphate compounds in the mandible have
      not yet been fully elucidated. The aim of this study was to determine the
      localization of 99mTc-methylene diphosphonate (MDP) in the areas of mandible that
      have been invaded by cancer. PATIENTS AND METHODS: Seven patients with oral
      cancer (lower gingiva, 4; tongue, 2; floor of the mouth, 1) who underwent
      surgical treatment with mandibular bone resection were included in the study.
      Autoradiography and contact macroradiography were used for evaluation of 99mTc
      MDP accumulation. RESULTS: Radioactivity reflecting accumulation of 99mTc-MDP was
      documented encircling the portion of the mandible with cancerous invasion,
      suggesting that 99mTc-MDP accumulated in immature bone. High uptake also was
      found in the periosteal reactive bone around the cortical bone. CONCLUSIONS: The
      amount of increased 99mTc-MDP circumscribing carcinoma invasion varies among
      cases. Additionally, uptake may not correspond directly with the amount of the
      carcinoma invasion; that seen in periosteal bone could be attributed mistakenly
      to bone invasion in planar scintigraphy.

PMID- 10077196
TI  - Arthroscopic findings in osteoarthritic temporomandibular joints.
AB  - PURPOSE: This article reports on the results of a study of the arthroscopic
      findings in the joint surfaces of osteoarthritic temporomandibular joints (TMJs).
      PATIENTS AND METHODS: Arthroscopy was performed in the upper joint compartment of
      40 TMJs in 40 patients. Thirty-one TMJs that were diagnosed with osteoarthritis
      (OA) constituted the OA group. On the basis of the presence of symptoms related
      to disc displacement and perforation, OA subgroups were defined. Nine TMJs that
      were not involved with OA constituted the control group. During the examination,
      various arthroscopic variables were recorded. Differences between groups and
      between subgroups were tested statistically. RESULTS: In the OA group, several
      arthroscopic variables were found significantly more frequently than in the
      control group. These included retrodiscal tissue redundancy, adhesions, and
      heightened attachment to the posterior wall of the glenoid fossa; articular disc
      displacement and limited mobility; and cartilage degeneration in the articular
      eminence. Moreover, in the OA group, disc displacement was found significantly
      more frequently in the period after 6 months than during the first 6 months of
      clinical signs and symptoms. Anterodiscal hypervascularity was found
      significantly more frequently during the first year than after the first year, as
      well as more during the first 2 years than after the first 2 years of clinical
      signs and symptoms, whereas a lowered attachment on the anterior slope of the
      articular eminence was found significantly more often after 2 years than during
      the first 2 years of clinical signs and symptoms. CONCLUSIONS: The findings in
      this study suggest that OA of the TMJ may initially result in synovial tissue
      hypervascularity, creeping synovitis, and redundancy, and subsequently in
      adhesion formation and a reduction of the posterior and anterior recess. Because
      of cartilage fibrillation on the articular eminence, and the subsequently reduced
      surface smoothness, the articular disc may become displaced. Eventually, disc
      mobility is limited, and adhesions and a reduced posterior and anterior recess
      prevail.

PMID- 10077197
TI  - Delayed repair of skin cancer defects.
AB  - PURPOSE: A review of surgical outcomes in 280 patients who underwent in-office
      excision of skin lesions, open wound therapy, and delayed reconstruction is
      presented. Advantages of open wound therapy and delayed reconstruction are
      discussed. PATIENTS AND METHODS: The surgical records of all patients treated
      between January 1, 1994 and December 31, 1996 were evaluated for outcome and
      complications. RESULTS: One hundred seventeen patients presented with biopsy
      confirmed malignant skin lesions of the head and neck. After surgical excision of
      the malignancy, the wounds were treated with a semiocclusive dressing while
      waiting for the results of the biopsy report and reconstruction (open wound
      therapy). Eighty-nine percent of the residual skin defects were repaired within
      10 days. The remaining 11% were closed within 35 days. Except for one allergic
      reaction to neomycin and slight blood oozing from the wound in two patients, no
      other complications occurred. CONCLUSIONS: Open wound therapy is an effective
      method for managing skin defects after excision of malignant lesions. It is cost
      effective and can be done quickly as an in-office procedure under local
      anesthesia without complications.

PMID- 10077198
TI  - Implant treatment without bone grafting in severely resorbed edentulous maxillae.
AB  - PURPOSE: This article describes the surgical technique for implant treatment in
      severely resorbed edentulous maxillae without any alveolar reconstruction before
      or combined with implant placement. PATIENTS AND MATERIAL: Fifteen patients with
      severely resorbed edentulous maxillae were treated with osseointegrated implants
      and fixed dental prostheses. All patients were initially considered to be treated
      with bone grafting because of a lack of sufficient bone volume for conventional
      treatment. Preoperative radiographic examinations showed that the height of the
      alveolar crest was on average 7.4 mm at the 4-mm-width level (Classes V to VI).
      RESULTS: By fenestration of the maxillary sinus and uncovering the nasal floor,
      the maxillary bone could be visualized and used maximally for installation of
      implants. By angulation of the implants and permitting two to five uncovered
      fixture threads on the palatal aspect, implants of optimal length could be
      installed. Eighty-six implants were placed (four to six implants in every
      patient). One implant was lost during the observation time (range, 36 to 54
      months; mean, 45 months). All patients had stable fixed prostheses at the end of
      the observation time. CONCLUSION: This cost-effective surgical technique may be
      considered as an alternative to more resource-demanding techniques such as bone
      grafting in patients with severely resorbed edentulous maxillae. However, further
      prospective comparative studies are necessary for full evaluation.

PMID- 10077199
TI  - Treatment of mandibular angle fractures with a malleable noncompression
      miniplate.
AB  - PURPOSE: This study evaluated the results in patients treated for fractures of
      the mandibular angle with a single, thin, malleable miniplate designed for use in
      the midface. PATIENTS AND METHODS: Forty-six patients with 51 fractures of the
      mandibular angle were treated by open reduction and internal fixation using one
      noncompression, thin, malleable miniplate and 1.3-mm self-threading screws placed
      through a transoral incision. No patient was placed into postsurgical
      maxillomandibular fixation. They were prospectively studied for complications.
      RESULTS: Seven patients (15.2%) experienced complications. All were considered
      minor and did not require hospitalization. Three had asymptomatic fracture of the
      bone plate, but at the time of diagnosis the fracture had already healed and it
      required no treatment. Two patients had fracture of the bone plate with continued
      fracture mobility requiring maxillomandibular fixation. Three minor infections
      occurred requiring intraoral incision and drainage. CONCLUSIONS: The use of this
      small bone plate for fractures of the angle of the mandible provided adequate
      fixation in most cases but was associated with an unacceptable incidence of plate
      fracture. However, the results also indicate that the fixation requirements for
      angle fractures is less than previously thought.

PMID- 10077200
TI  - Progressive amplification and overexpression of the eukaryotic initiation factor
      4E gene in different zones of head and neck cancers.
AB  - PURPOSE: Eukaryotic initiation factor 4E (eIF4E) binds to mRNA as the initial
      rate-limiting step in protein synthesis. Amplification and overexpression of the
      eIF4E gene has been associated with malignant transformation. The objectives of
      this study were to 1) quantify the eIF4E gene in head and neck squamous cell
      carcinoma (HNSCC) specimens, 2) quantify eIF4E protein elevation and examine its
      association with eIF4E gene amplification, and 3) determine whether there is
      progression in eIF4E gene amplification and protein overexpression in the tumor
      free resection margin, the transition zone, and the tumor core of HNSCC
      specimens. MATERIALS AND METHODS: Eighteen HNSCC specimens were divided into
      three zones: 1) tumor core; 2) transition zone; and 3) "tumor-free" margin.
      Competitive polymerase chain reaction was performed to determine eIF4E gene copy
      number. eIF4E protein expression was quantified using Western blot analysis.
      RESULTS: All 18 HNSCC specimens tested had significant eIF4E gene amplification
      (4.3+/-1.2; P < .05). In contrast, none of the 10 benign specimens from noncancer
      patients had any eIF4E gene amplification (1.1+/-0.5). In the 12 HNSCC specimens
      examined for the three zones, the tumor core and transition zone showed eIF4E
      gene amplification (5.2+/-1.1 and 3.5+/-0.9, respectively) compared with the
      "tumor-free" margin (2.1+/-1.1; P < .05). The tumor core and transition zone
      showed significant efF4E protein elevation (15.5+/-9.3, 4.4+/-4.6, respectively)
      compared with the "tumor-free" margin (0.9+/-0.5, P < .05). CONCLUSIONS: The
      eIF4E gene is amplified and overexpressed in HNSCC. Amplification and elevation
      of eIF4E were highest in the tumor core, intermediate in the transition zone, and
      lowest in the tumor-free margin. There appears to be progression of eIF4E gene
      amplification and overexpression from the "tumor-free" margin to the tumor core.

PMID- 10077201
TI  - An in vitro comparison of the effect of number and pattern of positional screws
      on load resistance.
AB  - OBJECTIVE: The purpose of this in vitro investigation was to determine whether
      the number or pattern of placement of positional screws affected their ability to
      resist vertical loads resembling mastication. MATERIALS AND METHODS: Standardized
      bone substitutes were secured with varying numbers of 17.0-mm-long, 2.0-mm outer
      diameter, self-tapping titanium screws (W. Lorenz Surgical, Jacksonville, FL) in
      various patterns using a positional screw technique. These patterns included one,
      two, three, four, and five screws in a linear pattern; two screws in a vertical
      pattern; three screws in an L-pattern, inverted-L pattern, backward-L pattern,
      inverted-backward-L pattern, and right and left diagonal pattern; four screws in
      a box pattern; and five screws in a domino pattern. Five models of each group
      were fabricated along with a control group. The models were secured in a jig and
      subjected to vertical loads by an Instron 8511.20 Mechanical Testing Unit
      (Canton, MA) until failure. Common engineering standards, including yield load,
      yield displacement, stiffness, maximum load, and displacement at maximum load,
      were measured, and means and standard deviations were derived and compared for
      statistical significance with an analysis of variance (ANOVA) and Scheffe
      multiple comparison test. RESULTS: Screw number and pattern of placement affected
      the mechanical characteristics in resistance to vertical load. Screw numbers less
      than three and all linear patterns were the least effective. The three-screw L
      patterns, as a category, provided greater resistance to vertical loads than
      either the three-screw linear or three-screw diagonal patterns. The addition of
      more than three screws in geometric patterns offered no greater benefit than the
      three-screw L patterns. CONCLUSIONS: In this in vitro study, the three-screw L
      patterns were the most effective and efficient when using the positional screw
      technique.

PMID- 10077202
TI  - Conventional surgical tracheostomy as the preferred method of airway management.

PMID- 10077203
TI  - Percutaneous dilational tracheostomy as the preferred method of airway
      management.

PMID- 10077204
TI  - Chronic mandibular pain and drainage.

PMID- 10077205
TI  - Malignant oncocytoma of the parotid gland: case report and analysis of the
      literature.

PMID- 10077206
TI  - Simultaneous mandibular distraction and arthroplasty in a patient with
      temporomandibular joint ankylosis and mandibular hypoplasia.

PMID- 10077207
TI  - Stafne cyst in an anterior location.

PMID- 10077208
TI  - Multiple odontomas of the mandible: a case report.

PMID- 10077209
TI  - Disseminated intravascular coagulation presenting as hemorrhage after tooth
      extraction.

PMID- 10077210
TI  - Congenital unilateral absence of the submandibular gland.

PMID- 10077211
TI  - Benign oncocytoma of the deep lobe of the parotid gland.

PMID- 10077212
TI  - Changing the staging of oral cancer.

PMID- 10077213
TI  - Coping with major illness.

PMID- 10077214
TI  - Staying on the cutting edge and avoiding the bleeding edge.

PMID- 10077215
TI  - Anti-tumor immunity generated by tumor cells engineered to express B7-1 via
      retroviral or adenoviral gene transfer.
AB  - We engineered B7-1 retroviral and adenoviral gene transfer systems and studied
      them in four immunogenic tumor models. M-MSV tumor cells, but not K-Balb, 38.2
      and 205 tumor cells, when expressing B7-1 by retroviral transduction were
      rejected and conferred protection against a tumor challenge. Transient expression
      of B7-1 after transduction with adenoviruses was less efficient. We observed
      enhanced cytotoxic T-lymphocyte activity accompanied by increased secretion of IL
      6, IFNgamma and GM-CSF. GM-CSF secretion correlated with tumor rejection.
      Enhanced IFNgamma but unchanged IL-4 secretion suggested a T-helper 1-mediated
      anti-tumor immune response.

PMID- 10077216
TI  - Fluorescence diagnostics and kinetic studies in the head and neck region
      utilizing low-dose delta-aminolevulinic acid sensitization.
AB  - Diagnostic measurements and pharmacokinetic studies were performed in 17 patients
      with various kinds of malignant, premalignant and benign lesions in the head and
      neck region by means of point monitoring laser-induced fluorescence. For marking
      different types of tissue, delta-aminolevulinic acid (ALA)-induced protoporphyrin
      IX (PpIX) was used. The ALA-induced PpIX synthesis was monitored at different
      time intervals after oral administration of ALA in low doses, 5 and 15 mg/kg b.w.
      Besides the porphyrin-related signal the tissue endogenous fluorescence was also
      recorded. The fluorescence spectra were evaluated at two different wavelengths
      corresponding to the specific drug-related fluorescence peak and the endogenous
      tissue fluorescence emission at 635 and 490 nm, respectively. The evaluated
      fluorescence data were correlated to the histopathological tissue investigation.
      A fall-off in the overall fluorescence intensity at 490 nm was obtained for all
      the malignant and premalignant areas, as well as an increased red fluorescence. A
      ratio between the red and the blue/green fluorescence intensity was formed for
      each time interval after the ALA administration. The lower drug dose seems to be
      sufficient to obtain a useful demarcation ratio between normal and diseased
      tissue with a very low PpIX fluorescence intensity in the normal tissue. A PpIX
      fluorescence maximum seems to occur between 3 and 4 h in normal tissues, whereas
      malignant tumour tissue shows a higher level for a longer period of time.

PMID- 10077217
TI  - Methyl bromide causes DNA methylation in rats and mice but fails to induce
      somatic mutations in lambda lacZ transgenic mice.
AB  - Following single or multiple oral treatments of rats or lambda lacZ transgenic
      mice with methyl bromide, methylated DNA adducts (N7- and/or O6-methylguanine)
      were found at comparable levels in various tissues, including among others the
      glandular stomach, the forestomach and the liver. Multiple rat treatment resulted
      in substantial decreases in the repair enzyme O6-alkylguanine-DNA
      alkyltransferase which were probably due in part to direct interaction of the
      enzyme with methyl bromide. However, no induction of mutagenesis in the lacZ
      transgene could be detected in any tissue 14 days after single treatments of up
      to 50 mg/kg or after multiple treatments of as many as 10 daily treatments of 25
      mg/kg MeBr.

PMID- 10077218
TI  - Gene amplification of human cytidine deaminase proviral cDNA and increased levels
      of its mRNA produces enhanced drug resistance to cytosine arabinoside in
      retroviral-transduced murine fibroblasts.
AB  - Hematopoietic toxicity is one of the major problems that limits the effectiveness
      of many antineoplastic drugs. One approach to overcome this problem is to confer
      chemoresistance to the hematopoietic cells by gene transfer of drug resistance
      genes. Human cytidine deaminase (CD) inactivates the cytosine nucleoside
      analogues, such as cytosine arabinoside (ARA-C), by deamination. We have reported
      previously that retroviral-mediated gene transfer of CD conferred drug resistance
      to ARA-C in murine cells. One of the major problems in the use of these vectors
      is to obtain adequate and prolonged expression of the transferred gene to produce
      a therapeutic effect in the transduced cells. The objective of this investigation
      was to determine if it is possible to increase the expression of CD proviral DNA
      in transduced murine fibroblast cells. We observed that by the use of continuous
      exposure to increasing concentrations of ARA-C it was possible to enhance drug
      resistance in the transduced cells. This drug resistance was found to be
      associated with increases in CD enzyme activity and CD proviral mRNA and by
      amplification of the proviral CD gene.

PMID- 10077219
TI  - Establishment and characterization of a second primary osteosarcoma cell line
      (OSrb/N-M) from a patient cured of bilateral retinoblastoma.
AB  - A cell line, designated OSrb/N-M, was established from the second primary
      osteosarcoma that developed in a 17-year-old Japanese female patient who had
      suffered from bilateral retinoblastoma at infancy. The OSrb/N-M cells grew as an
      adherent monolayer and retained some osteogenic biochemical phenotypes. In
      cytogenetic analyses, this cell line revealed many structural and numerical
      abnormalities, however, the bands q14 of both chromosomes 13 appeared to be
      normal, whereas the constitutional cells displayed normal female karyotypes.
      Immunoblot studies using monoclonal antibodies specific to RB protein
      demonstrated that the tumor cells did not express RB protein, suggesting that the
      OSrb/N-M cells might suffer from a loss-of-function mutation at this gene locus.
      Thus, this cell line is useful to study the molecular mechanism for the
      tumorigenesis of osteosarcoma with regard to an association with retinoblastoma.

PMID- 10077220
TI  - Antitumor activity of interleukin 12 against interleukin 2-transduced mouse
      glioma cells.
AB  - We subcutaneously inoculated parental and glioma cells genetically engineered to
      express interleukin-2 (SR/IL-2) into syngeneic mice. The tumor growth of the
      transfectants was slower than that of the parental cells. We then
      stereotactically inoculated transfectants into the brains of mice. The survival
      of the mice injected with parental cells was shorter than that of the mice
      inoculated with transfectants. SR/IL-2 cells were inoculated subcutaneously into
      the flank of mice, after which rmIL-12 was administered intraperitoneally (i.p.).
      The resultant transient tumor growth was followed by regression. rmIL-12 or
      saline were then injected i.p. into mice that had been inoculated in the brain
      with SR/IL-2 cells. There was no significant difference in survival time between
      the treated and control groups.

PMID- 10077221
TI  - Augmentation of 12-O-tetradecanoyl 13-phorbol acetate-mediated tumor promoting
      response by the porphyrin photosensitization of 7,12-dimethyl benz[a]anthracene
      initiated murine skin: role of in situ generated reactive oxygen species.
AB  - Recently, we have shown that sustained ROS generation by prolonged porphyrin
      mediated photosensitization in murine skin acts as a stage I and weak complete
      tumor promoter. Further to this, in the present study, we show that porphyrin
      photosensitization of DMBA-initiated murine skin results in the augmentation of
      TPA-mediated tumor promoting response. The photosensitization increased tumor
      yield to 15 tumors per mouse as compared to 7.5 tumors per mouse in the group
      treated with TPA alone. Further, 100% tumor incidence in the TPA-treated
      photosensitized group occurred at week 11 whereas it occurred at week 19 in the
      TPA alone treated group. Porphyrin photosensitization slightly decreased the
      latency period of TPA-mediated tumor formation by 1 week. The TPA-mediated ODC
      induction (1300% of saline-treated control) has been augmented in the
      photosensitized group (1950%). However, the amount of [3H]thymidine incorporation
      was not significantly different in the photosensitized TPA-treated and TPA alone
      treated groups. Similarly, TPA treatment in photosensitized animals augmented the
      depletion of cutaneous glutathione and enhancement of lipid peroxidation. These
      changes were attenuated in butylated hydroxytoluene-pretreated animals. Our
      results suggest that cutaneous porphyrin photosensitization augments TPA-mediated
      tumor promotion in murine skin.

PMID- 10077222
TI  - Chromosomal aberrations detected by comparative genomic hybridization (CGH) in
      human astrocytic tumors.
AB  - We investigated chromosomal aberrations in 16 patients with astrocytic tumors of
      various histologic malignancies by comparative genomic hybridization (CGH). The
      degree of chromosomal loss was shown to be negatively correlated with histologic
      malignancy. Losses of portions of chromosomes 1p, 19q and 22q were the three
      chromosomal aberrations observed most frequently. Alterations in multiple
      chromosomes were observed more frequently in glioblastomas than in astrocytomas
      or anaplastic astrocytomas (P < 0.001). Primary glioblastomas showed a high
      frequency of genomic DNA gains (5/7), whereas recurrent glioblastomas from
      anaplastic astrocytomas did not (0/3). We found CGH to be a powerful tool for
      surveying DNA alterations in tumors and characterizing the biology of tumors of
      astrocytic lineage.

PMID- 10077223
TI  - 609 C --> T polymorphism in NAD(P)H:quinone oxidoreductase gene in patients with
      prostatic adenocarcinoma or benign prostatic hyperplasia.
AB  - Allelic variations at the NQO1 locus encoding for NAD(P)H:quinone oxidoreductase
      have recently been implicated in carcinogenesis, cancer chemoprevention and
      chemotherapy. Two naturally occurring alleles differ at nucleotide position 609
      with the variant allele leading to diminished or absent enzyme activity. Using
      polymerase chain reaction-restriction fragment length polymorphic analysis, NQO1
      genotyping was performed in DNA from blood cells from 54 patients with prostatic
      adenocarcinoma, 49 patients with benign prostatic hyperplasia and 100 healthy
      control subjects. Prostatic adenocarcinoma patients and healthy controls
      demonstrated almost identical genotype distribution and frequencies of the
      variant allele (17.6 versus 17.5%). The variant allele was slightly more frequent
      in benign prostatic hyperplasia patients (23.5%). Established prostate cancer
      derived cell lines LnCAP, DU-145, and PC-3 demonstrated NQO1 wild-type genotype.
      Our study does not support the hypothesis that the variant NQO1 allele is a risk
      modifier for prostatic adenocarcinoma and/or benign prostatic hyperplasia in the
      Caucasian population.

PMID- 10077224
TI  - B-cell lymphoma of 708 cases in Japan: incidence rates and clinical prognosis
      according to the REAL classification.
AB  - New insights into the pathogenesis of lymphoid malignancies have been gained
      through novel techniques such as genetic, molecular and immunologic methods.
      Recently, based on those findings, a new classification system for lymphoid
      malignancies, known as the REAL classification, has been proposed. To clarify the
      relation between the histological classification and prognosis of B-cell lymphoid
      malignancies, we re-classified 708 cases. In all cases, the B-cell phenotype
      and/or genotype was confirmed by immunohistochemical staining and/or receptor
      gene analysis. The most common B-cell lymphoma types were diffuse large B-cell
      lymphoma (58.8%), follicular lymphoma (12.1%), marginal zone lymphoma of mucosa
      associated lymphoid tissue (MALT) (9.0%) and mantle cell lymphoma (5.9%). Minor
      types were lymphoblastic lymphoma (3.4%), Burkitt's lymphoma (2.4%), nodal
      marginal zone lymphoma (2.1%), lymphoplasmacytic lymphoma (2.0%) and plasmacytoma
      (1.4%). Rare types were prolymphocytic lymphoma and splenic marginal zone
      lymphoma. Using overall survival rates, the various B-cell lymphoma types could
      be divided into three broad groups for prognostic purposes: (1) the low risk
      group consisted of follicular lymphoma, marginal zone lymphoma of MALT, nodal
      marginal zone lymphoma, plasmacytoma and lymphoplasmacytic lymphoma; (2) the
      intermediate risk group consisted of diffuse large B-cell lymphoma, Burkitt's
      lymphoma and mantle cell lymphoma; and (3) the high risk group consisted of
      lymphoblastic lymphoma. In MALT, the low grade type had a better prognosis than
      the high grade type. In diffuse large B-cell lymphoma, the common type had a
      better prognosis than the variant type, which mainly consisted of the
      immunoblastic lymphoma. The histological classification will have a benefit for
      the clinical approach.

PMID- 10077225
TI  - Modifying effects of a mixture of acetaminophen, aspirin, dipyrone and
      ethenzamide on a multiorgan initiation model and its carcinogenicity in male F344
      rats.
AB  - Six-week-old male F344 rats were given a mixture of 0.01% diethylnitrosamine,
      0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and 0.02% N-methyl-N'-nitro-N
      nitrosoguanidine in their drinking water for 1 week. When 0.8%, 0.4%, or 0% of a
      mixture of non-steroidal anti-inflammatory drugs (NSAIDs) (acetaminophen,
      aspirin, dipyrone plus ethenzamide) was given after treatment with initiators in
      their food from weeks 2 to 68, the incidences of liver cell tumors in the rats
      were 68% (P < 0.001), 25% and 8%, respectively, but those of other tumors were
      not different. Administration of NSAIDs from weeks 2 to 104 without initiators
      showed no carcinogenicity. From the results of medium-term liver bioassay, it was
      suggested that dipyrone and ethenzamide had promoting effects and acetaminophen
      had an inhibitory effect on rat hepatocarcinogenesis.

PMID- 10077226
TI  - Levels of expression of pleiotrophin and protein tyrosine phosphatase zeta are
      decreased in human colorectal cancers.
AB  - Pleiotrophin (PTN) and midkine (MK) form a distinct family of heparin binding
      growth factors. In a variety of human cancers, MK mRNA levels have been found to
      be increased as compared to adjacent non-cancerous tissues. We examined the
      expression of PTN, its putative receptor, namely protein tyrosine phosphatase
      zeta (PTPzeta, also known as RPTPbeta), and a related protein, receptor-type
      protein tyrosine phosphatase gamma (RPTPgamma), in human colorectal cancers and
      the adjacent normal mucosae. PTN and PTPzeta mRNA levels were generally decreased
      in colorectal cancers as compared to those in adjacent normal mucosae, while the
      RPTPzeta level was not significantly different between them.

PMID- 10077227
TI  - The study of innate drug resistance of human hepatocellular carcinoma Bel7402
      cell line.
AB  - The innate drug resistance of human hepatocellular carcinoma (HCC) Bel7402 cell
      line was studied in vitro. MTT assay showed that Bel7402 cells were innately
      resistant to doxorubicin (Dox), and even more resistant to vincristine (VCR).
      This resistance could be effectively reversed by verapamil (Ver), one of the
      classical multidrug resistance (MDR) modulating agents. However, the differences
      in 5-fluorouracil (5-FU) toxicity between these two cell lines is much less and
      the resistance of Bel7402 cells could only be slightly reversed by Ver, which may
      be experimental noise. Immunocytochemical staining using anti-p-glycoprotein
      monoclonal antibody JSB-1 indicated that the expression of the P-glycoprotein (P
      gp) in the innate Bel7402 cells was elevated compared with the sensitive KB
      cells. The accumulation of Dox in innate resistant Bel7402 cells was 50.7% lower
      than that in sensitive KB cells by using spectrofluometric analyses, and the
      accumulation of Dox increased 1.6 fold in Bel7402 cells in the presence of Ver.
      The susceptibility of Dox-induced apoptosis was also increased in the presence of
      Ver by using flow cytometric assay and DNA fragmentation quantitative assay as
      well as by Hoechst 33258 staining. It appears that the innate Bel7402 cells might
      be useful in screening new antitumour drugs or new chemosensitisers which could
      overcome the innate or acquired resistant mechanism, and the toxicity and
      reversal effects with 5-FU are different from those known to be P-gp substrates
      such as VCR, Dox, and taxol.

PMID- 10077228
TI  - Antisense oligonucleotides to gastrin inhibit growth of human pancreatic cancer.
AB  - Human pancreatic cancer is stimulated by the autocrine production of gastrin. In
      this study, the effects of administration of antisense oligonucleotides to
      gastrin on growth of pancreatic cancer were evaluated in vitro and in vivo. Log
      phase BxPC-3 human pancreatic cancer cells in culture were exposed to increasing
      concentrations (0.5-10 microM) of a synthetic 20-mer antisense phosphorothioate
      oligonucleotide to gastrin for 48 h and growth was assessed by the cellular
      proliferation assay. Growth was inhibited up to 88% by anti-gastrin
      oligonucleotides in a dose-related fashion compared to cells treated with diluent
      or a randomized sequence with the same composition as the anti-gastrin
      oligonucleotide. In vivo nude mice bearing BxPC-3 xenografts were treated daily
      for 14 days with a 0.1-ml intratumoral injection of either anti-gastrin (5
      microM), the scrambled sequence control phosphorothioate oligonucleotide (5
      microM), or buffer. Tumors from the anti-gastrin-treated mice were significantly
      smaller in volume and weight and had less gastrin detected by radioimmunoassay
      than either controls. These results support the role of gastrin as a stimulatory
      peptide for growth of human pancreatic cancer. Antisense oligonucleotide to
      gastrin may have a role in the future treatment of patients with pancreatic
      cancer.

PMID- 10077229
TI  - Enhancement of glucuronosyl etoposide transport by glutathione in multidrug
      resistance-associated protein-overexpressing cells.
AB  - Multidrug resistance-associated protein (MRP) has been shown to transport
      glutathione (GSH) S-conjugates such as leukotriene C4 (LTC4) and S-(2,4
      dinitrophenyl)-glutathione (DNP-SG). On the other hand, it has while it has been
      reported that MRP-overexpressing cells exhibit decreased sensitivity to drugs
      which do not form GSH S-conjugates. In this study, we found that GSH affects the
      transport of glucuronosyl etoposide as a major metabolite of etoposide in MRP
      overexpressing KB/VP-4 cells. The relative resistance level of KB/VP-4 cells to
      etoposide was 70-fold that of wild-type KB cells. Membrane vesicles prepared from
      KB/VP-4 cells exhibited markedly enhanced ATP-dependent transport of glucuronosyl
      etoposide as well as LTC4. Transport of glucuronosyl etoposide was augmented in
      the presence of GSH. Treatment of KB/VP-4 cells with buthionine sulfoximine
      (BSO), an inhibitor of GSH synthesis, resulted in about 75% depletion of cellular
      GSH levels, a four-fold increase of the sensitivity to etoposide and depression
      of glucuronosyl etoposide efflux. These results suggest that GSH plays a role in
      the enhancement of MRP-mediated glucuronosyl etoposide transport.

PMID- 10077230
TI  - Secretory pathways in endothelin synthesis.

PMID- 10077231
TI  - Pharmacological characterization of beta2-adrenoceptor in PGT-beta mouse pineal
      gland tumour cells.
AB  - 1. The adrenoceptor in a mouse pineal gland tumour cell line (PGT-beta) was
      identified and characterized using pharmacological and physiological approaches.
      2. Adrenaline and noradrenaline, adrenoceptor agonists, stimulated cyclic AMP
      generation in a concentration-dependent manner, but had no effect on inositol
      1,4,5-trisphosphate production. Adrenaline was a more potent activator of cyclic
      AMP generation than noradrenaline, with half maximal-effective concentrations
      (EC50) seen at 175+/-22 nM and 18+/-2 microM for adrenaline and noradrenaline,
      respectively. 3. The addition of forskolin synergistically stimulated the
      adrenaline-mediated cyclic AMP generation in a concentration-dependent manner. 4.
      The pA2 value for the specific beta2-adrenoceptor antagonist ICI-118,551 (8.7+/
      0.4) as an antagonist of the adrenaline-stimulated cyclic AMP generation were 3
      units higher than the value for the betaI-adrenoceptor antagonist atenolol (5.6+/
      0.3). 5. Treatment of the cells with adrenaline and forskolin evoked a 3 fold
      increase in the activity of serotonin N-acetyltransferase with the peak occurring
      6 h after stimulation. 6. These results suggest the presence of beta2
      adrenoceptors in mouse pineal cells and a functional relationship between the
      adenylyl cyclase system and the regulation of N-acetyltransferase expression.

PMID- 10077232
TI  - Beneficial effects of raxofelast (IRFI 016), a new hydrophilic vitamin E-like
      antioxidant, in carrageenan-induced pleurisy.
AB  - 1. Peroxynitrite is a strong oxidant that results from reaction between NO and
      superoxide. It has been recently proposed that peroxynitrite plays a pathogenetic
      role in inflammatory processes. Here we have investigated the therapeutic
      efficacy of raxofelast, a new hydrophilic vitamin E-like antioxidant agent, in
      rats subjected to carrageenan-induced pleurisy. 2. In vivo treatment with
      raxofelast (5, 10, 20 mg kg(-1) intraperitoneally 5 min before carrageenan)
      prevented in a dose dependent manner carrageenan-induced pleural exudation and
      polymorphonuclear migration in rats subjected to carrageenan-induced pleurisy.
      Lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, as well as
      histological organ injury were significantly reduced by raxofelast. 3.
      Immunohistochemical analysis for nitrotyrosine, a footprint of peroxynitrite,
      revealed a positive staining in lungs from carrageenan-treated rats. No positive
      nitrotyrosine staining was found in the lungs of the carrageenan-treated rats,
      which received raxofelast (20 mg kg 1) treatment. 4. Furthermore, in vivo
      raxofelast (5, 10, 20 mg kg(-1)) treatment significantly reduced peroxynitrite
      formation as measured by the oxidation of the fluorescent dihydrorhodamine 123,
      prevented the appearance of DNA damage, the decrease in mitochondrial respiration
      and partially restored the cellular level of NAD+ in ex vivo macrophages
      harvested from the pleural cavity of rats subjected to carrageenan-induced
      pleurisy. 5. In conclusion, our study demonstrates that raxofelast, a new
      hydrophilic vitamin E-like antioxidant agent, exerts multiple protective effects
      in carrageenan-induced acute inflammation.

PMID- 10077233
TI  - Specific inhibition of ADP-induced platelet aggregation by clopidogrel in vitro.
AB  - 1. The thienopyridine clopidogrel is a specific inhibitor of ADP-induced platelet
      aggregation ex vivo. No direct effects of clopidogrel (< or = 100 microM) on
      platelet aggregation in vitro have been described so far. 2. Possible in vitro
      antiaggregatory effects (turbidimetry) of clopidogrel were studied in human
      platelet-rich plasma and in washed platelets. 3. Incubation of platelet-rich
      plasma with clopidogrel (< or = 100 microM) for up to 8 h did not result in any
      inhibition of ADP (6 microM)-induced platelet aggregation. 4. Incubation of
      washed platelets with clopidogrel resulted in a time- (maximum effects after 30
      min) and concentration-dependent (IC50 1.9+/-0.3 microM) inhibition of ADP (6
      microM)-induced platelet aggregation. Clopidogrel (30 microM) did not inhibit
      collagen (2.5 microg ml(-1))-, U46619 (1 microM)- or thrombin (0.1 u ml(-1))
      induced platelet aggregation. The inhibition of ADP-induced aggregation by
      clopidogrel (30 microM) was insurmountable indicating a non-equilibrium
      antagonism of ADP actions. The R enantiomer SR 25989 C (30 microM) was
      significantly less active than clopidogrel (30 microM) in inhibiting platelet
      aggregation (32+/-5% vs 70+/-1% inhibition, P < 0.05, n = 5). 5. In washed
      platelets, clopidogrel (< or = 30 microM) did not significantly reverse the
      inhibition of prostaglandin E1 (1 microM)-induced platelet cyclic AMP formation
      by ADP (6 microM). 6. The antiaggregatory effects of clopidogrel were unchanged
      when the compound was removed from the platelet suspension. However, platelet
      inhibition by clopidogrel was completely abolished when albumin (350 mg ml(-1))
      was present in the test buffer. 7. It is concluded that clopidogrel specifically
      inhibits ADP-induced aggregation of washed platelets in vitro without hepatic
      bioactivation. Inhibition of ADP-induced platelet aggregation by clopidogrel in
      vitro occurs in the absence of measurable effects on the reversal of PGE1
      stimulated cyclic AMP by ADP.

PMID- 10077234
TI  - Endothelium-dependent hyperpolarization in resting and depolarized mammary and
      coronary arteries of guinea-pigs.
AB  - 1. The membrane potential responses in guinea-pig coronary and mammary arteries
      attributable to endothelium-derived nitric oxide (NO), prostaglandin (PG) and
      hyperpolarizing factor (EDHF), and to exogenous NO and the prostacyclin analogue,
      iloprost, were compared at rest and when depolarized with the thromboxane
      analogue, U46619. 2. In the coronary artery, stimulation of the endothelium with
      acetylcholine (ACh) evoked hyperpolarization attributable to NO and a PG with
      similar pD2s at rest and in the presence of U46619. However, in depolarized
      tissues, the pD2 of the response attributed to EDHF required a 10 fold lower
      concentration of ACh compared with at rest. 3. In the mammary artery, lower
      concentrations of ACh were required to evoke NO- and EDHF-dependent
      hyperpolarizations in depolarized mammary artery compared with at rest, while PG
      dependent hyperpolarization did not occur until the concentration of ACh was
      increased some 10 fold both at rest and in U46619. 4. The smooth muscle of the
      coronary artery of guinea-pigs was some 4 fold more sensitive to exogenous NO and
      iloprost than was the mammary artery. 5. In conclusion, the membrane potential
      response in arteries at rest, that is, in the absence of constrictor, may be
      extrapolated to events in the presence of constrictor when NO and PG are under
      study. However, the sensitivity to ACh and the magnitude of the hyperpolarization
      attributed to EDHF obtained in tissues at rest may underestimate these parameters
      in depolarized tissues.

PMID- 10077235
TI  - Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons.
AB  - 1. The aim of our study is to clarify the relationship between expression pattern
      of P2X receptors and the cell type of male adult rat (Wistar) dorsal root
      ganglion (DRG) neurons. We identified the nociceptive cells of acutely
      dissociated DRG neurons from adult rats type using capsaicin sensitivity. 2. Two
      types of ATP-activated currents, one with fast, the other with slow
      desensitization, were found under voltage-clamp conditions. In addition, cells
      with fast but not slow desensitization responded to capsaicin, indicating that
      there was a relationship between current kinetics and capsaicin-sensitivity. 3.
      Both types of neurons were responsive to ATP and alpha, beta methylene-ATP
      (alpha,betameATP). The concentration of alpha,(beta)meATP producing half-maximal
      activation (EC50) of neurons with fast desensitization was less (11 microM) than
      that of neurons with slow desensitization (63 microM), while the Hill
      coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'
      disulphonic acid tetrasodium (PPADS) antagonized alpha,betameATP-induced currents
      in both types of neurons. 4. In situ hybridization revealed that small cells of
      the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed
      mRNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large
      cells of the DRG. 5. These results suggest that capsaicin-sensitive, small-sized
      DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin
      insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor
      with P2X2 and P2X3.

PMID- 10077236
TI  - Characterization of alpha1-adrenoceptor subtypes mediating vasoconstriction in
      human umbilical vein.
AB  - 1. The present study attempted to characterize pharmacologically the subtypes of
      alpha-adrenoceptors mediating contractions in human umbilical vein (HUV). 2. HUV
      rings were mounted in isolated organ baths and cumulative concentration-response
      curves were constructed for the alpha-adrenoceptor agonists phenylephrine and
      adrenaline. Adrenaline was more potent than phenylephrine (pD2=7.29 and 6.04
      respectively). 3. Isoproterenol exhibited no agonism on KCl pre-contracted HUV
      rings. Propranolol (1 microM) and rauwolscine (0.1 microM) did not affect the
      concentration-response curves to adrenaline. These results demonstrate the lack
      of involvement of functional beta-or alpha2-adrenoceptors in adrenaline-induced
      vasoconstriction. 4. The non subtype selective alpha1-adrenoceptor antagonist
      prazosin was evaluated on phenylephrine and adrenaline concentration-response
      curves. The effects of the competitive alpha1A and alpha1D-adrenoceptor
      antagonists, 5-methyl urapidil and BMY 7378 and the irreversible alpha1B
      selective compound chloroethylclonidine (CEC) were also evaluated on adrenaline
      concentration-response curves. 5. The potencies of prazosin against responses
      mediated by adrenaline (pA2= 10.87) and phenylephrine (pA2= 10.70) indicate the
      involvement of prazosin-sensitive functional alpha1-adrenoceptor subtype in
      vasoconstriction of the HUV. 6. The potencies of 5-methyl urapidil (pA2 = 6.70)
      and BMY 7378 (pA2= 7.34) were not consistent with the activation of an alpha1A-
      or alpha1D-adrenoceptor population. 7. Exposure to a relatively low CEC
      concentration (3 microM) abolished the maximum response to adrenaline suggesting
      that this response was mediated by an alpha1B-adrenoceptor subtype. 8. We
      conclude that HUV express a prazosin-sensitive functional alpha1-adrenoceptor
      resembling the alpha1B-subtype according with the low pA2 values for both 5
      methyl urapidil and BMY 7378 and the high sensitivity to CEC.

PMID- 10077237
TI  - Endothelin receptor expression and pharmacology in human saphenous vein graft.
AB  - 1. We have investigated the expression and pharmacology of endothelin (ET)
      receptors in human aortocoronary saphenous vein grafts. 2. Subtype-selective
      ligands were used to autoradiographically identify ET(A) ([125I]-PD151242) and
      ET(B)([125I]-BQ3020) receptors. In graft saphenous vein ETA receptors
      predominated in the media, with few ET(B) receptors identified. Neither subtype
      was detected in the thickened neointima. 3. The ratio of medial ET(A):ET(B)
      receptors was 75%: 25% in both graft and control saphenous vein. 4. ET-1
      contracted control (EC50 2.9 nM) and graft (EC50 4.5 nM) saphenous vein more
      potently than diseased coronary artery (EC50 25.5 nM). 5. In all three blood
      vessels ET-1 was 100 times more potent than ET-3 and three times more potent than
      sarafotoxin 6b (S6b). Little or no response was obtained in any vessel with the
      ET(B) agonist sarafotoxin 6c (S6c). 6. The ET(A) antagonist PD156707 (100 nM)
      blocked ET-1 responses in all three vessels with pKb values of approximately 8.0.
      7. For individual graft veins the EC50 value for ET-1 and 'age' of graft in years
      showed a significant negative correlation. 8. In conclusion there is no
      alteration in ET receptor expression in the media of saphenous veins grafted into
      the coronary circulation compared to control veins. ETA receptors predominantly
      mediate the vasoconstrictor response to ET-1 in graft vein, with no apparent up
      regulation of ET(B) receptors. The sensitivity of the graft vein to ET-1
      increased with graft 'age', suggesting that these vessels may be particularly
      vulnerable to the increased plasma ET levels that are detected in patients with
      cardiovascular disease.

PMID- 10077238
TI  - Absence of G-protein activation by mu-opioid receptor agonists in the spinal cord
      of mu-opioid receptor knockout mice.
AB  - 1. The ability of mu-opioid receptor agonists to activate G-proteins in the
      spinal cord of mu-opioid receptor knockout mice was examined by monitoring the
      binding to membranes of the non-hydrolyzable analogue of GTP, guanosine-5'-O-(3
      [35S]thio)triphosphate ([35S]GTPgammaS). 2. In the receptor binding study,
      Scatchard analysis of [3H][D-Ala2,NHPhe4,Gly-ol]enkephalin ([3H]DAMGO; mu-opioid
      receptor ligand) binding revealed that the heterozygous mu-knockout mice
      displayed approximately 40% reduction in the number of mu-receptors as compared
      to the wild-type mice. The homozygous mu-knockout mice showed no detectable mu
      binding sites. 3. The newly isolated mu-opioid peptides endomorphin-1 and -2, the
      synthetic selective mu-opioid receptor agonist DAMGO and the prototype of mu
      opioid receptor agonist morphine each produced concentration-dependent increases
      in [35S]GTPgammaS binding in wild-type mice. This stimulation was reduced by 55
      70% of the wild-type level in heterozygous, and virtually eliminated in
      homozygous knockout mice. 4. No differences in the [35S]GTPgammaS binding
      stimulated by specific delta1- ([D-Pen2,5]enkephalin), delta2-([D-Ala2]deltorphin
      II) or kappa1-(U50,488H) opioid receptor agonists were noted in mice of any of
      the three genotypes. 5. The data clearly indicate that mu-opioid receptor gene
      products play a key role in G-protein activation by endomorphins, DAMGO and
      morphine in the mouse spinal cord. They support the idea that mu-opioid receptor
      densities could be rate-limiting steps in the G-protein activation by mu-opioid
      receptor agonists in the spinal cord. These thus indicate a limited physiological
      mu-receptor reserve. Furthermore, little change in delta1-, delta2- or kappa1
      opioid receptor-G-protein complex appears to accompany mu-opioid receptor gene
      deletions in this region.

PMID- 10077239
TI  - Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic
      cardiovascular regulation.
AB  - 1. The aim of the present study was to analyse the cardiovascular actions of the
      synthetic CB1/CB2 cannabinoid receptor agonist WIN55212-2, and specifically to
      determine its sites of action on sympathetic cardiovascular regulation. 2. Pithed
      rabbits in which the sympathetic outflow was continuously stimulated electrically
      or which received a pressor infusion of noradrenaline were used to study
      peripheral prejunctional and direct vascular effects, respectively. For studying
      effects on brain stem cardiovascular regulatory centres, drugs were administered
      into the cisterna cerebellomedullaris in conscious rabbits. Overall
      cardiovascular effects of the cannabinoid were studied in conscious rabbits with
      intravenous drug administration. 3. In pithed rabbits in which the sympathetic
      outflow was continuously electrically stimulated, intravenous injection of
      WIN55212-2 (5, 50 and 500 microg kg(-1)) markedly reduced blood pressure, the
      spillover of noradrenaline into plasma and the plasma noradrenaline
      concentration, and these effects were antagonized by the CB1 cannabinoid receptor
      selective antagonist SR141716A. The hypotensive and the sympathoinhibitory effect
      of WIN55212-2 was shared by CP55940, another mixed CB1/CB2 cannabinoid receptor
      agonist, but not by WIN55212-3, the enantiomer of WIN55212-2, which lacks
      affinity for cannabinoid binding sites. WIN55212-2 had no effect on vascular tone
      established by infusion of noradrenaline in pithed rabbits. 4. Intracisternal
      application of WIN55212-2 (0.1, 1 and 10 microg kg(-1)) in conscious rabbits
      increased blood pressure and the plasma noradrenaline concentration and elicited
      bradycardia; this latter effect was antagonized by atropine. 5. In conscious
      animals, intravenous injection of WIN55212-2 (5 and 50 microg kg(-1)) caused
      bradycardia, slight hypotension, no change in the plasma noradrenaline
      concentration, and an increase in renal sympathetic nerve firing. The highest
      dose of WIN55212-2 (500 microg kg(-1)) elicited hypotension and tachycardia, and
      sympathetic nerve activity and the plasma noradrenaline concentration declined.
      6. The results obtained in pithed rabbits indicate that activation of CB1
      cannabinoid receptors leads to marked peripheral prejunctional inhibition of
      noradrenaline release from postganglionic sympathetic axons. Intracisternal
      application of WIN55212-2 uncovered two effects on brain stem cardiovascular
      centres: sympathoexcitation and activation of cardiac vagal fibres. The highest
      dose of systemically administered WIN55212-2 produced central sympathoinhibition;
      the primary site of this action is not known.

PMID- 10077240
TI  - Effects of vanadium complexes with organic ligands on glucose metabolism: a
      comparison study in diabetic rats.
AB  - 1. Vanadium compounds can mimic actions of insulin through alternative signalling
      pathways. The effects of three organic vanadium compounds were studied in non
      ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3
      ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple
      inorganic vanadium salt, vanadyl sulphate (VS) was also studied. 2. Oral
      administration of the three organic vanadium compounds (125 mg vanadium element
      1(-1) in drinking fluids) for up to 3 months induced a faster and larger fall in
      glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a
      glucose load were improved accordingly. 3. Activities and mRNA levels of key
      glycolytic enzymes (glucokinase and L-type pyruvate kinase) which are suppressed
      in the diabetic liver, were restored by vanadium treatment. The organic forms
      showed greater efficacy than VS, especially VAc. 4. VAc rats exhibited the
      highest levels of plasma or tissue vanadium, most likely due to a greater
      intestinal absorption. However, VAc retained its potency when given as a single
      i.p. injection to diabetic rats. Moreover, there was no relationship between
      plasma or tissue vanadium levels and any parameters of glucose homeostasis and
      hepatic glucose metabolism. Thus, these data suggest that differences in potency
      between compounds are due to differences in their insulin-like properties. 5.
      There was no marked toxicity observed on hepatic or renal function. However,
      diarrhoea occurred in 50% of rats chronically treated with VS, but not in those
      receiving the organic compounds. 6. In conclusion, organic vanadium compounds, in
      particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of
      diabetic rats more safely and potently than VS. This is not simply due to
      improved intestinal absorption, indicating more potent insulin-like properties.

PMID- 10077241
TI  - Bronchoconstrictor effect of thrombin and thrombin receptor activating peptide in
      guinea-pigs in vivo.
AB  - 1. Several thrombin cellular effects are dependent upon stimulation of proteinase
      activated receptor-1 (PAR-1) localized over the cellular surface. Following
      activation by thrombin, a new N-terminus peptide is unmasked on PAR-1 receptor,
      which functions as a tethered ligand for the receptor itself. Synthetic peptides
      called thrombin receptor activating peptides (TRAPs), corresponding to the N
      terminus residue unmasked, reproduce several thrombin cellular effects, but are
      devoid of catalytic activity. We have evaluated the bronchial response to
      intravenous administration of human alpha-thrombin or a thrombin receptor
      activating peptide (TRAP-9) in anaesthetized, artificially ventilated guinea
      pigs. 2. Intravenous injection of thrombin (100 microkg(-1)) caused
      bronchoconstriction that was recapitulated by injection of TRAP-9 (1 mg kg(-1)).
      Animal pretreatment with the thrombin inhibitor Hirulog (10 mg kg(-1) i.v.)
      prevented thrombin-induced bronchoconstriction, but did not affect
      bronchoconstriction induced by TRAP-9. Both agents did not induce
      bronchoconstriction when injected intravenously to rats. 3. The
      bronchoconstrictor effect of thrombin and TRAP-9 was subjected to tolerance;
      however, in animals desensitized to thrombin effect, TRAP-9 was still capable of
      inducing bronchoconstriction, but not vice versa. 4. Depleting animals of
      circulating platelets prevented bronchoconstriction induced by both thrombin and
      TRAP-9. 5. Bronchoconstriction was paralleled by a biphasic change in arterial
      blood pressure, characterized by a hypotensive phase followed by a hypertensive
      phase. Thrombin-induced hypotension was not subject to tolerance and was
      inhibited by Hirulog; conversely, hypertension was subject to tolerance and was
      not inhibited by Hirulog. Hypotension and hypertension induced by TRAP-9 were
      neither subject to tolerance nor inhibited by Hirulog. 6. Our results indicate
      that thrombin causes bronchoconstriction in guinea-pigs through a mechanism that
      requires proteolytic activation of its receptor and the exposure of the tethered
      ligand peptide. Platelet activation might be triggered by the thrombin effect.

PMID- 10077242
TI  - Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the
      anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation.
AB  - 1. The effects of intravenous administration of endothelin (ET) receptor
      antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg
      kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve
      ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of
      the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(
      1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion
      stimulation produced frequency related increases in carotid blood flow,
      reductions in carotid vascular resistance and non-frequency related increases in
      blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve
      ganglion-induced increases in blood pressure but had no effect on changes in
      carotid flow or resistance. Maximal reductions in carotid vascular resistance was
      observed at 10 Hz, and this frequency was selected to investigate the effects of
      drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine
      treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no
      effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced
      a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3)
      produced a 30% reduction in carotid vascular resistance. Sumatriptan produced
      dose-related reductions in resting carotid flow and increases (max. 104% at 0.3
      mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3)
      and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation
      induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8
      37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor
      blockade attenuates the vasodilator effects of trigeminal nerve ganglion
      stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized
      cats.

PMID- 10077243
TI  - Role of K+ channels in A2A adenosine receptor-mediated dilation of the
      pressurized renal arcuate artery.
AB  - 1. Adenosine A2A receptor-mediated renal vasodilation was investigated by
      measuring the lumenal diameter of pressurized renal arcuate arteries isolated
      from the rabbit. 2. The selective A2A receptor agonist CGS21680 dilated the
      arteries with an EC50 of 130 nM. The CGS21680-induced vasodilation was, on
      average, 34% less in endothelium-denuded arteries. 3. The maximum response and
      the EC50 for CGS21680-induced vasodilation in endothelium-intact arteries were
      not significantly affected by incubation with the K+ channel blockers apamin (100
      nM), iberiotoxin (100 nM), 3,4-diaminopyridine (1 mM), glibenclamide (1 microM)
      or Ba2+ (10 microM). However, a cocktail mixture of these blockers did
      significantly inhibit the maximum response by almost 40%, and 1 mM Ba2+ alone or
      1 mM Ba2+ in addition to the cocktail inhibited the maximum CGS21680-response by
      58% and about 75% respectively. 4. CGS21680-induced vasodilation was strongly
      inhibited when the extracellular K+ level was raised to 20 mM even though the
      dilator response to 1 microM levcromakalim, a K(ATP) channel opener drug, was
      unaffected. 5. CGS21680-induced vasodilation was inhibited by 10 microM ouabain,
      an inhibitor of Na+/K(+)-ATPase, but ouabain had a similar inhibitory effect on
      vasodilation induced by 30 nM nicardipine (a dihydropyridine Ca2+ antagonist) or
      1 microM levcromakalim. 6. The data suggest that K+ channel activation does play
      a role in A(2A) receptor-mediated renal vasodilation. The inhibitory effect of
      raised extracellular K+ levels on the A(2A) response may be due to K(+)-induced
      stimulation of Na+/K(+)-ATPase.

PMID- 10077244
TI  - Modification of left ventricular hypertrophy by chronic etomixir treatment.
AB  - 1. Etomoxir (2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), an irreversible
      carnitine palmitoyl-transferase 1 inhibitor, reduces the expression of the
      myocardial foetal gene programme and the functional deterioration during heart
      adaption to a pressure-overload. Etomoxir may, however, also improve the
      depressed myocardial function of hypertrophied ventricles after a prolonged
      pressure overload. 2. To test this hypothesis, we administered racemic etomoxir
      (15 mg kg(-1) day(-1) for 6 weeks) to rats with ascending aortic constriction
      beginning 6 weeks after imposing the pressure overload. 3. The right
      ventricular/body weight ratio increased (P<0.05) by 20% in etomoxir treated rats
      (n = 10) versus untreated rats with ascending aortic constriction (n = 10). Left
      ventricular weight was increased (P<0.05) by 8%. Etomoxir blunted the increase in
      left ventricular chamber volume. Etomoxir raised the proportion of V1 isomyosin
      (35+/-4% versus 24+/-2%; P<0.05) and decreased the percentage of V3 isomyosin
      (36+/-4% versus 48+/-3%; P<0.05). 4. Maximum isovolumically developed pressure
      was higher in etomoxir treated rats than in untreated pressure overloaded rats
      (371+/-22 versus 315+/-23 mmHg; P<0.05). Maximum rates of ventricular pressure
      development (14,800+/-1310 versus 12,340+/-1030mmHg s(-1); P<0.05) and decline
      (6440+/-750 versus 5040+/-710 mmHg s(-1); P<0.05) were increased as well.
      Transformation of pressure values to ventricular wall stress data revealed an
      improved myocardial function which could partially account for the enhanced
      function of the whole left ventricle. 5. The co-ordinated action of etomoxir on
      ventricular mass, geometry and myocardial phenotype enhanced thus the pressure
      generating capacity of hypertrophied pressure-overloaded left ventricles and
      delayed the deleterious dilative remodelling.

PMID- 10077245
TI  - Block by fluoxetine of volume-regulated anion channels.
AB  - 1. We have used the whole-cell patch clamp technique to study the effect of
      fluoxetine, a commonly used antidepressant drug, on the volume-regulated anion
      channel (VRAC) in calf pulmonary artery endothelial (CPAE) cells. We also
      examined its effects on other Cl- channels, i.e. the Ca2(+)-activated Cl- current
      (I(Cl,Ca) and the cystic fibrosis transmembrane conductance regulator (CFTR) to
      assess the specificity of this compound for VRAC. 2. At pH 7.4 fluoxetine induced
      a fast and reversible block of the volume-sensitive chloride current
      (I(Cl,swell)), with a Ki value of 6.0+/-0.5 microM (n = 6-9). The blocking
      efficiency increased with increasing extracellular pH (Ki= 0.32+/-0.01 microM at
      pH 8.8, n = 3-9), indicating that the blockade is mediated by the uncharged form
      of fluoxetine. 3. Fluoxetine inhibited Ca2(+)-activated Cl(-) currents, I(Cl,Ca),
      activated by loading CPAE cells via the patch pipette with 1000 nM free Ca2+ (Ki=
      10.7+/-1.6 microm at pH 7.4, n=3-5). The CFTR channel, transiently transfected in
      CPAE cells, was also inhibited with a Ki value of 26.9+/-9.4 microM at pH 7.4 (n
      = 3). 4. This study describes for the first time the effects of fluoxetine on
      anion channels. Our data reveal a potent block of VRAC at fluoxetine
      concentrations close to plasma concentrations. The results suggest a hydrophobic
      interaction with high affinity between uncharged fluoxetine and volume-activated
      chloride channels. Ca(2+)-activated Cl- currents and CFTR are also blocked by
      fluoxetine, revealing a novel characteristic of the drug as a chloride channel
      modulator.

PMID- 10077246
TI  - Endogenous nitric oxide in the maintenance of rat microvascular integrity against
      widespread plasma leakage following abdominal laparotomy.
AB  - 1. The role of nitric oxide (NO) in the maintenance of microvascular integrity
      during minor surgical manipulation has been evaluated in the rat. 2. The NO
      synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1), s.c.)
      and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg kg(-1), s.c.) had no effect on
      microvascular leakage of radiolabelled albumin over 1 h in the stomach, duodenum,
      jejunum, colon, lung and kidney in the un-operated conscious or pentobarbitone
      anaesthetized rat. 3. In contrast, in anaesthetized rats with a midline abdominal
      laparotomy (5 cm), L-NAME (1-5 mg kg(-1), s.c.) or L-NMMA (12.5-50 mg kg(-1),
      s.c.) dose-dependently increased gastrointestinal, renal and pulmonary vascular
      leakage, effects reversed by L-arginine pretreatment (300 mg kg(-1), s.c., 15
      min). These actions were not observed in anaesthetized rats that had only
      received a midline abdominal skin incision (5 cm). 4. Pretreatment with a rabbit
      anti-rat neutrophil serum (0.4 ml kg(-1), i.p.), 4 h before laparotomy, abolished
      the plasma leakage induced by L-NAME in all the organs investigated. 5. These
      results indicate that the following abdominal laparotomy, inhibition of
      constitutive NO synthase provokes vascular leakage in the general
      microcirculation, by a process that may involve neutrophils. Such effects could
      thus confound studies on the microvascular actions of NO synthase inhibitors
      using acute surgically prepared in vivo models. The findings thus suggest that
      constitutively-formed NO has a crucial role in the maintenance of acute
      microvascular integrity following abdominal surgical intervention.

PMID- 10077247
TI  - Neurogenic plasma leakage in mouse airways.
AB  - 1. This study sought to determine whether neurogenic inflammation occurs in the
      airways by examining the effects of capsaicin or substance P on microvascular
      plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. 2.
      Single bolus intravenous injections of capsaicin (0.5 and 1 micromol kg(-1),
      i.v.) or substance P (1, 10 and 37 nmol kg(-10, i.v.) failed to induce
      significant leakage in the trachea, assessed as extravasation of Evans blue dye,
      but did induce leakage in the urinary bladder and skin. 3. Pretreatment with
      captopril (2.5 mg kg(-1), i.v.), a selective inhibitor of angiotensin converting
      enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg(-1),
      i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline
      leakage of Evans blue in the absence of any exogenous inflammatory mediator. The
      increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg
      kg(-1), i.v.). 4. After pretreatment with phosphoramidon and captopril, capsaicin
      increased the Evans blue leakage above the baseline in the trachea, but not in
      the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist
      SR 140333 (0.7 mg kg(-1), i.v.), but not by the NK2 receptor antagonist SR 48968
      (1 mg kg(-1), i.v.). 5. Experiments using Monastral blue pigment as a tracer
      localized the leakage to postcapillary venules in the trachea and intrapulmonary
      bronchi, although the labelled vessels were less numerous in mice than in
      comparably treated rats. Blood vessels of the pulmonary circulation were not
      labelled. 6. We conclude that neurogenic inflammation can occur in airways of
      pathogen-free mice, but only after the inhibition of enzymes that normally
      degrade inflammatory peptides. Neurogenic inflammation does not involve the
      pulmonary microvasculature.

PMID- 10077248
TI  - Modulation of ET-1-induced contraction of human bronchi by airway epithelium
      dependent nitric oxide release via ET(A) receptor activation.
AB  - 1. The purpose of this work was to investigate whether endothelin-1 (ET-1) was
      able to induce the release of an inhibitory factor from the airway epithelium in
      isolated human bronchi and to identify this mediator as well as the endothelin
      receptor involved in this phenomenon. 2. In intact bronchi, ET-1 induced a
      concentration-dependent contraction (-logEC50 = 7.92+/-0.09, n = 18) which was
      potentiated by epithelium removal (-logEC50 = 8.65+/-0.11, n = 17). BQ-123 , an
      ET(A) receptor antagonist, induced a significant leftward shift of the ET-1
      concentration-response curve (CRC). This leftward shift was abolished after
      epithelium removal. 3. L-NAME (3 x 10(-3) M), an inhibitor of nitric oxide (NO)
      synthase, induced a significant leftward shift of the ET-1 CRC, and abolished the
      potentiation by BQ-123 (10(-8) M) of ET-1-induced contraction. 4. In intact
      preparations, the ET(B) receptor antagonist BQ-788 induced only at 10(-5) M a
      slight rightward shift of the ET-1 CRC. In contrast, in epithelium-denuded
      bronchi or in intact preparations in the presence of L-NAME, BQ-788 displayed a
      non-competitive antagonism toward ET-1-induced contraction. 5. IRL 1620, a
      selective ET(B) receptor agonist, induced a contraction of the isolated bronchus
      (-logEC50=7.94+/-0.11, n= 19). This effect was not modified by epithelium removal
      or by BQ-123. BQ-788 exerted a competitive antagonism against IRL 1620 which was
      similar in the presence or absence of epithelium. 6. These results show that ET-1
      exerts two opposite effects on the human airway smooth muscle. One is contractile
      via ETB-receptor activation, the other is inhibitory and responsible of NO
      release which counteracts via ETA-receptor activation the contraction.

PMID- 10077249
TI  - Aging does not alter phosphoinositide hydrolysis in the rat cochlear lateral
      wall.
AB  - We have previously reported that the inositol 1,4,5-trisphosphate (InsP3) second
      messenger system is coupled to purinergic P2y receptors in the cochlear sensory
      epithelium and lateral wall. The tissues of the cochlear lateral wall (stria
      vascularis and spiral ligament) are responsible for maintaining the ionic
      composition of the cochlear endolymph. Both the endolymphatic potential and
      signal transduction processes are well known to be affected by aging.
      Furthermore, intracellular inositol concentrations decrease with age in the
      cochlear sensory epithelia. The present study compared the purinergic receptor
      mediated release of inositol phosphates (InsPs) in the cochlear lateral wall of
      young (3 month-old) and aged (24 month-old) Fischer-344 rats. No differences were
      found in the incorporation of mnyo-[3H]inositol into phosphoinositide lipids.
      Likewise, the purinergic receptor-mediated release of InsPs remained unchanged.
      This suggests that the InsPs second messenger system in the cochlear lateral
      wall, in contrast to the sensory epithelium, may not be affected by aging.

PMID- 10077250
TI  - Trans-mucosal inert gas exchange constants for the monkey middle ear.
AB  - OBJECTIVE: The purpose of the study was to estimate the exchange constants for
      Argon and N2 across the middle ear mucosa of monkeys for use in mathematical
      models of middle ear pressure regulation. METHODS: In five anesthetized monkeys,
      the tympanic membrane was perforated and, with the animal breathing room air, a
      13-ml probe attached to an Argon gas source and to a pressure transducer was
      introduced into the ear canal and sealed. The probe and middle ear volume was
      washed with Argon and then closed to the gas source. Gas samples were withdrawn
      from the probe at 15-min intervals for composition analysis using an online mass
      spectrometer. Probe partial pressures of Argon and N2 were regressed on time and
      the slopes of those functions were divided by the respective average partial
      pressure gradient for the interval to estimate the exchange constants. RESULTS:
      The average trans-mucosal exchange constants for Argon and N2 were 0.0007 +/-
      0.0001 and 0.0003 +/- 0.0001/min, respectively. The average ratio of the two
      constants was 2.60 +/- 0.36 which is not different from the value of 2.3
      predicted for perfusion limited gas exchange. CONCLUSION: These results confirm a
      very slow, perfusion limited trans-mucosal exchange of N2 and other inert gases
      across the middle ear mucosa. They infer that the required frequency of
      Eustachian tube openings to prevent the development of middle ear effusion is low
      and on the order of one/day.

PMID- 10077251
TI  - Less radical drilling in surgery for exostoses of the external auditory canal.
AB  - OBJECTIVE: To estimate the anatomical and functional long-term result of surgery
      for ear canal exostosis. METHODS: Case rapport review with extraction of data
      concerning pre- and postoperative anatomical conditions, symptoms and audiology
      and a clinical and audiological re-evaluation. In the 20-year-period from 1
      January 1976 to 1 January 1996, 26 patients were operated on primarily for ear
      canal exostosis. 19 patients with in total 24 ears were re-evaluated. Control
      period 7.2 years. Pre-operatively were found occluding ear-canal exostosis in all
      patients as well as hearing loss, otitis externa and pain. RESULTS: At the re
      evaluation all patient were completely free of their symptoms. 19 out of 24 ears
      still had some remnants of exostosis, but the ear canal was covered with
      completely normal skin and had normal migration properties. No signs of re-growth
      were found in this material. Postoperatively one patient had a sensorineural
      hearing loss of 85 dB at 6 kHz, one had a dehiscence of the temporomandibular
      joint and one patient had an anterior ear drum perforation. CONCLUSION: To avoid
      the complications a less radical drilling of exostoses is proposed, in particular
      along the superior wall and near the short process of the malleus handle and
      along the anterior tympanomeatal angle. Removal of the bone from the posterior,
      inferior and anterior walls with preservation of the canal skin, creates enough
      lumen providing permanent cure.

PMID- 10077252
TI  - Variable-speech-rate audiometry for hearing aid evaluation.
AB  - A new hearing aid evaluation method using variable-speech-rate audiometry (VSRA)
      was developed. VSRA was newly created based on the Japanese speech audiometry
      authorized by the Japan Audiological Society. The ordinary speech audiometry can
      not reveal a temporal factor in word discrimination ability of the hearing
      impaired. Since, with VSRA, we can compare several performance-intensity curves
      obtained from different speech-rate speech audiometries, the impact on the
      auditory system of each patient by the fast or slow speech rate could be easily
      determined. Taking the temporal factor of the auditory systems into consideration
      by using VSRA, hearing aid evaluation was performed for a master hearing aid with
      three types of signal processing and fitting for 36 hearing impaired subjects.
      Then hearing aid evaluation was performed using VSRA for a newly developed
      portable multi-function digital hearing aid with two types of signal processing
      and analog hearing aids which had been used by hearing-impaired patients. As a
      result, VSRA was useful for hearing aid evaluation, in particular, for cases when
      ordinary normal speech rate audiometry does not provide a significant difference
      in word discrimination scores. In addition, using VSRA revealed that amplitude
      compression is more effective for improvement of word discrimination than linear
      amplification.

PMID- 10077253
TI  - The leaking labyrinthine lesion resulting from direct force through the auditory
      canal: report of five cases.
AB  - The leaking labyrinthine lesion is treated by conservative methods or surgical
      procedures. With respect to the stapes, the surgical treatment is controversial.
      Five cases of middle ear injuries accompanying oval window rupture are reported
      herein. In each case, direct force through the auditory canal damaged not only
      the ossicular chain but also the oval window. Initial symptoms were sudden
      hearing loss with significant conductive disturbance and various degrees of
      unsteadiness. Spontaneous horizontal nystagmus directed toward the uninvolved ear
      was observed in each case. Tympanic cavities were promptly explored under general
      anesthesia and oval window injuries were confirmed. In each case, the damaged
      stapes was temporally removed from the oval window. Perilymphatic leakage was
      recognized in each case. Two patients had subluxation of the stapes with a
      paucity leakage. Three had complete luxation of the stapes with a relatively huge
      oval window fistula. Disrupted oval windows were repaired with temporalis muscle
      fascial grafts that were inserted under the middle ear mucosae surrounding the
      oval windows. The stapes were replaced in the repaired oval windows, and the
      ossicular chains were reconstructed without artificial grafts. Vestibular
      dysfunctions disappeared within 7 days, and satisfactory audiologic results were
      obtained in each case.

PMID- 10077254
TI  - Bilateral middle ear squamous cell carcinoma and clinical review of an additional
      5 cases of middle ear carcinomas.
AB  - We reported a retrospective review of the clinical records for a 64 year old male
      patient with bilateral middle ear squamous cell carcinoma (MESCC), and for the
      five other patients with MESCC treated at our institution during the last 20
      years. The patient with bilateral MESCC has survived and remained tumor free for
      more than 1.5 years after extended radical resection of the secondary tumor
      combined with intra-arterial and systemic chemotherapy, radiotherapy and
      immunotherapy. Four patients with unilateral MESCC were treated with
      multidisciplinary treatment (induction chemotherapy, surgery and radiotherapy),
      and the remaining patient was treated with radiotherapy and mastoidectomy. Five
      of the six patients are alive with no evidence of disease. The patient treated
      with radiotherapy and radical mastoidectomy died of local recurrence 3 years
      after diagnosis. We suggest that MESCC should be considered when refractory
      granulation, long-standing otorrhea, otalgia and facial paralysis are observed.
      Multidisciplinary treatment, including intra-arterial chemotherapy and en bloc
      resection of the temporal tumor is useful for the treatment of MESCC and will
      improve the prognosis of patients with this disease.

PMID- 10077255
TI  - Anatomic variations of the paranasal sinuses: CT examination for endoscopic sinus
      surgery.
AB  - Chronic rhinosinusitis endoscopic surgery requires an accurate evaluation of
      diseases and paranasal sinus anatomic variations. This study aims to show the
      main anatomical variations in the ostiomeatal complex and paranasal sinuses which
      are usually depicted by computed tomography (CT). CT scans obtained 2 mm
      thickness in axial and coronal plane from a series of 200 patients with chronic
      sinusitis were examined to determine the prevalence of anatomic variants.
      Anatomical variations determined were supraorbital recess in 6%, concha bullosa
      in 30%, sphenomaxillary plate in 17%, infra-orbital ethmoid cells (Haller's
      cells) in 6%, spheno-ethmoid cells (Onodi's cells) in 12%, pneumatization of the
      anterior clinoid process in 6%, carotid artery bulging into the sphenoid sinus in
      8%, pneumatization of the uncinate process in 2%, paradoxical curvature of the
      middle turbinate in 3% and septal deviation in 36%. Level difference between the
      ethmoid roof and nasal vault was an average of 8 mm in right side and 9.5 mm in
      left side. Awareness of these different variations will help the rhinologic
      surgeon in his orientation during endoscopic surgical procedures.

PMID- 10077256
TI  - Topical treatment of nasal polyps with a beclomethasone dipropionate powder
      preparation.
AB  - The clinical efficacy of a topical preparation consisting of beclomethasone
      dipropionate (BDP) powder and a mucous membrane adhesive agent
      (hydroxypropylcellulose, HPC) for nasal polyps was examined. For 1 week, in 31
      patients with bilateral nasal polyposis, the clinical efficacy of the topical BDP
      HPC powder treatment was examined. The effect of this treatment on the histology
      of the nasal polyps was also investigated. The controls were six patients with
      bilateral nasal polyposis, who underwent identical surgery without prior use of
      the topical steroid therapy. Polyp shrinkage and improvement of some nasal
      symptoms (rhinorrhea, ease of noseblowing, and nasal blockage) were observed with
      the topical treatment. Significant clinical improvement (P < 0.05) was seen in
      the group treated with topical BDP HPC powder compared with the untreated control
      group. Histological examination of the excised nasal polyps in both groups
      demonstrated no clear differences attributable to BDP HPC powder. The topical
      treatment of nasal polyps with BDP HPC powder is a useful conservative therapy.

PMID- 10077257
TI  - Malignant tumours of the nasal cavity and the paranasal sinuses in a Melanesian
      population.
AB  - Malignant tumours of the nasal cavity and paranasal sinuses are usually
      associated with poor prognosis. From 1986 to 1995, 50 such tumours were managed
      in Papua New Guinea. Twenty-nine of these arose in the maxillary sinus, 15 in the
      nasal cavity, four in the ethmoid sinus and two in the frontal sinus. Males were
      more frequently affected than females. No specific carcinogenic factor was
      apparent in these patients who were uniformly distributed all over the country.
      Advanced local disease with multiple symptoms and signs was common during
      presentation. Systemic and neck node metastases were infrequent.
      Histopathologically, squamous cell carcinoma was the commonest type of tumour.
      Satisfactory results were obtained by combination therapy consisting of surgery,
      irradiation, and systemic chemotherapeutics agents. Better health consciousness
      and health care delivery system are essential for early diagnosis, regular
      posttreatment follow-up and improved survival of these patients.

PMID- 10077258
TI  - Effect of chewing gum on recovery after tonsillectomy.
AB  - OBJECTIVE: Patients are traditionally advised to eat early and frequently in the
      initial post-tonsillectomy period to reduce the severity of pain and to
      facilitate early resumption to a normal diet. We investigated the action of
      mastication and therefore the promotion of saliva formation and deglutition on
      the post-operative recovery of tonsillectomy patients. METHODS: We present a
      prospective randomised controlled trial set up to observe the effects of chewing
      gum on these patients. One hundred and two patients undergoing routine
      tonsillectomy for recurrent tonsillitis were randomised into cases (those given
      chewing-gum) and control groups (those not given chewing-gum). Eighty-four
      patients were reviewed on the seventh post-operative day. We measured the time
      taken in days for the subjects to resume to their normal diet after surgery and
      measured pain on a daily basis. RESULTS: Our study demonstrated that chewing gum
      in the early post-operative period significantly delayed resumption of normal
      diet (Chi-squared test with Yates' correction, chi2= 4.6, P = 0.032). Chewing gum
      also increased the average amount of pain experienced by the cases over the
      controls and this became statistically significant on day 7 (mean difference =
      14.8, t-test with two tailed probability, P = 0.041). CONCLUSION: We conclude
      that chewing gum should not be routinely advised in the early period following
      tonsillectomy.

PMID- 10077259
TI  - Speech rehabilitation after laryngectomy with the amatsu tracheoesophageal shunt.
AB  - The Amatsu vocal rehabilitation technique is a tracheoesophageal shunt using a
      posterior tracheal flap associated with a sphincter made of esophageal muscular
      wall. Since march 1991 the procedure was done in 33 men and 2 women. ages ranging
      from 30 to 78 years. Previous radiotherapy, hypopharynx lesions, need for
      postoperative radiotherapy or use of myocutaneous flap were not considered
      contraindications. Vocalization was achieved in 76% of our patients and the
      quality was considered superior than that obtained by the esophageal voice. In
      only one case the shunt had to be closed surgically because of aspiration. In
      conclusion, the Amatsu tracheoesophageal shunt is an inexpensive technique that
      obtain a good quality of vocal rehabilitation in a high percentage of patients,
      it has few complications and it should be considered for all candidates to a
      laryngectomy, mainly for those with a good prognosis and a desire to return to
      their social environment.

PMID- 10077260
TI  - Fibrous dysplasia of the temporal bone and maxillofacial region associated with
      cholesteatoma of the middle ear.
AB  - Fibrous dysplasia of the temporal bone is a rare disease which may lead to
      progressive stenosis of the external auditory canal and the development of
      cholesteatoma. We present a case in which minimal symptoms were present despite a
      massive temporal bone fibrous dysplasia. Cholesteatoma resulted most probably
      secondary to external auditory canal stenosis. Retroauricular fistula developed
      as a result of destructive effect of cholesteatoma, that influenced previous
      diagnosis and treatment of this clinically silent disease.

PMID- 10077261
TI  - Primitive neuroectodermal tumor in sinonasal region.
AB  - An elderly woman having a nasal tumor diagnosed as alveolar rhabdomyosarcoma was
      referred to our hospital. Histological reexamination of the patient revealed that
      the tumor was composed of lobules of compactly arranged small round atypical
      cells. The atypical cells contained large oval to round vesicular nuclei, and
      scanty cytoplasm showing PAS positive glycogen material. The tumor cells were
      immunohistochemically positive for NSE, S-100 protein and vimentin, but showed
      negative reaction for myoglobin, desmin, EMA, keratin, LCA, chromogranin and
      MIC2. Ultrastructurally, the tumor cells contained a few cluster of glycogen
      particles and less organellae and filaments, and there were no cytoplasmic
      processes, neurosecretory granules or neurofilaments. Pathological findings
      suggested primitive neuroectodermal tumor resembling extraskeletal Ewing's
      sarcoma, but negative reaction for MIC2 immunohistochemically could not ascertain
      the diagnosis. Location of the tumor and age of the patient of the present case
      were unusual.

PMID- 10077262
TI  - Synovial sarcoma in the parapharyngeal space: case report and review of the
      literature.
AB  - We encountered a rare case of synovial sarcoma in the parapharynx of a 47-year
      old Japanese man. This patient presented with an enlarging tumor in the right
      side of his neck that had grown progressively over a 4-week period. Radiological
      examinations revealed that the tumor arose from the parapharyngeal space. The
      tumor could not be completely removed at surgery. Metastasis to the lumbar
      vertebra was detected postoperatively. The patient underwent three courses of
      chemotherapy and the delivery of palliative radiation to the lumbar vertebra
      without success. The patient died of lung metastasis 7 months after surgery.

PMID- 10077263
TI  - A case of laryngeal neurinoma with neurofibromatosis 2.
AB  - We present a case of a laryngeal neurinoma in a patient with neurofibromatosis 2.
      A 39-year-old man presented to our hospital with multiple complaints including
      progressive bilateral hearing loss, dizziness, dyspnea, dysphagia, and a 9-year
      history of right lower leg weakness. Magnetic resonance imaging demonstrated
      multiple lesions including bilateral cerebellopontine angle tumors, a foremen
      magnum tumor, multiple tumors of the spinal cord, a laryngeal tumor, and several
      retrocervical tumors. Fiberoptic laryngoscopy revealed a large submucosal
      supraglottic tumor. The laryngeal tumor was visualized through microlaryngoscopy
      and excised with a KTP laser directed through a quartz fiber.

PMID- 10077264
TI  - Sudden recurrent laryngeal nerve paralysis due to apoplexy of parathyroid
      adenoma.
AB  - Neoplastic lesions of the parathyroid are rare, and most of these are adenomas.
      Even rarer is a secondary involvement of the recurrent laryngeal nerve. A case is
      presented of sudden onset hoarseness in a 64-year-old man caused by acute vocal
      cord paralysis due to bleeding within an adenoma of the lower right parathyroid
      gland. Acute onset of vocal cord paralysis is rarely associated with benign
      processes; the current case is only the second report associated with parathyroid
      adenoma.

PMID- 10077265
TI  - Molecular dynamics study of kaliotoxin in water.
AB  - Kaliotoxin (KTX), a potassium channel blocker found in the venom of the scorpion
      Androctonous Mauretanicus is a 38 residue polypeptide with a well defined
      structure consisting of a alpha-helix and a three strand antiparallel beta-sheet
      interconnected by three disulfide bonds. Although the 3D structure has been
      determined by NMR, there is a number of features, mainly concerning the
      conformation and flexibility of the side chains, but also the long range order in
      the peptide and its fluctuations, that may have escaped the experimental study.
      These questions are now being addressed using molecular dynamics (MD)
      simulations. Accordingly, the present work reports the analysis of a 430 ps
      molecular dynamics trajectory of the polypeptide soaked with 4700 TIP3 water
      molecules inside a 56 A box. MD calculations were performed with periodic
      boundary conditions. Analysis of the conformational space sampled by each of the
      residues along the trajectory, suggests a special behavior of Pro17 and Lys19
      both located on the helix. Furthermore, analysis of the relative movements of the
      secondary structure elements indicates that the alpha-helix and beta-sheets
      fluctuate in a correlated motion, preserving the tertiary structure of the
      polypeptide along the trajectory. Finally, analysis of the charge distribution
      was also examined. The direction of the dipole moment, computed from the center
      of masses appears to be an interesting feature of the structure probably related
      to the biological function of the molecule.

PMID- 10077266
TI  - Structural and functional heterogeneity of the amino-terminal receptor-binding
      domain of human interferon-alpha 2.
AB  - Structural immunoanalysis of human interferon (IFN)-alpha 2c revealed antigenic
      and functional heterogeneity in its N-terminal receptor-binding domain (loop AB).
      Monoclonal antibodies (mAbs) mapped to the region 30-53 of IFN-alpha 2 defined
      three partially overlapping antigenic sites designated here as 'a', 'b' and 'c'.
      For the high-affinity binding of IFN-alpha 2c to the cellular receptor, site b
      located in segment 34-41 and site c (residues 43-53) appeared to be most
      important. Only the part of site a (amino acids 30-33) seemed to be involved in
      the interaction with receptor. The segment of residues 30-46 forms a relatively
      straight structure on the protein surface, according to the three-dimensional
      model of human IFN-alpha 2.

PMID- 10077267
TI  - Metachromatic activity of beta-cyclodextrin sulfates as heparin mimics.
AB  - Heparin is a versatile biologically active substance which has been reported to
      have an inhibitory effect on angiogenesis if administered together with
      hydrocortisone. Since very little is known about the mechanism of this activity,
      beta-cyclodextrin sulfates were prepared to mimic heparin. The sulfate groups
      were introduced into beta-cyclodextrin regioselectively using protecting groups.
      The obtained polyanions were tested for their complex binding properties by
      mixing them with cationic dyes and measuring the metachromatic response which
      proved to be a very useful tool to evaluate the biological activity of these
      compounds. The results reveal that the activity depends largely upon the charge
      density at the surface of the beta-cyclodextrin sulfates: a large number of
      sulfate groups or anionic groups relatively close to each other display high
      activity, whereas molecules with fewer sulfate groups or with them more distant
      from each other exhibit smaller activities.

PMID- 10077268
TI  - Prediction of a conserved, neutralizing epitope in ribosome-inactivating
      proteins.
AB  - The secondary structures, side-chain solvent accessibilities, and superpositioned
      crystal structures of the A-chain of ricin and four other plant rRNA N
      glycosidases (ribosome-inactivating proteins, RIPs) were examined. Previously, a
      26-residue fragment from the A-chain of ricin was determined to bind to a
      neutralizing monoclonal antibody. The region in the native ricin A-chain, to
      which this peptide corresponds, is solvent-exposed and contains a negatively
      charged residue that has been hypothesized to participate in the toxin's
      function, namely, rRNA binding and/or enzymatic activity. This region appears to
      be conserved in all of the structurally defined plant RIPs examined. Moreover,
      other plant RIPs, whose tertiary structures are, as yet, unknown, were predicted
      to have an analogous, solvent-exposed region containing a conserved, negatively
      charged residue. By analogy, these conserved structural and functional features
      lead to the suggestion that this exposed region represents a logical starting
      point for experiments designed to locate neutralizing epitopes in these RIPs. In
      contrast, the tertiary structure of the analogous region in a bacteria-derived
      RIP (Shiga toxin) is a less solvent-exposed, truncated loop and is a structure
      that is not as likely to be a neutralizing epitope. Because most of the amino
      acid residues are not conserved within this exposed region, these RIPs are
      predicted to be antigenically distinct.

PMID- 10077269
TI  - Phosphofructokinase-1 from Saccharomyces cerevisiae: analysis of molecular
      structure and function by electron microscopy and self-catalysed affinity
      labelling.
AB  - Conventional and cryoelectron microscopy portray native octameric yeast
      phosphofructokinase-1 (PFK) as consisting of two identical heterotetrameric
      tetrahedron-like moieties being rotated relative to each other. Immunoelectron
      microscopy employing subunit-specific IgG identifies alpha-type subunits in the
      contact zone of the two tetrahedrons, while beta-chains are recognized
      exclusively at the tips of the octamer. The chemical reaction of
      phosphofructokinase with analogues of fructose 6-phosphate followed by
      autocatalytic phosphoryl transfer from [gamma-32P]-ATP results in a specific
      labelling of the alpha-subunit. AMP and fructose 2,6-bisphosphate affect
      labelling by stimulating the binding of substrate analogue; AMP additionally
      promotes phosphoryl transfer. No stimulation of labelling is observed with
      proteolytically modified tetrameric 12-S phosphofructokinase.

PMID- 10077270
TI  - Quantitative analysis for the cellulose I alpha crystalline phase in developing
      wood cell walls.
AB  - FT-IR and X-ray analyses were employed to determine the relative ratio of
      cellulose Ialpha and Ibeta crystalline phases present in each developmental stage
      of coniferous tracheid cell wall formation. The IR spectra showed that initially
      the Ialpha phase occupies 50% of the crystalline regions in the primary cell wall
      cellulose and this value drops to 20% after ceasing of the cell enlarging growth
      for the formation of the secondary wall cellulose (the remaining regions are
      composed of the Ibeta phase). Although it is reasonable that the content for
      Ibeta, which is stress-reduced crystalline form, was higher in the secondary wall
      formation (Kataoka Y, and Kondo T. Macromolecules 1996;29:6356 6358) it is more
      interesting that during the crystallization of stress-induced Ialpha cellulose
      for the primary wall the stress-reduced Ibeta, is also possible to be
      crystallized in an alternative way. This means that throughout the period the
      Ialpha-causing stress may not be necessarily kept loaded. In light of our
      previously reported hypothesis (Kataoka Y. and Kondo T. Macromolecules
      1998;31:760-764) for the formation of Ialpha phase due to cellular growing
      stresses in the primary wall cellulose, such an alternating on-off stress effect
      to account for the occurrence of both Ialpha and Ibeta phases might be related to
      a biological growth system in coniferous wood cells.

PMID- 10077271
TI  - A study of strontium binding to albumins, by a chromatographic method involving
      atomic emission spectrometric detection.
AB  - A chromatographic method involving ICP-AES (inductively coupled plasma atomic
      emission spectrometry) detection has been successfully applied for the study of
      strontium-protein complexes. The chromatographic step involves the use of gel
      filtration-a large-zone Hummel and Dreyer method-which allows to dissociate the
      bound metallic ions and the free ones. This step is followed by an ICP-AES
      analysis of fractions collected throughout the chromatographic experiment: the
      concentration of ionic metallic species in solution can therefore be calculated.
      Two proteins have been tested: bovine serum albumin, which showed only weak
      interactions with Sr2+ ions, and bovine alpha-lactalbumin: this protein, well
      known for its calcium binding capacity, proved to interact strongly with
      strontium. The influence of various parameters on the formation of strontium
      lactalbumin complexes were determined, namely temperature, pH. Competition
      experiments between Sr2+ ions and, respectively Na+ and Ca2+ ions were also
      performed, by varying ionic strength of the medium, and by using both apo and
      native forms of bovine alpha-lactalbumin.

PMID- 10077272
TI  - Study of molybdate ion sorption on chitosan gel beads by different spectrometric
      analyses.
AB  - Molybdate ion uptake both by raw chitosan and by glutaraldehyde cross-linked
      chitosan beads was investigated. This study focused on the identification of
      sorption mechanisms by means of several analytical procedures such as infra-red
      and reflectance spectrophotometries and CP-MAS 13C NMR analyses. Although the
      amine functions of glucosamine residues remain the major sites of interaction
      with the metal species, other functional groups can also be involved. It is
      certainly the case with carbonyl functions provided by the glutaraldehyde
      structure in cross-linked sorbents. Due to the large size of the polynuclear
      hydrolysed molybdate species, the sorption may involve several monomer units,
      resulting in additional linkages between the polymer chains. This behaviour can
      be confirmed by the chemical shifts of the carbon atoms observed by CP-MAS 13C
      NMR on raw chitosan beads, showing that the carbon atoms supporting the amino
      sites are not the only atoms affected by molybdate ion sorption. Moreover, cross
      linking promotes a partial reduction of molybdenum species in the presence of
      some unreacted aldehyde groups.

PMID- 10077273
TI  - Structure of extracellular polysaccharide produced by lignin-degrading fungus
      Phlebia radiata in liquid culture.
AB  - The extracellular material (EM) produced by the white rot fungus Phlebia radiata
      cultured in an N-limited liquid medium was studied. Carbohydrate analysis showed
      maximum concentration of glucose as the major monosaccharide component of EM was
      found on postinoculation day 9. Beyond day 9 of cultivation the proportion of
      glucose decreased suggesting that the glucan component of EM had been further
      metabolized. The analysis of EM at day 9 revealed the presence of the following
      monosaccharides (in relative %): glucose (62); galactose (16); mannose (13);
      xylose (4); and fucose (5). The carbohydrate analysis together with the presence
      of protein in EM corresponds to a mixture of glucan and glycoprotein.
      Purification by trypsin treatment yielded an enriched glucose-containing
      extracellular polysaccharide (EPS). Methylation analysis identified EPS as (1-3)
      beta-D-glucan highly branched at C-6. The structure of the glucan was confirmed
      by 13C-NMR spectroscopy. The results suggest that P. radiata's EPS is entangled
      with a glycoprotein in a complex that makes the extracellular sheath surrounding
      the hyphae.

PMID- 10077274
TI  - Size and folding in globular proteins.
AB  - We have modeled protein folding by packing a unified length of regular structural
      elements (alpha-helices and beta-sheets) into a 'cube'. In a globular protein
      with m alpha-helices and n beta-strands, this unified length is expressed in
      units of heptapeptides in alpha-helices, and in units of tripeptides in beta
      strands. Calculations using published data show that a 4-helix bundle (m = 4, n =
      0) has at least 2 x 2 x 2 helical heptapeptides; the 16-strand beta-barrel of
      porin (m = 0, n = 16) is at most 4 x 4 x 4 tripeptides in beta-strands. Compact,
      recurring protein modules with mixed helices and beta-strands are the ones that
      actually acquire a geometrically quasi-spherical, or cubic, shape.

PMID- 10077275
TI  - Kinetic approach to the interaction of sodium n-dodecyl sulphate with heme
      enzymes.
AB  - The kinetics of interaction of sodium n-dodecyl sulphate (SDS) with catalase has
      been studied by absorbance and fluorescence changes. The results have been
      compared with circular dichroism spectra and activity measurements. The tertiary
      structure of catalase is modified by SDS in the monomeric and micellar form. The
      secondary structure of catalase is altered only in the presence of SDS micelles.
      On the other hand, neither spectroscopic properties nor activity of horseradish
      peroxidase change in the presence of SDS below micellar concentration. In the
      presence of SDS micelles, however, changes of secondary and tertiary structure of
      this protein are detected. The reason for relatively high stability of
      horseradish peroxidase in the presence of SDS is discussed.

PMID- 10077276
TI  - Gender, sexuality, and the prevention of sexually transmissible diseases: a
      Brazilian study of clinical practice.
AB  - Epidemiological tendencies in the spread of HIV/AIDS in Brazil demonstrate the
      increasing importance of heterosexual transmission to women who are not included
      in those traditional categories of 'risk' which have so far guided research and
      attempts at prevention. While more attention is now being given to other STDs as
      part of HIV prevention, this same view of 'risk' prevails, as does a tendency to
      rely on strictly quantitative indicators and conceptions which treat health care
      workers' beliefs and attitudes as individual phenomena. This study, an
      examination of clinical practices of STD management in gynecological and
      antenatal programs in public health posts in Rio de Janeiro, reveals the mutually
      reinforcing relationship between gender norms in sexuality and gynecological
      clinical practices, which results in the reproduction of both gender hierarchy
      and vulnerability to infection by all STDs.

PMID- 10077277
TI  - The social impact of HIV testing: a comparative analysis of Britain and Sweden.
AB  - The role of HIV testing in the primary prevention of HIV is as yet unclear.
      Whereas most outcome evaluations have tended to focus on the impact of HIV
      testing and counselling on individuals' risk behaviours, this paper argues for a
      fresh perspective on HIV testing which takes into account its social impact. To
      illustrate the importance of the social impact of HIV testing, the paper compares
      HIV testing policies in the context of HIV prevention in Britain and in Sweden.
      It shows how contrasting representations of HIV testing and different practices
      around testing have had different social, economic and public health consequences
      in the two countries. The paper concludes with a recommendation that policy
      makers take fuller account of the social dimension of HIV testing in the future
      development of HIV testing policies.

PMID- 10077278
TI  - Birth intervals, breastfeeding and determinants of childhood mortality in Malawi.
AB  - Childhood mortality in Malawi is analyzed by employing proportional hazards
      models. The analysis uses highly reliable data collected from the 1992
      Demographic and Health Survey (DHS) of Malawi. The results show that the
      substantial birth interval and maternal age effects are largely limited to the
      infant period. The influence of social and economic variables on the mortality
      risk and on the relationship between biodemographic variables and mortality risk
      is much enhanced with increasing age of the child. It has also been found that
      consideration of breastfeeding status of the child does not significantly alter
      interpretation of effects of preceding birth interval length on mortality risk,
      but does partially diminish the succeeding birth interval effect. The results are
      discussed and then summarized in the context of policy implications for Malawi.
      The paper addresses a very important issue in Malawi and it adds valuable
      insights to the base of knowledge in childhood mortality in sub-Sahara Africa.

PMID- 10077279
TI  - Postpartum health in a Dhaka slum.
AB  - This study examines the health, nutritional status, and health care seeking
      behaviour of a community based sample of 122 postpartum women from an urban slum
      in Dhaka, Bangladesh. It describes a physically impoverished environment in which
      malnutrition is serious, and non-trivial morbid episodes as a consequence of
      childbirth are very common. Malnutrition was found to be widespread: about one
      quarter of the study mothers were short in stature, measuring 145cm or less in
      height; over two-thirds of the women weighed <45 kg; and a similar proportion had
      a BMI of <20. Based on mid-upper arm circumference, an overwhelming majority
      (96%) suffered from some degree of malnutrition. During the first 6 weeks
      postpartum over three-quarters of the women reported a non-trivial illness. The
      frequency of reported illnesses was significantly associated with both increasing
      age and parity. Despite severe poverty, most of the women reporting illnesses
      (71%) received some form of health care from a wide range of western and
      traditional health care providers, with Traditional Birth Attendants (TBAs) and
      unqualified western care providers being the most frequently utilised. This study
      highlights the plight of these women in a precarious environment and shows how
      their health is compromised by cultural and political constraints. We conclude
      that while the burden of postpartum morbidity is very high, the incorporation of
      traditional practitioners and unqualified western care providers into maternal
      health training programs, together with efforts to empower women, could be
      effective in improving the health status of mothers in this marginalised and
      fragmented community. To achieve this outcome, a clearly articulated and
      integrated approach to development in slum communities is required.

PMID- 10077280
TI  - Accidents to preschool children: comparing family and neighbourhood risk factors.
AB  - Accidental injury in young children is more common among poorer families and in
      deprived areas but little is known about how these factors interact. This paper
      describes a study to measure the contribution of individual family factors and
      area characteristics in determining risk of accidental injury among preschool
      children. We conducted a population based study of preschool accident and
      emergency attendances over two years in and around the city of Norwich, UK.
      Information on individual families was extracted from the district child health
      information system while "social areas" were constructed from adjacent census
      enumeration districts with homogeneous social and demographic characteristics.
      Statistical analysis was by multilevel modelling. Accidental injury rates were
      much higher in deprived urban neighbourhoods than in affluent areas but the
      multilevel analysis showed that, for all accidents, much of the variation in
      rates was accounted for by factors at the individual level i.e. male sex, young
      maternal age, number of elder siblings and distance from hospital, with a
      smaller, but independent, influence of living in a deprived neighbourhood. The
      model for more severe injuries was similar except single parenthood was now
      significant at the level of individuals and the effect of area deprivation was
      stronger. We conclude that preschool accidental injuries are influenced by
      factors operating at both the level of individual families and between areas.
      This evidence suggests that both social policy changes to improve child care
      among unsupported young families and targeting accident prevention measures at a
      local level towards deprived neighbourhoods would reduce accidents.

PMID- 10077281
TI  - Costs of formal care for frail older people in England: the resource implications
      study of the MRC cognitive function and ageing study (RIS MRC CFAS).
AB  - The aim of this paper is to quantify service use and costs of supporting frail
      older people at home in the community, using data collected in a longitudinal
      multicentre stratified randomised study for 1055 mentally frail, physically
      frail, and mentally and physically frail subjects. Average costs per person per
      week were found to total 64.45 Pounds Sterling, with a small number of services
      accounting for a large proportion of the total costs. The level of services
      offered by the nonstatutory voluntary and private sectors was found to be small.
      To highlight issues for policy makers, the extent of cost variations between a
      number of different subgroups were calculated. These bivariate analyses revealed
      substantial variation in costs, especially according to household structure, type
      of frailty, whether admission to continuing care accommodation occurred and
      survival. Multiple regression analysis demonstrated that 26% of the variation in
      log average weekly costs could be explained by a number of socio-demographic and
      health status variables. A particularly close relationship was observed between
      costs and whether admission to continuing care accommodation occurred,
      highlighting a need for policy-makers to examine the nature and scale of
      provision of alternative community based care packages. The results demonstrate
      that descriptive cost data such as those presented can provide information useful
      to the planning process, enabling more informed choices to be made over the
      provision of services for particular groups of people.

PMID- 10077282
TI  - The medical profession and alternative medicine in The Netherlands: its history
      and recent developments.
AB  - At the end of 1993, the Dutch parliament passed the Individual Health Care
      Professions Bill which replaced existing legislation. The new Act brings to an
      end the monopoly of the Dutch medical profession. The former prohibition on
      alternative practitioners to practice medicine was abolished. This article
      addresses the question of whether the Act affects the position of medical
      dominance in Dutch health care. It will be argued that the new Act preserves the
      present position of medical dominance to a large extent. Although alternative
      therapies have gained greater social recognition, there is little indication that
      the cultural and social authority of medicine is yet being challenged in the
      Netherlands. However, it could be argued that the Dutch health care system is
      moving in a more pluralistic direction.

PMID- 10077283
TI  - Procedures and the professional: the case of the British NHS.
AB  - The introduction of procedures to guide medical practice is a growing phenomenon
      in the British National Health Service. It is thought to be a useful way of
      managing risk, standardising practice and ensuring that research evidence is
      incorporated into patient care. However, the mere development and introduction of
      procedures does not ensure that they are actually followed. In the research
      reported here focus group methodology was used to investigate the perceptions and
      opinions of doctors, nurses, midwives and health service managers. Twenty-four
      focus groups were convened across three hospitals, with discussion focusing on
      the purpose, development and implementation of clinical protocols. The effect of
      proceduralisation on professional autonomy and on the working relationships among
      professional groups also emerged as important themes. The paper concludes that
      successful implementation of protocols or guidelines in the NHS depends on
      achieving the right balance between standardising practice and allowing
      professionals to use clinical judgement. Successful implementation of clinical
      guidelines also requires that the culture of the health service and the beliefs,
      attitudes and norms of its employees are taken into account.

PMID- 10077284
TI  - Complaints against nurses: a reflection of 'the new managerialism' and
      consumerism in health care?
AB  - This paper discusses the effects of restructuring on nursing as a profession
      through an examination of the issue of complaints in Ontario. It argues that new
      managerialist techniques and associated changes in the nature of work are
      reducing the autonomy of nurses and making it difficult for them to meet the
      standards of their profession. Simultaneously, the Ontario government has
      increased the power of the public in the disciplinary process and the College of
      Nurses of Ontario is encouraging patients to register their complaints. The
      growth of consumerism in health care, coupled with the disciplinary process,
      individualizes complaints and deemphasizes their relationship to restructuring.
      Moreover, in response to the increasing number of complaints - complaints which
      more often come from the public - nursing organizations have encouraged the
      legalization of the disciplinary process, thus fostering the individualization of
      the issues.

PMID- 10077285
TI  - Smoking-attributable medical care costs in the USA.
AB  - Medical care costs attributable to cigarette smoking are estimated using an
      econometric model of annual individual expenditures for four types of medical
      services: ambulatory, hospital, prescription drug, and other (which includes home
      health and durable medical equipment and excludes dental and mental health). The
      model follows the two-part specification of Duan et al. (1983). Estimation is
      carried out using the 1987 National Medical Expenditure Survey. Fitted values are
      used to calculate smoking-attributable fractions (SAFs) of expense by type of
      service and by age and gender category. The overall weighted average SAF is
      6.54%. SAFs are generally largest for ambulatory and smallest for hospital
      expenses. They are larger for males and for the older age categories. The model
      is analyzed for heteroscedasticity and goodness of fit. Additional analysis using
      the National Health Interview Survey is conducted to test for the possible effect
      of not being able to include alcohol consumption in the primary model. A balanced
      repeated replication analysis is conducted to evaluate the variance of the SAFs.
      Variances are found to be acceptably small. An extension of the model to support
      evaluation of smoking-attributable costs for special populations such as
      individual states, and special insurance pools such as Medicaid recipients, is
      described. Results for the fifty states are presented. Conclusions and subjects
      for further research are discussed.

PMID- 10077286
TI  - Medicine, economics and agenda-setting.
AB  - The filtering of potential policy issues from a large range of possibilities to a
      relatively small list of agenda items allows the organisation of power and
      influence within a policy sector to be examined. This study investigated power
      and influence in health policy agenda-setting in one State of Australia
      (Victoria) in the years 1991, 1992 and 1993. The actors seen as influential were
      predominantly medically trained and working in academia, health bureaucracies and
      public teaching hospitals. This research supports an elite model of health policy
      agenda-setting, in which outcomes are dependent on the structured interests
      within the policy field. However, while the corporate elite of the profession is
      influential, the frontline service providers are not, as indicated by the
      location of influentials in large and prestigious organisations. Politicians and
      professional associations and unions are less well represented, and consumer and
      community groups are virtually absent. In 1993 there was a sharp increase in
      economists being nominated as influentials, with a subsequent decrease in
      influentials with medical training. This relates to a (perceived or real) shift
      in influence from the medical profession to senior health bureaucrats. Economic
      concerns appear to be shaping the visible health policy agenda, through an
      increased number of influentials with economics training, but also through an
      apparent ability to shape the issues that other influentials are adding as agenda
      items. The corporate elite of medicine remains powerful, but their range of
      concerns has been effectively limited to cost containment or cost reduction,
      better planning and efficiency. This limiting of concerns occurs within an
      international policy context, where the general trends of globalisation and an
      emphasis on neo-liberal economics impact on the direction of health policy in
      individual countries.

PMID- 10077287
TI  - Dentistry and medical dominance.
AB  - In this study, I explore the relationship between medicine and dentistry in
      Ontario between 1868 and 1918. Examination of the rise of dentistry and medical
      dental relations reveals that medicine never came to dominate dentistry to the
      extent it did other health care occupations. The combination of four factors
      enabled dentistry to avoid outright medical dominance in Ontario. First,
      dentistry organized and professionalized at approximately the same time as did
      medicine in Ontario. Second, dentistry's jurisdiction remained somewhat separate
      from medicine's. Third, unlike other health care occupations, the dental
      profession never challenged medicine's claims to knowledge or expertise. Fourth,
      dental and medical leaders shared gender and class backgrounds, identities, and
      goals that discouraged conflict between them. The importance of these four
      factors and their implications for future research into inter-professional
      relations and medical dominance are discussed.

PMID- 10077288
TI  - Will the novel antipsychotics significantly ameliorate neuropsychological
      deficits and improve adaptive functioning in schizophrenia?

PMID- 10077289
TI  - Prevalence of suicide ideation and suicide attempts in nine countries.
AB  - BACKGROUND: There are few cross-national comparisons of the rates of suicide
      ideation and attempts across diverse countries. Nine independently conducted
      epidemiological surveys using similar diagnostic assessment and criteria provided
      an opportunity to obtain that data. METHODS: Suicide ideation and attempts were
      assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from
      the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan,
      Korea and New Zealand. RESULTS: The lifetime prevalence rates/100 for suicide
      ideation ranged from 2.09 (Beirut) to 18.51 (Christchurch, New Zealand). Lifetime
      prevalence rates/100 for suicide attempts ranged from 0.72 (Beirut) to 5.93
      (Puerto Rico). Females as compared to males had only marginally higher rates of
      suicidal ideation in most countries, reaching a two-fold increase in Taiwan.
      Females as compared to males had more consistently higher rates for suicide
      attempts, reaching a two- to three-fold increase in most countries. Suicide
      ideation and attempts in most countries were associated with being currently
      divorced/separated as compared to currently married. CONCLUSIONS: While the rates
      of suicide ideation varied widely by country, the rates of suicide attempts were
      more consistent across most countries. The variations were only partly explained
      by variation in rates of psychiatric disorders, divorce or separation among
      countries and are probably due to cultural features that we do not, as yet,
      understand.

PMID- 10077290
TI  - Manual-assisted cognitive-behaviour therapy (MACT): a randomized controlled trial
      of a brief intervention with bibliotherapy in the treatment of recurrent
      deliberate self-harm.
AB  - BACKGROUND: The treatment of deliberate self-harm (parasuicide) remains limited
      in efficacy. Despite a range of psychosocial, educational and pharmacological
      interventions only one approach, dialectical behaviour therapy, a form of
      cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but
      this is lengthy and intensive and difficult to extrapolate to busy clinical
      practice. We investigated the effectiveness of a new manual-based treatment
      varying from bibliotherapy (six self-help booklets) alone to six sessions of
      cognitive therapy linked to the booklets, which contained elements of dialectical
      behaviour therapy. METHODS: Thirty-four patients, aged between 16 and 50, seen
      after an episode of deliberate self-harm, with personality disturbance within the
      flamboyant cluster and a previous parasuicide episode within the past 12 months,
      were randomly assigned to treatment with manual-assisted cognitive-behaviour
      therapy (MACT N = 18) or treatment as usual (TAU N = 16). Assessment of clinical
      symptoms and social function were made at baseline and repeated by an independent
      assessor masked to treatment allocation at 6 months. The number and rate of all
      parasuicide attempts, time to next episode and costs of care were also
      determined. RESULTS: Thirty-two patients (18 MACT; 14 TAU) were seen at follow-up
      and 10 patients in each group (56% MACT and 71% TAU) had a suicidal act during
      the 6 months. The rate of suicidal acts per month was lower with MACT (median
      0.17/month MACT; 0.37/month TAU; P = 0.11) and self-rated depressive symptoms
      also improved (P = 0.03). The treatment involved a mean of 2.7 sessions and the
      observed average cost of care was 46% less with MACT (P = 0.22). CONCLUSIONS:
      Although limited by the small sample, the results of this pilot study suggest
      that this new form of cognitive-behaviour therapy is promising in its efficacy
      and feasible in clinical practice.

PMID- 10077291
TI  - The North Staffordshire Suicide Study: a case-control study of suicide in one
      health district.
AB  - BACKGROUND: The aim of the study was to identify sociodemographic and clinical
      risk factors for death from suicide and undetermined injury in residents of one
      health district. METHOD: Data were collected on all cases of suicide (ICD-9 E950
      959) and undetermined injury (ICD-9 E980-989) for residents in North
      Staffordshire Health District between 1991 and 1995. Controls identified from the
      Coroner's inquest register, who died from other causes, were matched for age and
      sex. RESULTS: Two hundred and twelve pairs of cases and matched controls were
      identified. Multivariate analysis (conditional logistic regression) showed that
      the risk of death due to suicide and undetermined death was associated with:
      recent separation, relationship difficulties, experience of financial
      difficulties, history of past criminal charges or contact with the police, a past
      history of deliberate self-harm, being on psychotropic medication at the time of
      death and a diagnosis of bipolar affective disorder. For sociodemographic
      variables, a univariate analysis found associations between the cases and being
      separated, living alone, having a past history of criminal charges and
      unemployment. Cases were more likely to have a psychiatric disorder, past history
      of deliberate self-harm and a past history of psychiatric contact for themselves
      or a family member. Controls were more likely to have a current medical disorder.
      Cases were more likely than controls to be on any form of medication at the time
      of death and to have received a prescription for psychotropic or non-psychotropic
      medication in the week and month before death. Cases were more likely than
      controls to have had contact with medical services in the week and month before
      death, with the general practitioner in the week before death and with
      psychiatric services at any time in the year before death. Strong associations
      were found between suicide and undetermined injury and life events such as recent
      separation and bereavement, and financial and relationship difficulties.
      CONCLUSIONS: The study provides an analytical investigation utilizing a dead
      control group, data gathered from several sources and adequate numbers of cases.
      It confirms many of the risk factors identified in other studies and highlights
      the high proportion of suicides who have been in recent contact with the criminal
      justice system or have been prescribed medication shortly before death.

PMID- 10077292
TI  - Acute tryptophan depletion in healthy young women with a family history of major
      affective disorder.
AB  - BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin
      synthesis, lowers mood in normal males with a multi-generational family history
      of major affective disorder (MAD) and in normal women devoid of any family
      history of psychiatric illness. As both a family history of MAD and female sex
      are factors predisposing to depression, the hypothesis that a mood lowering
      response to ATD may reflect a susceptibility to depression was further
      investigated in young women with an extensive, multi-generational family history
      of MAD. In addition, the temporal stability of mood change following repeated
      trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a
      tryptophan deficient amino acid mixture was ingested on two separate occasions.
      The control treatment, administered on a third occasion, was a nutritionally
      balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of
      plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the
      balanced condition, family history positive (FH +) women showed no lowering of
      mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood
      change between the two ATD trials (N = 13) exhibited poor temporal stability.
      CONCLUSIONS: These results may indicate that serotonin responsiveness is not an
      important characteristic of vulnerability to depression in these women.
      Alternately, these negative results may be due to the exclusion of a large number
      of FH + women who had already experienced an episode of depression, resulting in
      the selection of a biased FH + sample who are resistant to the mood lowering
      effects of ATD.

PMID- 10077293
TI  - Subclinical symptoms in mood disorders: pathophysiological and therapeutic
      implications.
AB  - BACKGROUND: The aim of this review was to survey the available literature on
      prodromal and residual symptoms of unipolar major depression and bipolar
      disorder. METHODS: Both a computerized (Medline) and a manual search of the
      literature were performed. RESULTS: In a substantial proportion of patients with
      affective disorders a prodromal phase can be identified. Most patients report
      residual symptoms despite successful treatment. Residual symptoms upon remission
      have a strong prognostic value. There appears to be a relationship between
      residual and prodromal symptomatology (the rollback phenomenon). CONCLUSIONS:
      Appraisal of subclinical symptomatology in mood disorders has important
      implications for pathophysiological models of disease and relapse prevention. In
      depression, specific treatment of residual symptoms may improve long-term
      outcome, by acting on those residual symptoms that progress to become prodromes
      of relapse. In bipolar disorder, decrease of subclinical fluctuations and
      improvement of level of functioning by specific therapeutic strategies may add to
      the benefits provided by lithium prophylaxis.

PMID- 10077294
TI  - Abnormal response to negative feedback in depression.
AB  - BACKGROUND: Recent studies have suggested that subjects with depression suffer a
      diagnosis-specific motivational deficit, characterized by an abnormal response to
      negative feedback that endures beyond clinical recovery. Furthermore, it has been
      suggested that negative feedback may motivate non-depressed controls, but not
      depressed patients, to improve their performance in neuropsychological tests.
      METHODS: We describe two studies. The first compared performance on the
      simultaneous and delayed match to sample (SDMS) task from the CANTAB
      neuropsychological test battery, in 20 patients with severe depression with 20
      with acute schizophrenia, 40 with chronic schizophrenia and 40 healthy controls.
      The second examined the performance of depressed patients with diurnal variation
      in symptoms and cognitive function. RESULTS: All patients groups showed
      impairments on the simultaneous and delayed match to sample task compared to
      controls. Depressed patients did not show an abnormal response to negative
      feedback. Controls did not show a motivational effect of negative feedback.
      Depressed patients with diurnal variation showed no variation in their response
      to perceived failure. There was no evidence of abnormal response to negative
      feedback in any patient group using the 'runs test' or of a motivational effect
      in controls. Conditional probability analysis was not independent of the total
      number of errors made in the SDMS task. CONCLUSIONS: Further studies are
      suggested to examine whether an abnormal response to negative feedback
      characterizes particular subgroups of patients suffering from depression.

PMID- 10077295
TI  - Cognitive function in depression: a distinct pattern of frontal impairment in
      melancholia?
AB  - BACKGROUND: Although depressed patients demonstrate impaired performance on a
      range of neuropsychological tests, there is little research that examines either
      frontal cognitive deficits or possible differences in test performance between
      melancholic and non-melancholic subtypes. METHODS: Depressed subjects were
      administered a broad neuropsychological battery. In an overall analysis, 77
      depressed subjects were compared with 28 controls. In a second set of analyses,
      the depressed sample was divided into melancholic and non-melancholic subsets
      according to DSM-III-R, the CORE system and the Newcastle scale. These depressed
      subsets were contrasted to controls and with each other using ANCOVA controlling
      for age, IQ, simple reaction time and Hamilton Depression scores where
      appropriate. RESULTS: The total depressed sample was impaired on most mnemonic
      tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R
      melancholic and non-melancholic subjects. When defined by the CORE and Newcastle
      (narrower definitions of melancholia), melancholic patients were additionally
      impaired on WCST (perseverative response) and (for Newcastle) digit symbol
      substitution. In contrast, the cognitive performance of the CORE and Newcastle
      defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using
      narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle,
      melancholic patients were impaired on mnemonic tasks and tasks of selective
      attention, and set-shifting while non-melancholic subjects were largely
      unimpaired in their cognitive performance. These differences may be due to
      impairment of specific neuroanatomical regions in narrowly defined melancholic
      patients, in particular the anterior cingulate.

PMID- 10077296
TI  - Post-traumatic stress disorder and major depression among Italian Nazi
      concentration camp survivors: a controlled study 50 years later.
AB  - BACKGROUND: The study aimed to assess the current and lifetime rates of post
      traumatic stress disorder (PTSD) and major depression (MDD) among Nazi
      concentration camps survivors. METHODS: We investigated 51 Italian political
      deportees and 47 Resistance Movement veterans who reported traumatic experiences
      during active service. The Structured Clinical Interview for DSM-IV was used to
      assess the presence of PTSD and MDD. The Dissociative Experiences Scale and the
      shorter version of the Hopkins Symptoms Checklist were also administered.
      RESULTS: The lifetime rates of PTSD and MDD were 35.3% and 45.1% respectively
      among deportees and 4.3% and 6.4% among former partisans. The current rates for
      PTSD and MDD were 25.5% and 33.3% among deportees and 4.3% and 4.3% among former
      partisans. Dissociative symptoms were more severe among deportees than among
      Resistance movement veterans. CONCLUSIONS: Concentration camp internment, even
      for political reasons, appears to have severe long-term psychiatric consequences.

PMID- 10077297
TI  - The onset of common mental disorders in primary care attenders in Harare,
      Zimbabwe.
AB  - BACKGROUND: This study aimed to investigate the onset and predictors of common
      mental disorders (CMD) in primary-care attenders in Harare, Zimbabwe. METHOD: Two
      (T1) and 12-month (T2) follow-up of a cohort of primary-care attenders without a
      common mental disorder (N = 197) as defined by the Shona Symposium Questionnaire
      (SSQ), recruited from primary health care clinics, traditional medical
      practitioner clinics and general practitioner surgeries. Outcome measure was
      caseness as determined by scores on the SSQ at follow-up. RESULTS: Follow-up rate
      was 86% at 2 months and 75% at 12 months. Onset of CMD was recorded in 16% at T1
      and T2. Higher psychological morbidity scores at recruitment, death of a first
      degree relative and disability predicted the presence of a CMD at both follow-up
      points. While female gender and economic difficulties predicted onset only in the
      short-term, belief in supernatural causation was strongly predictive of CMD at
      T2. Caseness at both follow-up points was associated with economic problems and
      disability at those follow-up points. CONCLUSIONS: Policy initiatives to reduce
      economic deprivation and targeting interventions to primary-care attenders who
      are subclinical cases and those who have been bereaved or who are disabled may
      reduce the onset of new cases of CMD. Closer collaboration between biomedical and
      traditional medical practitioners may provide avenues for developing methods of
      intervention for persons with supernatural illness models.

PMID- 10077298
TI  - Errorless learning and the cognitive rehabilitation of memory-impaired
      schizophrenic patients.
AB  - BACKGROUND: In recent years, evidence has accumulated that a significant
      proportion of schizophrenic patients have severe memory impairment, which cannot
      be attributed to the effects of medication, chronicity or institutionalization.
      Our group has demonstrated that memory impairment is associated with poor
      psychosocial outcome and treatment resistance. Work on the classical amnesic
      syndrome has suggested that memory training is facilitated by adopting an
      'errorless learning' approach, where subjects do not experience failure during
      learning. This is based on the theory that the preserved implicit memory of
      amnesic patients results in implicitly remembered incorrect responses interfering
      with target items, in the absence of a functioning explicit memory system to
      allow differentiation. METHOD: We compared three groups of subjects, memory
      impaired schizophrenic patients, memory unimpaired schizophrenic patients and
      healthy controls. RESULTS: An errorless learning approach conferred a significant
      advantage on the memory-impaired schizophrenic group, bringing their performance
      up to the level of both control groups. In contrast, adopting a traditional trial
      and error, or errorful approach resulted in markedly impaired performance in the
      memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless
      learning approaches may be worthy of further evaluation in the cognitive
      rehabilitation of memory-impaired schizophrenic patients.

PMID- 10077299
TI  - The impact of dementia on the detection of depression in elderly subjects from
      the general population.
AB  - BACKGROUND: The performance of the CES-D in a sample of elderly community
      residents was assessed. The influence of dementia on test performance and the
      necessity for the use of four factor scores instead of a single summary score of
      the CES-D were studied. METHOD: Two hundred and eighty-seven subjects out of the
      general population aged 60-99 years were personally interviewed with standardized
      diagnostic tools and completed the CES-D. Best-estimate diagnoses served as 'gold
      standards' for receiver operating characteristics (ROC) analysis. RESULTS: The
      CES-D discriminated well between depressive and non-depressive subjects.
      Exclusion of demented subjects from the sample did not markedly increase test
      performance. Current depressive illness and dementia led to high scores on the
      CES-D. Unlike the factors 'depressive affect', 'somatic/vegetative complaints',
      and 'interpersonal relations', the factor' positive affect' of the CES-D
      discriminated well between demented and non-demented participants. CONCLUSIONS:
      The CES-D is a valid instrument for screening for depression in a community
      sample of elderly subjects. Its use can be recommended even if the presence of
      dementia is likely. The use of factor scores of the CES-D does not substantially
      contribute to an improvement of overall test performance, but, nevertheless,
      allows a more detailed insight and better interpretation of test results.

PMID- 10077300
TI  - Can biased symptom perception explain false-alarm choking sensations?
AB  - BACKGROUND: Breathlessness in asthma often cannot be explained with objective
      variables indicating airways obstruction. The hypothesis that unrealistic
      breathlessness results from false interpretation of sensations was tested.
      METHODS: Sixty-four children and adolescents with asthma, aged 9-18 years, were
      randomly assigned to; (1) standardized physical exercise for induction of general
      symptoms; (2) equipment causing itching through skin irritation; or (3) physical
      exercise combined with equipment causing itching through skin irritation. Pre
      test and post-test measures were: lung function; breathlessness; general
      symptoms; itching; state anxiety; and worry. RESULTS: Lung function decreased
      within normal parameters (3.8%, 1.1%, 2.6%, respectively) and did not differ
      significantly between conditions. Breathlessness increased significantly after
      exercise, particularly in condition 3. Breathlessness correlated with general
      symptoms and worrying, but not with changes in lung function, age, or asthma
      severity. CONCLUSION: Biased symptom perception can explain unrealistic
      breathlessness. Prerequisites are situational cues triggering selective
      perception and ambiguous sensations associated with the anticipated (feared)
      physical state. Excessive breathlessness may often warrant objective confirmation
      by means of lung-function testing.

PMID- 10077301
TI  - Confirmatory factor analysis of the Parental Bonding Instrument in a Japanese
      population.
AB  - BACKGROUND: There is controversy surrounding the factor structure of the Parental
      Bonding Instrument (PBI), a widely used instrument for assessing perceived
      parental rearing behaviours. Recent studies have proposed five different factor
      structures, including Parker et al.'s original two-factor model. METHODS: Four
      hundred and eighteen employed Japanese adults filled out the PBI. Maximum
      likelihood confirmatory factor analyses were performed to compare the five
      different factor structures in terms of model-fit. RESULTS: Parker's original two
      factor structure fitted the data poorly. In general, three-factor structures
      showed better fit. Among the three-factor structures, Murphy's model and
      Kendler's model were superior (the adjusted goodness-of-fit index > 0.8), with
      the latter providing the best fit to the data (the goodness-of-fit index > 0.9).
      When considering invariance of factor structure across gender subgroups and
      across age subgroups, only Kendler's model was acceptable. CONCLUSIONS: Parker's
      two-factor structure of the PBI may not be appropriate for assessing perceived
      parental rearing behaviours in a Japanese population. Three-factor structures, in
      particular Murphy's model and Kendler's model, are preferable. Kendler's model
      provided the best fit to the data and was relatively invariant across the
      subgroups in this study. Thus, Kendler's model might prove to be very important
      for obtaining a factor structure invariant across different cultures.

PMID- 10077302
TI  - The generation of life events in recurrent and non-recurrent depression.
AB  - BACKGROUND: The stress generation hypothesis proposed by Hammen (1991) holds that
      depressed individuals generate stressful conditions for themselves, which lead to
      recurrence. The original test of this hypothesis compared dependent life events
      in women with recurrent depression to medical and normal controls. Two further
      research questions emerged from this work: (a) do individuals with a history of
      many depressive episodes generate more dependent life events than depressives
      with fewer episodes?; and (b) what is the aetiological relevance of any stress
      that may be generated? METHODS: The present research tested differences in
      dependent and independent events between depressed individuals who had
      experienced: (a) no previous major depressive episodes; (b) one previous episode;
      and (c) two or more previous episodes. We predicted that, based on the stress
      generation hypothesis, recurrent depressives would show more dependent events
      than people without a depression history, and that these generated stressors
      would be of aetiological importance for precipitating recurrence (i.e. severe
      events in the 3 months preceding recurrence). RESULTS: Recurrent depressives
      experienced significantly more total dependent events than first-onset
      depressives in the 12 months, but not the 3 months, preceding their episode.
      CONCLUSIONS: Although the findings supported the general premise of stress
      generation, the aetiological relevance of the generated stress for recurrence
      requires further study.

PMID- 10077303
TI  - A date to remember: the nature of memory in savant calendrical calculators.
AB  - BACKGROUND: Savant calendar calculators can supply with speed the day of the week
      of a given date. Although memory is suggested to be an important component of
      this unusual ability, memory function has never been systematically investigated
      in these skilled yet learning impaired individuals. METHODS: Eight savant
      calendrical calculators, most of whom had autism, were compared with eight verbal
      IQ, age and diagnosis matched controls on digit and word span tests and measures
      of long-term memory for words and calendrical information (individual years). In
      an analogue to the 'generation effect', the savants' memory for dates was also
      compared following calculation and study/read tasks. RESULTS: The savants did not
      differ from controls on measures of general short- and long-term memory. They
      did, however, show a clear recall superiority for the long-term retention of
      calendrical material. They also remembered calculated dates better than those
      that were only studied. CONCLUSIONS: A general mnemonic advantage cannot explain
      savant date calculation skills. Rather, through exposure to date information, the
      savants are suggested to develop a structured calendar-related knowledge base
      with the process of calculation utilizing the interrelations within this
      knowledge store. The cognitive processing style characteristic of autism may also
      play a role in the acquisition of this savant ability.

PMID- 10077304
TI  - Increased automatic spreading activation in healthy subjects with elevated scores
      in a scale assessing schizophrenic language disturbances.
AB  - BACKGROUND: Previous studies on semantic priming have suggested that
      schizophrenic patients with language disturbances demonstrate enhanced semantic
      and indirect semantic priming effects relative to controls. However, the
      interpretation of semantic priming studies in schizophrenic patients is obscured
      by methological problems and several artefacts (such as length of illness). We,
      therefore, used a psychometric high-risk approach to test whether healthy
      subjects reporting language disturbances resembling those of schizophrenics (as
      measured by the Frankfurt Complaint Questionnaire subscale 'language') display
      increased priming effects. In addition, the Schizotypal Personality Questionnaire
      was used to cover symptoms of schizotypal personality. Enhanced priming was
      expected to occur under conditions favouring automatic processes. METHODS: One
      hundred and sixty healthy subjects performed a lexical decision semantic priming
      task containing two different stimulus onset asynchronicities (200 ms and 700 ms)
      with two experimental conditions (semantic priming and indirect semantic priming)
      each. RESULTS: Analyses of variance revealed that the Frankfurt Complaint
      Questionnaire-' language' high scorers significantly differed from low scorers in
      three of the four priming conditions indicating increased automatic spreading
      activation. No significant results were obtained for the Schizotypal Personality
      Questionnaire total and subscales scores. CONCLUSIONS: In line with Maher and
      Spitzer it is suggested that increased automatic spreading activation underlies
      schizophrenia-typical language disturbances which in our study cannot be
      attributed to confounding variables such as different reaction time baselines,
      medication or length of illness. Finally, results confirm that the psychometric
      high-risk approach is an important tool for investigating issues relevant to
      schizophrenia.

PMID- 10077305
TI  - HIV-risk behaviour and knowledge about HIV/AIDS among patients with
      schizophrenia.
AB  - BACKGROUND: Recent literature has demonstrated that psychiatric patients,
      particularly those with a diagnosis of schizophrenia, may be at high risk for HIV
      infection. In fact, HIV-risk behaviour, such as intravenous drug with sharing
      needles, promiscuity associated with unprotected sex and high-risk sexual
      activity after using drugs has been reported by a substantial proportion of
      mentally ill patients. METHODS: In order to examine this problem in Italy, HIV
      risk taking behaviour and knowledge about HIV/AIDS was investigated among 91
      schizophrenic patients by using two self-report questionnaires (HIV-Risk
      Behaviour Questionnaire; AIDS-Risk Behaviour Knowledge Test). RESULTS: One-third
      of the patients reported having been tested for HIV infection and one tested
      seropositive (prevalence 3.4%). A high proportion of patients reported HIV-risk
      behaviour, such as injected drugs use (22.4%) and engaging in high risk sexual
      activity (e.g. multiple partners, 58%; prostitutes, 45%; occasional partners,
      37%). Condoms were 'never used' by 41% of the patients and 'almost never used' by
      another 25%. In spite of these behaviours, 65% reported no concern of HIV
      infection. Knowledge about AIDS was lower among psychiatric patients than a
      healthy control group. Patients with long-lasting illness and numerous
      psychiatric admissions were less acknowledgeable about HIV infection. Certain
      misconceptions on HIV transmission were related to HIV risk behaviour.
      CONCLUSIONS: These results indicate the urgent need for HIV educational
      programmes within mental health community-care settings.

PMID- 10077306
TI  - Magnetic resonance imaging differences between dementia with Lewy bodies and
      Alzheimer's disease: a pilot study.
AB  - BACKGROUND: Temporal lobe atrophy on magnetic resonance imaging (MRI) has been
      suggested as a specific diagnostic marker for Alzheimer's disease (AD). No
      previous comparison with dementia with Lewy bodies (DLB) has been reported.
      METHOD: T1-weighted MRI scans were performed on 11 subjects with AD (nine with
      NINCDS/ADRDA probable AD and two with neuropathologically proven AD) and nine
      subjects with DLB (four with probable DLB diagnosed by clinical criteria and five
      with neuropathologically proven DLB). Groups were matched for age, duration of
      illness and cognitive test score. Two raters, blind to diagnosis and
      neuropathological findings, measured the volumes of the frontal lobes, temporal
      lobes, hippocampi, parahippocampal gyri, amygdalae, and caudate nuclei using a
      computerized volumetric analysis system. Scans were also rated for medial
      temporal atrophy on a four-point scale by an experienced rater. RESULTS: AD
      subjects had significantly smaller left temporal lobes and parahippocampal gyri
      than those with DLB. Medial temporal atrophy was present in 9/11 AD cases (82%)
      and absent in 6/9 (67%) of DLB cases. Two neuropathologically confirmed cases of
      DLB had severe medial temporal atrophy; both had concurrent AD-type pathology in
      the temporal lobe (Braak stage 4). CONCLUSIONS: This pilot study supports the
      hypothesis that a greater burden of pathology centres on the temporal lobes in AD
      compared with DLB, except in DLB cases with concurrent Alzheimer pathology. A
      larger study is needed to confirm these findings and to determine whether MRI has
      a role in assisting with the clinical differentiation between DLB and AD.

PMID- 10077307
TI  - Immediate memory, attention and communication disturbances in schizophrenia
      patients and their relatives.
AB  - BACKGROUND: Schizophrenia has been defined in part by disturbances of thought and
      language. The non-schizophrenic relatives of patients also have been found to
      show subtle disturbances of language that may be associated with vulnerability.
      Investigators have hypothesized that these phenomena in patients and their
      relatives are, at least in part, the result of weaknesses in facets of attention
      and memory. METHODS: The present study assessed some neuropsychological process
      correlates of three different measures of thought and language symptoms in 55
      stable out-patients, using tests of immediate auditory memory impairment and
      auditory distractability, and carefully controlling for generalized deficit
      effects. A parallel assessment was made of referential communication disturbances
      in 59 non-schizophrenic relatives of patients and 24 control subjects matched to
      the relatives. RESULTS: In patients, formal thought disorder, disorganization,
      and referential communication disturbances were all associated with each other
      and with auditory distractability. In addition, as expected, referential
      communication disturbances were associated with immediate auditory memory
      impairment. Referential disturbance ratings for relatives were similar in
      magnitude to those for the stable out-patients, and much higher than for
      controls. However, the relatives' language ratings were not associated
      specifically with weaknesses in attention or memory as measured. CONCLUSIONS:
      Impairments in immediate auditory memory and attention are associated
      differentially with different types of communication disturbances in
      schizophrenia patients. The cognitive substrate for referential communication
      disturbances in relatives appears to differ qualitatively from that for patients.

PMID- 10077308
TI  - Psychometric properties of the Liebowitz Social Anxiety Scale.
AB  - BACKGROUND: The present study provides data on the reliability, validity and
      treatment sensitivity of the Liebowitz Social Anxiety Scale (LSAS), one of the
      most commonly used clinician-administered scales for the assessment of social
      phobia. METHOD: Three hundred and eighty-two patients from several studies of the
      treatment of social phobia were evaluated. An independent assessor administered
      the LSAS to each patient prior to the initiation of treatment. Patients also
      completed other measures of social anxiety and avoidance, although the specific
      measures varied across samples. RESULTS: The LSAS and its subscales were normally
      distributed and demonstrated excellent internal consistency. The convergent
      validity of the LSAS was demonstrated via significant correlations with other
      commonly-used measures of social anxiety and avoidance. These correlations also
      tended to be larger than correlations with measures of depression, especially
      after treatment. However, the pattern of correlations of LSAS subscales with one
      another and with the other measures suggest that the fear subscales and the
      avoidance subscales may not be sufficiently distinct in clinical samples. The
      LSAS was also demonstrated to be sensitive to the effects of pharmacological
      treatments of social phobia over time and in comparison to double-blind pill
      placebo. CONCLUSION: The LSAS appears to be a reliable, valid and treatment
      sensitive measure of social phobia. Further study of the LSAS, both in samples
      with severe social phobia and in community samples, is needed.

PMID- 10077309
TI  - Conditions not attributable to a mental disorder in Dutch psychiatric out
      patients.
AB  - BACKGROUND: According to DSM-III-R V-code conditions refer to marital
      relationships, family circumstances, interpersonal relationships, or stressful
      life events that are not attributable to a mental disorder but that are the focus
      of treatment. The purpose of the present study was to assess the prevalence and
      patient and treatment characteristics of adult psychiatric out-patients diagnosed
      with V-code conditions. METHODS: The records of all 5660 consecutive admissions
      to a psychiatric out-patient clinic over a 12-year period were studied
      retrospectively. On the basis of both primary and secondary DSM-III-R diagnoses
      on Axis I, two subgroups of patients were compared: (1) patients with V-code
      conditions; and (2) patients with mental disorders. RESULTS: Fourteen per cent of
      the patients had a V-code condition and no mental disorder, while the remaining
      patients were diagnosed with mental disorder (with or without an additional V
      code condition). Comparisons of sociodemographic and clinical severity
      characteristics of the two groups indicated that patients with V-code conditions
      tended to have a higher socio-economic status and to present with less severe
      problems as assessed both by the primary therapist and the Symptom-Checklist-90.
      With respect to service use and treatment outcome variables, it appeared that V
      code patients tended to be more frequently treated by couple/family therapy and
      to receive a slightly lower number of treatment sessions. CONCLUSIONS: The
      pattern of results in The Netherlands seems comparable to results of previous
      North American studies. Implications of these findings for future studies and for
      use of mental health services are discussed.

PMID- 10077310
TI  - The views and outcomes of consenting and non-consenting patients receiving ECT.
AB  - BACKGROUND: Current mental health legislation in the UK makes provision for the
      use of certain treatments in severely ill patients who are unable, or unwilling,
      to give informed consent. Under the terms of this legislation, electroconvulsive
      therapy (ECT) may be used, usually to treat severely depressed patients. A number
      of organizations have challenged this practice, stating that ECT should only be
      given with fully informed consent: it has been implied that patients receiving
      compulsory ECT (given without the patient's consent, under the terms of mental
      health legislation) find the treatment damaging and unhelpful. METHODS: A series
      of 150 patients receiving ECT in Aberdeen was studied. A proportion of the series
      (approximately 7%) received compulsory ECT. The views and treatment outcomes of
      compulsory patients were compared with those of patients giving informed consent
      for treatment. RESULTS: More than 80% of patients in both consenting and
      compulsory groups considered ECT to have helped them. Clinical outcome did not
      differ between the groups. Patients' views showed marked concordance with
      independent medical evaluation of outcome. CONCLUSIONS: Outcome following ECT in
      non-consenting patients is equivalent to that seen in consenting patients whether
      rated by the patients themselves or by clinicians. Overall outcome is good, with
      more than 80% of patients benefiting from treatment. A ban on compulsory ECT
      would deny the access of seriously ill patients to an effective and acceptable
      treatment.

PMID- 10077311
TI  - Long-term effects of alprazolam on memory: a 3.5 year follow-up of
      agoraphobia/panic patients.
AB  - BACKGROUND: Benzodiazepines (BZs) can impair explicit memory after a single dose
      and also when taken repeatedly for treatment of anxiety disorders. A previous
      study with agoraphobia/panic patients found that the BZ alprazolam impaired
      memory during an 8-week treatment and residual impairments were still manifest
      several weeks after drug withdrawal (Curran et al. 1994). The present study
      followed up the same group of patients 3.5 years after treatment to determine
      whether those memory impairments persisted. METHOD: Thirty-one patients, 15 who
      had originally been treated with alprazolam and 16 with placebo, were assessed on
      a battery of psychometric tests and self-rating scales. RESULTS: Ex-alprazolam
      patients performed at the same levels as ex-placebo patients on the memory task
      and on other objective tests. Performance levels of both groups were similar to
      pre-treatment baselines, however there were differences in subjective ratings
      whereby ex-alprazolam patients rated themselves as less attentive and clear
      headed and more incompetent and clumsy than ex-placebo patients. CONCLUSIONS:
      Explicit memory impairments found while patients were taking alprazolam and weeks
      after drug withdrawal did not persist 3.5 years later. We suggest that the memory
      impairments observed in our previous study weeks after withdrawal of alprazolam
      were not residual effects of alprazolam but rather were due to the drug's
      interference with practice effects on the tests and habituation of anxiety over
      repeated exposure to the test situation.

PMID- 10077312
TI  - Panic disorder following torture by suffocation is associated with predominantly
      respiratory symptoms.
AB  - BACKGROUND: We previously reported that in panic disorder a history of near
      suffocation is associated with predominantly respiratory panic attacks. It might
      be hypothesized that the near-suffocation experienced in certain kinds of torture
      is also associated with the development of predominantly respiratory panic
      attacks. METHODS: A sample of patients who had experienced torture (N = 14) was
      drawn from an Anxiety Disorders Clinic in South Africa. Subjects were questioned
      about symptoms of panic disorder, posttraumatic stress disorder and depression.
      RESULTS: Patients with a history of torture by suffocation were more likely than
      other patients to complain of predominantly respiratory symptoms during panic
      attacks. These patients also demonstrated higher levels of depressive symptoms.
      CONCLUSIONS: While various interpretations of the data can be made, it is
      possible that torture by suffocation is associated with a specific symptomatic
      profile. Were such an association to be replicated, this would perhaps support
      the suffocation alarm hypothesis of panic disorder and provide evidence that
      specific environmental factors play a role in the development of this alarm.

PMID- 10077313
TI  - Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out
      mice.
AB  - Nitric oxide is formed in the brain primarily by neurons containing neuronal
      nitric oxide synthase (nNOS), though some neurons may express endothelial NOS
      (eNOS), and inducible NOS (iNOS) only occurs in neurons following toxic stimuli.
      Mice with targeted disruption of nNOS (nNOS-) display distended stomachs with
      hypertrophied pyloric sphincters reflecting loss of nNOS in myenteric plexus
      neurons. nNOS- animals resist brain damage following middle cerebral artery
      occlusions consistent with evidence that excess release of nitric oxide mediates
      neurotoxicity in ischemic stroke. Neuronal NOS- mice have no grossly evident
      defects in locomotor activity, breeding long-term depression in the cerebellum,
      long-term potentiation in the hippocampus, and overall sensorimotor function.
      However, nNOS- animals display excessive, inappropriate sexual behavior and
      dramatic increases in aggression. Because the cerebellum possesses the greatest
      levels of nNOS neurons in the brain, it was surprising that presumed cerebellar
      functions such as balance and coordination were grossly normal in nNOS- mice.
      These previous studies were all conducted during the day (between 1400 and 1600,
      lights on at 0700). We now report striking, discrete abnormalities in balance and
      motor coordination in nNOS-mice reflected selectively at night.

PMID- 10077314
TI  - Endomorphin-like immunoreactivity in the rat dorsal horn and inhibition of
      substantia gelatinosa neurons in vitro.
AB  - Endomorphin 1 and 2 are two tetrapeptides recently isolated from bovine as well
      as human brains and proposed to be the endogenous ligand for the mu-opiate
      receptor. Opioid compounds expressing mu-receptor preference are generally potent
      analgesics. The spinal cord dorsal horn is considered to be an important site for
      the processing of sensory information including pain. The discovery that
      endomorphins produced greater analgesia in mice upon intrathecal as compared to
      intracerebroventricular injections raises the possibility that dorsal horn
      neurons may represent the anatomic site upon which endomorphins exert their
      analgesic effects. We report here the detection of endomorphin 2-immunuoreactive
      fiber-like elements in superficial layers of the rat dorsal horn by
      immunohistochemical techniques. Whole-cell patch recordings from substantia
      gelatinosa neurons of cervical spinal cord slices revealed two conspicuous
      effects of exogenously applied endomorphin 1 and 2: (i) depression of excitatory
      postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (ii)
      hyperpolarization of substantia gelatinosa neurons. These effects were reversed
      by the selective mu-opiate receptor antagonist beta-funaltrexamine. Collectively,
      the detection of endomorphin-like immunoreactivity in nerve fibers of the
      superficial layers and the inhibitory action of endomorphins on substantia
      gelatinosa neurons provide further support for a potential role of these two
      peptides in spinal nociception.

PMID- 10077315
TI  - Conditioned and unconditioned aversive stimuli enhance light-induced fos
      expression in the primary visual cortex.
AB  - Studies in rats indicate that photic responses within the dorsal lateral
      geniculate nucleus can be enhanced in response to stimuli known to induce
      negative emotional arousal. Little is known, however, about the effect of such
      stimuli on photic responses within primary visual cortex, the principal
      projection area of the dorsal lateral geniculate. Here, we examined the effect of
      unconditioned and conditioned aversive stimuli on photic responses within the
      primary visual cortex in rats using expression of the transcription factor Fos as
      a functional marker of neuronal activation. In previous studies carried out
      within the circadian visual system, we found that photic induction of Fos within
      the principal target area of the circadian visual pathway, the suprachiasmatic
      nucleus of the hypothalamus, was attenuated when the light stimulus was given
      concurrently with an aversive footshock or was made an aversive conditioned
      stimulus through previous pairings with footshock. In addition, we found that
      photic stimulation of Fos expression in the suprachiasmatic nucleus was
      attenuated in a context made aversive through previous pairings with footshock.
      We now report that in these same animals, unlike what was seen within the
      suprachiasmatic nucleus, Fos expression in the primary visual cortex is
      significantly elevated. These findings support the view that emotional arousal
      can enhance the response of cells in the visual cortex to photic input, and point
      to the differential effect of aversive emotional events on photic responses
      within pathways underlying visual perception and those involved in circadian
      regulation.

PMID- 10077316
TI  - Heparin injection into the adult rat hippocampus induces seizures in the absence
      of macroscopic abnormalities.
AB  - The pathological hallmarks of Alzheimer's disease include neurofibrillary
      tangles, neuropil threads and neuritic plaques. Neurofibrillary tangles and
      neuropil threads are comprised of paired helical filaments which are themselves
      composed of a hyperphosphorylated form of the microtubule-associated protein tau.
      Neuritic plaques are extracellular deposits of aggregated beta amyloid associated
      with neurites containing hyperphosphorylated tau. The mechanisms by which the
      neurofibrillary tangles and neuritic plaques develop in Alzhemier's disease are
      not clear but it is hypothesized that sulphated glycosaminoglycans are important
      in their formation. This impression is based on the finding that the
      glycosaminoglycan, heparan sulphate, is found associated with neurofibrillary
      tangles, neuritic plaques and neuropil threads while dermatan sulphate,
      chondroitin sulphate and keratan sulphate immunoreactivity is found around
      neuritic plaques in brains of Alzheimer's disease patients. Furthermore, in vitro
      studies demonstrate that sulphated glycosaminoglycans such as heparan sulphate
      and the closely related molecule heparin interact with tau and potentiate its
      phosphorylation by a number of serine/threonine kinases, reduce its ability to
      bind to microtubules and induce paired helical filament formation, all properties
      associated with tau isolated from Alzheimer's disease brain. Thus, we were
      interested to learn whether intracerebral injection of the sulphated
      glycosaminoglycan heparin would give rise to alterations in the cytoskeletal
      protein tau in the rat brain. Although no cytoskeletal changes were observed, to
      our considerable surprise we found that the intrahippocampal injection of heparin
      gave rise to seizures. We have investigated this unexpected effect further in
      vivo and by using in vitro electrophysiological techniques.

PMID- 10077317
TI  - The basic mechanism for the electrical stimulation of the nervous system.
AB  - Neural signals can be generated or blocked by extracellular electrodes or
      magnetic coils. New results about artificial excitation are based on a
      compartmental model of a target neuron and its equivalent electrical network, as
      well as on the theory of the generalized activating function. The analysis shows
      that: (i) in most cases, the origin of artificial excitation is within the axon
      and the soma is much more difficult to excite; (ii) within the central nervous
      system, positive and negative threshold currents essentially depend on the
      position and orientation of the neurons relative to the applied electric field;
      (iii) in several cases, stimulation with positive currents is easier; and (iv) it
      should be possible to excite synaptic activity without the generation of
      propagating action potentials. Furthermore, the theory of the generalized
      activating function gives hints to understanding the blockage of neural activity.

PMID- 10077318
TI  - Fast burst firing and short-term synaptic plasticity: a model of neocortical
      chattering neurons.
AB  - We present an ionic conductance model of chattering neurons in the neocortex,
      which fire fast rhythmic bursts in the gamma frequency range (approximately 40
      Hz) in response to stimulation [Gray C. M. and McCormick D. A. (1996) Science
      274, 109-113]. The bursting mechanism involves a "ping-pong" interplay between
      soma-to-dendrite back propagation of action potentials and an afterdepolarization
      generated by a persistent dendritic Na+ current and a somatic Na+ window current.
      The oscillation period is primarily determined by a slowly inactivating K+
      channel and passive membrane properties. The model behavior is compared
      quantitatively with the experimental data. It is shown that the cholinergic
      muscarinic receptor activation can transform the model cell's firing pattern from
      tonic spiking to rapid bursting, as a possible pathway for acetylcholine to
      promote 40-Hz oscillations in the visual cortex. To explore possible functions of
      fast burst firing in the neocortex, a hypothetical neural pair is simulated,
      where a chattering cell is presynaptic to an inhibitory interneuron via
      stochastic synapses. For this purpose, we use a synapse model endowed with a low
      release probability, short-term facilitation and vesicle depletion. This synapse
      model reproduces the behavior of certain neocortical pyramid-to-interneuron
      synapses [Thomson A. M. et al. (1993) Neuroscience 54, 347-360]. We showed that
      the burstiness of cell firing is required for the rhythmicity to be reliably
      transmitted to the postsynaptic cell via unreliable synapses, and that fast burst
      firing of chattering neurons can provide an exceptionally powerful drive for
      recruiting feedback inhibition in cortical circuits. From these results, we
      propose that the fast rhythmic burst firing of neocortical chattering neurons is
      generated by a calcium-independent ionic mechanism. Our simulation results on the
      neural pair highlight the importance of characterizing the short-term plasticity
      of the synaptic connections made by chattering cells, in order to understand
      their putative pacemaker role in synchronized gamma oscillations of the visual
      cortex.

PMID- 10077319
TI  - Transgenic ablation of rod photoreceptors alters the circadian phenotype of mice.
AB  - The impact of photoreceptor loss on the circadian system was examined by
      utilizing a transgenic mouse model (rdta) in which rod photoreceptors were
      specifically ablated. These mice were able to phase-shift their circadian
      locomotor behaviour in response to light, but features of this circadian
      behaviour were markedly altered. The amplitude of circadian responses to light
      were approximately 2.5 greater, the circadian period (tau) was reduced (c. 20
      min) and the total duration of activity (alpha) was increased (c. 50 min) when
      compared to wild type (+/+) and rd/rd mice (retinal degeneration, mice which also
      lack rod photoreceptors) of the same genetic background. The pattern of Fos
      expression in the suprachiasmatic nuclei (the site of the primary circadian clock
      in mammals) was indistinguishable between +/+ and rdta mice. However, Fos
      expression in the retina suggested that rod loss in rdta mice resulted in a
      functional reorganization of the retina and the constitutive activation of a
      population of retinal ganglion cells. Although it has been known for several
      years that the entraining photoreceptors of mammals are ocular, and that rod
      photoreceptors are not required for light regulation of the clock, these are the
      first data to show that features of the circadian phenotype (amplitude of the
      phase response curve, alpha, tau) can be influenced by photoreceptor ablation.
      These data support the hypothesis that the circadian phenotype of mammals is the
      product of an interaction between the suprachiasmatic nuclei and the retina.
      Thus, mammals which show an altered circadian behaviour can no longer be assumed
      to have defects associated only with specific clock genes; genes that affect
      photoreceptor survival may also modify circadian behaviour.

PMID- 10077320
TI  - Vasopressin-deficient suprachiasmatic nucleus grafts re-instate circadian
      rhythmicity in suprachiasmatic nucleus-lesioned arrhythmic rats.
AB  - It was investigated whether grafts of the suprachiasmatic nucleus could re
      instate circadian rhythmicity in the absence of its endogenous vasopressin
      production and whether the restored rhythm would have the long period length of
      the donor. Grafts of 17-days-old vasopressin-deficient homozygous Brattleboro rat
      fetuses, homotopically placed in arrhythmic suprachiasmatic nucleus-lesioned
      Wistar rats, re-instated circadian drinking rhythm within 20-50 days similar as
      seen for grafts of heterozygous control fetuses. Period length of the recovered
      rhythm revealed a similar difference (average 24.3 vs. 23.8 h) as reported for
      the rhythm between the adult Brattleboro genotypes. In all transplants, also
      those of the two-third non-recovery rats, a surviving suprachiasmatic nucleus was
      visible as a vasoactive intestinal polypeptide-positive neuronal cell cluster,
      whereas heterozygous transplants also revealed the complementary vasopressinergic
      cell part. Explanation of the absence of recovery failed since no undisputable
      correlation emerged between recovery of rhythm and vasoactive intestinal
      polypeptide, vasopressin and/or somatostatin immunocytochemical characteristics
      of the suprachiasmatic nucleus of the transplant. Special focus on the
      somatostatinergic neurons revealed their presence only occasionally near or in
      between the vasoactive intestinal polypeptidergic and (in the case of
      heterozygous grafts) vasopressinergic cell cluster. However their aberrant
      cytoarchitectural position appeared not to have affected the possibility to
      restore drinking rhythm of the suprachiasmatic nucleus-lesioned arrhythmic rat.
      It was concluded that grafted Brattleboro fetal suprachiasmatic nucleus develop
      their intrinsic rhythm conform their genotype and that vasopressin is not a
      crucial component in the maintenance nor in the transfer of circadian activity of
      the biological clock for drinking activity. Vasopressin of the suprachiasmatic
      nucleus may instead serve modulation within the circadian system.

PMID- 10077321
TI  - Expression of basic helix-loop-helix/PAS genes in the mouse suprachiasmatic
      nucleus.
AB  - The suprachiasmatic nuclei contain a circadian clock that drives rhythmicity in
      physiology and behavior. In mice, mutation of the Clock gene produces abnormal
      circadian behavior [Vitaterna M. H. et al. (1994) Science 264, 715-725]. The
      Clock gene encodes a protein containing basic helix-loop-helix and PAS (PER-ARNT
      SIM) domains [King D. P. et al. (1997) Cell 89, 641-653]. The PAS domain may be
      an important structural feature of a subset of genes involved in photoreception
      and circadian rhythmicity. The expression and regulation of messenger RNAs
      encoding eight members of the basic helix-loop-helix/PAS protein superfamily were
      examined by in situ hybridization. Six of the genes studied (aryl hydrocarbon
      receptor nuclear transporter, aryl hydrocarbon receptor nuclear transporter-2,
      Clock, endothelial PAS-containing protein, hypoxia-inducible factor-1alpha and
      steroid receptor coactivator-1) were expressed in the suprachiasmatic nucleus of
      adult and neonatal mice. No evidence for rhythmicity of expression was observed
      when comparing brains collected early in the subjective day (circadian time 3)
      with those collected early in subjective night (circadian time 15). Neuronal PAS
      containing protein-1 messenger RNA was expressed in the suprachiasmatic nucleus
      of adult (but not neonatal) mice, and a low-amplitude rhythm of neuronal PAS
      containing protein-1 gene expression was detected in the suprachiasmatic nucleus.
      Neuronal PAS-containing protein-2 messenger RNA was not detected in adult or
      neonatal suprachiasmatic nucleus. Exposure to light at night (30 or 180 min of
      light, beginning at circadian time 15) did not alter the expression of any of the
      genes studied. The expression of multiple members of the basic helix-loop
      helix/PAS family in the suprachiasmatic nucleus suggests a rich array of
      potential interactions relevant to the regulation of the suprachiasmatic
      circadian clock.

PMID- 10077322
TI  - Fast retrograde effects on neuronal death and dendritic organization in
      development: the role of calcium influx.
AB  - Retrograde signals from axon terminal to cell body are known to regulate neuronal
      survival and differentiation during development. They are generally attributed to
      the uptake and transport of trophic factors, but there is recent evidence in the
      isthmo-optic nucleus for a remarkably fast-acting retrograde signal from the
      contralateral retina that is not mediated by the conventional trophic route. The
      isthmo-optic nucleus undergoes 55% neuron death between embryonic days 12 and 17,
      and becomes laminated at embryonic day 14 owing to dendritic re-organization.
      Blockade of retinal electrical activity just before day 14 reduces neuronal death
      and lamination in the isthmo-optic nucleus within as little as 6 h. We here
      investigate how action potentials initiate the fast-acting retrograde signal, and
      we provide evidence that the first step is calcium entry into the isthmo-optic
      axon terminals. Neuronal death and lamination are rapidly reduced in the isthmo
      optic nucleus by intraocularly injected omega-conotoxin, a blocker of N-type
      calcium channels known to be located mainly on axon terminal. Similar effects
      occurred with two other calcium channel blockers (cadmium and alpha-bungarotoxin)
      believed to act on both the isthmo-optic terminals and their target cells, but
      not with nifedipine, a blocker of L-type (mainly somatic) channels, supporting a
      presynaptic initiation of the fast signal. Nevertheless postsynaptic events may
      also be involved because pharmacological destruction of the amacrine targets
      cells of the isthmo-optic nucleus reduced its cell death and lamination 9-12 h
      later.

PMID- 10077323
TI  - Transplants of fetal frontal cortex grafted into the occipital cortex of newborn
      rats receive a substantial thalamic input from nuclei normally projecting to the
      frontal cortex.
AB  - A number of molecular and hodological experiments have provided evidence that
      there is an early commitment of neocortical neurons to express features unique to
      a certain cortical area. However, the findings of several transplantation
      experiments have indicated that late embryonic cortical tissue heterotopically
      grafted into the neocortex of newborn rats receives a set of thalamic projections
      appropriate for the host cortical locus within which it develops. To provide
      further information on the extent to which neocortical neurons are predetermined
      to develop area-specific systems of connections, in this study we have compared
      the pattern of thalamic afferents to grafts of embryonic day 16 occipital or
      frontal neocortex transplanted into the occipital cortex of newborn rats. Two
      months after grafting, a retrograde neurotracer (cholera toxin, subunit b) was
      injected into the grafts to precisely assess the number of cells in the visual-
      and/or motor-related nuclei of the host thalamus projecting to each category of
      transplants (occipital-to-occipital or frontal-to-occipital). Transplants of
      embryonic occipital cortex received significant input from several visual-related
      thalamic nuclei, i.e. the lateral posterior and lateral dorsal nuclei, and no
      input from motor-related thalamic nuclei. However, only few labeled cells were
      found in the dorsal lateral geniculate nucleus, which was systematically affected
      by a severe atrophy, probably in response to the lesion of the occipital cortex
      performed prior to the transplantation. By comparison, transplants of frontal
      origin received a substantial input from the ventrolateral and ventromedial
      thalamic nuclei, which normally project to the frontal cortex, but received a
      weak input from the lateral posterior and lateral dorsal nuclei. Neocortical
      neurons grafted heterotopically into the neocortex of newborn hosts are not only
      able to contact cortical and subcortical targets appropriate for their embryonic
      site of origin, but are also susceptible to derive thalamic inputs closely
      related to their embryonic origin.

PMID- 10077324
TI  - Rabbit P300-like potential depends on cortical muscarinic receptor activation.
AB  - Novel stimuli trigger a positive brain potential P300 or P3a in mammalian
      animals, which is considered to represent an orienting response. Drugs
      systemically administered showed that acetylcholine is involved in the generation
      of P3. However, it is not known in which structure acetylcholine interacts with
      other neuronal substances for P3 generation. In this study, we injected
      scopolamine, an acetylcholine antagonist, into the parietal cortex. After the
      injection the amplitude of P3 from the parietal electrode decreased, while P3
      recorded from neighbouring cortex was preserved. The peak latency of it did not
      show any significant change after the injection. P3 did not show any significant
      change after injecting normal saline into the same area. The parietal cortex is
      an essential structure for local P3 generation Different cerebral cortical
      regions respond to novel stimuli in parallel, and muscarinic receptor activation
      is necessary for processing the information of novelty detection.

PMID- 10077325
TI  - Dehydroepiandrosterone antagonizes the neurotoxic effects of corticosterone and
      translocation of stress-activated protein kinase 3 in hippocampal primary
      cultures.
AB  - Glucocorticoids are toxic to hippocampal neurons. We report here that the steroid
      dehydroepiandrosterone protects neurons of primary hippocampal cultures against
      the toxic effects of corticosterone. Corticosterone (20-500 nM) added for 24h to
      primary cultures of embryonic day 18 rat hippocampus resulted in significant
      neurotoxicity. Dissociated cells were grown for at least 10 days, initially in
      serum-containing medium, but serum was removed before adding steroids for 24 h.
      Neurotoxicity was measured by counting the number of cells stained either for
      beta-tubulin III or glial fibrillary acidic protein. Corticosterone-induced
      toxicity was prevented by co-treatment of the cultures with
      dehydroepiandrosterone (20-500 nM). Dehydroepiandrosterone on its own had little
      effect, though the highest concentration used (500 nM) was mildly toxic.
      Immunohistochemical studies on the nuclear translocation of a range of stress
      activated protein kinases showed that stress-activated protein kinases 1, 2, 3
      and 4 were all translocated by 10 min exposure to corticosterone (100 nM).
      Dehydroepiandrosterone (100 nM) attenuated the translocation of stress-activated
      protein kinase 3, but not the others. These experiments show that
      dehydroepiandrosterone has potent anti-glucocorticoid actions on the brain, and
      can protect hippocampal neurons from glucocorticoid-induced neurotoxicity. This
      protective action may involve stress-activated protein kinase 3-related
      intracellular pathways, though direct evidence for this has still to be obtained.

PMID- 10077326
TI  - Persistent phosphorylation of cyclic AMP responsive element-binding protein and
      activating transcription factor-2 transcription factors following transient
      cerebral ischemia in rat brain.
AB  - The transcription factors cyclic AMP responsive element-binding protein (CREB)
      and activating transcription factor-2 were studied in rat brains subjected to 15
      min ischemia followed by varied periods of reperfusion using western blot and
      immunocytochemical analyses. The total amounts of both CREB and activating
      transcription factor-2 were not altered in the hippocampus after ischemia. In
      contrast, levels of the phosphorylated forms of both transcription factors
      decreased during ischemia but rebounded following reperfusion. The phospho-forms
      of CREB and activating transcription factor-2 showed regional and temporal
      differences in their expression. Phospho-CREB was increased relative to control
      levels at 30 min, and continued to increase for at least three days postischemia,
      mainly in dentate granule cells. The level of phospho-activating transcription
      factor-2 appeared to be higher in CAI pyramidal cells than in dentate granule
      cells after ischemia. The present findings suggest that the signaling pathways
      for phosphorylation of CREB may be neuroprotective for dentate cells, which are
      relatively resistant to ischemic insults. The increased phospho-activating
      transcription factor-2 may reflect increased stresses in these neurons. The more
      modest activation of CREB pathways in CA1 neurons may not be enough to overcome
      the increased stresses in these neurons, contributing to delayed neuronal death.

PMID- 10077327
TI  - Rapid preconditioning neuroprotection following anoxia in hippocampal slices:
      role of the K+ ATP channel and protein kinase C.
AB  - Sublethal cerebral anoxic/ischemic insults may "precondition" and thereby protect
      brain from subsequent anoxic/ischemic insults. We tested two hypotheses in
      hippocampal slices: (i) that short periods of anoxia, each followed by
      reoxygenation, precondition and thereby improve recovery of synaptic activity
      following "lethal" anoxic insults; and (ii) that the ATP-sensitive potassium
      channel [K+ ATP] or protein kinase C mediates anoxic preconditioning
      neuroprotection in hippocampal slices. Hippocampal slices were subjected to three
      short periods of anoxia, each separated by 10 min of reoxygenation. These anoxic
      insults were prolonged only until the onset of anoxic depolarization. Thirty
      minutes following these insults, slices underwent a "test" anoxic insult, which
      was characterized by an anoxic insult that lasted 1 min of anoxic depolarization.
      Recovery of evoked potential amplitudes was followed for 30 min of reoxygenation.
      The beneficial effects of preconditioning was shown by the significant recovery
      of evoked potentials after "test" anoxic insults in preconditioned slices, when
      compared to controls that only underwent a "test" anoxic insult. In control
      slices, transient superfusion with an ATP-sensitive potassium channel agonist (10
      microM pinacidil) 30 min prior to "test" anoxia markedly improved evoked
      potential recovery. Administration of 5 microM of the sulfonylurea tolbutamide,
      an ATP-sensitive potassium channel antagonist during preconditioning insults,
      blocked the protection afforded by preconditioning. Transient superfusion of a
      protein kinase C activator (500 nM phorbol 12-myristate 13-acetate) did not
      improve evoked potential recovery. Administration of 50 nM chelerythrine, a
      protein kinase C inhibitor during preconditioning insults did not block the
      protection afforded by preconditioning. These data support the hypothesis that
      the ATP-sensitive potassium channel is involved in the neuroprotection afforded
      by anoxic preconditioning in hippocampal slices. However, protein kinase C
      activation does not appear to play a role in this neuroprotection.

PMID- 10077328
TI  - Immunohistochemical and neurochemical studies on nigral and striatal functions in
      the circling (ci) rat, a genetic animal model with spontaneous rotational
      behavior.
AB  - Asymmetrical spontaneous turning behavior or circling phenomena are often related
      to components of the dopaminergic system, particularly to an imbalance of
      nigrostriatal function. When a rotational preference is observed, it is typically
      in a direction away from the brain hemisphere with higher striatal dopaminergic
      transmission. We have recently described a rat mutant (ci) with spontaneous
      circling behavior and other signs of functional brain asymmetry. Neurochemical
      determinations showed that mutants of both genders have significantly lower
      concentrations of dopamine and dopamine metabolites in the striatum ipsilateral
      to the preferred direction of rotation. In the present study, we used
      immunohistochemical, neurochemical, and autoradiographic techniques to
      characterize the dopaminergic abnormalities of the ci rat mutant in more detail.
      Age-matched non-affected controls of the same strain were used for comparison.
      Immunohistochemical labeling of dopaminergic neurons and fibers in substantia
      nigra pars compacta, ventral tegmental area, and striatum did not indicate any
      significant neurodegeneration or asymmetry that could explain the lateralization
      in dopamine levels in striatum of ci rats. Neurochemical determinations
      substantiated that ci rats of both genders have a significant imbalance in
      striatal dopamine metabolism, but a similar significant lateralization was also
      seen in non-affected female controls. Comparison of dopamine, serotonin,
      noradrenaline and several monoamine metabolite levels in substantia nigra,
      striatum, nucleus accumbens and frontal cortex of ci rats and controls did not
      disclose any marked difference between affected and non-affected animals which
      was consistently found in both genders. Quantitative autoradiographic
      determination of binding densities of dopamine transporter and D1 and D2
      receptors in several parts of the striatum and substantia nigra indicated that ci
      rats have a significantly higher binding density of dopamine transporter and
      receptors than controls. Taken together, ci mutant rats of both genders exhibit
      an asymmetry in striatal dopamine and metabolite levels and an enhanced dopamine
      transporter and receptor binding, but the link of these differences in
      dopaminergic parameters with the rotational behavior of the animals is not clear
      yet. The lack of any significant dopaminergic cell loss in the substantia nigra
      and the locomotor hyperactivity observed in the mutants clearly suggest that the
      ci rat is not suited as a model of Parkinsonism but rather constitutes a model of
      a hyperkinetic motor syndrome.

PMID- 10077329
TI  - On the distribution patterns of D1, D2, tyrosine hydroxylase and dopamine
      transporter immunoreactivities in the ventral striatum of the rat.
AB  - The distribution of dopamine D1 and D2 receptor immunoreactivities in the nucleus
      accumbens and the olfactory tubercle of adult and postnatal male rats were
      compared with the distribution of tyrosine hydroxylase and dopamine transporter
      immunoreactivities. An overall co-distribution of D1 and D2 receptor
      immunoreactivities with tyrosine hydroxylase immunoreactivity was found in the
      nucleus accumbens and the olfactory tubercle. However, the major finding in this
      study was, following a more detailed analysis in coronal sections of the shell
      part of the nucleus accumbens, the existence of nerve cell patches of strong D1
      receptor immunoreactivity associated with low D2 receptor, dopamine transporter
      and tyrosine hydroxylase immunoreactivities. These patches were mainly surrounded
      by areas of strong D2 receptor, tyrosine hydroxylase and dopamine transporter
      immunoreactivities and could be found also in the olfactory tubercle. Similar
      observations were made in postnatal rats. Serial reconstructions of the patches
      of strong D1 receptor immunoreactivity in the rostrocaudal direction were made.
      The patches formed a continuous tubular nerve cell system in the shell part of
      the nucleus accumbens. Since this nerve cell system was found to be surrounded by
      a high density of dopamine terminals, it may represent a compartment where
      dopamine transmission mainly acts on D1 receptors via local diffusion (i.e. via
      volume transmission). However, it must be noted that the D1 receptor rich patches
      constitute only a small fraction of the nucleus accumbens and the overall density
      of tyrosine hydroxylase immunoreactive terminals correlates with the density of
      both D1 and D2 receptors in the nucleus accumbens. In conclusion, the present
      paper gives new aspects on the chemical microarchitecture of the nucleus
      accumbens.

PMID- 10077330
TI  - Local infusion of the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione does
      not block D1 dopamine receptor-mediated increases in immediate early gene
      expression in the dopamine-depleted striatum.
AB  - Administration of selective agonists of D1 dopamine receptors increases immediate
      early gene expression in striatal neurons, a response which is particularly
      robust in the dopamine-depleted striatum. Although interactions between dopamine
      and glutamate receptor-mediated responses in striatal neurons have been
      demonstrated in a number of experimental paradigms, our previous findings
      indicate that N-methyl-D-aspartate antagonists do not block D1 receptor-mediated
      induction of immediate early genes in the dopamine-depleted striatum. In the
      present study, we therefore examined interactions between D1 dopamine receptors
      and the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate
      subtypes of glutamate receptor by determining whether striatal infusion of the
      (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione would block D1 receptor-mediated induction of
      the immediate early genes c-fos and zif268 in the dopamine-depleted striatum.
      Striatal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (1 mM) completely
      blocked (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate-induced c-fos
      and zif268 expression. However, 6-cyano-7-nitroquinoxaline-2,3-dione (1 microM-1
      mM) did not significantly affect induction of c-fos and zif268 by D1 receptor
      stimulation (SKF 38393, 2 mg/kg, i.p.) in the dopamine-depleted striatum. To more
      generally block excitatory input, tetrodotoxin (10 microM) was infused into the
      striatum of rats receiving a D1 agonist. Local infusion of tetrodotoxin had
      minimal effect on induction of c-fos and zif268 in the dopamine-depleted
      striatum. In contrast, tetrodotoxin abolished induction of c-fos and zif268
      messenger RNAs by the D2 antagonist eticlopride (0.5 mg/kg, i.p.) in both intact
      rats and dopamine-depleted rats receiving continuous D2 agonist treatment
      (quinpirole, 0.5 mg/kg/day). The results indicate that D1 receptor-mediated
      induction of immediate early genes in the dopamine-depleted striatum occurs by
      mechanisms that are independent of excitatory input through (+/-)-alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate/kainate receptors.

PMID- 10077331
TI  - Compartmental expression of trkB receptor protein in the developing striatum.
AB  - To investigate the role of neurotrophins in the initial formation of striatal
      patch versus matrix, the spatial and temporal expression of trkB receptors was
      examined using immunohistochemistry. Polyclonal antibodies, against the C
      terminus or the tyrosine kinase domain, revealed trkB-immunoreactive cells and
      fibers localized to patches beginning on embryonic day 19 in the rat, which co
      localized with patchy dopamine fibers, substance P-immunoreactive neurons and
      glutamate receptors. Patchy striatal trkB expression was maintained after
      lesioning the nigrostriatal dopamine system. The patchy trkB distribution
      persisted through postnatal day 14, then became more homogeneous at the same time
      that nigrostriatal afferents become homogeneous. Later in development, trkB
      immunoreactivity was most intense in a subpopulation of large striatal cells that
      were similar in size and frequency to those immunoreactive for choline
      acetyltransferase. The spatiotemporal expression of trkB receptor in
      phenotypically distinct striatal patches, as well as evidence that neurotrophins
      regulate expression of neuronal phenotypic markers during development, may
      indicate a convergence of neurotrophins and afferent innervation on to future
      patch cells that may regulate the establishment of striatal compartmentalization.

PMID- 10077332
TI  - The influence of salt loading on vasopressin gene expression in magno- and
      parvocellular hypothalamic neurons: an immunocytochemical and in situ
      hybridization analysis.
AB  - Arginine vasopressin peptide and messenger RNA expression were examined at the
      cellular level in the magnocellular and parvocellular neurons in the rat
      paraventricular nucleus after dehydration and rehydration, employing
      immunocytochemistry and in situ hybridization histochemistry on the same tissue
      sections. Most magnocellular vasopressinergic neurons of control animals
      expressed both vasopressin-like immunoreactivity and messenger RNA. However,
      neurons negative for vasopressin-like immunoreactivity but expressing messenger
      RNA were also detected, and their number increased during dehydration. In
      contrast, almost all of the parvocellular vasopressinergic neurons of dehydrated
      animals expressed vasopressin messenger RNA alone, with continued increase in
      their number after rehydration, despite return of the number of magnocellular
      vasopressinergic neurons to the control level. Vasopressin messenger RNA and
      corticotropin releasing factor-like immunoreactivity were co-localized in the
      same parvocellular neurons, and vasopressin-immunoreactive nerve terminals were
      detected in the external zone of the median eminence. These findings suggest that
      magno- and parvocellular vasopressinergic neurons are differentially activated
      during dehydration/rehydration. Osmotic stimuli activate all magnocellular
      vasopressinergic neurons, but the effect is not simultaneous in all of these
      neurons. Parvocellular vasopressinergic neurons are also activated by the stress
      of dehydration which effect appears to last longer than in the magnocellular
      system.

PMID- 10077333
TI  - Intrathecal substance P-induced thermal hyperalgesia and spinal release of
      prostaglandin E2 and amino acids.
AB  - Substance P is an important neuromediator in spinal synaptic transmission,
      particularly in processing nociceptive afferent information. The effects of
      substance P are mediated by activation of the neurokinin 1 receptor. Evidence has
      suggested that excitatory amino acids such as glutamate, and prostaglandins
      including prostaglandin E2 are involved in the enhanced spinal excitability and
      hyperalgesia produced by spinal substance P. In the present study, we have
      demonstrated that intrathecal injection of substance P (20 nmol) in rats
      chronically implanted with intrathecal dialysis catheters induced a decrease in
      thermal paw withdrawal latency (before: 10.4+/-0.3 s; after 7.6+/-0.6 s), which
      was accompanied by an increase in prostaglandin E2 (362+/-37% of baseline),
      glutamate (267+/-84%) and taurine (279+/-57%), but not glycine, glutamine, serine
      or asparagine. Intrathecal injection of artificial cerebrospinal fluid had no
      effect upon the behavior or release. Substance P-induced thermal hyperalgesia and
      prostaglandin E2 release were significantly attenuated by a selective neurokinin
      1 receptor antagonist RP67580, but not by an enantiomer RP68651. However,
      substance P-induced release of glutamate and taurine was not reduced by treatment
      with RP67580. SR140333, another neurokinin 1 receptor antagonist, displayed the
      same effects as RP67580 (i.e. block of thermal hyperalgesia and prostaglandin E2
      release, but not release of amino acids). These results provide direct evidence
      suggesting that the spinal substance P-induced thermal hyperalgesia is mediated
      by an increase in spinal prostaglandin E2 via activation of the neurokinin 1
      receptor. These findings define an important linkage between small afferents,
      sensory neurotransmitter release and spinal prostanoids in the cascade of
      spinally-mediated hyperalgesia. The evoked release of glutamate is apparently not
      a result of activation of neurokinin 1 receptors. Accordingly, consistent with
      other pharmacological data, acute spinal glutamate release does not contribute to
      the hyperalgesia induced by activation of spinal neurokinin 1 receptors.

PMID- 10077334
TI  - Temporal and spatial relationships between lipopolysaccharide-induced expression
      of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain.
AB  - Interleukin-1beta plays an important role in mediating central components of the
      host response to peripheral infection such as fever and neuroendocrine activation
      by acting in the brain. The present study assessed whether interleukin-1beta
      produced in the brain is relevant to neuronal activation and the fever response
      induced by intraperitoneal injection of bacterial lipopolysaccharide. The
      distributions of Fos protein, interleukin-1beta protein and inducible nitric
      oxide synthase messenger RNA, used as an anatomical indicator of interleukin
      1beta bioactivity, were compared in brains of animals killed 2, 4 or 8 h after
      lipopolysaccharide (250 microg/kg) or saline injection. Saline did not induce
      interleukin-1beta or Fos immunoreactivity in the brain. Interleukin-1beta
      positive cells were found 2 h after lipopolysaccharide injection in
      circumventricular organs. Fos immunoreactivity at this time-point was not found
      in circumventricular organs, but in parenchymal structures such as the nucleus of
      the solitary tract, paraventricular hypothalamus and ventromedial preoptic area.
      Fos expression did occur in circumventricular organs only 8 h after
      lipopolysaccharide injection. This late pattern of Fos expression coincided with
      the rise in body temperature and the induction of inducible nitric oxide synthase
      messenger RNA. These data show that after peripheral lipopolysaccharide
      administration interleukin-1beta is synthesized and bioactive in
      circumventricular organs. Interleukin-1beta may activate local neurons that
      induce fever and neuroendocrine activation via projections to the ventromedial
      preoptic area and the nucleus of the solitary tract.

PMID- 10077335
TI  - Primary cortical glial reaction versus secondary thalamic glial response in the
      excitotoxically injured young brain: microglial/macrophage response and major
      histocompatibility complex class I and II expression.
AB  - The excitatory amino acid analog, N-methyl-D-aspartate, was injected
      intracortically into nine-day-old rats. Resulting axon-sparing lesions in the
      developing sensorimotor cortex, which secondarily affect thalamic neurons that
      become deprived of cortical targets, provide an experimental model for the study
      of the glial response in distantly affected areas. The microglial/macrophage
      response was studied using tomato lectin histochemistry and major
      histocompatibility complex I and II immunocytochemistry. Blood-brain barrier
      integrity was evaluated. In the cortical lesion site, where blood-brain barrier
      breakdown occurs, the rapid microglial response was restricted to the
      degenerating area. Microglial changes were first seen at 4 h post-injection,
      peaking at days 3-5. Reactive microglia changed morphology, increased tomato
      lectin binding and expressed major histocompatibility complex I. Additionally,
      some cells expressed major histocompatibility complex II. In the secondarily
      affected thalamus, the microglial response was not as pronounced as in the
      cortex, was first seen at 10 h post-injection and peaked at days 3-5. Reactive
      microglia showed a bushy morphology, were intensely lectin positive and expressed
      major histocompatibility complex I. The exceptional response of the nine-day-old
      brain to cortical lesions makes this model an interesting tool for studying the
      implications of microglial major histocompatibility factor expression in still
      enigmatic processes such as wound healing and plasticity.

PMID- 10077336
TI  - Aromatase expression by astrocytes after brain injury: implications for local
      estrogen formation in brain repair.
AB  - Recent evidence indicates that 17beta-estradiol may have neuroprotective and
      neuroregenerative properties. Estradiol is formed locally in neural tissue from
      precursor androgens. The expression of aromatase, the enzyme that catalyses the
      conversion of androgens to estrogens, is restricted, under normal circumstances,
      to specific neuronal populations. These neurons are located in brain areas in
      which local estrogen formation may be involved in neuroendocrine control and in
      the modulation of reproductive or sex dimorphic behaviours. In this study the
      distribution of aromatase immunoreactivity has been assessed in the brain of mice
      and rats after a neurotoxic lesion induced by the systemic administration of
      kainic acid. This treatment resulted in the induction of aromatase expression by
      reactive glia in the hippocampus and in other brain areas that are affected by
      kainic acid. The reactive glia were identified as astrocytes by co-localization
      of aromatase with glial fibrillary acidic protein and by ultrastructural
      analysis. No immunoreactive astrocytes were detected in control animals. The same
      result, the de novo induction of aromatase expression in reactive astrocytes on
      the hippocampus, was observed after a penetrating brain injury. Furthermore,
      using a 3H2O assay, aromatase activity was found to increase significantly in the
      injured hippocampus. These findings indicate that although astrocytes do not
      normally express aromatase, the enzyme expression is induced in these glial cells
      by different forms of brain injury. The results suggest a role for local
      astroglial estrogen formation in brain repair.

PMID- 10077337
TI  - Ciliary neurotrophic factor is an axogenesis factor for retinal ganglion cells.
AB  - Although mature mammalian retinal ganglion cells normally fail to regrow injured
      axons, exposure to the molecular environment of the peripheral nervous system
      stimulates regenerative growth. The present study used dissociated rat retinal
      ganglion cells purified by immunopanning to identify peripheral nervous system
      derived factors that promote axonal outgrowth. Of the multiple growth factors
      investigated, only ciliary neurotrophic factor and the related cytokine, leukemia
      inhibitory factor, had striking neuritogenic activity, with half-maximal effects
      at 1-2 ng/ml. Brain-derived neurotrophic factor stimulated retinal ganglion cell
      survival nearly as well as ciliary neurotrophic factor, but had only minor
      effects on outgrowth. Thus, the neuritogenic effects of ciliary neurotrophic
      factor are not a simple consequence of increased survival. Ciliary neurotrophic
      factor-stimulated outgrowth was correlated with increased expression of the
      growth-associated membrane phosphoprotein, GAP-43, a hallmark of optic nerve
      regeneration in vivo. A high molecular weight fraction from media conditioned by
      rat optic or sciatic nerve mimicked the effect of ciliary neurotrophic factor in
      inducing axonal outgrowth. Ciliary neurotrophic factor was detected in the
      conditioned media on western blots, and the biological activity of the
      conditioned media was neutralized with an anti-ciliary neurotrophic factor
      antibody. These results indicate that ciliary neurotrophic factor has specific
      effects on axon outgrowth in retinal ganglion cells that are dissociable from its
      effects on cell survival, and that ciliary neurotrophic factor accounts for most
      of the axon-promoting activity for retinal ganglion cells present in either the
      sciatic or optic nerve.

PMID- 10077338
TI  - Smooth endoplasmic reticulum in fish Mauthner cells at different functional
      states.
AB  - The ultrastructure of Mauthner cells of goldfish fry and adult xenotoca in intact
      state and after prolonged natural stimulation has been studied qualitatively and
      quantitatively. Additionally, Mauthner cells of intact adult goldfish and adult
      rotan Percottus glehni were investigated. In all adult fish the dendroplasm of
      the two major dendrites was shown to contain a regular network of smooth
      endoplasmic reticulum, with cisterns and tubules arranged transversally to the
      dendrite stem. In the Mauthner cells of intact goldfish fry, the reticulum was
      not clearly expressed, the transversal cisterns occurred occasionally. After
      stimulation, however, it became more developed probably due to proliferation of
      additional transversal cisterns. The periodicity of transversally oriented
      cisterns in the dendrites of Mauthner cells in each fish species studied was
      nearly the same. However, the number of transversal cisterns per unit of dendrite
      length, and the total length of cisterns and tubules per unit of cross-section
      area varied both within and among the species. These parameters increased after
      stimulation. It is suggested that the proliferation of the transversal cisterns
      in the endoplasmic reticulum and the extent of their development depend on the
      functional state of the afferent synapses and the plasticity of the smooth
      reticulum reflects the involvement of postsynaptic mechanisms in regulation of
      Mauthner cell stability presumably via the regulation of calcium homeostasis
      under varying conditions of functioning.

PMID- 10077339
TI  - Potassium channels of myenteric neurons in guinea-pig small intestine.
AB  - Patch-clamp recording was used to study rectifying K+ currents in myenteric
      neurons in short-term culture. In conditions that suppressed Ca2+ -activated K+
      current, three kinds of voltage-activated K+ currents were identified by their
      voltage range of activation, inactivation, kinetics and pharmacology. These were
      A-type current, delayed outwardly rectifying current (I(K),dr) and inwardly
      rectifying current (I(K),ir). I(K),ir consisted of an instantaneous component
      followed by a time-dependent current that rapidly increased at potentials
      negative to -80 mV. Time-constant of activation was voltage-dependent with an e
      fold decrease for a 31-mV hyperpolarization amounting to a decrease from 800 to
      145 ms between -80 and -100 mV. I(K),ir did not inactivate. I(K),ir was abolished
      in K+ -free solution. Increases in external K+ increased I(K),ir conductance in
      direct relation to the square root of external K+ concentration. Activation
      kinetics were accelerated and the activation range shifted to more positive K+
      equilibrium potentials. I(K),ir was suppressed by external Cs+ and Ba2+ in a
      concentration-dependent manner. Ca2+ and Mg+ were less effective than Ba2+.
      I(K),ir was unaffected by tetraethylammonium ions. I(K),dr was activated at
      membrane potentials positive to - 30 mV with an e-fold decrease in time-constant
      of activation from 145 to 16 ms between -20 and 30 mV. It was half-activated at 5
      mV and fully activated at 50 mV. Inactivation was indiscernible during 2.5 s test
      pulses. I(K),dr was suppressed in a concentration-, but not voltage-dependent
      manner by either tetraethylammonium or 4-aminopyridine and was insensitive to
      Cs+. The results suggest that I(K),ir may be important in maintaining the high
      resting membrane potentials found in afterhyperpolarization-type enteric neurons.
      They also suggest importance of I(K),ir channels in augmentation of the large
      hyperpolarizing after-potentials in afterhyperpolarization-type neurons and the
      hyperpolarization associated with inhibitory postsynaptic potentials. I(K),dr in
      afterhyperpolarization-type enteric neurons has overall kinetics and voltage
      behaviour like delayed rectifier currents in other excitable cells where the
      currents can also be distinguished from A-type and Ca2+ -activated K+ current.

PMID- 10077340
TI  - Troglitazone exhibits immunomodulatory activity on the cytokine production of
      activated human lymphocytes.
AB  - Troglitazone (TGL), a thiazolidinedione compound that improves the response of
      peripheral target tissue to insulin, also has anti-inflammatory properties, a
      potential means of protection from Type 1 (insulin dependent) diabetes. In order
      to test the ability of TGL to affect cytokine production, peripheral blood
      mononuclear cells from healthy donors were exposed to TGL in the presence or
      absence of a polyclonal activator (PHA) and the production of cytokines assayed.
      TGL enhanced PHA response, promoted secretion of the cytokines granulocyte and
      macrophage colony-stimulating factor and leukaemia inhibitory factor and
      inhibited tumour necrosis factor-alpha secretion, consistent with causing Th-2
      differentiation in T-cells. These results suggest that TGL is capable of
      modulating cytokine production and could therefore influence Th1/Th2
      differentiation.

PMID- 10077341
TI  - Decreased Na,K-ATPase activity by glycation at the catalytic center.
AB  - The in vitro activity of Na,K-ATPase isolated from outer medulla of dog kidney
      was decreased in a dose- and time-dependent manner by interaction with 100 mM
      glucose 6-phosphate (G6P) during the first 8 h. In the subsequent 16 h no change
      in activity was observed. On the other hand, Amadori-products of the enzyme
      increased in a dose- and time-dependent manner by glycation up to 100 mM G6P
      during 24 h. The presence of 5 mM ATP in glycation experiments protected the
      enzyme activity but did not inhibit the formation of Amadori-products. These
      results were consistent with inhibition of the Na,K-ATPase activity by glycation
      of the amino groups located in the catalytic center of the molecule.

PMID- 10077342
TI  - Effect of epidermal growth factor on enzymes of phospholipid biosynthesis in lung
      and liver of fetal rat in vivo and in vitro.
AB  - Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface
      receptors, is an important regulator of cell differentiation and fetal lung
      surfactant synthesis, and may be used as a potential novel therapeutic agent in
      prematurity. Nevertheless, the distinct role in lung development and its
      mechanisms of action are not well understood. We investigated in vivo the
      systemic effect of intrafetally administered EGF (200 ng/g fetal body weight) and
      maternally administered dexamethasone (DEXA; 0.2 and 2.0mg/kg maternal body
      weight) on the activity of important enzymes of the phospholipid synthesis in the
      fetal rat lung and liver: choline kinase (EC 2.7.1.32), cholinephosphate
      cytidyltransferase (EC 2.7.7.15), choline phosphotransferase (EC 2.7.8.2),
      lysolecithin acyltransferase (EC 2.3.1.23) and glycerolphosphate
      phosphatidyltransferase (EC 2.7.8.5). Additionally, in vivo and in vitro effects
      of DEXA on EGF receptor synthesis, and the effects of EGF on protein content and
      morphogenesis of the fetal rat lung organoid culture, were evaluated. Whereas
      DEXA induced the activity of all investigated enzymes of phospholipid synthesis
      and increased EGF receptor synthesis, EGF has no effects on the enzymes, either
      in vivo or in vitro. EGF enhanced protein synthesis and morphogenesis in vitro.
      With respect to our data and the literature, we hypothesize that DEXA and EGF may
      act on different cellular sides. Whereas glucocorticoids induce surfactant
      phospholipid synthesis, EGF should be more involved in cell proliferation and
      morphogenesis.

PMID- 10077343
TI  - Serum interleukin-6 in renal osteodystrophy: relationship with serum PTH and bone
      remodeling markers.
AB  - Interleukin-6, synthesized by osteoblasts in response to PTH, stimulates
      osteoclastogenesis and bone resorption in vitro, and it has been implicated in
      the pathogenesis of bone loss in several clinical situations. The aim of this
      study was to evaluate whether serum levels of interleukin-6 were increased in
      patients with renal osteodystrophy, and to investigate the possible relationships
      between serum interleukin-6 and PTH levels on one hand, and serum interleukin-6
      and bone remodeling markers on the other. Serum interleukin-6 (IL-6), intact PTH,
      osteocalcin, bone alkaline phosphatase (BAP) and carboxyterminal telopeptide of
      Type 1 collagen (ICTP) were measured in 86 uremic patients. IL-6 (median [range]
      16.5 [1.0-430] pg/ml), PTH (279.8 [11-2004] pg/ml), osteocalcin (143.8 [8-921]
      ng/ml), BAP (20.9 [6-169] U/I) and ICTP (38.8 [1.5-181.5] microg/l) were higher
      than normal. IL-6 levels correlated with PTH (r= 0.22, p = 0.04) and with ICTP (r
      = 0.31, p = 0.004). A stronger correlation was found between PTH and circulating
      bone remodeling markers (r = 0.66 for osteocalcin, r = 0.56 for BAP, and r = 0.39
      for ICTP). The correlation between PTH and IL-6 was stronger in those patients (n
      = 15) with severe secondary hyperparathyroidism (r= 0,71, p = 0.003). On the
      other hand, in the group of patients (n = 41) with PTH lower than 250 pg/ml,
      there was no correlation between IL-6 and PTH, while IL-6 correlated with ICTP (r
      = 0.44, p = 0.006). Serum IL-6 correlates with ICTP which suggests that it may
      mediate bone resorption in renal osteodystrophy.

PMID- 10077344
TI  - Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic
      fatigue syndrome.
AB  - Previous studies have demonstrated concentrating neuroendocrinological
      disturbances in chronic fatigue syndrome (CFS) patients, concentrating in
      particular on low cortisol levels and a hypothalamic deficiency. In order to
      investigate the dynamic response of the adrenal glands, we measured
      dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH)
      stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls. We
      found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v.
      ACTH injection. This observation adds to the large amount of evidence of
      endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might
      contribute to the overall clinical picture in CFS, and could explain some of the
      immunological disturbances observed in this syndrome.

PMID- 10077345
TI  - Effects of human growth hormone on the porto-arterial concentration differences
      of glucose and amino acids in the newborn piglet.
AB  - It is known that growth hormone (GH) increases the mitotic index of duodenal
      crypt cells. In early life, such an effect could be of particular importance for
      the functional development of the intestine in terms of absorptive capacity. In
      this study, osmotic mini pumps were introduced into the abdominal cavity of
      newborn piglets. The pumps permitted a continuous infusion of either recombinant
      human growth hormone (rhGH) at a rate of 0.1 IU GH x kg(-1) x 24 h(-1) or of
      vehicle. After 7 days of treatment, a bolus of amino acids and glucose was
      infused into the duodenum. Following this bolus, there was a prompt rise in the
      plasma concentration of both amino acids and glucose, especially in blood
      withdrawn from the portal vein. Thus, when the differences in concentrations of
      both amino acids and glucose between portal and arterial blood plasma were
      calculated, these differences reached maximum values between 30 and 60 minutes
      after the bolus. In animals treated with GH, maximum values occurred at a lower
      level than in control animals. These reductions were in the order of 60% (P >
      0.01) if calculated over the first hour of absorption. From this study, it might
      be concluded that GH does not improve the absorptive capacity of the small
      intestine in newborn piglets. Instead, GH seems to reduce the absorption dynamics
      of glucose and amino acids. The reason for this is obscure, but could imply a
      specific effect of GH on enterocyte function.

PMID- 10077346
TI  - Study of tobacco smoke influence on content of estrogens and DNA flow cytometry
      data in uterine tissue of rats of different age.
AB  - Female rats aged 2.5-3 months ("young") and 6 months ("adult") were or were not
      exposed to the influence of tobacco smoke (mainstream cigarette smoke, 2 hrs/day
      during 3 weeks or 3 months). Treatment with tobacco smoke did not induce any
      changes in uterine weight or estrous cycle but led to the decrease of estradiol
      (E2) concentration in uterine tissue (especially in adult rats or in young rats
      after 3 months of experiment). No signs of aneuploidy were found in uteruses of
      animals-"smokers" though proliferation index and percentage of cells in S-phase
      were increased (according to flow cytometry data) by 3 weeks and decreased by 3
      months of experiment. The data obtained support previously made assumption
      pointing to phasic character of changes in reproductive system under the
      influence of tobacco smoke and may be used for further confirmation of the
      concept explaining the role of smoking in the shift of hormonal (estrogen
      induced) carcinogenesis type from promotional to genotoxic one.

PMID- 10077347
TI  - Immobilization-dependent bone collagen breakdown appears to increase with time:
      evidence for a lack of new bone equilibrium in response to reduced load during
      prolonged bed rest.
AB  - The purpose of this study was to evaluate the effect of prolonged immobilization
      on bone, in order to investigate how skeletal turnover adapts to bed rest. We
      examined indices of bone formation and bone resorption in the serum and urine of
      fifty-four patients (26 males and 28 females) immobilized after an episode of
      paralytic stroke. The length of immobilization ranged from 30 to 180 days. A
      significant, time-dependent increase in markers of resorption - urinary
      pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), serum Type I collagen cross
      linked C-telopeptide (ICTP) - was observed in immobilized patients, as compared
      to free-living healthy subjects. The positive correlation between resorption
      markers increase and the length of immobilization suggests that the rate of bone
      resorption did not decrease with time. On the other hand, the levels of markers
      of bone formation - bone-specific alkaline phosphatase (B-ALP), and the carboxyl
      terminal propeptide of Type I procollagen (PICP) - remained within the normal
      range in all patients, regardless the length of immobilization. Our results would
      indicate an uncoupling between bone formation and bone resorption during bed
      rest, and suggest that the bone collagen break-down was not a self-limiting
      process in immobilized patients, and that a new equilibrium or "steady state" in
      response to the reduced load was not reached in the skeleton.

PMID- 10077348
TI  - Serum leptin concentrations during short-term administration of growth hormone
      and triiodothyronine in healthy adults: a randomised, double-blind placebo
      controlled study.
AB  - The regulation of adipose tissue mass and energy expenditure is currently subject
      to intensive research, which primarily relates to the discovery of leptin. Leptin
      is a peptide, which is the product of the obese (ob) gene expressed in adipose
      tissue of several species icluding humans. Leptin is supposed to serve both as an
      index of fat mass and as a sensor of energy balance. Administration of
      recombinant murine leptin in ob/ob-mice, which do not produce leptin, decreases
      food intake and increases thermogenesis both of which result in a reduction in
      body weight and adipose tissue mass. The calorigenic effect of leptin presumably
      acts through an increase in sympathetic outflow which in turn activates the beta3
      adrenergic receptor in brown adipose tissue. The regulation and action of
      endogenous leptin in humans are less well understood, and clinical grade
      recombinant human leptin is so far not available. Serum leptin correlates
      logarithmically with total body fat in both normal weight and obese subjects,
      which suggest insensitivity to leptin in obese patients. Furthermore, more rapid
      excursions in serum leptin have been reported following short-term changes in
      caloric intake and administration of insulin. Growth hormone (GH) exerts
      pronounced effects on lipid metabolism and resting energy expenditure. The
      lipolytic actions of GH appear to involve both increased sensitivity to the beta
      adrenergic pathway, and a suppression of adipose tissue lipoprotein lipase
      activity. The calorigenic effects of GH have been shown not only to be secondary
      to changes in lean body mass. Growth hormone administration furthermore increases
      the peripheral conversion of thyroxine to triiodothyronine, which may contribute
      to the overall actions of GH on fuel and energy metabolism. So far, little is
      known about the effects of GH and iodothyronines on serum leptin levels in
      humans. We therefore measured serum leptin levels and energy expenditure before
      and after the administration of GH and triiodothyronine, alone and in combinaion,
      in a randomized double-blind placebo-controlled study in healthy young male
      adults. The dose of triiodothyronine was selected to obtain serum levels
      comparable to those seen after GH administration.

PMID- 10077349
TI  - Molecular aspects of mammalian ovulation.
AB  - Ovulation, recurring every reproductive cycle of the mammalian female and
      triggered by a surge of luteinizing hormone (LH) released from the pituitary is
      an essential prerequisite for fertilization and subsequent embryonic development.
      Here we shall review two of the biological responses leading to follicle rupture 
      - vascular changes and proteolysis. Naturally, our present knowledge is based
      mainly on work in a few species, such as the rat, the mouse and, to lesser extent
      the pig and monkeys and observations in the human. Therefore any generalizations
      to other mammals, should be considered as a working hypothesis yet to be
      confirmed. The LH surge stimulates, in the preovulatory follicles, a cascade of
      proteolytic enzymes, including plasminogen activator (PA), plasmin and matrix
      metalloproteinases (MMPs). These enzymes bring about the degradation of
      perifollicular matrix and, most notably, the decomposition of the meshwork of
      collagen fibers which provides the strength to follicular wall. Pharmacological
      blockage of any of these enzymes resulted in the reduction of ovulation rate. The
      increased ovarian proteolytic activity associated with ovulation is controlled by
      locally produced specific inhibitors, plasminogen activator inhibitor-1 (PAI-1)
      and tissue inhibitor of metalloproteases-1 (TIMP-1). The increased synthesis of
      these two specific proteinase inhibitors in the theca of growing follicles
      ensures their development by protecting them from enzymes diffusing from
      ovulatory follicles. The stimulation of ovulation by the gonadotropin results in
      an increase in follicular blood flow, hyperemia, increase in vascular
      permeability and a marked increase in follicular volume. These vascular changes
      and the proteolytic activity are triggered either directly by LH or by local
      mediators and factors produced in response to the gonadotropic stimulus. These
      mediators allow the tight coordination of these two cascades culminating in the
      rupture of follicle wall. We shall review here, briefly, the various mediatory
      systems that have been implicated in follicle rupture. These include steroids,
      vascular endothelial growth factor (VEGF), cytokines, eicosanoids, platelet
      activating factor (PAF), nitric oxide and nitric oxide synthase (NO/NOS), kinins
      and oxygen radicals.

PMID- 10077350
TI  - Drinking water fluoridation and bone.
AB  - Drinking water fluoridation has an established role in the prevention of dental
      caries, but may also positively or negatively affect bone. In bone fluoride is
      incorporated into hydroxylapatite to form the less soluble fluoroapatite. In
      higher concentrations fluoride stimulates osteoblast activity leading to an
      increase in cancellous bone mass. As optimal drinking water fluoridation (1 mg/l)
      is widely used, it is of great interest, whether long-term exposition to
      artificial water fluoridation has any impact on bone strength, bone mass, and --
      most importantly -- fracture rate. Animal studies suggest a biphasic pattern of
      the effect of drinking water fluoridation on bone strength with a peak strength
      at a bone fluoride content of 1200 ppm followed by a decline at higher
      concentrations eventually leading to impaired bone quality. These changes are not
      paralleled by changes in bone mass suggesting that fluoride concentrations remain
      below the threshold level required for activation of osteoblast activity.
      Accordingly, in most epidemiological studies in humans bone mass was not altered
      by optimal drinking water fluoridation. In contrast, studies on the effect on hip
      fracture rate gave conflicting results ranging from an increased fracture
      incidence to no effect, and to a decreased fracture rate. As only ecological
      studies have been performed, they may be biased by unknown confounding factors --
      the so-called ecological fallacy. However, the combined results of these studies
      indicate that any increase or decrease in fracture rate is likely to be small. It
      has been calculated that appropriately designed cohort studies to solve the
      problem require a sample size of >400,000 subjects. Such studies will not be
      performed in the foreseeable future. Future investigations in humans should,
      therefore, concentrate on the effect of long-term drinking water fluoridation on
      bone fluoride content and bone strength.

PMID- 10077351
TI  - Deficient activation and different expression of transforming growth factor-beta
      isoforms in active proliferative diabetic retinopathy and neovascular eye
      disease.
AB  - An increased expression and secretion of angiogenic growth factors was proposed
      to occur in proliferative diabetic retinopathy and other neovascularizing retinal
      diseases. However, a loss of anti-angiogenic factors also might promote retinal
      neovascularization. Therefore we investigated the active and latent vitreous
      levels of the subtypes of the endothelial anti-mitogen transforming growth factor
      beta in vitreous of 58 patients. Four groups of patients were compared: Controls
      without retinal hypoxia, patients with quiescent and active proliferative
      diabetic retinopathy (PDR), and patients with severe retinal hypoxia resulting in
      rubeosis iridis. Whereas the amount of total TGF-beta in the four groups did not
      differ significantly, latent TGF-beta isoform expression showed complex
      alterations in ocular vitreous. Levels of active TGF-beta of patients with active
      PDR (79.5 +/- 28 pg/ml; n = 8) were decreased to 20% of the control levels (378
      +/- 55 pg/ml; n = 12; p = 0.0005) and 25% of the mean concentration in quiescent
      PDR (346 +/- 64 pg/ml; n = 9; p = 0.0021). Levels in rubeosis (52 +/- 10 pg/ml; n
      = 10) did not differ significantly from those found in active PDR but were
      decreased to 15% of those in patients with quiescent PDR (p = 0.0004).
      Furthermore a highly significant inverse correlation between active TGF-beta and
      alpha2-antiplasmin, a liver produced inhibitor of the activation of TGF-beta by
      plasmin was noted (r = -0.59; n = 28; p = 0.001). We conclude that deficient
      activation of TGF-beta occurs in active proliferative diabetic retinopathy and in
      hypoxic angiogenesis most likely as a consequence of a blood retina barrier
      breakdown and influx of alpha2-antiplasmin from serum. The disinhibition of
      endothelial cell proliferation may be a central component in the process of
      neovascularization.

PMID- 10077352
TI  - Phosphatase inhibitors induce defective hormone secretion in insulin-secreting
      cells and entry into apoptosis.
AB  - A long-term (> or =24 h) exposure of insulin-secreting HIT T15 cells to the
      phosphatase inhibitor, okadaic acid (OA), at concentrations inhibiting
      serine/threonine phosphatases 1 (PP1) and 2A (PP2A) reduced proliferation and
      insulin secretion. The reduced proliferation was related to the induction of
      apoptosis as evidenced by morphological criteria and the occurrence of
      internucleosomal DNA fragmentation after 15 h in 50 nM OA. The compromised
      insulin secretion was not simply a consequence of a lowered hormone content and
      cell growth, but comprised also a complete suppression of secretion stimulated by
      K+ depolarisation and forskolin. K+ depolarisation of HIT cells cultured for 24 h
      in 50 nM OA resulted in a nearly unimpaired influx of Ca2+, but did not induce
      secretion. These observations suggest that the secretory defect may be localised
      distal to Ca2+ influx in stimulus secretion coupling of insulin-secreting cells.

PMID- 10077353
TI  - Enhanced erythrocyte aggregation in type 2 diabetes with late complications.
AB  - We investigated whether erythrocyte aggregation (EA) is enhanced in type 2
      diabetic patients who have developed microvascular or macrovascular
      complications. EA rates at high and low shear rates were analysed in 141 patients
      with type 2 diabetes who were further divided into 4 subgroups according to the
      status of diabetic complications and degree of metabolic control. Groups 1 (n =
      43) and 2 (n = 23) consisted of well-controlled patients without and with
      clinically evident late complications, while groups 3 (n = 33) and 4 (n = 42)
      represented poorly controlled patients without and with these complications,
      respectively. 124 healthy subjects served as the control group. Mean EA rate was
      comparable between control subjects and group 1 both at high (2.05 +/- 0.03 vs.
      2.14 +/- 0.07, respectively) and low (6.96 +/- 0.02 vs. 7.04 +/- 0.06,
      respectively) shear rates. Mean EA rate was also comparable between groups 2 and
      4 at high (2.76 +/- 0.09 vs. 2.94 +/- 0.07, respectively) and low (8.18 +/- 0.13
      vs. 8.41 +/- 0.1, respectively) shear rates. However, EA at both shear rates in
      groups 2 and 4 were significantly higher than control subjects, group 1 (p <
      0.0001) and group 3 (high shear rate EA: 2.76 +/- 0.09 and low shear rate EA:
      7.48 +/- 0.07 (p < 0.01). In group 3, EA rates were significantly higher than
      control subjects and group 1 (p < 0.05) at both shear rates. No significant
      correlation was found between EA at high and low shear rates and fibrinogen
      levels in diabetic subgroups and control subjects. The data suggest that patients
      with type 2 diabetes who had developed clinically evident late complications have
      enhanced EA regardless of the degree of metabolic control. Whether enhanced EA is
      a primary phenomenon contributing to the development of these complications or it
      occurs secondary to their development remains to be clarified.

PMID- 10077354
TI  - Relation between the serum level of C-peptide and risk factors for coronary heart
      disease and diabetic microangiopathy in patients with type-2 diabetes mellitus.
AB  - Syndrome X is used to describe a constellation of factors that lead to coronary
      heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance,
      and an abnormality in lipid metabolism. We investigated the relationship between
      serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in
      256 patients with type-2 diabetes mellitus. The serum level of CPR was measured
      by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according
      to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n
      = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index
      (BMI) and the serum level of triglycerides were significantly higher in the high
      CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence
      of hypertension was significantly higher in the high CPR group than in the other
      2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the
      number of patients receiving insulin therapy was greater in the low CPR group
      than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The
      serum CPR level was significantly lower in patients with than without
      proliferative retinopathy or macroalbuminuria. Our conclusion is that the present
      data suggest that an increased serum level of CPR is associated with obesity,
      elevated serum triglycerides, and hypertension in patients with type-2 diabetes
      mellitus. A low CPR level leading to hyperglycemia is associated with the
      progression of diabetic microangiopathies, such as retinopathy and nephropathy.

PMID- 10077355
TI  - Relation of free and specifically bound leptin to insulin secretion in patients
      with impaired glucose tolerance (IGT).
AB  - Impaired glucose tolerance (IGT) is frequently associated with an increased fat
      mass and an altered fat distribution. The adipocyte derived hormone, leptin has
      been shown to interact with insulin at various levels and may be intimately
      involved in this process. However, only limited data concerning the interaction
      of insulin, glucose tolerance and leptin are available and no data exist on the
      potential influence of bound vs. free circulating leptin. We therefore studied
      free and bound leptin in 136 patients (77 males, 59 females) with IGT, in
      relation to plasma glucose, insulin, proinsulin and C-peptide levels as well as
      serum free and bound leptin concentrations during an oral glucose tolerance test
      (oGTT). The expected positive relation of free serum leptin levels with body mass
      index (BMI) was found. Free leptin concentrations were higher in women than in
      men. Analysis in tertiles revealed a significant relation between free leptin (16
      58, 60-160, and 169-932 pmol/l) and mean fasting insulin levels (65, 93, and 100
      pmol/l). This relationship remained significant in a multiple regression analysis
      with BMI and gender as covariates. Similar independent relationships to leptin
      serum levels were observed for HbA1c and plasma C peptide levels and the
      proinsulin/insulin ratio but not for plasma glucose and proinsulin levels. These
      data suggest a fine tuning of leptin by small changes in circulating insulin
      levels observed in impaired glucose tolerance.

PMID- 10077356
TI  - The inhibition of low density lipoprotein oxidation by 17-alpha estradiol.
AB  - The inhibition of LDL-oxidation by 17-alpha estradiol was assessed in vitro by
      the determination of the duration of the lag-phase in copper ion-induced
      oxidation and compared to that of 17-beta estradiol, estriol, and probucol.
      Addition of 0.2, 0.4, and 1 micromol/l of the test substances prolonged the lag
      phase of LDL-oxidation 1.3-(+/-0.09 SD), 1.7-(+/-0.14 SD), and 2.7-(+/-0.25 SD)
      fold for 17-alpha estradiol; 1.4-(+/-0.14 SD), 1.8-(+/-0.1 SD), and 2.6-(+/-0.16
      SD) fold for 17-beta estradiol; 1.1-(+/-0.07 SD), 1.4-(+/-0.11 SD), and 1.6-(+/
      0.11 SD) fold for estriol as well as 1.4-(+/-0.14 SD), 1.6-(+/-0.1 SD), and 3.0
      (+/-0.21) fold for probucol, thus proving that 17-alpha estradiol is as effective
      as 17-beta estradiol or similar to probucol and more effective than estriol (n =
      6 in all cases). These data demonstrate that 17-alpha estradiol is able to delay
      LDL-oxidation, hence providing a basis for clinical examination of the protective
      effects of 17-alpha estradiol against atherosclerosis in patients where hormonal
      effects of 17-beta estradiol are undesirable.

PMID- 10077357
TI  - Effects of age on GABA turnover rates in specific hypothalamic areas in female
      rats.
AB  - During aging in female rats the estrous cycle ceases and the animals develop
      phases of constant estrous (CE) or constant diestrous (CD) prior to the
      irreversible transition into anestrous. In young rats, gamma-aminobutyric acid
      (GABA) is of pivotal importance for the release of GnRH. In the medial-preoptic
      area (MPO) where the majority of the GnRH perikarya are located in the rat, GABA
      release decreases at the time of the preovulatory LH surge. The suprachiasmatic
      nucleus (SCN) contains numerous GABA neurons. Neurochemical signals from this
      hypothalamic nucleus provide temporal information to GnRH neurons and thereby
      influence the preovulatory LH surge and the length of estrous cycles. To
      investigate aging-related changes of the activity of hypothalamic GABAergic
      neurons, we determined GABA turnover rates in various hypothalamic nuclei of CE
      and CD rats and compared them to those determined in young estrous (E) or
      diestrous rats (D1). In old female rats, GABA activity in the MPO was
      significantly decreased compared to E and D1 rats. A selective increase of GABA
      turnover rates was observed in the SCN of CE animals. No age-related changes were
      observed in the other examined brain areas. These data provide the first evidence
      for alterations in GABAergic activity in specific hypothalamic areas that depend
      on age and reproductive status. These may cause changes in ability to induce
      preovulatory LH surges and to maintain regular estrous cyclicity.

PMID- 10077358
TI  - Pharmacokinetics of new testosterone transdermal therapeutic systems in
      gonadotropin-releasing hormone antagonist-suppressed normal men.
AB  - In a phase I single-center, open, randomized pilot study with a three-way cross
      over design the pharmacokinetics of three testosterone-containing transdermal
      therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS
      HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of
      adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1,
      high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To
      eliminate the influence of endogenous serum testosterone, the endogenous
      testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all
      subjects under GnRH antagonist treatment a marked suppression of LH, FSH,
      testosterone, DHT and estradiol was observed. Physiologic testosterone levels
      were achieved during the 24-hour-application period. Maximal serum levels were
      reached after 4 hours with both TTS systems. Both systems appear suited for
      further testing because both enable a physiological circadian profile to be
      achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect
      of exogenous testosterone in clinical studies, when, due to fluctuations in
      endogenous hormone levels, an estimation of the proportion of exogenous steroid
      is not possible.

PMID- 10077359
TI  - The efficacy of long term thyrostatic treatment in elderly patients with toxic
      nodular goitre compared to radioiodine therapy with different doses.
AB  - The objective of the study was to investigate the efficacy of long term
      thyrostatic versus radioiodine treatment of hyperthyroidism in old age. Our study
      is a retrospective analysis of the therapeutical outcome in 66 patients over 60
      years of age with toxic nodular goitre. The patients were divided in two groups:
      Group A: 28 patients on methimazole treatment: starting dose 5-30, median (M) 10
      mg, maintenance dose 2.5-15 (M = 5) mg, follow up 6 to 240 months (M = 23.5
      months). Group B: 38 patients treated by either 100-300 MBq (N = 14, subgroup B1)
      or 325-1000 MBq (N = 24, subgroup B2) 131I, follow up: 18 to 156 months (M = 48
      months). The efficacy of the different therapeutical approaches were compared by
      calculating the occurrence rate of persisting and relapsing thyroid dysfunctions
      and associated side effects. The 28 patients on methimazole treatment became
      euthyroid after 1-16 (M = 5) months but numerous relapses occurred in the follow
      up: hyperthyroidism, clinical: 5, subclinical 13, (relapse duration: M = 8
      months; associated symptoms: hypertension in 4, cardiac arrhythmia in 3, cerebral
      embolism in 1, angina pectoris in 2, weight loss in 2 cases). Poor patient's
      compliance (9/28) or dose reduction by the physician (5/28) were the main causes
      of the relapses. Transient clinical (3 cases) or subclinical (6 cases)
      hypothyroidism also occurred (duration: 1-3 M = 2 months, no clinical symptoms).
      In 7 out of 14 (50%) patients receiving 100-300 MBq 131I (Group B1)
      hyperthyroidism persisted (versus 4/24 -16.7%- in Group B2 following 325-1000 MBq
      131I; chi2(1) = 4.78 P = 0.028), methimazole treatment had to be continued in
      9/14 patients (64.3%) (versus 5/24 -20.8%)- in Group B2., chi2(1) = 7.18 P =
      0.0074) and in 5/14 (35.7%) the radiotherapy had to be repeated (versus 5/24 
      020.8%- in Group B2, not sign.). Our conclusions are: 1) long term thyrostatic
      treatment is not safe in elderly patients with toxic nodular hyperthyroidism,
      mainly because of poor compliance or dose reduction by the physician; 2)
      radioiodine treatment as the first choice should be recommended for these
      patients and higher doses should be preferred.

PMID- 10077360
TI  - The effect of N-nitro-L-arginine methyl ester on morphine-induced changes in the
      plasma corticosterone and testosterone levels in mice.
AB  - Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester
      (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma corticosterone
      and testosterone levels were studied in male mice. Acute morphine administration
      (15 and 30 mg/kg i.p.) enhanced the corticosterone level after 1 and 2 hr (at a
      dose of 30 mg/kg only). A 4-day treatment with increasing doses of morphine, from
      15 to 50 mg/kg i.p., increased the plasma corticosterone concentration at 2 hr
      after the last injection. Single administration of L-NAME (30 mg/kg i.p.) had no
      effect on the corticosterone level, whereas its repeated injections (30 mg/kg
      i.p., twice a day for four days) elevated the hormone concentration at 2 hr after
      the last dose. Pretreatment of mice with L-NAME enhanced the stimulatory effects
      of both acute and repeated morphine administration on the corticosterone level. D
      NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor,
      had no effect on the morphine-induced changes in the corticosterone level. Acute
      morphine administration had no effect on the plasma testosterone level after 1 or
      2 hr, whereas repeated drug injections decreased the hormone concentration after
      2 hr. Single or repeated L-NAME administration did not influence the testosterone
      level in either control or morphine-treated animals. The above results indicate
      that inhibition of nitric oxide synthase enhances the stimulatory effect of
      morphine on corticosterone secretion, but does not influence the inhibitory
      effect of repeated morphine on the plasma testosterone concentration in mice.

PMID- 10077361
TI  - Effects of the GABA-A receptor agonist and antagonist on the in vitro release of
      hypothalamic catecholamines: apparent parallelism between these effects and the
      LHRH secretion in adult male rats.
AB  - GABA (gamma-aminobutyric acid) has a well-known inhibitory effect on the
      luteinizing hormone-releasing hormone (LHRH) secretion. In order to evaluate the
      contribution of the catecholaminergic neurotransmitters on the inhibitory effect
      produced by GABA on the LHRH release, we measured in adult male rats the in vitro
      hypothalamic output of LHRH, epinephrine (E), norepinephrine (NE) and dopamine
      (DA); after the administration of, either muscimol 1 microM (GABA-A agonist),
      and/or 1 microM bicuculline (GABA-A antagonist). The following results were
      obtained: muscimol inhibited LHRH secretion, and this effect was accompanied by a
      decrease of NE, E and DA output. The opposite effects were observed after the
      addition of bicuculline, i.e, stimulation of LHRH, NE, E and DA release. In
      conclusion, our results show that, in the adult male rats, GABA has an inhibitory
      effect on the in vitro release of LHRH, acting on the GABA-A receptor. This
      effect on LHRH secretion might be exerted directly, or indirectly, by altering
      the release of either NE,E, and/or DA.

PMID- 10077362
TI  - Acute reserpine treatment alters the catecholamine, glucocorticoid and opioid
      response to walking exercise in sheep.
AB  - The aim of the study was to examine the effects of reserpine on the plasma levels
      of adrenaline, noradrenaline, cortisol and alpha-neoendorphin in sheep under
      control conditions and during walking exercise. One hour of walking (5 km/h)
      caused a significant increase in both catecholamines and cortisol between 10 and
      30 min of stress, and transiently decreased the level of alpha-neoendorphin at
      the same time. Reserpine at the dose of 0.3 mg/kg i.v. given before stress
      significantly lowered the basal levels of all tested parameters. A combination of
      the reserpine and walking exercise significantly attenuated the stress-induced
      changes in the plasma level of measured hormones.

PMID- 10077363
TI  - Blunted nocturnal TSH surge does not indicate central hypothyroidism in patients
      after pituitary surgery.
AB  - The thyrotropin-releasing hormone stimulation test (TRH test) is commonly used as
      part of the endocrine evaluation after pituitary surgery. However, some patients
      with a normal thyrotropin (TSH) response to TRH after pituitary surgery develop
      central hypothyroidism during follow-up. On the other hand, hypothyroidism does
      not necessarily ensue in patients with a blunted TSH response. As TSH is secreted
      in a pulsatile fashion with maximum secretion in the early morning, we
      investigated whether measurement of the nocturnal TSH surge is useful for
      predicting development of thyrotropic function after pituitary surgery. Serum TSH
      concentrations were measured at hourly intervals from 16.00 h to 06.00 h in 13
      healthy volunteers and in 10 patients within 2 weeks after pituitary surgery. A
      standard TRH test using i.v. injection of 200 microg synthetic TRH was performed
      the next morning. Three and six months later thyroid function was reassessed in
      all patients by measuring thyroid hormones and TSH. Healthy volunteers showed a
      clear nocturnal TSH surge from a nadir of 0.55 +/- 0.27 microIU/ml at 18.00 h to
      a peak concentration of 1.82 +/- 0.97 microU/ml at 06.00 h (p = 0.0015). DeltaTSH
      during TRH test was 6.31 +/- 2.27 microIU/ml. In contrast, following pituitary
      surgery, patients invariably showed a blunted nocturnal increase in TSH
      concentration, which was 0.27 +/- 0.20 microIU/ml at 18.00 h and 0.33 +/- 0.26
      microIU/ml at 06.00 h (p = 0.044). DeltaTSH during TRH test was 1.99 +/- 2.51
      microIU/ml and was subnormal in 8 out of 10 patients. Levothyroxine
      supplementation was initiated in two of these patients, because free T4 levels
      were also subnormal and clinical hypothyroidism was present. In the remaining
      patients with subnormal TRH response, no case of central hypothyroidism was
      identified at the follow-up visits after 3 and 6 months. We conclude from these
      data that both nocturnal TSH surge and TRH test are subnormal after pituitary
      surgery and do not indicate that central hypothyroidism will develop.

PMID- 10077364
TI  - Acromegaly in a family without a mutation in the menin gene.
AB  - Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly
      have been reported. A third of the cases (30%) is related to multiple endocrine
      neoplasia type 1 (MEN 1). We report two cases of acromegaly in one family with
      pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone
      (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the
      glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years
      later her 24-year-old son also presented with typical signs of acromegaly. A
      pituitary macroadenoma was identified by MRT and he also underwent
      transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or
      other forms of endocrine hyperfunction in the two patients. In an attempt to
      identify the molecular etiology of the tumours DNA was extracted from paraffin
      fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to
      10 of the menin gene were amplified by PCR. Although Gsp mutations have been
      identified in 40% of somatotroph tumors, direct sequencing of the PCR products
      showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were
      found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than
      Gsp or menin gene mutations have to be considered as the molecular etiology of
      acromegaly in this family.

PMID- 10077365
TI  - The place of bronchoscopic photodynamic therapy in advanced unresectable lung
      cancer: experience of 100 cases.
AB  - OBJECTIVES: The objectives of the study were: (1) to evaluate effectiveness of
      photodynamic therapy (PDT) for symptom palliation in patients with inoperable
      lung cancer; (2) to determine survival benefit in a subset of patients. METHODS:
      One hundred patients, 68 male, 32 female, aged 44-81 years (mean 62.5) with
      advanced inoperable bronchogenic cancer and endobronchial luminal obstruction
      were prospectively studied. Eighty-two percent had previous chemo/radiotherapy.
      The pre-treatment protocol consisted of: clinical, radiological and bronchoscopic
      examination, pulmonary function testing, assessment of WHO performance status and
      clinical staging. Treatment protocol was: intravenous injection of 2 mg/kg body
      weight of photofrin/polyhaematoporphyrin and interstitial illumination using 630
      nm laser light 24-72 h later. Follow-up was at 6-8 weeks for 1 year. Then every 3
      6 months if applicable. Repeat PDT as necessary. RESULTS: All patients were stage
      IIIa-IV. The histology of the tumour was: non small cell in 90 and small cell in
      10. There was no treatment related mortality. Mean endoluminal obstruction fell
      from 85.8% to 17.5%, mean forced vital capacity (FVC) and forced expiratory
      volume in 1s (FEVI) improvement was 430 ml and 280 ml, respectively. Ninety
      patients died from 6 weeks to 37 months, mean and median survival: 9 months and 5
      months, respectively. Ten patients are alive from 13 to 72 months, mean 36
      months, median 29 months. Overall 2-year survival was 19%. Multivariant analysis
      indicated that age, sex, histology and stage of disease did not influence
      survival significantly but performance status did. Patients with WHO < 2 had mean
      and median survival of 17.8 and 14 months versus WHO > 2, 6.9 mean and 4 months
      median survival (log-rank P < 0.0001). CONCLUSIONS: (1) PDT is effective in
      palliation of inoperable advanced lung cancer. (2) Subset of patients with a
      better performance status have added survival benefit.

PMID- 10077366
TI  - The threshold for air leak: stapled versus sutured human bronchi, and
      experimental study.
AB  - BACKGROUND: Little is known about the integrity of staple-closure of the bronchus
      and its tolerance to normal mechanical stresses (cough, sneezing, etc.) in the
      immediate early post-operative period. There are few studies which tested the
      mechanical strength of stapled bronchial closure compared with manually closed
      bronchi using the threshold for fluid leak across the bronchial suture line which
      differs from air. MATERIAL AND METHODS: Intact cadaveric tracheobronchial tree (n
      = 40) were selected, age range from 55 to 70, of which 60% were males. They were
      divided into two groups: group A, 20 left bronchi were closed with RLV 30 Ethicon
      4.8 mm bronchial stapler; group B, 20 were closed with 4 0 Prolene simple
      interrupted sutures. All specimens were intubated with endotracheal tube and
      submerged under water before testing the immediate air leak with the standard 40
      mm Hg inflation pressure. Inflation pressure was increased until air leak was
      detected. The stapled closures were resected and subjected to radiological
      examination. RESULTS: No air leak was detected in any bronchus at 40 mmHg
      regardless of the closure technique. The median leakage pressure was
      significantly higher in the hand sutured bronchi compared to the stapled group
      (200 vs. 105 mmHg, respectively) and 50% (n = 10) leaked from multiple sites in
      the stapled group compared with leakage from one site only in group B, this
      difference was statistically significant P < 0.001. The radiological appearance
      of the staples maintained the B configuration, recommended by the manufacturer as
      a sign of sound application. CONCLUSION: Hand sutured bronchi tolerated higher
      inflation pressure compared with the stapled ones before leaking air. Air leak at
      high pressure occurs in the presence of intact staples.

PMID- 10077367
TI  - Clinical spectrum of congenital cystic disease of the lung in children.
AB  - OBJECTIVES: Congenital cystic lesions of the lung are uncommon but share similar
      embryologic and clinical characteristics. The purpose of this study is to review
      our institutional experience of congenital cystic lung disease, emphasizing the
      clinical spectrum of the disease related to age, and present some cases with
      unusual clinical manifestations. PATIENTS: Between 1962 and 1996, 26 patients (9
      females and 17 males) under 15 years old underwent evaluation and surgical
      treatment for congenital cystic lung disease. Seven patients were under 1 year
      old, and 19 were in over 1 year old. There were 13 bronchogenic pulmonary cysts,
      6 pulmonary sequestrations, 4 congenital cystic adenomatoid malformations (CCAM),
      and 3 congenital lobar emphysemas. RESULTS: All patients under 1 year old showed
      respiratory distress with mediastinal shift but no episodes of infection. In
      contrast, 13 of the 19 patients over 1 year old had symptoms of recurrent
      infection without respiratory distress. Five patients over 1 year old were
      entirely asymtomatic from birth. There were significant differences (P < 0.05) in
      the frequencies of respiratory distress and infection between the two groups
      (chi2-test). Lobectomy was performed in 21 patients, excision in 3 patients,
      segmentectomy in one patient, and exploration in one patient. There was no
      incident of postoperative mortality or morbidity except for one patient with CCAM
      complicated by reexpansion lung edema. Twenty-one patients at long-term follow-up
      from 2 to 30 years after surgery are doing well with no subsequent limitation of
      physical activities due to lung resection. CONCLUSIONS: In patients under 1 year
      old, cystic lesions were discovered by respiratory distress; and in patients over
      1 year old signs of infection were the most important clinical features. Early
      recognition of these relatively rare congenital cystic lung lesions would lead to
      the immediate, proper surgical intervention.

PMID- 10077368
TI  - Closure of atrial septal defects via limited right anterolateral thoracotomy as a
      minimal invasive approach in female patients.
AB  - OBJECTIVE: The closure of atrial septal defects via sternotomy is a low-risk and
      high-benefit procedure. Limited right anterolateral thoracotomy is an alternative
      approach with regard to cosmetic aspects. However, it is discussed that a lateral
      approach is not appropriate for more complex lesions and is associated with an
      increased incidence of phrenic nerve damage. METHODS AND RESULTS: The
      perioperative and long-term outcomes (mean follow-up time: 73.2 months) of 87
      female patients, mean age 20.4 years (range: 3-56 years), operated on for all
      types of atrial septal defects via limited right anterolateral thoracotomy
      between 1982 and 1993, were analysed retrospectively. Special features of the
      operation technique were a limited skin incision, protection of mammary gland
      tissue, prevention of phrenic nerve damage, and aortic cannulation in all
      patients. There were no intraoperative complications. Postoperative complications
      occurred in 12/87 patients including one rethoracotomy for postoperative bleeding
      and one late pericardial tamponade due to coumadine overdose. Follow-up was
      assessed by a survey obtained by the patients or their parents, and their family
      doctors in 79 patients (90.8%) Cardiac symptoms, mostly supraventricular
      arrhythmias, were observed in 13.9%. Echocardiography revealed mild tricuspid
      valve regurgitation (one patient) and mild mitral valve incompetence (one patient
      with ostium primum defect); there were no residual shunts. Cosmetic results were
      considered good and excellent in 87.3% and satisfactory in 8.9%. Three patients
      (3.8%) complained of a broad scar. Anaesthetic areas and optional scar pain were
      quite frequent (16.5%), whereas restriction of shoulder movement, breast
      asymmetry and scoliosis were rare. In summary, only one patient, suffering from
      intercostal neuralgia, would prefer sternotomy. CONCLUSION: Limited right
      anterolateral thoracotomy has a high cosmetic acceptance and was proven to be
      safe and effective for closure of any kind of atrial septal defects. Therefore,
      it is recommended as standard approach for atrial septal defects especially in
      female patients. reserved.

PMID- 10077369
TI  - Gender differences in patients with severe aortic stenosis: impact on
      preoperative left ventricular geometry and function, as well as early
      postoperative morbidity and mortality.
AB  - OBJECTIVE: In patients with severe aortic stenosis, we studied the impact of
      gender on preoperative left ventricular geometry and function, as well as on
      early postoperative mortality and morbidity. METHODS: Prospective Doppler
      echocardiographic evaluation was performed in 99 female patients and 96 males.
      RESULTS: The patients had severe aortic stenosis and the mean pressure gradients
      were similar in females and males. Left ventricular diastolic volume adjusted for
      body surface area (BSA) was larger in males, 55+/-17.4 ml/m2 versus 43+/-13.1
      mL/m2 (mean+/-standard deviation; P = 0.0001). The ejection fraction was similar
      in females (55+/-14%) and males (55+/-13%), and patients of both sexes had
      significantly lower stroke volume and cardiac index than healthy controls. The
      relative wall thickness (wall thickness/diastolic diameter ratio) was higher (P =
      0.03) in females (0.47+/-0.10) than in males (0.43+/-0.10) Consequently, the
      diastolic diameter/wall thickness ratio (a substitute for wall tension) was
      higher (P = 0.02) in males (4.2+/-0.99) than in females (3.9+/-0.80). Compared
      with survivors, patients who died within 30 days of the operation (n = 17, 11
      females) had a smaller body surface area (1.70+/-0.19 vs. 1.82+/-0.19 m2, P =
      0.012), smaller left ventricular outflow tract (20.8+/-0.21 vs. 22.0+/-0.22 mm, P
      = 0.023), higher incidence of abnormal intraventricular flow velocity (33 vs. 8%,
      P = 0.018) and increased relative wall thickness (0.52+/-0.17 vs. 0.45+/-0.09 P =
      0.039). Gender was of no independent importance for early mortality when age and
      left ventricular outflow tract diameter were accounted for. CONCLUSIONS: Cardiac
      adaptation to aortic stenosis seems to be influenced by gender, males presenting
      larger left ventricular volumes and higher wall tension. The echocardiographic
      findings of a narrow left ventricular outflow tract, abnormally increased
      intraventricular velocity and increased relative wall thickness identified
      patients with increased risk of early postoperative mortality. However gender had
      no independent impact on early postoperative outcome.

PMID- 10077370
TI  - Stentless or stented aortic valve implants in elderly patients?
AB  - OBJECTIVE: To assess differences in indication and mid-term results between
      stentless and stented procedures in elderly patients, we followed aortic valve
      patients over a period of 5 years. METHODS: In a consecutive series of 154
      elderly aortic patients in regular sinus rhythm from 1992 to 1997, we inserted
      103 stentless (Toronto SPVTM, St Jude Medical Inc., St Paul, Minneapolis, MN) and
      51 stented (Carpentier-Edwards supra annular porcine, Baxter Inc., Irvine, CA)
      bioprostheses in the aortic position. RESULTS: All 154 patients seemed
      preoperatively eligible for a stentless procedure. Mean age was 74.8 years (range
      67-86 years) with a majority of female patients. The surgeon's (in)experience,
      major dilatation or calcifications of the ascending aorta and aberrant coronary
      anatomy were the most common reasons for drawback from the stentless procedure
      (51/154 patients). Aortic clamp time was significantly higher in the stentless
      vs. stented group (70 vs. 57 min, P < 0.0001). The large average 25.3 mm size of
      the stentless prostheses (vs. 23.7 mm stented) stands in full contrast with the
      low mean body surface area of 1.68 m2 (vs. 1.70 m2) of the patients. We
      encountered. respectively. 5 and 2 hospital-deaths (P = n.s.). The follow-up
      period ranged from 6 to 66 months and was 97% complete, yielding, respectively,
      302 and 139 patient-years. Survival (Kaplan-Meier method) was statistically
      higher in favor of the stentless procedures (log rank: P = 0.03). All survivors
      progressed markedly to a mean postoperative NYHA class 1.3 respectively, 1.4 (vs.
      preop. 3.3 and 3.2). Echocardiographic transvalvular gradients compared favorable
      for the stentless group in the small under 25 mm valves (P = 0.02 for 23 mm sized
      valves between groups) with improved left ventricular function and a significant
      decrease of left ventricular end diastolic diameter (LVEDD 48.0 vs. 56.5 mm) at 1
      year follow-up. Cusp calcifications on control echocardiography were detected
      earlier (beyond 3 years) in the stented group, without signs of early significant
      regurgitation or dysfunction in both groups, except for one patient necessitating
      re-operation. CONCLUSION: Although the implantation technique is much more
      demanding for stentless procedures, reflected by a longer aortic clamp-time, and
      remains impossible in some cases, elderly, small sized patients take full benefit
      of their large, non-obstructive prostheses.

PMID- 10077371
TI  - Airway epithelium of transplanted lungs with and without direct bronchial artery
      revascularization.
AB  - OBJECTIVE: Normal systemic blood flow to the airways and lung parenchyma of
      transplanted lungs can only be re-established by direct bronchial artery
      revascularization. The purpose of the present study was to investigate whether
      such direct bronchial artery revascularization would preserve ciliary function,
      previously shown to be reduced in lungs transplanted without revascularization.
      METHODS: Twenty-five single lung transplanted patients were included in this
      study. Complete direct bronchial artery revascularization was achieved in eight
      patients. In 16 patients the procedure had either failed (n = 10) or was not
      attempted (n = 6). In one patient the result of the revascularization was
      unknown. Airway epithelium samples were obtained from the native and the
      transplanted lungs during bronchoscopic examinations. Airway erythema and
      excessive secretion were registered. The epithelium samples underwent
      histological examination and ciliary beat frequency was measured in vitro by
      video recording. Transbronchial biopsies from the transplanted lungs were
      examined for signs of rejection and bronchitis. RESULTS: No differences in
      ciliary beat frequency nor in the distribution of ciliated/de-ciliated columnar
      epithelium cells between native lungs and transplanted lungs with or without
      successful direct bronchial artery revascularization could be demonstrated. In
      38% of the transplanted lungs without successful revascularization metaplastic or
      squamous epithelium was present, while lungs with successful revascularization
      had only normal columnar epithelium. Ongoing rejection or airway erythema did not
      influence ciliary beat frequency. Excessive secretion in the airways was the only
      finding associated with significantly increased ciliary beat frequency.
      CONCLUSIONS: Ciliary beat frequency of epithelium cells of transplanted lungs did
      not differ from that of native lungs and consequently direct bronchial artery
      revascularization did not have any demonstrable important influence. Excessive
      secretion in the airways was associated with increased ciliary beat frequency.
      The histological findings also showed that the abundance of ciliated cells was
      preserved in transplanted bronchi irrespective of bronchial artery
      revascularization. However, epithelium metaplasia was only seen in transplanted
      bronchi without revascularization.

PMID- 10077372
TI  - A prospective study of wound infection in coronary artery surgery.
AB  - OBJECTIVE: The incidence of wound infection in coronary artery surgery is low,
      but there is an appreciable mortality associated with sternal infection. In other
      fields of surgery there is evidence that an all disposable paper gown and drape
      system has protective advantages over a fabric system. Using an established wound
      scoring system (ASEPSIS), we investigated this in a prospective, randomised trial
      of patients undergoing cardiac surgery. METHODS: 505 patients undergoing isolated
      coronary artery surgery in a single hospital over an 18 month period were
      randomised to either a disposable, paper drape system or re-usable fabric drapes.
      Allocation was stratified according to whether or not the patient had had
      previous coronary artery surgery. Patients were followed for 3 months. Total
      infection scores for each wound were calculated from daily scores collected in
      hospital together with the scores at six weeks and three months. RESULTS: The two
      randomised groups were otherwise well matched. Full follow-up information was
      available for 464 (92%) patients. There was no evidence of any difference in
      rates of sternal or leg wound infection between the two groups (P = 0.87 and
      0.62, respectively). Women were more likely to have infected sternal wounds (P =
      0.17) and significantly more likely to have infected leg wounds (P = 0.04).
      Patients with sternal wound infections had a significantly higher body mass index
      (P = 0.001). High Parsonnet scores and increased time on ventilation were
      significantly associated with leg wound but not sternal infections. For both
      wound sites, patients with infections had spent longer in the operating theatre.
      CONCLUSION: In a randomised controlled study of patients undergoing coronary
      artery surgery we found that the use of paper drapes and gowns conferred no
      benefit over a reusable fabric in terms of post-operative wound infection.
      Although females and diabetics are more likely to experience this complication,
      an important additional risk factor is an extended operating time.

PMID- 10077373
TI  - Immediate and long-term results of coronary revascularization in patients
      undergoing chronic hemodialysis.
AB  - OBJECTIVE: To evaluate morbidity and long-term survival in end stage renal
      disease (ESRD) patients, undergoing coronary artery bypass graft surgery.
      METHODS: We identified 22 such patients who underwent bypass grafting between
      1987 and 1997. Symptomatic status of angina was rated using the classification of
      the Canadian Cardiovascular Society (CCS) and the functional status, was assessed
      using the Karnofsky scoring system. The patients were hemodialyzed the day before
      surgery and 24-48 h after surgery. RESULTS: Two patients operated on for acute
      myocardial infarction died after 4 days. Follow-up was completed in the remaining
      20 patients (the mean follow-up time was 25+/-15 months). The survival rates at
      1, 2 and 3 years was 84.5%, 74% and 59%, respectively. The symptoms diminished
      and the functional status was significantly improved. CONCLUSION: We conclude
      that elective coronary artery bypass in dialysis patients can be performed with
      acceptable morbidity and mortality. We advocate early surgical treatment.
      However, long-term survival is limited and this requires further investigation.

PMID- 10077374
TI  - Tolerance to ACE inhibitors after cardiac surgery.
AB  - OBJECTIVES: Several studies have shown angiotensin-converting enzyme (ACE)
      inhibitors to confer significant mortality and morbidity benefits in heart
      failure. First-dose hypotension may necessitate interruption of such therapy.
      This is more likely to occur if the ACE inhibitor is administered early after
      coronary artery bypass grafting (CABG). The purpose of this study was to analyse
      the haemodynamic tolerance to early post-operative treatment with perindopril and
      enalapril in patients with impaired renal and ventricular function. METHODS:
      Eighty one consecutive CABG patients with a previous myocardial infarction,
      impaired pre-operative left ventricular ejection fraction (LVEF) on
      ventriculography and moderately impaired renal function (serum creatinine of 115
      150 micromol/l) were randomised into three groups to receive oral placebo,
      perindopril (4 mg) or enalapril (5 mg) once daily. Groups were subdivided into
      those with mild ventricular dysfunction (LVEF = 35-65%, n = 20) and significant
      ventricular dysfunction (LVEF < 35%, n = 7). Exclusion criteria included oliguria
      (<0.5 ml/kg per h) or inotrope dependance at the point of entry on the first post
      operative day. Intolerance to ACE inhibitor was defined as hypotension (<95 mmHg
      systolic blood pressure or a decrease exceeding 25 mmHg in systolic blood
      pressure) leading to oliguria (<0.5 ml/kg per h) which was unresponsive to
      intravenous furosemide (20 mg). In such cases ACE inhibitor treatment was
      discontinued and patients commenced on dopamine. RESULTS: In the groups with mild
      ventricular dysfunction (LVEF = 35-65%) perindopril was discontinued in 1/20 and
      enalapril in 4/20 patients (P = n.s). However, in the groups with significant
      ventricular dysfunction (LVEF < 35%) perindopril was discontinued in 2/7 and
      enalapril in 7/7 patients (P = 0.02). CONCLUSION: Our results suggest that after
      CABG, patients with moderately impaired renal function and significant
      ventricular dysfunction do not tolerate ACE inhibitors well when these were
      commenced on the first post-operative day. However, perindopril was associated
      with less haemodynamic deterioration than enalapril and consequently may be
      advantageous in this setting. rights reserved.

PMID- 10077375
TI  - Cardiac surgery in the elderly.
AB  - OBJECTIVE: There has been a gradual increase in the number of elderly patients
      referred for cardiac surgery. These patients present a difficult challenge, they
      are usually symptomatic yet at high risk for intervention. The aim of this study
      is to review our experience with cardiac surgery in patients aged 80 years or
      older. PATIENTS AND METHODS: Between January 1981 and October 1997, 242 patients;
      135 female, 107 male, mean age 82.8 years (range 80-95) underwent surgery on
      cardiopulmonary bypass in our unit. Surgery was performed on 14 as an emergency
      and 136 on an urgent (patient restricted to a hospital bed due to symptoms)
      basis. Pre-operatively 182 (75.2%) were in NYHA functional class 3 or 4. RESULTS:
      Early mortality was 14 (5.7%). A mitral valve procedure and emergency surgery
      were significantly associated (P < 0.05) with an increased risk of operative
      mortality. Median ITU and in-hospital stay was 1 day (range 0-33) and 10 (range 6
      49) days, respectively. Ninety-three percent of patients were living
      independently at home 2 months post-operatively. Survival (+/-SEM) is 98%
      complete (totals 557 patient years) and including early mortality at 1 and 5
      years was 85.5+/-2.4% (n = 154), and 67.7+/-4.3% (n = 33). Survival for patients
      undergoing isolated aortic valve replacement (AVR) and coronary artery bypass
      grafting (CABG) at 5 years was 64.8+/-7.8% and 79.7+/-7.4%, respectively.
      Survival was significantly worse in patients undergoing a mitral procedure. Using
      Cox's proportional hazards model only type of operation (mitral surgery) was
      significantly associated with worse survival. CONCLUSION: Cardiac surgery can be
      performed in a selected elderly population with a low operative mortality. Post
      operatively elderly patients attain an excellent quality of life and survival.
      Emergency and mitral surgery in this group of patients is less rewarding.

PMID- 10077376
TI  - Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.
AB  - OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker
      (esmolol)-enriched normothermic blood during cardiac surgery has been suggested
      as an alternative technique for myocardial protection. The aim of the present
      study was to compare the beta-blocker technique to Buckberg's blood cardioplegia
      during coronary artery bypass grafting (CABG). METHODS: Sixty patients with
      coronary artery disease were randomly assigned to either the esmolol group (ES, n
      = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES
      patients received continuous normothermic coronary perfusion with esmolol
      enriched blood. Hearts of the BC group were protected by antegrade cold blood
      cardioplegia according to Buckberg. We measured left ventricular (LV)
      contractility using TEE (fractional area of contraction, FAC) and hemodynamic
      parameters prior to cannulation for cardiopulmonary bypass (CPB), after
      decannulation, and 4 h postoperatively. Myocardial lactate release was measured
      prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV
      biopsies for determination of heat-shock protein (HSP-70), actin pattern and
      intercellular adhesion-molecule (ICAM-I) as indicators for structural changes
      were collected prior CPB, at the end of the aortic cross-clamp period, and prior
      to weaning off CPB. RESULTS: There was no significant difference between both
      groups with respect to grafts and cross-clamp time. ES hearts did not release
      lactate during cross-clamp. In contrast, BC hearts released significant amounts
      of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation
      showed no difference between groups, whereas at 4 h post CPB measurements showed
      slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus
      BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P <
      0.05). HSP-70 and actin pattern showed no difference between groups; however,
      ICAM-I showed a significantly higher degree of structural changes in BC hearts:
      18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that
      application of the beta-blocker technique during routine CABG was associated with
      slightly better functional recovery and less structural myocardial alteration as
      compared with intermittent cold blood cardioplegia, however, both techniques
      provided equivalent myocardial protection in terms of patient outcome. Future
      studies are required to investigate if myocardial ischemia minimization by use of
      the beta-blocker technique may be beneficial in compromized hearts.

PMID- 10077377
TI  - A clinical comparative study between crystalloid and blood-based St Thomas'
      hospital cardioplegic solution.
AB  - OBJECTIVE: Myocardial protection with blood cardioplegia during cardiac surgery
      is increasingly preferred, but few studies have compared the protective effects
      of crystalloid cardioplegia to the same solution with blood as the only variable.
      This clinical study compared the protective effects of crystalloid or blood-based
      St. Thomas' Hospital cardioplegic solution No. 1. METHODS: Fifty higher risk
      patients undergoing elective coronary artery bypass surgery, with an ejection
      fraction less than 40%, were randomly allocated to receive cold (4 degrees C)
      intermittent crystalloid St. Thomas' No. 1 cardioplegia (n = 25), or a similar
      blood-based solution (n = 25) with a haematocrit of 10-12%. We determined (1)
      peri-operative and post-operative arrhythmias, (2) left and right ventricular
      function (24 h) using the thermodilution technique, (3) left ventricular high
      energy phosphate content sampled before ischaemia, the end of ischaemia and the
      end of bypass. RESULTS: Pre-operative haemodynamic data, aortic cross-clamp and
      bypass times were similar in both groups of patients; there was no mortality. At
      the end of ischaemia there were no differences in ATP content between groups but
      creatine phosphate was maintained at a significantly (P < 0.007) higher level in
      the blood-based St. Thomas' cardioplegia group than the crystalloid St. Thomas'
      cardioplegia group (20+/-2 (SE) vs. 13+/-1 micromol/g dry wt, respectively).
      Return to spontaneous sinus rhythm was significantly (P = 0.002) increased in the
      blood-based St. Thomas' cardioplegia group (96%) compared to the crystalloid St.
      Thomas' cardioplegia group (60%). Early post-operative ventricular dysfunction
      occurred in both groups, but normal LV function (stroke work index) recovered
      significantly (P = 0.043) more rapidly (by 2 h) in the blood-based St. Thomas'
      cardioplegia group of patients. CONCLUSIONS: In a higher risk (EF < 40%) group of
      patients undergoing elective cardiac surgery, addition of blood to an established
      crystalloid cardioplegic solution significantly enhanced myocardial protection by
      reducing arrhythmias, improving rate of recovery of function and maintaining
      myocardial high-energy phosphate content during ischaemia.

PMID- 10077378
TI  - Hypoglycaemia associated with a solitary fibrous tumour of the pleura.
AB  - We report the interesting case of an elderly woman who presented with
      hypoglycaemic episodes and weight loss. She was found to have a solitary fibrous
      tumour weighing more than 1.7 kg arising from the diaphragmatic pleura, which had
      been producing insulin-like growth factor II. After surgical removal of this well
      encapsulated, pedunculated tumour her hypoglycaemia resolved and she returned to
      normal both clinically and biochemically.

PMID- 10077379
TI  - Pulmonary artery bullet injury following thoracic gunshot wound.
AB  - Thoracic trauma occurs frequently but seldom requires surgery (10-20%, [1]). The
      mortality rate for gunshot wound of the chest varies from 14.3 to 36.8% [2]. We
      report, herein an example of bullet injury to the pulmonary artery (PA) following
      a thoracic gunshot wound. This patient had previous history of coronary surgery.
      Absolute and relative indications for exploratory thoracotomy in emergency will
      be reviewed.

PMID- 10077380
TI  - Percutaneous fenestration of the aortic dissection membrane in malperfusion
      syndrome.
AB  - We present two cases of malperfusion syndrome due to aortic dissection type-B. A
      supra-renal blind sac phenomenon resulted in renal failure and absent femoral
      pulses in both patients. Additionally, one patient suffered from spinal cord
      ischemia, the other from severe abdominal pain. By interventional techniques,
      catheter perforation of the blind sac was achieved. The resulting re-entries were
      enlarged with a balloon catheter. Distal perfusion without pressure gradients was
      restored by this technique in both patients and resulted in complete relief of
      symptoms. Percutaneous fenestration of the aortic dissection membrane may be an
      alternative to operative treatment in malperfusion syndrome.

PMID- 10077381
TI  - Successful total correction of complete atrioventricular canal, total anomalous
      pulmonary venous drainage and unroofed coronary sinus in an infant.
AB  - An infant with complete atrioventricular canal, total anomalous pulmonary venous
      drainage into the left superior vena cava and an unroofed coronary sinus
      successfully underwent total correction. A homograft vein was used to connect the
      proximal left superior vena cava to the right atrium and can be recommended when
      other methods of correction of unroofed coronary sinus cannot be used.

PMID- 10077382
TI  - Pseudoaneurysm of the left ventricle after isolated pericarditis and
      Staphylococcus aureus septicemia.
AB  - Left ventricular pseudoaneurysm after isolated pericarditis as a result of
      Staphylococcal septicemia is very rare. A case of a very young patient is
      described. Diagnosis is made by echocardiography. Immediate surgical resection of
      the pseudoaneurysm is the therapy of choice.

PMID- 10077383
TI  - Cardiac tamponade and death from intrapericardial rupture [corrected] of sinus of
      Valsalva aneurysm.
AB  - A 35-year-old woman presented with dyspnea and chest pain. She had a large
      aneurysm of the non-coronary sinus of Valsalva. Before her scheduled urgent
      surgery, the patient collapsed and died of cardiac tamponade secondary to
      intrapericardial rupture of the aneurysm. We would advocate urgent repair of this
      type of lesion to prevent such an outcome. We are aware of no other specific
      reports addressing extracardiac rupture of non-coronary cusp aneurysms
      [corrected].

PMID- 10077384
TI  - Mitral valve repair for anterior leaflet papillary fibroelastoma: two case
      descriptions and a literature review.
AB  - Cardiac papillary fibroelastomas are rare cardiac tumors and have been considered
      a 'benign' incidental finding that may have significant clinical manifestations.
      In this paper we report two cases of mitral valve fibroelastoma: one was
      discovered by chance with transthoracic echocardiography in a young healthy man,
      the other was an intraoperative incidental finding in a middle aged man with a
      recent history of acute myocardial infarction. The mitral valve was repaired in
      both cases after excising the tumor. The patients did well and remain
      asymptomatic. A literature review was compiled which comprises previous case
      reports of 34 patients with mitral valve papillary fibroelastomas. Most were
      asymptomatic, but when symptoms occurred, they could be disabling, such as
      stroke, cardiac heart failure, myocardial infarction, and sudden death. Papillary
      fibroelastoma is amenable to simple surgical excision or in addition to mitral
      valve repair or replacement. Recurrence has not been reported.

PMID- 10077385
TI  - Aortic dissection limited to the ascending aorta mimicking intramural hematoma.

PMID- 10077386
TI  - Is hypothermia necessary in pediatric cardiac surgery?

PMID- 10077387
TI  - A knot in the heart-surgical removal of a pulmonary artery catheter entangled in
      the tricuspid valve chordae.

PMID- 10077388
TI  - Advaseal for acute aortic dissection: experimental study.

PMID- 10077389
TI  - CarboMedics Prosthetic Heart Valve.
AB  - INTRODUCTION: The CarboMedics Prosthetic Heart Valve has been in use since 1986,
      with more than 220,000 valves implanted through August of 1997 in more than 1550
      centers in more than 100 countries. This paper presents the results of a
      multicenter, international clinical trial that has spanned 10 years. METHODS:
      There were 1128 valves implanted in patients at 10 sites. The mean follow-up for
      patients was 4.5 years, with a total of 5110.1 patient-years. Approximately one
      third of the patients came from the United States, one-third from Canada, and one
      third from Scandinavia. The mean age was 57.2 years; 54.8% were men and 45.2%
      were women. The primary disease was calcification/atherosclerosis in 37% of the
      patients and rheumatic disease in 32.7%, and reoperation accounted for 17.5%.
      There were 556 aortic valve replacements, 428 mitral valve replacements, 139
      double valve replacements, and five tricuspid replacements. RESULTS: The survival
      rate of all implanted patients was 79% at 5 years postoperatively. The survival
      rate in redo valve patients was as good as the primary survival rate; the
      survival rate in double valve patients was not as good as the survival rate in
      single valve patients. There was no structural failure of the valve. Patient
      outcome as described by New York Heart Association class was significantly
      improved throughout the postoperative period. Rates of freedom from thrombosis,
      thromboembolism, and hemorrhage at 5 years were 98.9%, 90%, and 91%,
      respectively. SUMMARY: Clinical results of the CarboMedics Prosthetic Heart Valve
      in a midterm, multicenter study were excellent, with low rates of morbidity and
      mortality and no structural failure.

PMID- 10077390
TI  - Partial left ventriculectomy--the Batista procedure.

PMID- 10077391
TI  - Left ventricular assist device as a bridge to partial left ventriculectomy.
AB  - In 1963, Dr Michael DeBakey successfully implanted the first left ventricular
      assist device. Throughout the 1970s, cardiovascular research aimed to achieve
      long-term circulatory support with such devices; later, as improved medical
      therapy decreased patients' chances of organ rejection or infection,
      transplantation became a viable alternative for the treatment of heart failure.
      At that point, left ventricular assist devices began to be used as bridges to
      transplantation. As left ventricular assist devices were used for longer periods
      of time, we realized that the ventricular function and overall health of the
      patients awaiting transplant improved. Used as a bridge to transplantation, left
      ventricular assist devices often increased a patient's chances of survival and
      recovery. Recently left ventricular assist devices have been used as bridges to
      partial left ventriculectomy (the Batista procedure). Our early experiences with
      this procedure in selected patients have been promising. Many patients recover to
      NYHA functional class I after prolonged left ventricular unloading, surgery, or
      both. In addition, the native heart may be saved, especially in younger patients,
      eliminating the need for transplantations and decreasing the strain on the
      limited organ donor pool.

PMID- 10077392
TI  - Early and intermediate results of left ventricular reduction surgery.
AB  - OBJECTIVE: Left ventricular reduction surgery is a new surgical option for
      treatment of end-stage cardiac dysfunction, and little is known about
      hemodynamics and outcome in the European heart failure population. We present our
      early results with this operation. METHODS: From January 1995 to September 1997,
      30 patients (25 men, 5 women; mean age 61.2 years) underwent partial left
      ventriculectomy. The underlying disease was ischemic in 18 patients and
      idiopathic dilated cardiomyopathy in 12 patients. Preoperatively 23 patients were
      in New York Heart Association functional class IV and 7 were in class III. Mean
      cardiac index, stroke index and ejection fraction were 1.8 +/- 0.3 l/m2 per min,
      23.5 +/- 5.1 ml/m2 and 19.3% +/- 6.8%, respectively. Associated procedures were
      coronary bypass in 18 patients, mitral valvuloplasty in one, aortic or mitral
      valve replacement in three, dynamic cardiomyoplasty in two, and left ventricular
      assist device implantation in 1. RESULTS: There were two early deaths: one from
      bleeding and one from anticoagulant-related cerebral hemorrhage. Regarding late
      deaths, one patient died from pneumonia 3 months after the operation and two died
      from dysrhythmia 4 and 17 months postoperatively. The estimated 1-year survival
      rate calculated by the Kaplan-Meier log-rank method was 85%. Mean cardiac index,
      stroke index, and ejection fraction rose significantly (P = 0.0001) to 2.9 +/-
      0.51/m2 per min, 36.9 +/- 6.2 ml/m2 and 37.8% +/- 9.2%, respectively. Currently
      26 patients are in New York Heart Association functional class I or II.
      CONCLUSIONS: Left ventricular reduction surgery improves objective and subjective
      parameters of cardiac performance significantly in early and intermediate follow
      up. Randomized studies and carefully documented long-term results seem to be
      necessary to define the role of left ventricular reduction surgery.

PMID- 10077393
TI  - Minimal access aortic valve surgery.
AB  - OBJECTIVE: We report our experience with minimal access aortic valve surgery and
      discuss the three approaches used. METHODS: From June 1996 to October 1997, 18
      patients underwent minimally invasive aortic valve surgery through three
      different incisions: right parasternal minithoracotomy (three cases), upper
      ministernotomy (11 cases), and transverse sternotomy (four cases). No special
      surgical instrumentation was used. Aortic valve replacement was carried out in 17
      patients and aortic valve repair in one patient. The patients ranged in age from
      42 to 86 years (mean 64 years). Concomitant procedures involving the aortic root
      and the ascending aorta were performed in five patients. RESULTS: There was no
      mortality and no complications related to the procedure or the access. There was
      no instability or paradoxical movement of the chest wall. One patient was
      reoperated for postoperative bleeding. All patients were discharged from hospital
      within the usual time. No attempts were made to discharge them earlier, even if
      they recovered quickly. CONCLUSIONS: Of the three incisions used, the upper
      ministernotomy seemed to be the safest and easiest to perform. Through this
      incision, both the aorta and the right atrium could be cannulated, the right
      ventricle was accessible, and concomitant procedures on the ascending aorta could
      be carried out. The drawback of minimal access aortic valve surgery in general is
      that it is difficult to de-air the heart and more difficult to master intra- and
      postoperative complications should they occur.

PMID- 10077394
TI  - N-terminal proatrial natriuretic peptide in angina pectoris: impact of
      revascularization by angioplasty.
AB  - AIMS: We investigated whether levels of N-terminal proatrial natriuretic peptide
      (N-terminal proANP) reflect the severity of coronary artery disease in chronic,
      stable angina pectoris. Furthermore, we investigated if revascularization by
      percutaneous transluminal coronary angioplasty (PTCA) affected the N-terminal
      proANP level and, finally, whether restenosis could be predicted by changes in N
      terminal proANP after PTCA. METHODS AND RESULTS: N-terminal proANP was measured
      in 286 patients before and after PTCA. The patients' baseline level of N-terminal
      proANP (787+/-403 pmol/l) correlated significantly with left ventricular end
      diastolic pressure, age and serum creatinine, but not with the number of stenotic
      vessels. Twenty-four hours post-PTCA N-terminal proANP decreased significantly,
      and completely revascularized patients demonstrated a decline two-fold larger
      than those incompletely revascularized (deltaN-terminal proANP -114+/-178 vs. 
      53+/-231 pmol/l, P<0.05). After 14 days N-terminal proANP had returned to
      baseline in both groups. Changes in N-terminal proANP from post-PTCA to the final
      follow-up was not predictive of angiographic restenosis. INTERPRETATION: The
      significant decrease in N-terminal proANP observed after angioplasty, most
      pronounced in patients completely revascularized, is thought to reflect a
      transient improvement in resting left ventricular function.

PMID- 10077395
TI  - Competitive pulmonary flow in infancy: the effect of respiration.
AB  - Superior caval flow during positive pressure mechanical ventilation and
      spontaneous breathing was investigated by Doppler echocardiography in a neonate
      with a coexisting superior cavopulmonary shunt and an aortopulmonary shunt.
      During positive pressure ventilation, retrograde systolic flow in the superior
      vena cava was recorded, with low velocity anterograde flow. This pattern was
      reversed during spontaneous respiration. Low intrathoracic pressure plays an
      important role in maintaining anterograde pulmonary blood flow in patients with
      this physiology.

PMID- 10077396
TI  - Increased severity of viral myocarditis in mice lacking lymphocyte maturation.
AB  - The role of lymphocytes in the pathogenesis of viral myocarditis is
      controversial. To better understand how lymphocyte maturation controls a virus
      induced myocarditic process, a murine model of viral myocarditis was utilized.
      Encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three
      kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and
      recombination activity gene (RAG)-2 knockout 129/SV mice. The RAG2 participate in
      the maturity of T and B lymphocytes. Survival rate, heart weight (HW), HW to body
      weight (BW) ratio, viral genome, cardiac inflammation and myocardial necrosis
      were evaluated after EMCV (500 plaque forming unit/mouse) inoculation. On post
      inoculation day 10, the survival rate of C57BL/6, 129/SV and RAG2 knockout mice
      were 42, 90 and 0%, respectively. Myocardial viral titer was significantly
      (P<0.05) higher in C57BL/6 and RAG2 knockout mice than in 129/SV mice. In situ
      hybridization demonstrated the EMCV genome in the myocardium of RAG2 knockout and
      C57BL/6 mice, but not in 129/SV mice. At day 8, HW and HW/BW ratios were elevated
      (P<0.05) in RAG2 knockout mice as well as C57BL/6 mice compared with 129/SV mice.
      Myocardial necroses were more severe in RAG2 knockout mice than in wild-type
      129/SV mice. In conclusion, matured lymphocytes protect the development of viral
      myocarditis which includes viral replication and myocardial apoptosis.

PMID- 10077397
TI  - Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble
      coenzyme Q10 in patients with coronary artery disease: discovery of a new role.
AB  - OBJECTIVE: To examine the effect of coenzyme Q10 supplementation on serum
      lipoprotein(a) in patients with acute coronary disease. STUDY DESIGN: Randomized
      double blind placebo controlled trial. SUBJECTS AND METHODS: Subjects with
      clinical diagnosis of acute myocardial infarction, unstable angina, angina
      pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were
      randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10
      group, n=25) or placebo (placebo group, n=22) for a period of 28 days. RESULTS:
      Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group
      compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of
      22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase
      in the intervention group without affecting total cholesterol, LDL cholesterol,
      and blood glucose showed a significant reduction in the coenzyme Q10 group.
      Coenzyme Q10 supplementation was also associated with significant reductions in
      thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates,
      indicating an overall decrease in oxidative stress. CONCLUSION: Supplementation
      with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in
      patients with acute coronary disease.

PMID- 10077398
TI  - HLA antigen frequencies in end-stage idiopathic and ischaemic cardiomyopathy.
AB  - We investigated the distribution of HLA antigens among 413 patients with
      ischaemic heart disease or dilated cardiomyopathy referred for cardiac
      transplantation to determine if possession of certain HLA antigens predisposed to
      end-stage heart failure. Of the patients studied, 234 had ischaemic heart disease
      (218 males), mean age 49 years (SD 7.1) and 179 patients had dilated
      cardiomyopathy (150 males), mean age 39 years (12.8). The control group comprised
      2041 kidney donors reported to the United Kingdom Transplant Service between July
      and August 1985. We found a significant excess of HLA DR1 (odds ratio 1.64, 95%
      CI 1.16-2.33, attributable risk 5.0%) and DR5 antigens (odds ratio 1.47, 95% CI
      0.99-2.18, attributable risk) among patients with dilated cardiomyopathy but not
      of HLA DR4 as previously reported. We found a lower frequency than expected of
      HLA B21 (10.44 expected, none observed) among patients with ischaemic heart
      disease but no other significant differences. This study provides some support
      for the concept of the risk of developing end-stage heart failure due to dilated
      cardiomyopathy being associated with possession of HLA DR1 and DR5, but no such
      evidence in ischaemic heart disease. Larger multi-centre studies are required to
      confirm the validity of these findings.

PMID- 10077399
TI  - Decreased left atrial appendage function is an important predictor of elevated
      left ventricular filling pressure in patients with congestive heart failure.
AB  - OBJECTIVE: The aim of this study was to investigate whether left atrial (LA)
      appendage function, as indicated by LA appendage blood flow velocities and its
      ejection fraction, could identify elevated left ventricular filling pressure in
      patients with chronic congestive heart failure. METHODS: Using transesophageal
      echocardiography, adequate pulsed Doppler LA appendage active emptying and
      filling velocities could be recorded in 25 consecutive patients (16 men and 9
      women, aged 57+/-10 years) with chronic congestive heart failure (symptom
      duration > or =1 year). LA appendage ejection fraction calculated as (LA
      appendage maximal area)-(LA appendage minimal area)/(LA appendage maximal area) x
      100 was also determined in these patients. Left ventricular end-diastolic
      pressure was recorded during cardiac catheterization performed within 24 h of
      echocardiographic study. RESULTS: Left ventricular end-diastolic pressure was 2
      to 47 mm Hg. There were close negative correlations of LA appendage emptying
      velocity (r=-0.508; P<0.01), filling velocity (r=-0.429; P<0.05) and LA appendage
      ejection fraction (r=-0.523; P<0.005) with left ventricular end-diastolic
      pressure. LA appendage active emptying velocity <30 cm/s predicted left
      ventricular end-diastolic pressure >25 mm Hg with a sensitivity of 72.7%, a
      specificity of 92.9% and a positive and negative predictive value of 88.9 and
      81.3%. CONCLUSIONS: The findings suggest that measurement of LA appendage blood
      flow velocities and contractile function by transesophageal echocardiography can
      be used to predict elevated left ventricular filling pressure in patients with
      congestive heart failure.

PMID- 10077400
TI  - Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart
      failure and control.
AB  - We studied the effect of intravenous pirenzepine (3 mg) in normal subjects (n=15,
      43+/-16 years old) and in patients with chronic heart failure (n=15, 61+/-12
      years old) to assess the effect of low-dose pirenzepine on vagal activity. R-R
      intervals and the standard deviations, low-frequency power (LF: ln ms2, 0.04-0.15
      Hz), high-frequency power (HF: ln ms2, 0.15-0.40 Hz) and the ratio of low- to
      high-frequency power (LF/HF ratio) were measured 10 min before and after
      pirenzepine using a Holter analysis system. Pirenzepine was found to cause a
      significant increase in the R-R interval from 903+/-112 to 956+/-129 ms in the
      control group (P<0.0001) and from 927+/-141 to 958+/-168 ms in patients with
      chronic heart failure (P<0.01). Pirenzepine also increased HF significantly from
      4.29+/-0.32 to 5.16+/-0.38 ln ms2 in the control group (P<0.0001) and from 4.04+/
      0.16 to 4.48+/-0.24 ln ms2 in the chronic heart failure group (P<0.05).
      Pirenzepine did not significantly alter the LF/HF ratio in either group. We
      emphasize that pirenzepine appears to have a vagoinimetic effect in patients with
      chronic heart failure and that it may be useful for augmenting vagal control of
      the heart in some patients with chronic heart failure.

PMID- 10077401
TI  - Effects of oral repetitive loading of disopyramide on acute-onset atrial
      fibrillation with concurrent monitoring of serum drug concentration.
AB  - We investigated the efficacy and safety of oral repetitive loading of
      disopyramide, for the termination of acute-onset (i.e., therapy started within 2
      days after the onset of palpitations) atrial fibrillation (AF) in 96 consecutive
      patients, with concurrent monitoring of the serum concentration of this agent in
      fifteen of the patients. Outpatients with AF verified by standard
      electrocardiogram (ECG) were hospitalized and received disopyramide (200 mg)
      every 4-6 h, with a maximal dose of 800 mg daily, until the termination of AF
      under ECG monitoring was obtained. Conversion to sinus rhythm occurred within the
      first day of treatment in 88 patients (92%), on the second day of treatment in
      six patients (6%), and on the third and fifth days of treatment in the remaining
      two patients. No major adverse effects, such as hypotension, congestive heart
      failure, proarrythmic events or systemic embolism were noted. The serum levels of
      disopyramide evaluated in fifteen of the enrolled patients were found to be
      maintained within the therapeutic range throughout the treatment period. In spite
      of the absence of any placebo-controlled group in this study, these findings
      suggest that repetitive oral loading of disopyramide (200 mg) with an interval of
      4-6 h is effective and safe for the termination of acute-onset AF under a stable
      therapeutic serum drug concentration, hence offering the possibility of self
      medication for patients with episodic AF.

PMID- 10077402
TI  - Variation in stated management of acute myocardial infarction in five countries.
AB  - We examined the variation in stated practice in the management of acute
      myocardial infarction (AMI) among doctors in Australia, Brazil, Chile, India and
      Thailand. Hospitals were identified as primary, secondary or tertiary by
      investigators from around their own region. All doctors within each hospital who
      would be expected to treat patients with AMI were asked to indicate which
      investigations and treatments they would offer to a patient with an AMI who
      develops angina on Day 3 after admission. The numbers of hospitals ranged from 5
      to 26 per country, and doctor response rates varied from 70 to 100%. Within
      country variation was large, and statistically significant variations were seen
      between countries in the use of most interventions. The large variation both
      between and within a range of countries across the economic spectrum suggests a
      widespread need for agreement about what constitutes appropriate management after
      AMI.

PMID- 10077403
TI  - Intense acute phase response in ischemic patients.
AB  - The aim of this study was to estimate the qualitative and quantitative changes of
      acute phase proteins in patients suffering from coronary heart disease. The study
      was carried out on 74 patients and 12 healthy volunteers. The patients were
      divided into three groups as follows: patients with myocardial infarction (n=37),
      Group I--without heart failure, Group II--with heart failure (II-III NYHA), Group
      III--patients with unstable angina pectoris (n=35); controls-healthy volunteers
      (n=12). The immunological measurements were performed at the beginning of
      hospitalisation (point 0), after 4, 8, 12 and 72 h, and after 6, 9 and 12 days of
      hospitalisation. The concentrations of C-reactive protein (CRP), alpha1-acid
      glycoprotein (AGP) and alpha1-antichymotrypsin (ACT) were measured using rocket
      immunoelectrophoresis according to Laurell. Glycosylation profiles of AGP and ACT
      were determined using crossed affinity immunoelectrophoresis with Con A as ligand
      according to Bog-Hansen. Between Groups I and II statistically significant
      differences were observed for all investigated parameters. Highest concentration
      values were observed for Groups II and III; for Group II they appeared earlier
      than for Group III. The maximal values for reactivity coefficients (AGP-RC and
      ACT-RC) were observed earlier than the respective maximal values of
      concentrations. Continuous activation occurring in unstable angina leads to a
      more rapid increase in the concentrations of acute phase proteins and more marked
      alterations in their glycosylation profiles. In a way these patients seem to be
      'primed' with constant stimulation, so that they respond dramatically to the
      stimulus of ischemia.

PMID- 10077404
TI  - Sinus bradycardia as a predictor of right coronary artery occlusion in patients
      with inferior myocardial infarction.
AB  - Differentiation of right coronary artery (RCA) from left circumflex artery (LCxA)
      occlusion may be difficult since both can present an electrocardiographic pattern
      of inferior myocardial infarction (IMI). We studied 133 patients with IMI, 92
      patients with RCA occlusion and 41 patients with LCxA occlusion. Risk factors
      such as previous MI, arterial hypertension, diabetes, smoking, and dislipemia,
      were similar for RCA and LCxA occlusions. Patients with RCA occlusion had a
      higher incidence of isolated IMI than patients with LCxA occlusion, 50% vs. 17%,
      respectively (P<0.001). Arterial hypotension was more prevalent (P<0.05) among
      patients with RCA (18%) rather than those with LCxA occlusion (2%). RCA occlusion
      presented an association with sinus bradycardia, an association not observed with
      LCxA occlusion (15% vs. 0%, respectively; P<0.01). Total atrioventricular block
      was only present among patients with RCA (18%). Proximal occlusions of the RCA
      presented lower heart rates (sinus bradycardia) than medial and distal occlusions
      (13% vs. 1% and 1%, respectively; P<0.0001 and P<0.001). Therefore, regarding
      patients with IMI: (1) sinus bradycardia is more frequent when the infarct
      related artery is the RCA; (2) proximal occlusions of the right coronary
      predispose low heart rates; and (3) occlusion of the LCxA rarely induces sinus
      bradycardia.

PMID- 10077405
TI  - Prognosis in myocardial infarction survivors with left ventricular dysfunction is
      predicted by electrocardiographic RR interval but not QT dispersion.
AB  - OBJECTIVES: The aim of the study was to assess if QT dispersion and RR interval
      on the standard 12-lead electrocardiogram (ECG) predict cardiac death and late
      arrhythmic events in postinfarction patients with low left ventricular ejection
      fraction (LVEF). QT dispersion on a standard electrocardiogram (ECG) is a measure
      of repolarization inhomogeneity, but its prognostic meaning in myocardial
      infarction (MI) survivors is unclear, especially in patients with left
      ventricular dysfunction. RR interval has been shown to predict mortality in post
      MI patients, but its prognostic power has not been compared with other
      noninvasive risk factors. METHODS: Retrospective cohort study. Ninety patients
      were identified, from a series of 547 consecutive postinfarction patients
      admitted to our institution for phase II cardiac rehabilitation, as having a LVEF
      of <0.40 at two-dimensional echocardiography (mean LVEF 0.35+/-0.04; range 0.20
      0.39). QT dispersion and RR interval were analyzed on the admission 12-lead
      electrocardiogram, 20+/-10 (range 8-45) days after MI, using specially designed
      software. Additional risk markers were collected from clinical variables, signal
      averaged ECG and Holter recording. RESULTS: During 24+/-18 (range 1-63) months of
      follow-up, 10 of 90 patients (11%) died, all from cardiac causes, and there were
      18 late arrhythmic events, defined as sudden death or the occurrence of a
      sustained ventricular arrhythmia > or =5 days after the index MI. QT interval and
      dispersion were not significantly prolonged in patients who died compared to
      survivors and not significantly different between patients with and without
      arrhythmic events. Mean RR interval from standard ECG was significantly shorter
      in patients with both cardiac death (682+/-99 vs. 811+/-134 ms; P=0.004) and
      arrhythmic events (720+/-100 vs. 818+/-139 ms; P=0.006). A Cox proportional
      hazards model identified RR interval from standard ECG (P<0.001) and a history of
      more than one MI (P=0.002) as significant predictors of cardiac death independent
      of thrombolytic therapy, LVEF, filtered QRS complex duration at signal-averaged
      ECG, mean RR and its standard deviation at 24-h Holter monitoring. CONCLUSIONS:
      Measurement of QT interval and dispersion 3 weeks after MI has no prognostic
      power in patients with LV dysfunction after a recent MI. RR interval on standard
      12-lead ECG is as good a prognostic indicator as other, more expensive,
      noninvasive markers. These findings may be relevant in this era of limited health
      care resources.

PMID- 10077406
TI  - Development of atherosclerosis over a 25 year period: an epidemiological autopsy
      study in males of 11 towns.
AB  - We conducted an analysis of the data from two epidemiological autopsy studies of
      atherosclerosis in men aged 20-59 years in 1963-66 (the first study, 7470 cases)
      and in 1985-88 (the second study, 9600 cases). The investigations were performed
      in accordance with a special program of the World Health Organization in 11 town
      populations: Ashkhabad (Turkmenistan), Bishkek (Kirgizstan), Irkutsk and Yakutsk
      (Russia), Malmo (Sweden), Prague (Czech Republic), Riga (Latvia), Tallinn and
      Tartu (Estonia), and Kharkov and Yalta (Ukraine). Native and non-native
      populations were studied separately in Ashkhabad, Bishkek, and Yakutsk.
      Atherosclerosis was studied by the visual morphometrical method in the descending
      thoracic aorta, abdominal aorta and three main coronary arteries. In each vessel
      the prevalence and extent (percent of intimal surface) of fatty streaks, fibrous
      plaques, complicated, calcified and also raised lesions (all lesions except fatty
      streaks) were determined. Coronary stenosis was estimated in arteries as narrowed
      by more than 50%. Accelerated development of coronary atherosclerosis, especially
      in the 40-59 year age group, was noted in the second study in the male
      populations of most towns except Prague and Malmo. In Prague the extent of raised
      lesions in coronary arteries was practically the same in both studies, in Malmo
      it decreased in the second study. Aortic atherosclerosis also accelerated the
      rate of progression in all towns except Prague, where significant differences
      were not observed between the studies. Accelerated development of atherosclerosis
      in male populations from towns of Asia was combined with an increase of fatty
      streaks in all vessels, while in European populations it was not so obvious. In
      the native populations of Ashkhabad, Bishkek and Yakutsk, atherosclerosis was
      much less than in non-natives in both studies. In natives of these towns,
      accelerated development of atherosclerosis begins only from 40 years, in non
      natives from 30. For the second study, there was typically an increase of the
      prevalence and extent of calcified lesions that were combined with an increased
      prevalence of coronary stenosis in all towns. The average percentage of stenosis
      in the coronary left anterior descending artery for men of 40-59 years of age was
      12% in the first study and 24.9% in the second; for the coronary right artery,
      7.4 and 13.8%, respectively. In accordance with findings of more severe
      atherosclerosis in males in most towns in the second study, there was an increase
      in the frequency of death from coronary heart disease in the second study in
      these towns. The data of this study indicate that the development of
      atherosclerosis in human populations may change very much in the course of the
      life of one generation.

PMID- 10077407
TI  - Non-invasive evaluation of coronary reserve. Assessment of coronary reserve in
      patients with coronary artery disease by transesophageal-Doppler
      echocardiography.
AB  - We assessed coronary flow reserve using transesophageal Doppler echocardiography
      in patients with coronary artery disease. The study included 33 coronary artery
      disease patients who were undergoing coronary arteriography. The blood flow
      velocities of the left anterior descending artery before and after intravenous
      infusion (0.56 mg/min for 4 min) of dipyridamole were recorded using
      transesophageal Doppler echocardiography. Fourteen normal healthy individuals,
      matched for age, served as a control group. The index of coronary flow reserve,
      i.e. the ratio of dipyridamole to baseline maximum diastolic velocity, was
      calculated. Maximal coronary flow reserve in coronary artery disease patients was
      significantly lower than in the control group (1.4+/-0.2 vs. 2.8+/-0.3, P<0.001).
      The coronary artery disease patients were classified into three groups: Group A
      included 10 patients with <50% left anterior descending artery stenosis; Group B
      included seven patients with 50-69% left anterior descending artery stenosis; 16
      patients with >70% left anterior descending artery stenosis constituted Group C.
      The maximum coronary flow reserve was significantly different for A vs. B and A
      vs. C. (A, 1.77+/-0.18; B, 1.51+/-0.1; C, 1.28+/-0.24). A strong and significant
      correlation was found between the maximum coronary flow reserve and the degree of
      proximal left anterior descending artery stenosis (r=0.78, P<0.001). Coronary
      artery disease patients without left anterior descending artery stenosis on the
      arteriogram exhibited lower maximum coronary flow reserve compared to the control
      subjects (1.78+/-0.19 vs. 2.8+/-0.3, P=0.000).

PMID- 10077408
TI  - Extracellular matrix structure after heart transplantation.
AB  - Following heart transplantation remodeling of the donor heart causes changes in
      the extracellular myocardial matrix. We investigated 20 right ventricular
      endomyocardial biopsies taken 17+/-4 days (group I, n=9) and 63+/-13 days (group
      II, n=11) after heart transplantation from 16 patients transplanted for end-stage
      cardiomyopathy (15 dilated/1 ischemic). Immunohistochemical staining for collagen
      I, collagen III, collagen IV, and fibronectin was used. Evaluation was performed
      at a magnification of 400x using a computer-assisted image analyzing system
      measuring the relative area stained by the immunoperoxidase method, the number of
      cells in the given area, and the total area. Collagen I per cell was 13.9+/-5.9
      microm2 in group I and increased significantly 66+/-13 days after heart
      transplantation in the perimysium around the myocardial cells as well as in the
      endocardium to 49.9+/-15.1 microm2 (P<0.05). No quantitative change in collagen
      III was noted (75.7+/-12.4 versus 75.5+/-16.0 microm2 n.s.). Collagen IV was
      found in the perimysial, in the capillary bed and in the vascular network.
      Significant quantitative change in the amount of collagen IV was not found
      (64.1+/-12.6 versus 61.0+/-8.9 microm2). Fibronectin was found in the entire
      perimysial extracellular matrix and in the endocardium in relationship with
      collagen I and III. An increased amount of fibronectin from 87.09+/-9.9 microm2
      (group I) to 140.8+/-17.9 microm2 (group II, P<0.05) was found. The cell area and
      cell diameters were not significantly different (group I; cell area 772+/-227
      microm2, diameter 31.3 microm; group II; cell area 776+/-224 microm2, diameter
      31.4 microm). It is concluded that remodeling of the donor heart after
      transplantation is characterized by a specific increase in collagen I and
      fibronectin, whereas a change in other collagen subtypes was not observed.

PMID- 10077409
TI  - Unusual coronary artery dissection during percutaneous transluminal coronary
      angioplasty: report of a case.

PMID- 10077410
TI  - Electrocardiographic diagnosis of right ventricular infarction in the presence of
      left ventricular posterior infarction.
AB  - Conventional criteria of ST segment elevation in right sided chest leads or loss
      of initial 'r' wave in leads V3R or V4R have low sensitivity and specificity in
      diagnosing right ventricular involvement in the presence of left ventricular
      posterior infarction. Slurring of R wave either in right sided chest leads or in
      lead aVR can diagnose right ventricular involvement in such a setting with a
      sensitivity of 70% and specificity of 94%.

PMID- 10077411
TI  - Human rabies prevention--United States, 1999. Recommendations of the Advisory
      Committee on Immunization Practices (ACIP).
AB  - These revised recommendations of the Advisory Committee on Immunization Practices
      update the previous recommendations on rabies prevention (MMWR 1991;40[No.RR-3]:1
      14) to reflect the current status of rabies and antirabies biologics in the
      United States. This report includes new information about a human rabies vaccine
      approved for U.S. use in 1997, recommendations regarding exposure to bats,
      recommendations regarding an observation period for domestic ferrets, and changes
      in the local administration of rabies immune globulin.

PMID- 10077412
TI  - Reducing hypertension-associated cardiorenal risk: the role of heart rate, left
      ventricular hypertrophy regression, and renoprotection.

PMID- 10077413
TI  - The physiological determinants and risk correlations of elevated heart rate.
AB  - A number of studies have shown that fast heart rate is associated with high blood
      pressure and metabolic disturbances, and that it is a strong precursor of
      hypertension, atherosclerosis, and cardiovascular events. Subjects with
      tachycardia often also exhibit increased plasma insulin, overweight, and higher
      hematocrit. These relationships have been observed also in the elderly and among
      hypertensive individuals and have held true after controlling for smoking,
      alcohol intake, and physical activity habits. In three different populations
      studied with a mixture analysis we demonstrated that the heart rate-blood
      pressure association was mostly explained by a subpopulation of subjects with
      high heart rates who had higher levels of blood pressure, total cholesterol,
      triglycerides, postload glucose, and plasma insulin. The clustering of these risk
      factors may explain why cardiovascular morbidity is higher in individuals with
      fast heart rates. Sympathetic overactivity seems to be responsible for both the
      increase in heart rate and blood pressure, and for the metabolic abnormalities.
      In addition to being a marker of sympathetic overactivity, tachycardia seems to
      have a direct action in the induction of risk. Studies in cholesterol-fed monkeys
      have shown that the reduction of heart rate could retard the development of
      coronary atherosclerosis. Furthermore, fast heart rate increases the pulsatile
      nature of the arterial blood flow and increases arterial wall stress.
      Antihypertensive drugs that lower the heart rate seem to have a good potential
      for prolonging life expectancy in humans.

PMID- 10077414
TI  - Effects of antihypertensive single-drug therapy on heart rate. Department of
      Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
AB  - Heart rate increasingly is being recognized either as an independent risk factor
      for a wide variety of cardiovascular disorders or as a surrogate marker for them.
      We analyzed the changes in heart rate associated with antihypertensive therapy
      with six drugs and placebo from the VA Cooperative Study on Single-Drug Therapy.
      These results were published previously (American Journal of Hypertension
      1998;11:597-601). This paper provides a summary of the earlier publication with
      the addition of three figures not previously published. Atenolol had the greatest
      effect on heart rate reduction, followed by clonidine and diltiazem-SR.
      Hydrochlorothiazide and captopril were associated with small reductions in heart
      rate over time, whereas prazosin increased heart rate. Patients whose blood
      pressure was controlled by placebo had a 3.1 beats/min reduction of heart rate at
      2 years. When the baseline heart rate was 65 beats/min or less, all drugs
      increased the heart rate except for atenolol, which further reduced it. Although
      it is clear that each of the six drugs used in our study had a different effect
      on heart rate, we cannot state that drug-induced reduction in heart rate per se
      confers a decrease in cardiovascular risk.

PMID- 10077415
TI  - Clinical trials of single-drug therapy for the cardiac effects of hypertension.
AB  - Much has been learned in epidemiologic studies and clinical trials about the
      relationships between hypertension and cardiac anatomic and functional responses,
      as well as the effects of antihypertensive treatment on those responses. The
      results of recent multicenter trials have supported initial concerns that not all
      drugs effective for blood pressure reduction are effective for reduction of LV
      mass and regression of LVH. However, recent trials of single-drug therapy suggest
      that those agents initially believed to be ineffective for LV mass reduction
      (principally diuretics and beta-blockers), on the basis of pathophysiologic
      theory and inadequate clinical trials, may in fact be quite effective for LVH
      regression, as well as for improving cardiac outcomes. Additionally, fears
      concerning the adverse effects of LV mass reduction on systolic and diastolic LV
      function have not been justified by the results of clinical trials. In
      conclusion, the often-assumed lack of efficacy of diuretics and beta-blockers for
      the reduction of LV mass can no longer be used as a reason to disregard the
      longstanding recommendations of the Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of Hypertension supporting the use of
      diuretics and beta-blockers as the initial drug treatment of hypertension.

PMID- 10077416
TI  - Renoprotective effects of antihypertensive drugs.
AB  - Regardless of the specific antihypertensive agent used, the most important aspect
      of the management of the patient with coexistent hypertension and renal disease
      is adequate control of the blood pressure. The current JNC VI recommendation is
      for a reduction to a target blood pressure of 130/85 mm Hg, or to a lower value
      of 125/75 in patients with greater than 1 g proteinuria per day. Impaired renal
      sodium excretion leading to extracellular fluid volume (ECFV) expansion is the
      most clinically important mechanism leading to renal parenchymal hypertension.
      Sodium restriction and loop diuretics constitute the cornerstone of effective
      antihypertensive therapy. Control of blood pressure in patients with chronic
      renal disease may be difficult without measures that address ECFV. JNC VI
      recommends the use of angiotensin converting enzyme (ACE) inhibitors in patients
      with hypertension and chronic renal disease to control hypertension and to slow
      progressive renal failure. ACE inhibitors have been found by clinical trials to
      be useful agents in the settings of established insulin-dependent diabetes
      mellitus (IDDM) nephropathy, non-insulin-dependent diabetes mellitus (NIDDM)
      nephropathy, IDDM patients with normal blood pressures and microalbuminuria,
      NIDDM patients with microalbuminuria and normal renal function, and a variety of
      nondiabetic renal diseases, especially in the setting of significant proteinuria.
      Calcium antagonists are effective for treating hypertensive patients with chronic
      renal impairment but have not been studied as intensively as ACE inhibitors with
      regard to their ability to slow the progression of renal insufficiency
      independently of their blood-pressure-lowering effects. The initial results for
      calcium antagonists and for combination calcium antagonist-ACE inhibitor therapy
      have been promising. The angiotensin II antagonists have theoretical advantages
      for use in renal impairment, and seem to have similar renal hemodynamic and
      antiproteinuric effects to ACE inhibitors, but further clinical study is needed.

PMID- 10077417
TI  - Identification of CD4+ and CD8+ T cell subsets and B cells in the brain of dogs
      with spontaneous acute, subacute-, and chronic-demyelinating distemper
      encephalitis.
AB  - CD4 and CD8 antigen expression of T cells as well as B cell and canine distemper
      virus (CDV) antigen distribution were immunohistologically examined in the
      cerebellum of dogs with spontaneous distemper encephalitis. Cellular and viral
      antigen expression were evaluated at intralesional and extralesional sites and in
      the perivascular space. Histologically, acute and subacute non-inflammatory
      encephalitis and subacute inflammatory and chronic plaques were distinguished.
      Demyelination was a feature of all subacute and chronic lesions, although the
      majority of plaques exhibited no or only a low level of active demyelination as
      demonstrated by single macrophages with luxol fast blue positive material in
      their cytoplasm. CDV antigen expression, observed in all distemper brains, was
      reduced in chronic plaques. CD4+, CD8+, and B cells were absent in controls and
      in some brains with acute encephalitis. A mild infiltration of CD8+ cells was
      noticed in the neuropil of the remaining brains with acute and all brains with
      subacute non-inflammatory encephalitis. Single CD4+ cells were found in two
      brains with acute and in all brains with subacute non-inflammatory encephalitis.
      Numerous CD8+ and CD4+ cells and few B cells, with a preponderance of CD8+ cells,
      were detected in subacute inflammatory and chronic lesions. In contrast, in
      perivascular infiltrates (PVI) of subacute and chronic lesions a dominance of
      CD4+ cells was detected. The dominating CD8+ cells in acute and subacute non
      inflammatory encephalitis might be involved in viral clearance or contribute as
      antibody-independent cytotoxic T cells to early lesion development. In subacute
      inflammatory and chronic lesions CD8+ cells may function as cytotoxic effector
      cells and CD4+ cells by initiating a delayed-type hypersensitivity reaction. The
      simultaneous occurrence of perivascular B and CD4+ cells indicated that an
      antibody-mediated cytotoxicity could synergistically enhance demyelination.
      Summarized, temporal and spatial distribution of CD4+, CD8+ and B cells and virus
      antigen in early and late lesions support the hypothesis of a heterogeneous in
      part immune-mediated plaque pathogenesis in distemper demyelination.

PMID- 10077418
TI  - Analysis of the humoral immune response against total and recombinant antigens of
      Leishmania infantum: correlation with disease progression in canine experimental
      leishmaniasis.
AB  - Leishmaniasis by Leishmania infantum in the Mediterranean Basin constitutes an
      important problem in both human and veterinary medicine. Based in both the
      importance of canids as reservoirs for the human disease and the fact that the
      canine disease may be an excellent model for the human condition, the present
      work has been conducted to analyze clinical and immune mechanisms associated with
      canine experimental leishmaniasis. Six-month-old mixed-breed dogs were
      intravenously infected with L. infantum promastigotes and the infection course
      was monitored along a 343 days-period. On day 75 post-infection (p.i.),
      amastigotes were observed in the lymph nodes of all dogs. The analysis of the
      humoral response against total L. infantum antigens by both ELISA and Western
      blotting evidenced a correlation between the levels of IgG isotypes (IgG1 and
      IgG2) and disease progression. It was observed that in those animals showing
      either a regressive or an oligosymptomatic form of the disease, the anti
      Leishmania IgG1 antibodies were undetectable whereas those animals developing
      active disease showed high levels of anti-Leishmania IgG1 antibodies.
      Additionally, the time-course of antibody production against L. infantum
      recombinant antigens in the experimentally infected dogs has been analyzed. The
      present data suggest that reactivity against the heat-shock protein 70 (HSP70)
      may be used as diagnostic marker of early steps of infection, and that the
      appearance of anti-histone antibodies is associated with progression of infection
      to disease status.

PMID- 10077419
TI  - Reduction of CD4+ and CD8+ T lymphocytes during febrile periods in horses
      experimentally infected with equine infectious anemia virus.
AB  - Three horses were experimentally infected with equine infectious anemia virus
      (EIAV). All horses were febrile after inoculation with EIAV and then developed
      chronic symptoms with intermittent fever. The febrile period was characterized by
      a rise in body temperature with reduced PBL and erythrocyte counts. Flow
      cytometric analysis showed that the reduced number of lymphocytes was due to
      significant decreases in CD4+ and CD8+ T cells in the absence of any change in B
      cell number. At the end of the febrile period the body temperature began to
      recover and numbers of CD4+ and CD8+ T cells showed a tendency to increase. For
      CD8+ T cells, this increase continued for several days after the febrile period.
      B cell number also significantly increased after the febrile period in two out of
      three horses. The decrease of CD8+ T cells was greater than that of CD4+ T cells.
      Although the PBL numbers and the CD4/CD8 ratio returned to the level of the
      preinoculation period, erythrocyte numbers decreased as the body temperature
      normalized after each intermittent fever. These results suggest that the
      recurring cycle of fever accompanied with viremia is caused by a reciprocal
      relationship between EIAV replication and the host immune response. Furthermore,
      we demonstrate that the lymphocytic response mitigates fever and viremia in EIAV
      infection despite the absence of virus neutralizing antibody.

PMID- 10077420
TI  - Granulocyte function in dogs experimentally infected with a Swedish granulocytic
      Ehrlichia species.
AB  - Granulocyte function was studied in six dogs inoculated with a Swedish
      granulocytic Ehrlichia species and in four control dogs. Whole blood
      chemiluminescence (CL) was enhanced in the dogs with granulocytic ehrlichiosis.
      Both CL after stimulation with zymosan and spontaneous CL was significantly
      increased at peak of infection compared with pre-infection levels. Ingestion of
      FITC-labelled serum-opsonized yeast cells was high and stable in both groups. The
      ingestion was lower when the yeast cells were opsonized with anti-yeast IgG.
      However, there was no difference between groups. The labelling intensity of anti
      human CD11b, CD18 and CD32 mAb on the granulocytes in dogs with ehrlichiosis was
      similar to that in control dogs. The opsonic activity in serum collected at the
      peak of infection was not different from serum drawn prior to inoculation.
      Opsonic activity was investigated both by yeast cell ingestion and by
      chemiluminescence after stimulation with zymosan. The serum from infected dogs
      enhanced the respiratory burst without stimulation with zymosan of leukocytes
      from healthy dogs. This suggests that serum at the peak of infection contains
      granulocyte activators. In this study we found normal phagocytosis together with
      evidence of enhanced oxidative metabolism in the granulocytes from dogs with
      granulocytic ehrlichiosis.

PMID- 10077421
TI  - Effects of mild stress on the immune response against pseudorabies virus in mice.
AB  - Stress is a recognised problem in intensive pig husbandry, which might lead to
      changes in immune reactivity. To study the effect of stress on the development of
      an anti-viral immune response, we used a murine model in which mice were
      immunized with an attenuated strain of pseudorabies virus (PRV). The effect of
      two stress treatments, both relevant to intensive pig husbandry, on the
      development of the specific immune response against PRV was investigated. The
      stress treatments consisted of restraint, social isolation, and transport and
      they differed in predictability. The specific immune response against PRV, which
      developed in the draining lymph nodes, was measured by a lymphocyte proliferation
      assay and cytokine production assays. Our results showed that the unpredictable
      stress treatment had no effect on the development of the immune response against
      PRV in mice, whereas the predictable stress treatment actually hastened the
      immune response.

PMID- 10077422
TI  - Primary and anamnestic responses of bovine bronchoalveolar and peripheral blood
      lymphocyte subsets to aerosolized Pasteurella haemolytica A1.
AB  - Site-specific responses of bronchoalveolar and peripheral blood lymphocyte
      subsets were compared during primary and anamnestic immune responses against live
      Pasteurella haemolytica A1 (Ph1). Eight 1-year old calves were sequentially
      exposed intrabronchially with aerosolized Ph1 on days 0, 14, and 21, and two
      calves were sham exposed. Bronchoalveolar and peripheral blood lymphocytes were
      analyzed before each Ph1 exposure, and on days 3 and 7 post exposure using single
      and two-color flow cytometry to identify CD2+, CD4+, CD8+, CD21+, CD45R+, CD25+
      and gammadelta lymphocyte subsets. Significant differences (p < 0.05) in
      bronchoalveolar and peripheral blood lymphocyte subsets were observed before Ph1
      exposure. Subsequent aerosol exposures, resulted in significant (p < 0.05)
      changes in bronchoalveolar lymphocyte subsets and the CD4:CD8 bronchoalveolar
      lymphocyte ratio, but concomitant changes were not observed in peripheral blood
      lymphocytes. Expression of CD2, CD4 and CD8 lymphocyte differentiation antigens
      was consistently lower and more heterogeneous on bronchoalveolar lymphocytes.
      Differential analysis of bronchoalveolar leukocytes revealed a significant
      increase in bronchoalveolar lymphocytes and neutrophils during anamnestic
      responses.

PMID- 10077423
TI  - Oxidative responses in ferret macrophages.
AB  - Although the basic function of T and B lymphocytes in ferrets has been known for
      some time, the function of mononuclear phagocytes has not been described in this
      species. The present study has characterised basic oxidative responses in ferret
      macrophages, and has investigated the effects of endogenous and exogenous
      modulators of macrophage function on oxidative capacity in vitro. Macrophages
      derived from the blood or lungs of ferrets were shown capable of generating the
      reactive oxygen intermediate (ROI) molecules superoxide and hydrogen peroxide,
      and secreting a lysosomal enzyme (acid phosphatase), in response to appropriate
      stimuli. A T cell supernatant (derived from mitogen-stimulated peripheral blood
      lymphocytes) was able to activate both blood- and lung-derived macrophages for
      enhanced ROI production, while specific ROI inhibitors (superoxide dismutase and
      catalase) were able to partially ablate ROI activity. The accumulation of nitrite
      in culture supernatants, as an indicator for the production of reactive nitrogen
      intermediates, could not be demonstrated by ferret macrophages derived from
      either tissue source. In contrast to the enhancing effects of TCS on the
      oxidative function of blood-derived macrophages, exposure to bacterial LPS caused
      marked suppression of ROI and lysosomal enzyme production by these cells.
      Finally, the generation of superoxide anion, following phagocytosis of live or
      heat-killed Mycobacterium bovis or zymosan, indicated that ROI production in
      response to phagocytic stimulation was relatively weak in ferret blood-derived
      macrophages. These results are discussed in relation to the study of immune
      function in a novel species, and with particular reference to research into
      tuberculosis (Tb), since ferrets are important wildlife vectors of bovine Tb in
      New Zealand.

PMID- 10077424
TI  - Secretion of Salmonella-specific antibodies in the oviducts of hens
      experimentally infected with Salmonella enteritidis.
AB  - The production and secretion of Salmonella enteritidis whole cell antigen
      specific antibodies in the oviducts and in the serum of laying hens
      experimentally infected with Salmonella enteritidis, was analyzed by ELISA. The
      dynamics of the antibody levels in the oviducts were identical to that in the
      serum. Subclasses of antibodies (IgA, IgG, and IgM) in the infected hens were
      found to increase significantly (p < 0.01) compared to those in the control
      uninfected hens throughout the experiment. IgG and IgM levels in both oviducts
      and in sera reached to a peak by 14 days post-inoculation, and remained elevated
      throughout. The secretion of IgA seemed to be transient since the IgA levels
      increased to a peak 7 days after both primary and secondary inoculations, and
      declined rapidly. The elevated levels of antibodies were followed by partial
      clearance of Salmonella organisms from the oviducts. The present results indicate
      a significant local immune reaction against the Salmonella infection and suggest
      an association of the local antibodies with the clearance of Salmonella from the
      oviducts at least partially.

PMID- 10077425
TI  - Experimental infection of calves with bovine leukemia virus (BLV): an applicable
      model of a retroviral infection.
AB  - An experimental model of chronic infection with bovine leukemia virus (BLV) was
      established in young calves within a relatively short time. In the sera of all
      infected calves, precipitating antibodies were detected within 5 weeks after
      infection but upon disease progression pattern of cellular profiles varied. Three
      calves exhibited transient lymphocytosis 3-5 weeks after infection, two became
      persistent lymphocytotic (PL+) by that time and one stayed non-lymphocytotic (PL
      ) for 11 weeks and became PL+ after 4.5 months. Eventually all infected calves
      became PL+ by the end of the experiment, 6-12 months after infection. Increase of
      total counts of peripheral blood mononuclear cells (PBMC) related to polyclonal
      expansion of B-cells. The latter was assessed in all infected calves where the
      expansion of CD5-bearing cells (B+ CD5+) correlated with increase or decrease of
      total PBMC counts. Other cell populations such as CD4 and CD8 were also affected.
      Percentages decreased by 5 weeks after experimental infection to about half their
      original values though actual cell numbers stayed relatively stable. The
      experimental model we established compared well with field cases of naturally BLV
      infected cattle and thus permitted the investigation of the disease at early
      stages of infection.

PMID- 10077426
TI  - Action of a new mammalian DNA polymerase inhibitor,
      sulfoquinovosyldiacylglycerol.
AB  - We found and previously reported a new mammalian DNA polymerase inhibitor from a
      sea alga, Gigartina tenella, (Ohta K., et al., Chem. Pharm. Bull., 46, 684-686,
      1998). It was a new sulfolipid compound that belonged in the class of
      sulfoquinovosyldiacylglycerol. The biochemical properties have been investigated
      here. The compound, temporarily designated KM043, potently inhibited the
      activities of mammalian DNA polymerase alpha(pol. alpha) and DNA polymerase
      beta(pol. beta) and terminal deoxynucleotidyl transferase (TdT), and moderately,
      human immunodeficiency virus reverse transcriptase (HIV-RT). KM043 dose
      dependently inhibited their activities, and each of their IC50 values was 0.25
      microM for pol. alpha, 0.38 microM for TdT, 3.6 microM for pol. beta, or 11.2
      microM for HIV-RT, and almost complete inhibition of each was achieved at 1.0 to
      2.0 microM for pol. alpha and TdT, 7.5 microM for pol. beta and about 30 microM
      for HIV-RT. However, the compound did not influence the activities of prokaryotic
      DNA polymerases such as E. coli DNA polymerase I, and DNA metabolic enzymes like
      DNase 1. Inhibition of pol. alpha or beta by KM043 was non-competitive with both
      the DNA template and the substrate deoxythymidine 5'-triphosphate (dTTP). KM043
      was weakly cytotoxic to cultured HeLa-S3 cells, and the IC50 value was 80 microM.
      KM043 could synergistically enhance the cytocidal effect of an anti-cancer
      chemotherapy agent, bleomycin. In the presence of 50 microM KM043, the effect
      ratio of (bleomycin plus KM043)/(bleomysin only) decreased from 0.76 to 0.22.

PMID- 10077427
TI  - Suppression and enhancement of the Freund's incomplete adjuvant-induced writhing
      reaction by sodium ascorbate in mice.
AB  - We noticed that an intraperitoneal injection of Freund's incomplete adjuvant
      (FIA) into mice could stimulate the induction of a writhing reaction. The FIA
      emulsion-induced writhing reaction was found to be remarkably inhibited by
      preadministration of oral indomethacin, a non-steroidal anti-inflammatory and
      analgesic drug. The induction of the writhing reaction was also inhibited by
      intravenous preadministration of sodium ascorbate (SAs) in saline. In the
      experiments where SAs was added to FIA, it was demonstrated that SAs had dual
      activity of suppression and enhancement. At lower concentrations SAs functioned
      as a suppressor of the writhing reaction, while at concentrations higher than
      about 1 mg/50 microl/mouse it acted as an enhancer of the reaction. Furthermore,
      this writhing reaction induced by FIA+SAs emulsion was also inhibited by
      preadministraion of SAs itself as well as indomethacin. These results suggested
      that the mechanism of the writhing reaction induced by FIA was concerned with the
      production of prostaglandins (PGs), and SAs might be involved in regulation of
      the writhing reaction. In this paper, we propose a mouse writhing model induced
      by FIA or FIA+SAs emulsion as a novel pain model useful for assessment of
      analgesic and anti-inflammatory agents.

PMID- 10077428
TI  - Phosphorylation of proteins in the stem section of etiolated rice seedling
      irradiated with red light.
AB  - The molecular mechanism of light signal perception was analyzed using stem
      sections of etiolated rice (Oryza sativa L.) seedlings irradiated with red light
      from a fluorescent lamp. The membrane and cytosol fractions were labeled by 40 nM
      [gamma-32P]ATP for 10 s at 0 degrees C and proteins were separated by two
      dimensional polyacrylamide gel electrophoresis. Phosphorylation of three proteins
      with molecular weights of 16, 17 and 18 kDa in the rice increased with the
      intensity of red light irradiation (50 micromol/m2/s) for 16 min. Most of the
      phosphorylation activity was present in the cytosol fraction. The three proteins
      cross-reacted with the anti-nucleoside diphosphate (NDP) kinase antibody.
      Phosphorylation of these proteins was correlated with changes in the activity of
      NDP kinase. These proteins phosphorylated histone III-S, a substrate for
      measuring the protein kinase activity. By phospho-amino acid analysis,
      phosphoserine was found present in the phosphorylated proteins. These rapidly
      phosphorylated proteins would thus appear to have the features of NDP kinase.

PMID- 10077429
TI  - Effect of IS-741 on cell adhesion between human umbilical vein endothelial cells
      and HL-60 cells.
AB  - The effect of IS-741 (N-[(2-ethylsulfonylamino)-5-trifluoromethyl-3-pyridyl]
      cyclohexanecarboxamide monohydrate) on a model for pancreatitis has been
      previously reported. Recent patho-histological observations of remedial tests
      using rats found that the IS-741 administered group showed a low degree of tissue
      infiltration by inflammatory cells (polymorphonuclear leukocytes). We therefore
      examined cell adhesion, which is the first step in tissue infiltration by
      activated neutrophils, and investigated the effect of IS-741 on cell adhesion
      between human umbilical vein endothelial cells (HUVEC) and human promyelo
      leukemia cell line (HL-60) cells during lipopolysaccharide stimulation in vitro.
      IS-741 significantly inhibited the adhesion of HL-60 cells to HUVEC. Further
      investigation of IS-741 on individual cells revealed that IS-741 mainly affected
      HL-60 cells. Investigation of the inhibitory effect of IS-741 at the molecular
      level (targeting adhesion molecules) also revealed that IS-741 had no effect on
      the appearance of endothelial leukocyte adhesion molecule-1 (ELAM-1),
      intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1
      (VCAM-1) on HUVEC, which supports the theory that IS-741 is mainly effective on
      HL-60 cells, even at the molecular level. However, the inhibition of adhesion was
      noticed in experiments in which an anti-ICAM-1 or anti-VCAM-1 antibody was added
      to the adhesion test system. Therefore, IS-741 is likely to affect adhesion
      molecules which belong to the beta1 or beta2 integrin family.

PMID- 10077430
TI  - Metallothionein induction in rat liver by dietary restriction or exercise and
      reduction of exercise-induced hepatic lipid peroxidation.
AB  - Metallothioneins (MTs) occur throughout the animal kingdom and they are induced
      in vivo by metals, hormones, cytotoxic agents, and some kind of stress. It is
      well known that various stresses such as starvation and immobilization can induce
      MT synthesis in animal tissues, but the influence of dietary restriction is
      unknown. The MT levels in the liver increased by food-deprivation and then
      decreased by refeeding, and a long period of starvation down-alters hepatic MT
      levels. When the stress is intensified, the induced quantity of hepatic MT is
      reduced. It became clear that hepatic MT concentrations are controlled within a
      two fold limit when stressed by dietary restriction. MT was also induced in rat
      liver at recovery stage following an exhaustive running exercise, and thionein
      was synthesized first and then zinc bound to the protein. The half-life of
      hepatic MT induced by exercise (which is a nonmetallic inducer) was estimated at
      5.2 h. Preinduced MT markedly suppressed exercise-induced lipid peroxidation in
      rat liver.

PMID- 10077431
TI  - Evidence for the involvement of platelet-derived growth factor in the angiotensin
      II-induced growth of rat vascular smooth muscle cells.
AB  - This study examines the possible involvement of endogenous platelet-derived
      growth factor (PDGF) in the angiotensin II-induced growth of rat aortic smooth
      muscle cells. In quiescent confluent cells, anti-PDGF-AB neutralizing antibody
      inhibited angiotensin II-induced DNA synthesis and protein synthesis. PDGF-AA, 
      AB, and -BB produced concentration-dependent increases in DNA synthesis and
      protein synthesis. Genistein did not inhibit PDGF-AB-induced [3H]thymidine
      incorporation and [3H]leucine incorporation. PDGF-AB stimulated mitogen-activated
      protein (MAP) kinases, and PDGF-induced MAP kinase activation was inhibited by
      genistein. Angiotensin II induced PDGF-A chain messenger RNA expression, and
      genistein inhibited angiotensin-induced PDGF gene expression. These findings
      suggest that endogenous PDGF is, at least in part, involved in angiotensin II
      induced cell growth in rat vascular smooth muscle cells. It appears that
      genistein inhibits angiotensin II-induced DNA synthesis partly by inhibiting PDGF
      A gene expression.

PMID- 10077432
TI  - Identification of metabolites of NK-104, an HMG-CoA reductase inhibitor, in rat,
      rabbit and dog bile.
AB  - NK-104 is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase with a very potent lipid-lowering effect. Biotransformation profiles of
      NK-104 in bile from rat, rabbit and dog given an intravenous infusion of NK-104
      were investigated. Structural assignment was made by liquid chromatography (LC)
      mass spectrometry (MS)-MS and proton NMR analyses. The predominant component was
      intact NK-104 in all the animals. At least eight other metabolites were present
      in rat, four in rabbit, and 10 in dog. These bile metabolites were purified and
      isolated by preparative HPLC. Biotransformation pathways elucidated for NK-104
      were as follows: (a) lactonization ; (b) beta-oxidation of the side-chain; (c)
      hydroxylation of the quinoline ring; (d) conjugation with Beta-glucuronic acid
      and taurine. Beta-oxidative degradation of the side-chain in the case of other
      HMG-CoA reductase inhibitors is necessary for epimerization of the hydroxy group
      which has an R-configuration. However, M-16, glucuronide of the ketolactone
      derivative, was obtained as a key metabolite suggesting another beta-oxidation
      pathway for the side-chain.

PMID- 10077433
TI  - In vitro and in vivo vasodilatory activity of barnidipine and its enantiomers.
AB  - Barnidipine, (3'S)-1-benzyl-3-pyrrolidinyl methyl (4S)-2,6-dimethyl-4-(m
      nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylat e, is a dihydropyridine calcium
      antagonist with asymmetric carbons at the dihydropyridine C-4 and the pyrrolidine
      C-3' positions. In this study, the vasodilatory activity of barnidipine and its 3
      optical isomers were compared in vitro and in vivo to assess the steric effects
      of these asymmetric carbons. All these enantiomers produced concentration
      dependent relaxation on KCI (40 mM)-induced contractions in isolated guinea pig
      aorta with a potency order of barnidipine>(3'R,4R) approximately/=
      (3'R,4S)>(3'S,4R). The potency ratio between barnidipine and the (3'S,4R)
      enantiomer was 118. All enantiomers increased coronary blood flow after intra
      arterial administration to anesthetized coronary-perfused dogs. The potency order
      almost agreed with that obtained in vitro, although the potency ratio between
      barnidipine and the (3'S,4R) enantiomer was only 15. These 4 enantiomers showed
      stereoselectivity for time course changes as well. The onset and disappearance of
      blood flow increase after intracoronary administration of barnidipine were slower
      than those of other enantiomers. The duration for barnidipine was longer than
      those for other dihydropyridine calcium antagonists such as nifedipine or
      nitrendipine. The present study suggests stereoselectivity for the C-4
      dihydropyridine and to a lesser degree for the C-3' of pyrrolidine in an ester
      moiety. The steric effects of these carbons were observed not only in the potency
      of vasodilatory activity but also in its duration.

PMID- 10077434
TI  - Prolyl endopeptidase inhibitors from the underground part of Rhodiola sacra S. H.
      Fu.
AB  - Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme which plays a role in the
      metabolism of proline-containing neuropeptides, e.g., vasopressin, substance P
      and thyrotropin-releasing hormone (TRH), which have been suggested to be involved
      in learning and memory processes. In our systematic screening for PEP inhibitors
      from traditional Chinese medicines, we found that MeOH extract from the
      underground part of Rhodiola sacra S. H. Fu shows significant inhibitory activity
      against PEP from Flavobacterium meningosepticum. Examination of the constituents
      of the extract resulted in the isolation of nineteen known compounds, identified
      as hydroquinone (1), 4-hydroxybenzoic acid (2), caffeic acid (3), 4
      hydroxycinnamic acid (4), suberic acid (5), protocatechuic acid (6), gallic acid
      (7), (-)-epigallocatechin 3-O-gallate (8), 2-phenylethyl beta-D-glucopyranoside
      (9), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate
      (10), 2-phenylethyl alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (11),
      sacranoside A (12), beta-D-glucopyranosyl 4-hydroxybenzoate (13), rhodiocyanoside
      A (14), rhodiooctanoside (15), sarmentosin (16), heterodendrin (17), arbutin (18)
      and 4-O-(beta-D-glucopyranosyl)-gallic acid (19). Among these, 1, 2, 5, 8-10, 13,
      16, 18 and 19 have been isolated for the first time from R. sacra, among which 5,
      9, 10, 13, 16, 18 and 19 have been isolated from Rhodiola plants for the first
      time. On the PEP inhibition, seven compounds (6-8, 10, 12, 18, 19) showed
      inhibition with an 1C50 of 27.8, 487, 1.47, 0.437, 348, 391 and 215 microM,
      respectively. The kinetic study of these inhibitors indicated that they are
      noncompetitive inhibitors, except for 6 which is a competitive inhibitor.

PMID- 10077435
TI  - Beta-glucuronidase-inhibitory activity and hepatoprotective effect of Ganoderma
      lucidum.
AB  - To prove the relationship between the fluctuation in serum beta-glucuronidase
      level and hepatotoxicity, an inhibitor of beta-glucuronidase from G. lucidum was
      isolated and its hepatoprotective activity was investigated. The ether fraction
      of G. lucidum, which had potent beta-glucuronidase-inhibitory activity, protected
      against CCl4-induced liver injury. From this ether fraction, ganoderenic acid A,
      was isolated as the potent inhibitor of beta-glucuronidase. It had a potent
      hepatoprotective effect against CCl4-induced liver injury. These results suggest
      that the beta-glucuronidase seems to be closely related to liver injury, which
      could be prevented by beta-glucuronidase inhibitors.

PMID- 10077436
TI  - Pharmacological properties of traditional medicines. XXV. Effects of ephedrine,
      amygdalin, glycyrrhizin, gypsum and their combinations on body temperature and
      body fluid.
AB  - Effects of ephedrine, amygdalin, glycyrrhizin, gypsum and their combinations on
      body temperature and body fluid were studied in rats using the method developed
      in our previous reports. Ephedrine significantly increased respiratory
      evaporative water loss and heat loss in response to a marked elevation of body
      temperature. There was a small but significant increase in body temperature when
      amygdalin was orally given rats at a dose of 46.32 mg/kg. Glycyrrhizin and gypsum
      were unable to affect body temperature. However, gypsum was able to prevent the
      increased action of ephedrine on body temperature, amygdalin exhibited a
      preventive tendency to it, and glycyrrhizin did not affect it. The results are in
      good agreement with classical claims of Makyo-kanseki-to and the related crude
      drugs in traditional medicine. Moreover, a combination of the four components
      reproduced the effects of Makyo-kanseki-to on body temperature and body fluid.
      This report suggests that the co-administration of ephedrine and gypsum is
      physiologically more desirable than ephedrine alone for dry-type asthmatic
      patients with a fever. Also, it experimentally supports the clinical efficacy of
      Makyo-kanseki-to.

PMID- 10077437
TI  - Prodrug for bioreductive activation-independent delivery of menahydroquinone-4:
      human liver enzymatic activation and its action in warfarin-poisoned human liver.
AB  - The N,N-dimethylglycine esters of menahydroquinone-4 (1-mono, 1; 4-mono, 2; 1,4
      bis, 3) were established in previous reports as prodrugs that could achieve the
      systemic bioreductive activation-independent delivery of menahydroquinone-4
      (MKH), the active form of menaquinone-4 (MK-4), in rat. The present study was
      undertaken to investigate if the prodrugs could undergo cleavage to parent drug
      (MKH) by a human tissues enzyme catalyzed hydrolytic pathway, the mechanism of
      the prodrugs for vitamin K-dependent carboxylation in human liver and their
      action in the warfarin poisoned human liver. The hydrolysis of the esters was
      shown to be catalyzed by esterases located in human liver but not in human
      plasma. The susceptibility of the esters to undergo human liver esterase
      hydrolysis was affected by the esterified position: 1>2>3. By using a human liver
      microsomal test system, the stimulation of vitamin K-dependent carboxylation with
      the prodrugs was determined. The prodrug could stimulate the carboxylation
      activity in the absence of dithiothreitol, an artificial activator of the
      reductive activation pathway of MK-4. The carboxylation activity of the prodrug
      was strongly inhibited in the presence of eserine, an esterase inhibitor. The
      prodrug could also stimulate the carboxylase under warfarin-poisoned conditions,
      where the vitamin K cycle was strongly inhibited. The results confirmed that the
      prodrug could generate MKH in human liver (active site), and that the resultant
      MKH could act as a cofactor for the carboxylase without reductive activation
      processes of MK-4 to MKH. Such bioreductive activation-independent vitamin K
      dependent carboxylation characteristic of the prodrug leads to enhanced
      pharmacological efficacy in the treatment of hypoprothrombinaemia induced in
      patients with coumarin and cephalosporin therapies.

PMID- 10077438
TI  - Biodisposition characteristics of N-succinyl-chitosan and glycol-chitosan in
      normal and tumor-bearing mice.
AB  - Two water-soluble chitosan derivatives, N-succinyl-chitosan (Suc-chi; average MW
      3x10(5)) and glycol-chitosan (Gly-chi; average MW 1.5x10(5)), were examined
      concerning their biodisposition characteristics in order to evaluate their
      possible use as water-soluble drug carriers. Their body distribution and urinary
      excretion were investigated by i.v. administration of FITC-labeled Suc-chi (FTC
      Suc-chi) and FITC-labeled Gly-chi (FTC-Gly-chi) to normal and Sarcoma 180 solid
      tumor-bearing mice. In normal mice, both polymers showed good retention in blood
      circulation; especially, FTC-Suc-chi exhibited a long half-life of 51 h, and its
      distribution to other tissues was very small. FTC-Gly-chi was distributed into
      the kidney to a relatively high extent. In tumor-bearing mice, FTC-Suc-chi and
      FTC-Gly-chi were eliminated faster from the blood circulation than in normal
      mice, that is, with half-lives of 11 and 7 h, respectively. FTC-Suc-chi was less
      partitioned to the tumor tissue but accumulated more easily into it compared with
      FTC-Gly-chi. This suggested the enhanced permeability and retention (EPR) effect
      of Suc-chi and explained the previous result that a water-soluble Suc-chi
      mitomycin C conjugate injected intravenously exhibited a good effect against
      Sarcoma 180 solid tumor. FTC-Gly-chi showed greater distribution to the kidney
      than in normal mice. Urinary excretion studies indicated the faster excretion of
      both polymers in tumor-bearing mice. The molecular weight of the products
      excreted into urine indicated that both polymers should be pretty resistant to
      the hydrolytic enzyme, lysozyme. Taking toxicities into account, Suc-chi is
      considered to be available as a drug carrier showing long systemic retention and
      tumor accumulation.

PMID- 10077439
TI  - Properties of cationic liposomes composed of cationic lipid YKS-220 having an
      ester linkage: adequate stability, high transfection efficiency, and low
      cytotoxicity.
AB  - Cationic lipid N-[3-[2-(1,3-dioleoyloxy)propoxy-carbonyl]propyl]-N,N,N-trimethyla
      mmonium iodide (YKS-220) having a symmetrical and biodegradable structure was
      employed for the preparation of cationic liposomes with
      dioleoylphosphatidylethanolamine (DOPE). The stability, transfection activity in
      several cell lines and cytotoxicity of YKS-220 cationic liposomes were studied.
      It was found the YKS-220 cationic liposomes were very stable and their
      transfection activity remained even after storage at 4 degrees C for 12 months.
      The transfection activity of these liposomes was assayed using CHO, COS, and
      HepG2 cells and found to be comparable with, or better than, that of other
      cationic liposomes, such as N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium
      methylsulfate (DOTAP) liposome, N-[1-(2,3-dioleyloxy)propyl]-N,N,N
      trimethylammonium chloride (DOTMA) liposome (Lipofectin), and 2,3-dioleyloxy-N-[2
      (sperminecarboxamido)ethyl]-N,N-dimethyl -1-propanaminium trifluoroacetate
      (DOSPA) liposome (LipofectAMINE). In addition, the cytotoxicity of YKS-220
      cationic liposomes was far lower than that of other cationic liposomes.

PMID- 10077440
TI  - Pharmacokinetic drug interactions between ampiroxicam and sulfaphenazole in rats.
AB  - The aim of the present study was to determine the effect of sulfaphenazole (SP)
      on the pharmacokinetics of ampiroxicam (AM) which is metabolized by cytochrome P
      450 (CYP) 2C9, since SP is a potent inhibitor of CYP 2C9, and so a dramatic
      pharmacokinetic drug interaction between both drugs is assumed after dosing.
      Single intravenous and oral administrations of AM (5 and 7.5 mg/kg piroxicam
      equivalent, respectively) and SP (80 and 120 mg/kg, respectively) to rats did not
      significantly alter the elimination kinetics of AM and piroxicam (PX) converted
      from AM. When SP was preloaded orally at 2 h before the dosing of AM, and when AM
      and SP were orally coadministered for 7 d, the elimination of PX from plasma was
      slightly retarded and the area under the plasma concentration-time curve (AUC)
      was increased 77 and 53%, respectively, but not significantly, compared with
      those after AM alone. On the other hand, a significantly decreased metabolic
      conversion of PX to 5'-hydroxyPX in plasma was observed by these treatments
      (p<0.05). In order to clarify the mechanism for the interaction, hepatic and
      intestinal metabolizing enzyme activities, CYP, uridine 5'
      diphosphoglucuronyltransferase (UDPGT) and aryl esterase, were assayed after
      single and multiple oral administrations of AM or AM and SP. The enzyme
      activities were hardly inhibited by the treatment, indicating that the inhibition
      of CYP and hydrolytic enzymes by SP was approximately denied. These results
      suggest that SP does not significantly affect the pharmacokinetics of AM and PX
      in rats. However, the pharmacokinetic drug interaction between both drugs in man
      may not always be ignored.

PMID- 10077441
TI  - Lactoferrin inhibits Bacillus cereus growth and heme analogs recover its growth.
AB  - The growth of Bacillus cereus was markedly inhibited by the addition of
      lactoferrin and was recovered by the addition of FeCl3. The growth inhibition was
      also reversed by the addition of erythrocytes and hemoglobin. B. cereus can use
      heme or heme-protein complex (hemoglobin-haptoglobin and hematin-albumin
      complexes) as iron sources in iron deficient conditions. Therefore, B. cereus
      uses these heme or heme-protein complexes to prevent the growth inhibition of
      lactoferrin in vivo.

PMID- 10077442
TI  - Variation in glycosidase activity in soluble fractions in ICR/f rat lenses with
      the progression of cataract formation.
AB  - The current study reports active glycosidases in the lens of ICR/f rats, which
      generate a hereditary cataract approximately 90 d after birth, and the variation
      in enzyme activity with cataract progression. Seven active glycosidases, beta-D
      galactosidase, alpha-D-glucosidase, beta-D-glucosidase, beta-D-glucuronidase,
      beta-D-galactosaminidase, beta-D-glucosaminidase and alpha-D-mannosidase, were
      detected in ICR/f rat lenses. Of these, beta-D-glucuronidase and beta-D
      galactosidase showed a tendency to increase in activity with the cataract
      progression. Furthermore, beta-D-glucosidase and alpha-D-mannosidase showed a
      transitory increase in activity at the time of cataract formation. This result
      suggests that several glycosidases in the lens may be involved in the hereditary
      cataract formation. The optimal pH and temperature of the seven active
      glycosidases in rat lenses were also measured in this study.

PMID- 10077443
TI  - Study of structure--hepatoprotective relationships of oleanene-type
      triterpenoidal glucuronides obtained from several fabaceous plants on rat primary
      hepatocyte cultures.
AB  - The protective effects of nine oleanene-type triterpenoidal glucuronides obtained
      from several fabaceous plants (Lupinus polyphyllus x arboreus Hybrid, Astragalus
      complanatus, Wistaria brachybotrys) on in vitro immunological liver injury in
      primary cultured rat hepatocytes were studied. Although all tested saponins
      showed hepatoprotective action, the levels of activity of the individual saponins
      differed. Structure-activity relationships for the sapogenol moiety suggested
      that the presence of the carbonyl group at C-22 would show a similar
      hepatoprotective effect to that of the hydroxyl group at C-22 while the presence
      of the hydroxyl group at C-30 would reduce the hepatoprotective action. This
      structure-activity relationship substantiated other recently obtained data.
      Furthermore, the beta-orientation of the hydroxyl group at C-21 is more effective
      than the alpha-configuration in regard to the hepatoprotection. Furthermore,
      structure-activity relationships for the sugar moiety substantiated previously
      obtained data that the hydroxyl group at C-5" enhances the hepatoprotective
      action.

PMID- 10077444
TI  - Extended quasi-likelihood is useful for analyzing intra-individual variability in
      pharmacokinetic regression models.
AB  - The method of maximum extended quasi-likelihood (MEQL) can be viewed as an
      estimation method in the framework of generalized linear models. The method was
      applied to a pharmacokinetic problem in which the pharmacokinetic model was a
      nonlinear function of its parameters. The behavior of the method toward the
      estimation of a variance function was numerically compared with those of the
      generalized least squares (GLS) and extended least squares methods. In general,
      the MEQL and GLS methods were equally better. However, the MEQL estimator often
      showed smaller mean squared errors for the scaling parameter than the other two
      estimators. Such a generally comparable but partially distinct property of the
      MEQL method, as compared with the GLS method, is useful to pharmacokinetic
      analysis.

PMID- 10077445
TI  - Sensitivity of real time viral detection by an optical biosensor system using a
      crude home-made antiserum against measles virus as a ligand.
AB  - Virus identification in clinical materials during acute phase infections could
      give necessary information for the treatment of infections by human
      immunoglobulin (hIg) or interferon (IF). But because of a lack of information,
      most virus infections have not been treated. We have tried to develop a real time
      detection system for viruses in general using an optical biosensor and a model
      virus, Herpes simplex virus Type 1 (HSV-1), and have proved that the HSV-1 virus
      propagated in Vero cells and diluted in minimum essential medium (MEM) with 10%
      fetal bovine serum (FBS) could be detected in high sensitivity close to 10
      infectious units (50% tissue culture infective dose [TCID50] units) using
      purified cellular receptor molecules as the ligand because the receptor could be
      the most specific ligand. However, because ligands available for this system to
      identify various viral infections in general are limited, we also tested this
      system using a purified polyclonal antibody which contained many other antigens
      as the ligand, and produced sensitivity comparable to that using the receptor as
      a ligand. In this paper, we tested the sensitivity by this system under the worst
      condition. That is, we used a crude home-made rabbit antiserum against measles
      virus with host cell debris as a ligand. It was found that less than 500
      infectious (TCID50) units of virus were required for detection in a 100 microl
      solution, and that the efficacy of the commercially available hIg was also
      estimated by this system. This result suggested that this real time viral
      detection and titration system was applicable for the diagnosis of all viral
      infections even under difficult conditions without requiring any complex skills,
      with high enough sensitivity for clinical purposes. The efficacy of hIg
      preparations could also be evaluated by this system at the same time of the
      clinical material sampling.

PMID- 10077446
TI  - Pharmacokinetic evaluation of biodistribution data obtained with radiolabeled
      proteins in mice.
AB  - Radiolabeling of proteins is a widely used approach to study their in vivo
      disposition patterns. However, the obtained results may largely depend on the
      radiolabeling method used. The purpose of the present study was to investigate
      the effect of the radiolabeling method on the pharmacokinetic analysis of liver
      targeted protein in mice. Galactosylated bovine serum albumin (Gal-BSA) was
      labeled with 125I or 111In, using diethylenetriamine-pentaacetic dianhydride
      (cDTPA) or 1-(4-isothiocyanobenzyl)ethylenediaminetetraacetic acid (SCN-Bz-EDTA)
      as bifunctional chelating agents. The Gal-BSA was then injected in mice by a
      bolus intravenous injection. Samples of plasma, urine, liver, kidney, intestine
      and feces were collected at various time intervals and their radioactivity was
      measured. In none of the samples examined was there any significant difference in
      radioactivity distribution originating from the radiolabeling methods within 5
      min after administration. After this period, 125I radioactivity in the liver
      started to decrease significantly faster than that of 111In, which would indicate
      the intracellular degradation of the protein. Consequently, the reappearance of
      trichloracetic acid (TCA) soluble 125I radioactivity in the plasma occurred. But
      whereas the hepatic uptake clearance (CLliver) of [111In]DTPA-Gal-BSA remained
      constant during 8 h postinjection, the CLliver of [125I]Gal-BSA at 30 min
      represented only one eighth of its initial values. The CLliver of [111In]SCN-Bz
      EDTA-Gal-BSA resembled that of [111In]DTPA-Gal-BSA within 1 h of the experiment
      but it started to decline after this interval. The observed discrepancies most
      probably resulted from the formation of different radiolabeled metabolites in the
      hepatocytes and their different capability of crossing biological membranes. Our
      findings indicate that among the three methods employed, [111In]DTPA
      radiolabeling of Gal-BSA is the most appropriate method to study its tissue
      disposition.

PMID- 10077447
TI  - Western blotting for ginseng saponins, ginsenosides using anti-ginsenoside Rb1
      monoclonal antibody.
AB  - Ginsenosides separated by silica gel TLC were blotted to a polyvinylidene
      difluoride (PVDF) membrane which was treated with a NaIO4 solution followed by
      bovine serum albumine (BSA), resulting in a ginsenoside-BSA conjugate on a PVDF
      membrane. The blotted bands were stained with monoclonal antibody (MAb). The
      newly established Western blotting method was used for the determination of
      ginsenosides and their distribution in various Panax species.

PMID- 10077448
TI  - Western blotting method for the immunostaining detection of glucuronides of
      glycyrrhetic acid using anti-glycyrrhizin monoclonal antibody.
AB  - A method for detecting glucuronides of glycyrrhetic acid using Western blotting
      was investigated. Glucuronides of glycyrrhetic acid separated by silica gel TLC
      were transferred to a polyvinylidene difluoride membrane. The membrane was
      treated with sodium periodate solution followed by bovine serum albumin,
      resulting in a glucuronides of glycyrrhetic acid-BSA conjugate. Individual spots
      were stained by monoclonal antibody against glycyrrhizin. Immunostaining of
      glucuronides of glycyrrhetic acid was more sensitive compared to other staining
      methods. The newly established immunostaining method can be expanded to the
      distribution of glucuronides of glycyrrhetic acid in the plant body.

PMID- 10077449
TI  - Antiangiogenic activity of tumor necrosis factor-alpha production regulators
      derived from thalidomide.
AB  - Recently, we developed novel tumor necrosis factor (TNF)-alpha production
      regulators with a phthalimide skeleton derived from thalidomide. We show here
      that some of these compounds are more potent inhibitors than thalidomide of
      angiogenesis induced by basic fibroblast growth factor in a murine angiogenesis
      assay.

PMID- 10077450
TI  - Nucleotide sequence of the gene cluster containing the mphB gene for macrolide 2'
      phosphotransferase II.
AB  - Escherichia coli BM2506 produced macrolide 2'-phosphotransferase II [MPH (2')
      II]. A gene for MPH (2') II, designated mphB, is located on plasmids pTZ3721 and
      pTZ3723 in E. coli BM2506. In the present study, we determined the nucleotide
      sequence of the 6.5-kb EcoRI-PstI fragment containing mphB on pTZ3721. The DNA
      region of 6.5-kb EcoRI-PstI fragment contained five open reading frames (ORFs).
      ORF4 corresponded to mphB. Respective products deduced from ORF1, ORF2, ORF3, and
      ORF5 were similar to the penicillin-binding protein 4 of Streptomyces
      lactamduras, the repressor protein AcrR of the acrAB operon, the enzyme RdmC
      involved in the biosynthesis of the antibiotic aklavinone, and IS801 transposase
      like protein from Pseudomonas pseudoalcakigenes, respectively. Among these genes,
      ORF2, ORF3, and mphB formed a gene cluster with ORF2 in the lead sequence. Our
      results suggest that mphB may originate from an operon related to antibiotic
      biosynthesis.

PMID- 10077451
TI  - Geranylgeranylpyrophosphate plays a key role for the G1 to S transition in
      vascular smooth muscle cells.
AB  - Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of
      vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric
      analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the
      inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression,
      suggesting the importance of mevalonate itself and/or its metabolites in VSMC
      proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl
      pyrophosphate (GGPP), farnesyl pyrophosphate (FPP) and IPP (isopentenyl
      pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP,
      FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest
      were examined. Only GGPP restored the pravastatin-induced inhibition of DNA
      synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase
      from cytosol to membrane. By the addition of GGPP, Rho small GTPase are
      geranylgeranylated and translocated to membranes during G1/S transition. These
      data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among
      mevalonic acid metabolites for VSMC proliferation and the G1/S transition.

PMID- 10077452
TI  - Changes in the proliferative activities of cells in experimental atherosclerotic
      plaques during remodeling.
AB  - To investigate the relationship between cytologic alterations and cellular
      proliferation during atherosclerotic remodeling, we examined experimental
      atheromatous plaques by immunohistochemistry. Plaques were formed on rabbit
      aortas by cholesterol-enriched diets and mechanical stimulation over a period of
      2 months. Plaques were examined 1 month and 6 months after induction. We used
      antibodies RAM-11, HHF-35, and monoclonal anti-proliferating cell nuclear antigen
      (PCNA) antibody for detection of macrophages (Mphi), smooth muscle cells (SMC),
      and PCNA, respectively. One month after induction, the plaques revealed a
      thickened intima with a fibrofatty histologic pattern or accumulation of foam
      cells. With either histologic pattern, foam cells were found to be Mphi and
      proliferative activity was mainly observed in Mphi. Six months after induction,
      calcification and organization were seen on the induced plaques, suggesting
      progression of remodeling. There were fewer Mphi and more SMC compared with
      plaques examined 1 month after induction. Proliferative activity was observed
      mainly in SMC. We have demonstrated that the proliferative activity of cell types
      changes during remodeling of atheromatous plaques. Our results suggest an
      important relationship between the proliferative activity of SMC and remodeling.

PMID- 10077453
TI  - Influences of supplementary dietary tungsten on methionine metabolism in rabbits
      fed a low-cholesterol plus methionine diet.
AB  - Hyperhomocysteinemia results from an impaired methionine metabolism. Sulfite
      oxidase, which is an important enzyme in methionine metabolism, contains
      molybdenum. In contrast, tungsten has a molybdenum-antagonistic effect. Thus, we
      hypothesized that dietary tungsten may decrease plasma homocysteine levels and
      influence methionine metabolism. Male New Zealand White rabbits (n=15) were fed a
      low-cholesterol basal diet and then placed on three different diets: 0.1%
      cholesterol (Chol), Chol plus 1% methionine (Met), and Chol plus Met plus 0.1%
      tungsten (W). The animals received these diets for 20 weeks. Biochemical tests of
      blood and urine were performed. Plasma homocysteine levels were significantly
      lower in the Chol+Met+W group than in the Chol+Met group. Plasma levels of total
      cholesterol, triglyceride, lipid peroxide, and urinary 24-h taurine
      concentrations were higher in the Chol + Met + W group than in the Chol + Met
      group. In comparison, concentrations of 2, 3-diphosphoglycerate (2, 3-DPG),
      reduced glutathione (GSH) in erythrocytes, and urinary 24-h SO4(2) were lower in
      the Chol+Met+W group than in the Chol+Met group. From these results, tungsten
      could be expected to exhibit an antiatherogenic effect. Conversely, it may have
      effects on atherogenic factors. Thus, tungsten may play a number of roles in the
      methionine metabolism.

PMID- 10077454
TI  - Circulating thrombomodulin and hematological alterations in type 2 diabetic
      patients with retinopathy.
AB  - To clarify the relationship between circulating thrombomodulin (TM) and
      endothelial cell damage in diabetes mellitus, plasma levels of TM were
      quantitated by an enzyme linked immunoabsorbant assay (ELISA) in 164 type 2
      diabetes mellitus and 72 normal control subjects, and these levels were compared
      with those of von Willebrand factor antigen (vWf: Ag), thrombin antithrombin III
      complexes (TAT), plasmin-alpha2-plasmin inhibitor complexes (PIC), fibrinogen, D
      dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and
      plaque score of the common carotid artery assessed with high resolution B-mode
      ultrasonography. Plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and plaque
      score were significantly increased in the diabetic patients compared to the
      normal control subjects. Plasma TM levels showed significant correlation with
      vWf: Ag (r=0.350, p<0.0001), TAT (r = 0.334, p < 0.0001), PIC (r = 0.450, p <
      0.0001), AER (r = 0.334, p < 0.0001), IMT (r = 0.181, P<0.01), plaque score
      (r=0.385, p<0.0001). Among four groups of diabetic patients, divided based on
      their severity of diabetic retinopathy, there were no significant differences in
      age, sex, systolic and diastolic blood pressure levels, HbA,1c, or plasma lipid
      levels, although the plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and the
      plaque score in the patients with proliferative retinopathy were significantly
      higher than those of the healthy controls and patients with simple retinopathy.
      Among the 43 normoalbuminuric patients without intima-media thickness or
      thickened plaque (AER<30 mg/g Creatinine, IMT<1.0 mm, plaque score = 0), plasma
      levels of TM, vWf: Ag, TAT, PIC were significantly higher in those patients with
      retinopathy than in those without retinopathy. Multivariate analysis showed TM,
      TAT and PIC levels to be independent predictors of diabetic retinopathy. In
      conclusion, circulating TM reflects endothelial cell damage in patients with
      diabetic retinopathy, and hypercoagulability might play an important role in
      endothelial cell damage.

PMID- 10077455
TI  - Immunohistochemical and morphometric evaluations of coronary atherosclerotic
      plaques associated with myocardial infarction and diabetes mellitus.
AB  - Immunohistochemical and morphometrical studies were performed to elucidate the
      specificity of atherosclerosis in the descending branch (the segments 5 and 6) of
      the left coronary artery associated with acute myocardial infarction (AMI) in the
      anterior wall of the heart and non-insulin-dependent diabetes mellitus (NIDDM).
      The NIDDM without AMI group showed diffuse intimal thickening with smooth muscle
      cells, combined with much more intense immunostaining of tenascin than the non
      diabetic groups. The AMI without NIDDM group showed atheromatous thickening with
      decreased smooth muscle cells, a large number of macrophage and TUNEL-positive
      cells compared with the groups without AMI. However, the AMI with NIDDM group
      revealed atherosclerotic lesion with decreased smooth muscle cells, increased
      macrophages and TUNEL positive cells associated with the increased localization
      of tenascin and TGF-beta1 compared with the control. These findings suggest that
      the specificity of coronary atherosclerosis in diabetic patients may be the
      extensive atherosclerotic changes associated with increased tenascin. In AMI with
      NIDDM, increased TGF beta1 may induce apoptosis in the atheroma and coronary
      dysfunction, contributing to the development of acute myocardial infarction.

PMID- 10077456
TI  - Activin/follistatin and atherosclerosis--a review.
AB  - Activin-A, a member of the TGF-beta superfamily, has a variety of important
      biological functions. Concerning Mos, we demonstrated that MSR which has a key
      role in disposing of modified LDL is downregulated by activin-A. This leads to a
      decrease in binding, cell association, and degradation of Ac-LDL, resulting in
      the inhibition of foam cell formation. Follistatin, presumably by blocking the
      effect of intrinsic activin-A, upregulates MSR expression, thereby promoting Ac
      LDL disposal and foam cell formation. Because both activin-A and MSR are induced
      during Mo differentiation, these results suggest that MSR expression is
      suppressed by simultaneous production of activin-A in an autocrine manner. In
      addition to Mos, activin-A and follistatin exert influences on SMCs and ECs.
      Examination of in vivo expression of activin-A and follistatin revealed that they
      are present in various atherosclerotic lesions, including human coronary
      arteries, suggesting that they are locally produced. Activin-A and follistatin
      are produced by Mos, SMCs, and ECs in vitro. Thus, the activin-A/follistatin
      system plays an important role in the development of atherosclerosis.

PMID- 10077457
TI  - Hepatic lipase.
AB  - Hepatic lipase (HL) is an important enzyme that is involved in the metabolism of
      chylomicrons, intermediate density lipoproteins, and high density lipoproteins.
      HL may affect the liver uptake of remnant lipoproteins by modifying their
      compositions. HL also participates in the reverse cholesterol transport, thereby
      influencing the process of atherosclerosis. Several new functions of HL have
      recently been revealed. In this article, we review some of the recent progress
      based on studies using transgenic animals, with an emphasis on HL functions in
      remnant metabolism and atherosclerosis.

PMID- 10077458
TI  - Adverse events associated with ingestion of gamma-butyrolactone--Minnesota, New
      Mexico, and Texas, 1998-1999.
AB  - Products containing gamma-butyrolactone (GBL) are marketed for many claimed
      purposes, including to induce sleep, release growth hormone, enhance sexual
      activity and athletic performance, relieve depression, and prolong life. GBL is
      converted by the body into gamma-hydroxybutyrate (GHB), a drug banned outside of
      clinical trials approved by the Food and Drug Administration (FDA). Recognized
      manifestations of GHB toxicity include bradycardia, hypothermia, central nervous
      system depression, and uncontrolled movements. This report describes seven cases
      of GBL toxicity involving the product "Revivarant," which is labeled as
      containing 1.82 g of GBL per fluid ounce, reported from two hospital emergency
      departments (EDs) in Minnesota during October-December 1998 and summarizes an
      additional 34 cases of GBL toxicity reported to poison centers in New Mexico and
      Texas during October 1998-January 1999.

PMID- 10077459
TI  - Decline in cigarette consumption following implementation of a comprehensive
      tobacco prevention and education program--Oregon, 1996-1998.
AB  - In November 1996, residents of Oregon approved a ballot measure increasing the
      cigarette tax by 30 cents (to 68 cents per pack). The measure stipulated that 10%
      of the additional tax revenue be allocated to the Oregon Health Division (OHD) to
      develop and implement a tobacco-use prevention program. In 1997, OHD created
      Oregon's Tobacco Prevention and Education Program (TPEP), a comprehensive,
      community-based program modeled on the successful tobacco-use prevention programs
      in California and Massachusetts. To assess the effects of the tax increase and
      TPEP in Oregon, OHD evaluated data on the number of packs of cigarettes taxed
      before (1993-1996) and after (1997-1998) the ballot initiative and implementation
      of the program. Oregon's results also were compared with national data. This
      report summarizes the results of the analysis, which indicate that consumption of
      cigarettes in Oregon declined substantially after implementation of the excise
      tax and TPEP and exceeded the national rate of decline.

PMID- 10077460
TI  - Neighborhood safety and the prevalence of physical inactivity--selected states,
      1996.
AB  - Physical inactivity is an important risk factor for premature morbidity and
      mortality, especially among high-risk populations. Although health-promotion
      programs have targeted high-risk groups (i.e., older adults, women, and
      racial/ethnic minorities), barriers exist that may affect their physical activity
      level. Identifying and reducing specific barriers (e.g., lack of knowledge of the
      health benefits of physical activity, limited access to facilities, low self
      efficacy, and environmental issues [2-6]) are important for efforts designed to
      increase physical activity. Concerns about neighborhood safety may be a barrier
      to physical activity. To characterize the association between neighborhood safety
      and physical inactivity, CDC analyzed data from the 1996 Behavioral Risk Factor
      Surveillance System (BRFSS) in Maryland, Montana, Ohio, Pennsylvania, and
      Virginia. This report summarizes the results of this analysis, which indicate
      that persons who perceived their neighborhood to be unsafe were more likely to be
      physically inactive.

PMID- 10077461
TI  - Recall of Tripedia vaccine.
AB  - On January 27, 1999, the Food and Drug Administration initiated a voluntary
      recall of Tripedia diphtheria and tetanus toxoids and acellular pertussis vaccine
      (DTaP), lot number 0916490, manufactured by Pasteur Merieux Connaught USA.
      Routine post-release stability testing completed in January 1999 indicated that
      the potency of the diphtheria toxoid component of this lot was below
      specification. The potency of the tetanus and pertussis components of this lot
      was acceptable.

PMID- 10077462
TI  - Paramagnetic oligonucleotides: contrast agents for magnetic resonance imaging
      with proton relaxation enhancement effects.
AB  - An antisense paramagnetic oligonucleotide analogue targeted to a model
      macromolecular receptor (5S rRNA) was prepared. The paramagnetic agent's
      relaxivity (dependence of the relaxation rate on paramagnetic agent
      concentration) in the presence and absence of the macromolecular receptor was
      measured at 1.5 and 6.3 T. The relaxivity of the targeted agent increased
      specifically in the presence of the macromolecular receptor (16% at 6.3 T and 15%
      at 1.5 T). This effect was specific for a paramagnetic oligonucleotide targeted
      to the receptor and was larger than the relaxivity enhancement due simply to
      receptor-induced viscosity differences. Maximizing this relaxivity enhancement of
      tumor targeted paramagnetic oligonucleotides will aid in contrast agent
      development for magnetic resonance imaging.

PMID- 10077463
TI  - 99mTc-labeled MIBG derivatives: novel 99mTc complexes as myocardial imaging
      agents for sympathetic neurons.
AB  - Radioactive-iodine-labeled meta-iodobenzylguanidine (MIBG) is currently being
      used as an in vivo imaging agent to evaluate neuroendocrine tumors as well as the
      myocardial sympathetic nervous system in patients with myocardial infarct and
      cardiomyopathy. It is generally accepted that MIBG is an analogue of
      norepinephrine and its uptake in the heart corresponds to the distribution of
      norepinephrine and the density of sympathetic neurons. A series of MIBG
      derivatives containing suitable chelating functional groups N2S2 for the
      formation of [TcvO]3+N2S2 complex was successfully synthesized, and the 99mTc
      labeled complexes were prepared and tested in rats. One of the compounds,
      [99mTc]2, tested showed significant, albeit lower, heart uptakes post iv
      injection in rats (0.21% dose/g at 4 h) as compared to [125I]MIBG (1.7% dose/g at
      4 h). The heart uptake of the 99mTc-labeled complex appears to be specific and
      can be reduced by co-injection with nonradioactive MIBG or by pretreatment with
      desipramine, a selective norepinephrine transporter inhibitor. Further evaluation
      of the in vitro uptake of [99mTc]2 in cultured neuroblastoma cells displayed
      consistently lower, but measurable uptake (approximately 10% of that for
      [125I]MIBG). These preliminary results suggested that the mechanisms of heart
      uptake of [99mTc]2 may be related to those for [125I]MIBG uptake. If suitable
      99mTc-labeled MIBG derivatives can be further developed, the prevalent
      availability of 99mTc in nuclear medicine clinics will allow them to be readily
      available for widespread application.

PMID- 10077464
TI  - Synthesis and characterization of a photoactivatable glycoaryldiazirine for
      surface glycoengineering.
AB  - Biological systems make considerable use of specific molecular interactions. Many
      biomolecules involved in biorecognition are glycosylated, the carbohydrate moiety
      playing an essential role. Controlled surface glycoengineering is thus of crucial
      importance in biosensing, cell guidance, and biomedical applications. This study
      describes the synthesis of an aryldiazirine-derivatized galactose and the
      functionalization of surfaces by carbohydrates using photochemical immobilization
      techniques. A photoactivatable glycosylated reagent was synthesized by addition
      of thiogalactopyranose to the maleimide group of N-[m-[3
      (trifluoromethyl)diazirin-3-yl]phenyl]-4-maleimidobutyr amide (MAD) to give N-[m
      [3-(trifluoromethyl)diazirin-3-yl]phenyl]-4-[3-thio (1-D
      galactopyranosyl)succinimidyl]butyramide (MAD-Gal). The structure of the newly
      synthesized molecule was confirmed by UV spectroscopy, photoactivation, 1H NMR,
      and 13C NMR. MAD-Gal was immobilized on thin diamond films by photoactivation of
      the diazirine function (350 nm). Surface modification was investigated by XPS (X
      ray photoelectron spectroscopy) and ToF-SIMS (time-of-flight secondary ion mass
      spectrometry). Imaging ToF-SIMS was applied to detect glycopatterns generated by
      mask-assisted lithography.

PMID- 10077465
TI  - Structure-binding relationships for the interaction between a vancomycin
      monoclonal antibody Fab fragment and a library of vancomycin analogues and
      tracers.
AB  - A series of vancomycin analogues and tracers were synthesized, and their binding
      interactions with an anti-vancomycin Fab fragment were evaluated under mass
      transport limiting conditions using surface plasmon resonance detection.
      Differences observed in binding interactions were utilized to define the
      vancomycin structural elements critical for antibody recognition. Major
      structural regions of vancomycin shown to play an important role in anti
      vancomycin Fab fragment recognition include two sugar moieties and one
      chlorinated phenyl ring. The N-methylleucyl residue, the carboxy terminal
      residue, and residues in the peptide-binding region of vancomycin have minimal
      impact on the anti-vancomycin Fab fragment/vancomycin binding interaction. The
      selection of an antibody with such binding properties plays a critical role in
      the development of a vancomycin immunoassay that employs stable calibrators and
      controls.

PMID- 10077466
TI  - High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat
      peptide conjugates.
AB  - A biocompatible, dextran coated superparamagnetic iron oxide particle was
      derivatized with a peptide sequence from the HIV-tat protein to improve
      intracellular magnetic labeling of different target cells. The conjugate had a
      mean particle size of 41 nm and contained an average of 6.7 tat peptides.
      Derivatized particles were internalized into lymphocytes over 100-fold more
      efficiently than nonmodified particles, resulting in up to 12.7 x 10(6)
      particles/cell. Internalized particles localized in cytoplasm and nuclear
      compartments as demonstrated by fluorescence microscopy and immunohistochemistry.
      Labeled cells were highly magnetic, were detectable by NMR imaging, and could be
      retained on magnetic separation columns. The described method has potential
      applications for in vivo tracking of magnetically labeled cells by MR imaging and
      for recovering intracellularly labeled cells from organs.

PMID- 10077467
TI  - Novel paramagnetic macromolecular complexes derived from the linkage of a
      macrocyclic Gd(III) complex to polyamino acids through a squaric acid moiety.
AB  - Macromolecular Gd(III) complexes may find useful application as contrast agents
      for magnetic resonance angiography (MRA). Herein two novel systems are reported,
      namely Gd(DO3ASQ)3-lys16 and Gd(DO3ASQ)30-orn114. Their syntheses are based on
      the ability of the squaric acid moiety to act as a linker between the DO3A
      (1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid) chelate moiety and the
      polyamino acidic chain. Moreover, the squaric acid participates in the
      coordination cage of the Gd(III) ion. The investigation of 1H and 17O NMR
      relaxation processes of solvent water nuclei allowed a detailed characterization
      of the systems under study. Gd(DO3ASQ)30-orn114 displays a remarkable ability to
      enhance the water proton relaxation rate of its solutions, and it may be
      considered as potential contrast agent for MRA applications.

PMID- 10077468
TI  - Synthesis and characterization of photoreactive insulin-like growth factor 1
      derivatives for receptor analysis.
AB  - Recombinant human insulin-like growth factor 1 (hIGF-1) was reacted with 4
      azidosalicylic acid (Asa) to synthesize photoreactive IGF-1 derivatives.
      Depending on the time of reaction and the Asa/IGF-1 ratio, a mixture of mono-,
      bis-, and trisacylated derivatives and one tetraacylated derivative was produced,
      which was separated by reversed-phase HPLC. HPLC, PAGE, and MALDI mass
      spectrometry were used to determine the degree of the acylation and location of
      the photolabel insertion. After iodination of the three monoacylated
      photoreactive IGF-1 derivatives, the specific labeling of the receptor could be
      proved. Together with a comparative investigation in which B29-Asa-insulin was
      used, the results suggest corresponding contact areas for IGF-1 and insulin with
      the insulin receptor ectodomain.

PMID- 10077469
TI  - Optimized conditions to couple two water-soluble biomolecules through alkylamine
      thiolation and thioetherification.
AB  - A simple method for introducing, in buffered saline, a reactive sulfhydryl group
      on water-soluble molecules bearing an alkyl-amino group is described. This method
      is based on the use of two water-soluble reagents: 2-iminothiolane and 6,6'
      dithiodinicotinic acid. The first one is open upon reaction with an amino group,
      and the generated thiol group is immediately protected by action of the second
      reagent. The optimal conditions were determined by taking into account the
      stability and the reactivity of both reagents with regards to pH and temperature.
      This method was validated through two applications, the substitution of bovine
      serum albumin with a bromoacetyl peptide and the substitution of an amino link at
      the 5' end of an oligonucleotide by reaction with either a fluorescent tag,
      iodoacetamidofluorescein, or a bromoacetyl peptide, upon reduction of the
      protected disulfide bridge with a third water-soluble reagent, namely tris(2
      carboxyethyl)phosphine.

PMID- 10077470
TI  - Tresyl-mediated synthesis: kinetics of competing coupling and hydrolysis
      reactions as a function of pH, temperature, and steric factors.
AB  - Kinetic parameters have been measured for coupled nucleophilic and solvolytic
      reactions of 2,2,2-trifluoroethanesulfonyl (tresyl)-modified poly(ethylene
      glycol) based on a system of coupled differential equations implied by recently
      proposed elementary reaction mechanisms. Fitted kinetic parameters were found to
      be strong functions of pH, temperature, and steric factors. To maximize the total
      yield of coupled amine as well as the fraction of secondary amine linkages, our
      model predicts that it is desirable to run tresyl coupling reactions at low
      temperatures at pH approximately 8.0, depending on the amine pKa for primary,
      unhindered amines. For branched primary amines, our data favor room temperature
      at a slightly higher pH.

PMID- 10077471
TI  - Methods for dual, site-specific derivatization of bovine pancreatic trypsin
      inhibitor: trypsin protection of lysine-15 and attachment of fatty acids or
      hydrophobic peptides at the N-terminus.
AB  - To produce a series of model membrane proteins, bovine pancreatic trypsin
      inhibitor (BPTI) has been modified by specifically attaching reporter groups to
      Lys-15 and fatty acids or hydrophobic peptides at the N-terminus. Lys-15 of BPTI
      was protected by trypsin bound to BPTI, then O-methylisourea (OMIU) was used to
      guanidinate all unprotected lysines. The N-terminal amine was then reacted with
      several saturated fatty acid anhydrides from 8 to 18 carbons in length, or with
      an SMCC cross-linker. Cysteine-containing hydrophobic peptides, cleaved from
      resin in the presence of sodium dodecyl sulfate (SDS), were then attached to the
      protein via the N-terminal cross-linker. The methods described yield a unique,
      chemically modified protein which can carry site-specific modifications at two
      distinct residues. The resulting proteins are ideal for diffusional or
      partitioning studies on model and biological membranes.

PMID- 10077472
TI  - Labeling of monoclonal antibodies with diethylenetriaminepentaacetic acid
      appended radioiodinated peptides containing D-amino acids.
AB  - The optimal use of radioiodinated internalizing monoclonal antibodies (mAbs) for
      radioimmunotherapy necessitates the development of practical methods for
      increasing the level of retention of 131I in the tumor. Lysosomally trapped
      ("residualizing") iodine radiolabels that have been previously designed are based
      mostly on carbohydrate-tyramine adducts, but these methods have drawbacks of low
      overall yields and/or high levels of mAb aggregation. We have developed a method
      using thiol-reactive diethylenetriaminepentaacetic acid (DTPA)-peptide adducts
      wherein the peptides are assembled with one or more D-amino acids, including D
      tyrosine. Two such substrates, R-Gly-D-Tyr-D-Lys[1-(p
      thiocarbonylaminobenzyl)DTPA], referred to as IMP-R1, and [R-D-Ala-D-Tyr-D-Tyr-D
      Lys]2(CA-DTPA), referred to as IMP-R2, wherein R is 4-(N
      maleimidomethyl)cyclohexane-1-carbonyl, were synthesized by preparing functional
      group-protected peptides on a solid phase, selectively derivatizing the lysine
      side chain with 1-(p-isothiocyanatobenzyl)DTPA or DTPA dianhydride (CA-DTPA),
      deprotecting other functional groups, and finally derivatizing the peptide's N
      terminus so it contained a maleimide group. Radioiodinations of the peptides
      followed by conjugations to disulfide-reduced mAbs, carried out as a one-vial
      procedure, resulted in 32-89% overall yields, at specific activities of 1.8-11. 1
      mCi/mg, with less than 2% aggregation. Two internalizing mAbs, LL2 (anti-CD 22 B
      cell lymphoma mAb) and RS7 (an anti-adenocarcinoma mAb which targets EGP-1
      antigen), labeled with this procedure exhibited a 2-3-fold better cellular
      retention in Ramos and Calu-3 tumor cell lines, in vitro, respectively, compared
      to the same mAbs radioiodinated with the chloramine-T method. The rationale for
      the new approach, syntheses, radiochemistry and in vitro data are presented.

PMID- 10077473
TI  - Design, synthesis, and spectroscopic properties of peptide-bridged fluorescence
      energy-transfer cassettes.
AB  - A general partial solid-phase synthetic scheme was developed for the synthesis of
      energy-transfer cassettes with the donor and acceptor dyes bridged by a peptide.
      In these cassettes, 6-carboxyfluorescein (Fam) served as a donor. For the second
      dye, 6-carboxy-X-rhodamine (Rox) was used as a fluorescent acceptor or erythrosin
      B as a quencher. Different peptides bearing Rox at the amino terminus and Fam
      linked through different diamines to the carboxyl terminus were synthesized to
      examine the effects of the chain length and rigidity on energy-transfer
      efficiency. The ratio of emission intensities at 605 nm of the acceptor dye (ROX)
      in the cassette Rox-GPPPEPPP-p-xylylenediamine-Fam versus free ROX with 488 nm
      excitation was approximately 14 and is similar to that obtained for optimized
      oligonucleotide primers bearing the same dyes [Ju, J., Ruan, C., Fuller, C. W.,
      Glazer, A. N., and Mathies, R. A. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 4347
      4351].

PMID- 10077474
TI  - Comb-type prepolymers consisting of a polyacrylamide backbone and poly(L-lysine)
      graft chains for multivalent ligands.
AB  - The comb-type copolymers consisting of a polyacrylamide (PAAm) backbone and
      poly(L-lysine) (PLL) graft chains have been prepared as the "prepolymer" for
      designing multivalent ligands. To regulate the length and density of the clusters
      of primary amino groups, the Nalpha-carboxyanhydride of Nepsilon-carbobenzoxy
      (CBZ)-L-lysine was first polymerized using p-vinylbenzylamine as an initiator.
      The resulting poly(CBZ-L-lysine) macromonomer was then radically copolymerized
      with AAm, followed by the deprotection of amino groups. For the model study, the
      reactive clusters of primary amino groups were completely converted into anion
      clusters by the reaction with succinic anhydride. The model multivalent ligands
      having the biotin label on the PAAm backbone were prepared by the
      terpolymerization of the macromonomer, AAm, and the biotin derivative having a
      vinyl group. The enzyme-linked immunosorbent assay showed that the biotin with no
      spacer on the PAAm backbone was recognized by the avidin-peroxidase conjugate
      specifically. Therefore, the highly sensitive detection of the interaction
      between cells and various model multivalent ligands was possible. The selective
      labeling onto the PAAm backbone revealed that the converted anion clusters of
      graft chains interacted exclusively with the cell and that the backbone was inert
      to the interaction with the cell. These results indicate that the various PAAm
      graft-PLL comb-type copolymers with the defined length and density of the PLL
      grafts are the potential prepolymers to investigate and to optimize the affinity
      of the multivalent ligands for receptors.

PMID- 10077475
TI  - 99mTc-labeling and in vivo studies of a bombesin analogue with a novel water
      soluble dithiadiphosphine-based bifunctional chelating agent.
AB  - Recent progress in the synthesis of water-soluble phosphine ligand systems and
      their corresponding 99mTc complexes prompted the development of a new
      bifunctional chelating agent (BFCA) based on a tetradentate dithiadiphosphine
      framework (P2S2-COOH). The detailed synthesis of this new BFCA is described here.
      The corresponding 99mTc complex, 99mTc-P2S2-COOH, can be formed in >95% yield. To
      demonstrate the potential of this chelate to efficiently label peptides, 99mTc
      P2S2-COOH was coupled to the N-terminal region of the truncated nine-amino acid
      bombesin analogue, 5-Ava-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 [BBN(7-14)], to form
      99mTc-P2S2-BBN(7-14). Conjugation to the peptide was performed in borate buffer
      (pH 8.5) by applying the prelabeling approach in yields of >60%. In competitive
      binding assays, using Swiss 3T3 mouse fibroblast cells against [125I
      Tyr4]bombesin, Re-P2S2-BBN(7-14) exhibited an IC50 value of 0.8 +/- 0.4 nM. The
      pharmacokinetic studies of 99mTc-P2S2-BBN(7-14) and its ability to target tissue
      expressing gastrin-releasing peptide (GRP) receptors were performed in normal
      mice. The 99mTc-P2S2-BBN(7-14) exhibited fast and efficient clearance from the
      blood pool (0.6 +/- 0.1% ID, 4 h postinjection) and excretion through the renal
      and hepatobiliary pathways (56.4 +/- 8.2 and 28.1 +/- 7.9% ID, 4 h postinjection,
      respectively). Significant uptake in the pancreas was observed (pancreatic acini
      cells express bombesin/GRP receptors), producing pancreas:blood and
      pancreas:muscle ratios of ca. 22 and 80, respectively, at 4 h postinjection.

PMID- 10077476
TI  - Synthesis and electrochemistry of anthraquinone-oligodeoxynucleotide conjugates.
AB  - Electroactive oligodeoxynucleotides (ODNs) with specific base sequences have a
      potential application as electrical sensors for DNA molecules. To this end, a
      phosphoramidite that bears a 9, 10-anthraquinone (AQ) group tethered to the 2'-O
      of the uridine via a hexylamino linker, 2'-O-[6-[2-oxo(9, 10-anthraquinon-2
      yl)amino]hexyl]-5'-O-(4,4'-dimethoxytrityl)uridi ne 3'-[2-(cyanoethyl)bis(1
      methylethyl)phosphoramidite] (3), has been synthesized and used to prepare three
      ODNs with tethered AQs using standard phosphoramidite chemistry. The synthetic
      methodology thus allows the synthesis of ODNs with electroactive tags attached to
      given locations in the base sequence. Cyclic voltammetric behavior of these AQ
      ODN conjugates was examined in aqueous buffer solutions at a hanging mercury drop
      electrode. At slow sweep rates, nearly reversible two-electron waves
      characteristic of an adsorbed anthraquinone/hydroquinone redox couple was
      observed for all of the AQ-ODN conjugates. Approximate Langmuirian isotherms were
      found for the AQ-ODNs with molecular footprints, calculated from the saturation
      coverages, that scaled with molecular size. The cyclic voltammetric response of
      the duplexes formed from the AQ-ODNs and their complementary ODN was complicated
      by the competitive adsorption of the individual ODNs and possibly the duplex
      species as well.

PMID- 10077477
TI  - Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic
      polymers.
AB  - Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone
      are more effective than monomeric SA at inhibiting influenza-induced
      agglutination of red blood cells. However, "polymeric inhibitors" based on
      polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic
      alternative to polyacrylamide and may provide a variety of potential synthetic
      inhibitors of influenza virus adhesion due to the wide range of available polymer
      structures. We evaluated several dendritic polymeric inhibitors, including
      spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft
      polymers, for the ability to inhibit virus hemagglutination (HA) and to block
      infection of mammalian cells in vitro. Four viruses were tested: influenza A H2N2
      (selectively propagated two ways), X-31 influenza A H3N2, and sendai. The most
      potent of the linear and spheroidal inhibitors were 32-256-fold more effective
      than monomeric SA at inhibiting HA by the H2N2 influenza virus. Linear-dendron
      copolymers were 1025-8200-fold more effective against H2N2 influenza, X-31
      influenza, and sendai viruses. The most effective were the comb-branched and
      dendrigraft inhibitors, which showed up to 50000-fold increased activity against
      these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent
      reduction of influenza infection in mammalian cells by polymeric inhibitors, the
      first such demonstration for multivalent SA inhibitors. Effective dendrimer
      polymers were not cytotoxic to mammalian cells at therapeutic levels. Of
      additional interest, variation in the inhibitory effect was observed with
      different viruses, suggesting possible differences due to specific growth
      conditions of virus. SA-conjugated dendritic polymers may provide a new
      therapeutic modality for viruses that employ SA as their target receptor.

PMID- 10077478
TI  - Monoclonal antibody conjugates of doxorubicin prepared with branched linkers: A
      novel method for increasing the potency of doxorubicin immunoconjugates.
AB  - Immunoconjugates of monoclonal antibody BR96 and Doxorubicin have been prepared
      using a novel series of branched hydrazone linkers. Since each linker bound to
      the mAb carries two DOX molecules, the DOX/mAb molar ratios of these conjugates
      were approximately 16, twice that of those previously prepared with single-chain
      hydrazone linkers. The conjugates were stable at a physiological pH of 7, but
      released DOX rapidly at lysosomal pH 5. The branched series of BR96 conjugates
      demonstrated antigen-specific cytotoxicity, and were more potent in vitro than
      the single-chain conjugate on both a DOX (4-14-fold) and mAb (7-23-fold) basis.
      The results suggest that, by using the branched linker methodology, it is
      possible to significantly reduce the amount of mAb required to achieve antigen
      specific cytotoxic activity. In this paper, the synthesis and in vitro biology of
      branched chain immunoconjugates are described.

PMID- 10077479
TI  - Targeting folate receptor with folate linked to extremities of poly(ethylene
      glycol)-grafted liposomes: in vitro studies.
AB  - Conjugates of three components, folic acid-poly(ethylene glycol)
      distearoylphosphatidylethanolamine (FA-PEG-DSPE), derived from PEG with molecular
      masses of 2000 and 3350 Da were synthesized by a carbodiimide-mediated coupling
      of FA to H2N-PEG-DSPE. The conjugates were characterized by 1H NMR, MALDI-TOF,
      and HPLC analysis of enzymatic cleavage with carboxypeptidase G. As a prototype
      of a folate receptor (FR)-targeted system, the conjugates were formulated at 0.5
      mol % phospholipid in hydrogenated phosphatidylcholine/cholesterol liposomes with
      or without additional methoxyPEG2000-DSPE. In vitro binding studies were
      performed with sublines of M109 (murine lung carcinoma) and KB (human epidermal
      carcinoma) cells each containing high and low densities of FR. FA-PEG-DSPE
      significantly enhanced liposome binding to tumor cells. The best binding was
      observed when FA-PEG liposomes contained no additional mPEG-lipid. In fact, our
      experiments showed that the presence of mPEG on liposomal surfaces significantly
      inhibited FA-PEG-liposome binding to FR. Increasing the molecular mass of the PEG
      tether from 2000 to 3350 Da improved the FR binding, particularly in the case of
      mPEG-coated liposomes. The FA-PEG liposomes bound to M109-HiFR cells very avidly
      as demonstrated by the inability of free FA (used in a 700-fold excess either at
      the beginning or at the end of the incubation) to prevent the cell binding. This
      is in contrast to the 5-10-fold lower cell binding activity of mPEG-FA compared
      to that of free FA, and likely to be related to the multivalent nature of the
      liposome-bound FA. Only 22% of FA-PEG3350 and 32% of FA-PEG3350/mPEG cell
      associated liposomes could be removed by exposure to pH 3, conditions that
      dissociate FA-FR, suggesting that more than two-thirds of the bound liposomes
      were internalized during incubation for 24 h at 37 degrees C. FA-targeted
      liposomes also show enhanced nonspecific binding to extracellular tissue culture
      components, a phenomenon especially relevant in short incubation time
      experiments.

PMID- 10077480
TI  - Duplex recognition by oligonucleotides containing 2'-deoxy-2'-fluoro-D-arabinose
      and 2'-deoxy-2'-fluoro-D-ribose. Intermolecular 2'-OH-phosphate contacts versus
      sugar puckering in the stabilization of triple-helical complexes.
AB  - To gain insight into the origins of the large binding affinity of RNA toward
      target duplexes, 2'-deoxy-2'-fluororibonucleic acid (2'F-RNA) and 2'-deoxy-2'
      fluoroarabinonucleic acid (2'F-ANA) were tested for their ability to recognize
      duplex DNA, duplex RNA, and RNA-DNA hybrids. 2'F-RNA, 2'F-ANA, and the
      corresponding control single-stranded (ss) DNA strands were shown to form triple
      helical complexes only with duplex DNA and hybrid DNA (Pu)-RNA (Py), but not with
      duplex RNA and hybrid RNA (Pu)-DNA (Py). In contrast, an RNA third strand
      recognized all four possible duplexes (DD, DR, RD, and RR) as previously
      demonstrated by Roberts and Crothers [(1992) Science 258, 1463-1466]. The 2'F-RNA
      (C3'-endo) strand exhibited significantly reduced affinity for duplexes compared
      to an unmodified RNA (C3'-endo) strand. These findings are consistent with the
      intermolecular 2'-OH-phosphate contact mechanism proposed by Escude et al.
      [(1993) Nucleic Acids Res. 24, 5547-5553], as a ribo 2'-F atom should not
      interact with a negatively charged phosphate. In addition, they emphasize the
      role of the 2'-OH ribose as a general recognition and binding determinant of RNA.
      The 2'-F arabino modification (2'F-ANA, C2'-endo) led to a considerable increase
      in the binding affinity for duplex DNA, as compared to those of DNA and 2'F-RNA
      third strands. This is likely to be the result of a greater population of C2'
      endo pucker of the 2'F-ANA compared to DNA. The enhancement observed for 2'F-ANA
      strands toward duplex DNA is comparable to that observed with 2'-OMe RNA. Since
      2'F-ANA has been shown to be more resistant to nuclease degradation than DNA,
      these results are likely to stimulate experimental work on arabinose derivatives
      in laboratories concerned with targeting DNA sequences in vivo ("antigene"
      strategy).

PMID- 10077481
TI  - Quantitative analysis of derivatized proteins prepared with pyridyl disulfide
      containing cross-linkers by high-performance liquid chromatography.
AB  - Determination of the introduced moieties into derivatized proteins is an
      essential step in the preparation and quality control of chemically defined
      immunoconjugates. For the derivatized proteins using pyridyl disulfide-containing
      cross-linkers such as N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and 4
      succinimidyloxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)tolu ene (SMPT), the
      derivatization degree (ratio of pyridyl disulfide moieties to protein) has been
      traditionally determined by measuring the absorbance of both the derivatized
      protein and 2-thiopyridone (2-TP) released from the dithiothreitol (DTT)
      treatment (spectrophotometric method). This method, however, causes several
      problems including false high and low determinations of the protein and 2-TP,
      respectively, low selectivity, poor reproducibility, and relatively large amounts
      of sample consumption. A quantitative determination method of the derivatization
      ratios using bovine serum albumin derivatized with SPDP and SMPT as the model
      system has been developed. The concentration of protein and 2-TP released from
      the DTT treatment of derivatized proteins was determined directly without
      consideration of different reagents used and their concentrations. The present
      HPLC method was proved to be better in terms of accuracy, selectivity, and
      reproducibility with micro sample consumption. Moreover, this HPLC method can be
      directly applied to all derivatized proteins prepared with pyridyl disulfide
      containing cross-linkers.

PMID- 10077482
TI  - Thiol-reactive luminescent chelates of terbium and europium.
AB  - Thiol-reactive lanthanide complexes have been synthesized that are luminescent
      when bound to terbium and/or europium. The complexes consist of a
      diethylenetriaminepentaacetate (DTPA) chelate covalently joined through one amide
      bond to a chromophore, carbostyril 124, and via a second amide bond to a
      maleimide, bromoacetamide, or pyridyldithio moiety. Site-specific attachment and
      characterization of the complexes attached to DNA-activating protein NtrC, to
      various sites on myosin, or to DNA are presented. The compounds coordinate a
      surprisingly large number of ligation sites of terbium when a hydrazide spacer is
      used between the chelate and thiol-reactive moiety, although this extra ligation
      can cause quenching when europium is used. Synthesis is a simple two- or three
      step reaction, and purification is straightforward. The compounds should be
      useful as nonisotopic replacements, as long-lifetime probes in imaging, and as
      donors in luminescence resonance energy transfer. They are examples of a wide
      class of chelates that can be made conjugatable via readily available hetero- or
      homo-bifunctional linkers.

PMID- 10077483
TI  - Total solid-phase synthesis of 1,4,7,10-tetraazacyclododecane-N,N', N'',N'''
      tetraacetic acid-functionalized peptides for radioimmunotherapy.
AB  - A convenient approach to the functionalization of peptides with the macrocyclic
      1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) moiety has
      been developed. Protected components (using tert-butyl or tert-butyloxycarbonyl
      groups) of both the peptide and the chelate were assembled on the same solid
      resin support. Deprotection and cleavage of the resin-bound DOTA-peptides were
      performed in one step using a trifluoroacetic acid cleavage mixture to yield free
      DOTA-peptide amides.

PMID- 10077484
TI  - A novel superoxide dismutase-based trap for peroxynitrite used to detect entry of
      peroxynitrite into erythrocyte ghosts.
AB  - Peroxynitrite (ONOO-) is a relatively stable oxidant produced by activated
      macrophages and neutrophils. To detect peroxynitrite, a novel human superoxide
      dismutase (SOD) trap was developed by substituting a tyrosine near the copper in
      the active site. The copper can catalyze nitration of this tyrosine by
      peroxynitrite. The nitrated tyrosine can serve as a reporter for peroxynitrite by
      measuring the extent of nitration with Western blots developed with a
      nitrotyrosine antibody. The new SOD mutant differs from bovine SOD whose sole
      tyrosine is far removed from the active site. Nitration of bovine SOD was second
      order with respect to SOD concentration, whereas nitration of the new mutant SODs
      followed first-order kinetics with respect to peroxynitrite. The tyrosine SODs
      were used to assess whether peroxynitrite crosses erythrocyte membranes through
      the band 3 anion exchange protein. Tyrosine-containing SOD entrapped within
      normal human erythrocyte ghosts became nitrated in proportion to peroxynitrite
      concentration. The band 3 anion exchange protein inhibitors, phenyl
      isothiocyanate (PITC) and 4, 4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS),
      inhibited up to 90% of the nitration. The erythrocyte membrane proteins,
      spectrin, band 3 anion exchange protein, and proteins 4.1 and 4.2, were also
      nitrated. Nitration of erythrocyte membrane proteins was also inhibited by PITC
      and DIDS. These data suggest that the band 3 anion exchange protein is the major
      route for the entry of peroxynitrite into erythrocytes. The ability of
      peroxynitrite to cross cell membranes can contribute to its toxicity by allowing
      access to intracellular target molecules.

PMID- 10077485
TI  - Superoxide free radical generation by Amadori compounds: the role of acyclic
      forms and metal ions.
AB  - Generation of oxygen free radicals by glycated proteins is widely believed to be
      one of the causes of oxidative stress in diabetes and aging. Metal ion catalysis
      is regarded as an essential part of the oxidative mechanism. In this work, we
      also considered an alternative "metal-free" superoxide radical formation by a
      number of fructose-amino acids (Amadori compounds) derived from glycine and
      lysine, which represent the simplest models for early glycated proteins. In the
      superoxide dismutase-dependent cytochrome c assay, 1 mM Chelex-treated aqueous
      solutions of monofructose-amino acids 4-6 generated 0.9-3.6 x 10(-10) M s-1 O2*-
      at pH 7. Surprisingly, the rates of superoxide radical formation in the solutions
      of difructose-amino acids 7-9 were significantly higher (0.75-5.8 x 10(-9) M s-1
      O2*-). The percentage of acyclic sugar anomers (</=0. 8-85%) and their
      "enolization" rate constants (5 x 10(-6) to 2 x 10(-3) s-1) varied broadly for
      the compounds studied and positively correlated with the rates of superoxide
      radical formation. The presence of Cu2+ markedly increased the rate of superoxide
      radical formation at metal concentrations higher than 1 microM, while Fe3+ did
      not accelerate the reaction even at 100 microM. Therefore, in addition to the
      metal ion-catalyzed oxygen free radical formation, metal-free enol oxidation of
      fructosyl groups on glycated amino acid residues may contribute to the generation
      of oxygen free radicals and their subsequent oxidative damage to proteins.

PMID- 10077486
TI  - Synthesis and characterization of polycyclic aromatic hydrocarbon o-quinone
      depurinating N7-guanine adducts.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants which may
      cause cancer and require metabolic activation to exert their carcinogenic
      effects. One pathway of activation involves the dihydrodiol dehydrogenase
      catalyzed oxidation of non-K region trans-dihydrodiols to yield catechols, which
      autoxidize to form reactive o-quinones. As a step toward identifying the spectrum
      of PAH o-quinone-DNA adducts that may form in biological systems, depurinating
      PAH o-quinone-guanine adducts were synthesized. Naphthalene-1,2-dione,
      phenanthrene-1,2-dione, and benzo[a]pyrene-7, 8-dione were reacted with 5 equiv
      of 2'-deoxyguanosine (dGuo) under acidic conditions (1:1 acetic acid/water). The
      products were purified by reversed-phase HPLC, characterized by a combination of
      UV spectroscopy, electrospray ionization/tandem mass spectrometry, and high-field
      proton nuclear magnetic resonance spectroscopy, and identified as 7-(naphthalene
      1,2-dion-4-yl)guanine (MH+, m/z 308), 7-(phenanthrene-1,2-dion-4-yl)guanine (MH+,
      m/z 358), and 7-(benzo[a]pyrene-7,8-dion-10-yl)guanine (MH+, m/z 432),
      respectively. Reaction at N7 of dGuo leads to cleavage of the glycosidic bond,
      producing depurinating adducts. Reaction of phenanthrene-1,2-dione with calf
      thymus DNA led to the formation of the corresponding depurinating adduct. The
      loss of modified bases in DNA generates apurinic sites which, if unrepaired, can
      lead to mutations and thus cellular transformation. These synthesized PAH o
      quinone-N7-guanine adducts can be used as standards to identify such adducts in
      vitro and in vivo.

PMID- 10077487
TI  - Persistence of N7-(2,3,4-trihydroxybutyl)guanine adducts in the livers of mice
      and rats exposed to 1,3-butadiene.
AB  - Liquid chromatography (LC) in combination with tandem mass spectrometry (MS/MS)
      and stable isotope methodology was employed for the analysis of the N7-guanine
      (Gua) adducts derived from 1,2:3, 4-diepoxybutane (BDO2) a reactive metabolite of
      1,3-butadiene (BD). Two diastereomeric forms of N7-(2,3,4-trihydroxybutyl)guanine
      (THBG) were identified in the livers of both mice and rats. One of the
      diastereomers [(+/-)-THBG] was formed by reaction of DNA with (+/-)-BDO2, and the
      other diastereomer (meso-THBG) was formed by reaction of DNA with meso-BDO2.
      There was significantly more (+/-)-THBG and meso-THBG in the liver DNA of the
      mice when compared with those of the rats during the 10 days of exposure to BD
      and the 6 days of postexposure that were monitored. There was a 2-fold excess of
      (+/-)-THBG over meso-THBG in the rat liver at all the time points. In the mouse
      liver after 10 days of exposure to BD, the (+/-)-THBG (3.9 adducts/10(6) normal
      bases) was also present in an almost 2-fold excess over meso-THBG (2.2
      adducts/10(6) normal bases). However, 6-days after exposure to BD, (+/-)-THBG
      (1.2 adducts/10(6) normal bases) and meso-THBG (1.0 adduct/10(6) normal bases)
      were present in almost equal amounts in the mouse liver. Furthermore, there was
      an almost 5-fold excess of the two THBG diastereomers in the mouse liver DNA 6
      days after exposure to BD when compared with rat liver DNA. The half-lives of (+/
      )-THBG and meso-THBG appeared to be slightly longer in mouse liver (4.1 and 5.5
      days, respectively) than in rat liver (3.6 and 4.0 days, respectively). The
      apparent persistence of these adducts in the mouse may contribute to the
      increased susceptibility of this species to BD-induced carcinogenesis. It is
      possible that (+/-)-THBG and meso-THBG could have also been derived from the
      reaction of DNA with the hydrolysis product of BDO2, 1,2-dihydroxy-3,4
      epoxybutane (DHEB). Surprisingly, a vast majority of the studies in which the
      mutagenic and carcinogenic potential of BDO2 have been examined have only
      employed the commercially available (+/-)-BDO2. In light of the present findings,
      additional studies will be required to determine the potency of meso-BDO2 and the
      DHEB that is the precursor to meso-THBG as mutagens and carcinogens.

PMID- 10077488
TI  - Mutational consequences of replication of M13mp7L2 constructs containing cis
      opened benzo[a]pyrene 7,8-diol 9, 10-epoxide-deoxyadenosine adducts.
AB  - The four adducts that arise by cis ring opening of the four optically active
      benzo[a]pyrene diol epoxides by the exocyclic N6-amino group of deoxyadenosine
      were incorporated synthetically into each of two different oligonucleotide 16
      mers, 5'-TTTXGAGTCTGCTCCC-3' [context I(A)] and 5'-CAGXTTTAGAGTCTGC-3' [context
      II(A)], at the X position. The eight resultant oligonucleotides were separately
      ligated into bacteriophage M13mp7L2 and replicated in Escherichia coli that had
      been SOS-induced, and the progeny were analyzed to evaluate the consequences of
      replication past these adducts. The presence of these adducts reduced plaque
      yields substantially. However, the progeny obtained exhibited high frequencies of
      base substitution mutation ranging from 9 to 68%, depending upon the individual
      adduct and the sequence context in which it was placed. For most of the adducts,
      A --> T transversion was the mutation found most frequently in either sequence
      context, and mutation frequencies in context I(A) were always substantially
      greater than those in context II(A). In context I(A), adducts with an R
      configuration at the site of nucleoside attachment were more mutagenic than those
      with an S configuration. In both sequence contexts that were studied, the cis
      adduct arising from the (7S,8R)-diol (9S,10R)-epoxide was the most mutagenic
      adduct. These findings clearly show that individual mutation frequencies are
      determined by the combined effects of both adduct structure and sequence context.

PMID- 10077489
TI  - Function of thioredoxin reductase as a peroxynitrite reductase using
      selenocystine or ebselen.
AB  - The activity of mammalian thioredoxin reductase as a peroxynitrite reductase was
      investigated. Peroxynitrite was infused to maintain a 0.2 microM steady-state
      concentration in potassium phosphate buffer (pH 7.4). Benzoate hydroxylation and
      nitrite formation were used as indices of oxidation reactions of peroxynitrite
      and of peroxynitrite reduction, respectively. In the presence of NADPH (10
      microM), thioredoxin reductase at 50 nM alone did not significantly scavenge
      peroxynitrite, as shown by there being no significant effect on benzoate
      hydroxylation or nitrite formation. However, when selenocystine (1 microM) or
      ebselen (2 microM) was present in the reaction mixture, there was significant
      suppression of benzoate hydroxylation and an increase in nitrite formation until
      all the NADPH was oxidized. The addition of thioredoxin did not enhance these
      effects. In contrast, peroxynitrite reduction by ebselen complexed with BSA was
      enhanced by the presence of thioredoxin. In parallel experiments, thioredoxin
      reductase efficiently reduced ebselen selenoxide back to ebselen.

PMID- 10077490
TI  - Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro.
AB  - The growth-promoting effects of estrogens in hormone-dependent tumor tissues
      involve receptor-mediated pathways that are well-recognized; however, the role of
      estrogens in tumor initiation remains controversial. Estrogen metabolites,
      primarily the catechol estrogens (CE's), have been implicated in tumor initiation
      via a redox cycling mechanism. We have developed metabolically stable CE
      analogues for the study of receptor versus redox cycling effects on DNA damage.
      Comparisons between hydroxy estradiols (HE2's), methoxy estradiols (ME2's), and
      hydroxymethyl estradiols (HME2) in potentiometric and DNA damaging studies were
      made. DNA damage was assessed in calf thymus DNA using 8-oxo-2'-deoxyguanosine (8
      oxo-dG) as a genotoxic marker for oxidative stress. Increases in the number of 8
      oxo-dG/10(5) dG were significant for each 2-HE2 and 4-HE2. Cu(II)SO4, a
      transition metal known to catalyze the redox cycling of o-quinones, substantially
      increased the amount of DNA damage caused by both CE's. However, DNA damage was
      only observed at concentrations of 10 microM or higher, much greater than what is
      found under physiologic conditions. Furthermore, the presence of endogenous
      antioxidants such as glutathione, SOD, and catalase drastically reduced the
      amount of DNA damage induced by high concentrations of 2-HE2. There was no DNA
      damage observed for the non-redox cycling HME2's, making these compounds useful
      probes in the study of receptor-mediated carcinogenesis. Thus, both 2-HE2 and 4
      HE2 are capable of producing oxidative DNA damage at micromolar concentrations in
      vitro. However, since the amount of CE's has not been shown to surpass nanomolar
      levels in vivo, it is unlikely that free radical production via redox cycling of
      CE's is a causative factor in human tumorigenesis.

PMID- 10077491
TI  - Importance of peri-interactions on the stereospecificity of rat hydroxysteroid
      sulfotransferase STa with 1-arylethanols.
AB  - Hydroxysteroid (alcohol) sulfotransferases catalyze the sulfation of polycyclic
      aromatic hydrocarbons (PAHs) that contain benzylic hydroxyl functional groups.
      This metabolic reaction is often a critical step in the activation of a
      hydroxyalkyl-substituted PAH to form an electrophilic metabolite that is capable
      of forming covalent bonds at nucleophilic sites on DNA, RNA, and proteins. Since
      hydroxyalkyl-substituted PAHs are often metabolically formed by the
      stereoselective enzymatic hydroxylation of a benzylic position on an alkyl
      substituted PAH, we have investigated the possibility that the sulfation of
      hydroxyalkyl aromatic hydrocarbons is also stereoselective. Homogeneous
      preparations of rat hepatic hydroxysteroid (alcohol) sulfotransferase STa were
      utilized to investigate the stereoselectivity of its catalytic function with the
      enantiomers of model 1-arylethanols. While only minimal stereoselectivity was
      observed for the catalytic efficiency of STa with the enantiomers of 1-(2
      naphthyl)ethanol and 1-acenaphthenol, the enzyme was stereospecific for (R)-(+)-1
      (1-naphthyl)ethanol, (R)-(+)-1-(1-pyrenyl)ethanol, and (R)-(+)-1-(9
      phenanthryl)ethanol as substrates. Moreover, (S)-(-)-1-(1-naphthyl)ethanol, (S)-(
      )-1-(1-pyrenyl)ethanol, and (S)-(-)- 1-(9-phenanthryl)ethanol were competitive
      inhibitors of STa. Structural and conformational analyses of these 1-arylethanols
      indicated that steric interactions between the substituents on the benzylic
      carbon and the hydrogen in the peri-position on the aromatic ring system were
      important determinants of the stereospecificity of the enzyme with these
      molecules. The findings presented here have implications for the more accurate
      prediction of the ability of hydroxyalkyl-substituted PAHs to be activated via
      metabolic formation of electrophilic sulfuric acid esters.

PMID- 10077492
TI  - Opposite behaviors of reactive metabolites of tienilic acid and its isomer toward
      liver proteins: use of specific anti-tienilic acid-protein adduct antibodies and
      the possible relationship with different hepatotoxic effects of the two
      compounds.
AB  - Tienilic acid (TA) is responsible for an immune-mediated drug-induced hepatitis
      in humans, while its isomer (TAI) triggers a direct hepatitis in rats. In this
      study, we describe an immunological approach developed for studying the
      specificity of the covalent binding of these two compounds. For this purpose, two
      different coupling strategies were used to obtain TA-carrier protein conjugates.
      In the first strategy, the drug was linked through its carboxylic acid function
      to amine residues of carrier proteins (BSA-N-TA and casein-N-TA), while in the
      second strategy, the thiophene ring of TA was attached to proteins through a
      short 3-thiopropanoyl linker, the corresponding conjugates (BSA-S-5-TA and betaLG
      S-5-TA) thus preferentially presenting the 2, 3-dichlorophenoxyacetic moiety of
      the drug for antibody recognition. The BSA-S-5-TA conjugate proved to be 30 times
      more immunogenic than BSA-N-TA. Anti-TA-protein adduct antibodies were obtained
      after immunization of rabbits with BSA-S-5-TA (1/35000 titer against betaLG-S-5
      TA in ELISA). These antibodies strongly recognized the 2, 3-dichlorophenoxyacetic
      moiety of TA but poorly the part of the drug engaged in the covalent binding with
      the proteins. This powerful tool was used in immunoblots to compare TA or TAI
      adduct formation in human liver microsomes as well as on microsomes from yeast
      expressing human liver cytochrome P450 2C9. TA displayed a highly specific
      covalent binding focused on P450 2C9 which is the main cytochrome P450
      responsible for its hepatic activation in humans. On the contrary, TAI showed a
      nonspecific alkylation pattern, targeting many proteins upon metabolic
      activation. Nevertheless, this nonspecific covalent binding could be completely
      shifted to a thiol trapping agent like GSH. The difference in alkylation patterns
      for these two compounds is discussed with regard to their distinct toxicities. A
      relationship between the specific covalent binding of P450 2C9 by TA and the
      appearance of the highly specific anti-LKM2 autoantibodies (known to specifically
      recognize P450 2C9) in patients affected with TA-induced hepatitis is strongly
      suggested.

PMID- 10077493
TI  - C8-Arylguanine and C8-aryladenine formation in calf thymus DNA from
      arenediazonium ions.
AB  - Arylhydrazides, arylhydrazines, and N-alkyl-N-arylnitrosamines are metabolized to
      arenediazonium ions which yield C8-arylpurine adducts in calf thymus and cellular
      DNA. The mechanism of adduct formation has not been fully elucidated. C8
      Arylguanine adducts likely form from direct aryl radical (Ar*) addition to the C8
      position of guanine. However, the amounts of C8-aryladenine adducts measured here
      are inconsistent with direct radical attack at the C8 position of adenine. An
      intermediate product, an aryltriazene, is likely formed which then decomposes to
      the C8-aryladenine adduct. We have demonstrated that N1-aryl-N3-purinyltriazene
      adducts are formed from a variety of para-substituted arenediazonium ions with
      adenine. Decomposition of the N1-aryl-N3-purinyltriazene, at high pH and elevated
      temperatures, has been shown to give C8-aryladenine derivatives, and a free
      radical mechanism for this process has been proposed. Here we show that this
      process can occur under physiological conditions and that the C8-aryladenine
      adduct can be quantitated by HPLC. ESR studies, in which DMPO was used as a spin
      trap, have been used to demonstrate the intermediacy of aryl radicals during the
      decomposition of the N1-aryl-N3-purinyltriazenes and to demonstrate that this
      process also occurs in calf thymus (ct) DNA treated with arenediazonium ions.
      These results suggest the involvement of an aryl radical in the formation of the
      observed DNA adducts. Finally, we have found that the treatment of ct DNA with
      arenediazonium ions produces a significant amount of depurination. Both the
      formation of C8-arylguanine and C8-aryladenine adducts and the generation of
      apurinic sites may contribute to the genotoxicity of arylhydrazides,
      arylhydrazines, N-alkyl-N-arylnitrosamines, and arenediazonium ions.

PMID- 10077494
TI  - Anatomical and developmental study of petrified Quercus (Fagaceae) fruits from
      the Middle Miocene, Yakima Canyon, Washington, USA.
AB  - The first reported petrified acorns to show internal anatomical structure are
      here described from Middle Miocene (~15.6 million years old) chert of the
      Columbia River Basalt Group in Yakima Canyon, Washington. Quercus hiholensis
      Borgardt et Pigg sp. nov. is described from anatomical and morphological fruit
      features, as well as a little recognized anatomical feature, the umbilical
      complex. Acorns, each comprising a nut and its cupule, are up to 15.3 mm long and
      18.8 mm wide with helically arranged, imbricate, tuberculate cupule scales. They
      show basal aborted ovules, short styles, broad stigmas, and lack grooves in their
      cotyledons. These characters and the developmental pattern seen in these fossil
      acorns demonstrate that Q. hiholensis conforms to genus Quercus (Fagaceae),
      subgenus Quercus, section Quercus (the white oaks). The correspondence of Q.
      hiholensis to the modern section Quercus reveals that the derived floral and
      fruit characters that distinguish section Quercus within the genus had evolved by
      the Middle Miocene.

PMID- 10077495
TI  - A new Bennettitalean trunk with unilacunar five-trace nodal structure from the
      Upper Cretaceous of Hokkaido, Japan.
AB  - A new species of Bucklandia is described based on a permineralized fossil trunk
      that was obtained from sediments of Upper Cretaceous age from Hokkaido, Japan.
      The quality of preservation is exquisite, and anatomical and morphological
      features are preserved at the cellular level. The specimen is clearly
      bennettitalean because of the cycadeoidean-type arrangement of vascular bundles
      in the petiole. However, this specimen is unique among previously described
      progymnosperms and gymnosperms in possessing a unilacunar five-trace type of
      nodal structure. The fossil thus contributes to a more complete understanding of
      the variation of nodal structure in bennettitalean trunks.

PMID- 10077496
TI  - Variation among populations of Clarkia Unguiculata (Onagraceae) along altitudinal
      and latitudinal gradients.
AB  - We investigated phenotypic variation in 15 traits in greenhouse-grown plants from
      16 populations of Clarkia unguiculata from three elevational habitats and six
      latitudinal transects. Populations from the lowest and highest elevations were
      geographically and ecologically marginal within the species' range. We (1)
      describe patterns of trait variation with elevation and latitude; (2) compare
      latitutidinal variation between marginal and central areas of the species' range;
      and (3) compare patterns of variation within C. unguiculata to interspecific
      patterns within the genus. Although there was some evidence that traits varied
      clinally (i.e., increased/decreased monotonically) along environmental gradients,
      interaction effects between altitude and latitude dominated patterns of
      variation. For most traits, latitudinal trends at the low-elevation margin of the
      species' range differed from trends at mid- and high-elevation areas. Based on
      interspecific comparisons, populations at the hotter, more arid ends of both
      environmental gradients were expected to have rapid development, small flowers
      and vegetative size, low levels of herkogamy and protandry, and high rates of gas
      exchange. Instead, we found that while some traits were correlated with one
      gradient in the expected way (e.g., development time with elevation, gas-exchange
      physiology with latitude), all traits were not consistently associated with each
      other along both gradients, and intraspecific patterns of variation differed from
      interspecific patterns.

PMID- 10077497
TI  - Genetic diversity and structure of the narrow endemic Wyethia reticulata and its
      congener W. bolanderi (Asteraceae) using RAPD and allozyme techniques.
AB  - Wyethia reticulata is an edaphic endemic in the Sierra Nevada foothills. Its
      sympatric congener, W. bolanderi, is also restricted to the foothills, but has a
      north-south range of 275 km, compared to 14 km for W. reticulata. The goals of
      this study were to determine clonal diversity, population size, genetic
      variation, and spatial and generic structure for each species from paired
      populations in El Dorado County, California, using allozyme and RAPD (random
      amplified polymorphic DNA) methodologies. Wyethia reticulata, spreading by
      rhizomes, had populations dominated by a few large individuals, while W.
      bolanderi, with a basal caudex, had populations of a few hundred evenly sized
      individuals. Genetic analyses indicated that W. reticulata, compared to its
      congener, had somewhat less genetic diversity (H(T): 0.28 vs. 0.38), had more of
      its genetic variation partitioned among populations (F(ST): 0.25 vs. 0.07), and
      showed a complete absence of inbreeding (F(IS): -0.03 vs. 0.22). Population
      membership in accord with populations defined by geographical location resulted
      only when all markers were included in the analysis. Ecological limits on
      recruitment of genets appears to result in small population size in W.
      reticulata. Limited gene flow, drift within small populations, and sexual
      reproductive dominance of large clones result in the genetic divergence of
      populations in this species, while genetic diversity is maintained by the
      longevity of clones and outbreeding.

PMID- 10077498
TI  - Floral development and the formation of unisexual spikelets in the Andropogoneae
      (Poaceae).
AB  - We investigated spikelet development in four distantly related species of the
      grass tribe Andropogoneae to determine whether spikelet development and the
      formation of unisexual florets are uniform throughout the tribe. We studied
      development in Bothriochloa bladhii, Coelorachis aurita, Heteropogon contortus,
      and Hyparrhenia hirta, and compared these with Panicum, a member of the sister
      tribe Paniceae. Many aspects of spikelet development in the species we have
      studied correlate with what is already known for Tripsacum and maize (both
      Andropogoneae), despite variation in how unisexual florets are distributed on the
      plant. The formation of unisexual spikelets is also uniform. All florets initiate
      both pistil and stamen primordia. In florets destined to be male, cell death
      occurs in the subepidermal layers of the gynoecium after the formation of a
      gynoecial ridge. In florets destined to be female, there is no apparent cell
      death in the stamens, but growth ceases after anther formation. The similarity in
      spikelet development and the formation of unisexual florets point to a common
      genetic mechanism for sex determination throughout the Andropogoneae and possibly
      the entire Panicoideae. Use of a cell death pathway to cause gynoecial abortion
      may be the basis of one morphological character that defines the subfamily.

PMID- 10077499
TI  - Effects of environmental factors on development of wood.
AB  - This research tested the hypothesis that environmental factors (light, water, and
      nutrient levels) affect wood development. Specimens were placed in treatments of
      low, medium, or high levels of light, water, nitrogen, or phosphorus for one
      year. Control plants received medium levels of all factors, while experimental
      plants received medium levels of all factors except the experimental factor; for
      example, "high light" treatment consisted of high light but medium levels of
      water, nitrogen, and phosphorus. Some character changes seen in Cereus peruvianus
      were a reduction in mean vessel diameter and shoot elongation as a result of low
      nitrogen and low phosphorus treatments and a reduction in mean vessel density due
      to low light; high water induced broader vessels and greater shoot elongation. In
      Cereus tetragonus, low water treatment caused a reduction in mean vessel
      diameter, and high nitrogen decreased the amount of wood produced. Whereas all
      characters studied showed a significant correlation with at least one treatment
      in one species, few characters responded similarly between species. Estimated
      specific conductivity of wood could be altered by treatments affecting either
      vessel density or vessel diameter strongly or by treatments affecting both
      diameter and density weakly. Under the conditions tested, wood structure was
      stable but estimated conducting capacity was more flexible.

PMID- 10077500
TI  - Phylogenetic relationships of land plants using mitochondrial small-subunit rDNA
      sequences.
AB  - Phylogenetic relationships among embryophytes (tracheophytes, mosses, liverworts,
      and hornworts) were examined using 21 newly generated mitochondrial small-subunit
      (19S) rDNA sequences. The "core" 19S rDNA contained more phylogenetically
      informative sites and lower homoplasy than either nuclear 18S or plastid 16S
      rDNA. Results of phylogenetic analyses using parsimony (MP) and likelihood (ML)
      were generally congruent. Using MP, two trees were obtained that resolved either
      liverworts or hornworts as the basal land plant clade. The optimal ML tree showed
      hornworts as basal. That topology was not statistically different from the two MP
      trees, thus both appear to be equally viable evolutionary hypotheses. High
      bootstrap support was obtained for the majority of higher level embryophyte
      clades named in a recent morphologically based classification, e.g.,
      Tracheophyta, Euphyllophytina, Lycophytina, and Spermatophytata. Strong support
      was also obtained for the following monophyletic groups: hornworts, liverworts,
      mosses, lycopsids, leptosporangiate and eusporangiate ferns, gymnosperms and
      angiosperms. This molecular analysis supported a sister relationship between
      Equisetum and leptosporangiate ferns and a monophyletic gymnosperms sister to
      angiosperms. The topologies of deeper clades were affected by taxon inclusion
      (particularly hornworts) as demonstrated by jackknife analyses. This study
      represents the first use of mitochondrial 19S rDNA for phylogenetic purposes and
      it appears well-suited for examining intermediate to deep evolutionary
      relationships among embryophytes.

PMID- 10077501
TI  - Chromosomes of villadia and altamiranoa (crassulaceae).
AB  - Villadia, ranging from Texas to Peru with some 25 species, has a rather
      distinctive thyrsoid to spicate inflorescence, and we keep it as a genus separate
      from Sedum. Twenty species show every gametic chromosome number from 9 to 17 and
      also 20-22 and higher. Chromosome pairing in hybrids shows that the species
      differ by many translocations and that species with 21 or lower are effectively
      diploid. More specialized species tend to have fewer and larger chromosomes,
      suggesting that through time translocations have rearranged the ancestral genome
      into fewer units. We suspect that relocated genes may be programmed differently,
      affecting phenotype. Thus Villadia is like Echeveria in having a remarkably long
      descending series of evidently diploid chromosome numbers. Altamiranoa, often
      included in Villadia, with about 15 species from Mexico south, more closely
      resembles Sedum in its broadly cymose inflorescence. It appears polyphyletic,
      with no clear boundary from Sedum, and we disperse its species in Sedum. The ten
      species studied have gametic numbers from 20 to 29 that probably are effectively
      diploid, with a few higher and probably polyploid. Again, chromosome pairing in
      hybrids shows that the species differ by many translocations. Putative relatives
      in Sedum section Leptosedum have n = 26 to 31. Thus cytologically as well as
      morphologically Altamiranoa has remained more similar than Villadia to its Sedum
      relatives.

PMID- 10077502
TI  - ITS sequence data support a single origin for North American Astereae
      (Asteraceae) and reflect deep geographic divisions in Aster s.l.
AB  - The Astereae is the largest tribe of Asteraceae in North America. Morphological
      diversity suggests that the North American assemblage is polyphyletic as 12
      endemic genera, as well as lineages of the genus Erigeron and Conyza (Conyzinae),
      have been hypothesized to represent at least five separate invasions of North
      America from Africa, Australia, Eurasia, and South America. This hypothesis was
      tested with a phylogenetic analysis of nucleotide sequence data from the internal
      transcribed spacers (ITS) of nuclear ribosomal DNA. Sequences for 62 taxa
      represent seven outgroup taxa and all major Northern and Southern Hemisphere
      groups of Astereae, including broad taxonomic and geographic sampling of
      Conyzinae and Aster s.l. (sensu lato). Parsimony analyses indicate that all North
      American Astereae are members of a strongly supported clade, and that a diverse
      group of predominantly woody taxa from Africa, Australia, and South America, are
      basal Astereae. Furthermore, Aster s.l. is deeply polyphyletic as Eurasian taxa,
      including Aster s.s. (sensu stricto), appear more closely related to Southern
      Hemisphere taxa than to North American Aster segregates. There is only low to
      moderate agreement between proposed higher level Astereae relationships based on
      ITS and those based either on morphology or chloroplast restriction site data.

PMID- 10077503
TI  - Phylogenetic relationships of subtribe Ecliptinae (Asteraceae: Heliantheae) based
      on chloroplast DNA restriction site data.
AB  - Phylogenetic analysis of chloroplast DNA restriction site data for 76 of the 302
      genera of Heliantheae sensu lato using 16 restriction endonucleases reveals that
      subtribe Ecliptinae is polyphyletic and that its genera are distributed in four
      different lineages. The ecliptinous genera Squamopappus, Podachaenium, Verbesina,
      and Tetrachyron (of the Neurolaeninae), along with other members of subtribe
      Neurolaeninae are the basalmost clades of the paleaceous Heliantheae. The mostly
      temperate species of subtribe Ecliptinae (exemplified by Balsamorhiza, Borrichia,
      Chrysogonum, Engelmannia, Silphium, Vigethia, and Wyethia) are strongly nested in
      a clade with the Mesoamerican monotypic genus Rojasianthe as basal. The genera
      characterized by marcescent ray corollas traditionally classified in subtribe
      Zinniinae constitute a strongly supported group sister to Acmella, Spilanthes,
      and Salmea. The largest clade of ecliptinous genera is the most recently derived
      group within Heliantheae sampled. This large group of mostly Neotropical lowland
      genera (variously characterized by their winged cypselae, foliaceous phyllaries,
      and opposite phyllotaxy and exemplified by Perymenium, Wedelia, and Zexmenia) has
      been and continues to be the most challenging group from a taxonomic standpoint.
      The study provides new insights as to their relationships that will have a
      positive impact in future monographic studies of the group. The genera of the
      Espeletiinae form a monophyletic clade and are sister to members of the
      Milleriinae and Melampodiinae. This result is consistent with their traditional
      taxonomic placement with genera such as Smallanthus with which they share a
      tendency for functionally staminate disc flowers. The phylogenetically enigmatic
      genus Montanoa is sister to Melampodium. Members of subtribe Galinsoginae are
      clustered in two main lineages that correspond to the traditional division of the
      subtribe based on pappus characteristics. There is no support for the monophyly
      of subtribe Galinsoginae, and the same results indicate some of its genera are
      paraphyletic.

PMID- 10077504
TI  - The status of Clarkia australis (Onagraceae).
AB  - Clarkia australis and C. virgata grow on the western slope of the central Sierra
      Nevada of California. Clarkia australis was established to accommodate
      populations of C. virgata from south of the Tuolumne River that could not be
      successfully hybridized to populations north of the river. Although the species
      is maintained in the new Jepson Manual, its validity has been questioned because
      only two populations were originally tested, and they had no useful morphological
      traits that distinguished them from C. virgata. We report here the results of a
      large program of interpopulation hybridizations that show that C. australis is
      distinct and that its reproductive isolation from C. virgata is complete and
      absolute and reflects a compatibility block that apparently causes abortion of
      hybrid seeds in early development. Both species include populations north and
      south of the Tuolumne River and, in general, those of C. australis occupy higher
      elevations. Morphologically, the species are extremely similar though the mean
      values of several dimensions of the petals are different. However, significant
      variation among their populations has the consequence that, at present, the only
      certain way to assign particular populations to species is to test their
      compatibility with previously tested populations.

PMID- 10077505
TI  - Variation of breeding system, floral rewards, and reproductive success in clonal
      Calystegia species (Convolvulaceae).
AB  - The reproductive biology of four Japanese Calystegia species (Convolvulaceae) was
      studied to examine the effects of clonality and population structure on
      reproductive success. Calystegia soldanella, C. hederacea, and C. japonica are
      self-incompatible, while C. sepium is self-compatible but needs pollinator
      services for self-pollination. The showy, bisexual flowers of Calystegia offer
      pollen and nectar that attract many kinds of insects such as bees and syrphid
      flies. Clones of C. soldanella often formed mats just above the high tide line on
      beaches and produced a great number of seeds. Calystegia hederacea and C.
      japonica were distributed as patches of separate clones and often failed to
      transfer pollen grains among clones. Fruit and seed sets in C. hederacea and C.
      japonica were not limited by pollinators but by the number of compatible pollen
      grains. Although C. sepium clones were also distributed in patches, high and
      stable fecundity was achieved by self-compatibility and pollinator attraction. We
      suggest that self-compatibility in C. sepium has evolved under fertilization
      limitation caused by geitonogamy or facilitated selfing.

PMID- 10077506
TI  - Foliar nitrogen and phosphorus dynamics of three Chilean Nothofagus (Fagaceae)
      species in relation to leaf lifespan.
AB  - This study examined foliar nutrient dynamics and nutrient resorption
      (retranslocation) in three species of Chilean Nothofagus (Fagaceae) that differed
      in leaf lifespan and elevational distribution. In our central Chile study area
      the elevations at which these three species are most abundant increase from N.
      obliqua (deciduous) at low elevations to N. dombeyi at intermediate elevation and
      N. pumilio (deciduous) at higher elevations up to treeline. We sampled a single
      stand at 1680 m in which all three species co-occurred. Nothofagus dombeyi leaves
      were structurally heavier, with specific leaf mass approximately twice that of
      the two deciduous species. On a concentration basis, foliar N increased in the
      order N. dombeyi < N. pumilio < N. obliqua and foliar P increased in the order N.
      dombeyi < N. obliqua < N. pumilio. However, when the differences in specific leaf
      mass among species were taken into account by calculating N and P content on a
      leaf area basis, N. dombeyi had the greatest N and P content. N and P remained
      relatively constant throughout most of the 4-yr N. dombeyi leaf lifespan, then
      decreased prior to abscission. Nothofagus dombeyi resorbed significantly less N
      (44-50%) than did the two deciduous species (63-78%), both on proportional and
      absolute bases. In contrast, N. pumilio and N. dombeyi resorbed similar amounts
      of P prior to abscission (40-50%), whereas no significant resorption of P from
      leaves of N. obliqua was noted. We use these results to clarify the relative
      importance of environmental gradients associated with elevation vs. genetically
      fixed leaf lifespans in controlling the nutrient dynamics of these congeneric
      tree species.

PMID- 10077507
TI  - FDA panel votes against approval for bivalirudin.

PMID- 10077508
TI  - Cytomegalovirus infection and coronary restenosis.

PMID- 10077509
TI  - Acute pulmonary thromboembolism: has its evolution been redefined?

PMID- 10077510
TI  - Tenascin-C is expressed in macrophage-rich human coronary atherosclerotic plaque.
AB  - BACKGROUND: Tenascin is a large extracellular matrix glycoprotein generally found
      in adult tissues undergoing active remodeling such as healing wounds and tumors.
      To determine the potential role of tenascin-C (TN-C) in the pathophysiology of
      atherosclerosis, we investigated the pattern of expression of TN-C in human
      coronary atherosclerotic plaques. METHODS AND RESULTS: Immunohistochemical
      staining and in situ hybridization demonstrated minimal and random expression of
      TN-C in fibrotic but lipid-poor atherosclerotic plaques. In contrast, all plaques
      with an organized lipid core or ruptured intimal surface strongly expressed TN-C,
      which was preferentially concentrated around the lipid core, shoulder regions,
      and ruptured area of the plaques but not in the fibrous cap. TN-C was not
      detected in normal arterial tissue. To identify the cellular source of TN-C, the
      plaques were stained with smooth muscle cell- and macrophage-specific antibodies.
      TN-C expression correlated with the infiltration of macrophages. Northern blot
      and immunoprecipitation analysis showed that macrophages expressed 7. 0-kb TN-C
      mRNA and 220-kDa protein. Reverse transcription-polymerase chain reaction of
      total RNA derived from macrophages showed that they express the small isoform of
      TN-C. Zymogram analysis revealed that macrophages markedly increased MMP-9
      expression. CONCLUSIONS: This study demonstrates that the level of TN-C
      expression correlates with the degree of inflammation present, not with plaque
      size. In addition, cultured macrophages have the capacity to express the TN-C
      gene. These findings suggest the significance of macrophages in the remodeling of
      atherosclerotic plaque matrix composition.

PMID- 10077511
TI  - Prior cytomegalovirus infection and the risk of restenosis after percutaneous
      transluminal coronary balloon angioplasty.
AB  - BACKGROUND: Restenosis is a common problem after all revascularization procedures
      in atherosclerotic coronary arteries. Reactivated human cytomegalovirus (CMV) has
      been detected in tissues of restenotic vascular lesions and was hypothesized to
      be a contributing pathogenic factor. Recent data suggest an association of
      restenosis after optimal coronary atherectomy with CMV serostatus, and a possible
      role of antiviral therapy was discussed. We therefore tested the hypothesis that
      prior CMV infection might be a risk factor for restenosis after conventional
      coronary balloon angioplasty (PTCA). METHODS AND RESULTS: We analyzed 92
      consecutive patients who had been admitted for control angiography after previous
      PTCA within a mean interval of 6 months. Anti-CMV antibodies were measured as an
      indicator of prior CMV infection and latency. The coronary angiograms before
      PTCA, directly after, and 6 months later were analyzed quantitatively. Sixty-five
      percent of the patients were CMV-positive. Before PTCA, the degree (mean+/-SD) of
      stenosis was 69+/-10% in CMV-positive and 68+/-8.3% in CMV-negative subjects.
      PTCA resulted in a residual stenosis of 39% in both groups. After 6 months, the
      late losses of luminal diameter in the CMV-positive and -negative groups were
      11+/-13% and 12+/-15%, respectively (P=0.658). In an ANCOVA with 25 potential
      risk factors for restenosis, CMV serostatus was not significantly associated with
      restenosis development. CONCLUSIONS: Our data indicate that prior CMV infection,
      in contrast to optimal atherectomy, is not associated with chronic restenosis
      after conventional coronary balloon angioplasty. The results do not support a
      possible benefit from antiviral therapy.

PMID- 10077512
TI  - Global biventricular dysfunction in patients with asymptomatic coronary artery
      disease may be caused by myocarditis.
AB  - BACKGROUND: The causal role of asymptomatic critical coronary artery obstruction
      in patients presenting with severe global biventricular dysfunction but no
      evidence of myocardial infarction is uncertain. METHODS AND RESULTS: Among 291
      patients aged >40 years undergoing a noninvasive (2-dimensional echocardiography)
      and invasive (catheterization, coronary angiography, and biventricular
      endomyocardial biopsy, 6 to 8 samples/patient) cardiac study because of
      progressive heart failure (New York Heart Association functional class III or IV)
      with global biventricular dysfunction and no history of myocardial ischemic
      events, 7 patients (2.4%; 7 men; mean age, 49+/-6.9 years) had severe coronary
      artery disease (3 vessels in 4 patients; 2 vessels in 1 patient, proximal
      occlusion of left anterior descending coronary artery in 2 patients). Left
      ventricular end-diastolic diameter and ejection fraction by 2-dimensional
      echocardiography were 73+/-10.5 mm and 23+/-6.5%, respectively, and right
      ventricular end-diastolic diameter and ejection fraction were 39+/-7 mm and 29+/
      7.2%, respectively. Biopsy specimens showed extensive lymphocytic infiltrates
      with focal myocytolysis meeting the Dallas criteria for myocarditis in all
      patients (in 5 patients with and 2 patients without fibrosis). Cardiac
      autoantibodies were detected with indirect immunofluorescence in the serum of 2
      patients with active myocarditis. The 2 patients with active inflammation
      received prednisone (1 mg. kg-1. d-1 for 4 weeks followed by 0.33 mg. kg-1. d-1
      for 5 months) and azathioprine (2 mg. kg-1. d-1 for 5 months) in addition to
      conventional drug therapy for heart failure. At 8-month overall follow-up,
      cardiac volume and function improved considerably in immunosuppressed patients
      but remained unchanged in conventionally treated patients, of whom 1 died.
      CONCLUSIONS: Global biventricular dysfunction in patients with severe
      asymptomatic coronary artery disease and no evidence of previous myocardial
      infarction may be caused by myocarditis. Histologic findings may influence the
      treatment.

PMID- 10077513
TI  - Clinical application of an integrated 3-phase mapping technique for localization
      of the site of origin of idiopathic ventricular tachycardia.
AB  - BACKGROUND: Radiofrequency (RF) catheter ablation provides curative treatment for
      idiopathic ventricular tachycardia (VT). METHODS AND RESULTS: Nineteen
      consecutive patients with an idiopathic VT underwent RF catheter ablation. An
      integrated 3-phase mapping approach was used, consisting of the successive
      application of online 62-lead body surface QRS integral mapping, directed
      regional paced body surface QRS integral mapping, and local activation sequence
      mapping. Mapping phase 1 was localization of the segment of VT origin by
      comparing the VT QRS integral map with a database of mean paced QRS integral
      maps. Mapping phase 2 was body surface pace mapping during sinus rhythm in the
      segment localized in phase 1 until the site at which the paced QRS integral map
      matched the VT QRS integral map was identified (ie, VT exit site). Mapping phase
      3 was local activation sequence mapping at the circumscribed area identified in
      phase 2 to identify the site with the earliest local endocardial activation (ie,
      site of VT origin). This site became the ablation target. Ten VTs were ablated in
      the right ventricular outflow tract, 2 at the basal LV septum, and 7 at the
      midapical posterior left ventricle. A high long-term ablation success (mean
      follow-up duration, 14+/-9 months) was achieved in 17 of the 19 patients (89%)
      with a low number of RF pulses (mean, 3.3+/-2.2 pulses per patient). CONCLUSIONS:
      This prospective study shows that integrated 3-phase mapping for localization of
      the site of origin of idiopathic VT offers efficient and accurate localization of
      the target site for RF catheter ablation.

PMID- 10077514
TI  - LocaLisa: new technique for real-time 3-dimensional localization of regular
      intracardiac electrodes.
AB  - BACKGROUND: Estimation of the 3-dimensional (3D) position of ablation electrodes
      from fluoroscopic images is inadequate if a systematic lesion pattern is required
      in the treatment of complex arrhythmogenic substrates. METHODS AND RESULTS: We
      developed a new technique for online 3D localization of intracardiac electrodes.
      Regular catheter electrodes are used as sensors for a high-frequency
      transthoracic electrical field, which is applied via standard skin electrodes. We
      investigated localization accuracy within the right atrium, right ventricle, and
      left ventricle by comparing measured and true interelectrode distances of a
      decapolar catheter. Long-term stability was analyzed by localization of the most
      proximal His bundle before and after slow pathway ablation. Electrogram
      recordings were unaffected by the applied electrical field. Localization data
      from 3 catheter positions, widely distributed within the right atrium, right
      ventricle, or left ventricle, were analyzed in 10 patients per group. The
      relationship between measured and true electrode positions was highly linear,
      with an average correlation coefficient of 0.996, 0.997, and 0.999 for the right
      atrium, right ventricle, and left ventricle, respectively. Localization accuracy
      was better than 2 mm, with an additional scaling error of 8% to 14%. After 2
      hours, localization of the proximal His bundle was reproducible within 1.4+/-1.1
      mm. CONCLUSIONS: This new technique enables accurate and reproducible real-time
      localization of electrode positions in cardiac mapping and ablation procedures.
      Its application does not distort the quality of electrograms and can be applied
      to any electrode catheter.

PMID- 10077515
TI  - Induction of neurally mediated syncope with adenosine.
AB  - BACKGROUND: Tilt testing is used to establish the diagnosis of neurally mediated
      syncope. However, applicability of the tilt test is limited by test sensitivity
      and length of time required to perform the test. We hypothesized that adenosine
      could facilitate the induction of neurally mediated syncope through its
      sympathomimetic effects and therefore could be used as an alternative to routine
      tilt testing. METHODS AND RESULTS: In protocol 1, the yield of adenosine tilt
      testing (12 mg while upright, followed by 60 degrees tilt for 5 minutes) and a 15
      minute isoproterenol tilt test were compared in 84 patients with a negative 30
      minute drug-free tilt test. In protocol 2, 100 patients underwent an initial
      adenosine tilt test followed by our routine tilt test (30-minute drug-free tilt
      followed by a 15-minute isoproterenol tilt). Six additional control patients
      underwent microneurography of the peroneal nerve to compare the sympathomimetic
      effects during bolus administration of adenosine and continuous infusion of
      isoproterenol. In protocol 1, the yields of adenosine (8 of 84, 10%) and
      isoproterenol (7 of 84, 8%) tilt testing were comparable (P=NS). In protocol 2,
      the yields of adenosine (19 of 100, 19%) and routine (22 of 100, 22%) tilt
      testing were also comparable (P=NS). Although the yield of adenosine tilt testing
      was comparable in both protocols, patients with a negative adenosine tilt test
      but a positive routine tilt test usually required isoproterenol to elicit the
      positive response. Microneurography confirmed discordant sympathetic activation
      after adenosine and isoproterenol administration. CONCLUSIONS: Adenosine is
      effective for the induction of neurally mediated syncope, with a diagnostic yield
      comparable to routine tilt testing. However, the discordant results obtained with
      adenosine and the isoproterenol phase of routine tilt testing suggest that
      adenosine and isoproterenol tilt testing may have complementary roles in
      eliciting a positive response. Therefore, a tilt protocol that uses an initial
      adenosine tilt followed, if necessary, by an isoproterenol tilt would be expected
      to increase the overall yield and reduce the duration of tilt testing.

PMID- 10077516
TI  - Pulmonary embolism: one-year follow-up with echocardiography doppler and five
      year survival analysis.
AB  - BACKGROUND: The long-term prognosis for patients with pulmonary embolism (PE) is
      dependent on the underlying disease, degree of pulmonary hypertension (PH), and
      degree of right ventricular (RV) dysfunction. A precise description of the time
      course of pulmonary artery pressure (PAsP)/RV function is therefore of importance
      for the early identification of persistent PH/RV dysfunction in patients treated
      for acute PE. Other objectives were to identify variables associated with
      persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients
      alive 1 month after inclusion. METHODS AND RESULTS: Echocardiography Doppler was
      performed in 78 patients with acute PE at the time of diagnosis and repeatedly
      during the next year. A 5-year survival analysis was made. The PAsP decreased
      exponentially until the beginning of a stable phase, which was </=38 days. The
      recovery of RV function occurred during the same time period. Risk factors for
      persistent PH/RV dysfunction and the 5-year mortality rate were analyzed using
      multiple logistic regression models. A PAsP of >50 mm Hg at the time of diagnosis
      of acute PE was associated with persistent PH after 1 year. The 5-year mortality
      rate was associated with underlying disease. Only patients with persistent PH in
      the stable phase required pulmonary thromboendarterectomy within 5 years.
      CONCLUSIONS: An echocardiography Doppler investigation performed 6 weeks after
      diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and
      may be of value in planning the follow-up and care of these patients.

PMID- 10077517
TI  - Intimal tear without hematoma: an important variant of aortic dissection that can
      elude current imaging techniques.
AB  - BACKGROUND: The modern imaging techniques of transesophageal echocardiography,
      CT, and MRI are reported to have up to 100% sensitivity in detecting the classic
      class of aortic dissection; however, anecdotal reports of patient deaths from a
      missed diagnosis of subtle classes of variants are increasingly being noted.
      METHODS AND RESULTS: In a series of 181 consecutive patients who had ascending or
      aortic arch repairs, 9 patients (5%) had subtle aortic dissection not diagnosed
      preoperatively. All preoperative studies in patients with missed aortic
      dissection were reviewed in detail. All 9 patients (2 with Marfan syndrome, 1
      with Takayasu's disease) with undiagnosed aortic dissection had undergone >/=3
      imaging techniques, with the finding of ascending aortic dilatation (4.7 to 9 cm)
      in all 9 and significant aortic valve regurgitation in 7. In 6 patients, an
      eccentric ascending aortic bulge was present but not diagnostic of aortic
      dissection on aortography. At operation, aortic dissection tears were limited in
      extent and involved the intima without extensive undermining of the intima or an
      intimal "flap." Eight had composite valve grafts inserted, and all survived. Of
      the larger series of 181 patients, 98% (179 of 181) were 30-day survivors.
      CONCLUSIONS: In patients with suspected aortic dissection not proven by modern
      noninvasive imaging techniques, further study should be performed, including
      multiple views of the ascending aorta by aortography. If patients have an
      ascending aneurysm, particularly if eccentric on aortography and associated with
      aortic valve regurgitation, an urgent surgical repair should be considered, with
      excellent results expected.

PMID- 10077518
TI  - Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency
      causing pediatric cardiomyopathy and sudden death.
AB  - BACKGROUND: Genetic defects are being increasingly recognized in the etiology of
      primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD)
      catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism,
      the crucial pathway for cardiac energy production. METHODS AND RESULTS: We
      studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction,
      skeletal myopathy, or sudden death in infancy with hepatic steatosis, features
      suggestive of fatty acid oxidation disorders. Single-stranded conformational
      variance was used to screen genomic DNA. DNA sequencing and mutational analysis
      revealed 21 different mutations on the VLCAD gene in 18 patients. Of the
      mutations, 80% were associated with CM. Severe CM in infancy was recognized in
      most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA
      blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in
      patients with frame-shift or splice-site mutations and absent or severe reduction
      in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical
      phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are
      heterogeneous. Although mortality at presentation is high, both the metabolic
      disorder and cardiomyopathy are reversible.

PMID- 10077519
TI  - Homozygous deletion in KVLQT1 associated with Jervell and Lange-Nielsen syndrome.
AB  - BACKGROUND: Long-QT (LQT) syndrome is a cardiac disorder that causes syncope,
      seizures, and sudden death from ventricular arrhythmias, specifically torsade de
      pointes. Both autosomal dominant LQT (Romano-Ward syndrome) and autosomal
      recessive LQT (Jervell and Lange-Nielsen syndrome, JLNS) have been reported.
      Heterozygous mutations in 3 potassium channel genes, KVLQT1, KCNE1 (minK), and
      HERG, and the cardiac sodium channel gene SCN5A cause autosomal dominant LQT.
      Autosomal recessive LQT, which is associated with deafness, has been found to
      occur with homozygous mutations in KVLQT1 and KCNE1 in JLNS families in which QTc
      prolongation was inherited as a dominant trait. METHODS AND RESULTS: An Amish
      family with clinical evidence of JLNS was analyzed for mutations by use of single
      strand conformation polymorphism and DNA sequencing analyses for mutations in all
      known LQT genes. A novel homozygous 2-bp deletion in the S2 transmembrane segment
      of KVLQT1 was identified in affected members of this Amish family in which both
      QTc prolongation and deafness were inherited as recessive traits. This deletion
      represents a new JLNS-associated mutation in KVLQT1 and has deleterious effects
      on the KVLQT1 potassium channel, causing a frameshift and the truncation of the
      KVLQT1 protein. In contrast to previous reports in which LQT was inherited as a
      clear dominant trait, 2 parents in the JLNS family described here have normal QTc
      intervals (0.43 and 0.44 seconds, respectively). CONCLUSIONS: A novel homozygous
      KVLQT1 mutation causes JLNS in an Amish family with deafness that is inherited as
      an autosomal recessive trait.

PMID- 10077520
TI  - Detection of adenoviral genome in the myocardium of adult patients with
      idiopathic left ventricular dysfunction.
AB  - BACKGROUND: The use of molecular biological techniques has demonstrated the
      importance of enteroviral infection of the myocardium in the pathogenesis of
      myocarditis and dilated cardiomyopathy in adults and adenovirus and enterovirus
      infection in children. The aim of this study was to determine the frequency of
      adenoviral infection of the myocardium of adults with impaired left ventricular
      function of unknown origin. METHODS AND RESULTS: Nested polymerase chain reaction
      (nPCR) was used to determine the frequency of detection of adenoviral DNA and
      enteroviral RNA in myocardial tissue samples from 94 adult patients with
      idiopathic left ventricular dysfunction and 14 control patients. Histological and
      immunohistological analyses were performed to detect myocardial inflammation.
      Adenoviral genomic DNA was detected by nPCR in 12 of the 94 patients with left
      ventricular dysfunction (in each case, adenovirus type 2), whereas enteroviral
      RNA was detected in another 12 patients. All control samples were negative for
      both viruses. In all patients, active myocarditis was excluded according to the
      Dallas criteria. However, there was significantly decreased CD2, CD3, and CD45RO
      T lymphocyte counts in the adenovirus-positive group compared with the adenovirus
      negative group (P<0.05), whereas no differences were associated with enterovirus
      infection. CONCLUSIONS: Although enteroviruses are an important causative agent
      in the pathogenesis of myocarditis and dilated cardiomyopathy, this study shows
      that adenovirus infection is also important in the pathogenesis of left
      ventricular failure in adults. However, the pathogenetic basis of disease
      associated with adenovirus infection may be different than that after infection
      with other agents, particularly with respect to activation of the host immune
      response.

PMID- 10077521
TI  - Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in
      rabbits by secoisolariciresinol diglucoside isolated from flaxseed.
AB  - BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a plant lignan isolated
      from flaxseed. Lignans are platelet-activating factor-receptor antagonists that
      would inhibit the production of oxygen radicals by polymorphonuclear leukocytes.
      SDG is an antioxidant. Antioxidants studied thus far are known to reduce
      hypercholesterolemic atherosclerosis. The objective of this study was to
      determine the effect of SDG on various blood lipid and aortic tissue oxidative
      stress parameters and on the development of atherosclerosis in rabbits fed a high
      cholesterol diet. METHODS AND RESULTS: Rabbits were assigned to 4 groups: group
      1, control; group 2, SDG control (15 mg. kg body wt-1. d-1 PO); group 3, 1%
      cholesterol diet; and group 4, same as group 3 but with added SDG (15 mg. kg body
      wt-1. d-1 PO). Blood samples were collected before (time 0) and after 4 and 8
      weeks of experimental diets for measurement of serum triglycerides, total
      cholesterol (TC), and LDL, HDL, and VLDL cholesterol (LDL-C, HDL-C, and VLDL-C).
      The aorta was removed at the end of the protocol for assessment of
      atherosclerotic plaques; malondialdehyde, an aortic tissue lipid peroxidation
      product; and aortic tissue chemiluminescence, a marker for antioxidant reserve.
      Serum TC, LDL-C, and the ratios LDL-C/HDL-C and TC/HDL-C increased in groups 3
      and 4 compared with time 0, the increase being smaller in group 4 than in group
      3. Serum HDL-C decreased in group 3 and increased in group 4 compared with time
      0, but changes were lower in group 3 than in group 4. SDG reduced TC and LDL-C by
      33% and 35%, respectively, at week 8 but increased HDL-C significantly, by>140%,
      as early as week 4. It also decreased TC/LDL-C and LDL-C/HDL-C ratios by
      approximately 64%. There was an increase in aortic malondialdehyde and
      chemiluminescence in group 3, and they were lower in group 4 than in group 3. SDG
      reduced hypercholesterolemic atherosclerosis by 73%. CONCLUSIONS: These results
      suggest that SDG reduced hypercholesterolemic atherosclerosis and that this
      effect was associated with a decrease in serum cholesterol, LDL-C, and lipid
      peroxidation product and an increase in HDL-C and antioxidant reserve.

PMID- 10077522
TI  - Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents
      reocclusion in a porcine model.
AB  - BACKGROUND: We investigated whether administration of a soluble recombinant P
      selectin glycoprotein ligand-1 chimera (rPSGL-Ig) in conjunction with
      thrombolytic therapy would enhance thrombolysis by preventing ongoing
      interactions of leukocytes with platelets and the injured arterial wall. METHODS
      AND RESULTS: An occlusive thrombus was formed in an internal iliac artery of
      Yorkshire pigs by placement of a copper coil in the artery under fluoroscopic
      guidance. Pigs then received heparin and, 15 minutes later, either vehicle or
      rPSGL-Ig followed by infusion with 25 mg tissue plasminogen activator according
      to the 90-minute regimen. Blood flow through the artery was monitored by
      angiography and scored on a scale of 0 to 3. Lysis of the thrombus was
      accelerated by 70% in pigs treated with rPSGL-Ig 250 microg/kg compared with
      control (13.3+/-5.0 versus 44. 4+/-13.3 minutes; n=9 each). Eight of 9 control
      pigs reoccluded in 13.8+/-16.9 minutes after the end of tissue plasminogen
      activator infusion, whereas no reocclusion was observed in 8 of 9 pigs in the
      rPSGL-Ig group. When the dose of rPSGL-Ig was increased to 500 microg/kg, time to
      lysis was shortened by 61% from control (18.0+/-8. 4 versus 46.0+/-8.9 minutes).
      Reocclusion occurred in 6.0+/-15.2 minutes in control but not in any rPSGL-Ig
      treated pig (n=5 each). In addition, near-normal flow (score 2 or 3) after
      thrombolysis was achieved 59% and 58% faster in the 2 rPSGL-Ig groups than in
      their respective controls. CONCLUSIONS: Inhibition of leukocyte accumulation at
      the site of thrombosis with rPSGL-Ig may represent a safe therapeutic
      intervention that could be important in accelerating thrombolysis, achieving
      optimal reperfusion, and reducing incidence of acute reocclusion.

PMID- 10077523
TI  - Antioxidants improve impaired insulin-mediated glucose uptake and prevent
      migration and proliferation of cultured rabbit coronary smooth muscle cells
      induced by high glucose.
AB  - BACKGROUND: To explore the role of intracellular oxidative stress in high glucose
      induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol
      on the migration and growth characteristics of cultured rabbit coronary vascular
      smooth muscle cells (VSMCs). METHODS AND RESULTS: Chronic high-glucose-medium
      (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB
      mediated VSMC migration, [3H]thymidine incorporation, and cell number compared
      with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose).
      Probucol and alpha-tocopherol significantly suppressed high glucose-induced
      increase in VSMC migration, cell number, and [3H]thymidine incorporation.
      Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the
      cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase
      C activation. Probucol, alpha-tocopherol, and calphostin C improved the high
      glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic
      high-glucose treatment increased the oxidative stress, which was significantly
      suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. CONCLUSIONS:
      These findings suggest that probucol and alpha-tocopherol may suppress high
      glucose-induced VSMC migration and proliferation via suppression of increases in
      the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C
      activation induced by high glucose, which result in reduction in intracellular
      oxidative stress.

PMID- 10077524
TI  - Repeated administration of vasopressin but not epinephrine maintains coronary
      perfusion pressure after early and late administration during prolonged
      cardiopulmonary resuscitation in pigs.
AB  - BACKGROUND: It is unknown whether repeated dosages of vasopressin or epinephrine
      given early or late during basic life support cardiopulmonary resuscitation (CPR)
      may be able to increase coronary perfusion pressure above a threshold between 20
      and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS: After 4
      minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12
      animals were randomly assigned to receive, every 5 minutes, either vasopressin
      (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine
      (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12
      animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8
      minutes of basic life support CPR, to receive, every 5 minutes, either
      vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or
      epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6).
      Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM
      coronary perfusion pressure was significantly higher 90 seconds after early
      vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02;
      42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002,
      respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90
      seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/
      4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All
      vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of
      spontaneous circulation (P<0.05). CONCLUSIONS: Repeated administration of
      vasopressin but only the first epinephrine dose given early and late during basic
      life support CPR maintained coronary perfusion pressure above the threshold that
      is needed for successful defibrillation.

PMID- 10077525
TI  - Mechanism linking T-wave alternans to the genesis of cardiac fibrillation.
AB  - BACKGROUND: Although T-wave alternans has been closely associated with
      vulnerability to ventricular arrhythmias, the cellular processes underlying T
      wave alternans and their role, if any, in the mechanism of reentry remain
      unclear. METHODS AND RESULTS: -T-wave alternans on the surface ECG was elicited
      in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action
      potentials were recorded simultaneously from 128 epicardial sites with voltage
      sensitive dyes. Alternans of the repolarization phase of the action potential was
      observed above a critical threshold heart rate (HR) (209+/-46 bpm) that was
      significantly lower (by 57+/-36 bpm) than the HR threshold for alternation of
      action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR
      threshold (range, 171 to 272 bpm) of repolarization alternans varied
      substantially between cells across the epicardial surface. T-wave alternans on
      the surface ECG was explained primarily by beat-to-beat alternation in the time
      course of cellular repolarization. Above a critical HR, membrane repolarization
      alternated with the opposite phase between neighboring cells (ie, discordant
      alternans), creating large spatial gradients of repolarization. In the presence
      of discordant alternans, a small acceleration of pacing cycle length produced a
      characteristic sequence of events: (1) unidirectional block of an impulse
      propagating against steep gradients of repolarization, (2) reentrant propagation,
      and (3) the initiation of ventricular fibrillation. CONCLUSIONS: Repolarization
      alternans at the level of the single cell accounts for T-wave alternans on the
      surface ECG. Discordant alternans produces spatial gradients of repolarization of
      sufficient magnitude to cause unidirectional block and reentrant ventricular
      fibrillation. These data establish a mechanism linking T-wave alternans of the
      ECG to the pathogenesis of sudden cardiac death.

PMID- 10077526
TI  - Holt-Oram syndrome.

PMID- 10077527
TI  - The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4)
      syndrome.
AB  - Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically
      recognized by aganglionosis of the distal gastrointestinal tract. Patients
      presenting with aganglionosis in association with hypopigmentation are classified
      as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the
      disease phenotype of WS4 patients with equivalent mutations suggests the
      influence of genetic modifier loci in this disorder. Sox10(Dom)/+ mice exhibit
      variability of aganglionosis and hypopigmentation influenced by genetic
      background similar to that observed in WS4 patients. We have constructed
      Sox10(Dom)/+ congenic lines to segregate loci that modify the neural crest
      defects in these mice. Consistent with previous studies, increased lethality of
      Sox10(Dom)/+ animals resulted from a C57BL/6J locus(i). However, we also observed
      an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i).
      Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to
      mouse chromosome 10 in close proximity to a previously reported modifier of
      hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate
      further the role of SOX10 in development and disease, we have performed
      comparative genomic analyses. An essential role for this gene in neural crest
      development is supported by zoo blot hybridizations that reveal extensive
      conservation throughout vertebrate evolution and by similar Northern blot
      expression profiles between mouse and man. Comparative sequence analysis of the
      mouse and human SOX10 gene have defined the exon-intron boundaries of SOX10 and
      facilitated mutation analysis leading to the identification of two new SOX10
      mutations in individuals with WS4. Structural analysis of the HMG DNA-binding
      domain was performed to evaluate the effect of human mutations in this region.

PMID- 10077528
TI  - Identification and characterization of a homozygous deletion found in ovarian
      ascites by representational difference analysis.
AB  - We have performed representational difference analysis (RDA) on DNA from tumor
      cells and normal fibroblasts isolated from the ascites of a patient with ovarian
      cancer. Five of six products of the RDA were homozygously deleted from the tumor
      DNA. One of these products has been characterized and identifies a homozygous
      deletion of approximately 6.9 Mb at chromosome 9p21 in the original ovarian tumor
      material. This deletion encompasses CDKN2A (p16), CDKN2B (p15), and IFN-alpha.
      PCR analysis of other tumor cell lines using the novel STS based on the RDA
      product has shown it to lie between IFN-alpha and p16, and to identify the distal
      extent of a homozygous deletion in another ovarian cancer cell line. These data
      provide further evidence for a tumor suppressor locus distinct from, but mapping
      close to, p16 on 9p21. Cytogenetic analysis using comparative genomic
      hybridization (CGH) performed on the same primary tumor confirmed a loss of
      material from chromosome 9p. However, the CGH technique had neither the
      resolution nor the sensitivity to define a subregion of homozygous loss.

PMID- 10077529
TI  - The relative power of family-based and case-control designs for linkage
      disequilibrium studies of complex human diseases. II. Individual genotyping.
AB  - In this paper we consider test statistics based on individual genotyping. For
      sibships without parents, but with unaffected as well as affected sibs, we
      introduce a new test statistic (referred to as TDS), which contrasts the allele
      frequency in affected sibs versus that estimated for the parents from the entire
      sibship. For sibships without parents, this test is analogous to the TDT and is
      completely robust to nonrandom mating patterns. The efficiency of the TDS test is
      comparable to that of the THS test (which compares affected vs. unaffected sibs
      and was based on DNA pooling), for sibships with one affected child. However, as
      the number of affected sibs in the sibship grows, the relative efficiency of the
      TDS test versus the THS test also increases. For example, for sibships with three
      affected, one-third fewer families are required; for families with four affected,
      nearly half as many are required. Thus, when sibships contain multiple affected
      individuals, the TDS test provides both an increase in power and robustness to
      nonrandom mating.

PMID- 10077530
TI  - Comparative genomic analysis of the interferon/interleukin-10 receptor gene
      cluster.
AB  - Interferons and interleukin-10 are involved in key aspects of the host defence
      mechanisms. Human chromosome 21 harbors the interferon/interleukin-10 receptor
      gene cluster linked to the GART gene. This cluster includes both components of
      the interferon alpha/beta-receptor (IFNAR1 and IFNAR2) and the second components
      of the interferon gamma-receptor (IFNGR2) and of the IL-10 receptor (IL10R2). We
      report here the complete gene content of this GART-cytokine receptor gene cluster
      and the use of comparative genomic analysis to identify chicken IFNAR1, IFNAR2,
      and IL10R2. We show that the large-scale structure of this locus is conserved in
      human and chicken but not in the pufferfish Fugu rubripes. This establishes that
      the receptor components of these host defense mechanisms were fixed in an
      ancestor of the amniotes. The extraordinary diversification of the interferon
      ligand family during the evolution of birds and mammals has therefore occurred in
      the context of a fixed receptor structure.

PMID- 10077531
TI  - Analysis of 148 kb of genomic DNA around the wnt1 locus of Fugu rubripes.
AB  - The analysis of the sequence of approximately 150 kb of a genomic region
      corresponding to the wnt1 gene of the Japanese pufferfish Fugu rubripes confirms
      the compact structure of the genome. Fifteen genes were found in this region, and
      26.6% of the analyzed sequence is coding sequence. With an average intergenic
      distance of <5 kb, this gene density is comparable to that of Caenorhabditis
      elegans. The compactness of this region corresponds to the reduction of the
      overall size of the genome, consistent with the conclusion that the gene number
      in Fugu and human genomes is approximately the same. Eight of the genes have been
      mapped in the human genome and all of them are found in the chromosomal band
      12q13, indicating a high degree of synteny in both species, Fugu and human.
      Comparative sequence analysis allows us to identify potential regulatory elements
      for wnt1 and ARF3, which are common to fish and mammals.

PMID- 10077532
TI  - Postsynaptic alpha-neurotoxin gene of the spitting cobra, Naja naja sputatrix:
      structure, organization, and phylogenetic analysis.
AB  - The venom of the spitting cobra, Naja naja sputatrix contains highly potent alpha
      neurotoxins (NTXs) in addition to phospholipase A2 (PLA2) and cardiotoxin (CTX).
      In this study, we report the complete characterization of three genes that are
      responsible for the synthesis of three isoforms of alpha-NTX in the venom of a
      single spitting cobra. DNA amplification by long-distance polymerase chain
      reaction (LD-PCR) and genome walking have provided information on the gene
      structure including their promoter and 5' and 3' UTRs. Each NTX isoform is
      approximately 4 kb in size and contains three exons and two introns. The sequence
      homology among these isoforms was found to be 99%. Two possible transcription
      sites were identified by primer extension analysis and they corresponded to the
      adenine (A) nucleotide at positions +1 and -45. The promoter also contains two
      TATA boxes and a CCAAT box. Putative binding sites for transcriptional factors AP
      2 and GATA are also present. The high percentage of similarity observed among the
      NTX gene isoforms of N. n. sputatrix as well as with the alpha-NTX and kappa-NTX
      genes from other land snakes suggests that the NTX gene has probably evolved from
      a common ancestral gene.

PMID- 10077534
TI  - DNA sequence chromatogram browsing using JAVA and CORBA.
AB  - DNA sequence chromatograms (traces) are the primary data source for all large
      scale genomic and expressed sequence tags (ESTs) sequencing projects. Access to
      the sequencing trace assists many later analyses, for example contig assembly and
      polymorphism detection, but obtaining and using traces is problematic. Traces are
      not collected and published centrally, they are much larger than the base calls
      derived from them, and viewing them requires the interactivity of a local
      graphical client with local data. To provide efficient global access to DNA
      traces, we developed a client/server system based on flexible Java components
      integrated into other applications including an applet for use in a WWW browser
      and a stand-alone trace viewer. Client/server interaction is facilitated by CORBA
      middleware which provides a well-defined interface, a naming service, and
      location independence. [The software is packaged as a Jar file available from the
      following URL: http://www.ebi.ac.uk/jparsons. Links to working examples of the
      trace viewers can be found at http://corba.ebi.ac.uk/EST. All the Washington
      University mouse EST traces are available for browsing at the same URL.]

PMID- 10077533
TI  - High-resolution physical and genetic mapping of the critical region for Meckel
      syndrome and Mulibrey Nanism on chromosome 17q22-q23.
AB  - Previously, we assigned the genes for two autosomal recessive disorders, Meckel
      syndrome (MKS; MIM 249000) and Mulibrey Nanism [MUL (muscle-liver-brain-eye
      Nanism); MIM 253250] that are enriched in the Finnish population, to overlapping
      genomic regions on chromosome 17q. Now, we report the construction of a bacterial
      clone contig over the critical region for both disorders. Several novel CA-repeat
      markers were isolated from these clones, which allowed refined mapping of the MKS
      and MUL loci using haplotype and linkage disequilibrium analysis. The
      localization of the MKS locus was narrowed to <1 cM between markers D17S1290 and
      132-CA, within an approximately 800-kb region. The MUL locus was refined into an
      approximately 1400-kb interval between markers D17S1290 and 52-CA. The whole MKS
      region falls within the MUL region. In the common critical region, the conserved
      haplotypes were different in MKS and MUL patients. A trancript map was
      constructed by assigning expressed sequence tags (ESTs) and genes, derived from
      the human gene map, to the bacterial clone contig. Altogether, four genes and a
      total of 20 ESTs were precisely localized. These data provide the molecular tools
      for the final identification of the MKS and the MUL genes.

PMID- 10077535
TI  - Detecting selective expression of genes and proteins.
AB  - Selective expression of a gene product (mRNA or protein) is a pattern in which
      the expression is markedly high, or markedly low, in one particular tissue
      compared with its level in other tissues or sources. We present a computational
      method for the identification of such patterns. The method combines assessments
      of the reliability of expression quantitation with a statistical test of
      expression distribution patterns. The method is applicable to small studies or to
      data mining of abundance data from expression databases, whether mRNA or protein.
      Though the method was developed originally for gene-expression analyses, the
      computational method is, in fact, rather general. It is well suited for the
      identification of exceptional values in many sorts of intensity data, even noisy
      data, for which assessments of confidences in the sources of the intensities are
      available. Moreover, the method is indifferent as to whether the intensities are
      experimentally or computationally derived. We show details of the general method
      and examples of computational results on gene abundance data.

PMID- 10077536
TI  - Analysis of sequence-tagged-connector strategies for DNA sequencing.
AB  - The BAC-end sequencing, or sequence-tagged-connector (STC), approach to genome
      sequencing involves sequencing the ends of BAC inserts to scatter sequence tags
      (STCs) randomly across the genome. Once any BAC or other large segment of DNA is
      sequenced to completion by conventional shotgun approaches, these STC tags can be
      used to identify a minimum tiling path of BAC clones overlapping the nucleation
      sequence for sequence extension. Here, we explore the properties of STC
      sequencing strategies within a mathematical model of a random target with
      homologous repeats and imperfect sequencing technology to understand the
      consequences of varying various parameters on the incidence of problem clones and
      the cost of the sequencing project. Problem clones are defined as clones for
      which either (A) there is no identifiable overlapping STC to extend the sequence
      in a particular direction or (B) the identified STC with minimum overlap comes
      from a nonoverlapping clone, either owing to random false matches or repeat
      family homology. Based on the minimum overlap, we estimate the number of clones
      to be entirely sequenced and, then, using cost estimates, identify the decision
      rule (the degree of sequence similarity required before a match is declared
      between an STC and a clone) to minimize overall sequencing cost. A method to
      optimize the overlap decision rule is highly desirable, because both the total
      cost and the number of problem clones are shown to be highly sensitive to this
      choice. For a target of 3 Gb containing approximately 800 Mb of repeats with 85%
      90% identity, we expect <10 problem clones with 15 times coverage by 150-kb
      clones. We derive the optimal redundancy and insert sizes of clone libraries for
      sequencing genomes of various sizes, from microbial to human. We estimate that
      establishing the resource of STCs as a means of identifying minimally overlapping
      clones represents only 1%-3% of the total cost of sequencing the human genome,
      and, up to a point of diminishing returns, a larger STC resource is associated
      with a smaller total sequencing cost.

PMID- 10077537
TI  - An efficient DNA sequencing strategy based on the bacteriophage mu in vitro DNA
      transposition reaction.
AB  - A highly efficient DNA sequencing strategy was developed on the basis of the
      bacteriophage Mu in vitro DNA transposition reaction. In the reaction, an
      artificial transposon with a chloramphenicol acetyltransferase (cat) gene as a
      selectable marker integrated into the target plasmid DNA containing a 10.3-kb
      mouse genomic insert to be sequenced. Bacterial clones carrying plasmids with the
      transposon insertions in different positions were produced by transforming
      transposition reaction products into Escherichia coli cells that were then
      selected on appropriate selection plates. Plasmids from individual clones were
      isolated and used as templates for DNA sequencing, each with two primers specific
      for the transposon sequence but reading the sequence into opposite directions,
      thus creating a minicontig. By combining the information from overlapping
      minicontigs, the sequence of the entire 10,288-bp region of mouse genome
      including six exons of mouse Kcc2 gene was obtained. The results indicated that
      the described methodology is extremely well suited for DNA sequencing projects in
      which considerable sequence information is on demand. In addition, massive DNA
      sequencing projects, including those of full genomes, are expected to benefit
      substantially from the Mu strategy.

PMID- 10077538
TI  - Integrins and human intestinal cell functions.
AB  - Integrins are a large family of cell-surface receptors involved in cell adhesion
      to the extracellular matrix. In epithelia, it is mainly the integrins belonging
      to the beta1 and beta4 classes that bind to basement membrane molecules such as
      the laminins and the type IV collagens. Beta1 and beta4 integrins regulate the
      assembly of adhesive junctions as well as the activation of various signaling
      pathways leading to the modulation of gene expression. In this review, I will
      discuss what is currently known about integrins in human intestinal epithelial
      cells. The interest in the intestinal cell model to analyze cell-matrix
      interactions will be delineated and the recent experimental evidence showing that
      these interactions can regulate cell proliferation and differentiation will be
      presented.

PMID- 10077539
TI  - Aging and cancer of the stomach and colon.
AB  - Although the incidence of most human malignancies including cancer of the
      gastrointestinal tract increases dramatically with advancing age, the precise
      role of aging in that increase remains a matter of continued controversy. Many
      probable explanations for the age-related rise in cancer incidence have been
      offered including altered carcinogen metabolism and the cumulative effects of
      protracted exposure to cancer-causing agents. Neoplasia of the stomach or colon
      is a multi-stage process with hyperproliferation being central to the initiation
      of carcinogenesis. Since aging is associated with increased gastrointestinal
      mucosal cell proliferation, the possibility that aging itself may render target
      cells more susceptible to carcinogenic transformation continues to be an area of
      intense interest and study. This review will examine the evidence for age-related
      alterations in the structural and functional properties of the gastric and
      colonic mucosa in an effort to further elucidate the potential mechanisms of
      carcinogenesis which may be involved during the aging process.

PMID- 10077540
TI  - Gastrointestinal mucosal regeneration: role of growth factors.
AB  - Growth factors and their receptors play important roles in cell proliferation,
      migration, tissue injury repair and ulcer healing. In gastric mucosa,
      transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) by
      activating their common receptor, control cell proliferation. TGF-alpha
      predominantly plays this role under normal conditions and after acute injury,
      while EGF exerts its actions mainly during healing of chronic ulcers. During
      regeneration of injured gastric mucosa, these growth factors serve predominantly
      to restore the epithelial component. Other growth factors, basic fibroblast
      growth factor (bFGF) and vascular endothelial growth factor (VEGF) serve to
      promote restoration of the connective tissue and microvessels (angiogenesis) in
      injured mucosa. During healing of chronic ulcers, a new epithelial lineage
      secreting EGF and other growth peptides develops and the majority of cells lining
      the ulcer margin overexpress the EGF receptor. Activation of the EGF receptor
      induces dramatic increases in MAP (Erk -1 and -2) kinase activity and
      phosphorylation levels. Inhibition of this signaling pathway dramatically delays
      ulcer healing. Granulation connective tissue, which grows under the stimulation
      of bFGF and VEGF is the major source for regeneration of connective tissue lamina
      propria and microvessels within the ulcer scar. Other growth factors such as
      insulin - like growth factor, keratinocyte growth factor, hepatocyte growth
      factor and trefoil peptides have been implicated in gastrointestinal (gastric
      ulcers, colitis) regeneration following injury. This paper is intended to provide
      an overview of the role of growth factors in gastrointestinal mucosal
      regeneration.

PMID- 10077541
TI  - Lineage commitment and maturation of epithelial cells in the gut.
AB  - The dynamic concepts of gut epithelial cell populations which heralded the era of
      modern gut cell biology have been generally substantiated by recent studies and
      are still being correlated with functional properties. Multipotent stem cells are
      anchored in specific locations along the gut epithelium where decisions
      concerning proliferation and differentiation/migration pathways are made. Stem
      cells give rise to lineage precursors which transform into transit cells and
      sequentially express lineage specific features during their differentiation
      program. Morphologically and functionally mature cells along the gut epithelium
      are dynamically heterogeneous. 1) The squamous lineage of the esophagus forms a
      stratified epithelium which has an average turnover time of about 7. 5 days. 2)
      In the stomach, the oxyntic pit-gland unit includes pit, zymogenic and parietal
      cells which respectively migrate outwards, inwards, and in both directions; their
      turnover times average 3, 194 and 54 days, respectively. 3) The mucous units of
      the pyloric antrum are populated by pit cells which migrate outwards and gland
      cells which migrate inwards; their turnover times are about 3 and 1-60 days,
      respectively. 4) In the crypt-villus units of the small intestine, while both
      absorptive and goblet cells migrate outwards and for each the turnover time is
      about 3 days, Paneth cells migrate inwards and their turnover time is about 15
      days. 5) In the crypts of the descending colon, both vacuolated-columnar and
      goblet cells migrate outwards and for each the turnover time is about 5 days. The
      ascending colon has an additional cell type called deep crypt secretory cells
      which migrate inwards and their turnover time is about 14-21 days. Finally, while
      the factors maintaining the gut epithelium in a steady state remain to be
      elucidated, this epithelium represents a remarkable system for studying the
      biological features of stem cells and their hierarchies.

PMID- 10077542
TI  - Life among the primitives: protein O-phosphatases in prokaryotes.
AB  - Prokaryotes contain at least five distinct families of protein O-phosphatases,
      including AceK, the chimeric isocitrate dehydrogenase kinase/phosphatase, and
      four protein phosphatase families first identified and characterized in
      Eukaryotes. The latter consist of the PPP and PPM families of protein
      serine/threonine phosphatases, and the low molecular weight and conventional
      families of protein-tyrosine phosphatases. Prokaryotic protein O-phosphatases
      participate in the regulation of metabolic processes and the transduction of
      environmental signals. Certain pathogenic bacteria employ protein-tyrosine
      phosphatases as virulence factors, injecting them into host cells where they
      enzymatically perturb the phosphorylation state of proteins therein. While our
      understanding of protein O-phosphorylation events in Prokaryotes only now is
      emerging from its infancy, their phylogenetic diversity and malleability to
      genetic manipulation render these "simple'" organisms powerful vehicles for
      answering fundamental questions concerning the origins and evolution of this key
      biological regulatory mechanism.

PMID- 10077543
TI  - Phosphorylase phosphatase: new horizons for an old enzyme.
AB  - Protein phosphatase-1, originally studied as phosphorylase phosphatase, is one of
      the major ser/thr protein phosphatases. It has a long history and a complex
      enzymology. It consists of a catalytic subunit of 37 kDa, which is bound to a
      number of different regulatory or targeting subunits. These are believed to
      restrict its activity to its immediate microenvironment and thus define its
      specificity, as well as acting to regulate phosphatase activity. The existence of
      multiple protein phosphatase-1 binding proteins provides the mechanism whereby
      phosphatase-1 activity can be involved in a diverse range of cellular functions,
      and reflects a novel strategy for its evolutionary development.

PMID- 10077544
TI  - Antioxidant enzymes and their implications in pathophysiologic processes.
AB  - Aerobic organisms possess antioxidant defense systems that deal with reactive
      oxygen species (ROS) produced as a consequence of aerobic respiration. Reactive
      oxygen is related to both, the arrest of growth and the start of cell
      differentiation. Low concentrations of reactive oxygen intermediates may be
      beneficial or even indispensable in processes such as intracellular messaging and
      defense against micro-organisms, but higher amounts of active oxygen may be
      harmful to cells and organisms. A wide array of non-enzymatic and enzymatic
      antioxidant defenses exists, including superoxide dismutase (SOD), glutathione
      peroxidase (GPX) and catalase (CAT). We describe their main characteristics and
      how these antioxidant enzymes work together against active oxygen. Small
      deviations from their physiological values may have a dramatic effect on the
      resistance of cells to oxidative damage to lipids, proteins and DNA.
      Consequently, toxic oxygen play a role in aging process as well as in a number of
      human diseases that we list in this review.

PMID- 10077545
TI  - Epstein-Barr virus immortalization and latency.
AB  - Epstein-Barr virus infects human B lymphocytes. The interaction between the virus
      and these cells has been the subject of investigation for over three decades.
      Recent in vitro and in vivo studies, reviewed here, are revealing the mechanisms
      by which EBV induces and controls proliferation through the expression of six
      viral nuclear proteins and two plasma membrane proteins. This genetic program is
      referred to as immortalization and it is suggested that the purpose of
      immortalization is to use the innate proliferative potential of B cells to
      inflate the numbers of infected cells prior to virus production and cell lysis.
      Latency, on the other hand, has only been detected in situ in latently infected
      humans. It is characterized by the presence of very low numbers of viral episomes
      that appear to express the RNA for only one protein (Latent Membrane Protein 2)
      in B cells that bear the markers of a non-activated resting memory subset. Two
      models are proposed for the mechanism that establishes this state. The
      differences between immortalization and latency are highlighted in this review
      and it is suggested that many of the functions currently attributed to latency
      are actually features of immortalization. An appreciation of this distinction may
      assist the discussion of the nature of the interaction between the virus and the
      host in EBV-associated lymphoproliferative diseases and tumors.

PMID- 10077546
TI  - Polyps as biomarkers for colorectal neoplasia.
AB  - Current understanding of colorectal carcinogenesis suggests a series of genetic
      changes occurring pari passu with morphological changes ultimately resulting in a
      cancerous lesion. The adenomatous polyp was originally the prototype of the
      preneoplastic lesion but recently, other colonic polyps, primarily the
      hamartomas, have been clinically characterized as colorectal cancer biomarkers
      with genetic changes found mainly in the mesenchymal component as opposed to the
      ectodermal, or epithelial element. This, with the current interest in
      angiogenesis playing a role in the propagation of neoplastic lesions, has now
      encompassed every tissue element and opened the way for an understanding of the
      oncogenic process. This has suggested that considerable interaction occurs
      between all tissue elements, including what was previously described as
      epithelial-matrix interactions. While hyperplastic polyps are thought not to
      confer risk for cancer, they may offer clues as to the first steps of the overall
      process. Microadenomas have introduced new clinical as well as biological
      considerations, as unique risk factors. Investigation of these lesions has moved
      from purely morphological correlations to mechanistic dissections of important
      biological pathways using both genetic and protein chemistry tools. This review
      explores the microcosm of the colonic polyp and its relation to cancer as the
      quintessential premalignant biomarker.

PMID- 10077547
TI  - Fit for life in the immune system? Surrogate L chain tests H chains that test L
      chains.

PMID- 10077548
TI  - A notable cleavage: winding up with beta-amyloid.

PMID- 10077549
TI  - Heart or hand? Unmasking the basis for specific Holt-Oram phenotypes.

PMID- 10077550
TI  - More surprises from Kinetoplastida.

PMID- 10077551
TI  - More on the X files.

PMID- 10077552
TI  - Attention and primary visual cortex.

PMID- 10077553
TI  - The dynamic dialogue between cells and matrices: implications of fibronectin's
      elasticity.

PMID- 10077554
TI  - A hierarchical approach to protein molecular evolution.
AB  - Biological diversity has evolved despite the essentially infinite complexity of
      protein sequence space. We present a hierarchical approach to the efficient
      searching of this space and quantify the evolutionary potential of our approach
      with Monte Carlo simulations. These simulations demonstrate that nonhomologous
      juxtaposition of encoded structure is the rate-limiting step in the production of
      new tertiary protein folds. Nonhomologous "swapping" of low-energy secondary
      structures increased the binding constant of a simulated protein by approximately
      10(7) relative to base substitution alone. Applications of our approach include
      the generation of new protein folds and modeling the molecular evolution of
      disease.

PMID- 10077556
TI  - Femtosecond dynamics of dative bonding: concepts of reversible and dissociative
      electron transfer reactions.
AB  - With fs time, speed, and angular resolution of the elementary steps in electron
      transfer reactions, we report direct observation of reversible and dissociative
      processes for dative bonding involving covalent and ionic characters. For
      bimolecular reactions of various donors and acceptors we find strong correlation
      between the structure and the dynamics. The dynamics from the transition state to
      final products involve two elementary processes, with different reaction times,
      speed, and angular distributions. For example, for the R2S.I2 (R = C2H5) system,
      it is shown that after charge separation, the reversible electron transfer occurs
      in less than 150 fs (fastest trajectory) and is followed by the rupture of the I
      I bond with the release of the first I-atom in 510 fs. However, the second
      process of the remaining and trapped I-atom takes 1.15 ps with its speed (500
      m/s) being much smaller than the first one (1,030 m/s). The S-I-I average angle
      is 130 degrees. These findings, on this and the other systems reported here,
      elucidate the mechanism and address some concepts of nonconcertedness, caging,
      and restricted energy redistribution.

PMID- 10077555
TI  - The topomer-sampling model of protein folding.
AB  - Clearly, a protein cannot sample all of its conformations (e.g., approximately
      3(100) approximately 10(48) for a 100 residue protein) on an in vivo folding
      timescale (<1 s). To investigate how the conformational dynamics of a protein can
      accommodate subsecond folding time scales, we introduce the concept of the native
      topomer, which is the set of all structures similar to the native structure
      (obtainable from the native structure through local backbone coordinate
      transformations that do not disrupt the covalent bonding of the peptide
      backbone). We have developed a computational procedure for estimating the number
      of distinct topomers required to span all conformations (compact and semicompact)
      for a polypeptide of a given length. For 100 residues, we find approximately 3 x
      10(7) distinct topomers. Based on the distance calculated between different
      topomers, we estimate that a 100-residue polypeptide diffusively samples one
      topomer every approximately 3 ns. Hence, a 100-residue protein can find its
      native topomer by random sampling in just approximately 100 ms. These results
      suggest that subsecond folding of modest-sized, single-domain proteins can be
      accomplished by a two-stage process of (i) topomer diffusion: random, diffusive
      sampling of the 3 x 10(7) distinct topomers to find the native topomer (
      approximately 0.1 s), followed by (ii) intratopomer ordering: nonrandom, local
      conformational rearrangements within the native topomer to settle into the
      precise native state.

PMID- 10077557
TI  - Protein folding at the air-water interface studied with x-ray reflectivity.
AB  - We report the results of x-ray reflectivity measurements of thin films formed by
      different water-soluble proteins at the air-aqueous solution interface. It is
      demonstrated that glucose oxidase, alcohol dehydrogenase, and urease molecules
      denaturate at the air-aqueous solution interface to form 8- to 14-A-thick peptide
      sheets. X-ray reflectivity data indicate that the spreading of a lipid monolayer
      at the aqueous solution surface before protein injection does not prevent
      proteins from unfolding. On the other hand, crosslinking of proteins results in
      intact enzyme layers at the subphase surface. A model that involves interaction
      of glucose oxidase molecules with a phospholipid monolayer is proposed. In this
      model, an observed decrease of the lipid electron density in the protein presence
      is explained in terms of "holes" in the monolayer film caused by protein molecule
      adsorption.

PMID- 10077558
TI  - On the behavior of hyperbolic neutral points in two-dimensional ideal
      magnetohydrodynamics.
AB  - We study ideal incompressible magnetohydrodynamics in two dimensions. We obtain
      an exponential estimate on the closing of the angle at hyperbolic saddle points
      of the magnetic stream function under the assumption that the velocity remains
      bounded. The analytic results are supported by numerical simulations. These
      results give evidence against a standard scenario for singularity formation for
      these equations.

PMID- 10077559
TI  - Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus
      vector.
AB  - Adenovirus (Ad) and adeno-associated virus (AAV) have attractive and
      complementary properties that can be exploited for gene transfer purposes. Ad
      vectors are probably the most efficient vehicles to deliver foreign genes both in
      vitro and in vivo. AAV exhibits the unique ability to establish latency by
      efficiently integrating at a specific locus of human chromosome 19 (AAVS1). Two
      viral elements are necessary for the integration at AAVS1: Rep68/78 and the
      inverted terminal repeats (AAV-ITRs). In this study, we report the development of
      two helper-dependent adenoviral (HD) vectors, one carrying the Rep78 gene, the
      other an AAV-ITR-flanked transgene. Although Rep proteins have been demonstrated
      to interfere with Ad replication, HD Rep78 vector was successfully amplified on
      serial passages in 293CRE4 cells with a yield of 50-100 transducing units per
      cell. DNA integration at the AAVS1 site also was demonstrated in hepatoma cells
      coinfected with the HD-expressing Rep78 and with the second HD vector carrying a
      transgene flanked by AAV-ITRs. The high transduction efficiency, large cloning
      capacity, and high titer of the HD, combined with the site-specific integration
      machinery provided by AAV-derived components, make the Ad/AAV hybrid viruses a
      promising vehicle for gene therapy.

PMID- 10077560
TI  - Structural characteristics of supramolecular assemblies formed by guanidinium
      cholesterol reagents for gene transfection.
AB  - We have recently discovered that cationic cholesterol derivatives characterized
      by guanidinium polar headgroups are very efficient for gene transfection in vitro
      and in vivo. In spite of being based on some rationale at the molecular level,
      the development of these new synthetic vectors was nevertheless empirical.
      Indeed, the factors and processes underlying cationic lipid-mediated gene
      transfer are still poorly understood. Thus, to get a better insight into the
      mechanisms involved, we have examined the supramolecular structure of lipid/DNA
      aggregates obtained when using reagent bis(guanidinium)-tren-cholesterol (BGTC),
      either alone or as a liposomal formulation with the neutral phospholipid dioleoyl
      phosphatidylethanolamine (DOPE). We here report the results of cryotransmission
      electron microscopy studies and small-angle x-ray scattering experiments,
      indicating the presence of multilamellar domains with a regular spacing of 70 A
      and 68 A in BGTC/DOPE-DNA and BGTC-DNA aggregates, respectively. In addition, DNA
      lipoplexes with similar lamellar patterns were detected inside transfected HeLa
      cells by conventional transmission electron microscopy. These results suggest
      that DNA condensation by multivalent guanidinium-cholesterol cationic lipids
      involves the formation of highly ordered multilamellar domains, the DNA molecules
      being intercalated between the lipid bilayers. These results also invite further
      investigation of the intracellular fate of the internalized lipid/DNA structures
      during their trafficking toward the cell nucleus. The identification of the basic
      features of active complexes should indeed help in the design of improved
      guanidinium-based vectors.

PMID- 10077561
TI  - Modulation of CREB binding protein function by the promyelocytic (PML)
      oncoprotein suggests a role for nuclear bodies in hormone signaling.
AB  - Disaggregation of the spherical nuclear bodies termed promyelocytic (PML)
      oncogenic domains (PODs) is a characteristic of acute promyelocytic leukemia.
      Here, we demonstrate that the cAMP enhancer binding protein (CREB)-binding
      protein (CBP) associates with PML in vitro and is recruited to the PODs in vivo.
      Through its association with CBP, wild-type PML dramatically stimulates nuclear
      receptor transcriptional activity. These results demonstrate that a fraction of
      CBP is compartmentalized to the POD through its association with PML and thus
      suggest that PML and other POD-associated proteins may play an unexpectedly broad
      role in aspects of transcriptional regulation and human disease.

PMID- 10077562
TI  - Human T-cell leukemia retrovirus-Tax protein is a repressor of nuclear receptor
      signaling.
AB  - The Tax oncoprotein promotes cellular transformation and is associated with the
      pathogenesis of adult T-cell leukemia. Tax expression activates transcription via
      the cAMP enhancer binding protein/activating transcription factor (CREB/ATF) and
      NF-kappaB pathways. In contrast to its positive action, here we demonstrate that
      Tax is a potent repressor of steroid and retinoid receptor transcription. The Tax
      protein becomes localized in the promyelocytic (PML) oncogenic domain, and
      unexpectedly, expression of the PML protein reverses Tax-induced repression.
      These results suggest that PML and Tax may act in opposing manners to influence
      nuclear receptor transcription and human T-cell leukemia retrovirus pathogenesis.

PMID- 10077563
TI  - Unique forms of human and mouse nuclear receptor corepressor SMRT.
AB  - Nuclear hormone receptors have been shown to repress transcription in the absence
      of ligand. This repression is mediated by a corepressor complex that contains the
      Sin3A protein and histone deacetylases (HDAC1 and 2). Studies by several groups
      demonstrate that this complex is recruited to nuclear receptors through the
      highly related corepressors SMRT (silencing mediator of retinoid acid and thyroid
      hormone receptor) and N-CoR (nuclear receptor corepressor). We describe here the
      cloning, characterization, and chromosomal mapping of forms of human and mouse
      SMRT that includes a 1,000-aa extension, which reveals striking homology to the
      amino terminus of N-CoR. Structure and function studies of wild-type and natural
      splicing variants suggest the presence of 3-4 amino terminal domains that repress
      in a cooperative as well as mechanistically distinct fashion.

PMID- 10077564
TI  - Troponin I is present in human cartilage and inhibits angiogenesis.
AB  - Cartilage is an avascular and relatively tumor-resistant tissue. Work from a
      number of laboratories, including our own, has demonstrated that cartilage is an
      enriched source of endogenous inhibitors of angiogenesis. In the course of a
      study designed to identify novel cartilage-derived inhibitors of new capillary
      growth, we have purified an inhibitory protein that was identified by peptide
      microsequencing and protein database analysis as troponin I (TnI). TnI is a
      subunit of the troponin complex (troponin-C and troponin-T being the other two),
      which, along with tropomyosin, is responsible for the calcium-dependent
      regulation of striated muscle contraction; independently, TnI is capable of
      inhibiting actomyosin ATPase. Because troponin has never previously been reported
      to be present in cartilage, we have cloned and expressed the cDNA of human
      cartilage TnI, purified this protein to apparent homogeneity, and demonstrated
      that it is a potent and specific inhibitor of angiogenesis in vivo and in vitro,
      as well as of tumor metastasis in vivo.

PMID- 10077565
TI  - Serine-arginine (SR)-rich splicing factors have an exon-independent function in
      pre-mRNA splicing.
AB  - Two distinct functions have been proposed for the serine-arginine (SR)-rich
      family of splicing factors. First, SR proteins are essential splicing factors and
      are thought to function by mediating protein-protein interactions within the
      intron during spliceosome assembly. Second, SR proteins bind to exonic enhancer
      sequences and recruit spliceosome components to adjacent introns. The latter
      activity is required for splice-site recognition and alternative splicing. Until
      now it has not been possible to determine whether the requirement for SR proteins
      in the basic splicing reaction is a secondary consequence of their exon-dependent
      recruitment function. Here we show that RNA substrates containing only 1 nt of
      exon sequence can undergo the first step of the splicing reaction in vitro and
      that this activity requires SR proteins. Thus, we provide direct evidence that SR
      proteins have both exon-independent and exon-dependent functions in pre-mRNA
      splicing.

PMID- 10077566
TI  - The fission yeast homologue of Orc4p binds to replication origin DNA via multiple
      AT-hooks.
AB  - The origin recognition complex (ORC) was originally identified in the yeast
      Saccharomyces cerevisiae as a protein that specifically binds to origins of DNA
      replication. Although ORC appears to play an essential role in the initiation of
      DNA replication in the cells of all eukaryotes, its interactions with DNA have
      not been defined in species other than budding yeast. We have characterized a
      Schizosaccharomyces pombe homologue of the ORC subunit, Orc4p. The homologue
      (Orp4p) consists of two distinct functional domains. The C-terminal domain shows
      strong sequence similarity to human, frog, and yeast Orc4 proteins, including
      conserved ATP-binding motifs. The N-terminal domain contains nine copies of the
      AT-hook motif found in a number of DNA-binding proteins, including the members of
      the HMG-I(Y) family of chromatin proteins. AT-hook motifs are known from
      biochemical and structural studies to mediate binding to the minor groove of AT
      tracts in DNA. Orp4p is essential for viability of Sc. pombe and is expressed
      throughout the cell cycle. The Orp4 protein (and its isolated N-terminal domain)
      binds to the Sc. pombe replication origin, ars1. The DNA binding properties of
      Orp4p provide a plausible explanation for the characteristic features of Sc.
      pombe origins of replication, which differ significantly from those of Sa.
      cerevisiae.

PMID- 10077567
TI  - Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A
      resolution.
AB  - Ebola virions contain a surface transmembrane glycoprotein (GP) that is
      responsible for binding to target cells and subsequent fusion of the viral and
      host-cell membranes. GP is expressed as a single-chain precursor that is
      posttranslationally processed into the disulfide-linked fragments GP1 and GP2.
      The GP2 subunit is thought to mediate membrane fusion. A soluble fragment of the
      GP2 ectodomain, lacking the fusion-peptide region and the transmembrane helix,
      folds into a stable, highly helical structure in aqueous solution. Limited
      proteolysis studies identify a stable core of the GP2 ectodomain. This 74-residue
      core, denoted Ebo-74, was crystallized, and its x-ray structure was determined at
      1.9-A resolution. Ebo-74 forms a trimer in which a long, central three-stranded
      coiled coil is surrounded by shorter C-terminal helices that are packed in an
      antiparallel orientation into hydrophobic grooves on the surface of the coiled
      coil. Our results confirm the previously anticipated structural similarity
      between the Ebola GP2 ectodomain and the core of the transmembrane subunit from
      oncogenic retroviruses. The Ebo-74 structure likely represents the fusion-active
      conformation of the protein, and its overall architecture resembles several other
      viral membrane-fusion proteins, including those from HIV and influenza.

PMID- 10077568
TI  - Transcriptional activation by artificial recruitment in yeast is influenced by
      promoter architecture and downstream sequences.
AB  - The idea that recruitment of the transcriptional machinery to a promoter suffices
      for gene activation is based partly on the results of "artificial recruitment"
      experiments performed in vivo. Artificial recruitment can be effected by a
      "nonclassical" activator comprising a DNA-binding domain fused to a component of
      the transcriptional machinery. Here we show that activation by artificial
      recruitment in yeast can be sensitive to any of three factors: position of the
      activator-binding elements, sequence of the promoter, and coding sequences
      downstream of the promoter. In contrast, classical activators worked efficiently
      at all promoters tested. In all cases the "artificial recruitment" fusions
      synergized well with classical activators. A classical activator evidently
      differs from a nonclassical activator in that the former can touch multiple sites
      on the transcriptional machinery, and we propose that that difference accounts
      for the broader spectrum of activity of the typical classical activator. A
      similar conclusion is reached from studies in mammalian cells in the accompanying
      paper [Nevado, J., Gaudreau, L., Adam, M. & Ptashne, M. (1999) Proc. Natl. Acad.
      Sci. USA 96, 2674-2677].

PMID- 10077569
TI  - Transcriptional activation by artificial recruitment in mammalian cells.
AB  - We show that the typical "nonclassical" activator, which comprises a fusion
      protein bearing a component of the transcriptional machinery fused to a DNA
      binding domain, activates transcription in mammalian cells only weakly when
      tested with an array of promoters. However, as found in analogous "artificial
      recruitment" experiments performed in yeast, these activators work
      synergistically with "classical" activators. The effect of the classical
      activator in such experiments requires that it be tethered to DNA, a requirement
      that cannot be overcome by expression of that classical activator at high levels.
      The effect of the one nonclassical activator that does elicit significant levels
      of transcription when working alone (i.e., that bearing TATA box-binding protein)
      is strongly influenced by promoter architecture. The results, consistent with
      those of analogous experiments in yeast [see the accompanying paper: Gaudreau,
      L., Keaveney, M., Nevado, J., Zaman, Z., Bryant, G. O., Struhl, K. & Ptashne, M.
      (1999) Proc. Natl. Acad. Sci. USA 96, 2668-2673], suggest that classical
      activators, presumably by virtue of their abilities to interact with multiple
      targets, have a functional flexibility that nonclassical activators lack.

PMID- 10077570
TI  - Lysozyme and RNases as anti-HIV components in beta-core preparations of human
      chorionic gonadotropin.
AB  - Human chorionic gonadotropin (hCG) preparations contain activity against HIV type
      1 (HIV-1). However, there has been controversy about whether some biological
      activities of hCG beta-subunit (hCGbeta) preparations are caused by the beta
      subunit itself or other proteins present in the preparations. We report here the
      purification, characterization, and identification of three enzymes with anti-HIV
      activity present in the beta-core fraction of hCGbeta prepared from the urine of
      pregnant women. The N-terminal amino acid sequence of one protein is identical to
      human urinary lysozyme C, and those of the other two are identical to human RNase
      A and urinary RNase U. We thus refer to these proteins as AVL (antiviral
      lysozyme) and AVR (antiviral RNases). In addition to HIV-1 inhibition, AVL is
      capable of lysing Micrococcus lysodeikticus. AVR digests a variety of RNA
      substrates, including RNA from HIV-1-infected cells. We also find that lysozyme
      from chicken egg white, human milk, and human neutrophils and RNase A from bovine
      pancreas possess activity against HIV-1. These findings may offer additional
      strategies for the treatment of HIV-1 infection.

PMID- 10077571
TI  - GroES in the asymmetric GroEL14-GroES7 complex exchanges via an associative
      mechanism.
AB  - The interaction of the chaperonin GroEL14 with its cochaperonin GroES7 is
      dynamic, involving stable, asymmetric 1:1 complexes (GroES7.GroEL7-GroEL7) and
      transient, metastable symmetric 2:1 complexes [GroES7.GroEL7-GroEL7.GroES7]. The
      transient formation of a 2:1 complex permits exchange of free GroES7 for GroES7
      bound in the stable 1:1 complex. Electrophoresis in the presence of ADP was used
      to resolve free GroEL14 from the GroES7-GroEL14 complex. Titration of GroEL14
      with radiolabeled GroES7 to molar ratios of 32:1 demonstrated a 1:1 limiting
      stoichiometry in a stable complex. No stable 2:1 complex was detected.
      Preincubation of the asymmetric GroES7.GroEL7-GroEL7 complex with excess
      unlabeled GroES7 in the presence of ADP demonstrated GroES7 exchange. The rates
      of GroES7 exchange were proportional to the concentration of unlabeled free
      GroES7. This concentration dependence points to an associative mechanism in which
      exchange of GroES7 occurs by way of a transient 2:1 complex and excludes a
      dissociative mechanism in which exchange occurs by way of free GroEL14. Exchange
      of radiolabeled ADP from 1:1 complexes was much slower than the exchange of
      GroES7. In agreement with recent structural studies, this indicates that
      conformational changes in GroEL14 following the dissociation of GroES7 must
      precede ADP release. These results explain how the GroEL14 cavity can become
      reversibly accessible to proteins under in vivo conditions that favor 2:1
      complexes.

PMID- 10077572
TI  - Yeast flavin-containing monooxygenase generates oxidizing equivalents that
      control protein folding in the endoplasmic reticulum.
AB  - The flavin-containing monooxygenase from yeast (yFMO) catalyzes the O2- and NADPH
      dependent oxidations of biological thiols, including oxidation of glutathione to
      glutathione disulfide (GSSG). Glutathione and GSSG form the principle redox
      buffering system in the cell, with the endoplasmic reticulum (ER) being more
      oxidizing than the cytoplasm. Proper folding of disulfide-bonded proteins in the
      ER depends on an optimum redox buffer ratio. Here we show that yFMO is localized
      to the cytoplasmic side of the ER membrane. We used a gene knockout strain and
      expression vectors to show that yFMO has a major effect on the generation of GSSG
      transported into the ER. The enzyme is required for the proper folding, in the
      ER, of test proteins with disulfide bonds, whereas those without disulfide bonds
      are properly folded independently of yFMO in the ER or in the cytoplasm.

PMID- 10077573
TI  - Identification of a transcription factor, encoded by two vaccinia virus early
      genes, that regulates the intermediate stage of viral gene expression.
AB  - Vaccinia virus early, intermediate, and late stage genes are sequentially
      transcribed by the viral RNA polymerase within the cytoplasm of infected cells.
      We found that the 34- and 45-kDa polypeptides encoded by vaccinia virus ORFs A8R
      and A23R, respectively, were necessary to reconstitute transcription of a
      template with an intermediate stage promoter. Coexpression of the A8R and A23R
      genes in Escherichia coli was required for in vitro activity. In addition, the
      two polypeptides copurified, indicating their association as protein subunits of
      a vaccinia virus intermediate transcription factor. This factor, which we named
      VITF-3, complemented three viral proteins-namely, the RNA polymerase, capping
      enzyme, and a 30-kDa protein called VITF-1 that is also a subunit of the RNA
      polymerase-and an unidentified cell factor called VITF-2. Expression of the A8R
      and A23R genes occurred between 1 and 5 h after vaccinia virus infection and was
      not prevented by an inhibitor of DNA replication, consistent with a role for VITF
      3 in specifically regulating intermediate transcription in vivo. The vaccinia
      virus A8R and A23R genes are highly conserved among vertebrate poxviruses, but no
      other viral or cellular homologs were identified.

PMID- 10077574
TI  - A strategy for rapid sequencing of heparan sulfate and heparin saccharides.
AB  - Sulfated glycosaminoglycans (GAGs) are linear polysaccharides of repeating
      disaccharide sequences on which are superimposed highly complex and variable
      patterns of sulfation, especially in heparan sulfate (HS). HS and the
      structurally related heparin exert important biological functions, primarily by
      interacting with proteins and regulating their activities. Evidence is
      accumulating that these interactions depend on specific saccharide sequences, but
      the lack of simple, direct techniques for sequencing GAG saccharides has been a
      major obstacle to progress. We describe how HS and heparin saccharides can be
      sequenced rapidly by using an integrated strategy with chemical and enzymic
      steps. Attachment of a reducing-end fluorescent tag establishes a reading frame.
      Partial selective chemical cleavage at internal N-sulfoglucosamine residues with
      nitrous acid then creates a set of fragments of defined sizes. Subsequent
      digestion of these fragments with combinations of exosulfatases and
      exoglycosidases permits the selective removal of specific sulfates and
      monosaccharides from their nonreducing ends. PAGE of the products yields a
      pattern of fluorescent bands from which the saccharide sequence can be read
      directly. Data are presented on sequencing of heparin tetrasaccharides and
      hexasaccharides of known structure; these data show the accuracy and versatility
      of this sequencing strategy. Data also are presented on the application of the
      strategy to the sequencing of an HS decasaccharide of unknown structure.
      Application and further development of this sequencing strategy, called integral
      glycan sequencing, will accelerate progress in defining the structure-activity
      relationships of these complex GAGs and lead to important insights into their
      biological functions.

PMID- 10077575
TI  - HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for
      virus replication.
AB  - Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a crucial
      role for this protein in several functions related to viral replication,
      including viral assembly. It has been suggested that Gag may fulfill some of the
      functions by recruiting host cellular protein(s). In our effort to identify
      structural and functional homologies between Gag and cellular cytoskeletal and
      secretory proteins involved in transport, we observed that HIV-1 Gag contains a
      unique PGQM motif in the capsid region. This motif was initially noted in the
      regulatory domain of synexin the membrane fusion protein of Xenopus laevis. To
      evaluate the functional significance of the highly conserved PGQM motif, we
      introduced alanine (A) in place of individual residues of the PGQM and deleted
      the motif altogether in a Gag expression plasmid and in an HIV-1 proviral DNA.
      The proviral DNA containing mutations in the PGQM motif showed altered
      expression, assembly, and release of viral particles in comparison to parental
      (NL4-3) DNA. When tested in multiple- and single-round replication assays, the
      mutant viruses exhibited distinct replication phenotypes; the viruses containing
      the A for the G and Q residues failed to replicate, whereas A in place of the P
      and M residues did not inhibit viral replication. Deletion of the tetrapeptide
      also resulted in the inhibition of replication. These results suggest that the
      PGQM motif may play an important role in the infection process of HIV-1 by
      facilitating protein-protein interactions between viral and/or viral and cellular
      proteins.

PMID- 10077576
TI  - Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src
      substrate during mitosis.
AB  - Sam68, the 68-kDa Src substrate associated during mitosis, is an RNA-binding
      protein with signaling properties that contains a GSG (GRP33, Sam68, GLD-1)
      domain. Here we report the cloning of two Sam68-like-mammalian proteins, SLM-1
      and SLM-2. These proteins have an approximately 70% sequence identity with Sam68
      in their GSG domain. SLM-1 and SLM-2 have the characteristic Sam68 SH2 and SH3
      domain binding sites. SLM-1 is an RNA-binding protein that is tyrosine
      phosphorylated by Src during mitosis. SLM-1 bound the SH2 and SH3 domains of
      p59(fyn), Grb-2, phospholipase Cgamma-1 (PLCgamma-1), and/or p120(rasGAP),
      suggesting it may function as a multifunctional adapter protein for Src during
      mitosis. SLM-2 is an RNA-binding protein that is not tyrosine phosphorylated by
      Src or p59(fyn). Moreover, SLM-2 did not associate with the SH3 domains of
      p59(fyn), Grb-2, PLCgamma-1, or p120(rasGAP), suggesting that SLM-2 may not
      function as an adapter protein for these proteins. The identification of SLM-1
      and SLM-2 demonstrates the presence of a Sam68/SLM family whose members have the
      potential to link signaling pathways with RNA metabolism.

PMID- 10077577
TI  - Iron availability dramatically alters the distribution of ferritin subunit
      messages in Drosophila melanogaster.
AB  - Insect ferritins have subunits homologous to the heavy and light chains of
      vertebrate ferritins. Cloning and sequence of the heavy chain homologue (HCH) of
      Drosophila melanogaster ferritin subunit have been reported earlier. When
      Northern blots of D. melanogaster RNA were probed with a cDNA for this HCH, three
      bands were observed. It was shown that these represented at least four classes of
      mRNA of various lengths. The polymorphism results from alternative splicing of an
      intron in the 5' untranslated region (UTR) that contains the iron-responsive
      element (IRE) and from two alternative polyadenylation sites in the 3' UTR. This
      has also been reported by others [Lind, M. I., Ekengren, S., Melefors, O. &
      Soderhall, K. (1998) FEBS Lett. 436, 476-482]. By hybridizing Northern blots with
      specific probes, it has been shown that the relative proportions of the messages
      vary with the life stage and especially with iron supplementation of the diet.
      Iron significantly increases the amount of ferritin HCH messages and dramatically
      shifts the balance toward those messages that lack an IRE and/or have a short 3'
      UTR. In the larvae this change takes place in the gut, but not in the fat body.
      We speculate that this dramatic shift in message distribution may result from an
      effect of iron on the rate of transcription or message degradation, or from an
      effect on the splicing process itself. Synthesis of ferritin HCH subunit mRNAs
      that lack an IRE may be important under conditions of iron overload.

PMID- 10077578
TI  - Tissue-specific processing of cocaine- and amphetamine-regulated transcript
      peptides in the rat.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered
      hypothalamic peptide regulated by leptin and with a potent appetite-suppressing
      activity. In the rat, the CART gene encodes a peptide of 116 amino acid residues
      (or a splice variant 13 residues longer). The predicted signal sequence is 27
      amino acid residues, resulting in a prohormone of 89 residues. The CART
      prohormone contains several potential posttranslational processing sites in the
      form of mono- and dibasic sequences. In the present study we have purified CART
      peptides from extracts of adrenal gland, hypothalamus, nucleus accumbens, and
      pituitary gland (anterior and neurointermediate lobe) of the rat and determined
      the peptide structures by using microsequencing and mass spectrometry. In none of
      the tissues examined the long splice variant was found. From the adrenal gland,
      the CART(1-89) and CART(10-89) peptides were isolated, in contrast to the
      hypothalamus and nucleus accumbens, from which the shorter form peptides CART(42
      89) and CART(49-89) were purified. From the anterior lobe of the pituitary gland,
      CART(42-89) was isolated, in contrast to the neurointermediate lobe, which
      contains only CART(49-89). This tissue-specific processing indicates that CART
      peptides may have different biological functions in the periphery and in the
      central nervous system.

PMID- 10077579
TI  - Specific interaction of Tat with the human but not rodent P-TEFb complex mediates
      the species-specific Tat activation of HIV-1 transcription.
AB  - Tat stimulation of HIV-1 transcriptional elongation is species-specific and is
      believed to require a specific cellular cofactor present in many human and
      primate cells but not in nonpermissive rodent cells. Human P-TEFb, composed of
      Cdk9 and cyclin T1, is a general transcription elongation factor that
      phosphorylates the C-terminal domain of RNA polymerase II. Previous studies have
      also implicated P-TEFb as a Tat-specific cellular cofactor and, in particular,
      human cyclin T1 as responsible for the species-specific Tat activation. To obtain
      functional evidence in support of these hypotheses, we generated and examined the
      activities of human-rodent "hybrid" P-TEFb complexes. We found that P-TEFb
      complexes containing human cyclin T1 complexed with either human or rodent Cdk9
      supported Tat transactivation and interacted with the Tat activation domain and
      the HIV-1 TAR RNA element to form TAR loop-dependent ribonucleoprotein complexes.
      Although a stable complex containing rodent cyclin T1 and human Cdk9 was capable
      of phosphorylating CTD and mediating basal HIV-1 elongation, it failed to
      interact with Tat and to mediate Tat transactivation, indicating that the
      abilities of P-TEFb to support basal elongation and Tat activation can be
      separated. Together, our data indicated that the specific interaction of human P
      TEFb with Tat/TAR, mostly through cyclin T1, is crucial for P-TEFb to mediate a
      Tat-specific and species-restricted activation of HIV-1 transcription. Amino acid
      residues unique to human Cdk9 also contributed partially to the formation of the
      P-TEFb-Tat-TAR complex. Moreover, the cyclin box of cyclin T1 and its immediate
      flanking region are largely responsible for the specific P-TEFb-Tat interaction.

PMID- 10077580
TI  - In vitro suicide inhibition of self-splicing of a group I intron from
      Pneumocystis carinii by an N3' --> P5' phosphoramidate hexanucleotide.
AB  - Binding enhancement by tertiary interactions is a strategy that takes advantage
      of the higher order folding of functionally important RNAs to bind short nucleic
      acid-based compounds tightly and more specifically than possible by simple base
      pairing. For example, tertiary interactions enhance binding of specific hexamers
      to a group I intron ribozyme from the opportunistic pathogen Pneumocystis carinii
      by 1,000- to 100,000-fold relative to binding by only base pairing. One such
      hexamer, d(AnTnGnAnCn)rU, contains an N3' --> P5' phosphoramidate deoxysugar
      phosphate backbone (n) that is resistant to chemical and enzymatic decay. Here,
      it is shown that this hexamer is also a suicide inhibitor of the intron's self
      splicing reaction in vitro. The hexamer is ligated in trans to the 3' exon of the
      precursor, producing dead-end products. At 4 mM Mg2+, the fraction of trans
      spliced product is greater than normally spliced product at hexamer
      concentrations as low as 200 nM. This provides an additional level of specificity
      for compounds that can exploit the catalytic potential of complexes with RNA
      targets.

PMID- 10077581
TI  - Mutation analysis of the Pip interaction domain reveals critical residues for
      protein-protein interactions.
AB  - The PU.1 interaction partner (Pip) is a member of the interferon regulatory
      factor family that regulates gene expression through heterodimerization with the
      ETS transcription factor PU.1. Binding of Pip alone to DNA is weak, and usually
      it is recruited by phosphorylated PU.1 to form a strong ternary complex with
      specific DNA sequences. An approach combining sequence homology analysis,
      secondary structure predictions, and a precise mutational strategy has been used
      to determine critical residues within the Pip heterodimerization domain that
      contribute to ternary complex formation. We have delimited the Pip interaction
      domain to residues 245-422 by using deletion analysis. Site-directed mutagenesis
      of conserved polar amino acids within two predicted alpha-helices contained in
      this region, and which are highly conserved in the IRF family, confirmed the
      importance of these residues for Pip-PU.1 interaction with DNA as well as for
      trans-activation activity. Our results suggest the existence of a functional
      epitope essential for heterodimerization between Pip and PU.1 and possibly, in
      general, between interferon regulatory factor family members and their partners.

PMID- 10077582
TI  - Phosphorylating DNA with DNA.
AB  - Nearly 50 individual DNAs with polynucleotide kinase-like activity were isolated
      from a random-sequence pool by using in vitro selection. Each self
      phosphorylating deoxyribozyme makes use of one or more of the eight standard NTPs
      or dNTPs as a source of activated phosphate. Although most prototypic
      deoxyribozymes poorly differentiate between the ribose and deoxyribose moieties,
      further optimization by in vitro selection produced variants that display up to
      100-fold discrimination between related NTP and dNTP substrates. An optimized ATP
      dependent deoxyribozyme uses ATP >40,000-fold more efficiently than CTP, GTP, or
      UTP. This enzyme operates with a rate enhancement of nearly one billion-fold over
      the uncatalyzed rate of ATP hydrolysis. A bimolecular version of the ATP
      dependent deoxyribozyme was further engineered to phosphorylate specific target
      DNAs with multiple turnover. The substrate-recognition patterns and rate
      enhancements intrinsic to these DNAs are characteristic of naturally occurring
      RNA and protein enzymes, supporting the hypothesis that DNA has sufficient
      catalytic potential to function as an enzyme in biological systems.

PMID- 10077583
TI  - Structural basis for the inhibitory effect of brefeldin A on guanine nucleotide
      exchange proteins for ADP-ribosylation factors.
AB  - Protein secretion through the endoplasmic reticulum and Golgi vesicular
      trafficking system is initiated by the binding of ADP-ribosylation factors (ARFs)
      to donor membranes, leading to recruitment of coatomer, bud formation, and
      eventual vesicle release. ARFs are approximately 20-kDa GTPases that are active
      with bound GTP and inactive with GDP bound. Conversion of ARF-GDP to ARF-GTP is
      regulated by guanine nucleotide-exchange proteins. All known ARF guanine
      nucleotide-exchange proteins contain a Sec7 domain of approximately 200 amino
      acids that includes the active site and fall into two classes that differ in
      molecular size and susceptibility to inhibition by the fungal metabolite
      brefeldin A (BFA). To determine the structural basis of BFA sensitivity, chimeric
      molecules were constructed by using sequences from the Sec7 domains of BFA
      sensitive yeast Sec7 protein (ySec7d) and the insensitive human cytohesin-1 (C
      1Sec7). Based on BFA inhibition of the activities of these molecules with
      recombinant yeast ARF2 as substrate, the Asp965-Met975 sequence in ySec7d was
      shown to be responsible for BFA sensitivity. A C-1Sec7 mutant in which Ser199,
      Asn204, and Pro209 were replaced with the corresponding ySec7d amino acids,
      Asp965, Gln970, and Met975, exhibited BFA sensitivity similar to that of
      recombinant ySec7d (rySec7d). Single replacement in C-1Sec7 of Ser199 or Pro209
      resulted in partial inhibition by BFA, whereas replacement of Gln970 in ySec7d
      with Asn (as found in C-1Sec7) had no effect. As predicted, the double C-1Sec7
      mutant with S199D and P209M was BFA-sensitive, demonstrating that Asp965 and
      Met975 in ySec7d are major molecular determinants of BFA sensitivity.

PMID- 10077584
TI  - Toward controlling gene expression at will: selection and design of zinc finger
      domains recognizing each of the 5'-GNN-3' DNA target sequences.
AB  - We have taken a comprehensive approach to the generation of novel DNA binding
      zinc finger domains of defined specificity. Herein we describe the generation and
      characterization of a family of zinc finger domains developed for the recognition
      of each of the 16 possible 3-bp DNA binding sites having the sequence 5'-GNN-3'.
      Phage display libraries of zinc finger proteins were created and selected under
      conditions that favor enrichment of sequence-specific proteins. Zinc finger
      domains recognizing a number of sequences required refinement by site-directed
      mutagenesis that was guided by both phage selection data and structural
      information. In many cases, residues not expected to make base-specific contacts
      had effects on specificity. A number of these domains demonstrate exquisite
      specificity and discriminate between sequences that differ by a single base with
      >100-fold loss in affinity. We conclude that the three helical positions -1, 3,
      and 6 of a zinc finger domain are insufficient to allow for the fine specificity
      of the DNA binding domain to be predicted. These domains are functionally modular
      and may be recombined with one another to create polydactyl proteins capable of
      binding 18-bp sequences with subnanomolar affinity. The family of zinc finger
      domains described here is sufficient for the construction of 17 million novel
      proteins that bind the 5'-(GNN)6-3' family of DNA sequences. These materials and
      methods should allow for the rapid construction of novel gene switches and
      provide the basis for a universal system for gene control.

PMID- 10077585
TI  - An activation-specific role for transcription factor TFIIB in vivo.
AB  - A yeast mutant was isolated encoding a single amino acid substitution [serine-53 
      -> proline (S53P)] in transcription factor TFIIB that impairs activation of the
      PHO5 gene in response to phosphate starvation. This effect is activation-specific
      because S53P did not affect the uninduced level of PHO5 expression, yet is not
      specific to PHO5 because Adr1-mediated activation of the ADH2 gene also was
      impaired by S53P. Pho4, the principal activator of PHO5, directly interacted with
      TFIIB in vitro, and this interaction was impaired by the S53P replacement.
      Furthermore, Pho4 induced a conformational change in TFIIB, detected by enhanced
      sensitivity to V8 protease. The S53P replacement also impaired activation of a
      lexA(op)-lacZ reporter by a LexA fusion protein to the activation domain of Adr1,
      thereby indicating that the transcriptional effect on ADH2 expression is specific
      to the activation function of Adr1. These results define an activation-specific
      role for TFIIB in vivo and suggest that certain activators induce a
      conformational change in TFIIB as part of their mechanism of transcriptional
      stimulation.

PMID- 10077586
TI  - Molecular model of muscle contraction.
AB  - A quantitative stochastic model of the mechanochemical cycle of myosin, the
      protein that drives muscle contraction, is proposed. It is based on three
      premises: (i) the myosin head incorporates a lever arm, whose equilibrium
      position adjusts as each of the products of ATP hydrolysis dissociates from the
      nucleotide pocket; (ii) the chemical reaction rates are modified according to the
      work done in moving the arm; and (iii) the compliance of myosin's elastic element
      is designed to permit many molecules to work together efficiently. The model has
      a minimal number of parameters and provides an explanation, at the molecular
      level, of many of the mechanical and thermodynamic properties of steadily
      shortening muscle. In particular, the inflexion in the force-velocity curve at a
      force approaching the isometric load is reproduced. Moreover, the model indicates
      that when large numbers of myosin molecules act collectively, their chemical
      cycles can be synchronized, and that this leads to stepwise motion of the thin
      filament. The oscillatory transient response of muscle to abrupt changes of load
      is interpreted in this light.

PMID- 10077587
TI  - Interpretation of the spatial charge displacements in bacteriorhodopsin in terms
      of structural changes during the photocycle.
AB  - We have recently introduced a method, made possible by an improved orienting
      technique using a combination of electric and magnetic fields, that allows the
      three-dimensional detection of the intramolecular charge displacements during the
      photocycle of bacteriorhodopsin. This method generates electric asymmetry, a
      prerequisite for the detection of electric signal on the macroscopic sample, in
      all three spatial dimensions. Purple membrane fragments containing
      bacteriorhodopsin were oriented so that their permanent electric dipole moment
      vectors were perpendicular to the membrane plane and pointed in the same
      direction. The resulting cylindrical symmetry was broken by photoselection, i.
      e., by flash excitation with low intensity linearly polarized light. From the
      measured electric signals, the three-dimensional motion of the electric charge
      center in the bacteriorhodopsin molecules was calculated for the first 400
      microseconds. Simultaneous absorption kinetic recording provided the time
      dependent concentrations of the intermediates. Combining the two sets of data, we
      determined the discrete dipole moments of intermediates up to M. When compared
      with the results of current molecular dynamics calculations, the data provided a
      decisive experimental test for selecting the optimal theoretical model for the
      proton transport and should eventually lead to a full description of the
      mechanism of the bacteriorhodopsin proton pump.

PMID- 10077588
TI  - Multiple pathways on a protein-folding energy landscape: kinetic evidence.
AB  - The funnel landscape model predicts that protein folding proceeds through
      multiple kinetic pathways. Experimental evidence is presented for more than one
      such pathway in the folding dynamics of a globular protein, cytochrome c. After
      photodissociation of CO from the partially denatured ferrous protein, fast time
      resolved CD spectroscopy shows a submillisecond folding process that is complete
      in approximately 10(-6) s, concomitant with heme binding of a methionine residue.
      Kinetic modeling of time-resolved magnetic circular dichroism data further
      provides strong evidence that a 50-microseconds heme-histidine binding process
      proceeds in parallel with the faster pathway, implying that Met and His binding
      occur in different conformational ensembles of the protein, i.e., along
      respective ultrafast (microseconds) and fast (milliseconds) folding pathways.
      This kinetic heterogeneity appears to be intrinsic to the diffusional nature of
      early folding dynamics on the energy landscape, as opposed to the late-time
      heterogeneity associated with nonnative heme ligation and proline isomers in
      cytochrome c.

PMID- 10077589
TI  - Estradiol induces the calcium-dependent translocation of endothelial nitric oxide
      synthase.
AB  - Although estrogen is known to stimulate nitric oxide synthesis in vascular
      endothelium, the molecular mechanisms responsible for this effect remain to be
      elucidated. Using quantitative immunofluorescence imaging approaches, we have
      investigated the effect of estradiol on the subcellular targeting of endothelial
      nitric oxide synthase (eNOS) in bovine aortic endothelial cells. In unstimulated
      endothelial cells, eNOS is predominantly localized at the cell membrane. Within 5
      min after the addition of estradiol, most of the eNOS translocates from the
      membrane to intracellular sites close to the nucleus. On more prolonged exposure
      to estradiol, most of the eNOS returns to the membrane. This effect of estradiol
      is evident at a concentration of 1 pM, and a maximal estradiol effect is seen at
      a concentration of 1 nM. Neither progesterone nor testosterone has any effect on
      eNOS distribution. After estradiol addition, a transient rise in intracellular
      Ca2+ concentration precedes eNOS translocation. Both the Ca2+-mobilizing and eNOS
      translocating effects of estradiol are completely blocked by the estrogen
      receptor antagonist ICI 182,780, and the intracellular Ca2+ chelator 1,2-bis-(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) prevents estradiol-induced
      eNOS translocation. Use of the nitric oxide-specific dye diaminofluorescein shows
      that estradiol treatment increases nitric oxide generation by endothelial cells;
      this response is blocked by ICI 182,780 and by the eNOS inhibitor Nomega-nitro-L
      arginine. These results show that estradiol induces subcellular translocation of
      eNOS by a rapid, Ca2+-dependent, receptor-mediated mechanism, and they suggest a
      nongenomic role for estrogen in the modulation of NO-dependent vascular tone.

PMID- 10077590
TI  - The Opitz syndrome gene product, MID1, associates with microtubules.
AB  - Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by
      defects of the ventral midline, including hypertelorism, cleft lip and palate,
      heart defects, and mental retardation. We recently identified the gene
      responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a
      member of the RING finger family. These proteins are characterized by an N
      terminal tripartite protein-protein interaction domain and a conserved C terminus
      of unknown function. Unlike other RING finger proteins for which diverse cellular
      functions have been proposed, the function of MID1 is as yet undefined. By using
      the green fluorescent protein as a tag, we show here that MID1 is a microtubule
      associated protein that influences microtubule dynamics in MID1-overexpressing
      cells. We confirm this observation by demonstrating a colocalization of MID1 and
      tubulin in subcellular fractions and the association of endogenous MID1 with
      microtubules after in vitro assembly. Furthermore, overexpressed MID1 proteins
      harboring mutations described in OS patients lack the capability to associate
      with microtubules, forming cytoplasmic clumps instead. These data give an idea of
      the possible molecular pathomechanism underlying the OS phenotype.

PMID- 10077591
TI  - DNA replication in vertebrates requires a homolog of the Cdc7 protein kinase.
AB  - CDC7 is an essential gene required for DNA replication in Saccharomyces
      cerevisiae. Cdc7p homologs have recently been identified in vertebrates, but
      their role in DNA replication has not yet been addressed. Here we show that
      antibodies to the Xenopus laevis homolog, xCdc7, interfere with DNA replication
      in vivo in developing embryos and in vitro in cycling egg extracts. We also
      demonstrate cell cycle-dependent association of xCdc7 with the Mcm complex, which
      binds to replication origins and also is required for DNA synthesis. Taken
      together, these data indicate that the function of xCdc7 is conserved from fungi
      to vertebrates. xCdc7 protein accumulates after stimulation of resting oocytes
      with progesterone, suggesting a molecular explanation for previous observations
      that the development of the capacity for DNA replication requires protein
      synthesis late in meiosis I.

PMID- 10077592
TI  - Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the
      assembly of focal adhesions and actin stress fibers.
AB  - The assembly of focal adhesions and actin stress fibers by cells plated on
      fibronectin depends on adhesion-mediated signals involving both integrins and
      cell-surface heparan sulfate proteoglycans. These two cell-surface receptors
      interact with different domains of fibronectin. To attempt to identify the
      heparan sulfate proteoglycans involved, we used fibronectin-null (FN-/-) mouse
      fibroblasts to eliminate the contribution of endogenous fibronectin during the
      analysis. FN-/- fibroblasts plated on the cell-binding domain of fibronectin or
      on antibodies directed against mouse beta1 integrin chains attach but fail to
      spread and do not form focal adhesions or actin stress fibers. When such cells
      are treated with antibodies directed against the ectodomain of mouse syndecan-4,
      they spread fully and assemble focal adhesions and actin stress fibers
      indistinguishable from those seen in cells plated on intact fibronectin. These
      results identify syndecan-4 as a heparan sulfate proteoglycan involved in the
      assembly process. The antibody-stimulated assembly of focal adhesions and actin
      stress fibers in cells plated on the cell-binding domain of fibronectin can be
      blocked with C3 exotransferase, an inhibitor of the small GTP-binding protein
      Rho. Treatment of cells with lysophosphatidic acid, which activates Rho, results
      in full spreading and assembly of focal adhesions and actin stress fibers in
      fibroblasts plated on the cell-binding domain of fibronectin. We conclude that
      syndecan-4 and integrins can act cooperatively in generating signals for cell
      spreading and for the assembly of focal adhesions and actin stress fibers. We
      conclude further that these joint signals are regulated in a Rho-dependent
      manner.

PMID- 10077593
TI  - Angiostatin binds ATP synthase on the surface of human endothelial cells.
AB  - Angiostatin, a proteolytic fragment of plasminogen, is a potent antagonist of
      angiogenesis and an inhibitor of endothelial cell migration and proliferation. To
      determine whether the mechanism by which angiostatin inhibits endothelial cell
      migration and/or proliferation involves binding to cell surface plasminogen
      receptors, we isolated the binding proteins for plasminogen and angiostatin from
      human umbilical vein endothelial cells. Binding studies demonstrated that
      plasminogen and angiostatin bound in a concentration-dependent, saturable manner.
      Plasminogen binding was unaffected by a 100-fold molar excess of angiostatin,
      indicating the presence of a distinct angiostatin binding site. This finding was
      confirmed by ligand blot analysis of isolated human umbilical vein endothelial
      cell plasma membrane fractions, which demonstrated that plasminogen bound to a 44
      kDa protein, whereas angiostatin bound to a 55-kDa species. Amino-terminal
      sequencing coupled with peptide mass fingerprinting and immunologic analyses
      identified the plasminogen binding protein as annexin II and the angiostatin
      binding protein as the alpha/beta-subunits of ATP synthase. The presence of this
      protein on the cell surface was confirmed by flow cytometry and
      immunofluorescence analysis. Angiostatin also bound to the recombinant alpha
      subunit of human ATP synthase, and this binding was not inhibited by a 2,500-fold
      molar excess of plasminogen. Angiostatin's antiproliferative effect on
      endothelial cells was inhibited by as much as 90% in the presence of anti-alpha
      subunit ATP synthase antibody. Binding of angiostatin to the alpha/beta-subunits
      of ATP synthase on the cell surface may mediate its antiangiogenic effects and
      the down-regulation of endothelial cell proliferation and migration.

PMID- 10077594
TI  - Cyclin-dependent kinase control of centrosome duplication.
AB  - Centrosomes nucleate microtubules and duplicate once per cell cycle. This
      duplication and subsequent segregation in mitosis results in maintenance of the
      one centrosome/cell ratio. Centrosome duplication occurs during the G1/S
      transition in somatic cells and must be coupled to the events of the nuclear cell
      cycle; failure to coordinate duplication and mitosis results in abnormal numbers
      of centrosomes and aberrant mitoses. Using both in vivo and in vitro assays, we
      show that centrosome duplication in Xenopus laevis embryos requires cyclin/cdk2
      kinase activity. Injection of the cdk (cyclin-dependent kinase) inhibitor p21
      into one blastomere of a dividing embryo blocks centrosome duplication in that
      blastomere; the related cdk inhibitor p27 has a similar effect. An in vitro
      system using Xenopus extracts carries out separation of the paired centrioles
      within the centrosome. This centriole separation activity is dependent on
      cyclin/cdk2 activity; depletion of either cdk2 or of the two activating cyclins,
      cyclin A and cyclin E, eliminates centriole separation activity. In addition,
      centriole separation is inhibited by the mitotic state, suggesting a mechanism of
      linking the cell cycle to periodic duplication of the centrosome.

PMID- 10077595
TI  - Histidine-tagged wild-type yeast actin: its properties and use in an approach for
      obtaining yeast actin mutants.
AB  - Wild-type and an N-terminal 6-histidine-tagged actin have each been expressed by
      using a yeast strain that contains the actin gene on a plasmid and not on the
      chromosome. Yeast strains have also been constructed that use two plasmids, one
      expressing the wild-type protein and the other the 6-histidine-tagged protein.
      Yeast cells can be grown with either plasmid alone or with both plasmids together
      and appear to be normal in that the growth rates of all the yeast strains are
      quite similar, as is the morphology of the yeast cells. The polymerization
      properties of the 6-histidine-tagged actin appear almost identical to wild-type
      actin expressed from the chromosome. When the wild-type and 6-histidine-tagged
      actin are coexpressed, they can be purified by standard techniques and then
      separated using nickel-nitrilotriacetate chromatography. The method can be used
      to prepare actin mutants including those that are nonfunctional or might not
      support yeast growth for other reasons.

PMID- 10077596
TI  - A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and
      blocks cell division.
AB  - A new ubiquitin-processing protease (Ubp-M) has been identified in mammalian
      cells that is phosphorylated at the onset of mitosis and dephosphorylated during
      the metaphase/anaphase transition. The carboxyl-terminal domain of this 823-aa
      protein can be phosphorylated in vitro with either extracts of mitotic cells or
      purified cdc-2/cyclin B complexes. Recombinant Ubp-M is able to deubiquitinate
      histone H2A in vitro, and the phosphorylated form is also enzymatically active.
      Wild-type Ubp-M, transiently expressed as green fluorescent protein-fusion
      proteins, localizes in the cytoplasm of cultured cells, but mutant forms, lacking
      an active-site cysteine, associate closely with mitotic chromosomes during all
      stages of cell division and remain within the nucleus during the postmitotic
      period. Cells transfected with plasmids containing mutant Ubp-M genes stop
      dividing and eventually undergo apoptosis. Ubp-M may deubiquitinate one or more
      critical proteins that are involved in the condensation of mitotic chromosomes,
      possibly acting selectively on histones H2A and H2B, the major ubiquitinated
      proteins of chromatin.

PMID- 10077597
TI  - Intermolecular interactions between dimeric calcium-sensing receptor monomers are
      important for its normal function.
AB  - We recently demonstrated that the G protein-coupled, extracellular calcium
      sensing receptor (CaR) forms disulfide-linked dimers. The functional significance
      of dimerization of this receptor was suggested by our earlier observations that
      CaRs carrying certain point mutations exert dominant negative effects on the
      function of the coexpressed wild-type receptor both in vivo and when
      cotransfected in human embryonic kidney cells. In this study, we explored the
      functional consequences of CaR dimerization. Coexpression in human embryonic
      kidney cells of specific pairs of mutant CaRs, each with reduced or absent
      activity because of distinct loss-of-function mutations, results in the formation
      of heterodimers and partially reconstitutes extracellular calcium-dependent
      signaling. Moreover, our results suggest that the CaR has at least two
      functionally separable domains. However, the presence of an abnormal domain in
      each mutant monomer substantially impairs the function of the CaR heterodimer,
      resulting in the reconstituted CaRs having characteristics distinct from those of
      the wild-type CaR. Our study suggests that intermolecular interactions within the
      dimeric CaR are important for the receptor's function.

PMID- 10077598
TI  - Identification of a putative effector protein for rab11 that participates in
      transferrin recycling.
AB  - We have identified and cloned the cDNA for a 912-aa protein, rab11BP, that
      interacts with the GTP-containing active form of rab11, a GTP-binding protein
      that plays a critical role in receptor recycling. Although rab11BP is primarily
      cytosolic, a significant fraction colocalizes with rab11 in endosomal membranes
      of both the sorting and recycling subcompartments. In vitro binding of rab11 to
      native rab11BP requires partial denaturation of the latter to expose an internal
      binding site located between residues 334 and 504 that is apparently masked by
      the C-terminal portion of the protein, which includes six repeats known as WD40
      domains. Within the cell, rab11BP must undergo a conformational change in which
      the rab11-binding site becomes exposed, because when coexpressed with rab11 in
      transfected cells the two proteins formed abundant complexes in association with
      membranes. Furthermore, although overexpression of rab11BP did not affect
      transferrin recycling, overexpression of a truncated form of the protein,
      rab11BP(1-504), that includes the rab11-binding site but lacks the WD40 domains
      inhibited recycling as strongly as does a dominant negative rab11 mutant protein
      that does not bind GTP. Strikingly, the inhibition caused by the truncated
      rab11BP was prevented completely when the cells also expressed a C-terminally
      deleted, nonprenylatable form of rab11 that, by itself, has no effect on
      recycling. We propose that rab11BP is an effector for rab11, whose association
      with this GTP-binding protein is dependent on the action of another membrane
      associated factor that promotes the unmasking of the rab11-binding site in
      rab11BP.

PMID- 10077599
TI  - Essential role of STAT3 for embryonic stem cell pluripotency.
AB  - Propagation of mouse embryonic stem (ES) cells in vitro requires exogenous
      leukemia inhibitory factor (LIF) or related cytokines. Potential downstream
      effectors of the LIF signal in ES cells include kinases of the Src, Jak, and
      mitogen-activated protein families and the signal transducer and transcriptional
      activator STAT3. Activation of nuclear STAT3 and the ability of ES cells to grow
      as undifferentiated clones were monitored during LIF withdrawal. A correlation
      was found between levels of STAT3 activity and maintenance of an undifferentiated
      phenotype at clonal density. In contrast, variation in STAT3 activity did not
      affect cell proliferation. The requirement for STAT3 was analyzed by targeted
      mutagenesis in ES cell lines exhibiting different degrees of LIF dependency. An
      insertional mutation was devised that abrogated Stat3 gene expression but could
      be reversed by Cre recombination-mediated excision. ES cells heterozygous for the
      Stat3 mutation could be isolated only from E14 cells, the line least dependent on
      LIF for self-renewal. Targeted clones isolated from other ES cell lines were
      invariably trisomic for chromosome 11, which carries the Stat3 locus, and
      retained normal levels of activated STAT3. Cre-regulated reduction of Stat3 gene
      copy number in targeted, euploid E14 clones resulted in dose-dependent losses of
      STAT3 activity and the efficiency of self-renewal without commensurate changes in
      cell cycle progression. These results demonstrate an essential role for a
      critical amount of STAT3 in the maintenance of an undifferentiated ES cell
      phenotype.

PMID- 10077600
TI  - The tail domain of lamin Dm0 binds histones H2A and H2B.
AB  - In multicellular organisms, the higher order organization of chromatin during
      interphase and the reassembly of the nuclear envelope during mitosis are thought
      to involve an interaction between the nuclear lamina and chromatin. The nuclear
      distribution of lamins and of peripheral chromatin is highly correlated in vivo,
      and lamins bind specifically to chromatin in vitro. Deletion mutants of
      Drosophila lamin Dm0 were expressed to map regions of the protein that are
      required for its binding to chromosomes. The binding activity requires two
      regions in the lamin Dm0 tail domain. The apparent Kd of binding of the lamin Dm0
      tail domain was found to be approximately 1 microM. Chromatin subfractions were
      examined to search for possible target molecules for the binding of lamin Dm0.
      Isolated polynucleosomes, nucleosomes, histone octamer, histone H2A/H2B dimer,
      and histones H2A or H2B displaced the binding of lamin Dm0 tail to chromosomes.
      This displacement was specific, because polyamines or proteins such as histones
      H1, H3, or H4 did not displace the binding of the lamin Dm0 tail to chromosomes.
      In addition, DNA sequences, including M/SARs, did not interfere with the binding
      of lamin Dm0 tail domain to chromosomes. Taken together, these results suggest
      that the interaction between the tail domain of lamin Dm0 and histones H2A and
      H2B may mediate the attachment of the nuclear lamina to chromosomes in vivo.

PMID- 10077601
TI  - Regulation of endogenous E2F1 stability by the retinoblastoma family proteins.
AB  - Certain E2F transcription factor species play a pivotal role in regulating cell
      cycle progression. The activity of E2F1, a protein with neoplastic transforming
      activity when unregulated, is tightly controlled at the transcriptional level
      during G0 exit. In addition, during this interval, the stability of endogenous
      E2F1 protein increased markedly. E2F1 stability also was dynamically regulated
      during myogenic differentiation and in response to gamma irradiation. One or more
      retinoblastoma family proteins likely participate in the stability process,
      because simian virus 40 T antigen disrupted E2F1 stability regulation during G1
      exit in a manner dependent on its ability to bind to pocket proteins. Thus,
      endogenous E2F1 function is regulated by both transcriptional and
      posttranscriptional control mechanisms.

PMID- 10077602
TI  - Molecular evidence of cryptic speciation in planktonic foraminifers and their
      relation to oceanic provinces.
AB  - The fossil record of planktonic foraminifers is a key source of data on the
      biodiversity and evolution of marine plankton. One of the most distinctive
      foraminiferal taxa, Orbulina universa, widely used as a stratigraphic and
      paleoclimatic index, has always been regarded as a single species. Here we
      present a phylogenetic analysis of Orbulina small subunit rDNA sequences from 25
      pelagic stations covering 100 degrees latitude in the Atlantic Ocean. The genetic
      data reveal the presence of three cryptic species, whose distribution is clearly
      correlated to hydrographic provinces, and particularly to sea-surface total
      chlorophyll a concentration. Our results, together with previous studies, suggest
      that a considerable part of the diversity among planktonic foraminifers has been
      overlooked in morphological taxonomies. Our data also support the idea that
      planktonic foraminifers, even if adapted to particular hydrographic conditions,
      are high-dispersal organisms whose speciation may be similar to that of other
      high-dispersal taxa in which reproductive mechanisms and behavior, rather than
      just geographic barriers to dispersal, play key roles in species formation and
      maintenance.

PMID- 10077603
TI  - CORE-SINEs: eukaryotic short interspersed retroposing elements with common
      sequence motifs.
AB  - A 65-bp "core" sequence is dispersed in hundreds of thousands copies in the human
      genome. This sequence was found to constitute the central segment of a group of
      short interspersed elements (SINEs), referred to as mammalian-wide interspersed
      repeats, that proliferated before the radiation of placental mammals. Here, we
      propose that the core identifies an ancient tRNA-like SINE element, which
      survived in different lineages such as mammals, reptiles, birds, and fish, as
      well as mollusks, presumably for >550 million years. This element gave rise to a
      number of sequence families (CORE-SINEs), including mammalian-wide interspersed
      repeats, whose distinct 3' ends are shared with different families of long
      interspersed elements (LINEs). The evolutionary success of the generic CORE-SINE
      element can be related to the recruitment of the internal promoter from highly
      transcribed host RNA as well as to its capacity to adapt to changing
      retropositional opportunities by sequence exchange with actively amplifying
      LINEs. It reinforces the notion that the very existence of SINEs depends on the
      cohabitation with both LINEs and the host genome.

PMID- 10077604
TI  - Relative rates of insertion and deletion mutations in a microsatellite sequence
      in cultured cells.
AB  - A cell culture system has been used to determine the relative rates of insertions
      and deletions of integral numbers of dinucleotide repeats in a microsatellite
      sequence. A plasmid was constructed that contained 17 repeats of poly(dC
      dA).poly(dG-dT) near the 5' end of a bacterial neomycin-resistance (neo) gene,
      such that the neo gene was translated in the (+1) reading frame. The plasmid was
      introduced into mismatch-repair-proficient and mismatch-repair-deficient
      mammalian cell lines. Rates of mutation to resistance to the neomycin analogue
      G418 were measured, and the nature of the mutations was determined. The mutations
      were all gains or losses of integral numbers of repeats, and mutations involving
      a single repeat greatly predominated over those involving multiple repeats. The
      data obtained from these studies were compared with results previously obtained
      with cells transfected with a similar plasmid in which the sequence of the
      oligonucleotide insert placed the neo gene in the (-1) reading frame. This
      experimental design made it possible to make direct comparisons between
      insertions and deletions of a single repeat unit. A significant excess of
      insertions over deletions was found in both repair-proficient and repair
      deficient cell lines, although the few mutations involving more than two repeats
      were deletions.

PMID- 10077605
TI  - GLI3 mutations in human disorders mimic Drosophila cubitus interruptus protein
      functions and localization.
AB  - Truncation mutations of the GLI3 zinc finger transcription factor can cause Greig
      cephalopolysyndactyly syndrome (GCPS), Pallister-Hall syndrome (PHS), and
      postaxial polydactyly type A (PAP-A). GLI3 is homologous to Drosophila Cubitus
      interruptus (Ci), which regulates the patched (ptc), gooseberry (gsb), and
      decapentaplegic (dpp) genes. Ci is sequestered in the cytoplasm and is subject to
      posttranslational processing whereby the full-length transcriptional activator
      form (Ci155) can be cleaved to a repressor form (Ci75). Under hedgehog signaling,
      the Ci155 form translocates to the nucleus whereas in the absence of hedgehog,
      the Ci75 form translocates to the nucleus. Based on the correlation of GLI3
      truncation mutations and the human phenotypes, we hypothesized that GLI3 shows
      transcriptional activation or repression activity and subcellular localization
      similar to Ci. Here we show that full-length GLI3 localizes to the cytoplasm and
      activates PTCH1 expression, which is similar to full-length Ci155. PHS mutant
      protein (GLI3-PHS) localizes to the nucleus and represses GLI3-activated PTCH1
      expression, which is similar to Ci75. The GCPS mutant protein has no effect on
      GLI3-activated PTCH1 transcription, consistent with the role of
      haploinsufficiency in this disorder. The PAP-A mutant protein (GLI3-PAP-A) showed
      less specific subcellular localization but still inhibited GLI3-activated PTCH1
      transcription, suggesting it may be a weaker allele than the GLI3-PHS mutation.
      These data show that GLI3 mutations in humans mimic functional effects of the
      Drosophila ci gene and correlate with the distinct effects of these mutations on
      human development.

PMID- 10077606
TI  - A cloning method to identify caspases and their regulators in yeast:
      identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP
      1.
AB  - Site-specific proteases play critical roles in regulating many cellular
      processes. To identify novel site-specific proteases, their regulators, and
      substrates, we have designed a general reporter system in Saccharomyces
      cerevisiae in which a transcription factor is linked to the intracellular domain
      of a transmembrane protein by protease cleavage sites. Here, we explore the
      efficacy of this approach by using caspases, a family of aspartate-specific
      cysteine proteases, as a model. Introduction of an active caspase into cells that
      express a caspase-cleavable reporter results in the release of the transcription
      factor from the membrane and subsequent activation of a nuclear reporter. We show
      that known caspases activate the reporter, that an activator of caspase activity
      stimulates reporter activation in the presence of an otherwise inactive caspase,
      and that caspase inhibitors suppress caspase-dependent reporter activity. We also
      find that, although low or moderate levels of active caspase expression do not
      compromise yeast cell growth, higher level expression leads to lethality. We have
      exploited this observation to isolate clones from a Drosophila embryo cDNA
      library that block DCP-1 caspase-dependent yeast cell death. Among these clones,
      we identified the known cell death inhibitor DIAP1. We showed, by using
      bacterially synthesized proteins, that glutathione S-transferase-DIAP1 directly
      inhibits DCP-1 caspase activity but that it had minimal effect on the activity of
      a predomainless version of a second Drosophila caspase, drICE.

PMID- 10077607
TI  - Periodical distribution of transcription factor sites in promoter regions and
      connection with chromatin structure.
AB  - Nucleosomes regulate transcriptional initiation when positioned in the promoter
      area. This may require the transcription factor (TF) sites to be correlated with
      the nucleosome positions and phased on the nucleosome surface. If this is the
      case, one would expect a periodical distribution of TF sites in the vicinity of
      promoters, with the nucleosomal period of 10.1-10.5 bp. We examined the
      distributions of putative binding sites of 323 different TFs along 1, 057
      sequences of the Eukaryotic Promoter Database (release 50) [Cavin Perier, R.,
      Junier, T. & Bucher, P. (1998) Nucleic Acids Res. 26, 353-357] and of 218 TFs on
      673 sequences of the Lead Exon Database of human promoter sequences. We obtained
      a statistically significant overrepresentation of TF sites distributed with the
      main period of 10.1-10.5 bp in the region -50 to +120 around the transcription
      start site and in few locations nearby. Correlation of the positioning of the TF
      sites with the nucleosomes is further reinforced by sequence-directed mapping of
      the nucleosomes, a method previously developed.

PMID- 10077608
TI  - The use of gene clusters to infer functional coupling.
AB  - Previously, we presented evidence that it is possible to predict functional
      coupling between genes based on conservation of gene clusters between genomes.
      With the rapid increase in the availability of prokaryotic sequence data, it has
      become possible to verify and apply the technique. In this paper, we extend our
      characterization of the parameters that determine the utility of the approach,
      and we generalize the approach in a way that supports detection of common classes
      of functionally coupled genes (e.g., transport and signal transduction clusters).
      Now that the analysis includes over 30 complete or nearly complete genomes, it
      has become clear that this approach will play a significant role in supporting
      efforts to assign functionality to the remaining uncharacterized genes in
      sequenced genomes.

PMID- 10077609
TI  - Leishmania major Friedlin chromosome 1 has an unusual distribution of protein
      coding genes.
AB  - Leishmania are evolutionarily ancient protozoans (Kinetoplastidae) and important
      human pathogens that cause a spectrum of diseases ranging from the asymptomatic
      to the lethal. The Leishmania genome is relatively small [ approximately 34
      megabases (Mb)], lacks substantial repetitive DNA, and is distributed among 36
      chromosomes pairs ranging in size from 0.3 Mb to 2.5 Mb, making it a useful
      candidate for complete genome sequence determination. We report here the
      nucleotide sequence of the smallest chromosome, chr1. The sequence of chr1 has a
      257-kilobase region that is densely packed with 79 protein-coding genes. This
      region is flanked by telomeric and subtelomeric repetitive elements that vary in
      number and content among the chr1 homologs, resulting in an approximately 27.5
      kilobase size difference. Strikingly, the first 29 genes are all encoded on one
      DNA strand, whereas the remaining 50 genes are encoded on the opposite strand.
      Based on the gene density of chr1, we predict a total of approximately 9,800
      genes in Leishmania, of which 40% may encode unknown proteins.

PMID- 10077610
TI  - Interpreting patterns of gene expression with self-organizing maps: methods and
      application to hematopoietic differentiation.
AB  - Array technologies have made it straightforward to monitor simultaneously the
      expression pattern of thousands of genes. The challenge now is to interpret such
      massive data sets. The first step is to extract the fundamental patterns of gene
      expression inherent in the data. This paper describes the application of self
      organizing maps, a type of mathematical cluster analysis that is particularly
      well suited for recognizing and classifying features in complex, multidimensional
      data. The method has been implemented in a publicly available computer package,
      GENECLUSTER, that performs the analytical calculations and provides easy data
      visualization. To illustrate the value of such analysis, the approach is applied
      to hematopoietic differentiation in four well studied models (HL-60, U937,
      Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were
      assayed, and an online database was created. GENECLUSTER was used to organize the
      genes into biologically relevant clusters that suggest novel hypotheses about
      hematopoietic differentiation-for example, highlighting certain genes and
      pathways involved in "differentiation therapy" used in the treatment of acute
      promyelocytic leukemia.

PMID- 10077611
TI  - Isolation of DNA fragments associated with methylated CpG islands in human
      adenocarcinomas of the lung using a methylated DNA binding column and denaturing
      gradient gel electrophoresis.
AB  - We have constructed a library of DNA fragments heavily methylated in human
      adenocarcinomas of the lung to permit the comprehensive isolation of methylated
      CpG islands in cancer. Heavily methylated genomic DNA fragments from tumors of
      nine male patients were enriched using a methylated DNA binding column and used
      for construction of the library. From this library, DNA fragments having
      properties of CpG islands were isolated on the basis of their reduced rate of
      strand dissociation during denaturing gradient gel electrophoresis. Approximately
      1,000 clones, corresponding to 0.3% of the library were analyzed, and nine DNA
      fragments were identified as being associated with CpG islands that were
      methylated in tumor DNA. One CpG island was methylated specifically in tumor DNA,
      whereas the remaining eight CpG islands were methylated both in normal and tumor
      DNA derived from the same patients. Our results suggest that the number of CpG
      islands methylated specifically in tumors is not large. The library, which
      contains DNA fragments from methylated CpG islands comprehensively, is expected
      to be valuable when elucidating epigenetic processes involved in carcinogenesis.

PMID- 10077612
TI  - Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome
      mutations.
AB  - To better understand the role of TBX5, a T-box containing transcription factor in
      forelimb and heart development, we have studied the clinical features of Holt
      Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to create
      null alleles caused substantial abnormalities both in limb and heart. In
      contrast, missense mutations produced distinct phenotypes: Gly80Arg caused
      significant cardiac malformations but only minor skeletal abnormalities; and
      Arg237Gln and Arg237Trp caused extensive upper limb malformations but less
      significant cardiac abnormalities. Amino acids altered by missense mutations were
      located on the three-dimensional structure of a related T-box transcription
      factor, Xbra, bound to DNA. Residue 80 is highly conserved within T-box sequences
      that interact with the major groove of target DNA; residue 237 is located in the
      T-box domain that selectively binds to the minor groove of DNA. These structural
      data, taken together with the predominant cardiac or skeletal phenotype produced
      by each missense mutation, suggest that organ-specific gene activation by TBX5 is
      predicated on biophysical interactions with different target DNA sequences.

PMID- 10077613
TI  - Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by
      a homolog of the PTEN tumor suppressor gene.
AB  - The human PTEN tumor suppressor gene is mutated in a wide variety of sporadic
      tumors. To determine the function of PTEN in vivo we have studied a PTEN homolog
      in Caenorhabditis elegans. We have generated a strong loss-of-function allele of
      the PTEN homolog and shown that the deficient strain is unable to enter dauer
      diapause. An insulin-like phosphatidylinositol 3-OH kinase (PI3'K) signaling
      pathway regulates dauer-stage entry. Mutations in either the daf-2 insulin
      receptor-like (IRL) gene or the age-1 encoded PI3'K catalytic subunit homolog
      cause constitutive dauer formation and also affect the life span, brood size, and
      metabolism of nondauer animals. Strikingly, loss-of-function mutations in the age
      1 PI3'K and daf-2 IRL genes are suppressed by loss-of-function mutations in the
      PTEN homolog. We establish that the PTEN homolog is encoded by daf-18, a
      previously uncloned gene that has been shown to interact genetically with the DAF
      2 IRL AGE-1 PI3'K signaling pathway. This interaction provides clear genetic
      evidence that PTEN acts to antagonize PI3'K function in vivo. Given the
      conservation of the PI3'K signaling pathway between C. elegans and mammals, the
      analysis of daf-18 PTEN mutant nematodes should shed light on the role of human
      PTEN in the etiology of metabolic disease, aging, and cancer.

PMID- 10077614
TI  - A zinc finger truncation of murine WT1 results in the characteristic urogenital
      abnormalities of Denys-Drash syndrome.
AB  - The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development,
      and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma,
      leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The
      analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash
      syndrome (DDS), can provide valuable insight concerning the role of WT1 in
      development and disease. DDS is a rare childhood disease characterized by a
      nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms
      tumor (WT). DDS patients are constitutionally heterozygous for exonic point
      mutations in WT1, which include mutations predicted to truncate the protein
      within the C-terminal zinc finger (ZF) region. We report that heterozygosity for
      a targeted murine Wt1 allele, Wt1(tmT396), which truncates ZF3 at codon 396,
      induces mesangial sclerosis characteristic of DDS in adult heterozygous and
      chimeric mice. Male genital defects also were evident and there was a single case
      of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9
      skipping event, implying a causal link between Wt1 dysfunction and Wilms
      tumorigenesis in mice. However, the mutant WT1(tmT396) protein accounted for only
      5% of WT1 in both heterozygous embryonic stem cells and the WT. This has
      implications regarding the mechanism by which the mutant allele exerts its
      effect.

PMID- 10077615
TI  - Detecting patterns of protein distribution and gene expression in silico.
AB  - Most biological information is contained within gene and genome sequences.
      However, current methods for analyzing these data are limited primarily to the
      prediction of coding regions and identification of sequence similarities. We have
      developed a computer algorithm, CoSMoS (for context sensitive motif searches),
      which adds context sensitivity to sequence motif searches. CoSMoS was challenged
      to identify genes encoding peroxisome-associated and oleate-induced genes in the
      yeast Saccharomyces cerevisiae. Specifically, we searched for genes capable of
      encoding proteins with a type 1 or type 2 peroxisomal targeting signal and for
      genes containing the oleate-response element, a cis-acting element common to
      fatty acid-regulated genes. CoSMoS successfully identified 7 of 8 known PTS
      containing peroxisomal proteins and 13 of 14 known oleate-regulated genes. More
      importantly, CoSMoS identified an additional 18 candidate peroxisomal proteins
      and 300 candidate oleate-regulated genes. Preliminary localization studies
      suggest that these include at least 10 previously unknown peroxisomal proteins.
      Phenotypic studies of selected gene disruption mutants suggests that several of
      these new peroxisomal proteins play roles in growth on fatty acids, one is
      involved in peroxisome biogenesis and at least two are required for synthesis of
      lysine, a heretofore unrecognized role for peroxisomes. These results expand our
      understanding of peroxisome content and function, demonstrate the utility of
      CoSMoS for context-sensitive motif scanning, and point to the benefits of
      improved in silico genome analysis.

PMID- 10077616
TI  - Polarity of recombination in transformation of Streptococcus pneumoniae.
AB  - In transformation of Streptococcus pneumoniae DNA enters the cell as single
      strand fragments and integrates into the chromosome by homologous recombination.
      Deletions and insertions of a few hundred base pairs frequently stop the
      recombination process of a donor strand. In this work we took advantage of such
      interruptions of recombination to compare the transformation efficiencies of the
      segments 5'- and 3'-ward from a deletion. The deletion was created in the center
      of a fragment of the ami locus, and sites around the deletion were labeled by a
      frameshift generating a restriction site. Heteroduplexes were constructed
      containing two restriction sites on one strand and two different ones on the
      complementary strand. ami+ bacteria were transformed with such heteroduplexes.
      ami- transformants were isolated and individually underwent amplification of the
      transformed ami region. We have obtained two kinds of amplification products:
      short when the deletion was integrated, long when recombination stops at the
      deletion. Each long fragment was tested by the four restriction enzymes to detect
      which strand and which side of the deletion had recombined. We found that 80% of
      the cuts were located 5' to the deletion, showing that, in vivo, the 5' side is
      strongly favored by recombination. Further results suggest that exchanges
      occurring from 5' to 3' relative to the donor strand are more efficient than in
      the opposite direction, thus accounting for the 5' preference.

PMID- 10077617
TI  - Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes.
AB  - The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T
      cell leukemia in humans. Its expression in these leukemias is activated by
      chromosomal translocations and inversions at 14q32.1. Here we report the
      isolation and characterization of a new member of the TCL1 gene family, TCL1b,
      located approximately 16 kb centromeric of TCL1. The 1.2-kb TCL1b cDNA encodes a
      14-kDa protein of 128 aa and shows 60% similarity to Tcl1. Expression profiles of
      TCL1 and TCL1b genes are very similar: both genes are expressed at very low
      levels in normal bone marrow and peripheral lymphocytes but are activated in T
      cell leukemia by rearrangements of the 14q32.1 region. Thus, translocations and
      inversions at 14q32. 1 in T cell malignancies involve two oncogenes.

PMID- 10077618
TI  - Mitotic recombination map of 13cen-13q14 derived from an investigation of loss of
      heterozygosity in retinoblastomas.
AB  - Loss of heterozygosity at tumor-suppressor loci is an important oncogenic
      mechanism first discovered in retinoblastomas. We explored this phenomenon by
      examining a set of matched retinoblastoma and leukocyte DNA samples from 158
      patients informative for DNA polymorphisms. Loss of heterozygosity at the
      retinoblastoma locus (13q14) was observed in 101 cases, comprising 7 cases with a
      somatic deletion causing hemizygosity and 94 with homozygosity (isodisomy).
      Homozygosity was approximately equally frequent in tumors from male and female
      patients, among patients with a germ-line vs. somatic initial mutation, and among
      patients in whom the initial mutation occurred on the maternal vs. paternal
      allele. A set of 75 tumors exhibiting homozygosity was investigated with markers
      distributed in the interval 13cen-13q14. Forty-one tumors developed homozygosity
      at all informative marker loci, suggesting that homozygosity occurred through
      chromosomal nondisjunction. The remaining cases exhibited mitotic recombination.
      There was no statistically significant bias in apparent nondisjunction vs.
      mitotic recombination among male vs. female patients or among patients with germ
      line vs. somatic initial mutations. We compared the positions of somatic
      recombination events in the analyzed interval with a previously reported meiotic
      recombination map. Although mitotic crossovers occurred throughout the assayed
      interval, they were more likely to occur proximally than a comparable number of
      meiotic crossovers. Finally, we observed four triple-crossover cases, suggesting
      negative interference for mitotic recombination, the opposite of what is usually
      observed for meiotic recombination.

PMID- 10077619
TI  - Organization of human and mouse skeletal myosin heavy chain gene clusters is
      highly conserved.
AB  - Myosin heavy chains (MyHCs) are highly conserved ubiquitous actin-based motor
      proteins that drive a wide range of motile processes in eukaryotic cells. MyHC
      isoforms expressed in skeletal muscles are encoded by a multigene family that is
      clustered on syntenic regions of human and mouse chromosomes 17 and 11,
      respectively. In an effort to gain a better understanding of the genomic
      organization of the skeletal MyHC genes and its effects on the regulation,
      function, and molecular genetics of this multigene family, we have constructed
      high-resolution physical maps of both human and mouse loci using PCR-based marker
      content mapping of P1-artificial chromosome clones. Genes encoding six MyHC
      isoforms have been mapped with respect to their linear order and transcriptional
      orientations within a 350-kb region in both human and mouse. These maps reveal
      that the order, transcriptional orientation, and relative intergenic distances of
      these genes are remarkably conserved between these species. Unlike many clustered
      gene families, this order does not reflect the known temporal expression patterns
      of these genes. However, the conservation of gene organization since the
      estimated divergence of these species (approximately 75-110 million years ago)
      suggests that the physical organization of these genes may be significant for
      their regulation and function.

PMID- 10077620
TI  - Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants.
AB  - We have cloned a mutS homolog from Drosophila melanogaster called spellchecker1
      (spel1) and have constructed spel1 mutant flies. MutS proteins promote the
      correction of DNA mismatches and serve important roles in DNA replication,
      recombination, and repair. The spel1 gene belongs to a subfamily of mutS first
      characterized by the MSH2 gene of yeast and which also includes hMSH2, one of the
      two major hereditary nonpolyposis colon cancer loci of humans. Like msh2 mutants
      in other species, we find that flies lacking the spel1 gene suffer a highly
      increased rate of instability in long runs of dinucleotide repeats when analyzed
      after 10-12 fly generations. Using a new assay, we have also discovered that
      mutations in spel1 decrease the stability of a dinucleotide repeat when it is
      copied into the site of a double-strand break during gene conversion. Contrary to
      the case in mammalian cells, spel1 deficiency does not affect tolerance of flies
      to a methylating agent nor does it affect resistance to gamma-irradiation.

PMID- 10077621
TI  - Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene.
AB  - Heterozygosity for germ-line mutations in the DNA mismatch repair gene MSH2
      predisposes humans to cancer. Here we use a highly sensitive reporter to describe
      a spontaneous mutator phenotype in diploid yeast cells containing a deletion of
      only one MSH2 allele. We also identify five MSH2 missense mutations that have
      dominant mutator effects in heterozygous cells when expressed at normal levels
      from the natural MSH2 promoter. For example, a 230-fold mutator effect is
      observed in an MSH2/msh2 diploid strain in which Gly693, which is invariant in
      MutS homologs and involved in ATP hydrolysis, is changed to alanine. DNA binding
      data suggest that mismatch repair is suppressed by binding of a mutant Msh2-Msh6
      heterodimer to a mismatch with subsequent inability to dissociate from the
      mismatch in the presence of ATP. A dominant mutator effect also is observed in
      yeast when Gly693 is changed to serine. An early onset colorectal tumor is
      heterozygous for the analogous Gly --> Ser mutation in hMSH2, and a second hMSH2
      mutation was not found, suggesting that this missense mutation may predispose to
      cancer via a dominant mutator effect. The mutator effects of the deletion mutant
      and the Gly --> Ala missense mutant in yeast MSH2 are enhanced by heterozygosity
      for a missense mutation in DNA polymerase delta that reduces its proofreading
      activity but is not a mutator in the heterozygous state. The synergistic effects
      of heterozygosity for mutations in two different genes that act in series to
      correct replication errors may be relevant to cancer predisposition.

PMID- 10077622
TI  - Functional differences between memory and naive CD8 T cells.
AB  - To determine how murine memory and naive T cells differ, we generated large
      numbers of long-lived memory CD8(+) T cells and compared them to naive cells
      expressing the same antigen-specific receptor (T cell receptor; TCR). Although
      both populations expressed similar levels of TCR and CD8, on antigen stimulation
      in vitro memory T cells down-regulated their TCR faster and more extensively and
      secreted IFN-gamma and IL-2 faster than naive T cells. Memory cells were also
      larger, and when freshly isolated from mice they contained perforin and killed
      target cells without having to be restimulated. They further differed from naive
      cells in requiring IL-15 for proliferation and in having a greater tendency to
      undergo apoptosis in vitro. On antigen stimulation in vivo, however, they
      proliferated more rapidly than naive cells. These findings suggest that, unlike
      naive T cells, CD8 memory T cells are intrinsically programmed to rapidly express
      their effector functions in vivo without having to undergo clonal expansion and
      differentiation.

PMID- 10077623
TI  - Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces
      autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4(+) T
      lymphocytes.
AB  - Many human and mouse tumor antigens are normal, nonmutated tissue differentiation
      antigens. Consequently, immunization with these "self" antigens could induce
      autoimmunity. When we tried to induce immune responses to five mouse melanocyte
      differentiation antigens, gp100, MART-1, tyrosinase, and tyrosinase-related
      proteins (TRP) 1 and TRP-2, we observed striking depigmentation and melanocyte
      destruction only in the skin of mice inoculated with a vaccinia virus encoding
      mouse TRP-1. These mice rejected a lethal challenge of B16 melanoma, indicating
      the immune response against TRP-1 could destroy both normal and malignant
      melanocytes. Cytotoxic T lymphocytes specific for TRP-1 could not be detected in
      depigmented mice, but high titers of IgG anti-TRP-1 antibodies were present.
      Experiments with knockout mice revealed an absolute dependence on major
      histocompatibility complex class II, but not major histocompatibility complex
      class I, for the induction of both vitiligo and tumor protection. Together, these
      results suggest that the deliberate induction of self-reactivity using a
      recombinant viral vector can lead to tumor destruction, and that in this model,
      CD4(+) T lymphocytes are an integral part of this process. Vaccine strategies
      targeting tissue differentiation antigens may be valuable in cancers arising from
      nonessential cells and organs such as melanocytes, prostate, testis, breast, and
      ovary.

PMID- 10077624
TI  - Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV
      1-based lentiviral vectors.
AB  - We compared the efficiency of transduction by an HIV-1-based lentiviral vector to
      that by a Moloney murine leukemia virus (MLV) retroviral vector, using stringent
      in vitro assays of primitive, quiescent human hematopoietic progenitor cells.
      Each construct contained the enhanced green fluorescent protein (GFP) as a
      reporter gene. The lentiviral vector, but not the MLV vector, expressed GFP in
      nondivided CD34(+) cells (45.5% GFP+) and in CD34(+)CD38(-) cells in G0 (12.4%
      GFP+), 48 hr after transduction. However, GFP could also be detected short-term
      in CD34(+) cells transduced with a lentiviral vector that contained a mutated
      integrase gene. The level of stable transduction from integrated vector was
      determined after extended long-term bone marrow culture. Both MLV vectors and
      lentiviral vectors efficiently transduced cytokine-stimulated CD34(+) cells. The
      MLV vector did not transduce more primitive, quiescent CD34(+)CD38(-) cells (n =
      8). In contrast, stable transduction of CD34(+)CD38(-) cells by the lentiviral
      vector was seen for over 15 weeks of extended long-term culture (9.2 +/- 5.2%, n
      = 7). GFP expression in clones from single CD34(+)CD38(-) cells confirmed
      efficient, stable lentiviral transduction in 29% of early and late-proliferating
      cells. In the absence of growth factors during transduction, only the lentiviral
      vector was able to transduce CD34(+) and CD34(+)CD38(-) cells (13.5 +/- 2.5%, n =
      11 and 12.2 +/- 9.7%, n = 4, respectively). The lentiviral vector is clearly
      superior to the MLV vector for transduction of quiescent, primitive human
      hematopoietic progenitor cells and may provide therapeutically useful levels of
      gene transfer into human hematopoietic stem cells.

PMID- 10077625
TI  - Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic
      lethality.
AB  - Mice lacking the RelA (p65) subunit of NF-kappaB die between days 14 and 15 of
      embryogenesis because of massive liver destruction. Fibroblasts and macrophages
      isolated from relA-/- embryos were found to be highly sensitive to tumor necrosis
      factor (TNF) cytotoxicity, raising the possibility that endogenous TNF is the
      cause of liver cell apoptosis. To test this idea, we generated mice lacking both
      TNF and RelA. Embryogenesis proceeds normally in such mice, and TNF/RelA double
      deficient mice are viable and have normal livers. Thus, the RelA-mediated
      antiapoptotic signal that protects normal cells from TNF injury in vitro can be
      shown to be operative in vivo.

PMID- 10077626
TI  - Position-dependent inhibition of class-switch recombination by PGK-neor cassettes
      inserted into the immunoglobulin heavy chain constant region locus.
AB  - The Ig heavy chain (IgH) constant region (CH) genes are organized from 5' to 3'
      in the order Cmicro, Cdelta, Cgamma3, Cgamma1, Cgamma2b, Cgamma2a, Cepsilon, and
      Calpha. Expression of CH genes downstream of Cdelta involves class-switch
      recombination (CSR), a process that is targeted by germ-line transcription (GT)
      of the corresponding CH gene. Previously, we demonstrated that insertion of a PGK
      neor cassette at two sites downstream of Calpha inhibits, in cultured B cells, GT
      of and CSR to a subset of CH genes (including Cgamma3, Cgamma2a, Cgamma2b, and
      Cepsilon) that lie as far as 120 kb upstream. Here we show that insertion of the
      PGK-neor cassette in place of sequences in the Igamma2b locus inhibits GT of and
      CSR to the upstream Cgamma3 gene, but has no major effect on the downstream
      Cgamma2a and Cepsilon genes. Moreover, replacement of the Cepsilon exons with a
      PGK-neor cassette in the opposite transcriptional orientation also inhibits, in
      culture, GT of and CSR to the upstream Cgamma3, Cgamma2b, and Cgamma2a genes. As
      with the PGK-neor insertions 3' of Calpha studied previously, the Cgamma1 and
      Calpha genes were less affected by these mutations both in culture and in mice,
      whereas the Cgamma2b gene appeared less affected in vivo. Our findings support
      the existence of a long-range 3' IgH regulatory region required for GT of and CSR
      to multiple CH genes and suggest that PGK-neor cassette insertion into the locus
      short circuits the ability of this region to facilitate GT of dependent CH genes
      upstream of the insertion.

PMID- 10077627
TI  - Cyclophilin C-associated protein: a normal secreted glycoprotein that down
      modulates endotoxin and proinflammatory responses in vivo.
AB  - Mouse cyclophilin C-associated protein (CyCAP) is a member of the scavenger
      receptor cysteine-rich domain superfamily and is 69% identical to the human Mac-2
      binding protein. Here, we show that CyCAP is a widely expressed secreted
      glycoprotein that modulates the host response to endotoxin. Gene-targeted CyCAP
      deficient mice are more sensitive to the lethal effects of endotoxin. In response
      to endotoxin, CyCAP-deficient mice overproduced interleukin 12 and interferon
      gamma systemically and tumor necrosis factor alpha locally; these are
      proinflammatory molecules that also promote T helper 1 responses. Furthermore,
      macrophages stimulated in vitro with endotoxin in serum deficient in CyCAP
      secreted more tumor necrosis factor alpha, supporting the proposal that CyCAP
      specifically down-modulates endotoxin signaling.

PMID- 10077628
TI  - Effective treatment of autoimmune disease and progressive renal disease by mixed
      bone-marrow transplantation that establishes a stable mixed chimerism in BXSB
      recipient mice.
AB  - Male BXSB mice spontaneously develop autoimmune disease with features similar to
      systemic lupus erythematosus. To determine whether this autoimmune disease can be
      treated as well as prevented by bone-marrow transplantation (BMT) and, at the
      same time, whether the immunity functions of lethally irradiated recipients can
      be reconstituted fully, male BXSB mice were engrafted with mixed T cell-depleted
      marrow (TCDM) both from fully allogeneic autoimmune-resistant BALB/c mice and
      from syngeneic autoimmune-prone BXSB mice, after the onset of autoimmune disease
      in the recipient mice. BMT with mixed TCDM from both resistant and susceptible
      strains of mice (mixed BMT) established stable mixed chimerism, prolonged the
      median life span, and arrested development of glomerulonephritis in BXSB mice.
      BMT with mixed TCDM also reduced the formation of anti-DNA antibodies that are
      observed typically in male mice of this strain. Furthermore, mixed BMT
      reconstituted the primary antibody production in BXSB recipients impressively.
      These findings indicate that transplantation of allogeneic autoimmune-resistant
      TCDM plus syngeneic autoimmune-prone TCDM into lethally irradiated BXSB mice can
      be used to treat autoimmune and renal disease in this strain of mice. In
      addition, this dual bone-marrow transplantation reconstitutes the immunity
      functions and avoids the immunodeficiencies that occur regularly in fully
      allogeneic chimeras after total body irradiation. This report describes an
      effective treatment of progressive renal disease and autoimmunity by establishing
      a stable mixed chimerism of TCDM transplantation from allogeneic autoimmune
      resistant BALB/c mice plus syngeneic autoimmune-prone BXSB mice into BXSB mice.

PMID- 10077629
TI  - Lymphocyte function-associated antigen-1 binding residues in intercellular
      adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM
      subfamily.
AB  - The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed
      significant differences in the presentation of the critical acidic residue
      important for integrin binding between I and non-I-domain integrin ligands. Based
      on this crystal structure, we mutagenized ICAM-2 to localize the binding site for
      the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin
      binding site runs diagonally across the GFC beta-sheet and includes residues on
      the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge
      on the upper half of domain 1, which is proposed to dock to a groove in the I
      domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I
      domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the
      recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites.
      By contrast, major differences are seen with vascular cell adhesion molecule-1
      (VCAM-1), which binds alpha4 integrins that lack an I domain. The binding site on
      VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2,
      whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1.

PMID- 10077630
TI  - Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T
      cells.
AB  - The type of cytokines produced during T cell responses determines susceptibility
      or resistance to many pathogens and influences the development of autoimmunity
      and allergy. To define the role of individual accessory molecules in cytokine
      production during primary immune responses, Drosophila cell lines expressing
      murine major histocompatibility complex class II molecules with defined
      combinations of accessory molecules were used to present peptide antigen to naive
      T cell receptor transgenic T cells. Significantly, expression of B7.1 or B7.2
      without additional accessory molecules led to very high production of interleukin
      (IL)-4, which contrasted with minimal IL-4 production elicited by conventional
      antigen presenting cells (APC). However, coexpression of ICAM-1 and B7 on
      Drosophila APC induced little IL-4, suggesting an inhibitory role for
      intercellular adhesion molecule-1 (ICAM-1). In support of this idea, stimulation
      of T cell receptor transgenic T cells with peptide presented by splenic APC
      devoid of ICAM-1 (from ICAM-1-deficient mice) led to high IL-4 production. Thus,
      the level of IL-4 production by naive CD4(+) T cells during typical primary
      responses appears to be controlled, at least in part, by T-APC interactions
      involving ICAM-1.

PMID- 10077631
TI  - In vitro comparison of the antigen-binding and stability properties of the
      various molecular forms of IgA antibodies assembled and produced in CHO cells.
AB  - The hallmark of a mucosal immune response is the production of antigen-specific
      secretory IgA (S-IgA) antibodies in external secretions. S-IgA consists of ten
      polypeptides produced in two different cell lineages. The heavy and light chains
      in plasma cells assemble into IgA, which on association with J chain become
      polymerized, whereas secretory component (SC) is added during transport across
      the epithelium. Recombinant chimeric mouse-human monomeric, dimeric, and S-IgA
      antibodies have been produced in a single CHO cell sequentially transfected with
      expression vectors carrying three independent selective markers for chimeric
      heavy and light chains, human J chain, and human SC, respectively. Biochemical
      characterization of the various molecular forms indicates that the assembly of
      the various polypeptides resulted in species of the expected size and covalence.
      All chimeric IgA antibodies retained the antigen-binding capacity of the parent
      mouse IgA antibody. The resistance of S-IgA to protease-rich intestinal washes
      was enhanced when compared with dimeric IgA lacking associated SC. Up to 20
      micrograms of recombinant S-IgA per 1 x 10(6) cells were recovered in 24 h with
      the best producing clones. We conclude that CHO cells programmed de novo with
      four different genetic elements can assemble functional chimeric S-IgA.

PMID- 10077632
TI  - The Rho-family GTP exchange factor Vav is a critical transducer of T cell
      receptor signals to the calcium, ERK, and NF-kappaB pathways.
AB  - Vav is a GTP/GDP exchange factor (GEF) for members of the Rho-family of GTPases
      that is rapidly tyrosine-phosphorylated after engagement of the T cell receptor
      (TCR), suggesting that it may transduce signals from the receptor. T cells from
      mice made Vav-deficient by gene targeting (Vav-/-) fail to proliferate in
      response to TCR stimulation because they fail to secrete IL-2. We now show that
      this is due at least in part to the failure to initiate IL-2 gene transcription.
      Furthermore, we analyze TCR-proximal signaling pathways in Vav-/- T cells and
      show that despite normal activation of the Lck and ZAP-70 tyrosine kinases, the
      mutant cells have specific defects in TCR-induced intracellular calcium fluxes,
      in the activation of extracellular signal-regulated mitogen-activated protein
      kinases and in the activation of the NF-kappaB transcription factor. Finally, we
      show that the greatly reduced TCR-induced calcium flux of Vav-deficient T cells
      is an important cause of their proliferative defect, because restoration of the
      calcium flux with a calcium ionophore reverses the phenotype.

PMID- 10077633
TI  - Novel mechanisms control the folding and assembly of lambda5/14.1 and VpreB to
      produce an intact surrogate light chain.
AB  - Surrogate light chain, which escorts the mu heavy chain to the cell surface, is a
      critical component of the pre-B cell receptor complex. The two proteins that
      comprise the surrogate light chain, VpreB and lambda5/14.1, contain both unique
      regions and Ig-like domains. The unique regions have been postulated to function
      in the assembly of the surrogate light chain. However, by using transient
      transfection of COS7 cells, we show that deletion of the unique regions of both
      proteins did not inhibit the assembly of surrogate light chain. Instead, in vivo
      folding studies showed that the unique region of lambda5/14.1 acts as an
      intramolecular chaperone by preventing the folding of this protein when it is
      expressed in the absence of its partner, VpreB. The Ig domains of both
      lambda5/14.1 and VpreB are atypical. The one in VpreB lacks one of the canonical
      beta strands whereas the one in lambda5/14.1 has an extra beta strand. Deletion
      of the extra beta strand in lambda5/14.1 completely abrogated the formation of
      the surrogate light chain, demonstrating that complementation of the incomplete
      Ig domain in VpreB by the extra beta strand in lambda5/14.1 was necessary and
      sufficient for the folding and assembly of these proteins. Our studies reveal two
      novel mechanisms for regulating surrogate light chain formation: (i) the presence
      of an intramolecular chaperone that prevents folding of the unassembled subunit
      but that remains part of the mature assembled protein, and (ii) splitting an Ig
      domain between two proteins to control their folding and assembly.

PMID- 10077634
TI  - An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich
      instability element: role in tumor cell glycolysis and the Warburg effect.
AB  - Cancer cells maintain a high glycolytic rate even in the presence of oxygen, a
      phenomenon first described over 70 years ago and known historically as the
      Warburg effect. Fructose 2,6-bisphosphate is a powerful allosteric regulator of
      glycolysis that acts to stimulate the activity of 6-phosphofructo-1-kinase (PFK
      1), the most important control point in mammalian glycolysis. The steady state
      concentration of fructose 2,6-bisphosphate in turn depends on the activity of the
      enzyme 6-phosphofructo-2-kinase (PFK-2)/fructose-2, 6-bisphosphatase, which is
      expressed in several tissue-specific isoforms. We report herein the
      identification of a gene product for this enzyme that is induced by
      proinflammatory stimuli and which is distinguished by the presence of multiple
      copies of the AUUUA mRNA instability motif in its 3'-untranslated end. This
      inducible gene for PFK-2 is expressed constitutively in several human cancer cell
      lines and was found to be required for tumor cell growth in vitro and in vivo.
      Inhibition of inducible PFK-2 protein expression decreased the intracellular
      level of 5-phosphoribosyl-1-pyrophosphate, a product of the pentose phosphate
      pathway and an important precursor for nucleic acid biosynthesis. These studies
      identify a regulatory isoenzyme that may be essential for tumor growth and
      provide an explanation for long-standing observations concerning the apparent
      coupling of enhanced glycolysis and cell proliferation.

PMID- 10077635
TI  - Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase
      identified by phenylalanine-scanning mutagenesis of the transmembrane domain of
      the amyloid precursor protein.
AB  - Proteolytic processing of the amyloid precursor protein by beta-secretase yields
      A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase,
      yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues
      (Abeta42). Because the position of gamma-secretase cleavage is crucial for the
      pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain
      residues of A4CT outside the Abeta domain with phenylalanine, stably transfected
      the constructs in COS7 cells, and determined the effect of these mutations on the
      cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with
      wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased
      Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and
      Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for
      I45F (34-fold increase) making this construct important for the generation of
      animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was
      processed mainly to Abeta38, as determined by mass spectrometry. Our data provide
      a detailed model for the active site of gamma-secretase: gamma-secretase
      interacts with A4CT by binding to one side of the alpha-helical transmembrane
      domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the
      interaction between gamma-secretase and A4CT and, thus, alter the cleavage
      specificity of gamma-secretase.

PMID- 10077636
TI  - Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin
      induced diabetes.
AB  - Streptozotocin (STZ) selectively destroys insulin-producing beta islet cells of
      the pancreas providing a model of type I diabetes. Poly(ADP-ribose) polymerase
      (PARP) is a nuclear enzyme whose overactivation by DNA strand breaks depletes its
      substrate NAD+ and then ATP, leading to cellular death from energy depletion. We
      demonstrate DNA damage and a major activation of PARP in pancreatic islets of STZ
      treated mice. These mice display a 500% increase in blood glucose and major
      pancreatic islet damage. In mice with homozygous targeted deletion of PARP (PARP 
      /-), blood glucose and pancreatic islet structure are normal, indicating
      virtually total protection from STZ diabetes. Partial protection occurs in PARP
      +/- animals. Thus, PARP activation may participate in the pathophysiology of type
      I diabetes, for which PARP inhibitors might afford therapeutic benefit.

PMID- 10077637
TI  - A model for studying megakaryocyte development and biology.
AB  - The limited current understanding of megakaryocyte-lineage development and
      megakaryocyte biology is in large part because of a paucity of useful systems in
      which to conduct experiments. To overcome this problem, we have developed a
      transgenic mouse that uses the GP-Ibalpha regulatory sequences to achieve
      megakaryocyte-lineage restricted expression of an avian retroviral receptor.
      Through the transgenic avian receptor, avian retroviruses can efficiently and
      selectively infect megakaryocyte-lineage cells in vitro and in vivo. Serial
      infections can be performed to introduce and express multiple genes in the same
      cell. We have used this system to generate and characterize a pure population of
      primary CD41-positive megakaryocyte progenitors.

PMID- 10077638
TI  - Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds
      to VEGFR2 and neuropilin-1.
AB  - Orf virus, a member of the poxvirus family, produces a pustular dermatitis in
      sheep, goats, and humans. The lesions induced after infection with orf virus show
      extensive proliferation of vascular endothelial cells, dilation of blood vessels
      and dermal swelling. An explanation for the nature of these lesions may lie in
      the discovery that orf virus encodes an apparent homolog of the mammalian
      vascular endothelial growth factor (VEGF) family of molecules. These molecules
      mediate endothelial cell proliferation, vascular permeability, angiogenesis, and
      lymphangiogenesis via the endothelial cell receptors VEGFR-1 (Flt1), VEGFR-2
      (KDR/Flk1), and VEGFR-3 (Flt4). The VEGF-like protein of orf virus strain NZ2
      (ORFV2-VEGF) is most closely related in primary structure to VEGF. In this study
      we examined the biological activities and receptor specificity of the ORFV2-VEGF
      protein. ORFV2-VEGF was found to be a disulfide-linked homodimer with a subunit
      of approximately 25 kDa. ORFV2-VEGF showed mitogenic activity on bovine aortic
      and human microvascular endothelial cells and induced vascular permeability.
      ORFV2-VEGF was found to bind and induce autophosphorylation of VEGFR-2 and was
      unable to bind or activate VEGFR-1 and VEGFR-3, but bound the newly identified
      VEGF165 receptor neuropilin-1. These results indicate that, from a functional
      viewpoint, ORFV2-VEGF is indeed a member of the VEGF family of molecules, but is
      unique, however, in that it utilizes only VEGFR-2 and neuropilin-1.

PMID- 10077639
TI  - Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated
      degradation of p53.
AB  - The Hdm2 oncoprotein inhibits p53 functions by two means: (i) it blocks p53's
      transactivation activity and (ii) it targets p53 for degradation in a proteasome
      dependent manner. Recent data indicate that Hdm2 shuttles between the nucleus and
      the cytoplasm and that the regulation of p53 levels by Hdm2 requires its nuclear
      export activity. Two different models are consistent with these observations. In
      the first, Hdm2 binds to p53 in the nucleus and shuttles p53 from the nucleus to
      the cytoplasm, and then it targets p53 to the cytoplasmic proteasome.
      Alternatively, Hdm2 and p53 could be exported separately from the nucleus and
      then associate in the cytoplasm, where Hdm2 promotes the degradation of p53. To
      distinguish between these two models, several Hdm2 mutants were employed. Hdm2NLS
      lacks the ability to enter the nucleus, whereas Hdm2NES is deficient in nuclear
      export. Hdm2NLS, Hdm2NES, or the combination of both mutants were unable to
      promote p53 degradation in the cotransfected 2KO cells (which were null for both
      the p53 and mdm2 genes), although wild-type Hdm2 efficiently reduced p53 levels
      under the same conditions. This observation is not a result of the differences in
      expression levels or stability between Hdm2 and these mutants. Moreover,
      coexpression of these mutants had no effect on wild-type Hdm-2-induced p53
      destabilization. Thus, Hdm2 must shuttle p53 from the nucleus to the cytoplasm to
      target it for degradation in the cytoplasm.

PMID- 10077640
TI  - Epidermal growth factor system regulates mucin production in airways.
AB  - Goblet-cell hyperplasia is a critical pathological feature in hypersecretory
      diseases of airways. However, the underlying mechanisms are unknown, and no
      effective therapy exists. Here we show that stimulation of epidermal growth
      factor receptors (EGF-R) by its ligands, EGF and transforming growth factor alpha
      (TGFalpha), causes MUC5AC expression in airway epithelial cells both in in vitro
      and in vivo. We found that a MUC5AC-inducing epithelial cell line, NCI-H292,
      expresses EGF-R constitutively; EGF-R gene expression was stimulated further by
      tumor necrosis factor alpha (TNFalpha). EGF-R ligands increased the expression of
      MUC5AC at both gene and protein levels, and this effect was potentiated by
      TNFalpha. Selective EGF-R tyrosine kinase inhibitors blocked MUC5AC expression
      induced by EGF-R ligands. Pathogen-free rats expressed little EGF-R protein in
      airway epithelial cells; intratracheal instillation of TNFalpha induced EGF-R in
      airway epithelial cells, and subsequent instillation of EGF-R ligands increased
      the number of goblet cells, Alcian blue-periodic acid-Schiff staining (reflecting
      mucous glycoconjugates), and MUC5AC gene expression, whereas TNFalpha, EGF, or
      TGFalpha alone was without effect. In sensitized rats, three intratracheal
      instillations of ovalbumin resulted in EGF-R expression and goblet-cell
      production in airway epithelium. Pretreatment with EGF-R tyrosine kinase
      inhibitor, BIBX1522, prevented goblet-cell production both in rats stimulated by
      TNFalpha-EGF-R ligands and in an asthma model. These findings suggest potential
      roles for inhibitors of the EGF-R cascade in hypersecretory diseases of airways.

PMID- 10077641
TI  - Transforming growth factor beta stimulation of colorectal cancer cell lines: type
      II receptor bypass and changes in adhesion molecule expression.
AB  - The type II transforming growth factor (TGF)-beta receptor gene (TGFBR2) is often
      mutated in nucleotide repeat sequences in colorectal cancers that are replication
      error positive (RER+). These mutations are thought to be selected for escape from
      growth inhibition by TGF-beta rather than representing bystander events because
      of an increased mutation rate. We investigated the role of TGFBR2 mutations in 12
      colorectal cancer cell lines. Six of these were RER+, and these were shown to
      have homozygous TGFBR2 mutations. All cell lines then were tested for changes in
      proliferation in response to TGF-beta stimulation. Despite homozygous mutation of
      the type II TGF-beta receptor, two RER+ cell lines, Lovo and SW48, showed
      statistically significant growth inhibition when stimulated by TGF-beta1 in serum
      free conditions. This shows that the type II TGF-beta receptor can be bypassed in
      certain cases to maintain growth inhibition. We next investigated whether there
      was any alternative mode through which TGFBR2 mutation may give a selective
      advantage, such as a change in adhesion molecule expression. All cell lines were
      stimulated with TGF-beta1 and adhesion molecules detected by ELISA. No consistent
      changes were identified between the RER+ and the RER- cell lines, although
      changes in E-cadherin, beta-catenin, and gamma-catenin were identified in
      individual cell lines. We conclude that (i) type II TGF-beta receptor activity
      can be bypassed and thus TGFBR2 mutations in RER+ cancers may, at least
      sometimes, be just "bystander" events and (ii) TGF-beta can affect adhesion
      molecule expression so that TGFBR2 mutation may give rise to a selective
      advantage through an effect other escape from growth inhibition.

PMID- 10077642
TI  - Cooperative action of germ-line mutations in decorin and p53 accelerates lymphoma
      tumorigenesis.
AB  - Ectopic expression of decorin in a wide variety of transformed cells results in
      growth arrest and the inability to generate tumors in nude mice. This process is
      caused by a decorin-mediated activation of the epidermal growth factor receptor,
      which leads to a sustained induction of endogenous p21(WAF1/CIP1) (the cyclin
      dependent kinase inhibitor p21) and growth arrest. However, mice harboring a
      targeted disruption of the decorin gene do not develop spontaneous tumors. To
      test the role of decorin in tumorigenesis, we generated mice lacking both decorin
      and p53, an established tumor-suppressor gene. Mice lacking both genes showed a
      faster rate of tumor development and succumbed almost uniformly to thymic
      lymphomas within 6 months [mean survival age (T50) approximately 4 months]. Mice
      harboring one decorin allele and no p53 gene developed the same spectrum of
      tumors as the double knockout animals, but had a survival rate similar to the p53
      null animals (T50 approximately 6 months). Ectopic expression of decorin in
      thymic lymphoma cells isolated from double mutant animals markedly suppressed
      their colony-forming ability. When these lymphoma cells were cocultured with
      fibroblasts derived from either wild-type or decorin null embryos, the cells grew
      faster in the absence of decorin. Moreover, exogenous decorin proteoglycan or its
      protein core significantly retarded their growth in vitro. These results indicate
      that the lack of decorin is permissive for lymphoma tumorigenesis in a mouse
      model predisposed to cancer and suggest that germ-line mutations in decorin and
      p53 may cooperate in the transformation of lymphocytes and ultimately lead to a
      more aggressive phenotype by shortening the tumor latency.

PMID- 10077643
TI  - Inhibition of growth, production of insulin-like growth factor-II (IGF-II), and
      expression of IGF-II mRNA of human cancer cell lines by antagonistic analogs of
      growth hormone-releasing hormone in vitro.
AB  - Antagonistic analogs of growth hormone-releasing hormone (GHRH) suppress growth
      of various tumors in vivo. This effect is exerted in part through inhibition of
      the GHRH-GH-insulin-like growth factor (IGF)-I axis. Nevertheless, because
      autocrine/paracrine control of proliferation by IGF-II also is a major factor in
      many tumors, the interference with this growth-stimulating pathway would offer
      another approach to tumor control. We thus investigated whether GHRH antagonists
      MZ-4-71 and MZ-5-156 also act on the tumor cells directly by blocking the
      production of IGF-II. An increase in the IGF-II concentration in the media during
      culture was found in 13 of 26 human cancer cell lines tested. Reverse
      transcription-PCR studies on 8 of these cell lines showed that they also
      expressed IGF-II mRNA. Antagonists of GHRH significantly inhibited the rate of
      proliferation of mammary (MDA-MB-468 and ZR-75-1), prostatic (PC-3 and DU-145),
      and pancreatic (MiaPaCa-2, SW-1990, and Capan-2) cancer cell lines as shown by
      colorimetric and [3H]thymidine incorporation tests and reduced the expression of
      IGF-II mRNA in the cells and the concentration of IGF-II secreted into the
      culture medium. Growth and IGF-II production of lung (H-23 and H-69) and ovarian
      (OV-1063) cancer cells that express mRNA for IGF-II and excrete large quantities
      of IGF-II also was marginally suppressed by the antagonists. These findings
      suggest that antagonistic analogs of GHRH can inhibit growth of certain tumors
      not only by inhibiting the GHRH-GH-IGF-I axis, but also by reducing the IGF-II
      production and by interfering with the autocrine regulatory pathway.

PMID- 10077644
TI  - Transdermal photopolymerization for minimally invasive implantation.
AB  - Photopolymerizations are widely used in medicine to create polymer networks for
      use in applications such as bone restorations and coatings for artificial
      implants. These photopolymerizations occur by directly exposing materials to
      light in "open" environments such as the oral cavity or during invasive
      procedures such as surgery. We hypothesized that light, which penetrates tissue
      including skin, could cause a photopolymerization indirectly. Liquid materials
      then could be injected s.c. and solidified by exposing the exterior surface of
      the skin to light. To test this hypothesis, the penetration of UVA and visible
      light through skin was studied. Modeling predicted the feasibility of transdermal
      polymerization with only 2 min of light exposure required to photopolymerize an
      implant underneath human skin. To establish the validity of these modeling
      studies, transdermal photopolymerization first was applied to tissue engineering
      by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs
      were injected s.c. and transdermally photopolymerized. Implants harvested at 2,
      4, and 7 weeks demonstrated collagen and proteoglycan production and histology
      with tissue structure comparable to native neocartilage. To further examine this
      phenomenon and test the applicability of transdermal photopolymerization for drug
      release devices, albumin, a model protein, was released for 1 week from
      photopolymerized hydrogels. With further study, transdermal photpolymerization
      potentially could be used to create a variety of new, minimally invasive surgical
      procedures in applications ranging from plastic and orthopedic surgery to tissue
      engineering and drug delivery.

PMID- 10077645
TI  - Exposure of cryptic epitopes on transthyretin only in amyloid and in
      amyloidogenic mutants.
AB  - The structural requirements for generation of amyloid from the plasma protein
      transthyretin (TTR) are not known, although it is assumed that TTR is partly
      misfolded in amyloid. In a search for structural determinants important for
      amyloid formation, we generated a TTR mutant with high potential to form amyloid.
      We demonstrated that the mutant represents an intermediate in a series of
      conformational changes leading to amyloid. Two monoclonal antibodies were
      generated against this mutant; each displayed affinity to ex vivo TTR and TTR
      mutants with amyloidogenic folding but not to wild-type TTR or mutants exhibiting
      the wild-type fold. Two cryptic epitopes were mapped to a domain of TTR, where
      most mutations associated with amyloidosis occur and which we propose is
      displaced at the initial phase of amyloid formation, opening up new surfaces
      necessary for autoaggregation of TTR monomers. The results provide direct
      biochemical evidence for structural changes in an amyloidogenic intermediate of
      TTR.

PMID- 10077646
TI  - Molecular cloning and characterization of prostase, an androgen-regulated serine
      protease with prostate-restricted expression.
AB  - The identification of genes with selective expression in specific organs or cell
      types provides an entry point for understanding biological processes that occur
      uniquely within a particular tissue. Using a subtraction approach designed to
      identify genes preferentially expressed in specific tissues, we have identified
      prostase, a human serine protease with prostate-restricted expression. The
      prostase cDNA encodes a putative 254-aa polypeptide with a conserved serine
      protease catalytic triad and an amino-terminal pre-propeptide sequence,
      indicating a potential secretory function. The genomic sequence comprises five
      exons and four introns and contains multiple copies of a chromosome 19q-specific
      minisatellite repeat. Northern analysis indicates that prostase mRNA is expressed
      in hormonally responsive normal and neoplastic prostate epithelial tissues, but
      not in prostate stromal constituents. Prostase shares 35% amino acid identity
      with prostate-specific antigen (PSA) and 78% identity with the porcine enamel
      matrix serine proteinase 1, an enzyme involved in enamel matrix degradation and
      with a putative role in the disruption of intercellular junctions. Radiation
      hybrid-panel mapping localized prostase to chromosome 19q13, a region containing
      several other serine proteases, including protease M, pancreatic/renal kallikrein
      hK1, and the prostate-specific kallikreins hK2 and hK3 (PSA). The sequence
      homology between prostase and other well-characterized serine proteases suggests
      several potential functional roles for the prostase protein that include the
      degradation of extracellular matrix and the activation of PSA and other
      proteases.

PMID- 10077647
TI  - In vivo proliferation and cell cycle kinetics of long-term self-renewing
      hematopoietic stem cells.
AB  - A rare set of hematopoietic stem cells (HSC) must undergo a massive expansion to
      produce mature blood cells. The phenotypic isolation of HSC from mice offers the
      opportunity to determine directly their proliferation kinetics. We analyzed the
      proliferation and cell cycle kinetics of long-term self-renewing HSC (LT-HSC) in
      normal adult mice. At any one time, approximately 5% of LT-HSC were in S/G2/M
      phases of the cell cycle and another 20% were in G1 phase. BrdUrd incorporation
      was used to determine the rate at which different cohorts of HSC entered the cell
      cycle over time. About 50% of LT-HSC incorporated BrdUrd by 6 days and >90%
      incorporated BrdUrd by 30 days. By 6 months, 99% of LT-HSC had incorporated
      BrdUrd. We calculated that approximately 8% of LT-HSC asynchronously entered the
      cell cycle per day. Nested reverse transcription-PCR analysis revealed cyclin D2
      expression in a high proportion of LT-HSC. Although approximately 75% of LT-HSC
      are quiescent in G0 at any one time, all HSC are recruited into cycle regularly
      such that 99% of LT-HSC divide on average every 57 days.

PMID- 10077648
TI  - Intravitreous transplantation of encapsulated fibroblasts secreting the human
      fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal
      College of Surgeons rats.
AB  - We developed an experimental approach with genetically engineered and
      encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of
      photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic
      fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible
      polymer AN69 for at least 90 days under in vitro and in vivo conditions because
      of their stable transfection with the gene for the 18-kDa form of the human basic
      fibroblast growth factor (hFGF-2). Furthermore, when transferred surgically into
      the vitreous cavity of 21-day-old Royal College of Surgeons rats, the
      microencapsulated hFGF-2-secreting fibroblasts provoked a local delay of
      photoreceptor cell degeneration, as seen at 45 days and 90 days after
      transplantation. This effect was limited to 2.08 mm2 (45 days) and 0.95 mm2 (90
      days) of the retinal surface. In both untreated eyes and control globes with
      encapsulated hFGF-2-deficient fibroblasts, the rescued area (of at most 0.08 mm2)
      was significantly smaller at both time points. Although, in a few ocular globes,
      surgical trauma induced a reorganization of the retinal cytoarchitecture, neither
      microcapsule rejection nor hFGF-2-mediated tumor formation were detected in any
      treated eyes. These findings indicate that encapsulated fibroblasts secreting
      hFGF-2 or perhaps other agents can be applied as potential therapeutic tools to
      treat retinal dystrophies.

PMID- 10077649
TI  - Identification of mutations in the c-mpl gene in congenital amegakaryocytic
      thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed
      in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia
      with no physical anomalies. Our previous hematological analysis indicated
      similarities between human CAMT and murine c-mpl (thrombopoietin receptor)
      deficiency. Because the c-mpl gene was considered as one of the candidate genes
      for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10
      year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a
      C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a
      single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10.
      Both mutations were predicted to result in a prematurely terminated c-Mpl
      protein, which, if translated, lacks all intracellular domains essential for
      signal transduction. Each of the mutations was segregated from the patient's
      parents. Accordingly, the patient was a compound heterozygote for two mutations
      of the c-mpl gene, each derived from one of the parents. The present study
      suggests that at least a certain type of CAMT is caused by the c-mpl mutation,
      which disrupts the function of thrombopoietin receptor.

PMID- 10077650
TI  - Enhancement of fluid filtration across tumor vessels: implication for delivery of
      macromolecules.
AB  - Cancer therapies using genes and other macromolecules might realize their full
      clinical potential if they could be delivered to tumor tissue in optimal
      quantities. Unfortunately, the compromised circulation within tumors poses a
      formidable resistance to adequate and uniform penetration of these agents.
      Previously, we have proposed elevated interstitial fluid pressure (IFP) as a
      major physiological barrier to delivery of macromolecules. Here we postulate that
      modulation of tumor microvascular pressure (MVP) and associated changes in IFP
      would enhance macromolecular delivery into a solid tumor. To test our hypothesis,
      we altered tumor MVP by either periodic injection or continuous infusion of
      angiotensin II (AII) and measured the resulting changes in IFP and uptake of
      macromolecules. We used the nicotinyl hydrazine derivative of human polyclonal
      IgG (HYNIC-IgG) as a nonspecific macromolecule and CC49 antibody as a specific
      macromolecule. We found that both chronic and periodic modulation of tumor MVP
      enhances transvascular fluid filtration, leading to a 40% increase in total
      uptake of the specific antibody within 4 hr of its administration. Conversely,
      neither continuous nor periodic infusion of AII induced any increase in uptake of
      nonspecific antibodies. Strategies to improve delivery of macromolecules and
      limitations of this approach are identified.

PMID- 10077651
TI  - Mechanism of increased iron absorption in murine model of hereditary
      hemochromatosis: increased duodenal expression of the iron transporter DMT1.
AB  - Hereditary hemochromatosis (HH) is a common autosomal recessive disorder
      characterized by tissue iron deposition secondary to excessive dietary iron
      absorption. We recently reported that HFE, the protein defective in HH, was
      physically associated with the transferrin receptor (TfR) in duodenal crypt cells
      and proposed that mutations in HFE attenuate the uptake of transferrin-bound iron
      from plasma by duodenal crypt cells, leading to up-regulation of transporters for
      dietary iron. Here, we tested the hypothesis that HFE-/- mice have increased
      duodenal expression of the divalent metal transporter (DMT1). By 4 weeks of age,
      the HFE-/- mice demonstrated iron loading when compared with HFE+/+ littermates,
      with elevated transferrin saturations (68.4% vs. 49.8%) and elevated liver iron
      concentrations (985 micrograms vs. 381 micrograms). By using Northern blot
      analyses, we quantitated duodenal expression of both classes of DMT1 transcripts:
      one containing an iron responsive element (IRE), called DMT1(IRE), and one
      containing no IRE, called DMT1(non-IRE). The positive control for DMT1 up
      regulation was a murine model of dietary iron deficiency that demonstrated
      greatly increased levels of duodenal DMT1(IRE) mRNA. HFE-/- mice also
      demonstrated an increase in duodenal DMT1(IRE) mRNA (average 7.7-fold), despite
      their elevated transferrin saturation and hepatic iron content. Duodenal
      expression of DMT1(non-IRE) was not increased, nor was hepatic expression of DMT1
      increased. These data support the model for HH in which HFE mutations lead to
      inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE)
      mRNA, up-regulation of DMT1, and increased absorption of dietary iron.

PMID- 10077652
TI  - The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease
      secreted by human fibroblasts is pregnancy-associated plasma protein-A.
AB  - Proteolytic cleavage of the six known insulin-like growth factor binding proteins
      (IGFBPs) is a powerful means of rapid structure and function modification of
      these important growth-regulatory proteins. Intact IGFBP-4 is a potent inhibitor
      of IGF action in vitro, and cleavage of IGFBP-4 has been shown to abolish its
      ability to inhibit IGF stimulatory effects in a variety of systems, suggesting
      that IGFBP-4 proteolysis acts as a positive regulator of IGF bioavailability.
      Here we report the isolation of an IGF-dependent IGFBP-4-specific protease from
      human fibroblast-conditioned media and its identification by mass spectrometry
      microsequencing as pregnancy-associated plasma protein-A (PAPP-A), a protein of
      unknown function found in high concentrations in the maternal circulation during
      pregnancy. Antibodies raised against PAPP-A both inhibited and immunodepleted
      IGFBP-4 protease activity in human fibroblast-conditioned media. Moreover, PAPP-A
      purified from pregnancy sera had IGF-dependent IGFBP-4 protease activity. PAPP-A
      mRNA was expressed by the human fibroblasts and osteoblasts, and PAPP-A protein
      was secreted into the culture medium. In conclusion, we have identified an IGF
      dependent IGFBP protease and at the same time assigned a function to PAPP-A. This
      represents an unanticipated union of two areas of research that were not linked
      in any way before this report.

PMID- 10077653
TI  - Spatial and temporal regulation of gap junction connexin43 in vascular
      endothelial cells exposed to controlled disturbed flows in vitro.
AB  - Hemodynamic regulation of the endothelial gap junction protein connexin43 (Cx43)
      was studied in a model of controlled disturbed flows in vitro. Cx43 mRNA, protein
      expression, and intercellular communication were mapped to spatial variations in
      fluid forces. Hemodynamic features of atherosclerotic lesion-prone regions of the
      vasculature (flow separation and recirculation) were created for periods of 5,
      16, and 30 h, with laminar shear stresses ranging between 0 and 13.5 dynes/cm2.
      Within 5 h, endothelial Cx43 mRNA expression was increased in all cells when
      compared with no-flow controls, with highest levels (up to 6- to 8-fold)
      expressed in regions of flow recirculation corresponding to high shear stress
      gradients. At 16 h, Cx43 mRNA expression remained elevated in regions of flow
      disturbance, whereas in areas of fully developed, undisturbed laminar flow, Cx43
      expression returned to control levels. In all flow regions, typical punctate Cx43
      immunofluorescence at cell borders was disrupted by 5 h. After 30 h of flow,
      disruption of gap junctions persisted in cells subjected to flow separation and
      recirculation, whereas regions of undisturbed flow were substantially restored to
      normal. These expression differences were reflected in sustained inhibition of
      intercellular communication (dye transfer) throughout the zone of disturbed flow
      (84.2 and 68.4% inhibition at 5 and 30 h, respectively); in contrast,
      communication was fully reestablished by 30 h in cells exposed to undisturbed
      flow. Up-regulation of Cx43 transcripts, sustained disorganization of Cx43
      protein, and impaired communication suggest that shear stress gradients in
      regions of disturbed flow regulate intercellular communication through the
      expression and function of Cx43.

PMID- 10077654
TI  - A model of human phenylalanine metabolism in normal subjects and in
      phenylketonuric patients.
AB  - The derivation of a quantitative model of phenylalanine metabolism in humans is
      described. The model is based on the kinetic properties of pure recombinant human
      phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine
      transamination and protein degradation. Calculated values for the steady-state
      concentration of blood phenylalanine, rate of clearance of phenylalanine from the
      blood after an oral load of the amino acid, and dietary tolerance of
      phenylalanine all agree well with data from normal as well as from
      phenylketonuric patients and obligate heterozygotes. These calculated values may
      help in the decision about the degree of restriction of phenylalanine intake that
      is necessary to achieve a satisfactory clinical outcome in classical patients and
      in those with milder forms of the disease.

PMID- 10077655
TI  - Induced mutant mouse lines that express lipoprotein lipase in cardiac muscle, but
      not in skeletal muscle and adipose tissue, have normal plasma triglyceride and
      high-density lipoprotein-cholesterol levels.
AB  - The tissue-specific expression of lipoprotein lipase (LPL) in adipose tissue
      (AT), skeletal muscle (SM), and cardiac muscle (CM) is rate-limiting for the
      uptake of triglyceride (TG)-derived free fatty acids and decisive in the
      regulation of energy balance and lipoprotein metabolism. To investigate the
      tissue-specific metabolic effects of LPL, three independent transgenic mouse
      lines were established that expressed a human LPL (hLPL) minigene predominantly
      in CM. Through cross-breeding with heterozygous LPL knockout mice, animals were
      generated that produced hLPL mRNA and enzyme activity in CM but lacked the enzyme
      in SM and AT because of the absence of the endogenous mouse LPL gene (L0-hLPL).
      LPL activity in CM and postheparin plasma of L0-hLPL mice was reduced by 34% and
      60%, respectively, compared with control mice. This reduced LPL expression was
      sufficient to rescue LPL knockout mice from neonatal death. L0-hLPL animals
      developed normally with regard to body weight and body-mass composition. Plasma
      TG levels in L0-hLPL animals were increased up to 10-fold during the suckling
      period but normalized after weaning and decreased in adult animals. L0-hLPL mice
      had normal plasma high-density lipoprotein (HDL)-cholesterol levels, indicating
      that LPL expression in CM alone was sufficient to allow for normal HDL
      production. The absence of LPL in SM and AT did not cause detectable
      morphological or histopathological changes in these tissues. However, the lipid
      composition in AT and SM exhibited a marked decrease in polyunsaturated fatty
      acids. From this genetic model of LPL deficiency in SM and AT, it can be
      concluded that CM-specific LPL expression is a major determinant in the
      regulation of plasma TG and HDL-cholesterol levels.

PMID- 10077656
TI  - Restriction of major surface protein 2 (MSP2) variants during tick transmission
      of the ehrlichia Anaplasma marginale.
AB  - Anaplasma marginale is an ehrlichial pathogen of cattle that establishes lifelong
      persistent infection. Persistence is characterized by rickettsemic cycles in
      which new A. marginale variant types, defined by the sequence of the expressed
      msp2 transcripts, emerge. The polymorphic msp2 transcripts encode structurally
      distinct MSP2 proteins and result in an antigenically diverse and continually
      changing A. marginale population within the blood. In this manuscript, we used
      sequence analysis of msp2 transcripts to show that a restricted repertoire of
      variant types, designated SGV1 and SGV2, is expressed within the tick salivary
      gland. The same SGV1 and SGV2 variant types were expressed in ticks regardless of
      the variant types expressed in the blood of infected cattle at the time of
      acquisition feeding by the ticks. Importantly, subsequent tick transmission to
      susceptible cattle resulted in acute rickettsemia composed of organisms
      expressing only the same SGV1 and SGV2 variant types. This indicates that the
      msp2 expressed by organisms within the tick salivary gland predicts the variant
      type responsible for acute rickettsemia and disease. This restriction of
      transmitted A. marginale variant types, in contrast to the marked diversity
      within persistently infected cattle, supports development of MSP2 vaccines to
      prevent acute rickettsemia in tick-transmitted infections.

PMID- 10077657
TI  - Molecular and biophysical characterization of TT virus: evidence for a new virus
      family infecting humans.
AB  - The recent isolation of a novel DNA virus from the serum of a Japanese patient
      (T.T.) has provided the latest possible candidate virus associated with
      cryptogenic hepatitis. In the present study, we report the complete nucleotide
      sequence of this virus (TTV) isolated from the serum of a West African. Based on
      PCR studies designed to amplify overlapping regions of the viral genome and
      sensitivity to digestion with mung bean nuclease, the viral genome is circular
      and negative stranded, and comprises 3,852 nt, which is 113 nt longer than the
      prototype isolate from Japan. Cesium chloride density gradient centrifugation
      demonstrated banding of the virus at 1.31-1.34 g/ml; filtration studies indicated
      that TTV had a particle size of 30-50 nm. These results suggest that the virus is
      similar to the Circoviridae, viruses known to infect plants and vertebrates (e.
      g., birds and swine); however, sequence similarity searches of available
      databases did not reveal identity between TTV and other viruses. Phylogenetic
      analyses of a 260-nt region from 151 globally distributed isolates demonstrated
      the existence of three major TTV genotypes. Several individuals at high risk for
      infection with parenterally transmitted viruses were infected with more than one
      genotype. There was no correlation between genotype and geographic origin.
      Finally, intravenous inoculation of TTV-positive human serum into chimpanzees
      demonstrated that TTV can be transmitted to primates; no biochemical or
      histological evidence for hepatitis was obtained. The distinct biophysical and
      molecular characteristics of TTV suggest that it is a member of a new family of
      viruses, which we have tentatively named the Circinoviridae.

PMID- 10077658
TI  - Effects of changes in membrane sodium flux on virulence gene expression in Vibrio
      cholerae.
AB  - The expression of several virulence factors of Vibrio cholerae is coordinately
      regulated by the ToxT molecule and the membrane proteins TcpP/H and ToxR/S, which
      are required for toxT transcription. To identify proteins that negatively affect
      toxT transcription, we screened transposon mutants of V. cholerae carrying a
      chromosomally integrated toxT::lacZ reporter construct for darker blue colonies
      on media containing 5-bromo-4-chlor-3-indolyl beta-D galactoside (X-gal). Two
      mutants had transposon insertions in a region homologous to the nqr gene cluster
      of Vibrio alginolyticus, encoding a sodium-translocating NADH-ubiquinone
      oxidoreductase (NQR). In V. alginolyticus, NQR is a respiration-linked Na+
      extrusion pump generating a sodium motive force that can be used for solute
      import, ATP synthesis, and flagella rotation. Inhibition of NQR enzyme function
      in V. cholerae by the specific inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide
      (HQNO) resulted in elevated toxT::lacZ activity. Increased toxT::lacZ expression
      in an nqr mutant strain compared with the parental strain was observed when the
      TcpP/H molecules alone were strongly expressed, suggesting that the negative
      effect of the NQR complex on toxT transcription is mediated through TcpP/H.
      However, the ability of the TcpP/H proteins to activate the toxT::lacZ reporter
      construct was greatly diminished in the presence of high NaCl concentrations in
      the growth medium. The flagellar motor of V. cholerae appears to be driven by a
      sodium motive force, and modulation of flagella rotation by inhibitory drugs,
      high media viscosity, or specific mutations resulted in increases of toxT::lacZ
      expression. Thus, the regulation of the main virulence factors of V. cholerae
      appears to be modulated by endogenous and exogenous sodium levels in a complex
      way.

PMID- 10077659
TI  - The role of an alternative sigma factor in motility and pilus formation in the
      cyanobacterium Synechocystis sp. strain PCC6803.
AB  - Disruption of a gene for an alternative sigma factor, designated sigF, in the
      freshwater, unicellular cyanobacterium Synechocystis sp. strain PCC6803 resulted
      in a pleiotropic phenotype. Most notably, this mutant lost phototactic movement
      with a concomitant loss of pili, which are abundant on the surface of wild-type
      cells. The sigF mutant also secreted both high levels of yellow-brown and UV
      absorbing pigments and a polypeptide that is similar to a large family of
      extracellular proteins that includes the hemolysins. Furthermore, the sigF mutant
      had a dramatically reduced level of the transcript from two tandemly arranged
      pilA genes (sll1694 and sll1695), which encode major structural components of
      type IV pili. Inactivation of these pilA genes eliminated phototactic movement,
      though some pili were still present in this strain. Together, these results
      demonstrate that SigF plays a critical role in motility via the control of pili
      formation and is also likely to regulate other features of the cell surface.
      Furthermore, the data provide evidence that type IV pili are required for
      phototactic movement in certain cyanobacteria and suggest that different
      populations of pili present on the Synechocystis cell surface may perform
      different functions.

PMID- 10077660
TI  - A genetic approach to trace neural circuits.
AB  - Mammalian nervous system function involves billions of neurons which are
      interconnected in a multitude of neural circuits. Here we describe a genetic
      approach to chart neural circuits. By using an olfactory-specific promoter, we
      selectively expressed barley lectin in sensory neurons in the olfactory
      epithelium and vomeronasal organ of transgenic mice. The lectin was transported
      through the axons of those neurons to the olfactory bulb, transferred to the bulb
      neurons with which they synapse, and transported through the axons of bulb
      neurons to the olfactory cortex. The lectin also was retrogradely transported
      from the bulb to neuromodulatory brain areas. No evidence could be obtained for
      adverse effects of the lectin on odorant receptor gene expression, sensory axon
      targeting in the bulb, or the generation or transmission of signals by olfactory
      sensory neurons. Transneuronal transfer was detected prenatally in the odor
      sensing pathway, but only postnatally in the pheromone-sensing pathway,
      suggesting that odors, but not pheromones, may be sensed in utero. Our studies
      demonstrate that a plant lectin can serve as a transneuronal tracer when its
      expression is genetically targeted to a subset of neurons. This technology can
      potentially be applied to a variety of vertebrate and invertebrate neural systems
      and may be particularly valuable for mapping connections formed by small subsets
      of neurons and for studying the development of connectivity as it occurs in
      utero.

PMID- 10077661
TI  - Functional repair of motor endplates after botulinum neurotoxin type A poisoning:
      biphasic switch of synaptic activity between nerve sprouts and their parent
      terminals.
AB  - Blockade of acetylcholine release by botulinum neurotoxin type A at the
      neuromuscular junction induces the formation of an extensive network of nerve
      terminal sprouts. By repeated in vivo imaging of N-(3-triethyl ammonium propyl)-4
      (4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve
      endings of the mouse sternomastoid muscle after a single intramuscular injection
      of the toxin, inhibition of stimulated uptake of the dye at the terminals was
      detected within a few days, together with an increase in staining of the newly
      formed sprouts. After 28 days, when nerve stimulation again elicited muscle
      contraction, regulated vesicle recycling occurred only in the sprouts [shown to
      contain certain soluble N-ethylmaleimide-sensitive factor attachment proteins
      (SNAREs) and to abut acetylcholine receptors] and not at the parent terminals.
      Therefore, only these sprouts could be responsible for nerve-muscle transmission
      at this time. However, a second, distinct phase of the rehabilitation process
      followed with a return of vesicle turnover to the original terminals, accompanied
      by an elimination of the by then superfluous sprouts. This extension and later
      removal of "functional" sprouts indicate their fundamental importance in the
      repair of paralyzed endplates, a finding with ramifications for the vital process
      of nerve regeneration.

PMID- 10077662
TI  - Stimulus-secretion coupling in neurohypophysial nerve endings: a role for
      intravesicular sodium?
AB  - It is generally accepted that Ca is essentially involved in regulated secretion,
      but the role of this cation, as well as others such as Na, is not well
      understood. An illustrative example occurs in neurohypophysial secretion, where
      an experimentally induced increase in the cytosolic concentration of Na+ can
      induce continuous neuropeptide release. In contrast, an increase in cytosolic
      Ca2+ will have only a transient stimulatory effect. The secretion-promoting
      targets for Ca2+ are not known; they may be cytosolic, as is usually assumed, but
      they may also be intravesicular, especially in view of evidence that Ca-rich
      secretory vesicles are preferentially secreted. In the present work, we have
      investigated the movements of these cations into and out of secretory vesicles
      during stimulus-secretion coupling. Isolated rat neurohypophysial nerve endings
      were stimulated by potassium (55 mM) depolarization, and at 6 min (peak
      secretion) and 20 min after the onset of stimulation, the elemental content of
      individual secretory vesicles was measured by quantitative x-ray microanalysis. A
      depolarization-induced transient increase in intravesicular Na+ concentration was
      found to coincide with the onset of secretion. Moreover, only a predicted small
      fraction of peripheral vesicles-presumably the docked ones-were Na+-loaded. The
      low sulfur concentration of Na+-rich vesicles most likely resulted from vesicle
      swelling. The results suggest that high intravesicular Na+ concentrations in
      docked vesicles, occurring by Na+/Ca2+ exchange or by transient fusion pore
      opening, is a proximal event in exocytosis.

PMID- 10077663
TI  - Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes
      virus.
AB  - To test the utility of gene therapeutic approaches for the treatment of pain, a
      recombinant herpes simplex virus, type 1, has been engineered to contain the cDNA
      for an opioid peptide precursor, human preproenkephalin, under control of the
      human cytomegalovirus promoter. This virus and a similar recombinant containing
      the Escherichia coli lacZ gene were applied to the abraded skin of the dorsal
      hindpaw of mice. After infection, the presence of beta-galactosidase in neuronal
      cell bodies of the relevant spinal ganglia (lacZ-containing virus) and of human
      proenkephalin (preproenkephalin-encoding virus) in the central terminals of these
      neurons indicated appropriate gene delivery and expression. Baseline foot
      withdrawal responses to noxious radiant heat mediated by Adelta and C fibers were
      similar in animals infected with proenkephalin-encoding and beta-galactosidase
      encoding viruses. Sensitization of the foot withdrawal response after application
      of capsaicin (C fibers) or dimethyl sulfoxide (Adelta fibers) observed in control
      animals was reduced or eliminated in animals infected with the proenkephalin
      encoding virus for at least 7 weeks postinfection. Hence, preproenkephalin cDNA
      delivery selectively blocked hyperalgesia without disrupting baseline sensory
      neurotransmission. This blockade of sensitization was reversed by administration
      of the opioid antagonist naloxone, apparently acting in the spinal cord. The
      results demonstrate that the function of sensory neurons can be selectively
      altered by viral delivery of a transgene. Because hyperalgesic mechanisms may be
      important in establishing and maintaining neuropathic and other chronic pain
      states, this approach may be useful for treatment of chronic pain and
      hyperalgesia in humans.

PMID- 10077664
TI  - Cortical bitufted, horizontal, and Martinotti cells preferentially express and
      secrete reelin into perineuronal nets, nonsynaptically modulating gene
      expression.
AB  - Reelin (Reln) is a protein with some structural analogies with other
      extracellular matrix proteins that functions in the regulation of neuronal
      migration during the development of cortical laminated structures. In the cortex
      of adult animals, Reln is expressed primarily in gamma-aminobutyric acid
      (GABA)ergic neurons and is secreted into perineuronal nets. However, only 50-60%
      of GABAergic interneurons express Reln. We have characterized this subpopulation
      of cortical GABAergic neurons that expresses Reln by using two strategies: (i) a
      double immunolabeling procedure to determine the colocalization of Reln with
      neuropeptides and Ca2+-binding proteins and (ii) a combination of Golgi staining
      and Reln immunolabeling to determine the morphology of the rat cortical cells
      that store Reln. Many interneurons that express Neuropeptide Y (NPY) or
      somatostatin (but none of those that express parvalbumin) are Reln
      immunopositive. A small population of calbindin-positive interneurons and very
      few calretinin-positive cells express Reln immunopositivity. Golgi staining
      revealed that layer I horizontal cells, layer II-V bitufted neurons, and some
      deep cortical layer Martinotti cells express Reln. Basket and chandelier cells
      are often immunopositive to parvalbumin, but never to Reln. Although Reln is
      secreted by GABAergic neurons, its target are not the GABA receptors, but rather
      may be extrasynaptically located in perineuronal nets and concerned with the
      modulation of neuronal plasticity. Dab1, the target adapter protein that
      presumably mediates transcription regulation via the extrasynaptic actions of
      Reln, is expressed predominantly in pyramidal neurons, but it can also be
      detected in a small population of GABAergic neurons that are neither horizontal
      nor bitufted neurons.

PMID- 10077665
TI  - Induction of utrophin gene expression by heregulin in skeletal muscle cells: role
      of the N-box motif and GA binding protein.
AB  - The modulation of utrophin gene expression in muscle by the nerve-derived factor
      agrin plausibly involves the trophic factor ARIA/heregulin. Here we show that
      heregulin treatment of mouse and human cultured myotubes caused a approximately
      2.5-fold increase in utrophin mRNA levels. Transient transfection experiments
      with utrophin promoter-reporter gene constructs showed that this increase
      resulted from an enhanced transcription of the utrophin gene. In the case of the
      nicotinic acetylcholine receptor delta and epsilon subunit genes, heregulin was
      previously reported to stimulate transcription via a conserved promoter element,
      the N-box, which binds the multimeric Ets-related transcription factor GA binding
      protein (GABP). Accordingly, site-directed mutagenesis of a single N-box motif in
      the utrophin gene promoter abolished the transcriptional response to heregulin.
      In addition, overexpression of heregulin, or of the two GABP subunits in cultured
      myotubes, caused an N-box-dependent increase of the utrophin promoter activity.
      In vivo, direct gene transfer into muscle confirmed that heregulin regulates
      utrophin gene expression. Finally, electrophoretic mobility shift assays and
      supershift experiments performed with muscle extracts revealed that the N-box of
      the utrophin promoter binds GABP. These findings suggest that the subsynaptic
      activation of transcription by heregulin via the N-box motif and GABP are
      conserved among genes expressed at the neuromuscular junction. Because utrophin
      can functionally compensate for the lack of dystrophin, the elucidation of the
      molecular mechanisms regulating utrophin gene transcription may ultimately lead
      to therapies based on utrophin expression throughout the muscle fibers of
      Duchenne muscular dystrophy patients.

PMID- 10077666
TI  - Plaque-independent disruption of neural circuits in Alzheimer's disease mouse
      models.
AB  - Autosomal dominant forms of familial Alzheimer's disease (FAD) are associated
      with increased production of the amyloid beta peptide, Abeta42, which is derived
      from the amyloid protein precursor (APP). In FAD, as well as in sporadic forms of
      the illness, Abeta peptides accumulate abnormally in the brain in the form of
      amyloid plaques. Here, we show that overexpression of FAD(717V-->F)-mutant human
      APP in neurons of transgenic mice decreases the density of presynaptic terminals
      and neurons well before these mice develop amyloid plaques. Electrophysiological
      recordings from the hippocampus revealed prominent deficits in synaptic
      transmission, which also preceded amyloid deposition by several months. Although
      in young mice, functional and structural neuronal deficits were of similar
      magnitude, functional deficits became predominant with advancing age. Increased
      Abeta production in the context of decreased overall APP expression, achieved by
      addition of the Swedish FAD mutation to the APP transgene in a second line of
      mice, further increased synaptic transmission deficits in young APP mice without
      plaques. These results suggest a neurotoxic effect of Abeta that is independent
      of plaque formation.

PMID- 10077667
TI  - Modulation of glycine receptors in retinal ganglion cells by zinc.
AB  - Effects of zinc, an endogenous neuromodulator in the central nervous system, on
      glycine receptors (GlyRs) in retinal ganglion cells were investigated by using
      the whole-cell voltage-clamp technique. Zn2+ at low concentration (<2 microM)
      potentiated the glycine-induced chloride current and at higher concentration (>10
      microM) suppressed it. This biphasic regulatory action of zinc acted selectively
      on the fast component of the glycine-induced current mediated by the strychnine
      sensitive GlyRs, but not on the slow component mediated by the 5,7
      dichlorokynurenic acid-sensitive GlyRs. Dose-response studies showed that 1
      microM Zn2+ increased the maximum glycine response (I approximately) and shifted
      the EC50 to the left, suggesting that Zn2+ at low concentrations acts as an
      allosteric activator of the strychnine-sensitive GlyRs. Zn2+ at a concentration
      of 100 microM did not alter I approximately and shifted the EC50 to the right,
      indicating that Zn2+ at high concentrations acts as a competitive inhibitor of
      the GlyRs. Physiological functions of zinc modulation of GlyRs in retinal
      ganglion cells are discussed.

PMID- 10077668
TI  - Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D
      aspartate receptor.
AB  - The molecular basis of long-term potentiation (LTP), a long-lasting change in
      synaptic transmission, is of fundamental interest because of its implication in
      learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D
      aspartate (NMDA)-type glutamate receptors and subsequent activation of
      Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular
      understanding of LTP it is crucial to know how CaMKII is localized to its
      postsynaptic targets because protein kinases often are targeted to their
      substrates by adapter proteins. Here we show that CaMKII directly binds to the
      NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIalpha by
      stimulation of NMDA receptors in forebrain slices increase this association. This
      interaction places CaMKII not only proximal to a major source of Ca2+ influx but
      also close to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      type glutamate receptors, which become phosphorylated upon stimulation of NMDA
      receptors in these forebrain slices. Identification of the postsynaptic adapter
      for CaMKII fills a critical gap in the understanding of LTP because CaMKII
      mediated phosphorylation of AMPA receptors is an important step during LTP.

PMID- 10077669
TI  - Stimulated changes in localized cerebral energy consumption under anesthesia.
AB  - Focal changes in the cerebral metabolic rate of glucose utilization (CMRglc) are
      small (10-40%) during sensory activation in awake humans, as well as in awake
      rodents and primates (20-50%). They are significantly larger (50-250%) in sensory
      activation studies of anesthetized rats and cats. Our data, in agreement with
      literature values, show that in the resting anesthetized state values of CMRglc
      are lower than in the resting nonanesthetized state whereas the final state
      values, reached upon activation, are similar for the anesthetized and
      nonanesthetized animals. The lower resting anesthetized state values of CMRglc
      explain why the increments upon activation from anesthesia are larger than when
      starting from the nonanesthetized conditions. Recent 13C NMR measurements in our
      laboratory have established a quantitative relationship between the energetics of
      glucose oxidation, CMRglc (oxidative), and the flux of the glutamate/gamma
      aminobutyric acid/glutamine neurotransmitter cycle, Vcycle. In both the resting
      awake value of CMRglc(oxidative), and its increment upon stimulation, a large
      majority (approximately 80%) of the brain energy consumption is devoted to
      Vcycle. In the differencing methods of functional imaging, it is assumed that the
      incremental change in the measured signal represents the modular activity that
      supports the functional response. However, the same amount of activity must be
      present during the response to stimulation, irrespective of the initial basal
      state of the cortex. Thus, whereas the incremental signals of DeltaCMRglc can
      localize neurotransmitter activity, the magnitude of such activity during the
      response is represented by the total localized CMRglc, not the increment.

PMID- 10077670
TI  - The role of immunophilins in mutant superoxide dismutase-1linked familial
      amyotrophic lateral sclerosis.
AB  - It has been reported that expression of familial amyotrophic lateral sclerosis
      (FALS)-associated mutant Cu/Zn superoxide dismutase-1 (SOD) induces apoptosis of
      neuronal cells in culture associated with an increase in reactive oxygen species.
      SOD recently has been shown to prevent calcineurin inactivation, initiating the
      present investigations examining the role of calcineurin in mutant SOD-induced
      cell death. Wild-type or mutant SOD was expressed in neuronal cells by infection
      with replication-deficient adenoviruses. PC12 cells overexpressing human wild
      type SOD exhibited higher calcineurin activity than cells expressing FALS-related
      mutant SOD (SODV148G); however, cells expressing SODV148G had calcineurin
      activity equal to mock-infected cells, suggesting that cell death induced by
      mutant SOD was not related to a decrease in calcineurin activity. Calcineurin
      antagonists such as cyclosporin A and FK506, as well as nonimmunosuppressant
      analogs of cyclosporin A, significantly enhanced SODV148G- and SODA4V-induced
      cell death. Because both groups of drugs inhibit the rotamase activity of
      cyclophilins (CyP), but only the immunosuppressant analogs inhibit calcineurin
      activity, these data suggest that rotamase inhibition underlies the enhanced cell
      death after SODV148G expression. The importance of rotamase activity in mutant
      SOD-mediated apoptosis was supported by experiments showing that overexpressed
      wild-type cyclophilin A (CyPA), but not CyPA with a rotamase active site point
      mutation, protected cells from death after SODV148G expression. These data
      suggest that mutant SOD produces a greater need for rotamase and, also,
      highlights possible new therapeutic strategies in FALS.

PMID- 10077671
TI  - Measures of degeneracy and redundancy in biological networks.
AB  - Degeneracy, the ability of elements that are structurally different to perform
      the same function, is a prominent property of many biological systems ranging
      from genes to neural networks to evolution itself. Because structurally different
      elements may produce different outputs in different contexts, degeneracy should
      be distinguished from redundancy, which occurs when the same function is
      performed by identical elements. However, because of ambiguities in the
      distinction between structure and function and because of the lack of a
      theoretical treatment, these two notions often are conflated. By using
      information theoretical concepts, we develop here functional measures of the
      degeneracy and redundancy of a system with respect to a set of outputs. These
      measures help to distinguish the concept of degeneracy from that of redundancy
      and make it operationally useful. Through computer simulations of neural systems
      differing in connectivity, we show that degeneracy is low both for systems in
      which each element affects the output independently and for redundant systems in
      which many elements can affect the output in a similar way but do not have
      independent effects. By contrast, degeneracy is high for systems in which many
      different elements can affect the output in a similar way and at the same time
      can have independent effects. We demonstrate that networks that have been
      selected for degeneracy have high values of complexity, a measure of the average
      mutual information between the subsets of a system. These measures promise to be
      useful in characterizing and understanding the functional robustness and
      adaptability of biological networks.

PMID- 10077672
TI  - Evidence for a physical interaction between presenilin and Notch.
AB  - Genetic analyses in Caenorhabditis elegans demonstrate that sel-12 and hop-1,
      homologues of the Alzheimer's disease-associated presenilin genes, modify
      signaling through LIN-12 and GLP-1, homologues of the Notch cell surface
      receptor. To gain insight into the biochemical basis of this genetic interaction,
      we tested the possibility that presenilin-1 (PS1) physically associates with the
      Notch1 receptor in mammalian cells. Notch1 and PS1 coimmunoprecipitated from
      transiently transfected human embryonic kidney 293 cell lysates in a detergent
      sensitive manner, consistent with a noncovalent physical association between the
      two proteins. The interaction predominantly occurred early in the secretory
      pathway prior to Notch cleavage in the Golgi, because PS1 immunoprecipitation
      preferentially recovered the full-length Notch1 precursor. When PS1 was
      immunoprecipitated from 293 cells that had been metabolically labeled with
      [35S]methionine and [35S]cysteine, Notch1 was the primary protein detected in PS1
      immunoprecipitates, suggesting that this interaction is specific. Furthermore,
      endogenous Notch and presenilin coimmunoprecipitated from cultured Drosophila
      cells, indicating that physical interaction can occur at physiological expression
      levels. These results suggest that the genetic relationship between presenilins
      and the Notch signaling pathway derives from a direct physical association
      between these proteins in the secretory pathway.

PMID- 10077673
TI  - Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate type glutamate receptors.
AB  - The ability of central glutamatergic synapses to change their strength in
      response to the intensity of synaptic input, which occurs, for example, in long
      term potentiation (LTP), is thought to provide a cellular basis for memory
      formation and learning. LTP in the CA1 field of the hippocampus requires
      activation of Ca2+/calmodulin-kinase II (CaM-KII), which phosphorylates Ser-831
      in the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      glutamate receptor (AMPA-R), and this activation/phosphorylation is thought to be
      a postsynaptic mechanism in LTP. In this study, we have identified a molecular
      mechanism by which CaM-KII potentiates AMPA-Rs. Coexpression in HEK-293 cells of
      activated CaM-KII with GluR1 did not affect the glutamate affinity of the
      receptor, the kinetics of desensitization and recovery, channel rectification,
      open probability, or gating. Single-channel recordings identified multiple
      conductance states for GluR1, and coexpression with CaM-KII or a mutation of Ser
      831 to Asp increased the contribution of the higher conductance states. These
      results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by
      increasing single-channel conductance of existing functional AMPA-Rs or by
      recruiting new high-conductance-state AMPA-Rs.

PMID- 10077674
TI  - Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity
      to nonsteroid antiinflammatory drugs.
AB  - The transformed monocyte/macrophage cell line J774.2 undergoes apoptosis when
      treated for 48 h with competitive inhibitors of cyclooxygenase (COX) isoenzymes 1
      and 2. Many of these nonsteroid antiinflammatory drugs (NSAIDs), but in
      particular diclofenac, induce during this time period a COX activity that
      coincides with a robust induction of COX-2 protein. Induction of this activity
      requires high, apoptosis-inducing concentrations of diclofenac (>100 microM).
      Prolonged treatment of J774.2 cells with lower doses of diclofenac inhibits COX
      activity, indicating that diclofenac is a time-dependent, pseudoirreversible
      inhibitor of COX-2. It is difficult to wash out the inhibition. However, the
      activity evoked by high concentrations of diclofenac has a profoundly distinct
      COX active site that allows diclofenac, its inducer, to be washed readily from
      its active site. The diclofenac-induced activity also has the unusual property of
      being more sensitive to inhibition by acetaminophen (IC50 = 0.1-1.0 mM) than COX
      2 induced with bacterial lipopolysaccharide. Moreover, relative to COX-1 or COX
      2, diclofenac-induced enzyme activity shows significantly reduced sensitivity to
      inhibition by diclofenac or other competitively acting nonsteroid
      antiinflammatory drugs (NSAIDs) and the enzyme activity is insensitive to
      aspirin. If the robust induction of COX-2 observed is responsible for diclofenac
      induced COX enzyme activity, it is clear that COX-2 can, therefore, exist in two
      catalytically active states. A luciferase reporter-construct that contains part
      of the COX-2 structure and binds into the membrane showed that chronic diclofenac
      treatment of fibroblasts results in marked mobilization of the fusion protein.
      Such a mobilization could result in enzymatically distinct COX-2 populations in
      response to chronic diclofenac treatment.

PMID- 10077675
TI  - Insulin increases near-membrane but not global Ca2+ in isolated skeletal muscle.
AB  - It has long been debated whether changes in Ca2+ are involved in insulin
      stimulated glucose uptake in skeletal muscle. We have now investigated the effect
      of insulin on the global free myoplasmic Ca2+ concentration and the near-membrane
      free Ca2+ concentration ([Ca2+]mem) in intact, single skeletal muscle fibers from
      mice by using fluorescent Ca2+ indicators. Insulin has no effect on the global
      free myoplasmic Ca2+ concentration. However, insulin increases [Ca2+]mem by
      approximately 70% and the half-maximal increase in [Ca2+]mem occurs at an insulin
      concentration of 110 microunits per ml. The increase in [Ca2+]mem by insulin
      persists when sarcoplasmic reticulum Ca2+ release is inhibited but is lost by
      perfusing the fiber with a low Ca2+ medium or by addition of L-type Ca2+ channel
      inhibitors. Thus, insulin appears to stimulate Ca2+ entry into muscle cells via L
      type Ca2+ channels. Wortmannin, which inhibits insulin-mediated activation of
      glucose transport in isolated skeletal muscle, also inhibits the insulin-mediated
      increase in [Ca2+]mem. These data demonstrate a new facet of insulin signaling
      and indicate that insulin-mediated increases in [Ca2+]mem in skeletal muscle may
      underlie important actions of the hormone.

PMID- 10077676
TI  - Insulin-like growth factor 1 is required for G2 progression in the estradiol
      induced mitotic cycle.
AB  - Insulin-like growth factor 1 (IGF1) has been proposed as a "G1-progression
      factor" and as a mediator of estradiol's (E2) mitogenic effects on the uterus. To
      test these hypotheses, we compared E2's mitogenic effects on the uteri of Igf1
      targeted gene deletion (null) and wild-type littermate mice. The proportion of
      uterine cells involved in the cell cycle and G1- and S-phase kinetics were not
      significantly different in wild-type and Igf1-null mice. However, the appearance
      of E2-induced mitotic figures and cell number increases were profoundly retarded
      in Igf1-null uterine tissue. There was a significant increase in nuclear DNA
      concentration in Igf1-null cells, consistent with a G2 arrest. Interestingly,
      apoptotic cells were also significantly reduced in abundance, and the normal
      massive apoptotic response to E2 withdrawal was absent in the Igf1-null uterus.
      These data show that Igf1 is an essential mediator of E2's mitogenic effects,
      with a critical role not in G1 progression but in G2 progression.

PMID- 10077677
TI  - EDS1, an essential component of R gene-mediated disease resistance in Arabidopsis
      has homology to eukaryotic lipases.
AB  - A major class of plant disease resistance (R) genes encodes leucine-rich-repeat
      proteins that possess a nucleotide binding site and amino-terminal similarity to
      the cytoplasmic domains of the Drosophila Toll and human IL-1 receptors. In
      Arabidopsis thaliana, EDS1 is indispensable for the function of these R genes.
      The EDS1 gene was cloned by targeted transposon tagging and found to encode a
      protein that has similarity in its amino-terminal portion to the catalytic site
      of eukaryotic lipases. Thus, hydrolase activity, possibly on a lipid-based
      substrate, is anticipated to be central to EDS1 function. The predicted EDS1
      carboxyl terminus has no significant sequence homologies, although analysis of
      eight defective eds1 alleles reveals it to be essential for EDS1 function. Two
      plant defense pathways have been defined previously that depend on salicylic
      acid, a phenolic compound, or jasmonic acid, a lipid-derived molecule. We
      examined the expression of EDS1 mRNA and marker mRNAs (PR1 and PDF1.2,
      respectively) for these two pathways in wild-type and eds1 mutant plants after
      different challenges. The results suggest that EDS1 functions upstream of
      salicylic acid-dependent PR1 mRNA accumulation and is not required for jasmonic
      acid-induced PDF1.2 mRNA expression.

PMID- 10077678
TI  - Channel-mediated high-affinity K+ uptake into guard cells from Arabidopsis.
AB  - Potassium uptake by higher plants is the result of high- or low-affinity
      transport accomplished by different sets of transporters. Although K+ channels
      were thought to mediate low-affinity uptake only, the molecular mechanism of the
      high-affinity, proton-dependent K+ uptake system is still scant. Taking advantage
      of the high-current resolution of the patch-clamp technique when applied to the
      small Arabidopsis thaliana guard cells densely packed with voltage-dependent K+
      channels, we could directly record channels working in the concentration range of
      high-affinity K+ uptake systems. Here we show that the K+ channel KAT1 expressed
      in Arabidopsis guard cells and yeast is capable of mediating potassium uptake
      from media containing as little as 10 microM of external K+. Upon reduction of
      the external K+ content to the micromolar level the voltage dependence of the
      channel remained unaffected, indicating that this channel type represents a
      voltage sensor rather than a K+-sensing valve. This behavior results in K+
      release through K+ uptake channels whenever the Nernst potential is negative to
      the activation threshold of the channel. In contrast to the H+-coupled K+ symport
      shown to account for high-affinity K+ uptake in roots, pH-dependent K+ uptake
      into guard cells is a result of a shift in the voltage dependence of the K+
      channel. We conclude that plant K+ channels activated by acid pH may play an
      essential role in K+ uptake even from dilute solutions.

PMID- 10077679
TI  - Phenomenological theory of mortality evolution: its singularities, universality,
      and superuniversality.
AB  - The probability to survive to the age x universally increases with the mean
      lifespan x(bar). For species as remote as humans and flies, for a given x the
      rate of its evolution with x is constant, except for the narrow vicinity of a
      certain x(bar) = x* (which equals 75 years for humans and 32 days for flies and
      which is independent of age, population, and living conditions). At x(bar)
      approximately x* the evolution rate jumps to a different value. Its next jump is
      predicted at x(bar) approximately 87 years for humans and approximately 59 days
      for flies. Such singularities are well known in physics and mathematics as phase
      transitions. In the considered case different population "phases" have
      significantly different survival evolution rates. The evolution is rapid-life
      expectancy may double within a lifespan of a single generation. Survival
      probability depends on age x and mean longevity x(bar) only (for instance,
      survival curves of 1896 Swedes and 1947 Japanese with approximately equal x(bar)
      are very close, although they are related to different races in different
      countries at different periods in their different history.) With no adjustable
      parameters, its presented universal law quantitatively agrees with all lifetable
      data. According to this law, the impact of all factors but age reduces to the
      mean lifespan only. In advanced and old age, this law is superuniversal--it is
      approximately the same for species as remote as humans and flies. It yields
      survival probability that linearly depends on the mean lifespan x(bar). As a
      result, when human x(bar) almost doubles (from 35.5 to 69.3 years), life
      expectancy at 70 years increases from 8 to 9.5 years only. Other implications of
      the universal law are also considered.

PMID- 10077680
TI  - Declining survival probability threatens the North Atlantic right whale.
AB  - The North Atlantic northern right whale (Eubalaena glacialis) is considered the
      most endangered large whale species. Its population has recovered only slowly
      since the cessation of commercial whaling and numbers about 300 individuals. We
      applied mark-recapture statistics to a catalog of photographically identified
      individuals to obtain the first statistically rigorous estimates of survival
      probability for this population. Crude survival decreased from about 0.99 per
      year in 1980 to about 0.94 in 1994. We combined this survival trend with a
      reported decrease in reproductive rate into a branching process model to compute
      population growth rate and extinction probability. Population growth rate
      declined from about 1. 053 in 1980 to about 0.976 in 1994. Under current
      conditions the population is doomed to extinction; an upper bound on the expected
      time to extinction is 191 years. The most effective way to improve the prospects
      of the population is to reduce mortality. The right whale is at risk from
      entanglement in fishing gear and from collisions with ships. Reducing this human
      caused mortality is essential to the viability of this population.

PMID- 10077681
TI  - Spatial attention affects brain activity in human primary visual cortex.
AB  - Functional MRI was used to test whether instructing subjects to attend to one or
      another location in a visual scene would affect neural activity in human primary
      visual cortex. Stimuli were moving gratings restricted to a pair of peripheral,
      circular apertures, positioned to the right and to the left of a central fixation
      point. Subjects were trained to perform a motion discrimination task, attending
      (without moving their eyes) at any moment to one of the two stimulus apertures.
      Functional MRI responses were recorded while subjects were cued to alternate
      their attention between the two apertures. Primary visual cortex responses in
      each hemisphere modulated with the alternation of the cue; responses were greater
      when the subject attended to the stimuli in the contralateral hemifield. The
      attentional modulation of the brain activity was about 25% of that evoked by
      alternating the stimulus with a uniform field.

PMID- 10077682
TI  - X chromosome evidence for ancient human histories.
AB  - Diverse African and non-African samples of the X-linked PDHA1 (pyruvate
      dehydrogenase E1 alpha subunit) locus revealed a fixed DNA sequence difference
      between the two sample groups. The age of onset of population subdivision appears
      to be about 200 thousand years ago. This predates the earliest modern human
      fossils, suggesting the transformation to modern humans occurred in a subdivided
      population. The base of the PDHA1 gene tree is relatively ancient, with an
      estimated age of 1.86 million years, a late Pliocene time associated with early
      species of Homo. PDHA1 revealed very low variation among non-Africans, but in
      other respects the data are consistent with reports from other X-linked and
      autosomal haplotype data sets. Like these other genes, but in conflict with
      microsatellite and mitochondrial data, PDHA1 does not show evidence of human
      population expansion.

PMID- 10077683
TI  - Linguistic diversity of the Americas can be reconciled with a recent
      colonization.
AB  - The Americas harbor a very great diversity of indigenous language stocks, many
      more than are found in any other continent. J. Nichols [(1990) Language 66, 475
      521] has argued that this diversity indicates a great time depth of in situ
      evolution. She thus infers that the colonization of the Americas must have begun
      around 35,000 years ago. This estimate is much earlier than the date for which
      there is strong archaeological support, which does not much exceed 12,000 years.
      Nichols' assumption is that the diversity of linguistic stocks increases linearly
      with time. This paper compares the major continents of the world to show that
      this assumption is not correct. In fact, stock diversity is highest in the
      Americas, which are by consensus the youngest continents, intermediate in
      Australia and New Guinea, and lowest in Africa and Eurasia where the time depth
      is greatest. If anything, then, after an initial radiation, stock diversity
      decreases with time. A simple model is outlined that predicts these dynamics. It
      assumes that early in the peopling of continents, there are many unfilled niches
      for communities to live in, and so fissioning into new lineages is frequent. As
      the habitat is filled up, the rate of fissioning declines and lineage extinction
      becomes the dominant evolutionary force.

PMID- 10077696
TI  - Brain primary cultures and vibrodissociated cells as tools for the study of
      astroglial properties and functions.
AB  - The glial cells, especially the astroglia constitute a prominent part of the
      brain cell volume. Astroglial properties are difficult to study in the intact
      nervous system. For that reason, different in vitro models have been developed.
      The development of cell and tissue cultivation conditions has been the
      prerequisite to our present knowledge of the biochemistry and pharmacology of
      glial cells and to some extent even neurons. It is, however, an advantage if
      results from tissue culture can be evaluated in more in vivo like systems. We
      here describe a method for acute isolation of freshly prepared neurons and glial
      cells.

PMID- 10077697
TI  - Neurotrophin-3 increases neurite outgrowth and apoptosis in explants of the
      chicken neural plate.
AB  - This study examined the effect of neurotrophin-3 (NT-3) on neurite outgrowth and
      apoptosis of chicken neural plate explants prior to neural tube formation. In
      situ hybridization revealed that mRNA for the full-length (catalytic) NT-3
      receptor, TrkC, was present in, and limited to, the neural plate (including the
      neural folds) coincident with its formation. Neural plate explants were
      maintained in vitro on a collagen gel under serum-free conditions in the presence
      or absence of exogenous NT-3 and/or an antibody to NT-3. In the absence of
      exogenous NT-3, explants exhibited neurite outgrowth after several days in vitro;
      apoptotic cells were also seen after 2 days in vitro. This does not appear to be
      due to endogenous NT-3, since the total number of neurites or apoptotic cells was
      unchanged if explants were exposed to an NT-3 antibody for the entire culture
      period. In the presence of exogenous NT-3, neural plate explants exhibited a dose
      dependent statistically significant increase in the total number of neurites as
      compared to explants maintained under control conditions, as well as a
      statistically significant increase in apoptosis. These NT-3 effects were blocked
      by an NT-3 antibody. In contrast, NT-3 had no effect on the length of neurites.
      These findings suggest that NT-3 may play a role during early neural development
      in vivo.

PMID- 10077698
TI  - Differential expression of serotonin 5-HT2 receptors during rat embryogenesis.
AB  - Serotonin (5-HT) is a neurotransmitter that also functions as a hormone and a
      growth factor. 5-HT is involved in numerous physiological actions and displays
      complex pharmacological properties. As a growth factor, 5-HT plays a role in cell
      proliferation and differentiation of neuronal and nonneuronal tissue and it
      transduces its signals through more than fourteen subtypes of 5-HT receptors.
      Since determination of the expression and distribution is important for
      understanding the role of the 5-HT receptors, we have developed an RNase
      protection assay (RPA) that allows the simultaneous analysis of 5-HT2AR, 5-HT2BR,
      and 5-HT2CR per sample of RNA. This multiprobe set also comprises probes for two
      house-keeping genes, L32 and GAPDH, which control for sample-loading errors.
      Using this RPA probe set, we have examined the relative expression of 5-HT2AR, 5
      HT2BR, and 5-HT2CR in rat embryos inclusively from embryonic day (ED) 9 to 21 of
      development. Our data indicate that 5-HT2AR levels gradually increased from ED11
      to ED21. The expression of 5-HT2BR was decreased between ED9 to ED11 then
      remained relatively constant through ED21. 5-HT2CR was initially expressed at
      residual levels between ED9 and ED12 but dramatically increased to a peak level
      at ED13, then decreased by ED17. Expression of the 5-HT2 receptors in these
      tissues was confirmed independently by RT-PCR indicating that there is
      developmental regulation in the expression of these receptors. The 5-HT2R
      multiprobe assay will be useful for detecting relative changes in the expression
      of these receptors in developmental, normal and pathological tissues as well as
      for monitoring relative changes in expression resulting from the use of
      pharmaceutical agents.

PMID- 10077699
TI  - Folate and folate-dependent enzymes associated with rat CNS development.
AB  - Folic acid and its derivatives are important mediators in growth-related cellular
      processes. The concentration of folate and two folate-dependent enzymes, 10
      formyltetrahydrofolate synthetase (10-FTHFS) and 10-formyltetrahydrofolate
      dehydrogenase (10-FTHFDH), was determined in brain regions over the early period
      of rat development. Folate concentrations determined at birth were high in all
      brain regions studied. During the first 2 weeks, folate concentrations declined
      steadily, followed by a period of significant increase. High and invariant
      activity of 10-FTHFS was found throughout the period of study. Low amounts of 10
      FTHFDH were seen for the first 2 weeks, but increased significantly from
      postnatal days 14 to 28. These changes correlated with changes determined in the
      concentration of folate, supporting the idea that this protein is involved with
      folate uptake and/or storage. Furthermore, immunohistochemical expression of 10
      FTHFDH in different rat brain regions revealed glial cells as a preferential
      cellular location for this folate-binding protein.

PMID- 10077700
TI  - Reduced levels of a specific myelin-associated oligodendrocytic basic protein
      isoform in shiverer myelin.
AB  - Myelin-associated oligodendrocytic basic protein (MOBP) and myelin basic protein
      (MBP) share many structural similarities. MOBP is synthesised by mature
      oligodendrocytes and localised at the major dense line (MDL), suggesting a role
      in the myelin compaction process. The shiverer mouse, a deletion mutant of the
      myelin basic protein (Mbp) gene, has poorly compacted myelin with essentially no
      MDL. In this study we compare the developmental expression of the Mobp gene in
      wild-type and shiverer mice. The significant finding is that one of the two
      abundant MOBP isoforms, the approximately 20-kD species, is poorly incorporated
      into shiverer myelin. The absence is specific to shiverer and is not a feature of
      dysmyelinating mutants with an abnormal intraperiod line. Our data suggest that
      incorporation of this MOBP isoform into shiverer myelin may be influenced by the
      presence of MBP or be a consequence of a disrupted MDL.

PMID- 10077701
TI  - Postnatal development of dopamine D1-like receptors in rat cortical and
      striatolimbic brain regions: An autoradiographic study.
AB  - Postnatal development of dopamine D1-like (D1/D5) receptors in rat caudate
      putamen (CPu), nucleus accumbens (NAc), hippocampus, frontal and entorhinal
      cerebral cortex was assessed between postnatal days (PD) 7-60 by in vitro
      receptor autoradiography. Density of [3H]SCH-23390 binding to D1-like receptors
      increased from PD-7 to a peak at PD-28 in CPu (11-fold) and NAc (23-fold), then
      declined by 20-40% in both regions over PD-35-60, to adult levels. In
      hippocampus, frontal and entorhinal cortex, D1-like receptors increased by lesser
      amounts (3- to 4-fold) from PD-7 to stable, maximal adult levels at PD-60.
      Evidently, excess D1-like receptors were eliminated during maturation of CPu and
      NAc, but not in the other forebrain regions. Postnatal D1-like receptor
      development in rat forebrain paralleled that of D2- and D4-like receptors in the
      same regions.

PMID- 10077702
TI  - Gephyrin-like immunoreactivity is a marker for growing axons in the central
      nervous system of the immature rat.
AB  - The membrane-associated protein gephyrin can form part of the glycine receptor
      complex at inhibitory synapses. This study provides evidence for gephyrin
      localisation in the developing axons of the rat brain and spinal cord, with
      particular reference to the corticospinal tract. Using a well-characterised
      monoclonal antibody (MAb 7a) gephyrin-like immunoreactivity was found expressed
      by growing axons, disappearing as these axons became myelinated. Immunoelectron
      microscopy localised the antigen to the interior of small, unmyelinated axons in
      the dorsal funiculus of young rats. Western blot analysis of cervical spinal cord
      from different post-natal ages only detected one immunoreactive band at ages when
      immunohistochemistry revealed gephyrin-like immunoreactivity in both the grey
      matter and corticospinal tract. Furthermore, the molecular weight of this band
      corresponded to that of gephyrin, suggesting it is present both at synapses and
      in axons. The known tubulin binding ability of the gephyrin may have a role in
      stabilisation of microtubules in growing axons.

PMID- 10077703
TI  - Malformations of hypothalamic nuclei in hyperinsulinemic offspring of rats with
      gestational diabetes.
AB  - Insulin is a potent modulator of central nervous development and is suggested to
      influence the differentiation and maturation of hypothalamic structures involved
      in the regulation of body weight and metabolism. Hyperinsulinemic offspring of
      mothers with impaired glucose tolerance during pregnancy (gestational diabetes,
      GD) have an increased risk to develop overweight and diabetes mellitus during
      life, while the underlying pathophysiological mechanisms are still unknown. To
      investigate the effects of perinatal hyperinsulinism on the organization of
      hypothalamic regulators of body weight and metabolism, GD was induced in rats by
      application of streptozotocin on the day of conception (25 mg/kg, i.p.). On the
      21st day of life, offspring of GD rats were overweight (p < 0.05) and
      hyperinsulinemic (p < 0.01). Using computer-assisted morphometric measurements,
      significantly decreased mean areas of neuronal nuclei and neuronal cytoplasm
      within the paraventricular hypothalamic nucleus (PVN; p < 0.01) and the
      ventromedial hypothalamic nucleus (VMN; p < 0.05) were observed in GD offspring.
      Analysis of topographically distinct parts revealed that these alterations
      particularly occurred in the parvocellular part of the PVN, as well as in the
      anterior, central, and dorsomedial part of the VMN. No morphometric alterations
      were found within the lateral hypothalamic area and the dorsomedial hypothalamic
      nucleus. In the arcuate hypothalamic nucleus, the mean area of neuronal cytoplasm
      was decreased (p < 0.05), while the number of neurons expressing tyrosine
      hydroxylase was clearly elevated (p < 0.002). For astrocytes, a tendency towards
      an increased glia/neuron ratio was observed in the periventricular hypothalamic
      area. These observations suggest disturbed differentiation and organization of
      distinct hypothalamic nuclei and subnuclei, respectively, in hyperinsulinemic
      offspring of GD rats, possibly leading to dysfunctions of hypothalamic regulators
      of body weight and metabolism which might contribute to the lifelong increased
      risk to develop overweight and diabetogenic disturbances.

PMID- 10077704
TI  - BDNF and NGF afford in vitro neuroprotection against ethanol combined with acute
      ischemia and chronic hypoglycemia.
AB  - Consumption of alcohol during pregnancy can result in central nervous system
      deficits in infants ranging from fetal alcohol effects to fetal alcohol syndrome.
      Changes in cerebral metabolism causing ischemic in utero conditions can also
      result from ethanol (EtOH). Growth factors have been shown to ameliorate ischemic
      damage and EtOH-induced neurotoxicity. However, using an in vitro model system of
      fetal alcohol effects/fetal alcohol syndrome, this study examines the
      neuroprotective effects of nerve growth factor, brain-derived neurotrophic
      factor, or glial cell line derived neurotrophic factor against EtOH treatment (0,
      200, 400, 800, or 1, 600 mg/dl) combined with acute ischemia (2-hour hypoxia in
      EtOH-containing glucose-free media) followed by chronic hypoglycemia (16-hour
      glucose deprivation in EtOH-containing media). 3-(4, 5-Dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assays assessed relative neurotoxicity. Glial cell
      derived neurotrophic factor was not neuroprotective. Nerve growth factor
      protected against ischemia/hypoglycemia combined with 0-1,600 mg/dl EtOH. Brain
      derived neurotrophic factor protected against ischemia/hypoglycemia combined with
      0-800 mg/dl EtOH. These studies demonstrate marked growth factor neuroprotection
      against a myriad of conditions encountered by developing EtOH-exposed fetuses.

PMID- 10077705
TI  - The neuroprotective effects of non-NMDA antagonists in the cerebellum of the
      spastic Han Wistar mutant.
AB  - Excitotoxicity resulting from the dysfunction of glutamate receptors has been
      attributed to neurodegeneration seen in many brain disorders. In our laboratory,
      the spastic Han Wistar mutant is currently utilized as a potential model of
      excitotoxicity. The mutant is characterized by progressive neuronal degeneration,
      hindlimb paresis and ataxia which culminates in the animal's death at
      approximately 65 days of age. In this study, neuroprotection derived from acute
      administration of the non-NMDA antagonist GYKI 52466, and chronic administration
      of the non-NMDA antagonist CNQX was examined in order to determine the potential
      roles of non-NMDA receptors in the observed neurodegeneration. Mutants injected
      with GYKI 52466 (15 mg/kg), twice a week for 3 weeks, exhibited increased life
      spans (14%) and extended motor activity than their vehicle-treated mutant
      siblings. In a separate group of mutants, CNQX (either 50 or 500 microM) was
      infused directly into the third ventricle of the mutant's brain utilizing osmotic
      pumps. A statistically significant increase in motor activity (22%) was detected
      for mutants treated with a dose of 50 microM CNQX compared to their vehicle
      treated siblings. Finally, cerebellar histological evaluations of mutants treated
      with both 50 and 500 microM CNQX showed dose-dependent higher cerebellar Purkinje
      cell counts. These findings suggest that non-NMDA receptors play a significant
      role in neurodegeneration in this animal.

PMID- 10077706
TI  - [Health economic analysis of the effects of including complementary medicine in
      the benefit package of health insurance].
AB  - A randomized experiment was set up in which 7,500 policyholders of Switzerland's
      largest health insurance fund, Helvetia, were offered free supplementary
      insurance for complementary medicine for 3 years. This was meant to simulate a
      situation in which the experimental group had access to the full range of
      complementary medical treatments under their health insurance policies. The
      remaining policyholders in the scheme (670,000 people) formed the control group.
      A third group of policyholders who had taken out additional insurance for
      complementary medical services at their own expense is mentioned only in passing.
      The health insurer's cost and benefit data were analyzed to evaluate the effect
      of the offered free supplementary insurance for complementary medicine. In
      addition, a survey was carried out among random samples of subjects from the
      experimental group and from the control group using the 36-Item Short-Form Health
      Survey (SF-36) to examine the effects of including complementary medicine on
      people's subjective state of health. The analysis of the cost data showed that
      subjects in the experimental group used complementary medicine in addition to
      mainstream medical services. It became also clear that alternative medical
      treatments were given in combination with orthodox medicine; less than 1% of the
      experimental group used exclusively alternative medical services. However, as
      only a very small percentage of the experimental subjects (6.6%) took advantage
      of complementary medicine, no significant impact on overall health cost could be
      inferred. On the other hand, multiple regressions showed that the use of
      complementary medicine had a greater effect on the treatment costs than sex, age
      or language region. Neither at the beginning nor the end of the experiment were
      any significant differences noted in the scales of the SF-36 between the
      experimental and the control group; nor did multiple regressions reveal any
      effects on subjects' state of health due to the inclusion of complementary
      medicine in the basic insurance cover. This study was presented in the media and
      at a public hearing of the Swiss National Science Foundation. It triggered
      numerous valuable discussions. The study design and the conclusions were not left
      uncontested.

PMID- 10077707
TI  - [Motivation for the choice of complementary and mainstream medicine. Patients'
      behavior in a pluralistic medical system].
AB  - The reasons for choosing between various therapeutic possibilities depend in part
      on rational and in part on emotional factors. This project dealt with the
      systematic verification of some decision factors most of which were known
      already. The project was divided in a qualitative and a quantitative part. The
      qualitative segment was based on semistructured interviews with patients of
      general practitioners or of naturopaths. This procedure is often used in
      ethnological research. It identified and evaluated the main motives for the
      individual choices of therapies by the patients. The quantitative part of the
      study was carried out by a procedure often used in social sciences, namely by
      strictly structured telephone interviews of several thousand policyholders of the
      health insurance fund Helvetia. The aim of this part of the study was to verify
      the findings of the qualitative study and to investigate the possible
      significance of additional sociological factors for the choice between different
      therapies. The conclusions drawn from the abundance of data show that a
      widespread use of complementary medicine is a reality. Both parts of the project
      came to the same conclusions. The patients use complementary medicine in a very
      pragmatic way, be it alternately, be it in parallel but not necessarily in
      addition to mainstream medicine. The behavior of the patients is very complex,
      depends on many factors, and can neither be predicted nor easily influenced, not
      even by an additional free insurance for complementary medicine which was offered
      to one of the subgroups of the study (in conjunction with J. Sommer's project 'A
      Randomized Experiment Studying the Effect of Including Complementary Medicine in
      the Mandatory Benefit Package of Health Insurance Funds in Switzerland'). The
      interpretation of the telephone interviews concerning the significance of some of
      the registered sociological factors turned out to be difficult. The project aimed
      primarily at illustrating the use of complementary medicine and at characterizing
      its users.

PMID- 10077708
TI  - [Complementary medicine and health legislation].
AB  - This review begins by explaining the meaning and purpose of health law in
      general. While legal regulations pertinent to mainstream medicine are functioning
      well, this project focuses on the legal situation that developed in Switzerland
      as a consequence of the increasing availability and use of services in
      complementary medicine. There are obvious gaps and deficits in our legislation
      concerning medical and paramedical providers of services in complementary
      medicine. Main emphasis of this project, therefore, was placed on the regulations
      dealing with health professionals in complementary medicine, in particular on
      standards of training, on licenses to practice, and on the compensation by health
      insurance funds. The project achieved a comprehensive stock-taking of the great
      variety of the Swiss federal and the 26 cantonal laws and regulations. It also
      drew conclusions on the necessity to formulate generally applicable rules and
      regulations for the field of complementary medicine and finally submitted a list
      of practical recommendations.

PMID- 10077709
TI  - [Legal status of complementary medicine in Europe].
AB  - As an addition to the project on 'Complementary Medicine and Health Law' carried
      out within the NFP34 it became highly desirable to compare the Swiss legal
      situation with that of most European countries. Therefore, the project compiled
      and analyzed the legal status of 23 European countries concerning the licensing
      regulations for providers of complementary medical services and the corresponding
      reimbursement policies. There are considerable differences between the various
      countries in legal and in practical terms; for the time being a confusing
      situation in view of a possible European harmonization. This project is a first
      step in the direction of a European overview on legal preconditions for the
      provision of and the reimbursement for services in complementary medicine.

PMID- 10077710
TI  - [Mainstream medicine versus complementary medicine (homeopathic) intervention: a
      critical methodology study of care in pregnancy].
AB  - This meticulously evaluated study investigated two fundamental questions. The
      first dealt with the usefulness and adequacy of the instruments (questionnaires
      and case report forms) presently available in mainstream clinical research when
      trying to evaluate two dissimilar therapeutic systems such as main stream
      medicine and homeopathy. The second question dealt with the comparability of the
      two populations of patients in terms of individual personality characteristics as
      well as regarding the progress of the pregnancies and the course of the
      deliveries under the two systems of care and control. It turned out that a study
      of that kind is feasible in principle but is very demanding and time consuming.
      In addition the study showed clearly that the instruments presently available in
      mainstream medicine do not cover essential aspects of homeopathy and, therefore,
      impede a comparison of the two therapeutic systems. In the homeopathic group the
      frequency of situations requiring a Cesarean was remarkably low. However, the
      number of cases is too small to draw qualifying conclusions.

PMID- 10077711
TI  - [Quality of life of pregnant women in homeopathic or mainstream medical type of
      care and the course of the pregnancy].
AB  - This study investigated 120 pregnant women cared for and treated by physicians
      specialized in homeopathy and 85 pregnant women cared for and treated by
      mainstream gynecologists. Quality of life was assessed twice during pregnancy and
      once shortly after delivery by the instrument SEIQoL (Schedule for the Evaluation
      of Individualized Quality of Life). In addition, the study registered individual
      personality characteristics, the psychological situation, the attitude towards
      the forthcoming delivery, and the functional state before and after delivery. It
      turned out that women who preferred homeopathic care judged their quality of life
      lower than women from the other group. However, their criteria for medical
      decisions and for the assessment of their own personal situation differed as
      well. There was some correlation between quality of life and age, number of
      deliveries, partnership and certain personality characteristics. The study showed
      the importance of paying more attention to the subjective world of the pregnant
      women. This applies especially in an analysis of two dissimilar therapeutic
      systems. It could also be concluded that the SEIQoL was a useful instrument for
      such a study. Finally it turned out that the two populations investigated were
      different.

PMID- 10077712
TI  - [Acupuncture and bronchial asthma].
AB  - The 66 randomized patients with mild bronchial asthma who took part in this study
      were divided into three nearly equal groups. Group one was treated with true
      acupuncture during the first and the fourth month (up to week 16). Group two was
      treated similarly but needled at non-acupuncture points. The third group served
      as a control. All patients were allowed to maintain their normal asthma
      medication with the recommendation to keep the regimen unchanged until week 20,
      i. e. 4 weeks after termination of the specific treatment. The changes in peak
      flow variability up to week 16 served as main outcome criterion. Additional
      parameters included several spirometric analyses as well as various markers in
      blood and sputum that are specific for the allergic inflammatory reaction of the
      upper respiratory tract. The values measured showed considerable individual
      variability. This impeded the demonstration of efficacy. In conclusion it can be
      stated that there was a consistent, positive yet unspecified effect of the
      needling in both treated groups which can be interpreted as a trend in affecting
      the asthmatic condition. This effect could have been more pronounced or even
      clinically relevant for certain individuals had one considered a separate
      analysis of the data of each patient.

PMID- 10077713
TI  - [Acupuncture and insomnia].
AB  - 40 patients with primary difficulties in either falling asleep or remaining
      asleep were diagnosed according to the traditional Chinese medicine, allocated to
      specific diagnostic subgroups and treated individually by a practitioner in his
      private practice. The patients were randomized into two groups, one receiving
      true acupuncture, the other needled at non-acupuncture points for 3-5 sessions at
      weekly intervals. The outcome of the therapy was assessed in several ways, first
      and foremost by an objective measurement of the sleep quality by polysomnography
      in a specialized sleep laboratory, performed once before and once after
      termination of the series of treatments. Additional qualitative results were
      obtained from several questionnaires. The objective measurement showed a
      statistically significant effect only in the patients who received the true
      acupuncture. The subjective, qualitative assessment was better in the proper
      treatment group than in the control group but was not calculated statistically
      for methodological reasons. Based on the results of this study, it can be
      concluded that true and individualized acupuncture indeed shows efficacy in
      primary sleep disorders. However, a direct influence by the therapist cannot be
      excluded.

PMID- 10077714
TI  - [Demonstration of the effective of acupuncture on the autonomic nervous system by
      examination of the microcirculation].
AB  - This study served to compare the effect of needling at true acupuncture points
      with that of needling at non-acupuncture points. Various parameters were used to
      quantify the results such as measurement of the peripheral blood circulation in
      finger tips and the nasal mucous membrane, measurement of the skin temperature at
      various sites of the body by means of infrared thermography or contact
      thermometry, testing of skin conductance, or recording of heart frequency and
      respiration. These are all indicators of the functional state of the autonomic
      nervous system. This model experiment was performed on healthy volunteers and
      showed identical, transient, quick reflex responses of the sympathetic nervous
      system after true acupuncture as well as after needling at non-acupuncture
      points. These reactions are related to pain and do not allow to draw any
      conclusions on the specificity of the points that were needled. The aim of this
      project was not to make a statement about the therapeutic efficacy of
      acupuncture. It was meant to be a model allowing the study of some basic
      regulatory mechanisms which are fundamental for most treatments in complementary
      medicine.

PMID- 10077715
TI  - [Quality of life of patients with metastatic breast or intestinal cancer, treated
      with anthroposophic medicine or with mainstream medicine, the latter with or
      without psycho-oncologic or supplementary anthroposophic therapy].
AB  - This project dealt with two subjects. On the one hand, the measurement of the
      quality of life of cancer patients which needed to be further refined in order to
      assess the usefulness and efficacy of a treatment by complementary medicine. On
      the other hand, it was important to know whether severely ill cancer patients
      treated in an anthroposophical clinic would differ from equally ill patients in a
      university hospital in terms of attitude towards their illness and in terms of
      clinical diagnosis. Finally, an attempt was made to demonstrate an improvement of
      quality of life in conventionally treated patients of the university hospital,
      who were offered an additional treatment either with a supportive-expressive
      group therapy or with an anthroposophical therapy. More than 500 patients
      participated in the study. There were marked sociodemographic and medical
      differences between the patients of the anthroposophical clinic and those of the
      university hospital. In addition, it seems that spiritually oriented and active,
      problem-oriented coping contribute a lot to the quality of life. It was not
      possible to truly compare the value of the two additional therapies offered to
      the patients at the university hospital because patient accrual was much slower
      than anticipated and many patients left the study too early for health reasons or
      death.

PMID- 10077716
TI  - [Foot reflexology massage: a clinical study].
AB  - The aim of the study was to investigate the possible usefulness of foot
      reflexology on the recovery after a surgical intervention. 130 patients
      participated in the study. They underwent abdominal surgery under full anesthesia
      for different, but exclusively gynecological reasons. Foot reflexology
      investigated in this study was applied only for a few days for each patient. The
      following parameters were recorded: the subjective, self-assessed, general
      condition, pain intensity, movement of the bowels, micturition and sleep,
      beginning on the day before operation until day 10. Two other treatments served
      as controls, a simple massage of the foot or a personal conversation. The simple
      massage turned out to be a relaxing, positive experience, whereas foot
      reflexology had various effects, some of them were even negative. The conclusion
      was that foot reflexology is not recommended for acute, abdominal postsurgical
      situations in gynecology because it can occasionally trigger abdominal pain. This
      project is one of the few studies planned, conducted and performed by the nursing
      staff.

PMID- 10077717
TI  - [Hypnosis and self-hypnosis administered and taught by nurses for relief of
      chronic pain: a controlled clinical trial].
AB  - In this controlled clinical trial hypnosis and self-hypnosis were evaluated when
      used as an adjuvant treatment to instrumental and pharmacological management of
      chronic pain. The study took place in a hospital specialized in the treatment of
      outpatients suffering from chronic pain. Hypnosis and self-hypnosis were
      administered and taught by nurses who had been trained just recently for this
      very purpose. Under the conditions of the study it was not possible to measure an
      effect of hypnosis on pain despite some subjective feeling of usefulness.
      However, it should be taken into account that this form of adjuvant therapy was
      used for the first time in that hospital for the purpose of the study and,
      therefore, took place in an artificial setting. It could well be that the same
      therapy administered in the proper therapeutic environment of a specialized
      institution could show beneficial effects on pain.

PMID- 10077718
TI  - [Clinical hypnotherapy/self-hypnosis for unspecified, chronic and episodic
      headache without migraine and other defined headaches in children and
      adolescents].
AB  - Chronic and episodic headaches in children and adolescents are a common problem.
      Therefore, the growing resistance against frequent use of drugs is quite
      justified. This study was initiated in search for other helpful therapeutic
      approaches. The aim was to compare the effect of 5 sessions of hypnosis/ self
      hypnosis given at weekly intervals and lasting half an hour each with two
      psychological treatments requiring the same amount of time, namely behavior
      therapy and talks to the doctor. Despite the small number of patients, both types
      of treatments were effective. However, the hypnosis/self-hypnosis seems to be
      superior not only in terms of frequency and intensity of the headaches but also
      concerning the patients' ability to keep their headaches and their well-being
      under control.

PMID- 10077719
TI  - [Effect of self-hypnosis in patients with pollinosis].
AB  - The aim of this study in hypnosis was the exemplary verification of a regulatory
      intervention in patients with pollinosis. Hypnosis and self-hypnosis are
      established methods in medicine. 52 patients with pollinosis participated in this
      clinical study. It lasted over two pollen seasons. Self-hypnosis was learned
      quite easily. It resulted in a clear yet statistically weak beneficial effect on
      the subjective assessment of the pollinosis symptoms, on the consumption of drugs
      and on other objective findings. From a methodological point of view this study
      might suggest that the classical comparison of experimental groups in clinical
      research could hide some larger therapeutic effects in individual patients.
      Therefore, it would be desirable to consider also individual data analysis in all
      future studies dealing with psychological or psychosomatic mechanisms and in all
      studies which capture parameters interactive at different levels. The beneficial
      effect of hypnosis on the swelling of the nasal mucous membrane in a provocation
      test initiated a subsequent small project on the possible mode of action of
      hypnosis in this pollinosis study. However, the results were inconclusive.

PMID- 10077720
TI  - [Bioresonance therapy (biophysical information therapy) in stuttering children].
AB  - This study tried to investigate whether bioresonance therapy could have a
      beneficial effect in stuttering children of school age who showed no progress
      under other therapies. The 14 patients, age 9-18 years, were randomized in two
      groups. The first received 10 sessions of bioresonance, the second continued with
      speech therapy. In the second phase of the study the first group received speech
      therapy while the second was treated by bioresonance. The intensity of the
      stuttering was measured at the beginning, at mid-term and at the end of the 9
      months experiment. Various established methods were used for that purpose. It was
      not possible to demonstrate any improvement of the stuttering during or after
      either of the two therapies. This study showed how difficult it is to investigate
      stuttering scientifically. It turned out that in reality there is a lack of
      precise differential diagnosis. This means that true stuttering can hardly be
      distinguished from other speech disturbances and is under the influence of
      countless external factors.

PMID- 10077721
TI  - [Electromyographic measurement of human muscles depending on position to
      radiesthetically defined attraction zones compared with neutral zones].
AB  - Experienced dowsers were able to localize radiesthetically defined zones with
      statistically highly significant accuracy in blind and double-blind experiments.
      The transition from neutral to active zones and vice-versa could be demonstrated
      electromyographically on various arm muscles of sensitive persons. Thus, there is
      most likely a relationship between an active zone and certain functions of the
      human body. This project deals with basic research, it does not examine possible
      causes of diseases. Nevertheless, the often postulated influence of active zones
      on health is part of the background of the project.

PMID- 10077722
TI  - [Conclusion].

PMID- 10077723
TI  - [Medicine and medical concepts].
AB  - Any discussion on the future of medicine has to deal with the healer's art based
      on cultural values and with the individual situation of the patients, their
      perception and concept of health and disease, their hopes, intentions and life
      projects. Medicine and health care are of fundamental importance in all
      societies, so their task goes far beyond the traditional academic discipline. As
      well as repairing localized damage with the usual technical and chemical
      instruments one may also use the regulatory measures of complementary medicine to
      stimulate the system's self-organization. Over and above this, healing means
      changing the patient's self-concepts, his concepts of health and disease,
      changing his behavior, and adapting his life projects and targets. The treatment,
      therefore, should be experienced by the patient as part of his life, and
      therapeutic interventions as well as the diagnostic interpretation are to be seen
      as structuring elements of the healing process, besides, of course, being helpful
      in the overcoming of the disease. Healing does not happen in a void, but within a
      therapeutic setting, a sort of subcultural unit which includes the therapist, and
      is based on a common understanding of the illness and a common will to overcome
      it. The therapeutic setting is an integrative part of regulatory treatment, and
      evaluation procedure must be designed in a way that the questions asked are
      consistent with the specific individual reality of the setting and the evaluation
      has no impact on the setting as such. Therefore, research cannot be done by the
      therapist since he is part of the setting, but must be undertaken by independent
      observation of the setting as a whole from outside. The projects of the
      Nationales Forschungsprogramm 34 (NFP34) provide an overview of adequate and
      inadequate concepts and methods for future structured evaluation of complementary
      medicine. Whether or not the results of the NFP34 will be helpful in advancing
      medicine depends on the possibility of creating an appropriate research mentality
      in this new field within the medical community and to establish ongoing projects.
      Some important concepts of approaching complementary medicine have not been
      evaluated, e. g. historical, ethnological, sociological and pragmatic methods. As
      some methods of complementary medicine actually have been integrated into the
      official curricula, ongoing re-evaluation is mandatory to assure the conherence
      in teaching and practice. Research into complementary medicine which often has
      its roots in other times and in other cultures must be designed in such a way
      that it covers the method's specific cultural concepts as well as the thinking
      patterns of public medicine today.

PMID- 10077724
TI  - True pedigree errors more frequent than apparent errors for single nucleotide
      polymorphisms.
AB  - Single nucleotide polymorphisms (SNPs) are currently being developed for use in
      disequilibrium analyses. These SNPs consist of two alleles with varying degrees
      of polymorphism. A natural design for use with SNPs is the 'haplotype relative
      risk' sampling design in which a father, mother, and child are typed at an SNP
      locus. Given such a trio of genotypes, we ask: what is the probability that a
      pedigree error (a change from one allele to the other) at an SNP locus will be
      detected using only Mendel's laws as a check? We calculate the probability of
      detecting such errors for a hypothetical SNP locus with varying degrees of
      polymorphism and for various true error rates. For the sets of allele frequencies
      considered, we find that the detection rates range between 25 and 30%, the
      detection rate being lowest when the two alleles have equal frequencies and the
      highest when one allele has a frequency of 10%. Based on this detection rate, we
      determine that the true error rate is roughly 3.3-4 times that of the apparent
      error rate at an SNP locus. The greatest discrepancy between true and apparent
      error rates occurs when allele frequencies are equal.

PMID- 10077725
TI  - Molecular genetic study of autosomal dominant retinitis pigmentosa in Lithuanian
      patients.
AB  - Lithuanian patients with visual problems were clinically examined for retinitis
      pigmentosa (RP). A total of 33 unrelated families with autosomal dominant RP
      (adRP) were identified. Screening for mutations in the rhodopsin (RHO) and
      peripherin/RDS (RDS) genes was performed using DNA heteroduplex analysis. Direct
      DNA sequencing in the cases of heteroduplex formation showed the presence of the
      following mutations and polymorphisms in 14 adRP patients: RHO gene - Lys248Arg
      (1 case), and Pro347Leu (2 cases); RDS gene - Glu304Gln (12 cases), Lys310Arg (5
      cases), and Gly338Asp (12 cases). The presence of these mutations (except
      Lys248Arg in the RHO gene) was confirmed by relevant restriction enzyme
      digestion. The frequency of the RDS gene mutations Glu304Gln and Gly338Asp was
      estimated to be 36.4%, while mutation Lys310Arg was less frequent (15.2%). These
      3 RDS gene mutations appear to be polypeptide polymorphisms not related to adRP.

PMID- 10077726
TI  - Human NDUFB9 gene: genomic organization and a possible candidate gene associated
      with deafness disorder mapped to chromosome 8q13.
AB  - Human NADH dehydrogenase (ubiquinone) 1beta-subcomplex, 9 (NDUFB9) is a nuclear
      encoded mitochondrial protein with the respiratory electron transport chain. It
      has been physically mapped to a 1-Mb deletion at chromosome 8q13 which also
      contains the gene for branchio-oto-renal (BOR) syndrome. BOR syndrome is
      characterized by branchial and renal abnormalities with hearing impairment. Since
      several hereditary deafness disorders have been associated with mitochondrial
      mutations, NDUFB9 was considered a candidate gene for BOR syndrome. Recently,
      EYA1 gene has been identified in the region which underlies the BOR syndrome but
      majority of BOR families did not show mutations in the EYA1 gene. Here we have
      determined the genomic structure of the NDUFB9 gene, including the nucleotide
      sequence, organization and the boundaries of the four coding exons. PCR primers
      were designed from the adjacent intron sequences that allow amplification of the
      four exons that encode the complete open reading frame. To identify whether
      mutations in NDUFB9 are involved in causing the BOR syndrome, we screened 9 BOR
      families which did not show mutations in the EYA1 gene by heteroduplex analysis;
      however, no mutations were found.

PMID- 10077727
TI  - Analysis of the complete coding region of the CFTR gene in ten Algerian cystic
      fibrosis families.
AB  - The spectrum of cystic fibrosis (CF) mutations in the North African population
      remains poorly known. In order to offer an effective diagnostic service and to
      determine accurate risk estimates, we decided to identify the CF mutations in 10
      Algerian CF families. We carried out a chemical-clamp denaturing gradient gel
      electrophoresis analysis of the CFTR gene and automated direct DNA sequencing. We
      identified 5 mutations and we characterized 60% of the CF chromosomes. Taking
      advantage of the homogeneity of the sample, we report clinical features of
      homozygous CF patients.

PMID- 10077728
TI  - Contribution of interleukin 1beta and KM loci to alopecia areata.
AB  - Alopecia areata is a common skin disease in which proinflammatory cytokines such
      as IL-1beta may play a pathogenic role. In this study, we examined the
      distribution of genotypes of an IL-1beta single base change polymorphism at
      position +3953 in patients with alopecia areata. The distribution of
      immunoglobulin kappa light chain (KM) genotypes was similarly examined. The data
      obtained showed that the IL-1beta and KM loci act cooperatively to significantly
      increase susceptibility to alopecia areata.

PMID- 10077729
TI  - Linkage disequilibrium and haplotype analysis in German Friedreich ataxia
      families.
AB  - The main mutation causing Friedreich ataxia (FRDA) is the expansion of a GAA
      repeat localized within the intron between exon 1 and exon 2 of the gene X25.
      This expansion has been observed in 98% of FRDA chromosomes. To analyze
      frequencies of markers tightly linked to the Friedreich ataxia gene and to
      investigate wheter a limited number of ancestral chromosomes are shared by German
      FRDA families, a detailed analysis employing nine polymorphic markers was
      performed. We found strong linkage disequilibria and association of FRDA
      expansions with a few haplotypes. FRDA haplotypes differ significantly from
      control haplotypes. Our results confirm that GAA repeat expansions in intron 1 of
      the frataxin gene are limited to a few chromosomes and indicate an obvious
      founder effect in German patients. Based on these analyses, we estimate a minimum
      age of the mutation of 107 generations.

PMID- 10077730
TI  - Hereditary desmoid disease in a family with a germline Alu I repeat mutation of
      the APC gene.
AB  - Two families with autosomal dominantly inherited desmoid tumors have recently
      been shown to have germline mutations at the 3' end of the APC gene. We
      subsequently identified an Amish family with autosomal dominantly inherited
      desmoid tumors. Genetic analysis performed on one family member, a 47-year-old
      man with multiple desmoid tumors and no colon polyps, revealed a protein
      truncating mutation in the middle of the APC gene. The truncating mutation is the
      result of a 337-bp insertion of an Alu I sequence into codon 1526 of the APC
      gene. The presence of a poly(A) tail at the 3' end of the insertion suggests that
      the Alu I sequence was inserted by a retrotranspositional event. Germline
      insertions of Alu I sequences have occasionally been reported to cause other
      genetic diseases including type I neurofibromatosis, hereditary site-specific
      breast cancer (BRCA2), and hemophilia B. However, this is the first report of a
      germline mutation of the APC gene resulting from an Alu I insertion.

PMID- 10077731
TI  - No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter
      and the density of frontal cortical 5-HT2A receptors in schizophrenia.
AB  - The A(-1438)G promoter polymorphism of the 5-hydroxytryptamine 2a receptor (5
      HT2AR) gene and its influence on the cortical density of 5-HT2AR was studied
      using brain tissue donated at autopsy from 58 schizophrenic and 64 non
      schizophrenic subjects. A linkage between genotypes for the A(-1438)G and a T102C
      polymorphic site identified in a previous study was observed. Our data suggest no
      association of the A(-1438)G polymorphism with schizophrenia and no effect of the
      promoter genotype upon 5-HT2AR densities in either the schizophrenic or non
      schizophrenic groups.

PMID- 10077732
TI  - A principal-components approach based on heritability for combining phenotype
      information.
AB  - For many traits, genetically relevant disease definition is unclear. For this
      reason, researchers applying linkage analysis often obtain information on a
      variety of items. With a large number of items, however, the test statistic from
      a multivariate analysis may require a prohibitively expensive correction for the
      multiple comparisons. The researcher is faced, therefore, with the issue of
      choosing which variables or combinations of variables to use in the linkage
      analysis. One approach to combining items is to first subject the data to a
      principal components analysis, and then perform the linkage analysis of the first
      few principal components. However, principal-components analyses do not take
      family structure into account. Here, an approach is developed in which family
      structure is taken into account when combining the data. The essence of the
      approach is to define principal components of heritability as the scores with
      maximum heritability in the data set, subject to being uncorrelated with each
      other. The principal components of heritability may be calculated as the
      solutions to a generalized eigensystem problem. Four simulation experiments are
      used to compare the power of linkage analyses based on the principal components
      of heritability and the usual principal components. The first of the experiments
      corresponds to the null hypothesis of no linkage. The second corresponds to a
      setting where the two kinds of principal components coincide. The third
      corresponds to a setting in which they are quite different and where the first of
      the usual principal components is not expected to have any power beyond the type
      I error rate. The fourth set of experiments corresponds to a setting where the
      usual principal components and the principal components of heritability differ,
      but where the first of the usual principal components is not without power. The
      results of the simulation experiments indicate that the principal components of
      heritability can be substantially different from the standard principal
      components and that when they are different, substantial gains in power can
      result by using the principal components of heritability in place of the standard
      principal components in linkage analyses.

PMID- 10077733
TI  - Linkage information content of polymorphic genetic markers.
AB  - The Polymorphism Information Content (PIC) value is often used to measure the
      informativeness of a genetic marker for linkage studies. The PIC value was first
      derived for the case of a rare dominant disease, when one of the parents is
      affected, and is a function of the particular mode of disease inheritance. We
      first generalize the definition of the PIC value in such a way that it does not
      depend on the mode of inheritance of the trait being studied, and then develop a
      Linkage Information Content (LIC) value to measure the informativeness of a
      marker about the identity-by-descent sharing status of particular types of pairs
      of relatives. Knowing the LIC value, it is possible to determine the effective
      number of fully informative pairs in a study when we have incomplete marker
      information.

PMID- 10077734
TI  - A novel splice site mutation in a Brazilian patient with hereditary antithrombin
      deficiency type I.

PMID- 10077735
TI  - A novel nonsense mutation 6, E - X in the protein S gene causes type I
      deficiency.

PMID- 10077736
TI  - Effects of imidazoline and non-imidazoline alpha-adrenergic agents on canine
      platelet aggregation.
AB  - Aggregatory and antiaggregatory effects of imidazol(in)e and non-imidazol(in)e
      alpha-adrenergic agents on canine platelets were examined turbidimetrically in
      citrated platelet-rich plasma or washed platelet solution. Each alpha
      adrenoceptor agonist alone did not induce aggregation, but adrenaline and
      noradrenaline potentiated dose-dependently aggregation stimulated by ADP,
      collagen or thrombin. Small potentiation of ADP- or collagen-stimulated
      aggregation was also observed in response to oxymetazoline. The alpha2
      adrenoceptor antagonists and/or imidazol(in)e alpha-adrenergic agents inhibit
      dose-dependently adrenaline-potentiated aggregation, whereas alpha1-adrenoceptor
      antagonists, a beta-adrenoceptor antagonist and non-imidazol(in)e alpha
      adrenergic agents were no or less effective in inhibiting adrenaline-potentiated
      aggregation. The alpha2-adrenoceptor agonists did not reduce inhibitory effect of
      alpha2-adrenoceptor antagonists for adrenaline-potentiated aggregation. The
      alpha2-adrenoceptor antagonists and/or imidazol(in)es were no or less effective
      in inhibiting aggregation induced by ADP or thrombin alone. These results
      demonstrated that alpha2-adrenoceptor-blocking agents and/or imidazol(in)e alpha
      adrenergic agents inhibit effectively the adrenaline-potentiated platelet
      aggregation.

PMID- 10077737
TI  - Identification of binding sites of bopindolol and its two metabolites with beta1
      adrenoceptors by molecular modeling: comparison with beta2 adrenoceptors.
AB  - This study was designed to examine the importance of interaction in the bindings
      of nonselective beta-blockers to beta1-adrenoceptors (beta1-ARs) as compared with
      beta2-ARs, using molecular modeling. The beta-blockers used in this study were
      bopindolol [4-(benzoyloxy-3-t- butylaminopropyl)-2-methylindol hydrogen
      malomate], its two metabolites [18-502 - hydrolyzed bopindolol or 4-(3-t
      butylamino-2-hydroxypropoxy)-2-methyl indole - and 20-785 - 4-(3-t
      butylaminopropoxy)-2-carboxyl indole], and propranolol. Molecular modeling was
      performed on an Indigo2 workstation (Silicon Graphic) using Discover/Insight II
      (Molecular Simulations) software. Through molecular modeling, possible binding
      sites for these drugs were suggested to lie between helices 3, 4, 5, and 6 of the
      beta1-AR. The amine, benzoic acid, indole methyl, t-butyl, phenyl, and indole
      functional groups of bopindolol possibly interact with Asp138 (transmembrane - TM
      - 3), Ser190 (TM 4), Ala343 (TM 6), Val137 (TM 3), Pro339 (TM6), Cys336 (TM 4),
      Leu237 (TM 5), and Pro236 (TM 5) of beta1-AR, respectively, by either hydrogen
      bonding or hydrophobic interactions. In addition, 18-502, 20-785, and propranolol
      also interacted with sites at the same positions as those of beta2-ARs. Thus, the
      results of the present study suggested that although Ala343 and Val137 of beta1
      AR among these amino acids were different from those of beta2-AR, the
      interactions at the same sites between ligands and amino acids of beta1-AR as
      those of beta2-ARs may occur because these drugs are nonselective.

PMID- 10077738
TI  - Site-specific effects of the nonsteroidal anti-inflammatory drug lysine
      clonixinate on rat brain opioid receptors.
AB  - In addition to effects in the periphery through inhibition of prostaglandin
      synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory
      drugs (NSAIDs) act in the central nervous system. The possibility that the
      central action of NSAIDs involves regulation of opioid receptors was investigated
      by quantitative autoradiography of mu, delta, and kappa sites in rat brain
      slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic
      nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10
      days with lysine clonixinate. Labeling of delta receptors was lower in the
      lateral septum, and kappa sites decreased in thalamic nuclei. These effects were
      not mediated through direct interaction with opioid-binding sites, since receptor
      binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(
      4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central
      effects of NSAIDs might, therefore, involve interaction with the opioid receptor
      system through indirect mechanisms.

PMID- 10077739
TI  - Age-related expression of renal thrombospondin 1 mRNA in F344 rats: resemblance
      to diabetes-induced expression in obese Zucker rats.
AB  - Age-related increases occurred in renal thrombospondin 1 (TSP1) mRNA in F344
      rats, resembling diabetes-induced TSP1 mRNA in the obese Zucker rat. TSP1 mRNA
      was 3.5-fold higher in 24-month-old than in 3-month-old F344 rats. TSP1 mRNA
      increased similarly in 5-month-old obese Zucker rats as compared with lean
      littermates and correlated positively with the extent of proteinuria (r = 0.71).
      In situ hybridization identified elevated TSP1 mRNA levels in epithelial cells of
      distended tubules as well as in interstitium near dilated tubules of both 24
      month-old F344 rats and 5-month-old obese Zucker rats. Furthermore, thrombin
      increased TSP1 mRNA in mesangial and epithelial cells in culture, indicating that
      thrombin may contribute to elevated TSP1 expression in renal disease. Thrombin
      increased TSP1 mRNA within 30 min after treatment which required de novo
      synthesis of protein. The thrombin receptor tethered ligand peptide, SFLLRN,
      increased TSP1 mRNA, indicating that the thrombin-induced increase in TSP1 mRNA
      was due to direct thrombin receptor (PAR1) stimulation. These results show that
      increased TSP1 mRNA levels are a component of interstitial fibrosis seen in aged
      and diabetic kidneys and suggest that similar pathological changes occur in
      kidneys of aging and diabetic rats.

PMID- 10077740
TI  - Effects of zinc acexamate (NAS-501) on superoxide radicals and lipid peroxidation
      of rat gastric mucosa.
AB  - Zinc acexamate (NAS-501), an anti-ulcer agent, has been reported to prevent
      various acute experimental gastric mucosal lesions and duodenal ulcers in rats.
      In order to clarify the mechanisms by which NAS-501 exhibits the anti-ulcer
      effects, we investigated the anti-oxidative effects of NAS-501 in vitro and in
      vivo. NAS-501 significantly reduced the superoxide radical-dependent
      chemiluminescence, generated by hypoxanthine-xanthine oxidase, rat neutrophils
      and guinea-pig macrophages in vitro. These in vitro effects were also confirmed
      by electron spin resonance using a 5, 5-dimethyl-1-pyrroline-N-oxide spin
      trapping method. In addition, NAS-501 significantly inhibited lipid peroxidation
      induced by increasing concentrations of Fe2+/ascorbate in rat gastric mucosal
      homogenate in vitro. Oral administration of NAS-501 (30 mg/kg) significantly
      inhibited production of thiobarbituric acid-reactive substance in rat gastric
      mucosa following per os instillation of 60% ethanol in 150 mmol/l HCl in vivo.
      These results suggest that NAS-501 exhibits the preventive effect from acute
      gastric mucosal lesions by the anti-oxidative activity.

PMID- 10077741
TI  - Aqueous humor dynamics in anesthetized rats infused with intracameral
      apraclonidine.
AB  - We studied the acute effects of the ocular hypotensive drug, apraclonidine (AP),
      on intraocular pressure (IOP) and aqueous humor dynamics of anesthetized rats
      during infusion-induced ocular hypertension. Two infusions were made into the
      anterior chamber of the eye: one was constant at a rate of 0.05 microl/min, the
      other was cyclic, at a rate of 0.25 microl/min, with the pump on for 4 min, then
      off for 4 min. Data were processed by complex demodulation and analysis of a
      second-order transfer function. This permitted separate calculations of resistive
      components (Ao), i.e., trabecular meshwork and uveoscleral outflows, and residual
      pressure (RP) estimating nonresistive components, i.e., aqueous synthesis and
      episcleral venous pressure. A balanced salt solution (BSS) and AP (0. 0005%) were
      tested. AP markedly delayed the within-group rise in IOP: 20 min for BSS vs. 60
      min for AP (p < 0.001). IOP of AP rats was less than control for 100 min (p <
      0.05). The infusions raised Ao in both groups (p < 0.05). AP initially had a
      transient inhibitory effect (p < 0.05). Infusions raised RP in both groups. AP
      had a strong inhibitory effect for the first 8 cycles (p < 0.05). These data
      document that the acute effects of AP in this in vivo rat model of ocular
      hypertension were to delay increases in IOP, mainly by reducing nonresistive
      components of aqueous humor dynamics. Transient inhibition of resistive
      mechanisms also occurred.

PMID- 10077742
TI  - Developing hypothalamic dopaminergic neurones as potential targets for
      environmental estrogens.
AB  - Environmental chemicals which mimic the actions of estrogen have the potential to
      affect any estrogen responsive tissue. The aim of the present study was to
      investigate their potential to mimic the effects of 17beta-estradiol (E2) on
      developing primary rat hypothalamic dopaminergic (DA) neurones maintained in a
      chemically defined medium. We now show that both E2 and octylphenol (OP), but not
      the non-aromatizable androgen, dihydrotestosterone, enhanced the uptake of [3H]DA
      by the cultured cells, whereas they had no effect on the uptake of [14C]GABA.
      Although the sensitivity of responses may change with the age of the developing
      cultures, the dose response curves for E2 and OP were typically 'bell-shaped',
      with a rise in response followed by a decline to control levels with increasing
      concentrations. Effects were seen as low as 10(-14) M for E2 and 10(-11) M for
      OP. Responses to E2 (10(-12) M) and OP (10(-9) M) were reversed in the presence
      of the antiestrogen, ZM 182780 (10(-5) M). This study thus provides direct
      evidence, using a mechanistic rather than toxicological end-point, in support of
      the hypothesis that inappropriate exposure to environmental estrogens at
      critically sensitive stages of development, could potentially perturb the
      organisational activities of estrogen on selected neuronal populations in the
      CNS.

PMID- 10077743
TI  - The effect of the orexins on food intake: comparison with neuropeptide Y, melanin
      concentrating hormone and galanin.
AB  - Orexin-A and orexin-B (the hypocretins) are recently described neuropeptides
      suggested to have a physiological role in the regulation of food intake in the
      rat. We compared the orexigenic effect of the orexins administered
      intracerebroventricular (ICV) with other known stimulants of food intake, one
      strong, neuropeptide Y (NPY), and two weaker, melanin-concentrating hormone (MCH)
      and galanin. Orexin-A consistently stimulated food intake, but orexin-B only on
      occasions. Both peptides stimulated food intake significantly less than NPY, but
      to a similar extent to MCH (2 h food intake: NPY 3 nmol, 7.2+/-0.9 g vs saline,
      1.5+/-0.2 g, P<0.001, MCH 3 nmol, 3.2+/-0.8 g vs saline, P<0.01, orexin-B 30
      nmol, 2. 6+/-0.5 g vs saline, P=0.11) and to galanin (1 h food intake: galanin 3
      nmol, 2.0+/-0.4 g vs saline, 0.8+/-0.2 g, P<0.05, orexin-A 3 nmol 2.2+/-0.4 g vs
      saline, P<0.01; 2 hour food intake: orexin-B 3 nmol, 2.4+/-0.3 g vs saline, 1.3+/
      0.2 g, P<0.05). Following ICV orexin-A, hypothalamic c-fos, a maker of neuronal
      activation, was highly expressed in the paraventricular nucleus (PVN), and the
      arcuate nucleus (P<0.005 for both). IntraPVN injection of orexin-A stimulated 2 h
      food intake by one gram (orexin-A 0.03 nmol, 1.6+/-0. 3 g vs saline, 0.5+/-0.3 g,
      P<0.005). These findings support the suggestion that the orexins stimulate food
      intake. However, this effect is weak and may cast doubt upon their physiological
      importance in appetite regulation in the rat.

PMID- 10077744
TI  - Recombinant human thyroid peroxidase expressed in insect cells is soluble at high
      concentrations and forms diffracting crystals.
AB  - Human thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis, can
      be produced in active form in the High Five insect cell line and when purified
      from the cell culture medium is soluble at concentrations of up to 18 mg/ml. This
      contrasts to a recent report in which human TPO produced in insect cells was
      found to be insoluble at high concentrations. Our concentrated TPO grows trigonal
      trapezohedral crystals of up to 0.5 mm in length in a vapour diffusion apparatus
      using polyethelene glycol as a precipitant. The crystals diffract X-rays to a 6 A
      resolution and the diffraction data from the crystals have been analysed giving
      unit cell dimensions. A potential molecular replacement solution has been
      identified using myeloperoxidase (MPO) as a phasing model.

PMID- 10077745
TI  - New acquisitions in Helicobacter pylori infection. Introduction.

PMID- 10077746
TI  - New concepts concerning management of Helicobacter pylori infection: 2 years
      after the Maastricht Consensus Report.

PMID- 10077747
TI  - Confounding factors in observational and intervention studies.
AB  - In studying the association of Helicobacter pylori with any particular illness,
      it is essential to consider the effects of confounding. The methods of dealing
      with confounding, a situation in which there is a true association of a risk
      factor and a disease, and the association is not causal, include matching during
      the design and carrying out of the study, or stratification and adjustment during
      the analysis. Adjustment during analysis of data collected in observational
      studies can reduce the effects of confounding. However, multivariate models are
      seriously limited in their ability to control for confounding, especially when
      covariates are imprecisely measured.

PMID- 10077748
TI  - New acquisitions in Helicobacter pylori characteristics.
AB  - The protection of Helicobacter pylori from the gastric acid exerted by urease is
      based on an increase of the bacterial periplasmic pH and membrane potential.
      Ammonia generated from urea induces apoptosis of gastric cells in vitro, and
      inhibits gastric somatostatin release in animals, which could have consequences
      on the physiology of digestion in general. The type s1/m1 structure of the vacA
      gene is associated with the production of high levels of cytotoxin. Strains with
      m2 region type, formerly considered devoid of toxic activity, are fully toxic
      when assayed with cell lines other than HeLa cells, which possibly lack receptors
      for m2 VacA type. The enhanced gastric mucosa damage associated with infection by
      cytotoxic organisms could be explained by the varying of effects exerted by VacA
      on target cells: extracellular secretion of acidic hydrolases, cytoskeletal
      alterations, actin rearrangement, reduction of epidermal growth factor binding to
      its receptor, inhibition of the stimulation of CD4+ T cells proliferation induced
      by the antigen presenting cells. Organisms that possess the pathogenicity island
      cag (cag+) induce an increased inflammation and transduction of signals to the
      host cells; however, they reduce the apoptosis of colonised cells. The results of
      an investigation on the possible influence of a variable cagA status on the
      extension of apoptosis have indicated that this kind of programmed death is
      disengaged from the possession of cagA by Helicobacter pylori organisms
      colonising the same gastric areas. It is likely that the whole pathogenic
      potential of cag+ organisms is far from being completely explored, as suggested
      by the recent finding that the expression of a bacterial adhesin (called BabA)
      involved in binding to the blood group antigen Lewis b is associated with the
      presence of cag.

PMID- 10077749
TI  - Helicobacter pylori LPS: molecular mimicry with the host and role in
      autoimmunity.
AB  - Helicobacter pylori lipopolysacchararide expresses Lewis x and/or y blood group
      antigens in mimicry with human gastric epithelial cells. Mimicry may have two
      diverging roles in pathogenesis. Infection may break tolerance and anti-Lewis
      antibodies may be induced that bind to gastric mucosa and cause damage. Secondly,
      mimicry may cause "invisibility" of the pathogen to the host, thus aiding
      persistence of infection. We demonstrate that Helicobacter pylori induces
      autoantibodies during infection. In orally infected pigs, these were specific for
      Lewis epitopes present on parietal cell H+K(+)-ATPase. In contrast, in infected
      patients the autoantibodies were directed to protein epitopes of H+K(+)-ATPase
      not induced through mimicry.

PMID- 10077750
TI  - Experimental model of Helicobacter pylori infection.
AB  - Critical issues in the development of a vaccine against Helicobacter pylori are
      represented by the definition of molecules important in the pathogenesis of the
      infection, by the availability of an animal model reproducing several aspects of
      the human infection, and lastly by the availability of powerful adjuvants
      allowing strong protection after mucosal delivery of the antigens. A mouse model
      of Helicobacter pylori infection was established in our laboratories. Vaccination
      of these animals with Helicobacter pylori antigens, such as VacA, CagA, etc.,
      induced protection, both prophylactic and therapeutic, when antigens were
      administered orally together with fully non toxic mutants of Escherichia coli
      heat-labile enterotoxin, as mucosal adjuvants. This experimental mouse model
      allows the study of the pathogenesis of Helicobacter pylori infection and the
      development of vaccines.

PMID- 10077751
TI  - Enterohepatic Helicobacters: natural and experimental models.
AB  - The genus Helicobacter now includes at least 18 formally named species as well as
      several novel helicobacters that have not been formally named. Eleven
      Helicobacter spp. colonize the intestinal tract of mammals and birds. In
      addition, a number of the intestinal helicobacters can colonize the biliary tract
      and liver, induce hepatitis and one in particular, Helicobacter hepaticus, can
      cause liver cancer in susceptible strains of mice. Further studies are needed to
      ascertain whether these helicobacters are also responsible for enterohepatic
      diseases in humans.

PMID- 10077752
TI  - Natural course of Helicobacter pylori gastric infection.
AB  - Helicobacter pylori acquisition induces chronic gastritis that affects antrum,
      corpus or both. In approximately half of the cases, Helicobacter pylori gastritis
      slowly (years, decades) develops to atrophic gastritis, thereby resulting in
      severe abnormalities in the function of the stomach. In humans, the appearance of
      intestinal metaplasia associates with atrophic gastritis (loss of normal antral
      and/or oxyntic glands), and intestinal metaplasia linearly increases in grade and
      extent with increasing age and progression of atrophy. Several mechanisms may
      play in role in the development of atrophic gastritis and intestinal metaplasia;
      i.e., including genetic liability of the host to destruction of cells and glands,
      specific cytotoxic strains of Helicobacter pylori, environmental factors other
      than the bacterial ones, and some functional properties of the stomach, such as
      output of acid and intragastric acidity. Atrophic and metaplastic alterations may
      also result from genotoxic and mutagenic injuries which are triggered by the
      inflammation, or are exogenous.

PMID- 10077753
TI  - Atrophy and atrophic gastritis: one step beyond the Sydney system.
AB  - An international workshop to evaluate the concepts of atrophy and atrophic
      gastritis was held in Houston in 1998. A consensus emerged that: 1) there is a
      phenotype of Helicobacter pylori-associated gastritis characterized by
      progressive loss of glands and intestinalization; 2) this phenotype is associated
      with increased risk of gastric ulcer and adenocarcinoma. This pattern must be
      consistently recognized are reproducibly diagnosed by histopathologists. The
      mucosal biopsy sampling suggested in the updated Sydney System were considered
      adequate to evaluate a patient for atrophic gastritis. Histopathologists were
      advised to refrain from making a diagnosis of "atrophic gastritis" unless
      moderate or severe unequivocal loss of gastric glands and/or moderate or severe
      metaplasia is found in at least 50% of the total gastric mucosa evaluated in the
      biopsy specimens. When atrophic or metaplastic changes appear to be more limited,
      "chronic gastritis with focal atrophy or metaplasia" should be diagnosed, and
      more extensive sampling should be obtained before the entity "atrophic gastritis"
      can be diagnosed. Particular attention was devoted to the issue of "unequivocal
      loss of gastric glands." In general, it was felt that it is difficult to be
      certain about loss of glands in the presence of moderate or severe inflammation,
      when one cannot be sure whether the glands have actually disappeared of have been
      displaced by the inflammatory infiltrate. In these circumstances, the term
      "indefinite for atrophy" can be used and the patient should be re-evaluated
      several months after the eradication of Helicobacter pylori infection.

PMID- 10077754
TI  - Epithelial cell turnover and apoptosis.
AB  - The homeostasis of gastric epithelial cells is maintained by the balance between
      cell proliferation and apoptosis. Alterations of these physiological cellular
      events in chronic pathological conditions of the stomach. As far as the
      proliferative pattern is concerned, an increase in the total number of epithelial
      proliferating cells and an abnormal distribution of the latter are frequently
      observed in chronic gastritis, gastric atrophy, intestinal metaplasia, gastric
      dysplasia and gastric cancer. Conversely, apoptosis has been found to be impaired
      in intestinal metaplasia, gastric dysplasia and cancer. Helicobacter pylori
      infection is associated with changes in epithelial-cell turnover, though their
      significance in gastric carcinogenesis is still controversial. An increase in
      overall epithelial cell proliferation and the upward shift of replicating cells
      toward the superficial part of the gastric pits are patterns usually observed
      during Helicobacter pylori infection and these changes can be reversed by
      successful eradication of the infection. However, it seems that this
      reversibility will be lost during progression through the steps of gastric
      carcinogenesis, such as intestinal metaplasia, probably representing the
      phenotypic expression of the true initiating phase of the carcinogenetic process.
      The influence of Helicobacter pylori infection on gastric epithelial apoptosis in
      humans is still controversial, since different results having been obtained by
      different authors. It seems that cagA status influences the effect of
      Helicobacter pylori on epithelial apoptosis, so that a different cagA make-up of
      the studied groups could explain these conflicting results. However, further
      studies are needed to elucidate this issue in humans.

PMID- 10077755
TI  - Routes of transmission of Helicobacter pylori infection.
AB  - Helicobacter pylori is an important gastroduodenal pathogen, which has been
      recognized as a Class I carcinogen factor for gastric cancer and gastric mucosa
      associated lymphoid tissue lymphomas. In spite of the world-wide spread of the
      infection, the route of transmission is still not known. We reviewed data from
      several sero-epidemiological studies and aimed to identify potential sources of
      Helicobacter pylori infection. Available evidence strongly suggests an inverse
      correlation between socio-economic status and prevalence of Helicobacter pylori.
      The infection is acquired mostly during childhood in the third world, but is rare
      in children in developed countries, where the prevalence of Helicobacter pylori
      increases with age. Following the detection of the bacterium in saliva, faeces,
      and gastric juice, oral-oral or faecal-oral transmission and iatrogenic spread,
      through the use of unsterile endoscopes, have been proposed as possible routes of
      infection. Helicobacter pylori has also been found in some domestic cats, but at
      present, the risk of infection from these animals appears slight. The mode of
      transmission of Helicobacter pylori, as is yet, not known. Available information
      support the hypothesis of spread through close personal contact, considering
      humans as the only significant reservoir of infection.

PMID- 10077756
TI  - Helicobacter pylori infection and dyspepsia.
AB  - Dyspepsia is defined as a persistent or recurrent pain or discomfort, localised
      in the upper abdomen, which may or may not be related to meals. Its prevalence in
      the general population is extraordinarily high (20-40%). Several pathological
      conditions can provoke dyspepsia, although non ulcer dyspepsia is the main cause.
      The relationships between Helicobacter pylori and non ulcer dyspepsia are
      discussed, namely the prevalence of Helicobacter pylori infection and the
      efficacy of its eradication in non ulcer dyspepsia. The management of dyspeptic
      patients in the community is analysed according to the Maastricht Consensus of
      1996. Our opinion is that, in Helicobacter pylori-positive dyspeptic patients,
      after a careful investigation with exclusion of other organic diseases, the
      bacterium should be eradicated.

PMID- 10077757
TI  - Gastro-oesophageal reflux and Helicobacter pylori.
AB  - The nature of the relationship between Helicobacter pylori infection and reflux
      oesophagitis is still not completely understood. To review the available evidence
      from the literature concerning the relationship between Helicobacter pylori
      infection and reflux oesophagitis with or without Barrett's metaplasia, we
      performed a Medline search to discover all published reports available in this
      field since the first description of Helicobacter pylori (1984) to April 1998. A
      total of 37 papers were found addressing the issue. From the available data, it
      can be concluded that Hp infection has probably only a minor protective role
      against the development of reflux oesophagitis. The related mechanisms are,
      however, still to be clarified. The presence of Helicobacter pylori infection is
      also likely to increase the efficacy of PPI drugs and, conversely, the
      eradication of the bacterium decreases the drug effect. The bacterial production
      of ammonia is the most likely factor explaining this observation. Furthermore, it
      is now sufficiently clear that patients placed on long-term PPI therapy develop
      atrophic gastritis only if Helicobacter pylori infection is not eradicated.
      Finally, both the development of metaplastic changes and the progression to
      severe dysplasia and adenocarcinoma in Barrett's oesophagus patients are
      phenomena not related to the presence of Helicobacter pylori antral or
      oesophageal colonization.

PMID- 10077758
TI  - Helicobacter pylori and gastric cancer.
AB  - Gastric cancer despite a declining incidence remains a significant cause of
      morbidity and mortality world wide. There is strong epidemiological and
      histological evidence to associate Helicobacter pylori infection with the
      subsequent development of gastric cancer. The exact pathophysiological mechanisms
      involved remain to be elucidated. There is evidence to relate Helicobacter pylori
      infection and subsequent inflammation with an increase in gastric epithelial cell
      proliferation and with the induction of apoptosis. Such alterations in cellular
      dynamics may promote the development of mitogenic cell lines by inducing DNA
      damage. Studies have shown that following successful treatment, proliferation
      rates return to normal. At what histological stage, eradication is of benefit is
      less clear. It is likely that following the development of atrophy or intestinal
      metaplasia eradication will only slow progression. It would, therefore, seem
      logical, that to establish any benefit for a population, treatment should be
      employed at an earlier stage. As yet, an at risk group has not been identified,
      and as such population screening cannot be advised, mainly as a result of
      financial implications and the risk of promoting the development of resistant
      strains. Recent studies have explored the rules of bacterial factors, CagA and
      VacA status, host factors, HLA type, and environmental factors as determinants of
      outcome. Results have been variable. The establishment of an at risk group would
      enable selective screening and treatment, and thus prevent the development of
      gastric carcinoma as a result of Helicobacter pylori infection in the long-term.

PMID- 10077759
TI  - Helicobacter pylori and lymphoproliferative disorders.
AB  - Primary gastric lymphoma of mucosa associated lymphoid tissue represent a
      distinct entity which is documented by their own histological classification. Our
      knowledge about all aspects of these lymphoma has substantially increased during
      the last few years. Epidemiological, histomorphological, molecular-biological and
      experimental data clearly underline that Helicobacter pylori infection of the
      gastric mucosa without doubt plays an important role both in the development and
      progression of MALT lymphoma. Considering histological malignancy (low grade and
      high grade lymphoma) and dissemination of the disease (stage) as decisive
      prognostic factors and therapeutical determinants, endoscopic bioptic diagnosis
      as well as endoscopic ultrasound are of major importance in establishing
      diagnosis and clinical stage. In the case of localized low grade lymphoma,
      eradication of Helicobacter pylori offers a promising therapeutic option.
      Surgical resection and radiochemotherapy have proven to be effective treatment
      modalities. There is a need for randomised trials to establish whether operative
      or conservative therapeutic strategies have to be favoured in the future.

PMID- 10077760
TI  - Helicobacter pylori infection and ischaemic heart disease.
AB  - Helicobacter pylori infection is probably one of the most widely spread
      infectious diseases in man and a growing body of knowledge provides evidence in
      favour of a causal link between this infection and the majority of upper
      gastrointestinal conditions. For example, we now know that peptic ulcer disease
      is an infectious disease; if the infection is diagnosed and treated, ulcer can be
      cured. On the other hand, in recent years, a number of epidemiological studies
      have focused on the possible relation between ischaemic heart disease and several
      infectious disorders, such as chronic dental infections, Cytomegalovirus,
      Coxsackie viruses, Chlamydia and, finally Helicobacter pylori. The results of
      studies on the association between ischaemic heart disease and Helicobacter
      pylori have, in particular, often been contradictory, and only some studies
      adjusted the results for confounding factors, and the adjustment of the results
      in some cases modified the association. In conclusion, even if coronary
      atherosclerosis may now be considered as an inflammatory process, according to
      several histologic and pathophysiologic studies, we cannot, for the moment, be
      sure that it is an infectious disease.

PMID- 10077761
TI  - Helicobacter pylori infection and vascular diseases.
AB  - Helicobacter pylori infection has recently been associated to some organic
      functional vascular disorders and, both observational and interventional studies
      have been carried out. A correlation between Helicobacter pylori infection and
      ischaemic heart disease was first described in 1994. Recent data, moreover,
      indicate a role of the bacterium in some functional vascular disorders such as
      primary headache and primary Raynaud phenomenon; indeed, some patients following
      eradication of Helicobacter pylori showed a significant improvement in the
      manifestations of these diseases. The host immune response against the bacterium
      may play an important role in the pathogenesis of vascular disorders, probably
      through a chronic stimulation of the release of vasoactive substances, such as
      cytokines, prostaglandins and others. However, various confounding factors such
      as co-infections, genetic and immunological host-factors, different strains of
      Helicobacter pylori or other may influence the data. Well designed case/control
      and randomized interventional studies are still needed to assess the real role of
      Helicobacter pylori in vascular disorders.

PMID- 10077762
TI  - Helicobacter pylori infection and autoimmune processes: an emerging field of
      study.
AB  - Evidence is accumulating that Helicobacter pylori infection may be closely
      associated with autoimmunity. However, whether autoimmunity plays a causal role
      in the pathogenesis of some of the diseases attributed to this bacterium or
      whether it is rather an epiphenomenon remains to be determined. In this brief
      review, a summary is made of current knowledge regarding the potential general
      mechanisms by which Helicobacter pylori causes mucosal damage. A review is then
      made of the evidence linking this bacterium to the production of different
      gastric autoantibodies. Finally, the reported association between Helicobacter
      pylori infection and some known autoimmune diseases is discussed. Although the
      data are still not sufficiently complete to draw definite conclusions,
      autoimmunity appears to be an important aspect of this infection and will
      certainly become a major field of study in the next few years.

PMID- 10077763
TI  - Diagnosis of Helicobacter pylori infection: non-invasive diagnostic tests.
AB  - The non-invasive urea breath test can demonstrate the presence of Helicobacter
      pylori infection with the same accuracy as invasive methods (histology, rapid
      urease test, culture), but with less distress and inconvenience to the patient.
      It is evident that this test can and should substitute invasive methods in
      patients with uncomplicated duodenal ulcer, in those with non-ulcer dyspepsia and
      in all who have gastrointestinal disorders that do not require endoscopic
      examination. The urea breath test has a primary role for determining the success
      of eradication therapy. It is ideal for short- and long-term follow-up,
      particularly in the case of duodenal ulcer, which is strictly related to the
      presence of Helicobacter pylori. In serious disease, when endoscopic examination
      is mandatory, such as complicated ulcer or mucose associated lymphoid tissue
      lymphoma, the urea breath test can still improve the diagnostic accuracy of
      Helicobacter pylori infection as it does not imply sampling error, to which
      biopsy is subject.

PMID- 10077764
TI  - Methodological problems and pitfalls of urea breath test.
AB  - Although several papers on the urea breath test have been published, some
      methodological questions are still unsolved: the dose of 13C-urea, the test meal
      composition, the breath sampling, the fasting or fed condition, the postural
      settings, and the cut-off points. Moreover, special conditions, such as those
      occurring in paediatric and uraemic patients or subjects with previous gastric
      surgery should be borne in mind when evaluating the 13C-urea breath test results.
      This review focuses on methodological problems and potential pitfalls which can
      affect the accuracy of the 13C-urea breath test.

PMID- 10077765
TI  - Diagnosis of Helicobacter pylori: invasive methods.
AB  - The methods which require endoscopy for the examination of the gastric mucosa are
      called invasive (direct) methods. Several tests can be performed on the gastric
      mucosa obtained by endoscopy: Rapid urease test, histology, smear (cytology),
      culture and polymerase chain reaction. A combination of at least two tests with
      high sensitivity and specificity is recommended for clinical trials, and, when
      possible, for clinical management of patients. In clinical practice the invasive
      methods should be carried out only in those patients to be treated with
      eradication regimes. All invasive methods rely on gastric biopsy samples.
      Therefore, the specimens should be taken under optimal conditions. Several
      factors guide the site and the number of biopsy specimens for identification of
      Helicobacter pylori infection. In pre-treatment diagnosis, the biopsies should be
      taken from the distal antrum (2 cm from the pylorus). The number required depends
      on the diagnostic method used: in Helicobacter pylori eradicated patients the
      same number of biopsies for histology and culture should be taken from the antrum
      and corpus. The sensitivity and specificity of the Rapid urease test varies from
      80-90% the results are known very quickly and the cost is very low. The maximal
      accuracy of histology is obtained with: an optimal specimen processing, an
      adequate staining and an experienced observer. This method of biopsy processing
      facilitates the identification of Helicobacter pylori which is commonly located
      on the superficial and foveolar epithelium. Sensitivity depends on the observer's
      experience and the extent of biopsy sampling. In general, the histological method
      has a sensitivity and specificity of 90-95%. In patients treated by proton pump
      inhibitors, antibiotics or bismuth salts two-four weeks prior to biopsy, the
      bacteria may be restricted to the corpus or fundus. Culture is strictly indicated
      in patients after failure of two or more eradication regimens to test for
      susceptibility and resistence. Specificity is 100% and sensitivity depends on the
      experience and interest of the microbiologist. The indication of polymerase chain
      reaction is only for research, specially, in molecular epidemiology and for
      fingerprinting.

PMID- 10077766
TI  - Atrophy, metaplasia and dysplasia: are they reversible?
AB  - The eradication of Helicobacter pylori results in the decrease and eventual
      disappearance of inflammation in the gastric mucosa. An important question with
      practical implications is whether treatment of H. pylori can promote the
      resolution of atrophy and intestinal metaplasia. If this happens, then one could
      infer that even in the presence of established multifocal atrophic gastritis the
      cure of Helicobacter pylori could reduce the risk of developing gastric cancer.
      Several investigators have addressed the issue, but the cumulative results remain
      inconclusive. The great latitude that there exists in the interpretation of the
      concept of atrophy and the patchy distribution of both atrophic changes and
      intestinal metaplasia (with resulting inevitable sampling error) are important
      reasons for the wide discrepancy in the conclusions reached by different authors.
      Controlled, long-term prospective studies conducted in different ethnic and
      geographic settings are needed to provide sound evidence-based answers to the
      question of reversibility of atrophy, intestinal metaplasia, and epithelial
      dysplasia.

PMID- 10077767
TI  - Eradication of Helicobacter pylori: why does it fail?
AB  - Currently, the first therapeutic attempt to eradicate Helicobacter pylori fails
      in one case out of six in intention to treat analysis. The main causes of failure
      are bad compliance, partly because of side effects that are severe in 1 to 4% of
      cases, absence of local validation of the treatment scheme, since some
      differences do exist between regions and countries, primary and secondary
      resistance of the strain (stable for Imidazole-derivates, but increasing for
      Macrolides), and, to a lesser extent, smoking and pre-treatment with proton pump
      inhibitors. Moreover, in routine medicine, inappropriate treatment cocktails are
      still prescribed, even by gastroenterologists. Obviously, there is a need for
      careful medical education and information both as far as concerns doctors and
      patients, for well-designed prescription, based on local experience and the
      precise previous history of every patient, as well as for continuous monitoring
      of the bacterial resistance to antibiotics. Culture of the strain is recommended
      after eradication failure with the classic one-week triple therapy, but if
      reliable culture and resistance testing are not available, the quadruple therapy
      as a second-line treatment is, so far, the best choice.

PMID- 10077768
TI  - Microbiological aspects of antibiotic resistant Helicobacter pylori strains.
AB  - Resistance of Helicobacter pylori to antibiotics has been described for
      macrolides, nitroimidizoles, and fluoroquinolones. In 1996, the mechanism of
      resistance to macrolides was determined to be a point mutation on the 23S rRNA
      which leads to decreased binding of macrolides to the ribosome. Recently,
      mutations in the gene coding for nitroreductase have been linked to resistance to
      nitroimidazoles but more work will be necessary to determine whether this is the
      only mechanism involved. Point mutations have also been associated with
      resistance to fluoroquinolones. A decreased susceptibility to amoxicillin has
      been observed and may be linked to changes in the penicillin binding proteins.
      The same phenotypic methods generally used to test antibiotic susceptibility can
      be applied to Helicobacter pylori. The disk diffusion method can be used for
      macrolides, the E-test for amoxicillin, and the point limit method for
      nitroimidazoles but the reference method of all of these is the agar dilution
      method. Molecular methods such as polymerase chain reaction-RFLP and various
      techniques using hybridization can also be employed but to date they have only
      been used for macrolides. These techniques have the advantage that they can be
      applied directly to the biopsy specimen.

PMID- 10077769
TI  - Novel therapeutic approaches to the management of Helicobacter pylori infection.
AB  - The eradication of Helicobacter pylori is indicated in a variety of conditions
      and the Maastricht consensus has recommended that first line regimens have an
      eradication rate of more than 80%. Present optimal first line therapy is proton
      pump inhibitor based triple therapy, but other regimens based on Ranitidine
      Bismuth Citrate may prove to be as effective, simple and well tolerated providing
      an alternative form of therapy. A variety of agents have been employed in various
      second line eradication regimens but no large scale trials have been conducted to
      establish the optimal second line regimen, following failure of standard line
      therapy. Novel antibiotics with activity against Helicobacter pylori are urgently
      required as resistance has developed to standard agents such as Clarithromycin
      and Metronidazole. Other agents such as the histamine receptor antagonist,
      Ebrotidine, and the proton pump inhibitor, Rabeprazole may have clinically
      important anti Helicobacter properties not merely related to their acid lowering
      effects. The ideal therapy would be safe effective vaccination but in the near
      future therapy is likely to be based on pharmacological agents taken orally.

PMID- 10077770
TI  - Development of a vaccine against Helicobacter pylori infection.
AB  - In animals, oral immunization can prevent or cure Helicobacter pylori infection,
      and prevent reinfection. Several antigens of the pathogen have been identified as
      protective antigens, and some appear to be well suited for use in an human
      vaccine. Initial clinical studies have shown that urease is safe in humans, and
      immunogenic in Helicobacter pylori-infected volunteers. The design of a
      protective vaccine in humans will probably depend upon the combination of two or
      more antigens, the identification of the optimal route of immunization, and the
      use of appropriate vaccine delivery systems. Because a vaccine against
      Helicobacter pylori is likely to be effective regardless of the mode of
      transmission of the infection, it represents a potential alternative to current
      therapies, with the added advantage of having a direct impact on the reservoir of
      the infection.

PMID- 10077771
TI  - [Diagnosis and treatment of systemic Candida infection in non-neutropenic
      patients].

PMID- 10077772
TI  - [In vitro susceptibilities of clinical isolates of coagulase-negative
      staphylococci to glycopeptide antibiotics].
AB  - Two hundred and thirteen clinical strains of coagulase-negative staphylococci
      isolated in Japan between 1980 and 1997 were analyzed for glycopeptide
      susceptibility by determining MIC using both Mueller-Hinton agar (MHA) and Brain
      Heart Infusion agar (BHIA) plates. Of 37 Staphylococcus epidermidis strains
      isolated between 1980 and 1981, all were susceptible to vancomycin and
      teicoplanin on both MHA and BHIA. However, of 122 isolates of Staphylococcus
      epidermidis isolated between 1994 and 1997, 1 (0.8%) was intermediate to
      vancomycin on MHA and 39 (32%) were intermediate on BHIA, while 3 (2.5%) and 27
      (22.1%) were intermediate or resistant to teicoplanin on MHA and BHIA,
      respectively. It was demonstrated that the susceptibilities of the strains in
      1990s to vancomycin and teicoplanin were significantly decreased compared with
      those in 1980s. Population analysis was performed with six strains each of
      Staphylococcus epidermidis and Staphylococcus haemolyticus (three with vancomycin
      MIC > or = 8 micrograms/ml and three with vancomycin MIC < or = 4 micrograms/ml
      using BHIA). The population curves of the Staphylococcus epidermidis strains
      showed a homogeneous pattern of susceptibility. Whereas, those for two
      Staphylococcus haemolyticus strains (vancomycin MIC = 8 micrograms/ml using BHIA)
      showed a typical heterogeneous pattern. Vancomycin-resistant mutants (MIC > or =
      32 micrograms/ml) were obtained with a high frequency of 10(-4)-(-5) from the
      strains by one-step selection with 16 micrograms/ml of vancomycin.

PMID- 10077773
TI  - [Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the
      treatment of elderly patients with pneumonia].
AB  - Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was
      compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the
      elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC
      3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days.
      1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No
      statistical differences were noted in the patients' backgrounds of either group.
      2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2%
      (17/23 cases). This was found to be statistically significant (Fisher's exact
      test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM)
      showed bacterial elimination. 4. No side effects were observed in the study. 5.
      Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and
      3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT,
      GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No
      statistical differences were noted in both groups. These results are consistent
      with SBT/ABPC as a highly effective antibiotic in the treatment of elderly
      patients with pneumonia.

PMID- 10077774
TI  - [Ecological treatment of bacterial vaginosis and vaginitis with Bio-three].
AB  - Ecological treatment of bacterial vaginosis and vaginitis with a Bio-three was
      studied, and the following results were obtained. 1. A total of 16 women with
      bacterial vaginosis and vaginitis were treated with intravaginal application of 2
      g of Bio-three (E. faecalis T-110, C. butyricum TO-A, B. mesentericus TO-A, pH
      6.9 +/- 0.3). The effect of the treatment was evaluated 3 days after
      administration by monitoring the vaginal discharge and bacteriological
      assessment. 2. The clinical improvement was evaluated and the decreases of
      vaginal discharge and vaginal redness were significant and vaginal pH was lowered
      significantly (5.29 +/- 0.24 vs. 4.31 +/- 0.37, p < 0.05). In the vaginal
      discharge 35 strains of bacteria were detected, but 3 days after administration,
      16/30 strains of Gram-positive bacteria, and 2 strains of Gram-negative bacteria
      disappeared. As for the overall bacteriological effects, 7/16 cases were
      eradicated, 1 case was partly eradicated, 6 cases were replaced. These findings
      indicated that the Bio-three therapy was effective in both clinical and
      bacteriological responses.

PMID- 10077775
TI  - [A consideration on the results of nationwide surveillance of antimicrobial
      susceptibilities--gram-positive cocci and gram-negative cocci].
AB  - The results of the semi-annual nationwide surveillance of antimicrobial
      susceptibilities, conducted by the Japanese Ministry of Health and Welfare during
      the period of January 1993 to July 1995, were analyzed for typical Gram-positive
      cocci and Gram-negative cocci in the purpose of provision of an index for
      antimicrobial selection. During these 3 years, Streptococcus pyogenes (group A)
      and Streptococcus agalactiae (group B) showed slightly increasing tendency in
      susceptibility to ofloxacin (OFLX) and sulfamethoxazole/trimethoprim (ST), while
      Streptococcus pneumoniae and Moraxella (Branhamella) catarrhalis showed slightly
      decreasing tendency to cefaclor (CCL). However, these annual changes were almost
      negligible. Generally, these microorganisms showed relatively good
      susceptibilities, every year, to the principal antimicrobial agents being
      approved for use against Gram-positive and -negative cocci. However,
      Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis
      showed tendencies of decreased susceptibility to some of the antimicrobial
      agents. On the other hand, cefmetazole (CMZ), vancomycin (VCM), latamoxef (LMOX),
      ST and minocycline (MINO) showed good activities against some of the Gram
      positive and -negative cocci to which no indication are approved. In conclusion,
      beside the identification of the causative microorganisms and the performance of
      antimicrobial susceptibility testing, such analyses (graphics of susceptibility
      tendency of clinical isolates to variety of antimicrobial agents) could be used
      as an index for selection of antimicrobial agents, when emergent and urgent
      selection of an antimicrobial agent is necessary.

PMID- 10077776
TI  - European Consensus Statement on Neonatal Hearing Screening. Finalised at the
      European Consensus Development Conference on Neonatal Hearing Screening 15-16 May
      1998, Milan.

PMID- 10077777
TI  - Ciprofloxacin versus cefuroxime axetil in the treatment of acute bacterial
      sinusitis. Sinusitis Infection Study Group.
AB  - OBJECTIVE: This study was conducted to compare the efficacy and safety of
      ciprofloxacin to cefuroxime axetil for the management of acute bacterial
      sinusitis or acute exacerbations of chronic sinusitis. METHOD: In this
      prospective, multicentre, randomized, double-blind clinical trial, 501 adult
      outpatients seen in 17 otolaryngology offices with both symptoms and radiographic
      evidence of acute maxillary sinusitis randomly received oral ciprofloxacin (500
      mg b.i.d.) or cefuroxime axetil (250 mg b.i.d.), each for 10 days. Patients were
      further subclassified as having either acute sinusitis or an acute exacerbation
      of chronic sinusitis. All patients underwent maxillary sinus aspiration at study
      entry to establish a microbiologic etiology. The primary measure of efficacy was
      the rate of clinical success in the efficacy-valid population at the end of
      therapy. Secondary measures included bacteriologic response at the end of
      therapy, and 2- to 4-week clinical and bacteriologic follow-up response rates in
      both efficacy-valid and intent-to-treat groups. RESULTS: Haemophilus influenzae
      (21%), Streptococcus pneumoniae (19%), Moraxella catarrhalis (14%), and
      Staphylococcus aureus (9%) were the most commonly isolated pathogens (target
      organisms) among the 225 causative organisms identified from 189 patients. Of 453
      adults valid for clinical efficacy (228 ciprofloxacin, 225 cefuroxime axetil),
      ciprofloxacin treatment was statistically equivalent to cefuroxime axetil at the
      end of treatment (87% vs. 83%; CI95 = -0.021 ... 0.106) and at follow-up (91% vs.
      88%; CI95 = -0.044 ... 0.080). The clinical response was similar for subgroups of
      patients with positive cultures, including the subset with target organisms.
      Bacteriologic eradication at end of therapy was similar between the two groups
      (97% ciprofloxacin, 95% cefuroxime axetil). Both treatments were equally well
      tolerated. CONCLUSION: Ciprofloxacin is as effective as cefuroxime axetil in the
      treatment of community-acquired acute sinusitis.

PMID- 10077778
TI  - Complete glottic closure during central apnea in lambs.
AB  - OBJECTIVE: The objectives of this study were threefold: to document complete
      glottic closure during artificially induced central apnea in lambs; to
      unequivocally confirm that thyroarytenoid muscle electrical activity during
      central apneas in lambs reflects complete glottic closure; and to evaluate the
      physiologic significance of this phenomenon in artificially induced central
      apneas in lambs. METHODS: We recorded thyroarytenoid (TA) muscle EMG, subglottic
      pressure, and lung volume simultaneously with direct endoscopic vision of the
      glottis from beneath on nine 11- to 15-day-old lambs during artificially induced
      central apneas. RESULTS: Thirty-eight central apneas were induced. Complete
      glottic closure was present on 35/38 (92%) of these apneas. Complete glottic
      closure was always paralleled by thyroarytenoid muscle electromyogram (EMG)
      activity (35/38). In no instance was TA EMG recorded without complete glottic
      closure. Moreover, positive subglottic pressure and maintenance of lung volume
      above functional residual capacity were observed in 27/30 (90%) and 18/19 (95%),
      respectively, of these apneas where complete glottic closure was present.
      CONCLUSIONS: Complete glottic closure is present throughout most artificially
      induced central apneas in lambs. Complete glottic closure is paralleled by TA EMG
      in artificially induced central apneas. Thyroarytenoid muscle electromyographic
      activity is a reliable way to document complete glottic closure during apneas,
      especially in the presence of positive subglottic pressure. These observations
      suggest that complete glottic closure could be a physiologic mechanism aimed at
      maintaining higher lung volumes to improve gas exchange during central apneas.

PMID- 10077779
TI  - Trends in hospital stay for five congenital malformations in the province of
      Quebec (1983-1995).
AB  - OBJECTIVE: The aim of this study was to examine the evolution of hospital stays
      and utilization of outpatient facilities for the treatment of five congenital
      malformations (choanal atresia, isolated cleft lip, isolated cleft palate,
      branchial cyst-sinus and thyroglossal duct cyst-sinus). METHOD: A retrospective
      review of MED-ECHO data for the province of Quebec from 1983 to 1995 was
      conducted. RESULTS: For three of the five studied malformations (cleft palate,
      branchial cyst-sinus, and thyroglossal duct cyst-sinus), there has been a trend
      toward reduced hospital stay and increased utilization of out-patient facilities.
      CONCLUSION: There has been a general tendency to reduce hospital stays even in
      procedures with potential airway and bleeding complications.

PMID- 10077780
TI  - Impact of clinical practice guidelines on clinicians' behaviour: tonsillectomy in
      children.
AB  - OBJECTIVE: This study was conducted to assess the extent to which developing and
      implementing clinical practice guidelines for listing children for tonsillectomy
      (with or without adenoidectomy) influenced the behaviour of participating ENT
      surgeons. METHOD: A before and after study in which the intervention (the
      development and dissemination of local practice guidelines) was introduced
      sequentially into different hospitals and surgical practice. The study was
      conducted in four ear, nose, and throat surgical services in the North of
      England, with 16 consultant ENT surgeons and their junior staff on 1190 children
      aged 0 to 14 years who were judged, prior to consultation with an ENT surgeon, to
      have been referred for throat-related problems for which tonsillectomy was one
      possible treatment option were included in the study. Decision reached by
      surgeons and proportion of decisions that complied with new guidelines. RESULTS:
      Of the clinical decisions to list children for tonsillectomy taken before
      introduction of locally agreed guidelines, 73% (486/660) conformed to the
      criteria in the subsequent guidelines, 15% (97/660) did not, and in 12% (77/660),
      it was impossible to judge. After the intervention, the corresponding figures
      were 73% (386/530), 14% (73/53), and 13% (71/530), respectively. When decisions
      were taken to break the guidelines, this was more often to list for tonsillectomy
      when it was not indicated--83% (141/170)--than to withhold tonsillectomy when it
      was indicated--17% (29/170). The aspects of guidelines that were breached in
      decisions to carry out tonsillectomy were: the age of the child was younger than
      the guidelines recommended--54% (75/141); there had been fever attacks of
      tonsillitis than the guidelines recommended--22% (32/141); and there were
      "significant" symptoms not included in the guidelines--20% (29/141). CONCLUSIONS:
      In spite of strong evidence to the contrary, local guidelines were formulated at
      a level that the majority of surgeons already attained. Guideline development and
      implementation, therefore, had very little impact on clinical practice. The
      process of local formulation of guidelines was not sufficient to achieve change
      toward evidence-based practice; clinical preference proved to be quite
      intractable. There is a need to enhance the ability of clinicians in the
      assessment and interpretation of research evidence. Previous work has emphasized
      the need to explore factors that influence clinical behaviour toward evidence
      based practice. Our study suggests the need for more research into why clinicians
      continue to follow clinical preference even when invited to base agreed local
      clinical policies on evidence.

PMID- 10077781
TI  - Otolaryngology in Atlantic Canada: practitioners' perspectives.
AB  - OBJECTIVE: A survey was conducted to assess practice conditions in Atlantic
      Canada for 1996. METHOD: Otolaryngologists in Nova Scotia, New Brunswick, Prince
      Edward Island, and Newfoundland/Labrador with at least 1 year of practice
      experience in the area were canvassed regarding general work concerns, office and
      OR waiting lists, income, support services, job satisfaction, future plans and
      personal recommendations for improvement. Nineteen of 40 surveyed responded
      (47.5%). RESULTS: The results revealed that Atlantic Canadians had to wait
      considerably longer than average Canadians for ENT services. This was
      particularly true for Nova Scotians who had to wait often more than double the
      national average. Forty-seven and a half percent of practitioners were
      dissatisfied with the practice climate, with many merely trying to maintain
      status quo. Increasing government constraints and budget cuts have led to
      practice protectionism and the loss of collegiality. There is little optimism for
      the future, with 42% predicting continued deterioration in the next 5 years. As a
      result, up to 58% are considering relocating elsewhere. CONCLUSION: Despite
      diminishing returns, these specialists continue to provide the best possible care
      for their patient patients--hoping for a better tomorrow.

PMID- 10077782
TI  - Musculocutaneous flap of the transverse nasalis muscle in repair of nasal-tip
      skin carcinoma.
AB  - OBJECTIVE: Reconstructing a nasal tip when there is neoplastic involvement is
      difficult, owing to the nature of the skin, which is thick, adhesive, and not
      very flexible, and to the proximity of the lower rim of the nasa ala, which must
      be respected. Dissection of twenty injected anatomic preparations has shown the
      reliability of using the vascular pedicle of the musculocutaneous flap of the
      transverse nasalis muscle. The technique was used in ten patients with skin
      carcinoma of the nasal tip. Esthetic results are excellent since the nasal ala is
      respected. A double-flap procedure may also be used for median defects.

PMID- 10077783
TI  - Consensus on ambulatory care among Quebec otolaryngologists.
AB  - OBJECTIVES: The aims of this study were to obtain consensus on the suitability
      (or nonsuitability) of outpatient facilities for 15 ENT surgical procedures, to
      identify the factors involved in the decision making, and to use the Delphi
      method to evaluate it for this purpose. METHOD: A prospective study of 26
      practising otolaryngologists in the Province of Quebec, using the Delphi method
      (3 rounds), was conducted. Fifteen adult and nine paediatric surgical procedures
      were included. RESULTS: Consensus (85% agreement) was obtained for eight
      procedures: septoplasty, rhinoplasty, endoscopic sinus surgery, otoplasty,
      mastotympanoplasty, lymph node biopsy, and branchial cyst excision (outpatient
      procedures) and tracheostomy (inpatient procedure). CONCLUSION: The Delphi method
      has been useful in initiating a process of rationalization about outpatient
      surgery.

PMID- 10077784
TI  - Cervicovertebral osteitis: a complication of uvulopalatopharyngoplasty with
      tonsillectomy.

PMID- 10077785
TI  - Congenital nasal pyriform aperture stenosis: a diagnostic clue to solitary
      maxillary central incisor prior to eruption in three infants.

PMID- 10077786
TI  - Laryngeal carcinoid tumours: report of three cases.

PMID- 10077787
TI  - Infection after rotator cuff repair.
AB  - Sixteen patients (15 men and 1 woman) were treated for infection complicating
      rotator cuff repair during the period 1975 through 1994. Eight of the 16 patients
      had their initial procedure performed elsewhere. The remaining 8 procedures were
      performed at our institution with the known incidence of this complication being
      0.27%. In addition to intravenous antibiotic therapy, an average of 3.5 (range 2
      to 8) operative procedures were required to eradicate the infections. Micro
      organisms cultured were Propionibacter in 6, coagulase negative Staphylococcus in
      4, Staphylococcus aureus in 4, Peptostreptococcus magnus in 1, and both
      Propionibacter and coagulase-negative Staphylococcus in 1. The deltoid was
      restored in all patients; the rotator cuff was reparable in 11. In the 12
      shoulders with greater than 1 year of follow-up (average 51 months, range 14 to
      165 months), active elevation averaged 110 degrees and external rotation 50
      degrees. Four patients had no pain, 4 had minimal pain, and the remaining 4 had
      moderate pain. Satisfactory final results, which were determined by the patients'
      opinion or with the use of either the University of California, Los Angeles score
      or the modified Neer system, were obtained in 5 (42%) of the shoulders.

PMID- 10077788
TI  - Anatomic relation between the medial collateral ligament of the elbow and the
      humero-ulnar joint axis.
AB  - The anatomic relation between the proximal attachment of the medial collateral
      ligament of the elbow joint and the humero-ulnar joint axis has not been clearly
      shown in a published study. We examined cadaveric specimens to find the exact
      relation between them. The medial collateral ligament was microscopically
      dissected to isolate specific fiber bundles. The length of each bundle was
      measured with a charge-coupled device camera system that faced the medial side of
      the elbow joint. The measurements indicated that the projected length of the deep
      middle bundle of the anterior oblique ligament, which is the strong cord-like
      part of the medial collateral ligament, is isometric during elbow flexion. The
      proximal end of the deep middle bundle was thus considered to be located almost
      on the humero-ulnar joint axis.

PMID- 10077789
TI  - Normal shoulder proprioception and the effect of lidocaine injection.
AB  - The purpose of this study was to investigate the effect of age, dominance, joint
      position, and lidocaine injection on proprioception of the normal shoulder.
      Position sense and the detection of passive shoulder motion were investigated in
      40 young (20 to 30 years) and old (50 to 70 years) subjects. An additional 20
      young subjects were tested before and after a glenohumeral (n = 10) or a
      subacromial (n = 10) lidocaine injection was performed. A significant decline
      occurred in proprioception between the young and old age groups. No difference
      was observed between dominant and nondominant sides. Position sense was
      consistently less accurate in the maximum range of motion tested when compared
      with the lesser ranges tested for flexion and abduction. No differences were
      identified in the ability to detect motion in flexion, abduction, and external
      rotation in the younger group, whereas in the older group a difference was
      observed in flexion. No learning effect was detected for any test trial. No
      significant changes occurred in proprioceptive ability after either glenohumeral
      or subacromial lidocaine injection was performed.

PMID- 10077790
TI  - The extraneural and intraneural arterial anatomy of the ulnar nerve at the elbow.
AB  - The purpose of this report was to investigate the vascular anatomy of the ulnar
      nerve at the elbow with a technique of combined India ink and latex injection
      followed by nondissection chemical debridement. Twenty-two fresh human cadaveric
      arms were injected with India ink to stain the intraneural microcirculation
      followed immediately by latex injection and chemical debridement for study of the
      extraneural vascularization. After clearing with a modified Spalteholtz
      technique, the intraneural blood supply was studied in 10 of the specimens. The
      findings demonstrated a consistent but segmental extraneural and intraneural
      vascular supply from the superior ulnar collateral, inferior ulnar collateral,
      and posterior ulnar recurrent arteries. No identifiable direct anastomosis was
      seen between the superior ulnar collateral and posterior ulnar recurrent arteries
      in 20 of 22 arms. The inferior ulnar collateral artery provided the only direct
      vascularization to the nerve in the region just proximal to the cubital tunnel.
      Although the clinical importance of maintaining specific arterial sources to the
      ulnar nerve has not been determined, these anatomic findings indicate that the
      arterial contribution from the inferior ulnar collateral artery may be more
      important than appreciated previously.

PMID- 10077791
TI  - Deltoid contracture: a radiographic survey of bone and joint abnormalities.
AB  - We performed a radiographic survey on 12 shoulders in 11 patients with a
      contracture of the deltoid present since childhood (juvenile) but left untreated
      until adulthood and on 14 shoulders in 10 patients with the same disorder first
      developed in adulthood (adult type). The greater tuberosity was located either
      under or near the acromion in all but 1 shoulder. Flattening of the humeral head,
      a high-positioned greater tuberosity, posterior rotation and vertical disposition
      of the acromion, inferior angulation of the lateral clavicle, and anterosuperior
      subluxation of the humeral head were noted in 58%, 33%, 75%, 67%, and 8% of the
      juvenile cases, respectively. Scoliosis and narrowing of the thoracic cage were
      each detected in 36% of the patients with juvenile deltoid contracture. Six of
      the juvenile cases were treated surgically and followed-up for a lengthy period.
      In these cases, however, the abnormalities persisted, except for subluxation of
      the humeral head and abnormal proximity of the acromion and greater tuberosity.
      In the adult-type cases no abnormalities were observed except for scoliosis in 4
      patients and anterosuperior subluxation of the humeral head in 1 shoulder. We
      conclude that treatment by surgical intervention should be performed at an age
      when spontaneous correction of the bone deformity can prevent future development
      of secondary arthrosis.

PMID- 10077792
TI  - Repair of massive rotator cuff tears in patients older than 70 years.
AB  - Major ruptures of the rotator cuff are common in elderly patients, and their
      management has been a challenge for orthopaedic surgeons. This study was
      undertaken to evaluate the results obtained in patients older than 70 years who
      were treated with open surgical repair for massive ruptures of the rotator cuff
      tendons and to correlate the functional outcomes with the quality of the repairs.
      Between January 1991 and November 1994, 69 patients older than 70 years of age
      underwent rotator cuff repairs of massive tears with a minimum follow-up of 2
      years (mean of 3 years). These patients were evaluated before and after surgery
      with the University of California at Los Angeles score. The mean age was 75 years
      (range 70 to 90 years), and female sex and right shoulder were predominant. A
      good bone-tendon repair was achieved in 55 patients, a fair bone-tendon repair in
      5 patients, a poor bone tendon-repair in 8 patients, and 1 patient had no repair.
      The mean University of California at Los Angeles rating score before surgery was
      9.4 points, and the mean postoperative score at final follow-up was 30.9 points,
      with an average improvement of 21.5 points (P = .0001). Satisfactory results were
      achieved in 78.2% of the patients (University of California at Los Angeles score
      equal or over 28). The patients' clinical results and postoperative arthrograms
      are evaluated with regard to the quality of cuff repair. Painful massive rotator
      cuff tears can be repaired in patients older than 70 years with satisfactory
      results.

PMID- 10077793
TI  - Effect of joint compression on inferior stability of the glenohumeral joint.
AB  - To determine the relative importance of negative intraarticular pressure,
      capsular tension, and joint compression on inferior stability of the glenohumeral
      joint we studied 17 fresh, normal adult cadaver shoulders using a "3 degrees of
      freedom" shoulder test apparatus. Translations were measured in intact and vented
      shoulders while a 50-N superior and inferior directed force was applied to the
      shoulder. Three different joint compressive loads (22 N, 111 N, 222 N) were
      applied externally. Tests were performed in 3 positions of humeral abduction in
      the scapular plane (0 degree, 45 degrees, 90 degrees) and in 3 positions of
      rotation (neutral, maximal internal, and maximal external). After tests of the
      intact and vented shoulder, the glenohumeral ligaments were sectioned and tests
      were repeated. With minimal joint compression of 22 N, negative intraarticular
      pressure and capsular tension limited translation of the humeral head on the
      glenoid. Increasing the joint compressive load to 111 N resulted in a reduction
      of mean inferior translation from 11.0 mm to 2.0 mm at 0 degree abduction, from
      21.5 mm to 1.4 mm at 45 degrees abduction, and from 4.5 mm to 1.2 mm at 90
      degrees abduction. With a compressive load of 111 N, venting the capsule or
      sectioning of glenohumeral ligaments had no effect on inferior stability.
      CLINICAL RELEVANCE: Glenohumeral joint compression through muscle contraction
      provides stability against inferior translation of the humeral head, and this
      effect is more important than negative intraarticular pressure or ligament
      tension.

PMID- 10077794
TI  - Recurrences after the open Bankart repair: a potential risk with use of suture
      anchors.
AB  - Eighty-seven consecutive patients were treated with an open Bankart repair for
      traumatic, recurrent anterior instability of the shoulder. Forty-six of these
      patients underwent a transosseous suture technique. Forty-one patients were
      operated on with suture anchors. After follow-ups that ranged from 18 to 85
      months, 7 of the 87 patients showed signs of recurrence and another 14 patients
      reported apprehension. Compared with the 66 patients without residual
      instability, these 21 patients were more likely to have been operated on with
      suture anchors (P < .05), had a greater incidence of hypermobility in joints
      other than the shoulder (P < .05), and had had a greater number of preoperative
      episodes (P < .05). In light of this data we recommend the transosseous suture
      technique for open Bankart repairs. In addition, a cautious and extensive
      capsular repair may be required when a patient reports frequent subluxations
      preoperatively or has hypermobility in some joints, if not in the shoulder per
      se.

PMID- 10077795
TI  - Comparison of magnetic resonance imaging and arthroscopy in the evaluation of
      shoulder pathology.
AB  - Fifty-seven subjects with shoulder pain, the cause of which was not clear on
      clinical examination, underwent magnetic resonance imaging (MRI) and arthroscopy.
      With arthroscopy as the standard of reference, the accuracy of MRI for diagnosing
      shoulder disease was assessed. Pathologic conditions were organized into 3
      groups: (1) labral tears, (2) rotator cuff disease, and (3) other pathologic
      conditions. At arthroscopic evaluation there were 15 labral tears, 24 rotator
      cuff tears, and 27 other abnormalities. MRI identified 11 of the labral injuries,
      with accuracy of 62%, sensitivity 73%, and specificity 58%. Rotator cuff tears
      were identified by MRI with accuracy of 68%, sensitivity 96%, and specificity
      49%. When partial rotator cuff tears were differentiated from complete tears,
      only 16 of 24 injuries were identified by MRI. Nonrotator cuff, nonlabral disease
      was identified with accuracy of 75%, sensitivity 63%, and specificity 87%. In our
      center MRI does not appear to be an accurate effective tool for assessing
      shoulder pathologic conditions in patients in whom the clinical picture is not
      clear and therefore may not be of assistance in surgical planning for patients
      with these difficult conditions.

PMID- 10077796
TI  - Aberrant muscle anterior to the shoulder joint: its clinical relevance.
AB  - Thirteen shoulders of 13 cases with aberrant muscle attached to the subscapularis
      encountered during surgery are described. The distal part of the subscapularis
      was completely or incompletely covered by aberrant muscle in all cases, and the
      anterior circumflex vessels were covered in 3 cases. Knowledge concerning these
      aberrant muscles is indispensable in minimizing confusion concerning surgical
      anatomy and in achieving adequate exposure of the shoulder during surgery while
      preserving the anterior circumflex artery, which constitutes the main nutrient
      vessel of the humeral head.

PMID- 10077797
TI  - Radiographic evaluation of glenohumeral kinematics: a muscle fatigue model.
AB  - The purpose of this study was to document the effect of muscle fatigue on
      glenohumeral kinematics. Twelve male volunteers without shoulder disease and with
      an average age of 27 years were studied. Glenohumeral anteroposterior radiographs
      were taken at 45 degrees intervals as the arm was abducted in the plane of the
      scapula from 0 degree to 135 degrees. This series of radiographs was performed
      both before and immediately after the subject performed a series of deltoid and
      rotator cuff fatiguing exercises. The average humeral head position or
      translation before and after muscle fatigue for each arm angle was compared. For
      all subjects, before fatigue, the position of the humeral head was below the
      center of the glenoid for all angles of abduction. There was essentially no
      change in position of the humeral head in the prefatigue state, as the arm was
      abducted from 0 degree to 135 degrees with no more than an average 0.3 mm of
      total humeral head excursion. After fatigue, excursion of the humeral head
      increased to an average of 2.5 mm between the tested positions. The position of
      the humeral head with the arm at 0 degree of abduction was lower or had migrated
      inferiorly compared with the rested state, with an average 1.2 mm significant
      increase in inferior translation. With the initiation of abduction, the humeral
      head demonstrated significant superior migration or translation in all positions
      tested. This result has important implications for conservative treatment of
      shoulder impingement and underscores the importance of rehabilitation to maximize
      the endurance and strength of the rotator cuff musculature.

PMID- 10077798
TI  - Arthroscopic partial resection of the scapula for snapping scapula: a new
      technique.
AB  - We describe a new method of arthroscopic bony surgery to the superomedial corner
      of the scapula in patients with painful snapping caused by bony impingement.
      Seven patients who had failed conservative treatment were monitored
      prospectively. In 5 patients we used 3-dimensional computed tomography as a
      diagnostic aid. The condition was successfully managed in 6 cases. One procedure
      was abandoned because of intraoperative swelling; there was 1 minor wound
      infection. In all cases the operation relieved symptoms. Two of the 5 patients
      scanned had narrowing of the superomedial interval. The advantages of this
      technique are in cosmesis and early rehabilitation, and the early results are
      good. Provided due care is taken in portal placement, complications should be
      minimal. Three-dimensional reconstruction computed tomography scanning may be
      useful in some patients to show narrowing between the superomedial corner and the
      chest wall, but we cannot at present recommend its routine use.

PMID- 10077799
TI  - Revision shoulder stabilization: 2- to 10-year results.
AB  - We evaluated 43 patients who underwent revision shoulder stabilization between
      1978 and 1992. Twenty-three shoulders in 23 patients had unidirectional anterior
      shoulder instability (group A), whereas 21 shoulders in 20 patients exhibited
      multiple directions of shoulder instability (group B). Within group A recurrent
      instability developed at a mean of 35.5 months after the initial stabilization.
      Recurrence was traumatic in 12 patients. Revision surgery included a Bankart
      repair in 19 patients (coupled with capsular shift in 15 and a Bristow in 1) and
      capsular shift alone in 4. Within group B recurrent instability developed at a
      mean of only 16 months after the initial stabilization and was traumatic in only
      2 patients. Revision surgery included capsular shift in 11 patients, Bankart
      repair in 5, anterior/posterior graft reconstruction in 3, and posterior bone
      block in 2. All patients had significant capsular laxity. A Bankart lesion was
      found in only 24% of patients. The mean follow-up from revision was 77.3 months
      (range 24 to 196 months) in group A. The results were excellent in 8 patients,
      good in 7, fair in 4, and poor in 4. Three of the 4 failures, however, had
      undergone successful reoperation before follow-up, improving the number of good
      or excellent results to 18 (78%). In contrast, at a mean follow-up of 61.5
      months, only 9 (39%) good or excellent results occurred in group B despite
      multiple reoperations. Four patients ultimately went on to have glenohumeral
      fusion. Revision shoulder stabilization is a reliable procedure for patients who
      have recurrent anterior instability; however, it is unpredictable in patients who
      have multidirectional instability, with surgical failure and reoperation
      occurring frequently.

PMID- 10077800
TI  - Evolution of lesions of the labrum-ligament complex in posttraumatic anterior
      shoulder instability: a prospective study.
AB  - The aim of this study was to evaluate the evolution of intraarticular disease in
      posttraumatic shoulder instability. Ninety-one patients with posttraumatic
      shoulder instability were examined arthroscopically. The intraarticular disease
      was recorded on a special documentation sheet (containing 67 descriptive items).
      The patients were divided into 5 subgroups: first-time dislocation (n = 9); first
      or second recurrence (n = 12); 3 to 5 recurrences (n = 23); 6 or more recurrences
      (n = 32); and chronic subluxations (n = 15). All data were examined
      statistically. Each lesion was correlated with stage of evolution, age, and
      number of recurrences. The most frequent lesions were regrouped into "lesion
      families." The initial and most constant lesion was the periosteal disinsertion
      of the anteroinferior labrum (single lesion). The labral detachment was succeeded
      in a second stage by the disinsertion of the glenohumeral ligament complex
      (double lesion). With additional recurrences, stress mechanisms altered the
      detached structures through tissue damage (triple lesion). The fourth stage saw
      the extension of the degenerative process, which led to failure at the insertion
      site and destruction of the labrum-ligament complex (quadruple lesion). This
      study reveals that recurrences progressively damage stabilizing structures. A
      pathophysiological classification into 4 stages is proposed, however, that would
      permit a precise therapeutic strategy for arthroscopic shoulder stabilization.

PMID- 10077801
TI  - Use of botulinum A toxin in irreducible shoulder dislocation caused by spasm of
      pectoralis major.

PMID- 10077802
TI  - Erosion and nonunion of the first rib after sternoclavicular reconstruction with
      Dacron.

PMID- 10077803
TI  - Bilateral osteochondromatosis of the subacromial bursae with incomplete rotator
      cuff tears.

PMID- 10077804
TI  - Dissociation of the glenoid component in cementless total shoulder arthroplasty.

PMID- 10077805
TI  - Complex fractures of the distal humerus and their complications.

PMID- 10077806
TI  - Osteoid osteoma of the clavicle.

PMID- 10077807
TI  - [In vitro assessment of semen for the prediction of fertility].
AB  - The prediction of fertility is a primary goal in the field of reproductive
      medicine. The aim of the present paper is to describe the value of conventional
      and modern sperm analysis systems considering the process of fertilization. The
      classical assessment of motility and morphology enables the rough estimation of
      semen quality in order to select ejaculates for the use in artificial
      insemination. Recent methods for sperm diagnosis, such as fluorescent marking for
      the detection of sperm plasma membrane integrity, the hypoosmotic swelling test,
      and computer assisted semen analysis allow for the evaluation of a large number
      of spermatozoa and the assessment of sperm dynamics under in vitro-fertilization
      conditions. The oocyte penetration test investigates the ability of spermatozoa
      for capacitation, hyperactivation and acrosome reaction in vitro. The amount of
      specific seminal plasma proteins is related to fertility and thereby provides an
      additional semen evaluation method. For the use of a given semen test the
      specific in vitro condition has to be considered. In addition, the evaluated
      criteria relevant for the process of fertilization need to be defined. The
      combination of selected semen tests gives a higher accuracy for the prediction of
      fertilizing capacity compared with a single test.

PMID- 10077808
TI  - [Case report. Urinary incontinence in a newborn foal].

PMID- 10077809
TI  - [Experiences with an Internet-based lecture script on animal obstetrics].
AB  - An internet based lecture script was developed on animal obstetrics to enhance
      the traditional lecture. The script summarizes the manuscript of the lecturer and
      contains additional information and reading materials. The script has
      approximately 600 pages and shows 400 slides, graphs and animations. Students'
      perception was surveyed by means of a questionnaire. 152 of 201 students (75.6%)
      in the 3rd and 5th year participated in the survey. Overall, the script was rated
      1.9 on a 5-point scale (1 = excellent, 5 = poor). Our experiences with the
      internet based script were primarily positive. However, the curriculum of the
      veterinary education and technical prerequisites will effect the long-term
      success of such systems.

PMID- 10077810
TI  - [Effect of a 10 day postpartum administration of a PGF2 alpha analog at different
      concentrations on the course of the puerperium and fertility in dairy cows].
AB  - In this double-blind Study 72 dairy cows were treated with injections of
      Luprostiol (Reprodin). 32 cows served as control. Gynaecological examinations in
      10-day intervals up to day 40 post partum and determination of progesterone
      levels in milk samples taken in 3-day intervals up to day 73 p. p. were
      performed. The administration of PGF2 alpha did not improve the early onset of
      ovarian activity in cows with uncomplicated or complicated delivery. Ovaries
      without detectable function up to day 73 p. p. only occurred in the placebo
      group, representing a significant (p < 0.05) difference to the control group. In
      cows after uncomplicated as well as in animals after complicated delivery
      involution of the uterus up to day 20 p. p. progressed faster in the verum group
      compared to the control group. Cervical diameters were highest in the placebo
      group up to day 20 p. p. Until day 40 p. p. the cervical diameters of the
      probands equaled those of the control animals. In contrary to cows after
      uncomplicated delivery the injection of PGF2 alpha after complicated parturition
      lead to a significant (p < 0.05) reduction of puerperal endometritis. Neither in
      cows with uncomplicated nor complicated delivery the administration of PGF2 alpha
      resulted in an improved conception rate. There were no significant positive
      effects on fertility parameters to be detected in general. Partial results
      observed were not dose dependent.

PMID- 10077811
TI  - [Therapeutic and prophylactic effect of LH-release in cattle].
AB  - In this study, LH release in response to the GnRH agonist buserelin and during
      treatment with a progesterone-releasing intravaginal device (PRID) was studied. A
      dose of 20 micrograms buserelin induced a more pronounced LH release than 4, 8,
      40 and 80 micrograms. After injection of buserelin, pituitary response to a
      second buserelin injection was markedly reduced for at least 24 hours. Repeated
      buserelin injections at an interval of several hours therefore cannot be
      recommended. LH release was markedly suppressed by treatment with PRID. Two PRID
      tended to be more effective than one. After PRID removal, LH release increased
      significantly.

PMID- 10077812
TI  - [Postpartum anestrus in dairy cattle--a review].
AB  - In modern high-yielding dairy herds fertility is of major economic importance. In
      order to gain maximum profit, calving intervals should not exceed 365 days. The
      achievement of a 365-day calving interval requires an early resumption of ovarian
      activity, an excellent oestrus detection, and a high first-service conception
      rate. Especially the inability to detect oestrus and to mate the cows by 60 to 80
      days after calving is a common problem among dairy farmers nowadays. In this
      article a review is given about the occurrence, causes, treatment and prevention
      of post-partum anoestrus in dairy cows.

PMID- 10077813
TI  - [Feasibility of detecting steroid hormones in cattle feces for monitoring ovarian
      function].
AB  - Faecal material from four non pregnant cows was withdrawn in two-day intervalls
      during a four-week period. At the same time bloodsamples were taken to monitor
      the ovarian function. Clinical and ultrasonographical examinations were recorded
      in parallel. To look for the stability of the faecal steroid analogues for P4
      (Progesterone) and E2 (Estradiol-17 beta) faecal material was stored at 37
      degrees C and samples from that analyzed in two-day intervals. The P4
      (Progesterone)-analogues values in the faeces showed good correlation to cycling
      ovarian functions as monitored by bloodlevels from P4, clinical examination and
      ultrasonography. In contrast the E2-analogues values showed no cycling pattern.
      One cow however showed ovarian cysts which was monitored in the P4 values for
      blood and faeces. Concerning the stability of the steroid analogues it could be
      demonstrated that the P4-values show a steady decrease with minimum values of 20
      ng/g dry material. During the first four days after sampling reliable values for
      clinical interpretations can be found. The concentrations for E2 are very
      inconstant and so far not of interest. The investigation shows that the faecal
      steroid P4 can be used for monitoring ovarian function. It has to be analyzed
      within four days after sampling when stored at room temperature.

PMID- 10077814
TI  - [Brucellosis and Aujeszky's disease in a wild boar enclose. Case report].
AB  - In wild boars kept in a paddock of approximately 1.7 square miles Brucella suis
      biotype 2 was isolated and Aujeszky's disease was diagnosed by serological tests.
      To clear the paddock, the wild boars were lured by offered food and caught using
      specially built smaller pens. They were then transported to a location far off
      their original surroundings and euthanized. Of a total of 297 wild boars kept in
      the paddock, 71% were caught and 28% shot. Three wild boars (= 1%) were found
      trapped. The described method could also be used in case of epidemics to catch
      wild boars living outside existing paddocks. In order to avoid killing the boars
      which stayed in separate quarantine enclosures, a darting gun was used to
      anaesthetize the animals with tiletamine/zolazepam. Achieved sedation levels were
      deep enough to allow for blood samples to be taken from the jugular vein without
      any problems, i.e. without any defence reactions of the boars. The origin of
      infection could not be identified.

PMID- 10077815
TI  - [Follicular dynamics after treatment with hCG for ovulation induction in mares].
AB  - In this study the use of hCG for induction of ovulation is described. Factors
      such as follicle diameter at the time of administration of hCG (3000 IE hCG
      i.v.), follicular growth after hCG and the rate of double ovulations were
      evaluated. A total of 168 mares presented for artificial insemination were used.
      In 249 estrous periods hCG was given to mares exhibiting standing estrous when a
      minimum follicle diameter of 30 mm and a well developed edema of the endometrium
      could be detected by ultrasonography. In nine estrous periods ovulation occurred
      within 24 hours after hCG. The majority of mares (216; 86.7%) ovulated 24 to 48
      hours after hCG and in 24 cases ovulation was delayed beyond 48 hours. Follicle
      size at the time of hCG administration (30-34 mm, 35-39 mm, > or = 40 mm) had no
      influence on the percentage of mares ovulating 24 to 48 hours after hCG (89.2%,
      87.9%, and 83.7%, respectively). Double ovulations could be observed in 17.7% of
      estrous periods. The one cycle pregnancy rate was not influenced by follicle size
      (small 45.9%; medium 41.6%; large 47.5%). Repeated treatments with hCG during
      successive estrous cycles within one year did not influence the rate of
      responding to hCG. Mares in standing estrous respond well to hCG if a minimum
      follicle size of 30 mm and a well developed endometrial folding is present.

PMID- 10077816
TI  - [Effect of the administration of PGF2 alpha synchronously with insemination on
      the pregnancy rate in mares in an insemination program].
AB  - Investigations in different species including the horse have demonstrated that
      prostaglandin F2 alpha (PGF2 alpha) is involved in initiating uterine
      contractions occurring during mating and artificial insemination (A.I.). Uterine
      contractions play an important role with respect to the sperm transport within
      the female genital tract. The objective of the present investigation was to
      evaluate whether the administration of PGF2 alpha (Dinoprost) synchronously to
      A.I. could have a positive effect on the pregnancy rate in mares. A field study
      including 346 warmblood-mares (age two to 20 years) belonging to a private
      studfarm was conducted during the breeding season 1996. The mares were assigned
      to two groups, group A: mares with spontaneous ovulation, group B: mares in which
      the ovulation was induced by a GnRH-analog-implant (Deslorelin). PGF2 alpha
      (Dinoprost) was administered either intramusculary (i.m., 5.0 mg) or intrauterine
      (i.ut., 0.5 mg diluted in 1.9 ml isotonic NaCl-solution and added to the semen
      dosis). The study was carried out in a double-blind fashion using isotonic NaCl
      solution as a placebo. The mares of each group were randomly assigned to one of
      the two treatments (i.m. vs. i.ut.). The following first cycle pregnancy rates
      (day 18) were obtained in mares treated and inseminated once per oestrus: group
      A1 (PGF2 alpha, i.m.): 54.5% (n = 33); group A2 (placebo, i.m.): 69.7% (n = 33);
      group A3 (PGF2 alpha, i.ut.): 65.4% (n = 26); group A4 (placebo, i.ut.): 69.8% (n
      = 32); group B1 (PGF2 alpha, i.m.): 56.5% (n = 46); group B2 (placebo, i.m.):
      29.6% (n = 27); group B3 (PGF2 alpha, i.ut.): 66.7% (n = 45); group B4 (placebo,
      i.ut.): 60.0% (n = 30). The pregnancy rates did not differ between the different
      groups with the exception of group B2 (p < 0.05). In mares treated repeatedly
      during the oestrus period (group A, n = 88; group B, n = 23), the pregnancy rates
      did not differ significantly between treatment and control groups. From the
      results obtained it is concluded that the PGF2 alpha-application did not show an
      effect on the pregnancy rate. Further factors influencing the results to a small
      degree were the stallions, semen age and quality and frequency of insemination
      per oestrus.

PMID- 10077817
TI  - [Veterinary recommendations for the handling of equine virus arteritis (EVA) in
      practical breeding care].
AB  - The equine virus arteritis (EVA) consistently epidemically varying throughout the
      different breeds of the horse breeding countries is up to now only of lower
      significance by means of the typical clinical manifestation as well as an
      abortion causing factor. The susceptibility of the sexual mature stallions
      against the equine arteritis virus (EAV) causes different infection response
      which may lead to some restrictions in their use in natural breeding especially
      in the artificial insemination. In a certain not precisely predictable part of
      the stallion population EAV infection will cause a transient or permanent virus
      presence in the accessorial apparatus of the genital tract with transient or
      permanent shedding of the virus via seminal secretions. This makes the stallion
      to one of the dominant factors of the propagation of the field virus. The use of
      EAV shedding stallions in natural breeding or AI is very risky and only
      justifiable under certain precautions and additional measurements e.g. in EAV
      seropositive or vaccinated mares. A consistent progress in the defeat of the
      disease can be expected from vaccination of the seronegative stallions with dead
      or inactivated live vaccines as they are considered to be able to prevent the
      establishing of EAV shedder status.

PMID- 10077818
TI  - Bacterial catabolic transposons.
AB  - The introduction of foreign organic hydrocarbons into the environment in recent
      years, as in the widespread use of antibiotics, has resulted in the evolution of
      novel adaptive mechanisms by bacteria for the biodegradation of the organic
      pollutants. Plasmids have been implicated in the catabolism of many of these
      complex xenobiotics. The catabolic genes are prone to undergo genetic
      rearrangement and this is due to their presence on transposons or their
      association with transposable elements. Most of the catabolic transposons have
      structural features of the class I (composite) elements. These include
      transposons for chlorobenzoate (Tn5271), chlorobenzene (Tn5280), the newly
      discovered benzene catabolic transposon (Tn5542), and transposons encoding
      halogenated alkanoates and nylon-oligomer-degradative genes. Transposons for the
      catabolism of toluene (Tn4651, Tn4653, Tn4656) and naphthalene (Tn4655) belong to
      class II (Tn3 family) elements. Many catabolic genes have been associated with
      insertion sequences, which suggests that these gene clusters could be rapidly
      disseminated among the bacterial populations. This greatly expands the substrate
      range of the microorganisms in the environment and aids the evolution of new and
      novel degradative pathways. This enhanced metabolic versatility can be exploited
      for and is believed to play a major part in the bioremediation of polluted
      environments.

PMID- 10077819
TI  - Rhamnose lipids--biosynthesis, microbial production and application potential.
AB  - Biosurfactants containing rhamnose and beta-hydroxydecanoic acid and called
      rhamnolipids are reviewed with respect to microbial producers, their
      physiological role, biosynthesis and genetics, and especially their microbial
      overproduction, physicochemical properties and potential applications. With
      Pseudomonas species, more than 100 g l-1 rhamnolipids were produced from 160 g l
      1 soybean oil at a volumetric productivity of 0.4 g l-1 h-1. The individual
      rhamnolipids are able to lower the surface tension of water from 72 mN m-1 to 25
      30 mN m-1 at concentrations of 10-200 mg l-1. After initial testing, rhamnolipids
      seem to have potential applications in combating marine oil pollution, removing
      oil from sand and in combating zoosporic phytopathogens. Rhamnolipids are also a
      source of L-rhamnose, which is already used for the industrial production of high
      quality flavor components.

PMID- 10077820
TI  - Production of sophorolipids from whey: development of a two-stage process with
      Cryptococcus curvatus ATCC 20509 and Candida bombicola ATCC 22214 using
      deproteinized whey concentrates as substrates.
AB  - In order to produce sophorolipids from whey, thereby lowering the lactose content
      and biological oxygen demand, a two-step batch cultivation process was developed
      including medium sterilization by filtration. In the first step, whey was
      sterilized by a combination of crossflow and sterile filtration. Because the
      sophorolipid-producing yeast Candida bombicola ATCC 22214 was not able to use
      lactose as a carbon source directly, the oleaginous yeast Cryptococcus curvatus
      ATCC 20509 was grown on deproteinized whey concentrates (DWC). With 1:1 diluted
      DWC-20, lactose was consumed as the carbon source and biomass (24 g/l dry weight
      content) as well as single-cell oil (SCO, 10 g/l) were produced. The cultivation
      broth was disrupted with a glass bead mill and it served as medium for growth (29
      g cell dry mass/l) and sophorolipid production (12 g/l) of the yeast C.
      bombicola.

PMID- 10077821
TI  - Development of an arming yeast strain for efficient utilization of starch by co
      display of sequential amylolytic enzymes on the cell surface.
AB  - The construction of a whole-cell biocatalyst with its sequential reaction has
      been performed by the genetic immobilization of two amylolytic enzymes on the
      yeast cell surface. A recombinant strain of Saccharomyces cerevisiae that
      displays glucoamylase and alpha-amylase on its cell surface was constructed and
      its starch-utilizing ability was evaluated. The gene encoding Rhizopus oryzae
      glucoamylase, with its own secretion signal peptide, and a truncated fragment of
      the alpha-amylase gene from Bacillus stearothermophilus with the prepro secretion
      signal sequence of the yeast alpha factor, respectively, were fused with the gene
      encoding the C-terminal half of the yeast alpha-agglutinin. The constructed
      fusion genes were introduced into the different loci of chromosomes of S.
      cerevisiae and expressed under the control of the glyceraldehyde-3-phosphate
      dehydrogenase promoter. The glucoamylase and alpha-amylase activities were not
      detected in the culture medium, but in the cell pellet fraction. The transformant
      strain co-displaying glucoamylase and alpha-amylase could grow faster on starch
      as the sole carbon source than the transformant strain displaying only
      glucoamylase.

PMID- 10077822
TI  - The expression signals of the Lactobacillus brevis slpA gene direct efficient
      heterologous protein production in lactic acid bacteria.
AB  - A cassette based on the expression signals of the Lactobacillus brevis surface
      (S)-layer protein gene (slpA) was constructed. The low-copy-number vector
      pKTH2095, derived from pGK12, was used as the cloning vector. The efficiency of
      slpA promoters in intracellular protein production was studied using three
      reporter genes, beta-glucuronidase (gusA), luciferase (luc) and aminopeptidase N
      (pepN) in three different lactic acid bacteria hosts: Lactococcus lactis,
      Lactobacillus plantarum and Lactobacillus gasseri. The S-layer promoters were
      recognized in each strain and especially L. lactis and Lb. plantarum exhibited
      high levels of transcripts. The production kinetics of reporter proteins was
      studied as a function of growth. The GusA, Luc and PepN activities varied
      considerably among the lactic acid bacterial strains studied. The highest levels
      of beta-glucuronidase and luciferase activity were obtained in L. lactis. The
      level of GusA obtained in L. lactis corresponded to over 15% of the total
      cellular proteins. The highest level of aminopeptidase N activity was achieved in
      Lb. plantarum where PepN corresponded up to 28% of the total cellular proteins at
      the late exponential phase of growth. This level of PepN activity is 30-fold
      higher than that in Lb. helveticus, which is the species from which the pepN gene
      originates.

PMID- 10077823
TI  - Efficient expression of mosquito-larvicidal proteins in a gram-negative bacterium
      capable of recolonization in the guts of Anopheles dirus larva.
AB  - The gram-negative bacterium, An11/2 G1, isolated from the guts of Anopheles dirus
      mosquito larvae, was identified as Enterobacter amnigenus. The E. amnigenus was
      able to recolonize in the gut of An. dirus larva but not in those of Aedes
      aegypti and Culex quinquefasciatus larvae. It was able to float in water for a
      longer period than Bacillus thuringiensis subsp. israelensis and Bacillus
      sphaericus. These are desirable characteristics for a delivery vehicle of
      mosquito-larvicidal toxins for the control of mosquito larvae, and E. amnigenus
      was therefore used as a host to express the cryIVB gene of B. thuringiensis
      subsp. israelensis and the binary toxin genes of B. sphaericus. The recombinant
      E. amnigenus produced a high level of CryIVB protein, which was toxic to larvae
      of Ae. aegypti and An. dirus. Another E. amnigenus producing the 51-kDa protein
      of B. sphaericus was toxic to larvae of An. dirus and Cx. quinquefasciatus. The
      recombinant plasmids were stable in E. amnigenus without the presence of
      selective pressure for at least 23 generations. The recombinant E. amnigenus
      should represent a desirable biological agent for controlling mosquito larvae.

PMID- 10077824
TI  - A novel mutation, of the Bacillus subtilis hut operon that relieves both
      catabolite repression and amino acid repression.
AB  - A mutation, designated hutCR11, which resulted in high expression of the hut
      operon and release of the catabolite repression and amino-acid repression of hut
      expression, was isolated and determined to be a T-to-G transversion at position
      +30 (+1 indicates the transcription-initiation site). In the hutCR11 mutant,
      levels of hutP mRNA were 5-fold higher than those in wild-type cells under
      conditions of non-induction and induction and 11-fold higher under conditions of
      catabolite repression and amino-acid repression. Mutation analysis showed that
      two types of base change (T-->A and T-->C) at position +30 did not cause high
      expression of the hut operon, indicating that this was specifically caused by the
      single base substitution (T-->G) at position +30. The base substitution of A for
      T at position +30 also led to partial relief of both catabolite repression and
      amino-acid repression. These results indicate that the nucleotide sequence at +30
      is important for regulation of both catabolite repression and amino-acid
      repression of the hut operon.

PMID- 10077825
TI  - Correlation between polymerase chain reaction analysis of the histidine
      biosynthesis operon, randomly amplified polymorphic DNA analysis and phenotypic
      characterization of dairy Lactococcus isolates.
AB  - A collection of 32 lactococcal strains isolated from raw milk in the Camembert
      RDO (registered designation of origin) area were phenotypically and genotypically
      characterized. As expected for environmental isolates, all strains had a
      Lactococcus lactis subsp. lactis phenotype. The strains were then genotypically
      identified by the randomly amplified polymorphic DNA (RAPD) technique, using
      reference strains of lactococci. Two major clusters were identified containing
      the two subspecies lactis and cremoris. The subspecies lactis cluster could be
      divided into five subgroups whereas there was a high coefficient of similarity
      between all strains in the subspecies cremoris cluster. This RAPD classification
      was then compared with that of a traditional PCR assay using L. lactis species
      specific primers corresponding to part of the histidine biosynthesis operon. The
      two subspecies were differentiated by the size of the fragment amplified (about
      200 bp longer for subspecies cremoris). Unlike preliminary phenotypic
      assignments, the results of PCR experiments corroborated the genotypic
      identification of the lactococcal strains by RAPD allowing the technique to be
      reconsidered on the basis of its taxonomic efficiency.

PMID- 10077826
TI  - Bioavailability of hydrocarbons during microbial remediation of a sandy soil.
AB  - The microbial degradation of hydrocarbons was studied in an artificially
      contaminated sandy soil, using a pilot-scale percolator system. After a short lag
      period, an intensive degradation occurred, which diminished in time and
      completely stopped in the end, despite large residual contaminations (residues of
      56% diesel fuel, 20% n-hexadecane and 3.5% phenanthrene at the initial loadings
      of each 3000 mg/kg). The remaining pollutant content was influenced by the kind
      of hydrocarbon but was nearly independent of its initial loading. According to a
      model-aided analysis of the carbon dioxide production during remediation, the
      observed stagnation of degradation was caused by a limited bioavailability of the
      pollutants. The degradation in the soil-free aqueous phase was more extensive
      than in the soil, which suggests that the limited bioavailability in the soil can
      be attributed mainly to matrix-dependent rather than substrate-dependent
      influences. Generally, fine particles and organic matter are mainly responsible
      for the adsorption of pollutants to the soil matrix. Our sandy soil also bound
      hydrocarbons adsorptively although it contained neither silty material nor
      significant amounts of organic matter. As shown by Brunauer Emmett Teller (BET)
      analysis, the soil particles were covered by micropores, which enlarged the soil
      surface by a factor of 120 in comparison with the macroscopic surface area. The
      microporosity is the reason for the hydrocarbons being more strongly adsorbed to
      the sandy soil than expected.

PMID- 10077827
TI  - Disposable sensor for measuring the biochemical oxygen demand for nitrification
      and inhibition of nitrification in wastewater.
AB  - A disposable-type microbial sensor was developed for the determination of both
      the biochemical oxygen demand for nitrification (N-BOD) and inhibiting effects on
      nitrifying bacteria. The sensor was based on the respiratory activity of
      nitrifying bacteria immobilized on a miniature oxygen electrode. Typical response
      times for measuring N-BOD of ammonium standard solutions as well as of wastewater
      samples were in the range of 6-12 min. A dynamic evaluation of the signals after
      a measuring time of 120 s also resulted in good reproducibility and sensitivity.
      A daily profile of a municipal sewage plant was recorded, comparing the biosensor
      data with two standard methods. For the measurement of nitrification-inhibiting
      effects a 120-s dynamic signal evaluation was preferred to a steady-state method
      because of the long recovery times resulting from extended exposure to
      inhibitors. However, steady-state measurement techniques allowed allylthiourea
      detection with a ten times higher sensitivity. Because of the advantages of this
      miniaturized electrode, e.g. short response time, simple measuring procedure and
      low costs of production, this sensor system is considered to be suitable for
      commercial application in environmental analysis.

PMID- 10077828
TI  - Acaloleptins A: inducible antibacterial peptides from larvae of the beetle,
      Acalolepta luxuriosa.
AB  - We purified and characterized three structurally related antibacterial peptides
      with a molecular mass of 8 kDa (acaloleptins A1, A2, and A3) from the hemolymph
      of immunized larvae of the Udo longicorn beetle, Acalolepta luxuriosa. These
      peptides have the same 6 N-terminal amino acid residues and show potent
      antibacterial activity against some Gram-negative bacteria. The three peptides
      are thought to be isoforms. Reverse phase HPLC analysis of the hemolymph of
      immunized and naive larvae showed that acaloleptins A1, A2, and A3 were inducible
      and suggested that all three peptides were produced in a single insect. We
      determined the complete amino acid sequence of acaloleptin A1: Acaloleptin A1
      consists of 71 amino acid residues and shares significant sequence similarity
      with coleoptericin and holotricin 2, which were isolated from other coleopteran
      insects. Furthermore, the 29 C-terminal residues of acaloleptin A1 had 40%
      identity with the 30 C-terminal residues of hymenoptaecin found in honeybees.
      Arch. Insect Biochem.

PMID- 10077829
TI  - Occurrence of ion transport peptide (ITP) and ion transport-like peptide (ITP-L)
      in orthopteroids.
AB  - Comparison of the sequence and biological activity of ITP-related proteins from
      other insects on Schistocerca hindgut will provide further understanding of ITP
      interaction with its receptor (ITPR) and may thus open new avenues of insect pest
      control if good ITPR antagonists can be developed. Using a specific bioassay
      (measurement of ileal Cl- transport) and Western blot analysis with antibodies
      raised to Schistocerca ion transport peptide (ScgITP) sequences, we demonstrate
      stimulatory ITP-related peptides in the corpora cardiaca (CC) of several
      othopteran insects (Schistocerca gregaria, Locusta migratoria, Melanoplus
      sanguinipes, Xanthippus corallipes, Carausius morosus, Periplaneta americana and
      Acheta domesticus.). For the first time, we have immunologically detected ITP in
      Schistocerca brain, the tissue in which ITP transcripts are found and which has
      some activity in the bioassay. Neither reciprocal bioassays nor immunological
      results reveal any differences between two locust species, Locusta and
      Schistocerca, which is consistent with cDNA analysis. Using Schistocerca-derived
      primers and the polymerase chain reaction (PCR), we show that Locusta brain
      contains RNA encoding for peptides with identical sequence to ScgITP and with
      only a single neutral amino acid change from Schistocerca ion transport-like
      peptide (ScgITP-L). We present evidence that ITP-L transcripts are present in at
      least 3 locust/grasshopper genera but have been unable to detect ITP-L peptide to
      date in any tissues assayed by Western blotting at a detection limit of 0.8
      pmol/tissue. Results indicate high conservation of ITP structure and biological
      activity among these orthopteroids, in contrast to several other insect orders.

PMID- 10077830
TI  - Bacterial alpha-glucan phosphorylases.
AB  - Although glycogen and other alpha-1,4-D-glucan storage polysaccharides are
      present in many bacteria, only few glucan phosphorylases from bacteria have been
      identified and characterised on the protein or gene level. All bacterial
      phosphorylases follow the same catalytic mechanisms as their plant and vertebrate
      counterparts, but differ considerably in terms of their substrate specificity and
      regulation. The catalytic domains are highly conserved while the regulatory sites
      are only poorly conserved. The degree of conservation between bacterial and
      mammalian phosphorylases is comparable to that of other non-mammalian and
      mammalian alpha-glucan phosphorylases. Only for maltodextrin phosphorylase from
      E. coli the physiological role of the enzyme in the utilisation of maltodextrins
      is known in detail; that of all other phosphorylases remains still unclear. Roles
      in regulation of endogenous glycogen metabolism in periods of starvation, and
      sporulation, stress response or quick adaptation to changing environments are
      imaginable.

PMID- 10077831
TI  - Acquisition of aluminum tolerance in Saccharomyces cerevisiae by expression of
      the BCB or NtGDI1 gene derived from plants.
AB  - Eleven aluminum stress-induced genes derived from plants (wheat, Arabidopsis and
      tobacco) were introduced into Saccharomyces cerevisiae to test if expression of
      these genes confers Al tolerance. Al sensitivity tests showed that expression of
      two genes, either an Arabidopsis gene for blue copper binding protein (BCB), or a
      tobacco gene for the GDP dissociation inhibitor (NtGDI1), conferred Al tolerance.
      Determinations of total content and localization of Al ions in these
      transformants suggested that the BCB gene product functions in restricting Al
      uptake, while expression of the NtGDI1 gene promotes release of Al ions after
      uptake.

PMID- 10077832
TI  - Identification of three additional femAB-like open reading frames in
      Staphylococcus aureus.
AB  - Three new proteins, FmhA, FmhB and FmhC, with significant identities to FemA and
      FemB were identified in the Staphylococcus aureus (ATCC 55748) genome database.
      They were mapped to the SmaI-C, SmaI-H and SmaI-A fragments of the S. aureus 8325
      chromosome, respectively. Whereas insertional inactivation of fmhA and fmhC had
      no effects on growth, antibiotic susceptibility, lysostaphin resistance, or
      peptidoglycan composition of the strains, fmhB could not be inactivated, strongly
      suggesting that fmhB may be an essential gene. As deduced from the functions of
      FemA and FemB which are involved in the synthesis of the peptidoglycan
      pentaglycine interpeptide, FmhB may be a candidate for the postulated FemX
      thought to add the first glycine to the nascent interpeptide.

PMID- 10077833
TI  - Identification and linkage mapping of the phsA gene of Aspergillus nidulans,
      where mutation affects growth and pigmentation of colonies in a temperature- and
      pH-dependent way.
AB  - We report the isolation and characterization of a mutant strain of the mold
      Aspergillus nidulans showing an altered response to environmental pH, including a
      reduction in its pH range for growth and the production of a melanin-like pigment
      at alkaline pH. We also show that the mutant strain is not detergent-sensitive
      and that its acid sensitivity is osmotically remediable with 0.5 M NaCl or 1.0 M
      sorbitol. Furthermore, the mutant phenotype is temperature-remediable with
      respect to pigmentation, extent of conidiation and growth diameter, with the
      restoration of a wild-type phenotype to the mutant strain being observed at 28
      degrees C. On the other hand, the severity of the mutant phenotype is increased
      at 40 degrees C. Genetic analysis shows that this pH- and temperature-sensitive
      mutation, named phsA1, is located on the right arm of linkage group I of A.
      nidulans, between pabaA and yA, and that mutation phsA1 is recessive.

PMID- 10077834
TI  - Induction of humoral and cellular immune responses in mice by a recombinant
      fowlpox virus expressing the E2 protein of bovine viral diarrhea virus.
AB  - A recombinant fowlpox virus (rFPV/E2) expressing the E2 protein of bovine viral
      diarrhea virus (BVDV) was constructed and characterized. Mice were immunized with
      recombinant virus and both humoral and cellular immune responses were studied.
      rFPV/E2 induced BVDV-specific antibodies which were detected by ELISA. In
      addition, mouse sera were shown to neutralize BVDV. A cytokine ELISA assay
      revealed that mice vaccinated with rFPV/E2 induced 7-fold more interferon-gamma
      than parental fowlpox virus.

PMID- 10077835
TI  - Repression of nitrogenase by ethanol in nitrogen-deprived cultures of Rhodovulum
      sulfidophilum.
AB  - Light-dependent H2 evolution did not occur in nitrogen-deprived cultures of
      Rhodovulum sulfidophilum in the presence of ethanol. When ethanol was added to
      cells which had been grown with ammonia, derepression of the nitrogen fixation
      genes (nifHD) was inhibited at an ethanol concentration of 1 mM. On the other
      hand, when cells had nitrogenase-catalyzed proton-reducing activity prior to
      ethanol addition, reduction of the nifHD transcript level did not occur after the
      addition. In cells grown with ammonia, concomitant addition of an auxiliary
      oxidant such as dimethylsulfoxide or sodium bicarbonate resulted in derepression
      of nitrogenase activity in the presence of ethanol. These results suggest that
      the electron-accepting process is necessary for derepression of nif genes in
      cultures which use ethanol as the electron donor.

PMID- 10077836
TI  - Molecular characterization of a carbapenem-hydrolyzing beta-lactamase from
      Chryseobacterium (Flavobacterium) indologenes.
AB  - Chryseobacterium (Flavobacterium) indologenes 001 clinical strain was resistant
      to several beta-lactam classes including carbapenems. Shotgun cloning experiments
      of Sau3AI restricted genomic DNA of C. indologenes 001 into pBKCMV cloning vector
      followed by transformation into Escherichia coli DH10B gave one recombinant
      plasmid possessing a 4.2-kb DNA insert. It encoded a pI 7.2 beta-lactamase of 239
      amino acids (IND-1) which is a metallo-enzyme with a broad spectrum beta-lactam
      hydrolysis profile. This class B carbapenem-hydrolyzing beta-lactamase shares the
      highest identity (43%) with BlaB from C. meningosepticum, thus showing
      heterogeneity of carbapenem-hydrolyzing beta-lactamases in Chryseobacterium spp.

PMID- 10077837
TI  - NADH reoxidation does not control glycolytic flux during exposure of respiring
      Saccharomyces cerevisiae cultures to glucose excess.
AB  - Introduction of the Lactobacillus casei lactate dehydrogenase (LDH) gene into
      Saccharomyces cerevisiae under the control of the TPI1 promoter yielded high LDH
      levels in batch and chemostat cultures. LDH expression did not affect the
      dilution rate above which respiro-fermentative metabolism occurred (Dc) in
      aerobic, glucose-limited chemostats. Above Dc, the LDH-expressing strain produced
      both ethanol and lactate, but its overall fermentation rate was the same as in
      wild-type cultures. Exposure of respiring, LDH-expressing cultures to glucose
      excess triggered simultaneous ethanol and lactate production. However, the
      specific glucose consumption rate was not affected, indicating that NADH
      reoxidation does not control glycolytic flux under these conditions.

PMID- 10077838
TI  - Increased heavy metal sensitivity of Escherichia coli producing the expression
      product of priA gene derived from the basidiomycete Lentinus edodes.
AB  - We have previously isolated a developmentally regulated novel gene, priA, from
      the basidiomycete Lentinus edodes. The deduced PRIA protein contains the two set
      of motifs similar to a 'zinc finger' typified by transcription factor TFIIIA and
      the motif of a 'zinc cluster' observed in metallothioneins. It also contains a
      hydrophobic N-terminal sequence. Here Escherichia coli cells producing PRIA were
      found to show a remarkable sensitivity to zinc ion and other heavy metal ions
      such as nickel and cadmium. Deletion analysis of PRIA revealed that the zinc
      binding motifs and the hydrophobic N-terminal sequence are responsible for
      conferring the heavy metal sensitivity on the host cells.

PMID- 10077839
TI  - Phylogenetic relationships of symbiotic methanogens in diverse termites.
AB  - Termites harbor symbiotic microorganisms in their gut which emit methane. The
      phylogeny of the termite methanogens was inferred without cultivation based on
      nucleotide sequences of PCR-amplified 16S ribosomal RNA genes. Seven methanogen
      sequences from four termite species were newly isolated, and together with those
      previously published, these sequences were phylogenetically compared. The termite
      methanogen sequences were divided into three clusters. Two clusters of sequences,
      derived from the gut DNA of so-called higher termites, were related to
      methanogens in the orders Methanosarcinales or Methanomicrobiales. All of the
      sequences in the case of lower termites were closely related to the genus
      Methanobrevibacter. However, most of the termite symbionts were found to be
      distinct from known methanogens. They are not dispersed among diverse methanogen
      species, but rather formed unique lineages in the phylogenetic trees.

PMID- 10077840
TI  - Properties of uracil transport by vegetative mycelium of Trichoderma viride.
AB  - The transport of radioactively labelled uracil into submerged mycelium of T.
      viride was measured by means of a membrane filtration technique. It was found to
      be time-dependent (up to 90 min) and concentration-dependent (up to 8 mmol l-1).
      Its concentration dependence was biphasic and consisted from the saturatable part
      (at the uracil concentration below 0.2 mmol l-1) with KM = 0.08 +/- 0.02 mmol l-1
      and Vmax = 1.74 +/- 0.3 nmol (mg dry wt.)-1 h-1, and from the region at higher
      uracil concentration which showed only a weak saturatability with the substrate.
      The transport measured in the saturatable part of the curve was also pH- and
      temperature-dependent. The optimal pH was between 5.4 and 6.4 and the optimal
      temperature was at 37 degrees C. The activation energy of 54 kJ mol-1 and the
      temperature quotient of Q10 = 2.1 could be calculated from the temperature
      dependence. The entry of uracil was in part inhibited by nucleobases and their
      analogues, nucleosides, nucleotides and amino acids. The inhibitors had similar
      inhibitory efficiency about 50% at 0.2 mmol l-1. 3,3',4',5
      tetrachlorosalicylanilide (TCS), the uncoupling agent, significantly inhibited
      the uracil transport, but its inhibitory efficiency decreased upon increasing the
      uracil concentration. Ionophore antibiotics valinomycin and monensin also
      inhibited the uracil transport. Inhibitors of RNA-polymerase, rifamycin and
      rifampicin were without effect. The results suggest that at low uracil
      concentrations (below 0.2 mmol l-1), its transport is mediated by a carrier and
      is driven by the electrochemical potential of protons. At higher uracil
      concentrations, the transport may be driven by the concentration difference of
      uracil with the contribution of the protonmotive force. It is feasible that
      inhibitors of uracil transport tested exert their inhibition by the dissipation
      of the driving force rather than by the direct competition with the substrate
      binding site.

PMID- 10077841
TI  - Involvement of Nha1 antiporter in regulation of intracellular pH in Saccharomyces
      cerevisiae.
AB  - The Nha1 antiporter is involved in regulation of intracellular pH in
      Saccharomyces cerevisiae. We report that deletion of the NHA1 gene resulted in an
      increase of cytoplasmic pH in cells suspended in water or acidic buffers.
      Addition of KCl or NaCl to exponentially growing cells lowered the internal pH
      but the difference between cells with or without NHA1 was maintained. Addition of
      KCl to starved cells resulted in much higher alkalinization of cytoplasmic pH in
      a strain lacking Nha1p compared to the wild-type or Nha1p-overexpressing strains.
      The H+/K+(Na+) exchange mechanism of Nha1p was confirmed in reconstituted plasma
      membrane vesicles.

PMID- 10077842
TI  - Destruction of Salmonella typhimurium, Escherichia coli O157:H7 and Listeria
      monocytogenes in chicken manure by drying and/or gassing with ammonia.
AB  - Escherichia coli O157:H7 and Listeria monocytogenes were able to grow for a
      period of 2 days in fresh chicken manure at 20 degrees C with a resulting 1-2 log
      units increase in CFU; Salmonella typhimurium remained stable. Prolongation of
      the storage time to 6 days resulted in a 1-2 log decreases of S. typhimurium
      compared to the initial count and a 3-4 log decrease of E. coli O157:H7; the
      number of L. monocytogenes did not decrease below the initial. These changes were
      accompanied by an increase in pH and accumulation of ammonia in the manure. The
      destruction of the three microorganisms was greatly increased by drying the
      manure to a moisture content of 10% followed by exposure to ammonia gas in an
      amount of 1% of the manure wet weight; S. typhimurium and E. coli O157:H7 were
      reduced by 8 log units, L. monocytogenes by 4.

PMID- 10077843
TI  - Identification and characterization of 6-dehydroVB-A reductase from Streptomyces
      antibioticus.
AB  - Streptomyces antibioticus NF-18 is a hyperproducing strain of a Streptomyces
      hormone, virginiae butanolide A (VB-A), that induces virginiamycin production of
      S. virginiae at nanomolar concentrations. To characterize the biosynthetic
      pathway of VB-A, we identified and characterized for the first time the 6-dehydro
      VB-A reductase that is responsible for the final reduction step in the
      biosynthesis. Assay protocols and stabilization conditions were established. The
      6-dehydro VB-A reductase was found to require NADPH, not NADH, as a coenzyme. The
      K(m) values of the enzyme for NADPH and (+/-)-6-dehydro VB-A were determined to
      be 50 +/- 2 microM and 100 +/- 5 microM, respectively. Ultracentrifugation
      experiments revealed that 6-dehydro VB-A reductase was present almost exclusively
      in the 100,000 x g supernatant fraction, indicating that the enzyme is a
      cytoplasmic-soluble protein. The M(r) of the native 6-dehydro VB-A reductase was
      estimated to be 82,000 +/- 3000 by molecular sieve HPLC. The optimal pH was found
      to be 6.7 +/- 0.2.

PMID- 10077844
TI  - Involvement of host cell tyrosine phosphorylation in the invasion of HEp-2 cells
      by Bartonella bacilliformis.
AB  - We have provided evidence that exposure of human cells to protein kinase
      inhibitors results in decreased invasion of these cells by Bartonella
      bacilliformis in a dose-dependent manner. Preincubation of human laryngeal
      epithelial cells in the presence of genistein, a tyrosine protein kinase
      inhibitor, decreased the invasion of these cells by B. bacilliformis
      significantly. Further, exposure of normal human umbilical vein endothelial cells
      to staurosporine, a potent inhibitor of protein kinase C and some tyrosine
      protein kinases, resulted in a considerable reduction in the number of organisms
      internalized by these cells. Moreover, Bartonella infection of HEp-2 cells
      induced tyrosine phosphorylation of several Triton X-100 soluble proteins with
      approximate molecular masses of 243, 215 179, 172 (doublet), 160, 145 and 110 kDa
      that were absent or reduced in the presence of genistein in cells after 1 h of
      infection. Exposure of HEp-2 cell monolayers to anti-alpha 5 and anti-beta 1
      chain integrin monoclonal antibodies resulted in a moderate decrease in the
      invasion of these cells, suggesting a possible role of alpha 5 beta 1 integrins
      in the uptake of Bartonella into nucleated cells.

PMID- 10077845
TI  - Aerosol route enhances the contamination of intact eggs and muscle of
      experimentally infected laying hens by Salmonella typhimurium DT104.
AB  - Commercial laying hens were infected with Salmonella typhimurium DT104 strain 16
      alternatively via the crop (10(7) cfu per bird) or by an aerosol delivered
      directly to the beaks using a Collison nebuliser and Henderson apparatus (2 x
      10(2) or 2 x 10(4) cfu per bird). Infection by both routes caused systemic
      infection and prolonged contamination of faeces. Contamination rates of eggs and
      muscle were much higher following the aerosol challenges despite the much lower
      doses given by this route. The frequency of Salmonella isolation from eggs rose
      from 1.7% following oral challenge to 14% and 25%, for each of the aerosol
      challenges respectively, and the frequency of isolation from muscle rose from 0%
      following the oral challenge to 27% following each of the aerosol challenges.

PMID- 10077846
TI  - Evaluation of the API test, phosphatidylinositol-specific phospholipase C
      activity and PCR method in identification of Listeria monocytogenes in meat
      foods.
AB  - The aim of this work was to compare the possibility of identifying Listeria
      monocytogenes strains isolated from meat and sausage on the basis of the API
      Listeria test, production of phosphatidylinositol-specific phospholipase C (PI
      PLC) and polymerase chain reaction (PCR) for a DNA fragment of the hlyA gene
      encoding listeriolysin O. Forty-six strains were isolated and examined. The
      lethality of some Listeria isolates for BALB/c mice was also determined. In this
      study, all isolates identified as L. monocytogenes in the API test gave a
      positive signal in the PCR. Listeriae identified as L. innocua or L. welshimeri
      in the API test were negative in the PCR conducted with the primers for
      listeriolysin O. All strains identified as L. monocytogenes on the basis of the
      API test and the PCR produced PI-PLC. However, this activity was not limited to
      the bacteria of this species. Four out of 17 L. innocua and three out of 10 L.
      welshimeri isolates were PI-PLC-positive. None of the L. innocua or L. welshimeri
      isolates (neither PI-PLC+ or PI-PLC-) showed lethality for BALB/c mice. In
      contrast, two L. monocytogenes isolates as well as a reference L. monocytogenes
      strain killed all mice used for the experiment.

PMID- 10077847
TI  - Low target site specificity of an IS6100-based mini-transposon, Tn1792, developed
      for transposon mutagenesis of antibiotic-producing Streptomyces.
AB  - To improve transposon mutagenesis of antibiotic-producing Streptomyces, a mini
      transposon, Tn1792, was constructed, based on IS6100, originally isolated from
      Mycobacterium fortuitum. Easily manageable transposition assays were developed to
      demonstrate inducible transposition of Tn1792 into the Streptomyces genome from a
      temperature-sensitive delivery plasmid. Introduction of the selectable aac1 gene
      between the inverted repeats in Tn1792 allowed for both reliable identification
      of transposition events in Streptomyces, and also subsequent cloning of
      transposon-tagged sequences in Escherichia coli. This enabled the target site
      specificity of Tn1792 to be determined at nucleotide resolution, revealing no
      significant shared homology between different target sites. Consequently, Tn1792
      is well suited for random mutagenesis of Streptomyces.

PMID- 10077848
TI  - Molecular analysis of the region encoding the lytic system from Oenococcus oeni
      temperate bacteriophage phi 10MC.
AB  - Malolactic fermentation by Oenococcus oeni is a crucial step in wine-making. Oe.
      oeni phages are thought to be responsible for fermentation failures, yet they
      have received little attention. After a molecular analysis concerning the phage
      phi 10MC integration system, this paper focuses on the lytic system. The attP
      (phage attachment site)-flanking region has been cloned and sequenced. The 1296
      bp lysin gene (Lys) was identified in this region. The deduced amino acid
      sequence showed classical structural features of phage lysins, and this gene
      product expressed in Escherichia coli had a lytic activity against Oe. oeni.
      Downstream of Lys, a second ORF was present (P163). According to its amino acid
      sequence and the location of its gene, the product could be the phi 10MC holin.
      This study shows that the genomic organization of phage phi 10MC attP-flanking
      regions is very similar to that of other lactic acid bacteriophages.

PMID- 10077849
TI  - Purification and characterization of a 40.8-kDa cutinase in ungerminated conidia
      of Botrytis cinerea Pers.: Fr.
AB  - Cytoplasmic soluble proteins from ungerminated conidia of Botrytis cinerea
      exhibited cutinase activity. A 40.8-kDa cutinase was purified to homogeneity from
      this crude conidial protein extract. This cutinase does not correspond either to
      constitutive or to induced lytic cutin enzymes already described by other
      authors. The possible role of this constitutive cutinase in the induction of
      other cutinolytic proteins in the early stages of infection of plants by B.
      cinerea is discussed.

PMID- 10077850
TI  - Candida albicans hyphal invasion: thigmotropism or chemotropism?
AB  - Hyphae of the human pathogenic fungus Candida albicans exhibit thigmotropic
      behaviour in vitro, in common with phytopathogenic and saprotrophic fungi. An
      examination of the literature on C. albicans hyphal penetration of epithelial and
      endothelial membranes does not support the premise that hyphal thigmotropism
      plays a major role in tissue invasion. Further experimentation is now required to
      assess thigmotropic behaviour on host membranes and vaginal epithelial cells are
      suggested as a test model. It is proposed that while thigmotropism may and
      invasion of tissue invaginations, chemotropism can explain C. albicans hyphal
      invasion patterns of both endothelium and epithelium.

PMID- 10077851
TI  - FtsH--a single-chain charonin?
AB  - The ftsH gene encodes an ATP- and Zn(2+)-dependent metalloprotease with a
      molecular mass of about 70 kDa. It was first identified in Escherichia coli where
      it is also designated hflB, tolZ or mrsC, and seems to be present in most if not
      all bacteria. The FtsH protein is anchored to the cytoplasmic membrane via two
      transmembrane regions in such a way that the very short amino- and the long
      carboxy-termini are exposed into the cytoplasm. FtsH is member of the AAA family
      (ATPases associated with a variety of cellular activities) which are
      characterized by a module of about 200 amino acid residues in length containing
      an ATP-binding site. In Escherichia coli, FtsH forms a complex with a pair of
      periplasmically exposed membrane proteins, HflK and HflC. The E. coli enzyme is
      required for proteolytic degradation of some unstable proteins that include both
      soluble regulatory proteins such as sigma 32 (heat-shock sigma factor) and phage
      lambda CII (transcriptional activator), and membrane proteins including
      uncomplexed forms of SecY (forms the translocon together with SecE and SecG) and
      the a subunit of the F0 complex of the H(+)-ATPase. Its activity can be modulated
      by the HflKC proteins, by another membrane protein designated YccA which can
      transiently associate with both the FtsH and the HflKC proteins, or by small
      peptides such as CIII encoded by phage lambda (involved in lysogenization) or
      SpoVM (needed for sporulation) encoded by Bacillus subtilis. Besides being a
      protease, there is circumstantial evidence that FtsH also acts as a molecular
      chaperone. It influences protein assembly in and through the cytoplasmic membrane
      and associates with denatured alkaline phosphatase without degrading it.
      Therefore, FtsH may serve to maintain quality control of some cytoplasmic and
      membrane proteins. Such ATP-dependent proteases with intrinsic chaperone activity
      have been designated charonins.

PMID- 10077852
TI  - Enzymology of one-carbon metabolism in methanogenic pathways.
AB  - Methanoarchaea, the largest and most phylogenetically diverse group in the
      Archaea domain, have evolved energy-yielding pathways marked by one-carbon
      biochemistry featuring novel cofactors and enzymes. All of the pathways have in
      common the two-electron reduction of methyl-coenzyme M to methane catalyzed by
      methyl-coenzyme M reductase but deviate in the source of the methyl group
      transferred to coenzyme M. Most of the methane produced in nature derives from
      acetate in a pathway where the activated substrate is cleaved by CO
      dehydrogenase/acetyl-CoA synthase and the methyl group is transferred to coenzyme
      M via methyltetrahydromethanopterin or methyltetrahydrosarcinapterin. Electrons
      for reductive demethylation of the methyl-coenzyme M originate from oxidation of
      the carbonyl group of acetate to carbon dioxide by the synthase. In the other
      major pathway, formate or H2 is oxidized to provide electrons for reduction of
      carbon dioxide to the methyl level and reduction of methyl-coenzyme to methane.
      Methane is also produced from the methyl groups of methanol and methylamines. In
      these pathways specialized methyltransferases transfer the methyl groups to
      coenzyme M. Electrons for reduction of the methyl-coenzyme M are supplied by
      oxidation of the methyl groups to carbon dioxide by a reversal of the carbon
      dioxide reduction pathway. Recent progress on the enzymology of one-carbon
      reactions in these pathways has raised the level of understanding with regard to
      the physiology and molecular biology of methanogenesis. These advances have also
      provided a foundation for future studies on the structure/function of these novel
      enzymes and exploitation of the recently completed sequences for the genomes from
      the methanoarchaea Methanobacterium thermoautotrophicum and Methanococcus
      jannaschii.

PMID- 10077853
TI  - Nuclear movement in filamentous fungi.
AB  - One of the most striking features of eukaryotic cells is the organization of
      specific functions into organelles such as nuclei, mitochondria, chloroplasts,
      the endoplasmic reticulum, vacuoles, peroxisomes or the Golgi apparatus. These
      membrane-surrounded compartments are not synthesized de novo but are bequeathed
      to daughter cells during cell division. The successful transmittance of
      organelles to daughter cells requires the growth, division and separation of
      these compartments and involves a complex machinery consisting of cytoskeletal
      components, mechanochemical motor proteins and regulatory factors. Organelles
      such as nuclei, which are present in most cells in a single copy, must be
      precisely positioned prior to cytokinesis. In many eukaryotic cells the cleavage
      plane for cell division is defined by the location of the nucleus prior to
      mitosis. Nuclear positioning is thus absolutely crucial in the unequal cell
      divisions that occur during development and embryogenesis. Yeast and filamentous
      fungi are excellent organisms for the molecular analysis of nuclear migration
      because of their amenability to a broad variety of powerful analytical methods
      unavailable in higher eukaryotes. Filamentous fungi are especially attractive
      models because the longitudinally elongated cells grow by apical tip extension
      and the organelles are often required to migrate long distances. This review
      describes nuclear migration in filamentous fungi, the approaches used for and the
      results of its molecular analysis and the projection of the results to other
      organisms.

PMID- 10077854
TI  - Strategies for isolation of in vivo expressed genes from bacteria.
AB  - The discovery and characterization of genes specifically induced in vivo upon
      infection and/or at a specific stage of the infection will be the next phase in
      studying bacterial virulence at the molecular level. Genes isolated are most
      likely to encode virulence-associated factors or products essential for survival,
      bacterial cell division and multiplication in situ. Identification of these genes
      is expected to provide new means to prevent infection, new targets for,
      antimicrobial therapy, as well as new insights into the infection process.
      Analysis of genes and their sequences initially discovered as in vivo induced may
      now be revealed by functional and comparative genomics. The new field of
      virulence genomics and their clustering as pathogenicity islands makes feasible
      their in-depth analysis. Application of new technologies such as in vivo
      expression technologies, signature-tagged mutagenesis, differential fluorescence
      induction, differential display using polymerase chain reaction coupled to
      bacterial genomics is expected to provide a strong basis for studying in vivo
      induced genes, and a better understanding of bacterial pathogenicity in vivo.
      This review presents technologies for characterization of genes expressed in
      vivo.

PMID- 10077855
TI  - The role of clinical forensic medicine in cases of sexual child abuse.
AB  - The work of specialists in forensic medicine in those cases of child abuse that
      result in the killing of a child is defined and well known. It is less well
      defined in cases of (suspected) sexual abuse. The cases presented show the
      difficulties that arise if medical doctors and prosecutors are uncertain about
      the procedures that have to be followed or do not appreciate the value of
      objective findings. It is concluded that knowledge about necessary examinations
      by physicians, police officers and prosecutors has to be promoted in order to
      improve handling and (legal) outcome of these cases.

PMID- 10077856
TI  - Analysis of psilocybin and psilocin in Psilocybe subcubensis Guzman by ion
      mobility spectrometry and gas chromatography-mass spectrometry.
AB  - A new method has been developed for the rapid analysis of psilocybin and/or
      psilocin in fungus material using ion mobility spectrometry. Quantitative
      analysis was performed by gas chromatography-mass spectrometry after a simple one
      step extraction involving homogenization of the dried fruit bodies of fungi in
      chloroform and derivatization with MSTFA. The proposed methods resulted in rapid
      procedures useful in analyzing psychotropic fungi for psilocybin and psilocin.

PMID- 10077857
TI  - Supercritical fluid chromatography in forensic science: a critical appraisal.
AB  - The application of supercritical fluid chromatography (SFC) in forensic science
      is reviewed. The applications centre on the analysis of explosives and of drugs
      of abuse. The systems employed are discussed in the context of comparison with
      gas chromatography and high-performance liquid chromatography methods which are
      traditionally used for such analyses. The advantages and disadvantages of SFC
      over these methods are discussed. Recommendations are made for the developments
      which are required in SFC technology if it is to find greater application in
      forensic science.

PMID- 10077858
TI  - Deaths among homeless people in Istanbul.
AB  - The number of the homeless people in Istanbul, one of the largest cities in the
      world, is at present unknown. There has been no previous study in Turkey on cases
      and causes of death occurring among these individuals. In this paper, documents
      and autopsy reports of the Mortuary Section of the Council of Forensic Medicine,
      Istanbul, covering the period January 1st, 1991-December 31st, 1995, were
      reviewed. We established that there were 126 cases of death among homeless
      individuals in Istanbul during this period, 120 of them being males (95%), four
      (3%) females, and two (2%) transsexuals. Ninety-four corpses were found outdoors,
      32 indoors. No personal documents, such as identity cards, were found in 110
      individuals (87%), whereas only 16 individuals could be identified. Most deaths
      occurred in the age group of 41-50 years. One hundred and three of the cases
      (82%) died in the cold season between October and April. The deaths of 98 cases
      were attributable to natural causes, whereas the remaining 28 cases died from
      unnatural causes. Respiratory tract diseases occupied the first rank among cases
      of death from natural causes (44%). Alcohol abuse and other infections were
      further striking factors contributing to the fatal outcome. This is the first
      retrospective study on this topic in Turkey. However, more detailed and
      anterospectively programmed studies on this subject, a growing social problem,
      should be carried out.

PMID- 10077859
TI  - Spectrophotometric evaluation of postmortem lividity.
AB  - Under low ambient temperatures normally bluish postmortem lividity adopts a
      bright red or pink colour due to resaturation of haemoglobin with O2. The most
      important differential diagnosis in the presence of pink hypostasis is carbon
      monoxide poisoning. To answer the question if objective measuring methods allow
      differentiation of hypostasis with regard to cold exposition or carbon monoxide
      poisoning, spectrophotometric measurements were performed and the colorimetric
      measures as well as the spectral reflectance curves of the postmortem lividity
      were determined. The colorimetric measures CIE-L*a*b* showed similar values for
      all bright red livores mortis; differentiation between CO intoxication and cold
      exposition was not possible. Reflectance curves of pink hypostasis after cold
      storage showed the typical pattern of O2-rich blood with reflectance minima at
      wavelengths 541 nm and 576 nm and a reflectance maximum at 560 nm. Pink
      hypostasis because of carbon monoxide poisoning showed a shift of the reflectance
      maximum toward 555 nm and a flattened curve in all cases with COHb concentrations
      exceeding 52%, whereas these changes were not regularly observed with lower COHb
      levels.

PMID- 10077860
TI  - Conditions of solid-phase extraction for the mixture of organophosphates and
      synthetic pyrethroids in human body fluids.

PMID- 10077861
TI  - Testosterone modulates stimulation-induced calling behavior in Japanese quails.
AB  - Japanese quails have a variety of calling patterns depending on sex and age.
      Sexually mature adult males emit a characteristic crow which has a frequency
      modulated acoustical trill element. Recently we reported that the intercollicular
      nucleus of the mesencephalon is the vocal neural system for producing the
      distress call in untreated chick and the crowing vocalization in testosterone
      treated chick in Japanese quails. We postulated that the intercollicular nucleus
      could mediate this testosterone action on vocal behavior. The present study
      showed histologically that the intercollicular nucleus neurons of adult males
      have many more dendrites than those of females. The adult males produced the call
      with trill element with electrical stimulation of the intercollicular nucleus
      alone. Females produced the simple call, which has no frequency modulation, with
      electrical stimulation; 4 days after the testosterone treatment together with
      electrical stimulation, they also produced the call with trill element, the
      characteristic call of males. We suggest that the vocal neural system in the
      intercollicular nucleus is modulated by testosterone during development and
      produces the crow in males, and the intercollicular nucleus neurons in adults
      mediate the action of testosterone on vocal behavior. The crow of adult males
      could therefore be due to effects of testosterone on the neural mechanism in the
      intercollicular nucleus.

PMID- 10077862
TI  - Persistent inward currents in cultured Retzius cells of the medicinal leech.
AB  - Current-clamp studies of cultured leech Retzius cells revealed inward
      rectification in the form of slow voltage sags in response to membrane
      hyperpolarization. Sag responses were eliminated in Na(+)-free saline and blocked
      by Cs+, but not Ba2+. Voltage clamp experiments revealed a Cs(+)-sensitive inward
      current activated by hyperpolarization negative to -70 mV. Cs+ decreased the
      frequency of spontaneous impulses in Retzius cells of intact ganglia. Plateau
      potentials were evoked in Retzius cells following block of Ca2+ influx with Ni2+
      and suppression of K+ currents with internal tetraethylammonium. Plateau
      potentials continued to be expressed with Li+ as the charge carrier, but were
      eliminated when Na+ was replaced with N-methyl-D-glucamine. A persistent Na+
      current with similar pharmacology that activated positive to -40 mV and reached
      its peak amplitude near -5 mV was identified in voltage-clamp experiments.
      Inactivation of the persistent Na+ current was slow and incomplete. The current
      was revealed by slow voltage ramps and persisted for the duration of 5-s voltage
      steps. Persistent Na+ current may underlie Na(+)-dependent bursting recorded in
      neurons of intact ganglia exposed to Ca2(+)-channel blockers.

PMID- 10077863
TI  - Transient and persistent tetrodotoxin-sensitive sodium currents in squid
      olfactory receptor neurons.
AB  - Squid olfactory receptor neurons are primary bipolar sensory neurons capable of
      transducing water-born odorant signals into electrical impulses that are
      transmitted to the brain. In this study, we have identified and characterized the
      macroscopic properties of voltage-gated Na+ channels in olfactory receptor
      neurons from the squid Lolliguncula brevis. Using whole-cell voltage-clamp
      techniques, we found that the voltage-gated Na+ channels were tetrodotoxin
      sensitive and had current densities ranging from 5 to 169 pA pF-1. Analyses of
      the voltage dependence and kinetics revealed interesting differences from voltage
      gated Na+ channels in olfactory receptor neurons from other species; the voltage
      of half-inactivation was shifted to the right and the voltage of half-activation
      was shifted to the left such that a "window-current" occurred, where 10-18% of
      the Na+ channels activated and did not inactivate at potentials near action
      potential threshold. Our findings suggest that in squid olfactory neurons, a
      subset of voltage-gated Na+ channels may play a role in generating a pacemaker
      type current for setting the tonic levels of electrical activity required for
      transmission of hyperpolarizing odor responses to the brain.

PMID- 10077864
TI  - Temporal pattern of locomotor activity in Drosophila melanogaster.
AB  - The temporal pattern of locomotor activity of single Drosophila melanogaster
      flies freely walking in small tubes is described. Locomotor activity monitored by
      a light gate has a characteristic time-course that depends upon age and the
      environmental conditions. Several methods are applied to assess the complexity of
      the temporal pattern. The pattern varies according to sex, genotype, age and
      environmental conditions (food; light). Activity occurs clustered in bouts. The
      intrinsic bout structure is quantified by four parameters: number of light gate
      passages (counts) per bout, duration of a bout, pause between two successive
      bouts and mean bout period. In addition, the distribution of the periods between
      light-gate crossings (inter-count intervals) as function of inter-count interval
      duration reveals a power law, suggesting that the overall distribution of
      episodes of activity and inactivity has a fractal structure. In the dark without
      food, the fractal dimension which represents a measure of the complexity of the
      pattern is sex, genotype and age specific. Fractality is abolished by additional
      sensory stimulation (food; light). We propose that time-course, bout structure
      and fractal dimension of the temporal pattern of locomotor activity describe
      different aspects of the fly's central pattern generator for locomotion and its
      motivational control.

PMID- 10077865
TI  - Effects of GABA-mediated inhibition on direction-dependent frequency tuning in
      the frog inferior colliculus.
AB  - Earlier studies from our laboratory have shown that the frequency selectivity of
      neurons in the frog inferior colliculus is direction dependent. The goal of this
      study was to test the hypotheses that gamma-aminobutyric acid or GABA (but not
      glycine)-mediated synaptic inhibition was responsible for the direction
      dependence in frequency tuning, and that GABA acted through creation of binaural
      inhibition. We performed single unit recordings and investigated the unit's free
      field frequency tuning, and/or the unit's response to the interaural level
      differences (under dichotic stimulation), before and during local applications of
      antagonists specific to gamma-aminobutyric acid A and glycine receptors. Our
      results showed that application of bicuculline produced a broadening of free
      field frequency tuning depending on sound direction, i.e., more pronounced at
      azimuths at which the unit exhibited narrower frequency tuning under the pre-drug
      condition, thereby typically abolishing direction dependence in tuning.
      Application of strychnine produced no change in frequency tuning. The results
      from dichotic stimulation further revealed that bicuculline typically elevated
      and/or flattened the unit's interaural-level-difference response function,
      indicating a reduction in the strength of binaural inhibition. Our study provides
      evidence that gamma-aminobutyric acid-mediated binaural inhibition is important
      for direction dependence in frequency tuning.

PMID- 10077866
TI  - Energetics and kinetics of the prebiotic synthesis of simple organic acids and
      amino acids with the FeS-H2S/FeS2 redox couple as reductant.
AB  - The thermodynamics of the FeS-H2S/FeS2 redox couple and a select number of
      reactions critical to the synthesis of simple carboxylic acids and amino acids
      have been evaluated as a function of temperature. This thermodynamic evaluation
      shows that the reducing power of the FeS-H2S/FeS2 redox couple decreases
      drastically with temperature. By contrast the equilibria describing the reduction
      of CO2 and the formation of simple carboxylic acids and amino acids require an
      increasingly higher reducing power with temperature. Given these two opposite
      trends, the thermodynamic driving force for CO2 reduction and amino acid
      formation with the FeS-H2S/FeS2 redox couple as reductant diminishes with
      increasing temperature. An evaluation of the mechanism of CO2 reduction by the
      FeS-H2S/FeS2 couple suggests that the electron transfer from pyrrhotite to CO2 is
      hindered by a high activation energy, even though the overall reaction is
      thermodynamically favorable. By comparison the electron transfer from pyrrhotite
      to either CS2, CO, or HCOOH are far more facile. This theoretical analysis
      explains the results of experimental work by Keefe et al. (1995), Heinen and
      Lauwers (1996) and Huber and Wachtershauser (1997). The implication is that a
      reaction sequence involving the reduction of CO2 with the FeS-H2S/FeS2 couple as
      reductant is unlikely to initiate a proposed prebiotic carbon fixation cycle
      (Wachtershauser, 1988b; 1990b, 1990a, 1992, 1993).

PMID- 10077867
TI  - Sources and sinks for ammonia and nitrite on the early Earth and the reaction of
      nitrite with ammonia.
AB  - An analysis of sources and sinks for ammonia and nitrite on the early Earth was
      conducted. Rates of formation and destruction, and steady state concentrations of
      both species were determined by steady state kinetics. The importance of the
      reaction of nitrite with ammonia on the feasibility of ammonia formation from
      nitrite was evaluated. The analysis considered conditions such as temperature,
      ferrous iron concentration, and pH. For sinks we considered the reduction of
      nitrite to ammonia, reaction between nitrite and ammonia, photochemical
      destruction of both species, and destruction at hydrothermal vents. Under most
      environmental conditions, the primary sink for nitrite is reduction to ammonia.
      The reaction between ammonia and nitrite is not an important sink for either
      nitrite or ammonia. Destruction at hydrothermal vents is important at acidic pH's
      and at low ferrous iron concentrations. Photochemical destruction, even in a
      worst case scenario, is unimportant under many conditions except possibly under
      acidic, low iron concentration, or low temperature conditions. The primary sink
      for ammonia is photochemical destruction in the atmosphere. Under acidic
      conditions, more of the ammonia is tied up as ammonium (reducing its vapor
      pressure and keeping it in solution) and hydrothermal destruction becomes more
      important.

PMID- 10077868
TI  - Martian stable isotopes: volatile evolution, climate change and exobiological
      implications.
AB  - Measurements of the ratios of stable isotopes in the martian atmosphere and crust
      provide fundamental information about the evolution of the martian volatile and
      climate system. Current best estimates of the isotope ratios indicate that there
      has been substantial loss of gases to space and exchange of gases between the
      atmosphere and the crust throughout geologic time; exchange may have occurred
      through circulation of water in hydrothermal systems. Processes of volatile
      evolution and exchange will fractionate the isotopes in a manner that complicates
      the possible interpretation of isotopic data in terms of any fractionation that
      may have been caused by martian biota, and must be understood first. Key
      measurements are suggested that will enhance our understanding of the non
      biological fractionation of the isotopes and of the evolution of the martian
      volatile system.

PMID- 10077869
TI  - Peroxide-modified titanium dioxide: a chemical analog of putative Martian soil
      oxidants.
AB  - Hydrogen peroxide chemisorbed on titanium dioxide (peroxide-modified titanium
      dioxide) is investigated as a chemical analog to the putative soil oxidants
      responsible for the chemical reactivity seen in the Viking biology experiments.
      When peroxide-modified titanium dioxide (anatase) was exposed to a solution
      similar to the Viking labeled release (LR) experiment organic medium, CO2 gas was
      released into the sample cell headspace. Storage of these samples at 10 degrees C
      for 48 hr prior to exposure to organics resulted in a positive response while
      storage for 7 days did not. In the Viking LR experiment, storage of the Martian
      surface samples for 2 sols (approximately 49 hr) resulted in a positive response
      while storage for 141 sols essentially eliminated the initial rapid release of
      CO2. Heating the peroxide-modified titanium dioxide to 50 degrees C prior to
      exposure to organics resulted in a negative response. This is similar to, but not
      identical to, the Viking samples where heating to approximately 46 degrees C
      diminished the response by 54-80% and heating to 51.5 apparently eliminated the
      response. When exposed to water vapor, the peroxide-modified titanium dioxide
      samples release O2 in a manner similar to the release seen in the Viking gas
      exchange experiment (GEx). Reactivity is retained upon heating at 50 degrees C
      for three hours, distinguishing this active agent from the one responsible for
      the release of CO2 from aqueous organics. The release of CO2 by the peroxide
      modified titanium dioxide is attributed to the decomposition of organics by outer
      sphere peroxide complexes associated with surface hydroxyl groups, while the
      release of O2 upon humidification is attributed to more stable inner-sphere
      peroxide complexes associated with Ti4+ cations. Heating the peroxide-modified
      titanium dioxide to 145 degrees C inhibited the release of O2, while in the
      Viking experiments heating to this temperature diminished but did not eliminated
      the response. Although the thermal stability of the titanium-peroxide complexes
      in this work is lower than the stability seen in the Viking experiments, it is
      expected that similar types of complexes will form in titanium containing
      minerals other than anatase and the stability of these complexes will vary with
      surface hydroxylation and mineralogy.

PMID- 10077870
TI  - Codons and hypercycles.
AB  - Several hypotheses on the origin of codon assignments imply that the present
      protein synthesizing machinery was already in place when the assignments were
      made. These are examined by computer modeling. The results do not suggest that
      assignments were optimized for resistance to reading and mutation errors, nor
      that the assignments are random. It is improbable that the number of species of
      amino acids increased in the course of evolution. An originally ambiguous
      dictionary is likely to have been subject to error catastrophe and is improbable.
      A relation between amino acid properties and their codons exists, and suggests
      that the codon assignments were established at the time of origin of the
      hypercycle, i.e. a system of aminoacyl synthetases which attaches amino acids to
      tRNA, and before the present protein synthesizing machinery was in place. The
      origin of a hypercycle is only possible if the system began with components which
      were catalytically active even when they did not form a self-replicating system.
      A model of such a system is proposed.

PMID- 10077871
TI  - The fate of heavy oil wastes in soil microcosms. I: A performance assessment of
      biotransformation indices.
AB  - A controlled soil microcosm study was used to evaluate the performance of
      selected oil biotransformation indices using samples of Nigerian crude, a blended
      ballast oil and No. 6 fuel oil. Biotic losses were demonstrated through loss of
      solvent extractable matter (SEM) and changes in class fraction distribution in
      weathered soil extracts relative to sterilised controls. GC-EI MS peak
      identification and quantification was achieved for selected (sigma) n-alkanes,
      the isoprenoid alkanes norpristane (iC18), pristane (iC19) and phytane (iC20),
      combined mono-substituted (1-, 2-, 3- and 9-) methylphenanthrenes (sigma
      methylphenanthrenes), combined dimethylphenanthrenes (sigma
      dimethylphenanthrenes) and the hopane isomers 17 alpha(H)21 beta(H)-hopane and 17
      alpha(H)21 beta(H)-30-norhopane. The [sigma n-alkanes:17 alpha(H)21 beta(H)
      hopane] index was most sensitive to oil biotransformation and most accurately
      reflected depletion of oil from contaminated soils in this study. This index was
      found to be the most reliable for the No. 6 fuel oil saturates, dropping from
      81.9 to 18.1 over the course of the 256-day microcosm study. In terms of
      sensitivity, and taking into account the results of an ANOVA analysis, the
      biotransformation indices most sensitive to oil biotransformation were (in order
      of decreasing sensitivity): [sigma C14-28:17 alpha(H)21 beta(H)-hopane] >> [sigma
      C14-28:sigma dimethylphenanthrenes] > [C18:phytane].

PMID- 10077872
TI  - The fate of heavy oil wastes in soil microcosms. II: A performance assessment of
      source correlation indices.
AB  - Chemical fingerprinting is commonly undertaken to assist in the resolution of
      multi-party liability disputes, particularly when contaminants have migrated
      beyond property boundaries, in litigation-driven environmental assessments
      related to oil spills, and in assessing potential environmental impacts following
      releases of petroleum products into the environment. In this paper, we present
      data relating to the performance of source correlation indices for selected heavy
      oils over the course of a 9-month microcosm study. The results obtained in this
      study demonstrated that hopane pair indices varied little in magnitude, and may
      therefore be considered reliable source correlation indices. Over the course of
      the 9-month microcosm study [17 alpha(H)21 beta(H)-norhopane: 17 alpha(H)21
      beta(H)-hopane] exhibited mean values of 0.7 +/- 0.1 for a heavy ballast oil, and
      mean values that varied between 0.6 and 0.7 (+/- 0.05) for a crude oil. Similarly
      [(17 alpha(H)21 beta(H)-homohopane (22S): 17 alpha(H)21 beta(H)-homohopane (22R)]
      gave a mean value of 1.3 (precisions less than 0.05) and [17 alpha(H)21 beta(H)
      bishomohopane: 17 alpha(H)21 beta(H)-methylhopane] varied between 1.3 and 1.6
      (precision up to 0.1) for the same crude oil. These source correlation indices
      may be used to support a correlation between fresh and weathered oil samples for
      source identification purposes involving heavy and crude oil contamination of the
      terrestrial environment.

PMID- 10077873
TI  - Trace elements total content and particle sizes distribution in the air
      particulate matter of a rural-residential area in north Italy investigated by
      instrumental neutron activation analysis.
AB  - The concentrations (ng/m3) of more than 30 trace elements have been determined in
      the total air particulate of a rural-residential area in north Italy. By
      collecting the aerosols with multistage impactors the distribution of the trace
      elements in the different size-fractionated particles has been also investigated.
      The fine 'inhalable' fraction with particles of less than 10 microns in
      equivalent aerodynamic diameter (PM10) as well as the subsequent finest
      'respirable' fractions with particles of 0-1.1 microns (alveolar), 1.1-4.6
      microns (bronchial) and 4.6-9 microns (tracheo-pharynx) have been analyzed and
      evaluated. Apart from Pb, Cd and, in some cases, Ni and Cu which have been
      determined by ETAAS (electrothermal atomic absorption spectroscopy), all
      measurements have been carried out by instrumental neutron activation analysis
      (INAA).

PMID- 10077874
TI  - Blood cadmium concentrations in the general population of Umbria, central Italy.
AB  - The aims of this study were (a) to assess blood cadmium (B-Cd) concentrations and
      to establish a tentative reference interval; (b) to identify significant
      determinants of B-Cd, in a population from Umbria, Central Italy, which was not
      occupationally exposed to cadmium (Cd). Four hundred and thirty-four healthy
      blood-donors volunteered to answer a questionnaire and provide a blood sample for
      B-Cd analysis, which was performed by graphite furnace atomic absorption
      spectrophotometry. Blood Cd concentrations ranged from non-detectable values,
      i.e. below 0.1 microgram/l up to 3.4 micrograms/l and were not normally
      distributed. The median values and the 95th percentiles were 0.7 and 2.0
      micrograms/l, respectively. Concentrations of B-Cd were more than double in
      smokers than in non-smokers, median values being 1.1 micrograms/l and 0.5
      microgram/l, respectively. In current smokers, B-Cd values correlated with the
      number of cigarettes smoked daily (rs = 0.40, P = 0.0001) and with the cumulative
      exposure to cigarette smoke (rs = 0.35, P = 0.0001). Concentrations of B-Cd
      correlated with age in the non-smokers, but not in the smokers and were
      significantly higher in women than in men only in the non-smokers. Both in
      smokers and non-smokers, B-Cd concentrations were similar in subjects living in
      urban or in rural areas. In the whole study population the lower and the upper
      tentative reference limit were < 0.1 and 2.2 micrograms/l, respectively, as
      computed by a non-parametric rank-based method. The upper limit was approximately
      double in smokers than in non-smokers (3.1 micrograms/l and 1.6 micrograms/l,
      respectively). Our results show that B-Cd concentrations in a general population
      from Umbria are in the range reported for general populations in Northern Italy
      and other European Countries. Smoking was the strongest determinant of B-Cd
      concentrations and age had a lesser effect.

PMID- 10077875
TI  - Non-occupational lead and cadmium exposure of adult women in Bangkok, Thailand.
AB  - This survey was conducted to examine the extent of the exposure of Bangkok
      citizens to lead (Pb) and cadmium (Cd), and to evaluate the role of rice as the
      source of these heavy metals. In practice, 52 non-smoking adult women in an
      institution in the vicinity of Bangkok, volunteered to offer blood, spot urine,
      boiled rice and 24-h total food duplicate samples. Samples were wet-ashed, and
      then analyzed for Pb and Cd by ICP-MS. Geometric means for the levels in blood
      (Pb-B and Cd-B) and urine (Pb-U and Cd-U as corrected for creatinine
      concentration), and also for dietary intake (Pb-F and Cd-F) were 32.3
      micrograms/l for Pb-B, 0.41 microgram/l for Cd-B, 2.06 micrograms/g creatinine
      for Pb-U, 1.40 micrograms/g creatinine for Cd-U, 15.1 micrograms/day for Pb-F and
      7.1 micrograms/day for Cd-F. Rice contributed 30% and 4% of dietary Cd and Pb
      burden, respectively. When compared with the counterpart values obtained in four
      neighboring cities in southeast Asia (i.e. Nanning, Tainan, Manila, and Kuala
      Lumpur), dietary Pb burden of the women in Bangkok was middle in the order among
      the values for the five cities. Pb level in the blood was the lowest of the
      levels among the five cities and Pb in urine was also among the low group. This
      apparent discrepancy in the order between Pb-B (i.e. the fifth) and Pb-F (the
      third) might be attributable to recent reduction of Pb levels in the atmosphere
      in Bangkok. Regarding Cd exposure, Cd levels in blood and urine as well as
      dietary Cd burden of Bangkok women were either the lowest or the next lowest
      among those in the five cities.

PMID- 10077876
TI  - Distribution of radiocaesium in an Austrian forest stand.
AB  - Within an Austrian spruce stand, vertical distribution of radiocaesium in soil as
      well as 137Cs concentration in different forest ecosystem compartments including
      spruce and surface water were investigated 10 years after the Chernobyl accident.
      The total 137Cs inventory in the forest was estimated to be 46 kBq m-2 (ref.
      date: 86-05-01). From the collected data annual input rates via litterfall of
      0.48% per year and output rates through waterflows of only 0.02% per year were
      derived. The results identify the high importance of forest soils as a sink for
      radiocaesium. The estimated ecological residence half-times turned out to be
      highest in the organic soil horizons (1-3 years per cm), whereas in mineral
      horizons the values decrease significantly. As a consequence, soil inventory
      represents more than 95% of the total, whereas only approximately 3.3% of the
      137Cs inventory is stored in the living biomass of spruce trees and a further
      0.5% in the phytomass of understorey vegetation.

PMID- 10077877
TI  - Baseline levels of Hsp 70, a stress protein and biomarker, in halibut from the
      Cook Inlet region of Alaska.
AB  - The levels of Hsp 70, a heat shock protein, was quantitatively determined in
      Pacific halibut, Hippoglossus stenolepis, from the Cook Inlet region in south
      central Alaska. A dot blot analysis using a monoclonal antibody for Hsp 70 was
      combined with a standard protein analysis to determine Hsp 70 levels in 26
      samples from gills. The average Hsp 70 concentration was 4.6 micrograms/mg, with
      levels ranging from 2.2 to 14.5 micrograms/mg total protein. Mercury in gill
      tissue also was measured and, in the 26 samples, only three samples had
      concentrations of mercury (X = 0.10 mg/kg, range = 0.09-0.11) above the minimum
      detection level.

PMID- 10077878
TI  - Antioxidant activity of cinnamon (Cinnamomum Zeylanicum, Breyne) extracts.
AB  - JUSTIFICATION: Lipid oxidation is one of the major changes that can occur during
      processing, distribution, storage and final preparation of foods. The oxidation
      could be prevented by adding synthetic or natural antioxidants in spite of safety
      of synthetic ones has been questioned. This situation promotes increasing demand
      for food additives of natural origin. OBJECTIVE: The objective of this study was
      to evaluate the antioxidant activity of cinnamon extracts. METHODS: Cinnamon
      samples were obtained at local market, milled (32 mesh sieve) and submitted to
      sequential extraction using as solvents: ether, methanol and water. The
      antioxidant activity in the extracts was measured by the b-carotene/linoleic acid
      system, at 50 degrees C and absorbances reading at 470 nm every 15 min intervals
      for 120 min. Two controls were used in this determination: one with synthetic
      antioxidant (BHT, 100 ppm) and other without antioxidant. The water extract was
      fraccionated using silica Gel 60 and 60G and through chromatographic processes:
      thin layer, (T.L.C.) and column, using BAW as mobile phase and ethylacetate,
      petroleum ether, methanol and water as eluent, respectively. RESULTS: The etheric
      (0.69 mg), methanolic (0.88 mg) and aqueous (0.44 mg) cinnamon extracts,
      inhibited the oxidative process in 68%; 95.5% and 87.5% respectively. The BHT
      control inhibited 80% oxidation. The spray reagents (1) beta-carotene/linoleic
      acid and (2) Fe Cl3/K3 Fe (CN)4 1% sol, showed spots in T.L.C. with antioxidant
      activity (1) and blue color (2), indicating the presence of phenolic compounds
      with Rf values of 0.50. Five fractions were obtained by column partition with
      antioxidant activity and the presence of phenolic compounds. SIGNIFICANCE: These
      results suggest that the cinnamon extracts can be used as food antioxidant
      together with the improvement of food palatability. Further studies are in
      processing of analysing the sinergic association of extracts with synthetic
      antioxidant and to identify compounds with antioxidant activity in cinnamon
      extracts.

PMID- 10077879
TI  - Determination of phenytoin in sections of head hair: a preliminary study to
      evaluate the history of drug use.
AB  - Phenytoin (PH) levels were determined in the head hair of twenty five patients
      (fourteen males and eleven females, aged from five to seventy seven years old)
      who were receiving this drug chronically. The assay method involved sectional
      hair analysis by dissolution and liquid phase extraction procedures, using both
      high pressure liquid chromatography (HPLC) and immunoassay (Abbott TDx)
      techniques. Five sections were studied, the first being the one closet to the
      root. The phenytoin levels of the hair sections ranged: a) 1st: 0.68 to 39.56
      micrograms/g (mean 16.12 micrograms/g), b) 2nd: 0.85 to 34.15 micrograms/g (mean
      9.45 micrograms/g), c) 3rd: 1.33 to 27.90 micrograms/g (mean 3.72 micrograms/g),
      d) 4th: 1.10 to 10.96 micrograms/g (mean 3.04 micrograms/g) and e) 5th: 1.05 to
      7.00 micrograms/g (mean 2.84 micrograms/g) according to the HPLC analysis. The
      immunoassay technique gave similar results. The mean values of phenytoin in the
      hair sections according to the immunoassay technique were: 16.28; 9.47; 3.77;
      3.22; 2.97 micrograms/g, respectively from the 1st to the 5th section. A
      reduction of drug concentrations in hair from the first to the consecutive
      segments was observed. Higher amounts of phenytoin were deposited in black,
      untreated hair in comparison to blond brown or grey hair. Phenytoin
      concentrations in hair sections correlated with the oral daily dosage of the
      drug. Our data indicate to the use of hair testing as a marker of the dosage
      history and evaluation of the compliance of patients under long treatment with
      phenytoin.

PMID- 10077880
TI  - Synthesis of biologically active bis-[4-amino-5-mercapto-1,2,4- triazol-3yl]
      alkanes and their derivatives.
AB  - The preparation of bis-(4-amino-5-mercapto-1,2,4-triazol-3yl)alkanes is
      described. These bis-(amino-mercapto-triazolyl) alkanes are characterized by
      analytical and spectral data. They are also characterized by the preparation of
      the Schiff bases by condensing them with various benzaldehydes and nitro furfural
      diacetate in dimethyl formamide-ethanol medium in the presence of concentrated
      sulphuric acid. The structures of Schiff bases are assigned based on analytical
      and spectral data. The newly synthesized compounds are screened for their
      antibacterial properties against Gram-positive and Gram-negative bacteria. Most
      of them showed significant activity.

PMID- 10077881
TI  - Effect of Tribulus terrestris L. saponin mixture on some smooth muscle
      preparations: a preliminary study.
AB  - Tribulus terrestris L. is an annual plant which has been commonly used in folk
      medicine as diuretic and against colic pains, hypertension and
      hypercholesterolemia in Turkey. This study investigated the effects of
      liophilized saponin mixture of this plant on several smooth muscle preparations
      in vitro. The liophilized material was obtained from dried and powdered T.
      terrestris L. by specific extraction method for saponins. Median lethal dose
      (LD50) of saponin mixture on Swiss albino mice was calculated according to
      Litchfield-Wilcoxon method via i.p. route. LD50 and its 95% confidence limits
      were 813 and 739-894 mg.kg-1 respectively. Saponin mixture has caused a
      significant decrease on peristaltic movements of isolated sheep ureter and rabbit
      jejunum preparations in a dose-dependent manner (p < 0.05). However it has been
      observed no effect on isolated rabbit aorta and its contractile response to KCl
      or noradrenaline (p > 0.05). According to these results it has been suggested
      that T. terrestris L. or its saponin mixture may be useful on some smooth muscle
      spasms or colic pains.

PMID- 10077882
TI  - Hemocompatibility of intravenous catheters: the influence of central or
      peripheric access.
AB  - The contact between the blood and any kind of material can lead to
      hemocompatibility issues that deserves some consideration. Midst some aspects to
      consider, special attention must be given to the rheology and the blood flow.
      Therefore, the speed blood influence in relation to the catheter type (central or
      peripheric) was studied in this report. It involved 129 patients from two school
      hospitals of Sao Paulo. The access (central or peripheric), different aspects
      related to the patients, proceeding and the type, nature and catheter origin were
      considered. One concludes that the blood incompatibility is time proportional,
      and that only the external surface shows blood compatibility differences,
      granting the peripheric catheters.

PMID- 10077883
TI  - [Transmyocardial laser revascularization].

PMID- 10077884
TI  - [Studies on the biological effects of disulufiram--effect of an active metabolite
      of disulfiram on the activity of delta-aminolevulinic acid synthetase].
AB  - The effect of diethyldithiocarbamic acid methyl eater (Me-DDC), a metabolite of
      disulfiram, on hepatic delta-aminolevulinic acid (ALA) synthetase activity was
      investigated in male rats. The results obtained were as follows: 1) When rats
      were given intraperitoneally Me-DDC at the dose levels of 0.0625, 0.125, 0.25 and
      0.50 mmol/kg, the activity of ALA synthetase showed a maximum level at a dose of
      0.125 mmol/kg. 2) ALA synthetase activity increased rapidly and reached a maximum
      level in about 2 hr after the intraperitoneal administration of Me-DDC (0.125
      mmol/kg). 3) Pretreatment with phenobarbital (an inducer of drug metabolizing
      enzymes) tended to depress the increase of ALA synthetase caused by Me-DDC,
      whereas pretreatment with SKF 525-A (an inhibitor of drug metabolizing enzymes)
      stimulated slightly the Me-DDC-induced increased of the enzyme. 4) The apparent
      Km value of the enzyme for glycine did not change but the Vmax value increased in
      Me-DDC-treated rats. 5) Actinomycin D (a potent inhibitor of DNA-dependent
      synthesis of RNA), when administered to rats before Me-DDC, completely prevented
      the induction of ALA synthetase caused by the latter compound. 6) Pretreatment
      with phorone (a glutathion depletor) 4 hr prior to the administration of Me-DDC
      completely inhibited the Me-DDC-induced increase of ALA synthetase.

PMID- 10077885
TI  - Sudden unexpected death from pulmonary thromboembolism--examination of antemortem
      chest X-ray.
AB  - An autopsy case of a woman who died suddenly from undiagnosed and untreated
      pulmonary thromboembolism (PTE) on her way home from the hospital is described in
      this report. She had complained of chest pain and dyspnea on exertion when she
      visited the hospital and a chest X-ray taken at that time showed remarkable
      manifestation of right heart failure and PTE, compared with former X-rays taken
      during previous visits to the hospital. In this report we present the findings of
      four chest X-rays of this patient, which had been taken both before and after the
      development of PTE.

PMID- 10077886
TI  - Hypothermic circulatory arrest and hypothermic perfusion for extensive disease of
      the thoracic and thoracoabdominal aorta.
AB  - BACKGROUND: Hypothermic cardiopulmonary bypass with or without an interval of
      circulatory arrest has been evaluated for the treatment of complex aortic disease
      of the descending thoracic and thoracoabdominal aorta. Hypothermia has a
      protective effect on spinal cord function, and its use should reduce the
      incidence of paraplegia and paraparesis in traditionally high-risk patients.
      Experimentally, the protective effect of hypothermia has been related to
      amelioration of excitotoxic injury by reduction of neurotransmitter release and
      to inhibition of delayed apoptopic cell death. METHODS: During a 12-year period,
      114 patients with descending thoracic or thoracoabdominal aortic disease
      underwent replacement of the involved aortic segments using hypothermic
      cardiopulmonary bypass and intervals of circulatory arrest. The mean age of the
      patients was 60 years (range 22 to 79 years). Acute or chronic dissection was
      present in 40 patients (35%). Sixty-four patients (56%) had Crawford Types I, II,
      or III thoracoabdominal aneurysms. RESULTS: The hospital mortality was 8% (9
      patients). Paraplegia occured in 2 and paraparesis in 1 of the 108 patients whose
      lower limb function was assessed postoperatively (2.8%). None of 40 patients with
      aortic dissection and none of the last 81 patients in the series developed
      paralysis. One patient developed renal failure that required dialysis.
      CONCLUSIONS: Our experience with hypothermic cardiopulmonary bypass and
      circulatory arrest confirms that hypothermia provides substantial protection
      against spinal cord ischemic injury. It allows complex operations on the
      descending thoracic and thoracoabdominal aorta to be performed with acceptable
      mortality, a low incidence of renal failure, and an incidence of other
      complications that does not exceed that reported with other techniques.

PMID- 10077887
TI  - Atrial fibrillation after coronary artery bypass grafting. An increase in high
      frequency atrial activity in patients with right coronary artery
      revascularization.
AB  - The increase in atrial high-frequency activity has been reported as a marker of
      the risk of paroxysmal atrial fibrillation. The presence of proximal right
      coronary artery disease is a predictor of atrial fibrillation after bypass
      surgery, however, the potential mechanism remains controversial. In this study,
      high-frequency atrial activity to clarify the electrophysiologic background for
      the predisposition to have proximal right coronary artery disease leading to
      atrial fibrillation after coronary revascularization was investigated. Before and
      soon after coronary revascularization, frequency analyses were performed on the
      100 ms segment at the end of signal-averaged P waves in 22 patients with right
      coronary artery disease as opposed to the 23 patients without disease. Under the
      spectrum curve, area ratio (AR50) and magnitude ratios (MR) were calculated as
      follows; AR50 = (area 20-50 Hz/0-20 Hz) x 100, and MR = (magnitude at 20, 30, 40
      and 50 Hz, respectively/maximal magnitude) x 100. In patients with proximal right
      coronary artery disease, high-frequency atrial components increased significantly
      in the 20 to 50 Hz range after coronary revascularization, and the incidence of
      postoperative atrial fibrillation was higher than in those without disease. In
      patients without right coronary artery disease, the frequency distribution of P
      waves was unchanged. Postoperatively, the two groups showed the same atrial
      frequency distribution. This data suggests that the increase in high-frequency
      atrial activity after right coronary artery revascularization might be associated
      with the pathogenesis of postoperative atrial fibrillation.

PMID- 10077888
TI  - Guideline of surgical management based on diffusion of descending necrotizing
      mediastinitis.
AB  - BACKGROUND: Descending necrotizing mediastinitis resulting from oropharyngeal
      abscess, is a serious, life-threatening infection. Exisiting strategies for
      surgical management, such as transcervical mediastinal drainage or aggressive
      thoracotomic drainage, remain controversial. METHODS: Four patients, (three males
      and one female) were treated for descending necrotizing mediastinitis resulting
      from oropharyngeal infection. Two had peritonsillar abscesses, while the others
      experienced dental abscess and submaxillaritis. Descending necrotizing
      mediastinitis received its classification according to the degree of diffusion of
      infection diagnosed by computed tomography. Mediastinitis in two cases,
      (Localized descending necrotizing mediastinitis-Type I), was localized to the
      upper mediastinal space above the carina. In the others, infection extended to
      the lower anterior mediastinum (Diffuse descending necrotizing mediastinitis-Type
      IIA), and to both anterior and posterior lower mediastinum (Diffuse descending
      necrotizing mediastinitis-Type IIB). The spread of infection to the pleural
      cavity occurred in three cases. RESULTS: The surgical outcome concerning each of
      the patients was successful. Radical cervicotomy (unilateral in three patients,
      bilateral in the other) in conjunction with mechanical ventilation with
      continuous postoperative positive airway pressure, was performed in all cases.
      Tracheostomy was established in three patients and pharyngostomy in two. The two
      descending necrotizing mediastinitis-Type I cases were successfully managed with
      transcervical mediastinal drainage. The descending necrotizing mediastinitis-Type
      IIA case received treatment through transcervicotomy and anterior mediastinal
      drainage through a subxiphoidal incision. The patient with descending necrotizing
      mediastinitis-Type IIB required posterior mediastinal drainage through a right
      standard thoracotomy followed by left minimal thoracotomy. CONCLUSIONS: The
      mediastinal infection, the extent of which has been accurately determined by
      computed tomograms, necessitates radical cervicotomy followed by
      pleuromediastinal drainage. Situations where infection has spread to posterior
      medisatinum, particularly when it reaches in the level of the carina (descending
      necrotizing mediastinitis-type I), may not always require aggressive mediastinal
      drainage. In comparison, diffuse descending necrotizing mediastinitis-Type IIB
      demands complete mediastinal drainage with debridement via thoracotomy.
      Subxiphoidal mediastinal drainage without sternotomy may provide adequate
      drainage in diffuse descending necrotizing mediastinitis-Type IIA.

PMID- 10077889
TI  - Therapeutic strategy of perioperative use of percutaneous cardiopulmonary bypass
      support (PCPS) for adult cardiac surgery.
AB  - SUBJECT AND METHOD: Percutaneous cardiopulmonary bypass support is beneficial for
      patients with circulatory collapse. However, therapeutic strategies of
      percutaneous cardiopulmonary bypass support for post-cardiotomy LOS have not been
      determined. We reviewed 9 patients undergoing cardiac surgery and treated with
      percutaneous cardiopulmonary bypass support to determine an adequate strategy for
      perioperative use of percutaneous cardiopulmonary bypass support. Patients
      included 8 males and 1 female with a mean age of 56.4 +/- 3.9 years. Six patients
      with IHD underwent CABG for 5 and CABG + MVR for 1 patient and 3 patients with
      valvular disease underwent AVR, AVR + MVR, and Ross operation respectively.
      Indication for percutaneous cardiopulmonary bypass support was post-cardiotomy
      LOS in 7 and preoperative cardiogenic shock in 2 patients. All patients underwent
      IABP associated with percutaneous cardiopulmonary bypass support. Systemic blood
      pressure was regulated to 100-120 mmHg by percutaneous cardiopulmonary bypass
      support flow and with minimum inotropic supports. RESULTS: Six of 9 patients
      (66.7%) were weaned from percutaneous cardiopulmonary bypass support and 5
      patients were discharged. Five of 6 patients (83.3%) with IHD were weaned from
      percutaneous cardiopulmonary bypass support compared to 1 of 3 patients (33.3%)
      (p = 0.134) with valvular disease. Hemodynamic conditions in patients weaned from
      percutaneous cardiopulmonary bypass support were markedly improved within 40
      hours of the introduction of percutaneous cardiopulmonary bypass support (mean
      percutaneous cardiopulmonary bypass support running time: 23.9 +/- 5.5 hrs). In
      contrast, those unable to be weaned from percutaneous cardiopulmonary bypass
      support (mean percutaneous cardiopulmonary bypass support running time: 84.3 +/-
      6.3 hrs) showed no improvement and developed major complications such as cerebral
      damage or multiorgan failure. CONCLUSIONS: Perioperative use of percutaneous
      cardiopulmonary bypass support may be more effective for patients undergoing
      coronary artery surgery. Limited use of percutaneous cardiopulmonary bypass
      support within 48 hours may be applicable for post-cardiotomy patients.

PMID- 10077890
TI  - Mitral regurgitation after pericardiectomy for constrictive pericarditis.
AB  - We report a case of constrictive pericarditis in which trace mitral valve
      regurgitation was detected preoperatively and temporarily worsened after a
      pericardiectomy was performed. The early postoperative data suggested that the
      increased mobility of the lateral wall, in conjunction with an increase in the
      left ventricular volume, might be one of the causes of the perioperative mitral
      valve dysfunction. The mitral valve function returned to the preoperative
      baseline thirteen months after the pericardiectomy.

PMID- 10077891
TI  - Pericardial drainage prior to operation contributes to surgical repair of
      traumatic cardiac injury.
AB  - We report on two cases of successful surgical repair of cardiac injury: one
      involving a left ventricular stab injury and the other a blunt rupture of the
      right atrium. Each patient underwent emergency surgical repair, the former via
      left anterolateral thoracotomy and the latter via median sternotomy, following
      pericardial drainage tube insertion from the subxiphoid area. The operative
      approach was chosen according to the color of drained blood, i.e., arterial
      bleeding indicated left anterolateral thoracotomy, while venous bleeding
      indicated median sternotomy. We conclude that pericardial drainage via the
      subxiphoid approach prior to induction of anesthesia is an easy and useful
      technique to perform, not only to release cardiac tamponade but to determine the
      operative approach in patients suffering from cardiac tamponade following cardiac
      injury.

PMID- 10077892
TI  - Extended radical resection for bulky N2 small cell lung carcinoma.
AB  - In three patients with bulky N2 small cell lung carcinomas who received
      chemotherapy, complete clinical remission at the N2 site was obtained. Extended
      radical resection including mediastinal lymph node dissection was performed on
      these three patients, followed by postoperative chemotherapy. Combined resected
      organs were azygos vein, superior caval vein, and left atrium. We obtained good
      results with the patients surviving 104, 53, and 38 months respectively, after
      the initial therapy.

PMID- 10077893
TI  - Intrathoracic suture abscess after lobectomy for early lung cancer.
AB  - Intrathoracic suture abscess may occur around sutures on the pleura or in the
      lung parenchyma, although it is rare to encounter such cases clinically. We
      report on a 68-year-old woman with an intrathoracic (extrapulmonary) suture
      abscess, which was discovered on a chest X-ray film one year after right-middle
      lobectomy for early lung cancer. The abscess was removed surgically, and the
      postoperative course was uneventful. Pathological examination showed that it was
      caused by braided polyester sutures.

PMID- 10077894
TI  - Proliferation of alveolar type II epithelial cells in residual lungs following
      thoracotomy.
AB  - We have found that the number of alveolar type II epithelial cells was markedly
      increased in the alveolar walls along with the visceral pleura of an excised
      residual lung in patients who had undergone an exploratory thoracotomy with
      partial lobectomy seven or nine days prior to the second thoracotomy with
      resection of the residual lung. Such increase in proliferation of alveolar type
      II epithelial cells was not found in the excised lung not exposed to a prior
      thoracotomy, and not in the excised lung exposed to a prior thoracotomy more than
      1 year before the second thoracotomy. These findings suggested that remodelling
      of the alveolar epithelial cells occurred in the residual lung in the early
      period following thoracotomy.

PMID- 10077895
TI  - Evaluation of a new laboratory test measuring plasma (1-->3)-beta-D-glucan in the
      diagnosis of Candida deep mycosis: comparison with a serologic test.
AB  - We evaluated the effectiveness of the newly developed WAKO beta-glucan test which
      measures plasma (1-->3)-beta-D-glucan concentrations in the diagnosis of Candida
      deep mycosis. This test was compared to the Cand-Tec test. The WAKO beta-glucan
      test and Cand-Tec test were performed on 212 plasma specimens which were taken at
      212 instances from 62 immunocompromised patients with serious diseases; i.e.
      hematopoietic malignancy, solid malignant tumor, etc. The sensitivities and
      specificities for the WAKO beta-glucan test were 84.8 and 85.9%, respectively,
      and 60.9 and 80.0% for the Cand-Tec test.

PMID- 10077896
TI  - [Antagonistic interaction between Clostridium butyricum and enterohemorrhagic
      Escherichia coli O157:H7].
AB  - Antagonistic interaction between Clostridium butyricum strain MIYAIRI 588 and
      enterohemorrhagic Esherichia coli (EHEC) strain O157:H7 006 was examined using
      streptomycin-treated SPF mice and germ free mice. All SPF mice pretreated with
      streptomycin were colonized with EHEC O157:H7. On the other hand, only 20% of the
      SPF mice pretreated with streptomycin and C. butyricum were colonized with EHEC
      O157:H7. In addition, germ free mice died within 4-7 days after infection with
      EHEC O157:H7. In contrast, all gnotobiotic mice mono-associated with C. butyricum
      survived after the challenge with EHEC O157:H7. Both the number of EHEC and the
      amounts of shiga-like cytotoxin (SLT, type 1 and type 2) in fecal contents of
      gnotobiotic mice treated with C. butyricum were less than those of mice infected
      with only EHEC O157:H7. In conclusion, the probiotic bacterium, C. butyricum
      strain MIYAIRI 588, has a preventive effect against EHEC O157:H7 infection.

PMID- 10077897
TI  - [Resuscitation from the viable but nonculturable state of Helicobacter pylori].
AB  - It is well known that the change of state from the culturable to not culturable
      on pathogenic organisms could easily occurred. These states of bacteria were so
      called viable but nonculturable (VNC). The coccoid form of H. pylori is seems to
      be in this state. The possibility of resuscitation of H. pylori was examined in
      vitro. The coccoid form bacteria was treated with Ammonium Sulfate and heat shock
      before culture, and cultured in Brucella broth containing, sodium pyruvate, laked
      human erythrocyte and serum. The growth of the rod spiral form was found in the
      coccoid form bacteria, and further the bacteria could grow on blood agar and
      Skirrow agar as well as the original strain. It was strongly suggested that the
      resuscitation from VNC state of cells to culturable form consists of two
      processes, stimulation and supplemented of appropriate nutrition.

PMID- 10077898
TI  - [Isolation of Shiga toxin-producing Escherichia coli O157:H7 from processed
      salmon roe associated with the outbreaks in Japan, 1998, and a molecular typing
      of the isolates by pulsed-field gel electrophoresis].
AB  - Shiga toxin-producing Escherichia coil (STEC) O157 were isolated from processed
      salmon roe which had been a suspected food item in sporadic infections which
      occurred in Japan in 1998. A total of 45 samples of the processed salmon roe were
      pre-enriched in trypticase soy broth (TSB) at 36 degrees C for 6 h and novobiocin
      supplemented modified EC broth (mEC-NB) at 42 degrees C for 18 h. After the pre
      enrichments, the cultures were examined for possible occurrence of STEC O157,
      using an immunomagnetic separation (IMS) method. From the examination, a total of
      84 strains of STEC O157:H7 that were positive for both stx 1 and stx 2 genes were
      isolated. By applying the most-probable-number technique, it was estimated that
      the number of STEC O157 was in the range of 0.73-1.5 per 10 g of the processed
      salmon roe. Subsequent analysis of the isolates by a pulsed-field gel
      electrophoresis (PFGE) revealed a pattern commonly seen in 82 isolates and
      another pattern in two isolates. Clinical isolates from 7 patients also showed an
      identical pattern to those of the 82 isolates and one isolate from a patient
      showed the other pattern identical to those of the two isolates. The isolates
      were found to belong to the phage type 14.

PMID- 10077899
TI  - [Studies on detection methods for Legionella species from environmental water].
AB  - We investigated selective cultivation media and previous treatments of samples
      suitable for detection of Legionella species from environmental water and for
      elimination of co-existing microbes which gave rise to an interference with the
      evaluation of Legionella sp. growth. Twenty thousand U of polymyxin B (PL-B)/ml
      and 100 micrograms of oxytetracycline (OTC)/ml seem to be useful as additives to
      MWY selective agar medium. Both antibiotics markedly inhibited the growth of co
      existing microbes with almost no influence on the growth of Legionella sp. In the
      studies on the resistance of 8 strains of Legionella sp., 24 strains of co
      existing microbes and 2 standard strains of Staphylococcus aureus and Escherichia
      coli to acid treatment (0.2 M HCl-KCl, pH 2.2, 25 degrees C, 4 minutes) and
      heating (50 degrees C, 20 minutes), acid treatment or heating alone showed no
      inhibition on the growth of almost all strains examined. However, combination
      with acid treatment after heating resulted in an apparent extinction of almost
      all microbes except for Legionella sp., Seven strains from co-existing microbes
      showed an apparent growth inhibition against 8 strains of Legionella sp. with
      different serotypes and were all identified as Pseudomonas aeurginosa, which were
      all eliminated by means of the combination with acid treatment after heating.
      From these results, it was concluded that the combined pre-treatment of water
      samples with acid after heating and the addition of PL-B and OTC into the
      selective cultivation medium is an useful method for detection of Legionella sp.
      from environmental water.

PMID- 10077900
TI  - Serotypes of human rotaviruses in 7 regions of Japan from 1984 to 1997.
AB  - Human rotavirus (HRV) serotypes were studied from diarrheal stool specimens in
      children in 7 regions of Japan (Sapporo, Tokyo, Maizuru, Osaka, Kagawa, Kurume,
      and Saga) from 1984 to 1997 by enzyme immunoassay (EIA) with serotype-specific
      monoclonal antibodies against serotypes 1, 2, 3, and 4. In addition, reverse
      transcription-polymerase chain reaction (RT-PCR) was conducted for analysis of
      "others" which included nonserotypable and mixed-serotype rotavirus specimens by
      EIA. In 3756 rotavirus-positive specimens, serotype 1 was detected in 2649
      (70.5%), serotype 2 in 362 (9.6%), serotype 3 in 232 (6.2%) and serotype 4 in 196
      (5.2%). Overall, serotype 1 was predominant from 1984 to 1997, although there
      were a few cases in which serotype 2, 3 and 4 became predominant based on area
      and year. The frequency of serotype 1 has gradually increased since 1993. Twenty
      two, 2, 3 and 1 among 57 specimens of "others" by EIA from Tokyo, Maizuru,
      Sapporo and Kurume in 1995-1996 and 1996-1997 were determined as serotypes 1, 2,
      3, and 9 by RT-PCR, respectively.

PMID- 10077901
TI  - [Evaluation of a multi-hospital cooperative study on the efficacy and safety of
      panipenem/betamipron (PAPM/BP) on elderly patients of respiratory infections].
AB  - The efficacy and safety of Panipenem/Betamipron (PAPM/BP) on elderly patients of
      respiratory infections was examined at 17 hospitals in a cooperative study. Among
      the 95 case, we examined the efficacy of the medication in 86 cases, and the
      safety in all 95 cases. Efficacy was confirmed in 81.3% of pneumonia patients,
      57.7% of secondary-infection patients of chronic respiratory diseases, and 74.4%
      of the total. No significant difference was observed among each group according
      to age, comparing patients > or = 65 years old grouped by 5 years, or when
      broadly comparing groups < 75 years and > or = 75 years of age. The
      microbiological efficacy was 100% for Streptococcus pneumoniae, 80% for
      Staphylococcus aureus, 80% in Klebsiella pneumoniae; therefore, a very good
      disappearance rate of symptoms could be obtained in all major respiratory
      etiologic agents except Pseudomonas aeruginosa. In this study, we also examined
      other factors considered to affect the course of treatment for elderly patients
      of infectious diseases, namely the presence of absence of underlying diseases,
      the distinctness of infectious symptoms, the patient's condition before the
      appearance of infectious symptoms, and previous history of treatment with
      antimicrobial agents. For safety, the incidence rate of side effects was 14.7%,
      which was similar to the 16.9% in the developmental study. These two findings
      were also similar in content. No significant difference was observed among each
      age group, comparing patients > or = 65 years old grouped by 5 years, or
      comparing groups < 75 years and > or = 75 years of age. From the above
      evaluation, we consider PAPM/BP to be an effective drug for normal adult patients
      as well as elderly patients of respiratory infections.

PMID- 10077902
TI  - [Comparison of O-serotype distribution of Escherichia coli isolated from faecal
      specimens of patients with sporadic diarrhea and healthy persons and regional
      difference in Japan].
AB  - To investigate the isolation frequency of O-serotype of Escherichia coli, a total
      of 1,563 faecal specimens obtained from patients with sporadic diarrhea in
      Ishikawa between July 1997 and June 1998, were examined. As a result of O
      serotyping of isolated strains using commercially E. coli antisera (43 different
      types), 247 strains of 29 different O-serotypes were isolated. Isolation rate was
      15.8%. Most predominant O-serotype was O1 (128 strains, 52%), followed by O18 (26
      strains, 11%), O6 (17 strains, 7%), O111 (16 strains, 6%), and these 4 different
      O-serotypes took up three quarters of the isolated E. coli. Between August 1996
      and May 1997, E. coli isolation from faecal samples of 51,893 healthy persons and
      O-serotyping of isolated strains using commercial antisera to 6 predominant O
      serotypes (O-26, 111, 114, 128, 157 and O1) of VTEC/EHEC were carried out. Among
      6 O-serotypes, the most predominant O-serotype was O1 (93% of isolates), followed
      by O26, 111, 128 (6%) and O114, 157 (1%). These isolation frequencies in patients
      were 80%, 18%, 2%, respectively, have resembled each other in healthy persons in
      many points. In a similar way, of these distributions of O-serotype of strains
      hemolysed on Beutin's blood agar plates, we compared patients with healthy
      persons. Fifty-six strains (3.6% of the total) of E. coli of different O
      serotypes were isolated from 1,563 patients and 57 strains (2.8% of the total)
      belonging to 11 serotypes from 2,036 healthy persons. As a result of O-serotype
      frequency, both groups resembled each other. O18 and O6, the most predominant O
      serotypes, occupied 64% of the isolated strains in patients and 74% in healthy
      persons. Next in patients, O1, 26 were 7%--level, O28 ac, 152, 157 were 4%-
      level, respectively, and in healthy persons. O1 was 5%--level, O28 ac, 55, 146,
      152 were 4%--level respectively. In the comparison of O-serotype frequency of E.
      coli isolated from sporadic diarrhea in other 5 areas (Kanto district, Tokyo,
      Oita, Aichi and Ishikawa), O1, 6, 8, 18, 25, 26, 55, 86a, 111, 125, 126, 127a,
      128, 146, 148, 157 and 166 (17 types) have covered a wide area. On the other
      hand, O29, 44, 78, 112ac, 115, 136, 143, 152, 168 and 169 (10 types) have a
      tendency to distribute in local areas, we believe that there are regional
      differences even in the same Japanese territory.

PMID- 10077903
TI  - [An analysis of fever of unknown origin defined by newly proposed practical
      criteria. A prospective study of 56 cases].
AB  - The criteria proposed by Petersdorf has been in use internationally to define the
      fever of unknown origin (FUO) since 1961 and the research of FUO has progressed
      with this criteria. Mean-while, new diagnostic methods have been developed and
      illness behavior of febrile patients has changed considerablly. Accordingly, the
      definition by Petersdorf is becoming less matched to current clinical situation.
      Therefore, we have developed a new practical criteria of FUO; i.e., out-patients
      who are febrile more than 2 weeks, documented temperature higher than 37.5
      degrees C at least on one occasion and undetermined diagnosis and in-patients who
      are febrile more than 1 week with documented temperature higher than 37.5 degrees
      C, and undetermined diagnosis. Between October 1, 1993, and October 31, 1996, we
      prospectively collected a series of febrile patients who fulfilled our new
      criteria. We identified 56 patients by our criteria (23 male and 33 female, age:
      49.7 +/- 20.6. range 15 to 88). Of this 56 patients, 19 (32%) were found to have
      infections, 18 (31%) had collagen disorders, 5 (9%) had malignancy and 6 (10%)
      had died. Of 56 patients, 38 (68%) were in the newly added group. Of these 38
      patients, 4 patients had subacute necrotizing lymphoadenitis, 4 cytomegalovirus
      infection, 3 polymyalgia rheumatica, 3 tuberculosis. Four patients (10%) died.
      With our criteria, febrile patients who previously had not been included were
      found to have as poor a prognosis as with the Petersdorf group.

PMID- 10077904
TI  - [Multicenter screening of Chlamydia pneumoniae pneumonia by ELISA method].
AB  - We prospectively investigated the etiology of community-acquired pneumonia among
      adult patients admitted to three general hospitals over one year. Antibody titers
      to Chlamydia pneumoniae were also measured by ELISA method to investigate the
      incidence and clinical pictures of C. pneumoniae pneumonia in Japan. Two hundred
      and fourteen patients were enrolled in the study. Seventeen patients (7.9%)
      satisfied the criteria for diagnosis of acute infection due to C. pneumoniae by
      ELISA method. C. pneumoniae was the 3rd leading causative agent following
      Streptococcus pneumoniae (21.5%) and Haemophilus influenzae (8.4%). Preexisting
      antibodies were detected in 62.1% of the patients. Most of the patients with C.
      pneumoniae pneumonia were aged, and had comorbidities of respiratory system.
      Superinfection with bacterial pneumonia was recognized in some patients. Though
      there are several problems, ELISA method is thought to be useful to diagnose C.
      pneumoniae pneumonia, and is suitable for screening tests.

PMID- 10077905
TI  - [Imported trichinellosis with severe myositis--report of a case].
AB  - A 38-year-old Japanese male who had traveled in China from September 13 to
      October 5, 1997, developed fever and severe conjunctivitis from October 20. After
      he was hospitalized in Kyoto City Hospital for persistent high fever on October
      29, he developed muscular weakness and dysphagia which continued for two weeks.
      An electromyogram showed a myogenic pattern, and laboratory findings showed
      significant elevation of serum enzyme levels of muscle origin: CPK, 3,095 IU/l;
      aldorase, 195 IU/l; myoglobin, 7,570 ng/ml, and myoglobinuria, 94,700 ng/ml. The
      WBC was 10,800/microliter with 45% eosinophils. Muscular biopsy showed
      degeneration of muscle fibers with infiltration of macrophages and lymphocytes.
      On further inquiry, it was revealed that the patient had eaten smoked bear meat
      in China on September 30, three weeks prior to the onset of symptoms. A dot-ELISA
      serologic test for parasites was positive for Trichinella. Further, a coiled 1.2
      mm long Trichinella larve was recovered from approximately 100 mg of frozen
      biopsied muscle by an enzyme digestion method. Mebendazole was given to the
      patient at a dosage of 200 mg/day for seven days. CPK levels were normalized
      within 3 days of the beginning of the treatment, and he was discharged without
      any symptoms. Physicians must be aware of trichinellosis and should include it in
      their differential diagnosis when examining patients with myositis and
      eosinophilia of unknown origin.

PMID- 10077906
TI  - [Plasmodium falciparum infection in a 8-year old boy].
AB  - A 8-year old Japanese boy who returned from Tanzania was admitted to our hospital
      because of fever, vomiting, and headache. He was diagnosed as a Plasmodium
      falciparum infection verified by a blood smear. He was treated with quinine and
      halofantrine, and recovered completely. Malaria infection should be considered
      when patients return from Malaria endemic areas.

PMID- 10077907
TI  - [Campylobacter fetus bacteremia and thrombophlebitis in a patient with
      Waldenstrom's macroglobulinemia].
AB  - We report a 67-year-old male with Waldenstrom's macroglobulinemia who developed
      Campylobacter fetus subspesis fetus (C. fetus) bacteremia and thrombophlebitis.
      The patient developed a fever and pain in his left lower limb, and could not walk
      because of the pain. Radioisotopic venography showed thrombophlebitis in his left
      lower limb. His blood culture grew C. fetus. After starting intravenous PAPM/BP,
      his symptoms resolved promptly. In contrast to Campylobacter jejuni which is a
      common cause of infectious diarrhea, C. fetus infection has distinct clinical
      features showing systemic illness such as bacteremia and thrombophlebitis mainly
      occurring in immunocompromized patients. This organism should be considered as
      one of the possible pathogenes in the infectious complications of the
      immunocompromized patients.

PMID- 10077908
TI  - [Prevalence of serum IgG antibody against Bartonella henselae in an asymptomatic
      Japanese population].

PMID- 10077909
TI  - [The surgical treatment of pancreatic pseudocyst].
AB  - Experience of surgical treatment of 370 patients with chronic pancreatitis,
      complicated by pancreatic pseudocyst occurrence, was analysed. Differentiational
      approach to operative intervention permitted to reduce the frequency of
      conduction of resections by 21.5%, replacing them by enhancing the quantity of
      drainage operations, what permitted to lower the occurrence of postoperative
      complications and to improve late follow-up result of treatment.

PMID- 10077910
TI  - [The combined treatment of cholangitis in patients with intraoperative damage and
      posttraumatic cicatricial stricture of the extrahepatic bile ducts].
AB  - The result of treatment of 196 patients with cholangitis, occurred due to
      intraoperative trauma and posttraumatic cicatricial stricture of extrahepatic
      biliary ducts (EBD) was analysed. Methods of extracorporeal detoxication
      hemosorption (in 53 observations), plasmapheresis (in 32), biohemosorption (in
      21) were applied in the complex of treatment. The EBD decompression was conducted
      using endoscopic diathermocoagulation and bougienage of cicatricial stricture (in
      56 patients) with introduction of a hidden drain (in 9) or nasobiliary catheter
      (in 47). In all the patients reconstructive and restorative operations were
      conducted. Postoperative complications occurred in 43 (22%) patients, 31 (15.8%)
      patients died. Stricture recurrence, necessitated reoperation conduction, was
      noted in 15 (7.6%) patients.

PMID- 10077911
TI  - [Portal hemodynamics, collateral venous circulation and encephalopathy in
      patients with esophageal and gastric varices in liver cirrhosis].
AB  - Complex hemodynamic investigations were conducted in 166 patients with liver
      cirrhosis and syndrome of portal hypertension. It was established that gastric
      varicose veins (VV) in 40% of observations are connected with v. renalis sin. by
      means of gastrorenal shunts (GRS), esophageal VV in 16.9% of observations--with
      v. renalis sin. Gastric VV frequently are connected with large GRS. More the GRS
      diameter, the more pronounced lowering of volemic blood flow in portal vein
      occurs. While gastric VV presence the volemic blood flow value in portal vein
      significantly lesser than while isolated esophageal VV. Encephalopathy occurs
      more frequently in patients with GRS, flowing into v. renalis sin. than in
      patients while other collateral blood flow ways present. Reverse dependence was
      revealed between GRS diameter and the degree of portal vein pressure lowering.

PMID- 10077912
TI  - [The late results of deportalization of the pancreatic blood flow in patients
      with type-1 diabetes mellitus].
AB  - Late follow-up result of the pancreatic blood flow deportalization using distal
      splenorenal anastomosis conduction in 16 patients with type-I diabetes mellitus
      was studied up. The diabetes mellitus course stabilization was promoted by
      performance of operation.

PMID- 10077913
TI  - [The indications for performing diagnostic and therapeutic laparoscopy in
      emergency surgery on the abdominal organs].
AB  - In 1352 patients with urgent diseases and traumatic injuries of the abdominal
      cavity organs laparoscopy was conducted. Diagnostic authenticity of method is
      96.5%. Indications to remedial laparoscopy, conducted in 47.4% of patients, were
      rendered concrete and broadened. An acute inflammation was eliminated in 95.3% of
      patients, which were operated on according to the indications in a "cool period",
      104 (7.5%) of patients died.

PMID- 10077914
TI  - [Lipid peroxidation and the function of the antioxidant system in sepsis in
      patients with soft-tissue suppurative and inflammatory lesions].
AB  - While sepsis present in 73 patients with purulent-inflammatory affection of soft
      tissues and in 76 patients with local purulent inflammation the dynamics of
      processes of peroxidal oxidation of lipids (POL) and of antioxidant system (AOS)
      was studied up. In patients of both groups the trustworthy increase of the POL
      products in a blood plasma and pre- and postoperative AOS suppression was noted.

PMID- 10077915
TI  - [The state of and ways to improve diagnostic efficacy in the main forms of
      malignant neoplasms].
AB  - The state of diagnosis of malignant tumors in Ukraine concerning the indexes of
      opportunity, activity, accuracy was analysed. Complex of measures for an early
      detection of oncologic patients in all ranks of medical-sanitary aid to
      population was proposed.

PMID- 10077916
TI  - [The use of laser spectroscopy of the blood plasma for selecting rectal cancer
      patients with a colostomy for the performance of a restorative operation].
AB  - The blood plasma changes were studied up in 37 patients, to whom Hartmann
      [correction of Gartman] operation was conducted for cancer of recti, using the
      laser correlational spectroscopy (LCS) method. In 22 patients the LCS data did
      not differ of such in healthy persons. In these patients the reconstructive
      operation on colon was conducted. In 12 patients the LCS data were characteristic
      for cancer of recti. Of them in 5 the progress of the disease was noted while
      laparotomy conduction and in 6--one year after the colonic continuity
      restoration.

PMID- 10077917
TI  - [Intensive therapy in burns and carbon monoxide poisoning].
AB  - While treatment conduction of 38 patients with severe burns and poisoning with
      carbonic oxide in complex of antishock measures there was applied a nondirect
      electrochemical oxidation of blood and internal laser irradiation of blood. There
      was used He-Nd laser. The mortality lowering by 3.3 times in comparison with 40
      patients, in whom the traditional intensive therapy was applied, was noted.

PMID- 10077918
TI  - [The surgical treatment of deep burns in the course of the 1st week after the
      trauma].
AB  - Results of treatment of 252 patients with burns, to 138 of whom an early
      necrectomy in terms from several hours to 7 days was conducted, are adduced.
      Surgical concept of discrimination of the excised deep burn wounds of III and IV
      degrees according to the depth of affection, using the organ-preserving tactics
      in dependence of functional state and the cutaneous and fascial wound coverage
      safety, was proposed. The operative treatment tactics choice depending on
      indications and contraindications for securing of successful treatment of deep
      burns was discussed.

PMID- 10077919
TI  - [The x-ray diagnosis of the respiratory distress syndrome].
AB  - In 210 injured persons with severe nonthoracic trauma the roentgenological
      changes were studied up. Three stages of changes, characteristic for the
      respiratory distress-syndrome were revealed.

PMID- 10077920
TI  - [The use of early operations for esophageal burns].
AB  - The experience of treatment of 278 patients with oesophageal burns is summarized.
      Before the oesophagoplasty conduction 52 operations were performed.

PMID- 10077921
TI  - [Combined lesions of the chest and abdomen].
AB  - The structure of combined thoracic and abdominal trauma was analysed in 500
      injured persons for 1984-1994 period. Mortality in the open trauma was 13.4% and
      in the closed one--20.4%.

PMID- 10077922
TI  - [The effect of the patient's hormonal status on the outcome of an operation for
      stomach cancer].
AB  - The comparative analysis of the blood serum contents of triiodthyronine (T3),
      thyroxin (T4), hydrocortisone, prolactin and insulin in 59 survived and in 13
      dead patients with gastric cancer was conducted. The prognostical significance of
      hormonal stress disorders was revealed. The prognosis for gastric cancer patients
      while the anabolic processes suppression is nonfavourable.

PMID- 10077923
TI  - [An evaluation of the immediate results of performing esophagogastroplasty].
AB  - The results of oesophageal resection with one-staged oesophagogastroplasty were
      studied up in 108 patients. The mechanical suture failure occurred in 12 (16.4%)
      of 73 patients, after the manual-forming anastomosis conduction this complication
      did not occur. The method of the anastomosis forming using one-raw manual suture
      with plication by anterior gastric wall proved to be the most secure one.
      Application of this method together with prophylaxis of thromboembolic and
      respiratory disorders have permitted to reduce mortality by 2.5 times.

PMID- 10077924
TI  - [The use of a portable CO2 laser in thoracic surgery].
AB  - The results of the thoracic operations conduction using a portable CO2 laser LST
      20/01 in 93 patients were analyzed. The advantages and shortages of the laser
      technique are noted.

PMID- 10077925
TI  - [The carotid sinus syndrome: problems and outlook].
AB  - Electrocardiostimulator was implanted in 108 patients for the carotid sinus
      syndrome. In 38 observations ventricular stimulation was applied, in 19--the two
      chamber one and in 51--the atrial. The syncope disappearance was observed while
      the DDD and AAI modes of stimulation. If the atrioventricular conduction disorder
      do not occur while doing transoesophageal stimulation of left atrium during the
      provocation tests the atrial stimulation is indicated.

PMID- 10077926
TI  - [The use of the upper septal approach during the performance of operations on the
      left atrioventricular valve].
AB  - The upper septal access to left atrioventricular valve (LAVV) was applied while
      the operation conduction, using the heart-lung apparatus, in 7 patients.
      Excellent exposition of all the parts of the LAVV ring and of subvalvular
      apparatus was achieved in all observations. There were no observed significant
      rhythm disorders and other complications due to the access chosen.

PMID- 10077927
TI  - [The principles of treating the traumatic disease in multiple injuries].

PMID- 10077928
TI  - [Is diuretic-resistant ascites reversible in patients with liver cirrhosis amd
      portal hypertension?].

PMID- 10077929
TI  - [The use of computed tomography in the diagnosis of cholelithiasis].

PMID- 10077930
TI  - [A case of an isolated injury to the hepatic artery proper].

PMID- 10077931
TI  - [Borys Andriievs'kyi (on the centenary of his birth)].

PMID- 10077932
TI  - [Significance of duodenal stasis in the etiology of recurrent hemorrhage in
      duodenal ulcer].
AB  - In 92 patients the influence of duodenostasis on possibility of occurrence of
      rehemorrhage from duodenal ulcer was studied. It was established that the
      heightened risk of rehemorrhage is promoted by disorders of motility, blood flow
      and acid production.

PMID- 10077933
TI  - [Morphological changes in the stomach and duodenum in ulcer disease with
      Helicobacter infection].
AB  - In 119 gastroduodenal ulcer disease (UD) patients the presence of Helicobacter
      pylori (HP) was determined and the morphological changes of gastric mucosa were
      studied up. The rapid test with urease, cytological investigation of the smear
      prints and histological examination of the operational material biopsies were
      done for the HP elimination detection. In gastric UD with nonsignificant HP
      dissemination the mucosal morphological changes are limited mainly by the cell
      infiltration of various degree. While the duodenal UD observation, as a rule,
      there were revealed the HP dissemination of the III-IV degree and significant
      morphological changes, extended in deep layers of gastric wall, stroma,
      significant dystrophic and necrobiotic processes in superficial layer.

PMID- 10077934
TI  - [Effectiveness of the use of solcoseryl after surgery of acute hemorrhage in
      gastroduodenal ulcer].
AB  - The experience of solcoseryl application in 70 patients, operated on for an acute
      hemorrhage from gastroduodenal ulcer, was summarized. The preparation was
      injected intravenously in the dose of 10 ml in 5% solution of glucose every other
      day during 6 days and then in the dose of 5 ml intramuscularly during 4-5 days.
      High efficacy of solcoseryl, manifesting by more earlier elimination of pain and
      oedema, healing of mucosa by first intention, shortening of the treatment
      duration in stationary by 3-5 days, was established.

PMID- 10077935
TI  - [Transcutaneous electric stimulation of the liver and bile ducts during active
      enterosorption in combined surgical treatment of obstructive jaundice of
      nontumorous etiology].
AB  - The influence of transcutaneous electrostimulation of liver and biliferous ducts
      while conduction of desintoxication using chitinous enterosorbent "Mikoton" on
      the result of treatment of hepatargy in patients with obstructive jaundice of
      nontumoral genesis in the early postoperative period was studied.

PMID- 10077936
TI  - [Performance of simultaneous operations in surgery].
AB  - The experience of conduction of simultaneous operations in 183 patients is
      summarized. The indications and advantages of their application are
      substantiated.

PMID- 10077937
TI  - [Carcinosarcoma: a rare mixed tumor of the bronchopulmonary system].
AB  - Six patients with carcinosarcoma were observed in the clinic. In 4 patients with
      roentgenological signs of tumor were determined and in 2--the signs of pleuritis.
      The diagnosis was established after pulmonary resection performance or after
      thoracoscopy with pleural biopsy conduction.

PMID- 10077938
TI  - [Trans-sternal method of performing extended pulmonectomy in left-sided
      bronchopulmonary cancer].
AB  - The method of the extended pulmonectomy conduction using transsternal
      transpericardial-mediastinal access to left main bronchus and pulmonary artery
      instead of intercostal one was depicted.

PMID- 10077939
TI  - [Perforation of gastric fundus ulcer into the pleural cavity after performance of
      pneumonectomy].
AB  - The results of 3 observations concerning the gastric fundus ulcers penetration
      into the pleural cavity after pulmonectomy conduction are adduced.

PMID- 10077940
TI  - [Accuracy of the term "diabetic angiopathy of the lower limbs". II. Possibilities
      of the morphological assessment of the stage of diabetic angiopathy of the lower
      limbs and the choice of treatment tactics].
AB  - In 40 patients with diabetic angiopathy of lower extremities of terminal stage
      the foot tissue biopsies were studied up using electron and light microscopy. A
      skin was supposed to be most acceptable substrate for biopsy because there was
      established morphological changes of tissues, occurring in a single direction and
      in a single type. Morphological criteria of the angiopathy stages were
      delineated, permitting to make a differentiative choice of the treatment tactics.

PMID- 10077941
TI  - [Analysis of mortality of injured persons with isolated and multiple trauma].
AB  - The causes of death of 192 injured persons with isolated or combined trauma were
      analyzed.

PMID- 10077942
TI  - [Use of a composite organic biosilicone sorption preparation imosdinit in the
      treatment of anaerobic infections in surgery].
AB  - New application sorbent on the base of hydrogel and xerogel of methylsilicone
      acid with immobilized nitazole in connection with dimexide- imosdynit was
      investigated in experiment. High efficacy of imosdynit in the treatment of
      clostridial and non-clostridial anaerobic infection, caused by Klebsiella, was
      established. Proteus and blue pus bacillus are nonsensitive to imosdynit.
      Preparation was applied in 56 patients with purulent peritonitis. The frequency
      of wounds suppuration reduced by 2.4 times.

PMID- 10077943
TI  - [Long-term results of the treatment in complicated forms of acute paraproctitis].
AB  - The surgical treatment results of 260 patients with complex forms of an acute
      paraproctitis in terms from 6 mo to 9 yrs are adduced. After radical operation
      excellent and good result was noted in 78.7% of patients, poor--in 15.3%; after
      nonradical one--in 7.8 and 92.2% accordingly. After the internal fistula aperture
      closure using translocated flap of the distal rectum mucosa in 95.9% of patients
      an excellent and good result was achieved, poor--in 2%; after opening of abscess
      with cryptectomy--in 80.6 and in 17.9% accordingly; after the ligature method
      application--in 55.9 and in 29.5% accordingly.

PMID- 10077944
TI  - [Substantiation of complex surgical treatment of inguinal hernia in children
      based on pathogenetic criteria].
AB  - Method of complex surgical treatment of inguinal hernia in children, basing on
      the early conduction of surgical correction of pathology, application of
      microsurgical technique of the operation conduction, using of pharmacologic
      defense of hematotesticular barrier and medicinal therapy of the man sexual gland
      ischemia, was elaborated and substantiated.

PMID- 10077945
TI  - [Classification of thyroid gland operations].
AB  - Classification of operations on thyroid gland depending on the tissue volume
      preserved and basing on the analysis of surgical treatment of more than 2000
      patients was presented. Substantiation and characteristics of its headings
      permits to take into account the intervention volume, what is peculiarly
      important during the automatized processing of large masses of information.

PMID- 10077946
TI  - [Use of intestinal plasty in ureterohydronephrosis].
AB  - One-sided and two-sided intestinal plasty was conducted in 217 patients for
      congenital and acquired diseases of ureters. Preoperative and intraoperative
      visual diagnosis of the ureteric wall changes extent is imperfect and causes a
      majority of poor results in ureterocystoneostomy. Diagnosis was improved,
      indications were specified for application of intestinal ureteric plasty for
      achalasia, ureteric hypoplasia, megaureter, ureterohydronephrosis, while initial
      sufficient kidney function present.

PMID- 10077947
TI  - [Substantiation of the use of implantation method in surgical reinnervation of
      kidney transplant].
AB  - New operative method of surgical reinnervation of transplanted kidney was
      elaborated, experimentally substantiated on 39 mongrel dogs and used in 26
      recipients of allonephrotransplants in three transplantation centres. The
      efficacy and security for recipient of the proposed combined implantation in
      sinus of transplanted kidney of atraumatically mobilized iliac vegetative
      plexuses consisting of fascia-adventitia strip-like flaps and lower hypogastric
      nerves of recipient zone with the neuroterminals preserved was noted. The method
      may be used independently and in combination with method of
      nephrogangliotransplantation.

PMID- 10077948
TI  - [Homeopathic therapy of chronic prostatitis in participants of the Chernobyl AES
      accident clean-up].
AB  - An accident on the Chernobyl Atomic Power Station (CHAPS) caused unprecedented
      ecological catastrophe and the problems of studying of the ionizing radiation
      action on human organism appeared. Irradiation causes occurrence of local
      reactions in prostatic gland. The efficacy of complex homeopathic remedies
      produced by firm "Heel" is established in the treatment of chronic prostatitis in
      participants of an accident liquidation on the CHAPS.

PMID- 10077949
TI  - [Hemodynamic changes in the liver, kidney, small intestine and pancreas in
      experimental acute pancreatitis].
AB  - In an acute experiment on dogs using methods of hydrogen clearance detection and
      polarography it was established, that in early stages of an acute pancreatitis
      vasoconstriction occurs in pancreas, liver, kidneys, small intestine, changing
      into vasodilatation, accompanying by the tissues hypoxia.

PMID- 10077950
TI  - [Functional state of the pancreas and risks of occurrence of acute pancreatitis
      in early use of enteral tube feeding in surgery of bile ducts].
AB  - In experiment on 43 dogs while the loading with polysubstrate food mixtures it
      was established, that the food passage shunting and starvation enhances the
      incretory answer value, but cholestasis and starvation lowers the pancreatic
      secretory potency. The restorational operation conduction promotes elimination of
      the cholestasis influence, but aggravates the action of starvation. An acute
      pancreatitis was not noted.

PMID- 10077951
TI  - [Correction of bile outflow in patients with acute cholangiogenic pancreatitis].

PMID- 10077952
TI  - [Endoscopic interventions as an alternative to reconstructive operations in
      postcholecystectomy syndrome].

PMID- 10077953
TI  - [The ecological, taxonomic and biotechnology aspects of research on bacteria and
      higher plants that produce biologically active substances].
AB  - The paper deals with the basic results of scientific activity of the Department
      of Antibiotics at the Institute of Microbiology and Virology of the National
      Academy of Sciences of Ukraine for the last two decades. Results of fundamental
      ecological and taxonomical investigations of bacteria of the Pseudomonas and
      Bacillus genera, study of regularities in formation of antibiotics and other
      biologically active substances by microorganism of these taxa and by higher
      plants have been presented; new antibiotics, probiotics and other biopreparations
      developed at the Department during this period have been characterized.

PMID- 10077954
TI  - [The taxonomic position, ecological aspects and physiological-biochemical
      characteristics of microorganisms having industrial importance].
AB  - The paper presents fundamental results of the investigations obtained in the
      Department of Physiology of Industrial Microorganisms at the Institute of
      Microbiology and Virology of the National Academy of Sciences of Ukraine for the
      recent 15-20 years, as well as the Department developments directed to creation
      of biotechnological preparations, products and processes, most of which have been
      put into practice of the national economy and health protection. Data have been
      presented concerning the study of systematics, biology and ecology of
      nocardioform and coryneform bacteria, lactic acid bacteria and yeasts. When
      studying physiological-biochemical peculiarities and biological effect of the
      studied microorganisms, considerable attention has been paid to growth physiology
      of lactic acid bacteria, yeasts, lectin-forming bacteria, to processes of shaping
      of fungal mycelium under the conditions of batch cultivation as well as to
      microorganisms which take part in sewage treatment for heavy metals and oil
      products. The work also deals with the problems of creation and application in
      the economy of preparations intended for treatment and prophylaxis of gastro
      intestinal diseases of cattle, poultry and swine, for siloing fodder, of new
      lactic acid preparations of functional direction, technological grounds of sewage
      treatment for oil products and six-valent toxic chrome.

PMID- 10077955
TI  - [The genetics and selection of microorganisms].
AB  - Results of investigations in genetics and selection of bacteria, streptomycetes
      and fungi obtained at the Department of Genetics of Microorganisms for the recent
      35 years are presented in the review.

PMID- 10077956
TI  - [Natural interferons: the methods of their isolation, the properties and
      characteristics of the preparations and their use in animal infections].
AB  - Data of studies carried out in the field of interferonology during the last 20
      years which are based on the proposed new biotechnologies for production of
      natural alpha- and gamma-interferons (IFNs) have been analyzed. "Know-how" of
      these technologies consists in the usage of non-traditional source (spleen
      instead of blood) for preparing the suspension of immunocytes--producers of
      preparations, in introduction of the stage of "coinduction" when producing alpha
      IFNs, use of bacterial lectins of apathogenic bacilli as inducers of gamma-IFN
      genesis. It was shown, that in vitro and in vivo the both types of preparations
      several times increased both absorbing and bactericidal activity of phagocytes of
      swine and cattle peripheral blood, 3-5 times increased antibody genesis in
      animals after their immunization by colibacteriosis vaccine. It was proved that
      immunomodulating ability of alpha-IFNs is significantly (3-5 times) higher than
      that for gamma-IFNs. In non-purified preparations of IFNs the fractions have been
      discovered which had antibacterial and antitoxic action of wide spectrum of
      specificity. Both preparations were effective for prophylaxis and therapy of not
      only viral, but also bacterial infections in animals: transmissive
      gastroenteritis of swine, parainfluenza of calves, colibacteriosis of pigs and
      calves, etc., and promoted the increase of animals productivity by 20-35%. If
      under hemoblastosis alpha-IFN caused remission, they could be effectively treated
      using homologous gamma-IFN.

PMID- 10077957
TI  - [The molecular biological mechanisms of the functioning of microbial
      glycopolymers and carbohydrases].
AB  - Special attention has been paid to glycopolymers which perform various functions
      in the microbial cell, determine its interaction with the environment, possess a
      broad range of biological activity (antigenicity, cytotoxicity, immunomodulating
      properties, participation in the bean-rhizobial symbiosis). Composition and
      structure of the following polysaccharides, lipopolysaccharides and their
      components: O-polysaccharide, core oligosaccharide and lipid A from bacteria of
      genera Clavibacter, Ralstonia, Pseudomonas and Rhizobium, have been studied.
      Phenotypization of the studied strains has been carried out and chemotaxonomic
      criteria for creation of serological classification schemes have been proposed.
      Serogrouping of strains is determined by the availability and chemical nature of
      lateral substituents of the basic chain of O-specific polysaccharide.
      Interrelation between physico-chemical characteristics of the polysaccharide
      complex of rhizobia and formation of bean-rhizobial symbiotic structures has been
      shown. It is established that polysaccharides, lipo- and exopolysaccharides are
      efficient immunomodulators, manifest high antileucosis and antimetastasis
      activities. Physico-chemical properties, specificity, kinetics and action
      mechanism, structure of active and substrate-binding centres of bacterial and
      fungal enzymes: alpha-amylase, alpha-galactosidase, galactose oxidase. Data
      obtained permitted developing recommendations on enzymes application to some
      fields of the national economy.

PMID- 10077958
TI  - [The biology of bacteria that assimilate C1--C2 compounds and the biotechnology
      aspects of their use].
AB  - Main directions of the research work of the Department of Biology of Gas
      Oxidizing Microorganisms are described in the paper. Fundamental studies concern
      ecology, selection, taxonomy, physiology, biochemistry, genetics of bacteria
      utilizing C1--C2 compounds, mathematical simulation of microbiological processes.
      Applied studies are devoted to development of scientific basis of biotechnologies
      for synthesis of important products (single cell protein, exopolysaccharides,
      food ingredients, biogas) from non-food substrates, search for the hydrocarbon
      deposits and protection of the environment.

PMID- 10077959
TI  - [Transplantation of the vascular pedicled thoracicus longus nerve for recovering
      sensory capacities in the mentalis nerve supply region].
AB  - In the last few years microvascular techniques have improved the morphologic and
      functional results of reconstructive facial surgery. A main advantage is that
      neuronal rehabilitation can be achieved after tumor surgery. In this study the
      vascularized thoracic long nerve transplant was used for neuronal reconstruction
      of the alveolar inferior nerve after resection during tumor surgery. Five
      patients were examined for recurrence of neuronal function in the mental nerve
      and lip region after surgery in monthly control intervals. Sensation of pressure
      and pain was recorded for 3 months, sensation of contact and vibration feeling
      for 5 months and temperature sensation for 7 months after neuronal
      reconstruction. Nine months after surgery the mental nerve and lip sensitivity
      were the same on both sides--the reconstructed and the healthy side--in four
      patients. Thus, the vascularized thoracic long nerve seems to be a good nerve
      transplant for bridging defects of the alveolar inferior nerve after resection
      during tumor surgery.

PMID- 10077960
TI  - [Dental assisted distraction osteogenesis of the mandible. Results of an animal
      experimental study and initial clinical application].
AB  - In recent years lengthening of the human mandible by distraction osteogenesis has
      become an accepted treatment for correction of severe mandibular disto-basal
      discrepancies. Using extra-oral and intra-oral distraction devices the technique
      of osseous anchorage is usually preferred. To avoid the disadvantages of this
      method it is the aim of many research groups to develop a tooth-borne
      distraction. In the present animal study, six minipigs were treated with a new
      solely dentally fixed orthodontic device for mandibular distraction osteogenesis.
      Following bilateral osteotomy in the dentigerous area of the mandibular body and
      a latent period of 2-7 days, a mandibular lengthening of 9 mm was reached within
      a period of 9 days. This situation was retained using the distraction device for
      6 weeks. After the removal of the apparatus, there followed a period of another 6
      weeks of consolidation. The callus and bone formation and potential dental,
      periodontal and nerval reactions were radiologically examined and histological
      examination was performed at the end of the experiment. At 12 weeks after the
      mandibular lengthening, the osteogenesis in the distraction areas was complete.
      No destructive processes were recognizable, either at the roots or at the
      periodontium of the teeth near the osteotomy gap. The mandibular nerve at the
      osteotomy site remained intact. The results justified transferring this procedure
      to humans. The clinical application of the device is presented.

PMID- 10077961
TI  - [Changes in the nasal airway by transverse distraction of the maxilla].
AB  - OBJECTIVE: To investigate nasal airway changes through transverse maxillary
      distraction osteogenesis by means of an objective, reliable, noninvasive
      investigation technique with special attention to nasal valve changes and
      widening of the posterior maxilla. PATIENTS AND INTERVENTION: Eight patients with
      a severe maxillary transversal deficit underwent surgically assisted rapid
      palatal expansion in local or general anesthesia. Before and after the
      distraction process, a transnasal series of acoustic measurements of nasal airway
      profile was performed under topical decongestion. Nasal volume was calculated by
      integration of the area profile. The cross-sectional area of the nasal valve was
      also determined. RESULTS: A significant enlargement of nasal volume was recorded
      in all patients (P < 0.01: Wilcoxon signed rank test). The average increase
      measured 5 cm3 (23%). The increase in volume was recorded in all parts of the
      nasal cavity, indicating complete maxillary expansion even in the posterior
      segment. The nasal valve area raised from 0.56 to 0.70 cm2 (P < 0.01). Six out of
      eight patients reported striking improvement of nasal patency after maxillary
      distraction. CONCLUSION: Besides correction of the maxillary arch deformity,
      rapid palatal expansion contributes to improved nasal patency by resolving nasal
      valve constriction. Significant widening of the posterior nasal cavity was
      achieved, indicating a translational pattern of maxillary movement, although the
      pterygomaxillary junction was not touched in the osteotomy.

PMID- 10077962
TI  - [Time saving and effective method of temporary intraoperative reposition in
      mandibular fractures. Realization with the FAMI screw].
AB  - Open reduction and rigid fixation with maxillomandibular fixation at least
      intraoperatively is the method of choice for treatment of mandibular fractures.
      We report an effective method of internal temporary fixation which significantly
      facilitates fracture reduction and stabilization. The technique is used in
      combination with special FAMI screws and a monocortical miniplates system
      according to Champy, which eliminates in most cases the need for
      maxillomandibular fixation. Our results in 78 patients with mandibular fractures
      confirmed the reliability and the efficiency of the internal temporary fixation.

PMID- 10077963
TI  - [Low energy extracorporeal shockwave therapy (ESWT) for treatment of myogelosis
      of the masseter muscle].
AB  - Patients with functional disorders of the temporomandibular apparatus often show
      painful myogelosis, especially of the masseter muscle. The cause is hypertonia of
      the affected muscle. The aim of the presented single-blinded clinical trial was
      to analyze the effects of low-energy extracorporeal shock waves on patients with
      pain sensitivity in this region. Participating in the trial were 50 patients with
      painful, palpable and sonographically evident myogelosis of the masseter muscle.
      Half of the patients received a single application of 250 impulses of 0.04
      mJ/mm2. The second half received an equivalent placebo treatment with the shock
      wave impact being inhibited by a neopren insert. It was shown that in 64% of the
      patients significant alleviation of pain with palpable and sonographically
      evident softening of the myogelosis could be achieved. In 40% of the patients the
      therapeutic result could be conserved over a period of 2 weeks. The difference
      from the placebo group was statistically highly significant. ESWT is thus an easy
      to-use, non-invasive method of initial pain therapy for patients with functional
      disorders. To preserve the long-term therapeutic result, additional functional
      therapy is nevertheless necessary.

PMID- 10077964
TI  - [New aspects for indications of surgical management of intra-articular and high
      temporomandibular dislocation fractures].
AB  - Conservative treatment of TMJ condylar fractures (groups V and VI according to
      Spiessl and Schroll 1972) often shows poor clinical results. This follow-up study
      was designed to objectify the benefits of an operative procedure by electronic
      computer-assisted recording of condylar movements. Sixty-three individuals with a
      total of 77 condylar fractures (42 diacapitular fractures, 35 high condylar
      process fractures) underwent surgery over a preauricular approach. Osteosynthesis
      was performed according to the intraoperative site either by PDS pins, titanium
      lag screws, microplates, miniplates or a combination of these materials.
      Radiological controls showed a considerable loss of height of the condylar
      process in the diacapitular group of fractures affecting the lateral condylar
      pole (n = 20). Condylar deformations in these cases were similar to the high
      condylar process group, whereas diacapitular fractures not affecting the lateral
      condylar pole (n = 22) had better radiological results. Axiographic tracings of
      TMJ movements in all groups as well as clinical functional analysis demonstrated
      highly satisfactory functional results within physiological limits. Compared to
      data referring to individuals treated conservatively, far fewer irregularities of
      axiographic tracings were observed in this group. Limitations of condylar
      movements nevertheless were found frequently in the high condylar process group
      (35%). As a severe complication, permanent facial nerve palsies occurred in six
      individuls due to the preauricular approach employed. After a modification using
      a temporal extension, only one minor partial lesion occurred in 97 operations.

PMID- 10077965
TI  - [Increased occurrence of oral lichen planus in hepatitis C infection].
AB  - The present study evaluated the risk of hepatitis C virus-infected (HCV) patients
      in Germany to develop oral lichen planus (OLP). We screened 127 patients with
      chronic HCV-infection for OLP. In three of 127 patients (2.4%) OLP was found.
      Twenty-four patients with OLP were examined for hepatitis C. Only one patient
      (4.2%) was positive for HCV-RNA. Our data show no increased prevalence for OLP in
      German patients infected with HCV. Also no increased rate of HCV infection in OLP
      patients was found in this study. Further studies of HCV-infected patients from
      different geographical areas and ethnic groups are necessary to determine the
      rate of OLP in HCV-infection and to clarify whether HCV acts locally to develop
      OLP, or whether host immune response to HCV is of importance.

PMID- 10077966
TI  - [Regeneration of mouth mucosa in the buccal plane following graft procurement for
      reconstruction of bulbar urethral stenoses].
AB  - The use of free buccal mucosal grafts in the treatment of urethral strictures has
      become very popular. In 1996 and 1997 we harvested free buccal mucosal grafts up
      to 7 cm long and 4 cm wide from 12 patients who underwent urologic surgery for
      urethral strictures. In 2 patients the donor site was closed primarily by
      sutures. Four patients received Lyodura and another 4 patients received
      Syspurderm as temporary wound coverage. In 2 patients Ethisorp patches were used.
      Donor site pain was judged by the patients on a visual analogue scale during the
      first postoperative week. The 2 patients who received the Ethisorp patches
      complained of more intense pain, probably caused by the rigidity of the material.
      In all patients regeneration of the donor site mucosa was good. During the follow
      up period of 4-18 months scar formation at the lower vestibulum was noticed as
      the only complication. Permanent limitation of mouth opening, stenosis of the
      parotid duct or hypesthesia did not occur.

PMID- 10077967
TI  - [Components of antibacterial and fibrinolytic activity of human saliva in normal
      and disordered wound healing].
AB  - Following oral surgery, there are sometimes disturbances in wound healing. It was
      the aim of this investigation to look for relationships between the composition
      of saliva and disturbed wound healing. Resting as well as stimulated fasting
      whole saliva was collected from 96 patients (19 to 53 years of age) prior to oral
      surgery. Flow rate, pH, standard bicarbonate, total buffer bases, peroxidase,
      lysozyme, thiocyanate, secretory immunoglobulin A, lactoferrin, total protein,
      tissue type plasminogen activator, and plasminogen activator inhibitor were
      determined. The salivary data of eight patients who suffered from disturbed wound
      healing were compared to the data of 20 randomly selected patients with normal
      wound healing. Patients with disturbed wound healing revealed increased
      activities and secretion rates for peroxidase in resting saliva. In stimulated
      saliva, decreased secretion rates for thiocyanate and total protein were found.
      Not a single salivary factor was able to discriminate both groups of patients
      with sufficient accuracy, but with a combination of tissue type plasminogen
      activator, peroxidase, plus secretory immunoglobulin A measurements from resting
      whole saliva a clearly improved and acceptable discrimination of the two patient
      groups was possible. A discriminant function including six salivary factors could
      be used to completely separate both groups.

PMID- 10077968
TI  - [Therapy refractory idiopathic thrombocytopenia. Contraindication for dental
      surgery interventions].
AB  - Hemorrhagic diathesis represents a high risk for oral surgery. In clinical
      practice various kinds of diathetic diseases are seen that are of plasmatic,
      vascular, thrombocytic and hypertensive origin. Usually these patients will be
      primarily referred to the hospital as high-risk cases. Therefore, a broad
      spectrum of diagnostic and therapeutic interdisciplinary methods are available,
      so that as a rule it is possible to obtain a clear picture of the severity of the
      bleeding tendency. We represent a case of a 58-year-old woman who had decayed
      teeth with chronic periodontal and periapical lesions, who could not be treated
      by oral surgery because of refractory idiopathic thrombocytopenic purpura (ITP)
      with 1000 platelets/microliters. The patient's history showed that various
      hematologic concepts had been tried, including splenectomy, but all had failed
      entirely. After therapy with steroids, immunosuppressive and cytostatic agents,
      and even after administering immunoglobulins and substitution with platelets, the
      count did not increase; thus, an absolute contraindication for all kinds of
      surgery was declared. This rare example indicates that unmanagable bleeding
      diseases still exist that should be known by dentists and oral surgeons to
      prevent making deleterious therapeutic decisions.

PMID- 10077969
TI  - [Amyloidosis of the tongue as a possible diagnostic manifestation of
      plasmacytoma].
AB  - Plasmocytic non-Hodgkin's lymphoma is the most common tumor of bone and bone
      marrow, typically diagnosed by symptoms such as monoclonal paraproteinemia,
      proteinuria, anemia and hypercalcemia. In its progress, deposits of amyloids in
      almost all organs can be observed. However, plasmacytomas which are diagnosed by
      macroglossia of primarily unknown etiology are rare. This case report presents a
      61-year-old woman who suffered from a persistent swelling of the tongue with
      painful ulcerations. A biopsy led to the diagnosis of primary systemic
      amyloidosis of the light-chain type, which subsequently proved to be a
      plasmacytoma with lambda light-chains stage II after Durie and Salmon. In the
      course of the disease the patient developed further deposits of amyloids in the
      whole gastro-enteric system. Macroglossia as a primary manifestation of
      plasmacytoma is rarely described in medical literature. However, reports on
      deposits of amyloid in the tongue in advanced stages of disease are well known.

PMID- 10077971
TI  - [Past and present studies on ABO blood group system].
AB  - The author engaged himself in the studies of ABO blood group system for the last
      three decades, and reviewed the progresses in this period, which were classified
      into following 5 items. 1. H-, A- and B-active oligosaccharides were isolated
      from the globoside fractions from human erythrocytes by ozonolysis. One of the H
      active oligosaccharide with short carbohydrate chain is a pentasaccharide:
      Fuc(alpha 1-->2)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc, and the
      other with long carbohydrate chain is a heptasaccharide: Fuc(alpha 1-->2)Gal(beta
      1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc. Hexa
      or octasaccharides with blood group A- or B-activity have an additional alpha-N
      acetylgalactosaminyl residue or alpha-galactosyl residue, which joints with alpha
      1-->3 linkage to subterminal beta-galactose of the both of H-active
      oligosaccharides, respectively. 2. A blood group A-gene specified alpha-N-acetyl
      galactosaminyltransferase (A-enzyme) catalyzes the transfer of N
      acetylgalactosamine from the UDP-sugar to the subterminal beta-galactosyl residue
      of blood group H-active carbohydrate chain, and a blood group B-gene specified
      alpha-galactosyltransferase (B-enzyme) catalyzes the transfer of galactose from
      the UDP-sugar to the subterminal beta-galactosyl residue of blood group H-active
      carbohydrate chain, respectively. Either the A- or B-enzyme can not transfer the
      substrate sugar to the carbohydrate chain lacking alpha-fucosyl residue of H
      determinant, and it is the reason why the synthesis of blood group A- or B
      antigenic structure in inhibited in the tissues of Bombay phenotype and in the
      secretory glands of the nonsecretor. 3. Specific antibody either to the A- or B
      enzyme can be introduced in the serum of the rabbit which was immunized with the
      A- or B-enzyme preparation, respectively. And immunological cross reaction is
      also present between the A- and B-enzyme, but the immunologically cross reactive
      material can not be found in the blood group O individual. The absence of
      immunologically cross reactive material in the blood group O individual is
      supported by a fact that the cross reactive antibody similar to the antibody in
      rabbit serum was present in the serum of the chronic myeloid leukemia patient,
      who was belonged to blood group B and treated with blood group incompatible bone
      marrow transplantation from blood group O donor, because it is acceptable to
      speculate that the grafted lymphocytes react to the B-enzyme in the recipient and
      produce the anti-enzyme antibody. 4. The immunological profiles described above
      are compatible with the cDNA structures of human blood group ABO alleles
      presented by Yamamoto F. et al. Their gene model is that the cDNAs of blood group
      ABO alleles are highly homologous, but the cDNA of common O allele is non
      functional due to a single nucleotide deletion close to the 5'end of the coding
      sequence, which causes a frame shift of the codon, and results in truncated
      peptide. 5. Transcription of the human blood group ABO gene can be enhanced by a
      CBF/NF-Y which binds the minisatellite on the 5'-upstream sequence of the gene.

PMID- 10077972
TI  - [Practice and research of forensic medicine learned from the dead].
AB  - Practice and Research of Forensic Medicine Learned from the Dead' is presented by
      looking back my 29 years' carrier as a forensic pathologist. After joining in
      Department of Forensic Medicine, Kumamoto University in 1969, I had spent several
      happy years with studying on postmortem corneal clouding. Soon I began to have
      doubts on a purpose of forensic autopsy in my department then, which seemed to be
      only to/under the police. I spent one year at Department of Forensic Medicine,
      Leeds University in England in 1979-1980 and experienced Forensic Medicine not
      only for the police but also for the society in general. Visiting several
      university departments in Europa at that time, I felt confident that Forensic
      Medicine is one special field of medical sciences and will be worth a subject to
      devote my life. Clinical Forensic Medicine is one field of forensic medicine. Its
      importance has been recognized in the society by increasing numbers of felonious
      crimes and campaigns of human rights throughout the world. In 1996, the 4th
      International Conference of World Police Medical Officers in Clinical Forensic
      Medicine was ended in a great success in Kumamoto, Japan. Now evaluation and
      development of Clinical Forensic Medicine are very essential for both forensic
      pathologists and clinicians to serve for the society. My own activities of
      teaching traffic safety and preventing child abuse and neglect were cited as
      examples of 'Practice of Forensic Medicine Learned from the Dead'. Studies on
      differentiation of postmortem discoloration and antemortem bleeding by
      glycophorin A or erythrocyte membranes and an international joint research
      project with Tanzania on neuropathology of AIDS were examples of 'Research of
      Forensic Medicine Learned from the Dead'. It is an important mission for a
      forensic pathologist to work for/with the police to solve crimes by hearing a
      voice of the dead on an autopsy table. Through friendship with foreign
      colleagues, however, I have learned much about what should be a forensic
      pathologist and have been inspired with a phrase, 'The information learned from
      studying the dead could be used to help the living.' by Dr. T.A. Gonzales of the
      Chief Medical Examiner's Office of New York. Because social activities of
      preventing crimes and accidents are very much important matters indeed, every
      forensic pathologist must devote his/her forensic practice and research to
      achieve a peaceful end of life for every citizen, I believe.

PMID- 10077973
TI  - [Epidemiological study of suicide in Japan--is it possible to reduce committing
      suicide?].
AB  - It is reported that the annual number of suicides in Japan is more than 20,000,
      which is as twice as the number of death by traffic accidents. Nevertheless, few
      protective activities have been developed by government or society. This paper
      introduces the actual states of suicide in the past few years in Japan, expecting
      to start a movement for reducing suicidal number by government, society and
      family in Japan. The number of suicide was less than 15,000 in the late 1960s,
      but it increased to more than 20,000 in 1970s, which has not been reduced up to
      the present and the highest number 256,000 was recorded in 1986. The Ministry of
      Welfare reports that the prefectures showing higher rate of suicide have been
      Akita, Iwate and Niigata, whose suicide rates are 10 points higher than that of
      the national average. On the other hand, the prefectures such as Nara, Shiga,
      Shizuoka and Kanagawa have shown lower rate of suicide. In all the prefectures,
      the number of males is constantly much larger than that of females and,
      furthermore, the rate of suicide in the male and female aged group (over 65 years
      old) is much higher than that of the under-64-year-old group. As a background of
      suicide, psychiatric disorders account for 30-50% of all suicides in the younger
      and prime generations, but as a motive of suicide the pain of sickness amounts to
      60-70% in the aged group. It is suspected by our epidemiological investigations
      that the pain of sickness is not a true motive for committing suicide. Sickness
      usually accompanies anxiety, pessimistic view of life, loss of an important part
      in his/her family and economical uneasiness. The most frequently used method for
      committing suicide in male and female especially in the aged group is hanging,
      and next to this are inhalation of car exhaust, drowning oneself and taking
      poisons. Firearms are quite rarely used in Japan. Aging, mental disorders and
      genetic factors are considered to be risk factors for suicide attempt. It should
      be pointed out that betterment of home life, mental independence, death education
      and forced intervention by psychiatrists are required to reduce the number of
      suicides.

PMID- 10077974
TI  - [High activity of deoxyribonuclease I identified in human pituitary gland-
      structure and function].
AB  - Human deoxyribonuclease I (DNase I) showing genetic polymorphism has been
      evaluated to be well suited for practical purposes such as criminal
      individualization or paternity testing. DNase I has so far been recognized to be
      functionally active only during the digestion of exogenous DNA, because this
      enzyme is secreted into the alimentary tract from exocrine glands such as the
      pancreas. However, it was discovered that the human pituitary gland, non
      digestive tissue, exhibited higher DNase I enzyme activity and expression of its
      gene, being comparable to those of the pancreas. These findings strongly support
      the hypothesis that DNase I plays (a) biological role(s) other than a digestive
      one. Furthermore, we observed that all hypothalamic hormones examined induced a
      significant elevation or decline of pituitary, serum and urine DNase I activity
      in a rapid and transient manner similar to the corresponding anterior pituitary
      hormones. Therefore, DNase I was demonstrated to be coupled with the secretion of
      anterior pituitary hormones in a hypothalamic pituitary system. Thus, recent
      progress of our studies on human DNase I for purpose of practical uses in
      forensic sciences has permitted us to succeed in the clarification of a novel
      biological function inherent in the enzyme.

PMID- 10077975
TI  - [Metabolic activation of azaheterocyclics induced dopaminergic toxicity: possible
      candidate neurotoxins underlying idiopathic Parkinson's disease].
AB  - In 1983, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a contaminant of
      "synthetic heroin", has been reported to induce parkinsonian symptoms in humans,
      who were responsive to L-DOPA therapy, as a result of the degeneration of
      nigrostriatal neurons. The "MPTP story" hypothesizes that Parkinson's disease may
      be initiated or percipitated by environmental and/or endogenous toxins by a
      mechanism similar to that of MPTP in genetically-predisposed individuals. Several
      classes of heterocyclic molecules structurally related to MPTP have been advanced
      as possible neurotoxicant precursors underlying the nigrostriatal degeneration in
      Parkinson's disease. Indoleamine-related beta-carbolines (beta Cs), a class of
      heterocyclics which are basically plant alkaloids, are proposed as the most
      promising natural MPTP-like toxicants or protoxicants. In this article, beta Cs
      and N-methylated beta C cations are reviewed with regards to their formation,
      bioactivation, toxicity and presence in the human central nervous system. The
      enzymes in mammalian brain particulate fractions methylate beta Cs, sequentially
      forming 2-mono-[N]-methylated (2-Me beta C+s) and neurotoxic 2,9-di-[N, N']
      methylated (2,9-Me2 beta C+s) beta-carbolinium cations. These beta C+s are
      structural analogs of 1-methyl-4-phenylpyridinium ion (MPP+), an active
      metabolite of MPTP, with a nitrogen bridge. The beta C+s not only inhibit DA
      reuptake and tyrosine hydroxylase, but also function as NADH-linked respiratory
      inhibitors in isolated mitochondria. The quarternization of beta C strikingly
      increased the affinity for dopamine transporter with 2-10 times greater Km and 10
      times smaller Vmax values than MPP+. Furthermore, we have found higher
      concentrations of beta C+s localized in the nigra than in the cortex, and
      observed the S-adenosyl-L-methionine-dependent methylation of 2[beta]- and
      9[indole]-nitrogens of beta Cs in non-parkinsonian human brains. Moreover, the
      cerebrospinal fluid levels of these beta C+s are higher in parkinsonian than non
      parkinsonian patients. Simple beta-carboline induced parkinsonian-like symptoms
      in mice via N-methylation. These results indicated that beta C is a selective
      dopaminergic toxin precursor, that is sequentially methylated to form 2,9-Me2
      beta C+ that could be an underlying factor in idiopathic Parkinson's disease.

PMID- 10077976
TI  - [Lipid peroxidation induced by hemoproteins in terms of forensic medicine].

PMID- 10077977
TI  - [Medicolegal aspects and molecular pathology of ischemic heart disease].

PMID- 10077978
TI  - Sudden natural death in driving: case studies in the western area of Kanagawa.
AB  - To assess their incidence and implications, we made a retrospective study of
      sudden unexpected natural deaths during driving that occurred in the five year
      period between 1992 and 1997. During that period, 188 postmortem examinations
      were performed on driver victims of traffic accidents. Of these, 15 (8%) were
      found to have died of natural causes such as heart disease or cerebral
      hemorrhage. Marked findings in this study were that no persons over 70 years of
      age and more occupational drivers suffered natural death. Although no passengers
      or pedestrians were injured, as many as eight vehicles collided with another
      object or vehicle. Sudden natural death, particularly from cerebral hemorrhage,
      of drivers might be hazardous to other road users.

PMID- 10077979
TI  - [Studies on properties of cross-reacting anti-A,B antibodies in group O sera].
AB  - It is widely accepted that the sera of group O individuals contain three
      antibodies: anti-A, anti-B, and an antibody capable of reacting with both A and B
      red cells, generally called anti-A,B. The exact nature of the anti-A,B antibody,
      however, has been controversial for a long time. This paper attempts to answer
      the question of the anti-A,B antibody. The anti-A,B antibody was separated and
      purified from pooled group O sera by six consecutive runs of affinity
      chromatography on alternating columns of group A-specific and group B-specific
      immunoadsorbents. The final eluate, the anti-A,B preparation, was found to be
      homogeneous in the polyacrylamide gel disc electrophoresis and
      immunoelectrophoresis. Immunodiffusion studies, together with treatment with 2
      mercaptoethanol, showed the anti-A,B antibody to be IgG. The anti-A activity of
      the anti-A, B antibody was inhibited with group A secretor saliva and group A
      specific substances, but not with group B secretor saliva and group B-specific
      substances, and the anti-B activity of the antibody was inhibited with group B
      secretor saliva and group B-specific substances, but not with group A secretor
      saliva and group A-specific substances. Then, Fab fragments of the anti-A,B
      antibody were prepared by papain digestion. Indirect hemagglutination tests for
      the Fab fragments by use of an anti-Fab antiserum demonstrated that the Fab
      fragments possess both of anti-A and anti-B activity. Then, rosetting tests for
      the anti-A,B antibody were carried out using A- and B-specific trisaccharides
      covalently attached to silica particles. The results showed that the anti-A,B
      antibody linked A- and B-specific trisaccharides to A and B red cells. These
      results strongly indicate that the anti-A,B antibody is an antibody with
      significant affinity for both group A and group B antigens rather than an
      antibody directed against a structure common to group A and group B antigens. The
      conclusions based on the above experiments are that the anti-A,B antibody in
      group O sera is IgG and presumably possesses dual specificity regarding to anti-A
      and anti-B activity.

PMID- 10077980
TI  - [Hemorrhagic shock death caused by not so severe injury during the medication of
      anticoagulants].
AB  - A 73-year-old man receiving anticoagulants (warfarin potassium) orally with a
      history of prosthetic heart valve replacement was struck by a truck. When
      admitting to the hospital, he complained of lumbago with laboratory findings of
      anemia and prolongation of prothrombin times. Twenty-two hours after the
      accident, he died suddenly in the hospital and forensic autopsy was performed 9
      hours after his death. Autopsy findings revealed marked subcutaneous and
      intramuscular hematoma in the lumbar and gluteal region and anemic change of
      viscera. Furthermore, 854 ng/ml of warfarin which was well accordance with the
      therapeutic levels was detected in the serum obtained from cadaver by using gas
      chromatography-mass spectrometry. Therefore, we concluded that the man had died
      of hemorrhagic shock caused by the force acting to the lumbar region accompanied
      by the influence of anticoagulant action of warfarin. To our knowledge, this is
      the first report to detect the warfarin from cadaver's serum. In dealing with the
      unnatural death of the patient receiving the anticoagulants, it is valuable to
      survey the medications and detect the presence of anticoagulants in cadaver.

PMID- 10077981
TI  - [Effects of hemodialysis membrane on serum lipid profile of maintenance
      hemodialysis patients].
AB  - Atherosclerosis and lipid abnormalities are still insuperable complications for
      maintenance hemodialysis patients. We observed the serum lipid profile of 27
      maintenance hemodialysis patients (M : F; 20 : 7, age; 54.9 +/- 6.2 y. o.,
      hemodialysis duration; 10.8 +/- 4.9 years, body weight; 53.6 +/- 4.4 kg) using a
      low flux cellulose membrane, cellulose (1.5 m2), a vitamin-E-modified dialysis
      membrane, CL-15E (CL- 15E 1.5 m2, Terumo), and polysulfon, PS (PS-1.3UW 1.3 m2,
      Fresenius) dialysers. Each membrane dialyzer was used for 3 months. The blood
      flow rate was 200 ml/min, and hemodialysis time, 4 hours. When the dialyzers were
      replaced, fasting blood was collected at the beginning of hemodialysis and serum
      lipid parameters were measured. Seven additional maintenance hemodialysis
      patients were selected and TC, TG, HDL-C were measured as controls, because their
      dialyzers (low flux cellulose 1.5 m2) and hemodialysis conditions were not
      changed during the study. TC was decreased by PS and there were significant
      differences between cellulose and PS, and between CL-15E and PS. However, these
      changes were conducted within the normal range of TC. TG was not significantly
      changed during the study. HDL-C was decreased by CL-15E and PS as well as TC.
      There were significant differences in HDL-C between cellulose and CL-15E, and
      between cellulose and PS. Apo B, Apo B/A-I were decreased by PS and there were
      significant differences between cellulose and PS, respectively, LP(a) was not
      changed during the study. RLP-C (Cellulose vs. PS, CL-15E vs. PS), VLDL-C
      (Cellulose vs PS), and LDL-C (cellulose vs. PS, CL-15E vs. PS) were significantly
      decreased between membranes, respectively. Although the precise mechanism is yet
      unknown, the uptake of LDL and remnant into receptors of the liver might be
      improved by PS hemodialysis. In conclusion, these data suggest that PS decreased
      the serum levels of the lipid profile in maintenance hemodialysis patients and
      may be effective in improving their lipid abnormality.

PMID- 10077982
TI  - [A study of association between lean body mass and serum insulin-like growth
      factor-1 in continuous ambulatory peritoneal dialysis patients].
AB  - Malnutrition is one of the major issues associated with high mortality and
      morbidity in chronic dialysis patients. Several methods to evaluate the
      nutritional status of these patients have been attempted for example
      anthropometric measurement and biochemical parameters. Recently, it was reported
      that insulin-like growth factor-1 (IGF-1) has been valuable for estimating
      nutritional status. In this study, we measured lean body mass (LBM) by dual
      energy X-ray absorptiometry (DXA), IGF-1 and other biochemical parameters in 35
      patients on CAPD. Two years later, the second measurement of LBM was performed,
      and we assessed the percent changes of LBM and biochemical parameters. There was
      negative correlation between the percent changes of LBM and the duration of CAPD.
      In patients treated with CAPD for less than 36 months (group I) LBM increased,
      however, it decreased significantly in those treated for more than 36 months
      (group II). On the other hand, in group I there was a positive correlation
      between the percent changes of LBM and IGF-1. In group II there was no
      correlation between the percent changes of LBM and any other biochemical
      parameters. It could be concluded that IGF-1 is one of the predisposing factors
      for improving LBM of patients on CAPD for a limited duration.

PMID- 10077983
TI  - [Usefulness of magnetic resonance imaging of the wrist for the early diagnosis of
      dialysis-related amyloidosis].
AB  - Dialysis-related amyloidosis (DRA) is a major complication of long-term
      hemodialysis patients. The onset of arthropathy is frequently preceded by carpal
      tunnel syndrome, but the early non-invasive diagnosis of DRA remains unclear.
      beta 2-microglobulin amyloid deposits in joint synovia and soft tissue precede
      radiological abnormalities. Magnetic resonance imaging (MRI) may play a more
      important role in the early diagnosis of DRA, because it allows direct
      visualization of synovitis and deposition of abnormal soft tissue. The purpose of
      this study was to evaluate the usefulness of MRI of the wrist for the early
      diagnosis of DRA. The study included 72 patients (male 37, female 35) undergoing
      hemodialysis from initiation to 20 years. The patients were examined by MR images
      of synovitis, deposition of abnormal soft tissue and cystic bone lesions at the
      wrists. Normal MR images of synovia and soft tissue were defined in 6 control
      subjects (2 normal 4 non-dialysis patients). Synovitis of the carpal bones was
      found in 23% of the patients at the start of hemodialysis. Deposition of abnormal
      soft tissue in the carpal canal and cystic bone lesions were detected after 1 and
      2 years of hemodialysis, respectively. All findings were increased significantly
      with an increasing duration of dialysis. Synovitis was present in 90% of the
      patients with deposition of abnormal soft tissue, and in 80% of the patients with
      cystic bone lesions. beta 2-microglobulin value was significantly higher in
      patients with synovitis, deposition of abnormal soft tissue and cystic bone
      lesions than in patients without these findings. Our experience suggest that
      synovitis examined by MRI of the wrists is useful for the early diagnosis of DRA.
      Thereby, intensive follow-up and management of DRA are required in patients with
      synovitis at the start of hemodialysis.

PMID- 10077984
TI  - [Effects of deoxyspergualin on proliferative glomerulonephritis].
AB  - A clinical trial of the immunosuppressive drug, deoxyspergualin (DSG), was
      conducted in five patients with various forms of proliferative glomerulonephritis
      (GN), such as IgA nephropathy in 2 patients, purpura nephritis in 1,
      membranoproliferative GN(MPGN) in 1, and rapidly progressive GN (RPGN) in 1
      patient, respectively. DSG was intravenously administered at a daily dose of 0.25
      or 0.5 mg/kg for 4 weeks. A marked decrease in proteinuria (to less than 50% of
      baseline) was observed in four patients. The other patient showed 38% reduction
      of proteinuria. However, proteinuria exacerbated again after discontinuation of
      DSG in three patients during a four-week follow-up period. Marked decrease
      (3,000/microliter) in white blood cell (WBC) counts was observed in three
      patients during the course of DSG treatment. We concluded that DSG therapy is
      beneficial in reducing proteinuria in patients with various forms of
      proliferative GN. However, since proteinuria increased after the discontinuation
      of DSG and serious leukocytopenia was observed, indiscriminate use of DSG in
      proliferative GN should be discouraged.

PMID- 10077985
TI  - [Successful treatment of acute renal failure in a patient with essential mixed
      cryoglobulinemia using prednisolone and cryofiltration].
AB  - We report a case of acute renal failure associated with cryoglobulinemic
      glomerulonephritis. The patient, a 49-year-old woman, was referred to our
      hospital because of acute nephritic syndrome. After admission, she developed
      oliguria, and hemodialysis was instituted. Renal biopsy was performed and the
      specimens showed moderate endocapillary proliferation, large deposits filling the
      capillary lumen ("intraluminal thrombi"), and a double-contoured appearance,
      which are typical morphologic features of cryoglobulinemic glomerulonephritis.
      Immunoelectrophoresis showed a monoclonal increase of IgM kappa. On the basis of
      these findings, we diagnosed type II essential mixed cryoglobulinemia.
      Cryofiltration was performed with oral administration of prednisolone. Following
      the start of therapy, the patient's renal function gradually improved. Because of
      severe hypoproteinemia, cryofiltration was discontinued after three sessions.
      However, renal function recovered and was maintained with prednisolone only. This
      case shows that acute oliguric renal failure caused by cryoglobulinemic
      glomerulonephritis can be reversible if immunosuppressive therapy, together with
      plasmapheresis in more severe cases, is instituted promptly.

PMID- 10077986
TI  - [Study of association between lean body mass and serum insulin-like growth factor
      1 in continuous ambulatory peritoneal dialysis patients].

PMID- 10077987
TI  - [Recent conception of collagen diseases].
AB  - Collagen diseases or connective tissue diseases are defined as their pathological
      features. They are also regarded as rheumatic disorders in the sense of clinical
      classification and as autoimmune diseases in terms of the pathogenesis. In
      addition of the original big 6(SLE, RA, PSS, PN, PM/DM and RF), several disorders
      have been categorized in this entity. Although remarkable progress has occurred
      in understanding the mechanisms of several connective tissue diseases, therapy
      has lagged. Nevertheless, based on these findings, increasing knowledge on new
      therapeutic principles has been developed. Novel pharmacological and biological
      agents would act more specifically on interfering with ongoing immune processes.

PMID- 10077988
TI  - [Regulation of B cell differentiation].

PMID- 10077989
TI  - [The molecular mechanisms governing T cell development in the thymus].
AB  - Intracellular signaling events required for T cell development in the thymus have
      been investigated using various gene deficient and transgenic mice. Here, we
      summarize and discuss the recent results. Immature thymocytes immigrated from
      bone marrow are found to be committed to lymphoid lineage. First, the lymphoid
      progenitor proliferates in IL-7-dependent manner, and differentiates into the
      cells expressing preTCR complex. The expression of preTCR is required for
      differentiation to CD4+ CD8+ cells. Then, CD4+ CD8+ cells express TCR alpha beta
      and are subjected to positive and negative selection. Essential molecules for
      these selection events and gene activation required for lineage commitment to CD4
      or CD8 T cells are getting clear. In the near future, molecular mechanisms
      governing each developmental step of T cells will be clarified.

PMID- 10077990
TI  - [T cell receptor and its related molecules in signal transduction].
AB  - Engagement of the T cell receptor (TCR) by peptide antigen bound to the major
      histocompatibility complex molecules initiates a biochemical cascade involving
      protein tyrosine kinases (PTKs) such as Lck, ZAP70 and Csk, and protein tyrosine
      phosphatases (PTPases) such as CD45, SHP-1 and SHP-2. In the process of T cell
      activation, immune tyrosine-based activation motifs (ITAMs) and immune tyrosine
      based inhibitory motifs(ITIMs) within the cytoplasmic region of CD3 and CD152
      molecules play a key role in the activation of PTKs and PTPases. Consequently,
      Ras/MAP kinase and PLC gamma 1 pathways are activated to induce IL-2 gene
      transcription through AP-1 and NF-AT generation. Recent biochemical and genetic
      evidence has suggested that dysfunction in these TCR-related molecules resulted
      in immuno-deficiency, breakdown of tolerance and abnormal T cell development.

PMID- 10077991
TI  - [Chemokines and Chemokine receptors in collagen diseases].
AB  - The chemokine is a new class of cytokine. Now, more than 30 members of chemokine
      superfamily and 15 members of chemokine receptors (CXCR1-4, CCR1-8, CX3CR, CCR)
      have been identified. They were shown to be involved in the inflammatory
      response. The chemokine is classified into four subgroups (CXC, CC, C and CX3C).
      The local production of IL-8, MCP-1 and RANTES in rheumatoid inflamed joints has
      been reported. The predominance of several chemokines in other collagen diseases,
      such as SLE, systemic sclerosis and myositis is also described. Therefore, the
      inhibition of chemokines or chemokine receptors might be novel targets for
      various human disease, including collagen diseases.

PMID- 10077992
TI  - [Role of adhesion molecules in the pathogenesis of collagen diseases].
AB  - Adhesion molecules play important roles and involve in many aspects of cell-cell
      or cell-extracellular matrix interactions in collagen diseases. In the present
      article, we describe the role of adhesion molecules in the pathogenesis of
      collagen diseases. Adhesion molecules on endothelial cells participate in
      leukocyte recruitment in collagen diseases. Adhesion molecules on RA synoviocytes
      which interact with MNCs and destroy chondrocytes by pannus formation. In PSS,
      adhesion molecules on fibroblasts play important roles to form fibrosis by
      interacting with MNCs or collagen fibrils. We further mention on adhesion
      molecules in interaction between MNCs and muscle fibers in myositis, those in
      vasculitis in SLE and other diseases, and autoantibodies inducing adhesion
      molecules on endothelial cells in PSS and Wegener's granulomatosis.

PMID- 10077993
TI  - [Activation mechanism of the complement system].
AB  - Complement is an activation system designed for the elimination of pathogens and
      is activated in three ways, i.e. the classical, alternative and newly discovered
      lectin pathways. The classical pathway is initiated by the binding of C1 to
      immune complexes, whereas the alternative pathway is activated by pathogens
      themselves without involvement of immune complexes. Upon binding of MBL (mannose
      binding lectin) to certain carbohydrates on pathogens, the lectin pathway is
      activated by two C1r/C1s-like serine proteases termed MASP-1 and MASP-2, which
      are associated with MBL. As a result, C4, C2 and C3 are activated. The lectin
      pathway plays a crucial role in innate immunity both in vertebrates and in
      invertebrates. The mechanism underlying lectin pathway activation remains
      unsolved. From an evolutional point of view, the classical and lectin pathways
      are closely related.

PMID- 10077994
TI  - [Pathophysiology of inflammation and mechanisms of action of anti-inflammatory
      agents].
AB  - In this review, various targets for anti-inflammatory agents, and recent advances
      in mechanisms of action of glucocorticoids and nonsteroidal anti-inflammatory
      drugs are summarized.

PMID- 10077995
TI  - [Regulatory mechanisms of NK cell functions].
AB  - Natural Killer (NK) cells discriminate self from non-self in a manner distinct
      from T cells. NK cells exhibit cytotoxicity against "missing-self" by killing any
      cells in principle except normal self-cells. Cells expressing low levels of self
      MHC class I molecules such as tumor cells and foreign cells are killed, whereas
      normal self cells are neglected by NK cells. Although identities of activation
      receptors triggering NK activity are still unclear, recent studies have revealed
      molecules inhibiting cytotoxicity against normal self cells. In this review, we
      summarize current understanding of molecular basis for missing-self hypothesis
      and control mechanisms of NK cell activation.

PMID- 10077996
TI  - [Retroviruses and autoimmune diseases].
AB  - Various genetic factors and environmental factors are intricately intertwined in
      the pathomechanism of autoimmune diseases. Retroviruses, represented by HTLV-I
      and HIV, are known to relate to autoimmune disorders. However, the pathogenetic
      role of retrovirus and the relationship between retrovirus and autoimmune
      diseases are not clear. We found autoimmune diseases, such as arthritis,
      myositis, arteritis, dermatitis and T cell abnormality in HTLV-I transgenic rats,
      and studied the pathomechanism of the diseases by cell transfer experiments. Here
      we describe the relationship between retrovirus and autoimmune diseases and
      suggest that retrovirus plays a important role in the autoimmune diseases.

PMID- 10077997
TI  - [Autoantibodies and analysis of target antigens].
AB  - Autoantibodies in sera from patients with connective tissue diseases mainly
      target ribonucleoproteins (RNA-protein complexes) that are involved in important
      cellular functions such as gene transcription, RNA processing and protein
      translation. These autoantibodies are closely associated with specific diseases
      and clinical features, and are useful markers for diagnosis, classification of
      disease subsets, speculation of prognosis and disease activity. These target
      ribonucleoprotein antigens can be detected and characterized by sensitive RNA
      immunoprecipitation technique.

PMID- 10077998
TI  - [Analysis of susceptibility genes to rheumatic diseases].
AB  - Recent evidence suggests that most of the rheumatic diseases are complex or
      multifactorial diseases with contributions from HLA and multiple non-HLA genes.
      Studies using candidate gene approach suggested that early components of the
      complement pathway, Fc receptor IIa, IIIa, mannose-binding lectin, IL-10 and
      TNFR2 might be potential non-HLA susceptibility genes to systemic lupus
      erythematosus, although substantial difference among populations are reported.
      Linkage analyses using affected sib pairs indicated several candidate regions on
      chromosome 1. A recently completed genome-wide linkage analysis of rheumatoid
      arthritis revealed a number of possible candidate regions in addition to HLA.
      Identification of the susceptibility genes will be accelerated along with
      technological advances and the accomplishment of human genome project, and will
      deepen our understanding of rheumatic diseases.

PMID- 10077999
TI  - [Advances in systemic lupus erythematosus].
AB  - To help to understand recent progresses in studies on systemic lupus
      erythematosus (SLE), the essence of the Fifth International Conference on SLE
      that was successfully held at Cancun, Mexico on April, 1998 is reviewed. Among
      more than 400 papers, most highlighted topics were (1) relationship between
      hyperprolactinemia and SLE, (2) molecular mechanisms of antiphospholipid
      syndrome, (3) roles of anti-endothelial cell antibodies, (4) apoptosis in
      pathogenesis, (5) autoimmunity against nucleosomes, (6) penetration of
      autoantibodies into living cells, and so on. Clinical studies on adverse effects
      of current therapies, pioneer cases of autologous stem cell transplantation for
      refractory SLE, and other numerous cases that were full of suggestiveness were
      also reported by physicians from many countries.

PMID- 10078000
TI  - [The most recent advance in clinical investigation of rheumatoid arthritis].
AB  - The pathogenesis of rheumatoid arthritis (RA) can be explained through two main
      hypotheses: T cell-dependent and T cell-independent pathways. The mesenchymal
      hypothesis has proposed that after an initiation event triggered by T cells,
      synovitis is maintained by a proinflammatory cytokine cascade, chiefly a TNF
      alpha dependent cytokine cascade involving macrophages and synovial fibroblasts.
      T cells rather may not be important in perpetuating disease at the chronic
      stages. The T cell hypothesis has proposed that T cells are continuously involved
      in the pathogenesis of RA from its initiation phase through to the chronic
      stages. At the latter stages, T cells are importantly concerned in the cytokine
      network in rheumatoid joints. This paper reviews recent work in this area, and
      suggests that synergistic approaches targeting the two key aspect of the
      pathogenesis, T cells and the TNF-dependent cytokine cascade may be the best
      approach toward attempting a cure of RA.

PMID- 10078001
TI  - [Polymyositis and dermatomyositis].
AB  - This review summarizes the current progress in the clinical research on
      pathogenesis, diagnosis and treatment of polymyositis (PM) and dermatomyositis
      (DM). Recent studies on immunohistochemical and molecular findings of biopsied
      muscle tissues have shed light on pathogenetic mechanisms in myositis. Muscle
      imaging techniques such as ultrasonography and magnetic resonance imaging
      facilitate the assessment of the type (edema, inflammation, fat, and fibrosis),
      degree, and localization of these alterations. They are useful for the diagnostic
      evaluation and the assessment of treatment. Measurement of myositis-specific
      autoantibodies such as antisynthetases (anti-Jo-1 and others), anti-Mi-2, and
      anti-SRP is also useful for both diagnosis and classification of subgroup of
      patients with clinical, prognostic, and possible therapeutic implications. Novel
      treatment of refractory myositis includes methotrexate, cyclosporin, and
      intravenous high dose immunoglobulin. Anti-cytokine therapy will be a novel
      strategy for the treatment of myositis.

PMID- 10078002
TI  - [Systemic sclerosis: different subsets and disease remitting drugs].
AB  - Systemic sclerosis(scleroderma) is a generalized disorder of connective tissue
      characterized clinically by thickening and fibrosis of the skin and distinctive
      forms of involvement of internal organs notably the heart, lungs, kidneys and the
      gastrointestinal tract. Systemic sclerosis is a complicated disease with wide
      variation of manifestations and outcomes. It ranged from a disease which is
      extremely mild hardly effecting someone's life to one that is very severe causing
      an early demise. We describe different subsets of this complicated disease which
      allows physicians to have better understanding of its prognosis and outcome.
      Serum autoantibodies are useful in predicting prognosis, since they have
      association with serious visceral disease. Recently, laboratory studies are
      helpful both in identifying organ system abnormalities and the scleroderma
      specific autoantibodies. These autoantibodies are potentially very important in
      identifying subsets of patients. Using physical and serologic findings, the
      physician can determine the specific problems which are need to be addressed and
      treated.

PMID- 10078003
TI  - [Polyarteritis nodosa].
AB  - Polyarteritis nodosa (PAN) is the systemic necrotizing vasculitis on small and
      median muscular vessels. Recent studies reveal that PAN consists of classical PAN
      and microscopic polyangitis (MPA). MPO-ANCA, which is one of anti-neutrophil
      cytoplasmic antibody (ANCA), is involved in the pathogenesis of MPA. In future,
      by the progress of research of ANCA, the definition or criteria of systemic
      vasculitis including PAN or MPA will be changed.

PMID- 10078004
TI  - [Mixed connective tissue disease and overlap syndrome].
AB  - Clinical features of mixed connective tissue disease and overlap syndrome were
      described. Especially, importance of diagnosis and treatment in early stage of
      pulmonary hypertension in patients with MCTD were stressed.

PMID- 10078005
TI  - [Sjogren's syndrome].
AB  - Sjogren's syndrome(SS) is a chronic inflammatory disease characterized by
      keratoconjunctivitis sicca and xerostomia. According to the epidemiological
      survey done by the Japan Ministry of Health and Welfare(MHW) in 1994, about
      17,000 SS patients visit hospitals and the prevalence rate is approximately 0.06%
      for females. SS is diagnosed mainly by the criteria of MHW in 1977, and the
      revised ones will be published in the near future. Several candidates for the
      corresponding antigens for SS autoimmunity have discovered, such as alpha-fodrin
      and 203-211 amino acid residues of Ro/SSA-52 kDa. The sicca complex is treated
      with fluid replacement, but corticosteroids or immunosuppressive drugs are
      sometimes indicated in the treatment of extraglandular involvement. Several new
      drugs are now under investigation.

PMID- 10078006
TI  - [Fibromyalgia syndrome].
AB  - Fibromyalgia syndrome (FMS) is recognizable syndrome characterized by chronic,
      diffuse pain, an absence of inflammatory or structural muscloskeletal
      abnormalities, and a range of symptoms that include fatigue, and sleep and mood
      disturbances. Physical examination and laboratory testing are unrevealing, except
      for the presence of pain on palpation of characteristic soft-tissue sites, the
      tender points. Despite the recognition of FMS by the World Health Organization,
      it remains a controversial condition and its existence as a distinct entity
      remains uncertain. However, the concept of FMS is a useful one, allowing many
      investigations to be avoided and appropriate advice on treatment to be given. FMS
      may overlap with symptoms of, and the patient further impaired by, anxiety and
      depression. The term FMS dose not imply causation and merely describes the most
      common symptoms. Many patients with chronic fatigue syndrome(CFS) fulfill the
      criteria of FMS and represent one end of a spectrum of presentation. Evidence for
      triggering viral infection and the lower level of serum acylcarnitine, observed
      in CFS patients, is lacking in the majority of patients with FMS. These findings
      are suggestive to be distinctively another disorders between FMS and CFS.

PMID- 10078007
TI  - [Polymyalgia rheumatica].
AB  - Polymyalgia rheumatica (PMR) is a disease of unknown etiology characterized by
      severe myalgia and stiffness at shoulder girdle and pelvic girdle muscles and by
      normal serum creatine kinase levels. Marked elevation of erythrocyte
      sedimentation rate, acute onset within two weeks, and appearance in the aged are
      also additional characteristics of PMR. Ten to 50% of PMR patients have a
      concomitant temporal arteritis (TA)(giant cell arteritis). For the differential
      diagnoses of PMR, rheumatoid arthritis, polymyositis, fibromyalgia, malignancies,
      infections and depression should be considered. PMR without TA is treatable
      successfully with small amount of steroids (15-20 mg/day of prednisolone). For
      the PMR patients with TA should be treated with large amount of steroids (40-60
      mg/day of prednisolone) or steroid pulse therapy.

PMID- 10078008
TI  - [Behcet's disease].
AB  - Clinicopathologically, Behcet's disease is characterized by neutrophil and
      platlet hyperfunction. Lesions are formed presumably because neutrophils
      infiltrating the affected tissue release active oxygen and lysosomal enzymes in
      large amounts. The mechanisms of neutrophil hyperfunction was obscure, but in
      recent years attention has focused on the effects of cytokines released by
      mononuclear cells. As more has been learned about the etiopathogenesis of
      Behcet's disease, novel anti-inflammatory drugs, immunosuppressants, anti
      thrombotic agents, and anticoagulants have helped to achieve remarkable progress
      of treatment. Particularly notable is the effect on severe uveitis of
      cyclosporine, which is more effective than colchicine and conventional
      immunosuppressants. Low dose weekly methotrexate therapy might have a beneficial
      effect in the treatment of patients with neuro-Behcet's disease.

PMID- 10078009
TI  - [Antiphospholipid syndrome].
AB  - Antiphospholipid Syndrome (APS) was first described by Hughes and sometimes
      called as Hughes syndrome. Recent studies revealed that the antigen to
      anticardiolipin antibody (aCL) is not cardiolipin itself but co-factor beta 2-GPI
      which expresses its epitope when it combines cardiolipin or gets oxidized. Lupus
      Anticoagulant is now possibly considered as anti-prothrombin antibody. Livedo
      including Snedden syndrome, pulmonary hypertension and skin ulcer became
      considered as the part of symptoms of this disease. In ISAPA 1998, it is reported
      from several laboratories that IgA aCL is also pathogenic to thrombosis as well
      as IgG aCL. Atherosclerosis is also accelerated by aCL. Catastrophic APS is rare
      but fatal, reported 3 cases in Japan and 50 cases in the world.

PMID- 10078010
TI  - [Adult Still's disease].
AB  - Adult onset Still's disease was first reported by Bywaters in 1971. It is a
      systemic inflammatory disorder of unknown etiology, characterized by spiking
      fever, macular rash and polyarthritis. Although the prognosis is generally good,
      severe cases have been published. They include those with disseminated
      intravascular coagulation (DIC), hemophagocytosis, amyloidosis and respiratory
      failure. Among them, DIC is not uncommon. Prednisolone in a dose of 20-60 mg/day
      is required when patients fail to respond to nonsteroidal anti-inflammatory drugs
      (NSAIDs) or when they are accompanied by complications including pleuritis,
      pericarditis, liver dysfunction, severe arthritis and DIC. Recently, disease
      modifying antirheumatic drugs (DMARDs) and immunosuppressive agents including
      cyclophosphamide and methotrexate have been shown to be effective for alleviating
      refractory cases and chronic arthritis.

PMID- 10078011
TI  - [Recent advance in vasculitis syndrome].
AB  - Many classifications of vasculitis syndrome have been proposed. The American
      College of Rheumatology (ACR) proposed criteria for classification of vasculitis
      in 1990. In 1994, the nomenclature of systemic vasculitides was proposed by
      Chapel Hill International Consensus Conference. In this conference, the
      nomenclature of systemic vasculitides was discussed and confirmed by the
      committee consisted of 16 investigators from 6 countries. The classification of
      systemic vasculitides was proposed in concern with the size of involved artery
      and also with the appearance of antineutrophil cytoplasmic antibodies (ANCA). In
      Japan, Research committee of intractable vasculitis syndrome, Survey and Research
      on Specific Diseases, the Ministry of Health and Welfare of Japan proposed
      diagnostic criteria for vasculitis syndrome. The criteria for ANCA related
      vasculitis syndrome, temporal arteritis and antiphospholipid syndrome were
      proposed and a nation-wide survey has been undertaken in this committee
      (Chairman: Hiroshi Hashimoto). In this review, we describe a recent
      classification of vasculitides and recent topics on Takayasu arteritis, temporal
      arteritis, Wegener's granulomatosis and Churg-Strauss syndrome.

PMID- 10078012
TI  - [Pulmonary lesion associated with collagen vascular diseases: interstitial
      pneumonia].
AB  - Various pulmonary lesions can be found in patients with collagen vascular
      diseases. Not only the diseases but also treatment with various drugs relate to
      an occurrence of the pulmonary lesions such as infection, drug reaction,
      bronchiolitis and interstitial pneumonias. We focused on interstitial pneumonias
      based on our own experiences with patients whose lesions were diagnosed by
      surgical lung biopsy. Incidence of the interstitial pneumonias and diagnostic
      problems before biopsy using HRCT and BAL were evaluated. Comparison of
      interstitial pneumonias between idiopathic and associated with collagen vascular
      diseases is a problem to be solved.

PMID- 10078013
TI  - [Renal disorders in patients with collagen vascular diseases].
AB  - Membranous nephropathy, mesangial proliferative glomerulonephritis and renal
      amyloidosis are common renal pathology in RA patients. However, IgA nephropathy
      and diffuse thinning of glomerular basement membrane are described as common and
      characteristic renal lesions in Japanese RA patients. Glomerular filtration rate
      may decrease significantly in active lupus nephritis, but renal plasma flow does
      not change or even increase. These findings seem to be characteristic of SLE
      patients with active renal disorders. Therefore, filtration fraction may be a
      useful clinical parameter to evaluate SLE patients. Scleroderma renal crisis(SRC)
      has been believed to be the most serious renal disorder in systemic sclerosis
      (SSc). Recently, the presence of an antibody to RNA polymerase has been
      associated with a high prevalence of SRC.

PMID- 10078014
TI  - [Cardiovascular complications of collagen diseases].
AB  - Recent progress in the field of clinical epidemiology and diagnosis of major
      cardiovascular complications of collagen diseases were reviewed including
      systemic lupus erythematosus, systemic sclerosis, polymyositis.dermatomyositis,
      polyarteritis and mixed connective tissue disease. Major cardiac complications
      comprise pericarditis, myocardial disease, cardiac conduction system disease,
      coronary artery disease and valvular disease. Vascular complications comprise
      necrotizing vasculitis as a major organic involvement and Raynaud's phenomenon as
      a major functional involvement. Due to the recent development of sensitive
      methods of evaluating cardiovascular abnormalities, clinical diagnosing rate of
      cardiovascular complications in the early stage has been considerably increasing
      in patients with collagen diseases. On the other hand, number of patients with
      atherosclerotic cardiovascular complications due to long-term corticosteroid
      therapy has been also gradually increasing.

PMID- 10078015
TI  - [Central nervous system involvement in rheumatic diseases].
AB  - Among various rheumatic diseases, systemic lupus erythematosus and Behcet's
      disease are frequently complicated with serious neurological involvement, called
      CNS lupus and neuro-Behcet's syndrome (NB), respectively. CNS lupus includes
      lupus psychosis, such as organic brain syndrome and non-organic psychosis, as
      well as non-psychotic CNS lupus, such as epilepsy and focal lesions. Anti
      ribosomal P antibody is closely associated with lupus psychosis, whereas anti
      phospholipid antibodies appear to be involved in some manifestations of non
      psychotic CNS lupus. NB includes acute type and chronic progressive type. Acute
      NB is characterized by acute meningoencephalitis with focal lesions, which
      respond to steroid therapy. By contrast, chronic progressive NB is characterized
      by intractable slowly progressive dementia and/or psychosis with persistent
      elevation of cerebrospinal fluid IL-6 activity, which is resistant to
      conventional steroid therapy. However, recent studies suggest the efficacy of low
      dose methotrexate in chronic progressive NB.

PMID- 10078016
TI  - [Hematological manifestations].
AB  - Hematological manifestations as the clinicopathological features of connective
      tissue disease are described. Secondary anemia, so called anemia of chronic
      disorders (ACD), is one of the most common features of connective tissue disease.
      In addition, quantitative abnormalities of leukocytes or thrombocytes which
      reflect upon the pathophysiology of underlying connective tissue disease are
      variously observed. Patients with connective tissue disease sometimes develop
      hematological malignancies. Increased risk of lymphoma in Sjogren's syndrome has
      been known. The use of alkylating agents as immunosuppressive therapy is also
      associated with the risk of secondary or therapy-related myelodysplastic syndrome
      (MDS) and acute myeloid leukemia (AML). Pancytopenia or bicytopenia can be caused
      by hemophagocytosis which is related to connective tissue disease itself. Such
      condition is recognized as autoimmune-associated hemophagocytic syndrome (AAHS).
      Possible mechanism inducing hemophagocytosis, clinical features, diagnosis and
      treatment of AAHS are discussed.

PMID- 10078017
TI  - [Non-steroidal antiinflammatory drug--management of gastrointestinal
      complications and inhibition of COX-2].
AB  - Non-steroidal antiinflammatory drugs (NSAID) are widely used for the treatment of
      rheumatoid arthritis and other collagen vascular diseases, and now more than 30
      drugs are available. However, caution should be paid in using NSAIDs because of
      their serious side effects, especially gastrointestinal toxicity. Misoprostol has
      been shown to prevent NSAID-induced gastrointestinal damage, and proton-pump
      inhibitor omeprazole and misoprostol have been shown to be effective in the
      treatment of ulcers and erosions induced by NSAIDs. After the discovery of
      cyclooxygenase-2 (COX-2), investigators have raised a hypothesis that specific
      inhibitor of COX-2 should have anti-inflammatory activity with least
      gastrointestinal toxicity. According to this, efforts have been paid to produce
      COX-2 selective inhibitors. Although several COX-2 inhibitors have been reported
      to show reduced toxicity, further investigations are needed to establish their
      usefulness.

PMID- 10078018
TI  - [Synthetic glucocorticoid in the treatment of connective tissue diseases].
AB  - Synthetic glucocorticoids are the most potent anti-inflammatory and
      immunosuppressive drugs, which have been used for almost 50 years as a core drug
      for the treatment of connective tissue diseases. The mechanism of action of
      glucocorticoids as anti-inflammatory or immunosuppressive drug is considered as
      the repression of inflammatory cytokines, receptors of cytokines, and adhesion
      molecules. When 60 mg of prednisolone is administered in 3 divided doses, the
      plasma concentrations are around 20-30 micrograms/dl during the day time, in
      which condition around 90% of GC receptors are occupied. However, the
      concentration will decrease almost to 0 microgram/dl in the next early morning.
      In case of methyl prednisolone pulse therapy, about 40 micrograms/dl of the
      steroid is present in the next morning. These kinetics are important when we
      consider the glucocorticoid therapy. In the treatment of connective tissue
      diseases, the combination of the steroid therapy with the immunosuppressive
      therapy should always be considered. In diffuse proliferative lupus nephritis,
      glucocorticoid dosage, started at high level to suppress the clinical activity of
      SLE, decrease rather rapidly while cytotoxic drugs are administered at least for
      2 years. In the treatment of systemic sclerosis, normotensive scleroderma kidney
      is treated with moderate dose of glucocorticoid and cytotoxic drugs. It is our
      clinical impression that low dose glucocorticoid is quite effective in the
      treatment of rheumatoid arthritis. However, low dose glucocorticoid therapy is
      effective for the patient's sense of well-being, but is scarsely effective for
      the articular symptoms itself and shows intense rebound phenomenon when
      glucocorticoid is withdrawn.

PMID- 10078019
TI  - [Immunosuppressive treatment strategy in connective tissue diseases].
AB  - In this review, we summarized important articles published about
      immunosuppressive agents in connective tissue diseases. Intravenous
      cyclophosphamide therapy for lupus nephritis and oral cyclophosphamide therapy
      for Wegener's granulomatosis are major progress in past one decade. Newer
      immunosuppressive agents such as cyclosporin, tacrorimus are also introduced in
      steroid refractory organ involvements. And we discussed also the monitoring and
      prevention of adverse effects of immunosuppressive agents. This review will focus
      on immunosuppressive treatment strategy of connective tissue diseases.

PMID- 10078020
TI  - [Disease modifying anti-rheumatic drugs(DMARDs)].
AB  - Several kinds of disease modifying anti-rheumatic drugs (DMARDs) can be utilized
      for the treatment of patients with rheumatoid arthritis (RA) to expect the
      prevention of joint damage progression and the improvement of quality of life.
      However, the methodology for the use of DMARDs is still controversial. On the
      basis of our prospective study, earlier introduction of DMARDs can be more
      efficient for the suppression of active disease. Thus, for the patients with more
      than three swollen joints, high ESR and CRP, immediate prescription of DMARD is
      recommended. And if these situation will not change even 6 months after starting
      the therapy, we should make all possible efforts to lead patients into remission
      using DMARD or corticosteroids, which would prevent patients from disability of
      joint function and thus would improve the quality of life of patients with early
      RA.

PMID- 10078021
TI  - [Plasmapheresis for collagen diseases].
AB  - Recently plasmapheresis has been performed for connective tissue disease. Double
      filtration plasmapheresis (DFPP) has mainly been performed for rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SEL) since 1980. In DFPP,
      autoantibodies and immune complex are removed by the second filter. The
      adaptation of plasmapheresis is commonly for cases (1) which are resistant to
      some medications, (2) which have a high titer of antibodies or immune complex,
      (3) in which the medication must be decreased or stopped because of side effects
      and complications, or (4) which are in the acute active phase. We suggest DFPP to
      be useful as a treatment for connective tissue disease.

PMID- 10078022
TI  - [Gene therapy in autoimmune rheumatic diseases].
AB  - Several investigators have reported the possibility of gene therapy for
      experimental autoimmune diseases such as type-1 insulin-dependent diabetes
      (IDDM), experimental allergic encephalomyelitis (EAE), rheumatoid arthritis (RA),
      and systemic lupus erythematosus (SLE). Although there are no reports about gene
      therapies for human autoimmune rheumatic diseases including RA and SLE, we
      reviewed these experimental therapies for model animals and discussed the
      possibility of gene therapy for human autoimmune rheumatic disorders as a new
      therapeutic strategy.

PMID- 10078023
TI  - [Hepatitis C virus infection and cardiomyopathy].
AB  - The importance of hepatitis C virus (HCV) infection has been recently noted in
      patients with cardiomyopathies. HCV RNAs were found in the hearts of patients
      with cardiomyopathies, and negative strands of HCV RNA were also detected in the
      hearts, suggesting that HCV replicates in myocardial tissues. In a collaborative
      research project of the Committees for the Study of Idiopathic Cardiomyopathy,
      HCV antibody was more frequently found in patients with cardiomyopathies than
      that found in volunteer blood donors in Japan. HCV antibody was detected in 5.4%
      seeking care in 5 academic hospitals. Various cardiac abnormalities were found,
      and arrhythmias was the most frequent. These observations suggest that HCV
      infection is an important cause of a variety of otherwise unexplained heart
      diseases. It is likely that antiviral agents such as interferons and ribavirin
      will be valuable in the treatment of cardiomyopathy due to HCV infection.

PMID- 10078024
TI  - [High throughput gene analysis with DNA array--from sequencing to expression
      monitoring].
AB  - Proceedings of DNA array technology opened the way for the high throughput gene
      analysis, such as sequence analysis by hybridization (SBH) or gene expression
      monitoring. SBH, based on the ability to determine a DNA sequence by hybridizing
      oligonucleotide probes to the target DNA, appears to be a method with great
      potential for megabase sequencing. One of the most serious problems is that SBH
      requires extremely highly specific hybridization conditions which can
      discriminate one-base mismatches against a perfect match. We proposed new probe
      designs that contain several universal bases at both ends. By using these
      stacking probes, we could obtain not only strong hybridization signals, but also
      high discrimination values.

PMID- 10078025
TI  - [An excursion in the past. Quinine and other quina alkaloids. 2. The discovery of
      the basic structure of quinoline and quina alkaloids].

PMID- 10078026
TI  - [COX-1 and COX-2: functions and pharmacological effects].

PMID- 10078027
TI  - [New 4-quinolone derivatives in review].

PMID- 10078028
TI  - [Clinical and pathological studies on nemaline myopathy in adulthood].
AB  - We examined 22 biopsied muscles from adult patients who had the histopathological
      characteristics of nemaline myopathy. In the first group, 13 patients had muscle
      weakness and/or skeletal abnormalities, such as high-arched palate, pes cavus and
      scoliosis which are often accompanied with the congenital nemaline myopathy.
      Their appropriate diagnosis had never been made until muscle biopsy was done,
      because of benign clinical course. In the second group, the symptoms of nine
      patients became manifest in adulthood and failed to show typical skeletal
      abnormalities. However, six muscle biopsies showed the histopathologic
      characteristics of congenital nemaline myopathy; abnormal fiber type distribution
      including type 1 fiber predominancy, type 1 fiber atrophy and type 2B fiber
      deficiency. Three patients remained in good health until adulthood when they
      developed muscle weakness with pathologic findings of nemaline myopathy.
      Accordingly, nemaline myopathy in adulthood can be categorized into three forms;
      the first two forms have clinical and pathologic evidence of the congenital
      benign form, whereas the symptoms are too mild to be noticed. The third form is
      not a hereditary disorder which may result from autoimmune pathophysiology.

PMID- 10078029
TI  - [The usefulness of carotid artery ultrasonography in patients with Binswanger's
      encephalopathy].
AB  - Carotid artery ultrasonography (B-mode and Duplex method) was conducted in 49
      cases of Binswanger's encephalopathy (group B) to compare with 189 cases of
      lacunar infarction (group L). With B-mode method, there was no significant
      difference in the amount of plaque between group B and group L, but the inner
      diameter of the common carotid artery was greater in group B. Using Duplex
      method, we measured maximum systolic flow velocity (Max), minimum diastolic flow
      velocity (Min) and time velocity integral (TVI). We found that those data were
      consistently lower in group B than in group L, with a correlation to the severity
      of mental impairment. The decrease in Max in group B, which has diffuse
      arteriosclerosis, indicates a decline in cardiac function, while the decrease in
      Min indicates an increase of intracranial small vessel resistance. The lower TVI
      in group B is thought to reflect a loss of velocity in cerebrovascular
      circulation due to the decrease in Max and Min. Carotid artery ultrasonography
      thus proved useful in evaluating the pathogenesis and progression of the disease.

PMID- 10078030
TI  - [Slowly progressive aphemia--a case report].
AB  - A 69-year-old women was admitted to Tokyo Medical and Dental University Hospital
      because of slowly progressive difficulty in speech production over 8-years. On
      admission, her spontaneous speech was non-fluent, limited to one-syllable
      utterance, and severely efforty. But her visual and auditory comprehension was
      preserved. There was no significant general intellectual deterioration. Severe
      buccofacial apraxia, but no swallowing was observed. So we considered her
      difficulty in speech as aphemia. Three-dimensionally reconstructed surface MR
      image clearly showed severe atrophy in the posterior part of the left inferior
      frontal gyrus and the lower part of the left pre-central gyrus. The FDG-PET
      demonstrated a focal hypometabolism in the same region. The lesion in this area
      was suggested to be a cause of speech production difficulty in this case.

PMID- 10078031
TI  - [Serial MRI study on a case of anterior spinal artery syndrome].
AB  - A 63-year-old woman suddenly began to suffer from left chest pain. She gradually
      became unable to walk and was admitted to the emergency room at another hospital.
      When she became paraplegic in spite of steroid therapy, she was admitted to our
      hospital. Her affliction was diagnosed as anterior spinal artery syndrome because
      of flaccid paraplegia and dissociated sensory loss below the Th4 dermatome.
      Hematological study indicated a compensated DIC and hepatic enzyme abnormality,
      while the CSF examinations showed an elevation of protein and positive myelin
      basic protein (MBP) elevation. The initial MRI taken in the acute stage showed no
      abnormal signals on T1-weighted (T1) and Gd-enhanced images. The sagittal T2
      weighted image (T2) revealed central high intensity (HI) with longitudinal
      extension from Th2 through the Th11 vertebral level. On axial T2, HI was located
      on the gray matter at the Th3 and Th4 vertebral level, the ventral two-thirds at
      the Th8 vertebral level, the central ventral side at the Th9 and Th10 vertebral
      level, and the entire cross section at the Th12 and L1. A follow-up MRI
      examination showed that the range of HI on the sagittal T2 had been reduced to 5
      segments from Th6 through Th10 vertebral level. The T2 HI lesion on the axial
      aspect had become reduced so as to localize on the left ventral side at the Th8
      vertebral level and on the central ventral side at Th9 and Th10.

PMID- 10078032
TI  - [Myopathy with cerebral white matter abnormality--a case report].
AB  - A 45-year-old man noticed mild numbness of the feet at the age of 40 years and
      difficulty in standing up from squatting position at 43 years. His birth and
      developmental milestones were normal and the family history was unremarkable. He
      was alert and intelligent with global IQ of 91. There was mild muscle weakness as
      well as atrophy in bilateral hips and thighs. The serum creatine kinase level was
      542 U/l. On computed tomography, the hamstrings were preferentially involved. The
      biopsied specimens from the right quadriceps femoris and peroneal muscles showed
      myogenic changes with evidence of necrotic and regenerating process. Dystrophin,
      dystrophin-associated glycoproteins and merosin were normally expressed. From the
      clinical and pathologic findings, he was diagnosed as having myopathy. The
      electroencephalogram was normal but the P300 latency was prolonged. T2-weighted
      head magnetic resonance imaging showed diffuse high intensity in the cerebral
      white matter. Myopathy with cerebral white matter abnormality in adult patients
      has not yet been reported. Asymptomatic cerebral white matter abnormality should
      be considered in adult patients with myopathy.

PMID- 10078033
TI  - [An autopsy case of deep cerebral venous thrombosis: serial CT, MRI and
      pathological findings].
AB  - A 17-year-old girl developed vomiting of sudden onset, followed by a state of
      confusion that progressed rapidly to coma within one day. Laboratory tests
      indicated iron deficiency anemia and reactive thrombocytosis, but there was no
      evidence of coagulopathy. There was no history of medication including the
      contraceptive pill, either. Emergency CT scan without contrast enhancement showed
      increased density along the course of the vein of Galen and internal cerebral
      veins. A repeated CT scan without contrast enhancement carried out 24 hours after
      the onset of the illness confirmed extensive bilateral hypodensity of the
      thalami, basal ganglia and adjacent white matter. There was also a prominent
      spontaneous increase in the density of the deep cerebral venous system. MRI was
      performed 3 days after the onset of the illness, which showed absence of a flow
      void in the region of the internal cerebral veins and septal veins on T1-weighed
      images. T2-weighted images showed low intensity in these veins. At autopsy, the
      bilateral internal cerebral veins were occluded by fresh thrombosis and
      hemorrhagic infarction was seen in the bilateral thalami.

PMID- 10078034
TI  - [Excess caloric intake induced severe hypercapnia in a patient with Duchenne
      muscular dystrophy on noninvansive positive pressure ventilation].
AB  - In many patients with neuromuscular diseases, respiratory failure is mainly
      caused by alveolar hypoventilation in their terminal stages. Malnutrition is one
      of the common and serious problems in patients with chronic respiratory failure.
      Energy consumption for breathing is remarkably high in respiratory compromised
      patients, causing subsequent increase of total energy expenditure. However, most
      patients have limited capacity of oral intake. Nutritional depletion is
      associated with wasting of respiratory muscles, impairment of respiratory drive,
      alteration of respiratory pattern, and pathological change of pulmonary
      parenchyma. These indicate that nutritional and ventilatory support is very
      important in these patients. However, overfeeding also may have detrimental
      influence on respiratory failure. We experienced a Duchenne muscular dystrophy
      (DMD) patient on noninvasive positive pressure ventilation (NIPPV) who developed
      hypercapnia after total parenteral nutrition (TPN). Analysis of clinical course
      of this patient revealed that there is a significant correlation between PaCO2
      and caloric intake. Excess carbohydrate intake can precipitate fat synthesis
      which induces over-production of carbon dioxide (CO2). Since NIPPV doesn't have a
      closed circuit, there are some difficulties in respiratory management, such as
      air leakage to stomach and mouth, and airway obstruction. Failure to optimize
      NIPPV setting against increased CO2 load might cause hypercapnia in this patient.
      These suggest that evaluation of energy expenditure and design of nutritional
      program are essential to avoid hypercapnia due to nutritional support.

PMID- 10078035
TI  - [Adult-onset type II citrullinemia in a patient undergoing continuous ambulatory
      peritoneal dialysis].
AB  - A 57-year-old Japanese man was admitted to Toyama Medical & Pharmaceutical
      University Hospital with delirium and flapping tremor on April 2, 1997. He had
      been undergoing continuous ambulatory peritoneal dialysis (CAPD) because of
      diabetic nephropathy since 1993. Blood chemistry showed slightly elevated plasma
      ammonia level with no evidence of liver injury, and his portal venography
      revealed no port-systemic shunt. He was diagnosed as having type II citrullinemia
      because of an elevated citrulline level on amino acid analysis and very low
      hepatic argininosuccinate synthetase activity obtained from biopsy specimen of
      liver. In this case, plasma concentrations of ammonia and citrulline were not so
      high as those in previously reported cases, although the hepatic
      argininosuccinate synthetase activity was actually less than 10% of the control
      value. Owing to CAPD, he was conservatively controlled in a relatively good
      condition. This indicates that CAPD seems to be a useful therapeutic approach for
      citrullinemia since liver transplantation is still difficult in Japan.

PMID- 10078036
TI  - [Serial MRI findings in patients with CNS cryptococcosis].
AB  - We reported the serial magnetic resonance imaging (MRI) findings of two patients
      with central nervous system (CNS) cryptococcal infection without AIDS. The
      diagnosis of CNS cryptococcosis was made by visualizing the fungi in the CSF with
      the India ink test, detecting cryptococcal antigens, and culturing the fungus.
      Both patients had dilated perivascular Virchow-Robin (V-R) spaces, which were
      defined as small rounded lesions greater less than 3mm diameter that were
      hyperintense on T2-weighted images. They were present in the basal ganglia,
      brainstem and cerebral white matter. Case 1 had bilateral parietal arachnoid cyst
      which was thought to represent a focal collection of organisms and mucoid
      material within subarachnoid space. Abnormal optochiasmatic arachnoid enhancement
      detected in case 2, who had complete loss of vision. With disease progression
      perivascular V-R increased in size, resulting in the developing cryptococomas
      which were defined as rounded lesions greater than 3mm diameter, and were
      hyperintense on T2-weighted images in the basal ganglia, cerebellum and cerebral
      white matter. In follow-up MRI of those patients, radiological progression was
      seen despite appropriate treatment and falling CSF cryptococcal antigens. In
      conclusion, this spectrum of MRI appearances in CNS cryptococcosis reflects the
      pathological mechanism of invasion by the fungus, and may be relatively specific
      for cryptococcosis.

PMID- 10078037
TI  - [A case of spontaneous intracranial hypotension successfully treated with an
      epidural blood patch].
AB  - A 76-year-old woman was admitted to our hospital with complaints of a three-day
      history of severe postural headache without any apparent cause. Neurological
      examination revealed nuchal rigidity, and right auditory nerve paresis. Lumbar
      puncture yielded a low opening pressure of 50mmH2O and an elevated total protein
      up to 77mg/dl. Cranial magnetic resonance imaging (MRI) using gadolinium revealed
      diffuse dural enhancement, and effacement of the prepontine cistern. Spontaneous
      intracranial hypotension was strongly suspected, and to ascertain the presence of
      a cerebrospinal fluid (CSF) leak, radionuclide cisternography (RNC) was
      performed, which demonstrated a spinal CSF leak along the nerve root at the level
      of the lower lumbar spine. Interestingly, computed tomography-myelography (CTM)
      did not detect these abnormalities. An epidural blood patch with 15 ml of
      autologous blood at the L3-L4 interspace brought a dramatic symptomatic relief.
      Follow-up MRI, RNC, and CSF analysis demonstrated that the abnormal findings had
      disappeared. It is speculated that RNC is more sensitive for detecting small
      dural tears and CTM for anatomical anomalies including meningeal diverticula and
      perineural (Tarlov) cysts. We wish to stress, however, that RNC and CTM are
      complementary and sometimes interchangeable diagnostic modalities, and should be
      actively employed for detecting CSF leakage in SIH and for appropriate treatment.

PMID- 10078038
TI  - [A case of atypical Guillain-Barre syndrome exclusively showing multiple cranial
      nerve palsy with an elevation of anti-GQ1b and anti-GT1a IgG antibodies].
AB  - This is a case report of atypical Guillain-Barre syndrome (GBS). A 42-year-old
      woman displayed pharyngeal paralysis after a mild upper respiratory infection,
      subsequently having developed ophthalmoplegia, facial diplegia and accessory
      nerve palsy within about ten days. She had neither weakness nor abnormal tendon
      reflexes in the extremities. During the acute phase of the disease we found
      significant elevation of anti-GQ1b and anti-GT1a IgG antibodies in the serum, and
      immunoadsorption therapy had a remarkable effect on the symptoms. Although our
      case was extremely atypical of GBS in terms of exclusively showing multiple
      cranial nerve palsy and lacking areflexia, the elevation of anti-glycolipid
      antibodies during the acute phase suggests that this case shares pathogenesis
      with GBS.

PMID- 10078039
TI  - [Encephalopathy induced by fleroxacin in a patient with Machado-Joseph disease].
AB  - Convulsive seizure with unconciousness is an adverse effect of new quinolone
      antibiotics including fleroxacin. A block of GABA receptor in CNS has been
      reported as pathomechanism. A 48-year-old female patient with Machado-Joseph
      disease (MJD) had encephalopathy induced by fleroxacin. She revealed
      unconsciousness after the administration of fleroxacin (200mg/day) for three
      days. Electroencephrogram (EEG) showed diffuse slow waves. The administration was
      discontinued and her consciousness became clear after a day. The abnormal
      findings on EEG disappeared gradually. The concentrations of fleroxacin were
      within normal limits in serum and cerebrospinal fluid. The patient with MJD might
      have a tendency to develop encephalopathy by fleroxacin, because the GABA-ergic
      nervous system could be involved in MJD.

PMID- 10078040
TI  - [Bickerstaff's brainstem encephalitis with one-and-a-half syndrome].
AB  - We presented a case of Bickerstaff's brainstem encephalitis. A 50-year-old woman
      developed semicoma, external ophthalmoplegia, hyporeflexia, extensor plantar
      responses. A high titer of anti-GQ1b IgG antibody was detected in her acute phase
      serum. Auditory brainstem response suggested the presence of brainstem lesion.
      Although MRI and CSF showed no abnormality, one-and-a-half syndrome was observed
      during the clinical course, suggesting involvement of the pontine tegmentum. She
      received steroid pulse-therapy and symptoms disappeared completely. Our case
      suggested that anti-GQ1b IgG antibody might relate to the pathogenesis of
      intramedullary as well as extramedullary lesions.

PMID- 10078041
TI  - [Plasmapheresis in chronic inflammatory demyelinating polyradiculoneuropathy].

PMID- 10078042
TI  - [Prostheses in the mandible. The in-vivo measurements of mandibular deformation
      and the consequences for implant-anchored suprastructures].

PMID- 10078043
TI  - [Oscillating procedures in the preparation technic (I)].
AB  - An optimal preparation technique should meet the following requirements: a cavity
      that does not extend beyond the carious lesion; maximum preservation of sound
      tooth substance, preparation and margin design adapted to the requirements of the
      restorative material and its adhesion properties, prevention of adjacent tooth
      damage, and low technique sensitivity. Oscillating instruments with one diamond
      coated and one polished surface have been developed to overcome the limitations
      of conventional preparation designs dictated by rotary burs. Previously untreated
      carious lesions were prepared using a modified air-scaler handpiece (Sonicsys)
      with various working tips allowing interproximal cavity preparation with minimal
      extension and a low risk of damaging the neighboring tooth. Another oscillating
      system is based on the EVA-System. It uses files for the preparation of
      interproximal bevels and for the finishing of margins of interproximal box, crown
      and veneer preparations. These oscillating instruments overcome the major
      limitations of rotary burs for tooth preparation and facilitate conventional
      cavity preparation. In addition, they allow the use of cavity designs that could
      not be achieved with conventional instruments.

PMID- 10078044
TI  - [Roles of HPV genes in carcinogenesis].

PMID- 10078045
TI  - [Genome and proteins of rotavirus].

PMID- 10078046
TI  - [Cell tropism of HIV].

PMID- 10078047
TI  - [The molecular epidemiology of herpesvirus].

PMID- 10078048
TI  - [An introduction to the special section on "viral vaccines, their present and
      future"].

PMID- 10078049
TI  - [Efficacy of commercially available virus vaccines and their problems].

PMID- 10078050
TI  - [Factors affecting acceptance rate of measles vaccine].

PMID- 10078051
TI  - [Rotavirus vaccines as a model vaccine against enteric viral infections].

PMID- 10078052
TI  - [Induction of immune responses by DNA vaccine].

PMID- 10078053
TI  - [H 5 N1 avian influenza in Hong Kong].

PMID- 10078054
TI  - [The 50th anniversary of World Health Organization].

PMID- 10078055
TI  - [Current concept of schizophrenia: state of the art].
AB  - Approaches to diagnosing schizophrenia are different. There is a distinct
      tendency either to narrow the limits of the disease or to expand it, which in
      some cases leads to a disagreement and even a tendency to disputes. The
      comprehensive studies conducted in the Mental Health Research Center, Russian
      Academy of Medical Sciences, have provided an overall notion of the disease in
      terms of its progression and outcome. The clinical picture of schizophrenia is
      characterized by obligatory specific disorders, such as autism, reduced energy
      potential, emotional thinking, and behavioral disorders. Personality changes may
      be seen as the smoothening of specific personality traits and the appearance of
      the features that are not inherent to the patients in the past. Schizophernia is
      also characterized by positive psychopathological syndromes: pseudoneurotic,
      affective, psychopathy-like, hallucinatory-paranoid and catatonic. A study of
      7500 patients with schizophrenia demonstrated that there were clear-cut
      regularities in the development of the disease, which suggest that there are
      forms and types in its progression. The study identified 3 forms of development:
      continuous, recurrent, and attack-like progressive with varying degrees and rates
      of the process (severe, moderate, and mild). Genealogical and clinicogenetic
      studies demonstrated accumulation of psychoses and abnormal personalities in the
      families of probands, manifest and slowly progressive forms of schizophrenia and
      cases of schizoid psychopathy. Among the wide spectrum of pathogenetic concepts,
      priority should be given to the dopamine hypothesis, whose main point is
      accumulation of an excessive amount of dopamine in the brain tissue, especially
      in the nigrostriatal, mesocortical, and mesolimbic systems. This may lead to
      activation of dopaminergic brain structures with an increase of dopamine
      receptors. This hypothesis is confirmed by the neuropathological studies
      demonstrating a significant increase in the numerical density of the dendritic
      spines and dendritic trunks in the with layer of the prefrontal cortex. The
      highest index of the numerical density was observed in young patients with
      prevalent negative disorders. Inasmuch as there is no correlation of this index
      with the duration of the disease, it can be concluded that the abundance of
      synaptical connections is a result of disturbed brain development and a factor
      predisposing to severe progression of schizophrenia. Treatment modalities are
      determined by the form and rate of progression of and the pattern of the
      psychopathological syndrome. Of particular importance is the role of age, somatic
      state, and individual sensitivity to neuroleptic drugs. Another important factor
      in the treatment of schizophrenia is a simultaneous or consecutive impact on the
      psychopathological syndrome and the disease as a whole.

PMID- 10078056
TI  - [Quantitative EEG in early and differential diagnosis of mild dementia of
      different genesis].
AB  - Quantitative EEG was used to reveal the specific features of its amplitude
      frequency parameters and topography in patients with mild dementia of different
      genesis versus healthy elderly individuals. All four study groups of patients
      differ in EEC relative spectral density, they also differ from the healthy
      persons while alpharhythm was suppressed in Alzheimer's disease (AD) and vascular
      dementia (VD) and there was slower alpha-rhythm and higher theta-activity in
      senile AD (SAD). Patients with VD were characterized by desynchronized EEG.
      Factorial and stepwise discriminant analyses of EEG parameters showed that the
      control group greatly differed from patients with mild dementias. Patient groups
      mainly with atrophic atrophic AD and SAD or vascular (VD and mixed) dementia were
      also different whereas the mixed vascular-atrophic group is intermediate in EEC
      parameters between the VD group and the partially overlapped AD and SDA patient
      groups. Quantitative EEC data may be thus used for differential diagnosis to
      optimize therapy and prognosis even in mild dementia.

PMID- 10078057
TI  - [Brain dysfunction in subjects at risk of Alzheimer's disease].
AB  - Visual evoked potentials versus flash (VEP) and brain DC-potentials were studied
      in the first-order relatives of patients (mean age 42.6 +/- 1.6 years) with
      Alzheimer's disease (AD) and probands (mean age 60.9 +/- 0.9 years) and age
      matched healthy controls for the relatives and probands. In the relatives of AD
      patients, the latencies of N2, P3, N3 components were found to be delayed as
      compared with the controls. There was a delay in the latencies of the same
      components in the patients and their relatives, but it was smaller in the
      relatives of AD patients. The brain DC-potentials were higher in the relatives of
      AD patients than in the controls. Neurophysiological changes in the relatives of
      AD patients may be considered to be signs of latent neurodegeneration in the
      limbicoreticulocortical pathways, which may be associated with the excitotoxic
      processes and abnormal hyperactivity in the limbicoreticulocortical structures.

PMID- 10078058
TI  - [Brain isoforms of creatine kinase in health and mental diseases: Alzheimer's
      disease and schizophrenia].
AB  - The paper analyzes the authors' own findings and the data available in the
      literature on the intensity, site, and possible causes of impairment of the
      creatine-creatine phosphate system of brain energy metabolism in mental diseases,
      such as Alzheimer's disease (AD) and schizophrenia. Examining the level of
      cytosolic BB creatine kinase in postmortem AD and schizophrenic's brain
      structures showed a significant decrease in BB creatine kinase as compared with
      the similar control brain structures. There was the maximum decline in AD cases.
      It was considerable as compared with both the control and schizophrenic groups (p
      < 0.01). The decrement was revealed by various techniques, including the
      determination of activity, immunological responsiveness and the analysis of two
      dimensional protein maps. Immunocytochemical investigation indicated a decrease
      in responses to BB creatine kinase, mainly in astrocytes. The reduction in
      cytosolic BB creatine kinase levels is not a result of age, postmortem delay, or
      psychotic therapy. The causes of lower BB creatine kinase levels in the cell
      cytosol of the postmortem brain in mental pathology are discussed. The decrement
      in cytosolic BB creatine kinase in AD and schizophrenia occurs not only in the
      brain, but also in the peripheral tissues which contain BB creatine kinase. In
      all cases, it is greater in AD than in schizophrenia. Using immunosorbents with
      monoclonal antibodies to M-creatine kinase and to B-creatine kinase subunits
      makes it possible detect BB-creatine kinase in the extracts of human peripheral
      lymphocytes and platelets. A study of whether there is a relationship between the
      clinical data of mental patients and the level of BB creatine kinase in their
      blood elements is assumed to be useful in evaluating BB creatine kinase as a
      prognostic/diagnostic marker of mental diseases.

PMID- 10078059
TI  - [Nerve growth factor system in health and disease].
AB  - The biological effects of nerve growth factors (NGF) against the cells of the
      nervous, endocrine, and immune systems and the possible role of protein as an
      integral component of molecular communications between the above systems are
      studied. Based on analysis of the author's own findings, it is suggested that the
      impairment of regulatory mechanisms which is typical of the pathogenesis of some
      nervous and mental diseases is caused by diseases or at least accompanied by
      changes in the NGF system.

PMID- 10078060
TI  - [Neuronal death is basic problem of neurology and psychiatry].
AB  - The review deals with neuronal death in neurological and mental disorders. It
      considers two types of neuronal death in the central neuronal death: apoptosis
      and necrosis, as well as their mechanisms of development and regulation with the
      participation of apoptotic and antiapoptotic genes. At present, oxidative stress
      and excitotoxicity are considered to be the major mechanisms of cell death.
      Recent advances of molecular cell biology in the understanding the mechanisms
      responsible for neuronal death permit one to develop new therapeutical approaches
      in diseases of the central nervous system.

PMID- 10078061
TI  - [Genetic basis for Alzheimer's disease and other dementias and prospects of
      molecular diagnosis].
AB  - Dementias are diseases of progressive memory loss and intellectual impairment in
      adults. Alzheimer's disease (AD) amounts to 50-80% of all forms of dementias in
      middle-aged and elderly individuals. AD includes several clinical and genetic
      subtypes characterized by the common pattern of specific cerebral hallmarks.
      Aging and genetic factors are the most important risk factors predisposing to AD.
      Three gene-bearing mutations for AD have been identified. These included
      presenilin 1, presenilin 2, and amyloid precursor protein (APP). In addition, the
      polymorphic isoform of apolyprotein E e4 gene has been found to be a genetic risk
      factor for some forms of familial and sporadic AD. Other genes for AD are to be
      identified. The genetic loci or mutations in genes leading to several other
      neurodegenerative diseases and dementia have been also discovered. These genetic
      achievements contribute to the development of markers for the presymptomatic
      diagnosis of dementias and the development of transgenic models in vitro and in
      vivo for rational therapy of these dramatic diseases.

PMID- 10078062
TI  - [Epidemiology and risk factors of Alzheimer's disease].
AB  - Alzheimer's disease or dementia of the Alzheimer's type (AD/DAT) is one of the
      most common dementia conditions and it amounts to over 40-90% of dementia cases
      among elderly and old patients. Epidemiological studies in this area make a great
      contribution to the study of the etiology and risk factors of AD/DAT). The
      collaborative reanalysis of AD/DAT prevalence and incidence in EEC countries
      ("EURODERM" programme) shows that the overall European age-specific prevalence of
      AD does not differ greatly. There was an exponential increase in age-specific
      AD/DAT prevalence was found with age, as evidenced by the studies made in Russia.
      Sex-specific prevalence and incidence of AD/DAT are unclear since the fact that
      the condition more often occurs in elderly women than in men of the same age has
      not been confirmed. The data on risk factors obtained in cohort and case-control
      studies of AD/DAT have been analyzed. Progress in molecular genetics has
      identified 3 genes that are responsible for the occurrence of familial forms of
      the disease. The gene of apolipoprotein E on chromosome 19 is recognized to be
      the major genetic risk factor of late AD/DAT. The role of gene mutations in the
      trigger mechanisms of sporadic BA/DAT is also discussed. The environmental risk
      factors of AD/DAT include brain injury, viral infections, neutroxic chemicals,
      various immunological and hormonal disorders. The protective role of such factors
      as long-term use of nonsteroid antiinflammatory agents and estrogens is
      discussed. The involvement of nicotine dependence in the pathogenesis and the
      role of smoking as a possible protective factor are the subject of discussion.
      Such factors as education levels, occupation, stresses are widely discussed,
      although their role is considered to be controversial. The Russian study revealed
      the influence of chronic stress on AD development. The authors consider that
      chronic stress may play an important role in AD/DAT progression.

PMID- 10078063
TI  - [Discriminant analysis of clinical laboratory data for diagnosis and treatment of
      tuberculosis and lung cancer].
AB  - The study is based on the clinical observation and examination of 33 patients
      with stages 1 or 2 lung cancer (Group 1), 53 with stage 3 lung cancer (Group 2),
      and 44 patients with pulmonary tuberculosis (Group 3). All the patients underwent
      surgical treatment. A control group comprised 50 apparently healthy individuals.
      The clinical laboratory studies included general peripheral blood analysis of
      ESR, the levels of hemoglobin, leukocytes, lymphocytes, total protein and
      albumin. ANOVA revealed a highly significant (p < 0.00004) differences in 5 of
      the 6 study laboratory parameters, variations in the level of total protein
      between the groups did not differ from that in the groups (p = 0.25). ANOVA
      revealed significant covariation of the levels of protein with ESR (p < 0.00004)
      and those of albumin (p < 0.00004). When variations in the latter were
      eliminated, the effect of the groups on total protein variation was highly
      significant (p = 0.0018). Discriminant analysis showed that the parameters
      studied were of diagnostic value in the differential diagnosis: probabilities of
      correct subdivision of patients ranged 72.6 to 78%, those of erroneous
      classification being 27.4 and 22%, respectively. The actual probabilities of
      misclassification were twofold lower. The problems in the employment of the
      discriminant procedure in the differential diagnosis of the study diseases using
      the specific contingent principle are discussed and a specific clinical
      observation is cited as an example.

PMID- 10078064
TI  - [Pathogenesis of systemic hemodynamic disorders and choice of optimal obstetrical
      strategy in pregnant patients with gestosis].
AB  - A total of 810 pregnant women were examined in order to elucidate the
      pathogenesis of hemodynamic disorders in gestosis. The main group consisted of
      460 patients with gestosis of different severity and the control group included
      150 women with uneventful pregnancy. Central and regional hemodynamics in normal
      pregnancy were studied in detail by modern diagnostic methods (echocardiography
      and dopplerometry) and the relationship between the detected shifts and the
      function of the utero-placento-fetal circulation was shown. The predominant type
      of central hemodynamics in gestosis is the hypokinetic. Disorders in renal and
      cerebral circulation contribute to the pathogenesis of severe gestosis.
      Pathogenetic variants of hemodynamics shifts in gestosis are analyzed and
      recommendations on the follow-up of pregnancy are offered. Indications for
      preterm delivery in the interests of the mother and fetus are defined.

PMID- 10078065
TI  - [Significance of bibliographic state standards for scientific publications].
AB  - The paper discusses the significance of bibliographic description standards for
      exchange of scientific information. Special attention is paid to the most typical
      mistakes made in bibliographic description, which are most common in references
      to scientific papers.

PMID- 10078066
TI  - Progress towards poliomyelitis eradication Pakistan, 1994-1998.

PMID- 10078067
TI  - Yellow fever, Bolivia.

PMID- 10078069
TI  - Apical mural thrombus: technical pitfalls.
AB  - A left ventricular thrombus can occur in a variety of clinical settings and, when
      small, may be difficult to document. Understanding the clinical scenarios of when
      these thrombi form and how to optimise echocardiographic scanning techniques will
      increase the sensitivity and specificity of the examination (tables 1 and 2).

PMID- 10078068
TI  - Central role of echocardiography in the diagnosis and assessment of heart
      failure. British Society of Echocardiography.

PMID- 10078070
TI  - Quality issues for echocardiography in the community.

PMID- 10078072
TI  - Reconsidering quality.

PMID- 10078071
TI  - Echocardiography in adult congenital heart disease.

PMID- 10078073
TI  - Ablate and pace: a pragmatic approach to paroxysmal atrial fibrillation not
      controlled by antiarrhythmic drugs.

PMID- 10078074
TI  - Stamps in cardiology. Antismoking campaigns.

PMID- 10078075
TI  - Importance and implications of the occurrence of AV block following
      radiofrequency ablation.

PMID- 10078076
TI  - Mechanisms of fetal tachycardia.

PMID- 10078077
TI  - Sudden death in hypertrophic cardiomyopathy: potential importance of altered
      autonomic control of vasculature.
AB  - Current evidence suggests that alterations in the autonomic function and abnormal
      vascular control play a significant role either as independent triggers
      themselves or as modifiers of ischaemia and tolerance to to arrhythmias. A
      combination of several factors--that is, arrhythmia, hypotension, altered
      autonomic function including vascular control, and ischaemia are therefore likely
      to act as triggers for sudden death. The relative contribution of each of these
      factors needs further detailed study.

PMID- 10078078
TI  - Stents are used too often.

PMID- 10078079
TI  - Atrioventricular nodal ablation and implantation of mode switching dual chamber
      pacemakers: effective treatment for drug refractory paroxysmal atrial
      fibrillation.
AB  - OBJECTIVE: To assess the effect of atrioventricular node ablation and
      implantation of a dual chamber, mode switching pacemaker on quality of life,
      exercise capacity, and left ventricular systolic function in patients with drug
      refractory paroxysmal atrial fibrillation. PATIENTS: 18 consecutive patients with
      drug refractory paroxysmal atrial fibrillation. METHODS: Quality of life was
      assessed before and after the procedure using the psychological general wellbeing
      index (PGWB), the McMaster health index (MHI), and a visual analogue scale for
      cardiac symptoms. Nine of the patients also underwent symptom limited exercise
      tests and echocardiography to assess left ventricular systolic function. RESULTS:
      The procedure allowed a reduction in antiarrhythmic drug treatment (p < 0.01).
      PGWB and symptom scores improved (p < 0.01) but the MHI score did not change.
      Left ventricular systolic function and exercise capacity were unchanged.
      CONCLUSIONS: Atrioventricular node ablation and implantation of a DDDR/MS
      pacemaker is effective treatment for refractory paroxysmal atrial fibrillation,
      producing improved quality of life while allowing a reduction in drug burden. The
      popularity of the treatment is justified, but further studies are needed to
      determine optimum timing of intervention.

PMID- 10078080
TI  - Predictors of atrial rhythm after atrioventricular node ablation for the
      treatment of paroxysmal atrial arrhythmias.
AB  - OBJECTIVE: To assess the natural history of the atrial rhythm of patients with
      paroxysmal atrial arrhythmias undergoing atrioventricular node ablation and
      permanent pacemaker implantation. DESIGN AND SETTING: A retrospective cohort
      study of consecutive patients identified from the pacemaker database and
      electrophysiology records of a tertiary referral hospital. PATIENTS: 62
      consecutive patients with paroxysmal atrial arrhythmias undergoing
      atrioventricular node ablation and permanent pacemaker implantation between 1988
      and July 1996. MAIN OUTCOME MEASURES: (1) Atrial rhythm on final follow up ECG,
      classified as either ordered (sinus rhythm or atrial pacing) or disordered
      (atrial fibrillation, atrial flutter or atrial tachycardia). (2) Chronic atrial
      fibrillation, defined as a disordered rhythm on two consecutive ECGs (or
      throughout a 24 hour Holter recording) with no ordered rhythm subsequently
      documented. RESULTS: Survival analysis showed that 75% of patients progressed to
      chronic atrial fibrillation by 2584 days (86 months). On multiple logistic
      regression analysis a history of electrical cardioversion, increasing patient
      age, and VVI pacing were associated with the development of chronic atrial
      fibrillation. A history of electrical cardioversion and increasing patient age
      were associated with a disordered atrial rhythm on the final follow up ECG.
      CONCLUSIONS: Patients with paroxysmal atrial arrhythmias are at high risk of
      developing chronic atrial fibrillation. A history of direct current
      cardioversion.

PMID- 10078081
TI  - Electrocardiographic measures of ventricular repolarisation dispersion in
      patients with coronary artery disease susceptible to ventricular fibrillation.
AB  - OBJECTIVE: To study electrocardiographic measures of ventricular repolarisation
      dispersion in patients prone to ventricular fibrillation compared with controls
      matched for the extent of coronary heart disease and the use of beta blockers.
      DESIGN: A case-control study. SETTING: Cardiovascular laboratory of a tertiary
      referral centre. PATIENTS: Fifty patients with documented ventricular
      fibrillation not associated with acute myocardial infarction, and their controls
      matched for sex, age, number of diseased coronary vessels, left ventricular
      ejection fraction, previous myocardial infarction and its location, and the use
      of beta blockers. MAIN OUTCOME MEASURES: Electrocardiographic measures of QT, JT,
      and Tend interval dispersions in a 12 lead electrocardiogram. RESULTS: The
      ventricular fibrillation patients compared to controls showed increased mean (SD)
      QTapex dispersion (53 (18) ms v 44 (18) ms, respectively; p < 0.01) and mean (SD)
      Tend dispersion (46 (17) ms v 38 (15) ms, respectively; p < 0.05). CONCLUSIONS:
      Increased QTapex and Tend dispersions are associated with a susceptibility to
      ventricular fibrillation even when the extent of the coronary heart disease and
      use of beta blockers are taken into consideration. However, because of a
      considerable overlap between the groups, measures of QT dispersion assessed from
      a 12 lead electrocardiogram do not provide clinically useful information for
      identification of patients at risk of sudden cardiac death.

PMID- 10078082
TI  - Differential effects of defibrillation on systemic and cardiac sympathetic
      activity.
AB  - OBJECTIVE: To assess the effect of defibrillation shocks on cardiac and
      circulating catecholamines. DESIGN: Prospective examination of myocardial
      catecholamine balance during dc shock by simultaneous determination of arterial
      and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were
      applied in 30 patients after initiation of ventricular fibrillation for a routine
      implantable cardioverter defibrillator test. Another 10 patients were externally
      cardioverted (50-360 J) for atrial fibrillation. MAIN OUTCOME MEASURES:
      Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after
      the shock. RESULTS: After internal shock, arterial noradrenaline increased from a
      mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while
      coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01),
      reflecting a shift from cardiac net release to net uptake. After external shock
      delivery, there was a similar increase in arterial noradrenaline, from 260 (112)
      to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained
      unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01),
      outlasting the threefold rise following internal shock (p = 0.001). In both
      groups, a negative transmyocardial adrenaline gradient at baseline decreased
      further, indicating enhanced myocardial uptake. Cardiac lactate production
      occurred after ventricular fibrillation and internal shock, but not after
      external cardioversion, so the neurohumoral changes resulted from the
      defibrillation process and not from alterations in oxidative metabolism.
      CONCLUSIONS: A dc shock induces marked systemic sympathoadrenal and
      sympathoneuronal activation, but attenuates cardiac sympathetic activity. This
      might promote the transient myocardial depression observed after electrical
      discharge to the heart.

PMID- 10078083
TI  - Superiority of ibutilide (a new class III agent) over DL-sotalol in converting
      atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study
      Group.
AB  - OBJECTIVE: To compare the efficacy and safety of a single dose of ibutilide, a
      new class III antiarrhythmic drug, with that of DL-sotalol in terminating chronic
      atrial fibrillation or flutter in haemodynamically stable patients. DESIGN:
      Double blind, randomised study. SETTING: 43 European hospitals. PATIENTS: 308
      patients (mean age 60 years, 70% men, 48% with heart disease) with sustained
      atrial fibrillation (n = 251) or atrial flutter (n = 57) (duration three hours to
      45 days) were randomised to three groups to receive a 10 minute infusion of 1 mg
      ibutilide (n = 99), 2 mg ibutilide (n = 106), or 1.5 mg/kg DL-sotalol (n = 103).
      Infusion was discontinued at termination of the arrhythmia. MAIN OUTCOME MEASURE:
      Successful conversion of atrial fibrillation or flutter, defined as termination
      of arrhythmia within one hour of treatment. RESULTS: Both drugs were more
      effective against atrial flutter than against atrial fibrillation. Ibutilide was
      superior to DL-sotalol for treating atrial flutter (70% and 56% v 19%), while the
      high dose of ibutilide was more effective for treating atrial fibrillation than
      DL-sotalol (44% v 11%) and the lower dose of ibutilide (44% v 20%, p < 0.01). The
      mean (SD) time to arrhythmia termination was 13 (7) minutes with 2 mg ibutilide,
      19 (15) minutes with 1 mg ibutilide, and 25 (17) minutes with DL-sotalol. In all
      patients, the duration of arrhythmia before treatment was a predictor of
      arrhythmia termination, although this was less obvious in the group that received
      2 mg ibutilide. This dose converted almost 48% of atrial fibrillation that was
      present for more than 30 days. Concomitant use of digitalis or nifedipine and
      prolongation of the QTc interval were not predictive of arrhythmia termination.
      Bradycardia (6.5%) and hypotension (3.7%) were more common side effects with DL
      sotalol. Of 211 patients given ibutilide, two (0.9%) who received the higher dose
      developed polymorphic ventricular tachycardia, one of whom required direct
      current cardioversion. CONCLUSION: Ibutilide (given in 1 or 2 mg doses over 10
      minutes) is highly effective for rapidly terminating persistent atrial
      fibrillation or atrial flutter. This new class III drug, under monitored
      conditions, is a potential alternative to currently available cardioversion
      options.

PMID- 10078084
TI  - Fetal tachycardias: management and outcome of 127 consecutive cases.
AB  - OBJECTIVE: To review the management and outcome of fetal tachycardia, and to
      determine the problems encountered with various treatment protocols. STUDY
      DESIGN: Retrospective analysis. SUBJECTS: 127 consecutive fetuses with a
      tachycardia presenting between 1980 and 1996 to a single tertiary centre for
      fetal cardiology. The median gestational age at presentation was 32 weeks (range
      18 to 42). RESULTS: 105 fetuses had a supraventricular tachycardia and 22 had
      atrial flutter. Overall, 52 fetuses were hydropic and 75 non-hydropic. Prenatal
      control of the tachycardia was achieved in 83% of treated non-hydropic fetuses
      compared with 66% of the treated hydropic fetuses. Digoxin monotherapy converted
      most (62%) of the treated non-hydropic fetuses, and 96% survived through the
      neonatal period. First line drug treatment for hydropic fetuses was more diverse,
      including digoxin (n = 5), digoxin plus verapamil (n = 14), and flecainide (n =
      27). The response rates to these drugs were 20%, 57%, and 59%, respectively,
      confirming that digoxin monotherapy is a poor choice for the hydropic fetus.
      Response to flecainide was faster than to the other drugs. Direct fetal treatment
      was used in four fetuses, of whom two survived. Overall, 73% (n = 38) of the
      hydropic fetuses survived. Postnatally, 4% of the non-hydropic group had ECG
      evidence of pre-excitation, compared with 16% of the hydropic group; 57% of non
      hydropic fetuses were treated with long term anti-arrhythmics compared with 79%
      of hydropic fetuses. CONCLUSIONS: Non-hydropic fetuses with tachycardias have a
      very good prognosis with transplacental treatment. Most arrhythmias associated
      with fetal hydrops can be controlled with transplacental treatment, but the
      mortality in this group is 27%. At present, there is no ideal treatment protocol
      for these fetuses and a large prospective multicentre trial is required to
      optimise treatment of both hydropic and non-hydropic fetuses.

PMID- 10078085
TI  - Ventriculo-atrial time interval measured on M mode echocardiography: a
      determining element in diagnosis, treatment, and prognosis of fetal
      supraventricular tachycardia.
AB  - OBJECTIVE: To determine whether M mode echocardiography can differentiate fetal
      supraventricular tachycardia according to the ventriculo-atrial (VA) time
      interval, and if the resulting division into short and long VA intervals holds
      any relation with clinical presentation, management, and fetal outcome. DESIGN:
      Retrospective case series. SUBJECTS: 23 fetuses with supraventricular
      tachycardia. MAIN OUTCOME MEASURES: A systematic review of the M mode
      echocardiograms (for VA and atrioventricular (AV) interval measurements),
      clinical profile, and final outcome. RESULTS: 19 fetuses (82.6%) had
      supraventricular tachycardia of the short VA type (mean (SD) VA/AV ratio 0.34
      (0.16); heart rate 231 (29) beats/min). Tachycardia was sustained in six and
      intermittent in 13. Hydrops was present in three (15.7%). Digoxin, the first drug
      given in 14, failed to control tachycardia in five. Three of these then received
      sotalol and converted to sinus rhythm. All fetuses of this group survived.
      Postnatally, supraventricular tachycardia recurred in three, two having Wolff
      Parkinson-White syndrome. Four fetuses (17.4%) had long VA tachycardia (VA/AV
      ratio 3.89 (0.82); heart rate 226 (10) beats/min). Initial treatment with digoxin
      was ineffective in all, but sotalol was effective in two. Heart failure caused
      fetal death in one and premature delivery in one. All three surviving fetuses had
      recurrences of supraventricular tachycardia after birth: two had the permanent
      form of junctional reciprocating tachycardia and one had atrial ectopic
      tachycardia. CONCLUSIONS: Careful measurement of ventriculo-atrial intervals on
      fetal M mode echocardiography can be used to distinguish short from long VA
      supraventricular tachycardia and may be helpful in optimising management.
      Digoxin, when indicated, may remain the drug of choice in the short VA type but
      appears ineffective in the long VA type.

PMID- 10078086
TI  - Recovery pattern of left ventricular dysfunction following radiofrequency
      ablation of incessant supraventricular tachycardia in infants and children.
AB  - OBJECTIVE: To assess recovery pattern of left ventricular function secondary to
      incessant tachycardia after radiofrequency ablation in a group of infants and
      children. DESIGN AND SETTING: A combined prospective and retrospective
      echocardiographic study carried out in a tertiary paediatric cardiac centre.
      PATIENTS: Echocardiographic evaluation of left ventricular size and function in
      nine children with incessant tachycardia, before and after successful
      radiofrequency ablation. Age at ablation ranged from 2 months to 12.5 years (mean
      4.1 years). Recovery of left ventricular function was analysed in relation to age
      at ablation (group I < 18 months, group II > 18 months). MAIN OUTCOME MEASURE:
      Ventricular recovery pattern. RESULTS: Seven of the nine children had left
      ventricular dysfunction; six of these also had left ventricular dilatation. All
      children with left ventricular dysfunction had normalisation of ejection fraction
      and fractional shortening; left ventricular dilatation also improved, but the
      improvement occurred after recovery of function. There was a shorter recovery
      time for left ventricular function in younger (group I) than in older children
      (group II) (mean (SD) 5.7 (7.2) months v 31.3 (5.2) (p < 0.002). CONCLUSIONS:
      Tachycardia induced cardiomyopathy is reversible following curative treatment
      with radiofrequency. Recovery of left ventricular systolic function precedes
      recovery of left ventricular dilatation. Time course to recovery is shorter in
      younger children.

PMID- 10078087
TI  - Images in cardiology. Congenital morphologies of the aortic valve.

PMID- 10078088
TI  - Quality of life in chronic heart failure: cilazapril and captopril versus
      placebo. Cilazapril-Captopril Multicentre Group.
AB  - OBJECTIVE: To measure quality of life (QOL) in patients with mild to moderate
      heart failure treated with angiotensin converting enzyme (ACE) inhibitors
      cilazapril or captopril. DESIGN: Randomised, double blind, placebo controlled,
      parallel groups trial. SUBJECTS: 367 patients with New York Heart Association
      (NYHA) heart failure class II (62%), III (36%) or IV (1%). METHODS: Patients were
      randomised to receive cilazapril 1 mg daily (n = 191) or captopril 25 mg three
      times daily (n = 90) for 24 weeks, or placebo for 12 weeks followed by cilazapril
      1 mg daily for a further 12 weeks (n = 86). If patients had not responded after
      four weeks cilazapril was increased to 2.5 mg daily and captopril to 50 mg three
      times daily. QOL was assessed at baseline, 12, and 24 weeks using the sickness
      impact profile (SIP), the profile of mood states (POMS), the Mahler index of
      dyspnoea-fatigue, and a health status index (HSI). RESULTS: The physical
      dimension of the SIP averaged 7 units at baseline and improved after 12 weeks by
      2.24 units in the cilazapril group, 2.38 units in the captopril group, and 1.51
      units in the placebo group. The difference between drug and placebo was therefore
      0.73 units (95% CI -0.86 to 2.32) for cilazapril, and 0.87 units (95% CI -0.96 to
      2.70) for captopril, with small non-significant effect sizes (a statistical
      method for estimating the importance of a treatment related change) of 0.12 and
      0.14. Similar results were observed for the total POMS and HSI scores. Although
      QOL improved more on the ACE inhibitors than on placebo, the effect sizes were
      not significant (< or = 0.26). CONCLUSIONS: Improvements in QOL in mild to
      moderate heart failure were small when treated with cilazapril or captopril
      compared with placebo.

PMID- 10078090
TI  - Minimally invasive aortic valve replacement through a transverse sternotomy: a
      word of caution.
AB  - OBJECTIVES: To compare aortic valve replacement (AVR) using a minimally invasive
      approach through a transverse sternotomy with the established approach of median
      sternotomy. DESIGN: Retrospective, case-control study. PATIENTS: Fourteen high
      risk patients (median age 78, Parsonnet score of 18%) who underwent AVR performed
      through a minimally invasive transverse sternotomy were compared with a
      historical group of patients matched for age, sex, and Parsonnet score who
      underwent AVR performed through a median sternotomy by the same surgeon. OUTCOME
      MEASURES: Cross clamp time, total bypass time, intensive care stay, postoperative
      in-hospital stay, morbidity, and mortality. RESULTS: There were two deaths in the
      minimally invasive group and none in the control group (NS). The cross clamp and
      total bypass times were longer in the minimally invasive group (67 and 92 minutes
      v 46 and 66 minutes, p < 0.001). There was a higher incidence of re-exploration
      for bleeding (14% v 0%) and paravalvar leaks (21% v 0%) in the minimally invasive
      group but these differences were not significant. The minimally invasive group
      had a longer postoperative in-hospital stay (p = 0.025). The incidence of
      mortality or major morbidity was 43% (six of 14) in the minimally invasive group
      and 7% (one of 14) in the matched pairs (p = 0.013). CONCLUSIONS: AVR can be
      performed through a transverse sternotomy but the operation takes longer and
      there is an unacceptably high incidence of morbidity and mortality.

PMID- 10078089
TI  - Cardiac autoimmunity in HIV related heart muscle disease.
AB  - OBJECTIVE: To assess the frequency of circulating cardiac specific autoantibodies
      in HIV positive patients with and without echocardiographic evidence of left
      ventricular dysfunction. SUBJECTS: 74 HIV positive patients including 28 with
      echocardiographic evidence of heart muscle disease, 52 HIV negative people at low
      risk of HIV infection, and 14 HIV negative drug users who had all undergone non
      invasive cardiac assessment were studied along with a group of 200 healthy blood
      donors. RESULTS: Cardiac autoantibodies detected by indirect immunofluorescence
      (serum dilution 1/10) were more common in the HIV positive patients (15%),
      particularly the HIV heart muscle disease group (21%), than in HIV negative
      controls (3.5%) (both p < 0.001). By ELISA (dilution 1/320), abnormal anti-alpha
      myosin autoantibody concentrations were found more often in HIV patients with
      heart muscle disease (43%) than in HIV positive patients with normal hearts (19%)
      or in HIV negative controls (3%) (p < 0.05 and p < 0.001, respectively). Anti
      alpha myosin autoantibody concentrations were greater in HIV positive patients
      than in HIV negative controls, regardless of cardiac status ((mean SD) 0.253
      (0.155) v 0.170 (0.076); p = 0.003). In particular the mean antibody
      concentration was higher in the HIV heart muscle disease patients (0.291 (0.160)
      v 0.170 (0.076); p = 0.001) than in HIV negative controls. On follow up, six
      subjects with normal echocardiograms but raised autoantibody concentrations had
      died after a median of 298 days, three with left ventricular abnormalities at
      necropsy. This compared with a median survival of 536 days for 21 HIV positive
      patients with normal cardiological and immunological results. CONCLUSIONS: There
      is an increased frequency of circulating cardiac specific autoantibodies in HIV
      positive individuals, particularly those with heart muscle disease. The data
      support a role for cardiac autoimmunity in the pathogenesis of HIV related heart
      muscle disease, and suggest that cardiac autoantibodies may be markers of the
      development of left ventricular dysfunction in HIV positive patients with normal
      hearts.

PMID- 10078091
TI  - Validation of an automated technique for determining the mechanical
      characteristics of coronary arteries during balloon angioplasty: laboratory
      assessment with necropsy segments.
AB  - OBJECTIVES: To develop a technique for automatic inflation of a percutaneous
      transluminal coronary angioplasty (PTCA) balloon, with continuous measurement of
      the balloon pressure and volume; to validate the technique for determining the
      mechanical characteristics of coronary arteries. METHODS: During necropsy
      examination of the hearts of nine patients, 17 coronary artery samples were
      obtained for histological examination. A PTCA balloon was inserted into each
      artery, and the balloon pressure and volume were measured continuously during
      four repeat automatic inflations of the balloon. RESULTS: Of the 17 arteries,
      eight showed elastic, six plastic, and three fracture pressure-volume deformation
      characteristics. For the plastic deformations, the first inflation required a
      higher pressure than subsequent repeat inflations of 82 (61) kPa (mean (SD),
      range 25 to 175 kPa). For the three in the fracture group, the pressure drop
      because of the fracture occurred between 210 and 540 kPa. Two of these three
      showed a tear on visual inspection, and the other showed disruption of the
      intimal plaque on blinded histological examination. Of the six with plastic
      deformation characteristics alone, one showed a tear, and on histological
      examination two others showed splitting of the internal and external elastic
      lamina and one showed separation of intima and media. None in the elastic group
      showed any of these characteristics. CONCLUSIONS: Plastic and fracture
      deformation characteristics could be differentiated from elastic characteristics.
      Visual or histological evidence of fracturing was present in all three arteries
      identified during angioplasty as having pressure-volume fracture characteristics.

PMID- 10078092
TI  - Evaluation of technician supervised treadmill exercise testing in a cardiac chest
      pain clinic.
AB  - OBJECTIVE: To determine the efficacy and safety of trained cardiac technicians
      independently performing treadmill exercise stress tests as part of the
      assessment of patients with suspected angina pectoris. DESIGN: Retrospective
      comparison of 250 exercise tests performed by cardiac technicians and 225 tests
      performed by experienced cardiology clinical assistants (general practitioners
      who perform regular NHS cardiology duties), and consultant cardiologists over the
      same time period. SETTING: Regional cardiac centre with a dedicated cardiac chest
      pain clinic. PATIENTS: All patients were referred by their general practitioners
      with a history of recent onset of chest pain, which was suspected to be angina
      pectoris. OUTCOME MEASURES: Peak workload achieved, symptoms, indications for
      termination, complications. RESULTS: The diagnostic yield of technician
      supervised tests (percentage positive or negative) was similar to that of
      medically supervised tests (76% v 69%, NS). The average peak workload achieved by
      patients was less by 1.2 mets (p < 0.005). This was probably due to more tests
      being terminated earlier due to chest pain and ST segment depression in the
      technician group compared with doctors (10% and 16% v 5% and 11% respectively, p
      = 0.06 and 0.07). One patient in the technician supervised group developed a
      supraventricular tachycardia during the recovery phase of the exercise test.
      CONCLUSIONS: Technician supervised stress testing is associated with a high
      diagnostic rate and low complication rate in patients with suspected ischaemic
      heart disease. Its efficacy is comparable to tests supervised by experienced
      doctors and its use should be encouraged.

PMID- 10078093
TI  - Atrioventricular block occurring several months after radiofrequency ablation for
      the treatment of atrioventricular nodal re-entrant tachycardia.
AB  - Atrioventricular (AV) block following radiofrequency (RF) ablation for the
      treatment of AV nodal re-entrant tachycardia (AVNRT) is a rare but well
      recognised complication of the procedure--the reported incidence ranges from 1%
      to 21%. Almost all cases of AV block occur during or shortly after the procedure,
      are transient, and recover quickly. Two patients (a 22 year man and a 72 year old
      woman) with symptomatic AV block occurring several months after slow pathway RF
      ablation, requiring permanent pacemaker implantation, are described. Both
      patients had had several 24 hour Holter recordings before the procedure, and in
      neither case was there any evidence of intermittent or persistent AV block. This
      is a rare complication with no definitive predictors; however, all efforts should
      be made to exclude AV block in patients presenting with suggestive symptoms
      following RF ablation. With the wide use of RF ablation for the treatment of
      AVNRT, more cases are likely to occur. A registry should allow documentation of
      the incidence of this complication.

PMID- 10078094
TI  - Images in cardiology. Rapid progression of pericardial malignant mesothelioma.

PMID- 10078095
TI  - Cardiac involvement in proximal myotonic myopathy.
AB  - Proximal myotonic myopathy (PROMM) is a recently described autosomal dominantly
      inherited disorder resulting in proximal muscles weakness, myotonia, and
      cataracts. A few patients with cardiac involvement (sinus bradycardia,
      supraventricular bigeminy, conduction abnormalities) have been reported. The
      cases of three relatives with PROMM (weakness of neck flexors and proximal
      extremity muscles, calf hypertrophy, myotonia, cataracts) are reported: a 54 year
      old man, his 73 year old mother, and 66 year old aunt. All three presented with
      conduction abnormalities and one had repeated, life threatening, sustained
      monomorphic ventricular tachycardia. This illustrates that severe cardiac
      involvement may occur in PROMM.

PMID- 10078096
TI  - Congenitally corrected transposition of the great arteries in an 80 year old
      woman.
AB  - Congenitally corrected transposition of the great arteries (CCTGA) is a rare form
      of congenital heart disease characterised by atrioventricular as well as
      ventriculoarterial discordance. It is usually associated with a variety of severe
      intracardiac defects. Few patients with this abnormality survive past 50 years.
      An 80 year old woman was admitted to the hospital because of mild congestive
      heart failure. Cardiac examination revealed a 4/6 holosystolic and a 2/6
      decrescendo diastolic murmur at the left sternal border. Radiography,
      echocardiography, and computed tomography confirmed newly diagnosed CCTGA without
      associated intracardiac defects.

PMID- 10078097
TI  - Transcatheter occlusion of a post-Fontan residual hepatic vein to pulmonary
      venous atrium communication using the Amplatzer septal occluder.
AB  - A residual hepatic vein to left atrial communication may result in progressive
      cyanosis after the Fontan procedure. This problem has usually been treated
      surgically by ligation or re-inclusion of the residual hepatic vein in the Fontan
      circulation. Previous attempts at transcatheter closure of such veins have been
      unsuccessful. An Amplatzer septal occluder was successfully used for
      transcatheter closure of a post-Fontan hepatic vein to pulmonary venous atrium
      fistula in an 8 year old boy.

PMID- 10078098
TI  - Supravalvar aortic stenosis: unexpected findings at surgery.

PMID- 10078099
TI  - Sinus bradycardia and multiple episodes of sinus arrest following administration
      of ibutilide.

PMID- 10078100
TI  - Septal ablation in a patient with hypertrophic obstructive cardiomyopathy and a
      unique variant of anomalous origin of the left coronary artery.

PMID- 10078101
TI  - Imaging the thoracic aorta in the injured patient.

PMID- 10078102
TI  - HER-2/neu testing comes of age.

PMID- 10078103
TI  - Factor V Leiden: death and DNA.

PMID- 10078104
TI  - Recommendations for the reporting of pancreatic specimens containing malignant
      tumors. The Association of Directors of Anatomic and Surgical Pathology.
AB  - The Association of Directors of Anatomic and Surgical Pathology has developed
      recommendations for the surgical pathology report for common malignant tumors.
      The recommendations for malignant tumors of the pancreas are reported herein.

PMID- 10078105
TI  - HER-2/neu oncogene amplification by fluorescence in situ hybridization in
      epithelial tumors of the ovary.
AB  - HER-2/neu gene amplification and protein overexpression have been associated with
      prognosis in breast, lung and prostate cancers but have not been extensively
      studied in ovarian carcinoma. For the study, we selected 5-micron-thick, formalin
      fixed, paraffin-embedded tissue sections from 74 cases of ovarian epithelial
      tumors of low malignant potential and ovarian carcinoma. Tumors were graded and
      staged and evaluated for amplification of the HER-2/neu gene by fluorescence in
      situ hybridization. HER-2/neu amplifications was present in 3 of 13 serous,
      mucinous, and endometrioid epithelial tumors of low malignant potential and in 40
      of 61 epithelial carcinomas. In the carcinoma group, amplification did not
      correlate with stage, grade, or tumor type. Mean follow-up was 31 months; 1
      patient with a low malignant potential tumor and 32 patients with carcinomas died
      of disease. On univariate and multivariate analysis, survival correlated with
      stage of disease but not with HER-2/neu amplification. HER-2/neu amplification by
      fluorescence in situ hybridization can be performed on tissue sections of ovarian
      neoplasms; amplification is uncommon in ovarian tumors of low malignant
      potential, but is present in 66% of ovarian epithelial carcinomas. HER-2/neu
      amplification did not predict outcome in ovarian epithelial neoplasia but may
      have an important role in tumor development.

PMID- 10078106
TI  - Fine-needle aspiration of cystic lesions of the kidney. Morphologic spectrum and
      diagnostic problems in 41 cases.
AB  - Although imaging studies show the nature of most cystic lesions of the kidney
      (RCs), many RCs require fine-needle aspiration (FNA) for accurate diagnosis.
      Interpretation of the FNAs remains challenging. The FNA specimens of 41 RCs were
      reviewed and correlated with imaging studies. Final diagnoses for 30
      cytologically benign lesions were simple cyst (28), acquired cystic kidney (1),
      and cystic renal carcinoma (1). The fluid from the benign cysts displayed
      macrophages, epithelial cells from the cyst lining, tubular cells, neutrophils,
      and Liesegang rings. Fluid from the acquired cystic kidney and the cystic renal
      cell carcinoma showed features similar to those of the benign cysts. The 9 cases
      with "suspicious" cytology included 5 complex cystic lesions displaying rare but
      atypical epithelial cell clusters, 3 low-grade renal cell carcinomas with many
      mildly atypical papillary clusters of epithelial cells, and 1 simple benign cyst
      with many tubular cells. The 2 cytologically malignant lesions were cystic renal
      cell carcinomas with abundant tumor cells with partially clear cytoplasm and
      atypical nuclei admixed with abundant macrophages and lymphocytes; 1 case
      developed in a kidney with acquired cystic disease. Simple cysts remain the most
      frequently aspirated RCs, but complex cystic lesions are increasingly recognized.
      Since many RCs are composed of independent loculi, a nonrepresentative sample is
      a potential problem, and cytologic-radiologic correlation becomes mandatory. The
      "suspicious" patterns identified in this study should serve as diagnostic
      guidelines and set the foundation for future validation.

PMID- 10078107
TI  - Use of cultured cells as a control for quantitative immunocytochemical analysis
      of estrogen receptor in breast cancer. The Quicgel method.
AB  - Variation in tissue fixation, processing, and staining is largely responsible for
      poor reproducibility of estrogen receptor (ER) immunohistochemistry assays. A
      frozen, agar-suspended pellet of MCF-7 cells with known ER content was added to
      each of 55 samples of invasive breast carcinoma (IBC), serving as a control.
      Image analysis determined percentages of positive area (positive nuclei per total
      nuclei analyzed) and positive stain (sum of optical density of the positive
      nuclear area divided by sum of the optical density of all nuclei studied) of MCF
      7 cells and IBC. MCF-7 cells had a mean value of 150 fmol/mg of ER by dextran
      coated charcoal analysis. Image analysis of MCF-7 cells included with the 55
      cases showed a mean positive area of 70.81. Positive staining from the IBC cases
      ranged from 0 to 98.5. By using the known ER content and the positive area of the
      MCF-7 cells, a conversion factor was used to translate the positive area of the
      clinical specimens to a femtomole equivalent, which for the 55 IBCs ranged from 0
      to 1,790 (mean, 187). Inclusion of a control with known femtomole quantity of ER
      provides an internal standard for quality control and ER quantitation.

PMID- 10078108
TI  - Clinicopathologic features and genetic alterations in endometrioid carcinoma of
      the uterus with villoglandular differentiation.
AB  - Serious and endometrioid carcinomas differ dramatically in their clinical
      behavior; however, the specific significance of villoglandular (papillary)
      differentiation in endometrioid carcinoma has been studied rarely. We compared
      the clinicopathologic features and genetic alterations in 28 villoglandular
      endometrioid carcinomas compared with 60 nonvilloglandular endometrioid
      carcinomas and 60 healthy women. The study revealed a slight increase in the
      frequency of early-stage disease in villoglandular tumors compared with
      nonvilloglandular tumors. No differences were observed in the age at onset or
      cellular grade. The oncogene and susceptibility gene analyses revealed a positive
      association of K-ras oncogene mutation and germline variants of the cytochrome P
      450 1A1 (CYP1A1) gene and an inverse association of the p53PIN3 variant with
      villoglandular carcinomas, whereas no differences were observed in the c
      erbB2/neu oncogene amplification or the methylenetetrahydrofolate reductase
      germline variant. Finally, a positive association was found between CYP1A1 and
      methylenetetrahydrofolate reductase variants and the presence of papillary
      differentiation in the myometrial component. The results suggest that the
      villoglandular differentiation pattern arises without aggressive
      clinicopathologic features in a genetic background of transforming and carcinogen
      metabolism genes, characteristic of estrogen-related endometrial tumors (type 1)
      not exhibiting an unfavorable prognosis.

PMID- 10078109
TI  - Focal-segmental glomerulosclerosis. The relationship between tubular atrophy and
      segmental sclerosis.
AB  - Biopsy specimens with focal-segmental glomerulosclerosis (FSGS) show segmental
      sclerosis (SS) and tubular atrophy (TA). The relationship between SS and TA was
      studied using serial sections. Based on the location of the SS, 3 and 5 biopsy
      specimens, respectively, were classified as FSGS, glomerular tip lesion (GTL) or
      FSGS, not otherwise specified (NOS). The proximal tubule was classified as normal
      or atrophic. The glomerulus was tracked through serial sections in both
      directions and classified as normal, SS (graded 1(+)-4+), or ischemic. Segmental
      sclerosis was identified in 21 of 24 glomeruli in FSGS, GTL and in 46 of 89
      glomeruli in FSGS, NOS; TA was identified in 13 of 16 glomeruli in FSGS, GTL and
      6 of 13 glomeruli in FSGS, NOS, which showed 1+ SS, and in 36 of 38 glomeruli in
      both forms, which showed 2+ to 3+ SS. Basement membrane disruptions at the
      glomerular-tubular junction and interstitial expansion with inflammation was
      encountered. Three biopsy specimens with FSGS, NOS had hypertensive changes and
      showed TA in several normal and in all ischemic glomeruli. Chronic tubular injury
      is present in most glomeruli containing segmental lesions, even small lesions,
      suggesting that the glomerular and tubular injury may have a common cause or that
      tubular injury may result from constituent(s) in the glomerular filtrate.

PMID- 10078110
TI  - Disparate surgical margin lengths of colorectal resection specimens between in
      vivo and in vitro measurements. The effects of surgical resection and formalin
      fixation on organ shrinkage.
AB  - We noticed almost routine disparate results in margin lengths when colorectal
      specimens are measured in vivo by the surgeon and in vitro by the pathologist. We
      studied 26 sigmoid and rectum specimens to document the amount of organ shrinkage
      after surgical removal and fixation. Each specimen had a 5.0-cm segment at each
      end of the specimen marked by serosal sutures before vascular devitalization. The
      segments were measured after the specimen sat unfixed for 10 to 20 minutes and
      after 12 to 18 hours of formalin fixation. The segments shrank to a median length
      of 3.0 cm (40% of the in vivo length) after 10 to 20 minutes and an additional
      0.85 cm, to a median length of 2.15 cm, after fixation. Overall after fixation,
      the segments shrank 57% of the in vivo length. Approximately 70% of the shrinkage
      occurred during the first 10 to 20 minutes after removal, and the remaining 30%
      occurred after fixation. For optimal accuracy, margin distance must be obtained
      immediately after surgical removal. Once the specimen has been removed for
      several minutes, the difference between unfixed and fixed margin lengths is 30%.
      A correction factor of approximately 2x should be applied when interpreting the
      margin length.

PMID- 10078111
TI  - The use of subcutaneous fat tissue for amyloid typing by enzyme-linked
      immunosorbent assay.
AB  - The amyloidoses are biochemically heterogeneous diseases with pathophysiologic
      deposits of various proteins. The clinical course, prognosis, and therapy are
      different for each type of amyloidosis and, therefore, a type-specific diagnosis
      is demanded as early as possible. We describe a method for typing the most common
      systemic amyloidoses of AL, AA, and transthyretin types by enzyme-linked
      immunosorbent assay (ELISA), using abdominal wall subcutaneous fat biopsy
      specimens. The method was tested on 21 abdominal fat biopsy specimens that were
      sent to the laboratory. Of these, 15 contained amyloid that was successfully
      characterized in 14 cases. One specimen contained amyloid that did not react with
      any antisera used. The 6 specimens without amyloid gave no reaction in ELISA. The
      described ELISA method is reliable and easy to perform, and the tissue sample
      needed is obtained by minor surgery.

PMID- 10078112
TI  - Diagnostic usefulness of antineutrophil cytoplasmic autoantibody serology.
      Comparative evaluation of commercial indirect fluorescent antibody kits and
      enzyme immunoassay kits.
AB  - Antineutrophil cytoplasmic autoantibodies (ANCAs) are increasingly used as
      serologic markers for pauci-immune crescentic glomerulonephritis and small vessel
      vasculitis. Many hospital laboratories and referral laboratories use commercial
      assay kits to detect ANCAs, despite inadequate documentation in the medical
      literature of kit performance. We evaluated the diagnostic sensitivity,
      specificity, and predictive value of 3 commercial indirect immunofluorescence
      assay (IFA) kits and 7 commercial enzyme immunoassay (EIA) kits for several ANCA
      subtypes. Serum samples from 396 patients with a variety of renal diseases were
      analyzed, including 146 patients with pauci-immune crescentic glomerulo-nephritis
      with or without systemic vasculitis. With 1 exception, the kits had more than 90%
      agreement with the reference standard and gave results similar to those of
      research laboratories. IFA diagnostic sensitivity ranged from 81% to 91% and EIA
      sensitivity from 75% to 84%. Maximum specificity was obtained with combined IFA
      and EIA. Diagnostic specificity was more than 70% for 2 of 3 IFA kits and at
      least 90% for 5 of 7 EIA kits. Predictive values varied with clinical
      manifestations. Most commercial IFA and EIA kits that were evaluated provide
      acceptably accurate analytic results.

PMID- 10078113
TI  - Untreated chronic lymphocytic leukemia concurrent with or followed by acute
      myelogenous leukemia or myelodysplastic syndrome. A report of five cases and
      review of the literature.
AB  - Although it has been known that patients with chronic lymphocytic leukemia (CLL)
      have a higher frequency of second malignant neoplasms, the development of acute
      myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in these patients is
      extremely rare. Most reported cases have been therapy-related. In this article,
      we report the clinical and immunophenotypic features of 5 cases of untreated CLL
      concurrent with or followed by the development of AML or MDS. All 5 patients were
      men, with ages ranging from 57 to 87 years (mean, 73.8 years). Four patients had
      AML and 1 patient had refractory anemia with ringed sideroblasts. In the 4 cases
      of AML and CLL, 2 distinct cell populations (i.e., myeloblasts and lymphocytes)
      were identified morphologically and/or immunophenotypically. Our findings support
      that this rare concurrence of AML or MDS and untreated CLL may represent 2
      separate disease processes.

PMID- 10078114
TI  - Relative frequencies and sites of presentation of lymphoid neoplasms in a
      community hospital according to the revised European-American classification.
AB  - Relative frequencies for common subtypes in the revised European-American
      classification of lymphoid neoplasms (REAL classification) have been reported. We
      determined the relative frequencies and sites of presentation of REAL subtypes at
      a 700-bed community hospital in central Illinois. A database was used to identify
      and prospectively catalogue all newly diagnosed lymphoid neoplasms from July 1,
      1995 to March 1, 1998. The approach to diagnosis and subtyping incorporated
      morphologic features, immunophenotype, and clinical findings according to
      criteria proposed in the REAL classification. Of 347 lymphoid neoplasms
      diagnosed, 319 were subtyped in the REAL classification. Of these, 261 were B
      cell neoplasms, 21 were T-cell neoplasms, and 37 were Hodgkin disease variants.
      Chronic lymphocytic leukemia/small lymphocytic lymphoma/prolymphocytic leukemia,
      diffuse large cell, and follicle center neoplasms were the most common B-cell
      subtypes. Large granular lymphocyte leukemia was the most common T-cell neoplasm.
      Nodular sclerosis was the most common Hodgkin disease variant. The relative
      frequencies in a US community hospital setting are similar to those reported in
      other studies. Differences are attributable to patient selection criteria, study
      group geographic location and racial composition, and/or referral patterns.
      Diverse REAL classification subtypes may be expected in US community hospitals.

PMID- 10078115
TI  - Evaluation of a new reagent for preserving fresh blood samples and its potential
      usefulness for internal quality controls of multichannel hematology analyzers.
AB  - We describe a new, easy-to-use reagent, Cyto-Chex (Streck Laboratories, Omaha,
      Neb), that preserves fresh whole blood in a non-cross-linking, nonformalin
      manner. Target values assigned to fresh blood were essentially met after
      preservation and storage of up to 31 days. Respective mean analytic inaccuracies
      and short-term intra-assay coefficients of variation (n = 30) were as follows:
      WBCs, 6.7% and 1.99%; RBCs, 0.7% and 0.76%; hemoglobin, -1.8% and 0.79%;
      hematocrit, -0.3% and 0.75%; mean corpuscular volume, -1.0% and 0.78%; and
      platelets, 6.9% and 3.12%. Linearity of dilution-sensitive analytes was
      satisfactory over a wide range of dilutions after preservation of blood samples.
      Ten independent laboratories using 10 different instruments determined day-to-day
      interassay imprecision during four 7-day periods after blood preservation. Mean
      interassay coefficients of variation for participating laboratories were WBC,
      1.92%; RBC, 1.00%; hemoglobin, 1.29%; hematocrit, 2.00%; and platelets 3.29%.
      Cyto-Chex enables long-term monitoring of instrument accuracy and precision with
      retained blood specimens of healthy persons. Blood from patient cohorts with
      various hematologic disorders and with a wide range of numeric abnormalities
      and/or parameter aberrations can be preserved satisfactorily with this reagent.
      The reanalysis of preserved patient blood samples is an important adjunct to the
      use of commercial control material in quality control programs of multichannel
      hematology analyzers.

PMID- 10078116
TI  - Strategies for the early diagnosis of acute myocardial infarction using
      biochemical markers.
AB  - We evaluated different diagnostic strategies for the early diagnosis of acute
      myocardial infarction, combining sensitivity and specificity of different markers
      evaluated singly and using combination testing in parallel and serial modes.
      Myoglobin, cardiac troponin I (TnI), creatine kinase (CK), and CK-MB mass were
      tested in blood samples from 26 patients with acute myocardial infarction
      collected at admission (T0; mean = 3.3 hours from the onset of chest pain) and 3
      and 6 hours later. The comparison group was made up of 70 patients with renal
      failure, skeletal muscle diseases, stable angina, unstable angina, and chest pain
      of nonischemic origin. Single tests showed different sensitivities in relation to
      the different release kinetics; myoglobin was the most sensitive (69% at T0)
      although less specific (46%), and TnI showed the highest specificity (90%) and a
      sensitivity of 54%. Combination testing in a parallel mode using myoglobin and
      TnI or CK-MB had the same sensitivity and specificity as myoglobin tested singly.
      The best combination in a serial mode is myoglobin and TnI (at T0 sensitivity,
      54%; specificity, 98%), as confirmed by the analysis of the positive predictive
      value, the negative predictive value, and the accuracy evaluated as a function of
      different disease prevalences.

PMID- 10078117
TI  - Suppression of total digoxin concentrations by digoxin-like immunoreactive
      substances in the MEIA digoxin assay. Elimination of negative interference by
      monitoring free digoxin concentrations.
AB  - Digoxin-like immunoreactive substances (DLIS) cross-react with antidigoxin
      antibody and falsely elevate immunoassay-measured total digoxin concentrations.
      The fluorescence polarization immunoassay (FPIA) for digoxin showed high cross
      reactivity with DLIS, but a new microparticle enzyme immunoassay (MEIA) had low
      cross-reactivity. The concentration of digoxin in the presence of DLIS was
      falsely lowered (negative interference) when measured by MEIA. We prepared the
      following serum pools: 2 normal (no DLIS), 2 from patients with uremia, and 3
      from patients with liver disease (high DLIS). No patients received digoxin or
      digitoxin. When normal pools were supplemented with known concentrations of
      digoxin, total and free concentrations measured by both assays were comparable,
      but when liver and uremic pools containing high DLIS were supplemented with
      digoxin, the measured total digoxin concentrations were lower by MEIA and higher
      by FPIA. However, by taking advantage of 25% protein binding of digoxin and high
      protein binding of DLIS, free digoxin levels were not affected by DLIS. In 2
      patients receiving digoxin but without volume expansion, total and free digoxin
      concentrations measured by both assays were comparable; in the 2 volume-expanded
      patients, only free digoxin concentrations were comparable. Monitoring free
      digoxin concentration can eliminate negative interference of DLIS in the MEIA for
      digoxin.

PMID- 10078118
TI  - Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary
      thromboembolic disease using an improved method for factor VLeiden detection.
AB  - Activated protein C resistance caused by factor VLeiden mutation is the most
      common inherited predisposing cause of venous thromboembolism, including
      pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is
      higher among patients with PE evident at autopsy than in the general population.
      Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed
      pulmonary thromboembolic disease during a 4-year period were collected for DNA
      extraction. Extraction and molecular analysis of the DNA was performed with an
      improved technique with an internal control to determine the presence of factor
      VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who
      were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no
      homozygotes for factor VLeiden mutation were identified. This yielded a positive
      rate of 6% overall and 7% among white patients, which is similar to the incidence
      of heterozygotes in the white population. This study indicates that routine
      determination of factor VLeiden mutation is not warranted for patients with PE
      diagnosed at autopsy.

PMID- 10078119
TI  - Binding of von Willebrand factor to collagen by flow cytometry.
AB  - We developed a new method for the detection of large von Willebrand factor (vWf)
      multimers binding to collagen and for the determination of vWf antigen (vWf:Ag)
      using flow cytometry. Collagen is coated on to polystyrene beads, allowing
      detection of found large vWf multimers. In addition, rabbit antibody against vWf
      is coated on to the beads allowing detection of all vWf:Ag. In plasma samples
      from healthy persons and patients (with type 1, 2A, 2N, or severe von Willebrand
      disease or hemophilia), 4 different assays were performed: vWf:Ag by
      immunoelectrophoresis; vWf ristocetin cofactor (vWf:RCof); CBA; and vWf:Ag based
      on an enzyme-linked immunosorbent assay using polystyrene beads. We assayed the
      flow cytometric method using 2 bead sizes. The optimal bead size was 3.136
      microns. The results of CBA and vWf:Ag closely correlated with those of vWf:RCof
      and vWf:Ag (immunoelectrophoresis), respectively, and showed a low limit of
      detection. Interassay variance of cytometric methods was lower than interassay
      variance of traditional assays. In addition, we used the new assays to monitor
      desmopressin therapy.

PMID- 10078120
TI  - Crafting a useful surgical pathology report.

PMID- 10078121
TI  - Never say never.

PMID- 10078122
TI  - Reasonable care.

PMID- 10078123
TI  - Disorders of the cervical spine.

PMID- 10078124
TI  - Anterior and posterior cervical spine fusions. 1964.

PMID- 10078125
TI  - Pathology of ossification of the posterior longitudinal ligament and ligamentum
      flavum.
AB  - Ossification takes place in the posterior longitudinal ligament and ligamentum
      flavum of the spine under certain conditions of unknown nature. Ossification of
      these ligaments has the following characteristics: (1) ectopic bone formation
      occurring within the spinal ligaments; (2) ossification accompanies ligamentous
      tissue hyperplasia and cell proliferation; (3) before ossification,
      fibrocartilaginous cell proliferation, calcification and tissue resorption with
      vascular ingrowth take place sequentially; (4) ossification of the ligament has a
      specific site of predilection and often occurs in combination with senile
      ankylosing vertebral hyperostosis (Forestier's disease) or diffuse idiopathic
      skeletal hyperostosis; and (5) ossification and symptom development are
      remarkably more frequent in the Japanese population. Recent studies revealed that
      bone morphogenetic proteins and transforming growth factor-beta played an
      important role in the matrix hyperplasia and ossification of the spinal ligament,
      and metabolic and genetic aberration often characterized patients suffering from
      this disorder.

PMID- 10078126
TI  - Anterior floating method for cervical myelopathy caused by ossification of the
      posterior longitudinal ligament.
AB  - Ossification of the posterior longitudinal ligament lessens the sagittal diameter
      of the cervical canal and compresses the spinal cord anteriorly, and may produce
      severe disabling myelopathy. The anterior floating method is one of the anterior
      decompression and reconstructions used in the treatment of cervical myelopathy
      caused by ossification of the posterior longitudinal ligament. This procedure
      consists of subtotal resection of vertebral bodies and discs, with slight
      thinning and release of the ossified ligament using air instrumentation. This is
      followed by reconstruction of the cervical spine using autogenous strut bone
      graft accompanied by postoperative application of a halo vest. This method is
      indicated for patients who present with moderate or severe myelopathies, and
      especially in those where the canal narrowing ratio exceeds 60%. This radical
      procedure causes decompression of the spinal cord and restores its function by
      enlarging the neural canal with anterior migration of the ossified ligament. The
      procedure minimizes the extent of surgical invasions and avoids damage to the
      neural tissue, because it does not require the removal of the ossification of the
      posterior longitudinal ligament. It also stops postoperative regrowth of the
      ossification. The operative results with long term followup indicate a 71%
      average recovery rate based on the criteria established by the Japan Orthopedic
      Association.

PMID- 10078127
TI  - Expansive laminoplasty for myelopathy in ossification of the longitudinal
      ligament.
AB  - Laminectomy, which had long been used for treatment of cervical spondylotic
      myelopathy, including ossification of the longitudinal ligament in the cervical
      spine, had numerous complications such as postoperative malalignment of the
      cervical spine and vulnerability of the spinal cord caused by total removal of
      the posterior structures. In 1977 Hirabayashi devised an open door expansive
      laminoplasty, which is a relatively easier and safer procedure than laminectomy,
      that eliminated such problems by preserving the posterior elements. The
      decompression effect of the expansive laminoplasty against a compressed spinal
      cord is comparable with that of laminectomy and anterior decompression followed
      by fusion, whereas the expansive laminoplasty has no structural problems and
      adverse effects on adjacent disc levels that often are associated with anterior
      decompression followed by fusion. Average recovery rate of expansive laminoplasty
      for cervical spondylotic myelopathy has been reported to be approximately 60%
      (Japanese Orthopaedic Association score) and with long term stability. At
      present, authors consider all patients with cervical spondylotic myelopathy
      candidates for expansive laminoplasty except for those having preoperative
      kyphosis and single level lesion without canal stenosis. Two remaining problems
      of expansive laminoplasty to be solved are prevention of C5,C6 radicular pain
      and/or paresis, the most frequent complication that occurs in approximately 5% to
      10% of the patients, although most complications resolve spontaneously within 2
      years, and correction of nonlordotic alignment to lordosis which are essential
      for posterior decompression effect of expansive laminoplasty by allowing the
      spinal cord to shift dorsally.

PMID- 10078128
TI  - Diffuse idiopathic skeletal hyperostosis in the cervical spine.
AB  - The disease processes diffuse idiopathic skeletal hyperostosis, ankylosing
      spondylitis, and ossification of the posterior longitudinal ligament are similar
      in pathology and can lead to unexpected but grossly unstable fractures that may
      not be diagnosed until neurologic change occurs in cases of trivial trauma. A
      retrospective study of 29 patients with cervical spinal fractures and diffuse
      idiopathic skeletal hyperostosis-like pathologies was done. Twenty patients with
      an average age of 62 years were treated surgically (six neurologically complete,
      five incomplete, nine intact). Three patients with an average age of 70 years
      died postoperatively (one complete, two incomplete). Nine patients with an
      average age of 65 years were treated conservatively (five neurologically
      complete, two incomplete, two intact). All patients with intact neurologic
      function survived. It is suggested, therefore, that all elderly patients with
      diffuse idiopathic skeletal hyperostosis-like pathology, history of trivial
      trauma, and complaint of neck pain be examined carefully for fractures, because
      mortality rates increase sharply in patients with decreased neurologic function.

PMID- 10078129
TI  - Cervical spondylotic myelopathy. Approaches to surgical treatment.
AB  - Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction
      in older patients. This review article looks at the natural history of the
      condition and examines the role of different surgical treatments for it. Anterior
      and posterior surgical approaches have a role in the treatment of cervical
      spondylotic myelopathy dependent on the number of levels involved and the
      alignment of the spine. Anterior decompression and fusion is useful in patients
      who have disease at three or fewer levels or in patients with kyphotic alignment.
      In more extensive disease, a posterior decompression and fusion is usually best.
      Canal expansive laminoplasty is useful in the treatment of myelopathy without
      radiculopathy in a patient with lordotic alignment. With the exception of
      laminoplasty, nonfusion procedures have little role in the treatment of cervical
      spondylotic myelopathy.

PMID- 10078130
TI  - Modern alternatives and techniques for one-level discectomy and fusion.
AB  - Monosegmental cervical spondylosis with radiculopathy requiring operative
      intervention responds well to anterior disc excision and fusion with autograft.
      However, there is a 20% to 25% morbidity from the donor site. Several new
      surgical techniques using biomechanical spacers or internal fixation have been
      developed that can be used with local bone or allograft, thus eliminating donor
      site morbidity. Surgical outcomes are comparable with those of traditional
      anterior cervical discectomy and fusion.

PMID- 10078131
TI  - Transpedicle screw fixation of the cervical spine.
AB  - The use of posterior cervical spine fixation has become increasingly popular in
      recent years. Dissatisfaction with lateral mass fixation, especially at the
      cervicothoracic junction, has led spine surgeons to use cervical pedicle screw
      fixation for reconstruction in numerous cervical spine disorders. The
      biomechanical advantage of a three-column fixation device implanted to secure an
      unstable cervical spine has proven to be a valuable tool in the spine surgeon's
      armamentarium. Successful placement of a pedicle screw in the cervical spine
      requires a sufficient three-dimensional understanding of pedicle morphology to
      allow accurate identification of the ideal screw axis. Variability in cadaveric
      based morphometric measurements used to guide the surgeon in the placement of a
      pedicle screw has raised legitimate concerns as to whether transpedicle fixation
      can be applied without significant neurovascular complications. The emergence of
      computer assisted image guidance systems may be implemented in the operative
      protocol to improve the accurate placement of a pedicle screw. The indications
      for placement of a pedicle screw in the cervical spine are beginning to evolve.
      Only surgeons experienced in transpedicle screw fixation and surgery of the
      cervical spine should perform this method of instrumentation.

PMID- 10078132
TI  - Metastatic disease of the cervical spine. A review.
AB  - The treatment of cervical metastatic disease requires a multidisciplinary team
      approach to evaluation and management and demands consideration of multiple
      factors before a regimen is accepted. The patient's overall functioning and
      medical status, life expectancy, history of treatment, tumor type, and location
      within the cervical spine and individual vertebrae all must be evaluated
      carefully. The majority of lesions will be amenable to nonoperative aggressive
      modalities aimed at shrinking tumor size and halting growth. Surgical
      intervention is limited to specific indications, including spinal instability,
      progressive neurologic deterioration from bony collapse and compression,
      intractable pain, and failure of conservative means of treatment.

PMID- 10078133
TI  - Early versus delayed surgery for acute cervical spinal cord injury.
AB  - The optimal timing of surgical intervention in cervical spinal cord injuries has
      not been defined. The goals of the study were to investigate changes in
      neurologic status, length of hospitalization, and acute complications associated
      with surgery within 3 days of injury versus surgery more than 3 days after the
      injury. All patients undergoing surgical treatment for an acute cervical spinal
      injury with neurologic deficit at two institutions between March 1989 and May
      1991 were reviewed retrospectively. Forty-three patients initially were
      evaluated. At one institution, patients with neurologic spinal injuries had
      surgical intervention within 72 hours of injury. At the other institution,
      patients underwent immediate closed reduction with subsequent observation of
      neurologic status for 10 to 14 days before undergoing surgical stabilization.
      This study indicates that patients who sustain acute traumatic injuries of the
      cervical spine with associated neurologic deficit may benefit from surgical
      decompression and stabilization within 72 hours of injury. Surgery within 72
      hours of injury in patients sustaining acute cervical spinal injuries with
      neurologic involvement is not associated with a higher complication rate. Early
      surgery may improve neurologic recovery and decrease hospitalization time in
      patients with cervical spinal cord injuries.

PMID- 10078134
TI  - Transmaxillary anterior decompressions in patients with severe basilar
      impression.
AB  - Severe basilar impression leads to an upward translocation of the upper cervical
      spine and clivus into the foramen magnum and is a diagnosis best made with
      computed tomography or magnetic resonance imaging scans. Basilar impression may
      be a primary condition or secondary to bone softening disorders. Symptoms
      relating to direct neuraxial compression, obstruction to cerebral spinal fluid
      outflow, and vascular compromise all have been described. Management depends on
      the exact nature of the abnormality seen, but it is now firmly accepted that
      those with anterior neuraxial compression should have an anterior decompression.
      The severe basilar impression and craniofacial abnormalities seen in osteogenesis
      imperfecta together with the progressive nature of the condition have led to the
      development of a specific surgical response, the open door maxillotomy combined
      with a contoured loop fixation of the cervical spine. Little is known of the long
      term outcome of severe basilar impression, and long term studies undertaken by
      centers familiar with the condition and its management are required if definitive
      care is to be delivered to these patients.

PMID- 10078135
TI  - Modified Gallie technique versus transarticular screw fixation in C1-C2 fusion.
AB  - The effectiveness of a modified Gallie technique versus Magerl and Seeman
      transarticular screw fixation was compared in the management of 27 patients with
      symptomatic atlantoaxial instability. Twelve patients were treated using a
      modified Gallie technique and postoperative halo vest immobilization.
      Atlantoaxial arthrodesis occurred in seven (58%) patients, stable fibrous union
      occurred in one patient, and pseudarthrosis with recurrent instability developed
      in four (33%) patients. Average followup was 6.9 years. All 15 patients treated
      using Magerl and Seeman transarticular screw fixation and postoperative soft
      collar immobilization had atlantoaxial arthrodesis develop. Average duration of
      followup was 4 years. One patient sustained vertebral artery injury during
      preparation for screw placement. Magerl and Seeman transarticular screw fixation
      provides stability and more reliably produces atlantoaxial arthrodesis than the
      Gallie technique provides in patients with atlantoaxial instability without the
      need for rigid postoperative bracing. Potential for vertebral artery exists
      despite apparent accurate screw placement. To ensure that safe transarticular
      screw placement is possible, preoperative fine cut axial computed tomography with
      reconstructions is required to assess vertebral artery position and C2 isthmus
      anatomy. A proportion of patients have anatomy unsuitable for screw placement.
      Traditional wiring techniques are indicated in these patients.

PMID- 10078136
TI  - Functional outcome of plate fusions for disorders of the occipitocervical
      junction.
AB  - Twenty-eight patients with average followup of 27 months (range, 12-51 months)
      required occipitocervical fusion with plates. A 1992 to 1996 consecutive case
      series enrolled patients prospectively from two institutions. Five surgeons
      participated. Sixteen patients had inflammatory arthritis; four, osteogenesis
      imperfecta; three, tumors; three, congenital anomalies; one, pseudarthrosis after
      odontoid fracture; and one, osteoarthritis. Twenty-two of 28 (78.6%) patients had
      serious comorbid medical conditions. Additional halo immobilization of 6 weeks
      was used in 16 of 27 patients. Four patients required revision surgery. No
      patients showed a decline in neurologic status and average neurologic improvement
      was one Nurick grade. Two-year followup showed 13 (50%) excellent, nine (34.6%)
      good, two (7.7%) fair, and two (7.7%) poor outcomes based on a functional outcome
      scale. There were three deaths during the followup period (overall mortality rate
      of 10.7%). One death was attributable to airway obstruction, one death 14 months
      postoperatively was attributable to late Methicillin resistant Staphylococcus
      aureus sepsis at the bone graft donor site, and one death 41 months
      postoperatively was attributable to a stroke. The overall fusion rate was 85.2%
      (23 of 27 patients), with a 96.3% (26 of 27 patients) occipitocervical fusion
      rate. Three patients had a possible asymptomatic end segment pseudarthrosis with
      screw loosening. Twenty-two of 26 (84.6%) interviewed patients would choose the
      surgery again if given the choice.

PMID- 10078137
TI  - Panclavicular ankylosis in pustulotic arthroosteitis. A case report.
AB  - A 54-year-old man who had palmoplantar pustulosis showed bilateral, complete
      osseous fusion of the sternoclavicular and acromioclavicular joints. No
      significant abnormality was seen in the glenohumeral joint. The left clavicle had
      a nonunion develop, whereas the right did not. The elevation of the right
      shoulder was limited to 100 degrees in active and passive measurements. The total
      external rotation and internal rotation at the side was 135 degrees. This
      decreased to 90 degrees at 60 degrees elevation and to 10 degrees at maximum (100
      degrees) elevation. Based on the kinematic data on normal shoulders, it was
      thought that the ankylosis of both ends of the clavicle held the scapula
      unrotated during the arm movement so that, at the arm to trunk angle of 100
      degrees, the position of the humerus relative to the scapula was equivalent to
      that of a normal shoulder in complete elevation. The current case provided an
      extremely rare clinical setting where shoulder mobility depended only on
      glenohumeral motion as a result of the complete loss of scapulothoracic motion.

PMID- 10078138
TI  - A technique for reconstruction of the medial patellofemoral ligament.
AB  - Additional medial patellofemoral ligament reconstruction was performed
      successfully on six consecutive patients with recurrent dislocation of the
      patella because of residual patellar instability after medial transfer of the
      tibial tubercle. A technique for medial patellofemoral ligament reconstruction is
      described, and complications and postoperative management are discussed. The
      reconstruction was performed using a double strand hamstring tendon graft in five
      patients and iliotibial allograft in one. Good stabilization of the patella was
      achieved in all six patients, resulting in improved confidence in higher levels
      of activity. The satisfactory outcome of additional medial patellofemoral
      ligament reconstruction suggests the possibility that the procedure may be part
      of the optional procedure in proximal realignment for recurrent dislocation of
      the patella.

PMID- 10078139
TI  - Arthroscopic posterior cruciate ligament reconstruction using a one-incision
      technique.
AB  - Thirty-seven patients with a posterior cruciate ligament injury underwent
      arthroscopic posterior cruciate ligament reconstruction using a one-incision
      technique with bone-patellar tendon-bone autograft or allograft. The tibial
      tunnel was started at the distal end of the graft donor site on the proximal
      tibia and exited posteriorly at the flat spot 15 mm below the articular margin
      and just lateral to the midline. The femoral tunnel was made through the lateral
      anterolateral portal. The 25 mm long proximal bone plug was passed easily through
      the tibial tunnel using a specially designed suture pusher and guided into the
      femoral tunnel by pulling the leading suture with the knee flexed 30 degrees.
      Firm proximal and distal fixations were achieved with interference screws. At a
      minimum 2 year followup (range, 24-68 months), average knee ligament evaluation
      scores were 91.1 (range, 67-99) in the Lysholm knee scoring scale and 89.3
      (range, 67-99) in the Hospital for Special Surgery knee ligament rating form. The
      average side to side difference of the posterior translation measured by the KT
      2000 arthrometer was 6.08 (range, 5-7 mm) mm preoperatively and 2.2 (range, 0-6
      mm) mm postoperatively. There were no significant differences between the acute
      and the chronic cases. The results of the isolated posterior cruciate ligament
      injury group were better than the combined ligamentous injury group. The one
      incision technique minimizes injury to the extensor mechanism, especially the
      vastus medialis obliquus muscle, and medial scar. Rigid fixation of the long
      proximal bone plug allows early rehabilitation.

PMID- 10078140
TI  - Polyethylene particle morphology in synovial fluid of failed knee arthroplasty.
AB  - Synovial fluid from the knees of 16 patients undergoing revision knee
      arthroplasty for aseptic failure was subjected to base digestion and
      ultrafiltration. Filtered particles were scanned using scanning electron
      microscopy and analyzed with an image program. Polyethylene particles were
      identified visually and confirmed with the use of electron diffraction
      spectroscopy. Averaging more than 1500 particles per patient sample, 25,148
      particles were analyzed. This corresponded to a concentration of 3000
      polyethylene particles per milliliter of synovial fluid. Three populations of
      wear debris were identified in the fluid. Small globular particles with a mean
      area of 75 mu 2 represented 94% of all particles observed. The particles averaged
      10 mu in diameter and often were seen in clumps. Long fibrous particles with a
      mean area of 1164 mu 2 made up 4% of the particle population. Large rhomboidal
      particles with an area of 557 mu 2 were observed least commonly and comprised the
      remainder of the particles visualized. All three particle types were observed in
      each fluid sample regardless of the wear pattern of the retrieved polyethylene
      liner. There were no differences in absolute particle counts, particle
      morphologic characteristics, or particle size between patients with and without
      gross polyethylene wear.

PMID- 10078141
TI  - Cryosurgery in the treatment of giant cell tumor. A long-term followup study.
AB  - Between 1983 and 1993, 102 patients with giant cell tumor of bone were treated at
      three institutions. Sixteen patients (15.9%) presented with already having had
      local recurrence. All patients were treated with thorough curettage of the tumor,
      burr drilling of the tumor inner walls, and cryotherapy by direct pour technique
      using liquid nitrogen. The average followup was 6.5 years (range, 4-15 years).
      The rate of local recurrence in the 86 patients treated primarily with
      cryosurgery was 2.3% (two patients), and the overall recurrence rate was 7.9%
      (eight patients). Six of these patients were cured by cryosurgery and two
      underwent resection. Overall, 100 of 102 patients were cured with cryosurgery.
      Complications associated with cryosurgery included six (5.9%) pathologic
      fractures, three (2.9%) cases of partial skin necrosis, and two (1.9%)
      significant degenerative changes. Overall function was good to excellent in 94
      patients (92.2%), moderate in seven patients (6.9%), and poor in one patient
      (0.9%). Cryosurgery has the advantages of joint preservation, excellent
      functional outcome, and low recurrence rate when compared with other joint
      preservation procedures. For these reasons, it is recommended as an adjuvant to
      curettage for most giant cell tumors of bone.

PMID- 10078142
TI  - Vascularized fibular graft after excision of giant cell tumor of the distal
      radius. A case report.
AB  - Although hemiarthroplasty of the wrist using vascularized proximal fibula has
      been described often, long term results with documentation of results are
      insufficient. A case of giant cell tumor of the distal radius with remarkable
      extraskeletal extension is reported. Vascularized fibula including its proximal
      head was used to replace the defect created after en bloc resection of the tumor.
      There was no deterioration in radiographic findings or function of the new joint
      at the time of the 10-year followup. Satisfactory range of motion of the wrist
      and the forearm was maintained. There was no instability in the joint, and grip
      strength measured 65% of the opposite side. Postoperative magnetic resonance
      imaging showed survival of the whole graft, including the subchondral portion. In
      addition to thorough revascularization of the graft, appropriate soft tissue
      reconstruction using dynamic tendon transfer contributed to the success. When
      these requirements are fulfilled, the graft can provide a functional and durable
      result. Although this is a single experience, the authors recommend wrist
      arthroplasty, rather than arthrodesis, in carefully selected patients.

PMID- 10078143
TI  - Alveolar soft part sarcoma involving the ilium. A case report.
AB  - A report of alveolar soft part sarcoma of the hip region with extension to the
      ilium is presented to highlight an unusual presentation for this sarcoma and to
      discuss the treatment options for limb salvage for large malignant neoplasma
      involving the periacetabular region of the pelvis. A review of the literature for
      reports of alveolar soft part sarcoma extending to bone is presented.

PMID- 10078144
TI  - Salvage of contaminated fractures of the distal humerus with thin wire external
      fixation.
AB  - Fractures and osteotomies of the distal humerus that are contaminated or infected
      represent a difficult management problem. Stable anatomic fixation with plates
      and screws, the acknowledged key to a good result in the treatment of bicondylar
      fractures, may be unwise. A thin wire circular (Ilizarov) external fixator was
      used as salvage treatment in such complex situations in five patients. The
      fixator allowed functional mobilization of the elbow while allowing achievement
      of the primary goal of eradicating the infection or colonization. Two patients
      required a second operation for fixation of a fibrous union of the lateral
      condyle. One patient with a vascularized fibular graft later required triple
      plate fixation for malalignment at the distal host and graft junction. Four of
      five patients ultimately achieved complete union. The fracture remained ununited
      in one patient who has declined additional intervention. All five patients
      achieved at least 85 degrees ulnohumeral motion, two after a secondary elbow
      capsulectomy performed after healing was achieved. This experience suggested that
      the Ilizarov construct, although not a panacea, represents a reliable method of
      skeletal stabilization that allows functional mobilization while elimination of
      infection or colonization is ensured. If necessary, stiffness and incomplete
      healing can be addressed with an increased margin of safety at subsequent
      operations.

PMID- 10078145
TI  - Dislocation of the first metatarsophalangeal joint with fracture of fibular
      sesamoid. A case report.
AB  - Dorsal dislocations of the first metatarsophalangeal joint are classified by
      Jahss into two types. In Type 1, the hallux with the intact intersesamoid
      ligament dislocates dorsally over the metatarsal head. Such cases in the
      literature have been irreducible by closed manipulation. In Type 2 the hallux is
      dislocated dorsally with rupture of the intersesamoid ligament, resulting in wide
      separation of the sesamoids (Type 2A) or a transverse fracture of one or both
      sesamoids (Type 2B). The importance in classifying these injuries allows one to
      predict whether closed reduction will be successful as in Type 2. The patient
      reported had a fracture of the fibular sesamoid in addition to dislocation of the
      hallux. The clinical findings were consistent with Type 1 injury, including an
      intact intersesamoid ligament, but the radiographs showed, in addition to the
      dislocation, that there was a fracture of the fibular sesamoid. Reduction was
      achieved surgically through a dorsal approach. Although such injuries have been
      unreported previously, Type 1 injuries may be associated with a fracture of the
      fibular sesamoid but without rupture of intersesamoid ligament, so the injury
      reported is classified as Type 1A.

PMID- 10078146
TI  - Effects of tourniquet compression on neuromuscular function.
AB  - Neuromuscular function in New Zealand White rabbits was evaluated after thigh
      tourniquet compression in the directly compressed quadriceps muscles and the
      distal tibialis anterior by measuring isometric contractile function after
      supramaximal stimulation of the motor nerve. Tourniquet compression resulted in
      markedly decreased force production beneath and distal to the tourniquet. Two
      days after compression, maximal quadriceps force production was decreased to 46%
      of control values with 125 mm Hg compression and 21% of control values after 350
      mm Hg compression. Maximum tibialis anterior force production declined to 70% of
      control values after 125 mm Hg thigh compression and 24% of control values after
      350 mm Hg thigh compression. Functional deficits were greater in the directly
      compressed quadriceps muscles, but the quadriceps and tibialis anterior had
      significantly increased impairment when the tourniquet inflation pressure was
      increased from 125 mm Hg to 350 mm Hg. Three weeks after compression, quadriceps
      function had returned to 94% of control value after 125 mm Hg compression and 83%
      after 350 mm Hg. Tibialis anterior function returned to 88% of control values
      after 125 mm Hg thigh compression and 83% after 350 mm Hg. Clinically, the use of
      lower inflation pressures may minimize the complications of tourniquet use and
      enhance postoperative recovery.

PMID- 10078147
TI  - The effects of tensile load on the metabolism of cultured chondrocytes.
AB  - The effect of cyclic tensile load on articular cartilage metabolism was
      investigated experimentally using 12 Japanese White rabbits. Chondrocytes
      obtained from the knee joints were cultured on plates with flexible silicone
      rubber bases. They were subjected to a cyclic (3 seconds on and 3 seconds off)
      tensile load for 24 hours with a maximum increase in area of 17%. Proteoglycan
      synthesis, collagen synthesis, and tissue inhibitors of metalloproteinases
      production by the chondrocytes under the load were quantified and compared with
      those produced by the control cells in an unloaded condition. The cultured
      chondrocytes under the cyclic tensile load perpendicularly aligned to the
      direction of the tensile load. Collagen synthesis and tissue inhibitors of
      metalloproteinases production increased significantly under the cyclic tensile
      load, although no significant change in proteoglycan synthesis was observed.
      These results suggested that the cyclic tensile load on the chondrocytes
      contribute to the regulation of articular cartilage metabolism in part.

PMID- 10078148
TI  - Oral rifampin plus azithromycin or clarithromycin to treat osteomyelitis in
      rabbits.
AB  - A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day
      combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus
      oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice
      daily), or parenteral nafcillin (30 mg/kg, four times daily). The left tibial
      metaphysis of New Zealand White rabbits was infected with Staphylococcus aureus.
      Grades 3 to 4 osteomyelitis (according to the Cierny-Mader classification system)
      development in the rabbits was confirmed radiographically. After antibiotic
      therapy regimens of 28 days, all tibias from controls that were infected but left
      untreated (n = 10) revealed positive cultures for Staphylococcus aureus at a mean
      concentration of 2.8 x 10(4) colony forming units/g bone. The rifampin plus
      clarithromycin (n = 15) and rifampin plus azithromycin (n = 15) groups showed
      significantly lower percentages of positive Staphylococcus aureus infection (20%
      and 13.3%, respectively) and bacterial concentrations (3.5 x 10(1) and 1.75 x
      10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the
      nafcillin plus rifampin treated group (n = 7) showed no detectable Staphylococcus
      aureus infection (significantly lower than controls). The differences observed
      for bone bacterial concentrations and sterilization percentages between the
      antibiotic treated groups were not statistically significant. Although
      fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents usually
      prescribed with rifampin, increasing resistance has been observed. Although
      macrolides traditionally are not used in the treatment of osteomyelitis, the
      results of this study indicate that azithromycin and clarithromycin may be
      attractive partners for rifampin for the treatment of Staphylococcus aureus
      osteomyelitis in humans.

PMID- 10078149
TI  - Anatomy of the scapulothoracic articulation.
AB  - Four fresh frozen human cadavers (eight extremities) consisting of the head,
      neck, thorax, and entire upper extremities were used for dissection of the
      scapulothoracic articulation. In each specimen, the spinal accessory nerve, all
      relevant muscle insertions, and bursae were identified and measured. The
      structures of the scapulothoracic articulation can be divided into superficial,
      intermediate, and deep layers. The superficial layer consists of the trapezius,
      latissimus dorsi, and an inconsistent bursa between the inferior angle of the
      scapula and the latissimus dorsi. The intermediate layer consists of the levator
      scapulae, rhomboid minor and major, spinal accessory nerve, and scapulotrapezial
      bursa located between the superomedial scapula and the overlying trapezius. In
      all specimens, the spinal accessory nerve traveled intimately along the wall of
      the scapulotrapezial bursa, an average of 2.7 cm lateral to the superomedial
      angle of the scapula. The deep layer consists of the serratus anterior,
      subscapularis, and two bursae: one between the serratus and the thorax, the
      scapulothoracic bursa; and one between the subscapularis and the serratus, the
      subscapularis bursa.

PMID- 10078150
TI  - Publication rates of abstracts presented at the 1993 annual Academy meeting.
AB  - What percent of abstracts presented at the American Academy of Orthopaedic
      Surgeons annual meeting are submitted, survive peer review, and eventually are
      published? The answer to this fundamental question is important because many
      national meeting attendees use the unscrutinized information that is presented to
      alter their surgical practices. At the 1993 American Academy of Orthopaedic
      Surgeons meeting, 573 abstracts were presented. After a 5-year period, 44% of
      abstracts presented were published as papers in a peer reviewed journal. The
      results suggest that for various reasons, the majority of presented material at
      the Academy meeting has not been authenticated scientifically to be as accurate
      as papers that survive the rigors of peer review.

PMID- 10078151
TI  - Distal thigh pain in a 14-year-old girl.

PMID- 10078152
TI  - The compares a unipolar with a bipolar prosthesis of similar stem design.

PMID- 10078153
TI  - Concentrations in human fluids: 101 drugs affecting the digestive system and
      metabolism.
AB  - BACKGROUND: The toxicological interpretation of blood and urine concentrations of
      drugs affecting the digestive system and metabolism, as with other groups of
      pharmaceutical specialties, is complicated. METHODS: As a continuation of our
      published studies on the concentrations of drugs of abuse, drugs affecting
      cardiovascular and hematopoietic systems, and respiratory system, we have
      reviewed the published data relating to the concentrations of drugs affecting the
      digestive system and metabolism in clinical and forensic cases. We have selected
      them on the basis of conservative criteria and our own experience. RESULTS: A
      table with concentrations of 101 drugs in whole blood, serum/plasma, and urine,
      corresponding to therapeutic, toxic, or lethal concentrations, is presented.
      CONCLUSIONS: The data can help interpret analytical results of patient or
      postmortem samples when there is a suspicion of poisoning with this group of
      drugs.

PMID- 10078154
TI  - Aspiration of activated charcoal elicits an increase in lung microvascular
      permeability.
AB  - BACKGROUND: Gastric decontamination with orally administered activated charcoal
      is the recommended treatment for many poisonings. However, ingestion of central
      nervous system depressants resulting in loss of protective airway reflexes may
      result in pulmonary aspiration of activated charcoal. Although activated charcoal
      has been reported to be an inert substance, evidence suggests that pulmonary
      aspiration of charcoal is associated with lung edema formation and pulmonary
      compromise. This study tested the hypothesis that intratracheal instillation of
      activated charcoal disrupts the integrity of the lung microvascular barrier.
      METHODS: The capillary filtration coefficient (Kf,c), a sensitive measure of lung
      microvascular permeability, was determined isogravimetrically prior to and after
      intratracheal instillation of activated charcoal 0.04 g/kg (12% weight/vol
      solution, pH 7.4) or an equal volume of sterile water in isolated, perfused rat
      lungs. Arterial blood gas analysis was determined prior to and after tracheal
      instillation of activated charcoal or sterile water in a separate group of
      animals. RESULTS: Intratracheal instillation of activated charcoal resulted in a
      significant increase in pulmonary microvascular permeability compared to lungs
      treated with sterile water or control lungs (delta Kf,c = +0.21 +/- 0.076; -0.014
      +/- 0.04; and -0.041 +/- 0.02 mL/min/cm H2O/100 g lung tissue, respectively, p <
      0.05 ANOVA). There was no significant difference in baseline blood gases in the 3
      experimental groups. There was a significant decrease in arterial Po2,
      bicarbonate, and pH in animals administered activated charcoal compared to time
      matched controls and animals administered sterile water. CONCLUSIONS:
      Intratracheal instillation of activated charcoal is associated with a significant
      increase in lung microvascular permeability and arterial blood gas derangements.
      The effects of activated charcoal on pulmonary microvascular barrier integrity
      may contribute to the lung edema formation and pulmonary compromise observed
      following clinical aspiration of activated charcoal.

PMID- 10078155
TI  - Activated charcoal--treatment or toxin?

PMID- 10078156
TI  - Iron-mediated cardiotoxicity develops independently of extracellular hydroxyl
      radicals in isolated rat hearts.
AB  - BACKGROUND: Myocardial iron toxicity is often attributed to free radical damage.
      Present studies examine the role of extracellular hydroxyl radical formation in
      this process. METHODS: In vitro reactions examined the rate of hydroxyl radical
      formation using salicylate trapping with high-pressure liquid chromatography
      separation and electrochemical detection of 2,3- and 2,5- dihydroxybenzoic acid.
      Isolated rat hearts were perfused by the Langendorff technique under the same
      buffer conditions to determine changes in myocardial contractility, release of
      tissue lactate dehydrogenase activity, and formation of lipid peroxidation
      products when iron was added to the perfusate with or without the formation of
      extracellular radicals. RESULTS: In vitro reactions, performed in Krebs buffer
      alone or with addition of iron (25 microM), produced levels of hydroxyl radicals
      that were nondetectable with salicylate trapping. Addition of iron/ascorbate
      (FeSO4 = 25 microM, ascorbate = 1 mM), or iron/ascorbate/histidine (FeSO4 = 25
      microM, ascorbate = 1 mM, histidine = 15 mM) produced significant and equivalent
      accumulation of hydroxyl radicals. Isolated rat hearts were perfused under the
      same 4 conditions. Control heart contractile function was stable with little
      release of lactate dehydrogenase activity and low levels of thiobarbituric acid
      reactive substances (TBARS). There was significant and equal injury to
      contractile function, release of lactate dehydrogenase activity, and accumulation
      of TBARS in hearts in the presence (iron/ascorbate) and absence (iron alone) of
      extracellular hydroxyl radicals. In addition, there was significant reduction in
      injury with iron/ascorbate/histidine, where the formation of extracellular
      hydroxyl radicals was equal to those observed with iron/ascorbate alone.
      Additional control hearts, perfused with histidine alone, showed stable heart
      function. CONCLUSIONS: These findings indicate that the extracellular formation
      of hydroxyl radicals is not responsible for iron-mediated cardiotoxicity.

PMID- 10078157
TI  - Experimental treatment of the acute cardiovascular toxicity of caffeine.
AB  - STUDY DESIGN: The intravenous infusion of caffeine-sodium salicylate (15
      mg/kg/min) into artificially ventilated and anesthetized rats caused a
      progressive fall in arterial blood pressure which was mainly due to a decrease in
      peripheral resistance. Cardiac output increased initially by 15% but then
      declined after 30 minutes. The electroencephalogram showed sinus tachycardia and
      ectopic beats mainly in the form of monomorphic ventricular bigeminy which began
      after 22.8 minutes. Fatal ventricular fibrillation occurred in all animals by
      66.9 +/- 3.1 minutes. Treatment of cardiac arrhythmia by repeated intravenous
      injections of propranolol (1 mg/kg) or verapamil (1 mg/kg) was effective and
      prolonged survival time to 91.7 +/- 4.4 or 84.3 +/- 2.9 minutes, respectively (p
      < 0.05). Propranolol also prolonged survival time when administered in a single
      dose of 20 mg/kg i.v. 10 minutes before the initiation of caffeine infusions.
      Repeated administrations of quinidine sulfate (5 mg/kg), phenytoin (5 mg/kg), or
      lidocaine (1-5 mg/kg), on the other hand, exerted very short antiarrhythmic
      activity and did not prolong survival time at all. Fluid therapy with polygeline
      plasma expander (0.5 mL/kg/min) did not influence caffeine-induced cardiovascular
      failure in any way. CONCLUSIONS: Ventricular ectopia leading to fibrillation
      accounts for the lethal outcome of caffeine poisoning in anesthetized rats and
      can be antagonized by treatment with propranolol or verapamil.

PMID- 10078158
TI  - Effect of metoclopramide dose on preventing emesis after oral administration of N
      acetylcysteine for acetaminophen overdose.
AB  - OBJECTIVE: To determine the effect of the metoclopramide dose on the prevention
      of vomiting of N-acetylcysteine in acetaminophen overdose. METHODS: Patients with
      acetaminophen ingestions receiving metoclopramide prior to emergency department
      administration of N-acetylcysteine were included. Emergency Department and poison
      center records were reviewed for administration of metoclopramide pre-N
      acetylcysteine and incidence of subsequent vomiting. The treatment group was
      defined as patients receiving high-dose metoclopramide (20-50 mg intravenously)
      prior to the loading dose of N-acetylcysteine. Controls were patients receiving
      standard-dose (< 20 mg intravenously) metoclopramide prior to loading dose of N
      acetylcysteine. Outcome was vomiting within 60 minutes of N-acetylcysteine
      administration. RESULTS: Twelve of 19 patients (63%) receiving standard-dose
      metoclopramide vomited N-acetylcysteine. Only 5 of 23 patients (22%) receiving
      high-dose metoclopramide vomited N-acetylcysteine (crude odds ratio: 6.2; 95% CI
      [1.3-30.3]). After controlling for confounding in the logistic regression model,
      the effect of high-dose metoclopramide in preventing vomiting of N-acetylcysteine
      remained significant (adjusted odds ratio: 17.0; 95% CI [2.6-110.0]). CONCLUSION:
      This study supports the efficacy of high-dose metoclopramide to prevent emesis
      after the oral loading dose of N-acetylcysteine.

PMID- 10078159
TI  - Opiate detoxification under anesthesia: no apparent benefit but suppression of
      thyroid hormones and risk of pulmonary and renal failure.
AB  - INTRODUCTION: The new technique for opiate detoxification using anesthesia and
      high, repetitive doses of opiate-antagonists claims to detoxify addicts without
      withdrawal symptoms within 24-48 hours. We studied the method with 12 opiate
      addicts (5 L-polamidone, 4 dihydrocodeine, 3 heroin), using general anesthesia
      and the antagonists naloxone 0.5 mg/kg and naltrexone > 150 mg. Objective and
      subjective withdrawal symptoms were measured until urine was free of drugs and
      patients had no withdrawal symptoms. Thyroid hormones were measured before,
      during, and after the anesthesia period. RESULTS: All patients had moderate to
      severe opiate withdrawal symptoms. No detoxification was finished within 48
      hours. The dihydrocodeine subjects were compared with conventionally detoxified
      controls; no difference was seen. The method suppressed thyroid hormones TT3,
      TT4, and TSH. The study was terminated because of side effects: 1 pulmonary
      failure and 2 renal failures. All patients survived without sequelae. CONCLUSION:
      There is no obvious benefit from this method, whereas the risks are high.

PMID- 10078160
TI  - Efficacy of serotherapy in scorpion sting: a matched-pair study.
AB  - BACKGROUND/OBJECTIVE: Although evidence of scorpion antivenin effectiveness in
      the clinical setting is lacking, scorpion antivenin is generally considered the
      only specific treatment for scorpion sting irrespective of its clinical severity.
      We conducted a matched-pair study to assess the efficacy of systematic
      administration of scorpion antivenin. METHODS: Among 600 stung patients who
      participated in a study on the efficacy of high-dose hydrocortisone after
      scorpion sting, 135 (cases) had been treated with 10 to 20 mL intravenous
      scorpion antivenin (neutralizing 10 LD50 venom/mL). Controls were matched on
      disease severity on arrival to the emergency department. The severity of
      envenomation was graded I or II according to the absence (grade I) or the
      presence (grade II) of systemic manifestations of scorpion envenomation.
      Assessment of scorpion antivenin efficacy was based on the rate of changing
      severity grade in both groups (clinical improvement or worsening during an
      observation period of at least 4 hours). RESULTS: Both groups were similar with
      respect to clinical severity (36 patients were graded II in each group), age,
      sex, time-lapse between scorpion sting and ED arrival, and the administration of
      adjunctive therapy such as hydrocortisone. By the 4-hour evaluation, 50% and 64%
      of patients initially graded II exhibited a substantial clinical improvement in
      cases and controls, respectively, suggesting similar effects in cases and
      controls. There was no difference in preventive effects: 13% and 10% of cases and
      controls developed systemic manifestations of scorpion envenomation during the 4
      hour observation period; 23% of cases and 17% controls were hospitalized by this
      time. There was no difference in the duration of hospitalization. Three cases
      developed anaphylactic shock as a consequence of scorpion antivenin
      administration, while 1 scorpion antivenin-untreated patient died from refractory
      shock. CONCLUSION: Systematic administration of scorpion antivenin irrespective
      of clinical severity did not alter the clinical course of scorpion sting. A
      prospective study is needed concerning the response of the more severe scorpion
      envenomations.

PMID- 10078161
TI  - A placebo-controlled experimental study of steroid inhalation therapy in ammonia
      induced lung injury.
AB  - BACKGROUND: The use of corticosteroids in toxic lung injury caused by exposure to
      an irritating gas such as ammonia has not been adequately studied. OBJECTIVE: To
      evaluate the effects of budesonide inhalation in a rabbit model of toxic lung
      injury induced by ammonia. DESIGN: Randomized, blind placebo-controlled
      laboratory investigation employing 16 New Zealand White rabbits. Lung injury was
      induced by inhalation of a defined amount of aerosolized ammonia. Thirty minutes
      later, the rabbits were randomized to receive either inhalation therapy with 0.5
      mg budesonide or placebo. After another 2 hours, a second treatment inhalation,
      identical to the first one, was administered. RESULTS: Airway pressures,
      hemodynamics, and gas exchange were measured at baseline, 5, and 15 minutes after
      ammonia administration and every 30 minutes during a 6-hour period after the
      first blind inhalation of corticosteroids or placebo. The ammonia inhalation
      resulted in an acute severe lung injury, detected after 15 minutes as a decrease
      in Pao2 from 23.3 (+/- 3.6) to 11.0 (+/- 3.6) kPa (p < 0.005) and an increase in
      peak airway pressure from 13 (+/- 2) to 17 (+/- 2) cm H2O (p < 0.005). During the
      6-hour observation period, the blood gas parameters improved gradually in all
      rabbits. In comparison with placebo, budesonide did not result in improved gas
      exchange or reduced airway pressure levels during the observation period.
      CONCLUSION: In this animal model corticosteroid inhalation therapy had no effect
      on ammonia-induced lung injury.

PMID- 10078162
TI  - Methanol-related deaths in Ontario.
AB  - OBJECTIVE: Methanol poisoning accounts for several deaths annually in the
      province of Ontario. Our study was aimed at identifying the associated
      epidemiological factors for fatal outcomes following methanol poisoning in order
      to develop preventative strategies. METHODS: The records of the Ontario
      Provincial Coroner's Office were reviewed retrospectively for all poison-related,
      alcohol-related, and chronic alcohol use-related deaths for the period of January
      1, 1986 to December 31, 1991. Age, gender, reason for ingestion (accidental or
      intentional), and source of methanol for each victim were recorded. RESULTS:
      There were 43 fatalities during this period, 39 males and 4 females with a mean
      age of 45 years (range 18-80). Suicide attempts accounted for 21 (49%) cases
      while the remaining 22 (51%) deaths were classified as accidental. Fourteen (64%)
      of these 22 patients consumed products labeled as methyl alcohol or wood alcohol
      as a substitute for ethanol. In 3 cases, the accidental ingestion was the direct
      result of methanol being improperly stored in containers normally associated with
      ethanol. The remaining 5 patients were poisoned through the consumption of liquor
      from illicit sources. CONCLUSIONS: Over half of the methanol-related deaths in
      Ontario are accidental and potentially preventable. Possible preventative
      strategies include mandatory product relabeling to eliminate the word alcohol,
      enhanced public education, and the addition of aversive agents to methanol
      containing commercial products.

PMID- 10078163
TI  - Accuracy of an enzymatic assay device for serum ethanol measurement.
AB  - OBJECTIVE: To determine the accuracy of an enzymatic assay of serum to measure
      blood ethanol levels in the emergency department. METHODS: A blinded, prospective
      study of emergency department patients for whom a blood ethanol was ordered and
      performed. After skin prep with betadine, two blood samples were drawn into
      separate sodium fluoride-containing vacutainers. One sample was sent to the
      hospital laboratory for blood ethanol analysis. The other was centrifuged for 5
      minutes and the serum was then assayed using the QED A350 Saliva Alcohol Test.
      Values were then compared by kappa statistic and Pearson's correlation.
      Sensitivity and specificity calculations were determined for the QED device to
      detect a blood ethanol > 100 mg/dL. RESULTS: Sixty-six patients were enrolled.
      The kappa value for QED compared to lab blood ethanol was 0.93. The Pearson's
      correlation coefficient was 0.94. The QED, in general, tended to overestimate
      blood ethanol slightly. The QED was 100% sensitive and 82% specific in detecting
      a blood ethanol > 100 mg/dL. CONCLUSIONS: Analysis of serum using a QED A350' is
      a sensitive and accurate index of low to moderate increases in blood ethanol
      appropriate to emergency department, but not legal, interpretation.

PMID- 10078164
TI  - Acute poisoning with a herbicide containing imazapyr (Arsenal): a report of six
      cases.
AB  - BACKGROUND: Acute pesticide poisoning is a major cause of morbidity and mortality
      in Taiwan and herbicides are most frequently implicated. Imazapyr [2-(4-isopropyl
      4-methyl-5-oxo-2 imidazoline-2-yl)nicotinic acid] is a new herbicide, recently
      registered in Taiwan under the tradename "Arsenal" (Imazapyr 23.1%, Cyanamid
      Taiwan Corporation, Taipei). Imazapyr is also marketed as Assault, Chopper,
      Contain, and Pivot. To the best of our knowledge, there is no information in the
      literature concerning acute toxicity in humans after ingestion of herbicides
      containing this compound. METHOD: Six cases of acute poisoning with Arsenal
      occurred during the period 1993-1997 in a single hospital. Emergency room records
      and medical charts were reviewed. RESULTS: Of 6 cases, 5 were suicide attempts
      and 1 was an act of violence inflicted on a child. Three of the 6 patients (50%)
      presented with severe symptoms, including impairment of consciousness and
      respiratory distress requiring intubation. Other presentations included metabolic
      acidosis (2), hypotension (2), leukocytosis (3), fever (2), mild elevation of
      hepatic transaminase and creatinine (2), unconjugated hyperbilirubinemia (2),
      oral ulceration (2), pharyngolaryngitis (2), and chemical burns of the cornea
      (1). All cases had copious vomiting after ingestion of Arsenal. No mortality
      occurred. CONCLUSION: According to our observations, it appeared the toxic
      syndrome that results from a large quantity (> 100 mL) of Arsenal herbicide
      ingestion consists of hypotension, pulmonary dysfunction, oral mucosal and
      gastrointestinal irritation, and transient liver and renal dysfunction. However,
      the existence of a dose-response relationship, with increasing amounts of
      ingestion resulting in more severe symptoms, needs further observation and
      studies that include a larger series.

PMID- 10078165
TI  - Styrene-induced peripheral neuropathy.
AB  - CASE REPORT: Styrene is a colorless, oily liquid most commonly found in paints,
      plastics, and resins. Like many solvents, styrene can cause intoxication and
      central nervous system depression when inhaled in high concentrations for
      extended periods. Rarely, styrene has been implicated as a cause of peripheral
      neuropathy. We describe a case of a previously healthy 57-year-old man who
      developed signs and symptoms consistent with a peripheral neuropathy after
      applying a fiberglass resin to the inside of a septic tank over a 2-day period.
      Nerve conduction tests verified examination findings. Styrene exposure should be
      minimized through the use of respirators and protective clothing to prevent this
      type of toxicity.

PMID- 10078166
TI  - Nonconvulsive status epilepticus in theophylline toxicity.
AB  - CASE REPORT: A 53-year-old cocaine user was on chronic therapy with theophylline,
      albuterol, and ipratropium for asthma and nifedipine for hypertension. Acute
      asthma treatment that increased the serum theophylline to 35 micrograms/mL was
      associated with tonic clonic seizures followed by bizarre, lateralized posturing.
      Electroencephalogram seizure activity lasting 10 days was consistent with
      nonconvulsive status epilepticus, Complex Partial, type II. Theophylline was
      considered the probable instigator of this underdiagnosed neurologic disorder.

PMID- 10078167
TI  - Elemental mercury in the appendix: an unusual complication of a Mexican-American
      folk remedy.
AB  - BACKGROUND: Ingestion of small amounts of elemental mercury is generally thought
      to be harmless. However, in 4 previously reported cases, ingested mercury became
      sequestered in the appendix, causing appendicitis in one. We present a case in
      which elemental mercury was administered as a Mexican-American folk remedy for
      abdominal pain and became sequestered in the appendix. CASE REPORT: A 10-year-old
      Hispanic male presented with 3 days of right-sided abdominal pain, diarrhea,
      fever, and malaise. On admission, his temperature was 41.5 degrees C and he had
      right abdominal tenderness. Urinalysis showed 3 WBCs, 9 RBCs, occasional
      bacteria, and 1+ protein. An abdominal CT scan suggested right focal
      pyelonephritis, but also showed multiple intraabdominal metallic densities. On
      further questioning, the family admitted giving him elemental mercury as a remedy
      for "empacho." He was treated with intravenous ampicillin/sulbactam and
      gentamicin for a focal pyelonephritis. Because of mercury remaining in the
      gastrointestinal tract, activated charcoal and sorbitol were given. By hospital
      day 3, mercury filled the appendix as shown by abdominal radiograph. He was
      placed in the left lateral decubitus position overnight, and by the next morning,
      the mercury partially emptied from the appendix. By hospital day 8, his symptoms
      had resolved and mercury was no longer seen in the appendix. There were only
      minimal increases in urine mercury levels (18 mg/L). At 5-month follow-up, he has
      remained asymptomatic.

PMID- 10078168
TI  - Flour contamination as a source of lead intoxication.
AB  - CASE REPORT: A 43-year-old man was hospitalized because of severe anemia and
      recurrent bouts of abdominal pain over 20 days. There was no known occupational
      exposure to toxins. Concomitantly, the patient's father complained of having the
      same symptoms. Familial lead poisoning was diagnosed when all 6 family members
      tested had high blood leads (31-64 micrograms/dL). RESULTS: Following detailed
      examination of the potential sources common to all members of the household, the
      cause of poisoning was determined to be corn flour containing 38.7 mg/g lead.
      Physicians are reminded to consider lead poisoning in the differential diagnosis
      of individuals with unexplained symptoms, particularly those of abdominal
      discomfort and anemia.

PMID- 10078169
TI  - The electrocardiogram as a diagnostic discriminator for acute tricyclic
      antidepressant poisoning.

PMID- 10078170
TI  - Cottage industry lead poisoning: this time, no paprika.

PMID- 10078171
TI  - Mexican border medications: potential toxicity.

PMID- 10078173
TI  - Reformulated glucagon diluent phenol-free.

PMID- 10078174
TI  - The pneumococcus in the new millennium.

PMID- 10078175
TI  - Hospital in the home: take the evidence and run.

PMID- 10078176
TI  - Disability and work-related injury: time for a change?

PMID- 10078177
TI  - The Lundberg affair.

PMID- 10078178
TI  - Rapidly emerging antimicrobial resistances in Streptococcus pneumoniae in
      Australia. Pneumococcal Study Group.
AB  - OBJECTIVE: To examine the prevalence of resistance in Streptococcus pneumoniae to
      key antimicrobials in Australia during 1997. DESIGN: Prospective, Australia-wide,
      laboratory-based survey. SETTING: 11 microbiology laboratories from seven
      Australian States and Territories (five private laboratories and six public
      hospital laboratories) between March and November 1997. STRAINS: Up to 100
      consecutive, clinically significant strains of S. pneumoniae isolated by each
      laboratory. MAIN OUTCOME MEASURES: Susceptibility to penicillin, amoxycillin
      clavulanate, cefaclor, ceftriaxone, erythromycin, tetracycline, and
      sulfamethoxazole-trimethoprim (cotrimoxazole), measured by a gradient diffusion,
      minimum inhibitory concentration technique. RESULTS: Of 1020 strains, 16.8% had
      intermediate susceptibility to penicillin and 8.6% were resistant. Rates of
      resistance to other drugs were: amoxycillin-clavulanate, 3.1%; cefaclor, 21.4%;
      ceftriaxone, 3.1%; erythromycin, 15.6%; tetracycline, 15.7%; and cotrimoxazole,
      33.4%. Non-invasive isolates harboured more resistances than invasive isolates,
      and resistance was more prevalent in isolates from children under two years.
      Multiple resistance was also common, with 21.2% of strains resistant to two or
      more classes of drug, and 9.3% of non-invasive and 1.7% of invasive isolates
      resistant to four classes. There were no obvious differences in resistance rates
      between private and public hospital laboratories. CONCLUSIONS: Rates of
      antimicrobial resistance are rising rapidly in S. pneumoniae in Australia.
      Recommendations for empiric treatment of invasive and respiratory infection need
      to take account of these changes.

PMID- 10078179
TI  - Hospital in the home: a randomised controlled trial.
AB  - OBJECTIVES: To compare treatment of acute illness at home and in hospital,
      assessing safety, effect on geriatric complications, and patient/carer
      satisfaction. DESIGN: Randomised controlled trial. SETTING: A tertiary referral
      hospital affiliated with the University of New South Wales. PARTICIPANTS: 100
      patients (69% older than 65 years) with a variety of acute conditions, who were
      assessed in the emergency department as requiring admission to hospital.
      INTERVENTIONS: Patients were allocated at random to be treated by a hospital-in
      the-home (HIH) service in their usual residence or to be admitted to hospital.
      MAIN OUTCOME MEASURES: Geriatric complications (confusion, falls, urinary
      incontinence or retention, faecal incontinence or constipation, phlebitis and
      pressure areas), patient/carer satisfaction, adverse events, and death. RESULTS:
      There was a lower incidence of confusion (0 v. 20.4% [95% CI, 9.1%-31.7%]; P =
      0.0005), urinary complications (incontinence or retention) (2.0% [95% CI, -1.8%,
      5.8%] v. 16.3% [95% CI, 6.0%, 26.6%]; P = 0.01), and bowel complications
      (incontinence or constipation) (0 v. 22.5% [95% CI, 10.7%, 34.1%]; P = 0.0003)
      among HIH-treated patients. No significant difference in number of adverse events
      and deaths (to 28 days after discharge) in the two groups was found (although
      numbers were small). Patient and carer satisfaction was significantly higher in
      the HIH group. CONCLUSIONS: Home treatment appears to provide a safe alternative
      to hospitalisation for selected patients, and may be preferable for some older
      patients. We found high levels of both patient and carer satisfaction with home
      treatment.

PMID- 10078180
TI  - Apolipoprotein E polymorphism in indigenous Australians: allelic frequencies and
      relationship with dyslipidaemia.
AB  - OBJECTIVES: To determine the apolipoprotein E (apoE) allelic frequencies and the
      effect of apoE genotype on lipid concentrations in indigenous Australian
      subjects. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: 155 indigenous
      Australians (92 women and 63 men) of mean (+/- standard deviation) age 45 +/- 17
      years (SD +/- 50) were recruited without regard to history of atherosclerotic
      disease, in collaboration with community-based health centres in five indigenous
      communities in south-east Queensland. For comparison, 113 subjects of European
      descent and similar age distribution from the Brisbane and Gold Coast regions
      were also studied. MAIN OUTCOME MEASURES: ApoE allelic frequency; apoE genotype;
      sex; age; diabetes status; body mass index; history of atherosclerotic vascular
      disease; and concentrations of total cholesterol, triglyceride, HDL-cholesterol
      and LDL-cholesterol. RESULTS: The frequency of the apoE4 allele was found to be
      significantly higher in the indigenous subjects than in the subjects of European
      descent (P < 0.001). Among indigenous subjects, those with the apoE4 allele
      tended to have higher triglyceride concentrations and had significantly lower HDL
      cholesterol concentrations than those with the apoE3/3 and 3/2 genotypes.
      CONCLUSIONS: ApoE allelic frequency is likely to be one of the cluster of factors
      contributing to the high cardiovascular mortality of indigenous Australians.

PMID- 10078181
TI  - Characteristics of patients with community-acquired pneumococcal pneumonia.
AB  - OBJECTIVE: To describe the level of activity, independence and demographics of
      elderly people hospitalised with community-acquired pneumococcal pneumonia.
      DESIGN: Prospective descriptive study. SETTING: Seven university-affiliated
      hospitals and three community hospitals. PATIENTS: People aged over 55 years
      admitted to hospital with a clinical history consistent with pneumococcal
      pneumonia, a Streptococcus pneumoniae isolate in blood or sputum, and a chest x
      ray consistent with pneumonia. Significant immunosuppression or certain
      comorbidities (parenchymal lung disease and end-stage renal failure) were
      exclusion criteria. MAIN OUTCOME MEASURE: Level of independence, assessed by
      participation in a range of standardised activities before the patient's illness.
      RESULTS: 82 patients met our case definition. Five refused to participate,
      leaving 77 evaluable patients. The patients had high levels of independence: 64
      (83%; 95% confidence interval [CI], 73%-91%) lived in their own home and 69 (90%;
      95% CI, 81%-95%) participated in regular hobbies. Exercise tolerance was good,
      with 43 (56%; 95% CI, 45%-68%) able to climb a flight of stairs and 59 (76%; 95%
      CI, 65%-85%) able to walk more than 50 m without stopping; 41 (53%; 95% CI, 41%
      64%) could continue further than a kilometre. Mortality was low (9 patients; 12%)
      despite a high rate of bacteraemia (43 patients; 56%). Within the past five
      years, 59 (77%) had been hospitalised and 53 (69%) vaccinated with influenza
      vaccine. Only 7% had ever received pneumococcal vaccination. CONCLUSION:
      Pneumococcal pneumonia is not the "old man's friend". It represents a major cause
      of morbidity and mortality in otherwise well, active and independent older
      Australians. Hospitalisation and attendance for influenza vaccination may
      represent opportunities for pneumococcal vaccination.

PMID- 10078182
TI  - Cat scratch disease diagnosed by polymerase chain reaction in a patient with
      suspected tuberculous lymphadenitis.
AB  - We present a patient diagnosed as having tuberculous lymphadenitis after lymph
      node biopsy and referred for tuberculous therapy. On review, because of recent
      cat exposure, she was tested for cat scratch disease (CSD), but serological tests
      for Bartonella henselae were negative. However, the diagnosis of CSD was
      confirmed, and tuberculosis excluded, by polymerase chain reaction techniques.
      This case serves as a reminder that CSD may mimic tuberculosis histologically and
      that sensitive molecular diagnostic tests are available.

PMID- 10078183
TI  - Primary care psychiatry is not specialist psychiatry in general practice.

PMID- 10078184
TI  - Universal recommendations for sodium intake should be avoided.

PMID- 10078185
TI  - Restriction of salt intake is needed to ameliorate the cardiovascular disease
      epidemic.

PMID- 10078186
TI  - The salt dilemma: some answers, many questions.

PMID- 10078187
TI  - Information technology in medical practice: safety and privacy lessons from the
      United Kingdom.

PMID- 10078188
TI  - Concern over the choice of antivenom for "false king brown snake" bites and a
      plea for a name change.

PMID- 10078189
TI  - Near-patient testing for serum cholesterol: attitudes of general practitioners
      and patients, appropriateness, and costs.

PMID- 10078190
TI  - General practitioners and pathology testing: what else is known of their views?

PMID- 10078191
TI  - Rotavirus infection and rates of hospitalisation for acute gastroenteritis in
      young children in Australia, 1993-1996.

PMID- 10078192
TI  - Detection of chlamydial nucleic acid in follicular trachoma.

PMID- 10078193
TI  - Improving indigenous health: social and environmental factors deserve as much
      attention as health services.

PMID- 10078194
TI  - Not just a renal epidemic among Australian Aboriginals.

PMID- 10078195
TI  - Incidence of mastitis in breastfeeding women during the six months after
      delivery: a prospective cohort study.

PMID- 10078196
TI  - Antigenic variation in malaria: a 3' genomic alteration associated with the
      expression of a P. knowlesi variant antigen.
AB  - Antigenic variation of malaria parasites was discovered in P. knowlesi, using a
      schizont-infected cell agglutination (SICA) assay to detect variant antigens
      expressed at the surface of infected erythrocytes. Later studies utilizing stable
      clones, Pk1(A+) and its direct derivative, Pk1(B+)1+, showed that SICA[+] clones
      express distinct parasite-encoded antigens of approximately 200 kDa. Here we
      identify a P. knowlesi variant antigen gene and cDNA and demonstrate that it
      encodes the 205 kDa variant antigen expressed by B+ parasites. This gene belongs
      to a multigene family, which we term SICAvar. Its ten-exon structure with seven
      cysteine-rich coding modules is unique compared to P. falciparum var genes.
      Further, we highlight a 3' genomic alteration that we predict is related to
      SICAvar gene switching.

PMID- 10078197
TI  - The Drosophila beta FTZ-F1 orphan nuclear receptor provides competence for stage
      specific responses to the steroid hormone ecdysone.
AB  - The acquisition of competence is a key mechanism for refining global signals to
      distinct spatial and temporal responses. The molecular basis of competence,
      however, remains poorly understood. Here, we show that the beta FTZ-F1 orphan
      nuclear receptor functions as a competence factor for stage-specific responses to
      the steroid hormone ecdysone during Drosophila metamorphosis. beta FTZ-F1 mutants
      pupariate normally in response to the late larval pulse of ecdysone but display
      defects in stage-specific responses to the subsequent ecdysone pulse in prepupae.
      The ecdysone-triggered genetic hierarchy that directs these developmental
      responses is severely attenuated in beta FTZ-F1 mutants, although ecdysone
      receptor expression is unaffected. This study define beta FTZ-F1 as an essential
      competence factor for stage-specific responses to a steroid signal and implicates
      interplay among nuclear receptors as a mechanism for achieving hormonal
      competence.

PMID- 10078198
TI  - Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional
      pathway of adipogenesis and insulin sensitivity.
AB  - Mice deficient in C/EBP alpha have defective development of adipose tissue, but
      the precise role of C/EBP alpha has not been defined. Fibroblasts from C/EBP
      alpha(-/-) mice undergo adipose differentiation through expression and activation
      of PPAR gamma, though several clear defects are apparent. C/EBP alpha-deficient
      adipocytes accumulates less lipid, and they do not induce endogenous PPAR gamma,
      indicating that cross-regulation between C/EBP alpha and PPAR gamma is important
      in maintaining the differentiated state. The cells also show a complete absence
      of insulin-stimulated glucose transport, secondary to reduced gene expression and
      tyrosine phosphorylation for the insulin receptor and IRS-1. These results define
      multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation
      between PPAR gamma and C/EBP alpha is a key component of the transcriptional
      control of this cell lineage.

PMID- 10078199
TI  - Bcl-xL prevents cell death following growth factor withdrawal by facilitating
      mitochondrial ATP/ADP exchange.
AB  - Growth factor withdrawal is associated with a metabolic arrest that can result in
      apoptosis. Cell death is preceded by loss of outer mitochondrial membrane
      integrity and cytochrome c release. These mitochondrial events appear to follow a
      relative increase in mitochondrial membrane potential. This change in membrane
      potential results from the failure of the adenine nucleotide translocator
      (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP
      exchange. Bcl-xL expression allows growth factor-deprived cells to maintain
      sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These
      data demonstrate that mitochondrial adenylate transport is under active
      regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression
      permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels
      and allowing mitochondria to adapt to changes in metabolic demand.

PMID- 10078200
TI  - Ras enhances Myc protein stability.
AB  - Various experiments have demonstrated a collaborative action of Myc and Ras, both
      in normal cell growth control as well as during oncogenesis. We now show that Ras
      enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas
      Myc has a very short half-life when produced in the absence of mitogenic signals,
      due to degradation by the 26S proteasome, the half-life of Myc increases markedly
      in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK
      pathway and is not augmented by proteasome inhibition, suggesting that Ras
      inhibits the proteasome-dependent degradation of Myc. We propose that one aspect
      of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of
      transcriptionally active Myc protein.

PMID- 10078201
TI  - RB regulates the stability and the apoptotic function of p53 via MDM2.
AB  - The binding of RB to MDM2 is shown to be essential for RB to overcome both the
      antiapoptotic function of MDM2 and the MDM2-dependent degradation of p53. The RB
      MDM2 interaction does not prevent MDM2 from inhibiting p53-dependent
      transcription, but the RB-MDM2 complex still binds to p53. Since RB specifically
      rescues the apoptotic function but not the transcriptional activity of p53 from
      negative regulation by MDM2, transactivation by wild-type p53 is not required for
      the apoptotic function of p53. However, an RB-MDM2-p53 trimeric complex is active
      in p53-mediated transrepression. These data link directly the function of two
      tumor suppressor proteins and demonstrate a novel role of RB in regulating the
      apoptotic function of p53.

PMID- 10078202
TI  - Mechanism of transcriptional repression of E2F by the retinoblastoma tumor
      suppressor protein.
AB  - The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor,
      critical for normal cell cycle progression. We have undertaken studies using a
      highly purified reconstituted in vitro transcription system to demonstrate how
      pRB can repress transcriptional activation mediated by the E2F transcription
      factor. Remarkably, E2F activation became resistant to pRB-mediated repression
      after the establishment of a partial (TFIIA/TFIID) preinitiation complex (PIC).
      DNase I footprinting studies suggest that E2F recruits TFIID to the promoter in a
      step that also requires TFIIA and confirm that recruitment of the PIC by E2F is
      blocked by pRB. These studies suggest a detailed mechanism by which E2F activates
      and pRB represses transcription without the requirement of histone-modifying
      enzymes.

PMID- 10078203
TI  - Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell
      division.
AB  - We show that several transcriptionally inactive genes localize to centromeric
      heterochromatin in the nucleus of cycling but not quiescent (noncycling) primary
      B lymphocytes. In quiescent cells, centromeric repositioning of inactive loci was
      induced after mitogenic stimulation. A dynamic repositioning of selected genes
      was also observed in developing T cells. Rag and TdT loci were shown to relocate
      to centromeric domains following heritable gene silencing in primary CD4+8+
      thymocytes, but not in a phenotypically similar cell line in which silencing
      occurred but was not heritable. Collectively, these data indicate that the
      spatial organization of genes in cycling and noncycling lymphocytes is different
      and that locus repositioning may be a feature of heritable gene silencing.

PMID- 10078204
TI  - Use of altered specificity mutants to probe a specific protein-protein
      interaction in differentiation: the GATA-1:FOG complex.
AB  - GATA-1 and FOG (Friend of GATA-1) are each essential for erythroid and
      megakaryocyte development. FOG, a zinc finger protein, interacts with the amino
      (N) finger of GATA-1 and cooperates with GATA-1 to promote differentiation. To
      determine whether this interaction is critical for GATA-1 action, we selected
      GATA-1 mutants in yeast that fail to interact with FOG but retain normal DNA
      binding, as well a compensatory FOG mutant that restores interaction. These novel
      GATA-1 mutants do not promote erythroid differentiation of GATA-1- erythroid
      cells. Differentiation is rescued by the second-site FOG mutant. Thus,
      interaction of FOG with GATA-1 is essential for the function of GATA-1 in
      erythroid differentiation. These findings provide a paradigm for dissecting
      protein-protein associations involved in mammalian development.

PMID- 10078205
TI  - Core RNA polymerase from E. coli induces a major change in the domain arrangement
      of the sigma 70 subunit.
AB  - Luminescence resonance energy transfer measurements were used to show that
      binding of E. coli core RNA polymerase induced major changes in interdomain
      distances in the sigma 70 subunit. The simplest model describing core-induced
      changes in sigma 70 involves a movement of the conserved region 1 by
      approximately 20 A and the conserved region 4.2 by approximately 15 A with
      respect to conserved region 2. The core-induced movement of region 1
      (autoinhibition domain) and region 4.2 (DNA-binding domain) provides structural
      rationale for allosteric regulation of sigma 70 DNA binding properties by the
      core and suggests that this regulation may not only involve directly the
      autoinhibition domain of sigma 70 but also could involve a modulation of spacing
      between DNA-binding domains of sigma 70 induced by binding of core RNAP.

PMID- 10078206
TI  - ISWI is an ATP-dependent nucleosome remodeling factor.
AB  - The ATPase ISWI is a subunit of several distinct nucleosome remodeling complexes
      that increase the accessibility of DNA in chromatin. We found that the isolated
      ISWI protein itself was able to carry out nucleosome remodeling, nucleosome
      rearrangement, and chromatin assembly reactions. The ATPase activity of ISWI was
      stimulated by nucleosomes but not by free DNA or free histones, indicating that
      ISWI recognizes a specific structural feature of nucleosomes. Nucleosome
      remodeling, therefore, does not require a functional interaction between ISWI and
      the other subunits of ISWI complexes. The role of proteins associated with ISWI
      may be to regulate the activity of the remodeling engine or to define the
      physiological context within which a nucleosome remodeling reaction occurs.

PMID- 10078207
TI  - Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits.
AB  - Protein complexes of the SWI/SNF family remodel nucleosome structure in an ATP
      dependent manner. Each complex contains between 8 and 15 subunits, several of
      which are highly conserved between yeast, Drosophila, and humans. We have
      reconstituted an ATP-dependent chromatin remodeling complex using a subset of
      conserved subunits. Unexpectedly, both BRG1 and hBRM, the ATPase subunits of
      human SWI/SNF complexes, are capable of remodeling mono-nucleosomes and
      nucleosomal arrays as purified proteins. The addition of INI1, BAF155, and BAF170
      to BRG1 increases remodeling activity to a level comparable to that of the whole
      hSWI/SNF complex. These data define the functional core of the hSWI/SNF complex.

PMID- 10078208
TI  - hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.
AB  - Mismatch recognition by the human MutS homologs hMSH2-hMSH6 is regulated by
      adenosine nucleotide binding, supporting the hypothesis that it functions as a
      molecular switch. Here we show that ATP-induced release of hMSH2-hMSH6 from
      mismatched DNA is prevented if the ends are blocked or if the DNA is circular. We
      demonstrate that mismmatched DNA provokes ADP-->ATP exchange, resulting in a
      discernible conformational transition that converts hMSH2-hMSH6 into a sliding
      clamp capable of hydrolysis-independent diffusion along the DNA backbone. Our
      results support a model for bidirectional mismatch repair in which stochastic
      loading of multiple ATP-bound hMSH2-hMSH6 sliding clamps onto mismatch-containing
      DNA leads to activation of the repair machinery and/or other signaling effectors
      similar to G protein switches.

PMID- 10078209
TI  - Now you sees it; now you don't--the episodic movement disorders.

PMID- 10078210
TI  - Practice nurses in the Waikato, 1991-1992, I: Occupational profile.
AB  - AIMS: To describe the personal characteristics, working conditions, clinical
      activities and professional development of a representative sample of practice
      nurses in the Waikato during the period 1991-1992. METHODS: The data are from a
      survey of practice nurses drawn from a larger study of general practice carried
      out in the Waikato (the WaiMedCa Study). Eighty-nine percent of the 107 practices
      in the region participated in the study. The practice nurse survey was carried
      out on the 189 nurses working in these practices. Of these 149 replied,
      representing a response rate of 79%. RESULTS: On average, there was one nurse for
      each solo practice and two in most other practices. Only two practices--both solo
      -did not employ a nurse. Practice nurses were female and aged between 30 and 50.
      While only one-third had received a postgraduate qualification, two-thirds had
      been to recent professional development courses. The majority had worked as a
      practice nurse for between one and ten years. Nurses averaged just under 15
      telephone contacts a day and 28 face-to-face contacts a week. Nurses' workload
      comprised general measurements and assessments, monitoring and surveillance
      procedures (such as diabetes, asthma and child development), and counselling and
      women's health activities. CONCLUSION: Practice nurses are an accepted and
      essential part of primary health care in New Zealand. However, their potential is
      probably underdeveloped and they could be more fully utilised for a wider range
      of nursing functions.

PMID- 10078211
TI  - Long-term follow-up of the management of benign oesophageal strictures at
      Auckland Hospital 1990-1994.
AB  - AIMS: To audit the success of endoscopic dilatation treatment for oesophageal
      stricture, to determine any predictive factors for multiple dilatations and to
      compare data with a previous series from the same department. METHODS: The
      endoscopy records of 121 consecutive patients with benign oesophageal strictures
      undergoing endoscopic dilatation were reviewed at Auckland Hospital from 1990 to
      1994. RESULTS: Two hundred and thirty-eight procedures were performed with no
      recorded technical failures and minimal morbidity. The follow-up period from
      presentation ranged from 18 to 77 months (median 47 months) and the symptom-free
      period after the last dilatation ranged from 6 to 77 months (median 47 months).
      One hundred and nineteen patients had been followed for 12 months or more since
      their last dilatation. Sixty-three patients (52%) required only one dilatation,
      44 (36%) patients required two to three dilatations and 14 (12%) patients
      required more than three dilatations. There was a trend for patients treated with
      omeprazole to require fewer dilatations than patients treated with H2-receptor
      antagonists (p = 0.07). Patients with tight strictures (< 11 mm) and Barrett's
      oesophagus required more dilatations. CONCLUSIONS: Oesophageal dilatation for
      benign peptic strictures is a safe and effective procedure.

PMID- 10078212
TI  - The 1996 pertussis epidemic in New Zealand: descriptive epidemiology.
AB  - AIM: To describe the 1996 pertussis epidemic. METHODS: Hospitalisation,
      notification and laboratory data were used to describe the 1996 pertussis
      epidemic and compare it with previous epidemics. RESULTS: The 1996 epidemic
      spanned 24 months. The crude hospitalisation rate from 1 June 1995 to 31 May
      1997, was 10.1 per 100,000 person years, being highest for children aged six
      weeks to two months (42 to 90 days old inclusive; 1402 per 100,000). The 1996
      epidemic involved more hospitalisations than the 1991 and 1986 epidemics, and a
      greater proportion for children under the age of one year (77%), compared to
      previous epidemics (60-70%). There were no deaths. Pertussis only became
      notifiable from 1 June 1996. The crude notification rate for the following twelve
      months was 19.8 per 100,000 (equivalent hospitalisation rate 6.7 per 100,000);
      children aged six weeks to two months of age had the highest notification rate
      (531 per 100,000; equivalent hospitalisation rate 1021 per 100,000). In 1996-97,
      children aged under 15 months accounted for 21% of notifications, but 82% of
      hospitalisations. Europeans tended to have higher rates of notifications than non
      Europeans, but lower rates of hospitalisation. CONCLUSIONS: New Zealand continues
      to experience high rates of pertussis as a result of inadequate immunisation
      coverage. The increase in hospitalisations during the 1996 epidemic may reflect a
      real increase in the population-based incidence, or other changes (e.g.
      hospitalisation practice, increase in vulnerable children with poor access to
      primary care). Improved rates, accuracy and completeness of pertussis
      notifications will improve the ability of notification data to accurately
      describe future epidemics and estimate vaccine effectiveness. Further debate is
      required regarding the aims of pertussis immunisation; accelerating the timing of
      the first three doses and adding further doses of pertussis vaccine on the
      national immunisation schedule; and the role of acellular pertussis vaccines. In
      the meantime, the priority must be increasing on-time immunisation coverage.

PMID- 10078213
TI  - Smoking hygiene: a study of attitudes to passive smoking.
AB  - AIM: To study the attitudes and knowledge of adults in the Wellington area about
      the effects of passive smoking and measures to reduce exposure to smoke. METHODS:
      A sample of 200 people, randomly selected in the Wellington area, answered a
      telephone survey on passive smoking. RESULTS: Of the 200 respondents, 160 (80%)
      were males, 40 (20%) were females and approximately one-third (30%) were smokers.
      Most people (85.5%) thought public and private areas should be smoke-free when
      there were children around, but only half (53.5%) thought that smoking should be
      banned in cars when there are passengers. Most people (92.5%) correctly defined
      passive smoking. Half were aware that passive smoking negatively contributed to
      all the following diseases (asthma, cancer, heart disease, respiratory problems)
      and cot death but a higher percentage identified cancer (75.5%) and cot deaths
      (68.5%) specifically. Most smokers reported that they smoke at home or in their
      cars rather than in public places. Half the smokers (50.9%) did not smoke in
      front of children; a further 17.3% reported that they smoked less. CONCLUSIONS:
      In this sample there was a relatively low level of awareness of the effects of
      passive smoking on health and a high prevalence of smoking in the presence of
      children. Smokers and non-smokers were almost equally divided on whether there
      should be a law restricting smoking in private cars, although the majority agreed
      that cars carrying children should be smoke-free. Public health efforts to reduce
      the harm from passive smoking should be focused on discouraging smoking, in
      settings in which children are exposed, including private cars when children are
      passengers.

PMID- 10078214
TI  - Police perceptions of the mental health services and the mentally ill.
AB  - AIM: To explore police officers' perceptions of the mentally ill and of their
      working relationship with mental health services. METHOD: A survey of 200
      randomly selected front-line police officers was carried out over the summer of
      1996/1997. RESULTS: The survey revealed that police identified people in the
      community as mentally ill, dealt with those so identified and related to the
      mental health services in a variety of ways. However, the survey uncovered a
      degree of frustration at the limitations of the Mental Health Act 1992 and the
      limited options available to the police in cases where individuals can not be
      committed. In addition, the survey suggests that many incidents involving the
      police and a person with a mental illness do not involve crime. CONCLUSIONS:
      Although the police are generally happy with the dealings they have with
      providers of mental health services, when police are dealing with those
      identified as mentally ill they are placed in the dilemma of having to liaise
      with other agencies and bodies about something that is not a police problem and
      for which they have little training. It would appear that there is some merit in
      identifying, or lobbying for, agencies who could provide support for those people
      who require help but who do not fulfil committal criteria.

PMID- 10078215
TI  - Problems with meta-analysis.

PMID- 10078216
TI  - Type 2 diabetes, nephropathy and HLA.

PMID- 10078217
TI  - Supine sleeping position and occipital deformities in infants.

PMID- 10078218
TI  - Tribute to Jean Francois Borel: a gentleman and a scholar.

PMID- 10078219
TI  - A few steps along the path to adult transplantation tolerance.

PMID- 10078220
TI  - Cyclosporine: a revolution in transplantation.

PMID- 10078221
TI  - The contribution of cyclosporine A to the understanding and treatment of
      autoimmune diseases.

PMID- 10078222
TI  - Potential of gene transfer for the induction of specific unresponsiveness to
      alloantigens in vivo.

PMID- 10078223
TI  - Future concepts in transplantation.

PMID- 10078224
TI  - On costimulatory signals and T cell tolerance: relevance for transplantation
      immunity.

PMID- 10078225
TI  - Apoptosis of activated peripheral T cells.

PMID- 10078226
TI  - Chronic rejection and its risk factors.

PMID- 10078227
TI  - Islet transplantation.

PMID- 10078228
TI  - Immunosuppression through inhibition of interleukin-2/interleukin-2 receptor
      interaction.

PMID- 10078229
TI  - A tribute to Jean Borel: a transplanter's point of view.

PMID- 10078230
TI  - A tribute to Professor Jean Borel: a patient's point of view.

PMID- 10078231
TI  - The Florence dinner speech, 15th February, 1998.

PMID- 10078232
TI  - All is not well with the artificial heart.

PMID- 10078233
TI  - Electrohydraulic-clamshell heart with energy converter inside the compliance
      reservoir.
AB  - Two new ideas on the electrohydraulic actuation of blood pumps have been
      combined. The first idea was to put the energy converters that propel the
      hydraulic fluid inside the compliance reservoir instead of having them separate.
      Compactness of the device and better cooling of the energy converter by the
      surrounding fluid are two major advantages of this approach. Secondly, we put the
      pumping membrane inside a clamshell that fits over a soft ventricle (1). The
      ventricle can be implanted first, after which the shell is slid over it. These
      two ideas have resulted in devices described in this paper. Preliminary in vitro
      and in vivo data are presented.

PMID- 10078234
TI  - Serum and intracellular detection of cytokines in patients undergoing chronic
      hemodialysis.
AB  - Tumor necrosis factor (TNF) was detected, before and after dialysis, in sera from
      69 patients and, at various times during dialysis, in 28 patients carefully
      selected for the absence of intercurrent illness. Blood samples were also
      sequentially collected for separation of monocytes, and cells were sonicated to
      detect intracellular TNF. Compared with serum levels obtained from 41 healthy
      subjects, basal TNF values of the unselected group of 69 patients were
      significantly higher (p < 0.01), independent of the dialyzer membrane. A
      significant increase in TNF levels by the end of dialysis was found only with
      Cuprophan (p < 0.01). In the selected group of 28 patients, no significant
      changes in TNF values were observed in sequential samples. However, a significant
      increase of intramonocyte TNF levels was found in Cuprophan patients (p < 0.025).
      Soluble interleukin-2 receptor (IL-2R) levels, measured in parallel in sera from
      unselected and selected patients, were found to be very much higher than healthy
      controls without significant changes during the dialysis procedure. While the
      diverse profiles of TNF obtained from differently selected patients suggest that
      mechanisms other than membrane biocompatibility play a role in the appearance of
      these low cytokine levels, the possible nature of uremic toxin for soluble IL-2R
      can be envisaged by detection in dialysis patients.

PMID- 10078235
TI  - Bacteria and endotoxin removal from bicarbonate dialysis fluids for use in
      conventional, high-efficiency, and high-flux hemodialysis.
AB  - The use of bicarbonate-based dialysis fluids in hemodialysis centers in the
      United States has increased with the advent of high-efficiency and high-flux
      hemodialysis. However, bicarbonate dialysis fluids can support rapid bacterial
      growth and high endotoxin concentrations. This study determined the efficacy of
      an ultrafiltration device in reducing the bacterial and endotoxin concentrations
      in bicarbonate dialysis fluids. A polysulfone hollow fiber dialyzer was used to
      ultrafilter bicarbonate concentrate before entering the central proportioner and
      bicarbonate dialysate after exiting the proportioner in single patient dialysis
      machines. Pre- and post-ultrafilter samples were collected for bacterial and
      endotoxin assays over 10 months. Ultrafiltration of bicarbonate concentrate
      reduced bacterial and endotoxin concentrations from 288,330 colony forming units
      (CFU)/ml and 42,804 pg/ml to 0.47 CFU/ml and 109 pg/ml, respectively.
      Ultrafiltration of the dialysate in single patient systems decreased bacterial
      and endotoxin concentrations from 15,889 CFU/ml and 1,746 pg/ml to 0.003 CFU/ml
      and 0.109 pg/ml, respectively. These results demonstrate that ultrafiltration of
      bicarbonate dialysis fluids is effective in reducing bacterial and endotoxin
      contamination inherently associated with the use of bicarbonate-based dialysates.

PMID- 10078236
TI  - Antithrombogenicity of polyacrylonitrile-polyethyleneoxide hollow fiber membrane
      developed for designing an antithrombogenic continuous ultrafiltration system.
AB  - To develop a continuous arteriovenous hemofiltration (CAVH) system, which does
      not need systemic anticoagulation, for patients of acute renal failure having
      bleeding tendencies, a totally antithrombogenic continuous ultrafiltration system
      (ACUS) was designed, which consists of an antithrombogenic polyacrylonitrile
      polyethyleneoxide (PAN-PEO) hollow fiber membrane and ionically heparin-bound
      catheter, tubing, and module header. Antithrombogenicity of PAN-PEO membrane,
      which occupies more than 90% of total inner surface area of ACUS, was considered
      to be due to highly concentrated PEO near the inner surface of the membrane and
      the finely dispersed (less than 500 A) microstructure of the inner surface. ACUS
      was applied to 24 patients without systemic anticoagulation, and one filter
      worked for an average of 32 h without deteriorating their bleeding tendencies.
      Any significant changes in major parameters of biocompatibility during those
      treatments were not observed. More than 200 ml/h of ultrafiltrate was obtained
      even under very low mean blood pressure, less than 70 mm Hg. Based upon these
      results, ACUS was concluded to be suitable for mild and sustained treatment to
      control fluid and electrolyte balance in patients of acute renal failure with
      bleeding complications.

PMID- 10078237
TI  - Artificial connection between glucose sensing and insulin delivery: implications
      of peritoneal administration.
AB  - The replacement of insulinogenic function in insulin-dependent diabetes has to
      restore the feedback between intracorporal glucose and insulin. This has been
      accomplished by the following approaches: (a) the so-called open-loop insulin
      treatment by means of injections or pumps, employing laboratory or other
      extracorporal analytical devices and closing the feedback at large intervals
      only; (b) transplantation of insulin producing tissue and the bioartificial
      pancreas, employing the natural beta-cell both for glucose sensing and insulin
      delivery; (c) implanted artificial drug delivery systems providing chemical
      feedback between intracorporal glucose and insulin release from a nonrefillable
      reservoir of limited capacity; (d) the intracorporal or paracorporal artificial
      beta-cell comprising a glucose sensor (electrochemical or other type) that
      permanently delivers the signal to the computer-controlled insulin pump. This
      artificial device works on the basis of an algorithm of glucose-dependent insulin
      provision, compensating for the lack of other regulators, for the site of insulin
      administration, which is usually posthepatic, and for the kinetic properties of
      sensing system, e.g., a subcutaneous inserted amperometric electrode. Present
      experimental studies show that the pharmacodynamics of peritoneally applied
      insulin may be implemented into a mathematical model of the overall glucose
      insulin system. They include absorption nearly as fast as after intravenous
      application, predominant portal inflow and approximately 30% hepatic removal.
      Feedback-controlled peritoneal insulin administration by means of an artificial
      beta-cell working on peripheral-venous blood glucose monitoring results in normal
      glycemic profiles under basal conditions and during oral glucose loads, if the
      pharmacodynamic properties of the peritoneal route are implemented into the
      insulin dosage algorithm.

PMID- 10078238
TI  - Devices for the treatment of diabetes: today.
AB  - Although single or multiple daily subcutaneous injections of insulin with
      syringes are the mainstay of insulin delivery techniques for the treatment of
      diabetes mellitus, several other methods are now available. The present paper
      will review the main problems occurring with the classical subcutaneous insulin
      therapy and the possible solutions given by the use of new devices, including
      more particularly insulin jet injectors, pens, and portable pumps. This review
      has to be considered as an introduction to the presentations of this symposium
      devoted to implantable pumps, glucose sensors, and artificial pancreas,
      respectively.

PMID- 10078239
TI  - Artificial liver support in acute liver failure: a review of studies at King's.

PMID- 10078240
TI  - Angiographic and pathological studies on regression of coronary atherosclerosis
      of FH patients who received LDL-apheresis treatment.
AB  - We report on the most recent data confirming the angiographic and pathological
      efficacy of LDL-apheresis for coronary atherosclerosis of a familial
      hypercholesterolemia (FH) patient using collected data of a large number of cases
      and especially of one autopsy case. Changes in coronary artery stenosis have been
      assessed angiographically in 37 FH patients in the LDL-Apheresis Regression Study
      (LARS) group of 13 institutions in Japan. Definite regression was observed in 21
      segments by visual and computer analysis. Fourteen of 37 patients (37.8%) who had
      received LDL-apheresis treatment in combination with cholesterol-lowering drugs
      had at least one regressed segment without any progressed segment. We
      pathologically examined at autopsy the coronary arteries in one FH patient who
      had received long-term LDL-apheresis therapy before death. The results revealed
      the process of scarring of atheromatous plaque, suggesting pathological
      regression correlated with the angiographic regression shown in serial angiograms
      taken during LDL-apheresis treatment. It was further suggested that the formation
      of an eccentric thickened wall lesion rich in collagen fiber prevented
      atheromatous plaque from tearing off. Such tearing off might lead to an acute
      coronary event. Aggressive cholesterol-lowering therapy based on LDL-apheresis
      can induce both angiographic and pathological regression in coronary
      atherosclerosis of FH patients.

PMID- 10078241
TI  - Assessment of the biocompatibility and long-term effect of LDL-apheresis by
      dextran sulfate-cellulose column.

PMID- 10078242
TI  - Hematological problems during the use of cardiac assist devices: clinical
      experiences in Japan.
AB  - Hematological changes occurring during use of left ventricular assist devices
      (LVADs) were evaluated in 3 patients suffering from postcardiotomy cardiogenic
      shock. LVAD treatment ranged from 6 to 9 days. During the procedure, no
      anticoagulants were used in the first two cases, while in the third case, a
      protease-inhibiting agent, nafamostat mesilate (FUT-175), was used. In the first
      two cases without any anticoagulants, fibrinopeptide A (FPA) and thrombin
      antithrombin III complex (TAT) increased markedly over the course of LVAD
      treatment, suggesting the excessive activation of the coagulatory system. The
      fibrinolytic system also became activated during LVAD treatment as was indicated
      by a marked increase in FDP-D-dimer and alpha 2 plasmin inhibitor-plasmin complex
      (PIC). Continual decreases observed in Factor XII and prekallikrein indicate that
      the coagulofibrinolytic activation occurring during LVAD treatment is presumably
      the result of contact activation of these factors due to interaction of blood
      with the internal surface of the LVAD. In the third case with FUT-175, both
      coagulation and fibrinolysis were successfully maintained at minimum levels as
      was demonstrated by the extremely low levels of these molecular markers. There
      was also no significant consumption of any contact factors. FUT-175 looks
      promising as an anticoagulant during the use of cardiac assist devices.

PMID- 10078243
TI  - Noninvasive control of cardiac output for alternately ejecting dual-pusherplate
      pumps.
AB  - An artificial heart should be controlled in a noninvasive fashion; the presence
      of the control system should pose no risk to the patient. Ideally, much of the
      control function would be attained passively, by designing the pumps and energy
      converter so that they naturally respond in an appropriate manner to changes in
      the circulation. We present methods of controlling both left-right output balance
      and providing response to changing demands for blood flow for a class of total
      artificial hearts with implanted energy converters. Our balance control actively
      maintains left-right balance, but does so in concert with the natural response of
      the pumps to changes in filling pressures. Cardiac output (CO) can be made to be
      sensitive to right atrial pressure, but peripheral resistance is our usual cue.
      Alternative means of determining the correct cardiac output are discussed.

PMID- 10078244
TI  - Noninvasive monitoring of rotary blood pumps: necessity, possibilities, and
      limitations.
AB  - Although rotary blood pumps do not contain an inherent mechanism for adaptation
      to physiological flow necessities, hitherto only a few efforts have been made to
      obtain robust monitoring and control methods. This paper discusses the necessity
      of noninvasive monitoring of such pumps and the crucial points of sensor
      selection and development. A strategy of monitoring atrial pressure out of the
      data obtained by the collapse of the atrial wall around the inflow cannula and
      initial results on animal tests and computer simulation of this method are
      discussed. This approach might lead to reliable and demand-responsive
      controllers, if some basic criteria are fulfilled.

PMID- 10078245
TI  - Management of intensive-care therapy.

PMID- 10078246
TI  - Efficacy of nafamostat mesilate as a regional anticoagulant in experimental
      direct hemoperfusion and in plasma exchange on humans.
AB  - As an anticoagulant, we compared Nafamostat mesilate (FUT) to heparin in
      experimental direct hemoperfusion (DHP) and studied the efficacy of FUT in
      clinical plasma exchange (PE). In in vitro study, FUT (5 micrograms/ml) inhibited
      the activation of C4 more strongly than heparin (100 U/h), and larger dose of FUT
      (50 micrograms/ml) inhibited the activation of C3. Experimental DHP with FUT on
      jaundiced dogs was safely performed, but not with heparin. Clinical PE with FUT
      was safely performed and the hemostatic condition was not aggravated either
      during or after PE in patients with bleeding.

PMID- 10078247
TI  - Long-term cultures of adult mammalian hepatocytes in hollow fibers as the
      cellular component of extracorporeal (hybrid) liver assist devices.
AB  - A discussion of the treatment of liver insufficiency with extracorporeal (hybrid)
      liver assist devices (LADs) should address a definition of the types of liver
      failure susceptible to being treated by these devices as well as the modalities
      of in vivo and in vitro testing. Relevant to the first subject is the subject of
      pathogenesis of hepatic coma, which should be the target for the design of these
      LADs. Although this modality of therapy is new, it can be predicted that these
      devices will demand minimal safety conditions, i.e., the seeding with cells that
      are not tumorigenic or carrying viral particles. Among other topics to be
      considered in the development of LADs is the proper choice of hollow fiber to be
      used and the testing on proper animal models of hepatic failure. It is our
      philosophy that the long-term culture of adult mammalian hepatocytes in hollow
      fibers is the basis for appropriate designs of this type of temporary liver
      support.

PMID- 10078248
TI  - Pregnancies following implantation of an artificial fallopian tube in rabbits.
AB  - The first cases of pregnancies obtained in vivo in animals after implantation of
      a Teflon artificial fallopian tube model are presented. The Teflon prosthesis was
      implanted into the uterine cornua of rabbits and fixed subcutaneously in the
      abdominal wall. Five to eight blastocysts obtained from donor rabbits were
      transferred through the tubing into each recipient animal's uterus 2 to 14 days
      after placement of the device. On posttransfer day 10, normally developed
      pregnancies were visible and confirmed histologically in 4 of 7 animals.

PMID- 10078249
TI  - New sequential synchronized driving system of intraaortic balloon pumping and
      left ventricular assist device: influence on endocardial viability ratio and
      renal blood flow in their combination.
AB  - Intraaortic balloon pumping (IABP) and left ventricular assist devices (LVAD)
      have shown remarkable progress individually, but how to combine them is still
      unknown. A new sequential synchronized driving system was developed to control
      concomitant use of IABP and LVAD, and then its hemodynamic effectiveness was
      evaluated in swine, especially on endocardial viability ratio (EVR) and renal
      blood flow. This system (pulsatile bypass pump-delay divide system, PBP-DDS) made
      it possible to change the driving phase of IABP and LVAD easily. In 12 swine,
      IABP and LVAD were set up, and these devices were driven in the following 5 modes
      with the PBP-DDS: mode I, IABP alone; mode II, LVAD alone; mode III, IABP + LVAD
      (same timing); mode IV, IABP (early diastole) + LVAD (late diastole); and mode V,
      LVAD (early diastole) + IABP (late diastole). EVR was increased more markedly by
      combined use of both IABP and LVAD (modes III, IV, and V) than by individual
      drive, but there was no significant difference among these modes. On the other
      hand, renal blood flow was decreased so dramatically by the same timing optimal
      counterpulsation method of mode III that it was thought to be harmful for renal
      function. But, the delay divide combination method of modes IV and V resulted in
      no change in the renal circulation. So, it was concluded that this delay divide
      combination mode appeared to be a more promising support to both failed heart and
      renal circulation.

PMID- 10078250
TI  - Techniques for optimization of pulsatile ventricular assist device support.
AB  - For some time now researchers have argued the efficacy of pulsatile versus
      nonpulsatile hemodynamic support. Pulsatile systems, while providing a more
      physiological pumping source, are burdened with a multiparametric output function
      that can greatly affect the utility of such ventricular assist device (VAD)
      support. A simplified approach to the optimization of the pulsatile VADs' output
      function has been developed. This approach yields device outputs of approximately
      5.5 L/min at physiologic pressures while demonstrating clinically acceptable
      blood chemistry. Obtaining this optimal operating point involves the
      determination of the VAD system output function for a range of fill-enhancing
      vacuum settings. A quantitative method for evaluating synchronous versus
      asynchronous pumping modes as related to coronary perfusion is also demonstrated.

PMID- 10078251
TI  - Is a pulsatile cardiac prosthesis a dying dinosaur?

PMID- 10078252
TI  - Artificial liver.
AB  - Without transplantation, approximately 90% of patients with fulminant hepatic
      failure die. If patients receive a liver transplant, there is often a lag between
      the need for and the availability of a donor liver. Therefore, there is a
      definite need for a liver support system to support the patient's own liver
      function in fulminant hepatic failure and while awaiting transplantation. We have
      developed an artificial liver system that not only eliminates lipophilic toxins
      such as phenols, fatty acids, and mercaptans, but also hydrophilic ones such as
      ammonia. This artificial liver system consists of a monitor, an extracorporeal
      blood circuit that uses a hydrophilic polysulfone high-flux dialyzer to remove
      water-soluble metabolites, and a novel hydrophilic liquid membrane filter to
      remove lipophilic toxins. In more than 100 in vitro experiments using porcine (5
      I) blood, the system was evaluated for its ability to remove toxins that are
      normally increased in hepatic failure. We found that phenol, cresol, and short-
      and medium-chain fatty acids can be almost completely eliminated from the blood
      within 5 h. In animal experiments using pigs, we also found no significant
      changes of blood gases, liver parameters, electrolytes, and blood cell counts.

PMID- 10078253
TI  - On-line cell manipulation for cancer treatment.
AB  - We hypothesized that the host immune system is directly stimulated by contact
      between blood and the materials used in blood purification systems. This concept
      has never been applied in therapeutic plasmapheresis. Two new materials have been
      invented since 1983. One of those is lipopolysaccharide (LPS)-immobilized beads,
      which are chemically bonded bacterial LPS (LPS-B). Another is immobilized
      pokeweed mitogen (PWM-B). We studied these two materials for their anti-tumor
      cell activity in vitro and in vivo. Their efficacy on tumor cells was
      demonstrated to be much stronger than that of lymphocyte activated killer (LAK)
      cells. Our new concept was proven to be correct.

PMID- 10078254
TI  - KT/V and protein catabolic rate determination from serial urea measurement in the
      dialysate effluent stream.
AB  - A bloodless technique of evaluating protein catabolic rate (PCR) and KT/V (K,
      clearance; T, dialysis time; V, urea distribution volume) in hemodialysis
      patients is presented based on serial measurement of urea in the dialysate
      effluent stream. PCR follows from equating urea generation and urea removal over
      a 7 day cycle, changes in body stores being comparatively negligible: PCR = 0.026
      [U1 + U2 + U3]/BWdry + 0.17, where U1 is the amount of urea in mmol appearing in
      the dialysate for each session in the 7 day period. KT/V is obtained from the
      slope of the natural logarithm of spent dialysate urea concentration-time plot:
      KT/V = [- slope.T + 3.delta BW/BWdry]/[1 - 0.01786.T(hr], where delta BW = amount
      ultrafiltered in liters. The dialysate-based approach was validated and compared
      with conventional urea kinetic modeling (UKM) for 17 patients studied for three
      consecutive dialyses. The dialysate-based and UKM values of PCR agreed well when
      in vivo clearance values based on total dialysate collection were used for UKM.
      KT/V values agreed poorly on a session-by-session basis but were nearly
      equivalent when averaged for the three dialyses of the week. These findings lay
      the foundation for UKM automation with a urea sensor in the effluent dialysate
      stream.

PMID- 10078255
TI  - The pressure-induced calcium deposition on crosslinked polyurethanes.
AB  - The pressure-induced calcium deposition in crosslinked polyurethane was studied.
      Two polyurethane systems, IPDI-PTMG/PPG-TMP and SMDI-PTMG/PPG-TMP were subjected
      to calcification under induced pressure. Calcium deposition in IPDI polymers was
      linear with the increase of soft segment (PTMG) content whereas in SMDI polymers
      the reverse trend was observed. Decreased phase mixing and hydrophilicity in the
      polymer (SMDI based) having increased soft segment content was attributed to the
      decreased calcification. The enhanced amount of calcium deposition under pressure
      indicates the possible influence of pressure on calcification.

PMID- 10078256
TI  - Evaluation of a polyepoxy compound fixed biological vascular prosthesis and an
      expanded polytetrafluoroethylene vascular graft.
AB  - Antithrombogenicity is one essential requirement for the successful use of small
      caliber vascular prostheses. In this study, a polyepoxy compound fixed,
      heparinized 4 mm diameter Baxter Denaflex vascular graft was evaluated against a
      4 mm diameter Gore-Tex expanded polytetrafluoroethylene (ePTFE) vascular graft in
      the canine model. In addition to the thromboresistant characteristic conferred by
      heparinization, the crosslinking agent allowed the Denaflex graft to retain the
      original color of the native artery. Six centimeter long graft segments were
      implanted into the carotid arteries bilaterally in 5 dogs. The patency rate at 3
      months for the Denaflex graft was 100% (five out of five) whereas in the control
      ePTFE graft, it was 40% (two out of five). The explanted Denaflex grafts
      exhibited softness and flexibility, and their luminal surfaces maintained a white
      color like that before implantation. To the contrary, the patent ePTFE grafts
      felt hard, and red thrombi covered large portions on their inner surfaces. Under
      microscopic observation, neointima formation was limited to regions near the
      anastomotic sites for both types of grafts. This experiment showed that the
      Denaflex vascular graft has an excellent antithrombogenic property and has a
      compliance similar to native arteries.

PMID- 10078257
TI  - Improved postfixation treatment of glutaraldehyde fixed porcine aortic valves by
      monosodium glutamate.
AB  - The use of bioprosthetic valves remains limited due to poor long-term durability
      primarily because of tissue calcification-associated degeneration. Release of
      locally cytotoxic residual aldehyde after glutaraldehyde fixation is one of the
      major causes of this degeneration. In this study, monosodium glutamate was used
      as postfixation treatment to bind residual aldehyde in order to block its toxic
      effects. Thirty-six pieces of fresh porcine aortic valves were fixed by 0.625%
      glutaraldehyde for 14 days, and then 18 of them were treated with 1% monosodium
      glutamate for another 3 days before they were implanted subcutaneously into the
      backs of two groups of rats (n = 9 in each group) for 45 and 90 days,
      respectively. Retrieved specimens were examined grossly, and calcium analysis and
      measurements of tissue collagen and water content were carried out. The results
      showed that, compared with glutaraldehyde fixed specimens, monosodium glutamate
      postfixation treated specimens had less calcification (calcium 104.93 + 50.94
      versus 141.58 +/- 58.10 at 45 days and 103.07 +/- 76.48 versus 199.33 +/- 53.44
      at 90 days, micrograms/mg dry weight, p < 0.01), higher collagen content
      (hydroxyproline 5.50 +/- 1.29 versus 3.58 +/- 1.48 at 45 days and 5.64 +/- 0.87
      versus 4.25 +/- 0.65 at 90 days, micrograms/mg wet weight, p < 0.01), and higher
      water content (68.00 +/- 6.95% versus 61.33 +/- 8.83% at 90 days, p < 0.05) (mean
      +/- SD, paired t test). We conclude that monosodium glutamate couples with
      residual aldehyde, which significantly reduces calcification of glutaraldehyde
      fixed porcine aortic valves while preserving a higher tissue collagen and water
      content after implantation. The preserved tissue collagen and water content of
      the implants is closer to that of unimplanted native valves.

PMID- 10078258
TI  - After a cardiomyoplasty, collaterals from skeletal muscle form to chronic
      ischemic myocardium.
AB  - We measured the collateral formation between skeletal muscle and the heart after
      a latissimus dorsi cardiomyoplasty in an animal model that contained normal,
      chronic ischemic, and infarcted myocardium. The area at risk for ischemia was
      27.0 +/- 3.2% of the left ventricular mass (n = 10, mean +/- SE). In five animals
      the risk area developed predominantly into chronic ischemic myocardium; in five
      others the risk area became an infarct. The collateral blood flow from the
      skeletal muscle to chronic ischemic myocardium (6.05 +/- 1.36 ml/100 g/min, n =
      5) was higher than flow to the infarct (0.46 +/- 0.31 ml/100 g/min, n = 5). The
      collateral blood flow to normal myocardium was minimal (0.04 +/- 0.01 ml/100
      g/min). The collateral blood flow appeared to be concentrated in the outer half
      of the left ventricular wall, with the epicardium having a higher skeletal muscle
      derived collateral blood flow than endocardium (p < 0.05). We conclude that after
      a cardiomyoplasty a collateral blood flow, which approaches clinical
      significance, is preferentially established between skeletal muscle and chronic
      ischemic myocardium. Enhancement of this collateral blood flow might provide a
      means to revascularize patients with presently inoperable coronary disease.

PMID- 10078259
TI  - Critical anatomic dimensions for intrathoracic circulatory assist devices.
AB  - The design of totally implantable circulatory support devices must account for
      the anatomical constraints of the body cavity. To aid development of an
      implantable electrohydraulic ventricular assist device (EVAD), thoracic
      anatomical measurements and fit trials were performed. Various dimensions of the
      thoracic cavity were measured in 19 preserved and fresh cadavers. The mean left
      ventricle apex to chest wall distance was 2.7 +/- 0.2 cm. The mean sagittal
      radius of curvature at the fifth rib was 11.1 +/- 0.4 cm, and the transverse
      radius at the fifth rib was 9.4 +/- 0.3 cm. The mean sternal length was 18.9 +/-
      1.2 cm. Using these measurements a model measuring 17.5 x 10.5 x 3.8 cm was
      designed. This model was placed in the chest of 11 patients undergoing open heart
      surgery. In one patient there was significant lung compression and in another
      hypotension suggesting great vessel compression. Finally, 1 of 11 patients had a
      short sternum and a small thorax, and the device did not fit. In conclusion,
      thoracic measurements may be used in the design of circulatory support devices.
      The model fit adequately in 73% of patient trials.

PMID- 10078260
TI  - Hemodynamic evaluation of a new left ventricular assist device: an integrated
      cardioassist catheter as a pulsatile left ventricle-femoral artery bypass.
AB  - We developed a new left ventricular (LV) assist catheter (transaortic valve from
      LV to femoral artery) that is implemented percutaneously and exerted as a
      synchronous pulsatile partial LV flow support with conventional intraaortic
      balloon pump (IABP) driving system and centrifugal pump system. We investigated
      whether this pulsatile LV-aorta bypass is superior to the IABP from a hemodynamic
      viewpoint. Ten dogs with profound heart failure were placed on this device, and
      hemodynamic measurements were performed under on-off study of this system. The
      results revealed a significant increase of mean aortic pressure, total cardiac
      output, and myocardial blood flow, and a significant reduction of left atrial
      (LA) pressure and LV afterload estimated by diastolic pressure-time index/tension
      time index (DPTI/TTI) measurement compared with baseline values and also with
      IABP exertion alone. These findings suggest that this system is of clinical value
      for supporting an impaired LV that is intractable under IABP counterpulsation.

PMID- 10078261
TI  - C3a and C5a anaphylatoxins bind to heparin-based sorbent in low density
      lipoprotein apheresis: in vitro and in vivo investigations.
AB  - Plasmasorption on a heparin-based sorbent was performed in vitro. It demonstrated
      affinity of the C3a and C5a anaphylatoxins for the sorbent: C3a was removed
      almost completely (97%), and the C5a concentration decreased on average by 55%.
      The plasma level of C3a and C5a complement components was also monitored during
      the procedure of clinical extracorporeal low density lipoprotein (LDL) apheresis
      on the sorbent in patients with familial hypercholesterolemia. A two- to
      threefold increase in C3a (up to 1,500 ng/ml) was observed after plasma
      separation by the IBM 2997 cell sorter. Subsequent processing of the plasma
      through the column led to the low level of C3a detected (less than 50 ng/ml),
      demonstrating significant uptake of C3a by the sorbent column. The removed C3a
      was found in the eluate obtained after regeneration of the sorbent with 2 M NaCl
      solution. No significant increase in C5a was found during the procedure.
      Nevertheless, some C5a was detected in the eluate from the sorbent. The content
      of C3a and C5a in patients blood after the treatment was approximately the same
      as it was initially, 200-500 ng/ml for C3a and less than 10 ng/ml for C5a. The
      removal of C3a and C5a anaphylatoxins by heparin-based sorbent should be regarded
      as an advantage of this type of plasmasorbent.

PMID- 10078262
TI  - Detachable shape-memory sewing ring for heart valves.
AB  - The novel sewing ring concept consists of a detachable ring snap connection
      between valve housing or stent and suture cuff. The suture cuff itself is a
      memory metal ring of nickel-titanium (NiTi) that is embedded within a textile
      fabric torus. After a special training program the ring can assume two geometric
      shapes when alternately cooled and heated. Due to this physical property, the
      sewing ring can be safely fixed within a groove of the housing or stent by
      changing between room and physiological temperature. This allows the surgeon
      first to implant the sewing ring followed by arbitrary positioning and final
      fixation of the valve by the shape-memory effect. Additional advantages are an
      increased stiffening of the valve base for minimizing potential leaflet
      dysfunction, and reduced time and risk of implantation, particularly when a
      reoperation is necessary.

PMID- 10078263
TI  - The valvo-pump, an axial blood pump implanted at the heart valve position:
      concept and initial results.
AB  - The valvo-pump, an axial nonpulsatile blood pump implanted at the heart valve
      position, has been developed. The valvo-pump consists of an impeller and a motor,
      which are encased in a housing. An impeller with 5 vanes (22.0 mm in diameter) is
      used. The impeller is connected to a samarium-cobalt-rare earth magnet direct
      current (DC) brushless motor measuring 21.3 mm in diameter and 18.5 mm in length.
      Sealing is achieved by means of a ferrofluidic seal. A pump flow of 10.5 L/min
      was obtained at a pump differential pressure of 3.3 kPa (25 mm Hg), and a flow of
      4.9 L/min was obtained at 7.0 kPa (53 mm Hg). Sealing was kept perfect against a
      pressure of 29.3 kPa (220 mm Hg) at 9,000 rpm.

PMID- 10078264
TI  - Mechanical circulatory assist by a roller pump system using hydrophilic
      heparinized polymer coated tubing.
AB  - We developed a circulatory assist system driven by a roller pump using
      hydrophilic heparinized polymer coated tubing. This system is easy to handle and
      does not require systemic heparinization. We applied it to 11 patients who failed
      to be weaned from cardiopulmonary bypass after open heart surgery. Left heart
      bypass was employed in 5 patients, right heart bypass in 1, combined left and
      right heart bypass in 2, and venoarterial bypass without oxygenation was done in
      3 patients. The assisting flow rate ranged from 0.8 to 3.2 L/min, and the
      duration of the assist ranged from 5 h to 21 days. Six patients were weaned from
      this support, and 5 were discharged from the hospital. This system is beneficial
      for patients who failed to wean from cardiopulmonary bypass after cardiac surgery
      because of its simplicity and antithrombogenicity.

PMID- 10078265
TI  - Improvement of the hydrodynamic response of a ventricular assist device: a false
      auricle solution.
AB  - We propose a new design of the auricular cannula in ventricular assist devices
      (VADs), consisting of a collapsible large cannula with a capacity approximately
      equal to the ejection volume of the VAD. The device works as a false auricle and
      filters the negative pressure that occurs during diastole. We show that the use
      of this type of cannula improves the hydrodynamic efficiency and the stability of
      the working conditions. Moreover, during chronic implantation in sheep, hemolysis
      stays well below pathological levels. These improvements result in much better
      controllability of the whole VAD.

PMID- 10078266
TI  - Centrifugal blood pump with a magnetically suspended impeller.
AB  - A centrifugal blood pump with a magnetically suspended impeller has been
      developed. It has a single inlet and outlet, and it generates centrifugal forces
      by the rotating impeller. The fluid-dynamical design for inflow and outflow
      through the impeller leads to elimination of the axial force and unbalanced
      radial force acting on the impeller. Consequently, three-component control
      systems, instead of five-component ones, are enough to position the impeller. The
      magnetically suspended impeller rotates by the magnetic coupling with the
      permanent magnets embedded in the outer rotator of the motor. This pump has
      enough performance to function as a blood pump. Further research on the null
      power magnetic suspension and the generation of an efficient rotating magnetic
      field is in progress.

PMID- 10078267
TI  - Development of a flow-transformed pulsatile total artificial heart for total
      implantation.
AB  - To realize a totally implantable total artificial heart (TAH), a new pulsatile
      TAH, the flow-transformed pulsatile TAH (FTPTAH), was developed. The system was
      composed of a single centrifugal pump (CFP) and two three-way valves. One port of
      each three-way valve was connected to the inlet and outlet of a CFP. The other
      two ports of each valve were connected to the right and left atrium, and the
      pulmonary artery and aorta. The CFP can perfuse the pulmonary and systemic
      circulation alternately with pulsatile flow by switching the two three-way
      valves. A prototype and the secondary model in which the solenoid valves and a
      spool valve were included, respectively, were connected to a mock circulatory
      unit with the results that a pulsatile TAH with physiological flow wave form
      could be obtained from a single CFP, about 5 L/min of pulsatile output could be
      obtained alternately on the right and left side by switching the solenoid valves
      or a spool valve, and flow balance between the right and left could be easily
      controlled by the switching duration. The system is feasible for a totally
      implantable TAH because it does not need a compliance chamber and can be
      miniaturized.

PMID- 10078268
TI  - The 1991 Hastings Lecture. The artificial heart: paths, progress and patience.

PMID- 10078269
TI  - Is cardiac function a sufficient criterion to wean a patient from circulatory
      support?

PMID- 10078270
TI  - Oral treatment for jaundice using immobilized bilirubin oxidase.
AB  - Jaundice is characterized by an excessive accumulation of bilirubin in the blood
      and tissues. A novel approach to reduce plasma levels of bilirubin by blocking
      its enterohepatic circulation was investigated. The treatment consisted of oral
      administration of immobilized bilirubin oxidase, which could oxidize bilirubin in
      the intestine to less toxic and more water-soluble products. In vivo
      administration of 0.1 to 2.0 mg/day of immobilized enzyme over a four-day period
      to chronically jaundiced Gunn rats effectively lowered plasma bilirubin levels,
      but only when the molar ratio of total serum bilirubin to rat serum albumin
      (B/RSA) was larger than 0.35. Plasma bilirubin concentration decreased in that
      group from an initial value of 11.3 to 6.3 mg/dl (-40%, n = 5) after eight days.
      This decrease was statistically significant (p < 0.05 by Student's t test).
      However, administration of bilirubin oxidase to rats with a B/RSA ratio less than
      0.35 (n = 10) resulted in no statistically significant change in plasma bilirubin
      concentration.

PMID- 10078271
TI  - Improved function of microencapsulated hepatocytes in a hybrid bioartificial
      liver support system.
AB  - Conventional methods of microencapsulating isolated hepatocytes with Type I
      collagen matrix have provided metabolic liver support in experimental animal
      models of acute liver failure and congenital metabolic liver disease. We compared
      the biological function of transplanted microencapsulated hepatocytes cultured on
      standard Type I collagen (Vitrogen) and a commercially available liver basement
      membrane-like extract from a mouse sarcoma (Matrigel). Isolated hepatocytes were
      microencapsulated with Matrigel and Vitrogen within an alginate-poly-L-lysine
      composite membrane. Isolated encapsulated hepatocytes (IEH) were transplanted
      intraperitoneally into homozygous Gunn rats that exhibit congenital
      hyperbilirubinemia. Control Gunn rats received empty or no microcapsules. Total
      serum bilirubin and conjugated bilirubin in bile were measured at weekly
      intervals for one month. Significant (p < 0.01) decreases in total serum
      bilirubin were observed in all IEH transplanted animals. No such decrease was
      seen in control animals. Gunn rats that received Matrigel had significantly (p <
      0.05) lower serum bilirubin values and significantly (p < 0.05) higher conjugated
      bilirubin in bile than those that received Vitrogen. We conclude that hepatocytes
      microencapsulated with Matrigel functioned better than those with Vitrogen. This
      improved in vivo biological response underscores the importance of using the
      appropriate cell attachment substratum to enhance the function of a hybrid
      bioartificial liver support system based on transplanted hepatocytes.

PMID- 10078272
TI  - Fibronectin binding to gelatin-impregnated Dacron (Gelseal) prostheses.
AB  - Endothelial cell adherence to uncoated gelatin-impregnated Dacron (Gelseal) is
      poor but can be significantly improved by precoating with a suitable basement
      membrane such as fibronectin. To assess the suitability of fibronectin-coated
      Gelseal for endothelial cell seeding, fibronectin binding to Gelseal and its
      dissociation kinetics were investigated. Fibronectin binding was quantified by
      radiolabeling human fibronectin with iodine 125, concentrations of 10, 25, 50,
      150, and 250 micrograms/ml being used to coat Gelseal at 30, 60, and 90 min of
      incubation. The amount of fibronectin bound was directly proportional to the
      concentration used and increased with time of incubation (p < 0.05). However, the
      percentage attachment decreased with increasing concentration (p < 0.001). The
      number of molecules bound per centimeter squared of graft was calculated. In the
      first 30 min, 75% of bound fibronectin was lost after exposure to a flow rate of
      200 ml/min in a pulsatile artificial circulation; thereafter, the fibronectin
      Gelseal bond was stable for up to 2 h.

PMID- 10078273
TI  - In vivo patency of endothelial cell-lined expanded polytetrafluoroethylene
      prostheses in an ovine model.
AB  - The performance of small-diameter vascular prostheses may be improved by
      implantation of grafts lined with endothelial cells. Expanded
      polytetrafluoroethylene (ePTFE) prostheses (4 mm x 40 mm) were coated with
      fibronectin (20 micrograms/ml), seeded with endothelial cells, and cultured for
      48 h to produce a confluent, autologous endothelial cell lining. They were
      implanted as carotid interposition grafts in sheep. Seeded ePTFE grafts were
      compared with nonseeded ePTFE grafts and autologous carotid artery grafts. No
      anticoagulant or antiplatelet therapy was administered, making this a stringent
      test model for the thromboresistance of a small-diameter prosthesis. After 13
      weeks the patencies of seeded, nonseeded, and autologous artery grafts were 16%
      (1/6), 0% (0/6), and 100% (6/6), respectively. The one seeded graft that was
      patent was fully lined with endothelial cells and showed no stenosis. The
      remaining five seeded grafts were occluded by fibrous tissue and displayed
      substantial spindle cell hyperplasia. There was no apparent difference between
      the autologous artery grafts and normal arterial tissue, and the anastomoses
      showed no stenosis. The ovine model provides a conservative test of prosthesis
      survival and may be useful for study of graft failure.

PMID- 10078274
TI  - Effects of a new bone-inducing biomaterial on mesenchymal cells in vitro.
AB  - A purified bone-inducing protein complex (BIC), isolated from bovine bone and
      causing de novo bone formation in vivo, induces defined effects on rat
      mesenchymal cells in vitro. Spindle-like mesenchymal cells growing in monolayers
      change to polygonal cells, forming a multilayered growth pattern. The mesenchymal
      cells acquire alkaline phosphatase activity. Upon culture with BIC, the typical
      collagen Type III deposition of these mesenchymal cells is remarkably reduced
      whereas the collagen Type I expression remains unaffected. All these in vitro
      effects are consistent with the strong bone-forming capacity of BIC in vivo. A
      combination of two cytokines, transforming growth factor beta 1 (TGF beta 1) and
      epidermal growth factor (EGF), shows a similar activity to BIC. Neutralizing anti
      TGF beta antibodies interfere with all in vitro effects of BIC. The
      neutralization of BIC and the inductive capacity of the combination of TGF beta 1
      plus EGF point to the substantial role of TGF beta or TGF beta-like molecules in
      BIC; whether the active polypeptides are identical to TGF beta or somewhat
      structurally homologous to TGF beta remains to be elucidated.

PMID- 10078275
TI  - Bovine pericardium versus porcine aortic valve: comparison of tissue biological
      properties as prosthetic valves.
AB  - The choice of a bioprosthetic valve substitute remains controversial with the
      major concern being primary tissue failure after implantation. We compared
      biological properties of the two most frequently used bioprosthetic valve
      materials, bovine pericardium and porcine aortic valve, before and 90 days after
      subcutaneous implantation in rats. Before implantation, tissue collagen and water
      content were measured in nine pieces of bovine pericardium and porcine valves,
      each fixed in 0.625% glutaraldehyde; calcium, tissue collagen, and water content
      were measured in another nine pieces of the same tissues after 90 days'
      implantation. Bovine pericardium had higher collagen content than that of porcine
      valve (hydroxyproline, 7.98 +/- 0.05* vs. 4.56 +/- 0.02 micrograms/mg, dry
      weight) but lesser water content (72.16 +/- 3.22%* vs. 87.36 +/- 1.62%) before
      implantation (*p < 0.001, mean +/- SD, t test); after implantation, bovine
      pericardium still maintained higher collagen content (hydroxyproline, 4.89 +/-
      0.04* vs. 2.61 +/- 0.06 micrograms/mg, dry weight) but contained the same amount
      of water (60.24 +/- 5.08% vs. 61.43 +/- 9.00%) and calcium (214.43 +/- 34.34 vs.
      199.33 +/- 53.44 micrograms/mg, dry weight) (*p < 0.001, mean +/- SD, t test). We
      conclude that bovine pericardium has superior intrinsic biological properties for
      prosthetic valve manufacture. With proper integration of properties and design it
      will in some applications be superior to the porcine aortic valve.

PMID- 10078276
TI  - A heparin-coated circuit reduces complement activation and the release of
      leukocyte inflammatory mediators during extracorporeal circulation in a rabbit.
AB  - Heparin coating modifies complement activation during extracorporeal circulation
      much more effectively than systemically administered heparin. This rabbit study
      was undertaken to address possible mechanisms responsible for this difference. We
      evaluated the effect of heparin coating on complement activation and subsequently
      the release of leukocyte inflammatory mediators during extracorporeal circulation
      through a simplified circuit. We found in the heparin-coated group a
      significantly reduced complement hemolytic activity (CH50), remaining higher
      leukocyte numbers, significantly decreased release of beta-glucuronidase, and
      most strikingly a complete prevention of tumor necrosis factor (TNF) formation.
      The significantly reduced CH50 activity in the heparin-coated groups indicates
      the reduction of one or more native classical complement products. This could be
      explained by the absorption of complement components by the circuit, which
      results in reduced activity of the complement cascade. We conclude therefore that
      heparin coating reduces complement activation and consequently reduces the
      release of leukocyte inflammatory mediators.

PMID- 10078277
TI  - Thrombus with infection in total artificial heart animals.
AB  - From January 1980 to December 1990, several types of total artificial hearts were
      implanted into 378 animals. In a retrospective study of these animals, 147 (39%)
      were found to have thrombus with infection (T&I). The criteria for diagnosis was
      thrombus formation in the artificial heart and a positive blood culture. The most
      common pathogen isolated from T&I animals was Pseudomonas species. Concurrent
      skin lesions and contamination from the pressure lines may be the primary sources
      of infection, but bacterial translocation from the intestine is another possible
      route. The main pathological findings at necropsies of artificial heart animals
      with T&I were associated with sepsis, congestive heart failure, infected
      thrombus, thromboembolism, and multiple organ infarctions. Most thrombi appeared
      to have originated from valve junctions and connectors. On the basis of these
      observations, a possible mechanism for pathogenesis of T&I has been proposed. The
      results suggest that design improvements and surface modifications to reduce
      thrombosis are important factors that should be carefully considered. Similarly,
      it is important to eliminate the route of entry of pathogenic microorganisms.
      These findings imply that bacterial interaction with thrombus, device related
      bacterial colonization, and host immunomodulation and gut barrier function
      following artificial heart implantation need further investigation.

PMID- 10078278
TI  - Effects of temperature on phagocytosis of human and calf polymorphonuclear
      leukocytes.
AB  - The in vitro effect of temperature on the phagocytic function of human and calf
      polymorphonuclear leukocytes (PMN) was studied. To observe the PMN phagocytic
      function (PPF) at various temperatures, PMN from healthy human and calf donors
      were incubated with serum-opsonized fluorescent latex particles (diameter 1.66
      microns) at 25, 37, 40, 42, 44, or 46 degrees C for 1 h and then observed for
      their phagocytic activity by fluorescent microscopy. At 25, 40, and 42 degrees C,
      human PPF was not significantly different from that at 37 degrees C (87%, 89%,
      and 80% vs. 93%). At 44 degrees C, PPF was noticeably depressed (19%, p < 0.05)
      when compared to that at 37 degrees C. Next, to determine the critical
      temperature and duration of exposure that would irreversibly damage PPF, PMN were
      preincubated at 42, 44, or 46 degrees C for 5-30 min before being subjected to a
      standard phagocytosis assay at 37 degrees C. The human PPF was significantly
      depressed after 30 min at 44 degrees C (33%, p < 0.05) or 10 min at 46 degrees C
      (30%, p < 0.05). In conclusion, neither human nor calf PPF was significantly
      altered at and below 42 degrees C. In contrast, the PPF was irreversibly and time
      dependently damaged when incubated at and above 44 degrees C.

PMID- 10078279
TI  - Small soft left ventricular assist device powered by intraaortic balloon pump
      console for infants: a less expensive option.
AB  - We have developed a pneumatically driven 20 cc soft ventricle for temporary
      right, left, or biventricular assist. The ventricle consists of a vacuum-formed
      soft housing, diaphragm, tricuspid outflow valve, and biflap inflow valve. All
      components including inflow and outflow valves were made with Pellethane. The
      advantages of this blood pump are as follows: it eliminates use of the quick
      connect system and therefore is less thrombogenic; the biflap inflow valve
      provides low inflow resistance; the soft ventricle is easy to implant; the
      polyurethane valves eliminate blood damage and thromboembolism and are low in
      cost compared with mechanical valves; and the vacuum-forming technique is
      reliable, fast, capable of mass production, and therefore inexpensive. We have
      already demonstrated in both in vitro and in vivo experiments that this ventricle
      has excellent hemodynamic performance with less blood damage and thrombogenesis.
      In this study, we evaluated the possible application of a well-defined and widely
      distributed intraaortic balloon pump (IABP) console to the 20 cc left ventricular
      assist device (LVAD) driver. The pump was tested in 6 mongrel dogs (6 to 10 kg)
      using an IABP console. The pump was connected between the left atrium and the
      ascending aorta, placed paracorporeally on the chest wall, and driven at a
      synchronous or fixed rate mode without using vacuum. The 20 cc ventricle could
      maintain the same output as the control output of the natural heart at filling
      pressures of 5 to 10 mm Hg during the entire observation time of 5 h. Thus, this
      20 cc soft ventricle has the potential to be widely used for the treatment of
      severe heart failure in infants because of its excellent hemodynamic performance,
      simplicity, and low cost.

PMID- 10078280
TI  - Percutaneous introduction of left atrial cannula for left heart bypass: utility
      of biplane transesophageal echocardiographic guidance for transseptal puncture.
AB  - For introduction of a left atrial (LA) cannula by the transseptal puncture
      technique, we examined the feasibility of using biplane transesophageal
      echocardiography (B-TEE). A transseptal puncture was performed on 15 patients (3
      male; 12 female; mean age, 48.9 +/- 11.2 years) by B-TEE guide during
      percutaneous transvenous mitral comissurotomy (PTMC). The entire Brocken-brough
      needle and the position of its tip were clearly observed in the right atrium by a
      longitudinal image of B-TEE in all patients (100%), and in 2 (13%) of them also
      by the transverse image of B-TEE. The puncture was about 1 cm caudal from the
      center of the fossa ovalis to avoid any large residual atrial septal defect.
      After transseptal puncture, a Mullin's sheath (7 Fr) and a dilator (14 Fr) were
      inserted into the left atrium in order, and then an Inoue's balloon catheter (12
      Fr) was introduced without difficulty into the left atrium in all patients. With
      contrast injection, the position of the sheaths's tip was clearly confirmed by B
      TEE. Left heart bypass support (left atrial-femoral artery bypass or AAB) was
      performed on 2 patients after percutaneous introduction of the LA cannula using
      this technique, and both were successfully supported and survived. With B-TEE
      guidance, the Brockenbrough atrial septal puncture and introduction of the LA
      cannula into left atrium can be performed easily. Thus, percutaneous left heart
      bypass can be set up quickly and safely even in an intensive care unit or
      outpatient emergency room without radiographic guidance.

PMID- 10078281
TI  - Diminished release of atrial natriuretic factor in calves with a total artificial
      heart.
AB  - Venous hypertension after total artificial heart (TAH) replacement, a common
      problem in humans as well as experimental animals, is thought to be related to
      reduced release of atrial natriuretic factor (ANF) due to atrial damage. To
      verify this hypothesis, we stimulated the release of ANF in 6 calves before (-7
      days) and after TAH replacement (+25, +50, +80, and +100 days) by the rapid (+ =
      10 min) infusion of 2 L of Ringer's solution. In normal calves (-7 days) this
      procedure induced a rise in plasma concentration of ANF from 18.5 +/- 12 to 31.6
      +/- 12 pmol/L (p < 0.05). After TAH the ANF release continuously decreased
      (analysis of variance, p < 0.02). Thus, ANF increased by 9.8 +/- 9.3, 6.8 +/-
      17.5, 0.4 +/- 5.2, and 0.5 +/- 3.2 pmol/L at days 25, 50, 80, and 100,
      respectively. The central venous pressure increased by 3.4 +/- 1.5 mm Hg (before
      TAH) and by 6 +/- 2.9 mm Hg (after TAH) during this procedure. A decrease in
      plasma concentrations of aldosterone, most likely due to extracellular volume
      expansion and a decrease in total protein plasma concentrations and in hematocrit
      due to the dilution of blood, was seen in each experiment. Necropsy demonstrated
      massive atrial dilatation and myocardial dystrophy with atrial fibrosis. ANF
      granules were present to a small extent in every calf. We conclude that rapid
      intravenous infusion is an adequate stimulus to release ANF in normal calves.
      After TAH implantation the release of ANF by high venous pressure declines
      although ANF granules are still present in the damaged atrial stumps. Therefore,
      the loss of stimulated ANF could contribute to the observed increase in venous
      pressure in TAH calves although other pathophysiologic mechanisms cannot be
      excluded.

PMID- 10078282
TI  - Development of a totally implantable electromechanical total artificial heart:
      Baylor TAH.
AB  - A totally implantable, one-piece, electrome-chanical total artificial heart (TAH)
      intended for permanent human use has been developed. It consists of left and
      right pusher-plate pumps (63 cc design stroke volume) sandwiching a thin center
      piece with a compact electromechanical actuator. The pusher-plates are shaped
      conically to accommodate an actuator in the space between them. The actuator
      consists of an efficient and durable planetary roller screw and direct current
      brushless motor. The left master alternate pumping mode was implemented utilizing
      the left pump pusher-plate position signal. The blood-contacting surface was
      coated with a dry gelatin to yield long-term clot-free performance. Trileaflet
      tissue valves of 27 and 23 mm are used in the inflow and outflow ports. The
      diameter and thickness of the TAH are 97 and 82 mm. the overall volume is 510 cc,
      and the weight is 620 g. Anatomic fit was confirmed in 26 heart transplant
      recipients (body weight 78 kg and surface area 2 m2) without compressing adjacent
      organs. The pump performance study revealed that the TAH can yield outputs of 3-8
      L/min against the 100 mm Hg afterload with 1-10 mm Hg filling pressure. The input
      power to the motor ranged from 7 to 12 W, with an efficiency of 18% to 14%. A one
      week in vivo calf study demonstrated adequate performance of the TAH,
      particularly the regulation of atrial pressures. Good anatomic fit and good
      biocompatibility were also demonstrated.

PMID- 10078283
TI  - Development of totally implantable electromechanical artificial heart systems:
      Baylor ventricular assist system.
AB  - An implantable electromechanical ventricular assist system (VAS) intended for
      permanent use has been developed. It consists of a conically shaped pumping
      chamber, a polyolefin (Hexsyn) rubber diaphragm attached to a conically shaped
      pusher-plate, and a compact roller-screw actuator. Design stroke volume is 63 ml.
      The device weighs 620 g, and has a total volume of 348 ml. The pump can provide 8
      L/min flow against 120 mm Hg afterload with a preload of 10 mm Hg. The inner
      surfaces are biolized by dry gelatin coating, with inflow and outflow ports
      accommodating tissue valves. Three subacute in vivo validation studies have been
      conducted in calves up to two weeks. The entire system functioned satisfactorily
      in both the fill/empty and the fixed-rate modes. There was no thromboembolic
      complication without anticoagulation. The pump showed reasonable anatomical fit
      inside the left thorax. This VAS is compact, efficient, quiet, and easy to
      control.

PMID- 10078284
TI  - Raising plasma phosphorus levels by phosphorus-enriched, bicarbonate-containing
      dialysate in hemodialysis patients.
AB  - In 6 hemodialysis patients, enriching the "base concentrate" of a bicarbonate
      containing dialysate-generating system with phosphorus succeeded in raising
      plasma phosphorus levels.

PMID- 10078285
TI  - In vitro buffering capacity of residual peritoneal dialysate fluid: implications
      for peritoneal dialysis therapy.
AB  - The buffering capacity of the residual peritoneal dialysate fluid from each of 5
      patients undergoing continuous ambulatory peritoneal dialysis was assessed by
      titrating with fresh, conventional, acidic, and lactate-containing peritoneal
      dialysis solutions. It was found that residual fluids had considerable buffering
      capacity.

PMID- 10078286
TI  - Assessment of an extracorporeal liver assist device in anhepatic dogs.
AB  - We have used an anhepatic dog model to demonstrate the efficacy of a
      bioartificial liver assist device. Six dogs underwent total hepatectomy. Three
      received only medical care (controls) while the remainder were connected to an
      extracorporeal liver assist device (ELAD). The control dogs failed to regain
      consciousness after anesthesia although all lived 4-5 h postoperatively. Plasma
      ammonia concentration increased by an average of 250 mumol/L between the end of
      surgery and the demise of the animals. The treated dogs lived 3-12.5 h, and 2 of
      them required repeated doses of thiamylal sodium to maintain sedation. Plasma
      ammonia concentration was unchanged after connection to the ELAD except in the
      longest survivor, whose ammonia began to rise after 8 h on the ELAD. The short
      survival in the other 2 treated dogs was the result of uncontrolled
      intraabdominal bleeding. This device is capable of replacing the metabolic
      function of the liver, and might provide hepatic support in patients awaiting
      transplantation or in fulminant hepatic failure.

PMID- 10078287
TI  - In vitro study of multicellular hepatocyte spheroids formed in microcapsules.
AB  - To make highly differentiated encapsulated hepatocytes, we formed hepatocyte
      spheroids in microcapsules in cultures. Hepatocytes isolated from rats were
      encapsulated in alginate-poly-L-lysine artificial cells and cultured under
      different medium conditions. When high molecular weight poly-L-lysine was used to
      make the capsule membrane, the hepatocytes aggregated and formed spheroids inside
      microcapsules within 48 hs. We studied the viability and function of encapsulated
      hepatocyte spheroids; free hepatocyte spheroids; nonaggregated encapsulated
      hepatocytes; and free hepatocyte monolayers. Cell viability and protein-producing
      ability were monitored for up to 30 days. Hepatocyte spheroids in the
      encapsulated or free form remained viable and continued to secrete proteins
      throughout the 30 days of observation. The viability and function of
      nonaggregated hepatocytes in the encapsulated or free form declined rapidly.
      These results suggest that the tridimensional structure of the spheroids may be
      important in maintaining the viability and function of encapsulated hepatocytes.

PMID- 10078288
TI  - Properties of hemoglobin and dextran-hemoglobin rightshifted by oxidized inositol
      tetrakisphosphate.
AB  - Phytate was digested by wheat bran phytase to yield inositol tetrakisphosphate.
      Periodate-oxidized inositol tetrakisphosphate (oxyIP4) was coupled by means of
      reductive alkylation to hemoglobin and the covalent dextran-hemoglobin conjugate
      to yield the rightshifted (rs) compounds rsHb and rsDxHb, respectively. The
      variations of the oxygen dissociation curves of these molecules with pH and
      temperature were compared to those of hemoglobin. The variations with pH were
      found to be less pronounced for these rightshifted forms. An extensive decrease
      in the half-saturation oxygen tension was observed, however, with both rsHb and
      rsDxHb, as in the case of unmodified Hb. Modification of hemoglobin by oxyIP4 at
      the polyphosphate site was suggested by the lack of a further rightshifting
      effect of phytate on rsHb, and by the similarity between the difference spectrum
      of rs-methemoglobin and the difference spectrum induced by the addition of
      phytate.

PMID- 10078289
TI  - Wearable air supply for pneumatic artificial hearts and ventricular assist
      devices.
AB  - An experimental wearable air supply for pneumatic artificial hearts and
      ventricular assist devices has been built and tested. The unit eliminates the
      need for tethering to a large, stationery driver. The miniaturized air supply is
      designed for ambulatory patients with implanted pulsatile pneumatic total
      artificial hearts (TAH) or pneumatic left-ventricular assist devices (LVAD), to
      permit mobility in clinical and home settings. The device has major short-term
      utility as a supply for pneumatic TAH or VAD bridges in patients awaiting heart
      transplants. The system design for the wearable driver includes a novel, fast
      rotary compressor, driven by a brushless direct current (DC) motor to supply air
      to the ventricle through an electromagnetically actuated directional valve, all
      controlled by a microcomputer. Stroke volume from 0 to 200 cc; pulse rate from 60
      to 160 bpm, and duty cycle from 33% to 50% are selected on a keyboard, and the
      selected or measured parameters can be shown on a liquid crystal display. For
      control of delivery from a single ventricular assist device, stroke volume is
      controlled by variation of compressor speed. In the wearable air supply for a
      TAH, a single compressor drives both ventricles alternately through a double
      acting directional valve. Air volume delivered to the left ventricle is adjusted
      by variation of compressor speed, and air volume to the right ventricle by
      variation of ejection time. The effect on blood flow rate of the lower impedance
      to the right ventricle is compensated by provision of a two-stage compressor, in
      which a single stage drives the right ventricle, and both stages connected in
      parallel drive the left ventricle. The overall dimensions of the prototype air
      supply for driving either a TAH or LVAD are 4.5 by 7.8 by 4.5 inches, including
      an emergency battery with a duration of 15 to 30 min depending on load. The
      weight is presently 5.5 lb, but this will be reduced in a production design and
      for a dedicated LVAD air supply. The size and weight of a separately worn,
      rechargeable battery pack depend on the load and desired duration of operation.

PMID- 10078290
TI  - Is it artificial blood? No, it should be oxygen-carrying macromolecules.

PMID- 10078291
TI  - Bacteriology of hemodialysis fluids: are current methodologies meaningful?
AB  - Reports of increasing endotoxic reactions in dialysis centers using high-flux
      dialyzers and high contamination in liquid bicarbonate concentrates have resulted
      in concern for the microbial contamination of dialysate. The influence of salt
      supplemented media on the recovery of bacterial contaminants from the fluids used
      in hemodialysis has been examined. This study found a negative influence of a 2%
      NaCl supplementation of growth media for both purified water and dialysate. Salt
      supplemented pour plate cultures of bicarbonate concentrate samples were not
      statistically different from nonsupplemented cultures (p = 0.2). The influence of
      the bicarbonate salt on recovery in the pour plates was not addressed. The
      different media recommended for monitoring microbial contamination of dialysis
      fluids were compared. As previously reported, both water and dialysate collected
      from a relatively large geographic area showed higher recoveries on Reasoner's
      R2A agar than on media recommended by the Association for Advancement of Medical
      Instrumentation (AAMI) standards (p < 0.0001). Standard methods agar (SMA) and
      trypticase soy agar (TSA) produced the next highest recovery for water and
      dialysate, respectively. The higher recoveries generally observed on R2A or SMA
      suggest that to provide better patient safety these media should be selected for
      monitoring bacterial contamination of water, and R2A, SMA, or TSA for dialysate.
      The variability in the species identified across the three fluids and variability
      in counts observed in the different fluids suggest that significant dialysate
      contamination may occur from sources other than the water and bicarbonate
      concentrates.

PMID- 10078292
TI  - Pharmacokinetics and dosage adjustment of antibiotics during continuous
      extracorporeal lung assistance and hemofiltration.
AB  - Fifty-eight patients undergoing continuous volume-controlled hemofiltration
      (CVHF) and extracorporeal lung assistance (ECLA) received drug therapy determined
      by use of a new predictive algorithm in a validation study. Amikacin, netilmicin,
      tobramycin, ceftriaxone, vancomycin, and teicoplanin doses were given as
      predicted from clinical parameters. Corrections were necessary in 15 cases (e.g.,
      CVHF 68% and ECLA 82% precision). There were no statistical differences between
      predicted and monitored drug doses. The correlation coefficient gave r2 = 0.921.
      Preliminary results from not yet analyzed drugs (ceftriaxone, teicoplanin) fit
      well into the curve. Because of rapid intraindividual changes, toxic drugs should
      continue to be monitored.

PMID- 10078293
TI  - Effects of pyridoxalated hemoglobin polyoxyethylene conjugate on diameter of rat
      mesenteric arterioles in situ.
AB  - The effects of exchange transfusion (ET) with a modified hemoglobin
      (pyridoxalated hemoglobin polyoxyethylene conjugate, or PHP) on endothelium
      dependent relaxation of microvasculature were examined in rat mesenteric
      arterioles using image-splitter television microscopy. To examine the endothelium
      dependent relaxation, we applied acetylcholine (ACh) to arterioles preconstricted
      with norepinephrine (NE) and measured changes in arteriolar diameter. Topical
      application of NE (6 x 10(-8) to 6 x 10(-6)M) decreased the diameter of the
      arterioles dose-dependently to a mean of 45% (SE +/- 4%, n = 6) of the control.
      Topical application of ACh (7 x 10(-8) to 7 x 10(-6)M) increased the diameter of
      the arterioles preconstricted with NE in a dose-dependent manner and almost fully
      reversed the NE-induced decrease in diameter. ET with 6% PHP solution (30 ml/kg)
      induced an increase in the mean arterial blood pressure (MABP) from 117 +/- 5 to
      132 +/- 4 mm Hg (n = 6, p < 0.05), with a concomitant decrease in diameter of
      arterioles, from 22.6 +/- 2.5 to 19.8 +/- 2.7 microns (p < 0.05). The MABP and
      arteriolar diameter gradually returned to the control level within 30 min after
      ET. Arteriolar changes in diameter in response to NE and ACh examined 30 min
      after ET were similar to those of the control. ET with 6% stroma-free hemoglobin
      (SFH; 30 ml/kg) did not alter arteriolar changes in diameter in response to NE
      and ACh. Results suggest that circulating PHP and SFH moieties do not interfere
      with endothelium-derived relaxing factor(s) induced by ACh in rat mesenteric
      microvasculatures in situ.

PMID- 10078294
TI  - Elimination of an artificial immune complex by plasmapheresis in rabbits.
AB  - The behavior of an artificial immune complex was investigated in 15 rabbits. The
      immune complex was labeled with iodine-125 (125I). The advantage was that the
      immune complex could not be metabolized without being eliminated by the kidney.
      This artificial immune complex was injected in a dosage of 0.8 microgram, in 2
      rabbits, 5.0 micrograms in 4 rabbits, 10 micrograms in 3 rabbits, 20 micrograms
      in 2 rabbits, and 40 micrograms in 4 rabbits on two consecutive days. One group
      (n = 9) was treated with plasmapheresis: the other (n = 6) was a control group
      that did not undergo plasmapheresis. A miniaturized plasmapheresis system
      eliminated the immune complex very effectively with an average exchange volume of
      95.7 ml per treatment. The increasing concentration of the immune complex in the
      blood before the next plasmapheresis treatment was probably an expression of
      mobilization of the immune complex from different organs. The animals of the
      plasmapheresis group were in better condition than the control group.

PMID- 10078295
TI  - Plasmapheresis in newborns with hyperbilirubinemia.
AB  - With a miniaturized plasmapheresis system consisting of a double head pump and
      balancing pump, extracorporeal detoxification treatments such as plasmapheresis,
      hemofiltration, and hemodialysis were carried out. In total 15 premature infants
      and newborns with Rherythroblastosis and hyperbilirubinemia were treated using
      this miniaturized system. The average birth weight of the 15 patients was 2,386
      g. With a main blood flow of 5.3 ml/min and a filtrate flow of 1.3 ml/min, an
      average of 192.4 ml of plasma per treatment was exchanged. In all patients 1 to
      10 plasmapheresis treatments were necessary to reduce the mean serum bilirubin
      from 15.6 +/- 4.8 to 7.3 +/- 3.2 mg/dl, and after several days the serum
      bilirubin subsequently normalized in 12 patients, who improved. Three patients
      died 5 to 18 days after birth as a result of their primary disease and
      immaturity. For vascular access small catheters were inserted in the umbilical or
      the femoral vein. All treatments were well tolerated by the patients.

PMID- 10078296
TI  - Effects of synchronous pulsatile extracorporeal membrane oxygenation in an
      endotoxin-induced shock model: an experimental study.
AB  - A synchronous pulsatile venoarterial device for extracorporeal membrane
      oxygenation (ECMO) was designed to accomplish more effective circulatory support
      for neonates. The effect of this device was studied using an endotoxin-induced
      shock model, compared with conventional nonpulsatile ECMO. Twenty puppies
      weighing 1.6 to 4.0 kg were given endotoxin (5 mg/kg) intravenously. Thirty
      minutes after the administration of endotoxin, 10 were placed on pulsatile ECMO,
      and the others were placed on nonpulsatile ECMO, and they were studied for an
      additional 180 min. Peak blood pressure, arterial pH, base excess, and renal
      blood flow were significantly higher in the pulsatile group than in the
      nonpulsatile group. Serum lactate and serum noradrenaline were significantly
      lower in the pulsatile group than in the nonpulsatile group. These results
      indicate that pulsatile ECMO may provide more effective cardiopulmonary support
      in the treatment of neonates with serious circulatory failure that has failed to
      be supported by nonpulsatile ECMO.

PMID- 10078297
TI  - Noninvasive color Doppler inspection of small-diameter vascular grafts implanted
      in canine carotid and femoral arteries.
AB  - To noninvasively evaluate a small-diameter vascular graft (approx. 4 mm in
      diameter) developed for coronary artery bypass application, a state-of-the-art
      color Doppler flow mapping system was applied to inspect various grafts implanted
      in 5 canines. The grafts, including Denaflex, Gore-Tex ePTFE, and Bioflow, were
      implanted interpositionally in the carotid and femoral arteries. Inspections were
      conducted with a 5 MHz linear vascular transducer at 6 weeks postimplantation and
      12 weeks postimplantation, immediately prior to retrieval. In the carotid artery
      position, all 5 Denaflex grafts were patent throughout the implantation period
      while 2 of the 5 Gore-Tex grafts were occluded at 6 weeks, and 1 more was
      occluded at 12 weeks. In the femoral artery position, all 5 Denaflex grafts were
      patent at 6 weeks; however 2 were occluded at 12 weeks. For the Bioflow grafts at
      6 weeks, 3 were patent, and 2 were occluded. The same results were observed at 12
      weeks. The color Doppler inspection results indicated a higher patency rate in
      the carotid artery position than in the femoral artery position. Furthermore, the
      volumetric flow rate and the wall shear stress measured with the pulsed Doppler
      in the carotid artery were greater than in the femoral artery. These findings
      suggest that the hemodynamic "environment" in which the graft was implanted may
      affect the graft patency rate. The Doppler inspection results obtained at 12
      weeks, identical with those observed after retrieval, demonstrated that color
      Doppler flow mapping is a reliable method to noninvasively inspect blood flow
      through small-diameter vascular grafts.

PMID- 10078298
TI  - A ferrofluidic actuator for an implantable artificial heart.
AB  - The feasibility of using a ferrofluidic actuator for an artificial heart was
      studied. A ferrofluidic actuator directly drives magnetic fluids simply by
      applying a magnetic field to the ferrofluids and does not require a bearing.
      Magnetic fluid in a U-shaped glass cylinder was placed in an air gap of a
      solenoid. When a magnetic flux of 0.32 T was applied to the interface of the
      ferrofluid and air, the ferrofluid was displaced and a pressure of 7.58 kPa (57
      mm Hg) was obtained. An array of three poles of solenoids was mounted near the U
      shaped glass cylinder. The solenoids were sequentially activated and deactivated.
      A pressure of 9.98 kPa (75 mm Hg)/-1.33 kPa (-10 mm Hg) was obtained.
      Calculations indicate that a magnetic flux of 0.49 T is enough to obtain a
      pressure of 13.3 kPa (100 mm Hg). A ferrofluidic actuator is promising for use
      with an implantable artificial heart.

PMID- 10078299
TI  - Three-dimensional imaging of mitral and tricuspid annuli for total artificial
      heart implantation.
AB  - The establishment of a method to clarify the three-dimensional interrelations
      among the mitral annulus, tricuspid annulus, ascending aorta, and main pulmonary
      artery, which constitute the interface between the human and total artificial
      heart (TAH), is essential to the design of the TAH. In a previous study based on
      transverse magnetic resonance (MR) images of a live human heart, reconstructed
      images of mitral and tricuspid annuli were found to be deformed. The present
      study of cadaver and beating hearts revealed that the optimal conditions for
      atrioventricular annular reconstruction of a beating heart with electrocardiogram
      gated MR imaging include use of four-chamber imaging, 5 mm slice thickness, and a
      slice interval ranging from 5 to 7 mm. Under these conditions, the mitral and
      tricuspid annuli of 3 beating hearts were reconstructed successfully. It was
      recognized that during the systolic phase the mitral and tricuspid annuli move
      anteriorly, leftward and downward, and that in late systole the right lateral
      margin of the tricuspid annulus is close to the sternum.

PMID- 10078300
TI  - Gas-exchange function of a preprimed pediatric oxygenator stored for one year for
      emergency cardiopulmonary bypass.
AB  - To save priming time and perform more rapid initiation of emergency
      cardiopulmonary bypass for acute cardiopulmonary failure, an extracorporeal
      circuit with a hollow-fiber oxygenator (EL-2000 for pediatric use; Kurary Co.
      Ltd., Osaka, Japan) was preprimed, and the gas-exchange function was evaluated
      after 1 year of storage. EL-2000 has a dense polyolefin membrane with a surface
      area of 0.3 m2. When the bypass flow rates were 250, 500, 1,000, and 1,500 ml/min
      with 100% oxygen at the same flow rate as the bypass blood flow (namely, V/Q = 1)
      to the oxygenator, oxygen transport rates of the stored oxygenator were 19.6 +/-
      0.3, 38.3 +/- 0.41, 64.4 +/- 0.9, and 76.4 +/- 2.7 ml/min (n = 5, mean +/- SD),
      respectively. PCO2 differences between pre- and postoxygenator blood (delta PCO2)
      were 18.6 +/- 1.4, 12.0 +/- 1.6, and 4.4 +/- 1.2 mm Hg at V/Q = 1 and the same
      bypass blood flow rates, respectively, excluding 1,500 ml/min, the data for which
      were excluded because of preparatory failure. PCO2 removal indices (defined as
      the ratio of delta PCO2 to PCO2 in preoxygenator blood) were 0.45 +/- 0.03, 0.29
      +/- 0.12, and 0.10 +/- 0.03, respectively. Though the evaluation was done using
      only a single oxygenator, we feel strongly that the gas-exchange function of the
      preprimed dense-membrane hollow fiber oxygenator will be preserved even after 1
      year of storage.

PMID- 10078301
TI  - Evaluation of high-frequency jet ventilation in oxygenation through an artificial
      membrane lung.
AB  - The membrane oxygenator often develops impaired gas exchange after prolonged use
      because plasma proteins adhere to the membrane's surface and leak through its
      micropores. This study was performed to examine the efficacy of high-frequency
      jet ventilation (HFJV) in minimizing these problems in a "flat plate" type of
      membrane oxygenator. We first vibrated the membrane of the oxygenator by HFJV
      from 1 to 10 Hz to find the frequency most effective for optimal gas exchange in
      animals with partial extracorporeal circulation. These studies suggested that 6
      Hz HFJV was preferable in our model. We subsequently performed in vivo
      extracorporeal oxygenation in dogs for 8 h using the membrane oxygenator with or
      without 6 Hz HFJV. Although the gas exchange capacity within the first 8 h was
      similar in the two groups, after 6 h a significant decrease in the red blood cell
      count and in the hematocrit was found in the group not receiving HFJV. Scanning
      electron microscopic examination of the membranes after 8 h of use disclosed that
      the membrane from the group receiving HFJV had less plasma protein and fibrin
      adhesion than that from the group not receiving HFJV. Moreover, it appears that
      with prolonged extracorporeal oxygenation, 6 Hz HFJV also protects against a
      decrease in the hematocrit of the passed blood and might lead to enhanced gas
      exchange. Our data suggest that good gas exchange can be maintained for periods
      even longer than 8 h if HFJV is used in conjunction with the membrane oxygenator.

PMID- 10078302
TI  - Optimum albumin concentration of supplementation fluid for double filtration
      plasmapheresis.
AB  - Until recently, the albumin concentration of supplementation fluid for double
      filtration plasmapheresis (DFPP) has been empirically determined. Inadequate
      albumin infusion often leads to hypoproteinemic symptoms such as edema. In the
      current study, an aimed condensation coefficient (CCaimed) was introduced in an
      attempt to estimate the appropriate plasma albumin level for each patient. This
      coefficient is theoretically derived from a one-compartment model for the
      patient's plasma albumin: CCaimed = CS/CD = 1 - (1 - CR)/[1 - exp(- CC.VR)] where
      CD and CS are albumin concentrations in discarded plasma and supplementation
      fluid. CR is the change ratio of albumin concentration in the patient's plasma
      during a DFPP treatment, and VR(= VS/VP) is the ratio of supplementation fluid
      volume (VS) to the patient's total plasma volume (VP). And CC denotes the albumin
      condensation coefficient in a DFPP line, which depends on the filtration fraction
      of the plasma fractionator (FFPF) and the sieving coefficients of both the plasma
      separator (SCPS) and the plasma fractionator (SCPF): CC = CD/CP = SCPS.(1 -
      FFPF.SCPF)/(1 - FFPF) where CP is the albumin concentration of the patient's
      plasma. From the above relations, CS can be determined as follows: CS =
      CC.CCaimed.CP Because many kinds of proteins are removed during a single DFPP
      treatment, a slightly higher albumin concentration in the supplementation fluid
      is needed to maintain an appropriate plasma level. Therefore, the CR value should
      be more than unity. For a patient with hematocrit (HCT) of 30%, body weight (BW)
      of 50 kg, and CP of 3.0 g/dl, who is receiving a DFPP treatment using AP-05H
      (SCPS of 0.970) and Evaflux 2A (SCPF of 0.526) under FFPF of 0.8 with VS of 500
      ml, VP = BW(1- HCT/100)/13 = 50 x (1 - 30/100)/13 = 2.69 L, VR = 500/(2.69 x
      1,000) = 0.186, CC = 2.81, and CCaimed = 1.25 assuming 1.1 for CR. Therefore, CS
      = 2.81 x 1.25 x 3.0 = 10.5 g/dl using the above equations.

PMID- 10078303
TI  - Evaluation of methemoglobin formation during the storage of various hemoglobin
      solutions.
AB  - Many researchers are trying to develop a blood substitute based on chemically
      modified human hemoglobin. In the process of making such solutions, we were faced
      with the problem of determining the best storage conditions to minimize oxidation
      of the solutions between the time of manufacture and use. Samples of stroma-free
      hemoglobin, purified A0 hemoglobin, and various cross-linked hemoglobins were
      stored for 8-12 months at +4 degrees C -20 degrees C, and -80 degrees C and were
      analyzed periodically for formation of methemoglobin (MetHb). Various suspending
      solutions were evaluated for their effects on the rate of MetHb formation, and
      the approximate rates of MetHb production per month were calculated. Short-term
      storage of hemoglobin solutions (< 14 days) can be done at +4 degrees C, but
      extended storage should be done at -80 degrees C with quick thawing. Salts
      minimize the hemoglobin oxidation during the stress of freeze-thaw operations.
      Storage at -20 degrees C. presents further problems and should be avoided.

PMID- 10078304
TI  - Long-term implantation of a new implantable programmable insulin pump in two
      diabetic dogs.
AB  - A positive-pressure implantable programmable pump with an integrated sideport and
      a detachable catheter was tested for long-term intraperitoneal insulin delivery
      in 2 diabetic dogs. Programming and refilling of the pump was simple and
      presented no problems during 28 months of pump function. During pump therapy an
      acceptable degree of glycemic control was maintained. No catheter occlusion
      occurred, and no skin erosions or infections were observed. Insulin in the pump
      reservoir was stable. After 9.5 months of pump function, flow progressively
      decreased because of insulin precipitation in the valved accumulator.
      Solubilization of these precipitates using 0.1 N NaOH injected in the reservoir
      and drained through the sideport normalized pump delivery rates. We conclude that
      this device is safe for long-term intraperitoneal insulin delivery. The sideport
      enables discrimination between different causes of pump malfunction and allows
      for the safe use of an alkaline solution to remove insulin precipitates, thus
      avoiding pump explantation.

PMID- 10078305
TI  - Three different hepatocyte transplantation techniques for enzyme deficiency
      disease and acute hepatic failure.
AB  - The effects of three different techniques of hepatocyte transplantation were
      investigated: transplantation of free hepatocytes into the spleen and
      intraperitoneal transplantation of microcarrier-attached hepatocytes or of
      microencapsulated hepatocytes. The liver-supportive functions of these
      transplanted hepatocytes were analyzed using either the Gunn rat
      (hyperbilirubinemia) or rats with acute liver failure. In the Gunn rat
      intraperitoneal transplantation of microcarrier-attached hepatocytes resulted in
      a significant reduction of plasma bilirubin for 28 days whereas intraperitoneal
      transplantation of microencapsulated hepatocytes was ineffective notwithstanding
      immunosuppression by cyclosporin A. Intrasplenic hepatocyte transplantation was
      only effective in reducing plasma bilirubin for 14 days. During acute liver
      failure, liver support was achieved temporarily by hepatocyte transplantation in
      the spleen, by intraperitoneally transplanted microcarrier-attached hepatocytes,
      and by microencapsulated hepatocytes to equal extents, the microencapsulated
      hepatocytes being the least effective after 8 h of liver ischemia.

PMID- 10078306
TI  - Tissue reconstruction in primary cultured rat hepatocytes on asialoglycoprotein
      model polymer.
AB  - Adult rat hepatocytes attached on an asialoglycoprotein model polymer, poly-N-p
      vinylbenzyl-D-lactonamide (PVLA), formed anchored multilayer aggregates that had
      stable three-dimensional structure when epidermal growth factor (EGF) and insulin
      were added to the culture medium. The formation of multilayer aggregates depended
      on the concentrations of EGF and insulin added. Furthermore, the formation was
      synergistically accelerated by the presence of both hormones. Cells in the
      aggregates expressed a higher level of albumin secretion and lower proliferative
      ability than those in monolayer cultures on collagen. It seemed likely that the
      cells in multilayer aggregates experienced stable differentiated states
      resembling those in vivo through the formation of multilayer aggregates. The
      culture system described here has potential use for the study of the process of
      liver regeneration and the development of hepatic module systems such as a
      bioreactor and a hybrid artificial liver.

PMID- 10078307
TI  - Microcomputer-based automatic regulation of extracorporeal circulation: a trial
      for the application of fuzzy inference.
AB  - Since its establishment many researchers have been trying to automate the process
      of extracorporeal circulation (ECC). We developed a preliminary experimental
      model of an automatic regulatory system for ECC. The purpose of the system was to
      regulate basic hemodynamic parameters such as pump flow and withdrawal blood
      volume. It was divided into three main components: data sampling unit, central
      processing unit, and controlling unit. Based on this model we were able to
      achieve autoregulation of ECC using minimum configuration; however, the system
      lacked smoothness. This was partly because it was based on a "static" regulation
      system which used conditional statements having multiple parameters. In this
      study, we applied fuzzy logic to the former model to achieve more accurate and
      reliable regulation. We report experimental results for the new system and
      compare the data between clinical circulation in 13 infants (mean body weight,
      13.32 +/- 5.99 kg) and experimental regulation in 7 mongrel dogs (mean body
      weight, 11.9 +/- 2.53 kg). The comparative study revealed no statistical
      difference between the two groups. This result suggests that the automatic
      regulation of ECC may be an alternative to manual operation by a professional
      perfusionist in the near future.

PMID- 10078308
TI  - Pericardiovascular approach to cardiac assist: acute feasibility study.
AB  - We tested the hypothesis that external synchronized compression of the
      cardiovascular system can achieve effective hemodynamic assistance while
      circumventing problems associated with the blood-polymer interface in traditional
      cardiac assist devices. Ten dogs were studied to develop and test prototype
      devices and evaluate their hemodynamic effectiveness. Copulsation assistance was
      studied in animals with fibrillating hearts using Anstadt pericardiac cups. Mean
      systolic arterial pressure of 81.2 mm Hg and cardiac output of 2.9 L/min were
      achieved. Counterpulsation assistance was studied by inflating during diastole a
      balloon placed between the thoracic aorta and periaortic sheath and deflating the
      balloon during systole. In 4 dogs, 25 +/- 8.6% (SEM) of diastolic augmentation
      and 8.3 +/- 1.2% of systolic unloading were achieved. These preliminary results
      indicate the feasibility of a pericardiovascular approach to cardiac assistance.
      Further device development and the integration of copulsation and
      counterpulsation may improve cardiac output, reduce cardiac afterload, augment
      coronary perfusion, and ultimately benefit patients with severe heart failure.

PMID- 10078309
TI  - Belgian Biomed Study concerning transfusion for surgery.

PMID- 10078310
TI  - The Belgium BIOMED Study about transfusion for surgery.

PMID- 10078311
TI  - The meaning of grandparenthood: a critical review and research agenda.
AB  - Despite the importance of grandparenthood in the personal and family context, as
      well as its increasing economic, political and legal implications, research
      addressing its meaning and significance has been sparse and characterized by
      theoretical and methodological limitations. The main theoretical limitation is
      the lack of a clear definition at the conceptual level. Methodological
      limitations include not only the use of small and non-inclusive samples, most of
      which pertain to only one or two generations, but also the lack of a well
      developed multidimensional measurement approach. The aim of the present paper is
      to describe the status of research on the meaning of grandparenthood, and discuss
      its conceptual and methodological developments, especially regarding measurement
      issues. An example of an ongoing research program is provided as a guideline for
      future research.

PMID- 10078312
TI  - Associated physical disease in a demented population.
AB  - Clinical experience indicates that physical diseases are probably underdiagnosed
      in patients suffering from dementia. We investigated the prevalence of physical
      diseases in patients with different types of dementia by means of a retrospective
      patient record survey including 236 inpatients and outpatients referred for
      dementia evaluation to the Dementia Investigation Unit, University Hospital in
      Linkoping during 1994. Forty-four patients had dementia of the Alzheimer type, 78
      had vascular dementia, 28 had dementia due to multiple etiologies, 42 were not
      demented, and 44 patients could not be classified by the DSM IV criteria. The
      physical diseases were registered as separate diagnoses comprising all newly
      diagnosed physical diseases and previously known diseases that had exacerbated
      and contributed to the medical contact. Sixty-four percent of the patients had
      previously unknown physical diseases and/or exacerbation of previously known
      diseases. The most common physical conditions were cobalamin deficiency and
      infectious diseases, which occurred in 27% and 24% of the patients, respectively.
      There was no difference in the number or kinds of diagnoses between the
      diagnostic groups. Associated physical diseases were underdiagnosed in patients
      referred for dementia evaluation. We suggest that thorough medical investigation
      and adequate treatment are of importance in the management of dementia.

PMID- 10078313
TI  - Slow wave sleep (SWS) distribution across night sleep episode in the elderly.
AB  - Slow wave sleep (SWS) distribution across night sleep was shown to be different
      between infants and young adults. The present research aimed at studying the SWS
      distribution across night sleep in elderly subjects. Nine healthy elderly
      subjects, 61-71 years old, were submitted to nocturnal polygraphic sleep
      recording. Eleven young subjects, 21-23 years old, were the control group.
      Recordings were visually analyzed according to Rechtschaffen and Kales rules; the
      method proposed by Webb and Dreblow was used for scoring SWS. An NREM-REM cycle
      was defined as a sequence of NREM and REM sleep not interrupted by a waking
      period longer than 15 minutes. SWS percentage was calculated for each successive
      NREM episode. No significant association between SWS percentage and cycle rank
      was shown in elderly subjects, whereas a significant association was observed in
      the young ones. This kind of SWS distribution could be interpreted as reflecting
      the restructuring of internal organization of sleep in the elderly.

PMID- 10078314
TI  - Serum leptin and longevity.
AB  - There are changes in the ability to regulate energy balance and caloric intake
      with aging. Consequently, we investigated whether human aging modifies the levels
      of serum leptin, a novel hormone implicated in the regulation of energy balance.
      We studied 268 Caucasian men and women aged 22-85 years, and divided them into
      groups with mean ages of 30, 40, 50, 65, 75, 80 and 85 years. Fasting serum
      leptin concentrations were determined by radioimmunoassay. Subjects aged 65 or
      older were followed for five years after the blood sampling. There were no
      statistically significant differences in fasting serum leptin concentrations
      across different age groups in females (p = 0.090). Fasting serum leptin
      concentrations were also similar in different age groups in males, except that
      males in the 30-year age group had lower serum leptin levels than males in the 75
      year age group (p = 0.042). Leptin levels were 2-3 fold higher in females than in
      males in each age group (p < 0.005 except p = 0.063 in the 75-year age group).
      Elderly women, who lived longer, had 47% higher (p < 0.05) serum leptin
      concentrations, and 17% higher (p < 0.001) BMI than the women who died within
      five years of blood sampling. Leptin levels were not statistically different in
      these women after adjusting for BMI. Thus, aging has no apparent effect on serum
      leptin levels in women or men, and the gender differences in leptin is present
      also in the older age groups. Higher leptin concentrations in the females who
      live longer may reflect a better nutritional status, and a greater adipose tissue
      mass rather than a primary factor for survival.

PMID- 10078315
TI  - Age-dependent sensitization to oxidative stress by dietary fatty acids.
AB  - Experiments were designed to test the hypothesis that short-term feeding of a
      high polyunsaturated fatty acid (PUFA) diet would increase susceptibility to
      lipid peroxidation in an age-dependent manner. Young (6 month) and old (24 month)
      male B6C3F1 mice were fed modified AIN-76 diets containing either 5% corn oil
      (CO, N = 5 per age group) or 19% fish oil plus 1% corn oil (FO, N = 20 per age
      group) for two weeks. Five CO and five FO diet mice per age received an
      intraperitoneal injection of normal saline and were sacrificed one hour later;
      the remaining FO diet mice (N = 15 per age) were challenged with an acute
      systemic oxidative stress by intraperitoneal injection of 125 mg iron/kg body
      weight as iron dextran, and were sacrificed 1, 5, and 24 hours post-injection.
      Microsomal membrane fatty acid analysis revealed that increased age and a FO diet
      significantly increased membrane PUFA content. Serum iron levels increased
      significantly following iron treatment, peaking at 5 hours in both age groups.
      Formation of microsomal malondialdehyde (MDA), a product of lipid peroxidation,
      was significantly greater in the livers of the young mice. The temporal patterns
      of serum iron and microsomal MDA concentrations were significantly correlated in
      young mice, but not in old mice. Histochemical examination showed that liver iron
      accumulation following iron injection was similar in both age groups, but was
      associated with a significant temporal increase in liver apoptotic cells in young
      mice, but not in old mice. Thus, both age groups had similar iron exposure and
      iron accumulation, and the liver microsomal membranes of old mice were more
      unsaturated, yet there was significantly greater peroxidative damage (MDA
      formation) and cell death (apoptosis) in the young mouse livers. These findings
      suggest that the older animals have upregulated antioxidant defenses.

PMID- 10078316
TI  - Effects of caloric restriction or augmentation in adult rats: longevity and
      lesion biomarkers of aging.
AB  - Caloric restriction (CR) initiated in young rodents has been thoroughly
      documented to enhance longevity, but its efficacy when introduced at older ages
      has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1
      hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified
      NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented
      with corn oil and sweetened condensed milk (S). The C control rats were fed ad
      libitum, R rats were restricted to 32% of the caloric intake of the controls, and
      S rats were allowed to consume not more than 8% more calories than C rats. After
      6 weeks, the average weights were significantly different between all diet and
      age groups. Although calorie manipulation altered body weight, no significant
      effect of the dietary intervention on longevity was found. The average lesion
      burden, including tumor burden and prevalence of nearly all commonly occurring
      lesions, were comparable between the groups. Thus, the manipulation of weight at
      ages beyond middle age has a much less profound impact than similar interventions
      during growth and maturation in rats.

PMID- 10078317
TI  - The relationship of peripheral motor nerve conduction velocity to age-associated
      loss of grip strength.
AB  - Age-associated loss of muscle strength is attributed to decreasing muscle mass.
      Both strength and mass are dependent on peripheral innervation. However, the
      association between nerve function and age-associated strength loss has not been
      studied directly. The median nerve contribution to grip strength was estimated
      using nerve conduction velocity (NCV). Grip strength and NCV were measured in 197
      male participants of the Baltimore Longitudinal Study of Aging (age 59.0 +/- 13.9
      years). Multiple regression and path analyses were used separately to examine the
      association between median NCV and grip strength. Grip strength showed a negative
      quadratic relationship with increasing age (r2 = 0.32, p < 0.001) with a major
      change in slope occurring after 64.7 years of age. Median NCV (r2 = 0.14, p <
      0.001) declined linearly with age. Median NCV significantly contributed to grip
      strength (p < 0.001) while controlling for forearm muscle mass (forearm
      circumference), self-reported 24-hour caloric expenditures, and age. The median
      nerve has an independent contribution to age-associated levels of muscle
      strength. The level of the effect was smaller than what could be attributed to
      forearm muscle mass or age.

PMID- 10078318
TI  - A prospective study of acute illness in the nursing home.
AB  - Managing acute illness is an important aspect of medical care for nursing home
      residents, but little data is available on the nature of acute illness in this
      setting. The aims of this study were to determine the incidence, etiologies, risk
      factors and outcomes of acute illness in nursing home residents. This was a
      prospective cohort study of residents at one Veterans Administration nursing home
      (N = 140). Acute illness episodes were identified prospectively for one year
      through staff interviews and medical record review. Etiologies of acute illness
      were determined based on standardized criteria. Subjects were followed for three
      years to determine hospital utilization, discharge location and survival. There
      were 113 acute illness episodes identified (0.59 episodes per subject per month).
      The most common etiologies were pneumonia (33% of episodes), and urinary tract
      infection (27%). Significant risk factors for acute illness included anemia,
      dependence in mobility and surveillance time (i.e., duration of time monitored
      for illness episodes) in the nursing home (model chi 2 27.16, p < 0.001).
      Subjects who developed acute illness had increased hospital utilization during
      the first year of follow-up (p = 0.034); they were also less likely to be
      discharged home by both one year (chi 2 12.37, p < 0.001) and two years of follow
      up (chi 2 9.45, p = 0.009). When hospice and respite residents with short stay
      were excluded, subjects who developed acute illness had lower 3-year survival
      (Log rank 4.97, p = 0.026), and the rate of acute illness episodes (i.e., number
      per month monitored) predicted 3-year mortality (Cox proportional hazards, p <
      0.001). In conclusion, acute illness is extremely common among nursing home
      residents, and is most often due to infection. The occurrence of acute illness
      identifies residents who have increased hospital utilization, are less likely to
      return home, and have decreased long-term survival.

PMID- 10078319
TI  - Changes in nutritional status during the hospital stay: a predictor of long-term
      survival.
AB  - The objectives of this prospective observational study were to assess whether: 1)
      midarm circumference (MAC), previously shown to predict in-hospital mortality,
      maintains its prognostic implication after discharge; 2) in-hospital changes in
      aspecific indicators of the health status are predictors of long-term survival.
      The study population consisted of 249 patients from the general community [mean
      age 80 +/- 7 (70-99) years], consecutively discharged from geriatric and medical
      wards of an acute care hospital. Changes in health status during hospitalization
      were recorded (dynamic or delta variables) and health-related variables were
      collected at discharge (discharge variables). The relationship of both sets of
      variables to survival over a 3-year period was assessed by Cox's proportional
      hazards regression analysis. The discriminatory efficacy of predictive models was
      estimated by the Hanley and McNeil method. Survival curves were drawn with the
      patients alternatively grouped according to the presence or absence of each of
      the predictive variables. Serum albumin < 3.5 g/dL (hazard rate = 0.57, 95%
      confidence limits = 0.33-0.96) and dependency in at least one ADL (h.r. = 0.87,
      c.l. = 0.79-0.98) were found to be associated with increased mortality, and delta
      MAC (h.r. = 1.03, c.l. = 1.01-1.05), i.e., there was a positive change or no
      change in MAC from admission to discharge, with increased survival. A slightly
      weaker predictive model was obtained using only discharge variables. However,
      Hanley and McNeil's analysis showed that both models were far from achieving the
      optimal discrimination of high from low risk subjects. Effects on survival of
      individual variables varied in magnitude and dependency on time. We concluded
      that measuring in-hospital changes in nutritional status might improve prediction
      of long-term survival. Attempts should be made to identify variables having the
      strongest prognostic implications, and to tailor dynamic assessment to the needs
      of selected categories of patients.

PMID- 10078321
TI  - Close encounters of a new kind: toward an integration of psychoanalysis and
      Buddhism.

PMID- 10078320
TI  - Effect of aging on spontaneous and induced mouse testicular germ cell apoptosis.
AB  - The purpose of this study was to determine whether apoptotic cell death of mouse
      testicular germ cells varies with increased age, or with exposure to an acute
      systemic oxidative stress. Results show that the percent of seminiferous tubules
      with apoptotic cells, and the number of apoptotic cells/tubule cross section were
      not significantly altered with age. However, there were significantly more
      apoptotic metaphase spermatocytes at tubule stage XIV in 24-month-old mice than
      in 6-month-old mice. Oxidative stress significantly increased apoptotic metaphase
      spermatocytes in young mice, and severely reduced testicular apoptosis in old
      mice. Our results have potential clinical relevance to changes with increased age
      in human sperm aneuploidies.

PMID- 10078322
TI  - Horney, Zen, and the real self: theoretical and historical connections.

PMID- 10078323
TI  - Suffering and the dialectical self in Buddhism and relational psychoanalysis.

PMID- 10078324
TI  - A glimpse of Zen practice within the realm of countertransference.

PMID- 10078325
TI  - Buddhist meditation and countertransference: a case study.

PMID- 10078326
TI  - What on closer examination disappears.

PMID- 10078327
TI  - Words and wordlessness: a clinical approach to the difference.

PMID- 10078328
TI  - Creativity and psychoanalysis: annual Karen Horney Memorial Lecture, the
      Association for the Advancement of Psychoanalysis.

PMID- 10078329
TI  - Plasma amino acid levels after carbon tetrachloride induced acute liver damage. A
      dose-response and time-response study in rats.
AB  - The aims of the present study were to assess the changes of individual plasma
      amino acid levels in relation (1) to the severity of liver damage and (2) to the
      process of liver recovery. Acute liver injury was induced by an intragastric
      administration of CCl4 diluted in olive oil in doses of 2, 4 and/or 6 g of CCl4
      per kg b.w. The control rats received olive oil only. Animals were sacrificed at
      16, 24, 48 and 96 hours after treatment. The severity of liver injury was
      assessed by histological examination, by changes in ALT and AST in the blood
      plasma and by changes in liver weight. Statistical analysis was carried by ANOVA,
      p < 0.05 was considered significant. The Spearman rank correlation coefficient
      was used as a measure of the degree of linear relationship between variable and
      dose. In the period of the development of acute liver damage, i.e. at 16 and 24
      hours after treatment, an increase in blood plasma amino acid levels and positive
      correlations with the dose of CCl4 were observed for most individual amino acids.
      The only exception was arginine which decreased in a dose dependent manner. At a
      phase of liver recovery, i.e. at 48 and 96 hours after CCl4 treatment, the
      concentrations of some individual amino acids decreased below the control values.
      The negative correlation with the dose of CCl4 occurred for taurine and
      isoleucine (at 48 hours) and taurine, threonine, valine, methionine, isoleucine
      and leucine (at 96 hours).

PMID- 10078330
TI  - Determination of the protooncogene ets-2 gene transcript in human brain at the
      atto-gram-level by the use of competitive RT/PCR.
AB  - Protooncogenes (PO) play a crucial role for brain biology and pathology. Only the
      concerted action of protooncogenes enables normal brain development. The reliable
      and sensitive quantification of brain PO is still holding centre stage in
      neurobiological research. The aim of our study was therefore the determination of
      PO in minute amounts of brain areas. For this purpose we decided to apply the
      most sensitive detection principle of competitive reverse transcriptase
      polymerase chain reaction using capillary electrophoresis and laser-induced
      fluorescence detection. We selected the PO ets-2 for our studies as this
      transcription factor was shown to be involved in neurodegenerative disease. As
      little as 10 ng of total RNA each were extracted from 5 different regions of
      human postmortem brain and used in the assay system. Our results revealed that
      the ets-2 gene transcript was detectable at the atto-gram level in the brain
      (54.5 +/- 17.7 ag/ 10 ng RNA in the occipital lobe, 34.2 +/- 7.5 in temporal
      lobe, 40.2 +/- 15.6 in the frontal lobe, 31.4 +/- 15.7 in the cerebellum, and
      undetectably low in the parietal lobe). This is the first report at this
      sensitivity level providing neurobiology with a powerful analytical tool.

PMID- 10078331
TI  - Unusual amino acids. VIII. Asymmetric hydrogenation of some heteroaryl-N-Cbz and
      N-Boc aminocinnamic acid derivatives.
AB  - (Z)-alpha-[(Benzyloxy)- or (tert.-butyloxy)carbonylamino]-beta (thienyl)- or
      (furyl)-acrylic acids and their esters were prepared by known methods and
      hydrogenated to the corresponding optically active alanine derivatives with
      optical yields in the range of 58-93% ee using the cationic rhodium complex of
      "PROPRAPHOS".

PMID- 10078332
TI  - Contribution of serum albumin to the transport of orally administered L
      tryptophan into liver of rats with L-tryptophan depletion.
AB  - The role of serum albumin in the transport of orally administered L-tryptophan
      (Trp) into rat tissues was examined using analbuminemic and Sprague-Dawley (SD)
      rats with and without alpha-methyl-DL-tryptophan (AMT)-induced Trp depletion. Trp
      was orally administered to rats 16 h after AMT or 0.85% NaCl administration, when
      liver tryptophan 2,3-dioxygenase and protein synthetic activities in AMT-treated
      rats were similar to those of 0.85% NaCl-treated rats. After oral Trp
      administration, regardless of the presence or absence of Trp depletion, free
      serum Trp concentrations were similar in the analbuminemic and SD rats, while
      total serum Trp concentrations were lower in analbuminemic rats than in SD rats.
      Although liver, brain, and muscle Trp concentrations after oral Trp
      administration under Trp depletion were lower in analbuminemic rats than in SD
      rats, the ratio of the liver Trp concentration in analbuminemic rats to that in
      SD rats was smaller than that of the brain or muscle Trp concentration. These
      results suggest that variations in serum albumin levels could affect the
      transport of orally administered Trp into the liver of rats with Trp depletion.

PMID- 10078333
TI  - Fatty acids and glycerol or lactate are required to induce gluconeogenesis from
      alanine in isolated rabbit renal cortical tubules.
AB  - In isolated rabbit renal cortical tubules, glucose synthesis from 1 mM alanine is
      negligible, while the amino acid is metabolized to glutamine and glutamate. The
      addition of 0.5 mM octanoate plus 2 mM glycerol induces incorporation of [U
      14C]alanine into glucose and decreases glutamine synthesis, whereas oleate and
      palmitate in the presence of glycerol are less potent than octanoate.
      Gluconeogenesis is also significantly accelerated when glycerol is substituted by
      lactate. In view of an increase in 14CO2 fixation and elevation of both cytosolic
      and mitochondrial NADH/NAD+ ratios, the activation of glucose formation from
      alanine upon the addition of glycerol and octanoate is likely due to (i)
      stimulation of pyruvate carboxylation, (ii) increased availability of NADH for
      glyceraldehyde-3-phosphate dehydrogenase and (iii) elevation of mitochondrial
      redox state causing a diminished provision of ammonium for glutamine synthesis.
      The induction of gluconeogenesis in the presence of alanine, glycerol and
      octanoate is not related to cell volume changes. The results presented in this
      paper show the importance of free fatty acids and glycerol for regulation of
      renal gluconeogenesis from alanine. The possible physiological significance of
      the data is discussed.

PMID- 10078334
TI  - Terfenadine induces toxicity in cultured cerebellar neurons: a role for glutamate
      receptors.
AB  - Exposure of cultured cerebellar neurons to the histamine H1 receptor antagonist
      terfenadine resulted in neuronal degeneration and death. Terfenadine
      neurotoxicity was dependent upon concentration and time of exposure. After 2 h
      exposure, 20 microM terfenadine reduced the number of surviving neurons by 75%,
      and as low as 10 nM terfenadine induced significant neurotoxicity after 5 days of
      exposure. Neuronal sensitivity to terfenadine changed with age in culture, and at
      25 days in culture neurons appeared to be much less sensitive than at 5 or 9-17
      days in culture. Neurotoxicity by terfenadine could not be prevented by high
      concentrations of histamine (5 mM), but it was significantly delayed by blocking
      NMDA or non-NMDA glutamate receptors with MK-801 or CNQX respectively, suggesting
      the involvement of excitatory transmission mediated by glutamate in the
      neurotoxicity induced by terfenadine in these neurons. We also found that the
      presence of terfenadine (5 microM) unveiled the potential excitotoxity of the non
      NMDA receptor agonist AMPA (100 microM), and reduced the concentration of
      glutamate necessary to induce excitotoxicity, compared to untreated cultures.
      These results suggest a role for terfenadine in the modulation of the excitotoxic
      response mediated in cerebellar neurons through ionotropic glutamate receptors.

PMID- 10078335
TI  - Changes in plasma taurine levels after different endurance events.
AB  - The sulphonated amino acid taurine increased significantly in the plasma of
      trained athletes after three endurance exercises of different duration and
      intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a
      Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such
      results indicated that the speed at which the exercise is performed, referred to
      as the intensity, rather than the duration of the exercise, correlated with the
      elevated taurine levels possibly indicating its release from muscle fibres. The
      plasma amino acid pool decreased significantly in relationship with the duration
      of the exercise, caused by their utilisation for glucogenesis. The possible
      sources of the increased plasma taurine are discussed.

PMID- 10078336
TI  - Substituted 4-hydroxyproline di- and tri-peptides as cytotoxic agents.
AB  - 4-Hydroxyproline di- and tri-peptides and N-cbz-hydroxypropyl- glycinamides were
      observed to be potent cytotoxic agents against the growth of suspended single
      cells, L-1210, Tmolt3, and HeLa-S3. The agents were not as potent against the
      growth of cultured solid tumor cells. Selected derivatives were investigated for
      their mode of action in Tmolt3 leukemia cells. The compounds selectively
      inhibited DNA synthesis at 50 and 100 microM. The target site of action of the
      agents appeared to be the purine de novo pathway with marked inhibition of the
      activities of the two regulatory enzymes of the pathway, i.e. PRPP amido
      transferase and IMP dehydrogenase. d[NTP] pools were reduced by the agents
      consistent with their overall reduction of DNA synthesis. Other marginally
      inhibited targets of the agents were r-RNA polymerase and TMP-kinase activities.
      The DNA molecule itself did not appear to be a target of these agents.

PMID- 10078337
TI  - Structural organization of the human eukaryotic initiation factor 5A precursor
      and its site-directed variant Lys50-->Arg.
AB  - The molecular properties of the human eukaryotic initiation factor 5A precursor
      and its site directed Lys50-->Arg variant have been investigated and compared.
      Structure perturbation methods were used to gain information about the protein
      architecture in solution. Intrinsic and extrinsic spectroscopic probes
      strategically located in the protein matrix detected the independent unfolding of
      two molecular regions. Three cysteines out of four were titrated in the native
      protein and the peculiar presence of a tyrosinate band at neutral pH was
      detected. At alkaline pH only two tyrosines out of three were titratable in the
      native protein, with an apparent pK of about 9.9. Native protein and its Lys50-
      >Arg variant reacted in a similar fashion to guanidine and to pH variation, but
      differently to thermal stress. The complex thermal unfolding of both proteins
      indicated the presence of intermediates. Spectroscopic data showed that these
      intermediates are differently structured. Consequently, the two proteins seem to
      have different unfolding pathways.

PMID- 10078338
TI  - [Hypertrophic cardiomyopathy and physiologic hypertrophy in athletes: a new
      diagnostic approach using tissue color Doppler].

PMID- 10078339
TI  - [Distinguishing between physiologic hypertrophy in athletes and primary
      hypertrophic cardiomyopathies. Importance of tissue color Doppler].
AB  - In order to assess the value of Doppler tissue imaging (DTI) in the
      differentiation of physiological hypertrophy of athletes from primary
      hypertrophic cardiomyopathy (HCM), the authors compared a group of 20 normal, non
      athletic subjects, a group of 43 competitive athletes and a group of 20 patients
      with mild HCM. In addition to the conventional echocardiographic criteria, the
      velocity of wall motion at the endocardium and epicardium of the interventricular
      septum and the posterior wall as well as their gradients, were measured
      throughout the cardiac cycle. No significant difference was observed between
      normal subjects and the athletes with respect to velocities and the gradients of
      velocity. Early diastolic velocities of the posterior wall and interventricular
      septum were significantly lower than those of normal subjects and athletes. The
      systolic and early diastolic gradients of velocity of the posterior wall were
      significantly lower in HCM compared with the normal subjects and athletes. The
      gradient of velocity between the endocardium and epicardium of the
      interventricular septum was significantly lower in HCM compared with normal
      subjects in early diastole and with athletes in systole and early diastole. The
      best Doppler tissue imaging parameter to differentiate pathological hypertrophy
      of HCM from physiological hypertrophy of athletes was analysis of the gradient of
      velocity in early diastole of the posterior wall. A value of 0.7 sec-1
      differentiated HCM with a sensitivity of 89%, a specificity of 95% and a
      diagnostic accuracy of 94%. Doppler tissue imaging is a more sensitive and
      specific technique than conventional Doppler echocardiography for detecting
      moderate forms of HCM.

PMID- 10078340
TI  - [Evaluation of a clinical and scintigraphic management strategy for cardiac risk
      before abdominal aorta surgery. Apropos of 982 surgical patients].
AB  - The incidence of major cardiac events (death, infarction) is over 5% after
      programmed aortic vascular surgery. The aim of this study was to evaluate a
      management strategy of this risk based on the clinical status and targeted
      indication of myocardial scintigraphy, coronary angiography and myocardial
      revascularisation. A first phase (1991-1993, 451 patients) confirmed the
      prognostic value of clinical (age, previous cardiac history, diabetes,
      hypertension, electrocardiogrammes) and scintigraphic features: the cardiac
      mortality was 1.25% in patients with a low clinical risk (70.3% of cases) and
      4.5% in patients with a high clinical risk (2 factors, 29.3% of cases) (p <
      0.01). In the latter group, the mortality was zero after normal myocardial
      scintigraphy and 7.2% after abnormal myocardial scintigraphy (p < 0.01) and 12.5%
      in cases with reversible defects (p < 0.01). During the second phase of the study
      (1994-1997, 531 patients) coronary angiography was performed in patients with a
      high clinical risk and abnormal scintigraphy (10.9% of cases). This led to a
      myocardial revascularisation in 3.6% of patients. The cardiac mortality was then
      the same in the low and high a priori clinical risk: 2.3 and 2.8% (NS). The use
      of simple clinical criteria enables surgery in the majority of candidates for
      aortic vascular surgery, scintigraphy being reserved for about one patient in ten
      with myocardial revascularisation in less than 4% of cases. The operative cardiac
      mortality then decreases to under 2.5%.

PMID- 10078341
TI  - [Diabetic coronary disease and risk of myocardial infarction].
AB  - The raised incidence of myocardial infarction and sudden death in diabetics was
      explained over 20 years ago by the increase in prevalence and severity of
      coronary atherosclerosis. Coronary angiographies of 820 consecutive patients
      admitted to hospital for coronary artery disease were analysed. One hundred and
      fifteen of these patients (14%) were diabetic. In 77.4% of diabetics and 72.6% of
      non-diabetics, coronary angiography showed coronary lesions which were usually
      distal and three vessel in diabetics. When the three coronary arteries were
      analysed globally, the percentage of patients with at least one mild stenosis was
      much higher in diabetics than in non-diabetics (50.6% vs 30.3% respectively, p <
      0.001), but there was no statistical difference in the number of severe stenoses
      or occlusions. The increase in mild stenosis in the diabetic population could
      indicate an anatomical predisposition to future rupture of a plaque. This result
      could explain the increased frequency of myocardial infarction and sudden death
      in diabetes, not necessarily preceded clinically by angina pectoris.

PMID- 10078342
TI  - [Prospective study on the mechanism of myocardial infarction without significant
      coronary stenosis].
AB  - The aim of this study was to evaluate prospectively the respective roles of the
      atheromatous plaque, coronary spasm and abnormalities of haemostasis in patients
      with myocardial infarction with normal coronary arteries. The study population
      included 25 patients (19 men and 6 women) with a mean age of 52.1 +/- 11.1 years
      (34-76 years). The diagnosis of myocardial infarction was made as the finding of
      2 out of 3 WHO criteria. It occurred spontaneously and was transmural in 80% of
      cases, inferior wall infarction in 9 patients (36%), anterior in 12 (48%) and
      lateral in 4 patients (16%). All patients underwent investigation on average 10
      days after infarction (1-42 days) by coronary angiography with quantitative
      angiography, endocoronary ultrasonography, an ergometrine provocation test for
      coronary spasm and a blood coagulation study. Coronary angiography was normal in
      4 patients but showed wall changes without stenosis > 50% in 20 patients and one
      case of aneurysmal arterial disease. Intracoronary thrombosis was detected in 6
      cases. Endocoronary ultrasonography confirmed the normality of the coronary
      arteries in 2 cases and showed atheroma in 23 cases (soft atheroma: n = 17 and
      hard: n = 6). It detected 66% of the coronary thrombi observed at angiography and
      found 3 other cases. Coronary spasm was verified in 10 patients (40%). The
      coagulation study was normal in 19 patients and showed increase in Pai-1 in 5
      patients and primary thrombocythemia in one case. The authors conclude that
      coronary angiographic data is less accurate than endo-coronary ultrasonography
      which best shows the extent and, above all, the nature of the plaques present in
      23 of the cases (92%). Coronary spasm may be a contributing factor in 40% of
      cases, in situ thrombosis in 36% of cases despite usually normal blood clotting
      studies. None of these abnormalities was observed in one case. The embolic cause
      of infarction was certain in 2 cases.

PMID- 10078343
TI  - [Importance of dual isotope myocardial tomoscintigraphy in the detection of
      coronary disease in the graft among 96 heart transplant recipients].
AB  - With a survival rate of 70% at 3 years, cardiac transplantation is the best
      treatment for end-stage heart disease. However, progressive development of graft
      atherosclerosis is frequent. Diagnosis of transplant coronary disease remains
      difficult and non-invasive tests have proved relatively insensitive. Therefore,
      coronary angiography performed annually is still the gold-standard test for the
      detection of heart transplant vasculopathy. We analyzed the records of 96
      patients (82 men and 14 women) who were transplanted from 1986 to 1996. Mean age
      was 53 +/- 2.7 and time elapsed from transplantation was mean 5.3 +/- 10 years.
      All patients had rest myocardial TI 201 perfusion SPECT, followed by MIBI gated
      SPECT after exercise. MIBI gated SPECT allows simultaneous evaluation of
      perfusion, regional LV function and global ejection fraction.
      Angiocoronarography, performed in all patients during the six months following
      radionuclide investigation, showed the presence of coronary heart vasculopathy in
      nine (9.3%). Seven of these patients had abnormal dual isotope imaging and 2 of
      them had normal perfusion but altered LV regional function. Sensitivity of dual
      isotope scintigraphy was 77% and specificity was 97.7%. Dual isotope scintigraphy
      is helpful to detect coronary vasculopathy in heart transplant recipients and may
      reduce indications of angiocoronarography.

PMID- 10078344
TI  - [Recommendation of the French Cardiology Society concerning diagnostic and
      interventional electrophysiology, permanent cardiac pacing and implantable
      automatic defibrillation].

PMID- 10078345
TI  - [Myocardial infarction caused by septic embolism during mitral endocarditis].
AB  - Embolic infarction is a rare complication of mitral valve endocarditis. The
      authors present the case of a patient with a linear vegetation of the anterior
      mitral leaflet measuring over 15 mm and entering the aortic valve orifice at each
      systole. This valvular infarction was the cause of an extensive anterior wall
      infarct treated by primary angioplasty because of haemodynamic instability. The
      outcome at 3 months was very favourable with regards to the mitral valve.
      However, a large mycotic coronary aneurysm developed at the site of angioplasty
      and there were sequellae of a large anterior wall infarction.

PMID- 10078346
TI  - [Rupture of a branch of the pulmonary artery during Swan-Ganz catheterization.
      Treatment by coil embolization].
AB  - Rupture of the pulmonary artery or of one of its branches during a Swan-Ganz
      catheterisation is a rare complication which remains lethal in about 50% of
      cases. The risk factors and mechanisms of this complication have been previously
      described. There are two means of treatment: intensive care and specific medical
      or surgical treatment. In this case, the rupture of the pulmonary artery occurred
      during Swan-Ganz catheterisation and was treated by coil embolisation. This
      simple and rapid technique seems to be very promising.

PMID- 10078347
TI  - [Complete atrioventricular block during temporal lobe epilepsy. Apropos of a
      case].
AB  - The authors report the case of a 37 years old woman with no previous medical
      history, admitted to hospital for investigation of unexplained syncope, sometimes
      associated with generalised fits. After standard non-invasive cardiovascular
      investigations, no diagnosis could be made. The tilt test induced a minor
      syncopal episode without reproducing the clinical symptoms. In view of the
      discordance between the induced and spontaneous symptoms, a neurological opinion
      was requested. During the recording of an electroencephalogram, syncopal
      atrioventricular block was observed, preceded by auditory hallucinations,
      reproducing exactly the clinical symptoms. Analysis of the sequence of events
      showed the conduction defect to arise after the onset of the epileptic fit,
      indicating a diagnosis of syncopal complete atrioventricular block complicating
      cryptogenic temporal epilepsy, and requiring specific treatment. This case
      illustrates the importance of close collaboration between cardiologists and
      neurologists in the management of cases of unexplained syncope.

PMID- 10078348
TI  - [Severe hemolysis complicated by renal insufficiency in a patient with mitro
      aortic bioprostheses and review of the literature].
AB  - The authors report a very rare case of massive haemolytic anaemia complicated by
      renal failure in a patient with a double aortic and mitral bioprosthesis. The
      haemolysis was attributed to degeneration of the aortic bioprosthesis causing
      turbulent flow, aggravated by associated infectious endocarditis. The essential
      condition for haemolysis is a change in blood flow through the valve by
      degeneration or other associated pathology. The haemolytic anaemia completely
      regressed after aortic valve replacement as did the renal failure.

PMID- 10078350
TI  - Standards Australia challenged on animal ID.

PMID- 10078349
TI  - [Severe flecainide acetate poisoning. Apropos of a case].
AB  - Poisoning with flecainide acetate is rare and associated with a high mortality.
      This usually occurs after massive ingestion but can also be observed during
      therapeutic overdose in patients with renal failure or with amiodarone therapy.
      The prognostic depends on the haemodynamic and rhythmic effects of the overdose
      one sign of which is widening of the QRS complexes. Major sodium bicarbonate or
      lactate infusion is the generally prescribed treatment. The authors report one
      case of a patient with renal failure on amiodarone who survived a severe
      flecainide acetate overdose.

PMID- 10078351
TI  - AVA needs to decide the best location to service members--and influence
      government policy.

PMID- 10078352
TI  - Magnetic resonance imaging and ultrasonography of the lumbricale muscles in the
      horse.

PMID- 10078353
TI  - Osteochondrodysplasia in Scottish Fold cats.
AB  - OBJECTIVE: To better characterise the bone and joint problems which can develop
      in Scottish Fold cats. DESIGN: Retrospective study of cases seen in five
      veterinary clinics and radiographic survey of cats in a cattery. RESULTS: Six
      Scottish Fold cats (four castrated males, two spayed females) aged between 5
      months and 6 years were presented for signs of skeletal disease including
      lameness, reluctance to jump, a stiff stilted gait, short misshapen distal limbs,
      swelling of plantar tarsometatarsal regions and short thick inflexible tails. A
      further four cases (one male, three females, 15 months to 11 years) were
      identified by radiographic screening of a cattery. A diagnosis of
      osteochondrodysplasia was based on characteristic radiological findings including
      irregularity in the size and shape of tarsal, carpal, metatarsal and metacarpal
      bones, phalanges and caudal vertebrae, narrowed joint spaces, and progressive new
      bone formation around joints of distal limbs with diffuse osteopenia of adjacent
      bone. A plantar exostosis caudal to the calcaneus was present in advanced cases.
      In all nine cases where pedigree information was available, affected cats
      allegedly originated from the mating of a Scottish Fold to a cat with normal
      ears. The severity and time of onset of physical signs, and rate of progression
      and extent of radiographic abnormalities, varied from case to case. Limited
      histological observations suggested the underlying problem may be an
      osteochondrodysplasia, related to inadequate cartilage maturation. Clinical signs
      were ameliorated by administration of pentosan subcutaneously in two of three
      cats in which it was trailed, and one of these also benefited from an oral
      glycosaminoglycan preparation. CONCLUSIONS: Clinical and radiological findings
      were ascribed to defective maturation and function of cartilage, particularly in
      the distal limbs, ears and tail. As all Scottish Fold cats suffered from
      osteochondrodysplasia of some degree, the best solution would be to avoid using
      fold-eared cats for breeding and instead use Scottish shorthairs.

PMID- 10078354
TI  - Acute collapse in a cat.

PMID- 10078355
TI  - Nasopharyngeal obstruction due to cystic Rathke's clefts in two dogs.

PMID- 10078356
TI  - Hypertrophic osteopathy and pneumonia in a macropod.

PMID- 10078357
TI  - Arterially perfused eye model of uveitis.
AB  - OBJECTIVE: To develop an in vitro model of uveitis based on an ex situ perfused
      eye to evaluate the anti-inflammatory activity of new pharmacological products.
      PROCEDURE: Eyes were removed from more than 60 dogs and 9 horses immediately
      after euthanasia and perfused with nutrient medium through the lateral long
      ciliary artery. Perfused eyes produced aqueous humour, and perfusion pressure was
      adjusted to obtain an intraocular pressure in the physiological range. When the
      eyes were treated with histamine, a complement C5a analogue peptide and hydrogen
      peroxide, typical signs of uveitis were produced. These included miosis, vascular
      leakage, reduced intraocular pressure, reduced flow of perfusate and, in some
      eyes, conjunctival oedema. RESULTS: Canine eyes showed a decrease in intraocular
      pressure and a decrease in perfusate flow rate when challenged with 100 mumol/L
      hydrogen peroxide. Flunixin meglumine (5 mumol/L), ketoprofen (5 mumol/L),
      indomethacin (5 mumol/L) as well as a new drug pirfenidone (10 mumol/L) prevented
      changes in intraocular pressure induced by hydrogen peroxide, but did not
      significantly moderate the mediator-induced changes in perfusate flow.
      CONCLUSIONS: This model is suitable for evaluating potential anti-inflammatory
      activity of drugs without having to induce uveitis in an experimental animal. The
      technique is suitable for species that range in size from cats to horses.

PMID- 10078358
TI  - A longitudinal study of racing thoroughbreds: performance during the first years
      of racing.
AB  - OBJECTIVES: To develop a profile of the racing careers of Thoroughbred horses in
      south-eastern Queensland, and to examine factors that affect racing during the
      first years of racing. DESIGN AND PROCEDURE: A longitudinal study using the
      racing records of a defined cohort of Thoroughbred horses that were born on or
      within 12 months following 1 August 1991. Data collection commenced in 1996 and
      will continue until all horses cease racing. In this paper two measures of
      performance were examined: race earnings during the first year of racing and
      cumulative proportion of horses still racing up to 2 years after their first
      start. Univariable and multivariable methods were used to describe and identify
      factors associated with the performance of these horses. RESULTS: By 31 July
      1997, 1804 horses were enrolled in the study including 916, 701, 152 and 35
      horses that first raced at 2, 3, 4 and 5 years of age, respectively. During their
      first year of racing, half the horses earned no more than A$450 from race
      earnings, and 710 (39.4%) horses earned no money at all. In comparison to poorly
      performing horses, well-performing horses were more likely to be male, to have
      started as 2-year-olds and to have had more starts during this year. Of the
      horses that first started as 2 and 3-year-olds, only 71 and 46% continued racing
      for at least 1 and 2 years after their first start, respectively. Length of
      racing life was associated with performance during the first year of racing
      (number of starts and average earnings per race), and with sex, date of birth and
      age at first start. CONCLUSIONS: The study confirmed a high wastage among racing
      Thoroughbreds. As expected, premature retirement from racing was linked to poor
      performance. During the first year of racing, the race earnings of an estimated
      1567 (86.9%) horses were insufficient to cover training costs. The 2-year-old
      racing cohort outperformed the older racing cohorts in each of the performance
      measures under investigation. Interpretation of this result, and the long-term
      effects of 2-year-old racing, was limited by the problem of confounding.

PMID- 10078359
TI  - Evaluation of diagnostic tests for Johne's disease in young cattle.
AB  - OBJECTIVE: To investigate the development of immune responses in calves
      experimentally and naturally infected with Mycobacterium paratuberculosis and to
      evaluate the potential for diagnostic tests to detect infected calves. DESIGN:
      Sequential testing of four treatment groups of calves over a 2 year period.
      PROCEDURE: Twenty-nine calves were allocated to four groups. Group D calves were
      orally dosed with M paratuberculosis, group N calves naturally exposed to M
      paratuberculosis, group V calves vaccinated for M paratuberculosis, and group C
      were control calves (not infected or vaccinated). Blood and faecal specimens were
      collected from each calf at monthly intervals to 18 months of age and then every
      2 months until they were slaughtered between the ages of 21 and 29 months.
      Specimens were tested using absorbed EIA, IFN-gamma EIA and faecal culture. The
      infection status of the calves was confirmed by extensive histopathological
      examination and tissue culture. RESULTS: M paratuberculosis infection was
      confirmed in 10 calves, comprising six of eight orally dosed calves, three of
      five naturally exposed calves and one of nine vaccinated calves. The six
      artificially infected calves and one naturally infected calf were detected
      shedding M paratuberculosis in their faeces. Results with positive absorbed EIA
      were obtained from one artificially infected calf, one naturally infected calf
      and three vaccinated calves. All calves including controls had positive results
      on at least one occasion using the IFN-gamma EIA. In addition, seven calves had
      positive bovine tuberculosis results using the IFN-gamma EIA, even though bovine
      tuberculosis has been eradicated from Australia. CONCLUSION: Detection of M
      paratuberculosis infection in young cattle continues to be difficult using
      current tests.

PMID- 10078360
TI  - Attempted infection of mice, rats and chickens by porcine strains of Lawsonia
      intracellularis.

PMID- 10078361
TI  - Vets gain significant backing in Victorian court decision.

PMID- 10078363
TI  - Native animal hypocrisy!

PMID- 10078362
TI  - Tail-docking legends.

PMID- 10078364
TI  - [Andre Dodin (1926-1995): the military school years].

PMID- 10078365
TI  - [Andre Dodin in Madagascar, 1953-1968].

PMID- 10078366
TI  - [Andre Dodin at the Institute Pasteur in Paris].

PMID- 10078367
TI  - [Letters in honor of Andre Dodin].

PMID- 10078370
TI  - [Ephemerides by Andre Dodin, secretary general of the Societe de pathologie
      exotique from 1975 to 1995. Facsimiles of the originals].

PMID- 10078372
TI  - [Articles by A. Dodin published in the Bulletin de la Societe de Pathologie
      Exotique].

PMID- 10078373
TI  - [Culture, environment and fecal hazards: anthropological observations].
AB  - This paper was presented as a tribute to Andre Dodin, formerly director of the
      Paris Pasteur Institute's cholera department. It was intended to: - recall
      representations of what is seen as pure, impure, sullied, dirty ... medical and
      social interventions depend not only on scientific theories but also on
      unconscious presuppositions linked to their particular history and culture; - to
      stress the necessity of reexamining epidemiological chains in fecal peril bearing
      in mind bodily techniques and the material and symbolic behaviour of the
      populations concerned; - to insist upon the fact that traditional sanitation
      techniques do exist and should not be neglected, whether it be to make use of
      them, avoid or combat them. It is not a question of idealizing local culture, but
      of becoming acquainted with it so as better to appreciate its role.

PMID- 10078374
TI  - [The role of bacterial diarrhea in developing countries].
AB  - Bacterial diarrheas in developing countries remain a major public health problem.
      Cholera is endemo-endemic since 1970. Clusters of Shigella infections are
      commonly observed during the rainy season. Other enteropathogen cause nosocomial
      infections and foodborne diseases. The HIV epidemic determined the emergence of a
      new trend of enteric diseases caused by opportunistic bacteria such as Salmonella
      Enteritidis, S. Typhimurium. The risk factors associated with these infections
      remains almost unknown. Treatment failure is related to an incre of high level
      resistance strains.

PMID- 10078375
TI  - [Cholera in Africa and in Latin America].

PMID- 10078376
TI  - [Djibouti, history of 2 epidemics of cholera: 1993-1994].
AB  - When two cholera epidemics broke out in Djibouti, respectively in 1993 and 1994,
      Bioforce was obliged to intervene. The first time, three goals were pursued:
      setting up a rehydration centre in a tent, organizing epidemiological
      surveillance and training local personnel in treatment and diagnosis techniques.
      The next year, the epidemic followed serious flooding. The epidemiological
      analysis showed that cholera had become endemic in the poor neighbourhoods of the
      town and that epidemic break-outs were favoured by contaminated surface water and
      disturbances in the distribution of drinking water. The epidemic of 1997,
      likewise following flooding, only confirmed this point of view.

PMID- 10078377
TI  - [The current status of research on a cholera vaccine].
AB  - Cholera remains today a major health problem in most developing countries. The
      long-term control of cholera depends on the improvement of hygiene but this is a
      distant goal for many countries. The availability of an effective cholera vaccine
      is thus important for the prevention of cholera in such countries. More than a
      century after the first attempt to vaccinate against cholera by Ferran in Spain,
      there is still no truly effective cholera vaccine. A bacterial fraction vaccine,
      referred to as CH1 +2 was prepared by Professor A. Dodin. A field trial of this
      vaccine was carried out in Zaire in 1983. Significant protection was observed but
      this vaccine was not evaluated in additional trials. Two other oral cholera
      vaccines, developed in Sweden and in the USA, were widely experimented on human
      beings: a combination of cholera toxin B-subunit and inactivated bacterial cells,
      and a live attenuated vaccine containing the genetically manipulated Vibrio
      cholerae O1 strain CVD 103-HgR. Despite their efficiency as evaluated in field
      trials (inactivated vaccine) or on volunteers (live vaccine), these vaccines have
      drawbacks that may limit their usefulness as practical vaccines. Protection
      induced by the inactivated vaccine was transient in young children, lasting only
      approximately for six months. One of the safety concerns associated with live
      vaccines is a possible reversion to virulence. Efforts should be continued to
      find a better cholera vaccine. A new vaccine development program based upon the
      hypothesis that immunoglobulin G directed to the O-specific polysaccharide of
      Vibrio cholerae O1 could confer protective immunity to cholera. This program may
      lead to the development of a cholera conjugate vaccine to elicit protection in
      infants.

PMID- 10078378
TI  - [Parasitic diseases and fecal hazards: diseases due to helminths].
AB  - Ascaris, trichocephalus, hookworm, necator and anguillula--all of which are human
      parasites--are closely linked to fecal peril and especially prevalent among
      populations in developing countries, where fecal hygiene is insufficient or
      lacking. Epidemiological surveys seeking to evaluate the frequency of the various
      intestinal helminths are usually intermittent, few in number, and especially
      difficult to compare because of the different coprological techniques used.
      However this may be, the respective prevalence of these worms depends on
      geographical, climatic, economic, and human conditions. Their effect on health is
      not negligible, especially on children's health and in particular when
      malnutrition also occurs. To fight effectively against these verminoses,
      education and economic development must be promoted, but the present situation of
      the economy in most developing countries is postponing indefinitely the fight
      against fecal peril especially as its control is not seen as a priority.

PMID- 10078379
TI  - [Intestinal parasitic diseases in an urban environment in Sahel. A study in a
      district of Niamey, Niger].
AB  - Health and environment in Niamey, a capital in Sahel, are particularly linked
      owing to population growth, promiscuity and large pollution induced by human and
      animal excreta. One district, located in the centre of the town, was surveyed for
      drinking water quality (ammoniac and bacterial count) and use, as well as for the
      prevalence of parasites through both a random sample (fixed tools with methiolate
      iodine-formaldehyde) and a systematic one (scotch-test). Water consumption was
      16.5 litres/day/man from fresh water supplies (87%) and private wells (13%).
      Ammoniac measures were low in the wells but high in running water (pool and
      river). It was the same for faecal coliform bacteria. These results give evidence
      of biotope faecal pollution. The random sample (322 persons, male/female sex
      ratio 0,85, average age 20,6 years) showed a 42.1% parasitic prevalence. Amoeba
      was the most frequent parasite (53.6%); and Giardia (14.9%) was the most frequent
      pathogenic parasite. In the second sample (161 children under 10 years), 24.2%
      were carriers of oxyuris. This large intestinal parasitism, without any change in
      connection with previous data in Niger, points to an important fecal
      contamination of the people more by the way of "dirty hands" than consumption of
      drinking water. The parasites observed have a short biological cycle, not
      necessitating long-term maturation in the environment. Those whose ova or larvae
      must complete their cycle outside have no possibility of surviving in Sahel,
      thanks to the beneficial effect of sunlight (heat and ultraviolet light). The
      inhabitants of this district seem to have adapted to intestinal parasitism. But
      the occurrence of malnutrition linked to a new drought could lead rapidly to a
      very serious adverse result.

PMID- 10078380
TI  - [Viral hepatitis of enteric origin].
AB  - Hepatitis viruses of oral-fecal origin are responsible for a high morbidity and
      mortality throughout the world, even if they never result in chronic hepatitis.
      Two viruses, the virus of hepatitis A (VHA) and of hepatitis E (VHE) are at
      present the cause of severe viral hepatitis of enteric origin. Water is the
      principle vector in the spread of these viruses. However, the epidemiological
      aspects vary according to the pathogenic agent. VHA is excreted in a highly
      concentrated form in the feces for a relatively short period of time. Since it
      resists in an exterior environment, the virus remains infectious for a long time.
      VHE is excreted for a short period of time and in low concentrations. The viral
      particles are fragile in vitro and their variability in the environment is little
      known. The possible reservoir role of certain animals has been envisaged.
      Epidemics arise especially in countries suffering from poor hygiene and massive
      water pollution. Hepatitis A should no longer be considered a benign disease of
      childhood. The progress made in hygiene and economic development in
      industrialized countries have made contacts with this virus scarce, rendering the
      populations more receptive to it and epidemics more widespread. When the sickness
      occurs later in life, infection is more often symptomatic and can be serious,
      resulting sometimes long-term indisposition. Hepatitis E has a vast distribution
      throughout the world and manifests itself either in epidemic or endemic-sporadic
      form in many poor countries. In developed countries, it comes about mostly as a
      result of imported pathology, even if there exists a "substratum" of infection in
      these areas. The main clinical aspects, such as we were able to study them in 39
      cases of military men from Tchad, Guyana and Somalia, are comparable to those of
      hepatitis A. The reasons for the particular gravity of symptoms in pregnant women
      are unknown. These affections have no specific treatment. In the field of
      prevention, vaccination is at present the best means for hepatitis A prophylaxis.
      Until a vaccine against hepatitis E is found, prevention depends on hygiene,
      sanitation measures et distribution of drinking water.

PMID- 10078381
TI  - [Rotavirus and other viruses of diarrhea].
AB  - Rotaviruses represent 80% of recognized viral etiologies and 140 million cases of
      diarrhea per year. They strike young children with similar frequency throughout
      the world, but the mortality rate is high in developing countries only, with some
      870,000 deaths per year (WHO, 1997). Rotaviruses belong to the family of
      Reoviridae; they are segmented bicatenary RNA viruses, which explains their
      genetic variability, the presence of mixed infections, the establishment for some
      time already of a molecular epidemiology by electrophore types. The viruses are
      "naked" and thus resistant to the outside environment; their massive elimination,
      10(8) to 10(10)viral particles per gram of faeces, begins with the first day of
      diarrhea. They are found in used water and can also be concentrated by shellfish;
      the environment thus constitutes a notable reservoir for the virus. Oral-faecal
      transmission is facilitated by deficient sanitary conditions. The 11 fragments of
      the genome each codify for 1 viral protein; 2 surface proteins, VP4 and VP7,
      bring about the formation of neutralizing antibodies, which are important for the
      protection and determination of different serotypes. A non structural protein-
      NSP4--would seem to intervene in the cytopathogenic effect and may act as a
      veritable viral enterotoxine. Numerous animal species are infected by rotaviruses
      which are district from the human ones. The pathology as it affects animals is of
      economic importance and of interest as an experimental and vaccinal model.
      Between human and animal rotaviruses there can be genetic rematchings and the VP6
      protein is an antigen common to the group. The description of the other viruses
      responsible for diarrhea has benefited from widespread use of electronic
      microscopes from the very first years of study of rotaviruses. These other
      viruses belong to 6 different types: adenovirus, calcivirus, astrovirus, Norwalk
      agent and related viruses, coronavirus, enterovirus. They therefore have a
      structural and antigenic polymorphism but, except for the coronavirus, they are
      all "naked" virions with resistance in outside environments and means of
      transmission analogous to the rotaviruses. Clinical signs of viral
      gastroenterites, the age of the patient and epidemiological circumstances help in
      making an etiological diagnosis; the biological diagnosis has been simplified for
      the rotaviruses and the adenoviruses. Epidemics related to food, or of hydric and
      nosocomial origin, especially those due to the Norwalk agent, are under-declared
      and more frequent than those of bacterial origin. The prevention of dangers
      related to faeces, the improvement of sanitary conditions, health education, and
      better nutrition contribute to rotavirus prevention, but rotavirus diarrheas, the
      incidence of which is similar in developed and developing countries, would be
      more efficiently controlled through vaccination.

PMID- 10078382
TI  - [Public hygiene, microbiology and water management].
AB  - Over the last hundred and fifty years, hygienists and health-related water
      microbiologists have laid down rules of public hygiene and sanitary systems to
      protect the health of populations. This program has proven to be particularly
      effective against "fecal peril". But in developed countries waterborne infectious
      disease nevertheless still persists. This fact has led to much research on
      contamination due to waterborne micro-organisms. The emergence of the paradigm of
      risk assessment should allow microbiologists to focus their research effort on
      priority areas of prevention.

PMID- 10078383
TI  - [Vaccines inf the prevention of fecal hazards].
AB  - In addition to the imperative improvement of hygiene standards, vaccines can also
      be used for the prevention of diseases transmitted by the feco-oral route.
      Vaccination is essential to protect against poliomyelitis, the eradication of
      which is targeted through vaccination campaigns using the live, attenuated
      vaccine in countries where the disease is still endemic and the inactivated
      vaccine or a combination of both vaccines (mixed schedule) in countries where the
      disease is under control. The introduction of a specific routine vaccination
      program against hepatitis A in endemic countries is now starting to be
      considered. Travellers to these countries must be protected. Among bacterial
      diseases, only typhoid fever can be prevented by means of an effective vaccine.
      The difficulties encountered in improving hygiene standards in numerous countries
      have prompted the WHO to encourage search for new vaccines for the prevention of
      the diseases transmitted by the feco-oral route. A vaccine against rotavirus that
      has just been licensed in the USA should permit the global reduction of a
      significant number of deaths attributable to these viruses. Vaccine prospects for
      the prevention of hepatitis E are more distant. Several vaccines against Shigella
      (injectable polysaccharide conjugate vaccine or oral, live, attenuated vaccines
      obtained by construction of mutant strains) and enterogenic Escherichia coli
      (oral, inactivated vaccine containing several strains of ETEC and sub-unit B of
      the cholera toxin), not to mention candidate vaccines against cholera.

PMID- 10078384
TI  - [Traveller's diarrhea: progress and lessons drawn from recent surveys].
AB  - Diarrhea among travellers continues to be as widespread as ever. A multicentric
      investigation carried out in Jamaica, Kenya, Goa (India) and Fortaleza (Brazil)
      indicates high incidence rates and enterotoxigenic Escherichia coli are the most
      common etiology for each destination.

PMID- 10078385
TI  - [Principles and management of the ambulatory treatment of traveller's diarrhea].
AB  - Traveller's Diarrhea (TD, turista) is the most common health disturbance in
      travellers, affecting 20-50% of two-week travellers depending on their origin,
      destination and eating habits. The etiological agents most frequently isolated
      from the stools are enterotoxinogenic Escherichia coli (ETEC), Salmonella spp.,
      Shigella spp., but the rate of isolation of Campylobacter spp. and non cholera
      vibrios is also high in Asia. Preventive measures in eating habits should in
      principle be able to curb the incidence of TD but compliance of travellers is
      usually poor. Antibiotic chemoprophylaxis has proved effective, but economic,
      safety and microbiological (drug resistance) considerations discourage its
      widespread use. Any treatment strategy should consider that TD is usually a self
      limiting, benign illness in most travellers, even though infants, elderly people
      or persons with severe baseline diseases (heart diseases, diabetes,
      immunocompromised hosts, etc...) may sometimes suffer severe consequences.
      Adequate rehydration is the cornerstone of treatment and intestinal motility
      inhibitors may be used in adults (not in children) with severe diarrhea during
      the first 24 hours if the suspicion of invasive pathogen has been ruled out.
      Routine antibiotic treatment of TD is controversial, due to the benign nature of
      the syndrome and to the impossibility to ascertain its causative agent. It should
      be limited to severe and disabling cases. Among the many antibiotics tested,
      quinolones are now considered first-choice treatment worldwide, even though
      disturbing reports of the increasing prevalence of quinolone-resistant
      Campylobacter spp. from Asia have been recently published. Cotrimoxazole is
      efficient in Central America. The role of non absorbed antibiotics and probiotics
      is still to be fully elucidated.

PMID- 10078386
TI  - [Traveller's diarrhea: which vaccines?].
AB  - Diarrheal diseases are a major cause of child morbidity and mortality,
      particularly in developing countries. It is estimated that diarrheal diseases and
      typhoid fever cause around 2.5 million deaths per year in the world. Four
      bacteria and one virus share this responsibility: Shigella spp, Escherichia coli
      ETEC, Vibrio cholerae, Salmonella typhi and rotavirus. People travelling in
      countries with high endemicity of diarrhoeal diseases risk facing these four
      bacteria or the less common rotavirus, which is usually active in infants, even
      though some cases of diarrhoea due to rotavirus have already been reported in
      adults. The usual recommendations concerning basic measures of hygiene are most
      of the time quickly forgotten and followed only by a small number of travellers
      (12). Therefore, apart these useful recommendations, it is therefore necessary to
      consider complementary actions for controlling these diseases which are mainly
      transmitted by contaminated water and food. This article aims at giving an
      overview of currently available and future vaccines for preventing travellers'
      diarrheas.

PMID- 10078387
TI  - [Emergency consultations of foreign tourists in Paris in the month of August. 5
      years of prospective surveillance (1992-1996)].
AB  - For five consecutive years, five major Parisian institutions in charge of
      emergencies have participated in a prospective collection of medical data for
      foreign patients visiting Paris in August; 4093 subjects have been studied.
      Gastroenteritis represented the main cause in calling on emergency medical care
      (14.5 to 21.9%), followed by traumatology, ear-nose-throat problems, syndromes
      labelled as viral, skin problems: these five categories represented 60 to 64% of
      all the serious problems encountered by tourists. The statistical frequency of
      different causes in calling on emergency care varied significantly according to
      two variables: the tourists' age and nationality. The incidence of
      gastroenteritis is estimated at between 13 and 30 per 100,000 visitors and the
      incidence of pathological problems taken all together--at 80 to 100 per 100,000.

PMID- 10078388
TI  - [Management of foreign tourists' diseases at the American Hospital in Neuilly].
AB  - More and more foreign tourists are being treated at the American Hospital of
      Paris. The main reasons for this are the presence of a 24 hour medical and dental
      emergency service, in addition to the availability of MRI, CT scan and
      comprehensive laboratory facilities. The hospital is multidisciplinary, where
      short stay hospitalizations are the rule. English is the second most commonly
      used language. There is a permanent Japanese language service for Japanese
      patients. Qualitative data is presented concerning the management of patients
      according to specialty and nationality. American and Japanese patients admitted
      to the hospital in 1997 are surveyed according to their mean age, reasons for
      admission and appropriate specialty as well as mean length of stay noted. The
      greatest number of hospitalizations in decreasing order and according to
      nationality are as follows: American, Japanese, Moroccan Egyptian and Saudi
      Arabian. The consultations and hospitalizations of Japanese patients between 1990
      and 1997 are compared.

PMID- 10078389
TI  - [The principal arthropod vectors of disease. What are the risks of travellers' to
      be bitten? To be infected?].
AB  - Many blood-sucking arthropods are potential vectors of disease. To become a
      vector, the arthropod must be susceptible to the infective agent and must survive
      the incubation period so as to transmit the pathogens to a host. While some
      arthropod associated diseases affect only man (e.g. malaria) most of these
      diseases are (anthropo-) zoonoses with man often an accidental host. The risk of
      contamination depends on the one hand on the biting behaviour of the vector, its
      biology and distribution, and on the other hand on the sites visited by the
      traveller, the length of his stay, his activities, the conditions of sleeping
      accommodation. The risk of contracting malaria is very high in tropical Africa,
      in the forest area of South America and South East Asia, in Papua New Guinea.
      Malaria can be prevented if measures (e.g. pyrethroid impregnated bed nets,
      repellents) are taken to avoid bites of Anopheline mosquitoes between sunset and
      sunrise, but appropriate chemoprophylaxis must not be neglected. Lethal cases of
      yellow fever among unvaccinated travellers still occur despite a strict
      international regulation on vaccination requirements. Dengue is a major health
      problem in intertropical areas. As no vaccine is available, personal protection
      measures are recommended against daytime-biting mosquitoes, including the use of
      protective clothing, repellents. Other arthropod borne diseases among travellers
      are less common but the risks increase during adventure trips (e.g. zoonotic
      leishmaniasis, tick-borne relapsing fever) and humanitarian actions (e.g. risk of
      louse-borne typhus during visits of overcrowded prisons). Tick-borne diseases
      receive nowadays more attention. These diseases are not only restricted to some
      occupations (farmers, veterinarians) but also ramblers and campers are at risk.
      Attached ticks should be removed rapidly and carefully, since several hours of
      attachment are needed for transmission of spirochetes of LYME disease.

PMID- 10078390
TI  - [Protection of travellers against biting arthropod vectors].
AB  - Several diseases are transmitted by hematophageous insect/arthropod and, except
      for yellow fever and Japanese B encephalitis, there are still no vaccines.
      Personal protection therefore remains the choice method for disease prevention
      and can usefully complete chemoprophylaxis if available (such as for malaria).
      Personal protection can be ensured by three main methods: avoiding risky areas;
      using repellents on skin and/or garments; using pyrethroids insecticide on
      garments (permethrin), mosquito nets (several Pyr. available) and any other
      materials (curtains etc.) including camping tents, plasting "UN sheeting" used in
      refugees camps etc. Repellent gave some protection for few hours (# 6 hours) and
      new formulations have been developed to extend their duration. Great care must be
      taken when using DEET which is not recommended for children and pregnant women.
      Coils and mats can be used but care must also be taken when using some coils
      available on local market and which can often be irritating and useless. Mosquito
      nets impregnated with an insecticide remains the choice method of protection
      against night-biting insects such as anopheles and is a good way of preventing
      malaria. Insecticide must be used according to safety measures clearly indicated
      (or which must be clearly indicated) by companies. All these measures are
      efficient and must be selected according to local conditions and human behaviour.
      Travelling is not "risky" but 3 points must be kept in mind: accurate advice must
      be sought before travelling; this advice must be followed while persuing a
      "normal life"; a physician must be consulted in case of any trouble during and
      after the trip.

PMID- 10078391
TI  - [Legionnaires' disease in travellers].
AB  - The outbreak of pneumonia involving delegates to the 1976 American Legion
      convention at a Philadelphia hotel was the first example of travel-associated
      legionnaires' disease. Travel is now well known as a common risk factor for
      legionnaires' disease. This travel-associated disease is a preoccupation among
      European countries because of morbidity among citizens of the European Union. The
      definition of the case of legionellosis is a patient who presents an acute lower
      respiratory tract infection with focal signs of pneumonia and/or radiological
      features, and microbiological evidence of Legionella infection. A case is
      considered to be travel associated if the patient has spent one or more nights
      away from home during the ten days before becoming ill. An European Surveillance
      Scheme for Travel-Associated Legionnaires' Disease was established in 1987 to
      identify clusters and outbreaks of cases of the disease. This group centralizes
      the case reports of twenty-nine collaborating centres in twenty-five countries.
      Outbreaks of legionnaires' disease were described in hotels, camps or cruise
      ships. In 1996, the number of travel-associated cases of legionnaires' disease
      represented 16% of the total number cases. The increase of the number of reported
      cases may reflect improved surveillance and increased ascertainment. In Europe in
      1996, the diagnosis of legionellosis was confirmed by detection of Legionella
      pneumophila sero-group 1 antigen in urine (36%), seroconversion (fourfold rise in
      antibody titre, 33%) and culture of the organism (16%). Fifteen per cent of
      legionellosis was diagnosed by the identification of a single high antibody
      titre. In France a coordination between Public Health Institutions (Reseau
      National de Sante Public and DDASS), clinicians, laboratories and National
      Reference Center was established to improve prevention and control of
      legionnaires' disease outbreaks. Legislation obliges to report each case. When
      more two cases in the same area are notified an epidemiological investigation
      must be done. The knowing of the source of the contamination and its eradication
      allows to prevent new cases and outbreaks. Outbreaks of Legionnaires' disease are
      even now mediatic and this fact leads to maintain attention for the quality of
      diagnosis and epidemiology investigation due to touristic and economic
      consequences for the implicated countries.

PMID- 10078392
TI  - [Resistance to chloroquine and cycloguanil of Plasmodium falciparum in patients
      arriving in France after travel in Africa without chemoprophylaxis].
AB  - The in vitro susceptibility of chloroquine and the genomic profile of
      dihydrofolate reductase (DHFR) codon 108 was determined against african isolates
      of P. falciparum (Pf) from imported malaria cases without previous drug intake by
      an isotopic microtest or PCR + RFLP. Pf resistance to chloroquine or to the DHFR
      inhibitor was present in 49% and 46% of isolates, respectively. Pf drug
      resistance was more frequent in permanent than in seasonal malarial transmission
      areas and chloroquine plus DHFR resistance reached 28% in years 1995-97. Updating
      the guidelines for the prevention of malaria in travellers to Africa is
      necessary.

PMID- 10078393
TI  - [The proper use of antimalarial drugs currently available].
AB  - French medical practitioners have at their disposal several antimalarial drugs
      for giving chemoprophylaxis to people travelling to a malaria endemic country or
      treating an imported malaria case in a patient. The choice depends on the contre
      indications and indications of each drug, essentially subordinated to the
      presence and level of Plasmodium falciparum chemosensitivity in the visited area.
      For prevention, chloroquine alone can be taken in the areas where P. falciparum
      is absent or not chloroquine resistant; elsewhere, the choice between
      chloroquine/proguanil or mefloquine depends on knowing the prevalence and level
      of falciparum chloroquine resistance in these areas. For treatment, the only
      indications of chloroquine are imported malaria cases either due to P. vivax, P.
      ovale or P. malariae, or caused by P. falciparum contracted in one of the rare
      countries where the species is still sensitive to chloroquine. For uncomplicated
      falciparum malaria cases acquired in a chemoresistance area, mefloquine,
      halofantrine, sulfadoxine-pyrimethamine or oral quinine is selected, depending on
      the observed chemoprophylaxis, the contra-indications and the suspicion of
      chemoresistance type. Whatever the provenance area, P. falciparum in a patient
      with one or several serious symptoms or possibly profuse vomiting is treated by
      intravenous quinine, associated with tetracycline if the patient comes from an
      area known for a low quinine sensitivity of this species. The spectrum of
      falciparum malaria treatment has recently broadened to include new drugs such as
      artemisinin, artemether or atovaquone/proguanil, the latter being as yet
      unauthorized in France.

PMID- 10078394
TI  - Diphthongs, drug labels and new media.

PMID- 10078395
TI  - Outcomes analysis can provide new directions for the management of patients
      undergoing lumbar spine surgery.

PMID- 10078396
TI  - Early postoperative complications following neurosurgical procedures.
AB  - PURPOSE: To assess the incidence and characteristics of early postoperative
      complications in patients following neurosurgical procedures. METHODS: All
      patients undergoing neurosurgery during a four month period were followed
      postoperatively for up to four hours in the post anesthetic care unit or
      intensive care unit. Patient information and all complications were documented by
      the investigators on a standardized form. Complications were classified as
      respiratory, cardiovascular, nausea and vomiting, shivering and other. Risk
      factors analyzed for the occurrence of complications included age, sex, ASA
      status, type of surgery, elective or emergency surgery and postoperative
      placement. RESULTS: Four hundred eighty six adult patients were followed, but in
      55 patients the trachea remained intubated during the four hour study period and
      they were eliminated from the analysis of postoperative complications. At least
      one complication occurred in 54.5% of the remaining 431 patients. Respiratory
      problems occurred in 2.8%, trauma to the airway in 4.4%, cardiovascular
      complications in 6.7%, neurological in 5.7% and nausea and/or vomiting in 38%.
      The highest incidence of patients with complications was during spine (65%) and
      vascular (66%) surgery, compared with tumour (47%) and other (43%) surgery, P <
      0.05. Other risk factors included age < 70 yr for nausea and vomiting (P < 0.02),
      and elective surgery for spine and vascular surgery (P < 0.001). CONCLUSION:
      There was a high incidence of early postoperative complications in neurosurgical
      patients. The most common problem was nausea and vomiting especially in the
      younger patient undergoing elective spine surgery.

PMID- 10078397
TI  - [Hemodynamic monitoring using esophageal Doppler ultrasonography during
      laparoscopic cholecystectomy].
AB  - PURPOSE: To evaluate the use of a 4-mHz continuous wave esophageal Doppler
      monitor in the hemodynamic management of 48 ASA I to III patients undergoing
      laparoscopic cholecystectomy. METHODS: General anesthesia was induced with
      fentanyl and propofol, maintained with N20 N20/02 and muscle relaxation was
      provided with atracurium. The lungs were mechanically ventilated. Non invasive
      arterial blood pressure, heart rate, capnography, arterial blood gas were
      monitored during CO2 pneumoperitoneum at 15-mmHg. Using the velocity waveform of
      descending aortic blood flow, the Doppler device estimated changes in cardiac
      output and systemic vascular resistances. RESULTS: Peritoneal insufflation
      resulted in a mean 19% decrease in cardiac output (range -49 to +5%; P < 0.05)
      and a mean 48% increased in systemic vascular resistances (range -7 to +101%; P <
      0.01). There was no relationship between changes in cardiac output and mean
      arterial pressure or PETCO2. The esophageal Doppler provided, in two patients,
      details of hypertensive peaks (mean arterial pressure > 140 mmHg) which responded
      to administration of nicardipine. CONCLUSION: The Esophageal Doppler provided an
      easy-to-handle and non invasive tool to monitor changes in cardiac output during
      laparoscopic cholecystectomy. However, further comparison with a thermodilution
      cardiac output technique is required.

PMID- 10078398
TI  - Sevoflurane-maintained anesthesia induced with propofol or sevoflurane in small
      children: induction and recovery characteristics.
AB  - PURPOSE: To compare the induction and recovery characteristics of sevoflurane
      anesthesia induced with either propofol or sevoflurane in pediatric outpatients.
      METHODS: Fifty-two children, aged 1-3 yr, presenting for ambulatory adenoidectomy
      were randomly allocated to receive 3 mg.kg-1 propofol i.v. or sevoflurane 8%
      inspired concentration for induction of anesthesia. Tracheal intubation was
      facilitated with 0.2 mg.kg-1 mivacurium. Anesthesia was maintained with nitrous
      oxide/oxygen (FiO2 0.3) and sevoflurane approximately 3-5% inspired concentration
      with controlled ventilation. Intubation was assessed by an anesthetist blinded to
      the induction method. Recovery characteristics were compared using the modified
      Aldrete scoring system, the Pain/Discomfort scale and measuring specific recovery
      times. A postoperative questionnaire was used to evaluate the children's well
      being at home. RESULTS: Intubating conditions were similar in both groups.
      Emergence from anesthesia occurred earlier with sevoflurane for induction than
      with propofol (11 +/- 4 vs 17 +/- 7 min (mean +/- SD), P = 0.0002). More children
      in the sevoflurane group achieved full points on the modified Aldrete scoring
      system during the first 20 min after anesthesia (P < 0.05). However, children in
      the sevoflurane group scored higher in the Pain/Discomfort scale at 10 min after
      anesthesia (P = 0.04) and were given postoperative analgesics earlier than
      children in the propofol group (13 +/- 5 min vs 18 +/- 11 min, P = 0.03). The
      time to meet discharge criteria and recovery at home were similar. CONCLUSIONS:
      Induction of sevoflurane anesthesia with propofol for day-case adenoidectomy
      results in longer, but more calm, early recovery but does not delay discharge or
      affect recovery at home.

PMID- 10078399
TI  - Potency and time course of mivacurium block during sevoflurane, isoflurane and
      intravenous anesthesia.
AB  - PURPOSE: To determine the potency and time course of action of mivacurium
      neuromuscular block under routine clinical conditions during sevoflurane,
      isoflurane and intravenous anesthesia. METHOD: Patients were anesthetized with
      nitrous oxide 66% in oxygen and 1.5 MAC sevoflurane or isoflurane or a propofol
      infusion, neuromuscular block being monitored using mechanomyography. Potency was
      determined using administration of single doses of mivacurium of 40-100
      micrograms.kg-1 and construction of dose-response curves (n = 72). The onset and
      duration of action were determined following a bolus dose of 0.2 mg.kg-1 of
      mivacurium (n = 30). RESULTS: The ED50 and ED95 (with 95% confidence limits) were
      estimated to be 42 (35-51) and 86 (74-98) micrograms.kg-1, 52 (45-60) and 89 (72
      110) micrograms.kg-1, and 53 (45-62) and 95 (81-112) micrograms.kg-1 during
      sevoflurane, isoflurane and propofol anesthesia respectively (P < 0.05 between
      sevoflurane and propofol). Following administration of the 0.2 mg.kg-1 dose,
      neither the times (mean +/- SD) to maximum block (1.6 +/- 0.31, 1.7 +/- 0.21 and
      1.6 +/- 0.45 min, respectively) nor the times to 25 and 90% recovery of T1 (20 +/
      4.5 and 33 +/- 8.8 min, 21 +/- 3.8 and 33 +/- 6.5 min, and 18 +/- 4.1 and 28 +/-
      5.8 min respectively) were different among groups. The times to recovery of TOF
      ratio to 0.8 were 40 +/- 10.0, 36 +/- 8.5 and 29 +/- 5.5 min in the sevoflurane,
      isoflurane and propofol groups respectively (P = 0.017 between the sevoflurane
      and propofol groups). CONCLUSIONS: Under usual conditions of clinical anesthesia
      the potency of mivacurium was slightly enhanced during sevoflurane compared with
      intravenous anesthesia but the duration of action was only minimally prolonged
      during sevoflurane and isoflurane anesthesia.

PMID- 10078400
TI  - Efficacy of three test doses to detect epidural catheter misplacement.
AB  - PURPOSE: To determine among three currently used epidural test doses which is the
      most reliable for the detection of accidental intrathecal misplacement of an
      epidural catheter, and which clinical sign is to be used as a marker. METHODS:
      Ninety orthopedic patients were allocated to either the continuous epidural or
      the continuous spinal group according to age, < or > 70 yr. They received, in a
      randomized, double-blind fashion, one of the three solutions: 60 mg lidocaine 2%
      (L2%), 7.5 mg bupivacaine 0.25% (B0.25%), or 15 mg bupivacaine 0.5% (B0.5%); all
      three solutions contained epinephrine. Objective variables studied every two
      minutes over the first ten minutes after injection included: presence of a
      sensory level > or = T12, presence of a motor block > or = 1, and anesthesia of
      segments L1, L2, S2 and S5. Subjective variables studied over the same period
      included paresthesias, sensation of warmth or cold, and muscle weakness. RESULTS:
      When using presence of motor block > or = 1 on the Bromage scale, the
      administration of 60 mg L2% with epinephrine identified all patients having an
      intrathecal catheter six minutes after injection, whereas none of the patients
      receiving the same solution through the epidural catheter presented a motor
      block. This was not the case for the other two solutions studied. CONCLUSION:
      Lidocaine 2% with epinephrine at a dose of 60 mg is the test dose of choice to
      detect the intrathecal misplacement of an epidural catheter. The presence of
      motor block > or = 1 is the only reliable clinical sign.

PMID- 10078401
TI  - Comparison of ondansetron with ondansetron and dexamethasone in prevention of
      PONV in diagnostic laparoscopy.
AB  - PURPOSE: To compare the efficacy of ondansetron-dexamethasone combination with
      ondansetron alone for prevention of postoperative nausea and vomiting (PONV).
      METHODS: This double blind, randomized study was carried out in 51 female
      patients, aged 20-40 yr, ASA-1 physical status undergoing gynecological
      diagnostic laparoscopy. Group 1 (n = 26) received 4 mg ondansetron i.v. and group
      2 (n = 25) received a combination of 4 mg ondansetron and 8 mg dexamethasone i.v.
      soon after induction of anesthesia. Postoperatively patients were assessed hourly
      for four hours and then at 24 hr for nausea, vomiting, pain and post anesthetic
      discharge score. Vomiting occurring up to two hours was considered early vomiting
      and from 2-24 hr as delayed vomiting. RESULTS: The postoperative nausea score was
      lower in patients receiving a combination of ondansetron and dexamethasone (3.76)
      than ondansetron alone (4.38) at 0 hr (P < 0.01), 2 hr (P < 0.05) and 24 hr (P <
      0.01). In group 1, 38.5% of patients had a nausea score of > or = 5 (major
      nausea) compared with only 12% of patients in group 2 (P < 0.025). The overall
      incidence of vomiting was greater in group 1 (35%) than in group 2 (8%) (P <
      0.05). The combination group showed better control of delayed vomiting compared
      with the ondansetron group (4% vs 35%) (P < 0.01). CONCLUSION: The combination of
      ondansetron and dexamethasone provides adequate control of PONV, with delayed
      PONV being better controlled than early PONV.

PMID- 10078402
TI  - Oral granisetron for strabismus surgery in children.
AB  - PURPOSE: To determine the efficacy of oral granisetron in preventing
      postoperative vomiting (POV) following strabismus repair in children. METHODS: In
      a randomized, double-blind, placebo-controlled trial, 73 pediatric patients
      received either placebo, 20 micrograms.kg-1 or 40 micrograms.kg-1 granisetron po
      20 min before induction of anesthesia. No premedication was given, induction was
      with halothane and all children breathed spontaneously via a laryngeal mask
      airway. Maintenance was with isoflurane without the use of opioids. Ketorolac and
      acetaminophen were used for analgesia. The number of episodes and the severity of
      vomiting and retching were recorded for the first 24 hr postoperatively, as was
      the use of rescue antiemetics. RESULTS: Granisetron 20 micrograms.kg-1 and 40
      micrograms.kg-1 were more effective than placebo in reducing the incidence of POV
      during the first 24 hr (29% in both the granisetron groups vs 84% in the placebo
      group, P < 0.05). In addition, the number of children experiencing severe
      vomiting (> or = 3 episodes) was reduced in the granisetron 20 micrograms.kg-1
      and 40 micrograms.kg-1 groups compared with placebo (4%, 8% and 48% respectively,
      P < 0.05). Patients in the granisetron group were discharged home earlier (105
      min vs 124 min, P = 0.04). There was no difference in the incidence of POV
      between the two granisetron groups. CONCLUSION: Preoperative oral granisetron in
      a dose of 20 micrograms.kg-1 provided effective prophylaxis against POV in
      children undergoing stabismus repair.

PMID- 10078403
TI  - Low dose mivacurium is less effective than succinylcholine in electroconvulsive
      therapy.
AB  - PURPOSE: To compare the efficacy of low dose (LD) mivacurium (0.08 mg.kg-1) with
      LD succinylcholine (0.5 mg.kg-1) in modifying seizure activity during
      electroconvulsive therapy (ECT). Partial muscle relaxation is used in ECT to
      prevent violent muscle contractions. Current practice is to use LD
      succinylcholine which has several undesirable side effects. METHOD: Sixteen
      depressed, but otherwise healthy, patients, aged 27-67 yr were studied. In a
      randomized, double-blind, cross-over study, either LD mivacurium or LD
      succinylcholine was given at consecutive ECTs 120 and 30 sec respectively before
      inducing ECT. Neuromuscular blockade following mivacurium was not reversed.
      Seizure modification was scored--0 = no seizure activity, 1 = over-modified, 2 =
      desired level, 3 = under-modified, 4 = unmodified. Duration of seizures, time to
      first breath and adequate ventilation, ability to protrude tongue and sustain
      hand grip for five seconds were recorded. Paired t-tests and Wilcoxon matched
      pairs test were used to compare data. P < 0.05 was considered significant.
      RESULTS: Seizure modification was better (mean (range)) after succinylcholine
      2.06(1-3) than after mivacurium 2.56(2-4) (P < 0.05). Mivacurium was
      unsatisfactory in eight cases compared with two cases after succinylcholine. The
      study was terminated early because of unsatisfactory seizure control. Clinical
      assessments of recovery from both relaxants were similar. CONCLUSION: Low dose
      mivacurium is unsuitable for use in ECT.

PMID- 10078404
TI  - ST-segment depression and myocardial contractility during cesarean section under
      spinal anesthesia.
AB  - PURPOSE: To evaluate myocardial contractility during ST segment depression in
      healthy parturients during Cesarean section (CS). METHODS: Forty-seven
      consecutive term parturients undergoing elective CS under spinal anesthesia were
      studied. The ST segment was recorded continuously on leads II and V5 using a
      Holter monitor. Myocardial performance was evaluated by measuring cardiac index
      (CI), heart rate (HR), pre-ejection period (PEP), ventricular ejection time
      (VET), systolic time ratio (STR, PEP/VET), and ejection fraction (EF) with an
      impedance cardiograph. RESULTS: Fourteen patients (30%) developed ST segment
      depression within 15 min after delivery and the remaining 33 (70%) did not
      (controls). Seven patients developed a 1 mm change, five patients a 2 mm change
      and the remaining two a 3 mm change in the ST segment. Compared with pre
      anesthesia values, the mean HR increased from 103 +/- 10 to 116 +/- 10 (ISD) bpm
      (P = 0.001), CI from 4.7 +/- 0.7 to 5.6 +/- 1.7 L.min-1 (P = 0.01), EF from 0.58
      +/- 0.08 to 0.66 +/- 0.05 (P = 0.01) and STR decreased from 0.26 +/- 0.06 to 0.2
      +/- 0.04 (P = 0.01) during ST segment depression. At this time, CI, HR and EF
      were greater and STR smaller than values obtained 15 min after delivery in the
      control subjects. CONCLUSION: ST-segment depression occurring during CS is
      associated with a hyperkinetic myocardial contractile state.

PMID- 10078405
TI  - Profound hypoxemia during treatment of low cardiac output after cardiopulmonary
      bypass.
AB  - PURPOSE: To illustrate the multiple causes of hypoxemia to be considered
      following cardiopulmonary bypass and how therapy given to improve oxygen delivery
      may have contributed to a decrease in arterial oxygen saturation to life
      threatening levels. CLINICAL FEATURES: A 61 yr old man with severe mitral
      regurgitation and chronic obstructive lung disease underwent surgery for mitral
      valve repair. A pulmonary artery catheter with the capacity to measure cardiac
      output and mixed venous oxygen saturation (SvO2) continuously was used. Two
      unsuccessful attempts were made to repair the valve which was finally replaced,
      requiring cardiopulmonary bypass of 317 min. Dobutamine 5 micrograms.kg-1.min-1
      and sodium nitroprusside 1 microgram.kg-1.min-1 were used to increase cardiac
      output. Soon after, the SvO2 decreased progressively from 55 to 39%. The patient
      became cyanotic with a PaO2 of 39 mmHg. Sodium nitroprusside was stopped and
      amrinone 100 mg bolus followed by 10 micrograms.kg-1.min-1 was given in addition
      to adding PEEP to the ventilation. With these measures PaO2 could be maintained
      of safe levels but PEEP and high inspired oxygen concentrations were needed
      postoperatively until the trachea could be extubated on the third postoperative
      day. CONCLUSION: The profound hypoxemia in this case was likely due to a
      combination of intra- and extrapulmonary shunt, both augmented by sodium
      nitroprusside. The desaturation of mixed venous blood amplified the effect of
      these shunts in decreasing arterial oxygen saturation. The interaction of these
      factors are analyzed in this report.

PMID- 10078406
TI  - Anesthesia for cesarean section in two patients with brain tumours.
AB  - PURPOSE: To describe two patients with brain tumours where general anesthesia was
      used for cesarean sections under emergency and urgent conditions. CLINICAL
      FEATURES (CASE #1): The first patient presented at 38 wk gestation with an acute
      intracranial tumour herniation, requiring emergency craniotomy and simultaneous
      cesarean section. General anesthesia was induced with thiopental and vecuronium,
      maintained with enflurane 1% in O2 100%. Maternal P(ET)CO2 was maintained at 25
      mmHg. After delivering a healthy infant, she was given syntocinon, mannitol and
      dexamethasone i.v. anesthesia was maintained with fentanyl, nitrous oxide 50% in
      O2 and isoflurane 1% during frontal-lobe tumour resection. CLINICAL FEATURES
      (CASE #2): The second patient presented at 37 wk gestation for urgent cesarean
      section because of placental insufficiency. She had had a brain tumour resection
      four years earlier. An increase in intracranial pressure necessitated craniotomy
      for decompression at 20 wk gestation. She was further treated with dexamethasone,
      carbamazepine and radiation for control of cerebral oedema at 34 wk. Cesarean
      section was performed under general anesthesia; rapid-sequence-induction with
      thiopental and succinylcholine, followed by isoflurane 1% in O2 100%. Syntocinon,
      fentanyl and atracurium i.v. were administered after delivery of a healthy
      infant. Although neurosurgeons stood by, their intervention was unnecessary.
      CONCLUSION: General anesthesia remains safe and dependable for operative delivery
      in parturients with intracranial tumour. Tracheal intubation allows maternal
      hyperventilation thereby controlling raised intracranial pressure. Hemodynamic
      stability is readily achieved to maintain cerebral perfusion. However, a
      multidisciplinary-team approach is critical for successful patient management.

PMID- 10078407
TI  - Addition of opioids alters the density and spread of intrathecal local
      anesthetics? An in vitro study.
AB  - PURPOSE: To determine whether the addition of opioids alters the density and
      spread of intrathecal local anesthetics in vitro. METHODS: In Part I, the
      densities of hyperbaric bupivacaine 0.75% (HB), hyperbaric lidocaine 5% (HL) and
      isobaric bupivacaine 0.5% (IB) with and without morphine (M), and fentanyl (F)
      were measured at 22 degrees C. In Part II a model was constructed utilizing a
      column containing a solution similar in composition to cerebrospinal fluid (CSF)
      at 37 degrees C. The various local anesthetic-opioid solutions, coloured with
      crystalline methylene blue dye, were injected at 22 degrees C into the column at
      a controlled rate through a spinal needle. The direction and extent of spread of
      the injectates were compared. RESULTS: The relative densities of the five
      solutions were: HB = HL > IB > M > F. The addition of fentanyl to IB reduced the
      density of the final solution (P < 0.05). In the model, IB alone and IB with
      morphine showed mainly downward spread, with the addition of fentanyl to IB
      resulting in upward movement (P = 0.004). The hyperbaric local anesthetics moved
      downward with or without opioids. CONCLUSION: The addition of fentanyl reduces
      the density of IB in vitro and alters its movement in simulated CSF. This may
      prove to be important in predicting the level of spinal block in clinical
      practice.

PMID- 10078408
TI  - Anesthetic modulation of myocardial ischemia and reperfusion injury in pigs:
      comparison between halothane and sevoflurane.
AB  - PURPOSE: Halothane offers protection against the reperfusion injury of the
      myocardium. This study compared sevoflurane with halothane in its potential to
      modulate the effects of acute severe ischemia and reperfusion on the myocardium.
      METHODS: Experiments were conducted on 25 pigs. Anesthesia consisted of
      thiopental, vecuronium and fentanyl. The lungs were mechanically ventilated with
      oxygen and nitrogen. Animals were randomly allocated to receive either I MAC
      halothane or sevoflurane. A control group received fentanyl and pentobarbital.
      Regional myocardial function was measured with sonomicrometers. The left anterior
      descending coronary artery was occluded for 15 min followed by 60 min
      reperfusion. RESULTS: Neither halothane nor sevoflurane protected the heart
      against the effects of acute and severe regional myocardial ischemia. During
      reperfusion, 89% of the animals receiving sevoflurane suffered from ventricular
      fibrillation compared with 30% in the halothane group (P < 0.005). Five minutes
      into the reperfusion period the animals subjected to halothane anesthesia
      demonstrated an 88% recovery in regional myocardial systolic function while in
      the sevoflurane group the recovery was 40% of pre-ischemic control (P < 0.05).
      CONCLUSION: Halothane is associated with less reperfusion arrhythmias and, in
      addition, recovery of regional myocardial function during reperfusion was more
      rapid in the presence of halothane than with sevoflurane.

PMID- 10078409
TI  - In vitro diffusion of lidocaine across endotracheal tube cuffs.
AB  - PURPOSE: Lidocaine diffuses across endotracheal tube cuffs, which may serve as a
      reservoir for local anesthetic to assist in the prevention of ETT-induced cough
      while emerging from general anesthesia. However, the rate of diffusion is slow.
      Two techniques, alkalization and warming, may increase the proportion of
      uncharged drug available for diffusion. The purpose of this study is to determine
      the effectiveness of warming alkalization or warming with alkalization on
      diffusion. METHODS: Four preparations of lidocaine 4% were studied. Group (Gr) L
      lidocaine (24 degrees C), Gr WL--warmed lidocaine (38 degrees C), Gr AL-
      alkalized lidocaine (24 degrees C), Gr WAL--warmed, alkalized lidocaine (38
      degrees C). Twenty-four Mallinckrodt 8.0 ID (Mallinckrodt Critical Care Division
      of Mallinckrodt, Inc., Glens Falls, New York) endotracheal tube cuffs were filled
      with 6 ml of one of the four preparations. They were then placed in a 20 ml water
      bath at 38 degrees C and samples were drawn from the water bath at intervals for
      up to 360 min. The lidocaine concentration in each sample was determined by gas
      chromatography. RESULTS: The highest lidocaine concentration was reached in Gr
      WAL (410.98 +/- 8.53 micrograms.ml-1) after 300 min and then decreased to 376.18
      +/- 4.59 micrograms.ml-1 after 360 min. In Gr AL the highest concentration
      (235.05 +/- 2.99 micrograms.ml-1) was reached after 360 min. Lidocaine
      concentrations in Gr L and WL after 360 min were 3.19 +/- 1.16 micrograms.ml-1
      and 4.32 +/- 2.02 micrograms.ml-1 respectively. CONCLUSION: Alkalization with or
      without warming, but not warming alone, promotes lidocaine diffusion from
      endotracheal tube cuff.

PMID- 10078410
TI  - Wire-guided endobronchial blockade in a patient with a limited mouth opening.
AB  - PURPOSE: We report the use of wire-guided endobronchial blockade, a new method of
      achieving one-lung ventilation, in a patient requiring awake, nasal, fibreoptic
      intubation for resection of a lung carcinoma. CLINICAL REPORT: A 43-yr-old woman
      with limited mouth opening, from severe TMJ dysfunction, required a right
      thoracotomy for right upper lobe wedge resection. One-lung ventilation was
      accomplished using a new type of wire-guided endobronchial blocker. The device
      was placed coaxially through the endotracheal tube using a pediatric bronchoscope
      through a special bronchoscopy port. CONCLUSION: Effective one-lung ventilation
      was achieved using this system. The system may prove advantageous in clinical
      situations where placement of double lumen endotracheal tubes or Univent tubes is
      technically impractical or impossible.

PMID- 10078411
TI  - Awareness during anesthesia.

PMID- 10078412
TI  - Concept of endotracheal intubation.

PMID- 10078413
TI  - No time to change.

PMID- 10078414
TI  - The proportion of high risk preterm infants with postoperative apnea and
      bradycardia is the same after general and spinal anesthesia.

PMID- 10078415
TI  - Halothane for supplementation of general anesthesia during cesarean section.

PMID- 10078416
TI  - Challenges and opportunities in expanded school mental health.

PMID- 10078417
TI  - Mental health in schools and system restructuring.
AB  - Because health is not the primary business of schools, a school's response to
      mental health and psychosocial concerns usually is limited to targeted problems
      seen as direct barriers to learning. And because resources are sparse, priority
      is given to problems defined in legislative mandates. As a result, school-based
      mental health services are available only to a small proportion of the many
      students who require assistance, and interventions generally are narrowly focused
      and short-term. To better meet the needs of those served and to serve greater
      numbers, emerging trends are pushing for restructuring of school-owned services
      and greater linkage with community resources to develop multifaceted,
      comprehensive, integrated approaches. This review (a) provides an overview of
      what schools currently do related to mental health and psychosocial concerns, (b)
      clarifies key emerging trends, and (c) explores implications for major systemic
      changes.

PMID- 10078418
TI  - Mental health services in schools: utilization, effectiveness, and consent.
AB  - The integration of education and behavioral health services in schools continues
      to evolve at a rapid pace. Proponents argue that school-based behavioral health
      programs have many benefits, including greater access to care and improved
      effectiveness as compared to clinic- or hospital-based services. While
      preliminary research is encouraging, in general the claims of school behavioral
      health are not supported by data. Some critics focus on negative aspects of
      school behavioral health. They claim that behavioral health is being forced upon
      students and can cite many examples of counseling and treatment administered to
      children without parental consent. Utilization, effectiveness, and consent are
      three topics that deserve a great deal of attention in this emerging field, and
      are the focus of this review.

PMID- 10078419
TI  - Integrating health and mental health services in schools: psychologists
      collaborating with primary care providers.
AB  - This article reviews recent trends, developments and empirical support for the
      expansion of psychological practice to include school-based treatment and
      management of serious and chronic medical conditions, including somatization, in
      collaboration with primary health care providers. Trends and developments
      reviewed include (a) the expansion and integration of health, mental health,
      social and community services in schools, (b) the rapid growth of school-based
      health centers (SBHCs), (c) psychology's increased involvement in the
      collaborative treatment of chronic and serious medical disorders, (d) recent
      federal and state legislative initiatives, and (e) cost-driven marketplace
      changes. Lack of empirical data specific to collaborative psychologist-health
      care provider collaboration in schools and SBHCs, particularly around
      somatization, is discussed. Ethical and legal, professional, and reimbursement
      issues that must be addressed if psychologists are to practice in this emergent
      arena are identified. This article calls for research to document both the
      clinical effectiveness and cost-efficacy of collaborative psychologist-primary
      care provider intervention in schools and SBHCs.

PMID- 10078420
TI  - Responding to the mental health needs of Latino children and families through
      school-based services.
AB  - This article highlights the value and utility of school-based mental health
      services in addressing the unmet mental health needs of Latino children and
      families in the United States. To better understand our nation's rapidly growing
      Latino population, such critical factors as demographic characteristics, cultural
      values, and family structure are examined. Special attention is devoted to the
      daunting challenges and resultant trauma experienced by many of these children
      and families who have recently immigrated to this country from war-torn home
      lands in Central America. The mental health status of Latino children is
      addressed, along with various service delivery issues and psychotherapeutic
      modalities to facilitate their personal adjustment and social adaptation in a
      culturally sensitive manner. The article concludes with the presentation of an
      innovative school-based mental health program that offers a range of services of
      demonstrated effectiveness in aiding Latino children and their families. Specific
      strategies for replicating the program model in other culturally diverse settings
      are also discussed.

PMID- 10078421
TI  - Collision or collaboration? School-based health services meet managed care.
AB  - Describes interactions of for-profit managed-care organizations (MCOs) with not
      for-profit school mental health programs that are affiliated with school-based
      health centers (SB-HCs). Discussion focuses on the developments and challenges
      that emerged between SBHCs and MCOs. While relations between MCOs and more
      traditional forms of mental health services (e.g., community mental health
      centers) are becoming established, such relations with SBHCs remain far from
      established. The example of the pathway Connecticut has taken in the continuing
      dialogue between SBHCs and MCOs is described in detail. Attention is given to the
      advocacy groups for child and adolescent mental health that were instrumental in
      convincing legislatures to enact safeguards to maintain SBHCs as providers of
      health and mental health care in the era of managed care. Challenges and
      recommendations are outlined to insure that the mental health needs of
      underserved, disadvantaged children are met through the provision of school-based
      mental health services.

PMID- 10078422
TI  - Toward collaboration in the growing education-mental health interface.
AB  - Expanded school mental health (ESMH) programs involve the provision of
      comprehensive mental health services for youth in schools, including assessment,
      intervention, prevention, and consultation. Related to increased awareness of the
      benefits of these programs, and growing disenchantment with traditional forms of
      mental health service delivery for children, ESMH programs are growing rapidly in
      the United States. Coinciding with the growth of these programs is a developing
      interface between and among education and mental health professionals in schools.
      In this interface, there is an increasing need for real collaboration; however,
      associated with differences in professional training, language, and expectations,
      and related to "turf," such collaboration is often an elusive prospect. In this
      article, we review historical trends that provide background to the growing
      education-mental health interface in schools. We discuss tensions that arise
      between staff of various disciplines when ESMH programs are developed, and
      provide recommendations on strategies to develop truly collaborative approaches
      to the provision of comprehensive mental health services in schools.

PMID- 10078423
TI  - [Gastroesophageal reflux in adults: will a consensus be possible?].

PMID- 10078424
TI  - [Gastroesophageal reflux in the adult. Definition, epidemiology, natural
      history].

PMID- 10078425
TI  - [Physiopathology of gastroesophageal reflux].

PMID- 10078426
TI  - [Diagnostic value of symptoms in gastroesophageal reflux].

PMID- 10078427
TI  - [Interpretation and role of endoscopy in gastroesophageal reflux].

PMID- 10078428
TI  - [Modalities and diagnostic criteria in esophageal ph monitoring].

PMID- 10078429
TI  - [Value of tests other than endoscopy and esophageal ph monitoring in the
      diagnosis of gastroesophageal reflux].

PMID- 10078430
TI  - [Diagnostic strategy in gastroesophageal reflux and therapeutic test].

PMID- 10078431
TI  - [Evaluation of symptoms of gastroesophageal reflux and their impact on quality of
      life].

PMID- 10078432
TI  - [Complications of gastroesophageal reflux and Barrett's esophagus].

PMID- 10078433
TI  - [Can the spontaneous course of gastroesophageal reflux be predicted and the
      therapeutic response?].

PMID- 10078434
TI  - [What are the therapeutic objectives in gastroesophageal reflux?].

PMID- 10078435
TI  - [Treatment of gastroesophageal reflux: life style-dietetic rules and topical
      agents].

PMID- 10078436
TI  - [Medical treatment of gastroesophageal reflux by H2 receptor antagonists].

PMID- 10078437
TI  - [Medical treatment of gastroesophageal reflux by prokinetic drugs].

PMID- 10078438
TI  - [Medical treatment of gastroesophageal reflux with proton pump inhibitors].

PMID- 10078439
TI  - [Consequences of achlorhydria secondary to antisecretory treatments].

PMID- 10078440
TI  - [Treatment of gastroesophageal reflux: should Helicobacter pylori infection be
      taken into account?].

PMID- 10078441
TI  - [Surgical treatment of gastroesophageal reflux: preoperative evaluation].

PMID- 10078442
TI  - [Surgical treatment of gastroesophageal reflux: modalities and results of
      classical surgery].

PMID- 10078443
TI  - [Surgical treatment of gastroesophageal reflux: modalities and results of
      endoscopic surgery].

PMID- 10078444
TI  - [Indications and contra-indications of surgical treatment of gastroesophageal
      reflux].

PMID- 10078445
TI  - [Gastroesophageal reflux in the adult: medical-economic aspects of therapeutic
      strategies].

PMID- 10078446
TI  - [Role and limits of self-medication in the therapeutic strategy of
      gastroesophageal reflux in adults].

PMID- 10078447
TI  - [Gastroesophageal reflux in the adult: initial therapeutic strategy].

PMID- 10078448
TI  - [Gastroesophageal reflux in the adult: long-term strategy].

PMID- 10078449
TI  - [Treatment of complicated forms of gastroesophageal reflux].

PMID- 10078450
TI  - [How to diagnose gastroesophageal reflux? Part 1. Diagnostic value of symptoms.
      Interpretation and role of endoscopy].

PMID- 10078451
TI  - [How to diagnose gastroesophageal reflux? Part 2: Functional examinations.
      Diagnostic strategy and therapeutic test].

PMID- 10078452
TI  - [Evaluation of gastroesophageal reflux symptoms and their impact on the quality
      of life].

PMID- 10078453
TI  - [Complications of gastroesophageal reflux].

PMID- 10078454
TI  - [Evaluation of the severity of gastroesophageal reflux: can the spontaneous
      course and therapeutic response be predicted?].

PMID- 10078455
TI  - [Gastroesophageal reflux in adults: what are the results of medical treatments?
      (I)].

PMID- 10078456
TI  - [Gastroesophageal reflux in the adult: what are the results of medical
      treatments? (II)].

PMID- 10078457
TI  - [Surgical treatment of gastroesophageal reflux].

PMID- 10078458
TI  - [Medical-economic aspects of treatment of gastroesophageal reflux].

PMID- 10078459
TI  - [Self-medication in gastroesophageal reflux: role and limits].

PMID- 10078460
TI  - [Gastroesophageal reflux: initial therapeutic strategy].

PMID- 10078461
TI  - [Gastroesophageal reflux: long-term therapeutic strategy].

PMID- 10078462
TI  - [Treatment of complicated forms of gastroesophageal reflux].

PMID- 10078463
TI  - A piece of my mind. Sherry and Richard.

PMID- 10078464
TI  - New horizons in the treatment of osteoarthritis of the knee.

PMID- 10078465
TI  - Preventive therapy for tuberculosis in HIV infection.

PMID- 10078466
TI  - HIV researchers air new findings.

PMID- 10078467
TI  - Brew it or chew it? Military seeks ways to caffeinate.

PMID- 10078468
TI  - Millennial influenza vaccine.

PMID- 10078469
TI  - FDA may get welcome new funds in its budget.

PMID- 10078470
TI  - From the Centers for Disease Control and Prevention. Needs assessment following
      hurricane Georges--Dominican Republic, 1998.

PMID- 10078471
TI  - From the Centers for Disease Control and Prevention. Human rabies--Virginia,
      1998.

PMID- 10078472
TI  - From the Centers for Disease Control and Prevention. Change in recommendation for
      meningococcal vaccine for travelers.

PMID- 10078473
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078474
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078475
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078476
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078477
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078478
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078479
TI  - Clinical crossroads: a 45-year-old man with low back pain.

PMID- 10078480
TI  - Effects of methylmercury exposure on neurodevelopment.

PMID- 10078481
TI  - Effects of methylmercury exposure on neurodevelopment.

PMID- 10078482
TI  - Oncologists' practice of euthanasia and physician-assisted suicide.

PMID- 10078483
TI  - Oncologists' practice of euthanasia and physician-assisted suicide.

PMID- 10078484
TI  - Oncologists' practice of euthanasia and physician-assisted suicide.

PMID- 10078485
TI  - Curbside consultation and malpractice policies.

PMID- 10078486
TI  - Influenza-associated morbidity and mortality in young and middle-aged women.
AB  - CONTEXT: Data are limited on rates of influenza-associated hospitalizations and
      deaths among adults younger than 65 years. OBJECTIVE: To quantify serious
      morbidity and mortality from influenza for women younger than 65 years with and
      without certain chronic medical conditions, including human immunodeficiency
      virus infection. DESIGN: Retrospective cohort study. SETTING AND POPULATION:
      Women aged 15 to 64 years enrolled in the Tennessee Medicaid program from 1974 to
      1993. MAIN OUTCOME MEASURE: All hospitalizations for and deaths from pneumonia,
      influenza, and other selected acute cardiopulmonary conditions for women with and
      without selected chronic medical conditions during 19 consecutive years.
      Influenza-attributable risk was calculated by subtracting event rates during peri
      influenza season (November through April of each year when influenza virus was
      not circulating) from adjusted rates during influenza season (November through
      April when influenza virus was circulating). RESULTS: During the 19 years of the
      study, we identified 53607 acute cardiopulmonary hospitalizations and deaths.
      Rates of such events were consistently higher during influenza seasons than peri
      influenza seasons. Among high-risk women, the estimated annual excess was 23
      hospitalizations and deaths per 10000 women aged 15 to 44 years and 58 such
      events per 10000 women aged 45 to 64 years. The estimated annual excess mortality
      due to influenza was 2 deaths per 10000 high-risk women for both age groups
      combined. Among women with no identified high-risk conditions, estimated annual
      excess hospitalizations and deaths were 4 and 6 per 10000 women aged 15 to 44 and
      45 to 64 years, respectively. CONCLUSIONS: Women younger than 65 years with
      certain chronic medical conditions experience substantial morbidity and mortality
      from acute cardiopulmonary events during influenza season. More effective
      targeting of these populations for annual influenza immunization is warranted.

PMID- 10078487
TI  - Effectiveness of influenza vaccine in health care professionals: a randomized
      trial.
AB  - CONTEXT: Data are limited and conflicting regarding the effectiveness of
      influenza vaccine in health care professionals. OBJECTIVE: To determine the
      effectiveness of trivalent influenza vaccine in reducing infection, illness, and
      absence from work in young, healthy health care professionals. DESIGN:
      Randomized, prospective, double-blind, controlled trial over 3 consecutive years,
      from 1992-1993 to 1994-1995. SETTING: Two large teaching hospitals in Baltimore,
      Md. PARTICIPANTS: Two hundred sixty-four hospital-based health care professionals
      without chronic medical problems were recruited; 49 participated for 2 seasons;
      24 participated for 3 seasons. The mean age was 28.4 years, 75% were resident
      physicians, and 57% were women. INTERVENTION: Participants were randomly assigned
      to receive either an influenza vaccine or a control (meningococcal vaccine,
      pneumococcal vaccine, or placebo). Serum samples for antibody assays were
      collected at the time of vaccination, 1 month after vaccination, and at the end
      of the influenza season. Active weekly surveillance for illness was conducted
      during each influenza epidemic period. MAIN OUTCOME MEASURES: Serologically
      defined influenza infection (4-fold increase in hemagglutination-inhibiting
      antibodies), days of febrile respiratory illness, and days absent from work.
      RESULTS: We conducted 359 person-winters of serologic surveillance (99.4% follow
      up) and 4746 person-weeks of illness surveillance (100% follow-up). Twenty
      four(13.4%) of 179 control subjects and 3 (1.7%) of 180 influenza vaccine
      recipients had serologic evidence of influenza type A or B infection during the
      study period. Vaccine efficacy against serologically defined infection was 88%
      for influenza A (95% confidence interval [CI], 47%-97%; P=.001) and 89% for
      influenza B (95% CI, 14%-99%; P=.03). Among influenza vaccinees, cumulative days
      of reported febrile respiratory illness were 28.7 per 100 subjects compared with
      40.6 per 100 subjects in controls (P=.57) and days of absence were 9.9 per 100
      subjects vs 21.1 per 100 subjects in controls (P=.41). CONCLUSIONS: Influenza
      vaccine is effective in preventing infection by influenza A and B in health care
      professionals and may reduce reported days of work absence and febrile
      respiratory illness. These data support a policy of annual influenza vaccination
      of health care professionals.

PMID- 10078488
TI  - Association of dietary intake of fat and fatty acids with risk of breast cancer.
AB  - CONTEXT: High intakes of fat and specific fatty acids, including total, animal,
      saturated, polyunsaturated, and trans-unsaturated fats, have been postulated to
      increase breast cancer risk. OBJECTIVE: To determine whether intakes of fat and
      fatty acids are associated with breast cancer. DESIGN AND SETTING: Cohort study
      (Nurses' Health Study) conducted in the United States beginning in 1976.
      PARTICIPANTS: A total of 88795 women free of cancer in 1980 and followed up for
      14 years. MAIN OUTCOME MEASURE: Relative risk (RR) of invasive breast cancer for
      an incremental increase of fat intake, ascertained by food frequency
      questionnaire in 1980, 1984, 1986, and 1990. RESULTS: A total of 2956 women were
      diagnosed as having breast cancer. Compared with women obtaining 30.1% to 35% of
      energy from fat, women consuming 20% or less had a multivariate RR of breast
      cancer of 1.15 (95% confidence interval [CI], 0.73-1.80). In multivariate models,
      the RR (95% CI) for a 5%-of-energy increase was 0.97 (0.94-1.00) for total fat,
      0.98 (0.96-1.01) for animal fat, 0.97 (0.93-1.02) for vegetable fat, 0.94 (0.88
      1.01) for saturated fat, 0.91 (0.79-1.04) for polyunsaturated fat, and 0.94 (0.88
      1.00) for monounsaturated fat. For a 1% increase in energy from trans-unsaturated
      fat, the values were 0.92 (0.86-0.98), and for a 0.1% increase in energy from
      omega-3 fat from fish, the values were 1.09 (1.03-1.16). In a model including
      fat, protein, and energy, the RR for a 5% increase in total fat, which can be
      interpreted as the risk of substituting this amount of fat for an equal amount of
      energy from carbohydrate, was 0.96 (95% CI, 0.93-0.99). In similar models, no
      significant association of risk was evident with any major types of fat.
      CONCLUSION: We found no evidence that lower intake of total fat or specific major
      types of fat was associated with a decreased risk of breast cancer.

PMID- 10078489
TI  - Plaque rupture and sudden death related to exertion in men with coronary artery
      disease.
AB  - CONTEXT: Exertion has been reported to acutely increase the risk of sudden
      coronary death, but the underlying mechanisms are unclear. OBJECTIVE: To
      determine the frequency of plaque rupture in sudden deaths related to exertion
      compared with sudden deaths not related to exertion. DESIGN: Autopsy survey.
      Coronary arteries were perfusion fixed and segments with more than 50% luminal
      narrowing were examined histologically. Ruptured plaques were defined as
      intraplaque hemorrhage with disruption of the fibrous cap and luminal thrombus.
      Exertion before death was determined by the investigator of the death. SETTING:
      Medical examiner's office. PATIENTS: A total of 141 men with severe coronary
      artery disease who died suddenly, including 116 whose deaths occurred at rest
      (mean [SD] age, 51 [11] years) and 25 who died during strenuous activity or
      emotional stress (age, 49 [9] years). MAIN OUTCOME MEASURES: The frequency and
      morphology of plaque rupture was compared in men dying at rest vs those dying
      during exertion. Independent association of risk factors (total cholesterol, high
      density lipoprotein cholesterol, glycosylated hemoglobin, cigarette smoking) in
      addition to acute exertion with plaque rupture were determined. RESULTS: The mean
      (SD) number of vulnerable plaques in the coronary arteries of men in the
      exertional-death group was 1.6 (1.5) and in the at-rest group was 0.9 (1.2)
      (P=.03). The culprit plaque in men dying during exertion was plaque rupture in 17
      (68%) of 25 vs 27 (23%) of 116 men dying at rest (P<.001). Hemorrhage into the
      plaque occurred in 18 (72%) of 25 men in the exertional-death group and 47 (41%)
      of 116 men in the rest group (P=.007). Histological evidence of acute myocardial
      infarction was present in 0 of 25 in the exertion group and in 15 (13%) of 116 in
      the rest group. Men dying during exertion had a significantly higher mean (SD)
      total cholesterol-high-density lipoprotein cholesterol ratio (8.2 [3.0]) than
      those dying at rest (6.2 [ 2.7]; P=.002), and the majority (21/25) were not
      conditioned. In multivariate analysis, both exertion (P=.002) and total
      cholesterol-high-density lipoprotein cholesterol ratio (P=.002) were associated
      with acute plaque rupture, independent of age and other cardiac risk factors.
      CONCLUSION: In men with severe coronary artery disease, sudden death related to
      exertion was associated with acute plaque rupture.

PMID- 10078490
TI  - A cluster of transfusion-associated babesiosis cases traced to a single
      asymptomatic donor.
AB  - CONTEXT: The risk of acquiring babesiosis by blood transfusion is largely unknown
      since in areas where it is endemic it is often an asymptomatic infection.
      OBJECTIVE: To investigate and treat a cluster of blood transfusion-associated
      babesiosis cases. DESIGN: Case series and epidemiologic investigation. SETTING:
      Urban inner-city hospital. PATIENTS: Six persons who received Babesia microti
      infected blood components from a donor. MAIN OUTCOME MEASURE: Diagnosis and
      successful therapy of babesiosis following transfusion. RESULTS: Six individuals
      (1 adult, 1 child, and 4 neonates) were exposed to products from a single blood
      donation by an asymptomatic Babesia-infected donor. Three of the 6 exposed
      patients became parasitemic. Polymerase chain reaction testing, animal
      inoculation studies, and indirect immunofluorescent antibody testing were used to
      confirm the presence of Babesia microti in the donor's blood and to establish the
      presence of infection in 3 of the 6 recipients. The 3 infected recipients and 1
      additional recipient were treated without incident. CONCLUSION: Physicians should
      consider babesiosis in the differential diagnosis of a febrile hemolytic disorder
      after blood transfusion. Prompt diagnosis is important since babesiosis is
      responsive to antibiotic therapy and, untreated, can be a fatal disease in
      certain risk groups.

PMID- 10078491
TI  - Postexposure chemoprophylaxis for occupational exposures to the human
      immunodeficiency virus.

PMID- 10078492
TI  - Medical futility in end-of-life care: report of the Council on Ethical and
      Judicial Affairs.
AB  - Use of life-sustaining or invasive interventions in patients in a persistent
      vegetative state or who are terminally ill may only prolong the dying process.
      What constitutes futile intervention remains a point of controversy in the
      medical literature and in clinical practice. In clinical practice, controversy
      arises when the patient or proxy and the physician have discrepant values or
      goals of care. Since definitions of futile care are value laden, universal
      consensus on futile care is unlikely to be achieved. Rather, the American Medical
      Association Council on Ethical and Judicial Affairs recommends a process-based
      approach to futility determinations. The process includes at least 4 steps aimed
      at deliberation and resolution including all involved parties, 2 steps aimed at
      securing alternatives in the case of irreconcilable differences, and a final step
      aimed at closure when all alternatives have been exhausted. The approach is
      placed in the context of the circumstances in which futility claims are made, the
      difficulties of defining medical futility, and a discussion of how best to
      implement a policy on futility.

PMID- 10078493
TI  - Global health at the crossroads: Surgeon General's report on the 50th World
      Health Assembly.

PMID- 10078494
TI  - Influenza control--unfinished business.

PMID- 10078495
TI  - Sam Ho, MD: idealist, innovator, entrepreneur. Interview by Fitzhugh Mullan.

PMID- 10078496
TI  - JAMA patient page: flu.

PMID- 10078497
TI  - Maternal smoking during pregnancy and adult male criminal outcomes.
AB  - BACKGROUND: Perinatal risk factors are related to persistent and violent criminal
      outcomes. Prenatal maternal smoking may represent an additional perinatal risk
      factor for adult criminal outcomes. Our study examines maternal smoking during
      pregnancy as a predictor of offspring crime in the context of a prospective,
      longitudinal design. METHODS: Subjects were a birth cohort of 4169 males born
      between September 1959 and December 1961 in Copenhagen, Denmark. During the third
      trimester of pregnancy, mothers self-reported the number of cigarettes smoked
      daily. When the male offspring were 34 years of age, their arrest histories were
      checked in the Danish National Criminal Register. Additional data were collected
      concerning maternal rejection, socioeconomic status, maternal age, pregnancy and
      delivery complications, use of drugs during pregnancy, paternal criminal history,
      and parental psychiatric hospitalization. RESULTS: Results indicate a dose
      response relationship between amount of maternal prenatal smoking and arrests for
      nonviolent and violent crimes. Maternal prenatal smoking was particularly related
      to persistent criminal behavior rather than to arrests confined to adolescence.
      These relationships remained significant after potential demographic, parental,
      and perinatal risk confounds were controlled for. CONCLUSIONS: Maternal prenatal
      smoking predicts persistent criminal outcome in male offspring. This relationship
      has not been accounted for by related parental characteristics or perinatal
      problems. Potential physiologic or central nervous system mediators between
      maternal smoking during pregnancy and offspring criminal outcomes need further
      study.

PMID- 10078498
TI  - Prenatal smoking and antisocial behavior.

PMID- 10078499
TI  - The influence of genetic factors and life stress on depression among adolescent
      girls.
AB  - BACKGROUND: The possible causes of greater depression among adolescent girls were
      investigated by examining variation in the influence of genetic and environmental
      risk factors among 182 prepubertal female, 237 prepubertal male, 314 pubertal
      female, and 171 pubertal male twin pairs from the Virginia Twin Study of
      Adolescent Behavioral Development. OBJECTIVES: To compare the trajectory of
      depressive symptoms among boys and girls from childhood to adolescence; to
      analyze the role of genetic, shared, and unique environmental factors in
      depression among prepubertal and pubertal male and female twins; and to
      investigate a possible link between liability to depression and one salient index
      of the child's environment: past-year life events. METHODS: Child-reported
      depression was assessed using the Child and Adolescent Psychiatric Interview and
      ratings of past-year life events and pubertal status obtained by maternal
      questionnaire and interview, respectively. RESULTS: The impact of life events on
      depression was particularly evident in the adolescent girls. The results from
      model fitting indicate increased heritability for depression in this group, and
      its long-term consistency was mediated primarily by latent genetic factors. Model
      fitting also showed that at least part of the liability to depression and to life
      events can be linked to a common set of genes in the adolescent girls, and there
      is a notable developmental increase in the genetic variance for life events.
      CONCLUSIONS: The greater heritability for depression in pubertal girls, its
      genetic mediation over time, and the increase in genetic variance for life events
      may be one possible explanation for the emergence of increased depression among
      pubertal girls and its persistence through adolescence.

PMID- 10078500
TI  - Obstetric complications and the risk of schizophrenia: a longitudinal study of a
      national birth cohort.
AB  - BACKGROUND: Numerous epidemiological studies found an increased risk of
      schizophrenia among persons exposed to various obstetric complications. The
      underlying mechanisms are unknown. OBJECTIVE: To study specific risk factors, as
      well as sets of risk factors, representing 3 different etiologic mechanisms: (1)
      malnutrition during fetal life; (2) extreme prematurity; and (3) hypoxia or
      ischemia. METHODS: In this longitudinal cohort study, information in the National
      Birth Register was linked to the National Inpatient Register. We followed up
      507516 children born between 1973 and 1977 with regard to a diagnosis of
      schizophrenia between 1987 and 1995 (238 cases). By record linkage, we also had
      access to data on psychiatric illness in the mother. Occurrence of schizophrenia
      was measured by the Mantel-Haenszel test and logistic regression. RESULTS: A
      number of specific risk factors were associated with an increased risk of
      schizophrenia. The relative risk (95% confidence interval) for preeclampsia was
      2.5 (1.4-4.5); vacuum extraction, 1.7 (1.1-2.6); and malformations, 2.4 (1.2
      5.1). In logistic regression models, we found that indicators of all 3 etiologic
      mechanisms were associated with increased point estimates of schizophrenia,
      although at lower risk levels. Preeclampsia, an indicator of fetal malnutrition,
      was the only risk factor with statistically significant increased risk after
      control for all potentially confounding factors. CONCLUSION: This study supports
      the theory of an association between obstetric complications and schizophrenia.
      Although preeclampsia was the strongest individual risk factor, there was
      evidence of increased risk associated with all 3 etiologic mechanisms.

PMID- 10078501
TI  - Predictors of relapse following response from a first episode of schizophrenia or
      schizoaffective disorder.
AB  - BACKGROUND: We examined relapse after response to a first episode of
      schizophrenia or schizoaffective disorder. METHODS: Patients with first-episode
      schizophrenia were assessed on measures of psychopathologic variables, cognition,
      social functioning, and biological variables and treated according to a
      standardized algorithm. The sample for the relapse analyses consisted of 104
      patients who responded to treatment of their index episode and were at risk for
      relapse. RESULTS: Five years after initial recovery, the cumulative first relapse
      rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse
      rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second
      relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%).
      Discontinuing antipsychotic drug therapy increased the risk of relapse by almost
      5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard
      ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses
      controlling for antipsychotic drug use showed that patients with poor premorbid
      adaptation to school and premorbid social withdrawal relapsed earlier. Sex,
      diagnosis, obstetric complications, duration of psychotic illness before
      treatment, baseline symptoms, neuroendocrine measures, methylphenidate
      hydrochloride challenge response, neuropsychologic and magnetic resonance imaging
      measures, time to response of the initial episode, adverse effects during
      treatment, and presence of residual symptoms after the initial episode were not
      significantly related to time to relapse. CONCLUSIONS: There is a high rate of
      relapse within 5 years of recovery from a first episode of schizophrenia and
      schizoaffective disorder. This risk is diminished by maintenance antipsychotic
      drug treatment.

PMID- 10078502
TI  - Abnormalities of cyclic adenosine monophosphate signaling in platelets from
      untreated patients with bipolar disorder.
AB  - BACKGROUND: Abnormalities in the cyclic adenosine monophosphate (cAMP)-dependent
      phosphorylation system have been recently reported in patients with bipolar
      disorder. We evaluated the immunoreactivity of the regulatory and catalytic
      subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its
      substrates, Rap1, in platelets from untreated euthymic, manic, and depressed
      patients with bipolar disorder and healthy subjects. METHODS: Platelets were
      collected from 112 drug-free patients with bipolar disorder (52 euthymic, 29
      depressed, and 31 manic) and 62 healthy subjects. The levels of cAMP-dependent
      protein kinase and Rap1 were assessed by Western blot analysis, immunostaining,
      and computer-assisted imaging. RESULTS: The immunolabeling of the catalytic
      subunit of cAMP-dependent protein kinase was significantly different among groups
      (P<.001), with higher values in untreated depressed and manic patients with
      bipolar disorder compared with untreated euthymic patients with bipolar disorder
      and healthy subjects. No significant differences were found in the immunolabeling
      of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase.
      The immunolabeling of Rap1 was significantly higher (P<.001) in untreated
      euthymic, depressed, and manic patients than in healthy persons. CONCLUSIONS:
      Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are
      altered in the platelets of bipolar patients. These findings may provide clues
      toward understanding the involvement of cAMP signaling in the pathogenesis of
      bipolar disorder.

PMID- 10078503
TI  - Brain magnetic resonance imaging of structural abnormalities in bipolar disorder.
AB  - BACKGROUND: The neuropathogenesis of bipolar disorder remains poorly described.
      Previous work suggests that patients with bipolar disorder may have abnormalities
      in neural pathways that are hypothesized to modulate human mood states. We
      examined differences in brain structural volumes associated with these pathways
      between patients with bipolar disorder hospitalized with mania and healthy
      community volunteers. METHODS: Twenty-four patients with bipolar disorder and
      mania were recruited from hospital admission records. Twenty-two healthy
      volunteers were recruited from the community who were similar to the patients in
      age, sex, race, height, handedness, and education. All subjects were scanned
      using a 3-dimensional radio-frequency-spoiled Fourier acquired steady state
      acquisition sequence on a 1.5-T magnetic resonance imaging scanner. Scans were
      analyzed using commercial software. Prefrontal, thalamic, hippocampal, amygdala,
      pallidal, and striatal volumetric measurements were compared between the 2
      groups. RESULTS: Patients with bipolar disorder demonstrated a significant (A =
      0.64; F6,37 = 3.4; P = .009) overall difference in structural volumes in these
      regions compared with controls. In particular, the amygdala was enlarged in the
      patients. Brain structural volumes were not significantly associated with
      duration of illness, prior medication exposure, number of previous hospital
      admissions, or duration of substance abuse. Separating patients into first
      episode (n = 12) and multiple-episode (n = 12) subgroups revealed no significant
      differences in any structure (P>.10). CONCLUSION: Patients with bipolar disorder
      exhibit structural abnormalities in neural pathways thought to modulate human
      mood.

PMID- 10078504
TI  - The temporal relationship between depressive symptoms and dementia: a community
      based prospective study.
AB  - BACKGROUND: The temporal relationship between the appearance of depressive
      symptoms and the clinical onset of dementia and Alzheimer disease was evaluated
      in a community sample. METHODS: An original sample of 1366 subjects aged 65 years
      or older, selected randomly from a rural Pennsylvania community, was cognitively
      screened at study entry and every 2 years thereafter. A subset of 954 survivors
      of this cohort without dementia was screened for depressive symptoms at the
      second and subsequent data-collection waves. A "depression cluster" was
      identified by the presence of 5 or more depressive symptoms, including depressed
      mood, at the time of screening. Cognitively impaired subjects and a sample of
      unimpaired controls underwent standardized clinical evaluation to determine the
      presence of incident dementia (by DSM-III-R criteria) and probable or possible
      Alzheimer disease (by criteria of the National Institute of Neurological and
      Communicative Disorders and Stroke and the Alzheimer's Disease and Related
      Disorders Association) and to estimate the clinical onset of dementia symptoms.
      RESULTS: A highly increased probability of the depression cluster developing
      existed among subjects following the onset of dementia (15.4% [6/39]) and
      Alzheimer disease (17.6% [6/34]) compared with subjects without dementia (3.2%
      [23/712]). The odds ratios, after adjustment for age, sex, education level, and
      self reported memory loss, for the development of depression were 6.5 (95%
      confidence interval, 2.2-19.1) in subjects with Alzheimer disease and 5.2 (95%
      confidence interval, 1.8-15.2) in subjects with overall dementia. Depressive
      symptoms did not confer a significantly increased relative risk of dementia
      (1.27; 95% confidence interval, 0.55-2.93) or Alzheimer disease (1.28; 95%
      confidence interval, 0.51-3.20). CONCLUSION: Depressive symptoms appeared to be
      early manifestations, rather than predictors, of Alzheimer disease in this
      community sample.

PMID- 10078505
TI  - Left temporal lobe dysfunction in schizophrenia: event-related potential and
      behavioral evidence from phonetic and tonal dichotic listening tasks.
AB  - BACKGROUND: Asymmetric reduction of the P3 event-related potential (ERP) has
      provided evidence of left temporal lobe dysfunction in schizophrenia. Prior
      studies have been limited by reliance on simple target detection (oddball) tasks
      with pure tones. This study investigated the time course and topography of ERPs
      to binaural syllables or complex tones in dichotic listening tasks. METHODS:
      Event-related potentials of 26 patients meeting criteria for schizophrenia (n =
      19) or schizoaffective disorder (n = 7) and 26 healthy controls were recorded
      from 30 scalp electrodes during 2 dichotic tasks in which different syllables or
      complex tones were simultaneously presented to each ear. A principal components
      analysis was used to derive factor scores corresponding to overlapping components
      in ERP waveforms--N1, N2, P3, and a late-positive potential. RESULTS: Healthy
      controls showed a right ear advantage for perceiving dichotic syllables, which
      was associated with greater N2 amplitude at left than right temporoparietal
      sites. Patients with schizophrenia did not show either this perceptual or N2
      asymmetry. Patients also had smaller late-positive potential amplitude when
      compared with controls for both syllables and complex tones, with greatest
      decrement over left temporal sites. CONCLUSIONS: A right ear advantage in healthy
      adults for perceiving consonant-vowels was associated with a left-lateralized ERP
      component peaking at 200 milliseconds after syllable onset (N2). Patients with
      schizophrenia failed to show either of these task-dependent asymmetries, which
      may indicate a dysfunction of left temporal regions involved in phonetic
      classification. A task-independent asymmetric reduction of a later positive
      potential in patients with schizophrenia resembled left temporal P3 reductions
      reported for auditory oddball tasks.

PMID- 10078506
TI  - Sensorimotor gating and thought disturbance measured in close temporal proximity
      in schizophrenic patients.
AB  - BACKGROUND: Sensorimotor gating abnormalities have been previously correlated
      with thought disturbance in schizophrenic patients. These correlative studies
      have led to the hypothesis that sensorimotor gating abnormalities may underlie
      thought disturbance. Several authors have cautioned, however, that this and
      similar hypotheses are supported by data recorded at different times or during
      resting states" and therefore incorrectly assume that the observed association
      represents a concurrent relationship. To address this issue, sensorimotor gating
      and thought disturbance were measured in close temporal proximity, thus
      strengthening the evidence for the association of these 2 abnormalities in
      schizophrenic patients. METHODS: Twenty-one schizophrenic men were assessed on
      measures of sensorimotor gating and thought disturbance. Sensorimotor gating was
      examined operationally via the use of prepulse inhibition. Thought disturbance
      was assessed via the Rorschach test measures of perceptual inaccuracy, disordered
      cognition, and the expression of normally repressed contents. Symptom rating
      scales (the Scale for the Assessment of Positive Symptoms and the alogia subscale
      of the Scale for the Assessment of Negative Symptoms) were also used. RESULTS:
      Deficient prepulse inhibition correlated significantly with 2 of the 3 Rorschach
      derived thought disturbance measures. Prepulse inhibition was not correlated
      significantly with symptom rating scales. The Rorschach measure of impaired
      perceptual accuracy independently accounted for 60% of the variance in prepulse
      inhibition measures and contributed 35% of the unique variance beyond the effect
      attributable to the Scale for the Assessment of Positive Symptoms. CONCLUSIONS:
      Assessment of information processing and thought disturbance measures in close
      temporal proximity resulted in strong evidence that gating deficits correlate
      highly with measures of perceptual and reasoning disturbances. This relationship
      may form an important basis for the cognitive dysfunction observed among
      schizophrenic patients.

PMID- 10078507
TI  - The Kobe earthquake and reduced suicide rate in Japanese males.

PMID- 10078508
TI  - Is a large body size during childhood a risk factor for later aggression?

PMID- 10078509
TI  - Population density and rehospitalization for the seriously and persistently
      mentally ill.

PMID- 10078510
TI  - Where next on misconduct?

PMID- 10078511
TI  - Anomalies in French blood inquiry over 'misleading' report.

PMID- 10078512
TI  - Indian budget boost targets innovation, vaccines and genetics.

PMID- 10078513
TI  - Collapse of talks on safety of GMO trade.

PMID- 10078514
TI  - South Africa stands firm on AIDS drug...

PMID- 10078515
TI  - Varmus wish list guides senators in fight for biomedical funding.

PMID- 10078516
TI  - Science comes to terms with the lessons of fraud.

PMID- 10078517
TI  - Japanese scandals raise public distrust.

PMID- 10078519
TI  - Papers vanish in mis-citation black hole.

PMID- 10078518
TI  - US stalls on new definitions of misconduct.

PMID- 10078520
TI  - Controversy over the cloning of mice.

PMID- 10078521
TI  - Forging links in an electronic paper chain.

PMID- 10078522
TI  - Space-grown crystals may prove their worth.

PMID- 10078523
TI  - An SH2 domain in disguise.

PMID- 10078524
TI  - Signal transduction. A taste of things to come.

PMID- 10078525
TI  - Immunology. Accessory to murder.

PMID- 10078526
TI  - Cell signalling. DREAM on without calcium.

PMID- 10078527
TI  - Using hair to screen for breast cancer.

PMID- 10078528
TI  - Change-blindness as a result of 'mudsplashes'.

PMID- 10078529
TI  - Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue:
      implications for nuclear transport.
AB  - The protein Ran is a small GTP-binding protein that binds to two types of
      effector inside the cell: Ran-binding proteins, which have a role in terminating
      export processes from the nucleus to the cytoplasm, and importin-beta-like
      molecules that bind cargo proteins during nuclear transport. The Ran-binding
      domain is a conserved sequence motif found in several proteins that participate
      in these transport processes. The Ran-binding protein RanBP2 contains four of
      these domains and constitutes a large part of the cytoplasmic fibrils that extend
      from the nuclear-pore complex. The structure of Ran bound to a non-hydrolysable
      GTP analogue (Ran x GppNHp) in complex with the first Ran-binding domain (RanBD1)
      of human RanBP2 reveals not only that RanBD1 has a pleckstrin-homology domain
      fold, but also that the switch-I region of Ran x GppNHp resembles the canonical
      Ras GppNHp structure and that the carboxy terminus of Ran is wrapped around
      RanBD1, contacting a basic patch on RanBD1 through its acidic end. This molecular
      'embrace' enables RanBDs to sequester the Ran carboxy terminus, triggering the
      dissociation of Ran x GTP from importin-beta-related transport factors and
      facilitating GTP hydrolysis by the GTPase-activating protein ranGAP. Such a
      mechanism represents a new type of switch mechanism and regulatory protein
      protein interaction for a Ras-related protein.

PMID- 10078530
TI  - Dissociation of dopamine release in the nucleus accumbens from intracranial self
      stimulation.
AB  - Mesolimbic dopamine-releasing neurons appear to be important in the brain reward
      system. One behavioural paradigm that supports this hypothesis is intracranial
      self-stimulation (ICS), during which animals repeatedly press a lever to
      stimulate their own dopamine-releasing neurons electrically. Here we study
      dopamine release from dopamine terminals in the nucleus accumbens core and shell
      in the brain by using rapid-responding voltammetric microsensors during
      electrical stimulation of dopamine cell bodies in the ventral tegmental
      area/substantia nigra brain regions. In rats in which stimulating electrode
      placement failed to elicit dopamine release in the nucleus accumbens, ICS
      behaviour was not learned. In contrast, ICS was acquired when stimulus trains
      evoked extracellular dopamine in either the core or the shell of the nucleus
      accumbens. In animals that could learn ICS, experimenter-delivered stimulation
      always elicited dopamine release. In contrast, extracellular dopamine was rarely
      observed during ICS itself. Thus, although activation of mesolimbic dopamine
      releasing neurons seems to be a necessary condition for ICS, evoked dopamine
      release is actually diminished during ICS. Dopamine may therefore be a neural
      substrate for novelty or reward expectation rather than reward itself.

PMID- 10078531
TI  - Regulation of calcium signalling in T lymphocytes by the second messenger cyclic
      ADP-ribose.
AB  - Cyclic ADP-ribose (cADPR) is a natural compound that mobilizes calcium ions in
      several eukaryotic cells. Although it can lead to the release of calcium ions in
      T lymphocytes, it has not been firmly established as a second messenger in these
      cells. Here, using high-performance liquid chromatography analysis, we show that
      stimulation of the T-cell receptor/CD3 (TCR/CD3) complex results in activation of
      a soluble ADP-ribosyl cyclase and a sustained increase in intracellular levels of
      cADPR. There is a causal relation between increased cADPR concentrations,
      sustained calcium signalling and activation of T cells, as shown by inhibition of
      TCR/CD3-stimulated calcium signalling, cell proliferation and expression of the
      early- and late-activation markers CD25 and HLA-DR by using cADPR antagonists.
      The molecular target for cADPR, the type-3 ryanodine receptor/calcium channel, is
      expressed in T cells. Increased cADPR significantly and specifically stimulates
      the apparent association of [3H]ryanodine with the type-3 ryanodine receptor,
      indicating a direct modulatory effect of cADPR on channel opening. Thus we show
      the presence, causal relation and biological significance of the major
      constituents of the cADPR/calcium-signalling pathway in human T cells.

PMID- 10078532
TI  - Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic
      acinar cells.
AB  - Many hormones and neurotransmitters evoke Ca2+ release from intracellular stores,
      often triggering agonist-specific signatures of intracellular Ca2+ concentration.
      Inositol trisphosphate (InsP3) and cyclic adenosine 5'-diphosphate-ribose (cADPR)
      are established Ca2+-mobilizing messengers that activate Ca2+ release through
      intracellular InsP3 and ryanodine receptors, respectively. However, in pancreatic
      acinar cells, neither messenger can explain the complex pattern of Ca2+ signals
      triggered by the secretory hormone cholecystokinin (CCK). We show here that the
      Ca2+-mobilizing molecule nicotinic acid adenine dinucleotide phosphate (NAADP),
      an endogenous metabolite of beta-NADP, triggers a Ca2+ response that varies from
      short-lasting Ca2+ spikes to a complex mixture of short-lasting (1-2s) and long
      lasting (0.2-1 min) Ca2+ spikes. Cells were significantly more sensitive to NAADP
      than to either cADPR or InsP3, whereas higher concentrations of NAADP selectively
      inactivated CCK-evoked Ca2+ signals in pancreatic acinar cells, indicating that
      NAADP may function as an intracellular messenger in mammalian cells.

PMID- 10078533
TI  - Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires
      presentation of exogenous antigen.
AB  - Cytotoxic T lymphocytes (CTLs) are thought to detect viral infections by
      monitoring the surface of all cells for the presence of viral peptides bound to
      major histocompatibility complex (MHC) class I molecules. In most cells, peptides
      presented by MHC class I molecules are derived exclusively from proteins
      synthesized by the antigen-bearing cells. Macrophages and dendritic cells also
      have an alternative MHC class I pathway that can present peptides derived from
      extracellular antigens; however, the physiological role of this process is
      unclear. Here we show that virally infected non-haematopoietic cells are unable
      to stimulate primary CTL-mediated immunity directly. Instead, bone-marrow-derived
      cells are required as antigen-presenting cells (APCs) to initiate anti-viral CTL
      responses. In these APCs, the alternative (exogenous) MHC class I pathway is the
      obligatory mechanism for the initiation of CTL responses to viruses that infect
      only non-haematopoietic cells.

PMID- 10078534
TI  - DREAM is a Ca2+-regulated transcriptional repressor.
AB  - Fluxes in amounts of intracellular calcium ions are important determinants of
      gene expression. So far, Ca2+-regulated kinases and phosphatases have been
      implicated in changing the phosphorylation status of key transcription factors
      and thereby modulating their function. In addition, direct effectors of Ca2+
      induced gene expression have been suggested to exist in the nucleus, although no
      such effectors have been identified yet. Expression of the human prodynorphin
      gene, which is involved in memory acquisition and pain, is regulated through its
      downstream regulatory element (DRE) sequence, which acts as a location-dependent
      gene silencer. Here we isolate a new transcriptional repressor, DRE-antagonist
      modulator (DREAM), which specifically binds to the DRE. DREAM contains four Ca2+
      binding domains of the EF-hand type. Upon stimulation by Ca2+, DREAM's ability to
      bind to the DRE and its repressor function are prevented. Mutation of the EF
      hands abolishes the response of DREAM to Ca2+. In addition to the prodynorphin
      promoter, DREAM represses transcription from the early response gene c-fos. Thus,
      DREAM represents the first known Ca2+-binding protein to function as a DNA
      binding transcriptional regulator.

PMID- 10078535
TI  - Structure of the amino-terminal domain of Cbl complexed to its binding site on
      ZAP-70 kinase.
AB  - Cbl is an adaptor protein that functions as a negative regulator of many
      signalling pathways that start from receptors at the cell surface. The
      evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to
      phosphorylated tyrosine residues and has cell-transforming activity. Point
      mutations in Cbl that disrupt its recognition of phosphotyrosine also interfere
      with its negative regulatory function and, in the case of v-cbl, with its
      oncogenic potential. In T cells, Cbl-N binds to the tyrosine-phosphorylated
      inhibitory site of the protein tyrosine kinase ZAP-70. Here we describe the
      crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that
      represents its binding site in ZAP-70. The structures show that Cbl-N is composed
      of three interacting domains: a four-helix bundle (4H), an EF-hand calcium
      binding domain, and a divergent SH2 domain that was not recognizable from the
      amino-acid sequence of the protein. The calcium-bound EF hand wedges between the
      4H and SH2 domains and roughly determines their relative orientation. In the
      ligand-occupied structure, the 4H domain packs against the SH2 domain and
      completes its phosphotyrosine-recognition pocket. Disruption of this binding to
      ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2
      domains confirms that the three domains together form an integrated
      phosphoprotein-recognition module.

PMID- 10078536
TI  - Cardiovascular data on sildenafil citrate: introduction.

PMID- 10078537
TI  - Tissue distribution of phosphodiesterase families and the effects of sildenafil
      on tissue cyclic nucleotides, platelet function, and the contractile responses of
      trabeculae carneae and aortic rings in vitro.
AB  - Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), which has
      been shown to be a clinically effective treatment for erectile dysfunction. Its
      action results from increased levels of cyclic guanosine monophosphate (cGMP),
      which is normally degraded by PDE5. This cyclic nucleotide is a second messenger
      for nitric oxide, which is involved in the regulation of numerous functions,
      including vascular smooth muscle tone. In an attempt to better predict the
      effects of sildenafil on cardiovascular function, the distribution of PDE
      activity was determined with anti-PDE1 and anti-PDE5 antibodies in the human
      cardiac ventricle and saphenous vein, and in vitro studies were performed on the
      isolated human cardiac ventricle, corpus cavernosum, saphenous vein, and
      mesenteric artery as well as on rabbit aorta, dog coronary artery, dog trabecular
      tissue, and rabbit and human platelets. The major PDE activity in the human
      cardiac ventricle was shown to be calcium/calmodulin-dependent PDE1, but there
      was no detectable level of PDE5. In contrast, the human saphenous vein contained
      PDEs 1, 4, and 5, and the human mesenteric artery contained PDEs 1, 2, 3, 4, and
      5. The distribution of PDE5 in the cardiovascular system is consistent with the
      observed pharmacodynamic and clinical effects of sildenafil. Sildenafil, unlike
      milrinone, a selective PDE3 inhibitor, had no effect on the isolated trabeculae
      carneae; this is consistent with the lack of PDE5 expression in cardiac myocytes.
      Sildenafil selectively increased cGMP levels in coronary vascular smooth muscle
      tissue but produced no change in cyclic adenosine monophosphate (cAMP) levels,
      which is consistent with the drug's selectivity for PDE5. In phenylephrine
      contracted isolated rabbit aortic rings, sildenafil enhanced the relaxation
      induced by the nitric oxide donor glyceryl trinitrate, suggesting that sildenafil
      may potentiate the hypotensive effects of nitric oxide donor agents on the
      vasculature, an effect that has been observed clinically. Human platelets were
      found to contain PDE5, which was inhibited by 50% (IC50) by sildenafil at a
      concentration of 6.3 nM, consistent with the IC50 value in the corpus cavernosum.
      Sildenafil alone had no direct effect on platelet function, but it potentiated
      the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human
      platelets. The pharmacodynamic and adverse event profiles observed in clinical
      trials with sildenafil are consistent with the in vitro profile of the tissue
      distribution of PDE5 and its known mechanism of action as a selective inhibitor
      of PDE5.

PMID- 10078538
TI  - Effects of sildenafil citrate on human hemodynamics.
AB  - Nitric oxide (NO) induces the formation of intracellular cyclic guanosine
      monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits
      phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of
      the penis, effectively blocks the degradation of cGMP and enhances erectile
      function in men with erectile dysfunction. The NO-cGMP pathway also plays an
      important role in mediating blood pressure. It is, therefore, possible that the
      therapeutic doses of sildenafil used to treat erectile dysfunction may have
      clinically significant effects on human hemodynamics. Three studies were
      undertaken to assess the effects of intravenously, intra-arterially, and orally
      administered doses of sildenafil on blood pressure, heart rate, cardiac output,
      and forearm blood flow and venous compliance in healthy men. A fourth study
      evaluated the hemodynamic effects of intravenous sildenafil in men with stable
      ischemic heart disease. In healthy men, significant (p <0.01) decreases in supine
      systolic and diastolic blood pressures were observed with intravenous sildenafil
      (20, 40, and 80 mg) at the end of the infusion period when plasma levels of
      sildenafil were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm
      Hg, for the 40- and 80-mg doses, respectively). These changes were transient and
      not dose related. Modest reductions in systemic vascular resistance also were
      observed (maximum decrease 16%), although heart rate was not affected by
      sildenafil administration when compared with placebo. Single oral doses of
      sildenafil (100, 150, and 200 mg) produced no significant changes in cardiac
      index from 1-12 hours postdose between placebo- and sildenafil-treated subjects.
      The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg.
      The 80-mg intravenous dose and the 200-mg oral dose of sildenafil produced
      comparable plasma levels at twice the maximum therapeutic dose (recommended
      range, 25-100 mg). After brachial artery infusion of sildenafil (up to 300
      microg/min), there was a modest vasodilation of resistance arteries and a
      reversal of norepinephrine-induced preconstriction of forearm veins. These
      hemodynamic effects were similar to but smaller in magnitude than those of
      nitrates. In a small pilot study of men with ischemic heart disease, decreases
      from baseline in pulmonary arterial pressure (-27% at rest and -19% during
      exercise) and cardiac output (-7% at rest and -11% during exercise) were observed
      after 40-mg intravenous doses of sildenafil. Sildenafil was well tolerated by
      subjects and patients in all studies, with headache and other symptoms of
      vasodilation the most commonly reported adverse effects of treatment. Modest,
      transient hemodynamic changes were observed in healthy men after single
      intravenous or oral doses of sildenafil even at supratherapeutic doses. In men
      with stable ischemic heart disease, sildenafil produced modest effects on
      hemodynamic parameters at rest and during exercise.

PMID- 10078539
TI  - Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction
      studies with an organic nitrate and a calcium antagonist.
AB  - Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)
      specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly
      effective treatment for erectile dysfunction. The mechanism of action of
      sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during
      sexual stimulation, which results in corpus cavernosal smooth muscle relaxation
      and penile erection. Endogenously derived NO is also involved in blood pressure
      regulation through its effect on basal vascular tone, which is mediated by cGMP
      levels. Organic nitrates and NO donors exert their therapeutic effects on blood
      pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since
      both sildenafil and organic nitrates exert their pharmacologic effects via
      increases in cGMP concentrations, a double-blind, placebo-controlled, crossover
      study was undertaken to investigate the effects of sildenafil coadministered with
      glyceryl trinitrate on blood pressure and heart rate in healthy male subjects.
      The hemodynamic effects of sildenafil were also evaluated in a second placebo
      controlled crossover study in men with hypertension who were taking the calcium
      antagonist amlodipine, which has a mechanism of action that does not involve the
      cGMP pathway. In the first crossover study, subjects were treated with oral
      sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on
      day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate
      (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and
      doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking
      sildenafil or placebo. On day 5, subjects received a sublingual glyceryl
      trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or
      placebo. During sildenafil treatment, the subjects were significantly less
      tolerant of intravenously administered glyceryl trinitrate than during placebo
      treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or
      the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl
      trinitrate tablet was administered on day 5, a 4-fold greater decrease in
      systolic blood pressure was observed for the subjects during the sildenafil
      treatment period than during the placebo treatment period. The changes in heart
      rate were negligible during both glyceryl trinitrate challenges. In conclusion,
      sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic
      nitrate. Thus, sildenafil administration to patients who are using organic
      nitrates, either regularly and/or intermittently, in any form is contraindicated.
      In the second crossover study, men with hypertension, who were taking 5 or 10
      mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or
      placebo. Coadministration of sildenafil did not significantly affect the
      pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the
      mean maximum change from baseline in supine systolic and diastolic blood
      pressures between the sildenafil plus amlodipine and the placebo plus amlodipine
      treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The
      mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus
      amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine
      treatment (p <0.02). The adverse events in this study were predominantly mild or
      moderate and did not cause discontinuation of treatment. Adverse events
      considered to be related to sildenafil treatment included headache, nausea, and
      dyspepsia. In patients with hypertension who were taking amlodipine therapy,
      sildenafil produced additive, but not synergistic, reductions in blood pressure.
      The difference in the mean maximum change from baseline in blood pressure between
      sildenafil plus amlodipine and placebo plus amlodipine was comparable to the
      decrease in blood pressure reported for healthy men taking sildenafil alone.
      (ABSTRACT TRUNCATED)

PMID- 10078540
TI  - Efficacy and safety of sildenafil citrate in the treatment of erectile
      dysfunction in patients with ischemic heart disease.
AB  - Erectile dysfunction is a common condition in men with cardiovascular disease,
      probably as a result of shared factors that impair hemodynamic mechanisms in the
      penile and ischemic vasculature. Sildenafil citrate, an orally active, selective
      inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy
      and safety profiles in men with erectile dysfunction of various etiologies.
      Sildenafil administration is contraindicated in patients who are taking nitrates
      or nitric oxide donors. This retrospective subanalysis of data from double-blind,
      placebo-controlled studies assessed the efficacy (9 studies) and safety (11
      studies) of sildenafil in patients with erectile dysfunction and ischemic heart
      disease who were not taking nitrates. Of 3,672 patients randomized to receive
      sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo
      controlled studies, 357 (10%) reported a history (past or present) of ischemic
      heart disease and were not taking nitrates. Efficacy was assessed using end-of
      treatment responses to Question 3 (ability to achieve an erection) and Question 4
      (ability to maintain an erection) of the International Index of Erectile Function
      (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF
      (erectile function, orgasmic function, sexual desire, intercourse satisfaction,
      and overall satisfaction), and responses to a global efficacy question ("Did the
      treatment improve your erections?"). The responses to the 2 IIEF questions were
      graded on a scale of 1 (almost never or never) to 5 (almost always or always),
      with a score of 0 indicating no attempt at sexual intercourse. At the end of
      treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients
      with erectile dysfunction and ischemic heart disease were significantly higher
      for the sildenafil group than for the placebo group (p <0.0001). Mean end-of
      treatment scores for the IIEF domains also demonstrated significant increases for
      sildenafil-treated patients compared with those receiving placebo (p <0.05). At
      the end of treatment, improved erections were reported by 70% of patients who
      received sildenafil and by 20% of those in the placebo group p <0.0001). For the
      sildenafil group, the incidences of the most common adverse events (headache 25%,
      flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were
      similar to those in patients without this concomitant illness (21%, 15%, and 10%,
      respectively). Moreover, the overall incidence of cardiovascular adverse events
      other than flushing was comparable in patients with and without ischemic heart
      disease for both treatment groups. Since there is a degree of cardiac risk
      associated with sexual activity, clinicians should consider the patient's
      cardiovascular status before initiating any treatment for erectile dysfunction.
      Physicians should be aware that patients with underlying cardiovascular disease
      could be adversely affected by the vasodilator effects of sildenafil, especially
      in combination with sexual activity. The results of the present subanalysis
      indicate that oral sildenafil significantly improves erectile function and is
      well tolerated in patients with erectile dysfunction and ischemic heart disease
      who are not taking nitrate therapy.

PMID- 10078541
TI  - Overall cardiovascular profile of sildenafil citrate.
AB  - Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the
      first in a new class of orally effective treatments for erectile dysfunction.
      During sexual stimulation, the cavernous nerves release nitric oxide (NO), which
      induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle
      relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process
      during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of
      cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood
      pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is
      unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic
      circulation but at different points along the NO-cGMP pathway. The combination is
      contraindicated because they synergistically potentiate vasodilation and may
      cause excessive reductions in blood pressure. Erectile dysfunction is a
      significant medical condition that shares numerous risk factors with ischemic
      heart disease, and hence a substantial overlap exists between these patient
      groups. From extensive clinical trials, the most commonly reported cardiovascular
      adverse events in patients treated with sildenafil were headache (16%), flushing
      (10%), and dizziness (2%). The incidences of hypotension, orthostatic
      hypotension, and syncope and the rate of discontinuation of treatment due to
      adverse events were <2% and were the same in patients taking sildenafil and those
      taking placebo. Retrospective analysis of the concomitant use of antihypertensive
      medications (beta blockers, alpha blockers, diuretics, angiotensin-converting
      enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not
      indicate an increase in the reports of adverse events or significant episodes of
      hypotension compared with patients treated with sildenafil alone. In clinical
      trials, the incidence of serious cardiovascular adverse events, including stroke
      and myocardial infarction, was the same for patients treated with sildenafil or
      placebo. Concurrent disease states, such as renal or hepatic impairment, or
      concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could
      increase systemic exposure to sildenafil. Since the US market launch in April
      1998, monitoring of spontaneous adverse event reports in association with
      sildenafil has demonstrated a pattern that is generally consistent with the
      experience observed during clinical development, with the exception of infrequent
      reports of priapism. In conclusion, extensive clinical testing has shown that
      overall treatment with sildenafil for up to 1 year is well tolerated and is
      associated with a low incidence of adverse events that result in discontinuation
      of treatment in <3% of patients.

PMID- 10078542
TI  - Is blood glucose predictable from previous values? A solicitation for data.
AB  - An important question about blood glucose control in diabetes is, Can present and
      future blood glucose values be predicted from recent blood glucose history? If
      this is possible, new continuous blood glucose monitoring technologies under
      development may lead to qualitatively better therapeutic capabilities. Not only
      could continuous monitoring technologies alert a user when a hypoglycemic episode
      or other blood glucose excursion is underway, but measurements may also provide
      sufficient information to predict near-future blood glucose values. A predictive
      capability based only on recent blood glucose history would be advantageous
      because there would be no need to involve models of glucose and insulin
      distribution, with their inherent requirement for detailed accounting of vascular
      glucose loads and insulin availability. Published data analyzed here indicate
      that blood glucose dynamics are not random, and that blood glucose values can be
      predicted, at least for the near future, from frequently sampled previous values.
      Data useful in further exploring this concept are limited, however, and an appeal
      is made for collection of more.

PMID- 10078543
TI  - Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin
      secretion.
AB  - Modulation of lipoprotein lipase (LPL) allows a tissue-specific partitioning of
      triglyceride-derived fatty acids, and insulin is a major modulator of its
      activity. The present studies were aimed to assess in rats the contribution of
      insulin to the response of adipose tissue and muscle LPL to food intake.
      Epididymal and retroperitoneal adipose LPL rose 65% above fasting values as early
      as 1 h after the onset of a 30-min high-carbohydrate meal, with a second activity
      peak 1 h later that was maintained for an additional 2 h. Soleus muscle LPL was
      decreased by 25% between 0.5 and 4 h after meal intake. The essential
      contribution of insulin to the LPL response to food intake was determined by
      preventing the full insulin response to meal intake by administration of
      diazoxide (150 mg/kg body wt, in the meal). The usual postprandial changes in
      adipose and muscle LPL did not occur in the absence of an increase in
      insulinemia. However, the early (60 min) increase in adipose tissue LPL was not
      prevented by the drug, likely because of the maintenance of the early centrally
      mediated phase of insulin secretion. In a subsequent study, rats chronically
      implanted with a gastric cannula were used to demonstrate that the postprandial
      rise in adipose LPL is independent of nutrient absorption and can be elicited by
      the cephalic (preabsorptive) phase of insulin secretion. Obese Zucker rats were
      used because of their strong cephalic insulin response. After an 8-h fast, rats
      were fed a liquid diet ad libitum (orally, cannula closed), sham fed (orally,
      cannula opened), or fed directly into the stomach via the cannula during 4 h.
      Insulinemia increased 10-fold over fasting levels in ad libitum- and intragastric
      fed rats and threefold in sham-fed rats. Changes in adipose tissue LPL were
      proportional to the elevation in plasma insulin levels, demonstrating that the
      cephalic-mediated rise in insulinemia, in the absence of nutrient absorption,
      stimulates adipose LPL. These results demonstrate the central role of insulin in
      the postprandial response of tissue LPL, and they show that cephalically mediated
      insulin secretion is able to stimulate adipose LPL.

PMID- 10078544
TI  - Autoantibody appearance and risk for development of childhood diabetes in
      offspring of parents with type 1 diabetes: the 2-year analysis of the German
      BABYDIAB Study.
AB  - The temporal development of autoantibodies was studied in 1,353 offspring of
      parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to
      insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9
      months, 2 years, and 5 years of age. At birth, no offspring had islet
      autoimmunity other than maternally acquired antibodies, which were shown to
      influence antibody prevalence up to age 6 months. Antibodies detected thereafter
      were likely to represent a true de novo production, since prevalences were the
      same for offspring from mothers and fathers with diabetes, antibodies detected at
      9 months were almost always confirmed in the 2-year sample and were associated
      with an increased likelihood of having or developing other antibodies. By 2 years
      of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one
      autoantibody. IAAs were detected most frequently, and few had autoantibodies in
      the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs
      preceded other antibodies in 10 cases and were first detected concurrently with
      other antibodies in 12 and after detection of other antibodies in 1. Development
      of additional antibodies and changes in levels, including decline of IAAs at
      older age, was frequent. Nine children, all with IAAs and ICAs, developed
      diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI
      0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody
      in their 2-year sample. Autoimmunity associated with childhood diabetes is an
      early event and a dynamic process. Presence of IAAs is a consistent feature of
      this autoimmunity, and IAA detection can identify children at risk.

PMID- 10078545
TI  - Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4,
      DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice.
AB  - The 65KD isoform of GAD is considered to be a major target autoantigen in many
      humans with autoimmune prediabetes or diabetes. The major histocompatibility
      complex class II allele DQA1*0301, DQB1*0302, which encodes HLA-DQ8, confers
      susceptibility to type 1 diabetes and occurs in up to 80% of affected
      individuals. To map T-cell epitopes for GAD65 restricted to the diabetes
      associated DQ8 heterodimer, we generated transgenic NOD mice expressing HLA-DQ8
      and human CD4 while having the mouse class II gene (IA(beta)) deleted. These mice
      were immunized with full-length purified recombinant GAD65, and the fine
      specificity of T-cell responses was mapped by examining recall responses of bulk
      splenocytes to an overlapping set of 20-mer peptides encompassing the entire
      GAD65 protein. Four different peptides (P121-140, P201-220, P231-250, and P471
      490) gave significant T-cell recall responses. P201-220 and P231-250 have been
      shown previously to bind DQ8, whereas the other two peptides had been classified
      as nonbinders. Interestingly, the peptide giving the greatest response (P201-220)
      encompasses residues 206-220 of GAD65, a region that has been shown to be a
      dominant T-cell epitope in wild-type IA(g7) NOD mice. Overlap in this T-cell
      epitope likely reflects structural similarities between DQ8 and IA(g7). The fine
      specificity of antibody responses in the GAD65-immunized mice was also examined
      by testing the antisera by enzyme-linked immunosorbent assay (ELISA) against the
      same overlapping set of peptides. The two dominant B-cell epitopes were P361-380
      and P381-400; P121-140 and P471-490 appeared to correspond to both B- and T-cell
      epitopes. Although the NOD human CD4, DQ8, IA(null) transgenic mice generated in
      these studies do not develop autoimmune diabetes either spontaneously or after
      cyclophosphamide treatment, they can be used to map DQ8-restricted T-cell
      epitopes for a variety of human islet autoantigens. They can also be used to test
      T-cell-specific reagents, such as fluorescently labeled DQ8 tetramers containing
      GAD65 peptides or other beta-cell peptides, which we believe will be useful in
      analyzing human immune responses in diabetic and prediabetic patients.

PMID- 10078546
TI  - Essential role of caspase-3 in apoptosis of mouse beta-cells transfected with
      human Fas.
AB  - Several recent studies have indicated that the Fas-Fas ligand system may be
      critical for pancreatic beta-cell destruction in type 1 diabetes. Although the
      fundamental roles of caspases in the mammalian apoptotic machinery have been
      elucidated, it is not known which caspase or caspases play a major role in Fas
      mediated apoptosis of beta-cells. In this study, we transfected human Fas cDNA
      into a mouse beta-cell line (betaTC1) and established a beta-cell clone
      expressing human Fas. This clone, designated hFas/betaTC1, underwent apoptosis
      when exposed to anti-Fas, showing hallmarks of apoptosis (chromatin condensation,
      nucleolar disintegration, internucleosomal DNA fragmentation, and annexin V
      staining), indicating that the mouse beta-cell line has the intact machinery of
      Fas-mediated apoptosis. The cross-linking of Fas by anti-Fas resulted in the
      elevation of caspase-3-like, but not caspase-1-like, protease activity 2-12 h
      after the addition of the anti-Fas. A caspase-3 inhibitor, Z-Asp-Glu-Val-Asp
      fluoromethyl ketone, attenuated the Fas-mediated beta-cell apoptosis, while a
      caspase-1 inhibitor, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, failed to
      suppress the apoptosis. Thus the Fas-induced death signal apparently bypassed
      caspase-1 in the cells. Furthermore, an antisense caspase-3 construct blocked
      caspase-3 activation and substantially suppressed Fas-triggered apoptosis of
      hFas/betaTC1 cells. These observations suggest the essential role of caspase-3 in
      Fas-mediated apoptosis of the beta-cell line.

PMID- 10078547
TI  - Auto- and alloimmune reactivity to human islet allografts transplanted into type
      1 diabetic patients.
AB  - Allogeneic islet transplantation can restore an insulin-independent state in C
      peptide-negative type 1 diabetic patients. We recently reported three cases of
      surviving islet allografts that were implanted in type 1 diabetic patients under
      maintenance immune suppression for a previous kidney graft. The present study
      compares islet graft-specific cellular auto- and alloreactivity in peripheral
      blood from those three recipients and from four patients with failing islet
      allografts measured over a period of 6 months after portal islet implantation.
      The three cases that remained C-peptide-positive for >1 year exhibited no signs
      of alloreactivity, and their autoreactivity to islet autoantigens was only
      marginally increased. In contrast, rapid failure (<3 weeks) in three other cases
      was accompanied by increases in precursor frequencies of graft-specific
      alloreactive T-cells; in one of them, the alloreactivity was preceded by a
      sharply increased autoreactivity to several islet autoantigens. One recipient had
      a delayed loss of islet graft function (33 weeks); he did not exhibit signs of
      graft-specific alloimmunity, but developed a delayed increase in autoreactivity.
      The parallel between metabolic outcome of human beta-cell allografts and cellular
      auto- and alloreactivity in peripheral blood suggests a causal relationship. The
      present study therefore demonstrates that T-cell reactivities in peripheral blood
      can be used to monitor immune mechanisms, which influence survival of beta-cell
      allografts in diabetic patients.

PMID- 10078548
TI  - The mechanism of islet amyloid polypeptide toxicity is membrane disruption by
      intermediate-sized toxic amyloid particles.
AB  - NIDDM is characterized by islet amyloid deposits and decreased beta-cell mass.
      Islet amyloid is derived from the locally expressed protein islet amyloid
      polypeptide (IAPP). While it is now widely accepted that abnormal aggregation of
      IAPP has a role in beta-cell death in NIDDM, the mechanism remains unknown. We
      hypothesized that small IAPP aggregates, rather than mature large amyloid
      deposits, are cytotoxic. Consistent with this hypothesis, freshly dissolved human
      (h)-IAPP was cytotoxic when added to dispersed mouse and human islet cells,
      provoking the formation of abnormal vesicle-like membrane structures in
      association with vacuolization and cell death. Human islet cell death occurred by
      both apoptosis and necrosis, predominantly between 24 and 48 h after exposure to
      h-IAPP. In contrast, the addition to dispersed islet cells of matured h-IAPP
      containing large amyloid deposits of organized fibrils was seldom associated with
      vesicle-like structures or features of cell death, even though the cells were
      often encased in the larger amyloid deposits. Based on these observations, we
      hypothesized that h-IAPP cytotoxicity is mediated by membrane damage induced by
      early h-IAPP aggregates. Consistent with this hypothesis, application of freshly
      dissolved h-IAPP to voltage-clamped planar bilayer membranes (a cell-free in
      vitro system) also caused membrane instability manifested as a marked increase in
      conductance, increased membrane electrical noise, and accelerated membrane
      breakage, effects that were absent using matured h-IAPP or rat IAPP solutions.
      Light-scattering techniques showed that membrane toxicity corresponded to h-IAPP
      aggregates containing approximately 25-6,000 IAPP molecules, an intermediate
      sized amyloid particle that we term intermediate-sized toxic amyloid particles
      (ISTAPs). We conclude that freshly dissolved h-IAPP is cytotoxic and that this
      cytotoxicity is mediated through an interaction of ISTAPs with cellular
      membranes. Once ISTAPs mature into amyloid deposits comprising >10(6) molecules,
      the capacity of h-IAPP to cause membrane instability and islet cell death is
      significantly reduced or abolished. These data may have implications for the
      mechanism of cell death in other diseases characterized by local amyloid
      formation (such as Alzheimer's disease).

PMID- 10078549
TI  - Site-specific phosphorylation of synapsin I by Ca2+/calmodulin-dependent protein
      kinase II in pancreatic betaTC3 cells: synapsin I is not associated with insulin
      secretory granules.
AB  - Increasing evidence supports a physiological role of Ca2+/calmodulin-dependent
      protein kinase II (CaM kinase II) in the secretion of insulin from the pancreatic
      beta-cell, but the precise sites of action are not known. A role of this enzyme
      in neuroexocytosis is implicated by its phosphorylation of a vesicle-associated
      protein, synapsin I. Because of emerging similarities to the neuron with respect
      to exocytotic mechanisms, the expression and phosphorylation of synapsin I in the
      beta-cell have been studied. Synapsin I expression in clonal mouse beta-cells
      (betaTC3) and primary rat islet beta-cells was initially confirmed by immunoblot
      analysis. By immunoprecipitation, in situ phosphorylation of synapsin I was
      induced in permeabilized betaTC3 cells within a Ca2+ concentration range shown to
      activate endogenous CaM kinase II under identical conditions. Proteolytic digests
      of these immunoprecipitates revealed that calcium primarily induced the increased
      phosphorylation of sites identified as CaM kinase II-specific and distinct from
      protein kinase A-specific sites. Immunofluorescence and immunogold electron
      microscopy verified synapsin I expression in betaTC3 cells and pancreatic slices
      but demonstrated little if any colocalization of synapsin I with insulin
      containing dense core granules. Thus, although this study establishes that
      synapsin I is a substrate for CaM kinase II in the pancreatic beta-cell, this
      event appears not to be important for the mobilization of insulin granules.

PMID- 10078550
TI  - The homeodomain protein IDX-1 increases after an early burst of proliferation
      during pancreatic regeneration.
AB  - Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that
      transactivates the insulin promoter, has been shown by targeted gene ablation to
      be required for pancreatic development. After 90% pancreatectomy (Px), the adult
      pancreas regenerates in a process recapitulating embryonic development, starting
      with a burst of proliferation in the epithelium of the common pancreatic duct. In
      this model, IDX-1 mRNA was detected by semiquantitative reverse transcription
      polymerase chain reaction in total RNA from isolated common pancreatic ducts at
      levels 10% of those of isolated islets. The IDX-1 mRNA levels were not
      significantly different for common pancreatic ducts of Px, sham Px, and
      unoperated rats and did not change with time after surgery. By immunoblot
      analysis, IDX-1 protein was only faintly detected in these ducts 1 and 7 days
      after Px or sham Px but was easily detected at 2 and 3 days after Px. Similarly,
      IDX-1 immunostaining was barely detectable in sham or unoperated ducts but was
      strong in ducts at 2-3 days after Px. The increase of IDX-1 immunostaining
      followed that of BrdU incorporation (proliferation). These results indicate a
      posttranscriptional regulation of the IDX-1 expression in ducts. In addition,
      islets isolated 3-7 d after Px showed higher IDX-1 protein expression than
      control islets. Thus, in pancreatic regeneration IDX-1 is upregulated in newly
      divided ductal cells as well as in islets. The timing of enhanced expression of
      IDX-1 implies that IDX-1 is not important in the initiation of regeneration but
      may be involved in the differentiation of ductal cells to beta-cells.

PMID- 10078551
TI  - Metabolic regulation, activity state, and intracellular binding of glucokinase in
      insulin-secreting cells.
AB  - Regulation of glucose-induced insulin secretion is crucially dependent on
      glucokinase function in pancreatic beta-cells. Glucokinase mRNA expression was
      metabolically regulated allowing continuous translation into enzyme protein.
      Glucokinase enzyme activity in the beta-cell was exclusively regulated by
      glucose. Using a selective permeabilization technique, different intracellular
      activity states of the glucokinase enzyme in bioengineered glucokinase
      overexpressing RINm5F tissue culture cells were observed. These results could be
      confirmed in analogous experiments with dispersed islet cells. A diffusible
      glucokinase fraction with high enzyme activity could be distinguished from an
      intracellularly bound fraction with low activity. Glucose induced a significant
      long-term increase of the active glucokinase fraction. This effect was
      accomplished through the release of glucokinase enzyme protein from an
      intracellular binding site of protein character. The inhibitory function of this
      protein factor was abolished through proteolytic digestion or heat inactivation.
      Northern blot analyses revealed that this binding protein was not identical to
      the well-known liver glucokinase regulatory protein. This hitherto unknown new
      protein factor may have the function of a glucokinase regulatory protein in the
      pancreatic beta-cell, which may regulate glucokinase enzyme activity in a glucose
      dependent manner.

PMID- 10078552
TI  - Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory
      response to glucose in vivo in rats.
AB  - Prolonged exposure of pancreatic islets to free fatty acids (FFAs) inhibits
      glucose-stimulated insulin secretion (GSIS) in vitro. However, FFA inhibition of
      GSIS has not been clearly demonstrated in vivo. We examined the in vivo effect of
      prolonged elevation of plasma FFAs on GSIS using a two-step hyperglycemic clamp
      in rats treated with a 48-h intravenous infusion of either 20% Intralipid plus
      heparin (INT) (5 microl/min plus heparin, 0.1 U/min; n = 8), oleate (OLE) (1.3
      microEq/min; n = 6), saline (SAL) (n = 6), or bovine serum albumin (BSA) (vehicle
      for OLE; n = 5). Because there was no difference in any of the parameters between
      BSA and SAL rats, these groups were combined as control rats (CONT) (n = 11). At
      the end of the 48-h OLE/INT/CONT infusions, after an overnight fast, plasma
      glucose was clamped for 2 h at 13 mmol/l and for another 2 h at 22 mmol/l.
      Preclamp plasma FFAs were elevated twofold (P < 0.01) versus CONT with both INT
      and OLE (NS, INT vs. OLE). Preclamp glucose, insulin, and C-peptide levels were
      higher in INT than in CONT rats (P < 0.05), suggesting insulin resistance, but
      they were not different in OLE and CONT rats. The insulin and C-peptide responses
      to the rise in plasma glucose from basal to 13 mmol/l were lower in OLE (336 +/-
      72 pmol/l and 1.2 +/- 0.1 nmol/l, P < 0.01 and P < 0.05, respectively) than in
      CONT (552 +/- 54 and 1.9 +/- 0.1) rats, but they were not different between CONT
      and INT rats (648 +/- 150 and 2.0 +/- 0.4). The insulin and C-peptide responses
      to the rise in plasma glucose from 13 to 22 mmol/l were lower in both INT (1,188
      +/- 204 pmol/l and 3.0 +/- 0.3 nmol/l, P < 0.01 and P < 0.001) and OLE (432 +/-
      60 and 1.7 +/- 0.2, P < 0.001 vs. CONT or INT) rats than in CONT rats (1,662 +/-
      174 and 5.0 +/- 0.6). In summary, 1) both INT and OLE decreased GSIS in vivo in
      rats, and 2) the impairing effect of INT on GSIS was less than that of OLE, which
      might be due to the different type of fatty acid (mostly polyunsaturated in INT
      versus monounsaturated as OLE) and/or to differential effects of INT and OLE on
      insulin sensitivity. In conclusion, prolonged elevation of plasma FFAs can
      desensitize the insulin secretory response to glucose in vivo, thus inducing a
      beta-cell defect that is similar to that found in type 2 diabetes.

PMID- 10078553
TI  - Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic
      subunit-related protein.
AB  - A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was
      cloned using a subtractive cDNA expression cloning procedure from mouse
      insulinoma tissue. Two alternatively spliced variants that differed by the
      presence or absence of a 118-bp exon (exon IV) were detected in normal balb/c
      mice, diabetic ob/ob mice, and insulinoma tissue. The longer, 1901-bp full-length
      cDNA encoded a 355-amino acid protein (molecular weight 40,684) structurally
      related (50% overall identity) to the liver glucose-6-phosphatase and exhibited
      similar predicted transmembrane topology, conservation of catalytically important
      residues, and the presence of an endoplasmic reticulum retention signal. The
      shorter transcript encoded two possible open reading frames (ORFs), neither of
      which possessed His174, a residue thought to be the phosphoryl acceptor (Pan CJ,
      Lei KJ, Annabi B, Hemrika W, Chou JY: Transmembrane topology of glucose-6
      phosphatase. J Biol Chem 273:6144-6148, 1998). Northern blot and reverse
      transcription-polymerase chain reaction analysis showed that the mRNA was highly
      expressed in pancreatic islets and expressed more in beta-cell lines than in an
      alpha-cell line. It was notably absent in tissues and cell lines of non-islet
      neuroendocrine origin, and no other major tissue source of the mRNA was found.
      During development, it was expressed in parallel with insulin mRNA. The mRNA was
      efficiently translated and glycosylated in an in vitro translation/membrane
      translocation system and readily transcribed into COS 1, HIT, and CHO cells using
      cytomegalovirus or Rous sarcoma virus promoters. Whereas the liver glucose-6
      phosphatase showed activity in these transfection systems, the IGRP failed to
      show glucose phosphotransferase or phosphatase activity with p-nitrophenol
      phosphate, inorganic pyrophosphate, or a range of sugar phosphates hydrolyzed by
      the liver enzyme. While the metabolic function of the enzyme is not resolved, its
      remarkable tissue-specific expression warrants further investigation, as does its
      transcriptional regulation in conditions where glucose responsiveness of the
      pancreatic islet is altered.

PMID- 10078554
TI  - Structure and promoter activity of an islet-specific glucose-6-phosphatase
      catalytic subunit-related gene.
AB  - In liver and kidney, the terminal step in the gluconeogenic pathway is catalyzed
      by glucose-6-phosphatase (G-6-Pase). This enzyme is actually a multicomponent
      system, the catalytic subunit of which was recently cloned. Numerous reports have
      also described the presence of G-6-Pase activity in islets, although the role of
      G-6-Pase in this tissue is unclear. Arden and associates have described the
      cloning of a novel cDNA that encodes an islet-specific G-6-Pase catalytic subunit
      related protein (IGRP) (Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O'Brien
      RM, Hutton JC: Molecular cloning of a pancreatic islet-specific glucose-6
      phosphatase catalytic subunit related protein (IGRP). Diabetes 48:531-542, 1999).
      We screened a mouse BAC library with this cDNA to isolate the IGRP gene, which
      spans approximately 8 kbp of genomic DNA. The exon/intron structure of the IGRP
      gene has been mapped and, as with the gene encoding the liver/kidney G-6-Pase
      catalytic subunit, it is composed of five exons. The sizes of these exons are 254
      (I), 110 (II), 112 (III), 116 (IV), and 1284 (V) bp, similar to those of the G-6
      Pase catalytic subunit gene. Two interspecific backcross DNA mapping panels were
      used to unambiguously localize the IGRP gene (map symbol G6pc-rs) to the proximal
      portion of mouse chromosome 2. The IGRP gene transcription start site was mapped
      by primer extension analysis, and the activity of the IGRP gene promoter was
      analyzed in both the islet-derived HIT cell line and the liver-derived HepG2 cell
      line. The IGRP and G-6-Pase catalytic subunit gene promoters show a reciprocal
      pattern of activity, with the IGRP promoter being approximately 150-fold more
      active than the G-6-Pase promoter in HIT cells.

PMID- 10078555
TI  - Specific gene expression in pancreatic beta-cells: cloning and characterization
      of differentially expressed genes.
AB  - Identification and characterization of genes expressed preferentially in
      pancreatic beta-cells will clarify the mechanisms involved in the specialized
      properties of these cells, as well as providing new markers of the development of
      type 1 diabetes. Despite major efforts, relatively few beta-cell-specific genes
      have been characterized. We applied representational difference analysis to
      identify genes expressed selectively in the pancreatic beta-cell line betaTC1
      compared with the pancreatic alpha-cell line alphaTC1 and isolated 26 clones
      expressed at higher levels in the beta-cells than in the alpha-cells. DNA
      sequencing revealed that 14 corresponded to known genes (that is, present in
      GenBank). Only four of those genes had been shown previously to be expressed at
      higher levels in beta-cells (insulin, islet amyloid polypeptide, neuronatin, and
      protein kinase A regulatory subunit [RIalpha]). The known genes include
      transcription factors (STAT6) and mediators of signal transduction (guanylate
      cyclase). The remaining 12 genes are absent from the GenBank database or are
      present as expressed sequence tag (EST) sequences (4 clones). Some of the genes
      are expressed in a highly specific pattern-expression in betaTC1 and islet cells
      and in relatively few of the non-beta-cell types examined; others are expressed
      in most cell types tested. The identification of these differentially expressed
      genes may aid in attaining a clearer understanding of the mechanisms involved in
      beta-cell function and of the possible immunogens involved in development of type
      1 diabetes.

PMID- 10078556
TI  - Central nervous system effects of intranasally administered insulin during
      euglycemia in men.
AB  - Insulin receptors have been detected in several structures of the brain, yet the
      biological significance of insulin acting on the brain remains rather unclear. In
      humans, direct central nervous effects of insulin are difficult to distinguish
      from alterations in neuronal functions because of insulin-induced decrease in
      blood glucose levels. Since several intranasally administered viruses, peptides,
      and hormones have been shown to penetrate directly from the nose to the brain, we
      tested whether insulin after intranasal administration likewise has access to the
      brain. After a 60-min baseline period, insulin (20 IU H-Insulin 100 Hoechst) or
      vehicle (2.7 mg/ml m-Cresol) was intranasally administered every 15 min to 18
      healthy subjects according to a double-blind within-subject crossover design.
      Auditory-evoked potentials (AEP) indexing cortical sensory processing were
      recorded while the subjects performed a vigilance task (oddball paradigm) during
      the baseline phase and after 60 min of intranasal treatment with insulin or
      placebo. Blood glucose and serum insulin levels were not affected by intranasal
      insulin. Compared with placebo, intranasal administration of insulin reduced
      amplitudes of the N1 (P < 0.005) and P3 (P < 0.02) components of the AEP and
      increased P3 latency (P < 0.05). The reduction in P3 amplitude was most
      pronounced over the frontal recording site (2.42 +/- 1.00 vs. 4.92 +/- 0.79
      microV, P < 0.0005). At this site, after insulin administration, a broad negative
      shift developed in the AEP between 280 and 500 ms poststimulus (area under the
      curve -166.0 +/- 183.8 vs. 270.8 +/- 138.7 microV x ms after placebo, P < 0.01).
      The results suggest that after intranasal administration, insulin directly enters
      the brain and exerts distinct influences on central nervous functions in humans.

PMID- 10078557
TI  - Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.
AB  - Insulin-mediated changes in blood flow are associated with altered blood flow
      distribution and increased capillary recruitment in skeletal muscle. Studies in
      perfused rat hindlimb have shown that muscle metabolism can be regulated by
      vasoactive agents that control blood flow distribution within the hindlimb. In
      the present study, the effects of a vasoconstrictive agent that has no direct
      effect on skeletal muscle metabolism but that alters perfusion distribution in
      rat hindlimb was investigated in vivo to determine its effects on insulin
      mediated vascular action and glucose uptake. We measured the effects of alpha
      methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate,
      femoral blood flow, hindlimb vascular resistance, and glucose uptake in control
      and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats.
      Blood flow distribution within the hindlimb muscles was assessed by measuring the
      metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for
      capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion
      alone increased mean arterial blood pressure by 25% and increased hindlimb
      vascular resistance but caused no change in femoral blood flow. These changes
      were associated with decreased hindlimb 1-MX metabolism indicating less capillary
      flow. Insulin infusion caused decreased hindlimb vascular resistance that was
      associated with increased femoral blood flow and 1-MX metabolism. Treatment with
      alpha-met5HT infusion commenced before insulin infusion prevented the increase in
      femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT
      infusion had no effect on hindlimb glucose uptake but markedly inhibited the
      insulin stimulation of glucose uptake (P < 0.05) and was associated with
      decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant
      correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose
      uptake but not between femoral blood flow and glucose uptake. The results
      indicate that in vivo, certain types of vasoconstriction in muscle such as
      elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary
      flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this
      kind results from stress-induced increase in sympathetic outflow, then this may
      provide a clue as to the link between hypertension and insulin resistance that is
      often observed in humans.

PMID- 10078558
TI  - Resistance to insulin's acute direct hepatic effect in suppressing steady-state
      glucose production in individuals with type 2 diabetes.
AB  - We and others have shown that insulin acutely suppresses glucose production in
      fasting nondiabetic humans and dogs, by both a direct hepatic effect and an
      indirect (extrahepatic) effect, and in diabetic dogs by an indirect effect alone.
      In type 2 diabetes, there is resistance to insulin's ability to suppress hepatic
      glucose production, but it has not previously been determined whether the
      resistance is primarily at the level of the hepatocyte or the peripheral tissues.
      To determine whether the diabetic state reduces the direct effect of insulin in
      humans, we studied nine patients with untreated type 2 diabetes who underwent
      three studies each, 4-6 weeks apart. 1) Portal study (POR): intravenous
      tolbutamide was infused for 3 h with calculation of pancreatic insulin secretion
      from peripheral plasma C-peptide. 2) Peripheral study (PER): equidose insulin was
      infused by peripheral vein. 3) Half-dose peripheral insulin study (1/2 PER):
      matched peripheral insulin levels with study 1. In all studies, glucose was
      clamped at euglycemia, glucose turnover was measured with the constant specific
      activity method, and 3-[3H]glucose was purified by high-performance liquid
      chromatography. Peripheral insulin was lower in POR versus PER but slightly
      higher in POR versus 1/2 PER, although most of the difference could be accounted
      for by higher proinsulin levels in POR (stimulated by tolbutamide). Calculated
      portal insulin was approximately 1.3-fold higher in POR versus PER and
      approximately 2.2-fold higher in POR versus 1/2 PER. In the final 30 min of the
      clamp, glucose production reached a lower steady-state level in PER than in POR
      (4.0 +/- 0.4 vs. 5.3 +/- 0.5 pmol(-1) x kg(-1) x min(-1), P < 0.05), despite the
      higher hepatic insulin level in POR. In contrast with our studies in nondiabetic
      individuals, glucose production was not more suppressed at steady state in POR
      versus 1/2 PER (5.3 +/- 0.4 micromol x kg(-1) x min(-1)), despite much higher
      hepatic insulin levels in POR. In conclusion, this is the first study in patients
      with type 2 diabetes to characterize insulin resistance to the acute direct
      suppressive effect of insulin on hepatic glucose production.

PMID- 10078559
TI  - Effects of fatty acids and ketone bodies on basal insulin secretion in type 2
      diabetes.
AB  - The objective of this study was to assess the role of free fatty acids (FFAs) as
      insulin secretagogues in patients with type 2 diabetes. To this end, basal
      insulin secretion rates (ISR) in response to acute increases in plasma FFAs were
      evaluated in patients with type 2 diabetes and in age- and weight-matched
      nondiabetic control subjects during 1) intravenous infusion of lipid plus heparin
      (L/H), which stimulated intravascular lipolysis, and 2) the FFA rebound, which
      followed lowering of plasma FFAs with nicotinic acid (NA) and was a consequence
      of increased lipolysis from the subject's own adipose tissue. At comparable
      euglycemia, diabetic patients had similar ISR but higher plasma beta
      hydroxybutyrate (beta-OHB) levels during L/H infusion and higher plasma FFA and
      beta-OHB levels during the FFA rebound than nondiabetic control subjects.
      Correlating ISR with plasma FFA plus beta-OHB levels showed that in response to
      the same changes in FFA plus beta-OHB levels, diabetic patients secreted
      approximately 30% less insulin than nondiabetic control subjects. In addition,
      twice as much insulin was secreted during L/H infusion as during the FFA rebound
      in response to the same FFA/beta-OHB stimulation by both diabetic patients and
      control subjects. Glycerol, which was present in the infused lipid (272 mmol/l)
      did not affect ISR. We concluded that 1) assessment of FFA effects on ISR
      requires consideration of effects on ISR by ketone bodies; 2) ISR responses to
      FFA/beta-OHB were defective in patients with type 2 diabetes (partial beta-cell
      lipid blindness), but this defect was compensated by elevated plasma levels of
      FFAs and ketone bodies; and 3) approximately two times more insulin was released
      per unit change in plasma FFA plus beta-OHB during L/H infusion than during the
      FFA rebound after NA. The reason for this remains to be explored.

PMID- 10078560
TI  - Chronic hypoglycemia and diabetes impair counterregulation induced by localized 2
      deoxy-glucose perfusion of the ventromedial hypothalamus in rats.
AB  - Previous studies have demonstrated that the ventromedial hypothalamus (VMH) plays
      a critical role in sensing and responding to systemic hypoglycemia. To evaluate
      the mechanisms of defective counterregulation caused by iatrogenic hypoglycemia
      and diabetes per se, we delivered 2-deoxy-glucose (2-DG) via microdialysis into
      the VMH to produce localized cellular glucopenia in the absence of systemic
      hypoglycemia. Three groups of awake chronically catheterized rats were studied:
      1) nondiabetic (with a mean daily glucose [MDG] of 6.9 mmol/l) BB control rats (n
      = 5); 2) chronically hypoglycemic nondiabetic (3-4 weeks, with an MDG of 2.7
      mmol/l) BB rats (n = 5); and 3) moderately hyperglycemic insulin-treated diabetic
      (with an MDG of 12.4 mmol/l) BB rats (n = 8). In hypoglycemic rats, both glucagon
      and catecholamine responses to VMH glucopenia were markedly (77-93%) suppressed.
      In diabetic rats, VMH 2-DG perfusion was totally ineffective in stimulating
      glucagon release. The epinephrine response, but not the norepinephrine response,
      was also diminished by 38% in the diabetic group. We conclude that impaired
      counterregulation after chronic hypoglycemia may result from alterations of the
      VMH or its efferent pathways. In diabetes, the capacity of VMH glucopenia to
      activate the sympathoadrenal system is only modestly diminished; however, the
      communication between the VMH and the alpha-cell is totally interrupted.

PMID- 10078561
TI  - Brain-derived neurotrophic factor improves blood glucose control and alleviates
      fasting hyperglycemia in C57BLKS-Lepr(db)/lepr(db) mice.
AB  - Systemic administration of brain-derived neurotrophic factor (BDNF) decreases
      nonfasted blood glucose in obese, non-insulin-dependent diabetic C57BLKS
      Lepr(db)/lepr(db) (db/db) mice, with a concomitant decrease in body weight. By
      measuring percent HbA1c in BDNF-treated and pair-fed animals, we show that the
      effects of BDNF on nonfasted blood glucose levels are not caused by decreased
      food intake but reflect a significant improvement in blood glucose control.
      Furthermore, once established, this effect can persist for weeks after cessation
      of BDNF treatment. Oral glucose tolerance tests were performed to examine the
      effects of BDNF on blood glucose control in the fasted state and after an oral
      glucose challenge. BDNF treatment normalized fasting blood glucose from initially
      hyperglycemic levels and also showed evidence for beneficial, although less
      marked, effects on the ability to remove exogenous glucose from blood. One means
      to lower fasting blood glucose is to reduce the glucose output of peripheral
      tissues that normally play a part in the maintenance of fasting hyperglycemia.
      Because the liver is the major endogenous source of glucose in blood during
      fasting, and because hepatic weight and glucose output are increased in type 2
      diabetes, we evaluated the effects of BDNF on liver tissue. BDNF reduced the
      hepatomegaly present in db/db mice, in association with reduced liver glycogen
      and reduced liver enzyme activity in serum, supporting the possible involvement
      of liver tissue in the mechanism of action for BDNF.

PMID- 10078562
TI  - Stretch-induced overproduction of fibronectin in mesangial cells is mediated by
      the activation of mitogen-activated protein kinase.
AB  - An excessive production of extracellular matrix (ECM) proteins in glomerular
      mesangial cells is considered to be responsible for the development of mesangial
      expansion seen in diabetic nephropathy. Mechanical stretch due to glomerular
      hypertension has been proposed as one of the factors leading to an increase in
      the production of ECM proteins in mesangial cells, but the precise mechanism of
      stretch-induced overproduction of ECM proteins has not been elucidated. Herein,
      we provide the evidence that mitogen-activated protein kinase (MAPK) may play a
      key role in the overproduction of fibronectin (FN) in mesangial cells exposed to
      mechanical stretch. MAPK, also termed extracellular signal-regulated kinase (ERK)
      and c-Jun NH2-terminal kinase (JNK), was activated by mechanical stretch in time-
      and intensity-dependent manners. Stretch-induced activation of ERK was inhibited
      by herbimycin A, a tyrosine kinase inhibitor, but not by GF109203X or calphostin
      C, the inhibitors of protein kinase C. Mechanical stretch also enhanced DNA
      binding activity of AP-1, and this enhancement was inhibited by PD98059, an
      inhibitor of MAPK or ERK kinase (MEK). Furthermore, mechanical stretch stimulated
      the expression of FN mRNA followed by a significant increase in its protein
      accumulation. PD98059 could prevent stretch-induced increase in the expression of
      FN mRNA and protein. These results indicate that the activation of ERK may
      mediate the overproduction of ECM proteins in mesangial cells exposed to
      mechanical stretch, an in vitro model for glomerular hypertension seen in
      diabetes.

PMID- 10078563
TI  - Heterogeneous cardiac sympathetic denervation and decreased myocardial nerve
      growth factor in streptozotocin-induced diabetic rats: implications for cardiac
      sympathetic dysinnervation complicating diabetes.
AB  - Heterogeneous myocardial sympathetic denervation complicating diabetes has been
      invoked as a factor contributing to sudden unexplained cardiac death. In subjects
      with diabetic autonomic neuropathy (DAN), distal left ventricular (LV)
      denervation contrasts with preservation of islands of proximal innervation, which
      exhibit impaired vascular responsiveness. The aims of this study were to
      determine whether this heterogeneous pattern of myocardial sympathetic
      denervation occurs in a rat model of diabetes and to explore a potential
      association with regional fluctuations in myocardial nerve growth factor (NGF)
      protein. Myocardial sympathetic denervation was characterized scintigraphically
      using the sympathetic neurotransmitter analog C-11 hydroxyephedrine ([11C]HED)
      and compared with regional changes in myocardial NGF protein abundance and
      norepinephrine content after 6 and 9 months in nondiabetic (ND) and
      streptozotocin-induced diabetic (STZ-D) rats. In ND rats, no difference in
      [11C]HED retention or norepinephrine content was detected in the proximal versus
      distal myocardium. After 6 months, compared with ND rats, myocardial [11C]HED
      retention had declined in the proximal segments of STZ-D rats by only 9% (NS)
      compared with a 33% decrease in the distal myocardium (P < 0.05). Myocardial
      norepinephrine content was similar in both ND and STZ-D rats. At 6 months, LV
      myocardial NGF protein content in STZ-D rats decreased by 52% in the proximal
      myocardial segments (P < 0.01 vs. ND rats) and by 82% distally (P < 0.01 vs. ND
      rats, P < 0.05 vs. proximal segments). By 9 months, [11C]HED retention had
      declined in both the proximal and distal myocardial segments of the STZ-D rats by
      42% (P < 0.01 vs. ND rats), and LV norepinephrine content and NGF protein were
      decreased in parallel. Therefore, 6 months of STZ-induced diabetes results in
      heterogeneous cardiac sympathetic denervation in the rat, with maximal
      denervation occurring distally, and is associated with a proximal-to-distal
      gradient of LV NGF protein depletion. It is tempting to speculate that regional
      fluctuations of NGF protein in the diabetic myocardium contribute to
      heterogeneous cardiac sympathetic denervation complicating diabetes.

PMID- 10078564
TI  - Hemodynamic basis for the acute cardiac effects of troglitazone in isolated
      perfused rat hearts.
AB  - Troglitazone is a thiazolidinedione used for the treatment of NIDDM and
      potentially for other insulin-resistant disease states. Troglitazone has recently
      been shown to increase cardiac output and stroke volume in human subjects. These
      actions are thought to be mediated by the reduction of peripheral resistance, but
      a potential direct effect on cardiac function has not been studied. Therefore, we
      investigated the direct cardiac hemodynamic effects of troglitazone in isolated
      perfused rat hearts. Five groups of hearts were studied. Hearts were tested under
      isovolumetric contraction with a constant coronary flow, and troglitazone (0.2,
      0.5, and 1.0 micromol) was administered by bolus injection. Peak isovolumetric
      left ventricular pressure (LVPmax), peak rate of rise of LVP (dP/dt(max)), and
      peak rate of fall of LVP (dP/dt(min)) were significantly increased 1 min after
      troglitazone administration in a dose-dependent manner, while the heart rate (HR)
      and coronary perfusion pressure (CPP) were significantly decreased (P < 0.05). HR
      was then fixed by pacing and/or CPP was fixed with nitroprusside to eliminate any
      effect of the two variables on the action of troglitazone. With constant HR
      and/or constant CPP, the effect of troglitazone on LVPmax, dP/dt(max), and
      dP/dt(min) was still unchanged. In addition, the positive inotropic, positive
      lusitropic, and negative chronotropic actions of troglitazone were not influenced
      even when hearts were pretreated with prazosin, propranolol, or nifedipine. In
      conclusion, troglitazone has direct positive inotropic, positive lusitropic,
      negative chronotropic, and coronary artery dilating effects. The inotropic and
      chronotropic actions of troglitazone are not mediated via adrenergic receptors or
      calcium channels. These findings have important clinical implications for
      diabetic patients with congestive heart failure.

PMID- 10078565
TI  - Fatty acids modulate the composition of extracellular matrix in cultured human
      arterial smooth muscle cells by altering the expression of genes for proteoglycan
      core proteins.
AB  - In diabetes-associated microangiopathies and atherosclerosis, there are
      alterations of the extracellular matrix (ECM) in the intima of small and large
      arteries. High levels of circulating nonesterified fatty acids (NEFAs) are
      present in insulin resistance and type 2 diabetes. High concentrations of NEFAs
      might alter the basement membrane composition of endothelial cells. In arteries,
      smooth muscle cells (SMCs) are the major producers of proteoglycans and
      glycoproteins in the intima, and this is the site of lipoprotein deposition and
      modification, key events in atherogenesis. We found that exposure of human
      arterial SMCs to 100-300 micromol/albumin-bound linoleic acid lowered their
      proliferation rate and altered cell morphology. SMCs expressed 2-10 times more
      mRNA for the core proteins of the proteoglycans versican, decorin, and syndecan 4
      compared with control cells. There was no change in expression of fibronectin and
      perlecan. The decorin glycosaminoglycan chains increased in size after exposure
      to linoleic acid. The ECM produced by cells grown in the presence of linoleic
      acid bound 125I-labeled LDL more tightly than that of control cells.
      Darglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand,
      neutralized the NEFA-mediated induction of the decorin gene. This suggests that
      some of the NEFA effects are mediated by PPAR-gamma. These actions of NEFAs, if
      present in vivo, could contribute to changes of the matrix of the arterial intima
      associated with micro- and macroangiopathies.

PMID- 10078566
TI  - Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and
      myocardial infarction in type 2 diabetes.
AB  - Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of
      atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic
      gene polymorphism at codon 192 (glutamine/arginine) has been associated with
      coronary artery disease (CAD). To further evaluate the role of this paraoxonase
      gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase
      genotype in 288 type 2 diabetic patients (170 with and 118 without
      angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was
      assessed using polymerase chain reaction followed by AlwI digestion. The
      frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the
      controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age
      adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects
      carrying at least one Arg allele. In the multivariate analysis, this association
      was even stronger after correction for the possible confounders age, sex, smoking
      history, and hypertension. Among current and former smokers, the odds ratio (OR)
      for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P
      < 0.01). The paraoxonase Arg allele was not associated with the history of
      myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD
      (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that
      the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not
      myocardial infarction in type 2 diabetic patients, a risk factor further modified
      by cigarette smoking. This risk could possibly be explained by a reduced ability
      of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.

PMID- 10078567
TI  - Phylogenetic analysis of mitochondrial DNA in type 2 diabetes: maternal history
      and ancient population expansion.
AB  - Several studies have suggested a maternal excess in the transmission of type 2
      (non-insulin-dependent) diabetes. However, the majority of these reports rely on
      patients recalling parental disease status and hence are open to criticism. An
      alternative approach is to study mitochondrial DNA (mtDNA) lineages. The
      hypervariable region 1 of the rapidly evolving noncoding section of mtDNA is
      suitable for investigating maternal ancestry and has been used extensively to
      study the origins of human racial groups. We have sequenced this 347-bp section
      of mtDNA from leukocytes of subjects with type 2 diabetes (n = 63) and age- and
      race-matched nondiabetic control subjects (n = 57). Consensus sequences for the
      two study groups were identical. Pairwise sequence analysis showed unimodal
      distribution of pairwise differences for both groups, suggesting that both
      populations had undergone expansion in ancient times. The distributions were
      significantly different (chi2 = 180, df = 11, P < 0.001); mean pairwise
      differences were 4.7 and 3.8 for the diabetic and control subjects, respectively.
      These data suggest that the diabetic subjects belong to an ancient maternal
      lineage that expanded before the major expansion observed in the nondiabetic
      population. Phylogenetic trees constructed using maximum parsimony, neighbor
      joining, Fitch-Margolish, or maximum likelihood methods failed to show the
      clustering of all (or a subset) of the diabetic subjects into one or more
      distinct lineages.

PMID- 10078568
TI  - Identification and functional analysis of novel human melanocortin-4 receptor
      variants.
AB  - Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in
      mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia.
      These phenotypes resemble common forms of human obesity, which are late-onset and
      frequently accompanied by NIDDM. It is not clear whether sequence variation of
      the MC4-R gene contributes to obesity in humans. Therefore, we examined the human
      MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three
      allelic variants were identified, including two novel ones, Thr112Met and
      Ile137Thr. To analyze possible functional alterations, the variants were cloned
      and expressed in vitro and compared with the wild-type receptor. One of the novel
      variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found
      to be severely impaired in ligand binding and signaling, raising the possibility
      that it may contribute to development of obesity. Furthermore, our results also
      suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a
      common cause of obesity in the population studied, given the low frequency of
      functionally significant mutations.

PMID- 10078569
TI  - Exclusion of insulin receptor substrate 2 (IRS-2) as a major locus for early
      onset autosomal dominant type 2 diabetes.
AB  - We investigated whether variability at the insulin receptor substrate (IRS)-2
      locus plays a role in the etiology of early-onset autosomal dominant type 2
      diabetes. By means of radiation hybrid mapping, we placed the human IRS-2 gene on
      13q at 8.6 cRays from SHGC-37358. Linkage between diabetes and two polymorphic
      markers located in this region (D13S285 and D13S1295) was then evaluated in 29
      families with early-onset autosomal dominant type 2 diabetes. Included were 220
      individuals with diabetes, impaired glucose tolerance, or gestational diabetes
      (mean age at diabetes diagnosis 36 +/- 17 years) and 146 nondiabetic subjects.
      Overall, strongly negative logarithm of odds (LOD) scores for linkage with
      diabetes were obtained by multipoint parametric analysis (LOD score -45.4 at
      D13S285 and -40.9 at D13S1295). No significant evidence of linkage was obtained
      under the hypothesis of heterogeneity or by nonparametric methods. Fourteen
      pedigrees for which linkage could not be excluded (LOD score > -2.0) were
      screened for mutations in the IRS-2 coding region by dideoxy fingerprinting.
      However, no mutations segregating with diabetes could be detected in these
      families. These data indicate that IRS-2 is not a major gene for early-onset
      autosomal dominant type 2 diabetes, although a role of mutations in the promoter
      region cannot be excluded at this time.

PMID- 10078570
TI  - The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed
      in African-Americans.

PMID- 10078571
TI  - Identification of mutations in the hepatocyte nuclear factor-1alpha gene in
      Japanese subjects with early-onset NIDDM and functional analysis of the mutant
      proteins.

PMID- 10078572
TI  - Mice transgenic for an expanded CAG repeat in the Huntington's disease gene
      develop diabetes.
AB  - The autosomal dominant neurological syndrome of Huntington's disease has been
      modeled in transgenic mice by the expression of a portion of the human huntingtin
      gene together with 140 CAG repeats (the R6/2 strain). The mice develop
      progressive chorea with onset at approximately 9 weeks of age and with death at
      approximately 13 weeks. Associated symptoms include weight loss and polyuria in
      the absence of eating or drinking deficits. We have found that these mice have
      insulin-responsive diabetes. Fasting glucose was 211 + 19 mg/dl in R6/2 mice
      compared with 93 + 5 mg/dl in C57/B6 controls (n = 12, both groups; P < 0.01).
      Administration of insulin intraperitoneally led to a reduction in blood glucose.
      At 12.5 weeks, animals were killed and pancreas weighed and analyzed for insulin
      and glucagon. Pancreatic mass in R6/2 mice was the same as controls, and islets
      appeared normal in morphology without lymphocytic infiltration.
      Immunohistochemical staining showed dramatic reductions in glucagon in the alpha
      cells and in insulin in the beta-cells. Direct tissue assays showed glucagon and
      insulin content were reduced to only 10 and 15% of controls, respectively.
      Diabetes has been reported as being more common in Huntington's disease and other
      triplet repeat disorders. The R6/2 mouse should prove useful for elucidating the
      mechanism of diabetes in these genetic diseases.

PMID- 10078573
TI  - Prevention of autoimmune recurrence and rejection by adenovirus-mediated CTLA4Ig
      gene transfer to the pancreatic graft in BB rat.
AB  - Type 1 diabetes is the result of a selective destruction of pancreatic islets by
      autoreactive T-cells. Therefore, in the context of islet or pancreas
      transplantation, newly transplanted beta-cells are threatened by both recurrent
      autoimmune and alloimmune responses in recipients with type 1 diabetes. In the
      present study, using spontaneously diabetic BB rats, we demonstrate that whereas
      isolated islets are susceptible to autoimmune recurrence and rejection,
      pancreaticoduodenal grafts are resistant to these biological processes. This
      resistance is mediated by lymphohematopoietic cells transplanted with the graft,
      since inactivation of these passenger cells by irradiation uniformly rendered the
      pancreaticoduodenal grafts susceptible to recurrent autoimmunity. We further
      studied the impact of local immunomodulation on autoimmune recurrence and
      rejection by ex vivo adenovirus-mediated CTLA4Ig gene transfer to
      pancreaticoduodenal grafts. Syngeneic DR-BB pancreaticoduodenal grafts transduced
      with AdmCTLA4Ig were rescued from recurrent autoimmunity. In fully
      histoincompatible LEW-->BB transplants, in which rejection and recurrence should
      be able to act synergistically, AdmCTLA4Ig transduced LEW-pancreaticoduodenal
      allografts enjoyed markedly prolonged survival in diabetic BB recipients. In situ
      reverse transcription-polymerase chain reaction revealed that transferred CTLA4Ig
      gene was strongly expressed in both endocrine and exocrine tissues on day 3.
      These results indicate the potential utility of local CD28-B7 costimulatory
      blockade for prevention of alloimmune and autoimmune destruction of pancreatic
      grafts in type 1 diabetic hosts.

PMID- 10078574
TI  - Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not
      phosphatidylinositol 3-kinase in rat skeletal muscle.
AB  - Sustained hyperglycemia impairs insulin-stimulated glucose utilization in the
      skeletal muscle of both humans and experimental animals--a phenomenon referred to
      clinically as glucose toxicity. To study how this occurs, a model was developed
      in which hyperglycemia produces insulin resistance in vitro. Rat extensor
      digitorum longus muscles were preincubated for 4 h in Krebs-Henseleit solution
      containing glucose or glucose + insulin at various concentrations, after which
      insulin action was studied. Preincubation with 25 mmol/l glucose + insulin (10
      mU/ml) led to a 70% decrease in the ability of insulin (10 mU/ml) to stimulate
      glucose incorporation into glycogen and a 30% decrease in 2-deoxyglucose (2-DG)
      uptake, compared with muscles incubated with 0 mmol/l glucose. Glucose
      incorporation into lipid and its oxidation to CO2 were marginally diminished, if
      at all. The alterations of glycogen synthesis and 2-DG uptake were first evident
      after 1 h and were maximal after 2 h of preincubation; they were not observed in
      muscles preincubated with 25 mmol/l glucose + insulin for 5 min. Preincubation
      for 4 h with 25 mmol/l glucose in the absence of insulin produced a similar
      although somewhat smaller decrease in insulin-stimulated glycogen synthesis;
      however, it did not alter 2-DG uptake, glucose oxidation to CO2, or incorporation
      into lipids. Studies of insulin signaling in the latter muscles revealed that
      activation of Akt/protein kinase B (PKB) was diminished by 60%, compared with
      that of muscles preincubated in a glucose-free medium; whereas activation of
      phosphatidylinositol (PI) 3-kinase, an upstream regulator of Akt/PKB in the
      insulin-signaling cascade, and of mitogen-activated protein (MAP) kinase, a
      parallel signal, was unaffected. Immunoblots demonstrated that this was not due
      to a change in Akt/PKB abundance. The results indicate that hyperglycemia-induced
      insulin resistance can be studied in rat skeletal muscle in vitro. They suggest
      that impairment of insulin action in these muscles is related to inhibition of
      Akt/PKB by events that do not affect PI 3-kinase.

PMID- 10078575
TI  - Muscle fiber type-specific defects in insulin signal transduction to glucose
      transport in diabetic GK rats.
AB  - To determine whether defects in the insulin signal transduction pathway to
      glucose transport occur in a muscle fiber type-specific manner, post-receptor
      insulin-signaling events were assessed in oxidative (soleus) and glycolytic
      (extensor digitorum longus [EDL]) skeletal muscle from Wistar or diabetic GK
      rats. In soleus muscle from GK rats, maximal insulin-stimulated (120 nmol/l)
      glucose transport was significantly decreased, compared with that of Wistar rats.
      In EDL muscle from GK rats, maximal insulin-stimulated glucose transport was
      normal, while the submaximal response was reduced compared with that of Wistar
      rats. We next treated diabetic GK rats with phlorizin for 4 weeks to determine
      whether restoration of glycemia would lead to improved insulin signal
      transduction. Phlorizin treatment of GK rats resulted in full restoration of
      insulin-stimulated glucose transport in soleus and EDL muscle. In soleus muscle
      from GK rats, submaximal and maximal insulin-stimulated insulin receptor
      substrate (IRS)-1 tyrosine phosphorylation and IRS-1-associated
      phosphatidylinositol (PI) 3-kinase activity were markedly reduced, compared with
      that of Wistar rats, but only submaximal insulin-stimulated PI 3-kinase was
      restored after phlorizin treatment. In EDL muscle, insulin-stimulated IRS-1
      tyrosine phosphorylation and IRS-1-associated PI-3 kinase were not altered
      between GK and Wistar rats. Maximal insulin-stimulated Akt (protein kinase B)
      kinase activity is decreased in soleus muscle from GK rats and restored upon
      normalization of glycemia (Krook et al., Diabetes 46:2100-2114, 1997). Here, we
      show that in EDL muscle from GK rats, maximal insulin-stimulated Akt kinase
      activity is also impaired and restored to Wistar rat levels after phlorizin
      treatment. In conclusion, functional defects in IRS-1 and PI 3-kinase in skeletal
      muscle from diabetic GK rats are fiber-type-specific, with alterations observed
      in oxidative, but not glycolytic, muscle. Furthermore, regardless of muscle fiber
      type, downstream steps to PI 3-kinase (i.e., Akt and glucose transport) are
      sensitive to changes in the level of glycemia.

PMID- 10078576
TI  - Histopathological study of placental bed biopsy in placenta previa.
AB  - BACKGROUND: To study placental bed biopsy changes in placenta previa and normally
      implanted placenta. SUBJECT AND METHOD: Fifty placental bed biopsies from 50
      patients with placenta previa and 50 placental bed biopsies from normally
      implanted placenta were taken at cesarean section. Placental bed biopsy was
      stained with hematoxyline and eosin for histological examination. Both the groups
      were compared for trophoblastic invasion and vascular changes of placental bed
      spiral arteries. Statistical analysis was done by Chi-square test. RESULTS:
      Placenta bed biopsy was representative in 42/50 (84%) biopsy samples of the study
      group (placenta previa) and 35/50 (70%) of the control group (normally located
      placenta). Trophoblastic giant cell migration into decidua was present in 100% of
      representative samples of both the groups while migration into myometrium was
      seen in 66.67% and 51.14% of samples of study and control group. Average number
      of trophoblastic giant cells per sample was significantly higher in placenta
      previa (decidua 41.3%, myometrium 52%) than the control group (decidua 17.4%;
      myometrium 14.5%). Trophoblastic giant cell infiltration into myometrial spiral
      arterioles was higher in placenta previa (81.83 cells per vessel). Percentage of
      myometrial spiral arterioles showing physiological changes was significantly
      higher in the study group (50.39%) compared to the control group (21.14%).
      Incidence of inflammatory cell infiltration was higher in the study group
      (42.86%). Hemorrhage into decidua and myometrium were seen in biopsy samples of
      the placenta previa. CONCLUSION: Placenta previa is associated with significantly
      higher trophoblastic giant cell infiltration and physiological changes of the
      myometrial spiral arterioles.

PMID- 10078577
TI  - Water-gymnastics reduced the intensity of back/low back pain in pregnant women.
AB  - OBJECTIVE: To investigate if water-gymnastics during pregnancy may reduce the
      intensity of back/low back pain and the number of days on sick-leave. METHODS: A
      prospective, randomized study. One hundred and twenty-nine women were randomized
      to participate in water-gymnastics once a week during the second half of
      pregnancy and 129 were randomized to a control group. The women in both groups
      filled in questionnaires in gestational weeks 18, 34 and within the first
      postpartum week. Every day from week 18 to labor they assessed the intensity of
      back/low back pain. RESULTS: Back pain intensity increased during pregnancy. No
      excess risk for the pregnancy associated with water-gymnastics was observed. The
      women participating in water-gymnastics recorded a lower intensity of back/low
      back pain. The total number of days on sick-leave because of back/low back pain
      was 982 in the water-gymnastics group (124 women) compared with 1484 in the
      control group (120 women). After weeks 32 33, seven women in the water-gymnastics
      group compared with 17 in the control group were on sickleave because of back/
      low back pain (p=0.031). CONCLUSIONS: Intensity of back/low back pain increased
      with advancing pregnancy. There was no excess risk for urinary or vaginal
      infections associated with water-gymnastics. Water-gymnastics during the second
      half of pregnancy significantly reduced the intensity of back/ low back pain.
      Water-gymnastics decreased the number of women on sick-leave because of back/low
      back pain. Water-gymnastics during pregnancy can be recommended as a method to
      relieve back pain and may reduce the need for sick-leave.

PMID- 10078578
TI  - Antepartum hemorrhage of unknown origin--what is its clinical significance?
AB  - BACKGROUND: Antepartum hemorrhage of unknown origin is a common antenatal
      complication, accounting for more than half of the cases of antepartum
      hemorrhage. Few investigators had reported the importance of this condition and
      the proper management. METHOD: The present study reviewed retrospectively 718
      cases with singleton pregnancies diagnosed as having antepartum hemorrhage of
      unknown origin after 24 weeks from 1991 to 1996 and compared their pregnancy
      outcomes with controls who delivered during the same period of time as the study
      cases. Clinical and ultrasound examinations were performed in all recruited cases
      to exclude accidental hemorrhage, placenta previa or lower genital tract
      bleeding. RESULTS: Patients with antepartum hemorrhage of unknown origin ran a
      higher risk of spontaneous preterm labor (p<0.001). The birthweight, when
      adjusted for gestation, did not differ between the two groups. Labor induction
      rate and cesarean section rates were significantly higher in the antepartum
      hemorrhage group. The incidences of major antepartum complications and neonatal
      complications did not differ between the two groups. There were more babies with
      congenital abnormalities in the antepartum hemorrhage group (p<0.001) and
      perinatal mortality rate was also higher, though this difference was not
      statistically significant. CONCLUSION: The main fetal risks associated with
      antepartum hemorrhage of unknown origin is preterm labor and its subsequent fetal
      complications. A small but significant proportion of these pregnancies might be
      associated with fetal congenital abnormalities. Routine induction at term for
      this group of patients is of questionable value as adverse fetal outcomes are
      mostly associated with those that delivered prematurely, or with babies with
      congenital malformations. When gross fetal abnormalities could be reasonably
      excluded, labor induction at term should only be contemplated in the presence of
      other obstetric indications.

PMID- 10078579
TI  - Hemostatic variables as independent predictors for fetal growth retardation in
      preeclampsia.
AB  - BACKGROUND: Preeclampsia is a major contributor to perinatal disease and fetal
      growth retardation (FGR). It has been suggested that increased intravascular
      coagulation, fibrin deposition in spiral arteries and hypoperfusion of the
      placenta are involved in these pregnancy complications. METHODS: Multiple
      variables of the hemostatic system and lipid metabolism, as well as clinical
      features, were entered into univariate and multivariate models in order to
      examine the association with preeclampsia and FGR. RESULTS: Two hundred women
      with preeclampsia and 97 normotensive pregnant women were examined. Plasma levels
      of the thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor free
      antigen (TFPI-Fag), protein S free antigen, plasminogen activator inhibitor type
      1 (PAI-1) activity and serum levels of triglycerides were significantly
      increased, whereas plasma levels of antithrombin (AT), fibrinogen, C4b-binding
      protein (C4b-BP), PAI-2 antigen and serum HDL-cholesterol levels were decreased
      in the presence of preeclampsia. In the multivariate regression analysis, high
      TFPI-Fag plasma levels were associated with the presence of preeclampsia. The
      presence of FGR was in the univariate analysis associated with decreased PAI-1
      activity and lower concentrations of fibrin, fibrinogen, factor VII antigen and
      PAI-2 antigen, as well as with evidence of macroscopic placental infarction. In a
      multivariate regression model, low maternal weight, placental infarction and low
      PAI-2 levels were predictors for low birth weight. In a logistic regression
      model, with the presence or absence of FGR as the dependent variable, male sex of
      the infant, placental infarction, low PAI-1 activity and factor VII antigen or
      PAI-2 antigen levels were independent predictors. CONCLUSIONS: Our results are
      consistent with activated coagulation in the placental vessels in preeclampsia. A
      low concentration of PAI-2 antigen in plasma emerged as the most consistent risk
      factor for preeclampsia and FGR.

PMID- 10078580
TI  - Labor induction by vaginal misoprostol in grand multiparous women.
AB  - BACKGROUND: Grand multiparous women in poor and under-privileged settings run a
      high risk of uterine rupture at labor induction. The purpose was to elucidate
      whether vaginal misoprostol medication is a safe and cost-effective alternative
      induction method in grand multiparous women, in whom, under prevailing
      circumstances, induction by oxytocin is associated with high risk of adverse
      maternal outcome of pregnancy. METHOD: One hundred and sixty-five grand
      multiparous parturient women with five or more previous deliveries were divided
      into two groups. The first group (n=134) had the fetus alive and the second
      (n=31) had late intrauterine fetal death. Both groups were subject to induction
      of labor by use of vaginal misoprostol in a dose of 50 microg (live fetus) and
      100 microg (intrauterine fetal death). No additional oxytocin was utilised.
      RESULTS: Labor induction by vaginal misoprostol was successful in grand
      multiparous women. The proportion of women requiring a Cesarean section was 6.0%,
      which is less than one third of the average Cesarean section rate in the setting
      studied. Women with fetus alive had significantly shorter application-to
      expulsion interval (AEI) than women with fetal death (10.1 versus 15.4 hours;
      p=0.039). Significantly shorter AEI was recorded in women with prelabor rupture
      of membranes (9.1 hours) than in women with intact membranes (12.9 hours)
      (p=0.01). With Bishop's score > or = 5 and < 5 AEI was 8.7 hours and 14.4 hours,
      respectively (p=0.001). No significantly adverse neonatal or maternal outcomes of
      pregnancy were registered and it was specifically noted that no uterine rupture
      occurred among the 165 grand multiparous women induced. CONCLUSIONS: Induction of
      under-privileged grand multiparous women with live fetus or with fetal death can
      be performed safely and cost-effectively by vaginal misoprostol.

PMID- 10078581
TI  - Multiple pregnancies with single intrauterine demise. Description of twenty-eight
      pregnancies.
AB  - METHODS: Retrospective study of multiple pregnancies and deliveries with single
      intrauterine demise, in a five years' study period. RESULTS: Of a total of 13,840
      deliveries in the study period, 355 represented multiple pregnancies with two or
      more fetuses from conception: 310 twin pregnancies and 45 triplets or higher.
      Twenty-eight multiple pregnancies were complicated by single intrauterine death:
      in six cases (group A) as first trimester spontaneous fetal loss, in nine cases
      (group B) due to selective fetal reduction, and in thirteen pregnancies as
      spontaneous intrauterine demise occurring in the second or third trimester (group
      C). In group A, no specific cause of death was proven. In group C, four cases of
      death were caused by twin transfusion syndrome, three cases by severe
      intrauterine growth retardation, four cases by placental insufficiency, one case
      by placental abruption striking one of the twins, whereas the last death was
      undefined. In group A, mean gestational age at delivery was 33 completed weeks.
      In group C, five monochorionic pregnancies were delivered at median gestational
      age 30 weeks and seven dichorionic pregnancies at 34 weeks (the chorionicity was
      indefinite in one case). The neonatal complications of the forty-two live born
      babies included prematurity problems only, except for one case of congenital
      anemia in a transfusion syndrome donor twin. None of the mothers showed signs of
      intravascular coagulopathy. CONCLUSION: The main problem for the surviving twin
      was prematurity - not the sibling's death.

PMID- 10078582
TI  - Relation between hemoglobin discordance and adverse outcome in monochorionic
      twins.
AB  - BACKGROUND: The effects of discrepancies in the birth weight and hemoglobin
      concentration ([Hb]) at the birth on infant outcome have not been fully
      investigated in monochorionic (MC) and dichorionic (DC) twins. METHODS: A
      retrospective study of 95 twin pregnancies. All 190 neonates (68 MC twins and 122
      DC twins) were admitted to the neonatal intensive care unit, and the [Hb] was
      determined soon after birth. The [Hb] discordance represents the [Hb] of the
      smaller twin expressed as a percentage of the [Hb] of the larger twin. Infants
      were followed-up until 1 year of corrected age and their psychomotor development
      was evaluated between 12 and 18 months. RESULTS: One DC infant died by 1 year of
      age. Twelve MC infants and eight DC infants had disabilities by 1.5 year of age.
      In the MC group, 11 infants (28%) of 20 pairs with an intertwin [Hb] discordance
      >100 had disabilities compared with one (3.6%) of 14 pairs with an [Hb]
      discordance < or = 100 (p<0.05). A similar trend was observed in the DC group,
      but the difference was not significant. The incidence of disabled infants
      increased as the intertwin birth weight discordance increased in MC twins.
      CONCLUSIONS: An adverse outcome at 1 year of age in MC twins was associated with
      a greater birth weight discordance and an [Hb] disordance that indicated
      polycythemia in the smaller twin.

PMID- 10078583
TI  - A cost comparison of infertility treatment for clomiphene resistant polycystic
      ovary syndrome.
AB  - BACKGROUND: The study compares treatment outcome and costs of ovulation induction
      cycles and in vitro fertilization cycles in infertile women with clomiphene
      resistant polycystic ovary syndrome. METHODS: Twenty-eight infertile women with
      clomiphene resistant polycystic ovary syndrome referred to a university clinic
      were prospectively randomized to ovulation induction or in vitro fertilization.
      Forty-one ovulation induction cycles and thirty in vitro fertilization cycles
      were performed. Mann-Whitney U-test was used for between group comparisons and
      frequencies were compared with Fisher's exact test. RESULTS: More pregnancies per
      completed cycle were noted in the in vitro fertilization group than in the
      ovulation induction group. Drug costs were not much higher in the in vitro
      fertilization group but treatment costs were higher due to the additional costs
      of ovum pick up and embryo transfer. The cost per pregnancy was about twice as
      high in the ovulation induction group as in the in vitro fertilization group. The
      cost per term pregnancy including delivery was 1.6 times higher in the ovulation
      induction group. CONCLUSION: For a group of obese women with clomiphene resistant
      polycystic ovary syndrome, in vitro fertilization seems a cost-effective
      treatment.

PMID- 10078584
TI  - Which women stop smoking? A population-based study of 403 pregnant smokers.
AB  - OBJECTIVE: To describe, in detail, the smoking cessation process during
      pregnancy, and to find out which women are most and least successful at reducing
      or giving up smoking. DESIGN: Prospective, population-based study. SETTING: All
      antenatal clinics in Kronoberg County in southern Sweden. SUBJECTS: Four hundred
      and three women, smoking at the time of conception, and registered for antenatal
      care in the period June 1993 to September 1994. MAIN OUTCOME MEASURES: Self
      reported number of cigarettes smoked per day and percentage of smoking women in
      different weeks of pregnancy. Noted by midwives on special forms. RESULTS: At the
      time of registration at the antenatal clinic, the proportion of smoking women had
      fallen from 100% to 76%, and at the postpartum check-up, the proportion had
      fallen further to 56%. For the women still smoking, the mean number of smoked
      cigarettes per day fell from 14.1 before the pregnancy, to 8.6 in week 12, and
      6.3 in week 40, and then rose to 9.5 after the pregnancy. Heavy smokers and women
      with smoking partners continued smoking to a greater extent, as did multiparae
      and women in unqualified jobs. CONCLUSION: The individual anti-smoking advice
      given during pregnancy should be aimed primarily at these risk groups, and the
      partner should be involved in the woman's attempt to cease smoking. There is much
      left to be done at the antenatal clinic, as more than half of the women were
      still smoking a few months after pregnancy.

PMID- 10078585
TI  - Deaths among women of reproductive age in Cape Verde: causes and avoidability.
AB  - SUBJECT: In 1992-93 all deaths (n=97) of women 15 to 49 years old in three
      islands of Cape Verde were investigated to determine the cause of death, the
      maternal mortality ratio, the reliability of cause-of-death ascertainment, and
      the level of avoidability. METHOD: Data were obtained through interviews with the
      deceased person's family members and other knowledgeable persons (verbal autopsy)
      and through hospital files. RESULTS: The overall mortality rate was 163 per
      100,000 women 1549 years old, and the maternal mortality ratio was 127 per
      100,000 live births. A plausible diagnosis could be determined in 77%. The most
      frequent causes of death were circulatory disorders, external causes, maternal
      causes, infectious diseases. and neoplasms. CONCLUSIONS: It was estimated that
      three of four of the deaths were avoidable with locally available resources.
      Since access to health care in the study area is not a major hindrance, a further
      decrease of female mortality depends mainly on improved quality of care in health
      facilities.

PMID- 10078586
TI  - Eating disorders and gynecology: knowledge and attitudes among clinicians.
AB  - BACKGROUND: Eating disorders are common, responsive to treatment and affect women
      at a peak age of reproductive function, often presenting via gynecological and
      obstetric sequelae. The author wished to examine gynecologists' knowledge and
      attitudes towards them. METHOD: Following a pilot study, a questionnaire
      concerning eating disorders was designed covering aspects of diagnosis,
      characteristic gynecological manifestations, treatment, and attitudes. All
      gynecologists and obstetricians with more than 1 year of experience from four
      teaching hospitals in Australia and the United Kingdom were sent the anonymous,
      confidential postal questionnaire. One hundred and fifteen doctors replied, with
      a response rate of 86%. RESULTS: Only 20% of respondents were confident of
      diagnosing eating disorders. Various diagnostic misconceptions were revealed; for
      example, 42% overestimated weight loss in anorexia nervosa by 20% or more, and
      28% wrongly believed that a sense of strict dietary control' was a feature of
      bulimia nervosa. Clinicians had least knowledge of bulimia nervosa,
      underestimating its treatment response. Surprisingly, the greatest deficits in
      knowledge were of endocrinology and gynecological sequelae. For example, 79%
      underestimated amenorrhea in anorexia nervosa by 25%, and 85% wrongly believed
      that regular menses was characteristic of bulimia nervosa at normal weight.
      Consultants demonstrated significantly more knowledge than junior grades. Thirty
      one percent of respondents held pejorative attitudes to eating disorders, which
      over-represented men (p=0.045) who were also more likely than women to see
      bulimia nervosa as untreatable (p=0.01). CONCLUSION: The author suggests that
      these deficits might be addressed by development of simpler screening
      questionnaires for non-specialists, and elucidation of the interface between
      eating disorders and reproductive physiology.

PMID- 10078587
TI  - Macrophage infiltration and angiogenesis in cervical squamous cell carcinoma-
      clinicopathologic correlation.
AB  - BACKGROUND: The role of angiogenesis and inflammatory cell response in predicting
      disease outcome was evaluated in various malignant tumors. However, the data
      relating to cervical cancer remains equivocal. This study evaluates the
      prognostic significance of microvessel counts and peritumoral macrophage
      infiltrates in squamous cell carcinoma of the uterine cervix. METHODS: Seventy
      five cervical squamous cell carcinomas were stained immunohistochemically by two
      endothelial markers- anti-CD31 and Ulex Europaeus lectin I (UEA-I), and the
      macrophage- specific marker anti-CD68. Microvessel and macrophage counts were
      performed using a grid at X200 and X400 magnification, respectively, in areas of
      maximal density ('hot spots'). Five fields were scanned. Microvessel counts were
      correlated with macrophage density, and both were correlated with patient age,
      tumor stage, histological grade, and survival. RESULTS: Microvessel counts were
      comparable for ulex lectin (mean 6.8+/-4.8/field) and CD31 (8.7+/-5.3/field), and
      results by both markers correlated (p<0.001). Counts by both markers correlated
      with tumor stage, being higher in stages Ib-II compared to stage III-IV tumors
      (p<0.05). No correlation with age, grade, or survival was found. Macrophage
      counts (mean 13.1+/-12.3 cells/field) did not correlate with any of the clinical
      parameters studied or with microvessel counts. CONCLUSIONS: Microvessel counts
      and macrophage density do not correlate with survival in cervical cancer. Neither
      do they appear to be inter-related. The association between elevated microvessel
      counts and localized disease may reflect peak angiogenic stimuli by neoplastic
      cells. We hypothesize that the beneficial role of macrophages in cellular
      immunity may be opposed by the elaboration of growth factors in the vicinity of
      neoplastic cells.

PMID- 10078588
TI  - Urinary stress incontinence. A urodynamic and quantitative electromyographic
      study of the perineal muscles.
AB  - BACKGROUND: Neurophysiological techniques are increasingly used in examination of
      urinary incontinence. The purpose was to measure the activity in the perineal
      muscles in women with urinary stress incontinence and compare with normal
      subjects by using quantitative EMG methods. METHODS: Twenty-four incontinent
      women and seven normal subjects were evaluated urodynamically and with
      quantitative EMG analysis of interference pattern and single fiber measurements.
      The recordings were made in the pubo rectal and the external anal sphincter
      muscle with empty urinary bladder at rest and maximal voluntary contraction as
      well as during cystometry. RESULTS: The incontinent women had a denser
      interference pattern in the anal sphincter at rest but no differences at maximal
      activation compared to the reference group. No differences in interference
      pattern were noted between the two groups in the pubo rectal muscle. Fiber
      density in the external anal sphincter muscle was increased in the patient group
      (2.01 compared to 1.33, p<0.01). The urethral pressures at rest and activation
      were higher in the normal subjects (p<0.05). The normal subjects showed a denser
      interference pattern in the external anal sphincter muscle during cystometry
      (p<0.05). CONCLUSIONS: Quantitative analysis of the interference pattern and
      fiber density in the perineal muscles in incontinent women showed a denser
      interference pattern at rest and increased fiber density. Both observations
      indicate a peripheral nerve lesion. Furthermore, the interference pattern showed
      signs of reduced central activation in the incontinent women during cystometry.

PMID- 10078589
TI  - The role of the frequency-volume chart in the differential diagnostic of female
      urinary incontinence.
AB  - OBJECTIVE: To investigate the differential diagnostic capacity of the frequency
      volume chart in 132 women with urinary incontinence. MATERIAL AND METHOD: For
      each patient, the readings of two 24-h frequency-volume charts were compared to
      the urodynamic diagnosis which was used as the gold standard in 73 genuine stress
      incontinent women, in 23 urge incontinent women, and in 36 women with mixed
      incontinence. RESULTS: The total voided volume, the mean voided volume, the
      largest single voided volume, and the smallest single voided volume were
      statistically differentiating single parameters among the three groups (p<0.05).
      Applying logistic regression to the two well-defined groups of patients, the one
      with urge incontinence and the one with genuine stress incontinence, the
      frequency of micturition during nighttime revealed the best discriminatory power
      for these conditions. CONCLUSION: This study shows that in the frequency-volume
      chart micturition during nighttime discriminates best between urge and stress
      incontinence.

PMID- 10078590
TI  - Efficacy of methotrexate in the treatment of nonruptured ectopic pregnancy. A six
      year experience at Polish Mother's Memorial Institute.

PMID- 10078591
TI  - The effect of transdermal estrogen replacement therapy on hyperandrogenicity and
      glucose homeostasis in postmenopausal women with NIDDM.

PMID- 10078592
TI  - Route of delivery in triplet pregnancies--an unresolved issue.

PMID- 10078593
TI  - Expression of the E2 envelope glycoprotein of bovine viral diarrhoea virus (BVDV)
      elicits virus-type specific neutralising antibodies.
AB  - A region of genome from the NADL strain of BVDV corresponding to the coding
      sequence for the E2 glycoprotein has been molecularly cloned using RT-PCR. The
      viral cDNA sequence was used to construct vaccinia virus recombinants that
      expressed either the entire E2 coding sequence or fragments of it. These
      recombinants were used to immunise mice of three H-2 haplotypes to investigate
      their ability to elicit a neutralising antibody response against BVDV. Sera from
      mice immunised with the recombinant expressing full length E2 contained high
      levels of virus neutralising antibodies that in addition to giving neutralisation
      of the homologous NADL strain were also able to neutralise the Oregon C24V
      reference strain. These sera failed to give any neutralisation of the Osloss
      reference strain providing evidence for the division of BVDV isolates into at
      least two distinct E2 serotypes. These results were confirmed in gnotobiotic
      lambs. Expression of E2 fragments revealed the presence of at least two distinct
      neutralising epitopes, one of which was localised within the carboxy terminal 90
      amino acids of the protein.

PMID- 10078594
TI  - Strains of bovine herpesvirus 1 that do not express an epitope on glycoprotein E
      in cell culture still induce antibodies that can be detected in a gE-blocking
      ELISA.
AB  - Two bovine herpesvirus 1 (BHV1) field strains that do not express an epitope on
      glycoprotein E (gE) in cell culture were inoculated into calves to examine
      whether their sera became positive in a gE-blocking ELISA that detects antibodies
      against gE. This gE-blocking ELISA uses one monoclonal antibody that is directed
      against the above mentioned epitope. All calves, except one, infected with these
      gE-epitope negative BHV1 strains, became positive in this gE-blocking ELISA,
      about two weeks later than in another gE-ELISA and a gB-ELISA. However, cattle
      infected with BHVI strains that do express this particular gE-epitope showed a
      similar type of antibody responses. These findings demonstrate that BHV1 strains
      that do not express a particular gE-epitope in cell culture, still can induce
      antibodies that are detected in a blocking ELISA that measures antibodies against
      that epitope.

PMID- 10078595
TI  - The isolation and enumeration of three feline oral Porphyromonas species from
      subcutaneous abscesses in cats.
AB  - Samples were examined from 15 subcutaneous fight wound abscesses from 15 cats.
      All abscesses were closed at the time of sampling and cats had received no prior
      treatment. Samples were processed within 20 min and quantitative assessment made
      of total facultative and obligately anaerobic flora isolated. Digoxigenin
      labelled whole chromosomal DNA probes directed against three feline members of
      the genus Porphyromonas (P. gingivalis VPB 3492, P. circumdentaria NCTC 12469T
      and P. salivosa VPB 3313) were used to identify members of this genus and
      quantification of these species was made from each cat using colony lifts and
      southern hybridisation from nitrocellulose membranes taken from replicate plates
      from each abscess sample. Twelve of the 15 abscesses yielded a variety of
      facultative and obligately anaerobic (FOA) bacterial species and members of the
      genus Porphyromounas were enumerated from each of these 12 abscesses. Of the 12
      abscesses in which Porphyromonas species were detected, seven contained one
      species only (five contained only P. gingivalis and two contained only P.
      salivosa) three abscesses contained two species (both P. gingivalis and P.
      circumdentaria) and two abscesses contained all three species of Porphyromonas.
      These results show that members of the genus Porphyromonas are likely to be
      significant contributors to the purulent disease process in subcutaneous
      abscesses in cats.

PMID- 10078596
TI  - Virulence-associated factors of uropathogenic Escherichia coli strains isolated
      from pigs.
AB  - Thirty one Escherichia coli strains isolated from pigs with urinary tract
      infections were investigated for presence of virulence factors and plasmid DNA
      profile. The most frequent virulence factors presented by these strains were
      mannose-resistant fimbriae, including P. fimbriae (54.8%) and aerobactin
      production (45.2%). The pap) operon, detected by PCR, was found in 54.8% of the
      strains, which is similar to its frequency in human strains. Other
      characteristics such as the presence of mannose-sensitive hemagglutinin (16.1%),
      indicative of type 1 pili, and production of hemolysin (25.8%), colicin (38.7%)
      and toxins (22.6% for LT and for VT) were less frequent. No strains were positive
      for STa production. Plasmid profiles were variable among isolates from either the
      same or different farms.

PMID- 10078597
TI  - Enhancement of phagocytosis and bacterial killing by heterophils from neonatal
      chicks after administration of Salmonella enteritidis-immune lymphokines.
AB  - During the first week post-hatch, chickens demonstrate an increased
      susceptibility to infection by bacteria such as Salmonella. The purpose of the
      present study was to evaluate the effects of immune lymphokines on phagocytosis
      and killing activities of heterophils in chicks during the first 1-7 days of
      life. Lymphokines isolated from chicken splenic T-cells harvested from Salmonella
      enteriditis (SE)-hyperimmunized hens (SE-ILK), have in past experiments,
      demonstrated augmentation of heterophil activity in day-of-hatch chicks resulting
      in protection from SE organ invasion. The present experiments reveal significant
      increases (p<0.05) in heterophil phagocytosis and killing when comparing chicks
      treated with SE-ILK to control groups in vitro. In SE-ILK-treated groups, a two
      fold or greater increase is noted in heterophil phagocytosis within I h of
      incubation as compared to controls. Heterophils isolated from 1-day-old and 4-day
      old chicks treated with SE-ILK killed significantly greater numbers (p<0.05) of
      SE than heterophils isolated from control groups. By Day 7 post-hatch,
      significance is not noted in the killing activity of heterophils from treated
      groups when compared to control groups. However, heterophils from SE-ILK groups
      continue to kill greater numbers of SE than control groups. These data support SE
      ILK augmentation results in an enhanced heterophil function in chicks during the
      greatest period of susceptibility to Salmonella invasion.

PMID- 10078598
TI  - Rapid detection of Mycobacterium bovis on its lipid profile by thin layer
      chromatography.
AB  - Sixteen Mycobacterium bovis (M. bovis) strains isolated from bovine tissues and
      one standard reference strain of M. bovis AN5 alongwith other species of
      mycobacteria for comparison were investigated for the presence of phenolic
      glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) for rapid identification
      of M. bovis by thin-layer chromatography (TLC). The study indicated presence of
      PGL with an Rf value of 0.75 in chloroform-methanol solvent in all 17 M. bovis
      strains. The dimycocerostate A corresponding to spot A was the major constituent
      among all the three spots in M. bovis strains. TLC appeared to be a promising
      alternative to conventional biochemical methods for identification of M. bovis
      taking into consideration both PGL and PDIM lipids.

PMID- 10078599
TI  - Pasteurella haemolytica leukotoxin induced apoptosis of bovine lymphocytes
      involves DNA fragmentation.
AB  - It has been reported that Pasteurella haemolytica leukotoxin (LKT) induces
      morphologic changes in bovine leukocytes consistent with apoptosis in vitro, but
      DNA fragmentation was not observed. We investigated whether bovine lymphocytes
      undergo DNA fragmentation during LKT-induced apoptosis. Bovine peripheral blood
      lymphocytes were isolated by density gradient centrifugation and exposed to LKT
      or inactive pro-LKT protein from a lktC- mutant strain. After exposure, DNA
      fragmentation in lymphocytes was quantified colorimetrically by diphenylamine
      assay and visualized by agarose gel electrophoresis. At high LKT concentrations,
      bovine lymphocytes were lysed, but at low concentrations, LKT caused DNA
      fragmentation characteristic of apoptosis. Maximal DNA fragmentation in bovine
      lymphocytes was induced by 0.1 TU ml(-1) LKT following 3 h exposure, but only
      background level of DNA fragmentation was observed with the inactive pro-LKT.
      Equine lymphocytes that are resistant to LKT intoxication did not show DNA
      fragmentation following exposure to LKT. Preincubation of LKT with a neutralizing
      anti-LKT monoclonal antibody inhibited LKT-induced DNA fragmentation.
      Electrophoresis of DNA from bovine lymphocytes treated with 0.1 TU ml(-1) LKT
      demonstrated the typical 'ladder' pattern of internucleosomal DNA cleavage, the
      hallmark of apoptosis associated with activation of endonucleases. LKT-induced
      DNA fragmentation was inhibited by 0.5 mM ZnCl2, an endonuclease inhibitor. The
      results indicated that LKT at low concentrations induced apoptotic cell death of
      bovine lymphocytes, which may play a role in initiation and persistence of P.
      haemolytica infection.

PMID- 10078600
TI  - Production of malignant catarrhal fever virus-free sheep.
AB  - The study was designed to better define the variables affecting the success of
      the establishment of ovine herpesvirus 2 (OHV-2)-free sheep flocks. A total of 38
      lambs born to OHV-2-positive ewes was selected and divided into four groups.
      Three groups of 10 lambs each were separated from the positive ewes at 2, 2.5 and
      3 months of age, respectively, and maintained in isolation facilities. One group
      of eight remained in the positive flock as controls. Peripheral blood samples
      from each lamb were examined regularly by PCR for OHV-2 DNA. All lambs (100%)
      that were weaned and maintained in isolation from the ages of 2, 2.5 and 3 months
      remained negative until the termination of the experiment at 1 year of age. One
      lamb was discovered to be PCR-positive on the day of isolation at 2.5 months of
      age, and was promptly removed from the isolation group. In contrast, all lambs
      (100%) that remained with the flock became PCR-positive by 6 months of age. The
      data confirmed that, with rare exceptions, separation of lambs from OHV-2
      infected animals at around 2 months of age reliably yields OHV-2-free sheep.
      Appropriate PCR monitoring will enable the rare exceptions to be removed from the
      group, and is recommended as a safety measure.

PMID- 10078601
TI  - Immunogenicity of viral B-cell epitopes inserted into two surface loops of the
      Escherichia coli K12 LamB protein and expressed in an attenuated aroA strain of
      Salmonella typhimurium.
AB  - We previously developed a general procedure which allows the genetic coupling of
      a chosen foreign linear epitope in different 'permissive' sites of a carrier
      protein. By using the outer membrane protein LamB of Escherichia coli K12 as a
      carrier, we were able to express a number of different foreign epitopes at the
      bacterial surface. In the present work, taking advantage of the recent
      determination of the crystal structure of LamB, we inserted two model B-cell
      epitopes i.e.--the C3 epitope from poliovirus (residues 93 to 103 of VP1) and the
      preS2 epitope from hepatitis B virus, (residues 132 to 145)--at the tip of the
      most distal and largest surface exposed region of LamB (after residues 386, into
      loop L9). We also used two previously constructed LamB hybrids, corresponding to
      the insertion of the C3B or preSB epitope into permissive site 153 (lying in the
      middle of the fourth surface loop of LamB), to construct two LamB proteins
      corresponding to the simultaneous insertion of the two different epitopes (with
      one epitope per site). The LamB hybrids were placed under the control of the
      anaerobically inducible pnirB promoter and expressed in a LamB-negative
      derivative of the aroA attenuated strain of S. typhimurium, SL3261. In vitro, the
      recombinant proteins were expressed at a high level (up to 10% of whole cell
      proteins) and in vivo the recombinant plasmids were stably maintained. For both
      epitopes, genetic coupling at site 386 appeared to be more favorable for the
      induction of anti-epitope antibodies than coupling at site 153. Moreover, the
      LamB hybrid corresponding to the simultaneous insertion of the preSB epitope at
      site 153 and of the C3B epitope at site 386 allowed the induction of both anti
      poliovirus and anti-hepatitis B antibodies.

PMID- 10078602
TI  - Induction of a protective immunity against Schistosoma mansoni with ovalbumin
      coupled Sm37-5 coadsorbed with granulocyte-macrophage colony stimulating factor
      (GM-CSF) or IL-12 on alum.
AB  - A previous study has shown that Sm37-5 is a major B cell epitope of Sm37-GAPDH.
      This epitope is highly antigenic in human infections and IgG antibody reactivity
      toward this determinant is associated with adolescent resistance to reinfection.
      This led us to test a synthetic peptide corresponding to Sm37-5, coupled to
      ovalbumin, as an anti-schistosome vaccine. Although mice injected with Sm37-5-OVA
      in Freund's adjuvant showed significant protection, immunization in aluminium
      hydroxide failed to induce protection. The adjuvant effect of cytokines (GM-CSF
      or IL-12) associated with the antigen on alum was investigated. With each of
      these two cytokines, significant reductions in the worm burden were obtained (32
      38% with GM-CSF and 27% with IL-12, respectively). In addition, a reduction of
      the egg number trapped in the liver of immunized mice was also observed. Thus,
      protections were obtained with formulations that could potentially be used in
      humans.

PMID- 10078603
TI  - CpG motifs as immune adjuvants.
AB  - Bacterial DNA contains immunostimulatory motifs that trigger an innate immune
      response characterized by the production of predominantly Th1-type cytokines.
      These motifs consist of an unmethylated CpG dinucleotide flanked by two 5'
      purines and two 3' pyrimidines. We examined whether synthetic
      oligodeoxynucleotides (oligos) expressing these motifs would act as adjuvants to
      boost the immune response to DNA- and protein-based immunogens. In vivo
      experiments demonstrate that CpG-containing oligos augment antigen-specific serum
      antibody levels by up to tenfold, and IFNgamma production by up to sixfold. These
      effects were optimized by physically linking the CpG-containing motifs to the
      immunogen.

PMID- 10078604
TI  - Hepatitis A vaccine in healthy adults: a comparison of immunogenicity and
      reactogenicity between two- and three-dose regimens.
AB  - Inactivated hepatitis A virus (HAV) vaccine was administered to 55 healthy
      seronegative adult volunteers to evaluate the immunogenicity and adverse
      reactions of two doses of HAV vaccination (25 units) in comparison with a three
      dose regimen. The volunteers were randomly assigned to receive one of the two
      regimens: 26 were vaccinated with two doses at 0 and 24 weeks (Group 1), and 29
      were vaccinated with three doses at 0, 2, and 24 weeks (Group 2). The vaccine was
      well tolerated and there was no serious adverse reaction. In both groups, the
      seroconversion rate was 100% at week 28. At week 52, all remained positive for
      anti-HAV regardless of a two- or three-dose regimen. No statistically significant
      difference in seroconversion rates and geometric mean titers could be
      demonstrated between the two groups. Thus, the two-dose regimen may be favorable
      to save cost and time for active immunization against hepatitis A.

PMID- 10078605
TI  - Induction of specific cell-mediated immunity in mice by oral immunization with
      Salmonella expressing Onchocerca volvulus glutathione S-transferase.
AB  - Cellular and humoral immune responses of mice to Onchocerca volvulus glutathione
      S-transferase (OvGST) presented via in vivo expression in attenuated Salmonella
      typhimurium were examined and compared with the same antigen administered by
      subcutaneous injection with Freund's adjuvant. After infection with recombinant
      S. typhimurium, maximal numbers of bacteria were recovered from the mesenteric
      lymph nodes and spleens during the second week postinfection. By weeks 3-4,
      bacteria were absent from these tissues. Splenocytes from mice infected with S.
      typhimurium expressing OvGST showed significant and specific proliferative
      responses to OvGST, whereas the non-recombinant S. typhimurium controls and those
      which received the antigen by subcutaneous injection with Freund's adjuvant did
      not. Mice infected with recombinant S. typhimurium had elevated IFN-gamma levels
      over non-recombinant S. typhimurium and placebo controls. but IL-4 and IL-5
      levels were low and did not differ significantly between these groups. Antibody
      responses to OvGST antigen expressed by a recombinant Salmonella vaccine or
      delivered in a purified form with Freund's adjuvant were moderate to high. These
      data suggest that Salmonella can be used as a vaccine delivery vector that
      induces specific cellular and humoral immune responses to Onchocerca volvulus
      antigens. This is the first report to describe the successful application of a
      filarial antigen in a live-vector delivery system as well as the first
      recombinant based filarial vaccine to elicit a cellular immune response similar
      to that described for putative immune endemics.

PMID- 10078606
TI  - Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the
      treatment of genital warts.
AB  - A phase I double-blind, randomized, placebo-controlled study was carried out in
      healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant
      HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two
      healthy male volunteers were randomised to receive three intramuscular injections
      of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel.
      Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule)
      and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse
      events throughout. Immunogenicity was assessed by measuring L2E7 specific in
      vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum
      antibodies. Dose-dependent and long-lived T and B cell immune responses were
      elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both
      safe, well-tolerated and immunogenic. The results allow the selection of the 300
      microg vaccine formulation and accelerated vaccination schedule for phase II
      trials in patients with genital warts.

PMID- 10078607
TI  - Induction of human cytomegalovirus (HCMV)-glycoprotein B (gB)-specific
      neutralizing antibody and phosphoprotein 65 (pp65)-specific cytotoxic T
      lymphocyte responses by naked DNA immunization.
AB  - Plasmids expressing the human cytomegalovirus (HCMV) glycoprotein B (gB) (UL55)
      or phosphoprotein 65 (pp65) (UL83) were constructed and evaluated for their
      ability to induce immune responses in mice. The full-length gB as well as a
      truncated form expressing amino acids 1-680 of gB, and lacking the fragment
      encoding amino acids 681 907 including the transmembrane domain of gB (gB680)
      were evaluated. Immunization of mice with plasmids coding for gB or gB680 induced
      ELISA and neutralizing antibodies, with the highest titres in mice immunized with
      the gB680 plasmid. Mice immunized with the gB plasmid predominantly produced
      IgG2a gB-specific antibody, while the gB680 plasmid raised mostly IgG1 anti-gB
      antibody. Mice immunized with the pp65 plasmid developed pp65-specific cytotoxic
      T lymphocytes (CTL) and ELISA antibodies. Immunization with a mixture of both gB
      and pp65 plasmids raised antibodies to both proteins and pp65-specific CTL,
      indicating a lack of interference between these two plasmids. These results
      suggest that DNA immunization is a useful approach for vaccination against HCMV
      disease.

PMID- 10078608
TI  - Lymphocyte response to tetanus toxin T-cell epitopes: effects of tetanus
      vaccination and concurrent malaria prophylaxis.
AB  - Synthesized T-cell epitopes of tetanus toxin are universally immunogenic and
      serve to enhance immune response when they are used as vaccine carriers of B-cell
      epitopes. The immunogenicity of the P2, P30, and P2P30 T-cell epitopes of tetanus
      toxin and whole tetanus toxoid (TT) was evaluated by in vitro proliferation assay
      of lymphocytes from men with no history of tetanus vaccination who were enrolled
      in a malaria prophylaxis trial. The enhancement of immune response by tetanus
      vaccination (Td) and possible antagonism by the antimalarial drugs, was measured
      by pre- and post-Td comparisons within and between immunized prophylaxis groups
      (primaquine, chloroquine, placebo) and a nonimmunized control group. Constructs
      demonstrated low immunogenicity relative to TT in all groups. Relative to both
      control and its own baseline, the immunized primaquine prophylaxis group was
      distinct in demonstrating significantly increased proliferation against all three
      subunits and at both high (30 microg ml(-1)) and low (3 microg ml(-1))
      concentrations. Immunization elicited significantly increased proliferation
      responses by placebo and chloroquine prophylaxis groups against only the P2P30
      construct. Despite these significant post-Td changes, a low concentration of TT
      0.1 microg ml(-1)) stimulated proliferation 7-10 times over that induced by the
      greatest concentration of the constructs.

PMID- 10078609
TI  - Booster immunization of HIV-1 negative volunteers with HGP-30 vaccine induces
      protection against HIV-1 virus challenge in SCID mice.
AB  - Eleven HIV-1 seronegative subjects previously injected with an HIV-1 p17
      synthetic peptide vaccine (HGP-30) were given two booster immunizations to
      evaluate memory cell responses and the ability to boost cellular and humoral
      immune responses. Five of 11 subjects showed a significant increase in their
      antibody titres to HGP-30 or p17 and 6/11 had T-cell proliferation responses to
      either HGP-30 or p17. HIV-1 virus challenge studies in SCID mice demonstrated
      that 39 of 50 mice (78%) receiving PBMC from 5 of the HGP-30 immunized subjects
      were protected from infection with a different strain of HIV-1 compared to 4 of
      30 mice (13%) that received PBMC from 3 non-immunized subjects (p < 0.001). These
      studies show that booster immunizations with HGP-30 vaccine are safe and non
      toxic and induce protective cell mediated immune responses.

PMID- 10078610
TI  - Oral immunization with a Streptococcal pneumoniae polysaccharide conjugate
      vaccine in enterocoated microparticles induces serum antibodies against type
      specific polysaccharides.
AB  - The authors examined the antibody responses of mice orally immunized with
      pneumococcal polysaccharide (type 23F) or a pneumococcal polysaccharide
      conjugated to the outer membrane protein complex of Neisseria meningitides (23F
      OMPC). These antigens were administered either in solution or entrapped within
      microcapsules. Only the mice receiving the encapsulated conjugate vaccine
      produced significant levels of anti-polysaccharide serum antibodies. These
      responses, observed after a second oral immunization with the conjugate, were
      predominantly IgG. Thus, the conversion from a T-cell-independent to a T-cell
      dependent response, achieved through conjugation was maintained following oral
      delivery. However, no local secretory IgA anti-polysaccharide response was
      detected in these mice indicating that while the OMPC carrier augments orally
      induced IgG responses, it was insufficient for the induction of secretory IgA.

PMID- 10078611
TI  - Immune response to influenza vaccination in a large healthy elderly population.
AB  - Elderly individuals not only demonstrate a greater risk of morbidity and
      mortality from influenza than the young, but also have greater difficulty
      mounting a protective response to influenza vaccine. The mechanism of the
      decreased efficacy of influenza vaccination in the elderly is not well
      understood. The present study was designed to assess the interaction between cell
      mediated and humoral immune responses to influenza vaccine in a large population
      (n = 233) of healthy elderly individuals (mean age = 80.7) living in six
      continuing care retirement communities (CCRCs). While influenza vaccination
      resulted in significant increases in the mean anti-influenza antibody titres and
      mean proliferative responses of peripheral blood mononuclear cells to purified
      subvirion trivalent influenza vaccine one month after vaccination, only 48.9% and
      30.0% of subjects had intact humoral and cell-mediated immune responses,
      respectively. No association was observed between intact cell-mediated and
      humoral responses: 14.7% of subjects had an intact cell-mediated, but not humoral
      response, and 32.6% of subjects had an intact humoral, but not cell-mediated
      response. However, IFNgamma production was significantly correlated with both
      antibody and cell-mediated responses to influenza vaccination, a finding not
      previously reported in the elderly. These results indicate that there is
      considerable heterogeneity among immune responses of the elderly to influenza
      vaccination. This heterogeneity needs to be a major consideration in evaluation
      of new vaccine preparations.

PMID- 10078612
TI  - A model to study the effects of a viral inactivator (beta-propiolactone) on DNA
      ligation and gene expression in E. coli and Cos cells.
AB  - An experimental model to study the effects of viral inactivators on the
      biological properties of DNA was developed. Beta-propiolactone (betaPL) was used
      in this model and its effects on ligation, transfer and gene expression of naked
      DNA were assessed. Evidence that betaPL impairs these two major DNA functions are
      presented. The amounts of betaPL that alter or abolish gene expression and
      prevent DNA cohesive ends ligation were determined. Based on these observations,
      it was concluded that this experimental approach could be used to study the
      effects on the biological properties of DNA of other inactivators used in vaccine
      preparations.

PMID- 10078613
TI  - Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental
      nucleus: a short theoretical review.
AB  - In this review, it is argued that the consequence of bilateral damage to the
      pedunculopontine tegmental nucleus (PPTg) in experimental animals is the
      production of a form of frontal syndrome. Frontal syndrome is a term used to
      describe the behavioural consequences of damage to the frontal lobes in human
      patients. These behavioural changes can be classified as disinhibition of
      behaviour (a release of behavioural control), the production of inappropriate
      behaviour (which in patients can be either inappropriate actions or verbal
      behaviour), and the production of perseverative behaviour (the maintenance of an
      action beyond the point at which it should have been terminated). The
      psychological changes which underlie these behavioural changes are thought to
      involve executive functions, which include such things as the prospective
      planning of sequences of actions, attentional shifting and working memory. In
      this review, I attempt to demonstrate two things: first, that there are
      significant anatomical connections from frontostriatal systems to the PPTg. The
      motor cortex projects directly to the PPTg while the prefrontal cortex contacts
      it via striatal circuitry, forming clear routes by which the frontal lobes can
      communicate with the PPTg. Second, having established the existence of
      connections between frontostriatal systems and the PPTg, behavioural data are
      described. Experimental animals bearing bilateral lesions of the PPTg have been
      examined in a wide variety of tasks. Animals bearing such lesions are not
      impaired in basic processes of feeding, drinking, locomotion, or grooming and
      simple observation of lesioned rats' normal behaviour reveals no obvious gross
      impairment in function. However, the results of more subtle tests reveal a wide
      variety of deficits in various tasks. The outcome of these experiments are in
      many ways contradictory, but in the vast majority of cases, the changes can be
      described as involving disinhibition of behaviour, the release of inappropriate
      behaviour, and the production of perseverative behaviour. Anatomical and
      behavioural data support the conclusion that there are functional connections
      between frontal systems and the PPTg. This review also discusses what
      psychological processes might be served by such connections.

PMID- 10078614
TI  - Glutamate/aspartate and leu-enkephalin immunoreactivity in mammillothalamic
      projection neurons of the rat.
AB  - We have used retrograde transport and immunohistochemistry to study glutamate,
      aspartate, and enkephalin-like immunoreactive pathways from the mammillary nuclei
      to the anterior nuclei of the thalamus. Injections of wheat germ agglutinin
      conjugated to horseradish peroxidase into the anterodorsal thalamic nucleus
      resulted in retrogradely labelled cell bodies in the lateral mammillary nucleus,
      bilaterally, whereas injections into the anteroventral thalamic nucleus resulted
      in retrogradely labelled neurons in the ipsilateral medial mammillary nucleus. In
      three parallel series of sections immunoreacted for glutamate, aspartate, and
      enkephalin, respectively, 50-60% of the retrogradely labelled cell bodies were
      also immunolabelled for glutamate, 50-60% for aspartate, and 40-50% for
      enkephalin. The enkephalin-immunoreactive neurons may coincide with or constitute
      a separate population from the glutamate/aspartate-containing neurons. These
      results are compatible with the possibility that mammillothalamic projection
      neurons may use glutamate and/or aspartate and enkephalin as neurotransmitters.

PMID- 10078615
TI  - Resistance of gonadotropin-releasing hormone neurons to glutamatergic
      neurotoxicity.
AB  - Although many studies provide evidence that glutamatergic pathways regulate the
      secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, it is
      controversial as to whether they act directly upon GnRH neurons. The aim of the
      current study was to determine whether GnRH neurons are susceptible to the
      neurotoxic actions of specific glutamate agonists (N-methyl-D-aspartate [NMDA]
      and kainic acid), the rationale being that neurotoxic loss of GnRH neurons would
      provide evidence that the perikarya possess specific classes of glutamate
      receptor. Unilateral 1-microl injections of NMDA (12-120 mM), kainic acid (0.5
      2.5 mM), or vehicle were stereotaxically directed at the preoptic area
      (mPOA)/diagonal band of Broca (dbB) in the region of the organum vasculosum of
      the lamina terminalis (OVLT) of male adult hamsters (Phodopus sungorus). The
      number and appearance of GnRH neurons were determined by immunocytochemistry 3-8
      days later. The morphology of GnRH neurons in the vicinity of the injection sites
      appeared normal after both kainic acid and NMDA treatment, and there was no
      significant decrease in the numbers of GnRH perikarya identified following these
      treatments. Both agonists caused massive cellular loss when injected directly
      into cortical areas and striatum. In the experimental studies, there was little
      neuronal loss within the mPOA or dbB after either toxin, despite clear neuronal
      loss in areas adjacent to the injection sites, including ventral striatum and
      olfactory cortex. In follow-up studies, immunocytochemical and in situ
      hybridisation analysis of the NMDAR1 and NMDAR2 glutamate receptor subunits
      confirmed their widespread distribution in regions containing GnRH perikarya, but
      no colocalization within GnRH neurons was observed. The susceptibility of neural
      areas to NMDA neurotoxicity did not correlate with any difference in the regional
      expression of these glutamate receptor subunits. The resistance of GnRH neurons
      to the neurotoxic actions of two different glutamate agonists and the failure to
      detect colocalisation of NMDAR1 or NMDAR2 subunits within GnRH perikarya are
      consistent with the notion that the effects of glutamate upon GnRH secretion are
      not exerted directly upon GnRH cell bodies.

PMID- 10078616
TI  - Striatal grafts alleviate deficits in response execution in a lateralised
      reaction time task.
AB  - It has been reported that homotopic neural transplants can ameliorate behavioural
      impairments induced by striatal lesions in a reaction time (RT) task. In the
      present study we seek to replicate and extend this observation in a new
      lateralised choice RT task based on the conventional Skinner box apparatus. Rats
      were trained to make rapid lateralised lever press responses to a visual stimulus
      presented on either the left or the right side of the animal. The RTs required to
      initiate and execute correct responses were recorded, along with other accuracy
      and performance indices. Following unilateral lesions of the dorsal striatum, the
      rats exhibited an increased number of error trials, a bias to respond towards the
      ipsilateral side, a decreased accuracy on the contralateral side, and an increase
      of the execution time to respond correctly to contralateral stimuli. Striatal
      grafts alleviated the lateralised response deficits, prevented the development of
      lateral disparity, and restored the speed of responding back to pre-lesion
      levels. Control grafts of cortical tissues also increased task accuracy and
      reduced the ipsilateral bias in responding, but were without effect on the RT
      deficit.

PMID- 10078617
TI  - Discharge properties of single neurons in the dorsal nucleus of the lateral
      lemniscus of the rat.
AB  - The aim of the present study was to characterize the discharge properties of
      single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat.
      In the absence of acoustic stimulation, two types of spontaneous discharge
      patterns were observed: units tended to fire in a bursting or in a nonbursting
      mode. The distribution of units in the DNLL based on spontaneous firing rate
      followed a rostrocaudal gradient: units with high spontaneous rates were most
      commonly located in the rostral part of the DNLL, whereas in the caudal part
      units had lower spontaneous discharge rates. The most common response pattern of
      DNLL units to 200 ms binaural noise bursts contained a prominent onset response
      followed by a lower but steady-state response and an inhibitory response in the
      early-off period. Thresholds of response to noise bursts were on average higher
      for DNLL units than for units recorded in the inferior colliculus under the same
      experimental conditions. The DNLL units were arranged according to a mediolateral
      sensitivity gradient with the lowest threshold units in the most lateral part of
      the nucleus. In the rat, as in other mammals, the most common DNLL binaural input
      type was an excitatory response to contralateral ear stimulation and inhibitory
      response to ipsilateral ear stimulation (EI type). Pure tone bursts were in
      general a more effective stimulus compared to noise bursts. Best frequency (BF)
      was established for 97 DNLL units and plotted according to their spatial
      location. The DNLL exhibits a loose tonotopic organization, where there is a
      concentric pattern with high BF units located in the most dorsal and ventral
      parts of the DNLL and lower BF units in the middle part of the nucleus.

PMID- 10078618
TI  - The midbrain dopaminergic cell groups in the baboon Papio ursinus.
AB  - The present study evaluates the cytoarchitecture of midbrain dopaminergic regions
      in baboons using similar methodology to that recently applied to compare humans
      and rats. This information is relevant for the interpretation of nonhuman primate
      models of Parkinson's disease (PD). The midbrains of four alpha male baboons were
      serially sectioned into 10 evenly spaced series of 50 microm sections. Series
      were stained with either cresyl violet or immunohistochemically reacted for
      tyrosine hydroxylase, substance P, calbindin-D28k, or parvalbumin. The
      organization of dopaminergic cell groups and the distribution of proteins within
      these groups were found to be very similar to that previously described in humans
      [McRitchie et al., J. Comp. Neurol. 364:121-150; 1996]. Dorsal and ventral tiers
      of the A9 substantia nigra (SN) pars compacta and all divisions of the A8 and A10
      cell groups were identified revealing a high degree of homology in the
      arrangement of chemically distinct midbrain neurons between primates. The major
      difference between the organization of human and baboon midbrain dopaminergic
      neurons is the anteroposterior extent of the dense cell clusters within the SN
      pars compacta. In baboons the dorsomedial cell cluster is absent at posterior
      levels. The ventral tier cell clusters, which are targeted by PD in humans, are
      restricted to the posterior and ventral regions of the SN pars compacta of the
      baboon. In humans these cell clusters are found throughout the rostrocaudal
      extent of the SN. These ventral cell clusters have been previously shown to have
      reciprocal connections with sensorimotor regions of the putamen.

PMID- 10078619
TI  - Connections of the rostral ventral respiratory neuronal cell group: an
      anterograde and retrograde tracing study in the rat.
AB  - The connections of the rostral ventral respiratory cell group (VRG) were
      retrogradely and anterogradely determined after discrete injections of a mixture
      of the fluorescent tracers Fast Blue (FB) and Fluoro Ruby (FR) into the
      physiologically identified rostral inspiratory cell group. Retrogradely FB
      labeled neurons and/or anterogradely FR-labeled fibers and terminal fields were
      located bilaterally in a variety of brain areas. Both retrograde and anterograde
      labelings were mainly found in: 1) the deep cerebellar nuclei; 2) the lateral
      lemniscus and paralemniscal nuclei, deep gray, and white intermediate layers of
      the superior colliculus, tegmental (laterodorsal and microcellular) nuclei, and
      central gray; and 3) the septohypothalamic nucleus, and lateral and posterior
      hypothalamic areas. The FR-labeled terminal-like elements were found in: 1) Crus
      2 of the ansiform lobule, and the simple, 2, and 3 cerebellar lobules; 2) the
      subcoeruleus, deep mesencephalic, and Edinger-Westphal nuclei; and 3) the
      premammillary, lateral, and medial mammillary nuclei, retrochiasmatic part of the
      supraoptic nucleus, and the zona incerta. The FB-labeled neurons were found in:
      1) the parapedunculopontine tegmental and cuneiform nuclei, caudal linear nucleus
      of the raphe, and adjacent area of the cerebral peduncle; 2) the thalamic
      posterior nuclear group and subparafascicular, parafascicular, and gelatinosus
      thalamic nuclei; 3) the parastrial amygdaloid and subthalamic nuclei; and 4) the
      olfactory tubercle, granular, and agranular insular cortex, parietal and lateral
      orbital cortices. The connections of the rostral VRG with several cerebellar,
      midbrain, diencephalic, and telencephalic regions could provide an anatomical
      substrate for a role of these regions in the control of respiratory-related
      functions.

PMID- 10078620
TI  - GABA(A) receptor alpha4 subunit in DBA/2J and C57BL/6J mice.
AB  - GABA(A) receptors are chloride channels in the brain activated by binding of
      gamma-aminobutyric acid (GABA). Several important classes of drugs, including
      alcohol and certain antiepileptic drugs, modulate the actions of GABA. We report
      the sequence and expression of alpha4 subunits of GABA(A) receptors in two inbred
      strains of mice, DBA/2J and C57BL/6J, which differ in susceptibility to seizures
      and to behavioral effects of alcohol. We find no differences between the two
      strains in cDNA sequence, or in levels of alpha4 mRNA in whole brains of the two
      strains at 21 days of age, when DBA/2J are most susceptible to audiogenic
      seizures. We also describe the pattern of developmental expression and brain
      regional distribution of this subunit in mice, finding the highest developmental
      expression at about 14 days of age in whole brains, and the highest regional
      levels in hippocampus and basal forebrain (including thalamus) in adults.

PMID- 10078621
TI  - Intrinsic optical signals in vitro: a tool to measure alterations in
      extracellular space with two-dimensional resolution.
AB  - In excitable tissues, extensive neuronal activity or pathophysiological
      conditions, such as spreading depression, ischemic infarct, or epileptic seizure,
      are accompanied by changes in extracellular space volume. Extracellular space
      volume, in turn, influences neuronal excitability and extracellular ion
      concentrations and is, therefore, an important parameter of brain activity.
      Unfortunately, determination of changes in extracellular space by ion-selective
      microelectrodes is tedious, restricted to one spot in space at a time and limited
      in time resolution. In this study we present intrinsic optical signals in vitro
      as a tool to measure relative changes in extracellular space volume in brain
      slice preparations with two-dimensional spatial and sufficient time resolution.
      Evidence is given that the intensity of intrinsic optical signals is linearly
      correlated to the amplitude of extracellular space volume changes. In contrast,
      the optical signal is poorly correlated to the concomitant increase in
      extracellular potassium concentration. We conclude that intrinsic optical signals
      in vitro are a useful tool to measure the spread of changes in extracellular
      space volume with high resolution in time and space. In combination with the
      measurement of the extracellular space at one location using ion-selective
      microelectrodes, it is possible to calibrate the optical signal to percentile
      alterations of extracellular space volume.

PMID- 10078622
TI  - Procaine injection into the paraventricular nucleus reduces sympathetic and
      thermogenic activation induced by frontal cortex stimulation in the rat.
AB  - These experiments were designed to test the effect of procaine injection into the
      paraventricular nucleus on the sympathetic and thermogenic changes induced by
      frontal cortex stimulation. Oxygen consumption, firing rate of the sympathetic
      nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic
      temperatures (T(IBAT) and T(C)) were monitored in fasted male Sprague-Dawley rats
      before and 25 min after an electrical stimulation of the frontal cortex. The same
      variables were monitored in rats with administration of procaine into the
      paraventricular nucleus. The results show that cortical stimulation raises oxygen
      consumption, sympathetic neuron firing rates, T(IBAT), and T(C). This increase is
      reduced by procaine injection. These findings suggest that the paraventricular
      nucleus plays a key role in the sympathetic and thermogenic changes induced by
      cortical stimulation.

PMID- 10078623
TI  - Time-dependent effects of levodopa on regional brain dopamine metabolism and
      lipid peroxidation.
AB  - Levodopa treatment in Parkinson's disease has been suggested to contribute to
      disease progression through free radical generation. We compared the time course
      of levodopa-induced dopamine metabolism, and the resulting oxidative stress,
      between rat brain regions with varying dopaminergic innervation. At 1, 4, 8, and
      12 h after levodopa administration (100 mg/kg), dopamine, dihydroxyphenylacetic
      acid, and homovanillic acid were measured in striatum and ventral midbrain,
      regions containing marked dopaminergic innervation, and in prefrontal cortex and
      cerebellum, which possess little dopaminergic innervation. Malondialdehyde, a
      marker of oxidative stress, was measured in additional animals. The return of
      dopamine and its metabolites to control concentrations tended to be slower (by 3
      8 h) in cerebellum and prefrontal cortex than in dopaminergic regions.
      Malondialdehyde concentrations were decreased (p < 0.05) in ventral midbrain 8 h
      posttreatment, but increased in cerebellum 12 h posttreatment. We concluded that
      levodopa increases dopamine metabolism in nondopaminergic as well as dopaminergic
      regions, with delayed clearance of dopamine and its metabolites in
      nondopaminergic regions. The slower return of dopamine to control levels in
      nondopaminergic regions may be relevant to some of the side effects of levodopa.
      No support was found for the hypothesis that levodopa treatment induces oxidative
      stress.

PMID- 10078624
TI  - Predicting normal tissue response to radiotherapy.

PMID- 10078625
TI  - Diabetes mellitus: a predictor for late radiation morbidity.
AB  - PURPOSE: Given the high frequency of diabetes, as well as prostate cancer in the
      elderly population, we sought to determine whether diabetic patients treated with
      three-dimensional conformal external-beam radiotherapy (3DCRT) had an increased
      risk of late gastrointestinal (GI) or genitourinary (GU) complications. METHODS
      AND MATERIALS: Nine-hundred forty-four prostate cancer patients were treated
      between April 1989 and October 1996 using 3DCRT. Median patient age was 69 years
      (range 48-89), median center of prostate dose was 7211 cGy (range 6211-8074) and
      median follow-up was 36 months (range 2-99). Patients were evaluated every 6
      months with digital rectal examinations, serum PSAs and symptom questionnaires.
      Radiation morbidity was quantified using Radiation Therapy Oncology Group (RTOG)
      and modified Late Effects Normal Tissue Task Force (LENT) scales. Patients with a
      preexisting history of either Type I or Type II diabetes mellitus were coded as
      diabetics. RESULTS: One hundred twenty-one patients had diabetes (13% of total).
      Rates of acute morbidity did not differ between diabetics and nondiabetics;
      however, diabetics experienced significantly more late grade 2 GI toxicity (28%
      vs. 17%, p = 0.011) and late grade 2 GU toxicity (14% vs. 6%, p = 0.001). There
      was a trend toward increased late grade 3 and 4 GI complications in diabetics,
      but not for late grade 3 and 4 GU complications; however, the total number of
      recorded events for these categories was small. Examining the onset of late
      toxicity, diabetics developed GU complications earlier than nondiabetics (median:
      10 months vs. 24 months, p = 0.02). Considering age, dose, rectal blocking, field
      size, and history of diabetes in a stepwise multivariate regression model for
      late grade 2 GI toxicity, dose (p = 0.0001), diabetes (p = 0.0110), and rectal
      blocking (p = 0.0163) emerged independently predictive for complications. For
      late grade 2 GU toxicity, only the presence of diabetes remained independently
      significant (p = 0.0014). CONCLUSION: Diabetes mellitus is common in the elderly
      prostate cancer population. Diabetics are at a significant risk for the
      development of late grade 2 GI and GU complications after external-beam
      radiotherapy for prostate cancer. While diabetes, radiation dose, and rectal
      blocking predict for late GI complications, only the presence of diabetes
      influences late GU morbidity. Physicians may consider treatment modifications for
      diabetic patients, particularly those patients wishing to enter dose-escalation
      studies. Further study of the relationship between diabetes and late radiation
      complications is needed.

PMID- 10078626
TI  - Lack of correlation between residual radiation-induced DNA damage, in
      keratinocytes assayed directly from skin, and late radiotherapy reactions in
      breast cancer patients.
AB  - PURPOSE: To study the relationship between the severity of late reactions to
      radiotherapy in breast cancer patients, and the extent of residual radiation
      induced DNA damage, using a rapid assay of keratinocytes obtained directly from
      skin biopsies. METHODS AND MATERIALS: A review was made of 32 patients with
      breast cancer, treated uniformly by radiotherapy between 1983 and 1988, following
      breast-conserving surgery. Their late radiotherapy reactions were scored (9-14
      years post-radiotherapy) using a modified LENT SOMA scale, and a 5-mm buttock
      skin punch biopsy was obtained. Intact skin was irradiated at room temperature,
      and after allowing 24 h for repair, the tissue was disaggregated and the cells
      processed for pulsed field gel electrophoresis (PFGE). Residual DNA damage was
      expressed as the fraction of DNA released (FDR) following 150 Gy. RESULTS:
      Studies using flow cytometry on disaggregated breast skin showed that over 90% of
      the cells were keratinocytes. The PFGE assay was robust with low background FDRs
      in unirradiated skin samples (mean 3.2%) and a wide range of FDRs following
      irradiation from 11.5% to 26.6%. No correlation was found between the FDR at 150
      Gy (FDR 150) and any of the late reaction scores or retrospective acute reaction
      scores. There was, however, a borderline significant correlation for family
      history and FDR 150 (p = 0.059). CONCLUSION: Rapid measurement of residual DNA
      damage in irradiated differentiated keratinocytes, the predominant cell
      population in skin biopsies, showed no correlation with the severity of
      symptomatic early or documented late reactions in a retrospectively studied group
      of 32 breast cancer patients.

PMID- 10078627
TI  - Abnormalities by pulmonary regions studied with computer tomography following
      local or local-regional radiotherapy for breast cancer.
AB  - PURPOSE: To study pulmonary radiological abnormalities with computer tomography
      (CT) following different radiotherapy (RT) techniques for breast cancer with
      respect to regions and density, and their correlation to pulmonary complications
      and reduction in vital capacity (VC). METHODS AND MATERIALS: CT scans of the
      lungs were performed prior to and 4 months following RT in 105 breast cancer
      patients treated with local or local-regional RT. The radiological abnormalities
      were analyzed with a CT-adapted modification of a classification system
      originally proposed by Arriagada, and scored according to increasing density (0
      3) and affected lung regions (apical-lateral, central-parahilar, basal-lateral).
      The highest density grade in each region were added together to form scores
      ranging from 0-9. The patients were monitored for RT-induced pulmonary
      complications. VC was measured prior to and 5 months following RT. RESULTS:
      Increasing CT scores were correlated with both local-regional RT and pulmonary
      complications (p < 0.001). The mean reduction of VC for patients scoring 4-9 (
      202 ml) was larger than for patients scoring 0-3 (-2 ml) (p = 0.035). The effect
      of confounding factors on the radiological scoring was tested in the local
      regional RT group. Scores of 4-9 were less frequently seen in the patients who
      had received adjuvant chemotherapy prior to RT. The importance of the respective
      lung regions on the outcome of pulmonary complications was tested. Only
      radiological abnormalities in the central-parahilar and apical-lateral regions
      were significantly correlated to pulmonary complications. DISCUSSION:
      Radiological abnormalities detected on CT images and scored with a modification
      of Arriagada's classification system can be used as an objective endpoint for
      pulmonary side effects in breast cancer. The described model should, however, be
      expanded with information about the volume of lung affected in each region before
      definite conclusions can be drawn concerning each region's relative importance
      for the development of pulmonary complications. The negative association between
      sequential chemotherapy and radiological abnormalities should be confirmed in
      future studies.

PMID- 10078628
TI  - Total body irradiation correlates with chronic graft versus host disease and
      affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA
      identical allogeneic bone marrow transplant.
AB  - PURPOSE: To investigate whether different procedure variables involved in the
      delivery of fractionated total body irradiation (TBI) impact on prognosis of
      patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone
      marrow transplant (BMT). METHODS AND MATERIALS: Ninety-three consecutive patients
      with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT
      between 1 August 1983 and 30 September 1995 were conditioned with the same
      protocol consisting of cyclophosphamide and fractionated TBI. The planned total
      dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period,
      variations in delivering TBI schedule occurred with regard to used radiation
      source, instantaneous dose rate, technical setting, and actual total dose
      received by the patient. We tested these different TBI variables as well as
      factors related to patient, state of disease, and transplant-induced disease to
      investigate their influence on transplant-related mortality, leukemia relapse,
      and survival. RESULTS: At median follow-up of 7 years (range 3-15 years) the
      probabilities of leukemia-free survival (LFS) and overall survival (OS) for the
      93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft
      versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p
      = 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd
      (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors
      affecting overall survival. The occurrence of chronic GvHd was correlated with
      actually delivered TBI dose (p = 0.04). Combined stratification of prognostic
      factors showed that patients who received the planned total dose of TBI (12 Gy)
      and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and
      OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence
      of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients
      transplanted in first remission (p = 0.05). At multivariate analysis, TBI dose
      was an independent factor affecting overall survival (p = 0.05) as well as
      chronic GvHd (p = 0.001) and age (p = 0.04). CONCLUSIONS: This retrospective
      analysis showed that different variables involved in TBI delivery may influence
      the occurrence of cGvHd and affect prognosis of patients with ALL receiving
      allogeneic BMT. The total dose of 12 Gy, administered in six fractions over 3
      days, appears to be an effective and low toxic regimen for ALL patients
      transplanted in first remission.

PMID- 10078629
TI  - Addition of chemotherapy to radiation therapy alters failure patterns by cell
      type within non-small cell carcinoma of lung (NSCCL): analysis of radiation
      therapy oncology group (RTOG) trials.
AB  - PURPOSE: To evaluate the influence of cell type within non-small cell carcinoma
      of lung (NSCCL) on failure patterns when chemotherapy (CT) is combined with
      radiation therapy (RT). METHODS AND MATERIALS: Data from 4 RTOG studies including
      1415 patients treated with RT alone, and 5 RTOG studies including 350 patients
      also treated with chemotherapy (RT + CT) were analyzed. Patterns of progression
      were evaluated for squamous cell carcinoma (SQ) (n = 946), adenocarcinoma (AD) (n
      = 532) and large cell carcinoma (LC) (n = 287). RESULTS: When treated with RT
      alone, SQ was more likely to progress at the primary site than LC (26% vs. 20%, p
      = 0.05). AD and LC were more likely to progress in the brain than SQ (20% and 18%
      vs. 11%, p = 0.0001 and 0.011, respectively). No differences were found in
      intrathoracic and distant metastasis by cell type. When treated with RT + CT, AD
      was less likely to progress at the primary than either SQ or LC (23% vs. 34% and
      40%, respectively; p = 0.057 and 0.035). AD was more likely than SQ to
      metastasize to the brain (16% vs. 8%, p = 0.03), and other distant sites (26% vs.
      14%,p = 0.019). No differences were found in intrathoracic metastasis. LC
      progressed at the primary site more often with RT + CT than with RT alone (40%
      vs. 20%, p = 0.036). Death with no clinical progression was more likely with SQ
      than AD or LC for RT alone and RT + CT (p < 0.01). Brain metastasis was altered
      little by the addition of CT, but other distant metastases were significantly
      decreased (p < 0.001) in all cell types by the addition of CT. CONCLUSION: CT,
      although effective in reducing distant metastasis in all types of NSCCL, has
      different effects on the primary tumor by cell type, and has no effect on brain
      metastasis or death with no progression. Different treatment strategies should be
      considered for the different cell types to advance progress with RT + CT in
      NSCCL.

PMID- 10078630
TI  - Factors influencing the outcome of radiotherapy in malignant mesothelioma of the
      pleura--a single-institution experience with 189 patients.
AB  - PURPOSE: To determine the factors influencing the response to palliative
      radiotherapy (RT) in malignant mesothelioma of the pleura (MM). METHODS AND
      MATERIALS: A retrospective review was conducted of the records of all patients
      with mesothelioma who were referred to our institution between 1979 and 1996. A
      total of 227 RT series were administered to 189 patients with MM. Of these, 21
      patients with chest wall nodules also received concomitant local hyperthermia.
      RESULTS: The median survival was 5 months from the start of RT and only 17% of
      patients were alive at 1 year after treatment. Chest pain and painful chest wall
      metastases were the main indications for RT. A higher local response rate was
      seen for patients treated with a 4-Gy per fraction scheme, vs. those receiving
      fractions of less than 4 Gy (50% vs. 39%). Pain recurrence occurred predominantly
      within the previous RT field, and pain recurred after a median of 69 days (range
      32-363) in the group treated using 4-Gy fractions. When compared with a matched
      group, patients treated with combined RT and hyperthermia had higher response
      rates and fewer in-field recurrences. CONCLUSIONS: RT provides local palliation
      in at least 50% of patients with MM who were treated using a 4-Gy/fraction scheme
      to a median dose of 36 Gy. The low response rates with RT alone suggest that
      combined RT and local hyperthermia should be further evaluated in MM.

PMID- 10078631
TI  - Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial
      of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation
      for squamous cell carcinoma of the esophagus.
AB  - PURPOSE: To determine the outcome of neoadjuvant chemotherapy followed by
      concurrent chemotherapy plus high-dose radiation therapy in patients with
      local/regional squamous cell carcinoma of the esophagus. METHODS AND MATERIALS:
      Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were
      entered on a prospective single-arm study, of which 38 were eligible. Patients
      received 3 monthly cycles of 5-FU (1000 mg/m2/24 h x 5 days) and cisplatin (100
      mg/m2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU
      (1000 mg/m2/24 h x 5 days) and cisplatin (75 mg/m2 day 1) plus concurrent 6480
      cGy (combined modality segment). The median follow-up in surviving patients was
      59 months. RESULTS: For the 38 eligible patients, the primary tumor response rate
      was 47% complete, 8% partial, and 3% stable disease. The first site of clinical
      failure was 39% local/regional and 24% distant. For the total patient group,
      there were 6 deaths during treatment, of which 9% (4/45) were treatment related.
      The median survival was 20 months. Actuarial survival at 3 years was 30%, and at
      5 years, 20%. CONCLUSION: This intensive neoadjuvant approach does not appear to
      offer a benefit compared with conventional doses and techniques of combined
      modality therapy. However, high dose radiation (6480 cGy) appears to be
      tolerable, and is being tested further in Intergroup Trial INT 0123.

PMID- 10078632
TI  - Optimum fractionation for high-dose-rate endoesophageal brachytherapy following
      external irradiation of early stage esophageal cancer.
AB  - PURPOSE: To establish the optimum fractionation for high-dose-rate (HDR)
      endoesophageal brachytherapy (EBT) for early stage esophageal cancer from
      retrospective data of patients treated with different HDR schedules following
      external beam irradiation (EBI). METHODS AND MATERIALS: The study population
      consisted of 35 consecutive early stage esophageal cancer patients who received
      EBI to the mediastinum, plus EBT, between May 1992 and November 1995 at the
      Hiroshima University Medical Center and Hiroshima City Hospital. All patients
      were treated with EBI, with doses ranging from 50 to 61 Gy. The spinal cord was
      spared after 44-45 Gy. HDR EBT was performed using a double-balloon applicator in
      conjunction with an Ir-192 remote afterloading system. One group of 10 patients
      was given a weekly endoesophageal boost of 4 or 5 Gy at a distance of 5 mm from
      the applicator surface over a period of 1-2 weeks. Another group of 25 patients
      was treated with 4 or 5 endoesophageal boosts with a fraction dose of either 2.5
      or 2 Gy for 1 week. The linear quadratic (LQ) formula was used to calculate the
      biologically effective dose (BED) for tumor (Gy10) and esophageal mucosa (Gy3);
      Gy10 means alpha/beta equals 10 Gy, and Gy3 means alpha/beta equals 3 Gy. The
      Kaplan-Meier method was used to calculate the local control and late complication
      rates, while the Cox-Mantel test was used to evaluate statistical significance (p
      < 0.01). RESULTS: Nine (26%) of the 35 patients recurred locally and 7 (20%) had
      late complications (esophageal ulcer grade by RTOG/EORTC criteria > 1). The 5
      year overall survival, local control, and late complication rates were 38%, 57%,
      and 26%, respectively. The probability of local recurrence was not affected by
      the treatment parameters. Results from the LQ formula significantly correlate
      with data on late complications. A BED > 134 Gy3 and a fraction number = < 3 were
      associated with late complications (grade > 1). BED analysis showed that the
      fractionation dose should be decreased to 2.5 or 2.0 Gy at a distance of 5 mm
      from the applicator surface, and the number of doses increased to 4 or 5,
      respectively, to yield a satisfactory BED (< 134 Gy3). CONCLUSION: A significant
      reduction in endoesophageal brachytherapy dose per fraction is necessary to
      reduce late complications. Our current treatment protocol for early-stage
      esophageal cancer consists of EBI of 60 Gy followed by 4 EBT doses at a fraction
      dose of 2.5 Gy applied over 1 week.

PMID- 10078633
TI  - Results of external beam radiotherapy alone for incompletely resected carcinoma
      of rectosigmoid or rectum: Peter MacCallum Cancer Institute experience 1981-1990.
AB  - PURPOSE: To study the results of external beam radiotherapy treatment for
      incompletely resected nonmetastatic rectosigmoid and rectal carcinoma. METHODS
      AND MATERIALS: A retrospective review was carried out of all patients (57)
      presenting to Peter MacCallum Cancer Institute from 1981 to 1990 with
      incompletely resected nonmetastatic rectosigmoid or rectal cancer who were
      treated with external beam radiotherapy. Three radiotherapy schedules were used:
      radical (50 to 60 Gy, 27 patients), high-dose palliative (45 Gy, 25 patients),
      and low-dose palliative (less than 45 Gy, 5 patients). Symptomatic response,
      overall survival, and the effect of prognostic factors on treatment outcome were
      evaluated. The median follow-up period for survivors was 49 months. RESULTS:
      Symptomatic response rates were 83% and 79% for the radical and high-dose
      palliative groups respectively. The estimated median survival time from
      presentation for all patients was 16.4 months (radical 26.1 months, high-dose
      palliative 15.7 months). Patients with microscopic residual disease survived
      significantly longer than patients with macroscopic residual disease (estimated
      median survival time 30.7 months vs. 14.3 months, p = 0.013). CONCLUSIONS: No
      dose response effect was seen between the radical group and high-dose palliative
      group. Microscopic residual disease at presentation was the only significant
      predictor of better survival. The conventionally fractionated course of 50 to 60
      Gy was not significantly better in terms of palliation and overall survival than
      a shorter palliative course of 45 Gy. In future, preoperative chemoradiation
      should improve outcome by reducing the number of patients with incompletely
      resected cancer.

PMID- 10078634
TI  - Five fractions of preoperative radiotherapy for selected cases of rectal
      carcinoma: long-term tumor control and tolerance to treatment.
AB  - BACKGROUND: Randomized Swedish studies demonstrate the efficacy of a 5-fraction
      course of preoperative radiotherapy for rectal carcinoma. The present study
      evaluates the results in a single U.S. institution over a 20-year period with a
      similar regimen. METHODS AND MATERIALS: During the period of 1975-1995, 83
      patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate
      surgery for rectal cancer. These patients represented 21% of cases receiving
      preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5
      fraction course was used for lesions deemed readily resectable but too bulky for
      conservative endocavitary treatment. Since 1990, it has been our policy to
      administer postoperative chemotherapy to medically fit patients who prove to have
      pathologic Stage II or III disease. Patient characteristics including age (mean
      65 years, range 23-90), gender (45% male), and location within the rectum were
      comparable to our previously reported cases that received 45 Gy/25 fractions
      preoperatively. However, the group selected for 5 fractions preoperatively had
      relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11%
      vs. 20%), or near obstructing (1% vs. 16%). RESULTS: With a post treatment follow
      up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant
      failures, with an actuarial local control of 95%, and disease-specific survival
      of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred
      in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III
      disease was found in 56% of the cases, 74% of which were free of disease at last
      follow-up. However, patients with Stage II or III lesions that were significantly
      tethered or fixed had a 40% greater likelihood of recurring than similar stage
      lesions that were, at most, slightly tethered. Sphincter-preserving surgery was
      possible in 60% of the patients. In recent years, postoperative chemotherapy has
      been administered to 16 patients with Stage II or III disease; this has been well
      tolerated, with only 1 late toxicity (cystitis managed medically). When compared
      with a matched group of cases receiving conventionally fractionated preoperative
      radiation, there were no significant differences in perioperative morbidity and
      nonradiotherapeutic cost generating factors (length of hospital stay, duration of
      postoperative antibiotics, blood loss at surgery). CONCLUSION: Patients with
      resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy
      to the pelvis had excellent local and distant control of disease. These patients
      were able to undergo sphincter-preserving surgery and postoperative chemotherapy.
      It would be of interest to conduct a randomized trial comparing short course with
      longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions.
      The results of this study suggest that, in general, differences in toxicity,
      local control, and disease-free survival would probably be < 10%. However, since
      the results of this study suggest that patients with significantly tethered
      lesions may be better served with the higher dose and longer duration course of
      radiation, clinical degree of fixation should be included as a stratification
      parameter, and stopping criteria should be included for tethered lesions.

PMID- 10078635
TI  - Linear accelerator radiosurgery for nonacoustic schwannomas.
AB  - PURPOSE: To analyze the results of nonacoustic schwannomas treated with linear
      accelerator stereotactic radiosurgery. METHODS AND MATERIALS: Between August 1989
      and October 1997, 18 patients with nonacoustic schwannomas underwent stereotactic
      radiosurgery at the University of Florida. Nine patients had schwannomas located
      in the jugular foramen region, seven in the trigeminal nerve, and two in the
      facial nerve. Nine patients had initial subtotal resections and nine did not
      undergo surgical intervention. One of the 9 patients with subtotal resection was
      treated with radiosurgery for a recurrent tumor. Tumor volumes ranged from 0.7 to
      15.4 cm3 with a mean volume of 5.5 cm3. Minimal tumor doses ranged from 10.0 to
      15.0 Gy with a mean dose of 13.1 Gy. Treatment dose was specified to the 80%
      isodose shell in 11 patients (58%) and to the 70% isodose shell in the remaining
      patients. Ten patients (56%) were treated with a single isocenter, 6 patients
      (33%) with 2-4 isocenters, and 2 patients (11%) with greater than 5 isocenters.
      Follow-up ranged from 5 to75 months and the mean follow-up was 32 months. Ten
      patients (56%) had follow-up beyond 2 years and none were lost to follow-up.
      Local control was defined as clinically stable neurological status and/or stable
      or decreased tumor size on yearly follow-up MR imaging. RESULTS: Eighteen
      evaluable patients (100%) had local control after treatment. All were alive and
      progression-free at last follow-up. Six of 10 patients with follow-up MRI 2 years
      or more after treatment had tumor regression and 4 patients had stable disease.
      Three additional patients with an MRI at 1 year showed no tumor change. Four
      complications in 3 patients included one worsening of a preexisting VII nerve
      palsy, 2 patients with new onset of hearing loss, and one with ataxia. No
      surgical intervention or prolonged steroid use was necessary for any patient with
      complications. Five patients had improvement in preexisting neurologic deficits.
      CONCLUSIONS: Excellent preliminary tumor control rates and a favorable toxicity
      profile support the effectiveness of linear accelerator stereotactic radiosurgery
      for patients with nonacoustic schwannomas.

PMID- 10078636
TI  - Radiosurgery for brain metastases: is whole brain radiotherapy necessary?
AB  - PURPOSE: Because whole brain radiotherapy (WBRT) may cause dementia in long-term
      survivors, selected patients with brain metastases may benefit from initial
      treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We
      reviewed results of RS +/- WBRT in patients with newly diagnosed brain metastasis
      to provide background for a prospective trial. METHODS AND MATERIALS: Patients
      with single or multiple brain metastases managed initially with RS alone vs. RS +
      WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively
      reviewed. The use of upfront WBRT depended on physician preference and referral
      patterns. Survival, freedom from progression (FFP) endpoints, and brain control
      allowing for successful salvage therapy were measured from the date of diagnosis
      of brain metastases. Actuarial curves were estimated using the Kaplan-Meier
      method. Analyses to adjust for known prognostic factors were performed using the
      Cox proportional hazards model (CPHM) stratified by primary site. RESULTS:
      Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival
      11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively).
      Brain FFP (scoring new metastases and/or local failure) was significantly worse
      for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjustedp = 0.03 and
      hazard ratio = 0.476). However, brain control allowing for successful salvage of
      a first failure was not significantly different for RS alone vs. RS + WBRT (62%
      vs. 73% at 1 year; CPHM adjusted p = 0.56). CONCLUSIONS: The omission of WBRT in
      the initial management of patients treated with RS for up to 4 brain metastases
      does not appear to compromise survival or intracranial control allowing for
      salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to
      assess survival, quality of life, and cost in good-prognosis patients with newly
      diagnosed brain metastases.

PMID- 10078637
TI  - Primary central nervous system non-Hodgkin's lymphoma (PCNSL): survival
      advantages with combined initial therapy? A final report of the North Central
      Cancer Treatment Group (NCCTG) Study 86-72-52.
AB  - PURPOSE: We herein report updated survival and toxicity data on the entire cohort
      of 53 eligible patients treated on North Central Cancer Treatment Group (NCCTG)
      protocol 86-72-52, which is now closed. METHODS AND MATERIALS: An initial report
      was published in this journal in 1995. No substantive changes in the conclusions
      of that report were identified in this analysis. Median survival was 9.6 months
      for the entire cohort; median survival for the 20 patients who completed the
      prescribed protocol treatment was 20.7 months. The hematologic and non
      hematologic toxicity distributions are virtually the same as those reported in
      the original paper. RESULTS: Results are given for the entire group and for
      subsets defined by age < or = 60 versus > 60 years, and < 70 versus > or = 70
      years of age. CONCLUSIONS: No significant differences were observed in any of the
      outcome variables by age group. There was, however, a nonsignificant suggestion
      of poorer outcome in those who were > 60 years of age.

PMID- 10078638
TI  - Transperineal 125iodine implantation for treatment of clinically localized
      prostate cancer: 5-year tumor control and morbidity.
AB  - PURPOSE: To evaluate the efficacy and toxicity of transperineal 125I implants for
      clinically localized prostate cancer in elderly men in a community cancer
      setting. METHODS AND MATERIALS: From 1988 to 1993, 206 patients, median age 77
      years, with localized (Stage T1 and T2), low-grade (Gleason score < or = 7)
      prostate cancer were treated using pre-planned 125I transperineal implants.
      Patients were followed for biochemical freedom from disease, overall survival,
      and treatment-associated morbidity. RESULTS: The 5-year actuarial biochemical
      freedom from failure rate for all patients available for follow-up was 63%.
      Specifically, biochemical freedom from failure was 76% in patients with
      pretreatment PSA < or = 10 ng/ml, compared to 51% of patients with values > 10
      ng/ml (median observation time 35 months). Actuarial freedom from failure for
      patients with PSA < or = 4 ng/ml was 84%. Stage and Gleason score did not predict
      outcome. PSA nadir was the strongest predictor of long-term biochemical disease
      free survival (p < 0.001) with only 2 failures in 62 patients who achieved a
      posttreatment PSA nadir < or = 0.5 ng/ml. CONCLUSION: Transperineal 125I implants
      for early prostate cancer are efficacious and feasible for certain populations of
      elderly patients with favorable prognostic indicators in the community cancer
      setting. Patients with poor prognostic indicators at diagnosis do not appear to
      be candidates for treatment with implant alone. ( 1999 El.vit r 'Cio;noo lnc

PMID- 10078639
TI  - Use of three-dimensional radiation therapy planning tools and intraoperative
      ultrasound to evaluate high dose rate prostate brachytherapy implants.
AB  - PURPOSE: We performed a pilot study to evaluate the quality of high dose rate
      (HDR) prostate implants using a new technique combining intraoperative real-time
      ultrasound images with a commercially available 3-dimensional radiation therapy
      planning (3D RTP) system. METHODS AND MATERIALS: Twenty HDR prostate implants
      performed by four different physicians on a phase I/II protocol were evaluated
      retrospectively. Radiation therapy (RT) consisted of pelvic external beam RT
      (EBRT) to a dose of 46 Gy in 2-Gy fractions over 5 weeks and 2 HDR implants
      (prescribed dose of 950 cGy per implant). Our in-house real-time geometric
      optimization technique was used in all patients. Each HDR treatment was delivered
      without moving the patient. Ultrasound image sets were acquired immediately after
      needle placement and just prior to HDR treatment. The ultrasound image sets,
      needle and source positions and dwell times were imported into a commercial
      computerized tomography (CT) based 3D RTP system. Prostate contours were outlined
      manually caudad to cephalad. Dose-volume histograms (DVHs) of the prostate were
      evaluated for each implant. RESULTS: Four patients with stage T2a carcinoma, 4
      with stage T2b, and 3 with stage T1c were studied. The median number of needles
      used per implant was 16 (range 14-18). The median treated volume of the implant
      (volume of tissue covered by the 100% isodose surface) was 82.6 cc (range 52.6
      96.3 cc). The median target volume based on the contours entered in the 3D RTP
      system was 44.83 cc (range 28.5-67.45 cc). The calculated minimum dose to the
      target volume was 70% of the prescribed dose (range 45-97%). On average 92% of
      the target volume received the prescribed dose (range 75-99 %). The mean
      homogeneity index (fraction of the target volume receiving between 1.0 to 1.5
      times the prescribed dose) was 80% or 0.8 (range 0.55-0.9). These results compare
      favorably to recent studies of permanent implants which report a minimum target
      volume dose of 43% (range 29-50%) and an average of 85% of the target volume
      (range 76-92%) receiving the prescribed dose. CONCLUSIONS: The feasibility of
      evaluating HDR prostate implants using ultrasound images (acquired immediately
      prior to treatment) with a commercially available 3D RTP system was established.
      The dosimetric characteristics of these HDR implants appear to be substantially
      different compared to permanent implants. These developments allow quantitative
      evaluation of the dosimetric quality of HDR prostate treatments. Future studies
      will examine any correlation between the dosimetric quality of the implant and
      clinical/biochemical outcomes.

PMID- 10078640
TI  - Use of pelvic CT scanning to evaluate pubic arch interference of transperineal
      prostate brachytherapy.
AB  - PURPOSE: To determine the necessity of preoperative evaluation of pubic arch
      interference in patients with small prostate volumes. METHODS AND MATERIALS: CT
      scans from 97 consecutive, unselected patients with stage T1 or T2 prostatic
      carcinoma who had transperineal I-125 or Pd-103 implants at the University of
      Washington in 1997 were analyzed for pubic arch interference. Transrectal
      ultrasound (TRUS) was performed with 6.0-MHz transducer with the patient in the
      lithotomy position and the patient's thighs vertical, similar to that used during
      the implant procedure. CT scans were obtained with the patient in the supine
      position, with 0.5-cm images taken at every 0.5 cm. To check for potential arch
      interference, the largest prostate cross-section was overlaid on the narrowest
      portion of the pubic arch. The overlap of the pubic arch and the prostate margin
      is measured at right angles to the inner pubic surface. The prostate volume
      obtained from the TRUS images was compared with the degree of pubic arch
      interference in order to determine whether TRUS volume predicted for
      interference. RESULTS: There was considerable variability in pubic arch
      interference between patients. The mm of pubic arch overlap with the prostatic
      margin varied from -11 mm to 20 mm. Patients with larger prostate volumes
      generally had more pubic arch interference, but the degree of interference was
      only loosely related to the prostate volume (r = 0.46). CONCLUSIONS: The degree
      of pubic arch interference is highly variable from one patient to the next and
      the TRUS volume cannot reliably predict patients who do or do not need a pelvic
      CT to detect potential arch interference.

PMID- 10078641
TI  - Use of TRUS to predict pubic arch interference of prostate brachytherapy.
AB  - PURPOSE: To demonstrate the potential for transrectal ultrasound (TRUS) to
      predict pubic arch interference of transperineal needle placement for prostate
      brachytherapy. METHODS AND MATERIALS: TRUS and pelvic computerized tomography
      (CT) scans from 22 patients who had transperineal prostate brachytherapy at
      University of Washington were analyzed for pubic arch visualization and
      interference. The outer margins of the prostate and the inner margins of the
      pubic bones from each imaging modality were outlined and compared. RESULTS: The
      pubic arch was readily visualized by TRUS in 21 of the 22 patients. There was
      good correlation between TRUS and CT for evaluating the amount of pubic arch
      interference (r = 0.90). CONCLUSION: TRUS can be substituted for CT imaging to
      evaluate pubic arch interference of transperineal needle placement for prostate
      brachytherapy. Eliminating routine CT scanning would reduce the cost of
      treatment.

PMID- 10078642
TI  - Defining the implant treatment volume for patients with low risk prostate cancer:
      does the anterior base need to be treated?
AB  - PURPOSE: An increased incidence of acute urinary retention has been reported
      after interstitial prostate radiation therapy when the anterior base of the
      prostate gland receives 100% of the prescription dose. The frequency of prostate
      cancer in this location as a function of the pre-treatment prostate specific
      antigen (PSA), biopsy Gleason score, and 1992 American Joint Commission on Cancer
      Staging (AJCC) was determined. METHODS AND MATERIALS: One hundred four men
      treated at the Brigham and Women's Hospital with radical prostatectomy for
      clinically localized prostate cancer between 1995-1996 comprised the study
      population. Prostatectomy specimens were whole mounted and the location of each
      tumor foci enumerated. RESULTS: Of 269 foci of prostate cancer found in 39 low
      risk prostate cancer patients (PSA < 10 ng/ml, biopsy Gleason score < or = 6, and
      1992 AJCC clinical stage T1c,2a), a single focus (0.37%) was noted in the
      anterior base. Conversely, 20/355 (5.6%) and 18/251 (7.2%) tumor foci were noted
      in the anterior base in 43 patients with intermediate risk and 24 patients with
      high-risk disease, respectively. CONCLUSIONS: A new definition of the treatment
      volume excluding the anterior base for low-risk prostate cancer patients may be
      justified.

PMID- 10078643
TI  - Skin cancer of the head and neck with incidental microscopic perineural invasion.
AB  - PURPOSE: To address outcomes in clinically asymptomatic patients in whom the
      unexpected finding of microscopic perineural invasion is noted at the time of
      surgery. METHODS AND MATERIALS: The 35 patients included in this study had skin
      cancers of the head and neck treated with curative intent between January 1965
      and April 1995 at the University of Florida. All patients were without clinical
      or radiographic evidence of perineural invasion but, at the time of biopsy or
      surgical excision, had the incidental finding of microscopic perineural invasion.
      Definitive therapy consisted of radiotherapy alone after lesion biopsy (3
      patients) or surgical excision preceded (2 patients) or followed (30 patients) by
      radiotherapy. All patients had follow-up for at least 1 year, 13 patients (37%)
      had follow-up for at least 5 years. RESULTS: The 5-year local control rate was
      78%. The 5-year local control rate for the few patients treated with radiotherapy
      alone was statistically similar to that for patients treated with surgery and
      radiotherapy (100% vs. 77%, p = 0.4). Multivariate analysis for factors affecting
      local control included sex, histology, age, treatment group, clinical T stage,
      initial histologic differentiation, and previously untreated vs. recurrent
      tumors, none of which was found to be significant. CONCLUSIONS: Both surgery plus
      radiotherapy and radiotherapy alone provide a relatively high rate of local
      control for patients with incidentally discovered perineural invasion secondary
      to skin cancer.

PMID- 10078644
TI  - Postoperative irradiation of pterygium with 90Sr eye applicator.
AB  - PURPOSE: Pterygium are triangular growths of fibrovascular tissue of the bulbar
      conjunctiva that ultimately cause visual disturbances. Surgical removal is the
      initial treatment of choice for pterygium, but the recurrence rate after excision
      alone is 20-40%. The purpose of this paper is to reaffirm the effectiveness of
      postoperative irradiation with a 90Sr eye applicator. METHODS AND MATERIALS: From
      1993 to 1996, 361 patients (393 lesions) were treated with 90Sr postoperative
      radiation therapy. Forty-five lesions were recurrent cases. All cases had been
      excised using the "bare sclera" method. Postoperative radiation performed within
      48 h after surgery received radiation doses of 30 Gy, the others received doses
      of 35 Gy, using the 90Sr eye applicator. RESULTS: Thirty-four (8.6%) of the 393
      lesions recurred. The overall 1-year local control rate was 93.7%. Seventy-one
      percent of the recurrent cases were noticed within 1.5 years after treatment. The
      multivariate analysis for total cases demonstrated that sex, age, prior
      treatment, and duration of pterygium affected the overall local control rate. No
      complications from this treatment have been observed. CONCLUSION: It was
      reconfirmed that postoperative irradiation was effective in preventing local
      recurrence after surgical removal of pterygium.

PMID- 10078645
TI  - Distinct mathematical behavior of apoptotic versus non-apoptotic tumor cell
      death.
AB  - PURPOSE: The presence or absence of a p53-dependent apoptosis response has
      previously been shown to greatly influence radiosensitivity in tumor cells. Here,
      we examine clonogenic survival curves for two genetically related oncogene
      transformed cell lines differing in the presence or absence of p53 and apoptosis.
      Solid tumor radiosensitivity patterns have been previously described for these
      lines. MATERIALS AND METHODS: Oncogene-transformed fibroblasts derived from E1A +
      Ras transfection of p53-wild-type or p53-null mouse embryonic fibroblasts were
      plated as single cells and irradiated at increasing radiation doses in single
      fractions from 1.5 to 11 Gy. Clonogenic cell survival assays were obtained.
      Survival data are fit to a linear-quadratic relationship: S = e(-alphaD-betaD2).
      Apoptosis was assessed and quantitated morphologically by staining with the
      fluorescent nuclear dye DAPI, by TUNEL assay for DNA fragmentation, and by
      measurement of apoptotic cysteine protease cleavage activity in cytosolic
      extracts. RESULTS: Whereas radiation triggers massive apoptosis in the presence
      of p53, it produces no measurable DNA fragmentation, apoptotic cysteine protease
      cleavage activity, or morphological changes of apoptosis in the cells lacking
      p53. These contrasting mechanisms of death display dramatically different
      quantitative behavior: log-survival of apoptotic cells is linearly proportional
      to dose (S = e(-alphaD)), whereas survival of non-apoptotic (p53 null) is linear
      quadratic with a significant quadratic contribution. The surviving fraction at 2
      Gy (SF-2) for p53-null cells was 70% verses 12% for p53-intact cells.
      CONCLUSIONS: In this system, apoptosis appears to exhibit a dominance of single
      event which produces a very high alpha/beta ratio, and no significant shoulder;
      whereas non-apoptotic death in this system exhibits a comparatively small linear
      component, a low alpha/beta ratio, and a larger shoulder.

PMID- 10078646
TI  - The effects of combining ionizing radiation and adenoviral p53 therapy in
      nasopharyngeal carcinoma.
AB  - PURPOSE: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck
      region, with a 5-year survival level of approximately 65%. To explore gene
      therapy as a novel approach which might improve outcome, we have shown previously
      that introduction of human recombinant wild-type p53 mediated by the adenoviral
      vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC)
      cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether
      this strategy, combined with ionizing radiation (XRT), was more effective than
      either treatment alone. METHODS AND MATERIALS: CNE-1, CNE-2Z, and a normal human
      nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming
      units (pfu)/cell of Ad5CMV-p53, respectively. These doses were isoeffective for
      beta-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered
      24 h post-infection, and Western blot analyses were conducted for p53,
      p21WAF1/CIP1, bax, and bcl-2 2 days after XRT. Cell survival was assessed using a
      clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using
      DNA agarose gel electrophoresis, and cell cycle was analyzed using flow
      cytometry. RESULTS: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy)
      resulted in an approximately 1-log greater level of cytotoxicity compared to that
      observed with XRT alone for both NPC cell lines. The two modalities appear to be
      interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts.
      XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone
      induced significant recombinant p53 expression, which was not further enhanced by
      the addition of XRT. Similar observations were made for p21WAF1/CIP1 expression.
      No changes were observed for bax or bcl-2 expression with any of these
      treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed
      after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that
      Ad5CMV-p53 infection did not perturb the cell cycle beyond that observed with XRT
      alone. CONCLUSION: p53 gene therapy and XRT appears to interact in a synergistic
      manner; underscoring the significant potential of this novel strategy in the
      treatment of NPC.

PMID- 10078647
TI  - Repopulation characteristics and cell kinetic parameters resulting from multi
      fraction irradiation of xenograft tumors in SCID mice.
AB  - PURPOSE: Cell kinetics and repopulation rates during multifraction irradiation
      have previously been measured in SiHa human cervical carcinoma cells grown as
      spheroids. The current study applied similar techniques to SiHa tumor xenografts
      with the ultimate goal of assessing the clinical prognostic value of in situ cell
      kinetics. METHODS AND MATERIALS: SiHa (human squamous cell cervical tumor) cells
      were inoculated subcutaneously in the flank or back of SCID mice. When tumors
      reached a size of 200-300 mg, they received 25 Gy in 10 fractions over 5 days.
      Tumor regrowth and cell kinetics parameters were followed during treatment, and
      for 10 days after completion by measuring tumor volume and analyzing cellular
      BrdUrd and IdUrd incorporation with flow cytometry. RESULTS: Tumor volume was of
      limited use in assessing response to irradiation. The fraction of proliferating
      cells increased early during irradiation as did the labeling index; potential
      doubling time (Tpot) decreased during treatment and returned to the pre
      irradiation value after treatment. Cell cycle time remained relatively constant
      throughout the experiments. CONCLUSION: These results confirm the feasibility of
      evaluating cell cycle kinetics and repopulation parameters in a murine tumor
      model undergoing a fractionated course of irradiation. Repopulation of clonogenic
      tumor cells occurred more rapidly than predicted by pretreatment measurements,
      primarily due to an increased growth fraction and consequent decrease in Tpot.

PMID- 10078648
TI  - The effect of verapamil in the prevention of radiation-induced cataract.
AB  - PURPOSE: Cataract is an unavoidable complication when radiation therapy includes
      the lens, even in small doses. Alterations in the ion content of the lens were
      considered to play an essential role in cataract formation. In this experimental
      study, the effect of verapamil on ion concentrations within the irradiated lenses
      was investigated in rats. METHODS AND MATERIALS: Forty female Wistar albino rats,
      each weighing 180-250 g, were divided into three groups: (a) radiation treated (n
      = 10); (b) no treatment (n = 10); (c) or a combination of radiation and verapamil
      (n = 20). Both the radiation group and verapamil-treated group received 5 Gy
      radiation to the cranium in a single fraction, including the eyes, within the
      irradiation volume. All animals were sacrificed by bleeding, 7.5 weeks
      posttreatment. Calcium, sodium, and potassium levels were measured in blood and
      in lens homogenates. However, for technical reasons, magnesium levels could only
      be studied in lens homogenates. RESULTS: Potassium and sodium concentrations in
      lens homogenates did not differ in the control and radiation groups, but both
      were significantly lower in the verapamil-treated group (p = 0.001, p = 0.009,
      respectively). Calcium levels were higher in the radiation group and lower in the
      verapamil-treated group compared to the controls (p < 0.0001); magnesium levels
      did not differ (p = 0.37). CONCLUSION: Verapamil effectively decreased the lens
      calcium concentration, which is accepted as the key element in radiation
      cataractogenesis. It is therefore concluded that verapamil may reduce the risk of
      radiation-induced cataract formation.

PMID- 10078649
TI  - Magnetic resonance imaging of perfusion in rat cerebral 9L tumor after
      nicotinamide administration.
AB  - PURPOSE: To investigate the effect of nicotinamide on normal brain and 9L tumor
      blood flow in the rat using magnetic resonance imaging (MRI) and arterial spin
      tagging. METHODS AND MATERIALS: Using MRI at 7 Tesla, measurements of blood
      perfusion were determined from two-dimensional maps of intracerebral 9L rat
      tumors and normal Fischer rat brains. The spatial and temporal influence of
      nicotinamide, 500 mg/kg i.p., on cerebral blood flow (CBF) was studied in normal
      brain and tumors between 5 and 21 days after tumor implantation. The MRI CBF
      measurements employed a variable tip-angle-gradient-recalled echo (VTA-GRE-CBF)
      readout of the magnetization of the tissue slice. The VTA-GRE-CBF required 8
      minutes for a blood flow image with inplane resolution of 250 microm x 500 microm
      x 2 mm. RESULTS: Normal brain blood flow decreased following the administration
      of nicotinamide. In contrast, tumor blood flow remained unaffected in the time
      following nicotinamide administration. Consequently, the blood flowing in the
      tumor relative to that in normal brain demonstrated a significant and selective
      increase in response to nicotinamide administration. Relative tumor blood flow
      increased at 10 minutes after nicotinamide injection compared with predrug levels
      and remained elevated for at least 1 hour. CONCLUSION: The results suggest that
      nicotinamide will not enhance radiosensitivity of brain tumors. The results
      support the use of nicotinamide to improve delivery of anticancer therapeutics
      through its ability to selectively increase tumor blood flow relative to that in
      normal brain.

PMID- 10078650
TI  - Quantitative assessment of protein content in irradiated human skin.
AB  - PURPOSE: Radiation-induced fibrosis is a common late reaction of radiation
      therapy. Due to a lack of feasible noninvasive techniques to assess this
      reaction, the long-term development of radiation fibrosis is not well described.
      In order to develop quantitative means for the purpose, subcutaneous fibrosis of
      breast cancer patients after postmastectomy radiotherapy was evaluated by
      clinical scoring and a new technique based on dielectric properties of the skin.
      METHODS AND MATERIALS: Dielectric properties of biological tissues at
      radiofrequencies are principally determined by tissue water content. The major
      skin components are proteins, proteoglycans, and water either free or bound to
      the surface of proteins and proteoglycans. Since the MR studies have shown that
      bound water is tightly attached onto the surface of collagen, a dielectric
      measurement sensitive to bound water could be related to the protein content.
      Therefore, the dielectric constant of human skin was measured in vivo with an
      open-ended coaxial probe at electromagnetic (EM) frequencies in the range of
      delta-dispersion. Since the in vitro experiments with protein-water solutions
      have indicated that the slope of the dielectric constant vs. the EM frequency is
      a measure of the protein concentration, a respective slope was determined with
      irradiated skin of 14 breast cancer patients 2 years after postmastectomy
      radiotherapy at 63, 100, 300, and 500 MHz. Irradiated skin sites were clinically
      scored for subcutaneous fibrosis using a scale: none, slight, moderate, or severe
      fibrosis. RESULTS: A statistically significant correlation was found between the
      slope and the clinical score of subcutaneous fibrosis at 63, 100, and 300 MHz but
      not at 500 MHz. The correlation was best at 100 and 300 MHz. CONCLUSIONS:
      Considerable changes in the dielectric constant of the irradiated skin were
      found. The correlation between the dielectric constant and clinical score
      suggests that this novel technique is a potential tool for the follow-up and
      quantitative assessment of radiation-induced subcutaneous fibrosis.

PMID- 10078651
TI  - The assessment of RBE effects using the concept of biologically effective dose.
AB  - PURPOSE: To modify existing linear-quadratic (LQ) equations in order to take
      account of relative biological effectiveness (RBE) using the concept of
      biologically effective dose (BED). METHODS AND MATERIALS: Clinically useful forms
      of the LQ model have been modified to incorporate RBE effects in such a way as to
      allow comparison between high- and low-LET (linear energy transfer) radiations in
      terms of similar biological dose units. The new parameter in the formulation is
      RBEM, the intrinsic (or maximum) RBE at zero dose. The principal assumption
      (following Kellerer and Rossi; ref. 1) is that high-LET radiation modifies the
      alpha-coefficient of damage while leaving the beta-coefficient unaltered.
      RESULTS: The equations allow a quantitative estimation of how the apparent RBE
      will change with changes in dose/fraction or dose-rate and of how the magnitude
      and rate of change is governed by the low-LET alpha/beta ratio of the irradiated
      tissue. The modifications are applicable to all types of radiotherapy
      (fractionated, continuous low dose-rate, therapy with decaying sources, etc.). In
      cases where the normal tissue RBEM is greater than that for the tumor, the
      revised formulation helps explain why there will be situations where therapeutic
      index will be adversely affected by use of high-LET radiation. Such clinical
      advantages as have been observed are more likely to result from favorable
      geometrical sparing of critical normal tissues and/or the fact that slowly
      growing tumors may have alpha/beta values more typical of late-responding normal
      tissues. CONCLUSIONS: The incorporation of RBE into existing LQ methodology
      allows quantitative assessment of clinical applications of high-LET radiations
      via an examination of the associated BEDs. On the basis of such assessments high
      LET radiations are shown to confer few advantages.

PMID- 10078652
TI  - Automated treatment planning engine for prostate seed implant brachytherapy.
AB  - PURPOSE: To develop a computer-intelligent planning engine for automated
      treatment planning and optimization of ultrasound- and template-guided prostate
      seed implants. METHODS AND MATERIALS: The genetic algorithm was modified to
      reflect the 2D nature of the implantation template. A multi-objective decision
      scheme was used to rank competing solutions, taking into account dose uniformity
      and conformity to the planning target volume (PTV), dose-sparing of the urethra
      and the rectum, and the sensitivity of the resulting dosimetry to seed
      misplacement. Optimized treatment plans were evaluated using selected dosimetric
      quantifiers, dose-volume histogram (DVH), and sensitivity analysis based on
      simulated seed placement errors. These dosimetric planning components were
      integrated into the Prostate Implant Planning Engine for Radiotherapy (PIPER).
      RESULTS: PIPER has been used to produce a variety of plans for prostate seed
      implants. In general, maximization of the minimum peripheral dose (mPD) for given
      implanted total source strength tended to produce peripherally weighted seed
      patterns. Minimization of the urethral dose further reduced the loading in the
      central region of the PTV. Isodose conformity to the PTV was achieved when the
      set of objectives did not reflect seed positioning uncertainties; the
      corresponding optimal plan generally required fewer seeds and higher source
      strength per seed compared to the manual planning experience. When seed placement
      uncertainties were introduced into the set of treatment planning objectives, the
      optimal plan tended to reach a compromise between the preplanned outcome and the
      likelihood of retaining the preferred outcome after implantation. The reduction
      in the volatility of such seed configurations optimized under uncertainty was
      verified by sensitivity studies. CONCLUSION: An automated treatment planning
      engine incorporating real-time sensitivity analysis was found to be a useful tool
      in dosimetric planning for prostate brachytherapy.

PMID- 10078653
TI  - Comparison of calibration procedures for 192Ir high-dose-rate brachytherapy
      sources.
AB  - PURPOSE: To compare the efficacy of different calibration procedures for 192Ir
      high-dose-rate (HDR) brachytherapy sources and to determine their suitability in
      clinical practice. In addition the manufacturer's calibration is compared with
      our experimental measurements so that the accuracy of the source strength on the
      manufacturer certificate which is supplied with each new 192Ir source can be
      accessed. METHODS AND MATERIALS: We compared three types of calibration system:
      well-type chambers (HDR-1000 and SDS), cylindrical phantom, and plate phantom.
      The total number of measurements we obtained was 365. The number of sources used
      for the calibration procedure comparison was 20 and the number used for
      comparison with the manufacturer's calibration was 46. This study was made during
      the period 1989-1997. Also, Physikalisch-Technische Bundesanstalt (PTB)
      calibrated one of our sources using their PTB protocol so that the results could
      be compared with our own. RESULTS: The sensitivity of each system on scattering
      from the room walls was studied. It was found that different minimum lateral
      distances from the walls were required for the different systems tested: 15 cm
      and 25 cm for the well-type chambers, 75 cm for the cylindrical phantom, and 13
      cm for the plate phantom. The minimum thickness required to reach phantom
      scattering saturation for the plate phantom setup is 24 cm. The influence of the
      applicator material used in the calibration setup was found to be 1.7% for the
      stainless steel dosimetry applicator compared to the plastic 5F applicator. The
      accuracy of source positioning within the applicator can lead to dosimetric
      errors of +/-1.2% for the radial distance of 8.0 cm used with both solid
      phantoms. The change in the response for both well-type chambers was only 0.1%
      for changes in the source position within +/-7.5 mm around the response peak.
      Good agreement was found between all dosimetry systems included in our study.
      Taking the HDR-1000 well-type chamber results as a reference, we observed
      percentage root mean square (RMS) values of 0.11% for the SDS well-type chamber,
      0.44% for the cylindrical, and 0.60% for the plate phantom setup. A comparison of
      our results using the cylindrical phantom with those of the manufacturer showed a
      percentage RMS value of 3.3% with a percentage fractional error range of -13.0%
      to +6.0%. The comparison of our calibration results with those of PTB gave
      deviations less than 0.4% for all systems. CONCLUSIONS: Our results have shown
      that with careful use of all calibration system protocols an accurate
      determination of source strength can be obtained. However, the manufacturer's
      calibration is not accurate enough on its own, and it should be mandatory for
      clinics to always measure the source strength of newly delivered 192Ir
      brachytherapy sources. The influence of the applicator material, metal or
      plastic, should always be taken into account.

PMID- 10078654
TI  - A comparison of 3-D data correlation methods for fractionated stereotactic
      radiotherapy.
AB  - PURPOSE: Stereotactic radiosurgery is currently used to treat patients who are
      not good candidates for conventional neurosurgical procedures. For treatments of
      nonvascular tumor cells, it appears that fractionation offers a radiobiological
      advantage between tumor and normal tissues. Therefore, fractionated stereotactic
      radiotherapy (FSR) is preferred because it minimizes normal tissue complications
      and maximizes local tumor control probability. We have implemented a methodology
      clinically to perform the noninvasive patient repositioning technique. The 3-D
      data correlation method for high-precision and multiple fraction stereotactic
      treatments has been presented. METHODS AND MATERIALS: Three different
      optimization algorithms (Hooke and Jeeves optimization, simplex optimization, and
      simulated annealing optimization) are evaluated to calculate the transformation
      parameters necessary for FSR. A least-square object function is created to
      perform the 3-D data matching process. By minimizing the unconstrained object
      function value the best fit can be approached for the reference 3-D data sets.
      Simulation shows that these algorithms deliver results that are comparable to the
      previously published correlation algorithm (1,2) (singular value decomposition
      [SVD] method). The advantage for optimization algorithms is easily understood and
      can be readily implemented by using a personal computer (PC). The mathematical
      framework provides a tool to calculate the transformation matrix which can be
      used to adjust patient position for fractionated treatments. Therefore, using
      these algorithms for a high-precision fractionated treatment is possible without
      an invasive repeat fixation device and has been implemented clinically. A bite
      plate system was incorporated to acquire 3-D patient data. With a 3-D digital
      camera localization device, the patient motion can be followed in real time with
      the system calibrated to the isocenter. RESULTS: Two types of data sets are
      utilized to study the correlation results. One is using the digitized patient
      data which were retrieved clinically. The other is using the randomly generated
      data sets. Simulation errors for the optimization algorithms are all less than 1
      mm in translation and less than 1 degree in rotation. Currently, FSR is performed
      using special designed repeat fixation devices which assure reproducible patient
      position for multiple fractions of radiation treatment. Clinical results
      indicated that this technique provided excellent treatment results. CONCLUSION:
      Three optimization algorithms have been applied and evaluated in calculating the
      transformation parameters between two 3-D contours or digitized data points. The
      mathematical functions behind these optimization algorithms are straightforward
      and can be easily implemented. When incorporated with the proper CT/MR image data
      with an electronic portal imaging (EPI) system, this process can possibly verify
      the patient's treatment position whenever there is doubt about the movement
      during the treatment procedure.

PMID- 10078655
TI  - Minimizing static intensity modulation delivery time using an intensity solid
      paradigm.
AB  - PURPOSE: A leaf sequencing optimization algorithm that minimizes the delivery
      time for a static intensity modulated field is presented. METHODS AND MATERIALS:
      Sets of segments are created by intensity map operations subject to leaf
      collision constraints and tongue and groove effects. Each set's delivery time is
      evaluated as a function of leaf travel, beam on time, and the verify and record
      (V&R) overhead. The configuration with the minimum delivery time is chosen. As a
      test, optimization was done on three clinical cases of varying complexity.
      RESULTS: Assuming 10 x 10-cm fields with an average of 17 intensity levels, the
      optimization technique reduced delivery times by 27% and 45%, when compared to
      rod pushing and power of two extraction, respectively. The treatment time for the
      optimal case with a V&R overhead of 4 s would be 11.5 min for 9 coplanar ports.
      Tongue-and-groove underdosages are removed, and the worst case leakage is 2% of
      the peak dose. CONCLUSION: Compared to previously reported leaf sequencing
      methods, the new optimization algorithm described here reduces treatment times
      for complex static intensity modulated fields. Additionally, leakage is minimal
      and no tongue-and-groove underdosage occurs.

PMID- 10078656
TI  - Comparison of the clinical effectiveness of the 433 MHz Lucite cone applicator
      with that of a conventional waveguide applicator in applications of superficial
      hyperthermia.
AB  - PURPOSE: This report presents the final stage of our program to improve the
      quality of our superficial hyperthermia treatments. We have already demonstrated
      that the Lucite cone applicator (LCA), our technically improved water-filled,
      wave-guide applicator (WGA), is superior to the conventional WGA. The main
      objective of the present study was to investigate whether the technical
      improvements of a WGA were reflected in an improved clinical performance, e.g., a
      better temperature distribution. METHODS AND MATERIALS: Power and temperature
      analyses were performed retrospectively on 128 treatments of superficially
      located tumors (less than 4 cm depth). Twenty-three patients were treated
      alternately with a WGA setup and a LCA setup. RESULTS: The average power level
      per antenna in an array was 48 W and 62 W for the WGA and LCA respectively. The
      average invasively measured temperatures increased by 0.27 degrees C when the
      LCAs were used. The temperature difference between the center and the periphery
      of an antenna, averaged over the complete array of antennae, was 0.43 degrees C
      using WGAs and -0.05 degrees C using LCAs indicating a more uniform heating. The
      T90 of the invasively measured temperatures remained unchanged (WGA: 39.4 degrees
      C versus LCA: 39.5 degrees C). CONCLUSION: The LCA is now our standard applicator
      for superficial hyperthermia treatments as it is technically and clinically
      proven to be superior to the WGA.

PMID- 10078657
TI  - Physics of rotating gamma systems for stereotactic radiosurgery.
AB  - PURPOSE: The purpose of this study was to evaluate the characteristics of a new
      rotating gamma system for stereotactic radiosurgery by comparison with a well
      accepted system. METHODS AND MATERIALS: A novel gamma unit for stereotactic
      radiosurgery has been developed and distributed to 15 hospitals in China. The
      unit contains 30 cobalt-60 gamma radiation sources with initial activity of 200
      Ci (7.4 x 10(12) Bq) each. The sources are positioned along 30 arcs, and rotate
      continuously as a group in an axis orthogonal to the patient's body. Measurements
      have been made on a representative unit installed in the Auhai Radiosurgery
      Center at the Beijing Navy General Hospital in the People's Republic of China.
      Ionization chambers calibrated by an American accredited dosimetry calibration
      laboratory were used for these measurements, as well as radiochromic film and
      thermoluminescent dosimeters. The unit tested utilizes collimators of nominal
      diameters of 4, 8, 14, and 18 mm. Radiochromic film samples from a Leksell Model
      U Gamma Knife were evaluated by the same laboratory and are presented for
      comparison. The treatment planning system was not evaluated. RESULTS: Radiation
      absorbed dose rates and profiles measured for this unit are comparable to those
      previously measured with the same techniques for the Leksell Model U Gamma Knife
      units in San Diego and Atlanta. CONCLUSION: This unit is capable of producing
      well collimated beams of high energy photons, suitable for stereotactic
      radiosurgery. It has similar physical characteristics to those previously
      reported for the Leksell Model U Gamma Knife unit.

PMID- 10078658
TI  - A more robust biologically based ranking criterion for treatment plans.

PMID- 10078659
TI  - Is it possible to optimize a radiotherapy treatment plan?

PMID- 10078660
TI  - PSA relapse definitions--the Vancouver Rules show superior predictive power.

PMID- 10078661
TI  - How carefully can we phenotype patients suspected of malignant hyperthermia
      susceptibility?

PMID- 10078662
TI  - Memory function during anesthesia.

PMID- 10078663
TI  - Is gaining control of the autonomic nervous system important to our specialty?

PMID- 10078664
TI  - Comparison of European and North American malignant hyperthermia diagnostic
      protocol outcomes for use in genetic studies.
AB  - BACKGROUND: Halothane and caffeine diagnostic protocols and an experimental
      ryanodine test from the North American Malignant Hyperthermia (MH) Group (NAMHG)
      and the European MH Group (EMHG) have not been compared in the same persons until
      now. METHODS: The outcomes of the NAMHG and EMHG halothane and caffeine
      contracture tests were compared in 84 persons referred for diagnostic testing. In
      addition, the authors assessed the experimental ryanodine protocol in 50 of these
      persons. RESULTS: Although the NAMHG and EMHG halothane protocols are slightly
      different methodologically, each yielded outcomes in close (84-100%) agreement
      with diagnoses made by the other protocol. Excluding 23 persons judged to be
      equivocal (marginally positive responders) by the EMHG protocol resulted in fewer
      persons classified as normal and MH susceptible (42 and 19, respectively) than
      those classified by the NAMHG protocol (48 and 34, respectively). For the 61
      persons not excluded as equivocal, the diagnoses were identical by both
      protocols, with the exception of one person who was diagnosed as MH susceptible
      by the NAMHG protocol and as "normal" by the EMHG protocol. The NAMHG protocol
      produced only two equivocal diagnoses. Therefore, a normal or MH diagnosis by the
      NAMHG protocol was frequently associated with an equivocal diagnosis by the EMHG
      protocol. The time to 0.2-g contracture after the addition of 1 microM ryanodine
      completely separated populations, which was in agreement with the EMHG protocol
      and, except for one person, with the NAMHG protocol. CONCLUSIONS: Overall, the
      NAMHG and EMHG protocols and the experimental ryanodine test yielded similar
      diagnoses. The EMHG protocol reduced the number of marginal responders in the
      final analysis, which may make the remaining diagnoses slightly more accurate for
      use in genetic studies.

PMID- 10078665
TI  - Increased reading speed for stories presented during general anesthesia.
AB  - BACKGROUND: In the absence of explicit memories such as the recall and
      recognition of intraoperative events, memory of auditory information played
      during general anesthesia has been demonstrated with several tests of implicit
      memory. In contrast to explicit memory, which requires conscious recollection,
      implicit memory does not require recollection of previous experiences and is
      evidenced by a priming effect on task performance. The authors evaluated the
      effect of a standardized anesthetic technique on implicit memory, first using a
      word stem completion task, and then a reading speed task in a subsequent study.
      METHODS: While undergoing lumbar disc surgery, 60 patients were exposed to
      auditory materials via headphones in two successive experiments. A balanced
      intravenous technique with propofol and alfentanil infusions and a nitrous oxide
      oxygen mixture was used to maintain adequate anesthesia. In the first experiment,
      30 patients were exposed randomly to one of the two lists of 34 repeated German
      nouns; in the second experiment, 30 patients were exposed to one of two tapes
      containing two short stories. Thirty control patients for each experiment heard
      the tapes without receiving anesthesia. All patients were tested for implicit
      memory 6-8 h later: A word stem completion task for the words and a reading speed
      task for the stories were used as measures of implicit memory. RESULTS: The
      control group completed the word stems significantly more often with the words
      that they had heard previously, but no such effect was found in the anesthetized
      group. However, both the control and patient groups showed a decreased reading
      time of about 40 ms per word for the previously presented stories compared with
      the new stories. The patients had no explicit memory of intraoperative events.
      CONCLUSIONS: Implicit memory was demonstrated after anesthesia by the reading
      speed task but not by the word stem completion task. Some methodologic aspects,
      such as using low frequency words or varying study and test modalities, may
      account for the negative results of the word stem completion task. Another
      explanation is that anesthesia with propofol, alfentanil, and nitrous oxide
      suppressed the word priming but not the reading speed measure of implicit memory.
      The reading speed paradigm seems to provide a stable and reliable measurement of
      implicit memory.

PMID- 10078666
TI  - Dependence of explicit and implicit memory on hypnotic state in trauma patients.
AB  - BACKGROUND: It is still unclear whether memory of intraoperative events results
      entirely from moments of inadequate anesthesia. The current study was designed to
      determine whether the probability of memory declines with increasing depth of the
      hypnotic state. METHOD: A list of words was played via headphones during surgery
      to patients who had suffered acute trauma. Several commonly used indicators of
      anesthetic effect, including the bispectral index, were recorded during word
      presentation. First, these indicators served as predictors of the memory
      performance in a postoperative word stem completion test. Second, general memory
      performance observed in the first part was separated into explicit and implicit
      memory using the process dissociation procedure, and then two models of memory
      were compared: One model assumed that the probability of explicit and implicit
      memory decreases with increasing depth of hypnotic state (individual differences
      model), whereas the other assumed equal memory performance for all patients
      regardless of their level of hypnotic state. RESULTS: General memory performance
      declined with decreasing bispectral index values. None of the other indicators of
      hypnotic state were related to general memory performance. Memory was still
      significant at bispectral index levels between 60 and 40. A comparison of the two
      models of memory resulted in a better fit of the individual differences model,
      thus providing evidence of a dependence of explicit and implicit memory on the
      hypnotic state. Quantification of explicit and implicit memory revealed a
      significant implicit but no reliable explicit memory performance. CONCLUSIONS:
      This study clearly indicates that memory is related to the depth of hypnosis. The
      observed memory performance should be interpreted in terms of implicit memory.
      Auditory information processing occurred at bispectral index levels between 60
      and 40.

PMID- 10078667
TI  - Cardiac baroreflex during the postoperative period in patients with hypertension:
      effect of clonidine.
AB  - BACKGROUND: Patients with essential hypertension show altered baroreflex control
      of heart rate, and during the perioperative period they demonstrate increased
      circulatory instability. Clonidine has been shown to reduce perioperative
      circulatory instability. This study documents changes in measures of heart rate
      control after surgery in patients with essential hypertension and determines the
      effects of clonidine on postoperative heart rate control in these patients.
      METHODS: Using a randomized double-blind placebo-controlled design, 20 patients
      with essential hypertension (systolic pressure >160 mm Hg or diastolic pressure
      >95 mm Hg for > or =1 yr) were assigned to receive clonidine (or placebo), 6
      microg/kg orally 120 min before anesthesia and 3 microg/kg intravenously over 60
      min before the end of surgery. The spontaneous baroreflex ("sequence") technique
      and analysis of heart rate variability were used to quantify control of heart
      rate at baseline, before induction of anesthesia, and 1 and 3 h postoperatively.
      RESULTS: Baroreflex slope and heart rate variability were reduced postoperatively
      in patients given placebo but not those given clonidine. Clonidine resulted in
      greater postoperative baroreflex slope and power at all frequency ranges compared
      with placebo (4.9+/-2.9 vs. 2.2+/-2.1 ms/mm Hg for baroreflex slope, 354+/-685
      vs. 30+/-37 ms2/Hz for high frequency variability). Clonidine also resulted in
      lower concentrations of catecholamine, decreased mean heart rate and blood
      pressure, and decreased perioperative tachycardia and hypertension. CONCLUSIONS:
      Patients with hypertension exhibit reduced heart rate control during the recovery
      period after elective surgery. Clonidine prevents this reduction in heart rate
      control. This may represent a basis for the improved circulatory stability seen
      with perioperative administration of clonidine.

PMID- 10078668
TI  - Causes of nitrous oxide contamination in operating rooms.
AB  - BACKGROUND: To reduce the ambient concentration of waste anesthetic agents,
      exhaust gas scavenging systems are standard in almost all operating rooms. The
      incidence of contamination and the factors that may increase the concentrations
      of ambient anesthetic gases have not been evaluated fully during routine
      circumstances, however. METHODS: Concentrations of nitrous oxide (N2O) in ambient
      air were monitored automatically in 10 operating rooms in Kagoshima University
      Hospital from January to March 1997. Ambient air was sampled automatically from
      each operating room, and the concentrations of N2O were analyzed every 22 min by
      an infrared spectrophotometer. The output of the N2O analyzer was integrated
      electronically regarding time, and data were displayed on a monitor in the
      administrative office for anesthesia supervisors. A concentration of N2O > 50
      parts per million was regarded as abnormally high and was displayed with an alarm
      signal. The cause of the high concentration of N2O was then sought. RESULTS:
      During the 3-month investigation, N2O was used in 402 cases. Abnormally high
      concentrations of N2O were detected at some time during 104 (25.9%) of those
      cases. The causes were mask ventilation (42 cases, 40.4% of detected cases),
      unconnected scavenging systems (20 cases, 19.2%), leak around uncuffed pediatric
      endotracheal tube (13 cases, 12.5%), equipment leakage (12 cases, 11.5%), and
      others (17 cases, 16.4%). CONCLUSIONS: N2O contamination was common during
      routine circumstances in our operating rooms. An unconnected scavenging system
      led to the highest concentrations of N2O recorded. Proper use of scavenging
      systems is necessary if contamination by anesthetic gas is to be limited.

PMID- 10078669
TI  - Effects of anticholinergics on postoperative vomiting, recovery, and hospital
      stay in children undergoing tonsillectomy with or without adenoidectomy.
AB  - BACKGROUND: Nausea and vomiting are the most frequent problems after minor
      ambulatory surgical procedures. The agents used to induce and maintain anesthesia
      may modify the incidence of emesis. When neuromuscular blockade is antagonized
      with anticholinesterases, atropine or glycopyrrolate is used commonly to prevent
      bradycardia and excessive oral secretions. This study was designed to evaluate
      the effect of atropine and glycopyrrolate on postoperative vomiting in children.
      METHODS: Ninety-three patients undergoing tonsillectomy with or without
      adenoidectomy were studied. After inhalation induction of anesthesia with nitrous
      oxide, oxygen, and halothane, anesthesia was maintained with a nitrous oxide
      oxygen mixture, halothane, morphine, and atracurium. Patients were randomized to
      receive, in a double-blinded manner, either 15 microg/kg atropine or 10 microg/kg
      glycopyrrolate with 60 microg/kg neostigmine to reverse neuromuscular blockade.
      Patient recovery, the incidence of postoperative emesis, antiemetic therapy, and
      the duration of postoperative hospital stay were assessed. RESULTS: There were no
      significant differences in age, gender, weight, or discharge time from the
      postanesthesia care unit or the hospital between the groups. Twenty-four hours
      after operation, the incidence of vomiting in the atropine group (56%) was
      significantly less than in the glycopyrrolate group (81%; P<0.05). There was no
      significant difference between the atropine and glycopyrrolate groups in the
      number of patients who required antiemetics or additional analgesics.
      CONCLUSIONS: In children undergoing tonsillectomy with or without adenoidectomy,
      reversal of neuromuscular blockade with atropine and neostigmine is associated
      with a lesser incidence of postoperative emesis compared with glycopyrrolate and
      neostigmine.

PMID- 10078670
TI  - Functional brain imaging during anesthesia in humans: effects of halothane on
      global and regional cerebral glucose metabolism.
AB  - BACKGROUND: Propofol and isoflurane anesthesia were studied previously with
      functional brain imaging in humans to begin identifying key brain areas involved
      with mediating anesthetic-induced unconsciousness. The authors describe an
      additional positron emission tomography study of halothane's in vivo cerebral
      metabolic effects. METHODS: Five male volunteers each underwent two positron
      emission tomography scans. One scan assessed awake-baseline metabolism, and the
      other scan assessed metabolism during halothane anesthesia titrated to the point
      of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained
      using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of
      interest were analyzed for changes in both absolute and relative glucose
      metabolism. In addition, relative changes in metabolism were evaluated using
      statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged
      6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism
      40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism
      did not increase in any brain areas for any volunteer. The statistical parametric
      mapping analysis revealed significantly less relative metabolism in the basal
      forebrain, thalamus, limbic system, cerebellum, and occiput during halothane
      anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic
      reduction with significant shifts in regional metabolism. Comparisons with
      previous studies reveal similar absolute and relative metabolic effects for
      halothane and isoflurane. Propofol, however, was associated with larger absolute
      metabolic reductions, suppression of relative cortical metabolism more than
      either inhalational agent, and significantly less suppression of relative basal
      ganglia and midbrain metabolism.

PMID- 10078671
TI  - Dose-response effects of spinal neostigmine added to bupivacaine spinal
      anesthesia in volunteers.
AB  - BACKGROUND: Intrathecal adjuncts often are used to enhance small-dose spinal
      bupivacaine for ambulatory anesthesia. Neostigmine is a novel spinal analgesic
      that could be a useful adjunct, but no data exist to assess the effects of
      neostigmine on small-dose bupivacaine spinal anesthesia. METHODS: Eighteen
      volunteers received two bupivacaine spinal anesthetics (7.5 mg) in a randomized,
      double-blinded, crossover design. Dextrose, 5% (1 ml), was added to one spinal
      infusion and 6.25, 12.5, or 50 microg neostigmine in dextrose, 5%, was added to
      the other spinal. Sensory block was assessed with pinprick; by the duration of
      tolerance to electric stimulation equivalent to surgical incision at the pubis,
      knee, and ankle; and by the duration of tolerance to thigh tourniquet. Motor
      block at the quadriceps was assessed with surface electromyography. Side effects
      (nausea, vomiting, pruritus, and sedation) were noted. Hemodynamic and
      respiratory parameters were recorded every 5 min. Dose-response relations were
      assessed with analysis of variance, paired t tests, or Spearman rank correlation.
      RESULTS: The addition of 50 microg neostigmine significantly increased the
      duration of sensory and motor block and the time until discharge criteria were
      achieved. The addition of neostigmine produced dose-dependent nausea (33-67%) and
      vomiting (17-50%). Neostigmine at these doses had no effect on hemodynamic or
      respiratory parameters. CONCLUSIONS: The addition of 50 microg neostigmine
      prolonged the duration of sensory and motor block. However, high incidences of
      side effects and delayed recovery from anesthesia with the addition of 6.25 to 50
      microg neostigmine may limit the clinical use of these doses for outpatient
      spinal anesthesia.

PMID- 10078672
TI  - Behavioral and physiological effects of remifentanil and alfentanil in healthy
      volunteers.
AB  - BACKGROUND: The subjective and psychomotor effects of remifentanil have not been
      evaluated. Accordingly, the authors used mood inventories and psychomotor tests
      to characterize the effects of remifentanil in healthy, non-drug-abusing
      volunteers. Alfentanil was used as a comparator drug. METHODS: Ten healthy
      volunteers were enrolled in a randomized, double-blinded, placebo-controlled,
      crossover trial in which they received an infusion of saline, remifentanil, or
      alfentanil for 120 min. The age- and weight-adjusted infusions (determined with
      STANPUMP, a computer modeling software package) were given to achieve three
      predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and
      3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests
      were completed, and miosis was assessed, during and after the infusions. In
      addition, analgesia was tested at each dose level using a cold-pressor test.
      RESULTS: Remifentanil had prototypic micro-like opioid subjective effects,
      impaired psychomotor performance, and produced analgesia. Alfentanil at the dose
      range tested had more mild effects on these measures, and the analgesia data
      indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may
      exist between remifentanil and alfentanil. A psychomotor test administered 60 min
      after the remifentanil infusion was discontinued showed that the volunteers were
      still impaired, although they reported feeling no drug effects. CONCLUSIONS: The
      notion that the pharmacodynamic effects of remifentanil are extremely short-lived
      after the drug is no longer administered must be questioned given our findings
      that psychomotor effects were still apparent 1 h after the infusion was
      discontinued.

PMID- 10078673
TI  - Comparison of three solutions of ropivacaine/fentanyl for postoperative patient
      controlled epidural analgesia.
AB  - BACKGROUND: Ropivacaine, 0.2%, is a new local anesthetic approved for epidural
      analgesia. The addition of 4 microg/ml fentanyl improves analgesia from epidural
      ropivacaine. Use of a lower concentration of ropivacaine-fentanyl may further
      improve analgesia or decrease side effects. METHODS: Thirty patients undergoing
      lower abdominal surgery were randomized in a double-blinded manner to receive one
      of three solutions: 0.2% ropivacaine-4 microg fentanyl 0.1% ropivacaine-2 microg
      fentanyl, or 0.05% ropivacaine-1 microg fentanyl for patient-controlled epidural
      analgesia after standardized combined epidural and general anesthesia. Patient
      controlled epidural analgesia settings and adjustments for the three solutions
      were standardized to deliver equivalent drug doses. Pain scores (rest, cough, and
      ambulation), side effects (nausea, pruritus, sedation, motor block, hypotension,
      and orthostasis), and patient-controlled epidural analgesia consumption were
      measured for 48 h. RESULTS: All three solutions produced equivalent analgesia.
      Motor block was significantly more common (30 vs. 0%) and more intense with the
      0.2% ropivacaine-4 microg fentanyl solution. Other side effects were equivalent
      between solutions and mild in severity. A significantly smaller volume of 0.2%
      ropivacaine-4 microg fentanyl solution was used, whereas the 0.1% ropivacaine-2
      microg fentanyl group used a significantly greater amount of ropivacaine and
      fentanyl. CONCLUSIONS: Lesser concentrations of ropivacaine and fentanyl provide
      comparable analgesia with less motor block despite the use of similar amounts of
      ropivacaine and fentanyl. This finding suggests that concentration of local
      anesthetic solution at low doses is a primary determinant of motor block with
      patient-controlled epidural analgesia after lower abdominal surgery.

PMID- 10078674
TI  - Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia
      following orthopedic surgery.
AB  - BACKGROUND: Sufentanil is a potent but short-acting spinal analgesic used to
      manage perioperative pain. This study evaluated the influence of transdermal
      nitroglycerine on the analgesic action of spinal sufentanil in patients
      undergoing orthopedic surgery. METHODS: Fifty-six patients were randomized to one
      of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous
      midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally
      (saline or 10 microg sufentanil). Twenty to 30 min after the spinal puncture, a
      transdermal patch of either 5 mg nitroglycerin or placebo was applied. The
      control group received spinal saline and transdermal placebo. The sufentanil
      group received spinal sufentanil and transdermal placebo. The nitroglycerin group
      received spinal saline and transdermal nitroglycerine patch. Finally, the
      sufentanil-nitroglycerin group received spinal sufentanil and transdermal
      nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual
      analog scale. RESULTS: The time to first rescue analgesic medication was longer
      for the sufentanil-nitroglycerin group (785+/-483 min) compared with the other
      groups (P<0.005). The time to first rescue analgesics was also longer for the
      sufentanil group compared with the control group (P<0.05). The sufentanil
      nitroglycerin group group required less rescue analgesics in 24 h compared with
      the other groups (P<0.02) and had lesser 24-h pain visual analog scale scores
      compared with the control group (P<0.005), although these scores were similar to
      the sufentanil and nitroglycerin groups (P>0.05). The incidence of perioperative
      adverse effects was similar among groups (P>0.05). CONCLUSIONS: Transdermal
      nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in
      postoperative analgesia itself, but it prolonged the analgesic effect of spinal
      sufentanil (10 microg) and provided 13 h of effective postoperative analgesia
      after knee surgery.

PMID- 10078675
TI  - Benzodiazepine premedication: can it improve outcome in patients undergoing
      breast biopsy procedures?
AB  - BACKGROUND: Women awaiting needle-guided breast biopsy procedures may experience
      high anxiety levels. A randomized, double-blind, placebo-controlled study was
      designed to evaluate the ability of midazolam and diazepam (in a lipid emulsion
      [Dizac]) to improve patient comfort during needle localization and breast biopsy
      procedures. METHODS: Ninety women received two consecutive doses of a study
      medication, one before the mammographic needle localization and a second before
      entering the operating room. Patients were assigned randomly to receive saline,
      2.0 ml intravenously, at the two time points; midazolam, 1.0 mg intravenously and
      2.0 mg intravenously; or diazepam emulsion, 2.0 mg intravenously and 5.0 mg
      intravenously, respectively. Patients assessed their anxiety levels before the
      needle localization, before entering the operating room, and on arrival in the
      operating room. Patients completed a questionnaire evaluating their perioperative
      experience at the time of discharge. RESULTS: Patient satisfaction during needle
      localization was significantly improved in both benzodiazepine treatment groups
      (vs. saline). The incidence of moderate-to-severe discomfort during needle
      localization was lower in the midazolam (20%) and diazepam emulsion (6%) groups
      compared with the saline group (70%) (P<0.05). The preoperative visual analogue
      scale anxiety scores were similar in all three groups. In the operating room,
      however, anxiety scores were 55% and 68% lower after midazolam (21+/-19) and
      diazepam emulsion (15+/-14) compared with saline (46+/-28). Finally, there was no
      difference in the time to achieve home-readiness or actual discharge time among
      the three groups. CONCLUSIONS: Premedication with midazolam or diazepam emulsion
      improved patients' comfort during needle localization procedures and
      significantly reduced intraoperative anxiety levels before breast biopsy
      procedures without prolonging discharge times. Use of diazepam emulsion may be an
      effective alternative to midazolam in this population.

PMID- 10078676
TI  - Contraction-relaxation coupling and impaired left ventricular performance in
      coronary surgery patients.
AB  - BACKGROUND: Dependence of left ventricular (LV) relaxation on cardiac systolic
      load is a function of myocardial contractility. The authors hypothesized that, if
      a tight coupling would exist between LV contraction and relaxation, the changes
      in relaxation rate with an increase in cardiac systolic load would be related to
      the changes in LV contraction. METHODS: Coronary surgery patients (n = 120) with
      preoperative ejection fraction >40% were included. High-fidelity LV pressure
      tracings (n = 120) and transgastric transesophageal echocardiographic data (n =
      40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on
      contraction were evaluated by analysis of changes in dP/dt(max) and stroke area.
      Effects on relaxation were assessed by analysis of R (slope of the relation
      between tau and end-systolic pressure). Correlations were calculated with linear
      regression analysis using Pearson's coefficient r. RESULTS: Baseline LV end
      diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic
      LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was
      variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed
      with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in
      dP/dt(max) and in stroke area were closely related to individual R values (r =
      0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes
      in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001,
      respectively). CONCLUSIONS: A tight coupling was observed between contraction and
      relaxation. Leg raising identified patients who developed a load-dependent
      impairment of LV performance and increased load dependence of LV relaxation.

PMID- 10078677
TI  - Postoperative behavioral outcomes in children: effects of sedative premedication.
AB  - BACKGROUND: Although multiple studies document the effect of sedative
      premedication on preoperative anxiety in children, there is a paucity of data
      regarding its effect on postoperative behavioral outcomes. METHODS: After
      screening for recent stressful life events, children undergoing anesthesia and
      surgery were assigned randomly to receive either 0.5 mg/kg midazolam in 15 mg/kg
      acetaminophen orally (n = 43) or 15 mg/kg acetaminophen orally (n = 43). Using
      validated measures of anxiety, children were evaluated before and after
      administration of the intervention and during induction of anesthesia. On
      postoperative days 1, 2, 3, 7, and 14, the behavioral recovery of the children
      was assessed using the Post Hospitalization Behavior Questionnaire. RESULTS: The
      intervention group demonstrated significantly lower anxiety levels compared with
      the placebo group on separation to the operating room and during induction of
      anesthesia (F[1,77] = 3.95, P = 0.041). Using a multivariate logistic regression
      model, the authors found that the presence or absence of postoperative behavioral
      changes was dependent on the group assignment (R = 0.18, P = 0.0001) and days
      after operation (R = -0.20, P = 0.0001). Post hoc analysis demonstrated that
      during postoperative days 1-7, a significantly smaller number of children in the
      midazolam group manifested negative behavioral changes. At week 2
      postoperatively, however, there were no significant differences between the
      midazolam and placebo groups. CONCLUSIONS: Children who are premedicated with
      midazolam before surgery have fewer negative behavioral changes during the first
      postoperative week.

PMID- 10078678
TI  - Clinical isoflurane metabolism by cytochrome P450 2E1.
AB  - BACKGROUND: Some evidence suggests that isoflurane metabolism to trifluoroacetic
      acid and inorganic fluoride by human liver microsomes in vitro is catalyzed by
      cytochrome P450 2E1 (CYP2E1). This investigation tested the hypothesis that P450
      2E1 predominantly catalyzes human isoflurane metabolism in vivo. Disulfiram,
      which is converted in vivo to a selective inhibitor of P450 2E1, was used as a
      metabolic probe for P450 2E1. METHODS: Twenty-two elective surgery patients who
      provided institutionally-approved written informed consent were randomized to
      receive disulfiram (500 mg orally, N = 12) or nothing (controls, N = 10) the
      evening before surgery. All patients received a standard isoflurane anesthetic
      (1.5% end-tidal in oxygen) for 8 hr. Urine and plasma trifluoroacetic acid and
      fluoride concentrations were quantitated in samples obtained for 4 days
      postoperatively. RESULTS: Patient groups were similar with respect to age,
      weight, gender, duration of surgery, blood loss, and delivered isoflurane dose,
      measured by cumulative end-tidal isoflurane concentrations (9.7-10.2 MAC-hr).
      Postoperative urine excretion of trifluoroacetic acid (days 1-4) and fluoride
      (days 1-3) was significantly (P<0.05) diminished in disulfiram-treated patients.
      Cumulative 0-96 hr excretion of trifluoroacetic acid and fluoride in disulfiram
      treated patients was 34+/-72 and 270+/-70 micromoles (mean +/- SD), respectively,
      compared to 440+/-360 and 1500+/-800 micromoles in controls (P<0.05 for both).
      Disulfiram also abolished the rise in plasma metabolite concentrations.
      CONCLUSIONS: Disulfiram, a selective inhibitor of human hepatic P450 2E1,
      prevented 80-90% of isoflurane metabolism. These results suggest that P450 2E1 is
      the predominant P450 isoform responsible for human clinical isoflurane metabolism
      in vivo.

PMID- 10078679
TI  - A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125%
      bupivacaine with sufentanil for epidural labor analgesia.
AB  - BACKGROUND: This study intends to evaluate the benefits of the administration of
      intermittent bolus doses of ropivacaine (0.125%) compared with bupivacaine
      (0.125%) after addition of sufentanil for analgesia during labor. METHODS: One
      hundred thirty American Society of Anesthesiologists physical status 1 or 2
      parturients were studied. The 90 initial patients were assigned randomly to
      receive 10 ml bupivacaine, 0.125%, plus 7.5 microg sufentanil (initial
      bupivacaine 0.125% group) or ropivacaine, 0.125%, plus 7.5 microg sufentanil
      (ropivacaine 0.125% group). Forty additional patients were recruited and received
      0.125% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.125%
      group) or 0.100% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine
      0.100% group). The duration of analgesia, visual analogue scores for pain, motor
      blockade (using a six-point modified Bromage scale), patient satisfaction scores,
      nausea, pruritus, heart rate, and blood pressure were recorded. RESULTS:
      Bupivacaine 0.125% and ropivacaine 0.125% coadministered with sufentanil provided
      rapid and complete analgesia. Onset of analgesia occurred after +/-15 min and
      lasted +/-90 min. After the third epidural injection, patients in the ropivacaine
      group experienced significantly less severe motor blockade than patients in the
      initial bupivacaine 0.125% group. At this point, 93% of the patients in the
      ropivacaine group were free from motor impairment versus 66% in the bupivacaine
      group (P<0.05). Comparable levels of motor blockade were obtained in both
      additional groups. Patients' evaluation of their analgesia was worst in the
      bupivacaine 0.100% group. CONCLUSIONS: Ropivacaine 0.125% with sufentanil affords
      reliable analgesia with minimal motor blockade.

PMID- 10078680
TI  - Potassium channel-mediated hyperpolarization of mesenteric vascular smooth muscle
      by isoflurane.
AB  - BACKGROUND: A primary source of calcium (Ca2+) necessary for excitation
      contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+
      channels. Thus, force generation in VSM is coupled closely to resting
      transmembrane potential, which itself is primarily a function of potassium
      conductance. Previously, the authors reported that volatile anesthetics
      hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins.
      The current study was designed to determine whether isoflurane-mediated
      hyperpolarization is the result of specific effects on one or more of four types
      of potassium channels known to exist in VSM. METHODS: Transmembrane potentials
      (Em) were recorded from in situ mesenteric capacitance and resistance vessels in
      Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective
      inhibitors of each of four types of potassium channels known to exist in VSM were
      administered in the superfusate of the vessel preparations to assess their
      effects on isoflurane-mediated hyperpolarization. RESULTS: Resting VSM Em ranged
      from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a
      significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel
      inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin
      (inhibitor of high conductance calcium-activated potassium channels) and 1 microM
      glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium
      channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum
      alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which
      was not significant). In contrast, isoflurane hyperpolarized the VSM
      significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage
      dependent potassium channels) or 10 microM barium chloride (an inhibitor of
      inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em). CONCLUSIONS:
      These results suggest that isoflurane-mediated hyperpolarization (and associated
      relaxation) of VSM can be attributed in part to an enhanced (or maintained)
      opening of calcium-activated and adenosine triphosphate-sensitive potassium
      channels but not voltage-dependent or inward rectifier potassium channels.

PMID- 10078681
TI  - The effect of graded postischemic spinal cord hypothermia on neurological outcome
      and histopathology after transient spinal ischemia in rat.
AB  - BACKGROUND: Previous data have shown that postischemic brain hypothermia is
      protective. The authors evaluated the effect of postischemic spinal hypothermia
      on neurologic function and spinal histopathologic indices after aortic occlusion
      in the rat. METHODS: Spinal ischemia was induced by aortic occlusion lasting 10
      min. After ischemia, spinal hypothermia was induced using a subcutaneous heat
      exchanger. Three studies were conducted. In the first study, the intrathecal
      temperature was decreased to 34, 30, or 27 degrees C for 2 h beginning with
      initial reperfusion. In the second study, hypothermia (target intrathecal
      temperature 27 degrees C) was initiated with reflow and maintained for 15 or 120
      min. In the third study, the intrathecal temperature was decreased to 27 degrees
      C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals
      survived for 2 or 3 days, at which time they were examined and perfusion fixed
      with 4% paraformaldehyde. RESULTS: Normothermic ischemia followed by normothermic
      reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate
      postischemic hypothermia (27 degrees C for 2 h) resulted in decreasing motor
      dysfunction. Incomplete protection was noted at 34 degrees C. Fifteen minutes of
      immediate cooling (27 degrees C) also provided significant protection. Delay of
      onset of post-reflow hypothermia (27 degrees C) by 5 min or more failed to
      provide protection. Histopathologic analysis revealed temperature-dependent
      suppression of spinal neurodegeneration, with no effect of delayed cooling.
      CONCLUSIONS: These findings indicate that the immediate period of reperfusion (0
      15 min) represents a critical period that ultimately defines the degree of spinal
      neuronal degeneration. Hypothermia, when initiated during this period, showed
      significant protection, with the highest efficacy observed at 27 degrees C.

PMID- 10078682
TI  - Effects of isoflurane anesthesia on pulmonary vascular response to K+ ATP channel
      activation and circulatory hypotension in chronically instrumented dogs.
AB  - BACKGROUND: The objective of this study was to evaluate the effects of isoflurane
      anesthesia on the pulmonary vascular responses to exogenous adenosine
      triphosphate-sensitive potassium (K+ ATP) channel activation and circulatory
      hypotension compared with responses measured in the conscious state. In addition,
      the extent to which K+ ATP channel inhibition modulates the pulmonary vascular
      response to circulatory hypotension in conscious and isoflurane-anesthetized dogs
      was assessed. METHODS: Fifteen conditioned, male mongrel dogs were fitted with
      instruments for long-term monitoring to measure the left pulmonary vascular
      pressure-flow relation. The dose-response relation to the K+ ATP channel agonist,
      lemakalim, and the pulmonary vascular response to circulatory hypotension were
      assessed in conscious and isoflurane-anesthetized (approximately 1.2 minimum
      alveolar concentration) dogs. The effect of the selective K+ ATP channel
      antagonist, glibenclamide, on the pulmonary vascular response to hypotension was
      also assessed in conscious and isoflurane-anesthetized dogs. RESULTS: Isoflurane
      had no effect on the baseline pulmonary circulation, but it attenuated (P<0.05)
      the pulmonary vasodilator response to lemakalim. Reducing the mean systemic
      arterial pressure to approximately 50 mm Hg resulted in pulmonary
      vasoconstriction (P<0.05) in the conscious state, and this response was
      attenuated (P<0.05) during isoflurane. Glibenclamide had no effect on the
      baseline pulmonary circulation, but it potentiated (P<0.05) the pulmonary
      vasoconstrictor response to hypotension in conscious and isoflurane-anesthetized
      dogs. CONCLUSIONS: These results indicate that K+ ATP-mediated pulmonary
      vasodilation and the pulmonary vasoconstrictor response to hypotension are
      attenuated during isoflurane anesthesia. Endogenous K+ ATP channel activation
      modulates the pulmonary vasoconstrictor response to hypotension in the conscious
      state, and this effect is preserved during isoflurane anesthesia.

PMID- 10078683
TI  - Mechanisms of isoflurane-induced myocardial preconditioning in rabbits.
AB  - BACKGROUND: Isoflurane has cardioprotective effects that mimic the ischemic
      preconditioning phenomenon. Because adenosine triphosphate-sensitive potassium
      channels and adenosine receptors are implicated in ischemic preconditioning, the
      authors wanted to determine whether the preconditioning effect of isoflurane is
      mediated through these pathways. METHODS: Myocardial infarct size was measured in
      seven groups of propofol-anesthetized rabbits, each subjected to 30 min of
      anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed
      only in the pretreatments given, and controls received no pretreatment. An
      ischemia-preconditioned group was pretreated with 5 min of coronary occlusion and
      15 min of reperfusion. An isoflurane-preconditioned group was pretreated with 15
      min end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus
      glyburide group was administered 0.33 mg/kg glyburide intravenously before
      isoflurane pretreatment. An isoflurane plus 8-(p-sulfophenyl)-theophylline (SPT)
      group received 7.5 mg/kg SPT intravenously before isoflurane. Additional groups
      were administered identical doses of glyburide or SPT, but they were not
      pretreated with isoflurane. Infarct size and area at risk were defined by
      staining. Data were analyzed by analysis of variance or covariance. RESULTS:
      Infarct size, expressed as a percentage of the area at risk (IS:AR) was 30.2+/
      11% (SD) in controls. Ischemic preconditioning and isoflurane preexposure reduced
      myocardial infarct size significantly, to 8.3+/-5% and 13.4+/-8.2% (P<0.05),
      respectively. Both glyburide and SPT pretreatment eliminated the preconditioning
      like effect of isoflurane (IS:AR = 30.0+/-9.1% and 29.2+/-12.6%, respectively; P
      = not significant). Neither glyburide nor SPF alone increased infarct size (IS:AR
      = 33.9+/-7.6% and 31.8+/-12.7%, respectively; P = not significant). CONCLUSIONS:
      Glyburide and SPT abolished the preconditioning-like effects of isoflurane but
      did not increase infarct size when administered in the absence of isoflurane.
      Isoflurane-induced preconditioning and ischemia-induced preconditioning share
      similar mechanisms, which include activation of adenosine triphosphate-sensitive
      potassium channels and adenosine receptors.

PMID- 10078684
TI  - Mechanisms of bronchoprotection by anesthetic induction agents: propofol versus
      ketamine.
AB  - BACKGROUND: Propofol and ketamine have been purported to decrease
      bronchoconstriction during induction of anesthesia and intubation. Whether they
      act on airway smooth muscle or through neural reflexes has not been determined.
      We compared propofol and ketamine to attenuate the direct activation of airway
      smooth muscle by methacholine and limit neurally mediated bronchoconstriction
      (vagal nerve stimulation). METHODS: After approval from the institutional review
      board, eight sheep were anesthetized with pentobarbital, paralyzed, and
      ventilated. After left thoracotomy, the bronchial artery was cannulated and
      perfused. In random order, 5 mg/ml concentrations of propofol, ketamine, and
      thiopental were infused into the bronchial artery at rates of 0.06, 0.20, and
      0.60 ml/min. After 10 min, airway resistance was measured before and after vagal
      nerve stimulation and methacholine given via the bronchial artery. Data were
      expressed as a percent of baseline response before infusion of drug and analyzed
      by analysis of variance with significance set at P< or =0.05. RESULTS: Systemic
      blood pressure was not affected by any of the drugs (P>0.46). Baseline airway
      resistance was not different among the three agents (P = 0.56) or by dose (P =
      0.96). Infusion of propofol and ketamine into the bronchial artery caused a dose
      dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction
      to 26+/-11% and 8+/-2% of maximum, respectively (P<0.0001). In addition, propofol
      caused a significant decrease in the methacholine-induced bronchoconstriction to
      43+/-27% of maximum at the highest concentration (P = 0.05) CONCLUSIONS: The
      local bronchoprotective effects of ketamine and propofol on airways is through
      neurally mediated mechanisms. Although the direct effects on airway smooth muscle
      occur at high concentrations, these are unlikely to be of primary clinical
      relevance.

PMID- 10078685
TI  - Continuous arterial P(O2) and P(CO2) measurements in swine during nitrous oxide
      and xenon elimination: prevention of diffusion hypoxia.
AB  - BACKGROUND: During nitrous oxide (N2O) elimination, arterial oxygen tension
      (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The
      authors questioned whether similar effects occur during xenon elimination.
      METHODS: Nineteen anesthetized and paralyzed pigs were mechanically ventilated
      randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70%
      N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and
      30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an
      indwelling arterial sensor. RESULTS: The PaO2 decreased from 119+/-10 mm Hg to
      102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to
      110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference
      (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during
      N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased
      (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and
      during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01).
      The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the
      xenon group (P<0.01). CONCLUSION: Diffusive hypoxia is unlikely to occur during
      recovery from xenon anesthesia, probably because of the low blood solubility of
      this gas.

PMID- 10078686
TI  - Interaction of bupivacaine and tetracaine with the sarcoplasmic reticulum Ca2+
      release channel of skeletal and cardiac muscles.
AB  - BACKGROUND: Although various local anesthetics can cause histologic damage to
      skeletal muscle when injected intramuscularly, bupivacaine appears to have an
      exceptionally high rate of myotoxicity. Research has suggested that an effect of
      bupivacaine on sarcoplasmic reticulum Ca2+ release is involved in its
      myotoxicity, but direct evidence is lacking. Furthermore, it is not known whether
      the toxicity depends on the unique chemical characteristics of bupivacaine and
      whether the toxicity is found only in skeletal muscle. METHODS: The authors
      studied the effects of bupivacaine and the similarly lipid-soluble local
      anesthetic, tetracaine, on the Ca2+ release channel-ryanodine receptor of
      sarcoplasmic reticulum in swine skeletal and cardiac muscle. [3H]Ryanodine
      binding was used to measure the activity of the Ca2+ release channel-ryanodine
      receptors in microsomes of both muscles. RESULTS: Bupivacaine enhanced (by two
      times at 5 mM) and inhibited (66% inhibition at 10 mM) [3H]ryanodine binding to
      skeletal muscle microsomes. In contrast, only inhibitory effects were observed
      with cardiac microsomes (about 3 mM for half-maximal inhibition). Tetracaine,
      which inhibits [3H]ryanodine binding to skeletal muscle microsomes, also
      inhibited [3H]ryanodine binding to cardiac muscle microsomes (half-maximal
      inhibition at 99 microM). CONCLUSIONS: Bupivacaine's ability to enhance Ca2+
      release channel-ryanodine receptor activity of skeletal muscle sarcoplasmic
      reticulum most likely contributes to the myotoxicity of this local anesthetic.
      Thus, the pronounced myotoxicity of bupivacaine may be the result of this
      specific effect on Ca2+ release channel-ryanodine receptor superimposed on a
      nonspecific action on lipid bilayers to increase the Ca2+ permeability of
      sarcoplasmic reticulum membranes, an effect shared by all local anesthetics. The
      specific action of tetracaine to inhibit Ca2+ release channel-ryanodine receptor
      activity may in part counterbalance the nonspecific action, resulting in moderate
      myotoxicity.

PMID- 10078687
TI  - Lamotrigine attenuates cortical glutamate release during global cerebral ischemia
      in pigs on cardiopulmonary bypass.
AB  - BACKGROUND: The dose-response effects of pretreatment with lamotrigine (a
      phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine
      cerebral ischemia model during cardiopulmonary bypass were studied. METHODS:
      Sagittal sinus catheters and cortical microdialysis catheters were inserted into
      anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were
      pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen
      minutes of global cerebral ischemia was produced, followed by 40 min of
      reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen
      metabolism was calculated using cerebral blood flow (radioactive microspheres)
      and arterial-venous oxygen content gradients. Concentrations of microdialysate
      glutamate and aspartate were quantified; electroencephalographic signals were
      recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were
      sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for
      metabolic profile. RESULTS: Lamotrigine caused dose-dependent reductions in
      systemic vascular resistance so that additional fluid was required to maintain
      venous return. Concentrations of glutamate and aspartate did not change during
      reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold
      increases, respectively, with lower doses. There were no intergroup differences
      in cerebral metabolism, electroencephalographic scores, cortical metabolites,
      brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and
      blood. CONCLUSIONS: Lamotrigine 50 mg/kg significantly attenuated excitatory
      neurotransmitter release during normothermic cerebral ischemia during
      cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine
      caused arterial and venous dilation, which limits its clinical usefulness.

PMID- 10078688
TI  - Influence of atracurium on the diaphragm mean action potential conduction
      velocity in canines.
AB  - BACKGROUND: It has been shown that progressive neuromuscular blockade (NMB)
      affects the electromyogram power spectrum and compound muscle action potential
      duration in skeletal muscle. These measures are linked to the mean muscle action
      potential conduction velocity (APCV), but no studies have confirmed a relation
      between the mean APCV and NMB. The aim of this study was to determine whether
      diaphragm mean APCV is affected by NMB. METHODS: The effects of NMB on diaphragm
      mean APCV were evaluated in five mongrel dogs. Progressive NMB was induced by
      slow intravenous infusion of atracurium. During spontaneous breathing, the
      diaphragm mean APCV was determined by electromyogram signals, in the time and
      frequency domains. The magnitude of NMB was quantified by the amplitude of the
      compound muscle action potential and by changes in muscle shortening during
      supramaximal stimulation of the phrenic nerve. RESULTS: Progressive NMB was
      associated with a decrease in diaphragm mean APCV. At approximately 70% reduction
      in the compound muscle action potential amplitude, diaphragm mean APCV had
      decreased more than 20%. Recovery after NMB was characterized by a restoration of
      the mean APCV to control values. CONCLUSION: This study shows that progressive
      NMB paralyzes motor units within the diaphragm in an orderly manner, and the
      blockade first affects muscle fibers with high APCV before it affects fibers with
      lower APCV.

PMID- 10078689
TI  - Primary and secondary hyperalgesia in a rat model for human postoperative pain.
AB  - BACKGROUND: Previously, the authors developed and characterized a rat model for
      postoperative pain to learn more about pain produced by incisions. In this study,
      the responses to heat and mechanical stimuli were evaluated directly on or
      adjacent to the incision and at varying distances from the incision. METHODS:
      Rats were anesthetized with halothane and incisions were made at different
      locations in the plantar aspect of the foot. The response frequency to a blunt
      mechanical stimulus, the withdrawal threshold to von Frey filaments (15-522 mN),
      and the withdrawal latency to radiant heat were measured. Rats were tested before
      surgery, 2 h later, and then daily through postoperative day 9. RESULTS: After
      plantar incision, persistent hyperalgesia was observed immediately adjacent to or
      directly on the incision to punctate and blunt mechanical stimuli, respectively.
      The withdrawal threshold to punctate stimuli applied 1 cm from the incision was
      decreased through postoperative day 1. In a transitional area, between the
      distant and adjacent sites, the withdrawal threshold was intermediate and the
      duration of hyperalgesia was transient. Heat hyperalgesia was persistent but
      present when the stimulus was applied to the site of injury but not to a distant
      site. CONCLUSION: Robust primary hyperalgesia to punctate and blunt mechanical
      stimuli was present. Hyperalgesia distant to the wound, or secondary
      hyperalgesia, occurred in response to punctate mechanical stimuli, was short
      lived, and required greater forces. These results suggest that the most
      persistent pain behaviors in this model are largely primary hyperalgesia.

PMID- 10078690
TI  - Sympathetic ganglionic blockade masks beneficial effect of isoflurane on
      histologic outcome from near-complete forebrain ischemia in the rat.
AB  - BACKGROUND: Isoflurane-anesthetized rats have better outcome from global cerebral
      ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors
      wanted to determine whether circulating catecholamine concentrations depend on
      the anesthetic agent and whether sympathetic ganglionic blockade affects
      anesthetic-mediated differences in outcome from near-complete forebrain ischemia.
      METHODS: For two different experiments, normothermic Sprague-Dawley rats that had
      fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg
      mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized
      with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous
      oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In
      experiment 1, arterial plasma catecholamine concentrations were measured before,
      at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n
      = 15) underwent histologic analysis 5 days after ischemia. RESULTS: In experiment
      1, intraischemic increases in plasma norepinephrine and epinephrine levels were
      28 and 12 times greater in the fentanyl-nitrous oxide group than in the
      isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma
      catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the
      mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl
      nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the
      beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were
      made in the cortex. CONCLUSIONS: Isoflurane attenuated the peripheral sympathetic
      response to ischemia and improved histologic outcome compared with fentanyl and
      nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic
      blockade. The beneficial effects of isoflurane may result from a neuroprotective
      influence of an intermediate sympathetic response that is abolished by
      trimethaphan.

PMID- 10078691
TI  - FDA's role in anesthetic drug development.

PMID- 10078692
TI  - Vassily von Anrep, forgotten pioneer of regional anesthesia.

PMID- 10078693
TI  - Practice guidelines for preoperative fasting and the use of pharmacologic agents
      to reduce the risk of pulmonary aspiration: application to healthy patients
      undergoing elective procedures: a report by the American Society of
      Anesthesiologist Task Force on Preoperative Fasting.

PMID- 10078694
TI  - Cold urticaria associated with intraoperative hypotension and facial edema.

PMID- 10078695
TI  - Hemofiltration in parallel to the venovenous bypass circuit for oliguric
      hypervolemia during liver transplantation.

PMID- 10078696
TI  - Respiratory compromise and dramatic chest X-ray changes during general anesthesia
      in a patient with a bronchogenic cyst.

PMID- 10078697
TI  - Subcortical somatosensory evoked potentials fail to detect ischemia at C1-2.

PMID- 10078698
TI  - Preventing complications during percutaneous tracheostomy.

PMID- 10078699
TI  - Vascular effects of isoflurane: no inconsistency between data.

PMID- 10078700
TI  - Renal cysteine conjugate beta-lyase and compound A nephrotoxicity: minimal
      evidence for an association.

PMID- 10078701
TI  - Does the variability in the volume of lumbosacral cerebrospinal fluid affect
      sensory block extent of spinal anesthesia?

PMID- 10078702
TI  - The cuffed oropharyngeal airway and management of the difficult airway.

PMID- 10078703
TI  - Comparison of pH-stat and alpha-stat cardiopulmonary bypass on cerebral
      oxygenation and blood flow in relation to hypothermic circulatory arrest in
      piglets.

PMID- 10078704
TI  - Lugol's solution: a potent eye irritant.

PMID- 10078705
TI  - Antifibrinolytic agents make alpha1- and beta2-microglobulinuria poor markers of
      postcardiac surgery renal dysfunction.

PMID- 10078706
TI  - The WuScope technique for endotracheal tube exchange.

PMID- 10078707
TI  - Venous cannulation in small infants: a simple method to improve success.

PMID- 10078708
TI  - Opening a window on cerebral cholinergic function: PET imaging of
      acetylcholinesterase.

PMID- 10078709
TI  - Placebo-controlled studies in neurology: where do they stop?

PMID- 10078710
TI  - Founders and CAG repeats: cause or effect?

PMID- 10078711
TI  - Practice parameter: electrodiagnostic studies in ulnar neuropathy at the elbow.
      American Association of Electrodiagnostic Medicine, American Academy of
      Neurology, and American Academy of Physical Medicine and Rehabilitation.

PMID- 10078712
TI  - In vivo mapping of cerebral acetylcholinesterase activity in aging and
      Alzheimer's disease.
AB  - OBJECTIVE: To validate an in vivo method for mapping acetylcholinesterase (AChE)
      activity in human brain, preparatory to monitoring inhibitor therapy in AD.
      BACKGROUND: AChE activity is decreased in postmortem AD brain. Lacking a reliable
      in vivo measure, little is known about central activity in early AD, when the
      disease is commonly targeted by AChE inhibitor drug therapy. METHODS: Intravenous
      N-[11C]methylpiperidin-4-yl propionate ([11C]PMP) served as an in vivo AChE
      substrate. AChE activity was defined using cerebral PET for tracer kinetic
      estimates of the local rate of [11C]PMP hydrolysis in 26 normal controls and 14
      patients with AD. Eleven AD patients also had concomitant in vivo cerebral
      measures of vesicular acetylcholine transporter (cholinergic terminal) density
      and glucose metabolism. RESULTS: Cerebral AChE activity measures 1) were
      independent of changes in tracer delivery to cerebral cortex; 2) agreed with
      reported postmortem data concerning normal relative cerebral distributions,
      absence of large age-effect in normal aging, and deficits in AD; 3) correlated in
      AD cerebral cortex with concomitant in vivo measures of cholinergic terminal
      deficits, but not with metabolic deficits; and 4) agreed quantitatively with
      predicted level of cerebral AChE inhibition induced by physostimine. CONCLUSIONS:
      This in vivo PET method provided valid measures of central AChE activity in
      normal subjects and AD patients. Applied in early AD, it should facilitate
      inhibitor treatment by confirming central inhibition, optimizing drug dosage,
      identifying likely responders, and testing surrogate markers of therapeutic
      response.

PMID- 10078713
TI  - Efficacy and safety of eptastigmine for the treatment of patients with
      Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the efficacy and safety of eptastigmine in patients with
      moderate to moderately severe AD. BACKGROUND: Eptastigmine is a centrally acting
      cholinesterase inhibitor. METHODS: The study was carried out according a
      multicenter, randomized, double-blinded, placebo-controlled, parallel-group
      design. Patients received a 24-week treatment with placebo or eptastigmine 15 mg
      or 20 mg three times daily after a 4-week, stepwise dose escalation. The effects
      of treatment on cognition, global function, and activities of daily living were
      evaluated with the Alzheimer's Disease Assessment Cognitive Subscale (ADAS-Cog),
      the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus), and the
      Instrumental Activities of Daily Living scale (IADL), respectively. RESULTS:
      Thirty-six centers recruited 491 patients: 164 on placebo, 166 on eptastigmine 15
      mg three times daily, and 161 on eptastigmine 20 mg three times daily.
      Percentages of patients completing double-blinded treatment were 87% in the
      placebo group and 86% in both the eptastigmine-treated groups. At the end of
      treatment, the intent-to-treat analysis on 463 patients showed a dose-dependent
      effect of eptastigmine on all efficacy variables, with a statistically
      significant effect of the 20 mg three times daily dose compared with placebo on
      the ADAS-Cog, CIBIC-Plus, and IADL. Patients on eptastigmine 15 mg three times
      daily performed significantly better than placebo-treated patients only on the
      ADAS-Cog. Eleven patients on placebo (7%), 13 patients on eptastigmine 15 mg
      three times daily (8%), and 12 patients on eptastigmine 20 mg three times daily
      (8%) discontinued study treatment because of adverse events. Adverse events were
      recorded in 49% of patients on placebo compared with 54% on eptastigmine 15 mg
      three times daily and 48% on eptastigmine 20 mg three times daily. Cholinergic
      side effects (nausea, vomiting, diarrhea, and abdominal pain) were reported with
      similar frequency in the eptastigmine- and placebo-treated patients. There was a
      dose-dependent transient and mild neutropenic effect associated with eptastigmine
      treatment, and one patient on 20 mg three times daily had an asymptomatic
      pancytopenia. CONCLUSIONS: Eptastigmine produces significant cognitive, clinical,
      and functional benefits in patients with probable AD. Although the cholinergic
      tolerability of eptastigmine was found to be favorable, its potential adverse
      hematologic effects limit its clinical utility.

PMID- 10078714
TI  - Dementia is a major predictor of death among the Italian elderly. ILSA Working
      Group. Italian Longitudinal Study on Aging.
AB  - BACKGROUND: Neurologic diseases are rarely listed on death certificates because
      death is more often attributed to cardiovascular and pneumonic events occurring
      during terminal stages. OBJECTIVE: To evaluate the effect of major age-associated
      neurologic and non-neurologic diseases on survival in a cohort of Italian
      elderly. METHODS: A population-based multicenter survey, carried out in eight
      Italian municipalities, with a sample of 5,632 individuals aged 65 to 84 years.
      The entire sample was screened for all the diseases under study, and all
      individuals were interviewed about risk factors. Those who screened positive
      underwent clinical assessments by specialists. Two years after the baseline
      survey, the study population was followed up to determine the vital status either
      directly from the individuals or from proxy respondents. A copy of the death
      certificate was obtained for each individual who had died. The risk of dying
      (mortality risk ratio [MRR]) was calculated using the Cox proportional hazards
      model in which we included all the diseases under study, age, gender, and years
      of education. RESULTS: At follow-up (mean duration 26.7 +/- 5.4 months) 444
      individuals had died. The Cox proportional hazards model selected the following
      as significant predictors of death: age (for year of age MRR = 1.12; 95%
      confidence interval [CI], 1.08 to 1.15), male gender (MRR = 1.72; 95% CI, 1.27 to
      2.34), institutionalization (MRR = 4.17; 95% CI, 2.20 to 7.94), dementia (MRR =
      3.61; 95% CI, 2.55 to 5.11), neoplasm (MRR = 2.01; 95% CI, 1.20 to 3.38), heart
      failure (MRR = 1.87; 95% CI, 1.27 to 2.76), and diabetes (MRR = 1.62; 95% CI,
      1.12 to 2.34). CONCLUSIONS: These data provide further evidence on the malignancy
      of dementia, which proved the major predictor of death in the elderly, with an
      MRR higher than neoplastic diseases and other severe age-associated conditions.

PMID- 10078715
TI  - Nursing home placement is related to dementia progression: experience from a
      clinical trial. Alzheimer's Disease Cooperative Study.
AB  - OBJECTIVES: To examine the relationship between nursing home placement (NHP) and
      measures of change in other well-established clinical disease assessments in a
      longitudinal study of patients with probable AD. BACKGROUND: NHP is a common,
      major milestone in the natural history of AD. NHP is a readily identified event
      that can be accurately dated. NHP can be used in survival analyses, which are an
      efficient means of determining efficacy in clinical trials. NHP usually occurs in
      the setting of severe AD, but in cross-sectional studies, the strength of the
      association with disease severity has been controversial. DESIGN/METHODS: We used
      data from 341 AD patients who were enrolled in a recently published clinical
      trial of selegiline and tocopherol. At entry, all were rated as Clinical Dementia
      Rating (CDR) stage 2, were community-dwelling, and had an identified caregiver.
      Patients were followed at 3-month intervals for 2 years. We examined the
      relationship between four measures of dementia severity and a measure of
      behavioral dysfunction and NHP. The measures included changes in CDR status,
      changes in activities of daily living performance, changes from baseline to last
      measurement in dependence level, changes from baseline to last measurement on the
      Blessed Dementia Rating Scale (BDRS) score, and changes from baseline to last
      measurement on the total score and subscales of the Behavior Rating Scale for
      Dementia (BRSD). Statistical models were used to assess the strength of the
      associations. RESULTS: At the end of the 2-year period, 33% of patients had been
      institutionalized. The NHP patients did not differ at baseline from the not-NHP
      patients in gender, age, caregiver status, duration of illness, CDR sum of boxes,
      BDRS, or dependence level. The NHP patients had a lower baseline Mini-Mental
      State Examination score and a slightly worse BRSD total score. Patients reaching
      CDR3 were eight times more likely to be institutionalized than those who remained
      at CDR2. The change scores on all four dementia severity measures were strongly
      associated with NHP; the change score on the BRSD and its subscales were not. On
      the other hand, adverse events that included a behavioral disturbance, especially
      agitation, were associated with NHP. CONCLUSION: These data show that NHP closely
      reflects dementia progression in the context of a clinical trial. Coupled with
      the high face validity of NHP as a milestone of severe dementia, NHP is a valid
      primary outcome measure for AD clinical trials.

PMID- 10078716
TI  - Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and
      without dementia.
AB  - OBJECTIVE: To determine whether first-degree relatives of PD patients with
      dementia were at increased risk for the development of AD compared with first
      degree relatives of nondemented PD patients and nondemented normal subjects from
      the community. METHODS: A structured family history interview was administered to
      146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal
      subjects from the community to ascertain the presence of AD among parents and
      siblings of these subjects. Cox proportional hazards models with double censoring
      techniques for missing information were used to model the risk of AD among
      relatives. RESULTS: No increase in risk of AD was found among parents of patients
      with PD and dementia or parents of nondemented PD patients compared with parents
      of normal subjects. However, siblings of demented PD patients were three times as
      likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p <
      0.04) as siblings of normal subjects to develop AD. When only siblings >65 years
      of age were considered, there was a fivefold increase in risk of AD among
      siblings of demented PD patients compared with siblings of normal subjects (RR =
      4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for
      female relatives, regardless of whether the woman was a relative of a demented PD
      patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE
      genotype did not affect dementia status among relatives. CONCLUSIONS: The
      increased risk of AD in siblings of demented PD patients compared with siblings
      of normal subjects supports the possibility of familial aggregation of AD and PD
      with dementia.

PMID- 10078717
TI  - Neurobiological correlates of a putative risk allele for Alzheimer's disease on
      chromosome 12q.
AB  - OBJECTIVE: To explore the clinical, neuropathologic, and neurochemical correlates
      of the D12S1045 91 base pair (bp) allele in a group of 50 autopsy-confirmed cases
      of AD who lacked other concomitant brain diseases. BACKGROUND: In a previous
      genome survey for novel risk loci for typical-onset (> or =60 years) AD conducted
      at 10 cM resolution, we detected associations of alleles at six microsatellite
      loci with AD. These included the 91bp allele of the D12S1045 locus that resides
      in the telomeric region of 12q. METHODS: Clinical assessment was performed as
      part of a longitudinal study of AD and related disorders. Standardized pathologic
      methods, genotyping, morphometry, and neurochemical analyses were performed with
      postmortem brain tissue. RESULTS: Patients with AD who carried the D12S1045 91bp
      allele manifested earlier ages at symptomatic onset and death, greater densities
      of cortical neurofibrillary tangles, and substantially greater reductions in
      cortical dopamine levels compared to noncarriers. A dosage effect of the number
      of D12S1045 91bp alleles on cortical dopamine levels was also observed.
      CONCLUSIONS: Carrying the D12S1045 91bp allele was associated with greater
      clinical, neuropathologic, and neurochemical severity independent of sex and APOE
      genotype. These findings suggest that a novel susceptibility gene for AD resides
      at or in close proximity to the D12S1045 locus.

PMID- 10078718
TI  - Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for
      partial seizures.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oxcarbazepine in a placebo
      control trial. METHODS: A multicenter, double-blind, randomized, placebo-control,
      two-arm parallel group, monotherapy design was used to compare oxcarbazepine
      administered 1,200 mg twice daily to placebo in hospitalized patients with
      refractory partial seizures, including simple and complex partial seizures and
      partial seizures evolving to secondarily generalized seizures. Patients exited
      the trial after completing the 10-day double-blind treatment phase or after
      experiencing four partial seizures, two new-onset secondarily generalized
      seizures, serial seizures, or status epilepticus, whichever came first. RESULTS:
      Analysis of the primary efficacy variable--time to meeting one of the exit
      criteria--showed a statistically significant effect in favor of oxcarbazepine (p
      = 0.0001). The secondary efficacy variables--percentage of patients who met one
      of the exit criteria (p = 0.0001) and total partial seizure frequency per 9 days
      during the double-blind treatment (p = 0.0001)--were also statistically
      significant in favor of oxcarbazepine. CONCLUSION: These results demonstrate that
      oxcarbazepine given as monotherapy is effective and safe for the treatment of
      partial seizures in this paradigm.

PMID- 10078719
TI  - Improvement in adult-onset Rasmussen's encephalitis with long-term
      immunomodulatory therapy.
AB  - OBJECTIVE: To study the immediate and chronic effects of high-dose, long-term
      human i.v. immunoglobulin (h i.v.Ig) therapy in two patients with advanced adult
      onset Rasmussen's encephalitis (RE). BACKGROUND: Despite advances in our
      understanding of the autoimmune pathogenesis of RE, medical options for chronic
      treatment are limited. METHODS: In an open-label treatment trial, treatment
      started with monthly cycles of high-dose h i.v.Ig (0.4 g/kg/d for 5 days)
      followed by maintenance therapy (0.4 g/kg 1 day each month) after the patients'
      conditions began to improve. Outcome measures included clinical, psychological,
      functional, and laboratory assessments before and at relevant intervals
      throughout 1 year of treatment. RESULTS: In both patients, unrelenting
      pretreatment deterioration halted, and after this they displayed striking
      improvements in seizure control, hemiparesis, and cognition that produced useful
      recovery of function. Improvements were delayed until after 2 to 4 monthly cycles
      of high-dose h i.v.Ig and continued when patients switched to maintenance
      treatment. Their recoveries were accompanied by increased cerebral perfusion on
      interictal SPECT and suppression of inflammatory markers in CSF. CONCLUSIONS: h
      i.v.Ig can be a useful, possibly disease-modifying, long-term therapy for adult
      onset RE that should be considered before radical surgery is performed. Because
      improvements can be delayed, we propose guidelines for intensive and prolonged
      trials of immunomodulatory therapy in adults with this syndrome.

PMID- 10078720
TI  - Postictal nose-rubbing in the diagnosis, lateralization, and localization of
      seizures.
AB  - BACKGROUND: Semiology is very useful in the diagnosis and classification of
      seizures. Some clinical signs occur primarily with specific localization-related
      epilepsies. OBJECTIVE: To evaluate postictal nose-rubbing as a potential
      diagnostic sign and a potential lateralizing or localizing indicator. METHODS: We
      reviewed presurgical prolonged video-EEG results of 50 consecutive patients with
      right temporal lobe epilepsy (TLE), 50 consecutive patients with left TLE, 50
      consecutive patients with frontal lobe epilepsy, 11 consecutive patients with
      generalized epilepsy, and 100 consecutive patients with nonepileptic events.
      Videotapes of all events were reviewed independently by two investigators who
      were blinded to the results of the monitoring. The episodes of nose-rubbing and
      the hand with which the patient rubbed the nose were recorded. RESULTS: Nose
      rubbing occurred in 25 of 50 (50%) right TLE patients and in 21 of 50 (42%) left
      TLE patients. Approximately 90% of patients rubbed his or her nose with the
      ipsilateral hand. Nose-rubbing occurred in 5 of 50 (10%) frontal lobe epilepsy
      patients. Nose-rubbing was not seen in any patient with generalized epilepsy or
      nonepileptic events. Postictal nose-rubbing did not occur after secondarily
      generalized seizures. CONCLUSIONS: Nose-rubbing is an easily observed phenomenon,
      has high interobserver reliability, and provides useful lateralizing information
      in patients with TLE. It was less frequently seen in extratemporal lobe epilepsy
      and was not seen after generalized seizures or nonepileptic events.

PMID- 10078721
TI  - Serum neuron-specific enolase in the major subtypes of status epilepticus.
AB  - OBJECTIVES: To determine the relative magnitudes of neuron-specific enolase (NSE)
      levels after complex partial status epilepticus (SE), absence SE, generalized
      convulsive SE, and subclinical generalized convulsive SE (frequently referred to
      as acute symptomatic myoclonic status epilepticus). BACKGROUND: NSE is a marker
      of acute brain injury and blood-brain barrier dysfunction, which is elevated in
      SE. METHODS: Serum NSE levels were drawn in 31 patients 1, 2, 3, and 7 days after
      SE. Patients were classified as acute symptomatic or remote symptomatic, and the
      duration and outcome of SE were determined and correlated with the peak NSE
      level. RESULTS: NSE was elevated significantly in all four subtypes of SE, but
      NSE levels were highest in complex partial and subclinical SE. The mean peak NSE
      level for the complex partial SE group was 23.88 ng/mL (n = 12), 21.5 ng/mL for
      absence SE (n = 1), 14.10 ng/mL for the generalized convulsive SE group (n = 12),
      and 37.83 ng/mL for the subclinical SE group (n = 6), all of which was
      significantly higher than normal control subjects (5.02 ng/mL). Outcome was
      significantly different between the three groups (p = 0.0007), and was
      significantly worse for subclinical SE (p = 0.0005, subclinical versus
      generalized convulsive SE). CONCLUSION: Serum NSE levels were highest in complex
      partial and subclinical generalized convulsive SE. The extremely high levels of
      NSE in subclinical SE reflect the severity of the acute neurologic insults and
      poor outcome common to subclinical SE. High NSE levels in complex partial SE
      reflects the long duration of SE in this subgroup, and potential for brain
      injury.

PMID- 10078722
TI  - Impaired methionine synthesis and hypomethylation in rats exposed to valproate
      during gestation.
AB  - BACKGROUND: The antiepileptic drug valproic acid (VPA) may be teratogenic. The
      mechanism of teratogenicity remains unclear, but it has been hypothesized that
      VPA interferes with folate metabolism. OBJECTIVE: To study the effect of VPA on
      the methionine cycle and transmethylation reactions in pregnant rats. METHODS:
      Wistar rats were treated with VPA (300 mg/kg/day) on gestation days 8, 9, and 10,
      alone or in combination with folinic acid (FOL, 4 mg/kg/day) on gestation days 8,
      9, and 10 or S-adenosylmethionine (SAM, 10 mg/kg/day) throughout gestation days 1
      to 10. RESULTS: VPA induced a reduction in maternal methionine serum
      concentration (p < 0.05) caused by a 24% reduction of methionine synthase
      activity in liver. This provoked hepatic DNA hypomethylation, although the
      methylation ratio (S-adenosylmethionine/S-adenosylhomocysteine) was not altered.
      Homocysteine, folate, and vitamin B12 serum concentrations, as well as methionine
      adenosyltransferase and betaine homocysteine methyltransferase hepatic
      activities, did not change. In fetuses exposed to VPA, no effect was observed in
      hepatic methionine content, but the methylation ratio was reduced (p < 0.01),
      leading again to hepatic DNA hypomethylation. Coadministration of FOL prevented
      VPA-induced alterations in methionine synthesis and corrected fetal DNA
      hypomethylation. By contrast, SAM did not exert a protective effect on fetal DNA
      methylation. CONCLUSION: Impaired methionine synthesis and DNA hypomethylation
      may be involved in VPA-induced teratogenesis.

PMID- 10078723
TI  - Abnormal performance on the PD test battery by asymptomatic first-degree
      relatives.
AB  - OBJECTIVE: To determine whether a sensitive and specific battery of tests (PD
      Battery) could identify a subset of asymptomatic first-degree relatives (FDRs) of
      PD patients who were significantly more impaired than age-matched normal control
      (NC) subjects. The PD Battery incorporates tests of motor function, olfaction,
      and mood. In previous studies, it has shown high specificity and sensitivity in
      distinguishing mildly affected PD patients from NC subjects. METHODS: The PD
      Battery and regression analysis-derived scoring equations were applied to
      asymptomatic FDRs. RESULTS: Eighty FDRs and 100 NC subjects were tested. Of the
      FDRs, 22.5% scored in the abnormal range, and 9% of NC subjects had abnormal
      scores. This difference was statistically significant. Further analysis
      demonstrated that FDRs with abnormal scores on the PD Battery differed on all
      three components of the test battery from FDRs who had normal scores. Among the
      sons and daughters whose scores were abnormal, there was a much higher prevalence
      of the affected parent being the father. CONCLUSIONS: The proportion of FDRs who
      demonstrated abnormal performance on the PD Battery was greater than that of NC
      subjects. Thus, the PD Battery may detect the asymptomatic carrier state or risk
      for PD. Sons and daughters whose scores were in the abnormal range were more
      likely to have fathers with PD.

PMID- 10078724
TI  - Loss of long-duration response to levodopa over time in PD: implications for
      wearing-off.
AB  - OBJECTIVE: To determine the modifications of the long-duration response to
      levodopa in PD over a 1-year period. BACKGROUND: The development of predictable
      motor fluctuations in PD has been attributed mainly to modifications over time of
      the short-duration response to levodopa, whereas the role of the long-duration
      response has not been widely investigated. METHODS: In 17 patients with PD the
      authors examined prospectively both the short-duration response and the long
      duration response to levodopa under standardized conditions on two different
      occasions separated by a period of approximately 1 year (11.7 +/- 3.6 months).
      RESULTS: At the end of the follow-up period, the short-duration response
      increased in magnitude but did not change significantly in duration. A total of
      24% of patients lost the long-duration response 1 year after their first
      examination, but a sustained long-duration response could be reestablished by
      shortening the interdose interval for levodopa intake. Moreover, the duration of
      the long-duration response after discontinuation of treatment became
      significantly shorter during 1 year. CONCLUSION: Modifications of the long
      duration response may have a pivotal role in generating a fluctuating response,
      and suggest that therapeutic strategies based on maintenance of the long-duration
      response should be sought to avoid the appearance of motor fluctuations.

PMID- 10078725
TI  - Simultaneous repetitive transcranial magnetic stimulation does not speed fine
      movement in PD.
AB  - OBJECTIVE: To reevaluate the effect of subthreshold repetitive transcranial
      magnetic stimulation (rTMS) on concurrent fine movement in PD. BACKGROUND: A
      previous study showed a beneficial effect of rTMS on the performance of six
      patients with PD on the Grooved Pegboard test. METHODS: The authors repeated this
      experiment in 11 patients with idiopathic PD who performed the test while the
      stimulating coil discharged continuously at 5 Hz, either over the contralateral
      motor cortex at just below the threshold for movement, or in the air near the
      head as a control. Patients were tested twice under both conditions. RESULTS:
      Although some patients performed faster with rTMS, others showed the opposite
      effect. There was no significant effect of rTMS in the group, nor did baseline
      performance or the order of conditions interact with the effect of rTMS.
      CONCLUSIONS: Based on this larger and more comprehensive study, simultaneous, 5
      Hz subthreshold rTMS over the motor cortex does not have consistent or
      potentially therapeutic effects on movement in PD.

PMID- 10078726
TI  - D1 receptor blockade improves L-dopa-induced dyskinesia but worsens parkinsonism
      in MPTP monkeys.
AB  - OBJECTIVE: To determine whether dopamine (DA) D1 or DA D2 receptors are
      associated predominantly with the antiparkinsonian versus the dyskinetic effect
      of levodopa. METHODS: The authors used four L-dopa-primed, dyskinetic 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-exposed monkeys to test whether acute and
      selective blockade of the DA D1 receptor subtype, using SCH 23390 and NNC 01-112,
      could reduce L-dopa-induced dyskinesias without altering the relief of symptoms.
      Blockade of DA receptors using sulpiride (D2) and clozapine (D1-D2-like) was
      studied for comparison. RESULTS: With the notable exception of the lowest dose of
      clozapine tested, coadministration of DA D1 or D2 antidopaminergic agents with L
      dopa reduced the L-dopa-induced dyskinesias but also caused a return of
      parkinsonian disability. Prolonged latencies from intake of a single oral dose of
      L-dopa to turning "on," decreased duration of the "on" state, and a complete
      failure to induce benefit was also observed. CONCLUSION: Low-dose clozapine could
      be an effective adjunct to reduce L-dopa-induced dyskinesias without altering the
      relief of parkinsonian symptoms. Interactions with many neurotransmitter systems
      may explain the better pharmacologic profile of clozapine, including DA D4
      (rather than D1), serotonin, acetylcholine, and noradrenaline. Neither
      dyskinesias nor antiparkinsonian effects can be ascribed solely to the D2 or D1
      receptor. Thus, some cooperation between the two receptors appears necessary for
      these behavioral effects.

PMID- 10078727
TI  - Susceptibility to neuroleptic malignant syndrome in Parkinson's disease.
AB  - OBJECTIVE: To determine susceptibility to neuroleptic malignant syndrome (NMS) in
      patients with PD in relation to central monoamine metabolism. METHODS: CSF levels
      of homovanillic acid (HVA), 3-methoxy-4-hydroxy phenyletilene glycol (MHPG), and
      5-hydroxyindole acetic acid (5-HIAA) were assayed in 98 PD patients (mean age,
      77.2 years), including 11 patients with a prior NMS-like episode, by high
      performance liquid chromatography with electrochemical detection. RESULTS:
      Patients with a previous NMS-like episode had worse parkinsonian disability as
      measured by Hoehn & Yahr scale (3.7 +/- 0.8 versus 3.0 +/- 1.1; p = 0.038) and
      lower CSF HVA levels (20.9 +/- 17.3 versus 44.7 +/- 22.2 ng/mL; p = 0.001)
      compared to those without, despite similar age, disease duration, and daily
      dosages of antiparkinsonian drugs between groups. Logistic regression analysis
      showed that the CSF HVA level (p = 0.008), but not 5-HIAA level (p = 0.621), was
      significantly and independently related to NMS, and that the MHPG level (p =
      0.070) was tendentially associated with the disorder. Odds ratios (95% confidence
      intervals) corresponding to 10 ng/mL increment in CSF HVA, MHPG, and 5-HIAA
      levels were 0.30 (0.13 to 0.73), 4.03 (0.89 to 18.2) and 1.29 (0.47 to 3.58),
      respectively. CONCLUSIONS: Central dopaminergic and possible noradrenergic
      activity contributes to NMS development in an elderly population of PD patients.
      Measuring CSF levels of monoamine metabolites may provide a means for identifying
      NMS susceptibility in PD patients.

PMID- 10078728
TI  - Neurologic side effects in neuroleptic-naive patients treated with haloperidol or
      risperidone.
AB  - OBJECTIVE: To compare the side effect profile of risperidone with that of oral
      haloperidol in patients with no previous exposure to antipsychotic drugs (APDs).
      BACKGROUND: Early studies suggested that the APD risperidone may have a side
      effect profile comparable with that of placebo. These early studies involved
      patients with chronic schizophrenia and a long history of APD use. Very little
      information is available regarding the neurologic side effects of risperidone in
      patients without previous APD exposure. METHODS: The authors prospectively
      studied 350 consecutive neuroleptic-naive patients admitted to their acute-care
      psychiatry service; 34 of these were treated with risperidone (mean dose, 3.2
      mg/d) and 212 were treated with low-dose haloperidol (mean dose 3.7 mg/d). All
      patients were assessed on admission and twice weekly thereafter using rating
      scales for dystonia, parkinsonism, akathisia, and dyskinesia. RESULTS: The
      incidence and severity of dystonic reactions, akathisia, parkinsonism, and
      dyskinesia were comparable in the risperidone- and haloperidol-treated groups.
      CONCLUSIONS: The neurologic side effect profile of low-dose risperidone is
      comparable with that of haloperidol in patients receiving APDs for the first
      time. Risperidone may not be a useful alternative to typical APDs for patients
      with PD and psychosis.

PMID- 10078729
TI  - EEG and cardiac activation during periodic leg movements in sleep: support for a
      hierarchy of arousal responses.
AB  - OBJECTIVE: To investigate other physiologic changes that occur with periodic leg
      movements during sleep (PLMS) that might be considered to be more sensitive
      indices of sleep fragmentation. BACKGROUND: Although PLMS are associated with
      recurrent microarousals (MA), the frequency of PLMS with MA does not correlate
      with objective daytime sleepiness. It is postulated that the lack of correlation
      results from the low sensitivity of the standard criteria used to score MA.
      METHODS: Ten drug-free patients with a polygraphic and clinical diagnosis of
      restless legs syndrome (RLS) and PLMS were examined. The EEG correlates of PLMS
      were analyzed by visual scoring and spectral analysis during PLMS that ended in a
      visible microarousal (PLMS with MA) or not (PLMS without MA). The R-R interval in
      the EKG signal was also examined. RESULTS: A total of 34% of PLMS were associated
      with MA lasting >3 seconds, and 3% of PLMS were associated with MA lasting <3
      seconds. Although PLMS with MA were associated with an increase in alpha
      activity, for PLMS without MA a significant increase in delta and theta activity
      was present. Both types of PLMS induced a shortening of the R-R interval; this
      was particularly more marked for PLMS with MA. CONCLUSIONS: First, visual scoring
      of MA that include a duration of less than 3 seconds has little effect on the
      detection of PLMS with MA. Second, EEG activation and tachycardia are present
      during both types of PLMS. Third, a hierarchy in the arousal response is present
      going from autonomic activation to bursts of delta activity to alpha activity to
      a full awakening.

PMID- 10078730
TI  - Cerebellar reorganization following cortical injury in humans: effects of lesion
      size and age.
AB  - OBJECTIVE: The authors investigated chronic cerebellar reorganization following
      unilateral cortical lesions in children and adults using PET to measure
      benzodiazepine receptor (BZR) binding with [11C]flumazenil (FMZ) and glucose
      metabolism with 2-deoxy-2[18F]fluoro-D-glucose (FDG). BACKGROUND: Crossed
      cerebellar diaschisis (CCD) is defined as decreased metabolism or blood flow in
      the cerebellum contralateral to a cortical insult measured by functional
      neuroimaging, and is typically seen in adults with large frontal or parietal
      lesions. The authors previously reported that CCD of glucose metabolism was not
      as prominent in children as in adults, and that some children showed a
      paradoxical pattern of increased glucose utilization in cerebellar cortex
      contralateral to the cortical lesion. The current study investigated whether CCD
      is associated with alterations in the gamma-aminobutyric acid (GABA(A))/BZR
      complex. METHODS: Patients with frontal lesions alone or with parietal lesions
      were compared with patients with temporal lesions, which are typically not
      associated with CCD. RESULTS: Children with lesion onset before 1 year of age
      showed significantly higher glucose utilization in contralateral posterior
      quadrangular and superior semilunar lobules of cerebellar cortex than did adults.
      Two patterns of change in cerebellar BZR binding were seen in children: 1) Five
      of 10 children showed increased BZR binding in the dentate nucleus contralateral
      to the lesion, and 2) the remaining five children showed no increase in dentate
      nucleus BZR binding but showed increased binding in the lateral lobules of the
      cerebellar cortex contralateral to the lesion. Adults showed increased binding
      only in contralateral dentate nucleus and not in cerebellar cortex. The size and
      severity of the supratentorial lesion, as well as age at the time of injury, were
      important factors in these findings. CONCLUSIONS: Reorganization of GABA-mediated
      mechanisms and glucose metabolism in cerebellum following cortical injury differs
      with size of lesion and age at the time of injury.

PMID- 10078731
TI  - Language dominance determined by whole brain functional MRI in patients with
      brain lesions.
AB  - BACKGROUND: Functional MRI (fMRI) is of potential value in determining hemisphere
      dominance for language in epileptic patients. OBJECTIVE: To develop and validate
      an fMRI-based method of determining language dominance for patients with a wide
      range of potentially operable brain lesions in addition to epilepsy. METHODS:
      Initially, a within-subjects design was used with 19 healthy volunteers (11
      strongly right-handed, 8 left-handed) to determine the relative lateralizing
      usefulness of three different language tasks in fMRI. An automated, hemispheric
      analysis of laterality was used to analyze whole brain fMRI data sets. To
      evaluate the clinical usefulness of this method, we compared fMRI-determined
      laterality with laterality determined by Wada testing or electrocortical
      stimulation mapping, or both, in 23 consecutive patients undergoing presurgical
      evaluation of language dominance. RESULTS: Only the verb generation task was
      reliably lateralizing. fMRI, using the verb generation task and an automated
      hemispheric analysis method, was concordant with invasive measures in 22 of 23
      patients (12 Wada, 11 cortical stimulation). For the single patient who was
      discordant, in whom a tumor involved one-third of the left hemisphere, fMRI
      became concordant when the tumor and its reflection in the right hemisphere were
      excluded from laterality analysis. No significant negative correlation was
      obtained between lesion size and strength of laterality for the patients with
      lesions involving the dominant hemisphere. CONCLUSION: This fMRI method shows
      potential for evaluating language dominance in patients with a variety of brain
      lesions.

PMID- 10078732
TI  - Neurophysiologic follow-up of long-term dietary treatment in adult-onset
      adrenoleukodystrophy.
AB  - OBJECTIVE: To monitor the effects of dietary treatment in adult-onset
      adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and
      motor evoked potentials (MEPs). BACKGROUND: SEPs and MEPs have proved useful in
      revealing signs of progressively severe, central dying-back axonopathy in early
      stages of adult-onset ALD. METHODS: Eight patients with adult-onset ALD underwent
      clinical examination, brain and spine MRI, and SEP and MEP studies before and
      after 3 years of Lorenzo's oil dietary therapy. RESULTS: Before treatment, brain
      MRI was normal in five patients. Three of these patients had pure spinal SEP
      abnormalities and in the remaining two patients SEPs showed signs of involvement
      of both the spinal and cerebral somatosensory tracts. After treatment, the three
      patients with pure spinal abnormalities showed clinical and neurophysiologic
      worsening, whereas the two patients with a more advanced stage of disease
      (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic
      features. The patients with abnormal brain MRI at the onset of treatment showed
      clinical and neurophysiologic worsening. CONCLUSIONS: Lorenzo's oil therapy had
      no effect on patients with evidence of inflammatory brain lesions. Moreover, in
      patients without clear signs of inflammatory damage, this treatment does not
      modify significantly the natural course of the disease. However, because
      effective treatments should begin before the onset of severe neurologic symptoms,
      SEPs and MEPs should be considered to evaluate the effectiveness of other
      experimental treatments in the patient with a negative brain MRI.

PMID- 10078733
TI  - Kallmann's syndrome: mirror movements associated with bilateral corticospinal
      tract hypertrophy.
AB  - OBJECTIVE: To investigate the etiology of mirror movements in patients with X
      linked Kallmann's syndrome (xKS) through statistical analysis of pooled white
      matter data from structural MR images. BACKGROUND: Mirror movements occur in 85%
      of xKS patients. Previous electrophysiologic studies have suggested an abnormal
      ipsilateral corticospinal tract projection in xKS patients exhibiting mirror
      movements. However, an alternative hypothesis has proposed a functional lack of
      transcallosal inhibitory fibers. METHODS: T1-weighted brain scans were normalized
      into stereotaxic space with segregation of gray and white matter to allow
      comparison of pooled white matter data on a voxel-by-voxel basis using SPM-96
      software. Nine xKS patients were compared with two age-matched groups of
      nonmirroring individuals: nine patients with autosomal Kallmann's syndrome (aKS)
      and nine age-matched normal (healthy) men. RESULTS: Hypertrophy of the corpus
      callosum was found in both Kallmann's syndrome groups: the anterior and
      midsection in xKS, and the genu and posterior section in aKS. Bilateral
      hypertrophy of the corticospinal tract was found only in the group of xKS
      patients exhibiting mirror movements. SPM analysis was validated by an
      independent region of interest analysis of corpus callosum size. CONCLUSION:
      Although morphometry on its own cannot determine the cause of mirror movements,
      the specific finding of a hypertrophied corticospinal tract in xKS is consistent
      with electrophysiologic evidence suggesting that mirror movements in xKS result
      from abnormal development of the ipsilateral corticospinal tract fibers.

PMID- 10078734
TI  - Involuntary movements and abnormal spontaneous EMG activity in syringomyelia and
      syringobulbia.
AB  - OBJECTIVE: To describe different types of involuntary movements and abnormal
      spontaneous electromyographic (EMG) activity in patients with syringomyelia.
      BACKGROUND: A comprehensive study on involuntary movements in patients with
      syringomyelia has not yet been undertaken, to these authors' knowledge. METHODS:
      One hundred adult patients with syringomyelia were examined over the last 15
      years. Involuntary movements were videotaped and evaluated by two independent
      observers. Electromyographic recordings were made using bipolar surface
      electrodes. The H-reflex recovery curve was obtained after stimulation of the
      median nerve at the elbow and recording from the flexor carpi radialis. RESULTS:
      Involuntary movements or abnormal postures were observed in 22 patients. Three
      patients showed segmental spinal myoclonus, nine minipolymyoclonus, and four
      propriospinal myoclonus. Five patients had unilateral or bilateral hand postural
      tremor (8-10 Hz). Focal or segmental dystonia was observed in three patients.
      Electromyography showed spontaneous bursts of grouped action potentials
      synchronous in muscles innervated by the same spinal segment, synchronous firing
      of neurogenic motor unit potentials, or continuous motor unit activity. Increased
      H-reflex responses to conditioning stimuli were found in patients with spinal
      myoclonus. Long latency responses were obtained during peripheral nerve
      stimulation in four patients. Four patients had rigidity and abnormal upper limb
      posture. Respiratory synkinesis was observed in three patients. One patient
      developed inverse masticatory muscle activity. CONCLUSIONS: Patients with
      syringomyelia showed a wide spectrum of involuntary movements. An increased
      excitability of spinal motor neurons was probably the basic underlying mechanism.

PMID- 10078735
TI  - Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive
      changes.
AB  - OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness
      on the excitability of the neuronal circuitry underlying blink reflex, and to
      localize the site of changes in blink reflex excitability that occur after facial
      weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification
      of the blink reflex occurs after facial weakness. Such adaptations generally
      optimize eye closure. A report of blepharospasm following Bell's palsy suggests
      that dysfunctional adaptive changes can also occur. METHODS: Blink reflex
      recovery was evaluated with paired stimulation of the supraorbital nerve at
      different interstimulus intervals. Comparisons were made between normal control
      subjects and patients with Bell's palsy who either recovered facial strength or
      who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in
      patients with residual weakness but not in patients who recovered facial
      strength. Facial muscles on weak and unaffected sides showed enhancement. In
      patients with residual weakness, earlier blink reflex recovery occurred when
      stimulating the supraorbital nerve on the weak side. Sensory thresholds were
      symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on
      ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve
      on the paretic side suggests that sensitization may be lateralized, and suggests
      a role for abnormal afferent input in maintaining sensitization. Interneurons in
      the blink reflex pathway are the best candidates for the locus of this
      plasticity.

PMID- 10078736
TI  - Primary and transitional progressive MS: a clinical and MRI cross-sectional
      study.
AB  - BACKGROUND: Ten percent of patients with MS have a progressive course from onset
      with no history of relapses or remissions. A smaller subgroup follow a similar
      progressive course but have a single relapse at some point (transitional
      progressive [TP] MS). To date these patients have been excluded from receiving
      licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To
      document the clinical and MRI characteristics of a large cohort of progressive
      patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data
      from a small reference group of 20 patients with secondary progressive (SP) MS
      are also presented for reference. METHODS: Patients were recruited from six
      European centers. All underwent a clinical assessment including scoring on the
      Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord.
      RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42%
      men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease
      onset was significantly higher in the PP group than it was in the other two
      groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had
      lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02
      versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP
      cohorts had significantly more T2-weighted lesions in the spinal cord than the PP
      patients, and the SP cohort had the greatest degree of atrophy. There was a
      correlation in the PP and TP patients between EDSS score and brain and spinal
      cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The
      PP and TP patients who presented with spinal cord pathology had significantly
      lower brain T2 and T1 lesion loads than those with non-spinal cord presentations
      (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is
      difficult, although measures of atrophy correlate with the EDSS and appear most
      promising. This study increases our understanding of this unique patient group,
      which will be further expanded with the acquisition of serial data.

PMID- 10078737
TI  - Magnetization transfer imaging of patients with definite MS and negative
      conventional MRI.
AB  - OBJECTIVE: To assess, in a group of patients with clinically or laboratory
      supported definite MS and negative conventional MRI scans of the brain, whether
      magnetization transfer imaging (MTI) is able to detect subtle white matter
      changes. BACKGROUND: MTI of the brain in patients with MS frequently demonstrates
      the presence of microscopic damage to white matter, which appears normal on
      conventional MRI. METHODS: Brain MRI and MTI scans were obtained from 11 patients
      with negative conventional MRIs of the brain, selected from 618 clinically or
      laboratory-supported definite MS cases scanned in the last 2 years in three
      Italian MS centers. RESULTS: Compared with control subjects, patients had
      significantly lower mean MT ratios (MTR) in the pons, cerebellum, and
      periventricular regions. The percentages of pixels with MTR values below 1, 2,
      and 3 SD of the mean MTR value of the control subjects were 7.6% (range, 3.2% to
      11.8%), 5.2% (range, 2.0% to 8.5%), and 3.6% (range, 1.2% to 6.1%), respectively.
      They were mainly located in the white matter of the centra semiovalia, and
      usually were isolated. CONCLUSIONS: MTI can detect white matter abnormalities in
      patients with MS and negative conventional brain MRI scans. The detection of such
      abnormalities may increase diagnostic confidence in those cases where MS is
      clinically suspected, but conventional MRI does not suggest the diagnosis.

PMID- 10078738
TI  - Spinocerebellar ataxia type 6: evidence for a strong founder effect among German
      families.
AB  - The authors found a strong geographic cluster of spinocerebellar ataxia type 6
      (SCA6) families in the Northrhine-Westfalia area, suggesting a founder effect in
      the German SCA6 population. Genotyping with DNA markers linked to the CACNL1A4
      gene on chromosome 19p13 revealed a common haplotype and shared allelic
      characteristics in the majority of German families. The observed founder effect
      may be related to the relative meiotic stability of CAG repeats in this type of
      autosomal dominant cerebellar ataxia.

PMID- 10078739
TI  - A diagnostic protocol for adult-onset glycogen storage disease type II.
AB  - To analyze the diagnostic value of various laboratory tests for the confirmation
      of adult-onset glycogen storage disease type II (GSD II), we performed a
      clinical, biochemical, and genetic study of 18 patients with this disease.
      Measurement of acid alpha-glucosidase (GAA) activity in muscle and
      histopathologic analysis of muscle tissue appeared to have no additional value
      when GAA activity in leukocytes was clearly deficient. Our study showed that
      creatine kinase elevation is a sensitive marker of GSD II. A diagnostic protocol
      is formulated.

PMID- 10078740
TI  - Creatine monohydrate increases strength in patients with neuromuscular disease.
AB  - Creatine monohydrate has been shown to increase strength in studies of young
      healthy subjects and in a few studies with patients. Creatine monohydrate (10 g
      daily for 5 days to 5 g daily for 5 days) was administered to patients with
      neuromuscular disease in a pilot study (Study 1; n = 81), followed by a single
      blinded study (Study 2; n = 21). Body weight, handgrip, dorsiflexion, and knee
      extensor strength were measured before and after treatment. Creatine
      administration increased all measured indices in both studies. Short-term
      creatine monohydrate increased high-intensity strength significantly in patients
      with neuromuscular disease.

PMID- 10078741
TI  - Cerebellar ataxia with glutamic acid decarboxylase autoantibodies.
AB  - Degenerative cerebellar ataxia with autoantibodies against glutamic acid
      decarboxylase (GAD) is a rare disorder and may represent a subset of ataxias
      previously classified as idiopathic. The authors report a patient with
      progressive cerebellar ataxia, insulin-dependent diabetes mellitus, and GAD
      antibodies who responded to i.v. immunoglobulins.

PMID- 10078742
TI  - Acute inflammatory neuropathy in Charcot-Marie-Tooth disease.
AB  - The authors report an association between acute inflammatory neuropathy and
      previously undiagnosed Charcot-Marie-Tooth 1A disease in a 15-year-old girl.
      Sural nerve biopsy study showed hypertrophic neuropathy with endoneurial
      infiltrates of macrophages and lymphocytes. This association may be coincidental,
      but a particular susceptibility to damage of these peripheral nerves cannot be
      excluded. This report confirms the importance of pes cavus as a sign of long
      standing sensorimotor neuropathy.

PMID- 10078743
TI  - Myofibrillar myopathy: no evidence of apoptosis by TUNEL.
AB  - The pathogenesis of myofibrillar myopathy (MFM) is not known. Muscle biopsy
      specimens demonstrate increased expression of cell cycle regulatory proteins as
      well as the ectopic expression of lamin B and nuclear matrix protein in the
      cytoplasm, suggesting the possibility of apoptosis. The authors investigated for
      apoptosis using the TUNEL method in six muscle biopsy specimens from patients
      with MFM. There was no evidence of apoptotic myonuclei in any of the MFM muscle
      biopsies. Further studies regarding the pathogenesis of MFM and the possible role
      of mitotic catastrophe are needed.

PMID- 10078744
TI  - Neuro-ophthalmologic manifestations of a paraneoplastic syndrome and testicular
      carcinoma.
AB  - The authors report two patients with testicular cancer who exhibited supranuclear
      gaze disorders as a manifestation of a paraneoplastic brainstem
      encephalomyelitis. In the first patient, neuro-ophthalmic dysfunction was
      accompanied by a prominent limbic encephalitis whereas in the second patient, an
      unusual, mixed pendular and jerk nystagmus was manifested. Neuroimaging revealed
      an enhancing hypothalamic mass in the first patient and was negative in the
      second. Blood from both patients contained an antibody previously reported in a
      patient with limbic encephalitis and testicular cancer.

PMID- 10078745
TI  - Age-dependent rate of anaplastic transformation in low-grade astrocytoma.
AB  - Age and histologic grade are interrelated characteristics of diffuse fibrillary
      astrocytomas, because the peak age incidence rises with increasing grade. The
      relationship between age and grade may be explained if age determines the rate of
      anaplastic progression in astrocytomas. The authors tested this hypothesis by
      determining the interval between diagnosis of low-grade astrocytoma and
      progression to high-grade astrocytoma in patients of various ages. A two-way
      scatterplot of age at initial diagnosis versus interval to anaplastic progression
      demonstrated a strong negative correlation (n = 24; Pearson correlation
      coefficient = -0.83; Spearman correlation coefficient = -0.79; p < 0.001 for both
      values). It was concluded that the rate of anaplastic progression in low-grade
      astrocytoma is directly correlated with patient age.

PMID- 10078746
TI  - Idiopathic intracranial hypertension: relation of age and obesity in children.
AB  - The relation between obesity and age in children with idiopathic intracranial
      hypertension (pseudotumor cerebri) has remained uncertain. The authors reviewed
      the records of 45 consecutive children with newly diagnosed idiopathic
      intracranial hypertension seen at two medical centers. Forty-three percent of
      patients aged 3 to 11 years were obese, whereas 81% of those in the 12- to 14
      year age group and 91% of those in the 15- to 17-year age group met criteria for
      obesity (p = 0.01). Younger children with idiopathic intracranial hypertension
      are less likely to be obese than are older children or adults.

PMID- 10078747
TI  - Pramipexole in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder
      with no effective treatment. Dopaminergic agents occasionally produce transient
      symptomatic improvement. The authors report the results of pramipexole treatment
      (4.5 mg daily) in six patients with PSP (average disease duration, 4.4 years).
      Patients were treated for 2 months. Patients were evaluated with the Unified
      Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and Schwab and England
      Activities of Daily Living Scale at baseline and 2 months. Pramipexole was not
      efficacious for the symptoms of PSP.

PMID- 10078748
TI  - Short-term versus longer term pimozide therapy in Tourette's syndrome: a
      preliminary study.
AB  - The authors randomized 10 patients (age range, 7 to 13 years) with Tourette's
      syndrome who had achieved a stable level of tic control on open-label pimozide to
      continue on pimozide (n = 6) or be withdrawn from therapy (n = 4) in a double
      blind study. The median time to end point (the time when an increased dose of
      study medication was required to control tics) was 231 days (continued) versus 37
      days (withdrawn), and the survival curves were significantly different (p =
      0.02). Chronic, longer term treatment with pimozide appears to be more effective
      in controlling the course of tics than using the drug acutely to treat an
      exacerbation.

PMID- 10078749
TI  - GCH1 mutation in a patient with adult-onset oromandibular dystonia.
AB  - The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset
      oromandibular dystonia and no obvious family history of dystonia. The patient
      responded positively to treatment with L-dopa. These findings demonstrate that
      GCH1 mutations must be considered even in patients with dystonic symptoms not
      typical of dopa-responsive dystonia.

PMID- 10078750
TI  - Arm levitation in progressive supranuclear palsy.
AB  - Spontaneous arm levitation (SAL) is well-recognized in cortical-basal ganglionic
      degeneration, but not in other neurodegenerative diseases. We report six cases of
      progressive supranuclear palsy (PSP) with SAL. Pathologic examination in four
      revealed the classic features of PSP with additional areas of focal cortical
      degeneration. We conclude that SAL can occur in PSP and its occurrence may be a
      marker of cortical degeneration.

PMID- 10078751
TI  - Thrombotic carotid megabulb: fibromuscular dysplasia, septae, and ischemic
      stroke.
AB  - The proximal internal carotid artery is most commonly spared in cerebral
      fibromuscular dysplasia. The authors report the cases of three young black
      patients with stroke and carotid megabulbs with fibrous components, two of whom
      had superimposed thrombi.

PMID- 10078752
TI  - Bilateral infarction in the territory of the anterior cerebral arteries.
AB  - An elderly hypertensive man had extensive bilateral infarction in the
      distribution of the anterior cerebral arteries. The circle of Willis was fully
      formed, but occlusion of the dominant anterior cerebral artery, aggravated and
      perhaps caused by postlaparotomy hypotension, produced the dramatic lesions,
      causing akinetic mutism. This stroke pattern occurs in various settings and does
      not require an anomalous azygous unilateral supply to both anterior cerebral
      arteries.

PMID- 10078753
TI  - Possible drug-induced thrombocytopenia secondary to tiagabine.

PMID- 10078754
TI  - Treatment of absence status with intravenous valproate.

PMID- 10078755
TI  - Compression of spinal cord and cauda equina in Charcot-Marie-Tooth disease type
      1A.

PMID- 10078756
TI  - Response to cidofovir after failure of antiretroviral therapy alone in AIDS
      associated progressive multifocal leukoencephalopathy.

PMID- 10078757
TI  - Riluzole-induced pancreatitis.

PMID- 10078758
TI  - Dementia with Lewy bodies.

PMID- 10078759
TI  - Limitations of quantitative sensory testing when patients are biased toward a bad
      outcome.

PMID- 10078760
TI  - Limitations of quantitative sensory testing when patients are biased toward a bad
      outcome.

PMID- 10078761
TI  - Limitations of quantitative sensory testing when patients are biased toward a bad
      outcome.

PMID- 10078762
TI  - Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke.

PMID- 10078763
TI  - Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke.

PMID- 10078764
TI  - A phase II study of IV methylprednisolone in secondary progressive MS.

PMID- 10078765
TI  - Extended use of glatiramer acetate (Copaxone) for MS.

PMID- 10078766
TI  - Geschwind and Critchley.

PMID- 10078767
TI  - Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in
      cognition?

PMID- 10078768
TI  - The sensitive practitioner.

PMID- 10078769
TI  - Toward sensitive practice: issues for physical therapists working with survivors
      of childhood sexual abuse.
AB  - BACKGROUND AND PURPOSE: The high rates of prevalence of childhood sexual abuse in
      the United States and Canada suggest that physical therapists work, often
      unknowingly, with adult survivors of childhood sexual abuse. The purposes of this
      qualitative study were to explore the reactions of adult female survivors of
      childhood sexual abuse to physical therapy and to listen to their ideas about how
      practitioners could be more sensitive to their needs. The dynamics and long-term
      sequelae of childhood sexual abuse, as currently understood by mental health
      researchers and as described by the participants, are summarized to provide a
      context for the findings of this study. SUBJECTS AND METHODS: Twenty-seven female
      survivors (aged 19-62 years) participated in semistructured interviews in which
      they described their reactions to physical therapy. RESULTS: Survivors' reactions
      to physical therapy, termed "long-term sequelae of abuse that detract from
      feeling safe in physical therapy," are reported. Participant-identified
      suggestions that could contribute to the sense of safety are shared. CONCLUSIONS
      AND DISCUSSION: Although the physical therapist cannot change the survivor's
      history, an appreciation of issues associated with child sexual abuse
      theoretically can increase clinicians' understanding of survivors' reactions
      during treatment. We believe that attention by the physical therapist to the
      client's sense of safety throughout treatment can maximize the benefits of the
      physical therapy experience for the client who is a survivor.

PMID- 10078770
TI  - Effect of number of home exercises on compliance and performance in adults over
      65 years of age.
AB  - BACKGROUND AND PURPOSE: There is limited research on the effects of the number of
      exercises a person is told to perform on compliance and performance, as defined
      by cueing requirements, correct alignment, and quality of movement. Some studies
      of medication suggest that compliance decreases as the number of medications
      increases. The purpose of this study was to determine whether older adults comply
      and perform better (ie, requiring less cueing, exhibiting correct alignment, and
      exhibiting controlled, coordinated, and continuous movements) when they are asked
      to do 2, 5, or 8 exercises. SUBJECTS: Subjects were 11 women and 4 men, aged 67
      to 82 years (X=72.8), who were living independently in their communities.
      METHODS: Subjects were randomly prescribed 2, 5, or 8 general strengthening home
      exercises. They were instructed on their exercises at an initial session and
      asked to record the number of repetitions performed each day in a self-report
      exercise log. At a return session 7 to 10 days later, subjects were scored on
      their performance of the prescribed exercises using a newly designed assessment
      tool. RESULTS: The group that was prescribed 2 exercises performed better, as
      defined by their performance tool score, than the group that was prescribed 8
      exercises. The group that was prescribed 5 exercises was not different from the
      groups that performed 2 or 8 exercises. No differences were found among groups
      regarding the self-report measurement of compliance. There was a moderate
      correlation between performance scores and the self-report percentage rates.
      CONCLUSION AND DISCUSSION: Subjects who were prescribed 2 exercises performed
      better than subjects who were prescribed 8 exercises. The question of an optimal
      number of exercises to prescribe to elderly people warrants further study.

PMID- 10078771
TI  - The relationship between submaximal activity of the lumbar extensor muscles and
      lumbar posteroanterior stiffness.
AB  - BACKGROUND AND PURPOSE: Some patients with low back pain are thought to have
      increased lumbar posteroanterior (PA) stiffness. Increased activity of the lumbar
      extensors could contribute to this stiffness. This activity may be seen when a PA
      force is applied and is thought to represent much less force than occurs with a
      maximal voluntary contraction (MVC). Although MVCs of the lumbar extensors are
      known to increase lumbar PA stiffness, the effect of small amounts of voluntary
      contraction is not known. In this study, the effect of varying amounts of
      voluntary isometric muscle activity of the lumbar extensors on lumbar PA
      stiffness was examined. SUBJECTS: Twenty subjects without low back pain, aged 26
      to 45 years (X=34, SD=5.6), participated in the study. METHODS: Subjects were
      asked to perform an isometric MVC of their lumbar extensor muscles with their
      pelvis fixed by exerting a force against a steel plate located over their T4
      spinous process. They were then asked to perform contractions generating force
      equivalent to 0%, 10%, 30%, 50%, and 100% of that obtained with an MVC.
      Posteroanterior stiffness at L4 was measured during these contractions. RESULTS:
      A Friedman one-way analysis of variance for repeated measures demonstrated a
      difference in PA stiffness among all levels of muscle activity. CONCLUSION AND
      DISCUSSION: Voluntary contraction of the lumbar extensor muscles will result in
      an increase in lumbar PA stiffness even at low levels of activity.

PMID- 10078772
TI  - Back care instructions in physical therapy: a trend analysis of individualized
      back care programs.
AB  - BACKGROUND AND PURPOSE: The treatment of people with low back pain often includes
      giving a variety of instructions about back care. The objective of our study was
      to explore the content and sequence of these instructions. SUBJECTS: Our database
      contained information on 1,151 therapy sessions for 132 patients who were treated
      by 21 therapists. METHODS: Hierarchical linear modeling was used to establish
      trends in instructions during the course of treatment. Instructions were measured
      by means of a registration form. RESULTS: Pain management instructions were given
      at the start of treatment and then decreased in later sessions. Instructions
      about taking care of the back in daily activities followed the same course.
      Exercise instructions were introduced after the start of treatment and were
      spread evenly across the visits. The number of recommendations about general
      fitness decreased during treatment. CONCLUSION AND DISCUSSION: The majority of
      back care instructions were spread evenly across therapy visits. Relatively
      little variation in instructions among patients was seen, which may indicate a
      lack of individualization of the back care programs.

PMID- 10078773
TI  - Use of computed tomography and plantar pressure measurement for management of
      neuropathic ulcers in patients with diabetes.
AB  - BACKGROUND AND PURPOSE: Total contact casting is effective at healing neuropathic
      ulcers, but patients have a high rate (30%-57%) of ulcer recurrence when they
      resume walking without the cast. The purposes of this case report are to describe
      how data from plantar pressure measurement and spiral x-ray computed tomography
      (SXCT) were used to help manage a patient with recurrent plantar ulcers and to
      discuss potential future benefits of this technology. CASE DESCRIPTION: The
      patient was a 62-year-old man with type 1 diabetes mellitus (DM) of 34 years'
      duration, peripheral neuropathy, and a recurrent plantar ulcer. Although total
      contact casting or relieving weight bearing with crutches apparently allowed the
      ulcer to heal, the ulcer recurred 3 times in an 18-month period. Spiral x-ray
      computed tomography and simultaneous pressure measurement were conducted to
      better understand the mechanism of his ulceration. OUTCOMES: The patient had a
      severe bony deformity that coincided with the location of highest plantar
      pressures (886 kPa). The results of the SXCT and pressure measurement convinced
      the patient to wear his prescribed footwear always, even when getting up in the
      middle of the night. The ulcer healed in 6 weeks, and the patient resumed his
      work, which required standing and walking for 8 to 10 hours a day. DISCUSSION:
      Following intervention, the patient's recurrent ulcer healed and remained healed
      for several months. Future benefits of these methods may include the ability to
      define how structural changes of the foot relate to increased plantar pressures
      and to help design and fabricate optimal orthoses.

PMID- 10078774
TI  - Connective tissues: matrix composition and its relevance to physical therapy.
AB  - In the last 2 decades, the understanding of CT structure and function has
      increased enormously. It is now clear that the cells of the various CTs
      synthesize a variety of ECM components that act not only to underpin the specific
      biomechanical and functional properties of tissues, but also to regulate a
      variety of cellular functions. Importantly for the physical therapist, and as
      discussed above, CTs are responsive to changes in the mechanical environment,
      both naturally occurring and applied. The relative proportions of collagens and
      PGs largely determine the mechanical properties of CTs. The relationship between
      the fibril-forming collagens and PG concentration is reciprocal. Connective
      tissues designed to resist high tensile forces are high in collagen and low in
      total PG content (mostly dermatan sulphate PGs), whereas CTs subjected to
      compressive forces have a greater PG content (mostly chondroitin sulphate PGs).
      Hyaluronan has multiple roles and not only provides tissue hydration and
      facilitation of gliding and sliding movements but also forms an integral
      component of large PG aggregates in pressure-resisting tissues. The smaller
      glycoproteins help to stabilize and link collagens and PGs to the cell surface.
      The result is a complex interacting network of matrix molecules, which determines
      both the mechanical properties and the metabolic responses of tissues. Patients
      with CT problems affecting movement are frequently examined and treated by
      physical therapists. A knowledge of the CT matrix composition and its
      relationship to the biomechanical properties of these tissues, particularly the
      predictable responses to changing mechanical forces, offers an opportunity to
      provide a rational basis for treatments. The complexity of the interplay among
      the components, however, requires that further research be undertaken to
      determine more precisely the effects of treatments on the structure and function
      of CTs.

PMID- 10078775
TI  - Therapeutic strategies targeting proteins that regulate folate and reduced folate
      transport.
AB  - Folate is an essential vitamin which acts as a precursor for cofactors that
      regulate a variety of biochemical reactions. Cellular uptake of endogenous
      folates as well as antifolate agents such as methotrexate may be regulated by two
      independent transport proteins, the folate receptor and the reduced folate
      carrier. This paper reviews the molecular and functional characteristics of these
      transport systems and potential therapeutic approaches exploiting these targets
      in the treatment of cancer. Understanding of the molecular basis and functional
      characteristics of the transport of endogenous folates and folate analogs via the
      folate receptor and the reduced folate carrier has led to the development of
      novel antifolate agents through rational drug design and targeted therapeutic
      approaches for tumors that express or lack the presence of these transport
      proteins. With this knowledge, new and selective treatment will become available
      to more effectively treat patients with a variety of malignancies.

PMID- 10078776
TI  - Clarithromycin: pharmacokinetic and pharmacodynamic interrelationships and dosage
      regimen.
AB  - In the last decade three important pharmacodynamic parameters: T>MIC, Cmax/MIC
      and AUC/MIC, have been shown to correlate well with in-vitro antimicrobial
      efficacy and that found in animal models, differentiating among groups of
      antibiotics with diverse mechanisms of action such as exposure time or
      concentration-dependent effect. The macrolide antimicrobial agents display
      variable concentration-dependent killing, indicating the increasing importance of
      the Cmax parameter. Clarithromycin, whose T>MIC and AUC influence its clinical
      efficacy, is in an intermediate position between its progenitor, erythromycin,
      and the azalides. This paper reviews pharmacokinetic and pharmacodynamic
      characteristics of clarithromycin, examining the potential impact of these
      properties on the dose and the optimal interval between administrations.

PMID- 10078777
TI  - The increase in carbapenem use and emergence of Stenotrophomonas maltophilia as
      an important nosocomial pathogen.
AB  - Carbapenems, being the broadest spectrum antibiotics, may allow those organisms
      intrinsically resistant to these drugs to be involved more frequently in
      nosocomial infections. Imipenem was introduced to the specialized hospital units
      in Kuwait in October, 1992 and meropenem in late 1996. The main objective of this
      study was to observe prospectively whether, under similar laboratory conditions
      for microbial isolation/identification while these drugs are in use in the
      hospital, there is any proportional increase over time in the recovery of
      Stenotrophomonas maltophilia in relation to the number of yearly admissions and
      drug use. In addition, we also looked for categories of patients infected by S.
      maltophilia, type of infection and antibiotic susceptibility. There was an
      increase in the number of S. maltophilia isolates from 1993 to 1997 significantly
      correlated with the increase in year-wise consumption of carbapenems (p<0.004).
      No correlation was observed between yearly number of admissions and both the
      consumption of carbapenems (p>0.51) and isolation of the organism (p>0.59). Most
      isolates were from cancer, burns and cardiac patients. The commonest types of
      infection were wound and septicemia. The organisms were susceptible mostly to
      ciprofloxacin and co-trimoxazole. The study thus indicates that carbapenem use in
      a hospital environment may result in emergence of nosocomial infections due to
      multiresistant S. maltophilia in high risk patients with very limited choice of
      antibiotics for therapy.

PMID- 10078778
TI  - Antifungal activity of voriconazole (UK-109,496), fluconazole and amphotericin B
      against hematogenous Candida krusei infection in neutropenic guinea pig model.
AB  - Voriconazole (UK-109,496) is a new triazole with in vitro activity against a wide
      spectrum of fungi including yeasts intrinsically resistant to fluconazole such as
      Candida krusei. In this study the efficacy of voriconazole was compared to
      amphotericin B and fluconazole in a neutropenic guinea pig model of
      hematogenously disseminated C. krusei infection. In guinea pigs, neutropenia was
      established by using cyclophosphamide (intraperitoneally, i.p., 100 mg/kg on day
      1 and 4), and dexamethasone (orally, 2 mg/kg/day, for 8 days). Neutropenic guinea
      pigs were infected with 0.5 ml of yeast cell suspension (1 x 10(8) CFU)
      intravenously. Challenged animals were treated with antifungals starting 1 h
      postinfection for 7 days. The animals were divided into five groups: untreated
      control, amphotericin B (1 mg/kg i.p. on alternate days), fluconazole (20 mg/kg
      orally twice daily), and voriconazole (two groups: 5 and 10 mg/kg orally twice
      daily) groups. Guinea pigs were sacrificed 1 day after the last treatment. Brain,
      liver, and kidneys were removed and weighed, tissues were homogenized and fungal
      burden determined by serial quantitative counts. Voriconazole at dosages of 5 or
      10 mg/kg b.i.d. was shown to be significantly more efficacious than either
      amphotericin B or fluconazole in eradicating C. krusei from brain, liver and
      kidney tissue. These data indicate that voriconazole could be efficacious for the
      treatment of infections caused by fluconazole-resistant Candida, such as C.
      krusei.

PMID- 10078779
TI  - Influence of fever on cefazolin pharmacokinetics.
AB  - The influence of fever on the pharmacokinetics of cefazolin was investigated in
      patients with acute febrile diseases. Nine patients were included in the study.
      Antibiotic serum concentrations were determined using high performance liquid
      chromatograpy (HPLC). An analog computer and the SIMULINK software package were
      used to identify the pharmacokinetic model and PCNONLIN software package to
      obtain the secondary parameters. In 6 patients a two-compartment pharmacokinetic
      model of cefazolin was observed during fever and after defervescence. In 2
      patients a two-compartment model changed to a one-compartment after
      defervescence, and a one-compartment model was observed in one patient during
      both periods. Cefazolin-treated patients with a two-compartment model (6/9) had
      higher Cmax, mean steady state serum concentrations (Css), and area under the
      plasma concentration-time curve (AUC(0-->infinity)), smaller central compartment
      volume (V1), and lower clearance (Cl) during fever. The varying distribution of
      antibiotics during fever probably reflects different hemodynamic responses to
      fever.

PMID- 10078780
TI  - Elution of vancomycin and tobramycin bonded to vascular grafts.
AB  - The elution of vancomycin and tobramycin from vascular grafts sealed with
      collagen and human blood was studied in vitro. The release of antibiotics was
      measured in three different types of soaked grafts, including grafts soaked with
      antibiotic after being sealed with albumin, those sealed with antibiotic and
      albumin mixture and those impregnated with fresh blood and antibiotic mixture.
      Each antibiotic was tested at two different concentrations, i.e. 5 mg/ml and 10
      mg/ml for vancomycin and 2 mg/ml and 5 mg/ml for tobramycin. The eluted
      antibiotic concentrations were determined by the fluorescence polarization
      immunoassay. Initially large quantities of antibiotics were quickly eluted,
      depending on the amount of antibiotic mixture. A measurable amount of vancomycin
      was released for 3 days. There was no difference between the elution kinetics of
      the two antibiotics from the three different soaked grafts (p>0.05). Antibiotic
      soaked grafts provided zones of inhibition against Staphylococcus aureus on
      Trypticase soy agar plate for up to 24 h. These results suggest that local
      application for 24 h of vancomycin or tobramycin with vascular grafts may be
      effective to prevent graft infection as shown by the fluorescence polarization
      immunoassay.

PMID- 10078781
TI  - Ecological effect of gatifloxacin on the normal human intestinal microflora.
AB  - Gatifloxacin, a new broad-spectrum fluoroquinolone, was given in oral doses of
      400 mg once daily for 10 days to 18 healthy volunteers, in order to study the
      impact on the normal intestinal microflora. Fecal samples were collected prior to
      administration (Day -4 and Day -1), during the administration period (Day 5 and
      10) and after withdrawal of administration (Day 12, 16, 22, 30 and 50). In the
      aerobic intestinal microflora Escherichia coli strains were eliminated or
      strongly suppressed during the administration period and the numbers of
      enterococci decreased significantly while the numbers of staphylococci increased
      at the same time. In the anaerobic microflora the numbers of clostridia and
      fusobacteria decreased significantly during the administration period while no
      other major changes occurred. The microflora was normalized 40 days after the
      administration of gatifloxacin had stopped. No selection or overgrowth of
      resistant bacterial strains or yeasts occurred. The ecological impact of
      gatifloxacin was shown to be selective and similar to that of quinolones like
      ciprofloxacin, levofloxacin and ofloxacin.

PMID- 10078782
TI  - Strategies for cost-containment: once-daily ceftriaxone plus amikacin as empiric
      therapy for febrile granulocytopenic children with cancer.
AB  - Administration of broad-spectrum antibiotics as empiric therapy to febrile
      granulocytopenic patients has become a widely accepted practice. In order to
      evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily
      doses as empiric treatment for febrile granulocytopenic children with cancer, a
      retrospective review (January-December 1996) of all febrile episodes at our
      institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic
      children with cancer were empirically treated with a once-daily ceftriaxone plus
      amikacin combination. 59/101 (59%) patients had absolute granulocyte count lower
      than 100/mm3 at entry; 46 (45%) were affected by solid tumors, 16 (15%) by
      Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow
      transplantation. The ceftriaxone plus amikacin combination was effective in
      72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4).
      We also evaluated the economic advantages of the ceftriaxone plus amikacin once
      daily regimen when compared with another treatment regimen such as ceftazidime
      plus amikacin requiring three daily doses. Compared with the multiple daily dose
      regimen of ceftazidime plus amikacin, there is a cost saving of US $11 (17,500
      Italian liras) and US $66 (105,000 Italian liras) for both 1-day and 6-day
      treatments, respectively, by using the single daily dose regimen of ceftriaxone
      plus amikacin. The potential of ceftriaxone to lower costs in hospitalized
      patients depends upon its comparable efficacy with other extended-spectrum beta
      lactams, in which case it can reduce overall treatment costs because of its once
      daily administration schedule.

PMID- 10078783
TI  - Cytotoxicity and adjuvant activity of cationic photosensitizers in a multidrug
      resistant cell line.
AB  - The toxicities and phototoxicities of methylene blue (MB), toluidine blue O (TBO)
      and Victoria blue BO (VBBO) in a murine mammary tumour cell line (EMT6-S) and a
      multidrug resistant (MDR) sub-line (EMT6-R) were measured and their efficacy
      against the resistant sub-line was compared to that of doxorubicin and cis
      platinum. The MDR cell line was considerably more susceptible to VBBO than to the
      conventional agent doxorubicin. VBBO was also phototoxic whereas illumination did
      not alter the activity of doxorubicin or of cisplatin. Both TBO and MB showed
      limited light activation (2-fold) in both the sensitive and resistant cell lines.
      Pre-treatment with VBBO prior to exposure to doxorubicin caused a two-fold
      increase in doxorubicin toxicity in both cell lines. MB and TBO, however,
      increased doxorubicin toxicity in EMT6-R cells x2 and x3 respectively, but had
      less effect on the sensitive cell line (increase x1.4 and x2 respectively). Thus
      MB and TBO may act on the MDR cell line via a different mechanism to that of
      VBBO.

PMID- 10078784
TI  - Determination of ifosfamide by HPLC using on-line sample preparation.
AB  - The Authors have developed a novel and easily applicable HPLC method for
      ifosfamide (IF) determination. This method involves on-line sample processing and
      its solid-phase extraction by means of an automatic preparator integrated with
      the chromatographic system. The calibration graph of the method is linear in the
      concentration range 6-200 microg/ml; minimum detectable concentration is 6
      microg/ml. This highly accurate and easily reproducible method was used by the
      Authors in the treatment of osteosarcoma with slow infusion of ifosfamide.

PMID- 10078785
TI  - Etoposide, l-leucovorin and fluorouracil (ELF) regimen in metastatic gastric
      cancer: a phase II study.
AB  - The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly
      palliative, therefore regimens with mild toxicity and acceptable activity should
      be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF)
      is suitable chemotherapy in this situation. We have enrolled 33 patients with
      MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute
      i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil
      500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable
      for response, toxicity and survival. Two patients achieved complete response
      (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had
      stabilization of disease (SD) and 12 patients had disease progression (PD). The
      median survival for all patients was 6 months (range, 1 to 40+). ELF was well
      tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In
      conclusion, the ELF regimen in our trial demonstrated, in this kind of patient,
      moderate activity in the absence of relevant toxicity, confirming its suitability
      in patients in generally poor condition.

PMID- 10078786
TI  - AIDS-related cutaneous Kaposi's sarcoma: failure of treatment with human
      chorionic gonadotropin.

PMID- 10078787
TI  - Parents and their child's fever: do as I say, not as I do?

PMID- 10078788
TI  - Saturday night fever? Reasons for referral from health centres to hospitals
      during weekends in Finland.
AB  - OBJECTIVE: We aimed to examine the reasons for referral from health centres to
      hospitals during the weekend in Finland. METHOD: We conducted a survey of all
      referrals from general practice on two weekends (30 November to 6 December 1992
      and 28 November to 4 December 1994) in central and northern Finland, which
      covered 72% of the area of the country and one-third of the population. The
      participants were 178 GPs from public health centres and who made 530 referrals
      during these weekends. The outcome measures were reasons for referrals by ICPC
      codes with respect to the characteristics of patients, GPs and practices.
      RESULTS: During the weekends studied, 530 patients were referred from out-of
      hours work. More male (53%) than female patients (47%) were referred. Out of a
      total of 530 patients, 213 (40%) were referred to surgery, 139 (26%) to internal
      medicine, 48 (9%) paediatric medicine, 32 (6%) to neurology, 28 (5%) to both ear,
      nose and throat (ENT) and psychiatry, 25 (5%) to gynaecology and 18 (4%) to other
      specialities (ophthalmology, lung disease and cancer departments). Fractures
      requiring surgery, angina pectoris for which patients were sent to internal
      medicine and stroke for which patients were sent to other specialities were the
      most commonly reported reasons for referral. Male patients were referred 12 times
      more often than females for arrhythmia (atrial fibrillation or tachyarrhythmia);
      males experienced dislocations eight times more often and fractures three times
      more often than females. CONCLUSION: Our results point out the need to train GPs
      about those complaints that most often require a referral to specialist care
      during the weekend. Future research should focus on those patients who are
      responsible for the huge gender gap of reasons for referral during weekends.

PMID- 10078789
TI  - What parents think of fever.
AB  - OBJECTIVES: We aimed to assess knowledge, perception and management of fever by
      parents. METHODS: We conducted a questionnaire survey among 392 parents of
      children attending locally a paediatric clinic at The Royal Oldham Hospital. The
      main outcome measures were answers to questions covering a variety of aspects of
      the knowledge, perception and management of fever by parents. RESULTS: Almost
      half the parents used a liquid crystal forehead thermometer. Most could not use a
      glass thermometer. Thirty per cent did not know normal body temperature and would
      have treated children with a temperature below 38 degrees C. Sixty-four per cent
      treated fever with both paracetamol and tepid sponging. Most parents awakened
      children at night for antipyretics. Eighty-one per cent thought that untreated
      fever was most likely to cause fits or brain damage and 7% thought it could cause
      death. CONCLUSION: Parents perceive fever as being dangerous. They have a poor
      knowledge and measure it inaccurately. Needless consultations and hospital
      admissions could be avoided by a change in perception.

PMID- 10078790
TI  - Sexual problems: a study of the prevalence and need for health care in the
      general population.
AB  - BACKGROUND: There has been little research carried out on the prevalence and
      types of sexual dysfunction in the general population, although the indications
      are that such problems are relatively common. Most common sexual problems are
      potentially treatable. However GPs have estimated the prevalence of sexual
      problems to be far lower than survey estimates. OBJECTIVE: To provide an estimate
      of the prevalence of sexual problems in the general population, and assess the
      use of and need for professional help for such problems. METHODS: We used an
      anonymous postal questionnaire survey. The study was set in four general
      practices in England*, and the study population was a stratified random sample of
      the adult general population (n = 4000). The subjects were 789 men and 979 women
      who responded to the questionnaire. The main outcome measures were the presence
      and type of current sexual problems in men and women, and the provision and use
      of treatments for sexual problems. RESULTS: A response rate of 44% was obtained.
      The median age of the responders was 50 years. A third of men (34%) and two
      fifths of women (41 %) reported having a current sexual problem. The most common
      problems were erectile dysfunction (n = 170) and premature ejaculation (n = 88)
      in men; in women the most widely reported problems were vaginal dryness (n = 186)
      and infrequent orgasm (n = 166). In men, the proportion of responders reporting
      sexual problems increased with age, but there was no similar trend in women. Of
      those responders who reported a sexual problem, 52% said that they would like to
      receive professional help for this problem, but only one in ten of these people
      (n = 50) had received such help. CONCLUSION: Among responders there was a high
      level of reported sexual problems. The most frequently reported problems (vaginal
      dryness, erectile problems) may be amenable to physical treatment in practice,
      and yet few had sought or received help. However, many said that they would like
      to receive help. These figures suggest that there may be an important burden of
      potentially reversible sexual problems in the general population.

PMID- 10078791
TI  - When do HIV-infected persons start with antiretroviral therapy? A retrospective
      analysis of patients' monitoring and treatment status in general practice, as
      compared with the 1991 Dutch HIV treatment guidelines.
AB  - OBJECTIVE: We aimed to compare, in a sample of Amsterdam general practices, the
      monitoring and treatment status of HIV-infected patients according to the 1991
      Dutch consensus guidelines for antiretroviral treatment of HIV-infection, which
      advise that therapy be started at a peripheral blood CD4+ cell count of < or =
      300 x 10(6)/l in asymptomatic patients, or < or = 400 x 10(6)/l in symptomatic
      patients. METHOD: In 1994, data were collected from the records of all 511 HIV
      infected patients registered in 14 Amsterdam general practices (20 doctors). The
      main outcome measures were the antiretroviral treatment status of all patients
      who were eligible for treatment, and the disease stage and CD4+ cell counts at
      the onset of therapy for patients who started treatment after publication of the
      1991 guidelines. RESULTS: For 472 patients, data were available on CD4+ cell
      measurement status and disease stage. For 15.9% of patients, CD4+ cells had never
      been measured; most of them were asymptomatic. In 84.1 % of patients, CD4+ cells
      had been measured. Of the 8.9% of patients whose results were not known to GPs,
      93% were treated by a specialist and 76% were symptomatic. Of the remaining 355
      (75.2%) patients whose CD4+ count and disease status were known, 201 (56.7%) met
      the guideline criteria for treatment. Of these, 53.7% received treatment, 27.4%
      were never treated and 18.9% had discontinued treatment. Of the 67 patients who
      started treatment after publication of the guidelines, 36.2% of asymptomatic
      patients and 92.8% of symptomatic patients started later than the guidelines
      advised. CONCLUSION: In the population studied, we found a discrepancy between
      the 1991 treatment guidelines and the actual situation. In a substantial
      proportion of eligible patients, antiretroviral treatment was either not
      administered at all or was administered at a (very) late disease stage. This can
      only be attributed to physicians' and/or patients' attitudes towards
      antiretroviral treatment. Other studies confirm that a number of psychological
      factors may influence treatment decisions. The new combination treatment of HIV
      infection requires an early start and compliance with the guidelines. The degree
      to which doctors and patients are willing and able to comply with the guidelines
      is an important factor to be taken into account, both in research and in the
      development of guidelines.

PMID- 10078792
TI  - An analysis of digital rectal examination and serum-prostate-specific antigen in
      the early detection of prostate cancer in general practice.
AB  - BACKGROUND: Prostate cancer is now the commonest cancer in men and the second
      commonest cause of death from cancer. However, general-practice-based research on
      prostate cancer remains scanty. OBJECTIVES: We aimed to examine the acceptability
      of digital rectal examination (DRE) and serum-prostate-specific antigen (PSA) in
      the early detection of prostate cancer in a general practice setting. Another aim
      was to ascertain the incidence of prostate cancer among 50-79-year-old men in the
      solo practice. METHODS: We conducted an opportunistic, prospective, population
      based study involving men with no prior, proven history of prostate cancer.
      RESULTS: A total of 211 (87.6%) out of 241 targeted patients agreed to take part
      in the study. Abnormal DREs were found in 9%, while 9.5% of PSA tests were found
      to be abnormal. One or both tests were abnormal in 29 patients-13.7% of the study
      population. Eleven biopsies were performed during the study, with cancer detected
      in three (27.3%)-1.4% of the total population. Eighteen patients were not
      biopsied either on clinical grounds or by personal choice. CONCLUSIONS: The
      incidence of abnormal DRE and PSA tests was lower than that detected in previous
      hospital or specialist-based studies. Both tests were found to be highly
      acceptable to the population studied. Not all patients with abnormal early
      detection tests need necessarily proceed to further invasive investigations.

PMID- 10078793
TI  - Utility of ultrasound of the upper urinary tract in elderly men with indicators
      of obstructive symptoms or abnormal flow: how often can silent hydronephrosis be
      detected in general practice?
AB  - BACKGROUND AND OBJECTIVE: While the prevalence of hydronephrosis is very low in
      obduction studies, a prevalence of 3-13% is reported for patients with an
      obstruction who are listed for prostatectomy. In order to evaluate the usefulness
      of transabdominal ultrasound in primary care, we determined the occurrence of
      hydronephrosis in males with symptoms of urinary obstruction in a general
      practice setting. METHOD: A micturition questionnaire (a modified Boyarsky) was
      sent to all men of 55 years or more who were registered in 10 general practices
      in Maastricht, and was followed by an examination at their general practice. Men
      with obstructive symptoms and/or with a free-flow abnormality were examined in
      the hospital with transabdominal ultrasound in order to detect dilatation of the
      upper urinary tract. This ultrasound was repeated approximately 15 months later.
      RESULTS: At the first measurement, none of the examined men (n = 178) had
      hydronephrosis, and this was still the case for 94 men 15 months later.
      CONCLUSION: Renal ultrasound is not necessary in general practice for men with
      uncomplicated obstructive complaints.

PMID- 10078794
TI  - Mildly dyskaryotic smear results: does it matter what women know?
AB  - BACKGROUND: As of 1992, all women in the UK who have a first mildly dyskaryotic
      cervical smear are placed under surveillance for 6 months rather than being
      referred for immediate colposcopy. OBJECTIVES: We aimed to explore the
      relationship between anxiety and understanding about mild dyskaryotic, and to
      propose and discuss a method of analysing free text comments written by
      participants in studies based on structured questionnaires. METHODS: The freely
      scripted text of 236 women who had completed a questionnaire as part of a
      randomized controlled trial to assess the impact of an educational package was
      analysed. Randomization group status was concealed. Texts expressing similar
      views were grouped together and categorized. A matrix was drawn up to encompass
      the categories, and the comments were reallocated accordingly. RESULTS:
      Examination of the free text revealed two dimensions, concern and knowledge.
      There were no differences with respect to the apparent level of concern between
      the two randomization groups. However, comments from the intervention group were
      significantly more likely to have been classified as expressing good or vague
      knowledge than those from women in the control group. CONCLUSION: Although the
      educational intervention improved women's knowledge about the meaning of an
      abnormal smear result, this better knowledge was not correlated with less anxiety
      about the result. The free text analysis was a useful supplement to the main
      trial questionnaires. It demonstrated the existence of a range of understanding
      about cervical dyskaryosis, of anxieties relating to the receipt of such a result
      and the degree of interest women showed in acquiring further information.

PMID- 10078795
TI  - Women patients' preferences for female or male GPs.
AB  - OBJECTIVE: We aimed to investigate general preferences to see a male or female GP
      either some or all of the time, and specific preferences to see a female primary
      health care (PHC) worker for individual health issues; to compare these
      preferences with reported consultation behaviour; and to explore women's
      evaluations of the quality of PHC services in relation to their preferences and
      consultation behaviour. METHOD: Results are reported on 881 women aged 16-65
      years who had consulted their GP in the previous 6 months. Logistical regression
      analysis was undertaken to evaluate whether a general preference to see another
      woman is more important than specific women's health issues in determining why
      some women regularly choose to consult a female GP. RESULTS: General preference
      was 2.6 times more important than specific health issues in predicting choice of
      a female GP in a mixed-sex practice. Nearly a half (49.1 %) of women attending
      male-only practices stated that they wanted to see a female GP in at least some
      circumstances, compared with 63.8% of women in mixed-sex practices. In total,
      65.5% of the sample stated that there was at least one specific health issue for
      which they would only want to be seen by a woman PHC worker. The most positive
      evaluations of the quality of GP services were made by women normally seeing a
      male GP in mixed-sex practices and the least positive evaluations were given by
      women in male-only GP practices CONCLUSIONS: In order to meet women's expressed
      preferences, every GP practice should have at least one female GP available at
      least some of the time and every GP practice should employ a female PHC worker.

PMID- 10078796
TI  - Follow-up care in general practice of patients with myocardial infarction or
      angina pectoris: initial results of the SHIP trial. Southampton Heart Integrated
      Care Project.
AB  - OBJECTIVE: We aimed to assess the effectiveness of a nurse-led programme to
      ensure that follow-up care is provided in general practice after hospital
      diagnosis of myocardial infarction (MI) or angina pectoris. METHODS: We conducted
      a randomized controlled trial with stratified random allocation of practices to
      intervention and control groups within all 67 practices in Southampton and South
      West Hampshire, England. The subjects were 422 adult patients with a MI and 175
      patients with a new diagnosis of angina recruited during hospital admission or
      chest pain clinic attendance between April 1995 and September 1996. Intervention
      involved a programme of secondary preventive care led by specialist liaison
      nurses in which we sought to improve communication between hospital and general
      practice and to encourage general practice nurses to provide structured follow
      up. The main outcome measures were: extent of general practice follow-up;
      attendance for cardiac rehabilitation; medication prescribed at hospital
      discharge; self-reported smoking, diet and exercise; and symptoms of chest pain
      and shortness of breath. Follow-ups of 90.1 % of subjects at 1 month and 80.6% at
      4 months were carried out. RESULTS: Median attendance for nurse follow-up in the
      4 months following diagnosis was 3 (IQR 2-5) in intervention practices and 0 (IQR
      0-1) in control practices; the median number of visits to a doctor was the same
      in both groups. At hospital discharge, levels of prescribing of preventive
      medication were low in both intervention and control groups: aspirin 77 versus
      74% (P = 0.32), cholesterol lowering agents 9 versus 10% (P = 0.8). Conversely, 1
      month after diagnosis, the vast majority of patients in both groups reported
      healthy lifestyles: 90 versus 84% reported eating healthy food (P = 0.53); 73
      versus 67% taking regular exercise (P = 0.13); 89 versus 92% not smoking (P =
      0.77). Take up of cardiac rehabilitation was 37% in the intervention group and
      22% in the control group (P = 0.001); the median number of sessions attended was
      also higher (5 versus 3 out of 6). CONCLUSIONS: The intervention of a liaison
      nurse is effective in ensuring that general practice nurses follow-up patients
      after hospital discharge. It does not alter the number of follow-up visits made
      by the patient to the doctor. Levels of prescribing and reported changes in
      behaviour at hospital discharge indicate that the main tasks facing practice
      nurses during follow-up are to help patients to sustain changes in behaviour, to
      encourage doctors to prescribe appropriate medication and to encourage patients
      to adhere to medication while returning to an active life. These are very
      different tasks to those traditionally undertaken by practice nurses in relation
      to primary prevention, where the emphasis has been on identifying risk and
      motivating change. Assessment of the effectiveness of practice nurses in
      undertaking these new tasks requires a longer follow-up.

PMID- 10078797
TI  - Explicit guidelines for qualitative research: a step in the right direction, a
      defence of the 'soft' option, or a form of sociological imperialism?
AB  - Within the context of health service research, qualitative research has sometimes
      been seen as a 'soft' approach, lacking scientific rigour. In order to promote
      the legitimacy of using qualitative methodology in this field, numerous social
      scientists have produced checklists, guidelines or manuals for researchers to
      follow when conducting and writing up qualitative work. However, those working in
      the health service should be aware that social scientists are not all in
      agreement about the way in which qualitative work should be conducted, and they
      should not be discouraged from conducting qualitative research simply because
      they do not possess certain technical skills or extensive training in sociology,
      anthropology or psychology. The proliferation of guidelines and checklists may be
      off-putting to people who want to undertake this sort of research, and they may
      also make it even more difficult for researchers to publish work in medical
      journals. Consequently, the very people who may be in a position to change
      medical practice may never read the results of important qualitative research.

PMID- 10078798
TI  - Effectiveness of brief intervention on non-dependent alcohol drinkers (EBIAL): a
      Spanish multi-centre study.
AB  - OBJECTIVE: The project was designed to compare the effectiveness of brief
      intervention (BI) versus simple advice (SA) in the secondary prevention of
      hazardous alcohol consumption. METHODS: A randomized controlled trial with a 12
      month follow-up was conducted. A total of 74 community-based primary care
      practices (328 physicians) located in 13 Spanish autonomous regions were
      recruited initially. Out of 546 men screened, only 229 were randomized into BI (n
      = 104) and SA (n = 125); 44.6% of practices finalized the study. The
      interventions on the BI group consisted of a 15-minute counselling visit carried
      out by physicians which included: (i) alcohol quantification, (ii) information on
      safe limits, (iii) advice, (iv) drinking limits agreement, (v) self-informative
      booklet with drinking diary record and (vi) unscheduled reinforcement visits. The
      SA group spent 5 minutes which included (i), (ii) and (iii). RESULTS: There were
      no significant differences between both groups at baseline on alcohol use, age,
      socioeconomic status and CAGE score. After the 12-month follow-up there was a
      significant decrease in frequency of excessive drinkers (67% of BI group reached
      targeted consumption, versus 44% of SA; P < 0.001) as well as weekly alcohol
      intake reduction (BI reached 52 versus 32% in SA; P < 0.001). A trend to improve
      outcome with the number of reinforcement visits was found with BI. The only
      predictor of success was the initial alcohol consumption level. CONCLUSIONS:
      Brief intervention is more effective than simple advice to reduce alcohol intake
      on adult men who attend primary care services in Spain.

PMID- 10078799
TI  - Awareness of and attitude of elderly subjects regarding health care and welfare
      in rapidly ageing population in Japan.
AB  - OBJECTIVES: We aimed to obtain information on the degree of knowledge and
      understanding about the current systems of health care and welfare held by the
      elderly, in order to achieve comprehensiveness in family practice. METHOD: We
      conducted a study on the awareness of healthy elderly persons by direct
      interview. The study was carried out in Kuni Village in a remote mountainous
      region in Japan, where the elderly population accounts for 24.8% of the total
      population. The subjects were self-dependent in their daily living activities and
      were aged 65 years and older. RESULTS: The subjects' knowledge of health care and
      welfare systems was generally good, and the degree of their utilization of these
      systems was also good. But 83.3% of those who did not want to utilize the welfare
      system indicated their preference to depend on their family for support.
      CONCLUSION: Family physicians must endeavour to offer comprehensive care to their
      patients by including these systems for rapidly ageing communities.

PMID- 10078800
TI  - House calls in Lebanon: reflections on personal experience.
AB  - BACKGROUND: Home health services play an important role in decreasing hospital
      admissions and physicians' medical house calls play an integral role in home
      health services. There is no national survey of physicians' house call practice
      in the Lebanon. OBJECTIVES: The aim of this study was to provide some information
      about house call practice in the Lebanon. METHOD: Data on patients examined
      during house call visits between 1 January and the end of December 1995 were
      reviewed. RESULTS: During this period, 137 patients were seen at their home.
      Eighty-four patients (62%) were female and 53 patients (38%) were male. Ages
      ranged from 1 to 85 years. The number of cases seen in 1 month averaged 11. The
      diagnosis differed according to the age group of patients examined. Most of the
      house call visits occurred between 6.30 p.m. to 12.00 p.m. (47%). Fifteen
      patients (11%) were admitted to the hospital. CONCLUSION: The rate of cases per
      month was similar to those reported elsewhere. Physicians might feel reluctant to
      conduct house calls out of hours. Our study revealed that the majority of
      patients were seen between 6 p.m. and 12 p.m., and only 6% were seen after 12
      a.m. It is our belief that house calls are an integral part of family practice
      and need to be stressed during the internships of all primary care physicians.

PMID- 10078801
TI  - Restructuring the primary health care services and changing profile of family
      physicians in Turkey.
AB  - A new health-reform process has been initiated by Ministry of Health in Turkey.
      The aim of that reform is to improve the health status of the Turkish population
      and to provide health care to all citizens in an efficient and equitable manner.
      The restructuring of the current health system will allow more funds to be
      allocated to primary and preventive care and will create a managed market for
      secondary and tertiary care. In this article, we review the current and proposed
      primary care services models and the role of family physicians therein.

PMID- 10078802
TI  - A rationale for staged teaching of basic life support.
AB  - Basic life support is a crucial part of the Chain of Survival. Unfortunately,
      however the skill is complex and cannot readily be acquired--let alone retained-
      in the course of a single training session. Although the problem has long been
      recognised, no new strategies have been widely implemented to counter the
      problem. We believe that staged teaching of CPR might provide a solution, and we
      have devised a program to test this new method. It involves three stages of
      instruction that we have called bronze, silver, and gold standards. The bronze
      standard involves opening the airway and providing chest compression without
      active ventilation: this alone may widen the window of opportunity for successful
      defibrillation in adult victims in out-of-hospital cardiac arrest. Ventilation is
      introduced at silver stage using a ratio of 50:5, with emphasis on its value in
      the resuscitation of children being used as motivation to bring people back for a
      second period of instruction. The gold stage teaches conventional CPR. A pilot
      study has been encouraging and a randomized trial on skill acquisition and skill
      retention is planned.

PMID- 10078803
TI  - Seven years' experience with early defibrillation by police and paramedics in an
      emergency medical services system.
AB  - PRIMARY OBJECTIVE: To assess the outcome of patients with out-of-hospital cardiac
      arrest with ventricular fibrillation as the presenting rhythm in an emergency
      medical services system utilizing a combined police/paramedic response to provide
      early defibrillation. MATERIALS AND METHODS: Police and paramedics were
      dispatched from law enforcement and ambulance communications centers,
      respectively. First-arriving personnel delivered initial shocks, all using
      automated external defibrillators. Patients were classified according to response
      to initial shocks: restoration of pulses with shocks only or in need of advanced
      life support, including epinephrine. Discharge survival was defined as return to
      home without disabling neurologic injury. RESULTS: Over the 7-year period of
      study 131 patients presented with ventricular fibrillation: 58 were first treated
      by police and 73 by paramedics. Restoration of pulses with shocks only and
      discharge survival were not different in police and paramedic groups, with
      overall survival of 40% (53 of 131 patients). Among the survivors, 19% (18/95
      patients) obtained a spontaneous circulation only after administration of
      epinephrine and other ALS interventions. CONCLUSION: Both restoration of a
      functional circulation, without need for advanced life support interventions, and
      discharge survival without neurologic disability are very dependent upon the
      rapidity with which defibrillation is accomplished, regardless of who delivers
      the shocks. In addition, a smaller but significant number of patients who require
      ALS interventions, including epinephrine, for restoration of a spontaneous
      circulation survive to discharge. Short time differences, on the order of 1 min,
      are significant determinants of both immediate response to shocks and discharge
      survival.

PMID- 10078804
TI  - A comparative study of the 1992 and 1997 recovery positions for use in the UK.
AB  - In April 1997 the ILCOR Basic Life Support advisory statements were announced in
      conjunction with changes to the recovery position for use in the UK. This study
      compared the new and old positions by using a questionnaire to assess how well
      each position satisfied the ILCOR statements. The study was carried out over six
      different hospital trusts by eight resuscitation training officers. Each tutor
      alternately taught the 1992 or 1997 recommended positions. After the practical
      session each student completed a questionnaire on ease of learning and use of the
      position, as well as other factors such as spinal stability. They were also asked
      to score the position when they were placed in recovery by other students. Their
      competency was assessed using the ALS criteria. Over the duration of the study
      687 forms were suitable for analysis. For every question there was a significant
      trend in favour of the 92 position, with students finding the technique easier to
      learn and use, simpler for positioning for CPR and with less spinal movement
      during rolling. Possible sources of bias such as previous training, tutor or
      staff grade made no statistical difference to the results. When performed
      competently the 1997 position appears to cause less brachial compression, but
      other problems with learning or use of the 97 position outweigh this advantage.
      The 1992 position currently provides the best compromise between ease of use,
      spinal stability and other factors, and better satisfies the ILCOR advisory
      statements.

PMID- 10078805
TI  - Comparing 1997 Resuscitation Council (UK) recovery position with recovery
      position of 1992 European Resuscitation Council guidelines: a user's perspective.
AB  - Both the 1992 and the 1997 recovery positions were demonstrated to 100 employees
      attending for Basic Life Support resuscitation training at a district general
      hospital (Chesterfield and North Derbyshire Royal Hospital NHS Trust). They used
      both positions, experiencing being the first-aider and the casualty and then
      completed a closed questionnaire. The results were evaluated from this 100%
      response. In every aspect the 1992 or 'How' position was preferred both in terms
      of ease of use and comfort during the procedure by the majority of each sample
      group. In every comparison the 1992 position was preferred highly significantly,
      (P < 0.001) using chi-square statistical analysis.

PMID- 10078806
TI  - Jaw lift--a simple and effective method to open the airway in children.
AB  - Assessment of breathing during resuscitation of children is important.
      Misjudgement due to failure to open the airway may lead to mouth-to-mouth
      ventilation in unconscious children who have retained spontaneous breathing
      efforts, and might lead to completely ineffective ventilation with gastric
      distension. The efficiency of the standard head tilt-chin lift manoeuvre (HT-CL)
      and the jaw lift manoeuvre (JL) for opening of the airway in children was
      investigated. Fifty children between 1 and 9 years of age breathing spontaneously
      during deep anaesthesia were studied. Both manoeuvres were randomly performed in
      all children by nurse anaesthetists. The time for opening and the quality of the
      airway was determined by a blind folded anaesthesiologist listening to the
      breathing sounds. The standard HT-CL manoeuvre was insufficient in 12% of the
      children. JL was more effective than HT-CL in opening the airway in unconscious
      children who had retained attempts at spontaneous breathing. The JL manoeuvre
      may, therefore, be recommended in situations when the HT-CL manoeuvre is
      insufficient.

PMID- 10078807
TI  - Effective application of bronchodilator aerosols from metered-dose inhalers (MDI)
      via resuscitator-bag and adapter.
AB  - We developed an adapter enabling the application of therapeutic aerosols from
      metered-dose inhalers (MDI) via a resuscitator bag. This modification permits the
      bag to act as a spacer which is commonly acknowledged to be a means of improving
      the efficiency of inhaled aerosolized drugs by reducing impaction in the upper
      airways and improving the intrapulmonary deposition of particles small enough for
      intraalveolar penetration. The normal function of the resuscitator bag remains
      unchanged enabling use with intubated patients receiving artificial ventilation.
      METHODS: A total of 24 patients receiving a bronchodilator response test were
      treated with 200 microg salbutamol from a MDI combined with either a spacer or
      our bag. Bodyplethysmography and a lung-function-test were performed before and
      after treatment. RESULTS: Both treatments showed a statistically significant
      reduction of airways resistance. However, no significant difference between the
      bag and the spacer could be detected. CONCLUSIONS: We conclude that the modified
      resuscitator-bag is well suited for the inhalative application of drugs by making
      use of the established MDI-spacer principle. Use of our modified bag will offer
      emergency preclinical therapy of bronchospasm for patients in need of rapid
      effective relief who were formerly dependent on intravenous treatment.
      Application in anaesthesia and intensive care also seems possible.

PMID- 10078808
TI  - Efficacy of chest compression-only BLS CPR in the presence of an occluded airway.
AB  - Reluctance of the lay public to perform bystander CPR is becoming an increasingly
      worrisome problem in the USA. Most bystanders who admit such reluctance concede
      that fear of contagious disease from mouth-to-mouth contact is what keeps them
      from performing basic life support. Animal models of prehospital cardiac arrest
      indicates that 24-h survival is essentially as good with chest compression-only
      CPR as with chest compressions and assisted ventilation. This simpler technique
      is an attractive alternative strategy for encouraging more bystander
      participation. Such experimental studies have been criticized as irrelevant
      however secondary to differences between human and porcine airway mechanics. This
      study examined the effect of chest compression-only CPR under the worst possible
      circumstances where the airway was totally occluded. After 6 min of either
      standard CPR including ventilation with a patent airway or chest compressions
      only with a totally occluded airway, no difference in 24 h survival was found
      (10/10 vs. 9/10). As anticipated arterial blood gases were not as good, but
      hemodynamics produced were better with chest compression-only CPR (P < 0.05).
      Chest compression-only CPR, even with a totally occluded airway, is as good as
      standard CPR for successful outcome following 6.5 min of cardiac arrest. Such a
      strategy for the first minutes of cardiac arrest, particularly before
      professional help arrives, has several advantages including increased
      acceptability to the lay public.

PMID- 10078809
TI  - The physiological response to norepinephrine during hypothermia and rewarming.
AB  - Our purpose was to determine if core hypothermia influences physiological
      responses to norepinephrine (NE); and if rewarming reverses these effects.
      Animals were instrumented to measure mean arterial pressure (MAP) and cardiac
      output (CO). Core temperature was manipulated from 37.5 degrees C (normothermia),
      to 30 degrees C (hypothermia) and the back to 37.5 degrees C (rewarming) using an
      external arterial-venous femoral shunt. At each of these temperatures, baseline
      CO and MAP were measured. Norepinephrine (NE) was infused at rates to deliver
      0.2, 1.0, or 5 microg kg(-1) per h. At each dose CO and MAP was measured again.
      Systemic vascular resistance (SVR) was calculated using the formula (SVR =
      (MAP/CO) x 80). Eight animals underwent all three phases of the protocol. The
      response to NE during normothermia was a significant increase in MAP to doses of
      1 microg kg(-1) per min (P < 0.01) and 5 microg kg(-1) per min (P < 0.01) and SVR
      to doses of 1 microg kg(-1) per min (P < 0.01) and 5 microg kg(-1) per min (P <
      0.01). The response to NE during hypothermia was a significant increase in MAP
      only at doses of 1 microg kg(-1) per min (P = 0.03) and 5 microg kg(-1) per min
      (P = 0.01). The response to NE after rewarming was a significant increase in MAP
      only at a dose of 5 microg kg(-1) per min (P = 0.03). This study shows that core
      hypothermia causes a change in physiological response to NE that rewarming does
      not reverse.

PMID- 10078810
TI  - Improved haemodynamics with increased compression-decompression rates during ACD
      CPR in pigs.
AB  - The haemodynamic effects of variations in the compression-decompression
      frequency, 60, 90 and 120 min(-1) during ACD-CPR, were tested in a randomized
      cross-over design during ventricular fibrillation (VF) in 12 anaesthetized pigs
      (17-22 kg) using an automatic hydraulic chest compression-decompression device.
      There were significant increases with increasing frequency for mean (+/- S.D.)
      carotid blood flow (17 +/- 5, 25 +/- 9 and 36 +/- 12 ml min(-1), transit time
      flow probe), cerebral blood flow (17 +/- 7, 30 +/- 17 and 40 +/- 13 ml min(-1)
      100 g(-1), radionuclide microspheres) and mean aortic pressure (34 +/- 8, 37 +/-
      10 and 43 +/- 7 mmHg), respectively. Myocardial blood flow (radionuclide
      microspheres) and diastolic coronary perfusion pressure, CPP, increased
      significantly from 60 to 90 min(-1) with no further significant increase to 120
      min(-1) (28 +/- 13, 46 +/- 23 and 49 +/- 19 ml min(-1) 100 g(-1) and 25 +/- 8, 31
      +/- 11 and 32 +/- 9 mmHg, respectively). Renal and hepatic blood flow also
      increased with increasing rate. No significant differences in the expired CO2
      levels were observed. In conclusion increasing the compression-decompression
      frequency from 60 to 90 and 120 min(-1) improved the haemodynamics during ACD-CPR
      in a pig model with VF.

PMID- 10078811
TI  - Quantitative analysis of synaptophysin immunoreactivity in human neocortex after
      cardiac arrest: confocal laser scanning microscopy study.
AB  - Transient global ischaemia caused by cardiac arrest results in lesions that
      involve all brain structures. The aim of this study was to investigate the
      condition of synapses in patients surviving, but remaining in a persistent
      vegetative state, following resuscitation after cardiac arrest. We performed a
      quantitative analysis of the distribution and density of elements containing a
      synaptic vesicle protein--synaptophysin (p38)--in human neocortex in cases which
      survived for 1 week, 2 months, and 1 year after the cardiac arrest.
      Neurologically healthy cases that died following an accident served as control.
      Dual-channel confocal laser scanning microscopy (CLSM) was used to image p38
      immunoreactivity (IR) and lipofuscin autofluorescence. In control cases no
      statistically significant differences were found for p38-IR between layers II-III
      and V-VII. However, the temporal cortex had a higher density of p38
      immunoreactive structures than the motor cortex. In postischaemic cases a
      reduction in the density of p38-IR elements was apparent, mainly in the frontal
      and motor cortices and less pronounced in the temporal cortex. The least decrease
      compared with controls was observed in the visual cortex. In the 1 week survival
      case, a maximal decrease in p38-IR (35% below control) was found. In this case,
      the number of p38-IR elements per visual field was decreased, and big aggregates
      of p38-IR structures were observed. In general, the amounts of p38-IR structures
      were higher in all of the control cases compared with the postischaemic cases.

PMID- 10078812
TI  - Obstructed venous cranial blood flow caused by tracheal tube fixation.

PMID- 10078813
TI  - A fatal complication of the Seldings technique for cannulation of the femoral
      vein.

PMID- 10078814
TI  - Esophagogastric cancer: the three "R's".

PMID- 10078815
TI  - Will our healthcare system permit paramedical personnel to do endoscopy?

PMID- 10078816
TI  - Biliary pancreatitis: a review. Emphasizing appropriate endoscopic intervention.
AB  - Gallstones are a common cause of acute pancreatitis. This article reviews acute
      biliary pancreatitis and includes natural history, noting the serious nature of
      some cases; pathogenesis, identifying transient obstruction as the primary
      pathogenetic event; diagnosis, including biochemical parameters and imaging;
      assessment of severity, underlining the importance of early prognostic signs,
      organ failure, and local complications; and management. Management is reviewed in
      detail, giving a historical perspective to the role of surgery, highlighting the
      role of endoscopic retrograde cholangiopancreatography and endoscopic
      sphincterotomy and paying particular attention to the four prospective randomized
      clinical trials in suggesting which patients are most likely to benefit from
      early endoscopic evaluation and therapy. Also discussed are additional clinical
      situations related to biliary pancreatitis in which endoscopic retrograde
      cholangiopancreatography and endoscopic sphincterotomy play a role. Finally, a
      suggested endoscopic approach to acute biliary pancreatitis is presented along
      with an algorithm incorporating severity stratification, principles of endoscopic
      intervention, and concepts of sterile and infected pancreatic necrosis.

PMID- 10078817
TI  - Flexible sigmoidoscopy by paramedical personnel.
AB  - Screening sigmoidoscopy is associated with a 45% to 80% reduction in colorectal
      cancer mortality. Although less than 50% of eligible Americans have been screened
      with flexible sigmoidoscopy (FS), the use of this procedure is rising rapidly. By
      the year 2000, as many as 10 million screening FS per year could be performed. To
      accommodate the increased demand, many medical centers have trained paramedical
      personnel (i.e. physician assistants, nurses, and gastroenterology technicians)
      to perform FS. However, as a result of the paucity of research about this
      practice, only physicians receive a professional fee for performing screening FS.
      Many state Boards of Nursing explicitly prohibit registered nurses (RNs) from
      performing this procedure. This review outlines research about the effectiveness
      of paramedical endoscopists, medico-legal and reimbursement issues, and outlines
      a training program in FS for paramedical personnel.

PMID- 10078818
TI  - The future of gastroenterology in the era of managed care.
AB  - Specialty practice in general, and gastroenterology in particular, is undergoing
      significant transformation as we head into the new millennium.
      Gastroenterologists will need to adapt to the continued evolution and
      consolidation of managed care. Among other issues, gastroenterologists will need
      strategies for dealing with pricing pressures, changing technology, increased
      consumerism, a perceived specialist oversupply, and a rapidly aging population.
      These and other developments will drive a myriad of physician responses in an
      effort to confront changing practice realities.

PMID- 10078819
TI  - Long-term outcome of achalasia treatment: the need for closer follow-up.
AB  - Treatment of achalasia includes pneumatic dilation (PD) and surgical myotomy
      (SM). Success rates range from 32% to 98% and are mostly based on symptomatic
      response. Our aims were to determine the long-term outcome of patients treated
      for achalasia and the adequacy of long-term follow-up. Patients treated with PD
      or SM between 1986 and 1990 were contacted by telephone after a minimum of 4
      years after treatment, and asked about symptoms and need for retreatment since
      their discharge from our institution. Symptomatic response was classified as
      excellent/good or fair/poor using the Vantrappen score. Treatment was deemed a
      failure if patients were symptomatic on callback, needed retreatment, technical
      problems occurred during PD, or perforation occurred. Forty-seven PD patients and
      15 SM patients were studied. There were no significant differences in clinical
      parameters between groups. Median time to callback was 82 and 73 months,
      respectively. Failure rates were high, respectively 74% and 67%. Importantly, 38%
      of PD and 33% of SM patients failed to seek help despite symptom recurrence.
      Achalasia treatment failures are higher than anticipated. This may be because of
      the lack of routine follow-up as well as patients' failure to seek help when
      symptoms recur. Achalasia patients need closer follow-up and may benefit from
      early intervention based on objective tests rather than symptoms alone.

PMID- 10078820
TI  - Efficacy of prolonged administration of intravenous erythromycin in an ambulatory
      setting as treatment of severe gastroparesis: one center's experience.
AB  - Intravenous erythromycin is a potent gastric prokinetic with demonstrated
      efficacy in the acute therapy of gastroparesis; long-term oral therapy has been
      limited by tolerance and modest efficacy. Our aim was to review our experience
      with prolonged administration of intravenous erythromycin in an ambulatory
      setting as therapy for severe gastroparesis, refractory to usual dietary and oral
      prokinetic regimens. We conducted a retrospective analysis of patients with
      gastroparesis treated with intravenous erythromycin for at least 1 month.
      Information on demographics; origin of gastroparesis; dosage, duration, and route
      of administration; clinical outcome in the short- and longer-term; and
      complications were determined. Eleven patients received a total of 14 courses of
      intravenous erythromycin for a median of 6.5 months (range, 1 to 19 months) at a
      median dosage of 300 mg/day (range, 150 to 1,000 mg/day). One patient received no
      benefit, two had complete responses, and all others reported some benefit. Two
      had dramatic relapse on cessation of therapy and subsequently improved on its
      resumption. Parenteral nutrition could be discontinued in one of four patients.
      There were four episodes of line sepsis; two required catheter removal. A
      nonocclusive thrombus developed at the site of a central line in one patient.
      Secondary infections or antibiotic resistance were not encountered. Prolonged
      administration of intravenous erythromycin in an ambulatory setting is feasible,
      well tolerated, and effective in patients with severe gastroparesis.

PMID- 10078821
TI  - Ethnic variations in the occurrence of gastroesophageal cancers.
AB  - Cancers of the esophagus, gastroesophageal junction (including the gastric
      cardia), and stomach represent three separate diseases with marked epidemiologic
      variations. The Department of Veterans Affairs computerized database records the
      ethnicity of all hospitalized patients throughout the United States, which
      provides an opportunity to study the influence of ethnicity on cancer rates in a
      uniform health-care system. All hospitalized patients, from 1980 through 1995,
      with a diagnosis of upper gastrointestinal cancer were identified. For each
      ethnic group and cancer type, hospitalization was expressed as an age-adjusted
      proportional rate per 10,000 hospitalizations from all causes. Hospitalization
      with gastric cancer was most frequent among Asians (48.4 per 10,000
      hospitalizations) followed by blacks (33.3), Hispanics (28.7), American Indians
      (20.3), and whites (12.0). Adenocarcinoma of the gastroesophageal junction
      accounted for 5.9 per 10,000 hospitalizations among Asians, 4.5 among whites, and
      4.5 among Hispanics. Gastroesophageal junction cancer was lowest among blacks
      (2.9) and American Indians (2.4). Finally, squamous cell carcinoma of the
      esophagus was frequent among blacks, 68.2 per 10,000, followed by Hispanics
      (36.4) and Asians (27.8), and was low among whites 24.0 and American Indians
      (21.5). Esophageal cancer rates remained stable in all ethnic groups from 1980
      through 1995; gastroesophageal junction cancer rates increased particularly among
      whites, whereas gastric cancer rates declined in whites and blacks but not in
      Hispanics. There were significant ethnic differences in the occurrence of
      gastroesophageal malignancies among US military veterans. Environmental factors
      may explain some of these differences. Differential rates of Helicobacter pylori
      infection with resultant gastric atrophy and reduced acid output led to a greater
      risk for gastric cancer, but a reduced risk for reflux disease and cardiac
      cancer.

PMID- 10078822
TI  - Clinical results and prognostic factors of radiologically node-positive gastric
      carcinoma.
AB  - Lymph node metastasis determined by histologic examination is an important
      prognostic indicator in gastric carcinoma. However, prognostic value of lymph
      node metastasis detected by computed tomography (CT) is unknown. The aim of this
      study was to evaluate clinical results and prognostic factors of patients with
      radiologically node-positive gastric carcinoma. The study included 78 patients
      with primary gastric carcinoma and lymph node metastasis confirmed by CT. The
      level of lymph node metastasis was simply graded as follows: level I included
      perigastric nodes; level II included intermediate nodes along the left gastric,
      common hepatic, and celiac arteries; and level III included distant nodes along
      the hepatoduodenal ligament, pancreas, spleen, and abdominal aorta. Sixty
      patients (79%) had stage IV tumors showing one or more of the following: level
      III lymph node metastasis in 37, pancreatic invasion in 27, peritoneal
      dissemination in 23, and liver metastasis in 19. Overall 1- and 5-year survival
      rates were 29% and 6%, respectively, and the 1-year survival rate was
      significantly influenced by the level of lymph node metastasis on CT (55% for
      level I, 27% for level II, 7% for level III, P < 0.01). In patients with
      gastrectomy, prognostic factors were tumor size (<10 cm versus >10 cm, P < 0.01),
      gross type (localized versus infiltrative, P < 0.01), histologic type (well
      differentiated versus poorly differentiated, P < 0.01), and curability of the
      disease (curative versus noncurative, P < 0.01). Our study indicates that
      prognosis of patients with radiologically node-positive gastric carcinoma is poor
      because of high frequency of extensive tumor spreads. Patients having only
      positive level I nodes on CT are candidates for curative gastrectomy, which may
      offer long-term survival.

PMID- 10078823
TI  - Heterotopic pancreas: a difficult diagnosis.
AB  - Heterotopic pancreas is a rare disease. We evaluated 17 patients treated
      surgically at our hospital. Epigastric pain (77%), abdominal fullness (30%), and
      tarry stools (24%) were the three most frequent symptoms and signs. The lesions
      were diagnosed as gastroduodenal tumors by gastroduodenoscopy (67%) or upper
      gastrointestinal series (71%). Among these, only one gastric submucosal tumor was
      considered to be heterotopic pancreas preoperatively. Three patients were found
      to have gastric tumor by abdominal ultrasound. Computed tomography, small
      intestinal series, barium enema, endoscopic retrograde cholangiopancreatography,
      angiography, and cholescintigraphy did not help in disclosing lesion. In about
      half of the patients, the lesions were located at the stomach. Tumor size varied
      from 1 to 3 cm. Surgical excision relieved symptoms. These findings indicated
      heterotopic pancreas is still a difficult disease for diagnosis, regardless of
      the improvements of diagnostic tools and techniques.

PMID- 10078824
TI  - Factors predicting progression to cirrhosis and hepatocellular carcinoma in
      patients with transfusion-associated hepatitis C virus infection.
AB  - The clinical progression of chronic hepatitis C is not uniform throughout the
      entire period of infection and is more rapid in patients with advanced histologic
      disease. Our study was designed to identify factors contributing to progression
      to cirrhosis and hepatocellular carcinoma by taking the entire period of
      infection into consideration. Two hundred thirteen patients with transfusion
      associated hepatitis type C chronic liver disease were included in this study.
      They did not have either a history of antiviral therapy or any other potential
      causes of chronic liver disease except for transfusion. Hepatitis C virus
      genotype 1b was detected in 144 (68%) patients, followed by 2a in 51 (24%), 2b in
      11 (5%), 1a in 4 (2%), and coinfection with 1b and 2a in 3 (1%). The log-rank
      test in the Kaplan-Meier method revealed that the cumulative percentage of
      cirrhosis-free or hepatocellular carcinoma-free patients became significantly
      lower as the transfusion age went up. Patient age at the time of transfusion was
      the only independent factor related to disease progression in multivariate
      analysis using Cox's proportional hazards model. Thus age at transfusion should
      be taken into consideration in designing the optimal follow-up schedule and
      therapy in patients with posttransfusion-associated chronic hepatitis C.

PMID- 10078825
TI  - Detection of serum p53 antibodies in mucosal colorectal cancer and negative
      conversion after endoscopic resection.

PMID- 10078826
TI  - Gallbladder carcinoma producing alpha-fetoprotein.
AB  - Alpha-feto protein (AFP) is a clinically useful marker for hepatocellular
      carcinoma, hepatoblastoma, and nonseminomatous testicular tumors. Elevated serum
      AFP can also occur with tumors of the gastrointestinal tract, pancreas, lung,
      kidney, and urachus. Serum AFP can also be minimally elevated in nonmalignant
      conditions including acute and chronic hepatitis, cirrhosis, and pregnancy.
      Reports of gallbladder carcinoma that elaborate AFP are extremely rare, and
      almost all represent papillary carcinomas. Until now, there have been only two
      reports in the world literature that describe undifferentiated gallbladder
      carcinoma with elevated serum AFP. The authors present one case of
      undifferentiated gallbladder carcinoma and another case of poorly differentiated
      gallbladder carcinoma with increased serum AFP. In both cases, serum AFP was
      particularly useful in documenting metastatic recurrence of gallbladder
      carcinoma.

PMID- 10078827
TI  - Markedly elevated CA125 in hepatic cirrhosis: two case illustrations and review
      of the literature.
AB  - CA125 is the most widely used tumor marker presently available for use in
      patients with epithelial ovarian cancer. Although elevated in a high percentage
      of patients with ovarian cancer, serum CA125 levels have also been detected in
      patients with numerous benign and malignant nongynecologic disorders, including
      various diseases of the liver. Despite this well-publicized fact, it has become
      apparent that the association between CA125 elevation, particularly the degree of
      elevation, and liver disease may not be as widely recognized as one would
      suspect. When marked CA125 elevations occur, diagnostic confusion is common. We
      describe two cases illustrative of this point. Both cases involve middle-aged
      women who presented with massive ascites and due to markedly elevated serum CA125
      levels underwent exploratory laparotomy with hysterectomy and/or bilateral
      salpingo-oopherectomy before their referral to our center. Because preservation
      of a woman's reproductive organs is a significant concern, it is imperative that
      both primary care physicians and specialists are aware of such associations and
      the proper use of tumor markers.

PMID- 10078828
TI  - Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural
      findings of the liver.
AB  - Two patients with primary amyloidosis (amyloid light chain case) and severe
      cholestatic jaundice are described. Liver biopsy in the preterminal stage
      demonstrated amyloid deposits in the perisinusoidal space and in portal tracts,
      and hepatocytes were atrophic because of compression by amyloid fibrils.
      Ultrastructural findings showed amyloid fibrils not only in Disse's space but
      also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils
      were spicular. There were aggregates of lysosomal granules in the vicinity of
      bile canaliculi and some bile canaliculi were dilated with loss of microvilli.
      Amyloid fibrils in the portal tract compressed bile ductules, causing wide
      intercellular space and separated basement membranes from their epitheliums.
      These findings suggested disturbance in transporting not only of essential
      materials from sinusoids to hepatocytes but also of secretory vesicles into bile
      canaliculi and leakage of bile juice from small bile ductules in preterminal
      stage of primary amyloidosis.

PMID- 10078829
TI  - Primary leiomyosarcoma of the greater omentum.
AB  - We report a case of primary greater omental leiomyosarcoma successfully resected
      by omentectomy. Palpation of a painless abdominal mass at physical examination
      motivated medical imaging examination. Ultrasound visualized accurately the
      internal structure of the lesion but failed to determine the site of origin.
      Computed tomography and angiography determined the greater omental origin of the
      tumor before surgery. A review of the literature is also presented.

PMID- 10078830
TI  - Duodenal ulceration into the cystic artery with massive hemorrhage.
AB  - This is a case presentation of a unique cause of intestinal bleeding. A duodenal
      ulcer eroded into the superficial branch of the cystic artery, causing massive
      intestinal hemorrhage. The patient, a 76-year-old woman, presented with left
      upper abdominal and left back pain secondary to cystic lesions in the pancreas
      body and tail. Stress after operation and complication of leakage of pancreatic
      juice after distal pancreatectomy with splenectomy and diclofenac sodium
      administration may have caused a deep peptic ulcer to erode the cystic artery. We
      performed a transfixing ligation of the bleeding vessel, serosal suture of ulcer
      of the gallbladder, and simple closure of the duodenal ulcer with covering
      greater omentum. There were no serious complications after the operation, and the
      patient made an uneventful recovery.

PMID- 10078831
TI  - A case of acute phlegmonous gastritis successfully treated with antibiotics.
AB  - Acute phlegmonous gastritis is a rare disorder in which bacterial infection
      occurs in the gastric wall. Gastrectomy involving the affected area has been
      thought to be an effective form of treatment. The authors report a case of a 32
      year-old woman who had severe upper abdominal pain without signs of peritoneal
      irritation. Endoscopy showed edematous and reddened gastric mucosa with a mass
      lesion in the gastric antrum. Endoscopic ultrasonography showed thickening of the
      antral wall and a low-echoic mass in the gastric antrum, thought to represent a
      fluid collection. White pus was aspirated from the mass. Localized type of acute
      phlegmonous gastritis with a gastric abscess was diagnosed. Culture of the pus
      showed Streptococcus pneumoniae. Through early diagnosis without laparotomy, the
      patient's gastritis was successfully treated with antibiotics alone.

PMID- 10078832
TI  - Eradication of Helicobacter pylori, improvement of gastritis, and the
      normalization of the hyperproliferative state of gastric mucosa did not prevent a
      case of gastric cancer.

PMID- 10078833
TI  - Lymph node metastasis and level of inferior mesenteric artery ligation in
      colorectal cancer.

PMID- 10078834
TI  - Isoniazid and nonalcoholic steatohepatitis.

PMID- 10078835
TI  - Cocaine packet ingestion.

PMID- 10078836
TI  - Species differences in the hepatic and intestinal metabolism of cyclosporine.
AB  - 1. Cyclosporin A (cyclosporine, CSA) is an immunosuppressive drug with a narrow
      therapeutic index. In the present study the metabolism of CSA was investigated in
      the liver and small intestinal microsomes obtained from rat, hamster, rabbit,
      dog, baboon and man by measuring the disappearance of CSA and the formation of
      the principal metabolites of CSA, namely hydroxylated and N-demethylated CSA. 2.
      CSA was metabolized at a very slow rate (2-8% metabolism in 30 min) in rat liver
      microsomes whereas microsomes from dog livers were very efficient (70-100%
      metabolism in 30 min) in metabolizing CSA. Hydroxylation and N-demethylation
      accounted for most of the CSA metabolized in all the species tested. 3.
      Microsomes from the small intestine produced qualitatively a similar metabolic
      profile as compared with the microsomes from the liver, but at a slower rate in
      all the species tested. The relative importance of the different metabolic
      pathways, however, differed between species. 4. This study points to the
      importance of recognizing the similarities and the differences in the metabolism
      of CSA in different species when data from animal studies are extrapolated to
      man.

PMID- 10078837
TI  - Structural and functional integrity of precision-cut liver slices in xenobiotic
      metabolism: a comparison of the dynamic organ and multiwell plate culture
      procedures.
AB  - 1. Objectives were two-fold: (1) to compare the viability of precision-cut liver
      slices in two culture systems, namely the dynamic organ and the multiwell plate;
      and (2) to evaluate whether increasing the number of slices per incubation
      results in a proportional increase in the extent of metabolism. 2. With both
      culturing systems, the major products of 7-ethoxycoumarin metabolism were the
      sulphate and glucuronide conjugates of 7-hydroxycoumarin with very low levels of
      the free compound. When the multiwell plate procedure was used, metabolism
      increased linearly for at least 10 h, whereas it tended to plateau after 6 h in
      the dynamic organ culture system. At preincubations > 10 h, significantly more
      metabolism of 7-ethoxycoumarin was seen in the slices cultured using the
      multiwell system compared with the dynamic organ system. 3. Morphological
      evaluation employing light and electron microscopy revealed that liver slices
      incubated using the multiwell system were structurally better preserved compared
      with those incubated using the dynamic organ system. 4. Using the multiwell
      system, increasing the number of slices per incubation from one to two resulted
      in only a modest increase in the metabolism of 7-ethoxycoumarin. The rate of
      metabolism of this substrate was much higher with one liver slice when expressed
      per mg homogenate protein. 5. It is concluded that (1) the multiwell plate
      culture system for culturing slices is superior to the dynamic organ system in
      studying the metabolism of xenobiotics following long-term incubations, (2)
      increasing the number of slices per incubation does not result in a corresponding
      increase in the rate of metabolism, and (3) in both culture systems optimal
      viability appears to be within 24 h of incubation.

PMID- 10078838
TI  - Quantitative structure-metabolism relationships (QSMR) using computational
      chemistry: pattern recognition analysis and statistical prediction of phase II
      conjugation reactions of substituted benzoic acids in the rat.
AB  - 1. Quantitative relationships between molecular physico-chemical properties of 22
      substituted benzoic acids and the extent of excretion of their metabolites in rat
      urine have been investigated using computational chemistry and multivariate
      statistics. 2. A data set of 34 theoretically derived physico-chemical
      descriptors calculated was used to classify the benzoic acids according to their
      predominant urinary metabolic fate. 3. Quantitative structure-metabolism
      relationships were obtained by linear regression using combinations of physico
      chemical descriptors allowing the prediction of % urinary excretion of glycine (r
      = 0.73) and glucuronide conjugates (r = 0.82) and % urinary excretion of the
      parent compound (r = 0.91).

PMID- 10078839
TI  - Circadian variation of hepatic glutathione S-transferase activities in the mouse.
AB  - 1. The circadian variation in glutathione S-transferase (GST) activity was
      studied in the hepatic cytosolic fraction of the male and female mouse. A
      circadian variation in GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB)
      was observed in the male, the activity being higher in the light phase (07:00
      19:00 h) than in the dark phase (19:00-07:00 h) during a day under normal
      lighting conditions. 2. The circadian variation was only existed from June to
      October. The difference between the lowest activity (at 01:00 h) and the highest
      activity (at 13:00 h) was maximum in August. 3. In both the normal and reversed
      light/dark cycle (lights on 07:00 and 19:00 h, respectively), reduced glutathione
      (GSH) content was lowest in the middle of the light period and highest in the
      middle of the dark period and GST activity toward 1,2-epoxy-3-(p
      nitrophenoxy)propane (EPNP) exhibited opposite peaks and troughs. GST activities
      toward CDNB and 1,2-dichloro-4-nitrobenzene (DCNB) during the normal lighting
      schedule was higher at 13:00 h than at 01:00 h, but no differences were observed
      under reversed lighting conditions. 4. A circadian variation in GST activity for
      CDNB and DCNB was also observed in the female in a similar manner to the male,
      but the variation in the activity for EPNP was not observed in the female. 5.
      Thus, the circadian variation of hepatic GST activities in mouse were dependent
      on the enzyme substrates used, and seemed to be reflected by the difference in
      each isozyme levels. The daily change in the hepatic GSH levels is also thought
      involved, at least in part, in the regulation of GST activity.

PMID- 10078840
TI  - Fully automated analysis of activities catalysed by the major human liver
      cytochrome P450 (CYP) enzymes: assessment of human CYP inhibition potential.
AB  - 1. Fully automated inhibition screens for the major human hepatic cytochrome
      P450s have been developed and validated. Probe assays were the fluorometric-based
      ethoxyresorufin O-deethylation for CYP1A2 and radiometric analysis of
      erythromycin N-demethylation for CYP3A4, dextromethorphan O-demethylation for
      CYP2D6, naproxen O-demethylation for CYP2C9 and diazepam N-demethylation for
      CYP2C19. For the radiometric assays > 99.7% of 14C-labelled substrate was
      routinely extracted from incubations by solid-phase extraction. 2. Furafylline,
      sulphaphenazole, omeprazole, quinidine and ketoconazole were identified as
      specific markers for the respective CYP1A2 (IC50 = 6 microM), CYP2C9 (0.7
      microM), CYP2C19 (6 microM), CYP2D6 (0.02 microM) and CYP3A4 (0.2 microM)
      inhibition screens. 3. For the radiometric methods, a two-point IC50 estimate was
      validated by correlating the IC50 obtained with a full (seven-point) assay (r2 =
      0.98, p < 0.001). The two-point IC50 estimate is useful for initial screening,
      while the full IC50 method provides more definitive quantitation, where required.
      4. IC50 determined for a series of test compounds in human liver microsomes and
      cytochrome P450 cDNA-expressed enzymes were similar (r2 = 0.89, p < 0.001). In
      particular, the CYP1A2, CYP2D6 and CYP3A4 screens demonstrated the flexibility to
      accept either enzyme source. As a result of incomplete substrate selectivity,
      expressed enzymes were utilized for analysis of CYP2C9 and CYP2C19 inhibition.
      Good agreement was demonstrated between IC50 determined in these assays to IC50
      published by other laboratories using a wide range of analytical techniques,
      which provided confidence in the universality of these inhibition screens. 5.
      These automated screens for initial assessment of P450 inhibition potential allow
      rapid determination of IC50. The radiometric assays are flexible, sensitive,
      robust and free from analytical interference, and they should permit the
      identification and eradication of inhibitory structural motifs within a series of
      potential drug candidates.

PMID- 10078841
TI  - Quantitative studies on the urinary metabolic fate of 2-chloro-4
      trifluoromethylaniline in the rat using 19F-NMR spectroscopy and directly coupled
      HPLC-NMR-MS.
AB  - 1. The metabolism and urinary excretion of 2-chloro-4-trifluoromethylaniline has
      been studied in the rat using 19F-NMR spectroscopy and directly coupled HPLC-NMR
      MS methods. The compound was dosed to three male Sprague-Dawley rats (50 mg kg(
      1) i.p.) and urine collected over 0-8, 8-24 and 24-48 h post-dosing. 2. A total
      urinary recovery of 56.3+/-2.2% of the dose was achieved up to 48 h after dosing.
      The major metabolite in the urine was identified as 2-amino-3-chloro-5
      trifluoromethylphenylsulphate accounting for a total of 33.5+/-2.2% of the dose.
      3. Further metabolites detected and characterized included 2-chloro-4
      trifluoromethylphenylhydroxylamine glucuronide (13.2+/-0.5% of the dose), 2-amino
      3-chloro-5-trifluoromethylphenylglucuronide (3.8+/-0.4% of the dose) and 2-chloro
      4-trifluoromethylaniline-N-glucuronide (3.6+/-0.1% of the dose). Several minor
      metabolites were also found and identified, including 2-chloro-4
      trifluoromethylphenylsulphamate, which together accounted for 2.1+/-0.4% of the
      dose. 4. Directly coupled HPLC-NMR-MS and 19F-NMR spectroscopy is shown to
      provide an efficient approach for the unequivocal and rapid determination of the
      quantitative urinary metabolic fate and excretion balance of a fluorinated
      xenobiotic without the necessity for specific radiolabelling.

PMID- 10078842
TI  - A comparison of 1H8- and 2H8-toluene toxicokinetics in men.
AB  - 1. To examine the bioequivalence of an isotope-labelled tracer to study toxicant
      disposition, we conducted 33 controlled human exposures to a mixture of 50 ppm
      1H8-toluene and 50 ppm 2H8-toluene for 2 h, and measured concentrations in blood
      and breath, and metabolite levels in urine for 100 h post-exposure. 2. A
      physiologically based kinetic (PBK) model found that compared with 1H8-toluene,
      2H8-toluene had a 6.4+/-13% (mean+/-SD) lower AUC, a 6.5+/-13% higher systemic
      clearance (1.46+/-0.27 versus 1.38+/-0.25 l/h-kg), a 17+/-22% larger terminal
      volume of distribution (66.4+/-14 versus 57.2+/-10 l/kg) and a 9.7+/-26% longer
      terminal half-life (38+/-12 versus 34+/-10 h) (p < 0.05 for all comparisons). 3.
      The higher 2H8-toluene clearance may have been due to an increased rate of ring
      oxidation, consistent with the 17% higher observed fraction of 2H5- versus 1H5
      cresol metabolites in urine. 4. The larger terminal volume and half-lives for 2H8
      toluene suggested a higher adipose tissue/blood partition coefficient. 5.
      Observed isotope differences were small compared with interindividual differences
      in 1H8-toluene kinetics from previous studies. 6. The PBK model allowed us to
      ascribe observed isotope differences in solvent toxicokinetics to underlying
      physiologic mechanisms.

PMID- 10078843
TI  - Distribution and heritability of BMI in Finnish adolescents aged 16y and 17y: a
      study of 4884 twins and 2509 singletons.
AB  - OBJECTIVE: 1) To estimate the heritability of body mass index (BMI) in twins aged
      16y and 17y, with a special emphasis on gender-specific genetic effects and 2) to
      compare heights, weights, BMIs, and prevalences of 'overweight' (BMI > or = 25
      kg/m2) in these twins and in singletons aged 16.5y. DESIGN: Cross-sectional and
      longitudinal epidemiological questionnaire study of twins at ages 16y and 17 y,
      and cross-sectional study of singletons at age 16.5y. MEASUREMENTS: BMI (kg/m2)
      was calculated from self-reported heights (m) and weights (kg). SUBJECTS: 4884
      twins (2299 boys, 2585 girls) at baseline (age 16 y), 4401 twins (2002 boys, 2399
      girls) at age 17 y, and 2509 singletons (1147 boys, 1362 girls) at age 16.5 y.
      Both twin and singleton samples are nationally representative. RESULTS: At the
      ages of 16y and 17y, genetic effects accounted for over 80% of the
      interindividual variation of BMI. The correlations for male-female pairs were
      smaller than for either male-male or female-female dizygotic pairs. The
      singletons, especially the boys, had a higher BMI than the twins. Nine percent of
      singleton boys, but only 4-6% of twin boys and twin and singleton girls were
      'overweight' (BMI > or = 25 kg/m2). CONCLUSIONS: Among adolescents, genetic
      factors play a significant role in the causes of variation in BMI. The genetic
      modelling suggested that the sets of genes explaining the variation of BMI may
      differ in males and females. At this age, the twin boys, but not girls, seem to
      be leaner than singletons. Further follow-up will indicate whether these small
      differences disappear, and if not, what implications it might have to the
      generalizability of twin studies.

PMID- 10078844
TI  - Waist and hip circumferences, and waist-hip ratio in 19 populations of the WHO
      MONICA Project.
AB  - OBJECTIVE: To assess differences in waist and hip circumferences and waist-to-hip
      ratio (WHR) measured using a standard protocol among populations with different
      prevalences of overweight. In addition, to quantify the associations of these
      anthropometric measures with age and degree of overweight. DESIGN: Cross
      sectional study of random population samples. SUBJECTS: More than 32000 men and
      women aged 25-64y from 19 (18 in women) populations participating in the second
      MONItoring trends and determinants in CArdiovascular disease (MONICA) survey from
      1987-1992. RESULTS: Age standardized mean waist circumference range between
      populations from 83-98 cm in men and from 78-91cm in women. Mean hip
      circumference ranged from 94-105cm and from 97-108cm in men and women,
      respectively, and mean WHR from 0.87-0.99 and from 0.76-0.84, respectively.
      Together, height, body mass index (BMI), age group and population explained about
      80% of the variance in waist circumference. BMI was the predominant determinant
      (77% in men, 75% women). Similar results were obtained for hip circumference.
      However, height, BMI, age group and population, accounted only for 49% (men) and
      30% (women) the variation in WHR. CONCLUSION: Considerable variation in waist and
      hip circumferences and WHR were observed among the study populations. Waist
      circumference and WHR, both of which are used as indicators of abdominal obesity,
      seem to measure different aspects of the human body: waist circumference reflects
      mainly the degree of overweight whereas WHR does not.

PMID- 10078845
TI  - Age-related changes in fat deposition in mid-thigh muscle in women: relationships
      with metabolic cardiovascular disease risk factors.
AB  - OBJECTIVE: To determine if fat deposition within mid-thigh muscle, represented by
      low density lean tissue density, is associated with age, low physical fitness,
      hyperleptinemia, hyperinsulinemia and dyslipidemia in women. SUBJECTS: Seventy
      two women aged 18-69y with a wide range of total body fat (10-55%) and maximal
      aerobic capacity (VO2max: 17-61 ml/kg(-1)/min(-1)). MEASUREMENTS: Mid-thigh
      muscle, mid-thigh fat, low density lean tissue, intra-abdominal adipose tissue
      (IAAT) and subcutaneous abdominal fat (by computed tomography, CT), fat mass (FM)
      and fat-free mass (FFM) (by dual energy x-ray absorptiometry, DEXA), plasma
      insulin and leptin (by radioimmunoassay, RIA) and lipoprotein lipid profiles (by
      enzymatic methods). RESULTS: VO2max declined with age (r=-0.59, P<0.0001) while
      IAAT and subcutaneous abdominal fat increased with age (r=0.68, r=0.57, r=0.63,
      P<0.0001). Mid-thigh low density lean tissue correlated with age (r=0.52), VO2max
      (r=-0.56), FFM (r=0.35), fat mass (r=0.68), IAAT (r=0.66) and subcutaneous
      abdominal fat (r=0.67, all P<0.005). Mid-thigh low density lean tissue also
      correlated with fasting plasma leptin, insulin, triacylglycerol (TG), total
      cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels (r=0.44,
      0.34, 0.41, 0.50, 0.53, respectively, all P<0.005), but not after controlling for
      body fat and age. Subcutaneous abdominal fat, IAAT, FFM and age were independent
      predictors of low density lean tissue (P<0.05). CONCLUSIONS: Mid-thigh low
      density lean tissue is directly related to age and adiposity. Furthermore, it
      appears that fat accretion in skeletal muscle adversely influences plasma insulin
      and lipoprotein metabolism in women, but not independently of total adiposity and
      age.

PMID- 10078846
TI  - Changes in bioimpedance analysis after stable refeeding of undernourished
      anorexic patients.
AB  - OBJECTIVE: To evaluate bioimpedance analysis (BIA) parameters in patients with
      anorexia nervosa when undernourished and then after stable refeeding. DESIGN:
      Follow-up study. SUBJECTS: Thirteen patients with anorexia nervosa who were
      studied when undernourished (body weight (Wt): 36.9+/-5.6kg, body mass index
      (BMI): 14.8+/-1.8kg/m2) and after stable refeeding (Wt: 52.9+/-7.1kg, BMI: 21.2+/
      2.3 kg/m2) compared to 25 well-nourished control women (Wt: 53.7+/-4.9 kg, BMI:
      21.1+/-1.3 kg/m2). MEASUREMENTS: Impedance and phase angle were determined for
      the whole body (13 patients) and separately for arms and legs (10 patients).
      RESULTS: Bioimpedance index (height2/impedance) and phase angle were lower in the
      undernourished group. Whole-body impedance declined (median, min-max) by 45, 1
      151 Ohm after refeeding; the variations of bioimpedance index (BI-Index) were
      weakly correlated (P < 0.10) with BMI changes. Limb phase angles increased with
      refeeding, but only changes in whole-body phase angle were correlated (P < 0.025)
      with the corresponding variations of Wt or BMI. CONCLUSION: Whole-body phase
      angle increased after weight recovery of anorexic patients, suggesting the
      occurence of modifications in the extracellular-to-intracellular water ratio.
      These changes were proportional to the increase in BMI and Wt.

PMID- 10078847
TI  - Psychosocial and socio-economic factors in women and their relationship to
      obesity and regional body fat distribution.
AB  - BACKGROUND: Abdominal obesity, as well as psychosocial and socio-economic
      handicaps are risk factors for serious, prevalent diseases. Connections between
      these variables have been found in men. OBJECTIVE: The principal aim of the
      present study was to analyse the associations between psychosocial and
      socioeconomic factors with body mass index (BMI) and the waist-to-hip
      circumference ratio (WHR) in women. DESIGN: A cohort study of data derived from
      questionnaires. SUBJECTS: 1137 women from a population sample of 1464 women born
      in 1956. MEASUREMENTS: Occupational, social and leisure time conditions, smoking
      and alcohol habits, as well as height, weight and waist and hip circumferences.
      RESULTS: BMI was associated with teetotalism and negatively to wine drinking. WHR
      correlated directly with cigarette smoking and negatively with consumption of
      wine and beer. Both BMI and WHR, adjusted for each other and for smoking and
      alcohol, showed independent associations with low education, unemployment and
      problems at work when employed, as well as with little physical activity and much
      TV-watching. In addition, the WHR showed a negative, independent relationship to
      housing conditions. CONCLUSION: These observations suggest psychosocial and socio
      economic handicaps as well as a low physical activity in abdominally obese women.
      Similar observations have been made previously in men, but only with the WHR,
      suggesting an influence of obesity in these relationships in women only. Another
      interesting gender difference is the positive relationship between being married
      with BMI in men, as well as being divorced and living alone with the WHR in men
      only.

PMID- 10078848
TI  - Leptin and total cholesterol are predictors of weight gain in pre-pubertal
      children.
AB  - OBJECTIVE: The aim of this study was to identify specifically which biochemical
      indices predict excessive weight gain over time in a cohort of pre-pubertal
      children. SUBJECTS: Fifty nine healthy pre-pubertal children (age: 6.3-9.8y).
      MEASUREMENTS: Children were defined anthropometrically and biochemically at
      baseline. Height and weight measurements were then repeated after six (n=52) and
      12 months (n=37). RESULTS: Weight change after six months (defined by a change in
      body mass index (BMI) z-score from baseline) demonstrated no correlation with
      fasting plasma levels of leptin, insulin, insulin:glucose (IG) ratio,
      cholesterol, triglyceride or high density lipoprotein (HDL) cholesterol. However,
      after 12 months there was a significant negative correlation between BMI z-score
      change and initial plasma leptin (r=-0.35, P=0.048) and this relationship
      strengthened when adjusted for body fat (from bio-electrical impedance; r=-0.46,
      P=0.009). In addition, there was a significant positive relationship between
      plasma total cholesterol and BMI z score change (r=0.38, P=0.03) and this
      relationship remained unchanged when adjusted for body fat. No relationship was
      observed between weight change after 12 months and plasma levels of insulin, IG
      ratio, HDL cholesterol or triglyceride. CONCLUSION: Plasma leptin and total
      cholesterol were found to be predictive of weight gain over 12 months in a cohort
      of pre-pubertal children. These two potential predictors can be readily measured
      in clinical practice and these findings may represent a method of defining the
      'at risk of obesity' state in childhood.

PMID- 10078849
TI  - Regulation of average 24h human plasma leptin level; the influence of exercise
      and physiological changes in energy balance.
AB  - OBJECTIVE: The effects of short-term moderate physiological changes in energy
      flux and energy balance, by exercise and over- or underfeeding, on a 24h plasma
      leptin profile, were investigated. DESIGN: Subjects were studied over 24h in four
      randomized conditions: no exercise/energy balance (energy intake (EI)=energy
      expenditure (EE)=11.8+/-0.8 MJ); exercise/energy balance (EI=EE=15.1+/-0.6 MJ);
      exercise/negative energy balance (EI=11.8+/-0.8 MJ, EE=15.1+/-0.8 MJ);
      exercise/positive energy balance (El=18.6+/-0.7 MJ, EE=15.1+/-0.6 MJ). SUBJECTS:
      Eight healthy, lean men (age: 23.5+/-7.0y, body fat 14.1+/-5.4%, body mass index
      (BMI): 21.4+/-2.3 kg/m2). MEASUREMENTS: Blood was sampled every hour during the
      daytime (09.00-23.00h) and every two hours during the night (01.00-09.00h) for
      analysis of plasma leptin, insulin, glucose, FFA and catecholamines. RESULTS:
      Plasma leptin levels were highest around 01.00h (mean+/-s.e.m. 4.9+/-2.0 ng/ml)
      and lowest around 11.00 h. (2.3+/-0.7 ng/ml). An increased 24h EE, induced by
      exercise under conditions of energy balance, significantly decreased the peak and
      average 24h plasma leptin concentration. A positive energy balance, by
      overfeeding, resulted in a significantly higher amplitude of the 24h plasma
      leptin curve, compared to a condition of energy balance. CONCLUSION: Exercise
      decreases peak and average 24h plasma leptin concentration and a moderately
      positive energy balance increases the amplitude of the 24h plasma leptin profile.
      These effects are not acute, but are manifest within 24h. The variations of
      average 24h FFA and average 24h glucose concentrations almost fully explained the
      variation in average 24h leptin concentration across trials.

PMID- 10078850
TI  - Weights of parents and infants: is there a relationship?
AB  - OBJECTIVE: To assess the relationship between the measures of body weights of
      parents and those of their children during the first two years of life. SUBJECTS:
      Seventy-eight infants born to obese ('high risk') or nonobese ('low risk')
      mothers. METHODS: Weight, weight for length and skinfold thicknesses of the high
      and low risk infants were measured at 3 months, 12 months and 24 months of age. A
      multiple linear regression analysis assessed the contributions of nine risk
      factors, including paternal and maternal body mass index (BMI: kg/m2), to the
      weight and weight for length of infants at 12 months and 24 months of age.
      RESULTS: There were no differences between the high and low risk groups in
      weight, weight for length or skinfold thicknesses at 3 months, 12 months or 24
      months of age. Neither paternal nor maternal BMI entered the multiple regression.
      CONCLUSIONS: These results suggest that genetic influences on the body weight of
      infants may be independent of those that influence BMI in adults, a circumstance
      that could complicate the search for genetic determinants of obesity.

PMID- 10078851
TI  - Absence of genetic variation in some obesity candidate genes (GLP1R, ASIP, MC4R,
      MC5R) among Pima indians.
AB  - OBJECTIVE: To examine the obesity candidate genes glucagon-like-peptide receptor
      (GLP1R), agouti signaling protein (ASIP) and the melanocortin receptors 4 and 5
      (MC4R and MC5R) for DNA polymorphisms in their coding regions. SUBJECTS:
      Unrelated, non-diabetic Pima Indians (8 to 12 from each extreme of body fat).
      MEASUREMENTS: DNA sequencing within the coding regions of each gene. RESULT: Only
      one variant was detected, a silent substitution in exon 6 of GLP1R. CONCLUSION:
      The exclusion of any common amino-acid polymorphisms (allele frequency > or =
      0.20). implies that structural variants of these genes do not contribute to
      variation in the high level of obesity observed among the Pima Indians.

PMID- 10078852
TI  - Black-white differences in social and economic consequences of obesity.
AB  - OBJECTIVE: To investigate social and economic effects of obesity for black and
      white females, and to explore possible explanations for race differences in
      obesity effects. SUBJECTS: 1354 non-Hispanic black and 3097 non-Hispanic, non
      black, women aged 25-33y in 1990 from the National Longitudinal Survey of Youth
      1979-1990. MEASUREMENTS: Body mass index (BMI) evaluated at age 17-24y (1982) and
      25-33y (1990). METHODS: Logistic and linear regression of six labour market and
      marriage outcomes on early or attained BMI. Detailed controls for family
      socioeconomic background. RESULTS: Socioeconomic effects of obesity appear larger
      for whites than blacks. Obesity is associated with low self-esteem among whites,
      but not blacks. Differences in self-esteem do not account for race differences in
      the effects of obesity on socioeconomic status. Lower probability of marriage and
      lower earnings of husbands among those who marry account for the majority of the
      income differences between obese white women and those of recommended weight.
      Occupational differences account for more than one fifth of the effect of obesity
      on the hourly wages of both white and black women. CONCLUSION: Cultural
      differences may protect black women from the self-esteem loss associated with
      obesity for whites. However, differences in self-esteem do not account for the
      effects of obesity on socioeconomic status. Because the effect of obesity on the
      economic status of white women works primarily through marriage, it may therefore
      be less amenable to policy intervention to improve the labor market prospects of
      obese women.

PMID- 10078853
TI  - Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat
      diet.
AB  - OBJECTIVE: Chitin and chitosan are polymers containing more than 5000
      acetylglucosamine and glucosamine units, respectively, and their molecular
      weights are over one million Daltons. The present study assessed the effects of
      chitin-chitosan on the activity of pancreatic lipase in vitro and on the degree
      of fat storage induced in mice by the oral administration of a high-fat diet for
      nine weeks. DESIGN: Mice were fed a high-fat diet and treated with chitin
      chitosan for nine weeks. Experiments were also carried out to clarify whether or
      not chitin-chitosan inhibited pancreatic lipase activity in assay systems using
      triolein emulsified with lecithin, gum arabic or Triton X-100. RESULTS: Chitin
      chitosan prevented the increase of body weight, hyperlipidaemia and fatty liver
      induced by a high-fat diet. Chitin-chitosan inhibited hydrolysis of triolein,
      emulsified with phosphatidylcholine, but not that of triolein emulsified with gum
      arabic and Triton X-100. These results suggest that the site of inhibitory action
      of chitin-chitosan may not be the enzyme but its substrate. CONCLUSION: The anti
      obesity effects of chitin-chitosan in high-fat diet-treated mice might be partly
      due to the inhibition of intestinal absorption of dietary fat. Consequently,
      chitin-chitosan might cause improvement of the fatty liver and hyperlipidaemia in
      mice fed a high fat diet through inhibiting intestinal absorption of dietary fat.

PMID- 10078854
TI  - Relationship of low-density lipoprotein particle size and measures of adiposity.
AB  - OBJECTIVE: To determine if obesity measures are related to measures of low
      density lipoprotein (LDL) size and LDL subfractions in a population of Mexican
      Americans with high prevalence of obesity. METHODS: LDL size phenotypes, based on
      nondenaturing gradient gel electrophoresis and staining for cholesterol (using
      Sudan black B), were determined for 313 unrelated Mexican-American participants
      in the San Antonio Family Heart Study. LDL size measures included predominant
      particle diameter, median diameter (particle diameter, where half the LDL
      absorbance is on larger and half on smaller LDLs) and cholesterol level in
      various LDL subfractions. Adiposity traits included two measures of general body
      fatness (body-mass index (BMI) and fat mass determined with bioimpedance) and
      three measures of regional fat deposition (waist-to-hip ratio (WHR), waist
      circumference and subscapular-triceps skinfold ratio (STR)). RESULTS: Gender and
      diabetes were significantly associated with most LDL size measures. In addition,
      BMI, WHR, waist circumference and STR were significantly (P<0.05) associated with
      several LDL size measures. Stepwise regression analysis (including adjustment for
      age, gender and diabetes status) showed that in every case, the strongest
      adiposity correlate of LDL size, was WHR, which reflects deposition of visceral
      fat. If triglyceride (TG) concentration was also included in the models, no fat
      measure was independently correlated with LDL size, suggesting that elevation of
      TG, associated with increased adiposity, was more directly correlated with LDL
      size. Supporting this interpretation, we found that WHR was also the strongest
      correlate of TG among adiposity measures. Regression analysis of the LDL particle
      size cholesterol profile expressed in 0.1 nm increments revealed a positive
      correlation of WHR and LDLs in the interval 25.9-26.3 nm (P < 0.05) and a
      negative correlation of BMI with LDLs in the interval 27.3-28.1 nm (P < 0.05).
      CONCLUSION: These results suggest that different adiposity measures, reflecting
      different aspects of fat deposition, are related to specific LDL size intervals.
      We speculate that increased deposition of fat, particularly visceral fat, is
      associated with increased TG, which in turn is associated with decreases in LDL
      particle size.

PMID- 10078855
TI  - Effects on body weight of strict or liberal adherence to an initial period of
      VLCD treatment. A randomised, one-year clinical trial of obese subjects.
AB  - OBJECTIVES: To examine the impact on early and late weight loss of three
      different, initial very low calorie diet (VLCD) approaches in a one-year obesity
      treatment program. DESIGN: Randomised clinical trial. SUBJECTS: 121 obese
      subjects, aged 21-60y, BMI > or = 30.0kg/m2. INTERVENTIONS: The VLCD-strict group
      was prescribed a strict outpatient VLCD for 16 weeks, followed by a 36-week
      hypocaloric diet. The VLCD-mw group received the same treatment, but were
      hospitalised in a metabolic ward for the initial week. The VLCD-plus group was
      allowed two small meals weekly, but received otherwise the same recommendations
      as the VLCD-strict group. RESULTS: After 16 weeks, there was no difference in
      weight loss between the treatment groups in the intent-to-treat population, while
      among completers, the weight loss was about 7 kg larger in the VLCD-strict group
      compared to the VLCD-plus group (P < 0.05). At one year, these groups differed by
      approximately 4 kg, both according to intention-to-treat and among completers (P
      < 0.05, both differences). These differences were more prominent among females.
      The weight reduction in the VLCD-mw group was generally not superior to the VLCD
      strict group. CONCLUSIONS: In the short-term, strict VLCD only reduced weight
      better than a liberal VLCD approach among completers. However, after one year, a
      strict VLCD regimen seemed beneficial compared to a liberal VLCD for all
      patients. There was no extra weight loss if the VLCD period was initiated on a
      metabolic ward.

PMID- 10078856
TI  - Spectral analysis of heart rate variability and pulmonary responses to topical
      applications of 2% aminophylline-based thigh cream.
AB  - OBJECTIVE: Noninvasive assessment of the immediate and delayed cardiopulmonary
      response to a 2% aminophylline-based topical thigh reducing cream. DESIGN:
      Prospective, double-blind, randomized, counterbalanced study with application of:
      no cream (NC), placebo cream (PC) or 2% aminophylline cream (AC). SUBJECTS: Nine
      healthy women (aged: 23+/-3 y; weight: 58+/-3 kg; height: 165+/-7 cm; body fat:
      19+/-6%; estimated maximal aerobic fitness VO2max): 40+/-4 ml/kg/min).
      MEASUREMENTS: Medical history, skin patch test, skinfolds, YMCA submaximal cycle
      ergometry test, psychological evaluations (POMS and Speilberger STAI-1).
      Pulmonary function and spectral analysis on heart rate variability, measured
      immediately post-and 4 h post-treatment, on three separate days within a three
      week period. RESULTS: Pulmonary function did not change. The averaged R-R
      interval (ms) was significantly lower for the immediate post AC treatment, but
      returned to baseline in 4 h. CONCLUSION: Application of a 2% aminophylline-based
      thigh cream does not affect pulmonary function, however, it may cause a
      temporary, transient reduction in the averaged R-R interval.

PMID- 10078857
TI  - Eating control and physical activity as determinants of short-term weight
      maintenance after a very-low-calorie diet among obese women.
AB  - OBJECTIVE: To test the hypothesis that eating control and physical activity help
      maintain weight and waist circumference after a very-low-calorie diet. DESIGN: A
      12 week weight reduction (WR) phase, followed by a 40 week weight maintenance
      (WM) phase. For the latter, the subjects were randomised into a no-exercise group
      and one of two groups with a walking program. SUBJECTS: Eighty-five obese (body
      mass index 29-46, mean 34), clinically healthy, premenopausal women.
      MEASUREMENTS: Body weight, waist circumference, body composition, the measuring
      restrained eating, disinhibition and hunger, measured by Three Factor Eating
      Questionnaire (TFEQ), binge eating measured by the Bulimic Investigatory Test of
      Edinburgh (BITE), and number of daily steps measured by a pedometer. RESULTS: The
      change (delta) in weight during WM was predicted by the following regression:
      deltaweight (kg)=5.23+0.45 deltaweight during WR+0.66 disinhibition during
      WM0.00039 daily steps during WM, r2=0.46, SEE 3.3 kg. The change in waist
      circumference during WM was predicted as deltawaist (cm)=0.76+0.75 deltaweight
      during WM0.00021 daily steps during WM, r2=0.67, SEE 2.6 cm. Exercise group
      assignment did not affect the changes in weight, waist circumference, or
      indicators of eating control during the maintenance program. CONCLUSIONS: Control
      of overeating, as indicated by a lower disinhibition factor of the TFEQ, and
      daily physical activity, as indicated by a higher number of daily steps, were
      positive and independent predictors of weight maintenance after a very-low
      calorie diet. The number of daily steps showed an independent association with
      change in waist circumference during weight maintenance, even after adjustment
      for weight change.

PMID- 10078858
TI  - Gallstone disease risk in relation to body mass index and waist-to-hip ratio in
      Japanese men.
AB  - OBJECTIVE: To examine the relation of body mass index (BMI) and waist-to-hip
      ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese
      men. DESIGN: Cross-sectional study. SUBJECTS: We used 174 men with prevalent
      gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the
      consecutive series of 7637 men aged 48-59y receiving a preretirement health
      examination at four hospitals of the Japan Self-Defense Forces between 1986 and
      1994. MEASUREMENTS: Gallbladder status was assessed by abdominal ultrasonography
      after an overnight fast. BMI was calculated as weight in kilogram divided by
      height in square meters, and WHR was used as a measure of central obesity.
      Analysis of the WHR was limited to a subset of data for the period 1991-1994
      (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410). RESULTS:
      After adjustment for hospital, rank in the Self-Defense Forces, cigarette
      smoking, alcohol use and glucose tolerance, BMI was significantly associated with
      an increased risk of both prevalent gallstones and postcholecystectomy. WHR also
      showed a significant positive association with each of the two conditions. When
      BMI and WHR were mutually adjusted for, both of the obesity indices tended to be
      associated positively with prevalent gallstones and postcholecystectomy.
      CONCLUSION: These findings indicate that obesity is associated with increased
      gallstone risk in men.

PMID- 10078859
TI  - Assessment of obesity in a community sample of prepubertal children.
AB  - The aims of this study were to quantify the effect of obesity definition on
      estimates of prevalence, and to determine the sensitivity and specificity of
      three commonly used definitions of overweight/obesity in children: body mass
      index (BMI) s.d. score > 2.00; BMI s.d. score > 1.04; weight > 120% ideal. A
      representative community sample of children in Edinburgh, Scotland (n=240, 124
      boys and 116 girls; mean age 8.5 s.d. 0.4y) was recruited. Obesity was defined by
      a criterion method based on % body fat: > 25% fat in boys; > 32% fat in girls.
      Sensitivity of BMI s.d. score > 2.00 was relatively poor in both sexes (60% in
      girls; 36% in boys) but had high specificity (98%). Sensitivity of the other two
      clinical definitions was higher, and was better in girls than boys, but with
      lower specificity. Choice of definition had a profound effect on prevalence
      estimates. In conclusion, sensitivity of the definitions of obesity currently
      recommended for children, when tested in this sample, was heavily dependent on
      the definition used and differed between boys and girls. This should be
      considered when choosing a definition of obesity in clinical practice and
      epidemiology.

PMID- 10078860
TI  - Diet and snake venom evolution: can local selection alone explain intraspecific
      venom variation?

PMID- 10078862
TI  - Application of immunoaffinity chromatography for detection of tetrodotoxin from
      urine samples of poisoned patients.
AB  - Immunoaffinity chromatography using the monoclonal antibody (Tl-1) specific for
      tetrodotoxin (TTX) has been developed for isolating TTX from urine samples. By
      combining immunoaffinity chromatography with fluorometric high performance liquid
      chromatography (HPLC), it has become possible to detect a small amount of TTX in
      urine samples. The detection limit of TTX in urine was 2 ng/ml. By this combined
      method, TTX was detected in all the urine samples that were collected from
      poisoned patients during the week following TTX ingestion. The combination of
      immunoaffinity chromatography with HPLC was very useful in detecting TTX from the
      urine samples of poisoned patients for diagnosis of TTX-food poisoning.

PMID- 10078863
TI  - The cDNA sequence of an excitatory insect selective neurotoxin from the scorpion
      Buthus martensi Karsch.
AB  - The full-length cDNA of an excitatory insect selective neurotoxin was amplified
      from total cDNAs of venomous glands of the scorpion Buthus martensi Karsch (BmK)
      using the 3'RACE and 5'RACE (rapid amplification of cDNA ends, RACE) method and
      sequenced. The cDNA encoded a precursor of the insect toxin of 88 amino acid
      residues, including a signal peptide of 18 residues and a mature toxin of 70
      residues. The cDNA deduced sequence of this toxin was homologous with the
      determined amino acid sequence of BmK IT1, an excitatory insect toxin purified
      from the scorpion venom, except for three different residues, two at the
      positions 24-25, and another in the COOH-terminus of the toxin. Among them the
      COO-terminal residue Gly in the cDNA deduced sequence was predominantly different
      from the conserved residue Asn found in other known scorpion excitatory insect
      toxins.

PMID- 10078864
TI  - Efficient isolation of the rare diarrhoeic shellfish toxin, dinophysistoxin-2,
      from marine phytoplankton.
AB  - The rare diarrhoeic shellfish poisoning (DSP) toxin, dinophysistoxin-2 (DTX-2),
      which is an okadaic acid (OA) isomer, has been isolated from a marine
      phytoplankton biomass that consisted mainly of Dinophysis acuta. Using a large
      double plankton net (length 5.9 m), bulk phytoplankton samples were collected off
      the south-west coast of Ireland and extracted with methanol and chloroform.
      Liquid chromatography coupled with ionspray mass spectrometry and tandem mass
      spectrometry (LC-MS, LC-MS-MS) showed the sample contained DTX-2 and OA, at a
      concentration of 80 pg/cell and 60 pg/cell, respectively. Flash chromatography
      using silica, sephadex LH20 and C18-silica, followed by preparative reversed
      phase LC, separated DTX-2 from OA. The efficiency of the separation procedures
      was substantially improved by the use of a bioscreen to detect DSP toxins in
      eluate fractions and the application of a new derivatisation procedure for the
      chromatographic elucidation of toxin profiles with fluorimetric detection (LC
      FLD). Thus, 1/1000th aliquots of eluate fractions were assayed using protein
      phosphatase-2A for the presence of inhibitory compounds. Positive fractions were
      further analysed for DSP toxins by LC-FLD following derivatisation using the
      hydrazine reagent, luminarine-3. The identity and purity of the free isolated DTX
      2 was confirmed using flow injection analysis (FIA) and liquid chromatography
      (FIA-MS, LC-MS and LC-MS-MS).

PMID- 10078865
TI  - Modulation of a calcium-activated chloride current by Maitotoxin.
AB  - The effect of Maitotoxin (MTX) on the calcium-activated chloride current (ICl-Ca)
      from Xenopus oocytes was studied, applying the two-electrode voltage clamp
      technique. MTX increased the current amplitude at all the voltages explored and
      reduced the time to reach the maximum current level (time to peak). At low toxin
      concentrations (15 pM), both effects were fully reversible. Activation of ICl-Ca
      by MTX was secondary to the increment in the intracellular Ca2+ concentration
      induced by this toxin, since incubation of the oocytes with the cell-permeant
      Ca2+ chelator BAPTA-AM, greatly reduced the effect of MTX on ICl-Ca. Furthermore,
      external chloride ions removal also diminished the MTX effect on the current,
      strongly suggesting that the main current activated by MTX is ICl-Ca. Subsequent
      applications of a fixed toxin concentration after toxin washout resulted in
      enhanced ICl-Ca, suggesting that the toxin effect potentiates.

PMID- 10078866
TI  - Structure of a Lys49-phospholipase A2 homologue isolated from the venom of
      Bothrops nummifer (jumping viper).
AB  - Lys49-Phospholipase A2 (Lys49-PLA2) homologues damage membranes by a Ca2+
      independent mechanism which does not involve catalytic activity. We have solved
      the structure of myotoxin-I, a Lys49-PLA2 homologue isolated from the venom of
      Bothrops nummifer (jumping viper) at 2.4 A resolution using molecular replacement
      techniques. The final model has been refined to a final R-factor of 18.4% (R-free
      = 23.2%), and shows excellent geometry. The myotoxin-I from Bothrops nummifer is
      dimeric in the crystalline state as has been observed for other Lys49-PLA2
      homologues. In addition, a continuous electron density in the active site and
      substrate binding channel could be successfully modeled as a fatty-acid molecule.

PMID- 10078868
TI  - Bibliography of toxinology.

PMID- 10078867
TI  - Peroxisomicine A1 (plant toxin-514) affects normal peroxisome assembly in the
      yeast Hansenula polymorpha.
AB  - Previously we demonstrated that peroxisomicine A1 (T-514), a plant toxin isolated
      from Karwinskia species, has a deteriorating effect on the integrity of
      peroxisomes of methylotrophic yeasts. Here we describe two strains of Hansenula
      polymorpha, affected in the normal utilization of methanol as sole source of
      carbon and energy due to peroxisomicine A1 treatment. The two strains isolated
      (L17 and RV31) grew poorly on methanol, apparently due to malfunctioning of their
      peroxisomes. Moreover, the cells displayed a high peroxisome turnover rate. We
      argue that the peroxisomicine A1 induced phenotype of both strains is due to a
      genomic mutation. Strain L17 was functionally complemented after transformation
      with a H. polymorpha genomic library. The complementing 2.8 kb DNA fragment did
      not contain a well-defined ORF and led us to speculate that it may contain
      regulatory sequences that, when present in multiple copies in the cell, result in
      a change of expression of specific genes, thus causing restoration of normal
      methylotrophic growth.

PMID- 10078869
TI  - Effect of salt concentration and pH on the hydrophobicity parameters of
      surfactants studied by TLC and spectral mapping technique.
AB  - The lipophilicity and specific hydrophobic area of 56 surfactants having
      different hydrophobic moiety and different length of ethylene oxide chain were
      determined by reversed-phase thin-layer chromatography and the strength and
      selectivity of the effect of sodium chloride and pH on the hydrophobicity
      parameters was elucidated using spectral mapping technique followed by two
      dimensional nonlinear mapping. In each instance significant linear correlations
      were found between the lipophilicity and specific hydrophobic surface area of
      surfactants suggesting that from a chromatographic point of view they behave as a
      homologous series of solutes. It was established that the strength of the effect
      of both salt concentration and pH is relatively low and the selectivity of their
      influence on the hydrophobicity parameters is markedly different.

PMID- 10078870
TI  - N-hydroxysuccinimide carbonates and carbamates are useful reactive reagents for
      coupling ligands to lysines on proteins.
AB  - Ligands containing amino or hydroxyl groups were converted to their corresponding
      activated N-hydroxysuccinimidyl carbamate and carbonate by reaction with
      disuccinimidyl carbonate (DSC). The latter reagents can be used for the group
      specific modification of primary amines as an alternative to the widespread usage
      of N-hydroxysuccinimide esters. Biotin and 2,4-dinitrophenyl (DNP) derivatives
      were used as examples to demonstrate the approach. Biotin and DNP were each
      extended by attaching two different spacer arms, carrying either a hydroxyl group
      or a primary amine as terminal functions. The latter were then activated via
      their conversion to N-hydroxysuccinimide carbonates and carbamates, respectively.
      The usefulness of these reagents for protein modification was investigated. The
      modified proteins obtained exhibited similar stability and activity
      characteristics compared to those modified with active N-hydroxysuccinimdyl
      esters. The activation of hydroxy- or amino-terminating compounds with DSC
      represents a general method that can be applied to any ligand which contains
      these functional groups for its covalent coupling to amines.

PMID- 10078871
TI  - Dual fluorophore-nitroxide probes for analysis of vitamin C in biological
      liquids.
AB  - A new method for quantitative analysis of vitamin C in biological and chemical
      liquids was proposed. The method is based on the use of dual molecule consisting
      of a fluorescent chromophore and a nitroxide radical. In the dual molecule, the
      nitroxide acts as a quencher of the fluorescence of the chromophore fragment.
      Reduction of the nitroxide fragment by ascorbic acid results in decay of ESR
      signal and enhancement of the fluorescence. By performing the series of pseudo
      first-order reactions between the dual molecule and ascorbic acid and consequent
      plotting rate constants versus ascorbic acid concentrations the calibration
      curves for the vitamin C analysis were obtained. Variations of chemical structure
      of fluorophore and nitroxide fragments allow to regulate fluorescent properties
      and redox potentials of the dual molecules. The proposed fluorophore-nitroxide
      hybrids retain all features of the spin labels and fluorescence probes gaining
      new advantages for monitoring redox reactions and radical processes by two
      independent techniques: ESR and steady-state fluorescent spectroscopy. The method
      was applied to the vitamin C analysis in commercial fruit juices.

PMID- 10078872
TI  - Fluorometric method for the enzymatic determination of cholesterol.
AB  - A fluorometric method for the enzymatic determination of cholesterol content has
      been developed using a novel fluorogenic H2O2 probe, Amplex Red. This assay is
      performed in a 96-well microplate, and it is a one-step method amenable to
      automated procedures. Using commercially available cholesterol, our assay allows
      detection of 5 pmol (2 ng) cholesterol per well, which is 100-fold more sensitive
      than published fluorometric and colorimetric methods. When applied to the
      measurement of cholesterol levels in serum and food samples, the Amplex Red-based
      method has been found more attractive since the oxidation product of the Amplex
      Red method has superior long wavelength spectra which are less susceptible to
      interference from the biological compounds.

PMID- 10078873
TI  - Evaluation of a pepscan approach to identify epitopes recognised by anti-hTSH
      monoclonal antibodies.
AB  - In this study, several methodological aspects of the pepscan strategy have been
      investigated with the objective to delineate the amino acid sequences of peptide
      segments that form the epitopes of thyrotropin beta-subunit (TSHbeta) recognised
      by monoclonal antibodies. Hitherto, the pepscan strategy has found application as
      an effective method to identify linear sequence regions that constitute
      contiguous epitopes within the primary structure of some proteins. However, with
      heterodimeric glycoprotein hormones and their subunits such as TSHbeta, as well
      as for many other globular proteins, the majority of the epitopes recognised by
      anti-protein antibodies will be derived from discontinuous segments that
      collectively form the epitope. In these cases the pepscan technique will only be
      able to identify individual segments of the overall discontinuous epitope site as
      linear peptides, some of which may interact with relatively low binding affinity.
      Consequently, additional attention must thus be given to the optimisation of the
      specific binding and detection conditions. Knowledge of the structures of these
      peptide segments can, however, provide a valuable basis to develop peptide
      structures that more closely mimic the topographical features of the epitope in
      the mature, folded protein. In an attempt to identify functional segments
      involved in the epitopes recognised by the anti-hTSH monoclonal antibodies,
      mAb279 and mAb299, the impact of various experimental conditions on the efficacy
      of the pepscan strategy has been investigated. The strategy involved the
      synthesis of a series of overlapping pin-bound octapeptides with amino acid
      sequences derived from the TSH beta-subunit. The ability of these pin-bound
      octapeptides to bind to either mAb279 or mAb299 in ELISA-based assay was then
      determined under conditions involving different concentrations of the primary
      and/or secondary antibodies, and changes in buffer composition, incubation times
      and washing procedures. Theresults of this study illustrate some of the
      constraints and limitations of the pepscan technique when used to delineate
      discontinuous epitopes of globular proteins, as well as providing insight into
      potential avenues to optimise and refine this method.

PMID- 10078874
TI  - Kinetic parameters and tissue distribution of 5-oxo-L-prolinase determined by a
      fluorimetric assay.
AB  - 5-Oxo-L-prolinase (5-OPase) catalyses the hydrolysis of 5-oxo-L-proline to
      glutamate with concomitant stoichiometric cleavage of ATP to ADP, a reaction
      which is known to be part of the gamma-glutamyl cycle-an interrelated series of
      reactions involved in the synthesis and metabolism of glutathione. As recent
      studies indicate, this cyclic pathway plays a crucial role in the regulation of
      amino acid transport. Apparently, the intermediate product 5-oxo-L-proline
      functions as a second messenger molecule that upregulates the activity of certain
      amino acid transport systems. Thus, the degradation of 5-oxo-L-proline by 5-OPase
      leads to the downregulation of this stimulus. In this study, a new sensitive
      fluorimetric assay for 5-OPase activity was established which is based on the
      derivatization of glutamate with o-phthaldialdehyde in the presence of thiols and
      subsequent separation of the products by HPLC. The method is suitable for the
      screening of chromatography fractions as well as for the determination of the
      kinetic parameters Km and Vmax of purified 5-OPase. Additionally, it can be used
      for the measurement of enzyme activity in crude cell extracts and evaluation of
      tissue distribution.

PMID- 10078875
TI  - Mitochondria in neurodegeneration: bioenergetic function in cell life and death.
AB  - The biochemical pathways to cell death in chronic and acute forms of
      neurodegeneration are poorly understood, limiting the ability to develop
      effective therapeutic approaches. As details of the apoptotic and necrotic
      pathways have been revealed, an appreciation for the decisive role that
      mitochondria play in life-death decisions for the cell has grown. As a result,
      the need has arisen to reevaluate the significance to cell viability of
      mitochondrial Ca2+ sequestration, reactive oxygen species generation, and the
      membrane permeability transition. This review provides basic information on these
      mitochondrial functions as they relate to control over cell death.

PMID- 10078876
TI  - Analysis of optical signals evoked by peripheral nerve stimulation in rat
      somatosensory cortex: dynamic changes in hemoglobin concentration and
      oxygenation.
AB  - The origins of reflected light changes associated with neuronal activity (optical
      signals) were investigated in rat somatosensory cortex with optical imaging,
      microspectrophotometry, and laser-Doppler flowmetry, and dynamic changes in local
      hemoglobin concentration and oxygenation were focused on. Functional activation
      was carried out by 2-second, 5-Hz electrical stimulation of the hind limb under
      chloralose anesthesia. These measurements were performed at the contralateral
      parietal cortex through a thinned skull. Regional cortical blood flow (rCBF)
      started to rise 1.5 seconds after the stimulus onset, peaked at 3.5 seconds
      (26.7% +/- 9.7% increase over baseline), and returned to near baseline by 10
      seconds. Optical signal responses at 577, 586, and 805 nm showed a monophasic
      increase in absorbance coincident with the increase in rCBF; however, the signal
      responses at 605 and 760 nm were biphasic (an early increase and late decrease in
      absorbance) and microanatomically heterogeneous. The spectral changes of
      absorbance indicated that the concentrations of both total hemoglobin and
      oxyhemoglobin increased together with rCBF; deoxyhemoglobin, increased slightly
      but distinctly (P = 0.016 at 1.0 seconds, P = 0.00038 at 1.5 seconds) just before
      rCBF increases, then decreased. The authors conclude that activity-related
      optical signals are greatly associated with a moment-to-moment adjustment of rCBF
      and metabolism to neuronal activity.

PMID- 10078877
TI  - Brief vibrotactile stimulation does not increase cortical oxygen consumption when
      measured by single inhalation of positron emitting oxygen.
AB  - Vibrotactile stimulation of the hand elicits no increase in oxygen consumption
      commensurate with the increase in blood flow measured in human sensory cortex. To
      test the hypothesis that previous failures to detect a proportionate increase in
      oxygen consumption could be an artefact of the sequential bolus, or three-step,
      method used to measure this parameter in the human brain in vivo, the authors
      compared the measurements with the results of a novel single bolus, or one-step,
      method of measuring oxygen consumption. The time of completion of the three-step
      method was 40 to 50 minutes, whereas the one-step method lasted only 3 minutes.
      The baseline whole-brain oxygen consumption averaged 185 +/- 32 micromol hg(-1)
      min(-1) by the three-step method and 153 +/- 15 micromol hg(-1) min(-1) by the
      one-step method. Vibrotactile stimulation did not elicit a significant increase
      in oxygen consumption measured by either method. This finding rejects the
      hypothesis that failure to detect an increase of oxygen consumption could be an
      artefact caused by limitations of the method used previously. Conversely, it also
      rejects the hypothesis that observations of an increase of oxygen consumption by
      the new method are artefacts caused by limitations of the one-step method.

PMID- 10078878
TI  - Oxygen consumption of cerebral cortex fails to increase during continued
      vibrotactile stimulation.
AB  - The coupling of oxidative metabolism to the blood flow of the sensory motor hand
      area is uncertain. The authors tested the hypothesis that continued vibrotactile
      stimulation ultimately must lead to increased oxygen consumption consumption.
      Twenty-two healthy right-handed young volunteers underwent positron emission
      tomography (PET) with the [(15)O]water bolus injection method to measure water
      clearance (K1H2O an index of blood flow (CBF), and with the [(15)O]oxygen bolus
      inhalation method to measure CMR(O2). The CMR(O2) was measured 30 seconds and 20
      minutes after onset of intermittent (1 second on, 1 second off) vibrotactile
      stimulation (110 Hz) and compared with baseline measurements without stimulation.
      The K1H2O and CMR(O2) changes (delta K1H2O and delta CMR(O2)) were determined
      using intersubject averaging, together with magnetic resonance imaging based
      stereotaxic registration technique. The K1H2O increase was 21 +/- 4% and 12 +/-
      4% at 30 seconds and 20 minutes after onset of stimulation, respectively. No
      significant increase of CMR(O2) was found until 30 minutes after the onset of
      stimulation. The authors conclude that blood flow and oxidative metabolism
      undergo uncoupling during sustained phasic stimulation of the sensory hand area.
      Therefore, neuronal activity stimulated in this manner does not rely on
      significantly increased oxidative phosphorylation.

PMID- 10078879
TI  - Frequency-dependent changes in cerebral metabolic rate of oxygen during
      activation of human visual cortex.
AB  - To test the hypothesis that brain oxidative metabolism is significantly increased
      upon adequate stimulation, we varied the presentation of a visual stimulus to
      determine the frequency at which the metabolic response would be at maximum. The
      authors measured regional CMR(O2) in 12 healthy normal volunteers with the ECAT
      EXACT HR+ (CTI/Siemens, Knoxville, TN, U.S.A.) three-dimensional whole-body
      positron emission tomograph (PET). In seven successive activating conditions,
      subjects viewed a yellow-blue annular checkerboard reversing its contrast at
      frequencies of 0, 1, 4, 8, 16, 32, and 50 Hz. Stimulation began 4 minutes before
      and continued throughout the 3-minute dynamic scan. In the baseline condition,
      the subjects began fixating a cross hair 30 seconds before the scan and continued
      to do so for the duration of the 3-minute scan. At the start of each scan, the
      subjects inhaled 20 mCi of (15)O-O2 in a single breath. The CMR(O2) value was
      calculated using a two-compartment, weighted integration method. Normalized PET
      images were averaged across subjects and coregistered with the subjects' magnetic
      resonance imaging in stereotaxic space. Mean subtracted image volumes (activation
      minus baseline) of CMR(O2) then were obtained and converted to z statistic
      volumes. The authors found a statistically significant focal change of CMR(O2) in
      the striate cortex (x = 9; y = -89; z = -1) that reached a maximum at 4 Hz and
      dropped off sharply at higher stimulus frequencies.

PMID- 10078880
TI  - Evaluation of dopaminergic presynaptic integrity: 6-[18F]fluoro-L-dopa versus 6
      [18F]fluoro-L-m-tyrosine.
AB  - The effectiveness of 6-[18F]fluoro-L-m-tyrosine (6FMT) to evaluate dopamine
      presynaptic integrity was compared to that of 6-[18F]fluoro-L-dopa (6FDOPA) in
      vivo by positron emission tomography (PET). Six normal and six 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys received 6FDOPA and 6FMT PET
      scans on separate occasions with identical scanning protocols. Four measures, the
      rate of uptake of tracer into striatum using either the arterial input function
      (Ki) or the activity in the occipital cortex as the input function (Kc), the rate
      of loss of striatal radioactivity (k(loss)), and an index of "effective turnover"
      of dopamine (k(loss)/Ki), were obtained for both tracers during extended PET
      studies. 6-[18F]Fluoro-L-m-tyrosine was as effective as 6FDOPA in separating
      normals from MPTP-lesioned subjects on the basis of the uptake rate constants Ki
      and Kc. However, in contrast to 6FDOPA, it was not possible to differentiate the
      normal from the lesioned animal using k(loss) or k(loss)/Ki for 6FMT. Thus, FMT
      appears to be a reasonable, highly specific tracer for studying the activity of
      aromatic dopa decarboxylase enzyme as an index of presynaptic integrity. However,
      if one is interested in investigating further the metabolic pathway and obtaining
      an in vivo estimate of the effective turnover of dopamine (after pharmacologic
      manipulation, for example), 6FDOPA remains the tracer of choice.

PMID- 10078881
TI  - Hyperglycemia and focal brain ischemia.
AB  - The influence of hyperglycemic ischemia on tissue damage and cerebral blood flow
      was studied in rats subjected to short-lasting transient middle cerebral artery
      (MCA) occlusion. Rats were made hyperglycemic by intravenous infusion of glucose
      to a blood glucose level of about 20 mmol/L, and MCA occlusion was performed with
      the intraluminar filament technique for 15, 30, or 60 minutes, followed by 7 days
      of recovery. Normoglycemic animals received saline infusion. Perfusion-fixed
      brains were examined microscopically, and the volumes of selective neuronal
      necrosis and infarctions were calculated. Cerebral blood flow was measured
      autoradiographically at the end of 30 minutes of MCA occlusion and after 1 hour
      of recirculation in normoglycemic and hyperglycemic animals. In two additional
      groups with 30 minutes of MCA occlusion, CO2 was added to the inhaled gases to
      create a similar tissue acidosis as in hyperglycemic animals. In one group CBF
      was measured, and the second group was examined for tissue damage after 7 days.
      Fifteen and 30 minutes of MCA occlusion in combination with hyperglycemia
      produced larger infarcts and smaller amounts of selective neuronal necrosis than
      in rats with normal blood glucose levels, a significant difference in the total
      volume of ischemic damage being found after 30 minutes of MCA occlusion. After 60
      minutes of occlusion, when the volume of infarction was larger, only minor
      differences between normoglycemic and hyperglycemic animals were found.
      Hypercapnic animals showed volumes of both selective neuronal necrosis and
      infarction that were almost identical with those observed in normoglycemic,
      normocapnic animals. When local CBF was measured in the ischemic core after 30
      minutes of occlusion, neither the hyperglycemic nor the hypercapnic animals were
      found to be significantly different from the normoglycemic group. Brief focal
      cerebral ischemia combined with hyperglycemia leads to larger and more severe
      tissue damage. Our results do not support the hypothesis that the aggravated
      injury is caused by any disturbances in CBF.

PMID- 10078882
TI  - An 18-mer peptide fragment of prosaposin ameliorates place navigation disability,
      cortical infarction, and retrograde thalamic degeneration in rats with focal
      cerebral ischemia.
AB  - It was previously reported that prosaposin possesses neurotrophic activity that
      is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat
      saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic
      neuronal damage, the peptide was infused in the left lateral ventricle
      immediately after occlusion of the left middle cerebral artery (MCA) in stroke
      prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the
      ischemia-induced space navigation disability and cortical infarction and
      prevented secondary thalamic degeneration in a dose-dependent manner. In culture
      experiments, treatment with the 18-mer peptide attenuated free radical-induced
      neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at
      higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult.
      Furthermore, a saposin C fragment comprising the 18-mer peptide bound to
      synaptosomal fractions of the cerebral cortex, and this binding decreased at the
      1st day after MCA occlusion and recovered to the preischemic level at the 7th day
      after ischemia. These findings suggest that the 18-mer peptide ameliorates
      neuronal damage in vivo and in vitro through binding to the functional receptor,
      although the cDNA encoding prosaposin receptor has not been determined yet.

PMID- 10078883
TI  - The gene for heparin-binding epidermal growth factor-like growth factor is stress
      inducible: its role in cerebral ischemia.
AB  - The functions of the epidermal growth factor (EGF) family members in the adult
      brain are not known. This study investigated the changes in the expression of
      members of the EGF family following global ischemia employing in situ
      hybridization and immunohistochemical techniques to elucidate their roles in
      pathological conditions. EGF mRNA was not detected in either the control or the
      postischemic rat brain. Although transforming growth factor-alpha (TGF-alpha)
      mRNA was widely expressed in the normal brain, its expression did not change
      appreciably following ischemia. By contrast, heparin-binding EGF-like growth
      factor (HB-EGF) mRNA expression was rapidly increased in the CA3 sector and the
      dentate gyrus of the hippocampus, cortex, thalamus, and cerebellar granule and
      Purkinje cell layers. EGF receptor mRNA, which was widely expressed, also showed
      an increase in the CA3 sector and dentate gyrus. Conversely, HB-EGF mRNA did not
      show any increase prior to ischemic neuronal injury in the CA1 sector, the region
      most vulnerable to ischemia. Immunohistochemical detection of HB-EGF in the
      postischemic brain suggested a slight increase of immunostaining in the dentate
      gyrus of the hippocampus and the cortex. These findings showed that the gene
      encoding HB-EGF is stress-inducible, indicating the likelihood that HB-EGF is a
      neuroprotective factor in cerebral ischemia.

PMID- 10078884
TI  - Lack of histamine synthesis and down-regulation of H1 and H2 receptor mRNA levels
      by dexamethasone in cerebral endothelial cells.
AB  - The purpose of this work was to determine whether cerebral endothelial cells have
      the capacity to synthesize histamine or to express mRNA of receptors that
      specifically respond to available free histamine. The histamine concentrations
      and the expression of L-histidine decarboxylase (HDC) and histamine H1 and H2
      receptor mRNA, both in adult rat brain and in cultured immortalized RBE4 cerebral
      endothelial cells, were investigated. In this study endothelial cells were devoid
      of any kind of detectable histamine production, both in vivo and in the
      immortalized RBE4 cells in culture. Both the immunostainings for histamine and
      the in situ hybridizations for HDC were negative, as well as histamine
      determinations by HPLC, indicating that endothelial cells do not possess the
      capacity to produce histamine. Also, glucocorticoid (dexamethasone) treatment
      failed to induce histamine production in the cultured cells. Although the
      cerebral endothelial cells lack histamine production, a nonsaturable uptake in
      RBE4 cells is demonstrated. The internalized histamine is detected both in the
      cytoplasm and in the nucleus, which could indicate a role for histamine as an
      intracellular messenger. Histamine H1 and H2 receptor mRNA was expressed in RBE4
      cells, and glucocorticoid treatment down-regulated the mRNA levels of both H1 and
      H2 receptors. This mechanism may be involved in glucocorticoid-mediated effects
      on cerebrovascular permeability and brain edema.

PMID- 10078885
TI  - Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of
      hypoxic preconditioning.
AB  - Neuroprotection against cerebral ischemia can be realized if the brain is
      preconditioned by previous exposure to a brief period of sublethal ischemia. The
      present study was undertaken to test the hypothesis that nitric oxide (NO)
      produced from the neuronal isoform of NO synthase (NOS) serves as a necessary
      signal for establishing an ischemia-tolerant state in brain. A newborn rat model
      of hypoxic preconditioning was used, wherein exposure to sublethal hypoxia (8%
      oxygen) for 3 hours renders postnatal day (PND) 6 animals completely resistant to
      a cerebral hypoxic-ischemic insult imposed 24 hours later. Postnatal day 6
      animals were treated 0.5 hour before preconditioning hypoxia with the
      nonselective NOS inhibitor L-nitroarginine (2 mg/kg intraperitoneally). This
      treatment, which resulted in a 67 to 81% inhibition of calcium-dependent
      constitutive NOS activity 0.5 to 3.5 hours after its administration, completely
      blocked preconditioning-induced protection. However, administration of the
      neuronal NOS inhibitor 7-nitroindazole (40 mg/kg intraperitoneally) before
      preconditioning hypoxia, which decreased constitutive brain NOS activity by 58 to
      81%, was without effect on preconditioning-induced cerebroprotection, as was
      pretreatment with the inducible NOS inhibitor aminoguanidine (400 mg/kg
      intraperitoneally). The protective effects of preconditioning were also not
      blocked by treating animals with competitive [3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonate; 5 mg/kg intraperitoneally] or noncompetitive (MK-801; 1 mg/kg
      intraperitoneally) N-methyl-D-aspartate receptor antagonists prior to
      preconditioning hypoxia. These findings indicate that NO production and activity
      are critical to the induction of ischemic tolerance in this model. However, the
      results argue against the involvement of the neuronal NOS isoform, activated
      secondary to a hypoxia-induced stimulation of N-methyl-D-aspartate receptors, and
      against the involvement of the inducible NOS isoform, but rather suggest that NO
      produced by the endothelial NOS isoform is required to mediate this profound
      protective effect.

PMID- 10078886
TI  - Changes in the diffusion of water and intracellular metabolites after excitotoxic
      injury and global ischemia in neonatal rat brain.
AB  - The reduction of the apparent diffusion coefficient (ADC) of brain tissue water
      in acute cerebral ischemia, as measured by diffusion-weighted magnetic resonance
      imaging, is generally associated with the development of cytotoxic edema.
      However, the underlying mechanism is still unknown. Our aim was to elucidate
      diffusion changes in the intracellular environment in cytotoxic edematous tissue.
      The ADC of intracellular metabolites was measured by use of diffusion-weighted 1H
      magnetic resonance spectroscopy after (1) unilateral N-methyl-D-aspartate (NMDA)
      injection and (2) cardiac arrest-induced global ischemia in neonatal rat brain.
      The distinct water ADC drop early after global ischemia was accompanied by a
      significant reduction of the ADC of all measured metabolites (P < 0.01, n = 8).
      In the first hours after excitotoxic injury, the ADC of water and the metabolites
      taurine and N-acetylaspartate dropped significantly (P < 0.05, n = 8). At 24 and
      72 hours after NMDA injection brain metabolite levels were diminished and
      metabolite ADC approached contralateral values. Administration of the NMDA
      antagonist MK-801 1.5 hours after NMDA injection completely normalized the water
      ADC but not the metabolite ADC after 1 to 2 hours (n = 8). No damage was detected
      72 hours later and, water and metabolite ADC had normal values (n = 8). The
      contribution of brain temperature changes (calculated from the chemical shift
      between the water and N-acetylaspartate signals) and tissue deoxygenation to
      ischemia-induced intracellular ADC changes was minor. These data lend support to
      previous suggestions that the ischemia-induced brain water ADC drop may partly be
      caused by reduced diffusional displacement of intracellular water, possibly
      involving early alterations in intracellular tortuosity, cytoplasmic streaming,
      or intracellular molecular interactions.

PMID- 10078887
TI  - A randomized clinical trial of outpatient comprehensive geriatric assessment
      coupled with an intervention to increase adherence to recommendations.
AB  - BACKGROUND: Although comprehensive geriatric assessment (CGA) has been
      demonstrated to confer health benefits in some settings, its value in outpatient
      or office settings is uncertain. OBJECTIVE: To assess the effectiveness of
      outpatient CGA consultation coupled with an adherence intervention on 15-month
      health outcomes. DESIGN: A randomized controlled trial. SETTING: Community-based
      sites. PATIENTS: 363 community-dwelling older persons who had failed a screen for
      at least one of four conditions (falls, urinary incontinence, depressive
      symptoms, or functional impairment) INTERVENTION: A single outpatient CGA
      consultation coupled with an intervention to improve primary care physician and
      patient adherence with CGA recommendations. MEASUREMENTS: Medical Outcomes Study
      Short Form-36 (MOS SF-36), restricted activity and bed days, Physical Performance
      Test, NIA lower-extremity battery. RESULTS: In complete case analysis (excluding
      the five control group subjects who died during the follow-up period), the
      adjusted difference in change scores (4.69 points) for physical functioning
      between treatment and control groups indicated a significant benefit of treatment
      (P = .021). Similar benefits were demonstrated for number of restricted activity
      days and MOS SF-36 energy/fatigue, social functioning, and physical health
      summary scales. In analyses assigning scores of 0 to those who died, these
      benefits were greater, and significant benefits for the Physical Performance Test
      and MOS SF-36 emotional/well being, pain, and mental health summary scales were
      also demonstrated. CONCLUSIONS: A single outpatient comprehensive geriatric
      assessment coupled with an adherence intervention can prevent functional and
      health-related quality-of-life decline among community-dwelling older persons who
      have specific geriatric conditions.

PMID- 10078888
TI  - The effects of aerobic exercise and T'ai Chi on blood pressure in older people:
      results of a randomized trial.
AB  - OBJECTIVE: To compare the effects on blood pressure of a 12-week moderate
      intensity aerobic exercise program and a T'ai Chi program of light activity.
      DESIGN: A randomized clinical trial. SETTING: A suburban clinic in the Baltimore,
      MD, area. PARTICIPANTS: Sixty-two sedentary older adults (45% black, 79% women,
      aged > or = 60 years) with systolic blood pressure 130-159 mm Hg and diastolic
      blood pressure < 95 mm Hg (not on antihypertensive medication). INTERVENTION:
      Participants were randomized to a 12-week aerobic exercise program or a light
      intensity T'ai Chi program. The goal of each condition was to exercise 4 days per
      week, 30 minutes per day. MEASUREMENTS: Blood pressure was measured during three
      screening visits and every 2 weeks during the intervention. Estimated maximal
      oxygen uptake and measures of physical activity level were determined at baseline
      and at the end of the intervention period. RESULTS: Mean (SD) baseline systolic
      and diastolic blood pressures were 139.9 (9.3) mm Hg and 76.0 (7.3) mm Hg,
      respectively. For systolic blood pressure, adjusted mean (SE) changes during the
      12-week intervention period were -8.4 (1.6) mm Hg and -7.0 (1.6) mm Hg in the
      aerobic exercise and T'ai Chi groups, respectively (each within-group P < .001;
      between-group P = .56). For diastolic blood pressure, corresponding changes were 
      3.2 (1.0) mm Hg in the aerobic exercise group and -2.4 (1.0) mm Hg in the T'ai
      Chi group (each within-group P < .001; between-group P = .54). Body weight did
      not change in either group. Estimated maximal aerobic capacity tended to increase
      in aerobic exercise (P = .06) but not in T'ai Chi (P = .24). CONCLUSIONS:
      Programs of moderate intensity aerobic exercise and light exercise may have
      similar effects on blood pressure in previously sedentary older individuals. If
      additional trials confirm these results, promoting light intensity activity could
      have substantial public health benefits as a means to reduce blood pressure in
      older aged persons.

PMID- 10078889
TI  - Blood pressure behavior in the nursing home: implications for diagnosis and
      treatment of hypertension.
AB  - OBJECTIVES: To determine patterns of elevated blood pressure (BP) behavior, their
      clinical correlates, and the relationship to diagnosis and management of
      hypertension. DESIGN: A cross-sectional, prevalence survey. SETTING: Forty-five
      nursing homes owned or managed by a large national chain. PARTICIPANTS: A total
      of 857 older residents (mean age = 84 years). MEASUREMENTS: Supine and standing
      (1 and 3 minutes) BP and heart rate, taken four times in one day (before and
      after breakfast, and before and after lunch) by trained nurses using a random
      zero sphygmomanometer; medication profile; active medical diagnoses; functional
      status; sociodemographics. RESULTS: The prevalence of a single, elevated, supine
      systolic pressure (> or = 160 mm Hg) was 14.3%, and of two to four elevated
      measures was 14.9%. The pre-breakfast reading was consistently the highest, and
      mean systolic pressures decreased after breakfast. Compared with those not
      treated, older residents taking antihypertensive medications had higher systolic
      pressures at all times and showed the same pattern of decline after breakfast.
      Isolated diastolic hypertension was uncommon (0.9%). Cardiovascular disease,
      orthostatic hypotension, diabetes, and use of angiotensin converting enzyme
      inhibitors or calcium channel blockers were more prevalent among older residents
      who had elevated pressures on multiple occasions (P < .03). Successful
      antihypertensive treatment was associated with a lower prevalence of orthostatic
      hypotension. Diuretic use was more likely to be associated with blood pressure
      control. CONCLUSION: The diagnosis of hypertension in frail older people would
      benefit from multiple, within-day measures, including postural BP, taken before
      and after meals. Diuretic use alone, or in conjunction with ACE inhibitors or
      calcium channel blockers, was more likely to be associated with normalized blood
      pressures.

PMID- 10078890
TI  - Management and outcome of acute myocardial infarction in older patients in the
      thrombolytic era.
AB  - OBJECTIVE: Acute myocardial infarction (AMI) is an important cause of mortality
      and morbidity in older patients. The aim of this study was to determine the
      proportion of unselected admissions with AMI that is older than 75 years and to
      examine management and outcomes in this group. DESIGN: An historical cohort study
      of consecutive unselected admissions with AMI identified using the Hospital In
      Patient Enquiry (HIPE) database and validated according to MONICA criteria for
      definite or probable AMI. SETTING: An acute cardiac unit in a university teaching
      hospital/cardiac tertiary referral center. RESULTS: Of 1059 patients, 606 (57%)
      were older than 65 years and 309 (29.2%) were older than 75 years. Mean age in
      this group was 80.5 years. Hospital mortality was almost twice as high as in
      patients younger than 75 years (28% vs 15%, P < .001), and age was an independent
      predictor of short- and long-term mortality following AMI. Women constituted a
      significantly higher proportion of older patients. Family history of AMI and
      cigarette smoking were less prevalent in older patients. Mean cholesterol was
      lower and comorbidities were higher. Other baseline characteristics, including
      previous AMI, did not differ. However older patients were less likely to receive
      thrombolysis (13% vs 36%, P < .001), aspirin (76% vs 86%, P < .01), or beta
      blockers (25% vs 51%, P < .001) and were less likely to undergo cardiac
      catheterization or revascularization. Only 53% were admitted to coronary care.
      CONCLUSION: Patients more than age 75 comprise almost one-third of patients with
      AMI and have a poor prognosis. Although age is an independent predictor of
      mortality following AMI, suboptimal management may contribute to the high
      mortality in these patients.

PMID- 10078891
TI  - Prognostic value of dipyridamole thallium imaging after acute myocardial
      infarction in older patients.
AB  - OBJECTIVE: To assess the utility of intravenous dipyridamole thallium testing for
      predicting major cardiac events following acute myocardial infarction in older
      patients. DESIGN: Prospective cohort study with a median follow-up of 18 months.
      SETTING: A university teaching hospital. PARTICIPANTS: 73 patients aged 65 years
      and older with enzymatically confirmed acute myocardial infarction (mean age 75
      years, 56% male, 71% white). MEASUREMENTS: All patients underwent a detailed
      clinical assessment, an echocardiogram, and an intravenous dipyridamole thallium
      stress test before hospital discharge. The study endpoint was death or nonfatal
      reinfarction during the follow-up period. RESULTS: Overall, 24 patients (33%)
      died or developed recurrent myocardial infarction during follow-up. Among 44
      patients with a reversible thallium defect, 19 (43%) reached the study endpoint,
      compared with only five of 29 patients (17%) without reversible ischemia (P =
      .04). On multivariate analysis, independent prognostic variables included non-use
      of aspirin at hospital discharge (P = .002), decreased left ventricular systolic
      function (P = .009), non-use of a beta-blocker at hospital discharge (P = .013),
      and reversible ischemia on thallium scintigraphy (P = .025). The relative risks
      for death or reinfarction associated with non-use of aspirin, non-use of a beta
      blocker, left ventricular dysfunction, and reversible ischemia were 2.65, 2.39,
      2.01, and 2.51, respectively. Patients with three or four of these risk factors
      had an 83% probability of death or reinfarction, compared with 41% in patients
      with two risk factors and 6% in patients with one or no risk factor (P < .001).
      CONCLUSION: Intravenous dipyridamole thallium imaging provides independent
      prognostic information in older patients with acute myocardial infarction.
      Moreover, the combination of clinical, echocardiographic, and dipyridamole
      thallium variables effectively stratifies older postinfarction patients into high
      , intermediate-, and low-risk categories for death or recurrent myocardial
      infarction.

PMID- 10078892
TI  - Angiotensin-converting enzyme inhibitor use in older patients with heart failure
      and renal dysfunction.
AB  - OBJECTIVE: To examine the relationship between angiotensin-converting enzyme
      (ACE) inhibitor use and clinical outcomes among recently hospitalized patients
      with congestive heart failure (CHF) and coexisting renal insufficiency. DESIGN: A
      prospective cohort study. SETTING: Ten community hospitals in upstate New York.
      PARTICIPANTS: A total of 1076 hospital survivors identified from a consecutive
      series of CHF inpatients. MEASUREMENTS: Patients were followed prospectively for
      6 months after hospital discharge to track mortality, hospital readmission, and
      quality of life. Clinical outcomes were stratified by ACE inhibitor use among
      those with renal dysfunction, defined as serum creatinine > or = 2.0 mg/dL, and
      among the remaining patients, whose serum creatinine was < or = 1.9. RESULTS: ACE
      inhibitor use was lower among 187 patients with renal dysfunction than among 889
      patients with preserved function (41 vs 69%, P < .001). Age and sex were among
      the significant determinants of drug use in both groups. After adjustment for
      covariables, ACE inhibitor use among those with abnormal renal function was not
      associated with a lower risk for death or readmission, or better quality of life.
      By comparison, ACE inhibition conferred meaningful clinical benefit among those
      whose creatinine was < or = 1.9 mg/dL. CONCLUSION: Convincing evidence of
      clinical benefit from ACE inhibitor use is not readily detectable among a sample
      of 187 unselected older patients with CHF and moderate or severe renal
      insufficiency. Further studies to identify subsets of this group who might
      benefit are warranted.

PMID- 10078893
TI  - Effectiveness of behavioral therapy to treat incontinence in homebound older
      adults.
AB  - OBJECTIVES: To examine the (1) short-term effectiveness of behavioral therapies
      in homebound older adults and (2) characteristics of responders and nonresponders
      to the therapies. DESIGN: Prospective, controlled clinical trial with cross-over
      design. SETTING: Adults aged 60 and older with urinary incontinence and who met
      Health Care Financing Administration criteria for being homebound were referred
      to the study by homecare nurses from two large Medicare-approved home health
      agencies in a large metropolitan county in southwestern Pennsylvania. MEASURES:
      Structured continence and medical history, OARS Physical and Instrumental
      Activities of Daily Living scales, Folstein Mini-Mental State Examination Score,
      Clock Drawing Test, Geriatric Depression Scale, Performance-Based Toileting
      Assessment, bladder diaries, and physical examination. RESULTS: One hundred five
      subjects were randomized to biofeedback-assisted pelvic floor muscle training (53
      to the treatment group and 52 to the control groups). Control subjects with
      complete pre- and post-control data (n = 45) experienced a median 6.4% reduction
      in urinary accidents in contrast to a median 75.0% reduction in subjects with
      complete pre- and post-treatment data (n = 48, P < .001). Following the control
      phase, subjects crossed over to the treatment protocol. Eighty-five subjects
      completed treatment, achieving a median 73.9% reduction in UI. Exercise adherence
      was the most consistent predictor of responsiveness to the behavioral therapy.
      CONCLUSIONS: Clinically significant reductions in urinary incontinence are
      achievable with behavioral therapies in many cognitively intact homebound older
      adults despite high levels of co-morbidity and functional impairment.

PMID- 10078894
TI  - The effect of major depression on functional status in patients with coronary
      artery disease.
AB  - OBJECTIVE: To examine the effect of major depression on reported functional
      status in a group of patients with coronary artery disease (CAD). SETTING: An
      inpatient cardiology service. PARTICIPANTS: Three hundred thirty-five inpatients
      with coronary artery disease who were free of dementia, Parkinson's disease, and
      other primary neurological illnesses. MEASUREMENTS: Duke Depression Evaluation
      Schedule, a structured psychiatric interview which included the Diagnostic
      Interview Schedule depression subscale, the Cumulative Illness Rating Scale, and
      two scales for measuring instrumental and self-maintenance activities of daily
      living. RESULTS: Twenty-seven subjects met DSM-IV criteria for major depression.
      Compared with subjects without major depression, depressed subjects were more
      than twice as likely to report a self-maintenance ADL deficit and were
      significantly more likely to report an IADL deficit than were nondepressed
      subjects (93 vs 71%). In regression models, female gender, older age, greater
      medical illness severity, and presence of major depression were significant
      predictors of self-maintenance ADL disability; and female gender, older age,
      greater medical severity, and presence of major depression significantly
      predicted greater IADL impairment. CONCLUSION: The presence of major depression
      was associated with functional disability in patients with CAD. Further research
      is needed to clarify whether antidepressant treatment significantly impacts both
      affective symptoms and functional status in patients with coronary heart disease.

PMID- 10078895
TI  - Influence of companion animals on the physical and psychological health of older
      people: an analysis of a one-year longitudinal study.
AB  - OBJECTIVE: To examine whether companion animals or attachment to a companion
      animal was associated with changes in physical and psychological health in older
      people and whether the relationships between physical and psychological health
      and human social networks were modified by the presence or absence of a companion
      animal. DESIGN: A 1-year longitudinal study with standardized telephone interview
      data collected at baseline and repeated at 1-year SETTING: Wellington County,
      Ontario, Canada PARTICIPANTS: An age- and sex stratified random sample (baseline
      n = 1054; follow-up n = 995) of noninstitutionalized adults aged 65 and older
      (mean age = 73, SD +/- 6.3) MEASUREMENTS: Social Network Activity was measured
      using a family and non-family social support scale, participation in an organized
      social group, involvement in the affairs of the social group, the practice of
      confiding in others, feelings of loneliness, and the perceived presence of
      support in a crisis situation. Chronic conditions were measured as the current
      number of selected health problems. Pet ownership was assessed by the report of
      owning a dog or a cat and the Lexington Attachment to Pets Scale score. Physical
      health was assessed as the ability to perform Activities of Daily Living (ADLs).
      Psychological health was measured as a summed score comprising the level of
      satisfaction regarding one's health, family and friend relationships, job,
      finances, life in general, overall happiness, and perceived mental health.
      Sociodemographic variables assessed include subject age, sex, marital status,
      living arrangements, education, household income, and major life events. RESULTS:
      Pet owners were younger, currently married or living with someone, and more
      physically active than non-pet owners. The ADL level of respondents who did not
      currently own pets deteriorated more on average (beta = -.270, P = .040) than
      that of respondents who currently owned pets after adjusting for other variables
      during the 1-year period. No statistically significant direct association was
      observed between pet ownership and change in psychological well-being (P > .100).
      However, pet ownership significantly modified the relationship between social
      support and the change in psychological well-being (P = .001) over a 1-year
      period. CONCLUSIONS: The results demonstrate the benefits of pet ownership in
      maintaining or slightly enhancing ADL levels of older people. However, a more
      complex relationship was observed between pet ownership and an older person's
      well-being.

PMID- 10078896
TI  - Age-related brain changes associated with motor function in healthy older people.
AB  - OBJECTIVE: To identify the MRI imaging findings associated with motor changes in
      healthy older people. DESIGN: A cross-sectional study. SETTING: A study of
      neurologic function in very healthy older people, the Oregon Brain Aging Study.
      PARTICIPANTS: Clinical and MRI data were examined in 50 very healthy older
      subjects (mean age = 85.1, SD = 7.2 years). MEASUREMENTS: Clinical measures
      (finger tapping, hand opening and closing, steps and time to walk 30 feet and
      timed standing on one foot) were dependent variables in multiple regression
      analyses using age and the following MRI measures as independent variables: total
      brain volume (TBV)/intracranial volume; ventricular volume/TBV; periventricular
      high signal/TBV; deep high signal/TBV. RESULTS: The number of steps and the time
      to walk 30 feet were each associated with periventricular high signal (steps: r =
      .58, P < .001; time: r = .60, P < .001) and ventricular volume (steps: r = .54, P
      < .001; time: r = .58, P < .001). These associations remained significant after
      adjusting for age. None of the other clinical variables was associated with the
      MRI volumes. CONCLUSIONS: Gait measures were associated significantly with
      periventricular high signal and ventricular volume. These CNS changes contribute
      to the cause of these important markers of aging.

PMID- 10078897
TI  - The driving habits of adults aged 60 years and older.
AB  - OBJECTIVES: We describe the driving habits of adults aged 60 years and older who
      were interviewed in the context of a community survey focused on mental
      disturbances. Our goal was to identify clinical cues that might signal driving
      difficulty in older adults who might present to the primary care physician for
      health care. DESIGN: A population-based survey. SETTING: Continuing participants
      in a follow-up study of community-dwelling adults who were living in East
      Baltimore in 1981. PARTICIPANTS: Subjects were 1920 continuing participants of
      the Baltimore sample of the Epidemiologic Catchment Area Program; 589 were aged
      60 years and older and provided information on driving habits. MEASUREMENTS:
      Respondents were asked about their driving status: had they made adaptations to
      driving and had they experienced any adverse driving events in the 2 years before
      the interview. Driving behaviors were assessed in relation to chronic disease,
      sensory impairment, functional status, and mental status. RESULTS: Former drivers
      were more likely to be older, female, and nonwhite. Diabetes, vision impairment,
      functional impairment, and making an error on the copy design task of the Mini
      Mental State Examination (MMSE) were associated with no longer driving. Women
      were more likely to report having made adaptations to driving, as were persons
      with heart disease, arthritis, vision impairment, and those who made an error on
      the copy design task of the MMSE. Heart disease and hearing impairment were
      associated with report of an adverse driving event. In multivariate models that
      included terms for potentially influential characteristics such as age, gender,
      and miles driven, only the copy design task was associated with driving status,
      and only heart disease was associated with driving adaptation and adverse driving
      events. CONCLUSION: Simple tests that tap visuospatial ability, such as the copy
      design task of the MMSE, may warrant additional study for use in driving
      assessment of older adults in primary care. The results underscore the importance
      of making an inquiry about driving as a separate and independent component of
      functional assessment.

PMID- 10078898
TI  - Predictors of continued physical restraint use in nursing home residents
      following restraint reduction efforts.
AB  - OBJECTIVES: To examine predictors of continued restraint use in nursing home
      residents following efforts aimed at restraint reduction. DESIGN: Secondary
      analysis of data from a clinical trial using a one-group, pre-test post-test
      design. SETTING: Three nonprofit, religion-affiliated nursing homes in a
      metropolitan area. PARTICIPANTS: The sample consisted of 201 physically
      restrained nursing home residents. Following restraint reduction efforts, 135 of
      the sample were still restrained. Mean age of participants was 83.9 years.
      MEASUREMENTS: Physical restraint use was measured by observation and included any
      chest/vest, wrist, mitt, belt, crotch, suit, or harness restraint plus any sheet
      used as restraint or a geriatric chair with fixed tray table. Nursing home
      residents were subjected to any one of three conditions aimed at restraint
      reduction, including adherence to the mandate of the Omnibus Budget
      Reconciliation Act of 1987 (OBRA '87), staff education, and education with
      consultation from a gerontological clinical nurse specialist. Resident
      characteristics including dependency, health status, mental status, depression,
      behavior, fall risk; presence of treatment devices and institutional factors were
      determined. RESULTS: Physical dependency, lower cognitive status, behavior,
      presence of treatment devices, presence of psychiatric disorders, fall risk, and
      fall risk as staff rationale for restraint were associated (P < .10) with
      continued restraint use. Nursing hours, staff mix, prevalence of restraint use by
      unit, and site were also associated (P < .10) with continued use of physical
      restraints. Following bivariate analysis, associated resident characteristics
      were subjected to logistic regression. Lower cognitive status (OR = 2.4 (for
      every 7-point decrease in MMSE), 95% CI, 1.7, 3.3) and fall risk as staff
      rationale for restraint (OR = 3.5, 95% CI., 1.5, 8.0) were predictive of
      continued restraint use. Adding nursing hours, staff mix, and prevalence of
      restraint use by unit to the logistic regression model was not statistically
      significant (partial chi-square = 2.79, df = 6, P = .834). Nursing home site was
      added to the model without changing the significance (P < .05) of cognitive
      status or fall risk as a staff rationale for restraint use. CONCLUSION: Continued
      restraint use in nursing home residents in this study most often occurred with
      severe cognitive impairment and/or when fall risk was considered by staff as a
      rationale for restraint. Efforts to reduce or eliminate physical restraint use
      with these groups will require greater efforts to educate staff in the assessment
      and analysis of fall risk, along with targeted interventions, particularly when
      cognition is also impaired.

PMID- 10078899
TI  - Survival after percutaneous endoscopic gastrostomy among older residents of
      Quebec.
AB  - CONTEXT: Percutaneous endoscopic gastrostomy has become a mainstay of nutritional
      support for individuals with swallowing dysfunction. There is little population
      based data to guide the use of this intervention in older individuals. OBJECTIVE:
      To describe the use of percutaneous endoscopic gastrostomy among older residents
      of Quebec and to evaluate patient characteristics associated with subsequent
      survival and hospital discharge. DESIGN: A population-based cohort study.
      SETTING: Quebec, Canada. PATIENTS: 175 individuals with a billing claim for
      percutaneous endoscopic gastrostomy performed in 1993. MEASUREMENTS: Billing and
      hospitalization databases were used to collect patient characteristics, medical
      diagnoses, discharge destinations, and dates of death. The relationships between
      demographic and diagnostic variables before gastrostomy, and subsequent survival
      and discharge home, were evaluated using survival analysis. RESULTS: Median
      survival after gastrostomy was 210 days. Mortality at 30 days was 18.3%.
      Decreased survival was associated with a previous diagnosis of malignancy (risk
      ratio (RR) = 1.71; 95% CI, 1.09-2.68); mortality did not increase with increasing
      age. Of 163 individuals hospitalized at the time of gastrostomy, 42 (26%) were
      discharged home. Individuals with a previous diagnosis of stroke (RR = 2.80; 95%
      CI 1.01-7.77) were more likely to be discharged home than other individuals.
      CONCLUSIONS: Survival after percutaneous endoscopic gastrostomy is poor; the
      requirement for such a procedure appears to be a marker for severe underlying
      disease. The greater likelihood of return home after gastrostomy among
      individuals with stroke suggests that the use of this intervention as an adjunct
      to rehabilitation is appropriate in these individuals.

PMID- 10078900
TI  - Secondary hyperparathyroidism in patients from Western Australia with hip
      fracture: relationship to type of hip fracture, renal function, and vitamin D
      deficiency.
AB  - OBJECTIVES: To determine the frequency of vitamin D deficiency and secondary
      hyperparathyroidism in Australian hip fracture patients living in the community.
      PATIENTS: A total of 283 consecutive patients with hip fracture admitted over a
      15-month period to a university teaching hospital in Western Australia. Included
      were residents of hostels for the elderly, and excluded were nursing home
      residents and those with malignant fractures. METHOD: Data collected included
      biochemistry (25 hydroxyvitamin D, parathyroid hormone and creatinine levels),
      measurements of function and disability (Barthel Index, Frenchay Activity Index),
      sunshine exposure, and basic demographics. RESULTS: Vitamin D deficiency occurred
      in 31.7% and secondary hyperparathyroidism occurred in 17.7% of cases. The major
      determinants of vitamin D deficiency were outdoor sunshine exposure, ambient
      daily sunshine, and disability (low Frenchay Activity Index or ADL difficulty).
      Secondary hyperparathyroidism was related to older age, renal dysfunction, and
      vitamin D deficiency. Secondary hyperparathyroidism was associated with an excess
      of trochanteric over subcapital hip fractures. CONCLUSIONS: Secondary
      hyperparathyroidism appears to be a heterogeneous condition, caused in
      approximately equal proportions by vitamin D deficiency and renal dysfunction,
      that may confer increased cortical bone fragility and trochanteric fractures.
      Renal dysfunction in old age may be an important additional determinant of senile
      osteoporosis, which has implications for preventive therapy. Vitamin D deficiency
      occurs in disabled and, presumably, housebound older people despite near optimal
      climatic conditions.

PMID- 10078901
TI  - Risk factors for lack of recovery of ADL independence after hospital discharge.
AB  - OBJECTIVE: To determine risk factors for lack of recovery of independent
      functioning after hospitalization for acute medical illness. DESIGN: Secondary
      analysis of cohort study of patients receiving home nursing after discharge.
      SETTING: Evaluations performed in the home after discharge and 1 month later.
      PARTICIPANTS: A total of 73 adults aged 65 years and older who were independent
      in activities of daily living (ADLs) before hospitalization and dependent at
      discharge. MEASUREMENTS: Self-report and objective measures of function,
      mobility, and cognition. OUTCOME: Return to independence in ADLs 1 month after
      discharge. RESULTS: Fifty-nine percent of patients did not return to previous ADL
      independence by 1 month postdischarge. The likelihood for not recovering was 87%
      (95% CI, 70-100%) if a patient had a Mini-Mental State Examination score (MMSE) <
      24 at discharge (P = .015). Among patients with good cognition, 85% (95% CI, 66
      100%) of those who used an assistive device indoors before hospitalization did
      not recover (P = .007). Among patients with good cognition and no previous
      assistive device use, 73% (95% CI, 47-99%) of those with a Timed "Up and Go" of >
      or = 40 seconds did not recover (P = .012). The likelihood of recovery was high
      (76%, 95% CI 56-96%) if a patient had no assistive device prehospital, a good
      MMSE, and a Timed "Up and Go" of < 20 seconds. CONCLUSION: We hypothesize that a
      classification strategy using cognition, prehospital mobility, and discharge
      physical performance will predict patients who are less likely to recover
      functional independence after hospitalization. If this is validated in future
      study, it may help clinicians identify patients who are more likely to benefit
      from additional intervention.

PMID- 10078902
TI  - Incidence of new thromboembolic stroke in persons 62 years and older with chronic
      atrial fibrillation treated with warfarin versus aspirin.
AB  - OBJECTIVE: To investigate the incidence of new thromboembolic (TE) stroke in
      older persons with chronic atrial fibrillation treated with oral warfarin versus
      aspirin. DESIGN: In an observational study of 312 older persons with chronic
      atrial fibrillation, long-term aspirin 325 mg daily was administered to 187
      persons, and oral warfarin, in a dose adjusted to maintain the international
      normalized ratio (INR) between 2.0 and 3.0, was administered to 115 persons. The
      incidence of new TE stroke was analyzed in persons treated with warfarin versus
      aspirin at 36 +/- 17 months (1 to 99 months) follow-up. SETTING: A large, long
      term healthcare facility. PATIENTS: The patients included 208 women and 104 men,
      mean age 84 +/- 7 years (range 62 to 101 years). MEASUREMENTS AND MAIN RESULTS:
      Four of 125 persons (3%) on warfarin stopped taking warfarin compared with four
      of 187 persons (2%) on aspirin who stopped taking aspirin because of adverse
      effects (P not significant). In persons with prior stroke, the incidence of new
      TE stroke was 40% (27 of 67) in persons treated with warfarin versus 81% (56 of
      69) in persons treated with aspirin (P < .001). In persons with no prior stroke,
      the incidence of new TE stroke was 22% (13 of 58) in persons treated with
      warfarin versus 56% (66 of 118) in persons treated with aspirin (P < .001). The
      incidence of new TE stroke in all subjects was 32% (40 of 125) in persons treated
      with warfarin versus 65% (122 of 187) in persons treated with aspirin (P < .001).
      Cox regression analysis showed that persons taking warfarin had a 76% less chance
      of developing a new TE stroke than those taking aspirin after controlling the
      confounding effects of other risk factors. CONCLUSION: In an observational study
      of older persons with chronic atrial fibrillation, persons treated with oral
      warfarin to maintain an INR between 2.0 and 3.0 had a significantly lower
      incidence of new TE stroke than persons treated with oral aspirin 325 mg daily.

PMID- 10078903
TI  - Human cloning recommended for therapeutic research holds promise for treating
      Parkinson's and Alzheimer's diseases.

PMID- 10078904
TI  - Outpatient comprehensive geriatric assessment: an intervention whose time has
      come, or has it?

PMID- 10078905
TI  - Measuring blood pressure and treating hypertension in (frail) older people.

PMID- 10078906
TI  - Restraint reduction and legal risk management.

PMID- 10078907
TI  - Risperdal advertising in JAGS. Journal of the American Geriatrics Society.

PMID- 10078908
TI  - In re: Fellows LK, competency and consent in dementia.

PMID- 10078909
TI  - Palliative care and severe dementia.

PMID- 10078910
TI  - Donepezil for postoperative delirium associated with Alzheimer's disease.

PMID- 10078911
TI  - Recurrent, refractory hypoglycemia presenting as a behavioral disorder in an
      older woman.

PMID- 10078912
TI  - Driving simulation performance predicts future accidents among older drivers.

PMID- 10078913
TI  - Congenital disseminated malignant rhabdoid tumor: a distinct clinicopathologic
      entity demonstrating abnormalities of chromosome 22q11.
AB  - The clinical, pathologic, and immunohistochemical features of a widely
      disseminated tumor with rhabdoid phenotype are described in nine infants < or = 3
      months of age. Five neonates had tumor evident at birth, two of which had
      placental metastases. The average survival following diagnosis was < 6 weeks.
      None of the infants had an apparent primary tumor in either the kidney or brain.
      In four cases, the dominant mass involved the head and neck region, and in two
      cases, the primary mass was paraspinal. The histologic features were those of a
      high-grade, round cell neoplasm with abundant cytoplasm and containing cells with
      cytoplasmic filamentous inclusions. Immunohistochemical studies revealed
      polyphenotypic antigen expression. Genetic information was available from eight
      of nine cases. Karyotype analysis revealed abnormalities of chromosome band 22q11
      12 in three of six tumors. Fluorescence in situ hybridization studies or
      molecular studies demonstrated 22q11.2 deletions in all five cases with available
      frozen tissue, two of which had translocations involving 22q by karyotype
      analysis. The similar clinical and pathologic findings in these rapidly fatal
      tumors in infants and the demonstration of abnormalities of chromosome 22q11 in a
      majority of the cases supports their histogenetic and nosologic relationship to
      the family of malignant rhabdoid tumors that typically occur in young children in
      several anatomic sites, including kidney, soft tissues, liver, and brain. Like
      neuroblastoma and rhabdomyosarcoma, malignant rhabdoid tumor can appear as
      disseminated disease at birth or shortly thereafter.

PMID- 10078914
TI  - How often are diagnostic features missed with less extensive histologic sampling
      of prostate needle biopsy specimens?
AB  - The authors determined whether clinically relevant diagnostic information would
      be lost by examination of <3 levels per tissue core in prostate needle biopsy
      specimens. They evaluated 439 consecutive sextant biopsy specimens for the
      following three histopathologic features: presence of adenocarcinoma involving
      one core, Gleason pattern 4 in cases of grade 3 + 4 = 7 adenocarcinoma, and
      perineural invasion (PNI) by carcinoma. For all cases, 3 levels from each
      involved core were reviewed for the presence or absence of these three features.
      In 50 cases with adenocarcinoma involving only 1 core, diagnostic carcinoma was
      present on all 3 levels in 43 cores (86%). Carcinoma was present on only 2 levels
      in 3 cores (6%), present only on 1 level in 3 cores (6%), and present only on
      additional cut-downs, not on the original 3 levels in 1 core (2%). Among 32
      cases, 51 cores were identified that contained Gleason grade 3 + 4 = 7
      adenocarcinoma. In 41 cores (80%), pattern 4 was identified in all 3 levels. In 5
      cores (10%), pattern 4 was identified on only 2 levels, and in another 5 cores
      (10%), pattern 4 was present on only 1 level. Among 36 cases, 69 tissue cores
      were identified that contained perineural invasion (PNI). In 54 cores (78%), PNI
      was present on all 3 levels. In 7 cores (10%), PNI was present on only 2 of 3
      levels, while in 7 other cores (10%), PNI was present on only 1 of 3 levels. In 1
      core (1.5%), PNI was noted only on additional cutdowns, not on the original 3
      levels. We estimated that reducing the number of levels to 1 per core could
      result in the misdiagnosis of PNI, grading, or carcinoma in approximately 8-11%
      of cores with these features and could have changed the case diagnosis in 9 of
      439 cases. If only 2 levels were reviewed, we predict misdiagnosis in 5% to 6% of
      cores with these features and a change in the case diagnosis in 5 of 439 cases.
      Misdiagnosis of clinically relevant features on prostate biopsy specimens can be
      minimized with histologic review of 3 levels per tissue core.

PMID- 10078915
TI  - Optimal histopathologic examination of the sentinel lymph node for breast
      carcinoma staging.
AB  - Sentinel lymph node dissection is a minimally invasive surgical technique for
      staging of breast carcinoma. The optimal pathologic examination of the sentinel
      node (SN) has not yet been determined. Our standard protocol for evaluation of
      the SN in patients with breast cancer included frozen section at one level, plus
      paraffin sections at two levels, separated by 40 microm, and stained with
      hematoxylin and eosin and cytokeratin immunohistochemistry (IHC) at each paraffin
      section level. In the current study, we evaluated the use of step sections and
      cytokeratin IHC in 60 SNs (42 consecutive patients) that were tumor-negative on
      frozen section and hematoxylin and eosin staining at permanent section levels 1
      and 2. The SN were reexamined with cytokeratin IHC at eight additional levels
      (levels 3-10) of the paraffin block, each separated by 40 microm. Previous IHC
      sections from levels 1 and 2 had shown micrometastases in nine SNs (eight
      patients) and no tumor cells in the remaining 51 SNs (34 patients). Of the 51
      previously negative SNs, only two (4%) SNs from one (3%) patient had metastatic
      carcinoma cells in levels 3-10. Thus, the additional step sections with
      cytokeratin IHC did not significantly increase the number of patients with tumor
      positive SNs. We currently recommend that the SN be examined with cytokeratin IHC
      at two levels of the paraffin block. This should optimize sentinel lymph node
      dissection as a staging technique and minimize the labor and financial burden
      associated with multiple step sections and IHC stains.

PMID- 10078916
TI  - Synovial sarcoma of the extremities: a clinicopathologic study of 34 cases,
      including semi-quantitative analysis of spindled, epithelial, and poorly
      differentiated areas.
AB  - Many clinicopathologic studies of synovial sarcoma have grouped together tumors
      from different sites. The goal of this study was to identify clinical and
      pathologic features that correlate with a poor outcome in patients with extremity
      synovial sarcoma. Thirty-four cases of synovial sarcoma of the extremities were
      studied. Inclusion criteria included a consistent histology, the
      immunohistochemical expression of at least one epithelial marker (AE1/3, CAM 5.2,
      or epithelial membrane antigen), and adequate clinical follow-up. Features
      evaluated included the presence and extent of spindled, epithelial, and poorly
      differentiated areas, the presence and extent of calcification and necrosis,
      nuclear grade, the presence or absence of cells with a rhabdoid morphology, and
      the number of mitotic figures (MFs) per 10 high power fields (HPFs). Patients
      were considered to have an adverse outcome if they developed metastatic disease
      or died from tumor. The cohort included 15 males and 19 females with a median age
      36 years (range, 11-82 years). There were 22 lower extremity tumors and 12
      located on the upper extremities. Tumor size ranged from 1.2 to 16 cm (median, 6
      cm). Follow-up ranged from 9 to 108 months (median, 38 months). Eleven (32%)
      patients had an adverse outcome, all with metastatic disease. Features associated
      with an adverse outcome included increasing age (p = 0.04), tumor size of 5 cm or
      greater (p = 0.03), tumor location on the lower extremities (p = 0.04), the
      presence of poorly differentiated areas (p = 0.04), grade 3 nuclei (p = 0.005),
      cells with a rhabdoid morphology (p = 0.003), and more than 10 MFs/10 HPFs (p =
      0.005). Patients whose tumors were composed of at least 20% poorly differentiated
      areas were significantly more likely to have an adverse outcome (p < 0.001). In
      conclusion, a variety of clinical and pathologic features are associated with an
      adverse outcome in patients with synovial sarcoma of the extremities. These
      features include increasing age, tumor size of 5 cm or more, lower extremity
      tumor location, the presence of poorly differentiated areas, particularly when at
      least 20% of the tumor, grade 3 nuclei, rhabdoid cells, and more than 10 MFs/10
      HPFs.

PMID- 10078917
TI  - Metastatic melanoma to the skin simulating blue nevus.
AB  - Cutaneous metastases from melanoma can mimic primary melanoma and melanocytic
      nevi. Recognition of a metastatic lesion is of great importance for proper
      staging and treatment decisions. In this study, a potential diagnostic pitfall is
      described and discussed: dermal metastases from cutaneous melanoma simulating
      blue nevus, a phenomenon that has received little attention. Ten blue nevus-like
      lesions from three patients are presented. All contained pigmented melanocytes
      and melanophages in variable proportions arranged in a blue nevus-like growth
      pattern. The blue nevus-like metastases occurred in the same anatomic region as
      the primary tumor or, as in one patient, near the skin scar of a dissected lymph
      node metastasis. Histologic clues of metastatic melanoma included the presence of
      atypical epithelioid melanocytes, mitotic figures, and an associated inflammatory
      cell infiltrate at the periphery of the lesion. Although such histologic features
      facilitate the recognition of a metastasis, clinical correlation is essential for
      a definitive diagnosis.

PMID- 10078918
TI  - Melanocytic nevi of palms and soles: a histological study according to the plane
      of section.
AB  - Melanocytic nevi of palms and soles (MNPS) cause diagnostic problems to
      dermatopathologists because they share histologic features with malignant
      melanoma (MM). Early MNPS frequently display a striate appearance, suggesting
      that, in this subset of nevi, both melanocytes and melanin might have a
      particular distribution in relation to dermatoglyphics. To verify this
      hypothesis, we undertook a histological study on 78 junctional MNPS sampled along
      a plane either perpendicular or parallel to dermatoglyphics. Histologic
      examination revealed symmetry in 56% of the lesions, circumscription in 60%,
      intraepidermal scatter of melanocytes in 79%, and melanin columns in 61%.
      Interestingly, comparison between histologic features of nevi sampled
      perpendicularly and those of nevi cut parallely to dematoglyphics showed that
      features of benignity, namely symmetry, circumscription and melanin columns, were
      significantly more frequent in lesions dissected along a perpendicular plane.
      Moreover, in 70% of perpendicular samples, intraepidermal scatter of melanocytes
      and melanin columns were strictly concentrated in furrows. Therefore, to avoid
      diagnostic pitfalls in the differentiation between junctional MNPS and MM, we
      strongly suggest to dissect MNPS along a plane perpendicular to skin markings. We
      hypothesize that mechanical stress can be responsible for concentration of
      intraepidermal scatter of melanocytes and melanin columns in skin furrows.

PMID- 10078919
TI  - Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of
      p27Kip1 protein.
AB  - The histologic spectrum of proliferative parathyroid lesions (hyperplasia,
      adenoma, and carcinoma) often overlap, and differentiation between these lesions
      may at times be difficult. p27kip1 (p27) is a cyclin-dependent kinase inhibitor
      that helps regulate the transition from the G1 to the S phase of the cell cycle.
      Significantly higher levels of p27 expression have been detected in some normal
      tissues than in their neoplastic counterparts. The authors analyzed a series of
      parathyroid lesions to determine if expression of this cell cycle protein may be
      useful in distinguishing between parathyroid hyperplasia, adenomas, and
      carcinomas. Formalin-fixed paraffin-embedded tissues from randomly selected
      patients (22 histologically normal parathyroid glands, 33 cases of hyperplasia,
      43 adenomas, and 17 carcinomas) were analyzed for expression of p27 by
      immunostaining. All cases were also immunostained for Ki67 with antibody MIB-1.
      The distribution of immunoreactivity was analyzed by quantifying the percentage
      of positive nuclei that was expressed as the labeling index (LI). In situ
      hybridization (ISH) for p27 mRNA was done using a cRNA probe with 30 of these
      cases. Normal parathyroid glands had the highest p27 LI (89.6 +/- 1.4), followed
      by hyperplasia (69.6 +/- 7.5), adenomas (56.8 +/- 3.4), and carcinomas (13.9 +/-
      2.6). ISH showed no differences in p27 mRNA, indicating that the expression of
      the p27 gene was controlled at a posttranslational level in parathyroid tissues.
      Ki67 expression was significantly higher in carcinomas (LI = 8.4 +/- 1.9) than in
      adenomas (LI = 2.7 +/- 0.2) and hyperplasia (LI = 3.3 +/- 0.4). These results
      suggest that both p27 and Ki67 may be helpful in the diagnosis of histologically
      difficult parathyroid lesions.

PMID- 10078920
TI  - Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.
AB  - DNA ploidy analysis of prostate needle biopsy specimens was performed to
      determine whether ploidy status could predict tumor grade shifting at radical
      prostatectomy. The paired needle biopsy and radical prostatectomy specimens from
      111 randomly selected men with prostate cancer were obtained from the surgical
      pathology files of the Albany Medical Center Hospital. The original tumor grades
      were assigned by a staff of 12 surgical pathologists according to the Gleason
      system. Tumors with original Gleason scores < or = 6 were classified as low
      grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy
      analysis was performed on the needle biopsy specimens using the CAS 200 image
      analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on
      Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid
      cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy
      to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%)
      were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10
      (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade
      needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%)
      featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of
      aneuploid low-grade tumors on needle biopsy became high-grade at radical
      prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became
      low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade
      were incongruous, 28 (74%) had grade shifting. In a multivariate regression
      analysis, a high-grade Gleason score on radical prostatectomy specimens
      correlated significantly with needle biopsy ploidy (p = 0.0001) but not with
      needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the
      detection of high-grade tumors on radical prostatectomy was 30%, and the
      specificity was 86%. The sensitivity of ploidy status in the prediction of high
      grade at radical prostatectomy was 78%, and the specificity was 96%. With a
      prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post
      radical prostatectomy disease recurrence on a subset of 106 patients, on
      univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p
      = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy
      grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status
      independently predicted disease recurrence (p = 0.002), whereas needle biopsy and
      prostatectomy grade did not. These results indicate that DNA ploidy analysis of
      needle biopsy specimens of prostate cancer predicts grade shifting, that it is a
      more sensitive and specific indicator of final tumor grade at radical
      prostatectomy than is the original needle biopsy grade, and that ploidy status
      independently predicts postoperative disease recurrence.

PMID- 10078921
TI  - Nodular lymphoid lesion of the liver: an immune-mediated disorder mimicking low
      grade malignant lymphoma.
AB  - Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in
      the liver were studied in the authors' surgical pathology laboratory. These
      lesions posed difficulty in diagnosis, and their differentiation from low-grade
      lymphoma was not possible on histopathologic evaluation alone. The liver masses
      were analyzed histologically and immunohistochemically as well as for clonal
      immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene
      rearrangements. The lesions were seen as solitary grossly distinct firm nodules
      in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their
      greatest dimensions. Two were found in livers removed because of end-stage
      primary biliary cirrhosis at the time of orthotopic liver transplantation, and
      the third was an incidental finding during laparotomy. Microscopically, these
      were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with
      varying degrees of admixed acute inflammatory cells and scattered lymphoid
      follicles. By immunohistochemistry and molecular studies, these were found to be
      reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13
      years, respectively. It is concluded that these cases represent a unique type of
      nodular lymphoid lesion, which is probably an immune-mediated benign reactive
      hyperplasia. It constitutes an entity by itself and must be distinguished from
      low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and
      molecular studies are required.

PMID- 10078922
TI  - Documentation of EWS gene rearrangements by fluorescence in-situ hybridization
      (FISH) in frozen sections of Ewing's sarcoma-peripheral primitive neuroectodermal
      tumor.
AB  - Prompt and accurate diagnosis of small round cell tumors warrants ancillary
      studies. Recently, two-color fluorescence in-situ hybridization (FISH) using
      probes for specific gene rearrangements has gained wide acceptance. EWS gene
      rearrangements, present in essentially 100% of Ewing's Sarcoma/peripheral
      primitive neuroectodermal tumor, were evaluated by FISH on frozen sections (FS)
      of tumor biopsies from 10 patients, plus a negative control, and in seven other
      malignant neoplasms of childhood. 4mu FS were hybridized overnight, using a
      single EWS gene-specific probe spanning the EWS breakpoint. We identified EWS
      rearrangements in 8 of 10 cases (80%) of Ewing's Sarcoma/pPNET. There are no
      known false positives in diploid or near-diploid tumors, or in any of the non-EWS
      tumors tested; the uncommon false negative can be confirmed by RT-PCR.
      Hyperdiploid cases with multiple copies of chromosome 22 may be better evaluated
      by two-color FISH. This is the first use on FS biopsy material of a single probe
      for EWS, capable of detecting all known EWS rearrangements, in ES and other
      tumors. Utilization of this ancillary technique on FS for ES/pPNET and other
      tumors with distinctive chromosomal translocation is highly specific, reliable,
      expeditious (24-36 hours) and cost-effective.

PMID- 10078923
TI  - Sampling of grossly benign breast reexcisions: a multidisciplinary approach to
      assessing adequacy.
AB  - The widespread use of breast-conserving therapy in the treatment of early-stage
      breast cancer has resulted in increasing numbers of reexcision specimens
      requiring histologic assessment for residual disease and margin status. Because
      many reexcisions are performed for only microscopically positive or close
      margins, reexcision specimens often appear grossly negative and directed tissue
      sampling cannot be performed. The issue of adequate sampling in these specimens
      has not been addressed in the literature. A multidisciplinary approach to
      identifying the clinically important lesions in breast reexcisions and a cost
      effective approach to tissue sampling are needed. We reviewed 97 consecutive
      cases of grossly negative breast reexcisions in which all tissue had been
      embedded. Forty-seven specimens contained residual invasive or in situ carcinoma
      and 50 were histologically negative. Detailed histologic findings were presented
      to a medical oncologist, a radiation oncologist, and a surgeon, who assessed the
      clinical impact of each diagnosis. Of the 47 positive specimens, 30 resulted in a
      major change in patient management (recommendation for additional surgery), 10
      resulted in minor changes (alteration in radiation dose or adjuvant chemotherapy
      regimen), and 7 did not alter management. A total of 1867 blocks were submitted.
      If one block per centimeter of maximal tissue dimension had been submitted and
      the remainder of the specimen examined only if initial sections revealed invasive
      or in situ carcinoma, then 901 blocks would have been processed (52% reduction),
      but we would have missed an average of 3.7 cases resulting in a major change in
      therapy, and 3.3 cases resulting in a minor change. In contrast, two blocks per
      centimeter would have missed an average of less than one case each of diagnoses
      resulting in major and minor therapy changes (0.9 and 0.8 cases, respectively),
      and 315 (17%) fewer tissue blocks would have been processed. We recommend
      submitting two blocks per centimeter in grossly benign reexcisions, and examining
      the remainder of the tissue only if carcinoma is detected on initial sections.

PMID- 10078924
TI  - Comparison of mutations of Ki-RAS and p53 immunoreactivity in borderline and
      malignant epithelial ovarian tumors.
AB  - Ovarian tumors of low malignant potential ("borderline tumors") have been
      proposed variably to represent a distinctive type of malignancy, precursors of
      frank ovarian malignancy, or a nonmalignant process. We analyzed 81 malignant and
      39 borderline ovarian tumors for p53 immunoreactivity and alterations in codon 12
      of Ki-RAS in order to correlate these alterations with tumor and cell type.
      Diffuse p53 immunoreactivity was significantly more prevalent among malignant (36
      of 81, 44%) than among borderline (3 of 39, 8%) tumors and was particularly
      prevalent among serous invasive carcinomas (16 of 26, 62%). Conversely, mutations
      in codon 12 of Ki-RAS were significantly more prevalent in borderline (16 of 39,
      41%) than in malignant (9 of 81, 11%) ovarian tumors and were most prevalent
      among mucinous tumors. This preliminary molecular analysis suggests that serous
      borderline tumors have some molecular features usually associated with malignancy
      but are unlikely to represent a precursor of invasive serous carcinoma. In
      contrast, mucinous borderline tumors may represent a precursor or variant of
      mucinous carcinoma of the ovary.

PMID- 10078925
TI  - Is calcifying fibrous pseudotumor a late sclerosing stage of inflammatory
      myofibroblastic tumor?
AB  - Calcifying fibrous pseudotumor is a recently described distinctive lesion,
      characterized by the presence of abundant hyalinized collagen with psammomatous
      or dystrophic calcifications and a lymphoplasmacytic infiltrate. The cause and
      pathogenesis are unclear, but a possible relationship with other pseudotumors,
      like nodular fasciitis or inflammatory myofibroblastic tumor, has been proposed
      by some authors. However, cases with overlapping histologic features have not
      been reported. A 17-year-old girl with multiple peritoneal calcifying fibrous
      pseudotumors and inflammatory myofibroblastic tumors (inflammatory pseudotumors)
      is described. Some multinodular lesions showed calcifying fibrous pseudotumors
      next to inflammatory myofibroblastic tumors. Transitional stages between
      calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor were also
      present. This case clearly illustrates a histogenetic relationship between
      calcifying fibrous pseudotumor and inflammatory myofibroblastic tumor, and it
      suggests that calcifying fibrous pseudotumor is a late sclerosing stage of
      inflammatory myofibroblastic tumor, at least in some cases.

PMID- 10078926
TI  - Morules with biotin-containing optically clear nuclei in colonic tubular adenoma.
AB  - Morules have been reported in pulmonary endodermal tumors (PET) resembling fetal
      lung, in thyroid carcinoma, and in endometrial and colonic neoplasms. A morule
      has biotin-containing optically clear nuclei (OCN) in PET and thyroid carcinoma.
      Biotin-containing OCN have been also reported in endometrial tissue during
      pregnancy and in endometrioid carcinoma of the ovary, and it has been postulated
      that morules or OCN develop under the influence of female sex hormones. The
      authors report here the first case, to their knowledge, of morules with OCN in a
      colonic adenoma from a 68-year-old man. The colonic polyp consisted of ordinary
      tubular adenomatous tissue and morules. Many cells in the morules contained OCN.
      The OCN were immunopositive for biotin and reacted with streptavidin. The
      neoplastic cells in the morules were immunopositive for oncofetal antigens. Serum
      levels of female sex hormones were within the normal range, and no cells in the
      adenoma were immunopositive for receptors for progesterone and estrogen. The
      results indicate that OCN are rich in biotin and that morules may be
      embryologically immature elements that develop independently of influence by
      female sex hormones.

PMID- 10078927
TI  - Sialoblastoma: clinicopathological/immunohistochemical study.
AB  - Sialoblastoma is an extremely rare salivary tumor diagnosed at birth or shortly
      thereafter with significant variability in histologic range and clinical course,
      so that for an individual case it may be difficult to predict the most
      appropriate therapy. We detail the case of a toddler noted to have a firm 1-2-cm
      mass in the left cheek at 21 months. Parotidectomy was performed at 26 months,
      revealing a sialoblastoma; the resection margins were positive. During the next
      10 months, the mass recurred or persisted, necessitating numerous procedures. The
      tumor was composed of basaloid cells with fine chromatin and other more mature
      cuboidal epithelial cells. Ductules and solid organoid nests with some tendency
      toward peripheral pallisading were also noted. There was no perineural invasion;
      necrosis initially was sparse but increased over time. The mitotic rate also
      increased from 6 to 7/10 high-power fields in the first resection to 20/10 high
      power fields in the last resection. Nuclear pleomorphism increased with time. The
      MiB1 proliferative index revealed a dramatic increase in the number of labeled
      nuclei: from 3 cells/10 high-power fields in the first specimen to 94 cells/10
      high-power fields for the last specimen. Cytokeratin accentuated the ductal
      structures. S-100 showed a diffuse staining pattern, with darker staining of the
      spindled myoepithelial cells. The Her-2-neu protein showed moderate cytoplasmic
      staining, whereas the p53 showed only occasional labeling of nuclei. This is the
      first case of sialoblastoma with evidence of increasing anaplasia based on
      increasing proliferative capacity. Therefore, the distinction between benign and
      malignant sialoblastomas may not be as well defined as previously thought. The
      patient's prognosis is likely to be determined by the tumor grade as well as the
      stage at presentation and the extent of resection.

PMID- 10078928
TI  - An unusual case of epithelial-myoepithelial carcinoma of the liver.
AB  - The authors present an unusual case of an epithelial-myoepithelial carcinoma of
      the liver in a 67-year-old man who was admitted for resection of a gastric
      adenocarcinoma. At operation, a 3 x 3 cm mass in the right liver lobe was also
      removed. This mass consisted of duct-like structures with dual differentiation.
      The inner layer was composed of an epithelial lining, and the outer layer
      consisted of clear cells, all unrelated to the moderately well-differentiated
      gastric adenocarcinoma. The clear cells were positive for S-100 and alpha-smooth
      muscle actin, suggesting myoepithelial origin. The mass was considered to be low
      grade epithelial-myoepithelial carcinoma. However, the patient had a history of
      an oral nodule present since childhood, resected 10 years previously. These
      slides were reviewed and revealed a mixture of clear cells and basal cells with
      squamous differentiation. In addition, there were duct-like structures with the
      two-layer pattern found in the liver tumor. This tumor had numerous mitotic
      figures and showed perineural invasion, suggesting a high grade of malignancy.
      These findings led to an interpretation of the oral tumor as also being
      epithelial-myoepithelial carcinoma, which had remained as "benign" for more than
      50 years and subsequently underwent malignant transformation. During this long
      period, liver metastases may have occurred and remained low-grade. Alternatively,
      the liver and oral tumors may have arisen separately in the foregut during
      embryologic development, remaining low-grade until malignant transformation
      occurred.

PMID- 10078929
TI  - Histogenesis of testicular primitive neuroectodermal tumor.

PMID- 10078930
TI  - Malignant epithelioid angiomyolipoma.

PMID- 10078931
TI  - Malignant epithelioid angiomyolipoma.

PMID- 10078932
TI  - TGF-alpha and angiogenesis.

PMID- 10078933
TI  - Rosai-Dorfman's disease of the breast.

PMID- 10078934
TI  - Inhibition of ultraviolet B--induced c-fos gene expression and p38 mitogen
      activated protein kinase activation by (-)-epigallocatechin gallate in a human
      keratinocyte cell line.
AB  - (-)-Epigallocatechin gallate (EGCG), the major polyphenol isolated from green
      tea, is an active chemoprevention agent against cancer. However, the molecular
      mechanisms that underlie the inhibitory effects of EGCG are not well understood.
      In this study, we tested the effects of EGCG on ultraviolet (UV) B radiation
      induced c-fos gene expression in a human keratinocyte cell line, HaCaT. EGCG
      inhibited UVB-induced steady-state message and transcriptional activation of the
      c-fos gene in a dose-dependent manner. Western analyses further indicated that
      EGCG had an inhibitory effect on UVB-induced accumulation of the c-fos protein
      within the same dose range. To further examine the mechanism by which EGCG
      inhibits UVB-induced c-fos expression, we tested the effect of EGCG on upstream
      activators of the c-fos gene. We found that EGCG significantly inhibited
      activation of p38 mitogen-activated protein kinase but not c-jun NH2-terminal
      kinase or extracellular signal-regulated protein kinase activation. Our previous
      studies have indicated that UVB-induced c-fos expression may play a key role in
      UVB-induced activation of the activator protein-1 transcription factor and EGCG
      inhibited, UVB-induced activation of AP-1 in HaCaT cells. Because AP-1 is
      important for tumor promotion and c-fos is a major component of AP-1, the
      inhibitory effects of EGCG on c-fos expression may further explain the anti-tumor
      promoting effects of EGCG.

PMID- 10078935
TI  - Methylation of selected CpGs in the human O6-methylguanine-DNA methyltransferase
      promoter region as a marker of gene silencing.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) is a major determinant of
      susceptibility to methylating carcinogens and of tumor resistance to anticancer
      methylating and chloroethylating drugs. The silencing of MGMT expression that
      occurs in 20-30% of human tumor lines is tightly linked to methylation within the
      MGMTgene 5'CpG island. Previous studies on a very limited number of cell lines
      showed that such methylation was uneven, with hot-spots where methylation almost
      invariably occurred and intervening regions with very low incidences of
      methylation. To ascertain if such hot-spot methylation is in fact a ubiquitous
      hallmark of MGMT-silenced cells, we determined the methylation status of selected
      hot-spot CpGs in an extensive panel of MGMT-expressing and -silenced cell lines
      and xenografts. Using two simple and rapid bisulfite-polymerase chain reaction
      based assays, we confirmed that in MGMT-silenced cells, methylation occurred at
      these sites whereas it was essentially absent in MGMT-expressing cells.

PMID- 10078936
TI  - A specific CpG methylation pattern of the MGMT promoter region associated with
      reduced MGMT expression in primary colorectal cancers.
AB  - The enzyme O6-methylguanine-DNA methyltransferase (MGMT) protects cells from the
      cytotoxic and mutagenic effects of alkylating agents. Approximately 20% of tumor
      cell lines lack MGMT activity and are highly sensitive to alkylating agents. In
      established cancer cell lines, MGMT expression appears to be correlated with
      methylation of residues in both the promoter and the body of the gene. The effect
      of methylation of the MGMT promoter on gene expression and carcinogenesis in
      primary tumors is unknown. We investigated methylation of the MGMT promoter
      region in primary colorectal cancers and normal colonic mucosa. We used five
      methylation-sensitive restriction enzymes (BssHII, SacII, Eagl, Nael, and Smal)
      and Southern blot analysis to assess methylation in 46 cancers and 22 controls.
      Methylation of Eagl and Nael sites was seen in 12 tumors but in none of the 22
      normal colorectal mucosa specimens. This difference was statistically significant
      (P<0.01). Methylation-sensitive single-nucleotide primer extension analysis of
      four additional cytosine residues confirmed methylation of the promoter region in
      the tumors identified by Eagl and Nael digestions and served to further
      quantitate the extent of methylation. Western blot analysis of 21 tumors revealed
      statistically significant lower MGMT expression in the eight tumors with
      methylation of the Eagl and Nael sites and nt -128 than in the 13 tumors lacking
      the methylation pattern (P<0.05). MGMT activity was lower in tumors with
      methylation than in tumors that were not methylated. The difference was not,
      however, statistically significant. We conclude that a subset of colorectal
      tumors is characterized by a specific methylation pattern in the MGMT promoter
      associated with reduced MGMT expression.

PMID- 10078937
TI  - Inhibition of tenascin-C expression in mammary epithelial cells by thyroid
      hormone.
AB  - Multiple data suggest a relationship between thyroid hormone (triiodothyronine
      (T3)) and carcinogenesis. Studies on breast cancer have been inconclusive,
      suggesting contradictory effects of thyroid status and diseases. Recently, we
      reported that expression of the extracellular matrix glycoprotein tenascin-C is
      modulated by T3 during rat brain development. Because tenascin-C has been
      reported to have growth-, motility-, and angiogenic-promoting activities and to
      become upregulated during tumorigenesis in breast carcinoma and stromal cells, we
      analyzed the effects of T3 on tenascin-C expression in mammary epithelial cells.
      In this study, we showed that tenascin-C RNA expression was inhibited by T3 in
      normal un-transformed EpH4 mouse mammary epithelial cells expressing appropriate
      receptors. T3's action appeared to be due to a decreased half-life of the
      tenascin-C mRNA, with a maximum effect (85% at 100 nM) 48 h after addition. T3
      also downregulated tenascin-C in the human mammary tumor cell line SKBR-3, which
      expresses endogenous thyroid receptors. Immunoprecipitation experiments confirmed
      that tenascin-C protein content was also decreased by T3 in EpH4 cells (70%
      reduction at 100 nM). Dexamethasone had a similar inhibitory effect (70% at 100
      nM), whereas estradiol, the antiestrogen ICI 164,384, progesterone, and all-trans
      retinoic acid did not alter tenascin-C expression. Our data demonstrate an
      inhibitory action of T3 on tenascin-C expression in mammary epithelial cells that
      may play a role in the physiological regulation of this gene and in neoplastic
      processes.

PMID- 10078938
TI  - Constitutive expression of 8-lipoxygenase in papillomas and clastogenic effects
      of lipoxygenase-derived arachidonic acid metabolites in keratinocytes.
AB  - The expression pattern, enzymatic activity, and products of 8-lipoxygenase (LOX)
      were analyzed in normal and neoplastic skin of NMRI mice. While barely detectable
      in normal epidermis, 8-LOX was transiently induced by 12-O-tetradecanoylphorbol
      13-acetate and constitutively expressed in papillomas but not carcinomas obtained
      by the initiation-promotion protocol of mouse skin carcinogenesis. The product
      profile and chirality of both the native and the recombinant protein produced the
      S enantiomers of 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid (8-HETE) and 9
      hydroxy-10E,12Z-octadecadienoic acid (9-HODE) as the main arachidonic acid- and
      linoleic acid-derived metabolites. As compared with normal epidermis, papillomas
      exhibited 25- and 4-fold elevated levels of 8-HETE and 9-HODE, respectively.
      However, the varying S to R ratios of 8-HETE and the predominance of 9(R)-HODE
      indicated that in addition to 8(S)-LOX, other enzymes yet to be defined may be
      involved in 8-HETE and 9-HODE production. The massive accumulation of both 8-HETE
      and 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE) point to a critical
      role of these LOX pathways in epidermal tumor development, in particular in the
      papilloma stage. Here we showed that 8- and 12-hydroperoxyeicosatetraenoic acids
      and 8- and 12-HETE induce chromosomal alterations in cycling primary basal
      keratinocytes.

PMID- 10078939
TI  - Microsatellite instability during the immortalization and transformation of human
      breast epithelial cells in vitro.
AB  - The objective of this study was to determine whether microsatellite instability
      (MSI) and loss of heterozygosity (LOH) are involved in the immortalization of
      human breast epithelial cells (HBECs) in vitro and in the early stages of their
      transformation by benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA).
      We performed a genome-wide analysis of a total of 466 microsatellite DNA
      polymorphism loci along the X chromosome and the 22 pairs of human autosomes. MSI
      was found in the immortalized MCF-10F cells at the following loci: D11S1392 (on
      chromosome 11p13) and D17S849 (at 17p13.3), D17S796 (at 17p13.1), D17S513 (at
      17p13.1), TP53 (at 17p13.1), D17S786 (at 17p13.1), and D17S520 (at 17p12) on
      chromosome 17. The BP-transformed cells exhibited MSI in the same loci and also
      in locus D11S912 (at 11q25). The more transformed BP1E cells also exhibited MSI
      on chromosome 13q12-13 at D13S260 and D13S289, markers known to flank the breast
      cancer susceptibility gene BRCA2. In the DMBA-transformed D3 and D3-1 cells, MSI
      was observed at the locus D13S260 in addition to the previously reported locus
      D16S285 (at 16q12.1). No LOH was observed on any of the chromosomes tested in
      these cells. These observations led us to conclude that the immortalization and
      transformation of HBECs may involve defects in mechanisms responsible for the
      cell's genomic stability, such as DNA replication and DNA mismatch repair.

PMID- 10078940
TI  - Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's
      adenocarcinoma cell lines.
AB  - Barrett's metaplasia consists of columnar epithelium that replaces the normal
      esophageal mucosa in patients with chronic gastroesophageal reflux. Because
      intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma
      development, understanding the mechanisms that predispose the esophageal mucosa
      to malignant degeneration is clinically important. Glutathione s-transferase
      (GST)-pi belongs to a class of protective enzymes whose activity has been shown
      to be much lower in Barrett's metaplasia than in the normal esophagus, where this
      form of GST is predominant. In the studies described here, using
      immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi
      protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern
      blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia
      than in normal esophagus or adenocarcinomas from the same patients. Using as
      model systems three Barrett's adenocarcinoma cell lines and short-term organ
      culture of freshly resected normal esophagus and Barrett's metaplasia, dose
      dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole
      and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold
      with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM
      dexamethasone after 24 h. These studies demonstrate the ability to induce
      protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future
      chemoprevention studies in patients with this type of epithelium, which is at
      high risk for malignant degeneration.

PMID- 10078941
TI  - Identification of intestinal-type Barrett's metaplasia by using the intestine
      specific protein villin and esophageal brush cytology.
AB  - Villin is an actin-binding cytoskeletal protein required for brush-border
      formation in the normal small intestinal and renal proximal tubule epithelium.
      Villin is a marker of cell differentiation in small intestinal and renal cell
      lineages, and recent studies have shown villin to be highly expressed in 100% of
      intestinal-type Barrett's metaplasias. This epithelium is the single greatest
      risk factor for developing esophageal adenocarcinoma and arises when the normal
      esophageal squamous epithelium is replaced by a small intestine-like columnar
      epithelium after damage by chronic gastroesophageal reflux. In intestinal-type
      Barrett's metaplasia, the villin protein exhibits a highly characteristic
      staining pattern in which strong apical, brush-border staining of columnar
      epithelial cells is observed. In this study, the ability to identify intestinal
      metaplastic cells by using this distinct villin staining pattern was examined in
      endoscopic esophageal brushings from patients with confirmed Barrett's
      metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's
      metaplasia demonstrated individual columnar cells with the characteristic villin
      staining pattern, whereas all normal esophageal squamous cells, blood cells, and
      gastric columnar cells were negative for villin expression. Northern blot
      analysis demonstrated villin mRNA expression in Barrett's metaplasia but not in
      the normal squamous esophagus or gastric mucosa from the same patients. The
      combined use of villin immunohistochemical analysis and esophageal brush cytology
      may provide a simple and effective method of detecting intestinal-type Barrett's
      metaplasia in patients at higher risk for developing this epithelium, such as
      those experiencing chronic gastroesophageal reflux symptoms.

PMID- 10078942
TI  - Telomeric lengths and telomerase activity in liposarcomas.
AB  - To assess the role of telomerase in the development of liposarcomas, we measured
      telomerase activity in 36 malignant and seven benign lipomatous neoplasias from
      34 patients. A sensitive polymerase chain reaction-based telomerase assay (the
      telomeric repeat amplification protocol) was applied. Shortening or elongation of
      telomeric repeat fragment lengths, as measured by using hybridization with a
      telomere-specific oligonucleotide probe, was correlated with the presence of
      telomerase activity. The latter was demonstrable in 69% of malignant tumors.
      Benign tumors can be distinguished from malignant neoplasias on the basis of
      telomerase activity. However, telomerase expression seems to be characteristic of
      poorly differentiated liposarcomas. Myxoid/round cell liposarcomas exhibited a
      higher telomerase activity level than the classical low-grade variants.
      Telomerase activity was not correlated with age at the time of diagnosis or with
      sex. In most cases, telomerase-positive tumors showed higher proliferation
      indices than did neoplasias lacking telomerase. All eight recurrences expressed
      telomerase activity, reflecting a close association of telomerase with the
      biological behavior of liposarcomas. Our findings suggest that telomerase may
      play a key role in the establishment and progression of malignant lipomatous
      tumors.

PMID- 10078943
TI  - Lumbosacral instrumented fusion: analysis of 124 consecutive cases.
AB  - One hundred twenty-four cases of lumbosacral fusion receiving transpedicular
      screw fixation were divided into two groups and reviewed retrospectively. The
      conditions treated include spondylolisthesis, scoliosis, tumor, trauma, and
      degenerative disc disease. There were 83 males and 41 females in this consecutive
      series averaging a 45.2-month follow-up. The primary or first-time arthrodesis
      rate was 91.9%. A learning curve effect as it relates to operative time but not
      pedicular screw placement was shown. Instrumentation-related and general medical
      and surgical complications were low. Infection rates were also low; superficial
      2.4%, deep 1.6%. Nonunion or delayed union was salvaged in 10 cases, improving
      the overall fusion rate to 97.6%. The results of this study support the use of
      lumbosacral transpedicular screw fixation in select spinal conditions.

PMID- 10078944
TI  - Operative repair of symptomatic spondylolysis following a positive response to
      diagnostic pars injection.
AB  - From 1989 to 1996, 275 patients (245 male and 20 female) with back pain symptoms
      and spondylolysis of the lumbar spine were reviewed. All patients were evaluated
      by a protocol that included nonoperative treatment, bone scan, and pars
      injection. Only those whose symptoms failed nonoperative measures, showing
      negative bone scan and positive pars injection, were regarded as candidates for
      surgical management. Pars injection with Marcaine was done, and there were 93
      cases with a positive response of reproducing symptoms and symptom relief.
      Patients then received autogenous bone grafting and internal fixation of the pars
      interarticularis defect. The internal fixation devices used included translaminar
      screws (AO 3.5 cancellous screw) for the most frequent level of L5, hook screws
      for levels above L4, and augmentation with wire for cases with concomitant spinal
      bifida occulta. The average age of the surgical group (85 male and 8 female) was
      23 years (range: 19-35 years). After a follow-up averaging 30.4 months (range: 24
      48 months), fusion results were 87%. Clinical results of 85 cases (91.3%) were
      excellent to good; 8 cases were fair; there were no poor cases. Direct repair of
      the pars defect by internal fixation and bone grafting was done to preserve
      involved motion segment and to prevent abnormal stresses at adjacent levels.
      These procedures seemed to be clinically effective.

PMID- 10078945
TI  - Anterior debridement, fusion, and extrafocal stabilization in the treatment of
      osteomyelitis of the spine.
AB  - To simplify and shorten the rehabilitation after anterior debridement and fusion
      in pyogenic and tuberculous osteomyelitis of the spine, the role of additional
      extrafocal dorsal transpedicular instrumentation was studied. Thirty-three (10
      female, 23 male) patients were followed up in a prospective study and controlled
      with an average follow-up period of 22.1 months after the operation with clinical
      and neurologic check-up, blood test, and serial radiographs. Solid bony fusion
      and healing of the infection was achieved in all patients. Preoperative
      deformities could be corrected, and there were no life-threatening complications.
      Dorsal extrafocal stabilization offered the advantage of braceless rehabilitation
      without adding unpredictable risks.

PMID- 10078946
TI  - Comparative study of the incidence and severity of degenerative change in the
      transition zones after instrumented versus noninstrumented fusions of the lumbar
      spine.
AB  - The purpose of this study was to determine whether the addition of pedicle screws
      and rods to a fusion of two or more vertebrae of the lowest three motion segments
      of the lumbar spine increases the incidence or severity of transition zone change
      (TZC) above or below the fused area. A study group of 52 patients who had a
      fusion with fixation and a control group of 31 who had a nearly identical
      operation but without fixation were obtained. Radiographs and computed tomography
      scans of the area of study were taken preoperatively and were repeated
      approximately 7 years after the operation. Results showed that the addition of
      pedicle screw fixation does not increase the incidence or severity of TZC in the
      first 7 years after surgery.

PMID- 10078947
TI  - Uninstrumented posterolateral lumbar fusion for single level isolated disc
      resorption and/or degenerative disc disease.
AB  - The limited soft-tissue envelope technique for an uninstrumented single-level
      posterolateral lumbar fusion has been studied in a group of 23 patients. It
      resulted in a solid fusion in 21 of 23 (91%) patients. Overall, 18 of 23 (78%)
      patients had a satisfactory outcome to this fusion technique, which can be
      performed in any community-based hospital.

PMID- 10078948
TI  - Usefulness of Posner's definition of spinal instability for selection of surgical
      treatment for lumbar spinal stenosis.
AB  - The aim of this study was to determine the usefulness of Posner's definition of
      spinal instability for selection of surgical therapy for lumbar spinal stenosis.
      Sixty patients with lumbar spinal stenosis were studied. Thirty-three patients
      were found to have instability, as defined using Posner's method. Nineteen of the
      33 patients with instability underwent decompression and instrumented fusion. The
      14 remaining patients with instability underwent decompression alone. Twenty
      seven patients without instability were treated by decompression alone. Patients
      treated by decompression and fusion obtained the best results. Good results also
      could be obtained by decompression alone only if patients did not have
      instability. However, patients treated by decompression alone in the presence of
      instability had the worst results. The Posner's definition of instability proved
      useful for selecting patients with instability for fusion treatment.

PMID- 10078949
TI  - Anterior cervical graft and plate load sharing.
AB  - Anterior discectomy and fusion with an interbody bone graft and anterior plate is
      a common procedure in cervical spine surgical management. However, the graft may
      be shielded from some mechanical loading by the plate. Mechanical testing was
      performed on six cadaveric calf spines that were subjected to a simulated
      anterior cervical discectomy and fusion with an interbody bone graft alone and
      with an anterior plate to determine the amount of load sharing between the graft
      and plate. The load-displacement data were used to compute the amount of load
      sharing between the graft and the plate as a continuous function of the applied
      axial compression load. Although the percent load transmitted through the graft
      decreased (53 to 41%) as the axial load increased (45 to 90 N), the magnitude of
      load transmitted through the graft increased (24 to 37 N), with corresponding
      intervertebral strains <6%. In a single-level procedure, an anterior cervical
      plate serves as a load-sharing device rather than a load-shielding device,
      enabling graft consolidation as observed in clinical studies.

PMID- 10078950
TI  - Axial symptoms and cervical alignments after cervical anterior spinal fusion for
      patients with cervical myelopathy.
AB  - This retrospective clinical study was designed to examine the relation between
      cervical alignment and axial symptoms developing after cervical anterior spinal
      fusion. Sixty patients with myelopathy treated with cervical anterior spinal
      fusion were reviewed. For radiographic evaluation, lordosis, enlargement of the
      fused segments and neural foramen, radiographic union, and degeneration of
      adjacent segment were reviewed before or after surgery or both. Twenty-three
      patients had axial symptoms. Only local kyphosis and narrowing of the neural
      foramen at the fused segment were recognized more often in patients with axial
      symptoms than in those without such symptoms. No less than 2 mm and < or = 5 mm
      in enlargement of the anterior disc space immediately after surgery resulted in
      maintenance of cervical lordosis. These findings suggest that > or = 2 mm and <
      or = 5 mm in enlargement of anterior vertebral body height during operation
      results in prevention of axial symptoms.

PMID- 10078951
TI  - Proliferation potential of human lumbar disc after herniation.
AB  - To investigate the regenerative potential of human disc tissue, the disc samples
      were obtained during surgery from 24 adult patients with first lumbar prolapses
      and from 14 patients with recurrent lumbar prolapses. Preoperative magnetic
      resonance imaging (MRI) confirmed prolapse and disc degeneration in all cases.
      The proliferation activity of the sampled connective tissue cells was studied
      with the immunohistochemical expression of Ki-67(MIB-1) antigen. The antigen was
      positive in 6 of 24 (25%) specimens from first prolapse and in none of the 14
      specimens from the recurrent prolapse. The amount of proliferative cells did not
      correlate to the degree of disc degeneration in MRI. Our results indicate that
      connective tissue cells in adult degenerative disc may show proliferation
      activity after the first herniation and thus regenerative potential. The enhanced
      matrix proliferation may not be a significant reason for recurrent prolapses
      because none of the recurrent disc specimen showed proliferation activity.

PMID- 10078952
TI  - Asymmetry of paraspinal EMG-time characteristics in idiopathic scoliosis.
AB  - The purpose of this study was to investigate the activation pattern of the
      paraspinal muscles in scoliotic and normal subjects. Force-time and
      electromyography (EMG)-time curves of paraspinal muscles were recorded during
      maximal isometric trunk extensions in 15 girls with adolescent idiopathic
      scoliosis (AIS) and in 14 healthy girls with structurally normal spines. The
      isometric force-time curves as well as the maximal integrated electromyography
      (IEMG) activities that were recorded from both sides of the thoracic and lumbar
      spine did not show any significant differences between the two subject groups.
      However, in the subjects with AIS, the IEMG activities recorded at the onset and
      during the early (submaximal) phases of muscle contraction were significantly
      higher in the left lumbar muscles compared with the right side. The observed
      intensity-specific EMG asymmetry in the present scoliotic subjects may be
      attributed to the imbalanced neural input associated with AIS that may also have
      pathogenetic importance in the etiology of idiopathic scoliosis.

PMID- 10078953
TI  - The role of lumbar lordosis, vertebral end-plate inclination, disc height, and
      facet orientation in degenerative spondylolisthesis.
AB  - Degenerative spondylolisthesis (DS) is a common condition of the aging spine, but
      the underlying pathomechanisms remain controversial. Most previous studies
      focused on the role of facet-joint alignment and reported a pronounced sagittal
      orientation. This, however, may also be a secondary feature to the slippage. This
      study analyzed several radiologic findings in the lower lumbar spine in 23
      patients with DS (group A) and 40 age- and sex-matched controls (group B). Facet
      joint angulation, intervertebral disc height, lordosis of the lumbar spine (L1
      S1), and inclination of the L4, L5, and S1 end plates were assessed from neutral
      standing lateral radiographs and computed tomography (CT) or magnetic resonance
      imaging (MRI) investigations. Two findings were found to be significantly
      different between the groups. Facet joints were aligned more sagittal in group A,
      and the inclination of the vertebral end plates was more horizontal in group B.
      There was no statistical difference in lumbar lordosis or L4-5 disc height
      between the two groups, with disc height being decreased in both groups. In group
      A, more gliding was associated with a further decrease in disc space, pronounced
      sagittal alignment of the L4-5 facet joints, and a decrease in lumbar lordosis.
      We concluded that further studies should focus on the analysis of spinal
      alignment and lower lumbar end-plate orientation to identify patients at risk for
      development of DS.

PMID- 10078954
TI  - Shortening of a unit rod protruding into the hip joint: case report and
      description of a surgical technique.
AB  - A unit rod is a well-accepted method of posterior spinal instrumentation in
      patients with cerebral palsy (CP). Several types of complications after the use
      of a unit rod were reported, including penetration through the medial wall of the
      pelvis. A patient who underwent anterior and posterior spinal fusion with unit
      rod instrumentation was found to have penetration of the unit rod into a
      dysplastic hip joint. The pelvic limb of the rod was shortened with a burr
      through an anterolateral approach to the iliac bone. This procedure was
      associated with a lower blood loss than was previously reported for revisions of
      unit rods. There was no need for hardware removal and therefore no loss of
      correction. The unit rod may be shortened before surgery to prevent this problem.
      The described procedure is a simple way of correcting penetration of a unit-rod
      limb into the hip joint.

PMID- 10078955
TI  - Laser-assisted diskectomy performed by an internist resulting in cauda equina
      syndrome.
AB  - An internist performed percutaneous laser-assisted diskectomies (PLADs) on a
      patient with a sequestrated disc and stenosis. Subspecialists who perform PLADs
      should be trained in patient selection and lumbar diskectomy techniques.
      Chymopapain, percutaneous nucleotome-assisted diskectomy, and PLADs are
      alternatives to microdiskectomy for the management of lumbar disc herniations.
      PLADs were performed at the L4-5/L5-S1 levels in a 38-year-old woman with
      magnetic resonance (MR)-documented L4-5 stenosis and disc disease. After PLADs,
      she developed a subacute cauda equina syndrome. Two months later, a neurosurgeon
      performed an L4-5 coronal hemilaminectomy with diskectomy. Within 6 postoperative
      weeks, she was neurologically intact. Only specialists trained in the selection,
      neurodiagnostic, and surgical management of lumbar disc disease should perform
      PLADs.

PMID- 10078956
TI  - Decompression in the surgical management of degenerative spondylolisthesis:
      advantages of a conservative approach in 290 patients.

PMID- 10078957
TI  - Cervical rheumatoid arthritis subluxations without myelopathy.

PMID- 10078958
TI  - Beta-galactosidase marker genes to tag and track human hematopoietic cells.

PMID- 10078959
TI  - Selective delivery of herpes virus vectors to experimental brain tumors using RMP
      7.
AB  - RMP-7, a bradykinin analog, has been shown to selectively open the blood-tumor
      barrier for the delivery of chemotherapeutic drugs to brain tumors. In contrast
      to bradykinin, RMP-7 has no hypotensive effects and has been approved for human
      use. This study was initiated to determine whether RMP-7 would open the blood
      tumor barrier to virus vectors encoding tumor-killing genes in an experimental
      model. The herpes virus vector used, hrR3, which encodes virus thymidine kinase
      gene and the lacZ reporter gene, is defective in a gene encoding ribonucleotide
      reductase, replicates selectively in dividing tumor cells and not in postmitotic
      neural cells. It was determined that an optimum dose of RMP-7 (1.5-3.0 microg/kg
      over 10-15 minutes) enhanced viral delivery to brain tumors in rats bearing
      intracranial 9 L gliosarcomas when infused through the carotid artery immediately
      prior to virus vector application. Maximum expression of the lacZ reporter gene
      occurred at 3 days after intracarotid infusion. By 8 days, transgene expression
      was largely confined to tumor foci away from the main tumor mass. Viral delivery
      was essentially specific to tumor cells, with little transgene expression
      elsewhere in the brain. Minimal uptake and pathology was noted in the kidney,
      spleen, and liver. These findings indicate that intracarotid delivery of RMP-7
      can augment the selective delivery of virus vectors to brain tumors in an
      experimental rat model, with the potential for application to human brain tumors.

PMID- 10078960
TI  - Complementary adenoviral vectors for oncolysis.
AB  - Replication-competent adenoviruses (Ads) were used for oncolytic virotherapy soon
      after they were discovered. Recently mutated and genetically engineered Ads have
      been shown to selectively lyse tumor cells. We have split the human Ad type 5
      genome into two defective viruses that complement each other only in certain
      tumor cells. The genome of one of these vectors, GT5610, contains only the
      minimal viral elements required in cis for replication and packaging and the E1
      viral genes with E1A under the control of the human alpha-fetoprotein promoter.
      This "controlled" vector has a capacity for 30 kilobases of foreign DNA. The
      supplemental vector, AdHbeta, contains all adenoviral genes except for E1. Both
      vectors were designed to carry heterologous reporter genes whose expression could
      be detected throughout the tumor. Coinfection of hepatocarcinoma cells that have
      the capacity to transcribe genes under the control of the alpha-fetoprotein
      promoter leads to cell lysis and copropagation. The oncolytic spread of these
      complementary vectors in vivo was demonstrated by the intratumoral injection of
      human hepatocarcinomas xenografted in severe combined immunodeficient (SCID)
      mice. This system presents safety and gene capacity features that could yield a
      therapeutic advantage over oncolysis by a single virus.

PMID- 10078961
TI  - Preclinical development of human granulocyte-macrophage colony-stimulating factor
      transfected melanoma cell vaccine using established canine cell lines and normal
      dogs.
AB  - Tumor vaccines and gene therapy have received significant attention as means of
      increasing cellular and humoral immune responses to cancer. We conducted a pilot
      study of seven research dogs to determine whether intradermal injection of canine
      tumor cells transfected via the Accell particle-mediated gene transfer device
      with the cDNA for human granulocyte-macrophage colony-stimulating factor (hGM
      CSF) would generate biologically relevant levels of protein and result in
      demonstrable histological changes at sites of vaccination. Tumor cell vaccines of
      10(7) irradiated canine melanoma cells were nontoxic, safe, and well tolerated.
      No significant alterations in blood chemistry values or hematological profiles
      were detected. A histological review of control vaccine sites revealed
      inflammatory responses predominated by eosinophils, whereas vaccine sites with
      hGM-CSF-transfected tumor cells had an influx of neutrophils and macrophages.
      Enzyme-linked immunosorbent assays of skin biopsies from vaccine sites had local
      hGM-CSF production (8.68-16.82 ng/site of injection) at 24 hours after injection
      and detectable levels (0.014-0.081 ng/site) for < or =2 weeks following
      vaccination. Flow cytometric analysis of hGM-CSF-transfected cells demonstrated <
      or =25% transfection efficiency, and hGM-CSF levels obtained during time-course
      assays demonstrated biologically relevant levels for both irradiated and
      nonirradiated samples. These data demonstrate the in vivo biological activity of
      irradiated hGM-CSF-transfected canine tumor cells and help provide evidence for a
      valid translational research model of spontaneous tumors.

PMID- 10078962
TI  - Regression of intracerebral rat glioma isografts by therapeutic subcutaneous
      immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor
      cells.
AB  - Progress in the definition of the roles of various costimulators and cytokines in
      determining the type and height of immune responses has made it important to
      explore genetically altered tumor cells expressing such molecules for therapeutic
      immunizations. We have studied the effect of therapeutic subcutaneous (s.c.)
      immunizations on the growth of preexisting intracerebral brain tumor isografts in
      the rat. Transfectant glioma cell clones expressing either rat interferon-gamma
      (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected. After
      irradiation (80 Gy) the clones were used for immunization (administered in up to
      four s.c. doses in a hind leg over 14-day intervals starting 1 day after the
      intracranial isografting of the parental tumor). Significant growth inhibition of
      the intracerebral parental tumors was induced by transfectants expressing IFN
      gamma and IL-7, respectively. The strongest effect was observed with IFN-gamma
      expressing cells, resulting in cures in 37% of the males and in 100% of the
      females. Immunization with IL-7 had a similar, strong initial effect, with
      significantly prolonged survival in the majority of the rats but a lower final
      cure rate (survival for >150 days). The B7-1-expressing tumor clones induced
      cures in seven of eight female rats; however, no cures were seen in the male
      rats. It was also shown that the B7-1-expressing cells were themselves strongly
      immunogenic in female rats, requiring high cell numbers to result in a
      progressively growing tumor upon s.c. isografting; this was not the case in male
      rats. As a whole, the results imply that despite the unfavorable location of
      intracerebral tumors, therapeutic s.c. immunizations with certain types of
      genetically altered tumor cells can induce complete regressions with permanent
      survival and without gross neurological or other apparent signs of brain damage.
      The present results demonstrate complete regressions when immunizations are
      initiated shortly after intracranial isografting, when the intracerebral tumor is
      small.

PMID- 10078963
TI  - Induction of antitumor immunity by direct intratumoral injection of a recombinant
      adenovirus vector expressing interleukin-12.
AB  - Direct intratumoral (i.t.) injection of adenoviruses (Ads) expressing specific
      immunostimulatory cytokines represents an attractive strategy for the clinical
      implementation of cytokine gene therapy of cancer. Interleukin-12 (IL-12) is a
      heterodimeric cytokine produced by antigen-presenting cells and promotes a T
      helper 1-like immune response. We have constructed an Ad vector (AdCMV-mIL-12)
      containing both chains of the murine IL-12 (mIL-12) gene linked by an internal
      ribosomal entry site sequence under the transcriptional control of the
      cytomegalovirus immediate-early gene promoter, which is able to mediate the
      transient expression of very high levels of biologically active mIL-12 both in
      vitro and in vivo. An i.t. injection of 4x10(8) plaque-forming units of AdCMV-mIL
      12 resulted in a complete regression of day 7 established subcutaneous MC38
      murine adenocarcinomas and MCA205 murine fibrosarcomas. Treated animals rejected
      a subsequent rechallenge with MC38 and MCA205, respectively, demonstrating the
      induction of long-lasting antitumor immunity. Specific antitumor cytotoxic T
      lymphocyte reactivity was detected in splenocytes harvested from treated animals.
      A significant increase in the numbers of both CD4+ and CD8+ T cells in the AdCMV
      mIL-12-infected tumors was observed. Ad-mediated IL-12 gene therapy was also
      associated with measurable serum levels of mIL-12 and profound changes in the
      composition of splenic lymphocytes. Taken together, these results demonstrate the
      feasibility and efficacy of delivering IL-12 directly i.t. using a recombinant
      adenoviral vector.

PMID- 10078964
TI  - Cooperative therapeutic effects of androgen ablation and adenovirus-mediated
      herpes simplex virus thymidine kinase gene and ganciclovir therapy in
      experimental prostate cancer.
AB  - Adenovirus-mediated transduction of the herpes simplex thymidine kinase gene (HSV
      tk) in conjunction with ganciclovir (GCV) has been shown to result in significant
      growth suppression and to enhance survival in a model of mouse prostate cancer.
      However, this therapeutic activity is not sustained, because in most cases tumors
      eventually regrow and ultimately cause the death of the host. Androgen ablation,
      an inducer of apoptosis in prostate cells which is used widely as palliative
      therapy in patients with prostate cancer, was combined with HSV-tk plus GCV using
      an androgen-sensitive mouse prostate cancer cell line. The combination of
      castration and HSV-tk plus GCV led to markedly enhanced tumor growth suppression
      in both subcutaneous and orthotopic models compared with either treatment alone
      and resulted in an enhanced survival in which combination-treated animals lived
      twice as long as controls in the subcutaneous model and over 50% longer than
      controls in the orthotopic model. Further analysis of apoptotic activity
      demonstrated high levels of apoptosis only in combined androgen ablation and HSV
      tk plus GCV-treated tumors after 14 days of growth in an androgen-depleted
      environment and 8 days after HSV-tk plus GCV therapy. At this time, the apoptotic
      index, but not the percent of necrotic tissue, was significantly higher for
      combination therapy-treated tumors relative to control-treated tumors or either
      treatment alone. These data indicate that the therapeutic effects of androgen
      ablation and HSV-tk plus GCV are cooperative and that increased apoptosis may, in
      part, underlie these activities.

PMID- 10078965
TI  - Delivery of adenoviral vectors to the prostate for gene therapy.
AB  - Prostate cancer has become the most frequently occurring cancer and the second
      leading cause of cancer deaths in men. One novel approach to combat prostate
      cancer is gene therapy. A replication-deficient recombinant adenoviral vector
      (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) (lacZ) under the
      control of the Rous sarcoma virus promoter was used to determine which delivery
      route was best for the transduction of adenoviral vectors to the prostate. Using
      a canine model, adenoviral vectors were administered by intravenous, intra
      arterial, and intraprostatic (i.p.) injections. After injections, the expression
      of the lacZ gene was measured in canine prostates as well as in various other
      organs to determine the distribution of the disseminated adenoviral vector by (a)
      the percentage of cells expressing lacZ in situ (5-bromo-4-chloro-3-indolyl beta
      D-galactoside staining), (b) beta-gal enzymatic activity (colorimetric beta-gal
      assay), and (c) polymerase chain reaction of genomic DNA using primers specific
      for the adenoviral genome. An i.p. injection of the adenoviral vector resulted in
      a greater transduction rate and expression level of lacZ in the prostate than
      either intravenous or intra-arterial (inferior vesical/prostatic artery)
      injections. Thus, an i.p. (or intratumoral) injection seems to be the best route
      to treat local regional prostate cancer by viral-based gene therapy.

PMID- 10078966
TI  - Induction of tumor antigen-specific immunity using plasmid DNA immunization in
      mice.
AB  - We have evaluated the ability of bioballistic "gene gun" immunization of mice
      with plasmid DNA encoding clinically relevant tumor antigens to induce protective
      antitumor immunity. Mice immunized with plasmid cDNA encoding the cervical
      carcinoma-associated human papillomavirus 16-E7 gene product exhibited potent
      anti-E7-specific cytotoxic T lymphocytes and were protected completely against a
      subsequent challenge with the E7+ C3 sarcoma. Of perhaps greater clinical
      interest, genetic immunization using cDNA encoding the normal, germline-encoded
      murine melanosomal protein tyrosinase-related protein-2 (TRP-2) resulted in
      delayed outgrowth of TRP-2+ B16 melanoma in mice and was associated with an in
      vivo activation of TRP-2-specific cytotoxic T lymphocytes. Codelivery of plasmid
      cDNA encoding TRP-2 and the T helper 1-biasing cytokine murine interleukin-12
      considerably enhanced the antitumor efficacy of these gene-based melanoma
      vaccines.

PMID- 10078967
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by cDNA
      transfected tumor cells induces a more potent antitumor response than exogenous
      GM-CSF.
AB  - Clinical cancer gene therapy trials have generally focused on the transfer of
      cytokine cDNA to tumor cells ex vivo and with the subsequent vaccination of the
      patient with these genetically altered tumor cells. This approach results in high
      local cytokine concentrations that may account for the efficacy of this technique
      in animal models. We hypothesized that the expression of certain cytokines by
      tumor cells would be a superior immune stimulant when compared with local
      delivery of exogenous cytokines. Granulocyte-macrophage colony-stimulating factor
      (GM-CSF) cDNA in a nonviral expression vector was inserted into MDA-MB-231 (human
      breast cancer), M21 (human melanoma), B16 (murine melanoma), and P815
      (mastocytoma) cells by particle-mediated gene transfer. The ability of
      transfected tumor cells to generate a tumor-specific immune response was
      evaluated in an in vitro mixed lymphocyte-tumor cell assay and in an in vivo
      murine tumor protection model. Peripheral blood lymphocytes cocultured with human
      GM-CSF-transfected tumor cells were 3- to 5-fold more effective at lysis of the
      parental tumor cells than were peripheral blood lymphocytes incubated with
      irradiated tumor cells and exogenous human GM-CSF. Mice immunized with murine GM
      CSF-transfected irradiated B16 murine melanoma cells or P815 mastocytoma cells
      were protected from subsequent tumor challenge, whereas mice immunized with the
      nontransfected tumors and cutaneous transfection of murine GM-CSF cDNA at the
      vaccination site developed tumors more frequently. The results indicate that GM
      CSF protein expressed in human and murine tumor cells is a superior antitumor
      immune stimulant compared with exogenous GM-CSF in the tumor microenvironment.

PMID- 10078968
TI  - Enhanced adjuvant effect of granulocyte-macrophage colony-stimulating factor plus
      interleukin-12 compared with either alone in vaccine-induced tumor immunity.
AB  - Using the poorly immunogenic D5 murine melanoma, we examined the adjuvant effect
      of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12
      (IL-12) secretion by gene-modified tumor cells inoculated as a vaccine to prime
      tumor-draining lymph nodes (TDLNs). D5 transfectants that secreted IL-12 or GM
      CSF alone were compared with a double transfectant that secreted equivalent
      amounts of both cytokines. TDLN cells harvested 9-10 days after subcutaneous
      tumor inoculation were cultured sequentially in anti-CD3 and IL-2 and assessed
      for antitumor reactivity against wild-type D5 tumor. The double transfectant
      induced TDLN effector cells had greater cytotoxicity in a long-term assay than
      TDLN cells primed by single transfectants. In adoptive immunotherapy, the TDLN
      cells primed by the double transfectant were significantly better at mediating
      the regression of established tumors compared with the TDLN cells elicited by the
      single transfectants. Both IL-12 and GM-CSF had adjuvant effects in promoting
      tumor-reactive TDLN cells, but the combination was better than either alone.
      These observations suggest that the immunomodulation roles of IL-12 and GM-CSF
      are different and complementary.

PMID- 10078969
TI  - Impaired intracellular trafficking is a common disease mechanism of PMP22 point
      mutations in peripheral neuropathies.
AB  - The most common forms of hereditary motor and sensory neuropathies (HMSN) or
      Charcot-Marie-Tooth disease (CMT) are associated with mutations affecting myelin
      genes in the peripheral nervous system. A minor subgroup of CMT type 1A (CMT1A)
      is caused by point mutations in the gene encoding the peripheral myelin protein
      22 (PMP22). To study the mechanisms by which these mutations cause the CMT
      pathology, we transiently transfected COS7 and Schwann cells with wild-type and
      PMP22 expression constructs carrying six representative dominant or de novo point
      mutations and one putative recessive point mutation. All but one of the first
      group of mutant PMP22 proteins failed to be incorporated into the plasma membrane
      and were retained in intracellular compartments of transfected cells.
      Surprisingly, the recessive PMP22 mutation produced a protein that was also
      mildly impaired in trafficking. Thus, our results suggest a common disease
      mechanism underlying the pathology of CMT1A due to PMP22 point mutations.

PMID- 10078970
TI  - Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease
      virus-infected brain is dependent upon inflammation.
AB  - Infection of immunocompetent adult rats with Borna disease virus (BDV) causes
      severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP,
      genes previously shown to be implicated in CNS disease and peripheral
      inflammation, was dramatically upregulated in the cortical neurons of acutely BDV
      infected rats. Neuronal COX-2 and CGRP upregulation was predominantly seen in
      brain areas where ED1-positive macrophages/microglia accumulated. In addition,
      COX-2 expression was strongly induced in brain endothelial cells and the number
      of COX-2 immunoreactive microglial cells was increased. In contrast, despite
      increased expression of viral antigens, neither COX-2 nor CGRP expression was
      altered in the CNS of BDV-infected rats treated with dexamethasone, or tolerant
      to BDV. Thus, increased CGRP and COX-2 expression in the BDV-infected brain is
      the result of the inflammatory response and likely to be involved in the
      pathogenesis of virus-induced encephalitis.

PMID- 10078971
TI  - A comparative study on neurochemistry of cerebrospinal fluid in advanced
      Parkinson's disease.
AB  - This study addresses two issues: (1) the comparative neurochemistry of classic
      tremor type of Parkinson's disease or PD-A and akinetic type of Parkinson's
      disease or PD-B; and (2) the neurochemistry of levodopa failure syndrome (LDFS).
      Cerebrospinal fluid from the lateral ventricle was collected from 50 patients
      with idiopathic Parkinson's disease of PD-A and PD-B. Levels of monoamine
      neurotransmitters and metabolites were determined using high performance liquid
      chromatography. We have found that (1) 5-hydroxylindoleacetic acid (5-HIAA) level
      is significantly lower in PD-B than in PD-A; (2) 5-HIAA level is inversely
      associated with score of part one of United Parkinson's Disease Rating Score
      (UPDRS); (3) 5-HIAA level is inversely associated with score of part four of
      UPDRS; (4) 3-O-methyldopa (3-OMD) level is positively associated with levodopa
      failure syndrome (LDFS) assessed by part four of UPDRS and inversely associates
      with 5-HIAA. From these data, it can be inferred that serotonergic activity is
      decreased in PD-B to a greater extent than in PD-A and that decreased
      serotonergic activity plays a role in LDFS.

PMID- 10078972
TI  - Mapping the APP/presenilin (PS) binding domains: the hydrophilic N-terminus of
      PS2 is sufficient for interaction with APP and can displace APP/PS1 interaction.
AB  - Mutations in presenilin 1 and presenilin 2 (PS1 and PS2, respectively) genes
      cause the large majority of familial forms of early-onset Alzheimer's disease.
      The physical interaction between presenilins and APP has been recently described
      using coimmunoprecipitation. With a similar technique, we confirmed this
      interaction and have mapped the interaction domains on both PS2 and APP. Using
      several carboxy-terminal truncated forms of PS2, we demonstrated that the
      hydrophilic amino terminus of PS2 (residues 1 to 87, PS2NT) was sufficient for
      interaction with APP. Interestingly, only a construct with a leader peptide for
      secretion (SecPS2NT) and not its cytosolic counterpart was shown to interact with
      APP. For APP, we could demonstrate interaction of PS2 with the last 100 but not
      the last 45 amino acids of APP, including therefore the A beta region.
      Accordingly, SecPS2NT is capable of binding to A beta-immunoreactive species in
      conditioned medium. In addition, a second region in the extracellular domain of
      APP also interacted with PS2. Comparable results with PS1 indicate that the two
      presenilins share similar determinants of binding to APP. Confirming these
      results, SecPS2NT is able to inhibit PS1/APP interaction. Such a competition
      makes it unlikely that the PS/APP interaction results from nonspecific
      aggregation of PS in transfected cells. The physical interaction of presenilins
      with a region encompassing the A beta sequence of APP could be causally related
      to the misprocessing of APP and the production of A beta1-42.

PMID- 10078973
TI  - Synaptic transmission and hippocampal long-term potentiation in transgenic mice
      expressing FAD-linked presenilin 1.
AB  - Mutations in two related genes, presenilin 1 and presenilin 2 (PS1 and PS2),
      cause a subset of early-onset familial Alzheimer's disease (FAD). PS1 is
      expressed in a variety of neuronal and peripheral tissues, including neuronal
      populations known to be at risk in Alzheimer's disease such as CA1 hippocampal
      neurons. To examine whether FAD-linked mutations in PS1 directly influence the
      physiology of learning and memory, we measured the field excitatory postsynaptic
      potential (fEPSP) at the Schaffer collateral-CA1 synapse in hippocampal slices.
      Basal synaptic transmission and long-term potentiation (LTP) were examined in
      neurons of transgenic mice expressing wild-type human PS1 (WtTg) and FAD-linked
      A246E PS1 variant (MTg) and in neurons of nontransgenic littermates (NTg).
      Several measures of basal synaptic transmission were unaltered in WtTg and MTg
      compared to NTg mice, including maximum fEPSP slope, maximum fEPSP amplitude,
      maximum fiber volley amplitude, and the function relating fiber volley amplitude
      to fEPSP slope, an index of basal synaptic strength. In addition, paired-pulse
      facilitation was not changed. However, upon theta burst stimulation or high
      frequency stimulation, input-specific LTP in MTg animals had a larger initial
      amplitude and was more persistent than that in WtTg or NTg animals. These data
      suggest that the FAD-linked A246E variant of PS1 leads to higher degree of LTP
      induction in mice.

PMID- 10078974
TI  - Sialylated human apolipoprotein E (apoEs) is preferentially associated with
      neuron-enriched cultures from APOE transgenic mice.
AB  - Mice transgenic for human APOE2, E3, and E4 alleles express native 34-kDa human
      apoE and two sialylated apoE isoproteins with approximate molecular weights of 37
      kDa (apoEs) and 39 kDa (apoEs2) in brain. These multiple apoE/apoEs/apoEs2 band
      patterns on Western blot are also observed in human brain, but are not seen in
      wild-type mouse brain. Both the 37-kDa apoEs and 39-kDa apoEs2 are coprecipitated
      with native 34-kDa apoE by antibody to human apoE. Neuraminidase digestion
      eliminates the 37- and 39-kDa forms and results in a downward shift in the bands
      to the position of the 34-kDa native form. These sialylated apoE isoproteins are
      found preferentially associated with neurons and contribute significantly (50
      60%) to the total neuronal apoE in neuronal cultures from transgenic mice, while
      only 5-10% of total apoE is sialylated in cultures enriched in glial cells. In
      situ hybridization and immunocytochemistry demonstrate apoE mRNA and apoE
      immunoreactivity are predominantly located in cell soma of neurons, not in
      neuronal processes.

PMID- 10078975
TI  - An ethnographic comparison of HIV risk behaviors among heroin and methamphetamine
      injectors.
AB  - Drug injection and other practices affecting the risk of human immunodeficiency
      virus (HIV) infection were studied among 154 heroin users and 45 methamphetamine
      users in San Antonio, Texas. Amphetamine users were younger, mostly white, and
      had less-severe drug dependence. Heroin users had significantly higher levels of
      needle risk, as indicated by frequency of injection, number of persons sharing
      equipment, and place of injection. Methamphetamine users tended to buy syringes
      in lots of 10 or more from pharmacies and to use a syringe less than 5 times
      before discarding it. Heroin users tended to buy 1 needle at a time from an
      illicit source and to use it more than 20 times. Of methamphetamine users, 71%
      had more than one sex partner, compared to 39% of heroin users. Partners of
      methamphetamine users were more likely to be drug injectors than were partners of
      heroin users. Fewer methamphetamine users reported a behavior change in response
      to the acquired immunodeficiency syndrome (AIDS) epidemic, and fewer had been
      contacted by AIDS Education/Outreach. We suggest that efforts to promote risk
      reduction among methamphetamine users be stepped up because this population has
      been underserved and because less-sweeping behavior changes are needed to reduce
      needle-related risks to acceptable levels.

PMID- 10078976
TI  - Early deviance and related risk factors in the children of narcotic addicts.
AB  - This descriptive study examines the self-reported behaviors of 285 male and
      female adolescent children (ages 12-17) of narcotic addicts participating in
      methadone maintenance programs. These children responded to an extensive 2.5-hour
      interview questionnaire focusing on current and past activities, including
      criminal activities prior to age 12. The findings revealed that early deviance,
      assessed by self-report measures of both severity and variety, is related to
      current adolescent drug and alcohol use, association with deviant peers, a
      negative view of home atmosphere, and psychological symptomatology. These results
      are contrasted with the retrospective reports of adolescent behavior obtained
      from adult male narcotic addicts in a prior study of vulnerability to addiction.
      The comparability of study results is discussed in the context of developmental
      risk factors, prevention and treatment strategies, and other considerations
      specifically related to the development of children of narcotic addicts.

PMID- 10078977
TI  - Sequences of powder cocaine and crack use among arrestees in Los Angeles County.
AB  - The epidemic of cocaine abuse has led to numerous studies on the substance. While
      extent of use, characteristics of users, patterns of use, and consequences of
      dependence are well documented for both powder cocaine and crack, few studies
      have dealt with the sequence or progression of use between the two forms of
      cocaine. This paper draws on arrestee data collected from county jails in Los
      Angeles, California. It identifies four sequences of powder cocaine and crack use
      and examines each sequence in terms of user characteristics, history of use,
      dependence, contact with the criminal justice system, and concomitant use of
      other drugs. Findings not only confirm some already established observations, but
      also offer new knowledge on powder cocaine and crack abuse. For instance, (a)
      whereas powder cocaine-initiated users are more likely to progress to crack than
      to restrict their use to powder cocaine only, crack-initiated users tend more
      often to use crack only than to progress to powder cocaine; and (b) powder
      cocaine and crack, when used interchangeably, can interact and reinforce each
      other, resulting in a higher level of use and dependence on both forms of the
      substance. This paper contributes to the understanding of powder cocaine and
      crack use among criminal offenders, in particular, and across the adult
      population, in general. It also sheds light on prevention, treatment, and social
      control policies of both cocaine abuse and overall illicit drug use.

PMID- 10078978
TI  - The autonomy of mood disorders among cocaine-using methadone patients.
AB  - This study uses an algorithm to determine whether patients dually diagnosed with
      a mood disorder and cocaine dependence have either (a) an autonomous mood
      disorder (onset of mood disorder prior to substance use disorder (SUD) or mood
      disorder symptoms persist during periods of abstinence or (b) a nonautonomous
      mood disorder (onset of SUD preceded mood disorder and mood disorder symptoms
      remit during periods of abstinence). The relationship among autonomy, patient
      characteristics, and treatment completion is examined. The sample included 67
      methadone patients with a mood disorder (87% major depression, 13% bipolar) who
      were enrolling in a 6-month psychosocial treatment for cocaine use. Of these
      subjects, 27% were rated as having an autonomous mood disorder and 73% a
      nonautonomous mood disorder. Mean age was 37 years; 55% were female and 82% were
      Hispanic or African-American. All subjects had been stabilized on methadone (mean
      = 70 mg). During the 30 days prior to study intake, subjects with an autonomous
      mood disorder, compared to subjects with a nonautonomous mood disorder, reported
      fewer days using cocaine (12.5 versus 21.1) and fewer days drinking four or more
      drinks of alcohol (1.1 versus 6. 1). Treatment completion was associated with
      less cocaine use, autonomy, and African-American ethnicity. However, when these
      variables were controlled using logistic regression, only autonomous mood
      disorder and ethnicity predicted treatment completion. These results suggest that
      autonomy may be a useful construct to measure, and that subjects with
      nonautonomous mood disorders may need special efforts to ensure treatment
      retention.

PMID- 10078979
TI  - Validity of self-report of drug use among STD patients, ER patients, and
      arrestees.
AB  - This paper examines the validity of self-report of drug use in several important
      high-risk samples by comparing survey answers with urinalysis results. The
      analyses include data obtained from face-to-face interviews with 1536 patients in
      sexually transmitted disease (STD) clinics, 1564 patients in hospital emergency
      rooms (ERs), and 2034 recent arrestees in jails. Using urinalysis as the
      criterion measure, considerable underreporting was observed, particularly among
      STD and ER subjects using cocaine and opiates. A logistic regression analysis on
      factors related to the underreporting was conducted for both cocaine and opiates.
      The results showed that a lower degree of underreporting was associated with
      subjects at jail sites (compared to STD subjects) and those who self-reported
      lifetime drug dependence.

PMID- 10078980
TI  - After drug treatment: are 12-step programs effective in maintaining abstinence?
AB  - Although participation in 12-step programs is now widely utilized as a treatment
      aftercare resource by individuals with drug and alcohol problems, little is known
      about the effectiveness of such a practice. This paper identifies gaps in the
      existing literature and articulates methodological concerns that may compromise
      investigations of 12-step programs. It highlights the need for additional after
      treatment studies, and it presents findings from a 24-month longitudinal after
      treatment study that suggests the effectiveness of 12-step programs. Rather than
      a behavioral indicator of recovery motivation or a spurious relationship
      confounded by additional treatment, aftercare, or alumni activities that occur
      simultaneously with 12-step participation, the findings suggest that weekly or
      more frequent 12-step participation is associated with drug and alcohol
      abstinence. Less-than-weekly participation is not associated with favorable drug
      and alcohol use outcomes, and participation in 12-step programs seems to be
      equally useful in maintaining abstinence from both illicit drug and alcohol use.
      These findings point to the wisdom of a general policy that recommends weekly or
      more frequent participation in a 12-step program as a useful and inexpensive
      aftercare resource for many clients.

PMID- 10078981
TI  - Depressive symptoms, drug network, and their synergistic effect on needle-sharing
      behavior among street injection drug users.
AB  - In this study, we examined the relationship between depressive symptoms and
      needle-sharing behavior in a community sample of intravenous drug users (N = 499)
      in Baltimore, Maryland. Based on the polytomous logistic regression, higher
      depressive symptoms were positively associated both with needle sharing after
      cleaning with bleach and with needle sharing without first cleaning with bleach
      at the bivariate analyses. This relationship remained significant (OR = 1.66)
      even after adjusting for demographic characteristics, life events, drug use
      patterns, and social and drug networks. A significant synergistic effect of
      depressive symptoms and drug network on needle sharing after cleaning with bleach
      and needle sharing without cleaning was observed. More depressed intravenous drug
      users who also had a larger drug network were found to be at higher risk of
      needle sharing after cleaning with bleach, as well as needle sharing without
      cleaning (OR = 2.59). Depression status is discussed as a predisposing factor and
      drug network size as a precipitating factor for needle-sharing behavior.
      Implications for preventing needle-sharing behavior by reducing depressive
      symptoms are discussed.

PMID- 10078982
TI  - Women inmates' risky sex and drug behaviors: are they related?
AB  - The large concentration of female illicit drug users in state correctional
      facilities prompted an examination of the associations among different types of
      drug use and sexual risk factors related to human immunodeficiency virus (HIV)
      among women inmates. A consecutive sample of 805 women felons admitted to the
      North Carolina Correctional Institution for Women between July 1991 and November
      1992 was interviewed. Of these inmates, 651 had complete information on relevant
      characteristics. Of the women inmates, 73% had used drugs prior to incarceration;
      most women were crack smokers only (33%), followed by non-drug users (27%), other
      drug users (19%), crack-smoking injecting drug users (15%), and injecting drug
      users only (6%). Inconsistent condom use with multiple sex partners, a history of
      a diagnosed sexually transmitted disease (STD), a drug-injecting sex partner, or
      exchanging sex for money or drugs prior to incarceration were reported by 55% of
      the women. Sexual risk factors differed across different types of drug users,
      with crack-smoking injectors being placed at greatest potential risk for exposure
      to heterosexually transmitted HIV, followed by injecting drug users, crack
      smokers, and then other drug users. Given the differential associations between
      sexual risk factors and types of drug use, prison-based sexual-risk reduction
      strategies should be tailored to specific types of drug users. In times of
      limited resources, special attention should be given to crack smokers and/or drug
      injectors.

PMID- 10078983
TI  - Using measures of readiness to change in individuals with schizophrenia.
AB  - The literature suggests that substance abuse treatment for schizophrenia patients
      should consider both the patients' readiness for active treatment and matching
      phases of intervention with phases of the patient's acceptance of his or her dual
      problems. This study assessed the suitability of existing measures of "readiness
      to change" for use with individuals with schizophrenia. Outpatients (n = 39) with
      a diagnosis of schizophrenia and alcohol and/or drug dependency or abuse were
      given three measures to assess the stage of readiness to change. Results
      suggested that there was no agreement between stages defined by the interviewer
      and stages defined by self-report. This has implications for assessing readiness
      to change in terms of substance use in a population with schizophrenia.

PMID- 10078984
TI  - University students' perceptions of tobacco, cocaine, and homicide fatalities.
AB  - A questionnaire was given to 350 students in introductory-level and 46 students
      in senior-level university courses to determine how accurately students are able
      to estimate the annual number of deaths in the United States from tobacco use,
      cocaine use, and homicide. Results show that students dramatically overestimate
      the number of cocaine-related deaths and homicides, but dramatically
      underestimate the number of tobacco-related deaths. The data indicate that
      students generally have a poor grasp in both absolute and relative terms of the
      dangers inherent in tobacco use. Results are attributed to the mixed message
      young people receive about tobacco, with tobacco ads countering the effects of
      government health warnings, in contrast to the media's consistent emphasis on the
      dangers of illegal drugs and crime.

PMID- 10078985
TI  - Symptomatology of depression and anxiety in female "social drinkers".
AB  - Self-reported alcohol use, Beck Depression Inventory (BDI), and Beck Anxiety
      Inventory (BAI) scores were obtained during on-site interviews of 172 female
      applicants for paid participation in behavioral research. Mood symptomatology as
      reflected in BDI and BAI scores was analyzed as a function of alcohol use and
      other demographic variables. Women reporting even light alcohol use (up to three
      drinks per week) were significantly more symptomatic than abstinent women. In
      contrast, no significant differences in symptomatology were observed due to race
      or education level. This analysis extends previous findings of depressed mood in
      women (while sober) whose lifestyle includes moderate alcohol consumption and
      suggests that even light alcohol use is related to depressed and/or anxious mood.

PMID- 10078986
TI  - SK&F 83959 and non-cyclase-coupled dopamine D1-like receptors in jaw movements
      via dopamine D1-like/D2-like receptor synergism.
AB  - This study compared the effects of the dopamine D1-like receptor agents SK&F
      83959 (3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro- 1
      H-3-benzazepine), which inhibits the stimulation of adenylyl cyclase, and A 68930
      ([1R,3S]-1-aminomethyl-5,6-dihydroxy-3-phenyl-isochroman), a full efficacy
      agonist, in regulating jaw movements in the rat by synergism with dopamine D2
      like receptor agonism. When SK&F 83959 and A 68930 were given in combination with
      quinpirole, there was a synergistic induction of jaw movements. Responsivity to
      SK&F 83959 + quinpirole was antagonised by the dopamine D1-like receptor
      antagonists SCH 23390 ([R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5
      tetrahydro-1H-3-ben zaz epine) and BW 737C ([S]-6-chloro-1-[2,5-dimethoxy-4
      propylbenzyl]-7-hydroxy-2-methyl- 1,2,3,4-tetrahydroisoquinoline); synergism was
      antagonised also by the dopamine D2-like receptor antagonist YM 09151-2 (cis-N-[1
      benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-++ +methyl-aminobenzamide).
      Responsivity to A 68930 + quinpirole was enhanced by low doses of SCH 23390, BW
      737C and YM 09151-2, and antagonised by higher doses of SCH 23390 and YM 09151-2.
      These results implicate a novel, dopamine D1-like receptor that is coupled to a
      transduction system other than/additional to adenylyl cyclase, and suggest that
      its functional role extends to the regulation of jaw movements by synergistic
      interactions with dopamine D2-like receptors.

PMID- 10078987
TI  - Effects of nocistatin on nociceptin-induced impairment of learning and memory in
      mice.
AB  - We investigated the effects of nociceptin/orphanin FQ and nocistatin on learning
      and memory function as measured in a step-down type passive avoidance task and
      spontaneous alternation of Y-maze with mice. Nociceptin (0.5-5.0 nmol/mouse,
      i.c.v.) 30 min before the training session or Y-maze test, dose dependently
      shortened the step-down latency and impaired spontaneous alternation, while there
      was no significant effect of nocistatin (0.5-5.0 nmol/mouse). Interestingly,
      nocistatin (5.0 nmol) significantly improved the nociceptin (5.0 nmol)-induced
      impairment of learning and memory without changing motor activity or response to
      electric shocks. These results suggest that nocistatin, a new biologically active
      peptide now found to also counteract the impairment of learning and memory
      induced by nociceptin, plays an important role in the regulation of learning and
      memory process in the central nervous system.

PMID- 10078988
TI  - Chronic administration of adenosine A3 receptor agonist and cerebral ischemia:
      neuronal and glial effects.
AB  - We have previously shown that chronic administration of the selective A3 receptor
      agonist N6-(3-iodobenzyl)-5'-N-methylcarboxoamidoadenosine (IB-MECA) leads to a
      significant improvement of postocclusive cerebral blood flow, and protects
      against neuronal damage and mortality induced by severe forebrain ischemia in
      gerbils. Using immunocytochemical methods we now show that chronic with IB-MECA
      results in a significant preservation of ischemia-sensitive microtubule
      associated protein 2 (MAP-2), enhancement of the expression of glial fibrillary
      acidic protein (GFAP), and a very intense depression of nitric oxide synthase in
      the brain of postischemic gerbils. These changes demonstrate that the
      cerebroprotective actions of chronically administered IB-MECA involve both
      neurons and glial cells, and indicate the possibility of distinct mechanisms that
      are affected in the course of chronic administration of the drug.

PMID- 10078989
TI  - Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid
      decarboxylase in mouse brain.
AB  - We have previously demonstrated that bilobalide, a constituent of the Ginkgo
      biloba extract, possesses anticonvulsant activity, and suggested that the
      mechanism of its anticonvulsant action involves modulation of y-aminobutyric acid
      (GABA)-related neuronal transmission. This study examined the effects of
      bilobalide on the level of GABA and glutamate, the activity and the amount of
      glutamic acid decarboxylase (EC 4.1.1.15), and the function of GABA(A) receptors
      in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels,
      glutamic acid decarboxylase activity, and the protein amount of 67 kDa glutamic
      acid decarboxylase in the hippocampus of mice treated with bilobalide (30 mg/kg,
      p.o., once a day for 4 days) were significantly higher than those in controls.
      However, there were no significant differences in glutamate levels or, the number
      and the dissociation constants of GABA(A) receptors in the hippocampus between
      control and bilobalide-treated mice. These results suggest that the
      anticonvulsant effect of bilobalide is due to elevation of GABA levels, possibly
      through potentiation of glutamic acid decarboxylase activity and enhancement of
      the protein amount of 67 kDa glutamic acid decarboxylase by bilobalide.

PMID- 10078990
TI  - Comparison between dopamine transporter affinity and self-administration potency
      of local anesthetics in rhesus monkeys.
AB  - Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in
      rodent brain. Additionally, local anesthetics are self-administered in rhesus
      monkeys. The present study determined binding affinities of cocaine and five
      local anesthetics at dopamine transporters in rhesus monkey brain, and compared
      binding affinities to published self-administration potencies in rhesus monkeys.
      The affinity order at dopamine transporters was cocaine > dimethocaine >
      tetracaine > procaine > or = chloroprocaine > lidocaine. The correlation between
      dopamine transporter affinities and self-administration potencies was
      significant. Binding affinities were also determined at sodium (Na2+) channels in
      rhesus monkey brain. There was not a significant correlation between Na2+ channel
      affinities and self-administration potencies Local anesthetics with high dopamine
      transporter and low Na2+ channel affinities were self-administered, whereas those
      with either high or low affinity at both sites were not consistently self
      administered. These data suggest that affinity at dopamine transporters is
      related to the reinforcing effects of local anesthetics in rhesus monkeys, and
      Na2+ channel effects may interfere with the reinforcing effect of these drugs.

PMID- 10078991
TI  - Selective agonists of metabotropic glutamate receptors elicit significant EEG
      effects when infused in the nucleus accumbens of rats.
AB  - The effect of intra-accumbens infusion of selective group I ((S)-3,5
      dihydroxyphenylglycine, DHPG), group II ((2S,3S,4S)-CCG/(2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine, L-CCG-I) and group III ((L-(+)-2-amino-4
      phosphonobutyric acid, L-AP4) metabotropic glutamate (mGlu) receptor agonists was
      studied in male Wistar rats. A computerised electroencephalographic (EEG) power
      spectral analysis was performed. While DHPG (400 nmoles) induced EEG and
      behavioural limbic seizures, L-CCG-I (400 nmoles) and L-AP4 (800 nmoles) induced
      a 'depressant' EEG with an increase in relative power in the slow-frequency bands
      and a decrease in relative power in the high-frequency bands) and behavioural
      effects. These results show for the first time that the stimulation of groups I,
      II and III mGlu receptors located in the nucleus accumbens significantly
      influences the EEG tracing in rats.

PMID- 10078992
TI  - Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic
      pain in rats.
AB  - We studied spinal analgesic and antiallodynic effects of endomorphin-1 and
      endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly-ol
      (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats
      chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2
      (2.5, 5, 10 microg i.t.) increased the tail-flick latency and, to the lesser
      extent, the paw pressure latency. The range of potencies in both those models of
      acute pain was as follows: DAMGO > morphine = endomorphin-1 > endomorphin-2. In a
      model of inflammatory pain, the number of formalin-induced flinching episodes was
      decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced.
      Both DAMGO and morphine significantly inhibited the pain-related behavior evoked
      by formalin. In a neuropathic pain model (sciatic nerve crushing in rats),
      endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on
      the tail-flick latency and on the cold-water tail flick latency. Morphine, 5
      microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.)
      dose-dependently antagonized allodynia. Those effects of endomorphins were
      antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain
      models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In
      conclusion, our results show a strong analgesic action of endomorphins at the
      spinal cord level. The most interesting finding is a strong, stronger than in the
      case of morphine, antiallodynic effect of endomorphins in rats subjected to
      sciatic nerve crushing, which suggests a possible use of these compounds in a
      very difficult therapy of neuropathic pain.

PMID- 10078993
TI  - 5-HT2A receptor or alpha1-adrenoceptor activation induces excitatory postsynaptic
      currents in layer V pyramidal cells of the medial prefrontal cortex.
AB  - We compared 5-hydroxytryptamine (5-HT), norepinephrine and dopamine for their
      efficacy at increasing excitatory postsynaptic current frequency in layer V
      pyramidal cells from rat medial prefrontal cortical slices. 5-HT, norepinephrine
      and dopamine increased the excitatory postsynaptic current frequency by 15.9-,
      4.5- and 1.7-fold, respectively. Similar to previous results with 5-HT-induced
      excitatory postsynaptic currents, blockade of mu-opioid receptors, of alpha-amino
      3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors and fast Na+
      channels suppressed the norepinephrine-induced excitatory postsynaptic currents.
      The norepinephrine-induced, and in most cases, the dopamine-induced increase in
      excitatory postsynaptic current frequency was blocked by the alpha1-adrenoceptor
      antagonist prazosin while the alpha2-adrenoceptor antagonist yohimbine did not
      block either the norepinephrine- or the 5-HT-induced increase in excitatory
      postsynaptic currents frequency. The potency of three 5-HT2 receptor antagonists
      with varying selectivity for 5-HT2A/2B/2C receptors tested against the 5-HT
      induced increase in excitatory postsynaptic current frequency are in agreement
      with the affinity of these drugs for the 5-HT2A receptor. These findings suggest
      that 5-HT2A receptor or alpha1-adrenoceptor activation enhance neurotransmitter
      release from a similar subset of glutamate terminals that innervate apical
      dendrites of layer V pyramidal cells.

PMID- 10078994
TI  - Evaluation of 3-aminopropanesulphonamide analogues of GABA as antagonists at
      GABA(B) receptors in peripheral and central preparations.
AB  - Cholinergic twitch responses in the guinea-pig isolated ileum, and spontaneous
      discharges in rat neocortical slices, were depressed by the GABA(B) receptor
      agonist baclofen. These actions were reversibly antagonised by the sulphonamide
      derivatives (R,S)-2-hydroxy-3-phthalimidopropanesulphonamide (HPIPS), 3-amino-N
      benzoylpropanesulphonamide (ABPS) and 3-phthalimidopropanesulphonamide (PIPS)
      which produced rightwards shifts of the baclofen concentration-response curves,
      with pA2 values ranging between 4.1 and 4.3 in both preparations. From these
      results, HPIPS, ABPS and PIPS constitute a novel class of antagonists at GABA(B)
      hetero-receptors.

PMID- 10078995
TI  - Relationship among cholesterol, superoxide anion and endothelium-dependent
      relaxation in diabetic rats.
AB  - The purpose of the present study was to investigate the time course of changes in
      plasma low-density lipoprotein (LDL) cholesterol, tissue lipid peroxidation, the
      expression of hepatic LDL-receptor mRNA and aortic superoxide dismutase, and the
      relaxation response to acetylcholine in streptozotocin-induced diabetic rats.
      Plasma cholesterol and LDL levels were significantly increased in both 4- and 10
      week diabetic rats. The tissue malonic dialdehyde content in aortas was increased
      in 10-week compared to 1- or 4-week diabetic rats. The expression of mRNA for LDL
      receptor mRNA in the liver showed a decrease in both 4- and 10-week diabetic
      rats. Hepatic LDL-receptor binding activity decreased significantly in 10-week
      diabetic rats, and decreased binding activity in diabetic rats was improved by
      the chronic administration of cholestyramine. The relaxation responses to
      acetylcholine in helical strips of the aorta precontracted with noradrenaline
      were significantly decreased in 10-week, but not in 1- or 4-week streptozotocin
      induced diabetic rats. The decreased relaxation response to acetylcholine was
      improved by chronic cholestyramine. Both the expression of Mn-superoxide
      dismutase mRNA and the activity of superoxide dismutase in the aorta were
      decreased in 10-week, but not in 4-week diabetic rats. From time-course studies,
      our data suggest that not only increased LDL cholesterol but also decreased
      activity of superoxide dismutase are responsible for the decreased relaxation
      response induced by acetylcholine.

PMID- 10078996
TI  - Endothelial nitric oxide release in isolated perfused ovine uterine arteries:
      effect of pregnancy.
AB  - The present study was designed to determine the release of endothelial nitric
      oxide, measured as combined nitric oxide, nitrite and nitrate (NOx), in isolated
      perfused uterine arteries obtained from nonpregnant and pregnant sheep.
      Noradrenaline produced concentration-dependent increases in perfusion pressure in
      both nonpregnant and pregnant uterine arteries with pD2 values of 5.1+/-0.07 and
      4.6+/-0.04, respectively. The maximum responses were 300.8+/-8.8 mmHg for
      nonpregnant arteries and 86.9+/-1.3 mmHg for pregnant ones. N(G)-nitro-L-arginine
      increased noradrenaline-mediated maximum response in the pregnant (86.9+/-1.3 to
      144.6+/-5.1 mmHg), but not in the nonpregnant, uterine arteries. The basal level
      of NOx was significantly higher in pregnant than in nonpregnant uterine arteries
      (346.1+/-63.2 vs. 86.0+/-20.6 pmol/ml). The calcium ionophore A23187 and
      adenosine triphosphate produced concentration-dependent increases in NOx release
      in both nonpregnant and pregnant arteries. Compared to the nonpregnant tissue,
      the agonist-induced increase in NOx release was significantly enhanced in the
      pregnant uterine artery. In accordance, endothelial NO synthase protein
      expression in pregnant uterine artery was 197% of that in nonpregnant artery.
      These data indicate that in the uterine artery, pregnancy increases both basal
      and agonist-induced release of endothelial nitric oxide, which is likely to play
      a key role in attenuated vascular reactivity of the uterine artery to
      vasoconstrictors during the course of pregnancy.

PMID- 10078997
TI  - Contribution of nitric oxide and K+ channel activation to vasorelaxation of
      isolated rat aorta induced by procaine.
AB  - The endothelium-dependent and -independent relaxant effect of procaine was
      examined in isolated rat aortic rings. Procaine induced relaxation of arteries
      precontracted with phenylephrine or with 60 mM K+ in a concentration-dependent
      manner (0.01-3 mM). Procaine (1 mM) inhibited the transient contraction induced
      by caffeine (10 mM) in Ca2+-free Krebs solution. Removal of the endothelium
      caused a rightward shift of the concentration-response curve for procaine. N(G)
      Nitro-L-arginine (L-NNA, 10-100 microM), N(G)-nitro-L-arginine methyl ester (L
      NAME, 100 microM) and methylene blue (1-10 microM) significantly attenuated the
      procaine-induced relaxation without affecting the maximal response. L-Arginine (1
      mM) partially but significantly antagonized the effect of L-NAME (100 microM).
      Pretreatment of endothelium-intact aortic rings with procaine (1 mM) or with
      acetylcholine (10 microM) significantly elevated the tissue contents of cyclic
      GMP and this increase was inhibited in the presence of 100 microM L-NNA.
      Tetrapentylammonium ions (1-3 microM) reduced the procaine-induced relaxation in
      both endothelium-intact and -denuded arteries. Tetrapentylammonium ions (3
      microM) did not affect the procaine-induced relaxation of 60 mM K+-contracted
      arteries. Tetraethylammonium ions (3 mM) inhibited the procaine-induced
      relaxation. In contrast, iberiotoxin (100 nM), glibenclamide (3 microM), 4
      aminopyridine (3 mM) and indomethacin (10 microM) had no effect. These results
      indicate that the procaine-induced relaxation may be mediated through multiple
      mechanisms. A substantial portion of the procaine-induced relaxation in rat aorta
      was caused by nitric oxide but not by other endothelium-derived factors. The
      activation of tetrapentylammonium- and tetraethylammonium-sensitive K+ channels
      contributes in part to the procaine-induced vasorelaxation. Besides, procaine may
      directly inhibit both external Ca2+ entry and internal Ca2+ release in aortic
      smooth muscle cells.

PMID- 10078998
TI  - Endogenous calcitonin gene-related peptide suppresses vasoconstriction mediated
      by adrenergic nerves in rat mesenteric resistance blood vessels.
AB  - The role of perivascular calcitonin gene-related peptide (CGRP)-containing nerves
      in the modulation of adrenergic nerve-mediated vasoconstrictions was studied in
      the rat perfused mesenteric vascular bed. A frequency-dependent vasoconstriction
      induced by periarterial nerve stimulation (1-6 Hz) of the bed was significantly
      potentiated by perfusion of 1 microM CGRP-(8-37) (CGRP receptor antagonist) or to
      a similar extent after treatment with 500 nM capsaicin. In the preparations
      treated with capsaicin, CGRP-(8-37) caused a small potentiation of periarterial
      nerve stimulation-induced vasoconstriction. Exogenous CGRP (0.1-1 nM)
      concentration-dependently attenuated the augmented vasoconstriction in response
      to periarterial nerve stimulation after treatment with capsaicin. However,
      exogenous CGRP (1 nM) did not attenuate the periarterial nerve stimulation
      induced vasoconstriction in the bed untreated with capsaicin. These results
      suggest that endogenous CGRP, which is released from CGRP-containing nerves,
      suppresses the adrenergic nerve function involved in mechanisms regulating the
      tone of resistant blood vessels.

PMID- 10078999
TI  - Relaxant effect of 2-methyl-thio-adenosine diphosphate on rat thoracic aorta:
      effect of clopidogrel.
AB  - The main aim of this study was to determine the functional effect of 2-methyl
      thio-adenosine diphosphate (2MeS-ADP) on vascular purinoceptors, in comparison
      with that of a characterised agonist of the P2Y1 receptor, 2-methyl-thio
      adenosine triphosphate (2MeS-ATP), and of the P2Y2 receptor, uridine triphosphate
      (UTP). On phenylephrine-precontracted rat aortic rings, mounted isometrically in
      organ baths, we found that 2MeS-ADP (10(-9) to 10(-6) M) induced concentration
      dependent relaxation of rings with a functional endothelium. Mechanical removal
      of the endothelium abolished the relaxant effect of 2MeS-ADP. The 2MeS-ADP
      induced relaxation of phenylephrine-precontracted rings was inhibited by Nomega
      nitro-L-arginine methyl ester (L-NAME) (100 microM) but not by indomethacin (100
      microM) or aspirin (1 mM), indicating that the 2MeS-ADP-induced relaxation was
      nitric oxide (NO) synthase-mediated but not cyclooxygenase-dependent. Repeated
      stimulation with 2MeS-ADP resulted in desensitisation of the receptor. Under
      these conditions, the relaxant effect of 2MeS-ATP was abolished. On the contrary,
      UTP-induced relaxation was not affected, showing that 2MeS-ADP and 2MeS-ATP but
      not UTP shared the same receptor. Suramin (100 microM), a non-specific P2
      inhibitor, abolished the effect of 2MeS-ADP, 2MeS-ATP and UTP. In contrast,
      pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) and adenosine-3'
      phosphate-5'-phosphosulphate (A3P5PS) abolished only the vasodilator responses to
      2MeS-ADP and 2MeS-ATP and did not affect the relaxant effect of UTP, showing that
      2MeS-ADP acted through the P2Y1 receptor. Clopidogrel, a potent platelet ADP
      receptor antagonist, at a dose that strongly inhibited ADP-induced platelet
      aggregation ex vivo, did not modify the relaxant responses to 2MeS-ADP or 2MeS
      ATP. In conclusion, these results showed that 2MeS-ADP induces endothelium
      dependent, NO-mediated relaxation of rat aortic rings. This effect, resistant to
      clopidogrel treatment, occurred through activation of the P2Y1 receptor.

PMID- 10079000
TI  - Effects of systemic treatment with irbesartan and losartan on central responses
      to angiotensin II in conscious, normotensive rats.
AB  - Angiotensin AT1 receptor antagonists represent a novel class of cardiovascular
      drugs. In conscious, normotensive rats, irbesartan ((2-n-butyl-3-[(2'-(1H
      tetrazol-5-yl)-biphenyl-4-yl) methyl]-1,3-diaza-spiro[4,4]non) and losartan ((2 n
      butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl -4-yl) methyl]
      imidazol), two specific, high- affinity angiotensin AT1 receptor antagonists
      administered intravenously (i.v.) at doses of 0.3, 1, 3 and 10 mg/kg body weight,
      or orally (p.o.) at doses of 1, 3, 10 and 30 mg/kg body weight, antagonized the
      pressor responses to i.v. angiotensin II (50 ng/kg body weight) in a dose-related
      manner and with similar potency. In the following sets of experiments, we tested
      the hypothesis that these angiotensin AT1 receptor antagonists, when applied
      systemically, can inhibit the effects of angiotensin AT1 receptor stimulation in
      the brain. Irbesartan and losartan were administered i.v. or p.o. at doses of 3,
      10, 30 and 100 mg/kg body weight. The responses to 100 ng angiotensin II injected
      into the lateral brain ventricle (i.c.v.), namely blood pressure increase,
      vasopressin release into the circulation and drinking, were recorded for up to 3
      h. While both angiotensin AT1 receptor antagonists dose-dependently attenuated
      the pressor responses to central angiotensin AT1 receptor stimulation to a
      similar degree (maximal inhibition, irbesartan: 62% i.v., 39% p.o.; losartan: 62%
      i.v., 46% p.o.; respectively), irbesartan was more effective with respect to the
      inhibition of vasopressin release (76% i.v., 65% p.o.) and drinking (63% i.v.,
      79% p.o.) than losartan (58% i.v., 33% p.o and 22% i.v., 56% p.o., respectively).
      We conclude that systemically administered angiotensin AT1 receptor antagonists
      have access to central angiotensin receptors. The degree of central angiotensin
      AT1 receptor blockade following peripheral application may vary between different
      representatives of this class of drugs.

PMID- 10079001
TI  - The anti-ischemic effects of CP-060S during pacing-induced ischemia in
      anesthetized dogs.
AB  - CP-060 S, (-)-( S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl
      N-[2-(3 ,4-methylenedioxyphenoxy)ethyl]-amino]propyl]-1,3-thiazolidin++ +-4-one
      hydrogen fumarate, is a novel cardioprotective drug which prevents Na+-, Ca2+
      overload and has Ca2+ channel blocking activity. We compared the anti-ischemic
      effects of CP-060S with those of diltiazem, a Ca2+ channel blocker, and R56865, N
      [1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine, a Na+
      , Ca2+-overload inhibitor, in a canine pacing-induced ischemia model. CP-060S 100
      microg kg(-1) significantly suppressed the pacing-induced ischemic epicardial ST
      segment elevation by maximally 75%, while diltiazem 100 microg kg(-1) suppressed
      it by maximally 35%. R56865 100 microg kg(-1) significantly suppressed the ST
      segment elevation by maximally 30%. In addition, diltiazem 100 microg kg(-1)
      caused synergistic suppression of ST-segment elevation by 70% when administered
      simultaneously with R56865 100 microg kg(-1). These results suggest that a Na+-,
      Ca2+-overload preventive action and a Ca2+ channel blocking action independently
      contribute to the suppression of the ST-segment elevation. Therefore, CP-060S may
      suppress pacing-induced ST-segment elevation by a dual action by preventing Na+-,
      Ca2+-overload and the Ca2+ channel blockade.

PMID- 10079002
TI  - Antiaggregatory, antithrombotic effects of MS-180, a novel platelet glycoprotein
      IIb/IIIa receptor antagonist.
AB  - The antiaggregatory and antithrombotic effects of (S)-(-)-ethyl[6-[4
      (morpholinoformimidoyl)benzamido]-3,4-dihydro-2 H-1-benzo-pyran-3-yl]acetate
      hydrochloride (MS-180), a novel platelet glycoprotein IIb/IIIa receptor
      antagonist, were investigated. Ma-HCl, (S)-(-)-[6-[4
      (Morpholinoformimidoyl)benzamido]-3,4-dihydro-2H-1-b enzopyran-3-yl]acetic acid
      hydrochloride, the hydrochloride salt of Ma (active metabolite), inhibited the
      binding of fibrinogen to immobilized human glycoprotein IIb/III receptor with an
      IC50 value of 0.12+/-0.03 nM without affecting binding to either fibronectin or
      vitronectin receptors. In anesthetized guinea pigs, intraduodenal administration
      of MS-180 caused dose-dependent inhibition of both ADP- and collagen-induced ex
      vivo platelet aggregation. At the same dosages, occluded thrombus formation and
      platelet release reactions were also markedly suppressed. In anesthetized dogs,
      the bleeding time was prolonged slightly even when submaximal inhibition (< 90%)
      of ex vivo platelet aggregation was achieved following i.v. administration of Ma
      HCl. Aspirin (100 mg/kg) prolonged the bleeding time to the same extent as MS-180
      (1 mg/kg), although it suppressed only collagen-induced platelet aggregation.
      Therefore, MS-180 may be clinically useful for the treatment of thrombotic
      diseases.

PMID- 10079003
TI  - Characterisation of the contractile activity of eletriptan at the canine vascular
      5-HT1B receptor.
AB  - The functional activity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2
      (phenylsulphonyl )ethyl]- 1 H-indole) at the contractile serotonin (5
      hydroxytryptamine; 5-HT) '1B-like' receptor in dog isolated saphenous vein and
      basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently
      contracted saphenous vein (pEC50: 6.3, 6.9 and 6.1, respectively) and basilar
      artery (pEC50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by
      eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT
      (intrinsic activity saphenous vein: eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85;
      basilar artery: eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions
      evoked by eletriptan were antagonised by the 5-HT1B/1D receptor antagonist
      GR125743 (N-[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4
      pyridyl)benzamide) with pA2 values of 9.1 in saphenous vein and 9.4 in basilar
      artery. Affinity estimates (pKA) for 5-HT and sumatriptan determined from
      receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively,
      compared to the apparent equilibrium dissociation constant (pKp) for eletriptan
      of 6.8. The rank order of relative intrinsic efficacies (epsilon) was 5-HT >
      sumatriptan > eletriptan. Thus, eletriptan required greater receptor occupancy
      (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog
      isolated saphenous vein. These data demonstrate that eletriptan is a potent
      partial agonist at the canine vascular 5-HT1B receptor.

PMID- 10079004
TI  - Functional characterization of alpha1-adrenoceptor subtypes in longitudinal and
      circular muscle of human vas deferens.
AB  - The alpha1-adrenoceptor subtype(s) mediating contraction to noradrenaline in
      longitudinal and circular muscle of human epididymal vas deferens was studied
      using competitive antagonists. The effects of the alkylating agents,
      phenoxybenzamine and chloroethylclonidine were also investigated. Noradrenaline
      evoked concentration-dependent contractions of longitudinal and circular muscle
      with comparable potencies (pD2; 5.6 and 5.5 respectively). The contractions in
      longitudinal and circular muscle respectively were inhibited by prazosin (pA2,
      8.6 and pKB, 9.2), 5-methylurapidil (pKB, 8.7 and 9.1) and less potently by
      spiperone (pA2, 7.1) or BMY 7378 (pKB, 6.3 and 6.6). Contractions of the circular
      but not longitudinal muscle was comparatively insensitive to pretreatment with
      phenoxybenzamine. In contrast pretreatment with chloroethylclonidine reduced the
      contractions in both muscle types and also enhanced phenoxybenzamine-sensitivity
      in longitudinal but not circular muscle. The results suggest that contractions
      evoked by noradrenaline in both muscle types of human vas deferens is mediated
      via activation of alpha1-adrenoceptors with pharmacological profile of the
      alpha1A-subtype. However the involvement of alpha1A-adrenoceptor variants, such
      as the hypothesised alpha1L-subtype may underlie the differential effects of
      phenoxybenzamine in longitudinal and circular muscle. Factors contributing to
      chloroethylclonidine-sensitivity are discussed.

PMID- 10079005
TI  - Effects of halothane on renal hemodynamics and interstitial nitric oxide in
      rabbits.
AB  - The effects of halothane on renal hemodynamics and the nitric oxide (NO)
      guanylate cyclase signaling pathway were examined in anesthetized rabbits using a
      renal microdialysis method. Halothane (0.5 and 2 vol%) caused dose-dependent
      decreases in blood pressure, renal blood flow and the renal interstitial
      concentrations of guanosine 3',5'-cyclic monophosphate (cGMP) or nitrate
      (NO2)/nitrite (NO3). Sodium nitroprusside (20 microg kg(-1) min(-1), i.v.) under
      the inhalation of halothane (2 vol%) increased the renal interstitial
      concentration of cGMP. L-Arginine (priming dose, 300 mg kg(-1) 10 min(-1);
      sustaining dose, 50 mg kg(-1) min(-1), i.v.) did not reverse halothane-induced
      reductions of cGMP and NO2/NO3. These findings demonstrate that halothane caused
      a renal vasoconstriction and inhibited the NO-guanylate cyclase signaling pathway
      in the kidney. Moreover, it is possible that the renal hemodynamic responses to
      halothane might have been induced, in part, through this inhibition. Finally, it
      can be assumed that halothane did not interfere with the activation process of
      guanylate cyclase by NO.

PMID- 10079006
TI  - Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in
      proximal rat trachea.
AB  - The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase
      activity in the proximal rat trachea. Sodium nitroprusside induced concentration
      dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase
      activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was
      unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity
      in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium
      nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP
      levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by
      sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM)
      and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic
      GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were
      blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor),
      but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase
      inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity,
      but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1
      inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The
      effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+
      ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+,
      K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.

PMID- 10079007
TI  - Effect of deramciclane, a new 5-HT receptor antagonist, on cholecystokinin
      induced changes in rat gastrointestinal function.
AB  - Recent studies suggested that serotonin receptors may be involved in modulating
      the actions of cholecystokinin (CCK) in the gastrointestinal tract. The present
      work was designed to compare the effects of deramciclane, a recently developed
      serotonin-2 (5-HT2A/2C) receptor antagonist, and lorglumide, a CCK(A) receptor
      antagonist, on exogenous and endogenous CCK-induced pancreatic enzyme secretion
      and pancreatic growth, as well as on the emptying of the stomach and the
      gallbladder. Pancreatic secretory function was tested while CCK release was
      evoked by diversion of bile-pancreatic juice in rats. Adaptive growth of the
      pancreas was induced by chronic intragastric administration of camostate, a
      potent synthetic trypsin inhibitor in rats. Gastric emptying of a noncaloric test
      meal was investigated in response to intraduodenal intralipid infusion, also in
      rats. In fasted mice, gallbladder emptying was examined in response to
      intragastric egg yolk administration. In rats, diversion of bile-pancreatic juice
      from the duodenum stimulated pancreatic amylase secretion. This action was
      blocked by deramciclane and by lorglumide. Pancreatic hypertrophy and hyperplasia
      induced by chronic camostate administration was also suppressed by both the
      serotonin- and the CCK-receptor antagonists. Intraduodenal administration of
      intralipid induced a significant delay in gastric emptying. This effect was
      inhibited by both deramciclane and lorglumide in rats. In mice, intragastric
      administration of egg yolk elicited an accelerated release of bile from the
      gallbladder. Prior treatment with either deramciclane or lorglumide abolished
      this response. Lorglumide was able to inhibit the functional responses elicited
      by exogenous CCK administration in both pancreas, stomach and gallbladder, while
      deramciclane was not effective under such circumstances. Our data show that
      deramciclane inhibited the effects of CCK on pancreatic, gastric and gallbladder
      function when its endogenous release was stimulated, but did not alter the
      effects of exogenously administered peptide. These results suggest that
      serotonin, primarily via 5-HT2A receptors, may modulate CCK-mediated
      gastrointestinal functions in rats.

PMID- 10079008
TI  - Characterization of the muscarinic receptor subtype that mediates the contractile
      response of acetylcholine in the swine myometrium.
AB  - The aim of the present study was to characterize the subtype of muscarinic
      receptor that mediates acetylcholine-induced contractions in the nonpregnant
      proestrus swine myometrium by means of mechanical, radioligand ([3H]quinuclidinyl
      benzilate) binding and biochemical (measurement of cyclic AMP) approaches.
      Acetylcholine (-logEC50, 6.12), oxotremorine-methiodide (6.47), methacholine
      (6.35), carbachol (6.18) and muscarine (6.33) caused contractile responses of the
      uterine circular muscle, with a similar maximum amplitude, but pilocarpine and
      McN-A-343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium) were
      ineffective in causing contraction. The contractile response to acetylcholine was
      antagonized by the following muscarinic receptor antagonists in a competitive
      manner (with pA2 values in parentheses): atropine (8.95), 4-diphenylacetoxy-N
      methylpiperidine (4-DAMP, 8.83), tropicamide (7.07), himbacine (7.01),
      pirenzepine (6.42) and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11
      dihydro-6H-pyri do[2,3 b][1,4]benzodiazepin-6-one (AF-DX116, 5.96). Electrical
      field stimulation (10 Hz) caused tetrodotoxin- and atropine-sensitive
      contractions in the circular muscle. All muscarinic receptor antagonists
      decreased the electrical field stimulation-induced contraction in a concentration
      dependent manner. The order of inhibition (-logIC50) was 4-DAMP (8.35) >
      tropicamide (6.72) > himbacine (6.54) > pirenzepine (6.31)> AF-DX116 (6.13).
      Acetylcholine did not affect the cytoplasmic cyclic AMP level, regardless of the
      presence or absence of forskolin, suggesting the absence of functional muscarinic
      M2 and/or M4 receptors in the swine myometrium. The receptor binding study
      indicated that circular muscle layers of the swine myometrium contained a single
      class of [3H]quinuclidinyl benzilate binding site (Kd = 0.92 nM; Bmax = 126.6
      fmol/mg protein). Specific binding was displaced by muscarinic receptor
      antagonists in the following order (with pKi value and Hill coefficient in
      parentheses): atropine (8.22 and 0.93) > 4-DAMP (8.18 and 0.94) > tropicamide
      (6.78 and 0.93) > pirenzepine (5.46 and 0.92) > AF-DX116 (5.12 and 0.94). The
      present results suggest that in circular muscle layers of the swine myometrium,
      exogenous and endogenous acetylcholine cause contraction through activation of
      muscarinic M3 receptors present on smooth muscle cells.

PMID- 10079009
TI  - Control of the phasic and tonic contractions of guinea pig stomach by a ryanodine
      sensitive Ca2+ store.
AB  - In some smooth muscle cells, the rise in intracellular Ca2+ as a result of a Ca2+
      influx via plasma membrane Ca2+ channels can activate a further increase in
      intracellular Ca2+ as a result of Ca2+ release from intracellular stores. This
      study examined the role of the Ca2+-induced Ca2+ release from the ryanodine
      sensitive intracellular Ca2+ stores in shaping the smooth muscle contractions of
      guinea pig stomach. The contractile activity of isolated muscle strips of the
      fundus, corpus and antrum region of the stomach was recorded under isometric
      conditions. Ryanodine, an activator of Ca2+-induced Ca2+ release, concentration
      dependently (10(-7)-3x10(-5) M) increased the tone of fundus and corpus strips.
      Ryanodine had a dual action on the phasic contractions of the antrum and corpus:
      increase by the low concentrations (up to 10(-6) M) and inhibition by the high
      concentrations (10(-6)-3x10(-5) M). Nifedipine (10(-5) M) completely inhibited
      the ryanodine (10(-6) M)-induced phasic contractions and only partly the
      ryanodine (3x10(-5) M)-induced tonic contractions. In the presence of 10(-5) M
      cyclopiazonic acid, a specific inhibitor of sarcoplasmic reticulum Ca2+-ATPase,
      ryanodine (3x10(-5) M) further increased the tone of the corpus and fundus
      strips. Ryanodine (3x10(-5) M) induced tonic contractions in the fundus and
      corpus precontracted by acetylcholine (10(-5) M), and inhibited the acetylcholine
      (10(-6) M)-induced phasic contractions in the antrum and corpus. Ruthenium red,
      an inhibitor of Ca2+-induced Ca2+ release, concentration dependently (10(-6)-10(
      4) M) decreased the tone and amplitude of the phasic contractions. The data
      obtained provide evidence for the participation of a sarcoplasmic reticulum Ca2+
      induced Ca2+ release mechanism in shaping the tonic and phasic contractions of
      guinea pig stomach, and highlight important tissue differences.

PMID- 10079010
TI  - Phosphodiesterase 4-dependent regulation of cyclic AMP levels and leukotriene B4
      biosynthesis in human polymorphonuclear leukocytes.
AB  - Several selective phosphodiesterase 4 inhibitors were found to be potent
      inhibitors of the N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene B4 biosynthesis
      by human polymorphonuclear leukocytes with IC50s in the nanomolar range (0.09-26
      nM). The rank order of potency was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline
      (RS-14203) > 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one
      (KF18280) > 8-aza-1-(3-nitrophenyl)-3-(4-pyridylmethyl)-2,4-quinazoline dione (RS
      25344) > 3-cyclo-pentyloxy-N-[3,5-dichloro-4-pyridyl]-4-methoxybenzamide (RP
      73401) > R-rolipram > R-4-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl]
      pyridine (CDP840)> S-rolipram. Isoproterenol (IC50 = 350 nM) and prostaglandin E2
      (IC50 = 59 nM) also suppressed leukotriene B4 biosynthesis. Inhibitors of the
      phosphodiesterase 1 (8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine (8-MeOMe
      IBMX)), phosphodiesterase 2 (erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA)),
      phosphodiesterase 3 (quazinone and milrinone) and phosphodiesterase 5 (zaprinast
      and dipyridamole) had no inhibitory effects on the fMLP-induced leukotriene B4
      biosynthesis (IC50s > 20 microM). All phosphodiesterase 4 inhibitors caused an
      accumulation of cellular cyclic AMP to 140-185% over the basal level of fMLP
      treated control cells, comparable to that observed with high concentrations of
      isoproterenol and prostaglandin E2. In contrast, the complete inhibition of
      leukotriene B4 production by 5-lipoxygenase and 5-lipoxygenase-activating protein
      (FLAP) inhibitors had no effect on cyclic AMP levels. Phosphodiesterase 1, 2, 3
      and 5 inhibitors had little effect on the level of cellular cyclic AMP (89-126%
      of the basal cyclic AMP level). Dose-dependencies for R-rolipram, RS-14203 and
      CDP840 indicated that the maximal accumulation of cyclic AMP occurred at
      concentrations of phosphodiesterase 4 inhibitors higher than those required for
      the inhibition of leukotriene B4 production. The presence of a mixture of 8-MeOMe
      IBMX, EHNA, milrinone and zaprinast to inhibit phosphodiesterase 1, 2, 3 and 5
      had little effect on the dose-dependence of R-rolipram for the inhibition of
      leukotriene B4 biosynthesis or cyclic AMP accumulation. These data demonstrate
      that selective phosphodiesterase 4 inhibitors can inhibit the fMLP-induced
      leukotriene B4 biosynthesis in human polymorphonuclear leukocytes with a potency
      similar or greater than that of potent 5-lipoxygenase or FLAP inhibitors. This
      inhibition is accompanied by small variations in the levels of cellular cyclic
      AMP and appears to proceed independently of the other phosphodiesterases.

PMID- 10079011
TI  - Central effects of cromoglycate sodium salt in rats treated with
      lipopolysaccharide.
AB  - In 24-h water- and food-deprived rats, we have evaluated the effects of
      cromoglycate sodium salt, an inhibitor of the mast cell degranulation with anti
      inflammatory and membrane-stabilizating activity, on the central effects induced
      by Escherichia coli lipopolysaccharide (LPS). Intraperitoneal (i.p.) injection of
      LPS (0.25, 0.50 and 1 mg/kg) induced a dose-dependent inhibition of water and
      food intake, fever, reduction in locomotor activity as well as increased anxiety
      levels. All these LPS effects were antagonized by a prior intracerebroventricular
      (i.c.v.) injection of cromoglycate sodium salt (100, 150 and 200 microg/rat). Our
      findings suggest that peripheral LPS administration may activate brain mast cells
      and indicate an involvement of these cells in brain pathophysiology.

PMID- 10079012
TI  - Participation of histamine H1 and H2 receptors in passive cutaneous anaphylaxis
      induced scratching behavior in ICR mice.
AB  - Scratching behavior associated with passive cutaneous anaphylaxis was examined
      and compared to that induced by compound 48/80 or histamine in ICR mice.
      Elicitation of passive cutaneous anaphylaxis, and intradermal injections of
      compound 48/80, histamine or serotonin induced both scratching behavior and
      vascular permeability increase in ICR mice. In mast cell-deficient WBB6F1-W/Wv
      mice, although histamine induced scratching behavior and vascular permeability
      increase, passive cutaneous anaphylaxis was not observed. Cetirizine and
      terfenadine significantly inhibited the scratching behavior and vascular
      permeability increase caused by passive cutaneous anaphylaxis, compound 48/80 and
      histamine. The histamine H1 receptor antagonists inhibited the vascular
      permeability increase almost completely, whereas they failed to abolish the
      scratching behavior. Famotidine and ranitidine significantly inhibited the
      scratching behavior caused by histamine. The histamine H2 receptor antagonists
      did not affect the vascular permeability increase caused by histamine. The
      combination of cetirizine and ranitidine abolished the histamine-induced
      scratching behavior. The combination, however, failed to potentiate the
      inhibition of passive cutaneous anaphylaxis-induced scratching behavior
      significantly. The results indicated that histamine induces scratching behavior
      in ICR mice through both histamine H1 and H2 receptors, and that histamine plays
      a major role in passive cutaneous anaphylaxis-induced scratching behavior.
      Histamine might also play an important role in compound 48/80-induced scratching
      behavior.

PMID- 10079013
TI  - Effects of the orally active non-peptide bradykinin B2 receptor antagonist,
      FR173657, on plasma extravasation in guinea pig airways.
AB  - We investigated the effect of the orally active non-peptide bradykinin B2
      receptor antagonist, FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2.4-di-chloro-3
      [(2-methyl-8-quinoli nyl)oxymethyl]phenyl]-N-methy-laminocarbonylmethyl]
      acrylamide), on plasma extravasation mediated by activation of sensory nerves in
      guinea pig airways. Plasma extravasation was assessed by the photometric
      measurement of the extravasated Evans blue after formamide extraction. We found
      that the increase in Evans blue dye extravasation evoked by an aerosol of
      bradykinin (0.1 mM, 2 min) in the presence of phosphoramidon (2.5 mg/kg, i.v.)
      was abolished completely by FR173657 (20 mg/kg, p.o.) in the trachea and main
      bronchi. In sensitized guinea pigs pretreated with phosphoramidon, FR173657 (20
      mg/kg, p.o.) inhibited plasma extravasation evoked by ovalbumin aerosol (5%, 2
      min) by 77+/-14.2% in the trachea and 65+/-11.2% in the main bronchi. FR173657
      (20 mg/kg, p.o.) did not affect the plasma extravasation caused by aerosolised
      capsaicin. These findings suggest that FR173657 is an orally active, promising
      anti-inflammatory agent for kinin-dependent inflammation following antigen
      challenge.

PMID- 10079014
TI  - Theaflavin-3,3'-digallate from black tea blocks the nitric oxide synthase by down
      regulating the activation of NF-kappaB in macrophages.
AB  - Nitric oxide (NO) plays an important role in inflammation and also in multiple
      stages of carcinogenesis. We investigated the effects of various tea polyphenols,
      including theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3'
      gallate, theaflavin-3,3'-digallate, thearubigin, and (-)-epigallocatechin-3
      gallate on the induction of NO synthase in lipopolysaccharide-activated murine
      macrophages, RAW 264.7 cells. Theaflavin-3,3'-digallate was found to be stronger
      than (-)-epigallocatechin-3-gallate in inhibiting NO generation and inducible NO
      synthase protein in activated macrophages, while theaflavin, a mixture of
      theaflavin-3-gallate and theaflavin-3'-gallate and thearubigin were less
      effective. Inhibition of NO production was observed when cells were cotreated
      with theaflavin-3,3'-digallate and lipopolysaccharide. Western blot and reverse
      transcriptase-polymerase chain reaction (RT-PCR) analyses demonstrated that
      significantly reduced 130-kDa protein and mRNA levels of inducible NO synthase
      were expressed in lipopolysacchride-activated macrophages with theaflavin-3,3'
      digallate, compared to those without theaflavin-3,3'-digallate. Electrophoretic
      mobility shift assay (EMSA) indicated that theaflavin-3,3'-digallate blocked the
      activation of nuclear factor kappaB (NF-kappaB), a transcription factor necessary
      for inducible NO synthase induction. Theaflavin-3,3'-digallate also blocked
      phosphorylation of IkappaB from cytosolic fraction and reduced lipopolysacchride
      induced nuclear accumulation of transcription factor NF-kappaB p65 and p50
      subunits. These results suggest that theaflavin-3,3'-digallate decreases the
      protein levels of inducible NO synthase by reducing the expression of inducible
      NO synthase mRNA, and the reduction could be via preventing the activation of NF
      kappaB, thereby inhibiting the induction of inducible NO synthase transcription.
      It was also demonstrated that the gallic acid moiety of theaflavin-3,3'-digallate
      is essential for their potent anti-inflammation activity.

PMID- 10079015
TI  - Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling
      pathway in T cells.
AB  - Tetrandrine, a purified traditional Chinese medicinal herb that acts as an
      immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat
      patients with arthritis, silicosis and hypertension. Since T cells play a
      critical role as autoreactive and pathogenic population in autoimmune diseases,
      in this study, we examined the immunosuppressive effect of tetrandrine on human
      peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12
      myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin
      2 secretion and the expression of the T cell activation antigen, CD71. Further
      investigation of the molecular mechanism demonstrated that tetrandrine inhibited
      the expression of the protein kinase C-dependent interleukin-2 receptor alpha
      chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69.
      Interestingly, when tetrandrine and cyclosporin A were added together,
      significant synergism in the suppression of T cell activation was observed.
      Moreover, of the several tetrandrine analogues studied, hernandezine was the most
      potent inhibitor of protein kinase C signaling events. These results also suggest
      that the protein kinase C-inhibitory capacity of tetrandrine and its analogues
      may not be associated with their function as Ca2+ channel blockers. Lastly, we
      showed that, within therapeutic concentrations, tetrandrine and its analogues
      could induce cellular apoptosis, which is defective in autoimmune diseases. In
      conclusion, our findings provide novel information about the molecular mechanism
      of the immunosuppressive effect of tetrandrine and its analogues in human
      peripheral blood T cells.

PMID- 10079016
TI  - Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in
      mice.
AB  - Rolipram is a type IV phosphodiesterase inhibitor endowed with powerful
      immunomodulatory properties. In this study, we evaluated the effects of this drug
      on the development of the T-cell-mediated hepatitis inducible in mice by
      concanavalin A. The results indicated that prophylactic treatment with either 5
      or 10 mg/kg rolipram injected intraperitoneally 24 h and 1 h prior to intravenous
      (i.v.) challenge with 20 mg/kg concanavalin A successfully ameliorated
      serological and histological signs of liver damage, so that the treated mice
      showed lower transaminase levels in the plasma and milder mononuclear cell
      infiltration of the liver as compared to vehicle-treated controls. Moreover, this
      effect was associated with profound modifications of circulating levels of
      cytokines released after concanavalin A injection, with the blood levels of
      interferon-gamma and tumor necrosis factor-alpha being significantly lower and
      those of interleukin-10 higher than those of the control mice. In particular, the
      increased blood levels of interleukin-10 might play an important role in the anti
      hepatitic effects of rolipram as coadministering this compound with anti
      interleukin-10 monoclonal antibody significantly reduced its anti-inflammatory
      action. These results suggest that rolipram may be useful in the clinical setting
      for the treatment of cell-mediated immunoinflammatory diseases such as
      immunoinflammatory hepatitis.

PMID- 10079017
TI  - Novel potent AMPA analogues differentially affect desensitisation of AMPA
      receptors in cultured hippocampal neurons.
AB  - The agonist actions of two AMPA receptor analogues, (RS)-2-amino-3-(3-carboxy-5
      methyl-4-isoxazolyl)propionic acid (ACPA) and (RS)-2-amino-3-(3-hydroxy-5
      trfluoromethyl-4-isoxazolyl)prop ionic acid (Tri-F-AMPA) have been studied on
      cultured rat hippocampal neurons. Whole-cell recordings with semi-rapid
      application of the agonists were used to study steady-state (plateau) responses.
      ACPA was the most potent agonist (EC50, 1.2 microM), followed by AMPA (4.3
      microM) and Tri-F-AMPA (4.6 microM), corresponding to a potency ratio of 4:1:1.
      Hill coefficients were close to 1 for AMPA and ACPA and close to 2 for Tri-F
      AMPA, respectively. Plateau responses to maximal concentrations of the three
      agonists varied more than 2-fold. ACPA responses were 2.1 times greater and
      responses to Tri-F-AMPA were 1.6 times greater than responses to AMPA,
      respectively. Peak responses and desensitization were studied by using a fast
      piezoelectric device to apply agonists rapidly to outside-out patches. The time
      constants of desensitization were 8 ms for AMPA, 12 ms for Tri-F-AMPA and 17 ms
      for ACPA. There were no significant differences in the time-to-peak and 10-90%
      rise-time of the responses. The results indicate that of the three agonists
      tested, ACPA is the most potent at AMPA receptors expressed in cultured
      hippocampal neurons and that the maximum response to the agonists is inversely
      related to the rate of desensitization.

PMID- 10079018
TI  - Binding of the antagonist [3H]candesartan to angiotensin II AT1 receptor
      transfected [correction of tranfected] Chinese hamster ovary cells.
AB  - Binding of the non-peptide angiotensin II AT1 antagonist [3H](2-ethoxy-1-[(2'-(1H
      tetrazol-5-yl)biphenyl-4-yl)methyl]- H-benzimidazoline-7-carboxylic acid
      ([3H]candesartan) to human angiotensin II AT1 receptor-transfected Chinese
      hamster ovary (CHO-AT1) cells was inhibited to the same extent by angiotensin II
      and non-peptide angiotensin II AT1 antagonists. No binding was observed in
      control CHO-K1 cells. Dissociation was slow (k(-1) = 0.0010+/-0.0001 min(-1))
      after removal of the free [3H]candesartan but increased 5-fold upon addition of
      supramaximal concentrations of angiotensin II AT1 antagonists. Angiotensin II
      responses recovered equally slow from candesartan-pretreatment. When washed and
      further incubated, these angiotensin II responses also recovered more rapidly in
      the presence of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5
      yl)biphen yl-4-yl)methyl]imidazole (losartan), indicating that unlabelled ligands
      prevented reassociation. [3 H]candesartan saturation binding experiments required
      a long time to reach equilibrium. Therefore, the equilibrium dissociation
      constant (Kd = 51+/-8 pM) was calculated from the association and dissociation
      rate constants. Our findings indicate that the insurmountable nature of
      candesartan in functional studies is related to its slow dissociation from the
      receptor.

PMID- 10079019
TI  - Inhibition of serum deprivation- and staurosporine-induced neuronal apoptosis by
      Ginkgo biloba extract and some of its constituents.
AB  - Previous studies have already demonstrated that some constituents of an extract
      of Ginkgo biloba (EGb), such as ginkgolide B and bilobalide, protect cultured
      neurons from hypoxia- and glutamate-induced damage. This prompted us to
      investigate whether they were also able to inhibit neuronal apoptosis. We induced
      apoptosis in cultured chick embryonic neurons as well as in mixed cultures of
      neurons and astrocytes from neonatal rat hippocampus by serum deprivation and
      staurosporine. The increase in the percentage of apoptotic chick neurons from 12%
      in controls to 30% after 24 h of serum deprivation was reduced to control level
      by EGb (10 mg/l), ginkgolide B (10 microM), ginkgolide J (100 microM) and
      bilobalide (1 microM). After treatment with staurosporine (200 nM) for 24 h we
      observed 74% apoptotic chick neurons. This percentage of apoptotic neurons was
      reduced to 24%, 62% and 31% in the presence of EGb (100 mg/l), ginkgolide J (100
      microM) and ginkgolide B (10 microM), respectively. Bilobalide (10 microM)
      decreased apoptotic damage induced by staurosporine treatment for 12 h nearly to
      the control level. In mixed neuronal/glial cultures, the extract of EGb (100
      mg/l) and bilobalide (100 microM) rescued rat neurons from apoptosis caused by
      serum deprivation, whereas, bilobalide (100 microM) and ginkgolide B (100 microM)
      reduced staurosporine-induced apoptotic damage. Ginkgolide A revealed no anti
      apoptotic effect in either serum-deprived or staurosporine-treated neurons. Our
      results suggest that EGb and some of its constituents possess anti-apoptotic
      capacity and that bilobalide is the most potent constituent.

PMID- 10079020
TI  - LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta
      adrenoceptors.
AB  - LK 204-545 ((+/-)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2
      hydro xy-propyl-amino)-ethyl)-3-(4-hydrxy-phenyl) urea), an antagonist that
      possesses high beta1-/beta2-selectivity in the rat, and a range of cardio
      selective and non-selective beta-adrenoceptor antagonists were examined to
      compare their radioligand binding affinities for human beta1-, beta2- and beta3
      adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the
      highest beta1-/beta2- (approximately 1800 and approximately 650, respectively)
      and beta1-/beta3-selectivity (approximately 17000 and approximately 2200,
      respectively) at human beta-adrenoceptors with LK 204-545 being approximately
      2.75-fold more beta1-/beta2-selective and approximately 8-fold beta1-/beta3
      selective than CGP 20712A. The high potency of LK 204-545 at transfected human
      beta1-adrenoceptors and in functional models of rat beta1-adrenoceptors together
      with its high selectivity, identify it as a useful ligand for studying beta1
      adrenoceptors and suggest that it may be the preferred ligand for human beta
      adrenoceptor studies.

PMID- 10079021
TI  - Nongenomic steroid actions: completing the puzzle. Aldosterone as an example.
AB  - In the common unidimensional theory of steroid action, steroids bind to
      intracellular receptors and modulate nuclear transcription and thus protein
      synthesis. These genomic steroid effects, being characterized by their delayed
      onset of action and their dependence on transcription and protein synthesis, have
      been known for several decades. In contrast, very rapid actions of steroids,
      which are considered to be of nongenomic origin, have been recognized more widely
      and characterized in detail only during the past ten years. Specific rapid
      effects of steroids and related hormones like vitamin D3 and thyroid hormones on
      cellular function involve a conventional second messenger cascade which in most
      cases includes phospholipase C, phosphoinositide turnover, intracellular pH and
      intracellular calcium ([Ca2+]i), and protein kinase C. Furthermore, binding sites
      in membranes have been characterized exposing binding features compatible with an
      involvement in rapid-steroid signaling. Characteristics of putative membrane
      receptors are completely different from those of classic intracellular steroid
      receptors; this also includes the inability of classic steroid receptor
      antagonists to inhibit those rapid nongenomic steroid actions. The physiological
      and pathophysiological relevance of these effects is still largely unclear, but
      their existence has been proven recently even under in vivo conditions. New drugs
      modulating nongenomic steroid actions may find applications in various areas such
      as the cardiovascular and central nervous systems, infertility and electrolyte
      homeostasis. This short review focuses mainly on the nongenomic actions of
      aldosterone and their cardiovascular implications.

PMID- 10079022
TI  - Clinical and molecular aspects of androgen receptor defects.
AB  - The androgen receptor (AR) is a ligand-dependent transcription factor involved in
      various biological processes such as sex differentiation, sexual maturation and
      spermatogenesis. Disorders of AR function cause a wide spectrum of androgen
      insensitivity syndromes. The phenotypes vary from women with female external
      genitalia through patients with genital ambiguity to men with normal male
      genitalia but infertile. The CAG repeat in exon A is important for
      transactivation function of the AR and consequently for many androgen-dependent
      processes. Expansion of this repeat is the cause of the X-linked spinal and
      bulbar muscular atrophy (SBMA, Kennedy's disease). Mutations of the AR gene occur
      commonly in prostate cancers and are significant for prognosis of the disease.

PMID- 10079023
TI  - Microvascular skin blood flow following the ingestion of 75 g glucose in healthy
      individuals.
AB  - It is expected that microvascular blood flow might be affected by blood glucose,
      blood insulin and C-peptide levels. In our investigation skin microvascular blood
      flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37
      degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten
      healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight.
      The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous
      oxygen electrode at a temperature of 44 degrees C. The microvascular response to
      acetylcholine was investigated before the start of the ingestion period and after
      30 minutes. In addition, the capillary blood cell velocity (CBV) was measured
      using dynamic capillaroscopy. During OGT an increase in LDF could be observed at
      37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44
      degrees C (86%, n.s.). The microvascular response to acetylcholine increased by
      164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT
      investigation. No significant changes in the microvascular measurements could be
      observed during the water experiment. No significant changes could be observed in
      the CBV measurements in any phase of the investigation. Plasma C-peptide and
      insulin levels exhibited an association with the LDF measurements at 37 degrees C
      (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar
      values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01).
      After the ingestion of glucose a sophisticated modulation of microvascular blood
      flow was found in healthy volunteers. Further studies are necessary to
      investigate the role of a disturbed postprandial blood sugar control, insulin and
      C-peptide secretion in the development of microvascular dysfunction, especially
      in IDDM.

PMID- 10079024
TI  - Cardiovascular risk profile after simultaneous pancreas and kidney
      transplantation.
AB  - The positive influence of simultaneous pancreas and kidney transplantation (PKT)
      on the development of diabetic microvascular lesions is well established. On the
      other hand, little is known on its impact on diabetic macrovascular disease,
      which is still the major cause of death in diabetes, including patients after
      PKT. In order to evaluate the influence of PKT on the cardiovascular risk
      profile, we performed a cross-sectional study on 55 patients. Special attention
      was given to the hemorheological parameters fibrinogen and plasma viscosity, two
      important cardiovascular risk factors, which so far have found no attention in
      the field of PKT research. The patients were subdivided into three groups
      according to their graft function: group 1-26 patients after successful PKT (no
      insulin dependency, serum creatinine <2 mg%), group 2-23 patients after PKT and
      rejection of the pancreas graft (insulin dependency, serum creatinine <2 mg%),
      group 3-6 patients after PKT with pancreas rejection and renal insufficiency
      (insulin dependency, serum creatinine >2 mg%, no dialysis). There was a high
      prevalence of arterial hypertension after PKT (group 1: 65%, group 2: 70%, group
      3: 100%). Serum lipids were in the normal range as long as renal function was
      intact. In renal insufficiency, however, LDL-cholesterol and triglycerides were
      significantly elevated (p < 0.05). Fibrinogen was significantly raised after PKT
      (p < 0.001), as was plasma viscosity when the pancreas graft was rejected (p <
      0.02). There was a tendency towards elevated fibrinogen levels with decreasing
      graft function. In conclusion, a number of cardiovascular risk factors were
      identified in patients after PKT, predominantly arterial hypertension and
      impaired hemorheology, with elevated fibrinogen levels and plasma viscosity.
      There is a further enhancement with decreasing graft function.

PMID- 10079025
TI  - Glucose concentration in human subcutaneous adipose tissue: comparison between
      forearm and abdomen.
AB  - There is still controversy about the relation between the glucose concentration
      in the subcutaneous (sc.) adipose tissue and the blood plasma. Depending on the
      technique applied, the glucose concentration in sc. tissue varies between 50% and
      100% of the plasma glucose concentration. In the present study the sc. glucose
      concentration of forearm and abdomen in seven healthy volunteers was compared
      with plasma glucose by applying the microdialysis technique with very low flow
      rates. A microdialysis probe implanted into the subcutaneous tissue of abdomen
      and forearm was perfused with a flow rate of 1 microl/4 min. The dialysate was
      sampled in three 2-h-fractions in the fasting state and in one 2-h-fraction
      during a hyperglycemic clamp (216.9+/-3.4 mg/dl) (mean +/- SEM). The mean
      recoveries of the plasma glucose were 91.1+/-4.1% in the forearm and 82.7+/-18.0%
      in the abdomen. The recoveries in the sc. tissue of abdomen and arm were not
      significantly different. However, the arm showed significantly (p < 0.014) less
      interindividual variance (range 73.2- 103.2%) than the abdomen (range 50.6
      117.1%) and appears to be the preferable implantation site. The recovery remained
      constant during the investigation.

PMID- 10079026
TI  - Reduced insulin-mediated glucose uptake by euglycemic clamp in offspring of
      patients with type 2 diabetes.
AB  - Family studies point to an important genetic element in the genesis of type 2
      diabetes. A variety of metabolic abnormalities have been documented in offspring
      of patients with type 2 diabetes. It has not been shown, however, at what age
      reduced insulin sensitivity is demonstrable using the sensitive the euglycemic
      clamp technique. To address this issue we screened 425 consecutive type 2
      diabetic patients and examined all available (n = 48) normotensive,
      normoglycemic, non-smoking offspring (mean age 31.4+/-0.9 years) and compared
      them to 22 healthy offspring of non-diabetic parents (controls). The two groups
      were of similar age and BMI. Measurements in offspring and controls included
      baseline IRI, tissue glucose uptake (TGU, using euglycemic hyperinsulinemic clamp
      technique), and 24 hour ambulatory blood pressure (ABP). TGU was significantly (p
      < 0.001) lower in offspring of diabetic parents (338.8+/-19.9 (mol/kg/min) when
      compared to controls (516.6+/-22.2 micromol/kg/min). 24 h systolic ABP was
      significantly higher (p < 0.02) in propositi compared to controls (121.2+/-2.2 mm
      Hg and 113.8+/-1.7 mm Hg, respectively). No difference in triglycerides
      concentration was found. A borderline negative correlation was observed, however,
      between triglyceride levels and TGU (R = -0.48, p < 0.001). TGU was not related
      to the presence or absence of diabetic nephropathy in the parents. We conclude:
      Insulin resistance and various facets of the metabolic syndrome are demonstrable
      even at age 30 years in young non-obese, normotensive offspring of patients with
      type 2 diabetes. These disturbances are not related to the presence of
      microvascular complications in parents.

PMID- 10079027
TI  - The effect of clozapine on glucose metabolism.
AB  - Although there have been several reports that clozapine precipitated
      hyperglycemia and diabetic ketoacidosis in some patients, the mechanism by which
      clozapine impairs glucose metabolism is not known. This study investigated the
      effect of clozapine on glucose metabolism in six schizophrenic patients while
      they were free of medication and receiving 200 mg/d and 450 mg/d of clozapine.
      Clozapine increased mean levels of blood glucose, insulin and C-peptide. It is
      possible, based on these findings, that the glucose intolerance was due to
      increased insulin resistance.

PMID- 10079028
TI  - Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice.
AB  - Apoptosis appears to play an important role in the development of diabetes in the
      non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the
      manifestation of insulin dependent diabetes mellitus (IDDM) can also affect the
      sympathochromaffin system, we analyzed the role of apoptosis and infiltration of
      the adrenal medulla as features of this autoimmune process in parallel with the
      development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks
      were studied and compared with control mice. Apoptosis was assessed by in situ
      end-labeling method and ultrastructural analysis. Adrenals were screened for
      lymphocytic infiltration by conventional hematoxylin-eosin staining. Chromaffin
      cells were characterized by immunohistochemical staining against synaptophysin
      and tyrosine hydroxylase. Apoptotic nuclei were detected in all mice studied at a
      very low level, mainly occuring within the connective tissue between medulla and
      cortex. The maximum score was achieved at 3 weeks (1.91+/-0.48 apoptotic
      cells/1000 counted cells; n = 4). There was no significant difference between NOD
      mice and control mice. No correlation could be found between blood glucose levels
      and apoptosis. On the ultrastructural level, apoptotic cells presented typical
      features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice
      nor in controls lymphocytic infiltration or fibrosis of the adrenal was detected.
      Even NOD mice with overt diabetes did not exhibit morphological signs of
      medullitis. In summary, no signs of immune destruction of the adrenal medulla in
      NOD mice aged 3 to 30 weeks could be detected.

PMID- 10079029
TI  - Impaired expression of brain natriuretic peptide gene in diabetic rats with
      myocardial infarction.
AB  - Accordingly, we induced streptozotocin diabetes in rats and evaluated the effects
      of ligating the coronary artery to produce myocardial infarct by analyzing
      hemodynamics and the expression of brain natriuretic peptide (BNP) messenger (m)
      RNA. Eight-week diabetic rats and age-matched nondiabetic rats underwent ligation
      of the coronary artery for 1 week. Left ventricular end-diastolic pressure
      (LVEDP) was not statistically different between diabetic rats (15+/-6 mmHg) and
      nondiabetic rats (13+/-9 mmHg) 1 week after coronary ligation, size of infarct,
      systolic blood pressure were also similar in both groups after coronary ligation.
      The BNP mRNA/beta-actin mRNA ratio in right ventricle of nondiabetic rats with MI
      was increased to 350+/-60%, however, in diabetic rats with MI, that was slightly
      increased to 200+/-50% (P < 0.01). The level of BNP mRNA in the left ventricle of
      diabetic rats with MI was not increased significantly (120+/-30% versus that in
      diabetic rats without MI), although that in left ventricle of nondiabetic rats
      with MI was increased to 280+/-40% versus nondiabetic rats without MI (P < 0.01).
      Cardiac BNP synthesis in diabetic rats completely reverted to control levels
      after insulin therapy.

PMID- 10079030
TI  - T3-release from autonomously functioning thyroid nodules in vitro.
AB  - Toxic thyroid nodules have been shown to be of clonal origin. In a portion of
      them, point mutations affecting either the gene of the TSH receptor (TSHr) or the
      alpha-subunit of stimulating G-protein, consecutively leading to enhanced cAMP
      levels, which may enhance growth or functional activity of the thyrocyte or both,
      were recently found. To complement these studies, we evaluated hormone response
      (i.e. T3 release) in vitro from tissues derived from toxic thyroid nodules as
      compared directly to the surrounding paranodular tissues as well as tissues
      derived from euthyroid goiter and from patients with Graves' disease. Experiments
      were conducted in the presence and absence of bTSH or Graves' immunoglobulines.
      Tissues obtained during surgery were incubated over 5 h, followed by equilibrium
      dialysis for 24 h, and determination of free T3 in an aliquot by RIA. Basal T3
      release in nodular tissues (n = 10) was significantly higher (median: 7.3 ng/l)
      compared to paranodular tissues (3.2 ng/l; P < 0.01), tissues derived from
      euthyroid goiter (1.3 ng/l; n = 12; P < 0.001) and thyroid tissues derived from
      patients with Graves' disease (2.5 ng/l; n = 6; P < 0.001). Upon stimulation with
      bTSH (1 IU/l), median T3 concentrations markedly increased to 11.5 ng/l (P <
      0.05), 7.3 ng/l (P < 0.05), 4.2 ng/l (P < 0.01) and 3.2 ng/l (P = N.S.),
      respectively. Stimulation over basal values was 1.6-fold in nodular tissues, 2.3
      fold in paranodular tissues, 3.2-fold in euthyroid goiter and 1.3-fold in Graves'
      disease. In toxic thyroid nodules basal hormone-releasing activities were
      stimulated by fifteen out of twenty (75%) Graves' sera tested. For comparison,
      stimulation in other tissues occurred in 45% (paranodular), 80% (euthyroid
      goiter) and 35% (Graves' disease), respectively. In conclusion, tissue derived
      from toxic thyroid nodules exhibits enhanced basal hormone release as compared to
      both, the surrounding paranodular tissues and tissues from euthyroid goiter in
      vitro, which may reflect constitutional activation of TSHr, alpha-subunit of
      stimulating G-protein or other so far unknown intermediate by point mutations
      affecting the respective genes. Hyperactivities in toxic thyroid nodules may be
      even further enhanced by external stimulators such as TSH or TSH receptor
      antibodies. The first stimulator may have clinical relevance in patients with
      toxic thyroid nodules and not yet suppressed TSH; the latter could play a role in
      the rare Marine Lenhart syndrome.

PMID- 10079031
TI  - Residual effects of thyroid hormone on secretory activity of somatotroph
      population.
AB  - In the present experiments the effects of the interruption of a prolonged T3
      treatment on somatotroph population and GH synthesis and secretion were studied.
      The treatment with pharmacological doses of T3 provokes marked ultrastructural
      changes in somatotrophs compatible with a stimulated synthesis of GH. These
      results can be correlated with the significant increase in pituitary GH content
      and the normal values of serum GH. Twenty-four hours after T3 withdrawal,
      somatotrophs exhibited a marked depletion of secretory granules by exocytosis.
      These changes were concurrent with a significant discharge of pituitary GH and a
      two-fold increase in GH serum levels. The serum concentrations attained the
      highest values on the second and the third day after the T3 suppression, while
      the pituitary GH contents recovered the control levels. Morphometry of
      somatotroph population revealed a clear proliferation of cells and increased
      areas immunostained for GH, 24 h after withdrawal of the T3 treatment. The
      effects of T3 on somatotrophs were persistent for several days and at least five
      days were required for all parameters to return to control values. These results
      provide a new insight on the residual activity of thyroid hormones on both
      functional activity and morphological organization of somatotrophs.

PMID- 10079032
TI  - Preovulatory secretion of steroids by cultured cumulus oophorus complexes of the
      rat: effects of FSH and LH.
AB  - The main objective of the present study was to establish whether a shift in
      steroid production, previously observed for preovulatory follicles, also takes
      place in preovulatory cumulus oophorus complexes (COCs). Female Wistar rats,
      displaying a regular 4-day oestrous cycle, were killed in succession every 2 or 3
      h on the day of prooestrus and oestrus until ovulation (11.00-24.00 h). From
      excised ovaries preovulatory follicles were isolated. After puncturing cumuli
      oophori were aspirated and subsequently cultured for 24 h either in hormone-free
      or FSH- or LH- or FSH plus LH-supplemented medium. Cultured COCs released only a
      small amount of androgens, the main steroid produced being oestradiol. Its
      secretion decreased before ovulation (24.00 h). Relatively high progesterone
      release occured only in cultures set up at 22.00 and 24.00 h, thus during cumulus
      expansion. FSH and LH present in the medium effected above all oestradiol
      release, stimulating it before the presumptive endogenous gonadotrophin surge and
      inhibiting it thereafter. The activity of delta5-3beta-hydroxysteroid
      dehydrogenase (3betaHSD) investigated in cryostat sections appeared in COCs at
      22.00h and was still present at 24.00 h. However, the activity was much weaker
      than in the granulosa cells lining the basal lamina. This in vivo study confirms
      in vitro results on more intense progesterone synthesis during cumulus expansion.
      The results indicate that in preovulatory COCs a shift in steroid production
      occurs after which the main steroid synthesized is progesterone, while oestradiol
      secretion decreases. However, this switch in COCs takes place later than the
      previously established shift in whole follicles.

PMID- 10079033
TI  - Quantification of insulin-like growth factor-1 (IGF-1) mRNA: development and
      validation of an internally standardised competitive reverse transcription
      polymerase chain reaction.
AB  - To investigate the role of local IGF-1 mRNA expression in various tissues, we
      developed and validated a method which allows for a specific, sensitive and
      reliable quantification of IGF-1 mRNA: an internally standardised Reverse
      Transcription-Polymerase Chain Reaction (RT-PCR). A synthetic competitive
      template IGF-I standard cRNA (IGF-1 cRNA) was designed, which contains the same
      flanking primer sequences used to amplify the wild type IGF-1 mRNA, but differs
      by 56 bp in length. To obtain the IGF-1 mRNA concentration present in tissue RNA
      samples, series of 250 ng total-RNA were spiked with three known quantities of
      the standard IGF-1 cRNA, incubated for competitive RT-PCR reactions and the two
      amplificates obtained (184 bp from IGF-1 cRNA and 240 bp from the wild type IGF-I
      mRNA) were subsequently separated and quantified by HPLC-UV. For every individual
      tissue RNA sample, the ratio R (R = competitor PCR product / wild type PCR
      product) was plotted against the number of starting molecules of the competitor
      IGF-1 cRNA. The initial amount of IGF-1 mRNA present in the sample can then be
      read off where R = 1. The validated assay had a detection limit of 1600 IGF-1
      cRNA molecules/reaction, the intra-assay variation was 7.4% (n = 5) and linearity
      (r = 0.997) was given between 140 ng to 840 ng total-RNA input. The present
      method was first applied to study the effect of long term castration on the IGF-1
      expression rates in bovine tissues. The hepatic IGF-1 mRNA concentrations were
      well correlated (r = 0.81) with the plasma concentrations as quantified by RIA
      and were higher in intact than in castrated animals. In two skeletal muscles (m.
      splenius and m. gastrocnemius) IGF-1 mRNA concentrations were 20- and 35- times
      lower than in liver, respectively, without any differences between steers and
      bulls. In bulls, the IGF-1 mRNA expression was higher in m. splenius (p < 0.01)
      than m. gastrocnemius, indicating that locally produced IGF-1 might be important
      for sexually dimorphic muscle growth patterns.

PMID- 10079034
TI  - Quantification of insulin-like growth factor-1 (IGF-1) mRNA: modulation of growth
      intensity by feeding results in inter- and intra-tissue-specific differences of
      IGF-1 mRNA expression in steers.
AB  - The effect of constant and compensating body growth velocities on IGF-1 mRNA
      expression was studied in various tissues of growing steers. Twenty-six steers
      were allocated to three groups in which the average daily gains were kept either
      constantly high on intensive feeding, low on pasture feeding or were accelerated
      to compensatory growth after feed restriction. All animals were slaughtered at
      570+/-2.6 kg and samples were collected from liver, heart, kidney and from 4
      different muscles (m. splenius, m. soleus, m. cutaneus truncii and m.
      semispinalis capitis), which were selected in order to include maximal
      differences in fibre composition as well as in growth impetus. IGF-1 mRNA was
      quantified by a validated internally standardised RT-PCR method. The amount of
      RNA extracted from the various tissues investigated was constant within each type
      of tissue and showed no differences between treatment groups. As indicated by a
      constant ratio between the amount of RNA extracted and the DNA concentrations,
      there was no effect of the feeding on total transcriptional activity. The order
      of IGF-1 mRNA abundance per g tissue was liver > > kidney > heart > skeletal
      muscle. The different feeding regimen resulted in significant differences of IGF
      1 mRNA expression rates in all organs showing different patterns between organs.
      IGF-1 mRNA concentrations showed muscle specific differences and also divergent
      reactions in response to the differing growth rates. These results support that
      the liver is the main IGF-1 producing tissue; above that they indicate that
      skeletal muscle, in particular when taking its absolute mass into account, might
      considerably contribute to the IGF-1 levels in blood. Our findings demonstrate
      that IGF-1 mRNA expression is regulated tissue specifically not only between
      different organs but also within musculature.

PMID- 10079035
TI  - Expression of leptin receptor mRNA and the long form splice variant in human
      anterior pituitary and pituitary adenoma.
AB  - Expression of leptin receptor (OB-R) mRNA was detected in the human anterior
      pituitary as well as in ACTH-secreting and nonsecreting pituitary adenomas by RT
      PCR with primers recognizing all receptor splice variants. Primers specific to
      the long splice variant of the leptin receptor (OB-Rb), containing the putative
      intracellular signalling domain, also revealed a strong expression in normal and
      adenomatous anterior pituitaries. These results indicate that the pituitary is a
      possible target tissue of leptin action and might be involved in leptin
      regulation of pituitary hormone secretion.

PMID- 10079036
TI  - Residual vision in transition zones in patients with cerebral blindness.
AB  - Using high resolution perimetry in repeated sessions, we investigated 27 patients
      with homonymous visual field defects in order to detect islands of vision within
      the damaged area, and to determine color- and form-recognition abilities within
      these zones of residual vision. In most patients we found circumscribed areas
      within the "blind" field in which the stimulus was detected in about 50% of
      presentations. Only one patient had an island of vision greater than 5 degrees
      within the defective area. We also found an area of variable performance between
      the blind and the intact field. Borders of field defects were classified as
      being: (a) sharp (small transition zone), (b) medium, or (c) fuzzy (scattered
      deficits). We propose that transition zones are functional representations of
      partially spared neuronal structures in areas of the brain which are only
      partially injured.

PMID- 10079037
TI  - Perception of transplanted toes following toe-to-finger transplantation.
AB  - The perception of transplanted toes following toe-to-finger transplantation was
      investigated. Forty-six (77%) of 60 patients perceived transplanted toes as their
      fingers immediately or within 6 months after surgery. Such perception occurred
      following satisfactory surgical outcome, the appearance of adequate sensory or
      motor function, or both. In the remaining 14 patients, the transplanted toe was
      perceived as a toe, a toe as well as a finger, or something else. The present
      data suggest that human perception of transplanted toes appears to be geared
      toward restoration of the original body image.

PMID- 10079038
TI  - Detecting simulated memory impairment with the Rey Auditory Verbal Learning Test:
      implications of base rates and study generalizability.
AB  - The accuracy of the Rey Auditory Verbal Learning Test (RAVLT) for detecting
      simulated neuropsychological impairment was investigated using discriminant
      function analyses and cross-validation procedures. In Study 1, a discriminant
      function analysis, using six RAVLT variables, correctly classified 80% of 50
      simulating and 50 non-simulating participants. Base rates were changed and this
      discriminant function was tested in Study 2 with a 33% base rate of simulation.
      The discriminant function correctly classified 75% of 20 simulators and 90% of 40
      non-simulators, yielding an overall classification rate of 85%. To determine the
      generalizability of this discriminant function to a clinical sample, Study 3
      compared the RAVLT performance of 20 simulating participants to that of 40 motor
      vehicle accident (MVA) patients. The discriminant function from Study 1
      incorrectly classified 60% of the MVA patients and yielded an overall correct
      classification rate of 48%. The limitations associated with generalizing from
      analog research and the implications of varying base rates on classification
      accuracy are discussed.

PMID- 10079039
TI  - Clinical assessment of psychopharmacological treatment of preschoolers with ADHD.
AB  - Sixteen preschoolers, (8 with Attention-Deficit/Hyperactivity Disorder [ADHD], 8
      matched controls) were assessed twice, 5 months apart. Preschoolers with ADHD
      were rated by their parents as significantly more inattentive, exhibited more
      behavior problems, fewer age-appropriate social skills, made more errors of
      omission on both the visual and auditory attention tests, and more errors of
      commission on both the visual attention and the visual-search cancellation tests.
      Preschoolers with ADHD were then treated with stimulant medication and exhibited
      improved behavior as well as significantly reduced errors of omission on visual
      and auditory preschool vigilance tests, and fewer errors of commission on the
      visual-search preschool cancellation test. Developmentally appropriate direct
      measures of attention, in conjunction with parental ratings of child behavior,
      can be used to assess the efficacy of pharmacological treatment of preschoolers
      with ADHD.

PMID- 10079040
TI  - Analyses of deficits in gestural pantomime.
AB  - The frequency and characteristics of apraxia in 63 stroke patients with left- or
      right-hemisphere damage were examined. Analyses focussing on five dimensions of
      gestural performance revealed an overall frequency of apraxia of 54% in patients
      with LHD and 30% in patients with RHD. Although both groups were impaired on the
      orientation and hand posture dimensions of performance, the patients with RHD
      exhibited significantly poorer performance on the location dimension and the
      patients with LHD on the action dimension. Analyses of intrahemispheric lesion
      localization implicated damage to subcortical areas involving periventricular
      white matter tracts at the temporoparietal junction with apraxia.

PMID- 10079041
TI  - Sustained attention and impulsivity in children with Tourette syndrome:
      comorbidity and confounds.
AB  - We sought to determine whether Tourette syndrome (TS) was related to attentional
      disturbance independent of Attention Deficit Hyperactivity disorder (ADHD) and
      obsessive-compulsive symptoms (OCS), two comorbid conditions associated with
      attentional problems in other populations. Participants were 74 children [21 with
      uncomplicated TS (TS-Only), 14 with TS and ADHD (TS-ADHD), 21 with ADHD, and 18
      controls]. Impaired sustained attention and impulsivity on a Continuous
      Performance Task were uncommon in the TS-Only group, but common in TS-ADHD and
      ADHD. The TS-ADHD group was less impulsive than the ADHD group, but had a higher
      rate of whole-body tics than the TS-Only group, raising questions about the
      diagnosis of ADHD in TS. OCS was not an independent risk factor for attention
      problems. However, the association of tic severity and impulsivity was consistent
      with the theory that TS involves dysfunction in cortical-subcortical circuits
      mediating behavioral inhibition.

PMID- 10079042
TI  - Multinational neuropsychological testing: performance of children and adults.
AB  - We obtained neuropsychological assessment data on persons from five countries
      whose ages range from 8 to 90 years. Participants were assessed in four
      languages. The results from the multivariate analyses indicate that reaction-time
      measures obtained in tests of sustained attention are minimally affected by
      country of origin and level of education. In contrast, tests assessing the
      ability to focus attention and solve a problem, to shift strategies, and to
      inhibit an automatic response tendency differ significantly by country and level
      of education. Most of these differences tend to disappear at about the age of 54.
      The data provide partial support for the hypothesis of commonality of some
      neuropsychological functions across cultures.

PMID- 10079043
TI  - Profiles of patients with left prefrontal and left temporal lobe lesions after
      cerebrovascular infarcations on California Verbal Learning Test-like indices.
AB  - We compared memory disorders of three patient groups suffering from brain lesions
      with a word list corresponding to the California Verbal Learning Test (CVLTgcor).
      Dependent measures were learning rate and efficiency, retention, and strategic
      control of the learning process. Compared to a control group of patients with
      right hemispheric lesions, a left Arteria cerebri posterior (LACP) group showed
      general memory deficits, an inflated recency effect, and increased serial
      clustering. A left prefrontal cortex (LPFC) group documented slowed learning and
      increased recall after semantic cues. Discriminant analysis correctly classified
      86.11% of the patients. It is argued that (a) the CVLT helps to cover differences
      in memory disorders recently discussed in cognitive neuropsychology; (b)
      differences between PFC and ACP patients become evident only if strategic aspects
      of learning and increased recall after semantic cueing are taken into account.
      The results are discussed within the framework of recent cognitive
      neuropsychological findings and with a distinction between fronto-subcortical and
      cortical memory disorders.

PMID- 10079044
TI  - Neuropsychological function in patients with nasopharyngeal carcinoma after
      radiotherapy.
AB  - A neuropsychological test battery was administered to 27 adult patients with
      nasopharyngeal carcinoma (NPC) who had received radiotherapy, 28 adult patients
      with NPC awaiting radiotherapy, and 35 normal adult controls. The 27 patients
      with radiotherapy had a conventional dosage, 220 cGy per fraction, or less. The
      median interval between the completion of radiotherapy and the evaluation of
      neuropsychological function was 1.7 years. Groups were matched for age and
      educational level. The results showed that our NPC group with radiotherapy had
      neuropsychological impairments in the areas of auditory attention/concentration,
      immediate and delayed verbal recall and immediate visual recall, and recent
      memory, higher-order visuospatial abilities, and bimanual dexterity. Thus
      neuropsychological dysfunction may occur in patients with NPC within the first 2
      years after radiotherapy.

PMID- 10079045
TI  - Self- and informant-ratings on the patient competency rating scale in patients
      with traumatic brain injury.
AB  - The Patient Competency Rating Scale (PCRS) provides self- and informant-ratings
      of everyday memory and gives a guide to patients' awareness of their
      difficulties. Research using the PCRS has focussed on groups with severe TBI and
      little is known about ratings of functioning in other severity groups or in a non
      TBI population. In the current study the TBI group (n = 53) overrated their pre
      accident competency compared to controls (n = 131). Patients with severe TBI (n =
      25) underestimated their difficulties, while ratings of those with moderate (n =
      14) and mild (n = 14) TBI were consistent with their informants, that is, in
      areas of cognition and emotion. Controls reported difficulty in interpersonal
      functioning and emotional control that their informants were unaware of.

PMID- 10079046
TI  - Identification of language-specific brain activity using magnetoencephalography.
AB  - The purpose of the present investigation was to explore the ability of
      magnetoencephalography (MEG) to identify brain areas involved in language
      comprehension. Event-related magnetic fields (ERFs) were recorded from 7 right
      handed adults with no history of neurological disorder or learning disability as
      they engaged in an auditory and a visual word-recognition task. A face
      recognition task served as control. During the later portion of the ERFs,
      activity sources from both language tasks tended to overlap in temporal and
      temporo-parietal cortices. There was a clear preponderance of such sources in the
      left compared to the right hemisphere in all participants. These findings
      demonstrate that MEG is a promising tool for identifying brain regions involved
      in the analysis of linguistic stimuli, in addition to the initial encoding of
      stimulus features.

PMID- 10079047
TI  - Poststroke depression and anxiety: different assessment methods result in
      variations in incidence and severity estimates.
AB  - Patients with right and left hemisphere stroke (RH, LH) and a control group (CG)
      were administered a structured clinical interview (SCID-R) and rating scales for
      anxiety and depression (Center for Epidemiologic Studies Depression Scale, Beck
      Anxiety Inventory, and Hamilton Depression Rating Scale). The three groups did
      not differ when compared for the mean level of distress on the rating scales or
      frequency of mood or anxiety disorder diagnosis using the SCID-R. By contrast,
      participants in the LH group were more likely to be classified as distressed
      using rating scales cutoff scores and on measures of severity when compared only
      to the RH group. The rating scales were sensitive to psychiatric disorders, but
      lacked specificity in all groups. There were significant correlations between
      scales suggesting the rating scales measure a common factor in the controls,
      while in the stroke groups associations were weaker and less likely to be
      significant. Together, these results suggest the need for caution in using rating
      scales of depression and anxiety in neurologic patients and support the notion
      that these scales are sensitive to distress rather than specific for identifying
      depressive and anxiety disorders.

PMID- 10079048
TI  - Impaired acquisition and rapid forgetting of patterned visual stimuli in
      Alzheimer's disease.
AB  - Whether or not rate of forgetting is accelerated in Alzheimer's disease (AD) is
      controversial. This study examined recognition of visual patterns in patients
      with AD and in controls at 10 min relative to a learning baseline measured after
      a 10-s delay (delayed recognition ratio, DRR). Comparable baseline performances
      were attained in the two groups by manipulating stimulus exposure times.
      Comparisons between 25 AD and 48 age-matched controls demonstrated lower DRR in
      AD when initial recognition, which was statistically worse in AD, was covariated.
      DRR was also lower in an analysis of subgroups closely matched on initial
      performance. The findings suggest that forgetting is accelerated in AD because
      multiple aspects of memory processing, including storage, are impaired.

PMID- 10079049
TI  - Order effects within the Trail Making and Stroop tests in patients with
      neurologic disorders.
AB  - Effects of order of presentation within the Trail Making and Stroop tests were
      investigated by comparing 50 consecutive patients receiving detailed
      neuropsychological assessment given the components of each test in standard order
      with 50 given them in reverse. Groups were well matched on a wide range of
      demographic and neuropsychological variables. The only significant group
      difference in mean scores for the test components and derived ratios and
      differences, a higher Trail Making Test Part B/Part A ratio in the 'reverse'
      group than in the 'standard' group, was most easily explained in terms of a
      slight effect of practice in visual scanning. Greater variance in the Stroop Test
      Part C score and its derivatives in the standard group may have been attributable
      to factors other than order of presentation. Performance of these tests in
      patients with neurological disorders is not crucially dependent upon accumulation
      of proactive interference from simpler to more complex parts; the latter can
      reasonably be used in isolation.

PMID- 10079050
TI  - Regression equations in clinical neuropsychology: an evaluation of statistical
      methods for comparing predicted and obtained scores.
AB  - Regression equations are widely used in clinical neuropsychology, particularly as
      an alternative to conventional normative data. In neuropsychological applications
      the most common method of making inferences concerning the difference between an
      individual's test score and the score predicted by a regression equation is to
      multiply the standard error of estimate by an appropriate value of z to form
      confidence limits around the predicted score. The technically correct method is
      to calculate the standard error of a new individual Y and multiply it by the
      value of t corresponding to the desired limits (e.g., 90% or 95%). These two
      methods are compared in data sets generated to be broadly representative of data
      sets used in clinical neuropsychology. The former method produces confidence
      limits which are narrower than the true confidence limits and fail to reflect the
      fact that limits become wider as scores on the predictor deviate from the mean.
      However, for many of the example data sets studied, the differences between the
      two methods were trivial, thereby providing reassurance for those who use the
      former (technically incorrect) method. Despite this, it would be preferable to
      use the correct method particularly with equations derived from samples with
      modest Ns, and for individuals with extreme scores on the predictor variable(s).
      To facilitate use of the correct method a computer program is made available for
      clinical practice.

PMID- 10079051
TI  - ATP depletion, purine riboside triphosphate accumulation and rat thymocyte death
      induced by purine riboside.
AB  - Purine riboside (purine-1-D-ribofuranoside, nebularine), an adenosine analog,
      exerts cytotoxic effect both in vivo and in vitro. However, exact biochemical
      mechanism for its toxicity and sensitivity of lymphoid cells remains unknown. The
      present experiments have examined the sequential metabolic changes leading to
      cell death, induced in cultured rat thymocytes during incubation with purine
      riboside. Among 22 analogs tested, purine-riboside and tubercidin were most toxic
      as determined by trypan blue exclusion and lactate dehydrogenase leakage from the
      cells. 2-Chloroadenosine and 2'-deoxyadenosine were only moderately toxic,
      whereas other analogs tested were without effect on cell viability. In the
      presence of purine riboside, more than 90% of ATP was lost after 2 h of
      incubation. Hypoxanthine accumulated in the medium and the formation of purine
      riboside triphosphate exceeded 4-fold the physiological concentration of ATP in
      the cell. Inhibition of adenosine kinase by 5-iodotubercidin reversed the
      cytotoxic effect of purine riboside. Interestingly, cells virtually deprived of
      ATP after 2 h of incubation with purine riboside maintained high nucleotide
      energy charge value and high viability. Purine riboside triphosphate was capable
      to replace ATP in stimulation of glycolysis in cell-free thymus extract. We
      conclude that for a short time (a few hours) purine riboside triphosphate formed
      in the cell may serve in the absence of ATP as an intermediate of cellular energy
      metabolism in rat thymocytes. However, possibly due to toxic effects of purine
      riboside triphosphate, cells were finally dying. Thus, ATP depletion and
      adenosine kinase mediated purine riboside phosphates formation are the principle
      causes of rat thymocytes death exposed to purine riboside.

PMID- 10079052
TI  - Metallothionein-I transgenic mice are not protected from gamma-radiation.
AB  - Metallothionein (MT) has been proposed to play a protective role against the
      toxic effects of free radicals and electrophiles, such as those produced by gamma
      radiation. Therefore, this study was designed to determine whether MT-transgenic
      mice, which carry 56 copies of the MT-I transgene and have higher tissue MT
      concentrations, are resistant to the toxic effects of gamma-radiation. Mice were
      exposed to 137cesium radiation, and survival was followed for 30 days. At all
      doses (7-12 Gy) examined, no difference in the survival was observed between
      control and MT-transgenic mice. The average survival times between control and MT
      transgenic mice were also similar. Leukocytes were decreased 78 +/- 7% and 75 +/-
      11% in control and MT-transgenic mice respectively 5 days after radiation.
      Furthermore, MT-transgenic mice were also equally susceptible as control mice to
      the lethal toxic effects produced by cyclophosphamide (1.75 mmol/kg, i.p.). In
      summary, MT-I transgenic mice are not protected against the toxic effects
      produced by gamma-radiation or cyclophosphamide.

PMID- 10079053
TI  - Acute pulmonary toxicity of acrolein in rats--underlying mechanism.
AB  - Acute exposure of rats to acrolein (1 or 2 ppm) resulted in reduced levels of
      glutathione, ascorbic acid and alpha-tocopherol. The activities of catalase and
      glutathione peroxidase were reduced whereas an increase in the activities of
      superoxide dismutase was observed. This led to enhanced lipid peroxidation, which
      produced extensive lung damage as indicated by the elevated levels of the
      biochemical markers--angiotensin converting enzyme, lactate dehydrogenase,
      protein and lactate in the bronchoalveolar lavage.

PMID- 10079054
TI  - Acetylaminofluorene inhibits nitric oxide production in LPS-stimulated RAW 264.7
      cells by blocking NF-kappa B/Rel activation.
AB  - The mechanism by which 2-acetylaminofluorene (AAF) inhibited nitric oxide (NO)
      formation, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was
      investigated. The decrease in NO, as demonstrated by measurement of nitrite was
      found to correlate well with a decrease in inducible nitric oxide synthase (iNOS)
      mRNA. Since the promoter in iNOS gene contains binding motifs for NF-kappa B/Rel,
      AP-1, and NF-IL6 which appear to be important for LPS-mediated iNOS induction,
      the effect of AAF on the activation of these transcription factors was
      determined. Treatment of AAF to RAW 264.7 cells induced a dose-related inhibition
      of NF-kappa B/Rel in chloramphenicol acetyltransferase activity, while either AP
      1 or NF-IL6 activation was not affected by AAF. Treatment of RAW 264.7 cells with
      AAF inhibited protein/DNA binding of NF-kappa B/Rel to its cognate site as
      measured by electrophoretic mobility shift assay. In addition, AAF treatment
      caused a significant reduction of nuclear c-rel, p65, and p50 protein levels, and
      this decrease was paralleled by the accumulation of cytoplasmic c-rel, p65, and
      p50. These data suggest that AAF inhibits iNOS gene expression by a mechanism
      involving a blockade of LPS-induced nuclear translocation of NF-kappa B/Rel.

PMID- 10079055
TI  - Elevation of micronuclei frequency in mouse bone marrow treated with various
      doses of teniposide (VM-26).
AB  - The effect of various doses (0-10 mg/kg body wt.) of teniposide (VM-26) was
      studied on the induction of micronuclei at 12, 24 and 36 h post-treatment. The
      frequency of micronuclei (MPCE and MNCE) increased in a dose-dependent manner up
      to a dose of 0.3125 mg/kg VM-26, where a peak frequency of micronuclei was
      observed. A further increase in the drug dose resulted in the reduction in
      micronuclei frequency in comparison with 0.3125 mg/kg drug dose reaching a nadir
      at 10 mg/kg. However, it was significantly higher than DDW (double distilled
      water) treated controls. The pattern of micronuclei induction was similar for all
      the post-treatment time periods. The frequency of micronuclei also increased with
      scoring time and the highest frequency of micronuclei was observed at 24 h post
      treatment, which declined thereafter without restoration to DDW treated control
      level. Conversely, the PCE/NCE ratio registered a dose-dependent decline after
      treatment of mice with various doses of VM-26. A peak decline was observed at a
      dose of 0.3125 mg/kg, thereafter the decline became consistently less resulting
      in an elevation in the PCE/NCE ratio in comparison with 0.3125 mg/kg VM-26.

PMID- 10079056
TI  - Aluminum effects upon calbindin D9k-linked duodenal calcium transport in diabetic
      male rats.
AB  - In order to elucidate if the inhibition mechanisms of Aluminum (Al) on intestinal
      calcium flux involve some possible action on calbindin-D9k, a series of in vivo
      and in vitro experiments were carried out in normal and in streptozotocin-induced
      diabetic male rats. The dose-response curves obtained from the in vitro studies
      indicate that, in the diabetic group (which has a lower content of calbindin
      D9k), the effect of Al on JCa(ms) has a small dependence on rising Al
      concentration (0-10 microM). The parameters obtained from those curves: Emax
      (maximum reduction percentage of JCa(ms)) and ED50 (Al concentration that
      produces half of the highest inhibition) were significantly diminished in this
      group compared to control. Both s.c. injections of calcitriol (D3) at doses of
      0.08 and 0.40 microg/kg body wt. per day and insulin (10 IU/kg body wt. per day),
      increase the inhibitory effect of Al to levels that did not differ from controls.
      In vivo gavage of 60 mg/kg body wt. per day of aluminum chloride for 1 week
      reveals that the degree of reduction of intestinal CaBP9k by Al is directly
      correlated to duodenal content of this protein (r2 = 0.683, P = 0.022).

PMID- 10079057
TI  - Impact of massive ascorbic acid supplementation on alcohol induced oxidative
      stress in guinea pigs.
AB  - The effects of a mega dose of ascorbic acid (AA) on alcohol induced peroxidative
      damages were investigated in guinea pigs. In the present study, four groups of
      male guinea pigs were maintained for 30 days as follows. (1) Control group (1 mg
      AA/100 g body wt); (2) Ethanol group (1 mg AA/100 g body wt. + 9 g ethanol/kg
      body wt); (3) AA group (25 mg AA/100 g body wt); (4) AA + ethanol group (25 mg
      AA/100 g body wt. + 9 g ethanol/kg). Results revealed that alcohol induced
      significant lipid peroxidation, since the lipid peroxidation products
      malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated. The
      activities of scavenging enzymes superoxide dismutase (SOD), catalase were
      reduced. However, supplementation of AA along with alcohol reduced the lipid
      peroxidation products in the liver and enhanced the activities of scavenging
      enzymes. Activities of glutathione peroxidase and reductase were also greater in
      guinea pigs given alcohol + AA in comparison with those given alcohol alone.
      Administration of ascorbic acid also reduced the activity of gamma-glutamyl
      transpeptidase (GGT), the marker enzyme of alcohol induced toxicity. The vitamin
      E level, which was reduced by alcohol intake, was raised by the co-administration
      of AA and alcohol. These studies suggest that a mega dose of AA helps in the
      prevention of alcohol induced oxidative stress by enhancing the antioxidant
      capacity and also by reducing the lipid peroxidation products.

PMID- 10079058
TI  - An acute intratracheal selenium study: immediate effects on respiration in guinea
      pigs.
AB  - Pulmonary function was assessed in non-sensitized male guinea pigs (206-445 g)
      before and after intratracheal (ITr) treatment with saline or selenium (Se, 0.06
      mg/100 g body weight) as selenium dioxide (SeO2) or seleno-L-methionine (SeM).
      Pulmonary functional parameters such as the respiratory rate (f), tidal volume
      (TV), dynamic lung compliance (Cdynl) and lung resistance (Rl) were determined
      using the respiratory flow (F) signal and the transpulmonary signal obtained via
      the intrapleural pressure (P) from the animal. Although, pulmonary dysfunction
      was observable with exposure to two different Se compounds, the SeO2-induced
      changes in f and Rl were significant (P < 0.05). Treatment with SeM did not
      result in alteration of any of the parameters significantly. Results indicated
      that acute ITr SeO2 exposure affects respiration precipitated by a significantly
      decreased f and an increased Rl unlike after SeM. The Cdynl did not change
      significantly after treatment with either of the two Se compounds. Comparing the
      immediate effects of the two different Se compounds on respiration, acute ITr
      SeO2 exposure was found to be more detrimental to pulmonary function than SeM.

PMID- 10079059
TI  - Bgugaine, a pyrrolidine alkaloid from Arisarum vulgare, is a strong hepatotoxin
      in rat and human liver cell cultures.
AB  - Toxicity of bgugaine, a pyrrolidine alkaloid extracted from the tubers of
      Arisarum vulgare, was studied in three different liver cell culture models: (1)
      the rat hepatocyte primary culture; (2) a liver epithelial cell line; and (3) the
      human hepatoblastoma cell line HepG2. Cytotoxicity was evaluated by LDH release,
      MTT reduction and MDA production. DNA fragmentation was analysed by flow
      cytometry or DNA gel-electrophoresis. In hepatocyte and epithelial cell cultures,
      drug toxicity appeared at 30 microM and was evaluated by an increase in LDH
      release, a decrease in MTT reduction and a higher level of MDA production.
      Bgugaine concentrations lower than 30 microM did not induce changes in these
      parameters. In HepG2 cells, bgugaine treatment also induced LDH release at
      concentrations of 40 and 50 microM. DNA fragmentation, analysed in the HepG2 cell
      line by flow cytometry, was observed in cultures exposed to 50 microM bgugaine.
      However, using DNA gel-electrophoresis, we demonstrated that lower bgugaine
      concentrations (10, 20 and 30 microM) also induced DNA damage. Our results show
      that: (1) bgugaine induces an important hepatotoxicity; (2) bgugaine toxicity is
      not mediated by a metabolic derivative; and (3) bgugaine induces a significant
      DNA damage. Therefore, our data suggest that the alkaloid bgugaine contained in
      Arisarum vulgarae may be involved in the toxicologic symptoms observed after
      consumption of this plant tubers by humans and animals.

PMID- 10079060
TI  - Intracellular behaviour of uranium(VI) on renal epithelial cell in culture (LLC
      PK1): influence of uranium speciation.
AB  - The main objective of this work was to assess the potentiality of in vitro models
      to study and understand the uranium-induced cytotoxicity on renal cells.
      Cytotoxicity and morphological studies were performed in a tubular proximal
      original established cell line (LLC-PK1 cell line). Dose-dependent cytotoxicity
      response was obtained with the uranium bicarbonate complex. In vitro experiments
      revealed a toxicity of uranium-bicarbonate complexes after a 24-h exposition and
      for concentrations ranging from 7 x 10(-4) M to 10(-3) M. In contrast, a lack of
      cytotoxicity of uranium(VI) citrate complexes studied using the same experimental
      conditions was noticed. Furthermore, electron transmission microscopy and X-ray
      microanalysis studies, after exposition of LLC-PK1 cells to the uranium
      bicarbonate system ([U] = 8 x 10(-4) M) revealed that uranium entered into the
      cells and it was precipitated within the cytoplasmic compartment as uranyl
      phosphate needles. Similar morphological studies conducted with citrate complexes
      did not show any intake of uranium by LLC-PK1 cells. Experiments conducted in
      phosphate free culture medium showed that uranium was incorporated as a soluble
      material and that the association of the metal with phosphate ions occurred in
      the cytoplasmic compartment of LLC-PK1 cells.

PMID- 10079061
TI  - Hemolysis associated with 25% human albumin diluted with sterile water--United
      States, 1994-1998.
AB  - Since 1994, a shortage of 5% human albumin, a product used off-label during
      therapeutic plasma exchange (TPE), has existed in the United States. Because of
      this shortage, hospital pharmacists may prepare 5% solution of human albumin by
      diluting 25% human albumin with 0.9% NaCl or, when sodium load is a concern, 5%
      dextrose. However, if sterile water alone is used as the diluent, the osmolarity
      (tonicity) of the albumin solution is reduced and may cause hemolysis in
      recipients. This report describes two of 10 episodes of hemolysis (one fatal)
      among persons who received 25% human albumin diluted with sterile water and
      emphasizes that sterile water alone should not be used to dilute albumin.

PMID- 10079062
TI  - Availability of immune globulin intravenous for treatment of immune deficient
      patients--United States, 1997-1998.
AB  - Immune globulin intravenous (IGIV) is a lifesaving treatment for patients with
      primary immunodeficiency. Since November 1997, a shortage of IGIV has existed in
      the United States. In 1998, the Food and Drug Administration (FDA) required
      pharmaceutical companies to increase the frequency of reporting on IGIV
      distribution from biannually to monthly; in addition, FDA facilitated IGIV
      distribution and informed clinicians about the ongoing shortage. To assess the
      impact of the IGIV shortage on patient care, in 1998 the Immune Deficiency
      Foundation (IDF) surveyed physicians caring for immunodeficient patients about
      whether they have had difficulty obtaining IGIV, measures they have taken because
      of the shortage, and the effect of the shortage on their patients. This report
      summarizes data reported to FDA and data obtained from the IDF survey and
      provides recommendations for IGIV use during the shortage.

PMID- 10079063
TI  - Nosocomial group A streptococcal infections associated with asymptomatic health
      care workers--Maryland and California, 1997.
AB  - Group A Streptococcus (GAS), a common cause of pharyngitis and uncomplicated skin
      and soft tissue infections, can cause serious invasive infections (including
      necrotizing fasciitis and streptococcal toxic-shock syndrome [STSS]) and death.
      Since 1965, at least 15 postoperative or postpartum GAS outbreaks attributed to
      asymptomatic carriage in health-care workers (HCWs) have been reported. This
      report describes two nosocomial outbreaks of GAS infection in Maryland and
      California during 1996-1997; the findings suggest that early infection-control
      measures that include active surveillance may interrupt transmission and prevent
      morbidity and mortality.

PMID- 10079064
TI  - Cyclization of globular DNA. Implications for DNA-DNA interactions in vivo.
AB  - The rate of cyclization of lambda DNA varies over more than 6 orders of
      magnitude, from 3.2 x 10(-7) s-1 to 2 s-1, in a Tris-EDTA buffer as a function of
      spermidine concentration. This variation is strictly correlated with the
      conformation of the chain. The highest rates are obtained when the chain is
      collapsed into a dense globular state. The effective concentration of the chain
      ends in the reaction is then 87 000-fold greater than in the random coil state.
      These results show that DNA globularity must be taken into account to understand
      biological processes involving intramolecular DNA-DNA interactions.

PMID- 10079065
TI  - Fragment reconstitution of a small protein: disulfide mutant of a short C
      terminal fragment derived from streptococcal protein G.
AB  - Hierarchical studies on the folding of protein G B1 domain have shown that the C
      terminal fragment (C16) has a considerable amount of beta-hairpin structure that
      exchanges between the folded and unfolded states at room temperature, and that
      the C16 fragment binds noncovalently to an N-terminal fragment (N40) under
      physiological conditions. Those studies have led us to the hypothesis that the
      amphipathic beta-hairpin structure of C16 initiates folding of the domain. To
      obtain a more detailed understanding of the folding mechanism of the domain, we
      designed a mutant of C16 (SS16ox) with a disulfide bond between residues 41 and
      56, and then examined the interaction of the mutant with N40 by surface plasmon
      resonance (SPR) and by thermal denaturation studies using circular dichroism.
      SS16ox strongly interacted with N40, with an equilibrium constant, KD, that was 7
      fold higher than wild-type. The association rate constant, kon, of SS16ox was 8.7
      fold higher than that of wild-type. This strong interaction can be explained by
      the entropic effect of the disulfide bond. The introduction of the disulfide bond
      into C16 stabilizes the beta-hairpin structure of C16, accelerates the
      association rate with N40, and then stabilizes the whole complex. These results
      support a hypothetical folding mechanism of protein G where the amphipathic beta
      hairpin structure of C16 acts as a nucleus and accelerates folding of the whole
      molecule.

PMID- 10079066
TI  - N-acylglycine amidation: implications for the biosynthesis of fatty acid primary
      amides.
AB  - Bifunctional peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the O2
      dependent conversion of C-terminal glycine-extended prohormones to the active, C
      terminal alpha-amidated peptide and glyoxylate. We show that alpha-AE will also
      catalyze the oxidative cleavage of N-acylglycines, from N-formylglycine to N
      arachidonoylglycine. N-Formylglycine is the smallest amide substrate yet reported
      for alpha-AE. The (V/K)app for N-acylglycine amidation varies approximately 1000
      fold, with the (V/K)app increasing as the acyl chain length increases. This
      effect is largely an effect on the KM,app; the KM,app for N-formylglycine is 23
      +/- 0.88 mM, while the KM,app for N-lauroylglycine and longer chain N
      acylglycines is in the range of 60-90 microM. For the amidation of N
      acetylglycine, N-(tert-butoxycarbonyl)glycine, N-hexanoylglycine, and N
      oleoylglycine, the rate of O2 consumption is faster than the rate of glyoxylate
      production. These results indicate that there must be the initial formation of an
      oxidized intermediate from the N-acylglycine before glyoxylate is produced. The
      intermediate is shown to be N-acyl-alpha-hydroxyglycine by two-dimensional 1H-13C
      heteronuclear multiple quantum coherence (HMQC) NMR.

PMID- 10079067
TI  - The cytosolic class II chaperonin CCT recognizes delineated hydrophobic sequences
      in its target proteins.
AB  - The nonhomologous proteins actin and alpha- and beta-tubulin need the assistance
      of the cytosolic chaperonin containing TCP-1 (CCT) to reach their correct native
      state, and their folding requires a transient binary complex formation with CCT.
      We show that separate or combined deletion of three delineated hydrophobic
      sequences in actin disturbs the interaction with CCT. These sites are situated
      between residues 125-179, 244-285, and 340-375. Also, alpha- and beta-tubulin
      contain at least one recognition region, and intriguingly, it has a similar
      distribution of hydrophobic residues as region 244-285 in actin. Internal
      deletion of the sites in actin favor a model for cooperative binding of target
      proteins to CCT. Peptide mimetics, representing the binding regions, inhibit
      target polypeptide binding to CCT, suggesting that actin and tubulin contact
      similar CCT subunits. In addition, we show that actin recognition by class II
      chaperonins is different from that by class I.

PMID- 10079068
TI  - Influence of amino acid substitutions related to inherited human prion diseases
      on the thermodynamic stability of the cellular prion protein.
AB  - Transmissible spongiform encephalopathies (TSEs) are caused by a unique
      infectious agent which appears to be identical with PrPSc, an oligomeric,
      misfolded isoform of the cellular prion protein, PrPC. All inherited forms of
      human TSEs, i.e., familial Creutzfeldt-Jakob disease, Gerstmann-Straussler
      Scheinker syndrome, and fatal familial insomnia, segregate with specific point
      mutations or insertions in the gene coding for human PrP. Here we have tested the
      hypothesis that these mutations destabilize PrPC and thus facilitate its
      conversion into PrPSc. Eight of the disease-specific amino acid replacements are
      located in the C-terminal domain of PrPC, PrP(121-231), which constitutes the
      only part of PrPC with a defined tertiary structure. Introduction of all these
      replacements into PrP(121-231) yielded variants with the same spectroscopic
      characteristics as wild-type PrP(121-231) and similar to full-length PrP(23-231),
      which excludes the possibility that the exchanges a priori induce a PrPSc-like
      conformation. The thermodynamic stabilities of the variants do not correlate with
      specific disease phenotypes. Five of the amino acid replacements destabilize
      PrP(121-231), but the other variants have the same stability as the wild-type
      protein. These data suggest that destabilization of PrPC is neither a general
      mechanism underlying the formation of PrPSc nor the basis of disease phenotypes
      in inherited human TSEs.

PMID- 10079069
TI  - Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage
      migration inhibitory factor, at 1.54 A resolution.
AB  - D-Dopachrome tautomerase shares a low homologous amino acid sequence (33%
      homology) with the macrophage migration inhibitory factor (MIF) and possesses
      similar tautomerase activity as well. MIF is a cytokine involved in inflammatory
      reactions and immune responses. Whereas recent studies have identified MIF as a
      pituitary hormone and immunoregulator, much less is known about the structural
      basis of these physiological functions and the real significance of tautomerase
      activity. Therefore, interest in the structure-function relationship between D
      dopachrome tautomerase and MIF has increased, especially with regard to
      inflammation and immune responses. We have determined the X-ray crystal structure
      of human D-dopachrome tautomerase at 1.54 A resolution. D-Dopachrome tautomerase
      folds to form a homotrimer that has extensive contact between subunits by
      intersubunit beta-sheets. Its overall topology and trimeric formations are
      similar to those of human MIF. The N-terminal proline is located at the bottom of
      a positively charged pocket in which the conformations of Lys32 and Ser63 are
      highly conserved. These positively charged properties are also seen in the active
      site pocket of human MIF, bacterial 5-(carboxymethyl)-2-hydroxymuconate isomerase
      (CHMI), and 4-oxalocrotonate tautomerase (4-OT). A detailed comparison of these
      structures revealed significant differences in the environment around the
      potential active site, the intersubunit contacts, and charge distribution on the
      molecular surface. It can be concluded that these features are related to the
      physiological role and tautomerase activity of MIF and D-dopachrome tautomerase.
      The present structural study could be helpful for designing effective inhibitors
      that modulate immunoregulatory and hormone-like effects.

PMID- 10079070
TI  - Familial prion disease mutation alters the secondary structure of recombinant
      mouse prion protein: implications for the mechanism of prion formation.
AB  - A considerable body of data supports the model that the infectious agent (called
      a prion) which causes the transmissible spongiform encephalopathies is a
      replicating polypeptide devoid of nucleic acid. Prions are believed to propagate
      by changing the conformation of the normal cellular prion protein (PrPc) into an
      infectious isoform without altering the primary sequence. Proteins equivalent to
      the mature form of the wild-type mouse prion protein (residues 23-231) or with a
      mutation equivalent to that associated with Gerstmann-Straussler-Scheinker
      disease (proline to leucine at codon 102 in human; 101 in mouse) were expressed
      in E. coli. The mutation did not alter the relative proteinase K susceptibility
      properties of the mouse prion proteins. The wild-type and mutant proteins were
      analyzed by circular dichroism under different pH and temperature conditions. The
      mutation was associated with a decrease in alpha-helical content, while the beta
      sheet content of the two proteins was unchanged. This suggests the mutation,
      while altering the secondary structure of PrP, is not sufficient to induce
      proteinase K resistance and could therefore represent an intermediate isoform
      along the pathway toward prion formation.

PMID- 10079071
TI  - Enzymatic determinants of the substrate specificity of CYP2C9: role of B'-C loop
      residues in providing the pi-stacking anchor site for warfarin binding.
AB  - Previous modeling efforts have suggested that coumarin ligand binding to CYP2C9
      is dictated by electrostatic and pi-stacking interactions with complementary
      amino acids of the protein. In this study, analysis of a combined CoMFA-homology
      model for the enzyme identified F110 and F114 as potential hydrophobic, aromatic
      active-site residues which could pi-stack with the nonmetabolized C-9 phenyl ring
      of the warfarin enantiomers. To test this hypothesis, we introduced mutations at
      key residues located in the putative loop region between the B' and C helices of
      CYP2C9. The F110L, F110Y, V113L, and F114L mutants, but not the F114Y mutant,
      expressed readily, and the purified proteins were each active in the metabolism
      of lauric acid. The V113L mutant metabolized neither (R)- nor (S)-warfarin, and
      the F114L mutant alone displayed altered metabolite profiles for the warfarin
      enantiomers. Therefore, the effect of the F110L and F114L mutants on the
      interaction of CYP2C9 with several of its substrates as well as the potent
      inhibitor sulfaphenazole was chosen for examination in further detail. For each
      substrate examined, the F110L mutant exhibited modest changes in its kinetic
      parameters and product profiles. However, the F114L mutant altered the metabolite
      ratios for the warfarin enantiomers such that significant metabolism occurred for
      the first time on the putative C-9 phenyl anchor, at the 4'-position of (R)- and
      (S)-warfarin. In addition, the Vmax for (S)-warfarin 7-hydroxylation decreased 4
      fold and the Km was increased 13-fold by the F114L mutation, whereas kinetic
      parameters for lauric acid metabolism, a substrate which cannot interact with the
      enzyme by a pi-stacking mechanism, were not markedly affected by this mutation.
      Finally, the F114L mutant effected a greater than 100-fold increase in the Ki for
      inhibition of CYP2C9 activity by sulfaphenazole. These data support a role for B'
      C helix loop residues F114 and V113 in the hydrophobic binding of warfarin to
      CYP2C9, and are consistent with pi-stacking to F114 for certain aromatic ligands.

PMID- 10079072
TI  - Structure of a Michaelis complex analogue: propionate binds in the substrate
      carboxylate site of alanine racemase.
AB  - The structure of alanine racemase from Bacillus stearothermophilus with the
      inhibitor propionate bound in the active site was determined by X-ray
      crystallography to a resolution of 1.9 A. The enzyme is a homodimer in solution
      and crystallizes with a dimer in the asymmetric unit. Both active sites contain a
      pyridoxal 5'-phosphate (PLP) molecule in aldimine linkage to Lys39 as a
      protonated Schiff base, and the pH-independence of UV-visible absorption spectra
      suggests that the protonated PLP-Lys39 Schiff base is the reactive form of the
      enzyme. The carboxylate group of propionate bound in the active site makes
      numerous interactions with active-site residues, defining the substrate binding
      site of the enzyme. The propionate-bound structure therefore approximates
      features of the Michaelis complex formed between alanine racemase and its amino
      acid substrate. The structure also provides evidence for the existence of a
      carbamate formed on the side-chain amino group of Lys129, stabilized by
      interactions with one of the residues interacting with the carboxylate group of
      propionate, Arg136. We propose that this novel interaction influences both
      substrate binding and catalysis by precisely positioning Arg136 and modulating
      its charge.

PMID- 10079073
TI  - Redox properties of flavocytochrome c3 from Shewanella frigidimarina NCIMB400.
AB  - The thermodynamic and catalytic properties of flavocytochrome c3 from Shewanella
      frigidimarina have been studied using a combination of protein film voltammetry
      and solution methods. As measured by solution kinetics, maximum catalytic
      efficiencies for fumarate reduction (kcat/Km = 2.1 x 10(7) M-1 s-1 at pH 7.2) and
      succinate oxidation (kcat/Km = 933 M-1 s-1 at pH 8.5) confirm that
      flavocytochrome c3 is a unidirectional fumarate reductase. Very similar catalytic
      properties are observed for the enzyme adsorbed to monolayer coverage at a
      pyrolytic graphite "edge" electrode, thus confirming the validity of the
      electrochemical method for providing complementary information. In the absence of
      fumarate, the adsorbed enzyme displays a complex envelope of reversible redox
      signals which can be deconvoluted to yield the contributions from each active
      site. Importantly, the envelope is dominated by the two-electron signal due to
      FAD [E degrees ' = -152 mV vs the standard hydrogen electrode (SHE) at pH 7.0 and
      24 degrees C] which enables quantitative examination of this center, the visible
      spectrum of which is otherwise masked by the intense absorption bands due to the
      hemes. The FAD behaves as a cooperative two-electron center with a pH-dependent
      reduction potential that is modulated (pKox at 6.5) by ionization of a nearby
      residue. In conjunction with the kinetic pKa values determined for the forward
      and reverse reactions (7.4 and 8.6, respectively), a mechanism for fumarate
      reduction, incorporating His365 and an anionic form of reduced FAD, is proposed.
      The reduction potentials of the four heme groups, estimated by analysis of the
      underlying envelope, are -102, -146, -196, and -238 mV versus the SHE at pH 7.0
      and 24 degrees C and are comparable to those determined by redox potentiometry.

PMID- 10079074
TI  - Multiple factors influence the binding of a soluble, Ca2+-independent,
      diacylglycerol kinase to unilamellar phosphoglyceride vesicles.
AB  - We studied the influence of membrane lipids, MgCl2, and ATP on the ability of a
      soluble diacylglycerol kinase to bind to 100-nm lipid vesicles. The enzyme did
      not bind detectably to vesicles that contained phosphatidylcholine alone or to
      vesicles that contained 50 mol % phosphatidylcholine + 50 mol %
      phosphatidylethanolamine. But it did bind to vesicles that contained anionic
      phosphoglycerides, and maximal binding occurred (in the presence of MgCl2) when
      the vesicles contained anionic phosphoglycerides alone. When increasing amounts
      of phosphatidylcholine were included in phosphatidylserine-containing vesicles,
      enzyme binding to the vesicles decreased by as much as 1000-fold. However, when
      increasing amounts of phosphatidylethanolamine were included in
      phosphatidylserine-containing vesicles, little change in binding occurred until
      the concentration of phosphatidylserine was reduced to below 25 mol %. These
      results and results obtained with vesicles that contained various mixtures of
      anionic phosphoglycerides, phosphatidylcholine, phosphatidylethanolamine, and
      unesterified cholesterol provided evidence that anionic phosphoglycerides were
      positive effectors of binding, phosphatidylcholine was a negative effector, and
      phosphatidylethanolamine and unesterified cholesterol were essentially neutral
      diluents. Other experiments showed that diacylglycerol and some of its structural
      analogues also were important, positive effectors of enzyme binding and that
      addition of ATP to the medium increased their effects. The combined results of
      the study suggest that the enzyme may bind to vesicles via at least two types of
      binding sites: one type that requires anionic phospholipids and is enhanced by
      Mg2+ but inhibited by phosphatidylcholine, and one type that requires
      diacylglycerol and is enhanced by ATP.

PMID- 10079075
TI  - Affinity purification and catalytic properties of a soluble, Ca2+-independent,
      diacylglycerol kinase.
AB  - We used a new procedure that involved selective enzyme binding to lipid vesicles
      to partially purify a soluble diacylglycerol kinase, then studied the relation
      between enzyme-vesicle binding and activity in vesicle-based assays. The vesicle
      binding procedure required about 2 h, increased the enzyme's specific activity 50
      fold with a 50% yield of activity, and combined well with additional purification
      steps. Studies of the activity of the partially purified diacylglycerol kinase
      toward vesicle-associated diacylglycerols revealed linear reaction kinetics that
      reflected enzyme binding to the vesicles; factors known to influence enzyme
      binding to the vesicles affected enzyme activity only indirectly, not by
      influencing the diacylglycerol kinase reaction itself. On the other hand, special
      incubation experiments that caused both substrate depletion in vesicles and
      enzyme stalling provided evidence that the diacylglycerol kinase could desorb
      from these vesicles, adsorb to freshly added, substrate-containing vesicles, and
      resume catalysis of phosphorylation reactions. The molecular basis for this
      enzyme-vesicle "hopping" behavior remains to be clarified. But enzyme-catalyzed
      conversion of diacylglycerol to phosphatidic acid may not have been a
      contributing factor because separate, enzyme-vesicle binding experiments showed
      that the enzyme had only a marginally higher affinity for diacylglycerol
      containing vesicles than it did for vesicles that contained comparable amounts of
      phosphatidic acid. The combined results of our experiments suggest that the
      linear rates of diacylglycerol phosphorylation observed in standard assays with
      diacylglycerol-containing vesicles may have been combined functions of both the
      rate of enzyme hopping among vesicles and the rate of diacylglycerol
      phosphorylation by enzyme that was bound transiently on substrate-containing
      vesicles.

PMID- 10079076
TI  - Kinetic mechanism of uracil phosphoribosyltransferase from Escherichia coli and
      catalytic importance of the conserved proline in the PRPP binding site.
AB  - Phosphoribosyltransferases catalyze the formation of nucleotides from a
      nitrogenous base and 5-phosphoribosyl-alpha-1-pyrophosphate (PRPP). These enzymes
      and the PRPP synthases resemble each other in a short homologous sequence of 13
      amino acid residues which has been termed the PRPP binding site and which
      interacts with the ribose 5-phosphate moiety in structurally characterized
      complexes of PRPP and nucleotides. We show that each class of
      phosphoribosyltransferases has subtle deviations from the general consensus PRPP
      binding site and that all uracil phosphoribosyltransferases (UPRTases) have a
      proline residue at a position where other phosphoribosyltransferases and the PRPP
      synthases have aspartate. To investigate the role of this unusual proline (Pro
      131 in the E. coli UPRTase) for enzyme activity, we changed the residue to an
      aspartate and purified the mutant P131D enzyme to compare its catalytic
      properties with the properties of the wild-type protein. We found that UPRTase of
      E. coli obeyed the kinetics of a sequential mechanism with the binding of PRPP
      preceding the binding of uracil. The basic kinetic constants were derived from
      initial velocity measurements, product inhibition, and ligand binding assays. The
      change of Pro 131 to Asp caused a 50-60-fold reduction of the catalytic rate
      (kcat) in both directions of the reaction and approximately a 100-fold increase
      in the KM for uracil. The KM for PRPP was strongly diminished by the mutation,
      but kcat/KM,PRPP and the dissociation constant (KD,PRPP) were nearly unaffected.
      We conclude that the proline in the PRPP binding site of UPRTase is of only
      little importance for binding of PRPP to the free enzyme, but is critical for
      binding of uracil to the enzyme-PRPP complex and for the catalytic rate.

PMID- 10079077
TI  - Excision of 5,6-dihydroxy-5,6-dihydrothymine, 5,6-dihydrothymine, and 5
      hydroxycytosine from defined sequence oligonucleotides by Escherichia coli
      endonuclease III and Fpg proteins: kinetic and mechanistic aspects.
AB  - Oligonucleotides that contain a single modified pyrimidine, i.e., thymine glycol
      (Tg), 5,6-dihydrothymine (DHT), and 5-hydroxycytosine (5-OHC) were synthesized in
      order to investigate the substrate specificity and the excision mechanism of two
      Escherichia coli repair enzymes: endonuclease III and formamidopyrimidine DNA
      glycosylase (Fpg). Three techniques of analysis were employed. A gas
      chromatography-mass spectrometry (GC-MS) assay with HPLC prepurification was used
      to quantify the release of the modified bases, while polyacrylamide gel
      electrophoresis and matrix-assisted laser-desorption ionization-mass spectrometry
      (MALDI-MS) provided insights into the mechanism of oligonucleotide cleavage.
      Values of Vm/Km constants lead to the conclusion that the substrates are
      processed by endonuclease III with the following preference: Tg >> 5-OHC > DHT.
      This confirms that Tg is an excellent substrate for endonuclease III. Fpg
      mediated cleavage of the 5-OHC-containing oligonucleotide is processed at the
      same rate than endonuclease III. Furthermore, Fpg was found to have a little but
      relevant activity on DHT-containing oligonucleotide, thus broadening the
      substrate specificity of this enzyme to a new modified pyrimidine. While 5-OHC
      containing oligonucleotides are cleaved by the two enzymes, no or a small amount
      of the modified base was found to be released, as determined by GC-MS. From these
      data it may be suggested that 5-OHC could be modified during its enzymatic
      excision. Finally, MALDI-MS analyses shed new light on the mechanism of action of
      endonuclease III: the molecular masses of the repaired fragments of 5-OHC- and
      DHT-containing oligonucleotides showed that endonuclease III cleaves the DNA
      backbone mainly through a hydrolytic process and that no beta-elimination product
      was detected.

PMID- 10079078
TI  - RNA folding and misfolding of the hammerhead ribozyme.
AB  - The hammerhead ribozyme undergoes a well-defined two-stage folding process
      induced by the sequential binding of two magnesium ions. These probably
      correspond to the formation of domain 2 (0-500 microM magnesium ions) and domain
      1 (1-20 mM magnesium ions), respectively. In this study we have used fluorescence
      resonance energy transfer (FRET) to analyze the ion-induced folding of a number
      of variants of the hammerhead ribozyme. We find that both A14G and G8U mutations
      are highly destabilizing, such that these species are essentially unfolded under
      all conditions. Thus they appear to be blocked in the first stage of the folding
      process, and using uranyl-induced photocleavage we show that the core is
      completely accessible to this probe under these conditions. Changes at G5 do not
      affect the first transition but appear to provide a blockage at the second stage
      of folding; this is true of changes in the sugar (removal of the 2'-hydroxyl
      group) and base (G5C mutation, previously studied by comparative gel
      electrophoresis). Arrest of folding at this intermediate stage leads to a pattern
      of uranyl-induced photocleavage that is changed from the wild-type, but suggests
      a structure less open than the A14G mutant. Specific photocleavage at G5 is found
      only in the wild-type sequence, suggesting that this ion-binding site is formed
      late in the folding process. In addition to folding that is blocked at selected
      stages, we have also observed misfolding. Thus the A13G mutation appears to
      result in the ion-induced formation of a novel tertiary structure.

PMID- 10079079
TI  - A binding protein to the DNase I hypersensitive site II in HLA-DR alpha gene was
      identified as NF90.
AB  - We previously observed that IFN gamma-inducible expression of the human MHC class
      II, HLA-DR alpha, gene was enhanced by treatment with 12-O-tetradecanoylphorbol
      13-acetate (TPA) only in human monocytic leukemia THP-1 cells, but not in HeLa
      cells. In the HLA-DR alpha gene, three DNase I hypersensitive sites (DHS) are
      known to be present in the promoter region (DHS-I) and first intron (DHS-II and 
      III) and are assumed to be involved in HLA-DR alpha gene regulation. In this
      study, we found a binding factor which recognized a unique palindrome sequence
      (DHS-22) in the region of the DHS II site of the HLA-DR alpha gene in THP-1 cells
      and HeLa cells. The binding activity of this factor was decreased by TPA
      treatment in THP-1 cells, but not in HeLa cells. This binding activity was also
      detectable in nuclear extracts of bovine brains. Thus, we isolated the DHS-22
      binding factor from bovine brain nuclear extracts and finally identified it as
      NF90 on the basis of molecular mass analysis of Lys-C-digested fragments and
      amino acid sequences of the two peptides of the trypsin-digested binding protein.
      The DHS-22 binding protein(s) in THP-1 cells is (are) further confirmed by
      reactivity to an antibody against NF90, and we have demonstrated that the GST
      fusion protein of NF90 interacts with DHS-22 by electrophoretic gel mobility
      shift assay (EMSA). The mRNA of NF90 was decreased by TPA treatment in THP-1
      cells but not in HeLa cells. These results suggest that the binding of NF90 to
      the DNase I hypersensitive site II of HLA-DR alpha gene seems to negatively
      regulate HLA-DR alpha gene expression.

PMID- 10079080
TI  - MerR cross-links to the alpha, beta, and sigma 70 subunits of RNA polymerase in
      the preinitiation complex at the merTPCAD promoter.
AB  - MerR, the metalloregulator of the mercury resistance (mer) operon, binds the
      operator (merO)between -10 and -35 of the merTPCAD promoter (PT) and sequesters
      RNA polymerase (RNAP) in a closed complex. MerR represses PT until Hg(II) induces
      it to underwind merO DNA and thus facilitate open complex formation. We used
      cross-linking to determine if direct contacts between MerR and RNAP also occur
      during this process. MerR cross-linked to the alpha, beta, and sigma70 subunits
      of RNAP alone, indicating stable contacts which were further stabilized upon
      forming the preinitiation complex at PT. Hg(II) did not eliminate any of the MerR
      RNAP cross-links but did increase the relative abundance of a MerR dimer
      conformer. Interference by MerR with self-cross-links among RNAP subunits and the
      formation of an electrophoretically stable association between MerR and RNAP also
      indicated MerR-RNAP interactions. This is the first evidence for stable physical
      contacts between MerR and RNAP and for a Hg(II)-induced allosteric change in MerR
      in the transcription-competent complex.

PMID- 10079081
TI  - Endogenous substrates of sphingosine-dependent kinases (SDKs) are chaperone
      proteins: heat shock proteins, glucose-regulated proteins, protein disulfide
      isomerase, and calreticulin.
AB  - Protein kinases whose activity is detectable only in the presence of sphingosine
      (Sph) or N,N'-dimethyl-Sph (DMS), but not in the presence of 15 other
      sphingolipids, phospholipids, and glycerolipids tested (Megidish, T., et al.
      (1995) Biochem. Biophys. Res. Commun. 216, 739-747), have been termed
      "sphingosine-dependent kinases" (SDKs). We showed previously that a purified SDK
      (termed "SDK1") phosphorylates a specific Ser position of adapter/chaperone
      protein 14-3-3 isoforms beta, eta, and zeta but not tau or sigma (Megidish, T.,
      et al. (1998) J. Biol. Chem. 273, 21834-45). In this study we found the
      following: (i) other SDKs with different substrate specificities are present in
      cytosolic and membrane extracts of mouse Balb/c 3T3 (A31) fibroblasts. (ii) The
      activation of these SDKs is specific to D-erythro-Sph and its N-methyl
      derivatives, the effect of L-threo-Sph or its N-methyl derivatives is minimal,
      and nonspecific cationic amphiphiles have no effect at all. An SDK separated as
      fractions "TN31-33" phosphorylated a 50 kDa substrate which was identified as
      calreticulin, as well as two endogenous substrates with molecular mass 58 and 55
      kDa, both identified as protein disulfide isomerase (PDI). This SDK, which
      specifically phosphorylates calreticulin and PDI, both molecular chaperones found
      at high levels in endoplasmic reticulum, is tentatively termed "SDK2". Another
      SDK activity was copurified with glucose-regulated protein (GRP) and heat shock
      proteins (HSP). One GRP substrate had the same amino acid sequence as GRP94
      (synonym: endoplasmin); another HSP substrate had the same amino acid sequence as
      mouse HSP86 or HSP84, the analogues of human HSP90. An SDK activity separated and
      present in "fraction 42" from Q-Sepharose chromatography specifically
      phosphorylated GRP105 (or GRP94) and HSP68 but did not phosphorylate PDI or 14-3
      3. This SDK is clearly different from other SDKs in its substrate specificity and
      is tentatively termed "SDK3". Interestingly, substrates of all these SDKs so far
      identified are molecular chaperones or adapters capable of binding to enzymes and
      key molecules involved in signal transduction, maintaining tertiary structure of
      bioactive molecules, or maintaining cellular homeostasis in response to
      environmental stress. Thus, the essential role of Sph and DMS is to activate
      molecular chaperones, thereby providing a link to the mechanism by which SDK
      activity regulates cellular homeostasis and signal transduction.

PMID- 10079082
TI  - H-bonding maintains the active site of type 1 copper proteins: site-directed
      mutagenesis of Asn38 in poplar plastocyanin.
AB  - Type I Cu proteins maintain a trigonal N2S coordination group (with weak axial
      ligation) in both oxidation states of the Cu2+/+ ion, thereby reducing the
      reorganization energy for electron transfer. Requirements for maintaining this
      coordination group were investigated in poplar plastocyanin (Pcy) by mutation of
      a conserved element of the type 1 architecture, an asparagine residue (Asn38)
      adjacent to one of the ligating histidines. The side chain of this asparagine
      forms an active site clasp via two H-bonds with the residue (Ser85) adjacent to
      the ligating cysteine (Cys84). In addition, the main chain NH of Asn38 donates an
      H-bond to the thiolate ligand. We have investigated the importance of these
      interactions by mutating Asn38 to Gln, Thr, and Leu. The mutant proteins are
      capable of folding and binding Cu2+, but the blue color fades; the rate of fading
      increases in the order Gln < Thr < Leu. The color is not restored by
      ferricyanide, showing that the protein is modified irreversibly, probably by
      oxidation of Cys84. The more stable mutants N38Q and N38T were characterized
      spectroscopically. The wild-type properties are slightly perturbed for N38Q, but
      N38T shows remarkable similarity to another type 1 Cu protein, azurin (Azu) from
      Pseudomonas aeruginosa. The Cu-S(Cys) bond is longer in Azu than in Pcy, and the
      NH H-bond to the ligating S atom is shorter. Molecular modeling suggests a
      similar effect for N38T because the threonine residue shifts toward Ser85 in
      order to avoid a steric clash and to optimize H-bonding. These results
      demonstrate that H-bonding adjacent to the type 1 site stabilizes an architecture
      which both modulates the electronic properties of the Cu, and suppresses side
      reactions of the cysteine ligand.

PMID- 10079083
TI  - Comparison of the reaction progress of calcineurin with Mn2+ and Mg2+.
AB  - Activation of calcineurin by Mn2+ and Mg2+ was compared using a heavy atom
      isotope analogue of the substrate p-nitrophenyl phosphate (pNPP). Heavy atom
      isotope effects were measured for Mg2+ activation and compared to published
      results of the isotope effects with Mn2+ as the activating metal. Isotope effects
      were measured for the kinetic parameter Vmax/Km at the nonbridging oxygen atoms
      [18(V/K)nonbridge]; at the position of bond cleavage in the bridging oxygen atom
      [18(V/K)bridge]; and at the nitrogen atom in the nitrophenol leaving group
      [15(V/K)]. The isotope effects increased in magnitude upon changing from an
      optimal pH to a nonoptimal pH; the 18(V/K)bridge effect increased from 1.0154 (+/
      0.0007) to 1.0198 (+/-0.0002), and the 15(V/K) effect increased from 1.0018 (+/
      0. 0002) to 1.0021 (+/-0.0003). The value for 18(V/K)nonbridge is 0. 9910 (+/
      0.0003) at pH 7.0. As with Mn2+, the 18(V/K)nonbridge isotope effect indicated
      that the dianion was the substrate for catalysis, and that a dissociative
      transition state was operative for the phosphoryl transfer. Comparison to results
      for Mn2+ activation suggested that chemistry was more rate-limiting with Mg2+
      than with Mn2+. Changing the activating metal concentration showed opposite
      trends with increasing Mg2+ increasing the commitment factor and seemingly making
      the chemistry less rate-limiting. The influence of viscosity was evaluated as
      well to gauge the role of chemistry. The activation of calcineurin-catalyzed
      hydrolysis of pNPP1 by Mg2+ or Mn2+ at pH 7.0 was compared in the presence of
      viscogens, glycerol and poly(ethylene glycol). Increasing glycerol caused
      different effects with the two activators. With Mn2+ as the activator,
      calcineurin activity showed a normal response with kcat and kcat/Km decreasing
      with viscosity. There was an inverse response with Mg2+ as the activator as
      values of kcat/Km increased with viscosity. From values of the normalized kcat/Km
      with Mn2+, the chemistry was found to be partially rate-limiting, consistent with
      previous heavy atom isotope studies (22). The effect observed for Mg2+ seems
      consistent with a change in the rate-limiting step for the two different metals
      at pH 7.0.

PMID- 10079084
TI  - Mutations at four active site residues of biotin carboxylase abolish substrate
      induced synergism by biotin.
AB  - Acetyl-CoA carboxylase catalyzes the first committed step in the biosynthesis of
      long-chain fatty acids. The Escherichia coli form of the enzyme consists of a
      biotin carboxylase protein, a biotin carboxyl carrier protein, and a
      carboxyltransferase protein. In this report a system for site-directed
      mutagenesis of the biotin carboxylase component is described. The wild-type copy
      of the enzyme, derived from the chromosomal gene, is separated from the mutant
      form of the enzyme which is coded on a plasmid. Separation of the two forms is
      accomplished using a histidine-tag attached to the amino terminus of the mutant
      form of the enzyme and nickel affinity chromatography. This system was used to
      mutate four active site residues, E211, E288, N290, and R292, to alanine followed
      by their characterization with respect to several different reactions catalyzed
      by biotin carboxylase. In comparison to wild-type biotin carboxylase, all four
      mutant enzymes gave very similar results in all the different assays, suggesting
      that the mutated residues have a common function. The mutations did not affect
      the bicarbonate-dependent ATPase reaction. In contrast, the mutations decreased
      the maximal velocity of the biotin-dependent ATPase reaction 1000-fold but did
      not affect the Km for biotin. The activity of the ATP synthesis reaction
      catalyzed by biotin carboxylase where carbamoyl phosphate reacts with ADP was
      decreased 100-fold by the mutations. The ATP synthesis reaction required biotin
      to stimulate the activity in the wild-type; however, biotin did not stimulate the
      activity of the mutant enzymes. The results showed that the mutations have
      abolished the ability of biotin to increase the activity of the enzyme. Thus,
      E211, E288, N290, and R292 were responsible, at least in part, for the substrate
      induced synergism by biotin in biotin carboxylase.

PMID- 10079085
TI  - Modification of the lipid-protein interaction in human low-density lipoprotein
      destabilizes ApoB-100 and decreases oxidizability.
AB  - The interactions of the lipid and protein moiety of human low-density lipoprotein
      (LDL) and their influence on the oxidation behavior of LDL were modified using an
      amphipathic peptide, melittin, as a probe. The interaction of melittin with the
      LDL phospholipid surface resulted in a destabilization of apolipoprotein B-100
      (apoB-100) as monitored by differential scanning calorimetry, while the
      characteristics of lipid core melting remained nearly unchanged. Binding of
      melittin caused a restriction of lipid chain mobility near the glycerol backbone,
      but not in the middle or near the methyl terminus of the fatty acyl chains as
      observed by electron paramagnetic resonance. Also, upon melittin addition, the
      level of copper binding to apoB-100 and the oxidizability of LDL by Cu2+ ions
      were greatly reduced, as indicated by abolished tryptophan fluorescence quenching
      upon Cu2+ binding and, during oxidation, prolongation of the lag phase of
      oxidation, attenuated consumption of alpha-tocopherol, and a lowered maximal rate
      of conjugated diene formation. This reduction of oxidizability could not be
      reversed by increasing the Cu2+ concentration. It is deduced that interaction of
      Cu2+ and alpha-tocopherol is required for reductive activation of the metal. It
      can be abolished by interfering with the interactions between apoB-100 and the
      lipid moiety of LDL which modifies the conformation of LDL and, as a consequence,
      hinders copper binding to apoB-100.

PMID- 10079086
TI  - A functional chimera of mammalian guanylyl and adenylyl cyclases.
AB  - Adenylyl and guanylyl cyclases synthesize second messenger molecules by
      intramolecular esterification of purine nucleotides, i.e., cAMP from ATP and cGMP
      from GTP, respectively. Despite their sequence homology, both families of
      mammalian cyclases show remarkably different regulatory patterns. In an attempt
      to define the functional domains in adenylyl cyclase responsible for their
      isotypic-common activation by Galphas or forskolin, dimeric chimeras were
      constructed from soluble guanylyl cyclase alpha1 subunit and the C-terminal
      halves of adenylyl cyclases type I, II, or V. The cyclase-hybrid generated cAMP
      and was inhibited by P-site ligands. The data establish structural equivalence
      and the ability of functional complement at the catalytic sites in both cyclases.
      Detailed enzymatic characterization of the chimeric cyclase revealed a crucial
      role of the N-terminal adenylyl cyclase half for stimulatory actions, and a major
      importance of the C-terminal part for nucleotide specificity.

PMID- 10079087
TI  - Mapping the integrin alpha V beta 3-ligand interface by photoaffinity cross
      linking.
AB  - Integrins are cell surface adhesion molecules involved in mediating cell
      extracellular matrix interactions. High-resolution structural data are not
      available for these heterodimeric receptors. Previous cross-linking studies of
      integrins aimed at elucidating the nature of the receptor-ligand interface have
      been limited to identification of relatively large binding domains. To create
      reagents for "photoaffinity scanning" of the RGD-binding site of human integrin
      alpha V beta 3, new conformationally constrained ligands were designed. These
      photoreactive ligands are based on cyclo Ac-[Cys-Asn-Dmt-Arg-Gly-Asp-Cys]-OH,
      which displays an affinity of 50 nM for alpha V beta 3. This molecular scaffold
      was modified at the C-terminus by a benzophenone-containing amino acid residue, L
      4-benzoylphenylalanine (Bpa). At the N-terminus, a molecular tag was introduced
      in the form of radioactive iodine or biotin. The newly designed tagged
      photoreactive RGD-containing ligands display an affinity of 0.5-0.7 microM for
      alpha V beta 3, and cross-link efficiently and specifically to the receptor. A
      100 kDa band corresponding to the beta 3 subunit-ligand conjugate was detected as
      the major cross-linking product. Cross-linking was dependent upon the presence of
      Ca2+ and Mg2+ ions, and was competitively inhibited by a nonphotoreactive ligand.
      Enzymatic and chemical digestions of the radiolabeled photoconjugate enabled
      identification of a 20-amino acid fragment between positions 99 and 118 in the
      beta 3 chain of the integrin as the contact domain for ligand at a site adjacent
      to the C-terminal portion of the RGD triad.

PMID- 10079088
TI  - Curvature of dinucleotide poised for formation of trinucleotide in transcription
      with Escherichia coli RNA polymerase.
AB  - A frequently used schematic model of transcriptional elongation shows an RNA
      polymerase molecule moving along a linear DNA. This model is of course highly
      idealized and not compatible with promoter sequences [Gralla, J. D. (1991) Cell
      66, 415-418; Schleif, R. (1992) Annu. Rev. Biochem. 61, 199-223] and regulatory
      proteins [Koleske, A. J., and Young, R. A. (1995) Trends Biochem. Sci. 20, 113
      116; Dunaway, M., and Droge, P. (1989) Nature 341, 657-659; Muller, H. P., Sogo,
      J. M., and Schaffner, W. (1989) Cell 58, 767-777] located some distance away from
      the point of transcription initiation [Karsten, R., von Hippel, P. H., and
      Langowski, J. (1995) Trends Biochem. Sci. 20, 500-506]. These circumstances lead
      to the expectation of curvature along the DNA strand and require looping between
      sometimes distant points. We have now shown curvature in a dinucleotide formed at
      the very onset of transcription when it is poised for reaction with a
      mononucleotide to form a trinucleotide. The curvature became evident from the
      demonstration that a metal ion bound with a mononucleotide in the i+1
      (elongation) site is approximately equidistant from bases at the 5' end (i-1
      site) and 3' end (i site) of the dinucleotide. Similar results were obtained with
      three different dinucleotides and four mononucleotides. Curvature of the RNA
      initiate may reflect curvature of the DNA to which it is bound. These studies
      show curvature to be a significant feature in the interaction between DNA
      template and RNA elongate even at the very beginning of transcription.

PMID- 10079089
TI  - Optimizing the substrate specificity of a group I intron ribozyme.
AB  - Group I ribozymes can repair mutant RNAs via trans-splicing. Unfortunately,
      substrate specificity is quite low for the trans-splicing reaction catalyzed by
      the group I ribozyme from Tetrahymenathermophila. We have used a systematic
      approach based on biochemical knowledge of the function of the Tetrahymena
      ribozyme to optimize its ability to discriminate against nonspecific substrates
      in vitro. Ribozyme derivatives that combine a mutation which indirectly slows
      down the rate of the chemical cleavage step by weakening guanosine binding with
      additional mutations that weaken substrate binding have greatly enhanced
      specificity with short oligonucleotide substrates and an mRNA fragment derived
      from the p53 gene. Moreover, compared to the wild-type ribozyme, reaction of a
      more specific ribozyme with targeted substrates is much less sensitive to the
      presence of nonspecific RNA competitors. These results demonstrate how a detailed
      understanding of the biochemistry of a catalytic RNA can facilitate the design of
      customized ribozymes with improved properties for therapeutic applications.

PMID- 10079090
TI  - HlyC, the internal protein acyltransferase that activates hemolysin toxin: role
      of conserved histidine, serine, and cysteine residues in enzymatic activity as
      probed by chemical modification and site-directed mutagenesis.
AB  - HlyC is an internal protein acyltransferase that activates hemolysin, a toxic
      protein produced by pathogenic Escherichia coli. Acyl-acyl carrier protein (ACP)
      is the essential acyl donor. Separately subcloned, expressed, and purified
      prohemolysin A (proHlyA), HlyC, and [1-14C]myristoyl-ACP have been used to study
      the conversion of proHlyA to HlyA [Trent, M. S., Worsham, L. M., and Ernst
      Fonberg, M. L. (1998) Biochemistry 37, 4644-4655]. HlyC and hemolysin belong to a
      family of at least 13 toxins produced by Gram-negative bacteria. The homologous
      acyltransferases of the family show a number of conserved residues that are
      possible candidates for participation in acyl transfer. Specific chemical
      reagents and site-directed mutagenesis showed that neither the single conserved
      cysteine nor the three conserved serine residues were required for enzyme
      activity. Treatment with the reversible histidine-modifying diethyl pyrocarbonate
      (DEPC) inhibited acyltransferase activity, and acyltransferase activity was
      restored following hydroxylamine treatment. The substrate myristoyl-ACP protected
      HlyC from DEPC inhibition. These findings and spectral absorbance changes
      suggested that histidine, particularly a histidine proximal to the substrate
      binding site, was essential for enzyme activity. Site-directed mutageneses of the
      single conserved histidine residue, His23, to alanine, cysteine, or serine
      resulted in each instance in complete inactivation of the enzyme.

PMID- 10079091
TI  - Ubiquinone binding capacity of the Rhodobacter capsulatus cytochrome bc1 complex:
      effect of diphenylamine, a weak binding QO site inhibitor.
AB  - Diphenylamine (DPA), a known inhibitor of polyene and isoprene biosynthesis, is
      shown to inhibit flash-activatable electron transfer in photosynthetic membranes
      of Rhodobacter capsulatus. DPA is specific to the QO site of
      ubihydroquinone:cytochrome c oxidoreductase, where it inhibits not only reduction
      of the [2Fe-2S]2+ cluster in the FeS subunit and subsequent cytochrome c
      reduction but also heme bL reduction in the cytochrome b subunit. In both cases,
      the kinetic inhibition constant (Ki) is 25 +/- 10 microM. A novel aspect of the
      mode of action of DPA is that complete inhibition is established without
      disturbing the interaction between the reduced [2Fe-2S]+ cluster and the QO site
      ubiquinone complement, as observed from the electron paramagnetic resonance (EPR)
      spectral line shape of the reduced [2Fe-2S] cluster, which remained
      characteristic of two ubiquinones being present. These observations imply that
      DPA is behaving as a noncompetitive inhibitor of the QO site. Nevertheless, at
      higher concentrations (>10 mM), DPA can interfere with the QO site ubiquinone
      occupancy, leading to a [2Fe-2S] cluster EPR spectrum characteristic of the
      presence of only one ubiquinone in the QO site. Evidently, DPA can displace the
      more weakly bound of the two ubiquinones in the site, but this is not requisite
      for its inhibiting action.

PMID- 10079092
TI  - Regulation of Gi by the CB1 cannabinoid receptor C-terminal juxtamembrane region:
      structural requirements determined by peptide analysis.
AB  - A CB1 cannabinoid receptor peptide fragment from the C-terminal juxtamembrane
      region autonomously inhibits adenylyl cyclase activity in a neuroblastoma
      membrane preparation. The cannabinoid receptor antagonist, SR141716A, failed to
      block the response. The peptide was able to evoke the response in membranes from
      Chinese hamster ovary (CHO) cells that do not express the CB1 receptor. These
      studies are consistent with a direct activation of Gi by the peptide. To test the
      importance of a BXBXXB sequence, Lys403 was acetylated, resulting in a peptide
      having similar affinity but reduced efficacy. N-Terminal truncation of Arg401
      resulted in a 6-fold loss of affinity, which was not further reduced by
      sequential truncation of up to the first seven amino acids, four of which are
      charged. N-Terminal-truncated peptides exhibited maximal activity, suggesting
      that Gi activation can be conferred by the remaining amino acids. Truncation of
      the C-terminal Glu417 or substitution of Glu417 by a Leu or of Arg401 by a
      Norleucine reduced activity at 100 microM. The C-terminal juxtamembrane peptide
      was constrained to a loop peptide by placement of Cys residues at both terminals
      and disulfide coupling. This modification reduced the affinity 3-fold but yielded
      near-maximal efficacy. Blocking the Cys termini resulted in a loss of efficacy.
      Circular dichroism spectropolarimetry revealed that all C-terminal juxtamembrane
      peptide analogues exist in a random coil conformation in an aqueous environment.
      A hydrophobic environment (trifluoroethanol) failed to induce alpha-helix
      formation in the C-terminal juxtamembrane peptide but did so in less active
      peptides. The anionic detergent sodium dodecyl sulfate induced alpha-helix
      formation in all analogues except the loop peptide, where it induces a left
      handed PII conformation. It is concluded that alpha-helix formation is not
      required for Gi activation.

PMID- 10079093
TI  - Molecular basis for p38 protein kinase inhibitor specificity 

PMID- 10079094
TI  - Nutritional regulation of gastrointestinal growth.
AB  - Nutrition can control gastrointestinal (GI) tract growth at many stages of
      development. Fetal growth of the GI tract can be inhibited by restriction of the
      maternal diet, decrease of blood supply to the placenta, or partial obstruction
      of amniotic fluid swallowing. In most species there is an immature appearance of
      the GI mucosa that is characterized by large, long villi extending into the
      proximal colon. This pattern usually changes around the time of weaning and can
      be modified by manipulation of the diet. While total nutrition has a profound
      effect on GI development, there are specific nutrients that influence the
      epithelium during adult life. In the small intestine, glutamine has the most
      important effects and this amino acid is now considered conditionally essential.
      In the colon, dietary fiber has the strongest influence on mucosal structure and
      turnover. While it has been assumed that concentrations of bile acids and/or
      short chain fatty acids are the mediating factors, there is substantial evidence
      that mitigates against this conclusion. A better understanding of the molecular
      changes accompanying alterations in GI growth may lead to more comprehensive
      strategies for improving intestinal function and decreasing the risk of colon
      cancer.

PMID- 10079095
TI  - Organization of kinases, phosphatases, and receptor signaling complexes.

PMID- 10079096
TI  - PDZ domains: fundamental building blocks in the organization of protein complexes
      at the plasma membrane.

PMID- 10079097
TI  - MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that
      overexpress human apolipoprotein B.
AB  - The earliest recognizable atherosclerotic lesions are fatty streaks composed of
      lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of
      these foam cells, but the molecular mechanisms that govern macrophage trafficking
      through the vessel wall are poorly understood. Monocyte chemoattractant protein-1
      (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent
      monocyte agonist that is upregulated by oxidized lipids. Recent studies in
      hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor
      have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic
      lesions. To determine if MCP-1 is critically involved in atherogenesis in the
      setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1
      gene in transgenic mice expressing human apo B. Here we report that the absence
      of MCP-1 provides dramatic protection from macrophage recruitment and
      atherosclerotic lesion formation in apo B transgenic mice, without altering
      lipoprotein metabolism. Taken together with the results of earlier studies, these
      data provide compelling evidence that MCP-1 plays a critical role in the
      initiation of atherosclerosis.

PMID- 10079098
TI  - Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion,
      subepithelial fibrosis, physiologic abnormalities, and eotaxin production.
AB  - Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by
      activated CD4(+) Th2 lymphocytes. To define further its potential in vivo
      effector functions, the Clara cell 10-kDa protein promoter was used to express IL
      13 selectively in the lung, and the phenotype of the resulting transgenic mice
      was characterized. In contrast to transgene-negative littermates, the lungs of
      transgene-positive mice contained an inflammatory response around small and large
      airways and in the surrounding parenchyma. It was mononuclear in nature and
      contained significant numbers of eosinophils and enlarged and occasionally
      multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell
      metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of
      Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also
      prominently noted. Eotaxin protein and mRNA were also present in large quantities
      in the lungs of the transgene-positive, but not the transgene-negative, mice. IL
      4, IL-5, granulocyte-macrophage colony-stimulating factor, and monocyte
      chemoattractant protein-5 were not similarly detected. Physiological evaluations
      revealed significant increases in baseline airways resistance and airways
      hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus,
      the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic
      inflammatory response, mucus cell metaplasia, the deposition of Charcot-Leyden
      like crystals, airway fibrosis, eotaxin production, airways obstruction, and
      nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar
      responses in asthma or other Th2-polarized tissue responses.

PMID- 10079099
TI  - Agonist-stimulated cytoskeletal reorganization and signal transduction at focal
      adhesions in vascular smooth muscle cells require c-Src.
AB  - Thrombin and angiotensin II (angII) have trophic properties as mediators of
      vascular remodeling. Focal adhesions and actin cytoskeleton are involved in cell
      growth, shape, and movement and may be important in vascular remodeling. To
      characterize mechanisms by which thrombin and angII modulate vessel structure, we
      studied the effects of these G protein-coupled receptor ligands on focal
      adhesions in vascular smooth muscle cells (VSMCs). Both thrombin and angII
      stimulated bundling of actin filaments to form stress fibers, assembly of focal
      adhesions, and protein tyrosine phosphorylation at focal adhesions, such as
      p130Cas, paxillin, and tensin. To test whether c-Src plays a critical role in
      focal adhesion rearrangement, we analyzed cells with altered c-Src activity by
      retroviral transduction of wild-type (WT) and kinase-inactive (KI) c-Src into rat
      VSMCs, and by use of VSMCs from WT (src+/+) and Src-deficient (src-/-) mice.
      Tyrosine phosphorylation of Cas, paxillin, and tensin were markedly decreased in
      VSMCs expressing KI-Src and in src-/- VSMCs. Expression of KI-Src did not inhibit
      stress fiber formation by thrombin. Surprisingly, actin bundling was markedly
      decreased in VSMCs from src-/- mice both basally and after thrombin stimulation,
      compared with src+/+ mice. We also studied the effect of KI-Src and WT-Src on
      VSMC spreading. Expression of KI-Src reduced the rate of VSMC spreading on
      collagen, whereas WT-Src enhanced cell spreading. In conclusion, c-Src plays a
      critical role in agonist-stimulated cytoskeletal reorganization and signal
      transduction at focal adhesions in VSMCs. c-Src kinase activity is required for
      the cytoskeletal turnover that occurs in cell spreading, whereas c-Src appears to
      regulate actin bundling via a kinase-independent mechanism.

PMID- 10079100
TI  - A vascular bed-specific pathway.
AB  - The endothelial nitric oxide synthase (eNOS) gene is induced by a variety of
      extracellular signals under both in vitro and in vivo conditions. To gain insight
      into the mechanisms underlying environmental regulation of eNos expression,
      transgenic mice were generated with the 1,600-bp 5' flanking region of the human
      eNos promoter coupled to the coding region of the LacZ gene. In multiple
      independent lines of mice, transgene expression was detected within the
      endothelium of the brain, heart, skeletal muscle, and aorta. beta-galactosidase
      activity was consistently absent in the vascular beds of the liver, kidney, and
      spleen. In stable transfection assays of murine endothelial progenitor cells, the
      1,600-bp promoter region was selectively induced by conditioned media from
      cardiac myocytes, skeletal myocytes, and brain astrocytes. Cardiac myocyte
      mediated induction was partly abrogated by neutralizing anti-platelet-derived
      growth factor (PDGF) antibodies. In addition, promoter activity was upregulated
      by PDGF-AB. Analysis of promoter deletions revealed that a PDGF response element
      lies between -744 and -1,600 relative to the start site of transcription, whereas
      a PDGF-independent cardiac myocyte response element is present within the first
      166 bp of the 5' flanking region. Taken together, these results suggest that the
      eNos gene is regulated in the cardiac endothelium by both a PDGF-dependent and
      PDGF-independent microvascular bed-specific signaling pathway.

PMID- 10079101
TI  - Expression of specific chemokines and chemokine receptors in the central nervous
      system of multiple sclerosis patients.
AB  - Chemokines direct tissue invasion by specific leukocyte populations. Thus,
      chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in
      which the central nervous system (CNS) inflammatory reaction is largely
      restricted to mononuclear phagocytes and T cells. We asked whether specific
      chemokines were expressed in the CNS during acute demyelinating events by
      analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS
      extracellular space. During MS attacks, we found elevated CSF levels of three
      chemokines that act toward T cells and mononuclear phagocytes: interferon-gamma
      inducible protein of 10 kDa (IP-10); monokine induced by interferon-gamma (Mig);
      and regulated on activation, normal T-cell expressed and secreted (RANTES). We
      then investigated whether specific chemokine receptors were expressed by
      infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP
      10/Mig receptor, was expressed on lymphocytic cells in virtually every
      perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES
      receptor, was detected on lymphocytic cells, macrophages, and microglia in
      actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T
      cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results
      imply pathogenic roles for specific chemokine-chemokine receptor interactions in
      MS and suggest new molecular targets for therapeutic intervention.

PMID- 10079102
TI  - Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type
      1 and severe type 2 gaucher disease.
AB  - Gaucher disease is an autosomal recessive inborn error of glycosphingolipid
      metabolism caused by the deficient activity of the lysosomal hydrolase, acid beta
      glucosidase. Three phenotypically distinct subtypes result from different acid
      beta-glucosidase mutations encoding enzymes with absent or low activity. A severe
      neonatal type 2 variant who presented with collodion skin, ichthyosis, and a
      rapid neurodegenerative course had two novel acid beta-glucosidase alleles: a
      complex, maternally derived allele, E326K+L444P, and a paternally inherited
      nonsense mutation, E233X. Because the only other non-pseudogene-derived complex
      allele, D140H+E326K, also had the E326K lesion and was reported in a mild type 1
      patient with a D140H+E326K/K157Q genotype, these complex alleles and their
      individual mutations were expressed and characterized. Because the E233X mutation
      expressed no activity and the K157Q allele had approximately 1% normal specific
      activity based on cross-reacting immunologic material (CRIM SA) in the
      baculovirus system, the residual activity in both patients was primarily from
      their complex alleles. In the type 1 patient, the D140H+E326K allele was
      neuroprotective, encoding an enzyme with a catalytic efficiency similar to that
      of the N370S enzyme. In contrast, the E326K+L444P allele did not have sufficient
      activity to protect against the neurologic manifestations and, in combination
      with the inactive E233X lesion, resulted in the severe neonatal type 2 variant.
      Thus, characterization of these novel genotypes with non-pseudogene-derived
      complex mutations provided the pathogenic basis for their diverse phenotypes.

PMID- 10079104
TI  - Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations
      of N-region insertions during V(D)J recombination.
AB  - Template-independent nucleotide additions (N regions) generated at sites of V(D)J
      recombination by terminal deoxynucleotidyl transferase (TdT) increase the
      diversity of antigen receptors. Two inborn errors of purine metabolism,
      deficiencies of adenosine deaminase (ADA) and purine nucleoside phosphorylase
      (PNP), result in defective lymphoid development and aberrant pools of 2'
      deoxynucleotides that are substrates for TdT in lymphoid precursors. We have
      asked whether selective increases in dATP or dGTP pools result in altered N
      regions in an extrachromosomal substrate transfected into T-cell or pre-B-cell
      lines. Exposure of the transfected cells to 2'-deoxyadenosine and an ADA
      inhibitor increased the dATP pool and resulted in a marked increase in A-T
      insertions at recombination junctions, with an overall decreased frequency of
      V(D)J recombination. Sequence analysis of VH-DH-JH junctions from the IgM locus
      in B-cell lines from ADA-deficient patients demonstrated an increase in A-T
      insertions equivalent to that found in the transfected cells. In contrast,
      elevation of dGTP pools, as would occur in PNP deficiency, did not alter the
      already rich G-C content of N regions. We conclude that the frequency of V(D)J
      recombination and the composition of N-insertions are influenced by increases in
      dATP levels, potentially leading to alterations in antigen receptors and aberrant
      lymphoid development. Alterations in N-region insertions may contribute to the B
      cell dysfunction associated with ADA deficiency.

PMID- 10079103
TI  - A functional granulocyte colony-stimulating factor receptor is required for
      normal chemoattractant-induced neutrophil activation.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor
      that is widely used to treat neutropenia. In addition to stimulating
      polymorphonuclear neutrophil (PMN) production, G-CSF may have significant effects
      on PMN function. Because G-CSF receptor (G-CSFR)-deficient mice do not have the
      expected neutrophilia after administration of human interleukin-8 (IL-8), we
      examined the effect of the loss of G-CSFR on IL-8-stimulated PMN function.
      Compared with wild-type PMNs, PMNs isolated from G-CSFR-deficient mice
      demonstrated markedly decreased chemotaxis to IL-8. PMN emigration into the skin
      of G-CSFR-deficient mice in response to IL-8 was also impaired. Significant
      chemotaxis defects were also seen in response to N-formyl-methionyl-leucyl
      phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2. The
      defective chemotactic response to IL-8 does not appear to be due to impaired
      chemoattractant receptor function, as the number of IL-8 receptors and
      chemoattractant-induced calcium influx, actin polymerization, and release of
      gelatinase B were comparable to those of wild-type PMNs. Chemoattractant-induced
      adhesion of G-CSFR-deficient PMNs was significantly impaired, suggesting a defect
      in beta2-integrin activation. Collectively, these data demonstrate that selective
      defects in PMN activation are present in G-CSFR-deficient mice and indicate that
      G-CSF plays an important role in regulating PMN chemokine responsiveness.

PMID- 10079105
TI  - Neurotensin is a proinflammatory neuropeptide in colonic inflammation.
AB  - The neuropeptide neurotensin mediates several intestinal functions, including
      chloride secretion, motility, and cellular growth. However, whether this peptide
      participates in intestinal inflammation is not known. Toxin A, an enterotoxin
      from Clostridium difficile, mediates pseudomembranous colitis in humans. In
      animal models, toxin A causes an acute inflammatory response characterized by
      activation of sensory neurons and intestinal nerves and immune cells of the
      lamina propria. Here we show that neurotensin and its receptor are elevated in
      the rat colonic mucosa following toxin A administration. Pretreatment of rats
      with the neurotensin receptor antagonist SR-48, 692 inhibits toxin A-induced
      changes in colonic secretion, mucosal permeability, and histologic damage.
      Exposure of colonic explants to toxin A or neurotensin causes mast cell
      degranulation, which is inhibited by SR-48,692. Because substance P was
      previously shown to mediate mast cell activation, we examined whether substance P
      is involved in neurotensin-induced mast cell degranulation. Our results show that
      neurotensin-induced mast cell degranulation in colonic explants is inhibited by
      the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that
      colonic mast activation in response to neurotensin involves release of substance
      P. We conclude that neurotensin plays a key role in the pathogenesis of C.
      difficile-induced colonic inflammation and mast cell activation.

PMID- 10079106
TI  - Selective activation and functional significance of p38alpha mitogen-activated
      protein kinase in lipopolysaccharide-stimulated neutrophils.
AB  - Activation of leukocytes by proinflammatory stimuli selectively initiates
      intracellular signal transduction via sequential phosphorylation of kinases.
      Lipopolysaccharide (LPS) stimulation of human neutrophils is known to result in
      activation of p38 mitogen-activated protein kinase (MAPk); however, the upstream
      activator(s) of p38 MAPk is unknown, and consequences of p38 MAPk activation
      remain largely undefined. We investigated the MAPk kinase (MKK) that activates
      p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of
      this pathway, and the functional responses affected by p38 MAPk activation.
      Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only
      MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. Of
      p38 MAPk isoforms studied, only p38alpha and p38delta were detected in
      neutrophils. LPS stimulation selectively activated p38alpha. Specific inhibitors
      of p38alpha MAPk blocked LPS-induced adhesion, nuclear factor-kappa B (NF-kappaB)
      activation, and synthesis of tumor necrosis factor-alpha (TNF-alpha). Inhibition
      of p38alpha MAPk resulted in a transient decrease in TNF-alpha mRNA accumulation
      but persistent loss of TNF-alpha synthesis. These findings support a pathway by
      which LPS stimulation of neutrophils results in activation of MKK3, which in turn
      activates p38alpha MAPk, ultimately regulating adhesion, NF-kappaB activation,
      enhanced gene expression of TNF-alpha, and regulation of TNF-alpha synthesis.

PMID- 10079107
TI  - Inhibition of allorecognition by a human class II MHC-derived peptide through the
      induction of apoptosis.
AB  - The interaction of the T-cell receptor with the major histocomatibility complex
      (MHC)-peptide complex is central to T-cell activation. Variation in the nature of
      the peptide bound within the groove of the MHC molecule may result in an altered
      T-cell response. Because some naturally processed peptides bound within the
      groove of the class II MHC molecule are derived from the MHC molecules
      themselves, we studied the inhibitory effects of synthetic class II MHC peptides
      on alloimmune responses in vitro. Three peptides derived from a highly conserved
      region of the class II MHC alpha chains inhibited the rat mixed lymphocyte
      response (MLR) in a dose-dependent manner, with the human HLA-DQA1 peptide also
      inhibiting the human and mouse MLR. No effect was seen on mitogen-induced T-cell
      proliferation. HLA-DQA1 inhibited cytolytic T lymphocyte (CTL) generation in a
      dose-response fashion, with no reduction in preformed CTL killing, suggesting
      that the inhibitory effect is targeted at CD4(+) T-cell function. Cell-cycle
      analysis by flow cytometry showed that restimulation of primed T cells in the
      presence of HLA-DQA1 resulted in increased apoptosis, whereas unstimulated cells
      were not affected. These data demonstrate that synthetic peptides derived from
      highly conserved regions of the class II MHC alpha chain can alter CD4(+) T
      lymphocyte alloimmune responses in vitro, and this effect is mediated by the
      induction of apoptosis in activated T cells.

PMID- 10079108
TI  - Intracellular adhesion molecule-1 modulates beta-chemokines and directly
      costimulates T cells in vivo.
AB  - The potential roles of adhesion molecules in the expansion of T cell-mediated
      immune responses in the periphery were examined using DNA immunogen constructs as
      model antigens. We coimmunized cDNA expression cassettes encoding the adhesion
      molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function
      associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with
      DNA immunogens, and we analyzed the resulting antigen-specific immune responses.
      We observed that antigen-specific T-cell responses can be enhanced by the
      coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3.
      Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a
      significant enhancement of T-helper cell proliferative responses. In addition,
      coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a
      dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although
      VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any
      measurable effect on cell-mediated responses. These results suggest that ICAM-1
      and LFA-3 provide direct T-cell costimulation. These observations are further
      supported by the finding that coinjection with ICAM-1 dramatically enhanced the
      level of interferon-gamma (IFN-gamma) and beta-chemokines macrophage inflammatory
      protein-1alpha (MIP-1alpha), MIP-1beta, and regulated on activation normal T-cell
      expression and secreted (RANTES) produced by stimulated T cells. Through
      comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways
      are independent of CD86/CD28 pathways and that they may synergistically expand T
      cell responses in vivo.

PMID- 10079109
TI  - Protease-activated receptors 1 and 4 mediate activation of human platelets by
      thrombin.
AB  - Because of the role of thrombin and platelets in myocardial infarction and other
      pathological processes, identifying and blocking the receptors by which thrombin
      activates platelets has been an important goal. Three protease-activated
      receptors (PARs) for thrombin -- PAR1, PAR3, and PAR4 -- are now known. PAR1
      functions in human platelets, and the recent observation that a PAR4-activating
      peptide activates human platelets suggests that PAR4 also acts in these cells.
      Whether PAR1 and PAR4 account for activation of human platelets by thrombin, or
      whether PAR3 or still other receptors contribute, is unknown. We have examined
      the roles of PAR1, PAR3, and PAR4 in platelets. PAR1 and PAR4 mRNA and protein
      were detected in human platelets. Activation of either receptor was sufficient to
      trigger platelet secretion and aggregation. Inhibition of PAR1 alone by
      antagonist, blocking antibody, or desensitization blocked platelet activation by
      1 nM thrombin but only modestly attenuated platelet activation by 30 nM thrombin.
      Inhibition of PAR4 alone using a blocking antibody had little effect at either
      thrombin concentration. Strikingly, simultaneous inhibition of both PAR1 and PAR4
      virtually ablated platelet secretion and aggregation, even at 30 nM thrombin.
      These observations suggest that PAR1 and PAR4 account for most, if not all,
      thrombin signaling in platelets and that antagonists that block these receptors
      might be useful antithrombotic agents.

PMID- 10079110
TI  - Overexpression of a human potassium channel suppresses cardiac hyperexcitability
      in rabbit ventricular myocytes.
AB  - The high incidence of sudden death in heart failure may reflect abnormalities of
      repolarization and heightened susceptibility to arrhythmogenic early
      afterdepolarizations (EADs). We hypothesized that overexpression of the human K+
      channel HERG (human ether-a-go-go-related gene) could enhance repolarization and
      suppress EADs. Adult rabbit ventricular myocytes were maintained in primary
      culture, which suffices to prolong action potentials and predisposes to EADs. To
      achieve efficient gene transfer, we created AdHERG, a recombinant adenovirus
      containing the HERG gene driven by a Rous sarcoma virus (RSV) promoter. The
      virally expressed HERG current exhibited pharmacologic and kinetic properties
      like those of native IKr. Transient outward currents in AdHERG-infected myocytes
      were similar in magnitude to those in control cells, while stimulated action
      potentials (0.2 Hz, 37 degrees C) were abbreviated compared with controls. The
      occurrence of EADs during a train of action potentials was reduced by more than
      fourfold, and the relative refractory period was increased in AdHERG-infected
      myocytes compared with control cells. Gene transfer of delayed rectifier
      potassium channels represents a novel and effective strategy to suppress
      arrhythmias caused by unstable repolarization.

PMID- 10079111
TI  - Hypercholesterolemia decreases nitric oxide production by promoting the
      interaction of caveolin and endothelial nitric oxide synthase.
AB  - Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction
      caused in part by an impairment of endothelial nitric oxide (NO) production
      through mechanisms that remain poorly characterized. The activity of the
      endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by
      its reciprocal interactions with the stimulatory Ca2+-calmodulin complex and the
      inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce
      NO production through alteration of this regulatory equilibrium. Bovine aortic
      endothelial cells were cultured in the presence of serum obtained from
      normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure
      of endothelial cells to the HC serum upregulated caveolin abundance without any
      measurable effect on eNOS protein levels. This effect of HC serum was associated
      with an impairment of basal NO release paralleled by an increase in inhibitory
      caveolin-eNOS complex formation. Similar treatment with HC serum significantly
      attenuated the NO production stimulated by the calcium ionophore A23187.
      Accordingly, higher calmodulin levels were required to disrupt the enhanced
      caveolin-eNOS heterocomplex from HC serum-treated cells. Finally, cell exposure
      to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced
      the inhibition of basal and stimulated NO release, as well as the upregulation of
      caveolin expression and its heterocomplex formation with eNOS, which were
      unaffected by cotreatment with antioxidants. Together, our data establish a new
      mechanism for the cholesterol-induced impairment of NO production through the
      modulation of caveolin abundance in endothelial cells, a mechanism that may
      participate in the pathogenesis of endothelial dysfunction and the proatherogenic
      effects of hypercholesterolemia.

PMID- 10079112
TI  - Targeted mutation of plasma phospholipid transfer protein gene markedly reduces
      high-density lipoprotein levels.
AB  - It has been proposed that the plasma phospholipid transfer protein (PLTP)
      facilitates the transfer of phospholipids and cholesterol from triglyceride-rich
      lipoproteins (TRL) into high-density lipoproteins (HDL). To evaluate the in vivo
      role of PLTP in lipoprotein metabolism, we used homologous recombination in
      embryonic stem cells and produced mice with no PLTP gene expression. Analysis of
      plasma of F2 homozygous PLTP-/- mice showed complete loss of phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and partial loss
      of free cholesterol transfer activities. Moreover, the in vivo transfer of
      [3H]phosphatidylcholine ether from very-low-density proteins (VLDL) to HDL was
      abolished in PLTP-/- mice. On a chow diet, PLTP-/- mice showed marked decreases
      in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no
      significant change in non-HDL lipid or apo B levels, compared with wild-type
      littermates. On a high-fat diet, HDL levels were similarly decreased, but there
      was also an increase in VLDL and LDL phospholipids (210%), free cholesterol
      (60%), and cholesteryl ester (40%) without change in apo B levels, suggesting
      accumulation of surface components of TRL. Vesicular lipoproteins were shown by
      negative-stain electron microscopy of the free cholesterol- and phospholipid
      enriched IDL/LDL fraction. Thus, PLTP is the major factor facilitating transfer
      of VLDL phospholipid into HDL. Reduced plasma PLTP activity causes markedly
      decreased HDL lipid and apoprotein, demonstrating the importance of transfer of
      surface components of TRL in the maintenance of HDL levels. Vesicular
      lipoproteins accumulating in PLTP-/- mice on a high-fat diet could influence the
      development of atherosclerosis.

PMID- 10079113
TI  - In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse.
AB  - The accepted importance of circulatory impairment to sickle cell anemia remains
      to be verified by in vivo experimentation. Intravital microscopy studies of blood
      flow in patients are limited to circulations that can be viewed noninvasively and
      are restricted from deliberate perturbations of the circulation. Further
      knowledge of sickle blood flow abnormalities has awaited an animal model of human
      sickle cell disease. We compared blood flow in the mucosal-intestinal
      microvessels of normal mice with that in transgenic knockout sickle cell mice
      that have erythrocytes containing only human hemoglobin S and that exhibit a
      degree of hemolytic anemia and pathological complications similar to the human
      disease. In sickle cell mice, in addition to seeing blood flow abnormalities such
      as sludging in all microvessels, we detected decreased blood flow velocity in
      venules of all diameters. Flow responses to hyperoxia in both normal and sickle
      cell mice were dramatic, but opposite: Hyperoxia promptly slowed or halted flow
      in normal mice but markedly enhanced flow in sickle cell mice. Intravital
      microscopic studies of this murine model provide important insights into sickle
      cell blood flow abnormalities and suggest that this model can be used to evaluate
      the causes of abnormal flow and new approaches to therapy of sickle cell disease.

PMID- 10079114
TI  - Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1
      infection.

PMID- 10079115
TI  - Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse
      model of Alzheimer's disease.
AB  - The epsilon4 allele of apolipoprotein E (apo E) is associated with an increased
      risk for developing Alzheimer's disease (AD). This may be due to interactions
      between apo E and the amyloid-beta protein (Abeta). To assess the effects of
      human apo E isoforms on Abeta deposition in vivo, we bred apo E3 and apo E4
      hemizygous (+/-) transgenic mice expressing apo E by astrocytes to mice
      homozygous (+/+) for a mutant amyloid precursor protein (APPV717F) transgene that
      develop age-dependent AD neuropathology. All mice were on a mouse apo E null (-/
      ) background. By nine months of age, APPV717F+/-, apo E-/- mice had developed
      Abeta deposition, and, as reported previously, the quantity of Abeta deposits was
      significantly less than that seen in APPV717F+/- mice expressing mouse apo E. In
      contrast to effects of mouse apo E, similar levels of human apo E3 and apo E4
      markedly suppressed early Abeta deposition at nine months of age in APPV717F+/-
      transgenic mice, even when compared with mice lacking apo E. These findings
      suggest that human apo E isoforms decrease Abeta aggregation or increase Abeta
      clearance relative to an environment in which mouse apo E or no apo E is present.
      The results may have important implications for understanding mechanisms
      underlying the link between apo E and AD.

PMID- 10079116
TI  - Oxidation of methionine residues in coagulation factor VIIa.
AB  - The oxidation of the activated form of recombinant coagulation factor VII (FVIIa)
      by hydrogen peroxide has been studied. The three predominant oxidation products
      observed at pH 7.5 have been characterized as methionine sulfoxide derivatives of
      the parent protein involving two of the four methionine residues of the protein,
      Met298 and Met306. We conclude that oxidation of FVIIa with hydrogen peroxide
      only affects methionine residues and selectively oxidizes those which are readily
      accessible to the solvent. The oxidation process has been studied in the pH range
      3.5-9.5. The total rate of oxidation of FVIIa as well as the formation of the
      three oxidation products is consistent over the pH interval 7.5-9.5. However,
      under acidic conditions, significant variations have been observed indicating a
      conformational change of FVIIa. Oxidized FVIIa had the same amidolytic activity
      as the native protein. The binding to soluble tissue factor (TF) was weaker after
      oxidation as manifested by a threefold increase in dissociation constant and the
      amidolytic activity in complex with soluble TF was 80% compared to that of native
      FVIIa. In complex with lipid surface TF, the rate of factor X activation
      catalyzed by oxidized FVIIa was also reduced by approximately 20% compared to
      that of native FVIIa. However, native and oxidized FVIIa appeared to bind
      lipidated TF with indistinguishable affinities.

PMID- 10079117
TI  - Change of spatial field effects in 16- to 20-week-old infants.
AB  - Infants from 16 to 20 weeks were presented with objects moving across a 60-cm
      distance. Tracking increased between 16 and 18 weeks, reaching increased at 18
      weeks, and arm lifts (swipes) showed no age change. A right spatial field bias in
      tracking disappeared gradually. Swipes occurred most often in front of the
      object, when it was moving in the center field, presumably as reactions due to
      spatial proximity. Reaching occurred in the peripheral spatial fields in the
      younger infants, but in the older infants most often in the center spatial field.
      Moreover, reaching occurred generally more often toward the left spatial field
      and predicted the emergence of tracking the left spatial field. Thus, it appeared
      that a bias in reaching corrected a bias in tracking. Similar effects of limb
      movements, especially when reaching, were found in the successful treatment of
      visual neglect patients in neuropsychological research.

PMID- 10079118
TI  - Interhemispheric interaction affected by identification of Chinese characters.
AB  - One aspect of interhemispheric processing that has recently received attention is
      whether it increases or decreases the processing power of the brain. The present
      study investigated whether dividing information between the hemispheres becomes
      more advantageous to task performance as computational complexity increases. A
      Chinese character matching task was given to subjects involving three levels of
      computational complexity (the pairs of characters being divided into three types,
      visually similar, homonymous, and synonymous). The result showed no difference in
      performance between within-field and across-field presentation for visually
      similar characters. Performance was significantly better for across field than
      within field with homophones and synonyms. However, the error rates of within
      field for phonetic matching was significantly higher than those for semantic
      matching. These results suggest that both the computational difficulty of
      materials and the intrinsic function of each hemisphere play a role in
      interhemispheric processing.

PMID- 10079119
TI  - Fluency versus conscious recollection in category-production performance: the
      performance of schizophrenic patients.
AB  - The purpose of this study was to investigate the relative contribution in
      schizophrenics of automatic processes (fluency) and conscious processes
      (conscious recollection) for the control of preencoded material in category
      production tasks. In one condition (Exclusion condition), subjects were told
      specifically not to produce previously presented words during the category
      production task. This condition was compared with a standard category-production
      task in which subjects were told to produce the six first words that came to mind
      for a semantic category (Inclusion condition). In the inclusion condition, the
      effects of conscious control and automatic processes operated in the same
      direction, whereas in the exclusion condition automatic influences and conscious
      control were opposed. A recognition task followed the category-production tasks.
      Since the exclusion condition required conscious control of encoded items, we
      hypothesized that schizophrenic patients would be less able than control subjects
      to avoid producing study list items. These results indicated that schizophrenics'
      performance differed from these of control subjects in the exclusion condition
      but not in inclusion condition. Recognition performance was similar in both the
      schizophrenic and the control groups. These results suggest a defective conscious
      control in schizophrenic patients and confirm the data from the literature on
      explicit memory in these patients.

PMID- 10079120
TI  - Infantile spasms: facial expression of affect before and after epilepsy surgery.
AB  - This is a longitudinal study of facial expression of affect in 28 children with
      intractable infantile spasms who underwent epilepsy surgery. After a mean follow
      up period of 1.8 years, there was a significant increase in positive affect, a
      significant decrease in neutral affect, and no change in negative affect during a
      nonverbal communication paradigm. These findings were unrelated to surgical (i.
      e., side of surgery, type of surgery) or seizure-related variables (i.e., seizure
      control, age at onset of illness, duration of illness, change in antiepileptic
      drugs). Comparison of affect in a subgroup of 16 patients with those of 32 normal
      subjects suggest a normal age-related increase in the use of positive affect.
      Both before and after surgery, the patients used the most positive affect while
      not communicating. They also used significantly more positive affect during while
      requesting objects or assistance rather than during social referencing.
      Intractable infantile spasms might be associated with reduction in the facial
      expression of positive affect and with impaired use during social communication.

PMID- 10079121
TI  - Cross-modal priming and explicit memory in patients with verbal production
      deficits.
AB  - Implicit memory is often thought to reflect an influence of past experience on
      perceptual processes, yet priming effects are found when the perceptual format of
      stimuli changes between study and test episodes. Such cross-modal priming effects
      have been hypothesized to depend upon stimulus recoding processes whereby a
      stimulus presented in one modality is converted to other perceptual formats. The
      present research examined recoding accounts of cross-modal priming by testing
      patients with verbal production deficits that presumably impair the conversion of
      visual words into auditory/phonological forms. The patients showed normal priming
      in a visual stem completion task following visual study (Experiment 1), but
      showed impairments following auditory study in both implicit (Experiment 2) and
      explicit (Experiment 3) stem completion. The results are consistent with the
      hypothesis that verbal production processes contribute to the recoding of visual
      stimuli and support cross-modal priming. The results also indicate that shared
      processes contribute to both explicit memory and cross-modal implicit memory.

PMID- 10079123
TI  - Acknowledgment of guest reviewers january 1998-december 1998 

PMID- 10079124
TI  - Freeze-drying of red blood cells at ultra-Low temperatures.
AB  - The hemolysis of human red blood cells (RBCs) after freeze-drying and
      resuspension depends on the vacuum-drying temperature. In an experimental study,
      RBCs were first solidified based on a modified high-yield cryopreservation
      protocol in the presence of hydroxyethyl starch and maltose. Afterward, they were
      vacuum-dried in a special low-temperature freeze-drying device at selected shelf
      temperatures between -5 and -65 degrees C. Subsequently, the dried samples were
      resuspended in an isotonic, phosphate-buffered saline solution. The hemolysis was
      determined according to a modified saline stability test. It decreases with a
      decreasing shelf temperature until a minimum is reached at -35 degrees C. A
      further decrease of the shelf temperature has no beneficial effect; the hemolysis
      even increases. To interpret these results, we assume that the hemolysis depends
      on two contrary damaging effects: (1) the higher the shelf temperature, the
      higher the probability of structural damages occurring during drying; (2) the
      lower the shelf temperature, the lower the driving force for water transport;
      this may lead to an incomplete intracellular dehydration which means that the
      cells are not in a glassy state at ambient temperature.

PMID- 10079125
TI  - Cryostabilization mechanism of fish muscle proteins by maltodextrins 
AB  - Maltodextrins of varying mean molecular weights (MW) were evaluated for
      cryoprotective ability in Alaska pollock surimi (leached mince) versus sucrose or
      a sucrose-sorbitol mixture. Treatments were stored either isothermally at -8, 
      14, or -20 degrees C for 3 months or freeze-thaw (F/T) cycled six times to induce
      freeze-related protein denaturation, measured as a decrease in myosin Ca+2 ATPase
      activity and change in heat-induced gel-forming ability. Results indicated good
      cryoprotection by all maltodextrins at -20 degrees C isothermal storage
      irrespective of MW, but poor cryoprotection by higher MW maltodextrins at higher
      isothermal storage temperatures or after F/T cycling. These observations, and
      surface tension measurements of maltodextrin solutions, indicated that lower MW
      maltodextrins likely cryoprotect by a preferential solute exclusion mechanism,
      similar to sucrose and sorbitol. Higher MW maltodextrins presumably cryoprotect
      at lower storage temperatures via a reduced water mobility mechanism. As the MW
      of maltodextrins increased the gelling ability of the surimi was increasingly
      impaired, such that evidence of cryoprotection from gelation data was obscured.
      Copyright 1999 Academic Press.

PMID- 10079126
TI  - Viable spermatozoa can be recovered from refrigerated mice up to 7 days after
      death.
AB  - To develop a model for utilizing germ cells collected from dead animals, male
      mice were euthanized and refrigerated for various periods, and the viability of
      the epididymal spermatozoa was examined by in vitro fertilization, embryo
      culture, and embryo transfer. Higher proportions of fresh oocytes were fertilized
      when males had been stored at 4-6 or 8-10 degrees C than at 0 degrees C. By
      partially dissecting the zona of freshly ovulated oocytes, spermatozoa from ICR
      male mice could fertilize oocytes (21% fertilization rate) after being stored for
      5 days at 4-6 degrees C, and spermatozoa from BDF1 male mice could fertilize
      oocytes (39%) after being stored for 7 days at 4-6 degrees C. The resulting two
      cell embryos had the ability to develop into expanded blastocysts in culture (81
      100%) and into live young after transfer (34-47%). With further refinement of
      this system, it should be applicable not only for rescuing valuable genetic
      variants in laboratory animals or livestock animals but also for wild species in
      the future.

PMID- 10079127
TI  - Kinetic and temporal factors influence chilling injury to germinal vesicle and
      mature bovine oocytes.
AB  - In this study we examined the effects of low, above freezing temperatures on the
      viability and functionality of bovine oocytes. Germinal vesicle (GV) stage and in
      vitro matured oocytes (MII) were exposed to various combinations of time (15 and
      60 min) and temperature (4, 16, 23, and 39 degrees C). After being treated, the
      ability of oocytes to undergo maturation and fertilization in vitro was examined,
      as well as their viability assayed by two fluorescent probes, fluorescein
      diacetate (FDA) and 5-carboxyfluorescein diacetate (cFDA). Cooling GV oocytes to
      16 degrees C for 15 min reduced the fertilization rate by more than 40%, compared
      with those left at 39 degrees C. Surprisingly, cooling oocytes to 4 degrees C
      reduced the fertilization rate by only 10% compared with control. Exposing GV
      oocytes to temperatures below 23 degrees C reduced their viability. Similar to
      the reduction in fertilization, the viability of GV oocytes after exposure to 16
      degrees C was reduced by more than 50%, whereas exposure to 4 degrees C reduced
      it by only 9%. Viability measurements using FDA and cFDA gave comparable results
      and showed a similar trend. The viability of MII oocytes and of GV oocytes
      pretreated with butylated hydroxytoluene, following exposure to low temperatures,
      was higher compared with that of GV controls. We interpret these results as
      indicating chilling effects on membrane integrity. Improving the chilling
      resistance of bovine oocytes may facilitate their short- and long-term
      preservation.

PMID- 10079128
TI  - Cold hardiness adaptations of codling moth, cydia pomonella 
AB  - The cold hardiness adaptations of natural and laboratory reared populations of
      the codling moth, Cydia pomonella, were examined. Hemolymph, gut, and whole body
      supercooling points (SCPs), 24-h LT50s, polyhydroxy alcohol concentrations,
      hemolymph freezing points, and hemolymph melting points were determined.
      Nondiapausing codling moth larvae do not have appreciable levels of ice
      nucleators in the hemolymph or gut. Whole body supercooling points were higher
      than hemolymph supercooling points. For nondiapausing larvae, LT50s were
      significantly higher than both the whole body and the hemolymph supercooling
      points, indicating the presence of chill sensitivity. As the larvae left the food
      source and spun a cocoon, both hemolymph and whole body SCPs decreased. Diapause
      destined larvae had significantly lower hemolymph SCPs than nondiapausing larvae,
      but whole body SCPs were not significantly different from nondiapausing larvae of
      the same age. The LT50s of diapause destined and diapausing larvae were
      significantly lower than that of nondiapausing larvae. Codling moths are freezing
      intolerant, with LT50s close to the average whole body supercooling point in
      diapause destined and diapausing larvae. The overwintering, diapausing larvae
      effectively supercool to avoid lethal freezing by removal of ice nucleators from
      the gut and body without appreciable increase of antifreeze agents such as
      polyols or antifreeze proteins.

PMID- 10079129
TI  - Evaluation of the impedance technique for cryosurgery in a theoretical model of
      the head.
AB  - Bioimpedance is a noninvasive technique that produces information on the
      electrical characteristics of tissue inside the body from currents injected and
      electrical potentials measured on the surface of the body. Because freezing
      causes a large increase in tissue electrical impedance we thought that it may
      also cause significant changes in the surface electrical potential making the
      bioimpedance technique suitable for noninvasive monitoring and imaging of
      cryosurgery. To evaluate the feasibility of the bioimpedance technique in
      cryosurgery we examined, as a case study, a theoretical model for the electrical
      potentials during brain cryosurgery. A three-dimensional spherical model was used
      to calculate the change in the electrical potential distribution in the head as a
      function of the current source location and the size of the frozen lesion in the
      brain. The numerical calculations were executed using the finite volume method
      and the iterative successive over relaxation method. The results demonstrate
      that, indeed, freezing inside the head produces measurable changes in the
      electrical potential on the outer surface-the scalp.

PMID- 10079130
TI  - Ice-nucleating bacteria from the guts of two sub-antarctic beetles, hydromedion
      sparsutum and perimylops antarcticus (Perimylopidae) 
AB  - The site of ice nucleation in the freeze-tolerant, sub-Antarctic beetle
      Hydromedion sparsutum has been investigated. Ice+ bacteria, active at above -2.0
      degrees C, were isolated from the guts of beetles and identified as a fluorescent
      Pseudomonas species. Other possible sites of nucleation, including the hemolymph,
      were examined but had a lower activity. Ice+ bacteria were isolated from mixed
      populations, isolated from the guts of adult beetles, and grown on nutrient agar
      plates and in nutrient broth. Nucleation activity of the broth culture peaked
      after only 2 days although the number of live cells continued to increase until
      day 6. These cultures were used to determine the maximum nucleation activity of a
      bacterial suspension in sterile distilled water (-3.4 degrees C) and the dilution
      factor required to cause a 50% reduction in activity (10(4)). The original
      bacterial suspension had an absorbance of 0.5 measured at 660 nm and contained 6
      x 10(11) bacteria per milliliter. From this it is estimated that only 1 in 10(6)
      bacteria possessed the highest levels of ice-nucleating activity. Other insect
      species, including Perimylops antarcticus, which are found in habitats similar to
      that of H. sparsutum, were examined for the presence of ice+ bacteria. All
      contained ice-nucleating bacteria in their guts but with a lower level of
      activity than in H. sparsutum. Copyright 1999 Academic Press.

PMID- 10079131
TI  - Role of intracellular buffering power on the mitochondria-cytosol pH gradient in
      the rat liver perfused at 4 degrees C.
AB  - The factors regulating the amplitude and the pH gradient between cytosol and
      mitochondria (DeltapHmito-cyt) were investigated in the isolated rat liver
      perfused at 4 degrees C. Liver ATP content, pH, and buffering power of cytosolic
      and mitochondrial compartments were evaluated in situ using phosphorus-31 nuclear
      magnetic resonance spectroscopy. No DeltapHmito-cyt was detected in the liver
      perfused without bicarbonate. Permeant weak acid in the perfusate (H2CO3, 25 mM,
      or isobutyric acid, 25, 50, or 100 mM) acidified both cytosol and mitochondria
      and revealed a DeltapHmito-cyt from 0.06 to 0.31 pH unit. Nevertheless, the
      manipulations of the DeltapHmito-cyt were more effective under bicarbonate-free
      conditions, due to the absence of buffering by H2CO3/HCO-3. In the absence of
      bicarbonate, the intracellular buffering power was threefold higher in the
      mitochondria (110 mmol/pH unit at pHmito 7.16) than in the cytosol (44 mmol/pH
      unit at pHcyt 7.30) and dependent on the matrix and cytosol pH, respectively.
      These buffering powers were almost double in the presence of bicarbonate. In the
      bicarbonate-free perfused liver, the respiratory activity was 0.08 +/- 0.02
      micromol O2/min. g liver wet weight and the ATP turnover was only 40 +/- 7
      nmol/min. g liver wet weight, indicating the weak activity of liver mitochondria
      when DeltapHmito-cyt was <0.05 pH unit. The ATP turnover during a 50 mM
      isobutyric acid load was 35 +/- 4 nmol/min. g liver wet weight whereas
      DeltapHmito-cyt rose to 0.26 +/- 0.02 pH unit and pHmito remained alkaline.
      Hence, although DeltapHmito-cyt was increased the ATP turnover remained
      unchanged. This work is the first evaluation of the mitochondrial buffering power
      in the isolated liver. The DeltapHmito-cyt observed within various acid loads
      reflected the differential titration of cytosol and mitochondria containing
      proteins and H2CO3/HCO-3 buffering systems. Moreover, no direct relationship
      between DeltapHmito-cyt and ATP turnover could be shown.

PMID- 10079132
TI  - Seasonal changes in the freezing behavior of xylem ray parenchyma cells in four
      boreal hardwood species 
AB  - The freezing behavior of xylem ray parenchyma cells in several boreal hardwood
      species, namely, Betula platyphylla, Populus canadensis, P. sieboldii, and Salix
      sachalinensis, was examined by differential thermal analysis (DTA), cryo-scanning
      electron microscopy (Cryo-SEM), and freeze-fracture replica electron microscopy.
      Although DTA profiles of samples harvested in summer and in winter suggested that
      the xylem ray parenchyma cells in all four species responded to freezing stress
      by extracellular freezing, Cryo-SEM showed clearly that the xylem ray parenchyma
      cells in all these species responded to freezing stress by shallow supercooling
      in summer and by extracellular freezing in winter. It is suggested that DTA
      failed to reveal the true freezing behavior of xylem ray parenchyma cells because
      of an overlap of temperature ranges between the high-temperature exotherm and the
      low-temperature exotherm and/or because of the limited extent of the LTE. The
      seasonal changes in freezing behavior of xylem ray parenchyma cells in all these
      boreal species, which are results of seasonal cold acclimation, support the
      hypothesis that a gradual shift of freezing behavior in xylem ray parenchyma
      cells from shallow supercooling in hardwood species that grow in tropical zones
      to extracellular freezing in hardwood species that grow in cold areas might be a
      result of the evolutionary adaptation of hardwood species to cold climates.
      Copyright 1999 Academic Press.

PMID- 10079133
TI  - Percutaneous cryoablation of the kidney in a porcine model.
AB  - Several reports have documented that renal cryoablation when used either via open
      or laparoscopic surgical techniques can be well tolerated in animal models. We
      sought to examine the feasibility of performing renal cryoablation
      percutaneously, under ultrasound guidance, in a porcine model. A total of 13
      juvenile swine was treated. In each animal the lower pole of the left kidney was
      used as the target. Each animal had serum drawn for Hct, Wbc, CK, BUN,
      creatinine, and myoglobin pre- and postcryoablation and again at the time of
      sacrifice. Animals were sacrificed at 0-42 days postoperatively, and the treated
      renal units were harvested and submitted for histologic examination. The
      procedures were divided into three groups based on the extent of the freeze time.
      Group 1 (n = 4) was treated for 3-4 min, single freeze; Group 2 (n = 3), 6-7 min,
      single freeze; and Group 3 (n = 6), a double freeze-thaw cycle, each for 10 min.
      None of the animals in this experiment died or experienced significant clinical
      deteriorations at any time post-treatment. No significant differences in any of
      the measured serum markers were noted between pre- and post-treatment values. For
      animals in Groups 1 and 2 discrete cryolesions were created with sharp 1-mm
      borders and no perirenal reaction/damage to surrounding structures. For animals
      in Group 3 large areas of renal infarction/cryolesions were produced, with
      significant perirenal reaction in 5/6 animals and gross hydronephrosis/total
      renal loss in 2/6. Percutaneous renal cryoablation appears to be well tolerated
      in the porcine model which we used. Associated morbidity appears to be related to
      the extent of freezing, with a safety tolerance in the present study limited to
      target areas of approximately 3-5 cm3. These findings suggest that a pilot study
      of percutaneous renal cryoablation for patients with 3-4-cm exophytic lesions may
      be warranted.

PMID- 10079134
TI  - Evidence to suggest morphological and physiological alterations of lacrimal gland
      acini with ageing.
AB  - This study investigates changes in the morphology and physiology of lacrimal
      gland acinar cells with age. Changes in microstructural appearance of the acinar
      cells, the type and distribution of the different acini in glands and the
      secretory granules within the acini were examined in glands from animals of 3-5,
      9, 12, 20, 24 and 28 month old rats. Differences in the secretory capacity of the
      acinar cells were also examined in animals of each age-group, with the exception
      of 28 months. The typical acini of young glands (3-5 months) were of the serous
      type. This was also true of 9 month glands, although there was a significant
      reduction in their overall distribution compared to young glands. The acini in
      the 12 month glands were predominantly of the seromucous type and appeared to be
      at the expense of the serous acini which were further significantly reduced
      compared to 3-5 and 9 month glands. This remained the prevalent acini type in 20
      month glands, however by 24 months there was a significant increase in the
      occurrence of mucous acini and this time appeared to be at the expense of the
      seromucous acini which were significantly reduced in glands of this age-group.
      The predominant acinar cell in 28 month glands, like 24 month glands, was of the
      mucous variety. Qualitative EM studies revealed a progressive change in the
      secretory products of the lacrimal gland acini, strongly correlating to changes
      in acinar cell type. Typical acini of both 3-5 and 9 month glands contained
      numerous protein secretory granules. The seromucous acini also of these age
      groups contained both protein and mucous secretory granules, with the protein
      secretory granules in higher abundance. By 12 months the typical seromucous acini
      was packed with both protein and mucous secretory granules of equal proportions.
      However, by 20 months the predominant seromucous acini contained fewer protein
      secretory granules and elevated occurrence of mucous secretory granules. By 24
      and 28 months the acini contained even fewer protein secretory granules and the
      typical acinar cell was of the mucous type containing exclusively mucous
      secretory granules. The secretory capacity of the acini was also altered with
      age. Maximum protein output in response to cholinergic stimulation resulted in an
      initial significant increase with ageing from 3-5 months to 9 and 12 months
      followed by a later significant age-dependent reduction in output. However,
      maximal peroxidase release from acinar cells of 3-5 and 9 month glands was the
      same. This was followed by a significant age-dependent reduction in peroxidase
      release. Furthermore, the concentrations required to evoke these responses
      differed with age. These results present evidence to suggest that acinar cells of
      the lacrimal gland undergo progressive alterations with age. The type of acini
      changing initially from serous to seromucous acini (intermediate phase) followed
      by a gradual transformation of the seromucous acini to mucous acini. This in turn
      changes the properties of the acini from protein producing and secreting acini to
      mucous producing and secreting acini. The results also suggest a reduction in the
      ability of the acini to synthesise proteins with age and altered responsiveness
      to cholinergic stimulation to secrete proteins. These findings may help in
      explaining the occurrence of altered protein/tear secretion with ageing.

PMID- 10079135
TI  - The influence of tissue culture on corneal immunogenicity.
AB  - In this study we examined whether immunization with heterotopic corneal graft can
      be suppressed by usage of cultured corneal tissue. Starting from the hypothesis
      that the corneal antigenicity might change during long-time storage, we compared,
      in a mouse model, the immunization obtained with fresh and> stored corneas.
      Heterotopic (chest wall) mice corneal allografts were exchanged between donors
      and hosts: (1) mismatched at multiple minor H loci and (2) only H-Y mismatched
      animals. Median survival time (MST) of primary and secondary skin grafts
      exchanged between mentioned donors and hosts was recorded. Recipient mice were
      immunized with either: (a) tail-skin graft, (b) fresh cornea graft or (c) corneal
      graft stored for three weeks in tissue culture. Three weeks later, recipients
      were challenged with skin graft placed at the opposite side of the chest wall and
      MST of these skin grafts was recorded. MST of secondary skin grafts in animals
      that had been immunized by skin served as a control. In case of multiple minor H
      disparity, MST of a first-set skin graft was 12 days, as compared to 9 days in
      case of secondary skin graft (P<0.05). MST of secondary skin graft following
      immunization by both fresh and stored corneas was 10 days. These data suggest
      that stored corneas don't loose ability to sensitize the multiple minor H
      disparate host. It also show that both cultured and fresh corneas, when placed in
      non-privileged site, have same immunizing capacity as skin (MST of 10 and 9 days,
      respectively; P>0. 1). When only H-Y disparate animals were used, MST of a first
      set skin grafts was 26 days and of secondary skin graft 11 days (P<0.01). In case
      of H-Y disparity, MST obtained after immunization with fresh and stored corneal
      tissue (19 and 18 days, respectively) was significantly longer as compared to
      skin (P<0.05). However, no significant difference in MST of secondary skin grafts
      between recipients of fresh (19 days) and stored corneal grafts (18 days) was
      recorded. According to our results, the ability of corneal tissue to immunize
      both multiple minor H mismatched, as well as only H-Y mismatched host, was not
      influenced by storage in a tissue culture.

PMID- 10079136
TI  - Enhanced expression of a transmembrane phosphotyrosine phosphatase (LAR) in
      keratoconus cultures and corneas.
AB  - The purpose of the study was to identify genes that are differentially expressed
      in normal versus keratoconus corneas. Total RNA isolated from corneal stromal
      cell cultures was reverse-transcribed and then amplified by the polymerase chain
      reaction (PCR) using defined, arbitrary primers. The products were displayed on
      polyacrylamide gels and bands that were differentially expressed were excised, re
      amplified and subcloned. The resulting clones were sequenced and utilized as
      probes for Northern blots with cultured cell RNA or Southern blots of corneal
      cDNA. One of the products that appeared to be more highly expressed in
      keratoconus cultures and corneas displayed 100% homology with leukocyte common
      antigen related protein (LAR), a transmembrane phosphotyrosine phosphatase.
      Western analyses and immunohistochemistry with monoclonal and/or polyclonal
      antibodies to LAR were used to examine keratocyte cultures and fresh frozen
      normal, keratoconus and pseudophakic bullous corneas. We identified a gene
      product with 100% homology to LAR that is expressed at the RNA level in
      keratoconus corneas and cell cultures but is found only at low or undetectable
      levels in normal cultures and normal and pseudophakic bullous keratopathy (PBK)
      corneas. By Western blotting and immunofluorescence with specific LAR antibodies,
      the protein was identified in keratoconus stromal cell cultures but not in normal
      cultures. When fresh frozen tissue was examined, LAR protein was localized to
      numerous stromal cells throughout central keratoconus corneas, while no central
      staining was seen in normal or bullous keratopathy corneas. LAR, a transmembrane
      phosphotyrosine phosphatase, is more highly expressed in keratoconus corneas and
      stromal cell cultures as demonstrated by differential display, Northern analyses,
      immunohistochemistry and Western blotting.

PMID- 10079137
TI  - Corneal epithelium-specific mouse keratin K12 promoter.
AB  - Keratins are structural proteins expressed by epithelial cells. Approximately 30
      different keratin proteins have been identified, each with a specific expression
      pattern in different epithelial cells. The tissue-specific promoter of several
      keratin genes have been used to direct the expression of transgenes in animals.
      Keratin K12 and K3 are expressed in differentiated and stratified corneal
      epithelium, although the relative expression of each appears to vary between
      species. We targeted the mouse K12 keratin gene in order to develop a tissue
      specific promoter that could be utilized to study the functions of genes of
      interest expressed in the corneal epithelium. Three 5' truncated fragments of the
      keratin K12 promoter (1.03, 0.71 and 0.25 Kb) showed higher functional and tissue
      specific promoter activity in a human corneal epithelial cell line than other
      cell lines. The 0.25 Kb K12 promoter fragment was also active in cultured rabbit
      corneal epithelial cells. Thus, increased expression in corneal epithelial cells
      directed by fragments of the mouse K12 promoter extended across species lines.
      The paired box homeotic gene 6 (PAX-6), which is involved in controlling eye
      development, stimulated the activity of keratin K12 promoter.

PMID- 10079138
TI  - Proteoglycans on normal and migrating human corneal endothelium.
AB  - Proteoglycans are of fundamental importance to the normal functioning of the
      cornea. They consist of a core protein to which one or more glycosaminoglycan
      chains are attached. Cell surface proteoglycans are known to mediate many aspects
      of cell behaviour including cell adhesion, control of extracellular matrix
      deposition, cell proliferation, cell migration, leukocyte adhesion and modulation
      of growth factor activity. This paper describes the first investigation into the
      distribution and function of the three main classes of proteoglycans on human
      corneal endothelium. Immuno-gold labelling techniques were used at the light,
      scanning and transmission electron microscope level to localise heparan sulphate,
      chondroitin sulphate and keratan sulphate proteoglycans on human corneal
      endothelium. Human corneas were freeze-wounded and kept in organ culture for 3
      days in order to study the distribution of proteoglycans on migrating corneal
      endothelium. An Optimas image analysis system was used to quantify the change in
      proteoglycan labelling during cell migration. Labelling for chondroitin sulphate
      and heparan sulphate was at very low levels on normal corneal endothelium while
      keratan sulphate labelling was at high levels. The wound healing experiments
      showed that migrating cells had increased labelling for heparan sulphate and
      chondroitin sulphate with greatly decreased labelling for keratan sulphate.
      Statistical analysis showed these changes were highly significant (P<0.001).
      Transmission electron microscopy revealed that chondroitin sulphate and keratan
      sulphate were present throughout Descemet's membrane while heparan sulphate was
      concentrated at the interface of Descemet's membrane and the migrating corneal
      endothelial cells. The pattern of occurrence of chondroitin sulphate, heparan
      sulphate and keratan sulphate on the human endothelium in normal and wounded
      cornea suggests that these proteoglycans are linked to the process of cell
      migration.

PMID- 10079139
TI  - Optic nerve changes in manganese-deficient rats.
AB  - In the present study the changes in the optic nerve due to dietary manganese (Mn)
      deficiency has examined in Wistar Kyoto rats, since there is a lack of
      information on the significance of manganese in the optic nerve. After 5 months
      on a Mn-deficient diet, the optic nerve was examined by light and transmission
      electron microscopy. The serum manganese level of the deficient rats was
      significantly lower than that of the controls. The light microscopic findings
      showed significantly fewer myelinated axons in the Mn-deficient rats and Mn
      recovery rats than in the control group, and there were obviously more
      oligodendrocytes in the recovery rats. Ultrastructural findings were:
      significantly decreased diameters and lamellae of myelinated axons in the optic
      nerves of the Mn-deficient rats and abnormal mitochondria in the axons. Rats fed
      a normal diet for 3 months after 5 months on a Mn deficient diet had a normal
      serum manganese level, but no change in the abnormal morphology of the myelinated
      axons. It is concluded that the optic nerve needs manganese for the maintenance
      of its cell structure.

PMID- 10079140
TI  - Disruption of the Sparc locus in mice alters the differentiation of lenticular
      epithelial cells and leads to cataract formation.
AB  - SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein
      that regulates cellular adhesion and proliferation. In this report, we show that
      SPARC protein is restricted to epithelial cells of the murine lens and ends
      abruptly at the equatorial bow region where lens fiber differentiation begins.
      SPARC protein was not detected in the lens capsule or in differentiated lens
      fibers. SPARC-null mice developed cataracts at approximately 3-4 months after
      birth, at which time posterior subcapsular opacities were observed by slit lamp
      ophthalmoscopy. Histological analyses of ocular sections from 3-month old animals
      revealed several microscopic abnormalities present in the SPARC-null mice but
      absent from the wild-type animals. Fiber cell elongation was incomplete
      posteriorly and resulted in displacement of the lenticular nucleus to the
      posterior of the lens. Nuclear debris was present in the posterior subcapsular
      region of the lens, an indication of the abnormal migration and elongation of
      either fetal or anterior epithelial cells, and the bow region was disrupted and
      vacuolated. In the anterior lens, the capsule appeared to be thickened and was
      lined by atypical, plump cuboidal epithelium. Moreover, anterior cortical fibers
      were swollen. Polyacrylamide gel electrophoresis of the epithelial, cortical and
      nuclear fractions of wild-type and SPARC-null lenses indicated no significant
      differences among the alpha-, beta-, and gamma-crystallins. Expression of alphaB
      crystallin appeared similar in fiber cells of wild-type and SPARC-null lenses,
      although the distribution of alphaB-crystallin was asymmetric in SPARC-null
      lenses as a result of abnormal lens fiber differentiation. No evidence of
      atypical extracellular matrix deposition in areas other than the capsule was
      detected in wild-type or SPARC-null lens at 3 months of age. We conclude that the
      disruption of the Sparc locus in mice results in the alteration of two
      fundamental processes of lens development: differentiation of epithelial cells
      and maturation of fiber cells.

PMID- 10079141
TI  - Role and regulation of IL-8 and MCP-1 in LPS-induced uveitis in rabbits.
AB  - Intravitreal injection of lipopolysaccharide (LPS) induces leukocyte infiltration
      and protein leakage into the aqueous humor. In the present study, we investigated
      the role of IL-8 and MCP-1 and regulation of these chemokines by TNFalpha and IL
      1 in LPS-induced uveitis in rabbits. After intravitreal injection of LPS,
      generation of IL-8 in the aqueous humor showed a biphasic pattern with the first
      peak at 12 hr and the second one at 24 hr, while MCP-1 was produced in a
      monophasic pattern and peaked at 24 hr. Immunohistochemistry showed that ciliary
      epithelial cells and infiltrating leukocytes were the producing cells of IL-8 and
      MCP-1. Administration of anti-IL-8 IgG suppressed by 66% the peak levels of LPS
      induced aqueous neutrophil counts at 24 hr but did not suppress aqueous
      mononuclear cell counts or protein levels. anti-MCP-1 IgG inhibited aqueous
      mononuclear cell counts by 41% and protein levels by 28%, but did not inhibit
      aqueous neutrophil counts. The levels of LPS-induced aqueous IL-8 and MCP-1 at 12
      hr were inhibited by anti-TNFalpha mAb but not by an IL-1 receptor antagonist (IL
      1Ra), while concentrations of the two chemokines at 24 hr were inhibited by both
      anti-TNFalpha mAb and IL-1Ra. A combination of anti-TNFalpha mAb and rrIL-1Ra had
      an additive effect on the 24 hr-chemokine levels and inhibited up to 90%
      chemokine production. Taken together, our results show that IL-8 mediates
      neutrophil infiltration, while MCP-1 mediates mononuclear cell infiltration and
      protein leakage in LPS-induced uveitis in rabbits. Levels of aqueous IL-8 and MCP
      1 at 12 hr are regulated by TNFalpha, while levels at 24 hr are regulated by
      TNFalpha and IL-1.

PMID- 10079142
TI  - Analysis of sex-mismatched human corneal transplants by fluorescence in situ
      hybridization of the sex-chromosomes.
AB  - The fate of the cells of corneal transplants has been controversial from the
      early days of keratoplasty. Various methods such as histological evaluation,
      radiolabeling of donor cells or Barr-body analysis have been applied to clarify
      the issue. However, the question whether the transplanted cells are replaced or
      survive, remains unsolved. In this study, we applied fluorescence in situ
      hybridization (FISH) of the X- and Y-chromosomes in paraffin sections of
      explanted sex-mismatched corneal transplants to distinguish between host and
      donor cells. Fourteen sex-mismatched cases with various reasons for explantation
      and different postoperative time intervals ranging from 11 months to 30 years
      were analysed. We found that all cell types, including epithelium, keratocytes
      and endothelial donor cells were replaced in most cases as early as 1 year after
      transplantation. In three cases, however, up to 26% of donor keratocytes were
      still detected up to 4.5 years after transplantation, demonstrating a certain
      individual variability in the process of replacement. Further studies must show
      if the extent and timing of donor cell replacement in clinically successful,
      totally clear transplants is different. Our results are in keeping with the
      phenomenon of recurrences of corneal dystrophies in the graft, the significant
      postoperative decline of the endothelial cell density, the fact that typical
      graft rejections usually take place within 1-2 years postoperatively and that
      relatively late rejections can occur in rare cases probably due to some surviving
      stromal keratocytes. Donor cell replacement is a special feature of corneal
      transplants when compared with other kinds of organ transplants and might be due
      to the presence of the same tissue type in the immediate neighbourhood of the
      graft.

PMID- 10079143
TI  - Protective effect of pirenoxine and U74389F on induced lipid peroxidation in
      mammalian lenses. An in vitro, ex vivo and in vivo study.
AB  - Oxidative stress is believed to be involved in cataract development. The
      protective effect of the xanthomatine derivative, pirenoxine, and the 21
      aminosteroid U74389F on oxidative insult in mammalian lenses was evaluated in
      vitro, ex vivo and in vivo. In vitro pirenoxine and U74389F inhibited lipid
      peroxidation induced by iron or haemoglobin in guinea-pig homogenate lens or
      whole lenses. Both compounds produced the same effect when lens oxidation was
      induced by superoxide producing system such as xanthine/xanthine oxidase or fMLP
      stimulated macrophages. In all the in vitro experiments, the values of
      biochemical lipid peroxidation markers, such as lipid hydroperoxides or
      thiobarbituric reactant substances, fell to the basal values with the addition of
      either pirenoxine (10(-5) M) or U74389F (10(-5) M). When two drops (60 microl) of
      the above molecular solutions (0.005 and 0.012% in saline respectively) were
      instilled in rabbit eyes (every hour for 8 hours over 2 days), the extracted
      lenses appeared to have better defences against an in vitro iron-induced lipid
      peroxidation, as shown by the values of conjugated dienes and lipid soluble
      fluorescent substances. These values also proved to be significantly lower when
      the same parameters were assayed in lenses from eyes where a lipid peroxidation
      was induced in vivo by haemoglobin or Diquat intravitreal injection followed by
      instillations of pirenoxine sodium salt or U74389F solutions (2 drops of about 60
      microl every hour for 8 hours over 4 days) administered topically. Polarographic
      and chronocoulometric measurements were also performed in order to investigate
      the action mechanisms of both compounds. Experimental data indicate that the
      pirenoxine sodium salt and U74389F may be considered effective tools for
      rejecting an oxidative attack on the lenses, which can finally lead to cataract
      formation.

PMID- 10079144
TI  - Relationship between autofluorescence and advanced glycation end products in
      diabetic lenses.
AB  - Autofluorescence and advanced glycation end product (AGE) levels were measured in
      the lenses of 9 diabetic Chinese hamsters and 6 age-matched controls. Lens
      autofluorescence also was measured in 37 diabetic patients and 14 age-matched
      controls. Lens autofluorescence values were measured noninvasively with a lens
      measurement system using color filters with peak transmission at 365- and 434-nm
      wavelengths (excitation and emission, respectively) that are characteristic of
      AGE fluorescence. The peak lens autofluorescence level was used as the lens
      autofluorescence value, and the mean lens autofluorescence values from both eyes
      of each subject were used for statistical analysis. The AGE levels in one lens
      from each hamster were measured by noncompetitive enzyme-linked immunosorbent
      assay with a polyclonal anti-AGE antibody. We found a 2.2 times increase of the
      mean lens autofluorescence value of diabetic hamsters in comparison with that of
      controls (P<0.01). We also found a 1.5 times increase of the mean AGE level from
      the lenses of diabetic hamsters in comparison with that of controls (P<0.01).
      Moreover, a statistically significant positive correlation between the AGE level
      and autofluorescence value in the same lenses was observed in all hamsters
      (rho=0.58, P<0.05). In human subjects, we found a 1.4 times increase of the mean
      lens autofluorescence value of diabetic patients in comparison with that of age
      matched controls (P<0.01). Our results suggest that non invasive measurement of
      lens autofluorescence may be a guide to AGE levels in lenses.

PMID- 10079145
TI  - An adenosine analogue inhibits NMDA receptor-mediated responses in bipolar cells
      of the rat retina.

PMID- 10079147
TI  - Announcements 

PMID- 10079146
TI  - Integrity and distribution of HMG CoA reductase mRNA in lens: relationship to
      cessation of membrane formation.

PMID- 10079148
TI  - ANTI-INFLAMMATORY ACTIVITY OF PHYCOCYANIN EXTRACT IN ACETIC ACID-INDUCED COLITIS
      IN RATS.
AB  - The anti-inflammatory effect of c-phycocyanin extract was studied in acetic acid
      induced colitis in rats. Phycocyanin (150, 200 and 300 mg kg-1 p.o.) was
      administered 30 min before induction of colitis with enema of 1 ml of 4% acetic
      acid per rat. Twenty-four hours later myeloperoxidase (MPO) activity was
      determined as well as histopathological and ultrastructural studies were carried
      out in colonic tissue. Phycocyanin substantially reduced MPO activity which was
      increased in the control colitis group. Also, histopathological and
      ultrastructural studies showed inhibition in inflammatory cell infiltration and
      reduction to some extent in colonic damage in rats treated with phycocyanin. The
      probable role of antioxidative and the scavenging properties of phycocyanin
      against reactive oxygen species in the anti-colitic effect is discussed in this
      paper. To our knowledge this is the first report on the anti-inflammatory effect
      of phycocyanin in an experimental model of colitis.(c) 1999 The Italian
      Pharmacological Society.

PMID- 10079149
TI  - New Vibrational Numbering and Potential Energy Curve for the 3(3)Pig Electronic
      State of the Li2 Molecule.
AB  - An experimental study of the 3(3)Pig electronic state of 7Li2, using the
      Perturbation-Facilitated Optical-Optical Double Resonance (PFOODR) technique, was
      recently reported [A. Yiannopoulou et al., J. Chem. Phys. 103, 5898, (1995)].
      However, due to the very small number of known 7Li2 A1Sigma+u approximately b3Piu
      window levels, only 13 ro-vibrational levels (spanning a range of vibrational
      levels designated upsilonx - 1 to upsilonx + 3 in that reference) could be
      observed. Dunham coefficients, based on the assignment upsilonx = 7, were found
      to fit the observed term values and give a qualitative fit to the intensities of
      the first six lines of the 3(3)Pig (upsilon = upsilonx, N = 11) --> b3Piu
      emission spectrum. However, due to the limited number of levels used in the fit,
      both the absolute vibrational numbering and the 3(3)Pig RKR potential curve
      obtained from the Dunham coefficients, must be considered to be uncertain. In the
      present work, we show that the previously reported 3(3)Pig RKR curve is unable to
      reproduce the experimental intensity distribution in the 7Li2 3(3)Pig (upsilonx =
      7, N = 11) --> a3Sigma+u emission continuum. We report new experimental data for
      the 7Li2 3(3)Pig (upsilonx + 1, N = 11) --> a3Sigma+u bound-free continuum and
      discrete 3(3)Pig (upsilonx +/- 1, N = 11) --> b3Piu spectra obtained using the
      PFOODR experimental technique. We demonstrate that the correct vibrational
      numbering and an improved RKR potential curve can be obtained by analyzing the
      experimental term values in combination with all observed bound-free and discrete
      spectra. Finally, term values for four 6Li2 3(3)Pig ro-vibrational levels were
      obtained using PFOODR spectroscopy. The measured isotope shifts confirm the
      absolute vibrational numbering obtained from the present analysis. Copyright 1999
      Academic Press.

PMID- 10079150
TI  - The NO Dimer.
AB  - Spectra of the symmetric nu1 vibration of the NO dimer have been recorded in gas
      phase at low temperature, with a high-resolution infrared Fourier transform
      spectrometer. All the lines were least-squares fitted to a Voigt profile
      convoluted with the well-known apparatus function of the spectrometer. By means
      of this method, the frequencies of more than 109 new lines were measured. From
      the intensities of a set of 33 well-fitted and completely isolated lines, the
      transition moment was extracted. NO-broadening coefficients of the dimer lines
      were also measured as well as the predissociation time, which was found to be
      (2.65 +/- 0.53) ns. Copyright 1999 Academic Press.

PMID- 10079151
TI  - Laser-Desorption Supersonic Jet Spectroscopy of Phthalocyanines.
AB  - The laser-induced fluorescence excitation spectra of zinc phthalocyanine,
      chloroaluminum phthalocyanine, magnesium phthalocyanine, and free-base
      phthalocyanine have been investigated under jet-cooled conditions, by using
      pulsed infrared laser desorption as the means of vaporization. Assignment of the
      observed vibronic transitions reveals that many of them gain intensity from
      coupling of the S1(Q) state with the S2(B) and Q' states. Low-frequency out-of
      plane modes of the macrocycle are observed in the region below 100 cm-1; the
      vibronic structure in this region of the spectrum is sensitive to deviation of
      the molecule from a planar geometry. The S1-S0 excitation energy shows a weak
      dependence on the hole size of the macrocycle. Copyright 1999 Academic Press.

PMID- 10079152
TI  - Linestrengths of Torsion-Rotation Transitions of Methanol for J </= 22, K </= 14,
      and upsilont </= 2 from Hamiltonian-Based Calculations.
AB  - Linestrengths have been obtained for methanol based on matrix elements of the
      dipole moment operator evaluated in a set of torsion-rotation eigenfunctions. The
      latter were obtained from the parameters and effective Hamiltonian giving the
      best spectral fit available for a data set containing J </= 20, K </= 14, and
      upsilont </= 1 microwave and far infrared transitions. The dipole moment function
      was represented as a Fourier expansion in the torsional angle gamma. Values for
      the permanent components ua and ub were obtained from experiment; values for
      their cos 3gamma variation and for the sin 3gamma variation of uc were obtained
      from quantum chemistry molecular orbital calculations. The approach described
      allows calculation of the linestrength for any transition which satisfies the
      general selection rule A1 left and right arrow A2 or E left and right arrow E. A
      complete set of such linestrengths for all methanol torsion-rotation transitions
      involving levels with J </= 22, K </= 14, and upsilont </= 2, and with
      intensities and frequencies above the rather small cutoff limits of 10(-6) D2 and
      1 kHz, respectively, together with individual contributions from the permanent
      and gamma-varying dipole moment components, have been tabulated and are available
      on request (ftp.monash.edu.au/pub/chem/1998a). Copyright 1999 Academic Press.

PMID- 10079153
TI  - A New Expression for Multidimensional Franck-Condon Integrals.
AB  - A new closed form expression for the Franck-Condon integrals for overlap between
      arbitrary multidimensional harmonic oscillators has been exactly derived by
      employing the generating functions method. The calculations lead to the deduction
      of some general rules whereby an arbitrary multidimensional Franck-Condon
      integral can be expressed as sums of products of the Hermite polynomials.
      Copyright 1999 Academic Press.

PMID- 10079154
TI  - The High-Resolution Raman Spectrum of the nu4 Band of Diborane.
AB  - The high-resolution Raman spectra of the nu4 bands of 11B2H6 and 11B10BH6 have
      been recorded and analyzed. The recordings have been made using a high-resolution
      spectrometer based on the inverse Raman effect. Q branches have been observed,
      but P and R branches were too weak to be seen, and simulations of the observed
      band contour have been necessary to complete the analysis. A weak Coriolis
      resonance with the 2nu10 level is present in the 11B2H6 spectrum. The band
      centers obtained are 790.9829(12) and 804.76985(27) cm-1 for 11B2H6 and 10B11BH6,
      respectively (uncertainties are type A with a coverage factor k = 1, i.e., 1
      standard deviation). Copyright 1999 Academic Press.

PMID- 10079155
TI  - Improved Parameterization for Combined Isotopomer Analysis of Diatomic Spectra
      and Its Application to HF and DF.
AB  - A new way of representing vibration-rotation term values for multiple isotopomers
      of a given electronic state of a diatomic molecule is presented which resolves
      problems associated with the way the conventional combined isotopomer expansion
      represents the atomic mass-dependent JWKB and Born-Oppenheimer breakdown
      correction terms. Its application to infrared and microwave data for HF and DF
      yields new Dunham expansion coefficients and Born-Oppenheimer breakdown
      correction terms for this species. This procedure is implemented in a generally
      available computer program for fitting to various types of data involving one or
      several electronic states of multiple isotopomers of a diatomic molecule.
      Copyright 1999 Academic Press.

PMID- 10079156
TI  - FTIR Emission Spectra, Molecular Constants, and Potential Curve of Ground State
      GeO.
AB  - Extensive new high-temperature, high-resolution FTIR emission spectroscopy
      measurements for the five common isotopomers of GeO are combined with previous
      diode laser and microwave measurements in combined isotopomer analyses. New
      Dunham expansion parameters and an accurate analytical potential energy function
      are determined for the ground X1Sigma+ state. Copyright 1999 Academic Press.

PMID- 10079157
TI  - Analysis of High-Resolution FTIR Spectrum of the nu6 Band of H13COOH.
AB  - The FTIR spectrum of the nu6 band of H13COOH has been collected at a resolution
      of 0.004 cm-1 in the frequency range of 1030-1160 cm-1. The nu6 band was analyzed
      to be an A-B hybrid band and perturbed by the nearby nu8 band through a-, and b
      Coriolis coupling terms. Using a Watson's A-reduced Hamiltonian in the Ir
      representation, with the inclusion of a- and b-Coriolis resonances, a total of
      3004 IR transitions of nu6 have been analyzed to provide rovibrational constants
      for the v6 = 1 state with a standard deviation of 0.00047 cm-1. The nu6 band was
      found to be centered at 1095.40365 +/- 0.00003 cm-1. Copyright 1999 Academic
      Press.

PMID- 10079158
TI  - Absolute Intensities of the Infrared Bands of Gaseous Acrylonitrile.
AB  - Laboratory spectral data (peak positions and integrated band intensities) of the
      infrared bands of acrylonitrile (CH2CHCN) gas in the region 4000-220 cm-1 are
      presented. Even though CH2CHCN has not yet been identified in Titan's atmosphere,
      it is among the possible photochemical and cosmic irradiation products of CH4 +
      N2 chemistry in the atmosphere of Titan. Laboratory simulations of Titan's
      atmospheric chemistry also give CH2CHCN as a product species. The results of our
      evaluation of the infrared intensity data provide an upper limit of the
      stratospheric abundance of CH2CHCN. Copyright 1999 Academic Press.

PMID- 10079159
TI  - Vibronic Emission Spectrum of p-Xylyl Radical.
AB  - We have obtained high-resolution Fourier transform emission spectra of the A left
      and right arrow &Xtilde; transition of the jet-cooled p-xylyl radical in the 450
      nm spectral region. The band contours of several vibronic bands are examined. By
      using the rotational constants obtained from previous high-resolution LIF spectra
      and information about the torsional constants from dispersed fluorescence
      experiments, both a-type and b-type band contours are simulated. Based on
      symmetry arguments and the results of the simulation, we have reassigned the 6a
      and 6b vibrational mode frequencies of the ground electronic state of the p-xylyl
      radical. Copyright 1999 Academic Press.

PMID- 10079160
TI  - High-Resolution, Rotationally Resolved Electronic Spectroscopy of the MgNC
      Radical.
AB  - High-resolution, rotationally resolved, laser-induced fluorescence (LIF) spectra
      for the origin band, as well as several transitions involving vibrationally
      excited levels of the A2Pi <-- &Xtilde2Sigma+ electronic transition of the MgNC
      radical, have been recorded using the output of a pulse-amplified Ti:Sapphire
      ring laser. The MgNC radical was generated in a supersonic free jet expansion by
      simultaneous laser ablation of a magnesium rod and photolysis of acetonitrile
      (CH3CN). Rotational analysis yielded molecular constants for both the ground and
      excited states of the studied vibronic transitions. The molecular constants for
      the vibrationless state of the &Xtilde state are in excellent agreement with
      previous microwave studies of MgNC. Since the A electronic state of MgNC is a
      linear 2Pi state, the bending vibronic level structure is subject to both Renner
      Teller and spin-orbit coupling. Suggested vibronic assignments of the observed
      transitions, made considering both these interactions and with the aid of the
      rotational analysis, are discussed. Copyright 1999 Academic Press.

PMID- 10079161
TI  - The Far Infrared Spectrum of the NO Dimer.
AB  - The far-infrared spectrum of the NO dimer in the gas phase has been observed for
      the first time using a long-path (180 m) cooled (99 K) absorption cell and a
      Bomem Fourier transform spectrometer. Four weak vibration-rotation bands were
      detected in the 120-450 cm-1 region and assigned to intermolecular vibrations of
      the cis-planar ON-NO complex. The strongest is a type b band at 239.36 cm-1,
      which is assigned as the nu2 (symmetric bending) fundamental. A second type b
      band at 134.50 cm-1, partly obscured by 2Pi3/2 <-- 2Pi1/2 transitions of the NO
      monomer, is assigned as the nu3 (intermolecular stretch) fundamental. A third
      type b band at 351.38 cm-1 can then be assigned as the nu2 + nu3 combination
      band. Finally, a very weak type a band at 429.14 cm-1 is assigned as the nu6
      (antisymmetric bending) fundamental. We report here detailed analyses of the nu2
      and nu2 + nu3 bands, which yielded upper state rotational parameters, centrifugal
      distortion parameters, and band origins. Somewhat less extensive analyses for nu3
      and nu6 give their rotational parameters and band origins. These results resolve
      the mystery of the true values of the intermolecular vibrational frequencies of
      the NO dimer, which turn out to be rather different from previous determinations
      based on condensed phase spectra. Copyright 1999 Academic Press.

PMID- 10079162
TI  - High-Resolution Infrared Spectra in the C-H Region of CH2F2: The nu6 and 2nu2
      Bands.
AB  - High-resolution, infrared absorption spectra of the nu6 (asymmetric C-H stretch)
      and 2nu2 (H-C-H symmetric bend overtone) bands of jet-cooled CH2F2 are reported
      with a sub-Doppler resolution of approximately 0.002 cm-1. More than 600
      transitions were observed in the range of 3002-3036 cm-1, of which 268 were
      assigned the nu6 fundamental and 184 were assigned to the 2nu2 overtone. A fit of
      the nu6 band to the A-reduced Watson Hamiltonian yielded eight effective
      constants including nu0 = 3014.0503(1), A' = 1.62868(4), B' = 0.354165(5), and C'
      = 0.308852(3) cm-1. Similarly, the weaker 2nu2 band was fit to seven parameters
      including nu0 = 3026.2297(2), and A' = 1.63396(6), B' = 0.35367(1), and C' =
      0.31183(1) cm-1. Numbers in parentheses are two standard deviations in units of
      the last digit. Anomalous values of the A rotational constant and the DeltaK
      centrifugal distortion constant are attributed to an a-axis Coriolis interaction
      between the 2nu2 and nu6 bands. The relative intensity of the 2nu2 band is used
      to estimate the stretch-bend anharmonic interaction with nu1. Copyright 1999
      Academic Press.

PMID- 10079163
TI  - The Vacuum Ultraviolet Absorption Bands of the Pink Afterglow Spectrum of
      Molecular Nitrogen Revisited at High Resolution.
AB  - The absorption spectrum of the pink afterglow of molecular nitrogen in the vacuum
      ultraviolet has been analyzed at high resolution. The spectrum exhibits hot bands
      involving vibrational levels of the electronic ground state as high as v" = 19.
      Experimentally determined term values are derived for v" = 0-19, of which v" = 16
      19 were before now poorly known. Copyright 1999 Academic Press.

PMID- 10079164
TI  - The b1Sigma+(b0(+)) --> X3Sigma-(X10(+), X21) and a1Delta(a2) --> X21 Transitions
      of AsI.
AB  - Emission spectra of the b1Sigma+(b0(+)) --> X3Sigma-(X10(+), X21) and a1Delta(a2)
      --> X21 transitions of AsI have been measured in the near-infrared spectral
      region with a Fourier-transform spectrometer. The arsenic iodide radicals were
      generated and excited in a fast-flow system by reaction of arsenic vapor (Asx)
      with iodine and microwave-discharged oxygen. The most prominent features in the
      spectrum are six band sequences of the strong b1Sigma+(b0(+)) --> X3Sigma
      (X10(+)) transition in the range 800-900 nm. With much lower intensities the
      hitherto unknown b1Sigma+(b0(+)) --> X3Sigma-(X21) subsystem and the a1Delta(a2) 
      -> X21 transition near 1660 nm are observed. Vibrational analyses have yielded
      improved molecular constants for the X10(+) and b0(+) states and first values of
      the electronic energies and vibrational constants of the X21 and a2 states (in cm
      1), X21: Te = 289.8(2), omegae = 255.2(2), omegaexe = 0.68(7), a2: Te =
      6305.4(3), omegae = 267.8(1), omegaexe = 0.56(2), where the numbers in
      parentheses are the standard deviations of the parameters. Copyright 1999
      Academic Press.

PMID- 10079165
TI  - Allene nu9 and nu10: Low-Temperature Measurements of Line Intensity.
AB  - We report laboratory intensity measurements for the weak nu9 (998.8 cm-1) and
      intense nu10 (841.1 cm-1) bands of allene. Allene is predicted to be a
      constituent of Titan's atmosphere, and measurements of its abundance would yield
      important information about the atmospheric chemistry of that body. Spectra were
      obtained at a temperature of 200 K (approximating Titan conditions) using the
      high-resolution FTS instrument at Kitt-Peak National Observatory's McMath-Pierce
      observatory. A total of 505 nu9 and 687 nu10 line intensities were fit using a
      least-squares method to accurately determine two sets of transition dipole
      moments. Integrated band intensities computed utilizing the fitted parameters
      were found to be 36 +/- 4% cm-2 atm-1 and 301 +/- 4% cm-2 atm-1 for nu9 and nu10,
      respectively, at 200 K. Copyright 1999 Academic Press.

PMID- 10079166
TI  - Oxygen Broadening of Acetylene Lines in the nu5 Band at Low Temperature.
AB  - O2-broadening coefficients have been measured for 29 lines of C2H2 at 173.2 K in
      the P and R branches of the nu5 band near 14 um, using a tunable diode-laser
      spectrometer. The collisional widths obtained by Rautian profiles closely fitting
      the measured spectral shape of the lines are slightly larger than those derived
      from Voigt profiles. The broadening coefficients are compared with results
      calculated from a semiclassical theory, performed by considering, in addition to
      electrostatic interactions involving the hexadecapole moments of C2H2 and O2, the
      atom-atom Lennard-Jones model. By comparing broadening coefficients at 297 and
      173.2 K from a simple power law, the temperature dependence of these broadenings
      has been determined both experimentally and theoretically. Copyright 1999
      Academic Press.

PMID- 10079167
TI  - Gas-Phase Raman Spectrum of NO Dimer.

PMID- 10079168
TI  - Perturbations in the Infrared Spectrum of the HCCH-CO Complex: The CO Stretching
      Region.

PMID- 10079169
TI  - Tunable Far-Infrared Spectroscopy of HF, H35Cl, and H37Cl in the 6 to 9 THz
      Region.

PMID- 10079172
TI  - Regulation of pyruvate kinase M gene expression.

PMID- 10079173
TI  - Analysis of the RNA recognition motifs of human neuronal ELAV-like proteins in
      binding to a cytokine mRNA.
AB  - Human neuronal Elav-like proteins contain three RNP-type RNA recognition motifs
      (RRMs). Previous reports demonstrated that a single RRM of the proteins is not
      sufficient to bind to the uridine-rich stretch in the 3' untranslated region of
      mRNAs and that the bi-RRM peptide consisting of the first two RRMs is necessary
      for the binding. The present study was designed to examine the potential
      contributions of the first two RRMs when binding to a cytokine mRNA. Deletions of
      the internal or terminal amino acid residues of the first RRM (RRM1) of the
      HuC/ple21 ELAV-like protein completely abolished RNA binding. However, removal of
      any region of the second RRM (RRM2) except for the eight amino acid residues,
      which correspond to the potent fourth beta-sheet structure of RRM2, did not
      affect RNA binding. Conjugation of the eight amino acid residues to RRM1 enhanced
      the RNA binding as well as the entire RRM2, indicating that the octapeptide of
      RRM2 can be compensated for by the binding function of RRM2. The present study
      also showed that the substitutions of glutamic acid at 42 for aspartic acid and
      leucine at 44 for phenylalanine in the first potent alpha-helix structure of
      RRM1, as were seen in another ELAV-like protein Hel-N1, markedly affected the RNA
      binding.

PMID- 10079174
TI  - The lipoxygenase product 13-hydroxyoctadecadienoic acid (13-HODE) is a selective
      inhibitor of classical PKC isoenzymes.
AB  - 13-Hydroxyoctadecadienoic acid (13-HODE), hydroxylinoleic acid, is a major
      lipoxygenase metabolite which is produced by myeloid inflammatory cells and
      modifies inflammatory cell activity. The biological effects of 13-HODE in non
      haemopoietic cells (HUVEC) have been attributed to the incorporation of 13-HODE
      into 13-HODE containing diacylglycerol and the selective inhibition of protein
      kinase C. Our studies, using whole promyeloid cells (HL60) and recombinant PKC
      isoenzymes in an in vitro assay, showed that 13-HODE inhibited PKC-alpha, beta1,
      and PKC-betall, but did not affect the activity of PKC-delta. These data suggest
      that the actions of hydroxylinoleic acid on myeloid cells include the selective
      inhibition of classical PKC isoenzymes.

PMID- 10079175
TI  - Effects of cytosolic Ca2+ on membrane voltage and conductance of cultured
      mesangial cells from stroke-prone spontaneously hypertensive rats and WKY rats.
AB  - Mesangial cells (MC) are considered to play an important role in the development
      of hypertension. The purpose of this study was to characterize the effects of
      cytosolic Ca2+ on membrane voltage and conductance of MC using stroke-prone
      spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). We applied
      the patch-clamp technique in the whole-cell configuration to measure membrane
      potential (Vm) and ion currents. There was no significant difference in resting
      Vm values between MC from WKY and SHRSP. The cytosolic Ca2+ increase induced
      membrane depolarization and the increase of Cl- currents in MC from WKY but not
      in MC from SHRSP. On the other hand, the Ca2+ increase induced membrane
      hyperpolarization and the increase of K+ currents in MC from SHRSP but not in MC
      from WKY. Such differences between MC from two rat strains may play an important
      role in the alterations in renal hemodynamics observed in hypertension.

PMID- 10079176
TI  - Appropriately spaced nuclear localizing signals are necessary for efficient
      nuclear import of nonnuclear proteins.
AB  - To deliver nonnuclear proteins into the nucleus, we have examined the locations
      and number of nuclear localizing signals by use of simian virus 40 large T
      antigen (SV40Ta) and yeast enhanced green fluorescent protein (yEGFP) in
      Saccharomyces cerevisiae as a model system. When only one SV40Ta was added to
      either the N- or C-terminus of yEGFP, the fluorescence of yEGFP was detected in
      both the nucleus and the cytoplasm. When two SV40Ta signals were added, one to
      the N-terminus and one to the C-terminus of yEGFP (SV40Ta-yEGFP-SV40Ta), the
      fluorescence of yEGFP was localized in only the nucleus. When the presequence of
      cytochrome oxidase subunit IV (pCOXIV) was inserted between the SV40Ta and the N
      terminus of yEGFP (SV40Ta-pCOXIV-yEGFP-SV40Ta) in this construct, the
      fluorescence was located in both the nucleus and the cytoplasm, suggesting that
      the increased distance between the two SV40Ta signals decreased the efficiency of
      transport into the nucleus. When an additional SV40Ta signal was inserted between
      pCOXIV and yEGFP (SV40Ta-pCOXIV-SV40Ta-yEGFP), the fluorescence was localized
      only in the nucleus, indicating that two SV40Ta signals spaced by pCOXIV of 28
      amino acid residues forming an alpha-helix are potent in transporting yEGFP into
      the nucleus. These results indicate that two SV40Ta signals spaced appropriately
      are essential for the efficient transport of the nonnuclear protein into the
      nucleus.

PMID- 10079177
TI  - Low intensity pulsed ultrasound exposure increases prostaglandin E2 production
      via the induction of cyclooxygenase-2 mRNA in mouse osteoblasts.
AB  - Both prostaglandin E2 (PGE2) and low intensity pulsed ultrasound (U/S) exposure
      have been reported to accelerate fracture repair. We hypothesized that these two
      pathways are interactive. To verify this hypothesis, we examined the regulation
      of PGE2 production by U/S exposure (sine wave of 1.5MHz repeating at 1kHz,
      30mW/cm2, 20 minutes) in mouse osteoblastic cell line, MC3T3-E1. The production
      of PGE2 in osteoblasts was augmented by U/S, which was threefold at 60 min. in
      comparison with unexposed samples. Then we evaluated the expression of
      cyclooxygenase-2 (COX-2) mRNA, which is a critical enzyme for PGE2 production.
      U/S rapidly up-regulated the expression of COX-2 mRNA in a time dependent manner.
      In addition, PGE2 production by U/S was drastically suppressed by a selective
      inhibitor of COX-2. These results provide strong evidence that PGE2 production in
      osteoblasts is dependent upon the induction of COX-2 mRNA expression by U/S and
      offer a mechanistic insight into how U/S accelerates fracture repair.

PMID- 10079178
TI  - Single-molecule electron tunneling spectroscopy of the higher plant light
      harvesting complex LHC II.
AB  - Electronic spectroscopy of a single biological molecule is demonstrated with
      approximately 4 A spatial resolution. The light-harvesting complex II (LHC II),
      in the ground and photo-excited states, was studied using scanning tunneling
      microscopy and spectroscopy of intact Photosystem II complexes. Analysis of the
      spectra indicates that the main mechanisms of tunneling between the STM tip and
      the surface involve delocalized electronic states of the LHC II and local
      vibronic states associated with C=C, C=O, C-H, N-H, and O-H groups near the LHC
      II surface. Conduction within the bulk LHC II is then due to ohmic and hopping
      conduction as well as tunneling between amino acid residues. Light activation of
      LHC II occurs via a photoconductive rather than a photovoltaic mechanism. There
      is a dramatic light-induced increase in the electronic density of states
      indicating a light-induced enhancement of energy and electron delocalization
      which is important for the efficient and rapid transfer of excitation energy from
      LHC II to the Photosystem II reaction center.

PMID- 10079179
TI  - Active oxygen species in blue light mediated signal transduction in coleoptile
      tips.
AB  - Coleoptile tip is a blue-light sensitive tissue possessing a "blue light
      receptor" which, upon activation, elicits a signal cascade resulting in
      phototropic curvature of the coleoptile. In this context, the nature of the
      photoreceptors and the exact mechanism through which the photoreceptors
      transduces the signal across the membrane are not clear. In this study, we
      attempted to examine whether the blue light receptor perturbs redox status of the
      coleoptile tip and sensitizes molecular oxygen as part of the signal reactions.
      Coleoptile tips of Sorghum bicolor and wheat (Triticum vulgare) grown in the dark
      showed pronounced ascorbate free radical signal, which diminished upon
      illumination with weak blue light for one minute. Concomitantly, the generation
      of superoxide radical by the coleoptile tip was augmented upon illumination with
      blue light. Various thiol blockers tested in this study caused powerful
      inhibition of blue light induced superoxide anion radical generation. Treatment
      with these thiol blockers, with the exception of NEM, resulted in marked increase
      in the levels of ascorbic acid free radical in the blue light irradiated
      coleoptiles. The blue light stimulated O*-2-generation by the coleoptile tip
      homogenate is also inhibited by the inhibitors of blue light responses viz
      phenylacetic acid, potassium iodide, and sodium azide. Based on our observations,
      we postulate that the activated blue light receptor present in the coleoptile tip
      sensitizes molecular oxygen to superoxide anion radical in the tip initializing
      the blue light signal cascade reactions.

PMID- 10079180
TI  - Epithelin/granulin growth factors: extracellular cofactors for HIV-1 and HIV-2
      Tat proteins.
AB  - Epithelin/granulin growth factor is synthesized as a 593 amino acid precursor
      protein that contains 7.5 imperfectly conserved repeats of approximately 57 amino
      acids. Processed epithelin/granulin peptides have been isolated from
      vertebrate/invertebrate species and are growth factors implicated in epithelial
      and haemic cell function. Here they are identified as Human Immunodeficiency
      Virus (HIV) Tat binding proteins using the yeast two-hybrid assay.
      Intracellularly in yeast, mutation of selected cysteines in an epithelin/granulin
      dimeric repeat caused loss of binding to Tat exon 1. In vitro binding of HIV-1
      and HIV-2 Tat to epithelin/granulin dimeric and monomeric repeats was also
      observed by GST-glutathione bead "pulldown" assays. Because Tat is actively
      secreted from HIV-infected cells and has been shown to serve as a mitogenic
      factor for angiogenesis and for Kaposi-like cells, our observations suggest that
      epithelin/granulin growth factors may function as biologically important
      extracellular Tat co-factors.

PMID- 10079181
TI  - Recurrent missense (R197C) and nonsense (Y89X) mutations in the XLRS1 gene in
      families with X-linked retinoschisis.
AB  - Congenital retinoschisis (RS) is a hereditary eye disorder characterized by
      intraretinal schisis and central and peripheral retinal lesion. The gene
      responsible for the X-linked retinoschisis (XLRS1) has recently been isolated and
      found to contain mutations in affected members of several families. In this
      communication, two families with X-linked RS were analyzed for possible disease
      causing mutations by polymerase chain reaction amplification of exons followed by
      DNA sequencing. Our analyses reveal a missense mutation at codon 197 in exon 6
      and a nonsense mutation in exon-4 of XLRS1 gene. These changes resulted in the
      replacement of a highly conserved arginine by a cysteine residue and introduced a
      premature termination signal at codon 89, respectively. These mutations, which
      are transmitted through three generations, cosegregated with the disease, and are
      not found in the unaffected family members and 150 normal X-chromosomes, are
      likely to be pathogenic in these families.

PMID- 10079182
TI  - Sources of reactive oxygen species production in excitotoxin- stimulated
      cerebellar granule cells.
AB  - Reactive oxygen species (ROS) production in rat cerebellar granule cells in the
      presence of the excitotoxins N-methyl-d-aspartate (NMDA) and kainic acid (KA) and
      by the protein kinase C activator phorbol myristate acetate (PMA) was Ca2+
      dependent and resulted in decreased cell viability. Exposure of stimulated cells
      to rotenone (a respiratory chain inhibitor) did not decrease ROS levels and did
      not affect short-term cell viability. In cells stimulated by NMDA and KA,
      exposure to indomethacin (a cyclooxygenase inhibitor) and nialamide (a monoamine
      oxidase inhibitor) caused a decrease in ROS levels and increased cell viability
      occurred in NMDA-treated cells. In contrast, PMA-stimulated neurons did not show
      decreased ROS levels when exposed to indomethacin and nialamide. These studies
      suggest that there is a multiplicity of routes for Ca2+-dependent ROS production
      in neurons but that ROS generation by cyclooxygenase and monoamine oxidase is not
      controlled by protein kinase C.

PMID- 10079183
TI  - Human MD-1 homologue is a BCG-regulated gene product in monocytes: its
      identification by differential display.
AB  - BCG-CWS is a therapeutically potent immune activator which improves the prognosis
      of cancer patients. However, the targeting effector cells and molecules for BCG
      CWS in the human immune system have not been determined. Here, we found that BCG
      CWS activates human monocytes and concomitantly down-regulates expression of a
      human homologue of chicken MD-1 in the activated monocytes by differential
      display. According to a previous study, MD-1 forms a complex with the Toll family
      protein RP-105 on murine B cell lines to facilitate its stable expression. Thus,
      MD-1 may participate in regulation of innate immune activation on human
      monocytes. Our results, taken together with these recent findings regarding Toll
      family proteins, suggest that BCG-CWS acts on monocytes to modulate the human
      innate immune system via regulation of Toll family proteins.

PMID- 10079184
TI  - Two homologous cytochrome b5s are expressed in both neurons and glial cells of
      the rat brain.
AB  - To avoid the possibility of blood contamination and of gene rearrangement during
      library construction we isolated total RNA directly from cultured rat embryonic
      neuronal cells and glioma C6 cells to be used as template for RT-PCR. By using
      specific primers for both membrane-bound b5 and soluble b5, DNA bands of
      appropriate size were clearly amplified indicating that both neurons and glial
      cells expressed b5s, although soluble b5 seemed to be less expressed in these
      cells. Nucleotide sequence of the internal exon for soluble b5 was reinvestigated
      and confirmed to be 58 bp containing genetic codons for His-Ser-Ala-Leu and stop.

PMID- 10079185
TI  - Regulatory effect of thiamin pyrophosphate on pig heart pyruvate dehydrogenase
      complex.
AB  - The kinetic behavior of pig heart pyruvate dehydrogenase complex (PDC) containing
      bound endogenous thiamin pyrophosphate (TPP) was affected by exogenous TPP. In
      the absence of exogenous TPP, a lag phase of the PDC reaction was observed. TPP
      added to the PDC reaction medium containing Mg2+ led to a disappearance of the
      lag phase, inducing strong reduction of the Km value for pyruvate (from 76.7 to
      19.0 microM) but a more moderate decrease of Km for CoA (from 12.2 to 4.3 microM)
      and Km for NAD+ (from 70.2 to 33.6 microM), with no considerable change in the
      maximum reaction rate. Likewise, thiamin monophosphate (TMP) decreased the Km
      value of PDC for pyruvate, but to a lesser extent (from 76.7 to 57.9 microM) than
      TPP. At the unsaturating level of pyruvate, the A50 values for TPP and TMP were
      0.2 microM and 0.3 mM, respectively. This could mean that the effect of TPP on
      PDC was more specific. In addition, exogenous TPP changed the UV spectrum and
      lowered the fluorescence emission of the PDC containing bound endogenous TPP in
      its active sites. The data obtained suggest that TPP plays, in addition to its
      catalytic function, the important role of positive regulatory effector of pig
      heart PDC.

PMID- 10079186
TI  - Retinoic acid biosynthetic activity and retinoid receptors in the olfactory
      mucosa of adult mice.
AB  - Retinoids play important roles in the ontogenic development of the olfactory
      system in mammals, but their function in adult olfactory mucosa has not been
      explored. In the present study, the olfactory mucosal expression of nuclear
      retinoid receptors was examined in adult mice. Several retinoic acid receptor
      isotypes were identified in olfactory mucosa from adult C57BL/6 mice by RNA-PCR
      and DNA sequence analysis, including RARbeta, RXRalpha, RXRbeta, and RXRgamma. In
      addition, a previously unidentified mouse RXRbeta isoform containing a 12
      nucleotide insertion in exon 7 was detected. Furthermore, in vitro metabolic
      studies demonstrated that olfactory mucosal cytosolic and microsomal preparations
      are active in the biosynthesis of retinoic acids from all-trans- and 9-cis
      retinal. These results indicate that components of the retinoid signal
      transduction system are expressed in adult olfactory mucosa and may play
      important roles in gene regulation in this unique tissue where olfactory neuronal
      cells are continuously replaced.

PMID- 10079187
TI  - Sequence and tissue distribution of a novel G-protein-coupled receptor expressed
      prominently in human placenta.
AB  - We report here a novel gene, NPGPR, which encodes a G-protein-coupled receptor
      (GPCR) that is most similar to the peptide receptor subfamily. The coding region
      of the human NPGPR gene predicts a seven transmembrane domain receptor of 522
      amino acids and having a relatively large N-terminus of 147 amino acids. The
      NPGPR sequence has 30-33% amino acid identity to NPY receptors and similar
      percentage identity to orexin receptors (32%). Northern blot analysis reveals an
      abundant 1.5 kb NPGPR transcript in human placenta. Semi-quantitative RT-PCR
      determined additional sites of expression in thymus, testis and small intestine.
      These sites of mRNA expression suggest a potential role for the novel receptor in
      signaling to tissues undergoing active cell growth and differentiation. At low
      levels, NPGPR message is detectable in several other tissues including spleen,
      prostate, brain, heart, ovary, colon, kidney, lung, liver, and pancreas.

PMID- 10079188
TI  - High affinity interaction of endothelin-3 with recombinant ETA receptors.
AB  - Pharmacological evidence has suggested that endothelin-3 (ET-3) may act via a
      novel form of ET receptor that is shared by ETA receptor antagonists but not by
      ETB receptor selective agonists. This study analyses the properties of
      interaction of ET-3 with recombinant bovine ETA receptor. Apparent Kd(ET-3)
      values as low as 50 nM were defined from [125I]ET-1 binding experiments performed
      at low (5 microg/ml) protein concentrations in the assays. Larger (up to 1
      microM) values were artefactually obtained in experiments performed at larger
      protein concentrations. The three monoiodo ET-3 derivatives were synthetized.
      ([125I]Y14)ET-3 did not recognize ETA receptors. ([125I]Y6)ET-3 labelled 18% of
      [125I]ET-1 binding sites with a Kd value of 320 pM. ([125I]Y13)ET-3 labelled 44%
      of [125I]ET-1 binding sites with a Kd value of 130 pM. High affinity ([125I]Y6)ET
      3 and ([125I]Y13)ET-3 bindings were prevented by ET-1 (Kd = 5-7 pM), ET-3 (Kd =
      70-250 pM), BQ-123 (Kd = 2 nM) and FR139317 (Kd = 2 nM) but not by low
      concentrations of 4-AlaET-1, sarafotoxin S6c or IRL1620. The three monoiodo ET-3
      derivatives bound to recombinant rat ETB receptors with a pM affinity. The
      results suggest that ET-3, ([125I]Y6)ET-3 and ([125I]Y13)ET-3 should not be
      considered as ETB receptor specific ligands.

PMID- 10079189
TI  - Rapid aggregate formation of the huntingtin N-terminal fragment carrying an
      expanded polyglutamine tract.
AB  - Huntington's disease (HD) is caused by an expansion of the CAG repeat in the HD
      gene. The repeat is translated to the polyglutamine tract as huntingtin, the
      product of HD gene. Several studies showed that the expansion of polyglutamine
      tract leads to formation of cytoplasminc and/or intranuclear aggregates in vivo
      or in vitro. To understand the molecular mechanism of the aggregate formation, we
      studied the transient expression of HD exon 1-GFP fusion proteins in COS-7 cells.
      The fusion protein carrying 77 glutamine repeats aggregated in a time-dependent
      manner, while the fusion protein carrying 25 glutamine tract remained to be
      distributed diffusely in the cytoplasm even 72 hours after transfection.
      Initially, fluorescent signals were diffusely distributed in the COS-7 cells that
      were transfected with the construct containing the 77 CAG repeats. Approximately
      40 hours later after the transfection, large aggregates grew very rapidly in
      those cells and the diffuse cytoplasmic fluorescence faded out. This process was
      completed within 40 minutes from the appearance of small aggregates in the
      perinuclear regions. The addition of cycloheximide reduced the frequencies of
      aggregate formation. A possibility was discussed that the aggregate formation was
      via nucleation. The focal concentration of mutated proteins in neurons may
      trigger the aggregate formation.

PMID- 10079190
TI  - Cross-linking between cytochrome c3 and flavodoxin from Desulfovibrio gigas.
AB  - Tetraheme cytochrome c3 (13 kDa) and flavodoxin (16 kDa), are small electron
      transfer proteins that have been used to mimic, in vitro, part of the electron
      transfer chain that operates between substract electron donors and respiratory
      electron acceptors partners in Desulfovibrio species (Palma, N., Moura, I.,
      LeGall, J., Van Beeumen, J., Wampler, J., Moura, J. J. G. (1994) Biochemistry 33,
      6394-6407). The electron transfer between these two proteins is believed to occur
      through the formation of a specific complex where electrostatic interaction is
      the main driving force (Stewart, D., LeGall, J., Moura, I., Moura, J.J.G., Peck,
      H.D., Xavier, A.V., Weiner, P.K. and Wampler, J.E. (1988) Biochemistry 27, 2444
      2450, Stewart, D., LeGall, J., Moura, I., Moura, J.J.G., Peck, H.D., Xavier,
      A.V., Weiner, P., Wampler, J. (1989) Eur. J. Biochem. 185, 695-700). In order to
      obtain structural information of the pre-complex, a covalent complex between the
      two proteins was prepared. A water-soluble carbodiimide [EDC (1-ethyl-3(3
      dimethylaminopropyl) carbodiimide hydrochloride] was used for the cross linking
      reaction. The reaction was optimized varying a wide number of experimental
      parameters such as ionic strength, protein and cross linker concentration, and
      utilization of different cross linkers and reaction time between the crosslinker
      and proteins.

PMID- 10079191
TI  - Neuronal differentiation of neuro 2a cells by inhibitors of cell cycle
      progression, trichostatin A and butyrolactone I.
AB  - Trichostatin A (TSA, 17 nM), a specific and reversible inhibitor of histone
      deacetylase induced neurite network formation at and after 4 days. The networks
      were preserved for at least 3 weeks in the presence of TSA. Butyrolactone I (BLI,
      23.6 microM), an inhibitor of cdc2 and cdk2 kinases, also induced neurite
      extension. Both compounds enhanced the acetylcholinesterase activity of the
      cells. Cell cycle progression of the cells was blocked by TSA (17 nM) at G1 phase
      alone. Furthermore, the level of histone hyperacetylation and p21(WAF1)
      expression in TSA-treated cells increased transiently. These findings suggest
      that the induction of the neuronal differentiation in Neuro 2a cells by these
      agents requires the cell cycle arrest at G1 phase, which is caused by inhibition
      of cycline dependent kinase, a target molecule of BLI and p21(WAF1).

PMID- 10079192
TI  - Brain regional distribution of endocannabinoids: implications for their
      biosynthesis and biological function.
AB  - The amounts, in nine different rat brain regions, of the two endocannabinoids,
      anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG), and
      of the putative AEA precursor N-arachidonoyl-phosphatidylethanolamine (NArPE),
      were determined by isotope-dilution gas chromatography-mass spectrometry and
      compared to the number of cannabinoid binding sites in each region. The
      distribution of NArPE, reported here for the first time, exhibited a good
      correlation with that of AEA, the former metabolite being 3-13 times more
      abundant than the endocannabinoid in all regions. The highest amounts of both
      metabolites (up to 358.5 and 87 pmol/g wet weight tissue, respectively) were
      found in the brainstem and striatum, and the lowest in the diencephalon, cortex,
      and cerebellum. These data support the hypothesis that, in the brain, AEA is a
      metabolic product of NArPE and may reach levels compatible with its proposed
      neuromodulatory function. The brain distribution of 2-AG, also described in this
      study for the first time, was found to correlate with that of AEA with levels
      ranging from 2.0 to 14.0 nmol/g (in the diencephalon and brainstem,
      respectively). The distribution of the endocannabinoids did not match exactly
      with that of cannabinoid binding sites, suggesting either that these compounds
      are not necessarily produced near their molecular targets, or that they play
      functional roles additional to the activation of cannabinoid receptors. Regional
      differences in the ligand/receptor ratios may also lead to predict corresponding
      differences in the efficiency of receptor activation, as shown by previous
      studies.

PMID- 10079193
TI  - Changes in caspase expression in Alzheimer's disease: comparison with development
      and aging.
AB  - Changes in caspase-2 and -3 protein levels in Alzheimer's disease (AD) brains
      were assessed in comparison with their expression in development and aging. The
      protein levels of caspase-2 and -3 were significantly increased in AD brains,
      caspase-2 in the particulate fraction and caspase-3 in both the cytosolic and
      particulate fractions, compared with controls. Immunoblot analysis of brain
      extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that
      caspase-3 levels were high from E19 to 2 weeks, while caspase-2 remained high
      from 4 to 96 weeks, indicating that the expression of caspase-2 and -3 is
      differentially regulated during development and aging. These results suggest that
      caspase-2 and -3 are upregulated in AD and that the changes in AD are different
      from those observed in senescent brains.

PMID- 10079194
TI  - Ribosome-associated protein LBP/p40 binds to S21 protein of 40S ribosome:
      analysis using a yeast two-hybrid system.
AB  - The ribosome-associated protein LBP/p40, which was originally named after
      "laminin binding protein precursor p40," is distributed on the cell surface as
      laminin binding protein p67 (LBP/p67), in the nucleus, and on 40S ribosomes. In a
      broad range of eukaryotes, the localization of LBP/p40 on the 40S ribosome is
      well conserved. Two yeast homologs of LBP/p40 are believed to be essential for
      cell viability and each gene product probably corresponds to the assembly and/or
      stability of the 40S ribosomal subunit. The precise role of LBP/p40 in
      translation, however, remains to be elucidated, especially in higher eukaryotes.
      In this report, we used a yeast two-hybrid screening method to isolate molecules
      associated with human LBP/p40 protein on ribosomes. We found that the 40S
      ribosomal protein S21 was tightly bound with LBP/p40 in this yeast two-hybrid
      system and in in vitro analysis. Further, we discovered that the association
      required a broad region of the LBP/p40 amino acid sequence, which corresponds to
      the highly conserved region of LBP/p40 homologs among eukaryotes.

PMID- 10079195
TI  - Structure and expression of the murine thromboxane A2 receptor gene.
AB  - The gene encoding the murine thromboxane A2 receptor (TP) is split into three
      exons and spans 6.2 kilobase pairs. Primer extension analysis revealed two
      transcription initiation sites located approximately 210 nucleotides 5' of the
      first intron. The 1.2-kb 5'-flanking region lacks typical TATA and CAAT boxes but
      contains several potential regulatory elements including binding sites for Sp-1,
      NF-kappaB, AP-2, and a glucocorticoid response element. A 192-bp murine
      repetitive B2 element is located in the 5'-flanking region, but did not exert a
      negative effect on the basal promoter activity in transient transfection
      experiments with reporter constructs. Ribonuclease protection assays showed
      expression of TP RNA in several organs including thymus, spleen, kidney, and
      lung. In the thymus, in situ hybridization revealed transcripts in the cortex,
      but not in the medulla, suggesting that thromboxane A2 may play a role in the
      development of T-lymphocytes.

PMID- 10079196
TI  - Activation of nitric oxide synthase (NOS3) by mechanical activity alters
      contractile activity in a Ca2+-independent manner in cardiac myocytes: role of
      troponin I phosphorylation.
AB  - Cardiac myocytes express the calcium-responsive nitric oxide synthase (eNOS or
      NOS3). Activation of NOS3 by increased intracellular Ca2+ concentration, [Ca2+]i,
      has been demonstrated to decrease myocyte contractile responsiveness, although
      this appears to occur in a Ca2+-independent manner. Therefore, the aim of this
      study was to examine the possibility that contractile activity could be modulated
      by an NO-mediated alteration in the phosphorylation status of troponin I, which
      is known to alter myofilament sensitivity to Ca2+. During pacing at 3 Hz, 32P
      labeled myocytes exhibited a 59 +/- 9% increase in TnI phosphorylation compared
      to quiescent cells (p < 0.05), an effect that was significantly attenuated by
      either methylene blue or l-nitroarginine (l-NA). While exposure to methylene blue
      significantly increased the contractile amplitude of paced myocytes, this was not
      accompanied by an alteration in intracellular Ca2+. These data indicate that the
      NO-mediated effects on myocyte contraction may be elicited through an alteration
      in myofilament Ca2+ sensitivity that results from an alteration in the
      phosphorylation status of troponin I.

PMID- 10079197
TI  - The long isoform of the cell adhesion molecule C-CAM binds to actin.
AB  - C-CAM is a member of the carcinoembryonic antigen family (CEA) of the rat, which
      mediates cell adhesion in vitro and binds to signal transduction molecules. In
      many tissues C-CAM is expressed in the apical domain of the plasma membrane in
      close contact with intracellular cortical microfilaments, e.g., in the microvilli
      of the brush borders of enterocytes. Regarding this subcellular localisation, we
      have investigated the C-CAM interaction with the cytoskeleton. The association of
      C-CAM with detergent-insoluble structures increased when the small intestinal
      mucosa was extracted under conditions known to preserve the cytoskeleton of the
      brush borders. We found a co-immunoprecipitation of actin with C-CAM of the small
      intestine mucosa which increased in the presence of the chemical cross-linker
      DSP, allowing the demonstration of complexes between C-CAM and actin of different
      molecular masses. A recombinant fusion protein of the cytoplasmic domain of the
      long isoform of C-CAM bound specifically to purified actin in a co-sedimentation
      assay. These results suggest an intrinsic actin-binding activity of C-CAM.

PMID- 10079198
TI  - Compilation and analysis of plant mitochondrial promoter sequences: An
      illustration of a divergent evolution between monocot and dicot mitochondria.
AB  - We have analyzed 67 sequences surrounding transcription initiation sites
      identified in higher plant mitochondria. The sequences were classified,
      independently for monocots and dicots, according to the presence of the CRTA core
      element found upstream of the first transcribed nucleotide and previously
      reported as an essential element of plant mitochondrial consensus promoters. This
      compilation provides new elements concerning the structure of consensus promoters
      and the relative importance of non-conserved promoters in plant mitochondria. It
      can be emphasized that promoter regions exhibit several differences between
      monocot and dicot mitochondria, presumably reflecting a divergent evolution: The
      sequences classified among consensus promoters as well as the distance between
      the first transcribed nucleotide and the core element are highly conserved in
      dicots while more plasticity is observed in monocots. It also appears that the
      proportion of promoters with neither the conserved promoter sequence nor any
      conserved motif is far greater in dicots than in monocots.

PMID- 10079199
TI  - Hydrazide synthesis: novel substrate specificity of amidase.
AB  - The amidase from Rhodococcus rhodochrous J1, which hydrolyses amide to acid and
      ammonia, was found to catalyze the synthesis of hydrazide using hydrazine as a
      substrate. This is the first report on the hydrazide synthesis through enzymatic
      reactions. The enzyme also acted on benzoic acid in the presence of hydrazine,
      yielding benzoic hydrazide. Together with the finding that benzoic hydrazide was
      converted into benzoic acid (when it was used as a substrate in the absence of
      hydrazine), these unique characteristics suggest that the reaction route for the
      formation of the acid from the hydrazide and that of the hydrazide from the acid
      are reversible to each other via the acyl-enzyme. Not only aromatic hydrazides
      but also aliphatic hydrazides were synthesized from the corresponding amides and
      hydrazine.

PMID- 10079200
TI  - Bone morphogenetic protein-3b (BMP-3b) gene expression is correlated with
      differentiation in rat calvarial osteoblasts.
AB  - BMP-3b (also called GDF-10) is a novel BMP-3-related protein recently discovered
      in rat femur tissue. Gene expression of BMP-3b in osteoblastic cells and its
      regulation by prolonged culture, BMP-2 and transforming growth factor beta1 (TGF
      beta1) were examined. The BMP-3b gene was highly expressed in rat osteoblasts
      obtained from calvarial bones but not in the osteoblastic cell lines (MC3T3-E1
      and U2-OS). BMP-3b mRNA increased during osteoblastic differentiation in
      prolonged culture and was associated with increased alkaline phosphatase (ALPase)
      activity. When BMP-2, an enhancer of ALPase activity, was added to the primary
      osteoblast culture, BMP-3b mRNA increased 6.9-fold after 24 h. In contrast, TGF
      beta1 treatment, which suppresses ALPase activity, rapidly and completely
      inhibited gene expression of BMP-3b. The regulation of BMP-3 mRNA differed from
      that of BMP-3b, even though both proteins share 81% identity. These findings
      indicate that BMP-3b gene expression is regulated by osteoblastic differentiation
      and BMP-3b functions in highly differentiated osteoblasts.

PMID- 10079201
TI  - Toward the engineering of a super efficient enzyme.
AB  - The catalytic activity of a mutant of Photobacterium leiognathi Cu, Zn superoxide
      dismutase in which the Glu59 residue, conserved in most bacterial variants of the
      enzyme, has been replaced by glutamine was investigated by pulse radiolysis. At
      neutral pH the enzyme was found to have a kcat/KM of 1.0 +/- 0.1 x 10(10) M-1s-1
      the highest value ever found for any superoxide dismutase. Brownian dynamics
      simulation suggests that such a high value is due to an enhanced substrate
      attraction by the modified electric field distribution. The mutant is also
      characterized by an active-site widely accessible for the solvent, since iodide
      is able to interact with the copper atom with an affinity constant twice as high
      as that found in the native enzyme. The large solvent accessible surface of the
      copper site together with a favorable distribution of the protein-generated
      electric field gives rise to the most efficient enzyme ever found with activity
      close to the diffusion limit.

PMID- 10079202
TI  - Human immunodeficiency virus-1 infection requires pertussis toxin sensitive G
      protein-coupled signalling and mediates cAMP downregulation.
AB  - The human immunodeficiency virus-1 (HIV-1) utilises CD4 and certain beta
      chemokine receptors, mainly CCR-5 and CXCR4, for attachment and virus entry into
      T-lymphocytes and monocytes/macrophages. CD4 and beta-chemokine receptors
      participate in intracellular signalling via protein tyrosine kinases and G
      protein-coupled signalling. The factors which influence HIV-1 replication and the
      intracellular signalling mechanisms elicited by the virus are not well
      understood. In this study, it was demonstrated that exposure of peripheral blood
      lymphocytes (PBLs) to a T-cell tropic strain of HIV-1 evokes signal(s) which
      results in downregulation of intracellular cAMP. In addition, pre-incubation of
      PBLs with the Gi-protein inhibitor Pertussis toxin mediated a significant
      inhibition of HIV-1 replication. These data strongly suggest that HIV-1 employs
      CD4 receptors and Gi-coupled proteins for entry into target cells and that
      productive HIV-1 infection is dependent on an active signalling event.

PMID- 10079203
TI  - Liver poly(ADP-ribose)polymerase is resistant to cleavage by caspases.
AB  - In hepatocytes the DNA repair enzyme poly(ADP-ribose)polymerase (PARP) is not
      proteolytically cleaved during apoptosis. The reason for this was investigated
      using a cell-free system that consisted of isolated nuclei from hepatocytes or
      thymocytes and cytosolic extracts from hepatocytes or thymocytes undergoing
      apoptosis. It was found that liver PARP is resistant to proteolytic cleavage by
      the caspases present in the cytosolic extracts. Furthermore, liver PARP was not
      cleaved by recombinant human caspase-3. It is concluded that PARP proteolysis
      cannot be used as a marker for hepatocyte apoptosis.

PMID- 10079204
TI  - Structural features underlying the unusual mode of calmodulin phosphorylation by
      protein kinase CK2: A study with synthetic calmodulin fragments.
AB  - To shed light on the paradoxical behaviour of calmodulin, whose phosphorylation
      is inhibited by the regulatory beta-subunit of protein kinase CK2, a series of
      peptides encompassing the phosphoacceptor sites of calmodulin have been
      synthesized and assayed as substrates of CK2 alpha-subunit either alone or
      combined with the beta-subunit. The shortest peptide whose phosphorylation is
      reduced instead of being enhanced by the beta-subunit encompasses the sequence 68
      106, including the central helix and the Ca2+-binding loop-III. In contrast, the
      phosphorylation of a peptide encompassing loop II and the central helix (54-92)
      is stimulated, like that of several shorter peptides, by the beta-subunit. Our
      data localize to the C-terminal domain of calmodulin the structural elements that
      are responsible for inverted susceptibility to beta-subunit regulation.

PMID- 10079206
TI  - Physiologically based modeling of 1,2,4-trimethylbenzene inhalation
      toxicokinetics.
AB  - A physiologically based toxicokinetic model was developed for inhalation exposure
      of 1,2,4-trimethylbenzene (TMB) in man. The model consists of six compartments
      for TMB and one compartment for the metabolite 3,4-dimethylhippuric acid (DMHA).
      Based on previous experimental findings from human exposures to TMB, liver
      metabolism was divided in two pathways, one of the first order and one of the
      Michaelis-Menten type. Muscle tissue was split in two compartments to account for
      working and resting muscle tissues during bicycle exercise. The model was used to
      investigate how various factors influence potential biomarkers of exposure, i.e.,
      TMB in blood and exhaled air and DMHA in urine. Increasing the work load from
      rest to moderate exercise (100 W) more than doubled all biomarker levels end of
      shift. The effect on next morning levels was even more pronounced, illustrated by
      a fivefold increase in the DMHA excretion rate. Simulations of five daily 8-h
      exposures suggest that biomarker levels end of shift remain fairly constant
      whereas the levels prior to shift increase gradually during the week. This
      suggests that end of shift levels reflect the exposure of the same day whereas
      levels Friday morning reflect exposure during the entire working week.
      Simulations with randomly generated exposures show that the variability due to
      fluctuating exposure is lower next morning than end of shift. End of shift
      exhalation rate of TMB is more sensitive to fluctuation than TMB in venous blood
      and DMHA in urine. Biomarker levels for 25 ppm exposure at different sampling
      times are given.

PMID- 10079207
TI  - ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate
      transporter.
AB  - We have recently demonstrated mutually inhibitory ATP-dependent transport of
      dinitrophenyl-S-glutathione (DNP-SG) and doxorubicin by DNP-SG ATPase purified
      from human erythrocyte membranes (S. Awasthi et al., 1998a,b). Our previous
      studies indicate a broad substrate specificity for this transport mechanism,
      including some P-glycoprotein substrates. Present studies were carried out to
      determine whether colchicine (COL), a classical P-glycoprotein substrate, could
      be transported by purified human erythrocyte DNP-SG ATPase reconstituted in
      artificial liposomes. We also investigated whether leukotriene C4 (LTC4), an
      endogenous proinflammatory glutathione-conjugate derived from arachidonic acid,
      would inhibit colchicine transport. Uptake of COL was compared in proteoliposomes
      reconstituted with the purified DNP-SG ATPase as well as control liposomes in the
      presence or absence of ATP. Increased colchicine uptake was observed upon
      addition of ATP to proteoliposomes, but not control liposomes. Uptake was linear
      with respect to the amount of vesicle protein used. Sensitivity to osmolarity was
      consistent with intravesicular COL accumulation. The ATP-dependent colchicine
      uptake was sensitive to temperature in a manner consistent with a protein
      mediated transport process with activation energy of 7.3 kcal/mol. Time-dependent
      COL uptake by proteoliposomes in the presence of ATP was consistent with a single
      compartment model with an apparent rate constant of 0.21 +/- 0.02 min-1. Kinetic
      studies indicated a saturable behavior with respect to ATP (Km 2.3 +/- 0.7 mM)
      and colchicine (Km 4.3 +/- 0.2 microM). LTC4 was found to be a competitive
      inhibitor of COL transport (Kis 16.4 microM). Since DNP-SG ATPase is present in
      many tissues, it may play an important role in determining colchicine
      accumulation in cells. Increased LTC4 would tend to increase cellular COL
      accumulation.

PMID- 10079208
TI  - Atypical antipsychotic-induced neutropenia in dogs.
AB  - DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically
      related to clozapine, which exerts its desired pharmacologic effects through
      selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes.
      Clozapine therapy is clinically associated with severe granulocytopenia in a
      small subset of patients. In the course of a 3-month toxicity study in dogs,
      severe neutropenia, thrombocytopenia, marked myeloid and erythroid left-shifted
      bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs'
      tests, and hypergammaglobulinemia occurred in individual females dosed with 30
      mg/kg/day of DMP 406. Related but less severe changes were also observed in
      males. Sera or purified immunoglobulins from affected and control dogs were
      tested in methylcellulose-based, canine hematopoietic colony-forming unit (CFU)
      assays with or without DMP 406. Neither size nor number of erythroid or myeloid
      CFUs differed between cultures containing control or affected dog serum
      components. Sera from individual affected dogs but not controls resulted in
      moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow
      stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in
      a concentration-dependent reduction of erythroid and myeloid CFUs with an
      approximate IC50 of 3.0 microg/mL. Taken together, DMP 406-induced
      granulocytopenia and bone marrow dyscrasia appear likely to result from both
      immune-mediated and direct drug-induced myelotoxicity.

PMID- 10079209
TI  - Developmental vasculotoxicity associated with inhibition of semicarbazide
      sensitive amine oxidase.
AB  - The endogenous substrate(s) and physiological function(s) of semicarbazide
      sensitive amine oxidase (SSAO), a group of enzymes exhibiting highest activity in
      vascular smooth muscle cells of the mammalian aortic wall, remain undetermined.
      This study examines the pathophysiological effects in the thoracic aortic wall
      resulting from specific in vivo SSAO inhibition. Weanling Sprague-Dawley rats
      were treated acutely or chronically with either semicarbazide hydrochloride or
      the allylamine derivatives MDL-72274 or MDL-72145 (Marion Merrell Dow Research
      Institute, Cincinnati, OH). Treatment with these compounds produced acute (6 and
      24 h) and chronic (21 day) lowering of SSAO activity in aorta and lung with
      little effect on the activity of the vital matrix-forming enzyme, lysyl oxidase,
      in aortas of chronically treated animals. Chronic SSAO inhibition produced
      lesions consisting of striking disorganization of elastin architecture within the
      aortic media accompanied by degenerative medial changes and metaplastic changes
      in vascular smooth muscle cells. No significant difference in the total weight of
      dry, lipid-extracted aortic elastin and collagen components were observed between
      chronically SSAO inhibited and control animals. However, the amount of mature
      elastin was lowered and mature collagen was raised in the aortas of animals
      treated chronically with semicarbazide. Descending thoracic aortic rings isolated
      from chronically SSAO-inhibited animals had larger cross-sectional diameters
      (i.e., exhibited dilation) when compared to corresponding rings from control
      animals. This study demonstrates that developmental toxicity, characterized by
      striking vascular lesions and dilated thoracic aortas, can result from specific
      in vivo SSAO inhibition, suggesting a role for SSAO in connective tissue matrix
      development and maintenance, and specifically in the development of normal
      elastin.

PMID- 10079210
TI  - Cytotoxicity and induction of proinflammatory cytokines from human monocytes
      exposed to fine (PM2.5) and coarse particles (PM10-2.5) in outdoor and indoor
      air.
AB  - Increased incidence of mortality and morbidity due to cardiopulmonary
      complications has been found to associate with elevated levels of particulate air
      pollution (particulate matter with an aerodynamic diameter < 10 microm, PM10 and
      <2.5 microm, PM2. 5). Lung injury and an imbalance of inflammatory mediators are
      proposed causative mechanisms, while the toxic constituents may be acidity,
      transition metals, organic, and biogenic materials. To compare the ability of
      inhalable fine particles (PM2.5), and coarse particles (PM10-2.5) to cause cell
      injury and cytokine production in monocytes, dichotomous Andersen samplers were
      used to collect size-fractionated PM10 for in vitro testing of the particle
      extracts. Particles from both outdoor and indoor air were collected onto Teflon
      filters, on nine separate occasions. Each filter was water extracted and each
      extract assessed for ability to cause cell death, as well as interleukin (IL)-6
      and IL-8 production in human monocytes. Significant toxicity and cytokine
      production was induced by outdoor PM10-2.5, but not by outdoor PM2.5 or the
      particles collected indoors. Outdoor PM10-2.5 induced 20 times the amounts of IL
      6 and IL-8 than the fine particles. Cytotoxicity was inhibited by deferoxamine, a
      chelator of transition metals, while cytokine production was not. On the other
      hand, lipopolysaccharide binding protein (LBP) completely inhibited cytokine
      induction by PM10-2.5, suggesting that gram-negative bacteria and/or endotoxins
      are components of PM10-2.5. The effective proinflammatory effects of endotoxin on
      macrophages may upset lung homeostasis while metals-induced cytotoxicity/necrosis
      may set up inflammation independent of macrophage-derived cytokines.

PMID- 10079211
TI  - Perinatal exposure to aged and diluted sidestream cigarette smoke produces airway
      hyperresponsiveness in older rats.
AB  - Exposing rats to aged and diluted sidestream cigarette smoke (ADSS) throughout in
      utero and postnatal life results in airway hyperresponsiveness and an increase in
      pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) in 7- to
      10-week-old rats. Since human epidemiologic studies suggest that perinatal
      exposure to environmental tobacco smoke (ETS) may be detrimental to the lung
      function of older children, this study was designed to determine if perinatal
      exposure alone results in airway hyperresponsiveness and increased PNECs/NEBs
      later in life in rats. Pregnant Sprague-Dawley rats were exposed to filtered air
      (FA, n = 7) or ADSS (1 mg/m3 total suspended particulates, n = 7) for 4 to 6
      h/day starting on Day 3 of gestation. Their pups continued to receive the same
      exposure regimen postnatally until 21 days of age. Thereafter all pups were
      exposed to FA until about 8 weeks of age. The airway responsiveness of one female
      pup from each litter was then assessed using an isolated perfused lung system
      whereby increasing doses of methacholine (-9.25 to -7.50 log mol) were
      administered into the pulmonary artery and lung resistance (Rl), dynamic
      compliance (Cdyn), and pulmonary pressure (Ppa) were measured. The number of
      PNECs/NEBs and mast cells per millimeter basal lamina were determined using
      immunocytochemical and histological staining and morphometric analysis.
      Statistics were performed using an unpaired Student's t test and repeated
      measures analysis of variance. Perinatal ADSS exposure enhanced methacholine
      induced changes in Rl (p = 0.02), Cdyn (p = 0.004), and Ppa (p = 0.007). At the
      highest dose of methacholine, Rl in the ADSS-exposed lungs was threefold that in
      FA-exposed lungs. Although total PNEC number increased approximately twofold in
      the ADSS-exposed animals, this change was not found to be statistically
      significant. Mast cell number also was not different between groups. These data
      suggest that exposure to ADSS during the perinatal period followed by 5 weeks
      exposure to FA induces airway hyperresponsiveness in the absence of a significant
      change in PNECs, NEBs, or mast cells.

PMID- 10079212
TI  - Stimulation of oscillatory uterine contraction by the PCB mixture Aroclor 1242
      may involve increased [Ca2+]i through voltage-operated calcium channels.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants
      associated with spontaneous abortion and shortened gestation length in women and
      animals. In previous studies, we showed that PCB mixtures and noncoplanar ortho
      substituted PCB congeners increased contractions in pregnant rat uterus. In the
      present study, we hypothesized that the PCB mixture Aroclor 1242 (A1242)
      stimulates oscillatory uterine contraction in pregnant uterus by increasing
      intracellular calcium concentration ([Ca2+]i). Pretreatment of uterine strips
      with ryanodine or thapsigargin, to deplete specific intracellular calcium stores,
      did not prevent the increased frequency of oscillatory contraction due to 50
      microM A1242, whereas thapsigargin effectively blocked carbachol-induced
      stimulation of uterine contraction. However, 100 microM A1242 was unable to
      increase contraction in the absence of extracellular calcium or in the presence
      of the voltage-operated L-type calcium channel blocker nifedipine. A1242 (100
      microM) was observed to partially depolarize the cell membrane of myometrial
      cells from pregnant rats, as measured with a potential-sensitive carbocyanine
      dye. Changes of [Ca2+]i were monitored in single myometrial cells loaded with the
      fluorescent calcium-sensitive probe fura-2. Cells exposed to 100 microM A1242
      showed a delayed and sustained increase of [Ca2+]i, and this increase was
      completely blocked in the absence of extracellular calcium or the presence of
      nifedipine. Therefore, the data suggest that depolarization of the cell membrane
      by A1242 enabled myometrial cells to increase [Ca2+]i through activation of
      voltage-operated calcium channels, and the increased [Ca2+]i consequently
      stimulated contraction of uterine smooth muscle.

PMID- 10079213
TI  - Acetaminophen-induced proliferation of breast cancer cells involves estrogen
      receptors.
AB  - Previous studies have shown that acetaminophen, a common analgesic/antipyretic,
      induces proliferation of cultured breast cancer cells containing both estrogen
      and progesterone receptors (ER+/PR+). The main objective of this study was to
      evaluate the involvement of ERs in this effect. First, the effects of therapeutic
      acetaminophen concentrations were compared in breast cancer cells with high ERs
      and in T47Dco cells with lower ERs, to determine if acetaminophen-induced
      proliferation depends on ER levels. Second, the effects of two antiestrogens (ICI
      182,780 and 4'-hydroxytamoxifen) on acetaminophen-induced proliferation were
      determined in three human breast cancer cell lines: two ER+/PR+ (MCF7, T47D) and
      one ER-/PR- (MDA-MB-231). Third, ER binding assays were performed in MCF7 cells
      to determine if acetaminophen competed with estradiol for binding to ERs.
      Proliferation endpoints monitored included percent cells in the DNA synthesis
      phase of the cell cycle, 3H-thymidine incorporation into DNA, and cell number.
      Acetaminophen did not induce DNA synthesis in T47Dco cells, but did in cells with
      higher ER levels, suggesting high ER levels are necessary for acetaminophen to
      induce proliferation. Antiestrogens inhibited acetaminophen-induced proliferation
      in ER+/PR+ cells while no effects were observed in ER-/PR- cells, further
      supporting ER involvement. However, acetaminophen did not compete with estradiol
      for binding to ERs in ER+/PR+ cells. Collectively, these data suggest that
      acetaminophen induces breast cancer cell proliferation via ERs without binding to
      ERs like estradiol. The second purpose of this study was to determine if
      acetaminophen is estrogenic/antiestrogenic in vivo (uterotrophic assays).
      Acetaminophen has no antiestrogenic/estrogenic activity in mice or rats uteri.

PMID- 10079214
TI  - Lead activates nuclear transcription factor-kappaB, activator protein-1, and
      amino-terminal c-Jun kinase in pheochromocytoma cells.
AB  - Lead (Pb) is a ubiquitous environmental contaminant that produces variety of
      effects on the central and peripheral nervous system, induces inflammatory
      response, and modulates immune functions. Though increase in lipid peroxidation
      and reactive oxygen intermediates (ROI) have been observed in Pb-induced
      toxicity, the molecular mechanism underlying these effects is largely unknown.
      Since nuclear factor kappa B (NF-kappaB) and activator protein (AP-1) are known
      to be activated by oxidative stress, we hypothesized that Pb-induced effects may
      be modulated via these transcription factors. The effects of Pb on NF-kappaB, AP
      1, and related kinases were studied in pheochromocytoma cells (PC-12). Our
      results showed that treatment of murine PC-12 cells with Pb resulted in
      activation of NF-kappaB and degradation of IkappaBalpha (the inhibitory subunit
      of NF-kappaB). Pb-induced NF-kappaB dependent gene expression was also enhanced.
      The binding of Pb-induced NF-kappaB to DNA was blocked by antibodies for p65 and
      p50 but not by c-Rel or nonspecific antibodies such as cyclin D-1 and preimmune
      serum, suggesting that NF-kappaB consisted of p65 and p50 subunits. Similar to
      its effects on NF-kappaB, Pb also activated AP-1 in a time- and dose-dependent
      manner. Besides activating these transcription factors, Pb was also found to
      upregulate the related kinases such as mitogen activated protein kinase kinase
      (MEK) and c-Jun N-terminal kinase (JNK) (also known as stress-activated protein
      kinase) in a dose- and time-dependent manner. Thus, these results suggest that NF
      kappaB, AP-1, MEK, and JNK may be important mediators of Pb-induced signaling in
      gene expression mediating inflammatory response and immunomodulation.

PMID- 10079215
TI  - The nature of halogen substitution determines the mode of cytotoxicity of
      halopropanols.
AB  - The cytochrome P450-dependent generation of reactive metabolites from 1,3
      dichloropropanol and 1,3-dibromopropanol was assessed in a microsomal thiol
      depletion assay, while the toxicity of these compounds was assessed in rat
      hepatocyte cultures and in the 3T3 cell line. Thiol-depleting metabolites of both
      compounds were generated in the microsomal assay; however, only dibromopropanol
      extensively depleted glutathione when glutathione S-transferase was used as the
      enzyme source. The cytotoxicity of dichloropropanol was both cytochrome P450- and
      glutathione-dependent, whereas that of dibromopropanol was glutathione-dependent
      but largely independent of cytochrome P450. These results indicate that the
      mechanisms underlying the cytotoxicity of halopropanols are dependent on the
      nature of the halogen substitution and that microsomal and cellular assays for
      reactive metabolite generation may yield conflicting results.

PMID- 10079216
TI  - Volume 151, number 2 (1998), in article no. TO988472, "Biopersistence of
      synthetic vitreous fibers and amosite asbestos in the rat lung following
      Inhalation," by T. W. Hesterberg, G. Chase, C. Axten, W. C. Miller, R. P.
      Musselman, O. Kamstrup, J. Hadley, C. Morscheidt, D. M. Bernstein, and P.
      Thevenaz, pages 262-275 

PMID- 10079218
TI  - Chemical index for volume 155 

PMID- 10079219
TI  - Shoot apical meristem and cotyledon formation during Arabidopsis embryogenesis:
      interaction among the CUP-SHAPED COTYLEDON and SHOOT MERISTEMLESS genes.
AB  - The shoot apical meristem and cotyledons of higher plants are established during
      embryogenesis in the apex. Redundant CUP-SHAPED COTYLEDON 1 (CUC1) and CUC2 as
      well as SHOOT MERISTEMLESS (STM) of Arabidopsis are required for shoot apical
      meristem formation and cotyledon separation. To elucidate how the apical region
      of the embryo is established, we investigated genetic interactions among CUC1,
      CUC2 and STM, as well as the expression patterns of CUC2 and STM mRNA. Expression
      of these genes marked the incipient shoot apical meristem as well as the
      boundaries of cotyledon primordia, consistent with their roles for shoot apical
      meristem formation and cotyledon separation. Genetic and expression analyses
      indicate that CUC1 and CUC2 are redundantly required for expression of STM to
      form the shoot apical meristem, and that STM is required for proper spatial
      expression of CUC2 to separate cotyledons. A model for pattern formation in the
      apical region of the Arabidopsis embryo is presented.

PMID- 10079220
TI  - Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5.
AB  - The transforming growth factor-beta (TGF-beta) signals are mediated by a family
      of at least nine SMAD proteins, of which SMAD5 is thought to relay signals of the
      bone morphogenetic protein (BMP) pathway. To investigate the role of SMAD5 during
      vertebrate development and tumorigenesis, we disrupted the Smad5 gene by
      homologous recombination. We showed that Smad5 was expressed predominantly in
      mesenchyme and somites during embryogenesis, and in many tissues of the adult.
      Mice homozygous for the mutation died between days 10.5 and 11.5 of gestation due
      to defects in angiogenesis. The mutant yolk sacs lacked normal vasculature and
      had irregularly distributed blood cells, although they contained hematopoietic
      precursors capable of erythroid differentiation. Smad5 mutant embryos had
      enlarged blood vessels surrounded by decreased numbers of vascular smooth muscle
      cells, suffered massive apoptosis of mesenchymal cells, and were unable to direct
      angiogenesis in vitro. These data suggest that SMAD5 may regulate endothelium
      mesenchyme interactions during angiogenesis and that it is essential for
      mesenchymal survival.

PMID- 10079221
TI  - p27(Kip1) links cell proliferation to morphogenesis in the developing organ of
      Corti.
AB  - Strict control of cellular proliferation is required to shape the complex
      structures of the developing embryo. The organ of Corti, the auditory
      neuroepithelium of the inner ear in mammals, consists of two types of terminally
      differentiated mechanosensory hair cells and at least four types of supporting
      cells arrayed precisely along the length of the spiral cochlea. In mice, the
      progenitors of greater than 80% of both hair cells and supporting cells undergo
      their terminal division between embryonic day 13 (E13) and E14. As in humans,
      these cells persist in a non-proliferative state throughout the adult life of the
      animal. Here we report that the correct timing of cell cycle withdrawal in the
      developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor
      that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is
      induced in the primordial organ of Corti between E12 and E14, correlating with
      the cessation of cell division of the progenitors of the hair cells and
      supporting cells. In wild-type animals, p27(Kip1) expression is downregulated
      during subsequent hair cell differentiation, but it persists at high levels in
      differentiated supporting cells of the mature organ of Corti. In mice with a
      targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell
      progenitors continues after E14, leading to the appearance of supernumerary hair
      cells and supporting cells. In the absence of p27(Kip1), mitotically active cells
      are still observed in the organ of Corti of postnatal day 6 animals, suggesting
      that the persistence of p27(Kip1) expression in mature supporting cells may
      contribute to the maintenance of quiescence in this tissue and, possibly, to its
      inability to regenerate. Homozygous mutant mice are severely hearing impaired.
      Thus, p27(Kip1) provides a link between developmental control of cell
      proliferation and the morphological development of the inner ear.

PMID- 10079222
TI  - Hedgehog is required for activation of engrailed during regeneration of
      fragmented Drosophila imaginal discs.
AB  - Surgically fragmented Drosophila appendage primordia (imaginal discs) engage in
      wound healing and pattern regulation during short periods of in vivo culture.
      Prothoracic leg disc fragments possess exceptional regulative capacity,
      highlighted by the ability of anterior cells to convert to posterior identity and
      establish a novel posterior compartment. This anterior/posterior conversion
      violates developmental lineage restrictions essential for normal growth and
      patterning of the disc, and thus provides an ideal model for understanding how
      cells change fate during epimorphic pattern regulation. Here we present evidence
      that the secreted signal encoded by hedgehog directs anterior/posterior
      conversion by activating the posterior-specific transcription factor engrailed in
      regulating anterior cells. In the absence of hedgehog activity, prothoracic leg
      disc fragments fail to undergo anterior/posterior conversion, but can still
      regenerate missing anterior pattern elements. We suggest that hedgehog
      independent regeneration within the anterior compartment (termed integration) is
      mediated by the positional cues encoded by wingless and decapentaplegic. Taken
      together, our results provide a novel mechanistic interpretation of imaginal disc
      pattern regulation and permit speculation that similar mechanisms could govern
      appendage regeneration in other organisms.

PMID- 10079223
TI  - The flat-top gene is required for the expansion and regionalization of the
      telencephalic primordium.
AB  - The telencephalic vesicles form in the mouse embryo by the expansion of precursor
      regions in the anterior neural tube. Once the vesicles have formed, discrete
      dorsal and ventral territories can be recognized that later give rise to cortical
      and subcortical structures, respectively. To investigate the mechanisms that
      regulate the expansion and regionalization of the telencephalon, we have carried
      out a screen to identify recessive mutations that disrupt these events. We
      isolated a mouse mutant in which an early and critical step in development of the
      telencephalic vesicles is disrupted. Telencephalic primordia are present in flat
      top embryos but they fail to progress to form the telencephalic vesicles. An
      increased rate of proliferation in the forebrain neurectoderm that accompanies
      telencephalic expansion in wild-type embryos fails to occur in flat-top embryos.
      Regionalization events that would normally take place during expansion of the
      primordia also fail to occur. Thus the phenotype of the flat-top mouse reveals
      that outgrowth of the telencephalic vesicles and their regionalization are
      coupled processes.

PMID- 10079224
TI  - A developmental pathway controlling outgrowth of the Xenopus tail bud.
AB  - We have developed a new assay to identify factors promoting formation and
      outgrowth of the tail bud. A piece of animal cap filled with the test mRNAs is
      grafted into the posterior region of the neural plate of a host embryo. With this
      assay we show that expression of a constitutively active Notch (Notch ICD) in the
      posterior neural plate is sufficient to produce an ectopic tail consisting of
      neural tube and fin. The ectopic tails express the evenskipped homologue Xhox3, a
      marker for the distal tail tip. Xhox3 will also induce formation of an ectopic
      tail in our assay. We show that an antimorphic version of Xhox3, Xhox3VP16, will
      prevent tail formation by Notch ICD, showing that Xhox3 is downstream of Notch
      signalling. An inducible version of this reagent, Xhox3VP16GR, specifically
      blocks tail formation when induced in tailbud stage embryos, comfirming the
      importance of Xhox3 for tail bud outgrowth in normal development. Grafts
      containing Notch ICD will only form tails if placed in the posterior part of the
      neural plate. However, if Xwnt3a is also present in the grafts they can form
      tails at any anteroposterior level. Since Xwnt3a expression is localised
      appropriately in the posterior at the time of tail bud formation it is likely to
      be responsible for restricting tail forming competence to the posterior neural
      plate in our assay. Combined expression of Xwnt3a and active Notch in animal cap
      explants is sufficient to induce Xhox3, provoke elongation and form neural tubes.
      Conservation of gene expression in the tail bud of other vertebrates suggests
      that this pathway may describe a general mechanism controlling tail outgrowth and
      secondary neurulation.

PMID- 10079225
TI  - The role of SF/HGF and c-Met in the development of skeletal muscle.
AB  - Hypaxial skeletal muscles develop from migratory and non-migratory precursor
      cells that are generated by the lateral lip of the dermomyotome. Previous work
      shows that the formation of migratory precursors requires the c-Met and SF/HGF
      genes. We show here that in mice lacking c-Met or SF/HGF, the initial development
      of the dermomyotome proceeds appropriately and growth and survival of cells in
      the dermomyotome are not affected. Migratory precursors are also correctly
      specified, as monitored by the expression of Lbx1. However, these cells remain
      aggregated and fail to take up long range migration. We conclude that parallel
      but independent cues converge on the migratory hypaxial precursors in the
      dermomyotomal lip after they are laid down: a signal given by SF/HGF that
      controls the emigration of the precursors, and an as yet unidentified signal that
      controls Lbx1. SF/HGF and c-Met act in a paracrine manner to control emigration,
      and migratory cells only dissociate from somites located close to SF/HGF
      expressing cells. During long range migration, prolonged receptor-ligand
      interaction appears to be required, as SF/HGF is expressed both along the routes
      and at the target sites of migratory myogenic progenitors. Mice that lack c-Met
      die during the second part of gestation due to a placental defect. Rescue of the
      placental defect by aggregation of tetraploid (wild type) and diploid (c-Met-/-)
      morulae allows development of c-Met mutant animals to term. They lack muscle
      groups that derive from migratory precursor cells, but display otherwise normal
      skeletal musculature.

PMID- 10079226
TI  - Smad5 knockout mice die at mid-gestation due to multiple embryonic and
      extraembryonic defects.
AB  - Smad5 has been implicated as a downstream signal mediator for several bone
      morphogenetic proteins (BMPs). To understand the in vivo function of Smad5, we
      generated mice deficient in Smad5 using embryonic stem (ES) cell technology.
      Homozygous mutant embryos die between E9.5 and E11.5, and display variable
      phenotypes. Morphological defects are first detected at E8.0 in the developing
      amnion, gut and heart (the latter defect being similar to BMP-2 knockout mice).
      At later stages, mutant embryos fail to undergo proper turning, have craniofacial
      and neural tube abnormalities, and are edematous. In addition, several
      extraembryonic lesions are observed. After E9.0, the yolk sacs of the mutants
      contain red blood cells but lack a well-organized vasculature, which is
      reminiscent of BMP-4, TGF-beta1 and TGF-beta type II receptor knockout mice. In
      addition, the allantois of many Smad5 mutants is fused to the chorion, but is not
      well-elongated. A unique feature of the Smad5 mutant embryos is that ectopic
      vasculogenesis and hematopoiesis is observed in the amnion, likely due to
      mislocation of allantois tissue. Despite the expression of Smad5 from
      gastrulation onwards, and in contrast to knockouts of Smad2 and Smad4, Smad5 only
      becomes essential later in extraembryonic and embryonic development.

PMID- 10079227
TI  - A multigene locus containing the Manx and bobcat genes is required for
      development of chordate features in the ascidian tadpole larva.
AB  - The Manx gene is required for the development of the tail and other chordate
      features in the ascidian tadpole larva. To determine the structure of the Manx
      gene, we isolated and sequenced genomic clones from the tailed ascidian Molgula
      oculata. The Manx gene contains 9 exons and encodes both major and minor Manx
      mRNAs, which differ in the length of their 5' untranslated regions. The coding
      region of the single-copy bobcat gene, which encodes a DEAD-box RNA helicase, is
      embedded within the first Manx intron. The organization of the bobcat and Manx
      transcription units was determined by comparing genomic and cDNA clones. The Manx
      bobcat gene locus has an unusual organization in which a non-coding first exon is
      alternatively spliced at the 5' end of two different mRNAs. The bobcat and Manx
      genes are expressed coordinately during oogenesis and embryogenesis, but not
      during spermatogenesis, in which bobcat mRNA accumulates independently of Manx
      mRNA. Similar to Manx, zygotic bobcat transcripts accumulate in the embryonic
      primordia responsible for generating chordate features, including the dorsal
      neural tube and notochord, are downregulated during embryogenesis in the tailless
      species Molgula occulta and are upregulated in M. occulta X M. oculata hybrids,
      which restore these chordate features. Antisense experiments indicate that
      zygotic bobcat expression is required for development of the same suite of
      chordate features as Manx. The results show that the Manx-bobcat gene complex has
      a role in the development of chordate features in ascidian tadpole larvae.

PMID- 10079228
TI  - Mouse primordial germ cells lacking beta1 integrins enter the germline but fail
      to migrate normally to the gonads.
AB  - Primordial germ cells are the founder cells of the gametes. They are set aside at
      the initial stages of gastrulation in mammals, become embedded in the hind-gut
      endoderm, then actively migrate to the sites of gonad formation. The molecular
      basis of this migration is poorly understood. Here we sought to determine if
      members of the integrin family of cell surface receptors are required for
      primordial germ cell migration, as integrins have been implicated in the
      migration of several other motile cell types. We have established a line of mice
      which express green fluorescent protein in germline cells that has enabled us to
      efficiently purify primordial germ cells at different stages by flow cytometry.
      We have catalogued the spectrum of integrin subunit expression by primordial germ
      cells during and after migration, using flow cytometry, immunocytochemistry and
      RT-PCR. Through analysis of integrin beta1(-/-)-->wild-type chimeras, we show
      that embryonic cells lacking beta1 integrins can enter the germline. However,
      integrin beta1(-/-) primordial germ cells do not colonize the gonad efficiently.
      Embryos with targeted deletion of integrin subunit alpha3, alpha6, or alphaV show
      no major defects in primordial germ cell migration. These results demonstrate a
      role for beta1-containing integrins in the development of the germline, although
      an equivalent role for * integrin subunit(s) has yet to be established.

PMID- 10079229
TI  - Pax3 functions in cell survival and in pax7 regulation.
AB  - In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the
      paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop
      muscular and neural tube defects; furthermore, Pax3 is essential for the proper
      activation of the myogenic determination factor gene, MyoD, during early muscle
      development and PAX3 chromosomal translocations result in muscle tumors,
      providing evidence that Pax3 has diverse functions in myogenesis. To investigate
      the specific functions of Pax3 in development, we have examined cell survival and
      gene expression in presomitic mesoderm, somites and neural tube of developing
      wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression
      by antisense oligonucleotides significantly impairs MyoD activation by signals
      from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm
      (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3
      mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but
      MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed
      somites, but not in the neural tube or mature somites. In neural tube and somite
      regions where cell survival is maintained, the closely related Pax7 gene is
      upregulated, and its expression becomes expanded into the dorsal neural tube and
      somites, where Pax3 would normally be expressed. These results establish that
      Pax3 has complementary functions in MyoD activation and inhibition of apoptosis
      in the somitic mesoderm and in repression of Pax7 during neural tube and somite
      development.

PMID- 10079230
TI  - Induction of alveolar type II cell differentiation in embryonic tracheal
      epithelium in mesenchyme-free culture.
AB  - We have previously shown that fetal lung mesenchyme can reprogram embryonic rat
      tracheal epithelium to express a distal lung phenotype. We have also demonstrated
      that embryonic rat lung epithelium can be induced to proliferate and
      differentiate in the absence of lung mesenchyme. In the present study we used a
      complex growth medium to induce proliferation and distal lung epithelial
      differentiation in embryonic tracheal epithelium. Day-13 embryonic rat tracheal
      epithelium was separated from its mesenchyme, enrobed in growth factor-reduced
      Matrigel, and cultured for up to 7 days in medium containing charcoal-stripped
      serum, insulin, epidermal growth factor, hepatocyte growth factor, cholera toxin,
      fibroblast growth factor 1 (FGF1), and keratinocyte growth factor (FGF7). The
      tracheal epithelial cells proliferated extensively in this medium, forming
      lobulated structures within the extracellular matrix. Many of the cells
      differentiated to express a type II epithelial cell phenotype, as evidenced by
      expression of SP-C and osmiophilic lamellar bodies. Deletion studies showed that
      serum, insulin, cholera toxin, and FGF7 were necessary for maximum growth. While
      no single deletion abrogated expression of SP-C, deleting both FGF7 and FGF1
      inhibited growth and prevented SP-C expression. FGF7 or FGF1 as single additions
      to the medium, however, were unable to induce SP-C expression, which required the
      additional presence of serum or cholera toxin. FGF10, which binds the same
      receptor as FGF7, did not support transdifferentiation when used in place of
      FGF7. These data indicate that FGF7 is necessary, but not sufficient by itself,
      to induce the distal rat lung epithelial phenotype, and that FGF7 and FGF10 play
      distinct roles in lung development.

PMID- 10079231
TI  - Notch signaling imposes two distinct blocks in the differentiation of C2C12
      myoblasts.
AB  - Notch signal transduction regulates expression of downstream genes through the
      activation of the DNA-binding protein Su(H)/CBF1. In Drosophila most of Notch
      signaling requires Su(H); however, some Notch-dependent processes occur in the
      absence of Su(H) suggesting that Notch signaling does not always involve
      activation of this factor. Using constitutively active forms of Notch lacking
      CBF1-interacting sequences we identified a Notch signaling pathway that inhibits
      myogenic differentiation of C2C12 myoblasts in the absence of CBF1 activation.
      Here we show that ligand-induced Notch signaling suppresses myogenesis in C2C12
      myoblasts that express a dominant negative form of CBF1, providing additional
      evidence for CBF1-independent Notch signal transduction. Surprisingly mutant
      forms of Notch deficient in CBF1 activation are unable to antagonize MyoD
      activity, despite the fact that they inhibit myogenesis. Moreover, Notch-induced
      antagonism of MyoD requires CBF1 suggesting that the CBF1-dependent pathway
      mediates a cell-type-specific block in the myogenic program. However, Notch
      signaling in the absence of CBF1 activation blocks both myogenesis and
      osteogenesis, indicative of a general block in cellular differentiation. Taken
      together our data provide evidence for two distinct Notch signaling pathways that
      function to block differentiation at separate steps during the process of
      myogenesis in C2C12 myoblasts.

PMID- 10079232
TI  - LvNotch signaling mediates secondary mesenchyme specification in the sea urchin
      embryo.
AB  - Cell-cell interactions are thought to regulate the differential specification of
      secondary mesenchyme cells (SMCs) and endoderm in the sea urchin embryo. The
      molecular bases of these interactions, however, are unknown. We have previously
      shown that the sea urchin homologue of the LIN-12/Notch receptor, LvNotch,
      displays dynamic patterns of expression within both the presumptive SMCs and
      endoderm during the blastula stage, the time at which these two cell types are
      thought to be differentially specified (Sherwood, D. R. and McClay, D. R. (1997)
      Development 124, 3363-3374). The LIN-12/Notch signaling pathway has been shown to
      mediate the segregation of numerous cell types in both invertebrate and
      vertebrate embryos. To directly examine whether LvNotch signaling has a role in
      the differential specification of SMCs and endoderm, we have overexpressed
      activated and dominant negative forms of LvNotch during early sea urchin
      development. We show that activation of LvNotch signaling increases SMC
      specification, while loss or reduction of LvNotch signaling eliminates or
      significantly decreases SMC specification. Furthermore, results from a mosaic
      analysis of LvNotch function as well as endogenous LvNotch expression strongly
      suggest that LvNotch signaling acts autonomously within the presumptive SMCs to
      mediate SMC specification. Finally, we demonstrate that the expansion of SMCs
      seen with activation of LvNotch signaling comes at the expense of presumptive
      endoderm cells, while loss of SMC specification results in the endoderm expanding
      into territory where SMCs usually arise. Taken together, these results offer
      compelling evidence that LvNotch signaling directly specifies the SMC fate, and
      that this signaling is critical for the differential specification of SMCs and
      endoderm in the sea urchin embryo.

PMID- 10079233
TI  - Early specification of sensory neuron fate revealed by expression and function of
      neurogenins in the chick embryo.
AB  - The generation of sensory and autonomic neurons from the neural crest requires
      the functions of two classes of basic helix-loop-helix (bHLH) transcription
      factors, the Neurogenins (NGNs) and MASH-1, respectively (Fode, C., Gradwohl, G.,
      Morin, X., Dierich, A., LeMeur, M., Goridis, C. and Guillemot, F. (1998) Neuron
      20, 483-494; Guillemot, F., Lo, L.-C., Johnson, J. E., Auerbach, A., Anderson, D.
      J. and Joyner, A. L. (1993) Cell 75, 463-476; Ma, Q., Chen, Z. F., Barrantes, I.
      B., de la Pompa, J. L. and Anderson, D. J. (1998 Neuron 20, 469-482). We have
      cloned two chick NGNs and found that they are expressed in a subset of neural
      crest cells early in their migration. Ectopic expression of the NGNs in vivo
      biases migrating neural crest cells to localize in the sensory ganglia, and
      induces the expression of sensory neuron-appropriate markers in non-sensory crest
      derivatives. Surprisingly, the NGNs can also induce the expression of multiple
      pan-neuronal and sensory-specific markers in the dermomyotome, a mesodermal
      derivative. Taken together, these data suggest that a subset of neural crest
      cells may already be specified for a sensory neuron fate early in migration, as a
      consequence of NGN expression.

PMID- 10079234
TI  - Spatially regulated SpEts4 transcription factor activity along the sea urchin
      embryo animal-vegetal axis.
AB  - Because the transcription of the SpHE gene is regulated cell-autonomously and
      asymmetrically along the maternally determined animal-vegetal axis of the very
      early sea urchin embryo, its regulators provide an excellent entry point for
      investigating the mechanism(s) that establishes this initial polarity. Previous
      studies support a model in which spatial regulation of SpHE transcription relies
      on multiple nonvegetal positive transcription factor activities (Wei, Z.,
      Angerer, L. M. and Angerer, R. C. (1997) Dev. Biol. 187, 71-78) and a yeast one
      hybrid screen has identified one, SpEts4, which binds with high specificity to a
      cis element in the SpHE regulatory region and confers positive activation of SpHE
      promoter transgenes (Wei, Z., Angerer, R. C. and Angerer, L. M. (1999) Mol. Cell.
      Biol. 19, 1271-1278). Here we demonstrate that SpEts4 can bind to the regulatory
      region of the endogenous SpHE gene because a dominant repressor, created by
      fusing SpEts4 DNA binding and Drosophila engrailed repression domains, suppresses
      its transcription. The pattern of expression of the SpEts4 gene is consistent
      with a role in regulating SpHE transcription in the nonvegetal region of the
      embryo during late cleavage/early blastula stages. Although maternal transcripts
      are uniformly distributed in the egg and early cleaving embryo, they rapidly turn
      over and are replaced by zygotic transcripts that accumulate in a pattern
      congruent with SpHE transcription. In addition, in vivo functional tests show
      that the SpEts4 cis element confers nonvegetal transcription of a beta
      galactosidase reporter gene containing the SpHE basal promoter, and provide
      strong evidence that the activity of this transcription factor is an integral
      component of the nonvegetal transcriptional regulatory apparatus, which is
      proximal to, or part of, the mechanism that establishes the animal-vegetal axis
      of the sea urchin embryo.

PMID- 10079235
TI  - Tbx5 is essential for heart development.
AB  - Mutations in the Tbx5 transcription factor cause heart septal defects found in
      human Holt-Oram Syndrome. The complete extent to which Tbx5 functions in heart
      development, however, has not been established. Here we show that, in Xenopus
      embryos, Tbx5 is expressed in the early heart field, posterior to the cardiac
      homeobox transcription factor, Nkx2.5. During morphogenesis, Tbx5 is expressed
      throughout the heart tube except the anterior portion, the bulbus cordis. When
      Tbx5 activity is antagonized with a hormone-inducible, dominant negative version
      of the protein, the heart fails to develop. These results suggest that, in
      addition to its function in heart septation, Tbx5 has a more global role in
      cardiac specification and heart development in vertebrate embryos.

PMID- 10079236
TI  - Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional
      redundancy within the 60A subgroup.
AB  - Members of the BMP family of signaling molecules display a high conservation of
      structure and function, and multiple BMPs are often coexpressed in a variety of
      tissues during development. Moreover, distinct BMP ligands are capable of
      activating common pathways. Here we describe the coexpression of two members of
      the 60A subfamily of BMPs, Bmp5 and Bmp7, at a number of different sites in the
      embryo from gastrulation onwards. Previous studies demonstrate that loss of
      either Bmp5 or Bmp7 has negligible effects on development, suggesting these
      molecules functionally compensate for each other at early stages of embryonic
      development. Here we show this is indeed the case. Thus we find that Bmp5;Bmp7
      double mutants die at 10.5 dpc and display striking defects primarily affecting
      the tissues where these factors are coexpressed. The present analysis also
      uncovers novel roles for BMP signaling during the development of the allantois,
      heart, branchial arches, somites and forebrain. Bmp5 and Bmp7 do not appear to be
      involved in establishing pattern in these tissues, but are instead necessary for
      the proliferation and maintenance of specific cell populations. These findings
      are discussed with respect to potential mechanisms underlying cooperative
      signaling by multiple members of the TGF-beta superfamily.

PMID- 10079237
TI  - Goosecoid and mix.1 repress Brachyury expression and are required for head
      formation in Xenopus.
AB  - The Xenopus homologue of Brachyury, Xbra, is expressed in the presumptive
      mesoderm of the early gastrula. Induction of Xbra in animal pole tissue by
      activin occurs only in a narrow window of activin concentrations; if the level of
      inducer is too high, or too low, the gene is not expressed. Previously, we have
      suggested that the suppression of Xbra by high concentrations of activin is due
      to the action of genes such as goosecoid and Mix.1. Here, we examine the roles
      played by goosecoid and Mix.1 during normal development, first in the control of
      Xbra expression and then in the formation of the mesendoderm. Consistent with the
      model outlined above, inhibition of the function of either gene product leads to
      transient ectopic expression of Xbra. Such embryos later develop dorsoanterior
      defects and, in the case of interference with Mix.1, additional defects in heart
      and gut formation. Goosecoid, a transcriptional repressor, appears to act
      directly on transcription of Xbra. In contrast, Mix.1, which functions as a
      transcriptional activator, may act on Xbra indirectly, in part through activation
      of goosecoid.

PMID- 10079239
TI  - Launching the journal of molecular diagnostics 

PMID- 10079238
TI  - loco encodes an RGS protein required for Drosophila glial differentiation.
AB  - In Drosophila, glial cell development depends on the gene glial cells missing
      (gcm). gcm activates the expression of other transcription factors such as
      pointed and repo, which control subsequent glial differentiation. In order to
      better understand glial cell differentiation, we have screened for genes whose
      expression in glial cells depends on the activity of pointed. Using an enhancer
      trap approach, we have identified loco as such a gene. loco is expressed in most
      lateral CNS glial cells throughout development. Embryos lacking loco function
      have an normal overall morphology, but fail to hatch. Ultrastructural analysis of
      homozygous mutant loco embryos reveals a severe glial cell differentiation
      defect. Mutant glial cells fail to properly ensheath longitudinal axon tracts and
      do not form the normal glial-glial cell contacts, resulting in a disruption of
      the blood-brain barrier. Hypomorphic loco alleles were isolated following an EMS
      mutagenesis. Rare escapers eclose which show impaired locomotor capabilities.
      loco encodes the first two known Drosophila members of the family of Regulators
      of G-protein signalling (RGS) proteins, known to interact with the alpha subunits
      of G-proteins. loco specifically interacts with the Drosophila alphai-subunit.
      Strikingly, the interaction is not confined to the RGS domain. This interaction
      and the coexpression of LOCO and Galphai suggests a function of G-protein
      signalling for glial cell development.

PMID- 10079241
TI  - Rous-Whipple Award Lecture. Chemical features of peptide selection by the class
      II histocompatibility molecules.

PMID- 10079240
TI  - Genomic imprinting: implications for human disease.
AB  - Genomic imprinting refers to an epigenetic marking of genes that results in
      monoallelic expression. This parent-of-origin dependent phenomenon is a notable
      exception to the laws of Mendelian genetics. Imprinted genes are intricately
      involved in fetal and behavioral development. Consequently, abnormal expression
      of these genes results in numerous human genetic disorders including
      carcinogenesis. This paper reviews genomic imprinting and its role in human
      disease. Additional information about imprinted genes can be found on the Genomic
      Imprinting Website at http://www.geneimprint.com.

PMID- 10079243
TI  - Pathways of Egr-1-mediated gene transcription in vascular biology.

PMID- 10079244
TI  - Ectopic calcification: gathering hard facts about soft tissue mineralization.

PMID- 10079245
TI  - LKB1 somatic mutations in sporadic tumors.
AB  - Germline mutations of LKB1/Peutz-Jeghers syndrome gene predispose carriers to
      hamartomatous polyposis of the gastrointestinal tract as well as to cancer of
      different organ systems. Although Peutz-Jeghers syndrome patients frequently
      present with neoplasms of the colon, stomach, small intestine, pancreas, breast,
      ovaries, and cervix, somatic mutations appear to be rare in the sporadic tumor
      types thus far studied (colorectal, gastric, testicular, and breast cancers). To
      evaluate whether somatic mutations of LKB1 contribute to the tumorigenesis of yet
      unstudied tumor types, we screened 14 cell lines and 129 tumor specimens from
      different cancers for a genetic defect in LKB1. Six melanoma and eight myeloma
      cell lines were scrutinized for LKB1 somatic mutations by genomic sequencing. No
      changes were found in the coding LKB1 sequence and exon/intron boundaries. Next,
      we analyzed 12 pancreatic, 8 gastric, 12 ovarian granulosa cell, 26 cervical, 28
      lung, 24 soft tissue, and 19 renal tumors by single-strand conformational
      polymorphism analysis. Three changes in LKB1 coding nucleotide sequence were
      identified. One base pair deletion at A957 and G958 substitution by T occurred in
      a cervical adenocarcinoma sample, resulting in a frameshift and premature stop
      codon at position 335. Substitution of A581 by T occurred in a lung
      adenocarcinoma sample, resulting in the change of aspartic acid at position 194
      to valine. A loss of another allele was detected in this sample. One silent
      change, C1257T, was found in a pancreatic carcinoma sample. The changes were not
      present in the matched normal tissue DNA samples. Our results suggest that
      mutational inactivation of LKB1 is a rare event in most sporadic tumor types.

PMID- 10079246
TI  - Pancreatic expression of keratinocyte growth factor leads to differentiation of
      islet hepatocytes and proliferation of duct cells.
AB  - Keratinocyte growth factor, (KGF), a member of the fibroblast growth factor (FGF)
      family, is involved in wound healing. It also promotes the differentiation of
      many epithelial tissues and proliferation of epithelial cells as well as
      pancreatic duct cells. Additionally, many members of the highly homologous FGF
      family (including KGF), influence both growth and cellular morphology in the
      developing embryo. We have previously observed elevated levels of KGF in our
      interferon-gamma transgenic mouse model of pancreatic regeneration. To understand
      the role of KGF in pancreatic differentiation, we generated insulin promoter
      regulated KGF transgenic mice. Remarkably, we have found that ectopic KGF
      expression resulted in the emergence of hepatocytes within the islets of
      Langerhans in the pancreas. Additionally, significant intra-islet duct cell
      proliferation in the pancreata of transgenic KGF mice was observed. The
      unexpected appearance of hepatocytes and proliferation of intra-islet duct cells
      in the pancreata of these mice evidently stemmed directly from local exposure to
      KGF.

PMID- 10079247
TI  - Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of
      hepatocyte destruction to facilitate local tumor invasion.
AB  - This study demonstrates a novel role for the Fas pathway in the promotion of
      local tumor growth by inducing apoptotic cell death in normal hepatocytes at the
      tumor margin in colorectal hepatic metastases. Our results show that >85% of
      lymphocytes infiltrating colorectal liver cancer express high levels of Fas
      ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we
      showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression
      was restricted to tumor cells and infiltrating lymphocytes at the tumor margin.
      Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor
      margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro,
      primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas
      antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0%
      in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and
      human metastatic colon cancer cells cells are able to induce Fas-mediated
      apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced
      apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P =
      0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P =
      0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with
      control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P =
      0.004) in the presence of anti-human Fas-L mAb. These data suggest that the
      inflammatory response at the margin of colorectal liver metastases induces Fas
      expression in surrounding hepatocytes, allowing them to be killed by Fas-L
      bearing TIL or tumor cells and facilitating the invasion of the tumor into
      surrounding liver tissue.

PMID- 10079248
TI  - Role of macrophage scavenger receptors in hepatic granuloma formation in mice.
AB  - In mice homozygous for the gene mutation for type I and type II macrophage
      scavenger receptors (MSR-A), MSR-A-/-, the formation of hepatic granulomas caused
      by a single intravenous injection of heat-killed Corynebacterium parvum was
      delayed significantly for 10 days after injection, compared with granuloma
      formation in wild-type (MSR-A+/+) mice. In the early stage of granuloma
      formation, numbers of macrophages and their precursor cells were significantly
      reduced in MSR-A-/- mice compared with MSR-A+/+ mice. In contrast to MSR-A+/+
      mice, no expression of monocyte chemoattractant protein-1, tumor necrosis factor
      alpha, and interferon-gamma mRNA was observed in MSR-A-/- mice by 3 days after
      injection. Also in MSR-A-/- mice, uptake of C. parvum by Kupffer cells and
      monocyte-derived macrophages in the early stage of granuloma formation was lower
      and elimination of C. parvum from the liver was slower than in MSR-A+/+ mice. In
      the livers of MSR-A+/+ mice, macrophages and sinusoidal endothelial cells
      possessed MSR-A, but this was not seen in the livers of MSR-A-/- mice. In both
      MSR-A-/- and MSR-A+/+ mice, expression of other scavenger receptors was
      demonstrated. These data suggest that MSR-A deficiency impairs the uptake and
      elimination of C. parvum by macrophages and delays hepatic granuloma formation,
      particularly in the early stage.

PMID- 10079249
TI  - Frequent genetic alterations in simple urothelial hyperplasias of the bladder in
      patients with papillary urothelial carcinoma.
AB  - In order to understand the origin of bladder cancer, very early urothelial
      lesions must be investigated in addition to more advanced tumors. Tissue from 31
      biopsies of 12 patients with urothelial hyperplasias and simultaneous or
      consecutive superficial papillary tumors were used to microdissect urothelium
      from 15- microm sections of biopsies. The biopsies were obtained with the
      recently developed highly sensitive diagnostic method of 5-aminolevulinic acid
      induced fluorescence endoscopy (AFE). Besides flat and papillary urothelial
      neoplasms, the method of photodynamic diagnostics also detects simple urothelial
      hyperplasias as fluorescent positive lesions. In addition, 12 fluorescence
      positive biopsies showing histologically normal urothelium were investigated.
      Fluorescence in situ hybridization was done using a dual color staining technique
      of biotinylated centromeric probes of chromosomes 9 and 17 and digoxigenin
      labeled gene-specific P1 probes for chromosomes 9q22 (FACC), 9p21(p16/CDKI2), and
      17p13(p53). Ten of 14 hyperplasias (70%) showed deletions of chromosome 9. In 7
      out of 8 patients with genetic alterations in the hyperplasias the genetic change
      was also present in the papillary tumor. Six out of 12 samples of microdissected
      normal urothelium also showed genetic alterations on chromosome 9.
      Microdissection of urothelial lesions, obtained during AFE, has led to the first
      unequivocal documentation of genetic changes in urothelial lesions diagnosed as
      normal in histopathology. Thus, this technical approach is important to provide
      insight into the earliest molecular alterations in bladder carcinogenesis.

PMID- 10079250
TI  - Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in
      both soft tissue and bone.
AB  - Trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. The
      presence of these trisomies in related benign fibrous lesions of bone has not
      been previously addressed. In this study, 22 specimens from 19 patients diagnosed
      with desmoid tumor, desmoplastic fibroma, periosteal desmoid tumor, osteofibrous
      dysplasia, or fibrous dysplasia were examined by cytogenetic analysis of short
      term cultures and bi-color fluorescence in situ hybridization of cytological
      touch preparations or paraffin-embedded tissue with centromeric probes for
      chromosomes 8 and 20. Trisomy 8 and trisomy 20 were detected by molecular
      cytogenetic methodologies in 15 specimens, including 10 primary bone lesions.
      Traditional cytogenetic analysis revealed trisomy 8 in two cases of osteofibrous
      dysplasia. Our findings demonstrate that trisomy 8 and trisomy 20 are also
      nonrandom aberrations in histologically similar, but clinically distinct, benign
      fibrous lesions of bone.

PMID- 10079251
TI  - Murine cytomegalovirus immediate-early promoter directs astrocyte-specific
      expression in transgenic mice.
AB  - Murine cytomegalovirus (MCMV), which causes acute, latent, and persistent
      infection of the natural host, is used as an animal model of human
      cytomegalovirus (HCMV) infection. Transcription of MCMV immediate-early (IE)
      genes is required for expression of the early and late genes and is dependent on
      host cell transcription factors. Cell-type-specific expression activity of the
      MCMV IE promoter was analyzed in transgenic mice generated with the major IE
      (MIE) enhancer/promoter involving nucleotides -1343 to -6 (1338 bp) connected to
      the reporter gene lacZ. Distinct expression was observed in the brain, kidneys,
      stomach, and skeletal muscles. Weak expression was observed in a portion of the
      parenchymal cells of the salivary glands and pancreas, and expression was hardly
      detected in the lungs, intestine, or immune and hematopoietic organs such as the
      thymus, spleen, lymph nodes, and bone marrow. The spectrum of organs positive for
      expression was narrower than that of the HCMV MIE promoter-lacZ transgenic mice
      reported previously and showed a greater degree of cell-type specificity.
      Interestingly, astrocyte-specific expression of the transgene was observed in the
      brain and primary glial cultures from the transgenic mice by combination of beta
      galactosidase (beta-Gal) expression and immunostaining for cell markers. However,
      the transgene was not expressed in neurons, oligodendroglia, microglia, or
      endothelial cells. Furthermore, the beta-Gal expression in glial cultures was
      stimulated significantly by MCMV infection or by addition of calcium ionophore.
      These observations indicated that expression activity of the MCMV IE promoter is
      strictly cell-type specific, especially astrocyte-specific in the brain. This
      specific pattern of activity is similar to that of natural HCMV infection in
      humans.

PMID- 10079252
TI  - Down-regulation of HLA class I antigen-processing molecules in malignant
      melanoma: association with disease progression.
AB  - Expression of the proteasome subunits LMP2 and LMP7, the MHC-encoded transporter
      subunits TAP1 and TAP2, and HLA Class I antigens was examined by immunoperoxidase
      staining in 10 nevi and 98 melanoma lesions (60 primary and 38 metastatic),
      because these molecules play an important role in the presentation of melanoma
      associated peptide antigens to cytotoxic T cells. LMP2 was less frequently
      expressed than LMP7 in primary and metastatic melanoma lesions. TAP1, TAP2, and
      HLA Class I antigen expression was more frequently (P < 0.05) down-regulated in
      metastatic than in primary melanoma lesions and in nevi. A synchronous TAP1,
      TAP2, and HLA Class I antigen down-regulation was observed in 58% of primary and
      52% of metastatic lesions. TAP and HLA Class I antigen down-regulation in primary
      lesions was significantly associated with lesion thickness, stage of disease,
      reduced time to disease progression, and reduced survival. These results suggest
      that TAP down-regulation plays a role in the clinical course of malignant
      melanoma, probably by providing melanoma cells with a mechanism to escape from
      cytotoxic T lymphocyte recognition during disease progression.

PMID- 10079253
TI  - Urinary bladder transitional cell carcinogenesis is associated with down
      regulation of NF1 tumor suppressor gene in vivo and in vitro.
AB  - The NF1 gene product (neurofibromin) is known to act as a tumor suppressor
      protein by inactivating ras. The best documented factors involved in urinary
      bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and
      p53 suppressor gene mutations. This is the first study reporting alterations in
      NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29
      surgical urinary bladder TCC specimens representing grades 1 to 3 and in three
      cell lines, RT4, 5637, and T24 (representing grades 1 to 3, respectively).
      Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as
      estimated by immunohistochemistry, the decrease being more pronounced in high
      grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with
      adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade
      3 TCC. Immunohistochemistry and Western blotting demonstrated that TCC cell lines
      expressed NF1 protein at different levels, expression being almost undetectable
      in T24 (grade 3) cells. Northern blotting for cell lines demonstrated reduced NF1
      mRNA levels in grade 3 TCC cells. Reverse transcription polymerase chain reaction
      for cell lines and selected grade 2 and grade 3 tissue samples demonstrated NF1
      type II mRNA isoform predominance in all samples studied. Our results show that
      both NF1 mRNA and protein levels are decreased in high-grade TCC, suggesting that
      alterations of NF1 gene expression may be involved in bladder TCC carcinogenesis.

PMID- 10079254
TI  - Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl
      2 family of proteins.
AB  - Analyses of apoptosis and of the apoptosis regulatory proteins Bcl-2, Bax, Bcl-X,
      and Bad were done in 95 nontumorous and neoplastic pituitary tissues by terminal
      deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL),
      immunohistochemistry, and Western blotting. The apoptotic index was relatively
      low in all groups but was at least fourfold higher in pituitary carcinomas
      compared with any other groups. Pituitaries from pregnant and postpartum women
      had a fivefold higher apoptotic index compared with matched controls from
      nonpregnant females. Preoperative treatment of adenomas with octreotide or
      dopamine agonists did not change the apoptotic index significantly. The lowest
      levels of Bcl-2, Bax, and Bcl-X expression were in pituitary carcinomas as
      detected by immunostaining. An immortalized human pituitary adenoma cell line,
      HP75, developed in our laboratory using a replication-defective recombinant human
      adenovirus with an early large T-antigen, had a much higher level of apoptosis
      than nontumorous and neoplastic pituitaries. Treatment with transforming growth
      factor (TGF)-beta1 and protein kinase C (PKC) inhibitors increased apoptosis in
      this cell line. Analysis of the Bcl-2 family of proteins after treatment with TGF
      beta1 and PKC inhibitors showed a 20% to 30% decrease in Bcl-X in the treated
      groups compared with controls. These results, which represent the first study of
      apoptosis in pituitaries from pregnant and postpartum cases and in pituitary
      carcinomas, indicate that 1) the apoptotic rate is low in nontumorous and
      neoplastic pituitary tissues but is relatively higher in pituitary carcinomas, 2)
      there are alterations in the expression of the Bcl-2 family of proteins in
      pituitary neoplasms with a decrease in Bcl-2 expression in pituitary carcinomas
      that may contribute to pituitary tumor pathogenesis and/or proliferation, and 3)
      cultured pituitary tumor cells respond to TGF-beta1 and PKC inhibitors by
      undergoing apoptotic cell death.

PMID- 10079255
TI  - Colonization of in vitro-formed cervical human papillomavirus- associated
      (pre)neoplastic lesions with dendritic cells: role of granulocyte/macrophage
      colony-stimulating factor.
AB  - The purpose of this study was to investigate the ability of CD1a+
      Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)
      associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in
      the presence of keratinocytes derived from normal cervix and HPV-transformed cell
      lines was evaluated in Boyden chambers and in organotypic cultures and correlated
      with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the
      cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes
      contained lower amounts of GM-CSF and induced a decreased motile response of
      LCs/DCs in the Boyden chamber assay compared with those of normal cervical
      keratinocytes. The migration of LCs/DCs in the presence of conditioned media from
      normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the
      migration of LCs/DCs in the presence of conditioned media from HPV-transformed
      keratinocytes could be increased by supplementing the media with recombinant GM
      CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs
      into organotypic cultures of HPV-transformed keratinocytes, as the infiltration
      of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under
      basal conditions and dramatically increased after the addition of GM-CSF to the
      cultures. These results suggest that GM-CSF could play an important role in the
      recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical
      epithelium and be useful as a new immunotherapeutic approach for cervical
      (pre)cancers.

PMID- 10079256
TI  - Human ligands of the Notch receptor.
AB  - During development, the Notch signaling pathway is essential for the appropriate
      differentiation of many cell types in organisms across the phylogenetic scale,
      including humans. Notch signaling is also implicated in human diseases, including
      a leukemia and two hereditary syndromes known as Alagille and CADASIL. To
      generate tools for pursuing the role of the Notch pathway in human disease and
      development, we have cloned and analyzed the expression of three human homologues
      of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2),
      and human Delta1 (H-Delta-1), and determined their chromosomal localizations. We
      have also raised antibodies to HJ1, and used these antibodies in conjunction with
      in situ hybridization to examine the expression of these ligands in normal and
      cancerous cervical tissue. We find that, as reported previously for Notch, the
      ligands are up-regulated in certain neoplastic tissues. This observation is
      consistent with the notion that Notch signaling is an important element in these
      pathogenic conditions, raising the possibility that modulation of Notch activity
      could be used to influence the fate of the cells and offering a conceivable
      therapeutic avenue.

PMID- 10079257
TI  - Ki-A10, a germ cell nuclear antigen retained in a subset of germ cell-derived
      tumors.
AB  - Monoclonal antibody Ki-A10 recognizes a nuclear antigen of 25 and 22 kd apparent
      molecular mass, which is abundantly expressed by immature gonocytes,
      spermatogonia, and spermatocytes, whereas it is absent in spermatids,
      spermatozoa, oocytes, and normal somatic tissues. In a broad spectrum of human
      cancers the antibody showed no reactivity except for a small subset of malignant
      lymphomas. Because of this restricted expression pattern, we examined 173 germ
      cell tumors and 18 sex cord stromal tumors immunohistochemically to assess the
      distribution of the Ki-A10 antigen. A strongly positive reaction was found in
      classic seminomas, dysgerminomas, spermatocytic seminomas, and the germ cell
      component of gonadoblastomas. Yolk sac tumors presented a heterogeneous
      reactivity pattern ranging from overall positivity to complete lack of antigen
      expression, and in three of eight choriocarcinomas, a few clusters of
      cytotrophoblast cells were strongly labeled. All other tumors, including Leydig
      and Sertoli cell tumors as well as placental tissue, were negative. Our findings
      suggest that specific germ cell antigens can be retained in germ cell tumors
      along particular differentiation pathways. Ki-A10 is the first marker that
      consistently labels spermatocytic seminoma, further confirming its germ cell
      origin and suggesting a close relationship to classic seminoma. The antibody may
      serve for diagnostic purposes and promises new insights into the process of germ
      cell differentiation and the development of germ cell-derived neoplasia.

PMID- 10079259
TI  - Podocalyxin in rat platelets and megakaryocytes.
AB  - Podocalyxin is a membrane protein of rat podocytes and endothelial cells. It has
      not been described in other cell types, and no amino acid or DNA sequence data
      are available about it. Here we show that podocalyxin antigens are present in rat
      platelets and megakaryocytes. In resting platelets, the antigens are mainly
      intracellular but become surface exposed after thrombin stimulation, as shown by
      immunofluorescence and flow cytometry. By Western blotting, platelet podocalyxin
      has an apparent Mr of 140,000. Cytocentrifuge slides of rat bone marrow show that
      anti-podocalyxin antibodies recognize large polyploid cells also expressing
      CD62P, indicating that the cells are megakaryocytes. From a rat glomerular cDNA
      library we isolated a clone covering the carboxyl-terminal nucleotides of rat
      podocalyxin. Its putative transmembrane or intracellular domains are 100% or >93%
      identical, respectively, with the human and rabbit podocalyxin-like proteins. The
      truncated extracellular domain extends to include two of the four conserved
      cysteines shared by podocalyxin-like proteins. By Northern blotting, a 5.5-kb
      renal cortical transcript is seen. By in situ hybridization, cRNA probes
      recognize podocytes, endothelial cells, and megakaryocytes, and by reverse
      transcription polymerase chain reaction, platelets are shown to contain
      podocalyxin mRNA. Our results show that rat podocalyxin is a homologue of the
      previously cloned podocalyxin-like proteins and suggest that also in mammals
      podocalyxin has a role in hematopoiesis, as previously shown in the chicken.

PMID- 10079258
TI  - Splenic marginal zone lymphomas of mice.
AB  - Splenic marginal zone lymphomas (MZLs) have been found to occur at a high
      frequency in NFS.N mice congenic for high-expressing ecotropic murine leukemia
      virus (MuLV) genes from AKR and C58 mice. Based on morphological, immunological,
      and molecular studies of these mice, MZL is clearly recognizable as a distinct
      disease with a characteristic clinical behavior. MZL was staged according to the
      degree of accumulation and morphological change of cells within the splenic
      marginal zone, as follows: 1) a moderate increase in normal-looking MZ cells,
      judged to be prelymphomatous, and 2) MZL in three variants: i) distinct
      enlargement of MZ by normal-looking cells (MZL), ii) distinct enlargement of MZ
      by basophilic centroblast-like cells (MZL+), and iii) extensive splenic
      involvement by centroblast-like cells (MZL++). The rate of mitosis and apoptosis
      increases with lymphoma grade. In most cases, emergence of a dominant IgH clonal
      pattern in paired splenic biopsy and necropsy samples was correlated with
      progression. MZLs were transplantable and homed to the spleen. MZL may constitute
      a commonly occurring lymphoma type unrecognized, in part, because of the
      centroblastic morphology of high-grade MZL and possible overgrowth of lower-grade
      MZL by more aggressive follicular lymphomas.

PMID- 10079260
TI  - Exposure to hyperoxia decreases the expression of vascular endothelial growth
      factor and its receptors in adult rat lungs.
AB  - Exposure to high levels of inspired oxygen leads to respiratory failure and death
      in many animal models. Endothelial cell death is an early finding, before the
      onset of respiratory failure. Vascular endothelial growth factor (VEGF) is highly
      expressed in the lungs of adult animals. In the present study, adult Sprague
      Dawley rats were exposed to >95% FiO2 for 24 or 48 hours. Northern blot analysis
      revealed a marked reduction in VEGF mRNA abundance by 24 hours, which decreased
      to less than 50% of control by 48 hours. In situ hybridization revealed that VEGF
      was highly expressed in distal airway epithelial cells in controls but
      disappeared in the oxygen-exposed animals. Immunohistochemistry and Western blot
      analyses demonstrated that VEGF protein was decreased at 48 hours. TUNEL staining
      demonstrated the presence of apoptotic cells coincident with the decline in VEGF.
      Abundance of VEGF receptor mRNAs (Flt-1 and KDR/Flk) decreased in the late time
      points of the study (48 hours), possibly secondary to the loss of endothelial
      cells. We speculate that VEGF functions as a survival factor in the normal adult
      rat lung, and its loss during hyperoxia contributes to the pathophysiology of
      oxygen-induced lung damage.

PMID- 10079261
TI  - IL-1 up-regulates osteopontin expression in experimental crescentic
      glomerulonephritis in the rat.
AB  - Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to
      promote macrophage infiltration in rat anti-glomerular basement membrane (GBM)
      glomerulonephritis. The present study investigated the role of interleukin-1 (IL
      1) in the up-regulation of renal OPN expression in this disease model.
      Accelerated anti-GBM glomerulonephritis was induced in groups of six rats.
      Animals were treated by a constant infusion of the IL-1 receptor antagonist or
      saline (control) over days -1 to 14 (induction phase) or days 7 to 21
      (established disease). In normal rat kidney, OPN was expressed in a few tubules
      (<5%) and absent from glomeruli. During the development of rat anti-GBM disease
      (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein
      expression in glomeruli (>5 cells per glomerular cross-section) and tubular
      epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was
      associated with macrophage accumulation within the kidney, severe proteinuria,
      loss of renal function, and severe histological damage including glomerular
      crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor
      antagonist treatment of either the induction phase of disease or established
      disease significantly reduced OPN mRNA and protein expression in glomeruli (/75
      85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression
      was associated with significant inhibition of macrophage accumulation and
      progressive renal injury. In vitro, the addition of IL-1 to the normal rat
      tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an
      effect that was dose-dependent and inhibited by the addition of IL-1 receptor
      antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal
      OPN expression. In conclusion, this study provides in vivo and in vitro evidence
      that IL-1 up-regulates OPN expression in experimental kidney disease and support
      for the argument that inhibition of OPN expression is one mechanism by which IL-1
      receptor antagonist treatment suppresses macrophage-mediated renal injury.

PMID- 10079262
TI  - Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts.
AB  - Glutaraldehyde-treated porcine aortic valve xenografts frequently fail due to
      calcification. Calcification in the prostheses begins intracellularly. In a
      previous study, various types of cell injury to canine valvular fibroblasts,
      including glutaraldehyde treatment, led to calcification. An influx of
      extracellular Ca2+ into the phosphate-rich cytosol was theorized to be the
      mechanism of calcification. To test the Ca2+ influx theory, cytosolic Ca2+ and Pi
      concentrations were assessed in glutaraldehyde-treated porcine aortic valve
      fibroblasts, and their relationship to a subsequent calcification was studied.
      Glutaraldehyde caused an immediate and sustained massive cytosolic Ca2+ increase
      that was dose dependent and a several-fold increase in Pi. Calcification of cells
      followed within a week. The earliest calcification was observed in blebs formed
      on glutaraldehyde-treated cells. Live control cells or cells fixed with
      glutaraldehyde in Ca2+-free solution did not calcify under the same conditions.
      Concomitant increases in Ca2+ and Pi in glutaraldehyde-treated cells appear to
      underlie the mechanism of calcification, and the presence of extracellular Ca2+
      during glutaraldehyde fixation promotes calcification.

PMID- 10079263
TI  - Reduced tumor necrosis factor-alpha and transforming growth factor-beta1
      expression in the lungs of inbred mice that fail to develop fibroproliferative
      lesions consequent to asbestos exposure.
AB  - Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta mRNA
      and protein expression and the degree of fibroproliferative response to inhaled
      asbestos fibers are clearly reduced in the 129 inbred mouse strain as compared
      with typical fibrogenesis observed in the C57BL/6 inbred strain. The C57BL/6 mice
      showed prominent lesions at bronchiolar-alveolar duct (BAD) junctions where
      asbestos fibers deposit and responding macrophages accumulate. The 129 mice,
      however, were generally indistinguishable from controls even though the numbers
      of asbestos fibers deposited in the lungs of all exposed animals were the same.
      Quantitative morphometry of H&E-stained lung sections comparing the C57BL/6 and
      129 mice showed significantly less mean cross-sectional area of the BAD junctions
      in the 129 animals, apparent at both 48 hours and 4 weeks after exposure. In
      addition, fewer macrophages had accumulated at these sites in the 129 mice.
      Nuclear bromodeoxyuridine immunostaining demonstrated that the number of
      proliferating cells at first alveolar duct bifurcations and in adjacent terminal
      bronchioles was significantly reduced in the 129 strain compared with C57BL/6
      mice at 48 hours after exposure (P < 0.01). TNF-alpha and TGF-beta1 gene
      expression, as measured by in situ hybridization, was reduced in the 129 mice at
      48 hours after exposure, and expression of TNF-alpha and TGF-beta1 protein, as
      measured by immunohistochemistry, was similarly reduced or absent in the 129
      animals. We postulate that the protection afforded the 129 mice is related to
      reduction of growth factor expression by the bronchiolar-alveolar epithelium and
      lung macrophages.

PMID- 10079264
TI  - Prolactin receptor expression in the developing human prostate and in
      hyperplastic, dysplastic, and neoplastic lesions.
AB  - In situ hybridization and immunohistochemistry were used to localize and compare
      the expression of the long form of the human prolactin receptor in fetal,
      prepubertal, and adult prostate. Results were then compared with hyperplastic,
      dysplastic, and neoplastic lesions. Both receptor message and protein were
      predominately localized in epithelial cells of the fetal, neonatal, prepubertal,
      and normal adult prostate. In hyperplastic lesions the expression of the receptor
      was unchanged with respect to normal epithelial cells. Irrespective of grade,
      markedly enhanced expression of the receptor was evident in dysplastic lesions.
      In lower Gleason grade carcinomas the intensity of receptor signal at the message
      and protein levels approximated that found in normal prostatic epithelium.
      However, in foci within higher grade cancers, receptor expression appeared
      diminished. Results from our study suggest that prolactin action plays a role in
      the development and maintenance of the human prostate and may also participate in
      early neoplastic transformation of the gland. Diminution of receptor expression
      in high grade neoplasms could reflect the emergence of a population of cells that
      are no longer responsive to the peptide hormone.

PMID- 10079265
TI  - The compliance of collagen gels regulates transforming growth factor-beta
      induction of alpha-smooth muscle actin in fibroblasts.
AB  - Wound contraction is mediated by myofibroblasts, specialized fibroblasts that
      appear in large numbers as the wound matures and when resistance to contractile
      forces increases. We considered that the regulation of myofibroblast
      differentiation by wound-healing cytokines may be dependent on the resistance of
      the connective tissue matrix to deformation. We examined transforming growth
      factor-beta1 (TGF-beta1) induction of the putative fibroblast contractile marker,
      alpha-smooth muscle actin (alpha-SMA), and the regulation of this process by the
      compliance of collagen substrates. Cells were cultured in three different types
      of collagen gels with wide variations of mechanical compliance as assessed by
      deformation testing. The resistance to collagen gel deformation determined the
      levels of intracellular tension as shown by staining for actin stress fibers. For
      cells plated on thin films of collagen-coated plastic (ie, minimal compliance and
      maximal intracellular tension), TGF-beta1 (10 ng/ml; 6 days) increased alpha-SMA
      protein content by ninefold as detected by Western blots but did not affect beta
      actin content. Western blots of cells in anchored collagen gels (moderate
      compliance and tension) also showed a TGF-beta1-induced increase of alpha-SMA
      content, but the effect was greatly reduced compared with collagen-coated plastic
      (<3-fold increase). In floating collagen gels (high compliance and low tension),
      there were only minimal differences of alpha-SMA protein. Northern analyses for
      alpha-SMA and beta-actin indicated that TGF-beta1 selectively increased mRNA for
      alpha-SMA similar to the reported protein levels. In pulse-chase experiments,
      [35S]methionine-labeled intracellular alpha-SMA decayed most rapidly in floating
      gels, less rapidly in anchored gels, and not at all in collagen plates after TGF
      beta1 treatment. TGF-beta1 increased alpha2 and beta1 integrin content by 50% in
      cells on collagen plates, but the increase was less marked on anchored gels and
      was undetectable in floating gels. When intracellular tension on collagen
      substrates was reduced by preincubating cells with blocking antibodies to the
      alpha2 and beta1 integrin subunits, TGF-beta1 failed to increase alpha-SMA
      protein content in all three types of collagen matrices. These data indicate that
      TGF-beta1-induced increases of alpha-SMA content are dependent on the resistance
      of the substrate to deformation and that the generation of intracellular tension
      is a central determinant of contractile cytoskeletal gene expression.

PMID- 10079266
TI  - Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the
      invasiveness of cultured keloid fibroblasts.
AB  - Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein
      tyrosine kinases (PTKs) play an important role in the regulation of cell growth
      and differentiation. Activation of PTK cascades in keloid fibroblasts is thought
      to be closely linked to abnormal cell proliferation and migration. We determined
      the expression profile of PTK genes in normal skin and keloid fibroblasts using
      the homology cloning method with a degenerated primer. Eight PTK genes were
      expressed among a total of 46 receptor-type clones. The most abundant type of PTK
      receptors was the platelet-derived growth factor receptor in both fibroblasts.
      However, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in
      keloid-derived fibroblasts (9 of 24). Immunohistochemical analysis confirmed the
      high expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts.
      To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated
      cell proliferation and invasion activities of both types of fibroblasts. The
      mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum
      stimulation. In contrast, the invasive activity of keloid fibroblasts was
      markedly increased in the presence of IGF-I, and inhibited by a neutralizing
      antibody against IGF-IR. Our results indicate the involvement of activated IGF
      I/IGF-IR in the pathogenesis of keloid by enhancing the invasive activity of
      fibroblasts.

PMID- 10079267
TI  - Nature and severity of the glomerular response to nephron reduction is strain
      dependent in mice.
AB  - Nephron reduction is an important factor in the development of
      glomerulosclerosis. In a study of the oligosyndactyly (Os) mutation that causes a
      congenital 50% reduction in nephron number, we previously found that ROP Os/+
      mice developed glomerulosclerosis whereas C57B1/6J Os/+ mice did not. We
      concluded that the predisposition to glomerulosclerosis depended largely on the
      genetic background, the ROP being sclerosis-prone whereas the C57 strain was
      sclerosis-resistant. In the current experiments we asked whether the intensity of
      the sclerotic response to nephron reduction in the ROP strain was related to the
      time at which it occurred, ie, a pre- or post-natal event. We also determined
      whether the absence of lesions in C57 Os/+ mice was caused by a higher threshold
      for the induction of a sclerotic response in C57 mice. We further examined the
      relationship between glomerular hypertrophy and sclerosis. C57 +/+, C57 Os/+, ROP
      +/+, and ROP Os/+ mice were uninephrectomized (NX) at age 10 weeks and followed
      for 8 weeks. We found no sclerotic changes in NX C57 +/+ and C57 Os/+ mice,
      despite a 75% reduction in nephron number in the latter. In contrast, both NX ROP
      +/+ and NX ROP Os/+ mice had glomerulosclerosis, which was more severe in the NX
      ROP Os/+ mice. Examination of extracellular matrix synthesis and degradation at
      the mRNA level revealed that synthesis exceeded degradation in ROP Os/+ mice. The
      lesions in NX ROP +/+ were less severe than in sham-operated ROP/Os mice,
      suggesting that the timing of nephron reduction affected the amplitude of the
      sclerotic response in this strain. Following NX, an increase in glomerular volume
      was found in C57 +/+, ROP +/+, and ROP Os/+ mice. However, NX did not lead to a
      further increase in glomerular volume in C57 Os/+ mice. We make three
      conclusions: 1) sclerosis was more severe in the ROP strain when nephron
      reduction occurred in utero; 2) the absence of glomerulosclerosis in C57 mice was
      not related to a higher threshold for a sclerosis response in this strain; and 3)
      whereas glomerular size continued to increase as nephron number decreased in ROP
      mice, it reached a plateau in C57 mice.

PMID- 10079268
TI  - Role of extracellular matrix and Ras in regulation of glomerular epithelial cell
      proliferation.
AB  - Signals from extracellular matrix (ECM) to growth factor receptors regulate
      glomerular epithelial cell (GEC) proliferation. Epidermal growth factor (EGF),
      basic fibroblast growth factor, hepatocyte growth factor (HGF), or thrombin
      stimulated proliferation of GECs when the cells were adherent to collagen
      matrices, but not plastic substratum. Furthermore, EGF, HGF, or thrombin
      activated p42 mitogen-activated protein (MAP) kinase in collagen-adherent GECs,
      whereas activation was weak in GECs on plastic. To further examine the
      interaction of ECM with the Ras-MAP kinase cascade, GECs were stably transfected
      with a constitutively active Ras mutant (V12Ras). Low or moderate levels of
      V12Ras expression did not affect basal MAP kinase activity but, unlike parental
      GECs, in clones that express V12Ras, EGF was able to induce proliferation and
      activate MAP kinase when these cells were adherent to plastic. In parental and
      V12Ras-transfected GECs, MAP kinase activation was inhibited by cytochalasin D.
      Thus, adhesion of GECs to ECM facilitates proliferation and MAP kinase activation
      by mitogens acting via tyrosine kinase or non-tyrosine kinase receptors.
      Activation of pathway(s) downstream of V12Ras supplants signals from ECM that
      enable proliferation. These signals may involve the actin cytoskeleton.

PMID- 10079269
TI  - Tumor extension and cell proliferation in adenocarcinomas of the lung.
AB  - To elucidate the mechanism of tumor extension in human pulmonary adenocarcinoma,
      we immunohistochemically investigated the expression of cell cycle regulator
      proteins in 54 small adenocarcinomas less than 3 cm in diameter. The Ki-67
      labeling index was significantly higher in the periphery of the tumor nodule than
      in the center. This proliferative potential correlated well with coexpression of
      cdk2 and cyclin A. p27, one of the cdk inhibitors, was highly expressed in normal
      bronchial epithelial cells. Peripherally located tumor cells expressed p27 at an
      intermediate level, but at a higher frequency and level than those in the center.
      Expression of p21 was also predominant in the periphery. Furthermore, the
      expression patterns of p21 and p27 were reciprocal. In vitro kinase assays
      further demonstrated higher cdk2 kinase activity in the periphery. These results
      suggest that: (i) within an emerging extension made up of peripherally located
      tumor cells, their high proliferative potential gradually wanes as their relative
      topographical position becomes more central in the expanding tumor; (ii)
      peripherally located tumor cells maintain their proliferative potential by higher
      cyclin A-cdk2 complex activity; and (iii) intermediate expression of p21/p27 in
      the peripherally located cells promotes higher cyclin A-cdk2 kinase activity,
      whereas high p21/p27 expression in nonneoplastic cells inhibits kinase activity.

PMID- 10079270
TI  - Bone marrow-derived cells are required for the induction of a pulmonary
      inflammatory response mediated by CD40 ligation.
AB  - The expression of inflammatory mediators by various cells following in vitro CD40
      ligation is well known. However, knowledge of the role and interaction with these
      cells in the establishment and maintenance of in vivo immune-mediated
      inflammation is limited. In this report, a chimeric mouse model based on CD40
      knockout and wild-type mice was used to assess the role of bone marrow (BM)
      derived and non-BM-derived cells in a CD40-mediated pulmonary inflammation
      response. CD40+ BM-derived cells were required for initial cell recruitment,
      pulmonary edema, and weight loss associated with this response. The structural
      CD40+ non-BM-derived cells of the lung, such as fibroblasts, epithelial cells,
      and endothelial cells, could not by themselves establish any level of pulmonary
      inflammation. However, both the CD40+ BM-derived cells and the structural CD40+
      non-BM-derived cells of the lung were required to maximize the level of pulmonary
      inflammation. Both B cells and T cells played a contributing role in macrophage
      recruitment and pulmonary edema but neither contributed to the inflammation
      associated weight loss. These experiments indicate that CD40+ BM-derived cells
      were critical to the induction of pulmonary inflammation and that alveolar
      macrophages, B cells, and T cells contributed to selective aspects of the
      response.

PMID- 10079271
TI  - Up-regulated production and activation of the complement system in Alzheimer's
      disease brain.
AB  - We used reverse transcriptase-polymerase chain reaction and Western blotting
      techniques to measure the levels of complement mRNAs and their protein products
      in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r,
      C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain
      that were investigated. The mRNA levels were markedly up-regulated in affected
      areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus,
      which had dense accumulations of plaques and tangles, C1q mRNA was increased 11-
      to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were
      substantially higher than in the livers of the same cases. Western blot analysis
      of AD hippocampus established the presence of all of the native complement
      proteins as well as their activation products C4d, C3d, and the membrane attack
      complex. These data indicate that high levels of complement are being produced in
      affected areas of AD brain, that full activation of the classical complement
      pathway is continuously taking place, and that this activation may be
      contributing significantly to AD pathology.

PMID- 10079273
TI  - Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in
      contrast to leiomyoma.
AB  - Distinction of malignant uterine leiomyosarcomas from benign leiomyomas by
      morphological criteria is not always possible. Leiomyosarcomas typically have
      complex cytogenetic abnormalities; in contrast, leiomyomas have simple or no
      cytogenetic abnormalities. To understand better the biological distinction(s)
      between these tumors, we analyzed two other potential markers of genomic
      instability, loss of heterozygosity (LOH) and microsatellite instability. We
      examined archival materials from 16 leiomyosarcomas and 13 benign leiomyomas by
      polymerase chain reaction for 26 microsatellite polymorphisms. Markers were
      selected based on previous reports of cytogenetic or molecular genetic
      abnormalities in leiomyosarcomas or leiomyomas and surveyed chromosomes 7, 9, 10,
      11, 12, 14, 15, 16, 18, 21, and X. LOH for markers on chromosomes 15, 18, 21, and
      X was infrequent in leiomyosarcomas (1 of 6 tumors for each chromosome) and not
      observed for markers on chromosomes 7, 9, 11, 12, 14, or 16. Interestingly, 8 of
      14 (57.2%) informative leiomyosarcomas had LOH for at least one marker on
      chromosome 10 and involved both chromosomal arms in 45.5% (5 of 11). In contrast
      to leiomyosarcomas, LOH for chromosome 10 was not found in 13 benign leiomyomas.
      Microsatellite instability was found infrequently in leiomyosarcomas and not
      detected in leiomyoma. Clinicopathological features (eg, atypia, necrosis, and
      clinical outcome) did not appear to correlate with LOH for chromosome 10. In
      contrast to other chromosomes studied, LOH on chromosome 10 was frequent in
      leiomyosarcomas and absent in benign leiomyomas.

PMID- 10079274
TI  - Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and
      gastric ulcer in Mongolian gerbils.
AB  - The establishment of persisting Helicobacter pylori infection in laboratory
      animals has been difficult, but in 1996 Hirayama reported the development of a
      successful Mongolian gerbil model. The present study was undertaken with two
      aims: to better characterize the normal histological structure and histochemical
      properties of the gastric mucosa of the Mongolian gerbil; and to evaluate the
      progression of the histopathological features of H. pylori-induced gastritis in
      this animal model for one year after the experimental infection. Seventy-five
      Mongolian gerbils were used. Mongolian gerbils were sacrificed at 2, 4, 8, 12,
      26, 38, and 52 weeks after H. pylori inoculation. Sections prepared from stomachs
      immediately fixed in Carnoy's solution were stained with hematoxylin and eosin
      and Alcian blue at pH 2.5/periodic acid-Schiff, a dual staining consisting of the
      galactose oxidase-cold thionin Schiff reaction and paradoxical Concanavalin A
      staining, and with immunostaining for H. pylori and BrdU. H. pylori infection
      induced in the Mongolian gerbil a chronic active gastritis, in which a marked
      mucosal infiltration of neutrophils on a background of chronic inflammation
      became detectable 4 weeks after inoculation and continued up to 52 weeks.
      Intestinal metaplasia and gastric ulcers appeared after 26 weeks in some of the
      animals, whereas others developed multiple hyperplastic polyps. The Mongolian
      gerbil represents a novel and useful model for the study of H. pylori-induced
      chronic active gastritis and may lend itself to the investigation of the
      epithelial alterations that lead to intestinal metaplasia and gastric neoplasia.

PMID- 10079272
TI  - Early growth response factor-1 induction by injury is triggered by release and
      paracrine activation by fibroblast growth factor-2.
AB  - Cell migration and proliferation that follows injury to the artery wall is
      preceded by signaling and transcriptional events that converge at the promoters
      of multiple genes whose products can influence formation of the neointima.
      Transcription factors, such as early growth response factor-1 (Egr-1), with
      nucleotide recognition elements in the promoters of many pathophysiologically
      relevant genes, are expressed at the endothelial wound edge within minutes of
      injury. The mechanisms underlying the inducible expression of Egr-1 in this
      setting are not clear. Understanding this process would provide important
      mechanistic insights into the earliest events in the response to injury. In this
      report, we demonstrate that fibroblast growth factor-2 (FGF-2) is released by
      injury and that antibodies to FGF-2 almost completely abrogate the activation and
      nuclear accumulation of Egr-1. FGF-2-inducible egr-1-promoter-dependent
      expression is blocked by PD98059, a specific inhibitor of mitogen-activated
      protein kinase/extracellular signal-regulated kinase (ERK)-1/2 (MEK-1/2), as well
      as by dominant negative mutants of ERK-1/2. Inducible ERK phosphorylation after
      injury is dependent on release and stimulation by endogenous FGF-2. Antisense
      oligonucleotides directed at egr-1 mRNA suggest that Egr-1 plays a necessary role
      in endothelial repair after denudation of the monolayer. These findings
      demonstrate that inducible Egr-1 expression after injury is contingent on the
      release and paracrine action of FGF-2.

PMID- 10079275
TI  - In memoriam: julio H. garcia 

PMID- 10079276
TI  - Slow evolutionary rate of GB virus C/hepatitis G virus.
AB  - With the aim of elucidating evolutionary features of GB virus C/hepatitis G virus
      (GBV-C/HGV), molecular evolutionary analyses were conducted using the entire
      coding region of this virus. In particular, the rate of nucleotide substitution
      for this virus was estimated to be less than 9.0 x 10(-6) per site per year,
      which was much slower than those for other RNA viruses. The phylogenetic tree
      reconstructed for GBV-C/HGV, by using GB virus A (GBV-A) as outgroup, indicated
      that there were three major clusters (the HG, GB, and Asian types) in GBV-C/HGV,
      and the divergence between the ancestor of GB- and Asian-type strains and that of
      HG-type strains first took place more than 7000-10,000 years ago. The slow
      evolutionary rate for GBV-C/HGV suggested that this virus cannot escape from the
      immune response of the host by means of producing escape mutants, implying that
      it may have evolved other systems for persistent infection.

PMID- 10079277
TI  - Codon bias and mutability in HIV sequences.
AB  - A survey of the patterns of synonymous codon preference in the HIV env gene
      reveals a correlation between the codon bias and the mutability requirements of
      different regions of the protein. At hypervariable regions in gp120 one finds a
      greater proportion of codons that tend to mutate nonsynonymously, but to a target
      that is similar in hydrophobicity and volume. We argue that this strategy results
      from a compromise between the selective pressure placed on the virus by the
      induced immune response, which favors amino acid substitutions in the
      complementarity determining regions, and the negative selection against missense
      mutations that violate structural constraints of the env protein.

PMID- 10079278
TI  - Synonymous nucleotide divergence and saturation: effects of site-specific
      variations in codon bias and mutation rates.
AB  - The synonymous divergence between Escherichia coli and Salmonella typhimurium is
      explained in a model where there is a large variation between mutation rates at
      different nucleotide sites in the genome. The model is based on the experimental
      observation that spontaneous mutation rates can vary over several orders of
      magnitude at different sites in a gene. Such site-specific variation must be
      taken into account when studying synonymous divergence and will result in an
      apparent saturation below the level expected from an assumption of uniform rates.
      Recently, it has been suggested that codon preference in enterobacteria has a
      very large site-specific variation and that the synonymous divergence between
      different species, e.g., E. coli and Salmonella, is saturated. In the present
      communication it is shown that when site-specific variation in mutation rates is
      introduced, there is no need to invoke assumptions of saturation and a large
      variability in codon preference. The same rate variation will also bring average
      mutation rates as estimated from synonymous sequence divergence into numerical
      agreement with experimental values.

PMID- 10079279
TI  - Archaeabacterial seryl-tRNA synthetases: adaptation to extreme environments and
      evolutionary analysis.
AB  - The aminoacyl-tRNA synthetases are ubiquitous enzymes which catalyze a crucial
      step of the cell life, the specific attachment of amino acids to their cognate
      tRNA. The amino acid sequences of three archaeal seryl-tRNA synthetases (SerRS)
      from Haloarcula marismortui and Methanococcus jannaschii, both belonging to the
      group of Euryarchaeota, and from Sulfolobus solfataricus, of the group of
      Crenarchaeota, were aligned with other eubacterial and eukaryal available SerRS
      sequences. In an attempt to identify some features of adaptation to extreme
      environments of these organisms, amino acid composition and amino acid
      substitutions between mesophilic and thermophilic SerRS were analyzed. In
      addition, universal phylogenetic trees of SerRS including the three known
      archaeal sequences, rooted by the threonyl-tRNA synthetases were inferred. Amino
      acid analyses of the SerRS revealed two ways of adaptation to thermophilic
      environments between the Eubacteria and the Archaea; most of the usually
      described amino acid substitutions were nonsignificant in the case of archaeal
      thermophilic SerRS and most amino acid composition biases seemed to be linked to
      the genome G+C content pressure. The phylogenetic analysis of the SerRS showed
      the Archaea to be paraphyletic, H. marismortui emerging with the Gram-positive
      Bacteria, M. jannaschii being near the root of the tree, and S. solfataricus
      branching with Eucarya.

PMID- 10079280
TI  - Close evolutionary relatedness of alpha-amylases from Archaea and plants.
AB  - The amino acid sequences of 22 alpha-amylases from family 13 of glycosyl
      hydrolases were analyzed with the aim of revealing the evolutionary relationships
      between the archaeal alpha-amylases and their eubacterial and eukaryotic
      counterparts. Two evolutionary distance trees were constructed: (i) the first one
      based on the alignment of extracted best-conserved sequence regions (58 residues)
      comprising beta2, beta3, beta4, beta5, beta7, and beta8 strand segments of the
      catalytic (alpha/beta)8-barrel and a short conserved stretch in domain B
      protruding out of the barrel in the beta3 --> alpha3 loop, and (ii) the second
      one based on the alignment of the substantial continuous part of the
      (alpha/beta)8-barrel involving the entire domain B (consensus length: 386
      residues). With regard to archaeal alpha-amylases, both trees compared brought,
      in fact, the same results; i.e., all family 13 alpha-amylases from domain Archaea
      were clustered with barley pI isozymes, which represent all plant alpha-amylases.
      The enzymes from Bacillus licheniformis and Escherichia coli, representing
      liquefying and cytoplasmic alpha-amylases, respectively, seem to be the further
      closest relatives to archaeal alpha-amylases. This evolutionary relatedness
      clearly reflects the discussed similarities in the amino acid sequences of these
      alpha-amylases, especially in the best-conserved sequence regions. Since the
      results for alpha-amylases belonging to all three domains (Eucarya, Eubacteria,
      Archaea) offered by both evolutionary trees are very similar, it is proposed that
      the investigated conserved sequence regions may indeed constitute the "sequence
      fingerprints" of a given alpha-amylase.

PMID- 10079281
TI  - Nucleotide substitution rate of mammalian mitochondrial genomes.
AB  - We present here for the first time a comprehensive study based on the analysis of
      closely related organisms to provide an accurate determination of the nucleotide
      substitution rate in mammalian mitochondrial genomes. This study examines the
      evolutionary pattern of the different functional mtDNA regions as accurately as
      possible on the grounds of available data, revealing some important "genomic
      laws." The main conclusions can be summarized as follows. (1) High intragenomic
      variability in the evolutionary dynamic of mtDNA was found. The substitution rate
      is strongly dependent on the region considered, and slow- and fast-evolving
      regions can be identified. Nonsynonymous sites, the D-loop central domain, and
      tRNA and rRNA genes evolve much more slowly than synonymous sites and the two
      peripheral D-loop region domains. The synonymous rate is fairly uniform over the
      genome, whereas the rate of nonsynonymous sites depends on functional constraints
      and therefore differs considerably between genes. (2) The commonly accepted
      statement that mtDNA evolves more rapidly than nuclear DNA is valid only for some
      regions, thus it should be referred to specific mitochondrial components. In
      particular, nonsynonymous sites show comparable rates in mitochondrial and
      nuclear genes; synonymous sites and small rRNA evolve about 20 times more rapidly
      and tRNAs about 100 times more rapidly in mitochondria than in their nuclear
      counterpart. (3) A species-specific evolution is particularly evident in the D
      loop region. As the divergence times of the organism pairs under consideration
      are known with sufficient accuracy, absolute nucleotide substitution rates are
      also provided.

PMID- 10079282
TI  - Mitochondrial DNA phylogeny and the evolution of host-plant use in palearctic
      Chrysolina (Coleoptera, Chrysomelidae) leaf beetles.
AB  - The genus Chrysolina consists of specialized phytophagous leaf-beetles
      (Coleoptera, Chrysomelidae) with feed on several plant families. There is no
      explicit phylogenetic hypothesis available for this genus, which includes 65
      subgenera and more than 400 species with a wide distribution. We obtained 839-bp
      sequence data from the 16S rDNA and cytochrome oxidase subunit I (COI)
      mitochondrial genes. Thirty Chrysolina taxa representing eight host-plant
      affiliations, two species of the closely related genus Oreina, and two outgroups
      were sampled. These data sets were used separately and combined to obtain the
      mitochondrial cladogram of the group using maximum-parsimony and maximum
      likelihood criteria. The results were compared to current proposals for
      Chrysolina systematics that are based on morphological, ecological, and
      karyological data. The trees obtained were in the most part congruent with the
      proposed ancestral association of Chrysolina to Lamiaceae based on chromosome
      number in several lineages. A minimum of five host-plant switches from the
      ancestral state inferred at the family level and two at the subclass level
      suggests the absence of parallel evolution of beetles and their host plants.
      Another switch leading to oligophagy at the family level was deduced to have
      occurred in the lineage of the subgenus Chrysolina s.str.

PMID- 10079283
TI  - On the evolution of Dopa decarboxylase (Ddc) and Drosophila systematics.
AB  - We have sequenced most of the coding region of the gene Dopa decarboxylase (Ddc)
      in 24 fruitfly species. The Ddc gene is quite informative about Drosophila
      phylogeny. Several outstanding issues in Drosophila phylogeny are resolved by
      analysis of the Ddc sequences alone or in combination with three other genes,
      Sod, Adh, and Gpdh. The three species groups, melanogaster, obscura, and
      willistoni, are each monophyletic and all three combined form a monophyletic
      group, which corresponds to the subgenus Sophophora. The Sophophora subgenus is
      the sister group to all other Drosophila subgenera (including some named genera,
      previously considered outside the Drosophila genus, namely, Scaptomyza and
      Zaprionus, which are therefore downgraded to the category of subgenus). The
      Hawaiian Drosophila and Scaptomyza are a monophyletic group, which is the sister
      clade to the virilis and repleta groups of the subgenus Drosophila. The subgenus
      Drosophila appears to be paraphyletic, although this is not definitely resolved.
      The two genera Scaptodrosophila and Chymomyza are older than the genus
      Drosophila. The data favor the hypothesis that Chymomyza is older than
      Scaptodrosophila, although this issue is not definitely resolved. Molecular
      evolution is erratic. The rates of nucleotide substitution in 3rd codon position
      relative to positions 1 + 2 vary from one species lineage to another and from
      gene to gene.

PMID- 10079284
TI  - The small-subunit rRNA gene sequences of venerids and the phylogeny of bivalvia.
AB  - The complete nucleotide sequence of the 18S subunit of ribosomal DNA (rDNA) was
      determined for the venerid clams Callista chione (Pitarinae) and Venus verrucosa
      (Venerinae). Comparison of the new sequences with the published sequences of 1
      annelid, 2 gastropods, 2 polyplacophorans, and 19 bivalves showed that when the
      annelids are used as outgroup the gastropods diverge from the bivalves, which
      form a cluster including the polyplacophorans. When the gastropods alone were
      compared with the bivalves, the latter split in two groups corresponding to the
      two subclasses of Heterodonta and Pteriomorpha. The former include two taxa that
      diverged early, Galeomma and Tridacna, while the Veneridae and Mactridae form two
      sister groups. In contrast to previous reports and in line with morphological
      data, the Ostreidae are included in the Pteriomorphia and form a monophyletic
      group.

PMID- 10079285
TI  - Evolution of tandemly repeated sequences: What happens at the end of an array?
AB  - Tandemly repeated sequences are a major component of the eukaryotic genome.
      Although the general characteristics of tandem repeats have been well documented,
      the processes involved in their origin and maintenance remain unknown. In this
      study, a region on the paternal sex ratio (PSR) chromosome was analyzed to
      investigate the mechanisms of tandem repeat evolution. The region contains a
      junction between a tandem array of PSR2 repeats and a copy of the retrotransposon
      NATE, with other dispersed repeats (putative mobile elements) on the other side
      of the element. Little similarity was detected between the sequence of PSR2 and
      the region of NATE flanking the array, indicating that the PSR2 repeat did not
      originate from the underlying NATE sequence. However, a short region of sequence
      similarity (11/15 bp) and an inverted region of sequence identity (8 bp) are
      present on either side of the junction. These short sequences may have
      facilitated nonhomologous recombination between NATE and PSR2, resulting in the
      formation of the junction. Adjacent to the junction, the three most terminal
      repeats in the PSR2 array exhibited a higher sequence divergence relative to
      internal repeats, which is consistent with a theoretical prediction of the
      unequal exchange model for tandem repeat evolution. Other NATE insertion sites
      were characterized which show proximity to both tandem repeats and complex DNAs
      containing additional dispersed repeats. An "accretion model" is proposed to
      account for this association by the accumulation of mobile elements at the ends
      of tandem arrays and into "islands" within arrays. Mobile elements inserting into
      arrays will tend to migrate into islands and to array ends, due to the turnover
      in the number of intervening repeats.

PMID- 10079286
TI  - Identification of new members of the GS ADP-forming family from the de novo
      purine biosynthesis pathway.
AB  - Most living organisms can synthesize isosinate from 5-phosphoribosyl 1
      pyrophosphate in the de novo purine biosynthesis pathway, which is basically
      composed of 10 reaction steps. Phosphoribosylglycinamide synthetase (GARS)
      catalyzes the second step of the pathway. We found that the enzyme shows weak,
      but significant, sequence similarity to phosphoribosylglycinamide
      formyltransferase 2 (GART2) and the ATPase domain of phosphoribosylaminoimidazole
      carboxylase (AIRCA), which catalyze the third and sixth steps of the pathway,
      respectively. In addition, the three enzymes were similar in amino acid sequence
      to biotin carboxylase (BC) and carbamoylphosphate synthetase (CPS), which are the
      members of the GS ADP-forming family. This family has been identified through a
      tertiary structure comparison and includes glutathione synthetase, d-alanine:d
      alanine ligase, BC, succinyl-CoA synthetase beta-chain, and
      phosphoribosylaminoimidazole-succinocarboxamide synthase. Molecular phylogenetic
      analysis based on a multiple alignment of GARS, GART2, AIRCA, BC, and CPS
      suggests that GART2 is more closely related to AIRCA than to GARS among the three
      enzymes from the pathway, though the three enzymes are relatively close to each
      other within the GS ADP-forming family. Moreover, the analysis showed that
      archaeal GARS had diverged before the speciation between bacteria and eucarya.

PMID- 10079287
TI  - Molecular cloning, characterization, and chromosomal localization of the mouse
      homologue of CD84, a member of the CD2 family of cell surface molecules.
AB  - CD84 is a member of the immunoglobulin gene superfamily (IgSF) with two Ig-like
      domains expressed primarily on B lymphocytes and macrophages. Here we describe
      the cloning of the mouse homologue of human CD84. Mouse CD84 cDNA clones were
      isolated from a macrophage library. The nucleotide sequence of mouse CD84 was
      shown to include an open reading frame encoding a putative 329 amino acid protein
      composed of a 21 amino acid leader peptide, two extracellular immunoglobulin (Ig)
      like domains, a hydrophobic transmembrane region, and an 87 amino acid
      cytoplasmic domain. Mouse CD84 shares 57.3% amino acid sequence identity (88.7%,
      considering conservative amino acid substitutions) with the human homologue.
      Chromosome localization studies mapped the mouse CD84 gene to distal chromosome 1
      adjacent to the gene for Ly-9, placing it close to the region where other members
      of the CD2 IgSF (CD48 and 2B4) have been mapped. Northern blot analysis revealed
      that the expression of mouse CD84 was predominantly restricted to hematopoietic
      tissues. Two species of mRNA of 3.6 kilobases (kb) and 1.5 kb were observed. The
      finding that the pattern of expression was restricted to the hematopoietic system
      and the conserved sequence of the mouse CD84 homologue suggests that the function
      of the CD84 glycoprotein may be similar in humans and mice.

PMID- 10079288
TI  - Detection of polymorphism in the RING3 gene by high-throughput fluorescent SSCP
      analysis.
AB  - We describe the use of a high-throughput, fluorescent, polymorphism-detection
      system, based on single-strand conformation polymorphism to screen for
      polymorphism in the RING3 gene. This is the first extensive mutation screen of
      this major histocompatibility complex-linked gene, and the entire coding region
      and intron-exon junctions were examined by multiplexing over 3000 polymerase
      chain reaction products. These techniques should be applicable for analysis of
      variation in other human genes. Investigation of DNA from acute lymphoblastic
      leukemia (ALL) and chronic myeloid leukemia (CML) patients, as well as healthy
      individuals revealed low levels of polymorphism across the RING3 gene. Comparison
      of the distribution of genotypes at each polymorphic site between patients and
      healthy individuals revealed a single site which significantly deviates from
      Hardy-Weinberg proportions.

PMID- 10079289
TI  - Association of the interferon-gamma receptor variant (Val14Met) with systemic
      lupus erythematosus.
AB  - Genetic factors seem to play a significant role in susceptibility to systemic
      lupus erythematosus (SLE). The purpose of this study was to investigate whether
      the amino acid polymorphism (Val14Met) found within the IFN-gamma receptor gene
      (IFNGR1) plays a prominent role in susceptibility to SLE. We found Val14Met
      located at the COOH terminal of the signal peptide of the IFN-gamma receptor.
      There was a significant difference in this polymorphism frequency between SLE
      patients and healthy populations. To clarify whether this amino acid substitution
      resulted in the alteration of the receptor function, we evaluated the induction
      of HLA-DR antigen expression on B cells by IFN-gamma stimulation. There was also
      a significant difference in the induction of HLA-DR by IFN-gamma stimulation
      between B cells. Furthermore, an intracellular cytokine assay indicated that the
      Th1/Th2 balance of Th cells bearing the variant receptor shifted to Th2. The
      genetic polymorphism found within the IFN-gamma receptor gene (Val14Met) may
      result in a shift to Th2, and this shift may increase susceptibility to SLE.

PMID- 10079290
TI  - Codon usage bias and base composition in MHC genes in humans and common
      chimpanzees.
AB  - Codon bias and base composition in major histocompatibility complex (MHC)
      sequences have been studied for both class I and II loci in Homo sapiens and Pan
      troglodytes. There is low to moderate codon bias for the MHC of humans and
      chimpanzees. In the class I loci, the same level of moderate codon bias is seen
      for HLA-B, HLA-C, Patr-A, Patr-B, and Patr-C, while at HLA-A the level of codon
      bias is lower. There is a correlation between codon usage bias and G+C content in
      the A and B loci in humans and chimps, but not at the C locus. To examine the
      effect of diversifying selection on codon bias, we subdivided class I alleles
      into antigen recognition site (ARS) and non-ARS codons. ARS codons had lower bias
      than non-ARS codons. This may indicate that the constraint of codon bias on
      nucleotide substitution may be selected against in ARS codons. At the class II
      loci, there are distinct differences between alpha and beta chain genes with
      respect to codon usage, with the beta chain genes being much more biased. Species
      specific differences in base composition were seen in exon 2 at the DRB1 locus,
      with lower GC content in chimpanzees. Considering the complex evolutionary
      history of MHC genes, the study of codon usage patterns provides us with a better
      understanding of both the evolutionary history of these genes and the evolution
      of synonymous codon usage in genes under natural selection.

PMID- 10079291
TI  - Identification of the gene variations in human CD22.
AB  - CD22, a member of the immunoglobulin superfamily, is a B-cell transmembrane
      glycoprotein that acts as an accessory-signaling component of the B-cell antigen
      receptor (BCR). Recent evidence indicating the role of CD22 as a negative
      regulator of BCR signal transduction prompted us to test the possibility that
      genetic variations of human CD22 may be associated with autoimmune diseases. In
      this study, variation screening of the entire CD22 coding region was performed,
      and possible association with rheumatic diseases was tested, using the genomic
      DNA from 207 healthy Japanese individuals, 68 patients with systemic lupus
      erythematosus (SLE), and 119 patients with rheumatoid arthritis (RA). Through the
      variation screening, seven non-synonymous and four synonymous substitutions were
      identified. In addition, single base substitutions were found in two introns
      flanking exon-intron junctions. Among these variations, Q152E substitution within
      the second extracellular domain was observed with a marginally higher frequency
      in the patients with SLE (3/68, 4.4%) than that in healthy individuals (1/207,
      0.5%) (P=0.048. SLE vs healthy individuals), although this difference was no
      longer significant after correction for the number of comparisons (Pc=0.62). No
      significant association was observed between any of the variations and RA. These
      findings indicate that a number of genetic variants are present in CD22, and
      suggest that CD22 could be considered a candidate for the susceptibility genes to
      autoimmune diseases.

PMID- 10079292
TI  - Role of the interferon-stimulated response element in HLA-B downregulation in
      human melanoma cell lines.
AB  - Tumor cells are thought to escape immune surveillance from T cells by suppressing
      expression of major histocompatibility complex (MHC) class I molecules at their
      cell surface. Human MHC class I molecules are encoded by three different loci
      (HLA-A, -B, and -C). In primary human melanomas as well as melanoma cell lines,
      HLA class I expression is frequently downregulated in a B locus-specific manner.
      To study the involvement of promoter elements in HLA-B locus-specific
      downregulation, a series of reporter constructs containing 5'-flanking sequences
      of the HLA-A2 and -B7 genes were transfected into melanoma cell lines expressing
      high and low levels of HLA-B antigens. It is shown that enhancer A, which is
      generally believed to be a potent enhancer in HLA class I gene transcription,
      only weakly activates transcription in melanoma cell lines. In contrast, the
      interferon-stimulated response element (ISRE), known to induce MHC class I
      expression in response to IFNs, as well as a region comprising site
      alpha/enhancer B significantly stimulate constitutive transcription of HLA class
      I genes. Although none of the promoter elements tested could be demonstrated to
      mediate HLA-B locus-specific downregulation, high and low HLA-B melanoma cell
      lines do differ in ISRE activity as well as in ISRE-binding nuclear factors. The
      finding that high and low HLA-B melanoma cell lines contain different
      transcription factors binding to elements not actively involved in the process of
      HLA-B locus abrogation suggests that these cell lines originate from distinct
      types of melanocyte precursor cells expressing a different set of transcription
      factors.

PMID- 10079293
TI  - Isolation and mapping of the rabbit DM genes.
AB  - Proper peptide presentation by major histocompatibility complex (MHC)-encoded
      class II antigens is dependent on the products of the MHC DM loci. We identified
      the rabbit orthologues (RLA-DMA and -DMB) of human HLA-DMA and -DMB and found
      that they have 76.9% and 78.8% identity with HLA-DMA and -DMB, respectively. Like
      classical class II MHC genes, RLA-DM genes are more closely related to human HLA
      DM genes than to mouse H2-DM. Among the DM family, there is a high degree of
      variability at the amino terminus of the DMa chains, and length variability in
      the cytoplasmic tails of both DMalpha and DMbeta. The rabbit DM genes are
      coexpressed with class II genes in lymphoid tissues, as are the DM genes of other
      mammals. The RLA-DM locus maps to the class II region of the rabbit MHC, and is
      flanked by the DP and DOB loci. Despite having some similarities to class II
      genes of bony fishes, the DM family represents a separate branch of the MHC class
      II family.

PMID- 10079294
TI  - MHC class I genes of the channel catfish: sequence analysis and expression.
AB  - Four cDNAs encoding the major histocompatibility complex (MHC) class I alpha
      chain were isolated from a channel catfish clonal B-cell cDNA library. Sequence
      analysis suggests these cDNAs represent three different MHC class I loci. All
      cDNAs encoded conserved residues characteristic of the MHC class I alpha chain:
      namely, those involved in peptide binding, salt bridges, disulfide bond
      formation, and glycosylation. Southern blot analyses of individual outbred and
      second-generation gynogenetic fish indicated the existence of both polygenic and
      polymorphic loci. Northern blot studies demonstrated that catfish B, T, and
      macrophage cell lines transcribed markedly higher levels of class I alpha and
      beta2-microglobulin (beta2m) mRNA than fibroblast cell lines. In addition,
      immunoprecipitation data showed that a 41 000 Mr glycoprotein (presumably class I
      alpha) was associated with beta2m on the surface of catfish B cells. This latter
      finding is the first direct evidence for the cell surface association of beta2m
      with the MHC class I alpha chain on teleost cells and supports the notion that
      functional MHC class I proteins exist in teleosts.

PMID- 10079295
TI  - Residue 3 of beta2-microglobulin affects binding of class I MHC molecules by the
      W6/32 antibody.
AB  - Previous studies of class I MHC molecules have shown that the owl monkey (Aotus)
      possesses at least two variants of the beta2-microglobulin (beta2m) protein.
      These two variants have different isoelectric points, and exhibit differential
      reactivity with the monoclonal antibody W6/32. We report cDNA sequences of the
      B2m gene, from W6/32-positive and W6/32-negative Aotus cell lines. The two beta2m
      variants we identified exhibit a single amino acid difference at position three.
      An arginine residue at position 3 was correlated with W6/32 reactivity, whereas
      histidine was associated with non-reactivity. W6/32 reactivity was conferred to a
      W6/32-negative Aotus cell line when it was transfected with the B2m from the
      W6/32-positive cell line. Residue 3 of beta2m is located at the surface of the
      class I molecule. It is also close to position 121 of the MHC class I heavy
      chain, which has previously been shown to influence W6/32 antibody binding. We
      conclude that W6/32 binds a compact epitope on the class I molecule that includes
      both residue 3 of beta2m and residue 121 of the heavy chain. We examined the
      distribution of the two beta2m motifs in a sample Aotus population using an
      allele-specific polymerase chain reaction assay. The pattern of beta2m
      segregation we observed matches that which was defined previously by serology.
      Additionally, we identified laboratory-born hybrid animals who possess both
      variants of beta2m.

PMID- 10079296
TI  - Evidence for an additional cattle DQA locus, BoLA-DQA5.
AB  - Studying the genetic polymorphism of the major histocompatibility complex class
      II genes in cattle, we identified an allele (BNI13) which encodes a typical class
      II alpha chain. Its transcription was confirmed by RNA analysis. Sequence
      comparisons, Southern blot, and phylogenetic analyses indicate that (1) BNI13
      represents a distinct DQA locus which we propose to designate BoLA-DQA5, (2) BoLA
      DQA1 and BoLA-DQA5 separated after the divergence of BoLA-DQA1 and BoLA-DQA2, but
      prior to the separation of sheep DQA1 and cattle DQA1, and (3) DQA5 is
      distributed among various cattle breeds but is confined to certain haplotypes.

PMID- 10079297
TI  - Identification of the Tapasin gene in the chicken major histocompatibility
      complex.
AB  - The Tapasin molecule plays a role in the assembly of major histocompatibility
      complex (Mhc) class I molecules in the endoplasmic reticulum, by mediating the
      interaction of class I-beta2-microglobulin dimers with TAP. We report here the
      identification of the Tapasin gene in the chicken Mhc (B complex). This gene is
      located at the centromeric end of the complex, between the class II B-LBI and B
      LBII genes. Like its human counterpart it comprises 8 exons, but features a
      significantly reduced intron size as compared to the human gene. Chicken Tapasin
      codes for a transmembrane protein with a probable endoplasmic reticulum retention
      signal. Exons IV and V, and possibly exon III, code for separate domains that are
      related to the immunoglobulin (Ig) superfamily (this relationship was so far
      unrecognized for human Tapasin domain IV which has lost its two cysteines). Two
      different cDNAs corresponding to the Tapasin gene were isolated, possibly related
      to alternative splicing events; the Ig-like domain encoded by exon IV is missing
      in one of the cDNAs, suggesting either that this domain is not necessary for the
      protein to perform its function, or that the two alternatively spliced cDNAs are
      translated into two functionally different forms of the protein.

PMID- 10079298
TI  - Molecular analysis of an MHC class II deficiency patient reveals a novel mutation
      in the RFX5 gene.
AB  - Patients suffering from major histocompatibility complex (MHC) class II
      deficiency, a rare primary immunodeficiency, are characterized by a lack of MHC
      class II expression which is the result of defects in trans-acting factors. At
      least four complementation groups, A, B, C, and D, can be discerned. The gene
      affected in group C patients is known to be RFX5 and encodes one of the subunits
      of the multimeric phosphoprotein complex, RFX. In the present study we fused
      fibroblasts of a recently identified MHC class II deficiency patient, OSE, with
      fibroblasts derived from patients representative of each of the four
      complementation groups. Transient heterokaryon analysis indicated that OSE
      belonged to complementation group C. Furthermore, transfection of wild-type RFX5
      cDNA into OSE fibroblasts resulted in restoration of the defect. Mutation
      analysis revealed that the RFX5 mRNA lacked four nucleotides and that this
      deletion was the consequence of a G to A transition in a splice acceptor site.
      Genomic oligotyping demonstrated that OSE was homozygous for the splice site
      mutation.

PMID- 10079299
TI  - Diminished recognition of HLA-A2 proteins lacking a cytoplasmic domain (CY) by A2
      restricted, EBV-specific CTLs: possible role of the CY in TAP association.

PMID- 10079300
TI  - Cloning of a cDNA encoding a Pim1 homologue in zebrafish, Danio rerio.

PMID- 10079301
TI  - cDNA cloning, northern hybridization, and mapping analysis of a putative GDS
      related protein gene at the centromeric ends of the human and mouse MHC regions.

PMID- 10079302
TI  - Alternate splice variants of the hemochromatosis gene Hfe.

PMID- 10079303
TI  - Complete cDNA coding sequence of a new HLA-A3 subtype (A*0304) with a new HLA
      polymorphism at exon 3.

PMID- 10079304
TI  - Evolution of the Mhc class I region: the framework hypothesis.
AB  - A comparison of the major histocompatibility complex (Mhc) region between human
      and mouse highlights both stability and differences. The class II and class III
      regions are orthologous; they probably existed in the ancestor in a similar
      organization and were not subjected to major rearrangement. The class I genes, by
      contrast, are definitely paralogous, having been reorganized several times. As
      long as only class I genes were identified, the class I regions of human and
      mouse were difficult to compare directly. The identification of non-class I genes
      has allowed a comparative map to be drawn, which shows that the class I region is
      orthologous between human and mouse as well. The lack of orthology specifically
      applies to the class I sequences. However, the comparative map shows that the non
      orthologous class I sequences occupy homologous locations with regard to the
      conserved genes. I propose a model to explain this paradox. The conserved genes
      may represent samples of a dense "framework" of genes whose alterations are
      deleterious. The homologous positions occupied by class I genes would thus
      represent the few permissive places allowing major perturbations. The evolution
      of the class I sequences, by duplication and deletion, independently in the two
      species, has taken place within the scope defined by the framework: insertion at
      the permissive places, and expansion by creation of class I-related DNA by
      duplication, thus pushing back the boundaries of the framework.

PMID- 10079305
TI  - Sixth international workshop on MHC evolution 

PMID- 10079306
TI  - The present role of bone marrow scintigraphy.

PMID- 10079307
TI  - In vivo evaluation in mice and metabolism in blood of human volunteers of
      [123I]iodo-PK11195: a possible single-photon emission tomography tracer for
      visualization of inflammation.
AB  - We report the in vivo evaluation (biodistribution, displacement and
      metabolization in blood, brain and heart) in mice and the metabolism in blood of
      human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl
      propyl)-3-isoquinoline carboxamide ([123I]iodo-PK11195), a potential radioligand
      for visualization of inflammation in humans by single-photon emission tomography.
      In three series of 18 white mice (NMRI, 20-25 g), the concentration of
      radioactivity was measured during 48 h. Blood samples were taken, organs and
      intestines were excised, excretion was collected and all tissues were weighed and
      counted for radioactivity. The tissue uptake of radioactivity was measured as %
      of the injected activity/g of tissue. The excretion was expressed as % of the
      injected activity. Selective tissue uptake was investigated by pretreatment of
      another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There
      was an inflow of [123I]iodo-PK11195 in the brain and among peripheral organs,
      heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After
      pretreatment with cold PK11195, there was a decrease in accumulation in the
      latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%).
      Metabolite analysis was performed using high-performance liquid chromatography
      (HPLC). First, the extraction yield of [123I]iodo-PK11195 from blood and tissue
      was assessed, and found to be >90%. From blank blood samples and organs spiked
      with [123I]iodo-PK11195 it was concluded that no metabolization took place during
      the extraction procedure. Analysis of plasma, brain and heart of mice showed that
      10 min p.i. [123I]iodo-PK11195 was the only significant (ca. 95%) radioactive
      compound in brain and heart where-as in plasma other radioactive products (>60%)
      appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37
      and 50 min p.i. showed that [123I]iodo-PK11195 rapidly decomposes into two polar
      metabolites, which at these time points accounted for, respectively 31%, 62%, 75%
      and 77% of the total activity.

PMID- 10079308
TI  - Three-dimensional contour detection of left ventricular myocardium using elastic
      surfaces.
AB  - Since the human heart has a complex anatomy, the two-dimensional analysis of
      myocardial scintigrams obviously is not satisfactory. Three-dimensional display
      can be more easily read by clinicians and depicts more accurately tracer
      accumulation defects. In this study we propose a three-dimensional myocardial
      contour detection approach using elastic surfaces. After manual reorientation
      into short-axis slices and transformation into heart coordinates, the myocardial
      mid-wall surface passing through the radial activity mass points is calculated
      using a second-order partial differential equation as a mathematical model.
      Special considerations are implemented to demarcate organs close to the heart. In
      a total of 1102 myocardial scintigrams the three-dimensional contour detection
      calculated a reasonable shape of the left ventricular myocardium in all cases.
      Even in areas with severe myocardial infarction, this approach was able to bridge
      tracer accumulation defects. Inter- and intra-observer variability tests
      confirmed a high reproducibility and user independence. In conclusion, in this
      study the proposed three-dimensional contour detection of left ventricular
      myocardium using elastic surfaces was found to be fast, user-independent and
      reliable, leading to realistic three-dimensional parametric images of myocardial
      scintigrams that even clinicians not experienced in nuclear cardiology can easily
      read.

PMID- 10079309
TI  - Early detection of the no-reflow phenomenon in reperfused acute myocardial
      infarction using technetium-99m tetrofosmin imaging.
AB  - Evaluation of myocardial perfusion in the early stage of acute myocardial
      infarction (MI) is clinically important for adjunctive therapies to minimize
      infarct size. To determine the role of early scintigraphic detection of impaired
      myocardial reperfusion after primary coronary angioplasty (PTCA) in patients with
      acute MI, semiquantitative technetium-99m tetrofosmin single-photon emission
      tomographic (SPET) imaging was performed before primary PTCA (before; area at
      risk), 60 min after PTCA (after) and at 1 month (1 M; final infarct) in 35
      patients with acute MI. The left ventricle was divided into 13 segments and the
      defect score was calculated as the sum of the perfusion defect of each segment,
      from 3 (complete defect) to 0 (normal perfusion). A significant myocardial
      perfusion change after PTCA was defined as a change in the defect score (before
      minus after PTCA) of >/=4. The echocardiographic asynergic score was defined as
      the number of asynergic (severe hypokinetic or akinetic) segments corresponding
      to the analogous segments on SPET images, and recovery of wall motion was
      calculated as absolute change in the asynergic score (before PTCA minus 1 M).
      Among the 35 patients, 15 (43%) had a change in the defect score of <4 (no
      reflow: group 1) while 20 had a change in the defect score of >/=4 (reflow: group
      2). There were no significant differences between the two groups with respect to
      the time between admission to PTCA, revascularization time, collateral grade or
      Thrombolysis in Myocardial Infarction (TIMI) flow grade before PTCA. Despite the
      lack of a difference in area at risk between the two groups (group 1 = 12.8+/-4.3
      and group 2 = 15.1+/-4.7), final infarct size in group 1 was significantly larger
      compared with that in group 2 (8.1+/-4.3 vs 4.9+/-3.0, P<0.001). Recovery of wall
      motion was significantly smaller in group 1 than in group 2 (4.3+/-1.7 to 3.5+/
      1.5 vs 4. 1+/-2.1 to 1.6+/-1.6, P<0.001). In conclusion, a small change (<4) in
      defect score (scintigraphic no-reflow phenomenon) after primary PTCA indicates
      persisting impaired myocardial perfusion or irreversible cellular damage just
      after PTCA which is associated with poor recovery of wall motion, as compared
      with that observed in cases of reflow (>/=4 in defect score).

PMID- 10079310
TI  - Scintigraphic detection of post-pneumonectomy bronchopleural fistulae.
AB  - A total of 20 ventilation studies [16 with xenon-133 and four with technetium-99m
      diethylenetriamine pentaacetic acid (DTPA)] were performed in 11 patients with
      suspected post-pneumonectomy bronchopleural fistulae. The findings on the
      ventilation scan were correlated with bronchoscopy, taken as the gold standard
      for purposes of comparison. The sensitivity and specificity for 133Xe scans were
      83% and 100% respectively, while the sensitivity for 99mTc-DTPA aerosol studies
      was poor at 0%. Special techniques for optimal visualization of the fistulae are
      enumerated.

PMID- 10079311
TI  - Does salivary gland scintigraphy predict response to pilocarpine in patients with
      post-radiotherapy xerostomia?
AB  - This study was undertaken to determine whether standard salivary gland
      scintigraphy may be used for the objective assessment of salivary gland
      sialogogues, in particular oral pilocarpine, in the treatment of post
      radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to
      the head and neck region underwent salivary gland scintigraphy with technetium
      99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine
      (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak
      uptake, time to peak uptake and the percentage of activity excreted following
      lemon juice stimulation were calculated. The results were correlated with the
      subjective response as assessed by questionnaire and visual analogue scale. We
      found no correlation between subjective response and any of the four scan
      parameters analysed. We could not identify any parameter that predicted those
      patients who would respond to pilocarpine. In addition, only one parameter, the
      percentage of activity excreted following stimulation, correlated with previous
      dose of radiotherapy to the gland. In conclusion, in this study salivary gland
      scintigraphy did not appear to correlate with or predict response to oral
      pilocarpine. However, future studies might consider performing salivary gland
      scintigraphy prior to radiotherapy as well as at differing time points following
      the commencement of pilocarpine.

PMID- 10079312
TI  - Optimal scan time for fluorine-18 fluorodeoxyglucose positron emission tomography
      in breast cancer.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has proven
      useful in the differentiation of various tumour entities, including breast
      cancer. In patients with primary breast cancer we performed a 3-h imaging
      protocol to examine possible improvements in tumour detectability and image
      contrast. Twenty-nine patients with primary breast cancer with a diameter of >/=2
      cm that was demonstrated to be malignant by biopsy or surgery were injected with
      370-740 MBq 18F-FDG and scanned in the prone position. Data were acquired 0-40
      min, 1.5 h and 3.0 h after injection. After correction for measured attenuation,
      decay and scatter and iterative reconstruction, standardised uptake values (SUVs)
      and tumour-to-non-tumour and tumour-to-organ ratios were calculated. Visual
      analysis was performed using transverse, sagittal and coronal slices as well as
      3D reprojection images. Tumour-to-non-tumour and tumour-to-organ ratios were
      significantly higher for the 3-h images than for the 1.5-h images. SUVs did not
      increase to the same extent. Lesion detectability was 83% in 1.5-h images
      compared to 93% in 3-h images. We conclude that tumour contrast in breast cancer
      is improved by starting the PET acquisition at 3 h p.i. rather than at 1.5 h p.i.

PMID- 10079313
TI  - Positron emission tomography of murine liver metastases and the effects of
      treatment by combretastatin A-4.
AB  - There are major potential advantages in non-invasive measurement of preclinical
      tumour biology and therapeutic response in clinically relevant, internal body
      sites, notably the ability to follow outcome in individual animals rather than
      averaging results from groups. We have exploited positron emission tomography
      (PET) to determine the feasibility of detecting liver metastases in B6D2F1 mice
      using fluorine-18 fluorodeoxyglucose ([18F]FDG) both before and after treatment
      by the novel cytotoxic agent, combretastatin A-4. The normal distribution of
      [18F]FDG in the absence of disease was characterised, with the clear delineation
      of the brain, the heart and the urinary bladder in all studies. In untreated mice
      with liver metastases, a strong correlation (r2 = 0.98) was found between the
      quantitative estimates of [18F]FDG uptake obtained by analysis of PET images, and
      those obtained from ex vivo assay of liver plus metastases excised immediately
      after imaging. In this first series, the effective limit of resolution was in
      livers containing a number of small metastases (range 8-14) with a single volume
      equivalent of approximately 200 mm3. PET image analysis was concordant with
      histological measurements in showing that single intraperitoneal doses of
      combretastatin A-4 resulted in an average 30% volume destruction of metastatic
      mass by 24 h following administration.

PMID- 10079314
TI  - Regional cerebral blood flow single-photon emission tomography with 99mTc-HMPAO
      and the acetazolamide test in the evaluation of vascular and Alzheimer's
      dementia.
AB  - The diagnostic potential of technetium-99m hexamethylpropylene amine oxime
      (HMPAO) following systemic administration of the cerebral vasodilator
      acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow
      (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer's
      disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study
      was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated
      with 99mTc-HMPAO following systemic administration of acetazolamide.
      Reconstructed SPET slices were evaluated visually and semiquantitatively by a
      semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral
      hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of
      the VD patients and in 70% (23/33) of the AD patients. The corresponding data
      obtained by quantitative evaluation were 41% (7/17) and 71% (15/21),
      respectively. The vascular reserve capacity, as determined with the acetazolamide
      test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of
      the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The
      differences in the perfusion patterns between the VD and AD patients were
      statistically significant (P<0.01, Fischer's exact test). Of the VD patients with
      hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation)
      and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity
      as determined with the acetazolamide test. In the AD group of patients the
      corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the
      acetazolamide test is promising in rCBF SPET to differentiate VD from AD.

PMID- 10079315
TI  - Quantification of cerebral blood flow using technetium-99m ethyl cysteinate dimer
      and single-photon emission tomography.
AB  - The aim of this study was to develop a new method for quantifying regional
      cerebral blood flow (rCBF) with technetium-99m ethyl cysteinate dimer (ECD) and
      single-photon emission tomography (SPET). Employing a three-compartment model, we
      introduced a parameter, regional brain fractionation index (BFI), that reflects
      rCBF values and is obtained by a single SPET scan at optimum time T (min) after
      tracer injection and the integral of arterial input. By analysing the dynamic
      SPET and arterial blood sampling data of 15 subjects, including the results of
      acetazolamide challenges, with the graphical plot method, optimum time T was
      determined to be approximately 20 min post injection. Regional BFI values of each
      subject were calculated from the single SPET data at 20 min and arterial input.
      The relationship between the values of regional BFI and rCBF obtained by xenon
      133 inhalation SPET was analysed by approximation with an exponential function,
      resulting in good agreement (r = 0.907). In the present method, rCBF values were
      determined from regional BFI values by using the inverse exponential function as
      a non-linear regression curve. To validate the method, we applied it to six other
      subjects, in whom acetazolamide challenges were also performed. In comparing rCBF
      values thus obtained and those obtained by 133Xe inhalation SPET, we found a good
      correlation (r = 0.901) with an inclination approximating 1 (= 1.02) and without
      underestimation of rCBF in the high-flow range. Since the present method does not
      require dynamic planar imaging or dynamic SPET scanning, it can be applied to any
      type of SPET scanner and is useful in clinical SPET studies.

PMID- 10079316
TI  - Perfusion impairments in infantile autism on technetium-99m ethyl cysteinate
      dimer brain single-photon emission tomography: comparison with findings on
      magnetic resonance imaging.
AB  - The neuro-anatomical substrate of autism has been the subject of detailed
      investigation. Because previous studies have not demonstrated consistent and
      specific neuro-imaging findings in autism and most such studies have been
      performed in adults and school-aged children, we performed a retrospective review
      in young children in search of common functional and anatomical abnormalities
      with brain single-photon emission tomography (SPET) using technetium-99m ethyl
      cysteinate dimer (ECD) and correlative magnetic resonance imaging (MRI). The
      patient population was composed of 23 children aged 28-92 months (mean: 54
      months) who met the diagnostic criteria of autism as defined in the DSM-IV and
      CARS. Brain SPET was performed after intravenous injection of 185-370 MBq of
      99mTc-ECD using a brain-dedicated annular crystal gamma camera. MRI was performed
      in all patients, including T1, T2 axial and T1 sagittal sequences. SPET data were
      assessed visually. Twenty patients had abnormal SPET scans revealing focal areas
      of decreased perfusion. Decreased perfusion of the cerebellar hemisphere (20/23),
      thalami (19/23), basal ganglia (5/23) and posterior parietal (10/23) and temporal
      (7/23) areas were noted on brain SPET. By contrast all patients had normal MRI
      findings without evidence of abnormalities of the cerebellar vermis, cerebellar
      hemisphere, thalami, basal ganglia or parietotemporal cortex. In conclusion,
      extensive perfusion impairments involving the cerebellum, thalami and parietal
      cortex were found in this study. SPET may be more sensitive in reflecting the
      pathophysiology of autism than MRI. However, further studies are necessary to
      determine the significance of thalamic and parietal perfusion impairment in
      autism.

PMID- 10079317
TI  - Evaluation of dysthymic disorder with technetium-99 m hexamethylpropylene amine
      oxime brain single-photon emission tomography.
AB  - Dysthymic disorder is a chronic disorder characterised by the presence of a
      depressed mood and is classified as a distinct category in DSM-IV, separately
      from major depression. Although brain imaging studies have been performed in
      major depressive disease, there have to date been no reports of such studies in
      dysthymic disorder. In this study 36 patients with dysthymic disorder were
      compared with 16 normal subjects using technetium-99m hexamethylpropylene amine
      oxime brain single-photon emission tomography. A relative blood flow ratio was
      calculated for each region of interest using the average tissue activity in the
      region divided by activity in the cerebellum. There were significant differences
      in the bilateral inferior frontal, bilateral parietal, right superior frontal and
      left posterior temporal regions in the patients with dysthymic disorder compared
      with the healthy controls. These findings support the hypothesis that the
      biological bases for dysthymic disorder and major depression are similar.
      Recognition of these regional abnormalities may have clinical utility in both the
      diagnosis and the treatment of dysthymic disorder. Further studies are needed to
      confirm our results and to assess the influence of treatment in patients with
      dysthymic disorder.

PMID- 10079318
TI  - Measurement of temporal regional cerebral perfusion with single-photon emission
      tomography predicts rate of decline in language function and survival in early
      Alzheimer's disease.
AB  - We determined the relationship between regional cerebral blood flow (rCBF)
      measured with single-photon emission tomography (SPET) and decline in cognitive
      function and survival in Alzheimer's disease. In a prospective follow-up study,
      69 consecutively referred patients with early probable Alzheimer's disease
      (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis
      using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological
      function was assessed at baseline and after 6 months and survival data were
      available on all patients, extending to 5.5 years of follow-up. Lower left
      temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically
      significantly related to decline in language function after 6 months. The
      association between left temporal rCBF and survival was also statistically
      significant (P<0.05) using Cox proportional hazards regression analysis.
      Performing analysis with quartiles of the distribution, we found a threshold
      effect for low left temporal rCBF (rCBF<73.7%, P<0. 01) and high risk of
      mortality. In this lowest quartile, median survival time was 2.7 years (follow-up
      to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5
      years). Kaplan-Meier survival curves showed statistically significant (P<0. 05,
      log rank test) survival curves for the lowest versus other quartiles of left
      temporal rCBF. All results were unaffected by adjustment for age, sex, dementia
      severity, duration of symptoms, education and ratings of local cortical atrophy.
      We conclude that left temporal rCBF predicts decline in language function and
      survival in patients with early probable Alzheimer's disease, with a threshold
      effect of low rCBF and high risk of mortality.

PMID- 10079319
TI  - A deconvolution technique for processing small intestinal transit data.
AB  - The deconvolution technique can be used to compute small intestinal impulse
      response curves from scintigraphic data. Previously suggested approaches,
      however, are sensitive to noise from the data. We investigated whether
      deconvolution based on a new simple iterative convolving technique can be
      recommended. Eight healthy volunteers ingested a meal that contained indium-111
      diethylene triamine penta-acetic acid labelled water and technetium-99m stannous
      colloid labelled omelette. Imaging was performed at 30-min intervals until all
      radioactivity was located in the colon. A Fermi function=(1+e-alphabeta)/(1+e(t
      alpha)beta) was chosen to characterize the small intestinal impulse response
      function. By changing only two parameters, alpha and beta, it is possible to
      obtain configurations from nearly a square function to nearly a monoexponential
      function. Small intestinal input function was obtained from the gastric emptying
      curve and convolved with the Fermi function. The sum of least squares was used to
      find alpha and beta yielding the best fit of the convolved curve to the observed
      small intestinal time-activity curve. Finally, a small intestinal mean transit
      time was calculated from the Fermi function referred to. In all cases, we found
      an excellent fit of the convolved curve to the observed small intestinal time
      activity curve, that is the Fermi function reflected the small intestinal impulse
      response curve. Small intestinal mean transit time of liquid marker (median 2.02
      h) was significantly shorter than that of solid marker (median 2.99 h; P<0.02).
      The iterative convolving technique seems to be an attractive alternative to
      ordinary approaches for the processing of small intestinal transit data.

PMID- 10079320
TI  - Radionuclide therapy practice and facilities in Europe. EANM Radionuclide Therapy
      Committee.

PMID- 10079321
TI  - Visualization of multidrug resistance in vivo.
AB  - Various mechanisms are involved in multidrug resistance (MDR) for
      chemotherapeutic drugs, such as the drug efflux pumps, P-glycoprotein (Pgp) and
      multidrug resistance-associated protein (MRP). In this review the mechanisms
      involved in MDR are described and results are reviewed with particular attention
      to the in vivo imaging of Pgp and MRP. Various detection assays provide
      information about the presence of drug efflux pumps at the mRNA and protein
      levels. However, these methods do not yield information about the dynamic
      function of Pgp and MRP in vivo. For the study of Pgp- and MRP-mediated
      transport, single-photon emission tomography (SPET) and positron emission
      tomography (PET) are available. Technetium-99m sestamibi is a substrate for Pgp
      and MRP, and has been used in clinical studies for tumour imaging, and to
      visualize blockade of Pgp-mediated transport after modulation of the Pgp pump.
      Other 99mTc radiopharmaceuticals, such as 99mTc-tetrofosmin and several 99Tc-Q
      complexes, are also substrates for Pgp, but to date only results from in vitro
      and animal studies are available for these compounds. Several agents, including
      [11C]colchicine, [11C]verapamil and [11C]daunorubicin, have been evaluated for
      the quantification of Pgp-mediated transport with PET in vivo. The results
      suggest that radiolabelled colchicine, verapamil and daunorubicin are feasible
      substrates with which to image Pgp function in tumours. Uptake of [11C]colchicine
      and [11C]verapamil is relatively high in the chest area, reducing the value of
      both tracers for monitoring Pgp-mediated drug transport in tumours located in
      this region. In addition, it has to be borne in mind that only comparison of Pgp
      mediated transport of radioalabelled substrates in the absence and in the
      presence of Pgp blockade gives quantitative information on Pgp-mediated
      pharmacokinetics. Leukotrienes are specific substrates for MRP. Therefore, N
      [11C]acetyl-leukotriene E4 provides an opportunity to study MRP function non
      invasively. Results obtained in MRP2 mutated GY/TR rats have demonstrated
      visualization of MRP-mediated transport. This tracer permits the study of MRP
      transport function abnormalities in vivo, e.g. in Dubin-Johnson patients, who are
      MRP2 gene deficient. Results obtained show the feasibility of using SPET and PET
      to study the functionality of MDR transporters in vivo.

PMID- 10079322
TI  - Gender differences in gastric emptying.

PMID- 10079323
TI  - The PNM2 mutation in the prion protein domain of SUP35 has distinct effects on
      different variants of the [PSI+] prion in yeast.
AB  - We have previously described different variants of the yeast prion [PSI+] that
      can be obtained and maintained in the same genetic background. These [PSI+]
      variants, which differ in the efficiency of nonsense suppression, mitotic
      stability and the efficiency of curing by GuHCl, may correspond to different
      [PSI+] prion conformations of Sup35p or to different types of prion aggregates.
      Here we investigate the effects of overexpressing a mutant allele of SUP35 and
      find different effects on weak and strong [PSI+] variants: the suppressor
      phenotype of weak [PSI+] factors is increased, whereas the suppressor effect of
      strong [PSI+] factors is reduced. The SUP35 mutation used was originally
      described as a "Psi no more" mutation (PNM2) because it caused loss of [PSI+].
      However, none of the [PSI+] variants in the strains used in our study were cured
      by PNM2. Indeed, when overexpressed, PNM2 induced the de novo appearance of both
      weak and strong [PSI+] variants with approximately the same efficiency as the
      overexpressed wild-type SUP35 allele. Our data suggest that the change in the
      region of oligopeptide repeats in the Sup35p N-terminus due to the PNM2 mutation
      modifies, but does not impair, the function of the prion domain of Sup35p.

PMID- 10079324
TI  - RPD3 (REC3) mutations affect mitotic recombination in Saccharomyces cerevisiae.
AB  - Prior research identified the recessive rec3-1ts mutation in Saccharomyces
      cerevisiae which, in homozygous diploid cells, confers a conditional phenotype
      resulting in reduced levels of spontaneous mitotic recombination and loss of
      sporulation at the restrictive temperature of 36 degrees C. We found that a 3.4
      kb genomic fragment that complements the rec3-1ts/rec3-1ts mutation and which
      maps to chromosome XIV, is identical to RPD3, a gene encoding a histone de
      acetylase. Sporulation is reduced in homozygous diploid strains containing the
      rec3-1ts allele at 24 degrees C, suggesting that this allele of RPD3 encodes a
      gene product with a reduced function. Sporulation is abolished in diploid strains
      homozygous for the rpd3Delta or rec3-1ts alleles, as well as in rpd3Delta/rec3
      1ts heteroallelic diploids, at the non-permissive temperature. Acid-phosphatase
      expression has been shown to be RPD3 dependent. We found that acid-phosphatase
      activity is greater in diploid strains homozygous for the temperature-sensitive
      rec3-1ts allele than in RPD3/RPD3 strains and increased further when mutant
      strains are grown at 36 degrees C. We also tested the rpd3Delta/rpd3Delta strains
      for their effects on spontaneous mitotic recombination. By assaying a variety of
      intra- and inter-genic recombination events distributed over three chromosomes,
      we found that in the majority of cases spontaneous mitotic recombination was
      reduced in diploid rpd3Delta/rpd3Delta cells (relative to a RPD3/RPD3 control).
      Finally, although 90% of mitotic recombinant events are initiated in the G1 phase
      of the growth cycle (i.e., before DNA synthesis) we show that RPD3 is not
      regulated in a cell-cycle-dependent manner. These data suggest that mitotic
      recombination, in addition to gene expression, is affected by changes in
      chromatin architecture mediated by RPD3.

PMID- 10079325
TI  - Starvation in yeast increases non-adaptive mutation.
AB  - The frequency of reversion in a histidine-requiring mutant of Saccharomyces
      cerevisiae increases about ten-fold in stationary cells during histidine
      starvation. Histidine starvation enhances a similar frequency of reversion in a
      tryptophan-requiring mutant. Starvation, therefore, enhances mutation frequencies
      in a non-adaptive manner. The base analogue 6-N-hydroxylaminopurine (HAP) added
      prior to plating on medium with limited histidine strongly increases reversion of
      the histidine mutant. HAP-induced reversion increases further in stationary
      starving cells with the same kinetics as that which increases spontaneous
      reversion. Adding HAP to the stationary starving cells does not produce any
      effect.

PMID- 10079326
TI  - Transient inhibition of histone deacetylase activity overcomes silencing in the
      mating-type region in fission yeast.
AB  - We have investigated the effects of inhibition of histone de-acetylase activity
      on silencing at the silent mating-type loci in fission yeast. Treatment of
      exponentially growing cells with the histone deacetylase inhibitor, trichostatin
      A (TSA), resulted in derepression of a marker gene inserted 150 bp distal from
      the silent mat3-M locus. The natural targets for the silencing mechanism in this
      region were only partially derepressed and the activation appeared to be
      asymmetric, i.e. the mat2-P cassette remained silent at concentrations that
      clearly partially derepressed the mat3-M cassette. We further noted that
      treatment of wild-type h90 cells resulted in the generation of altered
      sporulation phenotypes, indicating that the treatment affected the expression of
      mating-type genes and/or mating-type switching. The results are discussed in the
      light of recent accumulated data regarding the role of deacetylation for
      silencing in other species.

PMID- 10079327
TI  - Systematic mutagenesis of the fission yeast Srp54 protein.
AB  - The signal recognition particle (SRP) is a ribonucleoprotein required for
      targeting a subset of nascent pre-secretory proteins to the endoplasmic reticulum
      membrane. Of the six SRP polypeptides, the most highly conserved is Srp54p, a
      modular protein consisting of an amino-terminal (N) domain of unknown function, a
      central GTPase (G) domain, and a carboxyl-terminal (M) domain implicated in the
      recognition of both signal sequences and SRP RNA. To identify regions of Srp54p
      that interact with other SRP subunits or regulatory proteins, we carried out
      systematic mutagenesis of the fission yeast homolog, principally using a
      "clustered charged-to-alanine" strategy. Of the 35 alleles examined, 13 are
      unable to support growth, two confer cold-sensitivity, five confer heat
      sensitivity, and 15 produce no discernible phenotype. The lethal and conditional
      mutations map throughout the protein to several conserved regions, confirming
      that these motifs play critical roles in Srp54p function. The effects of the
      amino-acid substitutions are analyzed with reference to the recently determined
      tertiary structures of the N/G domain and the intact protein from a thermophilic
      bacterium.

PMID- 10079328
TI  - Mitochondrial copper metabolism in yeast: mutational analysis of Sco1p involved
      in the biogenesis of cytochrome c oxidase.
AB  - Saccharomyces cerevisiae Sco1p is believed to be involved in the transfer of
      copper from the carrier Cox17p to the mitochondrial cytochrome c oxidase subunits
      1 and 2. We here report on the results of a mutational analysis of Sco1p. The two
      cysteine residues of a potential metal-binding motif (CxxxC) are essential for
      protein function as shown by their substitution by alanines. Chimeras consisting
      of Sco1p and its homolog S. cerevisiae Sco2p restrict the specificity of Sco1p
      function to the N-terminal half of the protein. A candidate region for conferring
      specificity on Sco1p is a stretch of hydrophobic amino acids, which act as a
      membrane anchor. In line with this suggestion is the result that alterations of
      individual amino acids within this region impair Sco1p function.

PMID- 10079329
TI  - A long open reading frame in the mitochondrial LSU rRNA group-I intron of
      Cryphonectria parasitica encodes a putative S5 ribosomal protein fused to a
      maturase.
AB  - A 4238-bp intervening sequence within the highly conserved U11 region of the
      mitochondrial large subunit ribosomal RNA gene of the fungus Cryphonectria
      parasitica Ep155 has been sequenced and identified to be a group-I intron. This
      is the largest group-I intron reported to-date for fungal mitochondrial genomes.
      The intron contains an 851-codon open reading frame encoding a putative, but
      complete, small-subunit ribosomal protein of 510 amino acids which is fused at
      its carboxyl terminus to a 311 amino-acid polypeptide representing a typical
      maturase-like protein. A short open reading frame of 83 amino acids with some
      similarity to maturases, but lacking a translation-initiation codon, was also
      noted at the 3' end of the intron. The unusual size of the intron and the
      arrangement of the open and truncated reading frames suggest that this segment of
      the mtDNA of C. parasitica has arisen by a fusion of components from two or more
      different introns, possibly involving the re-location of intronic genes.

PMID- 10079330
TI  - Cloning, characterisation and regulation of the ornithine transaminase (otaA)
      gene of Aspergillus nidulans.
AB  - The ornithine transaminase (otaA) gene of Aspergillus nidulans has been cloned by
      transformation of the A. nidulans pro-ota- mutant strain with a cosmid gene
      library. The otaA gene contains two introns and potentially codes for a 453-aa
      long protein. The deduced amino-acid sequence is homologous to known ornithine
      transaminases from Saccharomyces cerevisiae, Plasmodium falciparum, Vigna
      aconitifolia, rat, mouse and man, particularly in the pyridoxal phosphate-binding
      domain. The expression of the otaA gene is specifically induced by arginine, and
      is also under the control of nitrogen-metabolite and carbon-catabolite
      repression. Regulation of the gene occurs at both transcriptional and post
      transcriptional levels. The promoter region of otaA contains putative AREA and
      CREA binding-sites. Fusion proteins containing AREA or CREA DNA-binding domains
      bind some of these sites. CREA binding-sites correspond very well to the CREA
      binding consensus sequence which is SYGGRG. AREA binding-sites are composed of
      GATT sequences which are not typical binding sites for the GATA - binding family
      of transcription factors.

PMID- 10079331
TI  - Mating system of the filamentous ascomycete, Glomerella cingulata.
AB  - Mating in heterothallic filamentous ascomycetes is typically controlled by a
      single mating-type locus with two alternate alleles or idiomorphs. In this study,
      five self-sterile strains of Glomerella cingulata from pecan were crossed in all
      possible combinations. Four of the five strains could be placed into two mating
      type groups, but the fifth strain was sexually compatible with all of the other
      strains. Single ascospore progeny were isolated from each of the successful
      crosses, tested for self-fertility, and backcrossed with both parents. In
      addition, subsets of F1 isolates were crossed with all five of the original
      strains from pecan and in all possible combinations with each other. Results from
      the crosses showed that the ascospore progeny had stably inherited the mating
      pattern of one of the parental strains and that the mating type had segregated
      1:1 among the F1 isolates. Furthermore, the five strains from pecan were sexually
      compatible with five additional heterothallic strains in all but one combination.
      Data from these experiments are consistent with a mating system composed of a
      single mating-type locus with multiple alternate alleles. We believe that this is
      the first report of this type of mating system for an ascomycete species.

PMID- 10079332
TI  - A new family of Pneumocystis carinii genes related to those encoding the major
      surface glycoprotein.
AB  - A new family of Pneumocystis carinii genes (called MSR for MSG-related) that
      encodes peptides related to the major surface glycoprotein (MSG) is described.
      Members of the MSR sequence family are linked to MSG genes and are located near
      the ends of at least 13 chromosomes. Transcripts encoding different MSR isoforms
      were present in a single population of P. carinii f. sp. carinii, showing that
      multiple MSR genes were expressed. Two size classes of MSR mRNA, 2.4 and 3.5 kb,
      were detected. Both sizes of MSR mRNA lacked the upstream conserved sequence
      (UCS), which is found on the 5' end of MSG mRNAs because MSG genes must be linked
      to the UCS to be transcribed. The absence of the UCS from MSR mRNAs suggests that
      expression of MSR genes does not require linkage to the UCS locus.

PMID- 10079333
TI  - The tamA mutants of Aspergillus nidulans.

PMID- 10079334
TI  - Further experience with ECMO.

PMID- 10079335
TI  - Comparison of venoarterial versus venovenous access in the cerebral circulation
      of newborns undergoing extracorporeal membrane oxygenation.
AB  - This study was designed to compare venoarterial (VA) with venovenous (VV) access
      in the cerebral circulation of newborn infants during extracorporeal membrane
      oxygenation (ECMO). Among 14 infants with VA ECMO, 7 had no intracranial
      complications (group 1), while the others (group 2) developed intracranial
      hemorrhage (ICH). In contrast, among 19 infants with VV ECMO, only 1 developed
      ICH. Serial echocardiograms were performed before and after 1, 6, 12, and 24 h
      and 2 and 3 days of ECMO. The mean cerebral blood flow (CBF) velocities were
      measured in the anterior cerebral artery (ACA), right and left internal carotid
      arteries (Rt, Lt-ICA), basilar artery (BA), and right and left middle cerebral
      arteries (Rt, Lt-MCA). Ejection fraction (EF), cardiac output (CO), and stroke
      volume (SV) were also measured using standard echography. The velocity levels in
      the ACA, Rt-MCA, and Lt-MCA in VA ECMO were lower than those in VV ECMO, while
      those in the Lt-ICA and BA in VA ECMO were higher than those in VV ECMO. The EF,
      CO, and SV were lower in cases of VA ECMO than in VV ECMO. In cases of VA ECMO,
      there were no differences between groups 1 and 2 in velocities in the ACA, Rt
      ICA, or Lt-ICA. However the velocities in group 2 in the BA, Rt-MCA, and Lt-MCA
      were lower than those in group 1 before and during ECMO. Similarly, the EF, CO,
      and SV were lower in group 2 (12.0%-31.0%, 0. 10-0.32 l/min, and 0.66-1.55 ml,
      respectively) than in group 1 (29. 5%-49.3%, 0.25-0.63 l/min, and 2.15-3.85 ml)
      during ECMO. However, in the infants on VV ECMO the CBF was either maintained or
      gradually increased before and during ECMO. Their cardiac parameters were: EF
      46.1%-53.0%, CO 0.43-0.52 l/min, and SV 2.72-3.84 ml during ECMO. It is concluded
      that in VA ECMO CBF velocities, particularly in infants who developed ICH,
      decreased after the onset of ECMO in association with poor cardiac function,
      while in VV ECMO they were stable, probably due to normal systemic hemodynamics
      and cardiac function.

PMID- 10079336
TI  - Paraoesophageal hernia in children: familial occurrence and review of the
      literature.
AB  - Paraoesophageal hernia (PH) in children is a rare entity, and most reported cases
      refer to adult patients. Its etiology is not precisely known, but the hypothesis
      of its congenital origin is widely accepted. Similarly to other congenital
      diaphragmatic defects, PH follows a sporadic pattern of incidence in most cases.
      Familial occurrence of sliding hiatal herniae has been reported in more than 20
      cases, but only one family with two members affected by PH was described in the
      literature. We present two pairs of siblings with the paraoesophageal type of
      hiatus hernia and discuss the clinical presentation of this anomaly in children.

PMID- 10079337
TI  - Gastric outlet obstruction due to corrosive ingestion: incidence and outcome.
AB  - A retrospective clinical study was performed to determine the incidence,
      management, and outcome of gastric outlet obstruction (GOO) caused by caustic
      ingestion in children. Of 220 patients who sustained caustic substance ingestion
      and were treated at our unit between 1976 and 1996, 168 ingested alkaline
      substances; of these, 9 children (5.3%) developed GOO in addition to esophageal
      strictures. The remaining 52 patients ingested acid agents, and 2 of them (3.8%)
      presented with GOO without esophageal strictures. The overall incidence of
      corrosive GOO was 5% (n = 11). The mean age of the patients with GOO was 5.7 +/-
      2.8 years (range 2-14) with a female:male ratio of 6:5. Sodium hydroxide (n = 6),
      potassium hydroxide (n = 3), and hydrochloric acid (n = 2) were the ingested
      caustic agents. The patients were subdivided into two groups according to serial
      endoscopic and radiologic findings: group I: moderate (dense superficial and
      spotty ulcerations with intact mucosa) mucosal injury with partial pyloric
      obstruction; and group II: severe (deep ulcerations, extreme hemorrhagic
      erosions, eschar formation with white plaques) mucosal injury with complete
      pyloric obstruction. Group I consisted of 5 patients who ingested alkali agents
      while group II included 6 who presented with ingestion of alkaline (n = 4) and
      acid (n = 2) agents. Surgical treatment included Billroth I (n = 6) operations
      performed in group II and Finney (n = 3) and Heineke-Mikulicz (n = 2)
      pyloroplasty procedures done in group I. All patients are alive without any
      complaints. Fiberoptic endoscopy should be the preferred method of evaluating a
      patient with ingestion of a corrosive agent. It determines the presence of injury
      and assesses the extent of damage, establishing the diagnosis and allowing
      therapy to be instituted immediately. Our experience revealed that substantial
      damage has occurred early after ingestion, and early surgical intervention has
      decreased the morbidity and mortality. The extent of the mucosal injury and
      status of the pylorus and antrum determined the type of surgical treatment. A
      Billroth I procedure recommended for severely injured mucosa with complete
      pyloric obstruction, and pyloroplasty for moderate mucosal injury associated with
      partially obstructed but still viable pylorus. In contrast to the current belief,
      alkali ingestion also has a high risk of corrosive gastric injury causing GOO,
      which should be considered during assessment of the injury. We emphasize that a
      detailed evaluation of radiologic and especially endoscopic findings is very
      important for determining the timing, necessity, and type of appropriate surgical
      treatment.

PMID- 10079338
TI  - Distal splenorenal shunt with splenopancreatic disconnection for portal
      hypertension in biliary atresia.
AB  - This study evaluated the long-term effects of distal splenorenal shunt with
      splenopancreatic disconnection (DSRS-SPD) on portal hypertension (PH) in biliary
      atresia (BA) patients. Five patients with BA underwent DSRS-SPD at the age of 3.3
      to 8.5 years. They had been free from jaundice after hepatic portoenterostomy
      (HPE); however, they gradually developed gastroesophageal varices and
      hypersplenism. Portal venous pressure after anastomosis was 37.2 +/- 6.1 cmH2O,
      as high as that before anastomosis (37.8 +/- 3.3 cmH2O). Postoperatively, liver
      function tests became worse within 2 weeks; however, they returned to
      preoperative levels within 1 month without any further treatment. No patient
      developed a significant encephalopathy throughout the observed period. During
      follow-up of 4 to 12 years, the shunt was patent in all patients. Spleen size
      decreased after operation. Abdominal-wall venous dilatation completely
      disappeared in two of four patients. The platelet counts gradually increased and
      were significantly higher 3 years (126.6 +/- 59.3 x 10(3)/mm3) after DSRS-SPD
      than preoperative values (66.0 +/- 24.2 x 10(3)/mm3). White blood cell counts
      showed no significant changes. No patient developed a gastrointestinal hemorrhage
      postoperatively, although three had had repeated hemorrhages before the
      operation. Two patients showed disappearance of varices endoscopically at 2 years
      and 7 months after DSRS-SPD, respectively, but had recurrent varices at 7 and 11
      years, respectively. The endoscopic findings regarding varices 3 to 7 years after
      DSRS-SPD were as follows: decreased number (80%); decreased length (40%);
      improvement of form (20%); improvement of fundamental color (60%); disappearance
      of red-color sign (100%); disappearance of gastric varices (75%); and
      disappearance of acute gastric mucosal lesions (100%). Although one patient later
      underwent liver transplantation because of progression of liver cirrhosis, all
      five are doing well. From these results, DSRS-SPD may prove to be a safe and
      feasible procedure for intrahepatic PH after HPE for BA and may improve
      gastroesophageal varices and hypersplenism on long-term follow-up.

PMID- 10079339
TI  - Pre-term and particularly pre-labor cesarean section to avoid complications of
      gastroschisis.
AB  - The marked advantages and merit of pre-term and particularly pre-labor (PTPL)
      cesarean section (C-section) in the avoidance, and indeed, virtual elimination of
      severely disabling gastroschisis (GS) complications in infants diagnosed prior to
      birth by ultrasound has unfortunately remained controversial in the 10 to 12
      years since it was first reported and strongly recommended by numerous authors.
      During this period, GS has remained one of the four major causes of the short-gut
      syndrome (SGS) in infancy and childhood and a major cause of prolonged, costly,
      complicated, and hazardous neonatal intensive care unit stays with requirements
      for total parenteral nutrition (TPN). The most serious and frequent complications
      of GS in infants born without PTPL C-section are the occurrence of the "peel",
      which greatly enlarges and rigidifies the eviscerated gut, and of "complicated
      GS" (intestinal atresia/s, stenosis, necrosis, perforations) (CGS). The "peel"
      occurs in 100% of these cases and CGS in approximately 20%. "Peel" enlargement
      and rigidification of eviscerated intestine in the presence of a reduced
      peritoneal cavity causes great difficulty in covering the eviscerated, enlarged,
      and rigidified gut with abdominal wall, skin, a prosthesis, etc., and frequently
      produces gut ischemia from excessive pressure, which may lead to necrotizing
      enterocolitis (NEC) and SGS as well as prolonged hospital stays. The presence of
      a "peel" greatly complicates the hazards of dealing with cases of CGS, as
      resection and anastomosis are virtually impossible in the presence of a "peel."
      The authors report personal experience with 77 cases of GS dating as far back as
      1951; 44 of the infants were born after the onset of labor by vaginal or C
      section delivery and all had some degree of "peel" formation. Of 320 cases from
      the literature (including some of the cases reported here), 61 (19.1%) involved
      CGS. Of the 33 cases born PT, and especially PL, there were no cases of "peel"
      and only 1 case of CGS (3.0%). This infant had a single atresia associated with a
      very small (1 cm) defect in the abdominal wall and no labor-induced "peel," which
      was easily and successfully repaired by resection and anastomosis. The 6.4-fold
      reduction in the occurrence of CGS by PTPL C-section (3.0% vs 19.1%) was
      statistically significant by the chi-square test (P < 0.05), as was the 100%
      elimination of the disabling "peel." If the single case of CGS associated with a
      very small defect and no labor or labor-associated "peel" is eliminated, the
      incidence of CGS in the remaining PTPL group of 32 cases falls to 0 (0% versus
      19.1%, P < 0.007). PT and especially PL C-section may be expected to virtually
      eliminate "peel" formation and CGS and to remove GS as one of the four major
      causes of SGS. The findings of this report that PT labor prior to PT C-section
      may result in both "peel" formation and CGS further solidifies the role of labor
      in the production of both the "peel" and the equally disabling CGS. Failure to
      appreciate the central role of labor in GS complications has doubtless
      contributed to the persistent controversy concerning the value and importance of
      PTPL C-section for gastroschisis diagnosed in utero. The pediatric surgeon has an
      important responsibility with the obstetrician to monitor the possible occurrence
      of occult labor in the waning weeks of pregnancy and be prepared to do a prompt C
      section if it occurs and there is adequate lung maturity. The achievement of
      "peel"- and CGS-free gut would greatly facilitate the use of the new Bianchi
      technique of gut reduction without anesthesia. The combination of the use of
      epidural anesthesia for the elective PTPL C-section with the Bianchi approach
      would spare both mother and baby any untoward effects of general anesthesia and
      present the potential for massive reductions in hospital costs with minimal
      patient manipulation and disturbance. For infants born with labor-associated
      "peel," re-evaluation of the suitability and effectiv

PMID- 10079340
TI  - Is barium enema reduction safe and effective in patients with a long duration of
      intussusception?
AB  - The aim of this study was to determine whether barium enema reduction (BER) is
      safe and effective in patients with a long duration of intussusception. Over the
      last 17 years, 104 patients were admitted to our hospital with a diagnosis of
      intussusception. All except 1 with peritonitis underwent BER primarily. Of the
      103 intussusceptions treated primarily by BER, 84 (82%) were reduced by the enema
      alone, whereas 19 (18%) underwent surgical reduction. There were no differences
      in mean duration of disease between the patients with successful and failed enema
      reduction (successful: 15 +/- 14 h; failures: 14 +/- 11 h, P = 0.6). The success
      rate of BER was 85% within 12 h of symptoms, 76% for 12-24 h, and 71% for more
      than 24 h. Of 8 cases with a second trial, 4 (50%) were reduced by repeated
      barium enema. There were no deaths and no intestinal perforations. The success
      rate of more than 70% even in patients with a long duration of intussusception
      suggests that BER is safe and effective regardless of the duration of the
      disease.

PMID- 10079341
TI  - Posterior sagittal transanorectal approach in patients with ambiguous genitalia:
      report of eight cases.
AB  - The posterior sagittal transanorectal approach was used for reconstruction of the
      female genitalia (vaginoplasty) in eight girls with urogenital sinus, high
      vaginal implantation, and normal rectum, in all cases with a protective
      sigmoidostomy. These eight patients included four female and four male
      pseudohermaphrodites. They remain fecally continent, but only seven have urinary
      continence. One girl has a neuropathic bladder: umbilical discomfort during
      abdominal straining is present in one patient. One girl married and demonstrated
      satisfactory sexual intercourse. All patients are alive and healthy, physically
      and mentally. The transanorectal approach allows separation of the vagina from
      the urethra and bladder, provides good vaginal mobilization down to the perineum,
      avoids the utilization of perineal skin flaps and sometimes a laparotomy, and
      preserves defecation and urinary control. The cosmetic appearance of the
      genitalia seems to be better than that achieved in the past with other
      techniques.

PMID- 10079342
TI  - Management of rectal prolapse in children: Ekehorn's rectosacropexy.
AB  - Although surgical intervention is occasionally required for rectal prolapse (RP),
      there is both vagueness as to the indications for surgery and confusion as to the
      technique that should be used for children who need surgical treatment. Using
      Ekehorn's transanal suture rectosacropexy technique, 56 children with RP were
      treated surgically between 1987 and 1998 at our hospital. There were 36 boys and
      20 girls, the average age was 4.5 years, and the duration of the recurrent
      prolapse prior to admission ranged from 3 to 8 months. The technique consists of
      simply inserting one "U"-shaped suture through the rectal ampulla and tying the
      strands of the suture outside at the level of the sacrococcygeal junction. In
      this series, follow-up periods ranged from 1 to 10 years and there were no
      recurrences. We believe that surgical indications for RP need to be defined more
      clearly and that Ekehorn's technique offers a simple and effective method for the
      surgical treatment of complete RP in children.

PMID- 10079343
TI  - The infantile inguinal hernia - a bilateral disease?
AB  - Controversy continues whether exploration of the contralateral, asymptomatic side
      should routinely be performed since Rothenberg and Barnett stated in 1955 that a
      contralateral hernia is present in three out of four children presenting with a
      symptomatic unilateral inguinal hernia (IH). In our institution, hernia
      operations are performed on the symptomatic side only, the exception being male
      infants under 1 year of age with a left-sided IH. To verify our concept and to
      evaluate the frequency of contralateral hernial development, the medical records
      of all infants under 1 year of age operated upon between 1984 and 1988 were
      reviewed and the children followed through December 1996. Included in the study
      were 882 infants, 616 boys (70%) and 266 girls (30%); 148 (17%) were born
      prematurely. Seventy percent were operated upon before the end of the 3rd month
      of life. In 761 infants clinical signs of a unilateral hernia were present, and
      in 121 symptomatic hernias were found on both sides; 665 infants were operated
      upon unilaterally. A second operation on the opposite side was necessary in 38
      cases (5.7%). The highest incidence of contralateral hernial development was
      found in premature boys (11.5%). We conclude that even in infants below 1 year of
      age, IH is usually a unilateral disease and does not require routine exploration
      of the asymptomatic side.

PMID- 10079344
TI  - Analysis of meatal location in 1,244 healthy men. Definition of the normal site
      justifies the need for meatal advancement in pediatric anterior hypospadias
      cases.
AB  - The normal site of the external urethral meatus on the glans penis and the need
      for meatal advancement in patients with anterior hypospadias was studied. The
      location of the external meatus was analyzed in 1,244 men (mean age 28 years)
      with classification of the meatal position in relation to the tip of the glans
      and corona. The quality of erections and sexual intercourse, the presence of a
      penile curvature, urinary stream, and ability to void in a standing position were
      assessed in an interview. In 1,198 men (96.3%) the meatus was located on the
      distal third of the glans, in 43 (3.5%) on the middle third, (B), and in 3 (0.2%)
      on the posterior third. In no case was it located below the corona. One of the 3
      men with the meatus on the posterior third had an associated mild penile
      curvature that did not cause difficulty in sexual intercourse. This study
      suggests that the normal site of the external meatus is at the tip of the glans.
      The definition of the normal site and the percentage of men with a normal meatal
      position justifies the need for meatal advancement in patients with anterior
      hypospadias when the goals of current hypospadias surgery are considered.

PMID- 10079345
TI  - A conservative treatment for ingrown toenails in children.
AB  - Ingrowing nails are not uncommon in children, and even so receive little
      attention in the pediatric surgery literature. The purpose of the present study
      was to demonstrate our modification of the conservative treatment of ingrowing
      nails. Our technique of local treatment combined with patient education for
      better foot and toe care was successfully used and well tolerated by 19 out of 20
      young patients with ingrown toenails.

PMID- 10079346
TI  - Fibrosarcoma in infants and children: a retrospective analysis - overdiagnosis in
      earlier years.
AB  - During a 30-year period, 22 patients considered to have a fibrosarcoma (FS) were
      treated. In a retrospective study the clinicopathologic findings were summarized.
      With histologic and immunohistochemical re-evaluation, the diagnosis was
      confirmed in 8 cases. For 6 further patients FS was very probable but specimens
      were not available. In 8 cases the diagnosis was revised and benign lesions were
      found in 7. Two patients with irresectable tumors died (infantile FS, FS of
      mesentery and retroperitoneum). After repeated local recurrences and spread on
      the affected extremity, an amputation was life-saving in 1 boy. In earlier years
      many tumors were classified as FSs. Today, immunohistochemistry and molecular
      biological methods are valuable tools to clearly identify these tumors. Wide
      local excision or en-bloc resection without sacrificing any significant function
      of the part should be the primary form of treatment in infants. Primary re
      excision after incomplete excision should have priority over any adjuvant
      treatment. Preoperative chemotherapy may avoid incomplete resection or mutilation
      in cases with extended congenital FS.

PMID- 10079347
TI  - Granuloma inguinale (donovanosis) presenting as a neck mass in an infant.
AB  - A case of granuloma inguinale (GI) presenting as a lateral neck mass in a 4-month
      old, HIV-positive infant is described. The histological features of the mass were
      typical of GI, with numerous macrophages containing intracellular organisms with
      a "closed-safety-pin" appearance. This is a rare occurrence, and the mode of
      transmission of infection is discussed. An awareness of GI in infants by both
      clinicians and pathologists is important to prevent morbidity and allow for
      prompt institution of appropriate treatment.

PMID- 10079348
TI  - Gastrojejunal interposition for esophageal replacement.
AB  - The main considerations in replacing the esophagus are to avoid postoperative
      necrosis of all or part of the graft, leakage or stenosis of the anastomoses, and
      complications related to acid-peptic or alkaline reflux. A 5-year-old boy, after
      two unsuccessful thoracic operations for atresia and then stenosis of the
      esophagus, underwent resection of the esophagus because of duodeno
      gastroesophageal reflux. The continuity of the alimentary tract was restored by
      gastrojejunal interposition. We recommend this method of reconstruction when the
      esophago-gastrostoma is created in the chest, and the possibility of alkaline
      reflux must be considered.

PMID- 10079349
TI  - Total gastric replacement following gas bloat in a 21-month-old child.
AB  - A 21-month-old child with a previously repaired left congenital diaphragmatic
      hernia underwent a 360 degrees 'loose-wrap' Nissen fundoplication for
      gastroesophageal reflux. Failure to replace the dislodged nasogastric tube on the
      2nd night led to severe gas bloat and total gastric infarction. A 30-cm
      retrocolic, N-shaped, isoperistaltic jejunal pouch was constructed for gastric
      replacement. A pyloromyotomy ensured free emptying and a pouchostomy secured the
      pouch to the abdominal wall. At 8 months all nutrition was oral except for a
      biannual vitamin B12 injection, there was no dumping, and the pouchostomy was
      removed. By 18 months growth, originally along the 10th centile, was sustained at
      the 50th centile. Our early impression recommends a 30-cm retrocolic,
      isoperistaltic, N-shaped jejunal pouch similar to that of Hays and Clark as a
      safe and effective replacement for the stomach in children.

PMID- 10079350
TI  - Extrahepatic biliary atresia associated with trisomy 18.
AB  - A case of extrahepatic biliary atresia (EBA) associated with trisomy 18 is
      presented. A 1-month-old boy was suspected to have Alagille syndrome with
      obstructive jaundice, a systolic heart murmur, growth retardation, and a small,
      pointed chin. However, surgery and chromosomal analysis revealed EBA associated
      with trisomy 18. Chromosomal examination must be performed in patients with
      jaundice and congenital anomalies. It is possible that EBA in trisomy 18 syndrome
      is due to a chromosomal disorder.

PMID- 10079351
TI  - Spontaneous splenic rupture in infectious mononucleosis: conservative management
      with gradual percutaneous drainage of a subcapsular hematoma.
AB  - Spontaneous splenic rupture (SSR) is a rare but potentially lethal complication
      of infectious mononucleosis (IM). Because the inflamed spleen is usually
      enlarged, congested, and friable, emergency splenectomy is recommended. We
      describe the conservative management of a SSR in a 16-year-old boy with IM. A
      pigtail catheter was inserted under ultrasonographic guidance and left in place
      for 36 h. This allowed the successful evacuation of the hematoma without
      compromising the splenic parenchyma.

PMID- 10079352
TI  - A male newborn with colonic atresia and total colonic aganglionosis.
AB  - A case of colonic atresia (CA) and aganglionosis is presented, which is probably
      the tenth in the English literature. The boy presented on day 3 of life with
      delayed passage of meconium, milk intolerance, and progressive abdominal
      distension. A barium enema study was complicated by barium peritonitis. Emergency
      peritoneal lavage was done and the intestinal obstruction was relieved by a
      proximal defunctioning ileostomy; type III CA (Grosfeld classification) was
      identified. The proximal atretic end was the blind-ending caecum and the distal
      atretic end commenced in the splenic area as a microcolon extending to the pelvis
      and replacing the normal colon. Total colonic aganglionosis (TCA) was confirmed
      by biopsies. This is the first case in the literature of TCA with CA documented
      before any attempts at colonic resection and anastomosis were made. This
      association highlights the recommendation for biopsy of the micro-colon and
      rectum when Type III CA (Grosfeld classification) is encountered in a newborn.
      The infant underwent a cholecystectomy and Duhamel-Martin operation at 14 months
      that was complicated by abdominal wound dehiscence; the ileostomy was closed at
      22 months of age.

PMID- 10079353
TI  - Wet umbilicus caused by pancreatic heterotopia in urachal remains.
AB  - Drainage from the umbilicus may be due to the presence of structures derived from
      the vitelline duct or urachus, granulomas, ectopic tissue, or poor hygienic
      practice. This paper discusses the case of a 6-month-old infant with a wet
      umbilicus caused by ectopic pancreatic tissue, in urachal remains. No similar
      cases have been found in the literature.

PMID- 10079354
TI  - Torted ovarian cyst with lethal bleeding diathesis in an infant.
AB  - We report a 9-month-old infant with a torted ovarian cyst who presented with an
      acute consumptive coagulopathy (CC) with lethal outcome. That ischemic tissue can
      act as a trigger for a CC is well-known, but we did not find any report of a
      torted ovarian cyst causing a coagulopathy in the pediatric literature. This
      potential complication constitutes one more reason for the prompt surgical
      removal of torted ovarian cysts in infants.

PMID- 10079355
TI  - Lipoma of the preputium clitoridis in neonate: an exceptional abnormality
      different from ambiguous genitalia.
AB  - A lipoma of the preputium clitoridis was found in a newborn girl. Ambiguous
      genitalia was first suspected. Surgery was successfully performed at 5 months.

PMID- 10079356
TI  - Region-specific cell clones in the developing spinal cord of the zebrafish.
AB  - To analyse the proliferative abilities of cells within particular regions of the
      zebrafish neural plate, injections of fluorescein-dextran were made into single
      cells at either medial or intermediary positions in the neural plate region of
      two-somite stage embryos. The resulting cell clones were analysed in 3. 5-day-old
      embryos. Clones with similar compositions were found among those derived from
      injections in both regions, and these were grouped into classes. 78 clones 29
      obtained following injections in the medial region, and 22 of 59 cell clones
      derived from injections in the intermediary region, were classifiable into 9 and
      10 different classes, respectively, each comprising a variable number of clones.
      Several identified cell types, as well as each of the clone classes themselves,
      were specific for the regions of the neural plate from which they derived, i.e.
      they were not represented among the clones derived from the other region. These
      results suggest that the composition of the lineages derived from particular
      cells is constant in different animals.

PMID- 10079357
TI  - Segmentation gene expression in the mothmidge Clogmia albipunctata (Diptera,
      psychodidae) and other primitive dipterans.
AB  - To obtain a clearer understanding of the evolutionary transition between short-
      and long-germ modes of embryogenesis in insects, we studied the expression of two
      gap genes hunchback (hb) and Kruppel (Kr) as well as the pair-rule gene even
      skipped (eve) in the dipteran Clogmia albipunctata (Nematocera, Psychodidae).
      This species has features of both short- and long-germ mode of embryogenesis. In
      Clogmia hb expression deviates from that known in Drosophila in two main
      respects: (1) it shows an extended dorsal domain that is linked to the large
      serosa anlage, and (2) it shows a terminal expression in the proctodeal region.
      These expression patterns are reminiscent of the hb expression pattern in the
      beetle Tribolium, which has a short germ mode of embryogenesis. Kruppel
      expression, on the other hand, was found to be rather similar to the Drosophila
      expression, both at early and late stages. eve expression starts with six stripes
      formed at blastoderm stage, while the seventh is only formed after the onset of
      gastrulation and germband extension. Surprisingly, no segmental secondary Eve
      stripes could be observed in Clogmia although such segmental stripes are known
      from higher dipterans, beetles and hymenopterans. We therefore also studied
      another nematoceran, Coboldia, to address this question and found that some
      segmental stripes form by intercalation as in Drosophila, although belatedly. Our
      results suggest that Clogmia embryogenesis, both with respect to morphological
      and molecular characteristics represents an intermediate between the long-germ
      mode known from higher dipterans such as Drosophila, and the short-germ mode
      found in more ancestral insects.

PMID- 10079358
TI  - Rapid divergence in the course of Drosophila evolution reveals structural
      important domains of the Notch antagonist Hairless.
AB  - Hairless is a member of the Notch signalling pathway, where it acts as antagonist
      by binding to Suppressor of Hairless [Su(H)], thereby inhibiting Notch target
      gene activation. The pathway and its members are highly conserved in metazoans
      from worms to humans. However, a Hairless orthologue from another species has not
      yet been identified. The identification of Hairless in largely diverged species
      by cross-hybridization has failed so far probably due to a low degree of
      conservation. Therefore, we turned to D. hydei where a Hairless mutation has been
      described before. The D. hydei Hairless orthologue is reasonably well conserved
      with regard to gene structure and expression. The prospective Hairless protein
      orthologues share several highly conserved regions which are separated by quite
      diverged stretches. As to be expected, the largest region of high conservation
      corresponds to the Su(H) binding domain. This region is also functionally
      conserved, since this D. hydei protein domain binds very strongly to the D.
      melanogaster Su(H) protein. The other conserved regions support our earlier
      structure-function analysis since they nicely correspond to previously defined,
      functionally important protein domains. Most notably, the very C-terminal domain
      which is very sensitive to structural alterations, is nearly identical between
      the two species. In summary, this evolutionary study improves the knowledge on
      functionally significant domains of the Hairless protein, and may be helpful for
      the future identification of homologues in other animals, especially in
      vertebrates.

PMID- 10079359
TI  - High conservation of cis-regulatory elements between quail and human for the Pax
      6 gene.
AB  - The Pax-6 gene encodes a transcriptional master regulator involved in the
      development of the eye. The quail Pax-6 gene is expressed in the neuroretina from
      two promoters, P0 and P1, P0 being activated at the onset of neuronal
      differentiation. In this paper we have identified two regions in the quail Pax-6
      gene 5' flanking sequences, located 6 and 2.5 kbp upstream from the P0 promoter
      that, like the previously characterised intragenic enhancer (EP enhancer),
      function as neuroretina-specific enhancers whose activity is restricted to the P0
      promoter. Moreover, the activity of these 5' enhancers in embryonic neuroretina
      cells is weaker at day 5 than at day 7, like the EP enhancer, and parallels the
      level of expression of P0-initiated mRNAs. Footprinting experiments show that
      neuroretina-specific factors bind to these 5' enhancer elements. In addition we
      show that these quail Pax-6 enhancer elements, as well as the P0 promoter, are
      structurally and functionally conserved in humans. These results strongly suggest
      that these enhancer elements may contribute to the neuroretina-specific
      transcriptional regulation of the Pax-6 gene in vivo. Thus the complex regulation
      of the quail Pax-6 gene is also conserved in humans.

PMID- 10079360
TI  - EGF signalling regulates cell invagination as well as cell migration during
      formation of tracheal system in Drosophila.
AB  - The Drosophila tracheal system is a network of epithelial tubes that arises from
      the tracheal placodes, lateral clusters of ectodermal cells in ten embryonic
      segments. The cells of each cluster invaginate and subsequent formation of the
      tracheal tree occurs by cell migration and fusion of tracheal branches, without
      cell division. The combined action of the Decapentaplegic (Dpp), Epidermal growth
      factor (EGF) and breathless/branchless pathways are thought to be responsible for
      the pattern of tracheal branches. We ask how these transduction pathways regulate
      cell migration and we analyse the consequences on cell behaviour of the Dpp and
      EGF pathways. We find that rhomboid (rho) mutant embryos display defects not only
      in tracheal cell migration but also in tracheal cell invagination unveiling a new
      role for EGF signalling in the formation of the tracheal system. These results
      indicate that the transduction pathways that control tracheal cell migration are
      active in different steps of tracheal formation, beginning at invagination. We
      discuss how the consecutive steps of tracheal morphogenesis might affect the
      final branching pattern.

PMID- 10079361
TI  - Cloning and expression of the engrailed.a gene of the barnacle Sacculina carcini.
AB  - Cirripedia (barnacles) constitute a crustacean monophyletic taxon which is very
      well defined by several synapomorphies. In particular, all cirripedes are
      composed of six thoracic segments, but are devoid of any complete abdominal
      segment. This body plan is preserved in the adult in non-parasitic groups, while
      the parasitic rhizocephalan cirripedes completely lose arthropodian segmentation
      at the adult stage. These traits make them a particularly favourable model for
      studying the formation and maintenance of segmental identity. For the above
      reasons, it seemed worthwhile to look at the segmentation gene engrailed in a
      cirripede. A complete engrailed.a cDNA was isolated from larvae of the
      rhizocephalan cirripede Sacculina carcini. Its expression was monitored during
      larval development by use of the monoclonal antibody MAb4D9 directed against the
      Drosophila homologous proteins. The Sacculina engrailed.a gene is expressed
      during the second and third larval stages in stripes within a posterior area
      corresponding to the presumptive trunk segments. Surprisingly, these stripes
      appear in a posterior to anterior sequence. Six engrailed.a stripes characterize
      the thoracic segments of the cirripedean ground plan.

PMID- 10079362
TI  - Evolution of homeobox genes: Q50 Paired-like genes founded the Paired class.
AB  - The genes belonging to the Paired class exert primary developmental functions.
      They are characterized by six invariant amino acid residues in the homeodomain,
      while the residue at position 50 can be a serine, glutamine or lysine as in the
      Pax-type, Q50 Paired-like or the K50 Paired-like homeodomains respectively. Genes
      in this class emerged early in animal evolution: three distinct Pax genes and two
      Q50 Paired-like genes have recently been characterised from cnidarians.
      Phylogenetic molecular reconstructions taking into account homeodomain and paired
      domain sequences provide some new perspectives on the evolution of the Paired
      class genes. Analysis of 146 Paired-class homeodomains from a wide range of
      metazoan taxa allowed us to identify 18 families among the three sub-classes from
      which the aristaless family displays the least diverged position. Both Pax-type
      and K50 families branch within the Q50 Paired-like sequences implying that these
      are the most ancestral. Consequently, most Pax genes arose from a Paired-like
      ancestor, via fusion of a Paired-like homebox gene with a gene encoding only a
      paired domain; the Cnidaria appear to contain genes representing the 'before' and
      'after' fusion events.

PMID- 10079363
TI  - Origin of the chordate central nervous system - and the origin of chordates.
AB  - Contrary to traditional views, molecular evidence indicates that the protostomian
      ventral nerve cord plus apical brain is homologous with the vertebrates' dorsal
      spinal cord plus brain. The origin of the protostomian central nervous system
      from a larval apical organ plus longitudinal areas along the fused blastopore
      lips has been documented in many species. The origin of the chordate central
      nervous system is more enigmatic. About a century ago, Garstang proposed that the
      ciliary band of a dipleurula-type larva resembling an echinoderm larva should
      have moved dorsally and fused to form the neural tube of the ancestral chordate.
      This idea is in contrast to a number of morphological observations, and it is
      here proposed that the neural tube evolved through lateral fusion of a ventral,
      postoral loop of the ciliary band in a dipleurula larva; the stomodaeum should
      move from the ventral side via the anterior end to the dorsal side, which faces
      the substratum in cephalo- chordates and vertebrates. This is in accordance with
      the embryological observations and with the molecular data on the dorsoventral
      orientation. The molecular observations further indicate that the anterior part
      of the insect brain is homologous with the anterior parts of the vertebrate
      brain. This leads to the hypothesis that the two organs evolved from the same
      area in the latest common bilaterian ancestor, just anterior to the blastopore,
      with the protostome brain developing from the anterior rim of the blastopore
      (i.e. in front of the protostome mouth) and the chordate brain from an area in
      front of the blastopore, but behind the mouth (i.e. behind the deuterostome
      mouth).

PMID- 10079364
TI  - The yan gene is highly conserved in Drosophila and its expression suggests a
      complex role throughout development.
AB  - Competence for cell fate determination and cellular differentiation is under
      tight control of regulatory genes. Yan, a nuclear target of receptor tyrosine
      kinase (RTK) signaling, is an E twenty six (ETS) DNA-binding protein that
      functions as a negative regulator of cell differentiation and proliferation in
      Drosophila. Most members of RTK signaling pathways are highly conserved through
      evolution, yet no yan orthologues have been identified to date in vertebrates. To
      investigate the degree of yan conservation during evolution, we have
      characterized a yan homologue from a sibling species of D. melanogaster, D.
      virilis. Our results show that the organization, primary structure and expression
      pattern of yan are highly conserved. Both genes span over 20 kb and contain four
      exons with introns at identical positions. The areas with highest amino acid
      similarity include the Pointed and ETS domain but there are other discrete
      regions with a high degree of similarity. Phylogenetic analysis reveals that
      yan's closest relative is the human tel gene, a negative regulator of
      differentiation in hematopoetic precursors. In both species, Yan is dynamically
      expressed beginning as early as stage 4/5 and persisting throughout
      embryogenesis. In third instar larvae, Yan is expressed in and behind the
      morphogenetic furrow of the eye imaginal disc as well as in the laminar precursor
      cells of the brain. Ovarian follicle cells also contain Yan protein. Conservation
      of the structure and expression patterns of yan genes strongly suggests that
      regulatory mechanisms for their expression are also conserved in these two
      species.

PMID- 10079365
TI  - Dynamic features of adherens junctions during Drosophila embryonic epithelial
      morphogenesis revealed by a Dalpha-catenin-GFP fusion protein.
AB  - Cell-cell adherens junctions (AJs), comprised of the cadherin-catenin adhesion
      system, contribute to cell shape changes and cell movements in epithelial
      morphogenesis. However, little is known about the dynamic features of AJs in
      cells of the developing embryo. In this study, we constructed Dalpha-catenin
      fused with a green fluorescent protein (Dalpha-catenin-GFP), and found that it
      targeted apically located AJ-based contacts but not other lateral contacts in
      epithelial cells of living Drosophila embryos. Using time-lapse fluorescence
      microscopy, we examined the dynamic performance of AJs containing Dalpha-catenin
      GFP in epithelial morphogenetic movements. In the ventral ectoderm of stage 11
      embryos, concentration and deconcentration of Dalpha-catenin-GFP occurred
      concomitantly with changes in length of AJ contacts. In the lateral ectoderm of
      embryos at the same stage, dynamic behaviour of AJs was concerted with division
      and delamination of sensory organ precursor (SOP) cells. Moreover, changes in
      patterns of AJ networks during tracheal extension could be followed. Finally, we
      utilized Dalpha-catenin-GFP to precisely observe the defects in tracheal fusion
      in shotgun mutants. Thus, the Dalpha-catenin-GFP fusion protein is a helpful tool
      to simultaneously observe morphogenetic movements and AJ dynamics at high spatio
      temporal resolution.

PMID- 10079366
TI  - Development of the musculature in the limpet Patella (Mollusca,
      Patellogastropoda).
AB  - Whole-mount technique using fluorescent-labelled phalloidin for actin staining
      and confocal laser scanning microscopy as well as semi-thin serial sectioning,
      scanning and transmission electron microscopy were applied to investigate the
      ontogeny of the various muscular systems during larval development in the limpets
      Patella vulgata L. and P. caerulea L. In contrast to earlier studies, which
      described a single or two larval shell muscles, the pretorsional trochophore-like
      larva shows no less than four different muscle systems, namely the asymmetrical
      main head/foot larval retractor muscle, an accessory larval retractor with
      distinct insertion area, a circular prototroch/velar system, and a plexus-like
      pedal muscle system. In both Patella species only posttorsional larvae are able
      to retract into the shell and to close the aperture by means of the operculum.
      Shortly after torsion the two adult shell muscles originate independently in
      lateral positions, starting with two fine muscle fibres which insert at the
      operculum and laterally at the shell. During late larval development the main
      larval retractor and the accessory larval retractor become reduced and the velar
      muscle system is shed. In contrast, the paired adult shell muscles and the pedal
      muscle plexus increase in volume, and a new mantle musculature, the tentacular
      muscle system, and the buccal musculature arise. Because the adult shell muscles
      are entirely independent from the various larval muscular systems, several
      current hypotheses on the ontogeny and phylogeny of the early gastropod muscle
      system have to be reconsidered.

PMID- 10079367
TI  - Role of a 461-bp G-rich repetitive element in H19 transgene imprinting.
AB  - The molecular mechanism leading to the imprinted expression of genes is poorly
      understood. While no conserved cis-acting elements have been identified within
      the known loci, many imprinted genes are located near directly repetitive
      sequence elements, suggesting that such repeats might play a role in imprinted
      gene expression. The maternally expressed mouse H19 gene is located approximately
      1.5 kb downstream from a 461-bp G-rich repetitive element. We have used a
      transgenic model to investigate whether this element is essential for H19
      imprinting. Previous results demonstrated that a transgene, which contains 14 kb
      of H19 sequence, exhibits parent-of-origin specific expression and methylation
      analogous to the endogenous H19 imprinting pattern. Here, we have generated
      transgenes lacking the G-rich repeat. One transgene, containing a deletion of the
      G-rich repetitive element but which includes an additional 1.7 kb of 5' H19
      sequence, is imprinted similarly to the endogenous H19 gene. To determine whether
      the G-rich repeat is conserved in other imprinted mammalian H19 homologues,
      additional 5' flanking sequences were cloned from the rat and human. This element
      is conserved in the rat but not in human DNA. These results suggest that the 461
      bp G-rich repetitive element is not essential for H19 imprinting.

PMID- 10079368
TI  - Intercalary muscle cell renewal in planarian pharynx.
AB  - Planarian cell renewal is achieved as a result of proliferation and
      differentiation of totipotent undifferentiated cells called neoblasts. The
      absence of mitosis within the planarian pharynx raises the question as to how
      cell renewal and growth occur within this organ. Two explanations have been
      advanced: one proposes that new cells remain close to the base of the pharynx,
      which then grows by distal displacement of older cells, and the other suggests
      that the new cells are intercalated between older cells throughout the pharynx.
      The second alternative, however, does not explain how new cells enter the pharynx
      or how they reach their final destination. In this study of myosin heavy-chain
      gene expression within planarian pharynx, a row of differentiating myocytes was
      detected all along the pharynx parenchyma. According to the hybridization
      pattern, all these myocytes appeared to be at early stages of differentiation.
      These data favour an intercalary model for muscle cell renewal within the
      pharynx. According to this model, neoblasts at the base of the pharynx would
      enter the pharynx, where they would start differentiation to myocytes, move to
      the subepithelial musculature and intercalate between the old muscle cells. The
      possible application of this intercalary model to other pharynx cell types is
      also discussed.

PMID- 10079369
TI  - Sequence and developmental expression of amphioxus AmphiNk2-1: insights into the
      evolutionary origin of the vertebrate thyroid gland and forebrain.
AB  - We characterized an amphioxus NK-2 homeobox gene (AmphiNk2-1), a homologue of
      vertebrate Nkx2-1, which is involved in the development of the central nervous
      system and thyroid gland. At the early neurula stage of amphioxus, AmphiNk2-1
      expression is first detected medially in the neural plate. By the mid-neurula
      stage, expression is localized ventrally in the nerve cord and also begins in the
      endoderm. During the late neurula stage, the ventral neural expression becomes
      transiently segmented posteriorly and is then down-regulated except in the
      cerebral vesicle at the anterior end of the central nervous system. Within the
      cerebral vesicle AmphiNk2-1 is expressed in a broad ventral domain, probably
      comprising both the floor plate and basal plate regions; this pattern is
      comparable to Nkx2-1 expression in the mouse diencephalon. In the anterior part
      of the gut, expression becomes intense in the endostyle (the right wall of the
      pharynx), which is the presumed homologue of the vertebrate thyroid gland. More
      posteriorly, there is transitory expression in the midgut and hindgut. In sum,
      the present results help to support homologies (1) between the amphioxus
      endostyle and the vertebrate thyroid gland and (2) between the amphioxus cerebral
      vesicle and the vertebrate diencephalic forebrain.

PMID- 10079370
TI  - An amphioxus Msx gene expressed predominantly in the dorsal neural tube.
AB  - Genomic and cDNA clones of an Msx class homeobox gene were isolated from
      amphioxus (Branchiostoma floridae). The gene, AmphiMsx, is expressed in the
      neural plate from late gastrulation; in later embryos it is expressed in dorsal
      cells of the neural tube, excluding anterior and posterior regions, in an
      irregular reiterated pattern. There is transient expression in dorsal cells
      within somites, reminiscent of migrating neural crest cells of vertebrates. In
      larvae, mRNA is detected in two patches of anterior ectoderm proposed to be
      placodes. Evolutionary analyses show there is little phylogenetic information in
      Msx protein sequences; however, it is likely that duplication of Msx genes
      occurred in the vertebrate lineage.

PMID- 10079372
TI  - Bcl-2 and p53 immunoprofile in Kaposi's sarcoma.
AB  - Seventy three cases of Kaposi's sarcoma (KS) from the 3 histological subtypes
      (patch, plaque and nodular) were assessed for bcl-2 and p53 protein expression.
      The aim was to determine the level of expression of these proteins in KS and in
      the different subtypes. Commercially available antibodies to bcl-2 and p53 were
      applied after both microwave and pressure cooking antigen retrieval. Bcl-2
      immunoexpression increased from the patch stage (36%) to the plaque stage (45%)
      to the nodular stage (70.83%). Better immunostaining for bcl-2 was obtained after
      pressure cooking. p53 on the other hand, was not expressed in the patch or plaque
      stages, but 54.16% of cases in the nodular stage were immunopositive. These
      results show a progression of immunoexpression of both bcl-2 and p53 from the
      early histological stages to the late tumor stage, implying that these proteins
      are upregulated late in the evolution of KS.

PMID- 10079371
TI  - Potential use of T cell receptor genes to modify hematopoietic stem cells for the
      gene therapy of cancer.
AB  - The purpose of this review is to illustrate some of the technical and biological
      hurdles that need to be addressed when developing new gene therapy based clinical
      trials. Gene transfer approaches can be used to "mark" cells to monitor their
      persistence in vivo in patients, to protect cells from toxic chemotherapeutic
      agents, correct a genetic defect within the target cell, or to confer a novel
      function on the target cell. Selection of the most suitable vector for gene
      transfer depends upon a number of factors such as the target cell itself and
      whether gene expression needs to be sustained or transient. The TCR gene transfer
      approach described here represents one innovative strategy being pursued as a
      potential therapy for metastatic melanoma. Tumor reactive T cells can be isolated
      from the tumor infiltrating lymphocytes (TIL) of melanoma patients. A retroviral
      vector has been constructed containing the T cell receptor (TCR) alpha and beta
      chain genes from a MART-1-specific T cell clone (TIL 5). Jurkat cells transduced
      with this virus specifically release cytokine in response to MART-1 peptide
      pulsed T2 cells, showing that the virus can mediate expression of a functional
      TCR. HLA-A2 transgenic mice are being used to examine whether transduced bone
      marrow progenitor cells will differentiate in vivo into mature CD8+ T cells
      expressing the MART-1-specific TCR. Expression of the human TCR alpha and beta
      chain genes has been detected by RT-PCR in the peripheral blood of HLA-A2
      transgenic mice reconstituted with transduced mouse bone marrow. Expression of
      the TIL 5 TCR genes in the peripheral blood of these mice was maintained for
      greater than 40 weeks after bone marrow reconstitution. TIL 5 TCR gene expression
      was also maintained following transfer of bone marrow from mice previously
      reconstituted with transduced bone marrow to secondary mouse recipients,
      suggesting that a pluripotent progenitor or lymphocyte progenitor cell has been
      transduced.

PMID- 10079373
TI  - Simultaneous alterations of retinoblastoma and p53 protein expression in
      astrocytic tumors.
AB  - The genetic alterations frequently involved in glial malignancies are in the
      tumor suppressor genes, Rb and p53. An altered Rb expression or p53
      overexpression is thought to indicate defective tumor suppression and
      subsequently more aggressive tumors. Therefore, to assess the alterations in the
      conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded
      sections, 64 astrocytic tumors were studied (16 astrocytomas,7 gemistocytic
      astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin
      biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be
      positive for p53 protein. Seventeen of these showed aberrant heterogenous
      staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma
      showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors,
      simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases.
      This was more commonly observed among glioblastoma cases (7/22). No statistical
      difference was found between the survival rate of heterogenous pRb and p53
      positivity in different grades of tumors. In glioblastomas, the survival rate
      appeared to be less in patients expressing heterogenous pRb, but this was not
      statistically significant. These results lead us to suspect that p53 and pRb
      pathways are inactivated, either through mutation or as part of the neoplastic
      process in astrocytic tumors.

PMID- 10079374
TI  - Prostatic intraepithelial neoplasia and apoptosis in benign prostatic hyperplasia
      before and after the Chernobyl accident in Ukraine.
AB  - The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent
      surgery for benign prostatic hyperplasia (BPH) before and after the Chernobyl
      nuclear accident was studied. BPH samples were obtained by adenomectomy from 45
      patients operated in 1984 before the accident (Group I), and 47 patients from the
      low contaminated Kiev City (Group II) and 76 from high contaminated area (Group
      III) operated between 1996 and 1998. Their BPH samples were examined
      histologically and immunohistochemically. The incidences of prostatic
      intraepithelial neoplasia (PIN) and high grade PIN (HGPIN) were 15.5 and 11.1% in
      Group I, 29.8 and 14.9% in Grpoup II, and 35. 5 and 19.7% in Group III. The
      difference between the incidences of PIN in Group I and III is significant
      (p<0.02). There was increased apoptosis in areas of PIN in Group II and III as
      compared to Group I (p<0.001). Since apoptosis has been shown to be associated
      with ionizing radiation and it is now found to be associated with PIN in patients
      diagnosed after the Chernobyl nuclear accident, this suggests that long-term low
      dose internal ionizing radiation potentially may cause prostate cancer.

PMID- 10079375
TI  - Differential diagnostic significance of the paucity of HLA-I antigens on
      metastatic breast carcinoma cells in effusions.
AB  - Distinction between benign reactive mesothelial cells and metastatic breast
      adenocarcinoma cells in effusions from patients with a known prior history of
      breast cancer is not the easiest task in diagnostic pathology. Here, we report
      the usefulness of testing the expression of class I HLA antigens (HLA A, B, C) in
      this respect. Cytospins were prepared from effusions of patients without the
      history of breast cancer (5 cases) and from effusions of patients with
      infiltrating ductal carcinoma (11 cases). Three effusions from cancerous patients
      were not malignant cytologically. The expression of HLA-A, B, C, HLA-DR and beta2
      microglobulin as well as the macrophage antigen, CD14, was evaluated by
      immunocytochemistry. In 10 of 11 effusions the cytologically malignant cells
      expressed very weak or undetectable HLA-A,B,C as compared to the mesothelial
      cells and macrophages. The paucity of expression of HLA-A, B, C was detectable in
      those 3 cases where a definitive cytological diagnosis of malignancy could not be
      established. In contrast, mesothelial cells and macrophages from all samples were
      uniformly and strongly positive for both HLA-A, B, C and beta2-microglobulin. We
      conclude that the paucity of HLA-I antigens provides a marker helpful in
      distinguishing metastatic breast carcinoma cells from reactive mesothelial cells
      in effusions.

PMID- 10079376
TI  - Histopathologic features and expression of Bcl-2 and p53 proteins in primary
      gastric lymphomas.
AB  - The aim of this study is to present a histopathologic and immunohistochemical
      analysis of primary gastric lymphomas which were reclassified according to the
      concept of mucosa associated lymphoid tissue (MALT). The resected specimens from
      41 patients with primary gastric lymphoma were investigated retrospectively.
      Immunohistochemical study was done to analyze the immunophenotype and bcl-2 and
      p53 proteins expression. Twenty three of the cases had tumors mainly located in
      the antrum. Histologically, 12 were low grade and 20 were high grade B-cell
      lymphoma of MALT, 9 other B-cell nonHodgkin's lymphomas. Helicobacter pylori was
      identified in 72% of the cases. According to Musshoff's modification, most of the
      MALT lymphoma cases had stage I or II disease. There was significant difference
      between low and high grade cases, in respect to depth of invasion in gastric
      wall. Immunohistochemically, the neoplastic cells in all MALT lymphomas expressed
      B-cell phenotype. Bcl-2 protein was found to be expressed in 59% and p53 protein
      expression was detected in 72% of cases. Among the B-cell lymphoma of MALT, bcl-2
      positivity decreased and p53 positivity increased significantly as the
      histological grade advanced. So, an inverse correlation was observed between the
      expression of bcl-2 and p53. In conclusion, most primary gastric lymphomas are
      low or high grade B-cell MALT lymphomas and appear to arise in MALT acquired as a
      reaction to Helicobacter pylori infection. Expression of bcl-2 and p53 in gastric
      lymphomas may be associated with transformation from low-grade to high-grade
      disease.

PMID- 10079377
TI  - p53 and p16INK4A mutations during the progression of glomus tumor.
AB  - Glomus tumors are significantly rare tumors of carotid body. The great majority
      of these tumors are benign in character. Here we present two brothers with
      hereditary glomus jugulare tumor who had consanguineous parents. Radiotherapy was
      applied approximately 8 and 10 years ago for treatment in both cases. Eight years
      later, one of these cases came to our notice due to relapse. The mutation pattern
      of p53, p57KIP2, p16INK4A and p15NK4B genes which have roles in the cell cycle,
      was analyzed in tumor samples obtained from the two affected cases in the initial
      phase and from one of these cases at relapse. The DNA sample obtained from the
      case in initial diagnosis phase revealed no p53, p57KIP2, p16INK4A or p15INK4B
      mutation. He is still in remission phase. Despite the lack of p53, p57KIP2,
      p16INK4A and p15INK4B mutation at initial diagnosis the tumor DNA of the other
      case in relapse revealed p53 codon 243 (ATG-->ATC; met-->ile) and p16 codon 97
      (GAC-->AAC; asp-->asn) missense point mutations. No loss of heterozygosity in p53
      and p16INK4A was observed by microsatellite analysis of tumoral tissues in these
      cases. P53 and p16INK4A mutations observed in relapse phase were in conserved
      regions of both genes. No previous reports have been published with these
      mutations in glomus tumor during progression. The mutation observed in this case
      may due to radiotherapy. In spite of this possibility, the missense point
      mutations in conserved region of p53 and p16INK4A genes may indicate the role of
      p53 and p16INK4A in tumor progression of glomus tumors.

PMID- 10079378
TI  - Spectrofluorimetric detection of DMBA-induced mouse skin carcinoma.
AB  - An attempt has been made to evaluate the normal and cancer blood samples of 7,12
      dimethylbenz(a)anthracene (DMBA)-induced mouse skin carcinoma by
      spectrofluorimetric method. Analysis of acetone extracts of plasma, erythrocyte
      and erythrocyte membrane showed an alteration around 630 nm when excited at 400
      nm by cancer samples, compared to normal samples. The ratio of fluorescent
      intensity at 530 nm/630 nm was found to be decreased in erythrocyte and plasma
      and increased in erythrocyte membrane. These changes are not detectable in both
      hemolysates. It has been suggested that erythrocytes may be the carriers of
      fluorophors that accumulate in cancer tissue and may be useful in the diagnosis
      and treatment of malignancies.

PMID- 10079379
TI  - Radiation induced endothelial cell retraction in vitro: correlation with acute
      pulmonary edema.
AB  - We determined the effects of low dose radiation (<200 cGy) on the cell-cell
      integrity of confluent monolayers of pulmonary microvascular endothelial cells
      (PMEC). We observed dose- and time-dependent reversible radiation induced
      injuries to PMEC monolayers characterized by retraction (loss of cell-cell
      contact) mediated by cytoskeletal F-actin reorganization. Radiation induced
      reorganization of F-actin microfilament stress fibers was observed > or =30
      minutes post irradiation and correlated positively with loss of cell-cell
      integrity. Cells of irradiated monolayers recovered to form contact inhibited
      monolayers > or =24 hours post irradiation; concomitantly, the depolymerized
      microfilaments organized to their pre-irradiated state as microfilament stress
      fibers arrayed parallel to the boundaries of adjacent contact-inhibited cells.
      Previous studies by other investigators have measured slight but significant
      increases in mouse lung wet weight >1 day post thoracic or whole body radiation
      (> or =500 cGy). Little or no data is available concerning time intervals <1 day
      post irradiation, possibly because of the presumption that edema is mediated, at
      least in part, by endothelial cell death or irreversible loss of barrier
      permeability functions which may only arise 1 day post irradiation. However, our
      in vitro data suggest that loss of endothelial barrier function may occur rapidly
      and at low dose levels (< or =200 cGy). Therefore, we determined radiation
      effects on lung wet weight and observed significant increases in wet weight
      (standardized per dry weight or per mouse weight) in < or =5 hours post thoracic
      exposure to 50 200 cGy x-radiation. We suggest that a single fraction of
      radiation even at low dose levels used in radiotherapy, may induce pulmonary
      edema by a reversible loss of endothelial cell-cell integrity and permeability
      barrier function.

PMID- 10079380
TI  - Extraneural metastasizing ependymoma of the spinal cord.
AB  - This paper reports a case of the rare entity of an extraneural metastasizing
      ependymoma of the spinal cord. The tumor which arose in the conus medullaris and
      in the cauda equina was first diagnosed in 1956 when a thoracolumbar
      myeloresection was performed. At autopsy, 40 years after the primary diagnosis, a
      massive local tumor recurrence with extraneural metastases in the lungs, the
      pleura, the liver, and the thoracal and abdominal lymph nodes were found.
      Immunohistochemical stains of the extraneural metastases showed a strong
      cytoplasmatic expression of glial fibrillary acidic protein (GFAP). Neither the
      primary tumor nor its metastases showed any of the conventional morphological
      criteria of malignancy. Reviewing the literature we discuss the possible
      mechanism of extraneural tumor spread and the incidence of metastases with regard
      to the tumor type.

PMID- 10079381
TI  - Primary endometrioid carcinoma of fallopian tube. Clinicomorphologic study.
AB  - Twenty cases of primary Fallopian tube endometrioid carcinoma (PFTEC) are
      presented in the paper. This accounts for 42.5% of all histologic forms of
      primary Fallopian tube carcinoma (PFTC) found in our Department. The youngest
      patient was 38, and the oldest 68 years (mean: 56 years). Seven patients were
      nulliparas. Only two cases were bilateral. According to FIGO staging, 13 cases
      were evaluated as stage I, 4 as II, and 3 as stage III. Due to the histologic
      grading, 8 tumors were classified as well, 7 as moderately, and 5 as poorly
      differentiated. In the time of preparation of the manuscript, 12 women were still
      alive, 2 of them with recurrent disease. The follow-up of patients without
      recurrence ranged from 4 to 120 months (median: 63). Eight patients had died
      (survival time: from 4 to 65 months; median: 26). Metastases were found in 8
      patients, especially to ovaries. In 14/20 cases of PFTEC various forms of tubal
      wall invasion were observed. Blood or lymphatic vessels involvement was found in
      9 patients. Six of them had died and one is alive with the symptoms of disease.
      Immunohistochemical detection of the mutant form of p53 protein and oncogene
      product, c-erbB-2, was studied in 17 cases. Nine patients exhibited simultaneous
      p53 protein accumulation and c-erbB-2 expression. 2/9 of these patients are alive
      with recurrent tumors and 4/9 died. Endometrioid carcinoma of the Fallopian tube
      can be characterized by a tendency to superficial invasion of tubal wall and in a
      half of the cases by invasion of vessels. The majority of these tumors were
      diagnosed at an early stage tumors.

PMID- 10079382
TI  - A new rapid technique for the fixation of thyroid gland surgical specimens.
AB  - One of the main diagnostic problems in thyroid pathology is to distinguish
      between follicular adenoma and follicular carcinoma. Thorough sampling of the
      nodule's capsule is recommended in order to identify capsular invasion. However,
      during the hardening of the tissue, by the usual fixatives the capsule shrinks
      and rolls downwards and sometimes the capsule separates from the remaining
      tissue. The present work evaluates the use of "Lymph Node Revealing Solution"
      (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to
      that of formalin. Fifty-one unselected consecutive cases of thyroid nodules,
      which included various benign and malignant lesions, were examined. Each specimen
      was cut in two equal parts; one was fixed in LNRS, the other in formalin.
      Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of
      the tissue, and excellent immunostains. Its advantage over formalin is the
      conservation of the natural relationship between the capsule and the rest of the
      tissue, on the same plane, as well as the short time required for the final
      diagnosis.

PMID- 10079383
TI  - Human herpesvirus 8 in hematologic diseases.
AB  - Human herpesvirus type 8 (HHV-8), also known as Kaposi's sarcoma-associated
      herpesvirus (KSHV) is a new member of the g-herpesvirus family. It is an unusual
      herpesvirus in that it carries a large number of genes that encode oncoproteins
      or cell signaling proteins. In addition to being the causative agent of both HIV
      associated and non-HIV-associated Kaposi's sarcoma this DNA tumor virus has been
      implicated in the pathogenesis of several diseases. These include multiple
      myeloma (MM), Waldenstom's macroglobulinemia (WM), multicentric Castleman's
      disease (MCD), body cavity-based lymphoma (BCBL), and various other conditions
      such as sarcoidosis and pemphigus. While the causative role of the viral
      infection is fairly certain in the development of BCBL and multicentric
      Castleman's disease, HHV-8 may act through a different mechanism to induce plasma
      cell malignancies. It has been suggested though the finding is still
      controversial - that infection of bone marrow stromal dendritic cells by HHV-8
      might be a key factor in the etiology and pathogenesis of monoclonal
      gammopathies. The aim of this review is to provide a short introduction into the
      tumorigenic potential of HHV-8 as well as to detail the available data and
      possible mechanisms on the involvement of this virus in different hematologic
      diseases.

PMID- 10079384
TI  - Primary hepatic carcinoid in a renal transplant patient.
AB  - There seems to be a world-wide increase in the incidence of tumors among
      immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23
      years at the Department of Transplantation and Surgery, 56 cases were malignant
      tumors. The case of a 58-year-old female patient is reported, with disseminated
      primary carcinoid in the liver detected 86 days after renal transplantation.
      According to the literature only 39 patients with primary liver carcinoids have
      been reported until 1997, but this is the first where the carcinoid developed in
      an immunosuppressed patient. The rapid progression of the carcinoid could be
      associated with the immunosuppression.

PMID- 10079385
TI  - Flexible modelling in survival analysis. Structuring biological complexity from
      the information provided by tumor markers.
AB  - The aim of the present article is to introduce and discuss the problem of optimal
      modelling of the prognostic information provided by putative prognostic
      variables, possibly measured on a quantitative scale. A number of methodological
      aspects will be treated, with particular reference to the role of spline
      functions and artificial neural networks, which will be discussed in the context
      of the analysis of survival data. The problem of the evaluation and the choice of
      the optimal statistical models will be examined, with particular attention to the
      critical aspects related to the definition of prognostic indexes on the basis of
      the results of the selected models. Clinical examples in breast cancer on the
      evaluation of the prognostic impact of several tumor markers are provided. This
      paper is addressed to all researchers who are interested in the evaluation of the
      prognostic role of tumor markers, therefore we will stress the necessity of
      integrating the methodologies of biological, clinical and statistical research in
      the assessment of prognosis.

PMID- 10079386
TI  - How tumor markers are used in the routine follow-up of breast and colorectal
      cancer. A survey of 29 Italian hospitals.
AB  - The impact of tumor markers on the outcome of several malignancies is still under
      debate. This relative uncertainty leads to a subjective approach to their use.
      Monitoring the use of tumor markers is a valuable tool to identify the need for
      educational policies. We conducted a survey to evaluate how tumor markers are
      routinely used in the follow-up of patients with breast, colorectal and ovarian
      carcinoma. The former two malignancies are considered in the present paper. We
      surveyed 35 Italian hospitals; 29 (83%, accounting for 26,622 hospital beds)
      filled in and returned the questionnaire. Overall, 467,361 tumor marker requests
      were scrutinized by the surveyed hospitals. We found a wide variability in the
      type and number of routinely used markers, the cutoff points chosen, and the
      clinical decisions taken on the basis of marker results. In addition, we observed
      a relative lack of communication between clinicians and clinical pathologists in
      around 50% of the surveyed hospitals. In these cases clinical information was not
      provided to the laboratory and methodological aspects were not communicated to
      clinicians. From the findings of the present study we conclude that the
      cooperation between clinicians and clinical pathologists must improve before
      guidelines for the use of tumor marker assays can be framed and the compliance
      with these guidelines can be checked. Request forms for tumor marker assays
      should therefore be designed to contain clinical information and the quality of
      filling in request forms with clinical data should be carefully monitored.

PMID- 10079387
TI  - High levels of cathepsin B predict poor outcome in patients with breast cancer.
AB  - Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and
      metastasis. Other proteases involved in cancer spread such as urokinase-type
      plasminogen activator (uPA) and cathepsin D have previously been shown to be
      prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with
      primary breast cancer. CB levels were significantly higher in both primary and
      metastatic breast tumors than in fibroadenomas (p = 0.0001). In the primary
      carcinomas, CB levels showed no significant correlation with either nodal status,
      tumor size or estrogen receptor (ER) status. Patients with primary breast cancers
      containing high levels of CB had a significantly shorter disease-free interval (p
      = 0.01, chi-square = 6.61) and overall survival (p = 0.014, chi-square = 6.08)
      than patients with low levels of the protease. However, in multivariate analysis,
      using nodal status, tumor size, ER status and urokinase plasminogen activator
      (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER
      status and uPA were prognostic in multivariate analysis. In conclusion, CB, like
      certain other proteases implicated in cancer metastasis, correlates with poor
      outcome in patients with breast cancer. These results thus support the evidence
      from model systems linking CB to cancer spread. Inhibition of CB expression or
      activity might therefore be exploited for anti-metastatic therapies.

PMID- 10079388
TI  - OVX1 and CEA in patients with colon carcinoma, colon polyps and benign colon
      disorders.
AB  - The OVX1 tumor marker promises to complement CA125 for detection of early stage
      ovarian carcinoma. OVX1 has also been shown to be elevated in colon cancer
      patients. This study is designed to assess serum OVX1 levels in patients with
      specific stages of colon cancer, colon polyps or other GI disorders. Serum OVX1
      and CEA were measured by radioimmunoassay or enzyme immunoassay for 206 patients
      at the time of colonoscopy or staging for colon carcinoma. In patients with stage
      I, II, III, or IV colon carcinoma, serum OVX1 was positive in 37%, 48%, 74% and
      63%, respectively. Fifty-three percent of patients with colon polyps had elevated
      OVX1 levels, while OVX1 levels were positive in only 7% of healthy controls. If
      both OVX1 and CEA were considered, at least one of these markers was elevated in
      36%, 60%, 79% or 89% of patients with stage I, II, III or IV colon carcinoma,
      respectively. The majority of patients with inflammatory bowel disease or
      diverticulosis also had elevated OVX1 levels. Both markers were positive in 27%
      of patients with colon carcinoma, and not in any patients with a normal
      colonoscopy or with a diagnosis of diverticulosis or hemorrhoids. In conclusion,
      serum OVX1 improves the sensitivity of CEA for detecting colon polyps and colon
      cancer; however, the use of OVX1 in this setting is hindered by its elevation in
      non-malignant colonic processes.

PMID- 10079389
TI  - Neuron-specific enolase in non-neoplastic lung diseases, a marker of hypoxemia?
AB  - Neuron-specific enolase (NSE) is a glycolytic enzyme localized within neuronal
      and neuroendocrine tissues. Serum NSE is widely used as a marker of
      neuroendocrine tumors. Moderate serum NSE elevation has been reported in some
      patients with benign lung diseases. We decided to investigate whether the
      elevation of serum NSE in non-neoplastic lung diseases is connected with
      hypoxemia and to what extent the recovery of sufficient ventilation with a
      respirator may influence NSE concentrations. Serum NSE was estimated by means of
      radioimmunoassay in 83 patients with various non-neoplastic lung diseases. Serum
      NSE exceeding 12.5 micrograms/L was significantly more frequent in patients with
      marked hypoxemia (PaO2 < 6.67 kPa; p = 0.03) than in others. The median NSE value
      in the group of patients without respiratory failure (Ro) was 7.2 micrograms/L
      (10% > 12.5 micrograms/L), in the group of patients with respiratory failure not
      requiring mechanical ventilation (Rf) it was 8.5 micrograms/L (24% > 12.5
      micrograms/L), and in the group of patients with respiratory failure requiring
      mechanical ventilation (Rfv) 13.1 micrograms/L (60% > 12.5 micrograms/L). The
      differences between the Rfv group and the other two groups (Rf and Ro) were
      significant (P = 0.049 and p = 0.0004, respectively). During successful
      mechanical ventilation elevated serum NSE decreased to values below the cutoff in
      8/10 patients. We conclude that serum NSE elevation is a frequent event in
      patients with terminal hypoxemia in the course of benign lung diseases.
      Normalization of serum NSE is observed in the majority of patients during the
      first week of mechanical ventilation.

PMID- 10079390
TI  - Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid
      neoplasms: selective deficiency in metastatic disease.
AB  - Several endogenous hormones have been proven to stimulate cancer growth, whereas
      at present very few hormones are known to display oncostatic activity. The most
      widely investigated antitumor hormone is the pineal indole melatonin (MLT), and
      cancer progression has been shown to be associated with a decline in MLT
      secretion. Recently, another hormone, the adrenal steroid dehydroepiandrosterone
      sulfate (DHEAS), has appeared to exert antitumor effects similar to those
      previously described for MLT. In addition, experimental studies suggest a
      diminished DHEAS production with neoplastic progression. This preliminary study
      was performed to evaluate the daily secretion of DHEAS in a group of early and
      advanced cancer patients. The study included 70 patients with solid tumors
      (gastrointestinal tract tumors: 28; breast cancer: 24; non-small cell lung
      cancer: 18), 28 without and 42 with distant metastases. The serum levels of DHEAS
      were measured by RIA in blood samples collected in the morning. The control group
      consisted of 100 age- and sex-matched healthy subjects. No significant difference
      in mean serum levels of DHEAS was observed between controls and non-metastatic
      patients. In contrast, metastatic patients, irrespectively of tumor histotype,
      showed significantly lower mean levels of DHEAS with respect to either controls
      or non-metastatic patients. Moreover, metastatic patients with visceral locations
      showed significantly lower values of DHEAS than those with bone or soft-tissue
      metastases. This preliminary study would suggest there to be a deficiency in the
      daily DHEA secretion in patients with disseminated cancer. Further studies
      evaluating circadian DHEAS secretion in relation in that of the pineal hormone
      MLT will be required to better define the biological significance of the advanced
      cancer-related decline in endogenous DHEAS production.

PMID- 10079391
TI  - Preoperative carbohydrate antigen 195 (CA195) and CEA serum levels as prognostic
      factors in patients with colorectal cancer.
AB  - We evaluated in 214 patients with primary colorectal cancer the prognostic value
      of the preoperative serum levels of CEA and CA195. For CEA these levels were
      above the cutoff of 6 ng/ml in 31.3% of patients, whereas for CA195 they were
      higher than 12 U/ml in 35.9% of patients. The simultaneous use of both antigens
      increased the sensitivity to 49%, which was significantly higher than that of CEA
      (p < 0.001) and CA195 (p < 0.01) taken singly. The mean preoperative CEA levels
      were significantly (p < 0.001) correlated with Dukes' stage only, while there was
      a significant correlation between preoperative serum levels of CA195 and Dukes'
      stage (p < 0.001), grade of differentiation (p < 0.01) and tumor location (p <
      0.05). The results indicated that high preoperative serum levels of CEA and CA195
      were associated with a shorter overall survival (p < 0.0001). In addition,
      separate Cox multivariate analysis showed that preoperative CA195 was, after
      Dukes' stage, the strongest factor to predict overall survival (p < 0.0001).

PMID- 10079392
TI  - Gonadotropin levels in ovarian cyst fluids: a predictor of malignancy?
AB  - Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding
      LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of
      elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not
      lead to growth restriction, which means that serum levels of gonadotropins may
      not play the most important role in ovarian cancer. We therefore analyzed the LH
      and FSH concentrations in cyst fluids of ovarian cancer. Patients with
      preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum
      samples of the patients were obtained during surgery, while the fluids within the
      cysts were aspirated after surgical removal of the tumor. FSH and LH levels in
      serum and cyst fluids were measured using single antibody EIA (Boehringer
      Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated.
      While there were no significant differences in the FSH and LH serum
      concentrations, highly significant differences in the FSH and LH levels in cyst
      fluids were found. Only cancer cysts contained FSH and LH, while the
      corresponding concentrations in benign cysts were always below the measuring
      range of the assays. This clear division between high gonadotropin levels in
      cysts of serous ovarian cancer and low or absent concentrations in benign ovarian
      tumors further supports the hypothesis that FSH and LH may play a role in ovarian
      cancer; however, explanations for this surprising finding are still lacking.

PMID- 10079393
TI  - Blood concentrations of interleukin-15 in cancer patients and their variations
      during interleukin-2 immunotherapy: preliminary considerations.
AB  - In addition to the better known cytokines IL-2 and IL-12, IL-15, which is mainly
      produced by macrophages, is a new antitumor cytokine with a mechanism of action
      similar to that of IL-2. At present, however, there are no data about IL-15
      secretion in cancer patients. This study was carried out to evaluate IL-15 blood
      concentrations in patients with early or advanced cancer and their possible
      variations in response to IL-2 cancer immunotherapy. The study included 40
      patients with solid tumors, 24 of whom had metastatic disease. In addition, IL-15
      secretion was evaluated during subcutaneous low-dose IL-2 therapy (6 million
      IU/day for 6 days/week for 4 weeks) in 14 metastatic renal cell cancer patients
      by collecting blood samples at weekly intervals. The control group consisted of
      40 age-matched healthy subjects. Serum levels of IL-15 were measured by an enzyme
      immunoassay. No significant difference in mean serum levels of IL-15 was observed
      between cancer patients and controls. Moreover, the mean serum levels of IL-15
      found in metastatic cancer patients were not significantly different from those
      found in patients with limited disease. Finally, no significant changes in mean
      levels of IL-15 occurred during IL-2 cancer immunotherapy. This preliminary study
      would suggest that IL-15 secretion is substantially within the normal range in
      cancer patients, both in early and advanced disease, and no variation seems to
      occur in response to IL-2 administration.

PMID- 10079394
TI  - Impaired ex vivo production of TNF-alpha by whole blood cells in the presence of
      PSA.

PMID- 10079395
TI  - Transforming growth factor beta 2 (TGF beta 2) and dehydroepiandrosterone
      sulphate (DHEAs) levels in breast macrocyst fluids. Different behaviour according
      to cyst type.

PMID- 10079396
TI  - The political economy of the welfare state in developed capitalist countries.
AB  - The article analyzes the social, economic, and political changes taking place in
      developed capitalist countries that are affecting their welfare states, in
      particular the changes in the family, in people's life cycles, in economic and
      social structures, and, most importantly, in the political contexts. The author
      shows how these changes take place and how the ways in which various countries
      respond to them depend mainly on the correlation of forces (of which class forces
      continue to be of great importance) and their expression in the political space.
      The dominant theoretical frame (promoted by international agencies and many
      governments) assumes that all governments, regardless of their political
      coloration, are forced to follow the same policies because of the need to be
      competitive in the globalized economy, where international markets (whether
      financial or commercial) determine what governments can and must do. Questioning
      this economic determinism, the article recovers the importance of politics,
      putting politics at the center of the explanation of what is happening in the
      welfare states of the developed capitalist countries, including the neoliberal
      aggression against them.

PMID- 10079397
TI  - Ravaging the poor: the International Monetary Fund indicted by its own data.
AB  - Recent International Monetary Fund studies on the impact of its structural
      adjustment programs on the poorest nations reveal that most have stagnated or
      declined economically. The IMF's requirement that these countries increase
      exports despite falling world commodity prices has been a principal cause of
      their economic malaise. Meanwhile, IMF loan conditions demanding lower government
      expenditures have led to sharp reductions in general social spending, from which
      the wealthiest quintile of the population receives a disproportionately larger
      share of outlays for health and education.

PMID- 10079398
TI  - Income inequality, social cohesion, and class relations: a critique of
      Wilkinson's neo-Durkheimian research program.
AB  - Wilkinson's "income inequality and social cohesion" model has emerged as a
      leading research program in social epidemiology. Public health scholars and
      activists working toward the elimination of social inequalities in health can
      find several appealing features in Wilkinson's research. In particular, it
      provides a sociological alternative to former models that emphasize poverty,
      health behaviors, or the cultural aspects of social relations as determinants of
      population health. Wilkinson's model calls for social explanations, avoids the
      subjectivist legacy of U.S. functionalist sociology that is evident in "status"
      approaches to understanding social inequalities in health, and calls for broad
      policies of income redistribution. Nevertheless, Wilkinson's research program has
      characteristics that limit its explanatory power and its ability to inform social
      policies directed toward reducing social inequalities in health. The model
      ignores class relations, an approach that might help explain how income
      inequalities are generated and account for both relative and absolute
      deprivation. Furthermore, Wilkinson's model implies that social cohesion rather
      than political change is the major determinant of population health. Historical
      evidence suggests that class formation could determine both reductions in social
      inequalities and increases in social cohesion. Drawing on recent examples, the
      authors argue that an emphasis on social cohesion can be used to render
      communities responsible for their mortality and morbidity rates: a community
      level version of "blaming the victim." Such use of social cohesion is related to
      current policy initiatives in the United States and Britain under the New
      Democrat and New Labor governments.

PMID- 10079399
TI  - The effects of outsourcing on occupational health and safety: a comparative study
      of factory-based workers and outworkers in the Australian clothing industry.
AB  - Outsourcing has become increasingly widespread throughout industrialized
      societies over the past 20 years. Accompanying this has been a renewed growth in
      home-based work, sometimes using new technologies (telework) but also entailing a
      re-emergence of old forms, such as clothing outwork, used extensively 100 years
      ago. A growing body of research indicates that changes to work organization
      associated with outsourcing adversely affect occupational health and safety
      (OHS), both for outsourced workers and for those working alongside them. This
      study assessed the OHS implications of the shift to home-based workers in the
      Australian clothing industry by systematically comparing the OHS experiences of
      100 factory-based workers and 100 outworkers. The level of self-reported injury
      was over three times higher among outworkers than factory-based workers
      undertaking similar tasks. The most significant factor explaining this difference
      was the payment system. All outworkers were paid solely by the piece, whereas
      factory workers were paid either under a time plus production bonus system or
      solely on a time basis. While the incidence of injury was far higher among
      outworkers, factory-based workers paid under an incentive system reported more
      injuries than those paid solely on a time basis. Increasing injury was correlated
      with piecework payment systems.

PMID- 10079400
TI  - The unwritten story of women's role in the birth of occupational health and
      safety legislation.
AB  - Women's role in the formation of trade unions and development of collective
      bargaining, as well as in labor's historical struggle to improve day-to-day
      working conditions, has been conspicuously underplayed, if not ignored. Yet, when
      one reviews the history of the reduction of working hours, prohibition of child
      labor, elimination of homework in tenement slums, reform of factory legislation,
      and investigations into accidents precipitating early workers' compensation
      legislation, the literature is rich with women's investigative reports and
      studies on unhealthy and unsafe working conditions. This was the case from the
      late 19th century in North America up until the 1950s and the Cold War. The
      women's movement and political activities requiring factory reforms then seemed
      to go underground, re-emerging in full force during the 1960s. Women's
      involvement in the environmental movement, especially in the United States, has
      been significant in politicizing occupational health as well. Their efforts led
      to the 1970 passage of the U.S. Occupational Health and Safety Act.

PMID- 10079401
TI  - One-eyed science: scientists, workplace reproductive hazards, and the right to
      work.
AB  - Although most occupational health research has been done with male subjects and
      on jobs traditionally done by men, research on reproductive hazards is an
      exception. Researchers were late to realize that men were exposed to reproductive
      hazards. However, women's health problems have been excluded from the large
      scientific literature on reproductive hazards, which has concentrated on hazards
      to fetuses. This is true even of much feminist-oriented research. This neglect is
      attributable to a reluctance to emphasize health hazards for women at work, since
      identifying those specific to women may militate against women's employment.
      Union action is in fact necessary to protect access to employment and health at
      the same time.

PMID- 10079402
TI  - Hear no secrets, see no secrets, speak no secrets: secrecy in the Canadian drug
      approval system.
AB  - Systemic bias in the form of a lack of transparency in the operation of the
      Canadian drug regulatory agency, the Health Protection Branch, seriously
      undermines our knowledge of how well the agency is functioning. In recent years
      this secrecy has combined with deregulation, downsizing, and privatization to
      compromise safety and could lead to deleterious consequences in the way that
      drugs are being used. Finally, these forces are threatening the ability of the
      Health Protection Branch to set priorities for the overall system of drug
      regulation. This article provides concrete examples of each of these problems.
      The author then discusses why secrecy is so firmly entrenched in the regulatory
      approval system, and offers some suggestions on how to tackle this issue.

PMID- 10079403
TI  - An equitable way to pay for universal coverage.
AB  - This article describes a way to finance universal health care coverage that
      preserves much of the current financing system and replaces funds obtained from
      regressive sources with revenue from more progressive ones. New funding would be
      needed for 24 percent of health expenditures and would be raised through an
      increase in the federal personal income tax. Premiums are eliminated since their
      cost is the same to everyone regardless of income. Cost sharing and out-of-pocket
      spending for medically necessary services are also abolished. In a more equitably
      financed system, employers would pay a new payroll tax that raised the same
      amount of money they currently spend for employee health insurance premiums; this
      would require a payroll tax of about 7 percent. Revenue from an increase in
      federal personal income taxes would replace household out-of-pocket expenditures
      for medically necessary services and payments for insurance premiums. For the
      average, middle-income family, the tax increase would total $731 in 1998. In
      exchange for the tax increase, no American or American employer would need to buy
      health insurance or face out-of-pocket charges for any medically indicated health
      care.

PMID- 10079404
TI  - Hospital length of stay in the United States and Japan: a case study of
      myocardial infarction patients.
AB  - Patients in Japan stay in the hospital significantly longer than those in the
      United States. This study investigates factors that may account for the
      difference from a sociocultural perspective. In an intensive case study on
      patients with uncomplicated acute myocardial infarction at a university hospital
      in Japan and its U.S. counterpart, the authors collected data from interviews
      with patients, their families, physicians, and other medical professionals and
      from medical, nursing, and billing records. Patients with comparable medical
      conditions were studied; U.S. patients stayed in the hospital for 8.8 days on
      average, Japanese patients for 25.0 days. The average total charge of
      hospitalization was 2.3 times higher in the United States than in Japan. Although
      length of stay is determined mainly by physicians' clinical judgment and by
      health care system factors, patients and their family members often actively
      participate in decision-making about discharge dates. This case study approach
      revealed how different health care systems manifest themselves in the individual
      patient's course of illness, which cannot be examined by macro-level comparison
      of nations' health care systems.

PMID- 10079405
TI  - Does assisted reproduction make an impact on the identity and self-image of
      infertile couples?

PMID- 10079406
TI  - Does assisted reproduction make an impact on the identity and self-esteem of
      infertile women during the transition to parenthood?

PMID- 10079407
TI  - Intracytoplasmic sperm injection after follicle stimulation with highly purified
      human follicle-stimulating hormone compared with human menopausal gonadotropin.
AB  - PURPOSE: Our purpose was to compare oocyte nuclear maturation and embryo quality
      after pituitary down-regulation and ovarian stimulation with highly purified
      follicle-stimulating hormone (FSH) or human menopausal gonadotropin (HMG).
      METHODS: Fifty-five patients 37 years of age or younger who were undergoing in
      vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) were evaluated
      retrospectively. In all cases, male factor was the only indication for treatment,
      with no female-related factors identified. Following pituitary down-regulation,
      patients were stimulated with hMG (n = 20) or highly purified FSH (n = 35). Main
      outcome measures included ovarian response to stimulation, oocyte maturity, and
      ICSI fertilization results. Secondary outcome measures included pregnancy rates
      and outcome. RESULTS: The ovarian response to stimulation was similar for the two
      groups, as were the percentage of metaphase II oocytes, fertilization and
      cleavage rates, and number and quality of transferred and cryopreserved embryos.
      Cycle outcome was comparable. CONCLUSIONS: In normogonadotropic subjects,
      monocomponent therapy with highly purified FSH is as effective as hMG in
      stimulating ovarian follicular development, synchronization of oocyte maturation,
      and IVF-ICSI outcome. Our findings support the conclusion that the luteinizing
      hormone component in the stimulation protocol is unnecessary.

PMID- 10079408
TI  - Is intracytoplasmic sperm injection necessary for couples undergoing in vitro
      fertilization-embryo transfer with normal semen analyses but failing hamster egg
      penetration assays?
AB  - PURPOSE: Our purpose was to assess whether in vitro fertilization (IVF)-embryo
      transfer (ET) candidate couples with basically normal semen analyses but failing
      zona-free hamster egg penetration assay (HEPA) scores benefit from
      intracytoplasmic sperm injection (ICSI). METHODS: Twenty consecutive IVF
      candidate couples with normal-borderline semen analyses and failing HEPA scores
      were recruited. Mature oocytes obtained from each woman were randomly divided
      between ICSI (group I; n = 126 oocytes) and standard insemination techniques
      (group II; 138 oocytes). Fertilization (two pronuclei) and cleavage (2-4 cells)
      rates were assessed for both groups. RESULTS: There were no statistically
      significant differences between the two groups with respect to (mean +/- standard
      error of the mean) fertilization (group I, 63.1 +/- 7.75; group II, 77.8 +/-
      4.7%) or cleavage (group I, 87.3 +/- 2.4%; group II, 91.2 +/- 3.5%) rates.
      CONCLUSIONS: ICSI is not beneficial for IVF-ET when sperm samples demonstrate a
      failing HEPA score but have normal or minimally compromised semen analysis
      parameters.

PMID- 10079409
TI  - Expression of inhibin/activin subunits and their receptors and binding proteins
      in human preimplantation embryos.
AB  - PURPOSE: Our purpose was to study the role of inhibin/activin during
      embryogenesis. METHODS: Transcripts of inhibin/activin subunits (alpha, beta A,
      beta B), activin receptors (types I and II), and follistatin were detected by a
      reverse transcriptase-polymerase chain reaction in human reproductive cells and
      preembryos cultured alone or co-cultured with human endometrial cells. RESULTS:
      Transcripts of alpha, beta A, beta B subunits were all detected in granulosa
      luteal cells, but only beta A units were detected in endometrial stromal and
      decidualized cells. In human preimplantation embryos, none of these subunits were
      detected in embryos from the four-cell to the morula stage and only beta A
      subunits were detectable in blastocyst embryos. Activin receptors were detectable
      in all of the studied embryos and cells. Transcripts of beta A, activin
      receptors, and follistatin were differentially expressed in human preimplantation
      embryos cultured in vitro and their expressions were significantly enhanced with
      the presence of endometrial stromal cells. CONCLUSIONS: Our data suggest that
      there is a possible endometrium-embryo interaction via endometrial activins and
      preimplantation embryo receptors and that the embryonic expressions of these
      activins, their receptors, and binding proteins are dependent on embryonic stage.

PMID- 10079410
TI  - Retrieval, maturation, and fertilization of immature oocytes obtained from
      unstimulated patients with polycystic ovary syndrome.
AB  - PURPOSE: Our purpose was to determine whether immature oocytes could be retrieved
      under local anesthesia, whether these oocytes would mature and fertilize in
      vitro, and whether adequate endometrium development could be obtained after
      hormonal supplementation. METHODS: Ovum pick-up was performed under local
      anesthesia. Immature oocytes were cultured and inseminated. To prepare the
      endometrium, estradiolvalerate was administered in combination with micronized
      progesterone. RESULTS: Immature oocytes were obtained in all cases. Fifty-six
      percent (n = 30) of the oocytes developed into metaphase II (MII) after 48 hr of
      culture, and another 20% reached the MII stage by 72 hr. Normal fertilization was
      observed in only 10% of oocytes inseminated. No embryonic development occurred,
      and therefore embryo transfer was not performed in any of the patients.
      Endometrial microbiopsy was performed in all subjects and endometrial development
      was considered sufficient in eight patients. CONCLUSIONS: We collected immature
      oocytes from patients with polycystic ovary syndrome without general anesthesia.
      In vitro maturation of these oocytes seemed adequate but fertilization rates were
      poor. Sufficient endometrial quality was obtained after hormonal substitution.

PMID- 10079411
TI  - Inhibition of human sperm motility by specific herbs used in alternative
      medicine.
AB  - PURPOSE: Our purpose was to analyze sperm motility parameters in the presence of
      herbs. METHODS: Washed sperm were incubated in either saw-palmetto (Serenoa
      repens, Permixon Sabal serrulatum), echinacea purpura, ginkgo biloba, St. John's
      wort (Hypericum perforatum), or control medium. Parameters were measured on a
      Hamilton-Thorn analyzer after 1, 4, 24, and 48 hr at 37 degrees C. RESULTS: Sperm
      motility was inhibited at the high concentration (0.6 mg/mL) of St. John's wort.
      Curvilinear velocities and beat cross frequencies also decreased, but not
      hyperactivation. High-concentration saw-palmetto, echinacea, or gikgo inhibited
      motility at 24 and 48 hr. CONCLUSIONS: A potent inhibition of sperm motility was
      seen in St. John's wort unrelated to changes in pH. Furthermore, sperm viability
      was compromised in St. John's wort, suggesting a spermicidal effect. Metabolic
      changes were observed in saw-palmetto-treated sperm. High-concentration echinacea
      purpura interfered with sperm enzymes. Ginkgo did not have an antioxidant effect
      on sperm motility.

PMID- 10079412
TI  - Preimplantation diagnosis by fluorescence in situ hybridization using 13-, 16-,
      18-, 21-, 22-, X-, and Y-chromosome probes.
AB  - PURPOSE: Our purpose was to select the proper chromosomes for preimplantation
      diagnosis based on aneuploidy distribution in abortuses and to carry out a
      feasibility study of preimplantation diagnosis for embryos using multiple-probe
      fluorescence in situ hybridization (FISH) on the selected chromosomes of biopsied
      blastomeres. METHODS: After determining the frequency distribution of aneuploidy
      found in abortuses, seven chromosomes were selected for FISH probes. Blastomeres
      were obtained from 33 abnormal or excess embryos. The chromosome complements of
      both the biopsied blastomeres and the remaining sibling blastomeres in each
      embryo were determined by FISH and compared to evaluate their preimplantation
      diagnostic potential. RESULTS: Chromosomes (16, 22, X, Y) and (13, 18, 21) were
      selected on the basis of the high aneuploid prevalence in abortuses for the
      former group and the presence of trisomy in the newborn for the latter. Thirty
      six (72%) of 50 blastomeres gave signals to permit a diagnosis. Diagnoses made
      from biopsied blastomeres were consistent with the diagnoses made from the
      remaining sibling blastomeres in 18 embryos. In only 2 of 20 cases did the
      biopsied blastomere diagnosis and the embryo diagnosis not match. CONCLUSIONS: If
      FISH of biopsied blastomere was successful, a preimplantation diagnosis could be
      made with 10% error. When a combination of chromosome-13, -16, -18, -21, -22, -X,
      and -Y probes was used, up to 65% of the embryos destined to be aborted could be
      detected.

PMID- 10079413
TI  - Enhanced hatching rate of bovine IVM/IVF/IVC blastocysts using a 1.48-micron
      diode laser beam.
AB  - PURPOSE: Our purpose was to test whether zona pellucida (ZP) drilling using a
      1.48-micron diode laser beam on bovine IVM/IVF/IVC blastocysts is effective for
      embryo hatching. METHODS: Blastocysts produced in vitro at day 7 after IVF were
      divided into control and laser-drilled groups, respectively. RESULTS: When the
      rates of in vitro development of bovine embryos were examined, the average
      cleavage rate (> or = two-cell) was 82.3% and the blastocyst rate at day 7 after
      IVF was 32.5%. Using these blastocysts, when the laser drilling effect was
      investigated at 48 hr after treatment, the total hatching rate in the laser
      drilled group (98.0%) was significantly higher than that in the control group
      (60.0%) (P < 0.001). Especially, the hatched rate of the laser-drilled group
      (68.0%) was significantly enhanced compared with that of the control group
      (30.0%) (P < 0.001). CONCLUSIONS: These results demonstrated that laser ZP
      drilling on bovine IVM/IVF/IVC blastocysts can significantly increase the
      hatching rate.

PMID- 10079414
TI  - Low oxygen inhibits but complex high-glucose medium facilitates in vitro
      maturation of squirrel monkey oocyte-granulosa cell complexes.
AB  - PURPOSE: The objectives of these in vitro maturation studies in primate cumulus
      oocyte complexes (COCs) were to evaluate the effect of a reduced-oxygen
      environment and to compare medium with a high-glucose concentration to medium
      with pyruvate but no glucose. METHODS: COCs were retrieved from squirrel monkeys
      stimulated with 1 mg of follicle-stimulating hormone (FSH) for 4-6 days.
      Experiment 1 examined maturation after 48 hr in 5% O2/5% CO2/90% N2 compared with
      5% CO2/air. The medium was CMRL-1066 containing moderate glucose (5.5 mM)
      supplemented with 1 mM glutamine, 0.33 mM pyruvate, 0.075 IU/ml human FSH, 5
      IU/ml human chorionic gonadotropin, 75 U penicillin G/ml, and 20% fetal bovine
      serum. Experiment 2 in 5% CO2/air, compared P-1 medium (pyruvate and lactate but
      no glucose) to Waymouth's medium (27.5 mM glucose), both with identical
      supplements. RESULTS: Only 3 (8%) of 37 COCs matured in 5% O2, while 39 (49%) of
      80 matured in ambient O2. Fourteen (22%) of 64 complexes matured in P-1 medium,
      compared to 47 (49%) of 96 meiosis II oocytes in Waymouth's medium (P < 0.05).
      CONCLUSIONS: These are the first primate studies showing detrimental effects of
      reduced-oxygen culture on in vitro maturation. Additionally, maturation was
      enhanced with complex high-glucose medium suggesting that the predominant
      metabolism is aerobic glycolysis.

PMID- 10079415
TI  - High-intensity strength training of patients enrolled in an outpatient cardiac
      rehabilitation program.
AB  - PURPOSE: This randomized controlled study assessed whether adding a program of
      high-intensity strength training (80% of maximum) to an outpatient cardiac
      rehabilitation program would be a safe and effective means of improving muscle
      strength and body composition. METHODS: Thirty-eight cardiac patient volunteers
      (29 men and 9 women) were randomized to either high-intensity strength training
      or flexibility training added concurrently to a 12-week outpatient cardiac
      rehabilitation aerobic exercise program. Muscle strength, local muscle endurance,
      joint flexibility, maximum treadmill tolerance time, and body composition were
      measured before and after completion of the training. RESULTS: The strength
      trained patients (n = 18) had greater increases in mean strength (90 +/- 19%
      versus 9 +/- 4%, P < 0.0001) and local muscle endurance (20 versus 6 times, P <
      0.0001), and decreases in mean perceived exertion for lifting the initial one
      repetition maximum load (11 +/- 1 versus 15 +/- 1, P < 0.0001) when compared with
      flexibility-trained patients (n = 16). The strength group lost more body fat (2.8
      +/- 2.0 versus 1.3 +/- 2.0 kg, P < 0.01), tended to gain more lean tissue (1.5 +/
      2.3 versus 0.5 +/- 1.2 kg, P < 0.10), and had greater improvements in treadmill
      time (2.3 +/- 1.3 versus 1.2 +/- 1.0 minute, P < 0.02) than did the flexibility
      group. Improvements in joint flexibility were similar for each group. None of the
      subjects had evidence of cardiac ischemia or arrhythmia during the training
      sessions. CONCLUSIONS: Medically supervised high-intensity strength training is
      well tolerated when added to the aerobic training of cardiac rehabilitation
      programs and allows patients to aggressively gain the strength and endurance they
      will need to complete daily living tasks at lower perceived efforts. Strength
      training also reduces cardiac risk factors by improving body composition and
      maximum treadmill exercise time.

PMID- 10079416
TI  - Rethinking the place of psychological support groups in cardiopulmonary
      rehabilitation.

PMID- 10079417
TI  - Effect of high- versus low-frequency exercise training in multidisciplinary
      cardiac rehabilitation on health-related quality of life.
AB  - BACKGROUND: The authors examined the importance of the frequency of aerobic
      exercise training in multidisciplinary rehabilitation in improving health-related
      quality of life in the short run in patients with documented coronary artery
      disease. METHODS: Patients (114 males and 16 females; age range, 32-70 years)
      were randomized into either a high-frequency or a low-frequency exercise training
      program (10 versus 2 sessions per week, respectively) as part of a 6-week
      multidisciplinary cardiac rehabilitation program. The General Health
      Questionnaire and the RAND-36 were used to assess changes in psychological
      distress and subjective health status. RESULTS: After 6 weeks, high-frequency
      patients reported significantly more positive, change in "psychological distress"
      (P < 0.05), "mental health" (P = 0.05), and "health change" (P < 0.01), than low
      frequency patients. Apart from changes in mean scores, individual effect sizes
      indicated that a significantly greater percentage of high-frequency patients
      experienced substantial improvements in "psychological distress" (P < 0.01),
      "physical functioning" (P < 0.05), and "health change" (P < 0.05), compared with
      low-frequency patients. In addition, deterioration of quality of life was
      observed in a considerable number of high-frequency patients (ranging from 1.7%
      to 25.8% on the various measures). CONCLUSIONS: The frequency of aerobic exercise
      has a positive, independent effect on psychological outcomes after cardiac
      rehabilitation. However, this benefit after high-frequency rehabilitation appears
      to be limited to a subgroup of patients. Further investigation is required to
      identify these patients. Results provide input into recent controversies
      regarding the role of exercise training in cardiac rehabilitation.

PMID- 10079418
TI  - Goal attainment in a randomized controlled trial of rehabilitation after
      myocardial infarction.
AB  - PURPOSE: Goal setting is an established strategy in health behavior change
      programs although its usefulness remains uncertain. The authors investigate the
      validity of attainment of a patient-identified goal as an outcome measure in
      cardiac rehabilitation after myocardial infarction. METHODS: On entry into a
      randomized controlled trial of cardiac rehabilitation after an acute myocardial
      infarction, patients identified one activity that, if and when attained, would
      reflect their perception of a successful recovery. Patients reported whether they
      had attained their goal and the time of goal attainment. This was then related to
      trial outcomes that included generic and specific health-related quality of life
      and percent predicted exercise tolerance. RESULTS: Goals identified by 180 of the
      201 (89.6%) patients, were attained by 51.5% at 8 weeks and by 86.5% at 12
      months. At the end of the 8-week intervention, there was a substantial trend for
      fewer rehabilitation than usual care patients to have attained their identified
      goal (P < 0.06), although rehabilitation patients demonstrated greater
      improvement in specific health-related quality of life and exercise tolerance
      than usual care patients (P < 0.05). Among patients who identified a recreational
      physical activity goal (26.7%), significantly fewer (P < 0.007) rehabilitation
      than usual care patients had attained their goal at the end of the intervention
      with no differences in improvement in outcomes. CONCLUSIONS: Although improvement
      in outcomes was greater in rehabilitation patients than usual care patients at 8
      weeks, goal attainment, particularly for the recreational physical activity goal,
      was greater among usual care patients. The validity of self-identified activity
      goal attainment as a measure of the efficacy of cardiac rehabilitation is unclear
      and might give misleading results.

PMID- 10079419
TI  - Functional status in pulmonary rehabilitation participants.
AB  - PURPOSE: This study examined functional status abnormalities in pulmonary
      rehabilitation patients, its responsiveness to pulmonary rehabilitation
      intervention, and its relationship to patient characteristics and traditional
      measures of disease severity. METHODS: One hundred sixty-four men and women age
      69 years (SD +/- 8), who participated in 1 of 10 pulmonary rehabilitation
      programs in Connecticut, were studied pre- and postrehabilitation with the
      following outcome measures: (1) the 6-minute walk distance, (2) the Pulmonary
      Functional Status Scale (PFSS), and (3) in a subset of 60 subjects, health
      related quality of life was measured using the Chronic Respiratory Disease
      Questionnaire (CRDQ). Patient characteristics were compared to baseline values of
      these measures using Spearman correlations and Wilcoxon Rank Sum tests, whereas
      pre- to post-changes in outcome measures were evaluated using Wilcoxon signed
      ranks tests. Effect size, representing a standardized measure of change, was
      calculated for the PFSS. RESULTS: The mean FEV1 was 0.95 +/- 0.50 liters (38 +/-
      18% predicted). Rehabilitation resulted in significant increases in the 6-minute
      walk distance (24%, P < 0.001, the total PFSS scores [13%, P < 0.001, effect size
      1.0]) and the total CRDQ (18% P < 0.001). The prerehabilitation function subscore
      and total PFSS score correlated strongly with the 6-minute walk distance (r =
      0.76, 0.73; P < 0.001) and to a lesser degree with the FEV1 (r = 0.31, 0.33; P <
      0.001). Males scored higher baseline scores in several PFSS subscales, the total
      PFSS score, and the 6-minute walk distance; females showed more improvement in
      some of the PFSS scores. CONCLUSION: The 6-minute walk distance, the PFSS, and
      CRDQ all improved significantly with rehabilitation. Functional status, as
      measured by the PFSS is very strongly correlated with the 6-minute walk. Gender
      differences in the timed walk distance and functional status highlight the need
      to study this variable more thoroughly.

PMID- 10079420
TI  - Cigarette smoking shortens the duration of daily leisure time physical activity
      in patients with intermittent claudication.
AB  - PURPOSE: The authors determined (1) whether peripheral arterial occlusive disease
      (PAOD) patients who smoke have a reduction in either the duration or intensity of
      daily physical activities compared with nonsmoking patients, and (2) whether
      group differences in the pattern of physical activity persisted after controlling
      for potential confounding variables. METHODS: A total of 170 smokers and 201
      nonsmokers who had quit smoking for at least 1 year prior to investigation were
      studied. Physical activity patterns were measured using the Minnesota Leisure
      Time Physical Activity (LTPA) questionnaire. Patients also were characterized on
      potential covariates such as demographics, comorbid conditions, cardiovascular
      risk factors, ambulatory measures, peripheral hemodynamics, and anthropometric
      measures. RESULTS: The smokers were 37% less physically active than the
      nonsmokers (87 +/- 90 versus 139 +/- 121 kcal/day; P = 0.027). The reduced total
      LTPA in the smokers was due to a 28% shorter duration of performing activities
      (26 +/- 7 versus 36 +/- 22 min/day; P = 0.031), and a 3% lower mean intensity of
      the activities (3.3 +/- 1.0 versus 3.8 +/- 0.8 kcal/min; P = 0.038). The distance
      score on the Walking Impairment Questionnaire and the hip circumference were
      significant covariates of the LTPA measures. After adjusting for these
      covariates, the total LTPA remained 29% lower in the smokers (P = 0.039), the
      mean daily duration of LTPA remained 20% lower (P = 0.043), but the mean
      intensity of LTPA was no longer different between the groups. CONCLUSION:
      Compared with their nonsmoking counterparts, claudicants who smoke have a reduced
      total LTPA because they engage in activities of similar intensity for a shorter
      duration of time.

PMID- 10079421
TI  - Injuries and muscle soreness during the one repetition maximum assessment in a
      cardiac rehabilitation population.
AB  - BACKGROUND: Strength training (ST) may be beneficial for preservation of lean
      tissue, increasing bone mineral content, decreasing falls, and enhancing quality
      of life. Strength training is becoming an appropriate mode of exercise for
      cardiac rehabilitation (CR) patients. One method for determining optimal exercise
      intensity for safe and effective ST requires one repetition maximum (1RM)
      testing. Clinicians may be reluctant to perform 1RM testing in CR patients
      because of potential muscle soreness/injury and adverse hemodynamic responses in
      deconditioned patients. The purpose of this investigation was to perform 1RM
      testing in CR patients and determine muscle soreness/injury rate. METHODS:
      Seventy-four CR patients stratified by risk (low n = 30, intermediate n = 21,
      high n = 23) and sex (males = 55, females = 19) participated. Subject's ages
      ranged from 39 to 76 years and time from procedure ranged from 19 days to 2
      years. No patient had ever undergone 1RM testing. The method of Kraemer and Fry
      was used to assess 1RM. High-risk patients' heart rates/rhythms and blood
      pressures were monitored. Patients were evaluated for occurrence of muscle
      soreness/injury immediately after 1RM testing and on days 2 and 7 using a
      soreness scale developed by Shaw et al. Muscle soreness/injury was considered
      significant if a patient reported altering or stopping physical activities.
      RESULTS: No injury or significant muscle soreness occurred as a result of 1RM
      testing. No abnormal heart rate/rhythm or blood pressure responses occurred in
      high-risk patients. CONCLUSIONS: Results indicate that with proper technique, 1RM
      testing may be performed in CR patients without injury or significant muscle
      soreness.

PMID- 10079422
TI  - Telemedicine and cardiopulmonary rehabilitation: where do we stand?

PMID- 10079423
TI  - New approaches to trabecular surgery.

PMID- 10079424
TI  - Nonpenetrating trabecular surgery: it's worth the change.

PMID- 10079425
TI  - Aspirin intake and bleeding during cataract surgery.

PMID- 10079426
TI  - Aspirin intake and bleeding during cataract surgery.

PMID- 10079427
TI  - Etiology and avoidance of steep central islands.

PMID- 10079428
TI  - Effect of latanoprost on IOP.

PMID- 10079429
TI  - Simultaneous bilateral cataract surgery.

PMID- 10079430
TI  - Phacoemulsification cataract surgery in vitrectomized eyes.

PMID- 10079431
TI  - Proper orientation.

PMID- 10079432
TI  - Cartridge cracks during foldable intraocular lens insertion.

PMID- 10079433
TI  - Consultation section. Refractive surgical problem.

PMID- 10079434
TI  - Manual tunnel incision extracapsular cataract extraction using the sandwich
      technique.
AB  - Small incision extracapsular cataract extraction (ECCE) using the sandwich
      technique is described. After capsulorhexis, hydrodissection, and
      hydrodelineation, the endonucleus is moved into the anterior chamber and
      extracted by sandwiching it between the irrigating vectis and iris spatula. In a
      series of 37 eyes, most achieved a best corrected visual acuity of 5/10 or better
      postoperatively. Complications were posterior capsule rupture, vitreous loss, and
      transient corneal edema. Small incision ECCE using the sandwich technique is
      safe, easy, and does not require expensive instrumentation.

PMID- 10079435
TI  - Viscocanalostomy for open-angle glaucoma in black African patients.
AB  - PURPOSE: To study the clinical effectiveness of viscocanalostomy in a population
      of black African patients with open-angle glaucoma that was uncontrolled on
      medical treatment. SETTING: Department of Ophthalmology, Medical University of
      Southern Africa, Medunsa, South Africa. METHODS: In this prospective study
      viscocanalostomy was performed in 214 eyes of 157 black African patients with
      open-angle glaucoma that was poorly controlled by medical therapy. The procedure
      involves the production of superficial and deep scleral flaps. The deep flap is
      disserted to the plane of Schlemm's canal. From this plane, an intact window in
      Descemet's membrane is created by gentle pressure at the level of Schwalbe's line
      using a cellulose sponge. Aqueous humor diffuses through this window into a
      subscleral space (lake). Reflection of the inner flap unroofs Schlemm's canal,
      creating a trough leading to 2 entrances into Schlemm's canal (surgical ostia). A
      delicate cannula is introduced into the entrance of Schlemm's canal left and
      right and high-viscosity sodium hyaluronate is gently injected into the canal for
      4 to 6 mm. The deeper scleral flap is excised (deep sclerectomy) and the
      superficial flap is sutured securely using 5, 11-0 polyester fiber (Mersilene)
      sutures. High-viscosity sodium hyaluronate is then injected into the subscleral
      lake to act as a physical barrier to fibrinogen migration postoperatively.
      RESULTS: Postoperative intraocular pressure (IOP) of 22 mm Hg or less was
      achieved without medical therapy in 82.7% of eyes. If a beta blocker was added to
      the cases not achieving 22 mm Hg or less postoperatively, the success rate
      increased to 89.0%. The average follow-up was 35 months (range 6 to 64 months).
      CONCLUSION: Viscocanalostomy produced an encouraging long-term reduction in the
      IOP of black African patients with glaucoma who would otherwise have had a poor
      prognosis.

PMID- 10079436
TI  - Comparison of deep sclerectomy with collagen implant and trabeculectomy in open
      angle glaucoma.
AB  - PURPOSE: To assess the efficacy and postoperative complications of deep
      sclerectomy with collagen implant (DSCI), a nonpenetrating filtration procedure.
      SETTING: Glaucoma Unit, Department of Ophthalmology, University of Lausanne,
      Switzerland. METHODS: Forty-four eyes of 44 patients with medically uncontrolled
      open-angle glaucoma had DSCI and a matched control group of 44 patients,
      trabeculectomy. A superficial scleral flap was raised and a deep sclerectomy
      performed in the scleral bed. Schlemm's canal was opened, and the cornea was
      dissected to Descemet's membrane. At that stage, aqueous filtered through the
      remaining trabeculo-Descemet's membrane. A collagen implant was sutured radially
      in the scleral bed; the scleral flap and conjunctiva were then closed.
      Examinations were performed before surgery and postoperatively at 1 and 7 days
      and 1, 2, 3, 6, 9, 12, 15, 18, and 24 months. RESULTS: The mean follow-up was
      14.4 months +/- 6.3 (SD) (range 3 to 24 months). The mean preoperative
      intraoperative pressure (IOP) was 26.7 +/- 7.3 mm Hg. The mean postoperative IOP
      was 6.1 +/- 4.5 mm Hg at 1 day and 11.0 +/- 4.4 mm Hg at 1 week; it remained
      stable for the next 24 months. The success rate, defined as an IOP lower than
      21.0 mm Hg without medication, was 69% in the DSCI group and 57% in the
      trabeculectomy group at 24 months postoperatively (P = .047). The number of
      postoperative complications was significantly lower in the DSCI group than in the
      trabeculectomy group. CONCLUSIONS: The success rate of DSCI may be comparable to
      that of trabeculectomy, with fewer complications.

PMID- 10079437
TI  - Reticulated hyaluronic acid implant in nonperforating trabecular surgery.
AB  - PURPOSE: To evaluate experimentally and clinically the tolerance and efficacy of
      a reticulated hyaluronic acid implant in nonperforating trabecular surgery
      (NPTS). SETTING: Bascom Palmer Eye Institute, Miami, Florida, USA, and Clinique
      Sourdille and Clinique Ophtalmologique Universitaire, Nantes, France. METHODS: In
      experimental surgery, NPTS was performed with and without a hyaluronic acid
      implant in 25 rabbit eyes. In a pilot study, the results of NPTS with a
      hyaluronic acid implant in 72 human eyes were retrospectively analyzed in terms
      of visual acuity, intraocular pressure (IOP), external filtration, postoperative
      inflammation, and gonioscopy. Mean follow-up was 13.8 months (range 6 to 24
      months). RESULTS: In the experimental surgery, the rabbit eyes with the implant
      showed a different healing process than the eyes without the implant. The implant
      was slowly bioabsorbed and remnants were seen at the operative site (where the
      tissue was removed) up to day 56 postoperatively. This site was detectable at all
      histology study periods. Intraocular pressure reduction was longer in the implant
      group: greater than 5 months versus 3 weeks (P < .05). In the pilot study, visual
      acuity remained stable, IOP decreased from a mean preoperative level of 26.3 mm
      Hg +/- 5.22 (SD) to a mean postoperative level without treatment of 15.4 +/- 3.1
      mm Hg (P < .0001). No external filtration was detected in 60 eyes, a slightly
      elevated conjunctiva was noted in 12 eyes. Postoperative inflammation (laser
      flare and cell measurements) was low. Gonioscopy consistently demonstrated the
      persistence of a decompression space behind the trabeculum. CONCLUSION:
      Comparative experimental surgery results showed excellent tolerance and efficacy
      in the rabbit eyes with a hyaluronic acid implant. Clinical results, to be
      confirmed by a randomized comparative study, also showed excellent
      biocompatibility and encouraging efficacy.

PMID- 10079438
TI  - Combined surgery for cataract and glaucoma: phacoemulsification and deep
      sclerectomy compared with phacoemulsification and trabeculectomy.
AB  - PURPOSE: To compare the outcome of phacoemulsification-intraocular lens (IOL)
      implantation combined with nonperforating deep sclerectomy (P-DS) with that of
      phacoemulsification-IOL implantation combined with trabeculectomy (P-T). SETTING:
      Glaucoma Unit, Department of Ophthalmology, University of Lausanne, Switzerland.
      METHODS: This prospective study involved 60 eyes of 60 patients with cataract and
      various types of open-angle glaucoma. Thirty eyes had P-DS and 30, P-T. Follow-up
      was performed at regular intervals for up to 18 months. RESULTS: Mean follow-up
      was 12.5 months +/- 6.5 (SD) and 12.6 +/- 4.9 months for the P-DS and P-T groups,
      respectively. Mean preoperative intraocular pressure (IOP) was similar in both
      groups (24.8 +/- 5.9 mm Hg in the P-DS group and 24.6 +/- 7.2 mm Hg in the P-T
      group). There was no statistically significant difference in IOP decrease (14.2
      +/- 4.0 mm Hg in the P-DS group and 15.2 +/- 2.8 mm Hg in the P-T group). Visual
      outcome was similar in both groups. The P-DS group experienced significantly less
      inflammation (40.0% versus 83.0%; P = .0012) and hyphema (6.7% versus 36.7%; P =
      .010) than the P-T group. CONCLUSION: Deep sclerectomy combined with cataract
      surgery resulted in an IOP reduction similar to that with phacotrabeculectomy
      with the same visual outcome, but the lower complication rate makes ambulatory
      care easier.

PMID- 10079439
TI  - Effect of expandable full-size intraocular lenses on lens centration and capsule
      opacification in rabbits.
AB  - PURPOSE: To study the effects of expandable, hydrogel, full-size lenses (FSLs) on
      lens centration and posterior capsule opacification (PCO) in the rabbit model.
      SETTING: Center for intraocular Lens Research, Storm Eye Institute, Medical
      University of South Carolina, Charleston, South Carolina, USA. METHODS: Small
      FSLs designed for human eyes were implanted unilaterally in 20 rabbit eyes. Lens
      centration and PCO in these eyes were compared with those in eyes with
      conventional poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) or
      aphakia in the fellow eyes. In a second experiment, medium-size or large FSLs
      designed for rabbit eyes were implanted in 20 rabbit eyes and the results
      compared with those in eyes with conventional PMMA IOLs. Slitlamp examination of
      all eyes was performed regularly, after enucleation, gross inspection and
      microscopic studies were performed. RESULTS: Decentration of FSLs occurred in the
      presence of an anterior capsule tear or very large capsulorhexis. Posterior
      capsule opacification developed only at sites where the implanted lens was not in
      contact with the capsule. Aphakic eyes and looped IOLs developed Soemmering's
      rings peripherally. In eyes with small FSLs, PCO developed between the lens and
      the center of the posterior capsule, whereas in eyes with large FSLs, only small
      amounts of central PCO developed. Retained high-viscosity viscoelastic material
      had no effect on PCO development. CONCLUSIONS: Complete refilling of the capsular
      bag by a full-size IOL was associated with excellent centration and only a small
      degree of PCO. Elastic lenses may thus serve as a starting point for the
      development of an artificial lens with accommodative function.

PMID- 10079440
TI  - Intraocular recombinant tissue-plasminogen activator fibrinolysis of fibrin
      formation after cataract surgery in children.
AB  - PURPOSE: To evaluate the efficacy and safety of intracameral recombinant tissue
      plasminogen activator (rt-PA) application for fibrinolysis of fibrin formation
      after cataract surgery in children. SETTING: Johann Wolfgang Goethe-University,
      Department of Ophthalmology, Frankfurt am Main, Germany. METHODS: This study
      comprised 11 eyes of 10 patients aged 3 to 13 years (mean 7.2 +/- 3.68 [SD]) who
      developed severe fibrin formation after cataract surgery and IOL implantation
      despite intensive topical steroid therapy. Under general anesthesia, fibrinolysis
      was performed with 10 micrograms of rt-PA 7.18 +/- 2.04 days after intraocular
      surgery. Follow-up included slitlamp examination, tonometry, visual acuity
      testing, and-ophthalmoscopy. Anterior chamber flare measurements could be
      performed in 6 eyes. RESULTS: Complete resolution of fibrin formations occurred
      in 90% of the patients in these cases, no recurrent fibrinous reaction or adverse
      effects were noted. In 2 eyes of the same patient with a history of juvenile
      rheumatoid arthritis and chronic uveitis, fibrin clot dissolution was incomplete.
      A recurrent fibrinous formation could be observed after 2 and 4 weeks,
      respectively. A beginning band keratopathy excluding the central and limbal
      cornea was noted after 6 and 8 weeks, respectively. CONCLUSION: Intraocular
      application of rt-PA appears to be a safe and efficacious therapeutic approach in
      the management of severe fibrinous reactions after pediatric cataract surgery.

PMID- 10079441
TI  - Three-dimensional appearance of Bowman's layer after radial keratotomy.
AB  - PURPOSE: To examine the 3-dimensional collagen fibrillar architecture of Bowman's
      layer after radial keratotomy (RK). SETTING: Department of Ophthalmology, Niigata
      University School of Medicine, Niigata, Japan. METHODS: This study used monkey
      eyes in which 0.3 mm deep radial incisions were made on the cornea 2 weeks and 1,
      6, and 12 months before the animals were killed. Corneal buttons were immersed in
      a fixative and the cells macerated with sodium hydroxide 10%. Scanning electron
      microscopy (SEM) was performed according to standard procedures. A part of the
      specimens was embedded in epoxy resin for light microscopic (LM) observation for
      comparison. RESULTS: The 3-dimensional collagen fibrillar architecture of
      Bowman's layer was revealed by SEM. The rupture of Bowman's layer could be seen
      12 months after surgery and there was no continuity of collagen fibrils in the
      ruptured area. In LM observations, the width of the stromal incisions gradually
      became narrower near 12 months after surgery. CONCLUSION: Our cell-maceration/SEM
      method showed that the rupture of Bowman's layer remained up to 12 months after
      RK. This suggests that discontinuity of Bowman's layer may be responsible for
      globe rupture after RK.

PMID- 10079442
TI  - Change in corneal sensitivity following laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the change in corneal sensitivity following laser in situ
      keratomileusis (LASIK). SETTING: Department of Ophthalmology, Maryknoll Hospital,
      Pusan, Korea. METHODS: The corneal sensitivity in 40 eyes (32 patients) was
      measured before and 1 and 2 weeks and 1, 3, and 6 months after LASIK. Sensitivity
      measurements were made with an esthesiometer at central, temporal, inferior,
      nasal, and superior points on the corneal flap. The eyes were grouped by ablation
      depth: Group 1, corneal ablation depth less than 100 microns; Group 2, corneal
      ablation depth more than 100 microns. RESULTS: Corneal sensitivity did not
      recover to the preoperative level by 6 months after LASIK. Except at the hinge of
      the corneal flap, the pattern of sensitivity recovery was similar among the
      various points. Recovery was more rapid at the hinge than at other areas (P <
      .05). There was a trend toward a greater reduction in corneal sensitivity in
      Group 2, the group with deeper ablations, than in Group 1. CONCLUSION: The
      results suggest that lamellar cutting of the cornea during LASIK impairs corneal
      sensitivity and that the depth of the corneal ablation affects the extent of
      corneal sensitivity loss and recovery.

PMID- 10079443
TI  - Laser in situ keratomileusis versus arcuate keratotomy to treat astigmatism.
AB  - PURPOSE: To analyze the effectiveness of laser in situ keratomileusis (LASIK) and
      arcuate keratotomy (AK) to treat simple myopic, compound myopic, and mixed
      astigmatism. SETTING: Instituto de la Vision, Buenos Aires, Argentina. METHODS:
      This retrospective nonrandomized study comprised 821 cases treated with LASIK and
      46 cases treated with AK. Patients were divided into 4 groups, which had the
      following preoperative cylinder corrections: simple myopic astigmatism (Group 1)
      (LASIK: n = 76, -3.91 diopters [D] +/- 1.29 [SD]; AK: n = 5, -3.85 +/- 0.65 D);
      compound myopic astigmatism up to 2.00 D (Group 2) (LASIK: n = 401, -1.69 +/-
      0.76 D; AK: n = 14, -1.48 +/- 0.41 D); compound myopic astigmatism over 2.00 D
      (Group 3) (LASIK: n = 253, -3.61 +/- 0.89 D; AK: n = 16, -3.09 +/- 0.84 D); mixed
      astigmatism (Group 4) (LASIK: n = 91, +3.65 +/- 1.62 D; AK: n = 11, 4.39 +/- 0.92
      D). RESULTS: Six months postoperatively, the cylinder's vector-corrected change
      was as follows: Group 1, LASIK 3.75 +/- 1.08 D, AK 3.16 +/- 0.84 D; Group 2,
      LASIK 1.55 +/- 1.12 D, AK 1.34 +/- 0.44 D; Group 3, LASIK 3.39 +/- 0.98 D, AK
      2.70 +/- 1.21 D; Group 4, LASIK 3.77 +/- 1.43 D, AK 3.75 +/- 0.89 D. Respective
      mean uncorrected visual acuities in each group were as follows: Group 1, 0.71 +/-
      0.12 and 0.60 +/- 0.12; Group 2, 0.83 +/- 0.12 and 0.78 +/- 0.24; Group 3, 0.78
      +/- 0.18 and 0.48 +/- 0.24; Group 4, 0.69 +/- 0.21 and 0.55 +/- 0.18.
      CONCLUSIONS: The vector-corrected change and visual acuity achieved with LASIK
      were better, although not significantly, than those attained with AK except for
      the UCVA obtained with LASIK in eyes with compound myopic astigmatism over 2.00
      D. Both methods proved to be safe.

PMID- 10079444
TI  - Secondary laser in situ keratomileusis 1 year after primary LASIK for high
      myopia.
AB  - PURPOSE: To report the results of the laser in situ keratomileusis (LASIK) using
      a second-cut hinged corneal flap to treat regression 1 year after primary LASIK
      for high myopia. SETTING: Istanbul University, Eye Research Center, Istanbul,
      Turkey. METHODS: Six eyes of 4 patients who had a mean myopic regression of -6.20
      diopters (D) +/- 1.10 (SD) 1 year after primary LASIK were retreated with
      secondary LASIK performed using the Automated Corneal Shaper (Chiron Vision) and
      a 193 nm excimer laser (Chiron Technolas, Keracor 116). Fluence was 130 mJ/cm2
      and the repetition rate, 10 Hz. RESULTS: Mean follow-up was 12.16 +/- 0.75
      months. At the last follow-up, the mean spherical equivalent was -0.18 +/- 0.77 D
      (range +0.12 to -1.25 D). Two eyes (33.3%) remained within +/- 0.50 D of
      emmetropia; 5 eyes (83.3%) were within +/- 1.00 D of emmetropia. No patient lost
      best spectacle-corrected visual acuity. No complications occurred such as
      detachment of the former corneal flap and rolling, irregularity, or tearing of
      the new corneal flap. CONCLUSION: Secondary LASIK was an effective, safe method
      to treat regression after primary LASIK for high myopia.

PMID- 10079445
TI  - Surgically induced astigmatism after photorefractive keratectomy and laser in
      situ keratomileusis. Summit PRK-LASIK Study Group.
AB  - PURPOSE: To compare the axis and magnitude of surgically induced astigmatism in
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).
      SETTING: Multicenter clinical trial. METHODS: In this prospective randomized
      trial, 220 eyes of 220 patients entered the study cohort: 105 randomized to PRK
      and 115 to LASIK. All patients received a single-pass, multizone excimer laser
      ablation as part of a PRK or LASIK procedure. Attempted corrections ranged from 
      6.00 to -15.00 diopters (D). The LASIK procedures were performed with nasal
      hinges. Absolute changes in astigmatism and axis and magnitude of surgically
      induced astigmatism were analyzed. Patients were followed for up to 6 month.
      RESULTS: In the PRK group, the mean change in absolute astigmatism was +0.14,
      +0.16 and +0.32 D at 1, 3, and 6 months, respectively; in the LASIK group, the
      mean change was -0.15, -0.08, and -0.03 D, respectively. At all time points, a
      greater proportion of PRK than LASIK eyes had an increase in absolute magnitude
      of astigmatism. In the PRK group, the axis of vectoral-induced astigmatism was
      significantly different from random at 3 and 6 months (P = .01, P < .001),
      respectively) with a tendency for induced with-the-rule shifts postoperatively.
      In the LASIK group, the axis of vectoral-induced astigmatism was significantly
      different from random at only 1 month (P = .04), and there was no preponderant
      direction of axis shift. Despite these findings, other analyses showed no
      statistically significant between-group differences in vectoral axis or magnitude
      of surgically induced astigmatism. CONCLUSIONS: Induced astigmatism was generally
      less and more random in axis in LASIK than in PRK; a general trend for induced
      with-the-rule astigmatism in PRK was not seen in LASIK. Hypothetically, the
      lamellar corneal flap in LASIK may counteract the tendency toward steepening at
      90 degrees seen in PRK by retracting toward the hinge, by masking underlying
      induced astigmatism in the ablation zone, or by its mitigating influence on
      postoperative corneal healing.

PMID- 10079446
TI  - Binocular function after bilateral implantation of monofocal and refractive
      multifocal intraocular lenses.
AB  - PURPOSE: To evaluate binocular function after bilateral implantation of a
      refractive multifocal intraocular lens (IOL). METHODS: Contrast sensitivity,
      glare, depth discrimination, and distance and near visual acuity were examined in
      21 patients with a multifocal IOL and 15 patients with a monofocal IOL. RESULTS:
      There was no significant difference in binocular distance visual acuity between
      the 2 groups. In near visual acuity with distance correction, the multifocal
      group had a significant advantage in monocular and binocular vision (P < .05).
      High contrast with Regan contrast letter acuity charts did not differ
      significantly between the groups. However, at a contrast of 11%, sensitivity was
      significantly lower monocularly in the multifocal group. Contrast sensitivity in
      this group was not significantly lower binocularly. The brightness acuity tester
      revealed no between-group difference in glare. With the Titmus stereotest, depth
      discrimination was significantly better with the multifocal IOL with distance
      correction. CONCLUSION: Bilateral implantation of a refractive multifocal IOL
      provided good binocular function and alleviated the well-known disadvantage of
      reduced contrast sensitivity at low contrast levels.

PMID- 10079447
TI  - Comparison of the effectiveness of 4 anti-inflammatory drops in relieving
      photophobia after pupil dilation.
AB  - PURPOSE: To compare the relative effectiveness of diclofenac, flurbiprofen,
      ketorolac, and prednisolone acetate in relieving photophobia after pupil dilation
      for fundus examination. SETTING: Eye, Ear, Nose, and Throat Hospital, New
      Orleans, Louisiana, USA. METHODS: This prospective, blind, placebo-controlled
      study comprised 105 patients randomly assigned to 1 of 10 treatment groups. Five
      minutes after instillation of dilating drops, each patient received drops of
      different test medications in the right and left eyes. Light sensitivity and
      pupil measurement tests were performed over 2 hours after the pharmacological
      mydriasis. After photostimulation, patients were asked to rate their
      photosensitivity on numerical and analog scales and to indicate a filter value
      required to alleviate right-induced discomfort. Test results were analyzed to
      detect differences among the pain levels associated with each treatment. RESULTS:
      There were no significant differences between the placebo and any active
      treatment drug at any time during the study. CONCLUSION: These findings suggest
      that mediators other than prostaglandins may have a role in photosensitivity or
      that increased postmydriatic photosensitivity is a result of higher light levels
      entering the eye through the dilated pupil.

PMID- 10079448
TI  - Computerized method to measure glare and contrast sensitivity in cataract
      patients.
AB  - PURPOSE: To evaluate computerized methods for measuring glare sensitivity and
      visual acuity at 3 contrast levels in cataract patients. SETTING: St. Erik's Eye
      Hospital, Stockholm, Sweden. METHODS: In a prospective study, 25 consecutive
      cataract patients meeting the inclusion criteria were examined before and 12
      weeks after cataract surgery. Measured were glare sensitivity and visual acuity
      at 3 contrast levels using the Opthimus Y-VA Contrast Sensitivity Test and Glare
      Test. RESULTS: Preoperatively, all patients had impaired values compared with
      those in a group of age-matched normal volunteers (control group).
      Postoperatively, median values were similar to those in the age-matched control
      group in all parameters except glare sensitivity, which was significantly higher
      in the pseudophakic group (P = .03). Correlation coefficients between
      preoperative visual acuity and contrast sensitivity at 90%, 25%, and 10% were
      0.50 (P = .01), 0.53 (P = .006), and 0.45 (P = .02), respectively, and between
      preoperative visual acuity and preoperative glare difference, 0.45 (P = .02). A
      significant correlation was found between age and visual acuity in the control
      group at all contrast levels: 90% (r = 0.61, P = .0018), 25% (r = 0.52, P = .01),
      and 10% (r = 0.42, P = .04). Median differences between Y-VA examinations
      (repeatability) were 0 LogMAR except between examinations 1 and 2 at the 25%
      contrast level, where it was 0.3 LogMAR. CONCLUSION: The Ophthimus Y-VA Test and
      Glare Test were useful in the preoperative evaluation of patients with cataract
      and mild to moderate visual impairment.

PMID- 10079449
TI  - Effect of capsulorhexis size on postoperative intraocular pressure.
AB  - OBJECTIVE: To determine whether capsulorhexis diameter has an effect on
      intraocular pressure (IOP) after phacoemulsification. SETTING: SSK Ankara Eye
      Hospital, Ankara, Turkey. METHODS: This prospective study comprised 58 patients
      selected for cataract extraction by phacoemulsification using a 5.2 mm temporal,
      clear corneal incision. Twenty-nine of 58 patients had a 4.0 mm capsulorhexis and
      the rest, 6.0 mm. All patients received a multipiece poly(methyl methacrylate)
      posterior chamber intraocular lens with a 5.0 mm diameter bioconvex optic and
      flexible haptics. Follow-up was 3 months. Postoperative IOP was obtained by
      Goldmann applanation tonometry 1 and 2 days before surgery and 1 and 7 days and
      1, 2, and 3 months postoperatively. RESULTS: A significant decrease in IOP was
      observed in both the 4.0 and 6.0 mm capsulorhexis groups 1 day postoperatively (P
      < .0001 and P < .0001, respectively). At 3 months postoperatively, IOP decreased
      significantly over preoperative values both in the 4.0 mm (P < .0001) and 6.0 mm
      capsulorhexis (P = .0014) groups. There was a statistical difference between the
      mean 1 month IOP values in the 4.0 mm (11.34 +/- 2.18 mm Hg [SD]) and 6.0 mm
      capsulorhexis (13.00 +/- 2.30 mm Hg) groups (P = .0059). A statistical difference
      between the groups also existed at 3 months postoperatively (P = .0028).
      CONCLUSION: A 4.0 mm capsulorhexis resulted in lower postoperative IOP than a 6.0
      mm capsulorhexis 1 month postoperatively.

PMID- 10079450
TI  - Ab externo 4-point scleral fixation of posterior chamber intraocular lenses.
AB  - PURPOSE: To evaluate the results of ab externo 4-point scleral fixation of
      posterior chamber intraocular lenses (PC IOLs) as a primary or secondary
      procedure. SETTING: Aravind Eye Hospital, Madurai, India. METHODS: This
      retrospective study comprised 25 patients: 17 aphakic and 8 with traumatic
      subluxated lenses. The subluxated cataracts were removed intracapsularly. All
      patients had ab externo 4-point flapless scleral fixation of a PC IOL.
      Preoperative status, intraoperative details, and postoperative outcome were
      analyzed. RESULTS: Mean follow-up was 8.02 months (range 6 to 26 months). The
      preoperative findings included sector iridectomy (n = 6), peripheral anterior
      synechias (n = 5), corneal scar (n = 2), vitreous hemorrhage (n = 2), traumatic
      angle recession (n = 1), retinitis pigmentosa (n = 1), primary open-angle
      glaucoma (n = 1), and macular pigmentary mottling (n = 1). There were no
      intraoperative problems related to scleral fixation. Postoperative complications
      and findings included cystoid macular edema (CME) (n = 2), uveitis (n = 1), and a
      healed macular choroidal tear (n = 1). No patient had suture exposure, IOL
      tilt/decentration, or infection. Twenty-two patients (88.0%) had a visual acuity
      of 6/12 or better at final follow-up. The cause of poor visual recovery in 3
      patients included pre-existing macular degeneration, healed macular choroidal
      tear, and CME in 1 patient each. CONCLUSION: Four-point scleral fixation is a
      simple technique that in this series of 25 patients was not associated with major
      intraoperative or postoperative complications and gave satisfactory visual
      results.

PMID- 10079451
TI  - Corneal astigmatism after cataract surgery with 4.1 mm BENT scleral and 4.1 mm
      plus meridian corneal incisions.
AB  - PURPOSE: To determine whether the 4.1 mm BENT (between 9 and 12 o'clock) scleral
      incision or the 4.1 mm plus meridian corneal incision (PMCI) is better at
      minimizing postoperative astigmatism. SETTING: Department of Ophthalmology, Kobe
      City General Hospital, Kobe, Japan. METHODS: This prospective study comprised 58
      eyes of 29 consecutive patients with bilateral cataract. One eye was randomly
      assigned to have cataract surgery with a 4.1 mm BENT scleral incision and the
      other eye, with a 4.1 mm PMCI. Corneal astigmatism was measured before surgery
      and 1, 3, 10, 30, and 100 days after surgery. RESULTS: Mean astigmatism
      preoperatively and on postoperative days 1, 3, 10, 30, and 100 in the BENT
      scleral incision group was 0.99 +/- 0.66, 1.53 +/- 1.11, 1.12 +/- 0.72, 1.26 +/-
      0.81, 1.16 +/- 0.73, and 1.09 +/- 0.64 diopters (D), respectively. Means in the
      PMCI group were 1.14 +/- 0.79, 1.38 +/- 0.98, 1.17 +/- 0.88, 1.31 +/- 0.77, 1.01
      +/- 0.70, and 1.00 +/- 0.60 D. respectively. Astigmatism on days 1 and 10
      postoperatively was significantly greater than preoperatively in the BENT group
      (P < .03) but not in the PMCI group. The changes in astigmatism were less in the
      PMCI group at every examination and were significantly different 30 days
      postoperatively (P < .05). The negative correlation between preoperative
      astigmatism and the final postoperative change was significant in both groups (P
      < .032); the value of x-intercept of the regression line was 1.37 D in the BENT
      scleral incision group and 0.82 D in the PMCI group. CONCLUSION: In cataract
      surgery using a 4.1 mm incision, the PMCI surpassed the BENT scleral incision in
      minimizing postoperative corneal astigmatism.

PMID- 10079452
TI  - Converting to topical anesthesia in cataract surgery.
AB  - PURPOSE: To evaluate the complications and difficulties encountered by surgeons
      converting from paraocular to topical anesthesia in cataract surgery and to
      evaluate patient pain and satisfaction with each procedure. SETTING: Department
      of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland.
      METHODS: Three hundred eyes of 245 consecutive patients were prospectively
      assigned by permuted block-restricted randomization to receive topical
      (bupivacaine 0.75%) (Group 1; n = 136) or paraocular (Group 2; n = 163)
      anesthesia. The intraoperative conditions were judged by the surgeon. A numerical
      scale (0 to 10) was used to assess the degree of pain during administration of
      anesthesia, during surgery, and 1 and 24 hours postoperatively. Outcome measures
      were the number of complications and adverse events registered perioperatively
      and 4 months postoperatively as well as Snellen visual acuity and surgically
      induced astigmatism (SIA) measured 1 week and 4 months after surgery. RESULTS:
      The success of posterior chamber intraocular lens (IOL) implantation through a
      self-sealing clear corneal incision was very high (99.3% and 96.9% in Groups 1
      and 2, respectively). One case (0.7%) in the topical group required vitrectomy
      and implantation of an anterior chamber IOL. Anesthesia-related difficulties were
      reported in about 40% of patients in Group 1 and 4% in Group 2 (P < .001).
      Supplemental paraocular anesthesia was required in 4 cases (2.9%) in the topical
      group. Sedative/analgesic medication given perioperatively was required
      significantly more often in Group 1 (13.2%) than in Group 2 (2.4%) (P < .01).
      Significantly more pain during surgery (P < .001) and 1 hour after surgery (P <
      .001) was reported in the topical group. In Group 1 69.9% and in Group 2 93.3%
      reported no pain during surgery (P < .001). Chemosis (1.8%), subconjunctival
      hemorrhage (1.2%), and periorbital hematoma (1.2%) were seen only in the
      paraocular group. Perioperatively, no severe complications occurred in Group 1
      and the number of adverse events was less than in Group 2. Postoperatively, 2
      cases of endophthalmitis developed in the topical group and none in the
      paraocular group. There was no between-group difference in outcome measures; a
      visual acuity of 20/40 or better was found in 87.8% of eyes in Group 1 and 84.9%
      in Group 2 4 months postoperatively, and the percentages of eyes with SIAs within
      1.0 diopter of preoperative values were similar (78.6% and 73.3%, respectively).
      Patient preference for topical anesthesia appeared to be higher than for
      paraocular anesthesia. CONCLUSION: Paraocular anesthesia gave better analgesia
      than topical, but topical anesthesia provided acceptable analgesia during surgery
      and showed that intraocular procedures can be performed without akinesia. The
      surgeon converting to topical anesthesia may expect slight difficulty in 40% of
      cases and more severe difficulty in 7%. Surgically related complications were
      similar with both methods.

PMID- 10079453
TI  - Fresnel prism treatment of sensory exotropia with restoration of sensory and
      motor fusion.
AB  - Anterior segment surgeons may treat patients with long-standing media opacities
      or uncorrected aphakia who have developed sensory strabismus. These patients are
      at risk for diplopia after surgery to clear the visual axis and restore
      emmetropia. This report describes 2 patients who regained comfortable single
      binocular vision without strabismus surgery. Sensory fusion was restored with
      Fresnel prisms, which were weaned and ultimately discarded as the patients' motor
      fusion was re-engaged after decades of disuse. Surgeons who restore vision in an
      eye with manifest sensory strabismus should be aware of this noninvasive, well
      tolerated treatment option. Collaboration with an orthoptist or strabismologist
      may be helpful.

PMID- 10079454
TI  - Sight-threatening acute orbital swelling from peribulbar local anesthesia.
AB  - Severe allergic reactions to peribulbar local anesthesia are extremely rare. A 70
      year-old woman presented with acute orbital swelling and optic nerve dysfunction
      after a peribulbar local anesthetic injection. The patient was treated with acute
      orbital decompression as well as intravenous antibiotics and methylprednisolone;
      she made a good recovery. An allergy, probably to lignocaine, was the most likely
      cause. Urgent recognition and treatment of this condition may prevent potentially
      serious visual consequences.

PMID- 10079455
TI  - Managing a dropped nucleus during the phacoemulsification learning curve.
AB  - Three patients had a pars plana vitrectomy to remove retained nuclei within 72
      hours after phacoemulsification performed by a surgeon making the transition from
      extra-capsular cataract extraction to phacoemulsification. After vitrectomy, the
      nuclei were brought to the midvitreous cavity from the retinal surface with a
      posterior segment phacofragmenter, emulsified, and completely removed. Then, a
      posterior chamber intraocular lens was implanted in the sulcus through the
      previous cataract surgery incision and remained well centered postoperatively.
      Postoperative complications included cystoid macular edema in 1 patient and
      choroidal detachment in another. No other complications were detected. Final
      visual acuity ranged from 20/60 to 20/30.

PMID- 10079456
TI  - Progressive brown discoloration of silicone intraocular lenses after vitrectomy
      in a patient on amiodarone.
AB  - A patient who was treated with amiodarone for 3 years developed brown
      discoloration of the intraocular lenses in both eyes. Contrast sensitivity and
      blue perception were reduced in the right eye. After vitrectomy for a
      vitreoretinal traction syndrome in the left eye, the discoloration appeared to
      increase. The apparent progression may have been related to breakdown of the
      blood-aqueous barrier after vitrectomy. However, because the discoloration
      developed before surgery and was bilateral, long-term administration of
      amiodarone may also have played a role.

PMID- 10079457
TI  - Report of the Psychotherapy Task Force of the American Academy of Child and
      Adolescent Psychiatry.
AB  - In this task force report, the authors define the field of child and adolescent
      psychotherapy; review the state of the field with respect to advocacy, training,
      research, and clinical practice; and recommend steps to ensure that psychotherapy
      remains a core competence of child and adolescent psychiatrists.

PMID- 10079458
TI  - Some neurobiological aspects of psychotherapy. A review.
AB  - Ever since the idea was accepted that memory is associated with alterations in
      synaptic strength, studies on the cellular and molecular mechanisms responsible
      for the plastic changes in neurons have attracted wide interest in the scientific
      community. This article explores the process of memory consolidation leading to
      persistent modifications in synaptic plasticity as a mechanism by which
      psychotherapy facilitates changes in the permanent storage of information
      acquired throughout the individual's life. The psychobiological
      interrelationships of affect, attachment, and memory offer a perspective
      regarding the etiology and treatment of clinical disturbances of affect.
      Analogies between brain physiology and modes of psychotherapy provide the
      foundation for a review of psychiatric disorders involving the inability to
      control fear, obsessions, compulsions, and delusions, all of which respond to
      psychotherapeutic interventions.

PMID- 10079459
TI  - Empirical comparison of two psychological therapies. Self psychology and
      cognitive orientation in the treatment of anorexia and bulimia.
AB  - The authors investigated the applicability of self psychological treatment (SPT)
      and cognitive orientation treatment (COT) to the treatment of anorexia and
      bulimia. Thirty-three patients participated in this study. The bulimic patients
      (n = 25) were randomly assigned either to SPT, COT, or control/nutritional
      counseling only (C/NC). The anorexic patients (n = 8) were randomly assigned to
      either SPT or COT. Patients were administered a battery of outcome measures
      assessing eating disorders symptomatology, attitudes toward food, self structure,
      and general psychiatric symptoms. After SPT, significant improvement was
      observed. After COT, slight but nonsignificant improvement was observed. After
      C/NC, almost no changes could be detected.

PMID- 10079460
TI  - The broken mirror. A self psychological treatment perspective for relationship
      violence.
AB  - Clinicians face formidable challenges in working with male perpetrators of
      domestic violence. Many treatment programs use a confrontational approach that
      emphasizes male entitlement and patriarchal societal attitudes, without honoring
      the genuine psychological pain of the abusive male. Although some men with strong
      psychopathic tendencies are almost impossible to treat, the majority of spouse
      abusing males respond best to an empathic, client-centered, self psychological
      approach that also includes education about sociocultural issues and specific
      skill building. Understanding the deprivations in mirroring selfobject functions
      from which these men typically suffer facilitates clinical treatment response.
      While insisting that men take full responsibility for their abusive behavior,
      treatment approaches can still be most effective by addressing inherent
      psychological issues. Group leaders who can offer respect for perpetrators'
      history, their experience of powerlessness, and their emotional injuries in
      primary relationships are more likely to make an impact.

PMID- 10079461
TI  - Measuring therapist technique in psychodynamic psychotherapies. Development and
      use of a new scale.
AB  - Treatment manuals are becoming a requirement for conducting quality psychotherapy
      research. What the field lacks, however, are reliable, valid, and cost-efficient
      instruments that can be used to measure a wide variety of prescribed therapeutic
      techniques. This article describes the development and use of a new instrument,
      the Interpretive and Supportive Technique Scale (ISTS). It is designed to measure
      interpretive and supportive features of technique for a broad range of
      dynamically oriented psychotherapies. Data concerning the psychometric properties
      of the ISTS are presented from two studies. The findings suggest that the ISTS is
      a potentially useful tool for measuring interventions for different forms of
      dynamically oriented psychotherapy.

PMID- 10079462
TI  - Projective identification, countertransference, and the struggle for
      understanding over acting out.
AB  - Projective identification is examined as an intrapsychic and interpersonal
      phenomenon that draws the analyst into various forms of acting out. The therapist
      struggles to use understanding and interpretation as the method of working
      through the mutual desire to act out the patient's core fantasies and feelings.
      Clinical material is used to illustrate the ways in which projective
      identification affects the analytic relationship. The focus is on methods of
      using interpretation to shift from mutual acting out to mutual understanding.

PMID- 10079463
TI  - Should clinical training in long-term psychodynamic psychotherapy be mandatory in
      residency training? A debate.

PMID- 10079464
TI  - Essential amino acid composition and biological quality of yambean, Sphenostylis
      stenocarpa (Hochst ex A. Rich) harms.
AB  - The essential amino acids and protein bioavailability of raw, roasted and pre
      soaked, pressure cooked yambean were evaluated. Roasting caused decrease of 8%
      while soaking with pressure cooking caused decrease of 15-39% in the lysine
      composition of yambean. Rats fed raw, unprocessed bean diet showed overt signs of
      diarrhoea, poor protein utilization and hence poor growth. Processing
      considerably improved all growth indices--food conversion efficiency, protein
      efficiency ratio, digestibility, biological value, net protein utilization,
      protein retention efficiency and net protein ratio.

PMID- 10079465
TI  - Digestibility index and factors affecting rate of starch digestion in vitro in
      conventional food preparation.
AB  - The rate of starch hydrolysis in ten cereal-based food preparations was studied
      using an in vitro dialysis system. The foods were incubated with human saliva and
      porcine pancreatin. The sugars released after 3 h digestion were expressed as
      digestibility index (DI), the percentage starch digested was determined and
      correlated with the degree of gelatinization (DG). Granule morphology was also
      investigated and related with starch availability for hydrolysis. Significant
      differences were observed in the in vitro starch digestibility of the 10 foods (P
      < 0.05). The DI ranged from 53 for chapathi to 78 for rice flakes. DI was
      inversely related to the protein (r = -0.79, P < 0.01), fat (r = -0.63, P < 0.05)
      and energy (r = -0.61, P < 0.01). Percent starch digested was inversely related
      to the insoluble (r = -0.49, P < 0.05) and total dietary fiber (r = -0.63, P <
      0.01) content of the foods. The SEM results provided a better understanding of
      granular morphology on cooking and the effect of protein on limiting DG. The
      results suggest that carbohydrate foods of potential use in the therapeutic diets
      may be identified by their in vitro digestion characteristics.

PMID- 10079466
TI  - ONS guidelines on office-based clinical trials.

PMID- 10079467
TI  - Complementary treatments highlighted at recent meeting.

PMID- 10079468
TI  - Chronic myelogenous leukemia: update on biology and treatment.
AB  - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows
      a characteristic clinical course in which a chronic phase of variable duration
      precedes an accelerated, and ultimately blastic, phase, which is generally fatal.
      This disorder results from a clonal expansion of transformed hematopoietic
      progenitor cells and includes myeloid, monocytic, erythroid, megakaryocytic, and
      lymphoid lineages. At the molecular level, CML is characterized by the bcr-abl
      fusion gene, which results from the reciprocal translocation t(9;22)(q34;q11),
      creating the Philadelphia (Ph) chromosome. Chronic myelogenous leukemia was the
      first human disease for which a specific karyotype abnormality was demonstrated
      and could be linked to pathogenetic events of leukemogenesis. The outlook for
      patients with CML has changed dramatically over the last decade. The median
      survival time of patients has doubled to 5 to 7 years, with up to 50% of patients
      alive at 5 years. This development is due to refinements in allogeneic stem-cell
      transplantation and growing expertise in the use of interferon-alfa (Intron A,
      Roferon-A), a biological agent that has been shown to suppress the leukemic clone
      and to prolong survival in patients with CML. This review provides a concise
      update of the biology of CML, as well as current therapeutic options and
      management strategies.

PMID- 10079469
TI  - Molecular staging of prostate cancer: dream or reality?
AB  - The reverse transcriptase-polymerase chain reaction (RT-PCR) assay is an
      extremely sensitive technique for the detection of circulating cells expressing
      prostate-specific antigen (PSA) in prostate cancer patients. This article reviews
      the literature on the use of this technique as a preoperative parameter to
      predict both extraprostatic disease and PSA recurrence after radical
      prostatectomy. Despite the relative consensus regarding the increase in RT-PCR
      positivity with tumor stage (i.e., clinically localized vs metastatic prostate
      cancer), the use of RT-PCR as a clinical staging modality is controversial. To
      date, more than 16 institutions have evaluated the RT-PCR test in prostate
      cancer. Of these institutions, only two have reported the utility of RT-PCR as a
      staging modality and three have reported the utility of the test in predicting
      PSA recurrence. Before further conclusions are drawn regarding the clinical
      utility of RT-PCR in prostate cancer patients and its routine use is advocated, a
      larger patient population needs to be studied and followed for longer periods.

PMID- 10079470
TI  - High-dose cytarabine produces high cure rate in some AML patients.

PMID- 10079471
TI  - Alternatives to oral opioids for cancer pain.
AB  - Although the optimal route of administration of opioids is by mouth, some
      patients may require alternative routes during the course of their illnesses for
      several reasons. These include bowel obstruction, severe emesis, or severe
      dysphagia. In these cases, the alternatives include the subcutaneous or rectal
      route. The transdermal route also provides a simple, comfortable method that
      produces stable blood drug concentrations. The high potency and lipid solubility
      of fentanyl make it suitable for this route of administration. Iontophoresis can
      provide a rapid drug delivery rate, but no clinical studies exist to document the
      long-term effectiveness of this method in controlling pain. The transmucosal
      route is recommended only for those opioids with high solubility, such as
      buprenorphine, the fentanyl series, and methadone. Oral transmucosal fentanyl
      (Actiq) provides a rapid onset of pain relief and is appropriate for treating
      episodes of breakthrough pain.

PMID- 10079472
TI  - Clinical trials referral resource. Clinical trials of MGI-114.

PMID- 10079473
TI  - Fatigue is strongest cancer-related side effect, survey shows.

PMID- 10079474
TI  - Treatment of estrogen deficiency symptoms in women surviving breast cancer. Part
      2: Hormone replacement therapy and breast cancer.
AB  - There are several million breast cancer survivors worldwide. In the United
      States, 180,000 women were diagnosed with breast cancer in 1997, and
      approximately 97,000 of these women have an extremely low chance of suffering a
      recurrence of their cancer. With an average age at diagnosis of 60 years and a 25
      year expected duration of survival, the current number of breast cancer survivors
      in the United States may approach 2.5 million women. Since breast cancer is now
      being detected at an earlier stage than previously and since adjuvant
      chemotherapy may cause ovarian failure, an increasing number of women are
      becoming postmenopausal at a younger age after breast cancer treatment. This
      conference was convened in September 1997 to consider how menopausal breast
      cancer survivors should be treated at the present time and what future studies
      are needed to develop improved therapeutic strategies. A total of 59 breast
      cancer experts and patient advocates participated. The proceedings of the
      conference will be published in six installments in successive issues of
      ONCOLOGY. The first part, published last month, defined the problem and explored
      its magnitude and ramifications for patient management. This second part focuses
      on the benefits and risks of hormone replacement therapy (HRT) in patients with
      breast cancer.

PMID- 10079475
TI  - What BMT nurses should know about insurance issues.

PMID- 10079476
TI  - A primer on BMT for new transplant nurses.

PMID- 10079477
TI  - A bridge between psychoanalytic worlds: a dialogue with Rudolf Ekstein. Interview
      by Daniel Benveniste.

PMID- 10079478
TI  - The fundamental rule of psychoanalysis.

PMID- 10079479
TI  - Psychoanalysis, romanticism, and the nature of aesthetic consciousness, with
      reflections on modernism and postmodernism.

PMID- 10079480
TI  - Symbolic enactments in countertransference.

PMID- 10079481
TI  - Casablanca, Humphrey Bogart, the Oedipus complex, and the American male.

PMID- 10079482
TI  - Exterminate all rational thought: David Cronenberg's filmic vision of William S.
      Burroughs's Naked Lunch.

PMID- 10079483
TI  - Early pregnancy screening for fetal abnormalities.

PMID- 10079484
TI  - The menstrual history: old limitations, new prospects.

PMID- 10079485
TI  - Fetal growth rate and adverse perinatal events.
AB  - OBJECTIVE: To study fetal weight gain and its association with adverse perinatal
      events in a serially scanned high-risk population. SUBJECTS AND METHODS: A total
      of 200 pregnant women considered at increased risk of uteroplacental
      insufficiency had a total of 1140 scans in the third trimester, with a median of
      six scans in each pregnancy. The average fetal growth rate was retrospectively
      calculated for the last 6 weeks to birth, and expressed as daily weight gain in
      grams per day. Adverse pregnancy outcome was defined as operative delivery for
      fetal distress, acidotic umbilical artery pH (< 7.15), or admission to the
      neonatal intensive care unit (NICU). RESULTS: Fetuses with normal outcome in this
      high-risk pregnancy population had an average antenatal growth rate of 24.2
      g/day. Compared to pregnancies with normal outcome, the growth rate was slower in
      those that required operative delivery for fetal distress (20.9 g/day, p < 0.05)
      and those that required admission to the NICU (20.3 g/day, p < 0.05). The growth
      rate in pregnancies resulting in acidotic umbilical artery pH also seemed lower,
      but this did not reach statistical significance. CONCLUSIONS: Impaired fetal
      weight gain prior to birth is associated with adverse perinatal events suggestive
      of growth failure.

PMID- 10079486
TI  - Individual growth patterns in the first trimester: evidence for difference in
      embryonic and fetal growth rates.
AB  - OBJECTIVE: To evaluate individual fetal growth during the first trimester in
      pregnancies resulting from spontaneous and in vitro fertilization (IVF). METHODS:
      The growth of 11 fetuses conceived by spontaneous fertilization (known dates of
      ovulation) in nine patients and 15 fetuses conceived by IVF in 12 patients were
      evaluated at weekly intervals from 6 weeks, menstrual age, to 14 weeks. Fetal
      length was determined at each examination. Measures of fetal length included the
      crown-rump length (CRL), maximum straight line length (MSLL) and maximum axial
      length (MAL). Comparisons of CRL and MSLL to MAL were carried out. The MSLL was
      used as the measure of length except when the MAL was available. Linear and
      quadratic functions were fitted to the complete data sets of individual fetuses
      in the two groups. Individual data sets from ten fetuses in each group were then
      divided into early and late growth phases, and linear functions were fitted to
      each data subset. Start points and pivotal points for each fetus were estimated
      from the coefficients of these two functions. Growth in these two groups of
      fetuses was compared, on the basis of slope values. RESULTS: Evaluation of length
      measures indicated that, before 8 weeks, only MSLL could be measured. After 8
      weeks, all three measures could be obtained, with the MAL being the largest. Both
      the linear and quadratic models performed well with individual data sets (mean
      R2(+/- SD): linear 98.1 (1.0)%; quadratic 99.4 (0.4)%), with no differences found
      between spontaneous and IVF groups (maximum possible differences in mean slopes
      (95% probability): 5-8%). Similar findings were obtained for the early and late
      growth phase data subsets. Slope values in the early and late growth phases
      showed low variability (CV: early 13.5%; late 11.6%), but were significantly
      different (early 0.72 (+/- 0.10 SD) cm/week; late 1.21 (+/- 0.14 SD) cm/week).
      The mean start point was 5.9 (+/- 0.3 SD) weeks' menstrual age, while the mean
      pivotal point was 9.2 (+/- 0.7 SD) weeks, menstrual age. CONCLUSIONS: First
      trimester growth studies in individual fetuses indicate that there is a change in
      length growth rate between 9 and 10 weeks, menstrual age. This is consistent with
      a shift in development from organogenesis to growth. These results can be used
      for more accurate assessment of first-trimester growth and may aid in the
      detection of fetal problems that manifest themselves as growth abnormalities.

PMID- 10079487
TI  - Accuracy of sonographic estimates of fetal weight in very small infants.
AB  - OBJECTIVE: Fetal outcome is inversely related to gestational age and birth
      weight. Therefore, in very small fetuses, estimated weight may play an important
      role in clinical management. Our aim was to determine the accuracy of sonographic
      estimates of fetal weight in very small infants. DESIGN: Retrospective chart
      review. SUBJECTS: We retrospectively studied 100 consecutive infants with a birth
      weight of < 1000 g, at a gestational age between 24.0 and 34.0 weeks, in which
      biometric data < 2 weeks prior to delivery were available for analysis. METHODS:
      We estimated fetal weight with the use of two methods--by those of Hadlock and
      colleagues and Scott and colleagues--and compared the estimated values with
      measured birth weights. RESULTS: The infants had a mean birth weight of 742 +/-
      173 (SD) g, at a gestational age of 28.1 +/- 2.0 (SD) weeks. With Hadlock's
      method, the mean estimated fetal weight (EFW) was 736 +/- 186 (SD) g, which was
      not significantly different from birth weight; the mean EFW error was 0.8 +/-
      12.7 (SD) %. With Scott's method, the mean EFW was 780 +/- 185 (SD) g, which was
      significantly increased above birth weight; the mean EFW error was 5.7 +/- 12.5
      (SD) %. The accuracy of the weight estimates was not significantly affected by
      the period between ultrasound examination and delivery if < 2 weeks, or by fetal
      growth restriction. CONCLUSION: In our population of small fetuses, Hadlock's
      estimates of fetal weight correlated well with measured birth weight, whereas
      Scott's method tended to overestimate.

PMID- 10079488
TI  - Clinical interpretation of ultrasound biometry for dating and for assessment of
      fetal growth using a wheel and chart: is it sufficiently accurate?
AB  - OBJECTIVES: To investigate how accurately practicing obstetricians (experts) can
      apply dating rules and compare the interpretation of gestation-sensitive
      ultrasound data with those of a computer system. SUBJECTS: Seventeen practicing
      obstetricians. Members of the Royal College of Obstetricians and Gynaecologists,
      from 14 different units throughout the UK. DESIGN: Six cases with menstrual and
      ultrasound data together with identical ultrasound charts and obstetric wheels.
      MAIN OUTCOME MEASURES: Concordance between the calculated estimated date of
      delivery (EDD) and growth assessment provided by the experts and the computer
      system. RESULTS: The calculation of the EDD by the experts was imprecise (59%
      within 3 days overall). Concordance with the computer calculation was poorest
      when the ultrasound measurements lay close to the upper or lower centile lines
      (average 7% within 3 days of the computer). Interpretation of growth showed good
      concordance with the computer when gestation was not critical to the
      interpretation (94%), but very poor when gestation was critical (7%).
      CONCLUSIONS: Calculation of EDD by means of an obstetric wheel and charts is not
      precise. Compared with the computer system, these errors have a significant
      effect on the subsequent interpretation of growth scans when the data are
      borderline. A computer system provides the more accurate method for interpreting
      gestation-sensitive ultrasound biometry.

PMID- 10079489
TI  - Can transvaginal fetal biometry be considered a useful tool for early detection
      of skeletal dysplasias in high-risk patients?
AB  - OBJECTIVE: To evaluate the possibility of an early diagnosis of skeletal
      dysplasias in high-risk patients. METHODS: A total of 149 consecutive,
      uncomplicated singleton pregnancies at 9-13 weeks' amenorrhea, with certain
      menstrual history and regular cycles, were investigated with transvaginal
      ultrasound to establish the relationship between femur length and menstrual age,
      biparietal diameter and crown-rump length, using a polynomial regression model. A
      further eight patients with previous skeletal dysplasias in a total of 13
      pregnancies were evaluated with serial examinations every 2 weeks from 10-11
      weeks. RESULTS: A significant correlation between femur length and crown-rump
      length and biparietal diameter was found, whereas none was observed between femur
      length and menstrual age. Of the five cases with skeletal dysplasias, only two
      (one with recurrent osteogenesis imperfecta and one with recurrent
      achondrogenesis) were diagnosed in the first trimester. CONCLUSIONS: An early
      evaluation of fetal morphology in conjunction with the use of biometric charts of
      femur length against crown-rump length and femur length against biparietal
      diameter may be crucial for early diagnosis of severe skeletal dysplasias. By
      contrast, in less severe cases, biometric evaluation appears to be of no value
      for diagnosis.

PMID- 10079490
TI  - The effects of maternal indomethacin therapy on human fetal branch pulmonary
      arterial vascular impedance.
AB  - OBJECTIVE: To examine whether maternal indomethacin therapy affects human fetal
      pulmonary arterial vascular impedance without constriction of the ductus
      arteriosus and to determine the changes in the pulmonary arterial vascular
      impedance in the presence of ductal constriction. STUDY DESIGN: In this cross
      sectional study, 52 normal fetuses without maternal medication (control group),
      33 fetuses without ductal constriction (Study group I) and 11 fetuses with ductal
      constriction (Study group II) during maternal indomethacin therapy between 24 and
      34 weeks of gestation were examined by Doppler echo-cardiography. Blood velocity
      waveforms across the proximal right or left pulmonary artery were obtained and
      the pulsatility index (PI) of the proximal pulmonary arteries was calculated.
      RESULTS: In the control group, the proximal pulmonary artery PI was higher (p <
      0.0001) at 24-25 weeks (n = 7) (3.73 +/- 0.33; mean +/- SD) than at 33-34 week of
      gestation (n = 11) (2.98 +/- 0.27). The PI was constantly greater (p < 0.005) in
      Study group I than in the control group. However, in this group the mean average
      weekly decrease in the PI of the proximal pulmonary arteries was similar to that
      in the control group. After 26 weeks of gestation, the PI values in Study group
      II were significantly higher than in the control group (27 weeks: 4.12 vs. 3.34
      (p < 0.005); 30 weeks: 4.48 vs. 3.14 (p < 0.0001); 34 weeks: 4.96 vs. 3.00 (p <
      0.0001), respectively). CONCLUSIONS: Human fetal pulmonary arterial vascular
      impedance is increased by maternal indomethacin therapy even without ductal
      constriction. In the presence of ductal constriction, the magnitude of the
      increase in the vascular impedance is related to the gestational age.

PMID- 10079491
TI  - Comparison of prenatal ultrasound and postmortem findings in fetuses and infants
      with congenital heart defects.
AB  - OBJECTIVE: Detection of congenital heart defects by prenatal ultrasound
      examination has been one of the great challenges since the investigation for
      fetal anomalies became part of the routine fetal examination. This prospective
      study was designed to evaluate the concordance of prenatal ultrasound findings
      with autopsy examination in a population consisting of both referred women and
      non-selected pregnant women. DESIGN: Criteria for inclusion were an ultrasound
      examination at the National Center for Fetal Medicine and an autopsy performed
      during the years 1985-94. Results from the ultrasound and autopsy examinations
      were systematized into categories depending on the degree of concordance.
      RESULTS: Of 408 infants and fetuses with developmental anomalies, 106 (26%) had
      congenital heart defects. In 63 (59%) of these 106 cases, the heart defect was
      the principal reason for the termination of pregnancy or the cause of death.
      Excluding five cases with a secundum atrial septal defect, there was complete
      agreement between the ultrasound examination and the autopsy findings in 74 (73%)
      of 101 cases. In 18 cases, there were minor discrepancies between ultrasound and
      autopsy findings. The main diagnosis was thus correct in 92 cases (91%). From the
      first time period (1985-89) to the second (1990-94), the detection rate of all
      heart defects increased from 48% to 82%. CONCLUSION: This study confirms a good
      correlation between ultrasound and autopsy diagnoses in fetuses and infants with
      congenital heart defects. A significant improvement in the detection of heart
      defects occurred from the first time period to the second and was probably due to
      increased experience and technical advances.

PMID- 10079492
TI  - Fetal yawning activity in normal and high-risk fetuses: a preliminary
      observation.
AB  - OBJECTIVE: To study yawning activity in healthy fetuses and in fetuses at high
      risk. METHODS: Yawning activity was studied in 16 healthy and 22 high-risk
      fetuses. Studies were performed in the postprandial state at 09.00 and 12.00 in a
      quiet room with the woman in the lateral recumbent position. All ultrasound
      examinations were performed using a 3.5-MHz Acuson 128 PX curvilinear probe.
      Fetal lips, mouth, tongue, pharynx, larynx, trachea and esophagus were surveyed
      in serial coronal and sagittal planes. All fetal mouthing movements were analyzed
      by a review of the videotape in slow motion. RESULTS: In both normal and high
      risk fetuses, yawning was represented by isolated mouthing movements and
      consisted of slow opening of the mouth with simultaneous downward movements of
      the tongue. This phase occupied 50-75% of the yawning cycle. After reaching its
      maximum opening, the mouth remained wide open for 2-8 s and returned to its
      resting position within seconds. Growth-restricted fetuses demonstrated yawning
      patterns consisting of isolated yawns similar to those seen in healthy fetuses.
      Unusual bursts of fetal yawning activity were recorded in anemic fetuses.
      CONCLUSION: Yawning activity in anemic fetuses may represent a compensatory
      process to increase venous return to the heart.

PMID- 10079493
TI  - The effectiveness of non-surgical management of early interstitial pregnancy: a
      report of ten cases and review of the literature.
AB  - OBJECTIVE: To assess the effectiveness of non-surgical management of interstitial
      pregnancy. DESIGN: A prospective interventional study. SUBJECTS: Eleven women
      with the ultrasound diagnosis of interstitial ectopic pregnancy. METHODS: Women
      with suspected early pregnancy complications were examined by transvaginal
      ultrasound. Those with the diagnosis of interstitial pregnancy were offered non
      surgical treatment with methotrexate, which was administered systemically or by
      local injection. Follow-up with regular measurements of beta-human chorionic
      gonadotropin and ultrasound scans continued until the pregnancy had resolved
      completely. RESULTS: Ten women were managed non-surgically, and one woman opted
      for surgery. Five women received systemic and five local methotrexate. Local
      therapy was successful in all five cases (100%), whereas four out of five (80%)
      women receiving systemic methotrexate were cured. Significant side-effects were
      noted in two women following systemic therapy. In comparison, there were no side
      effects in the group of women who received local therapy. There were no
      significant differences between the two treatment groups in the length of time
      taken for the pregnancy to resolve. CONCLUSIONS: Non-surgical treatment of
      interstitial pregnancy with methotrexate appears to be safe and effective. Local
      administration appears to be more successful and better tolerated by patients and
      may be used as the first-line therapy.

PMID- 10079494
TI  - Intravaginal saline as a contrast agent for cervical sonography in the obstetric
      patient.
AB  - OBJECTIVE: To determine whether intravaginal saline alters visualization of the
      cervix during endovaginal sonographic examinations. DESIGN: A prospective trial
      with comparison of sonographic measurements of cervical length prior to and after
      administration of an intravaginal contrast agent. SUBJECTS: Patients with an
      indication for endovaginal ultrasonographic assessment of the cervix were
      considered as candidates for the study. METHODS: After assessment of cervical
      dimensions and contour of the internal cervical os, 10 ml of normal saline was
      placed intravaginally via a needleless syringe. Pre- and post-contrast
      sonographic examinations of the cervix were compared. RESULTS: Twenty-six
      patients were enrolled. No differences were observed in the identification of
      funnelling (37% in each group, p = 1.0) or the quantification of cervical length
      for the entire cohort (p = 0.95). However, in a subset of patients in whom the
      external os was not satisfactorily visualized (23%), intravaginal contrast
      resulted in a mean difference in cervical length pre- and post-saline infusion of
      6.4 mm compared to 1.4 mm in patients in whom the external os could be easily
      identified (p < 0.001). No patient expressed undue discomfort related to the
      administration of contrast. CONCLUSION: Intravaginal saline assists in
      visualization of the cervix during endovaginal sonography for selected patients
      in whom precise identification of the external os is difficult.

PMID- 10079495
TI  - First-trimester cord entanglement in monoamniotic twins.
AB  - OBJECTIVE: Monoamniotic twinning occurs in only 1% of twin pregnancies, but
      carries a high perinatal mortality rate. Early and reliable diagnosis is
      essential if attempts are to be made to reduce the complication rate. We report
      color Doppler demonstration of cord entanglement in the first trimester, which is
      diagnostic of monoamnionicity. METHODS: Two patients with twin pregnancies were
      examined in the first trimester with pulsed and color Doppler insonation of their
      umbilical arteries. RESULTS: Cord entanglement was suspected and proved by
      demonstrating differing fetal heart rate patterns in the same direction on
      umbilical artery Doppler analysis of a common mass of cord vessels. Following
      appropriate counselling, medical amnioreduction was induced at 20 weeks of
      gestation to reduce fetal movements and worsening cord entanglement. Delivery was
      by elective Cesarean section at 32 weeks' gestation and monoamnionicity was
      confirmed. CONCLUSION: We report a new sign for the demonstration of
      monoamnionicity in twin pregnancies in the first trimester. This should improve
      the reliability of early diagnosis, but further studies are required to confirm
      that, if cord entanglement occurs, it is usually present by the end of the first
      trimester.

PMID- 10079496
TI  - Diagnosis of twin reversed arterial perfusion sequence in the first trimester by
      transvaginal color Doppler ultrasound.
AB  - A case of twin reversed arterial perfusion (TRAP) sequence was diagnosed at 12
      weeks' gestation using transvaginal color Doppler ultrasound, which demonstrated
      the presence of retrograde perfusion in the umbilical artery of the abnormal
      twin. Ultrasound imaging showed a monochorionic-diamniotic twin pregnancy with an
      inappropriately grown second twin, the morphological evaluation of which revealed
      an abnormal cephalic pole with acrania, diffuse subcutaneous edema and the
      presence of cardiac activity in an abnormal heart with a single chamber.

PMID- 10079497
TI  - Focal aneurysmal dilatation of subchorionic vessels simulating chorioangioma.
AB  - Subchorionic vascular aneurysms of the placenta are rare lesions and may present
      confusion with chorioangioma or focal mesenchymal dysplasia on sonography. To our
      knowledge, the findings of placental aneurysms have not been reported in the
      ultrasound literature. We present a case with detailed sonographic evaluation,
      including spectral and color Doppler and pathological analysis, that was mistaken
      for chorioangioma prenatally. Knowledge of this benign entity may allow the
      sonologist to recommend conservative management in similar cases.

PMID- 10079498
TI  - Micturition in utero.

PMID- 10079499
TI  - Stereospecific pharmacokinetics and toxicodynamics of ketorolac after oral
      administration of the racemate and optically pure enantiomers to the rat.
AB  - To determine the stereospecific pharmacokinetics and gastrointestinal
      permeability (GI) changes (surrogate measures of toxicity) in the rat following
      oral administration of S, R, and racemic ketorolac (KT), optically pure
      enantiomers (S and R 2.5 mg/kg), and racemic KT (5 mg/kg) were administered
      orally to male Sprague-Dawley rats and plasma samples were collected for 6 h post
      dose for pharmacokinetic assessments. KT-induced changes in GI permeability were
      assessed using sucrose and 51Cr-EDTA as markers of gastroduodenal and distal
      intestinal permeability, respectively. After the racemate, R-KT was predominant
      in plasma (AUC S/R, 0.45). No significant differences in pharmacokinetic indices
      were evident following administration of the racemate as compared with individual
      enantiomers. In plasma, there was only negligible S-KT after administration of R
      KT. After S-KT, on the other hand, AUC of R-KT was found to be 6.7% of that of S
      KT. Both permeability markers showed considerable interanimal variability.
      Gastroduodenal permeability was significantly increased from baseline by the
      racemate but not by either of the two enantiomers administered alone.
      Permeability to 51Cr-EDTA was not significantly increased above baseline for any
      of the treatments. The plasma concentration of R-KT found after administration of
      S-KT may be from the < 2% chiral impurity which appears magnified due to its
      slower clearance as compared with its antipode. There is no evidence of a
      pharmacokinetic interaction between the enantiomers. Since 2.5 mg/kg S-KT is
      somewhat less toxic on the gastroduodenum than 5 mg/kg racemate, it may be a
      safer alternative to the latter, at least in the rat model.

PMID- 10079500
TI  - Headspace gas chromatography-mass spectrometry analysis of isoflurane enantiomers
      in blood samples after anesthesia with the racemic mixture.
AB  - Several in vivo and in vitro studies on the stereoselective potency of isoflurane
      enantiomers suggest beneficial effects of the (+)-(S)-enantiomer. In order to
      detect possible differences in the pharmacokinetics of isoflurane enantiomers, a
      clinical study of 41 patients undergoing general anesthesia maintained with
      racemic isoflurane was performed. The isoflurane enantiomers were analyzed in
      blood samples drawn before induction, at cessation (day 0), and up to eight days
      after isoflurane anesthesia (day 1-8). A multipurpose sampler (Gerstel MPS) was
      used for the headspace gas chromatography-mass spectrometry (GC/MS) analysis, and
      it was combined with a cold injection system (Gerstel CIS 3) for coldtrapping,
      enrichment, and focusing of the analyte. The enantiomer separation was achieved
      by using a capillary column coated with octakis(3-O-butanoyl-2,6-di-O-pentyl)
      gamma-cyclodextrin (Lipodex E) dissolved in the polysiloxane PS 255. Detection
      was done in the selected ion monitoring mode with ions m/z 117 and m/z 149. An
      enrichment of (+)-(S)-isoflurane in all blood samples drawn after anesthesia was
      found. The highest enantiomer bias, up to 52-54% (+)-(S)-isoflurane as compared
      to 50% for the racemate, was observed on day 2 for most of the patients.
      Furthermore, quantification of isoflurane in blood samples of five patients was
      done by enantiomer labeling, employing enantiomerically pure (+)-(S)-isoflurane
      as internal standard. The isoflurane concentration decreased rapidly from 383
      nmol/ml to 0.6 nmol/ml (mean values) eight days after anesthesia. The present
      study shows differences in the pharmacokinetics of isoflurane enantiomers in man.
      However, it is not possible to distinguish between enantioselective distribution
      and enantioselective metabolism, if any.

PMID- 10079501
TI  - Enantioselective kinetic disposition of albendazole sulfoxide in patients with
      neurocysticercosis.
AB  - The enantioselectivity of the kinetic disposition of albendazole sulfoxide (ASOX)
      was investigated in 18 patients with neurocysticercosis treated with a multiple
      dose regimen of albendazole for 8 days (5 mg/kg every 8 h). Serial blood samples
      were collected on the eighth day of treatment during the last dose interval, with
      prorogation up to 12 h. Albendazole sulfone (ASON) and enantiomers of ASOX were
      analyzed in plasma samples by HPLC using a Chiralpak AD column and detection by
      fluorescence. The pharmacokinetic parameters showing statistically significant
      differences between the (+) ASOX and (-) ASOX enantiomers are presented as
      respective means (95% CI) as follows: maximum plasma concentration, Cmax = 301.6
      (179.7-423.5) vs 54.9 (21.9-87.9) ng.ml-1; elimination half-life, t1/2 = 5.2 (4.1
      6.3) vs 3.3 (2.8-3.8) h, area under the plasma concentration-time curve, AUCss0-8
      = 1719.2 (978.6-2459.8) vs 261.4 (102.9-419.8) ng.h.ml-1 and apparent clearance,
      Cl/fm = 5.8 (3.8-7.8) vs 54.0 (35.2-72.7) l.h-1.kg-1. The mean value of 9.2 (7.6
      10.9) for the AUC0-8(+)-ASOX/AUC0-8(-)-ASOX ratio demonstrated plasma
      accumulation of the (+) enantiomer. Sulfone formation capacity, expressed by the
      AUCss0-8 ratio ASON/ASOX + ASON, was 8.0 (7.0-8.9). The present data indicate
      enantioselectivity in the kinetic disposition of ASOX in patients with
      neurocysticercosis.

PMID- 10079502
TI  - Stereoselective metabolism of tazofelone, an anti-inflammatory bowel disease
      agent, in rats and dogs and in human liver microsomes.
AB  - Incubation of (R)-tazofelone and (S)-tazofelone in rat, dog, and human liver
      microsomes demonstrated that the (R)-tazofelone enantiomer was more rapidly
      metabolized, with two diastereomeric sulfoxides as the major metabolites formed
      in all three species. The two diasteresomers epimerized at physiological pH,
      therefore total sulfoxide formation rates were measured. The formation of the
      total sulfoxide metabolites followed Michaelis-Menten kinetics. The K(m), Vmax,
      and intrinsic formation clearance (Vmax/K(m)) values were determined in rat, dog,
      and human liver microsomes. The intrinsic formation clearance of sulfoxide from
      (R)-tazofelone exceeded that of (S)-tazofelone in all three species. In vivo
      studies in rats and dogs dosed orally and intravenously confirmed the
      stereoselective metabolism of tazofelone observed in vitro. Plasma concentrations
      of (S)-tazofelone exceeded (R)-tazofelone in rats and dogs by a factor of 3 to 4.
      In rat portal plasma, both enantiomers were of approximately equal concentration
      after oral dosing, indicating similar absorption. The half-lives of tazofelone
      and total sulfoxides in rats were 3.5 and 2.8 h, respectively. In dogs, the half
      lives of tazofelone and total sulfoxides were 2.2 and 5.5 h, respectively. Plasma
      clearance was 2.3 l/h in rats and 1.4 l/h in dogs, and the volumes of
      distribution were 12 and 4.5 l, respectively, in rats and dogs. Both enantiomers
      were highly bound to plasma proteins to a similar extent in both species.

PMID- 10079503
TI  - Convergent synthesis, chiral HPLC, and vitamin D receptor affinity of analogs of
      1,25-dihydroxycholecalciferol.
AB  - A series of analogs of 1,25-dihydroxycholecalciferol was obtained with an
      additional chiral center at the terminus of the aliphatic side chain (C-25). The
      analogs were obtained from (+)-(R)- and (-)-(S)-2-methylglycidols, by opening of
      the oxirane ring with the carbanions derived from vitamin D C23a,24- or C22
      sulfones. The diastereomeric purity of the analogs was determined by high
      performance liquid chromatography on a chiral stationary phase. The binding
      affinity of analogs for the calf thymus intracellular vitamin D receptor (VDR)
      was two orders of magnitude lower than that of the lead compound of this group,
      24a,24b-dihomo-1,25-dihydroxycholecalciferol, and it was comparable to the
      affinity of analogs of 24-nor-1,25-dihydroxycholecalciferol. However, a twofold
      difference was observed for analogs diastereomeric at C-25 in their affinity for
      VDR. The diastereodifferentiation of the binding affinity was found to be
      specific for vitamin D vicinal 25,26-diols as it disappears for analogs where 26
      hydroxyl, neighboring the C-25 chiral center, is replaced with methyl.

PMID- 10079504
TI  - Therapeutic agent for treating dysuria (NC-1800): absolute configuration of the
      enantiomers.
AB  - The absolute configuration of an enantiomer of the title compound, (+/-)-1.
      fumaric acid salt, was determined by X-ray crystallographic analysis of (+)-1
      [salt of (+)-tartaric acid [(+)-2]]. This salt for X-ray crystallographic
      analysis was prepared by a simple method. The analysis of (+)-1 [salt of (+)-2]
      showed that this enantiomer has the 5-S and 1-R absolute configuration. The final
      R and Rw values were 0.0614 and 0.0713, respectively.

PMID- 10079505
TI  - Genes, gene knockouts, and mutations in the analysis of gap junctions.
AB  - Gop junctions are cell junctions found between most cells and tissues. They
      contain membrane channels that mediate the cell-to-cell diffusion of ions,
      metabolites, and small cell signaling molecules. Cell-cell communication mediated
      by gap junctions has been proposed to have a variety of functions, including
      roles in regulating events in development, cell differentiation, and cell growth
      and proliferation. The analysis of these possibilities has been confounded by the
      fact that there are over a dozen connexin genes encoding polypeptides that make
      up vertebrate gap junctions. This complexity, coupled with the fact that most
      cells express multiple connexin isotypes, likely explains why recent studies
      using reverse genetic and genetic approaches to disrupt connexin gene function
      have yielded only limited insights into the physiological roles of gap junctions.
      Nevertheless, studies in vivo and in vitro together have provided evidence for
      gap junctions being involved in the regulation of cell metabolism, growth, and
      differentiation in restricted cell and tissue types. Surprisingly, studies in
      invertebrates suggest that their gap junctions are encoded not by connexins, but
      by a family of proteins referred to as innexins. Analysis of various Drosophila
      and C. elegans mutants suggest that innexins may be functional homologs to the
      connexins. However, whether innexins are the elusive invertebrate gap junction
      proteins or, rather, accessory proteins that facilitate gap junction formation
      remains an open question. Given the rapid progress being made in the cloning and
      functional analysis of gap junctions in many diverse species, confusion and
      difficulties with nomenclature are coming to a head in this rapidly expanding
      field. It may be timely to form a Nomenclature Committee to establish a uniform
      classification scheme for naming gap junction proteins.

PMID- 10079506
TI  - Doubly mutant mice, deficient in connexin32 and -43, show normal prenatal
      development of organs where the two gap junction proteins are expressed in the
      same cells.
AB  - The connexins are a family of proteins that form the intercellular membrane
      channels of gap junctions. Genes encoding 13 different rodent connexins have been
      cloned and characterized to date. Connexins vary both in their distribution among
      adult cell types and in the properties of the channels that they form. In order
      to explore the functional significance of connexin diversity, several mouse
      connexin-encoding genes have been disrupted by homologous recombination in
      embryonic stem cells. Although those experiments have illuminated specific
      physiological roles for individual connexins, the results have also raised the
      possibility that connexins may functionally compensate for one another in cells
      where they are coexpressed. In the present study, we have tested this hypothesis
      by interbreeding mice carrying null mutations in the genes (Gjb1 and Gja1)
      encoding connexin32 (beta 1 connexin) and connexin43 (alpha 1 connexin),
      respectively. We found that fetuses lacking both connexins survive to term but,
      as expected, the pups die soon thereafter from the cardiac abnormality caused by
      the absence of connexin43. A survey of the major organ systems of the doubly
      mutant fetuses, including the thyroid gland, developing teeth, and limbs where
      these two connexins are coexpressed, failed to reveal any morphological
      abnormalities not already seen in connexin43 deficient fetuses. Furthermore, the
      production of thyroxine by doubly mutant thyroids was confirmed by
      immunocytochemistry. We conclude that, at least as far as the prenatal period is
      concerned, the normal development of those three organs in fetuses lacking
      connexin43 cannot simply be explained by the additional presence of connexin32
      and vice-versa. Either gap junctional coupling is dispensable in embryonic and
      fetal cells in which these two connexins are coexpressed, or coupling is provided
      by yet another connexin when both are absent.

PMID- 10079507
TI  - Loss of alpha 1 connexin does not alter the prenatal differentiation of
      pancreatic beta cells and leads to the identification of another islet cell
      connexin.
AB  - Connexin alpha 1, also referred to as Cx43, has thus far been the only gap
      junction protein identified between the hormone-producing cells of pancreatic
      islets. To investigate whether loss of this connexin affects the development of
      endocrine pancreas and the differentiation of insulin-producing beta cells, we
      have taken advantage of a transgenic line in which the gene coding for connexin
      alpha 1 had been functionally deleted by homologous recombination. Analysis of
      pancreas at embryonal day 19.5 (E 19.5) after immunostaining for the four main
      types of islet hormones, showed that islet cell development was similar in
      homozygous transgenic mice that completely lacked alpha 1 connexin, in mice that
      were heterozygous for the transgene, and in age-matched controls with a genetic
      background similar to that of the transgenic animals. In particular, the three
      animal groups featured beta cells that had a similar insulin content and
      ultrastructural organization, including the presence of typical gap junction
      plaques on the membrane. However, quantitative analysis of freeze-fractured
      membranes showed that these plaques were less frequent in the transgenic mice
      lacking alpha 1 connexin. This finding prompted us to revisit the connexin
      pattern of normal pancreatic beta cells. Using RT-PCR amplification and primers
      specific for nine of the mammalian connexins, we have found that normal rat and
      mouse pancreas contain six connexin transcripts, including one that codes for
      alpha 6 connexin, a protein also referred to as Cx45. This transcript was also
      identified in isolated pancreatic islets, in FACS-purified suspensions of primary
      beta cells and in the insulin-producing cells of an experimental tumor. Using
      antibodies, we found that connexin alpha 6 is expressed by the latter cells, as
      well as by pancreatic fibroblasts and epithelial duct cells. The data show that
      pancreatic islets have a normal prenatal development in mice that no longer
      express alpha 1 connexin. They further provide evidence that normal and tumoral
      insulin-producing cells natively coexpress connexins alpha 1 and alpha 6.

PMID- 10079508
TI  - Genetic factors influence cataract formation in alpha 3 connexin knockout mice.
AB  - Connexin alpha 3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear
      cataracts shortly after birth. A large variance in the cataracts was observed in
      alpha 3 null sibs on a mixed 129SvJae X C57BL/6J F3 background. This suggested
      that the genetic background might influence the cataract phenotype. Therefore, we
      placed the alpha 3 null mutation into a 129SvJae background, and also backcrossed
      the mutation for six generations into 129SvJ and C57BL/6J backgrounds. While
      alpha 3 nulls on the two 129 backgrounds contained severe cataracts associated
      with gamma crystallin cleavage, alpha 3 nulls on the C57B16 background had far
      milder cataracts with no detectable gamma crystallin cleavage. These findings
      suggest that a genetic modifier exists that influences gamma crystallin
      stability, and that gamma crystallin breakdown is associated with severe nuclear
      cataracts.

PMID- 10079509
TI  - Roles for alpha 1 connexin in morphogenesis of chick embryos revealed using a
      novel antisense approach.
AB  - Gap junctional communication has been implicated in embryonic development and
      pattern formation. The gap junction protein, alpha 1 connexin (Cx43) is expressed
      in dynamic and spatially restricted patterns in the developing chick embryo and
      its expression correlates with many specific developmental events. High levels of
      expression are found in regions of budding, which leads to shaping and appears to
      be a necessary prelude for tissue fusions. In order to investigate the role of
      alpha 1 connexin in these morphogenetic events, we developed a novel method of
      applying unmodified antisense deoxyoligonucleotides (ODNs) to chick embryos. The
      use of pluronic gel to deliver antisense ODNs has allowed us to regulate the
      expression of alpha 1 connexin protein, both spatially and temporally. This
      "knockdown" results in some striking developmental defects that mimic some common
      congenital abnormalities, such as spina bifida, anencephaly, myeloschisis, limb
      malformation, cleft palate, failure of hematopoiesis, and cardiovascular
      deformity. The results imply a major role for alpha 1 connexin communication in
      the integration of signaling required for pattern formation during embryonic
      development. This novel antisense technique may also be widely applicable.

PMID- 10079510
TI  - Antisense oligonucleotide blockade of connexin expression during embryonic bone
      formation: evidence of functional compensation within a multigene family.
AB  - Prior studies in our laboratory demonstrated the presence of gap junction
      proteins (connexins) throughout intramembranous bone formation [Minkoff et al.
      (1994) Anat Embryol 190:231-241]. In addition, two members of the connexin family
      of gap junction proteins, connexin 43 (Cx43; Gj alpha 1) and connexin 45 (Cx45;
      Gj alpha 6), were found by Civitelli et al. [1993; J Clin Invest 91:1888-1896] to
      be associated, specifically, with osteogenesis. Recently, however, a null
      mutation in the gene encoding Gj alpha 1 in mice has been produced by Reaume et
      al. [1995; Science 267:1831-1834]. Gj alpha 1 null homozygotes survived to term
      but died at birth of heart abnormalities. Examination of the null homozygous
      embryos, surprisingly, did not reveal overt histological or anatomical
      abnormalities in any organ system other than the heart. In view of this, the
      present investigation was initiated in order to evaluate bone formation under
      conditions in which the expression of Gj alpha 1 and Gj alpha 6, the connexins
      specifically associated with osteogenesis, had been perturbed, individually as
      well as in combination. An in vitro system employing organ cultures of
      dissociated embryonic chick mandibular mesenchyme was employed. Mesenchyme was
      cultured in the presence and absence of sense and antisense oligodeoxynucleotides
      (ODN), ranging in length from 15 to 24 mer and containing sequences that included
      the initiation codon of Gj alpha 1 and of Gj alpha 6. In cultures of mesenchyme,
      grown for 6 to 13 days in the presence of the combined antisense ODNs to Gj alpha
      1 and Gj alpha 6, bone formation was markedly reduced or absent. By contrast, in
      cultures grown in medium containing the combination of corresponding sense ODNs
      to both Gj alpha 1 and Gj alpha 6, bone formation was evident. In addition, when
      cultures were grown in the presence of antisense or sense ODNs to either Gj alpha
      1 or Gj alpha 6, individually, bone formation was seen. Immunohistochemical
      analysis of connexin expression revealed intense immunoreactive signal to Gj
      alpha 1 and Gj alpha 6 in bone of the control explants, in which no ODNs were
      present; in those cultures in which either Gj alpha 1 and Gj alpha 6 antisense
      ODNs were present, however, the expression of the respective connexin protein was
      either significantly reduced or absent. Further, in those explants in which Gj
      alpha 1 expression was blocked, immunoreactive signal to Gj alpha 6 appeared to
      have been amplified in regions of developing bone. These results suggest that, in
      avian osteogenic tissue, when Gj alpha 1 protein expression has been impeded
      another related connexin protein (Gj alpha 6) may subserve the functions of the
      missing connexin. The findings of this study, therefore, support the hypothesis
      that, within the connexin gene family, functional compensation can occur.

PMID- 10079511
TI  - Gap-Junctional communication between developing Drosophila muscles is essential
      for their normal development.
AB  - Recent experiments have demonstrated that a family of proteins, known as the
      innexins, are structural components of invertebrate gap junctions. The shaking-B
      (shak-B) locus of Drosophila encodes two members of this emerging family, Shak
      B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap
      junctions in the development of embryonic and larval muscle. During
      embryogenesis, shak-B transcripts are expressed in a subset of the somatic
      muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in
      ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild
      type early stage 16 embryos spreads, via gap junctions, to label adjacent
      muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural)
      function is disrupted), dye injected into VO4 fails to spread into other muscles.
      In the first instar larva, when dye coupling between muscles is no longer
      present, another effect of the shak-B2 mutation is revealed by whole-cell voltage
      clamp. In a calcium-free saline, only two voltage-activated potassium currents
      are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2
      larvae, these two currents are significantly reduced in magnitude in VO4 and 5,
      but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background
      fully rescues both dye coupling in embryonic muscle and whole-cell currents in
      first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set
      of embryonic gap-junction proteins, and that it is required for the normal
      temporal development of potassium currents in some larval muscles.

PMID- 10079512
TI  - Gap junction blockage interferes with neuronal and astroglial differentiation of
      mouse P19 embryonal carcinoma cells.
AB  - During embryonic development, cells not only increase in number, they also
      undergo specialization and differentiate into diverse cell types that are
      organized into different tissues and organs. Nervous system development, for
      example, involves a complex series of events such as neuronal and astroglial
      differentiation that are coordinated among adjacent cells. The organization of
      growth and differentiation may be mediated, at least partly, by exchange of small
      ions and molecules via intercellular gap junction channels. These structures are
      mode of connexons (hemichannels), which are hexameric assemblies of the gap
      junction proteins, connexins. We investigated the role of intercellular
      communication in neuronal and astroglial differentiation by using a gap junction
      blocking agent, carbenoxolone (CBX), in comparison to its inactive (control)
      analog, glycyrrhizic acid (GZA). We used the mouse P19 embryonal carcinoma cell
      line, which differentiates into neurons and astrocytes upon retinoic acid (RA)
      induction. Our results show that both GZA- and CBX-treated cells express alpha 1
      connexin (connexin43). The level of alpha 1 connexin decreases upon RA induction.
      CBX treated cells show significant reduction in both neuronal (5-fold) and
      astrocytic (13-fold) differentiation compared with those of control. These
      results clearly indicate that the blockage of gap junction-mediated intercellular
      communication interferes with differentiation of P19 cells into neurons and
      astrocytes.

PMID- 10079513
TI  - Connexin45 (alpha 6) expression delineates an extended conduction system in the
      embryonic and mature rodent heart.
AB  - We previously demonstrated that alpha 6 (Cx45), one of the three connexins of the
      mammalian myocardium, is preferentially expressed in the peripheral portion of
      the ventricular conduction system in rats and mice. Here we report that alpha 6
      is also prominently immunolocalized in the atrioventricular node and His bundle
      of these species. The distribution of immunolocalized alpha 6 reveals that the
      node and bundle form part of an extended central conductive network
      circumscribing the AV and outflow junctional regions of the fetal, and less
      continuously, the adult heart. Of the three cardiac connexins, alpha 6 is the
      isoform most continuously expressed by conduction tissues, and may thus account
      for the recently reported viability of the alpha 5 (Cx40) knockout mouse. It is
      concluded that alpha 6 expression is a defining feature of the heterogenous
      tissues comprising the atrioventricular conduction system of the rodent heart.

PMID- 10079514
TI  - Suppression of human prostate cancer cell growth by forced expression of connexin
      genes.
AB  - The cell-to-cell channels in gap junctions, formed of proteins called connexins
      (Cxs), provide a direct intercellular pathway for the passage of small signaling
      molecules (< or = 1 kD) between the cytoplasmic interiors of adjoining cells. It
      has been proposed that alteration in the expression and function of Cxs may be
      one of the genetic changes involved in the initiation of neoplasia. To elucidate
      the role of Cxs in the pathogenesis of human prostate cancer (PCA), the pattern
      of expression of Cx alpha 1 (Cx43) and Cx beta 1 (Cx32) was studied by
      immunocytochemical analysis in normal prostate and in prostate tumors of
      different histological grades. While normal prostate epithelial cells expressed
      only Cx beta 1, both Cx alpha 1 and Cx beta 1 were detected in PCA cells. The Cxs
      were localized at the cell-cell contact areas in normal prostate and well
      differentiated prostate tumors; however, as prostate tumors progressed to more
      undifferentiated stages, the Cxs were localized in the cytoplasm, followed by an
      eventual loss in advanced stages. Thus, epithelial cells from prostate tumors
      showed subtle and gross alterations with regard to expression of Cx alpha 1 and
      Cx beta 1 and their assembly into gap junctions during the progression of PCA.
      Retroviral-mediated transfer of Cx alpha 1 and Cx beta 1 into a Cx-deficient
      human PCA cell line, LNCaP, inhibited growth, retarded tumorigenicity, and
      induced differentiation, and these effects were contingent upon the formation of
      gap junctions. In addition, the capacity to form gap junctions in most Cx
      transduced LNCaP cells was lost upon serial passage. Taken together, these
      findings indicate that the control of proliferation and differentiation of
      epithelial cells in prostate tumors may depend on the appropriate assembly of Cx
      beta 1 and Cx alpha 1 into gap junctions and that the development of PCA may
      involve the positive selection of cells with an impaired ability to form gap
      junctions.

PMID- 10079515
TI  - Quiescent mammary epithelial cells have reduced connexin43 but maintain a high
      level of gap junction intercellular communication.
AB  - Gap junctions have been implicated in growth control, but it remains unclear
      whether cells that enter a quiescent state continue to express connexins and
      maintain a high level of gap junction intercellular communication (GJIC). To this
      end, MAC-T cells, a bovine mammary epithelial cell line, were serum starved for
      48 h to induce a quiescent (G0) state. In quiescent cells, [3H]thymidine
      incorporation was reduced by 97.3% from serum-fed controls. Western blotting in
      conjunction with Phosphorlmager analysis revealed up to a 20-fold decrease in the
      expression of the gap junction protein connexin43 (Cx43 or alpha 1) and a shift
      toward the unphosphorylated form in quiescent cells. However, cell-to-cell
      transfer of the gap junction-permeable fluorescent tracer, Lucifer yellow, was
      only moderately reduced in quiescent cells. In control cells, Cx43 was
      predominantly perinuclear, although it was also present at sites of cell-cell
      apposition. In quiescent cells, intracellular labeling for Cx43 decreased without
      a corresponding reduction at areas of cell-cell contact. Recovery from serum
      deprivation resulted in increased thymidine incorporation that corresponded with
      an elevation in Cx43 protein expression and phosphorylation. In parallel studies,
      MAC-T cells were also induced to enter a quiescent state through contact
      inhibition. Despite a 20-fold reduction in 5-bromo-2'-deoxyuridine and a
      substantial reduction in intracellular Cx43, contact inhibited MAC-T cells also
      maintained gap junctions and GJIC. These experiments demonstrate that the
      maintenance of dye coupling in quiescent mammary cells is correlated with a
      redistribution of intracellular stores of Cx43.

PMID- 10079516
TI  - Connexin diversity and gap junction regulation by pHi.
AB  - The molecular mechanisms controlling pH-sensitivity of gap junctions formed of
      two different connexins are yet to be determined. We used a proton-sensitive
      fluorophore and electrophysiological techniques to correlate changes in
      intracellular pH (pHi) with electrical coupling between connexin-expressing
      Xenopus oocytes. The pH sensitivities of alpha 3 (connexin46), alpha 2
      (connexin38), and alpha 1 (connexin43) were studied when these proteins were
      expressed as: 1) nonjunctional hemichannels (for alpha 3 and alpha 2), 2)
      homotypic gap junctions, and 3) heterotypic gap junctions. We found that alpha 3
      hemichannels are sensitive to changes in pHi within a physiological range (pKa =
      7.13 +/- 0.03; Hill coefficient = 3.25 +/- 1.73; n = 8; mean +/- SEM); an even
      more alkaline pKa was obtained for alpha 2 hemichannels (pKa = 7.50 +/- 0.03;
      Hill coefficient = 3.22 +/- 0.66; n = 13). The pH sensitivity curves of alpha 2
      and alpha 3 homotypic junctions were indistinguishable from those recorded from
      hemichannels of the same connexin. Based on a comparison of pKa values, both
      alpha 3 and alpha 2 gap junctions were more pHi-dependent than alpha 1. The pH
      sensitivity of alpha 2-containing heterotypic junctions could not be predicted
      from the behavior of the two connexons in the pair. When alpha 2 was paired with
      alpha 3, the pH sensitivity curve was similar to that obtained from alpha 2
      homotypic pairs. Yet, pairing alpha 2 with alpha 1 shifted the curve similar to
      homotypic alpha 1 channels. Pairing alpha 2 with a less pH sensitive mutant of
      alpha 1 (M257) yielded the same curve as when alpha 1 was used. However, the pH
      sensitivity curve of alpha 3/alpha 1 channels was similar to alpha 3/alpha 3,
      while alpha 3/M257 was indistinguishable from alpha 3/alpha 1. Our results could
      not be consistently predicted by a probabilistic model of two independent gates
      in series. The data show that dissimilarities in the pH regulation of gap
      junctions are due to differences in the primary sequence of connexins. Moreover,
      we found that pH regulation is an intrinsic property of the hemichannels, but pH
      sensitivity is modified by the interactions between connexons. These interactions
      should provide a higher level of functional diversity to gap junctions that are
      formed by more than one connexin.

PMID- 10079517
TI  - Developmental expression and molecular characterization of two gap junction
      channel proteins expressed during embryogenesis in the grasshopper Schistocerca
      americana.
AB  - Gap junctions are membrane channels that directly connect the cytoplasm of
      neighboring cells, allowing the exchange of ions and small molecules. Two
      analogous families of proteins, the connexins and innexins, are the channel
      forming molecules in vertebrates and invertebrates, respectively. In order to
      study the role of gap junctions in the embryonic development of the nervous
      system, we searched for innexins in the grasshopper Schistocerca americana. Here
      we present the molecular cloning and sequence analysis of two novel innexins, G
      Inx(1) and G-Inx(2), expressed during grasshopper embryonic development. The
      analysis of G-Inx(1) and G-Inx(2) proteins suggests they bear four transmembrane
      domains, which show strong conservation in members of the innexin family. The
      study of the phylogenetic relationships between members of the innexin family and
      the new grasshopper proteins suggests that G-Inx(1) is orthologous to the
      Drosophila 1(1)-ogre. However, G-Inx(2) seems to be a member of a new group of
      insect innexins. We used in situ hybridization with the G-Inx(1) and G-Inx(2)
      cDNA clones, and two polyclonal sera raised against different regions of G-Inx(1)
      to study the mRNA and protein expression patterns and the subcellular
      localization of the grasshopper innexins. G-Inx(1) is primarily expressed in the
      embryonic nervous system, in neural precursors and glial cells. In addition, a
      restricted stripe of epithelial cells in the developing limb, involved in the
      guidance of sensory growth cones, expresses G-Inx(1). G-Inx(2) expression is more
      widespread in the grasshopper embryo, but a restricted expression is found in a
      subset of neural precursors. The generally different but partially overlapping
      expression patterns of G-Inx(1) and G-Inx(2) supports the combinatorial character
      of gap junction formation in invertebrates, an essential property to generate
      specificity in this form of cell-cell communication.

PMID- 10079518
TI  - Expression of the myosin heavy chain genes in the tail muscle of thyroid hormone
      induced metamorphosing Rana catesbeiana tadpoles.
AB  - In tadpoles of the North American bullfrog, Rana catesbeiana, spontaneous and
      thyroid hormone (T3)-induced metamorphosis is characterized by regression of the
      tail, which is preceded by a decrease in total protein synthesis in tail tissues.
      We have demonstrated that thyroid hormone treatment of a tadpole does not affect
      the synthesis of all proteins equally in the tadpole tail muscle. For example,
      the synthesis of myosin heavy chains (MHCs) is depressed within 1 day and
      decreases to 45% of control values after 5 days of T3 treatment, whereas the
      decreased synthesis of soluble muscle proteins is transient and returns to above
      control levels by day 5. To determine whether the hormone-induced decrease in MHC
      synthesis is the result of changes in the transcription of translation of MHC
      mRNAs, we isolated cDNAs complementary to five different MHC mRNAs from a tail
      muscle cDNA library and used them to examine the levels of each MHC mRNA in the
      tail muscle of T3-treated tadpoles. mRNAs that recognize the cDNAs for these five
      different MHCs are all expressed in the tadpole tail and limb muscles, as well as
      in the adult leg muscles. MHC mRNAs unique to tadpole tail were not detected.
      Interestingly, the relative amounts of mRNA for four of the five MHCs increase in
      tail muscle after T3 treatment of the tadpole, suggesting that repression of MHC
      gene expression at the protein level does not result from a decrease in the
      amount of MHC mRNAs. Rather, these results support the contention that the
      decreased synthesis of MHCs in the tail muscle of T3-treated tadpoles is caused
      by this hormone, either directly or indirectly, depressing the translation of the
      MHC mRNAs in this tissue. These results, coupled with the observation that the
      synthesis of soluble muscle proteins is depressed only in a transient fashion,
      suggest that T3 may be initiating the expression of a gene(s) that encodes a
      protein(s) responsible for inhibiting the translation of the MHCs and, perhaps,
      other structural proteins in the tadpole tail muscle. Whatever the case, the
      translational regulation of MHC synthesis occurs well before any degradation of
      the tail tissue is evident and appears to be one of the earliest events in the
      hormone-induced cell death program of the tadpole tail muscle.

PMID- 10079519
TI  - Sequence and expression analysis of Nhlh1: a basic helix-loop-helix gene
      implicated in neurogenesis.
AB  - Nhlh1 is a basic helix-loop-helix (bHLH) gene that has been implicated in mouse
      neurogenesis. Previous studies have shown it to be expressed in regions in which
      there are differentiating neurons during late embryonic and fetal development,
      but detailed studies of the role of Nhlh1 earlier in embryonic development have
      not been performed. In this paper, we examine the expression of Nhlh1 transcripts
      at early embryonic stages (E8.5-E10.5), at the onset of neurogenesis, and compare
      the pattern of expression with that of Islet-1, a marker of postmitotic neurons.
      We show that Nhlh1 is expressed in early postmitotic neurons but is down
      regulated as these cells migrate from the ventricular zone. We have also
      determined the genomic structure of mouse Nhlh1 and have characterised the
      promoter sequence, as a first step towards identifying factors that may control
      Nhlh1 expression. Nhlh1 has been implicated previously as a candidate for the
      neural tube defect mutant loop-tail (Lp); here, we present sequence and
      expression data indicating that Nhlh1 is unlikely to be responsible for the Lp
      mutation.

PMID- 10079520
TI  - N-Cadherin expression and signaling in limb mesenchymal chondrogenesis:
      stimulation by poly-L-lysine.
AB  - Cellular condensation is a requisite step in the initiation of mesenchymal
      chondrogenesis in the embryonic limb bud. We have previously shown that cellular
      condensation of limb chondroprogenitor mesenchymal cells is accompanied by
      elevated expression of N-cadherin during chondrogenesis both in vivo and in
      vitro. N-Cadherin-mediated cell-cell interaction is also functionally required
      for proper mesenchymal chondrogenesis both in vivo and in vitro. In this report,
      we have further analyzed the functional importance of N-cadherin in the cellular
      condensation-chondrogenesis pathway by examining N-cadherin expression and
      related activities in high density micromass cultures of chick limb mesenchymal
      cells in which chondrogenesis is being stimulated with the cationic polymer, poly
      L-lysine (PL). The chondrogenesis-promoting action of PL is thought to involve
      the clustering of cells via ionic cross-linking, perhaps mimicking the action of
      an endogenous matrix component. Immunohistochemistry, immunoblotting, and
      Northern blot analysis all show that PL treatment results in a time-dependent
      increase in N-cadherin expression at both the protein and mRNA levels. In
      addition, inhibition of N-cadherin function with a neutralizing monoclonal
      antibody directed to its extracellular domain inhibits the chondrogenesis
      stimulating effect of PL. PL treatment also alters the tyrosine-phosphorylation
      state of the N-cadherin associated signaling protein, beta-catenin. These results
      suggest that N-cadherin-mediated cell adhesion is a requisite regulatory
      component of the limb mesenchymal chondrogenic differentiation program, involving
      at least in part beta-catenin tyrosine phosphorylation as a signaling step.

PMID- 10079521
TI  - The Sinorhizobium meliloti insertion sequence (IS) elements ISRm102F34-1/ISRm7
      and ISRm220-13-5 belong to a new family of insertion sequence elements.
AB  - The Sinorhizobium meliloti insertion sequence (IS) elements ISRm102F34-1 and
      ISRm220-13-5 are 1481 and 1550 base pairs (bp) in size, respectively. ISRm102F34
      1 is bordered by 15 bp imperfect terminal inverted repeat sequences (two
      mismatches), whereas the terminal inverted repeat of ISRm220-13-5 has a length of
      16 bp (two mismatches). Both insertion sequence elements generate a 6-bp target
      duplication upon transposition. The putative transposase enzymes of ISRm102F34-1
      and ISRm220-13-5 consist of 449 or 448 amino acid residues with predicted
      molecular weights of 50.7 or 51.3 kDa and theoretical isoelectric points of 10.8
      or 11.1, respectively. ISRm102F34-1 is identical in 98.9% of its nucleotide
      sequence to an apparently inactive copy of an insertion sequence element,
      designated ISRm7, which flanks the left-end of the nodule formation efficiency
      (nfe) region of plasmid pRmeGR4b of S. meliloti strain GR4. ISRm102F34-1 and
      ISRm220-13-5 are closely related since they show an overall identity of 57.0% at
      the nucleotide sequence level and of 47.3% at the deduced amino acid level of
      their putative transposases. Both insertion sequence elements displayed
      significant similarity to the Xanthomonas campestris ISXc6 and its homolog
      IS1478a. Since none of these insertion sequence elements could be allocated to
      existing families of insertion sequence elements, a new family is proposed.
      Analysis of the distribution of ISRm102F34-1/ISRm7 in various local S. meliloti
      populations sampled from Medicago sativa, Medicago sphaerocarpa and Melilotus
      alba host plants at different locations in Spain revealed its presence in 35% of
      the isolates with a copy number ranging from 1 to 5. Furthermore, ISRm102F34
      1/ISRm7 homologs were identified in other rhizobial species.

PMID- 10079522
TI  - Identification of Bordetella pertussis virulence-associated outer membrane
      proteins.
AB  - Bordetella pertussis virulence-associated 30-, 32-, 90- and 95-kDa outer membrane
      proteins were purified and their N-terminal amino acid sequences were determined.
      The 30- and 32-kDa outer membrane proteins showed identity to the C-terminal
      region of the precursors of the serum resistance protein (BrkA) and the tracheal
      colonization factor, respectively. We confirmed the cleavage site of these
      precursors after N731 for BrkA and after N393 for tracheal colonization factor.
      Associated with the 32-kDa outer membrane protein, we found a new group of 36-kDa
      virulence-associated peptides. The 95-kDa outer membrane protein showed identity
      to Vag8. The 90-kDa outer membrane protein did not show homology with the
      described proteins. We report the N-termini sequence of Vir-90, a novel potential
      virulence factor.

PMID- 10079523
TI  - Phylogenetic relationships between toxic and non-toxic strains of the genus
      Microcystis based on 16S to 23S internal transcribed spacer sequence.
AB  - 16S to 23S ribosomal DNA internal transcribed spacer sequences of 47 strains of
      the genus Microcystis were determined. Derived maximum likelihood and DNA
      distance trees indicated that Microcystis can be divided into three clusters. The
      first cluster included toxic and non-toxic strains, the second only toxic ones,
      and the third only non-toxic ones. The tree topologies were not necessarily
      correlated with morphospecies distinction or phycobilin pigment composition, and
      one genotype may have more than one morphotype. Phylogenetic analysis based on
      intergenic spacer sequences was thought to be effective for understanding
      relationships among closely related species and strains.

PMID- 10079524
TI  - An apoptotic response by J774 macrophage cells is common upon infection with
      diarrheagenic Escherichia coli.
AB  - Representative strains of the different diarrheagenic Escherichia coli virotypes
      were tested for their potential cytotoxicity in the J774 macrophage cell line.
      All the seven virotypes of E. coli were cytotoxic to J774 macrophages, and in
      most cases the bacteria induced an apoptotic response. With the exception of the
      enterotoxigenic E. coli (ETEC) strain, all the other six virotypes caused
      induction of apoptosis as evidenced by quantitative analysis of the
      characteristic DNA fragmentation at the individual cell level. These results
      suggest that apoptosis could be one of the mechanisms contributing to the
      diarrheal disease development.

PMID- 10079525
TI  - Effect on cell surface hydrophobicity and susceptibility of Helicobacter pylori
      to medicinal plant extracts.
AB  - Effects on aqueous extracts of medicinal plants on ten Helicobacter pylori
      strains were studied by the salt aggregation test to determine the possibility to
      modulate their cell surface hydrophobicity and by an agar diffusion assay for
      detection of antimicrobial activity. It was established that aqueous extracts of
      bearberry and cowberry leaves enhance cell aggregation of all H. pylori strains
      tested by the salt aggregation test, and the extract of bearberry possessed a
      remarkable bacteriostatic activity. Pure tannic acid showed a result similar to
      that of bearberry and cowberry extracts which contained a large amount of
      tannins. In contrast, extracts of wild camomile and pineapple-weed, which blocked
      aggregation of H. pylori, contained small amounts of tannins and did not reveal
      any antimicrobial activity. Tannic acid seems to be the component of bearberry
      and cowberry aqueous extracts with the highest activity to decrease cell surface
      hydrophobicity as well as in antibacterial activity against H. pylori.

PMID- 10079526
TI  - Isolation and characterization of a DNA probe for Staphylococcus aureus
      subspecies aureus biovar.
AB  - The gene encoding for polynucleotide phosphorylase (pnp) of a new biovar of
      Staphylococcus aureus subsp. aureus (NBSA) has been isolated from a genomic
      library of strain M280(0). The coding region consisted of a 1094-bp HindIII
      HindIII DNA fragment encoding for a protein of 277 amino acids with a calculated
      molecular mass of 29.5 kDa. The nucleotide sequence of the structural gene,
      contained a continuous open reading frame of 836 bp, showed significant homology
      with the genes of bacterial polynucleotide phosphorylase from Bacillus subtilis
      (67.7% identity), from Haemophilus influenzae (62.4% identity), from Pseudomonas
      luminescens (61.6% identity), and from Escherichia coli (59.7% identity). DNA-DNA
      and DNA-colony slot-blot hybridizations demonstrated that the pnp gene, employed
      as a molecular probe, is specific for the identification of NBSA strains.

PMID- 10079527
TI  - Stimulation of bacterial growth by heat-stable, norepinephrine-induced
      autoinducers.
AB  - The ability of norepinephrine to increase the growth of Escherichia coli in a
      serum-based medium has previously been shown to be due to the production of an
      autoinducer of growth during early log phase. Seventeen Gram-negative and 6 Gram
      positive clinical isolates were examined for a similar ability to respond to
      norepinephrine, and to synthesise autoinducer. The majority of Gram-negative
      strains both produced and responded to heat-stable norepinephrine-induced
      autoinducers of growth. Most of these autoinducers showed a high degree of cross
      species activity, suggesting the existence of a novel family of Gram-negative
      bacterial signalling molecules. In contrast, although a number of Gram-positive
      strains were able to respond to norepinephrine, the majority failed to produce
      autoinducers in the presence of norepinephrine.

PMID- 10079528
TI  - Adhesion of four Bifidobacterium strains to human intestinal mucus from subjects
      in different age groups.
AB  - The number of bifidobacteria in faeces and intestinal contents has been shown to
      be reduced with increasing age of the subject. The adhesion of four
      Bifidobacterium strains was tested to mucus isolated from subjects of different
      age. All strains bound significantly less to mucus isolated from elderly
      subjects, compared to mucus from the other age groups. Two of the tested strains
      also showed decreased adhesion to mucus isolated from 6-month-old and adult
      subjects compared to the adhesion to mucus from 2-month-old subjects. The results
      suggest that reduced adhesion may be a factor involved in the decreasing
      colonisation of elderly subjects by bifidobacteria.

PMID- 10079529
TI  - Characterisation of kinetoplast DNA minicircles from Herpetomonas samuelpessoai.
AB  - In this study, we have sequenced more than 100 clones of minicircle DNA from
      Herpetomonas samuelpessoai. An unusual amplification approach was developed to
      amplify minicircle DNA by using a pair of complementary primers designed from a
      universal stretch of minicircle sequence. Sequence analysis shows that the
      kinetoplast minicircles in Herpetomonas with a size of 1.3 kb are organised into
      two conserved regions and two variable regions which are located 180 degrees
      apart. The potential gRNA genes are encoded in variable regions of minicircle
      approximately 360 bp from CSB-3 (conserved sequence block 3). A conserved
      upstream sequence located 30 nt before the gRNA genes was identified and is
      related to the gRNA genes in sequence organisation. A potential role(s) of this
      sequence in gRNA transcription is discussed.

PMID- 10079530
TI  - The ability of Vibrio vulnificus to use a synthetic hydrophilic heme compound, Fe
      TPPS, as a single iron source.
AB  - Vibrio vulnificus, an opportunistic human pathogen, can obtain iron from a
      variety of heme proteins. This process involves the digestion of heme proteins by
      an exoprotease to liberate protoheme (iron-protoporphyrin IX). In the present
      study, we tested whether this pathogen also uses a synthetic heme compound, Fe
      alpha,beta,gamma,delta-tetraphenylporphine tetrasulfonic acid (Fe-TPPS), as an
      iron source. When inoculated into a medium containing Fe-TPPS, V. vulnificus L
      180 multiplication was seen to be dependent on the concentration of the synthetic
      heme compound; a mutant lacking the ability to utilize protoheme did not
      multiply. Cells of the strain grown under the iron-restricted condition showed
      time-dependent uptake of Fe-TPPS. The ability to use either protoheme or Fe-TPPS
      was significantly reduced by the addition of an excess amount of free TPPS or Cu
      TPPS. The data suggest that, V. vulnificus may assimilate Fe-TPPS, at least
      partially, through the same system as that for protoheme.

PMID- 10079531
TI  - Prevalence of nim genes in anaerobic/facultative anaerobic bacteria isolated in
      South Africa.
AB  - This study investigated the prevalence of nim genes (proposed to encode a 5
      nitroimidazole resistance product) in 64 anaerobic/facultative anaerobic
      bacteria. Employing universal nim gene primers, 458-bp amplified fragments were
      recorded as presumptive positives in 22/64 strains at an annealing temperature of
      52 degrees C and 15/64 strains at 62 degrees C, of which seven were
      propionibacteria. DNA sequencing confirmed the presence of nimA genes in
      Propionibacterium spp. (five strains), Actinomyces odontolyticus (one strain),
      Prevotella bivia (one strain) and Clostridium bifermentans (one strain) and nimB
      genes from five strains of Bacteroides fragilis. nimA genes were predominant in
      propionibacteria indicating a potential nimA gene source in anaerobic
      environments.

PMID- 10079532
TI  - Phylogenetic analysis of transformable strains of thermophilic Bacillus species.
AB  - Few strains of thermophilic Bacillus spp are readily transformable with plasmid
      DNA. Given the considerable phylogenetic and phenotypic diversity amongst
      thermophilic bacilli, we have examined whether transformability is a trait
      associated with a particular phylogenetic group, by sequencing the 16S ribosomal
      RNA genes from transformable strains NUB3621, K1041, and NRRL1174. Although all
      of these strains were described in the literature as B. stearothermophilus, only
      NRRL1174 is closely related to the type strain of this species. Based on its 16S
      rDNA sequence and physiological data K1041 appeared to belong to the species B.
      thermodenitrificans, while NUB3621 showed a slightly closer relationship to B.
      thermoglucosidasius than to B. stearothermophilus. Therefore we conclude that the
      trait of transformability, though possibly strain-specific, is not limited to a
      single species of thermophilic Bacillus.

PMID- 10079533
TI  - Interaction of Escherichia coli heat-stable enterotoxin B with rat intestinal
      epithelial cells and membrane lipids.
AB  - The binding of 125I-labeled Escherichia coli heat-stable enterotoxin B to rat
      intestinal epithelial cells was unsaturable and nonspecific, at concentrations
      well above that required to mediate biological events. Following its interaction
      with intestinal cells, approximately 50-80% of heat-stable enterotoxin B remained
      stably associated with the cells, implying that it was partitioned into the
      membrane and/or internalized by the cell. The toxin bound with different
      affinities to lipids isolated from intestinal epithelial cells, phospholipids,
      glycolipids, neutral lipids and to model membrane vesicles containing negatively
      charged lipids. These results indicate that heat-stable enterotoxin B utilizes
      the membrane bilayer, rather than a surface protein or glycoprotein in modulating
      toxin-induced enterotoxicity.

PMID- 10079534
TI  - [Calcium, nutrition and osteoporosis].

PMID- 10079535
TI  - [Characteristics of the carriers of antibodies to hepatitis C virus with normal
      transaminases levels in HIV infected patients].
AB  - BACKGROUND: To know the characteristics of the carriers of antibodies to
      hepatitis C virus (HCV) with persistently normal transaminases levels
      ("carriers") in coinfected with HIV, the incidence of the real viral activity and
      the factors that could determine it. PATIENTS AND METHODS: We analyzed 114
      patients with criteria for chronic hepatitis C, 41 with detectable antibodies
      (anti-HCV), but without chemical evidence of a deteriorations of the liver
      function, all of them infected with HIV. In 6 patients was possible to determine
      the genotype of the HCV (INNO-LiPA HCV Innogenetics. Belgica) and in 32 the HCV
      RNA (Amplicor HCV Roche Diagnostics). We compared the characteristics that could
      be differential between both groups, investigating the possible factors that
      could define the group of "carriers" with detectable viral activity. RESULTS:
      From the 32 "carriers" in which we could determine the HCV-RNA, 15 (46.8%) had a
      positive result. The incidence of women in the "carriers" group was higher (41.4%
      vs 22.8%) (p < 0.05). The serum levels of gammaglobulin (gr/dl) was higher in the
      chronic hepatitis group (2.23 +/- 0.6 vs 1.9 +/- 0.5) (p < 0.01); however, these
      levels were higher for the 15 patients RNA (-) patients (2.19 +/- 0.7 vs 1.66 +/-
      0.41) (p < 0.01). The genotype distribution of HCV found in the "carriers" group
      with detectable viremia was: genotype 1(5 patients), subtype la (3 patients),
      subtype lb (2 patients) an genotype 3 (3 patients). There was no significant
      difference with respect to age, sex, degree of immunosuppression or the length of
      the infection with HCV. CONCLUSIONS: Approximately half of our "carriers" of anti
      HCV without evidence of changes in the liver function, infected with HIV, show
      detectable viremia and so probably liver biopsy would be indicated. Women are
      more often "carriers" and the high levels of gammaglobulin could define the
      existence of a real viral activity.

PMID- 10079536
TI  - [Viremia levels of the chronic hepatitis c virus in HIV infected patients,
      clinical implications].
AB  - BACKGROUND: To know the clinical implications of the viremia level and its
      evolution in time of the hepatitis C virus (HCV) in patients with chronic
      hepatitis and infected with the Human Immunodeficiency Virus (HIV). PATIENTS AND
      METHODS: We have studied the viremia level of the HCV in a a 38 patients group
      with active chronic hepatitis and infected with the HIV, using a quantitative PCR
      technic (Amplicor HCV, Roche Diagnostics); we had histological data in 33 of
      these patients. In 20 patients was analyzed the evolution in time of the viremia
      level with two or three serialized measurements (20 and 10 patients
      respectively), throughout 7.5 and 14.8 months on the average. We have analyzed
      some aspects like the risky behaviors associated with transmission, the estimated
      time from the contagious, the degree of histological damage and the immunitary
      impairment. RESULTS: We have observed a tendency to present a higher viremia
      level (logarithmic expression) with longer evolution time from the infection (p =
      0.08). The viral load had an inverse relation with the degree of histological
      fibrosis (Light fibrosis: 4.5 +/- 0.8 log vs Severe fibrosis: 3.7 +/- 0.8 log) (p
      < 0.01) and a direct relation with the Knodell histological activity index (HAI),
      only with those patients with a lower fibrosis degree (p < 0.01). There was no
      relation between the viremia level of the HCV and the degree of immunosuppression
      measured by the CD4 lymphocyte count, at least in those patients in which it was
      higher than 200/mm3. We have not observed relations between the viral load and
      the age or the transaminases level. The evolution in time of the viremia tended
      to rise from 3.7 +/- 1.3 to 4.5 +/- 0.9 log in 14.8 months on the average,
      although there were some cases with tendency to decrease. We have not observed
      relation between its increase/month and the degree of histological damage or the
      CD4 lymphocyte count. CONCLUSIONS: The viral load of the HCV in HIV-infected
      patients seems to have an inverse relation with the degree of liver fibrosis and
      direct relation with the histological activity when the fibrosis light and so it
      could indirectly inform us about the liver aggression. The degree of
      immunosuppression measured by the CD4 lymphocyte count, when these are > 200/mm3,
      doesn't seem to influence the viremia level of the HCV. The evolution of the
      viral load in time tend to rise although there could be some cases with
      intermittent or descending evolution, without these tendencies have any clinical
      implications.

PMID- 10079537
TI  - [Superior vena cava syndrome: a study based on 81 cases].
AB  - BACKGROUND: Characterize the etiology, clinical picture, radiographic findings,
      usefulness of several diagnostic studies in establishing an etiologic diagnosis,
      and outcome after treatment of superior vena cava syndrome (SVCS). METHODS: We
      reviewed the charts of all patients diagnosed of SVCS in our hospital between the
      years 1983 and 1996. RESULTS: Eighty-one patients (70 male, 11 female) with an
      average age of 61 years were included in the study. In 77 (95%) patients a
      neoplastic cause was diagnosed, mainly lung cancer (76%). The most common
      clinical findings were: feeling of fullness in the head (81%), edema of the face
      and arms (78%), jugular venous distention (75%), prominent venous pattern over
      the chest wall (73%), dyspnea (59%), and cough (37%). The average length of time
      from the onset of symptoms to the date of diagnosis was 28 days. The chest x-ray
      was abnormal in 78 (96%) cases: mediastinal widening (51%) and right hilar mass
      (48%) were the most common findings. The diagnosis of SVCS was evident (from
      clinical picture and chest roentgenogram) in 76 (94%) patients. In SVCS due to
      malignancy, the most productive investigations in establishing a pathologic
      diagnosis were bronchoscopy (54%) and biopsy of a superficial lymph node (18%).
      Partial or complete clinical response to treatment was achieved in seventy
      percent of the cases. CONCLUSIONS: SVCS is an uncommon entity and his most
      frequent cause is bronchogenic carcinoma. The characteristic clinical and
      radiographic findings allow to do a reliable diagnosis of the syndrome.
      Initially, clinical response (partial or complete) to treatment is achieved in
      most patients.

PMID- 10079538
TI  - [Clinical manifestations of Stenotrophomas (Xanthomonas) maltophilia infection].
AB  - OBJECTIVE: Stenotrophomonas maltophilia (SM) is a gram-negative bacillus whose
      incidence like nosocomial pathogen has been incremented in the last years,
      especially in immunocompromised patients, subjected to invasive procedures and
      those receiving broad-spectrum antimicrobial therapy. METHOD: We report 15
      isolations of SM between 1994-1996. RESULTS: The criteria for SM infection were
      fulfilled by 9 patients (60%), and 6 patients (40%) were colonized. The mean age
      of the patient was 60 +/- 12 years. Major predisposing factors in infections
      included venous catheterization (100%), prior surgery (86%), residence in ICU
      (80%), prior antibiotic therapy (80%) and intubation (66%). The most common
      underlying disease were heart disease (60%), treatment with immunosuppressors
      and/or steroids (46%) and chronic lung disease (46%). Ten cases (66%) had
      polymicrobial culture. The mortality rate was 40%. Risk factors associated with
      fatal outcome included the following: chronic lung disease (p = 0.043),
      nasogastric catheterization (p = 0.01), urinary tract catheterization (p = 0.02),
      intubation (p = 0.04) and the presence of pneumonia or sepsis by SM (p = 0.02).
      The most active agents were colistina (100%), cotrimoxazol (71%) and ceftazidima
      (53%). The isolates were highly resistant to first and second-generation
      cephalosporins (100%) tetracyclines (86%), aztreonam (91%) and imipenem (71%).
      CONCLUSION: SM cause a wide range of clinical syndromes and is more likely to
      cause infection or colonization in patients who have underlying disease. Due to
      its inherent multiple-antimicrobial resistance, it would appear its potential as
      a nosocomial pathogen will continue to increase. Therapy of patients should
      include cotrimoxazole.

PMID- 10079539
TI  - [A 73 year-old patient with thrombocytopenia and a giant cerebral vascular
      malformation].
AB  - We report the case of a patient who was seen by purpura and thrombocytopenia. The
      differential diagnosis in this patient included the presence of cerebral giant
      vascular malformation, the intake antiepileptic drugs and the presence of a
      chronic liver disease caused by viral hepatitis C infection. However the final
      diagnoses of Idiopathic Thrombocytopenia Purpura was made because of the presence
      of antiplatelets antibodies, the fluctuate evolution, and the increase of
      platelet count after costicosteroid therapy.

PMID- 10079540
TI  - [Gaucher's disease type I: an infrequent cause of portal hypertension].
AB  - Portal hypertension associated to Gaucher's disease type I with non cirrhotic
      liver involvement is a very in-equent finding. We report a case of Gaucher's
      disease type I without cirrhosis in which portal hypertension is the main
      manifestation. The mechanism of the portal hypertension is discussed in our
      report and can be related to an elevation in hepatic fluid resistance due to the
      Gaucher's cells compression on sinusoids.

PMID- 10079541
TI  - [Vibrio vulnificus septicemia in Spain].
AB  - Vibrio vulnificus is a virulent marine organism, able to contaminate sea-food. It
      usually produces bacteremia associated with secondary skin lesions in patients
      with underlying conditions, such as hepatic cirrhosis. We report a case of septic
      shock and characteristic skin lesions, due to Vibrio vulnificus in a patient with
      cirrhosis, who had eaten raw oysters. The patient survived in spite of the
      severity of the clinical picture. We conclude that Vibrio vulnificus infection
      must be considered in the differential diagnosis of sepsis and skin lesions.

PMID- 10079542
TI  - [Pulmonary lymphomatoid granulomatosis associated with AIDS. Report of a case and
      review of the literature].
AB  - We present an AIDs patient who was admitted to our hospital because of dry cough,
      pleuritic chest pain, fever and bilateral lung nodules on the chest X-ray. An
      open lung biopsy was diagnostic for Lymphomatoid Granulomatosis (GL). We review
      the literature of the clinical manifestations, anatomopathological and
      pathogenetic features, roentgenographic and laboratory findings, as well as
      treatment strategies of these patients. The GL has been described in association
      with AIDS, although in spite of the high prevalence of AIDS in our days, the
      association between these two entities is not frequent according to the few
      references in the literature.

PMID- 10079543
TI  - [Advances in pharmacological treatment of pituitary adenomas].
AB  - In last years, advances in endocrinological and neuroradiological research have
      lead to an earlier recognition and more effective management of pituitary
      tumours. At the same time, pharmacological investigation has allowed the
      development of useful drugs in the treatment of pituitary adenomas, either as an
      exclusive therapy or as an aid to surgery and radiotherapy. In this article we
      review indications and dosage of recently developed drugs for different types of
      hormone-secreting pituitary adenomas.

PMID- 10079544
TI  - [HLA: past, present and future].

PMID- 10079545
TI  - [Submucosa esophageal hematoma].

PMID- 10079546
TI  - [Pulmonary infection by Mycobacterium xenopi in a patient with positive HIV].

PMID- 10079547
TI  - [Paraneoplastic necrotizing myelopathy or intraspinal metastasis? A case review].

PMID- 10079548
TI  - [Virologic levels for HIV before and after the introduction of protease
      inhibitors].

PMID- 10079549
TI  - [A new case of Whipple's disease].

PMID- 10079550
TI  - [Idiopathic thrombocytopenic purpura and Graves disease: pathogenic questioning
      of a rare association].

PMID- 10079551
TI  - [Adult onset Still's disease after rickettsia infection].

PMID- 10079552
TI  - [Men and women physicians: is their professional practice different?].

PMID- 10079553
TI  - [The semFYC (Spanish Society of Family and Community Medicine) is becoming
      international: 1999, the beginning of the future].

PMID- 10079554
TI  - [Is therapy with local infiltrations feasible in primary care consultations?].
AB  - OBJECTIVE: To study the feasibility of local infiltration in primary care
      consultations. DESIGN: Before-and-after intervention study. SETTING: Two clinics
      at an urban health centre. PARTICIPANTS: Patients diagnosed with pathology of
      tender areas and treated with corticosteroid infiltration between May 1997 and
      May 1998. INTERVENTION: Corticoid infiltration plus local anaesthetic. Weekly
      check-up. Analysis of the variables: sex, age, diagnosis, time elapsed between
      indication and start of treatment, subjective assessment of pain before and after
      treatment (VRS scale), number of infiltrations per patient, side-effects.
      Evaluation of overall and individual effectiveness. RESULTS: 41 patients were
      infiltrated. Average age was 58. Most common pathologies were: rotary joint
      tendinitis (48.7%), anserine bursitis (24.4%), plantar fasciitis (7.3%). Average
      number of infiltrations per pathology: 1.3. Mean waiting time: 3.5 days.
      Comparison of pain by means of VRS (range 0-5) before and after treatment used
      the Wilcoxon test, with a statistically significant difference and p < 0.001 (z =
      -5.5109). For 35 patients (85.4%), pain was solved very well (values 0 and 1 on
      the VRS). For 3 patients (7.3%), improvement was moderate; and for 3 (7.3%) there
      was no improvement. CONCLUSIONS: 1. Treatment with local infiltration of
      corticosteroids is effective in dealing with pain, and is an alternative to
      treatment with NSAIDs. 2. It is feasible in primary care, and there are many
      advantages if the general practitioner employs this therapeutic technique.

PMID- 10079555
TI  - [The evolution of health and relationship habits of an adolescent cohort of
      Puerto de Sagunto (1995-1996)].
AB  - OBJECTIVE: To know the prevalence of tobacco consumption, alcohol and marihuana
      as well as the habits of relationship, in an adolescents cohort of 3rd of
      Obligatory Secondary Teaching (ESO), that accede for the first time to one of the
      four secondary school of Puerto de Sagunto and the evolution of these habits
      after a year of follow-up. DESIGN: Transverse observational study with data
      withdrawal in two moments. Site. In the four secondary school of Puerto de
      Sagunto (Valencia). PATIENT AND OTHERS PARTICIPANTS: Adolescent of 3rd of ESO
      that accede for the first time to the four secondary school of Puerto de Sagunto
      in the course 95-96. INTERVENTIONS: A self-fully validated habits poll of health
      and of relationship was given to the pupils of 3rd of ESO (n = 573), and a year
      after was given the same poll, to the pupils already in 4th of ESO (n = 395).
      MEASUREMENTS AND RESULTS: On health habits, were found meaningful statistic
      differences in various variables: in tobacco consumption several times to the
      month passes of the 30% to the 40%, in alcohol consumption more than proven
      passes of the 35% to the 52%, in have you intoxicated the response never passes
      of the 67% to the 57%, in the paragraph of marihuana consumption, the response
      never passes of the 82% to the 72%. On the habits of relationship were found
      significant statistic differences with respect to number of nocturnal exists
      during the week that goes from 1.07 to 1.33, the return hour before 10 passes of
      the 23% to the 8%, as well as the type of associations to those which belong,
      sports club passes of the 38% to the 46%. In the paragraph of relationship to
      their teachers, the response good passes of the 89% to the 93%. CONCLUSIONS: The
      step of 14 to 15 years supposes in this population an increase in alcohol
      consumption, tobacco and marihuana, they go out more days at night and return
      later to house, are associated more in sports clubs and have better relationships
      to their teachers. The knowledge of these habits permits the intervention with
      preventive programs, that attempt to change attitudes toward these toxic habits
      and to promote the healthiest.

PMID- 10079556
TI  - [The costs of treatment with the new antidepressants in clinical practice].
AB  - OBJECTIVE: To assess if, in usual clinical practice, the patterns of use of new
      antidepressant are associated to different health resource utilisation. DESIGN:
      Naturalistic, retrospective, observational study. SETTING: Urban health center.
      PATIENTS: DSM-IIIR diagnostic criteria of depressive disorder and treatment with
      a new antidepressant (n = 328). INTERVENTIONS: Information on resource
      utilisation was collected in those patients treated with fluoxetine (FLX),
      fluvoxamine (FLV) sertraline (SER), paroxetine (PAR) and venlafaxine (VLF).
      Direct, indirect and total costs were compared according to the different
      patterns of use (stable therapy, upward dose titration, switching or
      augmentation) and according to the initially prescribed antidepressant. The
      follow-up period was 6 months. RESULTS: Direct and total daily costs of those
      patients with unestable therapy (upward dose titration, switching or
      augmentation) were 55% (p < 0.01) and 87% (p = 0.001) higher than for patients
      with stable therapy, respectively. Patients who initiated therapy on SER, VLF and
      PAR had 35% (p < 0.05), 80% (p < 0.05) and 37% (p < 0.05), respectively, higher
      average total costs per day than patients who initiated therapy with FLX.
      Regarding direct costs, patients who initiated therapy on SER and VLF had 48% (p
      < 0.001) and 58% (p < 0.05) higher average costs per day than patients who
      initiated therapy with FLX. CONCLUSIONS: New antidepressants show different
      patterns of use in a clinical practice setting, being FLX the agent more
      associated to a stable pattern of use. The pattern of use is associated to
      different health resource utilisation. Patients under stable therapy show lower
      health costs than those who need upward titration, switching or augmentation
      strategies. It is necessary to conduct randomized naturalistic studies to confirm
      these results.

PMID- 10079557
TI  - [An analysis of the demand for laboratory tests from primary care in a health
      area].
AB  - OBJECTIVE: To quantify the primary care demand for laboratory tests in a health
      area and to evaluate the variations in use in relation to the characteristics of
      the doctors, of organisation and of the population seen. DESIGN: Crossover.
      SETTING: A health area in the Community of Valencia with 110125 inhabitants.
      PARTICIPANTS: 89 primary care doctors from the area, with 8612 requests for lab.
      tests over 12 weeks. MEASUREMENTS AND MAIN RESULTS: All the lab. requests,
      including determinations (67730), diagnoses, and age and sex of patients, were
      recorded. Total and health consultations were calculated. The overall demand rate
      was 356 requests per 1000 inhabitants, with variations in the standardised rates
      by age of population between Districts (ranging from 242 to 548 per 1000). Lab.
      tests were requested for 8.6 of every 100 health consultations, with variations
      of up to three times this number depending on the distance from the laboratory.
      Women doctors asked for a higher number of determinations per request. whereas
      more requests were made for male than for female patients. CONCLUSIONS: There are
      substantial variations in primary care use of the laboratory, which are hard to
      explain by differences in underlying pathology. Some reasons for variation are
      organisational, but others remain to be tested. Findings indicate that
      interventions should be designed to improve the quality of laboratory use.
      Meanwhile, study of the causes of variations in demand continues.

PMID- 10079558
TI  - [The factors related to eating behaviors in a juvenile urban population].
AB  - OBJECTIVE: To find certain personal and social factors relating to the attitudes
      to food and the nutritional habits of young people. DESIGN: Observational,
      crossover study with randomised distribution. SETTING: Txantrea, a quarter of
      Pamplona with 20,578 inhabitants and with 1739 14 to 19-year olds in school.
      PARTICIPANTS: Sample of 465 people between 14 and 19, randomised and stratified
      for age. RESULTS: Under the life-style heading, 69% (64.3-73) tried to eat a
      varied diet; 56% (51.3-60.5) took part in the choice of family meals; and 52%
      (47, 3-56.3) ate snacks. On personal questions, 67% (62.3-71.1) said they had
      quite a lot or a lot of interest in diet; 50% (45.3-54.5) said they were quite
      concerned or very concerned about their diet; 22% (18.3-25.9) thought themselves
      obese or slightly obese, whereas 8% (5.7-10.9) were in fact obese. 71% (66.7
      74.9) were satisfied with their physique. 28% (24.1-32.2) had been on a diet. 81%
      (76.7-84.6) thought that young people gave a lot or quite a lot of importance to
      their physique. 78% (73.9-81.4) thought that the communication media had a lot or
      quite a lot of influence on the life-styles of young people. On education and
      information, 33% (28.7-37.3) thought they were well-informed on dietary
      questions, basically by the family. 38% (33.5-42.3) thought they were good or
      very good at cooking. 58% (53.3-62.3) said they were available for training in
      nutrition. The people with more interest in nutritional questions were more
      concerned and better informed. Being female was associated with: more interest
      and concern, having followed a diet, the view that the media had a big influence,
      feeling pressured by the family to eat more and availability for education. Being
      male was associated with: satisfaction with their physique, and thinking they
      were very thin, thin or balanced. CONCLUSIONS: Critical attitudes to the
      influence of the media were seen. There was a lot of concern about, and interest,
      in, nutrition. There was also quite a lot of not very healthy behaviour.

PMID- 10079559
TI  - [The breakfast patterns of adolescents: a comparison of the results obtained with
      a structured 24-hour diary versus a nonstructured one].

PMID- 10079560
TI  - [The databases of the National Library of Medicine of the United States].

PMID- 10079561
TI  - [The pocket Doppler: careful with complex examinations that are performed with
      simple apparatus!].

PMID- 10079562
TI  - [An outbreak of n-hexane-induced polyneuritis in a footwear factory].

PMID- 10079563
TI  - [The prevalence of oral mucosal changes in patients in primary dental care].

PMID- 10079564
TI  - [An extrapyramidal syndrome due to clebopride].

PMID- 10079565
TI  - [Are we calculating morphine consumption accurately?].

PMID- 10079566
TI  - We need to talk about head and neck cancer datasets.

PMID- 10079567
TI  - Carbamazepine monitoring.

PMID- 10079568
TI  - Poor prosthetics in UK dentistry.

PMID- 10079569
TI  - Patient anxiety levels.

PMID- 10079570
TI  - Media exposure of under-diagnosis.

PMID- 10079571
TI  - Suggested reforms.

PMID- 10079572
TI  - Harmony in primary care.

PMID- 10079573
TI  - A clinical guide to the endodontic treatment of non-vital immature permanent
      teeth.
AB  - A meticulous clinical technique is required for the successful endodontic
      treatment of non-vital immature permanent incisors. This paper describes the
      clinical procedures used to produce a hard tissue barrier in the open apex
      against which a gutta percha and zinc oxide-eugenol root filling is condensed.

PMID- 10079575
TI  - Tooth surface loss: an overview.

PMID- 10079576
TI  - Medical emergencies in general dental practice in Great Britain. Part 1: Their
      prevalence over a 10-year period.
AB  - OBJECTIVE: To assess the prevalence, nature and outcome of medical emergencies
      experienced by general dental practitioners (GDPs) over a 10-year period. DESIGN:
      Postal questionnaire survey of a random sample of GDPs in Great Britain.
      SUBJECTS: 1500 GDPs, 1000 in England & Wales and 500 in Scotland. RESULTS: There
      was a 74% response. Emergency events were reported by 70.2%: the number reported
      by a single individual ranged from none to 33. The most commonly experienced
      events, including those associated with general anaesthesia, were (as a
      percentage of the total) for England & Wales and Scotland, respectively: fits and
      seizures (31.0%, 36.3%); swallowed foreign bodies (15.7%, 18.1%); attacks of
      asthma (13.8%, 11.1%); chest pain associated with angina pectoris (10.1%, 11.0%)
      and diabetic events (10.6%, 9.0%): none of these resulted in any serious
      sequelae. More events were reported in Scotland. Overall, there were 20 deaths
      resulting from medical emergencies reported in the survey, 4 affecting passers-by
      and none associated with general anaesthesia. 8849 years of practice experience
      were represented (by 94% of respondents), from which an estimate of the frequency
      of events was made. CONCLUSIONS: An emergency event was reported, on average, for
      every 4.5 practice years in England & Wales and 3.6 years in Scotland and death
      associated with general dental practice, on average, once in 758 and 464 years,
      respectively.

PMID- 10079577
TI  - Patient expectations of oral implant-retained prostheses in a UK dental hospital.
AB  - STATEMENT OF PROBLEM: The loss of the natural dentition leads to severe
      functional impairment in many edentulous adults. A prosthesis retained and
      supported by osseointegrated dental implants may provide a satisfactory solution
      for people who have lost all their natural teeth. However, little information is
      available as to what patients requesting implants expect of implant-retained
      prostheses. AIM: The aim of this study was to assess the expectations of a group
      of edentulous patients requesting implant therapy. METHOD: The study included two
      groups: (1) a group of edentulous adults who requested implant therapy ('implant
      group'); and (2) an edentulous control group, of similar age and gender
      distribution as the implant group, receiving conventional complete dentures.
      Following a clinical and radiographic examination of the patients, data were
      collected using validated questionnaires. Both groups made a subjective
      assessment of current dentures. The implant group also completed a questionnaire
      which assessed expectations of implant-retained prostheses. RESULTS: Baseline
      satisfaction with current dentures was low in both groups, with the implant group
      being significantly less satisfied with comfort and stability of their mandibular
      dentures. Perceived ability of the implant group to chew hard foods was less than
      the control group. The implant group's expectations of an implant-retained
      prosthesis were significantly greater than for a conventional denture.
      CONCLUSION: Careful assessment of patient expectation of implant therapy is
      essential to determine appropriate treatment need, and to highlight unrealistic
      expectations.

PMID- 10079578
TI  - Dental technician education and training--a survey.
AB  - As the Dental Auxiliaries Review Group report continues in the consultation
      stage, the dentist needs to keep up-to-date on all aspects of auxiliary career
      developments. Dental technician education and training has changed radically
      during the past 25 years as shown by three surveys--the latest carried out during
      1998 and reported in this paper. As leader of the dental team, the dentist needs
      to be aware of these changes in order to make an informed contribution to the
      debate.

PMID- 10079579
TI  - Preventing pneumococcal disease: a Canadian consensus conference. 16-18 February
      1998.

PMID- 10079580
TI  - Respiratory virus surveillance. FluWatch Project.

PMID- 10079581
TI  - Thalidomide's tightly controlled "comeback".
AB  - Thalidomide has anti-inflammatory properties and shows promise for treating a
      variety of infectious and autoimmune diseases, but it must be used with strict
      precautions.

PMID- 10079582
TI  - Managing year 2000 (Y2K) compliance in the medical practice.
AB  - It is the responsibility of every medical practice to examine the year 2000
      compliance of all medical devices, facilities, and computer systems that it uses,
      and whether external business partners are also taking appropriate steps in this
      area. You need a plan, and you need to start right now.

PMID- 10079583
TI  - Beta 2-microglobulin amyloidosis in renal failure: understanding this recently
      recognized condition.
AB  - Beta 2-microglobulin amyloidosis can cause significant suffering in patients with
      chronic renal failure. Although renal transplantation is currently the only
      treatment, medical and surgical therapies may decrease pain and disability.

PMID- 10079584
TI  - A 47-year-old man with headache and ptosis.

PMID- 10079585
TI  - Carpal tunnel syndrome: the cause dictates the treatment.
AB  - Mild carpal tunnel syndrome should be conservatively treated and severe carpal
      tunnel syndrome usually requires surgery; however, management of moderate carpal
      tunnel syndrome is more complex. Usually, the treatment is dictated by the cause,
      which may be occupational injury, acute trauma, systemic diseases such as
      diabetes, hypothyroidism, or rheumatoid arthritis, or other causes.

PMID- 10079586
TI  - Multicentric reticulohistiocytosis: a mimic of gout and rheumatoid arthritis.
AB  - Multicentric reticulohistiocytosis is a rare cutaneous-articular disease that may
      mimic more common disorders such as rheumatoid arthritis or tophaceous gout. In
      one fourth of patients, it is a paraneoplastic process. This brief overview is
      aimed at physicians who care for patients with polyarthritis, to alert them to
      distinctive features that differentiate multicentric reticulohistiocytosis from
      the common arthritides.

PMID- 10079587
TI  - Evolving concepts in the management of patients with neutropenia and fever.
AB  - Much has changed in the treatment of patients with fever and neutropenia,
      including the patterns of microbial flora and drug resistance and the drugs used.
      More patients now have indwelling central venous catheters, exposing them to new
      types of infections. This article reviews the recent treatment guidelines
      published by the Infectious Diseases Society of America.

PMID- 10079588
TI  - Falls in the elderly: office-based evaluation, prevention, and treatment.
AB  - Falls are serious and relatively common, and can result in significant morbidity
      and mortality for older adults. The office evaluation should focus on detecting
      underlying risk factors, adjusting high-risk medications, modifying unsafe
      behaviors, assessing home safety, and referring for physical therapy. Recent
      randomized trials have demonstrated successful interventions to decrease falls.

PMID- 10079589
TI  - Two teenagers die in outbreak of meningococcal disease in Rotherham.

PMID- 10079591
TI  - Influenza activity starts while Christmas interrupts surveillance.

PMID- 10079592
TI  - An overview of cerebral aneurysms. Which factors affect the outcome of
      microsurgical treatment.
AB  - There is a higher incidence of subarachnoid hemorrhage (SAH) with advancing age.
      Considerable controversy exists as to whether aggressive therapy is indicated in
      the elderly. With increased life expectancy, a greater number of elderly patients
      with SAH will require treatment in the future. This study was undertaken to
      evaluate the effect of age, aneurysm characteristics, Hunt-Hess grade on
      admission, race, and smoking status to the eventual outcome. The results of 76
      consecutive aneurysms clipped in 67 patients by a single surgeon (B.B.) were
      analyzed. Among the variables, Hunt-Hess grade at admission seemed to be the only
      significant factor influencing the outcome in this series (X2MH = 17.136, p <
      0.001). Advancing age did not worsen the prognosis after SAH and therefore age
      should not be a contraindication for aggressive management.

PMID- 10079593
TI  - Summary of the 1998 annual meeting's scientific sessions.

PMID- 10079594
TI  - Stroke: no more diagnose and adios.

PMID- 10079595
TI  - Stroke.

PMID- 10079596
TI  - Christos Stavros Papastavros, M.D.

PMID- 10079597
TI  - Looking backward on two lives in medicine.

PMID- 10079598
TI  - Annual Conference of Polish Association of Neuropathologists on "Encephalitides",
      Warszawa, May 23, 1998.

PMID- 10079599
TI  - The history of studies on subacute sclerosing panencephalitis in Poland.
AB  - The main trends are described in the studies of subacute sclerosing
      panencephalitis conducted in Poland or abroad with participation of Polish
      scientists. The history of these studies began in the years 1957-1959 with the
      works of Wender and Osetowska and ends presently at the end of our century with
      extinction of SSPE as a result of consistently conducted obligatory vaccinations
      against measles. The studies of Polish authors involved the problems of clinical
      diagnosis using immunological, electrophysiological and neurological imaging
      methods. Neuropathological problems were also studied extensively. Parallely with
      similar studies in the foremost foreign centres trials of SSPE treatment were
      undertaken in Poland, in recent years by means of intracerebroventricular
      administration of interferons. An original Polish method was the treatment with
      inducers of endogenous interferons. After the introduction of vaccinations
      against measles epidemiological studies repeated in the whole country were
      introduced for the assessment of the results of this preventive measure. These
      studies are regarded as model ones at international level.

PMID- 10079600
TI  - Some aspects of the inflammatory process.
AB  - The inflammatory process is a nonspecific complex, stereotype, coordinated
      response of tissues to injury. This process involves vascular permeability,
      active migration of blood cells, and passage of plasma constituents into the
      injurious tissue. The molecules that mediate the initial events of inflammation
      are the adhesion molecules. They are localized on leukocytes and endothelium. The
      adhesion and cell-cell cooperation appear to be critical for the migration of
      leukocytes to the abluminal surface of the blood vessels. The emigrating cells
      initiate the complex reactions that are controlled by a multitude of
      intercellular messengers called mediators. Prostanoids, that are products of
      arachidonic acid metabolism in cyclooxygenase pathway are involved in the process
      of communication between cells. Two isoforms of the cyclooxygenase COX-1 and COX
      2 were found. They subserve different physiological function largely because of
      the striking differences in their tissue expression and regulation. A common
      feature of chronic inflammation is the persistence of a large number of
      leukocytes in the tissue; thus, their removal is important for the resolution of
      the inflammatory process. The mechanism by which they are removed includes the
      apoptotic recognition system. The new concepts regarding the therapy of the
      diseases concomitant with inflammatory reaction should include the inhibition of
      the appropriate isoform of cyclooxygenase and the regulation of apoptotic process
      in some cells.

PMID- 10079601
TI  - The morphological picture of developing meningo-encephalitis in central nervous
      system.
AB  - In this paper we are summarizing our observations collected during several years
      and concerning the inflammatory changes in maturing human brains. Studies of
      inflammatory reactions in developing central nervous system (CNS) revealed that
      their morphological picture changes along with the maturation of the brain and
      formation of fetal immune response. We have analyzed various types of
      inflammatory processes (meningeal infiltrations, meningoencephalitis with
      perivascular infiltrates and glial interstitial changes, inflammatory-necrotic
      lesions) occurring in different stages of brain development. In all these
      processes gradual maturation of cell lines belonging to the immune system was
      seen. Evident correlation between tissue inflammatory reaction and necrosis was
      confirmed. The necrotic changes mainly within hemispheric white matter may result
      in the cortical malformations. The morphologic manifestation of inflammation in
      the developing CNS is dependent on the stage of maturation of the brain structure
      and immunological response.

PMID- 10079602
TI  - HIV-1-infection in the CNS. A pathogenesis of some neurological syndromes in the
      light of recent investigations.
AB  - The main factors in the pathogenesis of AIDS-dementia complex (ADC) are analyzed.
      The author suggests that these factors can be divided into two groups. The
      "nonspecific" factors present in every immunologic processes manifested by
      inflammation compose the first group. They are cytotoxic lymphocytes T, the
      immunoactivation of infected macrophages, cytokines, NO, NOS and iNOS, the
      increase of the BBB permeability, the accumulation of beta-amyloid precursor
      protein, excitotoxic amino acids, various and numerous cells adhesion molecules.
      The second group may contain factors connected with HIV-1 infection of CNS. In
      the pathogenesis of AIDS an important role is played by toxic glycoproteins gp
      120 and gp 41 which are in the coat of HIV-1 virus, nucleotide sequences
      variability, possibility of various virus replication in various parts of CNS,
      the participation of lymphokines IL-4 and IL-10, and presence of co-receptors to
      HIV-1 virus on lymphocytes, macrophages, neurons and microglial cells.

PMID- 10079603
TI  - A case of the subacute brainstem encephalitis.
AB  - A case of brainstem encephalitis of undetermined etiology is reported in 66-year
      old woman who had a sudden onset of illness with left abducens palsy, nystagmus
      and ataxia. The symptoms progressed to complete paralysis of eye movements,
      dysphagia and left hemiparesis with generalized hyperreflexia. Examination of
      CSF, CT scan and MRI of the brain were normal. The patient died 4 months after
      onset of disease. Neuropathologic study disclosed in the brainstem numerous
      perivascular and nodular inflammatory cell infiltrations composed predominantly
      of lymphocytes T and B. Most intensive inflammation concerned midbrain and
      pontine tegmentum and to a lesser degree medulla oblongata, pontine nuclei and
      cerebellar nuclei. Basal ganglia, cerebral and cerebellar cortex were unaffected.
      Neuropathological finding was reminiscent of brainstem encephalitides related to
      viral infection or to paraneoplastic syndrome. However, HSV-1, EBV, and CMV
      antigens were not detected by immunohistochemistry, as well as evidences of
      malignancy were not present in this case.

PMID- 10079604
TI  - Acute hemorrhagic encephalitis (Hurst disease) associated with neuroaxonal
      dystrophy.
AB  - Two cases that fulfil the clinical and neuropathological criteria of acute
      hemorrhagic encephalitis are described. Histological examination revealed
      additionally focal changes in the white matter characteristic for neuroaxonal
      dystrophy. The differences in the clinical course and morphological picture
      observed in both cases are discussed.

PMID- 10079605
TI  - Atypical case of sporadic Creutzfeldt-Jakob disease (CJD) in a young adult.
AB  - The great concern exists that new variant of CJD (nvCJD) developed as a result of
      exposure to bovine spongiform encephalopathy (BSE)-infected meat products.
      Therefore, all cases of CJD in the young, as the one of ours are the matter of
      interest. The 21-year-old female developed a rapid progression of pyramidal,
      extrapyramidal and cerebellar signs, visual loss and psychiatric symptoms,
      leading to death in 16 weeks. The microscopic features were: a neuronal loss
      accentuated in cerebral cortex with extensive astroglia proliferation and
      spongiform changes. Immunohistochemical staining, revealed the presence of
      "synaptic" deposits of PrP in the cerebral cortex and in the cerebellum. No
      florid amyloid plaques were present. The case was diagnosed as a sporadic CJD,
      with some features of Heidenhein variant (visual symptoms) and
      corticostriatocerebellar category. The pathological findings excluded a nv CJD
      which is linked with BSE.

PMID- 10079606
TI  - Progressive multifocal leukoencephalopathy (PML) and cerebral toxoplasmosis in an
      adult patient, with no symptoms of underlying immunosuppressing illness.
AB  - We present a case of the coincidence of progressive multifocal
      leukoencephalopathy (PML) and central nervous system (CNS) toxoplasmosis in an
      adult patient, without a detectable cause of cell-mediated immunity impairment.
      The proper diagnosis was made postmortem on the basis of histological changes
      typical of both pathological processes. PML was characterized by the presence of
      subcortical focal demyelination, containing enlarged, densely basophilic
      oligodendrocyte nuclei, often with intranuclear inclusion, and bizarre
      astrocytes, mimicking neoplastic cells. PML was confirmed by detecting numerous
      papova virus particles in oligo- and astroglial nuclei by thin-section electron
      microscopy. Cerebral toxoplasmosis was characterized by the presence of multiple
      well-circumscribed necrotizing abscesses. Numerous Toxoplasma gondii (T. gondii)
      cysts and free, non-encysted protozoan parasites were found among the
      inflammatory infiltrates. The diagnosis of cerebral toxoplasmosis was further
      confirmed by immunocytochemistry. In order to detect putative immunosuppressive
      background underlying both pathological processes, HIV infection was taken into
      consideration, however, no histopathological changes indicative of AIDS either in
      the CNS or in the peripheral organs were eventually found. Moreover no HIV
      provirus genome was identified in the formalin-fixed, paraffin embedded brain
      tissue by the polymerase chain reaction (PCR). Current view on the selected
      aspects of the pathogenesis of both disorders were discussed.

PMID- 10079607
TI  - Vascular changes in tuberculous meningoencephalitis.
AB  - Our report refers two cases of tuberculous encephalomeningitis which differ in
      the course and pathological changes. In case 1 blood vessels showed features of
      peri, endo-, or panvasculites. In some vessels endothelium proliferation leading
      to the stenosis or obliteration of the vascular lumen was observed. Necrosis was
      an effect of vessels occlusion. In case 2 many fewer vessel were involved in
      onflammation process. Vascular changes were also less extensive and were observed
      more rarely. Tuberculous infection often caused less tissue lesions than vascular
      changes. Different pathological changes probably depend on the type and virulence
      of Myobacterium tuberculosis and on the host immune response to the infection.

PMID- 10079608
TI  - Multilocular cysticeral and hydatid cysts of the brain: a report of three cases.
AB  - Three cases of multilocular parasitic brain cysts are presented; two cases of
      specific form of neurocysticercosis and one case of multilocular hydatid cyst.
      MRI shows features seen in other cystic lesions of the CNS. In all cases the
      diagnosis was established by neurosurgical brain biopsy. The authors indicate
      that the parasitic disease should be taken into consideration in differential
      diagnosis of tumor-like cystic brain lesions.

PMID- 10079609
TI  - Ultrastructural changes in the central and peripheral nervous system in the rat
      with experimental allergic encephalomyelitis.
AB  - The aim of the study was the evaluation of ultrastructural changes in rats
      central and peripheral nervous system after the introduction of experimental
      allergic encephalomyelitis (EAE) and after the treatment with spinal cord protein
      hydrolysate. Reduced structural disturbances in myelin were found after oral
      treatment with hydrolysate. In addition, the indications of remyelinization
      processes have been observed.

PMID- 10079610
TI  - Phenotype of mast cells in the congenital malformations of human cerebrovascular
      system.

PMID- 10079611
TI  - Antibiotics and sacred cows.

PMID- 10079612
TI  - Direct reimbursement.

PMID- 10079613
TI  - The safety of dental composite biomaterials.

PMID- 10079614
TI  - Quality assurance in the dental profession.

PMID- 10079615
TI  - Fee guides.

PMID- 10079616
TI  - Making informed decisions.

PMID- 10079617
TI  - Back to basics: making a vacuum-formed, custom-fitted intraoral mouthguard using
      the "dry model" technique.
AB  - For a mouthguard to function properly, it must fit well. It is possible to
      produce a well-fitting mouthguard using the "dry model" technique, which is
      relatively inexpensive and easy to learn. Custom-fitted intraoral mouthguards
      help prevent or reduce the severity of concussions as well as minimize oral
      cavity injuries.

PMID- 10079618
TI  - Infective endocarditis and dentistry: outcome-based research.
AB  - Antibiotic prophylaxis for prevention of infective endocarditis has long been
      recommended for patients receiving dental care. Two studies of patients with
      endocarditis found limited risk associated with dental treatment. It is
      imperative that guidelines for therapy be based on outcome studies and on
      evidence of safety, efficacy and cost effectiveness.

PMID- 10079619
TI  - Continuing water fluoridation in the City of Calgary, Alberta, 1997-1998.
AB  - The issue of water fluoridation has a long history in the City of Calgary
      (population 820,000). There were five plebiscites before 1998, with only the 1989
      plebiscite receiving a majority vote in favour of fluoridation. Calgary
      introduced water fluoridation in 1991. In the fall of 1997, the City sponsored a
      review of water fluoridation as a public policy based on information provided by
      a group of concerned citizens. An expert panel was formed to look at the new
      scientific information on the subject; four of the five members agreed that there
      was not sufficient evidence upon which to make substantial changes to the water
      fluoridation policy. Nevertheless, the City's Standing Policy Committee on
      Operations and Environment recommended that a plebiscite on water fluoridation be
      held in conjunction with the 1998 municipal election. This decision was
      ultimately supported by City Council. Under the direction of the Calgary Regional
      Health Authority, the Fluoride Education Steering Committee undertook three
      strategies for the campaign: building partnerships, educating health
      professionals and educating the public. In spite of the anti-fluoridation
      activities, Calgarians voted 55 per cent in favour of continuing fluoridation of
      the municipal water supply.

PMID- 10079620
TI  - The development of ISO 9002 quality management standards for Canadian dental
      practices.
AB  - The department of dentistry of the Hospital for Sick Children has actively
      maintained a quality assurance system since the early 1980s. In addition, members
      of the department have taught courses and published articles on risk management
      and quality assurance for over a decade. The decision to achieve ISO 9002
      registration led to an intensive 10-month process to adapt ISO systems and
      standards to Canadian institutional dental practice. This article describes the
      ISO registration system and the changes required for an existing quality
      assurance program to conform to ISO standards.

PMID- 10079621
TI  - Porcelain veneers: a challenging case.
AB  - A patient in his early 20s with teeth badly discoloured by tetracycline was
      seeking treatment to improve his esthetics. Because retreatment and cost were
      important considerations, porcelain veneers were the treatment of choice. The
      challenge in this case was to mask the underlying tetracycline stain before the
      final cementation and thus gain more control over the final shade of the veneers.

PMID- 10079622
TI  - Maximising the fracture resistance of dentine-bonded all-ceramic crowns.
AB  - Results of previous studies have indicated that the use of different ceramic
      materials and differing bonding/luting systems may affect resistance to fracture
      of teeth restored with dentine-bonded crowns. It is the purpose of this
      investigation to examine in vitro fracture resistance of dentine-bonded ceramic
      crowns, using materials in combination which have demonstrated increased fracture
      resistance when they are used individually. Ten sound maxillary premolar teeth
      were selected. These teeth were prepared for full crowns in a similar manner to
      previous, related studies. Standardised crowns were constructed in a leucite
      reinforced ceramic (Empress: Ivoclar-Vivadent, Liechten-stein) and placed using a
      dentine-bonding system and resin-composite luting system (3M; St. Paul, MN, USA).
      Compressive force was applied through a 4 mm diameter steel bar applied to the
      occlusal surface of the restored specimens. A mean fracturing force of 1.67 kN
      was recorded, statistical analysis indicating that this was significantly greater
      than any previously used combination of ceramic material and bonding/luting
      system, and greater than a group of sound, unrestored teeth. The fracture
      resistance of teeth restored in vitro by dentine bonded crowns may be enhanced by
      the combination of the materials described.

PMID- 10079623
TI  - Crack formation of all-ceramic crowns dependent on different core build-up and
      luting materials.
AB  - OBJECTIVES: The aim of this in vitro study was to evaluate various core build-up
      and luting materials regarding their effect on crack formation of all-ceramic
      crowns. METHODS: Fifty-six freshly extracted sound human third molars were
      prepared according to a standardized procedure obtaining a circular shoulder of
      1.5 mm with all margins located in dentin. Sixty percent of the dentin volume
      were removed and restored with totally bonded build-up composite resins or resin
      modified glass ionomer cements (RMGIC) or compomers. Cast IPS-Empress caps were
      manufactured and luted with the different materials. For each material group, the
      volumes of the core build-ups and of the luting cements were determined. The caps
      were examined for cracks after 1, 3, 6, 9 and 12 months storage in 0.9% saline
      solution at 37 degrees C. RESULTS: The tested groups revealed no major
      differences in the percentage of the core build-ups and in the volume of the
      luting cements. After 12 months only the group with composite resin build-up and
      luting showed no crack formation. RMGIC/compomer build-up or RMGIC/compomer
      luting always resulted in cracking of the caps. CONCLUSIONS: Within the limits of
      this study it can be concluded that the hygroscopic expansion of RMGIC/compomer
      materials led to failure of all-ceramic crowns, when the materials are used for
      both core build-up or adhesive bonding.

PMID- 10079624
TI  - The biaxial flexural strength of two pressable ceramic systems.
AB  - The biaxial flexural strength of Optimal pressable ceramics and IPS Empress
      pressable ceramics were tested, compared and the micro-structures and
      compositions explored. The materials evaluated were Optimal shaded (Opcs) and
      unshaded (Opcus) ceramics and IPS Empress shaded (Ems) and unshaded (Emus)
      ceramics. Twenty-one disc specimens per material were prepared, heat-treated and
      tested. The piston on three-ball test ASTM F394-78 (1991) was used to test the
      specimens in a universal testing machine at a crosshead speed of 0.15 mm/min.
      Specimens were viewed in a scanning electron microscope and X-ray diffraction
      used to determine the phases present. Mean strengths (MPa +/- SD) were: Ems 120.1
      +/- 20.5, Emus 135.8 +/- 16.0, Opcs 139.1 +/- 14.3 and Opcus 138.0 +/- 11.5.
      There was no statistically significant difference between Optimal shaded, Optimal
      unshaded and Empress unshaded strength values (p > 0.05). Empress shaded strength
      values were significantly lower than the other materials tested (p < 0.05).
      Weibull analysis provided m values: Ems 6.1, Emus 10.2, Opcs 12.8 and Opcus 13.9
      and 1% and 5% probabilities of failure. Secondary electron imaging revealed a
      dense dispersal of leucite crystals in the glassy matrix of the Optimal ceramics
      of an average size 5.5 +/- 9.7 micron 2 for the Optimal shaded ceramic and 6.6 +/
      13.3 micron 2 for the Optimal unshaded ceramic. Leucite crystal agglomerates
      were evident for the Empress shaded material and a uniform distribution of fine
      leucite crystals (1.9 +/- 1.8 micron 2) for the Empress unshaded ceramic. Crystal
      and matrix microcracking were present in most of the material microstructures,
      together with porosity and tabular alumina platelets in the Optimal ceramics. X
      ray diffraction revealed the presence of tetragonal leucite and small amounts of
      cubic leucite. Optimal ceramics and Empress unshaded ceramic provided higher
      strength and Weibull m values compared with Empress shaded ceramic. Inherent
      material defects were characterised and cubic leucite was identified.

PMID- 10079625
TI  - Mechanical properties of an experimental denture soft lining material.
AB  - OBJECTIVES: The objective of the present study was to evaluate the mechanical
      properties of an experimental formulation (Exp. 1) in order to assess its
      potential as a denture soft lining material. The same properties of a popular
      commercially available denture soft lining material (Molloplast-B) were
      determined and compared with the properties of Exp. 1. METHODS: Exp. 1 specimens
      were obtained by curing for 24 h at room temperature after the addition of the
      appropriate amounts of catalyst and cross-linker. Molloplast-B specimens were
      obtained after curing according to the manufacturer's instructions. The
      properties measured in the study were hardness, tear resistance, tensile strength
      and the bond strength of the material to a heat-cured acrylic denture base
      material. RESULTS: Exp. 1 had a significantly greater tensile strength, percent
      elongation, tear resistance and peel strength (p < 0.0001) than Molloplast-B.
      There was no significant difference in the hardness values of the two materials,
      although Molloplast-B had a significantly higher tensile bond and shear bond
      strength (p < 0.05). CONCLUSIONS: It was concluded that there was no significant
      difference in the hardness of Exp. 1 and Molloplast-B. Exp. 1 had superior
      tensile and tear properties. Its peel bond strength was superior to that of
      Molloplast-B, although its tensile bond strength and shear bond strength were
      less.

PMID- 10079626
TI  - Influence of self-etching primer drying time on enamel bond strength of resin
      composites.
AB  - OBJECTIVES: In clinical situations, a dentine primer is usually applied to
      enamel, in addition to dentine. This study was carried out to determine the
      influence of the air drying time of self-etching primers on their bond strength
      to enamel. METHODS: Three self-etching primer systems, Fluoro Bond (FB, Shofu
      Inc.), Liner Bond II (LB, Kuraray Co.) and Mac Bond 2 (MB, Tokuyama Co.) were
      employed. Bovine mandibular incisors were mounted in self-curing resin and the
      enamel surfaces were wet ground with number 600 SiC paper. Following primer
      application, the enamel surface was dried with compressed air for 0, 2, 5, 10,
      20, and 30 s from 10 cm above the enamel surface using a three-way syringe.
      Adhesives were applied and composites were condensed into a Teflon mold (4 x 2
      mm) placed on the enamel and light activated. Ten samples per test group were
      stored in 37 degrees C water for 24 h, then shear tested at a crosshead speed of
      1.0 mm min-1. One-way ANOVAs followed by Duncan tests (p < 0.05) were done.
      RESULTS: The enamel bond strengths varied with the different air drying times and
      ranged from 8.2 +/- 3.2-17.4 +/- 3.0 MPa for LB, 10.9 +/- 2.8-16.3 +/- 3.3 MPa
      for FB, and 17.5 +/- 2.5-19.4 +/- 2.2 MPa for MB. For LB and FB, there appeared
      to be a minimum drying time of 10 s. LB was the most affected by drying time,
      while MB did not change. CONCLUSIONS: The data suggests that the enamel bond
      strengths of these bonding systems can be influenced by the drying time of the
      primer applied prior to bond agent application and the tendency was different
      among the systems studied.

PMID- 10079627
TI  - Effect of water content on the physical properties of model dentine primer and
      bonding resins.
AB  - OBJECTIVE: Primers and adhesives containing hydroxyethyl methacrylate (HEMA) are
      placed on moist dentine even though several studies indicate that water may
      interfere with the polymerization reaction. The purpose of this study was to
      evaluate the influence of increasing amounts of water on the physical properties
      of a model dentine primer resin (HEMA) and model dentine bonding resin (a mixture
      of HEMA and Bis-GMA). METHODS: Miniature (ca 10 x 0.5 mm (long x thick) hour
      glass shaped and parallel-sided specimens were created by casting the monomer or
      comonomer mixtures into appropriately shaped moulds. The water content was either
      0, 5, 9, 17 or 29 vol%. One hour after polymerization, half the specimens were
      subjected to physical testing under dry conditions. The other half were immersed
      in water for 24 h and then tested while wet. The ultimate tensile strength (UTS),
      modulus of elasticity (E), percent elongation at failure, and toughness were
      calculated. RESULTS: The properties of the dry-stored primer and bonding resins
      were not altered by water incorporation up to 9 vol%. Higher water content
      lowered the physical properties (P < 0.05). Immersion of primers polymers in
      water for 24 h significantly decreased their properties. Water immersion of the
      bonding resins was unaffected only for specimens containing 0 or 5 vol% water.
      CONCLUSIONS: The plasticizing effects of extrinsic water are far more important
      than the effects of intrinsic water in poly-HEMA resin. Hybrid layers composed
      primarily of poly-HEMA would be expected to be more elastic than those made with
      bifunctional, cross-linked polymer chains.

PMID- 10079628
TI  - Comparison of the bond compatibility of titanium and an NiCr alloy to dental
      porcelain.
AB  - OBJECTIVES: The aim of this study was to investigate the bond compatibility
      between porcelain and titanium, by using three-point bending, oxide adherence and
      thermal expansion tests, and to compare the results with those of a conventional
      NiCr alloy-porcelain system. METHODS: The three-point bending test was used and
      the results were evaluated according to DIN draft 13927. Fractured surfaces of
      the metal and porcelain were examined macroscopically. The oxide adherence test
      was applied to titanium and NiCr alloy with appropriate oxidation degrees. After
      an oxide film was formed on the specimens, tensile strength test was applied.
      Oxide adherence strength values were set and fractured surfaces were examined
      macroscopically. In the thermal expansion test, thermal expansion curves and
      thermal expansion coefficients of titanium, NiCr alloy and tested porcelains were
      determined. Differences in thermal expansion values (delta alpha) in all metal
      porcelain pairs were calculated to allow inferences to be made about residual
      stress levels. RESULTS: The bending strengths of all groups were found to be
      within the acceptable standard levels. At the end of the oxide adherence test,
      the results indicated that the adherence of the formed oxides to the metals were
      at a desired level. As a result of the thermal expansion test, the titanium
      porcelain and NiCr-porcelain systems showed compressive thermal stress. However,
      the titanium-porcelain pair exhibited large positive delta alpha values. This
      results is found to be above the proposed thermal compatibility. CONCLUSIONS: It
      was concluded that the bond compatibility between titanium and porcelain was
      comparable with the NiCr-porcelain system.

PMID- 10079629
TI  - A fluid filtration and clearing technique to assess microleakage associated with
      three dentine bonding systems.
AB  - OBJECTIVES: The aims of this in vitro study were to (a) measure fluid flow
      through teeth restored with one of three dentine bonding systems and a resin
      composite restoration; (b) measure the distribution of a silver tracer through
      the same teeth, and make a comparison with fluid flow; and (c) investigate the
      effect of thermocycling on both measurement types. METHODS: Coronal segments of
      30 premolars, randomly allocated to three equal groups, were assessed by fluid
      filtration. Each group was restored with a resin composite restoration in
      conjunction with Fuji Bond LC (FBLC), Scotchbond Multi-Purpose Plus (SMP+) or
      Prime&Bond 2.1 (P&B2.1). Fluid filtration rates were measured in the intact crown
      and then after cavity preparation, conditioning, dentine bonding, restoration and
      at 2 and 24 h, 1 week and 1 month following restoration. Six specimens from each
      group were thermocycled at 1 week. After final filtration measurements the
      specimens were perfused with silver nitrate and cleared before scoring tracer
      penetration. RESULTS: No significant differences (P > 0.05) in fluid filtration
      rates were found amongst the different bonding systems or at any restoration
      stage. Thermocycling was not associated with any significant (P > 0.05) increase
      in fluid filtration. Final fluid filtration and tracer distribution showed a weak
      and not statistically significant correlation (P > 0.05). The penetration of
      silver stain indicated a failure of the restorations to seal the cavity and
      demonstrated a possible pathway by which in vivo post-operative sensitivity could
      occur. CONCLUSIONS: Although not statistically significant, conditioning of the
      cavity increased the dentinal permeability but this effect was variable.
      Thermocycling had no statistically significant effect on microleakage.

PMID- 10079630
TI  - A survey of output intensity and potential for depth of cure among light-curing
      units in clinical use.
AB  - OBJECTIVES: The light intensity of curing lights used in private dental offices
      was measured using commercial curing and heat radiometers and related to
      uniformity of cure depth of standardized composite specimens. METHODS: The
      intensity of 130 curing light from 107 dental offices was measured with curing
      and heat radiometers. Due to analogue readings, results were recorded in steps of
      25 mW cm-2 and assigned a category number. A total of 50 lights were randomly
      selected to polymerize standardized 3 mm thick composite cylinders. The composite
      was irradiated for 50 s according to the manufacturer's instructions. The Knoop
      hardness value was measured at the top and bottom surfaces and the uniformity of
      cure depth was calculated from the ratio of these two values. RESULTS: Light
      intensity measured by the curing and heat radiometers was in the range of 25-825
      and 0-325 mW cm-2, respectively. Functions of maximum likelihood estimation of
      the top and bottom surface hardness were 57 N/N + 1.3 and 80 N/N + 17.7,
      respectively (N = light intensity category number). The relationship between the
      logarithmic transformation of the hardness ratio and light intensity was linear
      (R2 = 0.84 p < 0.001). CONCLUSION: According to the manufacturer, a curing light
      is considered as unsuitable for use with a reading of < 200 mW cm-2 by the curing
      radiometer and > 50 mW cm-2 by the heat radiometer. Applying these criteria to
      the present study, 46% of the lights (without repetitions) required repair or
      replacement. The strong correlation found between the hardness ratio and light
      intensity verifies the usefulness of the curing radiometer in predicting the
      polymerization ability of the light activation units.

PMID- 10079631
TI  - Patient discomfort and cross-infection control in bitewing examination with a
      storage phosphor plate and a CCD-based sensor.
AB  - OBJECTIVES: The aim was to compare a CCD-based sensor and a storage phosphor
      plate with respect to patient discomfort and the efficacy of a simple cross
      infection control procedure in connection with a posterior bitewing examination.
      METHODS: 130 patients accepted to have one posterior bitewing of the left and
      right side taken with two digital radiography systems, the Digora phosphor plate
      and the Trophy RVG XL, CCD-based sensor system. The patients assessed their
      feeling of discomfort after the examination on a 100-mm. Visual Analogue Scale
      (VAS). Microbiological samples were taken from the RVG sensor and cord and from
      the Digora envelope, plate and scanner during examination of 14 patients. The
      samples were plated and incubated anaerobically, and the colony-forming units
      counted. RESULTS: Median VAS score for discomfort was 20 min for Digora and 32
      min for the RVG sensor (P < 0.001). Median total counts of cultivable bacteria
      were low (< 20), the majority being catalase-positive, Gram-positive cocci and
      Gram-positive rods, presumably skin bacteria. Only the samples taken from the
      enveloped Digora plate and the rubber tube coated RVG sensor immediately after
      exposure yielded large numbers of oral bacteria. CONCLUSION: The phosphor plate
      was less unpleasant than the CCD sensor. Cross-contamination posed a minor
      problem for both systems when a simple, standard hygiene procedure was followed.

PMID- 10079632
TI  - The effectiveness of two sterilization methods when different precleaning
      techniques are employed.
AB  - The effectiveness was investigated of methods for the preparation of dental
      handpieces prior to sterilization procedures utilizing ethylene oxide (ETO) gas.
      The handpieces were cleaned using either a forced-air purging unit (group 1) or
      by flushing with air and water from the dental unit (group 2). They were
      inoculated with either Bacillus subtilis or Streptococcus mutans. After exposure
      to either steam or ETO gas, the handpieces were flushed with saline and the
      viability of recovered bacteria assessed. No viable bacteria were recovered from
      group 1 handpieces treated with either ETO gas or steam. However, viable S.
      mutans were recovered from group 2 handpieces following exposure to ETO gas.
      Thus, the use of a high-pressure forced-air purging unit may be required for the
      reliable sterilization of dental handpieces by ETO gas, as viable S. mutans could
      be recovered from untreated handpieces exposed to ETO gas.

PMID- 10079633
TI  - What? Use OMT in treating Parkinson's? ... never!

PMID- 10079634
TI  - What we have to be is what we are.

PMID- 10079635
TI  - Kevorkian kills patients along with the clinical research to help them.

PMID- 10079636
TI  - Time to tell the world about osteopathic medicine.

PMID- 10079637
TI  - Osteopathic profession needs leaders with progressive stance.

PMID- 10079638
TI  - Revisiting the role of osteopathic manipulation in primary care.

PMID- 10079639
TI  - Revisiting the role of osteopathic manipulation in primary care.

PMID- 10079640
TI  - Colposcopy may not be clinically relevant.

PMID- 10079641
TI  - Standard osteopathic manipulative treatment acutely improves gait performance in
      patients with Parkinson's disease.
AB  - Patients with Parkinson's disease exhibit a variety of motor deficits which can
      ultimately result in complete disability. The primary objective of this study was
      to quantitatively evaluate the effect of osteopathic manipulative treatment (OMT)
      on the gait of patients with Parkinson's disease. Ten patients with idiopathic
      Parkinson's disease and a group of eight age-matched normal control subjects were
      subjected to an analysis of gait before and after a single session of an OMT
      protocol. A separate group of 10 patients with Parkinson's disease was given a
      sham-control procedure and tested in the same manner. In the treated group of
      patients with Parkinson's disease, statistically significant increases were
      observed in stride length, cadence, and the maximum velocities of upper and lower
      extremities after treatment. There were no significant differences observed in
      the control groups. The data demonstrate that a single session of an OMT protocol
      has an immediate impact on Parkinsonian gait. Osteopathic manipulation may be an
      effective physical treatment method in the management of movement deficits in
      patients with Parkinson's disease.

PMID- 10079642
TI  - Opinions of MDs, RNs, allied health practitioners toward osteopathic medicine and
      alternative therapies: results from a Vermont survey.
AB  - The authors surveyed 191 allopathic physicians (MDs), registered nurses (RNs),
      and allied health professionals (AHPs) regarding their opinions toward
      osteopathic medicine and alternative therapies. A self-administered questionnaire
      was distributed to these healthcare professionals practicing in a rural region of
      west-central Vermont. Participants responded to six questions concerning
      osteopathic medicine and 18 types of alternative therapies. These questions
      addressed safety issues, efficacy, personal experience, patient referrals,
      interest in learning more about alternative medicine, and whether alternative
      medicine should be provided at the regional hospital. The number of positive
      responses was totaled as a positive opinion score (POS) for each respondent.
      Survey results indicated that MDs' general acceptance of osteopathic medicine was
      less than that of relaxation techniques, massage therapy, self-help groups, and
      acupuncture. Allopathic physicians' opinions toward osteopaths mirrored that
      shown toward chiropractors. Nevertheless, MDs responded more positively to
      osteopathy than did RNs and AHPs. Overall, RNs had a higher opinion of
      alternative therapies (mean POS 50.4) than did AHPs (mean POS 41.7) or MDs (mean
      POS 36.0; F = 4.98; P-value = 0.009). Among MDs, primary care providers averaged
      a POS of 41.1, while specialists had a mean POS of 24.0 (F = 6.85; P-value =
      0.012). Overall, female respondents had a mean POS of 45.7 and men had a mean POS
      of 37.0 (F = 3.91; P-value = 0.051). The POS did not correlate with age
      (Pearson's r test; r = -0.105).

PMID- 10079643
TI  - Hairy cell leukemia with an associated lupus-type anticoagulant.
AB  - Hairy cell leukemia is a rare, lymphoproliferative disorder usually of B-cell
      origin. It affects men more often than women by a ratio of 4:1, with
      approximately 600 cases per year in the United States. Leukemias in general are
      known to be associated with coagulopathies; however, the case reported here
      represents only the fourth reported case of hairy cell leukemia with an
      associated lupus anticoagulant. The lupus anticoagulant is unusual in that it is
      not truly a coagulation-preventing entity, but rather may result in a
      hypercoagulable state. The nomenclature for this manifestation derives from its
      ability to interfere with in vitro phospholipid-dependent tests of coagulation.
      This report includes a review and discussion of the case presented, as well as a
      review of both hairy cell leukemia and the lupus anticoagulant.

PMID- 10079644
TI  - Perforation of acquired small bowel diverticulum.
AB  - A 77-year old woman was seen with an unusual pathologic entity after emergent
      abdominal exploration--a ruptured small bowel diverticulum. This patient had a
      known previous history of colonic diverticulosis when she had acute onset of
      severe abdominal pain. The patient underwent an exploratory laparotomy with
      resection of representative segments of small and large bowel. The large bowel
      had evidence of diverticulosis, while the small bowel resected segment had
      evidence of diverticulitis with rupture. An extensive review of the literature
      revealed a very small number of reported cases in the world literature (less than
      150 cases). We reviewed the history of reported cases of ruptured and nonruptured
      small bowel diverticular disease, as well as this case.

PMID- 10079645
TI  - Tetracycline: effect on fetal bone growth.

PMID- 10079646
TI  - Corticosteroid therapy article helpful to hospital pharmacists.

PMID- 10079647
TI  - Availability of primary care providers and pharmacists in the United States.
AB  - OBJECTIVE: To determine the rural distribution of primary care providers (primary
      care physicians, physician assistants, nurse practitioners, and nurse midwives)
      and pharmacists. DESIGN: Five-digit ZIP code mapping to study the availability of
      primary care providers and pharmacists, alone and in combinations, in rural areas
      and ZIP code-based health professional shortage areas (HPSAs). National averages
      for annual physician visits for hypertension, asthma, and diabetes were used to
      estimate the sufficiency of the rural physician supply. SETTING: Rural areas of
      the United States. RESULTS: In rural areas, all providers were present in lower
      densities than national averages, particularly in HPSAs. The primary care
      physician supply was insufficient to meet national averages for office visits for
      hypertension, asthma, and diabetes. Among available providers, the most prevalent
      co-presence was primary care physician with pharmacist. HPSAs showed very low
      physician density (1 per 22,122), and the most prevalent providers were
      pharmacists. States varied widely in provider density. CONCLUSION: Despite
      longstanding efforts and the expansion of managed care, primary care providers
      remain in short supply in rural areas, especially ZIP code-based HPSAs. Making
      the best use of available providers should be encouraged. The continued shortfall
      of primary care providers in rural areas, particularly HPSAs, makes it logical to
      use other available providers and combinations to increase health care access.
      Pharmacists could increase care for patients with conditions treated with
      medications. Other available providers, based on skills and work site, could also
      offset shortages.

PMID- 10079648
TI  - Pharmacists' decision to undertake a mid-career residency.
AB  - OBJECTIVE: To outline factors motivating a pharmacist who has been in practice
      for five or more years to pursue a residency, and to compare the advantages and
      disadvantages of completing a residency. DESIGN: Descriptive study. Program
      directors from all residency programs accredited by the American Society of
      Health-System Pharmacists were contacted by mail to inquire about the number of
      past or current residents of their programs who could participate in the survey.
      From their responses we identified 111 potential participants. Postage-paid
      survey packets were then sent to the program directors, to be forwarded to the
      residents. The first section of the survey gathered demographic information; the
      second section focused on respondents' reasons for pursuing a pharmacy residency,
      the obstacles they had to overcome, and the benefits gained from completion of a
      residency. RESULTS: 62 respondents (56.0%) were eligible for inclusion in the
      data analysis. Professional growth was the most important reason given for
      pursuing a mid-career residency (n = 25; 40.3%). For 20 (32.3%) respondents,
      money or a decrease in salary was the "biggest obstacle" to pursuing a residency,
      and 18 (29.0%) cited family obligations. The most important benefits gained from
      the residency experience were improved marketability (40.0%) and skills (33.3%).
      CONCLUSION: Although challenging and demanding, a mid-career residency can be a
      rewarding experience for the practicing pharmacist. A residency will be of value
      to a mid-career pharmacist seeking professional growth and job satisfaction,
      rather than an increase in salary, through a change in career direction.

PMID- 10079649
TI  - Compatibility of etoposide phosphate with selected drugs during simulated Y-site
      injection.
AB  - OBJECTIVE: To evaluate the physical compatibility of etoposide phosphate with 101
      selected secondary drugs, including antineoplastic chemotherapy agents, anti
      infectives, and supportive care drugs, during simulated Y-site injection. DESIGN:
      Five-milliliter samples of etoposide 5 mg/mL as phosphate in 5% dextrose
      injection were mixed with 5 mL of the selected drugs diluted in 5% dextrose
      injection or, if necessary to avoid incompatibilities with the diluent, 0.9%
      sodium chloride injection. Samples were examined visually in normal fluorescent
      light with the unaided eye and using a Tyndall beam (high-intensity
      monodirectional light) to enhance the visibility of small particles and low-level
      haze. Turbidity of each sample was measured. In selected samples, electronic
      particle content assessment was performed. All of the samples were assessed
      initially and at one and four hours. RESULTS: Most of the secondary drugs were
      physically compatible with etoposide phosphate during the four-hour observation
      period. However, seven drug combinations had incompatibilities that included
      color change, increase in haze or turbidity, particulate formation, and gross
      precipitation. The drugs that were observed to be physically incompatible with
      etoposide phosphate were amphotericin B, cefepime hydrochloride, chlorpromazine
      hydrochloride, imipenem-cilastatin sodium, methylprednisolone sodium succinate,
      mitomycin, and prochlorperazine edisylate. CONCLUSION: Etoposide 5 mg/mL as
      phosphate in 5% dextrose injection is physically compatible for four hours at
      room temperature during simulated Y-site administration with 94 of the 101 drugs
      selected. Simultaneous Y-site administration of etoposide phosphate with the
      seven incompatible drugs should be avoided.

PMID- 10079650
TI  - Physical and chemical stability of etoposide phosphate solutions.
AB  - OBJECTIVE: To evaluate the physical and chemical stability of etoposide phosphate
      solutions over 7 days at 32 degrees C and 31 days at 4 degrees C and 23 degrees
      C: (1) at etoposide concentrations of 0.1 and 10 mg/mL as phosphate in 0.9%
      sodium chloride injection and 5% dextrose injection and (2) at etoposide
      concentrations of 10 and 20 mg/mL as phosphate in bacteriostatic water for
      injection packaged in plastic syringes. DESIGN: Test samples of etoposide
      phosphate were prepared in polyvinyl chloride (PVC) bags of the two infusion
      solutions at etoposide concentrations of 0.1 and 10 mg/mL as phosphate.
      Additional test samples were prepared in bacteriostatic water for injection
      containing benzyl alcohol 0.9% at etoposide concentrations of 10 and 20 mg/mL as
      phosphate and were packaged in 5 mL plastic syringes. Evaluations for physical
      and chemical stability were performed initially; after 1 and 7 days of storage at
      32 degrees C; and after 1, 7, 14, and 31 days of storage at 4 degrees C and 23
      degrees C. Physical stability was assessed using visual observation in normal
      light and using a high-intensity monodirectional light beam. Turbidity and
      particle content were measured electronically. Chemical stability of the drug was
      evaluated by using a stability-indicating high-performance liquid chromatographic
      (HPLC) analytic technique. RESULTS: All samples were physically stable throughout
      the study. Little or no change in particulate burden and haze level were found.
      In the intravenous infusion solutions, little or no loss of etoposide phosphate
      occurred in any of the samples throughout the study period. The 10 and 20 mg/mL
      samples in bacteriostatic water for injection repackaged in syringes were also
      stable throughout the study, exhibiting a maximum of 6% or 7% loss after 31 days
      of storage at 23 degrees C and less than 4% in 31 days at 4 degrees C.
      CONCLUSION: Etoposide phosphate prepared as intravenous admixtures of etoposide
      0.1 and 10 mg/mL as phosphate in 5% dextrose injection and 0.9% sodium chloride
      injection in PVC bags and as etoposide 10 and 20 mg/mL as phosphate in
      bacteriostatic water for injection packaged in plastic syringes is physically and
      chemically stable for at least 7 days at 32 degrees C and 31 days at 4 degrees C
      and 23 degrees C. This new water-soluble phosphate-ester of etoposide formulation
      solves the precipitation problems associated with the old organic solvent and
      surfactant-based formulation.

PMID- 10079651
TI  - New drugs of 1998.
AB  - OBJECTIVE: To provide information regarding the most important properties of the
      new therapeutic agents marketed in 1998. DATA SOURCES: Published studies, drug
      information reference sources, and product labeling. DATA SYNTHESIS: In 1998, 44
      new therapeutic agents were marketed. The indications and information on dosage
      and administration for each new agent are reviewed, as are the most important
      pharmacokinetic properties, adverse events, drug interactions, and other
      precautions. Practical considerations for the use of the new agents are also
      discussed. Where possible, the properties of the new drugs are compared with
      those of older drugs marketed for the same indications. CONCLUSION: A number of
      the new therapeutic agents marketed in 1998 have important advantages over older
      medications. An understanding of the properties of these agents is important for
      the pharmacist to effectively counsel patients about their use and to serve as a
      valuable source of information for other health professionals regarding these
      drugs.

PMID- 10079652
TI  - New OTC drugs and devices 1998: a selective review.
AB  - OBJECTIVE: To create a heightened awareness of the marketing strategy of dual
      labeling, i.e., labeling of two benefits on a nonprescription drug product, and
      to review a selection of new self-care products that became available in 1998 for
      consumer use in the United States. DATA SOURCES: Recent clinical and
      pharmaceutical industry literature. DATA SYNTHESIS: It is critical for the
      pharmacist to be aware of the use of dual labeling and to be able to
      appropriately counsel and direct patients on how to read and understand dual
      labeling. In addition, numerous nonprescription products, including home
      diagnostic products and accessories, will continue to become available on the
      U.S. market. It is important that the pharmacist become as knowledgeable as
      possible about these, and be well positioned to educate patients about their
      appropriate use. CONCLUSION: The new products cited in this review represent
      valuable new additions to the self-care product pool.

PMID- 10079653
TI  - Treatment of postherpetic neuralgia.
AB  - OBJECTIVE: To review treatment options for postherpetic neuralgia (PHN). DATA
      SOURCES: Clinical literature selected by the authors accessed via MEDLINE. Search
      terms included postherpetic neuralgia, capsaicin, antidepressants,
      anticonvulsants, and lidocaine. STUDY SELECTION: Controlled trials relevant to
      PHN. DATA SYNTHESIS: Traditional analgesics offer little benefit for the
      treatment of PHN. The best results for pain relief have come from capsaicin and
      tricyclic antidepressants. Anticonvulsants have also been used, although the
      number of studies evaluating this is limited. More invasive therapies, such as
      transcutaneous electrical nerve stimulation and nerve blocks, can be considered
      if other therapies fail. CONCLUSION: Early diagnosis and treatment of herpes
      zoster may offer patients the best chance of preventing the development of PHN.
      However, if PHN does develop, the patient should seek treatment early for the
      best chance of pain relief.

PMID- 10079654
TI  - Medication challenges in the assisted living facility.
AB  - OBJECTIVE: To review current challenges to the provision of safe and effective
      pharmaceutical care in assisted living facilities. DATA SOURCES: Current
      literature. DATA SYNTHESIS: The assisted living industry has experienced
      tremendous growth and offers pharmacists lucrative business opportunities.
      However, pharmacists must understand the varied nature of both the facilities and
      the residents. Assisted living residents are entitled to independence and
      privacy, a fact that presents many challenges in terms of monitoring the safe and
      accurate administration of medications. CONCLUSION: Assisted living facilities
      provide elderly residents a new and unique blend of independent living and daily
      support. To provide effective pharmacy services to these facilities, pharmacists
      must consider their specific needs in terms of medication use processes,
      packaging, delivery, documentation, and storage.

PMID- 10079655
TI  - Evaluation of a pharmaceutical care education series for chain pharmacists using
      the focus group method.
AB  - OBJECTIVES: (1) Describe a pharmaceutical care education program presented to a
      group of pharmacists employed by a large pharmacy chain; (2) present the results
      of a formative evaluation of that program, and show how these can be used to
      improve subsequent offerings of the program as well as to enhance the efforts of
      other pharmacies and colleges involved in similar ventures; and (3) describe the
      focus group method in detail and demonstrate its usefulness as an evaluation
      tool. DESIGN AND PARTICIPANTS: Two pharmacist focus groups and two patient focus
      groups. SETTING: Chain pharmacy corporation and two colleges of pharmacy. MAIN
      OUTCOME MEASURES: Effects on attitudes and practice. RESULTS: The focus group
      method is useful for this type of evaluation. The educational series had a
      positive effect on pharmacists' attitudes and reported practice behavior.
      However, these improvements were not obvious to patients. Small group learning
      modules that include cases or problem-based exercises are probably effective
      vehicles for achieving educational goals. CONCLUSION: The chain pharmacy
      corporation should revise the educational program and expose more pharmacist
      employees to it. This company and others should consider providing off-site, in
      person education to employee pharmacists that makes use of an interactive, small
      group format. Although effective, the focus group method could have been improved
      by a more rigorous patient recruitment process and greater structure to the
      debriefing sessions for staff.

PMID- 10079656
TI  - First MAb approved for treatment of metastatic breast cancer.

PMID- 10079657
TI  - Recommend that travelers get vaccine advice.

PMID- 10079658
TI  - Herbal products and the Internet: a marriage of convenience.

PMID- 10079659
TI  - The management of cancer in the elderly.
AB  - The treatment of elderly patients with cancer requires a multidisciplinary
      approach if optimal locoregional control of disease and survival are to be
      achieved. Wherever possible, the surgical, radiotherapeutic and chemotherapeutic
      regimens given to elderly patients with cancer should be comparable with those
      currently used for the treatment of younger patients with cancer. However, the
      morbidity (physical and psychological) of therapy must be evaluated against the
      likely benefits to ensure that elderly patients with cancer receive both optimal
      management and quality of life.

PMID- 10079660
TI  - The drawbacks of overspecialisation.
AB  - In the March 1997 issue of Surgery, Professor Irving Taylor of University College
      London Medical School observed that overspecialisation in surgery may have gone
      too far. I have, in the February 1998 issue of Surgery, pointed to the damage
      that specialisation has done to surgery in the third world. The President of the
      College and the Editor of the Journal have decided, rather than reprinting my
      essay, to ask me to enlarge on the topic. In this article, by necessity, I will
      be covering issues that I first raised in the Surgery article. To be invited to
      partake in a debate of such importance is a great honour. That this honour was
      bestowed upon a Fellow of the Association of Surgeons of East Africa, which
      organised the first symposium on "Surgery in the District Hospital", is of great
      significance to east African surgery.

PMID- 10079661
TI  - Screening relatives of patients with colorectal cancer: the need for continuing
      education.
AB  - Individuals at risk of familial colorectal cancer may be identified from their
      pedigree but screening guidelines are limited. We wished to assess the opinion of
      consultants in the region of the value of screening for familial colorectal
      cancer. All consultant general surgeons and consultant gastroenterologists in
      South (West) Thames received a questionnaire. This considered the current
      screening practice of the consultant for colorectal cancer, their opinion of
      screening patients with a positive family history, and their screening regimen
      for particular family history scenarios. Seventy-one (62.8%) of consultants
      replied. Forty-two consultants regularly performed screening colonoscopy (72%)
      with a median of 15 patients each year (range 2-130). Of these, 23 said that the
      number screened was limited by resources. Three percent thought regular screening
      of individual at increased risk of developing colorectal cancer should be yearly,
      42% 3 yearly, and 42% 5 yearly. Regarding the risk of dying from colorectal
      cancer, 14% would screen for a risk of greater than 1 in 6, 45% 1 in 10, 18% 1 in
      20, and 10% 1 in 50. Only half of the consultants agreed with published
      guidelines regarding the age of an index case of colorectal cancer below which
      they would screen 1st degree relatives. There was substantial variation in
      suggested screening regimens for the sample family pedigrees. There is wide
      variation in indications for and clinical practice of screening for familial
      colorectal cancer and evidence-based refinement of guidelines and increased
      specialist referral could rationalise resources.

PMID- 10079662
TI  - Supervised surgical trainees can perform pancreatic resections safely.
AB  - With the recent changes in surgical training and sub-specialisation, the role of
      surgical trainees in more advanced surgical procedures has come into question. In
      order to examine this further, we analysed the early outcome of patients in a
      single surgical unit undergoing pancreatic resections, with regard to the grade
      of the surgeon performing the operation. Between January 1994 and May 1996, data
      were collected prospectively on all the patients undergoing pancreatic resections
      with regards to the grade of the surgeon performing the procedure and the early
      outcome following the operation. Sixty-two patients underwent pancreatic
      resections for both benign and malignant diseases. Overall, 19 operations (31%)
      were performed by trainees under supervision, 14 of the 40 pancreatico
      duodenectomies (35%) and 5 of the 19 left partial pancreatectomies (26%). All 3
      total pancreatectomies were carried out by consultants. In the 43 patients
      operated upon by the consultants, there were 8 anastomotic leaks (19%) and 1
      death. In the 19 patients operated upon by the supervised trainees, there were
      only 2 anastomotic leaks (11%) and no deaths. This series has demonstrated that
      in a unit with a major interest and large workload in pancreatic surgery, there
      appears to be no difference between a consultant and a supervised trainee in the
      early outcome following pancreatic resections.

PMID- 10079663
TI  - Prospective study of high dependency care requirements and provision.
AB  - BACKGROUND AND PURPOSE OF THE STUDY: To compare the level of post-operative care
      requested for surgical patients with that provided in a Scottish teaching
      hospital. METHODS: A three months pragmatic prospective observational study was
      undertaken which included patients undergoing major surgery excluding
      gynaecological and elective orthopaedic surgery. A study specific questionnaire
      was used to collate the information. The data were inputted to DataEase 4.5 and
      subsequently exported to SPSSWIN version 6.1.3 for analysis. The main outcome
      measure was the level of care requested and the level of care actually received.
      MAIN FINDINGS: Among 1363 patients a total of 1395 operations were performed. The
      median age was 59 years with a male: female ratio of 1.1:1. The type of admission
      was elective in 58% and emergency in 42% of cases. The operations were elective
      in 44% and nonelective in 56% of cases. The ASA score was 3 or greater in 33% of
      patients. The optimum level of care requested by surgeons and anaesthetists was
      intensive therapy unit (ITU) in 9.7% and high dependency unit (HDU) in 23.6% of
      patients. Twenty-one (15.9%) of 132 ITU requests and 256 (73.8%) of 349 HDU
      requests were not met immediately post-operatively. Overall mortality was 1.5%.
      For those patients who received optimum requested care mortality was 1.2% and, in
      those patients who did not receive optimum requested care, mortality was 3.1% (p
      < 0.038: Chi-square). CONCLUSION: This study confirms a significant lack of
      access to properly staffed and equipped HDU facilities in a major teaching
      hospital with a consequent increase in mortality in those not receiving optimal
      post-operative care.

PMID- 10079664
TI  - The soft tissue management of children's open tibial fractures.
AB  - A series of 49 children admitted with a diagnosis of open tibial fracture was
      reviewed with particular regard to soft tissue management. Injuries were grouped
      according to the Gustilo classification. Twenty-two patients had Grade I
      fractures, 11 Grade II and 16 Grade III (4 Grade IIIa, 11 Grade IIIb and one
      Grade IIIc). Patients were managed by early lavage and debridement under general
      anaesthesia, followed by immobilisation. Local transposition flaps were utilised
      in 10 patients and provided reliable soft tissue cover. A free tissue transfer
      was performed in only one patient. Complications appeared to be associated with
      delayed involvement by plastic surgeons.

PMID- 10079665
TI  - Observer agreement analysis of MRI grading of knee osteoarthritis.
AB  - The aim of the study was to use Kappa statistical analysis to assess the inter
      and intraobserver agreement of the interpretation of the osteoarthritis changes
      observed on a FISP sequence, 1.0 Tesla, MRI analysis of the articular cartilage
      in 30 knees. The images were read on two separate occasions by three observers.
      The best agreement was seen in the patello-femoral compartment. The most
      experienced of the assessors produced the more consistent results. The results of
      the interobserver agreement had mainly "slight" or "fair" agreement. Our results
      are disappointing and accordingly, we have reservations about the use of MRI in
      the assessment of osteoarthritis of the knee.

PMID- 10079666
TI  - Surgery and the information age.
AB  - Surgeons' basic competency relies upon their ability to combine their existing
      knowledge and practical skills in the care of their patients, and also upon
      keeping up to date and encompassing change. We now live in a society which has
      become accustomed to receive a constant flow of up-to-date information about the
      world around it. With recent developments, including the Internet, the World Wide
      Web, and advances in personal computer systems, the pace of change of information
      technology (IT) has been increasing. These changes have had a significant impact
      upon surgery, and it is now becoming necessary to be able to make use of these
      new resources to function effectively in modern practice. This article will
      outline some of the more important topics relating to IT in surgical practice as
      an introduction to a series on this subject which will be appearing in
      forthcoming issues of the Journal.

PMID- 10079667
TI  - Assessment of an electronic mailing list for orthopaedic and trauma surgery.
AB  - Medical electronic mailing lists have grown rapidly with the evolution of the
      Internet. The purpose of this paper was to assess the content and academic
      quality and of an electronic mail discussion list "Orthopod" dedicated to
      research in orthopaedic and trauma surgery. A retrospective analysis was
      undertaken of four months of web-based archive of communication through the
      Orthopod mailing list http:(/)/www.mailbase.ac.uk/lists/Orthopod. At the end of
      this study period there were 505 members of the Orthopod list. The main outcome
      measures of this paper were number of messages, type of messages, number of
      contributors, designation of contributor and number of topics referenced. On
      average 276 messages were posted each month. The mean number of messages per
      contributor per month only varied between 2.3 and 2.5. On average 54% of message
      threads contained at least one reference. At least 77% of the patient history and
      general threads had input from senior orthopaedic staff. The quantity of
      information on the Internet need not be a substitute for quality in orthopaedic
      and trauma surgery mailing lists. The Orthopod Electronic mail discussion list is
      another medium for the circulation of good quality surgical information. Orthopod
      provides a unique international electronic forum list for trauma and orthopaedic
      surgeons worldwide.

PMID- 10079668
TI  - Anterior resection with total mesorectal excision.

PMID- 10079669
TI  - Limb shortening for the management of leg length discrepancy.
AB  - Limb shortening is an option to manage leg length discrepancy (LLD). Before
      skeletal maturity, a LLD between 2 and 5 cm can be corrected by epiphyseodesis
      (open or closed) or stapling. All these procedures require exact timing of
      surgery. In skeletally mature patients, shortening of the femur is considered
      safer than tibial shortening. Subtrochanteric and supracondylar osteotomies fixed
      with a blade-plate can be used to correct associated deformity. Mid-shaft
      shortening can be performed by a closed or open method. Closed shortening has
      been widely used, but frequent malrotation, loss of function and acute
      respiratory distress syndrome following reaming have been reported. Therefore,
      the use of a nail locked proximally and distally, and caution in reaming the
      canal, are strongly recommended. For LLDs greater than 10 cm, lengthening should
      be considered, although a one-stage two-limb procedure can be used, whereby
      shortening is performed on the longer limb, and the excised bone segment is
      implanted in the contralateral limb to be lengthened. However, when shortening
      procedures are performed in skeletally immature patients, they require precise
      timing, and indications and technical details must be strictly observed.

PMID- 10079670
TI  - Optimal education techniques for basic surgical trainees: lessons from education
      theory.
AB  - "Calmanisation" of surgical training and the introduction of the "New Deal" on
      doctor's hours has led to a reduction in "in service" training and a
      proliferation of training courses. Little research has been done into the optimum
      design of these courses. Education theory has shown that individuals have optimal
      learning styles and that these styles tend to be generalised across professional
      groups. It was decided, therefore, to investigate the optimal learning styles of
      basic surgical trainees. A learning style inventory was used to assess the
      preferred learning style of 52 basic surgical trainees. The predominant learning
      styles (86.5%) were convergent (n = 31) or accommodative (n = 14) whilst only 5
      (9.6%) assimilative and 2 (3.9%) divergent styles were detected. Convergent and
      accommodative learners rely principally on hands on experience and problem
      solving as their optimal learning technique. Given the shorter hours and duration
      of Basic Surgical Training, in service practical training and surgical courses
      should be structured accordingly.

PMID- 10079671
TI  - Cystic hygroma in an adult: a case report.
AB  - Cystic hygromas are benign lesions arising due to an abnormality in lymphatic
      development and only rarely present in adults. Adequate radiological imaging
      prior to surgery is important as incomplete excision often leads to recurrence.
      Several adjunctive therapies have been shown to be beneficial in recurrent or
      inaccessible lesions but these are not in common use. We describe the case of a
      cystic lymphangioma appearing in adulthood that presented a diagnostic and
      therapeutic challenge.

PMID- 10079672
TI  - Acute small bowel obstruction due to ileal endometriosis: a case report and
      literature review.
AB  - A young women presented with non-resolving acute small bowel obstruction and was
      found to have a stricture in the distal ileum at laparotomy. Histologically this
      was due to endometriosis. Resection of the involved segment gave excellent
      results.

PMID- 10079673
TI  - Synchronous and metachronous gastric adenocarcinoma: case report and literature
      review.
AB  - Whilst synchronous adenocarcinoma of the stomach is well documented, metachronous
      primary disease is exceedingly rare. We report a man with a family history of
      colonic and gastric cancer, who underwent a resection of a Duke's C
      adenocarcinoma of the rectum, aged 56 years, and a proximal partial gastrectomy
      for synchronous stage 1 gastric adenocarcinomas of the lesser curve, aged 61
      years. Nine years later, a metachronous gastric primary was discovered in the
      gastric remnant, necessitating total gastrectomy. Total gastrectomy is the
      operation of choice for synchronous gastric primaries as it ensures clearance and
      prevents metachronous growth. However, it may not be appropriate for all gastric
      cancer as operative morbidity and mortality are increased, and because
      synchronicity and metachronicity of gastric cancer are uncommon. Moreover, there
      are no consistent data to demonstrate a survival advantage for total compared
      with partial gastrectomy for operable gastric cancer. If, after partial
      gastrectomy, synchronous disease is detected in the resected specimen (as in this
      reported case), endoscopic surveillance for metachronous disease is advised,
      since this may be amenable to surgical cure.

PMID- 10079674
TI  - Delayed dislocation of radial head following upper radial epiphysial injury.
AB  - Injury to the upper radial epiphysis is mainly a radiological diagnosis. Delayed
      dislocation of the radial head following such injuries, where there is no
      evidence of primary subluxation or dislocation, has not been recorded in the
      literature. We have identified three such cases that needed open reduction. As
      long term results of delayed treatment of dislocation of any joint is not good,
      we advocate the awareness of this complication and also a longer period of
      routine follow-up (up to a year) of all upper radial epiphysial injuries, to
      avoid a catastrophe in an entirely preventable situation.

PMID- 10079675
TI  - Oesophagectomy volume and centralization of cancer surgery.

PMID- 10079676
TI  - Further uses of polymethylmethacrylate in orthopaedic surgery.

PMID- 10079677
TI  - Births, marriages, divorces and deaths. Provisional data for October 1998.

PMID- 10079678
TI  - Cerebral complications of diabetes: clinical findings and pathogenetic
      mechanisms.
AB  - This review describes the cerebral complications of diabetes mellitus from a
      neuropsychological, neurophysiological and neuroradiological perspective. In
      addition, possible pathogenetic mechanisms are discussed. Neuropsychological
      studies of diabetic patients generally report modest deficits in learning and
      memory and information processing. Notably, in elderly diabetic patients
      cognitive deficits may be more prominent. Recent epidemiological studies show
      that in the elderly diabetes is associated with an increased risk for dementia.
      Neurophysiological studies show increased latencies of evoked potentials and
      event-related potentials. Neuroradiological findings are enhanced peripheral and
      central cerebral atrophy, as well as focal lesions. The pathophysiology of the
      effects of diabetes on the brain has not been fully elucidated. The putative
      involvement of cerebral metabolic and microvascular disturbances, similar to
      those implicated in the pathogenesis of peripheral diabetic neuropathy, is
      discussed. In addition, the role of repeated hypoglycaemic episodes,
      cerebrovascular disease and hypertension is addressed. Finally, the potential
      differential effects of insulin dependent and non-insulin dependent diabetes on
      the brain are discussed, as well as possible links with brain ageing.

PMID- 10079679
TI  - Diagnosis, pathogenesis and treatment of the myeloproliferative disorders
      essential thrombocythemia, polycythemia vera and essential megakaryocytic
      granulocytic metaplasia and myelofibrosis.
AB  - According to strict clinical, hematological and morphological criteria, the
      Philadelphia (Ph) chromosome negative chronic myeloproliferative disorders
      essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid
      (megakaryocytic/granulocytic) metaplasia (AMM) or idiopathic myelofibrosis (IMF)
      are three distinct disease entities with regard to clinical manifestations,
      natural history and outcome in terms of life expectancy. As clonality studies
      have clearly demonstrated that fibroblast proliferation in AMM, as well as in
      many other conditions such as advanced stages of Ph(+)-essential thrombocythemia,
      Ph(+)-granulocytic leukemia, and Ph(-)-polycythemia vera, is polyclonal
      indicating that myelofibrosis is secondary to the megakaryocytic granulocytic
      metaplasia in these various conditions, AMM is illogically labeled as IMF. As
      abnormal megakaryocytic granulocytic metaplasia is the essential feature
      preceding the early prefibrotic stage of AMM, the term essential megakaryocytic
      granulocytic metaplasia (EMGM) can readily be used to characterize this condition
      more appropriately at the biological level. Clinical, hematological and
      morphological characteristics, in particular megakaryocytopoiesis and bone marrow
      cellularity, reveal diagnostic features, which enable a clear-cut distinction
      between ET, PV and EMGM or classical IMF. The characteristic increase and
      clustering of enlarged megakaryocytes with mature cytoplasm and multilobulated
      nuclei and their tendency to cluster in a normal or only slightly increased
      cellular bone marrow represent the hallmark of ET. The characteristic increase
      and clustering of enlarged mature and pleiomorphic megakaryocytes with
      multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked
      hypercellular bone marrow with hyperplasia of dilated sinuses are the specific
      diagnostic features of untreated PV. EMGM, including the early prefibrotic stages
      as well as the various myelofibrotic stages of classical IMF appear to be a
      distinct neoplastic dual proliferation of abnormal megakaryopoiesis and
      granulopoiesis. The histopathology of the bone marrow in prefibrotic EMGM and in
      classical IMF is dominated by atypical, enlarged and immature megakaryocytes with
      cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and
      during follow-up. Myelofibrosis in ET, PV and EMGM is graded into: no reticulin
      fibrosis (MF0), early reticulin fibrosis (MF1), advanced reticulin sclerosis with
      minor or moderate collagen fibrosis (MF2) and advanced collagen fibrosis with
      osteosclerosis (MF3). Myelofibrosis is not a feature of ET at diagnosis and
      during long-term follow-up. Myelofibrosis may be present in a minority of PV
      patients at diagnosis and usually becomes apparent during long-term follow-up in
      the majority of PV-patients. Myelofibrosis secondary to the abnormal
      megakaryocytic and granulocytic myeloproliferation constitutes a prominent
      feature in the majority of EMGM/IMF at time of diagnosis and usually progresses
      more or less rapidly during the natural history of the disease. Life expectancy
      is normal in ET, normal during the 1st ten years and compromised during the 2nd
      ten years follow-up in PV, but significantly shortened in the prefibrotic stage
      of EMGM as well as in the various myelosclerotic stages of classical IMF. First
      line treatment options in prospective randomized clinical trials of newly
      diagnosed MPD-patients are control of platelet function with low-dose aspirin
      versus reduction of platelet count with anagrelide, interferon or hydroxyurea in
      ET; control of platelet and erythrocyte counts by interferon alone versus
      bloodletting plus hydroxyurea on indication in PV; interferon versus no treatment
      in the early stages of EMGM; a wait and see strategy in the fibrotic stages of
      EMGM or classical IMF with favorable prognostic factors, and bone marrow
      transplantation in classical IMF with poor prognostic factors at presentation or
      during short-term follow-up.

PMID- 10079680
TI  - Prognostic factors for successful insulin therapy in subjects with type 2
      diabetes.
AB  - OBJECTIVE: To assess which factors influence or predict the efficacy of insulin
      therapy in subjects with type 2 diabetes, who were poorly controlled despite
      maximal doses of oral glucose lowering agents. RESEARCH DESIGN AND METHODS:
      Seventy-five patients with type 2 diabetes participated (mean age (+/- SD), 67 +/
      8 years; body mass index, 25.8 +/- 5.0 kg/m2; median time since diagnosis of
      diabetes, 8 years (range 1-36); 27 males and 48 females). They were transferred
      to insulin therapy, in which case either insulin alone, or a combination of
      insulin and glibenclamide was employed. The importance of baseline parameters
      (glycaemic control, beta-cell function, measures of insulin resistance) was
      assessed by comparing good and poor responders (defined as achieved HbA1c < 8.0
      or > 9.0%) to insulin therapy, and by multiple logistic regression analysis of
      these baseline parameters and achieved metabolic control. RESULTS: During insulin
      therapy, HbA1c levels decreased from 10.9 +/- 1.3 to 8.2 +/- 1.1% (p < 0.001),
      and fasting blood glucose levels decreased from 14.0 +/- 2.3 to 8.2 +/- 2.1
      mmol/l (p < 0.001). Thirty patients reached HbA1c levels < 8.0%, 21 of them even
      < 7.5%. The mean increase in body weight was 4.5 kg. HbA1c after 6 months was 7.0
      +/- 0.6% in the good responders, and 9.8 +/- 0.6% in the poor responders (p <
      0.001), despite a comparable insulin dose. Baseline metabolic control was similar
      in both groups. Also, glucagon-stimulated and calculated insulin secretion, as
      well as parameters of insulin resistance, such as fasting serum insulin levels,
      free fatty acids, and serum triglycerides, were not different between both
      groups, and certainly not higher in the poor responders. Also previous metformin
      use was not different. However, poor responders were more obese than good
      responders, and had significantly longer known duration of diabetes. Multiple
      logistic regression confirmed that only duration of diabetes and body mass index
      were independent predictors of response to insulin therapy. CONCLUSIONS: We
      conclude that in elderly patients with type 2 diabetes improvement of glycaemic
      control can be achieved at the expense of some weight gain. Measurement of
      residual insulin secretion prior to institution of insulin treatment does not
      discriminate between good and poor responders to this model of therapy.
      Especially in obese patients with longer duration of diabetes more attention is
      needed in order to achieve optimal glycaemic control. Combination of insulin with
      newer drugs, like thiazolidinediones, may perhaps achieve this.

PMID- 10079681
TI  - Swelling of hand and forearm caused by Mycobacterium bovis.
AB  - A 75-year-old native Dutch farmer presented with a painless swelling of his right
      hand extending into his forearm, accompanied by general malaise and low grade
      fever. His medical history revealed coxitis tuberculosa in 1954 and injury of the
      same hand in 1978. His present swelling appeared to be caused by Mycobacterium
      bovis, probably due to endogenous reactivation. Whether the mycobacteria reached
      the hand hematogenously or were directly inoculated at the time of injury of his
      hand in 1978 remains unclear.

PMID- 10079682
TI  - Ticlopidine-induced thrombocytopenia.
AB  - A case is presented of a 58-year-old woman developing profound thrombocytopenia
      within one week after starting treatment with ticlopidine. Ticlopidine was
      prescribed following coronary artery stenting. The patient recovered rapidly
      after discontinuation of the drug, suggesting a possible relationship between
      ticlopidine and thrombocytopenia. Haematological disorders associated with
      ticlopidine, such as neutropenia, thrombocytopenia and bone marrow aplasia, are
      rare and usually seen within the first three months of therapy. As the use of
      ticlopidine increases, clinicians should be aware of haematological complications
      associated with its use and inform their patients appropriately.

PMID- 10079683
TI  - Melioidosis.
AB  - Melioidosis is an infection with the gram-negative bacillus Burkholdria
      pseudomallei, previous known as Pseudomonas pseudomallei. We present a case
      report of a man with Non-Hodgkin's Lymphoma, who after visiting Indonesia
      presented himself with a urosepsis, with positive cultures to B. pseudomallei.
      Melioidosis is endemic in areas of southeast Asia and the northern part of
      Australia. Infection with the B. pseudomallei has a high mortality rate.
      Diagnosis can be made on the basis of cultures, the bacteria grow on standard
      media. Treatment should be based up on sensitivity studies. The optimum duration
      of therapy and choice of antibiotics remain to be determined. Due to the increase
      in travel, the infection will be seen more frequently in other parts of the
      world.

PMID- 10079684
TI  - [In memoriam. Dr. Francois Lhermitter (1921-1998)].

PMID- 10079685
TI  - Treatment of acute ischemic stroke: where are we?

PMID- 10079686
TI  - [Huntington chorea: clniical and molecular analysis in Asturian patients].
AB  - AIM AND PATIENTS: To analyse 38 patients with Huntington's disease from 27
      families. RESULTS: The CAG repeat at the huntingtin gene was expanded between 40
      and 72 times. The size in normal chromosomes varied from 12 to 30 repeats. We
      found a significantly negative correlation between the number of CAG-repeats and
      the age of clinical manifestations. However, age and clinical characteristics of
      the first symptoms were highly variable between patients with a similar size of
      the expanded allele. Patients who inherited the disease from their fathers showed
      a higher number of repeats than those who received the disease from their
      mothers. However, in one case of father to son transmission we observed a
      reduction of the number of CAG repeats. CONCLUSIONS: These data make it difficult
      to use the molecular analysis for the presymptomatic diagnosis of clinical course
      in individuals carrying the expansion.

PMID- 10079687
TI  - [Incidence of idiopathic and secondary Parkinson disease in Navarre. Population
      based case registry].
AB  - AIM: To determine the incidence of Parkinson's disease in Navarra, province of
      Spain. PATIENTS AND METHODS: All patients diagnosed as suffering from Parkinson's
      disease or related disorders for the neurologists of the region during the period
      1994-1995 inclusive were referred to the study. EUROPARKINSON protocol and an
      epidemiological questionnaire were employed for the assessment. RESULTS: A total
      of 132 cases of idiopathic (86) and secondary (45) Parkinson's disease were
      diagnosed during that period. Among men the age adjusted incidence of idiopathic
      Parkinson's disease was 10.06 x 10(5), while for women it was 4.92 x 10(5). Total
      adjusted incidence was 7.36 x 10(5). The average age at onset was 67.5 years in
      men and 72.6 years in women (p < or = 0.007). Men showed an age adjusted
      incidence of secondary parkinsonism of 3.34 x 10(5) and women of 4.23 x 10(5).
      Age at onset was earlier in women than in men (71.2 and 74.8 years,
      respectively). CONCLUSIONS: The incidence of idiopathic Parkinson's disease in
      Navarra is higher in men than in women, also supported for an earlier age at
      onset in men. The epidemiological pattern of secondary Parkinson's disease
      differs from that of the idiopathic disease.

PMID- 10079688
TI  - [Contribution of John Hughlings Jackson to the understanding of epilepsy].
AB  - The figure of J.H. Jackson is one of the most relevant in the history of
      neurology. His longest period not only during his training but also during his
      professional plenitude took place in the National Hospital. Jackson was a great
      clinician, wrote many articles and gave a lot of lectures, but never wrote either
      a treatise or a monograph about his special field. He did not carry out animal
      experiments. He introduced in Britain the use of the ophthalmoscope in the
      neurological exploration and founded the journal Brain. He was specially
      interested in language disorders, paralysis, vertigo, mental disorders, cerebral
      tumours and above all epilepsy. He systematized what we today know as complex
      partial crisis, establishing the link between the function of the temporal lobe
      and the sensorial auras, automatism's, deja-vu and jamais vu phenomena. He
      described the uncinate crisis, the topographic progression of the motor partial
      crisis and its posterior generalisation, establishing the motor pattern of
      cerebral cortex. The clinical observations of epileptic phenomena, with the
      influence of the evolutive ideas from Spencer, were the seeds for the elaboration
      of the evolutive development of the function of the nervous system. His theory
      about evolution and dissolution of the neurological functions was the starting
      point for Freud's clinical investigation. The Jacksonian set of ideas were
      experimentally proved by the neurophysiological work of Sherrington.

PMID- 10079689
TI  - [Ictal semiology of temporal partial complex seizures: usefulness for localizing
      and lateralizing the origin of the attacks].
AB  - AIM: To review signs and symptoms associated with temporal complex partial
      seizures (CPS) and their utility in the localization and lateralization of
      seizure onset. DISCUSSION: CPS are particularly resistant to the standard
      antiepileptic drugs. Since surgical treatment is a therapeutical alternative in
      patients with intractable seizures, localization and lateralization of seizure
      origin are the principal aims in the preoperative assessment. Video-EEG
      monitorization has made possible characterization of ictal behaviour and
      correlation with cerebral regions generating the epileptic discharge. Therefore,
      ictal semiology has increased its importance in the localization and
      lateralization of seizures. The utility of auras, automatisms, motor
      manifestations, speech disturbances and autonomic features have been reviewed in
      relation to this approach. CONCLUSIONS: Viscerosensorial and experiential auras
      have been associated with temporal lobe epilepsy. The automatisms are not
      exclusive of temporal seizures and may be observed in frontal epilepsy and
      parietal and occipital seizures with spreading to temporal structures. There is
      not agreement in relation to head turning and version, therefore, this clinical
      sign should be used in correlation to other clinical manifestations. Distonic
      posturing, comprehensible ictal speech and postictal dysphasia appear to be the
      most reliable clinical signs in the lateralisation of temporal lobe seizures.

PMID- 10079690
TI  - [EEG pattern indicative of dialysis encephalopathy].

PMID- 10079691
TI  - [Lower cranial nerve involvement as the initial manifestation of Lyme
      borreliosis].
AB  - Lyme disease or Lyme borreliosis is an infectious disease transmitted by ticks
      and caused by Borrelia burgdorferi. Being clinically different from Relapsing
      Fever it may cause an array of symptoms, specially cutaneous and neurological but
      also musculoskeletal and cardiac ones. Within the neurologic manifestations of
      Lyme disease the affectation of low cranial nerves is, to our knowledge,
      extremely infrequent. We present the clinical case of a 35 years old male whose
      initial symptoms were low cranial nerve dysfunction with a cerebrospinal fluid
      compatible with meningitis. Serology against Borrelia burgdorferi both in serum
      and cerebrospinal fluid was positive.

PMID- 10079692
TI  - [Neurological complications of Mediterranean boutonneuse fever. Presentation of a
      case of acute encephalomeningomyelitis and review of the literature].
AB  - Mediterranean spotted fever is an infectious disease due to Rickettsia conorii
      usually considered as benign; however, 10% of cases may have severe
      complications. We report a patient with celiac disease who developed
      encephalomeningomyelitis secondary to Mediterranean spotted fever.
      Meningoencephalitic involvement occurred during the acute phase, with myelitis
      appearing early during convalescence, as acute onset paraplegia involving the
      lumbosacral spinal cord. A magnetic resonance study showed multifocal white
      matter disturbances, with no lesions in the spinal cord. One month following
      onset, R. conorii antibodies serum level was 1/640. A cutaneous biopsy performed
      during the acute phase revealed endothelial hyperplasia, intraluminal thrombosis
      and lymphocytic perivascular infiltrate. Several immunological disturbances were
      found (circulating immune complexes, antinuclear antibodies, IgG
      paraproteinemia). The development of a systemic vasculitis is the major
      pathogenetic factor in the origin of systemic complications of Mediterranean
      spotted fever. We review the neurological syndromes reported in association with
      R. conorii infection. Our case is the second described as acute myelopathy
      complicating Mediterranean spotted fever.

PMID- 10079693
TI  - [Susac syndrome: presentation of a new case].

PMID- 10079694
TI  - [Acute familial dystonia caused by antidopaminergic drugs].

PMID- 10079695
TI  - [Cerebral infarction caused after cocaine consumption].

PMID- 10079696
TI  - [Villaret syndrome. Manifestation of carotid dissection].

PMID- 10079697
TI  - It takes determination to be a dentist.

PMID- 10079698
TI  - DSSNY adopts new ethics enforcement structure.

PMID- 10079699
TI  - Distraction osteogenesis.
AB  - Distraction osteogenesis is a surgical technique originally used to lengthen the
      long bones without bone grafting. An osteotomy is created and by slowly
      separating the two segments with specially fabricated hardware, the biological
      distractant will grow with the bone and calcify into mature bone once the
      appropriate length has been achieved. Distraction techniques have been used in
      the human facial bone area for the past 10 years. This article reviews the basic
      uses of distraction osteogenesis, the pros and cons, and possible future
      techniques.

PMID- 10079700
TI  - Outcomes data made easy.
AB  - Dx Index is a quick and easy method for quantifying patients' oral health. A
      number scale from 1 to 10 provides an easy-to-understand assessment of the dental
      health status of either an individual or a large group. During routine oral
      examinations, areas such as decayed teeth, pocket depth, inflammation and oral
      hygiene are numbered by level. Reading the lowest number on a chart pertaining to
      these categories gives a rapid overall score of dental health.

PMID- 10079701
TI  - The influence of neonatal nutrition on behavioral development: a critical
      appraisal.
AB  - Specific nutrients appear to modify the metabolism of neurotransmitters, which
      are endogenous regulators of neurogenesis, neural migration, and synaptogenesis
      during both embryonic and early postnatal life. This has led to the question of
      whether, by affecting neurotransmission, malnutrition during the early neonatal
      period affects behavioral development. The literature based on animal models
      suggests that nutrient deficiencies during early life influence neurotransmission
      and, in some instances, also affect behavioral outcomes. A clear answer to the
      question, however, remains elusive. This can be attributed to the complexity of
      the process of brain development, where changes at a cellular level may not
      necessarily translate into changes at a behavioral level. Future investigations
      in this important area of research should work toward refinement of the design of
      behavioral experiments so that these studies can contribute to the understanding
      of the putative mechanisms involved.

PMID- 10079702
TI  - Creatine: a dietary supplement and ergogenic aid.
AB  - Creatine is an amino acid that plays a vital role as creatine phosphate
      (phosphocreatine) in regenerating adenosine triphosphate in skeletal muscle to
      energize muscle contraction. Oral administration increases muscle stores. During
      the past decade, with notable popularity this past year, creatine has assumed
      prominence as an ergogenic aid for professional and elite athletes. Safety issues
      of long-term use, however, have not been addressed satisfactorily.

PMID- 10079703
TI  - Chronic alcohol intake interferes with retinoid metabolism and signaling.
AB  - Chronic and excessive ethanol consumption is associated with cellular
      proliferation, fibrosis, cirrhosis, and cancer of the liver. The critical event
      in early alcohol-induced hepatic injury is an alcohol-induced activation (cell
      proliferation and increased fibrogenesis) of hepatic stellate cells. However, the
      mechanisms by which alcohol causes proliferative activation in hepatic stellate
      cells have not been identified. An important characteristic of alcohol-induced
      injury is impaired vitamin A nutritional status. The demonstration that retinoic
      acid is the most physiologically active derivative of vitamin A and the discovery
      of retinoic acid receptors provide a mechanistic basis for understanding the
      actions of vitamin A and alcohol on hepatic cell proliferation. Recent studies
      have demonstrated that chronic alcohol intake can reduce hepatic retinoic acid
      concentrations, diminish retinoid signaling, and enhance activator protein-1 (AP
      1 (c-Jun and c-Fos)) expression in rat liver. These are the possible biochemical
      and molecular mechanisms whereby ethanol ingestion results in hepatic stellate
      cell proliferative activation and hepatic fibrogenesis.

PMID- 10079704
TI  - Vitamin D receptors: not just in the nucleus anymore.
AB  - Calcitriol, the active metabolite of vitamin D, is a steroid hormone that
      regulates calcium metabolism and cell differentiation by interacting with its
      nuclear receptor--the vitamin D receptor (VDR)--and by stimulating gene
      transcription. During the last decade, calcitriol also has been shown to
      stimulate rapid signal transduction pathways. This observation supports the
      hypothesis that a membrane-bound receptor similar to those that mediate peptide
      hormone biology exists. Recent research provides evidence for such a unique
      membrane VDR. Future research challenges are to integrate the membrane VDR into
      existing knowledge of vitamin D biology.

PMID- 10079705
TI  - High maternal body weight and pregnancy outcome.
AB  - Evidence of adverse perinatal outcomes among infants of obese pregnant women is
      confirmed by results of a large Swedish, population-based cohort study.
      Increasing maternal body weight was associated with perinatal mortality, although
      it protected against the delivery of a small-for-gestational-age infant.

PMID- 10079706
TI  - Are perceived professional qualities affected by knowledge of a counselor's
      sexual orientation?
AB  - The experimentally manipulated sexual orientation of a female counselor was not
      related to the perceptions of her Expertness, Attractiveness, or Trustworthiness
      rated by 8 male and 22 female, heterosexual college students.

PMID- 10079707
TI  - Amount of information on case illustrations in self-help psychology books.
AB  - 40 books on self-help psychology were examined in a 2 x 2 multivariate analysis
      of covariance design for the number of case illustrations, number of lines of
      text about case illustrations, and average number of lines per case illustration.
      The covariate was pages per book and the independent variables were status of the
      book (bestseller or nonbestseller) and decade of publication (1970-1979 or 1980
      1989). It was hypothesized that bestsellers would contain more case illustrations
      and lines of text describing case illustrations than nonbestsellers. Case
      illustrations per book in nonbestsellers increased significantly in number over
      the two decades when compared to bestsellers.

PMID- 10079708
TI  - Self-defeating personality and attachment revisited.
AB  - The present study showed for 98 adult men and 104 adult women that those who
      described their adult romantic attachments as secure were significantly less
      likely to have characteristics of the self-defeating personality than those who
      described their adult attachments as avoidant (p < 0.001) or anxious-ambivalent.
      The present results were consistent with those of two earlier studies with
      college-age subjects.

PMID- 10079709
TI  - Lifetime exposure to traumatic events among a sample of city bus drivers.
AB  - Lifetime exposure to traumatic events was assessed retrospectively among a
      representative sample of city bus drivers (228 men and 54 women) from Montreal,
      Canada. Among them, 68.1% reported at least one exposure to a traumatic event of
      any type. Among the 68% exposed. 70.4% reported multiple traumatic exposures (M =
      2.6, SD = 1.67), with ratings ranging from 0 to 12. This report underlines the
      fact that the prevalence of traumatic events is not yet well known.
      Epidemiological research should devote more effort to assess fully the lifetime
      prevalence of traumatic events and not only cases of PTSD.

PMID- 10079710
TI  - Sex differences in health attitudes and choice of health behaviors.
AB  - College students (82 men, 166 women) were assessed on a variety of physical
      fitness measures and completed questionnaires regarding health behaviors and
      attitudes. The men's health behaviors focused on physical activity while women's
      focused on dietary changes for better health.

PMID- 10079711
TI  - Age differences in death anxiety among African-American women.
AB  - Samples of 83 younger and 52 older African-American women completed a death
      anxiety scale; the younger women had significantly higher scores on the total
      scale, principally on items dealing with pain, loss of bodily integrity, and
      decomposition.

PMID- 10079712
TI  - A scale for assessing sleep hygiene: preliminary data.
AB  - No reliable measure exists for assessing the nature and scope of adherence or
      nonadherence to effective sleep hygiene practices. This report details the
      creation and empirical validation of the Sleep Hygiene Self-test. 52 combat
      veterans, patients in a treatment program for PTSD, completed the 30-item self
      test prior to and after their participation in 5 wks. of group therapy for sleep
      hygiene. Analysis indicated good internal consistency and suitability as a pre
      posttest measure.

PMID- 10079713
TI  - Preliminary validation and reliability of the Modified Child Dental Anxiety
      Scale.
AB  - An 8-question Modified Child Dental Anxiety Scale was developed to assess
      children's concerns about specific dental procedures. These dental situations
      include examination, scale and polish, injection, filling, extraction, and
      relative and general anaesthesia. A question about how the child felt generally
      when visiting the dentist was also included. Children (n = 314) from two schools
      in Liverpool, ages 8 to 15 years, completed a questionnaire including the
      modified scale, Corah's Dental Anxiety Scale, the Dental Fear Survey Schedule for
      Children, and background questions (age, sex and previous dental experience). The
      internal consistency was favourable (alpha = .84) and test-retest reliability
      acceptable. This initial study suggests that the scale may be useful in trials to
      assess the benefits of interventions to assist children receive dental treatment.

PMID- 10079714
TI  - Brain fag symptoms in rural South African secondary school pupils.
AB  - The study investigated brain fag symptoms in rural South African Secondary School
      pupils. The sample included 622 Grade 11, Secondary School pupils in the age
      range of 17 to 24 years (M age 19.3 yr., SD = 2.6) chosen at random from schools
      throughout the Northern Province of South Africa. A Cultural Orientation Scale, a
      Student Stress Scale, a General Self-efficacy Scale and Self-reporting
      Questionnaire were administered to collect data on socioeconomic status, cultural
      orientation, stress events, self-efficacy, perceived stress, "neurotic" disorder,
      and brain fag symptoms. Analysis indicated that 25% of the pupils suffered from
      the brain fag symptoms. There were positive significant relations for
      collectivism, socioeconomic status, female birth order, depression score on the
      Self-reporting Questionnaire, total score but not the anxiety score of the
      questionnaire with brain fag symptoms. This suggests the brain fag syndrome is
      basically a depressive disorder and to some extent an anxiety and depressive
      disorder. The findings are discussed in relation to the nature of brain fag
      symptoms, precipitating factors, and socioeconomic status.

PMID- 10079715
TI  - Fear of fat and the dream process: a correlational investigation.
AB  - Dream characteristics of 27 women from a graduate counseling program were
      correlated with the Goldfarb Fear of Fat Scale. Significant positive correlations
      were obtained for scores with recurrent nightmares (.38) and dreaming one is
      dreaming (.40). An inverse relationship was noted between sexual content of
      dreams and scores for fear of fat (-.41). Results were discussed in terms of
      associations among dissociation, body image, and the dream process.

PMID- 10079716
TI  - Love styles among Guatemalans in a local village.
AB  - 81 participants in a village in Guatemala were administered a translated version
      of the 1986 Love Attitudes Scale of Hendrick and Hendrick. Analysis showed that
      the men scored significantly higher on the Ludus love style than the women.
      Research among other Latinos outside the United States is suggested.

PMID- 10079717
TI  - Life after a myocardial infarction--the wives' point of view.
AB  - 37 wives of patients with myocardial infarction (MI) were interviewed after the
      index MI to examine the consequences with regard to quality of marital
      relationship, symptoms of distress, worries and concerns and to evaluate the long
      term outcome from the wives' personal point of view. The interviews were done at
      three times: during hospitalisation, three months after discharge, and 10 years
      post index MI. Our findings suggest relatively minor and time-limited adjustment
      problems concerning marital relationship and symptoms of distress. In a long-term
      perspective, only a few lasting changes were found. On the other hand, the wives'
      subjective assessment of the long-term effects of the infarct within different
      domains of life indicated that the illness episode had a comprehensive negative
      influence on their quality of life. In accordance with this, the majority
      reported that the myocardial infarction was still not a closed episode.

PMID- 10079718
TI  - Helpfulness of information sources in the selection of a nursing home.
AB  - 857 family members reported that visits and personal investigation at nursing
      homes as well as information from various people were more helpful than printed
      materials in selecting a nursing home.

PMID- 10079719
TI  - The Lie/Bet Questionnaire for screening pathological gamblers: a follow-up study.
AB  - This study follows up one in which was derived a two-item screening questionnaire
      for pathological gambling. In the previous study, the two-item screening
      questionnaire had sensitivity of .99 and specificity of .91. In this study,
      testing 295 men (116 pathological gamblers and 179 controls) and 128 women (30
      pathological gamblers and 98 controls), sensitivity was 1.00 and specificity .85.
      In the previous study, the predictive value of a positive result was .92 and of a
      negative result .99. In this sample, the predictive value of a positive result
      was .78 and of a negative result 1.00. These results indicate the two questions
      represent a useful screening device for a DSM-IV diagnosis of pathological
      gambling.

PMID- 10079720
TI  - Coping styles, anxiety, and depression in children.
AB  - Associations among scores on scales of anxiety and depression and a coping styles
      questionnaire were examined for 71 children. In general, correlations were
      positive, that is, high scores on anxiety and depression were accompanied by more
      frequent employment of all types of coping strategies.

PMID- 10079721
TI  - Effects of serial position on Bender-Gestalt errors using Koppitz's criteria.
AB  - The validity of the Koppitz Developmental scoring system in identifying organic
      impairment among functionally impaired adolescents was challenged in the current
      study. It was proposed that there are two distinct subtypes of errors in this
      system: those that are valid indicators of organic impairment (Category A) and
      those which are not but occur as a function of specific emotional factors
      (Category B). 46 male adolescents with a primary diagnosis of Conduct Disorder,
      Oppositional Defiant Disorder, or Attention-Deficit Hyperactivity Disorder were
      administered the Bender-Gestalt once using the standard order of administration
      and once in reverse order. It was hypothesized that more errors would be
      committed on cards presented later than those presented earlier in sequence for
      Category B but not Category A errors. Analysis provided partial support for this
      hypothesis.

PMID- 10079722
TI  - Introducing a new adolescent psychopathology screen: the High School Personality
      Questionnaire pathology section.
AB  - Evidence of criterion validity for a psychopathology supplement for the 1984 High
      School Personality Questionnaire of Cattell. Cattell, and Johns was obtained.
      This evidence came from correlations with Achenbach's scores on the Child
      Behavior Checklist and clinicians' ratings of 24 participants' psychological
      adjustment.

PMID- 10079723
TI  - Attitudes toward suicide among South African secondary school pupils.
AB  - This study investigated attitudes towards suicide among 622 Standard 9 (U.S.
      Grade 11) secondary school pupils chosen at random from schools throughout the
      Northern Province in South Africa. The pupils were 254 (41%) boys and 368 (59%)
      girls in the age range of 17 to 24 years, with a mean age of 19.3 yr. A
      questionnaire was administered to obtain data on attitudes and other measures.
      There were 31 (17%) parasuicidal boys and 34 (13%) girls. Major intentions or
      reasons to commit suicide mentioned were "failing to solve problems" and "mental
      illness." Most frequent possible suicide methods were firearms, pills, or poison.
      Significant associations were found with having a friend or relative who
      committed suicide, parasuicide (oneself), depression, stress events, ethnicity,
      and attitudes towards suicide.

PMID- 10079724
TI  - The changing face of MMPI practice.
AB  - To assess the status of changing MMPI practice a questionnaire was sent by mail
      to 368 licensed psychologists in Kansas with a 40% response rate (N = 147). The
      modal respondent had 14.2 yr. of experience. Virtually all reported that they
      currently used the MMPI: 37.0% reported using the MMPI, 80.1% MMPI-2, and 40.4%
      MMPI-A. A majority (67.6%) used computerized scoring with local scoring used by
      three out of four respondents. Computerized administration was used by 15.9% and
      computerized interpretation by 43.8%. Most used both High Point Codes (91%) and
      Elevation (84.7%) for interpretations. Two of three respondents thought that the
      High Point Codes and Elevations for the MMPI and MMPI-2 are related. The results
      of this survey of current practice suggest that many practitioners may be making
      false assumptions about the nature of the MMPI-2 and MMPI-A and their
      relationships with the original MMPI. If the MMPI is to retain its hard-fought
      presence as a diagnostic, forensic, and selection tool, we must pay greater
      attention to these issues.

PMID- 10079725
TI  - Stability of the MCMI-III in a substance-abusing inpatient sample.
AB  - The stability of the MCMI-III personality disorder and clinical syndrome scales
      was assessed in a substance-abusing inpatient sample of 35 African-American men
      over an average test-retest interval of 6 mo. Estimates were higher for the
      personality pattern scales than for the clinical syndrome scales. The Dependent
      personality pattern scale (.83) and the Narcissistic personality pattern scale
      (.80) were reliable after about six months, whereas Drug Abuse, Somatoform, and
      Major Depression showed lower stability. As in previous research using the MCMI
      I/II, estimates were lower than those reported in the test manual.

PMID- 10079726
TI  - Depression and attribution in abused children and their nonoffending caregivers.
AB  - This study examined depression and attribution in 17 abused children and their
      nonoffending caregivers. Analysis indicated that negative attributions were
      significantly related to higher scores on depression of both children and
      caregivers, that depression scores of caregivers were unrelated to depression of
      their abused children, but that caregivers, nevertheless, assessed their
      children's self-reported depression as similar to their own self-reported
      depression.

PMID- 10079727
TI  - Regular and occasional smoking by college students: personality attributions of
      smokers and nonsmokers.
AB  - Recent reports show an increase in smoking among college students and suggest
      that occasional smoking is now initiated by previously nonsmoking students. This
      study evaluated whether this apparent increase in smoking by students is
      associated with positive self-images associated with smoking. Regular and
      occasional smokers rated how smoking "changes the way you feel about yourself" on
      18 self-attributes that may be associated with smoking, e.g., from cigarette
      advertisements. Nonsmokers also rated smokers on the same 18 attributes. All
      three groups rated three attributes in the negative direction with at least a
      moderate effect size: that being a smoker was less healthy, that smokers were
      less desirable as a date and that smokers were less attractive while smoking. On
      only one other attribute regular smokers differed from neutral with at least a
      moderate effect size: that smoking made them feel less feminine. As hypothesized,
      the occasional smokers also rated some attributions positively with at least a
      moderate effect size: that smoking made them feel more daring and more
      adventurous and did not make them feel like an outcast. The nonsmokers rated a
      number of additional attributes about smokers negatively with at least a moderate
      effect size: that smokers are less sexy, less feminine, less sophisticated, less
      masculine, and less mature. Thus, the results suggest that smoking shows at best
      mixed associations with self-attributions of college students who smoke and is
      viewed negatively by those who do not smoke. Other results suggest that the
      recent increase in occasional smoking may be related to smoking with friends who
      smoke and smoking while drinking alcohol.

PMID- 10079728
TI  - Ranking of romantic acts among Cape Verdean and Portuguese students.
AB  - College students, 119 men and 116 women, from Cape Verde and Portugal ranked the
      importance of romantic acts. Comparisons between men and women and between Cape
      Verdean and Portuguese students showed no significant differences. An interesting
      finding was that "making love" was ranked the most important romantic act by men
      but only fifth by women in Portugal (behind cuddling, gazing, love letters, and
      kissing), whereas it was ranked third for both sexes in Cape Verde.

PMID- 10079729
TI  - Personality and defenses: a cross-cultural study of psychiatric patients and
      healthy individuals in Nicaragua and Sweden.
AB  - This study examined cross-cultural variability in personality and defenses among
      Nicaraguan and Swedish healthy individuals, patients with borderline personality
      disorder and schizophrenic disorders by means of the projective perceptual
      Defense Mechanism Test. The over-all aim was to test the hypothesis proposed by
      Anthony Marsella of 'severity related cross-cultural variability' suggesting that
      differences in symptom profile or personality patterns between cultures are most
      pronounced among healthy individuals and less so among individuals with severe
      mental disorders as they are perceived as more universal and less culturally
      determined. The over-all results showed that cross-cultural differences were in
      accordance with the proposed hypothesis. In addition, there were significant
      intracultural differences between the different diagnostic groups in both
      countries. The conclusion is that the Defense Mechanism Test and Partial Least
      Squares analysis seem to be powerful methods for personality assessment and
      potentially for cross-cultural research, and culture-specific norms in the
      Defense Mechanism Test must be employed.

PMID- 10079730
TI  - A neglected window on hypothesis testing in adolescence: explicit standard order
      conditional selection tasks.
AB  - The paper reported four experiments on explicit standard order conditional
      selection tasks, which permit more direct inference of subjects' strategies than
      do other conditional selection tasks. The experiments allowed plausible rational
      support-seeking strategies to be reduced from nine to three, disproof strategies
      from six to three. The main strategy in early adolescence was either (1) models
      based deduction, as suggested by Johnson-Laird and Byrne in 1991 or (2) rules
      based deduction, as suggested by Rips in 1994, with a factual attitude to
      hypothesis and offered information. In late adolescence a substantial minority
      adopt a hypothetical attitude to both these things, which may be applied with
      either of these strategies or with (3) the nondeductive strategy suggested by
      Langford and Hunting in 1994. This general picture of developmental possibilities
      can be extended to Inhelder's and Piaget's problems requiring information search
      to test conditional and biconditional hypotheses, in particular their chemicals,
      pendulum, and rods problems. This extension is obtained by assuming that
      adolescents acquire a range of strategies for problems requiring more or less
      focussed information search, conditional selection tasks requiring the former,
      Piagetian formal operations tasks tending towards the latter. Current evidence
      does not indicate whether strategies (1) or (2) are dominant in younger
      adolescents or whether strategies (1) or (2) or (3) are dominant in older
      adolescents. Thus, the Piagetian argument that formal operations thinking passes
      from factual rules-based deduction to hypothetical rules-based deduction is only
      one of several styles of theory that can readily accommodate current evidence in
      this area.

PMID- 10079731
TI  - The existential vacuum in treating substance-related disorders.
AB  - Clients in treatment for substance-related disorders are excellent candidates for
      discussing Frankl's concept of the existential vacuum as such people fill their
      existential vacuum with alcohol and other drugs. A keen therapist can make this
      connection and help clients fill their voids with meaningful activities.

PMID- 10079732
TI  - Fear as a correlate of authoritarianism.
AB  - A preliminary study investigating the relationship between authoritarianism and
      self-reported fear was conducted. Significant correlations were found between
      scores on the Right-Wing Authoritarianism Scale and the Fear Perception Index.
      Theoretical explanations for the relationship were explored using assumptions
      drawn from evolutionary psychology.

PMID- 10079733
TI  - Modeling precognitive dreams as meaningful coincidences.
AB  - 50 college students completed the Anomalous Experiences Inventory, the AT-20
      measure of tolerance of ambiguity, and a frequency of dream recall questionnaire.
      Using path analysis we show that precognitive dreams can be modeled as accidental
      'hits' with increased dream recall and the interpretation of such hits as
      'meaningful coincidences' seems facilitated by a belief in the paranormal. As
      predicted, both factors are affected by tolerance of ambiguity, which provides
      the flexibility required to store and recall ambiguous dream information while
      simultaneously allowing dream recallers to assume a paranormal origin of their
      'precognitive' dreams. Moreover, the fit of the proposed model did not depend on
      sex or age. Alternative models that provided a better fit to the data validated
      the roles of tolerance of ambiguity and belief in the paranormal in eliciting
      experiences of precognitive dreaming, but frequency of dream recall was not
      confirmed as a crucial factor.

PMID- 10079734
TI  - Incarcerated women: I. A comparison of college and noncollege inmates.
AB  - Whether inmates who participate in college programs have better postrelease
      outcomes than those who do not participate is controversial, with opponents of
      college prison programs suggesting that college programs' successes are due to
      selectivity. 150 women in a state prison, including 61 women in a college program
      and 89 women sampled from the general population, were compared. Only 7 of 34
      variables significantly differentiated the two groups. The percentage of women
      who had used marijuana, rates of mothers' arrests, length of time served, rates
      of physical abuse, participation in vocational programs, and percent incarcerated
      for violent offences were higher among the women in the college program, who were
      more likely to be first-time offenders.

PMID- 10079735
TI  - Word-association patterns of mental hospital patients.
AB  - The present study concerned an attempt to corroborate the classic findings of
      Rapaport, Gill, and Schafer in distinguishing mental hospital patients from
      control subjects, using a new objectively scored word-association test. 12
      computer-scored objective scales were used to compare groups of 101 mental
      hospital inpatients (n = 75, including 37 on a prison ward) and outpatients (n =
      26) and 101 control subjects matched with the patients for sex, age, racial and
      ethnic status, and education. A stepwise multiple discrimination analysis of the
      scores on the 12 scales of the test significantly distinguished the groups.
      Scales weighted most highly were Masochism, Antonyms, and Aggression. Subsequent
      t tests suggested that control subjects scored higher on Aggression, Self
      reference, and Masochism scales, whereas patients scored higher on Rejections
      (nonresponses to stimulus words). Of these, only Self-reference and Rejections
      were items identified by Rapaport, et al.

PMID- 10079736
TI  - Drug use among African Americans: ethnic identity as a protective factor.
AB  - This study examined the multiple components of ethnic identity, the place of this
      ethnic identity set in the mediational model of the path to drug use predicted by
      our family interactional framework, and the protective role of each component of
      ethnic identity. The participants were 259 male and 368 female African Americans
      in late adolescence. They responded to a structured questionnaire in individual
      interviews. We found that few of the specific components of ethnic identity were
      significantly related as main effects to drug use. Most of the effect of ethnic
      identity was mediated by the family set of variables. Each of the components of
      ethnic identity offset risks or enhanced protective factors from the ecology,
      family, personality, and peer domains, thereby lessening drug use. This pattern
      highlights the importance of incorporating ethnic identity into drug prevention
      programs which serve African-American youth.

PMID- 10079737
TI  - The Fagerstrom Test for Nicotine Dependence in a Spanish sample.
AB  - The Fagerstrom Test for Nicotine Dependence was developed to improve the
      reliability and validity of the Fagerstrom Tolerance Questionnaire. In this
      study, we examined the applicability of the Spanish version of such test as well
      as its relationship to sex, age, and consumption of cigarettes, in a
      representative sample of smokers from Galicia, Spain (N = 646).

PMID- 10079738
TI  - Reliability of the Arabic Obsessive-Compulsive Scale in Kuwaiti and American
      students.
AB  - The Arabic Obsessive-Compulsive Scale was administered to 204 Kuwaiti and 132
      American college students. The Spearman-Brown reliabilities were, respectively
      .77 and .82, while Cronbach alphas were .76 and .82, denoting acceptable values
      for the two samples.

PMID- 10079739
TI  - [The impact of antimicrobial resistance and Streptococcus pneumoniae serotype
      distribution on the mortality of children under 5 years of age with invasive
      disease].
AB  - Severe pneumonia and meningitis caused by Streptococcus pneumoniae have been
      persistently associated with high mortality rates, despite advances in
      antimicrobial therapy and the development of vaccines. Resistance to penicillin
      and other antimicrobial agents is increasing and spreading worldwide. Even though
      risk factors for development of antimicrobial resistance have been identified,
      their influence on mortality has not been clarified. With regard to virulence,
      differences among serotypes have been determined, but their impact on mortality
      is unknown. The aim of this study was to determine the risk factors associated
      with mortality in children with invasive pneumococcal disease. Clinical records
      for 245 children under 5 years of age with invasive disease due to S.pneumoniae
      were reviewed. Children were diagnosed between 1994 and 1996 in Colombia, during
      the study of S.pneumoniae capsular types conducted by the Pan American Health
      Organization's Regional System for Vaccines. Of the 245 patients whose charts
      were examined, 29 (11%) died. No significant differences in age, gender,
      underlying disease, nor antimicrobial treatment concordance were found. Variables
      associated with mortality in the univariate analysis were a diagnosis of
      meningitis; antimicrobial resistance to penicillin, trimethoprim-sulfamethoxazole
      (TMS), or erythromycin; multiresistance, and serotypes 6, 23F, 7F, 8, and 35B. In
      the logistic regression, serotypes 7F (OR = 7.13; P = 0.04) and 8 (OR = 13.8; P =
      0.07), polipnea (OR = 2.74; P = 0.03), meningitis (OR = 5.02; P = 0.0001) and TMS
      resistance (OR = 2.62; P = 0.02) continued to be associated with mortality. In
      patients with pneumonia, serotype was the factor most consistently associated
      with mortality; in meningitis patients, it was antimicrobial resistance.
      Differences in mortality according to serotype must be taken into account in
      developing a vaccine if a substantial impact on pneumococcal disease morbidity
      and mortality is to be achieved.

PMID- 10079740
TI  - Efficiency of hospital cholera treatment in Ecuador.
AB  - This study analyzed the efficiency of cholera treatment in three hospitals
      representative of the Ecuadorian public health system in order to provide
      hospital directors and administrators and health service policy-makers with
      information to plan responses to future epidemics and to reduce the costs of
      cholera treatment in general. For the study, total and excess cholera treatment
      costs were calculated using hospital files and statistics and an in-hospital
      surveillance system of the cholera cases. The type and quantity of each input
      used for each treatment were analyzed, as well as the number of days
      hospitalized, according to the severity of the illness. With this process, excess
      costs were determined in relation to a "treatment norm" that would have been
      appropriate for each patient. The researchers found that 45% of the cholera
      treatment costs were excessive. The most important contributor was excess
      recurrent costs (90%), including extended hospital stays, disproportionate use of
      intravenous rehydration solutions, and unnecessary laboratory tests. Excess
      capital costs, from land, buildings, and hospital equipment, represented 10% of
      the total excess treatment costs. No significant relationship was found between
      treatment costs and the severity of the illness, nor between costs and a
      patient's age. A patient's sex appeared to be an important variable, with the
      cost of treating women being notably higher than for men. An inverse relationship
      was found between treatment costs and the complexity of the hospital. The
      researchers concluded there was an inefficient use of resources in the treatment
      of cholera in the three hospitals where the research was performed.

PMID- 10079741
TI  - [Association between household solid waste disposal and health, Belo Horizonte
      (MG), Brasil].
AB  - There are few published studies about the effects of inadequate solid waste
      collection on the health of the population exposed to this situation. The
      objective of the present work was to describe this association in a sample of
      children under 5 years of age living in seven low-income neighborhoods and
      favelas in the city of Belo Horizonte, state of Minas Gerais, Brazil. We defined
      as "exposed" those children whose families were not served by waste collection;
      "not-exposed" were children who lived in areas with waste collection. The study
      employed data collected in 1994 and organized as a database by the municipal
      department of health. We employed a cross-sectional design, in which a "case" was
      defined as a child whose outpatient clinic record indicated a diagnosis of
      diarrheal, parasitic, or dermatological disease. Other diagnoses for the same age
      group composed the control group. Our epidemiological study revealed an
      association between the absence of domestic solid waste collection and public
      health. Our results suggest that the children exposed to the absence of solid
      waste collection have a 40% higher odds (OR = 1.40) of presenting diarrheal,
      parasitic, and dermatological diseases than not-exposed children. In addition,
      the calculation of attributable risk revealed that the presence of waste
      collection could prevent (based on the 1995 situation) 512 cases in the
      neighborhoods studied and (based on the 1994 conditions) 2316 cases among
      children in the entire city of Belo Horizonte.

PMID- 10079742
TI  - [Antibodies against Trichinella spiralis in the rural population of the Province
      of Cordillera, Bolivia].
AB  - A seroepidemiological study was conducted to determine the prevalence of
      antibodies to Trichinella spiralis among rural residents of Cordillera province,
      Santa Cruz Department, Bolivia. Using the enzyme-linked immunosorbent assay
      (ELISA), 234 serum samples were examined, and antibodies were detected in seven
      of the samples (3%). The results document for the first time the presence of
      human infestation with Trichinella in Bolivia and suggest the need to strengthen
      trichinelosis surveillance in the municipal slaughterhouses, to prevent the
      clandestine slaughter of animals, and particularly to ensure that residents and
      meat producers in the area become aware of the dangers of this zoonosis.

PMID- 10079743
TI  - Absence of impact of aerial malathion treatment on Aedes aegypti during a dengue
      outbreak in Kingston, Jamaica.
AB  - During an outbreak of dengue fever in Jamaica from October to December 1995, a
      study was carried out to determine the impact of aerial ultra-low volume
      malathion treatment on adult Aedes aegypti. This was done by monitoring
      oviposition rates of the vector in three urban communities in Kingston and by
      exposing caged mosquitoes both directly and indirectly to the aerial malathion
      treatment. The insecticide was delivered at a rate of 219 mL/ha between 7:10 a.m.
      and 8:45 a.m. The results of the study clearly showed that the insecticide
      application was ineffective in interfering with Aedes aegypti oviposition, and
      adult mosquitoes held in cages inside dwellings were largely unaffected.
      Consequently, this type of intervention seemed to have little significant impact
      in arresting or abating dengue transmission.

PMID- 10079744
TI  - [Participation of dental auxiliary personnel in local health systems].
AB  - Though numerous local health systems (sistemas locales de salud, or SILOS) in
      Brazil employ dental assistants, there is little information on the contributions
      these workers make to oral health programs. The purpose of this study was to
      examine the role of such workers in 10 SILOS in five municipalities in the state
      of Sao Paulo. Of the 325 dental assistants and dental hygienists employed in
      those systems, 245 (75.4%) answered a questionnaire that had been prepared. The
      results showed variations in the degree to which dental assistants participated
      in oral health promotion activities in the SILOS studied. In some SILOS, these
      workers devoted more time to dental health promotion activities than to helping
      perform dental tasks with individual patients. The most frequent oral health
      promotion activities were fluoride rinses, plaque detection followed by
      supervised brushing, and educational activities at basic health units and
      schools. In all cases, dental assistants working in the SILOS played a
      significant role in helping transform the practice of dentistry within the sphere
      of public health.

PMID- 10079745
TI  - [Management and performance of human resources in reproductive health services].
AB  - For most people, utilizing reproductive health services is colored by strong
      emotional and subjective implications. Therefore, it is essential to know the
      local situation well when planning those services and designing activities
      directed toward the community. User satisfaction also depends on allowing those
      persons to participate in solving problems from their own perspective and on the
      treatment they receive from health service personnel. It's impossible to
      overstate the importance of the performance of health care providers and,
      accordingly, the management of those personnel. This article presents general
      principles that govern such management, the tasks that management entails, and
      the most desirable attitudes in reproductive health service providers.

PMID- 10079746
TI  - Impact of latest OIG compliance guidelines on physician billing practices.

PMID- 10079748
TI  - Loss prevention case of the month. Possible vs. appropriate.

PMID- 10079747
TI  - Health insurance: does it affect health?

PMID- 10079749
TI  - Replacing the company doctor: Pruden Valley, Tennessee, and the development of
      the miners' clinics.

PMID- 10079750
TI  - Oral-facial sports injuries.

PMID- 10079751
TI  - A 30-year-old man with hypopituitarism.

PMID- 10079752
TI  - Influenza in the world.

PMID- 10079753
TI  - Influenza.

PMID- 10079754
TI  - Recommended composition of influenza virus vaccines for use in the 1999-2000
      season.

PMID- 10079756
TI  - Evaluation of certain food additives and contaminants. Forty-ninth report of the
      Joint FAO/WHO Expert Committee on Food Additives.
AB  - This report presents the conclusions of a Joint FAO/WHO Expert Committee convened
      to evaluate the safety of various food additives and contaminants, with a view to
      recommending acceptable daily intakes for humans, and to prepare specifications
      for the identity and purity of food additives. The first part of the report
      contains a general discussion of the principles governing the toxicological
      evaluation of food additives and contaminants, including flavouring agents, and
      the establishment and revision of specifications, with comments concerning limits
      for arsenic, lead and other heavy metals, and enzymes derived from genetically
      manipulated organisms. A summary follows of the Committee's evaluations of
      toxicological data on various specific food additives (tert-butylhydroquinone
      (TBHQ), microcrystalline cellulose, sucrose esters of fatty acids and
      sucroglycerides, alpha-acetolactate decarboxylase, maltogenic amylase, trans
      anethole, hydrogenated poly-1-decene and maltitol syrup), food ingredients (short
      and long-chain acyltriglycerides), flavouring agents and the contaminants
      aflatoxins. Annexed to the report are tables summarizing the Committee's
      recommendations for acceptable daily intakes of the food additives and food
      ingredients considered, changes in the status of specifications for these
      substances and specific flavouring agents, and further toxicological studies
      required.

PMID- 10079757
TI  - Cell separation on microfabricated electrodes using
      dielectrophoretic/gravitational field-flow fractionation.
AB  - Dielectrophoretic/gravitational field-flow fractionation (DEP/G-FFF) was used to
      separate cultured human breast cancer MDA-435 cells from normal blood cells mixed
      together in a sucrose/dextrose medium. An array of microfabricated,
      interdigitated electrodes of 50 microns widths and spacings, and lining the
      bottom surface of a thin chamber (0.42 mm H x 25 mm W x 300 mm L), was used to
      generate DEP forces that levitated the cells. A 10-microL cell mixture sample
      containing approximately 50,000 cells was introduced into the chamber, and
      cancerous and normal blood cells were levitated to different heights according to
      the balance of DEP and gravitational forces. The cells at different heights were
      transported at different velocities under the influence of a parabolic flow
      profile that was established in the chamber and were thereby separated.
      Separation performance depended on the frequency and voltage of the applied DEP
      field and the fluid-flow rate. It took as little as 5 min to achieve cell
      separation. An analysis of the DEP/G-FFF results revealed that the separation
      exploited the difference in dielectric and density properties between cell
      populations. The DEP/G-FFF technique is potentially applicable to many biological
      and biomedical problems, especially those related to microfluidic systems.

PMID- 10079758
TI  - Use of vapor-phase acid hydrolysis for mass spectrometric peptide mapping and
      protein identification.
AB  - A method for mass spectrometric peptide mapping was developed, based on
      hydrolysis of a solid protein by acid vapor followed by mass spectrometric
      analysis of the cleavage products. The method is applicable to lyophilized
      samples as well as proteins present in gels after separation by SDS-PAGE. The
      cleavage specificity was established using a number of standard proteins. Three
      different types of cleavages were observed: specific internal backbone cleavages
      at Asp, Ser, Thr, and Gly and N- and C-terminal sequence ladders. On the basis of
      the observed cleavage characteristics, a strategy for protein identification
      based on the peptide mass maps was developed. The identification strategy
      utilizes the specific internal backbone cleavages as well as the partial sequence
      information, obtained from the sequence ladders.

PMID- 10079759
TI  - Evidence for kinetic inhomogeneity in the curing of epoxy using the near-infrared
      multispectral imaging technique.
AB  - The kinetics of curing of an epoxy resin by amine was studied using a near
      infrared (NIR) multispectral imaging spectrometer. This imaging spectrometer is
      capable of sensitively and rapidly recording NIR spectral images of a sample
      because it was constructed with an acousto-optic tunable filter and an InGaAs
      focal plane array NIR camera. The high sensitivity and fast scanning ability of
      the spectrometer make it suitable for kinetic determination of fast reactions.
      Additionally, it has features that conventional NIR spectrometers cannot offer,
      namely, its ability to provide kinetic information at different positions within
      a sample. Furthermore, the high spatial resolution and sensitivity of the InGaAs
      camera make it possible to determine the kinetics from data collected by a single
      pixel in the camera. The kinetics of curing of epoxy by amine, determined by this
      multispectral imaging instrument, show that the reaction rates within the sample
      are very inhomogeneous. Because of this kinetic inhomogeneity, differences in the
      degrees of cure at different positions within the sample can be as high as 37%
      when data from only a single pixel were used for calculation. The inhomogeneity
      was not be observed if an average of a large number of pixels were used.

PMID- 10079760
TI  - Detection of peptides by precolumn derivatization with biuret reagent and
      preconcentration on capillary liquid chromatography columns with electrochemical
      detection.
AB  - The separation and detection of biuret complexes of neuropeptides by capillary
      liquid chromatography with electrochemical detection was explored. Capillaries of
      25-micron inner diameter packed with base-resistant, polymer-based reversed-phase
      particles were used for separation, and C-fiber electrodes were used for
      detection. Detection at the C-fiber electrode was found to have some differences
      in relative sensitivity for peptides compared to glassy carbon electrodes used
      previously. On-column preconcentration of preformed complexes allowed up to 1
      microL samples to be injected with minimal band broadening resulting in a 100
      fold improvement in concentration detection limit with no effect on mass
      detection limit. Concentration detection limits ranged from 5 to 59 pM, depending
      upon the peptide, corresponding to 5-59 amol injected. The low concentration
      detection limit was possible because of minimal baseline disturbances, minimal
      formation of unwanted products, and high efficiency of complex formation
      associated with biuret derivatization. The method was applied to determination of
      vasopressin and bradykinin in dialysates collected with 5-min sampling frequency
      from the rat supraoptic nucleus.

PMID- 10079761
TI  - Cross-linking of 17 beta-estradiol to monoclonal antibodies by direct UV
      irradiation: application to an enzyme immunometric assay.
AB  - Ultraviolet irradiation was used to cross-link 17 beta-estradiol directly to
      monoclonal anti-17 beta-estradiol antibodies coated on 96-well microtiter plates.
      Cross-linking efficiency was directly correlated with both irradiation energy and
      wave-length. The best results were obtained at 254 (10 J/cm2, 45-min irradiation)
      and 312 nm (40 J/cm2, 160-min irradiation). The irradiation fully denatured both
      individual molecules (i.e., 17 beta-estradiol and monoclonal anti-17 beta
      estradiol antibody), but 17 beta-estradiol was at least partly protected when
      immunologically bound to the paratope of the antibody. Four different monoclonal
      anti-17 beta-estradiol antibodies yielded positive results, demonstrating that
      this photo-cross-linking has considerable potential. We used this original
      approach to develop a new enzyme immunometric assay of 17 beta-estradiol based on
      our previously described immunometric procedure, solid-phase immobilized epitope
      immunoassay, which uses chemical agents to cross-link haptens via amino groups to
      specific antibodies. The assay was specific (no cross-reactivity with other
      natural steroids), precise, and sensitive (detection limit of 38 pg/mL in human
      serum). It correlated well with two competitive commercial immunoassays when
      tested on 40 human sera.

PMID- 10079762
TI  - Double-disk solid-phase extraction: simultaneous cleanup and trace enrichment of
      herbicides and metabolites from environmental samples.
AB  - Phenylurea and triazine herbicides, including some metabolites, were isolated
      from water and soil extracts by solid-phase extraction using a layered system of
      two extraction disks, a method called double-disk solid-phase extraction. The
      first disk consisted of strong anion exchange (SAX) of 10-micron styrene
      divinylbenzene (SDB) particles embedded in Teflon, and the second disk was a C18
      disk of 10-micron particles also embedded in Teflon. A volume of 500 mL of water
      or aqueous soil extract is passed through the layered system with the SAX disk
      first. The purpose of the SAX disk is to remove the humic and fulvic acids from
      the water or aqueous soil extract by ion exchange through their carboxyl groups.
      Even during methanol elution of herbicides, the humic substances remain bound to
      the SAX disk with > 85% retention. Elution with methanol results in more than 90%
      recovery of the herbicides from the layered extraction disks. Removal of the
      humic and fulvic acids results in greater sensitivity for diode array detection
      quantitation (0.05 micrograms/L for herbicides) by substantially reducing the
      absorbance of the humic peak on the LC chromatogram. The herbicides adsorb to the
      SAX disk either through hydrogen bonding to the anion-exchange sites or by
      hydrophobic interaction with the SDB surface of the anion-exchange disk. The
      method was tested for the analysis of natural water samples from the Mississippi
      Embayment, a cotton-growing area of the southeastern United States.

PMID- 10079763
TI  - Field method for the determination of hexavalent chromium by ultrasonication and
      strong anion-exchange solid-phase extraction.
AB  - A simple, fast, sensitive, and economical field method was developed and
      evaluated for the determination of hexavalent chromium (CrVI) in environmental
      and workplace air samples. By means of ultrasonic extraction in combination with
      a strong anion-exchange solid-phase extraction (SAE-SPE) technique, the
      filtration, isolation, and determination of CrVI in the presence of trivalent
      chromium (CrIII) and potential interferents was achieved. The method entails (1)
      ultrasonication in basic ammonium buffer solution to extract CrVI from
      environmental matrixes; (2) SAE-SPE to separate CrVI from CrIII and
      interferences; (3) elution/acidification of the eluate; (4) complexation of
      chromium with 1,5-diphenylcarbazide; and (5) spectrophotometric determination of
      the colored chromium-diphenylcarbazone complex. Several critical parameters were
      optimized in order to effect the extraction of both soluble (K2CrO4) and
      insoluble (PbCrO4) forms of CrVI without inducing CrIII oxidation or CrVI
      reduction. The method allowed for the dissolution and purification of CrVI from
      environmental and workplace air sample matrixes for up to 24 samples
      simultaneously in less than 90 min (including ultrasonication). The results
      demonstrated that the method was simple, fast, quantitative, and sufficiently
      sensitive for the determination of occupational exposures of CrVI. The method is
      applicable for on-site monitoring of CrVI in environmental and industrial hygiene
      samples.

PMID- 10079764
TI  - Amperometric determination of total cholesterol at gold electrodes covalently
      modified with cholesterol oxidase and cholesterol esterase with use of thionin as
      an electron mediator.
AB  - Immobilization of cholesterol oxidase (EC 1.1.3.6) (ChOx) on a gold electrode was
      attempted by cross-linking using glutaraldehyde between ChOx molecules and a self
      assembled monolayer of 2-aminoethanethiolate. The resulting electrode (ChOx/Au)
      exhibits an amperometric response to free cholesterol in the presence of thionin
      as an electron mediator, and a steady-state response is obtained approximately 60
      s after injection of cholesterol into the electrolyte solution. Coimmobilization
      of cholesterol esterase (EC 3.1.1.13) (ChE) and ChOx (ChE/ChOx/Au) allows the
      amperometric determination of both esterified cholesterol and free cholesterol.
      Cyclic voltammetry of the ChE/ChOx/Au and the dependence of the amperometric
      response to cholesterol on the concentration of thionin suggest that thionin is
      encapsulated in the enzyme film on the electrode surface. Apparent Michaelis
      constants of the ChOx/Au and the ChE/ChOx/Au electrodes suggest that the
      amperometric response was controlled by penetration of the reaction substrate
      into the films of the enzyme(s). The concentration of total (free and esterified)
      cholesterol in human serum samples, determined by using the techniques developed
      in the present study, is in good agreement with that determined by the well
      established technique using colorimetry.

PMID- 10079765
TI  - Use of erythrocyte ghosts for preconcentration in element speciation.
AB  - A totally new biosorption concept has been tested. It involves the use of a
      biological membrane with given transport characteristics that encloses a reaction
      compartment chosen to bind incorporated substances irreversibly. Such a system is
      an erythrocyte ghost: erythrocytes that are hypotonically lysed can be filled
      with the desired media and resealed by warming up for 1 h. The transport system
      exploited is the predominant one in erythrocytes, i.e., the anion transport
      system with 10(6) channels/cell. Erythrocyte ghosts (in the following simply
      called ghosts) filled with ascorbate or cysteine as intracellular reductants were
      compared to unmodified human erythrocytes with regard to their ability to
      accumulate chromate specifically. Furthermore, the lifetime and behavior of the
      ghosts with respect to the influence of extracellular Cr(III) were tested. The
      great similarity found between the ghosts tested and unmodified erythrocytes
      clearly shows the general applicability of this new biosorption concept which
      offers possibilities for the biosorption of analytes that cannot be accumulated
      by unmodified erythrocytes.

PMID- 10079766
TI  - Two-layer sample preparation: a method for MALDI-MS analysis of complex peptide
      and protein mixtures.
AB  - The analytical performance of matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry for direct analysis of peptide and protein mixtures is strongly
      dependent on the sample and matrix preparation. A two-layer sample preparation
      method is demonstrated to be very effective for analyzing complex mixtures. In
      this method, the first layer on the MALDI probe is the densely packed matrix
      microcrystals formed by fast solvent evaporation of a matrix solution. A mixture
      solution containing both matrix and sample is then deposited onto the first layer
      to form uniform analyte/matrix micrococrystals. It is found that the addition of
      matrix to the second-layer sample solution proves to be critical in analyzing
      mixtures of peptides and proteins covering a broad mass range. The effect of
      solvent conditions for preparing the second-layer solution is discussed. The
      application of this method is demonstrated for the analysis of cow's milk where
      milk proteins as well as peptide fragments produced from proteins by indigenous
      proteinases are detected. Direct analyses of peptides and proteins from a
      bacteria extract and crude egg white are also illustrated.

PMID- 10079767
TI  - An nmr conformational analysis of a synthetic peptide Cn2(1-15)NH2-S-S-acetyl
      Cn2(52-66)NH2 from the New World Centruroides noxius 2 (Cn2) scorpion toxin:
      comparison of the structure with those of the Centruroides scorpion toxins.
AB  - The solution structure of a synthetic peptide, Cn2(1-15)NH2-S-S-acetyl-Cn2(52
      66)NH2 from toxin 2 (Cn2) of the New World scorpion Centruroides noxius was
      determined using nmr and molecular dynamics calculations. The peptide has no
      significant secondary structure such as an alpha-helix or a beta-sheet, yet it
      has a fixed conformation for the first chain. The backbone secondary structure
      involving residues 6-12 in this peptide shows an excellent overlap with the
      structures of natural neurotoxins from Centruroides sculpturatus Ewing. Residues
      6-9 form a distorted type I beta-turn and residues 10-12 form a gamma-turn. As
      residues 7-10 in the Centruroides toxins correspond to one of the regions of
      highest sequence variability, it may account for the species specificity and/or
      selectivity of toxic action. The conformation of this region evidently plays an
      important role in receptor recognition and in binding to the neutralizing
      monoclonal antibody BCF2 raised against the intact toxin.

PMID- 10079768
TI  - Structural consequences of D-amino acids in collagen triple-helical peptides.
AB  - The effects of racemization of aspartic acid on triple-helical formation have
      been studied using a "host-guest" peptide approach where selected guest Gly-Xaa
      Yaa triplets were included within a common acetyl-(Gly-Pro-Hyp)3-Gly-Xaa-Yaa-(Gly
      Pro-Hyp)4-Gly-Gly-amide frame-work. Four guest triplets, Gly-Asp-Hyp and Gly-Asp
      Ala where Asp is either L-Asp or D-Asp were studied. Thermal stability data
      indicated that incorporation of D-Asp residues prevented triple-helix formation
      in phosphate buffered saline, although triple-helical structures were formed in a
      stabilizing solvent, 67% aqueous ethylene glycol. In this solvent the melting
      temperatures of D-Asp containing peptides were more than 30 degrees C lower than
      the corresponding peptides containing L-Asp. For Gly-Asp-Ala peptides, but not
      Gly-Asp-Hyp, peptides, melting profiles indicated that a mixture of the D- and L
      Asp containing peptides were able to form heterotrimer triple-helical molecules.
      These studies illustrate the dramatic destabilizing effect of D-amino acids on
      the triple-helix stability, but indicate that they can be accommodated in this
      conformation.

PMID- 10079769
TI  - Model peptide studies of sequence repeats derived from the intracrystalline
      biomineralization protein, SM50. I. GVGGR and GMGGQ repeats.
AB  - We report solution-state pulsed field gradient nmr studies of a native sequence
      derived 23-residue peptidomimetic, N alpha-acetyl-QPGVGGRQPGMGGQPGVGGRQPG-C alpha
      amid, that incorporates the prevalent GVGGR and GMGGQ repeats found in the sea
      urchin embryo intracrystalline spicule matrix protein, SM50 (Strongylocentrotus
      purpuratus). These repeats are sequence homologues of elastin protein repeats
      (VPGVG, VGGVG, and APGVGV) and spider dragline silk protein repeats (GPGG, GQGG,
      and QPGYG). Using rotating frame nuclear Overhauser effect (ROE) connectivities,
      CH alpha proton conformational shifts, 3JNH-CH alpha coupling constants, amide
      temperature shift coefficients, and pulsed field gradient ROE spectroscopy
      solvent exchange measurements, we find that the 23-mer peptidomimetic possesses a
      multiple beta-turn structure in aqueous solution, in equilibria with an extended
      or coil structure (60% beta-turn: 40% random coil). The GVGGR sequence adopts a
      double beta-turn conformation that is stabilized by two hydrogen bonds (R7-->V4,
      R20-->V17; G6-->G3, G19-->G16). The GMGGQ region adopts a single beta-turn
      conformation that is stabilized by a hydrogen bond involving residues Q14 and
      M11. Repeating beta-turn structures, or beta-spirals, may play an important role
      with regard to matrix assembly, protein stability, molecular elasticity, and/or
      protein-crystal recognition within the spicule mineralized matrix.

PMID- 10079770
TI  - The role of DNA-protein salt bridges in molecular recognition: a model study.
AB  - A theoretical study is presented of the influence of salt bridges between
      cationic side chains and DNA phosphates on DNA conformation and flexibility. The
      DNA sequence studied is that of the catabolite activator protein binding oligomer
      from the crystallized complex. The effect of salt bridges is modeled by
      neutralization of net phosphate charges for the groups involved in such
      interactions in the crystallized complex. Energy-optimized conformations are
      obtained by molecular mechanics using the JUMNA program. Base sequence dependence
      is studied by moving the phosphate neutralization pattern along the sequence and
      also by point mutations. Normal mode analysis is used to evaluate DNA
      flexibility. The results obtained show that the free oligomer is already
      precurved in the direction favored by the protein, and the effect of phosphate
      neutralization is principally to increase this curvature. This effect is,
      however, strongly sequence dependent. In addition, it is shown that oligomer
      flexibility cannot be explained by a simple superposition of the properties of
      successive dinucleotide steps, strong long-range coupling effects are observed.
      In all the cases examined, phosphate neutralization, however, leads to a
      reduction in oligomer flexibility.

PMID- 10079771
TI  - Identification of unusual amino acids in peptides using automated sequential
      Edman degradation coupled to direct detection by electrospray-ionization mass
      spectrometry.
AB  - The determination of the primary structure of peptides and proteins is routine in
      many laboratories; however, many of the obtained sequences are incomplete or can
      be misinterpreted when the samples contain unusual amino acids. Here we report
      the development of an automated peptide sequenator coupled to an electrospray
      ionization (ESI) mass spectrometer (MS) that, in conjunction with minor
      modifications to the sequencing conditions and, in some cases, prior
      derivatization of amino acids, allows the detection of the phenylthiohydantoin
      (PTH) derivatives of a number of unusual amino acids. Using the coupled
      sequenator-ESI-MS system we were able to determine the complete sequence of the
      lantibiotic gallidermin, a partial sequence of the calcium-dependent peptide
      antibiotic CDA2 as well as the pool sequence of a mixture of synthetic peptides
      containing nonproteinogenic amino acids. In addition to the 20 proteinogenic
      amino acids, the procedure was able to detect PTH derivatives of
      hydroxyphenylglycine, 2,3-didehydroasparagine, 3-methylglutamic acid,
      oxytryptophan, ornithine, N-methylglycine, dihydroxyphenylalanine, and alpha
      aminoisobutyric acid. Similarly, after a simple derivatization procedure, we were
      also able to correctly identify educts of 2,3-didehydroalanine, 2,3
      didehydrobutyrine, lanthionine, and 3-methyllanthionine.

PMID- 10079772
TI  - Access to cardiac resources in Canada: who is responsible? Who is liable?

PMID- 10079773
TI  - What have we done for you lately?

PMID- 10079774
TI  - Digital dreaming.

PMID- 10079775
TI  - Adenosine-induced atrial pro-arrhythmia in children.
AB  - Adenosine has become the preferred acute treatment for common types of
      supraventricular tachycardia because of its efficacy and safety. There have been
      a few reports of serious proarrhythmic events associated with its use, including
      the induction of atrial fibrillation in adult patients. Three instances of
      adenosine-induced atrial proarrhythmia (two atrial fibrillation and one atrial
      flutter) have been observed in children with manifest or concealed Wolff
      Parkinson-White syndrome at the Hospital for Sick Children, Toronto, Ontario
      since 1990, which indicates a previously unreported risk of atrial arrhythmia for
      children as well. Because adenosine may enhance antegrade bypass tract
      conduction, its use carries a risk of ventricular acceleration, including
      progression to ventricular fibrillation. Because of such rare and potentially
      life-threatening adverse effects, appropriate monitoring and precautions are
      required during the administration of the drug to children and adults.

PMID- 10079776
TI  - Potential cost effectiveness of tissue plasminogen activator among patients
      previously treated with streptokinase.
AB  - BACKGROUND: A major limitation of streptokinase is the development and
      persistence of problematic neutralizing antibodies that have the potential to
      limit the effectiveness of repeat streptokinase therapy. Accordingly, tissue-type
      plasminogen activator (t-PA) is frequently administered to patients with
      recurrent infarction presenting more than four days from previous treatment with
      streptokinase. OBJECTIVE: To explore the marginal cost effectiveness of the use
      of t-PA among patients with resistance to streptokinase. MATERIALS AND METHODS: A
      model was developed incorporating short term (five- to six-week) costs and
      mortality data for various thrombolytic strategies. It was assumed that
      streptokinase would be clinically ineffective when administered to streptokinase
      resistant patients. Sensitivity analyses were performed varying the baseline
      mortality, the proportion of patients resistant to streptokinase and the absolute
      survival benefit of t-PA compared with streptokinase. RESULTS: In the absence of
      streptokinase resistance, streptokinase is a cost effective strategy for patients
      with suspected myocardial infarction, even when the expected mortality is low. In
      the presence of streptokinase resistance, the combination of streptokinase and
      acetylsalicylic acid is most cost effective when rates of resistance are low
      ($16,389 per short run survivor with 5% resistance versus $21,306 with 50%
      resistance). t-PA is a cost effective alternative when rates of resistance are
      high ($54,158 per short run survivor with 50% resistance) assuming a 1% absolute
      risk reduction in mortality. As the level of resistance decreases, however, t-PA
      becomes a less cost effective choice ($203,092 per short run survivor with 5%
      resistance). However, t-PA is always more cost effective in the presence of any
      streptokinase resistance than when it is administered for an index myocardial
      infarction. CONCLUSIONS: This analysis shows that using t-PA in patients
      previously treated with streptokinase is a cost effective strategy. t-PA becomes
      less cost effective as the percentage of patients with streptokinase resistance
      decreases, particularly when the absolute risk reduction favouring t-PA over
      streptokinase is small. Nevertheless, if the early mortality advantage is
      sustained, very favourable cost effectiveness ratios are attained with t-PA even
      when the risk of resistance is low. t-PA used in the presence of streptokinase
      resistance is always more cost effective than when it is used for a first
      myocardial infarction.

PMID- 10079777
TI  - Influence of age on ambulatory electrocardiogram-derived heart rate variability.
AB  - OBJECTIVE: To evaluate the quantitative change in heart rate variability with age
      by using 24 h Holter ambulatory monitoring of electrocardiogram and to set the
      lower limit of heart rate variability depending on age. PARTICIPANTS: Eighty
      healthy subjects without any medication (male to female ratio 40:40, 45.6 +/-
      14.1 years of age, range 16 to 68 years). METHODS: Holter monitoring was
      performed, and frequency and time domain heart rate variability was obtained.
      RESULTS: A significant inverse relationship was found between age and heart rate
      variability, especially in the frequency domain, and, in the time domain
      analysis, in the root mean square of the difference in the RR intervals of sinus
      rhythm (NN) between successive beats and in the portion of NN cycles greater than
      50 ms apart. Except for the standard deviation of the mean of RR intervals taken
      every 5 mins and averaged over 24 h and the ratio of low frequency high frequency
      power spectra, all parameters decreased to a certain age and did not change
      thereafter, and the rate of decrease differed among the parameters of heart rate
      variability. Because age had a strong influence on heart rate variability, the
      lower limit of heart rate variability for a certain age was determined by using
      the polynomial curve fitting of the moving average minus 2 SD of 10 consecutive
      subjects. By using these equations, it could be determined whether heart rate
      variability was normal or abnormal depending on age.

PMID- 10079778
TI  - Antiplatelet and lipid-lowering therapies for the secondary prevention of
      cardiovascular disease: are we doing enough?
AB  - OBJECTIVE: To evaluate whether current recommendations with respect to the
      treatment of dyslipidemias and the use of antiplatelet agents are being applied
      in the secondary prevention of cardiovascular disease in primary care settings.
      DESIGN: Descriptive study based on data from the FAMUS (FAmily Medicine,
      Universite de Sherbrooke) primary care register. SETTING AND PARTICIPANTS: Two
      hundred and thirty-three physicians participating in the FAMUS project
      contributed information from nonpregnant patients over 20 years of age consulting
      for a periodic health examination between 1992 and 1996. INTERVENTIONS: Data from
      patients in secondary prevention (those with or having had angina, a previous
      myocardial infarction, bypass surgery, coronary angioplasty or peripheral
      vascular disease) were extracted and analyzed. MAIN RESULTS: Of the 52,505
      patients in the register, 4315 (8%) were identified as being in secondary
      prevention. Overall, 53% were noted as receiving an antiplatelet agent while 4%
      were taking warfarin therapy. Only 64% (2780) had a complete lipid profile on
      record while 38% were being treated with a hypolipidemic agent. In the treated
      group, only 30% had a low density lipoprotein cholesterol level below 3.0 mmol/L
      compared with 22% in the untreated group. CONCLUSIONS: A large number of patients
      identified as being in secondary prevention were not screened for dyslipidemias,
      and, of those who were, the majority were undertreated according to current
      recommendations. Antiplatelet agents were more widely prescribed but potentially
      underused.

PMID- 10079779
TI  - Dofetilide enhances shock-induced extension of refractoriness and lowers
      defibrillation threshold.
AB  - OBJECTIVE: To explore the hypothesis that class III antiarrhythmics reduce
      defibrillation threshold (DFT) by prolonging postshock refractoriness. ANIMALS
      AND METHODS: The effect of a new selective potassium channel blocker, dofetilide
      (DOFlow 2.5 micrograms/kg bolus plus 0.9 microgram/kg/h; DOFmed 10 micrograms/kg
      bolus plus 3.6 micrograms/kg/h; and DOFhigh 25 micrograms/kg bolus plus 9
      micrograms/kg/h), on DFT was compared with that of placebo in anesthetized open
      chest dogs (n = 6 per group). The effects of dofetilide on refractory period
      extension (RPE) were assessed by using DFT strength shocks delivered at various
      stages of repolarization. RESULTS: DFT was significantly decreased in the DOFhigh
      group, whether expressed as shock peak voltage or energy (P < 0.05 compared with
      changes in placebo). At baseline, a shock timing of ventricular effective
      refractory period of 25 ms resulted in RPE of 100 +/- 24 ms, 80 +/- 11 ms, 91 +/-
      14 ms and 90 +/- 20 ms in the placebo, DOFlow, DOFmed, and DOFhigh groups,
      respectively. After infusion, these RPE values were unchanged in the placebo
      group but tended to increase in the dofetilide treatment groups. DOFhigh
      significantly increased RPE by 20 +/- 18 ms (P < 0.05 compared with baseline
      values and changes in placebo). Dofetilide-induced changes in RPE and DFT were
      significantly correlated when expressed as voltage (r2 = 0.78, P < 0.01), current
      (r2 = 0.80, P < 0.01) and energy (r2 = 0.53, P < 0.01). CONCLUSIONS: These
      results show that dofetilide prolonged RPE at a plasma level that reduced DFT,
      thus providing support for the hypothesis that selective prolongation of
      refractoriness may synergize with shock-induced RPE to decrease the energy
      requirements for defibrillation.

PMID- 10079780
TI  - Use of abciximab (c7E3 Fab, ReoPro) as an adjunct to balloon angioplasty.
AB  - OBJECTIVE: To estimate the magnitude of the clinical benefits that may result
      from use of abciximab at the time of angioplasty and the cost of achieving them.
      DATA SOURCES: Four published randomized control trials. DATA SYNTHESIS: Meta
      analysis of outcomes at six months. RESULTS: Use of abciximab in comparable high
      risk populations, in the manner described in these trials, is estimated to have
      the following effects: It does nto influence mortality within the first six
      months. It reduces the rate of myocardial infarction (MI) by 3.3/100 treatments
      with a 95% CI of 1.6 to 5.2. It may reduce the need for revascularization
      (angioplasty or coronary artery bypass graft) by 2.1/100 treatments (95% CI -1.0
      to 5.0). It does not cause any significant increase in major hemorrhagic events.
      There is no evidence that it influences restenosis rates. The net cost per MI
      prevented would be approximately $44,000, ranging from approximately $29,000 to
      $71,000 on sensitivity analysis. The net cost per adverse event prevented (MI
      plus revascularization procedure) would be approximately $27,000 (sensitivity
      analysis $16,000 to $57,000). Use of abciximab for all of the approximately
      17,487 angioplasties carried out in Canada each year may prevent 395 myocardial
      infarcts and 186 revascularization procedures, at an overall cost of
      approximately $29 million and a cost effectiveness of approximately $50,000 per
      adverse event prevented. (This assumes the same proportional reduction in events
      as in these four studies, and that 35% of procedures are high risk).
      SIGNIFICANCE: Possible eventual prolongation of life due to fewer periprocedural
      MIs with abciximab use cannot be quantified. Thus, these estimates of cost
      effectiveness cannot be used to compare this intervention directly with others in
      terms of dollars per life year saved. The field is evolving rapidly and these
      conclusions may soon have to be modified. Increasing use of stents will probably
      slightly reduce, but not abolish, the health benefits of abciximab use. These
      estimates are based on only four trials. However, until more trials are completed
      they provide the best available evidence on which to base policy decisions.

PMID- 10079781
TI  - Gaucher's disease with valve calcification: possible role of Gaucher cells, bone
      matrix proteins and integrins.
AB  - Gaucher's disease, an autosomal recessive storage disease, leads to deposition of
      glucocerebrosides in various organs, especially those of the reticuloendothelial
      system. The heart is not thought to be frequently involved and studies of
      patients with cardiac involvement have concentrated on myocardial involvement.
      Despite careful prior investigation Gaucher cells have never been detected in the
      valves of these patients. Pathological findings of a patient with Gaucher's
      disease, type IIIc, with prominent cardiac valvular involvement are reported and,
      for the first time, the presence of Gaucher cells in the valve tissue is
      documented. There is evidence that the pathogenesis of the valvular injury may be
      by way of a cell-mediated mechanism involving bone matrix proteins and integrins.

PMID- 10079782
TI  - Mycotic aneurysm complicating staphylococcal endocarditis.
AB  - OBJECTIVE: To emphasize the role of noninvasive diagnostic investigative methods
      and their importance in early detection of mycotic aneurysm related to
      staphylococcal endocarditis, and of monitoring therapy or identifying
      complications. PATIENTS AND METHODS: Two patients with mycotic aneurysm that
      developed as complications of staphylococcal endocarditis are presented. The
      first patient had mesenteric artery mycotic aneurysm and presented with sudden
      rupture one month after initial diagnosis of mitral valve infective endocarditis
      and completion of a full course of antimicrobial therapy. The second patient had
      multiple cerebral mycotic microaneurysms and presented with hemorrhagic cerebral
      embolization from aortic valve infective endocarditis. RESULTS: The first patient
      died because of ischemic cerebral edema 48 h after rupture of the mesenteric
      artery mycotic aneurysm and massive hemoperitoneum, which was treated surgically
      with distal ileal resection and ileostomy. The second patient was alive two years
      after prolonged antimicrobial therapy and aortic replacement to treat moderate
      aortic regurgitation and progressive left ventricular enlargement. CONCLUSIONS:
      Mycotic aneurysm is a rare complication of infective endocarditis but has a high
      mortality rate because of its early or late potential catastrophic rupture.
      Diagnosis by noninvasive diagnostic imaging techniques of mycotic aneurysm before
      rupture would be beneficial for its treatment.

PMID- 10079783
TI  - Post-traumatic thoracic pseudoaneurysm repair with an endoluminal expandable
      stent.
AB  - Recent technological improvement has allowed endoluminal correction of thoracic
      and abdominal aortic aneurysm through percutaneous insertion of expandable
      stents. A woman who presented with chronic pseudoaneurysm of the thoracic aorta
      10 years after being in a car accident is presented. A Talent stent was
      introduced through the femoral artery and successfully deployed under
      fluoroscopic guidance across the aneurysmal defect. Recovery was uneventful, and
      12 months later the patient remained asymptomatic.

PMID- 10079784
TI  - One-stage repair of a massive aortic arch aneurysm.
AB  - A 61-year-old woman with a massive aortic aneurysm extending from the aortic root
      to the proximal descending thoracic aorta required urgent surgical intervention.
      She underwent successful replacement of her ascending aorta, transverse arch and
      descending aorta in a single operation.

PMID- 10079785
TI  - Erectile dysfunction in the cardiovascular patient.

PMID- 10079786
TI  - The case for early identification of hearing loss in children. Auditory system
      development, experimental auditory deprivation, and development of speech
      perception and hearing.
AB  - Human infants spend the first year of life learning about their environment
      through experience. Although it is not visible to observers, infants with hearing
      are learning to process speech and understand language and are quite
      linguistically sophisticated by 1 year of age. At this same time, the neurons in
      the auditory brain stem are maturing, and billions of major neural connections
      are being formed. During this time, the auditory brain stem and thalamus are just
      beginning to connect to the auditory cortex. When sensory input to the auditory
      nervous system is interrupted, especially during early development, the
      morphology and functional properties of neurons in the central auditory system
      can break down. In some instances, these deleterious effects of lack of sound
      input can be ameliorated by reintroduction of stimulation, but critical periods
      may exist for intervention. Hearing loss in newborn infants can go undetected
      until as late as 2 years of age without specialized testing. When hearing loss is
      detected in the newborn period, infants can benefit from amplification (hearing
      aids) and intervention to facilitate speech and language development. All
      evidence regarding neural development supports such early intervention for
      maximum development of communication ability and hearing in infants.

PMID- 10079787
TI  - The role of the pediatrician in hearing loss. From detection to connection.
AB  - The advocacy by pediatricians is imperative if early hearing detection and
      intervention (EHDI) programs are to be effective, efficient, and successful over
      the long term. Some pediatricians remain unfamiliar with the rationale for
      universal screening of all newborns prior to hospital discharge. Pediatricians'
      questions regarding universal screening are data- and quality-driven. Discussion
      of the components of the EHDI program, answers to pediatricians' most frequently
      asked questions, supported by data, and the quality indicators used to monitor
      EHDI programs in Texas are provided.

PMID- 10079788
TI  - A stepwise approach to the diagnosis and treatment of hereditary hearing loss.
AB  - What To Do Do suspect a genetic cause in all cases of hearing loss. Do develop a
      working knowledge of common types of HHI that you may draw on to aid in
      diagnosis. Do think of HHI when the audiogram reveals a hearing loss with a
      "cookie bite" configuration. Do refer the infant to a geneticist in cases where
      you suspect a syndromic HHI, a nonsyndromic HHI, and in cases of "cryptogenic"
      hearing loss where an underlying HHI may be present. Often, the associated
      symptoms are subtle and best detected by a professional who deals with these
      issues on a daily basis. Do get the infant or family plugged into an audiologist
      or otolaryngologist and speech pathologist who will preferably work as a team to
      maximize aural rehabilitation and ensure serial follow-up. It is never too early
      to fit a child with hearing aids. Do refer to the HHIRR center at Boys Town. Do
      refer to the correct "deaf" organization or "blind-deaf" organization. Do think
      about working up other siblings or family members. Do keep in mind that some
      members of the "deaf society" may regard deafness as an alternative lifestyle and
      may not be amenable to their child's referral for additional workup and aural
      rehabilitation. What Not To Do Do not assume the child is deaf and nothing can be
      done. Do not wait until the child is older to refer to an otolaryngologist,
      speech therapist, and audiologist. Do not order a sonogram. Do not order a
      temporal bone CT scan on newborns. Do not forget about other siblings who may
      have a similar pathology. Do not forget that some forms of HHI can present beyond
      infancy. The pediatrician is the front line and can play a major role in the
      diagnosis, workup, and treatment of HHI. Armed with the proper degree of
      suspicion, careful elicitation of family history, meticulous physical
      examination, evaluation of the audiogram, and adequate fund of knowledge of
      common types of genetic deafness, the pediatrician can make a timely diagnosis
      and appropriate referrals. This avoids delay in detection of significant hearing
      impairment and the associated lack of essential skills in speech, language, and
      social interaction. No child is too young to have some type of hearing
      assessment. Early detection and intervention are best done with a
      multidisciplinary team approach with a neonatologist or pediatrician,
      audiologist, speech therapist, and otolaryngologist. In the future, blood tests
      using genetic probes may be available to screen for many types of HHI.

PMID- 10079789
TI  - Etiology of hearing loss in children. Nongenetic causes.
AB  - Every child with a hearing loss should have an evaluation to determine the cause
      of hearing loss. This article focuses on the nongenetic origins of hearing loss,
      the most frequent of which is the neonatal intensive care unit experience,
      followed by meningitis, cytomegalovirus, and other infections. Preventable causes
      such as exposure to ototoxic medications and noise are also discussed in this
      article.

PMID- 10079790
TI  - Minimal, progressive, and fluctuating hearing losses in children.
      Characteristics, identification, and management.
AB  - Referring to specific types of hearing loss as "minimal" or "mild" seems to imply
      that their effects are equally mild or negligible. A growing body of literature,
      however, supports the notion that such losses can have a significant impact on
      the communicative and educational development of young children. Although OME is
      considered a common childhood ailment, mounting evidence suggests that it is not
      always benign and may contribute to significant educational and communicative
      difficulties in some young children when accompanied by conductive hearing loss.
      Even very mild bilateral and unilateral SNHL seems to contribute to problems in
      the areas of social and emotional function, educational achievement, and
      communication in some children. Because these hearing losses are so mild, they
      may not be immediately recognized as the source of such difficulties. The purpose
      of this report is to heighten the general pediatrician's awareness of the
      significance of even very mild or minimal hearing losses in children. As the
      gatekeepers for children's health care, pediatricians are typically the primary
      recipients of parental expressions of concern and the initiators of evaluations
      or referrals to address such.

PMID- 10079791
TI  - The efficacy of early identification and intervention for children with hearing
      impairment.
AB  - From these findings, the inevitable conclusion is that identification of hearing
      loss by 6 months of age, followed by appropriate intervention, is the most
      effective strategy for the normal development of language in infants and toddlers
      with hearing loss. Identification of hearing loss by 6 months can only be
      accomplished through universal newborn hearing screening. Some questions that
      arise as a result of these studies include: What can one conclude from the
      finding that the language skills of children with mild hearing losses are no
      better than those with greater losses? If the finding holds up, it indicates a
      great need for investigations into biobehavior theories of language acquisition
      and into the part played by the prenatal 4 months of hearing. And it also shows a
      need for answering the question, When does a hearing loss begin?, because it
      certainly seems that all hearing losses are similar in their outcomes. Can the
      findings from these studies be used to benefit normally hearing children who are
      at risk for language delays as a result of limited language environments? Such
      children suffer from auditory deprivation just as surely as those with hearing
      losses. If the language skills of the latter children can be brought to normal
      range by early intervention, the same strategy may help high-risk populations.
      The efficacy of early intervention is just as valid for these children as it is
      for the children with hearing impairment. Now that the benefits of early
      identification of children with congenital hearing loss have been demonstrated,
      these benefits should be extended to all children who are at risk for language
      delays, with appropriate interventions applied immediately.

PMID- 10079792
TI  - State programs for universal newborn hearing screening.
AB  - Published reports of several statewide and hospital-based systems for universal
      newborn hearing screening demonstrate that successful large-scale programs that
      appropriately identify infants with hearing loss in the earliest months of life
      can be developed. These programs are characterized by nursery-based screening
      rates of 95% or higher, referral rates of 6% or less, and reasonable per-infant
      costs. Less data are available regarding the outcome of these screening programs
      in ensuring confirmation of hearing loss by 3 months of age and initiation of
      intervention by 6 months of age. The results of the MDNC survey provide important
      information on the status of newborn hearing screening, audiologic assessment,
      and intervention services in 16 states. The survey reveals that hospitals have
      initiated universal newborn hearing screening programs using appropriate
      technology but that confirmation of hearing loss, fitting of amplification, and
      enrollment in early intervention are often delayed beyond the JCIH
      recommendations. Several factors might contribute to late confirmation of hearing
      loss and delayed amplification and intervention. First, as shown in the Colorado
      report, lack of a mandatory statewide system for tracking and reporting may delay
      transition of infants and families from screening to diagnosis, and diagnosis to
      intervention. In addition, many states lack a centralized system for reporting
      confirmed hearing loss. Successful statewide programs for universal newborn
      hearing screening, audiologic diagnosis, and early intervention depend on data
      reporting strategies that facilitate transition of infants and families through a
      system of care. Second, lack of understanding about the urgent need for
      intervention in the earliest months of life may hinder referral to early
      intervention programs. Recent data from Colorado's universal newborn hearing
      screening program reveals that infants who are deaf or who have hearing losses
      achieve significantly better language development outcomes if intervention begins
      before age 6 months than infants whose intervention begins after 6 months of age.
      Hopefully, as these data become more widely available, the compelling need for
      early intervention will facilitate transition into these services. Although
      universal newborn hearing screening programs are increasing rapidly, states have
      not yet developed the coordinated systems for linking universal newborn hearing
      screening programs to audiologic diagnostic services and audiologic diagnostic
      services to early intervention programs. Key issues impeding development of these
      systems may be lack of tracking and reporting systems, lack of standardized
      guidelines for screening, diagnostic audiologic assessment, hearing aid fitting
      for very young infants, and lack of understanding about the compelling need for
      intervention in the earliest months of life. Development of complete systems of
      care must become a priority for universal newborn hearing screening to provide
      its ultimate benefit.

PMID- 10079793
TI  - Factors influencing the efficacy of universal newborn hearing screening.
AB  - The debate surrounding the issue of universal hearing screening is being carried
      out on several levels. Although little disagreement exists over the educational,
      vocational, and quality-of-life benefits that would result from early
      identification and timely intervention of congenital hearing loss, the pragmatic
      issues, such as the effectiveness and the cost benefits associated with universal
      screening, cannot be ignored. This means that sensitivity, specificity,
      prevalence, and predictive value remain important factors. Determining the number
      of infants born with hearing loss in the United States each year, the prevalence
      issue is key to calculating the predictive value of newborn hearing screening.
      Emerging from current studies is that estimates of prevalence in the universal
      newborn population vary from 0.9 in 1000 for permanent bilateral hearing loss of
      more than 35 dB, to 3.24 in 1000 for bilateral hearing loss, to 5.95 in 1000 when
      unilateral and moderate hearing loss infants are counted. By comparison, the
      incidence of hearing loss in the NICU or at-risk population is accepted as high,
      somewhere between 2% and 4% or 20 to 40 in 1000. Incidence in the NICU varies
      depending on admission policies and level of care. In general, however, by
      screening the NICU and targeted at-risk populations, estimated to make up 10% to
      16% of the newborn population, half or more of all newborns with severe to
      profound educationally disabling hearing loss are identified. Data from several
      well-conducted clinical studies, dating back to the first studies on the use of
      ABR to screen in the NICU, provide ample justification for the recommendation
      that all infants admitted to an NICU for longer than 24 hours should be screened
      for hearing impairment regardless of whether they have any of the at-risk
      indicators for hearing loss. In the author's opinion, screening in the NICU
      should be modeled on the operator-controlled ABR protocol outlined by Galambos
      and colleagues, with the addition that every ABR fail be screened by OAE before
      discharge. Unlike the targeted NICU population, the question remains for well
      infants, is sufficient clinical data or evidence available to justify screening
      all well newborns, specifically those with none of the at-risk for hearing loss
      indicators cared for in the well-infant nursery and who are discharged home
      within 24 or 48 hours? With the steady increase in the number of hospital-based
      universal newborn hearing screening programs implemented since the NIH Consensus
      Statement, additional data should become available to help resolve several
      outstanding issues, including prevalence and the predictive value of the various
      test protocols currently in use or proposed.

PMID- 10079794
TI  - Physiologic and behavioral approaches to pediatric hearing assessment.
AB  - A behavioral approach is the first choice for hearing assessment in infants and
      children. It is the only true test of hearing. Physiologic measures are not tests
      of hearing, only indicators of auditory function. The use of physiologic measures
      in estimating hearing levels makes some presumptions regarding the concept of
      hearing. As such, these measures are used when a definitive statement about
      hearing cannot be made on the basis of behavioral audiometric results, or when
      other factors (e.g., age or developmental delay) preclude obtaining reliable
      behavioral information.

PMID- 10079795
TI  - Management of the child with sensorineural hearing loss. Medical, surgical,
      hearing aids, cochlear implants.
AB  - Optimal comprehensive management of a child with SNHL involves constructive
      dialogue and coordination with the child's family and teachers. Not all children
      with SNHL benefit from conventional amplification, even after parents have
      invested significant amounts of money in hearing aids. Parents may encounter
      frustration and disappointment if their children fail to achieve communicative
      and academic goals they have established in their own mind. If the child is a
      potential candidate for cochlear implantation, this decision not only involves
      the risks (albeit modest) of surgery but also often a substantial financial
      commitment to help defray the cost of this sophisticated electronic device. The
      parents may encounter conflicting advice from friends and members of the adult
      deaf community about the benefit of cochlear implantation. Throughout the course
      of all of these difficult considerations, the health professionals caring for a
      child with hearing loss should be a source for information, guidance, and support
      to the family.

PMID- 10079796
TI  - Considerations in the education of children with hearing loss.
AB  - It is crucial to the development of speech, language, academic, social, and
      vocational skills that children with a hearing loss be identified as early as
      possible with an intervention plan developed that encourages family inclusion and
      participation. Research indicates that early intervention is key to speech
      intelligibility and the development of age-appropriate language skills. Bess and
      colleagues found that without appropriate intervention, children with minimal
      hearing loss experience significant academic delay and social-emotional problems
      by the third grade. Because most children with an educationally significant
      hearing loss are in the mainstream of regular education, the best hope for true
      integration and inclusion is to implement a proactive management plan that
      prevents failure with its lifelong consequences.

PMID- 10079797
TI  - Organization resources for families of children with deafness or hearing loss.
AB  - National health and education mandates emphasize the value of and need for early
      identification and intervention for children who are deaf and hard of hearing.
      Pediatricians in collaboration with other professionals in a multidisciplinary
      approach play a vital role in linking families to appropriate care. Understanding
      the concept of choices in communication and education resources and the process
      of parental and caregiver grieving enables the pediatrician to assist the family
      in finding needed services, agencies, and resources.

PMID- 10079798
TI  - Therapeutic apheresis in the United States: current indications and directions.

PMID- 10079799
TI  - Overview of therapeutic apheresis in the U.S.A.
AB  - This article provides an overview of therapeutic plasma exchange in the United
      States. The original continuous flow blood cell separator was developed in the
      U.S.A. and remains the most popular type of equipment used. Treatments are
      expensive and limited by insurance reimbursement. Covered diseases are already
      established, with most of the treatments falling into those for hematologic and
      neurologic diseases. The majority of therapeutic plasma exchange is performed for
      a limited number of diagnoses. An estimated 110,000 treatments were provided in
      1997, the majority in hospital-based units. It is unclear whether these numbers
      will increase or decline with the increasing limitations in reimbursement by
      insurance companies.

PMID- 10079800
TI  - Plasmapheresis and paraproteinemia: cryoprotein-induced diseases, monoclonal
      gammopathy, Waldenstrom's macroglobulinemia, hyperviscosity syndrome, multiple
      myeloma, light chain disease, and amyloidosis.
AB  - Therapeutic plasmapheresis has been in widespread use as either a primary or
      adjunctive therapy in the United States since the 1960s. There are several types
      of plasmapheresis procedures used to treat various diseases. Plasma exchange with
      a centrifugal plasma separator using replacement fluid such as human albumin
      solution is the most widely used method in the United States. Other forms of
      plasmapheresis include membrane plasma separation, membrane fractionation,
      cryofiltration apheresis, immunoadsorption, and chemical affinity column
      pheresis. Therapeutic plasmapheresis has been used for the treatment of
      paraproteinemia to remove harmful paraproteins. Paraproteinemia is a disease
      classification in which abnormal or large amounts of plasma proteins such as
      cryoproteins or immunoglobulins are produced. In most cases, plasmapheresis is
      used in combination with corticosteroids and immunosuppressive drugs to prevent
      production of abnormal proteins or to treat the underlying disease. Cryoprotein
      induced diseases, which include cryoglobulinemia, cryofibrinogenemia, and cold
      IgM antibody agglutinin with cryoglobulin properties, are a subclass of
      paraproteinemia. Other categories of paraproteinemia include monoclonal
      gammopathy, Waldenstrom's macroglobulinemia, hyperviscosity syndrome, multiple
      myeloma, light chain disease, and amyloidosis. Some of these diseases may be
      interrelated, and they may be associated with one another. In this review paper,
      we discuss the role of plasmapheresis in the specific classes of paraproteinemia
      in the United States, including our own experience.

PMID- 10079801
TI  - Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances
      in diagnosis, pathophysiology, and management.
AB  - Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP)
      syndrome and improve mortality and relapse rates are hindered by its poorly
      understood pathophysiology. Variability in the application of therapeutic plasma
      exchange (TPE), including replacement fluid strategies, desirable endpoints in
      the platelet count, serum lactate dehydrogenase concentration, and the use of a
      TPE taper, limit comparisons among published studies. The diversity of adjunctive
      therapies such as antiplatelet agents, steroids, and splenectomy further clouds
      comparisons. Recent progress in the diagnosis, pathophysiology, and management of
      TTP syndrome are summarized. The possible role of occult infection and newly
      emerging associations such as ticlopidine therapy are discussed. Advances in
      possible pathogenic mechanisms, the rationale for different replacement fluids
      including the recently licensed solvent-detergent treated plasma, and progress in
      the apheresis management of TTP syndrome are presented.

PMID- 10079802
TI  - Therapeutic apheresis for renal disorders.
AB  - Many primary renal diseases are associated with either antibody deposition within
      the glomerulus or an antibody associated autoimmunity, as may be seen with
      certain vasculitidies. Other immunoglobulins may be nephrotoxic or
      glomerulopathic; such may be the case with myeloma related light chains or
      cryoglobulins. Given the rapid removal of immunoglobulins by therapeutic plasma
      exchange, this modality has been considered an appealing management option in the
      treatment of these autoimmune related renal diseases. Although not classically
      considered as autoimmune diseases, thrombotic thrombocytopenic purpura and
      hemolytic uremic syndrome are related syndromes which often involve the kidneys.
      In many cases therapeutic plasma exchange has been found to be a useful treatment
      modality for these microangiopathic hemolytic anemias. This paper will provide a
      concise review of the renal indications for therapeutic plasma exchange.

PMID- 10079803
TI  - Critical care apheresis: hepatic failure.
AB  - Hepatic failure is a common feature of critical care. Most hepatic dysfunction in
      the ICU responds to medical management and metabolic support. The role of
      extracorporeal organ support in hepatic failure is not as well defined as it is
      in renal failure and pulmonary failure. Nevertheless, artificial organ support
      has been successful in the treatment of advanced liver failure. Hybrid
      bioartificial liver substitutes show great promise, especially as a bridge to
      liver transplant.

PMID- 10079804
TI  - Apheresis in thoracic organ transplantation.
AB  - The beneficial addition of cyclosporine and tacrolimus to the immunosuppressive
      armamentarium have unfortunately only partially solved the problems of acute and
      chronic rejection in thoracic organ transplantation. Apheresis techniques offer
      creative avenues for modifications of allograft rejection. Plasmapheresis can be
      used for mechanical reduction of alloantibody burdens in highly sensitized
      patients and permit transplantation in an otherwise almost hopeless situation and
      can also be used on a short-term basis for the treatment of acute humoral
      rejection. Extracorporeal photochemotherapy holds promise as a possibly
      synergistic adjunct to conventional therapy and may even reduce the severity of
      graft vasculopathy. The increasing availability of highly specific column
      immunoadsorption techniques may further increase the applicability of apheresis
      in transplantation.

PMID- 10079805
TI  - The role of therapeutic apheresis in the treatment of cancer: a review.
AB  - Immunosuppression is a hallmark of advanced malignancies in man. Over the past 40
      years, many investigators have identified soluble immunosuppressive factors in
      blood, serum, ascitic fluid, and pleural fluid from cancers in man and other
      species. Suppressive factors have also been identified that are produced by
      tumors. The description of immunosuppressive factors in the blood of vertebrates
      who either have cancer or who are pregnant is significant, for only in pregnancy
      and cancer does a seemingly normal immune system tolerate immunogenic neoantigen.
      Tumor necrosis factors (TNFs) are known to be pleiotropic cytotoxic cytokines
      that are produced by macrophages and lymphocytes. These cells are thought to be
      suppressed in patients who have cancer or who are pregnant. Recently, elevated
      blood levels of soluble tumor necrosis factor receptors (sTNFRs) have been
      reported in the blood in a variety of cancers and pregnancy. In 1990, after our
      initial publication of the discovery of sTNFRs in the serum and low molecular
      weight ultrafiltrates of serum from a variety of cancer patients, others
      confirmed significant elevations of sTNFRs in cancer patients. This elevation was
      found to correlate with a poor prognosis. The biologic activity of
      proinflammatory cytokines as well as the suppressive role of their shed receptors
      is herein reviewed. Work with cancer patients using ultrapheresis to reduce these
      suppressive molecules by the authors and others is reviewed. Several
      recommendations are made for future directions.

PMID- 10079806
TI  - The North American experience with photopheresis.
AB  - Photopheresis or extracorporeal photochemotherapy (ECP) is a novel
      immunomodulatory therapy based upon pheresis of light-sensitive cells. Whole
      blood is removed from patients who have previously ingested the photosensitizing
      agent 8-methoxypsoralen (8-MOP) followed by leukapheresis and exposure of the 8
      MOP containing white blood cells (WBCs) extracorporeally to an ultraviolet A
      (UVA) light source prior to their return to the patient. In 1988, the Food and
      Drug Administration (FDA) approved photopheresis for the treatment of cutaneous T
      cell lymphoma (CTCL). Treatment of CTCL with photopheresis has been reported in
      over 300 patients worldwide. Photopheresis has also demonstrated encouraging
      results in the treatment of solid organ transplant rejection, graft versus host
      disease, scleroderma, and other autoimmune diseases although fewer patients have
      been studied. This review will focus on the North American experience with
      photopheresis.

PMID- 10079807
TI  - Preliminary evaluation study of a prototype hollow fiber membrane for the
      continuous membrane autotransfusion system.
AB  - A totally new autotransfusion system has been developed utilizing a hollow fiber
      membrane, based upon plasmapheresis technology. Prior to fabricating the system,
      it was essential to evaluate the basic performance characteristics of the filter,
      which was designed particularly for the new system. The objective of this study
      was to prove or disprove that such a system would be available using this filter.
      An in vitro study was conducted on the filter using bovine blood. The result of
      the study showed that the filter could process 2-20% of hematocrit blood at a
      flow rate greater than 250 ml/min of inlet blood continuously. Moreover, it could
      concentrate 5-20% hematocrit blood to hematocrit percentages greater than 40% by
      a single passage through the filter. These results seemed to prove that a rapid,
      continuous, and compact autotransfusion system could be developed using this
      filter.

PMID- 10079808
TI  - Miller Fisher syndrome with central involvement: successful treatment with
      plasmapheresis.
AB  - Miller Fisher syndrome is characterized by external ophthalmoplegia, ataxia, and
      areflexia. Most researchers favor a peripheral origin while others suggest a
      brainstem inflammatory lesion or a combination of central and peripheral
      demyelination. We report 2 cases of Miller Fisher syndrome with the typical triad
      of ataxia, areflexia, and ophthalmoplegia. Strong clinical evidence of central
      involvement included initial drowsiness, bilateral Babinski sign, and
      quadriparesis. Evoked potential studies showed prolongation of central conduction
      time. Plasmapheresis was performed to relieve respiratory failure in Patient 1
      and to shorten the duration of nasogastric tube feeding due to severe bulbar
      palsy in Patient 2. Significant improvement of electrophysiologic parameters was
      recorded after plasmapheresis. Abnormal evoked potentials, together with clinical
      evidence of central nervous system abnormalities, support the hypothesis that
      there is a combination of peripheral and central involvement in Miller Fisher
      syndrome in our patients. Plasmapheresis is highly effective in relieving the
      profound neurological deficits of this atypical syndrome.

PMID- 10079809
TI  - Treatment with steroids and double filtration plasmapheresis for a case of anti
      GQ1b antibody-positive Bickerstaff's encephalitis.
AB  - The treatment of Bickerstaff's brainstem encephalitis (BBE) is still
      controversial. We report a case of BBE with positive anti-GQ1b antibody. The
      patient was successfully treated with steroids and double filtration
      plasmapheresis.

PMID- 10079810
TI  - Evaluation of adsorption selectivity dextran sulfate bound cellulose beads for
      the removal of anti-DNA antibodies.
AB  - The purpose of this study was to clarify the basic adsorption selectivity
      characteristics of dextran sulfate (DS) columns (Selesorb, Kaneka Corporation,
      Osaka, Japan). Recovery rates of blood chemical components, hormones, coagulation
      factors, and antinuclear antibodies (anti-SS-A, SS-B, Sm, Scl-70, and RNP
      antibody) in vitro were assessed by mixing normal volunteers' or patients' sera
      with DS bound cellulose beads. For tested blood chemical components other than
      triglyceride and total cholesterol, the recovery rate was not changed
      significantly by incubation. No significant changes in hormone levels resulted
      from incubation. Among coagulation factors, the activities of antithrombin III,
      plasminogen, and factors V, VIII, IX, XI, and XII were significantly reduced by
      incubation. Among antinuclear antibodies tested, anti-SS-A and anti-RNP were
      absorbed to some extent, but not anti-SS-B, Sm, or Scl-70 antibodies. Taking into
      account these characteristics, apheresis therapy using a DS column should be
      performed.

PMID- 10079811
TI  - Copper transport in mammals.

PMID- 10079812
TI  - Models to evaluate health risks derived from copper exposure/intake in humans.

PMID- 10079813
TI  - Cu metabolism in the liver.
AB  - This paper has, given some idea of our concepts of the processes involved in the
      transport of Cu across cell membranes in the liver, which we have summarised in
      Fig 1. Cu(II)His2 is reduced to Cu(I). This is transported across the membrane,
      re-oxidised, either before or after binding to glutathione (Freedman et al.,
      1989) or HAH1 (Klomp et al., 1997), binds to SAHH, and donates Cu(II) to the
      ATPase. It is very interesting that cells which are very diverse from an
      evolutionary point of view still use very similar methods to handle the metal.
      Whether regulation of transport is also the sam remains to be seen. We would
      guess that, although there will be strong similarities, there will also be very
      significant differences, reflecting the different environments seen by different
      tissues in mammalian cells and given the different requirements of the tissues.

PMID- 10079814
TI  - Multiple forms of the Menkes Cu-ATPase.
AB  - The 5' region of MNK cDNAs has a 45 bp insert terminating at the 5'end with an
      AGATG sequence. The ATG in the sequence is in-frame with the ATG downstream
      identified by Vulpe et al (1993) as a translation start site for MNK mRNA.
      Inserts of 192 bp and 45 bp have been found in the 5' region of MNK mRNAs from
      BeWo cells, Caco-2 cells and normal human fibroblasts. Extensions to the 5' end
      of these mRNAs could foretell a modified N-termini in certain forms of the Menkes
      Cu-ATPase. These modified H2N-terminal extensions are postulated to be targeting
      signals for post-translational processing and cellular localization. In this
      report, we provide evidence that the primary Menkes transcript in non-Menkes
      cells undergoes post-transcriptional splicing that gives rise to multiple
      transcripts. The data suggest that the Menkes gene is a copper locus that codes
      for more than one form of the Menkes Cu-ATPase and one of these forms could be a
      small Cu transport protein.

PMID- 10079815
TI  - The cell biology of the Menkes disease protein.

PMID- 10079816
TI  - Functional analysis of the Menkes protein (MNK) expressed from a cDNA construct.

PMID- 10079817
TI  - Mutation spectrum of ATP7A, the gene defective in Menkes disease.
AB  - Our knowledge about Menkes disease (MD) has expanded greatly since its
      description in 1962 as a new X-linked recessive neurodegenerative disorder of
      early infancy. Ten years later a defect in copper metabolism was established as
      the underlying biochemical deficiency. In the beginning of 1990s efforts were
      concentrated on the molecular genetic aspects. The disease locus was mapped to
      Xq13.3 and the gene has been isolated by means of positional cloning. This was
      the beginning of a series of new findings which have greatly enhanced our
      understanding of copper metabolism not only in human, but also in other species.
      This review will focus on the molecular genetic aspects of Menkes disease and its
      allelic form occipital horn syndrome. The mutations will be compared briefly with
      those described in the animal model mottled mouse, and in Wilson disease, the
      autosomal recessive disorder of copper metabolism.

PMID- 10079818
TI  - Animal models of Menkes disease.

PMID- 10079819
TI  - Developmental expression of the mouse mottled and toxic milk genes.

PMID- 10079820
TI  - The treatment of Wilson's disease.

PMID- 10079821
TI  - Indian childhood cirrhosis and Tyrolean childhood cirrhosis. Disorders of a
      copper transport gene?

PMID- 10079822
TI  - Animal models of Wilson's disease.

PMID- 10079823
TI  - Copper-binding properties of the N-terminus of the Menkes protein.

PMID- 10079824
TI  - Expression, purification, and metal binding characteristics of the putative
      copper binding domain from the Wilson disease copper transporting ATPase (ATP7B).

PMID- 10079825
TI  - Structure/function relationships in ceruloplasmin.

PMID- 10079826
TI  - Autoxidation of amyloid precursor protein and formation of reactive oxygen
      species.

PMID- 10079827
TI  - Copper-zinc superoxide dismutase and ALS.

PMID- 10079828
TI  - A study of the dual role of copper in superoxide dismutase as antioxidant and pro
      oxidant in cellular models of amyotrophic lateral sclerosis.

PMID- 10079829
TI  - The effect of copper on tight junctional permeability in a human intestinal cell
      line (Caco-2).

PMID- 10079830
TI  - Metal regulation of metallothionein gene transcription in mammals.

PMID- 10079831
TI  - Copper-regulatory domain involved in gene expression.

PMID- 10079832
TI  - Intracellular pathways of copper trafficking in yeast and humans.
AB  - In the bakers yeast S. cerevisiae, there at least four intracellular targets
      requiring copper ions-1) Ccc2p and Fet3p in the secretory pathway (homologues to
      Menkes/Wilson proteins and ceruloplasmin); 2) cytochrome oxidase in the
      mitochondria; 3) copper transcription factors in the nucleus; and 4) Cu/Zn
      superoxide dismutase (SOD1) in the cytosol. We have discovered a small soluble
      copper carrier that specifically delivers copper ions to the secretory pathway.
      This 8.2 kDa factor known as Atx1p, exhibits striking homology to the MERp
      mercury carrier of bacteria and contains a single MTCXXC metal binding site also
      found in the Menkes/Wilson family of copper transporting ATPases. Our studies
      show that Atx1p is cytosolic and facilitates the delivery of copper ions from the
      cell surface copper transporter to Ccc2p and Fet3p in the secretory pathway;
      furthermore, it is not involved in the delivery of copper ions to the
      mitochondria, the nucleus or cytosolic SOD1, implicating specific signals
      directing Atx1p to the secretory pathway. Homologues to Atx1p have been found in
      invertebrates, plants and humans, and the human gene is abundantly expressed in
      all tissues. In addition to Atx1p, we have recently uncovered an additional metal
      trafficking protein that appears to specifically deliver copper ions to SOD1.
      Mutants in the corresponding gene (lys7) are defective for SOD1 activity, and are
      unable to incorporate copper into SOD1, while there is no obvious impairment in
      copper delivery to cytochrome oxidase of Fet3p. The encoded 27 kDa protein
      contains a single MHCXXC consensus copper binding sequence and close homologues
      have been identified in a wide array of eukaryotic species including humans.

PMID- 10079833
TI  - Copper homeostasis in Enterococcus hirae.

PMID- 10079834
TI  - Molecular specificity of synaptic changes responsible for associative memory.

PMID- 10079835
TI  - Behavioral and mechanistic bases of long-term habituation in the crab
      Chasmagnathus.

PMID- 10079836
TI  - Bioactive lipids and gene expression in neuronal plasticity.

PMID- 10079837
TI  - Surface protein phosphorylation by ecto-protein kinases. Role in neuronal
      development and synaptic plasticity.

PMID- 10079838
TI  - Extracellular ATP-induced apoptosis in PC12 cells.
AB  - Studies in our laboratory indicate that extracellular ATP (ATP)o may induce cell
      death by reactive oxygen insults. We have also shown that the Ca(2+)-induced
      oxidative stress as elicited by ATP may lead to an activation of a specific AP-1
      activity. Since early impairment of mitochondria constitutes a critical event of
      the apoptotic cell death, we have examined whether (ATP)o will affect
      mitochondrial damage and cell injury by using mitochondrial specific probes,
      dihydrorhodamine and 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT). We have found that (ATP)o induced cell death in a concentration dependent
      manner by MTT assay. The (ATP)o induced cell death correlated well with the
      reactive oxygen species (ROS) generation in mitochondria, since (ATP)o enhanced
      both cell death and ROS production and antioxidant blocked both of these
      processes. We found (ATP)o treatment led to apoptotic cell death by examining DNA
      laddering and the TUNEL assay. Interestingly, vitamin C and vitamin E combined
      treatment appeared to attenuate the (ATP)o-induced apoptosis. Results indicated
      that (ATP)o may cause oxidative damage of mitochondria leading to apoptotic cell
      death. Antioxidants may be useful in preventing apoptosis by preventing ROS
      formation in mitochondria.

PMID- 10079839
TI  - The role of the neural growth associated protein B-50/GAP-43 in morphogenesis.

PMID- 10079840
TI  - Avian hippocampus as a model to study spatial orientation-related synaptic
      plasticity.

PMID- 10079841
TI  - Metabotropic glutamate receptors in the plasticity of excitatory responses in the
      hippocampus. Clinical impact.

PMID- 10079842
TI  - Familial amyotrophic lateral sclerosis and Alzheimer's disease. Transgenic
      models.

PMID- 10079844
TI  - Influence of phospholipids and sequential kinase activities on tau in vitro.

PMID- 10079843
TI  - Proteins implicated in Alzheimer disease. The role of FE65, a new adapter which
      binds to beta-amyloid precursor protein.

PMID- 10079845
TI  - Cell culture models of neuronal degeneration and neuroprotection. Implications
      for Parkinson's disease.

PMID- 10079846
TI  - Aging and dementia of the Alzheimer type in persons with mental retardation.

PMID- 10079847
TI  - Emerging viral infections.

PMID- 10079848
TI  - Outpatient management of the febrile neutropenic child with cancer.

PMID- 10079849
TI  - Molecular mechanisms of brain damage in bacterial meningitis.

PMID- 10079850
TI  - Dermatophyte infections in children.

PMID- 10079851
TI  - Hepatitis C virus infection.

PMID- 10079852
TI  - Invasive group A streptococcal infections in children.
AB  - Invasive group A streptococcal infections and STSS have increased as causes of
      morbidity and mortality among children and adults. In children, respiratory foci
      appear to be the most common, but skin and soft tissue infection, particularly
      associated with varicella, also are common. Early diagnosis requires awareness of
      the presenting features and a high index of suspicion. Antimicrobial therapy that
      includes clindamycin, therapy with IVIG for those with STSS, and surgical
      intervention for patients with necrotizing fasciitis may improve outcome.
      Chemoprophylaxis should be considered among household contacts of patients with
      severe group A streptococcal disease in high-risk settings. Further studies are
      ongoing to evaluate the hypothesized link of invasive group A streptococcal
      infection in children with varicella and NSAID use, to better clarify the
      pathogenesis of STSS and necrotizing fasciitis, and to better document the risk
      of secondary spread among close contacts of case patients.

PMID- 10079853
TI  - Infectious diseases in internationally adopted children: findings in children
      from China, Russia, and eastern Europe.
AB  - Conditions in many orphanages provide a fertile environment for infectious
      diseases uncommonly encountered in industrialized nations. Moreover, health care
      providers may be unfamiliar with the need to test for these conditions in
      internationally adopted children. Pediatric infectious disease specialists
      provide much-needed expertise for parents and providers alike.

PMID- 10079854
TI  - Travel medicine and health issues for families traveling with children.

PMID- 10079855
TI  - Infections and immunizations of children with sickle cell disease.
AB  - Children with SCD are prone to invasive infections caused by S. pneumoniae and H.
      influenzae. Osteomyelitis is caused most often by Salmonella species and less
      often by S. aureus. The chest syndrome and its associated microvascular disease
      carry a risk of prolonged and severe infections for Mycoplasma, Chlamydia, and
      probably other lower respiratory pathogens, particularly in the group of children
      with SCD prone to pain or microvascular sequestration, such as those with SC
      hemoglobinopathy. Despite three decades of investigation, the immunopathologic
      mechanisms leading to these increased risks is not completely clear. Bone
      infarction and microvascular disease probably play a part in the predisposition
      to osteomyelitis. Dysfunctional IgG and IgM antibody response, a lack of splenic
      clearance, defects in alternative pathway fixation of complement, and
      opsonophagocytic dysfunction play a role in the predisposition to invasive
      infection from polysaccharide-encapsulated organisms. Immunization with the
      conjugate Haemophilus vaccines has largely controlled infections caused by this
      pathogen. Early recognition of SCD through neonatal screening allows early and
      vigorous antibiotic management of febrile episodes in children with SCD and has
      perhaps provided the greatest benefit. Treatment of acute febrile episodes should
      include antibiotics active against regional strains of S. pneumoniae and H.
      influenzae, whereas treatment of febrile lower respiratory infections should
      include macrolide antibiotics that are active against Chlamydia and Mycoplasma,
      as well as pneumococci and Haemophilus. To date, no convincing evidence exists
      for the efficacy of pneumococcal polysaccharide vaccines in children with SCD,
      but preliminary data with the conjugate pneumococcal vaccines in normal children
      and those with SCD suggest that they may be as successful as Haemophilus vaccines
      in controlling this infection once they are available. Prophylaxis with daily
      penicillin administration is recommended and is well founded on clinical trials.
      However, problems with pneumococcal penicillin resistance and the association of
      failure with a lack of compliance to antibiotic regimens will dictate continued
      reexamination of this modality for the prevention of pneumococcal infections.

PMID- 10079856
TI  - Bacterial diarrheal pathogens.

PMID- 10079857
TI  - Animals, humans, and antibiotics: implications of the veterinary use of
      antibiotics on human health.

PMID- 10079858
TI  - [Macro- and microorganism interaction in the infection process in during
      antibacterial therapy].

PMID- 10079859
TI  - [Evaluation of antibiotic sensitivity of pathogenic vibrios of various species].
AB  - The recent increase of the number of antimicrobials and isolation of antibiotic
      resistant strains from humans and environmental objects is indicative of the
      necessity of further investigation of antibiotic susceptibility of the
      representatives of the genus Vibrio pathogenic for man to provide rational
      therapy of the diseases due to them. Susceptibility of 160 strains of pathogenic
      vibrios of 9 species to 11 antibiotics and chemotherapeutic drugs was assayed by
      the method of serial dilutions in agar media. The isolates were shown to be
      highly susceptible to chloramphenicol, doxycycline, cefotaxime, nalidixic acid
      and ciprofloxacin which made it possible to consider them as the drugs of choice
      in the treatment of the diseases caused by the microorganisms. A tendency to form
      polyantibiotic resistant strains within every species of tested pathogenic
      vibrios was observed. It conditioned the prospects of further profound study of
      the phenomenon with the analysis of the genetic determination of antibiotic
      resistance markers in pathogenic vibrios.

PMID- 10079860
TI  - [Experimental evaluation of prospects for the use of beta-lactams in plague
      infection caused by pathogens with plasmid resistance to penicillins].
AB  - High therapeutic efficacies of ceftriaxone, ceftazidime, cefotaxime and
      azthreonam in the treatment of experimental plague induced by beta-lactamase
      producing strains of the plague microbe containing R plasmids RP-1, R57b and R40a
      were shown to correlate with their in vitro antibacterial activities. The
      therapeutic efficacy of sulbactam/ampicillin was recorded in the treatment of
      plague induced by the strain containing R plasmids R57b and R40a (the treatment
      course of 7 days). However, it was lower when the infection was due to the strain
      containing plasmid RP-1 (beta-lactamase TEM-2). Cefoperazone was not active in
      the treatment of experimental plague induced by the strains containing plasmids
      RP-1 and R57b (beta-lactamases TEM-2 and OXA-3). Ceftriaxone versus the
      antibiotics tested was considered to be the drug of choice for the etiotropic
      therapy of plague induced not only by the type strains of the plague microbe but
      also by its variants with the plasmid pattern resistance to penicillins.

PMID- 10079861
TI  - [Sensitivity of Escherichia coli O157:H7, a pathogen of hemorrhagic colitis, to
      antibacterial drugs].
AB  - Antibioticograms of enterohemorrhagic strains of serogroup O157 Escherichia coli
      isolated in the Russian Federation and Japan were comparatively studied. Strains
      with multiple drug resistance were detected. The main biochemical characteristics
      of the isolates were investigated. Significant differences in susceptibility
      spectra of the isolates and in their fermentative properties were revealed.

PMID- 10079862
TI  - [Interferon-inducing action of polysaccharide-containing biopolymers from ginseng
      root and cell culture].
AB  - Induction of interferon (IF) and tumor necrosis factor (TNF) under the action of
      two polysaccharide preparations of ginseng i.e. panaxan-1 (from ginseng root) and
      panaxan-2 (from ginseng cell culture) was studied. Both the preparations induced
      production of TNF and IF in human leukocytes. By its properties and the typing
      results the induced IF proved to be gamma-IF. The preparation from the ginseng
      cell culture in the doses used had a higher IF inducing activity which could be
      explained by the difference in the polysaccharide composition of the
      preparations.

PMID- 10079863
TI  - [Antibiotic sensitivity of pneumonia pathogens in newborns and problems of
      antibacterial therapy of the pathologic process].
AB  - The results of the bacteriological investigation of the secretion from the
      trachea, large bronchi and fauces of 36 newborns (including 27 preterms) with
      severe pneumonia were analyzed. 20 of them were born of women with complicating
      somatic, obstetric and gynecologic histories: candidiasis, herpes genitalis,
      chronic endometritis, adnexitis or chronic pyelonephritis that could be the risk
      of the fetus intranatal infection. During the acute period of pneumonia in the
      newborns within the first 4-8 days of life mainly Pseudomonas aeruginosa was
      isolated (51.3 per cent), Staphylococcus epidermidis, S. haemolyticus and
      Enterococcus faecalis were less frequent (18.9, 8.1 and 5.4 per cent,
      respectively). Klebsiella pneumoniae, Streptococcus anhaemolyticus and other
      organisms were extremely rare. On the whole the gramnegative microflora
      predominated. The study of the antibiotic susceptibility showed that the majority
      of the P. aeruginosa isolates were susceptible to amikacin and polymyxin B, the
      isolates susceptible to ceftazidime were less frequent, 20-25 per cent of the
      isolates were susceptible to ciprofloxacin, cefoperazone and imipenem and
      practically no isolates were susceptible to gentamicin. The S.epidermidis
      isolates were susceptible to rifampicin and vancomycin and in rare cases to
      fusidin and amikacin and resistant to oxacillin. When the treatment course was
      more than 15 days, the isolates proved to be susceptible to 1/3 of the presently
      available antibiotics. Because of the host low protective forces, peculiarities
      of the infection pathways and high frequency of the resistant strains it is valid
      to include netilmicin, imipenem, cefoperazone and ceftriaxone to the complex
      therapy of the newborns along with the substitution immunotherapy.

PMID- 10079864
TI  - [Etiotropic antibiotic therapy and immunotherapy of patients with pyo
      inflammatory processes].
AB  - A 3-year experience was reviewed in the treatment of patients with
      pyoinflammatory processes (PIP) which developed during the postoperative period
      in 387 persons with closed injury and multiple penetrating wounds of the chest
      and stomach complicated by massive hemorrhage. When the PIP was localized in the
      abdominal cavity, enterobacteria and bacteroides were the main pathogens: 49.4 +/
      2.1 and 32.8 +/- 1.4 per cent, respectively. When the PIP was localized in the
      thoracic cavity, the most frequent pathogens were staphylococci, Pseudomonas
      aeruginosa, and enterobacteria: 26.5 +/- 1.4, 24.6 +/- 1.4 and 13.3 +/- 0.8 per
      cent, respectively. In all the cases high variability of the antibiotic
      susceptibility of the isolates and predominance of the strains resistant to 5 or
      more drugs were observed. A suppressive effect of thienam on the immune system
      was revealed. The immunocorrection in parallel with the antibiotic therapy made
      it possible to prevent further development of immune deficiency and to recover
      the bactericidal potency of the phagocyting cells. The use of various
      physiochemical methods in complex treatment of PIPs is substantiated.

PMID- 10079865
TI  - [Use of spiramycin in the treatment of inflammatory diseases ot the respiratory
      tract in children in ambulatory conditions].
AB  - Comparative efficacy of oral spiramycin and ampicillin was estimated in the
      treatment of 65 children at the age of 5 to 12 years with infectious inflammatory
      diseases of the respiratory tract, tonsils and middle ear. By the 7th day of the
      treatment with spiramycin the cure was stated in 97.7 per cent of the patients
      and 2.3 per cent of the patients showed the improvement. With the use of
      ampicillin the cure was recorded only by the 12th day. Marked advantages of
      spiramycin were observed as well with respect to the time course of the
      improvement of the disease main signs such as fever, pain in the throat on
      swallowing, intoxication and others.

PMID- 10079866
TI  - [Fluoroquinolones: importance, development of research, new drugs, questions for
      discussion].

PMID- 10079867
TI  - [Current approaches to screening novel antibacterial agents: arguments and
      discussion].

PMID- 10079868
TI  - [Organofluorine derivatives of amphotericin B: synthesis and antifungal
      activity].
AB  - Reactions of amphotericin B, a polyene macrolide antibiotic, with acyl
      perfluorides resulted in formation of its N-perfluoroacyl derivatives.
      Physicochemical and medicobiological properties of the derivatives were studied.
      The biological study revealed that the acute toxity (LD50) of the derivatives was
      2 times as low as that of the starting antibiotic. The derivatives showed high
      antifungal activity against a great number of the test cultures.

PMID- 10079869
TI  - [Effect of aeration and redox potential on the biosynthesis of the antibiotic
      imbricin].
AB  - The relationship between imbricin biosynthesis by Streptomyces imbricatus and the
      medium aeration and redox potential (Eh) was studied. The influence of the oxygen
      dissolution velocity within the ranges of 2.9 to 0.5 g O2/l.h was investigated
      and it was shown that the highest yield of the antibiotic was provided by the
      maximum velocity. At the background of the intensive aeration (2.9 g O2/l.h)
      decreasing of Eh by reducing agents such as ascorbic acid, L-thyrosin or
      K4Fe(CN)6 stimulated the biosynthesis whereas at the lower velocities the process
      proved to be inhibited. Under conditions of insufficient aeration the
      biosynthesis stimulation could be provided by increasing the medium Eh by
      acidifying agents such as K2Cr2O7, K3Fe(CN)6 or KMnO4. It was concluded that
      intensive synthesis of imbricin required not only efficient aeration but also
      definite levels of the medium redox potential.

PMID- 10079870
TI  - [Cytotoxic properties of pancreatic ribonuclease, modified by the surface active
      substance oxanol KD-6].
AB  - Pancreatic RNase modified by the surface active substance oxanole KD-6 (OxRNase)
      was studied in respect to its cytotoxic action on cells. The studies included in
      vitro and in vivo tests with intravital staining of the cells by neutral red and
      the 3H uridine label, as well as the test with the preparation action on fusion
      of lysosomes and phagosomes. It was shown that in all the tests the hydrophobised
      RNase had a higher cytotoxic action versus the native enzyme. The analysis of the
      experimental data suggested that the cytotoxicity of the hydrophobised RNase was
      due to its action on the cell membrane structures including the lysosome
      membranes.

PMID- 10079871
TI  - [Laboratory and clinical study of nitazole].
AB  - Nitazole, a drug from the nitrotiazole group, was shown to be active in vitro
      against bacteroides, peptococci, peptostreptococci, clostridia, staphylococci,
      colibacilli and streptococci. By its activity and antibacterial spectrum nitazole
      had some advantages over metronidazole, a drug from the nitroimidazole group.
      Experimental study of nitazole aerosole formulation in 4 models of purulent
      wounds of rabbits infected by Bacteroides fragilis, B. melaninogenicus,
      Clostridium perfringens 27 and Staphylococcus aureus 209P revealed its high
      therapeutic efficacy. In the treatment of 37 patients with purulent wounds of the
      soft tissues including 12 cases isolating anaerobic microbes, the clinical
      process of the acute suppuration in all the patients at the average reduced to
      the 5th-7th day. By the data of the bacteriological and cytological examinations
      the wound surface was ready for putting in stitches or free perforated cutaneous
      graft by the 10th-12th day. The drug tolerance was good. No adverse reaction were
      observed under the nitazole dressing in any case during the treatment of the
      wounds.

PMID- 10079872
TI  - [Ciprofloxacin in the therapy of severe infections in children].

PMID- 10079873
TI  - [Pharmacokinetic basis for the use of pefloxacin in severe forms of infectious
      inflammatory diseases].

PMID- 10079874
TI  - Human immunodeficiency virus gene regulation as a target for antiviral
      chemotherapy.
AB  - Inhibitors interfering with human immunodeficiency virus (HIV) gene regulation
      may have great potential in anti-HIV drug (combination) therapy. They act against
      different targets to currently used anti-HIV drugs, reduce virus production from
      acute and chronically infected cells and are anticipated to elicit less virus
      drug resistance. Several agents have already proven to inhibit HIV gene
      regulation in vitro. A first class of compounds interacts with cellular factors
      that bind to the long terminal repeat (LTR) promoter and that are needed for
      basal level transcription, such as NF-kappa B and Sp1 inhibitors. A second class
      of compounds specifically inhibits the transactivation of the HIV LTR promoter by
      the viral Tat protein, such as the peptoid CGP64222. A third class of compounds
      prevents the accumulation of single and unspliced mRNAs through inhibition of the
      viral regulator protein Rev, such as the aminoglycosidic antibiotics. Most of
      these compounds have been tested in specific transactivation assays. Whether they
      are active at the postulated target in virus replication assays has, for many of
      them, not been ascertained. Toxicity data are often lacking or insufficient. Yet
      these data are crucial in view of the toxicity that may be expected for compounds
      that primarily interact with cellular factors. Although a promising lead,
      considerable research is still required before gene regulation inhibitors may
      come of age as clinically useful agents.

PMID- 10079875
TI  - Characterization of human immunodeficiency virus type 1 resistant to modified
      cyclodextrin sulphate (mCDS71) in vitro.
AB  - Drug resistance of human immunodeficiency virus type 1 (HIV) to modified
      cyclodextrin sulphate (mCDS71) has been analysed with respect to both the in
      vitro appearance of resistance to the compound and the mechanism of the
      acquisition of resistance. Resistant strains could be obtained in all three
      strains (NL432, KK-1 and A018) tested after serial passages in MT-4 cells with a
      gradual increase of the concentration of mCDS71. Cross-resistance both to mCDS71
      and dextran sulphate 8000 was observed. As a result of sequencing analysis of the
      gp120 V3-C5 region of resistant strains, the mechanism of resistance can be
      explained in several ways: (i) substitution of sugar chain-binding amino acids, N
      and S; (ii) three to five amino acid deletion in V4 loop; and (iii) several
      mutations in V3 and V4 regions. The real cause of the resistance may be a
      combination of these three mechanisms. The results suggest that the target of
      mCDS71 is relatively widely distributed on the viral surface glycoprotein.

PMID- 10079876
TI  - PMTI, a broadly active unusual single-stranded polyribonucleotide, inhibits human
      immunodeficiency virus replication by multiple mechanisms.
AB  - Poly(1-methyl-6-thioinosinic acid), or PMTI, is a single-stranded
      polyribonucleotide and is the first homopolyribonucleotide devoid of Watson-Crick
      hydrogen bonding sites to show potent human immunodeficiency virus (HIV)
      inhibition. PMTI was found to be active when evaluated against a variety of low
      passage clinical HIV isolates in fresh human peripheral blood cells, including T
      cell-tropic and monocyte-macrophage-tropic viruses, syncytium-inducing and non
      syncytium-inducing viruses and viruses representative of the various HIV-1 clades
      (A through F). The compound was active against HIV-2, all nucleoside and non
      nucleoside reverse transcriptase (RT) inhibitor drug-resistant virus isolates
      tested and interacted with AZT or ddl to synergistically inhibit HIV infection.
      In biochemical inhibition assays, PMTI was determined to be a potent inhibitor of
      HIV-1 and HIV-2 RT, including RTs with mutations that engender resistance to
      nucleoside and non-nucleoside RT inhibitors. PMTI inhibited both the polymerase
      and RNase H activities of HIV RT. PMTI did not inhibit HIV-1 protease or
      integrase. Cell-based mechanism of action assays indicated that PMTI also
      interfered with early events in the entry of HIV into target cells. Furthermore,
      PMTI inhibited the fusion of gp120-expressing and CD4-expressing cells, but at
      concentrations approximately 1 log10 greater than those that inhibited virus
      entry. These results suggest that the homopolyribonucleotide PMTI blocks HIV
      replication in human cells at its earliest stages by multiple mechanisms,
      inhibition of virus entry and inhibition of RT.

PMID- 10079877
TI  - Fractions of chemically oversulphated galactosaminoglycan sulphates inhibit three
      enveloped viruses: human immunodeficiency virus type 1, herpes simplex virus type
      1 and human cytomegalovirus.
AB  - A series of chemically oversulphated galactosaminoglycans (SO3H:COOH ratio > or =
      2) were tested in vitro as antiviral agents against human immunodeficiency virus
      type 1 (HIV-1), the aetiological agent of AIDS, and against herpes simplex virus
      type 1 and human cytomegalovirus, two agents responsible for opportunistic
      infections in HIV-infected people. The oversulphated derivatives displayed an
      increase in activity ranging from one to four orders of magnitude against the
      three viruses, as compared to the natural parent compounds (SO3H:COOH, ratio
      approx. 1). The antiviral activity of these polyanions appears to be favoured by
      a high degree of sulphation and a high molecular mass. An oversulphated dermatan,
      with a SO3H:COOH ratio of 2.86 and molecular mass of 23.2 kDa, was the most
      potent anti-HIV-1 compound (EC50 0.04 microgram/ml). A second oversulphated
      dermatan, with a SO3H:COOH ratio of 2.40 and molecular mass of 25 kDa, displayed
      the highest activity against HSV-1 (EC50 0.01 microgram/ml). An oversulphated
      chondroitin, with a SO3H:COOH ratio of 2.80 and molecular mass of 17.3 kDa, was
      the strongest anti-HCMV agent (EC50 0.4 microgram/ml). In view of the absence of
      the side-effects typical of heparin-like compounds, a combination of these
      derivatives could have therapeutic potential.

PMID- 10079878
TI  - Synthesis of dual function (5R,6R)- and (5S,6S)-5-bromo-6-methoxy-5,6-dihydro-AZT
      5'-(para-bromophenyl methoxyalaninyl phosphate) as novel spermicidal and anti-HIV
      agents.
AB  - We synthesized a novel compound, 5-bromo-6-methoxy-5,6-dihydro-AZT-5'- (p
      bromophenyl methoxyalaninyl phosphate), which had an EC50 value of 5 microM in
      sperm motility assays. This is > 1 log10 better than that of the detergent
      spermicide nonoxynol-9 (EC50 81 microM). The compound also displayed a potent
      anti-human immunodeficiency virus (HIV) activity with an IC50 value of 0.005
      microM in HIV replication assays, which was virtually identical to that of AZT
      (IC50 0.006 microM) and > 2 log10 more potent than that of nonoxynol-9 (IC50 2.2
      microM). The promising results reported herein recommend the further development
      of the dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives as a new class
      of vaginal contraceptives capable of preventing the sexual transmission of HIV
      while providing fertility control for women who are at high risk of acquiring HIV
      by heterosexual transmission. These dual function 5-halo-6-alkoxyl-5,6-dihydro
      AZT derivatives may also have utility in curbing domestic and wildlife animal
      retroviral transmissions.

PMID- 10079879
TI  - AZT-5'-(p-bromophenyl methoxyalaninyl phosphate) as a potent and non-toxic anti
      human immunodeficiency virus agent.
AB  - The potency and selectivity index of the AZT-phenyl phosphate derivatives in
      thymidine kinase (TK)-deficient T cells were substantially enhanced by
      introducing a single para-bromo substitutent in the phenyl moiety. AZT-5'-(p
      bromophenyl methoxyalaninyl phosphate) was 43-fold more potent than AZT-5'
      (phenyl methoxyalaninyl phosphate) and was fivefold more potent than AZT in
      inhibiting human immunodeficiency virus (HIV) replication in TK-deficient CEM
      cells.

PMID- 10079880
TI  - [Infections caused by BCG and atypical mycobacteria in children: a new group of
      immune deficiencies].

PMID- 10079881
TI  - [Procalcitonin: a new marker of bacterial infection. Importance and prospects].

PMID- 10079882
TI  - [Modelization of growth between 0 and 3 years of age in children born in Toulouse
      in 1993-1994 and comparison with Sempe's growth curves].
AB  - AIM: The growth charts usually used in France were established by Sempe et al
      from the study of children born in 1953-1955. The aim of our study was to
      construct longitudinal growth charts from 0 to 3-year-old children born in 1993
      1994, and to compare those with the charts made 40 years ago. POPULATION AND
      METHODS: One hundred forty-five term neonates (75 boys and 70 girls) born in
      Toulouse in 1993-1994 were included in our study. Their heights were noted every
      3 months during the first year of life, then every 6 months until the age of 3. A
      two-stage model to modelize growth curves was used for the available data (66
      boys and 61 girls). RESULTS: Mean heights were higher in our study than in
      Sempe's. In each sex, the mean curve was 0.6 to 0.8 SD far from Sempe's mean
      curve. Standard deviations rose from 2.0 to 4.0 cm between the ages of 2 months
      and 3 years. At the age of 3, boys and girls were respectively 2.7 cm and 2.3 cm
      taller than in the Sempe's study. Differences could not be explained by sample
      bias. DISCUSSION: Constructions and publication of recent French growth charts
      seem necessary in order to be able to compare one child's growth to the growth of
      same age and sex children.

PMID- 10079883
TI  - [Neonatal screening of congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency: Lille experience 1980-1996].
AB  - AIM: The results of the neonatal screening of congenital adrenal hyperplasia due
      to 21-hydroxylase deficiency by 17-hydroxyprogesterone measurement from blood
      spot on blotting-paper in 408,138 newborns in the French Nord-Pas-de-Calais
      region from 1980 to 1996 are reported. METHODS: This measurement successively
      used a tracer tritium labelled (RIA H3), 125 iodine (RIA I125), then
      immunofluorometric method (Delfia). From 1992, sampling was systematically
      performed at the third day of life. RESULTS: Thirty-three cases were detected and
      confirmed (20 boys and 13 girls). Diagnosis was made before recalling on a
      clinical basis in three boys and eight girls. In 22 cases (17 boys and five
      girls) when diagnosis was not made before recalling, it could have been suspected
      in three girls because of a sex ambiguity once associated with dehydration and in
      eight boys because of failure to thrive (six times) or a marked dehydration
      (twice). Lack of sex ambiguity in two girls characterized non classical form of
      the illness. These two patients benefited from the early detection of the illness
      on growth data. Out of 49 subjects who died before recall, three could be
      suspected of bearing 21-hydroxylase deficiency. One single false negative case
      was found, which led to decrease cut-off value. On the other hand, false positive
      cases were frequent (0.37%), mainly in premature newborns (88% of cases).
      CONCLUSION: Although decrease of median age for recall at 7 days did not prevent
      the occurrence of two cases of dehydration, neonatal screening of 21-hydroxylase
      deficiency appears to be efficient, as far as diagnostic strategy is considered.

PMID- 10079884
TI  - [Visually handicapped children and young adults in specialized schools in the
      French North department in 1995].
AB  - BACKGROUND: In 1988, the prevalence of blindness in France was 0.17/1000 and that
      of amblyopia 0.48/1000. Medical advances in the last 30 years have modified the
      population of children with visual impairment. PATIENTS AND METHODS: The
      populations in two specialized schools of the north (340 children and
      adolescents, 3-20-year-olds) were studied and compared with the literature.
      RESULTS: Cataracts (13%) and congenital nystagmus (11%) were the two most
      frequent causes. The children taken in charge had less severe diseases than in
      the past but needed all the same specialized education. However these schools
      provided more specialized help for children educated near home, in ordinary
      schools. The children who were educated in the two specialized schools had more
      severe diseases or more social problems in their families. CONCLUSION: The
      education and educative treatment of these children are discussed.

PMID- 10079885
TI  - [Estimation of glomerular filtration rate by the formula GFR = K x T/Pc].
AB  - BACKGROUND: Creatinine clearance is the most common method used to assess
      glomerular filtration rate (GFR). In children, GFR can also be estimated without
      urine collection, using the formula GFR (mL/min x 1.73 m2) = K x height [cm]/Pcr
      [mumol/L]), where Pcr represents the plasma creatinine concentration. K is
      usually calculated using creatinine clearance (Ccr) as an index of GFR. The aim
      of the present study was to evaluate the reliability of the formula, using the
      standard UV/P inulin clearance to calculate K. METHODS: Clearance data obtained
      in 200 patients (1 month to 23 years) during the years 1988-1994 were used to
      calculate the factor K as a function of age. Forty-four additional patients were
      studied prospectively in conditions of either hydropenia or water diuresis in
      order to evaluate the possible variation of K as a function of urine flow rate.
      RESULTS: When GFR was estimated by the standard inulin clearance, the calculated
      values of K was 39 (infants less than 6 months), 44 (1-2 years) and 47 (2-12
      years). The correlation between the values of GFR, as estimated by the formula,
      and the values measured by the standard clearance of inulin was highly
      significant; the scatter of individual values was however substantial. When K was
      calculated using Ccr, the formula overestimated Cin at all urine flow rates. When
      calculated from Ccr, K varied as a function of urine flow rate (K = 50 at urine
      flow rates of 3.5 and K = 64 at urine flow rates of 8.5 mL/min x 1.73 m2). When
      calculated from Cin, in the same conditions, K remained constant with a value of
      50. CONCLUSIONS: The formula GFR = K x H/Pcr can be used to estimate GFR. The
      scatter of values precludes however the use of the formula to estimate GFR in
      pathophysiological studies. The formula should only be used when K is calculated
      from Cin, and the plasma creatinine concentration is measured in well defined
      conditions of hydration.

PMID- 10079886
TI  - [Sinus histiocytosis (Destombes-Rosai-Dorfman disease) revealed by extranodal
      spinal involvement].
AB  - BACKGROUND: Sinus histiocytosis with massive cervical lymphadenopathy (Rosai
      Dorfman disease) is a non-neoplastic lymphoproliferative disorder. Extranodal
      involvement, especially of the nervous system, is unusual. We report a case
      revealed by neurological symptoms. CASE REPORT: A 10-year-old girl presented with
      paraparesis due to a dural extramedullary mass on magnetic resonance imaging.
      Massive cervical lymphadenopathy appeared secondarily. Radiological
      investigations showed mediastinal, paranasal sinus and lower eyelid involvement.
      The diagnosis of Rosai-Dorfman disease was established histologically and by
      immunohistochemical studies of nodal lesions by the demonstration of
      characteristic sinus histiocytosis with sheets of S-100 protein and CD-68
      positive large histiocytes displaying lymphocyte phagocytosis. A dramatic
      response occurred with complete resolution of all clinical findings after
      treatment with corticosteroids and etoposide, although neurological lesions were
      unchanged on magnetic resonance imaging. CONCLUSION: Despite its rarity, this
      case underlines the unknown pathogenesis of this disease (immune dysfunction?)
      and the difficulties of treatment (choice of chemotherapeutic agents, duration).

PMID- 10079887
TI  - [Myocardial ischemia: an unknown complication of drepanocytosis in children.
      Apropos of 2 case reports].
AB  - BACKGROUND: Myocardial ischemia is a severe and unknown complication in children
      with sickle cell anemia. CASE REPORTS: Two cases of myocardial ischemia
      complicated by syncope in one (8-year-old) and cardiomyopathy in the other (3
      year-old) are reported. CONCLUSION: Chest pain in children with sickle cell
      anemia should require ECG and, in case of hypokinetic cardiomyopathy, a
      myocardial SPECT. More aggressive therapy of sickle cell anemia should be
      considered in case of documented myocardial ischemia.

PMID- 10079888
TI  - [Hematuria revealing primary hyperparathyroidism in a child].
AB  - BACKGROUND: Hematuria rarely reveals primary hyperparathyroidism in the child.
      CASE REPORT: A 10-year-old boy presented with gross hematuria and urolithiasis.
      Biological findings showed hypercalcemia and hypercalciuria. Initially,
      parathormone plasma levels remained within normal range, but raised after a few
      months and at that time, ultrasound scan examination showed a parathyroid
      adenoma. Nevertheless, two surgical explorations were necessary to cure
      hypercalcemia and hyperparathyroidism. Histological aspects of parathyroid
      adenoma were not found on pathological examination. CONCLUSION: Symptomatic
      hypercalciuria may be the first symptom revealing primary hyperparathyroidism in
      children. Surgical treatment remains difficult in such a case.

PMID- 10079889
TI  - [Congenital diaphragmatic hernia. II. Is pulmonary hypoplasia an indefinable
      obstacle?].
AB  - Despite major insights into the pathogenesis and pathophysiology of congenital
      diaphragmatic hernia, and despite the availability of an antenatal diagnosis and
      continuous progress in neonatal intensive care, little improvement has been
      obtained in the prognosis of this malformation. Thus obstetricians,
      neonatologists and pediatric surgeons are still facing a several dilemma: dilemma
      before birth to predict the prognosis, i.e., to evaluate the severity of the
      associated pulmonary hypoplasia in order to decide whether or not to interrupt
      pregnancy; dilemma after birth in case of severe respiratory failure to decide
      how far to go in life support. Based on a review of the literature and their own
      experience, the authors attempt to recapitulate the perinatal management and
      outcome of this severe malformation.

PMID- 10079890
TI  - [Hydration and meningitis].
AB  - For almost 20 years, fluid restriction has been applied in the management of
      bacterial meningitis. This recommendation was based upon the findings of elevated
      plasma levels of arginine vasopressin in children with bacterial meningitis and
      their interpretation as evidence for inappropriate secretion of antidiuretic
      hormone. Recent data indicate that this interpretation was erroneous and that
      elevated levels of arginine vasopressin is the consequence of hypovolemia in the
      majority of cases of bacterial meningitis. In addition, fluid restriction appears
      to worsen the prognosis. As a consequence, not only fluid restriction must not be
      systematically applied in the management of bacterial meningitis, but appropriate
      fluid and sodium intakes are necessary to compensate hypovolemia and dehydration.
      Only a small number of cases with evidence of inappropriate secretion of
      antidiuretic hormone will require fluid restriction.

PMID- 10079891
TI  - [Radiological case of the month. Infantile oxalosis: a rare cause of
      nephrocalcinosis].

PMID- 10079892
TI  - [Asthma in infants: current concepts].
AB  - Early childhood bronchial asthma is defined on a clinical basis as the occurrence
      of at least three episodes of wheeze before 2 years of age, once excluded a
      chronic obstructive lung disease, mainly cystic fibrosis. Recent birth cohort
      studies (Tucson, Wight island) showed that approximately 40% of early childhood
      asthma remain symptomatic in later childhood. Thus in any young child with asthma
      the question is raised of its significance, ie transient bronchial hyper
      reactivity or first manifestations of a chronic asthma. At the present time,
      there is no specific marker which may clearly differentiate between these two
      opposite evolutions, and the evidence for an atopic predisposition remains the
      best predictive criteria for persistent asthma. This justifies preventive
      measures directed towards environmental protection of the at risk young child:
      mainly passive smoking and allergen avoidance.

PMID- 10079893
TI  - [Congenital pigmented nevus: prognosis and therapeutic possibilities].
AB  - Congenital pigmented nevi are found in approximately 1% of newborn infants. Two
      main factors determine their management: 1) the risk of malignancy (melanoma); 2)
      the aesthetic consequences, these factors being themselves dependent upon the
      size and the localization of the nevi. Thus, if the systematic resection of small
      nevi is not required, early treatment of giant nevi which carry a high risk of
      malignancy before the age of ten years, is highly recommended. Main methods of
      treatment are surgical resection (with the help of skin grafts, or cutaneous
      expansion or mobilization, in giant nevi), dermabrasion and curettage.

PMID- 10079894
TI  - [Plea for prevention and early management of baby bottle tooth decay syndrome].
AB  - In spite of a spectacular drop of dental caries in children during the last ten
      years, the young child polycaries syndrome has not disappeared. Baby Bottle Tooth
      Decay is a dental pathology of temporary teeth affecting very young children,
      related to prolonged and frequent use of baby bottle with high carbohydrates
      content. The important destruction of the temporary teeth hard tissues, and the
      rapid extension of the lesions carry a high risk of infectious and orthodontic
      complications with repercussion on the permanent teeth. It is important that
      pediatricians actively participate to its prevention and early detection.

PMID- 10079895
TI  - [Viscero-atrial heterotaxia].

PMID- 10079896
TI  - [Neonatal meningitis due to Alcaligenes xylosoxidans contaminating aqueous
      solution of eosin].

PMID- 10079897
TI  - [Study of factors associated with early mortality of premature infants at the
      University Hospital Center of Brazzaville].

PMID- 10079898
TI  - [Transitory hyperinsulinism with hypoglycemia in asphyxia neonatorum].

PMID- 10079899
TI  - ["Constipation" caused by maternal milk].

PMID- 10079900
TI  - Protein and energy requirements in healthy and ill paediatric patients.
AB  - A reappraisal of available data, together with new studies, suggests that normal
      infants' energy and protein requirements might be substantially lower than
      previously estimated. For example, the safe level of protein intake would amount
      to only 10 g per day during the first 2 years of life and to about 12 g per day
      during the third. This has direct consequences for the management of malnourished
      children, particularly for defining an optimal protein:energy ratio. A reduced
      food intake has long been accepted as the main cause of malnutrition. However,
      evidence has accumulated suggesting that metabolic dysregulation may also play a
      part. This is particularly true for proteins. Net protein deposition in the
      growing child results from protein synthesis rates being higher than protein
      breakdown. However, this setting can be disrupted by a significant increase in
      protein breakdown in response to cytokines. This mechanism, which is found in
      acute as well as in chronic inflammatory processes, may lead to severe protein
      malnutrition and is not always amenable to nutritional support.

PMID- 10079901
TI  - Assessment of nutritional status in clinical practice.
AB  - As most diseases can have nutritional consequences, the assessment of nutritional
      status may help to detect an underlying disease, to identify nutritional
      disorders related to a given disease, and to quantify the impact of nutritional
      therapy. The aims and methods used for nutritional assessment depend on the
      circumstances in which nutritional assessment is performed. Whatever the context
      or aim, nutritional status is assessed through a simple, mainly clinical
      approach, based on the past history, dietary intake, auxological analysis,
      anthropometric measurements, body compartment and biological parameters. Accurate
      techniques for measuring body compartments are available in children such as dual
      energy X-ray absorptiometry to assess fat body mass or bioelectrical impedance
      analysis for body water and lean body mass. Measuring energy expenditure allows
      for a more accurate monitoring of the patient's energy needs and decreases the
      risks associated with underfeeding or overfeeding. In clinical practice, the
      analysis should be longitudinal and take into account situations carrying a risk
      of malnutrition. Preventive use of nutritional assessment allows nutritional
      support to be introduced in a timely fashion, thereby avoiding
      morbidity/mortality and limiting the long-term impact of malnutrition on growth
      and development.

PMID- 10079902
TI  - Nutritional support of infants and children: supply and metabolism of lipids.
AB  - The quantity and quality of dietary lipids and their metabolism are of major
      importance for the growth, body composition, development and long-term health of
      children, both in health and disease. Lipids are the major source of energy in
      early childhood and supply essential lipid-soluble vitamins and polyunsaturated
      fatty acids that are required in relatively high amounts during early growth.
      Lipids affect the composition of membrane structures, and modulate membrane
      functions as well as the functional development of the central nervous system.
      Some long-chain polyunsaturated fatty acids serve as precursors for bioactive
      lipid mediators, including prostaglandins, thromboxanes and leukotrienes, which
      are powerful regulators of numerous cell functions such as thrombocyte
      aggregation, inflammatory reactions and immune functions. Here we review some
      aspects of the biochemistry and physiology of lipids and their implications for
      lipoprotein metabolism, energy balance and the lipid supply during early
      childhood through the placenta, human milk, enteral diets and parenteral lipid
      emulsions.

PMID- 10079903
TI  - Nutritional management in diarrhoeal disease.
AB  - Adequate nutritional intervention in diarrhoeal disease in children is crucial in
      obtaining optimal control of a disorder that may become life-threatening. During
      recent years, important advances have been made in our understanding of the
      pathophysiology of diarrhoeal states, in the formulation of oral rehydration
      solutions and in the role of micro- and macronutrients in diarrhoeal disorders.
      This chapter outlines some of the relevant concepts in the pathophysiology of
      diarrhoeal disease and provides a rationale for nutritional intervention.
      Guidelines for nutritional management in the settings of acute-onset diarrhoea,
      post-enteritis protracted diarrhoea and chronic non-specific diarrhoea are
      provided, mostly based on controlled clinical trials and meta-analyses of
      evidence-based medicine.

PMID- 10079904
TI  - Nutrition in inflammatory bowel disease.
AB  - Nutrition is clearly disturbed by active intestinal inflammation. Appetite is
      reduced, yet energy substrates are diverted into the inflammatory process, and
      thus weight loss is characteristic. The nutritional disturbance represents part
      of a profound defect of somatic function. Linear growth and pubertal development
      in children are notably retarded, body composition is altered, and there may be
      significant psychosocial disturbance. Macrophage products such as tumour necrosis
      factor-alpha and interleukins-1 and 6 may be the central molecules that link the
      inflammatory process to this derangement of homeostasis. Intriguingly, there is
      also increasing evidence that an aggressive nutritional programme may in itself
      be sufficient to reduce the mucosal inflammatory response. Recent evidence
      suggests that enteral nutrition alone may reduce many pro-inflammatory cytokines
      to normal and allow mucosal healing. In addition, specific nutritional
      components, such as n-3 polyunsaturated fatty acids, may have an anti
      inflammatory effect as they may alter the pattern of leukotrienes generated
      during the immune response. The recent discovery of the specific molecular
      mediators of appetite and body composition, such as leptin and myostatin, may
      allow increased therapeutic specificity and further improvement in the
      nutritional treatment of the inflammatory bowel diseases.

PMID- 10079905
TI  - Short bowel syndrome.
AB  - Short bowel syndrome has significant morbidity and is potentially lethal
      especially when intestinal loss is extensive. The pathophysiology of short bowel
      syndrome, its aetiology, prognosis and our understanding of the mechanisms of
      adaptation are reviewed. Management by a multi-disciplinary nutritional care team
      is advocated and should be directed to the maintenance of growth and development,
      the promotion of intestinal adaptation, the prevention of complications and the
      establishment of enteral nutrition. The choice of enteral feed, the role of drugs
      and the use of pro-adaptive nutrients and agents are discussed. Complications
      including cholestasis and catheter related sepsis are outlined with strategies to
      reduce them. Finally the roles of secondary surgical interventions including
      transplantation are discussed.

PMID- 10079906
TI  - Motility disorders in childhood.
AB  - Motility disorders are very common in childhood, causing a number of
      gastrointestinal symptoms: recurrent vomiting, abdominal pain and distension,
      constipation and obstipation, and loose stools. The disorders result from
      disturbances of gut motor control mechanisms caused by either intrinsic disease
      of nerve and muscle, central nervous system dysfunction or perturbation of the
      humoral environment in which they operate. Intrinsic gut motor disease and
      central nervous system disorder are most usually congenital in origin, and
      alterations of the humoral environment acquired. Irritable bowel syndrome occurs
      in children as well as adults and is multifactorial in origin, with an interplay
      of psychogenic and organic disorders.

PMID- 10079907
TI  - Pancreatic diseases (excluding cystic fibrosis).
AB  - Except for cystic fibrosis, which is the most frequent genetic disorder in the
      Caucasian population, diseases of the exocrine pancreas are relatively uncommon
      in children. However, they are many and varied in terms of their pathogenesis and
      clinical manifestation. They can be classified as: (1) congenital anatomical
      abnormalities, (2) congenital secretory insufficiencies, and (3) pancreatitis. In
      all of these diseases, when pancreatic insufficiency (whether partial or
      complete) is present, the nutritional status of the patients must be investigated
      regularly, and pancreatic enzymes as well as nutritional supplementations must be
      prescribed as soon as malnutrition is present, or even prophylactically. The
      preservation of good nutritional status is the guarantee of a better prognosis.

PMID- 10079908
TI  - Cystic fibrosis: nutritional consequences and management.
AB  - Malnutrition is an adverse prognostic factor in cystic fibrosis, influencing the
      course of pulmonary disease and correlating inversely with survival. A positive
      energy balance between energy intake and the combination of total energy
      expenditure, energy losses and growth-related energy cost is essential to
      maintain normal nutritional status. Before starting nutritional supplementation,
      it is important to rule out pathological conditions that may have a deleterious
      effect on nutritional status: persistent exocrine pancreatic insufficiency,
      chronic bacterial pulmonary colonization, impaired glucose tolerance, specific
      nutritional deficits and associated disorders leading to a decrease of energy
      intake. Several methods are available, ranging from boosted oral nutrition to
      behavioural intervention, oral supplementation, enteral nutrition and, rarely,
      parenteral nutrition. The use of elemental nutrients for either oral
      supplementation or enteral nutrition seems of no nutritional benefit and is more
      expensive than conventional polymeric nutrients. Provided that the goals of the
      nutritional supplementation are fulfilled, simpler is often better.

PMID- 10079909
TI  - Cholestasis and end-stage liver disease.
AB  - Protein-energy malnutrition is an inevitable consequence of chronic liver
      disease, particularly in the developing infant. Severe malnutrition with loss of
      fat stores and muscle wasting affects between 60% and 80% of infants with liver
      disease (Beath, 1993a; Holt et al, 1997). Reduced energy intake secondary to
      anorexia, vomiting and fat malabsorption, in association with a disordered
      metabolism of carbohydrate and protein, increased energy requirements and vitamin
      and mineral deficiencies, contributes towards growth failure. Reversal of
      malnutrition is one of the key aims of liver transplantation and is achieved in
      the majority of long-term survivors. The aetiology of persistent growth failure
      post-transplantation is multifactorial and is related to pre-operative
      malnutrition, glucocorticoid administration, feeding problems and post-operative
      complications. Strategies to prevent pre- and post-transplant growth failure
      include early referral for liver transplantation and a multidisciplinary approach
      to nutritional support, which may increase survival and improve the quality of
      life and outcome of liver transplantation.

PMID- 10079910
TI  - Nutritional support in malnourished paediatric patients.
AB  - An imbalance between a person's energy requirements and his or her dietary
      protein and caloric supply is the source of protein energy malnutrition (PEM),
      which compounds the problems of any underlying disease. Malnutrition may occur
      quite rapidly in critically ill patients, particularly those suffering from
      sepsis, setting up a vicious cycle with worsening of the PEM. This chapter
      examines the main consequences of PEM, the means whereby appropriate nutrition
      may be provided, and risks for severely malnourished paediatric patients in
      hospital. If the gastrointestinal tract can be used for refeeding, it should be
      used. When the gastrointestinal tract is unable to meet the protein and energy
      requirements, parenteral nutrition (PN) is required. PN is efficient but carries
      a high risk of metabolic complications known as the refeeding syndrome and
      directly related to the homeostatic changes secondary to severe PEM. Catch-up
      growth may be achieved by using appropriate nutritional support. Changes in body
      composition have to be assessed during the course of renutrition.

PMID- 10079911
TI  - Home enteral and parenteral nutrition in children.
AB  - The prevalence of home enteral and parenteral nutrition programmes is rising
      rapidly all over the world, in children as in adults. Home artificial nutrition,
      especially parenteral nutrition, is an expensive technology but is life-saving
      for many patients. The only possible alternative to home treatment is keeping
      patients in hospital, and cost-benefit studies have demonstrated that home
      nutrition is about 70% more cost-effective than hospital-based therapy. Although
      home nutrition is usually considered by children and families to lead to an
      improvement in their quality of life, the complications of these techniques,
      including psychological consequences, have to be carefully assessed and
      prevented.

PMID- 10079912
TI  - [Electron transfer between globular proteins. Evaluation of a matrix element].
AB  - The dependence of the matrix element of the probability of interprotein electron
      transfer on the mutual orientation of the donor and acceptor centers and the
      distance between them was calculated. The calculations were made under the
      assumption that electron transfer proceeds mainly by a collective excitation of
      polaron nature, like a solvated electron state. The results obtained are
      consistent with experimental data and indicate the nonexponential behavior of
      this dependence in the case when the distance transfer is less than 20 A.

PMID- 10079913
TI  - [Electron transfer between globular proteins. Dependence of the rate of transfer
      on distance].
AB  - Based on the assumption that electron transfer between globular proteins occurs
      by a collective excitation of polaron type, the dependence of the rate of this
      process on the distance between the donor and acceptor centers with regard to
      their detailed electron structure was calculated. The electron structure of the
      heme was calculated by the quantum-chemical MNDO-PM3 method. The results were
      compared with experimental data on interprotein and intraglobular electron
      transfer. It is shown that, in the framework of this model, the electron transfer
      is not exponential and does not require a particular transfer pathway since the
      whole protein macromolecule is involved in the formation of the electron excited
      state.

PMID- 10079914
TI  - [A new approach to calculation of the energy from van der Waals interactions in
      macromolecular proteins. Dielectric permeability as a physical parameter for
      calculations].
AB  - The problem in the calculation of Van der Waals interactions in protein globules
      based on the theory of condensed media was considered. The Van der Waals
      interactions are represented as energies of interaction of regions with a uniform
      density distribution. A definition of the local dielectric constant as a function
      of coefficients of absorption of molecular groups with a particular conformation
      was introduced. The applicability of this approach was estimated. The theory
      enables one to circumvent the problems arising in calculations based on pairwise
      additive approximation. The methods provides a high accuracy in determining the
      local features of spatial structures of globular proteins and physicochemical
      characteristics of their constituent amino acids and molecular groups.

PMID- 10079915
TI  - [Quantum-chemical polyempirical study of the polymorphism of Watson-Crick pairing
      of nitrous bases].
AB  - The plurality of the geometry of complementary AT- and GC-pairs of nucleic acid
      nitrous bases was substantiated in terms of the semiempirical scheme of modified
      neglection of the differential diatomic overlap. A sixfold polymorphism of the
      Watson-Crick pairing was confirmed, which was established previously on the basis
      of simple PCILO conformational calculation. For purposes of experimental spectral
      identification of arising noncoplanar structures, the range of expected values of
      their inertial defects was determined.

PMID- 10079916
TI  - [A nonlinear mathematical model of DNA and its use in calculating neutron
      scatter].
AB  - A simple nonlinear mathematical model is applied to calculate spectrum of
      inelastic coherent scattering of neutrons by DNA.

PMID- 10079917
TI  - [Molecular mechanisms of the biological effects of weak magnetic fields. V.
      Inactivation in vitro of recombinant Rous sarcoma virus reverse transcriptase
      under the combined action of weak direct and low-frequency alternating magnetic
      fields, adjusted to the cyclotron resonance of polar amino acid ions].
AB  - The effect of weak direct and alternative magnetic fields adjusted to cyclotron
      frequencies of ions of polar amino acids leads to a functional inactivation of
      the recombinant reverse transcriptase of Rous sarcoma virus, which is coupled
      with the proteolysis of this enzyme.

PMID- 10079918
TI  - [Photosensitized inactivation of plasmid and bacteriophage lambda DNA: relative
      contribution to the lethal effect of monoadducts and diadducts of 8
      methoxypsoralen and their repair in SOS-induced Escherichia coli cells].
AB  - The curves of UV (254 nm)-inactivation and inactivation by furocoumarin
      derivatives + UVA radiation (PUVA) of bacteriophage lambda and biologically
      active plasmid pBR322 were measured using Escherichia coli K12 bacteria with
      different defects of DNA repair system as a ghost. The ratio of mono- and
      diadducts (interstrand cross-links) of 8-methoxypsoralen was determined that are
      formed after treating the DNA of pBR322 and bacteriophage lambda with PUVA. It is
      shown that, on the average, about five monoadducts per one diadduct are formed in
      DNA of pBR322, and about 0.9 monoadducts per one diadduct are formed in lambda
      phage DNA. An increased (up to 50%) efficiency of SOS-repair of monoadducts of 8
      methoxypsoralen in DNA of pBR322 and lambda in the presence of plasmid pKM101
      muc+ (incN) was found.

PMID- 10079919
TI  - [Effect of temperature on H+-K+ exchange in Escherichia coli bacteria during
      their anaerobic growth].
AB  - The H(+)-K(+)-exchange in E.coli grown under anaerobic conditions at temperatures
      from 17 to 37 degrees C was studied. The Arrhenius plots for both the N,N'
      dicyclohexylcarbodiimide-sensitive release of H+ and K+ uptake by cells
      transferred into a fresh medium containing a carbon source (glucose) are
      nonlinear. The activation energy values for the transport of these cations at
      different temperatures significantly differ. It is shown that as the temperature
      decreases, the accumulation of K+ by cells is reduced. In this process, the
      initial rate of K+ absorption through the TrkA system, the time of accumulation
      of these cations by cells and the osmosensitivity of K+ uptake substantially
      decrease. At temperatures below 20 degrees C, the absorption becomes insensitive
      to the secondary osmoshock. However, the stoichiometry of N,N'-dicyclohexylcar
      bodiimide-sensitive cation fluxes remains unchanged and is equal to 2H+:K+. It is
      assumed that the H(+)-K(+)-exchange proceeds by the operation of an ensemble of
      oligomers, formed from the protomers of F0F1 and TrkA, which rearrange by the
      action of temperature, whereas F0F1 and TrkA in each protomer do not change.

PMID- 10079920
TI  - [Change in electrokinetic potential in rat brain synaptosomes exposed to
      estradiol].
AB  - The effect of different estradiol concentrations on electrokinetic potential of
      rat brain synaptosomes has been investigated. Changes in synaptosome
      electrokinetic potential at early stages of estradiol action are shown. The data
      obtained show that synaptosomes may be used as a model system to study the
      correlation between electrokinetic potential of cells and their physiological and
      biochemical status.

PMID- 10079921
TI  - [Inhibition of growth of E. coli cells by anolites of sodium and potassium
      chloride after processing solutions in a diaphragmatic electrolyzer].
AB  - The relationship between the inhibitory effect of sodium chloride and potassium
      anolites, obtained in a diaphragm electrolyser, and the physicochemical
      parameters of solutions was compared with that between the inhibitory effect and
      physicochemical properties of hypochlorites obtained after treating the solutions
      in an electrolyser having no diaphragm was compared. The biological activity of
      solutions containing molecular chlorine, hypochlorous acid, and hypochlorite ions
      was determined by their effect on the growth of E. coli cells. After a 5-min
      incubation of cells with each of the oxidizers, the bacterial growth stopped and
      was not restored during one day. The conclusion is made that the oxidizers
      irreversibly disturb the barrier properties of cell membranes and, in some cases,
      destroy cells. In model solutions, as well as in solutions treated after heating
      on a water bath or after the addition of sodium thiosulfate, a delay in the start
      of E. coli growth occurs. After the lag-phase, the repair of cells sets on, and
      after a day the optical density of cells increases and approaches the control.

PMID- 10079922
TI  - [Effect of organic solvents on catalytic and functional activity of transport
      Ca2+,Mg2+-ATPase from smooth muscle cell membrane].
AB  - It was shown that organic solvents (dioxane, acetone, ethanol, dimethylsulfoxide)
      at concentrations of < 10% suppress the activity of transport Ca2+, Mg(2+)-ATPase
      solubilized from plasmatic membranes of smooth muscle cells and Mg(2+)-ATP
      dependent accumulation of Ca2+ ions in inverted membrane vesicles. It was found
      that one of the reasons for the inhibition of enzymatic and transport activity of
      Ca2+, Mg(2+)-ATPase by the action of these solvents is an increase in the
      attractive force between oppositely charged active center of the enzyme and the
      product (products) of the ATP-hydrolase reaction, which is induced by a decrease
      in the dielectric permeability of incubation medium.

PMID- 10079923
TI  - [Slow excitation waves and mechanisms of polymorphic ventricular tachycardia in
      an experimental model: isolated walls of the right ventricle from rabbit and
      squirrel].
AB  - The mechanism of polymorphic disturbances of the heart rhythm is studied on an
      experimental model, isolated ventricular preparations of ground squirrel and
      rabbit. Polymorphic arrhythmias are identified from habitus of the isolated
      preparation pseudoECGs mathematically derived from electrograms registered
      simultaneously at 32 endocardial and 32 epicardial points. The same electrograms
      allow one to visualize the excitation wave propagation along each of the
      preparation surfaces. The comparison of excitation wave pictures and
      corresponding pseudoECGs enabled us to reveal the conditions necessary and
      sufficient for polymorphism in heart rhythm disturbances. Polymorphic arrhythmias
      are due to changes in wave pictures in the regions of retarded excitation
      propagation.

PMID- 10079924
TI  - [X-ray structural analysis of kidney stones. Mechanism of action of pharmalith in
      nephrolithiasis].
AB  - The litholytic effect of soluran and pharmalith on renal calculi was studied by X
      ray diffraction analysis. It is shown that pharmalith is more effective in
      treating nephrolithiasis, than other drugs.

PMID- 10079925
TI  - [Asymmetry of aging of the large hemispheres of the rat brain].
AB  - The dynamics of the accumulation of free-radical oxidation products in the brain
      hemispheres of rats in rate ontogenesis was studied. Multiphase changes in the
      concentration of products in the right and left hemispheres in different age
      groups were registered. Significant differences in the contents of
      hydroperoxides, Schiff's bases of phospholipids and lipofuscin in brain
      hemispheres revealed, which correlates with different rate of ageing of
      hemispheres.

PMID- 10079926
TI  - [Physical criteria of pathological processes. II. Modulating role of functional
      interhemisphere asymmetry in forming and immune response in rheumatic diseases].
AB  - The level of the brain permanent potential as a physiological criterion of the
      functional interhemisphere asymmetry, as well as immunological and biochemical
      characteristics of peripheral blood in patients with systemic rheumatic diseases
      were studied. It was found that the distribution of the characteristics of immune
      response in patients with different types of interhemisphere asymmetry.
      Significant differences were observed for average values of biochemical and
      immunological characteristics, their dispersions, as well as for the structure of
      relationships between the type of the interhemisphere asymmetry and
      immunobiochemical characteristics.

PMID- 10079927
TI  - [Hypothesis on acoustic receptive fields].
AB  - A hypothesis of acoustic receptive fields is studied, which is based on the fact
      that the cochlea of the internal ear is a wave guide with traveling waves and the
      resonance in the critical layer. When a harmonic sound influences the ear, the
      traveling wave reaches the critical layer for the corresponding frequency and
      generates there a train of decaying waves about 25 periods in duration, which
      form a steep slope of the envelope. The funnel-shaped convergence of all neurones
      innervating the acoustic receptors of the Corti organ along the slope of the
      envelope gives rise to acoustic receptive fields. The hypothesis is consistent
      with some other experimental data. Such an acoustic receptive field makes it
      possible to use the whole train of waves in the critical layer to measure the
      frequency of the acting sinusoidal sound with the greatest possible accuracy.
      Similarly, a high accuracy of recognition of short-time sound pulses is provided,
      which could not be explained earlier.

PMID- 10079928
TI  - [The Van't Hoff rule in studying various phases of hibernation of the squirrel
      Citellus undulatus Pallas. Physico-chemical route to cold adaptation].
AB  - Taking into account the van't Hoff's law the rates of relative erythrocyte
      hemolysis in ground squirrel Citellus undulatus Pallas during different phases of
      hibernation were first studied by the method of acid erythrograms with some
      modifications. The temperature of the erythrogram registration (8 degrees C)
      models the body temperature in hibernation, and temperature of 35 degrees C,
      corresponds to the body temperature of the awakened ground squirrel. The
      positions of the erythrogram maxima for the ground squirrel during short-term
      arousal and during hibernation coincide for each temperature studied: 8 or 35
      degrees C. Therefore, the increase in HCl concentration at 8 degrees C reflects
      an increase in the stability of erythrocyte membranes or a decrease in the rate
      of relative hemolysis for the ground squirrel during hibernation. Thus, the
      adaptive response of erythrocytes in hibernating ground squirrel is revealed. The
      correlation of the rates of physicochemical processes in vitro with the rates of
      physiological ones in vivo is shown using the ratio of the rates mentioned above
      for the short-term arousal and for hibernation. First the physicochemical way of
      cold adaptation due to the van't Hoff's law is proved.

PMID- 10079929
TI  - [Film recording of the kinematics of dolphin swimming].
AB  - An ingenious method for recording the forward motion of dolphins and decoding the
      pictures was elaborated. The method makes it possible to reproduce the
      trajectories of body points of a swimming dolphin from their positions on
      pictures.

PMID- 10079930
TI  - [Is there a connection between biodiversity and the greenhouse effect].
AB  - It was discussed the role of biodiversity in ecosystems capacity to control CO2
      in atmosphere as the main reason not only of "greenhouse effect" but "greenhouse
      catastrophe". The necessity to perfect the preventive measures has been defined
      by time factor. This time may be so little for completing the evolution theory
      and models of biosphere management. The temps of contemporaneous species
      extinction exceed two orders as minimum ones how it has been known from planet
      history. It doesn't permit to discharge that evolutional process will be
      successful to create organisms which have been capable to stabilize biosphere in
      conditions of its changing status. It's possible that such change may be
      provocated with the crisis in civilization-biosphere interrelations.

PMID- 10079931
TI  - [Role of biodiversity in maintaining Earth;s climate and and human civilization.
      Problems of geobiophysics].
AB  - Factors affecting the concentration of CO2 in atmosphere were analyzed, and the
      conditions providing the Earth termal balance stability were considered. It was
      shown that the antropogenic decrease of biodiversity in climate-forming
      biosystems, such as swamps and tropical seas, may lead to the greenhouse
      disaster, resulting in the raise of the temperature on the Earth's surface up to
      300 degrees C and elimination of Life on Earth. By the example of the ecological
      disaster caused by the introduction of the European mollusc Dreissena into fresh
      waters of the North America, which was predicted by us, it was shown that the
      main reason for the decrease in biodiversity, which can accelerate the greenhouse
      disaster, is the violation of one of the Darvin principles of species formation,
      the principle of geographical isolation of species. It is shown in terms of a new
      model of periodical glaciation of the Northern Hemisphere that the elevation of
      Earth surface temperature caused by an increase in CO2 concentration in the
      atmosphere can substantially accelerate the onset of a new glaciation period in
      the Northern Hemisphere, which may decrease the greenhouse disaster rate. The
      necessity of the formation of a new interdisciplinar scientific branch,
      geobiophysics, is considered.

PMID- 10079932
TI  - [Two positions in evaluating the role of biodiversity].
AB  - The necessity is considered to use a compositional approach to the assessment of
      life phenomena in biosphere instead of, and in practice, in addition to, the
      traditional reductional approach. From this viewpoint, the construction of logics
      from top to bottom, from life as an independent system in the biosphere, to
      system elements, as it is the case in biogeochemistry and the general biological
      theory, will also appear to be necessary for biogeophysics, if such
      interdisciplinary science is destined to emerge.

PMID- 10079933
TI  - [Prospects in development of geobiophysics].
AB  - The results of the discussion about the problems of biodiversity and
      geobiophysics are summarised. The conclusion about the necessity of developing a
      new scientific branch that unites Life Sciences and Earth Sciences is drawn.

PMID- 10079934
TI  - [Inorganic phosphate is used for synthesis of phosphatidylinositol-4,5
      diphosphate].
AB  - It was shown that exogenous inorganic phosphate can be incorporated into newly
      synthesized phosphatidylinositol-4,5-bisphosphate without any participation of
      ATP.

PMID- 10079935
TI  - [Stimulation of production of tumor necrosis factor by murine macrophages when
      exposed in vio and in vitro to weak electromagnetic waves in the centimeter
      range].
AB  - Whole-body microwave sinusoidal irradiation of male NMRI mice, exposure of
      macrophages in vitro, and preliminary irradiation of culture medium with 8.15-18
      GHz (1 Hz within) at a power density of 1 microW/cm2 caused a significant
      enhancement of tumor necrosis factor production in peritoneal macrophages. The
      role of microwaves as a factor interfering with the process of cell immunity is
      discussed.

PMID- 10079936
TI  - [Absence of seasonal adaptive changes in the isoformic state and functional
      properties of actin-containing and thin filament proteins in skeletal muscles of
      hibernating squirrels].
AB  - The data indicating the absence of seasonal changes in the isoform composition
      and functional properties of actin and thin filament associated proteins from
      skeletal muscles of hibernating ground squirrels were obtained. Taking into
      account the data obtained earlier by the authors on significant qualitative and
      quantitative changes in isoform composition and functional properties of the
      other contractile protein, myosin, it is concluded that the suppression of
      contractile capacity of the executive apparatus of skeletal muscles of animals
      upon hibernation and its repair upon arousal are determined by the above adaptive
      changes in myosin.

PMID- 10079937
TI  - [Deglycosylation of glycoproteins].
AB  - Glycosylation procedures and their application for the elucidation of
      glycoprotein structure and structure-function relations, as well as for the
      development of analytical systems for clinical practice are reviewed. For some
      common cases found in research practice, the choice of optimal deglycosylation
      methods is discussed. Current views on the primary structure of glycoproteins are
      described briefly.

PMID- 10079938
TI  - [Study of structure of secretory 28 kDa protein from the rat olfactory
      epithelium].
AB  - Clone lambda a26.1 isolated from rat olfactory epithelium contains a full-length
      28-kDa protein cDNA (1414 b.p.). The reconstructed protein sequence comprises 223
      aa with a calculated molecular mass of 24,630 Da. A substantial homology was
      revealed between the amino acid sequence of the 28-kDa protein and those of thiol
      specific antioxidants (peroxiredoxines). The 28-kDa protein belongs to the 1 Cys
      subfamily of peroxiredoxines and is the first member of peroxiredoxines
      identified in the olfactory epithelium.

PMID- 10079939
TI  - [Fungal aspartic proteinase from Trichoderma viride. Specificity during
      oligopeptide hydrolysis].
AB  - We isolated, purified, and characterized an aspartic protease from fungus
      Trichoderma viride. The pH-dependence of the enzyme functioning was determined,
      and its specificity in the limited proteolysis of insulin and melittin was
      compared to the specificities of pepsin A and gastricsin. The kinetics of
      melittin hydrolysis by these enzymes was studied by mass spectrometry.

PMID- 10079940
TI  - [Sensitized photomodification of DNA with binary systems of oligonucleotide
      conjugates. III. Double-quantum sensitization].
AB  - Site-specific modification of single-stranded DNA by oligonucleotide derivatives
      of p-azido-O-(4-aminobutyl)tetrafluorobenzaldoxime sensitized by an
      oligonucleotide derivative of pyrenylethylamine was studied. Upon irradiation
      with the long-wave UV light (365-390 nm) of a DNA target-oligonucleotide reagent
      complementary complex, a considerable increase in the rate of sensitized
      photomodification at the G11 residue of the target relative to the direct
      photomodification was observed owing to the singlet-single energy transfer from
      the sensitizer onto the photoreagent. Upon simultaneous irradiation of the
      complex with UV and visible light in the region of the triplet-triplet absorption
      of pyrene (360-580 nm), an additional increase in the modification rate and a
      change in its site-direction (from the G11 to T13 residue) occurred through the
      two-photon triplet-triplet sensitization. The total extent of the structure
      photomodification amounted to 80%.

PMID- 10079941
TI  - [Structure of glycerophosphate-containing O-specific polysaccharide from
      Pseudoalteromonas sp. KMM 639].
AB  - On the basis of acid hydrolysis, dephosphorylation, methylation, and 13C NMR
      spectroscopy data, the O-specific polysaccharide of Pseudoalteromonas sp. KMM 639
      was shown to be a glycerophosphate-containing polymer built of repeating
      disaccharide units of the following structure: [formula: see text]

PMID- 10079942
TI  - [Physico-chemical properties of borate derivatives of DOPA, dopamine, and their
      liposome forms].
AB  - To increase the solubility of L-3,4-dihydroxyphenylalanine (DOPA) and dopamine
      (DA) incorporated in liposomes, it was suggested to convert them into ammonium
      and 1-adamantylammonium borate complexes. The structure of these complexes was
      studied by 11B and 1H NMR, IR, and mass spectrometry and conductometry. The
      liposomic form of the complexes is characterized by a high active compound/lipid
      molar ratio (0.5). Catechols in the form of complex salts are retained better
      within the inner volume of liposomes.

PMID- 10079943
TI  - [Composite fluorine polymer-containing sorbents for isolation and purification of
      biopolymers].
AB  - Composite fluoropolymer-containing sorbents based on porous silicas were
      synthesized for the isolation and purification of biopolymers under nondenaturing
      conditions. Examples of the application of these sorbents in the separation of
      various mixtures of peptides and proteins and purification of nucleic acids from
      various sources (plasmid DNA and DNA from nucleated human blood cells) using the
      cartridge, column, and batch (sorption in a stirred volume) methods are
      presented. It was shown that the sorbents can be used in laboratory practice
      because they are selective to nucleic acids (DNA and RNA) and proteins. These
      materials combine the mechanical properties of the inorganic matrix with the
      specific sorption properties of the polymer phase and exhibit enhanced stability
      to alkaline hydrolysis. Alternative methods of preparing sorbents containing
      polytetrafluoroethylene, polytrifluorostyrene, and polyfluorobutadiene are
      described. By the example of polyfluorobutadiene-containing sorbents, a
      completely new method for obtaining fluorinated polymer phases was developed: the
      polymer phase was preliminarily formed on the surface of porous disperse carriers
      and was fluorinated with xenon difluoride.

PMID- 10079944
TI  - [Molecular identification and characteristics of hRPC11, the smallest specific
      subunit of human RNA polymerase III].
AB  - Full-length copies of cDNA of the hRPC11 gene encoding the smallest specific
      subunit of nuclear RNA polymerase III were identified among human transcripts
      with the use of the RT-PCR technique. The cloning of the first orthologue of the
      subunit RPC11 from a multicellular organism and the comparison of subunit hRPC11
      of Homo sapiens (108 aa; M(r), 12.3 kDa; pI 8.05) deduced from the cDNA primary
      structure with the homologous components of RNA polymerase III from Saccharomyces
      cerevisiae and Schizosaccharomyces pombe revealed the most important functional
      domains: a Zn-binding motif of the classic type (CxxCx16-17CxxC) at the N
      terminal region, and two extended regions of homology (KEVDDVLGG and RSADEPM) in
      the central and C-terminal parts of the molecule, respectively. The C-terminus of
      the RPC11 subunits is highly homologous to the unique zinc ribbon of the
      elongation factor TFIIS, which suggests a role for this subunit in the elongation
      or termination of RNA synthesis.

PMID- 10079945
TI  - [Features of the structural organization of inactivated actin--an intermediate
      form of the protein during the folding-unfolding process].
AB  - The structure of inactivated actin was studied by the methods of intrinsic
      fluorescence upon stationary and pulse excitation, selective fluorescence
      quenching with acrylamide, and testing the protein surface with a hydrophobic
      probe, 8-anilino-1-naphthalenesulfonic acid (ANS). The results are discussed
      along with earlier data on actin sedimentation, near- and far-UV CD spectra, and
      fluorescence anisotropy. The thermodynamic stability of inactivated actin, the
      presence of a secondary structure characteristic of the native protein, and the
      reversibility of the inactivated actin-completely unfolded actin transition allow
      inactivated actin to be considered an intermediate form in the process of protein
      folding into the native globular structure. In vitro actin inactivation is
      accompanied by specific association of actin macromolecules resulting in the
      formation of homogeneous stable complexes. The tendency toward aggregation (or
      specific association, in the case of actin), which is determined by the presence
      of extended hydrophobic clusters on the molecule surface, appears to be one of
      the intrinsic properties of any protein in the intermediate state. The mobility
      of the amino acid side chains in the inactivated actin differs considerably from
      that in the completely unfolded actin. The relaxation properties of the
      microenvironment of tryptophan residues determine relatively long-wave
      fluorescence spectra of the inactivated actin. However, the mobility observed is
      insufficient to compensate the asymmetry of the microenvironment of aromatic
      residues, which is confirmed by a characteristic and intense CD spectrum in the
      near-UV region. The mobility of the indole rings of tryptophans located in the
      internal regions of the inactivated actin that are solvent-inaccessible although
      polar is even considerably lower than that in the native actin.

PMID- 10079946
TI  - [Intrinsic fluorescence of globular actin. Features of localization of tryptophan
      residues].
AB  - The contribution of individual Trp residues to alpha-actin fluorescence was
      evaluated by means of an analysis of their microenvironment, which was done on
      the basis of PIR-International protein sequence database information. The
      contribution of Trp79 and Trp86 was shown to be low due to an effective
      nonradiating energy transfer according to the inductive resonance mechanism
      between the Trp residues and the fluorescence quenching of Trp86 by S gamma of
      Cys10, an efficient fluorescence quencher. The intrinsic fluorescence of actin
      was found to be determined mainly by Trp340 and Trp356, which are internal,
      inaccessible to solvent, and have a high density microenvironment formed mainly
      by nonpolar groups of protein. It is possible that the side chain conformation of
      Trp340 (t-isomer; chi 1 190 degrees, chi 2 89 degrees), aromatic rings of Tyr and
      Phe residues, and Pro residues in the microenvironment of Trp340 and Trp356
      substantially contribute to the short-wavelength fluorescence spectrum of actin.

PMID- 10079947
TI  - [Synthesis and immunogenic properties of peptides--fragments of the
      immunodominant regions of the VP1 protein of the Asia-1 type of foot- and-mouth
      disease virus].
AB  - Potential immunodominant epitopes were predicted on the basis of a theoretical
      analysis of the antigenic structure of the VP1 protein of the type Asia-1 foot
      and-mouth disease virus. Peptides corresponding to the 140-153, 136-153, 132-153,
      143-157, 137-157, and 193-208 fragments of the VP1 protein sequence were
      synthesized by the solid phase method, and the immunogenic properties of the
      peptides were studied on guinea pigs. The shortest peptide exhibiting the
      protective effect was found to correspond to the, 140-153 fragment of the VP1
      sequence. The Plm-(Gly)3-(140-153)-(Gly)2-Lys(Plm)-Leu and [Ac-(140-153)-(Gly)3]8
      (Lys)7-Gly synthetic constructions in combination with adjuvants provided up to
      80% protection of immunized animals against infection with the foot-and-mouth
      disease virus.

PMID- 10079948
TI  - [Cloning and determining the primary structure of fragments of the RNA-polymerase
      beta-subunit genes from representatives of Baikal picoplankton].
AB  - Fragments of the RNA polymerase beta-subunit genes from representatives of
      picoplankton of Lake Baikal were cloned using polymerase chain reaction (PCR),
      and the resulting recombinant clones were sequenced. An analysis of 93 clones
      revealed 40 different sequences. A comparison of these nucleotide sequences and
      the corresponding amino acid sequences deduced with their homologues from
      databanks confirmed the high conservation of the RNA polymerase beta-subunit
      region involved in the formation of the enzyme active site.

PMID- 10079949
TI  - [Cloning of region-specific genetic markers of planaria using a new method-
      ordered differential display].
AB  - A new method for finding differentially expressed genes, termed ordered
      differential display of mRNAs (ODD), was used in the search for region-specific
      molecular markers of freshwater planarian Dugesia tigrina. In this method, the
      effect of selective suppression of a polymerase chain reaction (PCR) is used for
      the differential amplification of a pool of 3'-terminal cDNA fragments generated
      by digestion of cDNAs with a restriction endonuclease. In the resulting amplified
      cDNAs, every mRNA is represented by a cDNA fragment whose length is determined by
      the position of the restriction site nearest to the 3'-terminus. Subsequent PCR
      with primers 3'-extended by two random nucleotides allowed the amplification of
      1/192 part of all cDNA molecules present in the sample. The comparison of the
      generated pools of cDNA molecules separated by PAGE leads to the identification
      of differentially expressed sequences. The systematic study of the total mRNA
      pool is achieved by the successive use of all possible combinations of extended
      primers. Some sequences preferentially expressed along the anterior-posterior
      axis of planarian were identified using ODD.

PMID- 10079950
TI  - [Chemical modification of eukaryotic cell chromatin, directed at d(GT)n-repeats
      of DNA].
AB  - DNA and proteins of chromatin from eukaryotic cells were specifically modified by
      an alkylating derivative of pd(AC)6 (complementary to d(GT) repeats of DNA)
      containing a 4-(N-methyl-N-2-chlorethylamino)benzylamine residue on its 5'-end.
      It was shown that the efficiency of modification of both DNA and proteins
      increases in the presence of spermine and spermidine and sharply decreases after
      preliminary treatment of chromatin by nuclease S1 under conditions of mild
      cleavage of single-stranded DNA regions. It was suggested that one of the reasons
      for the presence of unwound d(GT)n stretches in chromatin DNA accessible for
      interaction with the complementary oligonucleotide is the B-->Z transition.
      Proteins specifically alkylated within the chromatin, which most likely are
      located in the regions of local unwinding of DNA, near the repeats, were
      analyzed.

PMID- 10079951
TI  - [A new inhibitor of pyrimidine phosphorylase].
AB  - 5,5-Bis(hydroxymethyl)-2-oxo-[1-(2-trifluoromethyl)-3,3,3- trifluoropropionamido)
      1-trifluoromethyl-2,2,2-trifluoroethyl- 1,3,2-dioxaphosphan (CA-423) is an in
      vitro inhibitor of the Escherichia coli uridine and thymidine phosphorylases.
      Unlike widely studied nucleoside analogues, this compound binds to the enzymes
      irreversibly. Its LD50 in mice was 40 mg/kg. Due to the involvement of pyrimidine
      phosphorylases in carcinogenesis and the relatively low toxicity of CA-423, it is
      promising for anticancer therapy.

PMID- 10079952
TI  - [Molecular cloning and characteristics of rpc19+ and rpc40+ Schizosaccharomyces
      pombe genes, coding for common subunits of nuclear RNA polymerase I and III].
AB  - Full-length copies of cDNAs of the rpc19+ and rpc40+ genes encoding the common
      subunits of nuclear RNA polymerases I and III and the corresponding fragments of
      chromosomes were isolated from genomic and cDNA libraries of Schizosaccharomyces
      pombe and characterized. It was established that the cloned genes are located on
      chromosomes III and II of the fission yeast, respectively. The rpc40+ gene lacks
      introns, and the rpc19+ gene contains two intervening sequences. The comparison
      of subunits Rpc19 (125 aa; M 13 722 Da; pI 4.51) and Rpc40 (348 aa; M 39 141 Da;
      pI 5.40) of Sz. pombe, whose characteristics were deduced from the sequences of
      their cDNAs, with the orthologous components of other eukaryotes allowed the most
      conserved structure-functional domains of these proteins to be identified.

PMID- 10079953
TI  - Clinical and cost effectiveness of post-acute neurobehavioural rehabilitation.
AB  - The value of post-acute, community based social and behavioural rehabilitation
      for people with serious neurobehavioural disability has been the subject of a
      dispute for a number of years. Some authorities doubt that major changes in
      social adaptability and independence is possible several years post-injury. This
      paper attempts to assess both the clinical and cost effectiveness of such
      rehabilitation on a group who have suffered serious brain injury and display
      behaviour problems and cognitive deficits which prevent them living as
      independent members of the community. The discharge and follow-up data on 76
      people who have received rehabilitation indicates that, with a minimum of 6
      months rehabilitation, many severely damaged individuals can progress to less
      dependent placements in the community, and maintain higher levels of social
      activity (independence) with fewer hours of care support. This can amount to a
      per capita lifetime reduction of over 1 million pounds per annum in the cost of
      supporting such people in the community. Time between injury and the beginning of
      rehabilitation is a factor influencing outcome but longer periods of
      rehabilitation (beyond 12 months for the most seriously disabled) is not
      associated with a better outcome, measured by a reduction in care hours. The cost
      effectiveness of rehabilitation is greater for those who receive treatment within
      2 years of injury. However, those who received rehabilitation at later stages
      also achieved significant social outcomes and savings on care hours.

PMID- 10079954
TI  - Incidence of sexual dysfunction in TBI patients during the early post-traumatic
      in-patient rehabilitation phase.
AB  - OBJECTIVE: The aim of the study is to find whether sexuality and intimacy
      dysfunction are already present at the early rehabilitation phase of TBI
      patients. METHODS: Forty-four consequent severe TBI patients were studied. The
      GCS and the duration of unconsciousness determined the initial severity of the
      injury. Patients' function regarding motor, language, cognition and behaviour
      were assessed by an interdisciplinary team. Sexuality and intimacy were evaluated
      by using a special closed questionnaire. RESULTS: Regarding self confidence 81%
      of patients described themselves as having high or average self confidences; 78%
      described themselves as having high or average feeling of being sexually
      appealing; mood level was average or high in 80% of patients. Only 7.7% of
      patients reported having sexual dysfunction at that phase of rehabilitation.
      CONCLUSIONS: Sexual dysfunction in Severe TBI patients is uncommon at the early
      post-traumatic phase. It is suggested that sexual dysfunction appearing during
      later stages of recovery is most probably related to reactive behavioural
      changes.

PMID- 10079955
TI  - Assessing auditory comprehension in the context of severe physical disability:
      the PACST.
AB  - Existing tests of auditory comprehension are frequently unsuitable for patients
      with physically disabling conditions as tests require skills such as physical
      manipulation of materials. A suitable test is required to assess the reliability
      and validity of responses in patients who can only indicate 'yes' and 'no'. This
      has implications for enabling patients to participate, for example, in decision
      making over their care. In the construction of the Putney Auditory Comprehension
      Screening Test (PACST) 200 normal participants were tested with 258 yes/no
      questions. From their results a test consisting of 60 unambiguous questions,
      varying in difficulty, type, syntactic complexity and length were selected. A
      clinical trial was completed with 112 patients from the Royal Hospital for Neuro
      disability. The 60 item test was found to be reliable and valid. Results were
      also compared with independent ratings by ward managers and speech and language
      therapists. Effects of demographic variables were as expected. A 60 question test
      was developed which was shown by the clinical trial to be a useful tool.
      Questions vary in difficulty, but not enough to establish a difficulty gradient.
      On the basis of performance on the test, patients can be allocated to three
      groups: normal, impaired, and chance performance.

PMID- 10079956
TI  - Psychosocial outcome risk indicator: predicting psychosocial outcome following
      traumatic brain injury.
AB  - This study examines the outcome of 29 individuals with traumatic brain injury
      (TBI) and 23 of their respective significant others, 12 months after discharge
      from inpatient rehabilitation services, as a means of determining the validity of
      a measure developed to predict psychosocial outcome. This measure consists of 18
      questions that examine 12 factors and requires the rater to make a judgement
      about the likely impact each factor would have on the individual with TBI and
      significant other. Results indicate that the social work raters accurately
      predicted outcome according to the factors contained in the measure. Scores on
      the measure at discharge were also found to be associated with general
      psychological distress, anxiety and insomnia, depression, family functioning, and
      the problems related to emotion and behaviour. Although the sample size was
      small, there is an indication that the devised measure is useful in predicting
      outcome and so has clinical value in identifying adults at greatest risk of poor
      psychosocial outcome after a traumatic brain injury.

PMID- 10079957
TI  - The usefulness of the Brief Symptom Inventory in the neuropsychological
      evaluation of traumatic brain injury.
AB  - Changes in the health care delivery system are forcing clinicians to use less
      timely and more cost efficient measures. In rehabilitation, more efficient
      measures of emotional-behavioural functioning are being administered to patients
      with traumatic brain injury (TBI), including the Brief Symptom Inventory (BSI), a
      53 item short version of the Symptom Checklist-90 that assesses nine different
      dimensions of emotional-behavioural functioning. Because the BSI was developed
      for use with psychiatric populations, research of the measure with TBI
      populations is needed. The current study evaluated the utility of the BSI in a
      sample of 62 patients (34 male, 28 female, average age 35, average education 12
      years) with TBI evaluated as outpatients at a midwestern rehabilitation hospital.
      Results indicated that: (1) subjects endorsed clinically elevated distress on
      seven of the nine subscales when compared to the normative sample; (2) the
      Obsessive-Compulsive (OC) subscale achieved the highest t-score (70.31); 3) the
      most frequent two-point profiles included the OC-Somatic (21%) and OC
      Psychoticism (13%) subscales; and (3) the Global Symptom Index was significantly
      correlated with all nine subscales. It was concluded that caution must be used
      when administering the BSI to individuals with TBI due to a lack of a TBI
      standardization sample, the limited number of test items per subscale, and
      questionable labels for the different subscales (e.g. OC subscale items appear to
      be more reflective of TBI-related cognitive impairment than obsessive-compulsive
      traits).

PMID- 10079958
TI  - Major life events as risk factors for post-stroke depression.
AB  - Depression is a significant sequela of stroke which contributes to increased
      morbidity and mortality in stroke survivors. Psychosocial stressors, such as
      major life events, pose risk factors for developing depression in non-stroke
      populations. This study evaluated major life events as a risk factor for
      developing post-stroke depression (PSD) during the first year post-stroke. One
      hundred and eleven patients who completed the Center for Epidemiological Studies
      Depression Scale at four time periods during the first year post-stroke were
      assessed for PSD and asked if they had experienced a major life event in the
      prior 6 months (other than the stroke). The subjects completed the evaluations
      acutely (7-10 days), and at 3, 6, and 12 months post-stroke. At 6 months post
      stroke patients were significantly more likely to be depressed if they had a
      major life event in the prior 6 months (other than the stroke) than if they had
      not, chi 2 (df = 1) = 4.83, p < 0.028, relative risk = 2.31, 95% confidence
      interval 1.15-4.62. Life events pose significant risks for developing PSD at 6
      months post-stroke. Stroke patients need to be asked about these events and
      treated for PSD.

PMID- 10079959
TI  - Rehabilitation outcomes in encephalitis--a retrospective study 1990-1997.
AB  - BACKGROUND: Encephalitis is an uncommon clinical entity compared to traumatic
      brain injury, and stroke. Many encephalitis survivors have disabling sequelae.
      There is scant information in the literature addressing outcome following
      inpatient rehabilitation for encephalitis. Further, it is unclear which of these
      patients will benefit from acute in-patient rehabilitation. PURPOSE: The purposes
      of this study are to (1) describe the outcome following in-patient rehabilitation
      in a cohort of patients with encephalitis, and (2) develop preliminary criteria
      to guide the selection of patients with encephalitis who may benefit from
      inpatient rehabilitation. METHOD: The demographic, clinical, functional
      (functional independence measure-FIM) and neuro-psychological data were
      retrospectively abstracted for eight subjects with a clinical diagnosis of
      encephalitis aged 5 to 75 years, who were admitted to a brain injury
      rehabilitation unit between 1990 and 1997. RESULTS: In the eight subjects, the
      mean age was 38 years, mean acute hospital stay (ALOS) was 40.3 days, and mean
      rehabilitation length of stay (RLOS) was 75.9 days. Mean admission FIM (AFIM) was
      40.1, mean discharge FIM (DFIM) was 69.9. Mean FIM gain was 29.8 and mean FIM
      efficiency was 0.39. Adult subjects with an AFIM > 30 at 5 weeks from onset of
      illness (n = 4) had a FIM LOS efficiency of 0.64 and all four were discharged
      home. None of the adult subjects with an AFIM < 30 at 5 weeks from onset of
      illness (n = 3, FIM efficiency = 0.14) were discharged home. A child with an AFIM
      < 30 (n = 1) had a FIM LOS efficiency of 1.24, made good recovery and was
      discharged home. FIM LOS efficiency of 0.64 in encephalitis is less, as compared
      to traumatic brain injury (TBI -1.27) and stroke (1.06). CONCLUSIONS: The results
      of this study showed that, although subjects with encephalitis make functional
      gains in rehabilitation, the rate of recovery varies and is generally less than
      that for TBI and stroke. The study also suggests that FIM scores can be used for
      screening adult patients after encephalitis for admission to inpatient
      rehabilitation. Adult patients with an AFIM > 30, 5 weeks post onset of illness
      are likely to make reasonable progress and be discharged home. If replicated,
      these results suggest that despite low AFIM scores at 5 weeks from onset of
      illness (AFIM < 30), children may still make good progress and should be given a
      trial of in-patient rehabilitation.

PMID- 10079960
TI  - Utility of a microcomputer as an external memory aid for a memory-impaired head
      injury patient during in-patient rehabilitation.
AB  - Memory deficit is one of the most frequent cognitive complications encountered
      after brain injury. It is recognized as difficult to treat. Over the past
      decades, various strategies of memory remediation have been used. Among them,
      prosthetic devices, such as notebooks and alarms, have shown some benefit. This
      study describes the case of a 22-year-old man who demonstrated deficits in memory
      and executive function. In an in-patient rehabilitation setting, a microcomputer
      was introduced as an external memory aid. With this intervention, the patient
      demonstrated an immediate improvement in the ability to attend every therapy and
      ask for every medication on his schedule. This case study demonstrates the
      usefulness of a microcomputer as an external memory aid for a memory-impaired
      head injury survivor.

PMID- 10079961
TI  - Application of a novel technique for clinical evaluation of nitric oxide-induced
      free radical reactions in ICU patients.
AB  - 1. We recently developed a new technique for measuring serum NO2 and NO3 levels
      precisely, and we examined these parameters in severely brain-injured ICU
      patients who could not take nutrition intestinally. 2. Our results demonstrated
      that NO increased rapidly after stroke, trauma, and the occurrence of infection
      in all ICU patients. Elevation of NO2/NO3 was most pronounced 24 to 48 hr after
      trauma or ischemic stroke. This dysregulation of free radical elimination closely
      correlated with hemoglobin levels. 3. In most ICU patients, with the exception of
      those with complications of infection, the free radical potentials were maximal
      at 24 to 48 hr and continued to remain high for 4 to 5 days after trauma or
      stroke. The level of free radical potentials was closely correlated with the
      severity and prognosis of critically injured patients. None with radical
      potential values higher than 0.4 microM survived. 4. Clinically, the maintenance
      of hemoglobin at > 12 g/dl and lower body temperature were demonstrated to be
      successful in the management of these free radical reactions.

PMID- 10079962
TI  - Is there a genetic basis for the deposition of beta-amyloid after fatal head
      injury?
AB  - 1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic
      or environmental factors or by a combination of both. Abnormalities in
      chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the
      early-onset form of the disease, while the epsilon 4 allele of the apolipoprotein
      E gene (on chromosome 19) is now recognized as a risk factor for early- and late
      onset sporadic and familial Alzheimer's disease. 2. The best-established
      environmental trigger for the disease is a head injury, based on epidemiological
      and neuropathological evidence. Approximately 30% of patients who die after a
      single episode of severe head injury show intracerebral deposition of beta
      amyloid protein (A beta), a protein that is thought to be central to the
      pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over
      representation of the apoE epsilon 4 allele in those head-injured patients
      displaying A beta pathology, thus providing the first evidence for a link between
      a genetic susceptibility (apoE epsilon 4) and an environmental trigger (head
      injury) in the development of Alzheimer-type pathology.

PMID- 10079963
TI  - Antioxidant therapy against cerebral vasospasm following aneurysmal subarachnoid
      hemorrhage.
AB  - 1. Approximately one-third of the morbidity and mortality due to aneurysmal
      subarachnoid hemorrhage (SAH) is caused by delayed ischemic neurological deficit
      (DIND) due to cerebral vasospasm. 2. Compared to prolonged arterial constriction
      in other parts of the body, cerebral vasospasm is characterized by its long
      duration and refractoriness to vasodilators such as calcium antagonists. 3.
      Whereas oxyhemoglobin (oxyHb) liberated into the CSF from the subarachnoid clot
      has been deemed the causative agent of vasoconstriction, the biochemical
      mechanisms whereby oxyHb elicits prolonged constriction of the cerebral arteries
      has remained elusive. Here, we suggest that oxyHb triggers the generation of
      reactive oxygen intermediates (ROI) within the CSF. 4. Multiple lines of evidence
      indicate that the occurrence of vasospasm, namely, prolonged smooth muscle
      contraction, is due to the following intracellular events. 5. First, hydroxyl
      radicals (OH*), the most reactive species of ROI, are generated within the
      cerebral arterial wall via the Fenton and Haber-Weiss reactions catalyzed by
      oxyHb. Second, subsequent peroxidative membrane damage in the arterial smooth
      muscle cell enhances the metabolism of phosphatidylcholine and
      phosphatidylethanolamine, leading to a rise in the intracellular level of
      diacylglycerol, an endogenous activator of protein kinase C. 6. The prolonged
      arterial contraction that occurs during vasospasm is attributable primarily to
      the activation of protein kinase C, not to the Ca2+/calmodulin system. In this
      article, literature relevant to the above thesis is reviewed, and the rationale
      for the antioxidant therapy against cerebral vasospasm is discussed.

PMID- 10079964
TI  - Carnosine: an endogenous neuroprotector in the ischemic brain.
AB  - 1. The biological effects of carnosine, a natural hydrophilic neuropeptide, on
      the reactive oxygen species (ROS) pathological generation are reviewed. 2. We
      describe direct antioxidant action observed in the in vitro experiments. 3.
      Carnosine was found to effect metabolism indirectly. These effects are reflected
      in ROS turnover regulation and lipid peroxidation (LPO) processes. 4. During
      brain ischemia carnosine acts as a neuroprotector, contributing to better
      cerebral blood flow restoration, electroencephalography (EEG) normalization,
      decreased lactate accumulation, and enzymatic protection against ROS. 5. The data
      presented demonstrate that carnosine is a specific regulator of essential
      metabolic pathways in neurons supporting brain homeostasis under unfavorable
      conditions.

PMID- 10079965
TI  - Molecular biology of catecholamine-related enzymes in relation to Parkinson's
      disease.
AB  - 1. Catecholamine (dopamine, norepinephrine, and epinephrine) biosynthesis is
      regulated by tyrosine hydroxylase (TH). TH activity is regulated by the
      concentration of the cofactor tetrahydrobiopterin (BH4), whose level is regulated
      by GTP cyclohydrolase I (GCH) activity. Thus, GCH activity indirectly regulates
      TH activity and catecholamine levels. 2. TH activity in the nigrostriatal
      dopaminergic neurons is most sensitive to the decrease in BH4. 3. Mutations of
      GCH result in reductions in GCH activity, BH4, TH activity, and dopamine, causing
      either recessively inherited GCH deficiency or dominantly inherited hereditary
      progressive dystonia [HPD; Segawa's disease; also called dopa-responsive dystonia
      (DRD)]. 4. In juvenile parkinsonism and Parkinson's disease, which have dopamine
      deficiency in the basal ganglia as HPD/DRD, the GCH gene may be normal, and the
      molecular mechanism of the dopamine deficiency in the basal ganglia is different
      from that in HPD/DRD.

PMID- 10079966
TI  - Neural transplantation for Parkinson's disease.
AB  - 1. Neural transplantation is one promising approach for the treatment of
      Parkinson's disease. Fetal substantia nigra cells are a good source of dopamine,
      but in order to avoid ethical and immunological problems, adrenal medullary
      chromaffin cells have been investigated as an alternative source. 2. Grafted
      adrenal medullary chromaffin cells can provide dopamine as well as several
      neurotrophic factors that affect dopaminergic neurons in the brain. 3. We review
      experimental studies for application of neural transplantation techniques in
      Parkinson's disease, including immunological studies, cryopreservation,
      microvasculature, donor tissue, and direct gene delivery studies performed in our
      laboratory. Our clinical experience and new approach involving a polymer
      encapsulated cell grafting procedure are also described.

PMID- 10079967
TI  - Successful survival of grafted transgenic neural plate cells in adult central
      nervous system environment.
AB  - 1. Accumulating evidence indicates that damaged brain functions can be
      ameliorated in a variety of animal models by the grafting of fetal neuronal cell
      or tissue into damaged brain. Clinical trials are under way to determine whether
      human fetal mesencephalic tissue can ameliorate motor functions in patients with
      Parkinson's disease. 2. Autopsy findings of parkinsonian patient implanted with
      human fetal mesencephalic tissue clearly revealed that the fetal neuronal graft
      can survive for an extended period of time in the human brain and densely
      reinnervate the surrounding host striatal tissue. 3. It is, however, still
      important to obtain more practical, effective, and ethically justifiable donor
      material for the future clinical application of the procedures. Desirable
      properties for the donor cells include long-term survival in the brain, neuronal
      cell type for the reconstruction of damaged neural circuits, and susceptibility
      to genetic manipulation for the practical use. 4. With the development of
      molecular biology techniques, genetic modification and transplantation of the
      donor neuronal cells might be a feasible way to cure many kinds of central
      nervous system diseases toward a "graft-gene therapy."

PMID- 10079968
TI  - Antibiotics and light responses in superfused bovine retina.
AB  - 1. Our objective was to study effects of clindamycin and ciprofloxacin on the
      electroretinogram (ERG) of isolated bovine retinas. 2. Electroretinograms of
      isolated superfused bovine retinas were recorded under normal conditions and
      during application of clindamycin and ciprofloxacin. The b-wave reduction was
      plotted against the drug concentration. In several cases retinal oxygen uptake
      was also measured. Clindamycin was available only in a preparation containing
      benzyl alcohol. To differentiate between effects caused by the antibiotic and the
      alcohol, ERGs were also recorded under superfusion with benzyl alcohol. To record
      drug effects on photoreceptors synaptic transmission was blocked using 1 mM
      aspartate. 3. At concentrations between 0.3 and 10 mM clindamycin significantly
      reduced the amplitude of the b-wave of the ERG. A comparable reduction of retinal
      oxygen uptake was found at concentrations 10-fold higher. Clindamycin, 3 mM, did
      not affect the a-wave after preincubation with aspartate. Benzyl alcohol at
      concentrations of 0.3 and 1 mM did not affect the b-wave, whereas at higher
      concentrations the b-wave was found to be reduced. Considerable b-wave reductions
      were found with ciprofloxacin at concentrations of between 0.03 and 0.6 mM. All
      effects proved to be fully reversible and dose-dependent. 4. Ciprofloxacin and
      clindamycin did both alter neural function in the isolated superfused bovine
      retina. The nontoxic dosages found here differ considerably from results in
      rabbits after intravitreal injections. This is probably due to species
      differences.

PMID- 10079969
TI  - Biochemical and molecular characteristics of the brain with developing cerebral
      infarction.
AB  - 1. We review the biochemical and molecular changes in brain with developing
      cerebral infarction, based on recent findings in experimental focal cerebral
      ischemia. 2. Occlusion of a cerebral artery produces focal ischemia with a
      gradual decline of blood flow, differentiating a severely ischemic core where
      infarct develops rapidly and an area peripheral to the core where the blood flow
      reduction is moderate (called penumbra). Neuronal injury in the penumbra is
      essentially reversible but only for several hours. The penumbra area tolerates a
      longer duration of ischemia than the core and may be salvageable by
      pharmacological agents such as glutamate antagonists or prompt reperfusion. 3.
      Upon reperfusion, brain cells alter their genomic properties so that protein
      synthesis becomes restricted to a small number of proteins such as stress
      proteins. Induction of the stress response is considered to be a rescue program
      to help to mitigate neuronal injury and to endow the cells with resistance to
      subsequent ischemic stress. The challenge now is to determine how the
      neuroprotection conferred by prior sublethal ischemia is achieved so that
      rational strategies can be developed to detect and manipulate gene expression in
      brain cells vulnerable to ischemia. 4. Expansion of infarction may be caused by
      an apoptotic mechanism. Investigation of apoptosis may also help in designing
      novel molecular strategies to prevent ischemic cell death. 5.
      Ischemia/reperfusion injury is accompanied by inflammatory reactions induced by
      neutrophils and monocytes/macrophages infiltrated and accumulated in ischemic
      areas. When the role of the inflammatory/immune systems in ischemic brain injury
      is revealed, new therapeutic targets and agents will emerge to complement and
      synergize with pharmacological intervention directed against glutamate and Ca2+
      neurotoxicity.

PMID- 10079970
TI  - Alterations of tubulin function caused by chronic antidepressant treatment in rat
      brain.
AB  - 1. Antidepressants have been used clinically for many years; however, the
      neurochemical mechanism for their therapeutic effect has not been clarified yet.
      Recent reports indicate that chronic antidepressant treatment directly affects
      the postsynaptic membrane to increase the coupling between the stimulatory GTP
      binding (G) protein, Gs, and adenylyl cyclase. Tubulin, a cytoskeletal element,
      is involved in the stimulatory and inhibitory regulation of adenylyl cyclase in
      rat cerebral cortex via direct transfer of GTP to G proteins. In this study, we
      investigated whether the functional change of the adenylyl cyclase system caused
      by chronic antidepressant treatment involves an alteration of tubulin function in
      the regulation of adenylyl cyclase activity. 2. Male Sprague-Dawley rats were
      treated once daily with amitriptyline or saline by intraperitoneal injection (10
      mg/kg) for 21 days, and their cerebral cortex membranes and GppNHp-liganded
      tubulin (tubulin-GppNHp) were prepared for what. 3. GppNHp-stimulated adenylyl
      cyclase activity in cortex membranes from amitriptyline-treated rats was
      significantly higher than that in control membranes. Furthermore, tubulin-GppNHp
      prepared from amitriptyline-treated rats was more potent than that from control
      rats in the stimulation of adenylyl cyclase activity in the cortex membranes of
      the controls. However, there was no significant difference in manganese
      stimulated adenylyl cyclase activity between control and amitriptyline-treated
      rats. 4. The present results suggest that chronic antidepressant treatment
      enhances not only the coupling between Gs and the catalytic subunit of adenylyl
      cyclase but also tubulin interaction with Gs in the cerebral cortex of the rat.

PMID- 10079971
TI  - Role of the ryanodine receptor in ischemic brain damage--localized reduction of
      ryanodine receptor binding during ischemia in hippocampus CA1.
AB  - 1. The ryanodine receptor has recently been shown to play a pivotal role in the
      regulation of intracellular Ca2+ concentration via Ca(2+)-induced Ca2+ release
      (CICR). Effects of ischemia on CICR in the brain tissue, however, remain largely
      unknown since only a few reports have been published on this subject. In this
      paper we report on work in this area by our group and review related progress in
      this field. 2. We examined alterations of ryanodine receptor binding and local
      cerebral blood flow (LCBF) at 15 min, 30 min, and 2 hr after occlusion of the
      right common carotid artery in the gerbil brain. A quantitative autoradiographic
      method permitted simultaneous measurement of these parameters in the same brain.
      The LCBF was significantly reduced in most of the cerebral regions on the
      occluded side during each time period of ischemia. In contrast, only in the
      hippocampus CA1 on the occluded side was a significant reduction in ryanodine
      binding found at 15 min, 30 min and 2 hr after the occlusion. 3. These findings
      suggest that suppression of ryanodine binding in the hippocampus CA1 may be
      attributable to a regionally specific perturbation of CICR and that this
      perturbation may be closely associated with the pathophysiological mechanism that
      leads to be selective ischemic vulnerability of this region. 4. Other recent
      studies have also reported an important role for ryanodine receptors in neuronal
      injury such as the delayed neuronal death in the hippocampus CA1. These data
      suggest that derangement of CICR is likely to be involved in acute neuronal
      necrosis as well as in delayed neuronal death in ischemia. 5. Further studies on
      clarifying the role of CICR in ischemic brain damage are needed in order to
      develop new therapeutic strategies for stroke patients.

PMID- 10079972
TI  - Oxidative resistance of Na/K-ATPase.
AB  - 1. Oxidative modification of Na/K-ATPase from brain and kidney has been studied.
      Brain enzyme has been found to be more sensitive than kidney enzyme to inhibition
      by both H2O2 and NaOCl. 2. The inhibition of Na/K-ATPase correlates well with the
      decrease in a number of SH groups, suggesting that the latter belong mainly to
      ATPase protein and are essential for the enzyme activity. We suggest that the
      differences in the number, location, and accessibility of SH groups in Na/K
      ATPase isozymes predict their oxidative stability. 3. The hydrophilic natural
      antioxidant carnosine, the hydrophobic natural antioxidant alpha-tocopherol, and
      the synthetic antioxidant ionol as well as the ferrous ion chelating agent
      deferoxamine were found to protect Na/K-ATPase from oxidation by different
      concentrations of H2O2. The data suggest that these antioxidants are effective
      due to their ability to neutralize or to prevent formation of hydroxyl radicals.

PMID- 10079973
TI  - Na/K-ATPase under oxidative stress: molecular mechanisms of injury.
AB  - 1. The authors compare oxidative injury to brain and kidney Na/K-ATPase using in
      vitro and in vivo approaches. The substrate dependence of dog kidney Na/K-ATPase
      was examined both before and after partial hydrogen peroxide modification. A
      computer simulation model was used for calculating kinetic parameters. 2. The
      substrate dependence curve for the unmodified endogenous enzyme displayed a
      typical curve with an intermediate plateau, adequately described by the sum of
      hyperbolic and sigmoidal components. 3. The modified enzyme demonstrated a
      dependent curve that closely approximates normal hyperbola. The estimated ATP
      K(m) value for the endogenous enzyme was about 85 microM; the Kh was equal to 800
      microM. The maximal number of protomers interacting was 8. Following oxidative
      modification, the enzyme substrate dependence curve did not show a significant
      change in the maximal protomer rate Vm, while the K(m) was increased slightly and
      interprotomer interaction was abolished. 4. Na/K-ATPase from an ischemic gerbil
      brain showed a 22% decrease in specific activity. The maximal rate of ATP
      hydrolysis by an enzyme protomer changed slightly. but the sigmoidal component,
      characterizing the enzyme's ability to form oligomers was abolished completely.
      The K(m) value was almost unchanged, but the Hill coefficient fell to 1. These
      data show that Na/K-ATPase molecules isolated from the ischemic brain have lost
      the ability to interact with one another. 5. We suggest that the most important
      consequence of oxidative modification is Na/K-ATPase oligomeric structure
      formation and subsequent hydrolysis rate suppression.

PMID- 10079974
TI  - Reoxygenation injury of human brain capillary endothelial cells.
AB  - 1. Many studies have demonstrated that endothelial cells from several species can
      generate oxygen free radicals when subjected to anoxia and reoxygenation.
      However, due to the heterogeneity of the endothelium within different organs and
      species, the effects of superoxide dismutase (SOD), catalase, and allopurinol on
      reoxygenated cultured cells remain quite controversial. 2. This review outlines
      the possible sources of oxygen free radicals within brain endothelial cells. 3.
      We examine the aspects of the effects of SOD catalase and allopurinol on cultured
      human brain capillary endothelial cells upon reoxygenation. 4. Also, we introduce
      briefly a method of culturing human brain capillary endothelial cells and present
      our experimental results on the effects of SOD, catalase, and allopurinol in
      these cultured cells following anoxia and reoxygenation.

PMID- 10079975
TI  - Metabolic transformation of neuropeptide carnosine modifies its biological
      activity.
AB  - 1. The ability of carnosine and carnosine-related compounds (CRCs) to interact
      with several free oxygen radicals is analyzed. 2. Carnosine, the CRCs (imidazole,
      histidine, anserine), and ergothioneine were found to be equally efficient in
      singlet oxygen quenching. During generation of hydroxyl radicals from hydrogen
      peroxide in the Fenton reaction, carnosine was found to be more effective than
      the CRCs tested. 3. By measuring the chemiluminescence produced by carnosine and
      CRCs in rabbit leukocytes in the presence of luminol or lucigenin, we conclude
      that carnosine and other CRCs play a stimulating role in superoxide oxygen
      production while suppressing the myeloperoxidase system. 4. ADP-induced
      aggregation of human platelets is slightly stimulated by carnosine but is
      inhibited by acetylanserine. 5. The following rank order of efficiency of CRCs
      was demonstrated while measuring the oxidation of human serum lipoproteins:
      acetylcarnosine < acetylanserine < homocarnosine = ophidine < carnosine <
      anserine. 6. The results obtained demonstrate that metabolic transformation of
      carnosine into CRCs in tissues may play an important role in regulating the
      native antioxidant status of the organism.

PMID- 10079977
TI  - Recognition of the immunocompromised patient.
AB  - The host defense systems in humans are highly specialized with respect to
      categories of infectious pathogens; yet, there is just enough overlap to protect
      one from minor defects. It is also important to appreciate that not all
      abnormalities reported from the laboratory are clinically significant. By
      appreciating the clinical syndromes that accompany various deficiencies, the
      surgeon can be aware of the at-risk patient.

PMID- 10079976
TI  - Role of nitric oxide in pathogenesis underlying ischemic cerebral damage.
AB  - 1. Based upon the intriguing report that nitric oxide synthase (NOS) inhibitor
      dose-dependently reverses N-methyl-D-aspartate (NMDA)-induced neurotoxicity
      observed in primary cortical cell cultures, many laboratories have investigated
      whether NOS inhibition is beneficial as a treatment for cerebral ischemia. 2.
      Although the results are variable, it is likely thought that nitric oxide plays a
      key role in pathomechanism underlying ischemic brain damage. 3. We review the
      experimental studies on effects of NOS inhibition on cerebral ischemia and
      measuring nitric oxide produced in the brain subjected to cerebral ischemia. 4.
      Finally, the possibility of NOS inhibitors as a therapeutical tool is discussed.

PMID- 10079978
TI  - The initial pulmonary evaluation of the immunocompromised patient.
AB  - Practical approaches to the initial evaluation of solid organ transplant
      patients, BMT patients, and HIV-infected patients with pulmonary disease are
      summarized in Figures 2, 3, and 4. These algorithms are meant to be used as
      guidelines for the clinician. The clinical setting will ultimately determine the
      extent and speed of the evaluation. Patients who are recipients of solid organ
      transplants and have pulmonary symptoms may have focal or diffuse changes or may
      have normal chest radiographs. In all these groups, sputum is obtained by
      expectation. If a pathogen is found in any of the groups, it is treated. When no
      pathogen is found on sputum examination in patients with focal disease, empiric
      antibiotic therapy is given. If the patients do not improve on the empiric
      antibiotics, then bronchoscopy is performed. Some centers proceed directly to
      bronchoscopy before antibiotics are started in the hope of directing antibiotic
      therapy. Patients who have a normal CXR or diffuse infiltrates and no identified
      pathogen on examination of sputum undergo bronchoscopy, and the protocol is
      followed until a diagnosis is made (see Fig. 2). Patients who have received a BMT
      and who present with pulmonary symptoms are treated as shown in Figure 3. The CXR
      will reveal if the infiltrate is focal or diffuse. Those with focal infiltrates
      are treated with broad-spectrum antibiotics for 48 to 72 hours. If the symptoms
      and signs do not show some resolution, then bronchoscopy is usually performed.
      The effect of diffuse infiltrates in BMT patients depends to a large extent how
      far along in recovery from the transplant the patient is when they develop the
      infiltrates. During the first 30 days posttransplant, pulmonary edema commonly
      occurs, and the infiltrates may resolve with diuresis. If the patient is not
      clinically fluid overloaded or they do not respond to the diuretic therapy, then
      bronchoscopy with BAL is indicated. Finally, many HIV-infected patients may
      present with pulmonary symptoms. They may have a normal CXR or a diffuse or focal
      pattern (Fig. 4). All patients are subjected to sputum induction to identify a
      pathogen. If one is identified, it is treated. Should the patient not respond to
      treatment adequately or a pulmonary pathogen is not found, then bronchoscopy with
      BAL, protected specimen brush, or a transbronchial biopsy is attempted. The above
      schema is a general guideline to the initial evaluation of pulmonary disorders in
      the ICP. The respiratory abnormality is found in most of the cases if these
      algorithms are closely followed. If the patient does not improve or deteriorates
      further, additional diagnostic procedures such as video-assisted thorascopic lung
      biopsy or CT-directed transthoracic needle biopsy may be needed.

PMID- 10079979
TI  - New directions in antimicrobial therapy.
AB  - The virulent microorganisms that we try to contain with new antimicrobial agents
      quickly find the gap in our defenses and exploit it. Resistance to all available
      antibiotics at the same time, however, rarely occurs. The authors report the most
      current antimicrobials used as monotherapy or in combination to successfully
      treat the more resistant pathogens. The higher mortality and subsequent cost to
      treat these infections are reviewed.

PMID- 10079980
TI  - Malignancies associated with the immunocompromised state.
AB  - Neoplastic disease occurs more frequently in immunocompromised patients than in
      the general population. These tumors occur at an earlier age and behave more
      aggressively. Their origin is linked to viral infection and other causes of
      immunodeficiency, such as antirejection drugs. Despite aggressive therapy, these
      patients have a poor prognosis when compared with immunocompetent individuals
      with similar tumors.

PMID- 10079981
TI  - Complications from induction regimens for thoracic malignancies. Perioperative
      considerations.
AB  - The treatment of locoregionally advanced non-small cell lung cancer is evolving
      rapidly, and we as surgeons should continue to take a prominent role, from the
      pretreatment evaluation phase, through reassessment after induction therapy and
      intraoperative decision making, to vigilant postoperative care. These are by far
      the most challenging thoracic oncologic patients to care for. The
      multidisciplinary team formula required for optimal results and mandates the
      leadership that we, as surgeons familiar with all facets of patient care, can
      provide.

PMID- 10079982
TI  - The thoracic surgeon's role in the management of patients with HIV infection and
      AIDS.
AB  - The advent of improved medical therapy with multidrug HIV medicines including
      protease inhibitors has prolonged life expectation of patients with HIV
      infection. The risk of perinatal transmission has also decreased with education
      and antiviral medications. Education of all groups about precautions to decrease
      HIV transmission appears to have resulted in a decline in the disease incidence;
      however, this trend has not been mirrored in other countries. All of these
      factors combine to increase the probability that the surgeon's role to take care
      of patients with HIV-related illnesses could be significant in the future. The
      thoracic surgeon may be called upon to assist in the diagnosis and treatment of
      HIV-infected patients with thoracic complications including pulmonary, cardiac,
      and esophageal problems. The morbidity and mortality of procedures performed on
      these patients appear to be no different than patients without HIV. We use very
      aggressive treatment strategies in patients with AIDS and HIV infections. The use
      of VATS, especially in the treatment of pneumothoraces and empyemas, should be
      used and has been shown to be safe and efficacious.

PMID- 10079983
TI  - Noninfectious immunologic disorders in adults.
AB  - This article covers a variety of immunologic defects and discusses their
      potential side effects, with an emphasis on immunodeficiencies with survival into
      adulthood. To organize the approach to immunodeficiencies, the immune system is
      broken down broadly into four major components: the complement cascade, antibody
      (B cell)-mediated immunity, cellular (T cell)-mediated immunity, and
      phagocytosis.

PMID- 10079984
TI  - Thoracic complications in solid organ transplantation.
AB  - Thoracic complications of solid organ transplantation are common and can arise
      from the implantation surgical procedure or can be secondary to the need for
      lifelong immunosuppression. Problems that arise can be general to cardiothoracic
      surgery or unique to transplant patients. This article provides an overview of
      these complications and some approaches to their avoidance and management.

PMID- 10079985
TI  - Thoracic complications related to bone marrow transplantation.
AB  - Although progress has been made in the diagnosis and management of respiratory
      complications after BMT, such complications are still frequent and are a major
      cause of morbidity and mortality. The use of CMV-negative marrow and blood
      products, surveillance bronchoscopies, and prophylactic use of antivirals have
      significantly reduced the incidence of CMV pneumonia. DNA amplification
      techniques have allowed earlier detection of viral respiratory infections, and
      early detection of localized invasive aspergillosis can improve survival with
      lung resection and antifungal therapy. Finally, consideration for open lung
      biopsy should include the patient's degree of preoperative respiratory
      impairment, because this may relate to early postoperative survival.

PMID- 10079986
TI  - Opportunistic thoracic infections. Bacteria, viruses, and protozoa.
AB  - The range of potential bacterial, viral, and protozoan pathogens that can cause
      pulmonary infections in immunocompromised patients is extensive. An aggressive
      diagnostic approach is essential to maximizing chances for a successful outcome.
      This article discusses the general diagnostic approach and provides a discussion
      of the most important bacterial, viral, and protozoan chest infections occurring
      in this setting.

PMID- 10079987
TI  - Aspergillus and other fungi.
AB  - Opportunistic infections that arise in the immunocompromised host are a major
      cause of morbidity and mortality. Although bacterial infections are more
      frequent, invasive fungal infections occur commonly and carry higher risks in
      these immunocompromised patients. Newer antifungal agents, along with an
      occasional pulmonary resection, have improved the treatment options and the
      survival from invasive fungal infections in immunocompromised patients.

PMID- 10079988
TI  - Mycobacterium tuberculosis and other mycobacteria.
AB  - The immunocompromised post-transplant HIV-positive patient is at increased risk
      for mycobacterial infection. Early diagnosis and aggressive therapy is critical
      to successful outcome. Surgical therapy may be required in patients who have
      complex mycobacterial lung disease, drug resistant tuberculosis, or mycobacterial
      infections other than tuberculosis.

PMID- 10079989
TI  - Congenital immunodeficiency syndromes.
AB  - Cogenital abnormalities of innate or acquired immunity, although not common,
      produce multiple problems for which the surgeon may be consulted. Even if the
      diagnosis has not been previously made, patients with abnormal situs, congenital
      heart disease, failure to heal surgical wounds, pneumatoceles,
      lymphoproliferative disorders, recurrent severe infections, or autoimmune
      destruction of formed elements of the blood may have one of the disorders
      discussed above.

PMID- 10079990
TI  - Sternal acceleration ballistocardiography and arterial pressure wave analysis to
      determine stroke volume.
AB  - OBJECTIVE: To describe a cardiac output measurement using a new method to derive
      and analyze the long-axis ballistocardiogram that is less invasive than pulmonary
      artery thermodilution. DESIGN: Prospective physiologic study. SETTING: Intensive
      care unit of The Halifax Infirmary, a teaching hospital of Dalhousie University,
      Halifax, NS. PATIENTS: Thirty-nine patients in sinus rhythm with pulmonary artery
      thermodilution catheters or radial artery catheters in place. The first 30
      subjects were the "learning set" and the next 9 were the "test set."
      INTERVENTIONS: A small (54-g) accelerometer was taped on the patient's chest.
      OUTCOME MEASURES: Measurements of time and amplitude coordinates of the
      acceleration and radial artery pressure wavepeaks, as well as anthropometric
      information. RESULTS: A stroke volume prediction equation was generated (R2 =
      0.76) from the learning set. This equation was applied to the test set and
      correlated with the pulmonary artery thermodilution-derived stroke volumes (R =
      0.79). Stroke volumes were compared using a previously described statistical
      method: a) bias (predicted > thermodilution) = 0.03 mL (95% confidence interval
      [CI] -4.2 to 4.8 mL); b) lower limit of agreement = -21 mL (95% CI -29 to -13
      mL); c) upper limit of agreement = 22 mL (95% CI 14 to 29 mL). Of derived stroke
      volumes, 82% were within 15 mL of pulmonary artery thermodilution-derived values.
      CONCLUSIONS: The sternal acceleration ballistocardiogram combined with
      hemodynamic and demographic data in a probabilistic model shows promise of
      providing a less invasive measure of cardiac output than thermodilution.

PMID- 10079991
TI  - The challenge for basic science education in problem-based medical curricula.
AB  - There has been intense debate about medical curriculum reform since the early
      1950s. The last 25 years have seen a steady shift ward problem-based learning
      curriculum design in schools of medicine and allied health sciences. This trend
      has been less challenging for clinical departments than for departments of basic
      science, where it has often evoked anxiety, antipathy, lack of cooperation, and
      general mistrust. This appears paradoxical, as problem-based learning (PBL) is
      promoted as an improved method of integrating scientific concepts, and the
      advances that drive much of modern medical practice are advances in the basic
      sciences. While proponents of PBL argue that the approach promotes better
      integration and use of scientific concepts, the evidence, such as it is, is
      against this. As well, other evidence suggests that clinicians do not use basic
      science concepts extensively in their practice. This then questions the utility
      of scientific knowledge in a medical curriculum. This article examines this
      notion of utility (the quality or state of being useful), to establish some
      ground rules for what does, and does not, possess utility, and to present
      strategies to develop specific objectives from general statements concerning
      utility. Understanding of biologic and pathologic processes becomes of central
      importance and arguably possesses utility. If it is both required and evaluated,
      such understanding necessitates mastery of basic science concepts. Previously,
      the presentation of the basic sciences in medical curricula has emphasized the
      acquisition of knowledge rather than its use. Such learning has been perceived to
      lack utility; strategies to enhance the value of studying basic science concepts
      are suggested. If the importance of objectives in the basic medical sciences is
      accepted, these objectives should be achieved early in training, maintained at
      exit from medical school, and revisited in continuing medical education. The
      process of change in medical education initiated by Abraham Flexner early in this
      century remains incomplete. One reason why curricular changes have proved
      frustrating to basic scientists is that much of clinical medicine remains
      unnecessarily unscientific. Until clinical medicine itself changes, the utility
      of science in the training of a physician will remain difficult to demonstrate.

PMID- 10079992
TI  - Basic science in medical education.

PMID- 10079993
TI  - 12th annual North American Cystic Fibrosis Conference. October 15-18, 1998,
      Montreal, Canada.

PMID- 10079994
TI  - Biography of Peter J. Janetta, M.D., D.Sci.

PMID- 10079995
TI  - Bibliography of Peter J. Jannetta, M.D., D.Sci.

PMID- 10079996
TI  - Presidential address: "how do you know?".

PMID- 10079997
TI  - In vitro neurogenesis by adult human epileptic temporal neocortex.

PMID- 10079998
TI  - Selection criteria for degenerative lumbar spine instability.

PMID- 10079999
TI  - Evidence-based management of type II odontoid fractures.

PMID- 10080000
TI  - Criteria for patient selection: low-grade gliomas.

PMID- 10080001
TI  - Selection of patients for surgery for Parkinson's disease.

PMID- 10080002
TI  - Selection criteria for the treatment of cranial rhizopathies by microvascular
      decompression (honored guest lecture).

PMID- 10080003
TI  - Temporal lobe epilepsy.

PMID- 10080004
TI  - Indications for carotid endarterectomy.

PMID- 10080005
TI  - Degenerative lumbar spinal instability: technical aspects of operative treatment.

PMID- 10080006
TI  - Surgical techniques for upper cervical spine decompression and stabilization.

PMID- 10080007
TI  - Surgery of low-grade gliomas--technical aspects.

PMID- 10080008
TI  - Operative techniques and clinicopathologic correlation in the surgical treatment
      of cranial rhizopathies (honored guest lecture).

PMID- 10080009
TI  - Posterior ventral pallidotomy: techniques and theoretical considerations.
AB  - 1. Microeletrode mapping of the pallidum and adjacent structures allows for
      precise target identification and localization of critical structures, i.e.,
      optic tract, internal capsule, and external pallidum, which must be spared from
      lesioning. 2. Microelectrode mapping has provided physiologic-anatomic
      correlation of determining the optimal target location as related to clinical
      outcome and has helped to refine the role of stimulation as a tool for target
      localization. 3. The improved accuracy of this technique should result in more
      accurate lesion placement which should improve long-term outcome and decrease
      morbidity.

PMID- 10080010
TI  - Surgical techniques in temporal lobe epilepsy.

PMID- 10080011
TI  - Carotid endarterectomy: how the operation is done.

PMID- 10080012
TI  - Monitoring in traumatic brain injury.
AB  - In the past several years, improvements in technology have advanced the
      monitoring capabilities for patients with TBI. The primary goal of monitoring the
      patient with TBI is to prevent secondary insults to the brain, primarily cerebral
      ischemia. Cerebral ischemia may occur early and without clinical correlation and
      portends a poor outcome. Measurement of ICP is the cornerstone of monitoring in
      the patient with TBI. Monitoring of ICP provides a measurement of CPP and a rough
      estimation of CBF. However, with alterations in pressure autoregulation,
      measurement of CPP does not always allow for determination of CBF. To circumvent
      this problem, direct measurements of CBF can be performed using clearance
      techniques (133Xe, N2O, Xe-CT) or invasive monitoring techniques (LDF, TDF,
      NIRS). Although direct and quantitative, clearance techniques do not allow for
      continuous monitoring. Invasive CBF monitoring techniques are new, and
      artifactual results can be problematic. The techniques of jugular venous
      saturation monitoring and TCD are well established and are powerful adjuncts to
      ICP monitoring. They allow the clinician to monitor cerebral oxygen extraction
      and blood flow velocity, respectively, for any given CPP. Use of TCD may predict
      posttraumatic vasospasm before clinical sequelae. Jugular venous saturation
      monitoring may detect clinically occult episodes of cerebral ischemia and
      increased oxygen extraction. Jugular venous saturation monitoring optimizes the
      use of hyperventilation in the treatment of intracranial hypertension. Although
      PET and SPECT scanning allow direct measurement of CMRO2, these techniques have
      limited application currently. Similarly, microdialysis is in its infancy but has
      demonstrated great promise for metabolic monitoring. EEG and SEP are excellent
      adjuncts to the monitoring arsenal and provide immediate information on current
      brain function. With improvements in electronic telemetry, functional monitoring
      by EEG or SEP may become an important part of routine monitoring in TBI.

PMID- 10080013
TI  - Outcome analysis in lumbar spine: instabilities/degenerative disease.
AB  - In summary, expectations for outcome analysis have changed over the last several
      years. It is no longer the case that outcome analysis is expected to be done by
      academic institutions alone. Surgeons in private practice are rapidly approaching
      the time when outcome analysis of personal results will be necessary for
      competitive marketing purposes. In addition, the definition of outcome analysis
      has been considerably expanded from medical outcome to include functional
      outcome, return to work, quality of life, patient satisfaction, and cost
      effectiveness. The above discussion has considered several aspects of data
      outcome analysis for degenerative disease of the lumbar spine. It is the intent
      of this review to help surgeons prepare themselves for changing expectations in
      their new medical environment.

PMID- 10080014
TI  - Upper cervical spine trauma: outcome assessment.

PMID- 10080015
TI  - Low-grade gliomas: in search of evidence-based treatment.

PMID- 10080016
TI  - Outcome after microvascular decompression for typical trigeminal neuralgia,
      hemifacial spasm, tinnitus, disabling positional vertigo, and glossopharyngeal
      neuralgia (honored guest lecture).

PMID- 10080017
TI  - Outcomes assessment for pallidotomy.

PMID- 10080018
TI  - Analysis of outcome: temporal lobe resection.

PMID- 10080019
TI  - Analysis of outcome in carotid endarterectomy trials.
AB  - The trials for carotid endarterectomy have had a major impact on the practice of
      medicine. Beyond demonstrating the efficacy of this procedure for stroke
      prevention in certain patient cohorts, these studies have set a standard for the
      evaluation of surgical procedures by carefully planned, scientifically rigorous,
      prospective randomized controlled trials. In addition, data from these trials
      have been used to develop clinical guidelines (2, 12, 24), determine
      reimbursement policies, and establish criteria for perioperative morbidity.
      Concordance of methodology (especially primary outcome measures) among the
      various trials has enabled important valid comparisons between different patient
      cohorts. The benefit provided by carotid endarterectomy in most trials was so
      profound that the relative imprecision of stroke-related outcome measures did not
      significantly affect the findings. New outcome measures for stroke that evolved
      during these studies are being applied to ongoing trials for a variety of stroke
      therapies.

PMID- 10080020
TI  - Outcomes analysis: intracranial pressure monitoring.

PMID- 10080021
TI  - Tentorial meningiomas.

PMID- 10080022
TI  - Foramen magnum meningiomas.

PMID- 10080023
TI  - Cranial base chordomas.

PMID- 10080024
TI  - Epidermoid and dermoid cysts of the posterior fossa.

PMID- 10080025
TI  - Vestibular neurilemmomas (honored guest lecture).

PMID- 10080026
TI  - Brainstem gliomas.

PMID- 10080027
TI  - Ependymomas.

PMID- 10080028
TI  - Medulloblastoma.

PMID- 10080029
TI  - [Dissociation of the catalytic and binding subunits of viscumin occurs before
      translocation of the toxin across the membrane].

PMID- 10080030
TI  - [Nucleotide level evaluation of the genetic variability of the human population
      in ecologically unfavorable regions of the Techa river].

PMID- 10080031
TI  - [Detection of an extended protein-binding domain in the ct6-enhancer region of
      the drosophila cut locus].

PMID- 10080032
TI  - [Effect of opioid peptides from food origins on the cardiotropic components of
      stress].

PMID- 10080033
TI  - [Determination of the effect of long-term maintenance of the radiation adaptive
      response in murine bone marrow].

PMID- 10080034
TI  - [Transduction of the plasmid pBR322 antibiotic-resistance determinant by pseudo-T
      even bacteriophages].

PMID- 10080035
TI  - A new editor looks to the past and future of Drug and Alcohol Dependence.

PMID- 10080036
TI  - Effect of gonadectomy on discriminative stimulus effects of morphine in female
      versus male rats.
AB  - In a previous study, we found sex differences in the potency of morphine as a
      discriminative stimulus; the present study was designed to determine whether sex
      differences in gonadal hormones contribute to sex differences in morphine's
      discriminative effects. Adult female and male rats were gonadectomized (GNDZ) or
      sham-gonadectomized (SHAM), and then trained to discriminate 3.0 mg/kg morphine
      from saline. The ED50 for morphine discrimination was significantly lower in
      females than in males (0.66 +/- 0.12 vs. 1.25 +/- 0.16 mg/kg, respectively); ED50
      values in GNDZ rats were slightly higher than in SHAM rats. The time course of
      morphine discrimination was not significantly different in females and males,
      whether GNDZ or not. The micro agonist fentanyl completely substituted for
      morphine in all rats, with no group differences in ED50 value. The micro agonists
      buprenorphine and nalbuphine substituted for morphine in nearly all females and
      in all SHAM males, but in only four of seven GNDZ males. The kappa agonist
      U69,593 did not substitute for morphine in rats of any group. Most opioid
      agonists were significantly more potent in decreasing response rate in males than
      females, and in GNDZ than SHAM rats; morphine and nalbuphine also increased
      response rate above control in some females. A pA2 analysis of naltrexone in
      combination with morphine suggested that there were no significant differences
      among groups in receptors at which morphine produced its discriminative stimulus
      effects. Although hormone replacement in GNDZ female rats at the end of the study
      reinstated estrous cycling, it did not substantially alter the ED50 for morphine
      discrimination. Thus, sex differences in potency of morphine as a discriminative
      stimulus may not be due to sex differences in gonadal hormone milieu. The
      possibility that sex differences in reinforcement frequency on morphine versus
      saline levers caused the sex differences in morphine discrimination is discussed.

PMID- 10080037
TI  - Pharmacological effects of methamphetamine and other stimulants via inhalation
      exposure.
AB  - The effects of methamphetamine-HCl, methcathinone-HCl, cocaine and ephedrine on
      locomotor stimulation were compared between inhalation exposure and i.v.
      injection in mice. Methamphetamine-HCl was readily volatilized upon heating at
      300 degrees C in a glass pipe with only trace amounts of amphetamine being
      produced. The ED50 dose (9.4 and 6.5 mumol/kg for inhalation exposure and i.v.
      injections, respectively) and biodisposition of methamphetamine-HCl were similar
      for both routes of administration. Methcathinone-HCl and cocaine were readily
      volatilized. Their dose response profiles also appeared similar for both routes
      of administration. Ephedrine did not appear to be easily volatilized and was only
      effective in stimulating locomotor activity after i.v. administration. These
      findings indicate that inhalation exposure to methamphetamine-HCl, cocaine and
      methcathinone possess similar pharmacological characteristics as the i.v. route
      of administration. In particular, this model may have implications in predicting
      the pharmacological activity of various stimulants via the inhalation route of
      administration.

PMID- 10080038
TI  - Ecstasy (MDMA) dependence.
AB  - Methylenedioxymethamphetamine (MDMA) is generally described as non-addictive.
      However, this report describes three cases in which criteria for dependence were
      met. A wider understanding that MDMA can be addictive in rare cases is important
      as very heavy use may cause lasting neuronal changes. This risk could be reduced
      with effective identification and treatment of dependent persons. In one case
      dependence was linked with self-medication of post-traumatic stress disorder
      (PTSD).

PMID- 10080039
TI  - Measuring interstate variations in drug problems.
AB  - This article describes the Drug Problem Index (DPI), a composite index measuring
      the interstate severity of drug abuse problems. The DPI's components (drug-coded
      mortality, drug-defined arrest, and drug-treatment client rates) were selected
      because they were linked closely with drug abuse, data were available for all
      states, and there was published evidence of their validity. The variables were
      reliable, and their convergent validity was estimated in a multi-trait, multi
      method matrix. We found evidence consistent with the DPI's construct validity in
      its relations with other consequences of drug abuse. The DPI correlated
      significantly with the Block Grant drug need index but not with model estimates
      of drug dependence based on the National Household Survey.

PMID- 10080040
TI  - Gender, injury status and acculturation differences in performance of screening
      instruments for alcohol problems among US Hispanic emergency department patients.
AB  - The sensitivity and specificity of several screening instruments including the
      CAGE, brief MAST, AUDIT, TWEAK, RAPS, and Trauma Scale, were evaluated against
      both ICD-10 and DSM-IV criteria for alcohol dependence and for harmful drinking
      and abuse in a probability sample of 586 Hispanic emergency department patients.
      Screening instruments were not as sensitive for females as for males, for those
      in the low acculturation group, or for non-dependent drinkers. Acculturation was
      positively associated with the likelihood of being a current drinker and among
      current drinkers, was positively associated with alcohol dependence and with
      harmful drinking or alcohol abuse.

PMID- 10080041
TI  - Nicodermal patch adherence and its correlates.
AB  - The patch adherence behavior of 101 smokers receiving 8 weeks of the nicodermal
      patch was examined while undergoing one of three levels of adjunctive
      psychosocial treatment. Additionally, regression analyses were undertaken to: (1)
      identify subject variables predictive of patch adherence and (2) to determine the
      predictive validity of patch treatment dropout, smoking and patch adherence
      during patch treatment to smoking 9 and 26 weeks post-treatment entry. Fifty-five
      percent of the patients wore the patch as prescribed for at least 50 of 56
      treatment days. A multiple regression model including the Fagerstrom severity of
      dependence score, psychosocial treatment group, and the URICA commitment score
      predicted 18% of the variance in days of patch use. All treatment dropouts were
      found to be smoking at followup. Although both smoking and low patch compliance
      during treatment were significant predictors subjects of week 9 and 26 smoking
      for the remaining subjects, at the individual variable level of analysis, only
      smoking during treatment predicted week 9 and 26 outcomes in a two-variable
      predictor model.

PMID- 10080042
TI  - An innovative approach to reducing cannabis use in a subset of methadone
      maintenance clients.
AB  - Cannabis use rates among methadone maintenance clients are high. We attempted to
      decrease cannabis use in our most stable clients by adding a requirement to the
      take home dose policy that clients provide cannabis free urines to achieve twice
      a week pick up status (2 x /week). The urine records and take home status of all
      clients were monitored for the 6 months prior to implementation of the policy
      change and 1 year following. A total of four of eight clients (50%) on 2 x /week
      status who were using cannabis discontinued their use in order to maintain 2 x
      /week status or to return to 2 x /week status if it had been lost.

PMID- 10080043
TI  - Antisocial behavioral syndromes among residential drug abuse treatment clients.
AB  - We compared residential addictions treatment clients meeting full criteria for
      antisocial personality disorder (ASPD+) with those reporting syndromal levels of
      antisocial behavior only in adulthood (AABS+) on demographics, antisocial
      symptomatology, drug history, axis I comorbidity and characteristics of index
      treatment episode. We examined these issues in the sample as a whole, as well as
      separately in male and female respondents. Among both men and women, ASPD+
      initiated their antisocial behavior earlier, met more ASPD criteria and endorsed
      more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime
      axis I diagnoses and reported more years of drug involvement than male AABS+.
      Trends were observed toward poorer retention in treatment among ASPD+ than among
      AABS+ participants of both genders randomized to a planned duration of 180 days,
      but retention did not differ between ASPD+ and AABS+ randomized to a planned
      duration of 90 days. Our findings, which replicate and extend previously
      published results, carry potential implications for treatment programming and for
      the nosology of ASPD.

PMID- 10080044
TI  - Continued heroin use during methadone treatment: relationships between frequency
      of use and reasons reported for heroin use.
AB  - Seventy-seven (71%) of a group of 109 attenders at an out-patient drug treatment
      service reported that they had used heroin in the 90 days before interview, of
      whom 24 (31%) had used every day. Daily users were more likely to explain their
      use in terms of needing to curb withdrawals than were occasional heroin users.
      The latter group were more likely to report availability as a reason for use.
      From a clinical perspective, it is likely that those who use opportunistically
      are less likely to change their use as a function of clinical responses (e.g.
      higher methadone dose) than are those whose use is motivated by the attempt to
      curb withdrawal symptoms.

PMID- 10080045
TI  - Non-injection substance use correlates with risky sex among men having sex with
      men: data from HIVNET.
AB  - Associations between substance use and sexual behavior were examined among 3220
      seronegative men who have sex with men (MSM) in a HIV vaccine preparedness study.
      Relationships between current and past substance use and current sexual risk were
      evaluated using crude odds ratios and logistic regression to adjust for
      confounding variables. Heroin and injection drug use were uncommon (< 2%).
      Substances most often used were alcohol (89%), marijuana (49%), nitrite inhalants
      (29%), amphetamines or similarly acting stimulants (21%), cocaine 14% and
      hallucinogens (14%). Increased adjusted odds for unprotected sex were
      significantly associated with current heavy alcohol use (OR 1.66; CI 1.18, 2.33),
      past alcohol problems (OR 1.25; CI 1.05, 1.48), and current drug use (OR 1.26; CI
      1.08, 1.48). When associations with specific drugs and nitrite inhalants were
      examined separately, current use of cocaine and other stimulants (OR 1.25; CI
      1.01, 1.55), hallucinogens (OR 1.40; CI 1.10, 1.77), and nitrite inhalants (some
      (OR 1.61; CI 1.35, 1.92); heavy (OR 2.18; CI 1.48, 3.20)), were independently
      associated with unprotected sex. Those with past drug use or past heavy alcohol
      use but not currently using demonstrated no increase in sexual risk, suggesting
      an important role for substance-focused interventions in risk reduction efforts
      among MSM.

PMID- 10080046
TI  - Evaluation of the intravenous reinforcing effects of clonidine in baboons.
AB  - Clonidine HCl is an antihypertensive that is also sometimes used to alleviate
      symptoms of withdrawal during narcotics detoxification. Recently, there have been
      reports abuse of clonidine by methadone patients and opioid abusers. The present
      study evaluated the intravenous self-administration of clonidine in four baboons.
      Self-injections were available 24 h/day under a fixed-ratio (FR 120 or 160)
      schedule of injection with a 3-h timeout after each injection. Doses of clonidine
      (0.0001-0.056 mg/kg per injection) or its vehicle (saline) were substituted for
      cocaine (0.32 mg/kg) for at least 15 days. Food pellets were available
      continuously under a concurrent FR 30 schedule of pellet delivery. Clonidine
      maintained self-injection greater than its saline vehicle in all four baboons.
      Although self-injection of clonidine increased as a function of dose within each
      baboon, there were differences between baboons in the range of doses of clonidine
      that maintained self-injection. Doses of 0.032 or 0.056 mg/kg maintained peak
      mean levels of clonidine self-injection which ranged from low (3.2
      injections/day) to high (> 6 injections/day) across baboons. Levels of self
      injection were similar to vehicle at 0.01 mg/kg clonidine in two of four baboons.
      However, in the other two baboons, very low doses of clonidine (0.0001-0.001
      mg/kg) maintained low to moderate levels of self-injection. Acute administration
      of clonidine produced signs of sedation including lip droop, drooling and sitting
      with eyes closed. At high doses, some toxicity was apparent: Baboons were pale
      and not responsive. Food intake was generally increased in a dose dependent
      manner. The present study indicates that clonidine functions as a positive
      reinforcer.

PMID- 10080047
TI  - Dependence symptoms but no diagnosis: diagnostic 'orphans' in a 1992 national
      sample.
AB  - The alcohol dependence syndrome was initially presented as a condition with
      graded severity. However, to receive a diagnosis that is categorical, a
      diagnostic threshold must be determined. Much previous research on this issue has
      focused on setting a threshold that will produce the highest possible consistency
      in rates between one set of diagnostic criteria and the next. It is possible that
      a different threshold may be more valid. Results from a community sample
      supported a minimum diagnostic threshold of three or more dependence symptoms but
      the sample was not nationally representative. Therefore, we investigated the
      meaning of the 'orphan' status (one or two dependence symptoms but no DSM-IV
      alcohol dependence diagnosis) in a large national sample. Two sets of analyses
      were performed, the first using a current timeframe and the second using a
      lifetime timeframe. Abstainers were excluded from all analyses. In each set of
      analyses, three groups were compared: subjects with no symptoms of any alcohol
      use disorder; diagnostic 'orphans' with one or two symptoms of dependence; and
      subjects who met full criteria for DSM-IV alcohol dependence. Several variables
      significantly differentiated the three groups, including heavy drinking and
      family history of alcoholism. Group differences were reduced among 'orphans' and
      subjects with no symptoms who had at least one occasion of drinking five or more
      drinks in the year prior to the interview. The results provide support for the
      decision to require a minimum of three symptoms to make a diagnosis of alcohol
      dependence, for scientific as well as pragmatic reasons.

PMID- 10080048
TI  - Comparing levels of cocaine cue reactivity in male and female outpatients.
AB  - Thirty-eight female and 26 male cocaine-dependent outpatients were exposed to
      cocaine cues in a laboratory setting. Stimuli consisted of an audiotape of
      patients discussing cocaine use, a videotape of simulated cocaine preparation and
      use, and the handling of cocaine paraphernalia. Overall, the stimuli produced
      significant decreases in skin temperature and skin resistance, and significant
      increases in heart rate, self-reported drug states (high, craving, and
      withdrawal), and self-reported negative moods. Females were more likely to report
      increased craving in response to the cues than males, but there were no other
      gender differences in any of the responses. Levels of reactivity in females were
      comparable to the results of previous studies with all male samples. These
      results support the use of a constant set of cues in future treatment studies
      employing gender-balanced patient samples.

PMID- 10080049
TI  - Drinking patterns and problems, drug use and health services utilization: a
      comparison of two regions in the US general population.
AB  - While substance abuse has been found to be over-represented in some primary care
      settings, we do not know under what circumstances this association may vary, and
      whether it may be linked to differences in attitudes regarding alcohol use as
      reflected in regional rates of abstention and heavy or problem drinking. Data are
      reported from the Southern and Western regions of the 1995 National Alcohol
      Survey. Alcohol consumption variables were not found to be predictive of primary
      care utilization. Main effects were found for heavier drinking on emergency room
      (ER) use for an injury, and interactive effects of region were found for
      consequences of drinking, with those in the South who reported consequences more
      likely to have used the ER for either an injury or illness than those in the
      West. These data suggest that ER utilization may be related to regional
      differences in drinking patterns, while primary care utilization may not be.

PMID- 10080050
TI  - Deaths associated with inhalant abuse in Virginia from 1987 to 1996.
AB  - Inhalant abuse has existed for a considerable period of time and it is currently
      one of the most prevalent drug abuse problems in the world. One repercussion from
      using these compounds is that abuse may result in lethality. In an attempt to
      better understand the deaths associated with inhalant abuse, the authors surveyed
      the death records from the Commonwealth of Virginia from 1987 to 1996.
      Examination of the state records identified 39 deaths related to inhalant abuse
      during this time period. While no significant increase or decrease in the death
      rate was observed across the time period investigated, all regions of Virginia
      were affected, with the rates being highest in the northern and eastern regions
      of the state. Age of death ranged from 13 to 42 years with the majority of deaths
      (70%) occurring at 22 years of age or younger. Ninety-five per cent of the
      individuals were male, with volatile substance abuse deaths accounting for 0.3%
      of all deaths in males aged 13-22 years. The chief volatile substances used were
      gas fuels (46%), predominately butane and propane, chlorofluorocarbons (26%),
      chlorinated hydrocarbons and alkylbenzenes (21%), and other volatile substances
      including volatile anesthetics. Deaths associated with the abuse of butane and
      toluene were more likely to be traumatic, but all substances appeared capable of
      killing directly by their toxic effects, probably through cardiac and/or
      respiratory mechanisms. The ramifications of these findings for regulation and
      prevention are addressed.

PMID- 10080051
TI  - Do hallucinogens cause residual neuropsychological toxicity?
AB  - We collected and reviewed studies in which neuropsychological tests were
      administered to users of LSD or other hallucinogens. Interpretation of the
      studies is limited by various confounding variables, such as subjects' premorbid
      cognitive and personality function and prior use of other substances. At present,
      the literature tentatively suggests that there are few, if any, long-term
      neuropsychological deficits attributable to hallucinogen use. To better resolve
      this issue, however, it will be important to study larger samples of chronic,
      frequent hallucinogen users who have not often used other types of drugs.

PMID- 10080052
TI  - Methods used to detect drug abuse in pregnancy: a brief review.
AB  - A brief review of different methods adopted to assess foetal drug exposure is
      reported here. Various operative procedures have been described in the literature
      to detect drug abuse in pregnancy. All protocols can be clustered into two main
      groups: self-report and interview procedures and analytical methods. The latter
      can be performed on tissues and/or fluids withdrawn from the mother, from the new
      born or both. The aim of this review is to analyse the capability of these
      different techniques and the suitability of the biological specimens in view of
      the lack of consensus on a method of choice. The results obtained and the
      conclusions are different between various authors. A brief discussion on the
      capability of the different techniques and biological specimens adopted for this
      purpose is presented.

PMID- 10080053
TI  - Effects of phenytoin on cocaine self-administration in humans.
AB  - The goal of this pilot study was to determine the effects of phenytoin on cocaine
      self-administration in a human laboratory model. Subjects were randomized to
      either phenytoin (n = 6) or placebo (n = 7). Those assigned to phenytoin
      treatment received a single oral loading dose of 20 mg/kg. The phenytoin and
      placebo treatment groups did not differ in the number of tokens valued at $5,
      exchanged for cocaine. Similarly, the cardiovascular and subjective response to
      cocaine administration did not show a statistically significant treatment effect.
      In this laboratory model, phenytoin did not alter either the self-administration
      or effects of cocaine.

PMID- 10080054
TI  - [Post-traumatic palmar instability of the thumb metacarpophalangeal joint. The
      "other skier's thumb"].
AB  - "Passive" and "active" stabilizers give the thumb metacarpophalangeal (MP) joint
      the necessary palmar stability. It is possible to temporarily stabilize the joint
      by means of the flexor muscles in cases where there is an injury to the palmar
      ligaments due to hyperextension trauma. However, sudden severe or prolonged
      strain may lead to palmar instability and/or stress-related pain. In an
      experimental study, the MP joints of 40 specimen thumbs were hyperextended to
      varying degrees. The extent of tissue damage was evaluated during dissection.
      Between 1984 and 1992, in 72 cases with acute hyperextension injury of the thumb
      MP joint, we X-rayed the thumb under stress during primary examination. Habitual
      instability was excluded by comparing X-ray films under stress of the opposite
      uninjured thumb. The treatment of the lesion depends on the degree of instability
      documented by the X-ray films. Experimentally, we found only partial lesions or
      ruptures with only slight dislocation of the ligament ends in cases where the MP
      joint was hyperextended up to 30 degrees. In cases with hyperextension of 60
      degrees or more, there was usually a complete rupture of the ligaments or a
      fracture of the sesamoid bones with dislocation of the ligament ends as well as
      partial rupture of the thenar muscles. This injury pattern was also observed in
      clinical cases during surgery. Partial lesions of the palmar ligaments of the
      thumb MP joint can be treated conservatively with good results. In cases of
      complete palmar instability due to trauma, we saw better results after surgical
      reconstruction of the ligaments particularly in manual workers.

PMID- 10080055
TI  - [Supra-fascial elevated free forearm flap--indications, surgical technique and
      follow-up examination of the donor site defect].
AB  - From March 1995 to May 1997, 66 free radial forearm flaps were used for orofacial
      reconstructions. All flaps were elevated following the suprafascial technique.
      Donor-site closure was performed with split-thickness skin grafts in 54 cases,
      and with full-thickness skin grafts in 12 patients. Investigations after six
      months included grip strength, pulp-to-pulp pinch strength, range of motion as
      compared to preoperative values, aesthetical self-assessment, cold intolerance,
      and dysesthesias. The latter evaluation could be performed in 42 patients,
      whereas the complete follow-up protocol included 36 patients. Primary wound
      healing with immediate complete take of skin grafts was achieved in 93.9%. Grip
      strength and pulp-to-pulp pinch strength showed no decrease postoperatively. An
      impairment of range of motion of the wrist was observed in 2.8%. There was no
      cold intolerance. Aesthetical outcome was rated as good or fair in 97.3%. Slight
      numbness distally to the donor-site was found in 59.5%. The results of this
      prospective study show a superiority of suprafascial elevation of the radial
      foream flap as compared to the classic elevation technique, particularly in a
      higher rate of primary wound healing, thus avoiding impairment of range of motion
      and strength of the donor hand.

PMID- 10080056
TI  - [The lower trapezius muscle island flap. Anatomic principles and clinical
      relevance].
AB  - Up to now, there is no uniform anatomic description neither of the branches of
      the subclavian artery nor of the pedicle of the lower myocutaneous trapezius
      flap. A dissection study was carried out on 140 necks in 70 cadavers. Variations
      of the subclavian artery and its branches, vessel diameter at different levels,
      the course of the pedicle under the levator scapulae muscle, the arc of rotation
      of the island flap, and the variations of the segmental intercostal branches to
      the lower part of the trapezius muscle were examined. Results of this study
      enable us to suggest a new nomenclature for the branches of the subclavian
      artery, a proper pedicle definition, and a technique for safe flap elevation. The
      lower trapezius island flap is a thin and pliable myocutaneous flap with a
      constant pedicle which ensures safe flap elevation. This flap has the potential
      for a wider acceptance due to minor donor site morbidity, large arc of rotation,
      and an ample range of clinical applications in the head and neck area as an
      island flap as well as a free flap.

PMID- 10080057
TI  - [Free microvascular rectus abdominis muscle flap for soft tissue reconstruction
      of the lower leg and foot: results and donor site defect].
AB  - The free rectus abdominis muscle flap is now a routine procedure for the
      reconstruction of soft tissue defects in the lower extremity. We present the
      follow-up of 21 out of 27 patients operated in our clinic between 1986 and 1994.
      The recipient leg always showed a stable soft-tissue coverage. Clinical or
      radiological signs of osteitis were not found. In many of the cases, where the
      transplantion was to the ankle region, the muscle bulk led to an alteration of
      the shape of the leg, without impairment of function. When harvested through a
      low transverse abdominal incision, the aesthetic results in the donor site are
      convincing. The functional donor site defect is negligible as long as only a
      segment of the muscle is used. Abdominal muscle tests showed good results when
      only a segment of the muscle was used. The patients reported no impairment in
      daily life. Abdominal wall weakness was present only when the entire muscle was
      harvested. There was one hernia after postoperative wound infection and secondary
      wound healing. In all other cases, the abdominal wall was stable. In the
      segmental use of the free rectus abdominis muscle flap, the good results obtained
      in our examination correlate to the high degree of patient satisfaction.

PMID- 10080058
TI  - [Soft tissue reconstruction of the finger with free, posterior ramus of the
      anterior interosseous artery-based septo-cutaneous flap. Anatomy--technique--case
      examples].
AB  - In cases of larger soft-tissue defects of the fingers which cannot be covered
      with local or regional flaps, pedicled or even free flaps can be used. Pedicled
      flaps and most free flaps are too bulky and need several trimmings before a
      cosmetically and functionally satisfactory result is achieved. Free flaps used
      for soft-tissue reconstruction in digits should be thin and should have a low
      donor-site morbidity. The free flaps based on the anterior interosseous artery,
      especially the one based on the dorsal branch, are ideal for soft-tissue
      reconstruction of single digits. They are very thin and can be harvested in the
      same operative field. Donor-site morbidity is usually low. The clinical
      usefullness of this flap is shown in the reconstruction of three consecutive
      cases of severely damaged fingers.

PMID- 10080059
TI  - [Endoscopic forehead, face and neck lifting].
AB  - Endoscopic procedures are a more recent addition to the techniques of aesthetic
      plastic surgery of the head and neck region. This "buttonhole surgery" appeals
      particularly to patients and plastic surgeons alike because of tiny scars and
      reduced morbidity. The technique of video-assisted surgery with monitor control
      must be learned and practiced in teaching courses with hands-on experience in the
      laboratory. The indication for endoscopic forehead lifting is already well
      established. There is only a relative indication for endoscopic neck lifting. In
      the midface, the endoscope may more safely facilitate subperiosteal composite
      dissection. The results and the nature and rate of complications is comparable to
      conventional facelifting techniques. In the forehead, the endoscope renders the
      large bi-coronal scalping incision unnecessary. Good candidates are younger
      individuals with elastic skin and without major skin surplus. Long-term results
      are not yet available.

PMID- 10080060
TI  - [3-phase bone scintigraphy of microsurgically attached bone transplants as early
      graft survival assessment].
AB  - Vascularized bone grafts do not allow direct graft monitoring during the early
      postoperative period. The first two weeks are critical for the blood supply and
      viability of the graft. Three-phase bone scintigraphy, performed between the 7th
      and 14th postoperative day, was valuable in predicting the survival of
      vascularized bone grafts. It is a simple and safe method for the evaluation of
      blood supply of both the graft and the graft-surrounding tissue. Clinical data,
      obtained from studying 17 patients,/led to the conclusion that three-phase bone
      scintigraphy plays an important role in the process of decision-making on
      surgical reexploration.

PMID- 10080061
TI  - [Female circumcision: historical, sociological and medical aspects].
AB  - Female circumcision is a very old tradition still widely practised in Africa. The
      extent of female circumcision ranges from resection of the clitoridal prepuce (=
      sunnitic circumcision) to resection of labia minora and majora as well as
      clitoridectomy (= pharaonic circumcision). Wound approximation by sutures or scar
      contraction may cause partial closure of the vaginal orifice (= infibulation).
      Historical, sociological as well as medical aspects are discussed and
      reconstructive procedures described.

PMID- 10080062
TI  - [Fibrodysplasia ossificans progressiva. Case report].
AB  - A case of a nine-year-old boy with a rare connective tissue disorder is
      presented. Fibrodysplasia ossificans progressiva is a chronic progressive
      hereditary disease of unknown etiology and unfavourable prognosis. Any injury to
      tissue must be avoided as it induces further progression of the disease.

PMID- 10080063
TI  - [Fibrolipomatous hamartoma of the nerve--a rare etiology of macrodactyly. A case
      report].
AB  - Fibrolipomatous hamartoma of nerve is a rare, tumor-like fibro-fatty growth
      arising from the epi- and perineurium. It mainly affects peripheral nerves and
      the median nerve in particular. An association with Klippel-Trenaunay syndrome
      and macrodactyly has been described. We present a 30-year-old patient, in whom
      the diagnosis of Klippel-Trenaunay syndrome had been made at the age of two,
      based on macrodactyly of the right hand. Because of increasing functional
      limitation and pain, the patient was referred to our department, after
      angiographic exclusion of Klippel-Trenaunay syndrome, for operative reduction of
      the tumor. Histologic examination revealed a fibrolipomatous hamartoma of the
      nerve. Further treatment consisted of surgical tumor reduction, which resulted in
      satisfactory recovery of function in the right hand. After eight months follow
      up, the patient was able to perform all normal daily activities, and there was no
      evidence of recurrence of the lesion. Diagnostic evaluation of macrodactyly is
      necessary, since there may be an underlying cause such as fibrolipomatous
      hamartoma of a nerve, which if corrected early by surgical excision may prevent
      long-term disability.

PMID- 10080064
TI  - [Surgical treatment of Thibierge-Weissenbach syndrome and other calcinoses of the
      hand. Case report and review of the literature].
AB  - Soft-tissue calcifications in the hands may often be a sign of a systemical
      disease. The calcification then appears as a secondary manifestation of this
      disease. In that case, operative treatment ought to be a part of the overall
      treatment of the primary disease. When operating on fingers, the surgeon must pay
      attention not to compromise blood supply.

PMID- 10080065
TI  - The fourth-compartment syndrome: its anatomical basis and clinical cases.
AB  - We propose a new term, the "fourth-compartment syndrome" to describe chronic
      dorsal wrist pain of the fourth compartment. Five main causes responsible for
      this syndrome are thought to be as follows: 1. Ganglion involvement, including an
      occult ganglion; 2. Extensor digitorum brevis manus muscle; 3. Abnormal extensor
      indicis muscle; 4. Tenosynovialitis; 5. Anomaly or deformity of carpal bones.
      Should the above mentioned conditions occur in the fourth compartment, pressure
      within the fourth compartment increases, ultimately compressing the posterior
      interosseous nerve directly or indirectly. Anatomical studies of the fourth
      compartment of the wrist and the posterior interosseous nerve are presented and
      the fourth-compartment syndrome is summarized with twelve clinical cases (six
      cases of occult ganglions, two cases of extensor digitorum brevis manus, two
      cases of tenosynovialitis, one case of abnormal extensor indicis muscle, and one
      case of carpal bossing).

PMID- 10080066
TI  - [The interosseous palmaris muscle of the thumb. Results of an anatomic study of a
      muscle of the first ray].
AB  - In sixteen of twenty adult human cadaveric hands a muscle fascicle was isolated
      from the adductor pollicis muscle. It had osseous origins from the base of the
      first metacarpal bone and from the trapezium bone in eleven hands. These origins
      were connected by a fibrous arch, which was a soft tissue origin itself. In two
      of the sixteen hands, muscle fibers emerged from the palmar aspect of the first
      dorsal interosseous muscle near the radial artery. The findings can be explained
      by the ontogenesis of the human hand. The described muscle is neither a part of
      the oblique head of the adductor pollicis nor an equivalent to the three palmar
      interosseous muscles. In our dissections it was a constant muscle. Other studies
      have to show the exact function of the muscle. We postulate a stabilization of
      the carpometacarpal joint of the thumb.

PMID- 10080067
TI  - Laparoscopic techniques for gynecologic cancer: description and indications.
AB  - This article reviews the role of laparoscopic surgery in gynecologic oncology.
      The first part describes laparoscopic staging techniques. The second part
      describes surgical tumor-removal techniques. The third part discusses the
      indications for laparoscopic surgery in different types of gynecologic cancer.

PMID- 10080068
TI  - Future directions with taxane therapy.
AB  - The potential biochemical and genetic mechanisms by which a cell might experience
      a decreased sensitivity to taxanes and other drugs of this class are discussed in
      the first part of this article. The use of taxanes in the current gynecologic
      oncologic clinical setting is reviewed with special consideration given to the
      pharmacokinetics of taxane in relation to dose intensity and length of
      administration.

PMID- 10080069
TI  - Topoisomerase-I inhibitors in gynecologic tumors.
AB  - The first section of this article reviews recent studies that have clarified both
      the cellular role of topoisomerase I and the mechanisms of cytotoxicity of the
      topoisomerase inhibitors, the camptothecins. Different analogs of this new class
      of antitumor drug have been studied using various dose schedules in the treatment
      of refractory or recurrent gynecologic cancer. Response rates are between 13% and
      25%. The main toxic effects are hematologic and gastrointestinal, the latter
      remains problematic. Radiotherapy, alkylate, platinum analogues, and
      topoisomerase II inhibitors are currently being studied in combination with
      camptothecins.

PMID- 10080070
TI  - Clinical practice guidelines in the management of gynecologic malignancies.
AB  - The need for guidelines in managing gynecologic cancer is addressed in the first
      part of this article. Second, the guideline development process that enables the
      practitioner to judge the validity and usefulness of proffered guidelines is
      detailed. An important element in this discussion is an exploration of the
      shortcomings, either real or perceived, of the process. The last section focuses
      on issues relating to the implementation of guidelines and some of the obstacles
      that one may encounter as the programs evolve.

PMID- 10080071
TI  - End-of-life care in patients dying of gynecologic cancer.
AB  - In this article, the patient is considered from the time of disease recurrence,
      when any treatment is of necessity only palliative, through death. Good symptom
      control and psychosocial support are needed from the time of diagnosis. As death
      approaches, specific issues about cessation of active treatment and ethical
      issues over emergencies become important.

PMID- 10080072
TI  - Molecular aspects of ovarian cancer. Is gene therapy the solution?
AB  - Genetic abnormalities of cancer cells are complex and usually nonspecific.
      Genetic anomalies specific to ovarian cancer have not been reported. This article
      focuses on what molecular anomalies are known in ovarian cancer and describes the
      first trials that have used transfer of genes to reestablish a normal cellular
      function in this disease. Suicide gene therapy has been the prototype of this new
      therapeutic approach.

PMID- 10080073
TI  - The role of macrophages in antitumor defense of patients with ovarian cancer.
AB  - Macrophages have diverse effects on tumor biology, including neovascularization,
      growth rate, and stroma formation. Tumor-associated macrophages (TAMs) represent
      a major subpopulation of the mononuclear leukocytes present in malignant ascites
      of ovarian cancer patients. TAMs appear to participate in the immunologic
      antitumor defense mechanism through cytotoxic activities, such as direct cellular
      cytotoxicity and the release of cytokines, and may represent key targets for a
      variety of therapeutic interventions.

PMID- 10080074
TI  - Hormonal interactions in ovarian cancer.
AB  - According to the epidemiologic literature and the laboratory characterization of
      receptor content and molecular interactions, there is a relationship between the
      microenvironment of ovarian cancer and steroid hormones. Advances in our
      knowledge of the molecular-hormonal nature of ovarian cancer will help in
      designing a rationale for clinical trials in appropriate subsets of patients.
      However, currently, development of successful therapies and prevention strategies
      for women at risk remains a true challenge.

PMID- 10080075
TI  - Hormonal treatment of endometrial cancer.
AB  - This article summarizes the endocrine background of women with endometrial cancer
      at both peripheral and tissue levels, and the current status of clinical trials
      of hormonal, cytotoxic, and combination regimens. Because significant advances in
      systemic therapy are required to improve the prognosis of endometrial cancer,
      recommendations for future clinical investigations will be based on these recent
      biologic observations.

PMID- 10080076
TI  - Indications for adjuvant radiotherapy in endometrial carcinoma.
AB  - This article examines the impact of prognostic factors, adjuvant therapy, and
      randomized trials on the overall survival of patients with endometrial cancer.
      The potential role of radiation therapy as an adjuvant therapy, as well as the
      role of lymph node dissection, in the treatment of endometrial carcinomas is
      reviewed.

PMID- 10080077
TI  - Present knowledge of gynecologic sarcoma management.
AB  - Sarcomas arising in the gynecologic pelvic organs encompass different diseases
      with very different prognoses. This article attempts to define the different
      pathologies that arise from tissues of different histologic origin (mesodermal,
      stromal, and epithelial), and reviews the actual therapeutic knowledge based on
      the intrinsic prognosis of the sarcoma.

PMID- 10080078
TI  - Recent advances in gestational trophoblastic disease.
AB  - Advances in the last 20 years have led to a better understanding of the process
      of gestational trophoblastic disease (GTD), and consequently, to improved
      diagnosis, management, and prognosis. Patients with GTD should be registered at a
      trophoblastic disease center for follow-up, and those with persistent disease
      should receive chemotherapy, methotrexate, and folinic acid for low-risk disease,
      and EMACO (etoposide, actinomycin-D, methotrexate, vincristine, and
      cyclophosphamide) for high-risk disease, without loss of fertility. Most patients
      with relapsing or resistant disease can be treated effectively with surgery
      and/or cisplatin in EP/EMA (etoposide, platinum-etoposide, methotrexate,
      actinomycin-D) combination.

PMID- 10080079
TI  - Epidemiology of genital human papillomavirus.
AB  - Genital human papillomavirus (HPV) infection is the most common sexually
      transmitted viral infection and the major risk factor for cervical neoplasia
      worldwide; however, little is still known about the epidemiology and natural
      history of the disease. Prospective cohort studies currently being conducted will
      increase our knowledge and understanding of these issues and provide critical
      information for the formulation of future primary and secondary prevention
      strategies.

PMID- 10080080
TI  - Immunotherapeutic strategies for cervical squamous carcinoma.
AB  - Progress in developing preventive and therapeutic vaccines for HPV-associated
      diseases has been made in the last few years, but continued studies are needed to
      evaluate the clinical feasibility of different vaccination approaches and to
      determine a clinically effective and safe one. The perfect HPV vaccine will have
      both preventive and therapeutic capabilities, and because it is likely to be used
      world-wide, especially in developing countries, it must also have low production
      costs.

PMID- 10080081
TI  - Current developments in the treatment of newly diagnosed cervical cancer.
AB  - The International Federation of Gynecology and Obstetrics (FIGO) staging of
      cervical cancer relies on physical examination. However, surgical staging, which
      helps determine the extent of invasion of lymph nodes by cancer, is currently
      used more widely to define the need for additional therapies. Examples of these
      additional treatments include high-dose-rate brachytherapy techniques, extension
      of radiotherapy fields, surgery, concurrent chemotherapy and radiotherapy, and
      neoadjuvant chemotherapy prior to surgery. Currently there are many ongoing
      randomized studies that strive to define the risk-to-benefit ratio of these
      additional therapies.

PMID- 10080082
TI  - Contoured elastic-membrane microvalves for microfluidic network integration.
AB  - A contoured elastic-membrane microvalve is presented that enables integrated
      microfluidic processing at the network level. This method takes advantage of two
      ideas to improve performance: flexible elastic membranes (which enable high
      performance shutoff and reduced footprint), and three-dimensionally contoured
      valve geometries (which reduce dead volume, improve fluidic priming, and reduce
      susceptibility to cavitation at high fluid velocities). We describe the use of
      laser-induced etching for microfluidic manifold fabrication, discuss the
      nonlinear load-deflection behavior of elastic membranes that can occur below 30
      psi, and present flow-rate data for microvalves under inlet pressures of 0-20 psi
      with zero applied membrane pressure. Valve-closure data for inlet pressures of 0
      30 psi are presented for fully assembled microvalve structures. The microvalve
      structures under test were capable of turning off flows of > 20 microL/s. These
      flow rates were shown to be limited by inlet and outlet flow resistances and not
      by the valve structure itself, so that higher maximum flow rate capabilities
      should be readily achieved.

PMID- 10080083
TI  - Microfabricated modules for sample handling, sample concentration and flow
      mixing: application to protein analysis by tandem mass spectrometry.
AB  - The comprehensive analysis of biological systems requires a combination of
      genomic and proteomic efforts. The large-scale application of current genomic
      technologies provides complete genomic DNA sequences, sequence tags for expressed
      genes (EST's), and quantitative profiles of expressed genes at the mRNA level. In
      contrast, protein analytical technology lacks the sensitivity and the sample
      throughput for the systematic analysis of all the proteins expressed by a tissue
      or cell. The sensitivity of protein analysis technology is primarily limited by
      the loss of analytes, due to adsorption to surfaces, and sample contamination
      during handling. Here we summarize our work on the development and use of
      microfabricated fluidic systems for the manipulation of minute amounts of
      peptides and delivery to an electrospray ionization tandem mass spectrometer. New
      data are also presented that further demonstrate the potential of these novel
      approaches. Specifically, we describe the use of microfabricated devices as
      modules to deliver femtomole amounts of protein digests to the mass spectrometer
      for protein identification. We also describe the use of a microfabricated module
      for the generation of solvent gradients at nl/min flow rates for gradient
      chromatography-tandem mass spectrometry. The use of microfabricated fluidic
      systems reduces the risk of sample contamination and sample loss due to
      adsorption to wetted surfaces. The ability to assemble dedicated modular systems
      and to operate them automatically makes the use of microfabricated systems
      attractive for the sensitive and large-scale analysis of proteins.

PMID- 10080084
TI  - Micromachining in plastics using X-ray lithography for the fabrication of
      microelectrophoresis devices.
AB  - Micromachining was performed in polymethylmethacrylate (PMMA) using X-ray
      lithography for the fabrication of miniaturized devices (microchips) for
      potential applications in chemical and genetic analyses. The devices were
      fabricated using two different techniques: transfer mask technology and a Kapton
      mask. For both processes, the channel topography was transferred (1:1) to the
      appropriate substrate via the use of an optical mask. In the case of the transfer
      mask technique, the PMMA substrate was coated with a positive photoresist and a
      thin Au/Cr plating base. Following UV exposure, the resist was developed and a
      thick overlayer (approximately 3 microns) of Au electroplated onto the PMMA
      substrate only where the resist was removed, which acted as an absorber of the X
      rays. In the other technique, a Kapton film was used as the X-ray mask. In this
      case, the Kapton film was UV exposed using the optical mask to define the channel
      topography and following development of the resist, a thick Au overlayer (8
      microns) was electrodeposited onto the Kapton sheet. The PMMA wafer during X-ray
      exposure was situated directly underneath the Kapton mask. In both cases, the
      PMMA wafer was exposed to soft X-rays and developed to remove the exposed PMMA.
      The resulting channels were found to be 20 microns in width (determined by
      optical mask) with channel depths of approximately 50 microns (determined by x
      ray exposure time). In order to demonstrate the utility of this micromachining
      process, several components were fabricated in PMMA including capillary/chip
      connectors, injectors for fixed-volume sample introduction, separation channels
      for electrophoresis and integrated fiber optic fluorescence detectors. These
      components could be integrated into a single device to assemble a system
      appropriate for the rapid analysis of various targets.

PMID- 10080085
TI  - Rapid, automated nucleic acid probe assays using silicon microstructures for
      nucleic acid concentration.
AB  - A system for rapid point-of-use nucleic acid (NA) analysis based on PCR
      techniques is described. The extraction and concentration of DNA from test
      samples has been accomplished utilizing silicon fluidic microchips with high
      surface-area-to-volume ratios. Short (500 bp) and medium size (48,000 bp) DNA
      have been captured, washed, and eluted using the silicon dioxide surfaces of
      these chips. Chaotropic (GuHCl) salt solutions were used as binding agents. Wash
      and elution agents consisted of ethanol-based solutions and water, respectively.
      DNA quantities approaching 40 ng/cm2 of binding area were captured from input
      solutions in the 100-1000 ng/mL concentration range. For dilute samples of
      interest for pathogen detection, PCR and gel electrophoresis were used to
      demonstrate extraction efficiencies of about 50 percent, and concentration
      factors of about 10x using bacteriophage lambda DNA as the target. Rapid,
      multichannel PCR thermal cycling modules with integrated solid-state detection
      components have also been demonstrated. These results confirm the viability of
      utilizing these components as elements of a compact, disposable cartridge system
      for the detection of NA in applications such as clinical diagnostics, biowarfare
      agent detection, food quality control, and environmental monitoring.

PMID- 10080086
TI  - Molding of deep polydimethylsiloxane microstructures for microfluidics and
      biological applications.
AB  - Here we demonstrate the microfabrication of deep (> 25 microns) polymeric
      microstructures created by replica-molding polydimethylsiloxane (PDMS) from
      microfabricated Si substrates. The use of PDMS structures in microfluidics and
      biological applications is discussed. We investigated the feasibility of two
      methods for the microfabrication of the Si molds: deep plasma etch of silicon-on
      insulator (SOI) wafers and photolithographic patterning of a spin-coated
      photoplastic layer. Although the SOI wafers can be patterned at higher
      resolution, we found that the inexpensive photoplastic yields similar replication
      fidelity. The latter is mostly limited by the mechanical stability of the
      replicated PDMS structures. As an example, we demonstrate the selective delivery
      of different cell suspensions to specific locations of a tissue culture substrate
      resulting in micropatterns of attached cells.

PMID- 10080087
TI  - A tissue-like culture system using microstructures: influence of extracellular
      matrix material on cell adhesion and aggregation.
AB  - Special microenvironmental conditions are required to induce and/or maintain
      specific qualities of differentiated cells. An important parameter is the three
      dimensional tissue architecture that cannot be reproduced in conventional
      monolayer systems. Advanced tissue culture systems will meet many of these
      demands, but may reach their limits, especially when gradients of specific
      substances over distinct tissue layers must be established for long-term culture.
      These limitations may be overcome by incorporating microstructures into tissue
      like culture systems. The microstructured cell support presented consists of a
      flat array of 625 cubic microcontainers with porous bottoms, in which cells can
      be supplied with specific media from both sides of the tissue layer. Permanent
      cell lines and primary rat hepatocytes have been used to test the culture system.
      In order to define reproducible conditions for tissue formation and for cell
      adherence to the structure, several ECM (extracellular matrix) components were
      tested for coating of microstructured substrata. The described tissue culture
      system offers great flexibility in adapting the cell support to specific needs.

PMID- 10080088
TI  - Surfaces designed to control the projected area and shape of individual cells.
AB  - Materials with spatially resolved surface chemistry were designed to isolate
      individual mammalian cells to determine the influence of projected area on
      specific cell functions (e.g., proliferation, cytoskeletal organization).
      Surfaces were fabricated using a photolithographic process resulting in islands
      of cell binding N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS) separated
      by a nonadhesive interpenetrating polymer network [poly (acrylamide-co-ethylene
      glycol); P (AAm-co-EG)]. The surfaces contained over 3800 adhesive islands/cm2,
      allowing for isolation of single cells with projected areas ranging from 100
      microns 2 to 10,000 microns 2. These surfaces provide a useful tool for
      researching how cell morphology and mechanical forces affect cell function.

PMID- 10080089
TI  - The effects of the surface topography of micromachined titanium substrata on cell
      behavior in vitro and in vivo.
AB  - Surface properties, including topography and chemistry, are of prime importance
      in establishing the response of tissues to biomaterials. Microfabrication
      techniques have enabled the production of precisely controlled surface
      topographies that have been used as substrata for cells in culture and on devices
      implanted in vivo. This article reviews aspects of cell behavior involved in
      tissue response to implants with an emphasis on the effects of topography.
      Microfabricated grooved surfaces produce orientation and directed locomotion of
      epithelial cells in vitro and can inhibit epithelial downgrowth on implants. The
      effects depend on the groove dimensions and they are modified by epithelial cell
      cell interactions. Fibroblasts similarly exhibit contact guidance on grooved
      surfaces, but fibroblast shape in vitro differs markedly from that found in vivo.
      Surface topography is important in establishing tissue organization adjacent to
      implants, with smooth surfaces generally being associated with fibrous tissue
      encapsulation. Grooved topographies appear to have promise in reducing
      encapsulation in the short term, but additional studies employing three
      dimensional reconstruction and diverse topographies are needed to understand
      better the process of connective-tissue organization adjacent to implants.
      Microfabricated surfaces can increase the frequency of mineralized bone-like
      tissue nodules adjacent to subcutaneously implanted surfaces in rats. Orientation
      of these nodules with grooves occurs both in culture and on implants. Detailed
      comparisons of cell behavior on micromachined substrata in vitro and in vivo are
      difficult because of the number and complexity of factors, such as population
      density and micromotion, that can differ between these conditions.

PMID- 10080090
TI  - Numerical model of fluid flow and oxygen transport in a radial-flow microchannel
      containing hepatocytes.
AB  - The incorporation of monolayers of cultured hepatocytes into an extracorporeal
      perfusion system has become a promising approach for the development of a
      temporary bioartificial liver (BAL) support system. In this paper we present a
      numerical investigation of the oxygen tension, shear stress, and pressure drop in
      a bioreactor for a BAL composed of plasma-perfused chambers containing monolayers
      of porcine hepatocytes. The chambers consist of microfabricated parallel disks
      with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro
      for porcine hepatocytes, was curve-fitted using Michaelis-Menten kinetics for
      simulation of the oxygen concentration profile. The effect of different
      parameters that may influence the oxygen transport inside the chambers, such as
      the plasma flow rate, the chamber height, the initial oxygen tension in the
      perfused plasma, the OUR, and K(m) was investigated. We found that both the
      plasma flow rate and the initial oxygen tension may have an important effect upon
      oxygen transport. Increasing the flow rate and/or the inlet oxygen tension
      resulted in improved oxygen transport to cells in the radial-flow microchannels,
      and allowed significantly greater diameter reactor without oxygen limitation to
      the hepatocytes. In the range investigated in this paper (10 microns < H < 100
      microns), and for a constant plasma flow rate, the chamber height, H, had a
      negligible effect on the oxygen transport to hepatocytes. On the contrary, it
      strongly affected the mechanical stress on the cells that is also crucial for the
      successful design of the BAL reactors. A twofold decrease in chamber height from
      50 to 25 microns produced approximately a fivefold increase in maximal shear
      stress at the inlet of the reactor from 2 to 10 dyn/cm2. Further decrease in
      chamber height resulted in shear stress values that are physiologically
      unrealistic. Therefore, the channel height needs to be carefully chosen in a BAL
      design to avoid deleterious hydrodynamic effects on hepatocytes.

PMID- 10080091
TI  - Electrical, chemical, and topological addressing of mammalian cells with
      microfabricated systems.
AB  - This communication describes our work in electrical, topological, and chemical
      micromodification of surfaces to modulate cellular form and function. We have
      addressed the surface physico-chemico-mechano properties of cell culture
      substrates that play a role in modulating cellular behavior. Single factorial
      model systems have been built using techniques adapted from microlithography. The
      tools and techniques of microfabrication, if harnessed and used correctly, can be
      enabling in elucidating the underlying principles and fundamental forces driving
      the cell-substrate interface. Additionally, the long-term practical applications
      of microfabrication in medicine and biomaterial/tissue engineering lie in
      enabling "communication" with living cells/tissues at the cellular and
      subcellular levels.

PMID- 10080092
TI  - Microcontact printing for precise control of nerve cell growth in culture.
AB  - Microcontact printing, facilitated by silane linker chemistry and high-relief
      stamps, creates precise patterns of proteins, which in turn control growth of
      hippocampal neurons in culture. This additive, multi-mask technique permits
      several different molecules to be patterned on the same substrate. The covalent
      linker technology permits relatively long-term (two-week) compliance of neurons
      to the stamped pattern against a polyethylene glycol background. When polylysine
      was stamped adjacent to a laminin/polylysine mixture, neural somata and dendrites
      preferred the polylysine while axons prefer the mixture or the border between the
      two.

PMID- 10080093
TI  - The effect of graft caliber upon wall shear within in vivo distal vascular
      anastomoses.
AB  - Wall shear has been widely implicated as a contributing factor in the development
      of intimal hyperplasia in the anastomoses of chronic arterial bypass grafts.
      Earlier studies have been restricted to either: (1) in vitro or computer
      simulation models detailing the complex hemodynamics within an anastomosis
      without corresponding biological responses, or (2) in vivo models that document
      biological effects with only approximate wall shear information. Recently, a
      specially designed pulse ultrasonic Doppler wall shear rate (PUDWSR) measuring
      device has made it possible to obtain three near-wall velocity measurements
      nonintrusively within 1.05 mm of the vessel luminal surface from which wall shear
      rates (WSRs) were derived. It was the purpose of this study to evaluate the
      effect of graft caliber, a surgically controllable variable, upon local
      hemodynamics, which, in turn, play an important role in the eventual development
      of anastomotic hyperplasia. Tapered (4-7 mm I.D.) 6-cm-long grafts were implanted
      bilaterally in an end-to-side fashion with 30 deg proximal and distal anastomoses
      to bypass occluded common carotid arteries of 16 canines. The bypass grafts were
      randomly paired in contralateral vessels and placed such that the graft-to-artery
      diameter ratio, DR, at the distal anastomosis was either 1.0 or 1.5. For all
      grafts, the average Re was 432 +/- 112 and the average Womersley parameter,
      alpha, was 3.59 +/- 0.39 based on artery diameter. There was a sharp skewing of
      flow toward the artery floor with the development of a stagnation point whose
      position varied with time (up to two artery diameters) and DR (generally more
      downstream for DR = 1.0). Mean WSRs along the artery floor for DR = 1.0 and 1.5
      were found to range sharply from moderate to high retrograde values (589 s-1 and
      1558 s-1, respectively) upstream to high antegrade values (2704 s-1 and 2302 s-1,
      respectively) immediately downstream of the stagnation point. Although there were
      no overall differences in mean and peak WSRs between groups, there were
      significant differences (p < 0.05) in oscillatory WSRs as well as in the absolute
      normalized mean and peak WSRs between groups. There were also significant
      differences (p < 0.05) in mean and peak WSRs with respect to axial position along
      the artery floor for both DR cases. In conclusion, WSR varies widely (1558 s-1
      retrograde to 2704 s-1 antegrade) within end-to-side distal graft anastomoses,
      particularly along the artery floor, and may play a role in the development of
      intimal hyperplasia through local alteration of mass transport and mechano-signal
      transduction within the endothelium.

PMID- 10080094
TI  - Surfactant-spreading and surface-compression disturbance on a thin viscous film.
AB  - Spreading of a new surfactant in the presence of a pre-existing surfactant
      distribution is investigated both experimentally and theoretically for a thin
      viscous substrate. The experiments are designed to provide a better understanding
      of the fundamental interfacial and fluid dynamics for spreading of surfactants
      instilled into the lung. Quantitative measurements of spreading rates were
      conducted using a fluorescent new surfactant that was excited by argon laser
      light as it spread on an air-glycerin interface in a petri dish. It is found that
      pre-existing surfactant impedes surfactant spreading. However, fluorescent
      microspheres used as surface markers show that pre-existing surfactant
      facilitates the propagation of a surface-compression disturbance, which travels
      faster than the leading edge of the new surfactant. The experimental results
      compare well with the theory developed using lubrication approximations. An
      effective diffusivity of the thin film system is found to be Deff =
      (E*gamma)/(mu/H), which indicates that the surface-compression disturbance
      propagates faster for larger background surfactant concentration, gamma, larger
      constant slope of the sigma*-gamma* relation, -E*, and smaller viscous
      resistance, mu/H. Note that sigma* and gamma* are the dimensional surface tension
      and concentration, respectively, mu is fluid viscosity, and H is the unperturbed
      film thickness.

PMID- 10080095
TI  - Application of the Tsai-Wu quadratic multiaxial failure criterion to bovine
      trabecular bone.
AB  - As a first step toward development of a multiaxial failure criterion for human
      trabecular bone, the Tsai-Wu quadratic failure criterion was modified as a
      function of apparent density and applied to bovine tibial trabecular bone.
      Previous data from uniaxial compressive, tensile, and torsion tests (n = 139
      total) were combined with those from new triaxial tests (n = 17) to calibrate and
      then verify the criterion. Combinations of axial compression and radial pressure
      were used to produce the triaxial compressive stress states. All tests were
      performed with minimal end artifacts in the principal material coordinate system
      of the trabecular network. Results indicated that the stress interaction term F12
      exhibited a strong nonlinear dependence on apparent density (r2 > 0.99), ranging
      from -0.126 MPa-2 at low densities (0.29 g/cm3) to 0.005 MPa-2 at high densities
      (0.63 g/cm3). After calibration and when used to predict behavior of new
      specimens without any curve-fitting, the Tsai-Wu criterion had a mean (+/- SD)
      error of -32.6 +/- 10.6 percent. Except for the highest density triaxial
      specimens, most (15/17 specimens) failed at axial stresses close to their
      predicted uniaxial values, and some reinforcement for transverse loading was
      observed. We conclude that the Tsai-Wu quadratic criterion, as formulated here,
      is at best only a reasonable predictor of the multiaxial failure behavior of
      trabecular bone, and further work is required before it can be confidently
      applied to human bone.

PMID- 10080096
TI  - Finite element analysis of anterior tooth root stresses developed during
      endodontic treatment.
AB  - Vertical tooth root fractures are diagnostically challenging, frustrating, and an
      increasingly common cause of failure of tooth restoration. These vertical root
      fractures have been associated with many causes, including the endodontic process
      itself. To investigate these endodontic causes, various phases of crown
      replacement for an anterior tooth were modeled using nonlinear, plane strain
      finite element (FE) analysis. Stresses developed during obturation, post
      positioning, crown placement, and masticatory and occlusal loading of the
      restored tooth were estimated using this analysis method. The minimum
      (compressive) principal stress was greatest during obturation of cones 1 and 2,
      and during mastication of the restored tooth. Although these stresses were
      significant (-150 to -280 MPa), they did not exceed the compressive strength of
      dentin. The maximum (tensile) principal stresses, 160 to 300 MPa, were also
      observed during obturation of cones 1 and 2. These peak stresses exceed the
      dentin tensile strength.

PMID- 10080097
TI  - Viscoelastic characterization of mesenchymal gap tissue and consequences for
      tension accumulation during distraction.
AB  - Nonlinear viscoelastic analysis was used to characterize the time-dependent
      behavior of mesenchymal gap tissue generated during distraction osteogenesis. Six
      (n = 6) lengthened tibiae were harvested from New Zealand white rabbits at 18
      days. This gap tissue was subjected to a series of step displacement tests of
      increasing magnitude, and force relaxation behavior was monitored. Isochrones in
      stress-strain space were fit to odd cubic functions of strain. An analytic
      expression, linear in both e and e3, was developed to predict stress accumulation
      within the gap tissue as a function of time during distraction. Stress relaxation
      functions were described well by two-term Prony series. The two time constants
      determined from mechanical testing results were consistent, suggesting the
      presence of two fundamental physiologic relaxation processes. Gap tissue stresses
      were predicted to rise considerably during early stages of lengthening when
      distraction magnitudes exceeded the clinical norm of 0.25 mm. These differences
      in tension accumulation were less pronounced by the time lengthening was
      completed. Specifically, these results may in part explain clinical observations
      of decreased bone regeneration and altered tissue proliferation and
      differentiation at higher distraction rates. More generally, this work provides a
      framework for the rigorous characterization of the viscoelastic properties of
      biologic tissues ordinarily exposed to step strains.

PMID- 10080098
TI  - Mechanical properties of collagen fascicles from the rabbit patellar tendon.
AB  - Tensile and viscoelastic properties of collagen fascicles of approximately 300
      microns in diameter, which were obtained from rabbit patellar tendons, were
      studied using a newly designed micro-tensile tester. Their cross-sectional areas
      were determined with a video dimension analyzer combined with a CCD camera and a
      low magnification microscope. There were no statistically significant differences
      in tensile properties among the fascicles obtained from six medial-to-lateral
      locations of the patellar tendon. Tangent modulus, tensile strength, and strain
      at failure of the fascicles determined at about 1.5 percent/s strain rate were
      216 +/- 68 MPa, 17.2 +/- 4.1 MPa, and 10.9 +/- 1.6 percent (mean +/- S.D.),
      respectively. These properties were much different from those of bulk patellar
      tendons; for example, the tensile strength and strain at failure of these
      fascicles were 42 percent and 179 percent of those of bulk tendons, respectively.
      Tangent modulus and tensile strength of collagen fascicles determined at 1
      percent/s strain rate were 35 percent larger than those at 0.01 percent/s. The
      strain at failure was independent of strain rate. Relaxation tests showed that
      the reduction of stress was approximately 25 percent at 300 seconds. These stress
      relaxation behavior and strain rate effects of collagen fascicles differed
      greatly from those of bulk tendons. The differences in tensile and viscoelastic
      properties between fascicles and bulk tendons may be attributable to ground
      substances, mechanical interaction between fascicles, and the difference of crimp
      structure of collagen fibrils.

PMID- 10080099
TI  - A hub dynamometer for measurement of wheel forces in off-road bicycling.
AB  - A dynamometric hubset that measures the two ground contact force components
      acting on a bicycle wheel in the plane of the bicycle during off-road riding
      while either coasting or braking was designed, constructed, and evaluated. To
      maintain compatibility with standard mountain bike construction, the hubs use
      commercially available shells with modified, strain gage-equipped axles. The axle
      strain gages are sensitive to forces acting in the radial and tangential
      directions, while minimizing sensitivity to transverse forces, steering moments,
      and variations in the lateral location of the center of pressure. Static
      calibration and a subsequent accuracy check that computed differences between
      applied and apparent loads developed during coasting revealed root mean squared
      errors of 1 percent full-scale or less (full-scale load = 4500 N). The natural
      frequency of the rear hub with the wheel attached exceeded 350 Hz. These
      performance capabilities make the dynamometer useful for its intended purpose
      during coasting. To demonstrate this usefulness, sample ground contact forces are
      presented for a subject who coasted downhill over rough terrain. The dynamometric
      hubset can also be used to determine ground contact forces during braking
      providing that the brake reaction force components are known. However, compliance
      of the fork can lead to high cross-sensitivity and corresponding large (> 5
      percent FS) measurement errors at the front wheel.

PMID- 10080100
TI  - Interleukin-18 and interleukin-1 beta: two cytokine substrates for ICE (caspase
      1).
AB  - This special article deals with the role of processing enzymes in the generation
      of bioactive cytokines, particularly IL-1 beta and the novel cytokine IL-18,
      which was formerly called IFN gamma-inducing factor (IGIF). The "classical"
      pathways of cytokine processing are described, as well as the importance of
      alternative cleavage enzymes. The topic of this review also concerns the biology
      of IL-18. The regulation of IL-18 production, the IL-18 receptor complex, and the
      biological effects of this novel cytokine are described.

PMID- 10080101
TI  - Dendritic cells: a link between innate and adaptive immunity.
AB  - Dendritic cells (DC) constitute a unique system of cells able to induce primary
      immune responses. As a component of the innate immune system, DC organize and
      transfer information from the outside world to the cells of the adaptive immune
      system. DC can induce such contrasting states as active immune responsiveness or
      immunological tolerance. Recent years have brought a wealth of information
      regarding DC biology and pathophysiology, that shows the complexity of this cell
      system. Although our understanding of DC biology is still in its infancy, we are
      now in a position to use DC-based immunotherapy protocols to treat cancer and
      infectious diseases.

PMID- 10080102
TI  - Stability of natural self-reactive antibody repertoires during aging.
AB  - We have used a quantitative immunoblotting technique to analyze the repertoires
      of self-reactive antibodies in serum samples obtained from the same five healthy
      adults over a 25-year interval. The average age of the donors was 43 years at the
      time of the first serum sample and 69 years at the time of the second serum
      sample. The antibody repertoires of IgM and IgG were found to be strikingly
      similar among individuals in both early and late samples. Densitometric profiles
      of self-reactivity of serum IgM and of purified serum IgG remained unchanged over
      the 25-year interval. The total reactivity of serum IgG decreased significantly
      over the 25-year period. The observed stability of the natural self-reactive IgM
      and IgG antibody repertoires with aging supports the view that autoreactive B
      cells in the normal immune system are positively selected for reactivity with a
      limited set of immunodominant self-antigens throughout life.

PMID- 10080103
TI  - Modulation of antioxidant enzymes and apoptosis in mice by dietary lipids and
      treadmill exercise.
AB  - The current experiments were designed to study the effect of dietary n-6 and n-3
      polyunsaturated fatty acids on antioxidant enzyme activity and dexamethasone
      (DEX)-induced apoptosis in spleen cells of sedentary (Sed) and treadmill
      exercised (Ex) ICR male mice. Two-month-old mice maintained on AIN 76 formula
      diet, supplemented with either 5% corn oil (CO) or 5% fish oil (FO) diets, were
      trained on a treadmill to run from 45 to 50 min 1 km/day, 6 days a week for 12
      weeks. After 12 weeks of exercise, both Sed and Ex groups were sacrificed. Blood
      and various tissues, including spleen, were collected asceptically. Increased
      serum and spleen homogenate peroxide [malondialdehyde (MDA)] levels were observed
      in mice fed FO (n-3 PUFA) diets, compared to mice fed CO (n-6 PUFA). However,
      exercise did not alter MDA levels in either CO- or FO-fed mice. Feeding n-3 PUFA
      significantly increased superoxide dismutase (SOD), catalase, and glutathione
      peroxidase activity of spleen homogenates. Exercise also significantly increased
      SOD and peroxidase in CO-fed animals, whereas catalase, glutathione peroxidase,
      and glutathione transferase were higher in FO-fed mice, compared to the Sed
      group. Apoptosis and necrosis were quantitated in splenocytes incubated with or
      without 1 microM Dex in RPMI medium for 8 and 24 hr. Cells were stained with
      Annexin V and propidium iodide (PI) for apoptotic and necrotic cells. FO-fed mice
      showed higher apoptosis (64 vs 50%) and necrosis (40 vs 22%) in spleen cells than
      CO-fed mice. Cells from FO-fed mice, incubated in medium alone, showed increased
      apoptosis (112%) 24 hr after incubation, and necrosis (37 and 70%) at 8 and 24 hr
      of incubation, compared to CO-fed mice. In Ex group, apoptosis was increased in
      both CO- and FO-fed mice only at 24 hr after incubation. In summary, these
      results indicate that FO (n-3 PUFA-enriched) diets increase apoptosis and
      antioxidant enzyme activity in spleen cells, probably due to elevated lipid
      peroxides.

PMID- 10080104
TI  - Further characterization of the autoantibody response of Palmerston North mice.
AB  - PN mice spontaneously develop, with age, a lupus-like disease. The present study
      further evaluated autoantibody production in female PN mice. As early as 1 month
      of age, all PN mice had detectable IgM antibodies to dsDNA and ssDNA and two
      thirds produced IgM anticardiolipin antibodies. By 3 months of age, all PN mice
      exhibited evidence of isotype switch in their autoantibody response; 88-100% had
      serum IgG antibodies to ssDNA and dsDNA, respectively. By 6-12 months of age,
      essentially all female PN mice had IgG antibodies to ssDNA, dsDNA, cardiolipin
      and other phospholipids (PS, PC, PI, and PG), and IgG and 63% produced IgG anti
      mouse erythrocyte antibodies. In addition, 50-100% produced IgA antibodies to
      dsDNA and ssDNA, and one-third produced IgA anti-IgG antibodies. Antibodies to
      U1RNP and Sm were present in 81% of 6- to 12-month-old PN mice and 39-94% had IgG
      or IgM antibodies to mouse thymocytes. Although all four IgG isotypes were
      represented in the anti-dsDNA response, IgG1 antibodies dominated the IgG
      anticardiolipin response. The presence of IgA autoantibodies and the predominance
      of IgG1 in the IgG anticardiolipin response suggest that IL-4 and either IL-5
      and/or TGF-beta serve as B cell stimulatory cytokines for autoreactive B cells in
      PN mice.

PMID- 10080105
TI  - Expression of CD80 and CD86 on peripheral blood T lymphocytes in patients with
      systemic lupus erythematosus.
AB  - CD80 and CD86 were detected in high amounts on circulating T cells in the
      peripheral blood of some patients with systemic lupus erythematosus (SLE), using
      flow cytometry and monoclonal antibodies. Patients with other connective tissue
      diseases did not have a high percentage of T cells expressing CD80 or CD86 in
      their peripheral blood. CD80 was expressed mainly on CD4 T cells, whereas CD86
      was expressed on CD8 T cells, and these two populations were associated with
      particular clinical features. These two molecules were expressed on different T
      cell populations and might have different roles in the generation and regulation
      of immune responses. Since high expression of CD86 on T cells was detected much
      earlier than the appearance of clinical features and a high titer of anti-DNA
      antibody, it may be a useful parameter for predicting the flare of SLE.

PMID- 10080106
TI  - Acute alcohol consumption attenuates interleukin-8 (IL-8) and monocyte
      chemoattractant peptide-1 (MCP-1) induction in response to ex vivo stimulation.

PMID- 10080108
TI  - Abstracts from the 1999 annual meeting of the American Glaucoma Society.

PMID- 10080107
TI  - Generation of MHC class I-restricted cytotoxic T cell lines and clones against
      colonic epithelial cells from ulcerative colitis.
AB  - We established CTL lines and clones against colonic epithelial cells from PBLs of
      patients with ulcerative colitis by continuous stimulation with HLA-A locus
      matched colonic epithelial cell lines. We developed a nonradioactive europium
      release cytotoxicity assay to detect CTLs. PBLs from 3 of 12 patients but not
      from any of 14 normal controls who shared at least one haplotype of HLA-A locus
      with two colonic epithelial cell lines, CW2 and ACM, showed increased
      cytotoxicity against these lines. Three CTL lines established from the PBLs of
      patients showed increased cytotoxicity against HLA-A locus-matched CW2 or ACM but
      not against matched lung or esophagus cell lines. The phenotypes of CTL lines
      were alpha beta-TCR+ CD3+ CD8+ CD16-. The CTL line MS showed increased
      cytotoxicity against freshly isolated colonic epithelial cells but not against
      cells with a different HLA-A locus. Two CTL clones were generated from MS and
      clone 3-2, expressing CD3+ CD8+ CD4- CD56-, showed high MHC class I-restricted
      cytotoxicity against the colonic epithelial cells. These results indicated that
      CTLs against colonic epithelial cells may contribute to epithelial cell damage in
      ulcerative colitis.

PMID- 10080109
TI  - Solubilization of liposomes by weak electrolyte drugs. II. Cefotaxime.
AB  - The solubilization of dimyristoylphosphatidylcholine (DMPC) liposomes by the weak
      electrolyte drug, cefotaxime (CFX), has been studied as a function of pH, DMPC,
      temperature, presence of cholesterol (CHOL), and method of liposome preparation.
      At 7.5 mM CFX the lag time for solubilization increased, the rate of
      solubilization decreased, and the minimum turbidity reached increased as a
      function of DMPC at pH 1.0 and 40 degrees C. Solubilization was most pronounced
      at pHs below the pKa but inhibited at least one pH unit above the pKa. The
      critical mole ratio of unionized CFX:DMPC, Rec, for solubilization was estimated
      to be 0.12. Reducing the temperature slowed the rate of solubilization as did the
      addition of CHOL. Encapsulation of CFX in liposomes did not significantly reduce
      CFX degradation,. k1 = 0.048 h-1 at 40 degrees C and a complex of DMPC and a
      degradation product of CFX precipitated as rectangular crystals. As a result, an
      increase in the turbidity of solubilized systems was observed from about 20 h to
      48 h depending on the conditions. Liposomes in the gel state or with at least 20%
      CHOL did not undergo an apparent reversal of solubilization. It is concluded that
      the inclusion of weak electrolyte drugs existing predominantly as the unionized
      species in liquid crystalline state liposomes may undergo a slow solubilization
      process not necessarily recognized during characterization.

PMID- 10080110
TI  - Effect of manufacturing conditions on the formation of double-walled polymer
      microspheres.
AB  - This paper discusses the optimization of the solvent evaporation process to
      produce double-walled (DW) microspheres in a single-step. Five process variables
      were studied: polymer solution concentration, polymer weight ratio, polymer
      solution volume ratios, encapsulation temperature, and air flow rate across the
      top of the encapsulation vessel. The effects of these variables on the process
      efficiency (defined here as the percentage of microspheres with a DW
      configuration compared to the total number of microspheres) were examined. Total
      polymer concentrations of less than 20% (w/v) produced microspheres with high
      efficiency, with phase separation consistent across all size fractions in each
      batch. Changing the volume ratio of the two polymer solutions had no significant
      effect on the process efficiency. The weight ratio of the polymers greatly
      influenced the process efficiency, resulting in a low 63% efficiency for the 1:3
      Poly-L-lactide (PLLA): Poly(carboxyphenoxypropane-co-sebacic)anhydride 20:80
      (P(CPP:SA 20:80)) weight ratio and 0% for the 3:1 weight ratio. The 1:3 weight
      ratio also caused the polymers to reverse their orientation, although the
      efficiency for this switch was still relatively low. The temperature of the non
      solvent bath affected the efficiency of certain pairs of polymers, but not all.
      The PLLA/Poly(lactide-co-glycolide) 50:50 (PLGA) pair was most sensitive to
      temperature, due to the chemical similarity of the two polymers which narrowed
      the range of acceptable conditions for encapsulation. Pairs of polymers which
      phase separated readily (e.g. polystyrene and PLLA) were the least sensitive to
      temperature changes. Process yield and size distribution show no clear trends
      with respect to air flow rate across the top of the reaction vessel. The
      efficiency of the process to produce DW microspheres increased and the process
      time decreased with increasing air flow across the surface of the encapsulation
      vessel.

PMID- 10080111
TI  - Microencapsulation and testing of the agricultural animal repellent, Daphne.
AB  - The microencapsulated animal repellent Daphne was prepared by in situ
      polymerization of melamine-formaldehyde prepolymer with styrene-maleic acid
      anhydride copolymer as a modifying agent. Pure Daphne (a mixture of essential
      oils and other volatile compounds) and Daphne (45 wt%) diluted with
      isopropylmyristate (55 wt%) were used as core materials. Three types of
      formulations were prepared: (1) aqueous suspension concentrates, to be diluted
      for spraying, (2) thickened pastes with microcapsules for coating tree bark, and
      (3) textile, paper and metal strips, coated or impregnated with microcapsules. In
      field testing, all formulations with microcapsules showed a prolonged effect in
      comparison with non-encapsulated Daphne. The repelling effect on animals was
      stronger in summer and weaker in winter, when the pressure of the animals was
      much more intense, and diffusion of repellent from the microcapsules was reduced
      due to low temperatures. However, pastes for the bark and non-woven textile
      strips impregnated with microencapsulated Daphne showed good repelling effect
      against deer and rabbits in the winter period.

PMID- 10080112
TI  - Cephradin-plaga microspheres for sustained delivery to cattle.
AB  - In the field of controlled drug delivery, most of the reported work is aimed at
      introducing new systems, or at providing basic information on the critical
      parameters which affect release profiles in vitro and occasionally in vivo. The
      situation is totally different when one wants to fulfil the specific requirements
      imposed by the marketing of a sustained release device to be used in humans or in
      animals eaten by human beings. The control of the release characteristics is then
      a difficult challenge. In this work, attempts were made to combine cephradin, a
      hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a
      poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering
      the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period
      after i.m. injection. PLAGA aliphatic polyesters were selected because they are
      already FDA approved as matrices. The solvent evaporation technique using PVA as
      the emulsion stabilizer was selected because it is efficient and can be extended
      to an industrial scale. Various experimental conditions were used in order to
      obtain the highest encapsulation yields compatible with the desired
      specifications. Decreasing the volume of the aqueous phase and adding a water
      miscible organic solvent/non-solvent of cephradin failed. In contrast,
      microspheres containing up to 30% cephradin were prepared after addition of
      sodium chloride to the aqueous dispersing phase. The amount of entrapped drug was
      raised to 40% by decreasing the temperature and the pressure. Preliminary
      investigations using dogs showed that 20% cephradin microspheres prepared under
      these conditions extended the presence of cephradin in the blood circulation up
      to 48 h. Increasing the load led to higher blood concentrations but shorter
      sustained release. The fact that the microspheres were for cattle limited the
      volume of the injection and thus the amount of microspheres to be administered.
      The other limiting factors were related to microsphere morphology.

PMID- 10080113
TI  - Release characteristics of chitosan treated alginate beads: I. Sustained release
      of a macromolecular drug from chitosan treated alginate beads.
AB  - Alginate and chitosan treated alginate beads were prepared and compared as an
      oral controlled release system for macromolecular drugs. Dextran (M.W. 70,000)
      was used as a model substance. The beads were prepared by the ionotropic gelation
      method and the effect of various factors (alginate, chitosan, drug and calcium
      chloride concentrations, the volume of external and internal phases and drying
      methods) on bead properties were investigated. The addition of chitosan increased
      the drug loading capacity of the beads, and larger beads were obtained in the
      presence of chitosan. On the other hand, addition of chitosan in the gel
      structure reduced the drug release from beads. The erosion of the beads was
      suppressed by chitosan treatment. The drying method was important to the
      properties of the chitosan-alginate beads. It is proposed that chitosan treated
      alginate beads may be used as a potential controlled release system of such
      macromolecules.

PMID- 10080114
TI  - Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug
      incorporation and physicochemical characterization.
AB  - Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled
      drug delivery. The lipophilic model drugs tetracaine and etomidate were
      incorporated to study the maximum drug loading, entrapment efficacy, effect of
      drug incorporation on SLN size, zeta potential (charge) and long-term physical
      stability. Drug loads of up to 10% could be achieved whilst simultaneously
      maintaining a physically stable nanoparticle dispersion. Incorporation of drugs
      showed no or little effect on particle size and zeta potential compared to drug
      free SLN. The optimized production parameters previously established for drug
      free SLN dispersions can therefore be transferred to drug-loaded systems to
      facilitate product development.

PMID- 10080115
TI  - Rhizobacteria microencapsulation: properties of microparticles obtained by spray
      drying.
AB  - Rhizobacteria Pseudomonas fluorescens-putida were microencapsulated in Eudragit
      by spray-drying. These microparticles are subsequently included in seed coating
      or pelleting material. The survival of the bacterial cell in microparticles were
      studied under different levels of relative humidity (RH): 0, 33, 55 and 100%. The
      protective effects of silica, present in certain formulations, were demonstrated
      at the relative humidities of 33 and 55%. The release of the encapsulated
      bacteria was also studied over time. The release was fast, the bacteria being
      observed at 15 min immersion of the Eudragit microparticles in an aqueous-buffer
      medium at 20 degrees C. This result, related to the physicochemical character of
      the coating polymer, showed that water was the triggering element for the release
      of rhizobacteria. Compatibility studies between two film-forming agents used for
      seed coatings and the encapsulated bacteria, as well as wettability measures of
      tableted microparticles, were carried out. The bacterial survival was good with
      the seed coating agent, Sepiret 1039G, and the wettability measurements of
      agglomerated microparticles were in accord with the rapid release of the
      microencapsulated bacteria. The application of microparticles containing
      rhizobacteria on seeds can now be considered for preliminary trials.

PMID- 10080116
TI  - Preparation of albumin microspheres by an improved process.
AB  - Albumin is widely used to prepare microspheres and microcapsules. In this study
      microspheres were prepared by the suspension crosslinking method for the first
      time in the absence of any surface active agent, using paraffin oil as the
      dispersion medium and formaldehyde as the crosslinking agent. The microspheres
      thus obtained were characterized using a Scanning Electron Microscope and found
      to be spherical and having a particle size distribution in the range 50-400
      microns. A preliminary drug release study of chlorothiazide in-vitro indicated a
      diffusion controlled release of the drug. This method, being simple and cost
      effective, could be a promising technique for the large scale manufacture of
      microspheres.

PMID- 10080117
TI  - Ocular drug targeting by liposomes and their corneal interactions.
AB  - Topical drug delivery is preferred in the eye to avoid under or over medication
      and undesired side effects of systemic administration. In order to maintain
      adequate drug levels in ocular tissues, frequent drug installation is necessary
      in vision threatening conditions like glaucoma, corneal ulcers due to microbial
      infections, etc. Only a part of the installed drug reaches the aqueous humor and
      the rest of it is drained by the nasolacrimal duct. Positively charged liposomes
      have been found to enhance the penetration of drugs into the cornea. The present
      study was conducted to visualize the interaction of liposomes with the cornea.
      Briefly, positively charged liposomes entrapped with Carboxyfluorescein (CF),
      Propidium iodide (PI), Horseradish peroxidase (HRP), Biotin, Hydroxy benzimide
      (Hoechst No: 33258), and Ethoxy benzimide (Hoechst No: 33342) were prepared by
      sonication. Their size and shape were analysed by laser dynamic light spectra and
      electron microscopy, respectively. The liposome encapsulated and free materials
      in buffer were instilled, in a volume of 20 microliters, into eyes of
      anesthetized albino rats. After 30 min and 1 h, the eyes were enucleated and
      quickly processed for cryosections of 3-5 microns thickness. The interaction of
      liposome entrapped propidium iodide and HRP was visualized on the outer
      epithelium of the cornea after specific processing.

PMID- 10080118
TI  - Preparation of liposomes by reverse-phase evaporation using alternative organic
      solvents.
AB  - The organic solvents employed in liposome preparation, such as chlorinated
      solvents, diethyl ether or methanol, although usually removed by evaporation, may
      remain as traces in the final formulation representing a possible risk for human
      health and influencing the stability of the vesicles. In order to solve the above
      mentioned disadvantages, this paper describes the use of different organic
      solvents, namely ethanol, ethyl acetate and two mixtures of ethanol/ethyl
      acetate, for the production of liposomes by the reverse phase evaporation
      technique. After preparation, liposomes were extruded through polycarbonate
      filters and then characterized by size and encapsulation efficacy. As model drugs
      retinyl acetate and sodium cromoglycate have been used. The association yield for
      the hydrophilic drug and the encapsulation yield for the hydrophilic model drug
      were found, in all the liposome preparations, to be satisfactory. In particular,
      the use of more polar organic solvents (with respect to diethyl ether) appear to
      enhance the encapsulation of the hydrophilic drug, sodium cromoglycate. The use
      of alternative organic solvents to diethyl ether can be proposed with the aim of
      reducing the toxic problems associated with the presence of residual traces of
      organic solvents in the final liposome formulation.

PMID- 10080119
TI  - [Exploratory analysis of risk factors of acute inner ear dysfunctions].
AB  - Aside from the clinical picture, the frequent occurrence of vascular risk factors
      favors a vascular pathogenesis of acute sensorineural hearing loss. However, the
      data on the association of vascular risk factors with sensorineural hearing loss
      are controversial. Achieving a sufficient number of patients and establishing a
      suitable control group is difficult. We analyzed the data of 393 patients
      suffering from acute sensorineural hearing loss. Risk factors, general,
      audiological, and laboratory parameters were investigated. Mean hearing loss and
      remission during 10 days of hospital treatment were calculated. The patient group
      was divided into patients with a certain risk factor and those without this risk
      factor, and mean remission and hearing loss were compared. Patients suffering
      from hyperlipidemia or hypotension had substantial and significantly higher mean
      hearing losses than patients not suffering from these diseases. Thrombosis,
      embolism, and hypertension were associated with a significantly worse remission
      of hearing loss. Repeated episodes of sensorineural hearing loss showed a
      significant worse remission, but less mean hearing loss before therapy. Smoking,
      diabetes mellitus, infections of the upper airways, and allergies had no
      influence on remission and mean hearing loss.

PMID- 10080120
TI  - [Ear thermometry from the otologic viewpoint].
AB  - Tympanic thermometry (TT) detects infrared emissions reaching a probe placed in
      the ear canal directed toward the tympanic membrane. This has been reported to be
      an ideal site for clinical temperature measurements. TT provides results rapidly,
      taking only one second. It is clean, safe, and there is no mucous membrane
      contact. Studies have primarily focused on the use of TT in pediatric office and
      emergency room settings. In the literature published to date, the otological
      viewpoint has not played an important role. Specially there is no systematic
      investigation of the influence of cerumen on TT. Twenty patients were examined.
      All of them had a complete obstruction of the auditory canal by cerumen. TT was
      performed before and after the removal of cerumen. It was found to have a
      significant impact on the ear temperature reading. After the removal, the
      temperature was higher by 0.5 degree C. In conclusion, one should consider that
      there can be a systematic error when using TT to determine body temperature.
      Nevertheless there are some important advantages compared to other methods of
      temperature measurements. Especially in the hands of physicians and nurses TT is
      accurate and can be recommended. However, at home in the hand of non
      professionals there are some limitations and restrictions, particular when used
      in children. Further studies will have to be performed with a focus on otological
      problems and to determine the accuracy of TT in the non-professional user.

PMID- 10080121
TI  - [Selection of a cochlear implant and results of implantation].
AB  - BACKGROUND: The cochlear implant is the therapy of choice for completely deaf
      patients. With this concept speech communication can be restored or developed.
      METHODS: The selection of the implant system may depend on different factors. As
      long as speech competence is thought to be of highest importance, a fast
      stimulation strategy involving a state of the art cochlear implant that provides
      1500 Hz for every single electrode is close to the optimum. Further parameters
      include deep insertion into the cochlea (normally 30 mm) and other technical
      details. RESULTS: With these conditions fulfilled, about 2/3 of the adult deaf
      patients will later be able to use a telephone. Children who received implants in
      due time and do not have other cerebral defects will be partly able to meet with
      the requirements of normal schools.

PMID- 10080122
TI  - [Improvement of hearing aid fitting with digital aids and new fitting
      strategies].
AB  - Hearing aids with digital signal processing demonstrate a large dynamic range
      with negligible distortion and no significant inherent noise. Furthermore, many
      acoustic parameters allow the compensation of even severe hearing loss, and the
      adjustment is extremely accurate. However, the new hearing aid generation not
      only requires computerized fitting, but also an experienced examination with new
      integrated fitting procedures. In addition to in situ measurement, the hearing
      aid fitting should include not only the Freiburg speech test, but also the
      Gottingen sentence test and the monosyllable rhyme test with different noises,
      for example the Fastl noise or the Doring babble noise. Loudness scaling with
      different methods is particularly important.

PMID- 10080123
TI  - [Clinical aspects of the osteolytic (inflammatory) phase of cochlear
      otosclerosis].
AB  - During the last years it has been demonstrated that the active stage of
      otosclerosis (French: otospongieuse) is caused by an osteolytic inflammation
      associated with a measles-virus infection. Under influences that are not yet well
      understood (e.g. estrogens), the osteolytic process is arrested and changed to
      osteoblast activity accompanied by new bone formation. This latter process can be
      understood as a scar formation. If the process takes place within the area of the
      oval window, it results in fixation of the stapes and conductive hearing loss.
      When the otosclerotic process is restricted to the cochlea, clinical signs are
      not well defined. We report on exemplary cases of progressive bilateral
      sensorineural hearing loss caused by otosclerosis, restricted to the cochlea. The
      characteristics of the clinical course include: 1. Bilateral asymmetric
      sensorineural hearing loss. 2. Roaring tinnitus. 3. Episodes of sudden hearing
      loss. 4. Excellent response to prednisolone therapy. 5. In the late stage of the
      disease a small but transitory conductive hearing loss. High resolution computed
      tomography in such cases reveals diffuse osteolytic foci within the cochlear
      walls. In severe cases of such progressive deafness we discuss an
      antiproliferative (immunosuppressive) therapy with cyclosporine and/or a
      radionuclide therapy with Sn-117 m, an isotope with a very small irradiation
      radius.

PMID- 10080124
TI  - [Genetic predisposition for the development of head and neck carcinomas].
AB  - BACKGROUND: While cigarette smoking and chronic alcohol consumption are the major
      risk factors for the development of head and neck cancer, it is assumed that
      genetic factors contribute to risk. Glutathione-S-transferase GSTM1 AB, GSTM3 BB
      and GSTP1 AA as well as TNF genotypes were determined from leucocyte DNA in 392
      patients with head and neck carcinoma and 216 controls, with added
      immunohistochemical studies. Comparative genomic hybridization was used to screen
      for genetic alterations in the tumor tissue. RESULTS: While the frequency of
      GSTM1 AB was significantly lower in all head and neck carcinomas compared with
      controls, GSTM3 BB was significantly lower in the laryngeal and GSTP1 AA in the
      oral cavity/pharyngeal carcinoma cases; the frequency of the TNFb3 allele was
      higher in the laryngeal cases. Chromosomal alterations were specific for head and
      neck carcinomas, differing both in well differentiated and undifferentiated and
      in metastasizing and non-metastasizing tumors. CONCLUSIONS: Allelism at GST gene
      loci mediates susceptibility to head and neck carcinomas: GSTM1 AB is associated
      with a lower risk for all head and neck carcinomas, GSTM3 BB only for laryngeal
      carcinomas and GSTP1 AA only for oral cavity/pharyngeal carcinomas. The TNFb3
      allele was significantly more frequent in laryngeal cancer patients. The genetic
      alterations in the tumor tissue are in line with the "tumor progression model".
      Genetic conditions are important from the first exposure with carcinogens up to
      late genetic events in the tumor tissue.

PMID- 10080125
TI  - [Improvements in intra-arterial chemotherapy].
AB  - BACKGROUND: Intraarterial (i.a.) chemotherapy of head and neck cancer is a
      worldwide field of clinical research which is still developing. Over the last
      decade several improvements have been made. This paper relates our own
      experiences with the so-called bypass method of i.a. chemotherapy and with some
      recent international developments. METHODS: Between 1989 and 1998, 28 patients
      with head and neck cancer received Cisplatin intraarterially via the bypass
      route, 24 of them with a curative intention without any pretreatment. The daily
      dose was 20 mg and the overall aspired dosage was about 400 mg, given over a
      period of about 5 weeks, followed by full dose irradiation (> 60 Gy). During
      these 5 weeks anticoagulation with warfarin was performed. RESULTS: 16 patients
      received the planned total dose of i.a. Cisplatin. Ten cases of non-life
      threatening bone marrow depression and/or 7 cases of slight kidney insufficiency
      led to premature termination of the chemotherapy. Due to anticoagulation no
      technical failures occurred (early thrombosis of the cannulated artery), as we
      had experienced in the past. In 12 of 24 cases a complete remission was observed.
      CONCLUSION: The bypass method is a technically well-developed method of i.a.
      infusion if performed by experienced personnel.

PMID- 10080126
TI  - [In search of new treatment methods for head-neck carcinoma].
AB  - During the past decades the clinical prognosis of head and neck squamous cell
      cancer has remained unchanged. This indicates that new therapeutic strategies are
      needed. Cancer prevention strategies focusing on the elimination of carcinogenic
      substances could help to lower the incidence of this disease. Documentation of
      the clinical outcome in tumor registers could help to establish a better
      understanding of tumor biology and adequate treatment of different tumor types.
      Nevertheless the most promising approach at the current time seems to be the
      development of new immunotherapeutic treatment regiments. One possible way of
      future cancer treatment could be the application of bispecific antibodies that
      redirect immune effector cells to the tumor. A second approach could be in vivo
      gene therapy with direct intratumoral injections of a gene coding for interleukin
      2. This should help to reactivate tumor-suppressed immune effector cells.

PMID- 10080127
TI  - [Induction of antitumor immune response in the mouse model after vaccination with
      B7.1 expressing tumor cells].
AB  - The aim of the study was the induction of an antitumor immune response by genetic
      modification of tumor cells. This was done by transfecting the costimulatory
      molecule B7.1 into a murine tumor cell line SCCVII/SF in order to increase T cell
      recognition and to install an immunologic memory. One cohort of immunocompetent
      mice C3 H/HeN were injected with B7.1 expressing tumor cells, while the control
      group received parental B7.1 negative tumor cells. In a second step those
      immunized mice were rechallenged by parental tumor cells and tumor growth was
      compared to a new control group. Transfection with B7.1 prohibits outgrowth of
      the SCCVII cell line. Animals that have been vaccinated in this way are partially
      immune towards a secondary exposition to B7.1 negative tumor cells. Outgrowth of
      this recurrent tumor is slowed down. Such an immunization builds up an
      immunologic memory. Vaccination with B7.1 expressing tumor cells lead to a
      partial protective tumor immunity in the SCCVII-C3 H/HeN mouse model.

PMID- 10080128
TI  - [Navigation surgery in diseases of the paranasal sinuses].
AB  - BACKGROUND: Since the mid-80s, endonasal sinus surgery has gained significant
      importance in the treatment of chronic inflammatory sinus disease. Many surgeons
      have recognized the necessity of developing new methods to increase the safety of
      this type of surgery. One of the advancements in increasing the safety of
      endonasal sinus surgery was the development of computer-aided surgical navigation
      (CAS) systems. METHODS: Since 1996, we have tried several different CAS systems
      for difficult surgical procedures in sinus and anterior skull base surgery,
      mainly revision surgery for chronic inflammatory sinusitis and endonasal tumors.
      During this time, we tried one electromagnetic ("Insta Trak") and two
      optoelectric systems ("Surgigate" and "Vector Vision"). RESULTS: In our
      experience, all systems can be used in endonasal sinus surgery; accuracy was
      satisfactory and varied between 0.1 and 0.5 mm. There were differences with
      respect to the time of preparation of the system for surgery as well as to the
      possibility to use different instruments. CONCLUSIONS: Computer-assisted surgical
      navigation systems today have gained a degree of accuracy which makes them not
      only suitable but almost necessary, at least for difficult surgical procedures at
      the anterior skull base, i.e. revision surgery in chronic inflammatory sinus
      disease. On the long run, these systems will become mandatory for these kinds of
      procedures. On the other hand, CAS systems cannot substitute thorough anatomical
      and surgical training.

PMID- 10080129
TI  - [Mycoses of the paranasal sinus system].
AB  - BACKGROUND: During the last few years, in increasing number of fungal infections
      in the paranasal sinus system has been observed. Aspergillus species as well as
      mucor and candida albicans are especially responsible for these mycoses.
      PATIENTS: Twenty-seven cases of a fungal infection of the paranasal sinuses were
      observed between 1986 and 1997. The majority of the patients showed a chronic
      noninvasive form with affection of the maxillary sinus. Other forms (fulminant
      invasive form, chronic invasive form, allergic fungal sinusitis) are described.
      Typical features for fungal infection do exist in MRI and CT. CONCLUSIONS: A
      flexible therapeutic strategy is required in which appropriate pharmacologic and
      surgical options are tailored to the respective clinical picture.

PMID- 10080130
TI  - [Laser surgery of the middle nasal meatus in recurrent sinusitis].
AB  - We present our concept for treating patients suffering from recurrent sinusitis
      with coagulating lasers (Nd:YAG 1024 nm, Diode 810 or 904 nm). In these patients,
      the middle meatus is often narrowed by a hyperplastic middle turbinate, septum
      spurs and ridges, or by isolated polyps that block an ostium. We treat these
      patients by linear or punctate coagulation of the lateral wall of the middle
      turbinate, reducing the size of septum spurs, and blunting septal ridges or
      coagulating polyps. The outpatient procedure is performed with a laser fiberoptic
      system of 400 nm in contact mode with an energy of 3-5 watts. The amount of total
      energy applied to a specific tissue depends on the duration of laser contact at
      that point. The patient is anaesthesized superficially. Patients with a high
      degree of nasal hyperreactivity also receive antihistaminic preoperative
      treatment. Initial results show a significant increase of nasal flow with a
      decrease of sinus symptoms.

PMID- 10080131
TI  - [Tracheal reconstruction with preserved tracheal homograft--new aspects].
AB  - BACKGROUND: The treatment of long-segment tracheal stenosis is a biological and
      surgical problem. The introduction of preserved allografts established new
      possibilities for functional tracheal reconstruction. PATIENTS AND METHODS: Since
      1979 preserved allografts were used in 112 patients (including 20 children) with
      tracheal stenosis. Increasing knowledge in preservation, surgical treatment and
      pathohistology were put into practice. RESULTS: Implantation of the preserved
      allografts into the infrahyoid muscles proved to be advantageous. Preservation
      with the tutoplast method prevented the risk of viral infection, and led to
      faster and trouble-free post-operative healing. Pathohistological studies let to
      improve surgical techniques by increasing the knowledge of the nature of tracheal
      stenosis. CONCLUSION: Functional tracheal reconstruction for long-segment
      tracheal stenosis can be achieved by implantation of preserved allografts.

PMID- 10080132
TI  - [Interesting case no. 20--corpus alienum colli].
AB  - We report about a 39-year-old man who presented at the department of ENT Wurzburg
      suffering from a suspicious abscess or tumor of the right neck. Computed
      tomography and X-ray of the neck did not clarify the entity of the process
      sufficiently. The emergency surgical exploration of the neck showed an unexpected
      result: a compress which was forgotten during strumectomy 20 years ago.

PMID- 10080133
TI  - [Surgery of the cervical lymph system, II].

PMID- 10080134
TI  - Squamous cell papillomatosis of esophagus following placement of a self-expanding
      metal stent.
AB  - The esophageal self-expanding metal stent has gained widespread acceptance for
      the management of tracheoesophageal fistulas and the palliative management of
      malignant esophageal strictures. The complications associated with its use can be
      classified as either immediate or delayed. The most frequent delayed
      complications include tumor ingrowth, stent migration, reflux of gastric
      contents, bleeding, and perforation. This case report illustrates an otherwise
      unrecognized delayed complication of a self-expanding metal stent. Near complete
      ingrowth of the stent by squamous mucosal hyperplasia occurred within six weeks
      of the metal stent's placement. This finding supports the hypothesis that mucosal
      injury and regeneration underlies the etiology of esophageal squamous cell
      papilloma formation.

PMID- 10080135
TI  - Osmotic effect of honey on growth and viability of Helicobacter pylori.
AB  - Honey from New Zealand and Saudi Arabia at concentrations approximating 20% (v/v)
      inhibit the growth of H. pylori in vitro. The anti-H. pylori effect involves both
      hydrogen peroxide- and non-peroxide-mediated killing mechanisms. This study was
      designed to determine whether the anti-H. pylori activity of honey differed
      regionally (honey from Texas, Iowa, and New Zealand) and to determine whether
      this activity was due to the presence of hydrogen peroxide. Broth dilution
      susceptibility tests were performed using solutions of honey prepared in BHI
      broth ranging in concentration from 5 to 35% (v/v) in 5% increments. Control
      solutions containing glucose, fructose, and combined glucose/fructose solutions
      in ratios of 1:1.23 were also prepared. Paired catalase controls were included in
      all tests. Twenty-eight clinical isolates of H. pylori were tested. Growth was
      determined on the basis of a plus/minus grading score. All of the solutions
      containing either fructose, glucose, glucose and fructose combinations, or honey
      were equally effective in inhibiting the growth of H. pylori. All of the isolates
      were inhibited by solutions containing 15% (w/v) carbohydrate. Honey solutions,
      with or without catalase, inhibited 24/28 isolates at a concentration of 10%, and
      28/28 isolates at a concentration of 15%. In conclusion, regional differences in
      honey activity against H. pylori were not detected, nor was the effect of killing
      related to the presence of hydrogen peroxide in the honey samples. Osmotic
      effects were shown to be the most important parameter for killing H. pylori as
      all carbohydrate solutions > or = 15% (v/v) inhibited 100% of the H. pylori.

PMID- 10080136
TI  - Apoptosis in Helicobacter pylori-associated gastric and duodenal ulcer disease is
      mediated via the Fas antigen pathway.
AB  - Increased mucosal apoptosis is seen in H. pylori-infected gastric tissue;
      however, the precise mechanism by which this organism triggers programmed cell
      death is poorly understood and is investigated in this study. One pathway for
      induction of apoptosis is the Fas Ag pathway. Normal gastric and small bowel
      tissue express low levels of Fas antigen and nondetectable levels of Fas ligand.
      Consequent to H. pylori infection, there is elevated expression of Fas antigen in
      mucosal cells concurrent with Fas ligand expressing lymphocytes. This prompted us
      to investigate the potential role of Fas in mediating H. pylori-related
      apoptosis. It has been shown that inflammatory cytokines are abundant in H.
      pylori-infected tissue and that cytokines regulate the expression of Fas Ag in
      various tissue types. Using cell culture, we examine the role of specific
      inflammatory cytokines in activating this pathway. This communication presents
      the first evidence to implicate the Fas pathway in mediating apoptosis in H.
      pylori-associated gastric and duodenal ulcer disease.

PMID- 10080137
TI  - Helicobacter pylori in dental plaque: a comparison of different PCR primer sets.
AB  - This study was designed to compare different primer sets for PCR analysis of H.
      pylori in the same series of 40 dental plaque samples. Three pairs of primers,
      HPU1/HPU2, HP1/HP2, and EHC-U/EHC-L, directed to the urease A gene, 16S rRNA
      gene, or 860-bp DNA of H. pylori, respectively, were used. Our results
      demonstrate that EHC-L/EHC-U were more specific and sensitive for H. pylori added
      to saliva or dental plaque than HPU1/HPU2 and HP1/HP2. The detection rates for H.
      pylori DNA in dental plaque samples from randomly selected adult patients from
      the Dental Clinic of the University of Ulm were 26.5% (9/34) for HPU1/HPU2, 78.9%
      (30/38) for HP1/HP2, and 100% (40/40) for EHC-U/EHC-L (P < 0.001). Nested PCR
      using primers directed to the 860-bp DNA of H. pylori further confirmed the
      presence of H. pylori DNA (40/40) in all these samples. Our results indicate that
      primers EHC-U/EHC-L are to be recommended for PCR detection of H. pylori in the
      oral cavity.

PMID- 10080138
TI  - No evidence for an association between H. pylori and idiopathic chronic
      urticaria.

PMID- 10080139
TI  - Relationship of Helicobacter pylori CagA status to gastric cell proliferation and
      apoptosis.
AB  - Despite the fact that the association of Helicobacter pylori with an increased
      risk of gastric cancer is well documented, the exact mechanisms of this
      association have not been elucidated. Our aim was to shed some light on these
      mechanisms by studying the relationship of H. pylori CagA status to gastric cell
      proliferation and apoptosis, since both play an important role in
      gastrointestinal epithelial cell turnover and carcinogenesis. We studied fifty
      patients [32 men, 18 women, median age 39.5 years (range 18-67)], referred for
      upper gastrointestinal endoscopy, from whom antral biopsies were taken. On biopsy
      specimens gastritis was estimated by scoring the severity of inflammatory
      infiltrate, and the presence of atrophy and intestinal metaplasia were also
      noted. The gastric cell proliferation index (PI) was estimated by AgNOR staining,
      the epithelial apoptotic index (AI) was measured by special staining for
      apoptosis, and CagA status was determined serologically by immunoblotting the
      sera of patients against H. pylori antigens. Thirty-eight (76%) of the 50
      patients were H. pylori (positive) and 12 (24%) H. pylori (negative). Among the
      38 H. pylori(+) patients, 28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the
      H. pylori CagA(+) and CagA(-) groups, the PI values [median (ranges)] were 5 (4
      7) and 3.7 (3.5-5.5), respectively (P < 0.05). In addition the difference in PI
      between the H. pylori CagA(+) and H. pylori(-) groups was highly significant (P <
      0.001). Concerning apoptosis, in the H. pylori CagA(+) and CagA(-) groups, the
      values for AI were 1 (1-30) and 5.5 (1-35), respectively (P < 0.05). In addition,
      the difference in AI between the H. pylori CagA(-) and H. pylori(-) groups, was
      significant (P < 0.05). We conclude that H. pylori CagA(+) strains induce
      increased gastric cell proliferation, which is not accompanied by a parallel
      increase in apoptosis. This might explain the increased risk for gastric
      carcinoma that is associated with infection by H. pylori CagA(+) strains.

PMID- 10080140
TI  - The role of phospholipase A2 in calcium-ionophore-mediated injury to rat gastric
      mucosal cells.
AB  - Although transient increases in intracellular Ca2+ ([Ca2+]i) underlie a number of
      important physiological processes, sustained elevations in [Ca2+]i mediate damage
      to a number of tissues and cell types including gastric mucosal cells. Increases
      in [Ca2+]i can activate phospholipid hydrolysis via increases in phospholipase A2
      (PLA2) activity and subsequent cell injury. In the present study we have examined
      whether [Ca2+]i-induced gastric cellular injury is mediated by PLA2 activation.
      Gastric mucosal cells were harvested from rat stomachs after pronase digestion.
      Cell integrity was assessed using trypan blue dye exclusion and release of
      lysozomal enzymes. PLA2 activity was estimated colorimetrically by determination
      of thiol release from the substrate, arachidonyl thio-PC. In these studies
      calcium ionophore A23187 (3-25 microM) resulted in an increase in cell injury.
      The damage produced by A23187 (12.5 microM) was inhibited by preincubation of
      cells with the PLA2 inhibitor, quinacrine (1-100 microM). Quinacrine did not
      reduce ethanol (10% w/v) mediated-cell damage. Similarly Ca2+ ionophore A23187
      treatment resulted in a concentration-dependent increase in PLA2 activity in
      gastric cells. The increase in PLA2 activity was attenuated if cells were
      incubated in Ca2+-depleted medium containing EGTA (4 mM). Furthermore
      lysophospholipids generated by PLA2 (lysophosphatidylethanolamine and
      lysophosphatidylcholine; 100 microM) also increased the degree of cell injury.
      Pretreatment of cells with the PAF antagonist WEB 2086 (10(-6) and 10(-5) M), the
      leukotriene synthase inhibitor 5,6-dehydroarachidonic acid (10 microM), or the
      thromboxane synthase inhibitor furegrelate (1 microM) decrease A23187-mediated
      cell injury. These data suggest that Ca2+ ionophore-mediated increases in [Ca2+]i
      result in gastric cell injury and this effect is mediated in part by PLA2
      activation and subsequent release of free fatty acids and lysophosphatides.

PMID- 10080141
TI  - Protective effect of a vasopressin-1 selective antagonist, OPC-21268, against
      ethanol-induced damage of the rat gastric wall.
AB  - Since endogenous vasopressin has been reported to be an aggressor in the gastric
      mucosa and a vasoconstrictor in the gastric circulation, we investigated the
      gastric cytoprotective effects of OPC-21268, a newly developed, nonpeptide,
      orally active vasopressin-1 receptor antagonist, on ethanol-induced gastric
      injury in rats. The rats were treated with OPC-21268 or placebo 2 hr before
      ethanol administration, and the gastric mucosa was evaluated macroscopically for
      ulcer damage, and histologically for gastric mucosal injury. Gastric mucosal
      blood flow, erythrocyte volume, and erythrocyte velocity were also measured in
      groups given saline, ethanol alone, and ethanol after OPC-21268. To investigate
      the role of systemic or locally secreted vasopressin, we measured plasma and
      tissue (gastric mucosa) vasopressin concentrations after ethanol or vehicle
      administration. Prophylactic OPC-21268 treatment improved the gastric ulcer score
      in a dose-dependent manner, and histological examination demonstrated that the
      drug significantly ameliorated the gastric injury induced by ethanol. The
      hemodynamic values obtained in the OPC-21268-treated and ethanol-treated group
      were similar to those in the saline control group, but values were significantly
      (P < 0.05) higher for gastric mucosal blood flow and erythrocyte velocity and
      lower for erythrocyte volume compared to the group given ethanol alone. Plasma
      vasopressin concentrations were not significantly different in the control group
      and at 15, 30, and 60 min after administration of ethanol. However, ethanol
      administration caused a threefold increase in gastric tissue vasopressin level (P
      < 0.05) compared to the control group. These results suggested that OPC-21268
      relieved congestive hyperemia in the gastric mucosa and ameliorated the mucosal
      injury caused by ethanol, probably as a result of inhibition of vasopressin
      mediated actions on the stomach. The vasopressin involved was probably generated
      locally in the gastric mucosa after ethanol administration.

PMID- 10080142
TI  - Suppression of ethanol-induced apoptotic DNA fragmentation by
      geranylgeranylacetone in cultured guinea pig gastric mucosal cells.
AB  - The purpose of this study was to elucidate the molecular mechanism of action of
      geranylgeranylacetone, an antiulcer drug. Treatment with ethanol for 8 hr at the
      optimum concentration (7.5%) caused apoptotic DNA fragmentation in cultured
      guinea pig gastric mucosal cells. Pretreatment of cells with
      geranylgeranylacetone suppressed the DNA fragmentation in a dose-dependent
      manner. The maximum effect was achieved at 10(-6) M, at which concentration the
      drug was previously shown to induce heat-shock proteins. The suppression required
      an incubation period longer than 1 hr. Pretreatment of cells with low
      concentrations of ethanol also prevented DNA fragmentation.

PMID- 10080143
TI  - Luminal calcium in regulation of nitric oxide release and acid secretion in rat
      stomachs after damage.
AB  - We investigated the role of luminal Ca2+ in the regulation of nitric oxide (NO)
      release and acid secretion in the rat stomach following damage by sodium
      taurocholate (TC). Under urethane anesthesia, a rat stomach was mounted in an ex
      vivo chamber, perfused with saline, and transmucosal potential difference (PD),
      luminal pH, acid secretion, and luminal contents of Ca2+ and NO were measured
      before and after exposure to 20 mM TC for 30 min, with or without coapplication
      of EGTA (5 mM) and/or CaCl2 (10 mM). Mucosal exposure to TC caused a reduction in
      PD and a decrease of acid secretion, with a concomitant increase of NO as well as
      Ca2+ content in the gastric lumen. The increase of NO release as well as the
      reduced acid response were attenuated by pretreatment with L-NAME or
      coapplication of EGTA, and the latter inhibited the luminal increase of Ca2+. The
      changes caused by L-NAME were antagonized by coadministration of L-arginine,
      while those induced by EGTA were partially antagonized by coinstillation of
      CaCl2. Neither treatment tested had any effect on gastric PD responses to TC.
      These results suggest that: (1) damage in the stomach increases the release of
      Ca2+ as well as NO in the lumen; (2) acid secretion decreases in response to
      damage by both an NO- and Ca2+-dependent mechanism; and (3) the increase of
      luminal Ca2+ is an adaptive response of the stomach to damage and may play an
      important role in increasing NO production and hence in regulating acid
      secretion.

PMID- 10080144
TI  - Dynamics of level of randomness of electrogastrograms can be indicative of
      gastric electrical uncoupling in dogs.
AB  - Gastric electrical uncoupling is the lack of electrical synchronization in
      different parts of the stomach. The aim of this study was to investigate the
      impact of gastric electrical uncoupling on the level of randomness of canine
      electrogastrograms (EGG). Electrogastrograms were obtained from 11 unconscious
      acute dogs. Gastric electrical uncoupling was produced surgically by performing
      two consecutive circumferential cuts through the entire thickness of the gastric
      muscle layer. Three separate 1/2-hr eight-channel bipolar EGGs were obtained from
      each dog in the basal state and after each cut. The signals were amplified using
      amplifiers with a flexible frequency range, digitized with 10-Hz sampling
      frequency, and 4.27-min portions of the digital EGGs were subjected to a turning
      point test for randomness. The number of turning points (NTPs) was determined
      from successive time intervals calculated from all EGG channels. Distributions of
      NTPs were calculated for each dog. An average NTPs (ANTP) for each dog in a given
      state (basal, after the first cut, and after the second cut) was calculated from
      the ANTPs of all channels. In six of 11 dogs the ANTP were greater after the
      first cut. The number rose to nine of 11 dogs after the second cut. In only 45%
      of the dogs were the ANTP distributions significantly different (P < 0.01) after
      the first cut (sensitivity 45%). After the second cut the sensitivity rose to
      64%. In two specific EGG channels NTP distribution was significantly different (P
      < 0.01) in nine of 11 dogs (sensitivity: 82%) after the second cut. The dynamics
      of the level of randomness in EGG can be indicative of severe gastric electrical
      uncoupling. Some EGG channel configurations are more sensitive than others in
      recognizing gastric electrical uncoupling.

PMID- 10080145
TI  - Esophageal swallowing phase assessed by audiosignal recording: relationship with
      manometry in gastroesophageal reflux disease patients.
AB  - The acoustic technique has been used for pharyngeal exploration but to date no
      such technique has been devised to assess esophageal motility. The aim of this
      study was to demonstrate that displacement through the esophagus can be
      quantified using this method in healthy subjects and in patients with
      gastroesophageal reflux. Concurrent manometric and acoustic recordings were also
      performed in the patients. Fifteen controls (38.5 +/- 13 years old) and 10
      patients (34.9 +/- 6 years old) were included. All were recorded during wet and
      dry swallow sequences with microphones placed below the cricoid cartilage and on
      the xiphoid appendix. Standard manometry was performed for lower esophageal
      sphincter (LES) exploration. For the acoustic technique, the frequency of xiphoid
      signals (FX), esophageal transit time (ETT), duration of xiphoid sound (SD), and
      for the manometric study, the duration of LES relaxation (RD) were recorded and
      mean values were calculated (FXm), (ETTm), (SDm), (RDm). FXm for wet (94 vs
      81.6%) and dry swallows (86 vs 66.6%) decreased in patients. ETTm was
      significantly higher (P < 0.01) for wet than for dry swallows (5.6 +/- 0.9 vs 5.2
      +/- 1.2 sec) for controls but not for patients. ETTm was significantly higher for
      patients for wet (7.2 +/- 2.1 sec) and for dry swallows (6.5 +/- 2.3 sec) than
      for controls and SDm was lower. Xiphoid sound appeared in the second half of LES
      relaxation. Our noninvasive acoustic technique is simple and reproducible. It is
      well correlated with manometry, and it allows characterization of the
      displacement of the bolus through the esophagus and the LES. The technique could
      be used alone to determine appropriate pharmacological and surgical treatments
      for esophageal motility disorders.

PMID- 10080146
TI  - Achalasia: the usefulness of manometry for evaluation of treatment.
AB  - Although manometry is used with increasing frequency to evaluate the
      effectiveness of different treatments for achalasia, the criteria for a
      successful manometric response have not been well defined. Manometric responses
      were collected before and after 43 treatments in 35 patients with achalasia in
      order to determine manometric changes after different clinical outcomes: 15
      unsuccessful outcomes and 28 successful outcomes were reported. In the latter,
      resting pressure of the lower esophageal sphincter decreased to 12.8 mm Hg,
      whereas in unsuccessful outcomes this was significantly higher (28.2 mm Hg). A
      decrease of lower esophageal sphincter pressure below 17 mm Hg or more than 40%
      of the pretreatment level was associated with successful outcomes. Our data
      suggest that manometry is a good indicator of therapeutic effectiveness and we
      propose that it be used systematically for objective evaluation of achalasia
      treatment.

PMID- 10080147
TI  - Bacteribilia and cholangitis after percutaneous transhepatic biliary drainage for
      malignant biliary obstruction.
AB  - Cholangitis often develops after percutaneous transhepatic biliary drainage
      (PTBD) for malignancy. The aims of this retrospective study were to clarify
      whether or not bacteribilia and cholangitis increase with time after PTBD and to
      define the pathogenesis of bacteribilia and cholangitis after PTBD. One hundred
      twenty-eight patients underwent PTBD for malignancy. Both the cumulative
      incidences of bacteribilia (77%) and cholangitis (28%) showed an increase with
      time after PTBD. In 78% of patients with bacteribilia, bacteria from intestinal
      flora were detected in bile. Catheter malfunction (N = 17) or the presence of
      undrained bile ducts (N = 7) induced cholangitis. Proximal obstruction, because
      it often accompanied undrained ducts, had higher incidences of bacteribilia (P =
      0.04) and cholangitis (P < 0.0001) than did distal obstruction. In conclusion,
      bacteribilia and cholangitis increase in incidence with time after PTBD. The
      primary cause of bacteribilia is the transpapillary reflux of intestinal flora.
      Catheter malfunction or undrained ducts cause cholangitis, provided underlying
      bacteribilia is present.

PMID- 10080148
TI  - Nonfunctioning islet cell tumor with a unique pattern of tumor growth.

PMID- 10080149
TI  - Preoperative histological diagnosis of heterotopic pancreas.

PMID- 10080150
TI  - Reduction in hMSH2 mRNA levels by premature translation termination: implications
      for mutation screening in hereditary nonpolyposis colorectal cancer.
AB  - We have used single-strand conformational polymorphism (SSCP) and heteroduplex
      analysis to examine DNA from 50 colorectal carcinoma patients coming from
      families meeting the Amsterdam criteria for hereditary nonpolyposis colorectal
      cancer (HNPCC) or having developed colorectal carcinoma at age 45 or younger. We
      identified mutations in 12 of these patients, with seven of these being novel
      mutations. We examined four of the truncating mutations using in vitro
      transcription and translation (IVTT) assays and determined that the mutation
      causing an in-frame deletion of exon 5 could easily be detected by the IVTT
      assay, but the three mutations resulting in premature translation termination
      were not detected because the steady-state levels of the mutant allele
      transcripts are too low. Our findings suggest that some but not all mutant hMSH2
      alleles have significantly lower steady-state mRNA levels than the normal allele.
      Under ideal circumstances, where lymphoblastoid cell lines are available for RNA
      extraction, IVTT may be useful for detecting truncating mutations. However, our
      data suggest that caution should be taken in using IVTT in routine screening of
      clinical samples for truncating HNPCC mutations, as many mutations may go
      undetected.

PMID- 10080151
TI  - Iron chelator deferoxamine reduces preneoplastic lesions in liver induced by
      choline-deficient L-amino acid-defined diet in rats.
AB  - The aim of this study was to investigate whether an iron chelator, deferoxamine
      (DFO) can prevent lipid peroxidation, resulting in reduced liver injury as well
      as reducing preneoplastic lesions induced by a choline-deficient L-amino acid
      defined (CDAA) diet. CDAA diet administration resulted in an increased serum ALT
      level (367 +/- 58) after two weeks, but simultaneous DFO treatment for two weeks
      reduced this elevation of ALT as well as malondialdehyde (MDA) production in the
      liver. Feeding rats a CDAA diet for 12 weeks led to the development of severe
      liver fibrosis and preneoplastic lesions detected as enzyme-altered lesions. DFO
      treatment prevented the expression of activated stellate cells, resulting in the
      reduction of liver fibrosis as well as reducing the development of preneoplastic
      lesions. These results indicate that iron chelation can reduce the development of
      preneoplastic lesions in a CDAA diet model.

PMID- 10080152
TI  - Clinical forms of human Schistosoma mansoni infection are associated with
      differential activation of T-cell subsets and costimulatory molecules.
AB  - The current study has compared the activation status and the expression of the
      CD28 molecule on circulating CD4+ and CD8+ lymphocytes from patients with
      different clinical forms of schistosomiasis. The data show that patients with
      acute schistosomiasis have an increase on the mean percentage of CD4+ HLA-DR+
      cells, whereas chronic asymptomatic patients exhibit an increased mean percentage
      of CD8+ HLA-DR+ cells. Patients with the hepatosplenic disease showed an increase
      in both CD4+ HLA-DR+ and CD8+ HLA-DR+ cells. Despite the high levels of CD8+ HLA
      DR+ cells in hepatosplenic patients, they presented a decreased ratio of CD8+
      CD28+/CD8+ cells. These findings of a different percentage of circulating CD8+
      CD28+ cells might explain the different in vitro cellular reactivity of
      asymptomatic and hepatosplenic patients and the defects in the cytokine secretion
      patterns reported in individuals with hepatosplenic schistosomiasis.

PMID- 10080153
TI  - A colon-derived inflammatory pseudotumor.

PMID- 10080154
TI  - Surgical correction of patent ductus venosus in three brothers.
AB  - We report the presence of a patent ductus venosus in three brothers who underwent
      surgical correction. Patent ductus venosus was demonstrated by ultrasonography.
      Portosystemic venous shunt ratios as evaluated by [123I]iodoamphetamine per
      rectal portal scintigraphy were 67%, 50%, and 77%, respectively. Histologic
      examination of liver biopsy specimens revealed fatty degeneration in all cases.
      Portal vein pressure before and after temporarily occluding the patent ductus
      venosus was estimated by an Anthron P-U catheter introduced into the portal vein
      via the ligament teres hepatis. Portal venous pressure increased from 10 to 17 cm
      H2O, 16 to 23 cm H2O, and 14 to 27 cm H2O, respectively. Therefore, banding of
      the ductus venosus with Teflon tape was attempted to prevent portal hypertension
      following complete ligation. As a result, portal venous pressures after stricture
      of the ductus venosus were 12, 21, and 20 cm H2), respectively. Bile acid and
      liver enzymes decreased and returned to normal within 14 days after surgery.
      Interestingly, serum concentrations of hepatocyte growth factor (HGF) increased
      significantly after restoration of the portal blood flow and then gradually
      decreased, but remained persistently elevated for at least two weeks in two cases
      measured after surgical correction. One month after correction, liver function
      returned to normal as assessed by serological and histological parameters in all
      cases. These results suggest that it is important to determine whether stricture
      or complete ligation is indicated for a patent ductus venosus during surgical
      correction, based on the portal venous pressure after temporal test occlusion of
      the duct. In addition, HGF may be a useful marker for normalization of hepatic
      microcirculation after surgery.

PMID- 10080155
TI  - Clinical significance of hepatic dysfunction with jaundice in typhoid fever.
AB  - A retrospective case note review was undertaken to assess the clinical
      significance of hepatic dysfunction with jaundice in typhoid fever. Of the 57
      patients, 21 (36.8%) had jaundice, while 36 (63.2%) did not have jaundice.
      Significantly higher proportions of jaundiced patients were females (P = 0.04).
      Confusion (P = 0.01), upper abdominal pain (P = 0.02), right upper quadrant
      tenderness (P = 0.0001), and low prothrombin index (P = 0.04) were statistically
      significant occurrences in jaundiced patients on admission. Admission mean values
      of serum bilirubin (P = 0.0001), gamma-glutamyltranspeptidase (GGT; P = 0.009),
      and alanine aminotransferase (ALT; P = 0.0005) were significantly higher in
      icteric patients while mean values of total serum protein (P = 0.0009) and
      albumin (P = 0.0001) were significantly higher in anicteric patients. There were
      no deaths. Glomerulonephritis occurred significantly (P = 0.001) more frequently
      in icteric patients. It is concluded that hepatic dysfunction with jaundice in
      typhoid fever indicates more severe hepatic injury, which may precipitate the
      development of clinically detectable glomerulonephritis.

PMID- 10080156
TI  - Microsatellite instability is absent in liver and biliary mucosa of patients with
      primary sclerosing cholangitis.
AB  - Microsatellite instability occurs in the colonic mucosa of patients with
      inflammatory bowel disease and may predispose the mucosa to neoplastic
      transformation. It is unknown whether microsatellite instability also plays a
      role in the neoplastic risk associated with primary sclerosing cholangitis. We
      examined 134 tissue samples from 21 patients with sclerosing cholangitis for
      microsatellite instability at eight loci. All tissues were also stained
      immunohistochemically using an antibody to the proliferation marker Ki-67.
      Microsatellite instability did not occur in any samples from the intrahepatic or
      extrahepatic biliary system, although one patient demonstrated instability in the
      colon. Ki-67 indices ranged from 0 to 2.5 in nondysplastic biliary epithelium and
      from 1.5 to 29.4 in areas of dysplasia. The absence of microsatellite instability
      in sclerosing cholangitis suggests that the genetic basis of neoplastic
      progression in chronic inflammatory disease of the bile ducts differs from that
      of intestinal cancers arising in the setting of chronic inflammatory bowel
      disease and may relate to differences in the microenvironment in these two sites.

PMID- 10080157
TI  - Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study.
AB  - Currently, no accepted medical therapy for patients with primary sclerosing
      cholangitis (PSC) is available. Case-control studies have shown an inverse
      association between PSC and smoking behavior, suggesting that nicotine might have
      a beneficial effect in PSC. The aim of this study was to evaluate the safety and
      estimate the efficacy of oral nicotine in the treatment of PSC. Eight PSC
      patients who had never smoked received oral nicotine at a maximum dose of 6 mg
      four times a day for up to one year. Liver biochemistries and plasma cotinine
      levels were determined at entry and at three-month intervals during the study
      duration. Five patients completed one year of treatment, but three of them had to
      temporarily reduce the dose due to side effects. One patient completed only four
      months of treatment due to dizziness and heart palpitations. Two patients
      completed only one month of treatment due to reactivation of colitis requiring
      corticosteroid therapy. No significant changes in liver biochemistries were noted
      during the treatment period despite a significant increase in plasma cotinine
      levels. In conclusion, oral nicotine seems to have no beneficial effects in the
      treatment of PSC, and it is frequently associated with side effects necessitating
      permanent drug cessation.

PMID- 10080158
TI  - Differences between interferon-alpha and -beta treatment for patients with
      chronic hepatitis C virus infection.
AB  - To compare virological, biochemical, and immune responses to human lymphoblastoid
      interferon (IFN-alpha) and human fibroblast interferon (IFN-beta) in patients
      with chronic hepatitis C virus (HCV) infection, 120 patients were randomly
      assigned to three groups (group A, 60 patients receiving IFN-alpha, 6 million
      units (MU) once a day, daily for one month and thrice weekly for five months;
      group B, 40 patients receiving 6 MU IFN-beta once a day daily for two months; and
      group C, 20 patients receiving 3 MU IFN-beta twice a day (6 MU/day) daily for two
      months). Serum soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6)
      levels were measured by enzyme-linked immunosorbent assay. Patients with
      sustained clearance of serum HCV RNA detected by polymerase chain reaction (PCR)
      at six months after IFN treatment were defined as having complete response to IFN
      treatment. A low level of HCV RNA (< or = 10(4) copies/50 microl, measured by
      competitive PCR) and HCV RNA of genotype 2a were favorable factors for a complete
      response to both IFNs. Complete response in group A treatment was strongly
      associated with early HCV RNA clearance, in contrast with group B. A
      significantly higher HCV RNA negativity at the second week from start of
      treatment was noted in group C (80.0%), compared with groups A (41.6%) and B
      (27.5%). sIL-2R levels rose in each group during IFN administration. In group C,
      alanine aminotransferase (ALT) and IL-6 levels were remarkably elevated. These
      findings indicate that timing of serum HCV RNA negativity in sustained response
      differs between IFN-alpha and IFN-beta administrations and that early HCV RNA
      clearance was induced by twice-a-day IFN-beta treatment.

PMID- 10080159
TI  - Clinical course of chronic hepatitis C virus infection is not influenced by
      concurrent hepatitis G virus infection.
AB  - To determine the effects of hepatitis G virus (HGV) infection on chronic
      hepatitis C virus infection (HCV) and to evaluate HGV response to interferon, we
      investigated HGV RNA by polymerase chain reaction in 247 Japanese patients with
      chronic HCV infection (166 men and 81 women; 124 had chronic hepatitis and 26
      cirrhosis, and 97 hepatocellular carcinoma). HGV RNA was detectable in 22 (8.9%)
      patients, among whom 21 were men: this male predominance was statistically
      significant (P < 0.01). There were no differences in age, aminotransferase level,
      stage of liver disease, HCV RNA level by competitive polymerase chain reaction,
      genotype, or interferon response to HCV RNA between patients with HCV infection
      alone or with HCV/HGV coinfection. Sustained elimination of HGV RNA was found in
      28.6% of the 14 treated patients with HCV/HGV coinfection. In the 14 treated
      patients, sustained elimination of both viruses was seen in two, HCV alone was
      eliminated in two, and HGV alone was eliminated in two. Aminotransferase level
      improvement by interferon treatment was associated with clearance of HCV, but not
      of HGV. Thus, HGV infection had no apparent effects on HCV infection, and the
      sensitivity of HGV to interferon is comparable to but independent of HCV.

PMID- 10080160
TI  - Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of
      metalloproteinases -1 and -2 (TIMP-1 and TIMP-2) as noninvasive markers of liver
      disease in chronic hepatitis C: comparison using ROC analysis.
AB  - As chronic liver disease progresses, an imbalance occurs between synthesis and
      breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are
      involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs)
      prevent their fibrolytic action. We determined if plasma levels of MMP-2, TIMP-1
      and TIMP-2 are related to liver histology in patients with chronic hepatitis C.
      Plasma MMP-2, TIMP-1 and TIMP-2 levels were measured in 43 patients with chronic
      hepatitis C. Plasma levels of MMP-2, TIMP-1 and TIMP-2 and serum ALT were
      correlated with liver biopsy score and specificity and sensitivity of the assays
      in detecting advanced liver disease were calculated from ROC analysis. Plasma
      TIMP-1 was significantly correlated with histological activity index (r = 0.45),
      portal inflammation (r = 0.48), periportal necrosis (r = 0.34) and focal necrosis
      (r = 0.38). Plasma TIMP-2 was significantly correlated with fibrosis (r = 0.43)
      and confluent necrosis (r = 0.41). Using ROC analysis both TIMP-1 and TIMP-2 had
      significant diagnostic ability in detecting advanced liver disease (Area under
      the curve 0.73 for both, p 0.015 and 0.036 respectively). A normal plasma TIMP-1
      excluded advanced liver disease. Neither plasma MMP-2 or serum ALT were related
      to fibrosis or to histological activity index. With increased severity of liver
      disease in chronic hepatitis C there is increased plasma levels of TIMPs -1 and 
      2. Plasma TIMP-1 and TIMP-2 are sensitive and to a lesser extent specific in
      detecting advanced liver disease in chronic hepatitis C and could be used in
      preference to serum ALT.

PMID- 10080161
TI  - Visceral algesia in irritable bowel syndrome, fibromyalgia, and sphincter of oddi
      dysfunction, type III.
AB  - Visceral hyperalgesia has been demonstrated in patients with irritable bowel
      syndrome who are seen in tertiary care centers. It has been hypothesized that
      visceral hyperalgesia may be related to psychological distress associated with
      health care seeking behavior in these patients. Patients with fibromyalgia and
      sphincter of Oddi dysfunction, type III, share many demographic and psychosocial
      characteristics with patients with irritable bowel syndrome and provide an
      opportunity to test the hypothesis that rectal hyperalgesia is unique to IBS.
      Fifteen patients with IBS, 10 patients with fibromyalgia, 10 with sphincter of
      Oddi dysfunction, type III, and 12 controls underwent evaluation of rectal pain
      perception in response to phasic distensions and psychological testing with a
      self-report instrument. Patients with irritable bowel syndrome demonstrated
      significantly lower rectal pain thresholds and increased levels of psychologic
      distress compared to controls. Although sphincter of Oddi dysfunction patients
      also exhibited increased psychologic distress, rectal pain perception was similar
      to controls. Patients with fibromyalgia exhibited rectal algesia that was not
      significantly different from either controls or IBS. In conclusion, rectal
      hyperalgesia is not a function of chronic functional pain, health care seeking
      behavior, or psychological distress. However, it may not be specific for IBS.

PMID- 10080162
TI  - Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient
      with ulcerative colitis before and after antimicrobial treatments.
AB  - A 26-year-old female patient, suffering from recurrent attacks of ulcerative
      colitis accompanied by extraintestinal symptoms (erythema nodosum and pyoderma
      gangrenosum), was evaluated for the effect of antibacterial agents on the
      intestinal bacteria and their enzymatic activities. The enzymes were assayed both
      at the onset of disease symptoms and after treatment with each of five drug
      regimens (fluconazole and cefadroxil, cefuroxime axetil and cestriaxone sodium,
      ciprofloxacin and cestriaxone sodium, ciprofloxacin alone, and ciprofloxacin,
      metronidazole, and cephalexin). The activities of azoreductase, nitroreductase,
      oxidoreductase, glucuronidase, and sulfatase were generally lower following all
      of the treatments, especially when ciprofloxacin was included. The DNA from each
      sample was amplified by PCR, using random primers. Profiles of amplified DNA on
      agarose gels showed different patterns, indicating differences in the microflora
      before and after the antimicrobial treatments. The clinical response to
      antibacterial therapy was consistent with the decreased bacterial enzymatic
      activities and changes in the microbial population. Ciprofloxacin, which was
      associated with the most dramatic falls in enzymatic activity, also had the best
      clinical results. We conclude that intestinal bacteria and their enzymes play
      important roles in ulcerative colitis and that population changes can be
      monitored using PCR profiles.

PMID- 10080163
TI  - Characterization of two novel proabsorptive peptide YY analogs, BIM-43073D and
      BIM-43004C.
AB  - Effective clinical therapy to augment intestinal absorption of water and
      electrolytes does not exist; the gut hormone, peptide YY (PYY), is a potent
      proabsorptive agent in animal models. The purpose of our study was to evaluate
      the effects of two novel PYY analogs, BIM-43073D and BIM-43004C, on intestinal
      absorption. Dogs with ileal Thiry-Vella fistulae (TVF) were treated with either
      PYY, BIM-43073D, or BIM-43004C. Administration of BIM-43073D significantly
      increased water and sodium absorption over baseline and maintained this level of
      increased absorption for a longer duration than an equimolar dose of PYY.
      Administration of BIM-43004C significantly increased sodium and water absorption
      over baseline at a level equal to that of PYY. The novel PYY analogs, BIM-43073D
      and BIM-43004C, are effective proabsorptive agents with BIM-43073D producing more
      sustained effects than PYY. These compounds may be clinically useful in the
      treatment of gut malabsorption in conditions such as cholera, Crohn's disease,
      and the short-bowel syndrome.

PMID- 10080164
TI  - Interleukin (IL)-13 and IL-4 are potent inhibitors of IL-8 secretion by human
      intestinal epithelial cells.
AB  - Intestinal epithelial cells are able to produce soluble mediators that initiate
      or amplify inflammatory events in the intestinal mucosa. Interleukin (IL) -8 is
      suggested to be a cytokine playing a major role during the acute and chronic
      processes in inflammatory bowel disease (IBD). TH-2 cytokines have been described
      as down-regulating the inflammatory response. We analyzed the effects of IL-10,
      IL-13, and IL-4 on IL-8 secretion in intestinal epithelial cells. The human
      colonic epithelial cell line Caco-2 and freshly isolated intestinal epithelial
      cells were used. Cells were stimulated with IL-1beta after treatment with TH-2
      cytokines. Levels of IL-8 were determined by employing enzyme-linked
      immunosorbent assay (ELISA). Stimulation with IL-1beta results in a time
      dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to
      activated epithelial cells resulted in a strong decrease in IL-8 secretion.
      Maximal inhibition required that TH-2 cytokines be added up to 60 min before or
      simultaneous with stimulatory agents. We present novel findings that IL-4 and IL
      13 strongly down-regulate IL-8 secretion from intestinal epithelial cells. A
      microenvironment containing high concentrations of IL-4 and IL-13 may alter the
      recruitment of immune cells to enterocytes at least partly by inhibiting IL-8
      production. This inhibition might diminish the severity of the intestinal
      inflammatory response and, thus reduce clinical disease activity.

PMID- 10080165
TI  - DNA, not d.o.a.

PMID- 10080166
TI  - Redundancy reveals drugs in action.

PMID- 10080167
TI  - Is the genetic basis of DiGeorge syndrome in HAND?

PMID- 10080168
TI  - Excision repair invades the territory of mismatch repair.

PMID- 10080169
TI  - Modelling cancer in the mouse.

PMID- 10080170
TI  - Bumps and pumps, SERCA 1999.

PMID- 10080171
TI  - Birds on a wire and tiling the inner ear.

PMID- 10080172
TI  - An almost-intact human endogenous retrovirus K on human chromosome 7.

PMID- 10080173
TI  - 300 million years of conserved synteny between chicken Z and human chromosome 9.

PMID- 10080174
TI  - Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and
      myoclonic epilepsy.

PMID- 10080175
TI  - The insulin gene VNTR, type 2 diabetes and birth weight.

PMID- 10080176
TI  - Deafness linked to DFNA2: one locus but how many genes?

PMID- 10080177
TI  - RNA processing and the evolution of eukaryotes.
AB  - In eukaryotes, RNA processing events, including alternative splicing and RNA
      editing, can generate many different messages from a single gene. As a
      consequence, the RNA pool, which we refer to here as the 'ribotype', has a
      different information content from the genotype and can vary as circumstances
      change. The outcome of a single RNA processing event often regulates the outcome
      of another, giving rise to networks that affect the composition and expression of
      a particular ribotype. Successful ribotypes are determined by natural selection,
      and can be incorporated into the genome over time by reverse transcription.
      Eukaryotic evolution is therefore influenced by the alternate ways in which RNAs
      are processed and the continual interplay between RNA and DNA.

PMID- 10080178
TI  - Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.
AB  - Darier disease (DD) is an autosomal-dominant skin disorder characterized by loss
      of adhesion between epidermal cells (acantholysis) and abnormal keratinization.
      Recently we constructed a 2.4-Mb, P1-derived artificial chromosome contig
      spanning the DD candidate region on chromosome 12q23-24.1. After screening
      several genes that mapped to this region, we identified mutations in the ATP2A2
      gene, which encodes the sarco/endoplasmic reticulum Ca2(+)-ATPase type 2 isoform
      (SERCA2) and is highly expressed in keratinocytes. Thirteen mutations were
      identified, including frameshift deletions, in-frame deletions or insertions,
      splice-site mutations and non-conservative missense mutations in functional
      domains. Our results demonstrate that mutations in ATP2A2 cause DD and disclose a
      role for this pump in a Ca(2+)-signalling pathway regulating cell-to-cell
      adhesion and differentiation of the epidermis.

PMID- 10080179
TI  - Genomic profiling of drug sensitivities via induced haploinsufficiency.
AB  - Lowering the dosage of a single gene from two copies to one copy in diploid yeast
      results in a heterozygote that is sensitized to any drug that acts on the product
      of this gene. This haploinsufficient phenotype thereby identifies the gene
      product of the heterozygous locus as the likely drug target. We exploited this
      finding in a genomic approach to drug-target identification. Genome sequence
      information was used to generate molecularly tagged heterozygous yeast strains
      that were pooled, grown competitively in drug and analysed for drug sensitivity
      using high-density oligonucleotide arrays. Individual heterozygous strain
      analysis verified six known drug targets. Parallel analysis identified the known
      target and two hypersensitive loci in a mixed culture of 233 strains in the
      presence of the drug tunicamycin. Our discovery that both drug target and
      hypersensitive loci exhibit drug-induced haploinsufficiency may have important
      consequences in pharmacogenomics and variable drug toxicity observed in human
      populations.

PMID- 10080180
TI  - Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss
      muscular dystrophy.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures
      of elbows and Achilles tendons, slowly progressive muscle wasting and weakness,
      and a cardiomyopathy with conduction blocks which is life-threatening. Two modes
      of inheritance exist, X-linked (OMIM 310300) and autosomal dominant (EDMD-AD;
      OMIM 181350). EDMD-AD is clinically identical to the X-linked forms of the
      disease. Mutations in EMD, the gene encoding emerin, are responsible for the X
      linked form. We have mapped the locus for EDMD-AD to an 8-cM interval on
      chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype
      in four other small families was potentially linked to this locus. This region
      contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the
      nuclear lamina, lamins A and C, produced by alternative splicing. We identified
      four mutations in LMNA that co-segregate with the disease phenotype in the five
      families: one nonsense mutation and three missense mutations. These results are
      the first identification of mutations in a component of the nuclear lamina as a
      cause of inherited muscle disorder. Together with mutations in EMD (refs 5,6),
      they underscore the potential importance of the nuclear envelope components in
      the pathogenesis of neuromuscular disorders.

PMID- 10080181
TI  - Notch signalling pathway mediates hair cell development in mammalian cochlea.
AB  - The mammalian cochlea contains an invariant mosaic of sensory hair cells and non
      sensory supporting cells reminiscent of invertebrate structures such as the
      compound eye in Drosophila melanogaster. The sensory epithelium in the mammalian
      cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a
      single row of inner hair cells and three rows of outer hair cells. Each hair cell
      is separated from the next by an interceding supporting cell, forming an
      invariant and alternating mosaic that extends the length of the cochlear duct.
      Previous results suggest that determination of cell fates in the cochlear mosaic
      occurs via inhibitory interactions between adjacent progenitor cells (lateral
      inhibition). Cells populating the cochlear epithelium appear to constitute a
      developmental equivalence group in which developing hair cells suppress
      differentiation in their immediate neighbours through lateral inhibition. These
      interactions may be mediated through the Notch signalling pathway, a molecular
      mechanism that is involved in the determination of a variety of cell fates. Here
      we show that genes encoding the receptor protein Notch1 and its ligand, Jagged 2,
      are expressed in alternating cell types in the developing sensory epithelium. In
      addition, genetic deletion of Jag2 results in a significant increase in sensory
      hair cells, presumably as a result of a decrease in Notch activation. These
      results provide direct evidence for Notch-mediated lateral inhibition in a
      mammalian system and support a role for Notch in the development of the cochlear
      mosaic.

PMID- 10080182
TI  - Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance
      gene.
AB  - Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder
      with a worldwide distribution, but with a high prevalence in the Finnish
      population; symptoms include failure to thrive, growth retardation, muscle
      hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of
      dibasic amino acids has been demonstrated at the baso-lateral membrane of
      epithelial cells in small intestine and in renal tubules and in plasma membrane
      of cultured skin fibroblasts from LPI patients. The gene causing LPI has been
      assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA
      (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic amino
      acid transport activity and is located in the LPI region, in 31 Finnish LPI
      patients and 1 Spanish patient. The Finnish patients are homozygous for a founder
      missense mutation leading to a premature stop codon. The Spanish patient is a
      compound heterozygote with a missense mutation in one allele and a frameshift
      mutation in the other. The frameshift mutation generates a premature stop codon,
      eliminating the last one-third of the protein. The missense mutation abolishes
      y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of
      the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis
      oocytes. Our data establish that mutations in SLC7A7 cause LPI.

PMID- 10080183
TI  - SLC7A7, encoding a putative permease-related protein, is mutated in patients with
      lysinuric protein intolerance.
AB  - Lysinuric protein intolerance (LPI, MIM 222700) is an autosomal recessive
      multisystem disorder found mainly in Finland and Italy. On a normal diet, LPI
      patients present poor feeding, vomiting, diarrhoea, episodes of hyperammoniaemic
      coma and failure to thrive. Hepatosplenomegaly, osteoporosis and a life
      threatening pulmonary involvement (alveolar proteinosis) are also seen. LPI is
      caused by defective cationic amino acid (CAA) transport at the basolateral
      membrane of epithelial cells in kidney and intestine. Metabolic derangement is
      characterized by increased renal excretion of CAA, reduced CAA absorption from
      intestine and orotic aciduria. The gene causing LPI was assigned using linkage
      analysis to chromosome 14q11.2 near the T-cell receptor alpha/delta chains locus,
      and a critical region has been defined. We have identified two new transcripts
      (SLC7A8 and SLC7A7) homologous to amino acid transporters, highly expressed in
      kidney and mapping in the LPI critical region. Mutational analysis of both
      transcripts revealed that SLC7A7 (for solute carrier family 7, member 7) is
      mutated in LPI. In five Italian patients, we found either an insertion or
      deletion in the coding sequence, which provides evidence of a causative role of
      SLC7A7 in LPI. Furthermore, we detected a splice acceptor change resulting in a
      frameshift and premature translation termination in four unrelated Finnish
      patients. This mutation may represent the founder LPI allele in Finland.

PMID- 10080184
TI  - Heterozygous mutations in the gene encoding noggin affect human joint
      morphogenesis.
AB  - The secreted polypeptide noggin (encoded by the Nog gene) binds and inactivates
      members of the transforming growth factor beta superfamily of signalling proteins
      (TGFbeta-FMs), such as BMP4 (ref. 1). By diffusing through extracellular matrices
      more efficiently than TGFbeta-FMs, noggin may have a principal role in creating
      morphogenic gradients. During mouse embryogenesis, Nog is expressed at multiple
      sites, including developing bones. Nog-/- mice die at birth from multiple defects
      that include bony fusion of the appendicular skeleton. We have identified five
      dominant human NOG mutations in unrelated families segregating proximal
      symphalangism (SYM1; OMIM 185800) and a de novo mutation in a patient with
      unaffected parents. We also found a dominant NOG mutation in a family segregating
      multiple synostoses syndrome (SYNS1; OMIM 186500); both SYM1 and SYNS1 have
      multiple joint fusion as their principal feature. All seven NOG mutations alter
      evolutionarily conserved amino acid residues. The findings reported here confirm
      that NOG is essential for joint formation and suggest that NOG requirements
      during skeletogenesis differ between species and between specific skeletal
      elements within species.

PMID- 10080185
TI  - High-resolution mapping of quantitative trait loci in outbred mice.
AB  - Screening the whole genome of a cross between two inbred animal strains has
      proved to be a powerful method for detecting genetic loci underlying quantitative
      behavioural traits, but the level of resolution offered by quantitative trait
      loci (QTL) mapping is still too coarse to permit molecular cloning of the genetic
      determinants. To achieve high-resolution mapping, we used an outbred stock of
      mice for which the entire genealogy is known. The heterogeneous stock (HS) was
      established 30 years ago from an eight-way cross of C57BL/6, BALB/c, RIII, AKR,
      DBA/2, I, A/J and C3H inbred mouse strains. At the time of the experiment
      reported here, the HS mice were at generation 58, theoretically offering at least
      a 30-fold increase in resolution for QTL mapping compared with a backcross or an
      F2 intercross. Using the HS mice we have mapped a QTL influencing a psychological
      trait in mice to a 0.8-cM interval on chromosome 1. This method allows
      simultaneous fine mapping of multiple QTLs, as shown by our report of a second
      QTL on chromosome 12. The high resolution possible with this approach makes QTLs
      accessible to positional cloning.

PMID- 10080186
TI  - Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin,
      cause hereditary megaloblastic anaemia 1.
AB  - Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive
      disorder characterized by juvenile megaloblastic anaemia, as well as neurological
      symptoms that may be the only manifestations. At the cellular level, MGA1 is
      characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption.
      MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern
      countries and Norway, and highest in Finland (0.8/100,000). We previously mapped
      the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM
      region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the
      intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human
      homologue, CUBN, was mapped to the same region. We have now refined the MGA1
      region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified
      two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our
      genetic and molecular data indicate that mutations in CUBN cause MGA1.

PMID- 10080187
TI  - Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch
      repair.
AB  - Nucleotide-excision repair (NER) and mismatch repair (MMR) are prominent examples
      of highly conserved DNA repair systems which recognize and replace damaged and/or
      mispaired nucleotides in DNA. In humans, inheritable defects in components of the
      NER system are associated with severe diseases such as xeroderma pigmentosum (XP)
      and Cockayne syndrome (CS), whereas inactivation of MMR is accompanied by
      predisposition to certain types of cancer. In Schizosaccharomyces pombe, the msh2
      and pms1-dependent long-patch MMR system efficiently corrects small
      insertion/deletion loops and all base-base mismatches, except C/C. Up to 70% of
      C/C mismatches generated in recombination intermediates, and to a lesser extent
      also other base-base mismatches, are thought to undergo correction by a minor,
      short-patch excision repair system. We identify here the NER genes rhpl4, swi10
      and rad16 as components of this repair pathway and show that they act
      independently of msh2 and pms1.

PMID- 10080188
TI  - Prox1 function is crucial for mouse lens-fibre elongation.
AB  - Although insights have emerged regarding genes controlling the early stages of
      eye formation, little is known about lens-fibre differentiation and elongation.
      The expression pattern of the Prox1 homeobox gene suggests it has a role in a
      variety of embryonic tissues, including lens. To analyse the requirement for
      Prox1 during mammalian development, we inactivated the locus in mice. Homozygous
      Prox1-null mice die at mid-gestation from multiple developmental defects; here we
      describe the specific effect on lens development. Prox1 inactivation causes
      abnormal cellular proliferation, downregulated expression of the cell-cycle
      inhibitors Cdkn1b (also known as p27KIP1) and Cdkn1c (also known as p57KIP2),
      misexpression of E-cadherin and inappropriate apoptosis. Consequently, mutant
      lens cells fail to polarize and elongate properly, resulting in a hollow lens.
      Our data provide evidence that the progression of terminal fibre differentiation
      and elongation is dependent on Prox1 activity during lens development.

PMID- 10080189
TI  - Reliable identification of large numbers of candidate SNPs from public EST data.
AB  - High-resolution genetic analysis of the human genome promises to provide insight
      into common disease susceptibility. To perform such analysis will require a
      collection of high-throughput, high-density analysis reagents. We have developed
      a polymorphism detection system that uses public-domain sequence data. This
      detection system is called the single nucleotide polymorphism pipeline
      (SNPpipeline). The analytic core of the SNPpipeline is composed of three
      components: PHRED, PHRAP and DEMIGLACE. PHRED and PHRAP are components of a
      sequence analysis suite developed to perform the semi-automated analysis required
      for large-scale genomes (provided courtesy of P. Green). Using these informatics
      tools, which examine redundant raw expressed sequence tag (EST) data, we have
      identified more than 3,000 candidate single-nucleotide polymorphisms (SNPs).
      Empiric validation studies of a set of 192 candidates indicate that 82% identify
      variation in a sample of ten Centre d'Etudes Polymorphism Humain (CEPH)
      individuals. Our results suggest that existing sequence resources may serve as a
      valuable source for identifying genetic variation.

PMID- 10080190
TI  - Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and
      cellular proliferation.
AB  - c-Jun is a major component of the heterodimeric transcription factor AP-1 and is
      essential for embryonic development, as fetuses lacking Jun die at mid-gestation
      with impaired hepatogenesis and primary Jun-/- fibroblasts have a severe
      proliferation defect and undergo premature senescence in vitro. c-Jun and AP-1
      activities are regulated by c-Jun N-terminal phosphorylation (JNP) at serines 63
      and 73 through Jun N-terminal kinases(JNKs). JNP is thought to be required for
      the anti-apoptotic function of c-Jun during hepatogenesis, as mice lacking the
      JNK kinase SEK1 exhibit liver defects similar to those seen in Jun-/- fetuses. To
      investigate the physiological relevance of JNP, we replaced endogenous Jun by a
      mutant Jun allele with serines 63 and 73 mutated to alanines (Jun(tm1wag);
      hereafter referred to as JunAA). Here we show that primary JunAA fibroblasts have
      proliferation- and stress-induced apoptotic defects, accompanied by reduced AP-1
      activity. JunAA mice are viable and fertile, smaller than controls and resistant
      to epileptic seizures and neuronal apoptosis induced by the excitatory amino acid
      kainate. Primary mutant neurons are also protected from apoptosis and exhibit
      unaltered JNK activity. Our results provide evidence that JNP is dispensable for
      mouse development, and identify c-Jun as the essential substrate of JNK
      signalling during kainate-induced neuronal apoptosis.

PMID- 10080191
TI  - Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma.
AB  - Protein tyrosine phosphatase sigma (PTP-sigma, encoded by the Ptprs gene) is a
      member of the LAR subfamily of receptor-like protein tyrosine phosphatases that
      is highly expressed during mammalian embryonic development in the germinal cell
      layer lining the lateral ventricles of the developing brain, dorsal root ganglia,
      Rathke's pouch, olfactory epithelium, retina and developing lung and heart. On
      the basis of its expression and homology with the Drosophila
      melanogasterorthologues DPTP99 and DPTP100A (refs 5,6), which have roles in the
      targeting of axonal growth cones, we hypothesized that PTP-sigma may also have a
      modulating function in cell-cell interactions, as well as in axon guidance during
      mammalian embryogenesis. To investigate its function in vivo, we generated Ptprs
      deficient mice. The resulting Ptprs-/-animals display retarded growth, increased
      neonatal mortality, hyposmia and hypofecundity. Anatomical and histological
      analyses showed a decrease in overall brain size with a severe depletion of
      luteinizing hormone-releasing hormone (LHRH)-immunoreactive cells in Ptprs-/-
      hypothalamus. Ptprs-/- mice have an enlarged intermediate pituitary lobe, but
      smaller anterior and posterior lobes. These results suggest that tyrosine
      phosphorylation-dependent signalling pathways regulated by PTP-sigma influence
      the proliferation and/or adhesiveness of various cell types in the developing
      hypothalamo-pituitary axis.

PMID- 10080192
TI  - Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor
      tyrosine phosphatase PTPsigma.
AB  - The LAR-family protein tyrosine phosphatase sigma (PTPsigma, encoded by the gene
      Ptprs) consists of a cell adhesion-like extracellular domain composed of
      immunoglobulin and fibronectin type-III repeats, a single transmembrane domain
      and two intracellular catalytic domains. It was previously shown to be expressed
      in neuronal and lung epithelial tissues in a developmentally regulated manner. To
      study the role of PTPsigma in mouse development, we inactivated Ptprs by gene
      targeting. All Ptprs+/- mice developed normally, whereas 60% of Ptprs-/- mice
      died within 48 hours after birth. The surviving Ptprs-/- mice demonstrated
      stunted growth, developmental delays and severe neurological defects including
      spastic movements, tremor, ataxic gait, abnormal limb flexion and defective
      proprioception. Histopathology of brain sections revealed reduction and
      hypocellularity of the posterior pituitary of Ptprs-/- mice, as well as a
      reduction of approximately 50-75% in the number of choline acetyl transferase
      positive cells in the forebrain. Moreover, peripheral nerve electrophysiological
      analysis revealed slower conduction velocity in Ptprs-/- mice relative to wild
      type or heterozygous animals, associated with an increased proportion of slowly
      conducting, small-diameter myelinated fibres and relative hypomyelination. By
      approximately three weeks of age, most remaining Ptprs-/- mice died from a
      wasting syndrome with atrophic intestinal villi. These results suggest that
      PTPsigma has a role in neuronal and epithelial development in mice.

PMID- 10080193
TI  - Retinal vein occlusions.

PMID- 10080194
TI  - Glaucoma and quality-of-life.

PMID- 10080195
TI  - Ocular dominance.

PMID- 10080196
TI  - Success rate of endoscopic laser-assisted dacryocystorhinostomy.

PMID- 10080197
TI  - Menkes disease.

PMID- 10080198
TI  - Neural retinal cell transplantation: ideal versus reality.

PMID- 10080199
TI  - Randomized bilateral comparison of excimer laser in situ keratomileusis and
      photorefractive keratectomy for 2.50 to 8.00 diopters of myopia.
AB  - OBJECTIVE: To compare effectiveness, safety, and stability of excimer laser in
      situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for low-to
      moderate myopia. DESIGN: Prospective, randomized, bilateral study. PARTICIPANTS:
      Thirty-three patients with a manifest refraction of -2.50 to -8.00 diopters (D)
      participated. INTERVENTION: For each patient, one eye received LASIK and the
      other received PRK. The first eye treated, and surgical method in the first eye,
      were randomized. Both eyes were treated by the same surgeon during the same
      operative session with a Summit Omnimed I laser (6-mm-diameter ablation) and a
      Chiron Automated Corneal Shaper. Follow-up was 90% at 1 and 2 years. RESULTS: At
      baseline, mean (+/-standard deviation) spherical equivalent manifest refraction
      was -4.80 +/- 1.60 D in LASIK-treated eyes and -4.70 +/- 1.50 D in PRK-treated
      eyes. At 1 day after surgery, 81% of patients (21 eyes) reported no pain in the
      LASIK-treated eye, whereas no patient (0%) reported being pain-free in the PRK
      treated eye. At 3 to 4 days after surgery, 18 (80%) LASIK-treated eyes either
      improved or remained within 1 line of baseline spectacle-corrected visual acuity;
      only 10 (45%) PRK-treated eyes achieved this result. At 2 years after surgery, 18
      (61%) LASIK- and 10 (36%) PRK-treated eyes achieved an uncorrected visual acuity
      of 20/20 or better, with no statistically significant difference in refractive
      outcome between the two techniques. Quantitative videokeratography showed more
      regularity after LASIK. Complications were similar in the two groups. Patients
      preferred LASIK by a margin of 2 to 1 at 1 year but showed no preference at 2
      years. CONCLUSIONS: Using a 6-mm-diameter single-pass, large area ablation and an
      automated microkeratome to treat myopia of -2.50 to -8.00 D with 1.00 D or less
      astigmatism in 1994, the authors used LASIK to produce a higher percentage of
      eyes with an uncorrected visual acuity of 20/20 or better, more regular
      postoperative corneal topography, less postoperative pain, and more rapid
      recovery of baseline spectacle-corrected visual acuity than PRK. Both LASIK and
      PRK achieved successful correction of low-to-moderate myopia at 1 and 2 years
      after surgery.

PMID- 10080200
TI  - Phakic anterior chamber lenses for the correction of myopia: a 7-year cumulative
      analysis of complications in 263 cases.
AB  - OBJECTIVE: To perform a prospective, clinical trial to determine the potential
      cumulative complications of patients implanted with angle-supported phakic
      intraocular lenses (PIOLs) for the correction of myopia. DESIGN: Nonrandomized,
      prospective, comparative trial. PARTICIPANTS: Two hundred sixty-three eyes of 160
      consecutive patients were included. INTERVENTION: Angle-supported anterior
      chamber intraocular lenses were implanted into phakic eyes. MAIN OUTCOME
      MEASURES: Night halos and glare were recorded. Central endothelial cell count,
      postoperative inflammation, applanation tonometry, cataract development, retinal
      detachment, and pupil ovalization were recorded by the same physician. RESULTS:
      Night halos and glare were reported as significant by 20.2% at 1 year and 10% at
      year 7 of follow-up. This complication was significantly lower in the larger
      optical zone PIOL (ZSAL-4) than in the ZB5M/ZB5MF group (P < 0.05). Acute
      postoperative iritis was observed in 4.56% of cases. High intraocular pressure
      that required antiglaucoma medications appeared in 7.2% of cases. Central corneal
      endothelial cell density was significantly decreased at postoperative month 3 (P
      < 0.0001). The percentages of cell loss were 3.76% at month 3 and 1.83% at year
      1, and then the percentages decreased by 1.37% more at year 2, 0.72% at year 3,
      0.3% at year 4, 0.6% at year 5, 0.4% at year 6, and 0.56% at year 7. The total
      cumulative loss of central endothelial cells after 7 years was 8.37%. Pupil
      ovalization was present in 5.9% of cases, although smaller degrees of this
      complication were observed in another 10.3%. Retinal detachment appeared in 3% of
      cases. The PIOL explantation was decided in 11 cases (4.18%) because of cataract
      development (9 cases) and extreme pupil ovalization associated with severe glare
      (2 cases). The Kaplan-Meier cumulative survival analysis study showed an expected
      period free from complication of 86.5% for IOP elevation, 98.75% for endothelial
      cell count inferior to 1500 cells/mm2, 86.97% for pupil ovalization, 95.43% for
      retinal detachment, and 89.02% for explantation. CONCLUSIONS: Angle-supported
      PIOL appeared to be well tolerated by the corneal endothelium with a low rate of
      other complications. Pupil ovalization seemed to be a specific problem for this
      type of PIOL.

PMID- 10080201
TI  - Patterns of late corneal scarring after photorefractive keratectomy in high and
      severe myopia.
AB  - OBJECTIVE: To study the correlation between scarring 1 year after photorefractive
      keratectomy (PRK), final refraction, and degree of myopia. DESIGN: A
      retrospective, noncomparative case series. PARTICIPANTS: One hundred twenty eyes
      of 78 patients underwent PRK for high and severe myopia. Thirty-nine eyes had a
      pre-PRK spherical equivalent (SE) between -9.5 and -18.25 diopters (D) (severe
      myopia). Eighty-one eyes had a pre-PRK SE between -6.25 and -9.25 D (high
      myopia). Follow-up time ranged between 12 and 37 months with a mean of 18.2
      months. INTERVENTION: Multizone PRK with the VISX 20/20 excimer laser. MAIN
      OUTCOME MEASURES: Corneal scarring, final best-corrected visual acuity (BCVA),
      and refraction. RESULTS: There were 71.7% of eyes with severe myopia and 60.5% of
      eyes with high myopia found to have any pattern of stromal scarring, which was
      classified as focal, semiannular, annular, and discoid. Discoid scars were rare
      (6.6%) and found in 12.8% of severe myopic eyes compared to 3.7% of high myopic
      eyes. Only 50% of the eyes with a discoid scar achieved final BCVA between 6/6
      and 6/9 compared to 81.6% of the eyes with a clear cornea. The severe myopic eyes
      with a discoid scar had the highest level of final undercorrection (-5.0 D)
      compared to a maximum of -1.5 D in the high myopia group. The severe myopic eyes
      with a discoid scar had a higher number of retreatments (4 of 5) compared to the
      high myopia group (1 of 3). Other types of scars were less clinically
      significant. CONCLUSIONS: Photorefractive keratectomy was efficient in the
      correction of high myopia but less so in severe myopia, in which discoid scarring
      was more frequent and more clinically significant, being associated with
      significant regression. Other types of scarring were less clinically significant.

PMID- 10080202
TI  - Very high-frequency ultrasound corneal analysis identifies anatomic correlates of
      optical complications of lamellar refractive surgery: anatomic diagnosis in
      lamellar surgery.
AB  - OBJECTIVE: To examine the utility of very high-frequency (VHF) ultrasound
      scanning in determining the anatomic changes and correlates of optical
      complications in lamellar refractive surgery. STUDY DESIGN: Case series.
      PARTICIPANTS: Cases analyzed included marked asymmetric astigmatism postautomated
      lamellar keratoplasty (ALK), image ghosting despite normal videokeratography post
      ALK, uncomplicated myopic laser in situ keratomileusis (LASIK), and hyperopic
      LASIK with regression. METHODS: A prototype VHF ultrasound scanner (50 MHz) was
      used to obtain sequences of parallel B-scans of the cornea. Digital signal
      processing techniques were used to measure epithelial, stromal, and flap
      thickness values in a grid encompassing the central 4 to 5 mm of the cornea,
      enabling pachymetric mapping of each layer with 2-micron precision. MAIN OUTCOME
      MEASURE: The appearance of the corneas in VHF ultrasound images and thickness
      values of individual corneal layers determined from VHF ultrasound data. RESULTS:
      VHF ultrasound resolved the epithelial, stromal cap, or flap and residual stromal
      layers 1 year after lamellar surgery. Asymmetric stromal tissue removal was
      differentiated from stromal cap irregularity. Epithelium acted to compensate for
      asymmetry of the stromal surface about the visual axis and for localized surface
      irregularities. Irregularities in the epithelial-stromal interface accounted for
      image ghosting present despite apparently normal videokeratography. Epithelial
      thickening was shown after uncomplicated myopic LASIK. Hyperopic LASIK
      demonstrated relative epithelial thickening localized to the region of ablation
      accounting for refractive regression. CONCLUSIONS: VHF ultrasound shows promise
      as a sensitive method of determining the anatomic correlates of optical
      complications in lamellar refractive surgery.

PMID- 10080203
TI  - Comparison of mechanical and transepithelial debridement during photorefractive
      keratectomy.
AB  - OBJECTIVE: Comparison of clinical results from mechanical and transepithelial
      debridement during photorefractive keratectomy. DESIGN: Randomized, prospective
      study. PARTICIPANTS: Two hundred seventy-eight eyes in 173 patients between
      November 1995 and June 1997. INTERVENTION: Photorefractive keratectomy treatments
      with a Summit Omnimed excimer laser (6-mm). Clinical results were measured at 1,
      3, and 6 months. MAIN OUTCOMES MEASURES: Uncorrected visual acuity (UCVA), best
      spectacle-corrected visual acuity (BCVA), mean spherical equivalent (MSE),
      astigmatism, corneal haze, and subjective vision (day, night, glare, and halo).
      RESULTS: At all postoperative intervals, no significant difference was present
      between mean values of MSE, haze, or any subjective parameters. For mean UCVA,
      BCVA, and astigmatism values, a significant difference (P < 0.05) was present
      only at 6 months. At all postoperative intervals, mechanical values tended to be
      superior to transepithelial valves. CONCLUSION: Clinical results were not
      statistically different between the two techniques; however, the mechanical
      technique tended to have superior values for almost all tested parameters.

PMID- 10080204
TI  - Acute corneal necrosis after excimer laser keratectomy for hyperopia.
AB  - OBJECTIVE: To describe a new, rare clinical complication after routine excimer
      laser photorefractive keratectomy to correct hyperopia. DESIGN: Case report with
      clinicopathologic correlation. MAIN OUTCOME MEASURES: Four weeks after treatment
      with excimer laser, a perforating keratoplasty was performed for persistent
      corneal opacities. The corneal button was examined using light and electron
      microscopy. Special immunohistochemical stains were used to detect apoptosis.
      RESULTS: The patient developed corneal opacities, endothelial precipitates, and a
      fibrinous exudate in the anterior chamber after the laser treatment. The changes
      did not respond to therapy directed against bacteria, fungi, and Acanthamoeba.
      All examinations and special stains were negative for micro-organisms. By light
      microscopy, an anterior zone of corneal necrosis was present with a moderate
      amount of acute inflammatory cells. At the interface between necrotic and viable
      corneal stroma, keratocytes with typical features of apoptosis were detected by
      immunohistochemistry and electron microscopy. CONCLUSION: This is the first full
      histopathologic report of a case of acute corneal necrosis with signs of
      apoptosis after excimer laser therapy of the cornea. Surgeons should be aware of
      this rare but potentially severe complication.

PMID- 10080205
TI  - Burden of moderate visual impairment in an urban population in southern India.
AB  - OBJECTIVE: To assess the prevalence and causes of moderate visual impairment in
      an urban population in southern India. DESIGN: Population-based, cross-sectional
      study. PARTICIPANTS: A total of 2522 (85.4% of the eligible) persons of all ages,
      including 1399 persons 30 years of age or older, from 24 clusters representative
      of the population of Hyderabad city. TESTING: The eligible subjects underwent a
      detailed ocular evaluation, including logarithm of the minimum angle of
      resolution (logMAR) visual acuity, refraction, slit-lamp biomicroscopy,
      applanation tonometry, gonioscopy, cataract grading, and stereoscopic dilated
      fundus evaluation. Automated threshold visual fields and slit-lamp and fundus
      photography were done when indicated by standardized criteria. MAIN OUTCOME
      MEASURE: Moderate visual impairment was defined as presenting distance visual
      acuity less than 20/40 to 20/200 or visual field loss by predefined standardized
      conservative criteria in the better eye. RESULTS: In addition to the 1%
      prevalence of blindness in this sample reported earlier, moderate visual
      impairment was present in 303 subjects, an age-gender-adjusted prevalence of 7.2%
      (95% confidence interval [CI], 4.5%-9.9%; design effect, 2.7). The major cause of
      moderate visual impairment was refractive error (59.4%, 95% CI, 52.3%-66.5%)
      followed by cataract (25.3%, 95% CI, 19%-31.6%). Multivariate analysis showed
      that the prevalence of moderate visual impairment was significantly higher in
      those 40 years of age or older (odds ratio, 10.9; 95% CI, 8-15) and females (odds
      ratio, 1.89; 95% CI, 1.41-2.53) and lower in those belonging to the highest
      socioeconomic status (odds ratio, 0.27; 95% CI, 0.14-0.51). However, because of
      the pyramidal age distribution of the population, 38.1% of the total moderate
      visual impairment was present in those younger than 40 years of age. The
      proportion of moderate visual impairment caused by refractive error was higher in
      the younger than in the older age groups (P < 0.0001). CONCLUSIONS: Projecting
      the results to the 26.5% urban population of India, there would be 18.4 million
      (95% CI, 11.5-25.2 million) persons with moderate visual impairment in urban
      India alone. Refractive error was the major cause of moderate visual impairment
      in the population studied. The absolute proportion of moderate visual impairment
      in those younger than 40 years of age was considerable. The eyecare policy of
      India, apart from dealing with blindness, should address the issue of the
      relatively easily treatable uncorrected refractive error as the cause of moderate
      visual impairment in an estimated 10.9 million persons in urban India.

PMID- 10080206
TI  - Complications associated with pegging hydroxyapatite orbital implants.
AB  - OBJECTIVE: Prior studies of hydroxyapatite orbital implant complications have
      primarily focused on complications of the implant itself with only occasional
      mention of the complications associated with the peg system. This in part may be
      because of a low rate of pegging and, thus, a small sample size to evaluate.
      Therefore, a full range of complications that can occur with pegging has not been
      presented. The objective of this study was to determine the complications
      associated with pegging and to discuss ways to manage them. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS/INTERVENTION: The authors
      analyzed all of the complications associated with pegging 165 of a possible 275
      hydroxyapatite implants implanted by 2 surgeons over 7 years. MAIN OUTCOME
      MEASURES: The following data were recorded: type of surgery performed, size of
      implant used, type of hydroxyapatite used, peg system used, time of pegging,
      follow-up duration, problems encountered, and treatment. RESULTS: Sixty-two
      (37.5%) of the 165 patients who had pegged implants were found to have problems
      with their pegs. Twenty-one (33.8%) of the 62 patients with peg problems had more
      than 1 peg-related problem. Complications associated with pegging included
      discharge (37%; 23 of 62), pyogenic granulomas (30.6%; 19 of 62), peg falling out
      (29%; 18 of 62), poor transfer of movement (11.2%; 7 of 62), clicking (11.2%; 7
      of 62), conjunctiva overgrowing peg (4.8%; 3 of 62), poor-fitting sleeve (4.8%; 3
      of 62), part of sleeve shaft visible (4.8%; 3 of 62), peg drilled on an angle
      (4.8%; 3 of 62), hydroxyapatite visible around peg hole (3.2%; 2 of 62), peg
      drilled off-center (3.2%; 2 of 62), popping peg (3.2%; 2 of 62), and excess
      movement of peg (3.2%; 2 of 62). The most serious complication occurring in two
      individuals (3.2%) was implant infection requiring implant removal. CONCLUSION:
      There are several potential complications that can occur after pegging the
      hydroxyapatite implant. These problems are generally of a minor nature but often
      require additional patient visits that would not ordinarily have been required if
      the peg was not in place. The most serious peg problem is implant infection,
      which may necessitate implant removal. These potential peg problems should be
      reviewed with the patient before the procedure is performed.

PMID- 10080207
TI  - Comparative motility of hydroxyapatite and alloplastic enucleation implants.
AB  - OBJECTIVE: To compare the motility of scleral-covered hydroxyapatite and
      alloplastic enucleation implants. DESIGN: Retrospective, nonrandomized
      comparative trial. PARTICIPANTS: Measurements were obtained after surgery in 76
      anophthalmic patients who had received either hydroxyapatite or alloplastic
      enucleation implants. METHODS/MAIN OUTCOME MEASURES: Horizontal and vertical
      excursions of the enucleation implants. RESULTS: There is no clinically important
      difference between the movement of hydroxyapatite and alloplastic enucleation
      implants. Implant movement appears to decline with advancing age. CONCLUSION:
      Scleral-covered alloplastic and hydroxyapatite enucleation implants show similar
      movement. Although directly coupling hydroxyapatite implants to the prosthesis
      via the motility peg provides enhanced prosthetic movement, there appears to be
      no motility benefit of nonpegged hydroxyapatite over spherical alloplastic
      implants.

PMID- 10080208
TI  - Stabilization of eyelid height after aponeurotic ptosis repair.
AB  - OBJECTIVE: To develop guidelines for revision of ptosis surgery in the early
      postoperative period by establishing what percentage of eyelids after anterior
      levator advancement have reached their final height by the first postoperative
      week. DESIGN: Prospective noncomparative case series. PARTICIPANTS: An analysis
      was performed on 164 eyelids in 97 patients with involutional aponeurotic ptosis.
      INTERVENTION: Anterior levator advancement was performed on each of these 164
      eyelids. Exclusion criterion consisted of a history or evidence of neurologic or
      muscular disease, preceding trauma, an anophthalmic socket, or prior eyelid
      surgery. MAIN OUTCOME MEASURES: The marginal reflex distance, eyelid excursion,
      and degree of swelling were recorded perioperatively; additionally, photographs
      were obtained before surgery and at 1 and 6 weeks after surgery. RESULTS: At 1
      week after surgery, only 40% of eyelids had reached their final height; 52%
      continued to rise a mean of 1.1 mm. The percentage of eyelids continuing to rise
      after the first postoperative week varied with the amount of swelling present at
      1 week, although a direct correlation did not exist (Pearson correlation, 0.22; P
      < 0.26). Although this increase ranged from 0.5 to 3.0 mm for 71% of eyelids, the
      subsequent increase was 1 mm or less. Maximal eyelid height was achieved almost
      universally by 6 weeks, after which 18% of eyelids subsequently dropped a mean of
      0.8 mm. CONCLUSIONS: Based on this study, the authors suggest revision at 1 week
      after anterior levator advancements in which minimal-to-moderate eyelid swelling
      exists for contour abnormalities, if the eyelid height is 0.5 mm or more above or
      more than 1.0 mm below the target height, or if asymmetry between the eyelids is
      1.0 mm or more. The authors do not advise early revision for patients with
      excessive swelling still present 1 week after surgery.

PMID- 10080209
TI  - Penetrating orbital injury with organic foreign bodies.
AB  - OBJECTIVE: The authors reviewed the clinical features, diagnostic workup, and
      management of patients of penetrating orbital injuries with retained organic
      foreign bodies. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS:
      Nineteen patients (15 males, 4 females) with penetrating orbital injuries due to
      organic foreign bodies. RESULTS: The series included 15 (78.9%) males and 4
      (21.1%) females who ranged in age from 6 months to 40 years (mean = 14.6 years);
      12 (63.2%) patients were younger than 12 years of age. Twelve (63.2%) right and 7
      (36.8%) left orbits were involved. Time between injury and presentation varied
      from a few hours to 9 months. Most common injury site was the superior orbit in
      11 (57.9%) patients leading to abnormal extraocular motility (84.2%), proptosis
      (68.4%), and upper lid ptosis (47.4%). Associated pathologies also included acute
      cellulitis in 11, orbitocutaneous fistula in 5, and osteomyelitis in 2 patients.
      Preoperative computed tomography (CT) and magnetic resonance imaging (MRI)
      identified the foreign bodies in 42% and 57% of the patients, respectively.
      CONCLUSION: Preoperative identification of the foreign material in the orbit was
      found to be very helpful for patient management but was only possible in
      approximately 50% of our cases with the use of CT and MRI. The vision in our
      patients usually improved shortly after treatment; the long-term complications
      more often included extraocular muscle and eyelid motility problems and
      periorbital scarring.

PMID- 10080210
TI  - Ocular injuries from paintball pellets.
AB  - OBJECTIVE: To evaluate the ocular effects of blunt trauma due to injury from a
      paintball pellet. DESIGN: Noncomparative case series. PARTICIPANTS: Thirteen
      patients who suffered ocular injury from paintballs are described. The patients
      presented to six different civilian and military emergency departments in
      tertiary care medical centers. INTERVENTION: Patients were treated for the ocular
      injury. MAIN OUTCOME MEASURES: Patients were evaluated for initial and final
      visual acuity. The reason for persistent loss of vision was delineated. RESULTS:
      There were 12 males and 1 female with an average age of 21 years (range, 12-33
      years). Eleven of the 13 had no ocular protection at the time of the ocular
      injury. On initial examination, nine patients had a hyphema, nine had a vitreous
      hemorrhage, six had a retinal tear or detachment, three had corneal or corneal
      scleral ruptures, and one had traumatic optic neuropathy. The final visual acuity
      was 20/40 or better in two patients, 20/50 to 20/150 in three patients, and
      20/200 or worse in eight patients. CONCLUSION: Injuries due to paintball pellets
      can result in severe ocular damage and significant loss of vision. Eyecare
      professionals should be aware of the risks of this sport and must strongly advise
      participants to wear adequate protection when involved in this activity.

PMID- 10080211
TI  - Microendoscopic trabecular surgery in glaucoma management.
AB  - OBJECTIVE: To evaluate the safety and efficacy of trabecular surgery under
      microendoscopic control in the management of advanced chronic open-angle glaucoma
      when the presence of corneal opacification obscures adequate visualization of the
      anterior segment. STUDY DESIGN: Comparative interventional case series.
      PARTICIPANTS AND INTERVENTION: Fifteen eyes of 15 patients with medically
      uncontrolled open-angle glaucoma and moderate-to-severe corneal opacification
      underwent trabecular surgery under microendoscopic control. Seven eyes were
      treated by photoablative laser goniopuncture and eight eyes by goniocurettage.
      MAIN OUTCOME MEASURES: The intraocular pressure (IOP) and number of medications
      before and after surgery were measured. Intraoperative and postoperative
      complications were analyzed. RESULTS: The ophthalmic microendoscope was
      successfully used in visualizing and identifying the anterior chamber angle
      structures and in controlling the trabecular surgical procedures in all eyes. The
      IOP dropped from 34.5 +/- 6.9 millimeters of mercury (mmHg) (range, 27-46 mmHg)
      under maximal-tolerated medical therapy before surgery to 18.5 +/- 3.0 mmHg
      (range, 15-23 mmHg) at 21 months after surgery. Medication averaged 2.3 +/- 0.6
      before surgery and dropped to 1.0 +/- 0.7 at last follow-up. No difference was
      observed in the surgical outcome between the laser-treated eyes and those
      receiving goniocurettage. No severe intraoperative or postoperative complications
      relating to either the trabecular surgery or to the use of the microendoscope
      were observed. CONCLUSION: The ophthalmic microendoscope appears to be safe and
      effective in simultaneously providing illumination, video recording, and clear
      endoscopic view of the fine details of the anterior chamber angle structures.
      Microendoscopy enables various trabecular surgical procedures, such as
      goniocurettage or photoablative laser goniopuncture, which can be performed in
      the presence of corneal opacification that might otherwise preclude adequate
      visualization and treatment. It thus appears that microendoscopic trabecular
      surgery may in the future be considered as an alternative choice of surgical
      treatment in some cases of open-angle glaucoma.

PMID- 10080212
TI  - Augmentation of filtering blebs with perfluoropropane gas bubble: an experimental
      and pilot clinical study.
AB  - OBJECTIVE: To evaluate the use of perfluoropropane (C3F8) gas bubble in the
      augmentation of glaucoma-filtering blebs. DESIGN: Experimental animal study and a
      pilot clinical study. PARTICIPANTS: Twenty rabbits in the animal study and 20
      humans in the pilot study participated. INTERVENTION: Twenty patients underwent
      trabeculectomy for medically uncontrolled glaucoma. Surgical techniques were
      similar to those used in standard limbus-based trabeculectomies. The Tenon's
      capsule and conjunctival wound were closed separately using continuous sutures.
      Before the final knots were tied, 0.1 to 0.2 ml of 15%:85%-C3F8:air mixture gas
      bubble was introduced into the subconjunctival space with a silicone tube
      attached to a 27-gauge Rycrof cannula. The sutures were immediately knotted on
      withdrawal of the tube. The patients were reviewed after surgery for the
      appearance, size, and location of the gas bubble. The bleb morphology and
      intraocular pressures were also monitored. MAIN OUTCOME MEASURES: The parameters
      measured were intraocular pressure control, Snellen visual acuity, appearance of
      the bleb in relation to its elevation and degree of inflammation of the
      subconjunctival tissue, and characteristics of the gas bubble (e.g., size,
      number, and position). RESULTS: The gas bubbles stayed in the conjunctival bleb
      for an average duration of 17 days (range, 13-27 days). In all cases, the gas
      bubbles helped to maintain the filtering bleb until their complete resolution. No
      excessive inflammation was noted in the filtering blebs. The mean preoperative
      intraocular pressure was 27.3 +/- 5.5 millimeters of mercury (mmHg), and the mean
      postoperative intraocular pressure was 14.5 +/- 2.3 mmHg, with only two patients
      requiring supplementary topical medication. All cases resulted in good filtering
      blebs with satisfactory intraocular pressures after 16 months of follow-up.
      CONCLUSIONS: Subconjunctival C3F8 gas bubbles, via a "spacer" effect, aid the
      maintenance of filtering blebs in the early postoperative period. This technique
      may be useful in augmenting or salvaging blebs at risk of failure.

PMID- 10080213
TI  - A 12-month, randomized, double-masked study comparing latanoprost with timolol in
      pigmentary glaucoma.
AB  - OBJECTIVE: To compare the efficacy and side effects and the effect on aqueous
      humor dynamics of 0.005% latanoprost applied topically once daily with 0.5%
      timolol given twice daily for 12 months to patients with pigmentary glaucoma.
      DESIGN: Prospective, randomized, double-masked, clinical study. PARTICIPANTS:
      Thirty-six patients affected with bilateral pigmentary glaucoma controlled with
      no more than a single hypotensive medication were enrolled in the study.
      INTERVENTION: The sample population was randomly divided into 2 age- and gender
      matched groups each of 18 patients. Group 1 received 0.005% latanoprost eyedrops
      once daily and the vehicle (placebo) once daily; group 2 was assigned to timolol
      0.5% eyedrops twice daily. MAIN OUTCOME MEASURES: Diurnal curves of intraocular
      pressure (IOP) were performed on the baseline day and after 0.5, 3, 6, and 12
      months of treatment. The IOP measurements were performed at 8:00 AM, 12:00 noon,
      4:00 PM, and 8:00 PM. Outflow facility ("C") was measured on the baseline day and
      on the last day of the study with a Schiotz electronic tonometer. A two-tailed
      Student's t test for paired or unpaired data was used for statistical evaluation
      of differences between treatment and baseline values or between the latanoprost
      and timolol group. Diurnal IOP measurements were compared hour by hour. Mean
      values of the two eyes IOP and "C" were used for analysis. RESULTS: Compared with
      baseline measurements, both latanoprost and timolol caused a significant (P <
      0.001) reduction of IOP at each hour of diurnal curve throughout the duration of
      therapy. Reduction of IOP was 6.0 +/- 4.5 and 5.9 +/- 4.6 with latanoprost and
      4.8 +/- 3.0 and 4.6 +/- 3.1 with timolol after 6 and 12 months, respectively.
      Comparison of mean diurnal measurements with latanoprost and timolol showed a
      statistical significant (P < 0.001) difference at 3, 6, and 12 months. Mean "C"
      was found to be significantly enhanced (+30%) only in the latanoprost-treated
      group compared with the baseline (P = 0.017). Mean conjunctival hyperemia was
      graded at 0.3 in latanoprost-treated eyes and 0.2 in timolol-treated eyes. A
      remarkable change in iris color was observed in both eyes of 1 of the 18 patients
      treated with latanoprost and none of the 18 patients who received timolol.
      Darkening of the peripheral iris stroma was suspected in two patients treated
      with latanoprost. In the timolol group, heart rate was significantly reduced from
      72 +/- 9 at baseline to 67 +/- 10 beats per minute at 12 months. CONCLUSIONS:
      Although further studies may need to confirm these data on a larger sample and to
      evaluate the side effect of increased iris pigmentation on long-term follow-up,
      in patients with pigmentary glaucoma, 0.005% latanoprost taken once daily was
      well tolerated and more effective in reducing IOP than 0.5% timolol taken twice
      daily.

PMID- 10080214
TI  - Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human
      and animal studies.
AB  - OBJECTIVES: To investigate conjunctival and trabecular specimens from patients
      with glaucoma according to the duration and number of drugs received before
      filtration surgery, and to confirm, in a complementary experimental model, the
      role of preservative by comparing the effects of preserved and nonpreserved
      timolol. STUDY DESIGN: Experimental animal and human tissue study. PARTICIPANTS:
      Paired specimens of conjunctiva and trabeculum were taken from 61 patients
      undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs
      for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5
      underwent primary surgery. A second study was performed in 25 rats receiving
      topical solutions in both eyes for 1 month. INTERVENTION: Immunohistochemistry
      was performed in all biopsy specimens using 12 different monoclonal antibodies.
      Ocular structures from rats treated for 1 month with preserved 0.5% timolol,
      nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly
      investigated in an experimental study. MAIN OUTCOME MEASURES: Inflammatory cell
      infiltrates and fibroblasts were evaluated in biopsies, as well as in animal
      specimens, together with histologic changes induced by the drugs applied.
      RESULTS: Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from
      multitreated patients were found to be abnormally infiltrated by cells expressing
      inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9
      of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the
      primary surgery group were abnormal. In rats, preserved timolol and benzalkonium
      similarly showed infiltrates together with toxic histopathologic changes as
      compared to the nonpreserved timolol and control groups. CONCLUSIONS: These two
      combined studies confirmed histopathologic effects of antiglaucomatous drugs on
      the conjunctiva and showed similar effects in the trabecular meshwork. The
      experimental study showed that benzalkonium chloride is at least, to a large
      part, responsible for these toxic or immunoinflammatory effects or both on the
      ocular structures.

PMID- 10080215
TI  - Acute effects of cigarette smoking on tissue circulation in human optic nerve
      head and choroid-retina.
AB  - OBJECTIVE: To study the acute effects of cigarette smoking on tissue circulation
      in the human optic nerve head (ONH) and choroid-retina. DESIGN: Nonrandomized,
      comparative trial (sequential self-controlled). PARTICIPANTS: Nine healthy
      habitual smokers (age, 28 +/- 4 years; number of cigarettes smoked per day, 27 +/
      10; length of smoking history, 10 +/- 4 years; mean +/- standard deviation).
      INTERVENTION: Using the laser speckle method, normalized blur (NB) value, a
      quantitative index of tissue blood velocity, was measured every 0.125 second and
      averaged over three pulses across an area located in the temporal site of the ONH
      free of visible surface vessels (NB(ONH)) and across an area located halfway
      between the macula and the ONH with no discrete vessels visible (NB(ch-ret)).
      NB(ONH), NB(ch-ret), and intraocular pressure (IOP) in one randomly chosen eye,
      and blood pressure (BP) and pulse rate (PR) were measured before and 1, 5, 10,
      15, 20, 25, 30, 45, 60, and 90 minutes after sham smoking using a short drinking
      straw as a cigarette substitute (control). One week later, NB(ONH), NB(ch-ret),
      and IOP in the same eye, and BP and PR were measured after cigarette smoking
      according to the same time schedule as in the control experiment. MAIN OUTCOME
      MEASURES: NB(ONH) and NB(ch-ret). RESULTS: In the control experiment, all
      parameters examined showed no significant change during the experimental period.
      Differences in NB(ONH) and NB(ch-ret) before and after actual smoking were
      significantly greater than those in the control experiment (analysis of variance,
      P = 0.0000, 0.0000). BP and PR were significantly increased between 1 and 30
      minutes after actual smoking as compared with control data, while IOP showed no
      significant change at any time of measurement. CONCLUSIONS: These results
      indicated that cigarette smoking increased tissue blood velocity in the ONH and
      possibly in the choroid in habitual smokers.

PMID- 10080216
TI  - Evaluation of focal defects of the nerve fiber layer using optical coherence
      tomography.
AB  - OBJECTIVE: To analyze glaucomatous eyes with known focal defects of the nerve
      fiber layer (NFL), relating optical coherence tomography (OCT) findings to
      clinical examination, NFL and stereoscopic optic nerve head (ONH) photography,
      and Humphrey 24-2 visual fields. DESIGN: Cross-sectional prevalence study.
      PARTICIPANTS: The authors followed 19 patients in the study group and 14 patients
      in the control group. INTERVENTION: Imaging with OCT was performed
      circumferentially around the ONH with a circle diameter of 3.4 mm using an
      internal fixation technique. One hundred OCT scan points taken within 2.5 seconds
      were analyzed. MAIN OUTCOME MEASURES: Measurements of NFL thickness using OCT
      were performed. RESULTS: In most eyes with focal NFL defects, OCTs showed
      significant thinning of the NFL in areas closely corresponding to focal defects
      visible on clinical examination, to red-free photographs, and to defects on the
      Humphrey visual fields. Optical coherence tomography enabled the detection of
      focal defects in the NFL with a sensitivity of 65% and a specificity of 81%.
      CONCLUSION: Analysis of NFL thickness in eyes with focal defects showed good
      structural and functional correlation with clinical parameters. Optical coherence
      tomography contributes to the identification of focal defects in the NFL that
      occur in early stages of glaucoma.

PMID- 10080217
TI  - Visual outcome of surgery for epiretinal membranes with macular pseudoholes.
AB  - OBJECTIVE: To evaluate the effect of macular pseudohole on visual results after
      epiretinal membrane (ERM) surgery. DESIGN: Retrospective case-control study.
      PARTICIPANTS: The postoperative results for 50 eyes with ERMs combined with
      pseudohole were compared with the results for a paired series of idiopathic ERMs
      without pseudohole operated on during the same period. INTERVENTION: All patients
      underwent standard three-port pars plana vitrectomy, including core vitrectomy,
      and removal of the membrane. MAIN OUTCOME MEASURES: Anatomic and functional
      evaluations were performed before and after surgery. Main outcome measures were
      postoperative visual acuity and the persistence or disappearance of the
      pseudohole. RESULTS: For the patients with pseudohole, median preoperative visual
      acuity was 20/63 (range, 20/32-20/860) and median postoperative visual acuity was
      20/40 (range, 20/20-20/860). Vision improved by 2 or more lines in 31 (62%) of 50
      eyes. Forty eyes (80%) reached visual acuity of 20/50 or more. Pseudohole
      persisted in 22 eyes (44%) 3 months after surgery and in 15 eyes (30%) at 6
      months. There was no difference in visual acuity, whether or not the pseudohole
      persisted. For the patients without pseudohole, median preoperative visual acuity
      was 20/63 (range, 20/32-20/860). Median postoperative visual acuity was 20/40
      (range, 20/20-20/860). Vision improved by 2 or more lines in 37 eyes (74%). In 36
      eyes (72%), it was 20/50 or more. Neither preoperative nor postoperative visual
      acuity differed significantly in the groups with and without pseudohole.
      CONCLUSION: After surgery for idiopathic ERMs combined with pseudohole, visual
      outcome is good, and pseudohole has no adverse prognostic value. Pseudohole
      disappears inconstantly after surgery, but its persistence does not preclude good
      postoperative visual recovery.

PMID- 10080218
TI  - Central nervous system symptoms in patients with Behcet disease receiving
      cyclosporine therapy.
AB  - OBJECTIVE: To investigate the association between the development of central
      nervous system (CNS) symptoms in patients with Behcet disease and medical
      therapy. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 317
      patients with Behcet disease with ocular complications who visited Hokkaido
      University Hospital, Sapporo, Japan, between 1978 and 1994. MAIN OUTCOME
      MEASURES: The incidence of CNS symptoms in different medical therapies. RESULTS:
      Twenty-one (6.6%) of the 317 patients developed CNS symptoms, namely neuro-Behcet
      disease. Of the 21 patients, 12 were undergoing cyclosporine therapy. Of the 47
      patients who underwent cyclosporine therapy, 12 (25.5%) developed CNS symptoms,
      whereas only 9 (3.3%) of 270 patients who did not undergo cyclosporine therapy
      developed CNS symptoms. CONCLUSIONS: Cyclosporine in the treatment of Behcet
      disease appears to cause neurotoxicity or to accelerate the development of CNS
      symptoms. Thus, neurologic complications appear to represent a major side effect
      of cyclosporine in the treatment of patients with Behcet disease.

PMID- 10080219
TI  - Fluorophotometry in patients with human immunodeficiency virus with and without
      cytomegalovirus retinitis.
AB  - OBJECTIVE: To study the aqueous humor dynamics in subjects with human
      immunodeficiency virus (HIV) with and without cytomegalovirus (CMV) retinitis.
      DESIGN: Prospective cross-sectional study. PARTICIPANTS: Fourteen HIV-positive
      subjects (27 eyes, 19 with CMV retinitis and 8 without CMV retinitis), and a
      control group of 9 HIV-negative subjects (17 eyes). TESTING: Fluorophotometry.
      MAIN OUTCOME MEASURES: Aqueous flow rates as measured by fluorophotometry and
      intraocular pressure (IOP). RESULTS: Analysis of variance of the mean corrected
      aqueous flow rate revealed that both HIV-positive groups had significantly lower
      aqueous flow rates than did the control group (P < 0.03). No difference in mean
      aqueous flow rates was found between the HIV-positive eyes with or without CMV
      retinitis. Comparison of mean IOP revealed that HIV-positive eyes with CMV
      retinitis had significantly lower IOP than did the HIV-positive eyes without CMV
      retinitis (P = 0.03) and HIV-negative subjects (P = 0.002). There was no
      correlation between aqueous flow rate and IOP in HIV-positive subjects (P > 0.5).
      CONCLUSION: The lack of correlation between the aqueous flow rate and IOP
      suggests that there may be some disassociation between these parameters in HIV
      positive patients. Further studies are needed to better understand the mechanism
      of aqueous formation and in the management of disorders affecting IOP in this
      population.

PMID- 10080220
TI  - Pars planitis: clinical features and class II HLA associations.
AB  - OBJECTIVE: To describe a cohort of patients with pars planitis followed at a
      single tertiary care institution, determine the frequency of multiple sclerosis
      and/or optic neuritis in patients with this disorder, and calculate gene
      frequencies of human leukocyte antigen (HLA) class II alleles in these patients.
      DESIGN: Fifty-three patients with the diagnosis of pars planitis underwent
      clinical record review or telephone interview for follow-up or both; 32 of these
      underwent phlebotomy for analysis of HLA class II alleles. MAIN OUTCOME MEASURES:
      Outcomes included visual acuity, occurrence of multiple sclerosis and/or optic
      neuritis, and HLA class II gene frequencies. RESULTS: With a mean follow-up of 2
      years, approximately 90% of patients maintained a visual acuity better than 20/40
      in at least one eye. The most frequently encountered ophthalmic complications
      included cystoid macular edema, cataract, and epiretinal membrane formation. Of
      37 patients with pars planitis who had medical or neurologic follow-up
      evaluations, 6 (16.2%) developed multiple sclerosis. The HLA-DR15 allele, coding
      for one of the two HLA-DR2 subtypes, was associated with pars planitis (odds
      ratio = 2.86, 95% confidence interval = 1.42-5.78, P = 0.004). CONCLUSIONS: A
      common immunogenetic predisposition to multiple sclerosis and pars planitis may
      be associated with the HLA-DR15 allele. This association may represent genetic
      linkage to the HLA-DR locus or a role for the HLA-DR15 gene product in the
      pathogenesis of both of these diseases.

PMID- 10080221
TI  - Differentiation of degenerative retinoschisis from retinal detachment using
      optical coherence tomography.
AB  - OBJECTIVE: To assess the potential of optical coherence tomography (OCT) to
      differentiate retinoschisis from retinal detachment. Optical coherence tomography
      is a noninvasive, noncontact imaging method that produces high-resolution, cross
      sectional images of ocular tissue. DESIGN: Retrospective case series.
      PARTICIPANTS: Thirteen eyes of 12 patients with the differential diagnosis of
      retinoschisis versus retinal detachment. METHODS: Differentiation between
      retinoschisis and retinal detachment was established from both ophthalmoscopic
      and OCT examinations. MAIN OUTCOME MEASURE: Ability of OCT to differentiate
      retinoschisis from retinal detachment was measured. RESULTS: Thirteen eyes of 12
      patients with retinal elevation were examined with OCT. The cross-sectional view
      produced by OCT was effective in distinguishing retinoschisis from retinal
      detachment. Optical coherence tomography images of retinoschisis show a splitting
      of the neurosensory retina. The OCT images of retinal detachment show separation
      of full-thickness neurosensory retina from the retinal pigment epithelium band.
      The OCT images correlated with the clinical impression in all 13 cases.
      CONCLUSIONS: Based on this series of cases, OCT is a potentially useful new test
      that may be used to distinguish retinoschisis from rhegmatogenous retinal
      detachment.

PMID- 10080222
TI  - Palladium-103 plaque radiotherapy for choroidal melanoma: results of a 7-year
      study.
AB  - OBJECTIVE: To describe the first clinical experience with palladium-103 (103Pd)
      ophthalmic plaque radiotherapy for choroidal melanoma. DESIGN: Phase-I
      (nonrandomized) clinical trial. PARTICIPANTS: Eighty patients with uveal
      melanomas were diagnosed by clinical examination, found to be negative for
      metastatic disease, and offered 103Pd radioactive plaque treatment. Nine patients
      were concurrently treated with microwave hyperthermia. INTERVENTION: Palladium
      103 ophthalmic plaque radiotherapy was employed for each patient. Eye plaques
      were sewn to the episclera to cover the base of the intraocular tumor, radiation
      was continuously delivered over 5 to 7 days, and then the plaques were removed. A
      mean apical dose of 81 Gy was delivered. MAIN OUTCOME MEASURES: The authors
      evaluated the ease of use of 103Pd seeds within standard gold eye plaques.
      Patient-related outcomes were control of tumor growth, change in visual acuity,
      the development of radiation damage (retinopathy, optic neuropathy, and
      cataract), and metastatic disease. RESULTS: From September 1990 to December 1997,
      80 patients were treated with 103Pd and followed for an average of 38 months. Two
      patients were lost to follow-up. During this time, the authors found that 103Pd
      seeds were equivalent to iodine-125 (125I) with respect to plaque manufacture and
      ease of dosimetric calculations. Two patients in this series were treated for
      tumor recurrence after 125I plaque radiotherapy. They both failed secondary 103Pd
      treatment and were enucleated. When 103Pd was used as a primary treatment, it
      controlled the growth of 75 of 78 tumors (96%). Overall, there have been six
      enucleations: three failures of primary treatment, two failures of retreatment,
      and one for neovascular glaucoma. Visual acuity evaluations at the 36-month
      follow-up visit (including the enucleated patients) revealed that 38% of eyes had
      decreased 3 or more lines of vision, and 77% were 20/200 or better. CONCLUSION:
      Palladium-103 plaque radiotherapy can be used to treat uveal melanomas. Compared
      with 125I, computerized dosimetry suggests a more favorable dose distribution
      with 103Pd. Treatment of most patients resulted in tumor shrinkage and
      preservation of functional vision. The authors have noted no complications that
      might preclude the use of 103Pd ophthalmic plaque radiotherapy for choroidal
      melanoma.

PMID- 10080223
TI  - Iridocorneal melanoma associated with type 1 neurofibromatosis: a
      clinicopathologic study.
AB  - OBJECTIVE: A clinicopathologic study of an iridocorneal melanoma associated with
      type 1 (peripheral) neurofibromatosis is presented. DESIGN: Case report with
      clinicopathologic correlation. PARTICIPANT: A 32-year-old white woman with type 1
      neurofibromatosis presented with long-standing blindness of her right eye due to
      diffuse intrastromal brown corneal discoloration. INTERVENTION: The patient
      underwent penetrating keratoplasty and the corneal button was inspected. RESULTS:
      Histopathologic evaluation of the corneal button after penetrating keratoplasty
      revealed an intrastromal mixed-type malignant melanoma, which stained positively
      with HMB-45 and S-100 protein and spared the corneal epithelium and limbus. The
      corneal graft remained transparent, with best-corrected visual acuity of 20/30.
      Twenty-two months after surgery, the tumor involved the anterior chamber angle
      and the iris. Three years later, it caused refractory glaucoma necessitating
      enucleation. The iris tumor did not extend beyond the iris-lens diaphragm and
      showed the same cytologic features as the corneal stromal tumor. CONCLUSION: To
      our best knowledge, this is the first report of iridocorneal melanoma associated
      with peripheral neurofibromatosis. The location of the tumor in the deep corneal
      stroma, without initial macroscopic involvement of the angle or iris, may suggest
      that the corneal portion of the tumor may have developed "in situ" rather than as
      an extension of iris melanoma. The common origin of melanoma cells and Schwann
      cells from the neural crest and the proliferation of the Schwann cells in
      neurofibromatosis provides additional support for this hypothesis.

PMID- 10080224
TI  - Retinitis pigmentosa, nanophthalmos, and optic disc drusen: a case report.
AB  - OBJECTIVE: Although the associations of retinitis pigmentosa (RP) with
      nanophthalmos/microphthalmos and RP with optic disc drusen have previously been
      recognized, the concurrence of all three features, as far as the authors are
      aware, has not previously been reported. DESIGN: Case report. RESULTS: The
      authors report a sporadic case of nanophthalmos, RP, and optic nerve drusen with
      the additional complication of chronic angle closure glaucoma. CONCLUSIONS:
      Visual loss may be secondary to the complications of nanophthalmos, RP, or optic
      nerve drusen. Chronic angle closure may be caused by choroidal effusion with
      serous retinal detachment, which may, in turn, cause a pseudo-RP picture. It is
      therefore important to recognize the possible association of true RP with
      nanophthalmos as a cause for visual deterioration.

PMID- 10080225
TI  - A clinical and molecular genetic analysis of solitary ocular angioma.
AB  - OBJECTIVES: To determine whether ocular angioma can occur in the absence of von
      Hippel Lindau (VHL) syndrome, to define the clinical characteristics of sporadic
      (non-VHL) angioma, and to estimate a prevalence for sporadic ocular angioma.
      DESIGN AND PARTICIPANTS: A cross-sectional study of a cohort of patients with
      apparent sporadic ocular angiomatosis recruited from throughout the United
      Kingdom. INTERVENTION: Clinical details and a family history were obtained for
      the patients in the cohort. Systematic ocular examination and further systemic
      screening were performed on the patients and relatives when possible. Leukocyte
      DNA was examined for VHL germline mutations. MAIN OUTCOME MEASURES: Patients with
      solitary and typical VHL-like ocular angioma, without clinical and family
      histories for VHL, were selected as possible sporadic (non-VHL) ocular angioma
      cases. An estimate of the population prevalence of sporadic (non-VHL) ocular
      angioma was made from patients presenting in the East Anglian region of the
      United Kingdom over a 25-year period. RESULTS: From 32 patients referred, 17 had
      typical solitary ocular angioma and no evidence of other VHL complications in
      themselves or in family members. All 17 patients were negative for germline VHL
      mutations. The mean age of presentation was 30.9 years (median, 27.5; range, 3
      52); 11 of 17 eyes suffered visual loss and 4 of 17 tumors occurred on the optic
      disc. The estimated prevalence of non-VHL ocular angioma was 9.0 x 10(-6), 95%
      confidence interval (CI) = 3.3 - 19 x 10(-6) (1 in 110,000 persons, 95% CI = 1 in
      53,000-300,000). CONCLUSIONS: Sporadic ocular angioma can occur in the absence of
      VHL disease but appears less prevalently than VHL itself. The age of
      presentation, degree of visual morbidity, complications, morphology, and anatomic
      location of tumors are similar to those seen in VHL disease.

PMID- 10080226
TI  - Persistent hyperplastic primary vitreous with retinal tumor in tuberous
      sclerosis: report of a case including tumoral immunohistochemistry and
      cytogenetic analyses.
AB  - OBJECTIVE: The authors describe an ocular lesion combining the characteristics of
      persistent hyperplastic primary vitreous (PHPV) and a retinal tumor in an infant
      with tuberous sclerosis complex (TSC). STUDY DESIGN: Case report. METHODS:
      Immunohistochemistry and cytogenetic studies were performed on TSC cells from an
      intraocular tumor in a 6-week-old infant. RESULTS: Histopathologic examination
      showed a thick fibrovascular membrane between the aspect of the lens and the
      astrocytic component of the mass. Glial fibrillary acidic protein (GFAP) showed a
      variable intracytoplasmic reaction in the astrocytic proliferation, involving
      approximately 50% of the cells. Tissue culture studies showed a fairly rapid
      proliferation of fusiform cells, consistent with bipolar astrocytic cells.
      Cytogenetic studies showed one abnormal clone consisting of three hyperdiploid
      cells with a loss of chromosome 9 and a gain of chromosomes 6 and 12. CONCLUSION:
      The atypical localization of the retinal tumor could be explained by the fact
      that it was trapped during its proliferation by the retinal detachment associated
      with the PHPV.

PMID- 10080227
TI  - Vogt-Koyanagi-Harada syndrome after cutaneous injury.
AB  - OBJECTIVE: To describe three patients who developed Vogt-Koyanagi-Harada syndrome
      (VKH) after cutaneous injury. DESIGN: Retrospective case series. PARTICIPANTS:
      Three patients seen in the uveitis clinic at Aravind Eye Hospital and
      Postgraduate Institute of Ophthalmology, Madurai, India, participated. MAIN
      OUTCOME MEASURES: The history, evaluation, and management of the three patients
      were summarized. RESULTS: Three patients developed VKH syndrome shortly after
      cutaneous injury. In each case, the affected area of skin became vitiliginous on
      healing and simultaneous with the onset of ocular symptoms. One patient developed
      additional ectopic areas of vitiligo. All three patients developed chronic,
      bilateral, diffuse uveitis, one associated with an exudative retinal detachment
      and two with Dalen-Fuchs-like nodules. Well-recognized complications of VKH
      syndrome that occurred in the authors' patients included geographic atrophy of
      the retinal pigment epithelium (3 of 3), cataract (3 of 3), and glaucoma (1 of
      3). Ocular inflammation was well controlled in each patient with local or
      systemic corticosteroids or both. In one patient, the area of vitiligo showed
      increased pigmentation in response to systemic corticosteroid treatment.
      CONCLUSIONS: Vogt-Koyanagi-Harada syndrome may follow cutaneous injury,
      supporting the notion that this disorder may result from systemic sensitization
      to shared melanocytic antigens.

PMID- 10080228
TI  - Invasive giant cell astrocytoma of the retina in a patient with tuberous
      sclerosis.
AB  - OBJECTIVE: To report an unusual case of giant cell astrocytoma of the retina.
      DESIGN: Case report. INTERVENTION: A 10-month-old girl with tuberous sclerosis
      was found to have bilateral astrocytic hamartomas, the right eye being
      prominently involved by elevated and pedunculated lesions. At 7 years of age, she
      had posterior subcapsular cataract, retinal detachment, and subretinal exudation
      develop in the right eye. At 12 years of age, her blind, painful right eye had to
      be enucleated because of neovascular glaucoma and a spontaneous scleral
      perforation. RESULTS: Histopathologic examination showed that the entire vitreous
      cavity was filled with a mixture of tumor, granulation tissue, and necrotic
      debris. Part of the tumor was composed of spindle-shaped glial cells. The
      remainder was composed of large gemistocytic cells that contained large atypical
      nuclei and copious amounts of cytoplasm, which was intensely eosinophilic in some
      areas. The tumor contained foci of necrosis and rare mitotic figures. It had
      infiltrated the parenchyma of the retrolaminar nerve and extended to the surgical
      margin. Areas of unequivocal choroidal invasion were also identified. The tumor
      cells were intensely immunoreactive for neuron-specific enolase and S-100
      protein. In contrast, glial fibrillary acidic protein was only minimally
      positive. CONCLUSIONS: The histologic and immunohistochemical features of this
      retinal tumor resemble those of subependymal giant cell astrocytoma, a
      characteristic lesion in tuberous sclerosis. Although this unusual giant cell
      astrocytoma of the retina had atypical histopathologic features and local
      aggressive behavior, the systemic prognosis was excellent.

PMID- 10080229
TI  - Acute toluene induces biphasic changes in rat spontaneous locomotor activity
      which are blocked by remoxipride.
AB  - The behavioral hyperactivity elicited by most drugs of abuse has been linked to
      changes in mesolimbic dopamine neurotransmission. However, the locomotor
      stimulant effects of toluene, a constituent in many abused inhalants, has not
      been clearly associated with this site of action. The present study was designed
      to examine the hypothesis that toluene-induced hyperactivity is also dependent
      upon intact dopamine neurotransmission. Using photocell-equipped cages, 600-1200
      mg/kg toluene produced an inverted U-shaped dose response. However, in the
      presence of 5 mg/kg remoxipride, a selective D2-dopamine antagonist toluene
      induced hyperactivity was reduced by 57%. The effects of remoxipride appear to be
      selective as a pretreatment, as it did not reduce either spontaneous locomotor
      activity or the stimulatory effects of the muscarinic antagonist scopolamine.
      These results clearly show that toluene induces locomotor hyperactivity through a
      dopamine-dependent mechanism. Because the mesolimbic dopamine system has been
      shown to play a role in the rewarding properties of drugs of abuse, its
      activation by toluene may also underlie the abuse potential of this and other
      inhalants.

PMID- 10080230
TI  - The anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated
      plus-maze: a comparison with amphetamine.
AB  - Many abused substances have been found to possess anxiogenic-like or/and
      anxiolytic-like properties. Discrepancies about the effects of MDMA, one of the
      most popular recreational drugs in recent years, on anxiety have been seen in the
      literature, and almost all of the data in this respect were derived from
      retrospective studies. The present study was thus designed to examine the drug's
      actions by using an animal model of anxiety, the elevated plus-maze test in male
      mice. Intraperitoneal MDMA at 1 mg/kg was ineffective, at 4 mg/kg decreased the
      percent of open arm entries (p < 0.01), and increased enclosed entries (p <
      0.05), at 12 mg/kg had no significant effect, and at 20 mg/kg induced an increase
      of percent of open time (p < 0.01). As control drugs, amphetamine (0.5-4 mg/kg,
      i.p.) produced a dose-dependent, anxiogenic-like effect and diazepam (1 mg/kg,
      i.p.) induced an anxiolytic-like effect in the test. The results indicate that
      MDMA has anxiogenic-like properties at lower doses and anxiolytic-like at higher
      doses. The effects of MDMA and amphetamine on the mouse's responses to the plus
      maze are compared. These findings provide a possible explanation for the
      controversies over MDMA's effects on anxiety in the literature.

PMID- 10080231
TI  - Antipsychotic drugs and reproductive hormones: relationship to body weight
      regulation.
AB  - Excessive body weight gain is an undesirable side effect of prolonged
      administration of antipsychotic drugs (AP), which affects health and interferes
      with treatment compliance. It has been suggested that hyperprolactinemia-induced
      endocrine and metabolic abnormalities, particularly in the gonadal steroids,
      might be involved in the development of this type of weight gain. To test this
      hypothesis, reproductive hormones, cortisol, dehydro-epiandrosterone-sulfate
      (DHEA-S), thyroid hormones, and body weight gain were assessed in 18 patients (9
      men, 9 women) with mental disorders receiving AP who had been medication-free for
      at least 3 months before the study, and in 27 placebo-treated subjects (10 men,
      17 women). In women, hormones were evaluated during several phases of the
      menstrual cycle. A significant weight gain was observed in men but not in women.
      Under AP administration, women displayed significantly lower serum levels of
      estradiol and progesterone, whereas in men the levels of free testosterone and
      DHEA-S were significantly lower than in controls. Hyperprolactinemia was observed
      in both sexes. The levels of follicle-stimulating hormone in women and
      luteinizing hormone in men were significantly elevated by treatment, thus
      suggesting that the functioning of the hypothalamus-pituitary gonads was
      preserved. In men, such an endocrine profile resembles that observed in subjects
      with primary obesity. Women under AP administration were found to be relatively
      hyperandrogenic because of decreased serum estradiol levels, whereas women with
      primary obesity are known to display actual increased levels of androgens. These
      endocrine abnormalities may contribute to the excessive weight gain observed
      after AP treatment, and these could be the target of novel pharmacological
      treatments.

PMID- 10080232
TI  - Differences in central and peripheral responses to oxotremorine in young and aged
      rats.
AB  - Few studies have investigated the pharmacological response of agents that act on
      the cholinergic system from the point of view of age. The present article
      investigated central responses (tremor) and peripheral responses
      (chromodacryorrhea) subsequent to the administration of oxotremorine to young (3
      6 months of age) and aged rats (24-30 months of age). The aged rats presented
      greater duration and intensity of tremor in three doses utilized (0.25, 0.5, and
      1.0 mg/kg) compared to young rats. These two groups of animals did differ in
      latency for the onset of the tremor. The aged rats presented more intense
      chromodacryorrhea than the young rats in all utilized doses. These data are
      indicative that both responses--central and peripheral--are affected by aging,
      possibly as a result of pharmacokinetic alterations and/or alterations in
      functionality of the cholinergic system in aged rats.

PMID- 10080233
TI  - Antinociception elicited by aversive stimulation of the inferior colliculus.
AB  - We have shown that the inferior colliculus is involved in the integration of
      defensive reactions. Electrical and chemical stimulation of this structure
      elicits fear and escape behavior, expressed respectively by immobility (freezing)
      and wild running, followed by jumps. In this study, we analyzed whether the
      defensive behavior integrated at this level of the midbrain tectum is also
      followed by antinociception and its chemical mediation. In addition, we further
      addressed whether or not the aversive states and the stress-induced analgesia
      share the same neural substrates in the inferior colliculus. To this end, animals
      chronically implanted with a chemitrode, an electrode glued to a guide cannula,
      in the inferior colliculus were injected with naltrexone, methysergide,
      ketanserin, and midazolam. The animals were submitted to gradual increases in the
      electrical stimulation of the inferior colliculus, which allowed the measurement
      of the thresholds for aversive responses--vigilance, freezing, and escape.
      Following the induction of the aversive behavioral responses the animals were
      submitted to the tail-flick test. The results obtained show that midazolam was
      the only treatment that changed the aversive thresholds. On the other hand, while
      naltrexone and midazolam did not affect the fear-induced analgesia, it was
      inhibited by microinjections of the serotonergic blockers, methysergide and
      ketanserin. These results emphasize previous data demonstrating the nonopioid
      nature of the unconditioned analgesia to brain-aversive stimulation. Because
      methysergide is a nonspecific antagonist of 5-HT receptors, and ketanserin acts
      with a high degree of specificity at 5-HT2/5-HT1C receptors, the present results
      suggest that activation of 5-HT2/5-HT1C receptors may be implicated in the
      antinociception induced by stimulation of the inferior colliculus. Moreover, the
      present data also indicate that aversive reactions and analgesia from inferior
      colliculus stimulation can be pharmacologically dissociated.

PMID- 10080234
TI  - Acquisition and expression of conditioned hypoalgesia in morphine-naive and
      morphine-tolerant rats.
AB  - The present study used a within-subject design to examine acquisition and
      expression of conditioned hypoalgesia in 50 male Wistar rats. Morphine-naive rats
      preexposed to a heat stressor with saline were hypoalgesic when subsequently
      tested for latencies to tail flick or paw lick. However, morphine-tolerant rats
      preexposed to the heat stressor with saline failed to display hypoalgesia when
      tested for latencies to tail flick, but showed hypoalgesia when tested for
      latencies to paw lick. Taken together, these findings suggest that expression of
      conditioned hypoalgesic responses in morphine-tolerant rats may depend on the
      nociceptive test used. Both morphine-naive and morphine-tolerant rats preexposed
      to the heat stressor with morphine failed to display hypoalgesia on either the
      tail-flick or the hot-plate test, demonstrating that morphine's ability to block
      acquisition of conditioned hypoalgesia is independent of the test used to assess
      nociceptive sensitivity.

PMID- 10080235
TI  - The role of ventrolateral striatal acetylcholine in the production of tacrine
      induced jaw movements.
AB  - The anticholinesterase tacrine induces tremulous jaw movements in rats, and
      considerable evidence indicates that this response is dependent upon
      ventrolateral striatal mechanisms. Three experiments were conducted to study the
      relation between ventrolateral striatal acetylcholine and the production of
      tremulous jaw movements. In Experiment 1, intracranial microinjection of the
      acetylcholine synthesis inhibitor hemicholinium-3 into the ventrolateral
      neostriatum reduced tremulous jaw movements induced by 5.0 mg/kg tacrine.
      Microinjection of hemicholinium into a cortical site dorsal to striatum
      (Experiment 2) was without significant effect upon tacrine-induced tremulous jaw
      movements. In Experiment 3, rats were implanted with dialysis probes in the
      ventrolateral striatum to measure extracellular levels of acetylcholine during
      tacrine-induced jaw movements. Tacrine (2.5-5.0 mg/kg) increased both
      extracellular acetylcholine and tremulous jaw movements. The 5.0 mg/kg dose of
      tacrine produced a substantial increase in ventrolateral striatal acetylcholine
      levels (324% of baseline within 30 min). Across all tacrine-treated rats there
      was a significant linear correlation between tremulous jaw movements and
      acetylcholine levels (r = +0.56) during the first 30-min postinjection period.
      This correlation was largely due to the group that received 5.0 mg/kg tacrine;
      within this group, there was a very high correlation (r = +0.87) between
      tremulous jaw movements and acetylcholine levels in the first sample after
      injection. These data are consistent with the notion that tremulous jaw movements
      induced by tacrine are mediated by ventrolateral striatal acetylcholine.
      Moreover, these results suggest that dialysis methods could be used to monitor
      the relation between striatal acetylcholine and tremulous movements induced by a
      variety of different conditions.

PMID- 10080236
TI  - Classical conditioning during nitrous oxide treatment: influence of varying the
      interstimulus interval.
AB  - Classical conditioning of the rabbit nictitating membrane response (NMR) was
      accomplished by presenting a 75-ms tone conditioned stimulus (CS) at intervals of
      0, 100, 200, 400, and 800 ms before the presentation of a 100-ms shock
      unconditioned stimulus. Following every four paired trials (tone followed by
      shock), the occurrence of conditioned responses (CRs) was tested on every fifth
      trial in which only tone was presented (test trials). Three doses of nitrous
      oxide in oxygen (0, 33, and 67%) were used during conditioning. Nitrous oxide
      produced dose-dependent decrements of learning. Conditioned responding was
      related to the interstimulus interval (ISI) by a concave-down function. The
      higher dose of nitrous oxide caused more decrements of learning at several ISIs
      compared to the other two doses, changing the shape of the curve. Trace
      conditioning, which was examined in the present study, was more impaired under
      the influence of nitrous oxide than conditioning in a previous study, which used
      the standard delay paradigm. Thus, the drug impairs explicit memory more than
      implicit memory.

PMID- 10080237
TI  - The effects of d-amphetamine on intake of food and a sweet fluid containing
      cocaine.
AB  - Using a laboratory animal procedure designed to measure two aspects of
      reinforcement (self-administration and location preference), five adult rhesus
      monkeys each lived in three chambers: oral cocaine self-administration (0.26
      mg/kg/delivery cocaine hydrochloride in a sweet fluid) was specific to one end
      chamber, food self-administration was specific to the other end chamber, and no
      food cues or fluid cues were available in the middle chamber. Throughout the 10-h
      experimental day monkeys experienced multiple food, cocaine, and choice (food vs.
      sweet cocaine fluid), sessions. Oral d-amphetamine (AMPH; 0.5-1.5 mg/kg) or
      placebo was administered before the sessions to determine if this anorectic drug
      would differentially alter food and sweet cocaine fluid self-administration.
      Further, the effects of AMPH on the length of time a monkey spent in each
      chamber, when the stimulus cues indicating commodity availability were not
      present (location preference) were determined. AMPH produced dose-dependent
      decreases in both food and cocaine self-administration without affecting choice
      behavior. AMPH also increased the length of time monkeys spent in the food
      chamber, even when no stimuli indicating food availability were present. These
      results indicate that the relationship between self-administration and location
      preference measures of reinforcement is not completely concordant. The current
      procedure may prove useful in studying these two measures of reinforcement.

PMID- 10080238
TI  - Repeated cocaine exposure: effects on catecholamines in the nucleus accumbens
      septi of periadolescent animals.
AB  - Substance abuse is a major issue in today's society, and is an issue of critical
      importance in the adolescent population. Research indicates that substance use is
      often initiated during the adolescent period, and that brain reward areas are
      still undergoing changes during this time. Despite this, little research has
      investigated the effects of repeated drug use on the reward mechanisms of
      periadolescent animals. For this reason, the present study examined the effects
      of repeated cocaine administration on the responsiveness of the nucleus accumbens
      septi (NAcc) to either cocaine or saline challenge. The data indicate that
      repeated exposure to cocaine produces temporal shifts in the dopaminergic
      (DAergic) activity of the NAcc, with peak activity occurring earlier.
      Importantly, following repeated injections of cocaine, saline injections alone
      elicit increases followed by a subsequent suppression in DA overflow in the NAcc.
      These results suggest that the context of cocaine administration produces
      fundamental changes in the way that neurochemical reinforcement mechanisms
      respond. The expectancy of the drug alone elicits reward-related activity within
      the NAcc, which may play a critical role in the development of addiction.

PMID- 10080239
TI  - Thujone exhibits low affinity for cannabinoid receptors but fails to evoke
      cannabimimetic responses.
AB  - Absinthe, an abused drug in the early 1900s, has been speculated to activate the
      receptors responsible for marijuana intoxication (the CB1 cannabinoid receptor)
      (Nature 253:365-356; 1975). To test this hypothesis, we investigated oil of
      wormwood (Artemisia absinthium) the active plant product found in absinthe, and
      thujone, the active compound found in oil of wormwood. Radioligand receptor
      binding assays employing membrane preparations from rat brains containing CB1
      cannabinoid receptors, and human tonsils containing CB2 receptors, demonstrated
      that thujone displaced [3H]CP55940, a cannabinoid agonist, only at concentrations
      above 10 microM. HPLC analysis of oil of wormwood revealed that only the
      fractions having mobility close to thujone displaced [3H]CP55940 from the CB1
      cannabinoid receptor. [35S]GTPgammaS binding assays revealed that thujone failed
      to stimulate G-proteins even at 0.1 mM. Thujone failed to inhibit forskolin
      stimulated adenylate cyclase activity in N18TG2 membranes at 1 mM. Rats
      administered thujone exhibited different behavioral characteristics compared with
      rats administered a potent cannabinoid agonist, levonantradol. Therefore, the
      hypothesis that activation of cannabinoid receptors is responsible for the
      intoxicating effects of thujone is not supported by the present data.

PMID- 10080240
TI  - Rotational behavior in dopamine nigrostriatal denervated rats: effects of a wide
      range of time intervals between apomorphine administrations.
AB  - Previous studies using the turning behavior animal model have shown both
      increases and decreases in rotational behavior following successive
      administrations of dopamine agonists. To clarify the results obtained with this
      model, we studied the variability of rotational behavior after repeated
      challenges with low doses of apomorphine (0.05 mg/kg) at different time intervals
      ranging between 2 h and 14 days. Results show a decrease in the total number of
      turns with time intervals of 2, 6, and 12 h between administrations, and an
      increase in the total number of turns when apomorphine was administered once
      every 24 h. In contrast, when animals were tested at 7- and 14-day intervals, a
      stable number of turns in successive challenges was obtained. These results
      suggest that when successive injections of dopamine agonists are administered at
      sufficiently long intervals of time, the neuroadaptations that take place due to
      repeated drug exposure may not be apparent. These findings are relevant for the
      design of future experiments using this model.

PMID- 10080241
TI  - CCK(A) and 5-HT3 receptors interact in anorectic responses to amino acid
      deficiency.
AB  - Serotonin3 (5-HT3) receptors in the periphery mediate anorectic responses to the
      amino acid deficiency, which occurs after eating amino acid-imbalanced diets
      (IMB). However, other neurochemical systems, notably cholecystokinin (CCK), are
      known to affect food intake. We pretreated rats systemically with tropisetron, a
      5-HT3 receptor antagonist, alone and combined with antagonists of CCK(A) and
      CCK(B) receptors, and measured intake of an IMB. Devazepide, a CCK(A) receptor
      antagonist, appeared to interact with tropisetron in the anorectic responses to
      IMB, blunting the usual remediation of IMB anorexia by tropisetron. The CCK(B)
      receptor antagonist, L-365, 260, increased intake of both IMB and an amino acid
      balanced basal diet (BAS) and did not interact with tropisetron. Our data suggest
      that activation of CCK(A) receptors is interactive with 5-HT3 receptor activity
      in mediating IMB anorexia in the aminoprivic feeding model.

PMID- 10080242
TI  - DA1 receptor activity opposes anorectic responses to amino acid-imbalanced diets.
AB  - The serotonin3 (5-HT3) receptor plays an important role in the aminoprivic
      feeding model. Other neurochemical systems, including cholecystokinin (CCK) and
      dopamine (DA), are known to affect food intake. We pretreated rats systemically
      with tropisetron, a 5-HT3 receptor antagonist, alone and combined with
      antagonists of DA1 and DA2 receptors, and measured intake of an amino acid
      imbalanced diet (IMB). As expected, tropisetron significantly increased intake of
      IMB. SCH-23390, a DA1 antagonist, increased IMB anorexia. When combined with
      tropisetron, DA2 antagonism with eticlopride reduced short-term intake of both
      the basal diet (BAS) and IMB. In the IMB model, specificity of 5-HT3-DA2
      interactions, and of 5-HT3-CCK(A) interactions from previous studies, prompted
      investigation of CCK(A)-DA2 interactions; there appeared to be none. SKF-38393, a
      DA1 agonist, combined with the CCK(A) receptor antagonist, devazepide, increased
      BAS and tended to increase IMB intake. Thus, CCK(A)-DA1 interactions were not
      specific for IMB. These data suggest that DA1 receptor activity opposes IMB
      anorexia, possibly via an interaction with the 5-HT3 receptor.

PMID- 10080243
TI  - Antiaggresive and anxiolytic effects of gepirone in mice, and their attenuation
      by WAY 100635.
AB  - The purpose of the investigation was to ascertain whether (a) the antiaggressive
      effects of the 5-HT1A partial agonist, Gepirone, could be mediated via its
      anxiolytic action; (b) the selective 5-HT1A antagonist, WAY 100635, reversed
      these effects, and (c) the modulation of "stress hyperthermia" could be
      attributed to direct effects of the drugs. Isolated male mice were treated with
      WAY 100635 (0, 1.5, 2.5, and 5 mg/kg) given 15 min prior to Gepirone (0, 2.5, 5,
      and 7.5 mg/kg). Rectal temperature was taken before the first injection and again
      prior to the behavioral tests. In the first session only, subjects were tested
      for anxiety on the elevated plus-maze before the resident-intruder test. Gepirone
      reduced aggression in a dose-dependent manner. This effect was counteracted by
      all doses of WAY 100635. On the elevated plus maze, Gepirone increased open-arm
      entries and duration and reduced risk assessment. The largest dose of WAY 100635
      had a mild direct anxiolytic action, but all doses reduced the anxiolytic action
      of the largest dose of Gepirone. Body temperature was decreased dose dependently
      by Gepirone, an effect prevented by WAY 100635. The results justify attributing
      the involvement of the 5-HT1A receptors in the modulation of aggression and
      anxiety.

PMID- 10080244
TI  - Temporal oscillations of serum electrolytes in N-phthaloyl GABA-treated rats.
AB  - N-Phthaloyl gamma-aminobutyric acid (P-GABA) has been known to cross the blood
      brain barrier and ultimately to increase brain GABA level. In the present study,
      P-GABA was administered to Wistar rats for 21 days and circadian rhythms of
      sodium, potassium, and calcium levels in serum were studied under seminatural
      light-dark conditions. P-GABA administration caused desynchronization of the
      rhythms and advanced the peak times of serum electrolytes. Exogenously
      administered P-GABA could alter the photic information received by the clock. The
      results could be explained by slightly less or more than 1-h daily delays, which
      would bring the peak times to the points 21 days after the start of
      administration. The changes in amount of electrolytes after P-GABA administration
      are discussed.

PMID- 10080245
TI  - Ethopharmacological analysis of 5-HT ligands on the rat elevated plus-maze.
AB  - The present study investigated the behavioral effects of five 5-HT agonists and
      antagonists in the rat elevated-plus-maze using conventional and ethologically
      derived measures. An anxiolytic effect of the 5-HT1A agonist ipsapirone (0.25,
      0.75, and 2.25 mg/kg) was detected by risk-assessment and scanning but not by
      percentage of open-arm entries and time spent on open arms. Anxiogenic effects of
      the 5-HT2C agonist TFMPP (0.1, 0.2, and 0.4 mg/kg) and 5-HT2A antagonist SR
      46349B (1, 3, and 10 mg/kg) were detected by percentage of open-arm entries, time
      spent on open arms, scanning, end exploring, but not by risk assessment. Finally,
      the effects of the 5-HT3 antagonist BRL 46470 A (0.001, 0.01, and 0.1 mg/kg) and
      5-HT(2A/C) antagonist RP 62203 (0.25, 1, and 4 mg/kg) were scarce in both
      conventional and ethologically derived measures. These results are indicative
      that ethological measures may sometimes be more sensitive than the standard ones,
      and should be used together with them when assessing serotonergic or any other
      novel drugs in the elevated plus-maze.

PMID- 10080246
TI  - Behavioral and immunological effects of exogenous butyrylcholinesterase in rhesus
      monkeys.
AB  - Although conventional therapies prevent organophosphate (OP) lethality,
      laboratory animals exposed to such treatments typically display behavioral
      incapacitation. Pretreatment with purified exogenous human or equine serum
      butyrylcholinesterase (Eq-BuChE), conversely, has effectively prevented OP
      lethality in rats and rhesus monkeys, without producing the adverse side effects
      associated with conventional treatments. In monkeys, however, using a commercial
      preparation of Eq-BuChE has been reported to incapacitate responding. In the
      present study, repeated administration of commercially prepared Eq-BuChE had no
      systematic effect on behavior in rhesus monkeys as measured by a six-item serial
      probe recognition task, despite 7- to 18-fold increases in baseline BuChE levels
      in blood. Antibody production induced by the enzyme was slight after the first
      injection and more pronounced following the second injection. The lack of
      behavioral effects, the relatively long in vivo half-life, and the previously
      demonstrated efficacy of BuChE as a biological scavenger for highly toxic OPs
      make BuChE potentially more effective than current treatment regimens for OP
      toxicity.

PMID- 10080247
TI  - Intrathecal oxotremorine affects formalin-induced behavior and spinal nitric
      oxide synthase immunoreactivity in rats.
AB  - The present research was undertaken to investigate, by behavioral and
      immunohistochemical methods, the effects of intrathecal (i.th.) injection of the
      muscarinic agonist oxotremorine on the response to the long-lasting nociceptive
      stimulus induced by injection of formalin into the rat hind paw. Formalin
      injection induced a biphasic, pain-induced behavioral response (paw jerks), as
      well as an increase in the number of nitric oxide (NO) synthase-labeled neurons
      in laminae I-III, IV, and X, but not in laminae V-VI. Oxotremorine (0.1-10 ng,
      i.th.) inhibited paw-jerk frequency in both phases of formalin-induced behavior.
      The immunohistochemical results showed that i.th.-injected oxotremorine
      differently affected the level of NO synthase in lumbar part of the spinal cord:
      no change or increase after the dose of 1 ng, and a significant reduction of
      nitric oxide synthase neurons after the higher dose (10 ng). These results
      evidenced a role of cholinergic system in the modulation of tonic pain and in
      nitric oxide synthase expression at the spinal cord level, which further suggests
      that these two systems could be involved in phenomena induced by long-lasting
      nociceptive stimulation.

PMID- 10080248
TI  - Dextromethorphan attenuates ethanol withdrawal syndrome in rats.
AB  - The effects of dextromethorphan (DM), a noncompetitive antagonist of the N-methyl
      D-aspartate (NMDA) receptors, have been investigated on ethanol withdrawal signs
      in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM
      (10, 20, and 40 mg/kg) and saline were injected intraperitoneally at the third
      hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also
      administered to ethanol naive rats. DM (40 mg/kg) did not produce any significant
      change in locomotor activity in ethanol naive rats. The effects of DM on
      locomotor activity and total ethanol withdrawal score were evaluated at the
      fourth and sixth hours of ethanol withdrawal. DM inhibited locomotor
      hyperactivity at these periods. DM also reduced total ethanol withdrawal score
      from the fourth hour to the sixth hour, and it significantly decreased audiogenic
      seizures. Seizure susceptibility after chronic ethanol exposure may be dependent
      upon sensitization or upregulation of NMDA processes and NMDA receptors. Our
      results suggest that inhibition of NMDA receptors by DM alleviates signs of
      ethanol withdrawal.

PMID- 10080249
TI  - The discriminative stimulus properties of EGb 761, an extract of Ginkgo biloba.
AB  - Stimulus control was established in a group of nine rats using a dose of EGb 761
      of 10 mg/kg, administered i.p., 15 min before training. A two-lever operant task
      using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based
      upon a criterion for the presence of stimulus control of five consecutive
      sessions during which 83% or more of all responses were on the appropriate lever,
      a mean of 24 sessions was required to reach criterion performance. Subsequently,
      it was observed that EGb 761-induced stimulus control is significantly
      antagonized by the selective 5-HT1A antagonist WAY-100635, but is unaffected by
      the 5-HT2 antagonist pirenperone. Furthermore, EGb 761 generalized to the
      selective 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin [8-OH-DPAT], and this
      generalization was blocked by WAY-100635. The present results indicate that EGb
      761 is able to induce stimulus control when administered via the intraperitoneal
      route, and that its stimulus effects are mediated in part by activity at the 5
      HT1A receptor.

PMID- 10080250
TI  - Behavioral effects of AR-R 15849, a highly selective CCK-A agonist.
AB  - The behavioral effects of AR-R 15849, a novel cholecystokinin agonist with high
      affinity and selectivity for the CCK-A receptor subtype, were examined.
      Initially, using an operant feeding paradigm to test for anorectic activity and
      specificity, acute administration of AR-R 15849 was found to alter the intake and
      pattern of feeding in a manner similar to prefeeding. Further, AR-R 15849 did not
      induce compensatory feeding as did CCK-8, and did not affect performance on
      running rates of responding, or motor activity on a running wheel, as did
      fenfluramine. In tests for subchronic anorectic activity, daily intraperitoneal
      injections of AR-R 15849 significantly reduced food intake in fasted rats over a
      9-day test period with greater efficacy compared to its nonselective predecessor
      AR-R 14294 (formerly FPL 14294). The sustained decrease in food intake with AR-R
      15849 treatment resulted in a significant reduction in body weight gain over 9
      days. Finally, an experiment designed to determine the effect of caloric
      deprivation and subchronic drug exposure on the overall efficacy of AR-R 15849
      indicated that pharmacological tolerance does not develop following subchronic
      treatment.

PMID- 10080251
TI  - Effects of dizocilpine (MK-801) on flash-evoked potentials, body temperature, and
      locomotor activity of hooded rats.
AB  - The present study examined the effects of Dizocilpine (MK-801; a noncompetitive N
      methyl-D-aspartate receptor antagonist) on flash-evoked potentials recorded from
      both the visual cortex (VC) and superior colliculus (SC) of chronically implanted
      hooded rats. The potentials were recorded at 5, 20, and 35 min following i.p.
      injections of saline, and of 0.1, 0.3, and 1.0 mg/kg MK-801 on separate days. The
      amplitude of VC component P1 was unaltered following drug treatment. N1 was
      increased in amplitude by the 0.1-, 0.3-, and 1.0-mg/kg doses, while two other
      negative peaks in the VC emerged, beginning with the 0.1-mg/kg dose, to
      complicate the waveform. One negative peak developed between N1 and P2, while the
      other effectively split peak P2 (forming P2A and P2B). P2A was depressed at all
      doses, while P2B was depressed at 0.1 mg/kg but augmented at the 1.0-mg/kg dose.
      N2 was elevated by the 0.3- and 1.0-mg/kg doses, while P3 was increased in
      amplitude by all doses. N3 was transiently enhanced by the 0.3-mg/kg dose. SC
      amplitudes were less affected, with P3 and N4 reduced in amplitude by the 0.3-
      and 1.0-mg/ kg doses. The latencies of most components in both structures were
      decreased, often with all doses, but generally at the later recording times. A
      second experiment demonstrated significant MK-801-induced hyperthermia at all of
      the above doses, although a higher dose of 3.0 mg/kg MK-801 caused hypothermia.
      The reduction in component latencies may, therefore, result at least in part from
      a drug-induced hyperthermia. A third experiment demonstrated MK-801-induced
      changes in locomotor activity in rats in an open field. The effects were both
      dose and time dependent. The 0.3-mg/kg dose of MK-801 produced significant
      increases in the number of line crossings from 20-60 min in comparison to the
      saline condition. Increases in the number of line crossings with the 1.0-mg/kg
      dose peaked at 15 min, and then gradually declined. It is unlikely, however, that
      these changes in movement can account for the effects of MK-801 on evoked
      potentials. In conclusion, the results show that blockade of the ion channel
      associated with the NMDA receptor produces profound changes in the activity of
      the neural pathways that are reflected in the middle components of the flash
      evoked potential recorded from the VC.

PMID- 10080252
TI  - TRH in therapeutic vs. nontherapeutic seizures: affective and motor functions.
AB  - We have modeled some aspects of electroconvulsive therapy (ECT) in rats. In
      addition to sham-treated controls, one group received two electroconvulsive (ECS)
      current-doses at grand mal seizure threshold. Two more groups received three
      additional ECSs at two higher current-doses. Only the two suprathreshold groups
      showed significant antidepressant (AD) effects in the forced-swim test, but all
      three seizure groups showed significant increases in TRH and related peptides in
      anterior cortex (AC), pyriform cortex (PYR), amygdala/entorhinal cortex (AY), and
      hippocampus (HC). In motor cortex (MC), TRH appeared to be increased only in the
      lower dose suprathreshold ECS condition. No condition increased TRH in striatum
      (STR). These results fell short of directly implicating limbic TRH in AD effects,
      but in HC, MC, and STR, correlations of peptide levels with individual swim
      scores raise the possibility that this peptidergic system might be involved in
      motor as well as affective functions. Other peptides related to TRH might also be
      implicated in affective regulation and antidepressant effects.

PMID- 10080253
TI  - The psychiatric diagnoses of twenty-two adolescents who have sexually molested
      other children.
AB  - The purpose of this study was to assess the prevalence of specific psychiatric
      disorders in adolescents who have sexually molested other children. Twenty-two
      adolescent males (aged 13 to 17 years) who sexually molested a child at least
      once were evaluated with structured clinical interviews for DSM-III-R axis I
      disorders. All subjects met lifetime DSM-III-R criteria for pedophilia (with the
      exception of the age requirement), 21 (95%) for two or more paraphilias, 18 (82%)
      for a mood disorder (12 [55%] for a bipolar disorder), 12 (55%) for an anxiety
      disorder, 11 (50%) for a substance use disorder, and 12 (55%) for an impulse
      control disorder. Also, 12 (71%) of 17 subjects were diagnosed with attention
      deficit/hyperactivity disorder, and 16 (94%) with conduct disorder. We conclude
      that some adolescent child molesters may have pedophilia or other paraphilias.
      Other axis I disorders with impulsive features, especially conduct, attention
      deficit/hyperactivity, bipolar, and substance use disorders, may also be found in
      these adolescents.

PMID- 10080254
TI  - Pseudologia fantastica and factitious disorder: review of the literature and a
      case report.
AB  - Pseudologia fantastica is sparsely defined in the psychiatric literature, and has
      not been reviewed in the English-language psychiatric literature since 1988. To
      redefine the role of pseudologia fantastica in factitious disorder, the case of a
      56-year-old man with factitious disorder is discussed.

PMID- 10080255
TI  - Premorbid risk factors for violence in adult mental illness.
AB  - The role of premorbid factors in the violence associated with adult mental
      illness has received little attention. We previously found that the premorbid
      onset of substance abuse in early adolescence or childhood was a more powerful
      predictor of violence in adult patients with chronic mental illness than comorbid
      substance abuse. In the present study, we retrospectively assessed patients with
      chronic mental illness for a history of childhood conduct disorder. Consecutive
      referrals to a community treatment team were evaluated with a standardized
      protocol that included questions about violent behavior. Patients who met DSM-IV
      criteria for a primary diagnosis of major axis I disorder (N = 64) were assessed
      for behavior prior to age 15 with a checklist for DSM-IV criteria of conduct
      disorder using self-report data, supplemented by collateral information from
      charts and relatives when possible. About half of the sample had a history of
      committing violent acts in the community, and 26% met criteria for childhood
      conduct disorder. The odds of violence in adulthood was 10-fold higher for
      subjects with a history of childhood conduct disorder. Not surprisingly, there
      was considerable overlap between conduct disorder and early-onset substance
      abuse. About half of the patients with a history of substance abuse prior to age
      15 also had a history of conduct disorder. However, these two premorbid
      conditions appear to be at least partially independent in predicting adult
      violence in this population.

PMID- 10080256
TI  - Female psychoactive substance-dependent suicide victims differ from male--results
      from a nationwide psychological autopsy study.
AB  - Suicides involving alcohol or other substance dependence have been studied in
      male-dominated populations. We studied male and female suicide victims with DSM
      III-R psychoactive substance dependence (PSD) separately in a nationwide
      psychological autopsy study in Finland. The subjects were substance-dependent
      males from a systematic random sample and all substance-dependent female suicide
      victims from the total population of suicides committed over a 1-year period in
      Finland. Comparisons by sex and age were made, and two logistic models were
      created predicting sex. Females were more likely to have abused or been dependent
      on prescribed medication. Female victims aged 40 years or less had a relatively
      high frequency of borderline personality disorder (BPD), frequent previous
      suicide attempts, and suicidal communication, whereas older females were more
      like older males. The onset of a comorbid axis I disorder preceded substance
      dependence more often among females. Male and female substance-dependent suicide
      victims differ in a number of characteristics, including previous suicidality,
      age-related variation in personality disorders, and type of substance used.
      Findings from studies of predominantly male substance-dependent suicide victims
      cannot necessarily be generalized to females.

PMID- 10080257
TI  - Correlates of problem drinking among young Japanese women: personality and early
      experiences.
AB  - Problem drinking patterns were measured by the CAGE questionnaire among 90
      currently drinking young Japanese women who were recently recruited by a Japanese
      company. Problem drinking was examined in terms of personality (temperament and
      character as defined by Cloninger) and early life experiences (perceived parental
      behavior, parental abusive behavior, being bullied at school, and positive and
      negative life events experienced before the age of 16). Multiple regression
      analysis revealed that problem drinking could be predicted by a set of
      personality scores, early death of a close friend, and the interaction of the
      death of a close friend and low explorative excitability (novelty-seeking
      component 1). This suggests that problem drinking in young women is partly
      determined by both personality and negative life events during childhood.

PMID- 10080258
TI  - Flashbulb memories and other repetitive images: a psychiatric perspective.
AB  - The term "flashbulb memory" was used by Brown and Kulik in 1977 to refer to the
      vivid recollections that humans may have of events considered to be of particular
      significance to the individual or group. These memories are described as having a
      photographic quality and as being accompanied by a detail-perfect apparel of
      contextual information (weather, background music, clothes worn, etc.) pertaining
      to the time and place where the event was first known. They may even evoke
      emotions similar to the ones felt upon hearing the news. It has been suggested
      that flashbulb memories are formed by the activity of an ancient brain mechanism
      evolved to capture emotional and cognitive information relevant to the survival
      of the individual or group. Some of the original assumptions made by Brown and
      Kulik have since been challenged, but the phenomenon in question remains an
      important area of research. However, the latter is often marred by the fact that
      flashbulb memories are studied as if they were unique psychological events
      without parallel in clinical practice. Psychiatrists, however, should consider
      flashbulb memories as being members of a broad family of experiences that include
      drug flashbacks, palinopsia, palinacusis, posttraumatic memories, and the vivid
      and haunting memories experienced by subjects with some forms of mental disorder
      (e.g., phobias, panic attacks, obsessional disorder, phantom-limb phenomena, and
      depressive melancholia). All of these experiences share clinical features such as
      paroxysmal repetition, sensory vividness, a capacity to trigger emotions,
      dysphoria, and a tendency for the rememberer to shift from the role of actor to
      that of observer and for the reminiscence to become organized in a stereotyped
      narrative. Some of these clinical phenomena are discussed, and the suggestion is
      made that seeking phenomenological and neurobiological common denominators to all
      of these experiences may be a superior research strategy versus studying
      flashbulb memories alone.

PMID- 10080259
TI  - Human immunodeficiency virus-related risk behavior among Italian psychiatric
      inpatients.
AB  - This study evaluated at-risk behavior for human immunodeficiency virus (HIV)
      infection among Italian psychiatric inpatients. One hundred patients with mental
      disorders consecutively admitted to an acute psychiatric unit over a 1-year
      period were studied using a self-report questionnaire. In these patients, 53.1%
      reported sex with multiple partners, 35.4% with occasional partners, 57% with
      prostitutes, and 6.7% with intravenous (i.v.) drug users (i.v.DUs). Forty-three
      percent never used condoms during sexual intercourse, 23% used drugs
      intravenously, and 20% shared needles. Only one third of the patients were tested
      for HIV, and two tested seropositive ([HIV+] prevalence, 5.8%). Most patients
      (62%) reported no concern about the risk of HIV infection. The rate of HIV risk
      behaviors was higher among psychiatric patients versus a control group of 90
      healthy people. These findings indicate an alarming rate of HIV risk behaviors
      among Italian psychiatric inpatients and the need for closer attention to HIV
      assessment and education in mental health settings.

PMID- 10080260
TI  - Insight in psychosis: an elusive target.
AB  - Insight is a quality which has been highly valued by most clinicians in the
      mental health field, largely because a strong link is assumed between good
      insight and better quality of life. Yet it is a complex construct, one which has
      not until recently been subjected to much critical scrutiny or adequately
      explicated. All too often, particularly in the field of psychosis, the term has
      been used as shorthand for the degree of congruence between the explanatory
      models and views on the mode and conditions of treatment of the clinician and the
      patient. Conflicts about these matters are ubiquitous in the care of psychotic
      patients. Recently, there has been a recognition that there are a number of
      dimensions to the construct, and that some of these relate to differences in
      attributional perspective. This has opened up the issue to more sophisticated
      research drawing on established but untapped psychological and neurobiological
      theories, and has formed a better framework for the development of more effective
      research and therapeutic strategies.

PMID- 10080261
TI  - Factor analysis of delusional disorder symptomatology.
AB  - Delusional disorder symptomatology has been poorly investigated with factor
      analytic studies. Most attempts to identify its symptomatologic structure were
      made with schizophrenic or mixed psychotic populations and included only
      delusional symptoms. The purpose of this study was to analyze the whole
      symptomatologic structure of delusional disorder. One hundred eight inpatients
      with delusional disorder (DSM-III-R) were evaluated for lifetime symptoms using
      the Operational Criteria (OPCRIT) checklist for psychotic illness and included in
      a factorial analysis. Four factors were evaluated: (1) core depressive symptoms,
      (2) hallucinations, (3) delusions, and (4) irritability symptoms. Thus, when
      scored by the OPCRIT checklist, delusional symptomatology consisted of four
      independent factors, indicating a substantial heterogeneity of this diagnostic
      category.

PMID- 10080262
TI  - Selegiline augmentation of antipsychotics for the treatment of negative symptoms
      in schizophrenia.
AB  - This case series describes three patients with a DSM-IV diagnosis of
      schizophrenia attending a continuing day treatment (CDT) program. They showed
      significant improvement in negative symptoms and overall functioning after the
      addition of selegiline to the antipsychotic regimen. No side effects were
      observed with this combination.

PMID- 10080263
TI  - Frequency of dissociative identity disorder in the general population in Turkey.
AB  - This study attempted to determine the prevalence of dissociative identity
      disorder in the general population. The Dissociative Experiences Scale (DES) was
      administered to 994 subjects in 500 homes who constituted a representative sample
      of the population of Sivas City, Turkey. The mean DES score was 6.7+/-6.1 (mean
      +/- SD). Of the 62 respondents who scored above 17 on the DES, 32 (51.6%) could
      be contacted during the second phase of the study. They were matched for age and
      gender with a group of respondents who scored below 10 on the scale, and the
      Dissociative Disorders Interview Schedule (DDIS) was then administered to both
      groups. Seventeen subjects (1.7%) received a diagnosis of dissociative disorder
      according to the structured interview. In the third phase, eight of 17 subjects
      who had a dissociative disorder on the structured interview could be contacted
      for a clinical evaluation. They were matched with a nondissociative control group
      and interviewed by a clinician blind to the structured interview diagnosis. Four
      of eight subjects were diagnosed clinically with dissociative identity disorder,
      yielding a minimum prevalence of 0.4%. Dissociative identity disorder is not rare
      in the general population. Self-rating instruments and structured interviews can
      be used successfully for screening these cases. Our data, derived from a
      population with no public awareness about dissociative identity disorder and no
      exposure to systematic psychotherapy, suggest that dissociative identity disorder
      cannot be considered simply an iatrogenic artifact, a culture-bound syndrome, or
      a phenomenon induced by media influences.

PMID- 10080264
TI  - Dissociative detachment and memory impairment: reversible amnesia or encoding
      failure?
AB  - The authors propose that clinicians endeavor to differentiate between reversible
      and irreversible memory failures in patients with dissociative symptoms who
      report "memory gaps" and "lost time." The classic dissociative disorders, such as
      dissociative amnesia and dissociative identity disorder, entail reversible memory
      failures associated with encoding experience in altered states. The authors
      propose another realm of memory failures associated with severe dissociative
      detachment that may preclude the level of encoding of ongoing experience needed
      to support durable autobiographical memories. They describe how dissociative
      detachment may be intertwined with neurobiological factors that impair memory,
      and they spell out the significance of distinguishing reversible and irreversible
      memory impairment for diagnosis, patient education, psychotherapy, and research.

PMID- 10080265
TI  - Application of double voxel functional spectroscopy to event-related cognitive
      experiments.
AB  - The hemodynamic response to functional activation can be regarded as the
      convolution of the neuronal response with an unknown kernel. As such, it
      introduces an intrinsic blurring that limits the attainable temporal resolution
      of functional magnetic resonance (fMR) techniques. This study demonstrates that
      by measurement of displacements in activation onsets between different types of
      trial, it is nevertheless possible to obtain a subsecond temporal accuracy in
      fMR. A single trial stimulation paradigm was adopted: a simple search task
      embedded in a longer period of visual flicker stimulation that produced reliable
      activations in the primary visual cortex and supplementary motor area. Data were
      acquired from both of these regions using double voxel functional spectroscopy.

PMID- 10080266
TI  - Selection of high-definition 2D virtual profiles with multiple RF pulse
      excitations along interleaved echo-planar k-space trajectories.
AB  - A method for spatially selective excitation of 2D RF profiles is reported. The
      method makes use of multiple shots to traverse interleaved echo-planar
      trajectories in 2D k space during each RF pulse excitation. Results from each of
      the interleaved excitations are summed, with the net effect being the excitation
      of a virtual profile. The method allows for the excitation of high-definition 2D
      profiles with standard gradient hardware. Signal to noise is enhanced by a factor
      equal to the square root of the number of interleaved excitations, compared with
      a single-shot excitation. Potential applications for volume-localized
      spectroscopy, functional MRI, and high-resolution reduced-field-of-view imaging
      are discussed.

PMID- 10080267
TI  - Submillimeter functional localization in human striate cortex using BOLD contrast
      at 4 Tesla: implications for the vascular point-spread function.
AB  - Using multislice segmented echoplanar imaging at 4 T, we have measured an upper
      bound to the cortical vasculature point-spread function (PSF) using functional
      magnetic resonance imaging (fMRI) in humans. Our experiments demonstrate that
      cortical subunits that are approximately 700 microm apart can be resolved using
      the early part of the hyperoxygenation phase of the blood oxygenation level
      dependent (BOLD) effect. This was accomplished using brief (4 sec) single trials
      of monocular and binocular stimulation of ocular dominance columns in human
      primary visual cortex. The data suggest that at even higher magnetic fields, the
      cortical vasculature PSF may be limited by the extent and nature of horizontal
      connections and not signal-to-noise ratio.

PMID- 10080268
TI  - In vivo measurement of ADC change due to intravascular susceptibility variation.
AB  - The apparent diffusion coefficient (ADC) of extravascular tissue water in rat
      brains was measured in response to step-wise injections of the superparamagnetic
      intravascular contrast agent AMI-227. These data were normalized and compared
      with measured changes in R2* and blood magnetic susceptibility. Linear regression
      showed that ADC changes 33%/ppm shift of intravascular susceptibility and 0.43%
      s(-1) change in R2*. These changes correspond to a predicted ADC change of
      approximately 6% for a change between fully oxygenated and fully deoxygenated
      blood. The source of these ADC changes was confirmed to be background gradients
      within the sample by the use of diffusion weighting with bipolar gradients of odd
      symmetry designed to cancel such background gradient effects on ADC. The results
      suggest that diffusion-weighted imaging is sensitive to blood-oxygenation and may
      provide a means of measuring changes in blood oxygen. They also provide estimates
      of the potential contribution of susceptibility changes to changes in ADC that
      occur, for example, in stroke and seizure.

PMID- 10080269
TI  - Apparent water diffusion measurements in electrically stimulated neural tissue.
AB  - The effect of stimulation on diffusion characteristics of electrically stimulated
      neural tissue was examined. Bullfrog nerves and spinal cords were excised and
      stimulated electrically during magnetic resonance imaging, and the apparent
      diffusion coefficients (ADCs) of water parallel and perpendicular to the long
      axes of the specimens were mapped with and without stimulation of the tissue.
      Electrophysiological recordings were used to determine the viability of the
      tissue after each experiment. No stimulus-related ADC changes were observed in
      either the peripheral nervous system or the central nervous system tissue. These
      experiments may help to define further the nature of previously reported ADC
      changes in stimulated neural tissue in situ.

PMID- 10080270
TI  - Investigation of the early response to rat forepaw stimulation.
AB  - The role of relative cerebral blood volume (rCBV) in the early response of blood
      oxygenation level-dependent (BOLD) signal following sensory stimulation was
      assessed. Magnetic resonance imaging (MRI) measurements of rCBV and BOLD signal
      as a function of time (t) were compared with relative cerebral blood flow (rCBF)
      obtained by laser doppler flowmetry during a repeated epoch of rat forepaw
      stimulation in which 6 sec of electrical stimulation followed 54 sec of rest.
      rCBF(t) exceeded rCBV(t) in somatosensory cortex at all time points and reached a
      maximal increase (60%) during a 6 sec stimulation that was much higher than
      maximal rCBV (10%). An initial dip was not observed in BOLD signal, which showed
      a delay with respect to rCBF that was roughly consistent with the cerebral blood
      transit time.

PMID- 10080271
TI  - Rotation of NMR images using the 2D chirp-z transform.
AB  - A quick and accurate way to rotate and shift nuclear magnetic resonance (NMR)
      images using the two-dimensional chirp-z transform is presented. When the desired
      image grid is rotated and shifted from the original grid due to patient motion,
      the chirp-z transform can reconstruct NMR images directly onto the ultimate grid
      instead of reconstructing onto the original grid and then applying interpolation
      to get the final real-space image in the conventional way. The rotation angle and
      shift distances are embedded in the parameters of the chirp-z transform. The
      chirp-z transform implements discrete sinc interpolation to get values at grid
      points that are not exactly on the original grid when applying the inverse
      Fourier transform. Therefore, the chirp-z transform is more accurate than methods
      such as linear or bicubic interpolation and is more efficient than direct
      implementation of sinc interpolation because the sinc interpolation is
      implemented at the same time as reconstruction from k-space.

PMID- 10080272
TI  - Classification of human liposarcoma and lipoma using ex vivo proton NMR
      spectroscopy.
AB  - Prognostication in patients with liposarcoma is a complex and controversial
      subject based on recognition of lipoblasts, adipocyte nuclear atypia, and
      qualitative estimations of cellularity and cell size. We show here that for 30
      patients with liposarcoma and 5 patients with lipoma, spectral differences on
      high-resolution, magic angle spinning proton nuclear magnetic resonance (hr-MAS
      1H-NMR) spectroscopy relate to known biochemical changes and correlate with
      adipocyte tissue differentiation, histologic cell type, and cellularity. The NMR
      visible level of triglyceride is shown to correlate with liposarcoma
      differentiation, since the triglyceride level in well-differentiated liposarcoma
      is 33-fold higher on average than for myxoid/round cell liposarcoma, which in
      turn is 6-fold higher than the dedifferentiated and/or pleomorphic subtypes. The
      NMR-visible phosphatidylcholine level serves as an estimate of total tissue cell
      membrane phospholipid mass and was found to correlate with liposarcoma subtype.
      Pleomorphic liposarcoma, the most aggressive and metastatic subtype, was found to
      have a threefold increase in NMR-visible phosphatidylcholine level compared with
      dedifferentiated liposarcoma. The level of NMR-visible phosphatidylcholine was
      twofold greater in well-differentiated liposarcoma compared with lipoma and was
      threefold larger for the hypercellular myxoid/round cell subtype compared with
      the pure myxoid histology. Thus, NMR-derived parameters of tissue lipid may be
      used for objective distinction of liposarcoma histologic subtype/grade and lipoma
      from liposarcoma. These biochemical parameters may ultimately improve
      prognostication in patients with liposarcoma.

PMID- 10080273
TI  - Experimentally verified, theoretical design of dual-tuned, low-pass birdcage
      radiofrequency resonators for magnetic resonance imaging and magnetic resonance
      spectroscopy of human brain at 3.0 Tesla.
AB  - A new theoretical method is presented for designing frequency responses of double
      tuned, low-pass birdcage coils. This method is based on Kirchhoff's equations
      through a nonsymmetric matrix algorithm and extended through a modification of
      the corresponding eigenvalue system from a single-tuned mode. Designs from this
      method are verified for sodium/proton, dual-tuned, double-quadrature, low-pass
      birdcage coils at 1.5 Tesla and 3.0 Tesla and then are used to design dual-tuned,
      double-quadrature, lithium/proton and phosphorus/proton birdcage coils for 3.0
      Tesla. All frequencies show experimental deviations of less than 3% from theory
      under unloaded conditions. The frequency shifts caused by loading and
      radiofrequency shielding are less than 1 MHz and can be compensated readily by
      adjustment of variable capacitors. Applications to human neuroimaging and
      spectroscopy are demonstrated.

PMID- 10080274
TI  - In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and
      choline from large volumes of brain gray and white matter: effects of normal
      aging.
AB  - Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to
      generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All
      subjects also had structural MR scans, and a model, which took into account the
      underlying structural composition of the brain contributing to each metabolite
      voxel, was developed and used to estimate the concentration of the N-acetyl
      moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter.
      NAc concentration (signal intensity per unit volume of brain) was higher in gray
      than white matter and did not differ between young and old subjects despite
      significant gray matter volume deficits in the older subjects. To the extent that
      NAc is an index of neuronal integrity, the available gray matter appears to be
      intact in these older healthy adults. Cr concentrations were much higher in gray
      than white matter and significantly higher in the old than young subjects. Cho
      concentration in gray matter was also significantly higher in old than young
      subjects. Independent determination of metabolite values rather than use of
      ratios is essential for characterizing age-related changes in brain MRS
      metabolites.

PMID- 10080275
TI  - Self-diffusion of water in cartilage and cartilage components as studied by
      pulsed field gradient NMR.
AB  - Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) was used to
      investigate the self-diffusion behavior of water molecules in cartilage,
      polymeric cartilage components, and different model polymers. The short-time self
      diffusion coefficients (diffusion time delta approximately/= 13 msec) are found
      to decrease steadily with decreasing water content. This holds equally well for
      cartilage and cartilage components. The short-time diffusion coefficients are
      subjected to a rather nonspecific obstruction effect and mainly depend on the
      water content of the sample. The long-time diffusion coefficients in cartilage
      (delta approximately/= 500 msec), however, reflect structural properties of this
      tissue. Measurements with varying observation times as well as experiments
      involving enzymatic treatment of articular cartilage suggest that the collagenous
      network in cartilage is likely to be responsible for the observed restricted
      diffusion.

PMID- 10080276
TI  - Mobile lipids in rat brain slices observed by gradient-enhanced NMR.
AB  - Short-echo gradient-enhanced nuclear magnetic resonance (NMR) spectroscopy was
      utilized to identify mobile lipids in perfused neonate and juvenile rat brain
      slices. Lipid signals were present at low levels within 1 hr of tissue
      preparation and increased with time under standard perfusion conditions and in
      the presence of high phosphocreatine and low lactate levels. Both one- and two
      dimensional NMR spectra demonstrate peaks consistent with the generation of free
      fatty acids or neutral lipids following tissue trauma. The present work
      demonstrates that injury-induced mobile lipids may make appreciable contributions
      to regions of brain tissue spectra that have recently been assigned to lactate or
      polypeptides alone.

PMID- 10080277
TI  - Perfusion analysis using dynamic arterial spin labeling (DASL).
AB  - A variety of magnetic resonance (MR) techniques have proved useful to quantify
      perfusion using endogenous water as a blood flow tracer. Assuming that water is a
      freely diffusable tracer, the model used for these techniques predicts that the
      quantitation of perfusion is based on three parameters, all of which can depend
      on blood flow. These are the longitudinal tissue relaxation time, the transit
      time from point of labeling to tissue, and the difference in tissue MR signal
      between an appropriate control and the labeled state. To measure these three
      parameters in parallel, a dynamic arterial spin labeling (DASL) technique is
      introduced based on the analysis of the tissue response to a periodic time
      varying degree of arterial spin labeling, called here the labeling function (LF).
      The LF frequency can be modulated to overdetermine parameters necessary to define
      the system. MR schemes are proposed to measure the tissue response to different
      LF frequencies efficiently. Sprague-Dawley rats were studied by DASL, using
      various frequencies for the LF and various arterial pCO2 levels. During data
      processing, the periodic behavior of the tissue response to the LF allowed for
      frequency filtering of periodic changes in signal intensity unrelated to
      perfusion and arterial spin labeling. Measures of transit time, tissue
      longitudinal relaxation time, and perfusion agreed well over a range of LF
      frequencies and with previous results. DASL shows potential for more accurately
      quantifying perfusion as well as measuring transit times associated with arterial
      spin labeling techniques.

PMID- 10080278
TI  - Flow effects in localized quadratic, partial Fourier MRA.
AB  - A pulse sequence for inflow-enhanced magnetic resonance angiography, including
      localized quadratic encoding, partial-Fourier slice selection, and spiral in
      plane encoding, is analyzed. The through-plane encoding method is discussed in a
      space-spatial frequency context to illustrate some of its properties. This pulse
      sequence has the advantages of being faster and more robust to turbulent flow
      than conventional inflow-enhanced methods. Simulations show the effect of
      different parameters on the modulation-transfer function of the resulting images.
      A flow phantom is used to verify some of the simulation results.

PMID- 10080279
TI  - Does loss of gray- and white-matter contrast in injured spinal cord signify
      secondary injury? In vivo longitudinal MRI studies.
AB  - Longitudinal in vivo magnetic resonance imaging (MRI) of moderately injured rat
      spinal cord was performed to investigate the transient loss in gray matter (GM)
      and white matter (WM) contrast. In addition, neurobehavioral scores (based on
      open field walking, inclined plane test, and grid walking) and tissue cholesterol
      concentrations at pre-determined time points were measured. On MRI, a loss in
      contrast between GM and WM in sections 2-4 mm caudal to the site of injury was
      consistently observed 2 days after injury. A substantial recovery in the contrast
      was observed within 1 week after injury. A strong correlation between the loss of
      GM-WM contrast and the cholesterol concentration was also observed. The
      neurobehavioral scores improved with the return of the GM-WM contrast. These
      serial MRI studies indicate that the loss of contrast in the cord is mainly due
      to edema accumulated in the WM. The resolution of edema seems to occur around the
      same time as the restoration of cholesterol in the cord tissue. It is speculated
      that the compromised membrane stability due to the loss of cholesterol may be one
      of the factors leading to the accumulation of edema in WM.

PMID- 10080280
TI  - Quantifying tissue damage due to focused ultrasound heating observed by MRI.
AB  - Focused ultrasound heating of ex vivo bovine kidney and liver was monitored using
      magnetic resonance imaging (MRI) to investigate the quantitative relationship
      between time-dependent temperature elevations and altered contrast in MR images
      due to thermal coagulation. Proton resonance frequency shift MR thermometry was
      performed during heating at 10 sec intervals (single-slice fast spoiled GRASS
      [FSPGR], theta/TE/TR 30 degrees/11/39 msec, field of view 8 cm, 256 x 256, 3 mm
      slice thickness, 1 NEX); post-heating MR images were T1-weighted (3D-FSPGR,
      theta/TE/TR 60 degrees/25/200 msec, 1 mm slice thickness, 3 NEX). Analysis of the
      resulting temperature versus time data using the Arrhenius relationship and a
      simple binary discrimination model showed that thermal coagulation occurred with
      heating at approximately 54 degrees C for 10 sec in both tissues and could be
      predicted with approximately 625 microm spatial resolution. These results suggest
      that quantitative MR guidance of thermal coagulation therapy is feasible, and
      they provide information useful for designing future investigations in vivo.

PMID- 10080281
TI  - In vivo macrophage activity imaging in the central nervous system detected by
      magnetic resonance.
AB  - Cell-specific imaging has been proposed to increase the potential of magnetic
      resonance imaging (MRI) for tissue analysis. The hypothezis of the present work
      was that following intravenous injection of ultra-small particle iron oxide, a
      contrast agent that accumulates in mononuclear phagocyte cells, macrophages with
      iron burden would be detectable by MRI within the central nervous system at sites
      of inflammatory cellular activity. In experimental autoimmune encephalomyelitis
      in Lewis rats (in which intense macrophage activity results from both
      hematogenous macrophages and activated microglia), lesions have been seen by MRI
      as low signal intensities related to magnetic susceptibility effects induced by
      iron particles. Electron microscopy has revealed the presence of such particles
      within the cytoplasm of cells that had the morphological aspect of macrophages.
      Macrophage activity imaging might increase MRI capability with regard to the in
      vivo pathophysiological aspects of central nervous system (CNS) diseases and
      might help in therapeutic trials in the numerous CNS diseases in which
      macrophages are involved.

PMID- 10080282
TI  - Effects of water exchange on the measurement of myocardial perfusion using
      paramagnetic contrast agents.
AB  - To investigate the effects of water exchange on quantification of perfusion, data
      were acquired in isolated hearts (n = 11) and used to develop a model of
      exchange. Myocardial T1 was measured 3 times/sec during step changes in
      concentration of intravascular (polylysine-gadolinium-diethylene-triamine
      pentaacetic acid) and extracellular (gadoteridol) agents. For the intravascular
      agent, the change in 1/T1 (deltaR1) was lower than predicted by fast exchange
      (2.7+/-0.5 vs. 7.8 sec(-1), respectively), and suggested an intra-extravascular
      exchange rate of 3 Hz. For the extracellular agent, contrast kinetics were
      similar to those of similarly sized molecules (wash-in time constant 38+/-5 sec),
      and the data suggested fast interstitial-cellular exchange. Modeling showed that
      perfusion is underestimated for both agents if exchange is ignored, although the
      relationships of measured to actual perfusion were monotonic. We conclude that
      myocardial water exchange strongly affects first-pass enhancement but that
      ignoring the effects of exchange may still provide reasonable estimates of
      regional perfusion differences.

PMID- 10080283
TI  - Maximum likelihood estimation of cerebral blood flow in dynamic susceptibility
      contrast MRI.
AB  - For quantification of cerebral blood flow (CBF) using dynamic susceptibility
      contrast magnetic resonance imaging (DSC-MRI), knowledge of the tissue response
      function is necessary. To obtain this, the tissue contrast passage measurement
      must be corrected for the arterial input. This study proposes an iterative
      maximum likelihood expectation maximization (ML-EM) algorithm for this
      correction, which takes into account the noise in T2- or T2*-weighted image
      sequences. The ML-EM algorithm does not assume a priori knowledge of the shape of
      the response function; it automatically corrects for arrival time offsets and
      inherently yields positive response values. The results on synthetic image
      sequences are presented, for which the recovered flow values and the response
      functions are in good agreement with their expectation values. The method is
      illustrated by calculating the gray and white matter flow in a clinical example.

PMID- 10080284
TI  - Quantitative tissue sodium concentration mapping of the growth of focal cerebral
      tumors with sodium magnetic resonance imaging.
AB  - Tissue sodium concentration (TSC), as determined by in vivo 23Na magnetic
      resonance imaging (MRI) and the ex vivo classical 22Na radionuclide dilution
      assay (RDA), has been compared in a rat model of a focal glioma. The 23Na MRI
      method used a three-dimensional, twisted projection acquisition scheme at short
      echo time to minimize signal losses from relaxation of transverse magnetization.
      Calibration standards within the field of view allowed quantification of the
      sodium signal in terms of a TSC after correction for B1 nonuniformity and tissue
      water concentration. The 23Na MRI method measured focally increased TSC values in
      tumors that were equivalent statistically to the destructive 22Na RDA method. The
      noninvasive 23Na MRI method provided a quantitative means with which to monitor
      focal brain tumor growth.

PMID- 10080285
TI  - Blood pool agent strongly improves 3D magnetic resonance coronary angiography
      using an inversion pre-pulse.
AB  - The ability of a blood pool contrast agent to enhance MR coronary angiography was
      defined. The proximal coronary vessels of pigs were imaged before and after
      administration of Gd-DTPA bound covalently to bovine serum albumin (0.2 mmol/
      kg). The contrast agent resulted in a reduction of the blood T1 value to 33+/-5
      msec, as determined in vivo with a Look-Locker technique. Both 2D and 3D imaging
      techniques were performed. An inversion pulse suppressed the signal of nonblood
      tissue postcontrast. After contrast agent administration, in the 3D data set the
      signal-to-noise ratio (SNR) of blood and contrast-to-noise ratio (CNR) of blood
      to myocardium were improved by factors of 2.0+/-0.2 and 15+/-8, respectively (P <
      0.05). Postcontrast, the 3D acquisition was superior to the 2D technique in terms
      of spatial resolution, SNR of blood, and CNR of blood to myocardium. The high
      contrast of the 3D data set allowed for direct and rapid display of coronary
      arteries using a "closest vessel projection."

PMID- 10080286
TI  - Rapid T2* mapping using interleaved echo planar imaging.
AB  - Magnetic resonance imaging methods that are sensitive to T2* are widely used in
      the study of blood oxygenation changes, most notably in functional studies of the
      brain. In these studies the signal intensity change in T2*-weighted imaging is
      related to the coupling of cerebral blood flow and metabolism. Rapid measurement
      of T2* itself would offer a valuable method to quantify blood oxygenation changes
      indirectly and monitor their time course. An interleaved echoplanar imaging (EPI)
      sequence is presented here that allows maps of T2* to be generated in a few
      seconds. The sequence benefits from reduced geometric distortion and an improved
      point spread function compared with single-shot EPI. A comparison among a set of
      T2*-weighted interleaved EPI images, single-shot EPI, and conventional gradient
      echo and spin-echo methods is made using a compartmentalized doped water phantom.
      The interleaved sequence yields accurate T2* values when compared with reference
      measurements made using the slower gradient-echo technique. Data acquired from
      the rat brain at 2.35 T prior to and during an anoxic challenge show, with high
      temporal resolution, the reduction in T2* associated with increased levels of
      deoxyhemoglobin.

PMID- 10080287
TI  - Multi-echo segmented k-space imaging: an optimized hybrid sequence for ultrafast
      cardiac imaging.
AB  - Cardiac magnetic resonance imaging requires high temporal resolution to resolve
      motion and contrast uptake with low total scan times to avoid breathing
      artifacts. While spoiled gradient echo (SPGR) imaging is robust and reproducible,
      it is relatively inefficient and requires long breath-holds to acquire high time
      resolution movies of the heart. Echo planar imaging (EPI) is highly efficient
      with excellent signal-to-noise ratio (SNR) behavior; however, it is particularly
      difficult to use in the heart because of its sensitivity to chemical shift,
      susceptibility, and motion. EPI may also require reference scans, which are used
      to measure hardware delays and phase offsets that cause ghosting artifacts; these
      reference scans are more difficult and less reliable in the heart. Consequently,
      a hybrid EPI/SPGR sequence is proposed for application to rapid cardiac imaging.
      A detailed optimization of SNR and echo train length for multi-echo sequences is
      presented. It is shown that significant reductions in total scan time are
      possible while maintaining good image quality. This will allow complete motion
      sampling of the entire heart in one to three breath-holds, necessary for MR
      cardiac dobutamine stress testing. Improved speed performance also permits
      sampling of three to six slices every heartbeat for bolus injection perfusion
      studies.

PMID- 10080288
TI  - T1 imaging using phase acquisition of composite echoes.
AB  - A new magnetic resonance method for T1 imaging is presented. It is based on the
      simultaneous acquisition of a spin echo and a phase-shifted, stimulated echo. The
      phase of this composite echo image is modulated heavily by the spin-lattice
      relaxation time T1, whereas spin density and T2 do not influence the phase
      information. This phase information can be assigned easily to corresponding T1
      values. Although this method is sensitive to radiofrequency inhomogenities,
      phantom studies showed that high precision and reasonable accuracy of T1
      determination can be achieved. Moreover, this method was found to be very robust,
      because no fitting is required. T1 imaging of the human brain was performed to
      confirm the in vivo utility of this method.

PMID- 10080289
TI  - Coronary artery imaging in a 0.5-Tesla scanner: implementation of real-time,
      navigator echo-controlled segmented k-space FLASH and interleaved-spiral
      sequences.
AB  - Coronary angiography techniques have been implemented on a 0.5-Tesla scanner with
      a view to performing coronary artery imaging. Slice-followed, segmented k-space
      FLASH sequences and interleaved-spiral sequences have been employed with
      acquisitions under real-time navigator echo control with patient feed back,
      enabling poor signal-to-noise levels to be overcome by averaging data acquired
      over multiple, variable-length, reproducible breath holds. Good-quality,
      millimetre-resolution coronary images were obtained in ten normal subjects with
      both techniques. The mean percent of data segments or interleaves acquired with
      the navigator echo within the 5-mm diaphragm acceptance window was 57% [standard
      deviation (S.D.), 11%; range, 38-85%], and the average image-acquisition times
      were 123+/-22 sec and 71+/-14 sec for segmented FLASH and interleaved-spiral
      imaging, respectively. In addition to shorter acquisition times, the interleaved
      spiral sequence has superior temporal resolution, allowing the acquisition of
      limited, multislice data sets. However, the sequence is particularly sensitive to
      the off-resonance effects of residual epicardial fat surrounding the artery and
      to field nonuniformities, both of which lead to image blurring and, unlike
      segmented FLASH acquisitions (which are very robust), the spiral data sets
      generally require postprocessing.

PMID- 10080290
TI  - Magnesium and pH imaging of the human brain at 3.0 Tesla.
AB  - Multislice, two-dimensional phosphorus 31 spectroscopic imaging (SI) of human
      brain was performed in 15 normal volunteers on a 3-Tesla magnetic resonance
      system. Images of free magnesium concentrations and pH as well as phosphoesters,
      inorganic phosphate, phosphocreatine, and adenosine triphosphate (ATP), were
      calculated from the SI data. By using the equations of Golding and Golding (Magn.
      Reson. Med. 1995;33: 467-474), average [Mg2+] for all brain regions studied was
      0.42+/-0.05 mM, whereas average brain pH was found to be 7.07+/-0.03, with no
      significant regional variations. Phosphorus metabolite concentrations (relative
      to ATP, assumed to be 3.0 mM/kg wet weight)were 5.39+/-1.88, 1.30+/-0.39, 5.97+/
      3.17, and 4.33+/-1.45 mM/kg wet weight for phosphomonoesters, inorganic
      phosphate, phosphodiesters, and phosphocreatine (PCr), respectively. These values
      are in good general agreement with those reported previously. Typical signal-to
      noise ratios of 15:1 were obtained for PCr in spectra from nominal 31.5 cc voxel
      sizes with a 34-min scan time. Limits on spatial resolution and the likely error
      of the magnesium and pH values are discussed.

PMID- 10080291
TI  - Quantification of dynamic changes in cerebral venous oxygenation with MR phase
      imaging at 1.9 T.
AB  - A double-echo magnetic resonance (MR) phase imaging method was used to measure
      the time-dependent changes in regional cerebral venous blood oxygenation during
      neural stimulation. Our results showed that a finger opposition task induced an
      absolute increase of blood oxygenation level of deltaY = 0.16+/-0.05 (n = 6),
      which was measured in the small veins located in the left central sulcus. It was
      observed that there is a long temporal delay of approximately 27 sec after the
      onset of the task to reach the steady-state venous oxygenation. This work
      demonstrated that MRI is a powerful clinical tool for in vivo monitoring of the
      dynamic nature of organ-specific venous blood oxygenation.

PMID- 10080292
TI  - Comparison of evoked cortical activity in conscious and propofol-anesthetized
      rats using functional MRI.
AB  - Changes in cortical activity during foot shock were assessed under conscious and
      propofol-anesthetized conditions using functional magnetic resonance imaging
      (fMRI). Increases in signal intensity were observed in the contralateral
      somatosensory cortex in response to electrical shock of the hindpaw under both
      conditions. These increases in cortical signal ranged from 6% to 26% while awake
      and from 1% to 6% under propofol anesthesia. In each of the six animals studied,
      the largest increase in blood oxygenation level-dependent (BOLD)-based signal
      intensity was observed during consciousness. In three of six animals, propofol
      anesthesia depressed signal intensity by as much as 10-fold, showing that the
      level of cortical activity during foot shock is dampened by anesthesia. These
      results indicate it would be advantageous to use fully conscious animals to
      maximize BOLD-based MRI signal in certain behavioral studies using MR
      spectrometers with modest field strengths (1.0-2.0 T).

PMID- 10080293
TI  - Effects of interleaf order for spiral MRI of dynamic processes.
AB  - The effects of the temporal order in which spiral interleaves are collected are
      discussed, in the context of artifacts from moving or changing objects.
      Simulations and in vivo experiments demonstrate the properties of four different
      ordering methods. Specific applications discussed include cardiac and
      interventional magnetic resonance imaging, as well as inflow and contrast
      enhanced magnetic resonance angiography.

PMID- 10080294
TI  - Multiple echo frequency-domain image contrast: improved signal-to-noise ratio and
      T2 (T2*) weighting.
AB  - Conventional T2- and T2*-weighted image contrasts are produced by waiting a TE
      period for the transverse magnetic resonance (MR) signals to decay to
      differentiate tissue types with distinct relaxation rates. Significant image
      signal-to-noise ratio (SNR) is compromised by this contrast-producing process. In
      this report, a multiple echo frequency-domain image contrast (MEFIC) method is
      presented. During the conventional TE period, a multiple echo train modulated by
      T2 or T2* decay is acquired. A third Fourier transform along the echo direction
      produces an image set with pixel signal intensity modulated by the spectrum of
      the decay curve. This method simultaneously enhances image contrast with a large
      increase in SNR. Experimental studies of cerebral vasogenic edema in immature
      rats and functional MR imaging studies of the human motor cortex have
      demonstrated that the MEFIC method produces superior image quality over
      conventional methods for generating T2- and T2* weighted images.

PMID- 10080295
TI  - The legislation of toxicologic safety factors: the Food Quality Protection Act
      with chlorpyrifos as a test case.

PMID- 10080296
TI  - Teratogenic effects of the endothelin receptor antagonist L-753,037 in the rat.
AB  - The studies presented in this paper were undertaken to investigate the effects of
      L-753,037, a balanced endothelin receptor antagonist with similar affinity for
      the ET(A) and ET(B) receptors (Ki = 0.03 to 0.12 nM and 0.1 to 3.33 nM,
      respectively), when administered to pregnant female rats by oral gavage, on the
      development, growth, maturation, and reproductive performance of the F1
      generation. Following embryonic exposure to L-753,037, profound craniofacial,
      cardiovascular, and viscerocranial malformations were noted in the F1 generation.
      All of the affected organs are derived, in part, from cranial neural crest cells
      predominantly originating from the posterior midbrain through the hindbrain and
      destined for the pharyngeal arches. In contrast, cranial structures derived from
      the paraxial mesoderm (i.e., basisphenoid) were of normal shape and size. There
      were no apparent effects on enteric neural crest cell derivatives. Based on the
      phenotype of affected fetuses and their similarity to fetuses with gene knockouts
      of ET-1 or the ET(A) receptor, the observed alterations are considered to be a
      pharmacologically mediated class effect on cranial neural crest cells. The
      phenotype observed suggests that ET(A) receptor antagonism may have specific
      effects on cranial neural crest cell migration and/or proliferation.

PMID- 10080297
TI  - Heat shock during rat embryo development in vitro results in decreased mitosis
      and abundant cell death.
AB  - Epidemiologic studies strongly suggest that in utero exposure to hyperthermia
      results in developmental defects in humans. Rats, mice, guinea pigs, and other
      species exposed to hyperthermia also exhibit a variety of developmental defects.
      Studies in our laboratory have focused on exposure to hyperthermia on Gestation
      Day (GD) 10 of rats in vivo or in vitro. Within 24 h after in vivo or in vitro
      exposure, delayed or abnormal CNS, optic cup, somite, and limb development can be
      observed. At birth, only rib and vertebral malformations are seen after
      hyperthermia on GD 10, and these have been shown to be due to alterations in
      somite segmentation. Unsegmented somites have been thought to result from a cell
      cycle block in the presomitic mesoderm, from which somites emerge individually
      during normal development. In the present study, DNA fragmentation (terminal
      deoxynucleotidyl transferase (TdT) catalyzed fluorescein-12-dUTP DNA end
      labelling), indicative of apoptotic cell death, and changes in cell proliferation
      were examined in vitro in 37 degrees C control and heat treated (42 degrees C for
      15 min) GD 10 CD rat embryos. Embryos were returned to 37 degrees C culture
      following exposure and evaluated 5, 8, or 18 h later. A temperature-related
      increase in TdT labelled cells was observed in the CNS, optic vesicle, neural
      tube, and somites. Increased cell death in the presomitic mesoderm also was
      evident. Changes in cell proliferation were examined using the cell-specific
      abundance of proliferating cell nuclear antigen (PCNA) and the quantification of
      mitotic figures. In neuroectodermal cells in the region of the optic cup, a
      change in the abundance of PCNA was not apparent, but a marked decrease in
      mitotic figures was observed. A significant change in cell proliferation in
      somites was not detected by either method. These results suggest that acute
      hyperthermia disrupts embryonic development through a combination of
      inappropriate cell death and/or altered cell proliferation in discrete regions of
      the developing rat embryo. Furthermore, postnatal vertebral and rib defects
      following disrupted somite development may be due, in part, to abundant cell
      death occurring in the presomitic mesoderm.

PMID- 10080298
TI  - Variability of lipid hydroperoxides in pregnant and nonpregnant women.
AB  - Lipid peroxidation is thought to be important in numerous disease states,
      including pregnancy complications. Study of its role requires markers, but the
      variability of available markers in non-diseased populations has not been well
      characterized. We examined the variability over time of blood lipid
      hydroperoxides, as measured by iodometric analysis, in 49 healthy young women, 21
      nonpregnant and 28 pregnant. Lipid hydroperoxides from the same woman were very
      similar from one day to the next but were less stable over periods of a month or
      more. The correlation between measurements on consecutive days was 0.98; the
      correlation between measurements a month or more apart was 0.11. Variability over
      time was not attributable to seasonal effects or, among the pregnant women, to
      differences over the course of pregnancy. Knowledge of the variability of this
      and other markers of oxidative damage enables the development of appropriate
      study designs.

PMID- 10080299
TI  - Isotretinoin alters morphology, polarity, and motility of neural crest cells in
      culture.
AB  - Migrating neural crest cells (NCCs) contribute to a diverse array of vertebrate
      head and neck structures. Retinoids are proven human and animal teratogens. To
      elucidate isotretinoin's effects, cranial and trunk neural folds were
      microdissected from chick embryos and cultured. Image analysis and immunostaining
      were used to quantitate cell behavior. We found that a higher proportion of Stage
      8, 9, and 10 treated NCCs were rounded and clustered. Medians and means for cell
      area, perimeter, and elongation index were lower for treated cells from Stage 9
      and 10 embryos, but not from Stage 8. Cumulative medians and means for changes in
      area and perimeter, and cell migration were similarly lower. Thus interference
      with the transitory basal activity of the cytoskeleton that adjusts and
      determines cell-substratum adhesion, spreading, elongation, and migration may be
      the mechanism by which isotretinoin acts on NCCs in slightly older embryos.

PMID- 10080300
TI  - Maternal trace elements, vitamin B12, vitamin A, folic acid, and fetal
      malformations.
AB  - The demonstrated teratogenicity of maternal zinc deficiency in rats has led to
      burgeoning interest in zinc and other trace elements as important factors in
      embryonic development. Levels of zinc, copper, manganese, magnesium, folic acid,
      vitamin B12 and vitamin A were evaluated at the beginning of pregnancy in the
      plasma of pregnant women who later delivered a malformed newborn. Fetal
      chromosomal anomalies and recognizable nonchromosomal syndromes were excluded.
      The results were compared to control women who delivered normal babies. One
      hundred seventy mothers had malformed children. The more frequent congenital
      malformations were congenital heart diseases (72 cases including 24 VSD),
      musculoskeletal malformations (21 cases), urogenital malformations (23 cases),
      spina bifida (6 cases), hydrocephaly (6 cases), and labial cleft (14 cases).
      Maternal plasma concentrations of zinc, copper, magnesium, manganese, folate,
      vitamin B12, and vitamin A of malformed children did not differ from controls.
      Thus vitamin profiles do not form a suitable means for identifying women at risk
      for having a child with congenital malformations.

PMID- 10080301
TI  - Reversible contraception with chloroform extract of Carica papaya Linn. seeds in
      male rabbits.
AB  - The contraceptive efficacy and reversibility of the chloroform extract of the
      seeds of Carica papaya in adult male rabbits were investigated. Eighteen adult
      male rabbits were divided into three groups of six animals each; Group I-
      control, Group II--administered chloroform extract of the seeds of Carica papaya
      at 20 mg/animal/d for 150 d by gavage, and Group III--administered the seed
      extract at 50 mg/animal/d for 150 d. Body weight and organ weight, semen
      analysis, sperm morphology by scanning electron microscopy, semen biochemistry,
      histology of the testis, haematology, serum clinical biochemistry, and the
      fertility status of the control and the treated animals were evaluated. Body
      weight and the weight of the testis, epididymis, seminal vesicles, and prostate
      did not show appreciable changes. Sperm concentration showed a gradual decline,
      reached severe oligospermia (fewer than 20 million/mL) after 75 d treatment, and
      attained uniform azoospermia after 120 d treatment. Sperm motility and viability
      were severely affected after 45 d treatment and reached less than 1% after 75 d
      treatment. The morphology of the spermatozoa by scanning electron microscopy
      revealed membrane damage in the acrosome, bent midpiece, coiled tail, and
      detached head and tail. The levels of fructose, glycerylphosphorylcholine, acid
      phosphatase, and lactate dehydrogenase in the seminal plasma were unaltered.
      Histology of the testis revealed arrest of spermatogenesis beyond the level of
      spermatocytes. No toxicity was evident from the haematology and serum
      biochemistry parameters. The libido of the treated animals was unaffected and the
      fertility rate was zero. The effects were comparable in both the dose regimens
      (Groups II and III) and were restored to normal 45 d after withdrawal of the
      treatment.

PMID- 10080302
TI  - Early effects of ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats and
      mice.
AB  - The industrial chemical 4-vinylcyclohexene diepoxide (VCD) causes specific
      destruction of oocyte-containing small preantral follicles (primordial and
      primary) in ovaries of rats and mice. The mouse seems more susceptible to
      ovotoxic effects of VCD than the rat. The purpose of this study was to better
      understand these species differences in susceptibility to VCD by comparing the
      initial rates of VCD-induced follicle damage and loss in response to dosing in
      both species. Female Fischer 344 rats and B6C3F1 mice (age, Day 28) were dosed
      daily (vehicle or 80 mg/kg, i.p.) for 6, 8, 10, or 12 d. Ovaries collected after
      the final dose were prepared for histologic evaluation. Primordial and primary
      follicles in ovarian slices were counted and classified as healthy or atretic. A
      VCD-dependent increase (P < 0.05) in percent atretic primordial follicles was
      first observed 4 h after the final dose in mice on Day 8 (VCD-treated, 44.4 +/-
      3.1% vs. control, 26.9 +/- 5.4%). Conversely, in rats, this significant increase
      was not seen until Day 10 (VCD-treated, 44.3 +/- 1.3% vs. control, 23.1 +/-
      4.0%). A VCD-dependent increase in percent atretic primary follicles was not
      observed in either species before Day 12. There was no significant effect on
      growing or preantral follicles on any day in either species. Significant loss of
      primordial and primary follicles (P < 0.05) was first measured on day 12 in both
      rats and mice. However, when compared with controls, follicle loss on that day
      was greater (P < 0.05) in mice (64.2 +/- 4.5%) than in rats (34.7 +/- 4.9%). Once
      VCD-dependent follicle loss was observed, the rate of follicle damage was similar
      in rats and mice, and was fairly constant in response to each dose. VCD-induced
      follicle damage in mice, as with rats, also displayed morphologic characteristics
      of atresia (apoptosis). In summary, follicle destruction seems to be similar in
      rats and mice; however, follicle damage is initiated earlier and to a greater
      extent in mice than in rats. Additionally, ovotoxic effects of VCD seem to
      initially directly target primordial follicles. These results provide temporal
      evidence that mice are more susceptible to VCD-induced ovotoxicity than rats.

PMID- 10080303
TI  - Classification terms in developmental toxicology: need for harmonisation. Report
      of the Second Workshop on the Terminology in Developmental Toxicology Berlin, 27
      28 August 1998.

PMID- 10080304
TI  - Six-year follow-up of titanium and high-gold porcelain-fused-to-metal fixed
      partial dentures.
AB  - In a randomized clinical study 47 titanium and gold-alloy fixed partial dentures
      (FPDs) were placed during a 1-year period. In the titanium group (n = 22) all
      metal substructures were made of unalloyed titanium. The titanium substructures
      were fabricated by copy milling, spark erosion and laser welding (Procera,
      Nobelpharma). Ceramic veneering was carried out with Duceratin titanium ceramics
      (Ducera, Germany). In the control group (n = 25) the high-gold alloy Degudent U
      (Degussa, Germany) and Vita VMK 68 ceramics (Vita, Germany) were used. The
      longest observation time was 6 years. Only one FPD had to be removed due to metal
      ceramic failure (titanium group). The clinical performance of all 125 porcelain
      fused-to-metal (PFM) veneers with respect to the longevity of the metal-ceramic
      compound was described by Kaplan-Meyer survivor analyses. Relating survival to a
      completely intact ceramic veneer, the 5-year survivor rate was 84% for titanium
      and 98% for the high-gold alloy. PFM titanium restorations exhibited a
      significantly increased risk of metal-ceramic failure. However, concerning
      defects requiring removal, no significant differences in titanium versus high
      gold alloy occurred. There were no significant differences in the survival
      distributions between crowns and pontics within the two groups.

PMID- 10080305
TI  - Techniques for the production of dental eroded lesions in vitro.
AB  - This project firstly demonstrated an in vitro technique for the production of
      eroded lesions which simulates the in vivo conditions, and secondly evaluated the
      influence of salivary parameters on the degree of erosion in vitro. Teeth were
      sectioned sagitally into three equal portions. The portions were randomly
      assigned to one of three experimental groups (A, B and C). Lesions were produced
      by cycling the teeth between orange juice and either artificial saliva (A) or
      water (B) for a total period of 12 h, or by a single 12 h immersion in orange
      juice (C). Sections were prepared from each specimen and mineral loss was
      quantified using transverse microradiography. Mineral loss was significantly
      lower in group A compared with B and C. Greatest mineral loss was observed in B
      though not significant when compared with C. The present technique mimics the in
      vivo conditions with the saliva reducing the degree of erosion and possibly
      remineralizing the lesions.

PMID- 10080306
TI  - Urinary catecholamine levels and bruxism in children.
AB  - This study was performed to test the hypothesis that emotionally stressful states
      measured by the urinary catecholamines may affect the development of bruxism.
      Three hundred and fourteen children, boys and girls, aged 6-8 years were included
      in this study. Bruxism was recorded by a clinical examination and an interview.
      Positive evidence of this parafunction was defined as the presence of both
      historical and clinical indicators. Information concerning systemic and socio
      economic factors was collected by a questionnaire. A 24-h urine sample was
      collected for each subject and analysed by the high performance liquid
      chromatography technique to assay the catecholamine content. Of the total of 273
      children who had a complete 24-h urine sample, 167 were identified to be with and
      without positive evidence of bruxism. The logistic multiple-regression analysis
      was carried out to test whether the presence of bruxism was affected by the
      variables studied; 95% probability was used. The results showed that epinephrine
      and dopamine had a significant and strong association with bruxism. The data
      therefore provide support for the concept that emotional stress is a prominent
      factor in the development of bruxing behaviour.

PMID- 10080307
TI  - Stress distribution and abutment tooth mobility of distal-extension removable
      partial dentures with different retainers: an in vivo study.
AB  - Three types of retainers (wrought wire clasp, Aker's cast clasp, and conical
      crown telescopic retainer) designed for distal-extension removable partial
      dentures (RPDs) were assessed in two Kennedy class I patients' mouths. The
      assessment, included the ratio of denture base shearing load and mobility of the
      terminal abutments when loaded on a free-end RPD occlusal surface. The mean
      values of denture base shearing ratios of wrought wire clasp, Aker's clasp and
      conical crown telescope were 60, 42 and 20%, respectively. The abutment mobility
      of the three types of retainers were all within the 'mobile ability area' except
      the wrought wire clasp for patient A's right side. The greatest tooth mobility
      was observed with the wrought wire clasps, followed by Aker's clasp and the
      conical crown telescopic retainer. From the analysis the following was concluded:
      (i) different retainers do influence the occlusal load distribution; (ii) the
      occlusal load distributed to the free-end saddle is closely related to the
      connecting rigidity of the retainer; (iii) mucosal support has an indispensable
      role in sharing the occlusal load with various retainers, even the rigid
      telescopic retainer.

PMID- 10080308
TI  - Influence of mandibular length on mouth opening.
AB  - Theoretically, mouth opening not only reflects the mobility of the
      temporomandibular joints (TMJs) but also the mandibular length. Clinically, the
      exact relationship between mouth opening, mandibular length, and mobility of TMJs
      is unclear. To study this relationship 91 healthy subjects, 59 women and 32 men
      (mean age 27.2 years, s.d. 7.5 years, range 13-56 years) were recruited from the
      patients of the Department of Oral and Maxillofacial Surgery of University
      Hospital, Groningen. Mouth opening, mobility of TMJs and mandibular length were
      measured. The mobility of TMJs was measured as the angular displacement of the
      mandible relative to the cranium, the angle of mouth opening (AMO). Mouth opening
      (MO) correlated significantly with mandibular length (ML) (r = 0.36) and AMO (r =
      0.66). The regression equation MO = C1 x ML x AMO + C2, in which C = 0.53 and C2
      = 25.2 mm, correlated well (r = 0.79) with mouth opening. It is concluded that
      mouth opening reflects both mobility of the TMJs and mandibular length.

PMID- 10080309
TI  - Fluoride release from aesthetic dental materials.
AB  - The objective of the study was to compare the amounts of fluoride released by two
      glass-ionomer cements, a resin-modified glass-ionomer cement, a compomer and a
      fluoride-containing composite into deionized water and artificial saliva. Disc
      samples of each of the materials were fabricated and placed in either water or
      artificial saliva. Fluoride analysis of the media was performed periodically over
      64 days. The data were analysed to show the rate of fluoride release per cm2 per
      hour for each material. The results showed that the fluoride release rate for all
      the materials in both solutions decreased dramatically after 24 h. The release
      rate in artificial saliva was significantly less than in water (P < 0.001). The
      resin-modified glass-ionomer cement consistently displayed the highest fluoride
      release rate per hour into both media.

PMID- 10080310
TI  - In vitro study of the effect of thermo- and load-cycling on the bond strength of
      porcelain repair systems.
AB  - Fracture of porcelain fused to metal veneering may cause premature failure of
      fixed partial prosthodontics. Through the use of intra-oral composite bonded
      porcelain repair systems, the replacement of the prosthetic reconstruction can be
      avoided. The aim of this study was to evaluate the shear bond strength of
      porcelain repair systems currently in use and the effect of thermocycling and
      mechanical loading (TCML) on the adhesion of composite to ceramic surfaces in
      comparison with the composite to metal bonding system Rocatec. Specimens were
      fabricated by fusing the veneering ceramic VMK-68 (Vita) to Co-Cr-Mo-alloy base
      plates. Twenty cylindrically shaped composite samples in each series were bonded
      to the porcelain surface using porcelain repair systems currently in use. The
      shear bond strength of 10 samples was evaluated after 24 h (baseline) and after
      loading in an artificial oral environment. The repair systems Z 100 Kit, Monobond
      S/Tetric and Porcelain Etch were not impaired by TCML and exhibited a shear bond
      strength of greater than 12 MPa, which was comparable to the control group
      Rocatec. The shear strength of the repair systems Silistor and All-Bond 2
      decreased significantly after TCML. Using the appropriate repair system, the
      repair of ceramic-veneered fixed partial prosthodontics can be recommended as a
      medium term alternative to a new reconstruction.

PMID- 10080311
TI  - Bilateral variation of the masseteric myotatic reflex and the silent period in
      young humans.
AB  - Increased bilateral differences in jaw reflexes have been considered as
      pathological findings. The aim of this study was to investigate the normal
      variation between sides in the jaw jerk and the silent period and determine the
      range of its boundaries, using the present experimental set-up. Electromyographic
      data were simultaneously recorded from the right and left masseter muscles by
      surface electrodes, using a computerized recording and analysis system. The
      reflexes were elicited by chin taps during mandibular rest and at moderate
      intercuspal clenching in 20 healthy dentate adults (10 males and 10 females) with
      a mean age of 26 years. The reflexes were always elicited bilaterally and no
      overall significant differences were observed between sides for occurrence,
      latency, duration and amplitude of the jaw jerk and for the latency and duration
      of the silent period (P > 0.05). However, in the individual analysis significant
      bilateral variation was occasionally recorded, particularly for the jaw jerk at
      rest and mainly in the amplitude measurements. On the other hand, in the silent
      period duration measurements individual variation was very limited. Bilateral
      individual latency differences for the jaw jerk did not exceed 1 ms at rest (x =
      0.3 +/- 0.3 ms) and 0.7 ms at clench (x = 0.3 +/- 0.2 ms), while latency
      differences for the silent period did not exceed 0.8 ms for the early type (x =
      0.4 +/- 0.2 ms) and 4.8 ms for the late phase of depression (x= 1.9 +/- 1.7 ms).
      Bilateral differences for the silent period duration did not exceed 7.1 ms (x =
      2.2 +/- 2.3 ms) in the early type (simple + early phase of combined types) and
      3.3 ms (x = 1.5 +/- 0.9 ms) in the total duration of the combined types.

PMID- 10080312
TI  - Amplitude and frequency spectrum of temporomandibular joint sounds from subjects
      with and without other signs/symptoms of temporomandibular disorders.
AB  - Temporomandibular joint (TMJ) sound is one of the most commonly recognized signs
      in patients with temporomandibular disorders (TMD) but is also frequently seen in
      asymptomatic individuals. Sound recording is therefore only meaningful if the
      sounds from a normal healthy joint can be differentiated from those in patients.
      In this study, the amplitude and power spectrum of the TMJ sounds from
      symptomatic patients and asymptomatic individuals were recorded and compared. The
      result showed that TMJ sounds from symptomatic patients had a larger amplitude
      than sounds from asymptomatic subjects. A significant proportion of sounds had
      frequencies between 2000 and 3000 Hz. It was concluded that the characteristic
      amplitude is worthy of further study as a sign of possible diagnostic value.
      Secondly, the bandwidth of the sensors used at electronic TMJ sound recording
      should not be less than 3000 Hz.

PMID- 10080313
TI  - Antibacterial synergistic effect of chlorhexidine and hydrogen peroxide against
      Streptococcus sobrinus, Streptococcus faecalis and Staphylococcus aureus.
AB  - Chlorhexidine (CHX) and Hydrogen peroxide (HP) are potent antibacterial agents
      that are used in controlling dental plaque. However, both agents bear undesired
      side-effects. We have tested the hypothesis that an antibacterial synergistic
      effect can occur between the two agents against Streptococcus sobrinus,
      Streptococcus faecalis and Staphylococcus aureus. We have found that at several
      combinations of HP and CHX an antibacterial synergistic effect does occur, while
      at other combinations a on-significant synergism was noticed. No antagonism
      between the two agents was found in our experimental system. It can be postulated
      that the mechanism of this synergistic effect is via alteration of the bacterial
      cell-surface by CHX thereby allowing for an increased amount of HP to penetrate
      and to react with the intercellular organelles of the bacteria. These results
      suggest that CHX and HP can be of use in controlling the dental plaque in the
      oral cavity.

PMID- 10080314
TI  - Analysis of a restored maxillary second premolar tooth by using three-dimensional
      finite element method.
AB  - In the first part of this study some physical properties of restorative
      materials, amalgam, glass-ionomer and composite resin were measured
      experimentally. In the second part a numerical study was carried out, for which
      the maxillary second premolar tooth was used. The tooth model was restored with
      composite resin and amalgam on glass-ionomer, which was used as the base
      material. The stress distribution investigated was the resultant of the stresses
      which come from the mastication force and those resulting from the contraction
      and expansion of restorative materials. All calculations were carried out using
      the finite element method and programs were written using FORTRAN 77. A load of
      450 N, at an angle of 45 degrees to the longitudinal axis was applied on the
      occlusal margin of the tooth. The tooth was assumed isotropic, homogenous,
      elastic and unsymmetrical. The distribution of compressive, tensile and shear
      stresses were plotted for the whole tooth structure.

PMID- 10080315
TI  - Further aspects of design for distal extension removable partial dentures based
      on the Kennedy classification.
AB  - A supplement to the Kennedy classification of partially edentulous arches for
      restoration with removable partial dentures has been suggested. Factors affecting
      denture design relating to the position of the abutment teeth, the symmetry of
      the edentulous distal extensions, the arch form and the cross-sectional shape of
      the residual ridges have been discussed and classified. An understanding of the
      movement of the denture bases in relation to the influence of these factors makes
      for a rational approach to removable partial denture design and the treatment of
      complications observed clinically in removable partial denture wearers.

PMID- 10080316
TI  - In vitro corrosion behaviour and microhardness of high-copper amalgams with
      platinum and indium.
AB  - Samples prepared from Luxalloy, GS-80, Permite-C and Logic and polished after 24
      h by traditional methods were stored in polypropylene tubes containing phosphate
      buffered saline solutions (pH 3.5 and 6.5) and distilled water. The amounts of
      mercury, silver, tin, copper, zinc, platinum and indium in the test solutions
      were determined at the first, second, eighth, 52nd and 78th week by atomic
      absorption spectrometry. At the end of the eighth week the amalgam samples were
      removed from solutions and evaluated by Rockwell Super Scial Microhardness
      tester. Statistically significant low amounts of metal ions were measured for
      Permite-C containing indium and Logic containing platinum. The microhardness test
      results showed that there were statistically significant increases in the
      microhardness of Permite-C and Logic. As a result it was shown that the amalgam
      samples were affected from corrosion conditions to different degrees. Sample of
      the Logic group that was stored in distilled water, showed smoother surface
      properties than other amalgam samples containing high copper. However, it was
      observed that samples of Permite-C group had the smoothest surface properties.

PMID- 10080317
TI  - Examining the secretor status in the saliva of patients with oral pre-cancerous
      lesions.
AB  - It has been demonstrated in a number of earlier studies on the aetiology and
      pathogenesis of certain diseases that the patients' secretor status (ABO (H)
      blood group antigens) may possibly be a factor influencing the development of
      systemic oral diseases. This likelihood has prompted the present study, to
      examine the differences in the saliva secretor status by comparing patients with
      oral pre-cancerous lesions on the one hand, and the healthy population on the
      other; (i) in relation to the intensity of the clinical manifestation of diseases
      and (ii) in relation to the intensity of epithelial dysplasia of patients with
      oral pre-cancerous lesions. In total 122 subjects were examined, half of whom
      suffered from oral pre-cancerous lesions (excluding Candida albicans in oral
      smears), while the other half were the healthy control group. All were subjected
      to clinical oral examinations and standard evaluation tests in order to establish
      the secretor status of their saliva. In the group of patients with oral pre
      cancerous lesions (experimental group), a pathohistological examination of the
      oral mucosa was performed. The results have demonstrated that the large majority
      of the people examined in both groups were secretors and no significant
      difference between secretors and non-secretors was found in the comparison
      between the experimental group and the healthy control group. However, (i) we
      found a higher intensity of oral disease in the non-secretor group, and (ii) the
      occurrence of epithelial dysplasia was found exclusively in the non-secretor
      group.

PMID- 10080318
TI  - Finishing and polishing of the ceromer material Targis. Lab-side and chair-side
      methods.
AB  - The aim of the study was to check four lab-side and four chair-side methods for
      finishing and polishing the ceromer material Targis. Eighty bar-shaped specimens
      (20 mm x 10 mm x 2 mm) of Vectris were produced; 72 were covered with a 2 mm
      (thickness) layer of the Ceromer Targis and eight samples with the composite
      Tetric. All specimens were ground plane parallel with 320 Silicium carbide grit
      sandpaper in order to start with the same level of roughness. Then the specimens
      were finished and polished using the following methods: (1) Artglass toolkit, (2)
      pumice-stone and brushes/linen brush and polishing paste P3, (3) Robinson
      brush/Ivoclar Universal paste and wool brush, (4) Silicone wheel and rag wheel,
      (5) Shofu Rainbow set, (6) Sof-Lex discs, (7) Vivadent Politip set and (8) Nupro
      pastes and brushes. The surface roughness was determined with a profilometer. The
      arithmetical roughness value Ra was calculated. From each group one specimen was
      randomly chosen and sputtered with gold in order to observe the surface with a
      scanning electron microscope to evaluate its smoothness. The methods were ranked
      as followed: 2, 3 and 5 with the lowest roughness, then 8, 6, 7, 4, 1. The best
      ranked chair-side method (5) and the best ranked lab-side methods (2, 3) did not
      differ significantly between the Ra values. No difference was observed between
      the composite Tetric and the ceromer Targis when these materials were polished
      using the same method. CONCLUSION: the lab-side-methods 2 and 3 and the chair
      side-method 5 can be recommended for finishing and polishing the new ceromer
      material Targis.

PMID- 10080319
TI  - Masticatory performance and chewing experience with implant-retained mandibular
      overdentures.
AB  - The relationship between masticatory performance and chewing experience has not
      yet been explored for patients with implant-retained overdentures. Although many
      relationships have been found between parameters of objective and subjective oral
      function, the structure of these relationships remain unclear. Therefore, we
      studied in a randomized clinical trial the relationship between the comminution
      of an artificial test food, i.e. masticatory performance, and the subjective
      chewing experience. The trial involved a comparison between two groups receiving
      implant treatment and one group receiving conventional complete dentures (CD).
      The implant treatment involved either a mainly implant-supported mandibular
      overdenture on a transmandibular implant (TMI) or an implant-tissue-supported
      mandibular overdenture on two IMZ implants (IMZ). Masticatory performance as well
      as chewing experience were substantially better for the implant-retained
      overdentures compared with the complete denture group. No significant differences
      emerged between the TMI and the IMZ group. A multiple regression analysis did not
      provide any comprehensibility in the relationship between masticatory performance
      and the variables of chewing experience. In the linear structural relation
      analysis (LISREL) no direct relationship was found between masticatory
      performance and functional complaints mandibular denture. The results show that
      an improvement in masticatory performance does not imply the same improvement in
      chewing experience and vice versa.

PMID- 10080320
TI  - A survey of U.K. centres on implant failures.
AB  - This study investigated the experience of endossoseus implants in the U.K. - how
      success rates compare with other countries; the common causes of failure; early
      detection, definition and treatment of the failing implant. Information was
      gathered by means of a questionnaire sent to 120 centres in the U.K. Thirty-nine
      centres responded to the survey, reporting on a total of 5328 implants which had
      been placed over an average time period of 6.5 years. A mean failure rate of 4.3%
      was reported in the mandible with 16% in the maxilla. The survey showed that 11
      different implant systems were in use and that implants were used to support an
      overdenture in 56% of cases, and bridgework in 26%. The definition of the failing
      implant and the causes of failure were unclear, with a wide range of opinions
      given. A combination of methods were used to treat the failing implant including
      surgical techniques and chemotherapeutic agents, but the long-term success of
      these treatments was uncertain. Failure rates especially in the maxilla at some
      of the centres appear higher than have been previously suggested in the U.K. or
      abroad. Universal agreement on the criteria for 'success' and 'failure' of
      fixtures is needed along with agreed treatment protocols for the failing implant.

PMID- 10080321
TI  - Experimental study of the damping behaviour of IMZ implants.
AB  - Measurements of the damping behaviour of dental implants with the Periotest
      device are considered to be an objective means to assess the mobility of
      implants. The effects of the position of an implant in the maxilla or mandible,
      the period of time passing between the measurements and implant placement and the
      height at which the Periotest measurements are performed on the damping behaviour
      of implants have been discussed controversially. This experimental study examined
      the influence of the use of different measuring devices, the measuring height and
      the embedding depth on the damping behaviour of IMZ implants. The implants were
      embedded in resin at different depths and damping measurements were carried out
      at different measuring heights. It was found that the values rose with an
      increasing measuring height and a decreasing embedding depth. Analysis of
      variance was used to assess the influence of the embedding depth and revealed
      that the embedding depth had a significant impact on the measuring values at each
      measuring height, above 6 mm. Moreover, it was found that the higher the
      measuring height, the higher the measured values and the greater the differences
      between the values obtained at the individual depths. The different measuring
      devices had no influence on the measuring results (P = 0.79). The results of this
      study suggest that a longitudinal follow-up of the peri-implant residual bone
      height around individual implants is possible. Single measuring values by
      themselves do not allow any conclusions about the prognosis of an implant. The
      assessment of the peri-implant bone height through Periotest measurements is
      conceivable only when a table of damping values taking into account the physical
      length of the implant, the embedding depth and the measuring height for the
      examined implant system is available. In cylindrical implants, the head of the
      available prefabricated measuring post can be recommended as a constant measuring
      point for further studies, especially when the results are to be compared with
      those obtained by other study groups.

PMID- 10080322
TI  - Energy-based evaluation of occlusion.
AB  - The purpose of this study was to establish an index for evaluating occlusal
      conditions using energy levels. For this purpose, first, the movement of
      mastication under five occlusal conditions in which the positional relationship
      varied mesiodistally was simulated and the energy applied to the food being
      masticated was calculated, based on theoretical values of computing mechanics
      using finite element static analysis. As a model experiment, the energy generated
      under each occlusal condition was then measured using the electrical output from
      an occlusion pressure sensor composed of pressure-sensitive rubber. By comparing
      the theoretical values of computing mechanics and the measured values, the
      changes in the energy level under occlusal conditions were consistent with the
      trends, and the maximum value of the energy was obtained under the occlusal
      condition of Angle Class I and consisting of rigid interdigitation. In
      conclusion, our results demonstrated that occlusal conditions can be evaluated
      using the energy level as an index.

PMID- 10080323
TI  - Electromyographic examination of jaw muscles in relation to symptoms and
      occlusion of patients with temporomandibular joint disorders.
AB  - Clinical/occlusal scores and jaw-muscle EMGs were recorded in 24 TMD symptomatic
      (group S) and 20 normal (group N) subjects to evaluate the significance of EMG
      parameters and their clinical associations. Results indicated: (1) integrated EMG
      activity (IEMG) was larger at the rest position (RP) in anterior temporalis (Ta)
      but smaller at maximal voluntary clenching (MVC) in masseter (Ma) and Ta, and the
      ratios of IEMG at 70%MVC to the corresponding bite force (70%BF) were greater in
      group S; (2) mean power frequency (MPF) were almost the same in both groups but
      its shift was more rapid in group S; (3) silent period duration (SPD) was longer
      in group S; (4) asymmetry indices for SPD and silent period latency (SPL) were
      larger in group S; (5) muscle pain was associated negatively with IEMG at MVC and
      70%BF but positively with IEMGs at RP and 70%MVC, and impaired jaw movements were
      associated negatively with the above EMG values; (6) muscle pain was positively
      associated with SPD in Ma, while joint pain and sound showed positive and
      negative associations with SPD, respectively; (7) associations between occlusion
      and EMG parameters were found more in group N. These findings verify: (1) jaw
      elevators in TMD may have hyper-tonic activities and a weak functional
      efficiency; (2) jaw muscles in TMD may become easily fatigued following a
      functional effort, and less relaxed following a muscle twitch; (3) the severity
      of pain could not be reflected in EMG activities, but impaired jaw movement may
      increase tonic activity and decrease functional effort; (4) TMD symptoms may
      alter the functional adaptation of jaw-muscle activities and occlusion.

PMID- 10080324
TI  - The influence of finishing time on the marginal seal of a resin-modified glass
      ionomer and polyacid-modified resin composite.
AB  - The aim of this study was to compare the effect of immediate and delayed
      finishing on the microleakage of encapsulated resin-modified glass-ionomer, Fuji
      II LC and a polyacid-modified resin composite, Dyract compomer at both the enamel
      and dentine margins. Standardized Class V cavities were prepared along the
      cemento-enamel junction on buccal and palatal surfaces of 24 freshly extracted
      non-carious premolars. Equal numbers of buccal and palatal cavities in each group
      were restored with Fuji II LC and Dyract compomer following the manufacturer's
      instructions. The groups with delayed finishing were restored 1 week earlier,
      stored in saline at 37 degrees C and finished on the same day as the groups with
      immediate finishing. The specimens were then thermocycled 500 times and subjected
      to dye penetration testing. The results showed that both materials leaked more at
      the dentine than enamel margins for both regimes of finishing methods. There was
      no statistical difference in the microleakage of Dyract finished immediately or
      later at enamel and dentine margins and Fuji II LC finished immediately or later
      in dentine. However, a statistical difference existed between the microleakage in
      Fuji II LC finished immediately and later in enamel.

PMID- 10080325
TI  - The relationship between satisfaction with mouth and number, position and
      condition of teeth: studies in Brazilian adults.
AB  - The objective of this study was to analyse adults' subjective perception of
      satisfaction in relation to number, position and condition of natural teeth.
      Subjective perception of satisfaction was assessed by interview. Dental status
      was assessed. Two types of survey were carried out in Brazil: a longitudinal and
      a cross-sectional survey. The longitudinal study commenced in 1990, with 227
      dentate people aged 45-54 years, of two social classes. Of the 227 subjects
      examined in 1990, 126 were re-examined and interviewed 3 years later. The cross
      sectional survey used the same methods used for the longitudinal study. Six
      hundred and fifty-seven dentate males aged from 35 to 54 years were examined and
      interviewed. There was a positive correlation between satisfaction and position
      of teeth. Premolar pairs had a higher correlation with satisfaction in both
      studies. Anterior teeth were the most significant predictors of satisfaction.
      There was no difference in the percentage of satisfied persons between the
      baseline and follow-up studies. The results indicate that adults with three
      premolar pairs and intact anterior sextants were satisfied with their oral
      status. Keeping a certain number of teeth, depending on their position and
      condition, gave more satisfaction than having the missing teeth replaced with
      partial dentures.

PMID- 10080326
TI  - Factors influencing dental students to attend for eye examination.
AB  - This investigation sought to determine those factors influencing dental students
      to attend for eye examination together with the frequency of such tests and level
      of eyesight correction. A questionnaire was constructed and circulated to all
      clinical dental students attending lectures and practical classes in Dundee over
      a 1-week period. This ascertained the age and sex of the respondents and gathered
      information on what had prompted each individual to attend for eye examination.
      The knowledge of any visual problems and their correction was also ascertained.
      All 114 questionnaires that were distributed were completed. The mean elapsed
      time interval since the last eye examinations was 1.81 (standard deviation =
      1.19) years. The frequency of attendance was not affected by gender. Those who
      had had their eyesight corrected were significantly (P < 0.01) more likely to
      attend for examination every 2 years than those without correction. Good eyesight
      is important for the practice of dentistry and, although this is well recognized,
      it is apparent that the need for regular testing has not been understood by all.
      Strenuous efforts should be made to ensure that this message is impressed upon
      dental undergraduates from an early stage in their careers so that they may
      undergo screening every 2 years throughout their professional careers.

PMID- 10080327
TI  - Mastication, deglutition and speech considerations in prosthodontic
      rehabilitation of a total glossectomy patient.
AB  - Prosthetic rehabilitation of a total glossectomized patient and specifications of
      the appliance, which differs from those previously reported, are presented. The
      functional considerations and logic used to design such a device are described.
      Speech performance of the patient with and without the prosthesis, is compared
      with a perceptibility test. Improvement of the functions of mastication,
      swallowing and speech were found acceptable.

PMID- 10080328
TI  - The effect of diabetes mellitus on histopathological changes in the denture
      supporting tissues under continuous mechanical pressure in rat.
AB  - The histopathological changes in denture-supporting tissues of streptozotocin
      induced diabetes mellitus rat were studied in relation to continuous mechanical
      pressure exerted through an experimental denture base. The experimental dentures
      were designed to load continuous mechanical pressures (3.4, 1.5 or 0.5 kPa) to
      the hard palate of the molar region of a rat. From the results of this study, the
      following conclusions were drawn: the streptozotocin-induced diabetic condition
      (1) tended to prolong the appearance period of a shortened epithelial ridge, and
      weakened the phenomenon, (2) reduced the appearance period and severity of the
      compression of epithelium, (3) delayed the time of manifestation of the
      proliferative change in the recovery process of the shortened epithelial ridge,
      and weakened the phenomenon, (4) prolonged the appearance period of the
      compressed lamina propria mucosae, and enhanced the phenomenon, (5) reduced the
      number of osteoclasts, (6) lowered the threshold for induction of the
      osteoclastic bone resorption to between 1.5 and 0.5 kPa, (7) inhibited the
      appearance of osteoblast which follows the disappearance of osteoclasts, (8) did
      not induce any inflammatory change, and (9) tended to enhance the longitudinal
      change of the continuous mechanical pressure. The histopathological changes in
      the denture-supporting tissues of the streptozotocin-induced diabetes mellitus
      rat related highly to the longitudinal change of the continuous mechanical
      pressure exerted through the denture base. From the results of this study, it was
      suggested that the streptozotocin-induced diabetic condition lowers the tolerance
      of the denture-supporting tissues to continuous mechanical pressure.

PMID- 10080329
TI  - Cataract surgery: a different perspective.

PMID- 10080330
TI  - Cataract, cost: curious questions.
AB  - An investigation of the pricing of implantable prosthetic devices in Australia
      reveals some alarming practices. A governmental mechanism exists to prop up the
      pricing of 7500 listed devices to levels that are unacceptably high by world
      standards. Private hospitals and doctors are able, legally, to profit by marking
      up the cost of these devices from the market price to this artificially inflated
      price. Even the open market prices of implantable prosthetic items, such as intra
      ocular lenses, are high by international standards. In a time of budgetary
      constraint for health spending and rapidly increasing use of these devices, these
      issues urgently need to be addressed in Australia.

PMID- 10080331
TI  - Diabetic retinopathy and nephropathy in Fiji: comparison with data from an
      Australian diabetes centre.
AB  - BACKGROUND: As part of a project to improve diabetes care in Fiji, we assessed
      the magnitude of problems posed by diabetic retinopathy in that country and
      compared the findings with those from an Australian diabetes centre. The
      relationship between diabetic retinopathy and nephropathy was also examined in a
      subset of patients. METHODS: A medical team from Australia screened a total of
      446 type 2 diabetic patients (ethnicity: Fijian/Indian 16/84%) for diabetic
      retinopathy in five towns from the Division of Viti Levu, Fiji. The findings were
      compared with data obtained from 1659 type 2 diabetic patients who had attended
      an Australian diabetes centre (ethnicity Indian/ Anglo-Celtic 12/88%). In both
      cohorts, retinopathy was assessed by direct fundoscopy and a spot urine sample
      was collected for determination of albuminuria (defined as a concentration > 50
      mg/L). RESULTS: The prevalence of diabetic retinopathy increased linearly with
      duration of diabetes. It was higher in Fiji, even when cases from the same
      ethnicity (i.e. Indians) and duration were compared (P < 0.05). Extrapolation of
      the data points suggests a delay in the diagnosis of diabetes in Fiji. Of those
      patients with retinopathy in Fiji, more than half had moderate to severe non
      proliferative diabetic retinopathy or proliferative diabetic retinopathy,
      significantly higher than patients in the Australian cohort (chi2 = 29.2; P <
      0.0001). Retinopathy was not a predictor of albuminuria in Fijian Indians (chi2 =
      0.4; P = 0.5). In contrast, Australian Indians with retinopathy had significantly
      more albuminuria (chi2 = 10.2; P = 0.001). CONCLUSIONS: Severe diabetic
      retinopathy is common in both ethnic groups in Fiji. A delay in the diagnosis of
      diabetes as well as poor glycaemic control are possible factors. The availability
      of laser therapy is important to prevent loss of vision, but it is also essential
      that appropriate training of health professionals is integrated with a programme
      of diabetic complication screening to support this form of therapy.

PMID- 10080332
TI  - Therapeutic sclerokeratoplasty versus therapeutic penetrating keratoplasty in
      refractory corneal ulcers.
AB  - PURPOSE: To assess the efficacy of newer surgical technique of sclerokeratoplasty
      in cases of refractory corneal ulcers of the cornea and to compare it with
      therapeutic penetrating keratoplasty. METHODS: A randomized, prospective clinical
      trial in 20 eyes with refractory corneal ulcers was undertaken. Ten eyes each
      underwent sclerokeratoplasty (group I) or therapeutic penetrating keratoplasty
      (group II). Infections were considered cured if there was no evidence of corneal
      infiltration for 1 month following keratoplasty. Postoperative complications,
      visual acuity (VA), keratometry and graft status were evaluated with both the
      procedures after a minimum follow up of 1 year. RESULTS: Postoperative
      complications included epithelial defects, shallow anterior chamber, uveitis and
      secondary glaucoma, which were present following both procedures, with no
      significant difference in the frequency of complications between the two
      techniques (P < 005), Graft clarity and VA with both procedures were comparable.
      Significantly reduced astigmatism of < 1 D was seen in six eyes in group II in
      comparison with group I, where astigmatism of > 1.5 D was present in six eyes.
      Two eyes in group II developed re-infection, of which one was re-operated on, and
      the other developed endophthalmitis. CONCLUSIONS: Sclerokeratoplasty is a useful
      alternative to therapeutic penetrating keratoplasty in cases of refractory
      corneal ulcers with optimum clinical and useful visual outcome.

PMID- 10080333
TI  - Ipsilateral rotational autokeratoplasty for the management of corneal opacities.
AB  - PURPOSE/BACKGROUND: Penetrating keratoplasty is the logical solution for the
      management of corneal opacities. In situations such as in Papua New Guinea, where
      donor corneal tissue is scarce and corneal opacities are plenty, an alternative
      procedure for the management of corneal opacities in the form of ipsilateral
      rotational autokeratoplasty was considered. METHODS: In the present prospective
      study, ipsilateral rotational autokeratoplasty was performed in 17 eyes over a 2
      year period in a general hospital. The patient's cornea was trephined
      eccentrically and the corneal opacity was dialed out of the visual axis and was
      replaced by clear peripheral cornea. RESULTS: Most opacities were leucomata
      (76.4%). The average size of the opacity was 5.1 mm and the corneal button size
      was 7 mm.A final visual acuity of 6/18 or better was obtained in 64.7% of cases
      (at 12 months). No significant postoperative complications were encountered. No
      complex formula was needed to calculate the size of the button and, by simply
      adding 3 mm to the pupillary diameter in standard illumination, one could make an
      estimation of the graft diameter. CONCLUSIONS: Rotational autokeratoplasty has a
      definite role in places where donor corneal tissue is scarce, in patients in whom
      long-term steroids are a risk or in situations where follow up of patients is
      difficult. Rejection is a theoretical impossibility, but late endothelial failure
      could occur, requiring regrafting. Rotational autokeratoplasty should be
      seriously considered as an alternative to conventional penetrating keratoplasty.

PMID- 10080334
TI  - Orbital malignancy in Papua New Guinea: a 21 year review.
AB  - BACKGROUND: Information about orbital malignancies in Papua New Guinea (PNG) is
      limited to reports published 20 years ago. The present retrospective study was
      performed to establish the pattern of malignant orbital lesions occurring in PNG
      and to see whether the pattern is any different from that reported in the earlier
      series and in other countries. Papua New Guinea is special in that it has a large
      and relatively homogenous population unaffected,to a large extent, by contact
      with the'outside world'. METHODS: The records of 176 proven cases of orbital
      malignancy treated between 1975 and 1996 were studied with respect to type of
      tumour, age, gender; mode of presentation and, where possible, treatment and its
      outcome. RESULTS: Orbital tumours were found to be uncommon relative to other
      malignancies. The most common orbital tumour encountered in the present study was
      orbital extension of retinoblastoma (40.3%). These tumours were all unilateral
      and were associated with a very high mortality. No bilateral or familial cases
      were seen. Squamous cell carcinomas were the second most common tumours (25.6%)
      and were seen in young adults (average age 36.6 years). Basal cell carcinomas
      (9.1%) occurred later (average age 54 years) and were more common in the lighter
      skinned Southern Highlanders and expatriates. The other malignancies seen
      included lacrimal gland tumours (3.4%), malignant melanomas (4.5%), lymphomas
      (3.4%), rhabdomyosarcomas (1.7%), meibomian cell carcinomas (1.7%) and soft
      tissue sarcomas. CONCLUSIONS: Most patients presented late and the mortality rate
      was high. This could also reflect the relative paucity of ophthalmic and
      oncological services in the country as well as psychosocial attitudes to disease.
      Many patients live far from medical services and may be treated by traditional
      healers before coming to a hospital.

PMID- 10080335
TI  - Subconjunctival fat prolapse.
AB  - PURPOSE: Subconjunctival orbital fat prolapse has been rarely described in the
      literature and is frequently confused with other conjunctival tumours, such as
      dermolipoma. The purpose of the present study was to describe the clinical
      features and treatment of a series of patients with subconjunctival orbital fat
      prolapse. METHODS: Review of clinical records. RESULTS: Twelve patients with
      subconjunctival orbital fat prolapse were identified. Eight had a superotemporal
      prolapse and five of these were bilateral. All but one were male and most were
      elderly and tended to be obese. Five of these patients underwent surgical
      excision of the prolapsed fat for symptoms of discomfort or for cosmesis. Four
      atypical unilateral cases were seen in younger patients with fat prolapse
      occurring superonasally in three and inferiorly in one. In one case there was a
      history of trauma CONCLUSIONS: Subconjunctival orbital fat prolapse typically
      occurs superotemporally in obese elderly males and is easily differentiated from
      other lesions, such as dermolipoma. The prolapsed orbital fat may be excised via
      the conjunctiva.

PMID- 10080336
TI  - A randomized phase II trial of interferon-alpha2b versus 5-fluorouracil after
      trabeculectomy.
AB  - PURPOSE: The aim of the present study was to investigate the safety and potential
      efficacy of subconjunctival interferon-alpha2b (IFN-alpha), either alone or in
      combination with 5-fluorouracil (5-FU), in reducing the risk of failure of
      glaucoma surgery METHODS: A prospective, masked randomized phase II study was
      undertaken in which patients received three subconjunctival injections per week
      for 3-4 weeks postoperatively. Three treatments were compared: (i) IFN-alpha (1 x
      10(6)IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-alpha and
      5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of
      intra-ocular pressure without further surgery; and (ii) the incidence of side
      effects. RESULTS: Fifty-seven patients undergoing glaucoma surgery with an
      increased risk of failure were evaluated, including 23 patients (40%) undergoing
      trabeculectomy combined with extracapsular cataract extraction as well as other
      conventional high-risk groups. With 53 patients (93%) completing 2 years follow
      up,there was no significant difference in success rates among the three groups.
      Intra-ocular pressure was controlled without further surgery in 79% of patients
      (95% confidence interval (CI): 61, 97%) receiving IFN-alpha, in 89% of patients
      (76, 100%) receiving 5-FU and in 89% of patients (76, 100% receiving BOTH. Side
      effects were similar among the three groups. CONCLUSIONS: These results are
      consistent with a beneficial effect of IFN-alpha2b given either alone or in
      combination with 5-FU after glaucoma filtering surgery. However, the lack of a
      clear and substantial benefit over conventional anti-fibrotic therapy does not
      support the further clinical evaluation of these treatments.

PMID- 10080337
TI  - Late infection of hydroxyapatite orbital implants.
AB  - BACKGROUND: Exposure and minor complications of hydroxyapatite orbital implants
      are common. Infection appears to be rare and fibrovascular ingrowth into
      hydroxyapatite implants may make infection and extrusion less likely than with
      other types of orbital implant. METHODS: We describe three cases of chronic low
      grade infection of hydroxyapatite implants, occurring late after apparently
      uncomplicated surgery, with tiny or inapparent areas of conjunctival loss or
      exposure. RESULTS: Two of the three cases grew Staphylococcus oureus on culture.
      All three implants ultimately needed to be removed. A characteristic histological
      pattern was seen, with abrupt transition between vascularized and abscessed
      implant. CONCLUSIONS: Chronic infection of hydroxyapatite implants can occur
      late, in the absence of large conjunctival defects, or other obvious risk
      factors. While exposure of the implant to pathogens through a breach in the
      conjunctiva may have been a factor, it appeared that the infection may have
      arisen in an avascular portion of the implant prior to the conjunctival breakdown
      in one or more of these cases.

PMID- 10080338
TI  - Contact or immersion technique for axial length measurement?
AB  - PURPOSE: The purpose of the present study was to determine whether contact and
      immersion A-scan techniques produce comparable measures of the magnitude of eye
      axial length. METHOD: A prospective study in which 225 consecutive patients
      scheduled for cataract surgery in a private day surgery setting had axial lengths
      measured with an Alcon Ocuscan machine (Alcon Australia, Frenchs Forest, NSW,
      Australia) using both contact and immersion techniques. Twelve patients had both
      techniques repeated on a separate occasion. RESULTS: Measurements of eye axial
      length obtained by the immersion technique averaged 0.1 mm longer than those
      obtained by the contact technique. A difference in axial length values was
      confirmed in eyes subjected to repeated measurements. CONCLUSIONS: Both
      techniques give consistent results, but the difference between axial lengths
      measured by the two techniques has implications for choice of intra-ocular lens
      power.

PMID- 10080339
TI  - Different faces of the white cataract: a phaco surgeon's perspective.
AB  - PURPOSE: To develop a system of categorizing white cataracts so that the salient
      features, as would be pertinent to phaco-emulsification surgery, could be
      recognized pre-operatively. METHODS: Patients with total cataracts were carefully
      evaluated using slit-lamp biomicroscopy and slit-lamp photography. An attempt was
      made to determine whether pre-operative evaluation could ascertain the presence
      or absence of features of these cataracts that often cause surgical difficulties,
      namely, increased intralenticular pressure (ILP), milky cortex and brown nuclear
      colour. RESULTS: Using a standardized method of biomicroscopic evaluation, it was
      found that the status of the ILP, cortex and nuclear colour could be determined
      consistently. Surgical strategies based on such a system of categorization has
      permitted white cataracts to be consistently managed using phacoemulsification.
      CONCLUSIONS: Systematic pre-operative evaluation and categorization of white
      cataracts based on the ILP, status of the cortex and nuclear colour can permit
      proper surgical planning and successful management of such cases with
      phacoemulsification.

PMID- 10080340
TI  - Systemic effects of topical ophthalmic beta-adrenoceptor antagonists.
AB  - Topical ophthalmic beta-adrenoceptor antagonists (beta-blockers) are generally
      recognized as the treatment of choice in glaucoma management due to favourable
      efficacy, safety and tolerability. Despite topical ocular administration, beta
      blockers are systemically absorbed, in relatively small amounts, through the
      nasolacrimal drainage system and can adversely affect cardiovascular and
      pulmonary function. While cardioselective beta-blockers, such as betaxolol,
      possibly confer an advantage with respect to clinical safety through their
      receptor affinity, systemic effects are also influenced by other pharmacological
      factors, including the rate and extent of systemic absorption and the extent of
      plasma protein binding. These factors are reviewed to distinguish the various
      ophthalmic beta-blockers and to explain the observed clinical differences in the
      safety profiles of these medications.

PMID- 10080341
TI  - Leber's idiopathic stellate neuroretinitis: differential diagnosis and approach
      to management.
AB  - BACKGROUND: Leber's idiopathic stellate neuroretinitis (LISN) is a relatively
      uncommon clinical entity that is characterized by optic disc oedema and
      associated macular hard exudates. A broad range of causes can produce such a
      fundus appearance. METHODS: The clinical experience of the authors is combined
      with a review of the pertinent literature to describe the features of LISN and
      its differential diagnosis. CONCLUSION: A knowledge of the potential causes of
      neuroretinitis is important in order to formulate an effective management
      strategy.

PMID- 10080342
TI  - Clinicopathological report: mucinous carcinoma of the eyelid.
AB  - BACKGROUND: Mucinous carcinoma of the skin is a rare tumour that may involve the
      peri-ocular region. METHODS/RESULTS: A case report is presented of a 73-year-old
      woman with a right upper lid tumour, initially diagnosed as a basal cell
      carcinoma. Excisional biopsy of the residual tumour revealed mucinous carcinoma.
      Re-examination of the original pathology proved to be mucinous carcinoma,
      originating in the eyelid skin. Further treatment involved wide local resection
      and reconstruction. Systemic investigations were undertaken to exclude the
      possibility of metastatic mucinous carcinoma. CONCLUSION: This case is presented
      to alert ophthalmologists to the occurrence of this tumour in the periocular
      region, to highlight the importance of surgical excision with wide margins and
      the need for systemic investigation to exclude a primary malignancy in other
      sites, in particular the gastrointestinal system and breast.

PMID- 10080343
TI  - Lacrimal gland abscess: two case reports.
AB  - BACKGROUND: Bacterial dacryoadenitis is rare and suppuration leading to abscess
      formation within the lacrimal gland has been very rarely reported in the
      antibiotic era. METHODS: The medical records and investigation results, including
      computed tomography (CT), of two patients with lacrimal gland abscess were
      reviewed. RESULTS: Two cases of lacrimal gland abscess, one a 28-year-old male
      and the other a 64-year-old female, are described. Both demonstrated a
      characteristic low-density area within an enlarged lacrimal gland on CT. The
      first case had been treated with antibiotics and the abscess, when drained, was
      sterile. The second case settled spontaneously. Neither patient suffered any
      sequelae of dry eye. CONCLUSIONS: Although rare, lacrimal gland abscess may still
      occur and may require surgical drainage if spontaneous resolution does not occur.

PMID- 10080344
TI  - Optic disc topographic changes post-trabeculectomy visualized by anaglyphs.
AB  - BACKGROUND: Publications on changes of optic disc topography usually illustrate
      their findings with two-dimensional images. METHODS: With the introduction of
      computerized imaging, anaglyphs of stereo images can be produced for
      illustrations. Anaglyphs are viewed three-dimensionally with red-green spectacles
      that are included in refraction sets and are normally used to assess phoria. An
      anaglyph of progressive, glaucomatous progression is included to demonstrate the
      method, along with conventional colour images. RESULTS: We present two cases of
      severely altered optic disc topography post-trabeculectomy and illustrate these
      cases with anaglyphs that can be viewed three-dimensionally. CONCLUSION: Three
      dimensional viewing of illustrations assists with the visualization, perception
      and interpretation of optic disc changes.

PMID- 10080345
TI  - Massive squamous cell carcinoma of the conjunctiva.

PMID- 10080346
TI  - Cytomegalovirus retinitis in transition.

PMID- 10080347
TI  - Congenital blocked tear ducts: avoidance of probing.

PMID- 10080348
TI  - The role of venom citrate.

PMID- 10080349
TI  - Lysine 49 phospholipase A2 proteins.
AB  - The structures of several K49 PLA2 proteins have been determined and these differ
      as a group in several regions from the closely related D49 PLA2 enzymes. One
      outstanding difference is the presence of a high number of positively charged
      residues in the C-terminal region which combined with the overall high number of
      conserved lysine residues gives the molecule an interfacial adsorption surface
      which is highly positively charged compared to the opposite surface of the
      molecule. Although some nucleotide sequences have been reported, progress in
      obtaining active recombinant proteins has been slow. The K49 proteins exert
      several toxic activities, including myotoxicity, anticoagulation and edema
      formation. The most studied of these activities is myotoxicity. The myotoxicity
      induced by the K49 PLA2 proteins is histologically similar to that caused by the
      D49 PLA2 myotoxins, with some muscle fiber types possibly more sensitive than
      others. Whereas it is clear that the K49 PLA2 myotoxins lyse the plasma membrane
      of the affected muscle cell in vivo, the exact mechanism of this lysis is not
      known. Also, it is not known whether the toxin is internalized before, during or
      after the initial lysis or ever. The K49 PLA2 toxins lyse liposomes and cells in
      culture and in the latter, the PLA2 myotoxins exert at least two distinct
      mechanisms of action, neither of which is well-characterized. While the K49 PLA2
      proteins are enzymatically inactive on artificial substrates, the toxins cause
      fatty acid production in cell cultures. Whether the fatty acid release is due to
      the enzymatic activity of the K49 PLA2 or stimulation of tissue lipases, is
      unknown. While there may be a role for fatty acid production in one mechanism of
      myotoxicity, a second mechanism appears to be independent of enzymatic activity.
      Although we are beginning to understand more about the structure of these toxins,
      we still know little about the precise mechanism by which they interact with the
      skeletal muscle cell in vivo.

PMID- 10080350
TI  - Toxic effects, pharmacokinetics and clearance of saxitoxin, a component of
      paralytic shellfish poison (PSP), in cats.
AB  - Saxitoxin (STX) was the first known and most studied toxic component of paralytic
      shellfish poisoning (PSP). This toxin blocks neuronal transmission by binding to
      the voltage-gated Na+ channel. Although the toxin's mechanism of action is well
      known at the molecular level, there are still many unresolved questions about its
      pharmacokinetics and the PSP intoxication syndrome in mammals. Some of these
      questions are addressed in the present paper, which describes an experimental
      design which allowed us to follow the dynamics of STX poisoning in vivo. Adult
      cats were anaesthetized and permanently coupled to artificial ventilation, they
      were then intravenously injected with Low (2.7 microg of STX/kg) and high doses
      (10 microg of STX/kg) of toxin. Cardiovascular parameters such as blood pressure
      and electrocardiograms were recorded, urine and blood samples were collected
      during the four hours of experimental time. In order to quantify mass amount of
      STX, we used the post-column derivatization HPLC method. Urine and blood samples
      were cleansed using a C-18 Sep-Pack cartridge and ultrafree microcentrifuge
      filters. At the end of each experiment, the animals were killed and tissue
      samples from brain, liver, spleen and medulla oblongata were extracted to measure
      the amount of STX. As compared to control period, Low doses of STX made no
      difference in hemodynamics parameters. In contrast, high doses drastically
      reduced blood pressure, produced myocardial failure and finally cardiac arrest.
      Administration of 2.5 microg/kg x min of dobutamine restored hemodynamics
      parameters and allowed the animal to overcome the shock. With high doses, the
      calculated STX renal clearance in cats is 0.81 ml/min x kg(-1). This valued
      corresponds to 20.25% of the reported inulin renal clearance. Nevertheless with
      Low doses the STX renal clearance is 3.99 ml/min x kg(-1). This data suggest that
      in cats with normal cardiovascular parameters and diuresis, the STX excretion
      mainly involves glomerular filtration. During experimental time, no PSP toxins
      other than STX was detected in the body fluids and tissue samples analyzed,
      indicating that the mammals can not metabolize this molecule. STX was found in
      intensely irrigated organs such as the liver and spleen but also in the central
      nervous system (brain and medulla oblongata), showing that STX was capable of
      crossing the blood brain barrier.

PMID- 10080351
TI  - Cloning of a cDNA encoding a nerve growth factor precursor from the Agkistrodon
      halys Pallas.
AB  - Based on the high conservation in the 5' and 3' untranslated regions of NGF
      cDNAs, oligonucleotides complementary to all these known sequences were
      synthesized. By RT-PCR, we successfully isolated the complementary DNA encoding
      NGF precursor from the Agkistrodon halys Pallas (a Chinese snake strain). The
      nucleotide sequence which presents 90.5%, 88.6% and 63.4% homology to that of
      Krait Bungarus multicinctus, cobra and human NGF respectively, encoded a prepro
      NGF molecule with 241 amino acids and a mature NGF molecule with 119 amino acids.
      The NGF cDNA inserts were subcloned into pCDNA3 expression vector and then
      transfected into COS-7 cells. The supernatant of the transfected cells turned out
      NGF biological activity as assayed by the survival rate of PC12 pheochromocytoma
      cells.

PMID- 10080352
TI  - Detection of Clostridium perfringens alpha toxin using a capture antibody ELISA.
AB  - Clostridium perfringens phospholipase C (PLC), commonly known as alpha toxin, is
      the lethal, dermonecrotic toxin produced by all strains and is considered a major
      virulence factor in clostridial myonecrosis. We developed a capture antibody
      ELISA that accurately and specifically quantitates alpha toxin produced by C.
      perfringens. Another PLC, derived from Bacillus cereus, and culture filtrates
      from various bacterial species including Clostridium bifermentans and Clostridium
      novyi were not cross-reactive in this ELISA. Standard curves generated with
      homogenous C. perfringens alpha toxin revealed detection limits of 19 ng/ml. The
      ELISA was more sensitive in detecting alpha toxin than techniques such as PLC
      enzymatic activity and mouse lethality assays.

PMID- 10080353
TI  - 1H NMR study of robustoxin, the lethal neurotoxin from the funnel web spider
      Atrax robustus.
AB  - Robustoxin, the lethal neurotoxin from the Sydney funnel web spider Atrax
      robustus, is a polypeptide of 42 residues cross-linked by four disulfide bonds.
      This paper describes the sequence-specific assignment of resonances in the 1H
      nuclear magnetic resonance spectrum of robustoxin in aqueous solution. Several
      broad backbone amide resonances were encountered in spectra recorded at 27
      degrees C, making the assignments at that temperature incomplete. In spectra
      recorded at lower temperatures these amide resonances became sharper, but others
      that were sharp at 27 degrees C became broad, indicative of conformational
      averaging on the millisecond timescale for certain regions of the structure.
      Nevertheless, it was possible to establish that robustoxin contains a small,
      triple-stranded, antiparallel beta-sheet and several reverse turns, but no alpha
      helix. These observations indicate that this toxin may adopt the inhibitor
      cystine knot structure found in polypeptides from a diverse range of species,
      including a number of spiders. Analysis of the pH dependence of the spectrum
      yielded pKa values for Tyr22 and Tyr25, one of the three carboxyl groups, and the
      Lys residues.

PMID- 10080354
TI  - Molecular cloning and genomic analysis of TsNTxp: an immunogenic protein from
      Tityus serrulatus scorpion venom.
AB  - A non-toxic protein (TsNTxP) from Tityus serrulatus scorpion venom has been shown
      to be an efficient immunogen and anti-TsNTxP antibodies recognize and neutralize
      the effect of Tityus serrulatus venom [Chavez-Olortegui et al., 1997. Toxicon 35,
      213-221]. With the purpose of studying the organization of the gene that code for
      this protein, we have isolated a full length cDNA clone for TsNTxP from a cDNA
      expression library using anti-TsNTxP antibodies. The nucleotide sequence of the
      gene that encodes TsNTxP was also obtained and it reveals the presence of an
      intron within the signal peptide sequence. The TsNTxP gene showed high degree of
      similarity with genes encoding toxins from scorpions of the genus Tityrus.

PMID- 10080355
TI  - Covalent structures of BmK AS and BmK AS-1, two novel bioactive polypeptides
      purified from Chinese scorpion Buthus martensi Karsch.
AB  - Complete amino acid sequences of two novel bioactive polypeptides, each
      containing 66 amino acid residues, BmK AS and BmK AS-1 purified from the venom of
      Chinese scorpion Buthus martensi Karsch, have been determined by Edman sequencing
      and mass spectrometry on native proteins, reduced and S-carboxymethylated
      proteins and their peptides obtained after cleavage with proteolytic enzymes.
      Sequence analysis showed 86.4% structural identity between BmK AS and BmK AS-1
      and also a high sequence similarity between BmK ASs and AaH IT4, a unique anti
      insect toxin and a ligand of Na+ channels obtained from Sahara scorpion A.
      australis Hector, but poor sequence homology between BmK ASs and those of the
      known alpha-, beta-type and long-chain insect-selective type scorpion
      neurotoxins. The positions of four disulfide bridges in BmK AS-1 were established
      as Cys-12 and Cys-62, Cys-16 and Cys-37, Cys-23 and Cys-44, and Cys-27 and Cys
      46, which are the same as those in alpha- and beta-scorpion neurotoxins. These
      results suggest that BmK ASs and AaH IT4 may form a new group sharing similar
      structural and functional properties in the family of scorpion neurotoxic
      polypeptides.

PMID- 10080356
TI  - Unique toxic peptides isolated from sawfly larvae in three continents.
AB  - D-Amino acid containing peptides have been found to be responsible for sawfly
      larvae poisoning in many parts of the world. These compounds, unique in the
      animal kingdom, were isolated from three different species of sawfly indigenous
      to Australia, Denmark and South America. The octapeptide, lophyrotomin, is the
      major toxin in the Australian and Danish species and is present in small amounts
      in the South American sawfly. Pergidin, the main toxin in the South American
      sawfly, is a heptapeptide containing a phosphoseryl residue. This, as far as we
      are aware, is the first example of such a peptide to be isolated from an animal
      source. Small amounts of pergidin have been found in the other two species. All
      available evidence suggests that both peptides are biosynthesised 'de novo'
      possibly as a protective device, however it cannot be excluded that
      microorganisms may be responsible. These compounds are stable to enzymatic
      breakdown because of their configuration and their strong chemical bonding and
      lipophilic character provide a potential for residues to remain in the host
      animal and cause significant changes.

PMID- 10080357
TI  - The neuromuscular action of Ancylometes sp. spider venom in the rat phrenic nerve
      diaphragm preparation.
AB  - The effects of Ancylometes sp. venom on muscle contraction and bioelectrical
      potentials were investigated in the rat phrenic nerve diaphragm muscle
      preparation. The venom (50 microg/ml) depolarized the diaphragm muscle fiber
      membranes. This effect was abolished by tetrodotoxin and by reduction of the
      sodium concentration of the Tyrode solution. The increase in the frequency of
      miniature end plate potentials induced by the venom was also suppressed by
      tetrodotoxin (3 microM). These results indicate that the venom may activate
      voltage-dependent sodium channels in cell membranes. All of the effects of
      Ancylometes sp. venom on this nerve muscle preparation (i.e. increase in twitch
      tension, spontaneous small phasic contractions and increase in the frequency of
      miniature end-plate potentials) may be explained in terms of its action on sodium
      channels.

PMID- 10080358
TI  - Neutralization, by a monospecific Bothrops lanceolatus antivenom, of toxic
      activities induced by homologous and heterologous Bothirops snake venoms.
AB  - A monospecific Bothrops lanceolatus antivenom, currently used in Martinique, was
      tested for its efficacy in the neutralization of several toxic and enzymatic
      activities of the venoms of B. lanceolatus, B. atrox and B. asper. When tested by
      the i.p. route in mice, B. lanceolatus venom had an LD50 of 12.8 microg/g. In
      addition, it induced local tissue damage (hemorrhage, edema and myotoxicity) and
      showed indirect hemolytic activity, but was devoid of coagulant effect on human
      plasma in vitro and of defibrinating activity in mice. Antivenom was fully
      effective in the neutralization of lethal, hemorrhagic, edema-forming, myotoxic
      and indirect hemolytic effects of B. lanceolatus venom in assays involving
      preincubation of venom and antivenom. When tested against the venoms of B. asper
      and B. atrox, the antivenom completely neutralized the lethal, hemorrhagic,
      myotoxic and indirect hemolytic effects, and was partially effective in
      neutralizing edema-forming activity. In contrast, the antivenom was ineffective
      in the neutralization of in vitro coagulant and in vivo defibrinating effects
      induced by these two venoms.

PMID- 10080359
TI  - Bibliography of toxinology.

PMID- 10080360
TI  - Psychological aspects of in vitro fertilization: a review.
AB  - This paper reviews psychological research within the context of in vitro
      fertilization (IVF). The focus will be on psychological reactions before entering
      an IVF-procedure, during an IVF-treatment, and after both unsuccessful and
      successful IVF. The effects of psychosocial factors on the treatment outcome
      after IVF and interventions on conception rates will also be discussed.
      Undergoing an IVF-treatment is an emotional and physical burden, for both the
      woman and her partner. Research results suggest that couples entering an IVF
      treatment program are, in general, psychologically well adjusted. Concerning
      reactions during the treatment, both women and men experience waiting for the
      outcome of the IVF-treatment and an unsuccessful IVF. as most stressful. Common
      reactions during IVF are anxiety and depression, while after an unsuccessful IVF,
      feelings of sadness, depression and anger prevail. After a successful IVF
      treatment, IVF-parents experience more stress during pregnancy than 'normal
      fertile' parents. Mothers with children conceived by IVF express a higher quality
      of parent child relationship than mothers with a naturally conceived child.
      Research further suggests that psychosocial factors, like ineffective coping
      strategies, anxiety and/or depression are associated with a lower pregnancy rate
      following IVF-procedures. In addition, support has been found suggesting that
      stress reduction through relaxation training or behavioral treatment improves
      conception rates.

PMID- 10080361
TI  - Structuring the meaning of hope in health and illness.
AB  - The purpose of this paper is to describe a conceptual model for hope that
      captures the personal meaning of this construct within the context of health and
      illness. To identify this model, a research tool was created based on the
      semantic differential technique, a well-validated and often used approach for
      quantifying personal or connotative meaning. This tool was distributed in the
      form of a questionnaire to a voluntary sample (n = 550), consisting of three
      primary subsamples: a healthy adult subsample (n = 146), a chronic and life
      threatening illness subsample (n = 159) and a nursing subsample (n = 206). A
      multidimensional structure for the concept, Hope, was identified, using principal
      components analysis. Three primary factors defined this structure: personal
      spirit (personal dimension), risk (situational dimension) and authentic caring
      (interpersonal dimension). Personal spirit, a dominant factor, is characterized
      by a holistic configuration of hope elements, revolving around a core theme of
      meaning. Risk is primarily a predictability factor, targeted with an underlying
      component of boldness. The authentic caring factor has a substantial credibility
      component, linked with the theme of comfort. Three distinctive features
      characterize this model: (a) its ability to capture the dynamic qualitative
      experience of hope within a holistic multidimensional quantitative framework, (b)
      its representation of hope as a location in three-dimensional space and (c) its
      sensitivity to individual and group variability. This integrative model deepens
      our understanding of the experience of hope within health and illness at the
      theoretical, clinical and methodological levels.

PMID- 10080362
TI  - Local knowledge and treatment of malaria in Agusan del Sur, The Philippines.
AB  - Information about local knowledge of malaria, its transmission, treatment and
      prevention were gathered at the outset of a Malaria Control Program in order to
      incorporate this information into community interventions. Data were collected
      using focus groups and indepth interviews with caretakers of children who had had
      a recent episode of malaria. These were supplemented as baseline data through a
      survey and the ongoing participation of researchers in the intervention. Local
      knowledge of malaria was influenced by clinical diagnosis and was based on the
      coexistence of signs of illness. People conventionally self-medicated or used
      herbs for symptomatic relief prior to seeking clinical diagnosis and treatment,
      with treatment delay influenced by the logistic difficulties within the region,
      direct and indirect costs associated with treatment seeking, and delays in the
      return of results once a blood film for diagnosis was made. People were familiar
      with mosquito control activities conducted by the Malaria Control Service and, as
      a result, most respondents associated malaria with mosquitos. However, the role
      of the mosquito as the sole vector, and the means by which malaria was
      transmitted, were not well appreciated.

PMID- 10080363
TI  - Learning from unreliability: the importance of inconsistency in coping dynamics.
AB  - The role of response stability in the measurement of coping is examined with a
      focus on the unique information that can be gleaned from low test retest
      reliability ('inconsistency'). Data from two studies are presented in which a
      card sort measure of coping flexibility was used on people with three different
      chronic diseases and the elderly (n = 219). We begin by testing the hypothesis
      that the low stability reflects unreliability due to measurement artifacts, such
      as random error, low ecological validity, long test retest interval, surrogate
      assistance, or error due to completing the questionnaire in multiple sittings.
      Our findings suggest that surrogate assistance in completing questionnaires was
      the only measurement artifact associated with low stability. We then tested the
      proposition that low stability reflects a genuine behavior pattern (i.e.
      inconsistency). Hierarchical modeling revealed that measurement artifact
      accounted for less than one percent of the variance in inconsistency in reported
      coping behavior and that an additional 21% of the variance could be explained by
      the behavioral factors, including neuropsychological problems (9%), psychological
      morbidity (4%), locus of control (3%) and eudaimonistic well-being (5%). Thus
      inconsistency in reported coping behavior was better explained by behavioral and
      psychosocial factors than by the tested measurement artifacts. We conclude that
      inconsistency in reported coping behavior does indeed reflect a meaningful
      behavior pattern, rather than simply measurement artifact.

PMID- 10080364
TI  - Hierarchies and cliques in the social networks of health care professionals:
      implications for the design of dissemination strategies.
AB  - Interest in how best to influence the behaviour of clinicians in the interests of
      both clinical and cost effectiveness has rekindled concern with the social
      networks of health care professionals. Ever since the seminal work of Coleman et
      al. [Coleman, J.S., Katz, E., Menzel, H., 1966. Medical Innovation: A Diffusion
      Study. Bobbs-Merrill, Indianapolis.], networks have been seen as important in the
      process by which clinicians adopt (or fail to adopt) new innovations in clinical
      practice. Yet very little is actually known about the social networks of
      clinicians in modern health care settings. This paper describes the professional
      social networks of two groups of health care professionals, clinical directors of
      medicine and directors of nursing, in hospitals in England. We focus on network
      density, centrality and centralisation because these characteristics have been
      linked to access to information, social influence and social control processes.
      The results show that directors of nursing are more central to their networks
      than clinical directors of medicine and that their networks are more
      hierarchical. Clinical directors of medicine tend to be embedded in much more
      densely connected networks which we describe as cliques. The hypotheses that the
      networks of directors of nursing are better adapted to gathering and
      disseminating information than clinical directors of medicine, but that the
      latter could be more potent instruments for changing, or resisting changes, in
      clinical behaviour, follow from a number of sociological theories. We conclude
      that professional socialisation and structural location are important
      determinants of social networks and that these factors could usefully be
      considered in the design of strategies to inform and influence clinicians.

PMID- 10080365
TI  - Value added to health by pharmacists.
AB  - The aim of the study was to discover to whom the pharmacy profession adds value
      and how it describes and documents that value, to inform other health care
      professionals of that value, and to present a method of review. Definitions of
      'values' and 'value' were used to develop this methodology. Three ranking terms
      (benefit, demand, satisfaction) and three whom-value-serves labels (individual,
      institution, society) were chosen. Whom-value-serves label(s) were assigned to
      each article within the core matrix. The search years were 1984 to 1995. The
      articles were analyzed using the Matrix Method. From this matrix template,
      further in-depth analyses were completed. Of 86 articles on the core matrix, one
      fourth were published in medically-related journals. An article could have more
      than one whom-value-serves label. As a percentage of total whom-value-serves
      designations the 'institution' labels were prominent. Within the 'individual'
      labels, patient and pharmacist groups were identified equally. The 'society'
      label had no strong emphasis. The core matrix articles revealed the pharmacy
      profession adds value to hospital/retail organizations and the profession. It
      describes value in terms of cost containment, provision of services, and quality
      of care. Our intent is to inform health care professionals that our conceptual
      framework and methodology will be useful.

PMID- 10080366
TI  - Social relations: network, support and relational strain.
AB  - We introduce a conceptual framework with social relations as the main concept and
      the structure and the function of social relations as subconcepts. The structure
      of social relations covers aspects of formal relations and social network. The
      function of social relations covers social support, social anchorage and
      relational strain. We use this conceptual framework to describe social relations
      in the Danish population, with questionnaire data from the Danish Longitudinal
      Health Behaviour Study including a random sample of each of the age groups 25-,
      50-, 60-and 70-year olds, N = 2,011. The postal questionnaires were answered by a
      random sample in each of the age groups. The results show marked age and gender
      differences in both the structure and the function of social relations. The
      social network, measured as weekly contacts, weakens with age and so does
      instrumental support. Emotional support is unrelated to this decline in contact
      frequency and appears to be at the same level for younger and older individuals.
      Relational strain, measured as conflicts, declines with age for all kinds of
      social relations. The weakening of the social network with age does not seem to
      affect the level of emotional support and in turn seems to be partly compensated
      for by a simultaneous decline in relational strain.

PMID- 10080367
TI  - Short stature and the age of enrolment in Primary School: studies in two African
      countries. The Partnership for Child Development.
AB  - This study compares age at enrolment in Primary School with a range of
      nutritional measures for 8-9 year old and 12-13 year old children in Ghana (n =
      1566) and Tanzania (n = 1390). The results show that short stature (height-for
      age z-score), but not other nutritional variables (weight-for-age and weight-for
      height z-scores and haemoglobin concentration), is strongly associated with late
      enrolment. This relationship holds for both age group, sexes and countries, and
      is independent of socio-economic status in Tanzania (where this parameter was
      assessed). The relationship between stature and age-appropriate grade becomes
      less marked with progression through school, which is compatible with a higher
      drop out rate for more stunted children. These results suggest an important role
      for health in education; that stunted children enrol later in school and are more
      likely to drop out earlier.

PMID- 10080368
TI  - Reducing coronary heart disease in the Australian Coalfields: evaluation of a 10
      year community intervention.
AB  - Coronary heart disease is a leading cause of death in Australia with the
      Coalfields district of New South Wales having one of the country's highest rates.
      Identification of the Coalfields epidemic in the 1970's led to the formation of a
      community awareness program in the late 1980's (the healthy heart support group)
      followed by a more intense community action program in 1990, the Coalfields
      Healthy Heartbeat (CHHB). CHHB is a coalition of community members, local
      government officers, health workers and University researchers. We evaluate the
      CHHB program, examining both the nature and sustainability of heart health
      activities undertaken, as well as trends in risk factor levels and rates of
      coronary events in the Coalfields in comparison with nearby local government
      areas. Process data reveal difficulties mobilising the community as a whole;
      activities had to be selected for interested subgroups such as families of heart
      disease patients, school children, retired people and women concerned with family
      nutrition and body maintenance. Outcome data show a significantly larger
      reduction in case fatality for Coalfields men (although nonfatal heart attacks
      did not decline) while changes in risk factors levels were comparable with
      surrounding areas. We explain positive responses to the CHHB by schools, heart
      attack survivors and women interested in body maintenance in terms of the meaning
      these subgroups find in health promotion discourses based on their embodied
      experiences. When faced with a threat to one's identity, health discourse
      suddenly becomes meaningful along with the regimens for health improvement.
      General public disinterest in heart health promotion is examined in the context
      of historical patterns of outsiders criticising the lifestyle of miners, an
      orientation toward communal rather than individual responsibility for health
      (i.e. community 'owned' emergency services and hospitals) and anger about risks
      from environmental hazards imposed by industrialists.

PMID- 10080369
TI  - Income and health: what is the nature of the relationship?
AB  - The aim of this article is to examine the relationship between income and
      morbidity, both before and after controlling for other socio-economic variables.
      We use data from the Health and Lifestyle Survey (first wave), a national sample
      survey of adults, aged 18 upwards, in England, Wales and Scotland, conducted in
      1984-1985. In total, 9003 interviews were achieved. We examine the shape of the
      relationship between household equivalised income and height, waist-hip ratio,
      respiratory function (FEV1), malaise, limiting longterm illness. These indices of
      morbidity, both self-reported and measured, are approximately linearly related to
      the logarithm of income, in all except very high and low incomes (this means that
      increasing income is associated with better health, but that there are
      diminishing returns at higher levels of income). A doubling of income is
      associated with a similar effect on health, regardless of the point at which this
      occurs, providing this is within the central portion (10-90%) of the income
      distribution. The effect of income on the health measures is comparable to that
      of the other socio-economic variables in combination. The shape of the
      relationship found between income and health is compatible with worse health in
      countries with greater income inequality, without the need to postulate any
      direct effect of income inequality itself.

PMID- 10080370
TI  - A primer of magnetic stimulation as a tool for neuropsychology.
AB  - Transcranial magnetic stimulation (TMS) offers the neuropsychologist a 'virtual
      lesion' method of investigating the effects of cortical dysfunction. Classical
      neuropsychology relies on patients with irreversible, and often diffuse brain
      lesions and these factors place limitations on the inferences that can be drawn
      about normal brain function. Thus the neuropsychologist is constrained by the
      extent to which the damaged brain undergoes reorganisation and by the inability
      to address questions regarding the timing of cognitive functions. TMS can disrupt
      cognitive functions for a few tens of milliseconds (although some effects of TMS
      can be seen for longer), with spatial resolution in the order of a centimetre and
      therefore allows one to study the role of brain areas without the masking effects
      of cortical reorganisation. The spatial and temporal resolutions are not unique
      to TMS but because TMS can be used as a temporary interference technique, it has
      a functional resolution with which one can address questions beyond the range of
      other neuroimaging and patient studies. Here we outline how TMS produces
      transitory 'lesion' effects, examine how the effects of stimulation spread in
      depth and breadth across the cortex and discuss the principles of the use of TMS
      in neuropsychology. Finally, we also itemise some issues of safety.

PMID- 10080371
TI  - Two periods of processing in the (circum)striate visual cortex as revealed by
      transcranial magnetic stimulation.
AB  - To determine the timing of visual processing in the (circum)striate visual
      cortex, we examined the effect of single pulse transcranial magnetic stimulation
      over the occipital pole of healthy subjects who were engaged in a forced-choice
      visual letter identification task. Single letters, subtending a visual angle of
      0.35 degrees, were foveally presented for 10 ms and were immediately followed by
      a mask. We investigated 30 different delays (d), defined as the time between the
      onset of the visual stimulus and the onset of the magnetic stimulus, from d = 
      100 ms to d = +190 ms, and 4 different midsagittal coil positions (x), defined as
      the distance between the lower edge of the coil and the upper edge of the inion,
      from x = 1 cm to x = 7 cm. Three out of four subjects showed three distinct delay
      intervals (dips) at which application of TMS resulted in an impairment of the
      task. The first dip was centred around d = -50 ms and occurred independently of
      the coil position; the second dip was centred around d = 0 ms and was elicitable
      only with the two lowest coil positions; the third dip was centred around d = 100
      ms and was also elicitable only with the lower coil positions. In the fourth
      subject, only the first and the third dip were found. We conclude that there are
      two distinct periods when the activity in the (circum)striate visual cortex is
      necessary for the identification of visually presented letters.

PMID- 10080372
TI  - Corticospinal excitability is specifically modulated by motor imagery: a magnetic
      stimulation study.
AB  - Transcranial magnetic stimulation (TMS) was used to investigate whether the
      excitability of the corticospinal system is selectively affected by motor
      imagery. To this purpose, we performed two experiments. In the first one we
      recorded motor evoked potentials from right hand and arm muscles during mental
      simulation of flexion/extension movements of both distal and proximal joints. In
      the second experiment we applied magnetic stimulation to the right and the left
      motor cortex of subjects while they were imagining opening or closing their right
      or their left hand. Motor evoked potentials (MEPs) were recorded from a hand
      muscle contralateral to the stimulated cortex. The results demonstrated that the
      excitability pattern during motor imagery dynamically mimics that occurring
      during movement execution. In addition, while magnetic stimulation of the left
      motor cortex revealed increased corticospinal excitability when subjects imagined
      ipsilateral as well as contralateral hand movements, the stimulation of the right
      motor cortex revealed a facilitatory effect induced by imagery of contralateral
      hand movements only. In conclusion, motor imagery is a high level process, which,
      however, manifests itself in the activation of those same cortical circuits that
      are normally involved in movement execution.

PMID- 10080373
TI  - Transcranial magnetic stimulation can measure and modulate learning and memory.
AB  - The potential uses for Transcranial Magnetic Stimulation (TMS) in the study of
      learning and memory range from a method to map the topography and intensity of
      motor output maps during visuomotor learning to inducing reversible lesions that
      allow for the precise temporal and spatial dissection of the brain processes
      underlying learning and remembering. Single-pulse TMS appears to be adequate to
      examine motor output maps but repetitive TMS (rTMS) appears necessary to affect
      most cognitive processes in measurable ways. The results we have reviewed in this
      article indicate that rTMS may have a potential clinical application in patients
      with epilepsy in whom it is important to identify the lateralization of verbal
      memory. Single-pulse TMS can help identify changes in motor output maps during
      training, that may indicate improved or diminished learning and memory processes
      following a stroke or other neurological insult. Other evidence indicates that
      rTMS may even have the capability of facilitating various aspects of memory
      performance. From a research perspective. rTMS has demonstrated site- and time
      specific effects primarily in interfering with explicit retrieval of episodic
      information from long-term memory. rTMS may also be able to modulate retrieval
      from semantic memory as evidenced by response-time and accuracy changes after
      rTMS. All these findings suggest that the use of transcranial magnetic
      stimulation in the study of learning and memory will increase in the future and
      that it is already a valuable tool in the cognitive neuroscientists' belt.

PMID- 10080374
TI  - The selectivity and timing of motion processing in human temporo-parieto
      occipital and occipital cortex: a transcranial magnetic stimulation study.
AB  - An extrastriate visual area near the human temporo parieto occipital junction
      (TPO) may selectively mediate motion processing, while contributing little to the
      perception of color or form. This TPO area may be the human analogue of the
      monkey middle temporal (MT or V5) and medial superior temporal (MST) extrastriate
      visual areas. The selectivity of the effect of transcranial magnetic stimulation
      (TMS) on motion processing was unknown, as was the timecourse of occipital to TPO
      motion processing. In the first experiment, unilateral TMS was delivered over TPO
      50-250 ms after the onset of a random dot motion discrimination display that was
      presented in the right or left hemifield. TMS reduced the correct discrimination
      of motion direction only when it was delivered in a discrete time window 100-175
      ms following the onset of the display. TMS did not significantly affect hemifield
      spatial acuity in the same time window. In the second experiment, bilateral TMS
      delivered over occipital cortex also degraded the discrimination of motion
      defined form (MDF) in a discrete time window following the onset of a display
      presented foveally. Bilateral focal TMS delivered over TPO disrupted the
      discrimination of MDF in a time window beginning 20-40 ms later than the effect
      of TMS delivered over occipital cortex. Bilateral focal TMS delivered over TPO
      also degraded the discrimination of color-defined form, motion direction and
      color. TMS can trace the timing of visual processing from occipital to
      extrastriate visual areas.

PMID- 10080375
TI  - The left dorsolateral prefrontal cortex and random generation of responses:
      studies with transcranial magnetic stimulation.
AB  - Evidence from PET studies suggests that the dorsolateral prefrontal cortex
      (DLPFC) is involved in generation of random responses. We used TMS to examine the
      specific role of this area in random generation of responses, a task which
      requires holding information 'on line', suppression of habitual or stereotyped
      response patterns, intrinsic response generation, monitoring of responses and
      modification of production strategies. From the results of a previous study of
      the effects of TMS on random number generation, we proposed a network modulation
      model, whereby suppression of habitual responses is considered a key process of
      random response generation and is achieved through the modulatory influence of
      the left DLPFC over an associative network distributed in the superior temporal
      cortex. The aim of the present study was to further investigate the generality of
      this model by examining the effects of short trains of TMS over the left or right
      DLPFC or medial frontal cortex on random letter generation in healthy
      participants. TMS over the left DLPFC significantly increased non-randomness
      relative to control no stimulation trials, which was not obtained with TMS over
      the right DLPFC or medial frontal cortex. The results suggest the generality of
      network modulation model of random response generation.

PMID- 10080376
TI  - Phosphenes and transient scotomas induced by magnetic stimulation of the
      occipital lobe: their topographic relationship.
AB  - Transcranial magnetic stimulation (TMS) of the visual cortex is known to induce
      phosphenes and is able to suppress visual perception. To address the topographic
      relationship of phosphenes and transient scotomas, the visual field of 10 normal
      subjects was investigated using a perimetric approach. The central visual field
      (diameter: 20 degrees) was tested at 32 sites. Perceptual thresholds were
      determined by presenting 1 ms test spots flashed with varying intensity in random
      order. TMS was applied with a focal figure-of-eight coil placed over the inion.
      All subjects perceived phosphenes, mostly restricted to one of the lower
      quadrants within the visual field. In 13 out of 15 investigations, a magnetic
      stimulus triggered 100 ms after the visual target resulted in a relative scotoma
      with threshold changes of 8 dB or more. In 9 of 13 investigations, scotomas
      coincided spatially with sketches of phosphenes made by subjects in a separate
      test. Scotomas covered only a small percentage of the total visual field, which
      may explain the failure of previous studies to find perceptual suppression with
      the focal coil. The present result demonstrates that phosphenes evoked during TMS
      can serve as a guide for optimal visual stimulus alignment in neuropsychological
      experiments.

PMID- 10080377
TI  - Role of the prefrontal cortex in the control of express saccades. A transcranial
      magnetic stimulation study.
AB  - Single pulse transcranial magnet stimulation (TMS) was applied in five subjects
      during a saccadic gap task, i.e. with a temporal gap of 200 ms between the
      extinguishing of the central fixation point and the appearance of the lateral
      target. In all subjects, a significant increase of contralateral express saccades
      was found when TMS was applied over the dorsolateral prefrontal cortex (DPFC) at
      the end of the gap of 200 ms. Earlier stimulation over the DPFC during the gap
      had no significant effect. Furthermore, stimulation over the posterior parietal
      cortex with the same time intervals, and stimulation during a no gap task had no
      significant influence on express saccades. These results suggest that TMS is
      capable of interfering specifically with the functioning of the DPFC, probably by
      inhibition of this region. Possibly such stimulation of the DPFC reduces the
      inhibition by this region onto the superior colliculus, which results in a
      facilitation of express saccades.

PMID- 10080378
TI  - Transcranial magnetic stimulation and neuroplasticity.
AB  - We review past results and present novel data to illustrate different ways in
      which TMS can be used to study neural plasticity. Procedural learning during the
      serial reaction time task (SRTT) is used as a model of neural plasticity to
      illustrate the applications of TMS. These different applications of TMS represent
      principles of use that we believe are applicable to studies of cognitive
      neuroscience in general and exemplify the great potential of TMS in the study of
      brain and behavior. We review the use of TMS for (1) cortical output mapping
      using focal, single-pulse TMS; (2) identification of the mechanisms underlying
      neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the
      information of other neuroimaging techniques by transient disruption of cortical
      function using repetitive TMS; and finally (4) modulation of cortical function
      with repetitive TMS to influence behavior and guide plasticity.

PMID- 10080379
TI  - Imaging the brain before, during, and after transcranial magnetic stimulation.
AB  - This article provides a brief overview of current trends in combining
      neuroimaging and transcranial magnetic stimulation (TMS). First, I outline the
      utility of magnetic-resonance imaging (MRI) and frameless stereotaxy for
      planning, monitoring and documenting the location of the TMS coil relative to the
      subject's brain. Second, I describe two novel methods, based on the combination
      of TMS with positron emission tomography (PET) or with electroencephalography
      (EEG), for the assessment of connectivity and excitability of the human cerebral
      cortex. Finally, I point out the utility of PET and MRI for evaluating possible
      long-term effects of repetitive TMS.

PMID- 10080380
TI  - Localization of the human frontal eye fields and motor hand area with
      transcranial magnetic stimulation and magnetic resonance imaging.
AB  - We localized the neuroanatomical correlates for control of saccadic eye movements
      and for finger movements using a combined transcranial magnetic stimulation (TMS)
      and magnetic resonance imaging (MRI) approach. Two participants underwent TMS
      while performing an endogenous saccade task. The motor hand area was localized by
      TMS and the region anterior to it was mapped to identify the borders of a region
      where TMS produced delays in generating contralateral saccades. MRI scans were
      then obtained with fiducial markers placed over the motor hand area and 2 cm
      anterior to it, the common cortical region that produced saccadic delays in these
      two subjects. It was also shown that the structural anatomy of the hand area,
      physiologically defined by visible contractions of the contralateral hand
      following TMS, corresponded to the knob-like structure recently reported [18,
      19]. These results demonstrate that TMS can be a precise, non-invasive tool for
      neuroanatomical mapping of cortical structures when combined with structural
      images of the brain.

PMID- 10080381
TI  - Signal-, set-, and movement-related activity in the human premotor cortex.
AB  - Single unit recording studies in non-human premotor cortex have revealed neurons
      with motor-related activity. Other neurons, however, seem to be involved in prior
      movement selection and preparation processes, and have activity related to visual
      instruction signals or movement preparation ('set'). We have used single pulse
      transcranial magnetic stimulation (TMS) to identify similar processes in human
      subjects. In Experiment 1 subjects performed a cued movement task while being
      stimulated with TMS over three sites: sensorimotor cortex, posterior premotor
      cortex and anterior premotor cortex. TMS slowed movements when applied at 140 ms
      after the visual cue over the anterior premotor site, at 180 ms after the visual
      cue over the posterior premotor site, and at 220 ms and later after the visual
      cue over the sensorimotor cortex. The results are consistent with a change from
      signal to movement-related processing when moving from premotor to motor cortex.
      In Experiment 2 there was a preparatory set period between the instruction signal
      that informed subjects which movement to make and the 'go' signal that informed
      them when to actually make the movement. TMS was applied over the anterior
      premotor site and the sensorimotor site during the set period. At both sites TMS
      had similar effects on slowing subsequent movements. The results suggest set
      activity in both premotor and motor cortices in human subjects.

PMID- 10080382
TI  - The role of the parietal cortex in visual attention--hemispheric asymmetries and
      the effects of learning: a magnetic stimulation study.
AB  - Our previous studies of the role of the parietal cortex in visual learning and
      attention showed that the right parietal cortex is required for normal
      performance on conjunction visual search tasks but that its role depends on
      whether subjects are naive or trained on the task. Here we extend these findings
      in two Experiments. Experiment 1 shows that magnetic stimulation of the left
      parietal cortex also impairs performance (measured as reaction time) on
      conjunction visual search tasks, but only when the target is present in the right
      (contralateral) visual field. Stimulation of the same region on a feature
      detection task speeds up performance significantly when the target is in the left
      (ipsilateral) visual field. Experiment 2 explores further the role of the right
      parietal cortex in learning conjunction search tasks. Stimulation of the right
      parietal cortex in subjects who had already trained on some visual search tasks
      did not impair performance on a novel motion/form conjunction task even though
      the search was clearly serial. Stimulation of area V5, however, severely
      disrupted performance on the same task. These data indicate that the role of the
      parietal cortex may change much earlier in the course of training than initially
      thought.

PMID- 10080383
TI  - What peptides these deltorphins be.
AB  - The deltorphins are a class of highly selective delta-opioid heptapeptides from
      the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first
      of these fascinating peptides came to light in 1987 by cloning of the cDNA of
      from frog skins, while the other members of this family were identified either by
      cDNA or isolation of the peptides. The distinctive feature of deltorphins is the
      presence of a naturally occurring D-enantiomer at the second position in their
      common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the
      prototype of a group of mu-selective opioids from the same source. The D-amino
      acid and the anionic residues, either Glu or Asp, as well as their unique amino
      acid compositions are responsible for the remarkable biostability, high delta
      receptor affinity, bioactivity and peptide conformation. This review summarizes a
      decade of research from many laboratories that defined which residues and
      substituents in the deltorphins interact with the delta-receptor and
      characterized pharmacological and physiological activities in vitro and in vivo.
      It begins with a historical description of the topic and presents general schema
      for the synthesis of peptide analogues of deltorphins A, B and C as a means to
      document the methods employed in producing a myriad of analogues. Structure
      activity studies of the peptides and their pharmacological activities in vitro
      are detailed in abundantly tabulated data. A brief compendium of the current
      level of knowledge of the delta-receptor assists the reader to appreciate the
      rationale for the design of these analogues. Discussion of the conformation of
      these peptides addresses how structure leads to further hypotheses regarding
      ligand receptor interaction. The review ends with a broad discussion of the
      potential applications of these peptides in clinical and therapeutic settings.

PMID- 10080384
TI  - Activity and injury-dependent expression of inducible transcription factors,
      growth factors and apoptosis-related genes within the central nervous system.
AB  - This review primarily discusses work that has been performed in our laboratories
      and that of our direct collaborators and therefore does not represent an
      exhaustive review of the current literature. Our aim is to further discuss the
      role that gene expression plays in neuronal plasticity and pathology. In the
      first part of this review we examine activity-dependent changes in the expression
      of inducible transcription factors (ITFs) and neurotrophins with long-term
      potentiation (LTP) and kindling. This work has identified particular ITFs (Krox
      20 and Krox-24) and neurotrophin systems (particularly the brain-derived
      neurotrophic factor (BDNF)/tyrosine receptor kinase-B, Trk-B system) that may be
      involved in stabilizing long-lasting LTP (i.e. LTP3). We also show that changes
      in the expression of other ITFs (Fos, Jun-D and Krox-20) and the BDNF/trkB
      neurotrophin system may play a central role in the development of hippocampal
      kindling, an animal model of human temporal lobe epilepsy. In the next part of
      this review we examine changes in gene expression after neuronal injuries
      (ischemia, prolonged seizure activity and focal brain injury) and after nerve
      transection (axotomy). We identify apoptosis-related genes (p53, c-Jun, Bax)
      whose delayed expression selectively increases in degenerating neurons, further
      suggesting that some forms of neuronal death may involve apoptosis. Moreover,
      since overexpression of the tumour-suppressor gene p53 induces apoptosis in a
      wide variety of dividing cell types we speculate that it may perform the same
      function in post-mitotic neurons following brain injuries. Additionally, we show
      that neuronal injury is associated with rapid, transient, activity-dependent
      expression of neurotrophins (BDNF and activinA) in neurons, contrasting with a
      delayed and more persistent injury-induced expression of certain growth factors
      (IGF-1 and TGFbeta) in glia. In this section we also describe results linking
      ITFs and neurotrophic factor expression. Firstly, we show that while BDNF and
      trkB are induced as immediate-early genes following injury, the injury-induced
      expression of activinA and trkC may be regulated by ITFs. We also discuss whether
      loss of retrograde transport of neurotrophic factors such as nerve growth factor
      following nerve transection triggers the selective and prolonged expression of c
      Jun in axotomized neurons and whether c-Jun is responsible for regeneration or
      degeneration of these axotomized neurons. In the last section we further examine
      the role that gene expression may play in memory formation, epileptogenesis and
      neuronal degeneration, lastly speculating whether the expression of various
      growth factors after brain injury represents an endogenous neuroprotective
      response of the brain to injury. Here we discuss our results which show that
      pharmacological enhancement of this response with exogenous application of IGF-1
      or TGF-beta reduces neuronal loss after brain injury.

PMID- 10080385
TI  - Distribution and retrograde transport of trophic factors in the central nervous
      system: functional implications for the treatment of neurodegenerative diseases.
AB  - Neurotrophins play a crucial role in the maintenance, survival and selective
      vulnerability of various neuronal populations within the normal and diseased
      brain. Several families of growth promoting substances have been identified
      within the central nervous system (CNS) including the superfamily of nerve growth
      factor related neurotrophin factors, glial derived neurotrophic factor (GDNF) and
      ciliary neurotrophic factor (CNTF). In addition, other non-neuronal growth
      factors such as fibroblast growth factor (FGF) have also been identified. This
      article reviews the trophic anatomy of these factors within the CNS.
      Intraventricular and intraparenchymal injections of exogenous nerve growth factor
      result in retrograde labeling mainly within the cholinergic basal forebrain.
      Distribution of brain derived neurotrophic factor (BDNF) following
      intraventricular injection is minimal due to the binding to the trkB receptor
      along the ventricular wall. In contrast, intraparenchymal injections of BDNF
      results in widespread retrograde transport throughout the CNS. BDNF has also been
      shown to be transported anterogradely within the CNS. Infusion of GDNF into the
      CNS results in retrograde transport limited to the nigrostriatal pathway.
      Hippocampal injections of NT-3 retrogradely label mainly basal forebrain neurons.
      Retrograde transport of radiolabeled CNTF has only been observed in sensory
      neurons of the sciatic nerve. Following intraventricular and intraparenchymal
      infusion of radiolabeled bFGF, retrograde neuronal labeling was found in the
      telecephalon, diencephalon, mesencephalon and pons. In contrast retrograde
      labeling for aFGF was found only in the hypothalamus and midbrain. Since select
      neurotrophins traffic anterogradely and retrogradely within the nervous system,
      these proteins could be used to treat neurological diseases such as Alzheimer's
      disease, Parkinson's disease and amyotrophic lateral sclerosis.

PMID- 10080386
TI  - The biosynthesis and post-translational modification of Pbs21 an ookinete-surface
      protein of Plasmodium berghei.
AB  - Radiolabelled methionine incorporation into synchronised Plasmodium berghei
      gametocytes or ookinete cultures, showed that Pbs21 is not synthesised in
      bloodstage parasites; synthesis was detected within three hours of induction of
      gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. We
      show native Pbs21 to be a hydrophobic membrane protein that was insensitive to
      cleavage by phosphatidylinositol phospholipase C (PI-PLC), but sensitive to
      alkaline hydroxylamine, and partially sensitive to glycosylphosphatidylinositol
      dependent phospholipase D (GPI-PLD) and HNO2. 3H-myristic and palmitic acid, 3H
      glucosamine and mannose incorporation indicated Pbs21 was acylated and
      glycosylated. Linkage of the acyl group was sensitive to HNO2, which released an
      acyl-phosphatidylinositol more hydrophobic than that released from P3 of
      Trypanosoma brucei. All these properties are consistent with the presence of a
      malaria-specific glycosylphosphatidylinositol (GPI) anchor. In contrast
      recombinant Pbs21 (rPbs21), expressed in Spodoptera frugiperda cells, was
      sensitive to both PI-PLC and GPI-PLD, consistent with the protein being modified
      by a different (S. frugiperda) GPI anchor. Brefeldin A blocked secretion of
      rPbs21 within a cytoplasmic reticular compartment. Following deletion of the
      putative GPI anchor addition site (amino acids 189 213), the protein was
      transported to the cell surface and secreted directly into the aqueous phase of
      the culture medium. Deletion of amino acids 205-213 disrupted Pbs21 processing,
      transport through the ER and distribution onto the cell surface. Deletion of
      amino acids 1-28 prevented transport of Pbs21 into the ER. This suggests that
      correct processing of the GPI anchor in the ER-Golgi network is essential for the
      successful secretion of the recombinant protein, which is additionally dependent
      upon an N-terminal secretory signal sequence.

PMID- 10080387
TI  - Identification of plasmenylethanolamine as a major component of the phospholipids
      of strain DM 28c of Trypanosoma cruzi.
AB  - A novel phospholipid has been purified from strain Dm 28c of Trypanosoma cruzi,
      and characterized by fast atom bombardment mass spectrometry and nuclear magnetic
      resonance spectroscopy as a plasmenylethanolamine with a hexadec-l-enyl group in
      the sn-1 position and an approximately equimolar mixture of octadecenoate and
      octadecadienoate esterified to the sn-2 hydroxyl. The purified
      plasmenylethanolamine reacted positively when probed with sera from patients with
      chronic Chagas' disease. Since plasmenylethanolamines of similar structure are
      abundant in mammalian cardiac and neuronal tissues, cross reactions between these
      epitopes may be a factor in the mechanism of autoimmune pathology in the chronic
      phase of Chagas' disease.

PMID- 10080388
TI  - Purification and partial characterization of three isoforms of serine
      hydroxymethyltransferase from Crithidia fasciculata.
AB  - Three molecular forms of serine hydroxymethyltransferase (SHMT) have been
      detected in choanomastigotes of Crithidia fasciculata by DEAE-cellulose
      chromatography. The three isoforms (named SHMT I, II, and III) presented small
      differences in charge and molecular weight. Digitonin treatment of intact cells
      suggested that SHMT III is cytosolic, whereas the other two isoforms are particle
      bound, one being mitochondrial (SHMT I) and the other one very likely glycosomal
      (SHMT II). The three SHMT isoforms were purified to homogeneity, and their
      physicochemical and kinetic properties studied. Determination of their native and
      subunit molecular masses revealed that all of them have a tetrameric structure.
      The three isoforms were shown to be PLP-dependent enzymes after L-cysteine and
      hydroxylamine hydrochloride treatments. They showed similar pH optima, bimodal
      kinetics for L-serine and Michaelis-Menten kinetics for THF.

PMID- 10080389
TI  - Alternative 2-keto acid oxidoreductase activities in Trichomonas vaginalis.
AB  - We have induced high levels of resistance to metronidazole (1 mM or 170 microg
      ml(-1)) in two different strains of Trichomonas vaginalis (BRIS/92/STDL/F1623 and
      BRIS/92/STDL/B7708) and have used one strain to identify two alternative T.
      vaginalis 2-keto acid oxidoreductases (KOR) both of which are distinct from the
      already characterised pyruvate:ferredoxin oxidoreductase (PFOR). Unlike the
      characterised PFOR which is severely down-regulated in metronidazole-resistant
      parasites, both of the alternative KORs are fully active in metronidazole
      resistant T. vaginalis. The first, KORI, localized in all membrane fractions but
      predominantly in the hydrogenosome fraction, is soluble in Triton X-100 and the
      second, KOR2, is extractable in 1 M acetate from membrane fractions of
      metronidazole-resistant parasites. PFOR and both KORI and KOR2 use a broad range
      of 2-keto acids as substrates (pyruvate, alpha-ketobutyrate, alpha-ketomalonate),
      including the deaminated forms of aromatic amino acids (indolepyruvate and
      phenylpyruvate). However, unlike PFOR neither KORI or KOR2 was able to use oz
      ketoglutarate. Deaminated forms of branched chain amino acids (alpha
      ketoisovalerate) were not substrates for T. vaginalis KORs. Since KOR I and KOR2
      do not apparently donate electrons to ferredoxin, and are not down-regulated in
      metronidazole-resistant parasites, we propose that KORI and KOR2 provide
      metronidazole-resistant parasites with an alternative energy production
      pathway(s) which circumvents metronidazole activation.

PMID- 10080390
TI  - Role of glutathione in the detoxification of ferriprotoporphyrin IX in
      chloroquine resistant Plasmodium berghei.
AB  - The reduction in hemozoin content is a well known feature of chloroquine
      resistant Plasmodium berghei. Using NK65-derived lines displaying increasing
      resistance levels, we observed an inverse relationship between the hemozoin
      content, and the glutathione (GSH) and glutathione S-transferase (GST) levels.
      Treatment of highly chloroquine-resistant-infected mice with buthionine
      sulfoximine (BSO), which has previously been shown to partially reverse this
      chloroquine resistance, led to a significant increase in hemozoin production. In
      vitro studies on the polymerization of ferriprotoporphirin IX (FPIX) at pH 5.0
      showed that GSH partially inhibited beta-hematin synthesis, while GST had a
      trivial and non specific effect. Furthermore, chloroquine-sensitive parasites
      invading reticulocytes displayed higher GSH level and GST activity, and reduced
      hemozoin synthesis and susceptibility to chloroquine. We conclude that, in
      chloroquine resistant P.berghei, GSH can detoxify hemin within the food vacuole,
      thus precluding its polymerization and preventing the activity of chloroquine and
      other quinoline-containing drugs. It is proposed that vacuolar GSH could be
      ascribed to an erythrocytic origin, since the resistant lines invade
      reticulocytes, which contain higher levels of GSH and GST than normocytes.

PMID- 10080391
TI  - Molecular characterization of a calponin-like protein from Schistosoma japonicum.
AB  - The gene for a Schistosoma japonicum (Philippine strain origin) (Sjp) calponin
      like protein has been cloned and characterised. The clone, designated P14, was
      isolated from a Sjp adult worm lambda ZAP cDNA library by immunoscreening, and
      was shown to contain a full-length cDNA encoding a 38.3 kDa protein that shared
      significant sequence similarity to a number of previously reported calponins and
      22 kDa smooth-muscle proteins. Northern analysis indicated the P14 transcript was
      approximately 2.2 kb in both Sjp and Chinese strain S. japonicum (Sjc) adult
      worms. Southern blot analysis of genomic DNA suggested that several copies of the
      P14 gene are present in the Sjc and Sjp genomes but only one copy was evident in
      the S. mansoni (Sm) genome. Western blot analysis indicated that the product of
      P14 occurs as a 38 kDa protein in adult Sjp worms and homologues are present in
      adult worms of Sjc and Sm. At least six isoforms, all with a similar molecular
      size of approximately 38 kDa and isoelectric points ranging from 8.1 to 9.5, were
      present in adult Sjc worms. The protein was immunolocalized to the muscle of male
      and female Sjc adult worms. Recombinant protein was expressed in E. coli and
      purified under denaturing conditions, and in yeast to produce a soluble protein
      in purified form. The availability of purified, correctly folded protein will
      allow investigations into its biological functions and potential involvement in
      host immunity.

PMID- 10080392
TI  - Involvement of calyculin A-sensitive phosphatase(s) in the differentiation of
      Trypanosoma cruzi trypomastigotes to amastigotes.
AB  - Differentiation of the non-dividing trypomastigote form of Trypanosoma cruzi, the
      causative agent of Chagas disease, to the dividing amastigote form normally
      occurs in cytoplasm of infected cells. Here we show that calyculin A. a potent
      inhibitor of protein phosphatases 1 and 2A, induces at pH 7.5 extracellular
      transformation of long slender trypomastigotes to round amastigote-like forms
      which acquire characteristic features observed after the normal differentiation
      process: repositioning and structural changes of the kinetoplast, release of
      surface neuraminidase, and expression of amastigote-specific epitopes. Calyculin
      A inhibits parasite phosphatases and changes in the phosphorylation of specific
      proteins occur during the transformation process. As an exposure of
      trypomastigotes to calyculin A concentrations as low as 1 nM and for only 1-2 h
      is sufficient to induce transformation, the inhibition of calyculin A-sensitive
      phosphatase(s) appears to play a major role in initiating the trypomastigote
      differentiation.

PMID- 10080393
TI  - A signal recognition particle receptor gene from the early-diverging eukaryote,
      Giardia lamblia.
AB  - The molecular mechanisms for targeting and translocation of secreted proteins are
      highly conserved from bacteria to mammalian cells, although the machinery is more
      complex in higher eukaryotes. To investigate protein transport in the early
      diverging eukaryote, Giardia lamblia, we cloned the gene encoding the alpha
      subunit (SRalpha) of the signal recognition particle (SRP) receptor. SRalpha is a
      small GTPase that functions in SRP-ribosome targeting to the ER. Sequence and
      phylogenetic analyses showed that SRalpha from G. lamblia is most homologous to
      SRalpha proteins from higher eukaryotes, although it lacks some conserved motifs.
      Specifically, giardial SRalpha has an N-terminal extension that enables SRalpha
      of higher eukaryotes to interact with a beta subunit that anchors it in the ER
      membrane. While the C-terminal regions are similar, giardial SRalpha lacks a
      prominent 13 amino acid regulatory loop that is characteristic of higher
      eukaryotic versions. Thus, giardial SRalpha resembles that of higher eukaryotes,
      but likely diverged before the advent of the regulatory loop. The 1.8 kb SRalpha
      transcript has extremely short untranslated regions (UTRs): a 1-2 nt 5'- and a 9
      nt 3' UTR with the polyadenylation signal overlapping with the stop codon. RT
      PCR, Northern and Western analyses showed that SRalpha is present at relatively
      constant levels during vegetative growth and encystation, even though there are
      extensive changes in endomembrane structures and secretory activity during
      encystation. Imnuno-EM showed that SRalpha localizes to ER-like structures,
      strengthening the observation of a typical ER in G. lamlia. Unexpectedly, SRalpha
      was also found in the lysosome-like peripheral vacuoles, suggesting unusual
      protein traffic in this early eukaryote. Our results indicate that the eukaryotic
      type of cotranslational transport appeared early in the evolution of the
      eukaryotic cell.

PMID- 10080394
TI  - Expression of a marker for intracellular Trypanosoma cruzi amastigotes in
      extracellular spheromastigotes.

PMID- 10080395
TI  - The propeptide of Fasciola hepatica cathepsin L is a potent and selective
      inhibitor of the mature enzyme.

PMID- 10080396
TI  - Deferoxamine effects on Plasmodium falciparum gene expression.

PMID- 10080397
TI  - Galectins from sheep gastrointestinal nematode parasites are highly conserved.

PMID- 10080398
TI  - Trypanosoma brucei GPEET-PARP is phosphorylated on six out of seven threonine
      residues.

PMID- 10080399
TI  - Molecular cloning of the 22-24 kDa excretory-secretory 22U protein of Dirofilaria
      immitis and other filarial nematode parasites.

PMID- 10080400
TI  - Immediate and long-term results of ATG induction therapy for delayed graft
      function compared to conventional therapy for immediate graft function.
AB  - The use of polyclonal antibodies for delayed graft function (DGF) was tested in
      83 renal allograft recipients. Conventional immunosuppression (CI) was given to
      52 patients with immediate graft function (IGF) while 31 patients with DGF
      received the polyclonal antibody ATG. Administration of OKT3 was restricted to
      steroid-resistant acute rejections in both groups. The incidence and severity of
      acute rejections, graft survival rate, CMV infections, and lymphocyte subsets
      were examined. ATG patients experienced a total of 0.6 acute rejections per
      patient, whereas CI patients had 0.9 on the average (P < 0.05). Second and third
      acute rejections occurred less frequently and later in the ATG group than in the
      CI group (P < 0.01). Steroid-resistant acute rejections occurred in 20 of the CI
      patients (38 %) but in only 7 of ATG patients (23 %). One-year graft survival in
      the CI and ATG groups was 98.1% and 93.2%, respectively. A decreased CD4 + to CD8
      + T-lymphocyte ratio of about 0.5 was still detectable 5 years after the initial
      ATG administration. Hence, patients with DGF appear to benefit from induction
      therapy with ATG.

PMID- 10080401
TI  - P-glycoprotein expression is not a useful predictor of acute or chronic kidney
      graft rejection.
AB  - Because of the role of P-glycoprotein (P-gp) in multidrug resistance (MDR), it
      has been suggested that P-gp might play a role in acute and chronic rejection
      after organ transplantation. The purpose of the present work was to investigate a
      possible relationship between graft outcome and P-gp expression on peripheral
      mononuclear cells of renal transplant recipients. We determined P-gp expression
      in 27 patients with long-term, stable graft function (ST) and in 15 patients with
      chronic deterioration of graft function (CR). In addition, 40 patients were
      studied prior to, and at intervals after, transplantation with 21 healthy
      individuals serving as controls. P-gp values were highest in healthy controls and
      in ST patients. We found no correlation between P-gp values and acute rejection.
      CR patients tended to have lower levels of P-gp expression. Our results
      contradict the opinion that an overexpression of P-gp induces acute or chronic
      rejection by inhibiting the efficacy of immunosuppressive treatment.

PMID- 10080402
TI  - Development of injury in a rat model of chronic renal allograft rejection: effect
      of dietary protein restriction.
AB  - Non-allogeneic factors such as increased nephron "workload" may contribute to
      chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was
      tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery
      recipient, "tolerised" by previous donor blood transfusions. Survival, weight
      gain, serum creatinine concentration and creatinine clearance were similar for
      both groups at all times. Urinary protein was significantly (P < 0.05) lower in
      the low-protein (LP) group 1 month after transplantation. After 3 and 6 months,
      both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy
      was significantly (P < 0.05) less in the LP group and interstitial fibrosis was
      marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular
      dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1
      mRNA expression were similarly increased in both groups. Thus, reducing dietary
      protein to 8% lowered urinary protein, but did not significantly affect the
      development of chronic rejection in renal allografts beyond affording a degree of
      protection from tubulointerstitial damage.

PMID- 10080403
TI  - Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in
      spontaneously hypertensive rats.
AB  - Renal toxicity is a serious side effect of therapy with tacrolimus (FK506), an
      immunosuppressive agent administered to renal transplant recipients. We
      investigated the effect of hepatocyte growth factor (HGF) on tacrolimus-induced
      nephrotoxicity in spontaneously hypertensive rats (SHR). After a right
      nephrectomy, rats received a continuous perfusion of either HGF in a dose of 5
      microg/kg daily (tacrolimus + HGF group) or normal saline (tacrolimus group) into
      the left renal artery at a rate of 1 microl/h for 7 days after surgery.
      Tacrolimus was injected intramuscularly in a dose of 4 mg/kg daily for 10 days
      after surgery. HGF significantly inhibited the tacrolimus-induced increase in the
      serum creatinine (SCr) level (P < 0.05). HGF also prevented the tacrolimus
      induced loss in body weight. The bromodeoxyuridine (BrdU) index was significantly
      higher in kidney specimens from the tacrolimus + HGF group. These findings
      suggest that HGF induces the regeneration of renal tubular cells and suppresses
      tacrolimus-induced renal toxicity in SHR.

PMID- 10080404
TI  - Patients benefit--partners suffer? The impact of heart transplantation on the
      partner relationship.
AB  - Terminal heart disease affects not only the patient, but also members of the
      patient's family, and especially the spouse. The aim of this prospective study of
      26 couples was to collect information about the impact of heart transplantation
      on the partner relationship. Data were collected from patients and spouses when
      the patients were placed on the waiting list for transplantation, 1 year
      postoperatively, and 5 years postoperatively. The Family Assessment Measure (FAM
      III), a self-report instrument that provides quantitative indices of family
      functioning on seven interacting dimensions, was used. In the course of the
      transplant process, both patients and spouses reported a significant
      deterioration in the partner relationship in general. While patients perceived
      only one clear-cut point of conflict communication about emotions - as crucial,
      the spouses reported a significant worsening in role performance, communication,
      emotional involvement, and values and norms. These changes were discernible 1
      year after transplantation and persisted for at least 5 years. We conclude that
      heart transplantation has a significant negative impact on the partner
      relationship 1-5 years after transplantation. Consequently, more attention should
      be paid to all aspects of the partner relationship in a holistic approach to the
      treatment of heart transplant recipients and their partners.

PMID- 10080405
TI  - Increased expression of basic fibroblast growth factor during chronic rejection
      in intestinal transplants is associated with macrophage infiltrates.
AB  - Long-term survival of intestinal transplants is hampered by chronic rejection
      (CR). Since transplants with CR demonstrate fibrotic changes, the cytokine basic
      fibroblast growth factor (bFGF) may be involved in the tissue remodelling of
      chronic intestinal rejection. The aim of this study was to investigate the bFGF
      gene and protein expression and distribution in chronically rejecting intestinal
      allografts. Orthotopic small bowel transplantation was performed in the
      allogeneic DA-to-AS rat combination. Cyclosporin was administered temporarily to
      prevent acute rejection. Controls were DA isografts and normal DA. bFGF gene
      expression was evaluated using reverse transcriptase polymerase chain reaction
      (RT-PCR) of the ileum RNA and was standardized against Glyceraldehyde-3-phosphate
      dehydrogenase (GAP-DH) expression. bFGF protein was determined using
      immunohistochemistry. To identify the bFGF-positive cell type, sequential
      sections were stained for cell markers. Allografts showed histological features
      of CR, whereas isografts preserved normal architecture. bFGF gene expression was
      present in normal ileum and significantly upregulated in allografts.
      Immunohistochemical staining showed a significant increase in bFGF protein
      compared to isografts. Most bFGF-positive cells were localized in the submucosa
      and muscularis, particularly around the neural plexus. bFGF-positive cells
      appeared to be ED-2-positive macrophages, strongly suggesting that the site of
      bFGF production is the activated macrophage. This study demonstrates increased
      bFGF mRNA and protein in chronically rejecting intestinal allografts that appear
      to be produced by macrophages.

PMID- 10080406
TI  - Exocrine, but not endocrine, tissue is susceptible to microvascular
      ischemia/reperfusion injury following pancreas transplantation in the rat.
AB  - While post-transplant pancreatitis is still a frequently occurring complication
      of whole pancreas transplantation, dysfunction of the endocrine tissue is rarely
      observed. Given that microcirculatory disorders play a major role in the
      pathogenesis of pancreatitis, we hypothesized a dissociation of endocrine and
      exocrine microvascular control in pancreas transplantation (cold ischemia
      reperfusion) and studied this dissociation quantitatively, analyzing the
      pancreatic microcirculation after heterotopic isogeneic pancreaticoduodenal
      transplantation in rats by means of fluorescence microscopy. Functional capillary
      density (FCD) of both exocrine and endocrine tissue of pancreatic grafts after 1
      h of cold storage in HTK solution did not differ when compared to sham-operated,
      time-matched controls. Intermittent capillary perfusion, which is absent under
      sham control conditions and which is proposed to be operative as a compensatory
      mechanism to counteract malperfusion, was observed in 52% of the exocrine, but in
      only 8% of the endocrine, tissue studied (p < 0.05). In contrast, cold storage of
      pancreatic grafts for 6 h in HTK resulted in a complete loss of intermittent
      capillary perfusion in exocrine tissue and, consequently, marked exocrine
      perfusion failure (decrease in FCD), while FCD of pancreatic endocrine tissue was
      preserved without any significant change in the incidence of intermittent
      capillary perfusion. Thus, our results indicate a higher susceptibility of the
      exocrine pancreas to cold ischemia/reperfusion events that is associated with
      significant alterations in nutritive perfusion and, thus, with limitations of the
      oxygen supply to the tissue. This may lead to inflammatory tissue reactions in
      the clinical setting of pancreas transplantation.

PMID- 10080407
TI  - Cytomegalovirus pneumonitis after kidney transplantation is not caused by
      plugging of cytomegalic endothelial cells only.
AB  - In addition to life-threatening pneumonia, cytomegalovirus (CMV) may also cause
      subclinical pulmonary dysfunction after kidney transplantation. To investigate
      the role of plugging of cytomegalic endothelial cells in the pulmonary capillary
      bed, we prospectively determined specific carbon monoxide diffusion capacity
      (KCOc) and its components: the pulmonary diffusing membrane factor (Dm) and
      pulmonary capillary blood volume (Vcap) before and during CMV infection in 13
      kidney transplant recipients and 13 controls. During CMV infection, mean KCOc
      decreased significantly by 28 % of the initial value (mean KCOc 79 vs 109; P <
      0.005 ) due to a decrease in both Vcap and Dm. The KCOc in controls showed a
      significantly smaller decrease due to a slightly lower Vcap. We conclude that
      kidney transplant recipients with CMV infection have significant pulmonary
      diffusion disturbances due to a combination of lower Vcap and lower Dm. The most
      likely explanation for this phenomenon is a local inflammatory process due to CMV
      and not plugging of cytomegalic endothelial cells only.

PMID- 10080408
TI  - Cadaveric small bowel/split liver transplantation in a child.
AB  - Scarcity of size-matched grafts continues to be a major limiting factor for liver
      and combined liver/intestinal transplants in the pediatric population. It is
      reported that 29% of pediatric patients listed for hepatic transplantation die
      while waiting for a donor. The reported mortality of pediatric patients awaiting
      intestinal transplantation is about 40%. We report on a technique of segmental
      liver and intestinal transplantation in a child. To our knowledge, this is the
      first report of a combined split liver-intestinal transplantation. We used a
      cadaveric donor, but the technique can also be performed with a live donor. The
      adult recipient of one segment of the liver was discharged home without
      complications. The child who received the combined liver intestinal graft
      developed intestinal perforation and severe rejection and died. If this technique
      is applied successfully, the adverse effects and mortality of a long
      pretransplant waiting period in pediatric patients may be avoided.

PMID- 10080409
TI  - Splenic artery aneurysm and orthotopic liver transplantation.
AB  - Splenic artery aneurysms are a rare but potentially fatal complication after
      liver transplantation. We report three cases presenting in a 12-month period in
      adult patients who underwent transplantation for chronic liver disease. Doppler
      ultrasound of the splenic artery should be performed in all patients with
      cirrhosis and portal hypertension who are being assessed for liver
      transplantation. The aneurysm can be ligated at the time of transplantation.

PMID- 10080410
TI  - Atypical mycobacterium infection with dermatological manifestation in a renal
      transplant recipient.
AB  - In April 1997, a 58-year-old renal transplant recipient presented with abscess
      like nodules in his left calf and on his right foot. Furuncular disease was
      suspected and the patient was treated with flucloxacillin. However, the lesions
      increased in size and became ulcerative. In the following 3 months, cultures of
      punctuated material, blood, and urine remained negative and gram stains did not
      reveal micro-organisms. In June 1997, acid-fast stains were positive. A diagnosis
      of a nontuberculous mycobacterium (NTM) infection was made and empirical
      antimycobacterial therapy was started. The combination of relatively minor
      symptoms with enlarged purulent lesions, causing severe morbidity, raises the
      possibility of NTM infection in the immunocompromised patient.

PMID- 10080411
TI  - Graft outcome after introduction of new Eurotransplant allocation system.

PMID- 10080412
TI  - Comparison of safety and efficacy of carvedilol and metoprolol in stable angina
      pectoris.
AB  - In a double-blind, randomized, 3-month multicenter study, the safety and
      tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to
      50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice
      daily in younger and elderly patients with stable angina. After a 7-day placebo
      run-in at the end of which a symptom-limited bicycle ergometric exercise was
      performed, 368 patients were randomly allocated to the parallel treatment groups.
      After 4 weeks of therapy with a low dose, a further exercise test was performed
      and patients were titrated in single-blind fashion to the higher dose if the
      increase in total exercise time was < 1 minute, and there was no safety concern.
      After a further 8 weeks of treatment a third exercise test was performed.
      Carvedilol low dose/high dose was shown to be at least as safe and well tolerated
      as metoprolol low dose/high dose both in younger and elderly patients. There were
      no hitherto unknown adverse events and no marked change in the types of events
      after increase of the doses. Early adverse events after treatment initiation or
      uptitration were equal with both medications, indicating no particular risk
      associated with carvedilol's vasodilatory action. No rebound phenomena were
      observed. Both drugs showed good antianginal and anti-ischemic efficacy, with
      marked increases on uptitration including patients > or = 65 years of age.
      However, in the doses selected, which appeared equipotent with respect to beta
      blockade, carvedilol's improvement of time to 1-mm ST-segment depression was
      statistically significantly greater than that of metoprolol. This could be due to
      its additional vasodilatory or antioxidative actions. Based on the safety and
      efficacy data of the present study, use of the higher of the 2 recommended doses
      of carvedilol and metoprolol appears justified in younger and elderly patients
      without adequate therapeutic control at lower doses.

PMID- 10080413
TI  - Generalist versus specialist care for acute myocardial infarction.
AB  - Early studies conflict regarding improved patient outcomes with cardiologist
      directed care for acute myocardial infarction (AMI). We sought to assess the
      magnitude and mechanism of the influence of physician specialty on inpatient
      mortality for AMI. Using data from the Pennsylvania Health Care Cost Containment
      Council and elsewhere, we developed age-stratified logistic regression models of
      inpatient mortality, utilizing a split sample strategy for model development and
      validation. Referral bias and physician caseload were explicitly addressed. We
      analyzed 30,351 admissions for AMI. In patients < 65 years old, the adjusted odds
      ratio (OR) for mortality with cardiologist care was 0.89 (95% confidence interval
      [CI] 0.640 to 1.24, p = 0.49) relative to generalist care. In patients > or = 65
      years of age, the adjusted OR was 0.86 (95% CI 0.72 to 1.03, p = 0.10). Caseload
      was significantly higher among cardiologists and was inversely related to
      inpatient mortality. Mortality models with caseload but not physician designation
      or physician designation without caseload found each predictor statistically
      significant in the absence of the other (OR for cardiologist care 0.82, 95% CI
      0.71 to 0.95, p = 0.007; OR for patients with low volume physicians relative to
      high volume 1.27, 95% CI 1.05 to 1.51, p = 0.014). Older patients of physicians
      with higher case loads had a lower risk adjusted inpatient mortality for AMI.
      This probably explains the trend toward better outcomes among patients of
      cardiologists rather than noncardiologists.

PMID- 10080414
TI  - Long-term prognostic importance of hyperkinesia following acute myocardial
      infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation.
AB  - The long-term prognostic importance of hyperkinesia is unknown following an acute
      myocardial infarction (AMI). The American Society of Echocardiography recommends
      that hyperkinesia should not be included in calculation of wall motion index
      (WMI). The objective of the present study was to determine if hyperkinesia should
      be included in WMI when it is estimated for prognostic purposes following an AMI.
      Six thousand, six hundred seventy-six consecutive patients were screened 1 to 6
      days after AMI in 27 Danish hospitals. WMI was measured in 6,232 patients
      applying the 9-segment model and the following scoring system: 3 for
      hyperkinesia, 2 for normokinesia, 1 for hypokinesia, 0 for akinesia, and -1 for
      dyskinesia. All patients were followed with respect to mortality for at least 3
      years. WMI was calculated in 2 different ways: 1 including hyperkinetic segments
      (hyperkinetic-WMI) and the other excluding nonhyperkinetic segments
      (nonhyperkinetic-WMI) by converting the hyperkinetic segments to normokinetic
      segments. Hyperkinesia occurred in 736 patients (11.8%). WMI was an important
      prognostic factor (relative risk 2.49; p = 0.0001) for long-term mortality
      together with heart failure, history of hypertension, angina, or diabetes,
      previous AMI, age, thrombolytic therapy, arrhythmias, and bundle branch block. In
      a multivariate analysis including nonhyperkinetic-WMI, hyperkinesia was
      associated with a relative risk of 0.84, which was statistically significant
      (confidence intervals 0.74 to 0.96; p = 0.01). When hyperkinesia was included,
      both in WMI (hyperkinetic-WMI) and as an independent variable, no additional
      prognostic information (relative risk 0.93; p = 0.26) was obtained. An
      echocardiographic evaluation shortly after an AMI gave important prognostic
      information, especially if the information concerning hyperkinesia was included.
      If WMI is used for prognostic purposes, hyperkinesia should be included in
      calculation of the index.

PMID- 10080415
TI  - Meta-analysis of exercise testing to detect coronary artery disease in women.
AB  - To determine the accuracy of the exercise electrocardiogram (ECG), exercise
      thallium, and exercise echocardiogram (echo) for the diagnosis of coronary artery
      disease in women, English language studies published between 1966 and 1995 were
      identified through a MEDLINE search. Studies that contained data on at least 50
      women who underwent both an exercise test and coronary angiography were examined.
      Studies were reviewed for sensitivity, specificity, and methodologic
      characteristics by 2 independent reviewers. Nineteen studies met the inclusion
      criteria for exercise electrocardiography, 5 studies for exercise thallium, and 3
      studies for exercise echo. The exercise ECG had a weighted mean sensitivity,
      specificity, and a likelihood ratio (LR) of 0.61 (95% confidence intervals 0.54
      to 0.68), 0.70 (0.64 to 0.75), (+) LR 2.25 (1.84 to 2.66), (-) LR 0.55 (0.47 to
      0.62), respectively. The exercise thallium had a weighted mean sensitivity,
      specificity, and LRs of 0.78 (0.72 to 0.83), 0.64 (0.51 to 0.77), (+) LR 2.87
      (1.0 to 4.96), (-) LR 0.36 (0.27 to 0.45). The exercise echo had a weighted mean
      sensitivity, specificity, and LRs of 0.86 (0.75 to 0.96), 0.79 (0.72 to 0.86),
      (+) LR 4.29 (2.93 to 5.65), (-) LR 0.18 (0.05 to 0.31). Thallium subset analysis
      revealed that studies using planar imaging were more specific than those using
      tomographic imaging. Thus, currently available exercise tests are only moderately
      sensitive and specific for the diagnosis of coronary artery disease in women.

PMID- 10080416
TI  - Relative contributions of a single-admission 12-lead electrocardiogram and early
      24-hour continuous electrocardiographic monitoring for early risk stratification
      in patients with unstable coronary artery disease.
AB  - Patients with unstable coronary syndromes are a heterogeneous group with varying
      degrees of ischemia and prognosis. The present study compares the prognostic
      value of a standard electrocardiogram (ECG) obtained at admission to the hospital
      with the information from 24-hour continuous electrocardiographic monitoring
      obtained immediately after admission. The admission ECGs and 24 hours of
      vectorcardiographic (VCG) monitoring from 308 patients admitted with unstable
      coronary artery disease were analyzed centrally regarding standard
      electrocardiographic ST-T changes, ST-vector magnitude (ST-VM), and ST change
      vector magnitude episodes. End points were death, acute myocardial infarction,
      and refractory angina pectoris within a 30-day follow-up period. ST-VM episodes
      (> or = 50 microV for > or = 1 minute) during VCG monitoring was the only
      independent predictor of death or acute myocardial infarction by multivariate
      analysis. ST-VM episodes during vectorcardiography was associated with a relative
      risk of 12.7 for having a cardiac event, hypertension was associated with a
      relative risk of 1.7, and ST depression on the admission ECG was associated with
      a relative risk of 5.7. Patients with ST depression at admission had an event
      rate (death or acute myocardial infarction) of 17% at 30-day follow-up. Patients
      without ST depression could further be risk stratified by 24 hours of VCG
      monitoring into a subgroup with ST-VM episodes at similar (8%) risk and a
      subgroup without ST-VM episodes at low (1%) risk (p = 0.00005). Continuous VCG
      monitoring provides important information for evaluating patients with unstable
      coronary artery disease. It is recommended that patients not initially estimated
      at high risk based on the admission ECG are referred for 24 hours of VCG
      monitoring for further risk stratification.

PMID- 10080417
TI  - Comparison of slow oscillating versus fast balloon inflation strategies for
      coronary angioplasty.
AB  - Previous studies suggest that slow and/or oscillating balloon inflation during
      coronary angioplasty may decrease the incidence of coronary dissection and
      improve clinical outcomes. To compare the effect of slow oscillating versus
      conventional fast inflation techniques on the incidence of severe coronary
      dissection during angioplasty, 622 patients were randomized to slow oscillating
      inflation versus fast inflation. Angiographic outcomes of the procedures and in
      hospital clinical events were recorded. The primary end point of severe (type C,
      D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and
      6.6% of patients undergoing fast inflation (p = 0.87). Major complications
      (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q
      wave myocardial infarction) occurred in 4.7% of patients undergoing slow
      oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2
      inflation strategies did not differ in the pressure at which the balloon achieved
      full expansion, angiographic success rate, residual stenosis, and incidence of
      all minor and/or major complications. We conclude that there is no benefit of
      slow oscillating inflation over routine fast inflation in angioplasty. Slow
      oscillating inflation did not dilate lesions at lower pressures, decrease the
      incidence of dissection or severe dissection, or reduce the incidence of adverse
      clinical outcomes.

PMID- 10080418
TI  - Predictors of long-term outcome after stent implantation in a saphenous vein
      graft.
AB  - Stenting of saphenous vein graft (SVG) lesions is associated with significant
      clinical events at late follow-up. We sought to determine predictors of clinical
      outcome after this procedure. One hundred twenty-eight balloon-expandable stents
      were implanted in the SVGs of 106 patients. Baseline clinical and angiographic
      characteristics were analyzed. All grafts, including those not stented, were
      scored for extent of disease involving the luminal surface of the graft, and for
      the presence of low profile lesions (< 50% graft stenosis) and/or high profile
      lesions (> or = 50% graft stenosis). The in-hospital success rate was 98.1%.
      Before discharge, no patient died, required bypass surgery, or had repeat
      angioplasty of the same graft. Follow-up was obtained on all the patients. At a
      median of 18 months, 15% had died, 17% had experienced myocardial infarction, 20%
      had required repeat bypass surgery, and 37% needed repeat angioplasty to either
      the same site or a different lesion. Event-free survival was recorded in only 44%
      of the patients. The cumulative Kaplan-Meier survival at 2.4 years was 78.7%.
      Using the Cox proportional hazards model, predictors of survival were the absence
      of a high profile lesion in any nonstented patent graft (p = 0.004), and the use
      of lipid-lowering agents at follow-up (p = 0.01). Stenting SVG lesions can be
      performed with a high degree of procedural success, but at long-term follow-up
      there is a high rate of cardiac events. The absence of a high profile lesion in
      any nonstented patent graft is the strongest predictor of survival.

PMID- 10080419
TI  - Clinical utility of negative contrast intravascular ultrasound to evaluate plaque
      morphology before and after coronary interventions.
AB  - Although intravascular ultrasound (IVUS) is used for evaluation of plaque volume
      and lumen size as well as detection of vessel wall structures after catheter
      based interventions, differentiation between the lumen and plaque structures can
      be difficult. This study attempted to evaluate the efficacy of negative contrast
      IVUS imaging for assessment of vessel wall morphology after coronary
      interventions. IVUS studies were performed in 67 lesions in 66 patients before
      and after coronary interventions. After the baseline ultrasound imaging run, warm
      5% glucose solution was injected manually through the guiding catheter into the
      coronary artery to washout blood from the lumen to avoid speckled reflections
      from red blood cells (negative contrast). Quantitative measurements were obtained
      and plaque morphology was assessed for the presence and extent of medial
      dissections and intimal flaps. There was no difference in each quantitative
      parameter between baseline images and negative contrast images. The vessel wall
      boundary was clearly delineated from the lumen, which was defined as effective
      negative contrast in 51 of 67 lesions (76%). The baseline images revealed plaque
      dissection in 9 lesions (18%) and an intimal flap in 13 lesions (25%). In
      addition, 4 dissections (8%) and 16 intimal flaps (31%) were visualized during
      the infusion of negative contrast. Additional treatment was performed in 4
      lesions (8%) based on the images with negative contrast. Negative contrast IVUS
      was more sensitive in demonstrating a plaque fracture than were baseline images.
      This method is useful for enhancing the diagnostic capability of IVUS imaging and
      may influence the decision-making process during interventional procedures.

PMID- 10080420
TI  - Usefulness of dobutamine radionuclide ventriculography for prediction of left
      ventricular function improvement after coronary artery bypass grafting for
      ischemic cardiomyopathy.
AB  - Ventricular function may improve after coronary artery bypass grafting (CABG) in
      patients with ischemic cardiomyopathy depending on the amount of contractile
      myocardial reserve. Based on the studies using dobutamine echocardiography to
      predict regional wall improvement after revascularization, we investigated the
      benefit of low-dose dobutamine radionuclide ventriculography for assessing
      functional contractile reserve in this population. The study group included 56
      patients with ischemic cardiomyopathy (mean left ventricular [LV] ejection
      fraction [EF] of 23 +/- 5%) and multivessel disease, who were referred for
      viability assessment. All underwent radionuclide ventriculography before and
      during infusion of 5 and 10 microg/kg/min of dobutamine. An increase in global
      LVEF from rest to dobutamine was calculated, and 10% was considered the cutoff
      value to predict ventricular improvement after CABG. Of the 35 patients who
      underwent CABG 1 month later, 29 were available for repeated radionuclide
      ventriculography after 12 +/- 5 months. Of these, 15 showed improvement (delta
      LVEF > or = 5%, mean 10 +/- 5%) and 14 did not (delta LVEF < 5%, mean -1 +/- 3%).
      The increase in EF with dobutamine had the highest univariate predictive value of
      all parameters evaluated. The sensitivity, specificity, and positive and negative
      predictive values of dobutamine radionuclide ventriculography were 67%, 93%, 91%,
      and 72%, respectively. We conclude that dobutamine radionuclide ventriculography
      is a useful method to assess contractile reserve and predict ventricular
      functional improvement after CABG in patients with ischemic cardiomyopathy.

PMID- 10080421
TI  - Prognostic utility of myocardial viability assessment.
AB  - Myocardial viability assessment is useful in patients with severe coronary artery
      disease and severe left ventricular dysfunction. Whereas most studies have
      focused on recovery of regional function, there are emerging data on patient
      outcome. Review of these data suggests that patients with chronic ischemia,
      cardiomyopathy, and viable myocardium who are treated medically have a worse,
      outcome than those treated with coronary revascularization. However, there are no
      prospective randomized trials. We present perspectives for future studies.

PMID- 10080422
TI  - Assessment by transesophageal echography of atherosclerosis of the descending
      thoracic aorta in patients with hypercholesterolemia.
AB  - This study assesses atheromatous lesions and aortic stiffness of the descending
      thoracic aorta (DTA) in patients with hyperlipidemia by transesophageal
      echography (TEE) and investigates the relations between atherosclerotic lesions
      and aging or serum cholesterol levels in these patients. Subjects included 16
      patients with familial hypercholesterolemia (FH), 15 non-FH hyperlipidemic
      patients (non-FH), and 17 age-matched normal subjects. With use of TEE, the DTA
      was divided into 4 longitudinal portions of equal length, and the atheromatous
      lesions of each portion of DTA were scored according to their character and
      extension by biplane 2-dimensional TEE. The scores of atheromatous lesions from
      all 4 portions were added together to give the total atheromatous score. Then,
      after measuring the instantaneous dimensional changes of DTA in a cardiac cycle
      by M-mode TEE and blood pressure (BP) by a cuff method, we calculated the aortic
      stiffness parameter beta = ln(systolic BP/diastolic BP)/([Dmaximum -
      Dminimum]/Dminimum). The beta was significantly higher in FH and non-FH subjects
      than in normal subjects. In both FH and non-FH subjects, the total atheromatous
      score correlated with total serum cholesterol levels (r = 0.64 [p <0.01]; r =
      0.58 [p <0.05], respectively). There were significant correlations between age
      and beta in all 3 groups (FH, r = 0.67 [p <0.005]; non-FH, r = 0.53 [p <0.05];
      normal subjects, r = 0.49 [p <0.05]), and the slopes of the regression lines of
      FH and non-FH subjects were much steeper than those of normal subjects. The
      incidence of atherosis in the DTA was significantly higher in hyperlipidemic
      patients than in normal subjects, even among the younger members of the
      hyperlipidemic population with progressive aortic stiffness.

PMID- 10080423
TI  - Radiofrequency ablation of atrial flutter due to administration of class IC
      antiarrhythmic drugs for atrial fibrillation.
AB  - In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI)
      due to treatment with class IC antiarrhythmic drugs. In this study, we
      prospectively investigated the effects of AFI ablation and continuation of drug
      therapy in patients with AF who developed AFI due to long-term administration of
      class IC antiarrhythmic drugs. The study population consisted of 187 patients
      from an AF registry with paroxysmal AF who were orally treated with flecainide (n
      = 96) or propafenone (n = 91). Twenty-four patients (12.8%) developed AFI during
      the course of treatment. In 20 of these patients (10.7%), electrophysiologic
      study revealed typical AFI. These patients underwent radiofrequency ablation of
      AFI. Ablation failed in 1 patient. All patients continued preexisting drug
      treatment. Recurrence of AF was assessed by ambulatory Holter monitoring and
      serial questionnaires. During a mean follow-up of 11 +/- 4 months, the incidence
      of AF episodes was significantly lower in patients with a combined therapy (2.7
      +/- 3.6 per year) than in control subjects with a sole drug treatment (7.8 +/-
      9.2 per year, p <0.05) and than before therapy (10.2 +/- 5.4 per year, p <0.001).
      Subgroup analysis revealed that 7 patients (36.8%) remained symptom free with no
      evidence of atrial tachyarrhythmia. Eight additional patients (42.1%) had ongoing
      paroxysmal AF, however, with a significantly lower incidence of AF episodes than
      before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the
      remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It
      is concluded that in patients with AF who develop typical AFI due to
      administration of class IC antiarrhythmic agents, a combined therapy with
      catheter ablation of AFI and continuation of drug treatment is highly effective
      in reducing occurrence and duration of atrial tachyarrhythmias.

PMID- 10080424
TI  - Effect of atropine on QT prolongation and torsade de pointes induced by
      intracoronary acetylcholine in the long QT syndrome.
AB  - We recently reported a marked QT prolongation and torsade de pointes (TDP)
      induced by an intracoronary acetylcholine (ACh) administration in patients with
      long QT syndrome, but the mechanism was not determined. In the present study, the
      effect of atropine on the ACh-induced QT prolongation and TDP was studied in long
      QT syndrome. Nine patients with congenital long QT syndrome were studied. ACh at
      doses of 20, 50, and 100 microg were injected in a stepwise manner into the left
      main coronary artery, and the changes in the QT interval were measured. In 4 of
      the 9 patients, ACh administration at a dose of 100 microg was repeated after an
      intravenous atropine administration at a dose of 0.5 mg. The QT intervals were
      measured using 12-lead electrocardiograms, and the data were compared before and
      after atropine administration. The coronary angiograms were normal and coronary
      spasm was not induced by ACh in all patients. The intracoronary administration of
      ACh at a dose of 100 microg significantly prolonged the corrected QT interval
      (QTc), from 511 +/- 26 to 629 +/- 40 ms (p <0.05). In 5 of the 9 patients, TDP
      was induced and was spontaneously terminated within 10 seconds (n = 4) or
      required direct-current shock (n = 1). After atropine administration,
      intracoronary ACh at the same dose resulted in no QT prolongation, and the QTc
      interval remained unchanged (525 +/- 29 vs 520 +/- 21 ms before and after
      atropine), and no TDP was induced. These findings indicate that the muscarinic
      receptor is involved in ACh-induced QT prolongation and TDP, both of which were
      prevented by the atropine administration.

PMID- 10080425
TI  - Maintenance of blood pressure control and left ventricular performance with small
      doses of enalapril.
AB  - Enalopril treatment (20 mg every 12 hours) of 24 patients with essential
      hypertension and left ventricular (LV) hypertrophy established normal blood
      pressure (BP) after 8 weeks, and after 7 years had reduced LV mass index by 39%
      from 148 +/- 34 to 90 +/- 16 g/m2, and had normalized LV structure and function
      and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20,
      10, and 5 mg/day during the eighth year caused no significant changes in BP, LV
      structure, LV systolic function, or QT dispersion, which all likewise remained
      unaltered during a further year of the 5-mg/day regimen. We conclude that for
      hypertensive patients in whom prolonged treatment with standard doses of
      enalapril has normalized BP, LV structure and function, and QT dispersion,
      significantly smaller doses are sufficient to maintain these cardiovascular
      achievements.

PMID- 10080426
TI  - Estimation of pulmonary wedge pressure by transmitral Doppler in patients with
      chronic heart failure and atrial fibrillation.
AB  - Previous studies have demonstrated that left ventricular (LV) filling pressures
      can be estimated from transmitral Doppler recording in patients in sinus rhythm
      who have a broad spectrum of cardiac diseases. However, the correlation between
      pulmonary wedge pressure (PWP) and mitral Doppler profile has not yet been
      clearly defined in patients with atrial fibrillation, particularly in the
      presence of severe LV systolic dysfunction. The aim of this study was to evaluate
      the correlations between PWP and transmitral Doppler variables in patients with
      atrial fibrillation and chronic heart failure due to dilated cardiomyopathy. PWP
      and the mitral Doppler profile were simultaneously recorded in 35 consecutive
      heart failure patients (28 men, 7 women; mean age, 69 +/- 9 years) with severe LV
      dysfunction (mean ejection fraction 22% +/- 5%). Doppler measurements were
      averaged over 10 cardiac cycles. In addition, left atrial areas were derived from
      the apical 4-chamber view. Significant relations were observed between PWP and
      several parameters derived from the mitral flow: isovolumic relaxation time (r = 
      70), acceleration rate (r = 0.78), deceleration rate (r = 0.82), and deceleration
      time (r = -0.95). However, by stepwise multivariate analysis, deceleration time
      emerged as the sole independent predictor of PWP (r2 = 0.95, F = 590). The
      analysis led to the following equation: PWP = 51 - 0.26 (deceleration time). Our
      data suggest that mitral Doppler echocardiography is a useful tool for predicting
      PWP in heart failure patients with severe LV dysfunction even in the presence of
      atrial fibrillation.

PMID- 10080427
TI  - Relation of exercise capacity to left ventricular systolic function and diastolic
      filling in idiopathic or ischemic dilated cardiomyopathy.
AB  - Although exercise intolerance is a cardinal symptom of patients with dilated
      cardiomyopathy (DC) and heart failure, the factors that limit exercise capacity
      in these patients remain a matter of debate. To assess the contribution of left
      ventricular (LV) diastolic filling to the variable exercise capacity of patients
      with DC, we studied 47 patients (60 +/- 12 years) with DC in stable mild-to
      moderate heart failure with a mean LV ejection fraction of 28%. Exercise capacity
      was measured as total body peak oxygen consumption (VO2) during symptom-limited
      bicycle (10 W/min) and treadmill (modified Bruce protocol) exercise. LV systolic
      function and diastolic filling were assessed at rest before each exercise by M
      mode, Doppler echocardiography, and radionuclide ventriculography. As expected,
      treadmill exercise always yielded higher peak VO2 than bicycle exercise (21 +/- 6
      vs 18 +/- 5 ml/kg/min, range 12 to 35 and 7 to 30 ml/kg/min, respectively, p
      <0.001). Both of these VO2 measurements were highly reproducible (R = 0.98). With
      univariate analysis, close correlations were found between peak VO2 (with either
      exercise modalities) and Doppler indexes of LV diastolic filling, as well as with
      the radionuclide LV ejection fraction. Stepwise multiple regression analysis
      identified 3 nonexercise variables as independent correlates of peak VO2, of
      which the most powerful was the E/A ratio (multiple r2 = 0.38, p <0.0001),
      followed by peak A velocity (r2 = 0.54, p <0.0001) and mitral regurgitation grade
      (r2 = 0.58, p = 0.024). In conclusion, our data indicate that in patients with
      DC, peak VO2 is better correlated to diastolic filling rather than systolic LV
      function.

PMID- 10080428
TI  - Five-year follow-up after percutaneous balloon mitral valvuloplasty in children
      and adolescents.
AB  - Balloon mitral valvuloplasty (BMV) is an effective intervention in patients with
      symptomatic mitral stenosis. However, the late results of BMV in children and
      adolescents have not been well studied. The aim of this study was to assess the
      late functional and morphologic results after BMV in children and adolescents.
      BMV was performed in 46 children and adolescents (mean age 15.5 +/- 3.2 years,
      range 7 to 19; 19 males) with rheumatic mitral stenosis. Serial clinical and
      echocardiographic evaluation was conducted to assess the long-term results of the
      procedure during a follow-up period of 66 +/- 6 months. The mitral valve score
      was 6 +/- 2/16. BMV was successful in 45 patients (98%). There was a significant
      increase of the mean mitral valve area index (MVAI) (0.65 +/- 0.14 vs 1.54 +/-
      0.23 cm2/m2, p <0.001) and a significant reduction of the mean transmitral
      pressure gradient (16.1 +/- 2.9 vs 5.1 +/- 3.1 mm Hg, p <0.001) from pre- to post
      BMV, respectively. There was no significant change of MVAI or the pressure
      gradient during the follow-up compared with immediately after BMV (1.51 +/- 0.31
      cm2/m2 and 4.9 +/- 2.5 mm Hg, respectively). No deaths or mitral valve
      replacement occurred during the follow-up period. Restenosis (loss of >50% of the
      achieved increase in MVAI) occurred in 3 patients (6.5%). All other patients
      showed persistent improvement in their New York Heart Association class (< or =
      II). Thus, the event-free survival with good functional results was encountered
      in 42 patients (91%) at the end of the follow-up period. The left atrial diameter
      decreased from 4.6 +/- 0.9 before BMV to 3.7 +/- 0.6 cm at follow-up (p <0.05).
      It is concluded that BMV has excellent intermediate-term results in children and
      adolescents with a relatively low mitral valve score.

PMID- 10080429
TI  - Association of left ventricular systolic performance and cavity size with
      angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy.
AB  - The insertion-deletion (ID) polymorphism of the angiotensin-converting enzyme
      (ACE) gene is a marker linked to differences in plasma and cardiac ACE activity
      as well as to an increased mortality in patients with idiopathic heart failure.
      We examined the possibility that ACE gene ID variants are associated with
      differences in left ventricular (LV) systolic performance or internal LV
      dimensions in a high-risk cohort of patients with idiopathic dilated
      cardiomyopathy (IDC). The ACE genotype was determined in 171 patients selected
      with IDC in New York Heart Association functional class II to III heart failure
      and with a LV ejection fraction of < or = 40%. Left ventricular performance and
      dimensions were assessed using echocardiography (n = 161) and radionuclide
      ventriculography (n = 169). The frequency of ACE gene ID alleles was not
      different in the study versus non-age-matched (n = 171; odds ratio 0.94) and age
      matched (n = 106, odds ratio 0.88) control groups. Ejection fraction was found to
      be worse in patients with the DD genotype (echocardiography, DD = 23.5 +/- 0.70,
      ID + II = 26.8 +/- 0.8, p = 0.009; ventriculography, DD = 21.7 +/- 0.9, ID + II =
      25.3 +/- 0.8, p = 0.003). LV end-systolic and end-diastolic diameters were
      increased in patients with the DD genotype. Multifactor regression analysis
      showed the ACE genotype to be an independent predictor of both ejection fraction
      (echocardiography, p <0.02; ventriculography, p <0.03) and end-diastolic diameter
      (p <0.02). In conclusion, the results of this study indicate that the DD genotype
      of the ACE gene is independently associated with both a reduced LV systolic
      performance and an increased LV cavity size in patients with IDC.

PMID- 10080430
TI  - Three-dimensional echocardiographic analysis of valve anatomy as a determinant of
      mitral regurgitation after surgery for atrioventricular septal defects.
AB  - Mitral regurgitation (MR) is a significant complication after atrioventricular
      septal defect (AVSD) surgery. The relation of the valve leaflet morphology and
      the MR mechanism remains a conundrum. Two-dimensional echocardiography depicts
      leaflet edges, whereas volume-rendered 3-dimensional echocardiography provides
      direct visualization of the surface areas of the mitral valve leaflets. This
      study examines the relation of mitral valve anatomy as determined by 3
      dimensional echocardiography with MR origins in patients after AVSD repair.
      Twenty-seven patients with AVSD surgery and Doppler color MR were prospectively
      enrolled (median age was 5 years and 16 patients had Down syndrome). Doppler
      color flow imaging of the MR jet and 3-dimensional echocardiography of the mitral
      valve were performed with a probe in the transthoracic or transesophageal
      position. Enface 3-dimensional views of the mitral valve from the left atrium
      were reconstructed. Analysis of the 3-dimensional data was possible in 21 of the
      27 patients. Mean area ratios of the 3 mitral leaflets were calculated (superior
      40 +/- 7%, inferior 35 +/- 5%, mural 25 +/- 6%). Both intra and interobserver
      variability on the area measurements were <5%. In 12 patients (group 1) the jet
      appeared to emanate medially from the region of coaptation of the superior and
      inferior components of the anterior leaflet. In 9 patients (group 2) the jet
      emanated more laterally from the region toward the mural leaflet. The area ratios
      of the inferior leaflet were 32 +/- 4% in group 1 and 38 +/- 6% in group 2 (p =
      0.02). The area ratios of the mural leaflet were 28 +/- 5% in group 1 and 21 +/-
      5% in group 2 (p = 0.007). The superior leaflet area ratio was not different in
      groups 1 and 2, 40 +/- 9% and 41 +/- 6%, respectively. Three-dimensional
      echocardiography provides new insight into the anatomic determinants of MR
      following AVSD surgery.

PMID- 10080431
TI  - Usefulness of intraoperative transesophageal echocardiography in predicting the
      degree of mitral regurgitation secondary to atrioventricular defect in children.
AB  - The objectives of this study were to determine the validity of the grade of
      mitral regurgitation (MR) as imaged by intraoperative transesophageal
      echocardiography (TEE) in predicting the grade of MR at follow-up. Intraoperative
      TEE and corresponding follow-up transthoracic studies were retrospectively
      reviewed and the regurgitant jet area to left atrial area ratio was used to
      quantify the MR. Patient records were reviewed to identify factors contributing
      to the development of a certain grade of MR. Intraoperative TEE was useful in
      detecting severe MR that required further repair at the same time. However,
      discrepancy in the grade of MR at follow-up was noted in 47% of patients (21 of
      47) and unchanged grade of MR was found only in 53% of patients (26 of 47). Blood
      pressures were significantly lower and heart rates higher intraoperatively.
      Initial preoperative grade of MR and type of atrioventricular canal defect did
      not predispose for a particular grade of MR at follow-up. The grade of MR by
      intraoperative TEE does not predict the grade of MR at follow-up as imaged by
      transthoracic echocardiography.

PMID- 10080432
TI  - Endothelial reactivity and cardiac risk factors in older patients with peripheral
      arterial disease.
AB  - Peripheral arterial disease (PAD) is a major cause of morbidity and mortality.
      Endothelium-dependent vasoreactivity, which is advocated as a measure of vascular
      health, is impaired in persons with cardiac risk factors and coronary artery
      disease. Few studies have examined the degree of endothelial dysfunction in
      patients with PAD. Using high-resolution external vascular ultrasound, we
      measured brachial artery diameter and flow at rest, and in response to reactive
      hyperemia (flow-mediated dilation) in 50 older patients (age 69 +/- 1 year) with
      PAD (ankle-to-brachial artery index of 0.67 +/- 0.03), and 50 age-matched non-PAD
      patients. Coronary artery disease was more prevalent in PAD than in non-PAD
      patients (40% vs 4%, p <0.001). Systolic blood pressure (153 +/- 4 vs 141 +/- 3
      mm Hg, p <0.01), fasting glucose (129 +/- 6 vs 109 +/- 5 mg/dl, p <0.001), and
      pack-years smoked (54 +/- 7 vs 25 +/- 3, p <0.01) were higher in the PAD than in
      non-PAD patients. There were no differences in baseline brachial artery diameter,
      blood velocity, or flow between the 2 groups. However, the 1-minute postocclusion
      percent change in diameter (6.5 +/- 0.7% vs 9.8 +/- 0.7%, p <0.001) and the
      change in diameter (0.22 +/- 0.02 vs 0.33 +/- 0.02 mm, p <0.001) were lower in
      PAD than in non-PAD patients, suggesting impaired endothelium-dependent dilation.
      The postocclusion hyperemic velocity and blood flow were also lower in PAD than
      in non-PAD patients. In multiple regression analyses the low-density lipoprotein
      to-high-density lipoprotein cholesterol ratio, elevated fasting glucose, and high
      systolic blood pressure were independent predictors of percent change in brachial
      artery diameter (r2 = 0.37, p <0.001). Thus, older patients with PAD had impaired
      endothelial dependent vasodilation compared with controls that was associated
      with the presence of cardiac risk factors. The effect of cardiac risk factor
      intervention on endothelial function in patients with PAD remains to be
      determined.

PMID- 10080433
TI  - Prevalence and risk factors for abdominal aortic aneurysms in older adults with
      and without isolated systolic hypertension.
AB  - An association between abdominal aortic aneurysm (AAA) and atherosclerotic
      disease has been recognized and may be due to shared risk factors. A consistent
      relation between blood pressure and AAA has not been found. AAA was compared
      between those with and without isolated systolic hypertension (ISH) and
      prevalence of aortic atherosclerosis was evaluated. Abdominal aortic ultrasound
      was performed in 266 people, 143 with ISH and 123 age-similar controls. AAA was
      defined as an infrarenal aortic diameter of > or = 3.0 cm or an infrarenal-to
      suprarenal diameter ratio of > or = 1.2. The average age of participants was 73
      years. Overall prevalence of AAA was 9.4%, 11.9% in those with ISH and 6.5% among
      normotensives (p = 0.134). Multivariate analysis revealed male gender (p <0.001),
      higher low-density lipoprotein (p <0.001), higher pulse pressure (p = 0.032), and
      current smoking (p = 0.012) to be independent predictors of AAA. When evaluating
      aortic atherosclerosis, those with AAA had significantly larger diameters of the
      iliac arteries along with greater intimamedia thickness of the iliac arteries.
      Those with and without aneurysms had a similar prevalence of plaque (89% to 96%),
      but measured plaques tended to be larger among those with than without AAA (p
      <0.001). Progression of AAA after 1 year was observed in 8 participants, with a
      mean diameter change of 3.42 mm. AAA was found to be independently associated
      with pulse pressure but not with systolic blood pressure. Patients with AAA also
      had greater wall thickness and greater diameter of the iliac arteries, which are
      probably associated with the underlying disease process.

PMID- 10080434
TI  - Quantitative analysis of myocardial response to dobutamine by measurement of left
      ventricular wall motion using omnidirectional M-mode echocardiography.
AB  - Although dobutamine stress echocardiography is important for assessing cardiac
      ischemia and viability, analysis of wall motion is qualitatively performed. We
      quantitatively evaluated left ventricular wall motion using a newly developed
      omnidirectional M-mode echocardiography that can depict the M-mode at the site of
      region of interest on the 2-dimensional image in real time, and established its
      usefulness for analyzing the myocardial response to dobutamine infusion.
      Dobutamine stress echocardiography with omnidirectional M-mode was performed in
      57 patients with coronary lesions. In 38 of these patients, exercise stress
      single-photon emission computed tomographic thallium scintigraphy (Tl-201 SPECT)
      was performed. Endocardial excursion of 103 regions was measured from
      omnidirectional M-mode at baseline, low-dose (6 microg/kg/min), and at peak dose
      (30 microg/kg/min) dobutamine. A decrease and increase in wall excursion was
      scored (from -3 to 3) for a changes of every 2 mm, and a quantitative wall motion
      score (QWMS) was calculated as a summation of the scores from baseline to low
      dose and from low to peak doses. Quantitative coronary stenosis score (QCSS) was
      calculated as a summation of stenotic and collateral scores. The stenosis scores
      were graded as: 1 = 0% to 50%, 2 = 50% to 75%, 3 = 75% to 90%, 4 = 90% to 95%, 5
      = 95% to 100%; collateral scores were graded as: -1 = poor collateral, -2 = good
      collateral. Based on the QWMS at each dose of dobutamine, the serial changes in
      wall motion were divided into 4 groups: augmented, biphasic, no change, and
      worsening. The QCSS was clearly different among these groups. QWMS was
      significantly correlated with QCSS (r = 0.657, p <0.001). The incidence of
      redistribution in Tl-201 SPECT was high in the region with low score of QWMS. In
      conclusion, omnidirectional M-mode is useful for quantitatively determining the
      grade of cardiac ischemia by assessing the serial change of ventricular wall
      motion during dobutamine infusion.

PMID- 10080435
TI  - The lack of augmentation by aspirin of inhibition of platelet reactivity by
      ticlopidine.
AB  - A decreased threshold for platelet activation apparently contributes to the risk
      of cardiovascular events, such as acute myocardial infarction. To evaluate the
      impact of specific agents, we characterized platelet reactivity in 9 healthy
      subjects before and after 5 days of ingestion of 4 commonly prescribed regimens,
      81 mg of aspirin daily, 325 mg of aspirin daily, ticlopidine 250 mg twice daily,
      and ticlopidine plus 325 mg of aspirin daily. Platelet reactivity was assessed
      with (1) aggregometry induced by 4 microM adenosine diphosphate (ADP) and
      collagen (0.19 mg/ml) and performed in platelet-rich plasma; and (2) flow
      cytometric determination of ADP-induced (0.2, 0.8, and 1.5 microM) P-selectin
      expression in whole blood. Because anticoagulants alter platelet reactivity,
      results were obtained with 3 anticoagulants, citrate, enoxaparin, or corn trypsin
      inhibitor (CTI, a specific inhibitor of factor XIIa without effect on other
      coagulation factors). Ingestion of aspirin did not alter platelet activation as
      assessed with flow cytometry. Inhibition of the second phase of aggregation was
      seen with ADP-induced aggregation in platelet-rich plasma anticoagulated with
      citrate but not enoxaparin or CTI. Ingestion of ticlopidine led to inhibition of
      ADP-induced aggregation and P-selectin expression. Inhibition of platelet
      reactivity after the combination of aspirin and ticlopidine did not differ from
      ticlopidine alone. Marked interindividual variability in platelet reactivity was
      seen after ingestion of ticlopidine. The results indicate that assessment of
      effects of specific pharmacologic regimens with accurate and readily available
      assays of platelet reactivity may facilitate effective prophylaxis and treatment
      of high-risk subjects with antiplatelet regimens designed to optimally diminish
      platelet reactivity.

PMID- 10080436
TI  - Comparison of frequencies of atrial fibrillation after coronary artery bypass
      grafting with and without the use of cardiopulmonary bypass.
AB  - This study compared the incidence of postoperative atrial fibrillation in a group
      of 34 patients undergoing coronary artery bypass graft surgery without the use of
      cardiopulmonary bypass and cardioplegia with a control group of 747 patients
      undergoing coronary artery bypass graft surgery using cardiopulmonary bypass and
      standard cardioplegia. A trend toward a lower incidence of postoperative atrial
      fibrillation was found in the group that underwent coronary artery bypass graft
      surgery without the use of cardiopulmonary bypass (n = 0.06).

PMID- 10080437
TI  - Sequential changes in heart rate variability after coronary artery bypass
      grafting.
AB  - Heart rate variability (HRV) decreased soon after coronary artery bypass grafting
      and returned to the preoperative level within 2 months; however, HRV did not
      exceed the preoperative level, even 6 months after coronary artery bypass
      grafting. Although myocardial ischemia can be improved by coronary artery bypass
      grafting, HRV did not benefit from coronary artery bypass grafting within 6
      months.

PMID- 10080438
TI  - Mechanisms, management, and outcome of failure of delivery of coronary stents.
AB  - In a single-center experience, initial failure of attempted stent delivery was
      relatively infrequent (2.7%) but was associated with increased need for urgent
      coronary bypass surgery. Delivery failure was more likely with coiled stents and
      dislodgment from the delivery balloon was more likely with hand-mounted or
      radiolucent stents.

PMID- 10080439
TI  - Usefulness of measurement of plasma atrial natriuretic peptide levels in exercise
      testing of patients with coronary heart disease.
AB  - Atrial natriuretic peptide secretion on exercise testing may be exaggerated by
      left ventricular dysfunction due to multivessel coronary disease rather than by
      scintigraphically detectable myocardial ischemia. The measurement of plasma
      atrial natriuretic peptide levels during exercise test may provide additional
      information regarding the severity of coronary heart disease.

PMID- 10080440
TI  - Radiofrequency ablation of "class IC atrial flutter" in patients with resistant
      atrial fibrillation.
AB  - In some patients with atrial fibrillation, atrial flutter develops after
      administration of class IC antiarrhythmic drugs, the so-called class IC atrial
      flutter. Radiofrequency ablation of the right atrial isthmus results in clinical
      improvement in 85% of patients and provides an alternative management strategy
      for a subset of patients with therapy-resistant atrial fibrillation.

PMID- 10080441
TI  - Acute treatment of atrial fibrillation: spontaneous conversion rates and cost of
      care.
AB  - Acute treatment of atrial fibrillation is costly although spontaneous conversion
      rates are high. We reviewed 114 patients admitted to our inpatient service via
      the emergency department with a principal diagnosis of atrial fibrillation and
      found the spontaneous conversion rate was 50% in 48 hours, the average length of
      stay was 3.9 +/- 5.2 days, and the average cost was $6,692 +/- $4,928.

PMID- 10080442
TI  - Interaction of a commercial heart rate monitor with implanted pacemakers.
AB  - Dry-electrode heart rate monitors allow display of heart rate by transmitting a
      signal to the receiving device, which typically is on the wrist or exercise
      machine, but due to the potential for electromagnetic interference, their use has
      been contraindicated in patients with pacemakers. In 12 patients, we found no
      adverse effect on pacemaker function; in addition, the monitors generally were
      accurate in measuring heart rate during pacing.

PMID- 10080443
TI  - Evaluation of extent of shortening versus velocity of shortening at the
      endocardium and midwall in hypertensive heart disease.
AB  - To assess the incremental value of velocity of shortening velocity parameters
      compared with simpler, more widely used, extent of shortening parameters in
      compensated left ventricular hypertrophy, we studied 52 patients with left
      ventricular hypertrophy and 63 age-matched controls. Velocity parameters did not
      provide incremental information beyond that obtained by extent of shortening
      parameters.

PMID- 10080444
TI  - Nasal oxygen effects on arterial carbon dioxide pressure and heart rate in
      chronic heart failure.
AB  - Nasal oxygen applied by nasal prongs reduced tidal volume and increased carbon
      dioxide partial pressure in patients with chronic heart failure but not in
      comparable controls, whereas the patients showed a more pronounced decrease in
      heart rate with oxygen. These findings indicate that nasal oxygen has distinct
      effects on ventilation and heart rate in chronic heart failure.

PMID- 10080445
TI  - Assessment of restrictive cardiomyopathy of amyloid or idiopathic etiology by
      magnetic resonance imaging.
AB  - This study was designed to assess the role of magnetic resonance imaging in the
      differential diagnosis of amyloid and idiopathic etiology of cardiomyopathy. This
      technique demonstrated the capability to differentiate the 2 forms, providing
      high-resolution evaluation of the myocardial wall and detecting the infiltrative
      pathology by tissue characterization.

PMID- 10080446
TI  - Truncus arteriosus with anomalous pulmonary venous connection.
AB  - The anatomic, diagnostic, and management findings of 6 patients with truncus
      arteriosus and anomalous pulmonary venous connections are described. Additional
      risk factors indicative of poor prognosis were found in 3 of 4 patients with
      truncus arteriosus and totally anomalous pulmonary venous connection and in 1
      patient with partially anomalous pulmonary venous connection.

PMID- 10080447
TI  - Recovery of regional right ventricular function after thrombolysis for pulmonary
      embolism.
AB  - Abnormalities in right ventricular regional and global function can occur in the
      setting of acute pulmonary embolism. Treatment of acute pulmonary embolism with
      thrombolysis is associated with significant improvement in regional and global
      right ventricular function.

PMID- 10080448
TI  - Effect of verapamil on QT interval dynamicity.
AB  - Using measurements of QT/RR slopes with a computerized Holter system, QT interval
      dynamicity was evaluated in 19 patients with normal structural heart before and 2
      months after oral treatment with verapamil prescribed for paroxysmal
      atrioventricular nodal reentrant tachycardia. Verapamil significantly shortened
      QT at low heart rates, mainly in the diurnal period, and this characteristic may
      explain, in part, the previously reported protective effect of verapamil against
      torsades de pointes.

PMID- 10080449
TI  - Coil embolization of coronary supply to a cardiac metastasis.
AB  - Coil embolization of tumor-related coronary arteries was successful in
      interrupting coronary supply to a cardiac metastasis from uterine leiomyosarcoma.
      In patients with cardiac metastases of highly malignant tumors this may be a
      palliative therapeutic approach.

PMID- 10080450
TI  - Long-term follow-up of a true contractile left ventricular diverticulum.
AB  - The natural history of contractile left ventricular diverticulum in the adult is
      not known. Serial left ventricular angiography in an adult revealed that a left
      ventricular diverticulum did not increase in size over a 13-year period,
      suggesting that the clinical course may be benign.

PMID- 10080451
TI  - Ventricular fibrillation due to long QT syndrome probably caused by clindamycin.
AB  - Prolongation of QT time interval may be provoked by a limited number of drugs,
      especially macrolide antibiotics. We describe a case of QT time interval
      prolongation induced by clindamycin with subsequent repeated ventricular
      fibrillation and resuscitation; there is no previous report in the literature of
      QT time prolongation caused by lincosamides.

PMID- 10080452
TI  - Shifting from decreasing risk to actually preventing and arresting
      atherosclerosis.

PMID- 10080453
TI  - Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients:
      why is someone still using the phase I diet for patients at risk for
      atherosclerosis?

PMID- 10080454
TI  - Isomerism of the atrial appendages.

PMID- 10080455
TI  - The Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET) and
      combination therapies.

PMID- 10080456
TI  - 50th anniversary historical article. Hypertension.

PMID- 10080457
TI  - Effect of angiotensin converting enzyme inhibition on sudden cardiac death in
      patients following acute myocardial infarction. A meta-analysis of randomized
      clinical trials.
AB  - Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk
      of sudden cardiac death (SCD) following myocardial infarction (MI). BACKGROUND:
      Trials in post-MI patients have shown that ACE inhibitor therapy reduces
      mortality. However, the effect on SCD as a mechanism has not been clarified.
      METHODS: Trials of ACE inhibitor therapy following MI reported between January,
      1978 and August, 1997 were identified. Studies were included if they met the
      following criteria: 1) randomized comparison of ACE inhibitor to placebo within
      14 days of MI; 2) study duration/blinded follow-up of > or =6 weeks; 3) the
      number of deaths and modes of death were reported or could be obtained from the
      investigators. RESULTS: We identified 374 candidate articles, of which 15 met the
      inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died.
      Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant
      reduction in SCD risk or a trend towards this was observed in all of the larger
      (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant
      reductions in risk of death (random effects odds ratio [OR] = 0.83; 95%
      confidence interval [CI] 0.71-0.97), cardiovascular death (OR = 0.82; 95% CI 0.69
      0.97) and SCD (OR = 0.80; 95% CI 0.70-0.92). CONCLUSIONS: This analysis is
      consistent with prior reports showing that ACE inhibitors decrease the risk of
      death following a recent MI by reducing cardiovascular mortality. Moreover, this
      analysis suggests that a reduction in SCD risk with ACE inhibitors is an
      important component of this survival benefit.

PMID- 10080458
TI  - Primary angioplasty versus systemic thrombolysis in anterior myocardial
      infarction.
AB  - OBJECTIVES: This study compares the efficacy of primary angioplasty and systemic
      thrombolysis with t-PA in reducing the in-hospital mortality of patients with
      anterior AMI. BACKGROUND: Controversy still exists about the relative benefit of
      primary angioplasty over thrombolysis as treatment for AMI. METHODS: Two-hundred
      and twenty patients with anterior AMI were randomly assigned in our institution
      to primary angioplasty (109 patients) or systemic thrombolysis with accelerated t
      PA (111 patients) within the first five hours from the onset of symptoms.
      RESULTS: Baseline characteristics were similar in both groups. Primary
      angioplasty was independently associated with a lower in-hospital mortality (2.8%
      vs. 10.8%, p = 0.02, adjusted odds ratio 0.23, 95% confidence interval 0.06 to
      0.85). During hospitalization, patients treated by angioplasty had a lower
      frequency of postinfarction angina or positive stress test (11.9% vs. 25.2%, p =
      0.01) and less frequently underwent percutaneous or surgical revascularization
      after the initial treatment (22.0% vs. 47.7%, p < 0.001) than did patients
      treated by t-PA. At six month follow-up, patients treated by angioplasty had a
      lower cumulative rate of death (4.6% vs. 11.7%, p = 0.05) and revascularization
      (31.2% vs. 55.9%, p < 0.001) than those treated by t-PA. CONCLUSIONS: In centers
      with an experienced and readily available interventional team, primary
      angioplasty is superior to t-PA for the treatment of anterior AMI.

PMID- 10080459
TI  - Relationship of glucose and insulin levels to the risk of myocardial infarction:
      a case-control study.
AB  - OBJECTIVE: To assess the relationship between dysglycemia and myocardial
      infarction in nondiabetic individuals. BACKGROUND: Nondiabetic hyperglycemia may
      be an important cardiac risk factor. The relationship between myocardial
      infarction and glucose, insulin, abdominal obesity, lipids and hypertension was
      therefore studied in South Asians-a group at high risk for coronary heart disease
      and diabetes. METHODS: Demographics, waist/hip ratio, fasting blood glucose
      (FBG), insulin, lipids and glucose tolerance were measured in 300 consecutive
      patients with a first myocardial infarction and 300 matched controls. RESULTS:
      Cases were more likely to have diabetes (OR 5.49; 95% CI 3.34, 9.01), impaired
      glucose tolerance (OR 4.08; 95% CI 2.31, 7.20) or impaired fasting glucose (OR
      3.22; 95% CI 1.51, 6.85) than controls. Cases were 3.4 (95% CI 1.9, 5.8) and 6.0
      (95% CI 3.3, 10.9) times more likely to have an FBG in the third and fourth
      quartile (5.2-6.3 and >6.3 mmol/1); after removing subjects with diabetes,
      impaired glucose tolerance and impaired fasting glucose, cases were 2.7 times
      (95% CI 1.5-4.8) more likely to have an FBG >5.2 mmol/l. A fasting glucose of 4.9
      mmol/l best distinguished cases from controls (OR 3.42; 95% CI 2.42, 4.83).
      Glucose, abdominal obesity, lipids, hypertension and smoking were independent
      multivariate risk factors for myocardial infarction. In subjects without glucose
      intolerance, a 1.2 mmol/l (21 mg/dl) increase in postprandial glucose was
      independently associated with an increase in the odds of a myocardial infarction
      of 1.58 (95% CI 1.18, 2.12). CONCLUSIONS: A moderately elevated glucose level is
      a continuous risk factor for MI in nondiabetic South Asians with either normal or
      impaired glucose tolerance.

PMID- 10080460
TI  - Reciprocal ST-segment depression associated with exercise-induced ST-segment
      elevation indicates residual viability after myocardial infarction.
AB  - OBJECTIVES: We evaluated the clinical significance of reciprocal ST-segment
      depression associated with exercise-induced ST-segment elevation for detecting
      residual viability within the infarcted area. BACKGROUND: Although the relation
      between residual viability and exercise-induced ST-segment elevation has been
      described, there are no reports focusing on the relation between myocardial
      viability and reciprocal ST-segment depression associated with exercise-induced
      ST-segment elevation. METHODS: We evaluated regional blood flow and glucose
      utilization using N-13 ammonia (NH3) and F-18 fluorodeoxyglucose (FDG) positron
      emission tomography (PET) in 30 patients with a previous Q-wave myocardial
      infarction (anterior in 15, inferior in 15). All subjects had single-vessel
      disease and had exercise-induced ST-segment elevations (> or =1 mm) in
      electrocardiographic leads. RESULTS: Reciprocal ST-segment depression (> or =1
      mm) was present in 16 patients (Group A; anterior in 6, inferior in 10) but not
      in the remaining 14 patients (Group B). The degree of exercise-induced ST-segment
      elevation (1.8+/-0.2 vs. 2.0+/-0.2 mm) and the time from the onset of infarction
      to the study (75+/-49 vs. 74+/-52 days) did not differ between groups. There were
      no significant differences between groups in the severity of left ventricular
      dysfunction and the residual luminal narrowing in the infarct-related artery
      (45+/-21 vs. 48+/-25%). The presence and site of infarction were confirmed by NH3
      PET in all patients. FDG-PET demonstrated residual tissue viability within
      infarct-related area in all patients in Group A and in 3 (21%) of 14 patients in
      Group B (p < 0.01). The sensitivity, specificity and accuracy of reciprocal ST
      segment depression associated with exercise-induced ST-segment elevation for
      detecting residual viability were 84%, 100% and 90%, respectively. CONCLUSIONS:
      The occurrence of reciprocal ST-segment depression associated with exercise
      induced ST segment elevation in patients with a previous Q-wave infarction who
      had single-vessel disease indicates residual tissue viability within the infarct
      related area.

PMID- 10080461
TI  - Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis
      in acute myocardial infarction--a pilot study: biochemical markers in acute
      coronary syndromes (BIOMACS II).
AB  - OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial
      evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients
      with acute myocardial infarction regarding early reperfusion, recurrent ischemia
      and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given
      subcutaneously twice daily without monitoring, might be an attractive alternative
      to conventional intravenous heparin in the treatment of acute myocardial
      infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just
      before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with
      continuous vector-ECG was done to obtain signs of early reperfusion and later
      ischemic episodes. Blood samples for myoglobin were obtained at start and after
      90 min to evaluate signs of reperfusion. Coronary angiography was performed after
      20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin
      added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in
      infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin
      had no effects on noninvasive signs of early reperfusion. In patients with signs
      of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74%
      versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11).
      Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin
      group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an
      adjuvant to streptokinase and aspirin, there were tendencies for less ECG
      monitoring evidence of recurrent ischemia and better patency at 24 h, warranting
      further study.

PMID- 10080462
TI  - Platelet activation in patients after an acute coronary syndrome: results from
      the TIMI-12 trial. Thrombolysis in Myocardial Infarction.
AB  - This study was designed to determine the magnitude and time course of platelet
      activation during therapy of acute coronary syndromes with an oral platelet
      antagonist. BACKGROUND: Platelet activation and aggregation are central to the
      pathogenesis of the acute coronary syndromes (ACS). However, few data are
      available on levels of platelet activation over time in patients with ACS,
      especially in the setting of chronic glycoprotein (GP) IIb/IIIa inhibition.
      METHODS: The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase
      II, double-blind trial evaluating the effects of sibrafiban, an oral, selective
      antagonist of the platelet glycoprotein IIb/IIIa receptor in patients stabilized
      after an ACS. A subset of 90 of the 329 patients in the study had measurement of
      platelet activation as assessed by the expression of platelet associated P
      Selectin on days 0, 7 and 28. Platelet activation was measured in blood samples
      that were fixed either immediately (spontaneous activation) or after 5 minute
      incubation with 0, 1 microM or 5 microM ADP in order to assess platelet
      responsiveness to very low or moderate stimulation. RESULTS: At baseline there
      was a significant elevation of spontaneous platelet activation as compared to
      samples obtained from normal donors or from patients who did not have acute
      coronary syndromes (ACS patients 27.6+/-18.7%, Normal controls 8.5+/-4.4%,
      Patient controls 10.9+/-7.1%, p < 0.005 for both). In addition, there was a
      significant decrease in the levels of platelet activation with time during the 28
      days of treatment with sibrafiban. Nevertheless, even on day 28, the TIMI-12
      patients continued to show elevated platelet activation in comparison to the
      control groups (p < 0.05 for both). CONCLUSIONS: These results suggest that
      platelets remain activated long after clinical stabilization post ACS. Although
      platelet activation decreased after one month of oral GPIIb/IIIa inhibition,
      levels remained higher than normal, suggesting the need for long-term
      antiplatelet therapy following ACS.

PMID- 10080463
TI  - Long-term outcome after primary angioplasty: report from the primary angioplasty
      in myocardial infarction (PAMI-I) trial.
AB  - OBJECTIVES: This study sought to compare the two-year outcome after primary
      percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial
      infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without
      antecedent thrombolytic therapy, has been shown to be an effective reperfusion
      modality for patients suffering an acute myocardial infarction. This report
      reviews the two-year clinical outcome of patients randomized in the Primary
      Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395
      patients who presented within 12 h of the onset of myocardial infarction were
      randomized to undergo primary angioplasty (195 patients) or to receive tissue
      type plasminogen activator (t-PA) (200 patients) followed by conservative care.
      Patients were followed by physician visits, phone call, letter and review of
      hospital records for any hospital admission at one month, six months, one year
      and two years. RESULTS: At two years, patients undergoing primary angioplasty had
      less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention
      rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission
      rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or
      reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034.
      Multivariate analysis found angioplasty to be independently predictive of a
      reduction in death, reinfarction or target vessel revascularization (p = 0.0001).
      CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced
      operators is maintained over a two-year follow-up period with improved infarct
      free survival and reduced rate of reintervention.

PMID- 10080464
TI  - The relationship between periprocedural myocardial infarction and subsequent
      target vessel revascularization following percutaneous coronary
      revascularization: insights from the EPIC trial. Evaluation of IIb/IIIa platelet
      receptor antagonist 7E3 in Preventing Ischemic Complications.
AB  - OBJECTIVES: We sought to determine whether periprocedural myocardial infarction
      complicating percutaneous coronary revascularization is associated with
      subsequent clinical restenosis, as judged by the need for target vessel
      revascularization. BACKGROUND: Although myocardial enzyme elevation following
      angioplasty is associated with increased late mortality, its effect on subsequent
      clinical restenosis, as assessed by the need for late target vessel
      revascularization (TVR), is unknown. METHODS: Serial myocardial enzyme
      determinations were performed on 2,099 patients who underwent angioplasty or
      atherectomy in the Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in
      Preventing Ischemic Complications (EPIC) trial. Thirty-day survivors were
      prospectively followed for three years for adverse clinical events including
      death and need for TVR. RESULTS: Within the study population, periprocedural
      creatine kinase (CK) elevation was a predictor of late mortality. Among patients
      with elevated CK, however, a paradoxical decrease in the need for late TVR was
      present. This relationship became progressively more profound as the magnitude of
      CK release increased. Late TVR occurred in 29.8% of patients with no CK
      elevation, 24.8% with CK elevation to >3 times normal, and 16.9% with >10 times
      elevation (hazard ratio 0.51, 95% CI 0.29, 0.91). CONCLUSIONS: In the EPIC study,
      patients with periprocedural MI were less likely to develop clinical restenosis
      as measured by the need for TVR. Mechanistically, although it is unlikely that CK
      elevation prevents vascular renarrowing per se, myocardial necrosis impairs the
      clinical manifestation of restenosis, thereby reducing the need for ischemia
      driven TVR. This novel finding 1) highlights the potential discordance between
      angiographic and clinical measures of restenosis, and 2) has implications for
      clinical trials, as therapies that reduce periprocedural MI may be associated
      with a perceived excess of restenosis when measured by the need for TVR.

PMID- 10080465
TI  - Intravenous nicorandil can preserve microvascular integrity and myocardial
      viability in patients with reperfused anterior wall myocardial infarction.
AB  - OBJECTIVES: We assessed whether the intravenous administration of nicorandil, an
      adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial
      effect on microvascular function and functional and clinical outcomes in patients
      with acute myocardial infarction (AMI). BACKGROUND: Experimental studies
      documented that ATP-sensitive K+ channel opener exerts cardioprotection after
      prolonged ischemia. METHODS: We randomly divided 81 patients with a first
      anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41).
      All patients received successful coronary angioplasty within 12 h after the
      symptom onset and underwent myocardial contrast echcardiography (MCE) with the
      intracoronary injection of sonicated microbubbles. In the nicorandil group, we
      injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by
      oral nicorandil (15 mg/day). RESULTS: The improvement in regional left
      ventricular function, wall motion score and regional wall motion was
      significantly better in the nicorandil group then in the control group.
      Intractable congestive heart failure, malignant ventricular arrhythmia and
      pericardial effusion were more frequently found in the control group than in the
      nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05,
      respectively). The frequency of sizable MCE no reflow phenomenon was
      significantly lower in the nicorandil group than in the control group (15% vs.
      33%, p < 0.05). CONCLUSIONS: Intravenous nicorandil in conjunction with coronary
      angioplasty is associated with better functional and clinical outcomes compared
      to angioplasty alone in patients with an anterior AMI. Myocardial contrast
      echocardiography findings imply that an improvement in microvascular function
      with nicorandil may be attributable to this better outcome.

PMID- 10080466
TI  - The economic consequences of available diagnostic and prognostic strategies for
      the evaluation of stable angina patients: an observational assessment of the
      value of precatheterization ischemia. Economics of Noninvasive Diagnosis (END)
      Multicenter Study Group.
AB  - OBJECTIVES: The study aim was to determine observational differences in costs of
      care by the coronary disease diagnostic test modality. BACKGROUND: A number of
      diagnostic strategies are available with few data to compare the cost
      implications of the initial test choice. METHODS: We prospectively enrolled
      11,372 consecutive stable angina patients who were referred for stress myocardial
      perfusion tomography or cardiac catheterization. Stress imaging patients were
      matched by their pretest clinical risk of coronary disease to a series of
      patients referred to cardiac catheterization. Composite 3-year costs of care were
      compared for two patients management strategies: 1) direct cardiac
      catheterization (aggressive) and 2) initial stress myocardial perfusion
      tomography and selective catheterization of high risk patients (conservative).
      Analysis of variance techniques were used to compare costs, adjusting for
      treatment propensity and pretest risk. RESULTS: Observational comparisons of
      aggressive as compared with conservative testing strategies reveal that costs of
      care were higher for direct cardiac catheterization in all clinical risk subsets
      (range: $2,878 to $4,579), as compared with stress myocardial perfusion imaging
      plus selective catheterization (range: $2,387 to $3,010, p < 0.0001). Coronary
      revascularization rates were higher for low, intermediate and high risk direct
      catheterization patients as compared with the initial stress perfusion imaging
      cohort (13% to 50%, p < 0.0001); cardiac death or myocardial infarction rates
      were similar (p > 0.20). CONCLUSIONS: Observational assessments reveal that
      stable chest pain patients who undergo a more aggressive diagnostic strategy have
      higher diagnostic costs and greater rates of intervention and follow-up costs.
      Cost differences may reflect a diminished necessity for resource consumption for
      patients with normal test results.

PMID- 10080467
TI  - Quantification of collateral flow in humans: a comparison of angiographic,
      electrocardiographic and hemodynamic variables.
AB  - OBJECTIVES: Evaluation of collateral vascular circulation according to
      hemodynamic variables and its relation to myocardial ischemia. BACKGROUND: There
      is limited information regarding the hemodynamic quantification of recruitable
      collateral vessels. METHODS: Angiography of the donor coronary artery was
      performed before and during balloon coronary occlusion in 63 patients with one
      vessel disease. Patients were divided into groups of those with an absence of
      collateral vessels (group 1, n = 10), those with recruitable collateral vessels
      (group 2, n = 23) and those with spontaneously visible collateral vessels (group
      3, n = 30). During balloon inflation the coronary wedge/aortic pressure ratio
      (Pw/Pao) was determined as were collateral blood flow velocity variables, using a
      0.014" Doppler guide wire. Myocardial ischemia was defined as > or =0.1 mV ST
      shift on a 12 lead electrocardiogram at 1 min coronary occlusion. RESULTS:
      Myocardial ischemia was present in all patients of group 1, in 14 patients of
      group 2 and in 3 patients of group 3. Recruitable collateral flow without
      ischemia showed similar hemodynamic values as in group 3 while these values were
      similar to group 1 in regard to the presence of recruitable collateral vessels
      showing ischemia. Logistic regression analysis revealed both Pw/Pao and Vi(col)
      as independent predictors for the function of collateral vessels. CONCLUSIONS:
      Hemodynamic variables of collateral vascular circulation are better markers of
      the functional significance of collateral vessels than is coronary angiography.
      The total collateral blood flow velocity integral and coronary wedge/aortic
      pressure ratio are good and independent predictors of the function of collateral
      vessels producing complementary information.

PMID- 10080468
TI  - 13N-ammonia myocardial blood flow and uptake: relation to functional outcome of
      asynergic regions after revascularization.
AB  - OBJECTIVES: In this study we determined whether 13N-ammonia uptake measured late
      after injection provides additional insight into myocardial viability beyond its
      value as a myocardial blood flow tracer. BACKGROUND: Myocardial accumulation of
      13N-ammonia is dependent on both regional blood flow and metabolic trapping.
      METHODS: Twenty-six patients with chronic coronary artery disease and left
      ventricular dysfunction underwent prerevascularization 13N-ammonia and 18F
      deoxyglucose (FDG) positron emission tomography, and thallium single-photon
      emission computed tomography. Pre- and postrevascularization wall-motion
      abnormalities were assessed using gated cardiac magnetic resonance imaging or
      gated radionuclide angiography. RESULTS: Wall motion improved in 61 of 107 (57%)
      initially asynergic regions and remained abnormal in 46 after revascularization.
      Mean absolute myocardial blood flow was significantly higher in regions that
      improved compared to regions that did not improve after revascularization (0.63+/
      0.27 vs. 0.52+/-0.25 ml/min/g, p < 0.04). Similarly, the magnitude of late 13N
      ammonia uptake and FDG uptake was significantly higher in regions that improved
      (90+/-20% and 94+/-25%, respectively) compared to regions that did not improve
      after revascularization (67+/-24% and 71+/-25%, p < 0.001 for both,
      respectively). However, late 13N-ammonia uptake was a significantly better
      predictor of functional improvement after revascularization (area under the
      receiver operating characteristic [ROC] curve = 0.79) when compared to absolute
      blood flow (area under the ROC curve = 0.63, p < 0.05). In addition, there was a
      linear relationship between late 13N-ammonia uptake and FDG uptake (r = 0.68, p <
      0.001) as well as thallium uptake (r = 0.76, p < 0.001) in all asynergic regions.
      CONCLUSIONS: These data suggest that beyond its value as a perfusion tracer, late
      13N-ammonia uptake provides useful information regarding functional recovery
      after revascularization. The parallel relationship among 13N-ammonia, FDG, and
      thallium uptake supports the concept that uptake of 13N-ammonia as measured from
      the late images may provide important insight regarding cell membrane integrity
      and myocardial viability.

PMID- 10080469
TI  - Effects of pacing-induced and balloon coronary occlusion ischemia on left atrial
      function in patients with coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to compare left atrial (LA) function in 16
      patients with distal left anterior descending (LAD) and in 16 patients with
      proximal left circumflex (LCx) coronary artery stenosis at rest and immediately
      after pacing-induced tachycardia (LAD-pacing [P] and LCx-P) or coronary occlusion
      (LAD-CO and LCx-CO). BACKGROUND: During left ventricular (LV) ischemia,
      compensatory augmentation of LA contraction enhances LV filling and performance.
      The left atrium is supplied predominantly by branches arising from the LCx.
      Therefore, we hypothesized that one mechanism for the loss of atrial contraction
      may be ischemic LA dysfunction. METHODS: Left ventricular and LA pressure-area
      relations were derived from simultaneous double-tip micromanometer pressure
      recordings and automatic boundary detection echocardiograms. RESULTS: Immediately
      after pacing or after coronary occlusion, LV end-diastolic pressure, LV
      relaxation, LA mean pressure and LV stiffness significantly increased in all
      patients. However, the area of the A loop of the LA pressure-area relation,
      representing the LA pump function, significantly decreased in groups LCx-P and
      LCx-CO (from 14+/-3 to 9+/-2, and from 16+/-4 to 9+/-2 mm Hg.cm2, respectively, p
      < 0.05), whereas it increased in groups LAD-P and LAD-CO (from 12+/-3 to 54+/-10,
      and from 16+/-3 to 49+/-8 mm Hg.cm2, respectively, p < 0.001). CONCLUSIONS: In
      patients with LAD stenosis, LV supply or demand ischemia is associated with
      enhanced LA pump function. However, in patients with proximal LCx stenosis who
      develop the same type and degree of ischemia, LA branches might have been
      affected, rendering the LA ischemic and unable to increase its booster pump
      function.

PMID- 10080470
TI  - Recovery of contractility of viable myocardium during inotropic stimulation is
      not dependent on an increase of myocardial blood flow in the absence of
      collateral filling.
AB  - OBJECTIVES: The purpose of this study was to determine whether contractile
      recovery induced by dobutamine in dysfunctioning viable myocardium supplied by
      nearly occluded vessels is related to an increase in blood flow in the absence of
      collaterals. BACKGROUND: Dobutamine is used to improve contractility in
      ventricular dysfunction during acute myocardial infarction. However, it is
      unclear whether a significant increase in regional blood flow may be involved in
      dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior
      infarction and > or =90% left anterior descending coronary artery stenosis
      underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and
      during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest
      echocardiography and scintigraphy were repeated >1 month after revascularization.
      Nine patients had collaterals to the infarcted territory (group A), and 11 did
      not (group B). RESULTS: Baseline wall motion score was similar in both groups
      (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at
      dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p <
      0.0001). Wall motion score improved significantly (p < 0.001) in group A both at
      dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well
      as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi
      uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas
      at dobutamine and postrevascularization studies a significant change (F[2,30] =
      65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p <
      0.0001) were present. Tracer uptake increased significantly in group A both at
      dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/
      8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake
      after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization
      (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by
      low dose dobutamine infusion in dysfunctional viable myocardium supplied by
      nearly occluded vessels occurs even in the absence of a significant increase in
      blood flow.

PMID- 10080471
TI  - Contractile reserve and coronary blood flow reserve in collateral-dependent
      myocardium.

PMID- 10080472
TI  - Prognostic value of dobutamine stress echocardiography in predicting cardiac
      events in patients with known or suspected coronary artery disease.
AB  - OBJECTIVES: The study sought to determine the utility of dobutamine stress
      echocardiography (DSE) in predicting cardiac events in the year after testing.
      BACKGROUND: Increasingly, DSE has been applied to risk stratification of
      patients. METHODS: Medical records of 1,183 consecutive patients who underwent
      DSE were reviewed. The cardiac events that occurred during the 12 months after
      DSE were tabulated: myocardial infarction (MI), cardiac death, percutaneous
      transluminal coronary angioplasty (PTCA), and coronary artery bypass surgery
      (CABG). Patient exclusions included organ transplant receipt or evaluation,
      recent PTCA, noncardiac death, and lack of follow-up. A positive stress
      echocardiogram (SE) was defined as new or worsened wall-motion abnormalities
      (WMAs) consistent with ischemia during DSE. Classification and regression tree
      (CART) analysis identified variables that best predicted future cardiac events.
      RESULTS: The average age was 68+/-12 years, with 338 women and 220 men. The
      overall cardiac event rate was 34% if SE was positive, and 10% if it was
      negative. The event rates for MI and death were 10% and 8%, respectively, if SE
      was positive, and 3% and 3%, respectively, if SE was negative. If an ischemic
      electrocardiogram (ECG) and a positive SE were present, the overall event rate
      was 42%, versus a 7% rate when ECG and SE were negative for ischemia. Rest WMA
      was the most useful variable in predicting future cardiac events using CART: 25%
      of patients with and 6% without a rest WMA had an event. Other important
      variables were a dobutamine EF <52.5%, a positive SE, an ischemic ECG response,
      history of hypertension and age. CONCLUSIONS: A positive SE provides useful
      prognostic information that is enhanced by also considering rest-wall motion,
      stress ECG response, and dobutamine EF.

PMID- 10080473
TI  - Integrated evaluation of relation between coronary lesion features and stress
      echocardiography results: the importance of coronary lesion morphology.
AB  - OBJECTIVES: The aim of this study was to analyze, in the same group of patients,
      the relationship between multiple variables of coronary lesion and results of
      exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND:
      Integrated evaluation of the relation between stress echocardiography results and
      angiographic variables should include not only the assessment of stenosis
      severity but also evaluation of other quantitative and qualitative features of
      coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30
      female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill
      protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10
      min) stress echocardiography tests were performed. Stress echocardiography test
      was considered positive for myocardial ischemia when a new wall motion
      abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis
      to complete obstruction of the vessel was present in 153 patients, and 15
      patients had normal coronary arteries. The observed angiographic variables
      included particular coronary vessel, stenosis location, the presence of
      collaterals, plaque morphology according to Ambrose classification, percent
      diameter stenosis and obstruction diameter as assessed by quantitative coronary
      arteriography. RESULTS: Covariates significantly associated with the results of
      physical and pharmacological stress tests included for all three stress
      modalities presence of collateral circulation, percent diameter stenosis and
      obstruction diameter, as well as lesion morphology (p < 0.05 for all, except
      collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic
      regression analysis, the strongest predictor of the outcome of exercise
      echocardiography test was only percent diameter stenosis (p = 0.0002). However,
      both dobutamine and particularly dipyridamole stress echocardiography results
      were associated not only with stenosis severity - percent diameter stenosis
      (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more
      strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p =
      0.0009). As all of stress echocardiography results were significantly associated
      with percent diameter stenosis, the best angiographic cutoff in relation to the
      results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and
      dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of
      angiographic variables have shown that the results of dobutamine and dipyridamole
      stress echocardiography are not only influenced by stenosis severity but also,
      and even more importantly, by plaque morphology. The results of exercise stress
      echocardiography, although separately influenced by plaque morphology, are
      predominantly influenced by stenosis severity, due to a stronger exercise
      capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

PMID- 10080474
TI  - Associations between a polymorphism in the gene encoding glycoprotein IIIa and
      myocardial infarction or coronary artery disease.
AB  - OBJECTIVES: The purpose of this study was to determine whether a common variant
      (PIA2) of the membrane glycoprotein (GP) IIIa gene is associated with myocardial
      infarction (MI) or coronary artery disease (CAD). BACKGROUND: Platelet GP
      IIb/IIIa is believed to play a central role in MI, binding fibrinogen, cross
      linking platelets and initiating thrombus formation. Genetically determined
      differences in binding properties of GP IIb/IIIa might result in changes in
      platelet activation or aggregation and affect the risk of MI or CAD. METHODS: To
      determine associations (odds ratios [OR] > or =1.5 to 2.0) of genotype with MI or
      CAD, blood was drawn from 791 patients (pt) undergoing angiography. A 266 base
      pair fragment of the GP IIIa gene was amplified by the polymerase chain reaction
      and digested with the MspI restriction enzyme. Genotypes were identified after
      electrophoresis of digestion products in 1.5% agarose gel. RESULTS: Of the 791
      pt, 225 had acute (n = 143) or previous MI, and 276 did not have MI or unstable
      angina. The PI(A2) allele was carried by 33.8% of MI pt versus 26.9% of no-MI
      control subjects, OR = 1.39 (95% CI, 0.95 to 2.04, p = 0.09). Angiographically,
      549 pt had severe (>60% coronary stenosis) CAD, and 170 had normal coronary
      arteries (<10% stenosis). The PI(A2) allele was found in 31.0% of CAD pt versus
      28.2% of no-CAD control subjects, OR = 1.14 (CI, 0.78 to 1.67, p = 0.50). When
      adjusted for six standard risk factors, ORs were 1.47 (CI, 0.98 to 2.20, p =
      0.062) for MI and 1.20 (CI, 0.80 to 1.81, p = 0.38) for CAD. CONCLUSIONS: The
      PI(A2) variant of the gene encoding GP IIIa is modestly associated (OR
      approximately 1.5) with nonfatal MI but shows little if any association with CAD
      per se.

PMID- 10080475
TI  - Incidence, clinical and etiologic features, and outcomes of advanced chronic
      heart failure: the EPICAL Study. Epidemiologie de l'Insuffisance Cardiaque
      Avancee en Lorraine.
AB  - OBJECTIVES: Characterize the incidence, clinical and etiologic features and
      outcomes of advanced congestive heart failure. BACKGROUND: This condition is
      frequent, severe and costly, yet no population-based epidemiological data are
      available that take into account modern advances in diagnosis and therapy.
      METHODS: The EPICAL (Epidemiologie de l'Insuffisance Cardiaque Avancee en
      Lorraine) study was based on a comprehensive registration of patients with ACHF
      (defined as hospital admission for presence of NYHA class III or IV symptoms,
      radiological and/or clinical signs of pulmonary congestion and/or signs of
      peripheral edema, left ventricular ejection fraction <30% or a cardiothoracic
      ratio >60%) in patients aged 20-80 years during year 1994, in the community of
      the Lorraine region in France (n = 1,592,263). Average follow-up for readmission
      to hospital and mortality was 18 months (12-24 months). RESULTS: From 2,576
      registered patients, 499 were enrolled into the study among which, 358 were new
      presentations. This represents a crude incidence rate of 225 per million. 46.3%
      had a coronary heart disease. One-year mortality rate was 35.4% and the rate of
      mortality and/or readmission to hospital was 81%. Patients were admitted to
      hospital 2.05 times per year (64% of these for worsening heart failure), spending
      27.6 days per year in hospital. Twenty received a heart transplant (4%). On
      discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS:
      Mortality and hospitalization rate of advanced CHF remain very high despite
      recent therapeutic progress. Major therapeutic and managed-care research is
      required.

PMID- 10080476
TI  - Effect of intensive therapy for heart failure on the vasodilator response to
      exercise.
AB  - OBJECTIVES: The purpose of the study was to evaluate the lower extremity vascular
      responsiveness to metabolic stimuli in patients with heart failure and to
      determine whether these responses improve acutely after intensive medical
      therapy. BACKGROUND: Metabolic regulation of vascular tone is an important
      determinant of blood flow, and may be abnormal in heart failure. METHODS: The leg
      blood flow responses were measured in 11 patients with nonedematous class III-IV
      heart failure before and after inpatient medical therapy and in 10 normal
      subjects. Venous occlusion plethysmography was used to measure peak blood flow
      and total hyperemia in the calf after arterial occlusion and also after isotonic
      ankle exercise. Measurements were repeated following short-term inpatient
      treatment with vasodilators and diuretics administered to decrease right atrial
      pressure (18+/-2 to 7+/-1 mm Hg), pulmonary wedge pressure (32+/-3 to 15+/-2 mm
      Hg), and systemic vascular resistance (1581+/-200 to 938+/-63 dynes.s.cm(-5), all
      p < 0.02). RESULTS: Leg blood flow at rest, after exercise, and during reactive
      hyperemia was less in heart failure patients than in control subjects. Resting
      leg blood flow did not increase significantly after medical therapy, but peak
      flow after the high level of exercise increased by 59% (p = 0.009). Total
      hyperemic volume in the recovery period increased by 73% (p = 0.03). Similarly,
      the peak leg blood flow response to ischemia increased by 88% (p = 0.04), whereas
      hyperemic volume rose by 98% (p = 0.1). CONCLUSIONS: The calf blood flow
      responses to metabolic stimuli are blunted in patients with severe heart failure,
      and improve rapidly with intensive medical therapy.

PMID- 10080477
TI  - Functional status and quality of life in patients with heart failure undergoing
      coronary bypass surgery after assessment of myocardial viability.
AB  - OBJECTIVES: The aim of this study was to evaluate whether preoperative clinical
      and test data could be used to predict the effects of myocardial
      revascularization on functional status and quality of life in patients with heart
      failure and ischemic LV dysfunction. BACKGROUND: Revascularization of viable
      myocardial segments has been shown to improve regional and global LV function.
      The effects of revascularization on exercise capacity and quality of life (QOL)
      are not well defined. METHODS: Sixty three patients (51 men, age 66+/-9 years)
      with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart
      failure were studied before and after coronary artery bypass surgery. All
      patients underwent preoperative positron emission tomography (PET) using FDG and
      Rb-82 before and after dipyridamole stress; the extent of viable myocardium by
      PET was defined by the number of segments with metabolism-perfusion mismatch or
      ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients;
      viability was defined by augmentation at low dose or the development of new or
      worsening wall motion abnormalities. Functional class, exercise testing and a QOL
      score (Nottingham Health Profile) were obtained at baseline and follow-up.
      RESULTS: Patients had wall motion abnormalities in 83+/-18% of LV segments. A
      mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of
      viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18%
      of the LV by DbE. The difference between pre- and postoperative exercise capacity
      ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of
      improvement of exercise capacity correlated with the extent of viability by PET
      (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02,
      p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE
      (0.66). In a multiple linear regression, the extent of viability by PET and
      nitrate use were the only independent predictors of improvement of exercise
      capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated
      weakly with the change in exercise capacity (r = 0.25), extent of viable
      myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four
      components of the quality of life score (energy, pain, emotion and mobility
      status) significantly improved over follow-up, but no correlations could be
      identified between quality of life scores and the results of preoperative testing
      or changes in exercise capacity. CONCLUSIONS: In patients with LV dysfunction,
      improvement of exercise capacity correlates with the extent of viable myocardium.
      Quality of life improves in most patients undergoing revascularization. However,
      its measurement by this index does not correlate with changes in other parameters
      nor is it readily predictable.

PMID- 10080478
TI  - Cardiac metaiodobenzylguanidine uptake in patients with moderate chronic heart
      failure: relationship with peak oxygen uptake and prognosis.
AB  - OBJECTIVES: This prospective study was undertaken to correlate early and late
      metaiodobenzylguanidine (MIBG) cardiac uptake with cardiac hemodynamics and
      exercise capacity in patients with heart failure and to compare their prognostic
      values with that of peak oxygen uptake (VO2). BACKGROUND: The cardiac fixation of
      MIBG reflects presynaptic uptake and is reduced in heart failure. Whether it is
      related to exercise capacity and has better prognostic value than peak VO2 is
      unknown. METHODS: Ninety-three patients with heart failure (ejection fraction
      <45%) were studied with planar MIBG imaging, cardiopulmonary exercise tests and
      hemodynamics (n = 44). Early (20 min) and late (4 h) MIBG acquisition, as well as
      their ratio (washout, WO) were determined. Prognostic value was assessed by
      survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses.
      RESULTS: Late cardiac MIBG uptake was reduced (131+/-20%, normal values 192+/
      42%) and correlated with ejection fraction (r = 0.49), cardiac index (r = 0.40)
      and pulmonary wedge pressure (r = -0.35). There was a significant correlation
      between peak VO2 and MIBG uptake (r = 0.41, p < 0.0001). With a mean follow-up of
      10+/-8 months, both late MIBG uptake (p = 0.04) and peak VO2 (p < 0.0001) were
      predictive of death or heart transplantation, but only peak VO2 emerged by
      multivariate analysis. Neither early MIBG uptake nor WO yielded significant
      insights beyond those provided by late MIBG uptake. CONCLUSIONS:
      Metaiodobenzylguanidine uptake has prognostic value in patients with wide ranges
      of heart failure, but peak VO2 remains the most powerful prognostic index.

PMID- 10080479
TI  - Catheter-induced mechanical trauma to accessory pathways during radiofrequency
      ablation: incidence, predictors and clinical implications.
AB  - OBJECTIVES: To evaluate the incidence, predictors and clinical implications of
      nonintentionally catheter-induced mechanical trauma to accessory pathways during
      radiofrequency ablation procedures. BACKGROUND: Data on the incidence and
      significance of catheter-induced trauma to accessory pathways are scarce.
      METHODS: Consecutive patients (n = 381) undergoing radiofrequency ablation of
      accessory pathways at two different institutions were closely monitored for
      appearance of mechanical block of accessory pathways during catheter
      manipulation. RESULTS: Mechanical trauma to accessory pathways was observed in 37
      (9.7%) patients. According to a multivariate analysis, the only independent
      variable associated with this phenomenon was the anatomical pathway location (p =
      0.0001). The incidence of trauma of either right anteroseptal (38.5%) or right
      atriofascicular pathways (33.3%) was significantly greater than that of pathways
      (< or =10%) at all remaining locations (p < 0.0001). The duration of conduction
      block observed ranged from < or =1 min to >30 min in 19% and 35% of patients,
      respectively. "Immediate" application of radiofrequency pulses at sites of
      mechanical block (<1 min after occurrence) was associated with a 78% long-term
      success rate at follow-up. This contrasted with a 25% long-term success rate in
      patients in whom pulses were delivered 30 min after occurrence of block ("delayed
      pulses"). Finally, in 24% of patients persistent trauma-induced conduction block
      led to discontinuation of the ablation procedure. CONCLUSIONS: Trauma to
      accessory pathways is more common than previously recognized and frequently
      results in prolongation or discontinuation of the ablation procedure and in lower
      success rates. The only independent predictor of catheter-trauma to accessory
      pathways is the pathway location.

PMID- 10080480
TI  - A technique for the rapid diagnosis of atrial tachycardia in the
      electrophysiology laboratory.
AB  - OBJECTIVE: The purpose of this study was to determine if the atrial response upon
      cessation of ventricular pacing associated with 1:1 ventriculoatrial conduction
      during paroxysmal supraventricular tachycardia is a useful diagnostic maneuver in
      the electrophysiology laboratory. BACKGROUND: Despite various maneuvers, it can
      be difficult to differentiate atrial tachycardia from other forms of paroxysmal
      supraventricular tachycardia. METHODS: The response upon cessation of ventricular
      pacing associated with 1:1 ventriculoatrial conduction was studied during four
      types of tachycardia: 1) atrioventricular nodal reentry (n = 102), 2) orthodromic
      reciprocating tachycardia (n = 43), 3) atrial tachycardia (n = 19) and 4) atrial
      tachycardia simulated by demand atrial pacing in patients with inducible
      atrioventricular nodal reentry or orthodromic reciprocating tachycardia (n = 32).
      The electrogram sequence upon cessation of ventricular pacing was, categorized as
      "atrial-ventricular" (A-V) or "atrial-atrial-ventricular" (A-A-V). RESULTS: The A
      V response was observed in all cases of atrioventricular nodal reentrant and
      orthodromic reciprocating tachycardia. In contrast, the A-A-V response was
      observed in all cases of atrial tachycardia and simulated atrial tachycardia,
      even in the presence of dual atrioventricular nodal pathways or a concealed
      accessory atrioventricular pathway. CONCLUSIONS: In conclusion, an A-A-V response
      upon cessation of ventricular pacing associated with 1:1 ventriculoatrial
      conduction is highly sensitive and specific for the identification of atrial
      tachycardia in the electrophysiology laboratory.

PMID- 10080481
TI  - Ventricular excitation maps using tissue Doppler acceleration imaging: potential
      clinical application.
AB  - OBJECTIVES: The purpose of this study is to validate the use of tissue Doppler
      acceleration imaging (TDAI) for evaluation of the onset of ventricular
      contraction in humans. BACKGROUND: Tissue Doppler acceleration imaging can
      display the distribution, direction and value of ventricular acceleration
      responses to myocardial contraction and electrical excitation. METHODS: Twenty
      normal volunteers underwent TDAI testing to determine the normal onset of
      ventricular acceleration. Two patients with paroxysmal supraventricular
      tachycardia and 30 patients with permanent pacemakers underwent introduction of
      esophageal and right ventricular pacing electrodes, respectively, and were
      studied to visualize the onset of pacer-induced ventricular acceleration. Eight
      patients with dual atrioventricular (AV) node and 20 patients with Wolff
      Parkinson-White (WPW) syndrome underwent TDAI testing to localize the abnormal
      onset of ventricular acceleration, and the results were compared with those of
      intracardiac electrophysiology (ICEP) tests. RESULTS: The normal onset and the
      onset of dual AV node were localized at the upper interventricular septum (IVS)
      under the right coronary cusp within 25 ms before the beginning of the R wave in
      the electrocardiogram (ECG). In all patients in the pacing group, the location
      and timing of the onset conformed to the positions and timing of electrodes
      (100%). In patients with WPW syndrome, abnormal onset was localized to portions
      of the ventricular wall other than the upper IVS at the delta wave or within 25
      ms after the delta wave in the ECG. The agreement was 90% (18 of 20) between the
      abnormal onset and the position of the accessory pathways determined by ICEP
      testing. CONCLUSIONS: These results suggest that TDAI is a useful noninvasive
      method that frequently is successful in visualizing the intramural site of origin
      of ventricular mechanical contraction.

PMID- 10080482
TI  - A critical appraisal of the quality of the management of infective endocarditis.
AB  - OBJECTIVES: The purpose of this study was to assess the quality of the management
      of infective endocarditis. BACKGROUND: Although many guidelines on the management
      of infective endocarditis exist, the quality of this management has not been
      evaluated. METHODS: We collected data on all patients (116) hospitalized with
      infective endocarditis over 1 year in all hospitals in the Rhone-Alpes region
      (France). RESULTS: Prophylactic antibiotics were not given before infective
      endocarditis to 8/11 cardiac patients at risk and who underwent an at risk
      procedure. Among the 55 cardiac patients at risk and with fever and who consulted
      a physician, blood cultures were not performed before antibiotic therapy was
      initiated for 32 patients. In-hospital antibiotic therapy was incorrect for 23
      patients. The portal of entry was not treated for 16/61 patients with an
      accessible portal of entry. Among the 19 patients who had severe heart failure or
      fever persisting more than 2 weeks in spite of antibiotic therapy and who could
      have undergone early surgery, surgery was delayed for five, and not performed for
      three. Overall, the average score was 15/20. CONCLUSIONS: More information on the
      management of infective endocarditis should be widely disseminated to the
      physicians' and the dentists' communities and to the patients at risk.

PMID- 10080483
TI  - Infective endocarditis: how well are we managing our patients?

PMID- 10080484
TI  - Abnormal flow-mediated epicardial vasomotion in human coronary arteries is
      improved by angiotensin-converting enzyme inhibition: a potential role of
      bradykinin.
AB  - OBJECTIVES: This study was performed to determine whether angiotensin converting
      enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation
      in patients with atherosclerosis or its risk factors and whether this is mediated
      by enhanced bradykinin activity. BACKGROUND: Abnormal coronary vasomotion due to
      endothelial dysfunction contributes to myocardial ischemia in patients with
      atherosclerosis, and its reversal may have an antiischemic action. Previous
      studies have shown that ACE inhibition improves coronary endothelial responses to
      acetylcholine, but whether this is accompanied by improved responses to shear
      stress remains unknown. METHODS: In 19 patients with mild atherosclerosis,
      metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated
      during separate intracoronary infusions of low-dose bradykinin (BK) and
      enalaprilat. Endothelium-dependent and -independent vasodilation was estimated
      with intracoronary BK and sodium nitroprusside respectively. RESULTS: Enalaprilat
      did not alter either resting coronary vascular tone or dilation with sodium
      nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that
      constricted abnormally with pacing (-5+/-1%) dilated (3+/-2%) with pacing in the
      presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5
      ng/min) that did not alter resting diameter in the constricting segments also
      improved the abnormal response to a 6+/-1% dilation (p < 0.001). Cardiac pacing
      induced reduction in coronary vascular resistance of 27+/-4% (p < 0.001) remained
      unchanged after enalaprilat. CONCLUSIONS: Thus ACE inhibition: A) selectively
      improved endothelium-dependent but not-independent dilation, and B) abolished
      abnormal flow-mediated epicardial vasomotion in patients with endothelial
      dysfunction, in part, by increasing endogenous BK activity.

PMID- 10080485
TI  - Endothelium-dependent relaxation by acetylcholine is impaired in
      hypertriglyceridemic humans with normal levels of plasma LDL cholesterol.
AB  - OBJECTIVES: Patients with high triglyceride (of which very low density
      lipoproteins [VLDL] are the main carriers), but with normal low density
      lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium
      function status. BACKGROUND: Very low density lipoproteins inhibit endothelium
      dependent, but not -independent, vasorelaxation in vitro. METHODS: Three groups
      were studied: 1) healthy volunteers (n = 10; triglyceride 1.24+/-0.14 mmol/liter,
      LDL cholesterol 2.99+/-0.24 mmol/liter); 2) hypertriglyceridemic (n = 11;
      triglyceride 6.97+/-1.19 mmol/liter, LDL cholesterol 2.17+/-0.2 mmol/liter, p <
      0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25+/-0.29 mmol/liter,
      LDL cholesterol 5.61+/-0.54 mmol/liter; p < 0.05) patients. Vasoactive responses
      to acetylcholine, sodium nitroprusside, noradrenaline, N(G)-monomethyl-L-arginine
      and postischemic hyperemia were determined using forearm venous occlusion
      plethysmography. RESULTS: Responses to acetylcholine (37 microg/min) were
      significantly dampened both in hypercholesterolemic (% increase in forearm blood
      flow: 268.2+/-62) and hypertriglyceridemic patients (232.6+/-45.2) when compared
      with controls (547.8+/-108.9; ANOVA p < 0.05). Responses to sodium nitroprusside
      (at 1.6 microg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic:
      168.7+/- 25.1 vs. 140.6+/-38.9 vs. 178.5+/-54.5% increase), noradrenaline, N(G)
      monomethyl-L-arginine and postischemic hyperemic responses were not different
      among the groups examined. CONCLUSIONS: Acetylcholine responses are impaired in
      patients with pathophysiologic levels of plasma triglycerides but normal plasma
      levels of LDL cholesterol. The impairment observed was comparable to that
      obtained in hypercholesterolemic patients. We conclude that impaired responses to
      acetylcholine normally associated with hypercholesterolemia also occur in
      hypertriglyceridemia. These findings identify a potential mechanism by which high
      plasma triglyceride levels may be atherogenic independent of LDL cholesterol
      levels.

PMID- 10080486
TI  - Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator
      testing.
AB  - OBJECTIVES: We compared the ability of inhaled nitric oxide (NO), oxygen (O2) and
      nitric oxide in oxygen (NO+O2) to identify reactive pulmonary vasculature in
      pulmonary hypertensive patients during acute vasodilator testing at cardiac
      catheterization. BACKGROUND: In patients with pulmonary hypertension, decisions
      regarding suitability for corrective surgery, transplantation and assessment of
      long-term prognosis are based on results obtained during acute pulmonary
      vasodilator testing. METHODS: In group 1, 46 patients had hemodynamic
      measurements in room air (RA), 100% O2, return to RA and NO (80 parts per million
      [ppm] in RA). In group 2, 25 additional patients were studied in RA, 100% O2 and
      80 ppm NO in oxygen (NO+O2). RESULTS: In group 1, O2 decreased pulmonary vascular
      resistance (PVR) (mean+/-SEM) from 17.2+/-2.1 U.m2 to 11.1+/-1.5 U.m2 (p < 0.05).
      Nitric oxide caused a comparable decrease from 17.8+/-2.2 U.m2 to 11.7+/-1.7 U.m2
      (p < 0.05). In group 2, PVR decreased from 20.1+/-2.6 U.m2 to 14.3+/-1.9 U.m2 in
      O2 (p < 0.05) and further to 10.5+/-1.7 U.m2 in NO+O2 (p < 0.05). A response of
      20% or more reduction in PVR was seen in 22/25 patients with NO+O2 compared with
      16/25 in O2 alone (p = 0.01). CONCLUSIONS: Inhaled NO and O2 produced a similar
      degree of selective pulmonary vasodilation. Our data suggest that combination
      testing with NO + O2 provides additional pulmonary vasodilation in patients with
      a reactive pulmonary vascular bed in a selective, safe and expeditious fashion
      during cardiac catheterization. The combination of NO+O2 identifies patients with
      significant pulmonary vasoreactivity who might not be recognized if O2 or NO were
      used separately.

PMID- 10080487
TI  - Follow-up results of transvenous occlusion of patent ductus arteriosus with the
      buttoned device.
AB  - OBJECTIVES: The purpose of this presentation is to document results of buttoned
      device (BD) occlusion of patent ductus arteriosus (PDA) in a large number of
      patients with particular emphasis on long-term follow-up in an attempt to provide
      evidence for feasibility, safety and effectiveness of this method of PDA closure.
      BACKGROUND: Immediate and short-term results of BD occlusion of PDA have been
      documented in a limited number of children. METHODS: During a six-year period
      ending August 1996, transcatheter BD closure of PDA was attempted in 284
      patients, ages 0.3 to 92 years (median 7) under a protocol approved by the local
      institutional review boards and FDA with an investigational device exemption in
      U.S. cases. RESULTS: The PDAs measured 1 to 15 mm (median 4) at the narrowest
      diameter; 20 were larger than 8 mm and 10 larger than 10 mm. They were occluded
      with devices measuring from 15 to 35 mm delivered via 7F (N = 140) or 8F (N =
      144) sheaths. Successful implantation of the device was accomplished in 278 (98%)
      of 284 patients. The Qp:Qs decreased from 1.8+/-0.6 (mean+/-SD) to 1.09+/-0.19 (p
      < 0.001). Effective occlusion defined as no (N = 167 [60%]) or trivial (N = 79
      [28%]) residual shunt was achieved in 246 (88%) patients. All types of PDAs,
      irrespective of the shape (conical, tubular or short), size (small or large) or
      length (short or long) of the PDA and previously implanted Rashkind devices,
      could be occluded. Follow-up data, 1 to 60 months (median 24) after device
      implantation, were available in 234 (84%) patients. Seven (3%) patients required
      reintervention to treat residual shunt with (N = 2) or without (N = 5) hemolysis.
      Actuarial reintervention-free rates were 95% at 1 and 5 years. There was gradual
      reduction of actuarial residual shunts and were 40%, 28%, 21%, 14%, 11%, 10%, 6%
      and 0% respectively at 1 day, 1, 6, 12, 24, 36, 48 and 60 months after device
      implantation. Incorporation of folding plug over the button loop in 10 additional
      patients produced immediate and complete occlusion of PDA. CONCLUSIONS: This
      large multiinstitutional experience confirms the feasibility, safety and
      effectiveness of buttoned device closure of PDAs. All types of PDAs irrespective
      of the shape, length and diameter can be effectively occluded. Incorporation of
      folding plug over the button loop produces complete PDA occlusion at the time of
      device implantation.

PMID- 10080488
TI  - Biventricular repair approach in ducto-dependent neonates with hypoplastic but
      morphologically normal left ventricle.
AB  - OBJECTIVES: Increased afterload and multilevel LV obstruction is constant. We
      assumed that restoration of normal loading conditions by relief of LV
      obstructions promotes its growth, provided that part of the cardiac output was
      preoperatively supported by the LV, whatever the echocardiographic indexes.
      BACKGROUND: Whether to perform uni- or biventricular repair in ducto dependent
      neonates with hypoplastic but morphologically normal LV (hypoplastic left heart
      syndrome classes II & III) remains unanswered. Echocardiographic criteria have
      been proposed for surgical decision. METHODS: Twenty ducto dependent neonates
      presented with this anomaly. All had aortic coarctation associated to multilevel
      LV obstruction. Preoperative echocardiographic assessment showed: mean EDLW of
      12.4 +/- 3.03 ml/m2 and mean Rhodes score of -1.73 +/-0.8. Surgery consisted in
      relief of LV outflow tract obstruction by coarctation repair in all associated to
      aortic commissurotomy in one and ASD closure in 2. RESULTS: There were 3 early
      and 2 late deaths. Failure of biventricular repair and LV growth was obvious in
      patients with severe anatomic mitral stenosis. The other demonstrated growth of
      the left heart. At hospital discharge the EDLVV was 19.4+/-3.12 ml/m2 (p =
      0.0001) and the Rhodes score was -0.38+/-1.01 (p = 0.0003). Actuarial survival
      and freedom from reoperation rates at 5 years were 72.5% and 46%, respectively.
      CONCLUSIONS: Biventricular repair can be proposed to ducto dependent neonates
      with hypoplastic but morphologically normal LV provided that all anatomical
      causes of LV obstruction can be relieved. Secondary growth of the left heart then
      occurs; however, the reoperation rate is high.

PMID- 10080489
TI  - Echocardiography-derived left ventricular end-systolic regional wall stress and
      matrix remodeling after experimental myocardial infarction.
AB  - OBJECTIVES: We tested the hypothesis that regional end-systolic left ventricular
      (ESLV) wall stress is associated with extracellular matrix remodeling activity
      after myocardial infarction (MI). BACKGROUND: Increased left ventricular (LV)
      wall stress is a stimulus for LV enlargement, and echocardiography can be used to
      estimate regional wall stress. A powerful validation of a noninvasive method of
      estimating wall stress would be predicting cellular responses after a MI.
      METHODS: Echocardiographic images were obtained in rats 1, 7, 14 or 21 days after
      coronary ligation (n = 11) or sham surgery (n = 5). End-systolic left ventricular
      wall stress was calculated by finite element analysis in three regions
      (infarcted, noninfarcted and border) from short-axis images. Matrix
      metalloproteinase-9 (MMP-9) and macrophage density were determined by
      immunohistochemistry, and positive cells were counted in high power fields (hpf).
      RESULTS: Average ESLV wall stress was higher in rats with MI when compared to
      shams irrespective of time point (p < 0.01), and ESLV wall stress in the
      infarcted regions increased with time (25.1 +/- 5.9 vs. 69.9 +/- 4.4 kdyn/cm2,
      day 1 vs. 21; p < 0.01). Matrix metalloproteinase-9 expression was higher in
      infarcted and border regions when compared to noninfarcted regions (22.1 vs. 25.7
      vs. 0.10 cells/hpf, respectively; p < 0.01). Over all regions, ESLV wall stress
      was associated with MMP-9 (r = 0.76; p < 0.001), macrophage density (r = 0.72; p
      < 0.001) and collagen content (r = 0.67; p < 0.001). End-systolic left
      ventricular wall stress was significantly higher when MMP-9 positive cell density
      was greater than 10 cells/hpf (45+/-20 vs. 14+/-10 kdyn/cm2; p < 0.001).
      CONCLUSIONS: Regional increases in ESLV wall stress determined by
      echocardiography-based structural analysis are associated with extracellular
      matrix degradation activity.

PMID- 10080490
TI  - Chordal force distribution determines systolic mitral leaflet configuration and
      severity of functional mitral regurgitation.
AB  - OBJECTIVES: The purpose of this study was to investigate the impact of the
      chordae tendineae force distribution on systolic mitral leaflet geometry and
      mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is
      caused by changes in several elements of the valve apparatus. Interaction among
      these have to comply with the chordal force distribution defined by the chordal
      coapting forces (F(c)) created by the transmitral pressure difference, which
      close the leaflets and the chordal tethering forces (FT) pulling the leaflets
      apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular
      model where leading edge chordal forces measured by dedicated miniature force
      transducers were controlled by changing left ventricular pressure and papillary
      muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to
      cover the leaflet orifice for a given leaflet configuration were determined by
      two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet
      area was used as expression for incomplete leaflet coaptation. Regurgitant
      fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed
      procedure statistics revealed a linear correlation between the sum of the chordal
      net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum -
      maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01
      [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted
      leaflet mobility, resulting in a tented leaflet configuration due to an apical
      and posterior shift of the coaptation line. Anterior leaflet coapting forces
      increased due to mitral leaflet remodeling, which generated a nonuniform
      regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused
      functional mitral regurgitation based on tented leaflet configuration as observed
      clinically.

PMID- 10080491
TI  - Changes in porcine transmitral flow velocity pattern and its diastolic
      determinants during partial coronary occlusion.
AB  - OBJECTIVES: To define the mechanical determinants of transmitral flow and the
      effect of heart rate during regional ischemia. BACKGROUND: Myocardial ischemia
      changes the transmitral flow velocity pattern due to disease-induced changes in
      the heart's diastolic properties. METHODS: Regional ischemia was produced in 12
      pigs by partially occluding the left anterior descending coronary artery until
      segment-length shortening in the ischemic region fell by 20%. Transmitral flow
      velocity patterns and their determinants were measured under two conditions,
      baseline and ischemia, at two heart rates, 70 and 90 beats/min. RESULTS: Regional
      ischemia had a significant effect on two determinants of filling: relaxation,
      which was slower, and chamber stiffness, which increased. These changes were
      associated with reduced contractility and increased myocardial stiffness,
      resulting in an early transmitral flow pattern that was flatter and narrower, but
      no change in the late flow pattern. Moderate increases in heart rate accelerated
      relaxation and decreased atrioventricular pressure gradient but had no effect on
      contractility or myocardial or chamber stiffness, resulting in an early
      transmitral flow pattern that was flatter and narrower and an increased late flow
      velocity. CONCLUSIONS: This model of regional ischemia leads to a flatter and
      narrower early transmitral flow velocity pattern and no change in late flow due
      to a combination of slowed left ventricular relaxation and increased chamber
      stiffness. Reflex increases in heart rate that accompany ischemia tend to mask
      this effect.

PMID- 10080492
TI  - In vivo targeting of acoustically reflective liposomes for intravascular and
      transvascular ultrasonic enhancement.
AB  - OBJECTIVES: The purpose of this study was to target acoustically reflective
      liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement.
      BACKGROUND: We have previously demonstrated the development of acoustically
      reflective liposomes that can be conjugated for site-specific acoustic
      enhancement. This study evaluates the ability of liposomes coupled to antibodies
      specific for different components of atherosclerotic plaques and thrombi to
      target and enhance ultrasonic images in vivo. METHODS: Liposomes were prepared
      with phospholipids and cholesterol using a dehydration/ rehydration method.
      Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2
      pyridyldithio) propionate resulting in a thioether linkage between the protein
      and the phospholipid. Liposomes were conjugated to antifibrinogen or anti
      intercellular adhesion molecule-1 (anti-ICAM-1). In a Yucatan miniswine model,
      atherosclerosis was developed by crush injury of one carotid and one femoral
      artery and ingestion of a hypercholesterolemic diet. After full plaque
      development the arteries were imaged (20-MHz intravascular ultrasound catheter
      and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated
      liposomes and antibody conjugated liposomes. RESULTS: Conjugated liposomes
      retained their acoustically reflective properties and provided ultrasonic image
      enhancement of their targeted structures. Liposomes conjugated to antifibrinogen
      attached to thrombi and fibrous portions of the atheroma, whereas liposomes
      conjugated to anti-ICAM-1 attached to early atheroma. CONCLUSIONS: Our data
      demonstrate that this novel acoustic agent can provide varying targeting with
      different antibodies with retention of intravascular and transvascular acoustic
      properties.

PMID- 10080493
TI  - Role of nitric oxide in restenosis after experimental balloon angioplasty in the
      hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular
      remodeling.
AB  - OBJECTIVES: The purpose of this study was to assess the effects of L-arginine and
      N(G)-nitro-L-arginine methyl ester (L-NAME) on neointimal hyperplasia and
      vascular remodeling after balloon angioplasty in the hypercholesterolemic rabbit.
      BACKGROUND: Restenosis after balloon angioplasty is a consequence of both
      neointimal hyperplasia and vessel remodeling. Nitric oxide inhibits neointimal
      hyperplasia, but its effect on vessel remodeling is unknown. METHODS: Six weeks
      after induction of bilateral iliac atherosclerosis, 48 rabbits underwent
      successful angioplasty in 75 vessels. Eight rabbits (acute group) were sacrificed
      immediately after angioplasty. The remaining animals received either placebo
      (chronic control group), or a diet supplemented with either L-arginine (1.5
      g/kg/day), or L-NAME (15 mg/kg/day) for 4 weeks after angioplasty. RESULTS: The
      intimal area was significantly greater in the chronic control group compared to
      the acute group (2.60+/-1.03 mm2 vs. 1.35+/-0.62 mm2). This increase in intimal
      area was lower in the L-arginine group (1.79+/-0.61 mm2), and greater in the L
      NAME group (3.23+/-0.92 mm2). The area circumscribed by the internal elastic
      lamina (IEL) increased significantly in the control group compared to the acute
      group (from 2.52+/-0.66 to 3.33+/-0.85 mm2); a more marked increase occurred in
      the L-NAME group (3.90+/-0.85 mm2). By contrast, IEL area was unchanged in the L
      arginine group (2.41+/-0.62 mm2). As a result, there was no significant
      difference in lumen area after 4 weeks in the chronic groups (control: 0.74+/
      0.38 mm2; L-arginine: 0.50+/-0.43 mm2; L-NAME: 0.48+/-0.42 mm2). CONCLUSIONS: Our
      results demonstrate that L-arginine inhibits whereas L-NAME stimulates neointimal
      hyperplasia after experimental balloon angioplasty in the hypercholesterolemic
      rabbit. However, the lack of vessel enlargement in the L-arginine group resulted
      in a similar final lumen size in the L-NAME and L-arginine groups.

PMID- 10080494
TI  - Improved accuracy and precision of thermodilution cardiac output measurement
      using a dual thermistor catheter system.
AB  - OBJECTIVES: To assess whether thermodilution cardiac output determination based
      on measurement of injectate temperature in vivo leads to more accurate and
      precise estimates and to study the influence of chilled injectate on test
      performance. BACKGROUND: Cardiac output measurement via right heart
      catheterization is used extensively for hemodynamic evaluation in a variety of
      diagnostic, perioperative and critical care settings. Maximizing accuracy is
      essential for optimal patient care. METHODS: This prospective study of 960
      thermodilution cardiac output measurements was conducted using conventional and
      dual thermistor techniques. Specialized dual thermistor right heart catheters
      were constructed using a second thermistor positioned to measure injectate
      temperature in vivo just prior to entry into the right atrium. To eliminate
      interinjection variability, a custom set-up was developed that permitted output
      measurement using both techniques simultaneously. Both ambient temperature
      injections and cooled injections were investigated. RESULTS: The dual thermistor
      technique demonstrated significantly less measurement variability than the
      conventional technique for both ambient temperature (precision = 0.41 vs. 0.55
      L/min, p < 0.001) and cooled (precision = 0.35 vs. 0.43 L/min, p = 0.01)
      injections. Similarly, the average range of cardiac output values obtained during
      five sequential injections in each patient was less using the dual thermistor
      approach (1.05 vs. 1.55 L/min, p < 0.001). The use of cooled injectate reduced
      the mean error of the dual thermistor technique but actually increased the mean
      error of the conventional technique. Even with ambient temperature injections,
      injectate warming during catheter transit varied considerably and unpredictably
      from injection to injection (2 SD range = -0.22 to 5.74 degrees C). Conventional
      ambient temperature and cooled measurements significantly overestimated Fick
      cardiac output measurements by 0.32 and 0.50 L/min, respectively (p < 0.001). In
      contrast, dual thermistor measurements were statistically similar (-0.08 and 
      0.08 L/min, p = 0.34) to Fick measurements. CONCLUSIONS: This new dual thermistor
      approach results in a significant improvement in both precision and accuracy of
      thermodilution cardiac output measurement.

PMID- 10080495
TI  - Salvaging the history, physical examination and doctor-patient relationship in a
      technological cardiology environment.

PMID- 10080496
TI  - "We have the best doctors and the most advanced technology"--advertising in
      medicine.

PMID- 10080497
TI  - President's page: Evaluation and management documentation guidelines: proving
      accountability or just increasing hassle?

PMID- 10080498
TI  - "Care," cancer and coenzyme Q10.

PMID- 10080499
TI  - Aortic atheromas and historical justice.

PMID- 10080500
TI  - The malpractice crisis and the "expert" witness: the problem and a proposed
      solution.

PMID- 10080501
TI  - The influence of age and gender on heart rate variability (HRV)

PMID- 10080502
TI  - Cost-effectiveness of an ineffective therapy(?)

PMID- 10080503
TI  - Ictal patterns of neocortical seizures monitored with intracranial electrodes:
      correlation with surgical outcome.
AB  - PURPOSE: Numerous factors have been analyzed in attempts to predict the outcome
      of surgical resections in patients with neocortical epilepsy. We examined the
      correlation between surgical outcome and electrocorticographic features of
      neocortical ictal patterns. METHODS: Twenty six patients with neocortical
      epilepsy underwent monitoring with subdural grid electrodes before surgery. Ictal
      patterns were analyzed retrospectively and correlated with three types of
      outcome: seizure free, worthwhile improvement (>75% reduction of seizure
      frequency), and no worthwhile improvement. The duration of follow-up was 2-5
      years. RESULTS: Ictal patterns were divided according to the size of
      epileptogenic zone (focal, regional, multifocal); velocity and type of seizure
      propagation (fast contiguous, slow contiguous, noncontiguous); pattern of the
      onset of ictal activity; part of the cortex involved in the origin of the seizure
      (frontal, frontocentroparietal, etc.). Spread to medial temporal structures (as
      assessed by subtemporal strips) also was evaluated in selected cases.
      Statistically significant correlation with surgical outcome (p = 0.026) was shown
      for only one variable: type of spread. Patients with slow spread (n = 8)
      demonstrated the best outcomes (five are seizure free), whereas patients with
      noncontiguous spread (n = 5) demonstrated the worst outcomes (four did not
      improve significantly). Patients with fast contiguous spread (n = 13) showed
      intermediate outcomes. CONCLUSIONS: Types of propagation of ictal neocortical
      activity correlate with surgical outcome. Analysis of ictal pattern during
      intracranial recordings may help to predict surgical outcome for neocortical
      epilepsy.

PMID- 10080504
TI  - Periictal SPECT localization verified by simultaneous intracranial EEG.
AB  - PURPOSE: We investigated whether blood-flow changes measured by ictal or
      immediate postictal single photon emission computed tomography (SPECT) reflect
      with accuracy the actual location of ictal discharge as measured by simultaneous
      intracranial EEG. In addition, we evaluated the reliability of ictal SPECT
      obtained with implanted electrodes by comparing results with those of ictal SPECT
      performed during scalp EEG monitoring in selected patients. METHODS: Eleven
      patients with intractable partial epilepsy who had both ictal and interictal
      SPECT scans during invasive EEG monitoring were studied. We analyzed perfusion
      differences based on registration, normalization, and subtraction of periictal
      and interictal SPECT images. SPECT results were interpreted in relation to
      location and evolution of ictal EEG change, as reflected by simultaneous
      intracranial EEG. In five patients, we also compared ictal SPECT results that
      were obtained during both scalp and intracranial EEG monitoring. RESULTS: In 10
      of 11 patients, localized increases or decreases in blood flow or both were
      identified in regions of ongoing or prior seizure discharge, respectively, at the
      time of SPECT brain perfusion. In one patient, SPECT localization could not be
      verified by the available electrode array. CONCLUSIONS: Localization of ictal
      discharge during or before SPECT injection accurately determines increase or
      decrease in perfusion, respectively, and both are of equal validity in reflecting
      the region of epileptic discharge. SPECT perfusion changes can be reliably
      obtained during intracranial monitoring.

PMID- 10080505
TI  - Visual and automatic investigation of epileptiform spikes in intracranial EEG
      recordings.
AB  - PURPOSE: Performance of automatic spike-detection algorithms and interrater
      reliability of human EEG reviewers were investigated previously by using scalp
      EEG recordings. However, it is not known, whether the findings of these studies
      hold for intracranial recordings. To address this question, we analyzed spike
      detection in intracranial recordings by two human reviewers and three automatic
      systems covering major lines in the development of automatic spike-detection
      systems. METHODS: Intracranial recordings from subdural and intrahippocampal
      depth electrode contacts in seven patients were analyzed by two reviewers and
      three spike-detection systems: (a) The rule-based system by Gotman, (b) a two
      stage system consisting of a linear predictor and a second rule-based stage, and
      (c) a system using wavelet coefficients of the intracranial EEG data. RESULTS:
      Agreement between the two human reviewers with respect to spike identification
      was <50%. The automatic systems achieved agreements of 24% (Gotman), 26% (wavelet
      detector), and 32% (two-stage system) with the individual human reviewers. In
      spite of the small proportion of agreements, the same anatomic regions were
      identified by human and automatic EEG analysis as generators for the majority of
      spikes. CONCLUSIONS: The poor agreement between the human EEG reviewers suggests
      that the definition of spikes and spike-like episodes in intracranial electrodes
      is far from unequivocal. Nevertheless, localizing information is highly
      consistent by either visual or automatic spike detection, independent of the
      algorithm used for automatic spike detection.

PMID- 10080506
TI  - Occurrence, outcome, and prognostic factors of infantile spasms and Lennox
      Gastaut syndrome.
AB  - PURPOSE: To analyze the occurrence, outcome, and prognostic factors of infantile
      spasms (IS) and the Lennox-Gastaut syndrome (LGS) in a defined population.
      METHODS: All children treated because of IS and LGS in the Department of
      Pediatrics, University of Oulu, from January 1, 1976, until December 31, 1993,
      who came from the primary catchment area of the hospital were included. Detailed
      information concerning their individual pre-, peri-, and postnatal medical
      histories and medical and laboratory examinations were compiled. RESULTS: Thirty
      seven children (18 boys) had IS, and 25 (14 boys) had LGS. The occurrence of IS
      of 0.41/1,000 live births 195% confidence interval (CI), 0.29-0.57/1,000] did not
      differ significantly from that of LGS, which was 0.28/1,000 live births (95% CI,
      0.18-0.41/1,000). Ten (27%) of the 37 patients with IS evolved to LGS, which was
      40% of the LGS cases. All the 10 children with both IS and LGS had symptomatic
      epilepsy, were mentally retarded, and had active epilepsy at the end of
      approximately 10 years' follow-up. Twenty-six (87%) of the 30 symptomatic IS
      cases and all the 17 symptomatic LGS cases were due to either congenital or
      genetic etiologies. The outcome in cryptogenic IS cases was favorable; the risk
      for a poor neurologic and mental outcome was extremely low; odds ratio, 0.015
      (95% Cl, 0.001-0.196), as it was for therapy-resistant epilepsy; odds ratio,
      0.013 (95% CI, 0.001-0.166). In LGS patients, cryptogenic etiology did not
      decrease the risk for a poor outcome. CONCLUSIONS: Cryptogenic etiology is
      associated with a very low risk for a poor outcome in IS patients, but not in LGS
      patients. The outcome of IS children and the relation of IS to LGS are determined
      by the underlying brain disease, not by the epilepsy itself.

PMID- 10080507
TI  - The prognosis for control of seizures with medications in patients with MRI
      evidence for mesial temporal sclerosis.
AB  - PURPOSE: Mesial temporal sclerosis (MTS) is the most common and important
      pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance
      imaging (MRI) scans is strongly correlated with a successful surgical outcome.
      Despite the general assumption that patients with MTS respond poorly to
      medication, the long-term prognosis for such patients has not yet been
      investigated. We studied the overall clinical prognosis of patients with MTS and
      analyzed the factors related to the degree of medical responsiveness. METHODS:
      Case patients were actively followed up at the Yonsei Epilepsy Clinic in Seoul,
      Korea, for >2 years. A structured interview and a thorough clinical evaluation
      were conducted. MRI scans, at the field strength of 1.0 or 1.5 Tesla, were
      performed with T1- and T2-weighted coronal and axial spin-echo images. All
      coronal slices were < or = 5-mm thick with no gap. Two neurologists and one
      radiologist determined the presence of MTS in MRIs by visual analysis. RESULTS:
      The MTS group consisted of 104 patients. Of these, 26 (25%) were completely
      controlled with adequate therapy, and 40 (38%) were intractable, despite
      aggressive anticonvulsant polytherapy. The remaining 37% had their seizure
      frequencies reduced by > or = 50%, but were not seizure free. The age of seizure
      onset was significantly younger in the intractable group than in the well
      controlled group. Patients with a history of febrile convulsions or with
      epileptiform discharges in their electroencephalogram (EEG) had poorer seizure
      control (p < 0.05) than those who did not. Among the 16 patients who had no
      previous treatment, five (31%) became seizure free, and two were intractable.
      CONCLUSIONS: Not all patients with MTS are medically intractable; 25% of the
      patients in our study achieved complete control while receiving medication. Poor
      seizure control was related to an early age of seizure onset, a history of
      febrile convulsions, and epileptiform discharges on the EEG.

PMID- 10080508
TI  - Gelastic epilepsy: symptomatic and cryptogenic cases.
AB  - PURPOSE: To describe the etiology, characteristics, and clinical evolution of
      epilepsy in patients with gelastic seizures (GSs). METHODS: Nine patients whose
      seizures were characterized by typical laughing attacks were observed between
      1986 and 1997. Patients were selected based on electroencephalogram (EEG) or
      video-EEG recordings of at least one GS and on magnetic resonance imaging (MRI)
      study. RESULTS: Five patients were affected by symptomatic localization-related
      epilepsy (LRE), with four of the patients' disorders related to a hypothalamic
      hamartoma (HH) and one to tuberous sclerosis (TS) without evident hypothalamic
      lesions. In four patients (the cryptogenic cases) MRI was negative also in these
      cases, clinical and EEG data suggested a focal origin of the seizures. The
      epileptic syndrome in the HH cases was usually drug-resistant, and was surgically
      treated in two of the patients. The patient with TS became seizure free with
      vigabatrin. In the cryptogenic cases, the ictal, clinical, and EEG semiology were
      similar to the symptomatic cases: the clinical evolution was variable, with
      patients having transient drug resistance or partial response to treatment. No
      cognitive defects were observed in the cryptogenic patients. None of the nine
      patients had precocious puberty. CONCLUSIONS: We confirm the frequent finding of
      HHs in GSs and further underline how GSs may also be observed in patients without
      MRI lesions and with normal neurologic status. In these patients, clinical and
      EEG seizure semiology is similar to symptomatic cases, but the clinical evolution
      is usually more benign.

PMID- 10080509
TI  - Prediction of postoperative seizure control by hippocampal event-related
      potentials.
AB  - PURPOSE: In spite of unequivocal results of the presurgical evaluation, between
      10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become
      seizure free by temporal lobe surgery. Because event-related potentials (ERPs)
      recorded within the hippocampal formation have been shown to be sensitive to the
      epileptogenic process, we examined whether ERPs can help to improve the
      prediction of postoperative seizure control. METHODS: We recorded ERPs to words
      from bilateral intrahippocaampal electrodes by using a visual word-recognition
      paradigm in 70 patients with unilateral hippocampal pathology and related these
      measurements to seizure outcome after temporal lobe surgery. RESULTS: Words
      elicited N400 potentials, which were reduced in amplitude on repetition on the
      side contralateral to hippocampal sclerosis. This contralateral repetition
      effect, however, was significantly diminished in the group of patients who
      experienced seizure recurrence after the operation. Contralateral repetition
      effects thus permitted correct prediction of postoperative seizure control in 94%
      of all patients. CONCLUSIONS: Recording ERPs to words within the medial temporal
      lobes can improve the prediction of postoperative seizure control. Reduced
      repetition effects contralateral to the side of hippocampal sclerosis may
      indicate bilateral epileptogenicity.

PMID- 10080510
TI  - Valproate treatment and platelet function: the role of arachidonate metabolites.
AB  - PURPOSE: Valproate (VPA) is an extensively used drug in the therapy of
      epilepsies. One of the most frequently reported side effects of VPA is
      hemorrhagic diathesis. Some authors emphasized the decreased platelet count as
      the basis of VPA-induced hemorrhagic diathesis, but some reports suggested that a
      significant proportion of patients with normal platelet count may still have an
      altered platelet function. The mechanism of the VPA-induced platelet dysfunction
      has not yet been elucidated. A determining element of platelet functions is the
      arachidonate cascade. Present ex vivo experiments were designed to determine
      whether a relation exists between the incidence of hemostasis caused by VPA and
      the effect of this drug on the arachidonate cascade of platelets. METHODS:
      Platelets were isolated from patients receiving long-term VPA treatment (serum
      level, 36.04+/-16.12 microg/ml; n = 10) or carbamazepine (CBZ) treatment (serum
      level, 5.24+/-2.67 microg/ml; n = 10) and were labeled with [14C]arachidonic
      acid. (CBZ-treated patients were chosen as a control group, because CBZ causes
      blood dyscrasias similar to those elicited by VPA, but there has been no report
      that CBZ induces a platelet dysfunction.) The 14C-eicosanoids were separated by
      means of overpressure thin-layer chromatography and determined quantitatively by
      liquid scintillation. RESULTS: Even when the mean plasma concentration of the
      drug was low, VPA treatment reduced the activity of the arachidonate cascade in
      platelets. VPA effectively inhibited the cyclooxygenase pathway and the synthesis
      of the strong platelet aggregator thromboxane A2. CONCLUSIONS: Inhibition of the
      platelet arachidonate cascade may contribute to the platelet-function alterations
      caused by VPA.

PMID- 10080511
TI  - Once-daily versus twice-daily vigabatrin: is there a difference? The results of a
      double-blind pilot study.
AB  - PURPOSE: Vigabatrin (VGB) has been approved in Europe and is prescribed for
      either once or twice-daily administration. This choice has been based on the
      pharmacodynamic activity of VGB. The purpose of this study was to compare the
      efficacy and tolerability of these two different medication regimens. METHODS:
      The study design was a double-blind randomized two-period cross-over study in
      adults who had responded to add-on VGB for previously uncontrolled seizures. Each
      study period consisted of three months. Patients were maintained on the same
      daily dose of VGB to which they had demonstrated a clinical response. In addition
      to the primary efficacy criteria of seizure frequency on the two treatment
      regimens, this study included blinded ratings of overall efficacy and "well
      being" by both physician and patient. The primary tolerability criterion was the
      reported incidence of adverse events by phase. RESULTS: Fifty patients were
      initially entered into the study, and 13 patients withdrew before completion,
      only one reported as due to an adverse event. There was no statistical difference
      in seizure frequency or the tolerability of the medication. Blinded physician and
      patient rating scales for seizure control, and patient well being showed a
      nonstatistical trend toward once-daily administration as compared with twice
      daily administration. CONCLUSIONS: This clinical study provides support for the
      pharmacological evidence that this preparation may be administered on a once or
      twice daily basis, depending on the individual patient's preference, total dosage
      and co-medication.

PMID- 10080512
TI  - Cortical excitability in patients after loading doses of lamotrigine: a study
      with magnetic brain stimulation.
AB  - PURPOSE: Transcranial magnetic stimulation (TMS) of the brain allows the
      pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of
      motor corticospinal pathways to be evaluated in patients with epilepsy and normal
      subjects. However, no study has yet documented the changes in motor excitability
      in patients treated with lamotrigine (LTG). We aimed to study the effects of
      loading doses of LTG on TMS recordings in patients with epilepsy at the beginning
      of their treatment. METHODS: We investigated single-pulse TMS in six patients
      with complex partial seizures. The TMS recordings were performed in five sessions
      before and during 5 weeks of treatment. Motor threshold, motor-evoked potential
      (MEP) amplitude, cortical silent period, and peripheral conduction velocity were
      used as parameters of evaluation. LTG was started with a dosage of 25 mg/day
      until a daily maintenance dosage of 200 mg/day was reached. RESULTS: The motor
      threshold activation of thenar muscles was significantly increased by LTG after 2
      weeks of treatment and was increased in a parallel way to the loading dose of the
      drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles
      did not show significant changes at high- or low-intensity stimulation. The
      cortical silent period remained unchanged at low- and high-intensity stimulation.
      The absolute latency of MEPs after cortical and cervical stimulation was
      unchanged, as was the central motor conduction time. CONCLUSIONS: Our study
      documents that loading doses of LTG, administered as monotherapy, progressively
      increases patients' motor thresholds over short periods.

PMID- 10080513
TI  - Lamotrigine associated with insomnia.
AB  - PURPOSE: To review the incidence of lamotrigine (LTG)-associated insomnia in an
      adult tertiary care epilepsy outpatient clinic. METHODS: The records of all
      patients who had received LTG were reviewed to identify patients who had
      experienced insomnia after introduction of this drug. Patients were included if
      they had experienced a sleep disturbance of sufficient severity to require a
      discontinuation of LTG or a dose reduction. RESULTS: Among 109 patients exposed
      to LTG, seven (6.4%) had a sleep disturbance of a severity to required a change
      in therapy. The descriptions of the sleep disturbance were similar among the
      patients, and the LTG-induced insomnia appeared to be dose dependent. Unlike the
      few previous descriptions of LTG-induced insomnia in the literature, no factors
      predisposing to this adverse effect were identified. CONCLUSIONS: The results of
      this retrospective review suggest an association between LTG and intolerable
      insomnia in a small proportion of patients. Physicians should inquire about sleep
      disturbances in patients treated with LTG.

PMID- 10080514
TI  - Magnetoencephalography in presurgical evaluation of children with the Landau
      Kleffner syndrome.
AB  - PURPOSE: Our aim was (a) to localize the primary epileptogenic cortex for
      possible multiple subpial transsection in four children with the Landau-Kleffner
      syndrome (LKS), and (b) to evaluate the impact of magnetoencephalography (MEG) in
      the localizing process. METHODS: We used EEG to detect the overall epileptiform
      activity and MEG for selective recording of fissural spikes. The cortical
      generators of MEG spikes were modeled with dipoles, and their activation order
      was determined. The voltage distribution, consistent with the earliest MEG
      sources, was then identified during the course of the patient's EEG spikes to
      determine the relative timing between stereotypic EEG and MEG spikes and to
      distinguish the earliest (primary) source area among the secondary ones. RESULTS:
      In all patients, the earliest spike activity originated in the intrasylvian
      cortex, spreading in one subject to the contralateral sylvian cortex within 20
      ms. Secondary spikes occurred within 10-60 ms in ipsilateral perisylvian,
      temporooccipital, and parietooccipital areas. A single intrasylvian pacemaker
      initiated all epileptic activity in two patients, whereas the other two had
      independent left- and right-hemisphere circuits or focal spikes. MEG source
      dynamics predicted the results of the methohexital suppression test in two
      patients and was confirmed by surgery outcome in one patient, in whom all
      epileptic activity ceased after a small transsection of the sylvian pacemaker.
      CONCLUSIONS: (a) The intrasylvian cortex is a likely pacemaker of epileptic
      discharges in LKS, and (b) MEG provides useful presurgical information of the
      cortical spike dynamics in LKS patients.

PMID- 10080515
TI  - Depression in temporal lobe epilepsy before epilepsy surgery.
AB  - PURPOSE: This study examined the association of depression with laterality of
      epilepsy surgery in patients with temporal lobe epilepsy before standard
      lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for
      localization of epilepsy and eventual temporal lobectomy. Patients underwent
      routine neuropsychiatric evaluation blinded for epileptic focus, including
      ratings on depression. Patients were grouped according to right (n = 25, M = 10/F
      = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance
      included side of surgery as grouping variable and sex, general depressive,
      cognitive depressive, and vegetative depressive symptoms as dependent variables.
      Chi2 analyses included categoric variables of sex, handedness, education,
      neuropathologic findings, and current affective disorders. t Tests were performed
      on variables of age, epilepsy duration, and cognitive function. RESULTS: Right
      and left temporal epilepsy groups did not differ with regard to sex, handedness,
      age, duration of epilepsy, education, cognitive function, and neuropathology.
      Patients with right temporal epilepsy rated higher on general, cognitive. and
      vegetative depression scores. Women scored higher on general, cognitive, and
      vegetative depression scores. Current affective disorders were more common in the
      right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were
      more prominent in patients with right temporal lobe epilepsy and in women in
      particular. The strength of this laterality finding lies in the selection of
      patients, as all underwent epilepsy surgery. The finding on gender difference
      partly reflects the higher incidence of depression in women and needs further
      exploration. The laterality finding contrasts with recent findings in epilepsy,
      stroke, and trauma that associate depression with left hemispheric lesions.
      However, our results are consistent with findings in electrically hyperactive
      lesions such as gelastic and dacrystic epilepsy.

PMID- 10080516
TI  - Allergic skin reactions to anticonvulsant medications in patients receiving
      cranial radiation therapy.
AB  - PURPOSE: Erythema multiforme and Stevens-Johnson syndrome have been associated
      with anticonvulsant medications (AEDs) in patients with brain tumors receiving
      cranial irradiation. AEDs are also known to cause mild drug rashes. The incidence
      of these complications has not been well studied among patients with brain
      tumors. We reviewed the records of patients with brain tumors treated with
      cranial radiation and AEDs to assess the frequency of both severe and mild skin
      reactions. METHODS: Retrospective review of 289 radiotherapy records of
      consecutively treated patients from 1988 to 1993. RESULTS: Only one of 289
      patients developed erythema multiforme. Milder rashes, however, occurred in 18%
      of exposures to AEDs including 22% of exposures to phenytoin, compared with the
      expected rate of 5-10%. Most of the mild drug rashes occurred before the
      initiation of radiotherapy, suggesting that radiation was not the cause of these
      reactions. CONCLUSIONS: Severe skin rashes are rare among patients with brain
      tumors receiving radiation therapy and AEDs. There is, however, an increased
      frequency of mild drug rashes among patients with brain tumors that does not
      appear related to radiation.

PMID- 10080517
TI  - Elevated plasma concentrations of homocysteine in antiepileptic drug treatment.
AB  - PURPOSE: Homocysteine is an experimental convulsant and an established risk
      factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12,
      or folate leads to increased homocysteine plasma concentrations. During treatment
      with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these
      vitamins is common. The objective of the study was to test the hypothesis that
      antiepileptic drug (AED) treatment is associated with increased homocysteine
      plasma concentrations. METHODS: A total of 51 consecutive outpatients of our
      epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex-
      and age-matched controls were enrolled in the study. Concentrations of total
      homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were
      measured in the serum of fasted subjects. RESULTS: Patients and controls differed
      significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and
      vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of
      vitamin B12 were similar. The homocysteine plasma concentration was significantly
      increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5
      microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with
      concentrations of >15 microM was significantly higher in the patient group than
      among controls. The same result was obtained if only patients with CBZ
      monotherapy were included. Patients with increased homocysteine plasma
      concentrations had lower folate concentrations. CONCLUSIONS: These data support
      the hypothesis that prolonged AED treatment may increase plasma concentrations of
      homocysteine, although the alternative explanation that increased homocysteine
      plasma concentrations are associated with the disease and not the treatment
      cannot be completely excluded at the moment.

PMID- 10080518
TI  - Payer costs of patients diagnosed with epilepsy.
AB  - PURPOSE: To identify the annual cost to a third-party payer of inpatient and
      outpatient services and prescription drugs for patients diagnosed with epilepsy
      or convulsions. METHODS: Retrospective study using administrative and claims data
      from a private insurer in the Northeast United States with >1.8 million covered
      lives. Health plan members were included if they had a claim for epilepsy or
      convulsions and a claim for an antiepileptic drug (AED) between January 1992 and
      December 1996. Annual costs and frequencies of all medical services, and of
      services related to epilepsy, were compared among five groups of patients defined
      by the most intensive procedure they received: invasive therapeutic procedure
      (group 1); invasive diagnostic procedure without an invasive therapeutic
      procedure (group 2); noninvasive diagnostic procedure without an invasive
      procedure (group 3); neurologist or neurosurgeon visit without an invasive
      procedure or noninvasive diagnostic procedure (group 4); or none of the preceding
      services (group 5). RESULTS: In the cohort of 9,090 patients meeting the
      inclusion criteria, mean age was 38 years, 53% were female, 30% had malignant
      disease, and 25% had cardiac disease. The mean annual cost of all medical
      services was $9,617. Mean annual costs of all services were $43,333, $29,847,
      $11,300, $4,362, and $5,855, and annual costs of inpatient and outpatient
      encounters coded as epilepsy plus AEDs were $24,369, $10,330, $3,127, $1,079, and
      $1,086, in groups 1-5, respectively. Services used to stratify patients into the
      groups accounted for 37% of the total costs. CONCLUSIONS: The annual costs of
      medical services for patients with epilepsy are high and vary considerably
      because of treatment of epilepsy and management of comorbidities.

PMID- 10080519
TI  - Halothane as a neuroprotectant during constant stimulation of the perforant path.
AB  - PURPOSE: To determine the neuroprotective effects of halothane during constant
      stimulation of the perforant path. METHODS: Male Sprague-Dawley rats had
      electrodes implanted into the perforant path and dentate granule cell layer under
      halothane anaesthesia (1-2% in oxygen). They were then divided into four groups.
      In group 1 (n = 9), the perforant path was stimulated at 20 Hz for 2 h under
      halothane anaesthesia (1-2%). In group 2 (n = 3), the animals were unstimulated
      but maintained under halothane anaesthesia (1-2%) for 2 h with the electrodes in
      place. Both groups 1 and 2 had the electrodes removed and were then allowed to
      recover fully from the anaesthetic. In groups 3 and 4, the electrodes were held
      in place with dental acrylic. Both of these groups were allowed to recover fully
      from anaesthesia. In group 3 (n = 3), 24-48 h after recovery from anaesthesia,
      the perforant path was stimulated at 20 Hz for 2 h. Group 4 (n = 3) received no
      stimulation. After 14-17 days, the rats were killed, and morphometry and cell
      counts were performed on the hippocampi from rats in groups 1 and 2. RESULTS:
      Cell densities were not significantly different between control (group 2),
      unstimulated rats, and animals stimulated under halothane anaesthesia (group 1).
      Stimulation in the unanaesthetised rats resulted in severe neuronal loss in
      hilus, CA1, and CA3. CONCLUSIONS: Halothane protects hippocampal neurons against
      damage induced by constant stimulation of the perforant path.

PMID- 10080520
TI  - Surgical treatment of a case of early infantile epileptic encephalopathy with
      suppression-bursts associated with focal cortical dysplasia.
AB  - We report a surgically treated case of early infantile epileptic encephalopathy
      (EIEE) with suppression-bursts associated with focal cortical dysplasia. Tonic
      clonic seizures followed by a series of spasms occurred about a hundred times a
      day at a few days of age. Interictal electroencephalogram (EEG) revealed a
      suppression-burst pattern that was predominant in the left hemisphere. Magnetic
      resonance imaging (MRI) suggested focal cortical dysplasia in the left prefrontal
      area. Combination therapies with antiepileptic treatments showed only partial
      efficacy. The patient underwent lesionectomy at age 4 months, after which he
      gradually showed psychomotor development and a decrease of spasms to 0-2 series
      daily. In cases of EIEE with focal cortical dysplasia, surgical treatment may
      have beneficial effects on both psychomotor development and seizure control.

PMID- 10080521
TI  - Clinical significance of EEG abnormalities during photic stimulation in patients
      with photosensitive epilepsy.
AB  - PURPOSE: The continued presence of EEG abnormalities in patients with a history
      of photosensitive seizures is used to signify the persistence of photosensitive
      epilepsy. The extent to which this approach places patients at risk of seizures
      is unclear, however. We describe those EEG abnormalities that may be tolerated
      with low risk of further seizures, and those that are indicative of poor seizure
      control. METHODS: Fifty patients with EEG evidence of persistent photosensitive
      epilepsy underwent photosensitivity testing with diffuse and patterned light; 58%
      of patients continued to experience seizures, and 42% were seizure free. The
      incidence of EEG abnormalities to diffuse and patterned intermittent photic
      stimulation (IPS) was analysed as a function of recent seizures. RESULTS: All
      patients showed EEG abnormalities to patterned IPS; there was no significant
      association between patterned IPS and poor seizure control. EEG abnormalities to
      diffuse IPS occurred in 58% of patients, and 76% of these patients had
      experienced a seizure within the previous year. These patients were more than
      twice as likely to be poorly controlled than those who showed abnormalities only
      to patterned IPS. These results were consistent for both medicated and
      unmedicated patients. CONCLUSIONS: EEG abnormalities to patterned IPS can be used
      to signify the persistence of photosensitive epilepsy, but abnormalities to
      diffuse IPS are more likely to indicate the patient is poorly controlled and at
      risk of further seizures.

PMID- 10080522
TI  - Benign idiopathic partial epilepsy and brain lesion.
AB  - A 14-year-old girl had severe head trauma from a dog bite at the age of 9 days.
      This resulted in extensive brain damage, tetraplegia, mental retardation, and
      epilepsy. The seizures were of rolandic type, and the EEG showed multifocal sharp
      waves. The course was benign. The initial diagnosis of a pure symptomatic
      epilepsy was revised after demonstrating typical benign focal sharp waves in the
      EEG of the healthy sister. Thus a phenocopy of a benign partial epilepsy by the
      brain lesion could be excluded with sufficient certainty. This observation allows
      the conclusion that the genetic disposition underlying the sharp-wave trait
      characteristic of benign partial epilepsies can be involved also in the
      pathogenesis of seemingly pure symptomatic epilepsies. EEG studies on siblings of
      such patients are needed to exclude possible phenocopies.

PMID- 10080523
TI  - An angiographically occult arteriovenous malformation in the medial parietal lobe
      presenting as seizures of medial temporal lobe origin.
AB  - We present an unusual case of a patient who was diagnosed with temporal lobe
      epilepsy and whose seizures were reduced markedly after excision of an
      angiographically occult arteriovenous malformation (AVM) located in the left
      medial parietal lobe. A 38-year-old man had complex partial seizures
      characterized by motionless staring with oroalimentary and behavioral automatisms
      since the age of 15 years. Magnetic resonance imaging (MRI) demonstrated a small
      lesion extending from the left posterior cingulate gyrus to the precuneus. There
      was no MRI evidence of mesial temporal sclerosis. Intracranial EEG recordings
      showed ictal onset from the left medial parietal lobe propagating to the medial
      temporal lobes. Clinical signs appeared when these discharges reached the
      temporal lobes. After excision of the lesion (which was histologically confirmed
      as an AVM), together with the marginal cortex, seizures were reduced
      significantly. Careful diagnostic evaluation of lesions such as the this one may
      reveal an epileptogenic lesion (zone) far from the region where scalp ictal
      discharges seem to arise. In our case, we hypothesize that false localization was
      due to propagation of ictal discharges from the parietal focus through the limbic
      system.

PMID- 10080524
TI  - Morbus sacer in Africa: some religious aspects of epilepsy in traditional
      cultures.
AB  - Epilepsy when manifested as grand mal seizure provokes strong and ambivalent
      feelings in those witnessing it. Terms such as morbus sacer, denoting both a
      sacred and demoniac condition, or folk names indicating divine punishment, have
      expressed these feelings in European societies from antiquity to the Middle Ages
      and beyond. An atmosphere of fear, shame and mysticism surrounds epilepsy even in
      our days in many non-Western and also in Western cultures. In the course of work
      and studies in Tanzania, where I organized the Mahenge Clinic for Epilepsy in
      1960, and in other parts of Africa, I found that epilepsy is conceived of as an
      "African'' affliction, a manifestation of supernatural forces that makes it
      difficult to reach epilepsy sufferers with modern medical treatment. Epilepsy is
      traditionally looked on as caused by ancestral spirits or attributed to
      possession by evil spirits. It is also thought to be due to witchcraft, and
      "poisoning," and often taken to be contagious. Epilepsy may, under Christian
      missionary teaching, have come to be considered as due to demoniac possession or
      divine punishment for sins, in accordance with biblical examples. In many parts
      of Africa, syncretic amalgamation of indigenous traditions with Judeo-Christian
      doctrines influenced popular attitudes toward epilepsy. We demonstrated that
      persistent efforts at health education in the context of organized treatment of
      epilepsy can result in a change of popular notions about epilepsy and
      consequently lead to significant improvement in the quality of life of epilepsy
      sufferers.

PMID- 10080525
TI  - Nonepileptic seizures.

PMID- 10080526
TI  - Information value of scalp-recorded ictal EEG in unilateral mesiotemporal
      epilepsy.

PMID- 10080527
TI  - Pre-existing or epilepsy related problems have been attributed to AEDs.
      Antiepileptic drugs.

PMID- 10080528
TI  - Chemokine-induced phosphorylation of CC chemokine receptor 5 (CCR5).
AB  - The CC-chemokine receptor 5 (CCR5) mediates activation of T lymphocytes and
      macrophages by chemokines and is a major co-receptor for macrophage-tropic HIV-1
      strains. Recently, it was shown that the natural CCR5 ligands RANTES, macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and amino-terminal
      modifications of RANTES (Met-RANTES, AOP-RANTES) significantly differ in their
      abilities to induce sequestration of CCR5 from cellular surfaces. It was
      hypothesized that these findings may account for the observed differences between
      these molecules to inhibit HIV infectivity in vitro. Herein we review our work on
      early regulatory mechanisms that are initiated by ligand binding to CCR5 and
      that, conceptually, are involved in receptor endocytosis. A better understanding
      of these mechanisms may provide new therapeutic strategies to prevent HIV
      infection.

PMID- 10080529
TI  - Functions of Bruton's tyrosine kinase in mast and B cells.
AB  - Bruton's tyrosine kinase (Btk) plays crucial roles in B cell differentiation as
      well as mast cell activation through the high-affinity IgE receptor
      (FcepsilonRI). Defects in the btk gene lead to agammaglobulinemia (XLA) in humans
      and X-linked immunodeficiency (xid) in mice. Mast cells from xid and btk null
      mice exhibit mild defects in degranulation and severe impairments in the
      production of proinflammatory cytokines upon FcepsilonRI cross-linking. Recent
      studies demonstrated the role of Btk in a sustained increase in intracellular
      calcium concentrations in response to antigen receptor stimulation. Btk is also
      involved in the activation of stress-activated protein kinases, JNK/SAPK1/2, and
      thereby regulates c-Jun and other transcription factors that are important in
      cytokine gene activation. Regulation of the JNK/SAPK activation pathway by Btk
      may be related to the proapoptotic function of Btk in the programmed cell death
      in these hematopoietic cells.

PMID- 10080530
TI  - Stimulus-specific regulation of chemokine expression involves differential
      activation of the redox-responsive transcription factors AP-1 and NF-kappaB.
AB  - The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the
      redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown
      to be important for their expression. In this overview, we present evidence from
      our laboratories that the stimulus-specific regulation of these chemokines by the
      reactive oxidant H2O2, the proinflammatory cytokine TNF-alpha, and respiratory
      syncytial virus (RSV) is mediated in a cell type-specific manner involving
      different patterns of AP-1 and NF-kappaB binding activity. Our results
      demonstrate that H2O2 induction of IL-8 gene expression is linked with the
      selective binding of AP-1 to the IL-8 promoter, whereas TNF-alpha and RSV
      induction of IL-8 correlates with the activation of NF-kappaB binding. We propose
      that the differential activation and binding of inducible transcription factors
      to the promoter regions of chemokine genes provides a critical regulatory
      mechanism by which the CXC and CC chemokines can be selectively expressed in a
      cell type-specific and stimulus-specific manner. Such a regulatory mechanism of
      differential chemokine expression could critically influence the site-specific
      recruitment of distinct subsets of leukocytes to sites of inflammation and
      injury.

PMID- 10080531
TI  - P-selectin mediates neutrophil adhesion to endothelial cell borders.
AB  - During an acute inflammatory response, endothelial P-selectin (CD62P) can mediate
      the initial capture of neutrophils from the free flowing bloodstream. P-selectin
      is stored in secretory granules (Weibel-Palade bodies) and is rapidly expressed
      on the endothelial surface after stimulation with histamine or thrombin. Because
      neutrophil transmigration occurs preferentially at endothelial borders, we wished
      to determine whether P-selectin-dependent neutrophil capture (adhesion) occurs at
      endothelial cell borders. Under static or hydrodynamic flow (2 dyn/cm2)
      conditions, histamine (10(-4) M) or thrombin (0.2 U/mL) treatment induced
      preferential (> or = 75%) neutrophil adhesion to the cell borders of endothelial
      monolayers. Blocking antibody studies established that neutrophil adhesion was
      completely P-selectin dependent. P-selectin surface expression increased
      significantly after histamine treatment and P-selectin immunostaining was
      concentrated along endothelial borders. We conclude that preferential P-selectin
      expression along endothelial borders may be an important mechanism for targeting
      neutrophil migration at endothelial borders.

PMID- 10080532
TI  - Inhibition of IL-4-inducible gene expression in human monocytes by type I and
      type II interferons.
AB  - The Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce
      expression of a distinct subset of genes in human monocytes, including
      FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and
      type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN
      beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4
      and IL-13. However, the mechanism by which IFNs mediate this inhibition has not
      been defined. In this overview, we discuss the role of the transcription factor,
      STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and
      IL-13-induced gene expression in monocytes. We also discuss our recent findings
      that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by
      inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The
      ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity
      is dose- and time-dependent, and is not unique to monocytes because IFNs induce
      the same effects in fibroblasts. Inhibition of STAT6 activity is not evident
      unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation.
      Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement
      for de novo transcription. We propose a model in which stimulation of monocytes
      by IFN activates de novo synthesis of an inhibitory factor, possibly one or more
      members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of
      STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL
      4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit
      STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13
      inducible gene expression.

PMID- 10080533
TI  - Integrin signal transduction in myeloid leukocytes.
AB  - Integrin-mediated adhesion serves as a powerful costimulus for neutrophil
      activation. Clustering of integrins at the leukocyte membrane by interaction with
      surface-bound ligands (extracellular matrix proteins or endothelial cell counter
      receptors) leads to a number of signaling events that culminate in actin
      cytoskeletal rearrangement and neutrophil functional responses such as migration,
      degranulation, and respiratory burst. Although the signaling reactions elicited
      by integrin ligation are complex and the relative contribution of each pathway to
      neutrophil function is unclear, a large body of evidence suggests that activation
      of tyrosine kinases is a very proximal event in these signaling cascades. This
      review summarizes the role of adhesion in activating neutrophil functional
      properties and the contribution of leukocyte tyrosine kinases to regulation of
      integrin signaling in myeloid cells. Significant advances in our understanding of
      leukocyte integrin signaling have been afforded by studies using knockout mice
      lacking members of the Src-family of tyrosine kinases normally expressed in
      myeloid cells. These studies have demonstrated that these kinases (Hck, Fgr, and
      Lyn) are not required for myeloid cell development or for many of the functional
      properties of myeloid cells but are critical in controlling integrin-mediated
      signaling events. Absence of these kinases results in impaired adhesion-dependent
      neutrophil activation both in vivo and in vitro. These studies suggest that
      leukocyte-specific tyrosine kinases may be good therapeutic targets for
      controlling myeloid cell-dependent inflammatory disease.

PMID- 10080534
TI  - Multiple roles for PI 3-kinase in the regulation of PLCgamma activity and Ca2+
      mobilization in antigen-stimulated mast cells.
AB  - Cross-linking the IgE-bound FcepsilonRI with polyvalent antigen leads to Ca2+
      dependent degranulation from mast cells and basophils, initiating the allergic
      response. This overview addresses novel roles for PI 3-kinase in the regulation
      of signaling events that lie downstream of FcepsilonRI-mediated tyrosine kinase
      activation. The first novel role for PI 3-kinase is in the regulation of PLCgamma
      activity and is demonstrated by a dramatic inhibition of FcepsilonRI-induced
      Ins(1,4,5)P3 production after treatment of RBL-2H3 cells with wortmannin, a PI 3
      kinase inhibitor. We show that PI 3-kinase lipid products support Ins(1,4,5)P3
      production in at least two ways: by promoting translocation and phosphorylation
      of PLCgamma1 and by direct stimulation of both PLCgamma isoforms. In vitro
      stimulation of PLCgamma activity by PtdIns(3,4,5)P3 synergizes with activation by
      in vivo tyrosine phosphorylation for maximal enzymatic activity. A second novel
      role for PI 3-kinase is in the regulation of antigen-stimulated Ca2+ influx.
      Compared with control cells, Ca2+ responses are markedly diminished in antigen
      stimulated cells after wortmannin pretreatment. Differences include both a longer
      lag time to the initial elevation in Ca2+ after antigen and an inhibition of the
      sustained Ca2+ influx phase. However, thapsigargin challenge during the sustained
      phase demonstrates no difference in the state of the Ca2+ stores in antigen
      stimulated cells in the presence or absence of wortmannin. These data suggest
      that sufficient Ins(1,4,5)P3 is synthesized in wortmannin-treated cells to
      mobilize intracellular calcium stores and, furthermore, that the affected phase
      of Ca2+ influx is unlikely to be attributed to capacitative mechanisms. These
      data are consistent with a model where at least two pathways mediate Ca2+ influx
      in antigen-stimulated RBL-2H3 cells, one that is dependent on signals from empty
      stores (capacitative influx) and another that is downstream of PI 3-kinase.

PMID- 10080535
TI  - Regulation of arachidonic acid release and cytosolic phospholipase A2 activation.
AB  - The 85-kDa cytosolic PLA2 (cPLA2) mediates agonist-induced arachidonic acid
      release in many cell models, including mouse peritoneal macrophages. cPLA2 is
      regulated by an increase in intracellular calcium, which binds to an amino
      terminal C2 domain and induces its translocation to the nuclear envelope and
      endoplasmic reticulum. Phosphorylation of cPLA2 on S505 by mitogen-activated
      protein kinases (MAPK) also contributes to activation. In macrophages, zymosan
      induces a transient increase in intracellular calcium and activation of MAPK,
      which together fully activate cPLA2 and synergistically promote arachidonic acid
      release. There are alternative pathways for regulating cPLA2 in macrophages
      because PMA and okadaic acid induce arachidonic acid release without increasing
      calcium. The baculovirus expression system is a useful model to study cPLA2
      activation. Sf9 cells expressing cPLA2 release arachidonic acid to either A23187
      or okadaic acid. cPLA2 is phosphorylated on multiple sites in Sf9 cells, and
      phosphorylation of S727 is preferentially induced by okadaic acid. However, the
      phosphorylation sites are non-essential and only S505 phosphorylation partially
      contributes to cPLA2 activation in this model. Although okadaic acid does not
      increase intracellular calcium in Sf9 cells, calcium binding by the C2 domain is
      necessary for arachidonic acid release. A23187 and okadaic acid activate cPLA2 by
      different mechanisms, yet both induce translocation to the nuclear envelope in
      Sf9 cells. The results demonstrate that alternative regulatory pathways can lead
      to cPLA2 activation and arachidonic acid release.

PMID- 10080536
TI  - Signal transduction by reactive oxygen species in non-phagocytic cells.
AB  - A growing body of evidence suggests a potential role for oxygen-derived radicals
      such as superoxide anions and hydrogen peroxide as intracellular signaling
      molecules. Recently, progress has been made regarding the regulation of oxidant
      production in non-phagocytic cells. Significant gaps in understanding persist,
      however, especially in regard to the source(s) of oxidant production and the
      direct intracellular target(s) of oxygen radicals. Nonetheless, numerous recent
      studies have implicated a dynamic change in the intracellular redox state as an
      important determinant in a host of cellular decisions ranging from growth, to
      apoptosis, to cellular senescence.

PMID- 10080537
TI  - Sphingosine 1-phosphate: a prototype of a new class of second messengers.
AB  - Sphingosine 1-phosphate (SPP) is an important sphingolipid-derived second
      messenger in mammalian cells that acts to promote proliferation and to inhibit
      apoptosis. Various growth factors increase the intracellular concentration of SPP
      by activating sphingosine kinase, the molecular cloning of which has revealed
      that it defines a new type of lipid kinase. Cell fate is influenced by the
      balance between the intracellular concentration of SPP and that of ceramide, a
      pro-apoptotic sphingolipid metabolite. The observation that a similar "rheostat"
      is a determinant of cell survival in yeast cells exposed to heat shock indicates
      that it is an evolutionarily conserved mechanism of stress regulation. SPP also
      acts extracellularly to inhibit cell motility and to influence cell morphology,
      effects that appear to be mediated by the G protein-coupled receptor EDG1. These
      observations indicate that SPP is the prototype of a new class of lipid mediators
      that exert both intracellular and extracellular actions.

PMID- 10080538
TI  - Kinases involved in MSP/RON signaling.
AB  - Macrophage stimulating protein (MSP) belongs to the plasminogen-related kringle
      domain family. In addition to stimulation of macrophages, MSP acts on other cell
      types including epithelial and hematopoietic cells. The MSP receptor is a
      transmembrane tyrosine kinase called RON in humans and STK in mice. MSP/receptor
      interaction induces activation of signal transduction pathways that mediate MSP
      biological activities. Cytoplasmic kinases are intracellular messengers occupying
      an important role in signal transduction. We have identified kinases that
      participate in RON signaling. In addition to previously identified involvement of
      phosphatidylinositol 3-kinase (PI3-K), JNK, and MAPK, we found that FAK, c-Src,
      and AKT are rapidly and transiently activated by MSP. FAK, MAPK, and c-Src are
      involved in MSP-induced cell proliferation. MAPK and c-Src are components of one
      signal transduction cascade, and MAPK is downstream of c-Src. FAK also regulates
      MSP-induced cell growth, but via a path different from c-Src/MAPK. AKT kinase is
      a component of a separate branch of the RON/PI3-K pathway that mediates the MSP
      anti-apoptotic effect on epithelial cells. PI3-K regulates MSP-induced adhesion
      and motility but via downstream components different from AKT. Thus, occupancy of
      the RON receptor by MSP activates distinct signal transduction pathways that
      mediate several cellular responses.

PMID- 10080539
TI  - Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and
      chronic inflammation.
AB  - The objective of this study was to quantify, in vivo, constitutive and tumor
      necrosis factor alpha (TNF-alpha)-enhanced expression of mucosal addressin cell
      adhesion molecule-1 (MAdCAM-1) in different tissues from healthy wild-type mice
      (C57BL/6) as well as interleukin-10 (IL-10)-deficient mice with and without
      active colitis. Using the dual radiolabel monoclonal antibody technique, we found
      substantial constitutive expression of MAdCAM-1 in the intestine, colon, and
      mesenteric lymph nodes. MAdCAM-1 expression in these tissues was significantly
      enhanced, in a time-dependent manner, by systemic administration of TNF-alpha.
      Maximum surface expression was observed at 18 h after TNF-alpha administration
      and remained significantly elevated at 48 h post-TNF-alpha injection. No
      significant constitutive nor TNF-alpha-induced expression of MAdCAM-1 was
      detected in skeletal muscle, brain, or heart. In IL-10-deficient (IL-10 k/o) mice
      with no clinical or histological evidence of colitis, constitutive and TNF-alpha
      induced expression of MAdCAM-1 in the intestine, cecum, and colon was not
      different from those values obtained with healthy wild-type controls. IL-10
      deficient mice with active colitis exhibited a four- to fivefold greater
      expression of MAdCAM-1 in the cecum and colon compared with their healthy
      controls or to IL-10 k/o mice with no evidence of colitis. Taken together, these
      data demonstrate that TNF-alpha enhances surface expression of MAdCAM-1 in
      intestinal and colonic tissues to the same extent in both wild-type and IL-10 k/o
      mice with no colonic inflammation, whereas IL-10 k/o mice with active colitis
      exhibited a profound up-regulation of MAdCAM-1 in the colon.

PMID- 10080540
TI  - Antibodies to CD18 influence neutrophil migration through extracellular matrix.
AB  - Mac-1 (CD11b/CD18) is known to be involved in neutrophil (PMN) adhesion to
      endothelial cells and extracellular matrix. Although antibodies to CD 18 are
      being tested for therapy in humans, their role in PMN migration through the
      extracellular matrix is unknown. We used direct visualization to quantify PMN
      motility through reconstituted, three-dimensional gels of collagen type I. Gels
      were prepared with different concentrations of collagen (ranging from 0.1 to 1.0
      mg/mL) and PMN migration was examined in the presence and absence of antibodies
      to CD18 (anti-CD18), with and without stimulation by N-formyl peptides. In low
      concentration gels (<0.6 mg/mL), anti-CD18 had a significant influence on PMN
      migration, increasing motility in unstimulated PMN by 90% at 0.3 mg/mL collagen,
      and decreasing motility in N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      stimulated PMN by 70% at 0.4 mg/mL collagen. But antiCD18 had no effect on the
      rate of cell migration through high-concentration collagen gels (>0.6 mg/mL). PMN
      migration through collagen gels is CD18-dependent but only under conditions of
      high hydration, suggesting that CD18-mediated effects (e.g., adhesion to gel
      fibers) are only important when the fiber density is relatively low. Anti-CD18
      inhibited, but did not eliminate, the adhesion of fMLP-stimulated PMN to the
      surface of collagen gels, suggesting that cells use multiple mechanisms for
      gaining traction within the gel. Because of the multiple modes of interaction
      between motile cells and the deformable fiber matrix, blockade of one component,
      such as CD18, can enhance the rate of cell migration under one set of conditions,
      and inhibit under another.

PMID- 10080541
TI  - Neutrophils isolated from leprosy patients release TNF-alpha and exhibit
      accelerated apoptosis in vitro.
AB  - This study demonstrated that polymorphonuclear neutrophils (PMN) participate in
      the acute inflammatory response in leprosy as effector cells. Lepromatous
      patients present intense infiltrate of neutrophils in reactional (ENL) lesions.
      Circulating PMN of nonreactional patients, healthy donors, and reactional
      patients were purified and analyzed in vitro. The study confirmed the short
      lifespan of these cells in culture with progressive changes characteristic of
      apoptosis. Apoptosis was greatly accelerated in ENL patients as shown by cellular
      morphology, later confirmed by qualitative and quantitative analysis of
      fragmented DNA. It was observed that neutrophils stimulated with
      lipopolysaccharide, Mycobacterium leprae, and lipoarabinomannan secrete
      interleukin-8 and tumor necrosis factor alpha (TNF-alpha). Thalidomide, a drug
      known to inhibit TNF-alpha synthesis on monocytes, also exerted an inhibitory
      effect on TNF-alpha secretion in neutrophils. These data suggest that PMN can
      participate in the regulation of the immune response in leprosy and can
      contribute to the amplification of TNF-alpha production at the site of ENL
      lesion.

PMID- 10080542
TI  - Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their
      association with Grb2 and Shc in Baf3/Flt3 cells.
AB  - Flt3 ligand (FL) is an early-acting potent co-stimulatory cytokine that regulates
      proliferation and differentiation of a number of blood cell lineages. Its
      receptor Flt3/Flk2 belongs to class III receptor tyrosine kinases that also
      include the receptors for colony-stimulating factor 1, Steel factor, and platelet
      derived growth factor. Using CSF-1 receptor/Flt3 chimeras, two groups have
      characterized some of the post-receptor signaling events and substrate
      specificity of murine Flt3 receptor. However, there are few studies on the
      signaling pathway through human Flt3. We examined human Flt3 signaling pathways
      in a murine IL-3-dependent hematopoietic cell line Baf3, which stably expresses
      full-length human Flt3 receptor. This subline proliferates in response to human
      FL. Like the chimeric murine Flt3, human Flt3 undergoes autophosphorylation,
      associates with Grb2, and leads to tyrosine phosphorylation of Shc on ligand
      binding. We found that SHP-2, but not SHP-1, is tyrosine-phosphorylated by FL
      stimulation. SHP-2 does not associate with Flt3, but binds directly to Grb2. SHIP
      is also tyrosine-phosphorylated and associates with Shc after FL simulation. We
      further examined the downstream signaling pathway. FL transiently activates MAP
      kinase. This activation could be blocked by PD98059, a specific MEK inhibitor.
      PD98059 also blocked cell proliferation in response to FL. These results
      demonstrate that SHP-2 and SHIP are important components in the human Flt3
      signaling pathway and suggest that SHP-2 and SHIP, by forming complexes with
      adapter proteins Grb2 and Shc, may modulate MAP kinase activation, which may be
      necessary for the mitogenic signaling of Flt3.

PMID- 10080543
TI  - Relationships between phosphatidic acid and cyclic nucleotide phosphodiesterases
      in activated human blood mononuclear cells.
AB  - We have previously shown that mitogenic activation of human PBMC rapidly
      increases both the intracellular phosphatidic acid (PA) level and cyclic
      nucleotide phosphodiesterase (PDE) activity, with time-course responses,
      suggesting a causative relationship between the two events. PA also directly
      stimulated cAMP-PDE activity in acellular systems. Thus the mitogenic properties
      of PA night be due to its ability to lower the level of cAMP, a negative effector
      of lymphocyte activation, through PDE activation. In this study, human PBMC were
      stimulated either with the mitogenic lectin ConA, the anti-CD3 mAb OKT3, or the
      phorbol ester TPA. All three agonists increased the radiolabeled PA level and the
      PA mass in treated cells and simultaneously increased cytosolic and particulate
      cAMP- and cGMP-PDE activities, with significant positive correlations between PA
      accumulation and PDE activities. Furthermore, the ConA-induced PDE activation was
      dose-dependently reduced by treatment of PBMC with the diacylglycerol-kinase
      inhibitor R59022. This compound also dose-dependently lowered the PA level and
      inhibited the proliferative response to ConA. In addition, TPA-induced PDE
      activation was totally abolished by ethanol, which strongly reduced PA
      accumulation in response to the phorbol ester. These data suggest that PA
      increase may be linked to mitogen-induced PDE activation. Experiments performed
      in the presence of rolipram indicated that ConA and TPA stimulated both the
      rolipram-sensitive PDE4 and the rolipram-insensitive PDE activities, OKT3 being
      more active on PDE4. All three agonists stimulated the cGMP-specific PDE5. These
      results suggest that PA is an important component of the mechanisms that maintain
      a low level of cyclic nucleotides, which is a prerequisite for an optimal
      lymphoproliferative response.

PMID- 10080544
TI  - Lineage-specific activation of STAT3 by interferon-gamma in human neutrophils.
AB  - Binding of interferon-gamma (IFN-gamma) to its heterodimeric receptor induces
      activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine
      phosphorylation of STAT1alpha. Selective activation of STAT1alpha at the IFN
      gamma receptor is achieved by specific interaction between a cytosolic tyrosine
      motif including Y440 in the IFN-gamma receptor alpha-chain and the SH2 domain of
      STAT1alpha. We demonstrate that, in addition to STAT1alpha, STAT3 is also
      activated by IFN-gamma in human neutrophils. The activation of STAT3 was not
      found in human eosinophils, monocytes, and HL-60 cells, although the STAT3
      protein was expressed in these cells. The cell type-specific activation of STAT3
      by IFN-gamma was also observed in neutrophils that are differentiated in vitro
      from human CD34+ hematopoietic stem cells. These results indicate that a single
      cytokine receptor can activate different STAT family members in a cell-specific
      manner, which might result in cell-specific gene transcription.

PMID- 10080545
TI  - Co-expression of several human syntaxin genes in neutrophils and differentiating
      HL-60 cells: variant isoforms and detection of syntaxin 1.
AB  - Syntaxins are major components of vesicle trafficking and their pattern of
      expression depends on the cell type. Using reverse transcriptase-polymerase chain
      reaction (RT-PCR), cloning, and sequencing techniques, we have found that human
      neutrophils and neutrophil-differentiated HL-60 cells co-express syntaxins 1A, 3,
      4, 5, 6, 7, 9, 11, and 16. These genes are also expressed in human peripheral
      blood lymphocytes and SH-SY5Y neuroblastoma cells, which, unlike neutrophils,
      also expressed syntaxin 10. We have identified two isoforms of syntaxin 3.
      Syntaxin 3A, similar to the previously reported syntaxin 3, and the novel isoform
      syntaxin 3B, which is identical to syntaxin 3A but lacks 37 amino acid residues
      at the carboxy-terminal region. Syntaxin 1 was mainly located to neutrophil
      granule membranes by confocal microscopy and by immunoblotting of subcellular
      fractions. These data indicate that syntaxin 1 cannot be considered specific to
      neural tissues. The level of expression of syntaxins 3, 4, 6, and 11 was
      increased during neutrophil differentiation of HL-60 cells, whereas that of
      syntaxins 1A, 5, 9, and 16 was unchanged. Syntaxin 7 was not expressed in
      undifferentiated HL-60 cells, but its expression was induced on neutrophil
      differentiation. The expression of several syntaxin genes in human neutrophils
      could be related to the high secretory capacity of these cells as well as to the
      presence of different cytoplasmic granules with distinct exocytic capabilities.

PMID- 10080546
TI  - Acute and chronic responses to psychological trauma: where do we go from here?

PMID- 10080547
TI  - Images in neuroscience. Brain development, XI: sexual dimorphism.

PMID- 10080548
TI  - Posttraumatic stress disorder and identification in disaster workers.
AB  - OBJECTIVE: Disaster workers who work with deceased victims are at increased risk
      of posttraumatic stress disorder (PTSD). Identification with the deceased has
      been proposed as one of the mechanisms in this stress-illness relationship. To
      examine this hypothesis, this study investigated three types of identification
      with the dead in a group of disaster workers: identification with the deceased as
      oneself, identification with the deceased as a friend, and identification with
      the deceased as a family member. METHOD: Fifty-four volunteer disaster workers
      who worked with the dead following an explosion on the USS Iowa naval ship were
      assessed 1, 4, and 13 months after the disaster. PTSD symptoms (measured with the
      DSMPTSD-IV scale), intrusive and avoidant disaster-related symptoms (measured
      with the Impact of Event Scale), somatization and general distress (measured with
      the SCL-90-R), and health care utilization were assessed. RESULTS: Disaster
      workers who reported identification with the deceased as a friend were more
      likely than those who did not to have PTSD, more intrusive and avoidant symptoms,
      and greater levels of other posttraumatic symptoms including somatization.
      Disaster workers who reported identification with the deceased as a family member
      had greater intrusive symptoms 1 month after the disaster than those who did not.
      There were no differences between those who did and did not identify with the
      deceased as self. Health care utilization was not associated with identification.
      CONCLUSIONS: Identification with the deceased is a risk factor for PTSD and
      posttraumatic symptoms in disaster workers exposed to the dead. Identification
      with the dead as a friend is specifically associated with higher risk for these
      workers.

PMID- 10080549
TI  - Acute stress disorder and posttraumatic stress disorder in victims of violent
      crime.
AB  - OBJECTIVE: In a group of crime victims recruited from the community, the authors
      investigated the ability of both a diagnosis of acute stress disorder and its
      component symptoms to predict posttraumatic stress disorder (PTSD) at 6 months.
      METHOD: A mixed-sex group of 157 victims of violent assaults were interviewed
      within 1 month of the crime. At 6-month follow-up 88% were reinterviewed by
      telephone and completed further assessments generating estimates of the
      prevalence of PTSD. RESULTS: The rate of acute stress disorder was 19%, and the
      rate of subsequent PTSD was 20%. Symptom clusters based on the DSM-IV criteria
      for acute stress disorder were moderately strongly interrelated. All symptom
      clusters predicted subsequent PTSD, but not as well as an overall diagnosis of
      acute stress disorder, which correctly classified 83% of the group. Similar
      predictive power could be achieved by classifying the group according to the
      presence or absence of at least three reexperiencing or arousal symptoms.
      Logistic regression indicated that both a diagnosis of acute stress disorder and
      high levels of reexperiencing or arousal symptoms made independent contributions
      to predicting PTSD. CONCLUSIONS: This exploratory study provides evidence for the
      internal coherence of the new acute stress disorder diagnosis and for the symptom
      thresholds proposed in DSM-IV. As predicted, acute stress disorder was a strong
      predictor of later PTSD, but similar predictive power may be possible by using
      simpler criteria.

PMID- 10080550
TI  - Acute stress response and posttraumatic stress disorder in traffic accident
      victims: a one-year prospective, follow-up study.
AB  - OBJECTIVE: This study was designed to assess the natural course of posttraumatic
      symptoms formation, as well as the degree to which acute stress reactions predict
      later posttraumatic stress disorder (PTSD) in injured traffic accident victims.
      METHOD: A prospective, 1-year follow-up study was carried out on 74 injured
      traffic accident victims and a comparison group of 19 patients who were
      hospitalized for elective orthopedic surgery. Participants were interviewed
      within the first week following the accident, and follow-up interviews were
      performed 1, 3, 6, and 12 months after the accident. At 12 months, a structured
      clinical interview was administered to determine a formal DSM-III-R diagnosis of
      PTSD. RESULTS: Twenty-four (32%) of the 74 traffic accident victims, but none of
      the 19 comparison subjects, met DSM-III-R criteria for PTSD at 1 year. Traffic
      accident victims who developed PTSD had higher levels of premorbid and comorbid
      psychopathology. Levels of posttraumatic symptoms were significantly higher from
      the outset in the subjects who developed PTSD and worsened progressively over the
      first 3 months, in contrast to subjects without PTSD, who manifested gradual
      amelioration of symptoms during this time. Existence of posttraumatic symptoms
      immediately after the accident was a better predictor of later PTSD than was
      accident or injury severity. CONCLUSIONS: In this study, a significant portion of
      injured traffic accident victims manifested PTSD 1 year after the event. The
      development of PTSD at 1 year can be predicted as early as 1 week after the
      accident on the basis of the existence and severity of early PTSD-related
      symptoms. However, the first 3 months following the accident appear to be the
      critical period for the development of PTSD.

PMID- 10080551
TI  - Rate of psychiatric illness 1 year after traumatic brain injury.
AB  - OBJECTIVE: Neurobehavioral symptoms are not uncommon after a traumatic brain
      injury. However, psychiatric syndromes per se have rarely been studied in
      patients with such an injury. The purpose of this study was to evaluate the type
      and extent of psychiatric syndromes in patients with traumatic brain injury.
      METHOD: One hundred ninety-six hospitalized adults were studied 1 year after a
      traumatic brain injury with the use of a two-stage psychiatric diagnostic
      procedure. Psychiatric diagnoses were made according to ICD-10 criteria on the
      basis of data from the Schedules for Clinical Assessment in Neuropsychiatry
      interview. RESULTS: Of 164 patients interviewed, 30 (18.3%) had an ICD-10
      diagnosis of a psychiatric illness. Among the 120 patients who were 18-64 years
      old, 21.7% had a psychiatric illness, compared with 16.4% in a study of the
      general population. A depressive illness was present in 13.9% of the traumatic
      brain injury patients, compared with 2.1% of the general population, and panic
      disorder was present in 9.0%, compared with 0.8% of the general population.
      CONCLUSIONS: In comparison with the general population, a higher proportion of
      adult patients had developed psychiatric illnesses 1 year after a traumatic brain
      injury; the rates of depressive episode and panic disorder were significantly
      higher in the study group. A history of psychiatric illness, an unfavorable
      global outcome according to the Glasgow Outcome Scale, a lower score on the Mini
      Mental State examination, and fewer years of formal education seemed to be
      important risk factors in the development of a psychiatric illness. Compensation
      claims, however, were not associated with the rate of psychiatric illness.

PMID- 10080552
TI  - Childhood trauma and perceived parental dysfunction in the etiology of
      dissociative symptoms in psychiatric inpatients.
AB  - OBJECTIVE: Research on the etiology of dissociation in adults has focused
      primarily on childhood sexual abuse. The role of co-occurring childhood stressors
      and of more chronic adverse conditions such as neglect is less clear. This study
      examined the level of dissociation in relation to childhood trauma
      (sexual/physical abuse, witnessing interparental violence), early separation from
      a parent, and perceived parental dysfunction. METHOD: One hundred sixty
      inpatients consecutively admitted to a general psychiatric hospital were
      administered the Dissociative Experiences Scale and the Structured Trauma
      Interview. RESULTS: The mean Dissociative Experiences Scale score was 17.4; 18.0%
      of the patients scored beyond 30. Early separation was reported by 26.4% of the
      patients; 30.1% had witnessed interparental violence; 23.6% reported physical
      abuse; 34.6% reported sexual abuse; 11.7% reported rape before age 16; and 42.1%
      reported sexual and/or physical abuse. The level of dissociation was primarily
      related to reported overwhelming childhood experiences (sexual and physical
      abuse). When sexual abuse was severe (involving penetration, several
      perpetrators, lasting more than 1 year), dissociative symptoms were even more
      prominent. Highest dissociation levels were found in patients reporting
      cumulative sexual trauma (intrafamilial and extrafamilial) or both sexual and
      physical abuse. In particular, maternal dysfunction was related to the level of
      dissociation. With control for gender and age, stepwise multiple regression
      analysis indicated that the severity of dissociative symptoms was best predicted
      by reported sexual abuse, physical abuse, and maternal dysfunction. CONCLUSIONS:
      These findings indicate that dissociation, although trauma-related, is neglect
      related as well. This implies the importance of object relations and attachment
      in the diagnosis and treatment of patients with dissociative disorders.

PMID- 10080553
TI  - Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron
      emission tomography study.
AB  - OBJECTIVE: This study explored the neural circuitry used during recall of
      unstructured verbal material in schizophrenic patients and healthy volunteer
      subjects. METHOD: The subjects were 13 healthy volunteers and 14 schizophrenic
      patients. All patients were free of medication, and all subjects were right
      handed. Two experimental cognitive conditions were used: recall of novel and
      practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning
      Test). Both active recall tasks were compared with an eyes-closed resting
      baseline condition. A nonparametric randomization test was used to determine
      within- and between-group differences in regional cerebral blood flow. RESULTS:
      Performance on both the practiced and novel memory tasks was nonsignificantly
      different in the patients and control subjects. During the novel memory task, the
      patients showed decreased flow in the right anterior cingulate, right thalamus,
      and bilateral cerebellum (left greater than right) relative to the control
      subjects. When recalling the practiced word lists, the patients showed decreased
      flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex,
      left supplementary motor area, left thalamus, left cerebellar regions, anterior
      vermis, and right cuneus. CONCLUSIONS: Patients with schizophrenia fail to
      activate cortical-cerebellar-thalamic-cortical circuitry during recall of both
      well-learned and novel word lists.

PMID- 10080554
TI  - Selective speech perception alterations in schizophrenic patients reporting
      hallucinated "voices".
AB  - OBJECTIVE: The authors tested a model of hallucinated "voices" based on a neural
      network computer simulation of disordered speech perception. METHOD: Twenty-four
      patients with schizophrenia spectrum disorders who reported hallucinated voices
      were compared with 21 patients with schizophrenia spectrum disorders who did not
      report voices and 26 normal subjects. Narrative speech perception was assessed
      through use of a masked speech tracking task with three levels of superimposed
      phonetic noise. A sentence repetition task was used to assess grammar-dependent
      verbal working memory, and an auditory continuous performance task was used to
      assess nonlanguage attention. RESULTS: Masked speech tracking task and sentence
      repetition performance by hallucinating patients was impaired relative to both
      nonhallucinating patients and normal subjects. Although both hallucinating and
      nonhallucinating patients demonstrated auditory attention impairments when
      compared to normal subjects, the two patient groups did not differ with respect
      to these variables. CONCLUSIONS: Results support the hypothesis that hallucinated
      voices in schizophrenia arise from disrupted speech perception and verbal working
      memory systems rather than from nonlanguage cognitive or attentional deficits.

PMID- 10080555
TI  - Symptoms and cognition as predictors of community functioning: a prospective
      analysis.
AB  - OBJECTIVE: It has been suggested that level of cognitive functioning as assessed
      by formal neurocognitive tests may be as important as, or even more important
      than, symptoms in predicting level of community functioning for patients with
      schizophrenia. The results of past prospective studies, when carefully examined,
      do not consistently support this hypothesis. In the current study, the authors
      used symptom and neurocognitive data to predict subsequent level of functioning
      in the community. METHOD: Neurocognitive and symptom data collected as part of an
      earlier study were used to predict the community functioning of 50 patients with
      a diagnosis of schizophrenia. Using the Life Skills Profile, staff of a community
      mental health program assessed community functioning while blind to the earlier
      symptom ratings and neurocognitive performance. RESULTS: Symptoms were more
      predictive of community functioning than were neurocognitive measures.
      Disorganization symptoms were generally more predictive of community functioning
      than was either psychomotor poverty or reality distortion. CONCLUSIONS: The
      results of this study and of previous longitudinal studies suggest the importance
      of using symptom levels after optimal treatment, rather than symptoms during
      acute episodes, as predictors of community functioning. They also indicate the
      need to evaluate the effects of treatment on disorganization as a separable
      dimension of symptoms.

PMID- 10080556
TI  - Empirical validation of primary negative symptoms: independence from effects of
      medication and psychosis.
AB  - OBJECTIVE: Recent studies of negative symptoms in schizophrenia-specifically,
      those involving the deficit syndrome-have focused on uncovering the symptoms that
      are primary to the disease rather than secondary to the psychotic process. One of
      the foremost concerns in this effort is establishing whether the negative
      symptoms observed are the result of medication effects. METHOD: This study used
      negative symptom ratings obtained in a drug withdrawal paradigm to compare
      symptom profiles in the same schizophrenic patients when they were on and off
      antipsychotic drug treatment. The study group consisted of 93 physically healthy
      male patients with DSM-III-R-defined schizophrenia. Principal components analysis
      was performed on negative symptom data obtained separately during haloperidol
      treatment and again when the patients were drug free to determine whether there
      were meaningful factor scores that were consistent across medication conditions.
      Drug withdrawal effects on negative symptom factors were then tested for
      associations with secondary sources of variance including extrapyramidal side
      effects, anxiety/depression, and psychosis. RESULTS: Two factors, termed
      affective flattening and diminished motivation, exhibited similar loadings when
      the patients were both on and off medication. Changes in motivation were
      associated with changes in anxiety/depression and psychosis, while changes in
      affective flattening were associated with changes in extrapyramidal side effects.
      CONCLUSIONS: The documented secondary sources of negative symptoms are related to
      different and distinct aspects of negative symptoms; this finding will aid in the
      identification of primary negative symptoms.

PMID- 10080557
TI  - Comparative effectiveness of fluphenazine decanoate injections every 2 weeks
      versus every 6 weeks.
AB  - OBJECTIVE: Dose reduction strategies for the maintenance treatment of
      schizophrenia are designed to maintain the benefits of antipsychotic drug therapy
      while reducing risks. Previous strategies with decanoate preparations have been
      based on the use of lower doses per injection to achieve dose reduction; these
      strategies have achieved dose reduction but have resulted in some increase in
      symptoms. The authors tested a new dose reduction approach: increasing the
      interval between injections during intramuscular decanoate antipsychotic
      treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective
      disorder were randomly assigned to receive 25 mg of fluphenazine decanoate
      intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double
      blind design. RESULTS: The two dose regimens did not differ significantly in
      relapse, symptom, or side effect measures. The every-6-weeks regimen was
      associated with a significant reduction in total antipsychotic exposure.
      CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may
      increase compliance and improve patients' comfort as well as decrease cumulative
      antipsychotic exposure, without increasing relapse rates or symptoms.

PMID- 10080558
TI  - Placebo-controlled study of the D4/5-HT2A antagonist fananserin in the treatment
      of schizophrenia.
AB  - OBJECTIVE: The authors' objective was to assess the potential efficacy of
      fananserin (RP62203), a potent antagonist at the D4 and serotonin2A (5-HT2A)
      receptors, on symptoms of schizophrenia. METHOD: A double-blind, placebo
      controlled study was conducted in 97 patients. Doses of fananserin reached 250 mg
      b.i.d. over 28 days, starting with an 8-day escalation. Most of the patients were
      men with paranoid schizophrenia; they were approximately 38 years old. The
      primary outcome measure was the total Positive and Negative Syndrome Scale score.
      The patients' mean score on the Positive and Negative Syndrome Scale at entry was
      91.8 (SD=16.5). A low dropout rate was observed in both groups of patients (19
      [30%] of those given fananserin and nine [27%] of those given placebo). RESULTS:
      The total Positive and Negative Syndrome Scale score of the patients given
      fananserin decreased at endpoint by a mean of 4.2 points (SD=15.4); the score of
      the patients given placebo decreased by 6.7 points (SD=19.6). No differences
      between treatments were found on secondary measures such as the Clinical Global
      Impression, Positive and Negative Syndrome Scale subscores or individual items,
      and Brief Psychiatric Rating Scale total score. The patients' extrapyramidal
      symptoms did not worsen during the trial, but the patients given fananserin had
      an increase in akathisia. The safety profile was good in both groups of patients.
      CONCLUSIONS: The results of this study do not support the prediction that a
      selective D4 antagonist associated with strong 5-HT2A antagonism will exhibit an
      antipsychotic effect.

PMID- 10080559
TI  - Phenomenology of mania: evidence for distinct depressed, dysphoric, and euphoric
      presentations.
AB  - OBJECTIVE: A substantial number of manic episodes include conspicuous depressive
      symptoms. Manic episodes have been clinically classified a posteriori using
      preset criteria. The aim of this study was to investigate the possibility that
      there might be a natural division of manic episodes into clinical types. METHOD:
      One hundred and five inpatients met Research Diagnostic Criteria and DSM-III-R
      criteria for manic episodes and were rated before institution of pharmacological
      treatment. The authors conducted a factor analysis of 37 behavior rating items
      from the Schedule for Affective Disorders and Schizophrenia. The resulting
      factors were used as independent variables in a cluster analysis of the patients.
      RESULTS: This analysis revealed four factors corresponding to manic activation,
      depressed state, sleep disturbance, and irritability/paranoia. Cluster analysis
      separated the patients into two groups. One included patients with major
      depressive disorder and mania. Blind, a priori clinical classification into
      classic and mixed mania (mania plus depression) showed that all of the patients
      in the depressed cluster, and about 40% of those in the nondepressed cluster,
      were in a mixed state according to clinical criteria. Comparison of the
      clinically mixed and nonmixed patients in the nondepressed cluster revealed that
      the mixed patients in that cluster had higher scores for items related to anger,
      worry, dysphoria, and irritability. CONCLUSIONS: These data suggest that manic
      episodes can be naturalistically classified as classic (predominately euphoric),
      dysphoric, or depressed.

PMID- 10080560
TI  - Characteristics of depressed patients who report childhood sexual abuse.
AB  - OBJECTIVE: Depressed patients who had and had not been exposed to childhood
      sexual abuse were studied to determine differences in severity of depressed mood,
      lifetime histories of anxiety and depression, childhood environment, and
      disordered personality function. METHOD: Data were obtained from 269 inpatients
      and outpatients with major depression (171 women and 98 men) by means of
      structured clinical interviews and self-report questionnaires. RESULTS: Forty-six
      of the 269 patients reported childhood sexual abuse; 40 of these were women.
      These 40 women were compared with the 131 who did not report childhood sexual
      abuse. The patients who experienced abuse did not differ from those who had not
      on psychiatrist-rated mood severity estimates, but they did have higher self
      report depression scores. They also evidenced more self-destructive behavior,
      more personality dysfunction, and more overall adversity in their childhood
      environment. Childhood sexual abuse status was associated with more borderline
      personality characteristics independently of other negative aspects of the
      patients' earlier parenting. Childhood sexual abuse status was linked strongly to
      adult self-destructiveness, as was early exposure to maternal indifference.
      CONCLUSIONS: Multivariate analyses suggest that depression is unlikely to be a
      direct consequence of childhood sexual abuse. Childhood sexual abuse appears to
      be associated with a greater chance of having experienced a broadly dysfunctional
      childhood home environment, a greater chance of having a borderline personality
      style, and, in turn, a greater chance of experiencing depression in adulthood.

PMID- 10080561
TI  - Neuropsychological functioning and MRI signal hyperintensities in geriatric
      depression.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      signal hyperintensities--a probable marker of underlying pathology--on T2
      weighted magnetic resonance brain scans and neuropsychological test findings in
      elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R
      diagnosis of major depression (N=41) and normal elderly comparison subjects
      (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal
      hyperintensities in periventricular, deep white matter, and subcortical gray
      matter. Hard copies of scans were rated in random order by research psychiatrists
      blind to diagnosis; the modified Fazekas hyperintensity rating scale was used.
      Cognitive performance was independently assessed with a comprehensive
      neuropsychological battery. Clinical and demographic differences between groups
      were assessed by t tests and chi-square analysis. Relationships between
      neuropsychological performance and diagnosis and hyperintensities and their
      interaction were analyzed by using analysis of covariance, with adjustment for
      age and education. RESULTS: Elderly depressed subjects manifested poorer
      cognitive performance on several tests than normal comparison subjects. A
      significant interaction between hyperintensity location/severity and
      presence/absence of depression on cognitive performance was found: depressed
      patients with moderate-to-severe deep white matter hyperintensities demonstrated
      worse performance on general and delayed recall memory indices, executive
      functioning and language testing than depressed patients without such lesions and
      normal elderly subjects with or without deep white matter changes. CONCLUSIONS:
      Findings validate cognitive performance decrements in geriatric depression and
      suggest possible neuroanatomic vulnerabilities to developing particular
      neuropsychological dysfunction in depressed subjects.

PMID- 10080562
TI  - Practice patterns of international and U.S. medical graduate psychiatrists.
AB  - OBJECTIVE: The practice patterns of international medical graduate (IMG) and U.S.
      medical graduate (USMG) psychiatrists were compared. METHOD: Using data from the
      1996 National Survey of Psychiatric Practice, the authors compared IMGs and USMGs
      in terms of demographic characteristics, practice settings, patients' clinical
      characteristics, and sources of reimbursement. RESULTS: The IMGs surveyed tended
      to be older than USMGs, included a higher proportion of women, and were more
      racially heterogeneous. They worked longer hours, worked more frequently in the
      public sector, and treated a higher proportion of patients with psychotic
      disorders. The IMGs also received a higher percentage of their income than USMGs
      from Medicaid and Medicare, whereas the reverse was true of self-payment. Most of
      these differences remained significant after psychiatrist's age, gender, race,
      board certification, and work setting were controlled for. CONCLUSIONS: IMG and
      USMG psychiatrists have different practice patterns. Policies that substantially
      decrease the number of IMG psychiatrists may adversely affect the availability of
      psychiatrists to treat minorities and other underserved populations.

PMID- 10080563
TI  - Trends in office-based psychiatric practice.
AB  - OBJECTIVE: The authors examine trends in the composition and duration of visits
      to psychiatrists in office-based psychiatric practice. METHOD: An analysis was
      performed of physician-reported data from the 1985 and 1995 National Ambulatory
      Medical Care Surveys focusing on visits to physicians specializing in psychiatry.
      Secular changes in visit characteristics were assessed, and mean visit durations
      were determined for selected sociodemographic and clinical groups. RESULTS: In
      the decade between 1985 and 1995, visits in office-based psychiatry became
      shorter, less often included psychotherapy, and more often included a medication
      prescription. The proportion of visits that were 10 minutes or less in length
      increased. A shortening in visit duration was most evident for younger patients,
      privately insured patients, and patients who were not prescribed a psychotropic
      medication. In the 1995 survey, 6.8% of the psychiatric visits included patient
      contact with another health care professional. CONCLUSIONS: Changing financial
      arrangements and new pharmacologic treatments may have contributed to these
      changes in practice style.

PMID- 10080564
TI  - Evaluating and treating violent adolescents in the managed care era.

PMID- 10080566
TI  - Improved cognition in Alzheimer's disease with short-term D-cycloserine
      treatment.
AB  - OBJECTIVE: Glutamatergic neurotransmission is important for memory and cognition
      and is severely affected in Alzheimer's disease. D-Cycloserine exhibits partial
      agonist activity at the glycine site of N-methyl-D-aspartate subtype glutamate
      receptor, facilitating activation of the receptor and improving cognition and
      memory. METHOD: Seventeen patients with Alzheimer's disease received a three
      phase, double-blind, placebo-controlled trial of 50 mg and 100 mg/day of D
      cycloserine. RESULTS: D-Cycloserine was associated with significant improvement
      in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale
      (improvement of 3.0 points) when given at a dose of 100 mg/day. CONCLUSIONS: D
      Cycloserine has cognitive benefits for patients with Alzheimer's disease.

PMID- 10080567
TI  - Association between brain functional failure and dementia severity in Alzheimer's
      disease: resting versus stimulation PET study.
AB  - OBJECTIVE: This study tested the hypothesis that regional cerebral glucose
      metabolism during neuronal activation is a more sensitive index of neuronal
      dysfunction and clinical severity in Alzheimer's disease than is glucose
      metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients
      with a wide range of Mattis Dementia Rating Scale scores (23-128). By using
      positron emission tomography, absolute glucose metabolism was measured in the
      parietal, occipital (visual areas), and temporal (auditory areas) cortical
      regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In
      the parietal cortex, glucose metabolism correlated with dementia severity in both
      conditions. In contrast, in the relatively preserved visual and auditory cortical
      regions, glucose metabolism predicted dementia severity during stimulation but
      not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose
      metabolism during stimulation is a more sensitive index of the
      functional/metabolic failure of neuronal systems than is metabolism at rest.

PMID- 10080568
TI  - Multiple anxiety disorder comorbidity in patients with mood spectrum disorders
      with psychotic features.
AB  - OBJECTIVE: The authors investigated frequencies and clinical correlates of
      multiple associations of panic disorder, obsessive-compulsive disorder (OCD), and
      social phobia in patients with severe mood disorders. METHOD: Subjects were 77
      consecutively hospitalized adults with psychotic symptoms and with a diagnosis of
      bipolar I disorder, major depression, or schizoaffective disorder, bipolar type.
      Principal diagnosis and comorbidity were assessed by the Structured Clinical
      Interview for DSM-III-R-Patient Version. RESULTS: Of the entire cohort, 33.8% had
      a single anxiety disorder and 14.3% had two or three comorbid diagnoses. Patients
      with multiple comorbidity had significantly higher scores on the Brief
      Psychiatric Rating Scale and SCL-90 and abused stimulants more frequently than
      did those without anxiety disorders. CONCLUSIONS: Multiple associations of panic
      disorder, OCD, and social phobia are not rare among patients with affective
      psychoses and are likely to be associated with more severe psychopathology than
      is found in patients without anxiety disorders.

PMID- 10080569
TI  - Depressive symptoms and health costs in older medical patients.
AB  - OBJECTIVE: The authors assessed the association between depressive symptoms and
      health costs for a national Veterans Administration (VA) sample. METHOD: The Rand
      Depression Index was administered to 1,316 medical or surgical inpatients over
      the age of 60 at nine VA hospitals. Scores were merged with utilization,
      demographic, and hospital data from national VA inpatient and outpatient files.
      RESULTS: Medical costs for respondents with the highest quartile of symptoms were
      approximately $3,200-or 50%-greater than medical costs for those in the least
      symptomatic quartile. Depressive symptoms were not associated with any
      statistically significant mental health expenditures. CONCLUSIONS: The study
      extends previous reports of the high medical costs associated with depressive
      disorders to an older, public sector population. The mechanisms underlying
      increased medical costs associated with depressive symptoms, while the subject of
      much speculation in the literature, still remain largely unknown.

PMID- 10080570
TI  - Gender difference in the prevalence of clinical depression: the role played by
      depression associated with somatic symptoms.
AB  - OBJECTIVE: This study tested the hypothesis that female subjects may exhibit a
      higher prevalence than male subjects of depression associated with somatic
      symptoms but not a higher prevalence of depression not associated with these
      other symptoms. METHOD: The author reanalyzed research interview data on major
      depression from the National Comorbidity Survey, dividing respondents into those
      who met overall criteria for major depression and exhibited fatigue and appetite
      and sleep disturbance ("somatic depression") and those who met overall criteria
      but did not exhibit these somatic criteria ("pure depression"). RESULTS: Female
      subjects exhibited a higher prevalence than male subjects of somatic depression
      but not a higher prevalence of pure depression. Somatic depression was associated
      with a high prevalence of anxiety disorder and, among female subjects, with body
      aches and onset of depression during early adolescence. CONCLUSIONS: The gender
      difference in depression may result from a difference in a specific subtype of
      anxious somatic depression.

PMID- 10080571
TI  - Assessing long-term effects of trauma: diagnosing symptoms of avoidance and
      numbing.
AB  - OBJECTIVE: This study compared the discovery of posttraumatic stress disorder
      (PTSD) symptoms by means of the Structured Clinical Interview for DSM-III-R
      (SCID) with a semistructured, psychodynamic clinical interview in a long-term
      follow-up of the survivors of the Buffalo Creek (W.Va.) flood. METHOD: Videotaped
      semistructured, psychodynamic clinical interviews of a small group of survivors
      (N=6) were compared with the results obtained in a prior group-level SCID
      investigation. RESULTS: Seventy-two percent of the total PTSD symptoms for the
      subjects studied were elicited exclusively by the psychodynamic clinical
      interview. PTSD cluster C symptoms of avoidance and numbing of general
      responsiveness were especially sensitive to discovery by this method.
      CONCLUSIONS: The psychodynamic clinical interview should be included in the
      design of studies that seek to investigate long-term effects of trauma, which are
      especially likely to be manifest in negative symptoms and subtle character
      change.

PMID- 10080572
TI  - Combination treatment with venlafaxine and bupropion.

PMID- 10080573
TI  - ECT therapy in PTSD.

PMID- 10080574
TI  - Treatment of Tourette's syndrome with delta-9-tetrahydrocannabinol.

PMID- 10080575
TI  - Neurosurgery for obsessive-compulsive disorder: problems with comorbidity.

PMID- 10080576
TI  - Persistent delirium tremens.

PMID- 10080577
TI  - Another explanation for the apparent discrimination against international medical
      graduates by residency programs.

PMID- 10080578
TI  - Cognitive deficits in adolescents with schizophrenia undergoing antipsychotic
      treatment.

PMID- 10080579
TI  - Paranoid schizophrenia--malingering or factitious disorder?

PMID- 10080580
TI  - Another perspective on "putting DSM-IV in perspective".

PMID- 10080581
TI  - Another perspective on "putting DSM-IV in perspective".

PMID- 10080582
TI  - Acute lymphoblastic leukemia in infants.

PMID- 10080583
TI  - Neoadjuvant chemotherapy, locally advanced breast cancer, and quality of life.

PMID- 10080584
TI  - Treatment outcome and prognostic factors for infants with acute lymphoblastic
      leukemia treated on two consecutive trials of the Children's Cancer Group.
AB  - PURPOSE: Infants represent a very poor risk group for acute lymphoblastic
      leukemia (ALL). We report treatment outcome for such patients treated with
      intensive therapy on consecutive Children's Cancer Group (CCG) protocols.
      PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL
      were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols.
      Postconsolidation therapy was more intensive on CCG-1883. On both studies,
      prophylactic treatment of the CNS included both high-dose systemic chemotherapy
      and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used
      in earlier studies. RESULTS: Most patients (>95%) achieved remission with
      induction therapy. The most frequent event was a marrow relapse (46 patients on
      CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE
      = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an
      improvement compared with a 22% (SE = 5.1%) event-free survival for historical
      controls. Four-year cumulative probabilities of any marrow relapse or an isolated
      CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50%
      (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE =
      3%) for the historical controls. Independent adverse prognostic factors were age
      less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow
      response to induction therapy, and presence of the translocation t(4;11).
      CONCLUSION: Outcome for infants on CCG-107 and CCG- 1883 improved, compared with
      historical controls. Marrow relapse remains the primary mode of failure. Isolated
      CNS relapse rates are low, indicating that intrathecal chemotherapy combined with
      very-high-dose systemic therapy provides adequate protection of the CNS. The
      overall unsatisfactory outcome observed for the infant ALL population warrants
      the future use of novel alternative therapies.

PMID- 10080585
TI  - Treatment of localized primary non-Hodgkin's lymphoma of bone in children: a
      Pediatric Oncology Group study.
AB  - PURPOSE: The treatment of primary lymphoma of bone (PLB) in children has
      traditionally included radiotherapy to the primary site; more recently, it has
      included systemic chemotherapy. Because of concern about the untoward effects of
      treatment in a disease that is curable, we attempted to determine whether
      radiotherapy can be safely excluded from treatment. PATIENTS AND METHODS: The
      results of three consecutive Pediatric Oncology Group (POG) studies were examined
      to determine the impact on outcome of radiotherapy as adjunctive treatment in
      children and adolescents receiving chemotherapy for early-stage primary lymphoma
      of bone. RESULTS: From 1983 to 1997, 31 patients with localized PLB were entered
      onto POG studies of early-stage non-Hodgkin's lymphoma (NHL). Between 1983 and
      1986, seven patients were treated with 8 months of chemotherapy with irradiation
      (XRT) of the primary site. After 1986, patients were treated without XRT; four
      received 8 months of chemotherapy, and 20 received 9 weeks of chemotherapy.
      Primary sites were the femur (nine), tibia (eight), mandible (five), mastoid
      (one), maxilla (one), zygomatic arch (one), rib (one), clavicle (one), scapula
      (one), ulna (one), talus (one), and calcaneous (one). Histologic classification
      revealed 21 cases of large cell lymphoma, five cases of lymphoblastic lymphoma,
      two cases of small, noncleaved-cell lymphoma, and three cases of NHL that could
      not be classified further. One patient relapsed at a distant site 22 months after
      completion of therapy. There have been no deaths. CONCLUSION: Localized PLB is
      curable in most children and adolescents with a 9-week chemotherapy regimen of
      modest intensity, and radiotherapy is an unnecessary adjunct.

PMID- 10080586
TI  - Clinical course of breast cancer patients with complete pathologic primary tumor
      and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy.
AB  - PURPOSE: To assess patient and tumor characteristics associated with a complete
      pathologic response (pCR) in both the breast and axillary lymph node specimens
      and the outcome of patients found to have a pCR after neoadjuvant chemotherapy
      for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred
      seventy-two LABC patients received treatment in two prospective neoadjuvant
      trials using four cycles of doxorubicin-containing chemotherapy. Patients had a
      total mastectomy with axillary dissection or segmental mastectomy and axillary
      dissection followed by four or more cycles of additional chemotherapy. Patients
      then received irradiation treatment of the chest-wall or breast and regional
      lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The
      initial nodal status, age, and stage distribution of patients with a pCR were not
      significantly different from those of patients with less than a pCR (P>.05).
      Patients with a pCR had initial tumors that were more likely to be estrogen
      receptor (ER)-negative (P<.01), and anaplastic (P = .01) but of smaller size
      (P<.01) than those of patients with less than a pCR. Upon multivariate analysis,
      the effects of ER status and nuclear grade were independent of initial tumor
      size. Sixteen percent of the patients in this study (n = 60) had a pathologic
      complete primary tumor response. Twelve percent of patients (n = 43) had no
      microscopic evidence of invasive cancer in their breast and axillary specimens. A
      pathologic complete primary tumor response was predictive of a complete axillary
      lymph node response (P<.01 ). The 5-year overall and disease-free survival rates
      were significantly higher in the group who had a pCR (89% and 87%, respectively)
      than in the group who had less than a pCR (64% and 58%, respectively; P<.01).
      CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the
      breast and axillary lymph nodes of invasive tumor before surgery. Patients with
      LABC who have a pCR in the breast and axillary nodes have a significantly
      improved disease-free survival rate. However, a pCR does not entirely eliminate
      recurrence. Further efforts should focus on elucidating the molecular mechanisms
      associated with this response.

PMID- 10080587
TI  - Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1
      assays to quantitate proliferation in breast cancer.
AB  - PURPOSE: To investigate the hypothesis that in vitro bromodeoxyuridine (BrDu)
      labeling might be superior to MIB-1 immunostaining for prognostic value, because
      it more selectively labels cells during the S phase. METHODS: Four hundred eighty
      six patients with breast cancers (59% lymph node-negative, 41% lymph node
      positive) surgically excised between 1988 and 1993 (median follow-up, 62 months)
      were evaluated for cellular proliferation using prospective in vitro BrDu uptake
      assays, retrospective mitotic indices, and MIB-1 labeling. RESULTS: MIB-1, BrDu
      labeling, and mitotic index-derived proliferation data were highly correlated.
      Each was similarly associated with most other markers of prognosis, although
      these relationships were not identical. By univariate analysis, nodal status was
      the most significant prognostic variable for all patients. Higher BrDu labeling
      index, MIB-1 immunolabeling, and mitotic index were also associated with
      shortened disease-free survival (DFS) and disease-specific survival for the
      entire patient group, as well as for node-negative patients. The association
      between cellular proliferation and survival was much weaker for node-positive
      patients. Multivariate models confirmed that nodal status, tumor size, and
      proliferation data predicted survival in all patients as well as those with node
      negative disease, although MIB-1 was somewhat more closely associated with
      outcome than mitotic index or in vitro BrDu data. For patients with T1NOMO
      disease (n = 172), the only significant predictors of DFS were proliferation rate
      (mitotic index or MIB-1) and tumor grade. CONCLUSIONS: Proliferation rate
      predicts recurrence and survival in breast cancer. This effect is more pronounced
      in node-negative patients. In vitro BrDu data are not superior to MIB-1 and
      mitotic counting.

PMID- 10080588
TI  - Randomized phase II study of BR96-doxorubicin conjugate in patients with
      metastatic breast cancer.
AB  - PURPOSE: BMS-182248-1 (BR96-doxorubicin immunoconjugate) is a chimeric
      human/mouse monoclonal antibody linked to approximately eight doxorubicin
      molecules. The antibody is directed against the Lewis-Y antigen, which is
      expressed on 75% of all breast cancers but is limited in expression on normal
      tissues. Preclinical xenograft models demonstrated significant antitumor
      activity, including cures. A randomized phase II design was chosen to estimate
      the activity of the BR96-doxorubicin conjugate in metastatic breast cancer in a
      study population with confirmed sensitivity to single-agent doxorubicin. PATIENTS
      AND METHODS: Patients with measurable metastatic breast cancer and
      immunohistochemical evidence of Lewis-Y expression on their tumor received either
      BR96-doxorubicin conjugate 700 mg/m2 IV over 24 hours or doxorubicin 60 mg/m2
      every 3 weeks. Patients were stratified on the basis of prior doxorubicin
      exposure, visceral disease, and institution. Cross-over to the opposite treatment
      arm was allowed with progressive or persistently stable disease. RESULTS: Twenty
      three patients who had received a median of one prior chemotherapy regimen were
      assessable. There was one partial response (7%) in 14 patients receiving the BR96
      doxorubicin conjugate and one complete response and three partial responses (44%)
      in nine assessable patients receiving doxorubicin. No patient experienced a
      clinically significant hypersensitivity reaction. The toxicities were
      significantly different between the two treatment groups, with the BR96
      doxorubicin conjugate group having limited hematologic toxicity, whereas
      gastrointestinal toxicities, including marked serum amylase and lipase
      elevations, nausea, and vomiting with gastritis, were prominent. CONCLUSION: The
      BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in
      metastatic breast cancer. The gastrointestinal toxicities likely represent
      binding of the agent to normal tissues expressing the target antigen and may have
      compromised the delivery of the immunoconjugate to the tumor sites.

PMID- 10080589
TI  - Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic
      breast cancer.
AB  - PURPOSE: Capecitabine is a novel, oral, selectively tumor-activated
      fluoropyrimidine carbamate. This large multicenter phase II trial tested the
      efficacy and safety of twice-daily oral capecitabine at 2,510 mg/m2/d given for 2
      weeks followed by a 1-week rest period and repeated in 3-week cycles, in patients
      with paclitaxel-refractory metastatic breast cancer. PATIENTS AND METHODS:
      Patients were to have received at least two but not more than three prior
      chemotherapeutic regimens, one of which had to have contained paclitaxel given
      for metastatic disease. One hundred sixty-three patients were entered onto the
      study at 25 centers, and 162 patients received capecitabine. One hundred thirty
      five patients had bidimensionally measurable disease, and 27 patients had
      assessable disease. RESULTS: The overall response rate was 20% (95% confidence
      interval, 14% to 28%). All responding patients were resistant to or had failed
      paclitaxel, and all had received an anthracycline. Three complete responses were
      seen, with complete response durations of 106, 109, and 194+ days. Median
      duration of response was 8.1 months, median survival time was 12.8 months, and
      the median time to disease progression was 93 days. The most common treatment
      related adverse events were hand-foot syndrome, diarrhea, nausea, vomiting, and
      fatigue. Diarrhea (14%) and hand-foot syndrome (10%) were the only treatment
      related adverse events that occurred with grade 3 or 4 intensity in more than 10%
      of patients. CONCLUSION: Capecitabine is an active drug in the treatment of
      paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity
      profile with the added advantage of being an oral drug administered at home.

PMID- 10080590
TI  - Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2.
AB  - PURPOSE: To determine the survival benefit and cost-effectiveness of screening
      Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. METHODS: We
      used a Markov model and Monte Carlo analysis to estimate the survival benefit and
      cost-effectiveness of screening for three specific mutations in a population in
      which their prevalence is 2.5% and the associated cancer risks are 56% for breast
      cancer and 16% for ovarian cancer. We assumed that the sensitivity and
      specificity of the test were 98% and 99%, respectively, that bilateral
      prophylactic oophorectomy would reduce ovarian cancer risk by 45%, and that
      bilateral prophylactic mastectomy would reduce breast cancer risk by 90%. We used
      Medicare payment data for treatment costs and Surveillance, Epidemiology, and End
      Results data for cancer survival. RESULTS: Our model suggests that genetic
      screening of this population could prolong average nondiscounted survival by 38
      days (95% probability interval, 22 to 57 days) for combined surgery, 33 days (95%
      probability interval, 18 to 43 days) for mastectomy, 11 days (95% probability
      interval, 4 to 25 days) for oophorectomy, and 6 days (95% probability interval, 3
      to 8 days) for surveillance. The respective cost-effectiveness ratios per life
      year saved, with a discount rate of 3%, are $20,717, $29,970, $72,780, and
      $134,273. CONCLUSION: In this Ashkenazi Jewish population, with a high prevalence
      of BRCA1/2 mutations, genetic screening may significantly increase average
      survival and, depending on costs and screening/treatment strategies, may be cost
      effective by the standards of accepted cancer screening tests. According to our
      model, screening is cost-effective only if all women who test positive undergo
      prophylactic surgery. These estimates require confirmation through prospective
      observational studies and clinical trials.

PMID- 10080591
TI  - Comparison of standard and CA-125 response criteria in patients with epithelial
      ovarian cancer treated with platinum or paclitaxel.
AB  - PURPOSE: To assess CA-125 as a measure of response in patients treated with
      paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with
      paclitaxel derived from four different trials and 625 patients treated with
      platinum from two trials were analyzed using precisely defined 50% and 75%
      reductions in CA-125. The standard and CA-125 response rates to paclitaxel and
      platinum were compared. In addition, we analyzed individual patient groups in
      which there was a difference in response according to the two response criteria.
      RESULTS: Patients with stable disease as determined by standard criteria who were
      treated with platinum and responded according to CA-125 criteria have an improved
      median progression-free survival compared with patients with stable disease who
      did not respond according to CA-125 criteria (10.6 v 4.8 months; P<.001).
      Standard and CA-125 response rates for patients treated with platinum (58.93% v
      61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very
      similar, as were rates of false-positive prediction of response by CA-125
      (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly
      improved progression-free survival compared with non-responders by both standard
      criteria (median progression-free survival, 6.8 v 2.5 months; P<.001) and CA-125
      criteria (median progression-free survival, 6.8 v 3.4 months; P<.001).
      CONCLUSION: Forassessing activity of therapy for ovarian cancer, these data show
      that precise 50% or 75% CA-125 response criteria are as sensitive as standard
      response criteria. We propose that they may be used as a measure of response in
      lieu of or in addition to standard response criteria in clinical trials involving
      epithelial ovarian cancer. Sensitivity is maintained whether patients are treated
      with platinum or paclitaxel.

PMID- 10080592
TI  - Phase II trial of gemcitabine in refractory germ cell tumors.
AB  - PURPOSE: This phase II study was designed to determine the toxicity and activity
      of single-agent gemcitabine in heavily pretreated patients with germ cell tumors.
      PATIENTS AND METHODS: From March 1996 through November 1997, 21 patients were
      enrolled onto a phase II study of gemcitabine 1,200 mg/m2, given on days 1, 8,
      and 15 every 4 weeks. One patient was unassessable because he never received any
      gemcitabine. Thirteen of 20 patients had received three prior regimens, and 13
      patients were platinum refractory (progression during or within 4 weeks of
      platinum treatment). There were five extragonadal cases and two patients with
      late relapse (relapse beyond 2 years). RESULTS: Gemcitabine was well tolerated.
      Only one patient had grade 3 or 4 nonhematologic toxicity (grade 3 nausea). Six
      of 20 patients had grade 3 leukopenia. There were no episodes of granulocytopenic
      fever, and no patient required platelet transfusion. Three (15%) of 20 patients
      achieved an objective response, including one complete remission. Three
      additional patients had a minor radiographic or serologic response. CONCLUSION:
      Gemcitabine had definite activity in this heavily pretreated germ cell tumor
      patient population.

PMID- 10080593
TI  - Gemcitabine in patients with relapsed or cisplatin-refractory testicular cancer.
AB  - PURPOSE: Despite generally high cure rates in patients with metastatic testicular
      germ cell tumors, patients with incomplete response to cisplatin-based first-line
      therapy or with relapsed disease after high-dose salvage chemotherapy have a very
      poor prognosis. This phase II study evaluates the use of gemcitabine in patients
      with intensively pretreated or cisplatin-refractory testicular germ cell cancers.
      PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled;
      31 patients were fully assessable. All patients had metastatic nonseminomatous
      germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients
      (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median
      number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%)
      had received high-dose chemotherapy with autologous stem-cell transplantation,
      and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients
      (54%) were considered refractory or absolutely refractory to chemotherapy.
      RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine,
      11 patients (35%) displayed no change, and 14 patients (45%) had disease
      progression. The median time to treatment failure was 4 months (range, 2 to 9+
      months), and the median survival was 6 months (range, 2 to 23 months). Patients
      received a median of six gemcitabine applications. Ten patients (32%) required
      dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia
      occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients
      (22%). One case of severe sepsis was observed. CONCLUSION: Gemcitabine displays
      antitumor activity in intensively pretreated and refractory germ cell tumors.
      Responses were observed in approximately 20% of patients, including three of 22
      patients after previous high-dose chemotherapy and one of four patients with
      mediastinal tumors. Gemcitabine may be a reasonable palliative option for
      intensively pretreated patients and should be further investigated to define its
      role in the risk-adapted treatment strategies for germ cell tumors.

PMID- 10080594
TI  - Comparison of the 5-year outcome and morbidity of three-dimensional conformal
      radiotherapy versus transperineal permanent iodine-125 implantation for early
      stage prostatic cancer.
AB  - PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival
      outcome and incidence of late toxicity for patients with early-stage prostate
      cancer treated at a single institution with either three-dimensional conformal
      radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine
      125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer,
      defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score
      of 6 or lower, and stage less than or equal to T2b, were selected for this
      analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and
      145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64
      years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median
      implant dose was 150 Gy. Prostate-specific antigen relapse was defined according
      to the American Society of Therapeutic Radiation Oncology Consensus Statement,
      and toxicity was graded according to the Radiation Therapy Oncology Group
      morbidity scoring scale. The median follow-up times for the 3D-CRT and TPI groups
      were 36 and 24 months, respectively. RESULTS: Eleven patients (8%) in the 3D-CRT
      group and 12 patients (8%) in the TPI group developed a biochemical relapse. The
      5-year PSA relapse-free survival rates for the 3D-CRT and the TPI groups were 88%
      and 82%, respectively (P = .09). Protracted grade 2 urinary symptoms were more
      prevalent among patients treated with TPI compared with 3D-CRT. Grade 2 urinary
      toxicity, which was manifest after the implant and persisted for more than 1 year
      after this procedure, was observed in 45 patients (31%) in the TPI group. In
      these 45 patients, the median duration of grade 2 urinary symptoms was 23 months
      (range, 12 to 70 months). On the other hand, acute grade 2 urinary symptoms
      resolved within 4 to 6 weeks after completion of 3D-CRT, and the 5-year actuarial
      likelihood of late grade 2 urinary toxicity for the 3D-CRT group was only 8%. The
      5-year actuarial likelihood of developing a urethral stricture (grade 3 urinary
      toxicity) for the 3D-CRT and TPI groups was 2% and 12%, respectively (P<.0002).
      Of 45 patients who developed grade 2 or higher urinary toxicity after TPI, the
      likelihood of resolution or significant improvement of these symptoms at 36
      months from onset was 59%. The 5-year likelihood of grade 2 late rectal toxicity
      for the 3D-CRT and TPI patients was similar (6% and 11%, respectively; P = .97).
      No patient in either group developed grade 3 or higher late rectal toxicity. The
      5-year likelihood of posttreatment erectile dysfunction among patients who were
      initially potent before therapy was 43% for the 3D-CRT group and 53% for the TPI
      group (P = .52). CONCLUSION: Both 3D-CRT and TPI are associated with an excellent
      PSA outcome for patients with early-stage prostate cancer. Urinary toxicities are
      more prevalent for the TPI group and subsequently resolve or improve in most
      patients. In addition to evaluating long-term follow-up, future comparisons will
      require detailed quality-of-life assessments to further determine the impact of
      these toxicities on the overall well-being and quality of life of the individual
      patient.

PMID- 10080595
TI  - Sarcomatoid renal cell carcinoma: biologic behavior, prognosis, and response to
      combined surgical resection and immunotherapy.
AB  - PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors
      that respond poorly to immunotherapy. We report the outcomes of 31 patients with
      sarcomatoid RCC treated with a combination of surgical resection and
      immunotherapy. PATIENTS AND METHODS: Patients were identified from the database
      of the University of California Los Angeles Kidney Cancer Program. We
      retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid
      RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis,
      pathologic stage, and type of immunotherapy were abstracted from the medical
      records. The primary end point analyzed was overall survival, and a multivariate
      analysis was performed to distinguish any factors conferring an improved
      survivorship. RESULTS: Twenty-six percent of patients were male and 74% were
      female, and the median age was 59 years (range, 34 to 73 years). Length of follow
      up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%)
      had known metastases at the time of radical nephrectomy (67% had lung metastases
      and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain
      metastases). Twenty-five patients (81%) received immunotherapy, including low
      dose interleukin (IL)-2-based therapy (five patients), tumor-infiltrating
      lymphocyte-based therapy plus IL-2 (nine patients), high-dose IL-2-based therapy
      (nine patients), dendritic cell vaccine-based therapy (one patient), and
      interferon alpha-based therapy alone (one patient). Two patients (6%) achieved
      complete responses (median duration, 46+ months) and five patients (15%) achieved
      partial responses (median duration, 36 months). One- and 2-year overall survival
      rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex,
      and percentage of sarcomatoid tumor (< or >50%) did not significantly correlate
      with survival. Improved survival was found in patients receiving high-dose IL-2
      therapy compared with patients treated with surgery alone or any other form of
      immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid
      tumor, the relative risk of death was 10.4 times higher in patients not receiving
      high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly
      with outcome, but node-positive patients had a higher death rate per year of
      follow-up than did the rest of the population (1.26 v 0.76, Cox regression
      analysis). CONCLUSION: Surgical resection and high-dose IL-2-based immunotherapy
      may play a role in the treatment of sarcomatoid RCCs in select patients.

PMID- 10080596
TI  - Autoimmunity resulting from cytokine treatment predicts long-term survival in
      patients with metastatic renal cell cancer.
AB  - PURPOSE: In patients undergoing cytokine therapy, systemically applied
      interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) have been reported to
      induce thyroid dysfunction as well as thyroid autoantibodies. We analyzed the
      correlation of thyroid autoimmunity with HLA phenotype, various other autoimmune
      parameters, and patient survival. PATIENTS AND METHODS: For this purpose,
      antithyroglobulin autoantibodies, antimicrosomal thyroid autoantibodies,
      thyroglobulin receptor autoantibodies, thyroid dysfunction, and multiple clinical
      parameters were determined in 329 unselected patients with metastatic renal cell
      cancer before and after systemic IL-2 and IFN-alpha2 therapy. For statistical
      analysis, we used both univariate and multivariate Cox proportional hazards
      models and the two-tailed Fisher's exact test. RESULTS: Antithyroglobulin
      autoantibodies and antimicrosomal thyroid autoantibodies were detected in 60
      patients (18%); positive autoantibody titers of various other autoimmune
      parameters were statistically unrelated. The presence of thyroid autoantibodies
      was correlated with prolonged survival (P<.0001). There was a statistically
      significant difference in frequencies of HLA-Cw7 expression between thyroid
      autoantibody-positive and -negative patients (P< or =.05), and the Cw7 expression
      was associated with prolonged overall survival (P = .009). CONCLUSION: The
      evaluation of thyroid autoantibodies during cytokine therapy could be a useful
      prognostic marker for patients with renal cell carcinoma who benefit from
      cytokine treatment. IL-2- and IFN-alpha2-induced tumor control and prolonged
      survival may require breaking of immunologic tolerance against self-antigens.

PMID- 10080597
TI  - Autotransplants for Hodgkin's disease in patients never achieving remission: a
      report from the Autologous Blood and Marrow Transplant Registry.
AB  - PURPOSE: Hodgkin's disease patients who never achieve complete remission with
      conventional chemotherapy (i.e., those with primary induction failure) have a
      poor prognosis. Some subjects who receive high-dose therapy with autologous
      hematopoietic progenitor-cell infusion experience prolonged progression-free
      survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and
      Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed
      to achieve complete remission after one or more conventional therapy regimens and
      subsequently received an autotransplant between 1989 and 1995 were reviewed.
      RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from
      diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients
      received high-dose chemotherapy without radiation for pretransplantation
      conditioning (n = 107). The regimen most frequently used was cyclophosphamide,
      carmustine, and etoposide (n = 47). Fifteen patients received total-body
      irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem
      cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence
      interval, 7% to 19%). Sixty patients (50%) were considered to have achieved
      complete remission after autotransplantation; 37 of these had negative imaging
      studies, whereas scan abnormalities of unknown significance persisted in 23
      patients. Twenty-seven patients (22%) had no response or progressive disease
      after transplantation. Probabilities of progression-free and overall survival at
      3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence
      interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at
      diagnosis and poor performance score at transplantation were adverse prognostic
      factors for outcome. CONCLUSION: Autotransplants should be considered for
      patients with Hodgkin's disease who do not achieve complete remission with
      conventional therapy.

PMID- 10080598
TI  - Multicenter phase II study of fludarabine phosphate for patients with newly
      diagnosed lymphoplasmacytoid lymphoma, Waldenstrom's macroglobulinemia, and
      mantle-cell lymphoma.
AB  - PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular
      lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high
      complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenstrom's
      macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced
      stage disease and are incurable with standard alkylator-based chemotherapy. A
      phase II trial was undertaken to determine the activity of F-AMP in patients
      newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996,
      78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m2/d for 5
      days, every 4 weeks) until maximum response, plus two further cycles as
      consolidation. The primary end point was response rate; secondary end points
      included time to progression (TTP), duration of response, and overall survival
      (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP
      (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow
      up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma;
      the median duration of response was 2.5 years. The median survival has not yet
      been reached. There was no significant difference in the duration of response or
      OS between patients with different histologies; TTP was shorter in patients with
      MCL (P = .015). Myelosuppression was relatively common, and the treatment-related
      mortality (TRM) was 5%, mostly associated with pancytopenia and infection.
      CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated
      LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is
      low, and the TRM is relatively high. Its role in combination chemotherapy remains
      to be demonstrated.

PMID- 10080599
TI  - Value of combined approach with thallium-201 single-photon emission computed
      tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the
      diagnosis of AIDS-related primary CNS lymphoma.
AB  - PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single
      photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA
      (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL).
      PATIENTS AND METHODS: All human immunodeficiency virus (HIV)-infected patients
      with focal brain lesions observed between June 1996 and March 1998 underwent
      lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain
      reaction (PCR) for EBV-DNA. RESULTS: Thirty-one patients were included, 13 with
      PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive.
      Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95%
      confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor
      patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background
      ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16
      nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased
      201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic
      patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94%
      negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity
      and 100% positive predictive value. The presence of increased uptake and/or
      positive EBV-DNA had 100% sensitivity and 100% NPV. CONCLUSION: Combined SPECT
      and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL.
      Because PCNSL likelihood is extremely high in patients with hyperactive lesions
      and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly
      undergo radiotherapy or multimodal therapy. On the contrary, in patients showing
      hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is
      indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to
      be advisable.

PMID- 10080600
TI  - Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone
      marrow transplantation for chronic myelogenous leukemia: impact of donor
      lymphocyte infusion.
AB  - PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in
      patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell
      depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of
      salvage treatment for patients with DLI after TCD allogeneic BMT prompted an
      evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated
      during the time when DLI has been available. PATIENTS AND METHODS: We performed a
      retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic
      BMT for stable-phase CML and compared these outcomes with those of 40 patients
      who underwent non-TCD allogeneic BMT. All subjects were patients at one of two
      neighboring institutions during a period when DLI was available. All patients
      received marrow from HLA-identical sibling donors, underwent similar
      myeloablative regimens, and had similar pretreatment characteristics. RESULTS:
      After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%,
      P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than
      did the non-TCD group. The 1-year treatment-related mortality rates for the TCD
      group and the non-TCD group were 13% and 29%, respectively (P = .07). The
      estimated 3-year probability of relapse (cytogenetic or hematologic) was higher
      for patients in the TCD group than for patients in the non-TCD group (62% v 24%,
      P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD
      group) received and were assessable for response to DLI. After DLI, 17 of 20
      patients in the TCD group and two of three patients in the non-TCD group achieved
      complete remission. Donor lymphocyte infusion induced GVHD in nine of 23
      patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39
      assessable patients in the non-TCD group remained alive without evidence of
      disease. The estimated 3-year overall survival rates were similar for the TCD
      group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow
      up, there was no difference in the overall prevalence of GVHD or the proportion
      of patients requiring immunosuppressive agents between groups. CONCLUSION: These
      results suggest that the combination of T-cell depletion and post-BMT DLI is a
      viable treatment option for patients undergoing allogeneic BMT for CML and should
      be prospectively compared with traditional forms of GVHD prophylaxis.

PMID- 10080601
TI  - Secondary leukemia or myelodysplastic syndrome after treatment with
      epipodophyllotoxins.
AB  - PURPOSE: The incidence of secondary leukemia after epipodophyllotoxin treatment
      and the relationship between epipodophyllotoxin cumulative dose and risk are not
      well characterized. The Cancer Therapy Evaluation Program (CTEP) of the National
      Cancer Institute (NCI) has developed a monitoring plan to obtain reliable
      estimates of the risk of secondary leukemia after epipodophyllotoxin treatment.
      METHODS: Twelve NCI-supported cooperative group clinical trials were identified
      that use epipodophyllotoxins at low (<1.5 g/m2 etoposide), moderate (1.5 to 2.99
      g/m2 etoposide), or higher (> or =3.0 g/m2 etoposide) cumulative doses. Cases of
      secondary leukemia (including treatment-related myelodysplastic syndrome)
      occurring on these trials have been reported to CTEP, as has duration of follow
      up for all patients, thereby allowing calculation of cumulative 6-year incidence
      rates of secondary leukemia for each etoposide dose group. RESULTS: The
      calculated cumulative 6-year risks for development of secondary leukemia for the
      low, moderate, and higher cumulative dose groups were 3.3%, (95% upper confidence
      bound of 5.9%), 0.7% (95% upper confidence bound of 1.6%), and 2.2%, (95% upper
      confidence bound of 4.6%), respectively. CONCLUSION: Within the context of the
      epipodophyllotoxin cumulative dose range and schedules of administration
      encompassed by the monitoring plan regimens, and within the context of multiagent
      chemotherapy regimens that include alkylating agents, doxorubicin, and other
      agents, factors other than epipodophyllotoxin cumulative dose seem to be of
      primary importance in determining the risk of secondary leukemia. Data obtained
      by the CTEP secondary leukemia monitoring plan support the relative safety of
      using epipodophyllotoxins according to the therapeutic plans outlined in the
      monitored protocols.

PMID- 10080602
TI  - K-ras mutations in DNA extracted from the plasma of patients with pancreatic
      carcinoma: diagnostic utility and prognostic significance.
AB  - PURPOSE: Previous studies have demonstrated the presence of K-ras mutations in
      the plasma of patients with pancreatic carcinoma. However, the diagnostic utility
      and the prognostic significance of this finding have never been addressed.
      PATIENTS AND METHODS: Forty-four consecutive patients with histologically
      confirmed primary pancreatic ductal adenocarcinoma were included. A control group
      of 37 patients with chronic pancreatitis, 10 patients with other tumors of the
      pancreatic area, nine patients with acute pancreatitis, and four healthy
      volunteers was also included. Plasma DNA was isolated and K-ras codon-12
      mutations were analyzed by means of restriction fragment length polymorphism
      polymerase chain reaction and single-strand conformation polymorphism techniques.
      Patients were followed up to establish their clinical outcome. RESULTS: The
      mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients
      with pancreatic ductal adenocarcinoma; this finding was related to the tumor
      stage (P = .05), mainly in the presence of distant metastases (P = .02). In
      addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37
      patients with chronic pancreatitis. In the subset of patients with pancreatic
      masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic
      adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma
      patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter
      survival time than patients with the wild-type gene (P<.005), and plasma K-ras
      mutations were identified as the only independent prognostic factor (odds ratio,
      1.51; 95% confidence interval, 1.02 to 2.23). CONCLUSION: Plasma K-ras analysis
      is a highly specific, low-sensitivity approach that has diagnostic and prognostic
      clinical implications in patients with pancreatic carcinoma.

PMID- 10080603
TI  - Phase I-II study of gemcitabine and fluorouracil as a continuous infusion in
      patients with pancreatic cancer.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities,
      and efficacy of gemcitabine combined with fluorouracil (5-FU) in patients with
      pancreatic cancer. PATIENTS AND METHODS: Patients with measurable, locally
      advanced, nonresectable or metastatic pancreatic cancer were candidates for the
      study. 5-FU was given via protracted venous infusion (PVI) at a fixed dosage of
      200 mg/m2/d, and gemcitabine was administered weekly for 3 consecutive weeks
      every 4 weeks. The initial dose of gemcitabine was 700 mg/m2 and was escalated in
      increments of 100 mg/m2/wk until the appearance of severe toxicity. Measurements
      of efficacy included the following: response rate; clinical benefit response,
      which is a composite measurement of pain, performance status, and weight loss;
      time to disease progression; and survival. RESULTS: Twenty-six patients received
      a total of 109 courses. Dose-limiting toxicity, which consisted of grade 4
      neutropenia with fever (one patient) and grade 4 thrombocytopenia (one patient),
      was observed in two of three patients treated with 1,100 mg/m2/wk of gemcitabine.
      On the basis of these results, the MTD of gemcitabine with 5-FU via PVI on this
      schedule was 1,000 mg/m2. Sixteen patients developed grade 3-4 neutropenia, and
      three patients developed grade 3-4 thrombocytopenia. Grade 3-4 nonhematologic
      toxicity consisted of diarrhea (two patients) and cutaneous toxicity, asthenia,
      edema, mucositis, and nausea and vomiting (one patient each). The delivered dose
      intensity of gemcitabine was similar at the 1,000 mg/m2 dose level (599 mg/m2/wk)
      as at the 900 mg/m2 (601 mg/m2/wk) dose level. For this reason, the recommended
      dose of gemcitabine for phase II evaluation on this schedule was 900 mg/m2. Five
      patients had objective responses (one complete response and four partial
      responses; response rate, 19.2%; 95% confidence interval [CI], 6.5 to 39.3), and
      10 patients had improvement of disease-related symptoms (45%; 95% CI, 24 to 67).
      After a median follow-up of 17.7 months (range, 7.8 to 24.8 months), the median
      progression-free survival and overall survival times were 7.4 months (95% CI, 3.3
      to 11.4) and 10.3 months (95% CI, 8.1 to 12.5), respectively. CONCLUSION: The MTD
      of gemcitabine when combined with 5-FU via PVI on this schedule was 1,000 mg/m2/
      wk; however, on the basis of administered dose-intensity, the recommended dose
      for additional investigation is 900 mg/m2. This combination chemotherapy regimen
      was well tolerated and showed promising antitumor activity in the treatment of
      pancreatic cancer.

PMID- 10080604
TI  - Prognostic value of p53 genetic changes in colorectal cancer.
AB  - PURPOSE: To explore whether there is a linkage between different mutations in the
      p53 gene in primary colorectal cancer and the risk of death from colorectal
      cancer in a large group of patients with long follow-up. We also compared a
      complementary DNA-based sequencing method and an immunohistochemical (IHC) method
      for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND
      METHODS: The entire coding region of the p53 gene was sequenced in 191 frozen
      tumor samples collected from January 1988 to November 1992. RNA was extracted and
      synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the
      DO-7 monoclonal antibody was used in the IHC assessments. RESULTS: Mutations were
      detected in 99 samples (52%) from 189 patients. There was a significant
      relationship between the p53 mutational status and the cancer-specific survival
      time, with shorter survival time for patients who had p53 mutations than for
      those who did not (P = .01, log-rank test). Mutations outside the evolutionarily
      conserved regions were associated with the worst prognosis. Multivariate analysis
      showed that the presence of p53 mutations was an independent prognostic factor
      (relative hazard, 1.7, P = .03). There was no significant relationship between
      overexpression of p53 protein, as determined by IHC analysis, and cancer-specific
      survival. CONCLUSION: Mutational analyses of the p53 gene, using cDNA sequencing
      in colorectal cancer, provide useful prognostic information. In addition, cDNA
      sequencing gives better prognostic information than IHC assessment of p53 protein
      overexpression.

PMID- 10080605
TI  - Octreotide acetate long-acting formulation versus open-label subcutaneous
      octreotide acetate in malignant carcinoid syndrome.
AB  - PURPOSE: Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea
      and flushing associated with carcinoid syndrome but requires long-term multiple
      injections daily. A microencapsulated long-acting formulation (LAR) of octreotide
      acetate has been developed for once-monthly intramuscular dosing. PATIENTS AND
      METHODS: A randomized trial compared double-blinded octreotide LAR at 10, 20, and
      30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment
      of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC
      octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and
      who returned for at least the week 20 evaluation constituted the efficacy
      assessable population. RESULTS: Complete or partial treatment success was
      comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg,
      71.4%; 30 mg, 61.9%; P> or =.72 for all pairwise comparisons). Control of stool
      frequency was similar in all treatment groups. Flushing episodes were best
      controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least
      effective in the control of flushing. Treatment was well tolerated by patients in
      all four groups. CONCLUSION: Once octreotide steady-state concentrations are
      achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as
      well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended.
      Supplemental SC octreotide is needed for approximately 2 weeks after initiation
      of octreotide LAR treatment. Occasional rescue SC injections may be required for
      possibly 2 to 3 months until steady-state octreotide levels from the LAR
      formulation are achieved.

PMID- 10080606
TI  - Role of transforming growth factor-beta 1 in invasion and metastasis in gastric
      carcinoma.
AB  - PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is a major modulator of
      cellular proliferation and extracellular matrix formation. We determined the role
      of TGF-beta1 in invasion and metastasis in gastric cancer. MATERIALS AND METHODS:
      We detected TGF-beta1 expression in primary and lymph node metastatic lesions of
      gastric cancer, using an antibody and in situ hybridization. The plasma TGF-beta1
      levels in the peripheral vein and in the tumor drainage vein were assayed.
      RESULTS: In the cytoplasm of cancer cells, TGF- beta1 was immunostained in 35.9%
      (78 of 217) of primary gastric carcinomas, and this expression was confirmed by
      in situ hybridization. Of 59 gastric carcinomas with a TGF-beta1-negative primary
      tumor, metastatic lymph nodes were positive for TGF-beta1 staining in 32 cases
      (54.2%). Positive staining of TGF-beta1 in gastric cancer tissues was closely
      related to serosal invasion, infiltrative growth, and lymph node metastasis.
      Multivariate analysis showed that the expression of TGF-beta1 was an independent
      risk factor for serosal invasion and infiltrative growth of the tumor. The plasma
      level of TGF-beta1 did not differ between TGF-beta1-negative and -positive
      groups. There were also no differences in plasma TGF-beta1 levels among each
      tumor stage, between the peripheral and the tumor drainage veins, and between
      preoperative and postoperative testings. CONCLUSION: Transforming growth factor
      beta1 is closely related to the invasion and metastasis of gastric cancer, and
      production of TGF-beta1 in the tumor does not contribute to the total amount of
      TGF-beta1 in the blood circulation. We interpret our observations to mean that in
      a tumor microenvironment, TGF-beta1 alters the biologic behavior of the tumor.

PMID- 10080607
TI  - Prospective study of the clinical course, prognostic factors, causes of death,
      and survival in patients with long-standing Zollinger-Ellison syndrome.
AB  - PURPOSE: The long-term clinical course of unselected patients with gastrinomas as
      well as other functional pancreatic endocrine tumors (PETs) in whom the excess
      hormone state is controlled is largely unknown. To address this issue, patients
      with gastrinomas were assessed. PATIENTS AND METHODS: Two hundred twelve patients
      with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had
      controlled acid hypersecretion and were assessed yearly, with a mean follow-up
      period of 13.8+/-0.6 years (range, 0.1 to 31 years). Annual assessments of
      possible factors that might affect prognosis or treatment approaches were
      performed, such as those for tumor size and location; the presence, location, and
      extent of metastases; and the occurrence of ectopic Cushing's syndrome or another
      PET syndrome. Deaths were categorized as ZES-related or non-ZES-related and
      classified into different causes. RESULTS: Thirty-one percent of patients died,
      all of non-acid-related causes. One half died of a ZES-related cause; they
      differed from those who died of non-ZES deaths by having a large primary tumor,
      more frequently a pancreatic tumor; lymph node, liver, or bone metastases;
      ectopic Cushing's syndrome; or higher gastrin levels. The extent of liver
      metastases correlated with survival rate. The presence of liver metastases alone
      only moderately decreased survival time; however, the additional development of
      bone metastases or ectopic Cushing's syndrome markedly decreased survival rate.
      CONCLUSIONS: In ZES, gastrinoma growth is now the main single determinant of long
      term survival, with one half of patients dying a gastrinoma-related death and
      none an acid-related death. Large primary tumors that are pancreatic in location,
      the development of liver metastases, (especially if associated with bone
      metastases or Cushing's syndrome), and the extent of liver metastases are all
      important prognostic factors. The identification of these factors allows the
      recognition of subgroups that can be used to tailor antitumor treatment
      approaches.

PMID- 10080608
TI  - Preradiotherapy computed tomography as a predictor of local control in
      supraglottic carcinoma.
AB  - PURPOSE: To determine the utility of pretreatment computed tomography (CT) for
      predicting primary site control in patients with supraglottic squamous cell
      carcinoma (SCC) treated with definitive radiotherapy (RT). MATERIALS AND METHODS:
      Pretreatment CT studies in 63 patients were reviewed. Minimum length of follow-up
      was 2 years. Local recurrence and treatment complications resulting in permanent
      loss of laryngeal function were documented. Tumor volume was calculated using a
      computer digitizer, and pre-epiglottic space (PES) spread was estimated. The data
      were analyzed using a combination of Fisher's exact test, logistic regression
      modeling, and multivariate analyses. Five-year local control rates were
      calculated using the product-limit method. RESULTS: Local control rates were
      inversely and roughly linearly related to tumor volume, although there seemed to
      be a threshold volume at which primary site prognosis diminished. Local control
      was 89% in tumors less than 6 cm3 and 52% when volumes were > or =6 cm3 (P =
      .0012). The likelihood of maintaining laryngeal function also varied with tumor
      volume: 89% for tumors less than 6 cm3 and 40% for tumors > or =6 cm3 (P =
      .00004). Pre-epiglottic space involvement by tumor of > or =25% was associated
      with a reduced chance of saving the larynx (P = .0076). Multivariate analyses
      revealed that only tumor volume independently altered these end points.
      CONCLUSION: Pretreatment CT measurements of tumor volume permits stratification
      of patients with supraglottic SCC treated with RT alone (which allows
      preservation of laryngeal function) into groups in which local control is more
      likely and less likely. Pre-epiglottic space spread is not a contraindication to
      using RT as the primary treatment for supraglottic SCC.

PMID- 10080609
TI  - Radiation therapy with concomitant hydroxyurea and fluorouracil in stage II and
      III head and neck cancer.
AB  - PURPOSE: In 1986, a multi-institutional phase II trial was begun to study the use
      of chemotherapy with concomitant radiation in patients with stage II and III head
      and neck cancer. End points were overall survival, progression-free survival,
      local/regional control, and toxicity in the setting of organ preservation with
      concomitant treatment. METHODS: Eligible patients with stage II or III disease
      received chemotherapy and radiation on a 2-week cycle. Chemotherapy consisted of
      continuous infusion fluorouracil (5-FU) at 800 mg/m2/d for 5 consecutive days
      (days 1 to 5) and hydroxyurea (HU) at 1 g orally every 12 hours for 13 doses
      starting the evening before the start of irradiation. Radiation therapy was given
      as single 1.8- to 2.0-Gy fractions for 5 consecutive days (days 1 to 5) with
      chemotherapy. Each 5 days of treatment was followed by a 9-day break (days 6 to
      14), during which no additional treatment was given. Treatment cycles were
      repeated until the completion of the planned radiation dose (six to eight
      cycles). RESULTS: Between 1989 and 1996, 60 patients were enrolled. All patients
      were eligible for analysis, with a median follow-up of 52 months for surviving
      patients and 42 months for all patients. Grade 3 to 4 mucositis occurred in 57%
      of patients. The 5 year-actuarial overall survival, progression-free survival,
      and local/regional control were 65%, 82%, and 86%, respectively. Eight patients
      developed local and/or regional recurrence after treatment. Surgical salvage was
      possible in three of these patients. Thus, the ultimate 5-year local/ regional
      control was 91%. CONCLUSION: Concomitant radiation and chemotherapy with 5-FU and
      HU is an effective regimen in patients with stage II and III head and neck
      cancer. Progression-free survival and local/regional control appear to be
      superior to expected rates in patients treated with surgery and radiation.
      Further testing of this regimen in a phase III setting is indicated.

PMID- 10080610
TI  - Procarbazine and high-dose tamoxifen as a second-line regimen in recurrent high
      grade gliomas: a phase II study.
AB  - PURPOSE: A phase II study was conducted in patients with high-grade gliomas that
      recurred after surgery plus radiotherapy and a first-line nitrosourea-based
      regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined
      with high-dose tamoxifen in relation to tumor control, toxicity, and time to
      progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with
      procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d,
      with a 30-day interval between courses. Thirty-four patients had been pretreated
      with a first-line nitrosourea-based chemotherapy regimen (group A), and 19
      patients had also been pretreated with a second-line chemotherapy regimen
      consisting of carboplatin and teniposide (group B). Twenty-one of the patients
      had also been procarbazine pretreated, whereas the remaining 32 patients were not
      procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of
      whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma
      (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR)
      (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence
      interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2;
      95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33
      weeks for patients with AA (P = .006). The median survival time (MST) was 27
      weeks for patients with GBM and 57 weeks for those with AA (P = .006).
      CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably
      high response rate in patients with heavily pretreated high-grade gliomas.
      However, although it resulted in an improvement in the patients' quality of life
      and/or performance status, it was not followed by an increased TTP or MST.

PMID- 10080611
TI  - Combination of chemotherapy with interleukin-2 and interferon alfa for the
      treatment of metastatic melanoma.
AB  - PURPOSE: The primary objective of this clinical study was to assess the
      feasibility of administering recombinant interleukin-2 and recombinant interferon
      alfa-2a before and after combination cytotoxic chemotherapy. After encouraging
      initial responses, the study was expanded to further evaluate the therapeutic
      potential, clarify the toxicities of this regimen, and explore any associated
      immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic
      melanoma, including patients with brain metastases, were treated on this 6-week
      protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine
      (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2)
      on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d)
      were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83
      patients assessable for response, 12 complete and 34 partial responses were
      documented (55% response rate). The median time to disease progression was 7
      months, the median survival from study entry was 12.2 months, and the median
      survival from diagnosis of metastatic disease was 15.5 months. Although patients
      were hospitalized to receive treatment, intensive care unit support generally was
      not needed. Dose-limiting toxicities were related to elevations in serum
      bilirubin and serum creatinine levels. No patient developed a grade 4 clinical
      toxicity. Treatment produced a skin depigmentation, which was associated with
      prolonged survival. CONCLUSION: A plateau in both the survival and time to
      progression curves beyond 2 years (15% of the patients) and a greater than 10%
      disease-free survival beyond 4 years indicate that there may be a long-term
      benefit for some patients. The limited toxicity of this regimen should permit its
      use in most oncology settings. A randomized trial of chemoimmunotherapy versus
      chemotherapy should be performed to establish the value of chemoimmunotherapy for
      melanoma.

PMID- 10080612
TI  - Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment
      of recurrent small-cell lung cancer.
AB  - PURPOSE: Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were
      evaluated in a randomized, multicenter study of patients with small-cell lung
      cancer (SCLC) who had relapsed at least 60 days after completion of first-line
      therapy. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as
      a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV
      (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg)
      infused on day 1 every 21 days (n = 104). Eligibility included the following:
      bidimensionally measurable disease, Eastern Cooperative Oncology Group
      performance status of less than or equal to 2, and adequate marrow, liver, and
      renal function. Response was confirmed by blinded independent radiologic review.
      RESULTS: Response rate was 26 of 107 patients (24.3%) treated with topotecan and
      19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to
      progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median
      survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The
      proportion of patients who experienced symptom improvement was greater in the
      topotecan group than in the CAV group for four of eight symptoms evaluated,
      including dyspnea, anorexia, hoarseness, and fatigue, as well as interference
      with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of
      topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia
      and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8%
      and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively
      (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both
      regimens. CONCLUSION: Topotecan was at least as effective as CAV in the treatment
      of patients with recurrent SCLC and resulted in improved control of several
      symptoms.

PMID- 10080613
TI  - Prognostic significance of K-ras codon 12 mutations in patients with resected
      stage I and II non-small-cell lung cancer.
AB  - PURPOSE: The aim of this study was to investigate the prognostic importance of
      codon 12 K-ras mutations in patients with early-stage non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically
      resected stage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year
      follow-up. We performed polymerase chain reaction analysis of DNA obtained from
      paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K
      ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens
      (16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one
      of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%),
      and two of 20 adenosquamous carcinomas (10%) (P = .001). G to T transversions
      accounted for 71% of the mutations. There was no statistically significant
      difference in overall survival for all patients with K-ras mutations (median
      survival, 39 months) compared with patients without K-ras mutations (median
      survival, 53 months; P = .33). There was no statistically significant difference
      in overall or disease-free survival for subgroups with stage I disease,
      adenocarcinoma, or non-squamous cell carcinoma or for specific amino acid
      substitutions. The median survival time for stage II patients with K-ras
      mutations was 13 months, compared with 38 months for patients without K-ras
      mutations (P = .03). CONCLUSION: Codon 12 K-ras mutations were more common in
      adenocarcinomas than in squamous cell carcinomas. For the subgroup with stage II
      NSCLC, there was a statistically significant adverse effect on survival for the
      presence of K-ras mutations. However, when the entire group was considered, the
      presence of K-ras mutations was not of prognostic significance in this cohort of
      patients with resected early-stage NSCLC.

PMID- 10080614
TI  - Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of
      combination paclitaxel and carboplatin in patients with metastatic non-small-cell
      lung cancer.
AB  - PURPOSE: To determine the maximum-tolerated dose of paclitaxel with carboplatin
      with and without filgrastim support in patients with metastatic non-small-cell
      lung cancer (NSCLC) and to investigate the pharmacokinetics of paclitaxel and
      carboplatin and correlate these with the pharmacodynamic effects. PATIENTS AND
      METHODS: Thirty-six chemotherapy-naive patients with metastatic NSCLC were
      entered into this phase I dose-escalation and pharmacokinetic study. Paclitaxel
      was initially administered as a 24-hour infusion at a fixed dose of 135 mg/m2,
      and the carboplatin dose was escalated in cohorts of three patients, using
      Calvert's formula [dose(mg) = area under the concentration time curve (glomerular
      filtration rate + 25)], to target areas under the concentration time curve (AUCs)
      of 5, 7, 9, and 11 mg/mL x minute. A measured 24-hour urinary creatinine
      clearance was substituted for the glomerular filtration rate. Once the maximum
      tolerated AUC (MTAUC) of carboplatin was reached, the paclitaxel dose was
      escalated to 175, 200, and 225 mg/m2. When the paclitaxel dose escalation began,
      the AUC of carboplatin was reduced to one level below the MTAUC. RESULTS:
      Myelosuppression was the major dose-limiting toxicity. Thrombocytopenia was
      observed at a carboplatin AUC of 11 mg/mL x minute after course 2 and thereafter.
      End-of-infusion plasma paclitaxel concentrations and median duration of time
      above 0.05 microM were similar in course 1 versus course 2 at the 135 and 175
      mg/m2 dose levels. The neutropenia experienced by patients was consistent with
      that observed in patients who had received paclitaxel alone. Measured carboplatin
      AUCs were approximately 12% (20% v 3% with course 1 v course 2, respectively)
      below the desired target, with a standard deviation of 34% at all dose levels. A
      sigmoid-maximum effect model describing the relationship between relative
      thrombocytopenia and measured free platinum exposure indicated that patients who
      received the combination of carboplatin with paclitaxel experienced less severe
      thrombocytopenia than would be expected from carboplatin alone. Of the 36
      patients entered onto the study, one experienced a complete response and 17 had
      partial responses, for an overall response rate of 50%. The recommended doses of
      paclitaxel (24-hour infusion) and carboplatin for future phase II studies of this
      combination are (1) paclitaxel 135 mg/m2 with a carboplatin dose targeted to
      achieve an AUC of 7 mg/mL x minute without filgrastim support; (2) paclitaxel 135
      mg/m2 with a carboplatin dose targeted to achieve an AUC of 9 mg/mL x minute with
      filgrastim support; and (3) paclitaxel 225 mg/m2 with a carboplatin dose targeted
      to achieve an AUC of 7 mg/mL x minute with filgrastim support. CONCLUSION: The
      regimen of paclitaxel and carboplatin is well-tolerated and has promising
      activity in the treatment of NSCLC. There is no pharmacokinetic interaction
      between paclitaxel and carboplatin, but there is a pharmacodynamic, platelet
      sparing effect on this dose-limiting toxicity of carboplatin.

PMID- 10080615
TI  - Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5
      days every 3 weeks in patients with solid tumors.
AB  - PURPOSE: We conducted a phase I dose-escalation trial of orally administered
      irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD), dose
      limiting toxicities (DLTs), pharmacokinetic profile, and antitumor effects in
      patients with refractory malignancies. PATIENTS AND METHODS: CPT-11 solution for
      intravenous (IV) use was mixed with CranGrape juice (Ocean Spray, Lakeville
      Middleboro, MA) and administered orally once per day for 5 days every 3 weeks to
      28 patients. Starting dosages ranged from 20 to 100 mg/m2/d. RESULTS: Grade 4
      delayed diarrhea was the DLT at the 80 mg/m2/d dosage in patients younger than 65
      years of age and at the 66 mg/m2/d dosage in patients 65 or older. The other most
      clinically significant toxicity of oral CPT-11 was neutropenia. A linear
      relationship was found between dose, peak plasma concentration, and area under
      the concentration-time curve (AUC) for both CPT-11 and SN-38 lactone, implying no
      saturation in the conversion of irinotecan to SN-38. The mean metabolic ratio
      ([AUC(SN-38 total) + AUC(SN-38G total)]/AUC(CPT-11 total)) was 0.7 to 0.8, which
      suggests that oral dosing results in presystemic conversion of CPT-11 to SN-38.
      An average of 72% of SN-38 was maintained in the lactone form during the first 24
      hours after drug administration. One patient with previously treated colorectal
      cancer and liver metastases who received oral CPT-11 at the 80 mg/m2/d dosage
      achieved a confirmed partial response. CONCLUSION: The MTD and recommended phase
      II dosage for oral CPT-11 is 66 mg/m2/d in patients younger than 65 years of age
      and 50 mg/m2/d in patients 65 or older, administered daily for 5 days every 3
      weeks. The DLT of diarrhea is similar to that observed with IV administration of
      CPT-11. The biologic activity and favorable pharmacokinetic characteristics make
      oral administration of CPT-11 an attractive option for further clinical
      development.

PMID- 10080616
TI  - Phase I study of liposomal vincristine.
AB  - PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter
      distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary
      objectives were to determine the maximum-tolerated dose (MTD), recommended phase
      II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS).
      PATIENTS AND METHODS: Twenty-five patients with histologically confirmed
      malignancies were enrolled and assessable. Vincristine doses were increased from
      0.5 mg/m2 to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m2 with cohorts of three or more
      patients per dose level. A total of 64 courses of ONCO-TCS were administered
      intravenously once every 3 weeks. The pharmacokinetics of total vincristine
      content in plasma were determined using a high-performance liquid chromatography
      method. RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m2;
      however, 2.4 mg/m2 was defined as the MTD and 2.0 mg/m2 as the phase II
      recommended dose. Pain and obstipation were the dose-limiting toxicites. Other
      toxicities were fever, rigors, fatigue, myalgias, and peripheral neuropathy.
      Hematologic toxicity was mild. All patients who were treated with doses above 1.5
      mg/m2 received in excess of 2.0 mg of vincristine, with doses as high as 6.2 mg.
      One partial response was seen in a patient with pancreatic cancer. Tumor response
      not meeting partial response criteria was seen in two other patients.
      Pharmacokinetic studies revealed significantly elevated concentrations of total
      vincristine, but parameters varied and were not directly correlated with toxicity
      or response. CONCLUSION: The ability to administer elevated doses of vincristine,
      as well as indications of efficacy, suggests that ONCO-TCS warrants further
      clinical investigation in a phase II setting.

PMID- 10080617
TI  - Health-related quality of life 1 year after allogeneic or autologous stem-cell
      transplantation: a prospective study.
AB  - PURPOSE: To evaluate health-related quality of life (HRQOL) in adults treated
      with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT)
      stem-cell transplantation 1 year after transplantation, using data from
      concurrent lymphoma patients receiving combination chemotherapy (CT) as a
      reference. MATERIALS AND METHODS: Forty-one leukemia patients (SCT group), 51
      lymphoma patients (ASCT group), and 85 CT patients completed the European
      Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at
      baseline and after 1 year. RESULTS: The SCT group (median age, 36 years) had
      better functioning scores and less symptomatology at baseline compared with the
      ASCT (median age, 41 years) and CT (median age, 37 years) groups. Statistically
      significant differences of 10 or more points on the 0 to 100 scales were found
      for 10 of 15 scales and items (P< or =.01) between the SCT and ASCT groups.
      Global quality of life (79 v 58, P<.0001), role function (83 v 65, P = .001),
      sleep disturbances (6 v 28, P<.0001), and fatigue (25 v 44, P = .0001) deviated
      most. The differences were 10 or more points for seven of 15 scales and items
      comparing the SCT and CT groups, with sleep disturbances (6 v 35, P<.0001) and
      pain (11 v 29, P<.01) deviating most. Differences across groups were smaller
      after 1 year; cognitive function was the only scale with a statistically
      significant difference (ASCT 80 v CT 89; P = .002). Patterns of change in HRQOL
      scores were different between groups during follow-up. A great improvement was
      found in the ASCT group (P<.01 for emotional and role function, fatigue,
      appetite, and constipation), whereas no significant changes were observed for the
      SCT group. CONCLUSION: Prospective studies with extended follow-up periods are
      necessary to separate a slow recovery process from more permanently reduced HRQOL
      after transplantation and to examine the late side effects from previous
      treatment.

PMID- 10080618
TI  - Cancer control in susceptible groups: opportunities and challenges.
AB  - Cancer mortality rates in the United States have risen throughout most of this
      century, and a downward trend has just emerged in recent years. Nevertheless, it
      is predicted that cancer will soon be the leading cause of death among Americans.
      To gain new knowledge of etiology, we have studied persons at highest risk as
      human models of cancer susceptibility. Clinical observations at the bedside are
      used to generate etiologic hypotheses that are tested in epidemiologic studies.
      Companion laboratory studies can identify biologic mechanisms of predisposition.
      Data show that inborn mutations in cancer-predisposing genes, such as BRCA1 and
      BRCA2, markedly increase the risk of cancers at unusually early ages. Increasing
      numbers of these highly penetrant genes are being identified. These discoveries
      have created new opportunities for genetic testing to identify cancer-prone
      individuals. Individuals found to be carriers can be offered counseling to avoid
      environmental exposures that further elevate risk, intensive medical surveillance
      for early detection, participation in chemoprevention trials, and prophylactic
      surgery to remove at-risk tissues. However, genetic knowledge can have adverse
      effects, including psychologic distress, social stigmatization, and loss of
      health insurance. Research is needed to maximize benefits and minimize risks to
      the susceptible populations. Professional and public education can promote
      appropriate use of genetic data, and legislation may be required to prevent
      discrimination. Knowledge of these highly penetrant genes can be extended to
      common polymorphisms that modify cancer risk associated with exposures to
      environmental carcinogens.

PMID- 10080619
TI  - Two uncommon lymphomas. Case 1: abdominal Burkitt's lymphoma.

PMID- 10080620
TI  - Two uncommon lymphomas. Case 2: signet ring lymphoma of the bone marrow.

PMID- 10080621
TI  - Coming together to conquer cancer.

PMID- 10080622
TI  - MOPP versus ABVD and low-dose versus high-dose irradiation in Hodgkin's disease
      at intermediate and advanced stages: analysis of a meta-analysis by clinicians.

PMID- 10080623
TI  - Chemotherapy of advanced non-small-cell lung cancer: "Those who cannot remember
      the past are condemned to repeat it".

PMID- 10080624
TI  - Risk of risk-based mammography screening, ages 40 to 49. American College of
      Radiology Task Force on Breast Cancer.

PMID- 10080625
TI  - Efficacy of controlled-release oxycodone.

PMID- 10080626
TI  - Wherefore global quality-of-life assessment?

PMID- 10080627
TI  - Gas chromatography of bile acids.
AB  - Bile acids, the end products of cholesterol metabolism in the liver, are of vital
      importance in the tissue distribution of cholesterol. Abnormalities in
      cholesterol biosynthesis or metabolism are often reflected in the proportions,
      concentrations and conjugation of bile acids in various tissues and determination
      of bile acids in these tissues is important in the diagnosis of hepatobiliary
      diseases. Several methods for quantitative determination of bile acids in
      biological fluids are known and have been reviewed. In this review, we have
      discussed the gas-chromatographic method for determination of bile acids with
      special reference to bile acid quantitation in plasma, bile, urine and stool.

PMID- 10080628
TI  - Capillary gas chromatographic determination of putrescine and cadaverine in serum
      of cancer patients using trifluoroacetylacetone as derivatizing reagent.
AB  - Trifluoroacetylacetone (FAA) derivatives of 1,4-diaminobutane (putrescine) (Pu)
      and 1,5-diaminopentane (cadaverine) (CA) were prepared and characterized by
      elemental microanalysis, IR, and mass spectrometry. Diamine derivatives were
      eluted from capillary gas chromatographic (CGC) column BP1 (12 m x 0.22 mm I.D.)
      or BP5 (50 m x 0.22 mm) with layer thickness 0.25 microm, using nitrogen as a
      carrier gas and flame ionization detection (FID). A solvent extraction procedure
      was developed for the extraction of Pu and CA from aqueous solution with a linear
      calibration range 0-20 microg/0.2 ml of extract with a detection limit of 0.5-0.6
      ng/injection. The method was applied for the determination of Pu and CA in the
      serum of five cancer patients before and after radiotherapy. The serum of two
      healthy persons was also analyzed for Pu and CA contents. Pu and CA
      concentrations were found within the range 1.16-3.96 microg/ml and 0.88-1.46
      microg/ml in cancer patients as compared to 0.11-0.16 microg/ml and 0.06-0.075
      microg/ml respectively in healthy persons with a coefficient of variation (CV)
      within 0.62-5.47%. Pu and CA concentrations decreased on radiotherapy in cancer
      patients, but were much higher than in healthy persons.

PMID- 10080629
TI  - Association and dissociation properties of natural human interferon gamma.
AB  - The properties of natural human interferon gamma (IFN-gamma) molecules dissolved
      in protein-denaturing and non-denaturing solvents were examined by high
      performance size-exclusion chromatography on a gel permeation column. IFN-gamma
      and tritium-labeled IFN-gamma molecules formed either dimers (>90.5%) with the
      molecular mass of 60 kDa or probably tetramers (<9.5%) with the molecular mass of
      approximately 100 kDa in non-denaturing solvents, and no monomer was detected.
      These oligomers were dissociated in protein-denaturing solvents such as 6 M
      guanidine hydrochloride, and IFN-gamma existed as monomers. There is no effect on
      formation of the monomer based on the dissociation of oligomers by acid treatment
      at pH 4.0. The monomers in protein-denaturing solvents formed dimers by
      association when applied to a column equilibrated with a non-denaturing solvent
      of phosphate buffer, pH 7.0. In conclusion, natural human IFN-gamma forms
      oligomers, particularly dimers, in non-denaturing solution, and this oligomer
      formation is a reversible reaction.

PMID- 10080630
TI  - Rapid on-line microdialysis hyphenated technique for the dynamic monitoring of
      extracellular pyruvate, lactic acid and ascorbic acid during cerebral ischemia.
AB  - Rapid on-line microdialysis coupled with liquid chromatography was developed for
      the continuous monitoring of brain neurochemicals during cerebral ischemia.
      Isocratic separation of these analytes was achieved within 3 min, hence, over 80
      analyses could be performed in a 4-h experiment. The dead volume of the
      microdialysis system was estimated to be less than 10 microl. The detection
      limits of the present assay, at a signal-to-noise ratio of five, were 2.0, 0.2
      and 0.5 microM, for lactic acid, pyruvate and ascorbic acid, respectively. To
      validate this assay, a transient ischemia was produced by occlusion of two common
      carotid arteries for 10 min in an anesthetized gerbil. A microdialysis probe was
      inserted into the striatum of the gerbil to simultaneously monitor pyruvate,
      lactic acid and ascorbic acid during cerebral ischemia. Significant and dynamic
      changes in these analytes could be resolved in 3-min intervals. This rapid assay
      can be used as a tool to study dynamic changes in neurochemicals of the brain,
      such as during cerebral ischemia.

PMID- 10080631
TI  - Simultaneous determination of estriol and estriol 3-sulfate in serum by column
      switching semi-micro high-performance liquid chromatography with ultraviolet and
      electrochemical detection.
AB  - A column-switching HPLC with semi-microcolumn enabled us a direct and
      simultaneous analysis of estriol (E3) and estriol 3-sulfate (E3 S) in human serum
      in combination with ultraviolet (for E3 S) and electrochemical (for E3)
      detectors. The mobile phases (phosphate buffer pH 7.0) contained 5 mM tetra-n
      butylammonium ion (TBA) as a counter ion for E3 S. Serum samples were diluted
      with 200 mM phosphate buffer (pH 7.0) containing 100 mM TBA, then injected to the
      pre-column. After serum proteins had flowed out from the pre-column, E3 and E3 S
      were transferred to the enrichment column. Subsequently the analytes were eluted
      to the analytical column. Detection limits of E3 and E3 S in human serum were 2.5
      ng/ml and 295 ng/ml. Serum E3 and E3 S levels (mean +/- SD) of umbilical artery
      from 18 full-term healthy neonates were 33+/-23 ng/ml and 1.26+/-0.69 microg/ml,
      respectively.

PMID- 10080632
TI  - Simultaneous determination of basal and evoked output levels of aspartate,
      glutamate, taurine and 4-aminobutyric acid during microdialysis and from
      superfused brain slices.
AB  - A HPLC method, involving pre-column derivatisation with o-phthalaldehyde and
      fluorescence detection, is described. It allows the resolution of aspartate,
      glutamate, taurine and GABA, in a single run with detection limits of 3.2, 1.7,
      1.4 and 2 fmol/microl of perfusate, respectively. It is sufficiently sensitive
      and rapid (15 min) for the determination "on line" of the four amino acids in
      perfusates obtained during in vivo microdialysis experiments. The procedure has
      been used to determine basal, K+ - or veratridine-stimulated release of these
      amino acids in different brain areas during microdialysis and from perfused
      tissue slices.

PMID- 10080633
TI  - Purification of immunoglobulins G by protein A/G affinity membrane
      chromatography.
AB  - An affinity membrane grafted with protein A/G or protein A was characterized for
      human and mouse immunoglobulins G purification. Breakthrough curves up to ligand
      saturation were measured and used to study the effects of flow velocities, feed
      solution concentrations and protein A/G versus protein A membranes. Increased
      flow-rate did not decrease the amount of IgG bound to the membranes. Increased
      feed solution concentration allowed more IgG to bind prior to breakthrough.
      Kinetic parameters for immunoglobulins G sorption to immobilized protein A were
      measured in batch experiments. The static binding capacity was determined to be
      6.6 mg ml(-1) membrane volume. Finally, this affinity membrane was used to purify
      IgG from cell culture supernatant. The electrophoresis of the purified IgG
      fractions did not show any contaminant.

PMID- 10080634
TI  - Comparison of three liquid chromatographic methods for egg-white protein
      analysis.
AB  - This paper describes and compares three chromatographic methods for the analysis
      of egg-white proteins. Gel-permeation chromatography allowed the separation of
      seven peaks from egg white, with an almost total protein recovery. A clean
      separation of ovomucin and lysozyme from the bulk of the proteins was obtained
      with this method. Reversed-phase high-performance liquid chromatography led to
      the fractionation of at least eight peaks. With this chromatographic method, the
      recovery was relatively poor. Approximately 30% of the ovalbumin was retained in
      the column after the elution. Finally, eleven chromatographic peaks were
      separated from egg white by high-performance liquid chromatography on an anion
      exchange column. The recovery of proteins was almost total. The latter method
      afforded higher resolution.

PMID- 10080635
TI  - Alterations of asparagine-linked sugar chains of N-acetyl beta-D-hexosaminidase
      during human renal oncogenesis: a preliminary study using serial lectin affinity
      chromatography.
AB  - Enzymatic properties and asparagine (Asn)-linked sugar-chain structures of N
      acetyl beta-D-hexosaminidase A (Hex A) were compared in human tissues between
      normal renal cortex and renal cell carcinoma (RCC). No significant differences
      between the two Hex A preparations were observed with respect to enzymatic
      properties such as molecular mass, Michaelis-Menten value or optimal pH. With RCC
      preparations, relatively more Hex A passed through the concanavalin A (Con A)
      column, bound weakly to Con A, or bound strongly to Con A and also to the wheat
      germ agglutinin (WGA) column, than with preparations from normal renal cortex. In
      contrast, relatively less Hex A bound strongly to the Con A column, but passed
      through the WGA column with RCC preparations than with those from normal renal
      cortex. Asn-linked sugar-chain structures might apparently be altered during
      human renal oncogenesis.

PMID- 10080636
TI  - Simultaneous determination of purine metabolites, creatinine and pseudouridine in
      ruminant urine by reversed-phase high-performance liquid chromatography.
AB  - Determination of purine metabolites, pseudouridine and creatinine in both bovine
      and ovine urine using high-performance liquid chromatography (HPLC) is described.
      Following dilution and filtration, urine samples were analysed directly.
      Separation and quantification was achieved using a Spherisorb ODS II C18 column
      (250x4.6 mm I.D.) under isocratic conditions. The mobile phase contained 7.5 mM
      ammonium dihydrogen phosphate, 10 mM sodium 1-heptane sulphonic acid and 1.0 mM
      triethylamine at pH 3.0. Chromatography was achieved at a flow-rate of 1.0 ml/min
      and monitoring column effluent at 218 nm. Total analysis time was 60 min.
      Recovery of all compound standards added to urine was above 96%. In all cases,
      close spectral matches of compound standards and corresponding identified peaks
      in ovine and bovine urine were obtained. Lowest detectable concentrations of
      allantoin, uric acid, xanthine, hypoxanthine, creatinine and pseudouridine were
      1.1, 1.0, 1.0, 3.0 and 0.4 micromol/l, respectively. Advantages of simultaneous
      determination of purine metabolites, creatinine and pseudouridine in ruminant
      urine collected from both sheep and cattle exist over current methods.

PMID- 10080637
TI  - Gas chromatography-electron-capture detection of urinary methylhippuric acid
      isomers as biomarkers of environmental exposure to xylene.
AB  - Methylhippuric acid isomers (MHAs), urinary metabolites of xylenes, were
      determined, after clean-up by C18-SPE and esterification with
      hexafluoroisopropanol and diisopropylcarbodiimide, by GC with ECD detection, on
      an SPB-35 capillary column (30 m, 0.32 mm I.D., 0.25 microm film thickness, beta
      = 320). S-benzyl-mercapturic acid was used for internal standardization.
      Chromatographic conditions were: oven temperature 162 degrees C, for 14.2 min;
      ramp by 30 degrees C/min to 190 degrees C, for 3.5 min; ramp by 30 degrees C/min
      to 250 degrees C, for 4 min; helium flow rate: 1.7 ml/min; detector and injector
      temperature: 300 degrees C. The sample (1 microl) was injected with a split
      injection technique (split ratio 5:1). MHA recovery was >95% in the 0.5-20
      micromol/l range; the limit of detection was <0.25 micromol/l; day-to-day
      precision, at 2 micromol/l, was Cv<10%. Urinary MHAs were determined in subjects
      exposed to different low-level sources of xylenes: (a) tobacco smoking habit and
      (b) BTX urban air pollution (airborne xylene ranging from 0.1 to 3.7
      micromol/m3). Study (a) showed a significant difference between urinary MHA
      median excretion values of nonsmokers and smokers (4.6 micromol/l vs. 8.1
      micromol/l, p<0.001). Study (b) revealed a significant difference between indoor
      workers and outdoor workers (4.3 micromol/l vs. 6.9 micromol/l, p<0.001), and
      evidenced a relationship between MHAs (y, micromol/mmol creatinine) and airborne
      xylene (x, micromol/m3) (y = 0.085+0.34x; r = 0.82, p<0.001, n = 56). Proposed
      biomarkers could represent reliable tools to study very low-level exposure to
      aromatic hydrocarbons such as those observed in the urban pollution due to
      vehicular traffic or in indoor air quality evaluation.

PMID- 10080638
TI  - Headspace solid-phase microextraction for the determination of benzene, toluene,
      ethylbenzene and xylenes in urine.
AB  - A method for the determination of benzene, toluene, ethylbenzene and xylenes
      (BTEX) in urine of people exposed to these airborne pollutants present in the
      living environment, has been described. Solid-phase microextraction has been used
      for sampling BTEX from the headspace of urine and gas chromatography-mass
      spectrometry has been applied for the selective analysis of chemicals. The method
      has the following features: small volume of urine (2 ml) needed, linearity in the
      range of interest (from the limit of detection up to 5000 ng/l) with coefficient
      of correlation > or =0.998, limit of detection in the range 12-34 ng/l, good
      repeatability (coefficient of variation 2-7%), high specificity. The stability of
      the urine sample during storage (-20 degrees C) was evaluated: BTEX remained
      stable for up to 2 months. The assay has been successfully applied to the
      biological monitoring of two subjects environmentally exposed to airborne BTEX in
      an urban area.

PMID- 10080639
TI  - Improved sample preparation method for selected persistent organochlorine
      pollutants in human serum using solid-phase disk extraction with gas
      chromatographic analysis.
AB  - An improved solid-phase extraction (SPE) method was developed to isolate and
      concentrate trace levels of selected POPs (persistent organochlorine pollutants)
      in human serum prior to GC-MS in SIM mode or GC-ECD quantitation. The extraction
      involves denaturation of serum proteins with formic acid, SPE using C18 Empore
      disk cartridges, followed by elimination of lipid interferences using a sulfuric
      acid wash of the eluate. Use of the SPE disk improved assay throughput and gave a
      cleaner analytical matrix compared with previously reported solid-phase and
      liquid-liquid extraction techniques. The extraction method provided consistent
      recoveries at three fortification levels using 13C12 PCB 149 as internal
      standard. Recoveries ranged from 48 to 140% for organochlorine pesticides (6.25,
      12.5 and 25 ng/ml) and 71 to 126% for polychlorinated biphenyls (0.625, 1.25 and
      2.5 ng/ml).

PMID- 10080640
TI  - Confirmation of multiple sulfonamide residues in bovine milk by gas
      chromatography-positive chemical ionization mass spectrometry.
AB  - Gas chromatography-mass spectrometry (GC-MS) using positive chemical ionization
      was utilized to confirm the presence of 10 ng ml(-1) of nine sulfonamides (SFAs)
      in bovine milk (50 ml). After the addition of a surrogate and hydroxylamine
      hydrochloride, the SFAs are extracted with ethyl acetate followed by cyclohexyl
      solid-phase extraction clean-up. The methylamidotrifluoroacetyl derivatives are
      prepared and analyzed in selected ion monitoring mode. For regulatory
      confirmation, the required specificity was achieved by monitoring the molecular
      ion plus three to five fragment ions for each SFA. Retention times for all SFAs
      were within 0.1 min of their respective standard. The relative ion abundances
      were within 10% of those obtained with standards diluted to the same
      concentration, analyzed on the same day. Concentration was critical, especially
      for the early eluting SFAs, as the enhancement of the relative abundance of the
      parent was more pronounced in extracted samples then in the standards. The
      sensitivity of the mass spectrometer for the different SFAs varied greatly. The
      amount of SFA necessary to obtain spectra that would meet the confirmation
      criteria varied from 25 ng on column for the least sensitive to less than 3 ng
      for the more robust.

PMID- 10080641
TI  - Gas chromatographic method with mass-selective detection for the determination of
      2-isopropoxyphenol in human urine.
AB  - Human metabolism of the insecticide propoxur yields 2-isopropoxyphenol (IPP)
      which is excreted conjugated in urine. In this publication a sensitive and
      selective analytical method is described which permits the determination of IPP
      as a suitable parameter for biomonitoring. The clean-up of the hydrolysed urine
      samples consisted of steam distillation and solid-phase extraction using a
      reversed-phase column. IPP and the internal standard 2-ethoxyphenol were
      converted to their pentafluorobenzyl ethers. Excess of the derivatisation reagent
      was removed using deactivated silica gel. Separation and quantitative analysis
      was carried out by capillary gas chromatography and mass selective detection.
      Coefficients of variation were below 5% for concentrations from 6 to 300
      microg/l. The detection limit was 0.5 microg/l. The method was checked by
      analysing six urine samples from pest controllers after indoor application of
      propoxur. The IPP concentrations ranged from 45 to 306 microg/g creatinine. IPP
      was not detected in urine specimens from 10 non-exposed persons. The sensitivity
      of the developed method permits the detection of latent exposure to propoxur.

PMID- 10080642
TI  - Long-term detection of clenbuterol in human scalp hair by gas chromatography-high
      resolution mass spectrometry.
AB  - A method for the detection of clenbuterol in human scalp hair by gas
      chromatography-high-resolution mass spectrometry (GC-HRMS) is described. The
      sample preparation involved chemical digestion of the protein structure, which
      was achieved by incubating the hair with 1 M KOH at 70 degrees C. A single
      extraction step with tert.-butyl methyl ether provided approximately 90% of the
      analyte, which was dried and derivatized with N-methyl-N
      trimethylsilyltrifluoroacetamide (MSTFA) to yield clenbuterol N,O-bis
      trimethylsilyl (TMS). Hair was collected from four pregnant women who were
      therapeutically treated with Spiropent (clenbuterol-HCl) and from the infant of
      one female patient. Hair samples were taken during the application time and two
      to six months after completion of clenbuterol administration. The detection limit
      of the method was approximately 4 ng clenbuterol/g hair when 25 mg hair material
      were processed and 2 ng/g for 50 mg hair samples (corresponds to 4 pg per
      injection). The method allows clenbuterol to be measured retrospectively for up
      to at least six months. The levels of clenbuterol determined in hair ranged from
      2 to 236 ng/g. No clenbuterol was found in the hair of the infant, which was
      taken five and a half months after delivery. To improve sample preparation, an
      additional purification step via immuno affinity chromatography (IAC) was
      integrated. The IAC purified extracts showed reduced biological background
      interference and an improved limit of detection (0.8 ng/g).

PMID- 10080643
TI  - Evidence for the presence of endogenous 19-norandrosterone in human urine.
AB  - In 1997, in the scope of antidoping control in sport, a not inconsiderable number
      of urine analysed by official laboratories revealed the presence of 19
      nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one) metabolites: 19
      norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19
      noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one). These repeated
      results on a short period of time generated some investigations and especially
      the verification of the possible production of these metabolites by an unknown
      endogenous route in adult entire male. Some experiences were led on different
      persons known to be non-treated with steroids and more precisely with nandrolone.
      Extractive methods were developed focusing on their selectivity, i.e. searching
      to eliminate at best matrix interferences from the target analytes. Gas
      chromatography coupled to mass spectrometry (quadrupole and magnetic instruments)
      was used to detect, identify and quantify the suspected signals. Two types of
      derivatization (TMS and TBDMS), a semi-preparative HPLC as well as co
      chromatography proved unambiguously the presence, in more than 50% of the
      analysed urine (n = 40), of 19-NA at concentrations between 0.05 and 0.60 ng/ml.
      19-NE was not detected with the developed methods (LOD<0.02 ng/ml). Experiments
      led on athletes showed that after a prolonged intense effort, the 19-NA
      concentration can be increased by a factor varying between 2 and 4. Even if some
      complementary researches have to be done in order to determine the maximal
      physiological level of 19-NA and 19-NE, these results should considerably change
      the strategy of antidoping laboratories.

PMID- 10080644
TI  - Analytical methodology for enantiomers of salbutamol in human urine for
      application in doping control.
AB  - Liquid chromatographic procedure with fluorimetric detection for chiral
      separation and quantification of salbutamol enantiomers in urine samples has been
      developed. The extraction of free salbutamol from urine has been considered using
      liquid-liquid and solid-phase procedures. The effect of pH, salting-out effect
      and organic solvent has been studied in liquid-liquid extraction from aqueous and
      urine samples. For solid-phase extraction, different mechanisms (polar, non
      polar, cation-exchange and interactions with a polymeric phase) have been tested
      and the effect of the urine matrix on the extraction recoveries has been
      considered. Bond-Elut Certify extraction cartridges provided the best specificity
      and good recoveries for salbutamol in urine. The sample is acidified, applied to
      the preconditioned cartridges and, after a washing step, salbutamol enantiomers
      are eluted with a mixture of chloroform and 2-propanol (80:20, v/v) containing 2%
      ammonia. Atenolol is used as external standard. Enantioselective separation is
      accomplished with a Chirex 3022 stationary phase (urea type silica-bonded chiral
      phase) using a mobile phase containing hexane-dichloromethane-methanol
      trifluoroacetic acid (250:218:31:1, v/v) and fluorimetric detection with
      excitation and emission wavelengths set at 230 and 309 nm, respectively. The
      method proposed is rapid, selective and sensitive, and seems to be useful to
      differentiate between an authorized and a prohibited use of the drug in doping
      control.

PMID- 10080645
TI  - Validation of an assay for the determination of cotinine and 3-hydroxycotinine in
      human saliva using automated solid-phase extraction and liquid chromatography
      with tandem mass spectrometric detection.
AB  - The validation of a high-performance liquid chromatographic method for the
      simultaneous determination of low level cotinine and 3-hydroxycotinine in human
      saliva is reported. Analytes and deuterated internal standards were extracted
      from saliva samples using automated solid-phase extraction, the columns
      containing a hyper cross-linked styrene-divinylbenzene copolymer sorbent, and
      analysed by reversed-phase liquid chromatography with tandem mass spectrometric
      detection (LC-MS-MS). Lower limits of quantitation of 0.05 and 0.10 ng/ml for
      cotinine and 3-hydroxycotinine, respectively, were achieved. Intra- and inter
      batch precision and accuracy values fell within +/-17% for all quality control
      samples, with the exception of quality control samples prepared at 0.30 ng/ml for
      3-hydroxycotinine (inter-day precision 21.1%). Results from the analysis of
      saliva samples using this assay were consistent with subjects' self-reported
      environmental tobacco smoke (ETS) exposures, enhancing the applicability of
      cotinine as a biomarker for the assessment of low level ETS exposure.

PMID- 10080646
TI  - High sensitivity simultaneous determination in hair of the major constituents of
      ecstasy (3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine and 3,4
      methylene-dioxyethylamphetamine) by high-performance liquid chromatography with
      direct fluorescence detection.
AB  - A simple, but sensitive and specific high-performance liquid chromatographic
      assay for the simultaneous determination of the major constituents of "ecstasy"
      [i.e. 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine
      (MDA), 3,4-methylenedioxyethylamphetamine (MDE)] with direct fluorimetric
      detection, particularly intended for the routine analysis of hair, is described.
      Hair samples (100 mg) were overnight incubated in 1 ml of 0.25 M HCl at 45
      degrees C and extracted with a commercial liquid-liquid method. The dried residue
      reconstituted with 500 microl of 0.05 M NaH2PO4 pH 5.2 was injected. Isocratic
      reversed-phase liquid chromatography was carried out on a column (250x4.6 mm
      I.D.) packed with spherical 5-microm poly(styrene-divinylbenzene) particles; the
      mobile phase was composed of 0.1 M potassium phosphate (pH 3)-acetonitrile
      (82:18). The excitation and the emission wavelengths were set to 285 and 320 nm,
      respectively. Under the described conditions, MDA, MDMA and MDE eluted in
      symmetric peaks with an analysis time of 30 min. The limit of detection was lower
      than 1 ng/ml, with a signal-to-noise ratio of 5, for each compound in solution,
      allowing a cut-off of 0.1 ng/mg in the hair matrix to be established. The intra
      day precision (n = 6) of the assay was characterised by RSDs between 1.0 and 3.0%
      and between 0.52 and 0.88% for concentrations of 10 and 100 ng/ml, respectively;
      in day-to-day precision tests (n = 6), RSDs ranged between 5.12 and 11.12%,
      respectively, for the same concentrations. Interferences from as many as 92
      therapeutic and/or abused drugs currently in use in the population were excluded,
      including N-methyl-1-(3,4-methylenedioxyphenyl)-2 butanamine (MBDB).

PMID- 10080647
TI  - Solid-phase extraction and gas chromatography-mass spectrometry determination of
      kaempferol and quercetin in human urine after consumption of Ginkgo biloba
      tablets.
AB  - A method was developed for the quantification of the flavonoids quercetin and
      kaempferol in human urine using a solid-phase extraction procedure followed by
      gas chromatography-mass spectrometry. Deuterated internal standards of the
      analytes were spiked into the samples prior to extraction. The limit of detection
      of the method was ca. 10 pg on column and precision of the method for
      quantification in a sample of urine was +/-9.40% for kaempferol and +/-7.34% for
      quercetin (n = 6). The levels of quercetin and kaempferol found in urine samples
      were only a small fraction of the amount ingested. The treatment of urine samples
      with beta-glucuronidase markedly increased the levels of flavonoids detected,
      supporting the view that kaempferol and quercetin are eliminated in the urine as
      glucuronides.

PMID- 10080648
TI  - Determination of an ultrashort-acting antihypertensive dihydropyridine,
      clevidipine, in blood using capillary gas chromatography-mass spectrometry and of
      the primary metabolite using liquid chromatography and fluorescence detection.
AB  - A method for the quantitative determination of a new ultrashort-acting
      dihydropyridine, clevidipine (butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-2,6
      dimethyl-1,4-dihydropyridine-3,5-dicarboxyl ate), in whole blood with capillary
      gas chromatography-mass spectrometry with negative ion chemical ionisation is
      presented. The rapidly metabolised drug is stabilised in blood using sodium
      dodecyl sulphate (SDS) which prevents ester hydrolysis. The analytical procedure
      involves liquid-liquid extraction prior to gas chromatographic determination with
      a limit of quantification of 0.5 nmol/l blood. The acidic primary metabolite
      (methyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxyl
      ate), MI, can be determined with liquid chromatography and fluorescence detection
      using a similar sample work-up procedure. Ascorbic acid is then added before
      sampling to prevent oxidation. The limit of quantification for MI is 50 nmol/l
      blood.

PMID- 10080649
TI  - Quantification of 3,4-methylenedioxymetamphetamine and its metabolites in plasma
      and urine by gas chromatography with nitrogen-phosphorus detection.
AB  - A gas chromatographic method with nitrogen-phosphorus detection involving a solid
      liquid extraction phase was developed and validated for the simultaneous
      quantification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4
      methylenedioxyamphetamine (MDA) in plasma. A modification of this method was
      validated for the analysis of MDMA, MDA, 4-hydroxy-3-methoxymethamphetamine
      (HMMA) and, 4-hydroxy-3-methoxyamphetamine (HMA) in urine. Under the analytical
      conditions described, the limits of detection in plasma and urine were less than
      1.6 microg/l and 47 microg/l, respectively, for all the compounds studied. Good
      linearity was observed in the concentration range evaluated in plasma (5-400
      microg/l) and urine (100-2000 microg/l) for all compounds tested. The recoveries
      obtained from plasma were 85.1% and 91.6% for MDMA and MDA, respectively. Urine
      recoveries were higher than 90% for MDMA and MDA, 74% for HMMA, and 64% for HMA.
      Methods have been successfully used in the assessment of plasma and urine
      concentrations of MDMA and its main metabolites in samples from clinical studies
      in healthy volunteers.

PMID- 10080650
TI  - Determination of roxithromycin in human plasma by high-performance liquid
      chromatography with spectrophotometric detection.
AB  - A simple and reproducible method for the determination of roxithromycin in human
      plasma is presented. This method is based on liquid-liquid extraction with hexane
      isoamylalcohol (98:2, v:v) and reversed-phase chromatography with
      spectrophotometric detection at 220 nm. The mobile phase consists of methanol-15
      mM dihydrogen potassium phosphate (70:30, v:v), pH of the aqueous part of the
      mobile phase is 6.0. The column is operated at 60 degrees C. Clarithromycin is
      used as the internal standard. The limit of quantitation is 0.5 microg/ml and the
      calibration curve is linear up to 30 microg/ml. Within-day and between-day
      precision expressed by relative standard deviation is less than 5% and inaccuracy
      does not exceed 9%. The assay was used for pharmacokinetic studies.

PMID- 10080651
TI  - High-performance liquid chromatographic determination of trimebutine and its
      major metabolite, N-monodesmethyl trimebutine, in rat and human plasma.
AB  - A rapid, selective and very sensitive ion-pairing reversed-phase HPLC method was
      developed for the simultaneous determination of trimebutine (TMB) and its major
      metabolite, N-monodesmethyltrimebutine (NDTMB), in rat and human plasma.
      Heptanesulfonate was employed as the ion-pairing agent and verapamil was used as
      the internal standard. The method involved the extraction with a n-hexane
      isopropylalcohol (IPA) mixture (99:1, v/v) followed by back-extraction into 0.1 M
      hydrochloric acid and evaporation to dryness. HPLC analysis was carried out using
      a 4-microm particle size, C18-bonded silica column and water-sodium acetate
      heptanesulfonate-acetonitrile as the mobile phase and UV detection at 267 nm. The
      chromatograms showed good resolution and sensitivity and no interference of
      plasma. The mean recoveries for human plasma were 95.4+/-3.1% for TMB and 89.4+/
      4.1% for NDTMB. The detection limits of TMB and its metabolite, NDTMB, in human
      plasma were 1 and 5 ng/ml, respectively. The calibration curves were linear over
      the concentration range 10-5000 ng/ml for TMB and 25-25000 ng/ml for NDTMB with
      correlation coefficients greater than 0.999 and with within-day or between-day
      coefficients of variation not exceeding 9.4%. This assay procedure was applied to
      the study of metabolite pharmacokinetics of TMB in rat and the human.

PMID- 10080652
TI  - High-performance liquid chromatographic method for determination of tramadol in
      human plasma.
AB  - A modified high-performance chromatographic method using UV detection was
      developed for determination of tramadol concentration in human plasma. Plasma
      samples were extracted with ethyl acetate in a one-step liquid-liquid extraction
      (recovery 88.5+/-2.1%). Analysis of the extract was performed on a reversed-phase
      LiChrospher 60 RP-select B column with a particle size of 5 microm. The mobile
      phase consisted of 0.05 M KH2PO4 aqueous solution (pH 3.5) and acetonitrile in a
      ratio of 90:10 (v/v). Metoprolol was used as the internal standard and UV
      detection at 225 nm was employed. Accuracy of the assay in the concentration
      range examined was from 1.3 to 11.9% for the intra-day run and from 1.4 to 8.1%
      for the inter-day run. The precision of this method varied from 1.2 to 8.7%. The
      reproducibility of the method was determined to be from 0.8 to 7.2% over the six
      day period. A limit of detection was 9 ng/ml at a signal-to-noise ratio of 3.
      This validated method was then applied to the determination of tramadol
      concentrations in healthy volunteers after oral administration of 100 mg of
      tramadol in capsules of Painlax and Tramal.

PMID- 10080653
TI  - Investigation of the in vitro biotransformation of R-(+)-thalidomide by HPLC,
      nano-HPLC, CEC and HPLC--APCI-MS.
AB  - High-performance liquid chromatography (HPLC), nano-HPLC, capillary
      electrochromatography (CEC) and on-line HPLC-atmospheric pressure chemical
      ionization mass spectrometry (APCI-MS) techniques were used for the
      identification and detailed characterization of two new metabolites of the former
      sedative drug thalidomide (TD). The advantages of nano-HPLC and CEC are higher
      peak efficiency and a drastic decrease in the analysis time, which, together with
      lower sample dilution during the analyses, allowed to obtain a detection
      sensitivity that was comparable to HPLC with common-sized columns. Both, nano
      HPLC and CEC could be realized in the commercially available capillary
      electrophoresis system HP3D. On-line HPLC-APCI-MS coupling is a very useful
      technique for the rapid identification of metabolites without any need for
      reference compounds.

PMID- 10080654
TI  - Quantitative determination of albendazole and its main metabolites in plasma.
AB  - Three different and complementary chromatographic methods are described for
      quantitative determination of albendazole (ABZ) and its two main metabolites:
      albendazole sulphoxide (SOABZ) and albendazole sulphone (SO2ABZ). ABZ, SOABZ and
      SO2ABZ can be quantified by two RP-HPLC methods with an ODS2 column and two
      different mobile phases. One of methanol-water (60:40) for ABZ and a second one
      of phosphoric acid in water-acetonitrile (80:20) for SOABZ and SO2ABZ. SOABZ
      bears an asymmetric sulphur centre. Quantitative assay of (+) SOABZ and (-) SOABZ
      can be performed by HPLC. A chiral AGP column and a mobile phase of sodium
      phosphate buffer (8 mM, pH 7.0) containing different amounts of 2-propanol
      between 0 to 2% were used. Pharmacokinetic characteristics of ABZ following oral
      administration of a liquid formulation of ABZ (12 mg/kg) in mice has been studied
      with these three complementary HPLC methods and the results are reported.

PMID- 10080655
TI  - Gas chromatographic-mass spectrometric determination of 4-nonylphenols and 4-tert
      octylphenol in biological samples.
AB  - A simple and rapid method is described for the GC-MS determination of 4
      nonylphenols (NOs) and 4-tert-octylphenol (OC) in biological samples. The NOs and
      OC in the sample are extracted with acetonitrile and the lipid in the sample
      extract is eliminated by partitioning between hexane and acetonitrile. After
      Florisil PR column clean-up, the sample extract is analyzed by GC-MS in the
      selected ion monitoring (SIM) mode. Average recoveries in pale chub (fish) and
      corbicula (shellfish) are 86.0 and 93.4% for NOs, and 95.8 and 96.4% for OC,
      respectively, spiked at the levels of 1.0 microg of NOs and 0.1 microg of OC per
      5 g of fish and shellfish samples. The detection limits are 20 ng/g for NOs and 2
      ng/g for OC.

PMID- 10080656
TI  - Quantitative determination of trimethylamine in urine by solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - Trimethylaminuria (fish odour syndrome) is diagnosed from an increase in urinary
      excretion of trimethylamine with decreased trimethylamine oxide. We report a new
      quantitative stable isotope dilution gas chromatography-mass spectrometry
      procedure for the analysis of these metabolites using solid-phase microextraction
      (SPME). Both polydimethylsiloxane and mixed Carboxen-polydimethylsiloxane SPME
      fibres were found to be suitable for the headspace extraction of TMA. This new
      sampling technique could have wide application for the analysis of volatile and
      semi-volatile compounds by metabolic screening laboratories.

PMID- 10080657
TI  - Persistence of gentian violet and leucogentian violet in channel catfish
      (ictalurus punctatus) muscle after water-borne exposure.
AB  - Gentian violet is a triphenylmethane dye that is an antifungal/antiparastic
      agent. GV is similar to malachite green that has been used in the aquaculture
      industry for treatment or prevention of external fungal and parasitic infections
      in fish and fish eggs although it (MG) is not approved for this use. For these
      reasons, GV's potential for misuse by the aquaculture industry is high. The
      uptake and depletion of gentian violet (GV) were determined in channel catfish
      (Ictalurus punctatus) after water-borne exposure (100 ng ml(-1), 1 h) under
      simulated aquaculture farming conditions. Leucogentian violet (LGV) was rapidly
      formed, concentrated in the muscle tissue, and very slowly eliminated from muscle
      tissue. An isocratic (60% acetonitrile-40% water; 0.05 M ammonium acetate buffer,
      pH 4.5) HPLC system consisting of a 5 microm LC-CN 250x4.6 mm I.D. column, a
      20x2.0 mm I.D. PbO2 oxidative post-column, and a UV-VIS detector set at 588 nm
      were used to determine uptake and depletion of tissue residues of GV and LGV with
      time. GV was rapidly depleted and converted to its major metabolite, LGV, which
      was detected out to 79 days. Therefore, LGV is the appropriate target analyte for
      monitoring exposure of channel catfish to GV.

PMID- 10080658
TI  - Improved high-performance liquid chromatographic assay for nimesulide.
AB  - An improved, validated HPLC assay was developed for the non-steroidal anti
      inflammatory agent, nimesulide. In contrast to previous methods, the present
      assay requires smaller plasma volumes (0.2 ml) and utilizes a commercially
      available, structurally similar analogue of nimesulide, NS-398. The method
      involves a liquid-liquid extraction procedure that can be completed within 4 h,
      followed by reversed-phase HPLC analysis. Briefly, the extraction protocol
      required toluene extraction of acidified plasma samples, followed by back
      extraction of the retained toluene phase with aqueous base. The retained aqueous
      alkaline phase was concentrated by toluene re-extraction. The retained toluene
      phase was evaporated to dryness and reconstituted with 100 microl of mobile
      phase. Extracted samples were injected (50 microl) onto a Shandon Hypersil BDS
      C18 column (5 microm particle size; 250x4.6 mm) equilibrated with 1.0 ml/min of
      68:32 (v/v) methanol-citrate (0.08 M)-phosphate (0.04 M) buffer (pH 3.0) at room
      temperature, with detection at 240 nm. The chromatographic run time was 12 min
      with retention times of 5.9 min and 9.1 min for nimesulide and NS-398,
      respectively. The analytical method was successfully utilized for a pilot
      pharmacokinetic study.

PMID- 10080659
TI  - Determination of plasma phenobarbital concentration by high-performance liquid
      chromatography in rat offspring.
AB  - Plasma phenobarbital (PB) concentrations in rat offspring were determined using a
      9 microl capillary by high-performance liquid chromatography (HPLC). Capillary
      plasma which was put into a Bond Elut cartridge column by using 1 ml of 0.01 M
      KH2PO4 was applied to the column with 50 microl of 2 microg/ml of acetanilide
      (internal standard, I.S.). After washing the column, PB and I.S. were eluted with
      methanol and injected into the HPLC system. There were excellent linear
      correlation between the amount of PB and length of the capillary at three
      different concentrations. Calibration for PB was linear in the range of 0-50
      microg/ml. The coefficients of variation were 3.4-5.0% and 5.9-7.5% in the within
      day and between-day assays, respectively. The extraction recovery rates were 87.5
      105.4%. By this method, it was possible to measure plasma PB concentrations in
      rat offspring without killing. These results suggested that this method is very
      useful to determine the plasma PB concentration derived from mother's milk in
      newborn rats.

PMID- 10080660
TI  - Improved method of determining thiamylal enantiomers in human serum by high
      performance liquid chromatography.
AB  - Thiamylal, a widely used anesthetic drug, has two enantiomers. We developed a
      simple and rapid method for measuring the thiamylal enantiomers in human serum.
      The method involves a liquid-liquid extraction procedure followed by chiral
      resolution using a 5 microm silica-bonded alpha1-acid glycoprotein column (Chiral
      AGP). The thiamylal enantiomers and internal standard were eluted within 15 min
      and were well-resolved. At concentrations of 1, 5 and 20 microg ml(-1), the
      relative standard deviations of R(+)- and S(-)-thiamylal were 1.35-2.88% and 1.37
      3.01%, respectively, for the intra-day assay, and 2.93-4.46% and 2.46-4.84%,
      respectively, for the inter-day assay. This method facilitates the routine
      monitoring and pharmacokinetic studies of thiamylal enantiomers.

PMID- 10080661
TI  - Simultaneous determination of fentanyl and midazolam using high-performance
      liquid chromatography with ultraviolet detection.
AB  - When measuring fentanyl and midazolam simultaneously in the same plasma sample
      with standard high-performance liquid chromatography-ultraviolet (HPLC-UV)
      detection, overlap of the fentanyl peak by the midazolam peak occurs, which makes
      fentanyl determination impossible. We tested the hypothesis that by acidifying
      the methanol mobile phase with 0.02% perchloric acid, 70%, it would be possible
      to separate both peaks. The UV detector was set at 200 nm. Calibration curves for
      fentanyl (range 0-2000 pg/ml) and midazolam (range 0-400 ng/ml) were linear
      (r>0.99). The detection limits were 200 pg/ml (fentanyl) and 10 ng/ml
      (midazolam). Precision and accuracy for intra- and inter-assay variability as
      well as in-line validation with quality control samples (QCS) were acceptable
      (<15 and 20%, respectively), except for fentanyl QCS of 200 pg/ml (17.8%
      precision). Although less sensitive than gas chromatography-mass spectrometry (GC
      MS), reliable measurements of fentanyl, simultaneously with midazolam, can be
      performed with this HPLC-UV system.

PMID- 10080662
TI  - Determination of neostigmine in human plasma and cerebrospinal fluid by high
      performance liquid chromatography with ultraviolet detection.
AB  - A high-performance liquid chromatographic assay coupled with ultraviolet
      detection has been developed for the determination of neostigmine in human plasma
      and cerebrospinal fluid. A novel solid-phase extraction procedure was first used
      for this analyte and allowed good recovery (89+/-4.5%) together with ease and
      speed of execution. The method was sensitive, reproducible (C.V.<4.5%) and
      accurate (100+/-6.6%) over the range 2.6-167.0 ng/ml neostigmine concentrations
      in plasma or cerebrospinal fluid, and was applied successfully to study the
      pharmacokinetics of neostigmine in patients suffering from chronic postoperative
      abdominal pain.

PMID- 10080663
TI  - Sodium peroxydisulfate is a stable and cheap substitute for ammonium
      peroxydisulfate (persulfate) in polyacrylamide gel electrophoresis.

PMID- 10080664
TI  - Does the information level of cancer patients correlate with quality of life? A
      prospective study.
AB  - AIMS AND BACKGROUND: The aim of the study was to evaluate the impact of
      information level on quality of life in cancer patients previously studied for
      their information level. PATIENTS AND METHODS: The information level was
      determined by means of a questionnaire that explored the degree of information on
      diagnosis and status of disease, the patient's interpretation of his/her disease
      status, and his/her satisfaction with the information received. Quality of life
      was evaluated, some months after evaluation of the information level, by means of
      the Functional Living Index for Cancer (FLIC) and the State-Trait Anxiety
      Inventory (STAI 1-2). RESULTS: A total of 175 patients were studied. Information
      was adequate in 53.7% of patients. An adequate level of information was present
      more frequently among patients aged < or = 65 years and in those patients
      followed at a cancer institute. There was no difference in the quality of life of
      adequately versus inadequately informed patients. Satisfaction with the
      information received influenced quality of life in both age groups. Objective
      clinical variables (active disease present and ongoing treatment) negatively
      affected quality of life in patients <65 years, whereas the subjective perception
      of the presence of disease was associated with a worse quality of life in older
      patients. CONCLUSIONS: In the study, although the level of information did not
      affect the quality of life, satisfaction with the information was associated with
      a better quality of life. The finding stresses the importance of a sensible
      disclosure of diagnosis and prognosis.

PMID- 10080665
TI  - A first survey of organized cervical cancer screening programs in Italy. GISCi
      working group on organization and evaluation. Gruppo Italiano Screening
      Citologico.
AB  - In Italy, where no national screening program for cervical cancer exists,
      organized programs have developed on a local basis. We performed the first survey
      of existing organized programs by mailing a standard questionnaire to a large
      network of possibly involved services. For the present survey, a program was
      defined as organized if personal invitations were sent. We identified 29 already
      active organized programs and 4 others in a starting phase. The target population
      of active programs included 2,074,820 women in the age range 25-64 years,
      corresponding to 13.5% of the Italian female population of the same age. The
      situation is rapidly evolving since many regional programs are being implemented.
      Most programs followed Italian and European recommendations as regards the age
      limits, interval between screening rounds, presence of a fail-safe system for
      women referred for colposcopy, presence of protocols for diagnostic workup and
      treatment, and presence of referral centers for such phases. However, many
      programs did not meet national guidelines as regards the size of laboratories
      interpreting smears, which were frequently small. Second-level referral centers
      also frequently had a very small activity. The average (weighted for size of the
      invited population) compliance to invitation and coverage (proportion of women
      with at least one test in the last 3 years) was 32.6% and 66.0%, respectively,
      therefore needing to be improved. Compliance to colposcopy (weighted for number
      of referred women) was 81.4%. We found a very high variability in the proportion
      of women referred for colposcopy that could only be partly explained by different
      referral protocols and could depend on different criteria of smear
      interpretation: the average (weighted for number of tested women) was 2.01%. A
      need for improvement in the process of evaluation and for homogenization of
      criteria of cytology interpretation was identified: work in this regard is on
      going.

PMID- 10080666
TI  - Measurement of the cost of screening for cervical cancer in the district of
      Florence, Italy.
AB  - AIMS AND BACKGROUND: To estimate the cost per woman examined and per CIN II or
      more severe lesion detected in a population-based cytologic screening program for
      cervical cancer prevention. An organized cytologic screening program has been
      ongoing in the Florence District since 1973, and a call-recall system using mail
      invitation has been ongoing since 1980. Smear reading and assessment of screening
      positives is centralized at the screening unit. METHODS AND STUDY DESIGN: All
      relevant resources (costs) consumed by the program were listed and measured. The
      unit cost per examined woman and per each CIN II or more severe lesion detected
      was estimated for each screening phase (recruitment, screening, assessment).
      RESULTS: The cost per examined woman was $24.60, whereas that per CIN II or more
      severe lesion detected was $13,600. Staff accounted for 80% of total amount.
      CONCLUSIONS: Although the cost for a single procedure is low, the cost per
      detected lesion is quite remarkable due to the low detection rate in a population
      screened for a long time. Different approaches and longer interval screening
      tests are discussed.

PMID- 10080667
TI  - The role of radiotherapy in the treatment of carcinoma of the prostate: a survey
      of clinical practices in Lombardy, Italy, by the AIRO-Lombardia Cooperative
      Group. Italian Association for Radiation Oncology.
AB  - AIMS AND BACKGROUND: We report the results of a survey performed in 1994 by the
      AIRO-Lombardia Cooperative Group, on the clinical patterns of radiation treatment
      for prostatic carcinoma in Lombardy, Italy, involving all radiotherapy centers
      serving an overall local population of about 8,800,000 people. METHODS: A
      questionnaire was sent to all 13 radiotherapy centers throughout Lombardy, asking
      for demographic and treatment details concerning the local population of patients
      with a localized (T1-4, N0-1, M0) carcinoma of the prostate treated with
      radiotherapy; 12 centers responded, making the basis for the present report.
      RESULTS: Analysis of collected data showed that in Lombardy: a) approximately 400
      patients per year are irradiated for a localized carcinoma of the prostate,
      accounting for less than 30% of the total expected number of patients with this
      disease presentation; b) a complete staging (with PSA, transrectal
      ultrasonography, abdomino-pelvic CT or MRI scan and total-body bone scan) is
      performed in over 95% of patients before initiating radiotherapy; c) significant
      differences exist between radiotherapy centers as regards treatment planning and
      delivery. CONCLUSIONS: An urgent need exists for implementing procedures aimed at
      standardizing radiotherapy procedures within Lombardy.

PMID- 10080668
TI  - Quality control by portal film analysis in radiotherapy for prostate cancer: a
      comparison between two different institutions and treatment techniques.
AB  - AIMS AND BACKGROUND: Accuracy and reproducibility of patient setup during
      radiotherapy for prostate cancer were investigated in two different Institutions
      (A and B), within their Quality Assurance programs. The purpose of the study was
      to evaluate and compare setup accuracy and reproducibility in Institutions A and
      B, which adopt different patient positioning and treatment techniques for
      prostate irradiation. MATERIALS AND METHODS: A retrospective analysis of portal
      localization films taken during the treatment course was performed: 30 and 21
      patients in Institutes A and B, respectively, entered the study. In Institute A,
      patients were treated in a prone position, utilizing an individualized
      immobilization cast (either an alpha cradle or a heat and vacuum-formed cellulose
      acetate cast) with an open table top and individual abdominal wall compressor to
      minimize small bowel irradiation; a 5-field conformal technique was used. In
      Institute B, patients were treated in a supine position without any
      immobilization device; a 6-field BEV-based technique (conformal only for patients
      treated with a radical aim) was adopted. A total of 598 portal films (420 from
      Institute A and 178 from Institute B) were analyzed. The mean number of films per
      patient was 12 (range, 4-29). Systematic and random setup errors were estimated
      utilizing the statistical method suggested by Bijhold et al. (1992). RESULTS:
      When patients with a mean (systematic) error larger than 5, 8 and 10 mm in
      craniocaudal, lateral and posterior-anterior directions, respectively, were
      compared, no statistically significant difference between the two groups was
      observed. Similarly, when comparing portal films, a significant difference (P
      <0.01) appeared only in the craniocaudal direction (errors > 5 mm: Institute A =
      24%; Institute B = 11%). In both Institutes, the SD of random and systematic
      error distribution ranged from 1.8 to 4.2 mm, with a small prevalence of
      systematic errors. Only for craniocaudal shifts in Institute A was the random
      error larger than the systematic error, and it was significantly worse than in
      Institute B (1 SD, 4.2 mm in Institute A vs 1.8 mm in Institute B). CONCLUSIONS:
      Setup errors observed in Institutes A and B were similar and in accord with data
      reported in the literature. In Institute B, satisfactory geometrical treatment
      quality was achieved without patient immobilization. In Institute A, the goal of
      minimizing small bowel irradiation and prostate motion through the aforementioned
      technique, which makes patient position less comfortable, did not seem to
      considerably increase daily setup uncertainty.

PMID- 10080669
TI  - Brachytherapy for isolated vaginal recurrences from endometrial carcinoma.
AB  - AIMS AND BACKGROUND: Isolated vaginal recurrences of endometrial carcinoma are
      rare, and prognostic factors that predict treatment outcome are still not well
      defined. The aim of the present study was to evaluate the results of
      brachytherapy in isolated vaginal recurrences from endometrial carcinoma.
      METHODS: Thirty-five patients with isolated vaginal recurrences were treated with
      brachytherapy with intravaginal ovoids or cylinders that were calculated to
      deliver 6000 to 7000 cGy at the surface. Patients were assessed for size and
      location of recurrence at presentation, response and complications from therapy.
      RESULTS: Treatment was well tolerated by most patients. Grade 2 toxicity occurred
      in 4 patients (3 cases of partial vaginal stenosis and one proctitis). Complete
      response to radiation was observed in all patients, and an overall 9 failures
      were observed (4 local, 4 distant and 1 local plus distant). Twenty patients
      (57%) were alive without evidence of disease at 3 to 11 years following
      treatment. Site of vaginal recurrence (upper third versus others) and long (more
      than 12 months versus less than 12 months) interval from hysterectomy were the
      only factors significantly related to local failures. CONCLUSIONS: Isolated
      vaginal recurrences following hysterectomy for endometrial carcinoma can be
      treated with brachytherapy with a low rate of severe toxicity.

PMID- 10080670
TI  - Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant
      chemotherapy alone in premenopausal breast cancer patients with positive axillary
      nodes.
AB  - AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with
      adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall
      survival (OS), overall disease-free survival (ODFS), local disease-free survival
      (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed
      retrospectively two non-randomized groups of premenopausal high-risk breast
      cancer patients treated from 1985 to 1990 in the following Institutions:
      Department of Radiation Oncology of Brescia University, "Istituto del Radio O.
      Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta
      Foundation" (BF). A total of 163 patients was found to satisfy the criteria of
      the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles
      CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and
      chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at
      IRA to avoid the feared increase in toxicity due to the association with RT.
      Primary surgical treatment was modified radical mastectomy with axillary node
      dissection in both cases. RESULTS: A statistically significant improvement in OS
      was found in systemic adjuvant therapy patients compared to those also given RT
      (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was
      found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P
      = 0.46. A statistically significant improvement in LDFS at 5 years was found in
      irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved,
      although without evidence of statistical significance, in the CMF(1-8) group: at
      5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces
      the risk of local recurrence but without a statistically significant reduction in
      mortality. The lack of a survival benefit may somehow reflect the dose reduction
      in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the
      CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose
      intensity of CMF in this setting may also be important. In fact, although many
      CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received
      a dose intensity higher than the maximum one of the CMF(1-21) patients. Although
      our results should be interpreted with caution, they seem to provide further
      rationale for testing the association of postoperative radiotherapy and the CMF(1
      8) regimen in stage II breast cancer with positive nodes and treated with
      demolitive surgery, as already done in the conservative management of breast
      cancer, also in view of the new support therapies now available (i.e. hematologic
      growth factors).

PMID- 10080671
TI  - Ifosfamide bolus followed by five days continuous infusion in extensively
      pretreated patients with advanced breast cancer: a phase II study.
AB  - PURPOSE: A phase II study with ifosfamide in pretreated patients with advanced
      breast cancer was performed to determine the objective response rate, the
      toxicity and the feasibility of the regimen. METHODS & STUDY DESIGN: Patients
      enrolled had advanced breast cancer pretreated with at least one previous regimen
      of chemotherapy for advanced disease. Treatment consisted of ifosfamide infused
      at a dose of 2 g/m2 iv in 4 hrs followed by ifosfamide, 8 g/m2 iv in 120 hrs in
      ambulatory treatment, using a portable external pump system. The total dose of
      ifosfamide was 10 g/m2; mesna (4 g/m2 iv) was administered mixed with ifosfamide
      in 120 hrs Cycles were repeated every 3 weeks. Three patients were pretreated
      with neoadjuvant and 15 with adjuvant chemotherapy. All patients were treated for
      advanced disease (median number of regimens, 1; range, 1-3): 21 with the
      cyclophosphamide-containing regimen and 15 with adryamicin. Sixteen patients
      received one or more lines of endocrine therapy. Fifteen patients had dominant
      site in viscera, 6 in bone, and only one in soft tissue; 17 patients had more
      than one site of disease. RESULTS: Twenty-two patients were enrolled and all were
      assessable for response and toxicity. A partial response was reached in 5
      patients (23%; 95% confidence limits 5% to 60%). Hematologic toxicity was the
      dose-limiting side effect; grade 4 leukopenia occurred in 10 patients (46%).
      CONCLUSIONS: Considering the response rate obtained in our series of intensively
      pretreated patients, the results seem to indicate that the regimen is active and
      could be included among the possible options in the treatment of patients with
      refractory, poor-prognosis, advanced breast carcinoma.

PMID- 10080672
TI  - Increasing doses of 5-fluorouracil and high-dose folinic acid in the treatment of
      metastatic colorectal cancer.
AB  - AIMS AND BACKGROUND: Combined 5-fluorouracil (5FU) and folinic acid (FA) is the
      first-line treatment of metastatic colorectal cancer. The aims of this study were
      to individualize the dose of 5FU in a weekly schedule in which the maximum
      tolerated dose of 5FU is administered to each patient, and to evaluate the impact
      of increasing 5FU doses on response and survival. METHODS: Thirty-two patients
      (30 evaluable for response) with metastatic colorectal cancer were treated with
      weekly intravenous doses of FA 150 mg/m2 and a fast infusion of 5FU, at an
      initial dose of 600 mg/m2 which was increased by 60 mg/m2 every week until the
      appearance of a side effect, in order to determine the maximum tolerated dose for
      the patient. RESULTS: We obtained 11 objective responses (36.7%, median survival
      22 months) and 15 disease stabilizations (50%, median survival 15 months); there
      were four cases of progressive disease (13.3%, median survival 4 months). The
      overall survival was 15 months. Twenty-eight patients (87.5%) tolerated 5FU doses
      of 720 mg/m2 or more. CONCLUSIONS: Weekly 5FU with high-dose FA modulation can be
      individualized by dose escalation. A 5FU dose of 720 mg/m2 per week seems to be
      critical, as higher doses are no more effective and lead to severe side effects.
      This schedule gives good results in terms of response, even though the complete
      response rate remains low.

PMID- 10080673
TI  - Suramin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in
      metastatic colorectal cancer patients resistant to 5-FU+LV-based chemotherapy.
AB  - AIMS AND BACKGROUND: Suramin has been shown to be of interest as a potential new
      anticancer agent because of its capacity to inhibit the binding of several growth
      factors to their receptors and to inhibit the growth of cancer cells in vitro.
      Since multi-autocrine loops involving growth factors which are antagonized by
      suramin have been demonstrated in colorectal cancer, we previously evaluated the
      activity of suramin in patients with advanced colorectal cancer. Interestingly,
      in this study three patients who had received 5-FU+LV after suramin, although
      heavily pretreated with fluoropyrimidines, obtained an objective response. This
      observation was intriguing as it might have been that suramin had changed the
      biology of the tumor, making it sensitive to 5-FU+LV. We therefore conducted the
      present study to investigate the possibility that suramin might overcome the
      resistance to 5-FU+LV. METHODS AND STUDY DESIGN: Only colorectal cancer patients
      with metastatic and progressive disease during 5-FU+LV-based chemotherapy were
      eligible for this study. Suramin was administered for eight weeks at doses
      determined by means of a computer-assisted dosing algorithm that used Bayesian
      pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/ml.
      5-FU was administered weekly at a dosis of 450 mg/m2 halfway through a two-hour
      infusion of I-LV 250 mg/m2 starting one week after the initiation of suramin for
      a maximum of 26 weeks. RESULTS: Treatment was relatively well tolerated, but no
      objective responses were observed after the accrual of 13 patients in the first
      stage of the trial. Consequently, the trial was interrupted according to the
      initial two-stage sampling design. CONCLUSIONS: The present study does not
      support the hypothesis that suramin might overcome resistance to 5-FU+LV and its
      use in colorectal cancer is not recommended.

PMID- 10080674
TI  - Phase II study of the activity and tolerability of a combined regimen of high
      dose epirubicin and cisplatin in stage IIIb and IV non-small cell lung cancer.
AB  - AIM: To explore the feasibility and activity of a combined regimen of high-dose
      epirubicin and cisplatin as an alternative to current treatments for non-small
      cell lung cancer (NSCLC). METHOD: Forty-four patients with stage IIIb or IV
      NSCLC, median Karnofsky index 90, were enrolled. Epirubicin (60 mg/m2) was
      administered on days 1 and 2 and cisplatin (100 mg/m2) on day 1. Treatment was
      repeated every 21 days for a maximum of six cycles. A hematopoietic growth factor
      (G-CSF) was used only for patients reaching codified nadir count values. RESULTS:
      A total of 130 cycles were administered with a mean of 2.9 cycles per patient. Of
      41 assessable patients one showed a complete response and 15 had partial
      responses (overall response rate, 39%). Grade 3 or 4 leukopenia and grade 3
      hemoglobin toxicity were seen in 40% and 14%, respectively, of the administered
      cycles. The most common nonhematologic toxic events were nausea and vomiting,
      mucositis, anorexia, and asthenia. CONCLUSIONS: This epirubicin-cisplatin regimen
      seemed effective and was generally well tolerated, and therefore suitable for use
      in an outpatient setting.

PMID- 10080675
TI  - Activity and tolerability of courses of intra-arterial chemotherapy followed by
      chemoembolization in unresectable hepatocellular carcinoma.
AB  - AIMS AND BACKGROUND: We previously reported encouraging response rates and
      survival with combined intra-arterial (i.a.) chemotherapy and chemoembolization
      in unresectable hepatocellular carcinoma. We therefore evaluated a new program
      combining three courses of i.a. chemotherapy with chemoembolization administered
      every 28 days. PATIENTS AND METHODS: The treatment regimen consisted of L
      leucovorin (100 mg/m2 i.v.), fluorouracil (800 mg/m2 i.a.), and carboplatin (250
      mg/m2 i.a.). Chemoembolization with mitoxantrone (10 mg/m2) plus ethiodized oil
      and gelatin sponge was performed immediately after. The same treatment was given
      every 28 days for 3 times. RESULTS: Twenty-eight patients entered the study and
      were assessable for response and side effects. There were 24 males and 4 females
      (median age, 68 yrs; range, 42-75). TNM stage was II-III in 20 and IVA in 8; 17
      were Child's A and 11 Child's B. Baseline alpha-fetoprotein was elevated in 15,
      and there was cirrhosis in 23. Twelve patients had a partial response (43%; 95%
      confidence interval, 24-63%), 13 had stabilization, and 3 progressive disease.
      Median survival was 16.6 months (range, 2-24). Sixteen patients had grade I-II
      pain and 14 grade I-II fever. CONCLUSIONS: Our results indicate that the regimen
      is safe and well tolerated. Despite 43% objective remissions, our results do not
      seem better than those obtained with less intensive regimens.

PMID- 10080676
TI  - Pilot study of daily ifosfamide 1 g/m2 until grade III granulocytopenia as second
      line chemotherapy for anthracycline-pretreated advanced soft tissue sarcoma.
AB  - BACKGROUND AND AIMS: Second-line chemotherapy regimens for advanced soft tissue
      sarcomas after treatment failure or tumor relapse following anthracyclines are
      still investigational. The aim of the present study was to assess the activity of
      ifosfamide with a new schedule for patients with advanced soft tissue sarcoma
      failing to achieve remission or relapsing following anthracycline-containing
      regimens; it was attempted to individualize dosages and prevent excessive
      toxicity. STUDY DESIGN: A second-line chemotherapy regimen of ifosfamide 1 g/m2
      daily, with drug withdrawal until the next cycle upon appearance of grade III
      granulocytopenia, was administered to 21 patients with advanced soft tissue
      sarcoma. All patients failed to achieve remission or relapsed following a first
      line high-dose anthracycline regimen (epirubicin 180 mg/m2 or zorubicin 600 mg/m2
      per cycle). The cycles were repeated every four weeks. RESULTS: The median number
      of cycles applied was three (range, 1-15). The ifosfamide dosage reached was 4-13
      g/m2 per cycle, median 5 g/m2. A complete response was achieved in 1/21 patient
      (5%), no partial responses were observed, 4/21 patients (20%) had stable disease,
      and 16/21 (75%) had progressive disease. No difference in response and stable
      disease rates was observed between responders and non-responders to first-line
      chemotherapy. No difference in the ifosfamide dose reached was noted between
      patients receiving second-line chemotherapy directly following first-line therapy
      and those with a time interval between first- and second-line chemotherapy. The
      granulocytopenia grade III nadir lasted for a median of one day (range, 1-3) and
      other toxicities including hematological toxicity were mild and infrequent.
      CONCLUSIONS: In view of the swift regeneration from grade III granulocytopenia,
      continuation of the study with granulocytopenia grade IV as a limiting factor for
      ifosfamide dose escalation seems feasible, with the prospect of better efficacy
      without excessive toxicity.

PMID- 10080677
TI  - Nutritional support in patients with cancer of the esophagus: impact on
      nutritional status, patient compliance to therapy, and survival.
AB  - AIMS AND BACKGROUND: The multimodal approach to patients with esophageal squamous
      cell carcinoma often includes polychemotherapy combined with radiation therapy.
      Cancer dysphagia and drug-related anorexia, mucositis and vomiting can all lead
      to malnutrition. The aim of this study was to analyze the impact of the
      administration of enteral nutrition (EN) on the patient's nutritional status,
      tolerance of chemotherapy and radiotherapy, and final oncological outcome.
      METHODS: Fifty esophageal cancer patients who were to be submitted to
      chemotherapy (days 1-4 5-fluorouracil (FU) 1 g/m2/day and cisplatin (CDDP) 100
      mg/m2/day 1) for two cycles plus radiotherapy (31 Gy) were referred to the
      Nutrition Support Unit prior to any therapy due to their malnourished status.
      Twenty-nine dysphagic patients received nutrition via tube (37 kcal/kg/day + 2.0
      g proteins/kg/day for 34 days), while 21 others who were not dysphagic were given
      a standard oral diet (SD). The patients who received EN had a more severe weight
      loss than the SD patients (16.8% vs 12.8%, P <0.02). RESULTS: The dose of
      administered EN represented 86% of the planned support, and 70% of the
      nutritional therapy was administered in the home setting. Administration of EN
      support resulted in stable body weight and unchanged levels of visceral proteins,
      while SD patients had a decrease in body weight, total proteins and serum albumin
      (P <0.01). There was no difference between the two groups in terms of tolerance
      and response to cancer therapy, suitability for radical resection and median
      survival (9.5 months). CONCLUSIONS: EN in patients with cancer of the esophagus
      undergoing chemotherapy and radiotherapy is well tolerated, feasible even in the
      home setting, prevents further nutritional deterioration and achieves the same
      oncological results in dysphagic patients as those achieved in non-dysphagic
      patients.

PMID- 10080678
TI  - Changes in serum lipid and lipoprotein levels in postmenopausal patients with
      node-positive breast cancer treated with tamoxifen.
AB  - Tamoxifen has been used for a long time as an adjuvant hormonal treatment in
      breast cancer patients. We studied 62 newly diagnosed postmenopausal women, aged
      50-79 years, with node-positive breast cancer and receiving adjuvant tamoxifen
      (20 mg per day). Total serum cholesterol, triglycerides, HDL-cholesterol, LDL
      cholesterol, VLDL-cholesterol, apo AI, apo AII, apo B and Lp(a) were determined
      before the surgery and 3, 6, 9, 12 and 24 months after starting tamoxifen
      treatment. Tamoxifen significantly reduced total serum cholesterol (6.13+/-1.20
      mmol/L vs 5.21+/-1.05 mmol/L) (P <0.01), LDL-cholesterol (3.72+/-0.70 mmol/L vs
      2.93+/-0.51) (P <0.01) and Lp(a) (0.11+/-0.07 g/L vs 0.02+/-0.01 g/L) (P < 0.01).
      There were no changes in triglycerides or HDL-cholesterol serum levels during
      tamoxifen treatment. The results indicate that an additional beneficial effect of
      adjuvant tamoxifen therapy may be that it decreases cardiovascular risk in such
      patients.

PMID- 10080679
TI  - pS2 in breast carcinoma: association with steroid hormone receptor status.
AB  - AIMS AND BACKGROUND: Knowledge of the steroid hormone receptors has proved to be
      of significant value in breast cancer. In the present study the possible
      importance of estrogen-regulated pS2 protein was investigated. Our direct purpose
      was to answer the question whether the expression of pS2 may be a marker of
      functional heterogeneity with respect to the steroid hormone receptor status.
      METHODS AND STUDY DESIGN: The study included 152 patients with primary, operable,
      histologically confirmed breast carcinomas. Histology specimens were reviewed and
      classified according to type, nodal status, tumor size and grade. Steroid hormone
      receptors were assayed by biochemical methods according to the procedures
      recommended by the EORTC. pS2 protein measurement was performed in breast
      carcinoma cytosols using an immunoradiometric assay. The results were analyzed by
      non-parametric statistical methods. RESULTS: A statistically significant inverse
      correlation between pS2 protein expression and histological tumor grade was
      found. The expression of pS2 protein was confirmed to be correlated with steroid
      hormone receptor status. However, it is important to point out that in spite of
      these statistically significant findings there were no significant biological
      associations due to overlapping individual pS2 protein values. The baseline level
      of expression of pS2 protein was obtained in histological grade III carcinomas
      with a negative steroid hormone receptor status. It was shown that the
      distribution of carcinomas according to the baseline level of pS2 protein
      expression was heterogeneous among estrogen receptor-positive carcinomas, and
      strikingly homogeneous among estrogen and progesterone-negative carcinoma.
      CONCLUSION: Our study suggested that PR and pS2 protein may identify distinct
      subsets of estrogen receptor-positive breast carcinomas.

PMID- 10080680
TI  - CD30 differential staining is useful in classifying lymphomas intermediate
      between Hodgkin's disease and anaplastic large cell (Ki1) lymphoma.
AB  - AIMS AND BACKGROUND: The authors analyzed the BerH2 reactivity patterns of the
      tumor cells in 23 Hodgkin's lymphomas (HD), in 13 CD30+ anaplastic large cell
      (Ki1) lymphomas (ALCL), in two HD with transition to secondary CD30+ ALCL, and in
      six additional lymphomas intermediate between HD and ALCL. METHODS: Paraffin
      blocks of formalin-fixed biopsies were immunostained. Immunostaining was modified
      by pronase digestion and by microwave assistance. RESULTS: Hodgkin-Reed-Sternberg
      (HRS) cells of all 23 Hodgkin's lymphomas were reactive for BerH2, but the
      reactivity patterns differed: after pronase digestion, HRS cells of 17/23
      Hodgkin's lymphomas showed exclusively or at least predominantly cytoplasmic
      BerH2 reactivity, whereas only four Hodgkin's lymphomas presented with prominent
      membrane-bound positivity. Microwave processing in 16/23 Hodgkin's lymphomas
      induced membrane-bound BerH2 positivity in the HRS cells; a minority of five
      cases retained the distinct cytoplasmic pattern. In contrast, 10/13 ALCLs were
      characterized by membranous reactions, independent of whether pronase or
      microwave pretreatment had been applied. The CD30+ ALCLs secondary to HD also
      showed a tendency towards membranous positivity more than did the antecedent
      Hodgkin's lymphomas. In the HD/ALCL borderline group, 3/6 cases revealed
      cytoplasmic BerH2 patterns after pronase digestion and thus were more closely
      related to HD, whereas 2/6 cases reacted with membranous positivity as did the
      genuine ALCLs of our series. CONCLUSIONS: We conclude from these findings that
      the above modifications in CD30 immunostaining can be helpful in the
      characterization of lymphomas that constitute a continuous histomorphological as
      well as phenotypical spectrum between HD and ALCL.

PMID- 10080681
TI  - Accuracy of epiluminescence microscopy among practical dermatologists: a study
      from the Emilia-Romagna region of Italy.
AB  - AIMS AND BACKGROUND: The accuracy of epiluminescence microscopy (ELM) for
      pigmented skin lesions (PSLs) is still unclear. The large scale utilization of
      the technique is generally discouraged. The present study was aimed at comparing
      the accuracy of ELM with that of clinical examination alone in a group of 20
      practical dermatologists. METHODS AND STUDY DESIGN: Thirty digital clinical
      images of benign and malignant PSLs and their digital ELM counterparts were used.
      A set of cumulative accuracy measures reported in the combined clinical/ELM
      diagnosis was compared with that reported in the clinical diagnosis alone.
      RESULTS: The proportion of nonmelanocytic lesions (NMLs), melanocytic nevi, and
      melanomas correctly identified, the predictive value of such diagnoses, and the
      proportion of melanomas detected by referral for biopsy (irrespective of the
      diagnosis reported) increased significantly. The cases referred for biopsy
      despite a "benign" impression decreased significantly among NMLs. CONCLUSIONS:
      The observed tendency towards a greater accuracy suggests that even in the
      routine dermatology practice ELM has the potential to improve the clinical
      examination of PSLs.

PMID- 10080682
TI  - Pharmacokinetics of intraperitoneal gemcitabine in a rat model.
AB  - BACKGROUND: Gemcitabine (2'-2' difluorodeoxycytidine) has been shown to possess a
      broad spectrum of antitumor activity against various malignancies, particularly
      pancreatic carcinoma. For cancers occurring within the abdominal cavity, the
      advantage of intraperitoneal (i.p.) chemotherapy over intravenous (i.v.)
      chemotherapy is the high drug concentration that can be achieved locally. In
      addition, the cytotoxic effect of several anticancer agents can be enhanced by
      hyperthermia. Using a rat model, this study was designed to compare i.p. vs i.v.
      gemcitabine and to evaluate the effect of hyperthermia on i.p. gemcitabine.
      METHODS: In the first phase of this study, 18 Sprague Dawley rats were given a
      single dose of gemcitabine then randomized into three groups according to dose
      and route of delivery of chemotherapy (12.5 mg/kg--i.v., 12.5 mg/kg--i.p. or 125
      mg/kg--i.p.). In a separate experiment (phase 2), 12 Sprague Dawley rats were
      given a continuous i.p. perfusion of gemcitabine (12.5 mg/kg in 150 mL total
      perfusate) and randomized into two groups according to the temperature of the
      peritoneal perfusate (normothermic or hyperthermic). During the course of both
      experiments, peritoneal fluid and blood were sampled using a standardized
      protocol. At the end of the procedure the rats were sacrificed and all urine was
      extracted. Selected tissue samples were taken from rats in the second phase of
      the study. The concentration of gemcitabine in all samples was determined by high
      performance liquid chromatography (HPLC). RESULTS: When gemcitabine was delivered
      at 12.5 mg/kg (phase 1) the area under the curve (AUC) was significantly higher
      with i.p. administration as compared to i.v. administration (P = 0.001). The AUC
      ratio (AUC peritoneal fluid/AUC plasma) was 12.5+/-3.2 for i.p. delivery as
      opposed to 0.2+/-0.2 for i.v. delivery (P = 0.0002). The AUC ratio for i.p.
      gemcitabine at 125 mg/kg was 26.8+/-5.8. Although there was no significant
      difference in drug concentrations between samples from the normothermic and
      hyperthermic groups, all tissue samples (except stomach) in the hyperthermic
      group exhibited increased gemcitabine concentrations. CONCLUSION: These
      experiments demonstrated that the exposure of peritoneal surfaces to gemcitabine
      is significantly increased with i.p. gemcitabine. Intraabdominal hyperthermia had
      no significant effect on the pharmacokinetics of i.p. gemcitabine but there was
      evidence of increased absorption of gemcitabine in most intraabdominal tissues.
      Due to the likelihood of a high incidence of microscopic residual disease after
      resection of a pancreatic carcinoma, clinical studies to evaluate i.p.
      hyperthermic gemcitabine may be indicated.

PMID- 10080683
TI  - Solitary eosinophilic granuloma of the calvaria.
AB  - AIMS AND BACKGROUND: Histiocytosis X is a condition characterized by an abnormal
      proliferation of histiocytes with a variable granulomatous and inflammatory
      component; bone involvement is almost always present. The aim of this study was
      to define the management of solitary eosinophilic granuloma (EG) of the calvaria
      in adult patients, in relation to the size and site of the lesion. METHODS:
      Fourteen patients, ranging in age from 7 to 45 years, with solitary eosinophilic
      granuloma of the calvaria were surgically treated by craniectomy or curettage and
      cranioplasty. We subgrouped the lesions into two types: A) lesions localized
      inside the diploe and/or compressing the cerebral parenchyma below but without
      dural infiltration; B) lesions with mainly intracranial growth, compressing the
      cerebral parenchyma and infiltrating the dura. The infiltrated dura mater in type
      B lesions was replaced with a dural patch. Cranioplasty was performed in lesions
      with a diameter of 4 cm or more and/or located in aesthetically exposed areas of
      the skull. RESULTS: None of the patients died during the study and no local or
      systemic recurrences were observed during follow-up (min. 3 yrs, max. 8 yrs).
      CONCLUSIONS: Surgical treatment of patients with isolated EG of the calvaria not
      only is simple and quick but also allows histological diagnosis of the osteolytic
      lesion. These patients do not require further adjuvant treatment. Cranioplasty
      should be performed when the lesion has a diameter of 4 cm or more, when it is
      located in aesthetically exposed areas of the skull such as the frontal or
      temporal bones, or when it produces alterations of the normal skull morphology.

PMID- 10080684
TI  - Villoglandular papillary adenocarcinoma of the uterine cervix: report of a case.
AB  - Villoglandular papillary adenocarcinoma is a recently described form of
      adenocarcinoma of the uterine cervix, which apparently affects young women and
      seems to have a favorable course with an excellent prognosis. We report on a case
      of villoglandular papillary adenocarcinoma in a 26-year-old woman. The patient
      was treated by conization alone and is disease free after a 40-month follow-up.

PMID- 10080685
TI  - Dehydroepiandrosterone sulfate, estradiol and non-protein-bound estradiol serum
      concentrations in postmenopausal women with and without breast disease.

PMID- 10080686
TI  - [Tamoxifen and breast cancer: is everything known already?].

PMID- 10080687
TI  - [4th International Conference of Geriatric Oncology. Cancer in the Elderly].

PMID- 10080688
TI  - Cloning, expression and N-terminal myristoylation of CpCPK1, a calcium-dependent
      protein kinase from zucchini (Cucurbita pepo L.).
AB  - We have isolated a full-length cDNA clone (CpCDPK1) encoding a calcium-dependent
      protein kinase (CDPK) gene from zucchini (Cucurbita pepo L.). The predicted amino
      acid sequence of the cDNA shows a remarkably high degree of similarity to members
      of the CDPK gene family from Arabidopsis thaliana, especially AtCPK1 and AtCPK2.
      Northern analysis of steady-state mRNA levels for CpCPK1 in etiolated and light
      grown zucchini seedlings shows that the transcript is most abundant in etiolated
      hypocotyls and overall expression is suppressed by light. As described for other
      members of the CDPK gene family from different species, the CpCPK1 clone has a
      putative N-terminal myristoylation sequence. In this study, site-directed
      mutagenesis and an in vitro coupled transcription/translation system were used to
      demonstrate that the protein encoded by this cDNA is specifically myristoylated
      by a plant N-myristoyl transferase. This is the first demonstration of
      myristoylation of a CDPK protein which may contribute to the mechanism by which
      this protein is localized to the plasma membrane.

PMID- 10080689
TI  - A multi-responsive gene encoding 1-aminocyclopropane-1-carboxylate synthase
      (ACS6) in mature Arabidopsis leaves.
AB  - Physiological and biochemical studies have provided evidence that mechanical
      strain (touch)-induced modifications in plant growth and development may be due
      to ethylene. In order to better understand the involvement of ethylene in touch
      induced responses, we identified and characterized an Arabidopsis cDNA (ACS6)
      encoding 1-aminocyclopropane-1-carboxylic acid (ACC) synthase which is an
      important regulatory enzyme in the ethylene biosynthetic pathway. Northern
      analysis showed that ACS6 was induced by touch in the leaves of 3-week old light
      grown plants within 5 min and reached maximum transcription at 15 min. ACC, which
      is the product of ACC synthase and the immediate precursor to ethylene, exhibited
      a dramatic rise between 15 and 30 min after touch stimulation. Experiments with
      multiple touch treatments showed that a saturation in gene expression was
      obtained with one touch treatment and subsequent touch stimulations were
      progressively less effective in promoting ACS6 expression. Additional
      characterization of ACS6 gene expression indicated that the gene is also induced
      by wounding, and by treatment with LiCl, NaCl, CuCl2, auxin, cycloheximide (CHX),
      aminooxyacetic acid (AOA) and ethylene. ACC levels were also increased in
      response to each of these treatments with the exception of CHX and AOA which
      resulted in a decrease and no effect, respectively. Our results show that ACS6 is
      rapidly turned on in response to touch which is followed by an increase in ACC
      which is the immediate precursor to ethylene, thereby providing evidence that it
      is responsible for touch-inducible ethylene production in light-grown Arabidopsis
      plants. The identification and characterization of ACS6 now provides us with a
      tool to better understand the involvement of ethylene produced in response to
      external stimuli as well as during plant growth and development.

PMID- 10080690
TI  - Characterization of a pine multigene family containing elicitor-responsive
      stilbene synthase genes.
AB  - Young pine seedlings respond to environmental stress by induced synthesis of
      pinosylvin, a stilbene phytoalexin. Heartwood of pine trees is characterized by a
      high content of pinosylvin. The formation of pinosylvin from cinnamoyl-CoA and
      three molecules malonyl-CoA catalysed by pinosylvin synthase is typical of the
      genus Pinus. Its enzyme activity not detectable in unstressed seedlings is
      substantially increased upon application of stimuli like UV-light or infection
      with the phytopathogenic fungus Botrytis cinerea. A genomic DNA library was
      screened with pinosylvin synthase cDNA pSP-54 as a probe. Ten clones were
      isolated and grouped into five subclasses according to the size of their introns.
      After subcloning into plasmid T7T3, four different members of the five gene
      subclasses were characterized by sequencing. Emphasis was put on isolating
      various promoters and analyzing and comparing their responsiveness. The amino
      acid sequences deduced from genes PST-1, PST-2, PST-3 and PST-5 shared an overall
      identity of more than 95%. In gene PST-5, the putative translation start site ATG
      was replaced by CTG. While promoter regions near the TATAA box were almost
      identical PST-1, PST-2 and PST-3, further upstream sequences differed
      substantially. Differences in promoter strength were analysed both in transgenic
      tobacco plants and by transient expression in tobacco protoplasts. Constructs
      used contained the bacterial beta-glucuronidase under the control of the
      promoters of pine genes PST-1, PST-2 and PST-3. Upon treatment with UV light or
      fungal elicitor, the promoter of PST-1 showed highest responsiveness and led to
      tissue-specific expression in vascular bundles. The data suggest that in pine the
      gene product of PST-1 is responsible for both the stress response in seedlings
      and pinosylvin formation in the heartwood.

PMID- 10080691
TI  - Photoregulated expression of the PsPK3 and PsPK5 genes in pea seedlings.
AB  - The PsPK3 and PsPK5 genes of the garden pea encode protein-serine/threonine
      kinases whose catalytic domains are closely related to known signal transducing
      kinases from animals and fungi. The PsPK3 polypeptide is predicted to be located
      in the nucleus, whereas PsPK5 is a homologue of NPH1, the probable blue light
      receptor for phototropism from Arabidopsis. We found previously that when
      etiolated pea seedlings are illuminated with continuous white light, PsPK3 and
      PsPK5 transcript levels within apical buds decline substantially, reaching their
      minimum levels within one day of exposure to light. The role of light in
      regulating the expression of the PsPK3 and PsPK5 genes was investigated further.
      To gain insight into the rapidity with which expression changes, 6-day old, dark
      grown pea seedlings were transferred to continuous white light, and PsPK3 and
      PsPK5 RNA levels monitored over the ensuing 24 h. While transcripts from the RbcS
      gene family increase, the PsPK3 and PsPK5 mRNAs decline rapidly to their minimum
      levels. PsPK5 mRNA declines 10-fold in ca. 2 h, whereas PsPK3 mRNA declines 4
      fold in ca. 8 h. We used single pulses of light to elucidate which photoreceptor
      triggers the negative regulation of PsPK3 and PsPK5 gene expression. To assess
      phytochrome involvement, etiolated seedlings were treated with single pulses of
      red light, red followed by far-red light, or far-red light alone. RbcS induction
      by a red light pulse is reversible with a subsequent far-red light pulse, clearly
      showing that phytochrome mediates its induction. Likewise, RbcS expression is
      induced with a single pulse of blue light or a dichromatic pulse of red+blue
      light. However, none of these pulses trigger the PsPK3 and PsPK5 mRNA levels to
      decline. Given the lack of effectiveness of light pulses, etiolated seedlings
      were transferred to continuous light of three different qualities to determine
      the spectral sensitivity of PsPK3 and PsPK5 gene expression. Exposure to
      continuous red, continuous far-red, or continuous blue light causes the PsPK3 and
      PsPK5 mRNAs to decline and transcripts from the RbcS and Cab gene families to
      increase. One likely explanation is that phytochrome A mediates the responses of
      these genes to continuous far-red light. The effectiveness of continuous red
      light and blue light in triggering the reduction in PsPK3 and PsPK5 mRNA levels
      and the increase in RbcS and Cab mRNAs may imply the participation of additional
      phytochromes and/or cryptochromes. Thus, the PsPK3 and PsPK5 genes exhibit
      responsiveness to continuous light, but a lack of responsiveness to single light
      pulses that is unusual, and perhaps unique, among light-regulated genes.

PMID- 10080692
TI  - S1 SINE retroposons are methylated at symmetrical and non-symmetrical positions
      in Brassica napus: identification of a preferred target site for asymmetrical
      methylation.
AB  - DNA methylation has been often proposed to operate as a genome defence system
      against parasitic mobile elements. To test this possibility, the methylation
      status of a class of plant mobile elements, the S1Bn SINEs, was analysed in
      detail using the bisulfite modification method. We observed that S1Bn SINE
      retroposons are methylated at symmetrical and asymmetrical positions. Methylated
      cytosines are not limited to transcriptionally important regions but are well
      distributed along the sequence. S1Bn SINE retroposons are two-fold more
      methylated than the average methylation level of the Brassica napus nuclear DNA.
      By in situ hybridization, we showed that this high level of methylation does not
      result from the association of S1Bn elements to genomic regions known to be
      highly methylated suggesting that S1Bn elements were specifically methylated. A
      detailed analysis of the methylation context showed that S1Bn cytosines in
      symmetrical CpG and CpNpG sites are methylated at a level of 87% and 44%
      respectively. We observed that 5.3% of S1Bn cytosines in non-symmetrical
      positions were also methylated. Of this asymmetrical methylation, 57% occurred at
      a precise motif (Cp(A/T)pA) that only represented 12% of the asymmetrical sites
      in S1Bn sequences suggesting that it represents a preferred asymmetrical
      methylation site. This motif is methylated in S1Bn elements at only half the
      level observed for the Cp(A/T)pG sites. We show that non-S1Bn CpTpA sites can
      also be methylated in DNA from B. napus and from other plant species.

PMID- 10080693
TI  - Characterization of the KNOX class homeobox genes Oskn2 and Oskn3 identified in a
      collection of cDNA libraries covering the early stages of rice embryogenesis.
AB  - For identification of genes involved in embryogenesis in the model cereal rice,
      we have constructed a collection of cDNA libraries of well-defined stages of
      embryo development before, during and after organ differentiation. Here, we focus
      on the possible role of KNOX (maize Knotted1-like) class homeobox genes in
      regulation of rice embryogenesis. Three types of KNOX clones were identified in
      libraries of early zygotic embryos. Two of these, Oskn2 and Oskn3, encode newly
      described KNOX genes, whereas the third (Oskn1) corresponds to the previously
      described OSH1 gene. In situ hybridizations showed that during the early stages
      of embryo development, all three KNOX genes are expressed in the region where the
      shoot apical meristem (SAM) is organizing, suggesting that these genes are
      involved in regulating SAM formation. Whereas OSH1 was previously proposed to
      function also in SAM maintenance, Oskn3 may be involved in patterning organ
      positions, as its expression was found to mark the boundaries of different
      embryonic organs following SAM formation. The expression pattern of Oskn2
      suggested an additional role in scutellum and epiblast development. Transgenic
      expression of Oskn2 and Oskn3 in tobacco further supported their involvement in
      cell fate determination, like previously reported for Knotted1 and OSH1 ectopic
      expression. Whereas Oskn3 transformants showed the most pronounced phenotypic
      effects during vegetative development, Oskn2 transformants showed relatively mild
      alterations in the vegetative phase but a more severely affected flower
      morphology. The observation that the KNOX genes produce similar though distinct
      phenotypic reponses in tobacco, indicates that their gene products act on
      overlapping but different sets of target genes, or that cell-type specific
      factors determine their precise action.

PMID- 10080694
TI  - Isolation and characterization of cDNA clones corresponding with mRNAs that
      accumulate during auxin-induced lateral root formation.
AB  - Lateral root formation in root cultures of Arabidopsis thaliana can be initiated
      by exogenous addition of auxin. In order to find cDNA clones of which the
      corresponding mRNAs accumulate during this process, a cDNA library was
      constructed from root cultures treated with the active auxin 1-naphthaleneacetic
      acid (1-NAA). Differential screening of this library with cDNA probes derived
      from mRNA populations isolated from root cultures treated with 1-NAA and the
      inactive analogue 2-naphthaleneacetic acid (2-NAA) led to the isolation of four
      cDNA clones, designated AIR1, AIR3, AIR9 and AIR12. Accumulation of the mRNAs
      starts between 4 and 8 h and continues till at least 24 h after addition of an
      active auxin. Sequence analysis revealed that AIR1 encodes a protein that is
      related to a large family of proteins that consist of a proline-rich or glycine
      rich N-terminus and a hydrophobic, possibly membrane spanning C-terminus. The
      putative function of these proteins is coupling of the cell wall to the plasma
      membrane. Surprisingly, AIR1 lacks the proline-rich or glycine-rich N-terminus
      which is thought to be important for interaction with the cell wall. AIR3 encodes
      a subtilisin-like serine protease which is believed to be active outside the
      plant cell. Although AIR9 and AIR12 do not show any significant homology to
      sequences in the database, they are also predicted to function outside the cell.
      Our screening thus indicates that a variety of genes encoding extracellular
      proteins are activated during auxin-induced lateral root formation.

PMID- 10080695
TI  - Light-regulated expression of the gsa gene encoding the chlorophyll biosynthetic
      enzyme glutamate 1-semialdehyde aminotransferase in carotenoid-deficient
      Chlamydomonas reinhardtii cells.
AB  - Expression of the Chlamydomonas reinhardtii gsa gene encoding the chlorophyll
      biosynthetic enzyme glutamate 1-semialdehyde aminotransferase was previously
      shown to be induced by blue light. Possible blue light photoreceptors include
      flavins and carotenoids. Light induction of gsa was investigated in carotenoid
      deficient mutant C. reinhardtii cells. Strain CC-2682 cells are sensitive to
      light, produce only small amounts of chlorophyll, and do not exhibit phototaxis.
      Solvent extracts show the absence of carotenoids and carotenoid precursors beyond
      phytoene in dark-grown mutant cells. Although apparently devoid of carotenoids,
      the cells did show light induction of gsa. The gsa transcript level was very low
      in dark-grown cells but increased significantly after 2 h of exposure to dim (1.5
      x 10(-5) mol m(-2) s(-1)) green (480-585 nm) light. This light regime was
      previously determined not to injure these photosensitive cells and to fully
      induce gsa in wild-type cells. Exposure to this light did not cause the mutant
      cells to produce measurable carotenoids or to become phototactic. Growth of the
      mutant cells in the presence of exogenous beta-carotene or all-trans retinol
      restored phototaxis but did not affect the degree of gsa induction by light. The
      induction of gsa by light in the absence of carotenoids, and the fact that
      incorporation of physiologically usable carotenoids (as indicated by the
      restoration of phototaxis) did not affect the degree of light induction, indicate
      that the photoreceptor for light induction of gsa in C. reinhardtii is not a
      carotenoid. The flavin antagonist diphenyleneiodonium blocked light induction of
      gsa in both wild-type and mutant cells under conditions where respiration was not
      inhibited. These results suggest that the photoreceptor or a signal transduction
      effector for light induction of the C. reinhardtii gsa gene is a flavoprotein.

PMID- 10080696
TI  - Structural conservation of the transposon Tam3 family in Antirrhinum majus and
      estimation of the number of copies able to transpose.
AB  - We have investigated the organization of the transposon Tam3 family in
      Antirrhinum majus. Genomic hybridization experiments and characterization of 40
      independent Tam3 clones isolated from an A. majus plant revealed that the Tam3
      family is quite conserved and the copy sizes are uniform. We did not find any
      copy with a deleted internal sequence, unlike what is usually observed in other
      transposons. This exceptionally conserved structure of the Tam3 family was
      confirmed by PCR and sequencing analyses. Sequencing analysis identified eight
      copies with sequences completely identical to that of the Tam3 transposase gene.
      These results suggested that a considerable number of autonomous Tam3 copies are
      present in the genome of A. majus. Among 24 copies which are surrounded by single
      copy regions of the genome, 14 copies are present as specific insertions in the
      line which we used, but absent in other lines. These copies are therefore
      predicted to be movable. If this ratio is the same for all Tam3 copies in a
      genome, then a maximum of 60% of the copies are estimated to be movable in the
      genome. The relatively high frequency of gene tagged by Tam3 might reflect the
      large number of movable copies in the genome.

PMID- 10080697
TI  - The role of protein surface charge in catalytic activity and chloroplast membrane
      association of the pea NADPH: protochlorophyllide oxidoreductase (POR) as
      revealed by alanine scanning mutagenesis.
AB  - NADPH:protochlorophyllide oxidoreductase (POR) catalyzes the light-dependent
      reduction of protochlorophyllide (pchlide) to chlorophyllide (chlide) in the
      biosynthesis of chlorophyll. POR is a peripheral membrane protein that
      accumulates to high levels in the prolamellar bodies of vascular plant etioplasts
      and is present at low levels in the thylakoid membranes of developing and mature
      plastids. Clustered charged-to-alanine scanning mutagenesis of the pea (Pisum
      sativum L.) POR was carried out and the resulting mutant enzymes analyzed for
      their ability to catalyze pchlide photoconversion in vivo and to associate
      properly with thylakoid membrane preparations in vitro. Of 37 mutant enzymes
      examined, 5 retained wild-type levels of activity, 14 were catalytically
      inactive, and the remaining 18 exhibited altered levels of function. Several of
      the mutant enzymes showed temperature-dependent enzymatic activity, being
      inactive at 32 degrees C, but partially active at 24 degrees C. Mutations in
      predicted alpha-helical regions of the protein showed the least effect on enzyme
      activity, whereas mutations in predicted beta-sheet regions of the protein showed
      a consistent adverse affect on enzyme function. In the absence of added NADPH,
      neither wild-type POR nor any of the mutant PORs resisted proteolysis by
      thermolysin following assembly onto the thylakoid membranes. In contrast, when
      NADPH was present in the assay mixture, 13 of the 37 mutant PORs examined were
      found to be resistant to thermolysin upon treatment, suggesting that the
      mutations did not affect their ability to be properly attached to the thylakoid
      membrane. In general, the replacement of charged amino acids by alanine in the
      most N- and C-terminal regions of the mature protein did not significantly affect
      POR assembly, whereas mutations within the central core of the protein (between
      residues 86 and 342) were incapable of proper attachment to the thylakoid.
      Failure to properly associate with the thylakoid membrane in a protease resistant
      manner was only weakly correlated to loss of catalytic function. These studies
      are a first step towards defining structural determinants crucial to POR function
      and intraorganellar localization.

PMID- 10080698
TI  - Expression of a proteasome alpha-type subunit gene during tobacco development and
      senescence.
AB  - Proteasomes degrade specific proteins that have been targeted for proteolysis by
      ubiquitination. In animals and yeast nuclear-localised proteasomes play a role in
      regulating the cell cycle, and other developmental processes, via control of the
      levels of regulatory nuclear proteins such as cyclins and transcription factors.
      A cDNA, NtPSA1, isolated from tobacco styles was found to have high similarity to
      human and yeast genes, PRCI_human and PRCI_yeast with 63.4% and 51.6% overall
      identity respectively. These genes are believed to encode non-catalytic alpha
      type subunits of 26S proteasomes and like NtPSA1 have putative nuclear
      localisation signals. NtPSA1 RNA was found to accumulate to varying levels in
      different parts of the plant and at different developmental stages. In
      particular, the level of NtPSA1 RNA was high in young dividing and expanding
      tissues, and declined during the senescence of both leaves and flowers. These
      results suggest that a role of proteasomes in plant nuclei may be to regulate
      developmental events by controlling the levels of regulatory proteins in
      proliferating and developing tissues, rather than to degrade and recycle proteins
      during senescence.

PMID- 10080699
TI  - Characterization of Urtica dioica agglutinin isolectins and the encoding gene
      family.
AB  - Urtica dioica agglutinin (UDA) has previously been found in roots and rhizomes of
      stinging nettles as a mixture of UDA-isolectins. Protein and cDNA sequencing have
      shown that mature UDA is composed of two hevein domains and is processed from a
      precursor protein. The precursor contains a signal peptide, two in-tandem hevein
      domains, a hinge region and a carboxyl-terminal chitinase domain. Genomic
      fragments encoding precursors for UDA-isolectins have been amplified by five
      independent polymerase chain reactions on genomic DNA from stinging nettle
      ecotype Weerselo. One amplified gene was completely sequenced. As compared to the
      published cDNA sequence, the genomic sequence contains, besides two basepair
      substitutions, two introns located at the same positions as in other plant
      chitinases. By partial sequence analysis of 40 amplified genes, 16 different
      genes were identified which encode seven putative UDA-isolectins. The deduced
      amino acid sequences share 78.9-98.9% identity. In extracts of roots and rhizomes
      of stinging nettle ecotype Weerselo six out of these seven isolectins were
      detected by mass spectrometry. One of them is an acidic form, which has not been
      identified before. Our results demonstrate that UDA is encoded by a large gene
      family.

PMID- 10080700
TI  - Tissue-specific expression of two genes for sucrose synthase in carrot (Daucus
      carota L.).
AB  - Sucrose synthase, which cleaves sucrose in the presence of uridine diphosphate
      (UDP) into UDP-glucose and fructose, is thought to be a key determinant of sink
      strength of heterotrophic plant organs. To determine the roles of the enzyme in
      carrot, we characterized carrot sucrose synthase at the molecular level. Two
      genes (Susy*Dc1 and Susy*Dc2) were isolated. The deduced amino acid sequences are
      87% identical. However, the sequences upstream of the translation initiation
      codons are markedly different, as are the expression patterns of the two genes.
      Susy*Dc2 was exclusively expressed in flowers. Transcripts for Susy*Dc1 were
      found in stems, in roots at different developmental stages, and in flower buds,
      flowers and maturing seeds, with the highest levels in strong utilization sinks
      for sucrose such as growing stems and tap root tips. Expression of Susy*Dc1 was
      regulated by anaerobiosis but not by sugars or acetate. The carrot sucrose
      synthase protein is partly membrane-associated and this insoluble form may be
      directly involved in cellulose biosynthesis. Tap roots of the carrot cultivar
      used accumulated starch in the vicinity of the vascular bundles, which correlated
      with high sucrose synthase transcript levels. This finding suggests that soluble
      sucrose synthase in tap roots channels sucrose towards starch biosynthesis.
      Starch accumulation appears to be transient and may be involved in sucrose
      partitioning to developing tap roots.

PMID- 10080701
TI  - Regulation of biosynthesis and cellular localization of Sp32 annexins in tobacco
      BY2 cells.
AB  - Annexins interact in a calcium-dependent manner with membrane phospholipids.
      Although their exact function is not known, annexins have been proposed to be
      involved in a variety of cellular processes. To determine whether plant annexins
      are implicated in cell division, we have isolated cDNAs encoding annexin from
      TBY2 cells. Based on sequence analysis, these cDNAs fall into two families,
      differing mainly by deletions or insertions in their 5'- and 3'-untranslated
      regions. The two annexins Ntp32.1 and Ntp32.2 encoded by these cDNAs are
      homologous to p32 from bell pepper (Cap32.1): we propose that these Solanaceae
      annexins constitute a distinct type which we call Sp32 annexins. There are two
      genes (Ntan.1 and Ntan.2) derived from the separate progenitor species of
      Nicotiana tabacum and analysis of Southern blots is consistent with the presence
      of these two genes. We show that Sp32 transcript amounts are developmentally
      modulated in tobacco plants: RNA levels are highest in growing and dividing
      tissues. Sp32 annexin gene expression is also regulated in TBY2 cultured cells:
      transcripts and proteins are detected only in exponentially growing cells. In
      synchronized TBY2 cells, Sp32 annexin transcripts are expressed at the G2/M
      transition, in the M phase and at the G1/S transition. These results are the
      first evidence that the expression of plant annexins is modulated during the cell
      cycle. The Sp32 annexin proteins accumulate during the cell cycle and peak at the
      end of mitosis. Immunolocalization shows that the majority of Sp32 annexins is
      present in intercellular junctions, forming a ring structure under the plasma
      membrane. Since annexins are known to bind secretory vesicles during exocytosis,
      their localization at cell junctions suggests that annexins could be involved in
      cell wall maturation.

PMID- 10080702
TI  - Ivr2, a candidate gene for a QTL of vacuolar invertase activity in maize leaves.
      Gene-specific expression under water stress.
AB  - Water shortage produced an early and large stimulation of acid-soluble invertase
      activity in adult maize leaves whereas cell wall invertase activity remained
      constant. This response was closely related to the mRNA level for only one of the
      invertase gene (Ivr2), encoding a vacuolar isoform. In parallel, four
      quantitative trait loci (QTLs) were detected for invertase activity under control
      and nine under stressful conditions. One QTL in control and one in stressed
      plants was located near to the Ivr2 gene on chromosome 5. Other QTLs for
      invertase activity were found close to carbohydrate QTLs; some of them formed
      'stress clusters'.

PMID- 10080703
TI  - Random mutagenesis in the large extrinsic loop E and transmembrane alpha-helix VI
      of the CP 47 protein of Photosystem II.
AB  - The intrinsic chlorophyll-protein CP 47 is a component of Photosystem II which
      functions in both light-harvesting and oxygen evolution. Using the Escherichia
      coli mutator strain XL-1 Red, we introduced mutations at 14 sites in the large
      extrinsic loop E of CP 47 and its adjacent transmembrane alpha-helix VI. Four
      mutant cell lines were recovered in which the histidyl residues 455H, 466H and
      469H were altered. The cell lines H455T, H455Y, H469Y, and the double mutant
      F432L,H466R exhibited phenotypes that supported the identification of the
      histidyl residues 455H, 466H and 469H as chlorophyll ligands. Four additional
      mutant cell lines were recovered which contained mutations at positions 448R in
      the large extrinsic loop of CP 47. These mutants, R448K, R448Q, R448S, and R448W,
      exhibited variable phenotypes ranging from moderate alteration of
      photoautotrophic growth and oxygen evolution rates to a complete inhibition of
      these parameters. Those mutants exhibiting photoautotrophic growth and oxygen
      evolution capability under standard conditions were unable to grow
      photoautotrophically or evolve oxygen when grown at low chloride concentrations.
      Finally, a mutant cell line exhibiting a substitution at position 342G was
      recovered. The mutant G342D exhibited moderate alterations of photoautotrophic
      growth and oxygen evolution. In addition to these alterations, mutants were
      recovered in which deletions and insertions (leading to frame shifts) and stop
      codons were introduced. These mutants uniformly lacked the ability to either grow
      photoautotrophically or evolve oxygen.

PMID- 10080704
TI  - Cloning and characterization of the nuclear AC115 gene of Chlamydomonas
      reinhardtii.
AB  - The nuclear ac115 mutant of Chlamydomonas reinhardtii is specifically blocked in
      the synthesis of the chloroplast encoded D2 protein of the photosystem II
      reaction center at a point after translation initiation. Here, we report the
      identification of the AC115 gene through complementation rescue of the ac115
      mutant strain, using an indexed cosmid library of Chlamydomonas genomic DNA.
      AC115 is a small, novel, intronless nuclear gene which encodes a protein of 113
      amino acids. The amino terminal end of the Ac115 protein is rich in basic amino
      acids and has features which resemble a chloroplast transit sequence. A
      hydrophobic stretch of amino acids at the protein's carboxyl terminus is
      sufficiently large to be a membrane spanning or a protein/protein interaction
      domain. Various models are discussed to account for the mechanism by which Ac115p
      works in D2 synthesis. The ac115 mutant allele was sequenced and determined to be
      an A-to-T transversion at the first position of the fourth codon of the coding
      sequence. This mutation changes an AAG codon to a TAG nonsense codon and results
      in a null phenotype.

PMID- 10080705
TI  - Characterization of the regulatory elements of the maize P-rr gene by transient
      expression assays.
AB  - The maize P-rr gene conditions floral-specific flavonoid pigmentation, especially
      in the kernel pericarp and cob. We analyzed the P-rr promoter by transient
      expression assays, in which segments of the P-rr promoter were fused to the GUS
      reporter gene and introduced into maize cells by particle bombardment. A basal P
      rr promoter fragment (-235 to +326) gave low, but significant, levels of GUS
      reporter gene expression. Interestingly, two widely spaced segments containing
      enhancer-like activity were found. When tested individually, both the proximal (
      1252 to -236) and distal (-6110 to -4842) segments boosted expression of the
      basal P-rr promoter::GUS construct about five-fold. A 1.6 kb segment of the P-rr
      promoter (-1252 to +326) containing the proximal enhancer and the 5'-untranslated
      leader driving the GUS reporter gene showed preferential expression in BMS and
      embryogenic suspension cell cultures vs. endosperm-derived suspension cell
      cultures. These results demonstrate the application of transient assay techniques
      for the identification of regulatory elements responsible for floral-specific
      regulation of the complex P-rr gene promoter in maize.

PMID- 10080706
TI  - Coordinate and non-coordinate expression of the stress 70 family and other
      molecular chaperones at high and low temperature in spinach and tomato.
AB  - Stress 70 molecular chaperones are found in all the major subcellular
      compartments of plant cells, and they are encoded by a multigene family. Twelve
      members of this family have been identified in spinach. The expression of the
      stress 70 molecular chaperones in response to heat shock is well-known and it
      appears that low temperature exposure can also stimulate their expression.
      However, it has been difficult to determine which member(s) of the family are
      specifically responsive to low temperature. This study was initiated to determine
      the levels of expression of the stress 70 family members and other selected
      chaperones in response to high and low temperature exposure. During heat shock of
      spinach, of the 10 stress 70 family members that were examined, all 10 showed
      increased RNA levels after one hour, and all showed down-regulation at longer
      durations of high temperature exposure. However, the response to low temperature
      was quite variable and complex. Some members were induced, some were transiently
      up-regulated, while others showed sustained up-regulation at a low non-freezing
      temperature. In comparison, the entirety of the molecular chaperone expression
      response of cold-sensitive tomato at the same low non-freezing temperature was
      even more dramatic with 11 of 15 molecular chaperones tested exhibiting elevated
      expression. The increased chaperone expression is consistent with the hypothesis
      that the biogenesis or stability of some proteins is compromised at low non
      freezing temperatures. In contrast, mild freezing sufficient to cause injury of
      spinach did not materially activate chaperone expression.

PMID- 10080707
TI  - Isolation and characterization of an anther-specific gene, RA8, from rice (Oryza
      sativa L.).
AB  - An anther-specific cDNA clone of rice, RA8, was isolated from an anther cDNA
      library by differential screening. RNA blot analysis indicated that the RA8
      transcript is present specifically in anthers and the transcript level increased
      as flowers matured, reaching the highest level in mature flowers. The RA8 clone
      contains an open reading frame of 264 amino acid residues with a hydrophobic N
      terminal region. The deduced amino acid sequences did not show significant
      homology to any known sequences. Genomic DNA blot analysis showed that RA8 is a
      single-copy gene. A genomic clone corresponding to the RA8 cDNA was isolated and
      its promoter region was fused to the beta-glucuronidase (GUS) gene. Transgenic
      rice plants exhibited anther-specific expression of the GUS reporter gene.
      Histochemical GUS analysis showed that the RA8 promoter was active in the
      tapetum, endothecium, and connective tissues of anthers. Experiments showed that
      expression of the gene starts when microspores are released from tetrads, and it
      reaches to the maximum level at the late vacuolated-pollen stage. The RA8
      promoter may be useful for controlling gene expression in anthers of cereal
      plants and for generating male-sterile plants.

PMID- 10080708
TI  - Molecular characterization of four beta-tubulin genes from dinitroaniline
      susceptible and resistant biotypes of Eleusine indica.
AB  - Dinitroaniline herbicides are antimicrotubule drugs that bind to tubulins and
      inhibit polymerization. As a result of repeated application of dinitroaniline
      herbicides, resistant biotypes of goosegrass (Eleusine indica) developed in
      previously susceptible wild-type populations. We have previously reported that
      alpha-tubulin missense mutations correlate with dinitroaniline response
      phenotypes (Drp) (Plant Cell 10: 297-308, 1998). In order to ascertain
      associations of other tubulins with dinitroaniline resistance, four beta-tubulin
      cDNA classes (designated TUB1, TUB2, TUB3, and TUB4) were isolated from
      dinitroaniline-susceptible and -resistant biotypes. Sequence analysis of the four
      beta-tubulin cDNA classes identified no missense mutations. Identified nucleotide
      substitutions did not result in amino acid replacements. These results suggest
      that the molecular basis of dinitroaniline resistance in goosegrass differs from
      those of colchicine/dinitroaniline cross-resistant Chlamydomonas reinhardtii and
      benzimidazole-resistant fungi and yeast. Expression of the four beta-tubulins was
      highest in inflorescences. This is in contrast to alpha-tubulin TUA1 that is
      expressed predominantly in roots. Collectively, these results imply that beta
      tubulin genes are not associated with dinitroaniline resistance in goosegrass.
      Phylogenetic analysis of the four beta-tubulins, together with three alpha
      tubulins, suggests that the resistant biotype developed independently in multiple
      locations rather than spreading from one location.

PMID- 10080709
TI  - Molecular cloning and characterization of Vigna mungo processing enzyme 1 (VmPE
      1), an asparaginyl endopeptidase possibly involved in post-translational
      processing of a vacuolar cysteine endopeptidase (SH-EP).
AB  - Asparaginyl endopeptidase is a cysteine endopeptidase that has strict substrate
      specificity toward the carboxy side of asparagine residues. Vigna mungo
      processing enzyme 1, termed VmPE-1, occurs in the cotyledons of germinated seeds
      of V. mungo, and is possibly involved in the post-translational processing of a
      vacuolar cysteine endopeptidase, designated SH-EP, which degrades seed storage
      protein. VmPE-1 also showed a substrate specificity to asparagine residues, and
      its enzymatic activity was inhibited by NEM but not E-64. In addition, purified
      VmPE-1 had a potential to process the recombinant SH-EP precursor to its
      intermediate in vitro. cDNA clones for VmPE-1 and its homologue, named VmPE-1A,
      were identified and sequenced, and their expressions in the cotyledons of V.
      mungo seedlings and other organs were investigated. VmPE-1 mRNA and SH-EP mRNA
      were expressed in germinated seeds at the same stage of germination although the
      enzymatic activity of VmPE-1 rose prior to that of SH-EP. The level of VmPE-1A
      mRNA continued increasing as germination proceeded. In roots, stems and leaves of
      fully grown plants, and in hypocotyls, VmPE-1 and VmPE-1A were little expressed.
      We discuss possible functions of VmPE-1 and VmPE-1A in the cotyledons of
      germinated seeds.

PMID- 10080710
TI  - Characterization of DRGs, developmentally regulated GTP-binding proteins, from
      pea and Arabidopsis.
AB  - Developmentally regulated GTP-binding proteins (DRGs) from animals and fungi are
      highly conserved but have no known function. Here we characterize DRGs from pea
      (PsDRG) and Arabidopsis (AtDRG). Amino acid sequences of AtDRG and PsDRG were 90%
      identical to each other and about 65% identical to human DRG. Genomic Southern
      blotting indicated that AtDRG and PsDRG probably are single-copy genes. PsDRG
      mRNA accumulated preferentially in growing organs (root apices, growing axillary
      buds and elongating stems) compared with their non-growing counterparts. At DRG
      mRNA was relatively abundant in Arabidopsis leaves, stems and siliques, less
      abundant in flowers and flower buds, and barely detectable in roots. Histone
      mRNAs are known to accumulate predominantly during S phase of the cell cycle and
      are markers for proliferating cells. The patterns of histone H2A mRNA
      accumulation in pea and Arabidopsis organs were very similar to those of DRG
      mRNAs. An antiserum raised against a PsDRG N-terminal fusion protein recognized
      43 and 45 kDa proteins. PsDRG proteins were more abundant in growing pea roots
      and stems than in non-growing organs, but they were equally abundant in growing
      and dormant axillary buds. After differential centrifugation, PsDRG proteins were
      found primarily in the microsomal (150,000 x g pellet) and soluble (150,000 x g
      supernatant) cell fractions.

PMID- 10080711
TI  - Positive-negative selection and T-DNA stability in Arabidopsis transformation.
AB  - We have analysed the application of positive-negative selection for the selection
      of homologous recombination interactions between the chromosome and a T-DNA
      molecule after transformation of plant cells. Two different genomic loci in a
      cell suspension of Arabidopsis thaliana were chosen to study gene targeting
      events. One was the chalcone synthase (CHS) gene present as a single copy and the
      second an hemizygous chromosomally inserted T-DNA containing the hpt gene,
      conferring resistance to hygromycin, flanked by CHS sequences. The target lines
      were transformed with replacement-type T-DNA vectors which contained a positive
      selectable marker flanked by the regions of the CHS gene and a negative
      selectable marker to counter-select random insertions. As negative marker we used
      the Escherichia coli codA gene encoding cytosine deaminase, conferring upon the
      cells sensitivity to 5-flourocytosine (5-FC). Doubly selected transformants
      represent 1-4% of the primary transformed cells. Targeting events were not found
      at the chalcone synthase locus nor at the artificial hpt locus in a total of 4379
      doubly selected calli, corresponding to at least 109,475 individual primary
      transformants. We show by PCR and Southern analysis that the 5-FC resistance in
      the majority of these cells is associated with substantial deletions of the T-DNA
      molecule from the right-border end.

PMID- 10080712
TI  - Identification of a DNA-binding factor that recognizes an alpha-coixin promoter
      and interacts with a Coix Opaque-2 like protein.
AB  - Transient expression and electrophoretic mobility shift assay were used to
      investigate the cis elements and the DNA-binding proteins involved in the
      regulation of expression of a 22 kDa zein-like alpha-coixin gene. A set of
      unidirectional deletions was generated in a 962 bp fragment of the alpha-coixin
      promoter that had been previously fused to the reporter gene GUS. The constructs
      were assayed by transient expression in immature maize endosperm. There was no
      significant decrease in GUS activity as deletions progressed from -1084 to -238.
      However, deletion from -238 to -158, which partially deleted the O2c box,
      resulted in a dramatic decrease in GUS activity emphasizing the importance of the
      O2 box in the quantitative expression of the gene. The -238 promoter fragment
      interacted with Coix endosperm nuclear proteins to form 5 DNA-protein complexes,
      C1-C5, as detected by EMSA. The same retarded complexes were observed when the 
      158 promoter fragment was used in the binding reactions. Reactions with nuclear
      extracts isolated from Coix endosperms harvested from 6 to 35 days after
      pollination revealed that the 5 DNA-protein complexes that interact with the
      alpha-coixin promoter are differentially assembled during seed development.
      Deletion analysis carried out on the -238/ATG promoter fragment showed that a 35
      bp region from -86 to -51 is essential for the formation of the complexes
      observed. When nuclear extracts were incubated with an antiserum raised against
      the maize Opaque-2 protein, the formation of 4 complexes, C1, C3, C4 and C5, was
      prevented indicating that an Opaque-2 like protein participates in the formation
      of those complexes. Complex C2 was not affected by the addition of the O2
      antibody, suggesting the existence of a novel nuclear factor, CBF1, that binds to
      the promoter and makes protein-protein associations with other proteins present
      in Coix endosperm nuclei.

PMID- 10080713
TI  - Molecular characterization of catalytic-subunit cDNA sequences encoding protein
      phosphatases 1 and 2A and study of their roles in the gibberellin-dependent Osamy
      c expression in rice.
AB  - To understand the molecular mechanism of gibberellin-dependent gene regulation,
      the effect of three phosphatase inhibitors on the germination of rice seeds and
      the expression of a target gene, the alpha-amylase gene, Osamy-c, were measured.
      We found that okadaic acid, microcystin-LR, and calyculin A, which are known to
      specifically inhibit Ser/Thr phosphatases 1 and 2A, strongly inhibit the
      expression of the Osamy-c and may be involved in the germination of rice seeds.
      The protein phosphatase enzyme activity assays showed that there is no obvious
      effect of GA3 on total PP1/PP2A activities. To further understand the possible
      role of protein phosphatases 1 and 2A in the GA-dependent expression of Osamy-c,
      we isolated cDNA clones encoding protein phosphatase 1 and protein phosphatase 2A
      from a rice aleurone cDNA library. These were designated OsPP1c and OsPP2Ac,
      respectively. Comparison of the deduced amino acid sequences of OsPP1c and
      OsPP2Ac with the catalytic subunits of PP1 or PP2A of rabbit skeletal muscle,
      Arabidopsis thaliana, maize and Brassica napus showed that the catalytic subunit
      sequences of PP1 or PP2A among these organisms are highly conserved (73% to 90%
      similarity). Genomic Southern blot analysis indicated that there are only one or
      two copies of OsPP1c genes and more than two copies of OsPP2Ac genes in the rice
      genome. Northern blot analysis showed that OsPP1c and OsPP2Ac genes are expressed
      in several organs of rice, including seed, shoot and root. We also showed by
      using 3' gene-specific probes of OsPP1c and OsPP2Ac cDNA, that the expression of
      neither gene is regulated by GA. Taken together, our results suggest that protein
      phosphatases PP1 or PP2A are involved in the GA-dependent expression of the rice
      Osamy-c gene, though the PP1 or/and PP2A enzymatic activities as well as mRNA
      levels do not increase upon GA3 treatment.

PMID- 10080714
TI  - The wheat LEA protein Em functions as an osmoprotective molecule in Saccharomyces
      cerevisiae.
AB  - The biased amino acid composition and aperiodic (random coil) configuration of
      Group 1 late embryogenesis-abundant (LEA) proteins imply that these proteins are
      capable of binding large amounts of water. While Group 1 LEAs have been predicted
      to contribute to osmotic stress protection in both embryonic and vegetative
      tissues, biochemical support has been lacking. We have used Saccharomyces
      cerevisiae as a model system to test the putative osmoprotective function of a
      wheat Group 1 LEA protein, Em. We demonstrate that expression of Em protein in
      yeast cells is not deleterious to growth in media of normal osmolarity and
      attenuates the growth inhibition normally observed in media of high osmolarity.
      Enhanced growth is observed in the presence of a variety of osmotically active
      compounds indicating that Em protein is capable of mitigating the detrimental
      effect of low water potential in a relatively non-specific manner. These results
      are the first biochemical demonstration of an osmoprotective function for a Group
      1 LEA and suggest that the yeast expression system will be useful in dissecting
      the mechanism of protection through structure-function studies.

PMID- 10080715
TI  - Elicitor-responsive promoter regions in the tryptophan decarboxylase gene from
      Catharanthus roseus.
AB  - The tryptophan decarboxylase (Tdc) gene from Catharanthus roseus (Madagascar
      periwinkle) encodes a key enzyme in biosynthesis of terpenoid indole alkaloids.
      The expression of the Tdc gene is transcriptionally induced by fungal elicitors.
      Tdc upstream sequences from -1818 to +198 relative to the transcriptional start
      site were functionally analysed to identify cis-acting elements that determine
      basal expression or respond to elicitor. In a loss-of-function analysis promoter
      derivatives with 5' or internal deletions fused to the gusA reporter gene were
      analysed in transgenic tobacco plants. Whereas promoter activity dropped
      considerably following deletion down to -160, this short promoter derivative was
      still elicitor-responsive. Subsequently, the -160 to -37 region was further
      studied by gain-of-function experiments, in which subfragments were tested as
      tetramers cloned on two different truncated promoters. Combination of the data
      resulted in the identification of three functional regions in the -160 promoter.
      The region between -160 to -99 was shown to act as the main transcriptional
      enhancer. Two separable elicitor-responsive elements were found to reside between
      -99 and -87 and between -87 and -37. These two elements are not redundant in the
      Tdc promoter, since their combination gave a distinct elicitor response.

PMID- 10080716
TI  - Characterization of three novel members of the Arabidopsis SHAGGY-related protein
      kinase (ASK) multigene family.
AB  - In this paper we report the characterization of three novel members of the
      Arabidopsis shaggy-related protein kinase (ASK) multigene family, named ASKdzeta
      (ASKzeta), ASKetha (ASKeta) and ASKiota (ASKiota). The proteins encoded by the
      ASK genes share a highly conserved catalytic protein kinase domain and show about
      70% identity to SHAGGY (SGG) and glycogen synthase kinase-3 (GSK-3) from
      Drosophila and rat respectively. SGG is an ubiquitous intracellular component of
      the wingless signalling pathway that establishes cell fate and/or pattern
      formation in Drosophila. At least ten different ASK genes are expected to be
      present per haploid genome of A. thaliana. Different amino- and carboxy-terminal
      extensions distinguish different ASK family members. Five ASK gene sequences were
      analysed and shown to be present as single-copy genes in the Arabidopsis genome.
      A comparison based on the highly conserved catalytic domain sequences of all
      known sequences of the GSK-3 subfamily of protein kinases demonstrated a clear
      distinction between the plant and the animal kinases. Furthermore, we established
      the presence of at least three distinct groups of plant homologues of SGG/GSK-3.
      These different groups probably reflect biochemical and/or biological properties
      of these kinases. The differential expression patterns of five ASK genes were
      accessed by northern and in situ hybridization experiments using gene-specific
      probes. While ASKzeta is expressed in the whole embryo during its development,
      ASKeta expression is limited to the suspensor cells. No signal was detected for
      ASKalpha, ASKgamma and ASKiota in developing embryos.

PMID- 10080717
TI  - Molecular characterization of a gene for alanine aminotransferase from rice
      (Oryza sativa).
AB  - A cDNA clone encoding alanine aminotransferase (AlaAT) has isolated from randomly
      sequenced clones derived from a cDNA library of maturing rice seeds by comparison
      to previously identified genes. The deduced amino acid sequence was 88% and 91%
      homologous to those of the enzymes from barley and broomcorn millet (Panicum
      miliaceum), respectively. Using this cDNA as a probe, we isolated and sequenced
      the corresponding genomic clone. Comparison of the sequences of the cDNA and the
      genomic gene revealed that the coding region of the gene was interrupted by 14
      introns 66 to 1547 bp long. Northern and western blotting analyses showed that
      the gene was expressed at high levels in developing seeds. When the 5'-flanking
      region between -930 and +85 from the site of initiation of transcription was
      fused to a reporter gene for beta-glucuronidase (GUS) and then introduced into
      the rice genome, histochemical staining revealed strong GUS activity in the inner
      endosperm tissue of developing seeds and weak activity in root tips. Similar
      tissue-specific expression was also detected by in situ hybridization. These
      results suggest that AlaAT is involved in nitrogen metabolism during the
      maturation of rice seed.

PMID- 10080718
TI  - Differential expression of expansin gene family members during growth and
      ripening of tomato fruit.
AB  - cDNA clones encoding homologues of expansins, a class of cell wall proteins
      involved in cell wall modification, were isolated from various stages of growing
      and ripening fruit of tomato (Lycopersicon esculentum). cDNAs derived from five
      unique expansin genes were obtained, termed tomato Exp3 to Exp7, in addition to
      the previously described ripening-specific tomato Exp1 (Rose et al. (1997) Proc
      Natl Acad Sci USA 94: 5955-5960). Deduced amino acid sequences of tomato Exp1,
      Exp4 and Exp6 were highly related, whereas Exp3, Exp5 and Exp7 were more
      divergent. Each of the five expansin genes showed a different and characteristic
      pattern of mRNA expression. mRNA of Exp3 was present throughout fruit growth and
      ripening, with highest accumulation in green expanding and maturing fruit, and
      lower, declining levels during ripening. Exp4 mRNA was present only in green
      expanding fruit, whereas Exp5 mRNA was present in expanding fruit but had highest
      levels in full-size maturing green fruit and declined during the early stages of
      ripening. mRNAs from each of these genes were also detected in leaves, stems and
      flowers but not in roots. Exp6 and Exp7 mRNAs were present at much lower levels
      than mRNAs of the other expansin genes, and were detected only in expanding or
      mature green fruit. The results indicate the presence of a large and complex
      expansin gene family in tomato, and suggest that while the expression of several
      expansin genes may contribute to green fruit development, only Exp1 mRNA is
      present at high levels during fruit ripening.

PMID- 10080719
TI  - Genetic and physical characterization of a region of Arabidopsis chromosome 1
      containing the CLAVATA1 gene.
AB  - With the advance of Arabidopsis as a model system for understanding plant
      genetics, development and biochemistry, a detailed description of the genome is
      necessary. As such, focused projects are underway to map and sequence the
      Arabidopsis nuclear genome. We have characterized a region of chromosome 1,
      surrounding the CLAVATA1 (CLV1) locus. Three (RFLP) clones were mapped relative
      to clv1-1, and were used to construct an ca. 700 kb yeast artificial chromosome
      (YAC) contig. Three cosmids spanning the CLV1 locus were analyzed and ca. 24 kb
      of genomic DNA was sequenced, including a continuous stretch of 18 kb. In
      addition to generating clones in this region of chromosome 1, we have analyzed
      the size, spacing and organization of several contiguous genes.

PMID- 10080720
TI  - The soybean ENOD40(2) promoter is active in Arabidopsis thaliana and is
      temporally and spatially regulated.
AB  - The ENOD40 gene is induced early during Rhizobium-legume symbiosis and has
      probably a primary role in the nodule organogenesis. In this paper we show that
      the 1.7 kb 5'-flanking region of the GmENOD40(2) is able to drive the expression
      of a gusA-int marker in transgenic Arabidopsis thaliana. The promoter activity is
      developmentally regulated and the major activity is detected in the root and in
      the stigma.

PMID- 10080721
TI  - Identification and expression of the kosena radish (Raphanus sativus cv. Kosena)
      homologue of the ogura radish CMS-associated gene, orf138.
AB  - A CMS-associated gene, orf125, present in the Japanese radish cultivar Kosena,
      has a sequence homologous to that of the ogura CMS-associated gene, orf138,
      except for two amino acid substitutions and a 39 bp deletion in the orf138 coding
      region. In Kosena radish, orf125 is linked with orfB, whereas the orf125 locus
      differs in a Brassica napus CMS cybrid derived from protoplast fusion between
      Kosena radish and B. napus. A novel mtDNA sequence is present in the 3'-flanking
      region of orf125 in the B. napus kosena CMS cybrid. The orf125 is expressed both
      in the radish and the B. napus kosena CMS cybrid. Its accumulation is strongly
      associated with the CMS phenotype in B. napus. Fertility restoration was
      accompanied by a decrease in the amount of ORF125 in B. napus.

PMID- 10080722
TI  - Endosonography, the last frontier of ultrasound?

PMID- 10080723
TI  - Endosonography in gastrointestinal diseases.

PMID- 10080724
TI  - MR imaging with gadolinium in patients with and without post-lumbar puncture
      headache.
AB  - PURPOSE: To study frequency and extent of meningeal enhancement in patients with
      and without post-lumbar puncture headache (PLPH) with cerebral MR with Gd-DTPA.
      MATERIAL AND METHODS: Ten consecutive patients with PLPH and 9 consecutive
      patients without PLPH were included in the study. Nine of the PLPH patients were
      reinvestigated when the PLPH was over and all non-PLPH patients during the week
      after the lumbar puncture. RESULTS: Eight of the 9 patients with PLPH showed more
      enhancement of meningeal structures during PLPH than when PLPH had disappeared.
      The differences were slight in 5, more marked in 2, and pronounced in 1 patient.
      The 9th patient showed no change at all. In the 9 patients without PLPH, there
      was mainly slight enhancement before lumbar puncture and no change in enhancement
      after lumbar puncture as compared with before. CONCLUSION: PLPH is related to
      increased Gd-DTPA enhancement of the meninges, although the increase in
      enhancement during PLPH is minor in most cases. Pronounced enhancement of the
      meninges after lumbar puncture may predict long duration of the PLPH.

PMID- 10080725
TI  - High intensity signal of the posterior pituitary. A study with horizontal
      direction of frequency-encoding and fat suppression MR techniques.
AB  - PURPOSE: To evaluate the consistency of fat in the high intensity signals of the
      normal neurohypophysis and to differentiate the high signal of posterior
      pituitary from that of dorsum sella. Sagittal SE T1-weighted images with
      frequency encoding in the horizontal direction were used in order to
      differentiate the high signal of posterior pituitary and dorsum sella by the
      vertically-oriented chemical shift artifact. MATERIAL AND METHODS: The sellae of
      46 normal volunteers were imaged with a commercially available fat suppression
      technique and SE sequences with frequency encoding in vertical (25 cases) and
      horizontal (21 cases) axes. RESULTS: The high signal intensity was absent in 9%
      of the normal volunteers with no predilection to any specific age group. None of
      the cases with posterior pituitary high intensity signals showed suppression of
      the signal with fat suppression technique. A fat suppression technique was
      helpful in documenting the hyperintensity in 7% of normal volunteers. Nineteen of
      the 21 (90%) cases with high signal intensity were detected by routine SE T1
      weighted images, whereas 18 of the 19 (95%) cases were detected by imaging with
      frequency encoding in the horizontal direction. CONCLUSION: The high signal does
      not indicate the presence of fat. Fat suppression technique and a horizontal
      direction of frequency encoding help in differentiating the high signal of the
      neurohypophysis from that of dorsum sella.

PMID- 10080726
TI  - Kinematic MR imaging in surgical management of cervical disc disease, spondylosis
      and spondylotic myelopathy.
AB  - PURPOSE: To estimate the clinical value and influence of kinematic MR imaging in
      patients with degenerative diseases of the cervical spine. MATERIAL AND METHODS:
      Eighty-one patients were examined with a 1.5 T whole body magnet using a
      positioning device. Cervical disc disease was classified according to clinical
      and radiographic findings into 4 stages: stage I=cervical disc disease (n=13);
      stage II=spondylosis (n=42); stage III=spondylosis with restricted motion (n=11);
      and stage IV=cervical spondylotic myelopathy (n=15). Findings on kinematic MR
      images were compared to those on flexion and extension radiographs, myelography,
      CT-myelography and static MR imaging. Furthermore, the influence of kinematic MR
      imaging on surgical management and intra-operative patient positioning was
      determined. RESULTS: Additional information obtained by kinematic MR imaging
      changed the therapeutic management in 7 of 11 (64%) patients with stage III
      disease, and in 13 of 15 (87%) patients with stage IV disease. Instead of an
      anterior approach, a posterior surgical approach was chosen in 3 of 11 patients
      (27%) with stage III disease and in 6 of 15 patients (40%) with stage IV disease.
      Hyperextension of the neck was avoided intra-operatively in 4 patients (27%) with
      cervical spondylotic myelopathy, and in 1 patient with stage II (2%) and in 1
      patient with stage III (9%) disease. Kinematic MR imaging provided additional
      information in all patients with stages III and IV disease except in 1 patient
      with stage III disease, when compared to flexion and extension radiographs,
      myelography, CT-myelography and static MR examination. CONCLUSION: Kinematic MR
      imaging adds additional information when compared to conventional imaging methods
      in patients with advanced stages of degenerative disease of the cervical spine.

PMID- 10080727
TI  - CT and MR imaging of the paranasal sinuses in cystic fibrosis. Correlation with
      microbiological and histopathological results.
AB  - PURPOSE: To compare CT and MR findings of the paranasal sinuses in patients with
      cystic fibrosis (CF) with microbiology and histopathology. Further, to compare
      microbiology from the maxillary sinuses, nasopharynx and sputum. MATERIAL AND
      METHODS: CT and MR imaging of the paranasal sinuses were performed in 10 CF
      patients. Endoscopy and maxillary sinus aspirates were obtained (guided by the MR
      findings) and analyzed microbiologically and histologically. Samples from the
      nasopharynx and sputum were analyzed microbiologically. RESULTS: CT and MR were
      equal in displaying the extent of soft tissue masses, which at CT were
      homogeneous, while MR showed heterogeneous signals. MR images also demonstrated
      circumscribed areas with signal void at the STIR sequence with corresponding high
      to intermediate signal at the T1-weighted sequence. P. aeruginosa was frequently
      cultured from these areas which we named the "black hole sign". Maxillary sinus
      cultures revealed the same bacteria as nasopharynx and sputum cultures combined.
      CONCLUSION: MR images were superior to CT in differentiating soft tissue masses
      in the paranasal sinuses in CF patients. Bacteria with potential for specialized
      iron uptake mechanisms were present in areas with signal void at the STIR
      sequence. Our hypothesis is that the MR "black hole sign" can be explained by
      paramagnetic properties related to bacterial agents.

PMID- 10080728
TI  - Diagnostic value of ultrasonography in patients with palpable mammographically
      noncalcified breast tumors.
AB  - PURPOSE: To analyze the diagnostic accuracy of mammography, ultrasonography (US),
      and both methods combined in evaluation of palpable noncalcified breast tumors.
      MATERIAL AND METHODS: Mammograms and sonograms of 200 patients with palpable
      noncalcified breast masses were retrospectively analyzed independently by four
      experienced radiologists in 3 sessions: Mammography or US interpretations in the
      first two and combined reading in the last session. Nonneoplastic abnormalities
      and mammographically obvious cancers were excluded. Receiver operating
      characteristic (ROC) analyses were performed for 115 (60 benign and 55 malignant)
      tumors and subgroups according to tissue density and tumor size. A single ROC
      curve for each diagnostic test was obtained by pooling the individual ratings.
      The area under the ROC curve was used as a measure of diagnostic performance.
      RESULTS: US revealed significantly higher diagnostic performance than mammography
      for tumors larger than 2 cm. Combined reading showed significantly higher
      performance than mammography except for tumors smaller than 2 cm. The performance
      of all three tests was reduced in dense parenchyma, and significantly so for
      mammographic and combined interpretation. CONCLUSION: The accuracy of US in
      patients with palpable mammographically noncalcified and not obviously malignant
      breast tumors is lower than reported for mixed sample populations. The accuracy
      of US may be influenced by breast parenchyma density. Combined reading offers the
      highest diagnostic accuracy.

PMID- 10080729
TI  - Variability in the interpretation of ultrasonography in patients with palpable
      noncalcified breast tumors.
AB  - PURPOSE: To analyze interobserver variability of ultrasonography (US) as an
      adjunct to mammography in patients with palpable noncalcified breast tumors.
      MATERIAL AND METHODS: Mammographic, US, and combined reading of 200 patients with
      palpable noncalcified breast masses were performed independently by four
      experienced radiologists. Nonneoplastic abnormalities and mammographically
      obvious cancers were excluded. Receiver operating characteristic (ROC) analysis
      based on 115 tumors was carried out for mammography, US, and both combined for
      each radiologist. The US diagnoses of the 45 cancers excluded from ROC analysis
      and the 55 cancers included were compared. RESULTS: One radiologist revealed a
      significantly higher diagnostic performance with US than with mammography.
      Combined reading showed the highest performance for all observers, but the
      improvement as compared with mammography was significant for only two. Higher
      accuracy on combined reading was mainly caused by correct upgrading of tumors
      with benign or indeterminate mammographic findings. One radiologist had benefit
      of US for downgrading of tumors. All four radiologists made a malignant US
      diagnosis twice as often in mammographically obvious cancers than in
      mammographically nonconclusive tumors. CONCLUSION: Radiologists differ
      substantially in interpretation of breast imaging. Combined reading offers the
      highest diagnostic accuracy mainly by correct upgrading of tumors on US. The role
      of US for downgrading tumors is operator-dependent.

PMID- 10080730
TI  - Comparison of planar and SPECT scintimammography with 99mTc-sestamibi in the
      diagnosis of breast carcinoma.
AB  - PURPOSE: To compare results of planar and SPECT breast imaging with 99mTc-MIBI in
      detecting primary breast cancer. MATERIAL AND METHODS: Twenty-six consecutive
      patients with 34 suspected breast lesions underwent both planar and SPECT
      scintimammography. Ten minutes after injection of 700 MBq 99mTc-MIBI, 2 prone
      lateral projections were obtained, followed by a supine anterior projection.
      Forty minutes after injection, a SPECT study was done. All lesions were operated
      upon and verified with histopathology. RESULTS: A sensitivity of 85% and
      specificity of 88% of planar scintimammography in diagnosis of primary breast
      lesions were achieved. The corresponding values for SPECT were 61% and 64%.
      CONCLUSION: The diagnostic accuracy of planar scintimammography was not improved
      by using SPECT imaging.

PMID- 10080731
TI  - Thoracic CT findings in long-term hemodialysis patients.
AB  - PURPOSE: To evaluate thoracic CT findings of long-term hemodialysis patients.
      MATERIAL AND METHODS: Thoracic CT findings of 117 uremic patients (61 men, 56
      women) with complaints of cough, dyspnea, low-grade pyrexia, malaise, weight
      loss, and profuse perspiration were retrospectively documented. RESULTS:
      Atelectasis (60%), cardiomegaly (60%), pleural effusion (51%), vascular
      congestion (44%), parenchymal consolidation (38%), parenchymal scarring-fibrosis
      (31%), and lymphadenopathy (29%) were the most common CT findings in the thoraces
      of the long-term hemodialysis patients. Staphylococcus aureus was detected in 13
      patients (11%) who had parenchymal infiltration. Thoracic tuberculosis was
      identified in 15 patients (13%), 11 of these cases being confined to the lung
      parenchyma, 3 to the pleura, and 1 involving the pleura and pericardium.
      CONCLUSION: In patients under long-term hemodialysis treatment, parenchymal
      consolidation, secondary to infectious agents such as S. aureus and Mycobacterium
      tuberculosis, is the most important CT finding since these lesions can be
      detected and treated successfully if they are considered as etiologic factors
      early on.

PMID- 10080732
TI  - Internal mammary artery embolization for hemoptysis.
AB  - PURPOSE: The purpose of this study was to determine the factors influencing
      development of blood supply from the internal mammary artery and to discuss the
      value of embolization of the abnormal branches from this vessel using small
      particles following occlusion of the normal distal branches using microcoils in
      treating hemoptysis. MATERIAL AND METHODS: Five patients with hemoptysis
      underwent internal mammary artery embolization with coaxial microcatheter
      systems. Bronchoscopy, chest radiographs, and CT were performed to determine the
      site and extent of the basic disease before embolotherapy in all patients.
      RESULTS: In all patients, pulmonary lesions had extended from the lung to the
      adjacent pleural surface at the anterior lung field. Four patients underwent
      embolization from the proximal portion of the internal mammary artery following
      distal coil embolization. One patient who underwent only proximal embolization
      had recurrent bleeding. CONCLUSION: The internal mammary artery contributes to
      the perfusion of lesions responsible for hemoptysis when the basic lesion
      involves the pulmonary parenchyma adjacent to the anterior pleural surface.
      Initial distal occlusion of the internal mammary artery may improve the efficacy
      of embolization of this artery for hemoptysis.

PMID- 10080733
TI  - CT in malignancy grading and prognostic prediction of non-Hodgkin's lymphoma.
AB  - PURPOSE: The presence of tumor inhomogeneities in MR images of non-Hodgkin's
      lymphoma (NHL) provides information about malignancy grade and prognosis. The aim
      of this study was to determine whether CT images are also informative in these
      respects. MATERIAL AND METHODS: Sixty-three CT examinations in patients with NHL
      (32 high-grade and 31 low-grade tumors) were reviewed retrospectively by two
      senior radiologists. The tumor patterns were classified subjectively as
      homogeneous, slightly inhomogeneous or severely inhomogeneous and their relations
      to malignancy grade, clinical characteristics and prognosis were determined.
      RESULTS: Sixteen out of 17 patients with a severely inhomogeneous tumor pattern
      had high-grade NHL tumors while 21 out of 29 patients with a homogeneous tumor
      appearance had low-grade NHL tumors. Among chemotherapy-treated patients, those
      with the highest degree of inhomogeneity had a significantly worse prognosis (9
      out of 11 patients died). This relationship was not found in patients treated
      with radiotherapy. CONCLUSION: A severely inhomogeneous tumor pattern on CT
      images was found to be associated with a high malignancy grade in NHL. This CT
      pattern was also compatible with a poor prognosis in patients treated with
      chemotherapy.

PMID- 10080734
TI  - MR pyelography and conventional MR imaging in urinary tract obstruction.
AB  - PURPOSE: To evaluate the possible role of MR imaging in the assessment of
      patients with urinary tract obstruction by combining conventional MR imaging and
      MR pyelography (MRP). MATERIAL AND METHODS: Forty-three patients with dilated
      upper urinary tract were studied with a high gradient strength 0.5 T magnet.
      Respiratory compensated T1-weighted, SE and T2-weighted TSE sequences were
      acquired in all patients. MRP images were obtained by using a respiratory
      compensated 3D T2-weighted TSE sequence. MRP images were reconstructed with a MIP
      algorithm. In all cases, urography and/or ascending pyelography were also
      performed. Images were independently evaluated by two radiologists. RESULTS: The
      dilated tract ureter and the level of the obstruction could be correctly
      demonstrated in all cases. The cause of the obstruction was correctly
      demonstrated by examiner 1 in 90% and by examiner 2 in 88%. The interobserver
      agreement was high with a kappa-value of 0.96. CONCLUSION: In cases of
      obstructive hydroureteronephrosis MR imaging, combining MRP and conventional
      sequences, can be proposed as an accurate technique in the assessment of level
      and cause of obstruction.

PMID- 10080735
TI  - Renal diuretic duplex Doppler sonography in childhood hydronephrosis.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic value of
      diuretic duplex Doppler sonography in distinguishing between obstructive and
      nonobstructive hydronephrosis in children by calculating the resistive indices
      (RI) before and after administration of furosemide. MATERIAL AND METHODS: We
      prospectively evaluated 28 kidneys (2 solitary) in 15 patients with unilateral or
      bilateral neonatal hydronephrosis. All patients underwent diuretic renography and
      duplex Doppler sonography before and after administration of furosemide. RESULTS:
      According to the half-time drainage patterns at diuretic renography, 13 kidneys
      were classified as nonobstructed and 15 as obstructed. At baseline, the mean RI
      values of nonobstructed and obstructed kidneys were not significantly different
      (0.66 and 0.64, respectively). Ten minutes after the injection of furosemide, the
      mean RI values of the nonobstructed and obstructed kidneys were 0.68 and 0.70,
      respectively. The increase in RI over the baseline 10 min after the diuretic
      injection was statistically significant (p<0.00001) in the obstructed kidneys.
      CONCLUSION: The baseline RI value of 0.70 is not a definite value for
      distinguishing obstructed from nonobstructed systems. An increase in RI of at
      least 10% over the baseline seems to be a more reliable criterion, especially
      when it is used in conjunction with diuretic renography.

PMID- 10080736
TI  - Saline-jet aspiration thrombectomy catheter. Clinical results in patients with
      venous thrombosis.
AB  - PURPOSE: To evaluate hydraulic thrombectomy using a saline-jet aspiration
      thrombectomy catheter in the treatment of venous thrombosis. MATERIAL AND
      METHODS: Ten patients underwent 12 hydraulic thrombectomy procedures using 2.7 or
      4.0 mm catheters. The site of the thrombus was either central, peripheral or in
      portal veins. The age of the thrombi was between 2 and 60 days (mean 19.7 days).
      The efficacy of hydraulic thrombectomy was evaluated based on the aspirated
      thrombus ratio (ATR), i.e. the volume of the thrombus aspirated divided by the
      volume of the thrombus before thrombectomy. ATR was estimated by comparing the
      angiograms of the lesion before and after thrombectomy. RESULTS: Soft thrombi
      were usually rapidly removed. ATR was >2/3 in 3, 2/3-1/3 in 2, 1/3-0 in 4, and 0
      in 1 patient. The activation time of the injector was 23-224 s (mean 102 s) and
      the volume of aspirated blood was 30-680 ml (mean 250 ml). Compensatory infusion
      of saline was performed for blood loss, and 400 ml of packed red blood cells was
      transfused in 1 patient. No complications of the hydraulic thrombectomy were
      observed. Thrombolysis or additional treatment were performed in 9 patients.
      CONCLUSION: Hydraulic thrombectomy using this catheter can contribute to the
      treatment of venous thrombosis.

PMID- 10080737
TI  - A method to evaluate the performance of X-ray imaging scintillators by means of
      the brightness-sharpness index (BSI).
AB  - PURPOSE: To propose an image quality index, the brightness-sharpness index (BSI),
      for assessing the quality of the image produced by phosphors of medical imaging
      detectors. MATERIAL AND METHODS: BSI was evaluated by experimental X-ray
      luminescence and modulation transfer function measurements. BSI was determined
      for a number of test phosphor screens prepared from Gd2O2S:Tb, La2O2S:Tb, and
      Y2O2S:Tb phosphor materials. The screens covered a wide range of coating
      thicknesses from 50 to 150 mg/cm2 and measurements were performed for X-ray tube
      voltages between 50 and 120 kVp. RESULTS: Gd2O2S:Tb phosphor exhibited higher
      brightness and sharpness, as compared to the other phosphor materials, for all
      screens and X-ray tube voltages used. Best Gd2O2S:Tb performance was observed for
      thin screens and high tube voltages. La2O2S:Tb exhibited higher BSI values than
      Y2O2S:Tb for medium and high tube voltages. CONCLUSION: Results showed that
      phosphor materials of high X-ray detection and X-ray-to-light conversion
      properties exhibit high BSI values indicating that BSI may provide a means of
      phosphor performance evaluation for imaging applications.

PMID- 10080738
TI  - Epithelioid hemangioendothelioma with solitary bone location associated to
      multiple lung and liver lesions. A case report.
AB  - Progressive development of a lobulated osteolytic lesion of the left calcaneus
      was observed in a 28-year-old woman. The bone tumor was associated with multiple
      lung nodules and later with a few small nodular liver lesions. A histological and
      immunochemical diagnosis of epithelioid hemangioendothelioma was obtained by bone
      tumor resection and thoracoscopic lung biopsy. Imaging aspects are reported with
      emphasis on its multifocality.

PMID- 10080739
TI  - Clearance of iopromide during haemodialysis with high- and low-flux membranes.
AB  - PURPOSE: The present clinical trial addressed the clearance of the contrast
      medium iopromide, a middle-sized molecule, during dialysis with high- and low
      flux membranes. MATERIAL AND METHODS: Twenty chronic haemodialysis patients
      without residual renal function were dialysed either with low-flux haemophan or
      high-flux polyamide directly after application of the contrast medium. Iodine
      concentrations were determined by radiofluorescence methods. RESULTS: Plasma
      concentrations of iodine before dialysis ranged between 1.1 and 3.9 mg/ml. The
      mean clearance rates for both membranes were comparable (110+/-1.4 ml/min high
      flux and 108+/-1.9 ml/min low-flux), the sieving-coefficient was 0.83 for both
      membranes. After three hours of dialysis, 58% (high-flux) and 62% (low-flux) of
      iopromide was removed, half time of elimination was reached after 140+/-16 min
      (high-flux) and 122+/-11 min (low-flux). CONCLUSION: Our results demonstrated
      that elimination of iopromide is not dependent on the pore size of the membrane
      during dialysis. Due to higher blood flow rate, we found a higher elimination
      rate and a reduced half-time of elimination than prior investigations.

PMID- 10080740
TI  - Concentration of 123I-metaiodobenzylguanidine in left and right liver lobes.
      Findings indicate regional differences in function in the normal liver.
AB  - PURPOSE: Normal radioactivity in the liver is often shown to be higher in the
      left lobe than in the right lobe at clinical examination by single photon
      emission computed tomography (SPECT) with 123I-metaiodobenzylguanidine (123I
      MIBG). Our objective was to determine whether this represents a pathological
      condition. MATERIAL AND METHODS: The distribution of 123I-MIBG in the liver was
      retrospectively studied in clinical patients who had normal CT examinations of
      the liver and spleen. In the SPECT sections of 27 123I-MIBG examinations, we
      determined the activity ratios between the left and right lobes. The control
      group comprised 33 examinations with (111)In-pentetreotide (OctreoScan) and 23
      examinations with 99mTc-antigranulocyte antibody. RESULTS: The mean activity
      ratio between left and right lobes for 123I-MIBG was 1.24, and for (111)In
      pentetreotide 0.87. These figures differed significantly both from each other and
      from 1.00. The mean ratio for 99mTc-antibody at the early examinations was 0.99,
      and at the late examinations 0.95. These figures differed significantly from the
      values for 123I-MIBG and (111)In-pentetreotide. CONCLUSION: The increased
      concentration of 123I-MIBG in the left lobe of the liver compared to the right
      lobe is a normal finding. The reason for this cannot be explained. The difference
      in the way in which the left and right lobes deal with the three
      radiopharmaceuticals is a new finding and indicates a regional difference in
      liver function that has not been reported previously.

PMID- 10080741
TI  - Reply 

PMID- 10080825
TI  - Are immunological mechanisms relevant for the development of atherosclerosis?

PMID- 10080826
TI  - CD30 in normal and neoplastic cells.
AB  - In 1982 Stein and coworkers identified a new molecule, CD30 (Ki-1), which is
      expressed by Reed-Sternberg (RS) cells of Hodgkin's Disease (HD) (1). Although
      CD30 is not a specific RS cell marker, its characterization has assumed an
      important role not only in the differential diagnosis of HD, but also in the
      identification of a morphologically and clinically distinct type of large cell
      lymphoma, now designated as anaplastic large cell lymphoma (ALCL) (2). The
      cloning of human and murine CD30 and the utilization of genetically manipulated
      animal models have rapidly expanded our knowledge on its physiological role in
      lymphoid development and differentiation. The goal of this review is to present
      an overview of this rapidly evolving field and discuss the role of CD30 in normal
      and neoplastic lymphoid cells.

PMID- 10080827
TI  - Antibodies to oxidized LDL and LDL-containing immune complexes as risk factors
      for coronary artery disease in diabetes mellitus.
AB  - Several groups have published results from clinical studies supporting the
      involvement of anti-modified LDL antibodies as risk factors for the initiation or
      progression of cardiovascular disease. However, the data published so far are
      judged inconclusive because of several contradictory observations concerning the
      correlation between clinical evidence of arteriosclerosis and the levels of
      antibodies to oxidized LDL (oxLDL Ab). We have previously reported that oxLDL Ab
      exist both in free form and as antigen-antibody complexes (LDL-IC) in patients
      with insulin-dependent diabetes mellitus (IDDM). The presence of LDL-IC in IDDM
      patients has important implications: it may interfere with the assay of oxLDL
      antibodies and the levels of LDL-IC may correlate better with the development of
      arteriosclerosis than the levels of free oxLDL antibodies. To clarify these
      questions baseline samples collected from 49 IDDM patients, who subsequently
      developed coronary artery disease (CAD) during an 8-year follow-up period, were
      compared to baseline samples from 49 age-, sex-, and duration-matched control
      IDDM subjects who remained free of clinical CAD during an identical follow-up
      period. The levels of free oxLDL antibody were significantly lower in the
      patients who developed CAD. The same patients had significantly higher
      concentrations of total cholesterol, apolipoprotein B, and IgA in immune complex
      enriched polyethylene glycol (PEG) precipitates. The concentration of IgG was
      also higher in PEG precipitates from patients who developed CAD, but did not
      reach statistical significance. This indicates that patients who develop CAD had
      higher levels of circulating LDL-IC, a fact that could not be deduced from the
      measurement of free oxLDL antibody concentrations. A linear regression analysis
      of the correlation between the concentrations of total cholesterol in PEG
      precipitates, taken as a surrogate measurement of PEG-precipitated oxLDL-IC, and
      the concentration of free oxLDL antibody in serum showed a statistically
      significant negative correlation (r = -0.229, P = 0. 024). Our results support
      the conclusion that oxLDL-IC may be a risk factor for the development of
      macrovascular disease in IDDM patients. We also have demonstrated that
      circulating oxLDL-IC interfere with the assay of free oxLDL antibodies.

PMID- 10080828
TI  - Conditioned immune response to interferon-gamma in humans.
AB  - We determined whether a classical conditioning paradigm may be used to condition
      immunologic responses in normal human subjects receiving an optimal
      immunostimulating dose of recombinant human interferon-gamma (rhIFN-gamma). We
      conducted a placebo-controlled, double-blind study of 31 normal volunteers in
      order to determine whether an initially immune-neutral stimulus, oral propylene
      glycol (PG), could eventually elicit an immune response as a consequence of its
      being paired with a known immunostimulatory dose and schedule of rhIFN-gamma.
      Subjects were randomly assigned to one of three groups: (A) rhIFN-gamma
      injections paired with PG; (B) normal saline injections paired with PG; (C) rhIFN
      gamma injections alone. During the 4-week study, subjects received progressively
      fewer injections so that, by the final week of the study, no injections were
      given and groups A and B received only PG. The principal outcome measures were
      serum concentrations of quinolinic acid (QUIN) and neopterin, two nonspecific but
      sensitive markers of immune activation, and expression of Fc receptors (CD64) on
      peripheral blood mononuclear cells. RhIFN-gamma injections produced significant
      and predictable alterations in each of the measured immune parameters. No group B
      subject made an immune response. Mean serum QUIN levels were significantly higher
      at the end of week three for subjects in the experimental condition (group A)
      than for subjects receiving rhIFN-gamma alone (group C) despite receiving
      identical doses of rhIFN-gamma. Similarly, the predicted decay in mean serum
      neopterin levels from the end of week 1 to the end of week 2 was seen in group C
      but not in group A. The exposure of group A to PG blunted the decline of CD64
      expression in week four. The data suggest that the pairing of an unconditioned
      stimulus (rhIFN-gamma) and a conditioned stimulus (PG) permits the conditioned
      stimulus alone to prolong a cytokine-induced response in normal humans.

PMID- 10080829
TI  - Anticentromere autoantibodies in patients without Raynaud's disease or systemic
      sclerosis.
AB  - Anticentromere autoantibodies (ACA) are associated with Raynaud's disease and
      systemic sclerosis (SSc). ACA usually bind at least one of three major centromere
      proteins (CENPs), particularly CENP-B. We identified 16 patients with ACA who do
      not have Raynaud's disease or SSc. The objective of this study was to determine
      whether these 16 ACA differ in antigenic specificity from the ACA found in
      patients with Raynaud's disease or SSc. Binding of these serum ACA was tested
      using competition experiments with recombinant CENP-B, and native centromere
      proteins from HEp-2 cells and HeLa nuclear extracts in ELISAs, immunoblots, and
      indirect immunofluorescence assays. The ACA from these 16 patients are strikingly
      different from those obtained from patients who have Raynaud's disease or SSc.
      Only 5 of the 16 index sera (31.25%) bound CENP-B from two or more different
      sources by at least two methods. Six of these 16 sera (37.5%) did not bind CENP-B
      on ELISA, and 8 of 16 (43.75%) did not bind CENP-B on immunoblots. Three sera did
      not bind CENP-B either by ELISA or immunoblots. Of the 13 sera that bound CENP-B,
      their patterns of binding to CENP-B strongly suggested that they bind different
      epitopes within the CENP-B antigen. Independently of their binding to CENP-B,
      these sera reacted mainly with minor CENP antigens detected by HeLa nuclear
      extracts. We have identified unusual ACA not associated with Raynaud's disease or
      SSc.

PMID- 10080830
TI  - Activation of nitric oxide signaling through muscarinic receptors in
      submandibular glands by primary Sjogren syndrome antibodies.
AB  - Primary Sjogren Syndrome is a chronic autoimmune disease characterized by
      exocrine gland dysfunction. Here we present evidence of the activation of nitric
      oxide signaling cascade by circulating antibodies of patients with Sjogren
      Syndrome in rat submandibular glands. Constitutive nitric oxide synthase and
      cyclic GMP levels are modulated by Sjogren IgGs through the activation of
      muscarinic acetylcholine receptors on the glands. The effects are similar to
      those produced by the agonist carbachol and blocked by the antagonist atropine.
      The involvement of M1 subtype of muscarinic receptors is proposed since both a
      synthetic peptide homologous to an extracellular domain of M1 receptor and
      pirenzepine, a selective M1 antagonist, partially blocked the effects. We
      conclude that Sjogren Syndrome antibodies can activate nitric oxide signaling in
      submandibular glands by interacting with muscarinic acetylcholine receptors.

PMID- 10080831
TI  - Expression of adhesion molecules in chronic serum sickness in rats.
AB  - Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness
      (CSS). We therefore studied the expression of CD54 and its ligands CD18 and
      CD11b/c in CSS in 10 rats with CSS, 6 rats immunized similarly who did not
      developed proteinuria (no-CSS group), and 10 normal rats (control group). Intense
      (6 to 35 times more than controls) leukocyte infiltration was observed in CSS.
      The CSS group over-expressed CD54 in glomeruli and interstitium in association
      with increments in CD18- and CD11b/c-positive cells ranging 2.5 to 7 times the
      number found in controls. 75% of infiltrating leukocytes expressed CD18 and 87%
      expressed CD11b/c. The non-CSS group had leukocyte infiltration and expression of
      adhesion molecules similar to control group. Adherence of CD43-positive cells to
      renal tissues was 4 times higher in renal tissue from CSS rats than to normal
      kidney. Pretreatment with corresponding Mabs reduced adherence by half. We
      concluded that over-expression of CD54 and its ligands CD18 and CD11b/c in
      infiltrating leukocytes occur in CSS. Binding experiments suggest the functional
      relevance of these molecules.

PMID- 10080832
TI  - Antibody-dependent cell-mediated cytotoxicity can protect PBMC from infection by
      cell-associated HIV-1.
AB  - We have developed a novel in vitro assay system to study the role of antibody
      dependent cell-mediated cytotoxicity (ADCC) in protection against HIV-1 infection
      by cell-associated virus. HIV-1-infected NK-resistant cells are mixed with
      specific antibody and unstimulated PBMC and ADCC is allowed to occur over several
      hours. The PBMC are then activated and cultured to allow virus replication in
      newly infected T cells. To ensure that ADCC is the only mechanism by which
      protection could occur we have used haptenated (TNP) infected cells and anti
      hapten antibody. Anti-hapten sera completely protected PBMC from infection by
      haptenated HIV-1-infected cells in ADCC protection assays. F(ab')2 fragments of
      anti-hapten IgG showed no protection, confirming that ADCC was responsible for
      protection by anti-hapten IgG. PCR analysis for HIV-1 DNA confirmed the
      elimination of infected cells. We believe this to be the first direct
      demonstration that ADCC alone can protect PBMC from infection by cell-associated
      HIV-1.

PMID- 10080833
TI  - Role of cytomegalovirus in the T cell changes seen in elderly individuals.
AB  - The effect of prior cytomegalovirus (CMV) infection on the immune system was
      evaluated in young and elderly volunteers. Prevalence of IgG antibodies to CMV
      was higher in the elderly volunteers. In both age groups, there was a strong
      association with CMV seropositivity and increased number of CD28- CD4 or CD8 T
      cells, as well as with increased numbers of T cells expressing CD56 or DR.
      Although these changes have previously been reported to be age-related, they were
      independent of age when CMV serological status was taken into account. In
      contrast, both age group and CMV status were important determinants of the total
      number of T cells, the number of CD8 T cells, and the number of CD8 T cells
      expressing CD45RA or CD28. These findings indicate that prior infection with CMV,
      as reflected by CMV serological status, has important effects on T cell subsets
      and surface markers and must be considered whenever evaluating age-related
      changes in immunological parameters.

PMID- 10080834
TI  - Evidence of indirect allorecognition in long-term human renal transplantation.
AB  - The purpose of this study was to investigate indirect alloreactivity in the
      peripheral blood of long-term renal transplanted patients. We evaluated the T
      cell proliferative response to a whole pool of donor cell-derived allopeptides,
      processed and presented by host antigen-presenting cells (APC), rather than to
      synthetic peptides. For the indirect pathway, proliferation assays were performed
      using APC-depleted donor cells. Indirect alloreactivity was detected in 57%
      (8/14) of the patients, 6 of whom presented no evidence of rejection, but 2
      patients had a diagnosis of chronic rejection. In 4 of 8 positive cases (50%),
      proliferation was detected with 5 days of culture, and sometimes indirect
      alloresponse was the dominant route. We present evidence that the indirect
      alloproliferative response to a pool of naturally processed donor peptides is
      present in the peripheral blood of long-term renal transplanted patients
      irrespective of rejection.

PMID- 10080835
TI  - Evaluation of lymphocytic responses after treatment with Bacillus Calmette-Guerin
      and interferon-alpha 2b for superficial bladder cancer.
AB  - Bladder wash-derived lymphocytes from superficial bladder cancer patients
      involved in high dose BCG, low dose BCG, and low dose BCG with IFN-alpha
      treatments were examined. We found an increasing trend in the percentage of CD3 T
      cells with each weekly intravesical instillation and the proportion of CD3 T
      cells expressing the gammadelta T cell receptor was significantly higher in
      patients receiving standard dose BCG than those receiving low dose BCG or low
      dose BCG plus IFN-alpha. Most patients had a predominance of CD4 T cells, while
      some had more CD8 T cells. The CD4/CD8 ratio did not vary much during the
      instillations. Surprisingly, both patients and normal control individuals had
      high percentages of CD69- and CD45RO-positive lymphocytes in the bladder wash and
      this was not reflected in lymphocytes from peripheral blood collected in
      parallel. We found no differences in lymphocyte phenotypes, cytokine production,
      and clinical outcome in the patients from three arms. This may reflect that the
      qualitative and quantitative immune responses elicited from the three treatments
      are similar. However, the lymphokine-activated killing ability of peripheral
      blood lymphocytes against allogeneic cell-lines from the cancer patients was
      depressed compared to normal individuals and the cytotoxicity appeared to be
      enhanced after intravesical treatment.

PMID- 10080836
TI  - The prognostic significance in HIV infection of immune activation represented by
      cell surface antigen and plasma activation marker changes.
AB  - One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control
      seronegative homosexual men were assessed for 23 parameters reflecting immune
      activation to determine prognostic significance for occurrence of AIDS. Samples
      cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid
      1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR,
      CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor
      alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and
      beta2-microglobulin. Using a proportional hazards model, prognostic markers
      included decreased CD4 number and percentage; increased sIL-2R, neopterin, and
      beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased
      CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and
      CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After
      adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells
      remained significant, indicating that additional information about AIDS risk was
      provided by these markers.

PMID- 10080837
TI  - C1q autoantibodies in HIV infection: correlation to elevated levels of
      autoantibodies against 60-kDa heat-shock proteins.
AB  - Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from
      132 HIV-infected subjects and in sera from 140 HIV-seronegative healthy
      individuals as control. An ELISA method applied for the determination of C1qAb in
      other diseases was used. In part of these sera, other autoantibodies (antibodies
      reacting with 60-kDa human heat shock protein (hsp60) or mycobacterial hsp65; IgA
      and IgG class antibodies against the Fab and F(ab')2 moieties of IgG) as well as
      complement-mediated antibody-dependent enhancement/neutralization (C'-ADE) were
      also determined. Increased amount of C1qAb was found in HIV-infected subjects as
      compared with HIV-seronegative controls (P = 0.0138). In 17 of 132 (13.0%)
      seropositive individuals but only in 7/140 (5.0%) samples from the controls, the
      amount of C1qAb exceeded the upper limit (95th percentile) of the normal values
      (P = 0.031). The amount of C1qAb significantly decreased during a follow-up
      period of 65 months. C1qAb levels were found to strongly correlate to hsp60/65
      autoantibodies but did not correlate or only weakly correlated to the amount of
      anti-Fab or anti-F(ab')2 autoantibodies measured in the same serum samples. Anti
      C1q antibodies recognized the solid phase hsp60/65. Three predicted epitope
      regions of M. paratuberculosis hsp65 were able to bind efficiently C1q
      antibodies. An inverse correlation was found between C1qAb and C'-ADE,
      neutralization was more frequent in the sera with detectable C1qAb, whereas sera
      without C1qAb more likely enhanced HIV infection in vitro.

PMID- 10080838
TI  - Involvement of nitric oxide in protecting mechanism during experimental
      cryptococcosis.
AB  - In the present study we investigated the role of nitric oxide (NO) in the
      effector mechanisms of host defense against Cryptococcus neoformans in vivo. Our
      results showed an increase of NO produced by the peritoneal macrophages from 14
      days infected rats compared with normal rats. These cells were capable of killing
      C. neoformans to a greater extent than macrophages from noninfected rats (80% vs
      20%, respectively). The killing of C. neoformans by infected cells was
      efficiently inhibited (80% to 35%, P < 0.001) by adding aminoguanidine (AG) to
      the cultures. We observed that in vivo administration of AG to the infected
      animals efficiently inhibited the metabolism producing NO and failed to affect
      that of normal animals. When the NO synthase (NOS) was inhibited in vivo in the
      infected animals, a marked increase of the fungi charge in the organs was
      observed with respect to the normal animals treated with AG. We also observed
      that the course of the infection is drastically modified after the inhibition of
      NO production because all the animals infected and treated with AG died from
      cryptococcosis before 20 days postinfection (p.i.). These results indicate that
      NO is a crucial molecule in the effector mechanisms in this infection model.

PMID- 10080839
TI  - Antiinflammatory effects of soluble complement receptor type 1 promote rapid
      recovery of ischemia/reperfusion injury in rat small intestine.
AB  - We examined the effect of soluble complement receptor type 1 (sCR1) on mucosal
      injury and inflammation in a rat model of ischemia/reperfusion. Groups of vehicle
      and sCR1-treated rats underwent 30 min of mesenteric ischemia followed by 60 or
      120 min of reperfusion. When compared to vehicle-treated rats, treatment with
      sCR1 (12 mg/kg) prior to 120 min of reperfusion significantly reduced mucosal
      injury, neutrophil infiltration, leukotriene B4 production, and restored villus
      height to control levels. The protective effect of sCR1 evident at 120 min of
      reperfusion was not observed at 60 min of reperfusion despite rapid inactivation
      of complement. These data suggest that complement inhibition minimized mucosal
      disruption by facilitating mucosal restitution or interrupting the inflammatory
      process. Delayed administration of sCR1 for 30 or 60 min into the reperfusion
      period progressively reduced the protection. sCR1-mediated rapid recovery of rat
      intestine after ischemia/reperfusion underscores the fundamental role of
      complement activation in neutrophil-mediated tissue injury.

PMID- 10080840
TI  - Progression to type 1 diabetes is associated with a change in the immunoglobulin
      isotype profile of autoantibodies to glutamic acid decarboxylase (GAD65).
      Childhood Diabetes in Finland Study Group.
AB  - To investigate whether type 1 diabetes in man is associated with a preferential
      Th1/Th2 response, and whether autoantibodies to one of the main autoantigens
      would reflect such a response, we characterized the immunoglobulin isotype
      profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings
      to IDDM patients. Samples obtained from affected subjects before and at clinical
      onset of IDDM, from unaffected individuals at high risk and at low risk and from
      healthy controls were studied. The immunoglobulin isotype profile in the siblings
      at low risk reflected a more immature, i.e., IgM and Th2 like, i.e., IgE response
      compared to the progressors and siblings at high risk, with significantly higher
      median levels of IgM and IgE. The rank order of anti-GAD65 immunoglobulin
      isotypes was similar in the siblings before and at clinical onset of IDDM, IgG1 >
      IgG4 > IgM > IgE > IgA > IgG3 > IgG2, but markedly different in the individuals
      at low risk, IgG1 > IgM > IgE > IgG4 > IgG3 > IgA > IgG2. Based on these
      observations, we suggest that progression to clinical onset of IDDM is associated
      with a maturation and a decrease in the Th2 immune response against GAD65;
      findings which could have implications for future intervention and prediction
      strategies.

PMID- 10080841
TI  - Volume 87, number 1 (1998), in article no. II974515, "A newly discovered function
      for C1 inhibitor, removal of the entire c1qr2s2 complex from immobilized human
      IgG Subclasses," by chang-hung chen and robert J. Boackle, pages 68-74 

PMID- 10080842
TI  - Second joint meeting of the clinical immunology society and the clinical
      immunology committee of the international union of immunological societies 

PMID- 10080843
TI  - Preformulation study of the vaccine candidate P64k against Neisseria
      meningitidis.
AB  - We have previously isolated, cloned and expressed in Escherichia coli the lpdA
      gene coding for a high-molecular-mass protein (P64k) common to many meningococcal
      strains. P64k is an outer membrane lipoamide dehydrogenase that is highly
      immunogenic in animals. Here we describe a preformulation study of the
      recombinant protein as a vaccine candidate against Neisseria meningitidis, in
      which six variants containing the candidate were tested. Three assays were used
      to identify the most suitable variant for further evaluation: percentage of
      adsorption, identification of P64k by SDS/PAGE, and immunogenicity in mice. All
      the preformulation variants studied showed more than 98% of adsorption of P64k on
      the aluminium gel. After desorption, P64k was also identified by SDS/PAGE in the
      six preformulation variants. Seroconversion was attained in all groups analysed.
      On the basis of these results, the most effective variant consisted of 20
      microg/ml P64k plus 0.5 mg/ml aluminium hydroxide.

PMID- 10080844
TI  - Symptomatic gastroesophageal reflux as a risk factor for esophageal
      adenocarcinoma.
AB  - BACKGROUND: The causes of adenocarcinomas of the esophagus and gastric cardia are
      poorly understood. We conducted an epidemiologic investigation of the possible
      association between gastroesophageal reflux and these tumors. METHODS: We
      performed a nationwide, population-based, case-control study in Sweden. Case
      ascertainment was rapid, and all cases were classified uniformly. Information on
      the subjects' history of gastroesophageal reflux was collected in personal
      interviews. The odds ratios were calculated by logistic regression, with
      multivariate adjustment for potentially confounding variables. RESULTS: Of the
      patients interviewed, the 189 with esophageal adenocarcinoma and the 262 with
      adenocarcinoma of the cardia constituted 85 percent of the 529 patients in Sweden
      who were eligible for the study during the period from 1995 through 1997. For
      comparison, we interviewed 820 control subjects from the general population and
      167 patients with esophageal squamous-cell carcinoma. Among persons with
      recurrent symptoms of reflux, as compared with persons without such symptoms, the
      odds ratios were 7.7 (95 percent confidence interval, 5.3 to 11.4) for esophageal
      adenocarcinoma and 2.0 (95 percent confidence interval, 1.4 to 2.9) for
      adenocarcinoma of the cardia. The more frequent, more severe, and longer-lasting
      the symptoms of reflux, the greater the risk. Among persons with long-standing
      and severe symptoms of reflux, the odds ratios were 43.5 (95 percent confidence
      interval, 18.3 to 103.5) for esophageal adenocarcinoma and 4.4 (95 percent
      confidence interval, 1.7 to 11.0) for adenocarcinoma of the cardia. The risk of
      esophageal squamous-cell carcinoma was not associated with reflux (odds ratio,
      1.1; 95 percent confidence interval, 0.7 to 1.9). CONCLUSIONS: There is a strong
      and probably causal relation between gastroesophageal reflux and esophageal
      adenocarcinoma. The relation between reflux and adenocarcinoma of the gastric
      cardia is relatively weak.

PMID- 10080845
TI  - Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for
      Toxic Alcohols Study Group.
AB  - BACKGROUND: Ethylene glycol poisoning causes metabolic acidosis and renal failure
      and may cause death. The standard treatment is inhibition of alcohol
      dehydrogenase with ethanol, given in intoxicating doses, and adjunctive
      hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol
      dehydrogenase, in the treatment of ethylene glycol poisoning. METHODS: We
      administered intravenous fomepizole to 19 patients with ethylene glycol poisoning
      (plasma ethylene glycol concentration, > or =20 mg per deciliter [3.2 mmol per
      liter]). Patients who met specific criteria also underwent hemodialysis.
      Treatment was continued until plasma ethylene glycol concentrations were less
      than 20 mg per deciliter. Acid-base status, renal function, the kinetics of
      fomepizole, and ethylene glycol metabolism were assessed at predetermined
      intervals. RESULTS: Fifteen of the patients initially had acidosis (mean serum
      bicarbonate concentration, 12.9 mmol per liter). Acid-base status tended to
      normalize within hours after the initiation of treatment with fomepizole. One
      patient with extreme acidosis died. In nine patients, renal function decreased
      during therapy; at enrollment, all nine had high serum creatinine concentrations
      and markedly elevated plasma glycolate concentrations (> or =97.7 mg per
      deciliter [12.9 mmol per liter]). None of the 10 patients with normal serum
      creatinine concentrations at enrollment had renal injury during treatment; all 10
      had plasma glycolate concentrations at or below 76.8 mg per deciliter (10.1 mmol
      per liter). Renal injury was independent of the initial plasma ethylene glycol
      concentration. The plasma concentration of glycolate and the urinary excretion of
      oxalate, the major metabolites of ethylene glycol, uniformly fell after the
      initiation of fomepizole therapy. Few adverse effects were attributable to
      fomepizole. CONCLUSIONS: In patients with ethylene glycol poisoning, fomepizole
      administered early in the course of intoxication prevents renal injury by
      inhibiting the formation of toxic metabolites.

PMID- 10080846
TI  - Atrial arrhythmia after surgical closure of atrial septal defects in adults.
AB  - BACKGROUND: Atrial flutter and atrial fibrillation are causes of morbidity in
      adults with an atrial septal defect. In this study, we attempted to identify risk
      factors for atrial flutter and fibrillation both before and after the surgical
      closure of an atrial septal defect. METHODS: We searched for preoperative and
      postoperative atrial flutter or fibrillation in 213 adult patients (82 men and
      131 women) who underwent surgical closure of atrial septal defects because of
      symptoms, a substantial left-to-right shunt (ratio of pulmonary to systemic blood
      flow, >1.5:1), or both at Toronto Hospital between 1986 and 1997. RESULTS: Forty
      patients (19 percent) had sustained atrial flutter or fibrillation before
      surgery. As compared with the patients who did not have atrial flutter or
      fibrillation before surgery, those who did were older (59+/-11 vs. 37+/-13 years,
      P<0.001) and had higher mean pulmonary arterial pressures (25.0+/-9.7 vs. 19.7+/
      8.2 mm Hg, P=0.001). There were no perioperative deaths. After a mean follow-up
      period of 3.8+/-2.5 years, 24 of the 40 patients (60 percent) continued to have
      atrial flutter or fibrillation. The mean age of these patients was greater than
      that of the 16 who converted to sinus rhythm (P=0.02). New-onset atrial flutter
      or atrial fibrillation was more likely to have developed at follow-up in patients
      who were older than 40 years at the time of surgery than in those who were 40 or
      younger (5 of 67 vs. 0 of 106, P=0.008). Late events (those occurring more than
      one month after surgery) included stroke in six patients (all but one with atrial
      flutter or fibrillation, one of whom died) and death from noncardiac causes in
      two patients. Multivariate analysis showed that older age (>40 years) at the time
      of surgery (P=0.001), the presence of preoperative atrial flutter or fibrillation
      (P<0.001), and the presence of postoperative atrial flutter or fibrillation or
      junctional rhythm (P=0.02) were predictive of late postoperative atrial flutter
      or fibrillation. CONCLUSIONS: The risk of atrial flutter or atrial fibrillation
      in adults with atrial septal defects is related to the age at the time of
      surgical repair and the pulmonary arterial pressure. To reduce the morbidity
      associated with atrial flutter and fibrillation, the timely closure of atrial
      septal defects is warranted.

PMID- 10080847
TI  - The association between sleep apnea and the risk of traffic accidents.
      Cooperative Group Burgos-Santander.
AB  - BACKGROUND AND METHODS: Drowsiness and lack of concentration may contribute to
      traffic accidents. We conducted a case-control study of the relation between
      sleep apnea and the risk of traffic accidents. The case patients were 102 drivers
      who received emergency treatment at hospitals in Burgos or Santander, Spain,
      after highway traffic accidents between April and December 1995. The controls
      were 152 patients randomly selected from primary care centers in the same cities
      and matched with the case patients for age and sex. Respiratory polygraphy was
      used to screen the patients for sleep apnea at home, and conventional
      polysomnography was used to confirm the diagnosis. The apnea-hypopnea index (the
      total number of episodes of apnea and hypopnea divided by the number of hours of
      sleep) was calculated for each participant. RESULTS: The mean age of the
      participants was 44 years; 77 percent were men. As compared with those without
      sleep apnea, patients with an apnea-hypopnea index of 10 or higher had an odds
      ratio of 6.3 (95 percent confidence interval, 2.4 to 16.2) for having a traffic
      accident. This relation remained significant after adjustment for potential
      confounders, such as alcohol consumption, visual-refraction disorders, body-mass
      index, years of driving, age, history with respect to traffic accidents, use of
      medications causing drowsiness, and sleep schedule. Among subjects with an apnea
      hypopnea index of 10 or more, the risk of an accident was higher among those who
      had consumed alcohol on the day of the accident than among those who had not.
      CONCLUSIONS: There is a strong association between sleep apnea, as measured by
      the apnea-hypopnea index, and the risk of traffic accidents.

PMID- 10080848
TI  - Impaired counterregulation of glucose in a patient with hypothalamic sarcoidosis.

PMID- 10080849
TI  - Images in clinical medicine. Right-to-left shunt on a lung scan.

PMID- 10080850
TI  - Carcinoid tumors.

PMID- 10080851
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 8-1999. A 28-year-old man with gram-negative sepsis of uncertain
      cause.

PMID- 10080852
TI  - Heartburn--a serious symptom.

PMID- 10080853
TI  - New treatment for ethylene glycol poisoning.

PMID- 10080854
TI  - Driving with sleep apnea.

PMID- 10080855
TI  - The U.S. Postal Service and cancer screening--stamps of approval?

PMID- 10080856
TI  - Role of serotonin in the immune system and in neuroimmune interactions.
AB  - Serotonin (5-HT) is one of the most extensively studied neurotransmitters of the
      central nervous system. 5-HT is, however, also present in a variety of peripheral
      tissues including in constituents of the immune system. The function of 5-HT in
      the immune system has received increasing attention since about 1984, but has
      been reviewed only once, in 1985. In recent years, modern techniques of molecular
      biology such as reverse-transcriptase polymerase chain reaction and targeted gene
      disruption have made it possible to study new important aspects of 5-HT in the
      immune system. In the first part of the review, we explore whether 5-HT is
      involved in interactions between the central nervous and immune systems. It
      emerges that 5-HT may mediate interactions of these two systems by four different
      pathways. In the second part, we dissect the functional roles of 5-HT in the
      immune system. We describe the distribution of 5-HT receptors and the 5-HT
      transporter on immune cells and estimate which levels 5-HT may attain in the
      extracellular space in physiological conditions and under pathological
      circumstances such as inflammation, thrombosis, and ischemia. At these 5-HT
      concentrations, four major functions for 5-HT emerge. These include T cell and
      natural killer cell activation, delayed-type hypersensitivity responses,
      production of chemotactic factors, and natural immunity delivered by macrophages.
      Finally, we discuss promising future avenues to further advance knowledge of the
      role of 5-HT in the immune system and in neuroimmune interactions.

PMID- 10080857
TI  - Genetically transmitted cholinergic hyperresponsiveness predisposes to
      experimental asthma.
AB  - The excitatory innervation of the airway smooth muscle is primarily cholinergic
      in nature. However, the potential neural mechanism(s) underlying airway
      hyperresponsiveness, one of the hallmarks of asthma, is not fully understood. In
      this study, cholinergic hyperresponsive Flinders sensitive line (FSL) rats and
      their control counterparts, Flinders resistant line (FRL) rats, were repeatedly
      challenged with different doses of nebulized methacholine (0, 4, 16, 64, and 256
      mg/ml) for 5 min. Airway responsiveness was assessed in spontaneously breathing,
      unrestrained animals by means of whole body plethysmography. Increased airway
      responsiveness of FSL rats was evidenced as a more pronounced increase in Penh
      value (enhanced pause, an index of bronchoconstriction) across different
      concentrations of methacholine. In subsequent experiments, FSL and FRL rats were
      sensitized to ovalbumin and challenged with nebulized antigen. Our results
      indicate that the genetically transmitted cholinergic hyperresponsiveness of the
      FSL rat is paralleled by an increased susceptibility to allergen-induced
      bronchoconstriction and inflammation of the airways. This study provides further
      evidence that neural factors can play an important role in determining airway
      responsiveness and thus may be relevant for the expression of asthma. In
      addition, the FSL rat may be a useful model for studies of airway
      hyperresponsiveness.

PMID- 10080858
TI  - Effect of endogenous cortisol levels on natural killer cell activity in healthy
      humans.
AB  - The aim of this study was to examine the effects of increasing and decreasing
      endogenous cortisol levels on natural killer (NK) cell activity in vivo. Normal
      healthy volunteers participated in the following studies: baseline (n = 27),
      metyrapone challenge test (n = 10), dexamethasone suppression test (n = 10), and
      adrenocorticotropic hormone (ACTH) stimulation test (n = 8). Each subject served
      as his own control for each study. Each subject was tested for NK activity and
      plasma cortisol levels at 9 a.m., just before the challenge drug administration,
      and at 10 a.m., except for the dexamethasone study, in which only the 9 a.m.
      blood was drawn, 10 h after the dexamethasone administration. On the baseline
      study day, a significant decrease in plasma cortisol levels was found from 9 to
      10 a.m. (p <.02) along with a significant increase in NK activity (p <.001). On
      the metyrapone test day, plasma cortisol levels at 10 a.m. were significantly
      reduced (p <.005) as expected, while NK activity at the same time point was not
      affected and was increased to an extent equivalent to the baseline study day. On
      the dexamethasone test day, plasma cortisol concentrations were significantly
      decreased (p <.0001) as compared to the same time point on the baseline day,
      without any significant change in the NK activity. On the ACTH test day, plasma
      cortisol rose significantly at 10 a.m. (p <.02), with no change in NK activity.
      We conclude that plasma cortisol alone has no significant effect on NK activity
      in vivo.

PMID- 10080859
TI  - Cytokine dysregulation associated with exam stress in healthy medical students.
AB  - The mechanisms of stress-related immune alterations have not been fully
      elucidated. Cell-mediated immune responses as well as antibody and certain
      cytokines are reported as being suppressed during times of high stress. However,
      the role of suppression vs dysregulation has not been established in human stress
      models. The effect of exam stress on regulatory cytokines in 16 healthy medical
      students was assessed by measuring type-1 (IFN-gamma) and type-2 (IL-10)
      cytokines from 72-h PHA/PMA-stimulated PBMC 4 weeks before and 48 h after exams.
      Results demonstrated decreased IFN-gamma accompanied by increased IL-10 during
      exam stress that resulted in a decreased IFN-gamma:IL-10 ratio. There was a
      significant correlation between the cytokine response to PHA/PMA and number and
      subjective adjustment to daily hassles. Additionally, students who reported
      greater levels of loneliness also reported greater numbers of and poorer
      subjective adjustment to hassles. The differences were consistent in both males
      and females but did not correlate with AM cortisol levels. Additionally, when
      individuals were grouped into high vs low preexam hassle levels, the type-1/type
      2 shift in the IFN-gamma:IL-10 ratio occurred in the low hassles group only.
      These data suggest that psychologically stressful situations shift type-1/type-2
      cytokine balance toward type-2 and result in an immune dysregulation rather than
      overall immunosuppression. This may partially explain the increased incidence of
      type-2-mediated conditions such as increased viral infections, latent viral
      expression, allergic/asthmatic reactions, and autoimmunity reported during
      periods of high stress.

PMID- 10080860
TI  - The influence of a targeted deletion of the IFNgamma gene on emotional behaviors.
AB  - Evidence suggests that interferon-gamma (IFNgamma) plays an important role in CNS
      function and development. While the paucity of agents that selectively modify
      IFNgamma production or interaction with its receptors makes analyses of its
      potential behavioral relevance difficult, mice with null mutations of the
      IFNgamma gene have been used to investigate the potential role of IFNgamma in
      emotional behaviors. C57Bl/6 (B6) mice with null mutations of the IFNgamma gene
      (IFNgamma (-/-)) showed significantly increased emotionality compared to the wild
      type (IFNgamma (+/+)) B6 mice. This was manifested in performance in the elevated
      plus maze as well as increased defecation scores and decreased locomotor activity
      both in novel environments and following a sonic stimulus. In contrast, the
      general level of emotionality of both IFNgamma (+/+) and (-/-) BALB/c (C) mice
      was substantially greater than that of either of the B6 mouse groups. While C
      IFNgamma (-/-) showed increased immobility in response to novelty, other indices
      of emotionality of C IFNgamma (-/-) mice were not significantly different from
      those of the C IFNgamma (+/+) mice. In summary, the lack of IFNgamma appears to
      contribute to increased emotionality, but the basal behaviors of the parental
      strain (e.g., BALBc) may overshadow the expression of this emotionality. While
      mice with null mutations of the IFNgamma gene may be useful tools for
      investigating the role of IFNgamma in brain function and behavior, the influence
      of the parent strain genome(s) on the behaviors in question must be taken into
      account.

PMID- 10080861
TI  - Acknowledgment 

PMID- 10080863
TI  - Wavelet analysis of neuroelectric waveforms 

PMID- 10080864
TI  - Wavelet analysis of neuroelectric waveforms: a conceptual tutorial.
AB  - This paper presents a nontechnical, conceptually oriented introduction to wavelet
      analysis and its application to neuroelectric waveforms such as the EEG and event
      related potentials (ERP). Wavelet analysis refers to a growing class of signal
      processing techniques and transforms that use wavelets and wavelet packets to
      decompose and manipulate time-varying, nonstationary signals. Neuroelectric
      waveforms fall into this category of signals because they typically have
      frequency content that varies as a function of time and recording site. Wavelet
      techniques can optimize the analysis of such signals by providing excellent joint
      time-frequency resolution. The ability of wavelet analysis to accurately resolve
      neuroelectric waveforms into specific time and frequency components leads to
      several analysis applications. Some of these applications are time-varying
      filtering for denoising single trial ERPs, EEG spike and spindle detection, ERP
      component separation and measurement, hearing-threshold estimation via auditory
      brainstem evoked response measurements, isolation of specific EEG and ERP
      rhythms, scale-specific topographic analysis, and dense-sensor array data
      compression. The present tutorial describes the basic concepts of wavelet
      analysis that underlie these and other applications. In addition, the application
      of a recently developed method of custom designing Meyer wavelets to match the
      waveshapes of particular neuroelectric waveforms is illustrated. Matched wavelets
      are physiologically sensible pattern analyzers for EEG and ERP waveforms and
      their superior performance is illustrated with real data examples.

PMID- 10080865
TI  - A wavelet packet model of evoked potentials.
AB  - The standard methods for decomposition and analysis of evoked potentials are
      bandpass filtering, identification of peak amplitudes and latencies, and
      principal component analysis (PCA). We discuss the limitations of these and other
      approaches and introduce wavelet packet analysis. Then we propose the "single
      channel wavelet packet model," a new approach in which a unique decomposition is
      achieved using prior time-frequency information and differences in the responses
      of the components to changes in experimental conditions. Orthogonal sets of
      wavelet packets allow a parsimonious time-frequency representation of the
      components. The method allows energy in some wavelet packets to be shared among
      two or more components, so the components are not necessarily orthogonal. The
      single-channel wavelet packet model and PCA both require constraints to achieve a
      unique decomposition. In PCA, however, the constraints are defined by
      mathematical convenience and may be unrealistic. In the single-channel wavelet
      packet model, the constraints are based on prior scientific knowledge. We give an
      application of the method to auditory evoked potentials recorded from cats. The
      good frequency resolution of wavelet packets allows us to separate superimposed
      components in these data. Our present approach yields estimates of component
      waveforms and the effects of experiment conditions on the amplitude of the
      components. We discuss future extensions that will provide confidence intervals
      and p values, allow for latency changes, and represent multichannel data.

PMID- 10080866
TI  - Feature extraction of event-related potentials using wavelets: an application to
      human performance monitoring.
AB  - This report describes the development and evaluation of mathematical models for
      predicting human performance from discrete wavelet transforms (DWT) of event
      related potentials (ERP) elicited by task-relevant stimuli. The DWT was compared
      to principal components analysis (PCA) for representation of ERPs in linear
      regression and neural network models developed to predict a composite measure of
      human signal detection performance. Linear regression models based on
      coefficients of the decimated DWT predicted signal detection performance with
      half as many free parameters as comparable models based on PCA scores. In
      addition, the DWT-based models were more resistant to model degradation due to
      over-fitting than PCA-based models. Feed-forward neural networks were trained
      using the backpropagation algorithm to predict signal detection performance based
      on raw ERPs, PCA scores, or high-power coefficients of the DWT. Neural networks
      based on high-power DWT coefficients trained with fewer iterations, generalized
      to new data better, and were more resistant to overfitting than networks based on
      raw ERPs. Networks based on PCA scores did not generalize to new data as well as
      either the DWT network or the raw ERP network. The results show that wavelet
      expansions represent the ERP efficiently and extract behaviorally important
      features for use in linear regression or neural network models of human
      performance. The efficiency of the DWT is discussed in terms of its decorrelation
      and energy compaction properties. In addition, the DWT models provided evidence
      that a pattern of low-frequency activity (1 to 3.5 Hz) occurring at specific
      times and scalp locations is a reliable correlate of human signal detection
      performance.

PMID- 10080867
TI  - Detection of P300 waves in single trials by the wavelet transform (WT).
AB  - The P300 response is conventionally obtained by averaging the responses to the
      task-relevant (target) stimuli of the oddball paradigm. However, it is well known
      that cognitive ERP components show a high variability due to changes of cognitive
      state during an experimental session. With simple tasks such changes may not be
      demonstrable by the conventional method of averaging the sweeps chosen according
      to task-relevance. Therefore, the present work employed a response-based
      classification procedure to choose the trials containing the P300 component from
      the whole set of sweeps of an auditory oddball paradigm. For this purpose, the
      most significant response property reflecting the P300 wave was identified by
      using the wavelet transform (WT). The application of a 5 octave quadratic B
      spline-WT on single sweeps yielded discrete coefficients in each octave with an
      appropriate time resolution for each frequency range. The main feature indicating
      a P300 response was the positivity of the 4th delta (0.5-4 Hz) coefficient (310
      430 ms) after stimulus onset. The average of selected single sweeps from the
      whole set of data according to this criterion yielded more enhanced P300 waves
      compared with the average of the target responses, and the average of the
      remaining sweeps showed a significantly smaller positivity in the P300 latency
      range compared with the average of the non-target responses. The combination of
      sweeps classified according to the task-based and response-based criteria
      differed significantly. This suggests an influence of changes in cognitive state
      on the presence of the P300 wave which cannot be assessed by task performance
      alone.

PMID- 10080868
TI  - Time-frequency analysis of single-sweep event-related potentials by means of fast
      wavelet transform.
AB  - A time-frequency decomposition was applied to the event-related potentials (ERPs)
      elicited in an auditory oddball condition to assess differences in cognitive
      information processing. Analysis in the time domain has revealed that cognitive
      processes are reflected by various ERP components such as N1, P2, N2, P300, and
      late positive complex. However, the heterogeneous nature of these components has
      been strongly emphasized due to simultaneously occurring processes. The wavelet
      transform (WT), which decomposes the signal onto the time-frequency plane, allows
      the time-dependent and frequency-related information in ERPs to be captured and
      precisely measured. A four-octave quadratic B-spline wavelet transform was
      applied to single-sweep ERPs recorded in an auditory oddball paradigm. Frequency
      components in delta, theta, and alpha ranges reflected specific aspects of
      cognitive information processing. Furthermore, the temporal position of these
      components was related to specific cognitive processes.

PMID- 10080869
TI  - Oscillatory brain dynamics, wavelet analysis, and cognition.
AB  - On the basis of a systems theoretical approach it was hypothesized that event
      related potentials (ERPs) are superpositions of stimulus-evoked and time-locked
      EEG rhythms reflecting resonance properties of the brain (Basar, 1980). This
      approach led to frequency analysis of ERPs as a way of analyzing evoked rhythms.
      The present article outlines the basic features of ERP frequency analysis in
      comparison to ERP wavelet analysis, a recently introduced method of time
      frequency analysis. Both methods were used in an investigation of the functional
      correlates of evoked rhythms where auditory and visual ERPs were recorded from
      the cat brain. Intracranial electrodes were located in the primary auditory
      cortex and in the primary visual cortex thus permitting "cross-modality"
      experiments. Responses to adequate stimulation (e.g., visual ERP recorded from
      the visual cortex) were characterized by high amplitude alpha (8-16 Hz) responses
      which were not observed for inadequate stimulation. This result is interpreted as
      a hint at a special role of alpha responses in primary sensory processing. The
      results of frequency analysis and of wavelet analysis were quite similar, with
      possible advantages of wavelet methods for single-trial analysis. The results of
      frequency analysis as performed earlier were thus confirmed by wavelet analysis.
      This supports the view that ERP frequency components correspond to evoked rhythms
      with a distinct biological significance.

PMID- 10080870
TI  - Investigating the contamination of electroencephalograms by facial muscle
      electromyographic activity using matching pursuit.
AB  - It has been widely recognized and previously reported that electrical fields from
      facial muscle electromyographic (EMG) activity can contaminate the
      electroencephalogram (EEG), even when closely spaced, bipolar electrode
      configurations are used (personal observations). We suspected that EEG signals
      evoked in response to pressure changes in the upper airway may include EMG
      contamination subsequent to muscle reflexes triggered by the stimuli. We
      evaluated the potential contamination of the background EEG by voluntary
      activation of a facial muscle by obtaining simultaneous recordings in human
      subjects of the EEG (from Cz-C4) and masseter muscle EMG (from a bipolar surface
      electrode pair) before (quiet) and after voluntary tensing (VTen). Matching
      pursuit analysis permitted identification of different time-frequency patterns
      for each signal during the quiet period because the EMG signal has mostly atoms
      above 30 Hz compared to the EEG signal. However, the EEG showed periods of low
      frequency activity unmatched in the EMG TF pattern below 30 Hz. During the
      tensing, most of the atoms of both the EEG and EMG shifted to the higher
      frequency regions above 100 Hz, making the separation difficult. These results
      further suggest that the matching pursuit method may not separate the background
      EEG from phasic EMG signals, both of which are nonstationary in nature.

PMID- 10080871
TI  - Synchronized cortical potentials and wavelet packets: a potential mechanism for
      perceptual binding and conveying information.
AB  - Temporal synchronization in neuronal assemblies has been linked to the functional
      roles of perceptual binding, sensory-motor integration, attention, and
      information coding. We report new evidence for a common underlying mechanism that
      uses specific temporal patterns of synchronized neuronal activity as a basis for
      conveying information. The temporal patterns of stimulus-related synchronized
      neuronal discharges are structured to closely resemble specific members of the
      Symlet wavelet packet family employed in a computational framework. Together,
      these results suggest that temporal patterns of synchronized activity may act as
      a parallel, distributed code for information through a mechanism computationally
      equivalent to wavelet packet analysis.

PMID- 10080873
TI  - Heterozygous defect in HIV-1 coreceptor CCR5 and chemokine production.
AB  - CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic
      isolates of human immunodeficiency virus 1 (HIV-1). An inactive CCR5 allele with
      a 32-nucleotide deletion (CCR5Delta32) has been described that confers resistance
      to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in
      heterozygotes. We found the allele CCR5Delta32 to be not rare in 399 Swiss blood
      donors with a frequency of 0.080. To assess the influence of defective CCR5 on
      production of its ligands we determined the capacity to produce the chemokines
      macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES in comparison
      with the production of the CXC chemokine IL-8 which does not bind to CCR5.
      Production of chemokines was determined during endotoxin stimulation of whole
      blood samples ex vivo. Both, basal and LPS-induced chemokine production in 32
      blood donors heterozygous for CCR5Delta32 were not significantly different when
      compared with 55 blood donors who were homozygous for the wild type CCR5 allele.

PMID- 10080874
TI  - Chemical synthesis and characterization of chemokine RANTES and its analogues.
AB  - RANTES, a polypeptide of 68 amino acid residues, is a member of the C-C chemokine
      subfamily including other monocyte chemoattractants such as MIP-1alpha, MIP
      1beta, MCP-1, MCP-2 and MCP-3. To provide a chemically defined RANTES in quantity
      suitable for structure-function studies, RANTES and its analogues were
      synthesized, using a modified solid-phase chemistry approach. The fully protected
      RANTES and RANTES(3-68) were assembled by automated solid-phase methodology using
      Fmoc chemistry. Deprotection and cleavage of the resin bound peptides yielded
      crude peptides, which were then folded and further purified by reverse-phase
      HPLC. The chemically synthesized RANTES with its identity and purity established,
      was found to be immunochemically and functionally indistinguishable from the
      recombinant human RANTES. RANTES and its analog, RANTES(3-68), have recently been
      used as the substrate in the study of dipeptidyl peptidase IV (CD26)-mediated
      processing of RANTES and its effect on receptor specificity.

PMID- 10080875
TI  - Involvement of NF-kappaB p50/p65 heterodimer in activation of the human pro
      interleukin-1beta gene at two subregions of the upstream enhancer element.
AB  - A region between-3134 and -2729 bp upstream from the transcription site of the
      human pro-interleukin 1beta (proIL-1beta) gene was identified as an LPS
      responsive enhancer element. In this study, the influence of the sequences
      located between -3134 and -2987 on the transcriptional activity of the proIL
      1beta gene in LPS-stimulated Raw 264.7 cells was examined in detail. The results
      obtained by transient transfection of fos -CAT constructs that contained serial
      5'-deletion mutations showed that the region between -3134 and -3059 appears to
      be required for the induction of transcription by LPS. Gel shift assay studies
      with synthetic oligonucleotides corresponding to partial sequences of the latter
      region and nuclear extracts from stimulated cells revealed specific protein
      binding sites between -3110 and -3090 and between -3079 and -3059. These specific
      bindings were time and LPS dose dependent. The results of supershift analysis
      using specific antibodies against transcription factors suggested that both
      binding complexes contained the NF-kappaB components p50 and p65, and did not
      contain other NF-kappaB proteins (p52, c-Rel, Rel B), AP-1 proteins (c-Fos, C
      Jun), CREB or C/EBPbeta (NF-IL6). Mutation of either of the putative NF-kappaB
      binding sites in the enhancer element decreased the LPS-stimulated
      transcriptional activity. These data indicated that two NF-kappaB-binding sites,
      which are located between -3134 and -3059, are critical for the activation of
      proIL-1beta gene transcription.

PMID- 10080876
TI  - Leukaemia inhibitory factor expression is inhibited by glucocorticoids through
      post-transcriptional mechanisms.
AB  - Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine which is involved in
      the regulation of the immune response and haematopoiesis. The authors
      investigated the regulation of the expression of LIF by glucocorticosteroids
      (GC). Endothelial cells (EC) constitutively produce LIF and this production is
      enhanced by interleukin 1 (IL-1). GC were found to inhibit the basal production
      of LIF by EC and to suppress its IL-1-induced augmentation. Whether
      corticosteroids suppress LIF production by blocking transcription of LIF mRNA, or
      by blocking LIF synthesis at a post-transcriptional level was examined. Northern
      blot hybridization analysis demonstrated that GC act mainly by decreasing the LIF
      mRNA level. In the presence of translation inhibitors a superinduction of LIF
      mRNA was observed. Dexamethasone (DEX) at a concentration of 1 microM was
      responsible for a rapid increase in the degradation rate of LIF mRNA which
      resulted in reducing its level by more than 50% within 2 h, whereas the
      transcription rate of LIF gene was not significantly altered in these conditions.
      These results demonstrated that GC inhibit LIF mRNA expression mainly by
      increasing the turnover rate of the LIF mRNA. The early LIF mRNA destabilizing
      activity of GC was translation dependent as shown by experiments with protein
      translation inhibitors. The results indicate that corticosteroids are inhibitors
      of LIF expression and that this inhibition mainly occurs through post
      transcriptional mechanisms.

PMID- 10080877
TI  - Identification of TNF-alpha binding peptides from a D-amino acid hexapeptide
      library that specifically inhibit TNF-alpha binding to recombinant p55 receptor.
AB  - Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine with
      pleiotropic activity that binds to two transmembrane receptors. Its role in
      mediating the inflammatory response to injury or infection has been well
      documented and it has been shown to be a causative factor in rheumatoid
      arthritis, inflammatory bowel disease and septic shock. Using synthetic peptide
      libraries composed exclusively of D-amino acids, two distinct hexapeptide
      families that block the binding of TNF-alpha to its receptors were identified. In
      the deconvolution of the library, activity increased from submillimolar to the
      low micromolar range with the most active compound having an IC50 of 0.33 microM.
      With the aid of biotinylated constructs of these hexapeptides it was possible to
      demonstrate that their antagonistic effect is due to specific binding to TNF
      alpha and not to its receptor.

PMID- 10080878
TI  - Overexpression of tumour necrosis factor alpha in the brain of transgenic mice
      differentially alters nerve growth factor levels and choline acetyltransferase
      activity.
AB  - Tumour necrosis factor alpha (TNF-alpha) is a pleiotrophic cytokine synthesized
      primarily by macrophages and monocytes, which exerts a variety of biological
      activities during inflammatory responses, immune reactions, and wound healing.
      Within the central nervous system (CNS), the basal levels of TNF-alpha are almost
      undetectable, but increase after neurological insults. Using transgenic mice
      expressing high levels of TNF-alpha in the CNS, we investigated the effect of
      this cytokine on the levels of brain nerve growth factor (NGF), a neurotrophin
      playing a crucial role in the development, maintenance and regeneration of basal
      forebrain cholinergic neurons. The immunoenzymatic assay and in situ
      hybridization revealed that the constitutive expression of NGF decreased in the
      hippocampus, increased in the hypothalamus, while remained unchanged in the
      cortex. Moreover, septal cholinergic neurons which receive trophic support from
      NGF produced in the hippocampus display loss of choline acetyltransferase
      immunoreactivity, suggesting that the reduced availability of NGF may influence
      negatively the synthesis of brain cholinergic neurons. These observations
      indicate that the basal level of brain NGF can be influenced negatively or
      positively by local expression of TNF-alpha and that this cytokine, through dose
      dependent regulation of NGF synthesis and release, may be involved in
      neurodegenerative events associated with aging.

PMID- 10080879
TI  - Human first trimester forebrain cells express genes for inflammatory and anti
      inflammatory cytokines.
AB  - Using in situ hybridization and immunohistochemistry the induction of potential
      cytokines [interleukin 1beta (IL-1beta), IL-4, IL-6, IL-10, tumour necrosis
      factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth
      factor beta (TGF-beta)] in human embryonic forebrain cells at weeks 5, 7 and 10
      of gestation was studied. The aims were to investigate the capacity of these
      cells to express cytokines, to determine the kinetics of induction and to display
      the type of cytokine expressing cells in the developing brain. Constitutive
      cytokine gene expression was recorded from week 5, augmented by about 50% at week
      7 and by more than 100% at week 19 (except TGF-beta at week 10). Among other
      cytokines, IL-1beta exhibited the highest expression at week 10. TGF-beta showed
      maximum expression at week 7 and declined at week 10. Combined techniques
      revealed that glial cells are a major source of cytokines. The study show and
      present for the first time the kinetics of spontaneous cytokine expression in
      human embryonic forebrain cells. The increased mRNA expressions with age suggest
      an important role for cytokines in promotion of brain development. The capacity
      of inducing these cytokines may, however, be implicated in the immunopathogenesis
      of several brain diseases. The distinctive TGF-beta profile suggests a further
      role for TGF-beta on modulation of cytokine responses during development.

PMID- 10080880
TI  - Influence of recombinant human erythropoietin on neutrophil function in premature
      neonates.
AB  - The in vivo influence of recombinant human erythropoietin (rhEpo) and iron on
      human neutrophil (PMN) antimicrobial function was assessed. A total of 21 preterm
      infants were randomized to receive either 200 U/kg/other day of rHuEPO+12
      mg/kg/day of iron (EPO+high Fe, seven infants) or 200 U/kg/other day of rhEPO+4
      mg/kg/day of iron (EPO+standard Fe, 9 infants) or 4 mg/kg/day of iron only
      (standard Fe, five infants). PMNs were isolated from blood of these infants 60+/
      5 days after birth and from eight healthy adults. No differences between infants
      and adults were found in PMN random migration and chemotactic activity to N
      formylmethionyl leucyl phenylalanine (FMLP), superoxide anion production in
      response to FMLP and phagocytosis of Staphylococcus aureus. In contrast,
      percentage phagocytosis was significantly lower in EPO+standard Fe as compared to
      both EPO+high Fe and standard Fe groups (P<0.01). This modest impairment of
      phagocytic activity of neonatal PMNs found in association with administration of
      rhEPO and standard iron may be related to consumption of iron during rhEPO
      enhanced erythropoiesis.

PMID- 10080881
TI  - Cytokine release from placental endothelial cells, a process associated with
      preterm labour in the absence of intrauterine infection.
AB  - There is currently a great deal of interest in the role that cytokines may play
      in the processes mediating preterm as well as normal term labour. In case of
      preterm delivery a cause-effect relationship between infection, uncontrollable
      preterm labour, and increased uterine cytokine concentrations is widely accepted,
      but there is considerable information that increased uterine cytokine release is
      also a condition in normal term labour and preterm labour not due to infection.
      Thereby, the exact cellular sources of cytokine production have not yet been
      identified. In the present study, the authors used immunohistochemical analysis
      to localize interleukin 1beta (IL-1beta) interleukin 6 (IL-6) and tumour necrosis
      factor alpha (TNF-alpha) immunoreactivity within trophoblastic villi and fetal
      membranes. In the absence of chorioamnionitis, uncontrollable preterm labour, and
      also normal term labour was associated with strong immunoreactivity for IL-1beta
      and IL-6 in the endothelial cells within trophoblastic villi. In contrast,
      preterm delivery accompanied by histologically confirmed chorioamnionitis, was
      not associated with increased expression of cytokine antigens within endothelial
      cells of the fetal vascular system, but strong cytokine activity was found in
      polymorphonuclear cells infiltrating the amniochorionic membranes. Therefore, the
      data suggest two well-defined subgroups among patients delivering preterm.
      Thereby, increased uterine cytokine concentrations may be realized in both
      groups, but the cellular sources of cytokine production may be different.

PMID- 10080882
TI  - Interleukin 10 production in patients undergoing cardiopulmonary bypass: evidence
      of inhibition of Th-1-type responses.
AB  - The cardiopulmonary bypass (CPB) procedure has long been associated with a
      generalized immunosuppression. To understand further the cytokine-mediated
      regulation of the complex physiological and immunological changes induced by CPB,
      the authors decided to investigate whether CPB affects the release of interleukin
      (IL)-10, as well as other cytokines, in correlation to the inhibition of T cell
      responses. Using phytohaemagglutinin (PHA) as mitogen and peripheral blood
      mononuclear cells (PBMC) isolated from patients undergoing CPB, we investigated
      whether this procedure has an effect on the secretion of different patterns of
      cytokines (Th1- and Th2-type) and PBMC proliferation. In all patients, CPB
      significantly enhances IL-10 and IL-6 production in resting and PHA-stimulated
      PBMC. On the other hand, IL-2 production, in response to PHA, was significantly
      diminished. Reduced IL-2 and enhanced IL-10 production were associated with a
      significant decrease in PBMC proliferation. Immunosuppression was also associated
      to lymphopenia, while neutrophil counts were significantly enhanced. These
      results show that after CPB there is a transient but clear unbalanced immune
      response demonstrated by a differentiated production of Th1- and Th2-type
      cytokines. The release of different patterns of cytokines observed after CPB may
      be helpful in understanding and preventing the development of infectious and
      immune complications in surgical procedure employing CPB.

PMID- 10080883
TI  - Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status
      as prognostic factors in lung cancer.
AB  - Raised serum levels of interleukin 6 (IL-6) have been described in cancer
      patients. This cytokine mediates the acute phase response and has been also
      involved in the pathogenesis of cancer cachexia. The objectives of the present
      study were: (1) to determine the relationships of IL-6 and other cytokines with
      neoplasia extension, acute phase response and nutritional status, in lung cancer
      patients; and (2) to establish the prognostic value of serum cytokine levels. A
      prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF
      alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly
      diagnosed lung cancer patients. Nutritional status was assessed objectively.
      Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute
      phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were
      determined. Increased IL-6 levels were related to extensive disease, impaired
      performance status, enhanced acute phase response and malnutrition. Raised serum
      IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase
      response and low IFN-gamma were all related to a shorter survival. When assessed
      by a multivariate analysis, IL-6 kept its independent prognostic value together
      with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is
      increased in lung cancer patients, enhances the acute phase response in them, and
      is correlated with poor nutritional status, impaired performance status and
      shorter survival.

PMID- 10080884
TI  - Simultaneous detection of IFN-gamma and IL-4 mRNAs using RT-PCR and time-resolved
      fluorometry.
AB  - Time-resolved fluorometry was applied in the detection of RT-PCR amplified mRNAs
      for the Th1 and Th2 cell-derived cytokines interferon gamma (IFN-gamma) and
      interleukin (IL-)4, respectively. RNA stimulated cells was reverse transcribed
      and the cDNAs for the cytokine mRNAs and the constantly expressed beta-actin
      (beta-ACT) mRNA were simultaneously amplified in one multiplex PCR reaction. The
      PCR conditions were optimized to minimize mutual inhibition of individual
      amplifications. One of the PCR primers in each primer pair was biotinylated, and
      the PCR products were captured onto streptavidin-coated microtitre plates. The
      three PCR products were detected with three different lanthanide labelled target
      specific probes in solution hybridization. IFN-gamma, IL-4 and beta-ACT were
      detected with europium (Eu), terbium (Tb) and samarium (Sm) labelled probes,
      respectively, using time-resolved fluorometry. Small cell numbers used in
      microtitre plate cultures were sufficient to detect cytokine messages after
      mitogen stimulation. This sequence-based method provides a sensitive, specific,
      fast and nonisotopic alternative to conventional blotting and hybridisation with
      radioactive probes. In addition, the multiplex fluorogenic dye detection
      facilitates relative quantification of target mRNAs.

PMID- 10080885
TI  - Structure of a binary complex of HhaI methyltransferase with S-adenosyl-L
      methionine formed in the presence of a short non-specific DNA oligonucleotide.
AB  - We have determined a structure for a complex formed between HhaI
      methyltransferase (M.HhaI) and S-adenosyl-L-methionine (AdoMet) in the presence
      of a non-specific short oligonucleotide. M.HhaI binds to the non-specific short
      oligonucleotides in solution. Although no DNA is incorporated in the crystal,
      AdoMet binds in a primed orientation, identical with that observed in the ternary
      complex of the enzyme, cognate DNA, and AdoMet or S-adenosyl-L-homocysteine
      (AdoHcy). This orientation differs from the previously observed unprimed
      orientation in the M.HhaI-AdoMet binary complex, where the S+-CH3 unit of AdoMet
      is protected by a favorable cation-pi interaction with Trp41. The structure
      suggests that the presence of DNA can guide AdoMet into the primed orientation.
      These results shed new light on the proposed ordered mechanism of binding and
      explains the stable association between AdoMet and M.HhaI.

PMID- 10080886
TI  - The structure and function of the 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase from Haemophilus influenzae.
AB  - The gene encoding the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase of
      Haemophilus influenzae has been cloned and expressed in Escherichia coli. A
      complex of the purified protein with a substrate analog has been crystallized and
      its structure solved by multiple anomalous dispersion using phase information
      obtained from a single crystal of selenomethione-labeled protein. The enzyme
      folds into a four-stranded antiparallel beta-sheet flanked on one side by two
      alpha-helices and on the other by three consecutive alpha-helices, giving a novel
      beta1alpha1beta2beta3alpha2beta4alpha3alpha4alpha5 polypeptide topology. The
      three-dimensional structure of a binary complex has been refined at 2.1 A
      resolution. The location of the substrate analog and a sulfate ion gives
      important insight into the molecular mechanism of the enzyme.

PMID- 10080887
TI  - Structure and interactions with RNA of the N-terminal UUAG-specific RNA-binding
      domain of hnRNP D0.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) D0 has two ribonucleoprotein
      (RNP)-type RNA-binding domains (RBDs), each of which can bind solely to the UUAG
      sequence specifically. The structure of the N-terminal RBD (RBD1) determined by
      NMR is presented here. It folds into a compact alphabeta structure comprising a
      four-stranded antiparallel beta-sheet packed against two alpha-helices, which is
      characteristic of the RNP-type RBDs. Special structural features of RBD1 include
      N-capping boxes for both alpha-helices, a beta-bulge in the second beta-strand,
      and an additional short antiparallel beta-sheet coupled with a beta-turn-like
      structure in a loop. Two hydrogen bonds which restrict the positions of loops
      were identified. Backbone resonance assignments for RBD1 complexed with r(UUAGGG)
      revealed that the overall folding is maintained in the complex. The candidate
      residues involved in the interactions with RNA were identified by chemical shift
      perturbation analysis. They are located in the central and peripheral regions of
      the RNA-binding surface composed of the four-stranded beta-sheet, loops, and the
      C-terminal region. It is suggested that non-specific interactions with RNA are
      performed by the residues in the central region of the RNA-binding surface, while
      specific interactions are performed by those in the peripheral regions. It was
      also found that RBD1 has the ability to inhibit the formation of the quadruplex
      structure.

PMID- 10080888
TI  - Alignment of the two domains of the hairpin ribozyme-substrate complex defined by
      interdomain photoaffinity crosslinking.
AB  - The hairpin ribozyme-substrate complex contains two independently folding domains
      that interact with one another to form a catalytic complex. However, little is
      known about the key structural elements involved in these tertiary interactions.
      Here, we report the use of a photochemical crosslinking method to investigate the
      relative proximity and orientation of the two domains of the hairpin ribozyme.
      This method allows the incorporation of a photochemical azidophenacyl group at
      specified positions within synthetic oligoribonucleotides. Photocrosslinking was
      performed following the assembly of four RNA oligonucleotides into active
      ribozyme-substrate complexes. Two photoagent attachment sites in the substrate
      binding strand within domain A (between positions A7-G8 and A10-G11) and three in
      the 5' strand of domain B (A20-G21, A22-A23 and A24-C25) were studied. Several
      crosslinks between the substrate binding strand and the 5' segment of domain B
      were detected. All of the photo agent-specific crosslinked species were dependent
      upon proper assembly and folding of the ribozyme-substrate complex. In addition,
      a substrate base mutation (G+1 to A+1) that prevents the docking of the two
      domains, blocks the crosslink formation. Four interdomain crosslinks (A7-G8/C25
      A26 (two species); A10-G11/A22 and A24-C25/C12-G13) have been shown to retain
      catalytic activity. Taken together, these results indicate that the characterized
      crosslinks provide important information concerning the alignment of the two
      domains and accurately reflect the active docked conformation of the molecule.

PMID- 10080889
TI  - Analysis of heparin, alpha-dystroglycan and sulfatide binding to the G domain of
      the laminin alpha1 chain by site-directed mutagenesis.
AB  - The 395-residue proteolytic fragment E3, which comprises the two most C-terminal
      LG modules of the mouse laminin alpha1 chain, was previously shown to contain
      major binding sites for heparin, alpha-dystroglycan and sulfatides. The same
      fragment (alpha1LG4-5) and its individual alpha1LG4 and alpha1LG5 modules have
      now been obtained by recombinant production in mammalian cells. These fragments
      were apparently folded into a native form, as shown by circular dichroism,
      electron microscopy and immunological assays. Fragment alpha1LG4-5 bound about
      five- to tenfold better to heparin, alpha-dystroglycan and sulfatides than E3.
      These binding activities could be exclusively localized to the alpha1LG4 module.
      Side-chain modifications and proteolysis demonstrated that Lys and Arg residues
      in the C-terminal region of alpha1LG4 are essential for heparin binding. This was
      confirmed by 14 single to triple point mutations, which identified three non
      contiguous basic regions (positions 2766-2770, 2791-2793, 2819-2820) as
      contributing to both heparin and sulfatide binding. Two of these regions were
      also recognized by monoclonal antibodies which have previously been shown to
      inhibit heparin binding. The same three regions and a few additional basic
      residues also make major contributions to the binding of the cellular receptor
      alpha-dystroglycan, indicating a larger binding epitope. The data are also
      consistent with previous findings that heparin competes for alpha-dystroglycan
      binding.

PMID- 10080890
TI  - Evolution of differential substrate specificities in Mu class glutathione
      transferases probed by DNA shuffling.
AB  - A library of variant enzymes was created by combined shuffling of the DNA
      encoding the human Mu class glutathione transferases GST M1-1 and GST M2-2. The
      parental GSTs are 84 % sequence identical at the protein level, but their
      specific activities with the substrates aminochrome and 2-cyano-1,3-dimethyl-1
      nitrosoguanidine (cyanoDMNG) differ by more than 100-fold. Aminochrome is of
      particular interest as an oxidation product of dopamine and of possible
      significance in the etiology of Parkinson's disease, and cyanoDMNG is a model for
      genotoxic and potentially carcinogenic nitroso compounds. GST M2-2 has at least
      two orders of magnitude higher catalytic activity with both of the substrates
      than any of the other known GSTs, including GST M1-1. The DNA library of variant
      Mu class GST sequences contained "mosaic" structures composed of alternating
      segments of both parental sequences. All clones contained the 5'-end of a GST M1
      1 clone optimized for high-level expression in Escherichia coli. The remainder of
      the sequences derived from segments of GST M2-2 and GST M1-1 DNA. All of the
      clones analyzed contained between two and seven distinct DNA segments. In
      addition, each clone contained an average of approximately one point mutation.
      None of the library clones analyzed was identical with either of the two parental
      structures. Variant GST sequences were expressed in E. coli, and their enzymatic
      activities with aminochrome, cyanoDMNG, and 1-chloro-2,4-dinitrobenzene (CDNB)
      were determined in bacterial lysates. Such screening of more than 70 clones
      demonstrated a continuous range of activities covering at least two orders of
      magnitude for each of the substrates. For a given clone, the activities with
      aminochrome and cyanoDMNG, in spite of their different chemistries, were clearly
      correlated, whereas no strong correlation was found with CDNB. This functional
      correlation suggests a common structural basis for the enzymatic mechanisms for
      conjugation of aminochrome and denitrosation of cyanoDMNG. From an evolutionary
      perspective, the results show that recombination of segments from homologous
      proteins gives rise to a large proportion of functionally competent proteins with
      a range of activities. The data support the proposal that natural evolution of
      protein functions may involve recombination of DNA segments followed by selection
      for advantageous functional properties of the resulting proteins. Clearly, the
      same approach can be utilized in the engineering of proteins displaying novel
      functions by in vitro evolution.

PMID- 10080891
TI  - A mutation that uncouples allosteric regulation of carbamyl phosphate synthetase
      in Drosophila.
AB  - In animals, UTP feedback inhibition of carbamyl phosphate synthetase II (CPSase)
      controls pyrimidine biosynthesis. Suppressor of black (Su(b) or rSu(b)) mutants
      of Drosophila melanogaster have elevated pyrimidine pools, and this mutation has
      been mapped to the rudimentary locus. We report that rSu(b) is a missense
      mutation resulting in a glutamate to lysine substitution within the second ATP
      binding site (i.e. CPS.B2 domain) of CPSase. This residue corresponds to Glu780
      in the Escherichia coli enzyme (Glu1153 in hamster CAD) and is universally
      conserved among CPSases. When a transgene expressing the Glu-->Lys substitution
      was introduced into Drosophila lines homozygous for the black mutation, the
      resulting flies exhibited the Su(b) phenotype. Partially purified CPSase from
      rSu(b) and transgenic flies carrying this substitution exhibited a dramatic
      reduction in UTP feedback inhibition. The slight UTP inhibition observed with the
      Su(b) enzyme in vitro was due mainly to chelation of Mg2+ by UTP. However, the Km
      values for glutamate, bicarbonate, and ATP obtained from the Su(b) enzyme were
      not significantly different from wild-type values. From these experiments, we
      conclude that this residue plays an essential role in the UTP allosteric
      response, probably in propagating the response between the effector binding site
      and the ATP binding site. This is the first CPSase mutation found to abolish
      feedback inhibition without significantly affecting other enzyme catalytic
      parameters.

PMID- 10080892
TI  - Motor protein decoration of microtubules grown in high salt conditions reveals
      the presence of mixed lattices.
AB  - We have used back-projection methods to obtain three-dimensional maps of motor
      protein decorated nine and ten protofilament microtubules polymerized in the
      presence of high salt and preserved in vitreous ice. The resulting three
      dimensional maps show that the vast majority of these microtubules have multiple
      seams, rather than being helical as would be expected according to the lattice
      accommodation model. These results indicate that microtubules should be analyzed
      by back-projection before using helical reconstruction approaches, and that nine
      and ten protofilament microtubules polymerized in high salt conditions are not
      suitable for helical analysis.

PMID- 10080893
TI  - Morphogenesis of liposomes encapsulating actin depends on the type of actin
      crosslinking.
AB  - To study the morphogenesis of cells caused by the organization of their internal
      cytoskeletal network, we characterized the transformation of liposomes
      encapsulating actin and its crosslinking proteins, fascin, alpha-actinin, or
      filamin, using real-time high-intensity dark-field microscopy. With increasing
      temperature, the encapsulated G-actin polymerized into actin filaments and formed
      bundles or gels, depending on the type of actin-crosslinking protein that was co
      encapsulated, causing various morphological changes of liposomes. The differences
      in morphology among transformed liposomes indicate that actin-crosslinking
      proteins determine liposome shape by organizing their specific actin networks.
      Morphological analysis reveals that the crosslinking manner, i.e. distance and
      angular flexibility between adjacent crosslinked actin filaments, is essential
      for the morphogenesis rather than their binding affinity and stoichiometry to
      actin filaments.

PMID- 10080894
TI  - Stable sheared A.C pair in DNA hairpins.
AB  - Single-residue d(Pu1NPu2) (Pu1.Pu2=G.A, G.G or A.A) hairpin loops can be stably
      closed by sheared purine.purine pairs. These special motifs have been found in
      several important biological systems. We now extend these loop-closing base-pairs
      to a sheared purine. pyrimidine (A.C) pair at a neutral pH condition. High
      resolution NMR spectroscopy, distance geometry, and molecular dynamics methods
      were used to study d(GTACANCGTAC) oligomers. Numerous idiosyncratic nuclear
      Overhauser enhancements, especially those across the A.C base-pair between
      C4NH2left and right arrow AH1', C4NH2left and right arrow AH2, and CH5left and
      right arrow AH2 proton pairs, clearly define the novel sheared nature of the
      closing A.C base-pair. This novel base-pair is possibly present in several
      biological systems and in two single-stranded DNA aptamers selected from
      oligonucleotide libraries.

PMID- 10080895
TI  - Structure, backbone dynamics and interactions with RNA of the C-terminal RNA
      binding domain of a mouse neural RNA-binding protein, Musashi1.
AB  - Musashi1 is an RNA-binding protein abundantly expressed in the developing mouse
      central nervous system. Its restricted expression in neural precursor cells
      suggests that it is involved in the regulation of asymmetric cell division.
      Musashi1 contains two ribonucleoprotein (RNP)-type RNA-binding domains (RBDs),
      RBD1 and RBD2. Our previous studies showed that RBD1 alone binds to RNA, while
      the binding of RBD2 is not detected under the same conditions. Joining of RBD2 to
      RBD1, however, increases the affinity to greater than that of RBD1 alone,
      indicating that RBD2 contributes to RNA-binding. We have determined the three
      dimensional solution structure of the C-terminal RBD (RBD2) of Musashi1 by NMR.
      It folds into a compact alpha beta structure comprising a four-stranded
      antiparallel beta-sheet packed against two alpha-helices, which is characteristic
      of RNP-type RBDs. Special structural features of RBD2 include a beta-bulge in
      beta2 and a shallow twist of the beta-sheet. The smaller 1H-15N nuclear
      Overhauser enhancement values for the residues of loop 3 between beta2 and beta3
      suggest that this loop is flexible in the time-scale of nano- to picosecond
      order. The smaller 15N T2 values for the residues around the border between
      alpha2 and the following loop (loop 5) suggest this region undergoes
      conformational exchange in the milli- to microsecond time-scale. Chemical shift
      perturbation analysis indicated that RBD2 binds to an RNA oligomer obtained by in
      vitro selection under the conditions for NMR measurements, and thus the nature of
      the weak RNA-binding of RBD2 was successfully characterized by NMR, which is
      otherwise difficult to assess. Mainly the residues of the surface composed of the
      four-stranded beta-sheet, loops and C-terminal region are involved in the
      interaction. The appearance of side-chain NH proton resonances of arginine
      residues of loop 3 and imino proton resonances of RNA bases upon complex
      formation suggests the formation of intermolecular hydrogen bonds. The structural
      arrangement of the rings of the conserved aromatic residues of beta2 and beta3 is
      suitable for stacking interaction with RNA bases, known to be one of the major
      protein-RNA interactions, but a survey of the perturbation data suggested that
      the stacking interaction is not ideally achieved in the complex, which may be
      related to the weaker RNA-binding of RBD2.

PMID- 10080896
TI  - Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase
      inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase.
AB  - Uracil-DNA glycosylase (UDG), which is a critical enzyme in DNA base-excision
      repair that recognizes and removes uracil from DNA, is specifically and
      irreversably inhibited by the thermostable uracil-DNA glycosylase inhibitor
      protein (Ugi). A paradox for the highly specific Ugi inhibition of UDG is how Ugi
      can successfully mimic DNA backbone interactions for UDG without resulting in
      significant cross-reactivity with numerous other enzymes that possess DNA
      backbone binding affinity. High-resolution X-ray crystal structures of Ugi both
      free and in complex with wild-type and the functionally defective His187Asp
      mutant Escherichia coli UDGs reveal the detailed molecular basis for duplex DNA
      backbone mimicry by Ugi. The overall shape and charge distribution of Ugi most
      closely resembles a midpoint in a trajectory between B-form DNA and the kinked
      DNA observed in UDG:DNA product complexes. Thus, Ugi targets the mechanism of
      uracil flipping by UDG and appears to be a transition-state mimic for UDG
      flipping of uracil nucleotides from DNA. Essentially all the exquisite shape,
      electrostatic and hydrophobic complementarity for the high-affinity UDG-Ugi
      interaction is pre-existing, except for a key flip of the Ugi Gln19 carbonyl
      group and Glu20 side-chain, which is triggered by the formation of the complex.
      Conformational changes between unbound Ugi and Ugi complexed with UDG involve the
      beta-zipper structural motif, which we have named for the reversible pairing
      observed between intramolecular beta-strands. A similar beta-zipper is observed
      in the conversion between the open and closed forms of UDG. The combination of
      extremely high levels of pre-existing structural complementarity to DNA binding
      features specific to UDG with key local conformational changes in Ugi resolves
      the UDG-Ugi paradox and suggests a potentially general structural solution to the
      formation of very high affinity DNA enzyme-inhibitor complexes that avoid cross-
      reactivity.

PMID- 10080897
TI  - Crystallographic evaluation of internal motion of human alpha-lactalbumin refined
      by full-matrix least-squares method.
AB  - The low temperature form of human alpha-lactalbumin (HAL) was crystallized from a
      2H2O solution and its structure was refined to the R value of 0.119 at 1.15 A
      resolution by the full-matrix least-squares method. Average estimated standard
      deviations of atomic parameters for non-hydrogen atoms were 0.038 A for
      coordinates and 0.044 A2 for anisotropic temperature factors (Uij). The magnitude
      of equivalent isotropic temperature factors (Ueqv) was highly correlated with the
      distance from the molecular centroid and fitted to a quadratic equation as a
      function of atomic coordinates. The atomic thermal motion was rather isotropic in
      the core region and the anisotropy increased towards the molecular surface. The
      statistical analysis revealed the out-of-plane motion of main-chain oxygen atoms,
      indicating that peptide groups are in rotational vibration around a Calpha.Calpha
      axis. The TLS model, which describes the rigid-body motion in terms of
      translation, libration, and screw motions, was adopted for the evaluation of the
      molecular motion and the TLS parameters were determined by the least-squares fit
      to Uij. The reproduced Ueqvcal from the TLS parameters was in fair agreement with
      observed Ueqv, but differences were found in regions of residues, 5-22, 44-48, 70
      75, and 121-123, where Ueqv was larger than Ueqvcal because of large local
      motions. To evaluate the internal motion of HAL, the contribution of the rigid
      body motion was determined to be 42.4 % of Ueqv in magnitude, which was the
      highest estimation to satisfy the condition that the Uijint tensors of the
      internal motion have positive eigen values. The internal motion represented with
      atomic thermal ellipsoids clearly showed local motions different from those
      observed in chicken-type lysozymes which have a backbone structure very similar
      to HAL. The result indicates that the internal motion is closely related to
      biological function of proteins.

PMID- 10080898
TI  - Solution structure of toxin 2 from centruroides noxius Hoffmann, a beta-scorpion
      neurotoxin acting on sodium channels.
AB  - We have determined the solution structure of Cn2, a beta-toxin extracted from the
      venom of the New World scorpion Centruroides noxius Hoffmann. Cn2 belongs to the
      family of scorpion toxins that affect the sodium channel activity, and is very
      toxic to mammals (LD50=0.4 microg/20 g mouse mass). The three-dimensional
      structure was determined using 1H-1H two-dimensional NMR spectroscopy, torsion
      angle dynamics, and restrained energy minimization. The final set of 15
      structures was calculated from 876 experimental distance constraints and 58 angle
      constraints. The structures have a global r. m.s.d. of 1.38 A for backbone atoms
      and 2.21 A for all heavy atoms. The overall fold is similar to that found in the
      other scorpion toxins acting on sodium channels. It is made of a triple-stranded
      antiparallel beta-sheet and an alpha-helix, and is stabilized by four disulfide
      bridges. A cis-proline residue at position 59 induces a kink of the polypeptide
      chain in the C-terminal region. The hydrophobic core of the protein is made up of
      residues L5, V6, L51, A55, and by the eight cysteine residues. A hydrophobic
      patch is defined by the aromatic residues Y4, Y40, Y42, W47 and by V57 on the
      side of the beta-sheet facing the solvent. A positively charged patch is formed
      by K8 and K63 on one edge of the molecule in the C-terminal region. Another
      positively charged spot is represented by the highly exposed K35. The structure
      of Cn2 is compared with those of other scorpion toxins acting on sodium channels,
      in particular Aah II and CsE-v3. This is the first structural report of an anti
      mammal beta-scorpion toxin and it provides the necessary information for the
      design of recombinant mutants that can be used to probe structure-function
      relationships in scorpion toxins affecting sodium channel activity.

PMID- 10080899
TI  - Crystal structure of a protein with an artificial exon-shuffling, module M4
      substituted chimera hemoglobin beta alpha, at 2.5 A resolution.
AB  - The crystal structure of the homotetramer of a chimera beta alpha-subunit of
      human hemoglobin was refined at 2.5 A resolution. The chimera subunit was
      constructed by replacing an exon-encoded module M4 of the beta-subunit with that
      of the alpha-subunit, simulating an exon-shuffling event. The implanted module M4
      retained the native alpha-subunit structure, while module M3 was disturbed around
      the site where a new type of intron was recently found. Some of the residues were
      found in alternative conformations that avoid steric hindrance at the subunit
      interface. The modules are modestly rigid in their backbone structures by using
      side-chains to compensate for interface incompatibility.

PMID- 10080900
TI  - The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate
      aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism
      and specificity.
AB  - The structure of a class II fructose-1,6-bisphosphate aldolase in complex with
      the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH) has been
      determined using X-ray diffraction terms to a resolution of 2.0 A (1 A=0.1 nm).
      The crystals are trigonal, space group P3121 with a=b=78.24 A, c=289.69 A. The
      asymmetric unit is a homodimer of (alpha/beta)8 barrels and the model has refined
      to give R-work 19.2 %, R-free (based on 5 % of the data) 23.0 %. PGH resembles
      the ene-diolate transition state of the physiological substrate dihydroxyacetone
      phosphate. It is well ordered and bound in a deep polar cavity at the C-terminal
      end of the (alpha/beta)8 barrel, where it chelates the catalytic zinc ion using
      hydroxyl and enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc
      ion is completed by three histidine residues. The complex network of hydrogen
      bonds at the catalytic centre is required to organise the position of key
      functional groups and metal ion ligands. A well-defined monovalent cation-binding
      site is observed following significant re-organisation of loop structures. This
      assists the formation of a phosphate-binding site on one side of the barrel that
      tethers PGH in the catalytic site. The positions of functional groups of
      substrate and putative interactions with key amino acid residues are identified.
      Knowledge of the complex structure complements the results of spectroscopic and
      site-directed mutagenesis studies, and contributes to our understanding of the
      mechanism and substrate specificity of this family of enzymes. A reaction
      mechanism distinct from that proposed for other class II aldolases is discussed.
      The results suggest that the class II aldolases should be sub-divided into two
      groups on the basis of both distinct folds and mechanism.

PMID- 10080901
TI  - Conformational analysis of a set of peptides corresponding to the entire primary
      sequence of the N-terminal domain of the ribosomal protein L9: evidence for
      stable native-like secondary structure in the unfolded state.
AB  - There is considerable interest in the structure of the denatured state and in the
      role local interactions play in protein stability and protein folding. Studies of
      peptide fragments provide one method to assess local conformational preferences
      which may be present in the denatured state under native-like conditions. A set
      of peptides corresponding to the individual elements of secondary structure
      derived from the N-terminal domain of the ribosomal protein L9 have been
      synthesized. This small 56 residue protein adopts a mixed alpha-beta topology and
      has been shown to fold rapidly in an apparent two-state fashion. The
      conformational preferences of each peptide have been analyzed by proton nuclear
      magnetic resonance spectroscopy and circular dichroism spectroscopy. Peptides
      corresponding to each of the three beta-stands and to the first alpha-helix are
      unstructured as judged by CD and NMR. In contrast, a peptide corresponding to the
      C-terminal helix is remarkably structured. This 17 residue peptide is 53 %
      helical at pH 5.4, 4 degrees C. Two-dimensional NMR studies demonstrate that the
      helical structure is distributed approximately uniformly throughout the peptide,
      although there is some evidence for fraying at the C terminus. Detailed analysis
      of the NMR spectra indicate that the helix is stabilized, in part, by a native N
      capping interaction involving Thr40. A mutant peptide which lacks Thr40 is only
      32 % helical. pH and ionic strength-dependent studies suggested that charge
      charge interactions make only a modest net contribution to the stability of the
      peptide. The protein contains a trans proline peptide bond located at the first
      position of the C-terminal helix. NMR analysis of the helical peptide and of a
      smaller peptide containing the proline residue indicates that only a small amount
      of cis proline isomer (8 %) is likely to be populated in the unfolded state.

PMID- 10080902
TI  - Predicting the rate enhancement of protein complex formation from the
      electrostatic energy of interaction.
AB  - The rate of association of proteins is dictated by diffusion, but can be enhanced
      by favorable electrostatic forces. Here the relationship between the
      electrostatic energy of interaction, and the kinetics of protein-complex
      formation was analyzed for the protein pairs of: hirudin-thrombin,
      acetylcholinesterase-fasciculin and barnase-barstar, and for a panel of point
      mutants of these proteins. Electrostatic energies of interaction were calculated
      as the difference between the electrostatic energy of the complex and the sum of
      the energies of the two individual proteins, using the computer simulation
      package DelPhi. Calculated electrostatic energies of interaction were compared to
      experimentally determined rates of association. One kcal/mol of Coulombic
      interaction energy increased the rate of association by a factor of 2.8,
      independent of the protein-complex or mutant analyzed. Electrostatic energies of
      interaction were also determined from the salt dependence of the association rate
      constant, using the same basic equation as for the theoretical calculation. A
      Bronsted analysis of the electrostatic energies of interactions plotted versus
      experimentally determined ln(rate)s of association shows a linear relation
      between the two, with a beta value close to 1. This is interpreted as the energy
      of the transition state varies according to the electrostatic interaction energy,
      fitting a two state model for the association reaction. Calculating electrostatic
      rate enhancement from the electrostatic interaction energy can be used as a
      powerful tool to design protein complexes with altered rates of association and
      affinities.

PMID- 10080903
TI  - Acquisition of native-like interactions in C-terminal fragments of barnase.
AB  - We have characterised a series of C-terminal fragments of barnase by different
      biophysical techniques to find out when they acquire secondary and tertiary
      native-like structure. Fragments B96-110 (which comprises the last 15 residues of
      the intact protein) up to B37-110 (which involves most of the protein except the
      two first helices and a loop) were mainly disordered. Only fragment B23-110,
      which lacks alpha-helix1, showed native-like near and far-UV CD and fluorescence
      spectra. The intensities of these spectra were lower than those of the full
      length protein, which suggests the absence of complete side-chain packing. Urea
      denaturation followed by fluorescence, far-UV CD and gel-filtration
      chromatography techniques indicated a co-operative transition only for B23-110.
      None of the fragments melted co-operatively with temperature. Thus, the formation
      of secondary and tertiary structure requires most of the polypeptide chain to be
      present, that is, secondary and tertiary structure are formed in parallel. This
      agrees with the proposed model for barnase folding, where the residual structure
      in small fragments is weak and flickering, and it is only consolidated when there
      are enough tertiary interactions. Thus, the development of structure in the
      series of C-terminal fragments follows a similar behaviour to that observed in
      the series of N-terminal fragments of barnase.

PMID- 10080905
TI  - Editorial 

PMID- 10080904
TI  - Stability of the residual structure in unfolded BPTI in different conditions of
      temperature and solvent composition measured by disulphide kinetics and double
      mutant cycle analysis.
AB  - The folding funnel model proposes a clear description of the protein folding
      process. To test this model, additional data on the structures populated in
      different stages of folding and their influence on further folding are required.
      Here, we use the double mutant strategy and disulphide formation kinetics
      measurements to study the impact on folding of the residual structure in unfolded
      bovine pancreatic trypsin inhibitor (BPTI). We show how five amino acid residues
      stabilise a folding initiation site, possibly a beta-hairpin, and influence the
      shape of the upper region of the folding funnel in BPTI in different conditions
      of temperature and solvent composition. Our data provide experimental evidence
      for the mechanism by which a fast search for a proper chain topology is made
      possible early in the folding of proteins. The results apply to proteins in
      general, not necessarily just to disulphide bonded proteins, since cysteine
      residues are used here merely as reporter groups.

PMID- 10080906
TI  - Purification of hematopoietic stem cells for further biological study.
AB  - For many years, the hematopoietic system has provided a convenient and
      fascinating model for studies of the molecular processes regulating cell growth
      and differentiation. However, this system also poses considerable challenges
      because the most primitive "stem" cells as well as their initial differentiating
      progeny are normally present in hematopoietic tissues at extremely low
      frequencies and no unique, stable phenotype has yet been identified to allow
      hematopoietic cells with specific stem and progenitor functions to be measured
      directly. Rather, this requires the use of functional assays that detect their
      developmental properties and take several weeks to complete. Accordingly, many
      investigations of primitive hematopoietic cell behavior and their responses to
      molecular cues in the environment have relied on the development of cell
      separation techniques specifically designed for obtaining highly enriched
      populations of primitive hematopoietic cells. Key to these procedures is the use
      of a preenrichment step(s) in which differences in cell density, size, or
      sensitivity to pharmacological agents or surface phenotype are exploited to first
      "debulk" the sample. This step can then be followed by a more selective antibody
      mediated procedure to generate useful numbers of highly purified cells. Batchwise
      immunoadsorption techniques offer many advantages for obtaining enriched
      populations of hematopoietic progenitors because they avoid the nonspecific
      toxicity seen with antibody-mediated cell killing and are suitable for rapidly
      processing large samples. For any cell separation procedure, a balance must be
      struck between the purity and the recovery of the desired cells because steps to
      increase cell purity usually reduce yields. Both the negative and the positive
      selection techniques are useful strategies but negative selection usually
      requires one less manipulation step and circumvents potential effects incurred by
      the presence of antibody on the surface of the cell being isolated. Specific
      details for the use and results obtained with an immunomagnetic negative column
      selection technique are then presented.

PMID- 10080907
TI  - Monitoring antisense oligodeoxynucleotide activity in hematopoietic cells.
AB  - Traditionally, methods designed to impair translation through direct interactions
      with target messenger RNA (mRNA) have been designated as "antisense" strategies
      because of their reliance on the formation of reverse complementary (antisense)
      Watson-Crick base pairs between the targeting oligodeoxynucleotide (ODN) and the
      mRNA whose function is to be disrupted. Proof of putative "antisense effects,"
      and other mechanistic studies, would be greatly facilitated by the ability to
      directly demonstrate hybridization between an antisense (AS) ODN and its mRNA
      target in vivo. In addition, evidence of AS activity by demonstrating reduced
      levels of RNA or protein or by showing cleaved target molecules would lend proof
      of the concept. In this article we discuss how AS ODN may be used to down
      regulate target gene expression with an emphasis on those targets chosen for our
      investigations, and we summarize the methods employed for this type of study.

PMID- 10080908
TI  - Analysis of the modulation of transcriptional activity in myelopoiesis and
      leukemogenesis.
AB  - Acute myeloid leukemia (AML) is still associated with a mortality of 60 to 80%.
      AML is characterized by a block in myeloid differentiation. The transcription
      factors PU.1 and C/EBPalpha are responsible for normal myeloid differentiation
      from stem cells to monocytes or granulocytes. In particular, PU.1 induces
      expression of the macrophage colony-stimulating factor (M-CSF) receptor and the
      development of monocytes, whereas C/EBPalpha increases the expression of the
      granulocyte colony-stimulating factor (G-CSF) receptor and leads to mature
      granulocytes. In AML, chromosomal aberrations result in oncoproteins such as
      AML1/ETO, PML/RARalpha, or activated Ras, which can deregulate genes important
      for normal myelopoiesis. Thus, AML1/ETO can bind to the transcription factor
      C/EBPalpha, inhibit C/EBPalpha-dependent transcription, and block granulocytic
      differentiation. However, AML1/ETO can also synergize with the transcription
      factor AML1 to enhance the activity of the M-CSF receptor promoter. On the other
      hand, the PML/RARalpha fusion protein causes transcriptional repression by
      recruiting the nuclear corepressor (N-CoR) histone deacetylase complex to the
      DNA, which results in decreased histone acetylation and a repressive chromatin
      organization. Here we describe methods to investigate whether and how signaling
      agonists induce myeloid differentiation and how oncoproteins might cause AML by
      modulating the activity of transcription factors that are pivotal for normal
      myeloid development.

PMID- 10080909
TI  - Thrombopoietin signal transduction: studies from cell lines and primary cells.
AB  - Thrombopoietin (TPO) and its receptor Mpl support all of the developmental step
      necessary for megakaryocytopoiesis. In the past few years, the signaling pathways
      utilized by this member of the cytokine receptor family have been extensively
      studied, especially JAK/STAT, Ras/MAP kinase, Shc, and other adapter molecules.
      Many if not most of the secondary signaling pathways activated by thrombopoietin
      have also been identified upon binding of other hematopoietic growth factors to
      their cognate receptors, making the study of Mpl signaling representative of the
      field in general. However, identifying unique molecules or combinations of
      signals that direct megakaryocyte development has been an elusive goal and has
      led some investigators to conclude that there is little specificity during Mpl
      signal transduction. In this article we review the data regarding Mpl signaling
      with particular attention to the methods employed and critical interpretation of
      the data generated. Future studies will have to focus on primary bone marrow
      cells and intact animal models rather than transformed cell lines. Furthermore,
      it is likely that a comprehensive, integrative analysis of the many pathways
      activated by ligand binding will be necessary to understand the physiology of
      cytokine signaling.

PMID- 10080910
TI  - Regulation of megakaryocytopoiesis and platelet production by tyrosine kinases
      and tyrosine phosphatases.
AB  - Megakaryocytopoiesis is the process by which bone marrow progenitor cells develop
      into mature megakaryocytes, which in turn produce platelets required for normal
      hemostasis. The development of this hematopoietic lineage depends on a variety of
      growth factors and cytokines. Growth factor-dependent tyrosine kinase receptors
      important in megakaryocytopoiesis include c-Kit, fibroblast growth factor
      receptor, the RON receptor, and the macrophage colony-stimulating factor
      receptor. Binding of growth factors to their respective receptors results in
      receptor dimerization and subsequent autophosphorylation on tyrosine residues.
      Tyrosine autophosphorylations become sites of association for cytoplasmic
      signaling molecules via their SH2 domains. Some of these molecules are themselves
      cytoplasmic tyrosine kinases such as the Src kinases, TEC, and CHK. Others are
      molecules such as phospholipase C-gamma, phosphoinositol 3-kinase, Shc, GTPase
      activating protein, and the SH2-containing tyrosine phosphatases SHP-1 and SHP-2.
      These molecules generate second messengers, regulate the phosphorylation of other
      downstream molecules, and also regulate the phosphorylation of the receptor
      itself. The different cytoplasmic components activate pathways involved in either
      changes in cell growth or changes in the cytoskeleton that affect maturation of
      the cell. Cytokine receptors also generate signals involved in growth and
      differentiation. Some of these second messengers overlap with those of the
      receptor tyrosine kinases. Others, such as the JAKs/STATs, are involved in
      transcriptional control and are unique to the signaling mediated by cytokine
      receptors. We describe the contribution of these different signals to the
      growth/differentiation processes of megakaryocytes. We also describe the
      contribution of receptor and nonreceptor tyrosine phosphatases to these
      processes. Lastly, we have compiled selected methods related to the study of
      protein phosphorylation in megakaryocytes.

PMID- 10080911
TI  - Isolation of differentially expressed genes by cloning transcriptionally active
      DNA fragments.
AB  - During studies of erythroid cell growth and differentiation induced by
      erythropoietin (Epo), we developed a method that allows the identification and
      isolation of genes based upon their transcriptional activity. Transcriptionally
      active genomic DNA fragments from Epo-treated cells and control cells are
      purified from inactive chromatin using mercury affinity chromatography, based on
      the mechanism that the thiol groups of histone H3 on transcriptionally active
      chromatin are exposed to the solvent and therefore are easily accessible. Using
      the purified genomic DNA fragments from the two populations of cells, a
      subtractive hybridization strategy is used to isolate and clone genes that are
      differentially expressed in the absence or in the presence of Epo.

PMID- 10080912
TI  - Cultural Values in Intergroup and Single-Group Social Dilemmas.
AB  - Do cultural values influence the manner in which people cooperate with one
      another? This study assessed cultural characteristics of individuals and then
      related these characteristics to cooperative behavior in social dilemmas.
      Participants were assessed for their degree of vertical and horizontal
      individualism and collectivism, cultural values identified by Triandis (1995).
      They made choices in either a single-group or an intergroup social dilemma. The
      single-group dilemma entailed a three-person dilemma; the intergroup dilemma was
      identical but added subgroup competition, i.e., an opposing three-person group.
      The results indicated an interaction between cultural characteristics and type of
      dilemma for cooperation. The single-group versus intergroup effect reported by
      Bornstein and Ben-Yossef (1994) was replicated, but only for vertical
      individualists. The vertical individualists were least cooperative in the single
      group dilemma but were more cooperative in the intergroup dilemma-where
      cooperation with the group maximized personal outcomes. The vertical
      collectivists were most cooperative in the single-group dilemma but were less
      cooperative in the intergroup dilemma- where group defection resulted in maximum
      group outcomes. The horizontal individualists and collectivists exhibited an
      intermediate level of cooperation, with no differences in cooperation between the
      single-group and intergroup dilemmas. Taken together, the results suggest that
      the relationship between cultural values and cooperation, in particular with
      reference to vertical and horizontal components of individualism and
      collectivism, is more complex than has been suggested in past research. Copyright
      1999 Academic Press.

PMID- 10080913
TI  - Choice-Process Satisfaction: The Influence of Attribute Alignability and Option
      Limitation.
AB  - This research investigates how choice-process satisfaction is influenced by
      limitation of choice option and by the types of features used to represent the
      options. Studies of choice satisfaction have focused on how satisfied the
      decision maker feels about the choice that has been made and have overlooked the
      importance of the process through which the decision maker makes a choice, i.e.,
      choice-process satisfaction. We show that the comparability of choice options
      through alignable features increases choice-process satisfaction, whereas option
      limitation (i.e., making one option unavailable from a set of equally attractive
      options) decreases choice-process satisfaction. Further, this decrease in
      satisfaction, relative to all options being available, occurs for people who are
      given a set of options in which the difference features are alignable (i.e.,
      differences of a corresponding dimension) but not for people who are given a set
      of options in which the difference features are nonalignable (i.e., differences
      of unique dimensions). We propose that alignable differences are easier to
      compare and have more weight in people's attribute processing, and thus give rise
      to a perception of a greater amount of information about the option set that is
      relevant for choice. Making an option unavailable in this case would have a
      bigger impact than in a situation in which all options have nonalignable
      differences. Nonalignable differences are difficult to process and are less
      likely to make people aware that there is very much information about the options
      for decision making. This explanation and the interaction effect between option
      limitation and feature alignability are tested in four experiments. Copyright
      1999 Academic Press.

PMID- 10080914
TI  - Antecedents of Leader Utilization of Staff Input in Decision-Making Teams.
AB  - The purpose of this experiment was to explore the possibility that the
      inconsistent findings of Brehmer and Hagafors (1986, Organizational Behavior and
      Human Decision Processes, 38, 181-195), Sniezek and Buckley (1995, Organizational
      Behavior and Human Decision Processes, 62, 159-174), and leader-member exchange
      research regarding leaders' propensity to differentially and accurately weight
      staff input can be explained as a result of experience, the availability to the
      leader of staff member judgment confidence, and the cumulative past accuracy of
      each staff member. The availability to the team leader of staff member past
      judgment accuracy and staff member judgment confidence was provided in an
      environment in which differential staff weighting was the appropriate staff
      utilization strategy. Eighty-four leaders of four-person decision-making teams
      performed 63 decisions on a computerized decision-making task. Both experience
      and providing leaders with cumulative staff past accuracy information were
      related to greater staff weighting variability and greater staff weighting
      accuracy. Although positively related to staff weighting, staff confidence
      information did not improve leader weighting variability nor actual staff
      weighting accuracy. Copyright 1999 Academic Press.

PMID- 10080915
TI  - A novel endopeptidase with a strict specificity for threonine residues at the P1'
      position.
AB  - An endopeptidase was purified from Archachatina ventricosa by chromatography on
      columns of gel filtration, DEAE-Sepharose and phenyl-Sepharose. The preparation
      was shown to be homogeneous by polyacrylamide gel electrophoresis and capillary
      electrophoresis. The purified enzyme displayed two protein bands on SDS
      polyacrylamide gel electrophoresis with estimated molecular weights of 90,000 and
      121,000. The protease exhibited maximum proteolytic activity at 55 degrees C and
      at pH 8.0, but it retained more than 85% of its activity in the pH range 7.5 to
      8.5. It was completely inactivated by the chelating agents EDTA and 1,10
      phenanthroline which are metalloprotease inhibitors. Studies on substrate
      specificity showed that only the amide bonds of peptide substrates having a
      threonine residue at the P1' position were hydrolyzed by the purified protease.
      This endopeptidase constitutes a novel tool for the study of proteins in view of
      its narrow and unique substrate specificity.

PMID- 10080916
TI  - Cloning and characterization of the L15 ribosomal protein gene homologue from the
      crayfish Orconectes limosus.
AB  - A cDNA homologue of the large unit rat ribosomal protein L15 was cloned from an
      epidermal cDNA library of the crayfish Orconectes limosus, being the first
      crustacean ribosomal protein gene cloned to date. It contains 204 amino acids,
      deduced from the nucleotide sequence, and reveals 70-76% sequence identity with
      other arthropod and vertebrate ribosomal L15s. A single, abundant 0.7-kb mRNA
      transcript was constitutively expressed and revealed similar expression levels,
      among various adult crayfish tissues.

PMID- 10080917
TI  - Characterization of psychrophilic alanine racemase from Bacillus
      psychrosaccharolyticus.
AB  - A psychrophilic alanine racemase gene from Bacillus psychrosaccharolyticus was
      cloned and expressed in Escherichia coli SOLR with a plasmid pYOK3. The gene
      starting with the unusual initiation codon GTG showed higher preference for
      codons ending in A or T. The enzyme purified to homogeneity showed the high
      catalytic activity even at 0 degrees C and was extremely labile over 35 degrees
      C. The enzyme was found to have a markedly large Km value (5.0 microM) for the
      pyridoxal 5'-phosphate (PLP) cofactor in comparison with other reported alanine
      racemases, and was stabilized up to 50 degrees C in the presence of excess
      amounts of PLP. The low affinity of the enzyme for PLP may be related to the
      thermolability, and may be related to the high catalytic activity, initiated by
      the transaldimination reaction, at low temperature. The enzyme has a
      distinguishing hydrophilic region around the residue no. 150 in the deduced amino
      acid sequence (383 residues), whereas the corresponding regions of other Bacillus
      alanine racemases are hydrophobic. The position of the region in the three
      dimensional structure of C atoms of the enzyme was predicted to be in a surface
      loop surrounding the active site. The region may interact with solvent and reduce
      the compactness of the active site.

PMID- 10080918
TI  - A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL,
      regulates osteoclast differentiation and function.
AB  - Osteoclasts, the multinucleated giant cells that resorb bone, develop from
      monocyte-macrophage lineage cells. Osteoblasts or bone marrow stromal cells have
      been suggested to be involved in osteoclastic bone resorption. The recent
      discovery of new members of the tumor necrosis factor (TNF) receptor-ligand
      family has elucidated the precise mechanism by which osteoblasts/stromal cells
      regulate osteoclast differentiation and function. Osteoblasts/stromal cells
      express a new member of the TNF-ligand family "osteoclast differentiation
      factor(ODF)/osteoprotegerin ligand (OPGL)/TNF-related activation-induced cytokine
      (TRANCE)/receptor activator of NF-kB ligand (RANKL)" as a membrane associated
      factor. Osteoclast precursors which possess RANK, a TNF receptor family member,
      recognize ODF/OPGL/TRANCE/RANKL through cell-to-cell interaction with
      osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of
      macrophage colony-stimulating factor. Mature osteoclasts also express RANK, and
      their bone-resorbingactivity is also induced by ODF/OPGL/TRANCE/RANKL which
      osteoblasts/stromal cells possess. Osteoprotegerin (OPG)/osteoclastogenesis
      inhibitory factor (OCIF)/TNF receptor-like molecule 1 (TR1) is a soluble decoy
      receptor for ODF/OPGL/TRANCE/RANKL. Activation of NF-kB and c-Jun N-terminal
      kinase through the RANK-mediated signaling system appears to be involved in
      differentiation and activation of osteoclasts.

PMID- 10080919
TI  - Interaction of S-SCAM with neural plakophilin-related Armadillo-repeat
      protein/delta-catenin.
AB  - Synaptic scaffolding molecule (S-SCAM) is a multiple PDZ domain-containing
      protein, which interacts with neuroligin, a cell adhesion molecule, and the NMDA
      receptor. In this study, we searched for S-SCAM-interacting proteins and obtained
      a neuralplakophilin-related armadillo-repeat protein (NPRAP)/delta-catenin.
      NPRAP/delta-catenin bound to the last PDZ domain of S-SCAM via its carboxyl
      terminus in three different cell-free assay systems, was coimmunoprecipitated
      with S-SCAM from rat crude synaptosomes, and was localized at the excitatory
      synapses in rat hippocampal neurons. NPRAP/delta-catenin may be implicated in the
      molecular organization of synaptic junctions through the interaction with S-SCAM.

PMID- 10080920
TI  - Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal
      transduction pathways in LNCaP prostate cancer cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds modulate various
      endocrine functions by enhancing ligand metabolism, altering hormone synthesis,
      down regulating receptor levels, and interfering with gene transcription. In the
      present study, we investigated the effects of TCDD on testosterone signal
      transduction pathways and vice versa in the androgen receptor (AR) positive LNCaP
      prostate cancer cell line. TCDD induced CYP1A1 mRNA and related enzyme activity
      in these cells, with dose and time-dependence. Both normal and testosterone
      stimulated cell growth was inhibited by TCDD. The expression levels of the aryl
      hydrocarbon receptor (AhR), the aryl hydrocarbon receptor nuclear translocator
      (ARNT), and AR were not affected by exposure to TCDD at a dose of 10 nM for a 24
      hr time period. Testosterone treatment dose-dependently inhibited the TCDD
      induced CYP1A1 mRNA accumulation and related enzyme activity. Reciprocally, TCDD
      also dose-dependently inhibited testosterone-dependent transcriptional activity
      and testosterone-regulated prostate specific antigen (PSA) expression. Taken
      together, these results demonstrate antiandrogenic functions of TCDD and a
      specific ligand-induced bilateral transcriptional interference between TCDD and
      testosterone mediated signal transduction pathways.

PMID- 10080921
TI  - The phnIJ genes encoding acetaldehyde dehydrogenase (acylating) and 4-hydroxy-2
      oxovalerate aldolase in Pseudomonas sp. DJ77 and their evolutionary implications.
AB  - The two final steps of meta-cleavage pathway for catechol degradation involve
      conversion of 4-hydroxy-2-oxovalerate, via acetaldehyde, to acetyl coenzyme A. We
      report here the complete nucleotide sequences and overexpression of the phnIJ
      genes for an acetaldehyde dehydrogenase (acylating) (ADA) and a 4-hydroxy-2
      oxovalerate aldolase (HOA) from the meta-pathway operon of the phenanthrene
      degrading bacterium, Pseudomonas sp. strain DJ77. Additional partial sequence
      analysis of adjacent DNA shows the gene order within the operon to be phnHIJ,
      identical to the order found for the isofunctional genes in the other meta
      pathway operons. The deduced amino acid sequences of the PhnI (312 amino acids)
      and PhnJ (343 amino acids) have identities of 51-71% with the corresponding genes
      of dmp, xyl, nah, bph_LB400, bph_KKS102, tod, cum, cmt, and MTCY03C7 operons. The
      phylogenetic analyses reveal the evolutionary relationships of HOA and ADA.

PMID- 10080922
TI  - The IalA invasion gene of Bartonella bacilliformis encodes a (de)nucleoside
      polyphosphate hydrolase of the MutT motif family and has homologs in other
      invasive bacteria.
AB  - The product of the ialA invasion gene of Bartonella bacilliformis has been
      expressed as a thioredoxin fusion protein. It is a (di)nucleoside polyphosphate
      hydrolase of the MutT motif protein family with strong sequence similarity to
      plant diadenosine tetraphosphate hydrolases. It hydrolyses nucleoside and
      dinucleoside polyphosphates with four or more phosphate groups, always producing
      an NTP as one product. Diadenosine tetraphosphate (Ap4A) is the preferred
      substrate with a Km of 10 microM and a kcat of 3.0 s-1. It is inhibited by Ca2+
      and F- (Ki = 30 microM). Hydrolysis of Ap4A in H218O yielded [18O]AMP as the only
      labelled product. In terms of sequence, reaction mechanism and properties, IalA
      is very similar to eukaryotic Ap4A hydrolases and unlike previously described
      bacterial Ap4A hydrolases. Homologs are present in the genomes of other invasive
      pathogens. They may function to reduce stress-induced dinucleotide levels during
      invasion and so enhance pathogen survival.

PMID- 10080923
TI  - Tyrosine phosphorylation of STAT3 by leptin through leptin receptor in mouse
      metaphase 2 stage oocyte.
AB  - Leptin is the product of the obese gene (ob), and is secreted in plasma from
      mature adipocytes. It has been recently reported that leptin is synthesized in
      granulosa and cumulus cells within the follicle of the ovary, and is present in
      mature human oocytes, suggesting possible roles of leptin in several aspects of
      pre- and post-ovulatory follicular development. On the other hand, STAT (Signal
      Transducer and Activator of Transcription) transcription factors are involved in
      leptin-associated signal transduction. In this report, we studied the expression
      of leptin receptor and STAT3 activation by leptin in metaphase 2 stage (M2)
      oocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunoblotting showed that mRNA and protein of leptin receptor were expressed in
      M2 stage oocyte. Leptin at 15 ng/ml, the concentration observed in follicular
      fluid, caused tyrosine phosphorylation of STAT3 in mouse M2 stage oocytes. These
      results suggest possible roles of leptin in several aspects during oocyte
      maturation by activating the STAT signal transduction pathway.

PMID- 10080924
TI  - Mycobacterium tuberculosis KatG is a peroxynitritase.
AB  - Mycobacterium tuberculosis resides within the highly oxidative environment of the
      human macrophage and previous reports have indicated that these mycobacteria are
      susceptible to reactive nitrogen intermediates including peroxynitrite. This work
      provides evidence that the Mycobacterium tuberculosis hemoprotein KatG acts as an
      efficient peroxynitritase exhibiting a kapp of 1.4 x 10(5) M-1s-1 for
      peroxynitrite decomposition at pH 7.4 and 37 degrees C. The ability of KatG to
      act as a peroxynitritase adds to its growing list of enzymatic activities and may
      in part explain the ability of Mycobacterium tuberculosis to persist in
      macrophages.

PMID- 10080925
TI  - A core promoter and a frequent single-nucleotide polymorphism of the mismatch
      repair gene hMLH1.
AB  - The hMLH1 gene encodes a protein that is involved in the DNA mismatch repair
      system. The coding region of the hMLH1 gene has been known to be mutated in a
      subset of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Our
      current research characterized the promoter region of the hMLH1 gene and searched
      for mutations correlating to HNPCC. Utilizing the oligo-capping method, major
      transcription start sites of the hMLH1 gene were mapped at two locations. The
      core promoter region of about 180 bp was determined by the luciferase assay of
      serial deletion mutants. Although we did not find any pathogenic mutation in the
      hMLH1 promoter region by PCR-SSCP, we found a single-nucleotide polymorphism at
      position -93 nt from the adenine residue of the start codon. By PCR-RFLP analysis
      with Pvu II for this polymorphism, we detected LOH in four tumors from three
      patients. An easy detection of this polymorphism with PCR-RFLP and high incidence
      ( approximately 50%) of informative cases make this polymorphism a suitable
      marker for the detection of hMLH1 allelic losses.

PMID- 10080926
TI  - Widespread distribution of orexin in rat brain and its regulation upon fasting.
AB  - Orexins A and B, novel hypothalamic peptides encoded by a single mRNA transcript,
      stimulate food intake. Two antisera specific for the individual rat orexins were
      prepared and sensitive RIAs developed. Orexin-A and -B are abundant in the rat
      hypothalamus, medulla-pons, and midbrain-thalamus, and moderately abundant in the
      cerebral cortex. No orexins were found in the adipose tissues or visceral organs
      studied. The major endogenous molecule of orexin-A is a 33-amino-acid peptide,
      and that of orexin-B a 28-amino-acid peptide. After a 48 h fast, the orexin-A and
      -B contents of the lateral hypothalamus exhibited a trend to increase, but the
      contents of other brain tissues significantly decreased as compared with the fed
      control rats. No circadian variations in the orexin contents were found in the
      brain. The extensive and abundant distribution of orexins in the brain and
      changes in their contents upon fasting suggest that they serve as neuromodulators
      and/or neurotransmitters that regulate feeding behavior through interaction with
      diverse neural networks.

PMID- 10080927
TI  - Addition of veratryl alcohol oxidase activity to manganese peroxidase by site
      directed mutagenesis.
AB  - Manganese peroxidase and lignin peroxidase are ligninolytic heme-containing
      enzymes secreted by the white-rot fungus Phanerochaete chrysosporium. Despite
      structural similarity, these peroxidases oxidize different substrates. Veratryl
      alcohol is a typical substrate for lignin peroxidase, while manganese peroxidase
      oxidizes chelated Mn2+. By a single mutation, S168W, we have added veratryl
      alcohol oxidase activity to recombinant manganese peroxidase expressed in
      Escherichia coli. The kcat for veratryl alcohol oxidation was 11 s-1, Km for
      veratryl alcohol approximately 0.49 mM, and Km for hydrogen peroxide
      approximately 25 microM at pH 2.3. The Km for veratryl alcohol was higher and Km
      for hydrogen peroxide was lower for this manganese peroxidase mutant compared to
      two recombinant lignin peroxidase isoenzymes. The mutant retained full manganese
      peroxidase activity and the kcat was approximately 2.6 x 10(2) s-1 at pH 4.3.
      Consistent with relative activities with respect to these substrates, Mn2+
      strongly inhibited veratryl alcohol oxidation. The single productive mutation in
      manganese peroxidase suggested that this surface tryptophan residue (W171) in
      lignin peroxidase is involved in catalysis.

PMID- 10080928
TI  - Colocalization of GLUT3 and choline acetyltransferase immunoreactivity in the rat
      retina.
AB  - Toward elucidating the functional aspects ofGLUT3, a primary neuronal glucose
      transporter isoform in the vertebrate central nervous system, this study examined
      its expression in cholinergic amacrine cells made identifiable by the presence of
      acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT), in the rat
      retina. Double-immunofluorescence staining of adult rat retinal tissue with anti
      GLUT3 and anti-ChAT antibodies revealed characteristic stratified GLUT3
      immunoreactivity (GLUT3-IR) in the inner plexiform layer (IPL) that was identical
      to the arborization pattern of ChAT-positive neuronal processes there. In
      addition, approximately 30-50% of intensely GLUT3-immunoreactive cell bodies in
      the inner nuclear layer and ganglion cell layer showed ChAT-IR, while the
      majority of ChAT-positive cell bodies were also intensely GLUT3 immunoreactive.
      Analysis at the cellular level using retinal cells in culture revealed similar
      findings. These results collectively indicate that cholinergic amacrine cells
      constitute the major component of GLUT3-expressing cells in the rat retina. It is
      expected that the link demonstrated here between GLUT3 expression and cholinergic
      amacrine cell population will provide clues for further analyzing GLUT3 function
      in the retina.

PMID- 10080929
TI  - Carboxyl-terminal fragments of presenilin-1 are closely related to cytoskeletal
      abnormalities in Alzheimer's brains.
AB  - To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's
      disease (AD), we tested four antisera to PS-1. The specific antisera to the N
      terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a
      25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in
      COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their
      amounts were not significantly different between the control and AD brains. The
      antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and
      curly fibers in the AD brains. In the paired helical filament (PHF) fraction
      containing A68 protein from AD brains, a smear pattern of CTFs was revealed.
      Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed
      immunoreactive neurofibrillary tangles in the AD brain sections and the smear
      pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF
      tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities
      in AD brains.

PMID- 10080930
TI  - Expression of CD30 ligand (CD153) on murine activated T cells.
AB  - CD30, a member of the TNF receptor family, has been implicated in the activation
      of T cells and B cells. In the present study, we characterized the expression and
      function of murine CD30 ligand (mCD153) by utilizing mCD153 transfectants and a
      novel mAb against mCD153 (RM153), which can inhibit the binding of murine CD30 to
      mCD153. The mCD153 transfectants did not co-stimulate the proliferation of anti
      CD3-stimulated naive T cells but enhanced the proliferation of anti-CD28-co
      stimulated T cells. The mCD153 transfectants exhibited a potent co-stimulatory
      activity for proliferation of pre-activated T cells that expressed CD30 after
      anti-CD3 and anti-CD28 stimulation. In contrast to the CD30 expression on naive T
      cells that required anti-CD28 co-stimulation, mCD153 expression was observed on
      anti-CD3-stimulated T cells without the anti-CD28 co-stimulation, predominantly
      on CD4(+) T cells with a transient kinetics which peaked at 24 h but disappeared
      at 48 h. In contrast to the preferential expression of CD30 on Th2 cells, mCD153
      was expressed on both Th1 and Th2 cells after anti-CD3 stimulation. These results
      indicated a differential regulation of CD30 and CD153 expression in T cells,
      which may be relevant to immuno-regulatory role of the CD30-CD153 interaction.

PMID- 10080931
TI  - Expression of osteopontin in Kupffer cells and hepatic macrophages and Stellate
      cells in rat liver after carbon tetrachloride intoxication: a possible factor for
      macrophage migration into hepatic necrotic areas.
AB  - Activated Kupffer cells and macrophages accumulate in necrotic areas in the
      liver. Osteopontin, an extracellular matrix with RGD sequence, has been shown to
      act as a chemokine that can induce monocyte migration. The possibility that
      osteopontin can play a role in infiltration of both cells into hepatic necrotic
      areas was investigated in rats. Northern blot analysis revealed that osteopontin
      mRNA expression was minimal in Kupffer cells and hepatocytes immediately after
      isolation from normal rats, but slight in hepatic stellate cells assumed nearly
      quiescent in function after 3 days of culture on plastic dishes. When rat
      received carbon tetrachloride, liver necrosis developed between 1 and 3 days
      following the intoxication. In these rats, osteopontin mRNA expression assessed
      by quantitative competitive RT-PCR was increased in the liver later than 1 day
      with its peak at 2 days following the intoxication. Kupffer cells and hepatic
      macrophages and hepatic stellate cells isolated from such liver showed marked
      expression of osteopontin mRNA on Northern blotting. Immunohistochemical
      examination disclosed that osteopontin was stained in macrophages including
      Kupffer cells and stellate cells in the necrotic areas. On electron microscopy,
      osteopontin stains were present in the Golgi apparatus in these cells.
      Recombinant human osteopontin promoted migration of Kupffer cells isolated from
      normal rats and cultured in a Transwell cell culture chamber in a dose-related
      manner. We conclude that activated Kupffer cells and hepatic macrophages and
      stellate cells express osteopontin. These cells might contribute to the
      infiltration of Kupffer cells and macrophages into hepatic necrotic areas by
      expressing osteopontin.

PMID- 10080932
TI  - Recognition of sequence-directed structure of the ssDNA backbone by nucleases.
AB  - Escherichia coli endonuclease I and exonuclease VII appear to recognize sequence
      dependent conformations in the ssDNA backbone. ssDNAs, containing either A-
      and/or T-tract or a CAP binding region, were digested with these nucleases under
      conditions which minimize the formation of secondary structures. The digestion
      patterns were examined in relation to previous results of biochemical and
      crystallographic studies on dsDNA, and showed broad agreement. Endonuclease I
      cleaved ssDNA at sites corresponding to bent sites in dsDNA.

PMID- 10080933
TI  - Combinatorial chemistry reveals a new motif that binds the platelet fibrinogen
      receptor, gpIIbIIIa.
AB  - Among cell adhesion molecules, the classic Arg-Gly-Asp (RGD) motif is the best
      studied. We used combinatorial chemical and affinity immunochemical methods to
      find a novel motif of unnatural peptide ligands for the fibrinogen receptor of
      platelets, gpIIbIIIa (alphaIIbbeta3). The new d-amino acid motif, p(f/y)l, is
      unique among the ligands that bind the RGD pocket: It lacks the carboxylic acid
      group that is believed to coordinate with calcium in the MIDAS motif of the
      receptor. With an IC50 of 14 microM for the most potent compound, these linear
      p(f/y)l peptides had affinities similar to those of linear peptides containing
      RGD, and reversed sequences failed to compete with binding up to 1 mM. As the new
      motif was so different, molecular modeling was employed to suggest a model for
      molecular recognition. A reversed binding mechanism common for d-amino acid
      mimics of natural l-amino acid peptides offers an attractive hypothesis that
      suggests three points of contact similar to those made by the RGD-mimicking
      monoclonal antibody, OPG2. Interestingly, the model proposes that pi-electrons in
      the new motif may substitute for the carboxylate group present in all other RGD
      types of ligands. Although modeling linear peptides is subjective, the pi-bonding
      model provides intriguing possibilities for medicinal chemistry after appropriate
      confirmatory studies.

PMID- 10080934
TI  - Expression of human perlecan domain I as a recombinant heparan sulfate
      proteoglycan with 20-kDa glycosaminoglycan chains.
AB  - Recombinant forms of human perlecan domain I were secreted as proteoglycans by
      stably transfected human 293 cells. A recombinant domain I-only proteoglycan
      spanned the 95- to 265-kDa region in SDS-PAGE and appeared to be 160 kDa in
      denaturing gel filtration. Its glycosaminoglycan (GAG) content was approximately
      67% heparan sulfate, and its average GAG chain size of 20 kDa suggested that the
      true molecular mass of the proteoglycan was 90 kDa. Domain I with enhanced green
      fluorescent protein fused to its C-terminus had an apparent molecular mass of 210
      220 kDa and contained approximately 100% heparan sulfate. Its average GAG chain
      size (also 20 kDa) suggested a true molecular mass of 117 kDa for this
      proteoglycan. Its sulfate content of 53-77 mol SO2-4 per mole of protein
      indicated the presence of one sulfate group per 4-7 GAG sugar residues.

PMID- 10080935
TI  - Characterization of the advanced glycation end-product receptor complex in human
      vascular endothelial cells.
AB  - Advanced glycation end products (AGEs) have been implicated as causal factors in
      the vascular complications of diabetes and it is known that these products
      interact with cells through specific receptors. The AGE-receptor complex,
      originally described as p60 and p90, has been characterised in hemopoietic cells
      and the component proteins identified and designated AGE-R1, -R2 and -R3. In the
      current study we have characterised this receptor in human umbilical vein
      endothelial cells (HUVECs) and elucidated several important biological properties
      which may impact on AGE mediated vascular disease. 125I-AGE-BSA binding to HUVEC
      monolayers was determined with and without various cold competitors. The
      synthetic AGE, 2-(2-furoyl)-4(5)-furanyl-1H-imidazole (FFI)-BSA, failed to
      compete with AGE-BSA binding unlike observations already reported in hemopoietic
      cells. The ability of 125I-AGE-BSA to bind to separated HUVEC plasma membrane
      (PM) proteins was also examined and the binding at specific bands inhibited by
      antibodies to each component of the AGE-receptor complex. Western blotting of
      whole cell and PM fractions, before and after exposure to AGE-BSA, revealed that
      AGE-R1, -R2 and -R3 are subject to upregulation upon exposure to their ligand, a
      phenomenon which was also demonstrated by immunofluorescence of non-permeabilised
      cells. mRNA expression of each AGE-receptor component was apparent in HUVECs,
      with the AGE-R2 and -R3 gene expression being upregulated upon exposure to AGEs
      in a time-dependent manner. A phosporylation assay in combination with AGE-R2
      immunoprecipitation demonstrated that this component of the receptor complex is
      phosphorylated by acute exposure to AGE-BSA. These results indicate the presence
      of a conserved AGE-receptor complex in vascular endothelium which demonstrates
      subtle differences to other cell-types. In response to AGE-modified molecules,
      this complex is subject to upregulation, while the AGE-R2 component also displays
      increased phosphorylation possibly leading to enhanced signal transduction.

PMID- 10080936
TI  - Human achaete-scute homologue 1 (HASH-1) is downregulated in differentiating
      neuroblastoma cells.
AB  - The mammalian achaete-scute homologue, MASH-1, is crucial for early development
      of the sympathetic nervous system and is transiently expressed in sympathetic
      neuroblasts during embryogenesis. Here we report that the human homologue (HASH
      1) was expressed in all analyzed cell lines (6/6) derived from the sympathetic
      nervous system tumor neuroblastoma. The majority of small-cell lung carcinoma
      (4/5) cell lines tested expressed HASH-1, while other nonneuronal/non
      neuroendocrine cell lines were negative. Induced differentiation of neuroblastoma
      cells resulted in HASH-1 downregulation. This occurred concomitant with induction
      of neurite outgrowth and expression of the neuronal marker genes GAP-43 and
      neuropeptide Y. Constitutive expression of exogenous HASH-1 did not alter the
      capacity of the neuroblastoma cells to differentiate in response to
      differentiation-inducing agents. It is concluded that moderate HASH-1 expression
      does not compromise the capacity of these cells to differentiate.

PMID- 10080937
TI  - Purification and characterization of human metallocarboxypeptidase Z.
AB  - Carboxypeptidase Z (CPZ) is a recently discovered member of the
      metallocarboxypeptidase gene family that has an N-terminal domain related to the
      Wnt/wingless binding domain of frizzled receptors and other proteins. To further
      characterize the enzymatic properties of CPZ, the enzyme was purified using Arg-
      and heparin-affinity columns. CPZ has a neutral pH optimum, and is inhibited by
      chelating agents and several divalent cations (Zn2+, Mn2+, Cd2+, Cu2+, Hg2+).
      Active site-directed inhibitors of several other metallocarboxypeptidases also
      inhibit CPZ activity with moderate potency. CPZ cleaves substrates with C
      terminal Arg residues, preferring peptides with an Ala in the penultimate
      position. No activity is detected toward substrates with an Ile-Arg or a Pro-Arg
      sequence. The Km for dansyl-Phe-Ala-Arg and dansyl-Pro-Ala-Arg are both
      approximately 2 mM. Taken together, these data suggests a selective role for CPZ
      in the processing of extracellular peptides or proteins.

PMID- 10080938
TI  - Protein S-myristoylation in Leishmania revealed with a heterologous reporter.
AB  - Reversible esterification of myristic acid to cysteine residue(s) (S
      myristoylation) was documented recently in the protozoan Trypanosoma brucei.
      Unlike N-myristoylation, S-myristoylation appears to be rare (or non-existent) in
      animal cells and has not been documented in any other trypanosome. Reasoning that
      a lack of knowledge of appropriate substrates may have contributed to this state
      of affairs, we devised an assay to test for protein S-myristoylation in the
      ancient eukaryote Leishmania. A cDNA encoding a glycosylphosphatidylinositol
      phospholipase C (GPI-PLC) from T. brucei was transfected into Leishmania and the
      expressed protein analyzed for covalent lipid modifications. Leishmania modified
      the reporter with myristate in a thio-ester linkage. From these observations, we
      infer that (i) GPI-PLC may be used as a reporter of this lipid modification in
      eukaryotes, and (ii) protein S-myristoylation might have ancient origins.

PMID- 10080939
TI  - ZF5, which is a Kruppel-type transcriptional repressor, requires the zinc finger
      domain for self-association.
AB  - ZF5, which we have cloned as a transcriptional repressor on the mouse c-myc
      promoter, has the POZ domain at the amino-terminus and the Kruppel-type zinc
      finger domain at the carboxy-terminus. In this report, we showed that ZF5 has two
      contradictory functions in transcription: activation of human immunodeficiency
      virus (HIV) promoter and repression of the HSV thymidine kinase (TK) promoter.
      The POZ domain contributed to the repressor activity, whereas the active function
      resulted from the DNA-binding ability of the zinc finger domain. We demonstrated
      that the POZ domain has a function mediating homomeric protein-protein
      interaction and this interaction requires the zinc finger domain. Furthermore,
      the POZ domain decreased the DNA-binding activity of the zinc finger domain.
      These results can provide evidence indicating the important interaction between
      the POZ and zinc finger domains.

PMID- 10080940
TI  - Distinct characteristics of receptor-operated Ca2+ influx and refilling in
      pancreatic acinar cells.
AB  - Ca2+ influx from the extracellular space in nonexcitable cells occurs via
      receptor-operated and refilling processes. However, they showed different
      characteristics with respect to the Mn2+ permeability, depletion of intracellular
      Ca2+ stores, and sensitivity to the K+ ionophore valinomycin in rat pancreatic
      acinar cells. While Mn2+ did not enter into the cells during the refilling phase,
      the opposite was true in receptor-operated Ca2+ influx (ROCI) evoked by carbachol
      (CCh). ROCI occurred in the absence of intracellular Ca2+ release from the
      stores. Valinomycin abolished the second response of Ca2+ elicited by CCh,
      whereas it had no effect on ROCI. These observations suggest that receptor
      operated Ca2+ channels (ROCCs) and refilling channels may be different in rat
      pancreatic acinar cells.

PMID- 10080941
TI  - Identification of Tcf4 residues involved in high-affinity beta-catenin binding.
AB  - The N-termini of members of the T-cell factor (Tcf) and lymphocyte-enhancement
      factor (Lef) protein families bind to beta-catenin, forming bipartite
      transcription factors which regulate expression of genes involved in organismal
      development and the growth of normal and malignant colon epithelium. Elevated
      levels of Tcf4:beta-catenin are found in colon tumor cells with mutations in the
      adenomatous polyposis coli (APC) gene. The elevated levels of Tcf4:beta-catenin
      result in increased transcription of genes, including c-myc, important for the
      growth of these tumor cells. Here we analyze the interaction between beta-catenin
      and Tcf4 and show that the N-terminal 53 amino acids of Tcf4 bind with high
      affinity to beta-catenin. We show that this high-affinity interaction involves
      multiple contact points including Tcf4 Asp-16, which is essential for beta
      catenin binding. In addition to Tcf/Lef family members, beta-catenin binds to APC
      and cadherins. We found that the binding of beta-catenin to Tcf4, APC, or E
      cadherin was mutually exclusive. These results are discussed with regard to how
      beta-catenin interacts with its binding partners and to the potential for
      identifying specific, small molecule inhibitors of these interactions.

PMID- 10080942
TI  - Structural requirements of a human deoxyribonuclease II for the development of
      the active enzyme form, revealed by site-directed mutagenesis.
AB  - Using site-directed mutagenesis, we eliminated three potential N-glycosylation
      sites (N86, N212, and N266) of human deoxyribonuclease II (DNase II), conserved
      in mammalian enzymes, and a proteolytic processing site (Q46-R47), forming a
      propeptide subunit of the enzyme. We expressed a series of these mutant DNase II
      constructs in COS-7 and Hep G2 cells. Liberation of each glycosylation site at
      N86 and N266 and the cleavage site interfered dramatically with expression of the
      intracellular and secreted DNase II activities, irrespective of cell line
      transfected. A chimeric mutant in which the signal peptide of the DNase II was
      replaced with that of human DNase I had no intracellular or secreted enzyme
      activity. Therefore, a simultaneous attachment of a carbohydrate moiety to N86
      and N266, cleavage of the propeptide from the single DNase II precursor, and the
      inherent signal peptide might be required for subcellular sorting and proteolytic
      maturation of the enzyme.

PMID- 10080943
TI  - Lack of correlation in JNK activation and p53-dependent Fas expression induced by
      apoptotic stimuli.
AB  - Induction of Fas expression by DNA-damaging agents is dependent on the expression
      of functional p53, and has been suggested to play an important role in apoptosis
      induction. JNK (c-Jun N-terminal kinase), which is capable of phosphorylating
      p53, is also involved in apoptotic signaling induced by various apoptotic
      stimuli. Here, we report that although Fas induction is closely linked to the
      expression of wild type p53, it is not correlated with JNK activation induced by
      apoptotic stimuli. JNK activation does not necessarily lead to Fas expression,
      even in cells containing wild type p53. In addition, Fas expression can be
      induced without significant JNK activation. Furthermore, induction of Fas
      expression is not sufficient for apoptosis induction; however, it may sensitize
      cells to Fas-ligation induced apoptosis.

PMID- 10080944
TI  - A role for leptin in brain development.
AB  - Leptin, the product of the obese gene, is a circulating hormone involved in
      feeding behavior and energy homeostasis. Ob/ob mice which are leptin deficient
      have many phenotypic abnormalities including brains that are smaller in both
      weight and cortical volume. To this end, we monitored the effects of leptin
      administration on brain growth. Intraperitoneal administration of leptin for 2
      weeks daily to 4-week-old ob/ob mice resulted in a maximal 10% increase in both
      wet and dry brain weights. This increase appears to be partially the result of
      increased cell number as indicated by a 19% increase in total brain DNA. In
      summary, our data suggest that the decreased brain size of the ob/ob mouse is due
      to a developmental defect that can be corrected upon leptin administration and
      therefore leptin plays a role in brain growth and development.

PMID- 10080945
TI  - STAT-1-independent upregulation of FADD and procaspase-3 and -8 in cancer cells
      treated with cytotoxic drugs.
AB  - We have previously shown that treatment by anticancer drugs sensitized tumor
      cells to Fas (APO-1/CD95)-mediated cell death. The present study demonstrates
      that the cytotoxic drugs cisplatin, doxorubicin and mitomycin C induce the
      accumulation of the Fas receptor, the FADD adaptor molecule, the procaspases-8, 
      3 and -2L and the proapoptotic molecule Bax in several human colon cancer cells.
      This upregulation is also observed in U3A myeloblastoma cells that do not express
      STAT-1, a transcription factor involved in the constitutive expression of
      procaspases. We conclude that anticancer drugs sensitize tumor cells to Fas
      mediated cell death by a STAT-1-independent upregulation of molecules involved in
      this apoptotic pathway.

PMID- 10080946
TI  - The immediate early gene products of human cytomegalovirus increase vascular
      smooth muscle cell migration, proliferation, and expression of PDGF beta
      receptor.
AB  - Evidence suggests that human cytomegalovirus (HCMV) infection contributes to the
      development of atherosclerosis and restenosis. Because smooth muscle cell (SMC)
      proliferation and migration are crucial events of both processes, and because
      PDGF beta-receptor modulates SMC migration, we determined whether HCMV infection
      affects SMC proliferation, migration, and PDGF beta-receptor expression. We
      employed a SMC model in which HCMV infection leads to expression of only the
      immediate early (IE) HCMV gene products-HCMV infection of rat SMCs. We found that
      HCMV infection significantly (i) increased SMC proliferation (from 0.9 x 10(6) +/
      0.024 x 10(6) to 1.4 x 10(6) +/- 0.051 x 10(6) cells/well, p < 0.001); (ii)
      augmented SMC migration toward PDGF (from 64 +/- 37 to 116 +/- 51 cells/high
      power field; p < 0.01); and (iii) enhanced PDGF beta-receptor expression in a
      time-dependent fashion. We conclude that HCMV infection of rat SMCs increases SMC
      proliferation, migration, and PDGF beta-receptor expression. These findings
      identify further mechanisms by which CMV may contribute to the development of
      atherosclerosis and restenosis.

PMID- 10080947
TI  - Expression of the dominant-negative regulator Id4 is induced during adipocyte
      differentiation.
AB  - Expression of the Id4 gene was investigated during differentiation of 3T3-L1
      preadipocytes into mature adipocytes. Id4 is a member of a family encoding non
      DNA binding helix-loop-helix proteins proposed to inhibit the activity of basic
      HLH (bHLH) proteins important in many developmental processes. We show here that
      Id4 expression is low in confluent preadipocytes and rapidly induced by treatment
      with the combination of hormones which causes differentiation into mature
      adipocytes. Id4 expression is also induced by treatment with individual hormones,
      especially dexamathasone. Id4 mRNA can be detected in mouse and human adipose
      tissue. Genes encoding E-proteins (bHLH proteins known to interact with and be
      regulated by Id proteins) are expressed and regulated during differentiation in
      3T3-L1 cells. These data suggest that the Id4 transcriptional regulator is
      playing a role in adipose cell differentiation and suggest that DNA-binding HLH
      proteins may also be important in regulation of differentiation of these cells.

PMID- 10080948
TI  - Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain.
AB  - TRAF2 is a signal transducing adaptor molecule which binds to the CD40
      cytoplasmic domain. We have found that it is phosphorylated, predominantly on
      serine residues, when transiently overexpressed in 293 cells. The phosphorylation
      appears to be related to the signaling events that are activated by TRAF2 under
      these circumstances, since two nonfunctional mutants were found to be
      phosphorylated significantly less than the wild-type protein. Furthermore, the
      phosphorylation status of TRAF2 had significant effects on the ability of the
      protein to bind to CD40, as evidenced by our observations that the CD40
      cytoplasmic domain interacted preferentially with underphosphorylated TRAF2 and
      that phosphatase treatment significantly enhanced the binding of TRAF2 to CD40.
      We conclude from these studies that the phosphorylation of TRAF2 is likely to
      play an important role in regulating signaling by virtue of its ability to
      influence the CD40-TRAF2 interaction.

PMID- 10080949
TI  - alpha-thrombin inhibits interleukin-6-induced Stat3 signaling and gp130 gene
      expression in primary cultures of human lung fibroblasts.
AB  - Exposure of primary human lung fibroblasts (HLF) to interleukin-6 (IL-6) rapidly
      induced Stat3 (signal transducers and activators of transcription 3) tyrosine
      phosphorylation. In these cells, alpha-thrombin did not induce tyrosine
      phosphorylation of Stat3; however, it potently induced its serine
      phosphorylation. Interestingly, a short pretreatment of cells with alpha-thrombin
      significantly inhibited IL-6-induced tyrosine phosphorylation of Stat3. The
      inhibition by alpha-thrombin was attenuated if cells were pretreated with U0126,
      a specific inhibitor of the mitogen-activated protein (MAP) kinase kinase 1
      (MAPKK1). Exposure of HLF cells to IL-6 induced a twofold increase in gp130 mRNA
      levels; however, alpha-thrombin inhibited this IL-6-induced response almost to
      control levels. These results demonstrate, for the first time, that in HLF cells
      alpha-thrombin inhibits IL-6-induced Stat3 signaling via activation of MAPKK1 and
      that this cross-talk regulates IL-6-induced gp130 gene expression.

PMID- 10080950
TI  - Cell surface n-acetylneuraminic acid alpha2,3-galactoside-dependent intercellular
      adhesion of human colon cancer cells.
AB  - Sialoglycans on the cell surface of human colon cancer (HCC) cells have been
      implicated in cellular adhesion and metastasis. To clarify the role of N
      acetylneuraminic acid (NeuAc) linked alpha2,3 to galactose (Gal) on the surface
      of HCC cells, we studied the intercellular adhesion of HCC cell lines expressing
      increasing NeuAcalpha2,3Gal-R. Our model system consisted of the HCC SW48 cell
      line, which inherently possesses low levels of cell surface alpha2,3 and alpha2,6
      sialoglycans. To generate SW48 clonal variants with elevated cell surface
      NeuAcalpha2,3Gal-R linkages, we transfected the expression vector, pcDNA3,
      containing either rat liver cDNA encoding Galbeta1,3(4)GlcNAc alpha2,3
      sialyltransferase (ST3Gal III) or human placental cDNA encoding
      Galbeta1,3GalNAc/Galbeta1,4GlcNAc alpha2,3 sialyltransferase (ST3Gal IV) into
      SW48 cells. Selection of neomycin-resistant clones (600 microgram G418/ml) having
      a higher percentage of cells expressing NeuAcalpha2,3Gal-R (up to 85% positive
      Maackia amurenis agglutinin staining compared with 30% for wild type cells) was
      performed. These ST3Gal III and ST3Gal IV clonal variants demonstrated increased
      adherence to IL-1beta-activated human umbilical vein endothelial cells (HUVEC)
      (up to 90% adherent cells compared with 63% for wild type cells). Interestingly,
      ST3Gal III and ST3Gal IV clonal variants also bound non-activated HUVEC up to 4
      fold more effectively than wild type cells. Cell surface NeuAcalpha2,3Gal-R
      expression within the various SW48 clonal variants correlated directly with
      increased adhesion to HUVEC (r=0.84). Using HCC HT-29 cells, which express high
      levels of surface NeuAcalpha2,3Gal-R, addition of synthetic sialyl, sulfo or
      GalNAc Lewis X structures were found to specifically inhibit intercellular
      adhesion. At 1.0mM, NeuAcalpha2,3Galbeta1,3(Fucalpha1, 4)GlcNAc-OH and
      Galbeta1,4(Fucalpha1,3)GlcNAcbeta1,6(SE-6Galbeta1++ +, 3)GalNAcalpha1-O-methyl
      inhibited HT-29 cell adhesion to IL-1beta-stimulated HUVEC by 100% and 68%,
      respectively. GalNAcbeta1, 4(Fucalpha1,3)GlcNAcbeta1-O-methyl and
      GalNAcbeta1,4(Fucalpha1, 3)GlcNAcbeta1,6Manalpha1,6Manbeta1-0-C30H61, however,
      did not possess inhibitory activity. In conclusion, these studies demonstrated
      that cell surface NeuAcalpha2,3Gal-R expression is involved in HCC cellular
      adhesion to HUVEC. These specific carbohydrate-mediated intercellular adhesive
      events may play an important role in tumor angiogenesis, metastasis and growth
      control.

PMID- 10080951
TI  - Effects of acute or prolonged exposure to human leptin on isolated human islet
      function.
AB  - The adipocyte-derived hormone leptin has been reported to inhibit, have no
      effect, or potentiate insulin secretion in-vitro; these effects mainly depend on
      the species considered, the concentrations used, and the length of exposure. We
      investigated the direct effects of recombinant human leptin (HL) on human
      pancreatic beta cell function by studying insulin secretion (IS), hexokinase and
      glucokinase activity and Km, and potassium channel permeability in purified human
      islets (HI). In acute experiments, no effect of 1, 5, 20, or 50 ng/ml HL on
      glucose or arginine stimulated insulin release was found, whereas 500 ng/ml HL
      caused a significant decrease of glucose induced IS. After 24h pre-culture with
      either 20 or 500 ng/ml HL, a significant reduction of glucose (but not arginine)
      stimulated IS was observed. Exposure to leptin caused a significant increase of
      potassium channel permeability, whereas hexokinase and glucokinase activity and
      Km remained unchanged. These results suggest that physiological human leptin
      concentration is able to importantly affect glucose (but not arginine) stimulated
      insulin release from human islets only after prolonged exposure. This effect is
      probably mediated by changes of potassium channel permeability, and is not
      accompanied by modifications of glucose phosphorylating enzymes properties.

PMID- 10080952
TI  - A 16-kDa fragment of collagen type XIV is a novel neutrophil chemotactic factor
      purified from rat granulation tissue.
AB  - A neutrophil chemotactic factor has been purified from the homogenate of rat
      granulation tissues. The purified chemoattractant was a basic protein with
      heparin-binding site and gave a single band corresponding to a molecular mass of
      16 kDa on SDS-PAGE under reducing conditions. The chemoattractant was treated
      with lysylendopeptidase and the resulting peptides were isolated by reversed
      phase HPLC. Amino acid sequences of the peptides were almost identical with the
      sequence of N-terminal fibronectin type III domain of human collagen type XIV,
      suggesting that the purified chemoattractant consists mainly of N-terminal
      fibronectin type III domain and the adjacent heparin-binding site of rat collagen
      type XIV. The 16-kDa fragment of collagen type XIV dose dependently attracted rat
      neutrophils and transiently increased the intracellular free Ca2+ concentration
      of neutrophils. The results suggest that the novel chemoattractant plays a role
      in neutrophil recruitment in rat inflammation.

PMID- 10080953
TI  - Antizyme-dependent and -independent mechanisms are responsible for increased
      spermidine transport in amino acid-restricted human cancer cells.
AB  - Amino acid deprivation can inhibit tumour cell proliferation. Since polyamines
      are required for cell growth, we hypothesised that their regulatory pathways can
      respond to amino acid restriction. We report here that exposure of human colon
      adenocarcinoma Caco-2 cells to a medium restricted for a single amino acid, but
      not for D-glucose, activates spermidine transport. The increase was rapid and
      seemed transient with a maximum 4-6 hr after amino acid removal. Kinetics showed
      that the maximal velocity of transport was solely increased in L-methionine- or L
      leucine-deprived cells, indicating increased number of transporters. The
      intracellular level of complex of ornithine decarboxylase (ODC) with antizyme, a
      negative regulator of polyamine transport, was decreased by 16-29% in amino acid
      deprived cells. However, exposure to limited amounts of amino acid increased
      transport without altering the ODC-antizyme complex level. We propose that
      antizyme-independent mechanisms, sensitive to the amino acid concentration, also
      participate to the control of spermidine transport.

PMID- 10080954
TI  - Intense myristoylation of a single protein in the ocular lens.
AB  - A single protein of the ocular lens was intensely myristoylated following short
      term incubation of cultured bovine lens epithelial cells and intact rat lenses
      with 3H-myristic acid. It was acidic (pI <5), about 19 kDa and present
      exclusively in the cytosol of both cultured epithelial cells and the epithelium
      of the young rat lens. Fiber cell proteins were not labeled. The myristoylated
      protein was not seen in the epithelium of the adult rat. Essentially no protein
      mass was evident in the 19-20 kDa range when samples of the labeled-soluble
      protein were fractionated by either HPLC coupled with SDS-PAGE or 2D
      electrophoresis. These findings suggest that the myristoylated-soluble protein of
      19 kDa in lens (p19L) is a rapidly-turning over minor protein likely associated
      with lens growth. The absence of any apparent membrane association for a
      myristoylated protein appears unusual. The trace nature of p19L has frustrated
      attempts at its identification by MALDI-MS.

PMID- 10080955
TI  - Role of microphthalmia transcription factor in regulation of melanocyte
      differentiation marker TRP-1.
AB  - Tyrosinase and a family of tyrosinase-related proteins (TRPs) are melanocyte
      differentiation gene products involved in melanin pigmentation. Members of the
      tyrosinase family share upstream transcriptional regulatory elements suggesting
      that expression of these genes is regulated by shared mechanisms. Microphthalmia
      transcription factor MITF, a melanocyte-specific basic helix-loop-helix protein,
      has been shown to transactivate tyrosinase and TRP-1 genes in vitro by binding to
      a shared regulatory sequence known as M box. The role of MITF in concomitant
      regulation of these genes in vivo is not clear. We showed earlier that in human
      melanoma cells TRP-1 can be regulated independently of tyrosinase and
      pigmentation. To investigate the role of MITF in TRP-1 regulation, we studied the
      effect of pharmacological agents that modulate transcription of tyrosinase and
      TRP-1 on MITF. In melanoma cells treated with hexamethylene bisacetamide (HMBA),
      transcription of TRP-1 gene was selectively and completely inhibited while steady
      state levels of tyrosinase, TRP-2, MITF mRNA and melanin content showed a modest
      increase. HMBA caused no detectable change in cellular MITF or its nuclear
      localization. This MITF-independent regulation of TRP-1 required continued
      synthesis of RNA and protein. Selective down-regulation of TRP-1 by HMBA occurred
      even in the presence of cholera toxin which up-regulates TRP-1 by cAMP-mediated
      pathways. These data show that TRP-1 gene can be down-regulated independently of
      MITF by de novo activation of negative regulatory factors. Thus, both activation
      of positive factors such as MITF and inactivation of negative regulatory factors
      may be required for TRP-1 gene expression during melanocytic differentiation.

PMID- 10080956
TI  - PACAP is an islet neuropeptide which contributes to glucose-stimulated insulin
      secretion.
AB  - Pituitary adenylate cyclase activating peptide (PACAP) is a ubiquitously
      distributed neuropeptide which also is localized to pancreatic islets and
      stimulates insulin secretion. We examined whether endogenous PACAP within the
      islets might contribute to glucose-stimulated insulin secretion by
      immunoneutralizing endogenous PACAP. Immunocytochemistry showed that PACAP
      immunoreactivity is expressed in nerve terminals within freshly isolated rat
      islets, but not in islets that had been cultured for 48 h. In contrast, islet
      endocrine cells did not display PACAP immunoreactivity. Addition of either of two
      specific PACAP antisera markedly inhibited glucose (11.1 mmol/l)-stimulated
      insulin secretion from freshly isolated rat islets, whereas a control rabbit
      serum did not affect glucose-stimulated insulin secretion. In contrast, the PACAP
      antisera had no effect on glucose-stimulated insulin secretion in cultured
      islets. Based on these results we therefore suggest that PACAP is an islet
      neuropeptide which is required for the normal insulinotropic action of glucose.

PMID- 10080957
TI  - The Csk homologous kinase, Chk, binds tyrosine phosphorylated paxillin in human
      blastic T cells.
AB  - In determining the role of Chk in T cell signaling, we have focused on its
      protein-protein interactions. We detected a tyrosine phosphoprotein that
      coimmunoprecipitated with Chk from pervanadate stimulated human blastic T cells.
      Subsequent Western blot analysis identified this tyrosine phosphoprotein as
      paxillin. Paxillin, a cytoskeletal protein involved in focal adhesions, was first
      identified as a v-Src substrate in transformed fibroblasts. Interestingly, Chk
      specifically bound tyrosine phosphorylated paxillin. Consistent with our in vivo
      data, Chk and paxillin were observed to localize in similar cellular regions
      prior to and following stimulation. Using GST fusion proteins, we determined that
      the Chk SH2 domain, not the SH3 domain, bound tyrosine phosphorylated paxillin.
      Specifically, paxillin bound to the FLVRES motif of the Chk SH2 domain. Using Far
      Western analysis, we revealed that the Chk SH2 domain directly associates with
      tyrosine phosphorylated paxillin. Finally, p52(Chk) expression in Csk-deficient
      mouse embryo fibroblasts decreased total phosphotyrosine levels of paxillin,
      implying a physiological role for Chk. These studies provide important insight
      into the role of Chk in tyrosine mediated signaling, as well as T cell
      physiology.

PMID- 10080958
TI  - Inhibition of IRS-1 phosphorylation and the alterations of GLUT4 in isolated
      adipocytes from cachectic tumor-bearing rats.
AB  - Cellular and molecular mechanisms of insulin resistance in isolated adipocytes
      from methylcholanthrene-induced sarcoma-bearing rats were investigated by
      measuring 3-O-[14C]methyl glucose transport activity, glucose transporter-4
      (GLUT4) protein in both plasma membrane and low-density microsomes, and insulin
      stimulated tyrosine phosphorylation of the insulin receptor (IR) and insulin
      receptor substrate-1 (IRS-1). Compared to both pair-fed and freely fed controls,
      tumor-bearing rats (TBR) had a decreased insulin-stimulated glucose transport
      activity with a lower Vmax and a higher EC50. GLUT4 protein in low-density
      microsomes from adipocytes maintained at the basal state was less in TBR than in
      controls. In insulin-stimulated adipocytes, GLUT4 protein in plasma membranes was
      also less in tumor-bearing rats than in controls. Insulin-induced tyrosine
      phosphorylation of IRS-1 was less in TBR than controls, but that of the IR was
      similar among the three groups. These data suggest that the insulin resistance
      seen in adipose cells of these tumor-bearing rats was caused in part by a
      decreased amount of GLUT4 protein in both basal and insulin-stimulated states
      resulting from the selective inhibition of insulin-stimulated phosphorylation of
      IRS-1.

PMID- 10080959
TI  - Isoniazid accumulation in Mycobacterium smegmatis is modulated by proton motive
      force-driven and ATP-dependent extrusion systems.
AB  - Resistance to isoniazid (INH), a frontline, antituberculosis drug, presents a
      major problem in the chemotherapy of tuberculosis. Although several targets of
      INH have been identified, the mechanism of INH resistance remains incompletely
      understood. This report demonstrates that INH accumulation in Mycobacterium
      smegmatis is enhanced both upon addition of both a proton motive force (pmf)
      uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), and upon addition of
      ortho-vanadate, an inhibitor of ATP-dependent efflux pumps. Both the Deltapsi and
      DeltapH components of the pmf are likely to be involved as judged by the effects
      of valinomycin and nigericin, respectively. Reserpine, an inhibitor of the human
      MDR1 P-glycoprotein, enhances INH accumulation in a manner similar to o-vanadate.
      Verapamil, a calcium channel blocker, also enhances INH uptake. Taken together,
      the results provide evidence of the involvement of both pmf- and ATP-dependent
      extrusion systems in INH efflux in M. smegmatis, making it important to evaluate
      the role of such systems in INH resistance in pathogenic mycobacteria.

PMID- 10080960
TI  - Tyrosine residues of the erythropoietin receptor are dispensable for erythroid
      differentiation of human CD34+ progenitors.
AB  - To study the role of the cytoplasmic domain and particularly the tyrosine
      residues of the erythropoietin receptor (EpoR) in erythroid differentiation of
      human primary stem cells, we infected cord blood-derived CD34+ cells with
      retroviruses encoding chimeric receptors containing the extracellular domain of
      the prolactin receptor (PRLR) and the cytoplasmic domain of either the normal
      EpoR or a truncated EpoR devoid of tyrosine residues. Erythroid differentiation
      of the infected progenitors could thus be studied after stimulation by PRL. The
      complete PRLR was used to assess its ability to substitute for EpoR in erythroid
      differentiation. Typical erythroid day-14 colonies were observed from CD34+ cells
      grown in PRL when infected with any of the three viral constructs. These results
      demonstrate that: (i) the activation of the virally transduced PRLR leads to
      erythroid colony formation showing that erythroid terminal differentiation can be
      induced by a non-erythroid receptor in human progenitors; (ii) a chimeric
      receptor PRLR/EpoR is able to transduce a signal leading to terminal erythroid
      differentiation of human CD34+ cells; (iii) in contrast to results previously
      reported in murine models, tyrosine residues of the EpoR are not required for
      growth and terminal differentiation of human erythroid progenitors.

PMID- 10080961
TI  - Cloning and characterization of a short variant of the corticotropin-releasing
      factor receptor subtype from rat amygdala.
AB  - We have identified and characterized a cDNA encoding a novel isoform of the
      corticotropin-releasing factor (CRF) receptor, referred to as CRF2alpha-tr, from
      the rat amygdala cDNA library. The nucleotide sequence of the cloned cDNA has a
      structure of an alternatively spliced form of the CRF2alpha receptor, which
      contains unspliced introns 6 and 7 in the message, and encodes a 236-amino-acid
      truncated protein that comprises three unique transmembrane domains. Northern
      blot analysis shows that the CRF2alpha-tr receptor is more strongly expressed in
      the rat amygdala, thalamus, and hypothalamus than the intact CRF2alpha receptor.
      Western blot analysis also reveals that the CRF2alpha-tr protein can be expressed
      in transfected COS-7 cells as well as CRF2alpha. Furthermore, this receptor binds
      rat/human CRF with almost the same low affinity (Kd = 12.7 nM) as the CRF2alpha
      and without accumulation of intracellular cAMP. Interestingly, it does not bind
      sauvagine or rat urocortin. These findings suggest that this truncated CRF
      receptor is the major isoform of CRF2alpha receptor mRNA transcripts in the
      amygdala and would mediate some functions of CRF pathways in the central nervous
      system.

PMID- 10080962
TI  - Environmental influences on neural plasticity, the limbic system, emotional
      development and attachment: a review.
AB  - The effects of early environmental influences on neural plasticity, the limbic
      system, and social and emotional development are reviewed and an illustrative
      case study is briefly discussed. Deprived or abnormal rearing conditions induce
      severe disturbance in all aspects of social and emotional functioning, and effect
      the growth and survival of dendrites, axons, synapses, interneurons, neurons, and
      glia. The amygdala, cingulate, and septal nuclei develop at different rates which
      correlate with the emergence of wariness, fear, selective attachments, play
      behavior, and the oral and phallic stages of development. These immature limbic
      nuclei are "experience-expectant," and may be differentially injured depending on
      the age at which they suffer deprivation. The medial amygdala and later the
      cingulate and septal nuclei are the most vulnerable during the first three years
      of life. If denied sufficient stimulation these nuclei may atrophy, develop
      seizure-like activity or maintain or form abnormal synaptic interconnections,
      resulting in social withdrawal, pathological shyness, explosive and inappropriate
      emotionality, and an inability to form normal emotional attachments.

PMID- 10080963
TI  - An adolescent vampire cult in rural America: clinical issues and case study.
AB  - The emergence of cult related activities in rural America are examined. Cults and
      their attraction to adolescents are addressed as are methods of cult
      indoctrination and a profile of cult members and their leader. Clinical
      management along with a rationale for the attraction of some adolescents to cults
      are discussed. A case study of a vampire cult and the psychopathology identified
      in the leader of the cult are provided. Import for clinicians is offered.

PMID- 10080964
TI  - Comparison of Korean-American adoptees and biological children of their adoptive
      parents: a pilot study.
AB  - This study compared a small group of Korean-American adoptees with their adoptive
      siblings who are biological children of the adoptive parents with respect to
      their psychosocial adjustment. Eighteen Korean-American adoptees were compared
      with nine biological children by a structured demographic, medical, clinical
      survey form and the Child Behavior Checklist-Parent Form (CBCL-P). The parents
      did not raise any more concerns about the adjustment of adopted children than
      their biological children. On the CBCL-P, the two groups did not differ
      significantly in competence T-scores, total behavioral problems, broad and T
      scores and the total number of problem behaviors except for lower social
      competence in adopted children and a higher internalization score in biological
      children. In conclusion, the international adoptees, the Korean-American children
      have adjusted well during their early childhood after early adoption. Further
      studies employing a larger sample are warranted to better understand the
      international adoption practice.

PMID- 10080965
TI  - Some risk factors in the psychotherapy of children and families: well-established
      techniques that can put some clients at risk.
AB  - Based on the experience of a sample of professionals who completed a brief
      questionnaire, on the author's own clinical experience, and on a literature
      review cases are presented where selected therapeutic practices in child mental
      health produced negative outcomes and, therefore, place some clients at risk.
      These practices are: empathy, efforts to restructure the family, efforts to
      change disciplinary practices, and structuring for disclosure. In addition, while
      not a process variable, client perceptions of therapy can exacerbate problems.
      Clinicians can use these findings to enhance their consent to treat interactions
      with clients.

PMID- 10080966
TI  - Autistic subjects with comorbid epilepsy: a possible association with viral
      infections.
AB  - This study evaluates the comorbidity of epilepsy as a variable supporting a viral
      hypothesis in Autism. Data covering a 30-year period (1960-1989), including
      general population live births, autistic births, and incidence of viral
      encephalitis and viral meningitis, were collected for Israel. 290 autistic births
      were evaluated. The annual birth pattern of subjects with comorbid epilepsy fit
      the seasonality of viral meningitis. These findings support the role of viral
      C.N.S. infections in the causality of this disorder.

PMID- 10080967
TI  - The psychiatric symptomatology in Kleine-Levin syndrome.
AB  - The Kleine-Levin syndrome is a rare disorder with its main symptoms being
      periodic hypersomnolence and excessive eating accompanied by behavioral changes.
      The dominance of the behavioral and psychological symptoms may obscure the
      diagnosis. In this article the diagnostic process and the psychiatric
      symptomatology of two adolescent male patients with Kleine-Levin syndrome is
      discussed.

PMID- 10080968
TI  - Advances in heart transplantation.

PMID- 10080969
TI  - Advances in pancreas transplantation for the treatment of diabetes.

PMID- 10080970
TI  - Advances in lung transplantation.

PMID- 10080971
TI  - An introduction to plant-cell culture. Pointers to success.

PMID- 10080972
TI  - Callus initiation, maintenance, and shoot induction in rice.

PMID- 10080973
TI  - Callus initiation, maintenance, and shoot induction in potato. Monitoring of
      spontaneous genetic variability in vitro and in vivo.

PMID- 10080974
TI  - Somatic embryogenesis in barley suspension cultures.

PMID- 10080975
TI  - Somatic embryogenesis in Picea suspension cultures.

PMID- 10080976
TI  - Direct cyclic somatic embryogenesis of cassava for mass production purposes.

PMID- 10080977
TI  - Immature inflorescence culture of cereals. A highly responsive system for
      regeneration and transformation.

PMID- 10080978
TI  - Cryopreservation of rice tissue cultures.

PMID- 10080979
TI  - Noncryogenic, long-term germplasm storage.

PMID- 10080980
TI  - Micropropagation of strawberry via axillary shoot proliferation.

PMID- 10080981
TI  - Meristem-tip culture for propagation and virus elimination.

PMID- 10080982
TI  - Clonal propagation of orchids.

PMID- 10080983
TI  - In vitro propagation of succulent plants.

PMID- 10080984
TI  - Micropropagation of flower bulbs. Lily and narcissus.

PMID- 10080985
TI  - Clonal propagation of woody species.

PMID- 10080986
TI  - Spore-derived axenic cultures of ferns as a method of propagation.

PMID- 10080987
TI  - Protoplast isolation, culture, and plant regeneration from Passiflora.

PMID- 10080988
TI  - Isolation, culture, and plant regeneration of suspension-derived protoplasts of
      Lolium.

PMID- 10080989
TI  - Protoplast fusion for symmetric somatic hybrid production in Brassicaceae.

PMID- 10080990
TI  - Production of cybrids in rapeseed (Brassica napus).

PMID- 10080991
TI  - Microprotoplast-mediated chromosome transfer (MMCT) for the direct production of
      monosomic addition lines.

PMID- 10080992
TI  - Guard cell protoplasts. Isolation, culture, and regeneration of plants.

PMID- 10080993
TI  - In vitro fertilization with isolated single gametes.

PMID- 10080994
TI  - Protocols for anther and microspore culture of barley.

PMID- 10080995
TI  - Microspore embryogenesis and in vitro pollen maturation in tobacco.

PMID- 10080996
TI  - Embryo rescue following wide crosses.

PMID- 10080997
TI  - Mutagenesis and the selection of resistant mutants.

PMID- 10080998
TI  - Agrobacterium-mediated transformation of Petunia leaf disks.

PMID- 10080999
TI  - Transformation of rice via PEG-mediated DNA uptake into protoplasts.

PMID- 10081000
TI  - Transformation of wheat via particle bombardment.

PMID- 10081001
TI  - Plant transformation via protoplast electroporation.

PMID- 10081002
TI  - Transformation of maize via tissue electroporation.

PMID- 10081003
TI  - Transformation of maize using silicon carbide whiskers.

PMID- 10081004
TI  - Directing anthraquinone accumulation via manipulation of Morinda suspension
      cultures.

PMID- 10081005
TI  - Alkaloid accumulation in Catharanthus roseus suspension cultures.

PMID- 10081006
TI  - Betalains. Their accumulation and release in vitro.

PMID- 10081007
TI  - Fluorescent measurement of [Ca2+]c. Basic practical considerations.
AB  - Over the last decade the range of fluorescent indicators for Ca2+ has increased
      dramatically so that there are now a host of probes available. Each may offer
      particular advantages depending on the design of the experiment and the
      fluorometric equipment available. Careful choice of the indicator is therefore
      central to achieve a successful outcome. The probe that is chosen will, of
      course, depend on the aims of the experiment, on how the indicator will be
      introduced into the cell(s), and on the excitation source and detection equipment
      that are available. I hope that this chapter will not only help investigators
      choose the most appropriate indicator but, in addition, give an insight into what
      can be achieved using fluorescent Ca2+ indicators.

PMID- 10081008
TI  - Measurement of [Ca2+]i in whole cell suspensions using fura-2.

PMID- 10081009
TI  - Measurement of [Ca2+]i in cell suspensions using indo-1.

PMID- 10081010
TI  - Confocal microscopy. Theory and applications.

PMID- 10081011
TI  - Measurement of intracellular calcium concentration using confocal microscopy.

PMID- 10081012
TI  - Single cell and subcellular measurement of intracellular Ca2+ concentration
      ([Ca2+]i).

PMID- 10081013
TI  - Measurement of [Ca2+] using the Fluorometric Imaging Plate Reader (FLIPR).

PMID- 10081014
TI  - Measurement of Ca2+ entry using 45Ca2+.

PMID- 10081015
TI  - Measurement of [3H]PN200-110 and [125I]omega-conotoxin MVIIA binding.

PMID- 10081016
TI  - Measurement of inositol (poly)phosphate formation using [3H]inositol labeling
      protocols in permeabilized cells.

PMID- 10081017
TI  - Measurement of inositol(1,4,5)trisphosphate using a stereospecific radioreceptor
      mass assay.

PMID- 10081018
TI  - Measurement of calcium fluxes in permeabilized cells using a 45Ca2+ uptake and
      release assay.

PMID- 10081019
TI  - Microinjection of myo-inositol(1,4,5)trisphosphate and other calcium-mobilizing
      agents into intact adherent cells.

PMID- 10081020
TI  - Photolysis of caged calcium using a low-cost flash unit.

PMID- 10081021
TI  - Measurement of Ca2+ flux through Ins(1,4,5)P3 receptor-Ca2+ channels in lipid
      bilayers ("dip-tip" and "Schindler" methodology).

PMID- 10081022
TI  - Continuous fluorescent monitoring of cellular calcium fluxes. A Novell perfusion
      system for the investigation of inosito(1,4,5)trisphosphate-dependent quantal
      calcium release using immobilized, electropermeabilized cells.

PMID- 10081023
TI  - Measurement of free [Ca2+] changes in agonist-sensitive internal stores using
      compartmentalized fluorescent indicators.

PMID- 10081024
TI  - Measurement of [Ca2+]i in smooth muscle strips using front-surface fluorimetry.

PMID- 10081025
TI  - Measurement of calcium and movement in heart cells.

PMID- 10081026
TI  - Simultaneous analysis of intracellular pH and Ca2+ from cell populations.

PMID- 10081027
TI  - Measurement of cytosolic-free Ca2+ in plant tissue.

PMID- 10081028
TI  - Assay and purification of calmodulin-dependent protein kinase.

PMID- 10081029
TI  - Measurement of Ca(2+)-ATPase activity (in PMCA and SERCA1).

PMID- 10081030
TI  - [Progression of chronic renal insufficiency].

PMID- 10081031
TI  - [New target tissues for aldosterone].

PMID- 10081032
TI  - [Fibromuscular dysplasia of the renal arteries].
AB  - Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory vascular
      disease that primary involves medium-sized and small arteries, most commonly the
      renal and carotid arteries. Dysplasic stenoses can be classified by angiography
      into three main subtypes, multifocal (multiple contiguous stenoses with the
      "string of beads" appearance), unifocal (single stenosis in a given renal
      artery), or tubular. The multifocal subtype is the most frequent and is usually
      associated with medial dysplasia, whereas unifocal and tubular stenoses are
      associated with intimal and perimedial dysplasia, respectively. Renovascular
      hypertension, mainly in women aged 30 to 50 years, is the most common
      manifestation of renal artery fibromuscular dysplasia. Its prevalence in
      hypertensive patients is estimated to less than 1 percent. The true prevalence of
      the disease is probably higher, however, because many cases can go undetected in
      normotensive or asymptomatic hypertensive patients. The first line treatment is
      percutaneous transluminal angioplasty that usually allows blood pressure
      improvement or normalization. Stenosis progression is slow and rarely leads to
      ischemic renal failure. Recognition of renal artery fibromuscular dysplasia
      should lead to screening for associated carotid artery lesions. Fibromuscular
      dysplasia can be a familial disease.

PMID- 10081033
TI  - [Factors in the progression of renal insufficiency during the 2 years preceding
      the use of dialysis].
AB  - The respective contribution of sex, type of nephropathy, degree of proteinuria,
      blood pressure, protein and sodium daily intake, lipid profile, protidemia,
      hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure
      progression is debated. The link between these parameters and the decrease of
      creatinine clearance, delta Ccr (according to Cockroft) was assessed in uni and
      multivariate analysis in a population of 49 patients (26 men, 23 women; age 60 +/
      15 years, weight 73 +/- 15 kg) selected out of 173 presently treated
      hemodialysis patients on the basis of availability of a quarterly follow-up for
      two years before starting dialysis. The patients were advised a moderate protein
      and salt restriction which could be retrospectively assessed (on urinary
      excretion of urea and sodium) at respectively 0.82 g/kg/day and 6.5 g/day. The
      two years delta Ccr was 14 +/- 14 ml/min. It was not different in men and women
      (specially when expressed in % of initial value). This decrease in Ccr was
      neither significantly different in glomerular disease (17 +/- 8, n = 14),
      diabetic nephropathy (12 +/- 6, n = 7), nephroangiosclerosis (15 +/- 8, n = 5),
      interstitial nephritis (12 +/- 10, n = 14), and PKD (11 +/- 12, n = 9). Patients
      with antihypertensive drugs (n = 42) had a faster progression than those without
      drugs (n = 7): delta Ccr = 15 +/- 14 vs 7 +/- 7 ml/min (p < 0.05) in spite of
      comparable blood pressure but with higher proteinuria. Linear regression of delta
      Ccr with the initial and two year averaged values of the quantitative parameters
      showed a significant positive link for both values with cholesterol, hemoglobin
      and proteinuria and a negative one with protidemia. A positive link was observed
      with the initial value of bicarbonate and the two year mean of diastolic and mean
      blood pressures. No link at all was observed with urea and Na excretion, CaPO4
      product and triglycerides. Multiple regression disclosed a significant link only
      for protidemia (negative with both initial and two years averaged value),
      diastolic BP (only for the two year averaged value and hemoglobinemia (for the
      initial value). When the patients were classified according to a threshold value
      of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the
      combination of two risk factors of progression (pro-tidemia < 66 g/l, DBP > or =
      90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > 3g/d, CT > 5 mmol/l) had a
      significantly greater decrease of Ccr than those with the three other
      combinations at the exception of the association of low protidemia with DBP.
      CONCLUSION: 1. diastolic hypertension and low protidemia are the two most
      important factors predicting progression of renal failure; 2. a predictive
      synergy was furthermore pointed out between on one hand low protidemia and
      diastolic hypertension and on the other hand proteinuria and cholesterol; 3. on
      the contrary, anemia attenuates progression linked to low protidemia, diastolic
      hypertension, proteinuria and high cholesterol.

PMID- 10081034
TI  - [Data collection about the case management of end-stage renal insufficiency.
      Feasibility study. Nephrology Epidemiologic and information Network (REIN)].
AB  - End-stage renal failure (ESRD) is an important public health issue, because of
      both the increasing number of patients requiring renal replacement therapy and
      the cost of treatment. The need for a reliable data system, capable of describing
      the patient care network as a whole, including dialysis or transplantation, has
      often been reiterated. The Direction Generale de la Sante (the French Department
      of Health) commissioned INSERM (the National Institute of Health and Medical
      Research) to "study the feasibility of different scenarios of data collection
      about ESRD patient care in order to meet the priority needs of health care
      administration, physicians, and researchers". Analysis of these needs allowed the
      goals to be defined: to provide an accurate picture of ESRD patient care in order
      to guide and evaluate health care policy, to inform clinicians, and to provide a
      tool for more focused special studies in renal research issues. Three scenarios
      were studied: the first would use data systems of both the government and the
      National Health Insurance system for planning health care services, upon EfG (The
      French Transplant Agency) network to evaluate transplantation, and upon a few
      regional registries for epidemiology and research; the second is based on
      repeated cross-sectional surveys; the third would rely upon the organization of
      an information system, the Renal Epidemiology and Information Network (REIN).
      Regional centers and a national coordinating office would register and follow-up
      ESRD patients, principally to evaluate health care supply and quality. The REIN
      database would also be a resource for research. The advantage of the first
      scenario is its low cost; its principal drawback is that evaluations will not be
      possible in the regions without registries. The second suggestion is inadequate.
      The last project would fulfil the goals that were defined. The REIN data system
      would be a true public health project of interest to all the participants and
      institutions in this field.

PMID- 10081035
TI  - [Fenofibrate increases blood creatinine, but does not change the glomerular
      filtration rate in patients with mild renal insufficiency].
AB  - Fenofibrate is a potent hypolipemic agent, widely used in patients with mild to
      severe renal failure in whom hyperlipoproteinemia is frequent. A moderate
      reversible increase in creatinine plasma levels has been reported with
      fenofibrate therapy; however, it is not known whether this increased
      creatininemia reflects a fenofibrate induced alteration of renal function or if
      fenofibrate interferes with creatinine tubular handling. We prospectively
      examined the effect of 2 weeks fenofibrate treatment (200 mg daily) on renal
      function in thirteen hyperlipidemic patients with normal renal function or mild
      to moderate renal failure (Creat Cl: 110 to 30 ml/min). This study confirms that
      fenofibrate therapy significantly increases creatininemia in patients with mild
      to moderate renal failure (147 +/- 12 versus 170 +/- 15 mmol/l; p = 0.014), but
      does not alter renal hemodynamic nor glomerular filtration rate as assessed by
      the stability of PAH (304 +/- 56 versus 311 +/- 49 ml/min; p = NS) and inulin
      clearances (51.7 +/- 6 versus 52.3 +/- 7 ml/min; p = NS). The increase in
      creatininemia is neither due to an inhibition of creatinine tubular excretion,
      since no change in creatinine clearance was observed (69 +/- 8 versus 68 +/- 8
      ml/min; p = NS), but appears to be associated to a parallel increase in
      creatinine daily urinary excretion (13.7 +/- 5 versus 15.4 +/- 4 mmol; p = 0.03).
      In conclusion, fenofibrate therapy in renal patients does not worsen renal
      function, nor diminish the reliability of creatinine clearance for its follow-up
      in spite of a significant rise in creatininemia. The mechanism of the fenofibrate
      induced increase in urinary creatinine excretion remains to be determined.

PMID- 10081036
TI  - [Time-tested methods--improved by innovations... The journal "Der Orthopade"
      introduces new original concepts].

PMID- 10081037
TI  - [Hyalin substance--is it irreparable...?].

PMID- 10081038
TI  - [Indication for and performance of articular cartilage drilling using the Pridie
      method].
AB  - Articular cartilage has only a small capacity for regneration. This makes the
      repair of articular surfaces difficult. In 1959 Pridie described his method of
      resurfacing osteoarthritic knee joints. This operation is still in widespread use
      today. Pridie introduced the principle of drilling exposed subchondral bone with
      the objective of encouraging a fibro-cartilaginous repair. The newly formed
      fibrocartilaginous layer that develops over the lesion in osteoarthritis may be
      enough to decrease patients symptoms. Bone drilling into the subchondral layer is
      also effective in promoting healing of osteochondrosis dissecans. The choice of
      the treatment should be based on factors such as age of the patient, serverity of
      symptoms, activity level and functional demands on the joint, site and stage of
      the lesion. The drilling operation remains useful in osteoathritis and
      osteochondrosis dissecans.

PMID- 10081039
TI  - [Abrasion arthroplasty].
AB  - The removal of areas of chondromatous hyaline cartilage and the attempt to create
      new lod capacities for articular surfaces remain an encore in miscellaneous
      variations, pursued over decades in the last century. Recent research findings
      describe the biochemical interrelations and the three-dimensional structures of
      the collagenic matrix much more exactly. It was not until now a better insight
      into the metabolism and the dependent "state of aggregation" of the cartilage
      under changing mechanical exertion was made possible. From it prove, that the
      hyaline cartilage of the articulations represent a highly differentiated
      structure that is susceptible to mechanical and metabolic noxa and avails of
      remarkably minimal capability of regeneration. The results of repair are not
      within reach to approximate to functional ability of the original. This lights up
      that the amititious beginning to get to qualitative comparable regeneration by
      repair is not completed yet. Previous and furthermore differentiated and with
      restrictions of chondrocytes in compound with other protective and stimulating
      substances. Hitherto it seems advisable to refrain from steps being too active
      therapeutically. The unadulterated open abrasion of pathological articular
      cartilage has to be marked obsolete, today. Also the effect of abrasive
      arthroplasty, inductive character suggested, remains in the opinion of well-known
      authors in no proportion to expenditure of operation and rehabilitation and the
      expenses, because a sustaining success is not be expected in the long run, no
      matter whether drilling is done merely subcortical or subchondral, or use of
      spongiosa or microfracturing procedures. A more positive perspective in therapy
      appears with the holmium YAG-laser paving the way for gently treatment merely for
      degenerated cartilage: Regenerative beginnings to build hyaline cartilage have
      been reported. The abrasive arthroplasty probably will establish as a joint
      conserving procedure in combination with the possibility of transplantation of
      chondrocyxtes to improve specific construction of the collagen matrix.

PMID- 10081040
TI  - [Autologous osteo-chondral grafts in the management of articular cartilage
      lesions].
AB  - It is well known that the capacity of articular cartilage for repair is limited.
      There have been many attempts to address this problem. However, treatment options
      are limited and the long-term outcome is uncertain. This article will focus on
      the osteochondral autograft transplantation (OAT), which is currently the only
      surgical cartilage repair technique that provides and retains proper hyaline
      articular cartilage. Osteochondral autograft transplants have been associated
      with a good rate of success, but further long-term follow-up and biomechanical
      evaluation are essential. LIMITATIONS: size and depth of osteochondral defects,
      availability of donor autologous grafts, potential for damaging donor sites, the
      dead spaces between circular grafts and integration of donor and recipient
      hyaline cartilage.

PMID- 10081041
TI  - [The microfracture technic in the management of complete cartilage defects in the
      knee joint].
AB  - Full thickness defects of the articular cartilage rarely heal spontaneously.
      While some patients do not develop clinically significant problems from chondral
      defects, most eventually develop degenerative changes associated with the
      cartilage damage over time. Techniques to treat chondral defects include
      abrasion, drilling, tissue autografts, allografts, and cell transplantation. The
      senior author has developed a procedure referred to as the "microfracture." This
      technique enhances chondral resurfacing by providing a suitable environment for
      tissue regeneration and by taking advantage of the body's own healing potential.
      This technique has now been used in more than 1400 patients. Specially designed
      awls are used to make multiple perforations, or "microfractures", into the
      subchondral bone plate. The perforations are made as close together as necessary,
      but not so close that one breaks into another. Consequently, the microfracture
      holes are approximately three to four millimeters apart (or 3 to 4 holes per
      square centimeter). Importantly, the integrity of the subchondral bone plate is
      maintained. The released marrow elements form a "super clot" which provides an
      enriched environment for tissue regeneration. Follow up with long term results of
      more than 8 years have been positive and very encouraging.

PMID- 10081042
TI  - [Autologous osteochondral transplantation on various joints].
AB  - A chondral/osteochondral defect involving the articular surface of a joint is
      still a therapeutic problem. The goal of articular cartilage repair is
      restoration of cartilage congruity, accomplishing full painfree range of motion
      and elimination of cartilage detoriation. The use of autologous grafts was first
      reported by Wagner 1964. Now the use of cylindrical autograft plugs was described
      by Bobic 1996 and Hangody 1996. Operative management and early results of
      osteochondral cylindrical autograft plugs in the femoral condyle, patella, elbow
      and talar dome are presented. The arthroscopic/open use of autologous
      osteochondral grafts from the knee is indicated in osteochondral lesions in
      diameter from 1 to 3 cm, which can not be primarily refixed and in osteonecrosis
      at femoral condyle, patella, elbow, talar dome as well as shoulder.

PMID- 10081043
TI  - [Transfer of the posterior femoral condyle. First experience with a salvage
      operation].
AB  - In this study large osteochondral defects on the weight-bearing surface of the
      medial and lateral femoral condyle were treated by transplantation of the
      autologous posterior condyle in 20 patients. The cartilage defects, type
      Outerbridge IV, ranged in size from 2 x 1.5 cm to 5 x 3.5 cm. 8 condyle transfers
      were done from 1984-1996 at the orthopaedic clinic of the university of Balgrist,
      Zurich. 12 condyle transfers at the department of orthopedic sports medicine at
      the technical university of Munich from 1996-1998. Patients were operated before
      the condyle transfer, 2 times on average. In 9 patients a high tibial osteotomy
      was performed simultaneously. Clinical evaluation was done according to the
      Lysholm score. The Lysholm score improved in the patient serie from 1996 from
      preoperatively 62 (54-81) points to postoperatively 85 (74-95) points. The follow
      up was on average 9.8 (2-26) months. 18 patients reported about pain relief, 2
      patients didn't improve. We describe the operative technique. Despite the lack of
      long-term results the transfer of the autologous posterior condyle seems to be an
      effective alternative for the knee prosthesis, especially for young patients with
      a great cartilage damage in the weight bearing area.

PMID- 10081044
TI  - [Transplantation of chondrogenic tissue in the treatment of lesions of of the
      articular cartilage].
AB  - The problem in the treatment of deep hyalin cartilage defects is due to the
      minimal regeneration potential of this specific tissue. Several attempts were
      made to solve this difficulties experimentally and clinically. The proliferative
      potential of autogenous perichondrium/periost is well-known for decades.
      Perichondrium can be harvested from the lower ribs near to the sternum and
      periost from the adjacent bone (mostly proximal tibia). Experimentally and
      clinically, it has been shown that both types of tissue bear the potential to
      form hyalin-like cartilage under in vitro and in vivo conditions. Furthermore,
      regarding the biomechanical data (shear modulus) and the biochemical data
      (content of type II collagen) the newly grown tissue resembles normal hyalin
      cartilage. In addition, it has been shown that the transplant fixation with
      fibrin glue is sufficient in order to allow early postoperative treatment with
      continuous passive motion which is known to stimulate cartilaginuous
      regeneration. Despite the satisfying experimental and clinical results further
      examinations are needed in order to evaluate the optimal surgical technique and
      postoperative regimen regarding the CPM-criteria. In addition, application of
      growth-factor might further improve this biological kind of treatment which has
      to be analysed.

PMID- 10081045
TI  - [Cartilage replacement operation using pre-cultured cells].
AB  - Clinical results using transplantation of precultivated autologous chondrocytes
      for treatment of circumscribed chondral injuries in the knee joint have been
      presented 1994. The quality of this method for clinical use can not be evaluated
      at the moment since controlled randomized trials comparing this method with bone
      drilling, use of periostal flaps or conservative treatment do not exist.
      According to recent experimental results, techniques using precultivated cells,
      growth factors and different scaffolds for repair of limited cartilage defects
      are not satisfactory yet, and it is unproven whether these methods are superior
      to simple bone-drilling. Use of precultivated cells and growth factors might
      nevertheless have a potential in the future, when we have learned to use them
      under optimized conditions. Unless these conditions have been developed and
      proven to reliably improve cartilage repair above previous methods, in a clinical
      case the treatment should be chosen which is the least invasive.

PMID- 10081046
TI  - [Growth behavior of chondrocytes on various biomaterials].
AB  - Chondrocytes can be cultured on different three-dimensional culture systems
      suitable for transplantation to enhance the repair of localized cartilage
      defects. Articular cartilage chondrocytes from adult rabbit knees and from bovine
      calf metacarpophalangeal joints were isolated by enzymatic digestion and cultured
      in a monolayer system to amplify cell count. After amplification the cells were
      seeded on different biocompatible materials. We investigated two types of
      bioresorbable polymer fleece matrices (a composite fleece of polydioxanon and
      polyglactin and a resorbable poly-L-lactic acid fleece) and lyophilized dura as a
      biological carrier. On all three types of transport media the phenotypic and
      morphological appearance of cultured chondrocytes could be observed. The
      production of glycosaminoglycans was revealed by Alcian blue staining and
      immunohistochemical detection of Chondroitin-4 and 6-sulfate in the created
      constructs. The material properties of the carriers allow for transplantation of
      the artificial cartilage-like products into full thickness articular cartilage
      defects and could therefore improve the minor intrinsic healing capacity of
      cartilage tissue. Bioartificial cartilage may become a future perspective in the
      treatment options of orthopaedic and plastic surgery.

PMID- 10081047
TI  - [Gene transfer in the treatment of arthritis].
AB  - Current concepts in treating arthritis by gene transfer are described, including
      different vector systems and strategies of gene transfer into target cells.
      Promissing antiarthritic gene products are a variety of growth factors which
      facilitate increased matrix synthesis and mitogensis in articular chondrocytes.
      Furthermore, rheumatoid joint destruction can be treated genetically by the
      transfer of certain antiinflammatory cytokine genes, which provide locally high
      concentrations of the antiinflammatory gene product. First clinical trails using
      the IRAP gene (interleukin I receptor antagonist protein) to eliminate the
      inflammatory reaction caused by interleukin I in rheumatoid joints are on its
      way. In order to investigate potential improvement in cartilage regeneration
      retroviral TGF-beta gene transfer in rabbit articular chondrocytes has been
      carried out. The TGF-beta group showed an in vitro increase in collagen type II
      neosynthesis by 304%, compared to normal chondrocytes.

PMID- 10081048
TI  - [Management of Achilles tendon rupture].

PMID- 10081049
TI  - Hockey.
AB  - Hockey is a game of strength, speed, and skill. It is among the most difficult to
      master, the costliest to equip, the fastest to watch, and the most dangerous to
      play. It requires a combination of power, endurance, and flexibility applied
      within a confined space over a cold, hard, and slippery surface. It is a game of
      control and lack of control, both of emotions and flying objects. Hopefully, the
      reader will be better suited to understand the "culture" of hockey, both
      clinically and functionally, and can better interact with the men and women who
      play this fantastic sport, the one I hope to be playing for another 25 years, or
      until I finally get it right!

PMID- 10081050
TI  - Volleyball.
AB  - Volleyball has become one of the world's most popular participatory sports in
      recent years. There are many dynamic skills and movements needed to play the
      game. As a result, many overuse and traumatic injuries to the extremities and
      back may occur. This article addresses the history of the sport and its
      terminology. Common injuries and rehabilitation recommendations are also
      discussed.

PMID- 10081051
TI  - Martial arts.
AB  - The martial arts have a reputation for being a high-risk activity, but are
      generally practiced in a safe environment. This article presents the results of a
      survey which is used to calculate risk of injury per 1000 hours of practice. The
      injury rate compares favorably with other mainstream activities; in fact, the
      martial arts are generally considered safer than most. The most common injuries
      occur to the wrist, hand, finger, foot, knee, head, and thigh. Special issues of
      importance for prevention and treatment of these injuries are discussed.

PMID- 10081052
TI  - Sports medicine and sailing.
AB  - Although there is little epidemiologic data in the sport of sailing, the
      identification of important trends can assist the clinician in successful
      evaluation, treatment, and rehabilitation of the individual. It appears that like
      other sports, the majority of injuries encountered are of the microtraumatic or
      overuse type. An understanding of biomechanics, the overload injury, and the
      sport of sailing will allow the development of a comprehensive rehabilitation
      program to ensure the optimal performance and safety of the sailor.

PMID- 10081053
TI  - Bicycling injuries.
AB  - The severity of injuries secondary to bicycling range from the pain and nuisance
      of skin abrasions to life-threatening brain injuries. For most injuries, the key
      to treatment and prevention is careful assessment of bike fit and training
      techniques. In general, the treatment of musculoskeletal and neuropathic lesions
      should follow sound, physiatric treatment principles. Clearly, all clinicians who
      treat bicyclists have a professional responsibility to educate them on the use of
      helmets and safe riding rules.

PMID- 10081054
TI  - Swimming overuse injuries.
AB  - Swimming injuries are unique in that they involve upper limb overuse more than
      lower limbs and that swimming is performed in a non-weight-bearing fluid setting.
      Identifying the mechanism of injury and prescribing appropriate management is not
      easy unless one has a thorough understanding of proper technique of the four
      competitive strokes. Understanding the psychology of swimming athletes will
      improve outcome and compliance. The goals of this article are to familiarize the
      reader with the diagnosis and management of swimming injuries and to improve the
      physician's effectiveness in dealing with swimmers through a thorough
      understanding of technique and psychology.

PMID- 10081055
TI  - Football injuries.
AB  - Players of football will suffer injury. These injuries with their potential
      effects on the rest of the athlete's lives should be treated with aggressive
      recognition and rehabilitation of acute injuries. Care should be taken when
      interpreting published data on football injuries, as the definition of "injury"
      may widely vary. The most effective treatment of any of the injuries reviewed is
      prevention. Preseason conditioning, attention to safe technique, and appropriate
      use of equipment are key preventive strategies. Recently the seriousness of even
      mild traumatic brain injury (and the second impact syndrome) has reached national
      consensus. Return to play decisions will be executed most effectively if a clear
      plan for handling these situations is in place before the injuries take place.
      Overall, sports medicine research and education have significantly reduced the
      frequency and seriousness of injuries suffered during football.

PMID- 10081056
TI  - Wrestling.
AB  - Wrestling is considered one of the most physically demanding sports among high
      school and college athletics and, as such, has a proportionate number of
      injuries. Strength and endurance is paramount to successful performance. The
      wrestler needs to have not only strength and endurance, but also technical skill
      to be successful. Weight control and weight loss distinguish it from most other
      sports at the high school and collegiate levels. In addition to musculoskeletal
      problems, medical conditions and diseases impact the ability if the wrestler is
      to safely participate in this demanding but rewarding sport.

PMID- 10081057
TI  - Baseball/lacrosse injuries.
AB  - With the expansion of baseball into all age groups, the game is becoming as much
      a recreational sport as a youth sport. Throwing arm injuries eventually limit the
      participation of most players. Analysis is made of these injuries with the goal
      of complete rehabilitation for the baseball player. Lacrosse has also seen an
      increase in popularity as a recreational sport. Analysis of lacrosse injuries and
      rehabilitation of the most common injuries is reviewed.

PMID- 10081058
TI  - Rugby football.
AB  - Rugby union football continues to gain in popularity in the United States. Both
      men's and women's clubs have been established at several colleges and
      universities. There has been substantial growth in the number of high school
      rugby football clubs in recent years. With the increase in numbers of young
      participants in this sport, it is important that great efforts be mounted to
      attempt to control the injury rates and severity of injuries in rugby football.
      Players and coaches must be knowledgeable of the rules of the game, and referees
      must strictly enforce these rules. Physicians and dentists should be involved in
      educating parents, coaches, players, and school officials about the inherent
      risks of injury and the means for injury prevention. Medical personnel must also
      be instrumental in educating players about alcohol abuse/addiction. Rugby players
      should be encouraged to use the limited protective gear that is allowed: wraps,
      tape, joint sleeves, scrum caps, and facial grease to prevent lacerations.
      Mouthguards are strongly recommended at any level of play and should be mandated.
      The use of helmets, face masks, and shoulder pads has been suggested by some
      authors. Such rule changes could actually increase injury rates and severity,
      because this equipment could be used as weapons as they are in American football.
      It is recommended that rugby clubs purchase or build equipment to practice
      scrummage skills. Coaches should be experienced and attend clinics or complete
      video courses on medical emergencies and safe techniques of the game. Injury
      frequency and severity can be decreased by adequate preseason training and
      conditioning, proper tackling and falling techniques, strengthening of neck
      muscles, and allowing only experienced, fit athletes to play in the front row.
      Medical surveillance must be improved at matches and, ideally, at practice
      sessions. At present, it is common for no emergency medical personnel or
      physicians to be present at matches in the United States. Better case registers
      are necessary to monitor rugby injuries, but more medical professionals must
      become involved in the sport to obtain useful data. Rugby players will respect
      the advice of a medical adviser, providing he or she is knowledgeable. This is a
      hardy group of athletes with a cavalier attitude, as evidenced by the injury
      statistics and the case studies above. Their sport can be made safer without
      diminishing the intensity of the game or the camaraderie the players enjoy.

PMID- 10081059
TI  - Figure skating injuries.
AB  - Figure skaters who train regularly sustain primarily lower extremity injuries,
      especially overuse injuries. Quadriceps and hamstring stretching may help prevent
      or decrease anterior knee pain. Foot and ankle problems may be related to the
      rigidity of the leather skating boot. The need for trunk strength to maintain
      body position is frequently under-emphasized. Air quality may also be a problem
      for those who skate in enclosed rinks.

PMID- 10081060
TI  - Snow skiing.
AB  - There are many inherent difficulties in the collection of epidemiologic ski data,
      but important trends have been identified. Further investigation into
      controllable risk factors is currently in progress in an attempt to reduce injury
      incidence, along with prophylactic strength training and conditioning programs. A
      comprehensive ski-specific training program entailing training of the energy
      systems, isolated and kinetic chain strength training, skill-specific training,
      and psychological training is essential to ensure the optimal performance and
      safety of the skier. Rehabilitation issues also can be addressed in the context
      of the above elements.

PMID- 10081061
TI  - Athletes with disabilities.
AB  - Sports participation by persons with disabilities has increased dramatically over
      the past fifty years. Athletes with spinal injury, amputees, and those with
      developmental disabilities are at risk for certain injuries because of their
      specific injury impairments. There are also general medical problems that can
      arise in association with these physical conditions. Providing sporting event
      coverage and appropriate treatment for the disabled athlete requires knowledge of
      these impairment-specific injuries and risks. Physiatrists can provide essential
      leadership and and support to disabled sports programs.

PMID- 10081062
TI  - Rho family proteins and regulation of the actin cytoskeleton.

PMID- 10081063
TI  - Regulation of cytoskeleton and cell adhesion by Rho targets.

PMID- 10081064
TI  - Rnd proteins: a new family of Rho-related proteins that interfere with the
      assembly of filamentous actin structures and cell adhesion.

PMID- 10081065
TI  - The DH protein family, exchange factors for Rho-like GTPases.

PMID- 10081066
TI  - RhoGAPs and RhoGDIs, (His)stories of two families.

PMID- 10081067
TI  - Roles of PAK family kinases.

PMID- 10081068
TI  - Rac and Cdc42 effectors.

PMID- 10081069
TI  - Small GTPases of the Rho family and cell transformation.

PMID- 10081070
TI  - Rho GTP-binding proteins as targets for microbial pathogens.

PMID- 10081071
TI  - Rho GTPases in development.
AB  - It is becoming increasingly clear that the complex family of Rho-related GTPases
      and their associated regulators and targets are essential mediators of a variety
      of morphogenetic events required for normal development of multicellular
      organisms. It is worth noting that the results obtained thus far indicate that
      the Rho family proteins are largely associated with the regulation of
      morphogenesis, as opposed to other essential developmental processes such as cell
      proliferation and cell fate determination. Accumulating evidence also suggests
      that the role of these proteins and their associated signaling pathways in
      morphogenesis is in many, but not necessarily all, cases related to their ability
      to affect the organization of the actin cytoskeleton. Thus, these in vivo
      observations have served to corroborate similar findings in numerous cultured
      cell studies. As described, the power of genetics, particularly in Drosophila and
      C. elegans, has been critical to the recent identification and functional
      characterization of several Rho family signaling components. Moreover, evidence
      suggests that the highly evolutionarily conserved structures of many of these
      proteins translate into conservation of function as well. Thus, it will be
      possible, in many cases, to extrapolate the findings in the simple systems
      described herein to higher eukaryotes, including humans. Expanding use of these
      genetic model systems to dissect Rho-mediated signaling pathways in vivo will
      undoubtedly lead to a flood of new insights into the organization and function of
      these pathways in the coming years, especially in development. As the C. elegans
      genome sequencing effort nears completion and with the Drosophila genome project
      well underway, the identification of novel relevant genes will proceed with even
      greater speed. In addition, the rapidly expanding use of mouse knockout
      strategies, combined with recent developments in the associated knockout
      technology, will also contribute greatly to the investigation of mammalain Rho
      signaling pathways and their roles in development.

PMID- 10081072
TI  - [Nutrition and nutritional behavior].

PMID- 10081073
TI  - [Food preferences of 10- to 14-year-old boys and girls].
AB  - To assess their food preferences a list of 114 foods and 14 beverages was
      submitted to a sample of 696 boys and 537 girls aged 10 to 14 years. For each
      item subjects had to rare by means of a five-point facial scale how much they
      liked or disliked it. Items with highest preference ratings were foods like
      pizza, ice cream, spaghetti, French fries, hamburgers, pudding, corn flakes,
      potato chips and popcorn, but also included the most common types of fruit.
      Disliked to a high degree were liver, canned or steamed fish, raw sauerkraut and
      red cabbage. In food groups derived by factor analysis, fast food, candy and
      salty snacks (along with fruit) showed highest mean liking, while vegetables
      (particularly cooked) ranked at the bottom of the scale. In boys significantly
      stronger preferences were found for food groups such as fast food, meats, cold
      cuts and fish, whereas girls had a (slightly) higher preference for fruit,
      vegetables and cheese. Neither children's age nor relative weight were related to
      their food preferences to a significant degree. Similarly, groups defined by
      father's educational level did not show important differences in their food
      preferences.

PMID- 10081074
TI  - [Attitude to eating and body weight by 11- to 16-year-old adolescents].
AB  - Based on the data of 966 students grade five to eight, a new questionnaire--the
      "Eating Behaviour and Weight Problems Inventory for Children (EWI-C)"--was
      developed. Its 60 items are assigned to 10 subscales measuring: (1) hunger level
      and susceptibility to food cues, (2) importance and impact of eating on sense of
      well-being, (3) eating as a means of coping with emotional stress, (4) concerns
      about eating and weight, (5) dietary restraint, (6) attitude toward healthful
      nutrition, (7) attitude toward the obese, (8) pressures to eat from parents, (9)
      fear of weight gain, (10) figure dissatisfaction. Neither children's age nor
      father's educational level were related to their subscale scores to a significant
      degree. However, on all scales (except scale 3) important gender differences
      could be observed. From the youngest age groups on, mean values of girls clearly
      exceeded those of boys on scales 4, 5, 9 and 10, while on scales 1, 2, 7 and 8
      mean scores of girls were significantly lower. To analyse relationships between
      EWI scores and children's relative weight, 620 students' data were combined with
      those of 445 adolescents attending weight-reduction programs in two obesity
      clinics. Boys' and girls' individual deviations from mean weight per height were
      used to form six groups ranging from underweight to severe obesity. In both sexes
      mean scores on scales 3-5, 9 and 10 significantly increased with increasing
      (over) weight, while a (partial) decrease could be observed on scales 2 and 8.
      Scores of subscales 1 and 7 proved to be independent of children's relative
      weight. Based on the data of the combined sample (n = 1065), norm tables with
      percentile ranks are provided which allow for children's sex and weight. By means
      of these tables the position of a boy's or girl's subscale score can be evaluated
      in relation to his/her weight category (underweight, normal weight, obesity,
      severe obesity). A child's responses on the EWI-C can be analysed by a DOS
      program which is available on diskette.

PMID- 10081075
TI  - The flavor of life: perinatal development of odor and taste preferences.
AB  - Despite the importance of chemosensation in the regulation of ingestive behavior,
      we still know surprisingly little about the development of the olfactory,
      trigeminal and gustatory systems. All three, however, are functional to some
      degree prenatally, and by birth infants are able to respond to a wide range of
      odors and can clearly distinguish between the tastes of sweet, sour and bitter.
      Based on findings from our work in the rabbit, we report that learning of odors
      associated with the mother's diet can occur very early in development, even
      prenatally, that it can have a long-term influence on later food choice, and may
      even lead to enhanced, stimulus-specific sensitivity of the basic sensory
      apparatus. Whether comparable phenomena exist in human infants is not known,
      although our recent findings that nationalities differ in judgements of the
      pleasantness of food odors depending on whether these are recognized as
      representing familiar, culture-typical foods, suggests that it might. A cross
      cultural study is currently in progress examining the influence of culture
      specific childhood eating experiences on adult preferences for food-associated
      odors.

PMID- 10081076
TI  - The control of appetite: basic concepts and practical implications.
AB  - Over the last decade physiological mechanisms have been revealed which have
      increased our understanding of the role of biology in controlling energy balance
      through processes of inhibition and termination of eating. However, in the
      majority of cases, these mechanisms do not constitute a biological imperative.
      The expression of appetite remains dependent upon an interaction between biology
      and the environment [4] and, at the present time, the environment contains
      extremely potent factors which for many people (adults and children) can readily
      overcome biological processes operating to maintain body weight.

PMID- 10081077
TI  - The long-term outcome of retarded fetal growth.
AB  - Recent findings suggest that many human fetuses have to adapt to a limited supply
      of nutrients and in doing so they permanently change their physiology and
      metabolism. These "programmed" changes may be the origins of a number of diseases
      in later life, including coronary heart disease and the related disorders stroke,
      diabetes and hypertension.

PMID- 10081078
TI  - [The worm clarified the findings].

PMID- 10081079
TI  - Evolution of the delta F508 CFTR mutation.

PMID- 10081080
TI  - Killing vs suicide in antibacterial defence.

PMID- 10081081
TI  - Signs and portents: molecular signals and infectious diseases.

PMID- 10081082
TI  - CpG DNA: a novel immunomodulator.

PMID- 10081083
TI  - Macrophages in host defense against Histoplasma capsulatum.
AB  - Macrophages function in both innate and cell-mediated immunity in host defense
      against pathogenic fungi. They initially serve as a protected environment in
      which the primary fungal pathogen Histoplasma capsulatum multiplies and
      disseminates from the lung to other organs. Upon induction of cell-mediated
      immunity, cytokines activate macrophages to destroy the yeasts and thus remove
      them from the host.

PMID- 10081084
TI  - Recognition and receptors in virus transmission by arthropods.
AB  - Fundamental knowledge of the molecular mechanisms underlying virus transmission
      by arthropods is a prerequisite for the creation of new strategies to modulate
      vector competence. There have been several recent advances in identifying the
      viral and vector determinants involved in virus recognition, attachment and
      retention.

PMID- 10081085
TI  - Intracellular determinants of picornavirus replication.
AB  - Viruses replicate in a restricted number of hosts and tissues. In addition to
      viral receptors, several intracellular factors can be involved in determining
      tissue tropism. Many proteins have recently been implicated in picornavirus
      translation and RNA replication. Although the functional role of these proteins
      has not been established in vivo, it is possible that they determine cell-type
      tropism and the pathogenic outcome of the infection.

PMID- 10081086
TI  - Recent advances in identifying and validating drug targets in trypanosomes and
      leishmanias.
AB  - The unique aspects of the biochemistry of trypanosomatids make rational drug
      design an attractive approach, but targets must be selected carefully. Genetic
      manipulation provides a valuable means of mimicking loss of function attributable
      to therapeutic intervention, but caution must be exercised when interpreting such
      data with respect to target validation.

PMID- 10081087
TI  - Proteasomes and other self-compartmentalizing proteases in prokaryotes.
AB  - The proteasome represents the major non-lysosomal proteolytic system in
      eukaryotes. It confines proteolytic activity to an inner compartment that is
      accessible to unfolded proteins only. The strategy of controlling intracellular
      breakdown of proteins by self-compartmentalization is also used by different
      types of prokaryotic energy-dependent proteases. Genomic sequencing data reveal
      that various combinations of these energy-dependent proteases occur in
      prokaryotic cells from different lineages.

PMID- 10081088
TI  - [Ultrastructural study of specialized conducting and working myocytes in the
      sinoatrial region of the human heart. I. Qualitative analysis].
AB  - A qualitative ultrastructural analysis of specialized conducting and working
      myocytes in the sinoatrial region of the human heart was made using autopsied and
      biopsied material from 45 men and women. Autopsied material was prepared not
      later as than 3 hours after the death. Biopsied material was taken during the
      operation for surgical correction of disturbances of cardiac rhythm and
      conduction. Cell contacts of light and dark myocytes within the sinus node, and
      of working myocytes of the right atrium were evaluated. The ratio of light to
      dark myocytes in the sinus node were estimated from both dead people and
      patients. The principles of correct ultrastructural classification of conducting
      and working myocytes in human heart are discussed.

PMID- 10081089
TI  - [DNA-dependent RNA polymerase I from human placental nuclei].
AB  - This paper describes a large-scale method for solubilisation and purification of
      DNA-dependent RNA-Polymerase I from mature human placenta. The solubilisation
      method involves homogenization of the whole human placenta, isolation of cell
      nuclei, sonication of separated nuclei at high ionic strength and ammonium
      sulfate precipitation. The purification method consists of chromatography of RNA
      Polymerase I activity on DEAE-Sephadex A-25 and Phosphocellulose P-11, and
      glycerol-density gradient centrifugation. In result, RNA-Polymerase I of human
      placenta nuclei has been shown to be completely resistant to alpha-amanitin.
      Besides dependence of RNA-Polymerase I on different Mg2+ and Mn2+ concentrations,
      glycerol concentration and ionic strength was studied. Using our results, an
      optimal RNA-Polymerase I assay mixture was developed. The subunit composition of
      RNA-Polymerase I was investigated by dodecylsulfate-gel electrophoresis. The RNA
      Polymerase I molecule of human placenta consists of 13-14 polypeptides.

PMID- 10081090
TI  - [EGF-dependent association of 20S-proteasome and alpha-RNP particles with the
      epidermal growth factor receptor in A-431 cells].
AB  - Here we demonstrate that the epidermal growth factor (EGF) induces association of
      prosomes (20S-proteasomes) with its receptor in A-431 cells. Additionally, ligand
      dependent association of ribonucleoprotein particles (alpha-RNP), containing
      small ALU-like RNA, with the EGF receptor was demonstrated. A suggestion has been
      put forward on the involvement of prosomes and alpha-RNP in the EGF signal
      transmission to different stages of gene expression.

PMID- 10081091
TI  - [EGF-dependent epithelial cells of the mammary cell line HC11 demonstrate a high
      degree of synchronized cell cycle during stimulation with epidermal growth
      factor].
AB  - The most popular object for studying endocytosis of EGF-receptor complexes, human
      epidermoid carcinoma A431, was shown to answer to EGF in high concentration (100
      ng/ml) by growth inhibition, being indifferent to lower (0.1-1 ng/ml)
      concentrations. At the same time, cells NIH 3T3, expressing human EGF receptor
      (HER14), and epithelial mammary cells HC11 increased 14C-thymidine incorporation
      into DNA after EGF addition. However, for HER14 cells stimulatory effect of EGF
      was twice weaker than that induced by serum, whereas the effect of EGF on 14C
      thymidine incorporation in DNA of cells HC11 was approximately 5 times stronger
      compared to serum. Therefore, cells HC11 may be referred to as EGF-dependent.
      Cell cycle analysis by fluorimetry showed that more than 90% of serum-starved
      HER14 and HC11 were in G0/G1. Within 19-20 h after stimulation by EGF 70-90% of
      HC11 cells and only 30-40% of HER14 cells were in S-phase. EGF removing from
      culture medium earlier than 9-11 h after stimulation blocked entering of HC11
      cells into S-phase, whereas such EGF-dependent period was not found for cells
      HER14. Thus, synchronization of progression through early stages of cell cycle,
      stimulated by EGF and the presence of well defined "early" (EGF-dependent) and
      "late" (EGF-independent) phases, make cells HC11 convenient object for studying
      physiological role of EGF receptor complexes endocytosis.

PMID- 10081092
TI  - [Vesico-urethral dysfunction].

PMID- 10081093
TI  - [Classification of vesico-urethral dysfunction].
AB  - Classification systems of bladder dysfunction are mainly based on functional and
      urodynamic characteristics. Under functional aspects classification relates to
      disturbances of storage and emptying function and the behaviour of its
      components, the bladder and the bladder outlet. The International Continence
      Society established a committee for the standardisation of terminology of lower
      urinary tract function and recommended worldwide accepted standards of
      terminology. These standards are the basis for any classification system and
      should be used to facilitate comparison of results. In addition, classification
      of bladder dysfunction should be completed by a clinical investigation to define
      the risks of underlying disorder.

PMID- 10081094
TI  - [Urological diagnosis in children with myelomeningocele].
AB  - Neurogenic bladder dysfunction in childhood is mostly caused by spinal
      dysraphism. The urologic diagnostic procedure tries to evaluate the underlying
      form of neurogenic bladder, dysfunction the associated disturbances at the upper
      tract and the development of changes by body growth. Therapeutic main aim is the
      conservation and protection of the kidney function and, secondly, the development
      of social dryness and a form of bladder emptying, that is related to the
      individual situation and associated disabilities. We report here about the
      diagnostic procedure and result of a group of 190 patients, that have been seen
      in our department since birth and for more than ten years continuously.
      Developmental changes of neurogenic bladder dysfunction has been found in more
      than 25% of the children. This figure shows the need of life-long close
      urodynamic follow-up.

PMID- 10081095
TI  - [Pathophysiology and diagnosis of functional disorders of micturition].
AB  - Voiding dysfunctions secondary to failure of adequate relaxation of the striated
      urinary sphincter or the smooth bladder neck should be considered in children
      with urinary day time incontinence and/or enuresis and recurrent urinary tract
      infections. The urodynamic findings resemble to those obtained in neuropathic
      bladders, but only a minority of the children suffer from neurologic disorders or
      anatomical obstruction. In the majority of cases a developmental delay of the
      central nervous system responsible for urinary control is assumed. Behavioural
      disturbances play another important etiological role. Therapy is based on
      behavioural modification.

PMID- 10081096
TI  - [Therapeutic possibilities in functional disorders of micturition].
AB  - Functional voiding disturbances can be due to failure of the detrusor or to
      discoordinated sphincter function during micturition. Therapeutical options are
      directed either to strengthening the contraction up to an adequate magnitude or
      to lowering the voiding resistance or can be aimed at influencing both. In a
      brief survey mechanical, pedagogical, electrotherapeutical, and surgical measures
      as well as drug treatment are critically examined. Conservative methods should
      always be attempted before surgical procedures are performed. Depending on the
      degree of severity and the etiology of the disease, a combined therapy can be
      useful. In the case of resistance to therapy, intermittent autocatheterism is to
      be preferred to permanent deviation via an indwelling catheter.

PMID- 10081097
TI  - [Conservative therapy of neurogenic disorders of micturition].
AB  - In neurogenic bladder dysfunction conservative treatment is preferred whenever
      possible and preservation of renal function remains the main topic. Additionally,
      a patient-related form of bladder management with decreased intravesical pressure
      and social dryness is needed. Therefore many strategies are available and after
      evaluation of the underlying neurogenic bladder dysfunction an individual kind of
      treatment can be used. Possible options are the clean intermittent catherization,
      anticholinergic drugs, detrusor triggering, electrical stimulation and bladder
      emptying by Valsalva's manouvre.

PMID- 10081098
TI  - [Detrusor myectomy (autoaugmentation) in the treatment of hyper-reflexive low
      compliance bladder].
AB  - After unsuccessful medical treatment of a neurogenic hyperreflexive bladder
      dysfunction further treatment options are the ileal bladder augmentation, the
      detrusor-myectomy (bladder auto-augmentation) and the sacral root
      deafferentation. All techniques lead to a low-pressure bladder with enlarged
      storage volume. The authors here report about their personal experience with the
      detrusor myectomy in 62 patients with hyperreflexive neurogenic bladder
      dysfunction from 1989 until 1998. Indication, surgical technique, and long-time
      results are presented.

PMID- 10081099
TI  - [Perioperative incidence of transfusions after allogenic kidney transplantation].
AB  - The requirement of blood transfusions was evaluated in a two compartment
      (retrospective/prospective) study in our renal transplantation program. Between
      July 1st, 1993 and December 31st, 1994 (observation period 1) we retrospectively
      investigated 110 patients with end stage renal disease and anemia undergoing
      kidney transplantation. Between January 1st, 1995 and December 31st, 1996
      (observation period II) the requirement of blood transfusions was followed
      prospectively in 134 patients after allogenic renal transplantation. The amount
      of blood drawn for preoperative diagnostic investigations was in observation
      period 1 significantly higher (280 ml) than in observation period II (150 ml) (p
      = 0.02). For postoperative diagnostic tests in observation period II
      significantly less blood (240 ml) was needed than in observation period 1 (510
      ml) (p = 0.01). The intraoperative blood loss was similar in both periods (170 ml
      vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for
      significantly increased amount of blood transfusions in patients with delayed
      graft function. The number of blood transfusions was significant lower in
      patients with primary graft function (p = 0.0001). There was no correlation
      between blood transfusions and the use of ATG/OKT3, surgical complications and
      reoperations. With an improved management of blood drawing for diagnostic tests
      after allogenic kidney transplantation the number of perioperative blood
      transfusions can be reduced significantly.

PMID- 10081100
TI  - [Langerhans-cell histiocytosis of the penis].
AB  - Involvement of the male genitalia by langerhans cell histiocytosis ist very rare.
      It has been reported in only three cases yet. We present a patient with recurrent
      disease of the skin of the penis and by proliferation involvement of the distal
      urethra and the corpus cavernosum. An overview of the disease and its therapy is
      given.

PMID- 10081101
TI  - [Lymph node staging of bladder neck carcinoma with positron emission tomography].
AB  - PET is a new method in nuclear medicine which examines the metabolism and not the
      morphology. Tumors show a higher rate of glycolysis than benign tissue and hence
      can be detected by radioactive glucose. This method has proved good for various
      tumors. In this study the lymph node staging of bladder cancer by PET was
      investigated. In 64 patients a PET of the pelvis after injection of
      fluorodeoxyglucose (FDG) was carried out preoperatively; the PET-results were
      compared with the histology of the OR specimen after classical pelvic
      lymphadenectomy. For lymph node staging positive nodes were found in 14 patients
      which was correct; a false-negative result was obtained in 7 patients. In 37
      patients the PET-result was true-negative and in 6 patients false-positive
      resulting in a sensitivity of 67%, a specificity of 86% and an accuracy of 80%.
      Therefore, our PET results are encouraging and seem to be better than those
      obtained by classical staging procedures such as CT or MRI.

PMID- 10081102
TI  - [Immunotesting--a conditio sine qua non for therapeutic BCG instillation in
      bladder neck carcinoma?].
AB  - The intravesical instillation of BCG (Bacillus Calmette-Guerin) in cases of
      relapsed superficial bladder cancer is an acknowledged kind of prophylaxis. It is
      uncertainly up to now whether a verification of the immune systems competence is
      necessary. The recommendations in this problem are very different. In conclusion
      to the recent literature we think that a verification of the immune system before
      BCG installation in the urinary bladder has not a prognostic value. Additionally,
      the legal obligingness of this immunotest is doubtful.

PMID- 10081103
TI  - [Secondary erectile dysfunction. Is oral medication in the diagnostic phase
      indicated?].
AB  - For patients with erectile dysfunction oral medication seems to be the most
      comfortable form of application. This can also be seen in the expectations
      looking forward to Sildenafil and other drugs in development. We present a
      prospective examination with the oral medication of 100 mg acecarbamol, 30 mg
      extract of cortex quebracho and 33 mg tocopherol acetate (Afrodor) in 100
      patients complaining secondary erectile dysfunction. The patients were treated
      unselected with 3 x 1 tablet/day during the diagnostic schedule. 14% of the
      patients were able to perform satisfying sexual intercourse after 4 weeks of
      medication and another 15% showed an increased libido. Therefore we suggest, that
      the application of an oral medication, might be useful, especially during the
      time of diagnostics. Especially for those patients who gain without invasive
      diagnostic tools as intracavernous injection.

PMID- 10081104
TI  - [An unusual case of genital tuberculosis. A case report].
AB  - We represent and discuss etiology, diagnosis as well as differential diagnoses of
      tuberculous orchtitis referring to an actual case of this rare disease. In the
      least of all cases one can conclude from the clinical symptoms on the tuberculous
      origin of the disease. Other differential diagnoses will set more frequently due
      to rarity of this disease. Quite a lot of cases a bacterial superinfection veils
      the sterile leucocyturia as main characteristic of genitourinary tuberculosis.
      Imaging diagnostics frequently fails to give indications of tuberculous origin of
      the lesion. As before the evidence of Mycobacteria tuberculosis is the most
      important parameter to proof a tuberculosis. Despite required microbiological
      cultivation to make a resistogram the polymerase chain reaction is a high
      sensitive and comparable fast method for detection of Mycobacteria even from
      tissue. In such dubious cases we recommend to perform an operative denudation due
      to frequently difficult delimitation from malignant testicular tumours.

PMID- 10081105
TI  - [Angiosarcoma of the kidney. Case report and review of the literature].
AB  - The primary renal angiosarcoma is a rarely seen highly malignant tumor. Making a
      diagnosis based on histology may prove difficult. Because of hematogenous
      formation of metastases and bad prognosis in most cases we recommend that the
      surgical intervention be followed by the well tolerated systemic chemotherapy
      with Doxorubicin and Ifosfamid.

PMID- 10081106
TI  - [Pain therapy in pediatric urology].

PMID- 10081107
TI  - [Guidelines for diagnosis of testicular tumors].

PMID- 10081108
TI  - [Too infrequently considered borderline specialties in urology].

PMID- 10081109
TI  - Animal pneumocystosis: a model for man.
AB  - Pneumocystis carinii is an important pulmonary pathogen responsible for morbidity
      and mortality in patients with AIDS. Apart from AIDS, cases of pneumocystosis
      have been reported in patients receiving immunosuppressive therapy associated
      with organ transplantation without chemoprophylaxis and in malignant blood
      diseases. In vitro models are only of limited interest because there is no
      continuous in vitro culture. The in vivo models have contributed a great deal to
      the understanding of human Pneumocystis carinii pneumonia. Indeed, animal models
      remain of prime interest for many purposes, principally comparative medicine,
      pathogenesis, epidemiology and immunology. Among animal models, the rabbit is a
      very susceptible host to P. carinii infection, and does not need glucocorticoid
      treatment. Moreover, antigenic and genomic data suggest that rabbit-derived
      Pneumocystis strains are more closely related to human Pneumocystis than those of
      mice or rats. We have therefore shown that the rabbit model permits the study of
      the pulmonary surfactant modification due to P. carinii infection. This model
      should be a very interesting model for pathogenesis or immune response studies in
      immunocompetent animals. The rabbit model could also be used for epidemiological
      studies. P. carinii transmission appears to be very rapid via contact of
      Pneumocystis-free rabbits with infected rabbits. These Pneumocystis-free animals
      could be helpful for characterizing the source and the reservoir and studying
      parasite transmission.

PMID- 10081110
TI  - Technical and economic evaluation method for use in improving infectious animal
      disease surveillance networks.
AB  - With hope of improving the increasing number of epidemiological surveillance
      networks for animal diseases set up in recent years, a qualitative and
      quantitative technical and economic evaluation tool was developed and then
      applied to three epidemiological surveillance networks: RENESA (a French
      surveillance network for salmonella and mycoplasma contamination in poultry
      production units subject to official sanitary controls), the French Foot and
      Mouth Disease Epidemiovigilance Network and REPIMAT (the epidemiological
      surveillance network in Chad for major cattle diseases). We identified critical
      points in epidemiological surveillance networks using a modified version of the
      hazard analysis: critical control point (HACCP) method. An evaluation grid was
      then developed and validated by experts who were consulted in accordance with the
      Delphi method. A questionnaire to collect the information required for the
      evaluation and a scoring guide were then designed. Our evaluation procedure also
      included a calculation of the annual operating costs for two of the three
      networks studied. On the basis of the detailed results of the technical and
      economic evaluation, we formulated specific suggestions for improving the
      networks. The cost of implementing these proposals was calculated. We then
      simulated the effects of implementing each of the proposed improvements and a new
      global evaluation score was determined for each network. The 'cost per point' of
      each improvement was then calculated and discussed. This tool for the technical
      and economic evaluation of epidemiological surveillance networks for animal
      diseases is proposed so that it may be tested on a far wider scale and eventually
      be used in improving the functioning of such networks and for risk analysis in
      international trade.

PMID- 10081111
TI  - Pharmacokinetics, bioavailability and dosage regimen of sulphadimidine in camels
      (Camelus dromedarius) under hot, arid environmental conditions.
AB  - A two-way crossover study was conducted in young Bikaneri camels (aged between 12
      and 18 months) during the hot summer season to determine the bioavailability,
      pharmacokinetics and dosage regimens of sulphadimidine (SDM). A dose of 100 mg.kg
      1 of SDM was used to study both the intravenous and oral pharmacokinetics of the
      drug. Analysis of the intravenous data according to a two-compartment
      pharmacokinetic model revealed that SDM was well distributed in the body
      (Vd(area):0.862 L.kg-1), had an overall body clearance of 0.035 +/- 0.019 L.h
      1.kg-1 and the elimination of half-lives was in the range of 14.2 to 20.6 h. The
      mean maximum plasma SDM concentration following oral administration was 63.23 +/-
      2.33 micrograms.mL-1, which was achieved 24 h after the oral administration. The
      mean bioavailability of SDM following oral administration was approximately 100%.
      To achieve and maintain the therapeutically satisfactory plasma sulphadimidine
      levels of > or = 50 micrograms.mL-1, the optimum dosage regimen for camels
      following either intravenous or oral administration would be 110 mg.kg-1 as the
      priming dose and 69 mg.kg-1 as the maintenance dose, to be repeated at 24 h
      intervals.

PMID- 10081112
TI  - [Detection of viral hemorrhagic septicemia virus (VHSV) in rainbow trout
      (Oncorhynchus mykiss) by reverse transcription followed by polymerase chain
      reaction. Diagnostic validation].
AB  - Viral haemorrhagic septicaemia virus (VHSV) is a fish pathogen that attacks
      rainbow trout (Oncorhynchus mykiss) farming. The only diagnostic method
      recognised by the European community for VHS is based on the detection of the
      viral agent in cell culture followed by an immunological identification of the
      pathogen. Reverse transcription followed by a double amplification of the
      polymerase chain reaction (RT-PCR) for the gene encoding the viral glycoprotein G
      is proposed here as an alternative method to the virus assay in cell culture. The
      RT-PCR was found to have three advantages over the viral assay method. First, the
      RT-PCR was found to be more rapid than the virus assay method (24 h compared to
      72-120 h). Second, this method was found to be more sensitive than the virus
      assay (2.10(-2) pfu of virus were detected per millilitre of viral suspension
      compared to 2.10(-1) pfu.mL-1 by inoculation of the cell lines EPC and RTG2).
      Third, the RT-PCR was shown to be specific towards the VHS virus assay
      (represented by its four serotypes VHS I, VHS II, VHS 23/75 and VHS IV). Moreover
      no amplification was obtained with the other rhabdoviruses used: infectious
      haematopoietic necrosis virus (American strain Amend 72, WRAC, RB, SRVC) and
      French reference strain 69/87, eel viruses, spring viraemia of carp virus and
      pike fry virus. The validation of this method was performed on organs removed
      from experimentally infected rainbow trout and ovarian fluid samples from farmed
      broodfish from D0 to D150. By using RT-PCR between D30 and D60, 13 samples from
      nine experimentally infected trout (ten kidney-spleen pools and three brains)
      tested positive, whereas only nine samples (four kidney-spleen pools and five
      brains) from six fish were positive at D30. The last positive response was
      obtained by RT-PCR at D60 for kidney-spleen pools from three fish. At D150, all
      the results were negative. From the 60 ovarian fluid samples tested, 28 were VHS
      positive by the RT-PCR versus 15 by the virus assay method. Eleven out of the 60
      broodfish had neutralised anti-VHS, six were negative by RT-PCR and by the virus
      assay, four were positive by RT-PCR and negative by virus assay and one positive
      by both methods. The specificity, sensitivity and rapidity of the RT-PCR method
      makes it an attractive alternative to classical virological methods currently
      recommended by European Fish Health Surveillance Programmes.

PMID- 10081113
TI  - Pattern of diarrhoea in newborn beef calves in south-west France.
AB  - A prospective study was carried out on 94 randomly selected beef herds in the
      Midi-Pyrenees region in France. The objective was to describe diarrhoea and
      mortality in beef calves from birth to 30 days of age. Calves (3,080) were
      followed from December 1995 to April 1996, and a total of 700 visits allowed
      records of herd management practices, individual data and environmental
      conditions to be collected. The incidence rate for diarrhoea during the neonatal
      period was 14.6%, and varied markedly between herds. Eighteen herds did not
      suffer from diarrhoea, while five herds had an incidence of more than 50%.
      Results indicate that 52% of diarrhoea appears during the first week and only 15%
      after the second week of life. The greatest risk of diarrhoea for a calf was
      during the first and second weeks of life (7.9 and 6.5 times, respectively). The
      month of birth was also significantly associated with morbidity, the highest
      incidence was observed in December and March (17.6 and 23.6%, respectively).
      Escherichia coli was isolated from 20.3% of faecal samples and appeared earlier
      during the first days of life. Rotavirus was frequently isolated (47.4%) from
      samples. Coronavirus was positive for only 16.5% but was significantly associated
      with diarrhoea. Cryptosporidium was less frequent (15.6%). The global mortality
      rate was 3.6% and was two-times higher in December than in other months. Forty
      per cent of herds did not exhibit mortality, and 10% had mortality rates greater
      than 10%. This study confirms previously reported data, and with greater
      precision and details on diarrhoea and mortality incidences among herds, age and
      month of birth in suckling beef calves.

PMID- 10081114
TI  - Effects of experimentally induced Theileria annulata infection on the
      pharmacokinetics of oxytetracycline in cross-bred calves.
AB  - The effects of an experimental Theileria annulata infection on the intravenous
      (10 mg kg-1) pharmacokinetics of oxytetracycline (OTC) were investigated in
      crossbred calves. The serum concentration-time curve of oxytetracycline before
      and after the experimental infection was best described by an open two
      compartment model. The experimental infection was induced by a subcutaneous
      administration of ground-up tick supernate (GUTS) equivalent to 30 Hyalomma
      anatolicum anatolicum ticks infected with Theileria annulata. It produced a
      definite temperature rise and symptoms of clinical disease in the calves. The
      haemoglobin, packed cell volume (PCV), white blood cell (WBC) counts and serum
      Cu, Fe and Zn concentrations decreased after onset of the infection. The
      distribution and elimination half-lives (t1/2 alpha and t1/2 beta), volume of the
      central compartment (Vc), AUC0-infinity, AUMC and mean residence time (MRT), were
      significantly reduced (P < or = 0.05) and the hybrid rate constants K12, Kel,
      K12/K21 ratio and total body clearance (ClB) of oxytetracycline were
      significantly (P < or = 0.05) increased after infection. The infection, however,
      had no effect on the C0, K21, apparent and steady-state volumes of distribution
      (Vd(area) and Vdss) of the drug. The above changes may necessitate changes in the
      dosage regimen of oxytetracycline used to treat Theileria infections in cattle
      under field conditions.

PMID- 10081115
TI  - A field study on estrus detection in lactating beef cattle.
AB  - Estrus detection efficacy and heat detection protocol were studied by means of a
      field study carried out on 878 lactating beef cows in 60 French herds. Average
      herd size was 48, and 75% of the farmers partly or exclusively used artificial
      insemination. The cows were calved between October 1992 and March 1993. Estrus
      was recorded daily by the farmers. Cycling status was determined by progesterone
      radioimmuno-assay 2 months after calving. The relationship between the estrus
      detection protocol and the delay period from calving to first observed estrus was
      analysed using survival curves and the Cox proportional hazard model, adjusting
      for confounders. Seventy-one percent of the cows were seen in estrus by the
      farmers; the interval between calving and the first observed estrus ranged from 9
      days to more than 5 months and the median was 56 days. Two months after calving,
      44% of the cycling cows had not been seen in heat by the farmers and 11% of the
      non-cycling cows had been reported to have been in estrus. The heat detection
      protocol varied widely between farmers, depending on the considered estrus signs,
      schedule and time spent looking for signs. Two factors were significantly related
      to a shorter interval from calving to first observed heat: the use of artificial
      insemination (which relates to the farmer's interest in heat detection) and an
      overall daily time spent for heat detection greater than 1 h. Cows in tie stalls
      had a delayed interval to the first observed estrus. These results show that many
      farmers did not adapt their reproduction practice sufficiently to an earlier
      calving period. There is room for improvement since in many cases the heat
      detection protocol does not match the required standards for optimal heat
      detection.

PMID- 10081116
TI  - Quantitation of histochemical staining of salivary gland mucin using image
      analysis in cats and dogs.
AB  - Two different, computer-based, image analysis methods were employed to complement
      subjective assessment of patterns of mucin staining (by periodic acid
      Schiff/alcian blue, aldehyde fuchsin/alcian blue and potassium hydroxide-alcian
      blue/phenylhydrazine hydrocholoride) in digitised images of sections of major and
      minor salivary glands from cats and dogs. Image analysis based on red, green and
      blue (RGB) staining was not suitable for quantitation of histochemical staining
      of mucin in salivary glands. Image analysis based on hue, saturation and
      lightness (HSL) allowed quantitative assessment of staining by different stain
      components and of mixed staining, and enabled comparison of staining of different
      glands in dogs and cats. Quantitative analysis based on HSL allowed
      differentiation of differences in staining patterns of major and minor cat and
      dog salivary glands, and between the species; such differences would have been
      impossible to distinguish on subjective grounds alone. Quantitative assessment of
      normal salivary gland histochemistry allows comparison with staining patterns in
      disease.

PMID- 10081117
TI  - Incidence of Oestrus ovis infestation in Borno-white Sahel goats in the semi-arid
      zone of Nigeria.
AB  - Research conducted on the incidence of Oestrus ovis in Maiduguri showed that
      53.8% of the 4,000 Borno-White Sahel goats examined were parasitised. The mean
      year-round infestation per goat was 2.03 larvae. Adult goats had a higher
      infestation rate than younger ones (60 versus 47.5%). Infestation rates for the
      females and males were 55.2 and 52.2%, respectively. Nevertheless there was no
      statistical significance between values for the different age and sex groups
      studied. Different larval stages were encountered throughout the year with a 3rd
      instar peak between May and September and a first instar peak from June to
      October suggesting a fly period between June and October.

PMID- 10081118
TI  - Infection of Lymnaea truncatula and Lymnaea glabra by Fasciola hepatica and
      Paramphistomum daubneyi in farms of central France.
AB  - Natural infection of Lymnaea glabra and Lymnaea truncatula by Fasciola hepatica
      and/or Paramphistomum daubneyi was studied at two periods of risk (June-July and
      September-October) in 11 French farms known for their high prevalences of F.
      hepatica infection in ruminants. A total of 1,778 L. truncatula and 2,396 L.
      glabra measuring 6 mm or more in height were collected to determine the
      prevalence of natural infection with F. hepatica and P. daubneyi. The role of
      four factors, i.e. season, snail co-infection (F. hepatica-P. daubneyi), ruminant
      host and the existence of single or mixed intermediate host communities, was
      investigated. There were no differences in prevalences between the two risk
      periods. Co-infections in L. glabra were more frequent than expected. The
      prevalences of infection with F. hepatica or P. daubneyi in L. glabra were higher
      in farms rearing sheep than in farms rearing cattle. A similar finding was also
      noted for L. truncatula infected with P. daubneyi only. L. glabra was a much
      better intermediate host for F. hepatica and P. daubneyi when it was the only
      available snail, possibly indicating an adaptation of parasites to their less
      usual host in local conditions. The two trematodes preferably developed in L.
      truncatula rather than in L. glabra when both host species lived in the same
      places.

PMID- 10081119
TI  - Conclusions of the European Union Conference on 'The microbial threat', 9-10
      September 1998. The Copenhagen Recommendation. Ministry of Health Ministry of
      Food, Agriculture and Fisheries.

PMID- 10081120
TI  - Reduction of cardiovascular mortality in type-2 diabetes by aggressive and early
      intervention strategies.

PMID- 10081121
TI  - Genetics and metabolism of lipoprotein(a) and clinical implications (Part 2).

PMID- 10081122
TI  - Mycobacteria other than tuberculosis with an emphasis on Mycobacterium xenopi in
      clinical specimens from AIDS patients at the University Hospital of Vienna from
      1989 to 1996.
AB  - This study was carried out to provide an overview of the frequency of various
      mycobacterial species isolated from AIDS patients at the University Hospital of
      Vienna from 1989 to 1996. Mycobacterium xenopi was found to be the second most
      common nontuberculous mycobacterial species (92 specimens from 30 patients) and
      was cultured predominantly from respiratory tract specimens. In 55% of patients,
      chest X-rays taken at the time of isolation demonstrated pathologic changes which
      could not be attributed to another cause. Therefore, according to our results,
      Mycobacterium xenopi should be viewed as an infectious agent rather than a
      contaminant in AIDS patients.

PMID- 10081123
TI  - [Long-term treatment with botulinum toxin: dosage, treatment schedules and
      costs].
AB  - Local injection of botulinum toxin A (BTX) is considered as the treatment of
      choice for spasmodic torticollis (ST), blepharospasm (BS) and, with certain
      limitations, for hemifacial spasm (HFS). Long-term data from 89 patients with ST,
      39 patients with BS and 15 patients with HFS were evaluated and subgroups of
      patients who received at least three (60 ST, 17 BS, 9 HFS), six (35 ST, 10 BS, 8
      HFS) and nine (26 ST) re-injections were formed. These groups were investigated
      in regard of increases in the dosage of BTX and in regard of shorter treatment
      intervals in cases of repeated treatment. Annual drug costs were calculated from
      these data. Patients treated at least three times were asked to fill out a
      questionnaire concerning satisfaction and the quality of life after BTX
      treatment. Furthermore, the patients' "willingness to pay" for BTX treatment was
      investigated. Our calculations showed neither a significant increase in the
      dosage of BTX nor a significant reduction in the length of treatment intervals
      after 3 or 6 treatment sessions. Annual drug costs for BTX for the treatment of
      ST were 10,542 ATS, of BS 2847 ATS and of HFS 1029 ATS. 86.1% of patients with
      ST, 88.9% with BS and 100% with HFS were very satisfied or satisfied with the BTX
      treatment. In all 3 diagnostic groups, a significant mean improvement of quality
      of life was measured on a visual analogue scale (p < 0.001). We conclude that the
      injection of botulinum toxin A is a highly effective and cost effective treatment
      for ST, BS and HFS, and significantly increases the quality of life of all these
      patients.

PMID- 10081124
TI  - Cardiovascular risk factors as predictors of mortality in type II diabetic
      patients.
AB  - BACKGROUND: Mortality among diabetic patients is high and attempts have been made
      to find clinical markers which would help to identify patients at risk. MAIN
      PURPOSE: The purpose of this study was to assess whether cardiovascular risk
      factors like previous myocardial infarction, left ventricular dysfunction,
      hypertension, renal insufficiency, and 24-hour mean or minimum heart rate,
      significantly contribute to the mortality in this group of patients. METHODS: 45
      male patients with type II diabetes mellitus were studied by ambulatory
      electrocardiography to obtain the information about the 24-hour mean and minimum
      heart rates; records from baseline hospitalization were reviewed for clinical
      variables. After 55 months mortality data were retrieved. Cox's proportional
      hazards regression model was used to study the effect of clinical variables on
      mortality in multivariate analysis. RESULTS: All-cause mortality was 38%. The
      groups of survivors and nonsurvivors differed significantly in terms of age, the
      presence of left ventricular dysfunction and renal insufficiency. No significant
      difference in 24-hour mean or minimum heart rate was registered. In the Cox's
      model, the presence of left ventricular dysfunction, renal insufficiency and age
      significantly and independently predicted mortality. CONCLUSION: The present
      study, showed that left ventricular dysfunction and renal insufficiency were
      related to the all-cause mortality of type II diabetic patients independently of
      age, after 55 months of follow-up. Prognostic significance of 24-hour mean or
      minimum heart rate has not been proven.

PMID- 10081125
TI  - Acetabular fractures: operative management and long term results.
AB  - INTRODUCTION: While the undisplaced acetabular fractures have a good prognosis
      after conservative treatment, the management of the displaced fractures has been
      a controversial issue over the last decades with variable results in their
      treatment and prognosis. Anatomical reduction can be only achieved operatively.
      The long term outcome of 209 patients with displaced acetabular fractures treated
      by open reduction and internal fixation was presented. MATERIAL AND METHODS:
      Between 1972 and 1996, 209 patients with a mean age of 38 years (15-62a) were
      treated for displaced acetabular fractures operatively. 161 patients could be
      followed up over a period of 2 to 20 years. The function of the hip joint in
      correlation with radiological results was evaluated according to the scheme of
      Merle d'Aubinge. RESULTS: Patients with single column fractures showed 90% good
      or excellent results followed by 55% good or excellent results in patients with
      transverse fractures. The highest rates of complication (20% osteoarthritis, 6%
      femoral head necrosis, 9% heterotopic ossification) were observed in both column
      fractures and in transverse and posterior wall fractures. Deep infection was
      observed in 6 cases (4%), superficial wound infection in 8 cases (5%). Primary
      sciatic nerve palsy was seen in 10 cases (6%) and postoperative peroneal nerve
      palsy in 6 cases (4%), all of which improved during the rehabilitation period.
      CONCLUSION: Displaced acetabular fractures of the weight bearing part of the
      dome, i.e. transtectal fractures, should be treated operatively. The operation
      should preferably be performed within one week after the injury.

PMID- 10081126
TI  - Cholestasis and liver cell damage due to hypersensitivity to erythromycin
      stearate--recurrence following therapy with erythromycin succinate.
AB  - Erythromycin is a frequently used antibiotic in patients with atypical
      respiratory infection and/or an allergy to penicillin. We report the case of a
      young woman who developed severe cholestasis and jaundice following treatment
      with erythromycin stearate. Two years later her general practitioner prescribed
      erythromycin succinate for pharyngitis. She experienced a severe second episode
      of jaundice and malaise. Different esters of erythromycin have been introduced to
      reduce side effects such as allergic reactions to erythromycin. The findings in
      our patient underline the fact that hypersensitivity is caused by the
      erythromycin molecule, independent from the type of esterification. Because of
      these side effects newer makrolides should be given preference over erythromycin.

PMID- 10081127
TI  - [Clinical typology of contrast content obsessions in borderline mental diseases].
AB  - 40 patients were observed (16 men, 24 women, mean age 27 years) with the
      obsessions of the contrast contents (14-homocidophobia, 18-suicidophobia, 8
      combined homo- and suicidophobia). Two types of contrast obsession (CO) were
      recognized: contrast phobias with anxiety about possibility to commit
      autodestructive or criminal actions and contrast obsessions with anxious doubts
      about committing either violence or murder. CO of first type were determined by
      the fear of lack of self-control and possibility to commit autodestructive or
      criminal actions. Such obsessions are accompanied by bright images, massive
      somato-vegetative symptomatology and rapid formation of avoidance behaviour. CO
      of second type are characterized by pathologic doubts about committing violence
      or murder and accompanied by strong desire to check again and obsessive self
      analysis. CO of first type belong to the spectrum of anxious-phobic disorders and
      are phobic in their nature; within acute phobic fit, similar in manifestations to
      a panic attack; they are associated with other phobic disorders and manifest like
      phobic depressions. On the contrary, CO of second type are true obsessive
      phenomena, and isolated, combine with obsessions of the repeated control, and
      with different types of depressions only in half of the cases.

PMID- 10081128
TI  - [Characteristics of mental disorders in patients with rheumatoid arthritis].
AB  - Peculiarities of mental disorders in patients with rheumatic arthritis were
      studied in 70 patients aged 20-60 years. The most typical mental disorders were:
      asthenic symptomatology, depressive phenomena with anxiety, fears, ideas of self
      accusation, a peculiar variation of the syndrome of dysmorphophobia due to
      defects of appearance, stable disorders of sleep, psychopathic-like disorders
      and, quite frequently, manifestations of psycho-organic syndrome.

PMID- 10081129
TI  - [Neuroprotective effects of glycine in the acute period of ischemic stroke].
AB  - Both the efficiency of glycine in the acute period of hemispheric ischemic stroke
      and mechanisms of its action were studied in a double blind placebo-controlled
      trial including 200 patients. Orgogozo's and Scandinavian scales for objective
      assessment of the condition severity and of a degree of neurologic deficiency,
      and Bartel's scale--for evaluation of functional recovery were used and
      measurements were made of the levels of autoantibodies to the structural
      component of glutamate NMDA-receptors in blood serum and concentrations of
      neurotransmitter amino acids and of the products of lipid peroxidation in
      cerebrospinal fluid. Sublingual glycine application in daily dose of 1-2 g was
      found effective beginning with the first 6 hours of the stroke development during
      5 days. Multicomponent neuroprotective action of glycine was established directed
      at correction of the unbalance between stimulating and inhibiting aminoacidergic
      neurotransmitters, as well as at a decrease of excitotoxicity and oxidant stress.

PMID- 10081130
TI  - [Treatment of acute attacks of migraine by dihydergot: nasal aerosols].

PMID- 10081131
TI  - [Use of tianeptine (coaxil) in the treatment of late-life depression].
AB  - Efficacy and safety of tianeptine (coaxil) for treatment of depressions in old
      age were studied in 15 depressed patients at the age of 54-78 years meeting ICD
      10 criteria for depressive episode. Open method with a set of rating scales was
      employed. After the 28-day treatment relief of depressive symptoms was registered
      by all the scales since the therapy day 7. The degree of improvement on HAMD
      scale was 50%, amount of responders--60%. The improvement of cognitive functions
      by the end of therapy was noted. Clinical predictors of Coaxil efficacy were
      determined by means of correlation and factor analyses. Relationship between the
      therapy efficacy and severity of some symptoms in the structure of depression
      were analyzed. The greatest efficacy of Coaxil was found in depression with
      prevalence of asthenic and somatovegetative symptoms, in patients with mild
      anxiety opposite the decrease of the effect in those with severe agitated
      depressions. The analysis of both frequency and severity of the side-effects has
      shown good tolerance to Coaxil. The adverse effects manifested with mild
      gastrointestinal disturbances and drowsiness during daytime.

PMID- 10081132
TI  - [Principal indications and contraindications of the use of extracorporeal
      hemocorrection in psychiatry].
AB  - Analysis of different aspects of application of extracorporeal hemocorrection
      (EH) in psychiatric practice allows to make a conclusion about the necessity of a
      differential approach to the use of isolated and combined procedures. The latter
      were assessed by the results of combined treatment of 226 patients. Indications
      and contra-indications for EH use in psychiatric practice are outlined.

PMID- 10081133
TI  - [Levels of neurotransmitter amino acids in the cerebrospinal fluid of patients
      with acute ischemic stroke].
AB  - The dynamics of the levels of both excitatory (aspartate, glutamate) and
      inhibitory (GABA, glycine) neurotransmitter amino acids was estimated in
      cerebrospinal fluid of 110 patients with hemispheric ischemic stroke. A
      significant increase of the contents of glutamate and aspartate was found
      beginning with the first 6 hours of the disease onset. The degree and duration of
      such elevation correlated with severity of the stroke. Maximal GABA and glycine
      levels were registered to the end of the 1st day of the stroke, that reflected
      delayed triggering of the protective inhibitory mechanisms. It was established
      that insufficiency of GABA-mediation in hemispherical location of the stroke was
      much responsible for both the severity of its clinical manifestations and
      potential of the restorative processes. Early significant biochemical criteria
      for objective assessment of the severity of cerebral ischemia as well as of the
      stroke course and outcome were defined. The most unfavourable prognostic signs
      were low GABA concentration (or impossibility of its evaluation) during the first
      days of the stroke, progredient elevation of the aspartate level until the 3d day
      of the disease and the severe fall of glutamate concentration (in spite of its
      initial increase on the 1st day).

PMID- 10081134
TI  - [Sex role identity in persons with paraphilias].
AB  - Specificity of sexual role identity was studied in individuals with disorders of
      sexual drive with focus on the study of individual expression of sexual role
      signs and correlation between value-regulatory and standard-role components of
      sex self-consciousness in paraphilias. By means of modified psychologic
      projective methods, two groups who had committed criminal sex delicts were
      examined: a group with different variations of paraphilias (69 examinees), a
      group without any anomalies of sexual drives (57 examinees), a control group (65
      healthy men). The data obtained about a divergence of value-regulatory and
      standard-role components of sexual role self-consciousness indicated disorder of
      the stage of forming of stable role self-identity at juvenile age and reflected
      difficulties in interiorization of male sex-role standards in individuals with
      the disorders of sex drive.

PMID- 10081135
TI  - [Clinical aspects and effectiveness of the treatment of patients at a
      gerontologic-psychiatric day hospital].
AB  - 233 patients, older than 60 years old, from daily gerontologic out-patients
      hospital (DGH) were observed during 5 years. They had almost all forms of mental
      pathology inherent to the elderly. Treatment under DGH conditions was effective
      in patients with borderline conditions as well as in those with endogenic
      psychoses without psychotic states. Besides, a therapeutic effect was found in
      individuals with either organic or vascular cerebral diseases manifesting with
      pseudoneurotic syndrome, as well as in patients with residual symptomatology
      resultant from previous organic damage of the brain of traumatic or infectious
      origin. For patients with atrophic cerebral diseases (senile dementia,
      Alzheimer's disease) treatment was useless.

PMID- 10081136
TI  - [Effects of the results of randomized trials on the tactics of management of
      patients with acute stroke].

PMID- 10081137
TI  - [Pseudohysteria in patients with melancholia].

PMID- 10081138
TI  - [Estimation of cerebrovascular reserve in atherosclerotic lesions of the carotid
      arteries].

PMID- 10081139
TI  - [Mechanisms of brain tissue damage in acute focal cerebral ischemia].

PMID- 10081141
TI  - In vivo energy dispersive X-ray fluorescence for measuring the content of
      essential and toxic trace elements in teeth.
AB  - The calibration and application of a facility, based on energy dispersive X-ray
      fluorescent analysis (EDXRF) using 109Cd as an excitation source, for in vivo and
      in vitro estimation of Ca, Pb, Sr and Zn in tooth enamel is described. During the
      in vivo measurements, the device ensures tissue protection of face and mouth
      cavity from radiation, and only a small part of tooth surface under study is
      irradiated. To calibrate the facility, the contents of Ca, Sr and Zn were
      analyzed simultaneously in the enamel of 50 teeth by EDXRF and instrumental
      neutron activation analysis (INAA). Standards prepared from powdered tooth enamel
      with additions of chemically pure lead compounds were used to calibrate for lead
      graduation. Enamel calcium is suggested as an internal standard during in vivo
      EDXRF of teeth. The content of enamel Sr, Zn and Pb was determined by EDXRF in 35
      permanent intact teeth of teenagers and adults. It was shown that lead
      concentration didn't exceed 3 micrograms/g for all the teeth.

PMID- 10081142
TI  - A review of low-level tritium systems and sensitivity requirements.
AB  - Data from three international intercomparison projects are used to study the
      state of the tritium low-level technique and to set a realistic sensitivity level
      that should be demanded in ultralow-level tritium work, mainly in hydrology and
      oceanography. Only two laboratories reach the required goal, a standard deviation
      < or = 0.03 TU for weak samples. The methods used are described and important
      parameters illustrated graphically. Possible improvements in the measuring
      techniques are discussed, including the design of better counting systems.

PMID- 10081143
TI  - Prediction of the relative activity levels of the actinides in a fallout from a
      nuclear reactor accident.
AB  - The relative activities of the actinides that can be expected in a fresh fallout
      from a nuclear reactor (BWR, PWR, RBMK) accident have been estimated from fuel
      composition calculations. The results can be used to (1) adapt analytical methods
      to better suit emergency situations, (2) estimate the activity levels of
      radionuclides not measured and (3) estimate the relative activities of nuclides
      in unresolved alpha-peaks. The latter two can be applied to investigations
      concerning the Chernobyl fallout, in addition to emergency situations.

PMID- 10081144
TI  - Determining soil contamination profiles from intensities of capture-gamma rays
      using above-surface neutron sources.
AB  - Four methods are presented to estimate contaminant concentration profiles in soil
      from the intensities of neutron-induced capture-gamma photon intensities measured
      at the soil surface. In particular, the method of linear regularization with and
      without an iterative positivity constraint, the Backus-Gilbert method, and the
      maximum entropy method are applied to the soil contamination problem. Example
      results obtained with the four methods are given for photon intensities
      calculated for idealized test contaminant profiles in soil irradiated by neutron
      sources above the surface.

PMID- 10081145
TI  - Distribution pattern of 90Sr and 137Cs in the Nile delta and the adjacent regions
      after Chernobyl accident.
AB  - Strontium and cesium contents in surface soil samples across the Nile Delta and
      the north coast of Egypt after the Chernobyl accident have been investigated. The
      concentration of 137Cs and 90Sr was determined using a high resolution gamma
      spectrometer based on hyperpure germanium detector (HPGe) and a liquid
      scintillation counter (LSC) respectively. 90Sr was determined through its decay
      product 90Y using Cerenkov counting. The determination of 90Sr was based on
      tributylphosphate (TBP) extraction of yttrium from nitric acid extract of ashed
      samples. The radioactivity of soils ranged between 18.5 and 2175 Bq/m2 with a
      mean of 652 Bq/m2 and 234 and 3129 Bq/m2 with a mean of 760 Bq/m2 for 137Cs and
      90Sr respectively. An estimated absorbed dose equivalent due to the measured
      deposit of 137Cs was found to be 0.062 murem/h.

PMID- 10081146
TI  - Effects of PEG-lipids on permeability of phosphatidylcholine/cholesterol
      liposomes in buffer and in human serum.
AB  - The permeability of liposomal membranes was studied as a function of the amount
      of incorporated PEG-lipid. The fluorescent dyes ethidium, propidium and 5(6)
      carboxy fluorescein were used as markers for measurements of spontaneous leakage.
      The results show that addition of up to 8 mol% of PEG(2000)-DSPE into liposomal
      membranes of DSPC/Cho and EPC/Cho reduces the permeability of carboxyfluorescein
      in buffer solution. In contrast, the leakage of the more amphiphilic dye ethidium
      was not to any measurable extent affected by PEG-lipid inclusion. Another
      important difference was that ethidum leakage showed a clear dependence on
      temperature whereas leakage of carboxyfluorescein from pegylated liposomes did
      not. We conclude that the mechanisms by which the two dyes permeate the liposomal
      bilayer are qualitatively different. Both ethidium and carboxyfluorescein did
      interact with human serum components in a way that made measurements in serum
      unreliable. The more hydrophilic ethidium analogue propidium was shown not to
      interact with human serum components to any detectable extent. This made
      propidium suitable for permeability determinations in human serum. It was found
      that liposomes composed of pure EPC or EPC with 5 mol% DSPE-PEG, displayed a
      dramatic increase in permeability when subjected to a medium composed of 20%
      human serum in buffer. Addition of 40 mol% cholesterol to the EPC bilayers
      reduced the observed release rate in human serum substantially, whereas no
      stabilizing effect was observed upon PEG-lipid inclusion.

PMID- 10081147
TI  - Liquid chromatography with particle-beam electron-impact mass spectrometry of
      diacylglycerol nicotinates.
AB  - Several synthetic diacylglycerols and natural mixtures derived from soybean, egg
      yolk, and bovine liver phosphatidylcholines were examined in the form of
      nicotinate derivatives by liquid chromatography with particle-beam electron
      impact mass spectrometry. High-performance liquid chromatography was carried out
      in the reversed-phase mode with a base-deactivated octyl-/octadecylsilyl
      stationary phase. The nature (size and degree of unsaturation) of the acyl
      residues was readily determined from the mass spectra. Uniquely, the positions of
      the double bonds could be deduced, although this became increasingly difficult as
      the degree of unsaturation of diacylglycerols containing mixed acyl residues
      increased. Reverse 1,2-diacylglycerol isomers could be distinguished by their
      mass spectra.

PMID- 10081148
TI  - Long-chain N-acylethanolamines inhibit lipid peroxidation in rat liver
      mitochondria under acute hypoxic hypoxia.
AB  - Two long-chain N-acylethanolamines (NAEs), N-palmitoyl- (NPE) and N
      stearoylethanolamine (NSE), are shown to inhibit an in vitro non-enzymatic Fe(2+)
      induced free radical oxidation of lipids in the liver mitochondria of rats with
      hypoxic hypoxia. NSE appeared to be more effective than NPE in suppressing some
      kinetic parameters of the Fe(2+)-induced chemiluminescence. The inhibitory action
      of NAEs on non-enzymatic lipid peroxidation supports the idea that they possess
      membrane protective properties.

PMID- 10081149
TI  - Conformational basis of the phospholipid requirement for the activity of SR
      Ca(2+)-ATPase.
AB  - The delipidated sarcoplasmic reticulum (SR) Ca(2+)-ATPase was reconstituted into
      proteoliposomes containing different phospholipids. The result demonstrated the
      necessity of phosphatidylcholine (PC) for optimal ATPase activity and
      phosphatidylethanolamine (PE) for the optimal calcium transport activity.
      Fluorescence intensity of Fluorescein 5-isothiocyanate (FITC)-labeled enzyme at
      Lys515 as well as the measurement of the distance between 5-((2-[(iodoacetyl)
      amino] ethyl) amino)naphthalene-1-sulphonic acid (IAEDANS) label sites
      (Cys674/670) and Pr3+ demonstrated a conformational change of cytoplasmic domain,
      consequently, leading to the variation of the enzyme function with the
      proteoliposomes composition. Both the intrinsic fluorescence of Trp and its
      dynamic quenching by HB decreased with increasing PE content, revealing the
      conformational change of transmembrane domain. Time-resolved fluorescence study
      characterized three classes of Trp residues, which showed distinctive variation
      with the change in phospholipid composition. The phospholipid headgroup size
      caused the conformational change of SR Ca(2+)-ATPase, subsequent the ATPase
      activity and Ca2+ uptake.

PMID- 10081150
TI  - Antioxidant activity of quercetin and myricetin in liposomes.
AB  - The antioxidant activity during storage at 30 degrees C of quercetin, myricetin
      and alpha-tocopherol in small unilamellar liposomes has been investigated.
      Myricetin was more effective than alpha-tocopherol as an antioxidant in liposomes
      under all conditions studied. At pH 5.4 with a concentration of 10(-2) mol/mol
      phospholipid, myricetin has been shown to be the strongest antioxidant followed
      by quercetin and alpha-tocopherol. Cupric chloride and ferric chloride strongly
      reduced the antioxidant activity of myricetin and quercetin with cupric chloride
      causing a stronger reduction in activity than ferric chloride. At a pH of 7.4,
      quercetin was less effective than alpha-tocopherol at a concentration of 10(-2)
      mol/mol phospholipid, but it's activity increased more strongly with
      concentration and it was very effective at a concentration of 5 x 10(-2) mol/mol
      phospholipid.

PMID- 10081151
TI  - Morphologic study of the testes from spontaneous unilateral and bilateral
      abdominal cryptorchid boars.
AB  - Macroscopical and histological characteristics were examined in both testes from
      three healthy boars, three boars with unilateral abdominal cryptorchidism on the
      right side, and three boars with bilateral abdominal cryptorchidism. Abdominal
      cryptorchidism, unilateral and bilateral, provoked a significant decrease of the
      weight and volume of the ectopic testes. The scrotal testis of the unilateral
      cryptorchid boars showed an increase in its volume and weight. Cryptorchidism
      also induced abnormalities in the histological structure of seminiferous tubules,
      lamina propria, and interstitial tissue of the abdominal testes. The number of
      seminiferous tubules decreased; the seminiferous epithelium was constituted by
      few spermatogonia with an atypical pattern and by abnormal Sertoli cells. The
      lamina propria showed a variable degree of thickening and collagenization. The
      interstitial tissue was very developed but displayed a decrease in the Leydig
      cell population. These abnormalities were more critical in bilateral
      cryptorchidism than in unilateral cryptorchidism. The scrotal testis of the
      unilateral cryptorchid boars showed normal appearance, but a decrease of the
      number of seminiferous tubules was observed. Moreover, the seminiferous tubules
      showed impaired spermatid maturation. The alterations observed in the abdominal
      testes of the unilateral and bilateral cryptorchid boars were attributed to
      defective proliferation and differentiation of Sertoli cells and Leydig cells.
      The anomalies in the scrotal testis of the unilateral cryptorchid boars were due
      to disturbances in the Sertoli cell activity.

PMID- 10081152
TI  - Morphology of rhinoceros platelets.
AB  - Basic hematological information about rhinoceros species is limited. In this
      study, we have determined the platelet counts and described the platelet
      morphology of free-living white (Ceratotherium simum) and black (Diceros
      bicornis) rhinoceros using light and electron microscopy. The platelet counts of
      the two species were similar, but there were significant differences in platelet
      size as well as morphology between the species. The presence of large, nondiscoid
      platelet forms, resembling proplatelet or stress platelet forms, were observed in
      both, although not as often in the white rhinoceros as in the black rhinoceros.

PMID- 10081153
TI  - Morphometry, histochemistry, and innervation of cervical shoulder muscles in the
      cat.
AB  - Morphometric and histochemical methods were used to estimate the force-developing
      capabilities and fiber-type contents of four muscle complexes (rhomboideus,
      levator scapulae, trapezius, and sternomastoideus) that link the shoulder girdle
      to the skull and cervical vertebrae. Each complex contained at least two member
      muscles that were distinctive architecturally and often had specialized
      innervation patterns. Trapezius and sternocleidomastoideus were innervated by
      both cranial nerve XI and cervical spinal nerves. Glycogen depletion of trapezius
      suggested that the nerves derived from cervical roots might be entirely sensory.
      Muscles within each complex varied in physiological cross-sectional area from
      less than 0.1 cm2 to greater than 1 cm2. They showed differences in fiber-type
      composition that suggested specialized roles for different behaviors. The
      morphometric features of the cervical shoulder muscles suggest that they have
      considerable potential to produce head movements and should be incorporated into
      feline head-movement models.

PMID- 10081155
TI  - Estimation of the basic reproduction number of BSE: the intensity of transmission
      in British cattle.
AB  - The basic reproduction number, R0, of an infectious agent is a key factor
      determining the rate of spread and the proportion of the host population
      affected. We formulate a general mathematical framework to describe the
      transmission dynamics of long incubation period diseases with complex
      pathogenesis. This is used to derive expressions for R0 of bovine spongiform
      encephalopathy (BSE) in British cattle, and back-calculation methods are used to
      estimate R0 throughout the time-course of the BSE epidemic. We show that the 1988
      meat and bonemeal ban was effective in rapidly reducing R0 below 1, and
      demonstrate that this indicates that BSE will be unable to become endemic in the
      UK cattle population even when case clustering is taken into account. The
      analysis provides some insight into absolute infectiousness for bovine-to-bovine
      transmission, indicating maximally infectious animals may have infected up to 400
      animals each. The relationship between R0 and the early stages of the BSE
      epidemic and the requirements for additional research are also discussed.

PMID- 10081154
TI  - Good genes, oxidative stress and condition-dependent sexual signals.
AB  - The immune and the detoxication systems of animals are characterized by allelic
      polymorphisms, which underlie individual differences in ability to combat
      assaults from pathogens and toxic compounds. Previous studies have shown that
      females may improve offspring survival by selecting mates on the basis of sexual
      ornaments and signals that honestly reveal health. In many cases the expression
      of these ornaments appears to be particularly sensitive to oxidative stress.
      Activated immune and detoxication systems often generate oxidative stress by an
      extensive production of reactive metabolites and free radicals. Given that
      tolerance or resistance to toxic compounds and pathogens can be inherited, female
      choice should promote the evolution of male ornaments that reliably reveal the
      status of the bearers' level of oxidative stress. Hence, oxidative stress may be
      one important agent linking the expression of sexual ornaments to genetic
      variation in fitness-related traits, thus promoting the evolution of female mate
      choice and male sexual ornamentation, a controversial issue in evolutionary
      biology ever since Darwin.

PMID- 10081156
TI  - Acquired immunity and postnatal clinical protection in childhood cerebral
      malaria.
AB  - By analysing data on the age distribution of cerebral malaria among sites of
      different transmission intensities, we conclude that the most plausible
      explanation for the epidemiological patterns seen is that (i) cerebral malaria is
      caused by a distinct set of Plasmodium falciparum antigenic types; (ii) these
      antigenic types or 'CM strains' are very common and induce strong strain-specific
      immunity; and (iii) the postnatal period of protection against cerebral malaria
      is much longer than the period of protection against other forms of severe
      disease. The alternative hypothesis that cerebral malaria may be caused by any
      'strain' of P. falciparum is compatible with the data only if a single exposure
      is sufficient to protect against further episodes. This is not consistent with
      observations on the history of exposure of patients with cerebral malaria.
      Finally, it is clear that although the delayed peak in incidence of cerebral
      malaria (with age) can be generated by assuming that subsequent exposures carry a
      higher risk of disease, such an explanation is not compatible with the
      observation that severe disease rates are low among infants and young children in
      areas of high transmissibility.

PMID- 10081157
TI  - Increasing confidence in vergence as a cue to distance.
AB  - Multiple cues contribute to the visual perception of an object's distance from
      the observer. The manner in which the nervous system combines these various cues
      is of considerable interest. Although it is accepted that image cues play a
      significant role in distance perception, controversy exists regarding the use of
      kinaesthetic information about the eyes' state of convergence. We used a
      perturbation technique to explore the contribution of vergence to visually based
      distance estimates as a function of both fixation distance and the availability
      of retinal information. Our results show that the nervous system increases the
      weighting given to vergence as (i) fixation distance becomes closer; and (ii) the
      available retinal image cues decrease. We also identified the presence of a
      strong contraction bias when distance cues were studied in isolation, but we
      argue that such biases do not suggest that vergence provides an ineffectual
      signal for near-space perception.

PMID- 10081159
TI  - Evolutionary relationships of Metazoa within the eukaryotes based on molecular
      data from Porifera.
AB  - Recent molecular data provide strong support for the view that all metazoan
      phyla, including Porifera, are of monophyletic origin. The relationship of
      Metazoa, including the Porifera, to Plantae, Fungi and unicellular eukaryotes has
      only rarely been studied by using cDNAs coding for proteins. Sequence data from
      rDNA suggested a relationship of Porifera to unicellular eukaryotes
      (choanoflagellates). However, ultrastructural studies of choanocytes did not
      support these findings. In the present study, we compared amino acid sequences
      that are found in a variety of metazoans (including sponges) with those of
      Plantae, Fungi and unicellular eukaryotes, to obtain an answer to this question.
      We used the four sequences from 70 kDa heat-shock proteins, the serine-threonine
      kinase domain found in protein kinases, beta-tubulin and calmodulin. The latter
      two sequences were deduced from cDNAs, isolated from the sponge Geodia cydonium
      for the phylogenetic analyses presented. These revealed that the sponge molecules
      were grouped into the same branch as the Metazoa, which is statistically
      (significantly) separated from those branches that comprise the sequences from
      Fungi, Plantae and unicellular eukaryotes. From our molecular data it seems
      evident that the unicellular eukaryotes existed at an earlier stage of evolution,
      and the Plantae and especially the Fungi and the Metazoa only appeared later.

PMID- 10081162
TI  - Another set of responses and correlated responses to selection on age at
      reproduction in Drosophila melanogaster.
AB  - Ageing is the decline in survival probability and fertility later in adult life.
      It can evolve through mutation accumulation and pleiotropy. Artificial selection
      by age at reproduction is a useful method for detecting the effects of
      pleiotropy, and for producing lines that differ in their rate of ageing for
      further analysis. However, the approach has encountered difficulties from gene
      environment interaction and inadvertent selection. We have produced a new set of
      selection lines in Drosophila melanogaster, breeding from either 'young' or 'old'
      adults, and avoiding some of the difficulties present in previous studies.
      Breeding from older adults resulted in an evolutionary increase in survival but,
      contrary to all previous studies using this method, in no increase in late-life
      fertility. The increase in survival was accompanied by an evolutionary decline in
      fertility early in adult life, confirming the importance of pleiotropy in the
      evolution of ageing. Contrary to previous studies, there were no correlated
      responses to selection in the pre-adult period; development time, larval
      competitive ability and adult size achieved did not differ between the lines from
      the two selection regimes.

PMID- 10081163
TI  - Evolution of sperm size in nematodes: sperm competition favours larger sperm.
AB  - In the free-living rhabditid nematode Caenorhabditis elegans, sperm size is a
      determinant of sperm competitiveness. Larger sperm crawl faster and physically
      displace smaller sperm to take fertilization priority, but not without a cost:
      larger sperm are produced at a slower rate. Here, we investigate the evolution of
      sperm size in the family Rhabditidae by comparing sperm among 19 species, seven
      of which are hermaphroditic (self-fertile hermaphrodites and males), the rest
      being gonochoristic (females and males). We found that sperm size differed
      significantly with reproductive mode: males of gonochoristic species had
      significantly larger sperm than did males of the hermaphroditic species. Because
      males compose 50% of the populations of gonochoristic species but are rare in
      hermaphroditic species, the risk of male-male sperm competition is greater in
      gonochoristic species. Larger sperm have thus evolved in species with a greater
      risk of sperm competition. Our results support recent studies contending that
      sperm size may increase in response to sperm competition.

PMID- 10081164
TI  - Impact of market value on human mate choice decisions.
AB  - Mate choice strategies are a process of negotiation in which individuals make
      bids that are constrained by their status in the market place. Humans provide an
      unusual perspective on this because we can measure their explicitly expressed
      preferences before they are forced to make any choices. We use advertisements
      placed in newspaper personal columns to examine, first, the extent to which
      evolutionary considerations affect the level of competition (or market value)
      during the reproductively active period of people's lives and, second, the extent
      to which market value influences individual's willingness to make strong demands
      of prospective mates. We show that female market value is determined principally
      by women's fecundity (and, to a lesser extent, reproductive value), while male
      market value is determined by men's earning potential and the risk of future
      pairbond termination (the conjoint probability that the male will either die or
      divorce his partner during the next 20 years). We then show that these selection
      preferences strongly influence the levels of demands that men and women make of
      prospective partners (although older males tend to overestimate their market
      value).

PMID- 10081165
TI  - A minimal mechanism for bacterial pattern formation.
AB  - Colonies of Escherichia coli or Salmonella typhimurium form geometrically complex
      patterns when exposed to, or feeding on, intermediates of the tricarboxylic acid
      (TCA) cycle. In response to the TCA cycle intermediate, the bacteria secrete
      aspartate, a potent chemo-attractant. As a result, the cells form high-density
      aggregates arranged in striking regular patterns. The simplest are temporary
      spots formed in a liquid medium by both E. coli and S. typhimurium. In semi-solid
      medium S. typhimurium forms concentric rings arising from a low-density bacterial
      lawn, which are either continuous or spotted, whereas E. coli forms complex
      patterns arising from a dense swarm ring, including interdigitated spots (also
      called sunflower spirals), radial spots, radial stripes and chevrons. We present
      a mathematical model that captures all three of the pattern-forming processes
      experimentally observed in both E. coli and S. typhimurium, using a minimum of
      assumptions.

PMID- 10081166
TI  - [Programs of cooperation between internists and family physicians: a necessity].

PMID- 10081167
TI  - [The conduct of the family physician facing the elderly patient not seeking
      care].

PMID- 10081168
TI  - [Contraception: gypsy versus non-gypsy women].
AB  - OBJECTIVE: To find the contraceptive methods used or known by women of fertile
      age, and find differences between gypsy and non-gypsy women. DESIGN: Descriptive
      study. SETTING: Primary care centre in El Prat de Llobregat (Barcelona).
      PARTICIPANTS: Women of fertile age, who were sexually active and did not wish to
      become pregnant, and who attended the centre for any reason. MEASUREMENTS: From
      March to August 1997, a survey was conducted in which personal data, number of
      sexual contacts, parity, use and knowledge of contraceptive methods, if and where
      their method is monitored, and satisfaction with their method were asked.
      RESULTS: 186 non-gypsy and 126 gypsy women answered the survey. The gypsy women
      knew less about barrier contraception (diaphragm p < 0.0001); IUD p = 0.0003;
      spermicides p = 0.001), periodic abstention (p = 0.002) and definitive methods
      (vasectomy p < 0.0001; tubal occlusion p = 0.0004). The commonest method used by
      the gypsy women was coitus interruptus (p = 0.0002). Gypsy women asked for less
      contraceptive advice and had less monitoring of their method (p = 0.001). They
      had more pregnancies which led to a greater number of live children (p < 0.0001)
      and induced abortions (p = 0.01). They lived more often with their sexual partner
      (p = 0.0005). CONCLUSIONS: Gypsy women know about safe methods but do not use
      them. They ask less for contraceptive advice and have more induced abortions.
      There should be family planning programmes aimed at this group, whose cultural
      and family features are distinct.

PMID- 10081169
TI  - [Alternatives to population screening for breast cancer. Is the chance detection
      useful?].
AB  - OBJECTIVES: 1. To evaluate the characteristics of the demand, coverage and
      acceptability of random detection of breast cancer at a health centre (HC)
      between January 1995 and December 1996. 2. To describe the cases of breast cancer
      diagnosed since the setting up in 1988 of random demands for screening
      mammographies. DESIGN: Crossover study. SETTING: La Mina Primary Care Centre,
      Barcelona. PATIENTS: A sample of 340 women of a population of 2796 women between
      45 and 75 with a clinical history at the HC were studied. MEASUREMENTS AND MAIN
      RESULTS: The profile of women with neoplasms was: aged 59 +/- 8.5; 279 women
      attended, 273 medicine, 132 medicine and gynaecology, and 6 gynaecology.
      Mammographies requested were: 143 (118 through gynaecology, 12 medicine and 13
      outside the centre), which was 51% of women who attended and 42% of the sample.
      The reason for mammography was screening (129) and symptoms (14). Screening
      mammographies actually done (acceptance) were 116 out of 129 (90%). Sample
      coverage was 34% (116/340); and 42% of the women who attended (116/279). Most
      studied age-group was 50-64 (coverage 45%, n = 176). 11 cases of breast cancer
      were diagnosed: age 54.3 +/- 9.1; 1 in situ, 3 < 10 mm, 2 between 10 and 20 mm, 4
      > 20 mm, 1 without data. Diagnosis to treatment delay: 33.7 +/- 0 days. At time
      of writing 8 women were free of illness. CONCLUSIONS: Through random detection
      34% coverage was achieved with good acceptance. Most neoplasms are diagnosed in
      their early stages. The general practitioner should be more attentive to periodic
      requests for mammographies.

PMID- 10081170
TI  - [The variability in the care for diabetic and hypertensive patients as a function
      of the styles of a physician's practice].
AB  - OBJECTIVES: To analyse the variability of certain indicators of the procedure and
      outcome of medical care in the clinical records of diabetic and hypertense
      patients, and their relationship with the doctor's style of practice. DESIGN: An
      observational, descriptive study. SETTING: Seven health centres in the public
      network. PARTICIPANTS: 40 primary care doctors (all the doctors). MEASUREMENTS
      AND MAIN RESULTS: By means of stratified systematic random sampling, 20 clinical
      histories for each doctor were chosen (10 for patients diagnosed with diabetes
      mellitus and 10 with hypertension). The deviation ratio was used as the
      measurement of variability. Doctors' styles of medical practice were evaluated
      through the Australia questionnaire. Great variability was found in the frequency
      with which the different indicators of the two pathologies were recorded
      (deviation ratio: weight > 90.02% in DM, 81.37% in HT; height > 84.01% in DM,
      77.10% in HT), and in the absolute figures (patients with HT, wide variability in
      all outcome indicators; patients with DM, in last figures, total and HDL
      cholesterol, and HbA1c). The styles of practice were shown to be related to the
      frequency of appearance of some indicators in the clinical records and with the
      quality of particular outcome indicators. The age of the doctor correlated
      significantly, and negatively, with the recording of almost all the indicators
      and their quality. CONCLUSIONS: Variability of medical practice in the care of
      the chronically ill seen in primary care does exist. The use of clinical practice
      guides is emphasised.

PMID- 10081171
TI  - [The self-measurement of blood glucose and mean glycemias in patients with
      diabetes mellitus].
AB  - OBJECTIVE: To assess the influence that self-measurement of capillary blood
      glucose (SMBG) has on glucaemia control in patients with diabetes mellitus.
      DESIGN: Quasi-experimental before and after study. SETTING: Semi-urban health
      centre. PATIENTS: All diabetic patients, with at least two years of evolution,
      who used reactive strips for SMBG in 1996. MEASUREMENTS AND MAIN RESULTS: Mean
      values of base glucaemia in the SMBG study year were compared with those of the
      year before in 85 patients, 33 men and 52 women, with average age 62.38. Thirteen
      were type 1 and 72 type 2 diabetics, with a mean 15.61 years of evolution of the
      disease. A drop of -11.47 mg/dl (SD 44.32) was observed, which was significant (p
      < 0.05, CI 95%) in the overall results. In all the subgroups, except those
      treated with non-pharmacological measures, there were drops, ranging between 
      2.17 mg/dl and -17.01 mg/dl, which were significant in women, in patients with
      type 2 diabetes, in those who had received health education and in those treated
      with non-pharmacological measures plus insulin. CONCLUSIONS: Despite the
      limitations of this kind of study, our findings point towards a slightly better
      control of glucaemia levels in diabetic patients after SMBG. It is very doubtful
      whether it signifies any real improvement in managing the illness.

PMID- 10081172
TI  - [A thyroid function study in subjects with Down's syndrome].
AB  - OBJECTIVE: The main objective is to know the application degree of Spanish Health
      Program for Down Syndrome People respect to thyroid function. The secondary
      objective is to know the thyroid pathology in our population. DESIGN:
      Observational, descriptive and crossover study. SETTING: Primary care teams in
      collaboration with endocrinology services. PARTICIPANTS: Down syndrome people who
      lived in Albacete in 1993. MEASUREMENTS AND MAIN RESULTS: Survey to Down syndrome
      parents. Determination of thyroid hormones: T3, T4 and TSH, and thyroid
      autoantibodies (thyroglobulin and microsomal autoantibodies). RESULTS: 15.5% of
      our population had been done thyroid analysis before this study. The prevalence
      of thyroid pathology is 50.6% of the studied population. CONCLUSIONS: Due to low
      application of this program and its usefulness in thyroid pathology detection, we
      think that its should be used in primary care.

PMID- 10081173
TI  - [Validation of the tympanic thermometer in primary care].
AB  - OBJECTIVE: The aim of the study is to validate a tympanic thermometer (TT) use in
      primary care. PATIENTS AND METHODS: Validation study phase IV of the tympanic
      thermometer ThermoScan Pro LT. Measurements are compared to axillary temperature
      (AT) measured with a glass mercury thermometer. 412 subjects 6 months to 15 years
      old attended in primary care clinics were studied. Exclusion criteria were middle
      ear conditions, intense crying or sweating. The highest of the three measurements
      in each ear was used to calculate sensitivity and specificity of the TT and to
      analyse the concordance with AT. The impact of ambient temperature, age, gender,
      cerumen, presence of a febrile condition and the examiner on the results was
      assessed. RESULTS: Sensitivity of TT to detect fever (AT > 38 degrees C) was
      89.7% (95% IC: 81.8-97.5) and specificity 90.7% (95% IC: 87.7-93.7). As a mean TT
      measures 0.5 degree C higher than AT but there was a high dispersion of the data
      (-1.59-0.6 degrees C). Accuracy of TT was influenced by the sex of the patient (p
      = 0.029), examiner (p < 0.01), presence of a febrile condition (p < 0.01) and
      positioning of the patient (p = 0.026). Repeatability coefficient was 0.34 degree
      C for the right ear and 0.42 degree C for the left. CONCLUSION: The sensitivity
      of the TT to detect fever was adequate, though there was a poor concordance with
      AT and had an important variation among repeated measurements in the same ear.

PMID- 10081174
TI  - [The community orientation of primary care: a legacy of Prof. S. L. Kark (1911
      1998)].

PMID- 10081175
TI  - [Evacuative paracentesis at home].

PMID- 10081176
TI  - [A multidimensional study of the early risk factors associated with cognitive
      deterioration in patients over 65].

PMID- 10081177
TI  - [Terbinafine-induced ageusia and hyposmia].

PMID- 10081178
TI  - [The efficacy of a physiotherapy program in treating stress urinary incontinence
      in a rural female population, some nuances].

PMID- 10081179
TI  - [Economics and ethics in public health?].
AB  - The topic suggests a conflict between ethics and economy in medical care. It is
      often argued that today's welfare state in affluent societies with their social
      insurance systems makes it easier for the doctor to translate ethical demands
      into reality without being hampered by economic restrictions. Both doctors and
      patients took advantage of this system of medical care by mingling social
      guarantees for health with the doctor's income. Hence, medical expenses expanded
      rapidly, additionally promoted by technical progress in medicine. This entailed a
      proportionate increase in medical expenses in relation to personal income,
      especially wage income. Budgets of state authorities were streamlined or deficits
      became larger. This state of affairs was promoted further by mechanisms of
      distribution of national income in accordance with the slogan "less state, more
      market". While national income continued to grow, although at a slower rate, the
      number of jobless persons grew continually and thus also the social expenses,
      this was not due, as is usually assumed and pretended, to an economic crisis.
      Society and economy are facing a crisis of distribution of national income under
      conditions of technical progress as a job killer, making economic production more
      productive and efficient. Not taking into account the new challenge of social
      market economy--the German innovation in market economy creating the economic
      miracle after World War II--reforms of the system of medical care took place and
      are still continuing along market principles, particularly the latest German
      reform law leading to individual contracts between patients and their doctors in
      respect of cost charging. However, marketing principles promote economy in
      medicine, but they do not promote medical ethics. Further German guidelines for
      medical care should take stock of past experiences. There will be more
      competition in the "growing market of medical care" (private and public) and this
      will need--as economic experience has shown and economists have affirmed--new
      organisational devices to ensure better outcomes for the individual patient as a
      consumer and the doctors as suppliers. More responsibility should be given to the
      different suppliers of collective security in medical care (private or social
      systems of insurance). No individual patient as a mere consumer has a genuine
      chance in handling contracts with doctors carefully who are considered to be
      "gods in white" according to a popular German saying. These consumers have only a
      slight chance when arguing in courts of justice for the performance of contracts.
      Diagnosis and therapy, the system of doctors who treat members of statutory
      social insurance schemes (National Health general practitioners in the U.K.) and
      doctors as "free entrepreneurs" in the growing market of medical care should be
      separated due to the different rules of charging costs and offering medical care.
      "Classless medical care" does not have a better chance by applying market
      principles. The same is true for ethics versus economy. Doctors as "free
      entrepreneurs" must learn that markets will not guarantee reimbursement of costs
      but react to supply and demand. Hence, regulation of medical care by economic
      instruments creates better chances even for ethics in medical care against
      economy.

PMID- 10081180
TI  - [Expert assessment of medical treatment errors--a new responsibility for the
      medical service of health insurance].
AB  - During the past few years there has been an enormous increase of inquiries for
      medical certificates concerning suspected mistakes in medical treatment (medical
      malpractice). The profound changes of the social circumstances and the social law
      (e.g. section 66 SGB V) are responsible for this situation. The legal involvement
      of the "Gesetzliche Krankenversicherung" (GKV) and the "Medizinischer Dienst der
      Krankenversicherung" (MDK) into social legislation concerning the expert opinion
      are mentioned. The general development of the judgement of medical malpractice
      and its legal background, which bases on the contract between doctor and patient,
      is shown. As a practical example serves the description of the procedure of
      judging medical malpractice in the MDK. First statistical results, which have
      been developed since summer 1997 in Hamburg are presented. Some interesting
      tendencies are obvious: orthopedics and surgery are involved with more than 50%.
      "Characteristic mistakes in therapy" are the most important question for the
      expert opinion. Creating a medical certificate concerning medical malpractice
      takes about 6-12 weeks. This tendency is decreasing because of fast learning
      procedures, caused by the increasing demand of expert opinions. The medical
      judgement of medical malpractice will become one of the main tasks of the medical
      service in health insurance. The "MDK's" have to adapt to this change in tasks in
      medical, legal and organisation-technical respect, if they want to offer
      competent and up to date judgement in future times.

PMID- 10081181
TI  - [The "cost reimbursement" trial regulation in mandatory health insurance: results
      of a survey of participants].
AB  - Since 1994 seven substitution funds of the German statutory health insurance have
      offered their mandatorily insured members to choose cost reimbursement in place
      of benefits in kind for a limited testing period. Participants of the cost
      reimbursement arrangement are considered private patients and are billed
      accordingly. However, these bills are only in part reimbursed. This study
      investigates the expectations participants had with respect to the cost
      reimbursement arrangement as well as the experiences they made. For this purpose
      a survey among the participants was carried out using a self-administered
      questionnaire. Most of the 1390 respondents were satisfied with the cost
      reimbursement arrangement. Organisational, personal and medical advantages which
      the majority of participants expected were mostly fulfilled. Especially elderly
      members chose the cost reimbursement arrangement and often made the experience
      that their doctors spent more time talking to them. The necessary co-payments had
      hardly any impact on the positive judgment; most participants had an extra
      private insurance to close the gap of coverage. The results also show that
      transparency, control of costs and cost-consciousness of patients are improved by
      the cost reimbursement method. With respect to the preferences of the insured,
      the results of this study plead for keeping up the offer of cost reimbursement as
      an alternative to benefits in kind. However, the influence of sickness funds on
      the care process as well as the equity of care may be negatively affected.

PMID- 10081182
TI  - [School and vocational training, vocational status and myocardial infarct--a
      study with data of the mandatory health insurance].
AB  - We analysed whether indicators of social status (education and training,
      occupational grade) are associated with a first acute myocardial infarction (ICD
      410) between 1987 and 1996. Analyses were based on data from a statutory health
      insurance (Allgemeine Ortskrankenkasse) in Northrhine-Westfalia, Germany. 132,255
      men and women aged 30-69 years who were employed or were employed before
      retirement have been included in the investigation. The cumulated incidence of
      first myocardial infarction was 2.1% (n = 1938) among men and 0.8% (n = 327)
      among women. After adjustment for age and length of the observation period an
      increasing infarction risk with decreasing social status was observed in men.
      Respective odds ratios (OR) were 3.96 in the lowest educational and training
      group and 3.41 in the medium group as compared to men with the highest
      educational and training level. With regard to occupational grade respective odds
      ratios were 1.92 for the lowest (semi- and unskilled workers) and 1.73 for the
      medium group (skilled workers) compared to those with the highest grade level
      (skilled non-manuals, intermediate, professionals). Among women the risk was 1.47
      in the lowest educational and training group and 1.03 in the medium group. In
      semi- and unskilled women the OR was 1.58 and 1.67 in skilled women as compared
      to the highest occupational group. Although associations were observed between
      indicators of social status and risk of first myocardial infarction it is
      concluded that further research is needed due to the selection of the population
      under study with regard to education and occupational grade. Future research
      activities should concentrate on health insurances for skilled non-manual
      employees.

PMID- 10081183
TI  - [Increased debts and mental health].
AB  - Millions of people in industrialised countries are deeply involved in debts
      including two million households in Germany. Sociologists discuss the gap between
      modern consumers' wishes and disposable money. There is no research on the
      psychiatric impacts of debt and mental health. Bankruptcy is often caused by
      psychiatric difficulties. This is shown by case reports. Consequences for the
      individual and society are discussed, including the limits of freedom to
      indebtedness.

PMID- 10081184
TI  - [Income and smoking behavior in Germany--a secondary analysis of data from the
      1995 microcensus].
AB  - We investigated to what extent two major parameters of the economic situation,
      namely the household income and the type of the major source of income, are
      related to smoking behaviour. Study variables are current cigarette smoking and
      ex-smoking. Databasis is the Public Use File of the "Microcensus 1995", which is
      a representative survey for Germany, conducted under the auspices of the German
      Federal Statistical Bureau. Included in the analysis were 185,822 persons aged 18
      years and older. 30.9% of males and 18.2% of females are current smokers. 39% of
      males and 31.2% of females, who had been smokers at any time, stopped smoking.
      For persons aged 18 to 64 years, we observed strong income-related differences in
      the smoking prevalence. The higher the income the lower was the rate of smokers.
      Higher rates for ex-smokers were observed for persons older than 30 years, who
      had a high household income. For study subjects with a primary income based on
      unemployment or social welfare payments, we found for both sexes a remarkably
      higher smoking prevalence. Due to the fact that the underlying causes for the
      higher prevalence of smoking in the poorer segments of the population are not
      very well understood, it is rather difficult to establish a comprehensive
      prevention strategy for this high-risk population group.

PMID- 10081185
TI  - [Environmental studies of asymptomatic kindergarten children as carriers of
      enterohemorrhagic Escherichia coli (EHEC) in the Ammerland district].
AB  - The increase of serious EHEC diseases in the northwest Lower Saxony in summer
      1997 was accompanied by a lively discussion on the hazard represented by this
      pathogen which gained a large amount of media attention. The Lower Saxony Public
      Health Department initiated a study of this case in the Weser-Ems government
      district to investigate the spread of EHEC by children and their supervisors in
      kindergartens receiving certified raw milk supply. This established that there
      were ten kindergarten children in the Ammerland rural district who were
      asymptomatik EHEC carriers. The Local Public Health Department immediately
      carried out the necessary epidemic hygiene measures. First of all, control
      investigations were performed on the affected children, including environmental
      investigations on their families and contracts. The results of these
      investigations revealed the need to carry out additional environmental
      investigations in two kindegartens (follow-up investigations) as well as amongst
      employees in a hospital canteen. Within the families, a mother of an affected
      child was also identified as another asymptomatic EHEC carrier. However, the
      strains that were isolated reflected different serotypes. In total, the
      investigation of 337 people in contact with the eleven asymptomatic EHEC carriers
      did not confirm any person-to-person transmission--even though three of the
      kindergarten children shedding the organisms for 6-10 weeks attended the
      kindergartens for at least 4 weeks. No EHEC disease occurred in the communal
      facilities, neither were any positive cases identified by additional control
      investigations. The results indicate a probable lower rate of infectiousness by
      healthy EHEC carriers than was previously thought to be the case. Further studies
      are needed to decide if in future one should proceed on a case by case basis when
      considering the reauthorization of affected children and other people to enter
      communal facilities.

PMID- 10081186
TI  - [Effect of pets on human health: is there a correlation?].
AB  - Is there a Relationship? Despite an increasing number of studies devoted to the
      health benefits of interacting with pets, the empirical evidence of such an
      effect still remains weak. Many reports comparing health-related variables in pet
      owners and non-owners do not find significant differences. Some studies find a
      statistical correlation between pet ownership and better health, but they do not
      adequately demonstrate that the better health is a result of the pet. There is
      experimental evidence suggesting that the presence of animals is associated with
      a lowering of cardiovascular responses to stressors. Accordingly, pets could be
      used in the therapy of stress-related diseases. Nevertheless, no consistent
      clinical studies testing this hypothesis have been carried out. Moreover, neither
      evolutionary nor learning hypothesis for the observed decrease in cardiovascular
      reactivity have been tested till now. Research on the benefits of pet ownership
      still are in its preliminary steps. Further studies are needed for the
      understanding of the underlying psychological mechanisms of human/animal
      relationship and its therapeutic possibilities.

PMID- 10081187
TI  - [What is arterial hypertension? The balance of 50 years of research and rational
      therapy].
AB  - Over the past years the understanding of the pathogenesis of hypertension has
      increased considerably and many new antihypertensive drugs have been introduced.
      However, only a minority of patients are treated effectively and there is still
      concern about full potential for reversing coronary heart disease in hypertensive
      patients. It is necessary to distinguish between the treatment of a hypertensive
      population selected in prospective studies and a representative individual
      patient. The heterogeneity of the population, the individual variability of blood
      pressure and the rigid numerical criteria to define hypertension and normotension
      are the main sources of errors and false evaluations. In the future, ambulatory
      blood pressure measurement devices and better designed trials that conform better
      to clinical practice will be introduced. Moreover, initiation of antihypertensive
      treatment, choice of drugs and their doses and combinations should not be based
      on the number of millimetres of mercury but rather on a careful evaluation of the
      pathogenetic mechanism and risk factors, since hypertension is not an isolated
      elevation of blood pressure; it rather is a metabolic impairment of tissue
      function at the cellular level, genetically conditioned and triggered by various
      endogenous and external factors.

PMID- 10081188
TI  - [Differential diagnosis of expansive lesions in the sellar region using magnetic
      resonance imaging].
AB  - Diagnosis of the type of expansive pathological lesion in the sellar region is of
      fundamental importance. Magnetic resonance is an imaging method which proved
      dominant and provides most information from the sellar region. Although no sign
      in the MR image is quite specific for a certain lesion, the substrate diagnosis
      can be assessed with a considerable probability. The presented paper gives an
      account of the authors experience supplemented by literature on the problem.

PMID- 10081189
TI  - [Direct detection of mutations in the LDL receptor gene in patients with familial
      hypercholesterolemia].
AB  - BACKGROUND: Familial hypercholesterolemia is one of the most frequent hereditary
      metabolic diseases. As a result of the functional disorder of the molecule of the
      LDL receptor LDL cholesterol is not sufficiently eliminated from the blood stream
      and exerts an atherogenic effect. The objective of the study was to introduce
      direct detection of mutations in the gene for the LDL receptor and characterize
      the spectrum of mutations in the Czech population. METHODS AND RESULTS: The
      authors analyzed a group of 84 unrelated patients where on the basis of clinical
      and biochemical criteria the diagnosis of FH was established. From the group 12
      patients were eliminated (14.3%) where a mutation 3500 in the gene for
      apolipoprotein (apo) B-100 was detected. This mutation is most frequently the
      cause of a familial defect of apo B-100 (FDB), which cannot be differentiated
      clinically or biochemically from FH. In the LDL receptor gene a total of 11
      mutations were found in 14 unrelated patients (16.7%), incl. 7 mutations not
      described hitherto. CONCLUSIONS: This is the first systematic characteristic of
      the spectrum of mutations in the LDL receptor gene in the Czech population.
      Molecular genetic analysis of the gene for the LDL receptor in affected families
      can contribute towards early assessment of the diagnosis of FH and thus to
      prevention of life threatening cardiovascular episodes in asymptomatic subjects.

PMID- 10081190
TI  - [The effect of age on levels of magnesium and creatinine in the urine].
AB  - BACKGROUND: The concentration of magnesium in urine reflects its intake from food
      resources. The main regulatory mechanism of magnesium homeostasis is the kidney
      filtration-absorption process. So far the reference values are not known of the
      magnesium concentration in urine in dependence on age and sex for the normal
      population. Therefore, we focused on investigating these problems in a randomly
      selected sample of persons of both sexes, aged 1-93 years. Beside magnesiuria we
      also assessed creatininuria. METHODS AND RESULTS: The selection of 2715 persons
      of both sexes aged from one to ninety three years was made by the random
      selection method. As we have found no statistically significant difference
      between men and women as regards concentrations of magnesium and creatinine in
      urine, the evaluated groups include persons of both sexes. The whole is divided
      into age groups as follows: children 1 year (n = 24), 2 years (n = 15), 4 years
      (n = 18), 6 years (n = 378), 10 years (n = 424), 13 years (n = 416), and adults
      18-35 years (n = 396), 36-49 years (n = 482), 50-65 years (n = 453), 66-75 years
      (n = 53), 76-85 years (n = 42), 86-93 years (n = 14). In the morning urine after
      twelve-hour fasting we determined the concentration of magnesium and creatinine
      be using Merck Vitalab Eclipse apparatus. The concentration of magnesium in urine
      rises from 3.37 +/- 0.28 mmol/l at 1 years to the top value 6.64 +/- 0.58 mmol/l
      (p < 0.001) at 4 years, and since this age it is continuously dwindling to the
      value 2.35 +/- 0.17 mmol/l (p < 0.001) at the age of 93 years. The creatinine
      concentration in urine rises from 2.47 +/- 0.30 mmol/l at the age of one year to
      15.33 +/- 0.36 mmol/l (p < 0.001) in the age group 18-35 years, and further it
      goes down with age to the value 6.23 +/- 0.99 mmol/l (p < 0.001) at 93 years. The
      highest ratio of the urine concentrations of magnesium and creatinine 1.98 +/-
      0.32 is at the age of 2 years, and then it is continuously subsiding to 0.41 +/-
      0.15 (p < 0.001) at the age range 66-75 years. CONCLUSIONS: When evaluating the
      magnesium concentration in urine as the index of a sufficient supply of organism
      with this ion, and also in various studies of metabolism, it is essential to
      consider the patient's age. The ratio of cocentrations in urine of magnesium and
      creatinine does not improve the meaningfulness of magnesium analysis.

PMID- 10081191
TI  - [Immunohistochemistry of a biopsy of an allotransplanted kidney].
AB  - BACKGROUND: Cellular rejection infiltration of the interstitium is the basic
      histological finding in biopsies of transplanted kidneys, and leukostasis in the
      muscular arteries and glomeruli is an important sign of exacerbating rejection.
      For better understanding and more accurate interpretation the authors used
      immunohistochemistry. METHODS AND RESULTS: The authors examined 282 tissue
      specimens from 208 grafts using the two- or three-step immunoenzyme method with
      28 mono- or polyclonal antibodies specific for a series of differentiation and
      activation leukocytic antigens, adhesion molecules and selected cytokines. In the
      compact component of the rejection infiltrate CD4+ lymphocytes with expression of
      CD 45 RA antigen predominated while in the disperse component there were mostly
      macrophages (CD68, 14, 11b); their number correlated significantly with the
      parenchymatous damage, similarly as intraarterial and glomerular accumulation.
      The disperse infiltrate and adherent cells expressed CD45 RO (rarely CD25) and
      integrin molecules of the series CD11 and CD49 CD57+ lymphocytes penetrated into
      the tubules but did not accumulate in the blood vessels. As to adhesive molecules
      of the "Ig superfamily", CD106 (VCAM-1) was more important than CD54 (ICAM-1) and
      its arterial and mesangial expression correlated with the rejection damage.
      Evidence of cytokines (IL1, IL2, TNF alpha, beta) did provide neither unequivocal
      results nor correlations. CONCLUSIONS: Immunohistochemistry improves considerably
      the accuracy of bioptic evaluation of rejection nephropathy and some antigens
      (e.g., CD68, CD14, CD45 RO., CD57, CD106) are suitable for diagnostic practice.
      With their aid it is easier to evaluate the activity of rejection, assess the
      probability of vascular lesions in specimens without affected vessels and detect
      more sensitively intravascular stasis and adhesion of leukocytes.

PMID- 10081192
TI  - Thank you Luther Christman.

PMID- 10081193
TI  - Christman and nurse execs.

PMID- 10081194
TI  - NP program missing content in practice.

PMID- 10081195
TI  - Nursing missing in action.

PMID- 10081196
TI  - Troubled by Christman.

PMID- 10081197
TI  - ND makes sense for APNs.

PMID- 10081198
TI  - Doctoral entry unrealistic.

PMID- 10081199
TI  - Diversity requires nursing AA degree.

PMID- 10081200
TI  - Need religion and numbers.

PMID- 10081201
TI  - Too much emphasis on function and methods, too little on care and cure.

PMID- 10081202
TI  - First-rate scholarship by LeVasseur.

PMID- 10081205
TI  - Mayer on ER violence and study findings.

PMID- 10081203
TI  - Welcomes language translation.

PMID- 10081206
TI  - Access to health care.
AB  - PURPOSE: To describe and analyze conceptual and operational definitions of health
      care access for future nursing theory, practice, and policy. Access to health
      care is a major health policy concern. However, the elements of access to care
      are not well understood. As a result, how access is addressed is often
      inconsistent and unclear. ORGANIZING CONSTRUCT: Walker and Avant's framework for
      concept analysis. SOURCES: Published literature in nursing and health services
      from the 1960s to the 1990s. The analysis was done in 1997 for this integrative
      review of nursing and nonnursing literature. METHODS: Integrative literature
      review in 1997. FINDINGS: Access is a complex idea defined in many ways. One of
      the most comprehensive definitions of access is by the World Health Organization
      (WHO). Multidimensional barriers and facilitators to access vary by community and
      country. CONCLUSIONS: Societies may define access differently at different stages
      of development. Scales to measure some dimensions of access are available;
      however, newer and better measures are needed and are being developed and tested.
      Data on each of the dimensions are needed for comprehensive assessment of access
      to health care in all countries at all stages of development.

PMID- 10081207
TI  - Potential for abusive parenting by rural mothers with low-birth-weight children.
AB  - PURPOSE: To describe factors influencing the potential for abusive parenting by
      rural mothers of low-birth-weight children (< 2,500 gm). Low-birth-weight (LBW)
      children are at risk for child abuse. However, little is known about the added
      risks created for these children by rural residency. DESIGN: Data for this
      descriptive and exploratory study were collected using a cross-sectional design.
      A convenience sample of 48 rural mothers delivering LBW children participated in
      1994. METHODS: In-home interviews were conducted using structured questionnaires
      to assess mothers' everyday stressors, depressive symptoms, social resources, and
      child abuse potential. FINDINGS: The prevalence of high depressive symptoms among
      the mothers was 54%. Higher everyday stressors and less functional social support
      predicted greater depressive symptoms. Everyday stressors had a direct effect on
      the mothers' potential for child abuse and an indirect effect via maternal
      depressive symptoms. CONCLUSIONS: Rural mothers of LBW children are at risk for
      abusive parenting. Health care providers should pay particular attention to the
      mental health of mothers living in rural, isolated areas. Assistance with
      mobilization of community resources, including social support and child care, may
      provide needed help for these mothers to improve parenting and thus child health
      outcomes.

PMID- 10081208
TI  - Questioning the quality of maternal caregiving during home visiting.
AB  - PURPOSE: To formulate theory that will provide a meaningful framework for
      practice and for studies examining the efficacy of maternal-child home visits.
      DESIGN: Field research, over a period of 8 months, 1995-1996, conducted with one
      nurse employed by a visiting nurse association in rural New England. A total of
      53 home visits were observed; documents and records were reviewed. METHODS: Data
      collection, field-note recording, and analysis were simultaneous. Informal
      interviewing and observation of the key nurse participant throughout the day
      focused on her intentions, actions, and meanings as she anticipated, enacted, or
      reflected on her visits. Client-nurse interaction and client characteristics were
      described and interpreted. Analysis focused on the nurse's home visits and the
      consequences of these visits. FINDINGS: The nurse conducted a specific type of
      home visit, identified as "child-focused," in three patterns: single, short-, and
      long-term. The short-term pattern, labeled "questioning the quality of maternal
      caregiving," is described in this article. The nurse minimally questioned and
      then confirmed the quality of maternal caregiving during some visits, while she
      seriously questioned and then continuously doubted the quality of caregiving in
      others. The categories of potential consequences of these visits were maternal,
      child, interactive, and environmental. CONCLUSIONS: Future research should
      address the most effective processes for working with families when nurses doubt
      the quality of maternal caregiving. Field research was helpful in developing a
      beginning typology of maternal-child home visits, in understanding practice, and
      as a basis for further research examining the efficacy of maternal-child home
      visits.

PMID- 10081209
TI  - Religious faith in Mexican-American families dealing with chronic childhood
      illness.
AB  - PURPOSE: To explore Mexican-American family experiences with chronic childhood
      illness, from the perspective of parents, and report findings about the influence
      of religious faith on families' spiritual and secular responses to illness.
      Mexican-Americans are often characterized as religious, fatalistic, and passive,
      but families' perceptions of the consequences of their daily faith and its
      meaning in the face of chronic childhood illness is not well understood. DESIGN:
      Descriptive. The sample included 25 parents from 19 families living with children
      with a variety of chronic conditions. Data were collected in 1995-1996. METHODS:
      Interpretive, using symbolic interaction as the framework, and in-depth
      interviewing for data collection. FINDINGS: Parents professed a variety of
      beliefs and devotional practices. Six unifying dimensions of religious faith were
      related to parental caretaking and decision making for the family: (a) God
      determined the outcome of the child's illness, (b) God and health care for the
      child were closely linked, (c) parents took an active role in facilitating God's
      will, (d) families had obligations to God, (e) intercession with God by others
      was often sought by or offered to the family, and (f) faith encouraged optimism.
      CONCLUSIONS: Families were not fatalistic in the sense of feeling outcomes were
      predetermined and unalterable. Family members took spiritual and secular actions
      to assure the best possible familial and professional care for their child and
      sought to influence God's good will on behalf of the child and family.

PMID- 10081210
TI  - Developing a clinical doctorate to prepare nurses for advanced practice at the
      University of Tennessee, Memphis.

PMID- 10081211
TI  - Genuine professional doctor of public health the world needs.

PMID- 10081212
TI  - Defining and measuring fatigue.
AB  - In response to a long history of problems with defining and measuring fatigue,
      the University of Kansas School of Nursing established a Center for Biobehavioral
      Studies of Fatigue Management to facilitate the study of fatigue in diverse
      populations. The purpose of this article is to review past efforts to define and
      measure fatigue and the conceptual problems relevant to currently used measures
      of fatigue. Several distinct characteristics and corresponding measures of
      fatigue are identified and a definition and framework for the study of fatigue
      are discussed. Future research on fatigue must attend to the conceptual
      distinctions among various measures and the measures of fatigue most appropriate
      to the goals of a study.

PMID- 10081213
TI  - Report of a state-of-the-knowledge conference on U. S. nursing certification.
      ONCC Research Committee and Executive Staff. U. S. Oncology Nursing Certification
      Corporation.
AB  - PURPOSE: To describe the problems discussed, consensus established, and
      recommendations made during a "state of the knowledge" conference on nursing
      certification hosted by the Oncology Nursing Certification Corporation (ONCC),
      April 1996. ONCC planned the conference after finding little empiric data in the
      literature to support the value of nursing certification and after recognizing
      that consensus was lacking regarding several critical questions related to
      certification. SOURCES: Representatives of 24 specialty nursing certification
      organizations participated in the 3-day conference. METHODS: Through formal
      presentations and small groups, participants identified unresolved issues and
      areas of consensus, then strategized ways to address questions and problems.
      RESULTS: This historic conference identified problems that require proactive
      responses and solutions by organizations involved in nursing certification.
      Unresolved issues included the lack of standardization of basic certification
      procedures, the means of evaluating continued competency, and questions regarding
      the relationship between certification and patient outcomes. Development of a
      nursing multispecialty research council was proposed and has since been
      established under the leadership of the American Nurses Credentialing Center.
      CONCLUSIONS: The conference was a successful way to unite specialties in nursing.
      Of high priority is the need to validate that certification positively affects
      patient outcomes. Until this can be shown, it will be difficult to persuade
      employers and payers that nursing certification should be a workplace
      requirement.

PMID- 10081214
TI  - Stories of growing up amid violence by refugee children of war and children of
      battered women living in Canada.
AB  - PURPOSE: To explore how two groups of children who grew up amid violence "make
      sense" of their experience. As violence has become a common element of some
      societies, growing numbers of children have been forced to live in dangerous
      environments. Although considerable research has been conducted with children who
      are abused or neglected, the needs of those who witness violence have been
      largely overlooked. DESIGN: Critical narrative and descriptive. Data were
      collected, 1995-1996, in Canada from a convenience sample of 16 refugee children
      of war and 16 children of battered women. METHODS: Participants were asked open
      ended questions about the violence in their lives, their feelings about what
      occurred, their thoughts about the reasons for violence, and their ways of
      surviving and growing. Common themes were identified and validated. FINDINGS:
      Despite differences in the children's stories, many parallels were evident. Both
      groups of youngsters endured pain, suffering, and feelings of betrayal. Both used
      creative strategies to survive. The way the children endured growing up amid
      violence was mediated by social, political, and cultural constructions of
      violence. Because these meanings were unique, violence was experienced in several
      ways. CONCLUSIONS: Although the children showed remarkable strength and insight,
      they face many challenges. Despite a common perception that children are unable
      to talk about deeply troubling experiences, this research demonstrated that
      children not only want to discuss their experience, but also welcome the
      opportunity to do so.

PMID- 10081215
TI  - Nursing practice theory of exercise as self-care.
AB  - Exercise reduces the risk of cardiovascular disease (CVD) and promotes health.
      Most people in the United States do not exercise regularly. Nurses can promote
      exercise using the proposed theory as a guide. This theory of exercise was
      developed through triangulation of Orem's self-care deficit theory of nursing,
      the transtheoretical model of exercise behavior, and characteristics of a
      population at risk for CVD. Practice theory and use of individual constructs were
      reviewed, revised, and validated by experts familiar with the organizing
      constructs. Future testing and evaluation of practice theory as a guide for
      promoting exercise is planned.

PMID- 10081216
TI  - Experiencing control in caregiving.
AB  - PURPOSE: To describe the experience of control as perceived by family caregivers
      who care for relatives with dementia to determine how caregivers manage care at
      home. The ability to manage care effectively at home is important because of the
      rise in the number of family caregivers. DESIGN: Descriptive using secondary
      analysis of qualitative data. The sample was 21 family caregivers of relatives
      with dementia, 4 men and 17 women, from one medium-sized city in Canada. METHODS:
      Grounded-theory methods were used for the secondary analysis of data completed in
      1997 from a previous 1995 study of caregivers. RESULTS: The experience of control
      was related to how caregivers managed or coped with their caregiving situations.
      The dimensions of control were characterized as either "maintaining control" or
      as "lacking control" with each dimension relating to caregivers' beliefs about
      caregiving. CONCLUSIONS: Results of this study can help nurses intervene more
      effectively with family caregivers by recognizing how caregivers manage and
      whether they need assistance to continue to provide care. The proposed model is a
      starting point for further research on control and coping; it also provides
      direction for practice.

PMID- 10081217
TI  - Comfort in labor and midwifery art.
AB  - PURPOSE: To examine the phenomenon of comfort in the context of childbirth.
      Enhancement of comfort for laboring women is a valued outcome of nursing and
      midwifery care. Interventions that increase comfort during labor support a
      woman's effort to participate more fully in the birth thereby keeping her more
      aware of her body, emotions, and experience. ORGANIZING CONSTRUCT: The concept of
      comfort is analyzed and defined in the context of laboring women. Comfort studied
      from a feminist perspective is suggested. SOURCES: A literature review of
      nursing, midwifery, and medical texts from the 1920s to 1998 provides information
      about labor, pain in labor, and goals of providers caring for laboring women.
      Research articles focusing on comfort are identified as they relate to the
      concept of comfort in labor. Writings of contemporary feminist authors provided
      the ideas for designing the study of comfort from a feminist perspective.
      METHODS: To develop a theory of comfort during labor, early nursing and midwifery
      texts were searched to identify goals of care. The meaning of comfort was
      analyzed from the early 1920s to the present by concept analysis. Validation of
      findings was sought from publications on comfort research. FINDINGS: Comfort can
      exist in spite of great pain and nurses and midwives may be able to assist
      laboring women to achieve a level of comfort during labor. Intervening to promote
      the comfort of laboring women can empower these women during birthing.
      CONCLUSIONS: For clinicians caring for birthing women, particularly midwives,
      promotion of comfort is a high priority. Increasing comfort can redefine the
      meaning of pain in childbirth. Increasing comfort may create a decreased need for
      medical interventions and lower costs.

PMID- 10081218
TI  - Mothers' responses to care given by male nursing students during and after birth.
AB  - PURPOSE: To describe the rationale maternity patients use in determining whether
      to accept care by a male student nurse. Information about the activities that
      women are comfortable having male nursing students perform is inconsistent and
      the reasons for women's comfort or discomfort are unclear. Furthermore, little is
      known about what factors patients consider when assigned a male nursing student.
      Yet, knowledge of such factors can enhance understanding and guide the selection
      of students in maternity units. DESIGN: Focused ethnography using a purposive
      convenience sample of 32 women, aged 20 to 40 years, who spoke English, and who
      had given birth to normal newborns in one small community hospital in the mid
      Atlantic region of the United States. Patients were excluded if they or their
      infants were in an unstable physical or mental condition. The study was conducted
      in 1995. METHODS: The women were interviewed using a semi-structured format.
      FINDINGS: Data from participants pertained to personal and contextual factors.
      Personal factors were perception of postpartum self and personal feelings.
      Contextual factors were student characteristics, establishment of relationships,
      nursing care activities, and partner viewpoint. CONCLUSIONS: Women during and
      after giving birth have definite thoughts about male student nurses caring for
      them. Nurse educators should consider these when assigning men. Educators should
      encourage professionalism and competence in their students.

PMID- 10081219
TI  - Maintaining client safety and scientific integrity in research with battered
      women.
AB  - PURPOSE: To increase awareness of considerations of privacy and safety as well as
      the potential for scientific misconduct in research with battered women and other
      groups especially vulnerable to these concerns. Research with such vulnerable
      populations demands consideration of privacy and safety of participants in order
      to limit any potentially negative consequences while also ensuring scientific
      integrity. ORGANIZING FRAMEWORK: Maintaining scientific integrity and protecting
      vulnerable groups are important but potentially contradictory. Battered women are
      the examples to illustrate instances of conflict in which protecting participants
      may undermine scientific integrity. SOURCES: Literature on scientific integrity
      and misconduct, battered women, and vulnerable populations, and socially
      sensitive topics from nursing, other biomedical and social sciences, and the U.S.
      Public Health Service, 1978-1998. METHOD: Integrative literature review.
      FINDINGS: Conducting research with battered women in an ethically responsible
      manner that maintains scientific integrity without compromising advocacy or
      safety is possible when scientists are aware of potential conflicts and methods
      to ensure integrity. CONCLUSIONS: Nurses frequently do research with vulnerable
      groups such as battered women. Being proactive can help promote scientific
      integrity, avoid scientific misconduct, and decrease negative outcomes.

PMID- 10081220
TI  - Complement genetics: biological implications of polymorphisms and deficiencies.

PMID- 10081221
TI  - New perspectives on immunobiology and immunotherapy of melanoma.

PMID- 10081222
TI  - On the intrathymic intercellular transfer of self-determinants.

PMID- 10081223
TI  - Genetic risk factors for autoimmune diseases.

PMID- 10081224
TI  - Transcriptional enhancers and the evolution of the IgH locus.

PMID- 10081225
TI  - Does properdin crosslink the cellular and the humoral immune response?

PMID- 10081226
TI  - A new taxonomy of mammalian MHC class I molecules.

PMID- 10081227
TI  - Are dendritic cells the key to liver transplant tolerance?

PMID- 10081228
TI  - A kinetic differentiation model for the action of altered TCR ligands.

PMID- 10081229
TI  - The pathogenesis of psoriasis: immunological facts and speculations.

PMID- 10081230
TI  - The Fas counterattack: cancer as a site of immune privilege.

PMID- 10081231
TI  - Dual origin of lymphocytes?

PMID- 10081232
TI  - Microbe exposure, innate immunity and autoimmunity.

PMID- 10081233
TI  - A phylogenetic analysis of the relationship between sub-adult mortality and mode
      of subsistence.
AB  - The hypothesis that measures of sub-adult mortality rates in natural fertility
      populations are associated with subsistence practices in a selected cross
      cultural sample (n = 39) was tested. After controlling for both distance from the
      equator and the general likelihood of cultural similarities between genetically
      closely related cultures using phylogenetic comparative methods, it was found
      that dependence on extractive modes of subsistence (hunting, gathering and
      fishing) was a significant positive correlated of total child mortality (15q0).
      Both increases in dependence on foraging and permanent settlement were associated
      with increases in child mortality between pairs of historically related cultures.
      The results indicated little association between infant mortality (1q0) and
      either dependence on foraging or settlement.

PMID- 10081234
TI  - Preference for children and subsequent fertility in Matlab: does wife-husband
      agreement matter?
AB  - This study examines wife-husband preference for children and subsequent fertility
      for a period of 5 years in the treatment and comparison areas of Matlab,
      Bangladesh. The two data sets used were: the In-depth Survey (1984) and the
      Demographic Surveillance System (1984-89). In the case of wives' preferences for
      children, subsequent childbearing was 13.8% higher than desired in the treatment
      area and 44.7% higher than desired in the comparison area. After controlling for
      all variables in the model, the likelihood of giving birth was 1.78 times higher
      for wives who wanted no more children, but whose husbands did want more, compared
      with couples where neither husband nor wife wanted more children. For couples
      where the wife wanted more, but the husband did not want more children, the
      likelihood of giving birth was 0.63 times that of couples where both the husband
      and wife wanted more children. This finding suggests that to enhance the decline
      in fertility in these two areas of Matlab, it will be necessary to motivate both
      wives and husbands to cease childbearing.

PMID- 10081235
TI  - Nature, nurture and first sexual intercourse in the USA: fitting behavioural
      genetic models to NLSY kinship data.
AB  - Fisher (1930) presented both theoretical and empirical results concerning genetic
      influences on fertility. Since then, only sparse research has been done on the
      genetics of fertility, although more sophisticated methodogy and data now exist
      than were available to Fisher. This paper presents a behavioural genetic analysis
      of age at first intercourse, accounting for genetic, shared environmental, and
      selected non-shared environmental influences. The data came from the nationally
      representative National Longitudinal Survey of Youth (NLSY). A newly developed
      kinship linking procedure was used that identifies links for cousins, half
      siblings, full-siblings and twins in the NLSY. The results suggest a genetic
      influence in the overall dataset, and also among whites and in male-male and
      opposite-sex pairs. Genetic influences were extremely small or non-existent for
      blacks and for female-female pairs. Shared environmental influences were small
      for most subsets of the data, but moderate for female-female pairs. Two specific
      non-shared environmental influences--self-esteem and locus of control--were ruled
      out as accounting for any meaningful variance, although other general sources of
      non-shared environmental influence appear potentially important. Analysis of
      selected samples from upper and lower tails suggested that genetic influences are
      important in accounting for both early and late non-virginity. These findings are
      consistent with work reported by Miller et al. (1999), who used molecular genetic
      methods. Generally, these findings support the existence of genetic influences
      and implicate non-shared environmental influences as being important determinants
      of the timing of loss of virginity among US adolescents and young adults.

PMID- 10081236
TI  - Dopamine receptor genes are associated with age at first sexual intercourse.
AB  - The dopaminergic system in the brain seems to play an important role in the
      regulation of sexual behaviour. The relationship between genes for the D1, D2 and
      D4 dopamine receptors and age at first sexual intercourse (AFSI) was examined in
      a sample of 414 non-Hispanic, European-American men and women. A significant
      association was observed between a DRD2 allele and AFSI and an even stronger
      association when the DRD2 allele was interacted with a DRD1 allele. A constrained
      regression model was constructed predicting AFSI using sex and a group of nine
      psychosocial variables as predictors. Adding the DRD2 and the DRD2-by-DRD1
      predictors to this model increased the explained variance by 23 and 55%,
      respectively. Although these findings suggest a stronger association among males
      than among females, further research will be necessary to clarify this question,
      as well as to establish whether the observed association holds in other
      racial/ethnic groups.

PMID- 10081237
TI  - Effects of the status of women on the first-birth interval in Indian urban
      society.
AB  - The status of women, which is relative and multidimensional, has an important
      bearing on any long-term reduction in fertility. In Indian society, where
      cohabitation and childbearing are socially sanctioned only after marriage, the
      length of the first-birth interval affects the completed family size by
      influencing the spacing and childbearing pattern of a family. This study examines
      the influence of certain aspects of the status of married women--education,
      employment, role in family decision making, and age at marriage--along with three
      socioeconomic variables--per capita income of the family, social position of the
      household, and the caste system--on the duration of the first-birth interval in
      an urban Hindu society of the north-east Indian state of Assam. The data were
      analysed by applying life table and hazard regression techniques. The results
      indicate that a female's age at marriage, education, current age, role in
      decision making, and the per capita income of the household are the main
      covariates that strongly influence the length of the first-birth interval of
      Hindu females of urban Assam. Of all the covariates studied, a female's education
      appears to be a key mediating factor, through its influence on her probability of
      employment outside the home and thereby an earned income and on her role in
      family decision making. Unlike other Indian communities, the effect of the caste
      system does not have a significant effect on first-birth timing in this urban
      Hindu society.

PMID- 10081238
TI  - Daily time budgets of long-distance commuting workers in Tokyo megalopolis.
AB  - In Tokyo Megalopolis, long-distance commuting between residences in the suburbs
      and work places in the centre of the city was examined. Using a questionnaire,
      heads of household in two suburbs were asked about the influences of long
      commuting hours on their daily time budgets. The results showed that on workdays,
      the workers who spent longer commuting rose and left home for work earlier, and
      came back home and retired later; accordingly, both time spent on in-home
      activities on workdays and hours slept on the day before a workday were shorter.
      Comparison of time budgets between the subjects who work 5 and 6 days per week
      revealed more vulnerable influences of long commuting hours in the former than
      the latter. The expected health consequences of these findings are discussed from
      a biosocial/human ecological viewpoint.

PMID- 10081239
TI  - Mosquito avoidance and bed net use in the Greater Accra Region, Ghana.
AB  - Qualitative research and cross-sectional survey methods were used in a study
      conducted in rural and urban areas of the Greater Accra Region, Ghana, to explore
      people's understanding of the cause of malaria and patterns of mosquito
      avoidance, in particular bed net ownership and use. The study indicated far
      higher bed net ownership and use in rural than urban areas, which was related
      partly to perceived affordability and partly to the different contexts of and
      reasons for avoiding mosquitoes. Knowledge of an association between mosquitoes
      and malaria, the most common cause of illness in both areas, was related to
      residence but not to literacy or formal education, and this knowledge did not
      predict bed net use. The paper points to the complexity of social and personal
      factors implicated in behavioural interventions for malaria control, and
      questions behavioural models that assume a linear relationship between knowledge
      and practice.

PMID- 10081240
TI  - Marriage structure and contraception in Niger.
AB  - Analysis of the 1992 Niger Demographic and Health Survey showed that although
      roughly two-thirds of both polygamous and monogamous women approve of birth
      control, polygamous wives are less likely than monogamous wives to discuss family
      size or birth control with their husband or to plan on using birth control. The
      study suggests that characteristics of polygamous couples have caused polygamous
      women to be more resistant to birth control use than monogamous women. The
      polygamous women tended to be married to older men who had not gone to primary
      school and who desired more children than monogamous husbands. The influence of
      marital structure is not significantly associated with intention to use birth
      control when the husband's age and the wife's ideal number of children were
      controlled for in the multivariate logistic regression model suggesting that
      background social factors may be more influential. In fact, educational level and
      age at first marriage were significantly associated with attitudes towards birth
      control and also with marital structure.

PMID- 10081241
TI  - Ethnicity and contraceptive use in sub-Saharan Africa: the case of Ghana.
AB  - Using a sub-sample of ever-married women from the 1993 Ghana Demographic and
      Health Survey (GDHS), this study examines differentials in contraceptive use in
      six cultural groups: Ga-Adangbe, Twi, Fante/other Akans, Ewe, Guan/others and
      Mole-Dagbani. Multivariate analysis is used to explore whether reported ethnic
      differentials in contraceptive use can be attributed to ethnicity or to other
      characteristics that distinguish the ethnic groups. Overall, the findings are
      generally more consistent with the 'characteristics' hypothesis, because
      contraceptive use differentials by ethnic group is accounted for by differences
      in socioeconomic and demographic characteristics of these women. However, for the
      Fante/other Akans, even after the necessary controls, ethnicity continued to
      emerge as a significant determinant of contraceptive use. Programmatic
      implications of these results are discussed.

PMID- 10081242
TI  - Consanguineous marriage and differentials in age at marriage, contraceptive use
      and fertility in Pakistan.
AB  - Fertility rates in Pakistan have remained consistently high over the past three
      decades. While numerous studies have examined sociodemographic determinants, the
      role of biological factors, and particularly consanguinity, has received little
      attention, even though marriage between close biological relatives continues to
      be the norm in Pakistan. Reproductive behaviour among women in consanguineous
      (first cousin) and non-consanguineous unions was compared, using data from a 1995
      study of multi-ethnic communities in Karachi and the 1990-91 Pakistan Demographic
      & Health Survey (PDHS). The results show that, although female age at first
      marriage has been gradually rising in both study samples, women in consanguineous
      unions married at younger ages and were less likely to use modern contraceptive
      methods. In the Karachi sample, women in first cousin unions experienced a higher
      mean number of pregnancies and also reported a higher mean number of children
      ever born (CEB). However, their mean number of surviving children did not differ
      from those born to women in non-consanguineous unions, implying higher prenatal
      and/or postnatal losses in couples related as first cousins. On the other hand,
      the PDHS showed both lower CEB values for women in consanguineous marriages and a
      lower number of surviving children. Given the continuing popularity of
      consanguineous marriage, these findings have important implications for future
      fertility reduction in Pakistan.

PMID- 10081243
TI  - [Clinical features, diagnosis and treatment of benign nonepithelial tumors of
      stomach].
AB  - The results of treatment of 24 patients with benign nonepithelial tumors of the
      stomach (BNTS) are presented. The majority of the tumors were leiomyomas (42%).
      The preoperative diagnostic algorithm included x-ray examination of upper
      gastrointestinal tract, endoscopic examination with histologic study (biopsy),
      ultrasound examination and CT. The best results were obtained in CT. The
      operation of choice in BNTS are wedge-resection of the stomach and enucleation
      (78.3% of patients).

PMID- 10081244
TI  - [Surgical treatment of postbulbar ulcers, complicated by penetration into
      pancreatic head].
AB  - The results of surgical treatment of 293 patients with postbulbar duodenal ulcers
      (PBU) have been analysed. It was established that PBU in the majority of cases
      are associated with several complications of the ulcer, the main of which being
      penetration of the ulcer into the pancreatic head. Comparing the results of
      resections of the stomach and organ-saving procedures in PBU, the author suggests
      that organ-saving methods in combination with vagotomy have some advantages over
      resectional methods.

PMID- 10081245
TI  - [Treatment of perforated gastroduodenal ulcers].
AB  - 139 patients with perforated ulcers of the stomach and the duodenum were
      operated. Diffuse peritonitis was encountered in 117 (84.3%) patients. Radical
      organ-saving operations were carried out in 111 (79.9%) patients. 6 patients
      (4.3%) died after operation. The authors suggest that usage of organ-saving
      operations in perforated pyloroduodenal ulcers complicated by peritonitis is
      quite justified and does not lead to increase in postoperative complications and
      mortality rate.

PMID- 10081246
TI  - [Laparoscopic horizontal gastroplasty].
AB  - The analysis of the first 14 operations of horizontal gastroplasty in patients
      with end-stage alimentary constitutional obesity was carried out, the operations
      being performed according to standard (9 patients) as well as laparoscopic method
      (5 patients). The mean body mass made up 133.6 kg, the mean height being 167.8
      cm. Patients age was from 22 to 42 years. All the patients operated by
      laparoscopic method were women. Technique of laparoscopic horizontal gastroplasty
      is described, indications and contraindications to the operation are established.
      It is demonstrated, that laparoscopic gastroplasty, as well as previously
      performed 530 horizontal gastroplasties with the help of fluoric-lausan goffer
      band, performed in clinic since 1984, in present time is one of the most
      perspective method of surgical correction of obesity. The application of this
      method results in substantial and steady decrease of body mass of the operated
      patients with minimal risk of complications during surgical procedure as well as
      in postoperative period.

PMID- 10081247
TI  - [Injuries and spontaneous ruptures of thoracic esophagus].
AB  - The results of treatment of 23 patients with injuries of thoracic part of the
      esophagus are analysed; in 10 cases spontaneous ruptures were detected. In 20
      patients suturing of the esophagus was carried out, as a rule wia transthoracic
      approach. Lavage-washing system in the area of injury was widely used.
      Insufficiency of esophageal sutures was detected in 35% of cases. Total
      postoperative lethality made up 26.0%, and in spontaneous rupture of the
      esophagus-50%.

PMID- 10081248
TI  - [Pancreatoduodenal resection with application of suturing device].
AB  - Operation of Whipple (pancreatoduodenal resection) is one of the most complicated
      in abdominal surgery; it is accompanied by great number of postoperative
      complications and lethal outcomes. The authors were the first in Russia to use
      suturing apparates by the firm USSC in pancreatoduodenal resection. The apparates
      were used in 8 patients, control group consisted of 10 patients previously
      operated conventionally with the use of uses UO series instruments. The
      application of the suturing devices made it possible to cut by half the duration
      of the operation, to secure painless postoperative course, to unify the operative
      procedure and makes it available for additional medical institutions.

PMID- 10081249
TI  - [Structural formation of adhesions in abdominal cavity and bowel walls in
      treatment of peritonitis by sorbent with absorbed metrinidazole or lipoorizinum
      (experimental study)].
AB  - Specimens of abdominal adhesions and bowels of rats were examined at light
      microscopy in treatment of diffuse purulent peritonitis (DPP) by kanamycin and
      artificial carbomineral sorbent SUMS-2p with metronidazolum or lipoorizinum
      adsorbed on the surface. Sorptional therapy of DPP was more effective in
      comparison with application of kanamycin (decrease in mortality rate of the
      animals were detected as well as the reduction in volume of the exudate and
      decline of inflammatory infiltration of the abdominal adhesions and bowels).
      However SUMS-2p with lipoorizinum showed to be active in treatment of DPP, than
      the sorbent with metronidazolum. This was confirmed by greater quantity of
      neutrophils, eosinophils and mast cells in the adhesions and by interintestinal
      abscesses formation.

PMID- 10081250
TI  - [Minimally invasive methods for treatment of cholelithiasis, complicated by
      choledocholithiasis].
AB  - Disease of the common bile duct (choledochal duct) was revealed in 18 from 531
      patients with bile tract lithiasis (3.4%), who underwent laparoscopic
      cholecystectomy and in 3 of 72 patients (5.4%), who underwent cholecystectomy
      through minilaparotomy approach. Stenosis of the large duodenal papilla was
      observed in 14 patients, choledocholithiasis in 9 patients. Endoscopic
      papillosphincterotomy (EPST) was performed in all cases. There were no
      complications. In 2 cases moderate amylasemia was detected. Laparoscopic
      cholecystectomy was performed 5 days after the procedure on the large duodenal
      papilla (5.1 days mean). Intervention with the use of mini-approach after EPST
      was carried out in patient with concrement of gall bladder duct stump, which was
      revealed 3 months after laparoscopic cholecystectomy. Mini-approach made it
      possible to perform reconstructive operations on bile ducts in combination with
      cholecystectomy in 3 patients. At present there are many tools which enable
      combined treatment of the bile tract lithiasis complicated by bile ducts
      pathology with low-invasive technique.

PMID- 10081251
TI  - [Improved method of dermatoplasty].
AB  - For restoration of dermal integument on hands, feet, major joints, face and neck
      in 104 patients special device was used which provided creation of split dermal
      flaps of new types--with fenestrated gaping perforations or entire flaps with
      areas of various thickness which enabled to preserve islands of full thickness
      skin at donor's sites or superficial dermal layers. The thickness of the
      transplants made up 0.4-0.6 mm in adults and 0.25-0.5 mm in children. Perforated
      flaps were transplanted in 128 cases, the flaps of variable thickness--in 31. 151
      operations (95.0%) resulted in complete recovering of the transplants, all wounds
      at donor's sites have closed spontaneously. Through 3-17 years after the
      operation the scars at perforations' sites looked hardly out of the ordinary, the
      areas of smaller thickness are unnoticeable, skin-grafts are soft and loading
      proofed. The decrease in complications' rate and improvement of functional and
      aesthetic results of treatment after the application of the device were stated.

PMID- 10081252
TI  - [Complications of indirect lymphotropic therapy in patients with suppurative
      wounds].
AB  - With the aim to reveal the frequency of complications in indirect lymphotropic
      therapy, retrospective analysis of 2136 case records of patients with festering
      wounds was carried out. In 1.59% of patients the following complications in the
      area of introduction of preparation were detected: protracted oedemas of hands
      and feet, severe painful syndrome, infiltration, necroses of soft tissues and the
      areas of atrophy and aseptic inflammation. Most commonly the complications arose
      in patients with peripheral circulation disturbances. The authors suggested this
      method of treatment to be contraindicated in peripheral blood flow disturbances
      and before its application the additional examination for revealing vascular
      disturbances is obligatory. In cases of painful syndrome, oedema, infiltration,
      hyperemia in the area of introduction of the drugs one day after the injection,
      indirect lymphotropic therapy should be discontinued.

PMID- 10081253
TI  - [Sutureless compression small intestine anastomoses creation using device with
      shape memory (experimental study)].
AB  - Specially developed device for creation of sutureless compression intestinal
      anastomoses was applied in 85 mongrel dogs. Function of the device is based on
      the effect of form memory of the alloy of Titanium nickelid, TH-10. The
      information about changes of mechanical strength (physical hermetism) of the
      anastomosis due to strength characteristics of the used construction as well as
      the study of blood supply in compression anastomosies in postoperative period is
      presented.

PMID- 10081254
TI  - [Chemoluminescence of blood and urine in diffuse appendicular peritonitis in
      children].
AB  - The results of the study of hemiluminescence of native blood, plasma and urine in
      56 children with diffuse purulent peritonitis demonstrate that changes of light
      sum of the luminescence of the investigated media could reflect aggravation of
      endogenous intoxication connected with development of organic insufficiency. The
      usage of blood and urine hemiluminescence for definition of the gravity of
      endogenous intoxication in diffuse forms of appendicular peritonitis in children
      is suggested.

PMID- 10081255
TI  - [Ultrasound assessment in diagnosis of uncomplicated inguinal hernia].
AB  - After the introduction of ultrasound (US) into general surgical practice one
      could hardly find more available and noninvasive technique for evaluation of
      groin pathology. We present an original US procedure elaborated for distinct
      visualization of soft tissues structures in patients with inguinal hernias. The
      inguinal region was examined preoperatively in 91 cases (US linear scanner with a
      7.5 MHz transducer frequency, "LOGIQ 700 MR", General Electric). The technique
      described in details was applied in 91 patients with proved or suspected disease
      of the groin during two year period. 82 cases had operative verification of the
      US diagnosis. In 2 cases inguinal hernias were clinically obvious but US test let
      false positive diagnosis to be avoided. Establishment of true diagnosis was
      possible in 4 patients with initial inguinal hernia only after US method was used
      as an additional aid. Ultrasound was found to be helpful in differentiation
      between processes vaginalis cyst (1 case), round ligament veins engorgement (1
      case) and inguinal hernia. As for hernia type the sonograms have predicted
      surgical findings correctly in 84.3% and 71.1% for indirect and direct inguinal
      hernias, respectively. Descriptive statistics of definite inguinal canal
      structures by US measurement are also included in the article. Sonography is a
      valuable modality in the preoperative examination of groin region in patients
      with inguinal hernia.

PMID- 10081256
TI  - [Choice of anesthesia in gunshot wounds of extremities].
AB  - The analysis of treatment of 452 victims with wounds of extremities for the
      period from 1984 to 1994 years was carried out. 171 patients had fire-arm wounds
      in local conflicts. Surgical wound management in 43% of victims was carried out
      under local infiltration anesthesia, in 28.3%--under conduction and prolonged
      conduction anesthesia, 27.8%--under general anesthesia and in 0.9%--under
      intraosseal anesthesia. The author suggests that as the gravity of firearm wound
      increases and wound infection progresses, the indications for infiltration and
      intraosseal anesthesia should be limited. In multiple and combined wounds,
      damages and tearing off the extremities, followed by shock, blood loss, general
      anesthesia would be indispensable. Conduction, prolonged anesthesia is quite
      reliable in mechanical cleansing of wound in process of surgical treatment, in
      early postoperative period, promotes improvement of regional hemodynamics and
      favours uneventful wound healing.

PMID- 10081257
TI  - [Neoplasm of colon, complicated by its partial obstruction in child].

PMID- 10081258
TI  - [Association of small intestine multiple diverticula with "kissing" ulcers].

PMID- 10081259
TI  - [Duodenal perforation, pericarditis and pneumothorax in newborn].

PMID- 10081260
TI  - [Laparoscopic cholecystectomy].

PMID- 10081261
TI  - [Salmonella aortitis in atherosclerotic aneurysm of aorta].

PMID- 10081262
TI  - [Isolated rupture of membranous part of trachea during closed chest trauma in
      child].

PMID- 10081263
TI  - [Angiofollicular lymphoid hyperplasia with ossification in abdominal surgery].

PMID- 10081264
TI  - [Mallison's tumor (glucagonoma)].

PMID- 10081265
TI  - [Pathogenetic substantiation of lung denervation in bronchial asthma and it's
      indications].

PMID- 10081266
TI  - [Period of professor V.I. Razumovskii's work in Saratov].

PMID- 10081267
TI  - [Potassium channels and the development of new drugs].
AB  - Ion channel modulation has recently become an attractive target for experimental
      and clinical research in a never-ending quest for drug development. Following the
      decades of domination of calcium channel blockers, currently the focus is on
      potassium channels and their modulators; this is one of the most rapidly
      developing fields of research. Because potassium channels have an important role
      in maintaining the membrane potential in all tissues and in shaping the action
      potential in the heart, potassium channel modulators are expected to provide
      better therapies primarily in cardiology (acute coronary syndromes, arrhythmias)
      but also in other branches of medicine.

PMID- 10081268
TI  - Possibilities of predicting results after surgical correction of ischemic mitral
      regurgitation on the basis of the degree of left ventricular dysfunction.
AB  - Results of surgical treatment for ischemic mitral regurgitation were
      retrospectively analyzed in 209 patients. All patients underwent myocardial
      revascularisation as well as mitral valve surgery. Preoperative myocardial
      infarction was registered in 75% of cases. These patients had different degrees
      of left ventricular dysfunction. Postoperative 30-day mortality was 4.3% for the
      whole group but higher in patients with lower ejection fraction. Looking at
      preoperative values of ejection fraction (EF), long term follow-up of 75 months,
      there is a statistically significant differences in survival rate (p < 0.05),
      freedom from cardiac decompensation (p < 0.05), and other complications (p <
      0.001), but only comparing two subgroups of patients, those with preoperatively
      ejection fraction lower and higher than 20%. Early postoperative, and especially
      long term results, are better in patients with higher ejection fraction.
      According to our experience, it is possible to predict the results after surgery
      for ischemic mitral regurgitation, depending on the degree of preoperative left
      ventricular dysfunction.

PMID- 10081269
TI  - [Population dynamics in Serbia--present status and problems at the end of the
      20th century].
AB  - INTRODUCTION: Population changes in Serbia in the last hundred years were very
      intensive in all fields of demographic development. They were positive, because
      the movement trend was basically up-to-date and as such responded to the needs
      and requirements of the problems in regard to population time. However, what was
      the intensity of these changes? What kinds of problems does Serbia face at the
      end of the 20th century? Methodology In order to establish precise data and
      isolate basic problems the following components were analyzed: fertility,
      mortality and population growth, age and ethnic distribution, migrations and
      spatial distribution. Data were taken from official vital statistics, censuses,
      censuses of people from the territory of former Yugoslavia, population
      projections and secondary analysis of relevant scientific findings. RESULTS:
      Serbia is faced with a number of problems in almost all segments of demographic
      development at the end of the 20th century. This primarily includes dual types of
      reproduction, open depopulation and fast population growth, reversible mortality
      trends of certain age-sex groups, a large number of refugees, pronounced
      emigration, especially of young and educated people, and greater or smaller
      distortions in the territorial distribution and in the development of certain
      subpopulations. DISCUSSION: Changes in population of Serbia have been intensive
      in all areas of demographic development giving it to a lesser or greater extent
      characteristics of contemporary population of developed countries. These changes,
      however, were either slow or began later, or too intensive and elemental, causing
      a series of distortions in the population development. CONCLUSION: The existence
      of demographic problems poses numerous questions. The basic one is to what extent
      do demographic distortions slow down the development of a country as a whole; how
      may the extreme differences in the population fertility levels represent a source
      of conflict, crises and instability, to questions concerning solutions and
      probabilities of strong political response. However, there is no dilemma that a
      population policy is necessary.

PMID- 10081270
TI  - [Clinical use of thrombopoietin (c-Mpl Ligand)].
AB  - INTRODUCTION: Results in clinical use of thrombopoietin have been published later
      than of other hematopoietic growth factors, because until recently the research
      was the least understood aspect of blood cell development. Reasons for this time
      gap were numerous, from inconvenient methods for measurement of thrombopoietin
      activity, to difficulties of its chemical purification. It is claimed recently
      that the understanding of platelet production has been profoundly advanced by the
      recombinant-gene synthesis and characterization of c-Mpl ligand (Megakaryocyte
      Growth and Development Factor), a substance which strongly enhances the
      proliferation of megakaryocytic line and the production of platelets. In this
      paper, some historical facts and biology of thrombopoietin are briefly discussed
      as well as the recent of the clinical use of thrombopoietin. THE HISTORY OF
      RESEARCH AND PRODUCTION OF THROMBOPOIETIN: The concept that the platelet
      production is underlying humoral regulation was first promoted by a group of
      Hungarian authors and they also named that humoral regulator--thrombopoietin.
      Further research followed in several countries including our own, and the initial
      studies proved that the serum of thrombocytopenic animals induced proliferation
      and maturation of megakaryocytic cell line and thrombocytosis in the peripheral
      blood of recipient animals. Later, when in vitro techniques were developed, it
      was shown that this humoral regulator has also a colony stimulating activity on
      megakaryocytic precursors. During the following two decades, studies of
      megakarycytopoiesis supported the hypothesis that two types of factors are
      involved in platelet production: early acting--megakaryocyte colony stimulating
      factors (Meg-CSF), and late acting--megakaryocyte potentiators, first of all
      thrombopoietin (TPO). However, extensive attempts on the purification of
      substances that either stimulate megakaryocyte development or augment platelet
      production failed to yield a homogeneous protein adequate for protein sequencing
      and cDNA cloning, the usual route which led to the production of other
      hematopoietic growth factors. Furthermore, a large number of other cytokines were
      described that possessed activity in various assays of megakaryocyte development.
      In spite of great number of accumulated data, it seemed in early 1990s that the
      production of a distinct, clinically useful lineage specific thrombopoietin will
      not be soon possible to achieve. The breakthrough occurred in 1994, when four
      groups of investigators published simultaneously their successful results on
      production of c-Mpl ligand, a substance which specifically binds to the Mpl
      receptors on megakaryocytes and has a very potent thrombocytopoietic effect. This
      production is based on genetic engineering and two companies (Kirin and Amgen)
      are already able to produce recombinant human thrombopoietin in large amounts,
      for clinical use. Although this substance is not commercially available yet, it
      passed the preclinical and clinical trials whose results are presented here.
      RESULTS OF THE PRECLINICAL TRIALS OF RECOMBINANT THROMBOPOIETIN: The chemical
      structure of human recombinant thrombopoietin (rTPO) is well defined, it is a
      glycoprotein consisting of 353 amino acids and molecular weight of 30 kD. The
      biologic actions of this molecule are in vitro: stimulation of megakaryocyte
      colony forming, endoreduplication of chromosomes and megakaryocyte maturation,
      and in vivo: increase of the number of progenitors and of megakaryocytes in the
      bone marrow, and an extensive elevation of platelet count in the peripheral blood
      4-7 days after its application. Also, in synergism with other pluripotent
      cytokines, it can stimulate the proliferation of other progenitors including
      CD34+ stem cells. Based on these data it is considered that c-Mpl ligand is the
      main physiological humoral regulator of thrombocytopoiesis, having the biological
      actions both of MegCSF and TPO.

PMID- 10081271
TI  - [Sedation and analgesia in intensive therapy].
AB  - INTRODUCTION: In the operating room, anaesthetist must provide unconsciousness,
      analgesia and muscular relaxation. In intensive therapy (IT), the rules are
      different and not every patient requires sedation, but almost every patient needs
      analgesia. The patient who is alert, calm and comfortable despite the presence of
      tubes and cannulas in the nose, mouth, radial artery, central vein, urethra,
      surgical wounds, pleural space etc. does not need any sedation. However, sedation
      and analgesia are clinically inseparable. If mechanical ventilation is not well
      controlled, muscular relaxants must be prescribed. There are a lot of trials in
      formulating an ideal sedative/analgesic regimen for each individual patient. THE
      RISKS OF SEDATION AND ANALGESICS: It is not rare that IT patients are oversedated
      or undersedated. Undersedation is followed by anxiety, pain, hypertension,
      tachycardia. The most important effect of oversedation is respiratory depression,
      hypotension, bradycardia, CNS depression, renal dysfunction, immunological
      depression. SEDATIVES AND HYPNOTICS: Benzodiazepines are among the most widely
      used drugs in IT. They have sedative, hypnotic, anxyolytic, amnestic,
      anticonvulsant and myorelaxant effects. Prolonged continuous infusion of
      benzodiazepines ought to be escaped because of prolonged sedation, accumulation
      and presence of pharmacologically active metabolites. They have proved to be
      safe, although they can depress ventilation. Since benzodiazepines are not
      analgesics, the combined use of an opioid and benzodiazepines is necessary. Many
      different benzodiazepines are available, but the agents most commonly used in
      critically ill are: midazolam, diazepam and lorazepam. Midazolam is the most
      extensively used. PSYCHOTROPIC DRUGS: The most frequently used drugs in the group
      of the butyrophenones are droperidol and haloperidol. Although these drugs are
      chemically unrelated to the phenothiazines they have similar actions. ANALGESICS:
      Opioids have the main place in management of analgesia in IT, especially in
      patients on mechanical ventilation. In management of postoperative analgesia,
      epidural route has advantage because less drug is necessary and cardiovascular
      and respiratory effects are minimal. Morphine is a standard opioid to which all
      others are compared. Intravenous bolus dose is 1-5 mg (0.1-0.15 mg/kg) or
      continuous infusion 2-15 mg/h. Hypotensive effect is caused by direct
      vasodilation and relief of histamine. Morphine has long elimination half-time and
      there is a danger of acummulation after prolonged administration. Morphine
      metabolites are pharmacologically active and renally eliminated. Prolonged i.v.
      infusion needs careful titration because of tolerance. Pethidine is less potent
      than morphine, usually given as a bolus dose (10 mg) or a continuous i.v.
      infusion (10-20 mg/h). Other opioid agents used in IT are: fentanil, alfentanil,
      sufentanil. Non-steroidal anti-inflammatory drugs (NSAID-s) are: aspirin,
      ibuprofen, ketoprofen, diclofenac, ketorolac. NSAID-s may have an opioid sparing
      effect and be of particular benefit for the relief of pain from bones and joints.
      They interfere with the metabolism at the site of the sensory nerve terminals.
      Several chemicals are released locally in response to tissue injury. Arachidonic
      acid is produced from damaged cell membranes. One series reactions is mediated by
      the enzyme cyclo-oxygenase (COX) and results in the formation of prostaglandins,
      prostacyclins and thromboxane. The cyclo-oxygenase pathway is inhibited by NSAID
      s. These analgesics, besides peripherally, also work centrally by mechanisms
      which are not in connection with COX inhibition. INTRAVENOUS AND INHALED
      ANAESTHETIC AGENTS: There are two barbiturates in use: thiopentone and
      pentobarbital. Although the main effect is hypnosis, the most important is
      anticonvulsant effect. Thiopentone is an agent for cerebral protection.
      Barbiturates have not achieved popularity in IT because of prolonged elimination
      and slow recov

PMID- 10081272
TI  - [Spiral computer tomography in the diagnosis of intracranial aneurysms].
AB  - In the last few years a significant advancement in radiological diagnostics has
      been made by the development of spiral computed tomographic technology. This
      technology, in comparison to conventional one, enables approach to isotropic
      imaging. In isotropic imaging spatial resolution is equal in all directions so it
      is the best possible way for getting the tridimensional images. These
      tridimensional images obtained by spiral computed tomography are of great
      importance for evaluation of anatomical details. Beside great speed and
      noninvasiveness, spiral scanner has capabilities for computed tomographic
      angiography. It means that spiral scanner depicts intracranial aneurysms with
      exceptional precision. This fact is of great value because the computed
      tomographic angiography, in some cases, can substitute completely the
      conventional angiography, which is an invasive method bearing risk. The
      sensitivity of computed tomographic angiography is around 88-96%--identical to
      magnetic resonance angiography. It is slightly higher or equal to conventional
      angiography, when intracranial aneurysms are concerned. Due to this reason the
      matter of algorithm of examination is imposed.

PMID- 10081273
TI  - [Pregnancy, delivery and acid-base status in twin pregnancy].
AB  - INTRODUCTION: Twin pregnancy may be a burden both during pregnancy and delivery,
      thus it is necessary, apart from special supervision and determination of Apgar
      scores, to perform testing of fetal blood. The purpose of this investigation was
      to determine the incidence of twin pregnancies during the three-year period,
      associated pathologies during pregnancy and delivery, as well as acid-base status
      of the twins. METHODS: The investigation included a group of women with twin
      pregnancy who underwent either vaginal or cesarean delivery during the three-year
      period (1994-1996) with special attention paid to acid-base status. RESULTS:
      During 1994, there were 80 pairs of twins (1.31%) delivered at the Department of
      Obstetrics and Gynecology in Novi Sad, in 1995--81 twins (1.22%) and in 1996,
      there were 70 pairs of twins (1.15%). The following associated pathologies have
      been recorded: PIH--7.98%, incompetent cervices--6.75%, cystitis--6.52%,
      pyelonephritis--0.61%. In 1994 term delivery was recorded in 60.71%, whereas
      preterm in 39.29%. In 1995 there were 61.67% term and 38.33% preterm deliveries
      and in 1996, there were 57.45% term and 42.55% preterm deliveries. Apgar score
      values were estimated at 1 and 5 minute and pH levels estimated for both twins as
      well as the values of PaCO2 (kPa), BE (mEq/l), BB (mEq/l), HCO3 (mEq/l), PaO2
      (kPa). Satyr. O2 (%)-acid-base status. CONCLUSION: Twin pregnancy being a high
      risk pregnancy, requires intensive monitoring: of the course of pregnancy and
      labor, proper choice of completion of the delivery, particularly in cases of
      preterm labor in order to avoid hypoxia, trauma and metabolic disorders and
      consequent damage of organs and systems.

PMID- 10081274
TI  - [Electrocardiography and echocardiography in the diagnosis of chronic cor
      pulmonale].
AB  - The study was aimed at evaluating the possibilities of electrocardiography (ECG)
      and echocardiography in establishing the diagnosis of chronic pulmonary heart
      disease (CPHD). Sixty patients with a chronic obstructive pulmonary disease
      (COPD) and clinical symptoms of cardiac decompensation were observed. The
      examined patients ranged from 26 to 74 years of age, the mean age being 59.25
      years. The diagnosis of CPHD was established by electrocardiography in 43
      patients (78.18%) while in 57 patients (95%) it was done by ultrasound
      cardiography. Morphologic changes of the right ventricle (RV) were quantified,
      i.e. the diagnosis of chronic pulmonary heart disease was confirmed by
      echocardiography parameters such as right ventricle free wall thickness--RVFWT
      (0.82 +/- 0.09 cm), enddiastolic right ventricle dimension--ERVD (3.78 +/- 0.73
      cm) and tricuspid regurgitation--TR (2.9 +/- 0.59, i.e. 2.58 +/- 0.55 after
      therapy). The information on the right ventricle function was provided by the
      values of echocardiography parameters, right ventricle ejection fraction--RVEF
      (30.98 +/- 5.88%, i.e. 34.1 +/- 5.64 after therapy) and right ventricle systolic
      pressure--RVSP (60.41 +/- 16.98 mmHG, i.e. 51.50 +/- 12.76 after therapy).
      Monitoring of these values after therapy, as well as of the RTO changes gave a
      good insight into the therapy effects. Echocardiography has been concluded to be
      of better sensitivity than ECG in diagnosing CPHD and both methods, noninvasive
      and easily applicable, have an important role in examining cardiac changes in
      patients with COPD.

PMID- 10081275
TI  - [Levels of "waste" halothane in operating rooms at gynecologic and obstetrical
      clinics--preliminary results].
AB  - INTRODUCTION: Medical staff working in surgical wards of hospitals, people that
      work on transport or storaging of gases and liquids, employees working on gas
      tanks and gas installations, mechanics for anesthetic devices and employees in
      the process of production of these substances are professionally exposed to
      anesthetic gases or and fumes that are released in their working environment. It
      has been confirmed that there were some deviations of indicators of the liver
      function after a long term exposure of the medical staff (surgeons,
      anesthesiologists, instrument nurses and anesthetists) to halothane and it has
      been notified that the level of wasted-halothane in the indoor air of the
      surgical theaters should be measured in order to get a correct and complete
      evaluation of the professional risk. The term "wasted-halothane" in this research
      means fumes of halothane that leave a closed circle: anesthetic device-
      respiratory organs (patient)--indoor air of the workplace (operating room).
      MATERIALS AND METHODS: Tests were done in the theaters of the surgical wards of
      the Department of Gynecology and Obstetrics of Novi Sad. During the testing
      period no ventilation system was used in any of the theaters. Tested groups
      included anesthesiologists, instrument nurses and anesthetists who were the
      members of the surgical team. Tests have not been done on same individuals, but
      the same workplace. Samples were taken using the "individual sample" method from
      the breathing zone of the tested person using a rubber pipe fixed on the
      shoulder. Pumps (personal samplers--"Casella") were set to absorb 0.2 liters of
      air per minute. Laboratory analyses of these samples were done using a method of
      desorption of the halothane fumes from the active coal with benzyl-alcohol, and
      their evaluation on gaschromatograph (Electron-Capture-Detector). The threshold
      Limit Value (TLV) of halothane fumes at the workplace is 40 mg/m3. RESULTS:
      During three days of sampling 32 samples of indoor air were taken from the
      surgical wards of the Department. 30 samples were taken in the surgical theaters,
      one in the hall between surgical theaters, and one in the room for rest of the
      staff. Concentration of halothane fumes in the theatre No 1 was between 6.9 mg/m3
      and 27.31 mg/m3 in anesthetists, between 33.08 mg/m3 and 37.62 mg/m3 in
      anesthesiologists and between 6.9 mg/m3 and 27.31 mg/m3 in instrument nurses. At
      the theatre No 2 concentration of halothane fumes was between 31.27 mg/m3 and
      37.9 mg/m3 in anesthetists, between 3.56 mg/m3 and 91.7 mg/m3 in
      anesthesiologists and up to 95.5 mg/m3 in instrumenting nurses. Concentration of
      halothane fumes in the theatre No 3 were between 4.19 mg/m3 and 17.18 mg/m3 in
      anesthetics, between 6.23 mg/m3 and 37.62 mg/m3 in anesthesiologists and between
      8.27 mg/m3 and 12.33 mg/m3 in instrument nurses. In the hall between these
      surgical theaters the concentration was 3.02 mg/m3 and 0.28 mg/m3 in the room for
      rest. DISCUSSION: Halothane fumes were present in the atmosphere of the working
      environment in significant quantities at all tested places Especially indicative
      were the results that showed that the concentration of halothane fumes in the
      theatre No 1, at the end of surgical operational program, was much higher than at
      the beginning, and what is even more important it was much higher than those in
      TLV in anesthesiologists and instrument nurses (more than twice higher). The
      differences of concentrations between specific occupations within the surgical
      team were also significant. Our results show that the most exposed were
      anesthesiologists and instrument nurses, who spent most time nearby the operation
      table. The anesthetists were much less exposed, due to the fact that they are
      assistants that often leave the surgical theater during the surgical
      interventions. Indicators illustrate that the increase of the concentration of
      halothane fumes depends on the length the surgical theaters were used. It shows
      an increase of halothane fumes co

PMID- 10081276
TI  - When to operate nonreducible ovary?
AB  - During the period from 1992, to 1996, ninety three girls with incarcerated
      inguinal hernias, mean age 6 weeks, underwent operation at the Clinic for
      Paediatric Surgery in Novi Sad. All infant girls had incarcerated ovaries or
      ovaries and fallopian tubes inside hernia sacs. The nonreducible ovaries were
      present at the time of operation in 35 (37%) girls and in 5 the ovary and tube
      were twisted. The ovary and tube, were twisted and ischemic at the time of
      operation, requiring oophorectomy in 2 out of 5 girls. The results of this review
      and recent experiences reveal that nonreducible ovary is not at risk of
      compression of its blood supply, but at significant risk of torsion. That is why
      asymptomatic nonreducible ovary should be treated as every incarcerated hernia-
      with urgent reduction, manual or operative.

PMID- 10081277
TI  - [Health aspects of population policies].
AB  - In developing countries family planning programmes are the main instrument of the
      populational policy and an important element of social influence in the domain of
      the population fertility policy in developed countries. The National Family
      Planning Programme in the Republic of Serbia was accepted by the Government and
      established in February, 1998. It is directed towards the improvement of
      reproductive health through promotion of family planning. The main objectives of
      the programme are: reduction of maternal, perinatal, neonatal and infants
      mortality, decrease of the number of unwanted pregnancies and abortions,
      promotion of contraceptive usage, efforts in prevention of sexually transmitted
      diseases, and meeting the needs of adolescents in relation to sexuality and
      reproduction. The first phase of realization of the Programme involves effective
      educative seminars for the primary health care workers--physicians of various
      specialties which are professionally engaged in family planning. Results of this
      Programme should provide improvement of reproductive health, as well as positive
      effects on demographic trends in Serbia in future.

PMID- 10081278
TI  - [Adult laryngeal hemangioma].
AB  - CASE DESCRIPTION: A patient aged 31 was admitted to the Ward because of
      hoarseness and difficulties in breathing. Family case history was negative.
      Personal case history shows pneumonia and jaundice. Hoarseness occurred suddenly,
      four months earlier, and did not change until hospitalization. The patient
      occasionally woke up for air loss. He first came for otolaryngological
      examination on November 23, 1995, and was admitted for examination and treatment.
      By frontal rhinoscopy, oropharingoscopic and otoscopic findings are regular.
      Indirect laryngoscopy shows regular findings in the hypopharynx. The epiglottis
      has regular configuration and appropriate insertion, but lay extremely low,
      covering the passage to larynx and thus making its examination impossible. As it
      was impossible to examine the patient by indirect laryngoscopy, we decided for
      directoscopy of larynx in neurolept analgesia, finding that the mucous membrane
      of epiglottis and larynx was pink, smooth, and glossy. The passage to larynx was
      free. Plicae aryepiglotticae and false vocal chords were regular. Morgagni's
      ventricles were free. The left vocal chord was yellowish, with smooth surface,
      sharp edge, slightly edematous. The front third of the upper surface of the right
      vocal chord showed a wide grip of a large globular formation of livid colour, the
      size of a cherry, taking two thirds of larynx's lumen, and a hematoma on the same
      vocal chord, spreading into Morgagni's chamber. Due to the local findings the
      patient was intubated and given general endotracheal anesthesia. In direct
      laryngomicroscopy, ablation of the polypous formation was performed. Bleeding was
      minimal. The removed material was sent for histopathological analysis. The post
      operative course passed regularly. The patient was released from hospital on the
      third postoperative day without subjective discomforts and with appropriate local
      post-operative findings. Histopathological finding: hemangioma cavernosum. At
      control examinations the patient shows no subjective discomforts and has regular
      local findings, with no signs of local recurrence. DISCUSSION: The first larynx
      hemangioma was described by Mackenzie in 1871 (1). In 1921 Sweeter (1) classified
      hemangiomas as infantile and adult. Infantile hemangiomas are in 40-50% cases
      followed by multiple skin and gastrointestinal localizations (2). They are more
      frequent with girls. Dyspenia and inspiratory stridor with obstruction signs and
      cough are the main symptoms with neonates (3,4,5,6,7). These discomforts are not
      permanent, there are periods of improvement and deterioration. In most cases a
      spontaneous involution of hemangioma occurs during the second year of life. Adult
      hemangiomas are bluish red, clearly defined, appearing most often in the region
      of glottis and supraglottis. They are more frequent with males. The principal
      symptom is hoarseness, occasional hemoptysis, and in advanced cases dysphagia and
      difficult breathing (1,8,9). They do not show tendency of spontaneous regression.
      The sources give varied opinions on therapeutic procedure with laryngeal
      hemangioma (3,5,7,10,11,12,13,14). The factors influencing the choice of therapy
      are age, type, size and localisation of the tumor, and the patient's discomforts.
      With infantile hemangiomas which do not cause significant discomforts, we can
      expect spontaneous regression (15,16,17). The greatest discomforts are caused by
      hemangiomas during the first years of life, when followed by difficult breathing
      and choking. In these cases tracheotomy is inevitable. Radiotherapy used to play
      the principal role in therapy of hemangiomas (15,10,12). Nowadays the treatment
      of laryngeal hemangiomas with neonates is done with steroids (3,5,7),
      embolisation (5,14), laser (3,713) and cryotherapy (12). Adult hemangiomas are
      mostly treated surgically, applying various methods, from tumor ablation to
      laryngectomy, depending on the size of tumor (1,8,18,19,20). (ABSTRACT TRUNCATED)

PMID- 10081279
TI  - [Leishmaniasis: case report].
AB  - INTRODUCTION: Leishmaniasis is a chronic parasitic disease of the
      reticuloendothelial system which is manifested by gradual onset, unspecific
      disorders and can take a form of visceral, cutaneous or mucocutaneous
      leishmaniasis. The aim of the study is to present the patient who was treated for
      visceral leishmaniasis at the Clinic for Infectious Diseases in Novi Sad. CASE
      REPORT: A patient, 22 years old, had been admitted at the Clinic one month after
      the beginning of the disease with gradual onset malaise, fatigue, loss of
      appetite, intermittent temperature and night sweating. A few days before the
      admittance to the hospital, dark colour of urine and the pain under the left rib
      occurred. On admission, the patient had been afebrile, dehydrated, intoxicated,
      he had subicteric sclerae with enlarged liver and extremely enlarged spleen.
      Laboratory findings revealed anemia, leucopenia, and increased level of gamma
      globulins. Hypercellularity of the bone marrow with cells of all degrees of
      maturity had been determined by sternal puncture. We have epidemiologically
      obtained information about the bites of a mosquito from the Phlebotomus genus at
      the Adriatic coastal region, two years and two months ago. The diagnosis had been
      confirmed by the formol-gel test and by the indirect hemaglutination test.
      Leishmaniae donovani had been found in the bone marrow punctate. TREATMENT: The
      patient had been treated by appropriate doses of N-methyl-glucamine-antimonate
      (Glucantime), during three weeks, after which he was cured. During the one-year
      follow-up period normalization of laboratory findings as well as liver and spleen
      ultrasonographic findings occurred. CONCLUSION: Because of gradual onset and
      polymorphic troubles during the beginning of leishmaniasis, many diseases can be
      taken into account for diagnostic differentiation. From this study it is obvious
      that even the possibility of such a disease must be considered, despite the fact
      that it is rare in our region, because fatal outcome is avoidable only by the
      timely diagnosis and therapy.

PMID- 10081280
TI  - [Use of photoprotective measures in relation to actual exposure to solar rays].
AB  - OBJECTIVE: There is evidence that in spite of worldwide campaigns against
      excessive sun exposure, children as well as adults still spend long periods in
      the sun. The purpose of this study was to evaluate sun exposure in a group of
      doctors of different specialties and to compare their knowledge about sun
      protection methods with regular use of sun protection products. METHODS: 51
      doctors of different specialties, volunteers, mean age 40.78, filled out
      questionnaires with 21 multiple choice questions about their skin type, sun
      exposure habits, sun protection habits and questions about meaning of the Sun
      Protection Factor. RESULTS: Thirty-three percent of our study participants spent
      more than two peak ultraviolet hours outdoors every day, and additional 33.33%
      are sun exposed for longer than 5 hours, regularly. Only 39% of them utilized
      sunscreens. Majority of sunscreen users utilized less than 100 ml of commercial
      sunscreen products which is an inadequate amount for full body protection per
      year. Majority of study participants did not believe that sunscreens could
      prevent skin cancer, but 57% of them believed that these compounds can slow the
      process of skin aging. Meaning of the term Sun Protection Factor is not familiar
      to 84.3% study participants. The two most common reasons for not using sunscreens
      are time consuming application and high cost. CONCLUSION: Results of the
      presented study confirm our statement that there is bad understanding of a need
      for sun protection which is in correlation with deficient application of sun
      protective measures. It should be stressed out that our study participants lack
      well formed sun protection habits.

PMID- 10081281
TI  - [Hospitals in Europe and Yugoslavia through the centuries].
AB  - The primary object of this paper is to give a retrospective of hospital
      development in Europe and Yugoslavia for the past twenty-five centuries. The
      earliest records of hospitals called the "iatreia" date back to the V century
      B.C., ancient Greece. The sick in those hospitals were treated with drugs as well
      operated on. The Romans, during the reign of the emperor Augustus, built
      valetudinaries within military camps. The name "hospital" was introduced in the
      IV century A.D. and has been used ever since. The first hospital was founded in
      Cesarea, i.e. in the East Roman Empire in Asia Minor. The chronology of the
      hospital development in the Middle Ages is given in table 1--"Chronology of
      Hospital Development in the Middle Ages." St. Sava (Nemanjic) founded the first
      Serbian hospital in the Monastery of Hilandar about 1199 and in 1208/1209 a
      hospital in the Monastery of Studenica. In the hospital of the Monastery of St.
      Arhangel in Prizren, according to the regulations prescribed by tzar Dusan, only
      curable patients were to be treated. The first hospital in Vojvodina in Bac near
      Novi Sad dates back to 1234. More data about hospitals in former Yugoslavia are
      given in table 2--"The Oldest Hospitals in former Yugoslavia" and about the
      Frontier Hospitals in Vojvodina in table 3--"Frontier Hospitals for the Wounded
      and Sick in Vojvodina". The first medical high school was established in Salerno
      in the IX century and the first European University in Bologna in 1088, where the
      School of Medicine was founded in 1156. The University in Paris was founded in
      1107 and in Oxford in 1145.

PMID- 10081282
TI  - [Measurements and indices of the central part of the lateral cerebral
      ventricles].
AB  - INTRODUCTION: Halls of the lateral cerebral ventricles' central parts are mainly
      formed of caudate nucleus. Increase of cerebral ventricular system volume, called
      central atrophy, is a result of decrease in basal ganglia volume. In this paper,
      lateral cerebral ventricles' central parts measures were determined and indexes
      were calculated, as well as the correlation between these parameters and the age
      of examinees. Presence of sexual dimorphism was investigated, too. MATERIAL AND
      METHODS: Lateral cerebral ventricles' central parts measures and indexes were
      determined in 60 healthy volunteers (30 males and 30 females), aged from 15 to 60
      years (x = 39.47 +/- 12, 18 years), without positive neurological and MRI
      findings. The shortest and the longest distance between walls of the cerebral
      ventricles' central parts and the maximal width of the brain and skull at the
      same levels were determined, and according to the obtained data, proper indexes
      were calculated. Sexual dimorphism of the maximal width of the brain and skull at
      the level of both the shortest and the longest distance between walls of the
      cerebral ventricles' central parts was shown. RESULTS: Significant, positive
      correlation was obtained between age and linear measures determined at the level
      of both the shortest and the longest distance between walls of the cerebral
      ventricles' central parts, as well as indexes calculated at the basis of the
      aforementioned data. This positive correlation has the highest level of
      statistical significance at the level of the shortest distance between walls of
      the cerebral ventricles' central parts. CONCLUSION: Widening of the lateral
      cerebral ventricles' central parts, especially at the frontal part, could be
      explained as a sign of the caudate nuclei volume decrease, i.e. the central
      atrophy. This is in positive correlation with age.

PMID- 10081283
TI  - [Methodological quality of studies and publications].

PMID- 10081284
TI  - [Methodological quality of controlled studies in the "Medizinische Klinik"
      journal. Analysis of contributions appearing between 1979 and 1996].
AB  - BACKGROUND: Standards concerning design, performance and analysis of controlled
      clinical trials have improved during the last decades. A number of
      recommendations has been published. Their impact is hardly known. METHODS: Using
      a standardized procedure controlled clinical trials published between 1979 and
      1996 in the "Medizinische Klinik" were identified and reviewed for their quality
      of design, analysis and presentation of results. Results were subdivided by 6
      three-year-periods. RESULTS: 132 trial reports were identified. Randomisation was
      reported in 107 papers (81%) with further details of the procedure in only 20.
      Adequate concealment is recognizable in 21 papers. Results of baseline
      comparisons were presented in 52 publications (39%). 57 reports did not mention
      any blinding although no arguments are given. Information about drop-outs can be
      found in 90 publications. In most papers, however, drop-outs were omitted from
      the analyses. An adequate intention-to-treat analysis is provided in 7 reports.
      Due to missing or incomplete data many results and statistical tests can not be
      recalculated by the reader. Only 6 papers presented some kind of power
      calculation. Methodological quality has improved over the complete time period
      with a certain weakening in the three years before 1996. CONCLUSION: Quality
      criteria for a meaningful controlled clinical trial are not sufficiently met in a
      number of cases. Percentages are in accordance with the international literature.
      Major problems comprise sample size calculation and the application of the
      intention-to-treat principle.

PMID- 10081285
TI  - [Cardiopulmonary parameters in hyperthyroidism].
AB  - BACKGROUND: Hyperthyroid patients often suffer from impaired exercise capacity
      with dyspnoea. Two well established, non-invasive methods were used to evaluate
      the influence of hyperthyroidism on cardiopulmonary function. PATIENTS AND
      METHODS: In 42 patients with hyperthyroidism we performed spirometry and
      cardiopulmonary exercise testing before and after 7 days of propranolol therapy
      as well as in euthyroidism. RESULTS: In hyperthyroidism reduced vital capacity
      and 1-second capacity were observed (95.5 +/- 2.4% vs 102.6 +/- 1.5%; p = 0.0087;
      89.4 +/- 2.3% vs 95.2 +/- 2.2%; p = 0.0179). No changes showed during beta
      blockade. At the anaerobic threshold reduced tidal volume and enhanced
      respiratory frequency were noted (1119.8 +/- 48.9 ml vs 1289.3 +/- 62.7 ml; p =
      0.0227; 28.3 +/- 0.8 vs 25.4 +/- 0.9; p = 0.0012). A significant tachycardia
      could be shown. Impaired response to exercise in pulse and respiratory frequency
      were observed. Work at the anaerobic threshold was impaired in hyperthyroidism
      (70 +/- 5 watts vs 86.9 +/- 5.7 watts; p = 0.016) and did not change during
      propranolol therapy. Oxygen pulse at the anaeorbic threshold was reduced in
      hyperthyroidism (7.7 +/- 0.4 ml O2/beat vs 9.1 +/- 0.4 ml O2/beat; p = 0.0012)
      and increased with propranolol (8.9 +/- 0.4 ml O2/beat; p = 0.0001). CONCLUSION:
      In hyperthyroidism significant changes in cardiopulmonary function were noted at
      rest and exercise. High resting function and impaired response to exercise
      suggest a cardiopulmonary work with low efficiency. Propranolol leads to
      economization and lowers patients complaints.

PMID- 10081286
TI  - [Cardiology update. I: Electrophysiology].

PMID- 10081287
TI  - [Non-enzymatic glycation and oxidative stress in chronic illnesses and diabetes
      mellitus].
AB  - New approaches in biochemistry and molecular biology have increased the knowledge
      on the pathophysiology of chronic diseases as late diabetic complications,
      Alzheimer's disease, arteriosclerosis and vascular disease by defining the
      concept of "AGE-formation and oxidative stress." Nonenzymatic glycation, in which
      reducing sugars are covalently bound to free aminogroups of macromolecules,
      results in the formation of Advanced Glycation End products (AGEs) which
      accumulate during aging and at accelerated rate during the course of diabetes.
      Glycation accompanying oxidation processes support AGE-formation. AGE-formation
      changes the physicochemical properties of proteins, lipids and nucleic acids. In
      addition, binding of AGEs to specific surface receptors induces cellular
      signalling and cell activation. Interaction of AGEs with one of the receptors,
      RAGE, generates intracellular oxidative stress, which results in activation of
      the transcription factor NF-kappa B and subsequent gene expression, which might
      be relevant in late diabetic complications. CONCLUSION: Knowledge of the basis
      molecular mechanisms allows to understand the interplay of different inducers
      such as redicals, cytokines, AGE-proteins and amyloid-beta-peptids and to define
      oxidative stress as a "common endpoint" of cell dysfunction. With respect to
      therapeutic options it is now possible not only to optimize blood glycemic
      control, but also to design drugs such as AGE-inhibitors and AGE-"cross-link"
      breakers. In addition patients with chronic disease associated with increased
      oxidative stress ay benefit from an antioxidant rich (and AGE protein poor?)
      nutrition.

PMID- 10081288
TI  - [Acute hantavirus infection caused by a genetically newly identified viral
      strain. Severe and complicated course of hemorrhagic fever with renal syndrome
      (nephropathia epidemica)].
AB  - HISTORY AND CLINICAL FINDINGS: A 49-year-old patient, a hobby hunter, fell ill
      acutely with joint and limb pain, abdominal pain, nausea and subfebrile
      temperatures. At hospitalization, the patient was in bad general condition,
      showing ascites and lid edema, and acute renal failure was diagnosed.
      INVESTIGATIONS: Laboratory tests revealed marked thrombocytopenia (15,000/ml),
      leucocytosis, elevated levels of creatinine, blood urea nitrogen and liver
      enzymes, respectively. Blood gas analysis showed metabolic acidosis. Chest X-ray
      showed an interstitial fluid accumulation, abdominal ultrasound disclosed ascites
      and enlarged kidneys as in acute renal failure. Immunologic tests verified the
      diagnosis of an acute hantavirus infection, by use of specific molecular biology
      techniques a previously unknown virus strain was identified. TREATMENT AND
      COURSE: Hantavirus infections in western Europe usually show a benign course.
      However, in the present case, acute progressive pulmonary failure developed
      despite effective dialysis so that mechanical ventilation was necessary for
      several weeks. Dialysis had to be carried out for 17 days. As a complication a
      severe ulcero-destructive tracheobronchitis developed, caused by Aspergillus
      fumigatus. After several weeks, both renal and pulmonary function had returned to
      normal. CONCLUSION: Hantavirus infections may lead to severe and complicated
      courses also in western Europe. By use of new immunologic and molecular biology
      techniques a specific diagnosis is possible.

PMID- 10081289
TI  - [Ciguatera poisoning. Growing differential diagnostic significance in the age of
      foreign tourism].
AB  - BACKGROUND: In the tropic sea there are carnivore fishes, e.g. the "peak bass",
      that incorporate toxin producing seaweed and can cause the ciguatera
      intoxication. Due to the frequent tourism to tropic regions even more cases of
      ciguatera intoxication can be seen in Europe. The late phase of ciguatera
      intoxication has hardly been recognized due to its different unspecific symptoms.
      In some cases ciguatera intoxication can even grow a vital threatening. CASE
      DESCRIPTION: Four patients from a travel group addressed us 4 and 14 days after
      breaking off their holidays in the Dominican republic. They presented complex
      neurological symptoms including paraesthesia, nervousness, inverse temperature
      perception, muscle cramps, headache and dizziness. The physical and apparative
      investigation of the patients, whose age ranked between 22 and 31 years, was
      totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was
      the clue to the symptom causing dinner at their holiday location existing of
      "peak bass and lemon sauce". First symptoms in all members of the travel group
      were diarrhea, sickness and sweating. In this late phase only a symptomatic
      therapy could be offered. CONCLUSION: The here described cases show the
      importance of a comprehensive information for tropic travellers as for physicians
      accounted to in the acute phase of ciguatera intoxication, because recognized
      early enough (within the first 24 hours) the total symptomatology of ciguatera
      intoxication can be prevented effectively by intravenous infusions of mannitol.

PMID- 10081290
TI  - [Phthisis atra as silicosis complication].

PMID- 10081291
TI  - [12 basic rules in drug therapy of tumor pain].
AB  - Successful pharmacologic treatment of cancer pain is founded upon careful
      assessment and measurement of pain before and during therapy. Strong opioids
      should be used timely in accordance to the WHO 3-step analgesic ladder. The oral
      route should always be favored. Frequent opioid side effects include
      constipation, temporary nausea and vomiting and are to be treated adequately.
      Slow release morphine preparations are to be administered every 12 hours.
      Adjustment of dose follows pain intensity. Immediate release morphine for
      breakthrough pain should be provided routinely to patients maintained on a 12
      hourly regimen of slow release morphine. The appropriate rescue dose will be 1/6
      of the total daily morphine dosis. In case of changement of route of
      administration the relative potency ratio of oral morphine to parenteral morphine
      is about 3:1. The coadministration of nonopioids is essential for the relief of
      cancer pain in many cases. Adjuvant drugs may provide pain relief in specific
      types of pain (e.g. neuropathic pain).

PMID- 10081292
TI  - [Diverticulosis of the large intestine].

PMID- 10081293
TI  - [Responsibilities of ethics committees].
AB  - Increasing numbers of clinical research projects are submitted to ethical
      committees (institutional review boards) for approval. New therapeutic
      developments have to be evaluated by these committees to protect
      patients/volunteers. Thus, the responsibility of ethical committees is
      increasing. The "Nurnberger Kodex" and the "Declaration of Helsinki" are the
      background for these evaluations. According to the German drug law the physician
      is obligated by law to submit the protocol to such a committee. In addition,
      local state physician authorities require such a procedure. Important
      considerations during the review process besides ethical aspects are the informed
      consent, which should be written in an understandable form, and the obligations
      of the insurance.

PMID- 10081294
TI  - [Evaluation of the 104th Congress of the German Society of Internal Medicine
      1998].

PMID- 10081295
TI  - [Theories on psychotherapy in Germany].

PMID- 10081296
TI  - [Clinical hypnosis. Current status of theory and empirical aspects].
AB  - Hypnosis as a traditional healing method, in its more recent development, has
      generated a multitude of techniques. These serve as practical tools which can be
      combined with other therapy techniques for the treatment of medical,
      psychosomatic and neurotic disorders. Based on 80 group studies (to date) the
      empirical evidence for the effectiveness of hypnosis is considerable and proves
      its clinical impact in various areas of application. As a theoretical foundation
      a number of hypotheses have been formulated, which describe hypnosis as a complex
      phenomenon with biological, cognitive and social aspects.

PMID- 10081297
TI  - [Diagnosis and management of patients with psychogenic disorders in family
      practice. Results of a field study].
AB  - The majority of patients with psychological disorders are seen in primary care.
      The diagnosis of the general practitioner (GP) influences decisively the
      subsequent treatment. Our study provides an insight into GP's diagnosis and
      treatment. 18 GP's and a psychotherapist rated 572 patients using a global
      diagnostic rating scale and the impairment score (BSS). The GPs noted down their
      treatment. The patients filled in symptom checklists (SCL-90-R, GHQ-12).
      Agreement between the doctor and the researchers on mental ill health was modest.
      GPs identified 51.4% of the patients with psychological disorders. Adjustment
      disorders were often ignored by GPs. They prescribed psychotherapy for 3.3% of
      their patients, especially patients with somatoform disorders and with high
      values in the impairment score. A path analysis shows, that psychotherapists'
      ratings agree much more with patients' self-assessment than GP ratings.

PMID- 10081298
TI  - [Fear of death and willingness to consider organ donation among medical
      students].
AB  - The present study represents an attempt to examine the relationship of fear of
      death and willingness to consider organ donation. A group of 124 medical
      students, 72 entering and 52 graduating from university, aged 19-37 years,
      completed a fear of death and dying scale (FVTS of Ochsmann) and a questionnaire
      about behavioral and attitude variables concerning organ donation. There were no
      significant sex and age differences on the FVTS in the total sample. 1st-year
      medical students had higher scores for the fear of meeting death related to
      lacking experiences with dying friends or patients. Selected item analyses for
      focus groups of students, who were for or against organ donation, had
      reservations about donation or had signed an organ donor card, revealed only a
      few significant differences on the FVTS. Both students without donor card and
      with reservations about donation scored significantly higher for fear of physical
      destruction. Organ donor card holders, however, scored significantly lower and
      accepted autopsy and anatomic dissection of their corpses twice as frequently as
      the others. Possible implications of these findings for medical education and
      future research are addressed.

PMID- 10081299
TI  - [Psychological health, locus of control and personality of medical students of a
      traditional and an alternative study program].
AB  - Traditional medical curricula are widely criticised. Medical students show a
      higher prevalence of psychological distress. New problem-based curricula are said
      to promote higher satisfaction with medical schools and lower psychological
      distress. This goes together with achievement comparable to traditional
      curricula. A study with preclinical medical students in a traditional (Gottingen,
      n = 126) and an alternative (Witten/Herdecke, n = 25) medical curriculum was
      carried through, concerning subjective wellbeing (depression/anxiety), locus of
      control and primary personality traits. Students in the problem-oriented
      curriculum show lower prevalence of psychological distress and less experience of
      powerlessness and fatalism (external locus of control). There is no striking
      difference in the primary personality traits. Results are discussed with respect
      to long-term evaluation of future alternative curricula in Germany.

PMID- 10081300
TI  - [Clinical controlled studies, incontrovertible support of evidence-based
      medicine].

PMID- 10081301
TI  - [Clinical study of the month. The LIPID study: "long-term intervention with
      pravastatin in ischaemic disease"].
AB  - The LIPID study is a placebo-controlled, double-bind, randomized trial, performed
      in 9014 patients with coronary heart disease and total cholesterol levels of 155
      to 271 mg/dl. After a mean follow-up of 6.1 years, patients receiving pravastatin
      (40 mg/day) had significantly (p < 0.001) lower death rate from coronary heart
      disease (24%), lower overall mortality (22%) and lower incidence of all
      cardiovascular outcomes (20 to 29% depending on the event). Interestingly enough,
      the reduction in death from coronary heart disease or nonfatal myocardial
      infarction was observed whatever the initial cholesterol concentration, and
      already significant if total cholesterol was < 213 mg/dl and LDL cholesterol was
      < 135 mg/dl. Thus, in secondary prevention, the favourable effect of the statin
      on the coronary heart disease outcomes is observed even in case of initial
      cholesterol levels yet considered as "normal".

PMID- 10081302
TI  - [Image of the month. Hepatic hydatid cyst].

PMID- 10081303
TI  - [How I treat ... tachyarrhythmias with percutaneous radiofrequency ablation].
AB  - Radiofrequency ablation allows the curative treatment of supraventricular
      tachycardia and some types of ventricular tachycardia. We reviewed the technical
      modalities of radiofrequency for the different types of supraventricular
      tachycardia.

PMID- 10081304
TI  - [Clinical case of the month. Inaugural myocardial infarction from a congenital
      coronary-cardiac fistula].
AB  - We report a case of a 47-year-old woman with a typical clinical pain, a ST
      elevation in lateral EKG leads and an increase of the CPK-MB enzymes serum level
      suggesting the diagnosis of an acute lateral myocardial infarction. The emergency
      coronary arteriography did not showed any coronary artery lesions but a coronary
      artery fistula from the left main coronary artery to a terminal thrombosed
      aneurysmal dilatation located between the left atrium and the right pulmonary
      artery. Through this case report, authors will discuss aetiology,
      physiopathology, clinical presentation and treatment of coronary artery fistulae.

PMID- 10081305
TI  - [Hypercholesterolemia-related cardiovascular risk: a continuum from a notion of
      normality, intervention threshold and therapeutic objectives].
AB  - There appears to be a continuum between the cardiovascular risk and the level of
      blood cholesterol, which hinders the definition of normal values, intervention
      threshold and therapeutic goals. The more and more convincing evidences provided
      by the "Evidence-Based Medicine" should be confronted to the pharmaco-economical
      constraints in order to first focus the essential of the efforts and resources on
      the target population with the highest risk. Unfortunately, the therapeutic
      strategy concerns a rather high percentage of the population of industrialized
      countries.

PMID- 10081306
TI  - [Interventional catheterization in pediatric cardiology].
AB  - During the last decades there has been an enormous increase in the use of
      transcatheter techniques to improve or correct congenital heart lesions. Balloon
      valvuloplasty and angioplasty, closure of heart defects, foreign body retrieval
      and ablation of conduction bundles are now available to the pediatric
      cardiologist. The variety of lesions so treated continues to expand and equipment
      continues to improve. However therapeutic catheterization techniques should only
      replace conventional surgery as the initial procedure of choice in lesions for
      which the results of these interventions are either similar to or better than
      those reported for the alternative surgical treatment. The purpose of this paper
      is to present the current state-of-the-art of this exciting new discipline.

PMID- 10081307
TI  - [The physician faced with an iodine deficiency: individual management of a public
      health problem].
AB  - Urinary iodine was measured in samples collected during the first week of life in
      newborns from the areas of Liege in Belgium and Cluj in Romania. In Liege, severe
      iodine deficiency was seen in 1 out of 8 newborns and mild iodine deficiency in 1
      out of 3. A greater proportion of newborns showed iodine deficiency in Cluj.
      Since public health measures to prevent iodine deficiency have not been set up
      yet by belgian authorities, the practitioner has to ensure individually optimal
      iodine intake, particularly in pregnant women, in newborns and during infancy.

PMID- 10081308
TI  - [Halitosis: a multidisciplinary problem].
AB  - Bad breath, or halitosis, affects between 50 and 65% of the population. Despite
      its frequency, this problem is often unaccepted and declared taboo. In about 8%
      of the cases, bad breath is related to an ENT pathology (sinusitis, tonsillitis,
      ...). More rarely it is caused by a metabolic (diabetes, trimethylaminuremia,
      ...) or gastric dysfunction. Ninety percent of the cases however, are associated
      to an oral disease: either gingivitis due to an inadequate removal of dental
      plaque, especially from interdental spaces, or periodontitis (alveolar bone
      destruction), or bacterial accumulation on the dorsum of the tongue. In most
      cases, an intensive disinfection of the mouth by scaling and root planing and/or
      instruction of a perfect oral hygiene will be sufficient to solve the problem.
      Perfumed mouthwashes or toothpastes will only give a short-term masking effect.
      An effective collaboration between a dentist or a periodontist and an ENT
      specialist is of great importance to dealt with bad breath.

PMID- 10081309
TI  - [Hue and cry over pens?].
AB  - Pens are accused to be potential vectors for nosocomial infections. Their role
      cannot be denied. However, a poor compliance to hand washing is probably the real
      culprit. Such action should be more systematic between examining successive
      patients. However, one has to chose carefully the cleaning and antiseptic agent
      baring in mind the irritation potential of such product. Indeed, the repetitive
      minimal aggression of the stratum corneum may lead to a paradoxical increase in
      bacterial contamination. It is responsible for increased roughness of the skin
      and occurrence of subjective symptoms which abate the sufferer compliance.

PMID- 10081310
TI  - [Malignant tumors of unknown origin].
AB  - Cancers of unknown origin form a specific clinical entity. The diagnostic
      procedure has to be guided by the therapeutical possibilities and requires a
      biopsy. Immunohistology, electron microscopy and cytogenetics are informative for
      carcinomas and poorly differentiated adenocarcinomas. The clinical status and the
      histology allow the definition of groups of patients who can benefit from a
      specific therapy and have a better prognosis. For the other patients, the
      prognosis is severe and there is no efficient therapy available. Such tumors are
      usually characterized by a very aggressive behaviour.

PMID- 10081311
TI  - [Atheroembolism and cardiac surgery: importance of preoperative management].
AB  - OBJECTIVE: Atheroembolization is a recognized complication of cardiac surgical
      procedures, and has been implicated in postoperative stroke, renal failure,
      multiorgan failure, and death. Preoperative identification of patients at risk
      for developing atheroemboli is essential. The aim of this study was to determine
      preoperative risk factors for atheroemboli and to assess the postoperative course
      of the patients who developed atheroembolic syndrome. METHODS: A retrospective
      record review was conducted. From 1/1990 to 12/1994, 5.486 patients underwent
      coronary artery bypass grafting (CABG), valve operations, or other cardiac
      surgical procedures at the Massachusetts General Hospital. Among this population,
      107 patients (1.9%) developed atheroembolic syndrome. There were compared to a
      concurrent population of 925 patients operated during the same period. RESULTS:
      Patients who developed atheroemboli were older, with an increased incidence (p <
      0.01) of hypertension, cerebrovascular disease, and aortoiliac disease. Many had
      a complicated course after catheterization, with renal insufficiency (35%) and
      evidence of peripheral emboli (12%). Average Intensive Care Unit stay, hospital
      stay, and hospital cost of these patients were 16.8 days, 48.4 days and $88,000
      respectively, compared to 1.5 days, 9.6 days and $23,000 for the concurrent
      population. Of these 107 patients only two were discharged home, the others
      either died (48 patients, or 25% of all cardiac surgical deaths during this
      period), or went to rehabilitation or chronic hospital facilities. Twenty-seven
      autopsies were performed and invariably showed a diffusely diseased aorta, with
      calcification, mural thrombus, and ulceration. CONCLUSIONS: Atheroembolization
      during cardiac surgical procedures has profound medical and economic
      consequences. Because of the diffuse nature of aortic disease, measures
      approaching the disease as a local process are likely to be unsuccessful.
      Appropriate evaluation would ideally identify patients with extensive aortic
      atheromatous disease, prior to rather than during surgery.

PMID- 10081312
TI  - [What is the utility of medical terminology?].
AB  - Studying medical language, medical terminology may appear as a rather marginal
      science for medical doctors and its use might appear at first side as relatively
      irrelevant. This article aims at giving some examples of the usefulness of
      medical terminology for medical practitioners.

PMID- 10081313
TI  - [How to investigate ... diffuse interstitial lung disease].
AB  - There are a large number of conditions of known or unknown causes that have a
      tendency to alveolar wall fibrosis. The patient usually presents with progressive
      dyspnoea and the chest radiograph shows bilateral shadows whereas physiological
      measurements show a restrictive defect. Because of implications with regard to
      treatment and prognosis, diagnosis and staging of the disease are important.
      Computed tomography ("high resolution") and bronchoalveolar lavage are very
      useful at all stages of management of interstitial lung disease.

PMID- 10081314
TI  - [Drug of the month. Sildenafil (Viagra)].
AB  - Sildenafil (Viagra) from Pfizer (UK-92,480) is a competitive and selective
      inhibitor of cyclic GMP specific type 5 phosphodiesterase. Male erectile
      dysfunction is defined as "the inability to attain and/or maintain penile
      erection sufficient for satisfactory sexual performance". Sildenafil (Viagra) is
      effective in a significant proportion of patients with erectile dysfunction.
      Patients should be instructed to take a dose from 25 to 100 mgrs approximately 30
      to 60 minutes before sexual activity, but no more than once daily. Sexual
      stimulation is necessary to produce erectile reaction. The safety and tolerance
      of sildenafil have been demonstrated. However, prior to initiating treatment with
      sildenafil, physicians should consider the cardiovascular status of their
      patients, particularly for patients with unstable coronary heart disease or
      concomitant treatment with nitrates.

PMID- 10081315
TI  - [Pharma-clinics. The drug of the month. Aceclofenac (Biofenac)].
AB  - Aceclofenac, a phenylacetic acid derivative, is a new nonsteroidal anti
      inflammatory drug (NSAID). It is indicated in the symptomatic treatment of pain
      and inflammatory or degenerative arthropathies: osteoarthritis, rheumatoid
      arthritis, ankylosing spondylitis, abarticular inflammations, posttrauma or
      postoperative inflammations. The usual oral dosage of aceclofenac is 100 mg twice
      daily in adults. Its clinical efficacy seems to be similar to that of other
      NSAIDs, but its safety profile, especially gastro-intestinal tolerance, appears
      to be better. Finally, in vitro studies suggested that aceclofenac may exert
      positive effect on cartilage matrix metabolism.

PMID- 10081316
TI  - [Direct myocardial revascularization from an upper median laparotomy in a
      reoperation].
AB  - Case-history of a patient with IHD, six months after the first revascularization
      operation, performed on account of occluded venous grafts and relapse of anginous
      complaints, successfully reoperated from upper median laparotomy. From this
      surgical approach an anastomosis of the right gastroepiploic artery on the ramus
      interventricularis posterior (RIVP) of the right coronary artery was made. Six
      months after operation the patient is free from angionous complaints and lives a
      full life. Control coronarograpy indicates patency of the graft.

PMID- 10081317
TI  - [Plastic surgery of the thoracic wall as a method of thoracic wall reconstruction
      after complete surgical wound disintegration after sternotomy].
AB  - During the period between January 1996 and July 1998 in our department 1920
      patients were operated on account of heart disease from median sternotomy. In 17
      patients, i.e. in 0.9% during the early postoperative period the surgical wound
      disintegrated incl. dehiscence of the sternum and the development of
      postoperative mediastinitis. In 14 of these patients the authors reconstructed
      the defect of the thoracic wall by their own modification of Jurkiewicz plastic
      operation using the pectoral muscles. One patient from this group died, in the
      remaining 13 patients the wound healed without deformity of the chest and without
      signs of instability, without restriction of movement and function.

PMID- 10081318
TI  - [Eversion endarterectomy of the internal carotid artery].
AB  - Eversive endarterectomy of the internal carotid artery is an alternative method
      of conventional endarterectomy from a longitudinal incision. It resolves
      ulcerative and stenotic affections of the artery along with possible correction
      of the associated elongation. The operation creates favourable haemodynamic
      conditions in the area of the carotid circulation.

PMID- 10081319
TI  - [Aneurysm as a complication of arteriovenous anastomoses for hemodialysis].
AB  - Angioaccess procedures for hemodialysis over a 12-year period were
      retrospectively reviewed to ascertain the frequency of aneurysm complications. A
      total of 571 angioaccess procedures were performed including 88
      polytetrafluoroethylene grafts. 1.24% autogenous fistulae and 5.7% ePTFE grafts
      had uncomplicated aneurysm. Complicated (thrombosis, bleeding, infection)
      aneurysm occurred in 5.2% autogenous fistulae and in 5.7% PTFE grafts. The
      authors recommend a surgical repair of all angioaccess-associated aneurysms in
      the time of uncomplicated occurrence. If the aneurysm is complicated, the risk of
      the function lose of the av shunt by surgical therapy increase.

PMID- 10081320
TI  - [Congenital thrombosis of the aortic arch simulating aortic coarctation in a
      neonate].
AB  - The authors present the case-history of a two-day-old neonate with clinical signs
      of critical coarctation of the aorta where echocardiography revealed thrombosis
      of the aortic arch and isthmus. By surgery it was impossible to remove the
      organized thrombus from the aorta, therefore the portion of the aorta with the
      thrombus was resected and the aorta was reconstructed by an end-to-end
      anastomosis. After surgery long-term anticoagulation treatment with Warfarin was
      started. Examination of haemocoagulation factors, incl. proteins C and S and
      antithrombin III revealed normal findings. The test for lupus erythematosus was
      also negative. From the case-history of the mother's pregnancy the cause of the
      serious congenital aortic thrombosis could not be traced. The child is all right
      after surgery and thrives.

PMID- 10081321
TI  - [Conversion of drainage of a pancreatic transplant from the urinary bladder to
      the intestine in a recipient].
AB  - The most frequently used surgical technique in transplantations of the pancreas
      is to connect the duodenum of the graft with the urinary bladder of the
      recipient. Introduction of this method led during the last five years to marked
      improvement of results. On the other hand duodenocystoanastomosis is a frequent
      cause of metabolic and urological complications in patients after
      transplantation. The authors present the case-record of a female patient after
      combined transplantation of the pancreas and kidney where surgical conversion of
      the drainage of pancreatic juice from the urinary bladder to the gut was
      necessary.

PMID- 10081322
TI  - [The changing clinical picture of gastroduodenal ulcer disease].
AB  - OBJECTIVE: The authors evaluate the changing clinical picture of gastroduodenal
      ulceration in recent years. METHOD: They analysed their own clinical material
      from January 1994 till April 1998 when at the Second Surgical Clinic in Olomouc
      188 patients were hospitalised on account of gastroduodenal ulceration. RESULTS:
      The group of patients comprised a high proportion of patients above 60 years of
      age (102, i.e. 55%) and twice as many cases of duodenal ulcers as compared with
      gastric ones. In 4% ulcers were present at both sites. In 92% (173 patients)
      acute admissions were involved and only in 8% (15 patients a planned admission
      for elective treatment was involved. As to complications haemorrhage was most
      frequent (84%), perforations in 13% and pylorostenosis in 3%. Of the acute
      admissions 56 patients were operated, i.e. 32%, the rest were treated by
      conservative methods. The surgical lethality was 12%, the lethality of the
      conservatively treated patients 5%. CONCLUSION: Gastroduodenal ulceration is at
      present characterised by a predominance of conservative treatment, a decline of
      elective operations, a high percentage of complications in particular in advanced
      age, more frequent affection of the duodenum and late indication for surgery,
      when conservative treatment is not very successful.

PMID- 10081323
TI  - [All-in-one parenteral nutrition and enteral nutrition--experience and risks in
      surgical clinical practice].
AB  - The author presents an account on total parenteral nutrition "all-in-one" used in
      his department in a group of 479 patients, and enteral nutrition in a group of 98
      patients in 1995-1997. When the two methods were used, the patients' nutritional
      status was maintained or improved, while the risk of remediable complications is
      small. The optimal strategy of postoperative nutritional support is a combination
      of the two methods. Enteral nutrition makes physiological rereplations during
      administration possible and reduces the risk of septic complications.

PMID- 10081324
TI  - [Endosonographic staging of rectal tumors in a surgical department].
AB  - In 1997 and 1998 the authors implemented and evaluated endosonographic
      examinations of the rectum in 34 patients, incl. 22 on account of carcinoma and
      12 for adenoma. Carcinomas classification T1 were recorded in 9%, T2 in 27.3%, T3
      in 54.5% and T4 in 9%. Agreement with histopathological staging was recorded in
      63.6%. In adenomas in 17% a suspect malignant appearance and spread into the
      muscularis propria was found and this was confirmed by histological examination.
      The results confirmed the contribution of routine endosonographic examinations to
      accurate staging and subsequent indication of different therapeutic modalities.
      From the surgical aspect it is important for assessment of the stage T4 and thus
      also primary inoperability. The examination is valuable also when it is
      impossible to visualize highly located tumours, as it rules out infiltration of
      adjacent organs.

PMID- 10081325
TI  - [Solitary rectal ulcer].
AB  - The solitary rectal ulcer syndrome describes a condition in which a symptom
      complex consists of rectal bleeding, mucous discharge, tenesmus, perineal or
      abdominal pain, a feeling of obstructed defecation and incomplete evacuation and
      developing of rectal stenosis. The etiology of this disease is not known yet. The
      histological diagnosis is very important, because of excluding the diagnosis of
      malignancy. According to diagnostic results, the type of therapeutic method is
      used. The initial conservative methods are suggested in every time. In the case
      of failure of this method, the surgical procedure is chosen. An operative
      specimen must be histologically investigated in every case.

PMID- 10081326
TI  - [Use of genetic methods in the detection of pathogens in complications of
      extensive surgical procedures].
AB  - The method of the polymerase chain reaction (PCR) is used in the detection of
      septic conditions and monitoring of infectious agents in asymptomatic patients
      after organ transplantations and extensive cardiosurgical operations. The method
      allows semiquantitative and quantitative detection of bacteria, micromycetes and
      viruses and from the systematic quantitative follow-up of pathogen levels it is
      possible to draw conclusions on the prognosis of the patients condition or the
      success of the therapeutic procedure. The author demonstrates on practical
      examples of examined patients the possibilities of the method as compared with
      hitherto used ones. As examples two patients are quoted after surgery of a valve
      on account of bacterial endocarditis and three patients after transplantation of
      life important organs where the presence if cytomegalovirus was detected.

PMID- 10081327
TI  - [Systemic enzyme therapy in the treatment of supracondylar fractures of the
      humerus in children].
AB  - The authors present their experience with enzyme therapy--the preparation
      Wobenzym--in comprehensive treatment of supracondylar fractures of the humerus in
      children. On monitoring the condition of the extremity by Doppler ultrasound,
      where the flow through the radial artery was quantified they obtained better
      results in the group of patients treated by systemic enzyme therapy than in the
      control group. Systemic enzyme therapy is recommended as a suitable supplement in
      comprehensive treatment where the most important part is played by correct and
      early treatment along with precise monitoring of the extremity during the
      postoperative course.

PMID- 10081328
TI  - [A new vaccination plan in Mexico].

PMID- 10081329
TI  - [Alcoholic beverage consumption in the patients of the emergency services of the
      city of Pachuca, Hidalgo].
AB  - OBJECTIVE: Prevalence of alcohol consumption and abuse among patients with
      medical emergencies, accidents and violence, attending an emergency room in one
      of three public health hospitals in Pachuca, Hidalgo, was studied. MATERIAL AND
      METHODS: Patients answered a questionnaire and their blood alcohol was measured
      on their first visit to the emergency room. The questionnaire gathered socio
      demographic data, patterns of alcohol consumption and included scales for heavy
      and dependent drinkers, such as the CAGE and the alcohol use disorders
      identification test (AUDIT). Injured and non-injured patients were compared with
      the chi 2 statistics. RESULTS: A total of 1,511 patients were evaluated. Alcohol
      consumption was higher in those attending for accidents or violence than in
      medical patients. Positive blood alcohol levels were found in 17.7% of injured
      patients and 15.8% reported alcohol consumption 6 hours prior to the accident.
      According to the CAGE, 9.2% of the patients were alcohol-dependent, and 10.9%
      were heavy drinkers according to the AUDIT. CONCLUSIONS: Alcohol consumption,
      especially among emergency room patients attending for accidents or injuries is
      high. Preventive measures are indispensable to diminish social and individual
      costs of alcohol abuse in this population.

PMID- 10081330
TI  - [Electrocardiographic changes and cardiovascular risk factors in patients with
      type-2 diabetes].
AB  - OBJECTIVE: To determine the most frequent alterations in rhythm and cardiac
      conduction in patients with type 2 diabetes without previous cardiopathy, and to
      establish the association of this disease with cardiovascular risk factors.
      MATERIAL AND METHODS: Subjects with type 2 diabetes, without cardiopathy
      antecedents were included in the study. Cardiovascular risk factors, body mass
      index and serum glucose, cholesterol and trygliceride levels were determined. A
      resting electrocardiogram was recorded. The association between the variables
      under study and arrhythmia was calculated with a multivariate analysis adjusted
      by sex. RESULTS: A total of 199 patients were included: 113 women (56.8%) and 86
      men (43.2%). Arrhythmia was registered in 29.1% of the subjects. Anterior
      hemiblock (AH) and right bundle branch block (RBBB) constituted 75.9% of the
      identified alterations. Patients with arrhythmia and conduction disorders have
      higher levels of cholesterol and triglycerides. Appearance of arrhythmia is
      directly related to aging (r = 0.75, p = 0.01). The multivariate analysis
      adjusted by sex revealed that hypercholesterolemia and aging are significantly
      associated with arrhythmia and conduction alterations: OR 1.5, CI 95%, 1.1-4.6, p
      < 0.05 and OR 1.3, CI 95% 1.0-5.2, p < 0.05, respectively. CONCLUSIONS: The most
      frequent arrhythmia and conduction disorders in type 2 diabetes are AH and RBBB.
      Hypercholesterolemia and aging are the strongest and most frequent factors
      associated to the presence of this disease.

PMID- 10081331
TI  - [Ambulatory medical care in Mexico: the cost for users].
AB  - OBJECTIVE: To analyze the results of the National Health Survey (ENSA-II) as to
      the costs generated by the search and obtainment of ambulatory medical attention
      in various institutions of the private and public health sector. MATERIAL AND
      METHODS: Information was raised from the health care cost indicators reported by
      the study population of the ENSA-II. The dependent variable was the direct
      expense for the consumer and the independent variables, the condition of being
      insured and the income. Variation significance levels were identified using the
      test by Duncan. RESULTS: The costs at national level in US dollar were: transport
      $2.20, medical visit $7.90, drugs $9.60, diagnostic studies $13.6; average total
      cost for ambulatory attention was $22.70. Empirical finding suggest a new direct
      and indirect cost-for-consumer analysis for the health care users. These costs
      represent an important burden on the family income, which worsens when users are
      not insured. CONCLUSIONS: Incorporation of the economic perspective to the
      analysis of public health issues should not be limited to the analysis of the
      health provider's expenses, particularly if the problems of equity and
      accessibility must be solved, which are at present characteristic of health care
      services in Mexico.

PMID- 10081332
TI  - [A proposed open formulary for a managed care program in Mexico. The Therapeutic
      and Pharmacological Committee of Mexico].
AB  - OBJECTIVE: To integrate an open formulary with drug use recommendations in which
      a physician could find a wide range of therapeutic options for his private
      practice. MATERIAL AND METHODS: An interdisciplinary medical committee with a
      high scientific level, reviewed each one of all the drugs available to be sell in
      Mexico, as part of a Pharmacy Benefit Management & Manage Care program
      implemented in our country. Each drug was classified according to its active
      ingredient under one of the following categories: 1) essentials, 2) excluded, and
      3) not essentials-not excluded. The decision in each case was based on pure
      scientific grounds and using an Evidence-Based Medicine analysis. RESULTS: The
      proposed formulary contains a total of 1106 active ingredients-either unique or
      in combination-, from which 429 (38.8%) were classified as essentials. About one
      out-of-ten drugs (8.7%) currently in use within the private medical practice in
      Mexico, some of them highly prescribed, were regarded by the committee as
      excluded due to concerns about their efficacy and/or safety. CONCLUSIONS: On this
      report a detailed description of the process followed to conform the committee,
      its objectives an its performing criteria is presented, as well as the bases
      under which the final list of drugs of the formulary were set.

PMID- 10081333
TI  - [Occupational exposure to inorganic lead in a printing plant in Mexico City].
AB  - OBJECTIVE: To describe occupational lead exposure and its biological indicators
      in workers in a printing company. MATERIAL AND METHODS: An epidemiological and
      industrial hygiene research was undertaken. Lead was measured in the air of work
      environment and on the hands of the participants; additionally, subjects
      underwent a venous blood samples for the determination of whole blood lead by
      atomic absorption spectrophotometry; and a bone lead measurement using a spot
      source 109Cd K-X-ray fluorescence instrument. Also, a standardized questionnaire
      was applied. We obtained information on demographic and life styles factors, work
      history, type of work, position and activity within the company. RESULTS: Of the
      209 workers, 117 agreed to participate and 90 (83.3% males and 16.7% females)
      completed all phases of the study. The average lead concentrations were: in air
      samples, of 0.94 microgram/m3; in hands before washing, of 6,802 micrograms/m2;
      in hands after washing, of 194 micrograms/m2; in whole blood, of 12.3
      micrograms/dl; and in tibia and fibula, of 25.9 and 43.3 micrograms Pb/g of bone
      mineral, respectively. Important variations in these measurements were observed
      according to the workers post. CONCLUSIONS: Worldwide, lead exposure levels have
      been used to evaluate acute exposures being in the workplace. The higher lead
      levels find in the bone of the workers in this study are similar to other
      occupational studies in the United States of America and suggest that the
      accumulated metal in bone may be an important endogenous exposure source, and
      here its measurement importance. However in developing countries because its high
      costs per application, the measurements in bone lead become limited to
      epidemiological research, although not as an instrument for occupational
      epidemiological surveillance. In Mexico, there are no reliable studies of
      occupational lead exposure, which would allow the establishment of both, maximum
      permissible ambient and biological levels. This study is intended to contribute
      to blood lead standard setting, which is being discussed in Mexico.

PMID- 10081334
TI  - [Persistent symptomatology in workers industrially exposed to organophosphate
      pesticides].
AB  - OBJECTIVE: To describe the patterns of persistent symptomatology in workers
      industrially exposed to organophosphate pesticides. MATERIAL AND METHODS: An
      observational, descriptive and cross-sectional study was performed. A
      questionnaire was applied to managers of a factory and to 89 workers, whose
      erythrocytic cholinesterase level was measured with the Magnotti and Lovibond
      method. Information is described through rates, central tendency measures and
      dispersion. Differences between groups were evaluated with the chi 2 test and the
      odds ratio was calculated. RESULTS: Persistent symptomatology was found in 6.3
      per 10 workers. 50% had six or more symptoms. No significant differences were
      found as to the risk of suffering from persistent symptomatology with respect to
      age, length of service or position at work. However, the highest proportion of
      symptoms was found in workers of 31 to 40 years of age, with 6 to 13 years of
      service, from the maintenance area, working as general operators or supervisors.
      Among the 13 workers with previous intoxication, the prevalence of persistent
      symptomatology was 6.9 against 6.1 in workers who had not been intoxicated
      before. The risk of acute poisoning in workers with more than 14 years of service
      was 4 times greater than in workers with less than 14 years of service (p <
      0.005). Average level of blood cholinesterase was normal (4.4 u/ml). CONCLUSIONS:
      Results show a relationship between exposure to organophosphate pesticides and
      presence of persistent symptoms. It is necessary to study the prevalence of this
      symptomatology in exposed and non-exposed populations.

PMID- 10081335
TI  - [The balance for 1998].

PMID- 10081336
TI  - [Asthma].

PMID- 10081337
TI  - [The main results from the statistics on mortality due to accidents in Mexico,
      1997].

PMID- 10081338
TI  - [Indications and results of thyroid gland ultrasound imaging of ambulatory care
      patients].
AB  - Sonography permits investigations which furnish impressive information whose
      practical benefit for the patient, however, has not been documented so far. The
      thyroid lends itself extremely well to sonographic study because of its
      superficial localization. The efficiency of this investigation has also not been
      elucidated. This study addresses the question of correlation between clinical and
      sonographic examination. Sonographic imaging did not have a great clinical impact
      and therapeutic consequences were rarely generated. A definitive diagnosis was
      usually possible after fine needle aspiration or hormonal analysis. Solitary
      thyroid nodules are an indication for sonography. Whether sonography is useful in
      patients with euthyreotic nodular goiter is debatable.

PMID- 10081339
TI  - [Heart failure and treatment of ventricular arrhythmias].
AB  - Chronic heart failure (CHF) is generally associated with a poor prognosis with an
      annual mortality rate ranging between 15-50% depending on the severity of cardiac
      dysfunction thus presenting a major health problem in our society. Drugs for the
      treatment of CHF include vasodilators (ACE-inhibitors, angiotensin II receptor
      blockers), diuretics, digoxin and beta-blockers. However, antiarrhythmic drugs
      are not currently recommended in the management of CHF with the exception of beta
      blockers for which a favorable effect on the prognosis could be shown. Amiodarone
      is effective in the suppression of ventricular arrhythmias without a significant
      effect on total mortality. Implanted defibrillators are superior to
      antiarrhythmic drug therapy in prolonging survival among survivors of sudden
      cardiac death. They should be offered as firstline therapy in case of life
      threatening ventricular tachy-arrhythmias.

PMID- 10081340
TI  - [More tolerance in management of unmotivated elderly family members].
AB  - The elderly frequently experiences demotivation as a sign of depression.
      Demotivation often results in failures of relationships and isolation increases
      confusion of the demotivated individuals who are often additionally impaired by
      physical illness or its sequels. The elderly exposes himself to an affective
      dependence on engaged services or relationships. Motivation is also threatened by
      consequences of physical dependence which alters self-esteem. The difficulty to
      adapt to new situations adds up with poor social integration in an increasingly
      complex environment. This often precludes loss of ability to execute personal
      decisions and to cope with daily activities. This all accentuates dependence and
      depression and promotes further withdrawal. Impairment of cognitive functions and
      withdrawal increase the burden of familial suffering. We propose solutions
      adapted to demotivated elderly people in order to reintegrate them in their
      family and daily life.

PMID- 10081341
TI  - [PET activation studies with cerebral reorganization of movement].

PMID- 10081342
TI  - [Recurrent hyponatremia, neurological symptoms and long-term administration of
      levomepromazine].
AB  - We present the case of an 84 year old lady with an episode of marked hyponatremia
      with acute neurological disturbances which in the latest case resolved completely
      after a 3 day period of fluid restriction. The more common causes of hyponatremia
      could be ruled out. There was no evidence for a neuroleptic drug associated
      change in serum sodium concentration. We conclude that the patient in this study
      belongs to a subset of geriatric patients in whom there is an intermittent SIADH
      which only becomes clinically evident when several factors coincide. The
      underlying mechanisms are not understood but could include the interaction of
      subclinical cerebrovascular disease and treatment with a neuroleptic drug in an
      elderly patient whose water and sodium homeostasis is compromised by the changes
      of normal aging which affect the many systems involved in maintaining water and
      sodium balance.

PMID- 10081343
TI  - [Psoriatic arthritis without psoriasis].

PMID- 10081344
TI  - [Contraception and abortions].

PMID- 10081345
TI  - [Who shall be treated for excessive sweating and how?].

PMID- 10081346
TI  - [Registration of births and newborn infants in Norway].

PMID- 10081347
TI  - [Children with birth weight 1500 g or under from Troms and Finnmark in the period
      1978-1989].
AB  - During 1978-89, 245 women in Troms and Finnmark counties gave birth to 265
      liveborn with birth weight < or = 1,500 g. The incidence of liveborn < or = 1,500
      g, and of live- and stillborn < or = 1,500 g did not change significantly during
      the study period, but the stillborn proportion of live- and stillborn < or =
      1,500 g decreased. The proportion of patients that had intrauterine transfer to
      hospitals with neonatal intensive care unit (72%), and neonatal transport (17%)
      did not change significantly. The mortality rate was constant (34%), probably due
      to change in registration practice leading to an increase in liveborn < or = 750
      g. The handicap rate at four years of age decreased from 21% in 1978-81 to 12% in
      1986-89, although the rates of moderate (8%) and severe (2%) handicap were
      unchanged. Cerebral palsy occurred in 10%, and blindness due to retinopathy of
      prematurity in 1%. The results are compatible with those of other studies from
      the same period.

PMID- 10081348
TI  - [Children with birth weight 1500 g or under from Nordland in the period 1978
      1989].
AB  - All 271 liveborn infants with birthweight < or = 1,500 g born of mothers residing
      in Nordland county during 1978-89 were studied retrospectively. Mean birthweight
      was 1,083 g, mean gestational age 29 weeks and 21% of the children were growth
      retarded. 18% of the newborns were transported from local hospitals to a neonatal
      intensive care unit, most of them (82%) by the unit's transport team. The number
      of infants delivered by caesarean section increased during the study period. 103
      children (38%) died before the age of four. 15 children (6%) died after the
      newborn period, mostly due to bronchopulmonary dysplasia (n = 8) and sudden
      infant death syndrome (n = 4). Mortality rate corrected for birthweight < or =
      500 g, lethal malformations and sudden infant death syndrome was 32%. The
      proportion of liveborn children suffering from cerebral palsy was 4.8%. Although
      the mortality rate remained unchanged during the study period, the proportion of
      disabilities decreased.

PMID- 10081349
TI  - [Drug use in a neonatal unit].
AB  - All medication administered to patients admitted to a neonatal intensive care
      unit was registered during a one-year period (1996). Only two (0.4%) of 469
      infants admitted were not given any drug at all. A total of 12,019 single doses
      were administered, a mean of 33 per day. 7,042 (59%) were given orally, and 3,332
      (28%) intravenously. 292 (63%) patients were given vitamin K as the only drug.
      113 infants (24%) received systemic antibiotic treatment, 5% of all infants born
      alive at the hospital. Drugs accounted for 2.7% of the total expenses for running
      the unit. Surfactant (12 single doses) alone accounted for 47% of the costs of
      drugs. Drug monitoring by serum concentration measurements showed that 32% of the
      values were outside the therapeutic range. To a limited extent (44%) this was
      followed by correction of the dose. One single drug dose (1 per 10,000 doses) was
      administered to a patient for whom the drug was not prescribed. Quality assurance
      of medication is an important task in neonatal intensive care units.

PMID- 10081350
TI  - [Not using contraception among women requesting abortion].
AB  - The aim of this survey was to examine the number of abortion applicants not using
      contraception at the time of conception, to shed light on the reasons for this,
      and to acquire information about the knowledge of postcoital anticonception in
      this patient group. The registered data is collected from precoded medical
      records at the University Hospital of Trondheim comprising 2,074 women applying
      for abortion in the period 1.1. 1995-15.7. 1997. The 291 applying for abortion
      15.1-15.7. 1997, and who had not used contraception were given a questionnaire.
      160 (55%) answered the questionnaire. During the period of 2.5 years 57.4% had
      not used contraception at the time of conception. The tendency of non-use has
      increased significantly during the last 2.5 years. Concern about sideeffects was
      the most common reason for not using contraceptives (36%). One third trusted the
      rhythm method and coitus interruptus. The postcoital pill was known by 93%; of
      the 61 women who had considered using it, 67% thought of it too late. To prevent
      unwanted pregnancies, it is important to focus on the positive health effects of
      oral contraception. Information efforts should especially be aimed at young and
      single women, who represent the majority of the non-users. The cost is no great
      impediment to the use of contraception. Availability of emergency contraception
      should be improved.

PMID- 10081351
TI  - [HTLV examination of Norwegian blood donors].
AB  - Approximately one third of the Norwegian blood donor population has been tested
      for infection with human T-lymphotropic virus type I and II (HTLV-I/II). This
      study was initiated to provide an indication as to whether or not the Norwegian
      transfusion service should screen the entire donor population for HTLV I/II. No
      HTLV-I infections were found among the blood donors. One new donor was confirmed
      HTLV-II positive. This individual had previously used drugs intravenously. HTLV
      I/II infection can be regarded as a marker for risk behaviour, and testing can be
      of significance in the quality assurance of the transfusion service. We recommend
      that the entire blood donor population be tested for HTLV-I/II infections, and
      thereafter only new donors. The benefit of this scheme should be evaluated in the
      future.

PMID- 10081352
TI  - [Chronic heart or lung disease and psychosocial stress].
AB  - Ten boys and 15 girls below the age of 16, were referred to the National Hospital
      in Norway for evaluation for heart or lung transplantation 1990-97. 24 of the
      children and their families went through a thorough psychosocial assessment in
      order to assess the supportive measures the children and their families might
      need for coping with stress during the evaluation and the follow-up period. The
      patients were divided into three diagnostic groups: Two had cystic fibrosis and
      one an obstructive lung disease, heart-lung group, eight had congenital heart
      disease and 13 cardiomyopathy. 15 children were accepted for transplantation and
      placed on the waiting list. The others were rejected for medical reasons. Seven
      children (29%) filled the criteria for a psychiatric diagnosis (six anxiety
      disorders and one depression). Five others had considerable anxiety symptoms. The
      cardiomyopathy group had fewer problems than the heart-lung and congenital heart
      disease groups. The study shows that families with children suffering from life
      threatening disease live with a great deal of stress and are in need of help and
      support. Many families are either not aware of their rights or too exhausted to
      seek help.

PMID- 10081353
TI  - [Problematic puberty?].
AB  - This paper shows how involvement in problem behaviour among 13- and 14-year-olds
      varies according to level of pubertal development. Furthermore, it explores
      whether psychosocial factors such as characteristics of the peer network
      (deviance and gang membership), parental behaviour (supervision, care, and
      parents' frequency of alcohol intoxication) and masculine gender identity mediate
      this relationship. The data stem from a nation-wide representative survey of the
      general youth population in Norway (n = 3,139, response rate 97%). The prevalence
      of problem behaviour (i.e. shoplifting, truancy, vandalism etc.) increased with
      increasing levels of physical maturation for both sexes. The association was
      strongest among boys, however. Further analyses revealed that this gender
      difference could be attributed to the fact that early mature boys, to a greater
      extent than early mature girls, associate with deviant peers.

PMID- 10081354
TI  - [Rheumatoid arthritis and heart disease].
AB  - Rheumatoid arthritis is a chronic inflammatory disease that usually involves the
      joints, tendons and bursae. The disease is systemic and may involve the brain,
      peripheral nerves, lungs, kidneys, heart and blood-vessels. All anatomical
      structures of the heart may be involved. Most reports on rheumatoid arthritis and
      heart disease are case reports and autopsy studies. Sonography studies from
      recent years show pathology in some heart structures at about the same rate as
      autopsy studies. Mortality studies from the last ten years provide evidence of
      increased cardiovascular mortality. The frequency of reported rheumatoid heart
      disease differs according to the method applied in the studies. Clinically
      significant disease is infrequent. We describe two cases with pericarditis and
      give a review of the literature.

PMID- 10081355
TI  - [The complement system--structure, activation, regulation and function].
AB  - Activation of the complement system plays a key role in normal inflammatory
      response to injury but may cause substantial injury when activated
      inappropriately. The cascade is activated through classical, alternative and
      lectin pathways. The human complement system is in most cases well controlled by
      the host, and inappropriate activation and host cell destruction are prevented.
      The control is mainly mediated by complement regulatory proteins. The use of
      powerful methodologies in molecular biology, biochemistry and physiology has led
      to impressive advances in our knowledge of the mechanisms of complement
      activation and regulation and its role as either a protective or pathogenic
      factor in human disease. With respect to disease pathogenesis, the complexity of
      the cascades provides opportunities for several different therapeutic targets
      within the pathways, and we are about to witness the availability of a variety of
      complement modulators for specific therapies. This article reviews biological
      aspects of this important immunological effector mechanism.

PMID- 10081356
TI  - [Should pethidine still be administered to women in labor?].
AB  - According to surveys from 1988, 1992 and 1996, Norwegian obstetric departments
      are still to a large extent using pethidine as birth analgesia. In this article
      we report recent knowledge of various pharmacological effects of pethidine in
      mothers and newborns. Pethidine has mainly a sedative effect, but very little
      analgesic effect in parturients. Pethidine has relatively long-acting behavioural
      and neurological effects in the newborn due to slow elimination. As a result,
      breastfeeding is delayed and the mother-infant interaction is disturbed according
      to recent studies. There is concern about the more or less routine administration
      of pethidine in many hospitals. We conclude that obstetric departments should
      reconsider their use of pethidine.

PMID- 10081357
TI  - [Methadone used in the treatment of opioid dependence].
AB  - Norway has been a stronghold of restrictive attitudes and scepticism towards the
      use of methadone in treatment of heroin addiction. A policy of nation-wide use of
      methadone has now been adopted. This paper gives a short history of the use of
      methadone, a review of present neurobiological knowledge and a description of the
      different approaches in methadone based treatment. Methadone treatment does not
      reduce opioid dependency but compensates for neurobiological complications of
      long-term use. This increases the ability to profit from psychosocial approaches
      in treatment and reduces the tendency to risk-taking and socially disturbing
      behaviour. Norway aims to follow the "Swedish" model in methadone policy with
      emphasis on high threshold, high dose treatment combined with control and
      systematic rehabilitative measures. This choice should be evaluated both in a
      comparative and in a treatment oriented perspective.

PMID- 10081358
TI  - [The Oslo methadone project].
AB  - Of a total of 161 patients referred to a high threshold methadone project, 50
      patients with an average age of 37 years and more than ten years of heroine use
      were included. Retention was 72% after three years, none had died by overdoses
      during methadone treatment, and criminality and prostitution were negligible. The
      overdose mortality was significantly reduced compared to those on waiting list
      while the difference in mortality from all causes was less convincing. Drug
      taking continued for a considerable portion of the patients, and continued
      control and follow-up was necessary. Methadone cannot replace other types of
      treatment, but is a valuable contribution when such treatment is integrated in a
      comprehensive management. Active rehabilitation efforts are essential.

PMID- 10081359
TI  - [Increase in fatal cases among narcotic addicts--do we know why?].

PMID- 10081360
TI  - [Sexualization in therapeutic relations].

PMID- 10081361
TI  - [Routines ordered by law for testing of potential disease transmission are not
      sufficient].

PMID- 10081362
TI  - [Children in day care centers--antibacterial agents instead of good infection
      control?].

PMID- 10081363
TI  - [Antipsychotic agents--not to patients with dementia?].

PMID- 10081364
TI  - [Magnetic tomography and the central nervous system].

PMID- 10081365
TI  - [When the memory becomes troublesome].

PMID- 10081366
TI  - [Family practice in local municipalities--safety and responsibility].

PMID- 10081367
TI  - [The mystery of physician shortage--can it be solved?].

PMID- 10081368
TI  - [Children of psychiatry].

PMID- 10081369
TI  - [Research publication, the faculties, the Tidsskrift].

PMID- 10081370
TI  - [Are electromagnetic fields created by electric means hazardous to health?].

PMID- 10081371
TI  - [Creatinine and calcium in urine and blood after brief exposure to magnetic
      fields].
AB  - In this experimental study, 35 males were exposed to artificial magnetic fields.
      The fields were produced by a set of Helmholz coils internally isolated by a
      Faraday cage which effectively eliminated electrical fields. Each participant
      stayed inside the coils for 40 minutes on two occasions with an interval of seven
      days, but was actually only once exposed to a static magnetic field (9.6 mT) and
      oscillating magnetic fields of variable frequency and strength. Urine and blood
      samples were taken before and after exposure, and before and after non-exposure.
      Analysis detected significant changes in serum creatinine level after exposure (p
      < 0.0001). The changes in serum creatinine level in the nonexposed situation were
      significantly smaller than the changes found in the exposed situation (p <
      0.0001). The changes i urine creatinine after 40 minutes of exposure was also
      found to be significant (p < 0.01). Exposure to magnetic fields may induce
      biological reactions.

PMID- 10081372
TI  - [Adults treated as children for acute lymphocytic leukemia--methotrexate, late
      effects and quality of life].
AB  - From 1975 to 1980, 153 Norwegian children were diagnosed with acute lymphocytic
      leukaemia. In 1995, all 98 survivors were studied and compared to matched family
      controls. 132 children were treated with the national protocol. Of these, 93
      (70.5%) were survivors at the time of the study. The remaining five survivors
      were treated with different treatment schemes. The national protocol included
      methotrexate infusions combined with intrathecal methotrexate as prophylactics
      against neuroleukaemia, instead of the irradiation. Neither doxorubicin nor
      cyclophosphamide were included. In this study, a questionnaire was used that
      covered demographic data, quality of life, and medical information the response
      rates were 96% (94 persons) for survivors and 92% (90 persons) for family
      controls. Information was also obtained for the remaining four survivors. No
      significant differences were found between survivors and controls with regard to
      quality of life and demographics, with one exception, Somatisation on the GHQ-28.
      Hospital records of all patients were checked for possible late effects. One case
      of serious sequela (hemiparesis during therapy) was found, probably related to
      methotrexate therapy. Seven other serious, possible sequelae were recorded, but
      probably not related to methotrexate. There were no cases of secondary malignant
      neoplasm.

PMID- 10081373
TI  - [Guillain-Barre syndrome. Current treatment principles in the light of clinical
      aspects].
AB  - The Guillain-Barre's syndrome, or acute polyradiculoneuropathy, is a monophasic
      neurological disease affecting 50-100 persons a year in Norway. In addition to
      peripheral paresis, respiratory and autonomic disturbances may occur. We present
      22 patients, mean age 34.8 years, including four children between four and six
      years of age, who all received plasma exchange treatment. All our patients
      reported symptoms of a modest infection average 19 days before the neurological
      symptoms appeared. All patients had walking difficulties, half of them were
      unable to walk without assistance. There were cranial nerve findings in 18
      patients, and nine had autonomic disturbances when admitted. All except one had
      increased protein contents in the spinal fluid as well as pathological findings
      in electrophysiological investigations. They received on average 8.6 plasma
      exchanges. In spite of such treatment, the total mortality rate has not decreased
      substantially. Two of our patients died, and three developed severe permanent
      paresis. Further studies on pathogenesis will be required to increase treatment
      success.

PMID- 10081374
TI  - [Primary pulmonary hypertension in children].
AB  - Primary pulmonary hypertension is a clinical syndrome with severe pulmonary
      hypertension where other causal diseases are excluded. The condition is
      progressive, fatal and disappointingly resistant to therapy. In this article we
      present three children with the disease. Two of the patients died shortly after
      diagnosis, one of them during heart catheterization. The third patient showed
      good response to treatment with calcium channel blockers, diuretics and nightly
      supplementary oxygen. Quality of life and hemodynamics improved during the first
      six months of treatment, and remained virtually unchanged for another two years.
      Her condition then deteriorated rapidly, and she died three years after
      diagnosis. According to the literature and our experience, investigations with
      non-invasive methods such as oxygen saturation measurement, echocardiography, and
      a simple exercise test provide sufficient information to start therapy and
      monitor therapeutic response. Some patients show vasodilatory response to
      treatment with drugs, and might benefit from therapy with calcium channel
      blockers.

PMID- 10081375
TI  - [Villonodular synovitis--a rare condition causing intermittent locking of the
      knee].
AB  - Two patients with intermittent locking, mimicking a meniscal lesion or a loose
      body and with a palpable tumour in the knee joint are described. X-ray
      examinations were normal. Athroscopy revealed pedunculated tumours in both knees.
      The tumours were removed arthroscopically in one patient and by an arthrotomy in
      the other patient. The histological diagnosis was localized villonodular
      synovitis (giant-cell tumour) in both patients. This is a benign but very rare
      condition.

PMID- 10081376
TI  - [Measurement of glomerular filtration rate in connection with 99Tc-DTPA
      renography].
AB  - Glomerular filtration rate (GFR) was measured in two groups of cancer patients.
      In 20 patients, glomerular filtration rate was measured simultaneously with 51Cr
      EDTA, 99mTc-DTPA and the X-ray contrast agent iohexol as markers, and with a
      complete set of eight blood samples during 24 hours. In a second group of 120
      patients, we used 99mTc-DTPA only and tested various simplified methods, based on
      one or two blood samples. Glomerular filtration rate was also calculated from
      serum creatinine. There was excellent agreement between the values measured with
      the three markers, and, in the same group of patients, very good agreement with
      the results of simplified methods. The larger study carried out with 99mTc-DTPA
      on the second group of patients, confirmed a very good agreement between methods
      based on the slope of the plasma curve and a method based on one blood sample
      only. The correlation was worse between the values obtained by any of the
      radionuclide methods and those calculated from serum creatinine. The latter
      method should therefore not be used for determination of renal function.

PMID- 10081377
TI  - [Epilepsy in adolescence. Need for multi-professional diagnosis and treatment].
AB  - Epilepsy is one of the most common neurological disorders in adolescence. In a
      period of life which can be a trying time for anyone, unpredictable and
      stigmatizing seizures may create considerable additional problems for vulnerable
      teenagers. In recognition of the many problems young people with epilepsy may be
      facing, a special ward for teenagers at the National Center for Epilepsy was
      established. At this ward the patients are offered a broadspectered,
      multidisciplinary diagnostic and therapeutic programme. Patients with psychogenic
      seizures represent a particular challenge and are discussed in more detail.
      During the stay, patients attend an "epilepsy school" with instruction and
      discussions on topics related to epilepsy. This teenager ward has so far been a
      success and may serve as a transition clinic from child to adult care.

PMID- 10081378
TI  - [Methotrexate and folates in rheumatoid arthritis].
AB  - The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is
      well documented. Efficacy and adverse events are both dose dependent, and side
      effects rather than lack of response are the main reason for discontinuing
      therapy. Several adverse effects appear to be related to folate deficiencies, and
      are largely due to the antifolate properties of methotrexate. In order to
      diminish side effects without compromising drug efficacy, clinical trials have
      been performed using folic acid or folinic acid concomitantly with methotrexate.
      Important to this achievement are both the timing of folate supplementation and
      the weekly folate-to-methotrexate ratio. Considering these and other factors, an
      individually adjusted supply of folic acid is proposed. For several patients a
      properly balanced diet is sufficient; they do not need additional folate
      supplements when using methotrexate.

PMID- 10081379
TI  - [Severe hypophosphatemia--an overlooked condition?].
AB  - Severe hypophosphataemia is a well known metabolic disturbance, potentially
      serious. Clinicians are not always aware of this condition, which most likely is
      missed sometimes. We present a case in which severe hypophosphataemia was an
      important part of the clinical picture. An alcoholic was hospitalized because of
      epigastric pain, nausea and poor health. Seven days after admission he still was
      very weak and somnolent. He did not eat, and developed urinary retention due to
      paresis of the bladder. An extremely low level of s-phosphate, 0.12 mmol/l, was
      discovered the seventh day. The next two days he was substituted with 60 mmol
      phosphate i.v. At the same time his general condition improved dramatically. We
      believe that severe hypophosphataemia was an important cause of the persistently
      poor clinical condition of our patient. Finally, we present the causes of
      hypophosphataemia, stressing that serum phosphate does not always reflect total
      body phosphate. We discuss the possible manifestations of hypophosphataemia, and
      we give practical advice on treatment.

PMID- 10081380
TI  - [Is shortage of medical practitioners only a question of numbers? A
      phenomenologic approach to the scarcity of physicians in a county].
AB  - This paper presents a qualitative study of the employment of medical doctors in
      More and Romsdal County. On the basis of the fact that Norway has more physicians
      in relation to the population than other Northern European countries, we try to
      explore the reality behind the excessive demand for physicians? On the basis of
      interviews with physicians in hospitals and primary health care, we suggest four
      categories of explanations. First, areas with low population density experience a
      traditional scarcity of doctors. Second, a scarcity of doctors is locally
      constructed in municipalities with no excessive demand from patients for medical
      aid, but with vacant positions. Third, medical science generates a scarcity of
      doctors as medical specialisation has gone beyond the level needed for work in
      small hospitals. Fourth, there is a demand-driven scarcity of doctors caused by
      new treatments generating new patients. The four categories may differentiate the
      debate on how to solve the Norwegian problem of scarcity of medical doctors.

PMID- 10081381
TI  - [Medical practitioner staffing in 2010--four scenarios of medical practitioner
      staffing].

PMID- 10081382
TI  - [Autonomy promoting clinical work].

PMID- 10081383
TI  - [Health information in Manhattan and in Norway--what will become of the Norwegian
      efforts?].

PMID- 10081384
TI  - [All men over 40 years should take prostate-specific antigen].

PMID- 10081385
TI  - [Medical records on whiplash injuries].

PMID- 10081387
TI  - [Physician's competence].

PMID- 10081388
TI  - [Scarcity of physicians and hospitals--planning for the needs of yesterday].

PMID- 10081389
TI  - [Legal protection and attitude to disease].

PMID- 10081390
TI  - [Emergency diseases of the ear (comparative statistical data)].
AB  - Statistical data are detailed concerning compositional, therapeutic and
      diagnostic aspects of urgent diseases of the ear (inflammation and traumas of the
      external ear, acute and aggravated chronic otitis media, acute neurosensory
      hypoacusis, etc.). 580 patients were urgently hospitalized to ENT clinic (Moscow
      General Hospital N 1) at the Russian State Medical University in 1995 for urgent
      diseases of the external, middle and internal ear. This makes up 28% of a total
      of hospitalized ENT patients. The most effective policy of treatment for each ear
      disease form is analyzed.

PMID- 10081391
TI  - [Use of gaseous ozone and ozonized solutions in the treatment of chronic
      suppurative otitis media].
AB  - Ozone as gas and ozonized solutions were employed as treatment modalities in 28
      patients with acute and chronic inflammatory diseases of the middle ear. Basing
      on otoscopy, bacteriological tests of the discharge from the middle ear cavity,
      number of washings before disappearance of the purulent discharge the conclusion
      was made that cure of patients on ozone therapy occurs 3-5 days earlier than in
      ozone-untreated patients. Ozone therapy is a beneficial adjuvant in combined
      treatment of otitis media.

PMID- 10081392
TI  - [Alternating signal speech audiometry in the diagnosis of central lesions of the
      acoustic analyzer].
AB  - Diagnostic sensitivity was compared for two binaural methods of "sensitized"
      speech audiometry--alternating speech audiometry (ASA) and Dichotic. A total of
      35 patients were examined having neurosensory hypoacusis resultant from
      cerebrovascular atherosclerosis and chronic insufficiency of cerebral
      circulation. ASA indicated defects of the central parts of the acoustic analyzer
      in 80% of the examinees. The results of the two methods were similar in 85.7% of
      the patients. The diotic and dichotic alternating speech tests can be used
      separately and in combination in diagnosis of central acoustic disturbances, of
      vascular genesis, in particular.

PMID- 10081393
TI  - [Use of nonopiate agents for anesthesia in ENT patients at high surgical
      anesthesiological risk].
AB  - Optimal methods of endotracheal anesthesia using non-opiate drugs of four classes
      (clofelin, transamine, contrykal, ketanes) have been fundamentally grounded
      developed and tried in extensive and traumatic operations for ENT malignant and
      vascular tumors as well as inflammation in patients of high anesthesiological
      operative risk. The drugs were used in 174 patients including 13 children. 87.9%
      of the patients had concomitant diseases: blood hypertension, coronary heart
      disease, chronic nonspecific pulmonary diseases, bronchial asthma, asthmatic
      bronchitis, diabetes mellitus, anemia. Adequate stable anesthesia was achieved in
      reduced dosage of conventional anesthesiological agents.

PMID- 10081394
TI  - [Restoring the tracheal lumen in the scar closure of its upper part by lysing of
      the cartilaginous frame].
AB  - Reestablishment of the tracheal lumen in its scarring is described. External
      approach is used to dissect scars in the trachea. The laryngotracheal prosthesis
      (water-filled cylindric latex balloon fixed to the tracheotomy tube) is placed in
      the lumen until epithelized (at least for 4 months). The plates 10 mm in size are
      cut off the rib auto-cartilage, formed as a ring and fixed on the teflon coils
      which are inserted in the tissues of the anterior abdominal wall for a month.
      Thus, the plates acquire a stable semi-ring form. Without removal of the
      laryngotracheal prosthesis, the semi-rings are implanted into the tissues around
      the upper tracheal part. The laryngotracheal prosthesis is removed 1 month after
      this. The trachea was reconstructed in 3 patients by this procedure. All of them
      resumed normal natural breathing.

PMID- 10081395
TI  - [Surgical treatment of bilateral laryngeal paralysis by lateral fixation of the
      vocal fold].
AB  - Lateral fixation of the vocal fold (modified Ejnell's operation) was made in 17
      patients with bilateral laryngeal paralyses. Such operation is simple to perform,
      low-traumatic, safe and effective.

PMID- 10081396
TI  - [Congenital juvenile respiratory papillomatosis of the larynx].
AB  - The data obtained by foreign and national investigators on pathogenesis of
      congenital juvenile papillomatosis allow to confirm the existence of a congenital
      form of juvenile respiratory papillomatosis of the larynx.

PMID- 10081397
TI  - [Long-term results of combined laryngeal resections in stage III-IV cancer using
      endoprostheses made of different polymeric materials].
AB  - The analysis of effectiveness of combined vertical and horizontal laryngeal
      resections with application of endoprostheses for cancer stage III-IV has shown
      that the biocompatible polymeric endoprostheses based on vinylpyrrolidone and
      alkyl methacrylate are superior to endoprostheses made of medical silicone by
      frequency of operative wound healing by first intention, by feasibility of
      tracheostoma one-stage permanent suturing at operation and early decannulation,
      by the degree of correction of external respiration dysfunction and blood gas
      composition. Long-term therapeutic results of application of biocompatible
      polymeric endoprosthesis are similar to those in using endoprosthesis made of
      biologically intact material--medical silicone.

PMID- 10081398
TI  - [Bronchopulmonary complications in patients with laryngeal cancer: features of
      preoperative care].
AB  - 582 case records of patients with cancer of the larynx have been examined for
      associated bronchopulmonary disease. Bronchopulmonary complications were
      registered in 90.7, 38.9% of patients with tracheostoma and without it,
      respectively, in 21.3% of control patients. The original trial included 80
      patients of the study group and 50 control patients. The study of blood gases and
      acid-base balance, external respiration function has revealed compensated
      acidosis in both groups (more pronounced in the study group before operation),
      respiratory distress in the study group. The removal of the tumor resulted in
      improvement of the external respiration and normalization of blood gases and acid
      base balance. A complex of diagnostic, therapeutic and prophylactic measures is
      proposed against bronchopulmonary complications in laryngeal cancer.

PMID- 10081399
TI  - [Use of x-ray endovascular occlusion in combined treatment of juvenile
      angiofibroma of the skull base in children].
AB  - Of a total of 103 patients with juvenile angiofibroma of the base of the skull
      surgical treatment was given to 98 children. 10 operations were performed after
      preoperative roentgeno-endovascular occlusion (REO) of the tumor afferent
      vessels. Such occlusion in the region of a maxillaris was a sufficient measure to
      warrant a 2-fold reduction in the intraoperative blood loss and was achieved with
      hydrogel spheres and cylinders 0.4-0.6 mm in diameter. 4 days are an optimal time
      for operative intervention after the REO. The nasomaxillary approach was used in
      most cases preceded by diagnostic carotid angiography in the frontal and lateral
      views. No complications arose due either to the angiography or REO. The latter
      was found beneficial when performed prior to surgical intervention for juvenile
      angiofibroma of the base of the skull.

PMID- 10081400
TI  - [Rhinoliths].
AB  - 16 cases of rhinoliths were registered in the ENT clinic for 12 years. The
      patients were aged 12 to 63 years (4 males and 12 females). Solitary rhinoliths
      occurred in 14, multiple ones in 2 patients. Four groups of rhinoliths are
      distinguished basing on the time of the rhinolith occurrence in the nose after
      occasional introduction of the foreign body, rhinolith weight, size, negative
      effects on the adjacent tissues and organs.

PMID- 10081401
TI  - [Methods of drainage and tamponment in otorhinolaryngologic practice].
AB  - Current methods of drainage and tamponment are reviewed. The drainage is made
      more often with the use of gauze and glove rubber. To drain deep wound channels,
      in mediastinitis for instance, a silicone double tube is employed. To prevent
      repeat bleeding, it is better to remove the tampon of gauze turundas step-by
      step, after saturation with wound discharge and blood. Long-standing nasal
      tampons may cause complications. In these cases prophylactic doses of antibiotics
      are recommended. The cigar tampon is useful for prevention of nasopharyngeal
      bedsores in patients with posterior tamponment. Such tampons with lateral holes
      are also convenient for drainage of cerebral abscesses.

PMID- 10081402
TI  - [Experience in the use of eucalymine in acute inflammatory ENT diseases in
      children].
AB  - Eucalyptus-based drug eucalymine made in Russia has been tried in children with
      acute maxillary sinusitis, exacerbation of chronic purulent maxillary sinusitis
      and peritonsillar abscess. The findings indicate a good antiinflammatory effect
      of eucalymine which can be used as a treatment of choice in children with ENT
      diseases.

PMID- 10081403
TI  - [A rare foreign body in the larynx and trachea].

PMID- 10081404
TI  - [Multiple otogenic abscesses of the cerebellum and brain].

PMID- 10081405
TI  - [Removal of the stapes from the tympanic cavity while cleaning the ear with
      cotton wool].

PMID- 10081406
TI  - [Heliogeophysical factors and ENT diseases].

PMID- 10081407
TI  - [Otoacoustic emission: the investigation of the normal parameters].

PMID- 10081408
TI  - [Otological effects of the impulse noise].
AB  - Literature data are reviewed on otoacoustic emission which is not widely known in
      Russia as a method of assessing acoustic function. Normal parameters of
      otoacoustic emission obtained in subjects with normal hearing are provided.

PMID- 10081409
TI  - [The status of acoustic and vestibular function among the workers of phosphorus
      industry].
AB  - Hearing of 502 subjects occupationally exposed to noise was evaluated using
      threshold, suprathreshold and speech audiometry. 240 of them worked in conditions
      of impulse noise, 262 were exposed to permanent noise. Impulse noise proved more
      harmful for the acoustic analyzer. More unfavourable effect of impulse noise vs
      permanent one should be accounted for when conducting prophylactic examinations
      of subjects exposed to impulse noise.

PMID- 10081410
TI  - [Chronic kidney failure and hearing disorders].
AB  - Long-term occupational exposure to phosphorus compounds cause cochleovestibular
      disorders which, at the stage of marked intoxication, manifest with symptoms of
      cochlear neuritis with signs of vestibular dysfunction. This affection, among
      other manifestations of chronic occupational phosphorus intoxication, should be
      taken in consideration by the experts assessing working ability of employees in
      contact with phosphorus compounds.

PMID- 10081411
TI  - [Age-specific structural features of the nasal septum in children].
AB  - Hearing was studied in 20 and 34 patients with subclinical and initial renal
      failure (RF), respectively. RF was secondary to chronic glomerulonephritis,
      chronic pyelonephritis, renal polycystosis (29, 24 and 1 patients, respectively).
      Hearing function was assessed at tonal threshold, suprathreshold and speech
      audiometry, ultrasound investigations. It was found that one third of the
      patients had bilateral symmetric hearing disorder of neurosensory hypoacusis
      type. The affection was not severe but involved both peripheral and central
      compartments of the acoustic analyzer. High-frequency sound sensitivity suffered
      most of all. There was a rise in hearing thresholds by air and bone conductivity
      at frequencies 12-18 kHz. This rise was the only marker of affected acoustic
      analyzer in 39% of the examinees. 12% of the patients demonstrated elevated
      hearing thresholds combined with elevated ultrasound thresholds, low differential
      threshold of sound intensity and abnormal threshold adaptation.

PMID- 10081412
TI  - [Clinical and morphological aspects of benign tumor-like growths in the vocal
      cords].
AB  - The structure of the nasal septum was studied on 34 samples obtained from dead
      bodies of children aged 3 to 14. The septums were removed from the skull cavity.
      The morphometric studies consisted of measurements of the anteroposerior,
      superior-inferior, septum and its area, as well as composite anatomical
      structures. It is shown that the size and area of the septum and its anatomical
      structures undergo age-specific changes which are not regular. The data should be
      accounted for in correction of nasal septum structural defects in children of
      different age.

PMID- 10081413
TI  - [On the therapeutic methods of facial bone injuries].
AB  - The authors present clinicomorphological characteristics of 2293 patients with
      benign neoplasms of the vocal cords. Nodules predominated in females, contact
      granulomas in males. Histological and histochemical evidence indicates that polyp
      like new growths of the vocal cords known as fibromas, angiofibromas and nodules
      are not tumors. They are rather edematous, edematous-fibrous and angiomatous
      polyps arising as a reaction of vocal cords mucosa to phonatory trauma or
      chemical irritants.

PMID- 10081414
TI  - [Emergency diseases of the larynx and pharynx (comparative statistics)].
AB  - 473 patients with face skeleton traumas were treated. Bones of the nose, nose and
      paranasal sinuses, paranasal sinuses were injured in 83.7, 5.2 and 3.5% of the
      patients, respectively. Combined traumas of the nose, nasal sinuses, zygomatic
      bone and the orbit were observed in 7.6% of the examinees. Nasal fractures with
      displacement were encountered in 62%, without displacement in 38% of the
      patients. In most of the cases reposition of the nasal bones was conducted
      endonasally early after the trauma, late reposition was made 5-days after the
      trauma. In fractures of the zygomatic bone with displacement and of the orbit,
      reposition of the bone was carried out either through the maxillary bone or
      externally with Limberg's hook. In the fractures of the inferior orbital wall,
      revision of the bone wall was made via the external cut along the orbital
      margins. Multiple small fragments were removed, the plate of high molecular
      polyethylene 2 x 2.5 cm in size was inserted subperiosteally. After the revision,
      the maxillary sinus was tamponed with iodoform tampon for fixation. The tampon
      was removed in 9 days maximum. Participation of the dentist and ophthalmologist
      in surgical treatment of combined traumas of the face skeleton bones improves the
      operation outcome, reduces the number of complications, cosmetic defects and
      persistent functional disorders.

PMID- 10081415
TI  - [Treatment-related aldosterone changes in cancer of the middle part of the
      larynx].
AB  - Radioimmunoassay was employed to investigate time course changes in blood serum
      aldosteron in 28 patients with cancer of the middle laryngeal part before and
      after radiation treatment as well as after radiation treatment followed by
      surgical intervention. Initial values of aldosteron were low evidencing impaired
      mineral-corticoid activity of the adrenal cortex. Aldosteron returned to normal
      after effective radiotherapy at early tumor stage and after radical surgical
      treatment at later cancer stages. Hormonal unbalance provides more significant
      information on tumor involvement of the larynx and is a good indicator of the
      treatment efficiency.

PMID- 10081416
TI  - [Middle mass molecules as an indicator of intoxication in the purulent
      inflammatory ENT diseases].
AB  - Middle-mass molecules (MMM) were measured in ENT patients hospitalized urgently
      for purulent sinusitis with orbital complications, mastoiditis, parapharyngitis,
      paratonsillar abscesses, complicated furuncles of the nose and upper lip,
      abscessing epiglottitis, etc. MMM amount, as an indicator of endogenic
      intoxication, were studied in 150 ENT patients aged 15 to 63 years. With the
      number of MMM it was found feasible to follow up and compare endogenic
      intoxication and thus control and correct of the treatment efficacy.

PMID- 10081418
TI  - [Endoscopic application of surgical lasers in persistent obstructions in
      laryngopharynx, larynx and trachea in children].
AB  - CO2, YAG-Nd and copper lasers were applied for elimination of persistent
      obstruction of the laryngopharynx, larynx and trachea in 331 patients aged 23
      days to 15 years. Scar stenosis, vascular tumors, cysts, nonspecific granulemas
      were diagnosed in 271, 29, 8 and 23 patients, respectively. Current and newly
      developed techniques reducing thermal damage to the adjacent to laser-exposed
      tissues and principles of laser treatment choice for different obstructions are
      analysed.

PMID- 10081419
TI  - [Current methods of plastic surgery of the floor of the auricle].
AB  - 138 patients with subtotal congenital defects of the floor of the auricle (FA)
      were operated in childhood or adolescence using a modified method of making the
      frame from the costal cartilage. 3-4 staged FA plastic reconstruction takes about
      a year.

PMID- 10081420
TI  - [On the clinical significance of the trephined cavity status in patients with
      radical surgery of the middle ear].
AB  - 303 ears were examined otomicroscopically in 267 patients who had undergone
      radical operation on the middle ear (RO). Local and general symptoms in patients
      after RO were defined as "the operated ear disease". Otomicroscopic picture of
      pathomorphological changes in the trepanation cavity is provided. It is necessary
      to account for these changes in planning reconstructive surgery.

PMID- 10081421
TI  - [The use of tranexamic acid as an anesthetic component in ENT surgeries in
      patients with high surgical-anesthetic risk and in hemorrhagic shock intensive
      therapy].
AB  - Experimental and clinical trials have shown that anesthesia and intensive therapy
      of shock incorporating tranexamic acid enhance analgesia, hyporeflexia, thus
      ensuring stable, adequate anesthesia which is safe under reduced doses of
      standard anesthesiological modalities. Application of tranexamic acid provided
      more favourable course of postanesthesiological and postoperative periods,
      decreased the number of complications and lethal outcomes compared to standard
      anesthesia.

PMID- 10081422
TI  - [Strepsils plus in the treatment of pharyngeal inflammation].

PMID- 10081423
TI  - [Unilateral tonsillectomy complicated by glossopharyngeal nerve neuralgia and
      late hemorrhage from the tonsillar segment].

PMID- 10081424
TI  - [An acute phlegmonous epiglottitis in an adult].

PMID- 10081425
TI  - [Acute epiglottitis in children].

PMID- 10081426
TI  - [Sleep apnea syndrome in a 3-year-old child].

PMID- 10081427
TI  - [Benign tumors of the nasal cavity, paranasal sinuses and nasopharynx in
      childhood].

PMID- 10081428
TI  - Tuning in to manic depression.

PMID- 10081429
TI  - Exercise: gain without pain.

PMID- 10081430
TI  - The fuss over fiber.

PMID- 10081431
TI  - Can diet prevent cancer?

PMID- 10081432
TI  - Home monitoring for warfarin users.

PMID- 10081433
TI  - Improving radiation therapy for prostate cancer.

PMID- 10081434
TI  - Alcohol's effects on breast cancer in women.

PMID- 10081435
TI  - Alcohol's effects on prostate enlargement in men.

PMID- 10081436
TI  - Celiac disease underdiagnosed?

PMID- 10081437
TI  - Pravastatin for reducing stroke risk.

PMID- 10081438
TI  - When two drugs are better than one.

PMID- 10081439
TI  - Do you need this heart disease test?

PMID- 10081440
TI  - A decade of medical triumphs.

PMID- 10081441
TI  - Colorectal cancer: when to start screening.

PMID- 10081442
TI  - I urinate at least three times a night. Is this normal for older women?

PMID- 10081443
TI  - Are Pap smears necessary after menopause?

PMID- 10081444
TI  - Recruiting. Bounced back.

PMID- 10081445
TI  - Staffing. Docs on demand.

PMID- 10081446
TI  - Niches. Holy-stic health.

PMID- 10081447
TI  - Emergent trends. 7 ways to care.

PMID- 10081448
TI  - Should nurses join unions?

PMID- 10081449
TI  - Interiors. Doctored design.

PMID- 10081450
TI  - High on health care.

PMID- 10081451
TI  - Treatment. The fix for a fixation.

PMID- 10081452
TI  - Master class. Interview by Chris Serb.

PMID- 10081453
TI  - Play to win. No matter what your business, creativity can make it better.

PMID- 10081454
TI  - Health care's 100 most wired.
AB  - They're wired all right, and America's 100 most techno-savvy hospitals and health
      systems share one more thing: a commitment to using technology to link with
      employees, patients, suppliers, and insurers. "We want to be a health care travel
      agency for our community," says one chief information officer. "And we see
      Internet technology as a key."

PMID- 10081455
TI  - Business unusual. Allina, winner of the 1998 McGaw Prize, is pioneering a new
      treatment: boosting health at the grassroots.

PMID- 10081456
TI  - Out there care. There's strength in strange: Lifeguard, the HMO that doesn't act
      like one, boasts top ratings from consumers, fat profits, and zero debt.

PMID- 10081457
TI  - An interview with Jim Clark. Interview by Michael Menduno.

PMID- 10081458
TI  - Strategic surgery.

PMID- 10081459
TI  - Fun runs & faux pas.

PMID- 10081460
TI  - Canada's drug problem: time to get serious.

PMID- 10081461
TI  - Watch out for drug-drug interactions, too!

PMID- 10081462
TI  - Improving communication skills.

PMID- 10081463
TI  - Improving communication skills.

PMID- 10081464
TI  - The cost of obesity in Canada.
AB  - BACKGROUND: Almost one-third of adult Canadians are at increased risk of
      disability, disease and premature death because of being obese. In order to
      allocate limited health care resources rationally, it is necessary to elucidate
      the economic burden of obesity. OBJECTIVE: To estimate the direct costs related
      to the treatment of and research into obesity in Canada in 1997. METHODS: The
      prevalence of obesity (body mass index of 27 or greater) in Canada was determined
      using data from the National Population Health Survey, 1994-1995. Ten
      comorbidities of obesity were identified from the medical literature. A
      population attributable fraction (PAF) was calculated for each comorbidity with
      data from large cohort studies to determine the extent to which each comorbidity
      and its management costs were attributable to obesity. The direct cost of each
      comorbidity was determined using data from the Canadian Institute of Health
      Information (for direct expenditure categories) and from Health Canada (for the
      proportion of expenditure category attributable to the comorbidity). This
      prevalence-based approach identified the direct costs of hospital care, physician
      services, services of other health professionals, drugs, other health care and
      health research. For each comorbidity, the cost attributable to obesity was
      determined by multiplying the PAF by the total direct cost of the comorbidity.
      The overall impact of obesity was estimated as the sum of the PAF-weighted costs
      of treating the comorbidities. A sensitivity analysis was completed on both the
      estimated costs and the PAFs. RESULTS: The total direct cost of obesity in Canada
      in 1997 was estimated to be over $1.8 billion. This corresponded to 2.4% of the
      total health care expenditures for all diseases in Canada in 1997. The
      sensitivity analysis revealed that the total cost could be as high as $3.5
      billion or as low as $829.4 million; this corresponded to 4.6% and 1.1%
      respectively of the total health care expenditures in 1997. When the
      contributions of the comorbidities to the total cost were considered, the 3
      largest contributors were hypertension ($656.6 million), type 2 diabetes mellitus
      ($423.2 million) and coronary artery disease ($346.0 million). INTERPRETATION: A
      considerable proportion of health care dollars is devoted to the treatment and
      management of obesity-related comorbidities in Canada. Further research into the
      therapeutic benefits and cost-effectiveness of management strategies for obesity
      is required. It is anticipated that the prevention and treatment of obesity will
      have major positive effects on the overall cost of health care.

PMID- 10081465
TI  - Candidemia at selected Canadian sites: results from the Fungal Disease Registry,
      1992-1994. Fungal Disease Registry of the Canadian Infectious Disease Society.
AB  - BACKGROUND: Candida species are important bloodstream pathogens that are being
      isolated with increasing frequency. Despite the availability of effective
      antifungal therapy, the mortality rate associated with Candida infection remains
      high. With the objective of describing the epidemiology of candidemia, the
      Canadian Infectious Disease Society conducted a study of candidemia in Canada.
      METHODS: Fourteen medical centres across Canada identified all patients with
      candidemia from March 1992 to February 1994 through blood culture surveillance
      for Candida spp. Patient-related data for invasive fungal infection were compiled
      retrospectively by chart review using a standardized data-recording form
      developed for the Fungal Disease Registry of the Canadian Infectious Disease
      Society. Cases of Candidemia were studied in relation to underlying medical
      conditions, predisposing factors, concurrent infection, antimicrobial agents,
      antifungal treatment and deaths. RESULTS: In total, 415 cases of candidemia were
      identified, 48 (11.6%) in children and 367 (88.4%) in adults. The causative
      pathogens were C. albicans in 286 cases (68.9%), C. parapsilosis in 43 (10.4%),
      C. glabrata in 34 (8.2%), C. tropicalis in 27 (6.5%) and other Candida species in
      18 (4.3%); polymicrobial candidemia occurred in 7 cases (1.7%). The overall
      mortality rate was 46%, and the rate of deaths clinically related to candidemia
      was 19%. However, only 13 (27%) of the children died. A univariate analysis
      indicated that significant risk factors for death were age greater than 60 years,
      therapy for concomitant bacterial infection, stay in an intensive care unit,
      concurrent malignant disease, cytotoxic chemotherapy and granulocytopenia,
      although only age and stay in an intensive care unit emerged as significant risk
      factors in the multivariate analysis. After adjustment for other predictors of
      death, only infection with C. parapsilosis was associated with a lower mortality
      rate than infection with C. albicans. Treatment was given in 352 (84.8%) of
      cases. Amphotericin B was the preferred agent in 244 cases (69.3% of those
      treated); fluconazole was used in 101 cases (28.7%) and ketoconazole in 5 cases
      (1.4%). INTERPRETATION: Candidemia in Canada is caused predominantly by C.
      albicans. The mortality rate associated with candidemia is high, but it varies
      with the species of Candida and is lower in children than in adults. Age greater
      than 60 years and stay in an intensive care unit were the most significant risk
      factors for overall mortality.

PMID- 10081466
TI  - Call for action: preventing and managing the expansive and expensive obesity
      epidemic.

PMID- 10081467
TI  - Science, sex and semantics: the firing of George Lundberg.

PMID- 10081469
TI  - Prostate cancer: 11. Alternative approaches and the future of treatment.

PMID- 10081468
TI  - Periodic health examination, 1999 update: 1. Detection, prevention and treatment
      of obesity. Canadian Task Force on Preventive Health Care.
AB  - OBJECTIVES: (1) To evaluate the evidence relating to the effectiveness of methods
      to prevent and treat obesity, and (2) to provide recommendations for the
      prevention and treatment of obesity in adults aged 18 to 65 years and for the
      measurement of the body mass index (BMI) as part of a periodic health
      examination. OPTIONS: In adults with obesity (BMI greater than 27) management
      options include weight reduction, prevention of further weight gain or no
      intervention. OUTCOMES: The long-term (more than 2 years) effectiveness of (a)
      methods to prevent obesity and (b) methods to treat obesity. EVIDENCE: MEDLINE
      was searched for articles published from 1966 to April 1998 that related to the
      prevention and treatment of obesity; additional articles were identified from the
      bibliographies of review articles and the listings of Current Contents. Selection
      criteria were used to limit the analysis to prospective studies with at least 2
      years' follow-up. BENEFITS, HARM AND COSTS: Health benefits of weight reduction
      were evaluated in terms of alleviation of symptoms, improved management of
      obesity-related diseases and a reduction in major clinical outcomes. The health
      risk of weight-reduction methods were briefly evaluated in terms of increased
      mortality and morbidity. VALUES: The recommendations of this report reflect the
      commitment of the Canadian Task Force on Preventive Health Care to provide a
      structured, evidence-based appraisal of whether a manoeuvre should be part of a
      periodic health examination. RECOMMENDATIONS: (1) PREVENTION: There is
      insufficient evidence to recommend in favour of or against community-based
      obesity prevention programs; however, because of considerable health risks
      associated with obesity and the limited long-term effectiveness of weight
      reduction methods, the prevention of obesity should be a high priority for health
      care providers (grade C recommendation). (2) TREATMENT: (a) For obese adults
      without obesity-related diseases, there is insufficient evidence to recommend in
      favour of or against weight-reduction therapy because of a lack of evidence
      supporting the long-term effectiveness of weight-reduction methods (grade C
      recommendation); (b) for obese adults with obesity-related diseases (e.g.,
      diabetes mellitus, hypertension), weight reduction is recommended because it can
      alleviate symptoms and reduce drug therapy requirements, at least in the short
      term (grade B recommendation). (3) Detection: (a) for people without obesity
      related diseases, there is insufficient evidence to recommend the inclusion or
      exclusion of BMI measurement as part of a periodic health examination, and
      therefore BMI measurement is left to the discretion of individual health care
      providers (grade C recommendation); (b) for people with obesity-related diseases,
      BMI measurement is recommended because weight reduction should be considered with
      a BMI of more than 27 (grade B recommendation). VALIDATION: The findings of this
      analysis were reviewed through an iterative process by the members of the
      Canadian Task Force on Preventive Health Care. SPONSORS: The Canadian Task Force
      on Preventive Health Care is funded through a partnership between the Provincial
      and Territorial Ministries of Health and Health Canada.

PMID- 10081470
TI  - Bacterial contamination of blood components: Is it in the bag?

PMID- 10081471
TI  - Storage of cord blood attracts private-sector interest.
AB  - Storage of cord blood from their babies can cost parents several hundred dollars,
      and some private companies are already offering the service. Janis Hass reports
      that some Canadian specialists question the value of the banks.

PMID- 10081472
TI  - Solving stubborn-wound problem could save millions, team says.
AB  - Why do some wounds refuse to heal? A team in London, Ont., is attempting to
      determine the cellular and molecular clues that could lead to better treatment of
      recalcitrant wounds.

PMID- 10081473
TI  - Medical simulation is wave of the future, U of O doctors say.

PMID- 10081475
TI  - [Truth in medicine. 6th Fall Meeting of the corporate members of the German
      Society for Internal Medicine].

PMID- 10081474
TI  - [HIV therapy in women begins earlier].

PMID- 10081476
TI  - [Occupational exposure in the hospital to laughing gas and the new inhalation
      anesthetics desflurane and sevoflurane].
AB  - BACKGROUND AND OBJECTIVE: There have been few studies of the occupational
      exposure of the new volatile anaesthetic agents desflurane and sevoflurane.
      Because a health risk through long-term exposure to these inhalants cannot as yet
      be definitely excluded, we undertook to measure the concentrations of these three
      anaesthetics in different parts of the Frankfurt University Medical Centre.
      Considering the results the relevance of exposure for surgical and anaesthesia
      personnel, possible consequences due to laws and possibilities of improvement
      were shown. METHODS: The concentration of the three anaesthetics was measured
      during and after 345 procedures under general anaesthesia, using photoacoustic
      infra-red-spectrometry every 90 sec in the breathing zone of the same operating
      room personnel or in the recovery room and the intensive care unit. RESULTS:
      Exposure of personnel in the air-conditioned operating rooms was very low, but in
      those rooms that were not or inadequately air conditioned was a times very high.
      The level of the concentrations was also significantly related to the anaesthesia
      system and the distance of the exposed person to the patient. The concentration
      of nitrous oxide was below the maximal working-place concentration (MWC) of 100
      ppm, but it exceeded the threshold concentration of 0.1 MAC, as laid down in the
      "Maternal Protection Law" in the surgical intensive care unit and the recovery
      room. There are no limiting concentrations for desflurane and sevoflurane yet but
      their concentrations were clearly below the MWC laid down for isoflurane and
      enflurane. CONCLUSION: In principle the use of inhalation anaesthetics can be
      considered to be without occupational health risk under the present legally
      defined standards of air-conditioning and the requirements of a modern
      occupational protection law. Because of the increased concentrations in the
      recovery room and intensive care unit pregnant and breast-feeding women should
      not work in these areas.

PMID- 10081477
TI  - [Pyoderma gangrenosum and portal vein thrombosis in a 33-year-old female
      patient].
AB  - HISTORY AND CLINICAL FINDINGS: The diagnosis of pyoderma gangraenosum (PG) was
      made in a 33-year-old woman with ulcerative (palm-sized) skin changes and pain of
      the lower leg that had developed over two weeks and was accompanied by fever (39
      degrees C). Treatment with prednisolone and azathioprine was initiated. As soon
      as the medication was reduced new skin changes developed. Two months after onset
      of the illness she had to be hospitalized because of fever, epigastric pain on
      pressure and deteriorating general condition. Physical examination provided no
      significant further information. LABORATORY RESULTS: The differential count
      demonstrated leucocytosis (15.5 Gpt/l) with a marked monocytosis (25%) as well as
      anaemia (haemoglobin concentration 5.2 mmol/l). C-reactive protein was elevated
      (120.20 mg/l). Thromboplastin time was 60%, D-dimer 1000 micrograms/l, thrombin
      antithrombin-III complex 9.7 micrograms/l. ADDITIONAL INVESTIGATIONS: Sonography
      and computed tomography of the upper abdomen revealed splenomegaly, ascites,
      thrombosis of the portal, splenic and superior mesenteric veins. Bone marrow
      puncture showed marked increase in blasts (14%) and monocytes (10%). TREATMENT
      AND COURSE: The findings indicated chronic myelomonocytic leukaemia with PG and
      the described venous thromboses. The cutaneous changes completely receded on
      administration of hydroxyurea (1.0 g/d). Other causes of the skin eruption were
      excluded. Phenprocoumon (INR between 2 and 3) was given in treatment of the
      thromboses. CONCLUSION: When PG is diagnosed, intensive search for an underlying
      cause must be undertaken, because of its frequent association with serious
      systemic disease. Only early specific treatment will improve the skin condition.

PMID- 10081478
TI  - [The duodenojejunal flexure--a gap in the routine diagnosis of gastrointestinal
      bleeding].
AB  - HISTORY AND ADMISSION FINDINGS: Because of tarry stools a 64-year-old woman had
      two years previously undergone oesophagogastroduodenoscopy (OGD), coloscopy and
      examination of the small intestine (according to Sellink) without significant
      findings. She was again hospitalized because of anemia (6.1 g/dl). Physical
      examination was unremarkable. INVESTIGATIONS: After unremarkable OGD (as far as
      the descending part of the duodenum) and coloscopy, hypotonic duodenography
      revealed a tumor in the region of the duodenojejunal flexure. TREATMENT AND
      COURSE: The tumor, histologically a leiomyoma, was resected. CONCLUSION: OGD,
      coloscopy and small intestinal radiography may fall to identify the source of
      bleeding because of a diagnostic gap in the region of the duodenojejunal flexure.
      In this case hypotonic duodenography should be performed, if enteroscopy is not
      available.

PMID- 10081479
TI  - [Sildenafil].

PMID- 10081480
TI  - [Value of spiral computer tomography for the diagnosis of acute pulmonary
      embolism].

PMID- 10081481
TI  - [Virology, epidemiology and diagnosis of herpes genitalis].

PMID- 10081482
TI  - [Similarities of chronic fatigue syndrome, fibromyalgia and multiple chemical
      sensitivity].

PMID- 10081483
TI  - Mapping and sequencing of the human genome.

PMID- 10081484
TI  - A long-term follow-up study on risk factors for hepatocellular carcinoma among
      Japanese patients with liver cirrhosis.
AB  - To identify virological parameters (serostatus of hepatitis B surface antigen
      [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA
      titer) and other clinico-biological and lifestyle variables that may influence or
      predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we
      followed 100 cirrhotic patients without HCC, who visited Kyushu University
      Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%;
      average follow-up period: 5.3 years). After elimination of 4 patients who
      developed HCC or were censored within the initial 6 months, 37 (39%) out of 96
      patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti
      HCV(+) HBsAg(-) patients demonstrated significantly elevated HCC risk (adjusted
      hazard ratio [HR] = 5.85, 95% confidence interval [CI] 1.65-20.67). Genotype 1
      HCV infection was not associated with increased risk compared with genotype 2 (HR
      = 0.64, 95% CI 0.21-1.99). For genotype 1 HCV infection, patients with HCV-RNA
      levels < 1 Meq/ml tended to present lower risk than patients with > or = 1 Meq/ml
      (P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher
      serum aminotransferase and alpha-fetoprotein were also found to be strong
      predictors. Overall, drinking and smoking habits were not associated with
      significantly elevated risk. Among virological parameters, anti-HCV positivity
      and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis
      in our clinical setting.

PMID- 10081485
TI  - The implication of anthracosis in the development of pulmonary adenocarcinoma.
AB  - The relationship between anthracosis, which is the deposition of black dust
      matter in the lung parenchyma, and the development of pulmonary adenocarcinoma
      has not been fully characterized. In order to clarify whether background black
      dust matter deposition could be implicated in the development of pulmonary
      adenocarcinoma, we measured the level of anthracosis at autopsy in 47 patients
      who had died of pulmonary adenocarcinoma. Both lungs of all 47 cadavers were
      examined. Twenty-micrometer sections were cut from formalin-fixed, paraffin
      embedded blocks of the largest cut surface of each lung. Black dust matter was
      extracted from the sections and blotted onto a nitrocellulose membrane. The
      density of the blotted black dust matter was then analyzed using an imaging
      densitometer. There were no significant differences in the density of black dust
      matter deposition between lungs affected by pulmonary adenocarcinoma and control
      lungs. However, well differentiated adenocarcinomas tended to develop more
      frequently than poorly differentiated ones in lungs showing less deposition. We
      found a very strong correlation between the degree of black dust matter
      deposition and smoking history. Patients with severe anthracosis tended to have a
      poorer prognosis than those with mild anthracosis.

PMID- 10081486
TI  - Growth inhibition, enhancement of intercellular adhesion, and increased
      expression of carcinoembryonic antigen by overexpression of phosphoinositides
      specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line.
AB  - By using a retrovirus-derived system we generated derivatives of the human colon
      adenocarcinoma cell line LS174T (ATCC CL 188) that stably overexpress a full
      length cDNA encoding the beta 1 isoform of bovine phosphoinositides-specific
      phospholipase C (PI-PLC). This was confirmed by the elevated levels of catalytic
      activity to release phosphoinositides from phosphatidylinositol (PI-PLC) or
      phosphatidylinositol-bis-phosphate (PIP2-PLC), and the enhanced expressions of
      messenger RNA and protein. PI-PLC beta 1 overexpresser clones grew to form cell
      clumps floating in liquid medium, whereas the pMV7-introduced control clones
      displayed morphologic characteristics that were very similar to those of the
      parent LS174T cell line. Three individual PI-PLC beta 1 overexpresser cell lines
      displayed increased doubling time (18.0 h, 21.5 h, and 23.8 h) when compared with
      4 individual pMV7-introduced control cell lines (13.1 h, 10.7 h, 12.9 h, and 9.3
      h). Anchorage-independent growth ability in soft agar medium was dramatically
      suppressed by overexpression of PLC beta 1, and the ability of PLC-overproducer
      clones to form aggregates when cultured in liquid medium was dramatically
      enhanced when compared with that of pMV7-introduced control clones.
      Tumorigenicity of PLC beta 1-overproducers was much weaker than that of vector
      transduced control clones. The spontaneous release of carcinoembryonic antigen
      from PLC beta 1-overproducer clones was much higher than that from pMV7 control
      clones. The ability of PLC beta 1-overproducer clones to form aggregates during
      suspension culture was much stronger than that of the control clones. These
      results provide the first evidence that elevated levels of endogenous PI-PLC beta
      1 suppress tumor cell growth, but enhance the ability to form cell aggregates and
      to release carcinoembryonic antigen, an intercellular adhesion molecule.

PMID- 10081487
TI  - Expression of mucin-associated sulfo-Lea carbohydrate epitopes on human colon
      carcinoma cells.
AB  - The level of sulfo-Lea (SO3-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc) epitope
      recognized by monoclonal antibody (mAb) 91.9H in hepatic metastasis of colon
      carcinoma is known to be lower than at the primary sites. We examined 19 human
      colon carcinoma cell lines for their production of this epitope. Sixteen cell
      lines were found to produce high M(r) components that metabolically incorporated
      [35S]sulfate and were resistant to heparitinase I and chondroitinase ABC, and 8
      of them were reactive with mAb 91.9H as shown by western blotting analysis. These
      were all of the 4 cell lines derived from well differentiated primary tumors
      (HCCP-2998, LS174T, GEO, and CBS), 2 of 10 cell lines (DLD-1 and HCT116) from
      moderately to poorly differentiated primary tumors, and 2 of 5 cell lines (SW480
      and HCC-M1544) from metastases. Incubation of LS174T cells with benzyl-N-acetyl
      alpha-D-galactosaminide abrogated the incorporation of [35S]sulfate and the
      reactivity of mAb 91.9H with high M(r) components in the cell lysates. Sodium
      chlorate, which inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate,
      also inhibited the [35S]sulfate incorporation and reactivity with mAb 91.9H.
      These treatments did not change the incorporation of [14C]threonine into high
      M(r) components. These results indicated that sulfo-Lea epitopes were expressed
      on O-linked carbohydrate chains in sulfomucins. Immunohistochemical studies of
      tumor tissues in nude mice indicated that sulfo-Lea was expressed at the site of
      orthotopic transplantation in the cecum. The expression appeared to be suppressed
      in liver metastatic foci in nude mice.

PMID- 10081488
TI  - Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver
      tumors and its relevance to clinical behavior.
AB  - Advanced neuroblastoma and malignant liver tumor are representative childhood
      cancers for which combined chemotherapy including cisplatin and doxorubicin is
      routinely performed. The prognosis of patients with tumors which develop multiple
      drug resistance (MDR) is unfavorable. To elucidate the role of multidrug
      resistance-associated protein (MRP) and canalicular multispecific organic anion
      transporter (cMOAT) in the clinical behavior of the tumors, we examined 42
      neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT
      by quantitative RNA-polymerase chain reaction (PCR). The amplification and
      expression of N-myc oncogene in the neuroblastomas were also investigated. We
      found a close association between MRP and N-myc expression in each neuroblastoma
      sample but no significant relationship between MRP expression and the patients'
      outcome. The forced expression of N-myc failed to enhance the expression of MRP
      in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the
      neuroblastomas, but was frequently expressed in the malignant liver tumors. The
      expression of MRP and cMOAT in the childhood liver tumors was more common and
      higher, especially in advanced cases with a poor outcome, than that observed in
      normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced
      expression of these genes might be characteristic of childhood malignant liver
      tumors and related to their clinical chemoresistance.

PMID- 10081489
TI  - Mutational analyses of multiple target genes in histologically heterogeneous
      gastric cancer with microsatellite instability.
AB  - It has been recognized that gastric cancer often shows histological heterogeneity
      in a single tumor. Although microsatellite instability (MSI) has been reported in
      gastric cancer, the significance of genomic instability in gastric cancers with
      histological heterogeneity within a single tumor has never been addressed. We
      investigated MSI at 8 microsatellite loci in 40 normal/tumor DNA pairs from 20
      gastric cancers with histological heterogeneity. Six of 20 patients (10 DNAs of
      40 tumor DNAs) had severe MSI in more than 3 loci. Four of the MSI-positive cases
      had frameshift mutations in the poly(A)10 tract of the TGF beta RII gene. This
      mutation was found only in the MSI-positive component in the 2 cases (cases 4 and
      5) in which only 1 component exhibited MSI. The other 4 cases demonstrated
      homozygous or heteroclonal mutations (1 and 2 base deletions) in the poly(A)8
      tract of the hMSH3 gene; no mutation was detected in the poly(C)8 tract of the
      hMSH6 gene in any of the MSI-positive cases. The profile of alterations in
      multiple targets was different between the 2 components in most of the cases
      (5/6). These findings suggest that mismatch repair deficiency in MSI-positive
      tumors causes multiple gene inactivations through frameshift mutations in short
      repetitive sequences in a heterogeneous way within a histologically heterogeneous
      tumor.

PMID- 10081490
TI  - Expression of the SART-1 antigens in uterine cancers.
AB  - We recently reported that the SART-1 gene, encoding the SART-1(259) tumor antigen
      which is recognized by HLA-A26-restricted cytotoxic T lymphocytes (CTLs), is
      expressed in the cytosol of squamous cell carcinomas and adenocarcinomas. The
      present study deals with the expression of SART-1(259) and SART-1(800) antigens
      in uterine cancers. The SART-1(259) antigen was detected in the cytosol fraction
      of 4 of 8 uterine cancer cell lines, 24 of 74 (32%) uterine cancer tissues, 0 of
      7 uterine myomas, and 0 of 5 non-tumorous uterine tissues. The SART-1(800)
      antigen was expressed in the nuclear fraction of all the uterine cancer cell
      lines, 41 of 74 (55%) uterine cancer tissues, 0 of 7 myomas, and 3 of 5 non
      tumorous uterine tissues. The SART-1(259)+ uterine cancer cells were recognized
      by HLA-A24 restricted and SART-1 specific CTLs. Therefore, SART-1(259) antigen
      could be an appropriate vaccine candidate for a relatively large number of
      uterine cancer patients.

PMID- 10081491
TI  - Role of sialylglycoconjugate(s) in the initial phase of metastasis of liver
      metastatic RAW117 lymphoma cells.
AB  - To elucidate the early events of blood-borne metastasis under actual blood flow,
      real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117
      P and liver-metastatic RAW117-H10 cells, was investigated using positron emission
      tomography (PET). Both types of cells accumulated in the liver immediately after
      injection via the portal vein, and were eliminated from the liver time
      dependently. The elimination rate of RAW117-H10 cells, however, was slower than
      that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly
      with hepatic sinusoidal endothelium than the parental cells. This result
      correlated with the metastatic potential of these cells: RAW117-H10 cells
      metastasized in the liver to a greater extent than RAW117-P cells after injection
      via this route. To investigate the role of sialylglycoconjugates in the
      interaction of RAW117-H10 cells with the hepatic endothelium after injection via
      the portal vein, the trafficking of RAW117-H10 cells was examined after the cells
      had been treated with sialidase. The elimination rate of RAW117-H10 cells from
      liver was observed to be greatly accelerated by sialidase treatment. To elucidate
      what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the
      distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of
      RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much
      higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl
      Lewis X did not differ significantly. These findings suggest that some
      sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important
      role in the initial interaction of RAW117-H10 cells with the hepatic endothelium,
      leading to metastasis.

PMID- 10081492
TI  - FK317, a novel substituted dihydrobenzoxazine, exhibits potent antitumor activity
      against human tumor xenografts in nude mice.
AB  - The antitumor effects of FK317, a novel substituted dihydrobenzoxazine, were
      evaluated using human tumor xenografts (small cell lung cancer, non-small cell
      lung cancer, stomach cancer, colon cancer, pancreatic cancer, breast cancer,
      cervical cancer and ovarian cancer). Tumor growth-inhibitory effects and the
      effective dose-range of FK317 were much stronger and broader, respectively, than
      those of reference drugs such as mitomycin C, adriamycin, cisplatin, taxol and
      irinotecan. Furthermore, the body weight decrease and myelosuppression in FK317
      treated mice were less than in the animals given any of the reference drugs. To
      explain this tumor selectivity, the distribution of FK317 was investigated after
      dosing tumor-bearing mice with the 14C-labelled compound. The concentration of
      FK317 in tumor tissues was relatively low, and long tumor retention was not
      observed. However, thin-layer chromatographic separation revealed that the
      radioactivity in the tumor resided mainly in strongly cytotoxic metabolites,
      while that in other tissues resided mainly in non-cytotoxic metabolites. These
      results suggest that FK317 shows strong antitumor activity without side effects,
      and one reason for this is its specific metabolite pattern. FK317 is now
      undergoing phase I clinical trials.

PMID- 10081493
TI  - Anti-cachectic effect of FK317, a novel anti-cancer agent, in colon26 and LX-1
      models in mice.
AB  - The effects of FK317 (11-acetyl-8-carbamoyloxymethyl-4-formyl-6- methoxy-14-oxa
      1,11-diazatetracyclo[7.4.1.0(2, 7). 0(10, 2] tetradeca-2,4,6-trien-9-yl acetate),
      a novel anti-cancer agent, on murine adenocarcinoma colon26- and human lung
      carcinoma LX-1-induced cachexia were investigated in mice. Mice bearing colon26
      or LX-1 s.c. lost weight and became cachectic, associated with tumor growth.
      FK317 and mitomycin C (MMC) inhibited the growth of both tumors. FK317
      ameliorated the weight loss induced by the presence of colon26 or LX-1, while MMC
      enhanced it. An attenuation of the reduction in the weights of epididymal fat,
      gastrocnemius muscle and carcass was observed in FK317-treated tumor-bearing mice
      in both cachexia models, but not in MMC-treated mice. The decreases in the
      circulating levels of triglyceride, glucose and non-esterified fatty acid, which
      were induced by the presence of colon26, was partially inhibited by treatment
      with FK317. Overall, this study revealed that FK317 is a potent anti-cancer drug
      with anti-cachectic activity, suggesting that FK317 has potential utility for the
      treatment of cancer.

PMID- 10081494
TI  - EAT/mcl-1, a member of the bcl-2 related genes, confers resistance to apoptosis
      induced by cis-diammine dichloroplatinum (II) via a p53-independent pathway.
AB  - EAT/mcl-1 showed increased expression during the differentiation of a multipotent
      human embryonic carcinoma cell line, NCR-G3, and of myeloblastic cells "ML-1,"
      and has sequence similarity to Bcl-2. In this present study, we determined
      whether the apoptotic cell death induced by chemotherapeutic agents could be
      inhibited by EAT/mcl-1, as has been found with Bcl-2. Cells transfected with
      EAT/mcl-1 showed higher resistance to cis-diammine dichloroplatinum (II) (CDDP)
      and carboplatin compared with the parental line (10)1 and neomycin-resistance
      gene-transfected clone, (10)1/neo. There was, however, no difference in
      sensitivity to etoposide, N,N-bis-(2-chloroethyl)-N'-(3-hydroxypropyl)
      phosphordiamidic acid cyclic ester monohydrate, adriamycin or other
      chemotherapeutic agents tested. DNA fragmentation of the parental cells following
      treatment with CDDP and carboplatin was observed in a concentration-dependent
      manner. In contrast, cells transfected with EAT/mcl-1 did not show DNA
      fragmentation following treatment with the same concentration of these drugs.
      EAT/mcl-1 was capable of delaying the onset of p53-independent apoptosis,
      although it could not inhibit apoptosis completely. Since CDDP and carboplatin
      damage DNA and then activate c-abl and the JNK/SAPK pathway, EAT/mcl-1 may
      inhibit p53-independent apoptosis through a c-abl/JNK (SAPK)-dependent mechanism.
      EAT/mcl-1 has functional homology to Bcl-2 in that it can enhance cell viability
      under conditions which otherwise cause apoptosis and increase resistance to
      chemotherapeutic agents.

PMID- 10081495
TI  - Effects of sex steroids and growth factors on invasive activity and 5'-deoxy-5
      fluorouridine sensitivity in ovarian adenocarcinoma OMC-3 cells.
AB  - Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth
      factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF
      alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity
      of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration
      along a gradient of substratum-bound fibronectin and invasion into reconstituted
      basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM
      EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect
      on tumor cell migration or invasion. The zymography of tumor conditioned medium
      showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in
      increases of type IV collagenase, stromelysin and urokinase-type plasminogen
      activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase
      (dThdPase) expression of tumor cells and consequently enhanced the
      antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by
      dThdPase. E2 and Prog did not have significant effects on the expression of
      proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells.
      The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory
      action on the motility of tumor cells. These results suggest that EGF and TGF
      alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to
      invade extracellular matrices and their dThdPase expression, both of which are
      associated with the specific action of 5'-dFUrd selectively to kill tumor cells
      with high invasive and metastatic potential.

PMID- 10081496
TI  - Schedule-dependent and -independent antitumor activity of paclitaxel-based
      combination chemotherapy against M-109 murine lung carcinoma in vivo.
AB  - The established antitumor efficacy of paclitaxel against a variety of human
      tumors has led to pre-clinical and clinical studies to develop the paclitaxel
      based combination regimens. We examined in vivo the antitumor activity and
      toxicity of the combination of paclitaxel and each of 8 antitumor agents,
      currently in clinical use, against M-109 murine lung carcinoma implanted
      subcutaneously into male CDF1 mice. Paclitaxel given intravenously at 24
      mg/kg/day on a schedule of consecutive daily injections for 5 days (d1-5) induced
      reproducibly, in 6 experiments, a significant (37-82%) increase in the survival
      time of tumor-bearing mice over saline-treated control mice. Cisplatin at 4 and 2
      mg/kg/day given intravenously on the same treatment schedule showed no
      significant antitumor activity when given alone; however, the combination of
      paclitaxel at 24 mg/kg/day (d1-5) followed by cisplatin at a dose of 2 mg/kg/day
      (d6-10) induced a significant (P < 0.05) prolongation of the survival time of
      tumor-bearing mice compared with the group given paclitaxel alone. On the other
      hand, treatment with these drugs on the reverse sequence caused toxic deaths of
      all mice. Such sequence-dependent toxic death of mice was also observed with the
      combination of paclitaxel and carboplatin, etoposide or methotrexate. The
      combination of paclitaxel and adriamycin, cyclophosphamide, ranimustine or
      vinblastine (VLB) showed a sequence-independent antitumor activity and a more
      than-additive therapeutic effect was observed with the combination of paclitaxel
      and either VLB or ranimustine. Although the drug administration schedules used
      here may not be directly applicable to the clinic, knowledge of the nature of the
      sequence-dependency in paclitaxel-based combination chemotherapy should be useful
      in the design of clinical trials.

PMID- 10081497
TI  - Effect of electroporation on cell killing by boron neutron capture therapy using
      borocaptate sodium (10B-BSH).
AB  - The cell membrane permeability of 10B-enriched borocaptate sodium (BSH) and the
      extent to which BSH is accumulated in cells are controversial. To elucidate these
      points and to enhance the accumulation of BSH in cells, the effect of
      electroporation on boron neutron capture therapy (BNCT) using BSH was
      investigated. The first group of SCCVII tumor cells was incubated in culture
      medium with 10B-BSH or 10B-enriched boric acid, and exposed to neutrons from the
      heavy water facility of the Kyoto University Reactor. More than 99% of neutrons
      were thermal neutrons at flux base. The second group was pretreated with
      electroporation in combination with 10B-BSH, and thereafter the cells were
      irradiated with neutrons. The cell-killing effect of BNCT was measured by colony
      formation assay. The surviving cell fraction decreased exponentially with neutron
      fluence, and addition of BSH significantly enhanced the cell-killing effect of
      NCT depending on 10B concentration and the preincubation time of cells in the BSH
      containing culture medium. The electroporation of cells with BSH markedly
      enhanced the BNCT effect in comparison with that obtained with preincubation
      alone. The effect of BSH-BNCT with electroporation was almost equal to that of
      BNCT using 10B-boric acid at the same 10B concentration. The effect of BNCT on
      cells pretreated with BSH and electroporation was not reduced by repeated washing
      of the cells before neutron irradiation. Decrease of the effect of BSH-BNCT plus
      electroporation with increase in the waiting time between the electroporation and
      the neutron irradiation could be explained in terms of the extent of cell growth
      during that time. These data suggest that BSH penetrates the cells slowly and
      remains after washing. Electroporation can introduce BSH into the cells very
      efficiently, and BSH thus introduced stays in the cells and is not lost in spite
      of the intensive washing of the cells. Therefore, if electroporation is applied
      to tumors after BSH injection, 10B would remain in the tumors but be cleared from
      normal tissues, and selective accumulation of 10B in tumors will be achieved
      after an appropriate waiting time.

PMID- 10081498
TI  - A proposal for a new histological classification scheme for predicting short-term
      tumor recurrence and death in patients with invasive ductal carcinoma of the
      breast.
AB  - Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma
      (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it
      is extremely important to identify patients at risk of early recurrence or death
      after surgery. The aim of this study was to establish a new histological
      prognostic classification scheme for IDC in order accurately to predict the short
      term outcome. The following histological parameters were analyzed in 201 IDCs: 1)
      tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic
      figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin
      invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion.
      Multivariate analysis showed that nuclear atypia, presence of FF, and the
      invasive length of fat invasion (ILFI) were the most important histological
      parameters correlated with TRR or MR of IDCs. Accordingly, a new histological
      classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat
      invasion, NFF) was devised. Comparative studies were performed with the following
      existing prognostic classifications: 1) histological grade, 2) modified Scarff
      Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM
      (pTNM) stage classifications. Patient grouping defined by NFF classification
      significantly correlated with tumor recurrence or death of IDCs in all cases,
      cases at stages I and II, those without lymph node metastasis and those who were
      estrogen receptor (ER)-positive after adjustment for the other four
      classifications, using multivariate analysis. NFF classification appeared
      superior to existing prognostic classifications for the accurate prediction of
      the short-term outcome for patients with IDCs in low risk groups.

PMID- 10081499
TI  - Cytokines as endogenous pyrogens.
AB  - Cytokines are pleiotropic molecules mediating several pathologic processes. Long
      before the discovery of cytokines as immune system growth factors or as bone
      marrow stimulants, investigators learned a great deal about cytokines when they
      studied them as the endogenous mediators of fever. The terms "granulocytic" or
      "endogenous pyrogen" were used to describe substances with the biologic property
      of fever induction. Today, we recognize that pyrogenicity is a fundamental
      biologic property of several cytokines and hence the clinically recognizeable
      property of fever links host perturbations during disease with fundamental
      perturbations in cell biology. In this review, the discoveries made on endogenous
      pyrogens are revisited, with insights into the importance of the earlier work to
      the present-day understanding of cytokines in health and in disease.

PMID- 10081500
TI  - Susceptibility to infectious diseases: Leishmania as a paradigm.
AB  - The diverse response of individuals within populations to infectious pathogens
      remains poorly understood, although genetic determinants undoubtedly contribute
      in substantial ways to the outcome of infection. In a mouse model of infection
      with the intramacrophage protozoan Leishmania major, susceptibility correlates
      both with aberrant helper T cell differentiation biased towards the production of
      interleukin 4 and with the presence of an endogenous CD4 T cell repertoire that
      recognizes an immunodominant parasite antigen with high frequency. In the setting
      of the particular ecological niche occupied by Leishmania, this combination of
      otherwise unrelated factors synergizes to result in exquisite susceptibility to
      this single pathogen, without seemingly compromising host defenses against other
      agents. Similar paradigms could underlie susceptibility to other pathogenic
      organisms.

PMID- 10081501
TI  - Activation of the neutrophil respiratory burst oxidase.
AB  - The neutrophil respiratory burst oxidase is a multicomponent activatable enzyme
      comprising one of the major phagocyte antimicrobial systems. In the genetic
      disorder chronic granulomatous disease, absent oxidase function is associated
      with recurrent, severe, and often life-threatening infections. The components of
      the oxidase system include both membrane-bound and soluble cytosolic proteins. A
      primary feature of stimulus-dependent activation is the translocation of a
      complex of cytosolic factors to the membrane, where they associate with a
      flavocytochrome enzyme. Interactions among the various oxidase components occur
      through a number of specific regions, including SH3 domains and proline-rich
      motifs. The fully assembled complex functions as an electron transport system,
      moving electrons from cytosolic NADPH to molecular oxygen to form superoxide,
      which, along with subsequent reactive products, exerts microbicidal and cytotoxic
      activities.

PMID- 10081502
TI  - Progress in gene therapy for chronic granulomatous disease.
AB  - Progress in development of gene therapy for chronic granulomatous disease (CGD),
      an inherited defect in leukocyte oxidase deficiency, is reviewed. The use of
      retrovirus vectors to transfer oxidase enzyme subunit cDNA sequence into
      hematopoietic progenitors results in correction of oxidase activity in
      neutrophils differentiating from transduced progenitors. In CGD mouse knockouts
      (X-linked gp91phox-deficient CGD and autosomal recessive p47phox-deficient CGD),
      gene therapy correction of the CGD defect resulted in appearance of oxidase
      normal neutrophils in the peripheral blood and increased host resistance to
      challenge with fungi or bacteria. In a phase I clinical trial of ex vivo gene
      therapy of p47phox-deficient CGD, prolonged production (2-6 months) of a low
      number (1:5000) of oxidase-normal neutrophils was achieved. This therapy might
      prove beneficial in a setting of prolonged infection in CGD patients, in which
      even transient production of autologous gene-corrected neutrophils might augment
      host defense.

PMID- 10081503
TI  - How intracellular bacteria survive: surface modifications that promote resistance
      to host innate immune responses.
AB  - Bacterial pathogens regulate the expression of virulence factors in response to
      environmental signals. In the case of salmonellae, many virulence factors are
      regulated via PhoP/PhoQ, a two-component signal transduction system that is
      repressed by magnesium and calcium in vitro. PhoP/PhoQ-activated genes promote
      intracellular survival within macrophages, whereas PhoP-repressed genes promote
      entrance into epithelial cells and macrophages by macropinocytosis and stimulate
      epithelial cell cytokine production. PhoP-activated genes include those that
      alter the cell envelope through structural alterations of lipopolysaccharide and
      lipid A, the bioactive component of lipopolysaccharide. PhoP-activated changes in
      the bacterial envelope likely promote intracellular survival by increasing
      resistance to host cationic antimicrobial peptides and decreasing host cell
      cytokine production.

PMID- 10081504
TI  - How intestinal bacteria cause disease.
AB  - An improved understanding of how intestinal bacteria cause disease has become
      increasingly important because of the emergence of new enteric pathogens,
      increasing threats of drug resistance, and a growing awareness of their
      importance in malnutrition and diarrhea. Reviewed here are the varied ways that
      intestinal bacteria cause disease, which provide fundamental lessons about
      microbial pathogenesis as well as cell signaling. Following colonization, enteric
      pathogens may adhere to or invade the epithelium or may produce secretory
      exotoxins or cytotoxins. In addition, by direct or indirect effects, they may
      trigger secondary mediator release of cytokines that attract inflammatory cells,
      which release further products, such as prostaglandins or platelet-activating
      factor, which can also trigger secretion. An improved understanding of
      pathogenesis not only opens new approaches to treatment and control but may also
      suggest improved simple means of diagnosis and even vaccine development.

PMID- 10081505
TI  - The pneumococcus at the millennium: not down, not out.
AB  - In the 12 decades that will have elapsed between the first isolation of the
      pneumococcus and the coming millennium, much of fundamental biologic importance
      has been learned from the study of this bacterium and the diseases it causes.
      Streptococcus pneumoniae is associated with the development of Gram's stain, the
      Quellung reaction, and many of the fundamentals of immunology. It has also played
      a significant role in the history of antimicrobial therapy. After a transitory
      period of euphoria engendered by the improved prognosis of pneumococcal pneumonia
      resulting from therapeutic advances, recognition that the newer treatments could
      not bring about the recovery of those sustaining early irreversible physiologic
      injury led to renewed interest in immunoprophylaxis. Added impetus to this
      approach has been fostered by the recent rapid increase in the number of
      pneumococcal isolates resistant to antimicrobial agents and in the magnitude of
      their resistance. Pneumococcal vaccines are increasingly relevant.

PMID- 10081506
TI  - Granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor: comparisons and potential for use in the treatment of
      infections in nonneutropenic patients.
AB  - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) enhance the antimicrobial functions of mature
      neutrophils. G-CSF differs from GM-CSF in its specificity of action on developing
      and mature neutrophils, its effects on neutrophil kinetics, and its toxicity
      profile. The toxicity profile of recombinant (r) GM-CSF is consistent with
      priming of macrophages for increased formation and release of inflammatory
      cytokines, whereas rG-CSF induces production of antiinflammatory factors, such as
      interleukin-1 receptor antagonist and soluble tumor necrosis factor receptors,
      and is protective against endotoxin- and sepsis-induced organ injury. The low
      toxicity of rG-CSF, results of animal models of infection, and extensive
      experience with neutropenic subjects have promoted clinical studies in
      nonneutropenic subjects, which indicate that rG-CSF may be beneficial as
      adjunctive therapy for treatment of serious bacterial and opportunistic fungal
      infections in nonneutropenic patients, including those with alterations in
      neutrophil function.

PMID- 10081507
TI  - Penicillin-binding protein-mediated resistance in pneumococci and staphylococci.
AB  - Target alteration underlies resistance to beta-lactam antibiotics in both
      Staphylococcus species and Streptococcus pneumoniae. The penicillin-binding
      protein (PBP) targets in penicillin-resistant strains of S. pneumoniae are
      modified, low-binding-affinity versions of the native PBPs. Multiple PBP targets
      may be modified by transformation and homologous recombination with DNA from PBP
      genes of viridans streptococci. The level of resistance is determined by how many
      and to what extent targets are modified. In contrast, methicillin resistance in
      staphylococci is due to expression of PBP 2a, a novel, low-affinity PBP for which
      there is no homologue in methicillin-susceptible strains. PBP 2a is encoded by
      mecA, a highly conserved gene most likely acquired by a rare transposition from
      Staphylococcus sciuri or a closely related ancestor. Expression of resistance can
      be highly variable, but this seems not to be determined by PBP modifications.
      Several non-PBP factors are required for high-level resistance.

PMID- 10081508
TI  - Endocarditis at the millennium.
AB  - The members of the Interplanetary Society (Pus Club) have made significant
      contributions to the understanding of the pathogenesis of infective endocarditis
      (IE). Although the incidence of IE has essentially remained unchanged, the
      spectrum and characteristics of patients potentially affected by this disorder
      are expanding. Moreover, in addition to the typical microorganisms implicated in
      IE, there are increasing reports of new or atypical pathogens causing IE,
      including those that are resistant to standard antibiotic therapy. The infectious
      diseases community is challenged to continue to provide effective antimicrobial
      regimens for IE and to further develop diagnostic and surgical strategies to
      identify and treat patients with this disorder. New information is available
      regarding the demographics, diagnostic methods, and therapeutic options for the
      management of IE.

PMID- 10081509
TI  - The flesh-eating bacterium: what's next?
AB  - Since the 1980s, there has been a marked increase in the recognition and
      reporting of highly invasive group A streptococcal (GAS) infections associated
      with shock and organ failure, with or without necrotizing fasciitis. Such
      dramatic cases have been defined as streptococcal toxic shock syndrome
      (StrepTSS). Strains of GAS isolated from patients with invasive disease have been
      predominantly M types 1 and 3, which produce either pyrogenic exotoxin A or B or
      both. The clinical and demographic features of streptococcal bacteremia,
      myositis, and necrotizing fasciitis are presented and compared with those of
      StrepTSS. Current concepts in the pathogenesis of invasive streptococcal
      infection will be presented, with emphasis on the interaction between GAS
      virulence factors and host defense mechanisms. Finally, new concepts in the
      treatment of StrepTSS will be discussed.

PMID- 10081510
TI  - Human experimentation with Neisseria gonorrhoeae: progress and goals.
AB  - Infection with Neisseria gonorrhoeae has adverse consequences for reproductive
      health and facilitates the transmission of the human immunodeficiency virus. A
      major limitation in the development of gonococcal vaccines has been the lack of
      an animal model. Urethral infection can be initiated in male volunteer subjects
      through urethral inoculation. Several hundred patients have participated in
      studies using this experimental infection model. These studies have helped define
      the natural history of experimental infection and provided a better understanding
      of phenotypic and genotypic variation of gonococci in vivo. Isogenic molecular
      mutants can be used to define a role for gonococcal surface structures, including
      pilin and transferrin-binding proteins; recent results demonstrate that gonococci
      unable to express transferrin- and lactoferrin-binding proteins cannot cause
      urethral infection. The experimental model has proven to be an efficient means of
      studying gonococcal infection and focusing vaccine development. In addition, this
      model should allow vaccines to be tested quickly and efficiently.

PMID- 10081511
TI  - Chlamydia trachomatis infections: progress and problems.
AB  - Chalmydia trachomatis infections are the most common bacterial sexually
      transmitted disease in the United States. A substantial proportion of initial
      infections in both men and women are asymptomatic. Use of nucleic acid
      amplification-based diagnostic tests on first-void urine makes it possible to
      initiate community-based screening programs aimed at identifying asymptomatically
      infected men and women. Directly observed single-dose therapy with azithromycin
      is now available. Screening programs have been demonstrated to reduce the overall
      prevalence of chlamydial infection in the tested population and to reduce the
      incidence of subsequent pelvic inflammatory disease in previously screened women.
      The sequelae of chlamydial infections are likely due to immunopathologically
      mediated events in which both the chlamydial 60 kDa heat-shock protein and
      genetic predisposition of specific patients play a role. An improved
      understanding of immunologic events leading to upper genital tract scarring is
      needed to target specific interventions and facilitate development of a vaccine.

PMID- 10081512
TI  - Determinants of the natural history of human immunodeficiency virus type 1
      infection.
AB  - Variation in the time to AIDS and duration of survival of human immunodeficiency
      virus (HIV)-1-infected persons was recognized early in the epidemic. Recent
      studies have indicated that the rate of viral replication, as manifest by the
      number of copies of HIV RNA per milliliter of plasma, is a major determinant of
      outcome in an infected person. The predictive power of the measurement of plasma
      HIV RNA copy number is enhanced by combining this result with the CD4 lymphocyte
      number. The determinants of the rate of viral replication are less clearly
      defined. Recent studies suggest that polymorphism of the chemokine receptors,
      required for cellular infection, plays a role in regulating the rate of viral
      replication. The subsequent adaptive evolution of HIV-1 to the host's immune
      response is a consequence of this dynamic of the virus. Complicating
      opportunistic infections also appear to enhance HIV-1 replication, while
      antiviral therapy, in contrast, can and does suppress viral replication.

PMID- 10081513
TI  - Infection with human immunodeficiency virus, an epidemic out of control: personal
      reflections.

PMID- 10081514
TI  - Nephropathy in type 2 diabetes.
AB  - End-stage renal failure (ESRF) in diabetic patients, mostly type 2, has become
      the most frequent cause of renal replacement therapy in western Europe. The
      majority of patients with type 2 diabetes and renal failure suffer from diabetic
      glomerulosclerosis, but nondiabetic renal disease and atypical presentations,
      e.g. as irreversible acute renal failure or ischaemic nephropathy, play an
      increasingly important role. Known risk factors for the onset of diabetic
      nephropathy include (1) genetic predisposition (indicated by a history of
      hypertension and cardiovascular events in first-degree relatives), (2) quality of
      glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when
      type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in
      approximately 80%. In patients with established diabetic nephropathy,
      hypertension is the most important factor which promotes progression, and this is
      susceptible to intervention. Although less data are available for type 2 diabetes
      (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive
      agent of first choice, but monotherapy is rarely sufficient to achieve the blood
      pressure goal. Although, at least in principle, diabetic nephropathy is a
      preventable condition, currently only a minority of type 2 diabetic patients in
      western Europe receives adequate medical treatment to prevent onset or
      progression of diabetic nephropathy. Consequently, novel approaches to patient
      management and interdisciplinary interaction are necessary to fulfil the
      postulate of the St Vincent declaration concerning prevention of diabetic
      complications.

PMID- 10081515
TI  - Extrahepatic manifestations of chronic hepatitis C infection and the
      interrelationship between primary Sjogren's syndrome and hepatitis C in Swedish
      patients.
AB  - OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of
      chronic hepatitis C virus (HCV) infection in northern European patients,
      including a postulated association between HCV and primary Sjogren's syndrome
      (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmo University
      Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with
      primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES:
      Cryoglobulins were analysed in all patients, while patients with primary SS were
      investigated with regard to markers of HCV infection, and HCV patients with
      objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score,
      sialometry, labial salivary gland biopsy) and antibodies against nuclear
      antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small
      salivary glands from lower lip biopsies were detected by immunohistochemical
      analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates,
      while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates.
      A total of 14/21 (67%) patients with HCV infection had at least one abnormal
      objective test suggestive of xerostomia or keratoconjunctivitis sicca, while
      eight (38%) had objective evidence of both eye and salivary gland involvement.
      HCV antigens were not detected in affected glands. Only two patients had clinical
      symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV
      positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA
      or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While
      involvement of salivary and lacrimal glands was common in Swedish patients with
      HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism
      responsible for glandular inflammation appears to be different from that in
      primary SS. HCV infection does not seem to be an aetiological factor for primary
      SS in this population. These observations suggest that viral, genetic or possibly
      environmental factors may be responsible for the reported high frequencies of
      systemic complications associated with chronic hepatitis C infection in southern
      Europe.

PMID- 10081516
TI  - A comparison of metoprolol and morphine in the treatment of chest pain in
      patients with suspected acute myocardial infarction--the MEMO study.
AB  - OBJECTIVES: To compare the analgesic effect of metoprolol and morphine in
      patients with chest pain due to suspected or definite acute myocardial infarction
      after initial treatment with intravenous metoprolol. DESIGN: All patients,
      regardless of age, admitted to the coronary care unit at Uddevalla Central
      Hospital due to suspected acute myocardial infarction were evaluated for
      inclusion in the MEMO study (metoprolol-morphine). The effects on chest pain and
      side-effects of the two treatments were followed during 24 h. Pain was assessed
      by a numerical rating scale. RESULTS: A total of 265 patients were randomized in
      this prospective double-blind study and 59% developed a confirmed acute
      myocardial infarction. In both treatment groups, there were rapid reductions of
      pain intensity. However, in the patient group treated with morphine, there was a
      more pronounced pain relief during the first 80 min after start of double-blind
      treatment. The side-effects were few and were those expected from each
      therapeutic regimen. During the first 24 h, nausea requiring anti-emetics was
      more common in the morphine-treated patients. CONCLUSION: In suspected acute
      myocardial infarction, if chest pain persists after intravenous beta-adrenergic
      blockade treatment, standard doses of an opioid analgesic such as morphine will
      offer better pain relief than increased dosages of metoprolol.

PMID- 10081517
TI  - Factors associated with the use of various medications amongst patients with
      severe coronary artery disease. SECOR/SBU Project Group.
AB  - AIM: To describe variations by age, sex, symptom severity and hospital region in
      the use of various medications amongst patients with stable angina pectoris who
      are candidates for coronary revascularization. PATIENTS: Patients (n = 2030) with
      chronic stable angina pectoris participating in a national survey evaluating the
      appropriateness of the use of percutaneous transluminal coronary angioplasty
      (PTCA) and coronary artery bypass grafting (CABG). METHODS: As part of a national
      study of the appropriateness of coronary revascularization, data were
      prospectively collected on patients referred for consideration of coronary
      revascularization to seven of the eight public Swedish heart centres that
      performed approximately 92% of all bypass operations in Sweden in 1994. RESULTS:
      Amongst all patients 76% were treated with beta blockers, 41% with calcium
      antagonists and 71% with long-acting nitrates and 70% were treated with at least
      two of these three drugs. Eighty-two per cent of the patients used aspirin and
      14% lipid-lowering drugs. According to logistic regression analysis, with
      medication as the dependent variable and independent variables of age, sex,
      angina functional class, findings at exercise test, history of various diseases
      and region in Sweden where the investigation took place, the most consistent
      factor explaining the use of various medications was found to be geographical
      region. A previous history of acute myocardial infarction (AMI) was also
      associated with the use of all drugs and age was associated with all with the
      exception of beta blockers. Sex was not an independent factor explaining the use
      of any of the drugs. CONCLUSION: In a national survey including patients with
      stable angina pectoris who are potential candidates for coronary
      revascularization, the most important predictor for the use of various
      medications was the geographical region in which the investigation took place.

PMID- 10081518
TI  - Factors predicting clinical remission in adult patients with type 1 diabetes.
AB  - OBJECTIVES: To describe the course of clinical remission in adult patients (16-50
      years of age) with type 1 diabetes and to identify factors predictive of the
      occurrence and length of remission. DESIGN: A retrospective cohort study.
      SUBJECTS: Sixty-two consecutive patients (43 men and 19 women) with new onset
      IDDM, 27 +/- 8 years at diagnosis and treated with multiple insulin injections
      from the beginning. SETTING: Department of Medicine, Uppsala University Hospital
      and Orebro Medical Centre, Sweden. MAIN OUTCOME MEASURES: Length and occurrence
      of remission (defined as maintenance of HbA1c < or = 6.5% and an insulin dosage
      of < or = 0.4 U kg-1 day-1 for a minimum of 1 month) in relation to nine
      biochemical and clinical factors at diagnosis. RESULTS: Sixty-one per cent of the
      patients entered remission. The duration of remission was longer in males than
      females (10 +/- 12 vs. 2 +/- 3 months; P < 0.01). Male gender, normal serum
      bicarbonate at onset and a short time of classic symptoms before onset were
      predictive markers (P < 0.01; P < 0.05 and P < 0.01, respectively) for longer
      duration of remission. Low serum bicarbonate levels at onset were associated with
      lower occurrence of remission. Blood glucose, body mass index (BMI), and age at
      diagnosis did not influence the occurrence or the duration of remission.
      CONCLUSIONS: In most adult patients with new onset of type 1 diabetes remission
      is induced when using multiple insulin injection therapy. Male patients seem
      particularly prone to remission, and the length and extent of beta-cell strain
      prior to diagnosis strongly influences its course.

PMID- 10081519
TI  - Prevalence of the metabolic syndrome in drug-treated hypertensive patients and
      control subjects.
AB  - OBJECTIVES: To determine the prevalence of the metabolic abnormalities associated
      with hypertension and to define the predictors of the metabolic syndrome by
      different definitions in random population-based samples. DESIGN: A cross
      sectional epidemiological study of hypertensive patients and controls. SETTING:
      The participating study subjects visited the research laboratory of the
      Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS: Six
      hundred treated male and female hypertensives aged 40-59 years and 600 age- and
      sex-matched controls were randomly selected by age stratification from population
      registers. MAIN OUTCOME MEASURES: A wide range of laboratory analyses were
      conducted. After fasting blood had been drawn, the subjects were given a 75 g
      glucose load except previously known insulin-treated diabetics. Both 1 h and 2 h
      glucose and insulin concentrations were determined. During the same visit, a
      standardized health questionnaire covering the past medical history, current and
      former medication use, physical activity, smoking habits, alcohol consumption and
      family history was completed. Ten different definitions of the metabolic syndrome
      were applied to achieve a wide perspective of the prevalence of the different
      combinations. RESULTS: The prevalence of the metabolic syndrome in different
      samples varied depending on the definition from 0.8 to 35.3%, being lowest in the
      control men and women and highest in the hypertensive men. Three-quarters of a
      random, middle-aged, urban population show at least one cardiovascular risk
      factor and 91.3% of all the hypertensive subjects show at least one
      cardiovascular risk factor in addition to hypertension itself. The independent
      predictors of the metabolic syndrome were waist circumference, uric acid, total
      cholesterol and gamma-glutamyl transpeptidase in logistic analysis after
      adjustment for age, measure of obesity and gender. CONCLUSIONS: This cross
      sectional, epidemiological study shows that the magnitude of the prevalence rates
      of the metabolic syndrome is at the same level in various populations, being less
      than one-third in population-based samples in spite of the different definitions.
      The cluster of several cardiovascular risk factors, especially in the
      hypertensives, leads to an increased relative risk of cardiovascular diseases.

PMID- 10081520
TI  - Effect of folic acid and betaine on fasting and postmethionine-loading plasma
      homocysteine and methionine levels in chronic haemodialysis patients.
AB  - OBJECTIVES: To study fasting and postmethionine-loading (increment and decrement)
      plasma homocysteine levels in end-stage renal disease (ESRD) patients in relation
      to B-vitamin status and after folic acid treatment without or with betaine.
      DESIGN: Plasma total homocysteine (tHcy) and methionine levels were measured in
      chronic haemodialysis patients after an overnight fast, and 6 and 24 h after an
      oral methionine load (0.1 g kg-1). The patients were subsequently randomized to
      treatment with folic acid 5 mg daily with or without betaine 4 g daily, and the
      loading test was repeated after 12 weeks. The patients were then re-randomized to
      treatment with 1 or 5 mg folic acid daily for 40 weeks, after which a third
      loading test was performed. SETTING: Haemodialysis unit of university hospital
      and centre for haemodialysis. SUBJECTS: Twenty-nine consecutive maintenance (> 3
      months) haemodialysis patients, not on folic acid supplementation, 26 of whom
      completed the study. RESULTS: At baseline, the mean fasting, the 6 h postload and
      the 6 h postload increment plasma tHcy levels were increased as compared with
      those in healthy controls (46.8 +/- 6.9 (SEM), 92.8 +/- 9.1 and 46.0 +/- 4.2
      mumol L-1, respectively) and correlated with serum folate (r = -0.42, P = 0.02; r
      = -0.61, P = 0.001 and r = -0.54, P = 0.003, respectively), but not with vitamin
      B6 or vitamin B12. At week 12, these variables had all decreased significantly.
      Betaine did not have additional homocysteine-lowering effects. At week 52,
      fasting and postload tHcy levels did not differ significantly between patients on
      1 or 5 mg folic acid daily. Plasma tHcy half-life and plasma methionine levels
      after methionine loading were not altered by folic acid treatment. CONCLUSIONS:
      In chronic haemodialysis patients, fasting as well as postmethionine-loading
      plasma tHcy levels depend on folate status and decrease after folic acid therapy.
      Increased postload homocysteine levels in these patients therefore do not
      necessarily indicate an impaired transsulphuration capacity only; alternatively,
      folate may indirectly influence transsulphuration. The elucidation of the complex
      pathogenesis of hyperhomocysteinaemia in chronic renal failure requires further
      investigation.

PMID- 10081521
TI  - Relative importance of improved hospital treatment and primary prevention.
      Results from 20 years of the Myocardial Infarction Register, Goteborg, Sweden.
AB  - OBJECTIVE: To analyse to what extent declines in incidence and mortality of
      coronary artery disease can be attributed to improved hospital and post-hospital
      treatment in contrast to how much is due to primary prevention. DESIGN: A
      register for non-fatal and fatal myocardial infarction and sudden coronary death
      registered in in-hospital as well as out-of-hospital events between 1975 and
      1994. SETTING: City of Goteborg, Sweden, with 450,000 inhabitants. RESULTS:
      Seventy-one per cent of the decline in attacks could be attributed to a decline
      in first infarctions. Of the decrease in coronary deaths, 63% was due to a
      decline in out-of-hospital mortality. Previous registrations for myocardial
      infarction were considerably more common amongst people who died in hospital
      (29%) than amongst those who died out-of-hospital (11-16%) or who survived an
      infarction (11-13%). Out-of-hospital resuscitation contributed to about half of
      the reduction in out-of-hospital mortality. Thus, most of the decline in
      incidence and about half of the decline in sudden coronary deaths was due to
      primary preventive measures. Population data on risk factors indicate a decline
      of 37% between 1963 and 1995 in coronary risk amongst consecutive cohorts of 50
      year-old men in the community. CONCLUSION: Out-of-hospital resuscitation,
      treatment in coronary care units and post-infarct treatment improved
      considerably, but changes in primary risk factors were also of major importance
      for the decline in incidence and mortality.

PMID- 10081522
TI  - Effects of diabetes mellitus on patients with acute intermittent porphyria.
AB  - OBJECTIVES: To study the effects of diabetes mellitus in patients with acute
      intermittent porphyria (AIP). Haeme deficiency in the liver of AIP patients
      stimulates an increase in ALA-synthase which triggers an escalating metabolic
      chain reaction, leading to an increase in the porphyrin content. This reaction
      can be reduced by treating AIP patients with haeme arginate or with glucose.
      DESIGN: A population-based study of all patients > 18 years of age having DNA
      verified AIP (n = 328) living in the two most northerly counties of Sweden
      (Norrbotten and Vasterbotten, with 550,000 inhabitants) of whom 16 had type 2
      diabetes. Prevalence of diabetes was studied retrospectively in 26 AIP patients
      with hepatocellular carcinoma (HCC). RESULTS: None of the patients showed
      symptoms of AIP after the onset of their diabetes. Three patients had had
      recurrent, severe attacks for many years but when their diabetes became manifest,
      their urinary ALA and PBG levels decreased and the AIP symptoms resolved, to the
      relief of the patients. Amongst the 26 AIP patients with HCC, only one with signs
      of diabetes was identified (impaired glucose tolerance test). CONCLUSIONS: This
      study raises the possibility that diabetes mellitus may be beneficial for
      patients with severe AIP.

PMID- 10081523
TI  - Postpartum onset of acute heart failure possibly due to postpartum autoimmune
      myocarditis. A report of three cases.
AB  - Autoimmune diseases, especially autoimmune thyroid disease, frequently develop
      after delivery due to the immune rebound mechanism. Most cases have transient
      dysfunction of affected organs. Cardiac dysfunction developed after delivery is
      called postpartum or peripartum cardiomyopathy. However, the aetiology of the
      disease is not clarified yet. Here we report three cases that developed acute
      heart failure in the postpartum period. One was complicated with an
      atrioventricular block and postpartum autoimmune thyroiditis. All patients
      recovered to normal cardiac function or pre-attack condition after 1 month of
      therapy with conventional drugs and bed rest. All three had positive antiheart
      antibody detected by indirect immunofluorescence assay, and one had antibody to
      heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two
      patients examined revealed lymphocytic infiltration by endomyocardial biopsy.
      Antibodies to 26 viruses were not elevated significantly during the first 2 weeks
      after admission in any case. It is strongly suggested that heart failure is
      induced by postpartum autoimmune myocarditis, and thus clinicians should be aware
      of this disease.

PMID- 10081524
TI  - Cultured keratinocytes in in vitro dermatotoxicological investigation: a review.
AB  - The keratinocyte is responsible for the architecture of the epidermis, that
      portion of the skin that forms the environmental barrier necessary for survival.
      It also interacts with other cell types in the epidermis in response to various
      environmental influences. This cell type is used frequently for in vitro
      cutaneous toxicological investigations as an alternative to whole-animal studies.
      Several areas of cutaneous research using cultured keratinocytes are germane as
      regards the scope of this journal. The following areas of biomedical research
      were reviewed: (1) dermatotoxicology, including environmental chemicals,
      antiseptics, drugs, metals, and pesticides; (2) immunotoxicology, including
      inflammation and allergic dermatitis; (3) radiation, including ultraviolet and x
      irradiation; and (4) the development of assays as alternatives to whole-animal
      testing. Due to the abundance of such investigations reported in the last 30
      years, this review is limited mainly to reviewing reports published in this
      decade.

PMID- 10081525
TI  - Ozone-induced lung inflammation and mucosal barrier disruption: toxicology,
      mechanisms, and implications.
AB  - The airway epithelial lining serves as an efficient barrier against penetration
      of exogenous particles and macromolecules. Disruption of this barrier following
      O3 exposure represents a state of compromised epithelial defenses leading to
      increased transmucosal permeability. Although the barrier disruption following an
      acute exposure is transient in nature, the brief period of disruption caused by
      O3, an oxidant air pollutant, provides an opportunity for facilitated entry of a
      potentially toxic particulate copollutant(s) across the airway epithelia. The
      subsequent deposition and retention of the copollutant(s) in the subepithelial
      compartment for prolonged periods adds the risk of injury due to chronic exposure
      following an acute episode. Toxicological studies from several laboratories have
      demonstrated alterations in epithelial permeability, suggestive of barrier
      disruption, in animals and humans exposed to O3. Inflammatory cells represent
      another important component of pulmonary defenses, but upon activation these
      cells can both induce and sustain injury. The recruitment of these cells into the
      lung following O3 exposure presents a risk of tissue damage through the release
      of toxic mediators by activated inflammatory cells. Several studies have reported
      concomitant changes in permeability and recruitment of the inflammatory cells in
      the lung following O3 exposure. In these studies, an inflammatory response, as
      detected by an increase in the number of polymorphonuclear leukocytes in the
      bronchoalveolar lavage (BAL) or in lung parenchyma, was accompanied by either an
      increased tracer transport across the airway mucosa or an elevation in the levels
      of total protein and/or albumin in the BAL. The magnitude of response and the
      time at which the permeability changes and inflammatory response peaked varied
      with O3 concentration, exposure duration, and the mode of analysis. The
      responsiveness to O3 also appeared to vary with the animal species, and increased
      under certain conditions such as physical activity and pregnancy. Some of the
      effects seen after an acute exposure to O3 were modified upon repeated exposures.
      The responses following repeated exposures included attenuation, persistence, or
      elevation of permeability and inflammation. Mechanistic studies implicate
      chemotactic factors, cellular mediators, and cell-surface-associated molecules in
      the induction of inflammation and lung injury. In discussing these studies, this
      review serves to introduce the mucosal barrier functions in the lung, evaluates
      inflammatory and permeability consequences of O3, addresses mechanisms of
      inflammatory reactions, and offers alternate viewpoints.

PMID- 10081526
TI  - Reduction of chromium(VI) and its relationship to carcinogenesis.
AB  - Although Cr(VI)-containing compounds are well-documented carcinogens, their
      mechanism of action is still not well understood. Recent studies have suggested
      that reduction of Cr(VI) to its lower oxidation states and related free-radical
      reactions play an important role in carcinogenesis. This article summarizes
      recent studies on (1) the reduction of Cr(VI) by ascorbate, diol- and thiol
      containing molecules, certain flavoenzymes, cell organelles, intact cells, and
      whole animals; (2) free-radical production with emphasis on hydroxy radical
      generation via Fenton or Haber-Weiss type reactions; and (3) free-radical-induced
      cellular damage, such as DNA strand breaks, hydroxylation of 2'-deoxyguanosine,
      and activation of nuclear transcription factor kappa B.

PMID- 10081527
TI  - Paracetamol--misused good old drug?

PMID- 10081528
TI  - Paracetamol 1 g given rectally at the end of minor gynaecological surgery is not
      efficacious in reducing postoperative pain.
AB  - BACKGROUND: We studied the analgesic effects of 1 g paracetamol given rectally at
      the end of surgery in a prospective, randomised, double-blind study. METHODS: One
      hundred and forty ASA I-II women scheduled for elective termination of pregnancy
      under general anaesthesia were randomly allocated to receive paracetamol or
      placebo. All patients had standardised anaesthesia with propofol, fentanyl and
      oxygen in nitrous oxide. Postoperative pain was assessed by VAS score. RESULTS:
      We could find no difference regarding postoperative pain, need for analgesics or
      time to discharge between the groups. CONCLUSION: The routine use of 1 g
      paracetamol given rectally at the end of surgery after termination of pregnancy
      seems not to be justified.

PMID- 10081529
TI  - Intra-articular morphine for pain relief after knee arthroscopy.
AB  - BACKGROUND: Peripheral opioid analgesia is well documented. But the clinical
      usefulness of intra-articular morphine after surgery is uncertain. The aim of the
      present study was to evaluate the analgesic effects of intra-articular morphine
      after knee arthroscopy. METHODS: In this parallel-group, double-blind study, 90
      patients were randomised to receive either morphine 1 mg, morphine 2 mg or
      placebo in 5 ml saline intra-articularly at the end of arthroscopic knee surgery.
      Anaesthetic technique was local infiltration and intra-articular injection of
      lidocaine. Analgesic efficacy was evaluated by a global pain score, pain
      intensity (visual analogue scale), and analgesic requirements (paracetamol)
      during the first 48 h postoperatively. RESULTS: No significant differences
      between the groups were found for any of the efficacy variables. A majority of
      the patients had mild pain throughout the study, thus possibly compromising study
      sensitivity. In a subgroup with more intense pain early after arthroscopy, intra
      articular morphine 2 mg reduced pain intensity (P < 0.05) and analgesic
      requirements (P < 0.05) compared with placebo. CONCLUSION: Postoperative
      analgesic effect of intra-articular morphine was found only in a subgroup of
      patients with higher pain intensity in the immediate postanaesthetic period.
      Possible reasons for our overall negative findings include low study sensitivity
      due to weak pain stimulus, lack of inflammation that may be a prerequisite for
      peripheral opioid analgesia, and the local anaesthetic, which impedes local
      inflammatory reaction and expression of peripheral opioid receptors. These
      factors may also explain the conflicting results in other studies.

PMID- 10081530
TI  - Continuous interscalene brachial plexus block for postoperative analgesia
      following shoulder surgery.
AB  - BACKGROUND: Severe postoperative pain is a well-known problem following shoulder
      surgery. This study evaluates the clinical efficacy of continuous interscalene
      brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.)
      for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled
      for acromioplasty during general anesthesia, were randomly allocated to one of
      three different postoperative pain management groups. Group MO received morphine
      (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL
      received a continuous interscalene brachial plexus block with bupivacaine (1.25
      mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia
      with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS,
      circulatory and respiratory stress parameters (heart rate, systemic arterial
      pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol
      by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group
      was effective (VAS < 3) and significantly more potent than in groups MO and PCA,
      except at 16 and 20 h. Lactate was significantly increased in the PL group,
      glucose was significantly increased in all groups, while glycerol showed a
      variable pattern. There were no significant stress metabolite differences among
      groups. VAS showed no statistical correlation with microdialysate, respiratory or
      circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus
      block provides very good pain relief following shoulder surgery and is superior
      to the other methods studied. However, we were unable to demonstrate a
      correlation between VAS pain scores and stress indicators in metabolic,
      circulatory and respiratory parameters.

PMID- 10081531
TI  - Comparative effects of intravenous ketorolac and pethidine on perioperative
      analgesia and postoperative nausea and vomiting (PONV) for paediatric strabismus
      surgery.
AB  - BACKGROUND: Corrective strabismus surgery is associated with moderate pain and a
      very high incidence of postoperative nausea and vomiting (PONV). Ketorolac
      tromethamine, a nonsteroidal anti-inflammatory drug, is a popular analgesic in
      adults. There are only limited published data on the use of intravenous ketorolac
      for paediatric analgesia perioperatively. This study evaluated and compared the
      emetic and analgesic effect of ketorolac with pethidine and its suitability for
      this kind of surgery. METHODS: Following institutional ethics committee approval
      and parental consent, 52 ASA class I children of age 2.5 to 15 yr were randomised
      to receive either ketorolac 0.9 mg kg-1 or pethidine 0.5 mg kg-1 given
      intravenously (i.v.). A blinded observer assessed recovery by Steward's method
      immediately after arrival at the post anaesthesia care unit (PACU), pain by
      validated Objective Pain Score (OPS) at 0 h, 1/2 h and 1 h after arrival at the
      PACU and PONV by Numeric Rank Score at specified time intervals. RESULTS: There
      were no differences in demographic data, anaesthesia time or surgery duration.
      Recovery scores, OPS and postoperative analgesic requirement were similar in both
      groups. PONV at various time intervals for the first 24 h, occurred more
      frequently in the pethidine group as compared to the ketorolac group (P < 0.001)
      There were no side effects observed with either drug. CONCLUSION: Ketorolac in a
      dose of 0.9 mg kg-1 i.v. at the induction of anaesthesia is as effective as
      pethidine 0.5 mg kg-1 i.v. as an analgesic and is associated with significantly
      less PONV.

PMID- 10081532
TI  - Effect and placebo effect of acupressure (P6) on nausea and vomiting after
      outpatient gynaecological surgery.
AB  - BACKGROUND: Acupuncture and acupressure have previously been reported to possess
      antiemetic effect. We wanted to investigate the "true" and placebo effect of
      acupressure in prevention of postoperative nausea and vomiting (PONV). PATIENTS
      AND METHODS: Sixty women undergoing outpatient minor gynaecological surgery were
      entered into a double-blind and randomised study. One group received acupressure
      with bilateral stimulation of P6 (A), a second group received bilateral placebo
      stimulation (P) and a third group received no acupressure wrist band and served
      as a reference group (R). PONV was evaluated as number of patients with complete
      response (no PONV), nausea only or vomiting. In addition, the need for rescue
      antiemetic medication and nausea after 24 h was registered. RESULTS: Complete
      response was obtained in 11, 11 and 9 patients in groups, A, P and R,
      respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1
      and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in
      A, P and R groups, respectively. When compared to placebo acupressure (2 patients
      vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue
      antiemetic medication after acupressure at P6 (no vomiting or rescue medication).
      When compared to the observation group (5 vomited and 4 needed rescue
      antiemetics), significantly fewer vomited after acupressure (P < 0.05)
      CONCLUSION: In patients undergoing brief gynaecological surgery, placebo effect
      of acupressure decreased nausea after 24 h but vomiting and need of rescue
      antiemetics was reduced only by acupressure with the correct P6 point
      stimulation.

PMID- 10081533
TI  - The role of nitric oxide in sepsis--an overview.
AB  - Nitric oxide (NO) is normally produced in the endothelium by the constitutive
      isoform of the NO synthase. This physiological production of NO is important for
      blood pressure regulation and blood flow distribution. Several lines of evidence
      suggest that a hyperproduction of NO by the inducible form of NO synthase (iNOS)
      may contribute to the hypotension, cardiodepression and vascular hyporeactivity
      in septic shock. Lipopolysaccarides and cytokines, such as tumor necrosis factor,
      interleukin-1 and interferon-gamma, have been shown to induce iNOS in the
      endothelium, vascular smooth muscle cells, macrophages and different parenchymal
      cells. Treatment with inhibitors of NO synthesis has been shown to improve
      hemodynamic variables and survival in several animal models of septic shock. In
      human septic shock, inhibition of NO synthesis has been shown to alter
      hemodynamic variables in short-term studies, but it is uncertain whether this
      treatment has beneficial long-term effects. The aim of this review is to give an
      overview of the physiological role of NO and to discuss the role of NO in sepsis
      and the potential therapeutic implications of NO as a target in treatment of
      human septic shock. A main new aspect of this review is a critical discussion of
      previous reports measuring plasma nitrite/nitrate during septic shock and an
      evaluation of the validity of interpreting these data as evidence for a
      hyperproduction of NO. This review also emphasizes that many septic patients have
      preexisting endothelial dysfunction and lung diseases, which may contribute to
      adverse effects by systemic inhibition of NO synthesis. Another new aspect of the
      present review is a focus on the lack of direct evidence of iNOS expression in
      human septic shock.

PMID- 10081534
TI  - Production of nitrogen dioxide during nitric oxide therapy using the Servo
      Ventilator 300 during volume-controlled ventilation.
AB  - BACKGROUND: Inhaled nitric oxide may be useful in the treatment of pulmonary
      hypertension and hypoxaemia. Nitric oxide is rapidly oxidized to nitrogen
      dioxide, which is toxic and may adversely affect the airways of the patient. The
      aim of the present investigation was to examine factors that may affect the
      concentration of nitrogen dioxide, using the Servo Ventilator 300 nitric oxide
      delivery system, where nitric oxide is flow-proportionally mixed with the main
      ventilatory flow in the proximal part of the inspiratory limb. METHODS: In this
      experimental study nitric oxide and nitrogen dioxide levels were measured at the
      inspiratory site of a Y-piece with a chemiluminescence analyzer and
      electrochemical fuel cells. The effects of different concentrations of nitric
      oxide and oxygen, minute volume, different tube lengths, a soda lime absorber,
      and a humidifier placed in the inspiratory limb were evaluated. RESULTS: The
      concentration of nitrogen dioxide was dependent on the concentrations and
      residence time of nitric oxide with oxygen and the minute volume ventilation
      used. A soda lime absorber reduced concentrations of nitrogen dioxide at the
      expense of almost corresponding reductions in inhaled concentrations of nitric
      oxide. A humidifier increased the concentration of nitrogen dioxide, to an extent
      depending on the water volume and temperature used. CONCLUSION: Concentrations of
      nitric oxide and oxygen, minute volume ventilation, and residence time in the
      inspiratory part of the ventilatory circuit were factors that affected the
      generation of nitrogen dioxide. A soda lime absorber in this system is not
      recommended.

PMID- 10081535
TI  - Positive end-expiratory pressure prevents atelectasis during general anaesthesia
      even in the presence of a high inspired oxygen concentration.
AB  - BACKGROUND: General anaesthesia impairs the gas exchange in the lungs, and
      moderate desaturation (SaO2 86-90%) occurred in 50% of anaesthetised patients in
      a blinded pulse oximetry study. A high FiO2 might reduce the risk of hypoxaemia,
      but can also promote atelectasis. We hypothesised that a moderate positive end
      expiratory pressure (PEEP) level of 10 cmH2O can prevent atelectasis during
      ventilation with an FiO2 = 1.0. METHODS: Atelectasis was evaluated by computed
      tomography (CT) in 13 ASA I-II patients undergoing elective surgery. CT scans
      were obtained before and 15 min after induction of anaesthesia. Then, recruitment
      of collapsed lung tissue was performed as a "vital capacity manoeuvre" (VCM,
      inspiration with Paw = 40 cmH2O for 15 s), and a CT scan was obtained at the end
      of the VCM. Thereafter, PEEP = 0 cmH2O was applied in group 1, and PEEP = 10
      cmH2O in group 2. Additional CT scans were obtained after the VCM. Oxygenation
      was measured before and after the VCM. RESULTS: Atelectasis (> 1 cm2) was present
      in 12 of the 13 patients after induction of anaesthesia. At 5 and 10 min after
      the VCM, atelectasis was significantly smaller in group 2 than group 1 (P <
      0.005). A significant inverse correlation was found between PaO2 and atelectasis.
      CONCLUSIONS: PEEP = 10 cmH2O reduced atelectasis formation after a VCM, when FiO2
      = 1.0 was used. Thus, a VCM followed by PEEP = 10 cmH2O should be considered when
      patients are ventilated with a high FiO2 and gas exchange is impaired.

PMID- 10081536
TI  - Intraoperative glucose administration influences respiratory quotient during
      paediatric anaesthesia.
AB  - BACKGROUND: Oxidation of carbohydrates and fat yields respiratory quotients (RQ)
      of 1.0 and 0.7 respectively. Maintained or increased blood glucose concentrations
      are usually seen during paediatric anaesthesia and surgery even without glucose
      administration. The aim of the present study was to evaluate whether an
      intraoperative glucose infusion influences the RQ as an indication of a different
      metabolic preference in comparison to a glucose-free fluid regime. METHODS:
      Eighteen children between 0.5 and 24 months of age were studied during
      anaesthesia with controlled ventilation, oxygen in air, isoflurane, thiopentone,
      atracurium and fentanyl. Oxygen consumption and carbon dioxide production were
      measured using indirect calorimetry All children received Ringer acetate as
      needed; in addition, nine children were given glucose 10%, 3 ml.kg-1.h-1,
      corresponding to 300 mg.kg-1.h-1. Blood samples for analyses of glucose, lactate,
      free fatty acids and ketones were taken before and during surgery. RESULTS: RQ
      was significantly higher in the children given glucose 0.92 +/- 0.08, compared to
      0.81 +/- 0.06 in the children without glucose (P < 0.01). Oxygen consumption
      tended to be higher, although not significantly so, in patients without glucose
      infusion. Energy expenditure was 1.70 +/- 0.29 kcal.kg-1.h-1, without significant
      group differences. Higher blood glucose concentrations during surgery were found
      in the children given glucose. CONCLUSIONS: Our results indicate a higher glucose
      oxidation rate in patients given glucose during surgery.

PMID- 10081537
TI  - A simplified method for separate measurements of lung and chest wall mechanics in
      ventilator-treated patients.
AB  - BACKGROUND: Airway pressure measurements above the endotracheal tube will be
      distorted because of endotracheal tube resistance. To separate lung and chest
      wall compliance, esophageal pressure is conventionally measured with an air
      filled balloon catheter, which is difficult to insert in unconscious patients. We
      have developed a methodology with fluid-filled catheters for intratracheal and
      esophageal pressure measurements. METHODS: Twelve anesthetized patients were
      studied. Tidal volumes were measured by side-stream spirometry. Airway pressures
      were measured at the Y-piece and in the trachea with fluid-filled pressure lines.
      Esophageal pressure was measured via the narrow lumen in a fluid-filled Salem
      double-lumen stomach tube, which was slowly retracted from the stomach up through
      the esophagus until maximal respiratory pressure readings and minimal cardiac
      artifacts were obtained. Lung mechanics were measured at different tidal volumes
      (TV) and positive end-expiratory pressure (PEEP). RESULTS: There was a
      significant difference between airway pressures at the Y-piece and in the
      trachea. Total compliance significantly increased with increasing TV and
      decreased with increasing PEEP. Chest wall compliance increased significantly
      with increasing TV, while lung compliance did not change significantly. Two
      patients showed repeatedly marked increase in lung compliance at one specific
      ventilatory setting, an increase the proportion of which was not reflected by
      changes in total compliance. CONCLUSIONS: Y-piece pressures are not
      representative of intratracheal pressures, which can be measured by inserting a
      fluid-filled pressure line through the tube. Esophageal pressure is easily
      recorded with a fluid-filled Salem double-lumen catheter. Large changes in lung
      compliance may pass unnoticed when only total compliance is monitored. Monitoring
      of lung compliance may offer an improved basis for decisions about ventilator
      settings.

PMID- 10081538
TI  - Irrigating fluid absorption during percutaneous nephrolithotripsy.
AB  - BACKGROUND: The most common complication during percutaneous nephrolithotripsy
      (PNL) is the destruction of organ structures with extravasation of the irrigation
      fluid into the retroperitoneal space. Consequently, there is an increased risk of
      a urosepsis and a complicated therapeutic course. In this study we aimed to show
      that extravascular absorption could be differentiated from intravascular
      absorption due to their unique absorption characteristics, and that these
      characteristics enable a prediction of possible post-operative complications.
      METHODS: In a prospective study of 31 patients with PNL, ethanol was added to the
      irrigating fluid and blood ethanol concentration (BEC) was measured by gas
      chromatography during the endoscopic procedure and in the recovery room.
      Following the guidelines of Hahn, patients were divided into two groups: group
      EVA, in whom extravasation had occurred with subsequent absorption; group IVA,
      those with intravascular absorption. Patients' post-operative progress along with
      diagnoses of renal perforations or bleeding, or signs of infection or sepsis,
      were comprehensively listed. RESULTS: EVA was diagnosed in 19 cases, and IVA in
      12 cases. Maximum BEC levels were achieved after 20 min (median) in the IVA
      group, and 75 min in the EVA group (P < 0.05). Apart from their significantly
      higher demand for opioids (P < 0.05), EVA patients had been hospitalised for a
      substantially and significantly longer period of time (P < 0.01). Although
      without statistical significance, there was a higher rate of peri-operatively
      confirmed complications and prolonged intensive therapeutic treatment in the
      extravasation group. CONCLUSION: Retroperitoneal extravasation can be identified
      by using ethanol monitoring during and after PNL. Afflicted patients require
      considerably longer hospitalisation, probably because of the additional injury to
      surrounding organ structures.

PMID- 10081539
TI  - Expiratory flow-volume curves in mechanically ventilated patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Forced expiratory flow-volume curves are commonly used to assess the
      degree of airflow obstruction in patients with chronic obstructive pulmonary
      disease (COPD). In mechanically ventilated subjects, expiratory airways
      obstruction can only be estimated from relaxed expirations. The aim of this study
      was to quantify the degree of airways obstruction from relaxed expiratory flow
      volume curves in mechanically ventilated patients with COPD. METHODS: As measure
      of airflow obstruction, the effective time constant during the last 50% of
      expired volume (tau) was calculated. For bedside monitoring, tau was recalculated
      as the slope of the flow during the last 50% of expired volume (SF50). In order
      to study reproducibility, the variables were calculated from consecutive breaths
      and at different levels of end-expiratory lung volume (EEV). The SF50 and the tau
      were correlated with the forced expiratory volume in 1 s (FEV1) measured prior to
      the start of ventilatory support. RESULTS: Twenty-seven patients were studied
      with a FEV1 expressed as percentage predicted of 31 +/- 12% (mean +/- SD). The
      SF50 amounted to 19 +/- 10 degrees. A positive linear correlation was established
      between SF50 and the FEV1, (%pred), (r = 0.90, P < 0.0001). The tau showed an
      exponential relationship with FEV1 (%pred), (r2 = 0.78). From 5 consecutive
      breaths the mean variation coefficient of SF50 was 5 +/- 2%. Changes of delta EEV
      from 0.05 to 1.00 L did not affect the SF50-values. In 12 patients, mechanically
      ventilated for respiratory diseases other than COPD, mean tau and SF50 were
      significantly different from the COPD-patients (P < 0.0001). CONCLUSIONS: This
      study indicates that relaxed expiratory flow-volume curves can be used to assess
      airflow obstruction in mechanically ventilated patients with COPD. This
      information can be used to adapt ventilatory settings.

PMID- 10081540
TI  - Venous gas embolism: detection with pulsed Doppler guided by two-dimensional
      echocardiography.
AB  - BACKGROUND: Venous gas embolism is a rare but severe event in critically ill
      patients and the diagnosis should be obtained as soon as possible.
      Ultrasonography is a sensitive, non-invasive, and bedside means of detection.
      METHOD: We prospectively estimated the performance of two-dimensional (2D)
      echocardiography and pulsed Doppler guided by 2D echocardiography in the
      detection of venous embolism. We used, as a model of venous gas embolism, the
      decompression following a recreational dive. This activity is responsible for
      circulating bubbles related to nitrogen desaturation. RESULTS: Venous gas emboli
      were detected following 44 of 68 dives in 20 of 24 divers. Gas emboli in 36 cases
      (16 divers) was shown by 2D echocardiography. Parasternal short-axis and right
      cavity longitudinal views were the best views for positive detection. Pulsed
      Doppler confirmed the existence of venous gas emboli in all of the 36 cases with
      positive detection by 2D echocardiography. In 8 other cases, pulsed Doppler
      detected circulating bubbles, which were not observed by using 2D
      echocardiography. Discrepancies were observed in 4 divers with an echographic
      image of medium or poor quality. CONCLUSION: Combined utilization of 2D
      echocardiography and pulsed Doppler provides a better method for the detection of
      venous gas embolism than 2D echocardiography alone. This protocol could be used
      for critically ill patients suspected of venous air embolism.

PMID- 10081541
TI  - Influence of temperature on tracheal tube cuff pressure during cardiac surgery.
AB  - BACKGROUND: Lateral wall pressure may cause tracheal injury by affecting tracheal
      capillary blood flow. Damage to the trachea is less severe when lateral wall
      pressure exerted by the endotracheal tube cuff does not exceed the mean capillary
      perfusion pressure of the mucosa. The purpose of this study was to determine the
      effects of hypothermic and normothermic cardiopulmonary bypass (CPB) on tracheal
      tube cuff pressure dynamics. METHODS: Twenty-two patients were studied during
      normothermic CPB (pulmonary artery blood temperature in the CPB period between 36
      and 35 degrees C), and 22 patients during hypothermic CPB (pulmonary artery
      temperature in the CPB period between 32 and 28 degrees C). A Mallinckrodt
      Medical Lo-Contour Murphy tracheal tube, with high-volume, low-pressure cuff was
      used without lubricant. Intracuff pressure (ITCP) was recorded at end-expiration
      before, during and after cardiopulmonary bypass. RESULTS: ITCP measurements were
      different between groups during CPB at aortic cross-clamping (13.9 +/- 0.8 mmHg
      in the normothermic group versus 11.3 +/- 0.4 mmHg in the hypothermic group, P <
      0.05), and respectively during CPB after aortic declamping (15.3 +/- 0.8 mmHg and
      12.6 +/- 0.8 mmHg, P < 0.05) and after CPB at the end of surgery (16.8 +/- 0.7
      mmHg and 18.6 +/- 0.3 mmHg, P < 0.05). CONCLUSION: We conclude that the ITCP is
      higher in normothermic CPB than in hypothermic CPB; however, the clinical
      significance of this observation needs further investigation.

PMID- 10081542
TI  - Effects of small peripheral temperature changes on the evoked baseline
      electromyographic response.
AB  - BACKGROUND: Since muscle temperature seems to influence the electrically evoked
      compound muscle action potentials, we wanted to quantificate the effect of light
      external cooling and warming on evoked responses in a clinical setting. METHODS:
      In ophthalmic surgical patients (ASA I-III), evoked electromyographic (EMG)
      responses to supramaximal train-of-four stimuli were measured once a minute.
      After obtaining an initial baseline (100%) where temperatures of the first dorsal
      interosseal muscle and the skin above it had stabilised, the patients' hands were
      cooled to stable temperatures by a blower (room air). A new baseline was
      established and, subsequently, the hand re-warmed to the starting temperature.
      The cooling procedure was repeated, operation time allowing. RESULTS: The mean
      (range) muscle and skin temperature changes were from 36.0 degrees C (35.5-37.1)
      to 34.6 degrees C (33.2-36.1) and 35.7 degrees C (35.0-36.7) to 32.0 degrees C
      (29.4-35.6), respectively. The mean (range) change of the EMG-response was
      8.0%/degree C (0.3-16.5) for the muscle and 4.1%/degree C (0.3-37.9) for the
      skin. Wide individual variability was evident. CONCLUSION: The electrically
      evoked EMG-response is sensitive to even small changes in temperature at the
      measurement site. Therefore, when applying the evoked EMG in neuromuscular
      studies, peripheral skin or muscle temperatures need to be monitored, and
      attempts to stabilise the temperature of the monitored muscles should be made.

PMID- 10081543
TI  - The effect on intraocular pressure of endotracheal intubation or laryngeal mask
      use during TIVA without the use of muscle relaxants.
AB  - BACKGROUND: Depolarizing and non-depolarizing muscle relaxants possess many
      untoward side effects. In most patients endotracheal intubation may be performed
      with a propofol and alfentanil combination. The purpose of this study was to
      compare the effect on intraocular pressure (IOP) and haemodynamics of
      endotracheal (ET) intubation or laryngeal mask (LMA) insertion during total
      intravenous anaesthesia (TIVA) without the use of muscle relaxants. METHODS: In a
      randomised study, 20 patients scheduled for elective orthopaedic surgery were
      assigned to two groups of 10 patients. Anaesthesia was induced with i.v.
      alfentanil 40 micrograms/kg and propofol 2.5 mg/kg. LMA insertion or ET
      intubation was achieved by the same anaesthesiologist. Airway score, insertion
      score, patient response and haemodynamics were recorded. IOP measurements were
      recorded before and after induction, 1 and 2 min after ET intubation or LMA
      insertion, and 1 and 2 min after extubation. RESULTS: Mean arterial pressure and
      heart rate after insertion of the airway management devices was significantly
      higher than induction values in the ET group (P < 0.05), while during 2-3 min no
      significant changes were observed in LMA group. In all patients following
      propofol and alfentanil induction, IOP was significantly lower than preinduction
      values (P < 0.001). IOP following extubation was significantly higher than
      preinduction values in the ET group, but not in the LMA group (P < 0.001).
      CONCLUSION: During TIVA without the use of muscle relaxants neither LMA insertion
      nor ET intubation increased the IOP, but ET extubation did.

PMID- 10081544
TI  - Effects of sevoflurane and isoflurane anesthesia on arterial ketone body ratio
      and liver function.
AB  - BACKGROUND: The purpose of this study was to compare the effect on arterial
      ketone body ratio (AKBR), which indicates hepatic mitochondrial energy charge in
      relation to hepatic blood flow, and liver function test (serum levels of liver
      enzymes) between sevoflurane and isoflurane anesthesia. METHODS: Serum levels of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin
      (TBil), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GTP), and
      lactate dehydrogenase (LDH) were measured before and 1,2,3,7, and 14 days after
      anesthesia in each of 60 patients receiving either sevoflurane or isoflurane
      anesthesia for neurosurgery (tumor resection). In 13 patients of both groups,
      arterial concentrations of acetoacetate and 3-hydroxybutyrate were also measured
      before, during and after (up to 12 h) anesthesia and the AKBR was calculated.
      RESULTS: AST, ALT and GTP increased, peaking 7 days after anesthesia, especially
      in the isoflurane group. There was a significantly greater number of patients
      with abnormal AST and ALT values in the isoflurane group than in the sevoflurane
      group. The increase of TBil had its peak 1 day after anesthesia in both groups.
      AKBR decreased after anesthesia induction and recovered to the control value 12 h
      after anesthesia in both groups. There was no difference between the two
      anesthetic groups in AKBR. CONCLUSION: Isoflurane induced an elevation of serum
      levels of liver enzymes more frequently than did sevoflurane 3 to 14 days after
      anesthesia, while AKBR until 12 h after anesthesia did not show any significant
      difference between sevoflurane and isoflurane anesthesia.

PMID- 10081545
TI  - Ventricular fibrillation related to reversal of the neuromuscular blockade in a
      patient with long QT syndrome.
AB  - The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden
      death at a young age due to ventricular fibrillation. We report a patient with an
      undiagnosed LQTS who had an episode of cardiac arrest during the final part of
      general anesthesia, immediately after the drugs for reversal of the neuromuscular
      blockade were given. We suggest that the administration of glycopyrronium might
      have been the provoking factor in this patient.

PMID- 10081546
TI  - One-lung ventilation when intubation is difficult--presentation of a new
      endobronchial blocker.
AB  - BACKGROUND: One-lung ventilation utilizing a double-lumen endotracheal tube may
      be technically difficult or inappropriate in morbidly obese or critically ill
      patients. In patients requiring awake fiberoptic intubation, double-lumen tube
      placement may be impossible. Wire-guided endobronchial blockade through a
      conventional endotracheal tube is a new alternative for these patients. METHODS:
      A 44-year-old, 133 kg female patient was scheduled to undergo a thoracotomy for
      transthoracic fundoplication. A wire-guided endobronchial blocker (WEB) was
      placed following rapid-sequence induction and intubation with an 8.0 OD single
      lumen endotracheal tube with the aid of a pediatric bronchoscope. RESULTS: The
      WEB, using a guiding loop, was placed with ease and allowed effective one-lung
      ventilation. CONCLUSION: The WEB system allows one-lung ventilation to be
      achieved with a conventional endotracheal tube. The need for reintubation at the
      end of surgery is eliminated and endotracheal tube cross-sectional area is
      conserved.

PMID- 10081547
TI  - Transient radicular irritation after spinal anaesthesia with xylocain.

PMID- 10081548
TI  - Obstetric anaesthesia in Germany.

PMID- 10081549
TI  - Brachial plexus injury during cardiac catheterisation in children.

PMID- 10081550
TI  - 4D-computerized visualisation of human craniofacial skeletal growth and of the
      development of the dentition.
AB  - The understanding of growth and developmental changes can be improved when shapes
      and changes in size, proportion, and relationships are visualized in 3 dimensions
      and at different stages. This applies particularly to craniofacial skeletal
      growth and the development of the dentition. For that purpose 3D-data were
      collected from prenatal human heads ranging from 18 up to 275 mm CRL and from a
      collection of macerated fetal and postnatal skulls. Computer-aided graphical
      reconstructions were obtained from histological serial sections of embryonic and
      early fetal specimens. Proportional changes in the growing skull were recorded by
      means of radiological and cephalometric evaluation. In addition, computed
      tomography was applied to fetal and postnatal skulls. Furthermore, the prenatal
      and postnatal development of the dentition was digitized. To that end 3D-polygone
      sets of these data were read into a workstation computer and animated by means of
      the software Soft Image (Microsoft). This comprehensive 4D insight into growth
      facilitates the understanding and teaching of normal and abnormal development.

PMID- 10081551
TI  - Regulative and adaptive factors in craniofacial growth.
AB  - Generally speaking, the animal experimental models described here are of
      theoretical importance. They fall naturally into the area of formulating general
      trends. Following elucidation of a series of concerns in the future, theoretical
      growth research will be able to provide more directly clinically applicable
      tools. Since no experimental animals of the masticatory type analogous to humans
      exist, results from animal experiments should be considered as statements on the
      biological reactions of analogous biological systems. Last but not least,
      biomechanical model representations point to the growth controlling functions of
      the bony and muscular head system components. These may provide an example for
      the analysis of degenerative changes in other parts of the body and serve as a
      theoretical basis for targeted therapeutic measures.

PMID- 10081552
TI  - Comparison of distal and neutral craniofacial pattern in untreated subjects in
      terms of skeletal harmony and growth.
AB  - Using conventional comparisons of means and multivariate analyses, the aim of
      this study was to establish skeletal proportions and their growth-dependent
      development in untreated subjects with class II/1 malocclusion and compare them
      with a longitudinally-examined, untreated group with neutral occlusion. 138
      untreated children from Nittedal/Norway with an Angle-class II/1 malocclusion
      were examined longitudinally using radiocephalometry at 2 points in time: average
      ages of 9.1 and 12.1 years. These class II/1 children were compared to a group of
      80 untreated children with class I occlusion (also from Nittedal, similar age
      group). In addition to the Norwegian participants, untreated children with class
      II/1 malocclusion from Sweden and Germany were longitudinally analyzed. Besides a
      comparison of the mean values of the measured basal variables, a multivariate
      analysis was conducted with the help of graphically converted regression
      equations (harmony box). In comparison to the class-I children with neutral
      craniofacial pattern, the mandibles in children with class II/1 malocclusion
      showed a significant posterior shift at both points in time. According to
      evaluation with the harmony box, the craniofacial dimensions were harmonious in
      class I occlusion. In all class II/1 groups, the maxilla was located slightly
      disharmoniously to the anterior at both time points. The average basal
      alterations were relatively minor. If not only individual mean values are
      compared with one another, but also multivariate relations of the viscerocranium
      are considered, a maxillary anterior shift is more frequently diagnosed in
      subjects with a class II/1 malocclusion than is possible with a comparison of
      mean values.

PMID- 10081553
TI  - The influence of the muscles of facial expression on the development of the
      midface and the nose in cleft lip and palate patients. A reflection of functional
      anatomy, facial esthetics and physiology of the nose.
AB  - The further improvement of well-established techniques in primary and secondary
      cleft surgery requires a detailed and interdisciplinary knowledge and observation
      of anatomical, functional and developmental problems. An investigation into the
      macroscopic and microscopic anatomy of the perinasal and perioral muscles and
      parts of the human nasal septum, as well as into the pathomorphology of ancient
      skulls with untreated clefts is presented. On this basis an interpretation of
      clinical findings in untreated newborns compared with surgically treated CLP
      patients has been undertaken. The 3D-CT, superimposing photography and coloured
      experimental settings of nasal airflow complete the visualisation of the
      anatomical and functional findings.

PMID- 10081554
TI  - Functional conditions of the mandible: theory and physiology.
AB  - The functional conditions of the mandible are differentiated according to the
      number of kinematic degrees of freedom assigned to each mandibular movement. One
      degree of freedom: pro- and retrusive occlusal border movement. The interplay of
      the TMJs with the occluding teeth determines a compulsory course which
      corresponds to a 4-bar-chain guidance. 2 degrees of freedom: free sagittal mouth
      movement without tooth contact. Using graphic recordings of cyclic mandibular
      movements, the mobile hinge axis is identified as a mandibularly fixed line which
      is not directly categorized as a part of an anatomical structure. In the
      maxillary coordinate system, its movement describes a cylinder; sagittally, it
      describes a circle. The mandibular positions are clearly identifiable with 2
      angles. The in vivo measurements show that neuromuscularly healthy systems supply
      the mandible with anticipatory guidance. 3 degrees of freedom: bolus function.
      The articular space in the TMJ is utilized.

PMID- 10081555
TI  - The temporomandibular joint in video motion--noninvasive image techniques to
      present the functional anatomy.
AB  - The presentation of the functional anatomy of the temporomandibular joint (TMJ)
      is involved with difficulties if dynamic aspects are to be of prime interest, and
      it should be demonstrated with the highest resolution. Usually noninvasive
      techniques like MRI and sonography are available for presenting functionality of
      the temporomandibular joint in video motion. Such images reflect the functional
      anatomy much better than single pictures of figures could do. In combination with
      computer aided records of the condyle movements the video motion of MR and
      sonographical images represent tools for better understanding the relationships
      between functional or dysfunctional patterns and the morphological or
      dysmorphological shape and structure of the temporomandibular joint. The
      possibilities of such tools will be explained and discussed in detail relating,
      in addition, to loading effects caused by transmitted occlusal pressure onto the
      joint compartments. If pressure occurs the condyle slides mainly more or less
      retrocranially whereas the articular disc takes up a more displaced position and
      a deformed shape. In a few extreme cases the disc prolapses out of the joint
      space. These video pictures offer new aspects for the diagnosis of the disc
      condyle stability and can also be used for explicit educational programs on the
      complex dysfunction-dysmorphology-relationship of temporomandibular diseases.

PMID- 10081556
TI  - Masticatory musculature under altered occlusal relationships--a model study with
      experimental animals.
AB  - In a study with experimental animals, the occlusal relationships of male Wistar
      rats were altered by the bilateral extraction of lateral teeth; the bolus
      function was eliminated by feeding a soft diet. Both steps led to relief of
      strain on the temporomandibular joint and thus also in the muscular system
      itself. The masticatory muscles adapted to the new experimental conditions. We
      observed a reduction in muscle dry weight and a shift in muscle fiber composition
      in favour of the IIb fibers, which indicates that less masticatory strength was
      required. Adaptation thus occurred equally on the macroscopic and microscopic
      levels.

PMID- 10081557
TI  - Functional condition of the mandible: physical structures of free mandibular
      movement.
AB  - Starting with the physical definition of the concept "mobile hinge axis", which
      only allows 2 degrees of freedom for planar mandibular movement, it will be shown
      that the hinge axis of the temporomandibular joint cannot be found with a small
      mouth-opening rotation, as is usual but erroneous. By recording cyclic mandibular
      movements with a measuring system which itself possesses 6 degrees of freedom,
      the mobile hinge axis can be found. However, there are patients which do not use
      a mobile hinge axis, which is indicative of latent functional disturbances of the
      neuromuscular system.

PMID- 10081558
TI  - Alteration of the functional condition of the mandible during clinical treatment.
AB  - Free mandibular movements and their neuromuscular guidance were measured with an
      ultrasonic device and analyzed with computer software developed by the authors.
      In all patients examined, we found maxillarly- and mandibularly-fixed axes which
      maintain a constant distance. This guidance system is named a neuromuscularly
      determined dimeric link chain. The position of the mandible is defined by the 2
      rotational angles (mu, alpha) around the axes of the dimeric link chain. This
      dimeric link chain of free movements normally functions according to the
      principle of least action. The angular velocities around the 2 axes show a
      constant ratio during the different segments of motion. In the mu-alpha-diagrams,
      the segments of movements of the mandible are represented by straight lines, the
      shortest path between 2 positions. Individual cases and statistical data show
      that the structure of mandibular movements of patients with skeletal mandibular
      retrognathism combined with dental class-II-relationship without craniomandibular
      pain significantly differs from the structure in patients with neutral alignment.
      Mandibular retrognathism and class-II-relationship are accompanied by marked
      coordination disturbances of rotations around the maxillary and mandibular
      neuromuscular axes. Following orthodontic-surgical treatment that restored ideal
      alignment of the occlusal, articular, and skeletal structures, the patients
      examined showed a similar pattern in the structure of mandibular movements to
      that of patients with neutral skeletal and dental relationships. Thus, combined
      orthodontic-surgical treatment leads to measurable functional harmonization not
      only of the skeletal and dental structures, but also of the neuromuscular
      guidance system.

PMID- 10081559
TI  - Craniomandibular disorders--comparative investigations with clinical examination
      and electronic axiography.
AB  - An essential problem in the diagnosis of craniomandibular disorders is still the
      evaluation of the type and severity of the TMJ diseases. For a differential
      classification of TMJ diseases, we developed an electronic axiography system
      which facilitates a recording of lower jaw movements. It works 3-dimensionally
      and relates to the joints. The measuring system, which was internationally
      patented, is based on a linear resistive foil for the sagittal plane and an
      inductive gauge for the horizontal plane. The aim of this pilot study was to
      evaluate the usefulness of our electronic axiography system in obtaining a
      differential diagnosis of craniomandibular disorders. We examined 30 patients (60
      joints) with complaints in the TMJ area (pain and TMJ sounds). Clinical
      examinations yielded only uncertain indications of TMJ disease. With the help of
      electronic axiography we could differentiate the TMJ diseases into microtrauma
      and macrotrauma. Both forms may show a loss of function and an audible TMJ
      clicking. 23 joints had a macrotrauma (disk displacement with reduction, 20
      times; disk displacement without reduction, 3 times). In 8 joints, a microtrauma
      was found. 3 joints showed a subluxation. In 4 uncertain cases, the diagnosis was
      confirmed with the help of magnetic resonance imaging (MRI). All patients with a
      diagnosed arthrogenic disorder received adequate treatment with reposition
      splints. Our initial results show that 3-dimensional electronic axiography can be
      a good aid in further characterization of craniomandibular disorders and permits
      an effective therapy.

PMID- 10081560
TI  - Biomechanical analysis of stress distribution in the human temporomandibular
      joint.
AB  - The positions of the head of the mandible, of the articular disc and the outline
      of the temporal surface are digitized from sagittal MRI-scans of the
      temporomandibular joint of a 32-year-old subject in 5 different positions of
      occlusion. The stress distribution in the joint is calculated on the basis of
      these data. For each position of the condyle, the momentary center of rotation in
      the head of the mandible and the tangent attached to the temporal surface are
      determined. The line connecting these two points indicates the direction of the
      resulting compressive force. Furthermore, the extension of the area available to
      the force transmission is estimated. By means of these parameters the stress
      distribution is calculated independently from the position. The analyses show
      that the temporomandibular joint is slightly eccentrically loaded in all
      positions. The increase of the stresses is in all cases oriented caudo-ventrally.
      The results are verified in an anatomical specimen of the articular tuberculum.
      The trabecular structures as well as the subchondral bone-lamella of the
      articular tuberculum are functionally adapted to the analyzed stress situations.

PMID- 10081561
TI  - The human temporomandibular joint region in different positions of the mandible.
AB  - The anatomy of the human temporomandibular joint region has been investigated
      mainly under the conditions of dental occlusion. The aim of the present study was
      to elucidate the topographical situations in other functional positions such as
      wide-open mouth, protrusion and lateral displacement. The respective mouth
      positions were adjusted before fixation and controlled by magnetic resonance
      tomography. The temporomandibular joint regions were embedded in epoxy resin, and
      cut serially in the sagittal or the frontal plane. WIDE OPEN MOUTH: The articular
      disc lies with its intermediate zone between the articular tubercle and the
      dorsal convexity of the condylar process, and thus adapts the articulating
      surfaces of the bones perfectly to each other. Massive enlargement of the
      retroarticular cushion is seen, whereas the loss connective tissue on the
      anterior side of the joint appears completely compressed. PROTRUSION: The disc
      lies with its intermediate zone between the convexities of the condylar process
      and the articular eminence. On the lateral side it appears to be compressed
      between mandible and temporal bone. The retroarticular cushion is moderately
      enlarged. The anterior compartment of loose connective tissue is smaller than in
      occlusion. LATERAL DISPLACEMENT: On the working side the articular disc is in a
      stabilized position between the bony joint elements. The balancing condyle is in
      a protruded position with the retroarticular cushion reaching into the dorso
      lateral half of the mandibular fossa. CONCLUSION: Protrusion appears as the
      position with the highest mechanical stress upon the articular disc.

PMID- 10081562
TI  - The function of the disco-muscular apparatus in the human temporomandibular
      joint.
AB  - The morphology and function of the disco-muscular apparatus of the human TMJ is a
      controversial subject. Connections between the muscles which move the mandible
      and the "disco-capsular complex" have been described in a contradictory way. The
      disco-muscular apparatus is also described as being more extensive than that of
      the M. pterygoideus alone to include to the Mm. temporalis and masseter. However,
      the involvement of the latter is considered to be a peripheral variation of the
      normal anatomy and of little, if any, functional significance. The existence of
      independent relationships between the deep portions of the masseter and temporal
      muscles and the disco-capsular apparatus of the human TMJ is rarely discussed or
      explained. The morphologic findings were derived from fixed and unfixed human
      temporomandibular joints (TMJ) of varying ages and both sexes, whereby the
      functional maturity of the masticatory apparatus was taken into consideration.
      The results of the study show that aside from fibers originating from the
      superior venter of the M. pterygoideus lateralis, additional muscle or connective
      tissue fibers from the perimysium of the M. masseter are inserted to varying
      extents into the disc. The same is true for the M. temporalis, which is also
      directly connected to the disc via muscular or fibrous elements, or indirectly
      via fibers from the M. masseter. The insertion of the M. pterygoideus lateralis
      is always in the medial portion of the Discus articularis and those of the Mm.
      temporalis and masseter in the middle and lateral portions of the disc
      respectively. It is highly probable that a direct force transfer through the Mm.
      temporalis and masseter to the articular disc takes place, and that these muscles
      contribute to the movement of the disc during jaw movement, whereas the size and
      form of the muscle insertions are subject to a great deal of individual
      variation.

PMID- 10081563
TI  - Morphometrical examinations of the mandibular ramus for the indication of lag
      screw osteosynthesis described by Eckelt in mandibular condylar fractures.
AB  - For several years, lag screw osteosynthesis as described by ECKELT has been used
      for the surgical treatment of condylar fractures with predominantly positive
      results. However anatomical variations occasionally do not permit the use of the
      lag screw. The aim of the present study was to re-examine the anatomical
      requirements for using ECKELT's lag screw osteosynthesis. Based on a detailed
      structural analysis of 140 isolated cadaver rami mandibulae, it can be seen that
      they principally meet the anatomical requirements for the treatment of mandibular
      condylar fractures with lag screw osteosynthesis using 2.0 mm diameter screws.
      Rare, extreme anatomical variants emphasize the need for a stricter preoperative
      determination of the indications. Using spiral computerized tomography, it is
      possible to exactly assess preoperatively the existing anatomical situation of
      the ascending mandibular ramus on the planned frontal plane of the lag screw.

PMID- 10081564
TI  - Malformations of the temporo-mandibular joint in laboratory animals and in man.
AB  - In 108 fetal mice and 67 rat fetuses the normal development of the
      temporomandibular joint was initially explored. Then malformations of the
      splanchnocranium were induced and studied histologically in 287 newborn rats and
      67 mice. These animals had been delivered by caesarean section after treating the
      pregnant dams with one of 6 different teratogens. Finally, anomalous
      temporomandibular joints in 53 patients were analyzed radiographically and
      compared to the findings made in the above mentioned laboratory animals. Most
      malformations of the temporomandibular region detected were found to be
      embryopathies. They all fit into a new teratogenic order that was established by
      comparing the abnormal to the normal development of the structures involved.

PMID- 10081565
TI  - Influence of craniofacial morphology on primate paranasal pneumatization.
AB  - In order to test the hypothesis that variation in the maxillary sinus volume
      (MSV) of anthropoid primates is related to skull architecture, a mixed sex sample
      of adult primate crania covering Hominoidea, Cercopithecoidea and Ceboidea was
      examined using CT scans. MSV was regressed against basicranial length, using
      reduced major axis analysis. 2 distinct scaling patterns emerged: while a large
      MSV seems to be a primitive condition of Anthropoidea, it is clearly reduced in
      Cercopithecoidea. Although some correlations exist between MSV and different
      indices of the facial skeleton, they are relatively weak and differed among the 3
      groups. A full appreciation of epigenetic factors and the relation of the
      paranasal sinuses to different cranial components is necessary to highlight the
      biological role of skull pneumatization.

PMID- 10081566
TI  - An unusual cavity within the styloid process.
AB  - A rare case of an unusual sinus within the styloid process is described. The
      radiological appearance of this malformation is presented with CT-scans and a
      hypothesis for its development is presented. The malformation is designated as
      "Recessus processus styloidei" and this entity is considered to be a dysgenesis
      of the second branchial arch.

PMID- 10081567
TI  - Functional morphology of the pterygoid hamulus.
AB  - The pterygoid hamulus (PH), a structure on the under surface of the skull base
      which has so far hardly been described, is in a peculiar situation
      biomechanically. The aim of this study is to accumulate sufficient morphological
      data to enable a functional interpretation to be provided. A total of 93 adult
      skulls and 24 children's skulls have been examined, and also an additional 20
      heads in which the relationship to the surrounding muscles could be investigated.
      Measurements were made with a sliding gauge, and sections cut from specimens
      embedded in methyl methacrylate were examined histologically. The hamulus is a
      variable structure which can, however, be allotted to one of a few basic types.
      As nomenclature we suggest the following terms: the base: Basis; body: Corpus,
      sulcus: Sulcus; neck: Collum; head: Caput of the hamulus. The average
      measurements are: length 7.2 mm, sagittal breadth 1.4 mm, transverse breadth 2.3
      mm. The sections show that the medial cortical lamella is thicker than the
      lateral, and that the 2 are bound together by oblique trabeculae. The medial
      gradient angle of the collagen fibers is smaller than that of the lateral. A few
      muscles take origin from the hamulus, the tensor veli palatini turns round the
      neck, and a few of its fibers take origin here. The distribution of the material
      within the hamulus suggests that its body is subjected to greater loading in the
      medio-dorsal direction, but that the head is freely pulled away laterally and
      caudally. Its exposed position at the distal end of the upper dental arch and the
      formation of a bursa or sliding layer in the sulcus suggest that it may be a
      potential source of irritation.

PMID- 10081568
TI  - The significance of the anatomy of the skull base for mechanical modelling: a
      comparative study.
AB  - The present paper aims at analysing the significance of the anatomical structures
      of the human skull base for mechanical modelling. Three different Finite-Element
      (FE)-models of the human neurocranium were developed. The most complex model
      (1242 solid cuboid elements) contains holes and spaces functionally simulating
      the foramina and fissures and additional element layers for the inner relief of
      the skull base (petrous temporal and sella). Of the less complex models, one
      (1256 solid cuboid elements) includes only the 3 cranial fossae, while the other
      (400 solid cuboid elements) represents a rotationally symmetrical ellipsoid with
      a hole for the foramen magnum. Two linear static loadcases, one with a transverse
      loading direction (pressure of 250 kg on the left temporal surface, bearing on
      the right temporal surface) and the other with a sagittal loading direction
      (pressure of 250 kg on the frontal surface, bearing on the occipital surface)
      were computed. The loadcase analyses show, qualitatively and quantitatively,
      similar equivalent von Mises stress values and distributions in the two more
      complex models while the elementary geometric model leads to significantly
      different absolute stress values and distributions. The results of the most
      complex model are highly compatible with experimental observations on transverse
      and sagittal fractures of the skull base.

PMID- 10081569
TI  - 3-dimensional analysis of cleft palate casts.
AB  - It is the aim of presurgical infant orthopedics (PSIO) to reduce the width of the
      cleft and to achieve optimal alignment of the cleft palate segments within the
      first few months of infancy prior to any surgical cleft closure. The question
      about the amount that PSIO can stimulate and steer the growth of the maxilla
      using a Hotz and Gnoinski passive appliance has not yet been satisfactorily
      answered. In this study, a 3-dimensional digital computer-aided procedure was
      developed to analyze metrically and to visualize the growth of the edentulous
      maxilla of cleft lip and palate in infants. In a pilot study, a series of digital
      scans of consecutive plaster casts was carried out. 5 infants with complete
      unilateral cleft lip and palate (UCLP), who had been treated with passive
      appliances were evaluated. Impressions were taken at the age of one week and
      after 3, 6 and 12 months. Following digitizing, the casts were computer
      reconstructed and segmented perpendicular to the alveolar crest, the reference
      points being C1, C1', C2, C2' and I. The volume of the resulting segments was
      ascertained. Computer superimposition of reconstructed consecutive casts was
      employed to facilitate a visualization of the extent and direction of
      morphological changes. Our first results have shown that with our method it is
      possible to quantify the growth rate of defined segments of the maxilla. The 3
      dimensional analysis presented here will be the basis for further studies to
      objectify PSIO.

PMID- 10081570
TI  - Interpretation of the vertical and longitudinal growth of the human skull.
AB  - Our model describes asymptotic growth as a time-dependent process which expresses
      a quantitative change in individual morphological factors. The development and
      growth of the face are intimately connected with the cranial base, which
      undergoes only minor changes between the ages of 0 to 25 years. The difference in
      growth of the neuro- and viscerocranium is evident in that the dimensions and
      angles of the viscerocranium undergo greater changes than those of the
      neurocranium. The anterior cranial base lengthens until the end of normal growth
      via bone apposition at the nasion. This elongates the cranial base. The nasion
      influences the sagittal maxillary relationships. The posterior cranial base shows
      a constant growth rate up to ca. 15 years of age. The face and dentition develop
      along the nasion-gonion and sella-gnathion distance, which demonstrates the
      greatest absolute growth rate. During growth, the viscerocranium increases
      principally in height.

PMID- 10081571
TI  - Complications of local dental anesthesia and anatomical causes.
AB  - Anatomical descriptions usually include only the average topographical
      relationships, but the anatomical structures particularly in the head region
      display great variability. This is one of the essential causes underlying side
      effects and complications of local dental anesthesia. In examinations of
      intravascular needle placement in over 6000 local anesthetic injections in the
      jaws, positive blood aspiration occurred most frequently (5.8%) at the mandibular
      foramen. The close proximity to the cerebral vessels explains the frequency of
      severe side effects. Anatomical studies on the course of the maxillary artery and
      its branches as well as the course of the nerve demonstrate that unexpected
      anatomical constellations can lead to both anesthetic failure and dramatic side
      effects.

PMID- 10081572
TI  - Cheilognathopalatoschisis and its prophylaxis in animal experiments.
AB  - Cheilognathopalatoschisis (cleft lip, -maxilla, and -palate) is the second most
      frequent malformation in humans. The ontogenetic causes are mostly
      multifactorial. Some researchers have succeeded in lowering the frequency of
      occurrence of such clefts in children of predisposed women by giving the latter
      an applied symptomatic replacement therapy with multivitamin preparations or
      other substance classes during early pregnancy. However, the dosage of these
      substances was only anecdotal and their effect unspecific. Many research groups
      world-wide are conducting animal experiments in order to investigate the efficacy
      of vitamins and other substances as prophylactics. The experiments are usually
      conducted with laboratory rats and mice, and clefts are often induced by applying
      chemical noxa. The results of these trials, however, are controversial. Where
      some authors were able to prove protective effects of the vitamins or other
      substances they employed, others found evidence that such replacement therapy has
      no prophylactic effect. This paper provides insight into such studies with
      experimental animals, and compares their results.

PMID- 10081573
TI  - Disturbances of palatogenesis and their prophylaxis in animal experiments.
AB  - The goal of this study using experimental animals was to induce disturbances of
      palatogenesis which are comparable to human maxillary clefts. Simultaneously, an
      in vivo method of testing presumed antiteratogenic substances is presented. 13
      gravid Wistar rats bearing 98 fetuses received 200 mg/kg of procarbazine on day
      14 post conception (p. c.) to induce malformations. 7 of these gravid animals,
      bearing 48 fetuses, additionally received 200 mg/kg thiamine daily from day 13-19
      p. c. to prevent malformations. On day 20 p. c., the fetuses were teratologically
      screened: all fetuses were externally examined, the skeletons of 1/3 were
      visualized using cartilage/bone staining methods, and the heads of 2/3 were
      histologically examined in 24 sequential frontal sections. At birth, the
      procarbazine-damaged fetuses exhibited a high rate of cleft palate, primarily
      involving the secondary palate (94%), which was accompanied by retardation and
      delayed ossification of the viscerocranium. 66% of the fetuses showed pronounced
      brachygenia. The disturbances of palatogenesis were frequently accompanied by
      disturbed odontogenesis, which chiefly manifested itself near the cleft of the
      frontal maxilla as a reduction in size (63%), retardation (38%) or absence (31%)
      of the tooth germ. In the trial group additionally treated with thiamine, the
      findings did not differ significantly from these. The animal model presented here
      proved suitable for studying palatogenesis and localization-specific testing of
      substances presumed to have antiteratogenic effects. A prophylactic effect of
      thiamine initially tested as a highly-dosed monotherapy was not verifiable.

PMID- 10081574
TI  - Expression patterns of complex glycoconjugates and endogenous lectins during
      fetal development of the viscerocranium.
AB  - Experimental evidence suggests that carbohydrates and their corresponding
      receptors (endogenous lectins) decode biological information. Therefore, the
      expression of complex oligosaccharides--the potential ligand part of this
      recognition system--during chondrogenesis and osteogenesis was determined in the
      viscerocranium of fetal rats by mapping the staining patterns of exogenous
      lectins. Results were compared with the expression of bone- and/or cartilage
      specific core proteins and the binding profiles of neoglycoconjugates. These
      synthetic tools make possible the localization of sugar-ligand-binding sites. The
      spatial and temporal distribution patterns of glycoconjugates were highly dynamic
      and demonstrated a clear correlation with characteristic morphological
      modifications. The glycobiological characterization of precartilage mesenchymal
      cells revealed distinct differences compared to prospective bone anlagen.
      Especially the binding of the exogenous lectin from Griffonia simplicifolia II,
      that selectively visualized prechondral aggregations, reveals that regulation of
      early chondral growth is at least phenomenologically correlated with a relatively
      atypical oligosaccharide composition terminating with N-acetylglucosamine.

PMID- 10081575
TI  - The pathology of the velopharyngeal musculature in cleft palates.
AB  - AIMS: This article draws attention to a pathological finding in the cleft palate
      condition that has not been previously described: It is demonstrated that the
      palatal aponeurosis exists even in cleft palates, but it is disrupted,
      malpositioned and folded in 2 layers. It is possible to dissect the 2 layers and
      to unfold the aponeurosis to form a tough tendinous plane. Thus, the
      retropositioning of the levator veli palatini muscle sling is facilitated.
      CONCLUSION: For a normal reconstruction of the cleft palate it is not only
      necessary to reconstruct the levator veli palatini muscle sling but also to
      approximate and to suture the fibres of the palatal aponeurosis to the
      corresponding fibres of the opposite side after unfolding them in a mediodorso
      cranial direction. In this manner a continuous palatal aponeurosis can be created
      and subsequently it can serve as a transmitter of the muscle forces.

PMID- 10081576
TI  - Normalization of keratinocyte-type integrins during the establishment of the oral
      mucosa phenotype in vitro.
AB  - In stratified epithelia, integrins play a fundamental role in mediating basal
      cell attachment to a variety of extracellular matrix molecules. To assess whether
      keratinocyte-specific integrins are expressed in a similar way as in the normal
      situation also under in vivo related conditions, we processed oral mucosa
      equivalents consisting of keratinocytes and fibroblasts from non-cornified
      gingiva. In this model histomorphology, the expression of differentiation
      specific keratins and keratinocyte-type integrins exhibited similarity to the
      tissue of origin. The stages of tissue normalization were assessed on frozen
      sections by indirect immunofluorescence. The initial activated stage (1 week) was
      characterized by (i) incomplete epithelial organization and a weak presence of
      the suprabasal mucosa type keratin K4, (ii) diffuse expression of the integrin
      chains beta 1 and alpha 6 and (iii) abundance of the wound healing-associated
      integrin alpha v throughout the whole epithelium. After 2 weeks, the increase in
      epithelial organization was characterized by (i) the presence of a basal and
      suprabasal cell compartment, (ii) extension of K4 in the suprabasal compartment,
      (iii) extended expression of the keratinocyte integrins beta 1 and alpha 6 and
      (iv) concentration of alpha v integrin underneath basal cells. Further
      normalization of tissue architecture was indicated by (i) a slight increase in K4
      extension, (ii) appearance of keratinocyte integrins beta 1 and alpha 6 in basal
      and parabasal cells and (iii) interruption of the band-like alpha v integrin
      immunolocalization at the subepithelial site. The findings in the in vitro model
      system indicate that these oral mucosa equivalents exhibit similarities to the in
      vivo situation of non-cornified gingiva, thus rendering them a suitable model for
      the assessment of stages during epithelial reconstruction or in vivo relevant
      studies on material effects.

PMID- 10081577
TI  - The granulated convoluted tubules of the rat submandibular glands under
      experimental conditions.
AB  - Granulated convoluted tubules are the specific ductal segment of the
      submandibular glands of mice and rats. These tubules are functionally integrated
      into hormonal circuits, produce regulatory peptides as well as epidermal and
      nerve growth factor. The experimental studies on adult male Wistar and Fischer
      344 rats demonstrate acute cytotoxic lesions of the granulated tubules by means
      of a single dose of 2-acetylaminofluorene. After only a few administrations of
      the compound the intralobular duct tree is lined by an atrophic epithelium with
      loss of specific structures, the EGF immunoreactivity and the susceptibility to
      further cytolethal effects. The early selective damage of the granulated
      convoluted tubules indicates that the growth factor production and certain drug
      metabolizing/drug-excreting capacities are situated within the same ductal
      segment. It is considered that other systemically administered compounds might
      also influence this growth factor-producing ductal segment, though less
      dramatically than 2-acetylaminofluorene.

PMID- 10081578
TI  - Dentin dysplasia type I--a case report.
AB  - A case report on dentin dysplasia type I, a congenital disease (autosomal
      dominant gene defect) affecting deciduous and permanent teeth, is depicted
      including representations of clinical and histological features, X-ray and CT
      findings. Therapy includes extraction of all teeth, ectomization of cystic
      alteration, revision of paranasal sinus. Aesthetic and functional rehabilitation
      by means of insertion of a complete denture was achieved.

PMID- 10081579
TI  - Molecular bases of epithelial cell invasion by Shigella flexneri.
AB  - The pathogenesis of shigellosis is characterized by the capacity of the causative
      microorganism, Shigella, to invade the epithelial cells that compose the mucosal
      surface of the colon in humans. The invasive process encompasses several steps
      which can be summarized as follows: entry of bacteria into epithelial cells
      involves signalling pathways that elicit a macropinocitic event. Upon contact
      with the cell surface, S. flexneri activates a Mxi/Spa secretory apparatus
      encoded by two operons comprising about 25 genes located on a large virulence
      plasmid of 220 kb. Through this specialized secretory apparatus, Ipa invasins are
      secreted, two of which (IpaB, 62 kDa and IpaC, 42 kDa) form a complex which is
      itself able to activate entry via its interaction with the host cell membrane.
      Interaction of this molecular complex with the cell surface elicits major
      rearrangements of the host cell cytoskeleton, essentially the polymerization of
      actin filaments that form bundles supporting the membrane projections which
      achieve bacterial entry. Active recruitment of the protooncogene pp 60c-src has
      been demonstrated at the entry site with consequent phosphorylation of cortactin.
      Also, the small GTPase Rho is controlling the cascade of signals that allows
      elongation of actin filaments from initial nucleation foci underneath the cell
      membrane. The regulatory signals involved as well as the proteins recruited
      indicate that Shigella induces the formation of an adherence plaque at the cell
      surface in order to achieve entry. Once intracellular, the bacterium lyses its
      phagocytic vacuole, escapes into the cytoplasm and starts moving the inducing
      polar, directed polymerization of actin on its surface, due to the expression of
      IcsA, a 120 kDa outer membrane protein, which is localized at one pole of the
      microorganism, following cleavage by SopA, a plasmid-encoded surface protease. In
      the context of polarized epithelial cells, bacteria then reach the intermediate
      junction and engage their components, particularly the cadherins, to form a
      protrusion which is actively internalized by the adjacent cell. Bacteria then
      lyse the two membranes, reach the cytoplasmic compartment again, and resume actin
      driven movement.

PMID- 10081580
TI  - Quorum sensing and the cell-cell communication dependent regulation of gene
      expression in pathogenic and non-pathogenic bacteria.
AB  - Although it has been clear for some time that individual bacterial cells employ
      intra-cellular signalling systems to sense, integrate and process information
      from their surroundings, their widespread capacity to perceive information from
      other bacterial cells is only just beginning to be recognised. Recent work has
      established that diverse bacteria exploit a cell-cell communication device to
      regulate the transcription of multiple target genes. This communication device
      termed 'quorum sensing', depends on the production of one or more diffusible
      signal molecules termed 'autoinducers' or 'pheromones' which enable a bacterium
      to monitor its own cell population density. Quorum sensing is thus an example of
      multicellular behaviour in prokaryotes and regulates diverse physiological
      processes including bioluminescence, swarming, antibiotic biosynthesis, plasmid
      conjugal transfer and the production of virulence determinants in animal, fish
      and plant pathogens. In Gram-negative bacteria, the best understood family of
      signal molecules are the N-acylhomoserine lactones (AHLs) which vary
      predominantly in the presence or absence of an acyl chain C3 substituent (oxo- or
      hydroxy-) and length of the N-acyl side chain. However not all quorum sensing
      signal molecules are AHLs; in Gram-positive bacteria, they are often post
      translationally modified peptides. Irrespective of the chemical 'language'
      employed, interference with either the synthesis or transmission of a quorum
      sensing signal molecule in pathogenic bacteria offers an exciting new strategy
      for controlling infection.

PMID- 10081581
TI  - Current topics in signal transduction in bacteria.
AB  - Among the signal transfer systems in bacteria two types predominate: two
      component regulatory systems and quorum sensing systems. Both types of system can
      mediate signal transfer across the bacterial cell envelope; however, the
      signalling molecule typically is not taken up into the cells in the former type
      of system, whereas it usually is in the latter. The Two-component systems include
      the recently described (eukaryotic) phosphorelay systems; quorum sensing systems
      can be based upon autoinducers of the N-acylated homoserine lactones, and on
      autoinducers of a peptidic nature. A single bacterial cell contains many
      signalling modules that primarily operate in parallel. This may give rise to
      neural-network behaviour. Recently, however, for both types of basic signal
      transfer modules, it has been demonstrated that they also can be organised in
      series (i.e. in a hierarchical order). Besides their hierarchical position in the
      signal transduction network of the cell, the spatial distribution of individual
      signalling modules may also be an important factor in their efficiency in signal
      transfer. Many challenges lie hidden in future work to understand these signal
      transfer processes in more detail. These are discussed here, with emphasis on the
      mutual interactions between different signal transfer processes. Successful
      contributions to this work will require rigorous mathematical modelling of the
      performance of signal transduction components, and -networks, as well as studies
      on light-sensing signal transduction systems, because of the unsurpassed time
      resolution obtainable in those latter systems, the opportunity to apply repeated
      reproducible stimuli, etc. The increased understanding of bacterial behaviour
      that already has resulted--and may further result--from these studies, can be
      used to fine-tune the beneficial activities of bacteria and/or more efficiently
      inhibit their deleterious ones.

PMID- 10081582
TI  - Dipodascus capitatus, Dipodascus spicifer and Geotrichum clavatum: genomic
      characterization.
AB  - The G + C contents of 25 strains of Dipodascus capitatus, Dipodascus spicifer and
      Geotrichum clavatum were found to be heterogeneous on basis of derivative graphs
      of the melting profiles. Strains showing similar derivative graphs of the melting
      curve exhibited high levels of DNA homology (80-100%); strains showing dissimilar
      derivative graphs exhibited low levels of DNA homology (5 to 45%). Being
      considered separate taxa on basis of these parameters, D. capitatus, D. spicifer
      and G. clavatum could be identified by a combination of the key characteristics
      growth on xylose, cellobiose, salicin and arbutin.

PMID- 10081583
TI  - Candida arabinofermentans, a new L-arabinose fermenting yeast.
AB  - Candida arabinofermentans (type strain NRRL YB-2248, CBS 8468), a new yeast that
      ferments the pentose L-arabinose, is described. The three known strains of this
      new species were isolated from insect frass of pine and larch trees in the U.S.
      Phylogenetic analysis of nucleotide sequences from the D1/D2 domain of large
      subunit (26S) ribosomal DNA places C. arabinofermentans among the methanol
      assimilating yeasts and most closely related to Candida ovalis. Strains of the
      new species produce 0.7-1.9 g/l ethanol from L-arabinose.

PMID- 10081584
TI  - Coproporphyrin excretion by Azorhizobium caulinodans under micro-aerobic
      conditions.
AB  - Azorhizobium caulinodans ORS571 was found to excrete moderate amounts of a
      fluorescent pigment into the culture medium in response to dissolved oxygen
      tensions below 1.0 kPa. The pigment was identified as coproporphyrin, on the
      basis of its optical and fluorescence spectra. FixLJ and fixK mutant derivatives
      of ORS571 were found to excrete 25-fold higher amounts of coproporphyrin under
      micro-aerobic conditions than the wild type strain. These observations suggest
      that A. caulinodans switches from an aerobic to an anaerobic coproporphyrinogen
      oxidase when the dissolved oxygen tension falls below 1.0 kPa and that the fixLJ
      and fixK genes are involved in the regulation of expression of the anaerobic
      coproporphyrinogen oxidase.

PMID- 10081585
TI  - Physiological characterisation of a pyruvate-carboxylase-negative Saccharomyces
      cerevisiae mutant in batch and chemostat cultures.
AB  - A prototrophic pyruvate-carboxylase-negative (Pyc-) mutant was constructed by
      deleting the PYC1 and PYC2 genes in a CEN.PK strain of Saccharomyces cerevisiae.
      Its maximum specific growth rate on ethanol was identical to that of the isogenic
      wild type but it was unable to grow in batch cultures in glucose-ammonia media.
      Consistent with earlier reports, growth on glucose could be restored by supplying
      aspartate as a sole nitrogen source. Ethanol could not replace aspartate as a
      source of oxaloacetate in batch cultures. To investigate whether alleviation of
      glucose repression allowed expression of alternative pathways for oxaloacetate
      synthesis, the Pyc- strain and an isogenic wild-type strain were grown in aerobic
      carbon-limited chemostat cultures at a dilution rate of 0.10 h-1 on mixtures of
      glucose and ethanol. In such mixed-substrate chemostat cultures of the Pyc-
      strain, steady-state growth could only be obtained when ethanol contributed 30%
      or more of the substrate carbon in the feed. Attempts to further decrease the
      ethanol content of the feed invariably resulted in washout. In Pyc- as well as in
      wild-type cultures, levels of isocitrate lyase, malate synthase and phospho-enol
      pyruvate carboxykinase in cell extracts decreased with a decreasing ethanol
      content in the feed. Nevertheless, at the lowest ethanol fraction that supported
      growth of the Pyc- mutant, activities of the glyoxylate cycle enzymes in cell
      extracts were still sufficient to meet the requirement for C4-compounds in
      biomass synthesis. This suggests that factors other than glucose repression of
      alternative routes for oxaloacetate synthesis prevent growth of Pyc- mutants on
      glucose.

PMID- 10081586
TI  - Validation of the basidiomycetous yeast, Sporidiobolus microsporus sp. nov.,
      based on phenotypic and molecular analyses.
AB  - The validation of Sporidiobolus microsporus Higham, nom. nud. is based on
      phenotypic characterization and molecular sequence analysis of a partial region
      of the large sub-unit ribosomal DNA. The species is compared, based on phenotypic
      and molecular characteristics, with other species of Sporidiobolus and the
      closely related Rhodosporidium fluviale.

PMID- 10081587
TI  - Temperature and NaCl-tolerance of rock-inhabiting meristematic fungi.
AB  - Black meristematic fungi together with lichens and cyanobacteria dominate the
      micro-flora of rock surfaces in arid and semi-arid environments of hot and cold
      deserts. This study shows that rock inhabiting meristematic fungi are extremely
      tolerant against high temperatures, desiccation and osmotic stress. Their
      temperature tolerance increases with increasing dehydration of the fungal
      thallus. Air dried mycelia of black yeasts stand temperatures up to 120 degrees C
      for at least 0.5 hours. As response to high temperatures multilayered cell walls
      are developed and trehalose is accumulated whereas the intracellular glycerol
      regulates the osmotic potential under NaCl stress. Strains from rock in moderate
      climate (North Germany) show the same tolerance than those isolated from the
      Mediterranean area. Hortaea werneckii--hitherto only described as agent of human
      Tinea nigra--is shown to be the most tolerant rock inhabiting species tested.
      Meristematic fungi cannot be pre-adapted to higher growth temperatures by
      increased incubation temperatures. Considering the results of this study the
      justification of the term 'stress' is discussed with regard to rock inhabiting
      fungi and their natural environment. Consequences for conservation treatments of
      monuments decayed by meristematic fungi are discussed on the basis of the
      ecophysiological properties of the fungi.

PMID- 10081588
TI  - Diversity and affinities among species and strains of Lipomyces.
AB  - Phylogenetic relationships of the yeast genus Lipomyces were studied using
      sequences from fragments of 5.8S rRNA gene and from internal transcribed spacer
      region ITS2 of 13 strains (7 type strains included) representing five species and
      subtaxa, and originating from different geographical locations (Japan, Trinidad,
      Nigeria, North America, Western Europe, Russia, South Africa, Mauritius).
      Parsimony and distance analyses were performed. Tree topology from the parsimony
      and distance analyses of the sequence confirmed the results of nDNA
      reassociation. Results segregate the 13 isolates of Lipomyces into five major
      clades.

PMID- 10081589
TI  - Osteogenesis mechanism based on kinetic theory.
AB  - In our earlier studies, we considered osteogenesis to be a nucleation mechanism
      accompanied by preliminary diffusion and showed the optimum mechanical conditions
      for promoting this ionic diffusion. In this study, we performed an analysis of
      the nucleation mechanism of hydroxyapatite (HA) in areas with a high
      concentration of transported Ca and PO4 ions in the pore region along the
      collagen alignment. We derived the equation of the HA nucleation rate as a
      function of hydrostatic tensile stress, sigma P and surface energy change (gamma
      lambda), where gamma is the surface energy of the HA particle and lambda is the
      decreasing factor of gamma during HA nucleation. lambda is thus related to the
      effect of chemical and electric stimulations. Finally, we formulated a unified
      equation of the nucleation rate of HA, which consists of ionic diffusion and HA
      nucleation processes.

PMID- 10081590
TI  - Contact stress at articular surfaces in total joint replacements. Part II:
      Analytical and numerical methods.
AB  - In this second part of the series of reviews, attention focuses on analytical and
      numerical methods that have been used to estimate the magnitude of the contact
      stress in: models of articular joints; models of total joint replacements,
      without and with the associated joint; or models of simple physical systems that
      are deemed to have relevance to conditions at articular surfaces in
      arthroplasties. Three main recommendations emerge from this review. First,
      analytical methods should be avoided. Second, for numerical studies, the
      nonlinear contact finite element method should be used. Third, more work is
      needed in many areas, an example of which is the effect of the method of
      sterilization of tibial inserts on the estimated contact stress at the
      tibiofemoral interface in knee implants.

PMID- 10081591
TI  - Comparative study of the sorption of clomipramine and viloxazine hydrochlorides
      in Stedim 6 and PVC bags.
AB  - The stability of two antidepressant drugs, clomipramine and viloxazine
      hydrochlorides, was studied as was their possible sorption on Stedim 6, a new
      multilayer polyethylene-lined film, which was considered comparatively to
      polyvinyl chloride (PVC) and glass surfaces. Appropriate amounts of the drugs
      were added to 500 ml of 5% dextrose and 0.9% sodium chloride solutions in Stedim
      6 and PVC bags, and in glass flasks, in order to obtain the concentrations
      currently used in clinical practice. All the containers were stored at room
      temperature in daylight for 72 hours. Samples were taken at various times and
      evaluated for remaining drug concentrations by UV spectrometry. The two drugs
      appeared stable under the given conditions. No concentration decrease was
      observed in glass flasks. Viloxazine hydrochloride showed an excellent
      compatibility with the PVC bags, but a slight concentration decrease (about 6-7%
      in 72 hours) was observed for clomipramine hydrochloride, depending on the
      contact duration. The compatibility of the two drugs with the new material Stedim
      6 was found to be perfect. The behavioral differences observed between the two
      drugs with regard to PVC are explained in terms of differences of lipophilicity
      of the drugs. Those observed for a given drug with regard to the two materials
      are due to the crystalline structure of polyethylene and the amorphous one of
      PVC.

PMID- 10081592
TI  - A methodology for examining the plausibility of accelerated aging protocols for
      UHMWPE components.
AB  - In light of the time-intensive nature of using real-time shelf-aged specimens in
      research into property changes of ultra-high-molecular-weight polyethylene
      (UHMWPE), accelerated thermal diffusion oxidative aging (usually referred to as
      accelerated aging) is frequently resorted to. A number of such aging protocols
      have been reported in the literature, with various claims for their producing
      changes in the properties of the polymer being the same as or similar to those
      seen in real-time shelf-aged samples. The thrust of the present work is the
      presentation of a methodology for examining such claims. The methodology is
      applied to six properties (% crystallinity, melting temperature, oxidation index,
      ultimate tensile strength, ultimate tensile elongation, and tensile toughness) of
      4150HP UHMWPE grade, sterilized using six different methods, prior to and
      following the use of a specific accelerated aging protocol (oxygen gas at 70
      degrees C and 507 kPa pressure; 14 d.). These six properties have been identified
      in the literature as being strongly correlated with the clinical wear of UHMWPE
      articular components. It is shown that the claim for the protocol used in the
      present work (in terms of the simulated equivalent shelf aging time) is
      plausible. It needs to be emphasized, however, that this conclusion is tentative
      given the paucity of the relevant literature results that are currently available
      and which are vital to the application of the methodology.

PMID- 10081593
TI  - Platelet and cell interactions on gold sputter-deposited polymeric surfaces.
AB  - Surface treatment as gold sputter-deposited treatment onto various polymeric
      surfaces has been investigated to improve the cell-, tissue- and blood
      compatibility. Surface treated samples were characterized by measurement of
      contact angle goniometer and electron spectroscopy for chemical analysis (ESCA).
      The contact angles on the gold-coated polymeric surfaces decreased from 95-65
      degrees to around 50 degrees, i.e., increased hydrophilicity due to incorporation
      of gold thin layer. From the results of ESCA analysis of the modified polymeric
      surfaces, surface modification by the gold-sputter method was successfully
      performed. Morphology of the adhered platelets on the gold-coated polymeric
      surfaces showed lesser activating than control, and the number of adhered
      platelets surface modified samples decreased with decreasing water contact angle.
      Fibroblast cell adhesion and growth on the gold-coated polymeric surfaces were
      more active than those of control. It seems that surface wettability and surface
      chemistry of gold play important roles for platelet adhesion and cell adhesion,
      spreading and growth.

PMID- 10081594
TI  - Human marrow cells-derived cultured bone in porous ceramics.
AB  - From four patients (mean age, 60 years; range 51-76 years), 3 ml of bone marrow
      was collected from the ilium. The marrow was cultured to concentrate and expand
      the marrow mesenchymal cells on a culture dish. The cultured cells were then
      subcultured either on another culture dish or in porous areas of hydroxyapatite
      ceramics in the presence of dexamethasone and beta-glycerophosphate (osteogenic
      medium). The subcultured tissues on the dishes were analyzed by scanning electron
      microscopy (SEM), and subcultured tissues in the ceramics were implanted
      intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells
      and a marked formation of bone matrix beneath the cell layers was observed on the
      subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured
      tissues revealed thick layer of lamellar bone together with active osteoblasts
      lining in many pore areas of the ceramics after 2 months. The in vitro bone
      formation on the culture dishes and in vivo bone formation in porous ceramics
      were detected in all cases. These results indicate that we can assemble an in
      vitro bone/ceramic construct, and due to the porous framework of the ceramic, the
      construct has osteogenic potential similar to that of autologous cancellous bone.
      A significant benefit of this method is that the construct can be made with only
      a small amount of aspirated marrow cells from aged patients with little host
      morbidity.

PMID- 10081595
TI  - Varying the mechanical properties of bone tissue by changing the amount of its
      structurally effective bone mineral content.
AB  - The effect of fluoride ions on the mechanical properties of bone tissue in
      tension was investigated with an in vitro model. Structurally effective Bone
      Mineral Content (BMC) of bovine bone tissue was changed by fluoride ion
      treatment. First, bovine cortical bone specimens were treated with a detergent
      solution in order to increase the diffusion rates of the treatment ions across
      the samples. After the initial treatment, different ion solutions were used to
      treat the tension samples (fluoride, sodium and chloride). Ionic strength and pH
      were varied. Experimental results showed that the sodium chloride solutions of
      different ionic strengths, at physiological and high pH, do not affect the
      mechanical properties of bone tissue in tension. However, uniform fluoride
      treatment across the samples reduced the mechanical strength of bone tissue by
      converting small amounts of bone mineral to mostly calcium fluoride. This action
      reduces the structurally effective BMC and also possibly effects the interface
      bonding between the bone mineral and the organic matrix of the bone tissue.

PMID- 10081596
TI  - Improvement of the friction behaviour of NiTi orthodontic archwires by nitrogen
      diffusion.
AB  - The lack of low friction coefficient for the NiTi superelastic archwires makes
      difficult the optimal use of these materials in orthodontic applications. In this
      study, the decrease of this friction coefficient has been achieved by means of
      nitrogen diffusion heat treatments. The titanium nitride coating has been
      characterised by means of optical and scanning electron microscopy.
      Transformation temperatures, critical stresses, hardness and friction coefficient
      have been determined. Besides, the metallic ion release studies showed that the
      titanium nitride coating prevents biodegradation.

PMID- 10081597
TI  - Adaptive Morse code recognition using variable degree variable step size LMS for
      persons with disabilities.
AB  - In this paper, we applied variable degree, variable step size LMS algorithm to
      adaptive Morse code recognition for persons with impaired hand coordination and
      dexterity. The automatic recognition of Morse code by the disabled is difficult
      because they cannot maintain a stable typing rate. Therefore, a suitable adaptive
      automatic recognition method is needed. In this adaptive Morse code recognition
      method, three processes are involved: character separation, character
      recognition, and adaptive processing. Statistical analyses demonstrated that the
      proposed method resulted in a better recognition rate compared to alternative
      methods from the literature.

PMID- 10081598
TI  - Recovery from mild head injury.
AB  - The subjective and objective sequelae accompanying mild head injury (MHI) are
      discussed in an attempt to clarify MHI's immediate and long-term consequences.
      Areas covered included epidemiology, classification, the post-concussive syndrome
      (PCS), malingering, extent of recovery, rehabilitation and guidelines for
      clinical practice. Special emphasis is placed on the poor relationship between
      subjective complaint and objective measures of impairment. Also discussed are
      some of the methodological problems in the MHI literature, including attempts to
      match MHI subjects and controls with respect to cognitive and emotional complaint
      and the possible confounding effects of practice. The evidence for long-lasting
      (i.e. more than 1 year), subtle neurobehavioral impairment after MHI indicates
      that additional research is required on MHI 1 year or more after injury.

PMID- 10081599
TI  - Epidemiology and predictors of post-concussive syndrome after minor head injury
      in an emergency population.
AB  - OBJECTIVE: To determine if clinical variables or neurobehavioural test (NBT)
      scores obtained in the ED within 24 hours of minor head injury (MHI) predict the
      development of postconcussive syndrome (PCS). METHODS: Prospective, observational
      study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of
      consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new
      neurologic focality on PE, and no brain injury on CT (if done). All patients
      received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3
      and 6 months to determine if patients met the DSM IV definition of PCS. ANALYSIS:
      Stepwise, multivariate, logistic regression. RESULTS: Predictors of PCS at 1
      month were female gender (OR = 7.8; 95% CI = 41.6, 1.98), presence of both
      retrograde and anterograde amnesia (OR = 0.055; CI = 0.002, 0.47), Digit Span
      Forward Scores (OR = 0.748; CI = 0.52, 1.03) and Hopkins Verbal Learning A scores
      (OR = 0.786; CI = 0.65, 0.91); at 3 months, presence of both retrograde and
      anterograde amnesia (OR = 0.13; CI = 0.0, 0.93), Digit Span Forward Scores (OR =
      0.744; CI = 0.58, 0.94). No variables fit the model at 6 months. 92% of males
      scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of
      females scoring < 9 on Digit Span Forward did have PCS at 1 month. CONCLUSIONS:
      Gender and two NBTs can help predict PCS after MHI.

PMID- 10081600
TI  - Intonation unit analysis of conversational discourse in closed head injury.
AB  - This study employed a modification of the intonation unit analysis for
      conversational discourse developed by Mentis and Prutting. The percentage of
      total intonation units produced within separate ideational categories was
      calculated for groups of closed head-injured and normal control subjects as well
      as the examiner. No significant differences were found between subject groups or
      the examiner's performance within the two groups. However, significant
      differences were noted between the examiner's production of intonation units and
      the performances of both subject groups. Findings suggest the manner in which
      samples of conversation were elicited may have constrained the context, thereby
      masking potential differences between groups.

PMID- 10081601
TI  - Epileptic falling spells after epidural haematoma in adult Down's syndrome.
AB  - A 35-year-old man with Down's syndrome showed epileptic falling spells. He had
      suffered from a traumatic right-sided epidural haematoma 3 years before. It had
      been neurosurgically treated, but MRI taken 5 days later had revealed a small
      contracoup contusion at the left temporal lobe. His falling spell was a brief
      tonic seizure without disturbance of consciousness. Background activities of EEG
      consisted of slow alpha waves interspersed with sporadic theta waves and the
      amplitude at the left temporal area was lower than the opposite one. Interictal
      EEG showed sharp waves or sharp and slow wave complexes predominantly at the
      right temporo-centro-parietal area as well as diffuse, though predominantly at
      frontal areas, bursts of slow waves with high amplitude. The EEG suggested focal
      epileptic activities evolving into secondary generalization. SPECT of the brain
      showed the hypoperfusion at the left temporal area and at the right
      posterotemporo-parietal area, where the hypoperfusion was somewhat reduced after
      the improvement of seizures. Seizures were well controlled with phenytoin
      combined with phenobarbital. The incidence of epilepsy in the Down's syndrome has
      been reported to increase after the middle age in association with the
      development of Alzheimer's neuropathology. When those people would sustain head
      injuries, it was necessary to follow carefully using SPECT and EEG.

PMID- 10081602
TI  - A case of amnestic syndrome caused by a subcortical haematoma in the right
      occipital lobe.
AB  - A case of an amnestic syndrome caused by a subcortical haematoma in the right
      occipital lobe is reported. A 62-year-old right-handed man presented with a
      sudden onset of headache to the hospital. On admission, he had a left homonymous
      hemianopsia, disorientation and recent memory disturbance, but had normal remote
      memory and digit span. Computed tomography (CT) and magnetic resonance imaging
      (MRI) revealed a subcortical haematoma in the right occipital lobe. These
      findings suggest that the patient's amnesia was caused by a lesion of the
      retrosplenial region in the non-dominant hemisphere.

PMID- 10081603
TI  - Modulation of formalin-evoked hyperalgesia by intrathecal N-type Ca channel and
      protein kinase C inhibitor in the rat.
AB  - 1. omega-CgTx attenuated formalin-evoked biphasic flinches, while PKC inhibitor
      (STU) attenuated phase 2 and was reversed by PDBu. 2. omega-CgTx and STU
      suppressed the increase in CSF-glutamate after formalin injection. 3. Morphine
      completely suppressed both increased flinching and CSF glutamate release. 4.
      Thus, omega-CgTx (N-type Ca channels) may regulate neurotransmitter release
      evoked by C fiber activation and the formalin-evoked hyperalgesia may possibly be
      provoked as a result of PKC activation elicited by both presynaptic
      neurotransmitter release and activation of NMDA receptors in the spinal neurons.

PMID- 10081604
TI  - Hypothermia prevents biphasic glutamate release and corresponding neuronal
      degeneration after transient spinal cord ischemia in the rat.
AB  - 1. Spinal cord ischemia evoked a biphasic increase in CSF-Glu during 20 min of
      ischemia (40%) and at 2 hr after reperfusion (70%) in the nontreated group that
      was attenuated by all treated groups. But MK-801 (15 micrograms i.t.) did not
      affect the increased Glu at 2 hr (80%). 2. The argyrophilia observed in laminae
      II-V at 8 hr after reperfusion was attenuated by hypothermia (33 degrees C) and
      combination with MK-801, but the attenuation was less with MK-801. 3. Mild
      hypothermia attenuated the biphasic increase in CSF-Glu and corresponding
      development of neuronal damage after spinal cord ischemia. 4. Mild hypothermia
      with NMDA antagonism did not yield any further effects, suggesting that
      hypothermia itself plays a pivotal role in the protection.

PMID- 10081605
TI  - Novel neuronal effects of midkine on embryonic cerebellar neurons examined using
      a defined culture system.
AB  - 1. Midkine (MK) is known to be a member of a family of heparin-binding
      neurotrophic factors. We used a chemically defined culture system to examine
      neuronal activities of MK on embryonic rat cerebellar cells. 2. In the culture
      system, a substrate surface was chemically modified either with amine or with
      laminin peptide to homogenize substrate conditions for culturing neurons. 3. At
      the optimal concentration (2.5 ng/ml), MK moderately promoted survivability (1.3
      fold) and accelerated neurite outgrowth (1.4-fold) of cerebellar cells,
      putatively granule neurons, grown on an amine-modified surface. 4. Higher dosages
      (10 ng/ml or more) of MK, however, caused cellular fragmentation and detachment.
      Such degenerative effects were diminished by increasing the surface adhesiveness
      using laminin peptide, suggesting that the cellular degeneration might be caused
      by changes in the adhesive property of the neuron. 5. Using this culture system,
      we have found that MK has a novel modulatory activity of neuronal adhesiveness on
      the cultured cerebellar granule cells. Together with the expression pattern of
      MK, our study supports the idea that MK may be involved in the developmental
      events of the cerebellum.

PMID- 10081606
TI  - The order of exposure of tau to signal transduction kinases alters the generation
      of "AD-like" phosphoepitopes.
AB  - 1. The individual and sequential influence of protein kinase C (PKC), protein
      kinase A (PKA) and mitogen-activated protein kinase (MAP kinase) on human brain
      tau was examined. 2. A range of PKC concentrations generated certain
      phosphoepitopes common with paired helical filaments. These epitopes were masked
      by higher PKC concentrations, suggesting the presence of multiple tau
      phosphorylation sites for which PKC exhibited differing affinities and/or
      conformational alterations in tau induced by sequential PKC-mediated
      phosphorylation. 3. Prior phosphorylation by PKC enhanced the nature and extent
      of AD-like tau antigenicity generated by subsequent incubation with MAP kinase
      yet inhibited that generated by subsequent incubation with PKA. 4.
      Dephosphorylation of tau prior to incubation with kinases significantly altered
      the influence of individual and multiple kinase incubation on tau antigenicity in
      a site-specific manner, indicating that prior in situ phosphorylation events
      markedly influenced subsequent cell-free phosphorylation. 5. In addition to
      considerations of the potential impact of tau phosphorylation by individual
      kinases, these findings extend previous studies which indicate that tau
      antigenicity, and, presumably, its behavior in situ, is influenced by the
      sequential and convergent influences of multiple kinases.

PMID- 10081607
TI  - Distinct responses of osphradial neurons to chemical stimuli and
      neurotransmitters in Lymnaea stagnalis L.
AB  - 1. In Lymnaea stagnalis L. (Pulmonata, Basommatophora) the neurons in the
      osphradium were visualized by staining through the inner right parietal nerve by
      5,6-carboxyfluorescein (5,6-CF). Three types of neurons were identified: three
      large ganglionic cells (GC1-3; 80-100 microns), the small putative sensory
      neurons (SC; 20 microns) and very small sensory cells (3-5 microns). 2. The
      ganglionic and putative sensory neurons were investigated by whole cell patch
      clamp method in current-clamp condition. The three giant ganglionic neurons (GC1
      3) located closely to the root of osphradial nerve, had a membrane potential (MP)
      between -30 and -70 mV and showed tonic or bursting activities. The small
      putative sensory cells (SCs) scattered throughout the osphradial ganglion,
      possessed a MP between -25 and -55 mV and showed an irregular firing pattern with
      membrane oscillations. At resting MP the GC1-3 cells were depolarized and
      increased the frequency of their firing, while the SCs were hyperpolarized and
      inhibited by NaCl (10(-2) M) and L-aspartate (10(-5) M) applied to the
      osphradium. 3. 5-Hydroxytryptamine (5HT, 10(-6) M), gamma-aminobutyric acid
      (GABA; 10(-6) M) and the GABAB agonist baclofen (10(-6) M) depolarized the
      neurons GC1-3 and increased their firing frequency. In contrast, on the GC1-3
      neurons, acetylcholine (Ach; 10(-6) M) and FMRFamide (10(-6) M) caused
      hyperpolarization and cessation of the firing activity. The 5HT effect was
      blocked by mianserin (10(-6) M) but picrotoxin (10(-5) M) failed to block the
      GABA-induced effect on the GC1-3 cells. 4. The small putative sensory neurons
      (SCs) were excited by Ach (10(-6) M) and 5HT (10(-6) M) but were inhibited by
      GABA (10(-6) M). FMRFamide (10(-6) M) had a biphasic response. The Ach effect was
      blocked by hexamethonium (10(-6) M) and tetraethylammonium (10(-6) M), indicating
      the involvement of nicotinic cholinergic receptors. 5. The distinct responses of
      the two populations of osphradial neurons to chemical stimuli and
      neurotransmitters suggest that they can differently perceive signals from
      environment and hemolymph.

PMID- 10081608
TI  - Hyperactivation of mitogen-activated protein kinase increases phospho-tau
      immunoreactivity within human neuroblastoma: additive and synergistic influence
      of alteration of additional kinase activities.
AB  - Mitogen-activated protein (MAP) kinase phosphorylates tau in cell-free analyses,
      but whether or not it does so within intact cells remains controversial. In the
      present study, microinjection of MAP kinase into SH-SY-5Y human neuroblastoma
      cells increased tau immunoreactivity toward the phosphodependent antibodies PHF-1
      and AT-8. In contrast, treatment with a specific inhibitor of MAP kinase
      (PD98059) did not diminish "basal" levels of these immunoreactivities in
      otherwise untreated cells. These findings indicate that hyperactivation of MAP
      kinase increases phospho-tau levels within cells, despite that MAP kinase
      apparently does not substantially influence intracellular tau phosphorylation
      under normal conditions. These findings underscore that results obtained
      following inhibition of kinase activities do not necessarily provide an
      indication of the consequences accompanying hyperactivation of that same kinase.
      Several studies conducted in cell-free systems indicate that exposure of tau to
      multiple kinases can have synergistic effects on the nature and extent of tau
      phosphorylation. We therefore examined whether or not such effects could be
      demonstrated within these cells. Site-specific phospho-tau immunoreactivity was
      increased in additive and synergistic manners by treatment of injected cells with
      TPA (which activates PKC), calcium ionophore (which activates calcium-dependent
      kinases), and wortmannin (which inhibits PIP3 kinase). Alteration in total tau
      levels was insufficient to account for the full extent of the increase in phospho
      tau immunoreactivity. These additional results indicate that multiple kinase
      activities modulate the influence of MAP kinase on tau within intact cells.

PMID- 10081609
TI  - The involvement of p53 in dopamine-induced apoptosis of cerebellar granule
      neurons and leukemic cells overexpressing p53.
AB  - 1. The pathogenesis of the selective degeneration of the dopaminergic neurons in
      Parkinson's disease is still enigmatic. Recently we have shown that dopamine can
      induce apoptosis in postmitotic neuronal cells, as well as in other cellular
      systems, thus suggesting a role for this endogenous neurotransmitter and
      associated oxidative stress in the neuronal death process. 2. Dopamine has been
      shown to be capable of inducing DNA damage through its oxidative metabolites. p53
      is a transcription factor that has a major role in determining cell fate in
      response to DNA damage. We therefore examined the possible correlation between
      dopamine-triggered apoptosis, DNA damage and levels of total phosphorylated p53
      protein in cultured mouse cerebellar granule neurons. 3. Marked DNA damage and
      apoptotic nuclear condensation and fragmentation were detected within several
      hours of exposure to dopamine. An associated marked threefold increase in p53
      phosphorylation was observed within this time window. Using a temperature
      sensitive p53 activation system in leukemia LTR6 cells, were found that p53
      inactivation dramatically attenuated dopamine toxicity. 4. We therefore conclude
      that DNA damage and p53 activation may have a role in mediating dopamine-induced
      apoptosis. Modulation of the p53 system may therefore have a protective role
      against the toxicity of this endogenous neurotransmitter and associated oxidative
      stress.

PMID- 10081610
TI  - Characterization of AT2 receptor expression in NIH 3T3 fibroblasts.
AB  - 1. A high expression of angiotensin II receptors and of angiotensin-converting
      enzyme (ACE) activity was detected in confluent NIH 3T3 fibroblasts. 2.
      Characterization with selective ligands, dithiothreitol, and GTP gamma S,
      indicated that only the AT2 subtype was expressed. 3. AT2 receptors and ACE
      expression were strictly dependent on the cell density and growth phase of the
      cells, with AT2 receptors being expressed earlier than ACE. In contrast, high
      expression of AT2 receptors irrespective of their growth state was observed in
      NIH 3T3 cells lacking contact inhibition upon neoplastic transformation with ras.
      4. Our results imply a possible relation of AT2 receptors to cell growth and cell
      cell contact.

PMID- 10081611
TI  - Tyrosines 905 and 915 of gp130 are required for maximum induction of m2
      muscarinic acetylcholine receptor and VIP gene transcription by cytokines in
      neuronal cells.
AB  - 1. Leukemia inhibitory factor action is mediated by a heterodimeric receptor
      consisting of two subunits, gp130 and the low-affinity leukemia inhibitory factor
      receptor (LIFR). 2. We used chimeric receptors containing the intracellular
      domain of either the LIFR or gp130 to identify regions of the receptors required
      for induction of the m2 muscarinic acetylcholine receptor gene in IMR-32 and SN56
      neuronal cells. 3. While chimeric receptors containing the intracellular domain
      of gp130 were able to induce transcription from both the m2 and the vasoactive
      intestinal peptide (VIP) gene promoters, chimeric receptors containing the
      intracellular domain of the LIFR were incapable of mediating induction of the m2
      gene despite being able to induce VIP transcription. 4. Deletion and mutagenesis
      studies identified two tyrosines, Y905 and Y915, which were required for maximal
      induction of the m2 and VIP genes. 5. Because Y905 and Y915 are reported to be
      the only tyrosine residues in gp130 that bind Stat1, these results suggest that
      this transcription factor plays a key role in the induction of transcription of
      both the m2 and the VIP genes.

PMID- 10081612
TI  - Localization of transforming growth factor beta in association with neuromuscular
      junctions in adult human muscle.
AB  - Transforming growth factors-beta 1, 2, and 3 are known for their regulatory
      function in embryogenesis, fibrogenesis, and tissue repair of different cell
      types. A trophic function of TGF-beta subclasses for motoneurons has been shown
      in vitro. TGF-beta 1 is a potent survival factor for cultured embryonic rat
      motoneurons. In addition, TGF-beta 1 stimulates proliferation of rat Schwann
      cells. Recently, TGF-beta 2 has been reported to be associated with the
      subsynaptic nuclei of mature rat neuromuscular junctions. In this study, we
      investigated the expression of TGF-beta 1, 2, and 3 at neuromuscular junctions in
      skeletal muscle of 11 adults without neuromuscular disease. On muscle biopsies,
      neuromuscular junctions were depicted by acetylcholine esterase reaction and
      acetylcholine receptor antibodies. TGF-beta 1; 2, and 3 were stained
      immunohistochemically with monoclonal antibodies. Some muscle fibers showed low
      levels of inhomogeneous immunoreactivity for both TGF-beta 1 and TGF-beta 3.
      Intense immunoreactivity of TGF-beta 1 and 3 was shown at the postsynaptic area
      of neuromuscular junctions. TGF-beta 2 was expressed in the same subcellular
      distribution, but less strongly. In conclusion, the colocalization of TGF-beta
      with neuromuscular junctions may suggest a significant function in neuromuscular
      communication.

PMID- 10081613
TI  - Partitioning lung and plasma proteins: circulating surfactant proteins as
      biomarkers of alveolocapillary permeability.
AB  - 1. The alveolocapillary membrane faces an extraordinary task in partitioning the
      plasma and lung hypophase proteins, with a surface area approximately 50-fold
      that of the body and only 0.1-0.2 micron thick. 2. Lung permeability is
      compromised under a variety of circumstances and the delineation between
      physiological and pathological changes in permeability is not always clear.
      Although the tight junctions of the epithelium, rather than the endothelium, are
      regarded as the major barrier to fluid and protein flux, it is becoming apparent
      that the permeability of both are dynamically regulated. 3. Whereas increased
      permeability and the flux of plasma proteins into the alveolar compartment has
      dire consequences, fortuitously the flux of surfactant proteins from the
      airspaces into the circulation may provide a sensitive means of non-invasively
      monitoring the lung, with important implications for treatment modalities. 4.
      Surfactant proteins are unique in that they are present in the alveolar hypophase
      in high concentrations. They diffuse down their vast concentration gradients
      (approximately 1:1500-7000) into the circulation in a manner that reflects lung
      function and injury score. Surfactant proteins vary markedly in size
      (approximately 20-650 kDa) and changes in the relative amounts appear
      particularly diagnostic with regard to disease severity. Alveolar levels of
      surfactant proteins remain remarkably constant despite respiratory disease and,
      unlike the flux of plasma proteins into the alveolus, which may reach equilibrium
      in acute lung injury, the flux of surfactant proteins is unidirectional because
      of the concentration gradient and because they are rapidly cleared from the
      circulation. 5. Ultimately, the diagnostic usefulness of surfactant proteins as
      markers of alveolocapillary permeability will demand a sound understanding of
      their kinetics through the vascular compartment.

PMID- 10081614
TI  - The cholinergic 'pitfall': acetylcholine, a universal cell molecule in biological
      systems, including humans.
AB  - 1. Acetylcholine (ACh) represents one of the most exemplary neurotransmitters. In
      addition to its presence in neuronal tissue, there is increasing experimental
      evidence that ACh is widely expressed in pro- and eukaryotic non-neuronal cells.
      Thus, ACh has been detected in bacteria, algae, protozoa, tubellariae and
      primitive plants, suggesting an extremely early appearance of ACh in the
      evolutionary process. 2. In humans, ACh and/or the synthesizing enzyme, choline
      acetyltransferase, has been demonstrated in epithelial cells (airways, alimentary
      tract, urogenital tract, epidermis), mesothelial (pleura, pericardium) and
      endothelial and muscle cells. In addition, immune cells express the non-neuronal
      cholinergic system (i.e. the synthesis of ACh can be detected in human leucocytes
      (granulocytes, lymphocytes and macrophages)), as well as in rat microglia in
      vitro. 3. The widespread expression of non-neuronal ACh is accompanied by the
      ubiquitous expression of cholinesterase activity, which prevents ACh from acting
      as a classical hormone. 4. Non-neuronal ACh mediates its cellular actions in an
      auto- and paracrine manner via the activation of the widely expressed nicotinic
      and muscarinic acetylcholine receptors, which can interfere with virtually all
      cellular signalling pathways (ion channels and key enzymes). 5. Non-neuronal ACh
      appears to be involved in the regulation of basic cell functions, such as
      mitosis, cell differentiation, organization of the cytoskeleton, cell-cell
      contact, secretion and absorption. Non-neuronal ACh also plays a role in the
      regulation of immune functions. All these qualities together may mediate the so
      called 'trophic property' of ACh. 6. Future experiments should be designed to
      analyse the cellular effects of ACh in greater detail. The involvement of the non
      neuronal cholinergic system in the pathogenesis of chronic inflammatory diseases
      should be investigated to open up new therapeutic strategies.

PMID- 10081615
TI  - Renin-angiotensin system stimulates cardiac and renal disorders in Tsukuba
      hypertensive mice.
AB  - 1. The role of the renin-angiotensin system (RAS) in cardiac hypertrophy and
      nephropathy was examined in Tsukuba hypertensive mice (THM) carrying both human
      renin and angiotensinogen genes. 2. Tsukuba hypertensive mice were treated with
      20 mg/kg per day lisinopril, 30 mg/kg per day hydralazine or nothing.
      Administration of drugs was performed for 6 months from 12 weeks of age; water
      intake and urine volume were measured and urine albumin excretion, heart to
      bodyweight ratio and the glomerulosclerosis index were examined. 3. Systolic
      blood pressure was significantly lowered by treatment with lisinopril and
      hydralazine. Urine volume, water intake and urinary albumin excretion were
      significantly decreased by lisinopril. When hydralazine was administered to THM,
      these parameters were transiently decreased, but eventually reached almost the
      same levels as those in the untreated group. The heart to bodyweight ratio was
      significantly decreased by lisinopril, but not by hydralazine. The
      glomerulosclerosis index was significantly lowered by lisinopril, but the index
      in the hydralazine group was not significantly different from that in the
      untreated group. 4. These results suggest that the RAS plays an important role in
      the progression of cardiac hypertrophy in THM. In addition, the RAS may also play
      an important role in the progression of nephropathy; however, this may also be
      partially regulated by elevated blood pressure in the short term.

PMID- 10081616
TI  - Effects of BDF 9148 on the action potentials and contractions of left ventricles
      from normo- and hypertensive rats.
AB  - 1. The aim of the present study was to test the hypothesis that responses to BDF
      9148, which prolongs the opening of sodium channels, are reduced in the
      spontaneously hypertensive rat (SHR) left ventricle in the presence of
      hypertrophy and failure. 2. We studied the effects of BDF 9148 on the action
      potentials and contractions of left ventricles from 5-week-old prehypertensive,
      14-week-old hypertensive, 6- and 12-month-old hypertension-associated hypertrophy
      and 18-month-old hypertension-induced heart failure SHR and age-matched Wistar
      Kyoto normotensive (WKY) rats. 3. Action potentials and left ventricular
      contractions did not alter in the early stages of hypertension (14-week-old SHR).
      The diastolic membrane potential did not change with hypertension-associated
      hypertrophy, but there was a reduction in amplitude and a prolongation of action
      potentials in the left ventricles of 6-18-month-old SHR. Cardiac stimulation
      responses and maximum contractions to 10(-6) mol/L isoprenaline were reduced at 6
      months, whereas the maximum contractions to 10(-2) mol/L CaCl2 were only reduced
      in left ventricles of 18-month-old SHR. 4. At concentrations ranging from 10(-7)
      to 3 x 10(-6) mol/L, BDF 9148 increased the amplitude and prolonged the duration
      of action potentials and augmented the force in WKY rat left ventricles. The
      augmenting effects of BDF 9148 at 3 x 10(-6) mol/L were smaller than at 10(-6)
      mol/L, possibly because the high concentration of BDF 9148 was also blocking
      calcium channels. Similar effects were observed with BDF 9148 in the early stages
      of hypertension (14-week-old SHR). 5. In the presence of persistent hypertension
      associated hypertrophy of the SHR left ventricle at > or = 6 months, the effects
      of BDF 9148 on action potentials and contractions were significantly reduced to a
      small extent. This impairment of the response to BDF 9148 may reflect the reduced
      contractility of the SHR left ventricle and/or it may indicate that the response
      to the opening of sodium channels is altered from 6 months of age. 6. In summary,
      most of the response of BDF 9148 is maintained in the presence of hypertrophy and
      failure. Thus, BDF 9148 may have some potential for the treatment of heart
      failure.

PMID- 10081617
TI  - Effect of propranolol on central neurotransmitter release in Wistar rats analysed
      by brain microdialysis.
AB  - 1. The effect of propranolol on amino acid neurotransmitter release in the
      rostral ventrolateral medulla (RVLM) was examined in urethane-anaesthetized male
      Wistar rats. 2. Amino acids released in the RVLM in response to intravenous
      administration of propranolol (0.4 mg/kg per min; n = 6) or nitroglycerin (0.02
      mg/kg per min; n = 5) were determined by the brain microdialysis method. 3. Amino
      acids in dialysates were analysed by high-performance liquid chromatography and
      were quantified by ultraviolet absorbance. 4. Administration of both intravenous
      propranolol and nitroglycerin significantly decreased arterial blood pressure.
      Heart rate was decreased only by propranolol. 5. The reduction in arterial blood
      pressure produced by intravenous propranolol was accompanied by a decrease in the
      release of the excitatory amino acid glutamate in the RVLM. 6. The reduction in
      arterial blood pressure following intravenous nitroglycerin was not accompanied
      by a release of glutamate. 7. There were no significant changes in the levels of
      other amino acids (glycine, taurine, GABA) following either propranolol or
      nitroglycerin. 8. The decrease in glutamate release in the RVLM may account, in
      part, for the central depressor mechanism of propranolol.

PMID- 10081618
TI  - Different responses to surgical stress between extra domain A+ and plasma
      fibronectins.
AB  - 1. Fibronectins (FN) are believed to have a role in haemorheological perturbation
      associated with tissue damage. Fibronectins exist in two antigenically related
      forms, plasma (p) and cellular fibronectin, which has the extra domain sequences
      A (EDA) or B (EDB). The present study was designed to determine changes in plasma
      p-FN and EDA + FN under different types of surgical stress. 2. Sixty-two patients
      were divided into three groups: (i) group A, 33 patients undergoing hepato
      pancreato-biliary surgery; (ii) group B, 19 patients undergoing laparoscopic
      cholecystectomy; and (iii) group C, 10 patients with postoperative complications.
      Plasma FN and EDA + FN levels were measured in these patients undergoing
      different types of surgical operation and either with or without liver cirrhosis
      using an enzyme-linked immunosorbent assay. 3. After surgery, a significant
      decrease in p-FN levels and a significant increase in EDA + FN levels was
      observed in all patient group compared with pre-operative levels. The duration of
      increased EDA + FN levels, but not p-FN levels, in group A patients was
      significantly longer than in group B patients. Although changes in p-FN levels
      between patients with and without liver cirrhosis were significantly different,
      there were no significant differences in the EDA + FN levels between these two
      patient groups. 4. In conclusions, EDA + FN and p-FN levels were found to exhibit
      opposite responses to surgical stress. Furthermore, with greater surgical stress,
      greater increases in EDA + FN levels were seen. The presence of liver cirrhosis
      had no significant effect on EDA + FN levels during the perioperative period;
      however, p-FN levels were significantly affected. 5. Thus, it is suggested that
      plasma EDA + FN levels reflect the magnitude of surgical stress more closely than
      do p-FN levels.

PMID- 10081619
TI  - Reduction of human recombinant type II phospholipase A2 and prostaglandin F2
      alpha release by microtubule depolymerizing agents.
AB  - 1. The present study examines the effects of the microtubule depolarizing agent
      colchicine on secretory type II phospholipase A2 (PLA2) function in Chinese
      hamster ovary (CHO) cells that specifically overexpress human type II PLA2 and
      the effect of both colchicine and tubulazole on the release of type II PLA2 and
      prostaglandin (PG) F2 alpha from human placental explants. 2. Significant
      suppression by colchicine (0.01-10 mumol/L) of PLA2 activity (P < 0.00001),
      immunoreactive type II PLA2 (irPLA2; P < 0.00001) and PGF 2 alpha release (P <
      0.01) was observed in medium from overexpressing CHO cells. These effects were
      significantly reduced (P < 0.0001) in the presence of 10 mumol/L taxol, an agent
      that prevents depolymerization of microtubules. The addition of 30 mumol/L
      arachidonic acid significantly reduced (P < 0.0001) the inhibition of PGF2 alpha
      production in CHO cell lines. 3. The addition of 1 mumol/L colchicine to human
      placental explants for 24 h significantly reduced irPLA2 (P < 0.00001) and PGF2
      alpha production (P < 0.00001). Similarly, 1 mumol/L tubulazole significantly
      blocked irPLA2 (P < 0.001) and PGF2 alpha (P < 0.0001). 4. At 10 mumol/L, taxol
      significantly reduced irPLA2 inhibition by colchicine (n = 8; P < 0.05) and
      tubulazole (n = 8; P < 0.05). Similarly, taxol significantly reduced the
      reduction in PGF2 alpha production caused by colchicine (P < 0.001) and by
      tubulazole (P < 0.001). 5. These results suggest that integrity of the
      microtubule system is required for PLA2 function and the subsequent production of
      pro-inflammatory mediators.

PMID- 10081620
TI  - Effects of cicletanine on the progression of renal failure in 5/6 nephrectomized
      hypertensive rats.
AB  - 1. The effect of cicletanine, a novel antihypertensive agent with natriuretic
      activity, on blood pressure and progression of renal failure of 5/6
      nephrectomized spontaneously hypertensive rats with salt loading was examined. 2.
      All nephrectomized rats were randomly assigned to one of four groups and their
      diet was changed from a normal- to a high-salt (5.5% NaCl) diet for the next 10
      weeks. Either 10 or 50 mg/kg per day cicletanine (low- and high-dose cicletanine,
      respectively) or 10 mg/kg per day trichlormethiazide were administered to rats
      during this period once a day. During the experimental period, urine volume,
      urinary excretion of sodium, protein, prostaglandin (PG) E2 and 6-keto-PGF1 alpha
      and systolic blood pressure (SBP) were measured every 2 weeks. 3. Systolic blood
      pressure was significantly reduced by the administration of trichlormethiazide
      and the higher dose of cicletanine, but not by the lower dose of cicletanine. 4.
      In contrast with changes to SBP, levels of serum creatinine in rats treated with
      both doses of cicletanine were significantly lower than in controls (0.57 +/-
      0.12, 0.78 +/- 0.12 and 1.68 +/- 0.26 mg/dL for high- and low-dose cicletanine
      and control, respectively). 5. Urinary excretion of both PGE2 and 6-keto-PGF1
      alpha were significantly increased in groups treated with high and low doses of
      cicletanine compared with control. In rats treated with trichlormethiazide, PGE2
      and 6-keto-PGF1 alpha levels were significantly decreased compared with control.
      6. In contrast with changes in SBP, marked glomerular sclerosis with hyalinosis
      found in the control group was not ameliorated by trichlormethiazide treatment.
      These changes were not observed in rats treated with low- and high-dose
      cicletanine, particularly those treated with the higher dose of cicletanine. 7.
      These data suggest that administration of cicletanine has a beneficial protective
      effect regarding the progression of renal failure, regardless of the level of
      blood pressure, through a direct and/or indirect action on the glomerulus.

PMID- 10081621
TI  - Erythromycin derivatives ABT 229 and GM 611 act on motilin receptors in the
      rabbit duodenum.
AB  - 1. The present study was undertaken to determine whether the macrolide antibiotic
      erythromycin, its stable motilide derivatives ABT 229 and GM 611 and motilin act
      at the same receptors on intestinal muscle 2. Each compound contracted the
      longitudinal muscle of the rabbit duodenum in a concentration-dependent manner
      that was unaffected by 1 mumol/L tetrodotoxin. The potency order (pEC50 values in
      brackets) was motilin (8.4), ABT 229 (7.6), GM 611 (7.5) and erythromycin (6.0).
      3. The motilin receptor antagonists GM 109 and [phe3, leu13]-motilin, both
      shifted the concentration-response curves for each agonist to the right, but did
      not affect concentration-response relationships for the muscarinic agonist
      carbachol. Schild regression analysis yielded similar pA2 values for GM 109 (in
      the range 7.2-7.5) for all agonists. This analysis was not done for [phe3,
      leu13]motilin, which was a non-competitive antagonist and partial agonist. 4. It
      is concluded that erythromycin, the motilides and motilin act at the same
      (motilin) receptor on rabbit duodenal muscle and do not have any detectable
      actions at other receptors in this preparation.

PMID- 10081622
TI  - Relationships between the endothelin and nitric oxide pathways.
AB  - 1. In the normal blood vessel, the vascular endothelium regulates the tone of the
      underlying smooth muscle and the reactivity of blood elements, such as platelets
      and neutrophils, by the release of mediators, in particular nitric oxide (NO) and
      endothelin-1 (ET-1). 2. Nitric oxide is a potent vasodilator that also inhibits
      platelet and neutrophil aggregation and adhesion; ET-1 is the most potent
      mammalian vasoconstrictor peptide yet found. Recently, much research effort has
      focused on examining the interactions between these two important mediators. At a
      simple level, ET-1 acts on specific receptors on the endothelium to increase the
      release of NO, while NO depresses the production and/or release of ET-1 from
      endothelial cells. 3. While ET-1 appears to have a relatively small influence on
      the basal regulation of blood pressure, NO appears central. For example,
      inhibition of NO production in normotensive animals produces a marked elevation
      in blood pressure. 4. Conversely, numerous vascular disease states have been
      associated with elevations in the production and/or release of ET-1 and it has
      been implicated in the deleterious changes associated with ischaemia-reperfusion
      injury, subarachnoid haemorrhage and hypertension. In these conditions, NO
      production may also be increased by the induction of NO synthetic pathways within
      the vascular smooth muscle. Endothelin-1 may also be produced by the vascular
      smooth muscle under similar circumstances. 5. Therefore, in pathological states,
      a new balance between NO and ET-1 production may be central to changes in blood
      vessel reactivity, smooth muscle proliferation and blood coagulability.

PMID- 10081623
TI  - Acute interactions between endothelin and nitric oxide in the control of renal
      haemodynamics.
AB  - 1. Endogenous endothelin (ET) does contribute to control of renal vascular tone
      via nitric oxide (NO)-dependent vasodilation in the rat. 2. Endothelin mediates
      some of the renal vascular responses to acute nitric oxide synthase (NOS)
      inhibition, being particularly important when a rise in renal perfusion pressure
      occurs. 3. Tonically produced NO blunts the renal vasoconstrictor responses to
      acutely administered ET. 4. The similarity between the renal vascular responses
      to ET administration and NOS inhibition is not fortuitous but, in part, reflects
      important interactions between these vasoactive agents.

PMID- 10081624
TI  - Chronic studies on the interaction between nitric oxide and endothelin in
      cardiovascular and renal function.
AB  - 1. Chronic inhibition of nitric oxide synthase (NOS) results in a persistent
      hypertension, while chronic blockade of endothelin ETA receptors has little
      effect on arterial pressure. These findings indicate that nitric oxide (NO) plays
      a more significant role than ET-1 in the long-term maintenance of arterial
      pressure. 2. Although endothelin (ET) appears to contribute to the hypertension
      in the early stages of NOS inhibition, blockade of either ETA or both ETA and ETB
      receptors has only a minor effect on the hypertension beyond the initial 2 weeks
      of NOS inhibition. 3. Endothelin may play a role in vascular lesion development
      associated with NOS inhibition, at least within the kidney, which may be related
      to angiotensin II activity. 4. The processes involved in the hypertension
      associated with chronic NOS inhibition appear to be dynamic and may include an
      evolution of ET-1 action. Variability in results from different laboratories may
      be related to genetic factors and choice of pharmacological agents.

PMID- 10081625
TI  - Nitric oxide, endothelin and nephron transport: potential interactions.
AB  - 1. Nitric oxide (NO) is produced and/or regulates transport in many segments of
      the nephron, including the proximal convoluted tubule, proximal straight tubule,
      thick ascending limb, cortical collecting duct and inner medullary collecting
      duct. 2. Endothelin (ET) is produced and/or regulates nephron transport in many
      of the segments that produce NO or in which transport is regulated by NO. 3. Four
      potential interactions between NO and ET are: (i) NO and ET may be antagonistic;
      (ii) NO and ET may be complementary; (iii) the effects of ET may be mediated via
      NO; and (iv) the effects of NO may be mediated by ET. 4. In conclusion, direct
      studies examining the interactions between NO and ET are few. However,
      circumstantial evidence suggests there may be many interactions between NO and ET
      in the regulation of nephron transport. In particular, recent data obtained from
      the collecting duct and thick ascending limb indicate that the effects of ET may
      be mediated by the production of NO and stimulation of its second messenger
      cascade.

PMID- 10081626
TI  - Co-operation between endothelin and nitric oxide in promoting endothelial cell
      migration and angiogenesis.
AB  - 1. Among the diverse functions of endothelins (ET), their role in the remodelling
      of blood vessels remains poorly examined. In the present review, we summarize
      findings obtained in our laboratory and present four independent lines of
      evidence to support this novel function. We also demonstrate that the motogenic
      and angiogenic effects of ET are mediated via the ETB receptor and that the
      functional endothelial nitric oxide synthase (NOS) is requisite for this action.
      2. We demonstrated that ET stimulates transmigration of endothelial cells in a
      modified Boyden chamber and accelerates endothelial wound healing acting via ETB
      receptors. 3. In genetically engineered Chinese hamster ovary cells expressing
      either ETB receptor or endothelial NOS or both, application of ET results in
      accelerated cell migration only when the receptor and the enzyme are coexpressed.
      Application of antisense oligonucleotides producing a specific knockdown of the
      endothelial NOS results in the loss of ET ability to stimulate endothelial cell
      migration in response to ET. 4. Finally, using a novel model of in vivo
      angiogenesis, we were able to demonstrate that ET enhances formation of new
      vessels, but this effect requires functional endothelial NOS. 5. The described
      phenomenon of NO production, serving as a prerequisite for endothelial cell
      locomotion in response to activation of ETB receptor may explain a host of
      pathophysiological observations on inadequate angiogenesis despite enhanced
      generation of ET-1. 6. Based on the contribution of endothelial cell migration to
      angiogenesis, these data may implicate insufficient NO production in pathological
      states (e.g. atherosclerosis, heart failure and hypertension) in the
      inappropriate response to angiogenic stimuli.

PMID- 10081627
TI  - Deciding what the competent prescriber should know.

PMID- 10081628
TI  - Review of immunosuppressive usage in pancreas transplantation.
AB  - Throughout 1997, nearly 10,000 pancreas transplants have been performed
      worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1
      yr patient survival rate exceeds 90% and pancreas graft survival (complete
      insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas
      after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA).
      According to registry data, rejection accounts for 32% of graft failures in the
      first year after pancreas transplantation. However, improvements are expected to
      continue with the evolution of treatment protocols. Most pancreas transplant
      centers employ quadruple drug immunosuppression with anti-lymphocyte induction
      with either a monoclonal or polyclonal antibody agent. In recent years, there has
      been an overall decline in the use of antibody induction therapy from 90% during
      the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997.
      Maintenance immunosuppression is triple therapy consisting of a calcineurin
      inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite
      (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were
      managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used
      in approximately 20% of cases and a new microemulsion formulation of cyclosporine
      (Neoral) has replaced Sandimmune in contemporary post-transplant
      immunosuppression. In addition, MMF is replacing AZA as part of the standard
      immunosuppressive regimen after pancreas transplantation. At present, a number of
      centers are conducting various trials with new drug combinations including either
      Neoral or tacrolimus in combination with steroids and MMF with or without
      antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic
      graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The
      current array of new immunosuppressive agents are providing more effective
      control of rejection and permitting solitary pancreas transplantation to become
      an accepted treatment option in diabetic patients without advanced complications.
      The apparent potency of new drug combinations has also resulted in a resurgence
      of interest in steroid withdrawal. Immunosuppressive strategies will continue to
      evolve in order to achieve effective control of rejection while minimizing injury
      to the allograft and risk to the patient. In addition, new regimens must not only
      address the issue of specific drug toxicities but also long-term economic,
      metabolic, and quality of life outcomes. Pancreas transplantation will remain an
      important alternative in the treatment of diabetic patients until other
      strategies are developed that can provide equal glycemic control with less
      immunosuppression and overall morbidity.

PMID- 10081629
TI  - Helicobacter pylori antibodies in hemodialysis patients and renal transplant
      recipients.
AB  - In this cross-sectional, controlled study, Helicobacter pylori (H. pylori)
      infection, a probable factor in the development of gastrointestinal problems, was
      investigated in dialysis patients and renal transplant recipients. Forty-seven
      dialysis patients (22 male, 25 female, mean age of 36.6 +/- 15 yr (range 18-83
      yr)), 57 renal transplant recipients (39 male, 18 female, mean age of 36.8 +/- 10
      yr (range 19-60 yr)) and 55 healthy individuals (34 male, 21 female, mean age of
      33.4 +/- 9.6 yr (range 21-58 yr)) were included and no significant difference was
      found in the study groups. The mean time spent on dialysis in the hemodialysis
      group was 32.5 +/- 27.7 months (range 1-100 months). H. pylori antibodies were
      detected in 22 of 57 (38.6%) patients in the transplantation group, 31 of 47
      (65.9%) patients in the dialysis group and 39 of 55 (72.5%) in the control group.
      No correlation was found between H. pylori infection and age, sex, primary
      disease, frequency of dialysis, duration and type of transplantation and the
      immunosuppressive therapy. However, patients with H. pylori antibodies spent a
      shorter time on dialysis compared to patients without the antibodies (26.6 +/-
      23.5 vs 44.1 +/- 32.1 months, p = 0.038). The frequency of H. pylori infection in
      the transplantation group was significantly lower than the control and dialysis
      groups (p < 0.01). This finding may be explained on the basis of decreased
      humoral antibody response to H. pylori infection, secondary to immunosuppressive
      therapy rather than decreased incidence of infection in the transplantation
      group. Finally, we concluded that the value of the serological test for diagnosis
      of H. pylori infection should be interpreted cautiously in these patient groups.

PMID- 10081630
TI  - Human parvovirus B19 infection in organ transplant recipients.
AB  - We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV
      B19) infection presenting as a severe pancytopenia 1 month after transplantation.
      Bone marrow aspiration revealed severe erythroid hypoplasia with giant and
      dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA
      detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after
      administration of intravenous immunoglobulins. Nineteen cases of HPV B19
      infection in organ transplant recipients have been so far reported in the
      literature. Immunocompromised patients should be considered at risk from
      developing symptomatic HPV B19 infections. In such patients, specific anti-HPV
      B19 IgM and IgG antibodies may be absent or transient and therefore their
      negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow
      smear morphological findings may suggest the diagnosis but testing for viral DNA
      by PCR is mandatory. Patients may spontaneously recover. However, since specific
      anti-viral therapy is not currently available, intravenous immunoglobulin
      administration appears to be the more efficacious treatment.

PMID- 10081631
TI  - Correlation between von Willebrand factor levels and early graft function in
      clinical liver transplantation.
AB  - Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC)
      activation and damage in nearly every liver transplantation; the extent of these
      changes influences early graft function. Upon reperfusion, activated SEC show
      increased expression of adhesion molecules, including von Willebrand factor (vWF)
      which is released into the circulation. This study was designed to evaluate the
      levels of vWF measured in the caval effluent and correlate these findings with
      known markers of SEC damage and early graft function. Data were obtained from 35
      patients undergoing orthotopic liver transplantation (LTx). Two samples were
      taken from each patient for measurement of vWF: a) from the portal vein
      immediately prior to reperfusion; and b) from the first 50 ml of the caval
      effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid
      (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were
      divided into two groups based on early graft function. Poor early graft function
      (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase
      (ALT) level > 2500 U/L during the first three postoperative days (POD) and a
      prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good
      early graft function (GEGF). In patients with GEGF, vWF levels dropped
      significantly between the two time points. This change was not observed in those
      with PEGF. A positive linear correlation was observed in the PEGF group between
      vWF and HA and IL-6. The different pattern of change in vWF between the two
      groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF,
      suggest that vWF may be a useful marker of early graft function.

PMID- 10081632
TI  - Screening for basiliximab exposure-response relationships in renal
      allotransplantation.
AB  - The immunosuppressant basiliximab--a chimeric monoclonal antibody specific to the
      interleukin-2 receptor on activated T-lymphocytes--significantly reduces the
      incidence of acute cellular rejection following renal transplantation. Screening
      for exposure-response relationships was performed within a randomized, blinded,
      placebo-controlled efficacy trial in which patients received 40 mg basiliximab
      (20 mg on days 0 and 4) by intravenous infusion in addition to cyclosporine and
      corticosteroids. In a subset of patients, serum samples were collected pre
      transplant and once in weeks 2, 3 and 4 for determination of basiliximab
      concentrations. A population pharmacostatistical model was used to derive
      individual empirical Bayes estimates of each patient's pharmacokinetic
      parameters. Biopsy-confirmed acute rejection episodes were recorded to month 6
      post-transplant. Forty basiliximab-treated patients were evaluated, 30 men and 10
      women, aged 48 +/- 12 yr (range, 24-73) and weighing 72.4 +/- 12.9 kg (range,
      52.5-107.5). The basiliximab distribution volume was 7.5 +/- 1.7 L, the half-life
      7.5 +/- 2.5 d and the clearance 33 +/- 12 mL/h. There was no clinically relevant
      influence of weight, age, or gender on basiliximab disposition. Receptor
      saturating serum basiliximab concentrations (> 0.2 microgram/mL) were maintained
      for 41 +/- 23 d. Twenty-five patients remained rejection-free over the 6-month
      observation period, while a total of 26 biopsy-confirmed acute rejection episodes
      occurred in the remaining 14 patients. Of these episodes, 12 occurred during
      receptor blockade. No apparent relationship to basiliximab concentration on the
      day of onset was observed range, 0.1-9.0 microgram/mL) nor did the time of
      suppression offset represent a period of increased risk for rejection episodes.
      Fourteen rejection episodes occurred after basiliximab had cleared from the
      serum. The durations of receptor suppression preceding these events did not
      differ compared with those in patients who remained rejection-free: 32 +/- 11
      versus 45 +/- 26 d, respectively (p = 0.1269). Given the durations of receptor
      saturation achieved with the chosen basiliximab regimen, this screen for exposure
      response relationships did not identify the duration of receptor saturation in
      peripheral blood as a predictive factor for acute rejection episodes. Further
      exploration for exposure-effect relationships in a larger population is
      warranted.

PMID- 10081633
TI  - Cytokine mRNA profiles in Epstein-Barr virus-associated post-transplant
      lymphoproliferative disorders.
AB  - Cytokine mRNA patterns were analyzed in 11 post-transplant lymphoproliferative
      disorder (PTLD) specimens using qualitative reverse-transcriptase polymerase
      chain reaction (RT-PCR). In each case, a pattern of IL2-, IFN gamma-, IL4+, IL10+
      was seen. A similar pattern was observed in a spleen sample from 1 patient with
      contemporaneous PTLD elsewhere. Semiquantitative RT-PCR for cytokine message was
      performed using RNA from bronchoalveolar lavage (BAL) specimens obtained from 2
      patients with pulmonary PTLD. In both cases, IL4 message predominated. Reduction
      of message coincided with resolution of the tumors. The pattern differed from
      that seen in 1 patient with acute pulmonary rejection, in which RT-PCR of BAL
      cells showed predominance of IL6 and IFN gamma. We conclude that at least some
      PTLDs exist within a T-helper cell type 2 (Th2)-like cytokine microenvironment.
      The presence of a similar mRNA pattern in an extratumoral specimen at the time of
      PTLD suggests that it may reflect a systemic phenomenon. Disappearance of this
      pattern following PTLD resolution indicates its dynamic nature and is consistent
      with the hypothesis that specific cytokines contribute to the development of
      PTLDs.

PMID- 10081634
TI  - Correlates of support for organ donation among three ethnic groups.
AB  - Telephone interviews about organ donation were conducted with 4880 white
      respondents, 634 African-American respondents and 566 Hispanic respondents. Forty
      three percent (42.9%) of whites, 31.2% of Hispanics and 22.6% of African
      Americans reported that they were willing to donate their organs after their
      death (p < 0.001). Logistic regression analysis revealed three significant
      correlates of willingness to donate across all ethnic groups: having had a family
      discussion about end-of-life issues; the belief that a doctor does all he or she
      can to save a life before pursuing donation; and concerns about surgical
      'disfigurement' of a relative's body after donation. Concerns in relation to body
      disfigurement were more prevalent among African-American and Hispanic respondents
      (p < 0.001) than among white respondents. Public education should: a) stress the
      need for family communication about end-of-life issues including organ donation;
      b) underline the fact that donation is considered only after all efforts to save
      the life of the patient are exhausted; and c) reassure minorities that the body
      of the donor is treated respectfully and not disfigured.

PMID- 10081635
TI  - Cost-utility analysis of living-donor kidney transplantation followed by pancreas
      transplantation versus simultaneous pancreas-kidney transplantation.
AB  - For a type I diabetic with end-stage renal disease, the choice between a kidney
      alone transplant from a living-donor (KA-LD) and a simultaneous pancreas kidney
      (SPK) transplant remains a difficult one. The prevailing practice seems to favor
      KA-LD over SPK, presumably due to the superior long-term renal graft survival in
      KA-LD and the elimination of the lengthy waiting time on the cadaver transplant
      list. In this study, two treatment options, KA-LD followed by pancreas-after
      kidney (PAK) and SPK transplant, are compared using a cost-utility decision
      analysis model. The decision tree consisted of a choice between KA-LD + PAK and
      SPK. The analysis was based on a 5-yr model and the measures of outcome used in
      the model were cost, utility and cost-utility. The expected 5-yr cost was
      $277,638 for KA-LD + PAK and $288,466 for SPK. When adjusted for utilities, KA-LD
      + PAK at a cost of $153,911 was less cost-effective than SPK at a cost of
      $110,828 per quality-adjusted year. One-way sensitivity analyses were performed
      by varying patient and graft survival probabilities, utilities and cost. SPK
      remained the optimal strategy over KA-LD + PAK across all variations. Two-way
      sensitivity analysis showed that in order for KA-LD + PAK to be at least as cost
      effective as SPK, 5-yr pancreas and patient survival rates following PAK would
      need to surpass 86 and 80%. In conclusion, according to the 5-yr cost-utility
      model presented in this study, KA-LD followed by PAK is less cost-effective than
      SPK as a treatment strategy for a type I diabetic with end-stage renal disease.
      For patients interested in the benefits of a pancreas transplant, it would be
      reasonable to offer SPK as the optimal treatment, even if a living kidney donor
      is available.

PMID- 10081636
TI  - Is the presence of surgically treatable coronary artery disease a
      contraindication to liver transplantation?
AB  - Advanced coronary artery disease has been traditionally considered an absolute
      contraindication to orthotopic liver transplantation where chronic liver failure
      significantly increases the surgical risk for coronary artery bypass grafting.
      Performing a simultaneous coronary artery bypass grafting and liver transplant is
      a theoretically attractive strategy in liver transplant candidates with coronary
      artery disease in need of revascularization. In the present article, we report a
      successful simultaneous coronary artery bypass grafting and orthotopic liver
      transplant with 1-yr post-operative follow-up and we discuss the rationale for
      this approach. In selected cases, the presence of advanced coronary artery
      disease should not be considered an absolute contraindication to liver
      transplantation.

PMID- 10081637
TI  - Addisonian crisis in a liver transplant patient due to fluconazole withdrawal.
AB  - Fluconazole is an antifungal agent commonly used in liver transplant patients. In
      addition to its antifungal activity, it is a potent inhibitor of the liver
      cytochrome P450 enzymes. These enzymes degrade a wide range of metabolically
      active compounds including glucocorticoids. In this report, we identify an
      episode of Addisonian crisis that occurred in a liver transplant patient
      receiving prednisone immunosuppression after fluconazole was discontinued. We
      postulate the mechanism for the crisis was a reversal of the fluconazole-induced
      suppression of the P450 enzymes. The resulting increased activity altered the
      patient's glucocorticoid metabolism leading to an Addisonian crisis.

PMID- 10081638
TI  - Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis
      carinii infection in a liver transplant patient receiving tacrolimus.
AB  - We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP)
      associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation
      and tacrolimus based immunosuppression. Radiologically, bilateral diffuse
      interstitial shadowing and patchy alveolar infiltrates developed after switching
      the patient from cyclosporin A to tacrolimus for persistent rejection.
      Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic
      organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in
      the case of negative BAL the possibility of an atypical P. carinii infection has
      to be considered for differential diagnosis of pneumonia in immunocompromised
      patients after organ transplantation. The combination of BOOP with PCP after
      liver transplantation and tacrolimus medication has not been reported previously.

PMID- 10081639
TI  - Successful cytokine treatment of aplastic anemia following living-related
      orthotopic liver transplantation for non-A, non-B, non-C hepatitis.
AB  - The relationship between aplastic anemia and viral hepatitis is well recognized,
      and such patients usually have a high mortality. We successfully treated a case
      of aplastic anemia following living-related orthotopic liver transplantation
      (LROLT) for non-A, non-B, non-C hepatitis. A 2-yr-old boy with fulminant hepatic
      failure from non-A, non-B, non-C hepatitis received LROLT. Before
      transplantation, he had pancytopenia which was probably hepatitis associated, and
      viral suppression was suspected after bone marrow (BM) biopsy. After the
      transplantation, he developed progressive pancytopenia and a diagnosis of
      aplastic anemia was made via BM biopsy. With immunosuppressant agents
      (cyclosporine, methylprednisolone), cytokine therapy (granulocyte-colony
      stimulating factor (G-CSF), macrophage-colony stimulating factor (M-CSF),
      recombinant human erythropoietin (rhEPO)) was effectual and the patient recovered
      from pancytopenia. He was discharged from the hospital 57 d after the liver
      transplantation and remains well 1 yr after LROLT. Combined cytokine therapy with
      high doses of G-CSF, M-CSF and rhEPO appeared to be effective in the treatment of
      aplastic anemia following liver transplantation for non-A, non-B, non-C
      hepatitis. Since M-CSF activates macrophages, it may have contributed to the
      graft rejection. Careful consideration should be given to the use of high-dose M
      CSF in liver transplant patients.

PMID- 10081640
TI  - Organ transplantation after fatal cyanide poisoning.

PMID- 10081641
TI  - Role of P-selectin expression in hepatic ischemia and reperfusion injury.
AB  - BACKGROUND: Researchers have shown that reperfusion of ischemic tissues initiates
      a complex series of reactions that paradoxically injure tissues. Although several
      mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion
      (I/R) injury, much attention has focused on adhesion molecules. Our research is
      intended to show the kinetics of P-selectin in the liver in response to I/R
      injury. METHODS: Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6
      mice and 20 P-selectin-deficient (K-O) mice. P-selectin expression was measured
      in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well as in
      control and sham animals. The animals were injected with radio-labeled P-selectin
      monoclonal antibody and the organs were harvested for counts/g tissue, expressed
      as the percentage injected dose. Serum liver enzymes were measured and
      pathological sections of ischemic and control livers were performed. The unpaired
      t-test was used for statistical analysis. RESULTS: P-selectin expression showed
      two peaks in this animal model. The first peak was at 20 min and the second peak
      at 5 h of reperfusion (p < 0.001). We documented an 8-fold increase in aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) levels 10 h following I/R injury. Pathological specimens showed periportal
      necrosis consistent with an ischemic event. P-selectin K-O mice showed no up
      regulation as a separate control group, and the liver enzymes were significantly
      lower than the wild-type mice at 10 h (p < 0.001). CONCLUSION: P-selectin has a
      bimodal expression following hepatic I/R injury. The first peak is attributed to
      the Weibel-Palade bodies and the second to new translational P-selectin. We noted
      no difference in the up-regulation of P-selectin in the ischemic and non-ischemic
      liver lobes in the same animal.

PMID- 10081642
TI  - The use of positive B cell flow cytometry crossmatch in predicting rejection
      among renal transplant recipients.
AB  - We performed retrospective flow cytometry crossmatch (FCXM) on 106 renal graft
      recipients who were transplanted based on current T cell negative serologic
      crossmatch. T and B cell FCXMs were performed on current and historical peak
      reactive post-transplant sera using 1024-channel flow cytometer and the shift in
      median channel fluorescence (SMCF) over the negative control was calculated. Cut
      off values for a positive T and B crossmatch, > 40 and > 80 SMCF, respectively,
      were determined based on previous retrospective analysis of the data in the
      context of clinical outcome in our center, and were 1.5 times the standard
      deviation (SD) above the mean median channel fluorescence (MCF) of normal sera
      controls. The 1-yr graft survival was 95% for the total group of patients
      studied, and 87% for the recipients who had a positive T cell FCXM. To focus on
      the influence of a positive B cell FCXM on the incidence of rejection, primary
      transplant recipients who had a negative T cell FCXM (n = 81) were studied.
      Fifteen of 30 (50%) recipients with a positive B cell FCXM experienced at least
      one rejection episode within the first year. By contrast, only 15 of 51 (29.4%)
      of patients with a negative B cell FCXM experienced rejection (p = 0.05). The
      mean B cell SMCF in the group of patients who had no rejections was 45 +/- 59,
      while that of the group of patients who experienced at least one rejection was 97
      +/- 97 (p = 0.012). By comparison, the rejection rate among the retransplant
      patients was 44.4%, and the mean B cell SMCF in the group with rejection was 94
      +/- 75 while it was 5 +/- 7 among retransplant patients who did not have
      rejection (p = 0.031). Eighty-six percent of sensitized (panel reactivity
      antibodies (PRA) > 10%) patients who had a B positive/T negative FCXM experienced
      rejection, compared to 33% (n = 6 out of 16) of the B negative/T negative
      sensitized patients (p = 0.03). Furthermore, 62% (n = 13 out of 21) of donor
      recipient mismatched patients with a B positive/T negative FCXM experienced
      rejection, compared to 38% (n = 13 out of 35) of patients with T negative/B
      negative FCXM who were similarly mismatched (p = 0.064). These data demonstrate
      the value of a positive B cell FCXM for predicting post-transplant rejections
      particularly when evaluated in the context of prior sensitization and/or DR
      mismatching. Our results suggest that B cell FCXM may have significant clinical
      implications, justifying its use in post-transplant management of recipients who
      have other risk factors of rejection.

PMID- 10081643
TI  - Intragraft cytokine expression in tolerant rat renal allografts with rapamycin
      and cyclosporin immunosuppression.
AB  - The Th-1/Th-2 paradigm proposes clonal expansion of Th-2 lymphocytes as the basis
      of tolerance towards allografts. Intragraft cytokine expression was evaluated in
      a highly stringent model of renal transplantation. ACI and Lewis rats were used
      as donors and recipients, respectively, for heterotopic renal transplantation.
      Group A (n = 8) received a single dose of rapamycin and cyclosporin 12 h prior to
      engraftment, followed by 7 d of cyclosporin post-operatively. Isografts (Group B,
      n = 5) and control allografts (Group C, n = 4) received no immunosuppression.
      Sacrifice was performed after 120 d. Intragraft expression of IL-10, IL-4, and
      IFN-gamma was determined using qualitative reverse transcriptase-polymerase chain
      reaction (RT-PCR). All groups had functionally normal grafts at sacrifice, with
      50% histological tolerance among Group A animals. No isografts showed evidence of
      cellular infiltrate, and all control allografts showed severe rejection. IL-10
      was only detected in the tolerant animals (p < 0.001). Similarly, IL-4 was
      detected predominantly in the tolerant allografts (p < 0.05). IFN-gamma was only
      isolated in rejected allografts, whether treated or untreated (p < 0.001). We
      conclude that the expansion of Th-2 cells is associated with tolerance, while the
      expansion of Th-1 cell is associated with acute cellular rejection.

PMID- 10081644
TI  - Non-heart-beating cadaver donor hepatectomy 'the operative procedure'.

PMID- 10081645
TI  - Utility of CT angiography for evaluation of living kidney donors.
AB  - We reviewed our initial experience with helical computed tomography (CT)
      angiography in the evaluation of living kidney donors which, until now, has
      necessitated arteriography. Nineteen donors (12 women, 7 men) have had their
      renal anatomy evaluated solely by CT angiography preoperatively. All scans
      demonstrated normal collecting systems and single ureters. Five donors (26%) had
      supernumerary renal arteries. Fourteen donors had single, 4 donors had two, and 1
      donor had three renal arteries. Helical CT demonstrated small polar vessels in
      several donors. Two donors (10%) had supernumerary renal veins. Accuracy of
      vascular anatomy defined on CT was 90% when confirmed at operation. Anatomically
      all CT findings were consistent with operative findings except in 1 donor who was
      found to have a 0.8 cm lesion near the renal hilum. At our institution, the total
      charges for selective renal arteriography are $3845 and for helical CT with three
      dimensional (3-D) reconstruction are $1546. The amount of contrast dye
      (approximately 100 mL) is equivalent. Patients uniformly reported that the CT
      scan was a convenient and painless procedure. The accuracy of helical CT
      angiography is equivalent to arteriography in assessing renal vascular anatomy
      (with the additional benefit of imaging venous and parenchymal anatomy). Charges
      for helical CT are 59% less. There is greater patient acceptance and potentially
      less morbidity associated with the non-invasive nature of helical CT. We believe
      that CT angiography is the radiologic procedure of choice for the assessment of
      renal anatomy in potential living kidney donors.

PMID- 10081646
TI  - Living-unrelated kidney donation: a single-center experience.
AB  - For 140 consecutive renal transplants performed from January 1995 to October
      1997, 25 (18%) were from living-unrelated donors (15 women, 10 men, aged 25-63,
      mean 43 yr). All donors had pre-transplant imaging evaluation of renal anatomy
      following renal function assessment (minimal creatinine clearance 75 cm3/min).
      Admission to the hospital on the day of donation preceded nephrectomy under
      general anesthesia using an anterior flank, extra-retroperitoneal approach (no
      rib resection). Post-operative epidural pain control was used for all but 1
      donor. The 25 kidney donors were hospitalized for 2 (n = 1), 3 (n = 12), 4 (n =
      7), or 5-8 d (n = 5) (average 3.9 d) and had a mean hospitalization charge of
      $15,501 (range $10,808-$29,579). One intra-operative hemorrhage required
      transfusion; 1 late neural-related pain syndrome required outpatient wound
      exploration. Two kidneys were lost: a husband recipient from repetitive acute
      rejections at 3 months; a friend recipient from chronic rejection at 2.5 yr; both
      await cadaver transplant. The other 23 kidneys are functioning with a mean serum
      creatinine of 1.8 (range 1.0-3.3) at 3-36 months (patient survival 100%; graft
      survival 92%). While most donors were spouses (8 husbands and 10 wives), friends,
      distant cousins, in-laws, and adoptive relatives did well as donors and
      recipients. Transplantation may increase by 20% or more at centers which
      encourage broad application of living donor nephrectomy.

PMID- 10081647
TI  - A study of endothelial cell-lymphocyte responses in human renal transplantation.
AB  - Histological studies have demonstrated vascular damage in all types of allograft
      rejection. It is likely that donor endothelium suffers the major and the first
      insult by the recipient's immune system since, in vivo, capillary endothelium
      expresses human lymphocyte antigen (HLA) class I and class II antigens. The
      present study was designed to examine whether injury to donor endothelial cells
      (ECs) by recipient peripheral blood mononuclear cells (PBMCs) can be demonstrated
      in vitro, and whether there is a relationship between the in vitro findings and
      the clinical outcome of renal allografts. Twenty renal transplant recipients were
      included in this study, and all patients were followed up for 6 months. PBMCs
      were isolated from the renal transplant recipients on three occasions; in the
      first 24-h post-transplantation, at the beginning of the second week, and in the
      third week post-transplantation. Additional samples were taken at the time of any
      acute rejection episode. These patients received renal allografts from 15 local
      cadaveric donors whose ECs were isolated. Donor-specific ECs and the
      corresponding renal transplant recipients' PBMCs and sera were employed in
      proliferation and cytotoxicity assays. Our results show that donor-specific ECs
      consistently induced a highly significant degree of recipient lymphocyte
      proliferative response (p < 0.05). However, no significant correlation between
      acute graft rejection and the degree of donor-specific EC-induced recipient
      lymphocyte proliferation was found. In contrast, there was a significant
      correlation between lymphocyte-induced EC cytolytic effects and acute renal graft
      rejection (p < 0.05). When conducted in larger studies, such information can have
      important implications in clinical transplantation.

PMID- 10081648
TI  - Tacrolimus vs Neoral in renal and renal/pancreas transplantation.
AB  - In a retrospective analysis we compared the outcome of a group of 63 kidney or
      kidney/pancreas transplant recipients who were transplanted between June 1994 and
      February 1997 and received either tacrolimus (FK, n = 22) or Neoral (NEO, n = 41)
      as part of a triple immunosuppressive protocol. Ten patients in the NEO group has
      recurrent rejection episodes between 1 and 8 months post-transplant and were
      converted to FK. CellCept was the secondary immunosuppressive agent in about half
      the FK, three-quarters of the NEO, and in all but one in the conversion (CON)
      groups. Patients in all groups were on prednisone in equal amounts. Mean duration
      of follow-up for FK, NEO and CON groups was 32, 19 and 13 months, respectively.
      One-yr patient and graft survival was 100% in all groups. At 2 yr, graft survival
      was 95, 96 and 100% in FK, NEO and CON groups, respectively. Acute rejection at 1
      yr was twice as high in the NEO group as the FK group. There were no rejection
      episodes among the FK patients who also received CellCept. The mean current serum
      creatinines (mg%) were: FK = 1.6, NEO = 1.8, CON = 1.9. Recurrent infection was
      more common with FK (8/22) than NEO (1/31) (p = 0.023). Our experience suggests
      there is less rejection but more infection in recipients treated with FK compared
      to NEO. In patients with recurrent rejection, conversion from NEO to FK
      stabilizes renal function and minimizes subsequent rejection episodes.

PMID- 10081649
TI  - Increased early morbidity and mortality with acceptable long-term function in
      severely obese patients undergoing liver transplantation.
AB  - The effect of obesity on outcomes following liver transplantation remains
      unclear. We reviewed our experience with 302 liver transplants in 277 patients
      from September 1989 to September 1996 to determine the effect of body mass on
      outcome. Two-hundred and seventeen transplants were performed in patients with a
      body mass index (BMI) < 30 kg/m2, 55 in patients with a BMI of 30-34 kg/m2
      (obese), and 30 in patients with a BMI > 35 kg/m2 (severely obese). Non-weight
      related pre-operative demographics were similar between groups with the exception
      of an increased frequency of cryptogenic cirrhosis among the obese and severely
      obese patients. Intra-operative transfusion requirements were greater for the
      severely obese group (16.2 +/- 3.5 units versus 9.1 +/- 0.8 units for the non
      obese, p = 0.0004), though not when normalized to body weight (0.14 +/- 0.03
      units/kg versus 0.13 +/- 0.01 units/kg, p > 0.05). Post-operatively, severely
      obese patients had a higher rate of wound infection (20 versus 4%, p = 0.0001)
      and death attributed to multisystem organ failure (15 versus 2%, p = 0.0001),
      although overall mortality prior to discharge and total complications were not
      different between groups. Actual 1-yr graft survival showed a negative trend in
      the severely obese group (67 versus 81% for non-obese, p = 0.07), but both 3-yr
      graft survival and patient survival were similar to non-obese patients (p = 0.12
      and 0.17, respectively by the Cox-Mantel test). Liver transplantation in severely
      obese patients is associated with wound infection and early death from
      multisystem organ failure, but has similar long-term outcomes when compared to
      non-obese controls.

PMID- 10081650
TI  - Neuron specific enolase in small cell lung cancer. Clinical and biochemical
      evaluation.

PMID- 10081651
TI  - Studies of gene expression and activity of hexokinase, phosphofructokinase and
      glycogen synthase in human skeletal muscle in states of altered insulin
      stimulated glucose metabolism.
AB  - When whole body insulin-stimulated glucose disposal rate is measured in man
      applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown
      that approximately 75% of glucose is taken up by skeletal muscle. After the
      initial transport step, glucose is rapidly phosphorylated to glucose-6-phosphate
      and routed into the major pathways of either glucose storage as glycogen or the
      glycolytic/tricarboxylic acid pathway. Glucose uptake in skeletal muscle involves
      the activity of specific glucose transporters and hexokinases, whereas,
      phosphofructokinase and glycogen synthase hold critical roles in glucose
      oxidation/glycolysis and glucose storage, respectively. Glucose transporters and
      glycogen synthase activities are directly and acutely stimulated by insulin
      whereas the activities of hexokinases and phosphofructokinase may primarily be
      allosterically regulated. The aim of the review is to discuss our present
      knowledge of the activities and gene expression of hexokinase II (HKII),
      phosphofructokinase (PFK) and glycogen synthase (GS) in human skeletal muscle in
      states of altered insulin-stimulated glucose metabolism. My own experimental
      studies have comprised patients with disorders characterized by insulin
      resistance like non-insulin-dependent diabetes mellitus (NIDDM) and insulin
      dependent diabetes mellitus (IDDM) before and after therapeutic interventions,
      patients with microvascular angina and patients with severe insulin resistant
      diabetes mellitus and congenital muscle fiber type disproportion myopathy as well
      as athletes who are in a state of improved insulin sensitivity. By applying the
      glucose insulin clamp method in combination with nuclear magnetic resonance 31P
      spectroscopy to normoglycaemic or hyperglycaemic insulin resistant subjects
      impairment of insulin-stimulated glucose transport and/or phosphorylation in
      skeletal muscle has been shown. In states characterized by insulin resistance but
      normoglycaemia, the activity of HKII measured in needle revealed any genetic
      variability that contributes to explain the decreased muscle levels of GS mRNA or
      the decreased activity and activation of muscle GS in NIDDM patients and their
      glucose tolerant but insulin resistant relatives. Thus, the causes of impaired
      insulin-stimulated glycogen synthesis of skeletal muscle in normoglycaemic
      insulin resistant subjects are likely to be found in the insulin signalling
      network proximal to the GS protein. In insulin resistant diabetic patients the
      impact of these yet unknown abnormalities may be accentuated by the prevailing
      hyperglycaemia and hyperlipidaemia. Endurance training in young healthy subjects
      results in improved insulin-stimulated glucose disposal rates, predominantly due
      to an increased glycogen synthesis rate in muscle, which is paralleled by an
      increased total GS activity, increased GS mRNA levels and enhanced insulin
      stimulated activation of GS. These changes are probably due to local contraction
      dependent mechanisms. Likewise, one-legged exercise training has been reported to
      increase the basal concentration of muscle GS mRNA in NIDDM patients to a level
      similar to that seen in control subjects although insulin-stimulated glucose
      disposal rates remain reduced in NIDDM patients. In the insulin resistant states
      examined so far, basal and insulin-stimulated glucose oxidation rate at the whole
      body level and PFK activity in muscle are normal. In parallel, no changes have
      been found in skeletal muscle levels of PFK mRNA and immunoreactive protein in
      NIDDM or IDDM patients. In endurance trained subjects insulin-stimulated whole
      body glucose oxidation rate is often increased. However, depending on the
      intensity and frequency, physical exercise may induce an increased, a decreased
      or an unaltered level of muscle PFK activity. In athletes the muscle PFK mRNA is
      similar to what is found in sedentary subjects whereas the immunoreactive PFK
      protein concentration is decreased.

PMID- 10081652
TI  - Effects of substance P on cellular signalling systems in the rat anterior
      pituitary.

PMID- 10081653
TI  - Results from screening for gestational diabetes mellitus in a Danish county.
AB  - OBJECTIVE: To examine the complications in gestational diabetes mellitus with
      special reference to the significance of the threshold for the oral glucose
      tolerance test (OGTT, plasma glucose > or = 7.8 mmol/l (equivalent to blood
      glucose 6.9 mmol/l) (WHO criteria) or blood glucose > 6.7 mmol/l (local criteria)
      after 2 h 75 g oral glucose load). DESIGN: Prospective descriptive study.
      SETTING: From April 1, 1995 to April 1, 1997 a screening for gestational diabetes
      mellitus (GDM) according to the recommendations from the Danish board of health
      was performed in Ribe county. SUBJECTS: Pregnant women in Ribe county (n = 6158).
      MAIN OUTCOME MEASURES: Complications during pregnancy and the outcome. RESULTS:
      Two hundred and twenty (3.6%) women had GDM by the local selection criteria and
      2.8% according to the WHO criteria. The study revealed a significantly increased
      frequency of malformations (7.3% vs. 1.2%, p < 0.0001) and preeclampsia (15.5%
      vs. 1%, p < 0.0001) in the group with GDM independent of selection criteria
      (obesity vs. family history and glucosuria). The frequency of preeclampsia
      appeared higher in the group with obesity (p = 0.040). Malformations appeared
      with identical frequency in the groups with OGGT threshold higher than blood
      glucose 6.9 mmol/l (plasma glucose 7.8 mmol/l) (WHO criteria) and with blood
      glucose between 6.7 and 6.9 mmol/l, whereas preeclampsia did not occur with
      higher frequency in the latter group. CONCLUSION: Complications appear frequently
      in women with an abnormal OGGT, and obesity predisposes to preeclampsia. The use
      of the WHO criteria for screening for GDM would miss a number of women with
      complications.

PMID- 10081654
TI  - Guidelines for good scientific practice.
AB  - The Danish Committee on Scientific Dishonesty (DCSD) has existed for five years.
      As a preventive measure two sets of guidelines for the presentation of
      experimental reports and data documentation have been issued. Experiences from 24
      cases of suspected scientific dishonesty have proven a need for further
      guidelines covering a wider range of scientific practice. Three key areas
      susceptible to conflicts between researchers and often resulting in subsequent
      accusations of scientific misconduct have been localized. Guidelines have,
      therefore, been prepared for these three areas: 1) Agreements at the start of
      cooperative research projects. 2) Rights and duties in storing and using research
      data. 3) Authorship. It is hoped that they will be helpful in prevention of
      conflicts and deviations from good scientific practice, and that they will be
      useful in the education of young researchers. The Danish Committee on Scientific
      Dishonesty. The Ministry of Research and Information Technology, Copenhagen.

PMID- 10081655
TI  - Guideline for agreements at the initiation of research projects. Danish Committee
      on Scientific Dishonesty.

PMID- 10081656
TI  - Guidelines on the rights and duties in the storage and use of research data.
      Danish Committee on Scientific Dishonesty.

PMID- 10081657
TI  - Guidelines concerning authorship. Danish Committee on Scientific Dishonesty.

PMID- 10081658
TI  - Effects of pulsed or continuous infusion of cortisol on immune function in sheep.
AB  - It was postulated that frequent pulses of cortisol such as might be induced by a
      repeated or chronic stressor, could induce immune suppression and that the effect
      would be greater than in animals subjected to less frequent increases. Four
      groups of nine adult Scottish Blackface ewes were infused for 14 d with saline or
      hydrocortisone hemisuccinate (cortisol) delivered continuously or in pulses.
      Plasma concentrations of cortisol were significantly elevated (to between
      approximately 100 and 1000 nmol/liter; P < 0.001) for about 30 or 75 min after
      infusion of pulses of hydrocortisone hemisuccinate at intervals of 1 hr (P1) or 6
      hr (P6), respectively. In animals continuously infused (CI), they were
      consistently elevated (P < 0.001), compared with concentrations in control
      animals infused with saline only (S), to approximately 1000 nmol/liter or more.
      Antibody production in response to ovalbumin injection was not affected by any of
      the infusion regimes. At Days 10, 24, and 31 after injection of ovalbumin and
      initiation of the infusion, rates of multiplication of unstimulated lymphocytes,
      in vitro, were greater (P < 0.05) in P6 animals than in saline-infused, control
      animals and this resulted in a reduction in the stimulated lymphocyte response.
      As a consequence of the increased basal lymphocyte activity, after Day 0, the
      corrected, stimulated lymphocyte response of P6 animals was consistently below
      that of controls (P < 0.05 at Day 24). Both mean basal and stimulated lymphocyte
      activities in CI and P1 animals were similar to those of controls. The gamma
      interferon (IFN-gamma) response was generally small and not affected by
      treatment. It is concluded that large, relatively infrequent increases in
      circulating cortisol concentrations can modify the cell mediated immune response
      such that the response to a specific antigen challenge is compromised but
      smaller, more frequent pulses had no effect. Elevated cortisol concentrations per
      se did not have a significant inhibitory effect on the immune system.

PMID- 10081659
TI  - Diagnostic utility of glycosylated hemoglobin concentrations in the cat.
AB  - Changes in glycosylated hemoglobin (GHb) concentrations, K values (%
      disappearance of glucose/min after an intravenous injection of 1 g/kg dextrose),
      and blood glucose concentrations were examined in eight cats before and during
      the induction of diabetes, and in four of these cats after they were placed on
      insulin treatment. There was a statistically significant separation of GHb, K
      values, and fasting blood glucose concentrations between healthy and diabetic
      cats. Changes in GHb correlated best with the K value and single weekly fasting
      glucose concentrations averaged over eight periods for each cat while diabetes
      was induced (R = 0.80 and 0.78, respectively); however, fasting blood glucose
      concentrations obtained on the day of the GHb measurement were also highly
      correlated (R = 0.69; P < 0.001). The correlation between GHb and single weekly
      glucose concentrations obtained in insulin-treated cats at the time of insulin
      peak action and averaged over an 8-wk time period for each cat was less but still
      significant (R = 0.53; P < 0.001). It is concluded that GHb measurements are a
      simple and reliable way to monitor changes in glucose control in the diabetic cat
      over a prolonged period.

PMID- 10081660
TI  - Insulin-like growth factor binding protein-3: its biological effect on bovine
      granulosa cells.
AB  - This study was aimed at testing the hypothesis that insulin-like growth factor
      binding protein (IGFBP)-3 can modulate hormone-dependent differentiation of
      granulosa cells in vitro. Granulosa cells from small (1 to 5 mm) follicles were
      collected from cattle, cultured for 2 d in medium containing 10% fetal calf
      serum, washed, and then treated for an additional 2 d in serum-free medium with
      follicle-stimulating hormone (FSH) (50 ng/ml), recombinant human IGF-I (0, 1.3,
      4.0, or 13.3 nM), or recombinant human IGFBP-3 (0 to 4.26 nM). In one series of
      experiments, IGFBP-3 (0.53 and 2.13 nM) inhibited (51% to 92% decreases; P <
      0.05) progesterone and estradiol production induced by 1.3 nM of IGF-I, but did
      not influence (P > 0.10) granulosa cell numbers or steroidogenesis in the absence
      of IGF-I. Only 4.26 nM of IGFBP-3 inhibited (by 35%) the increase in granulosa
      cell numbers induced by 1.3 nM of IGF-I. In another series of experiments, 13.3
      nM of IGF-I, but not 4.0 nM of IGF-I, was able to completely overcome the
      inhibitory effect of 4.26 nM of IGFBP-3 on estradiol production. The increase in
      cell numbers induced by 4.0 and 13.3 nM of IGF-I was attenuated (P < 0.001) by
      4.26 nM of IGFBP-3. In a third series of experiments, IGFBP-3 inhibited 125I-IGF
      I binding to granulosa cells. These results indicate that IGFBP-3 has a
      pronounced inhibitory effect on IGF-I action in cultured bovine granulosa cells,
      and that this inhibitory effect is likely attributable to IGFBP-3
      binding/sequestering IGF-I. Thus, IGFBP-3 may play a significant role in
      regulating granulosa cell proliferation and steroidogenesis during follicular
      development in cattle.

PMID- 10081661
TI  - Oral administration of peptidergic growth hormone (GH) secretagogue KP102
      stimulates GH release in goats.
AB  - To assess the oral activity of KP102 (also known GHRP-2) on growth hormone (GH)
      release in ruminant animals, 5 or 10 mg/kg body weight (BW) of KP102 dissolved in
      saline was orally administered twice at 2 hr-intervals to either 1- or 3-mo-old
      goats (n = 5-6). Plasma GH concentrations in the 1-mo-old goats were elevated at
      15 min after the first administration of both 5 and 10 mg/kg BW of KP102.
      Significant elevation of GH concentrations continued until 180 min after 10 mg/kg
      BW of KP102, whereas the elevated GH levels after the administrations of 5 mg/kg
      BW of KP102 subsided to basal concentrations within 90 min. The second
      administration of 10 mg/kg BW of KP102 failed to elevate the GH concentration,
      but 5 mg/kg BW of KP102 abruptly stimulated GH release. Plasma GH concentrations
      in the 3-mo-old goats were also significantly elevated after the administration
      of both 5 and 10 mg/kg BW of KP102. The plasma GH responses to 5 and 10 mg/kg BW
      of KP102 were almost identical. The elevated GH levels after the first
      administration of KP102 tended to be maintained throughout the experiment, and a
      transient increase in plasma GH levels was observed after the second
      administration. However, the stimulatory effect of KP102 on GH release in the 3
      mo-old goats was small and less abrupt than that in the 1-mo-old goats. The
      concentrations of insulin-like growth factor-I were not increased by KP102 during
      the brief sampling periods used in this experiment. These results show that the
      oral administration of the peptidergic GH secretogogue KP102 stimulates GH
      release in a ruminant species, and that the oral activity of KP102 on GH release
      is modified by the age.

PMID- 10081662
TI  - Circadian and ultradian rhythms of body temperature and peripheral concentrations
      of insulin and nitrogen in lactating dairy cows.
AB  - To investigate possible circadian and ultradian periodicities for peripheral
      insulin and urea in lactating dairy cows, integrated 15-min blood samples were
      taken sequentially over 48 hr from six cows. In addition, radiotelemetry
      measurements of body temperature were averaged over the same 15-min periods. Cows
      were housed in an environmental chamber at 19 degrees C with lights on 0700 to
      2300 hr; fed daily at 0900 hr; and milked at 0800 and 2000 hr. For five of the
      six cows, body temperature showed a circadian rhythm peaking at 2323 hr with an
      amplitude of 0.34 degree C. For the sixth cow, body temperature was 180 degrees
      out-of-phase, peaking at 1230 hr with an amplitude of 0.12 degree C. Circadian
      rhythms for insulin and urea were consistent for all six cows peaking at 1743 hr
      with an amplitude of 0.74 ng/ml for insulin and at 1034 hr with an amplitude of
      3.83 mM for urea. Body temperature and insulin also displayed episodic increases
      that often exceeded the amplitudes of circadian rhythms. For body temperature, a
      broad increase in spectral power was seen for periods between 100 and 175 min;
      time intervals between peaks averaged around 100 min. For insulin, power spectra
      for individual cows universally indicated rhythms with periods of approximately
      45 and 80 min; time intervals between peaks averaged approximately 65 min. For
      urea, almost all spectral energy was confined to the 24-hr rhythm, although there
      was evidence of a low-amplitude, 60-min rhythm. In conclusion, when animals are
      acclimated to a rigidly controlled environment and frequent blood sampling is
      accomplished with minimal intervention, it is possible to detect rhythms inherent
      in the regulation of metabolic variables.

PMID- 10081663
TI  - The effects of equine somatotropin (eST) on follicular development and
      circulating plasma hormone profiles in cyclic mares treated during different
      stages of the estrous cycle.
AB  - The effects of exogenous equine somatotropin (eST) administration on ovarian
      activity and plasma hormone levels were evaluated on horse and pony mares. The
      objectives of this study were to determine the effects of eST on follicular
      development and circulating concentrations of leutinizing hormone (LH),
      estradiol, progesterone, and insulin-like growth factor I (IGF-I) in cyclic horse
      and pony mares. Sixteen mares received daily injections (i.m.) of eST at a
      concentration of 25 micrograms/kg body weight on either Days 6 through 12
      (Treatment A) or 13 through 19 (Treatment B) postovulation. In addition,
      contemporary mares were similarly given the carrier vehicle and served as
      controls (Treatments C and D). Blood samples were collected at 24-hr intervals
      and ultrasonographic evaluations were performed on the ovaries of each mare at 48
      hr intervals beginning on the first day of treatment and ending either on the day
      of ovulation or 5 d postovulation. Circulating levels of insulin-like growth
      factor-I (IGF-I) were increased in treated mares by Day 3 post-treatment (P <
      0.05). Also, mares in Treatment B exhibited a decrease in plasma estradiol
      concentrations (P < 0.05) when compared with control mares on Days 1 through 5
      postovulation of the post-treated estrous cycle. In addition, circulating
      leutinizing hormone levels were different for mares in Treatment A compared with
      controls on Days--8 through--1 pre-ovulation (P < 0.05). All follicles present on
      the ovaries of each mare were measured and placed into one of five categories
      based on their diameter. Neither the mean number of follicles per size category >
      or = 8 mm in diameter nor the mean follicular diameter within each size category
      differed among treatment and control mares. However, eST treatment significantly
      increased the number of follicles < or = 7 mm on the ovaries of mares treated
      early in the estrous cycle when compared with control mares on Days 3 and 7 post
      treatment and at the onset of standing estrus.

PMID- 10081664
TI  - Effect of exogenous FSH on ovulation rate in homozygous carriers or noncarriers
      of the Booroola FecB gene after hypothalamic-pituitary disconnection or after
      treatment with a GnRH agonist.
AB  - We have tested the hypothesis "that the ovulation rate in homozygous carriers
      (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the
      plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes
      were similar." For this purpose we used two experimental animal models: 1) the
      hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH
      agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment,
      the animals had low plasma concentrations of gonadotropins and were anovulatory.
      In both animal models, BB and +2 ewes were treated with exogenous pregnant mares
      serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory
      follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation.
      HPD or Deslorelin-treated animals administered with pregnant mares serum
      gonadotropin without FSH followed by human chorionic gonadotropin failed to
      ovulate. However for both animal models, the proportion of BB and +2 ewes
      ovulating to various doses of FSH differed such that significantly greater
      proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When
      HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of
      FSH, the mean ovulation rate and plasma concentrations of FSH in those animals
      which ovulated was the same in both genotypes. These findings confirm, at least
      in part, the aforementioned hypothesis. The results also demonstrated that higher
      ovulation rates were obtained in both genotypes as the FSH dose was increased.
      Collectively, these findings infer that the higher mean ovulation rate in normal
      intact BB ewes compared to the +2 genotype is attributable to effects of the FecB
      gene at the level of ovarian follicular development as well as at the level of
      pituitary FSH release.

PMID- 10081665
TI  - Effect of bursal antisteroidogenic peptide (BASP) on chicken embryonic pituitary
      secretion of growth hormone (GH) and prolactin (PRL): evaluation in a reverse
      hemolytic plaque assay (RHPA).
AB  - Using the reverse hemolytic plaque assay described in the present investigation,
      a secretagogue activity of bursal antisteroidogenic peptide (BASP) for growth
      hormone (GH) or prolactin (PRL) secretion was observed in chicken Day 20e
      pituitary cell monolayers. Partially purified BASP (ppBASP), at all
      concentrations evaluated (0.25 BEQ/ml, 0.75 BEQ/ml, or 1.5 BEQ/ml), induced PRL
      secretion by isolated lactotrophs above (P < 0.05) basal levels during the 2- and
      6-hr incubation. At the 18-hr time point, neither ppBASP nor vasoactive
      intestinal polypeptide (VIP) was efficacious (P < 0.05) in causing an elevation
      in PRL-secreting cells above basal levels. ppBASP, at all concentrations
      evaluated (0.25 BEQ/ml, 0.75 BEQ/ml, or 1.5 BEQ/ml), caused an increase in the
      percentage of GH-secreting cells above (P < 0.05) basal levels during the 18-hr
      incubation. When evaluating the 2-hr time point alone, ppBASP, at 0.75 or 1.5
      BEQ/ml, significantly (P < 0.05) elevated the percentage of GH-secreting cells to
      above basal levels. After the 6-hr incubation, ppBASP at 0.25 or 0.75 BEQ/ml, was
      efficacious in causing elevated (P < 0.05) GH secretion above basal levels. The
      present study indicates a secretagogue activity of BASP on PRL or GH secretion by
      chicken embryonic anterior pituitary cells in vitro.

PMID- 10081666
TI  - Emerging viral diseases: an Australian perspective.

PMID- 10081667
TI  - The economic impact of Staphylococcus aureus infection in New York City
      hospitals.
AB  - We modeled estimates of the incidence, deaths, and direct medical costs of
      Staphylococcus aureus infections in hospitalized patients in the New York City
      metropolitan area in 1995 by using hospital discharge data collected by the New
      York State Department of Health and standard sources for the costs of health
      care. We also examined the relative impact of methicillin-resistant versus 
      sensitive strains of S. aureus and of community-acquired versus nosocomial
      infections. S. aureus-associated hospitalizations resulted in approximately twice
      the length of stay, deaths, and medical costs of typical hospitalizations;
      methicillin-resistant and -sensitive infections had similar direct medical costs,
      but resistant infections caused more deaths (21% versus 8%). Community-acquired
      and nosocomial infections had similar death rates, but community-acquired
      infections appeared to have increased direct medical costs per patient ($35,300
      versus $28,800). The results of our study indicate that reducing the incidence of
      methicillin-resistant and -sensitive nosocomial infections would reduce the
      societal costs of S. aureus infection.

PMID- 10081668
TI  - Socioeconomic and behavioral factors leading to acquired bacterial resistance to
      antibiotics in developing countries.
AB  - In developing countries, acquired bacterial resistance to antimicrobial agents is
      common in isolates from healthy persons and from persons with community-acquired
      infections. Complex socioeconomic and behavioral factors associated with
      antibiotic resistance, particularly regarding diarrheal and respiratory
      pathogens, in developing tropical countries, include misuse of antibiotics by
      health professionals, unskilled practitioners, and laypersons; poor drug quality;
      unhygienic conditions accounting for spread of resistant bacteria; and inadequate
      surveillance.

PMID- 10081669
TI  - Campylobacter jejuni--an emerging foodborne pathogen.
AB  - Campylobacter jejuni is the most commonly reported bacterial cause of foodborne
      infection in the United States. Adding to the human and economic costs are
      chronic sequelae associated with C. jejuni infection--Guillian-Barre syndrome and
      reactive arthritis. In addition, an increasing proportion of human infections
      caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw
      poultry and consumption of undercooked poultry are the major risk factors for
      human campylobacteriosis. Efforts to prevent human illness are needed throughout
      each link in the food chain.

PMID- 10081670
TI  - Comparative genomics and host resistance against infectious diseases.
AB  - The large size and complexity of the human genome have limited the identification
      and functional characterization of components of the innate immune system that
      play a critical role in front-line defense against invading microorganisms.
      However, advances in genome analysis (including the development of comprehensive
      sets of informative genetic markers, improved physical mapping methods, and novel
      techniques for transcript identification) have reduced the obstacles to discovery
      of novel host resistance genes. Study of the genomic organization and content of
      widely divergent vertebrate species has shown a remarkable degree of evolutionary
      conservation and enables meaningful cross-species comparison and analysis of
      newly discovered genes. Application of comparative genomics to host resistance
      will rapidly expand our understanding of human immune defense by facilitating the
      translation of knowledge acquired through the study of model organisms. We review
      the rationale and resources for comparative genomic analysis and describe three
      examples of host resistance genes successfully identified by this approach.

PMID- 10081671
TI  - Cyclospora: an enigma worth unraveling.
AB  - In part, Cyclospora cayetanensis owes its recognition as an emerging pathogen to
      the increased use of staining methods for detecting enteric parasites such as
      Cryptosporidium. First reported in patients in New Guinea in 1977 but thought to
      be a coccidian parasite of the genus Isospora, C. cayetanensis received little
      attention until it was again described in 1985 in New York and Peru. In the early
      1990s, human infection associated with waterborne transmission of C. cayetanensis
      was suspected; foodborne transmission was likewise suggested in early studies.
      The parasite was associated with several disease outbreaks in the United States
      during 1996 and 1997. This article reviews current knowledge about C.
      cayetanensis (including its association with waterborne and foodborne
      transmission), unresolved issues, and research needs.

PMID- 10081672
TI  - Using monoclonal antibodies to prevent mucosal transmission of epidemic
      infectious diseases.
AB  - Passive immunization with antibodies has been shown to prevent a wide variety of
      diseases. Recent advances in monoclonal antibody technology are enabling the
      development of new methods for passive immunization of mucosal surfaces. Human
      monoclonal antibodies, produced rapidly, inexpensively, and in large quantities,
      may help prevent respiratory, diarrheal, and sexually transmitted diseases on a
      public health scale.

PMID- 10081673
TI  - Dual and recombinant infections: an integral part of the HIV-1 epidemic in
      Brazil.
AB  - We systematically evaluated multiple and recombinant infections in an HIV
      infected population selected for vaccine trials. Seventy-nine HIV-1 infected
      persons in a clinical cohort study in Rio de Janeiro, Brazil, were evaluated for
      1 year. A combination of molecular screening assays and DNA sequencing showed 3
      dual infections (3.8%), 6 recombinant infections (7.6%), and 70 (88.6%)
      infections involving single viral subtypes. In the three dual infections, we
      identified HIV-1 subtypes F and B, F and D, and B and D; in contrast, the single
      and recombinant infections involved only HIV-1 subtypes B and F. The recombinants
      had five distinct B/F mosaic patterns: Bgag-p17/Bgag-p24/Fpol/Benv, Fgag-p17/Bgag
      p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Benv, and
      Fgag-p17/B-Fgag-p24/Fpol/Fenv. No association was found between dual or
      recombinant infections and demographic or clinical variables. These findings
      indicate that dual and recombinant infections are emerging as an integral part of
      the HIV/AIDS epidemic in Brazil and emphasize the heterogenous character of
      epidemics emerging in countries where multiple viral subtypes coexist.

PMID- 10081674
TI  - Genetic diversity and distribution of Peromyscus-borne hantaviruses in North
      America.
AB  - The 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern
      United States was associated with Sin Nombre virus, a rodent-borne hantavirus;
      The virus' primary reservoir is the deer mouse (Peromyscus maniculatus).
      Hantavirus-infected rodents were identified in various regions of North America.
      An extensive nucleotide sequence database of an 139 bp fragment amplified from
      virus M genomic segments was generated. Phylogenetic analysis confirmed that SNV
      like hantaviruses are widely distributed in Peromyscus species rodents throughout
      North America. Classic SNV is the major cause of HPS in North America, but other
      Peromyscine-borne hantaviruses, e.g., New York and Monongahela viruses, are also
      associated with HPS cases. Although genetically diverse, SNV-like viruses have
      slowly coevolved with their rodent hosts. We show that the genetic relationships
      of hantaviruses in the Americas are complex, most likely as a result of the rapid
      radiation and speciation of New World sigmodontine rodents and occasional virus
      host switching events.

PMID- 10081675
TI  - Climatic and environmental patterns associated with hantavirus pulmonary
      syndrome, Four Corners region, United States.
AB  - To investigate climatic, spatial, temporal, and environmental patterns associated
      with hantavirus pulmonary syndrome (HPS) cases in the Four Corners region, we
      collected exposure site data for HPS cases that occurred in 1993 to 1995. Cases
      clustered seasonally and temporally by biome type and geographic location, and
      exposure sites were most often found in pinyon-juniper woodlands, grasslands, and
      Great Basin desert scrub lands, at elevations of 1,800 m to 2,500 m.
      Environmental factors (e.g., the dramatic increase in precipitation associated
      with the 1992 to 1993 El Nino) may indirectly increase the risk for Sin Nombre
      virus exposure and therefore may be of value in designing disease prevention
      campaigns.

PMID- 10081676
TI  - Long-term studies of hantavirus reservoir populations in the southwestern United
      States: rationale, potential, and methods.
AB  - Hantaviruses are rodent-borne zoonotic agents that cause hemorrhagic fever with
      renal syndrome in Asia and Europe and hantavirus pulmonary syndrome (HPS) in
      North and South America. The epidemiology of human diseases caused by these
      viruses is tied to the ecology of the rodent hosts, and effective control and
      prevention relies on a through understanding of host ecology. After the 1993 HPS
      outbreak in the southwestern United States, the Centers for Disease Control and
      Prevention initiated long-term studies of the temporal dynamics of hantavirus
      infection in host populations. These studies, which used mark-recapture
      techniques on 24 trapping webs at nine sites in the southwestern United States,
      were designed to monitor changes in reservoir population densities and in the
      prevalence and incidence of infection; quantify environmental factors associated
      with these changes; and when linked to surveillance databases for HPS, lead to
      predictive models of human risk to be used in the design and implementation of
      control and prevention measures for human hantavirus disease.

PMID- 10081677
TI  - Long-term hantavirus persistence in rodent populations in central Arizona.
AB  - For 35 months, we monitored hantavirus activity in rodent populations in central
      Arizona. The most frequently captured hantavirus antibody-positive rodents were
      Peromyscus boylii and P. truei. Antibody-positive P. boylii were more frequently
      male (84%), older, and heavier, and they survived longer on trapping web sites
      than antibody-negative mice. The number of antibody-positive P. boylii was
      greater during high population densities than during low densities, while
      antibody prevalence was greater during low population densities. Virus
      transmission and incidence rates, also related to population densities, varied by
      trapping site. The spatial distribution of antibody-positive P. boylii varied by
      population density and reflected the species preference for dense chaparral
      habitats. The focal ranges of antibody-positive P. boylii also demonstrated a
      patchy distribution of hantavirus.

PMID- 10081678
TI  - A longitudinal study of Sin Nombre virus prevalence in rodents, southeastern
      Arizona.
AB  - We determined the prevalence of Sin Nombre virus antibodies in small mammals in
      southeastern Arizona. Of 1,234 rodents (from 13 species) captured each month from
      May through December 1995, only mice in the genus Peromyscus were seropositive.
      Antibody prevalence was 14.3% in 21 white-footed mice (P. leucopus), 13.3% in 98
      brush mice (P. boylii), 0.8% in 118 cactus mice (P. eremicus), and 0% in 2 deer
      mice (P. maniculatus). Most antibody-positive mice were adult male Peromyscus
      captured close to one another early in the study. Population dynamics of brush
      mice suggest a correlation between population size and hantavirus-antibody
      prevalence.

PMID- 10081679
TI  - Statistical sensitivity for detection of spatial and temporal patterns in rodent
      population densities.
AB  - A long-term monitoring program begun 1 year after the epidemic of hantavirus
      pulmonary syndrome in the U.S. Southwest tracked rodent density changes through
      time and among sites and related these changes to hantavirus infection rates in
      various small-mammal reservoir species and human disease outbreaks. We assessed
      the statistical sensitivity of the program's field design and tested for
      potential biases in population estimates due to unintended deaths of rodents.
      Analyzing data from two sites in New Mexico from 1994 to 1998, we found that for
      many species of Peromyscus, Reithrodontomys, Neotoma, Dipodomys, and Perognathus,
      the monitoring program detected species-specific spatial and temporal differences
      in rodent densities; trap-related deaths did not significantly affect long-term
      population estimates. The program also detected a short-term increase in rodent
      densities in the winter of 1997-98, demonstrating its usefulness in identifying
      conditions conducive to increased risk for human disease.

PMID- 10081680
TI  - Natural history of Sin Nombre virus in western Colorado.
AB  - A mark-recapture longitudinal study of immunoglobulin G (IgG) antibody to Sin
      Nombre virus (SNV) in rodent populations in western Colorado (1994-results
      summarized to October 1997) indicates the presence of SNV or a closely related
      hantavirus at two sites. Most rodents (principally deer mice, Peromyscus
      maniculatus, and pinyon mice, P. truei) did not persist on the trapping webs much
      beyond 1 month after first capture. Some persisted more than 1 year, which
      suggests that even a few infected deer mice could serve as transseasonal
      reservoirs and mechanisms for over-winter virus maintenance. A positive
      association between wounds and SNV antibody in adult animals at both sites
      suggests that when infected rodents in certain populations fight with uninfected
      rodents, virus amplification occurs. At both sites, male rodents comprised a
      larger percentage of seropositive mice than recaptured mice, which suggests that
      male mice contribute more to the SNV epizootic cycle than female mice. In deer
      mice, IgG antibody prevalence fluctuations were positively associated with
      population fluctuations. The rates of seroconversion, which in deer mice at both
      sites occurred mostly during late summer and midwinter, were higher than the
      seroprevalence, which suggests that the longer deer mice live, the greater the
      probability they will become infected with SNV.

PMID- 10081681
TI  - Long-term studies of hantavirus reservoir populations in the southwestern United
      States: a synthesis.
AB  - A series of intensive, longitudinal, mark-recapture studies of hantavirus
      infection dynamics in reservoir populations in the southwestern United States
      indicates consistent patterns as well as important differences among sites and
      host-virus associations. All studies found a higher prevalence of infection in
      older (particularly male) mice; one study associated wounds with seropositivity.
      These findings are consistent with horizontal transmission and transmission
      through fighting between adult male rodents. Despite very low rodent densities at
      some sites, low-level hantavirus infection continued, perhaps because of
      persistent infection in a few long-lived rodents or periodic reintroduction of
      virus from neighboring populations. Prevalence of hantavirus antibody showed
      seasonal and multiyear patterns that suggested a delayed density-dependent
      relationship between prevalence and population density. Clear differences in
      population dynamics and patterns of infection among sites, sampling periods, and
      host species underscore the importance of replication and continuity of long-term
      reservoir studies. Nevertheless, the measurable associations between
      environmental variables, reservoir population density, rates of virus
      transmission, and prevalence of infection in host populations may improve our
      capacity to model processes influencing infection and predict increased risk for
      hantavirus transmission to humans.

PMID- 10081682
TI  - Proficiency of clinical laboratories in and near Monterrey, Mexico, to detect
      vancomycin-resistant enterococci.
AB  - Early detection of vancomycin-resistant enterococci is important for preventing
      its spread among hospitalized patients. We surveyed the ability of eight hospital
      laboratories in and near Monterrey, Mexico, to detect vancomycin resistance in
      Enterococcus spp. and found that although laboratories can reliably detect high
      level vancomycin resistance, many have difficulty detecting low-level resistance.

PMID- 10081683
TI  - Staphylococcus aureus with reduced susceptibility to vancomycin isolated from a
      patient with fatal bacteremia.
AB  - A Staphylococcus aureus isolate with reduced susceptibility to vancomycin was
      obtained from a dialysis patient with a fatal case of bacteremia. Comparison of
      the isolate with two methicillin-resistant S. aureus (MRSA) isolated obtained
      from the same patient 4 months earlier suggests that the S. aureus with reduced
      susceptibility to vancomycin emerged from the MRSA strain with which the patient
      was infected. Atypical phenotypic characteristics, including weak or negative
      latex-agglutination test results, weak or negative-slide coagulase test results,
      heterogeneous morphologic features, slow rate of growth, and vancomycin
      susceptibility (by disk diffusion test) were observed.

PMID- 10081684
TI  - Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia
      and bone marrow transplantation.
AB  - The recently described species Candida dubliniensis has been recovered primarily
      from superficial oral candidiasis in HIV-infected patients. No clinically
      documented invasive infections were reported until now in this patient group or
      in other immunocompromised patients. We report three cases of candidemia due to
      this newly emerging Candida species in HIV-negative patients with chemotherapy
      induced immunosuppression and bone marrow transplantation.

PMID- 10081685
TI  - Household transmission of Streptococcus pneumoniae, Alberta, Canada.

PMID- 10081686
TI  - Preventing zoonotic diseases in immunocompromised persons: the role of physicians
      and veterinarians.
AB  - We surveyed physicians and veterinarians in Wisconsin about the risk for and
      prevention of zoonotic diseases in immunocompromised persons. We found that
      physicians and veterinarians hold significantly different views about the risks
      posed by certain infectious agents and species of animals and communicate very
      little about zoonotic issues; moreover, physicians believe that veterinarians
      should be involved in many aspects of zoonotic disease prevention, including
      patient education.

PMID- 10081687
TI  - Mycoplasma penetrans bacteremia and primary antiphospholipid syndrome.
AB  - Mycoplasma penetrans, a rare bacterium so far only found in HIV-infected persons,
      was isolated in the blood and throat of a non-HIV-infected patient with primary
      antiphospholipid syndrome (whose etiology and pathogenesis are unknown).

PMID- 10081688
TI  - Infectious diarrhea in tourists staying in a resort hotel.
AB  - An outbreak of infectious diarrhea with 70 laboratory-confirmed cases (58 with
      Giardia lamblia) and 107 probable cases occurred in U.K. tourists who stayed in a
      hotel in Greece. After a cluster of six cases in persons who had stayed at the
      hotel was reported, the Communicable Disease Surveillance Centre began active
      case ascertainment. This outbreak illustrates the value of an approach to
      surveillance that integrates routine surveillance data with active case
      ascertainment.

PMID- 10081689
TI  - A midcourse assessment of hantavirus pulmonary syndrome.

PMID- 10081690
TI  - Navigational instinct: a reason not to live trap deer mice in residences.

PMID- 10081691
TI  - Bartonella quintana in body lice collected from homeless persons in Russia.

PMID- 10081692
TI  - Tick-transmitted infections in Transvaal: consider Rickettsia africae.

PMID- 10081693
TI  - Extended-spectrum beta-lactamase-producing Salmonella enteritidis in Trinidad and
      Tobago.

PMID- 10081694
TI  - New emm (M protein gene) sequences of group A streptococci isolated from
      Malaysian patients.

PMID- 10081695
TI  - Mutant chemokine receptor (CCR-5) and its relevance to HIV infection in Arabs.

PMID- 10081696
TI  - Effect of leuprorelin acetate on cell growth and prostate-specific antigen gene
      expression in human prostatic cancer cells.
AB  - OBJECTIVES: We investigated modulation of cell growth and prostate-specific
      antigen (PSA) gene expression in prostatic cancer cells by the luteinizing
      hormone-releasing hormone analog (LH-RHa), leuprorelin acetate, alone or combined
      with other agents. METHODS: The effect of the analog on proliferation of both
      androgen-sensitive and -insensitive prostate cancer cells, maintained in
      different culture conditions, was evaluated by cell counts at various intervals
      of time. Basal expression of PSA gene and its variations were determined by a
      reverse transcriptase-polymerase chain reaction assay. RESULTS: LH-RHa is
      ineffective in regulating cell growth, when used alone in both hormone-sensitive
      and -insensitive cell lines. Nevertheless, it counteracts the stimulatory action
      of androgens on proliferation of LNCaP cells, which respond to low concentrations
      of dihydrotestosterone. Moreover, LH-RHa has an inhibitory effect on the
      mitogenic action of epidermal growth factor (EGF) in androgen-unresponsive PC-3
      cells. The analog reduces PSA gene expression in both hormone-sensitive and 
      insensitive cells. Interestingly, it counteracts the gene expression induced by
      androgens in LNCaP cells and by EGF in PC-3 cells. CONCLUSIONS: These data show
      that LH-RHa may behave like a negative growth factor, which directly regulates
      cell growth and PSA gene expression. Moreover, our findings support the idea that
      growth factors may interfere with the androgen signalling pathway.

PMID- 10081697
TI  - Therapeutic options in locally defined or advanced prostate cancer.
AB  - OBJECTIVE: Critical discussion of the available therapeutic options in locally
      defined or advanced prostate cancer (PCa) in the absence of standards or
      guidelines. METHODS: Medline-based survey of the pertinent literature. The
      therapeutic options are presented stage-by-stage. RESULTS: Intracapsular PCa (T1a
      T2bN0M0) is preferably managed by radical prostatectomy; 'insignificant' cancers
      may be treated expectantly. The outcome of irradiation is not as predictable as
      radical surgery. The following points regarding treatment of locally advanced PCa
      are still under debate: neoadjuvant treatment is probably not as efficient as
      believed; technical refinements of radical prostatectomy may be helpful; in some
      instances, the value of adjuvant treatment is undecided. The efficacy of
      irradiation in conjunction with androgen deprivation probably equals the efficacy
      of surgery. No consensus can be found in the presence of positive lymph nodes,
      although single institutions achieve remarkable results with surgery plus
      androgen deprivation. CONCLUSION: Prognostic factors beside the clinical stages
      and grades should be incorporated in the treatment decision, and quality-of-life
      measurement should gain more importance when the treatment outcome is assessed.

PMID- 10081698
TI  - Role of neoadjuvant treatment in clinically confined prostate cancer. Takeda NHT
      Italian Group.
AB  - OBJECTIVE: This prospective, randomized, multicenter comparative trial studied
      the effect of neoadjuvant hormonal treatment (NHT) prior to radical,
      prostatectomy. METHODS: Histopathologic tissue specimens were obtained from 91
      consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for
      stage B prostate adenocarcinoma. The patients had received NHT for three months.
      Specimens were compared with those from 48 age-matched control patients who
      underwent similar surgery for stage B disease without receiving preoperative
      therapy. RESULTS: Treated tumors with an acinar pattern were distinguishable from
      the untreated tumors by neoplastic acini that appeared shrunken and areas of
      individual infiltrating tumor cells separated by an abundant interglandular
      connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear
      shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and
      enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic
      figures were seen in any treated tumors. CONCLUSIONS: Preliminary results show a
      benefit for patients receiving NHT in regard to the histologic indicators that we
      evaluated.

PMID- 10081699
TI  - Adjuvant hormonal treatment with radiotherapy for locally advanced prostate
      cancer.
AB  - OBJECTIVES: Long-term results of radiotherapy in locally advanced prostate cancer
      are poor due to local and distant failures. Since prostate cancer is hormone
      dependent, tumor androgen deprivation may enhance tumor eradication. METHODS:
      Three randomized phase III trials, RTOG and EORTC are reported: they assess
      androgen suppression by using a luteinizing hormone-releasing hormone analogue
      (LH-RHa) with or without androgen blockade before and during, or during and after
      external irradiation. RESULTS: A gain in disease-free, local relapse-free and
      metastasis-free survival has been obtained (p < 0.001). Only the EORTC 22863
      trial has reported a significant improvement in overall survival (p = 0.001) with
      an LH-RHa started the first day of radiotherapy and administered every 4 weeks
      over 3 years. In the RTOG 85-10 trial, and LH-RHa, initiated in the last week of
      radiation therapy and continued until relapse, increased overall survival only in
      patients with poorly differentiated tumor with a Gleason score of 8-10 (p =
      0.03). CONCLUSION: Androgen suppression prior to and during radiation improves
      disease-free survival; adjuvant hormonal therapy with an LH-RHa during and after
      radiation improves overall survival.

PMID- 10081700
TI  - Intermittent complete androgen blockade in PSA relapse after radical
      prostatectomy and incidental prostate cancer.
AB  - OBJECTIVES: To determine the efficacy, safety and feasibility of intermittent
      androgen deprivation (IAD) in patients with prostate-specific antigen (PSA)
      relapse after radical prostatectomy or with an incidental prostate cancer (pT1B)
      after transurethral resection of the prostate (TURP). METHODS: Open,
      nonrandomized, prospective pilot study using the luteinizing hormone-releasing
      hormone analogue (LH-RHa), leuprorelin acetate (1-month depot) and cyproterone
      acetate. RESULTS: Forty-four patients have been enrolled. After a 30-64 months'
      follow-up no progression to androgen-independent status has been observed. Of the
      entire observation period, 26.6 months (44-58%) remained treatment-free. During
      the treatment-free periods, normal testosterone levels were obtained, resulting
      in a cessation of the symptoms of androgen suppression and an improvement in
      quality of life. CONCLUSIONS: These results indicate that IAD is an effective and
      feasible therapy in patients with early stages of prostate cancer. Larger trials
      are necessary to confirm these encouraging results. Therefore, a European
      prospective, randomized, multicenter study (RELAPSE study) has been started to
      compare IAD with continuous androgen blockade in terms of time to tumor
      progression, safety and quality of life in patients with PSA relapse after
      radical prostatectomy.

PMID- 10081701
TI  - Intermittent complete androgen blockade in metastatic prostate cancer.
AB  - INTRODUCTION: Intermittent hormonal treatment of prostate cancer was first
      developed based upon experimental study results. Using the Shionogi mouse breast
      cancer model, it was shown that the tumor grows rapidly in the presence of
      androgens, then undergoes apoptotic regression when androgens are removed. This
      apoptotic potential can be reinduced several times by cyclic replacement and
      withdrawal of androgens. These results led to the concept being evaluated in
      clinical trials. METHOD: In most of the clinical studies a protocol is used in
      which the patient receives 36 weeks of androgen deprivation. For those patients
      whose prostate-specific antigen (PSA) drops to less than 4 ng/ml within 32 weeks
      of therapy, the androgen withdrawal is stopped at 36 weeks, and not reintroduced
      until PSA increases to 20 ng/ml. This cycle is then repeated until the patient's
      tumor becomes hormone-sensitive. RESULTS: Akakura et al. in 1993, reported on 7
      patients who had a total of 12 episodes off-hormone therapy after achieving PSA
      complex remission, with further response after each re-exposure. Bruchovsky et
      al. in 1997, reported on 47 patients who entered a study of intermittent hormone
      therapy to evaluate the effect of cyclic withdrawal and replacement therapy in 14
      D2, 10 D, 19 C, 2 B2, 2 A2 patients. Treatment was initiated with combined
      androgen blockade and continued for at least 6 months until a serum PSA nadir was
      observed. The first two treatment cycles lasted 73 and 75 weeks, with a mean time
      off therapy of 30 and 33 weeks and an overall mean percentage time-off therapy of
      41 and 45%. Serum testosterone returned to the normal range within 8 weeks
      (range: 1-26 weeks) of stopping treatment. The off-treatment period in both
      cycles was associated with an improvement in sense of well-being, and the
      recovery of libido and potency in the men who reported normal or near-normal
      sexual function before the start of therapy. In 7 patients with stage D2 disease,
      the cancer progressed to an androgen-independent state. The mean and median times
      to progression were 128 and 108 weeks. Seven patients died, one from a non-cancer
      related illness, with mean and median overall survival times of 210 and 166
      weeks. CONCLUSION: These studies demonstrated that the androgen-dependent state
      of prostate cancer can be maintained during a course of intermittent androgen
      suppression, supporting the possibility of multiple apoptotic regressions under
      well-regulated conditions. Oliver et al. in 1997, conducted a retrospective study
      of 20 patients and concluded that intermittent androgen deprivation reduced
      induction of hormone-resistant prostate cancer, with no acute or major risk
      associated with the use of intermittent androgen suppression. More clinical
      studies are required to clarify the indication for intermittent hormone therapy
      and evaluate improvement in quality of life and survival. In the future,
      approaches to the improvement of therapeutic apoptosis could include intermittent
      hormone therapy, associated with additive cytotoxic therapeutic strategies.

PMID- 10081702
TI  - Spike generation from dorsal roots and cutaneous afferents by hypoxia or
      hypercapnia in the rat in vivo.
AB  - The present study aimed at investigating the responsiveness of different parts of
      the primary afferent neurones to a brief hypoxia, hypercapnia or ischaemia under
      in vivo conditions. Action potentials were recorded in separate groups of
      anaesthetized rats from (i) the peripheral end of the central stump of the cut
      L3, L4 or L5 dorsal root (dorsal root preparation); (ii) the central end of the
      peripheral stump of the cut saphenous nerve (saphenous-receptor preparation);
      (iii) the distal end of a segment of the saphenous nerve cut at both ends (axon
      preparation). In paralysed animals interruption of artificial ventilation for 20
      60 s elicited or increased the frequency of action potentials in both the dorsal
      root and saphenous-receptor preparations. Activation of these preparations was
      also achieved by inspiration of gas mixtures containing 10-0% oxygen (mixed with
      nitrogen) or 20-50% carbon dioxide (mixed with oxygen) which elicited in the
      blood a decrease in PO2 or an increase in PCO2 with a fall in pH. Occlusion of
      the femoral artery for 3 min also caused spike generation in the saphenous
      receptor preparations with little alteration in blood pressure. All these stimuli
      failed to evoke action potentials in the axon preparations. Systemic (300 mg kg-1
      s.c.) or perineural (2%) capsaicin pretreatment failed to inhibit the effect of
      hypoxia, hypercapnia or ischaemia, indicating a significant contribution of
      capsaicin-insensitive neurones to the responses. It is concluded that central and
      peripheral terminals but not axons of primary afferent neurones are excited by a
      brief hypoxia or hypercapnia and the peripheral terminals by a short local
      ischaemia as well. Excitation of central terminals by hypoxia or hypercapnia
      revealed in this way an antidromic activation of dorsal roots in response to
      natural chemical stimuli.

PMID- 10081703
TI  - Separate receptors mediate oxytocin and vasopressin stimulation of cAMP in rat
      inner medullary collecting duct cells.
AB  - The two neurohypophysial hormones arginine vasopressin (AVP) and oxytocin have
      actions in the inner medullary collecting duct (IMCD) where both peptides induce
      an increase in cAMP accumulation. The present study has employed a novel IMCD
      cell line to determine whether these two hormones induce cAMP accumulation via
      common or separate receptors, and to characterize the potential receptors
      responsible. Equal volumes of vehicle (150 mM NaCl) or hormone/antagonist
      solutions were added to aliquots of 10(4) IMCD cells in the presence of 10(-3) M
      3-isobutylmethylxanthine (IBMX) and incubated at 37 degrees C for 4 min. cAMP
      levels were determined by radioimmunoassay and protein concentration by Bradford
      assay. Both AVP and oxytocin elicited dose-dependent increases in cAMP
      generation, though oxytocin was less potent than AVP (EC50 = 1.6 x 10(-8) M vs.
      7.4 x 10(-10) M). AVP at 10(-8) M and oxytocin at 10(-8) M, concentrations
      sufficient to elicit near-maximal cAMP accumulation, resulted in cAMP levels of
      73.4 +/- 1.7 and 69.0 +/- 3.3 pmol (mg protein)-1 (4 min)-1, respectively (n =
      10), compared with the vehicle-treated basal value of 37.7 +/- 2.2 pmol (mg
      protein)-1 (4 min)-1 (P < 0.001, n = 10). Combined AVP (10(-8) M) and oxytocin
      10(-6) M) resulted in cAMP accumulation of 63.8 +/- 3.1 pmol (mg protein)-1 (4
      min)-1 (n = 10), which was not significantly different from the effect of
      oxytocin alone, but slightly less than that for AVP alone (P < 0.05). A
      submaximal concentration of AVP (10(-10) M) induced cAMP accumulation of 48.6 +/-
      2.5 pmol (mg protein)-1 (4 min)-1 (P < 0.01 compared with basal level of 34.9 +/-
      2.4 pmol (mg protein)-1 (4 min)-1, n = 10), which was blocked in the presence of
      a vasopressin V2 receptor antagonist (10(-7) M OPC-31260) but not by the oxytocin
      receptor antagonist (10(-6) M [Pen1,pMePhe2, Thr4,Orn8]oxytocin) (36.3 +/- 6.1
      and 45.1 +/- 1.3 pmol (mg protein)-1 (4 min)-1 respectively, P < 0.05, n = 10). A
      submaximal concentration of oxytocin (10(-7) M) induced a cAMP accumulation of
      45.8 +/- 1.8 pmol (mg protein)-1 (4 min)-1 (n = 10), which was reduced by
      addition of 10(-6) M oxytocin antagonist (36.3 +/- 2.1 pmol (mg protein)-1 (4
      min)-1, P < 0.05, n = 10), whereas co-incubation with 10(-6) M of the V2 receptor
      antagonist had no effect (43.2 +/- 1.3 pmol (mg protein)-1 (4 min)-1, n = 10).
      These results indicate that AVP and oxytocin induce cAMP accumulation from a
      common ATP pool in IMCD cells, and that separate vasopressin V2 and oxytocin
      receptor systems are involved, perhaps coupled to a common adenylate cyclase
      system.

PMID- 10081704
TI  - Anion efflux from cytotrophoblast cells derived from normal term human placenta
      is stimulated by hyposmotic challenge and extracellular A23187 but not by
      membrane-soluble cAMP.
AB  - The regulation of placental anion transport influences fetal accretion and
      placental homeostasis. We investigated whether efflux of 125I- or 36Cl- from
      multinucleated cytotrophoblast cells derived from human term placenta is
      regulated by one of three stimuli: (a) the calcium ionophore A23187, (b) a
      'cocktail' of agents designed to raise intracellular levels of cAMP, (c) a
      hyposmotic solution. After loading with the appropriate isotope for 2 h and
      thorough washing, cells were exposed to sequential aliquots of buffer applied and
      removed each minute. Following an equilibration period of 5 min one of the
      stimuli was applied at room temperature At the end of the experiment the cells
      were lysed to give a lysate count which was used to express the count obtained
      from each aliquot as percentage efflux of that possible for that minute. The cAMP
      'cocktail' and A23187 were applied for 5 min; the hyposmotic solution was applied
      for 10 min. The results for 125I- at 7 min showed that the mean efflux in the
      presence of hyposmotic shock was greater than control (5.7 +/- 1.0% min-1 versus
      2.2 +/- 0.1% min-1, respectively; mean +/- S.E.M., n = 4 placentas). Similarly
      mean efflux at 6 min in the presence of A23187 was also significantly greater
      than control (6.5 +/- 1.9% min-1 versus 2.6 +/- 1.0% min-1, respectively, n = 3
      placentas). The mean efflux in the presence of the cAMP cocktail was not
      different from control at any time point. The results were qualitatively the same
      if 36Cl- was used in the place of 125I- and when the experiment was performed
      with 36Cl- in a HCO3- buffer gassed with CO2. Mean 125I- efflux at 6 min in
      response to hyposmotic challenge was 33% less (P < 0.01) in the presence of 1 mM
      4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 37% less (P <
      0.005) in the presence of 10 microM tamoxifen but no different if the hyposmotic
      solution was nominally calcium free. We conclude that there are differential
      effects of second messengers on anion efflux from the differentiated
      cytotrophoblast cells.

PMID- 10081705
TI  - Ryanodine receptors in human bladder smooth muscle.
AB  - The role of intracellular Ca2+ release in the activation of human bladder smooth
      muscle is controversial. We have measured the expression of mRNA encoding for the
      ryanodine receptor (RyR) isoforms (RyR1, RyR2 and RyR3) in isolated human
      detrusor smooth muscle. mRNA for RyR2 was detected in all samples but no mRNA for
      RyR1 or RyR3 could be found. Human bladder smooth muscle cells in culture are
      unresponsive to caffeine, suggesting the absence of a functional RyR system.
      However, mRNA encoding for RyR2 was detected in these cells. Using saponin
      permeabilized cells, a Ruthenium Red-sensitive Ca(2+)-dependent 45Ca2+ release
      could be demonstrated from the sarcoplasmic reticulum (SR). These data confirm
      the functional presence of Ca(2+)-induced Ca2+ release (CICR) in cells and
      suggest that the properties of the RyR2 isoform in human detrusor may change when
      the cells are maintained in culture. The implications of these observations to
      detrusor smooth muscle function are discussed.

PMID- 10081706
TI  - Hypoxia inhibits baroreflex vagal bradycardia via a central action in
      anaesthetized rats.
AB  - It is known that arterial baroreflexes are suppressed in stressful conditions.
      The present study was designed to determine whether and how hypoxia affects
      arterial baroreflexes, especially the heart rate component, baroreflex vagal
      bradycardia. In chloralose-urethane-anaesthetized rats, baroreflex vagal
      bradycardia was evoked by electrical stimulation of the aortic depressor nerve,
      and the effect of 15 s inhalation of hypoxic gas (4% O2) was studied. Inhalation
      of hypoxic gas was found to inhibit baroreflex vagal bradycardia. The inhibition
      persisted after bilateral transection of the carotid sinus nerve. Cervical vagus
      nerves were cut bilaterally and their peripheral cut ends were stimulated to
      provoke vagal bradycardia of peripheral origin so as to determine whether hypoxia
      could inhibit vagal bradycardia by acting on a peripheral site. In contrast to
      baroreflex vagal bradycardia, the vagus-induced bradycardia was not affected by
      hypoxic gas inhalation. It is concluded that baroreflex vagal bradycardia is
      inhibited by hypoxia and the inhibition is largely mediated by its direct central
      action.

PMID- 10081707
TI  - The effects of acute and chronic systemic hypoxia on muscle oxygen supply and
      oxygen consumption in the rat.
AB  - The aims of the present study were to evaluate how acute systemic hypoxia affects
      O2 delivery to skeletal muscle and muscle O2 consumption (VO2) of the rat and to
      establish how these relationships are altered by chronic systemic hypoxia. Thus,
      the effects of breathing different concentrations of O2 (air, 12% and 8% O2) upon
      oxygen delivery and VO2 were studied in hindlimb muscles of control, normoxic (N)
      rats and of rats that had been made chronically hypoxic in a chamber at 12% O2
      for 3-4 weeks (CH) rats. Under anaesthesia, arterial blood pressure, femoral
      blood flow (FBF), arterial O2 content (Ca,O2) and venous O2 content in the efflux
      from hindlimb were measured. In N rats, changing the inspirate from air to 12%
      and 8% O2 for 5 min each, reduced Ca,O2 from 20 +/- 0.3 ml (100 ml)-1 in air to
      13 +/- 1.0 ml (100 ml)-1 in 8% O2. FBF did not change significantly (1.7 +/- 0.1
      ml min-1 in air) so that O2 delivery to hindlimb muscles fell from 0.28 +/- 0.07
      to 0.16 +/- 0.02 ml min-1 in 8% O2. Nevertheless, the VO2 of hindlimb muscle was
      well maintained: 0.06 +/- 0.02 ml min-1 in air and 0.08 +/- 0.02 ml min-1 in 8%
      O2. In CH rats breathing 12% O2, Ca,O2 (23 +/- 1.0 ml (100 ml)-1) was comparable
      to that of N rats breathing air, due to an increase in haematocrit, as were FBF
      (1.6 +/- 0.2 ml min-1) and O2 delivery (0.39 +/- 0.05 ml min-1). However, VO2 was
      2.5-fold greater in CH rats (0.16 +/- 0.03 ml min-1). As in N rats, FBF was well
      maintained at 1.7 +/- 0.2 and 1.6 +/- 0.2 ml min-1 in 8% O2 and air,
      respectively. Further, VO2 was also well maintained, at 0.17 +/- 0.02 and 0.12 +/
      0.02 ml min-1 in 8% O2 and air, respectively. These results suggest that,
      contrary to previous reports, muscle VO2 of the rat is independent of O2 delivery
      over a wide range of O2 delivery values. They also suggest that muscle VO2 of CH
      rats is similarly independent of O2 delivery. The novel finding that muscle VO2
      has a greater absolute value in CH rats can, we propose, be explained by an
      increase in VO2 of the vasculature rather than of the skeletal muscle fibres and
      reflects increased biosynthetic activity of the vessel walls and/or vascular
      remodelling.

PMID- 10081708
TI  - Cardiac function and morphology studied by two-dimensional Doppler
      echocardiography in unsedated newborn pigs.
AB  - The newborn pig is currently the most used species in animal neonatal research.
      Valid non-invasive monitoring is important in particular for long-term survival
      of unsedated animals. In the unsedated newborn pig (n = 35, median age 24 h,
      range 7-48 h) we standardized two-dimensional Doppler echocardiography and
      determined the normal ranges for cardiac function. Probe positioning had to be
      adjusted to the V-shaped thorax and the mid-line position of the heart. Six out
      of the sixteen animals < 20 h had a patent ductus arteriosus compared with one of
      the twenty animals > 20 h old. One atrial septal defect (5 mm) and one small
      ventricular septal defect were diagnosed. The average heart size was 0.7-0.9% of
      body weight which is similar to human infants of the same size. The mean aortic
      diameter was 6.0 +/- 0.5 mm (mean +/- S.D.) and cardiac output was 0.38 +/- 0.08
      l min-1; both correlate with body weight (r = 0.80 and 0.73, respectively).
      Tricuspid regurgitation velocity was 3.0 +/- 0.4 m s-1 (mean +/- S.D.), giving an
      estimated pressure gradient across the tricuspid valve of 37 +/- 9.7 mmHg. The
      aortic diameter and the heart weight per kg body weight are comparable to those
      reported for preterm neonates. The cardiac output and velocities across the four
      valves are more comparable with term neonates.

PMID- 10081709
TI  - Exercise gas transport determinants in elderly normotensive and hypertensive
      humans.
AB  - This study examined the effect of the phenylalkylamine calcium channel blocker
      verapamil, on resting left ventricular (LV) function and O2 uptake rate (VO2)
      during exercise at maximal and submaximal work rates. Nine older hypertensive (71
      years; OH), 10 older sedentary normotensive (69 years; OS), 10 older active (71
      years; OA) and 10 young (24 years; Y) individuals volunteered. Studies were
      completed in the control condition and 4-6 h following 240 mg verapamil SR per
      os. Resting LV systolic (fractional shortening; FS) and diastolic (early: late
      (E/A) flow velocity ratio and isovolumic relaxation time (IVRT) were measured by
      Doppler echocardiography. Maximal oxygen uptake (VO2,max) and, on subsequent test
      days, four transitions to and from a 6 min square wave exercise perturbation at a
      sub-anaerobic threshold intensity of 40 W (OH, OS, OA) or 100 W (Y) for
      determination of VO2 kinetics were performed on a cycle ergometer. Breath-by
      breath VO2 transients were fitted with a monoexponential equation, starting at
      phase 2 of the response, while heart rate (HR) was fitted from phase 1, for the
      determination of the time constant of VO2 (tau VO2) and HR (tau HR). Baseline
      left ventricular FS was significantly greater in the OS (32%), OA (34%) and Y
      (34%) than in the OH (23%) groups, while E/A was significantly greater in the OA
      (1.16) and Y (2.34) than in the OH (0.9) and OS (0.82) groups (P < 0.05).
      Baseline VO2,max was higher and tau VO2 faster in the young (41.4 ml kg-1 min-1;
      25.2 s) than in the older groups and in the OA (28.8 ml kg-1 min-1; 44.3 s) than
      in both OH (20.8 ml kg-1 min-1; 71.3 s) and OS (22.0 ml kg-1 min-1; 59.5 s)
      groups (P < 0.05). Heart rate kinetics showed similar differences to VO2 kinetics
      among the groups. After verapamil, no significant changes in FS, E/A or IVRT were
      observed in the OA and Y groups. In the OH group, FS (32%) and E/A (1.15)
      increased while IVRT decreased significantly (from 0.103 to 0.07; P < 0.05). In
      the OS group, only E/A increased significantly (0.82 to 1.0; P < 0.05). None of
      the exercise variables (VO2,max, tau VO2 or tau HR) were altered for the OA or Y
      groups. VO2,max increased (from 20.8 to 22.8 ml kg-1 min-1) in the OH and (from
      22.0 to 24.1 ml kg-1 min-1) in the OS (P < 0.05). tau VO2 was accelerated from
      71.3 to 49.2 s in the OH group and from 59.5 to 48.2 s in the OS group (P <
      0.05). These results suggest that VO2 responses at maximal and submaximal work
      rates may be dependent upon the initial cardiac pump function of the study
      population.

PMID- 10081710
TI  - Evolution of contractile and elastic properties of rat soleus muscle fibres under
      unloading conditions.
AB  - Rats were submitted to 14 days of hindlimb suspension in order to examine the
      contractile and elastic properties of the soleus muscles under disuse conditions.
      The calcium/strontium activation properties, the maximal shortening velocity
      (V0), as well as the time behaviour of force transients following quick releases
      and the T1 curves characterizing the active part of the series elastic elements,
      were determined on single chemically skinned fibres. After the functional
      measurements, the fibres were subjected to sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis in order to analyse both the myosin heavy (MHC) and light
      (MLC) chain isoforms. According to the MHC and MLC composition, two groups of
      fibres were defined after hindlimb suspension: a group of slow fibres expressing
      the slow set of both MHC and MLC isoforms, and a group of fast fibres co
      expressing the slow and fast MHC and MLC isoforms with a predominant expression
      of the fast ones. For the first group, the contractile as well as the elastic
      properties were found to be close to those of control slow soleus fibres. For the
      second group, both contractile and elastic properties were modified insofar as
      they became close to those found in a fast muscle such as the extensor digitorum
      longus. We suggested that between the two populations found in the soleus muscle
      after hindlimb suspension the modifications in the contractile properties, as
      well as the alterations in the elastic characteristics, were concomitant to the
      changes in both MHC and MLC compositions.

PMID- 10081711
TI  - Breathing patterns during slow and fast ramp exercise in man.
AB  - Breathing frequency (fb), tidal volume (VT), and respiratory timing during slow
      (SR, 8 W min-1) and fast (FR, 65 W min-1) ramp exercise to exhaustion on a cycle
      ergometer was examined in seven healthy male subjects. Expiratory ventilation
      (VE), pulmonary gas exchange (VO2 and VCO2) and end-tidal gas tensions (PET,O2
      and PET,CO2) were determined using breath-by-breath techniques. Arterialized
      venous blood was sampled from a dorsal hand vein at 2 min intervals during SR and
      30 s intervals during FR and analysed for arterial plasma PCO2 (PaCO2). PET,CO2
      increased with increasing work rates (WRs) below the ventilatory threshold (VT);
      at WRs > or = 90% VO2,max, PET,CO2 was reduced (P < 0.05) below 0 W values in SR
      but not in FR.fb and VT were similar for SR and FR at all submaximal WRs,
      resulting in a similar VE. At exhaustion VE was similar but fb was higher (P <
      0.05) and VT was lower (P < 0.05) in SR (fb, 51 +/- 10 breaths min-1; VT, 2590 +/
      590 ml) than in FR (fb, 42 +/- 8 breaths min-1; VT, 3050 +/- 470 ml). The time
      of expiration (TE) decreased with increasing WR, but there was no difference
      between SR and FR. The time of inspiration (TI) decreased at exercise intensities
      > or = VT; at exhaustion, TI was shorter (P < 0.05) during SR (0.512 +/- 0.097 s)
      than during FR (0.753 +/- 0.100 s). The TI to total breath duration (TI/TTot) and
      the inspiratory flow (VT/TI) were similar during SR and FR at all submaximal
      exercise intensities; at VO2,max, TI/TTot was lower (P < 0.05) and VT/TI was
      higher (P < 0.05) during SR (TI/TTot, 0.473 +/- 0.030; VT/TI, 5.092 +/- 0.377 l s
      1) than during FR (TI/TTot, 0.567 +/- 0.050; VT/TI, 4.117 +/- 0.635 l s-1). These
      results suggest that during progressive exercise, breathing pattern and
      respiratory timing may be determined, at least at submaximal work rates,
      independently of alveolar and arterial PCO2.

PMID- 10081712
TI  - Effects of moderate exercise training on plasma volume, baroreceptor sensitivity
      and orthostatic tolerance in healthy subjects.
AB  - The effect of physical training on an individual's ability to withstand an
      orthostatic stress is unclear. This study was undertaken to determine the effects
      on orthostatic tolerance in healthy volunteers of training at a level appropriate
      for unfit subjects and cardiorespiratory patients. In 11 asymptomatic, untrained
      subjects the following assessments were made: plasma volume by Evans Blue dye
      dilution and blood volume derived from haematocrit; carotid baroreceptor
      sensitivity from the slope of the regression of change in cardiac interval
      against pressure applied to a neck chamber; orthostatic tolerance as time to
      presyncope in a test of head-up tilting combined with lower body suction;
      exercise test relating heart rate to oxygen consumption. Subjects were then given
      a training schedule (5BX/XBX, Royal Canadian Air Force) involving 11-12 min of
      mixed exercises per day until an age/sex related 'target' was reached. Following
      training all subjects showed evidence of improved fitness, seen as decreases in
      heart rate at an oxygen uptake (Vo2) of 1.5 1 min-1 and in the elevation of the
      regression line between heart rate and Vo2. All also had increases in plasma and
      blood volumes and decreases in baroreceptor sensitivity. Seven of the subjects
      showed increases in orthostatic tolerance. Improvement in orthostatic tolerance
      was related to a low initial tolerance, and was associated with increases in
      plasma volume and decreases in baroreceptor sensitivity. These results show that
      moderate exercise training increases orthostatic tolerance in subjects who do not
      already have a high initial tolerance and suggest that training may be of value
      in the management of untrained patients with attacks of syncope due to
      orthostatic intolerance.

PMID- 10081713
TI  - The activation of bladder wall afferent nerves.

PMID- 10081714
TI  - The spontaneously hypertensive rat: insight into the pathogenesis of irritative
      symptoms in benign prostatic hyperplasia and young anxious males.
AB  - Recent epidemiological studies have shown that hypertensive men are more likely
      to undergo surgical intervention for irritative voiding symptoms from BPH than
      age-matched controls. Indeed, noradrenergic nerves which regulate vascular tone
      also participate in the functional component of bladder outlet obstruction due to
      BPH. Newer, less invasive therapies for BPH such as thermal therapy can relieve
      symptoms yet do not eliminate obstruction based on urodynamic studies.
      Coincidentally, drugs such as alpha-adrenoceptor antagonists, which have been
      thought to relieve obstruction due to a peripheral effect, can be given
      intrathecally in animals to relieve urinary frequency due to obstruction. Taken
      together these observations implicate both peripheral and central sympathetic
      pathways in the motor control of the urinary bladder especially with disease
      states. We have used the hypertensive and behaviourally hyperactive spontaneously
      hypertensive rat (SHR), to investigate the roles sympathetic pathways or
      micturition. Elevated nerve growth factor (NGF) derived from vascular and bladder
      smooth muscle cells of the SHR appears to direct morphological, biochemical, and
      functional changes. The increase in NGF can apparently be explained by
      stabilization of its mRNA leading to increased synthesis in NGF. Bladders from
      SHRs develop a profuse noradrenergic hyperinnervation compared with the control
      WKY strain. Since afferents supplying the SHR bladder are hypertrophied, changes
      in afferent pathways are also likely. These differences in innervation and NGF in
      the SHR may explain changes in function. SHRs void 3 times as frequently as their
      genetic controls. Urinary frequency can be reduced by alpha-adrenoceptor
      antagonists. Cystometrograms performed in SHRs reveal lower bladder capacities
      and micturition volumes and the presence of unstable contractions compared with
      the WKY rat. Intrathecal, rather than intra-arterial administration of the alpha
      adrenoceptor antagonist doxazosin reduces unstable contractions in the SHR. In
      vitro muscle bath studies have shown enhanced responses of SHR bladder smooth
      muscle to alpha-adrenoceptor agonists. It is likely that upregulation of NGF
      production causes sensory and possibly noradrenergic pathways to elicit
      hyperactive voiding. Increase in NGF in the adult bladder due to pathological
      conditions yields similar, yet distinct, consequences for voiding behaviour and
      innervation. Likewise, increased NGF in adult bladders following obstruction or
      inflammation triggers neuronal hypertrophy, enhanced reflex activity and urinary
      frequency. In contrast to the SHR, hyper-innervation is not observed. Moreover,
      peripheral or spinal alpha-adrenoceptor blockade eliminates urinary frequency
      following obstruction. These observations support the role for sympathetic
      pathways in the motor function of the bladder, especially in congenital or adult
      disease states. A similar process may underlie the neuroplasticity involved in
      alterations after obstruction or inflammation of the lower urinary tract in
      humans. The SHR strain raises the possibility that a common genetic defect exists
      capable of predisposing to both hypertension and overactivity of the urinary
      bladder. Whether a genetic predisposition to sustained bladder overactivity in
      response to inflammatory stimuli in obstruction exists in humans is an intriguing
      prospect.

PMID- 10081715
TI  - Neuromodulation of the lower urinary tract.

PMID- 10081716
TI  - Bladder instability and detrusor smooth muscle function.

PMID- 10081717
TI  - Metabolic factors influencing lower urinary tract function.

PMID- 10081718
TI  - Advances in the pharmacological control of the bladder.
AB  - To effectively control bladder activity, and to treat urinary incontinence caused
      by bladder overactivity, identification of suitable targets for pharmacological
      intervention is necessary. Such targets may be found in the central nervous
      system (CNS) or peripherally. The causes of bladder overactivity are not known,
      but theoretically increased afferent activity, decreased inhibitory control in
      the CNS and/or peripheral ganglia, and increased sensitivity of the detrusor to
      efferent stimulation may be involved. Several CNS transmitters may modulate
      voiding, but few drugs with a defined CNS site of action have been developed for
      treatment of voiding disorders. Potentially, drugs affecting GABA, opioid, 5-HT,
      noradrenaline, dopamine, or glutamatergic receptors and mechanisms can be
      developed, but a selective action on the lower urinary tract may be difficult to
      obtain. Traditionally, drugs used for treatment of bladder overactivity have had
      a peripheral site of action, mainly the efferent neurotransmission or the
      detrusor muscle itself. Antimuscarinic drugs, beta-adrenoceptor agonists, alpha
      adrenoceptor antagonists, drugs affecting membrane channels, prostaglandin
      synthetase inhibitors and several other agents have been used. However, none of
      them has been developed specifically for treatment of bladder disorders, and
      their efficacy, as judged from controlled clinical trials (where performed), is
      often limited. Recent information on the alpha-adrenoceptor, beta-adrenoceptor
      (beta 3), and muscarinic receptor subtypes of the human detrusor and outflow
      region can be the basis for the development of compounds with effect on bladder
      overactivity and with improved tolerance. New ways of decreasing acetylcholine
      release may represent a promising way of controlling bladder contraction.
      Potassium channel (KATP) openers are theoretically attractive, but the drugs
      available so far have targeted vascular rather than bladder smooth muscle, which
      has limited their clinical use. However, new drugs belonging to these groups with
      an interesting profile of action have been developed. Drugs decreasing afferent
      activity represent an attractive therapeutic approach and transmitters of
      afferent nerves and their receptors are possible targets for pharmacological
      interventions. Tachykinins, such as substance P, neurokinins A and B, and other
      neuropeptides have been demonstrated in nerves of the lower urinary tract and
      have been shown to influence bladder function. Agents affecting these nerves by
      causing release of tachykinins, such as capsaicin and resiniferatoxin, given
      intravesically can be effective in some cases of bladder overactivity, and agents
      antagonizing tachykinin receptors may also be of therapeutic interest. New drugs
      specifically directed for control of bladder activity are under development and
      will hopefully lead to improved treatment of urinary incontinence.

PMID- 10081719
TI  - The physiology of the mammalian urinary outflow tract.
AB  - Urinary outflow from the mammalian bladder occurs through the urethra. This
      outflow tract is a complicated structure composed of striated and smooth muscle
      and vascular urothelium. It is controlled by somatic and autonomic nerves and has
      several functions: it generates sustained tone to prevent urinary leakage during
      bladder filling; it generates transient reflex increases in pressure to prevent
      opening of the lumen when abdominal pressure rises; it undergoes relaxation
      preceding micturition and can generate urethral opening and shortening during
      micturition. A urethral pressure profile shows a peak pressure of > or = 100
      cmH2O. The outermost coat is striated muscle, the striated or external sphincter.
      The fibres are predominantly circularly oriented. The extent varies in different
      species and between sexes. In the human female it extends the length of the
      urethra, and is composed mainly of slow twitch fibres. In the male, the sphincter
      extends from the membranous urethra over the base of the prostate and has nearly
      equal numbers of slow and fast twitch fibres. In both sexes, the posterior border
      may be deficient in striated muscle, and filled by circularly oriented smooth
      muscle. Activity in the slow twitch fibres through somatic nerves may be
      continuous during bladder filling. Outer circular and inner longitudinal smooth
      muscle is present Strips from either layer will generate sustained tone
      particularly if dissected from the high pressure zone. This tone is myogenic, and
      may be achieved in the absence of action potentials, but relies on influx of
      calcium through L-type calcium channels. Both layers receive sympathetic and
      parasympathetic excitatory innervation and nitrergic inhibitory innervation.
      Normal urethral pressure requires blood flow to the urothelium (lamina propria).
      Striated and smooth muscles are both thought to contribute to the resting
      urethral pressure in the human. The precise role of the smooth muscles during
      micturition is as yet unresolved.

PMID- 10081720
TI  - Volumetric change of the lateral ventricles in the human brain following glucose
      loading.
AB  - Lateral ventricular volumes were monitored and quantified using accurately
      registered magnetic resonance images (MRIs) in six healthy individuals 30 min
      before and up to 4 h after ingestion of a glucose drink. The volume of the
      lateral ventricles increased by an average (+/- S.E.M.) of 2.4 +/- 0.4% as blood
      glucose levels rose from 4.8 +/- 0.2 mmol l-1 to 8.4 +/- 0.4 mmol l-1. This was
      followed by a peak decrease of 5.99 +/- 3.3% below initial fasting volumes as
      blood glucose levels fell to 5.0 +/- 0.3 mmol l-1. We suggest that the secondary
      volume decrease demonstrates a homeostatic process of brain volume regulation for
      which the mechanism remains uncertain.

PMID- 10081721
TI  - Corneal surface disease topology.
AB  - The specific morphology and distribution of corneal surface lesions may point
      toward a specific diagnosis and pathogenesis in individual cases (see Fig 1).
      Staining lesions may be fine (e.g., staphylococcal) or punctate (e.g., keratitis
      sicca). The size and appearance of staining and nonstaining lesions of the
      epithelium and subepithelial cornea may be characteristic for a particular
      disease process (e.g., HSV, EKC). Finally, the location of lesions is important.
      Inferior staining (staphylococcal disease, lagophthalmos) will be incited by a
      different cause as compared to superior (molluscum, trachoma, vernal
      keratoconjunctivitis) and peripheral (contact lens-induced, collagen vascular
      disease) staining patterns. Central lesions are more likely to indicate tear
      deficiency, superficial corneal dystrophies, viral infections, or metabolic
      conditions. Knowledge of these patterns of disease can allow accurate diagnosis
      and more expedient and successful treatment of corneal surface disease.

PMID- 10081722
TI  - Toxic keratopathy.

PMID- 10081723
TI  - The dry eye: a diagnostic dilemma.

PMID- 10081724
TI  - Corneal findings in ocular allergy.

PMID- 10081725
TI  - Rheumatoid diseases.

PMID- 10081726
TI  - Mooren's ulcer.

PMID- 10081727
TI  - Topical issues in the treatment of bacterial keratitis.

PMID- 10081728
TI  - Fungal keratitis.

PMID- 10081729
TI  - Ocular chlamydial infections.

PMID- 10081730
TI  - Herpes simplex anterior uveitis.

PMID- 10081731
TI  - Varicella zoster virus ocular disease.
AB  - Our understanding of the spectrum of diseases caused by VZV continues to evolve
      with new and atypical presentations. Newer diagnostic studies are implicating VZV
      as the cause of a host of inflammatory conditions, some of which present sine
      herpete. Finally, the continued development of antiviral drugs and vaccines will
      allow safer and more effective treatment of VZV and its complications.

PMID- 10081732
TI  - Corneal, anterior segment, and adnexal manifestations of human immunodeficiency
      virus.

PMID- 10081733
TI  - Parasitic corneal infections.

PMID- 10081734
TI  - Interstitial keratitis.

PMID- 10081735
TI  - Surgical management of infectious and noninfectious keratitis.

PMID- 10081736
TI  - Ginkgo biloba for antidepressant-induced sexual dysfunction?

PMID- 10081737
TI  - Caution recommended.

PMID- 10081738
TI  - Gender identity disorder in the DSM-IV.

PMID- 10081739
TI  - Dynamics of self-acceptance and mate acceptance in sexual life.

PMID- 10081741
TI  - Improving practice in marriage preparation.
AB  - Developments over the past 2 decades concerning research on marriage preparation
      programs are reviewed. Suggestions for designing effective programs are
      presented. Issues reviewed include assessing client needs, the timing and
      duration of programs, formats and methods, program content, provider
      characteristics, and promotion and marketing strategies.

PMID- 10081740
TI  - Sexual response in women with spinal cord injuries: implications for our
      understanding of the able bodied.
AB  - This study assesses the impact of psychogenic and reflex sexual arousal on women
      with complete and incomplete spinal cord injuries (SCIs) and explores the effects
      of SCI on orgasm in women. Thirty women with SCIs and 10 able-bodied women
      participated in the study. Three individual experiments were conducted over a 3
      day period, assessing (a) the impact of SCI on psychogenic sexual arousal, (b)
      the impact of SCI on orgasm; and (c) the impact of SCI on reflex sexual arousal.
      Results support the hypothesis that women with complete SCIs and upper motor
      neuron injuries affecting the sacral spinal segments and women with incomplete
      upper motor neuron SCIs had the capacity for reflex lubrication. Women with SCIs
      were significantly less likely than able-bodied women to achieve orgasm. However,
      there was not a significant difference among women with different SCIs to achieve
      orgasm.

PMID- 10081742
TI  - Does childhood sexual abuse cause borderline personality disorder?
AB  - Several studies have found that women with borderline personality disorder are
      more likely than controls to report a history of childhood sexual abuse.
      Researchers have generally assumed that childhood sexual abuse causes borderline
      personality disorder, but there are other possible interpretations of the
      association. We surveyed psychologists about the likelihood that patients with
      various personality disorders would engage in behaviors relevant to several
      alternative interpretations. Relative to patients with other personality
      disorders and to the "typical outpatient," patients with borderline personality
      disorder were rated as especially likely to misinterpret or misremember social
      interactions, to lie manipulatively and convincingly, and to have voluntarily
      entered destructive sexual relationships, possibly even at young ages. We discuss
      the plausibility of relevant alternative interpretations of the association
      between childhood sexual abuse and borderline personality disorder.

PMID- 10081743
TI  - The Golombok Rust Inventory of Sexual Satisfaction (GRISS): psychometric
      properties within a Dutch population.
AB  - The aim of this study was to investigate the psychometric properties of the
      Golombok Rust Inventory of Sexual Satisfaction (GRISS) in a Dutch population. The
      participants in this study were 373 heterosexual couples: 305 couples with a
      sexual problem and 68 student couples (test-retest). Evidence for a 12-factor
      solution corresponding to the original 12 subscales of GRISS was found, although
      some of the subscales were rather highly correlated. The homogeneity of the 12
      GRISS subscales, as determined by mean interitem correlations, item-rest
      correlations, and Cronbach's coefficient alpha, was satisfactory to good. The
      test-retest reliability of the GRISS scales was sufficient. The GRISS subscales
      were reasonably stable with respect to age, duration of the relationship, and
      level of education. Furthermore, a higher order factor analysis on the 12
      subscales suggested a male and a female sexual dissatisfaction factor.

PMID- 10081744
TI  - Life-long absence of sexual drive in a woman associated with 5
      dihydrotestosterone deficiency.
AB  - A case of a woman who presented with life-long absence of sexual drive is
      reported. Although her history contained psychological factors that might have
      been etiologic in her presentation, she had not responded to sex therapy or
      cognitive-behavior psychotherapy undertaken at other clinics. When seen by the
      author, she was found to have poorly developed external genitalia. The only
      abnormality discovered on endocrinological evaluation was a reduced level of 5
      dihydrotestosterone. Treatment with dihydrotestosterone gel applied to her vulva
      generated sexual drive and her ability to become sexually aroused.

PMID- 10081745
TI  - Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with
      dermal dysplasia.
AB  - The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow
      with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1),
      probably based on increasing turnover of the dermal collagen as reported
      previously, were morphologically and physico-chemically investigated. Cow 1 had
      about one and a half times as much as the body weight of normal Holstein cows,
      aged 5 to 6.5 years with stabilized growth. The bone samples were compared with
      those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported
      that the long-bone diaphysis of young calves and some herbivorous dinosaurs are
      occupied with laminar bone showing a concentric appositional formation, and that
      such a laminar bone is characteristically seen during the growing period of some
      farm animals and large dogs that show very rapid growth rates. Cow 1 had a
      smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis,
      and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the
      entire layers, although their bone volumes were similar among them. There were no
      significant differences in Ca and P concentrations and the Vickers microhardness
      values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of
      Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be
      some relation in collagen formation between the bone matrix of Cow 1 and the
      dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had
      probably shown growth until quite recently, so that we consider that Cow 1 became
      a giant animal, in the same way as some herbivorous dinosaurs.

PMID- 10081746
TI  - Oligodendroglial vacuolar degeneration in the bilateral motor cortices and
      astrocytosis in epileptic beagle dogs.
AB  - We performed a pathologic examination of the brains of three dogs in an epileptic
      beagle colony. Histologically, all the cases had diffuse astrocytosis in the
      cerebral cortex and basal ganglia as well as the hippocampus, whereas they showed
      acute nerve cell change in the hippocampus and some other areas of the cerebrum.
      One of these animals showed laminar myelin pallor associated with the presence of
      many vacuoles in the IV to VI layers of the bilateral motor cortices. Most of the
      vacuoles contained fine granules stained with luxol-fast-blue stain.
      Ultrastructural examination revealed that some oligodendrocytes and perineuronal
      satellite oligodendrocytes in the bilateral cerebral motor cortices of the two
      affected dogs had many vacuoles surrounded by myelin-like lamellar structures.
      These findings suggest a possibility that astrocytosis in the cerebrum and
      vacuolar degeneration of oligodendrocytes in the cerebral motor cortex may be, at
      least in part, related to the occurrence or development of seizures.

PMID- 10081747
TI  - A serosurvey of Borna disease virus infection in wild rats by a capture ELISA.
AB  - For a serological diagnostic test for Borna disease (BD), we developed a capture
      ELISA with specificity and sensitivity based on detection of antibodies against
      BD virus (BDV) p40 protein. Using our capture ELISA system, the antibody response
      of rats inoculated intracerebrally with BDV at 4 weeks after birth showed a sharp
      increase from 1 to 4 weeks postinoculation (p.i.) and a steady level after 5
      weeks p.i. To investigate prevalence of BDV infection among wild rats, we
      examined sera of Rattus norvegicus in Kami-iso town, Oshima district, Hokkaido,
      suggesting that rats in this area had not been infected by BDV.

PMID- 10081748
TI  - Detection of haptoglobin in the high-density lipoprotein and the very high
      density lipoprotein fractions from sera of calves with experimental pneumonia and
      cows with naturally occurring fatty liver.
AB  - In addition to the lipoprotein-deficient d > 1.25 fraction, haptoglobin was
      detected in the high-density lipoprotein (HDL) and the very high-density
      lipoprotein (VHDL) fractions from sera of calves with experimental pneumonia and
      cows with naturally occurring fatty liver. It was not found in the chylomicrons,
      very low-density lipoprotein and low-density lipoprotein fractions. Washing of
      the HDL fraction did not decrease the haptoglobin concentration. Transferrin and
      immunoglobulin G were immunoblotted to examine the possibility of contamination
      of the lipoprotein fractions by the d > 1.25 fraction. The two serum proteins
      were detected only in the d > 1.25 fraction, not in any lipoprotein fractions.
      The distribution pattern of haptoglobin in the lipoprotein fractions was distinct
      from that of serum albumin. Concentrations of haptoglobin in the HDL fractions
      from pneumonic sera were largely proportional to those in whole sera. Cholesteryl
      ester concentrations were decreased in sera from calves with pneumonia, as in
      cows with fatty liver. A protein immunologically related to hemoglobin was also
      detected in particular in the VHDL fractions from sera of both groups. These
      results suggest that haptoglobin or a complex with the hemoglobin-like protein
      may have a role or roles related to the lipid metabolism.

PMID- 10081749
TI  - Novel techniques for in vivo hemolysis studies in guinea pigs.
AB  - The in vivo toxic-hemolytic studies using small experimental animals are
      complicated by difficulties in preventing hemolysis during repeated collection of
      blood specimens and in measuring hemoglobin concentration in small amounts of
      plasma sample. To solve these problems we tried to develope the new techniques
      for the in vivo hemolysis studies using guinea pigs. The hemolysis accident was
      minimized to 2.75 mg/dl by collecting the blood directly into heparinized
      microhematocrit tubes by small longitudinal incision in the auricular artery. The
      hemoglobin in a small amount of sample (10 microliters) was determined by the new
      analytical system using a microflow spectrophotometer with a modified
      cyanmethemoglobin method. The standard curve of the hemoglobin concentration in
      the system revealed a line of Y = 1.8X + 0.79 (r = 0.999), CV < 1% with a minimum
      detectable concentration of 1.25 mg/dl. By using the new techniques, it was found
      that the plasma hemoglobin concentration in normal animals were 7.27 +/- 0.44
      mg/dl (mean +/- S.E.). The in vivo hemolytic activity of saponin was observed
      dose-dependently at doses of 30-50 mg/kg, i.v. in the guinea pigs. It is
      concluded that the present techniques are useful for in vivo hemolytic studies in
      small experimental animals such as guinea pigs.

PMID- 10081750
TI  - The hemolytic activity of bracken extracts in guinea pigs.
AB  - This study was conducted to elucidate the hemolytic activity of a new toxic
      substance in bracken fern. A crude extract (CE) was prepared from the methanol
      extracts of bracken by the column chromatography. When the CE was injected
      subcutaneously in guinea pigs, the hemoglobinuria and hemolysis were observed
      within 6 hr, and 3 days later edema and hemorrhages in the urinary bladder were
      observed. The CE was then fractionated by high performance liquid chromatography
      (HPLC), and three (HF, BF and CF) of the fractions showed the toxic activities in
      guinea pigs. The HF caused the hemolysis, whereas both the BF and the CF caused
      the hemorrhagic cystitis without any hemolytic activities. The HF was further
      fractionated by the HPLC, resulting of the 3 fractions (HF-I, II and III). The
      hemolysis was caused only with the HF-II, and HF-II as well as HF did not cause
      the hemorrhagic cystitis. HPLC analysis revealed that both BF and CF contains
      braxin B and braxin C, respectively, and both HF and HF-II do not contain braxin
      A, B or C. These facts suggest that bracken fern contains a new toxic substance
      (hemolysin) which induces the acute hemolysis in guinea pigs.

PMID- 10081751
TI  - A signaling pathway for stimulation of Na+ uptake induced by angiotensin II in
      primary cultured rabbit renal proximal tubule cells.
AB  - The aim of the present study was to examine the signaling pathways for a low dose
      of angiotensin II (ANG II) on Na+ uptake of primary cultured rabbit renal
      proximal tubule cells (PTCs) in hormonally defined serum-free medium. The results
      were as follows; ANG II (10(-11) M) stimulated the proliferation of PTCs. 10(-11)
      M ANG II stimulated Na+ uptake by 20%, whereas 10(-9) M ANG II inhibited it by
      20% (p < 0.05). The stimulatory effect of 10(-11) M ANG II on Na+ uptake was
      inhibited by amiloride (10(-3) M) and by losartan (ANG II receptor subtype 1
      antagonist, 10(-8) M) but not by PD123319 (ANG II receptor subtype 2 antagonist,
      10(-8) M). Pertussis toxin (PTX, 50 ng/ml) prevented the ANG II-induced
      stimulation of Na+ uptake (p < 0.01). 8-Bromoadenosine 3', 5'-cyclic
      monophosphate (8-Br-cAMP, 10(-6) M) did not affect Na+ uptake. SQ 22536
      (adenylate cyclase inhibitor, 10(-6) M) also did not change the ANG II-induced
      stimulation of Na+ uptake. ANG II did not stimulate cAMP production. In contrast,
      12-O-tetradecanoylphorbol-13-acetate (TPA, 0.01 ng/ml) produced significant
      increase in Na+ uptake. When ANG II and TPA were added together to the PTCs,
      there was no additive effect on Na+ uptake. Staurosporine (calcium-dependant
      protein kinase C inhibitor, 10(-6) M) led to a complete inhibition of ANG II
      induced stimulation of Na+ uptake. ANG II-treatment resulted in a 26% increase in
      total protein kinase C (PKC) activity. However, 10(-11) M ANG II did not change
      [Ca2+]i mobilization and [3H]-AA release while 10(-9) M ANG II increased both of
      them. In conclusion, the PTX-sensitive PKC pathway may be the main signaling
      cascade in the stimulatory effects of low dose of ANG II (10(-11) M) on Na+
      uptake in the primary cultured rabbit renal proximal tubule cells in hormonally
      defined serum-free medium.

PMID- 10081752
TI  - Effects of maternal acetazolamide treatment on body weights and incisor
      development of the fetal rat.
AB  - The incisor development of fetal rats on gestation day 19 was well correlated
      with their fetal weights. The number of odontoblasts in the mandibular incisors,
      an index of incisor development, increased more than that of the maxillary
      incisors with increase in fetal body weights. Maternal acetazolamide treatments
      were observed to suppress the mean fetal weight and to retard incisor
      development. A smaller incisor size, a thinner predentin layer, and fewer
      odontoblasts were characteristic of the acetazolamide group. There was also a
      good correlation between the fetal weights and the number of odontoblasts in the
      acetazolamide group. From these results, we postulated that the retarded incisor
      development of the fetal rats caused by the maternal acetazolamide treatment was
      related to their suppressed fetal weights. However, the regression coefficient of
      the fetal weights and the number of odontoblasts in the acetazolamide group was
      smaller than that of the vehicle control group. It may indicate that retarded
      incisor development in response to maternal acetazolamide treatment is to some
      extent independent of suppressed fetal weight.

PMID- 10081753
TI  - Apoptosis of villous epithelial cells and follicle-associated epithelial cells in
      chicken cecum.
AB  - The process of the disappearance of epithelial cells was examined in chicken
      cecal villi and follicle-associated epithelium (FAE). The apoptotic epithelial
      cells with intense DNA-fragmentation and their exfoliation were found in the
      villous tips. The epithelial cells with weak DNA-fragmentation were seen in the
      upper portion of the villi and their sparse exfoliations were also found there.
      Numerous epithelial cells in the intestinal lumen expressed the apoptotic
      features. A row of apoptotic epithelial cells with DNA-fragmentation was also
      found in the apical FAE, whereas no M cells exhibited any apoptotic signs. In all
      cecal regions, CD3+, CD8+, and TCR2+ lymphocytes were predominant in the
      epithelium at the upper portion of the villi and the FAE. CD4+ lymphocytes were
      mainly seen in the lamina propria. TCR1+ lymphocytes were not abundant in
      comparison with TCR2+ lymphocytes in the epithelium. TCR3+ T lymphocytes were
      rarely detected. These results suggest that the chicken cecal epithelial cells
      exfoliated into the lumen after the induction of the apoptosis, and that the
      induction may be involved with CD3+, CD8+, and TCR2+ lymphocytes. No death in M
      cells suggests that M cells may transform into microvillous epithelial cells.

PMID- 10081754
TI  - Effects of respiratory cycle on pulmonary venous flow and cardiac cycle on
      pulmonary venous diameter of dogs: a transesophageal echocardiography study.
AB  - We investigated 12 anesthetized normal dogs using transesophageal
      echocardiography to understand the effects of respiration on the pulmonary venous
      flow. Additionally, we observed whether the diameter of the pulmonary vein
      changes with the heart beat. The pulsed Doppler wave form of pulmonary venous
      flow predominantly demonstrated two backward flows, with one peak occurring
      during ventricular systole and another during ventricular diastole. Sometimes a
      small forward flow occurred during left atrial contraction. In comparison with
      expiration, the peak velocity and velocity-time integral of the flow wave under
      inspiration occurred during both systole and diastole were significantly smaller.
      The diameter of the pulmonary vein decreased during left atrial contraction and
      increased during left ventricular systole and diastole.

PMID- 10081755
TI  - Non-purulent meningoencephalomyelitis of a Pacific striped dolphin
      (Lagenorhynchus obliquidens). The first evidence of morbillivirus infection in a
      dolphin at the Pacific Ocean around Japan.
AB  - On March 22, 1998, a mature, male, hyposthenic Pacific striped dolphin
      (Lagenorhynchus obliquidens) was stranded at Aoshima Beach in Miyazaki
      prefecture, Japan. A necropsy performed 14 hr after death revealed mild diffuse
      congestion and edema of the leptomeninges and mild pulmonary atelectasis.
      Histopathologically, non-purulent inflammatory were observed throughout the
      cerebrum, thalamus, midbrain, pons, medulla oblongata, and spinal cord.
      Hematoxylin and eosin stain revealed no viral inclusion bodies.
      Immunohistochemistry using a monoclonal antibody against nucleoprotein of canine
      distemper virus (CDV-NP) revealed a number of CDV-NP-positive granular deposits
      in the cytoplasm and cell processes of the degenerating or intact neurons. The
      present paper is a first report of spontaneously occurred morbillivirus infection
      in a dolphin at the Pacific Ocean around Japan.

PMID- 10081756
TI  - Pulmonary lesions in guinea pigs experimentally infected with Actinobacillus
      pleuropneumoniae (A.p.) serovar 1.
AB  - Pathological studies were carried out on the lungs of guinea pigs intratracheally
      inoculated with 4.6 x 10(6-8) colony forming units (CFU)/head of Actinobacillus
      pleuropneumoniae serovar 1. All animals in the highest dose group died within 24
      hr post inoculation (hpi) and showed pulmonary lesions being hemorrhagic in
      nature while all animals in the lowest dose group were killed as scheduled at 11
      days post inoculation (dpi) and showed only hyperplasia of peribronchial lymphoid
      tissues. In the middle dose group, two died within 24 hpi, two died at 9 dpi, and
      the remaining one was killed at 11 dpi. Two guinea pigs which died at 9 dpi
      showed fibrinonecrotic pleuropneumonia which is the most characteristic acute
      pulmonary lesion in swine, and has not yet been reproduced in laboratory animals
      up to the present time. This suggests that guinea pigs may be a useful laboratory
      animal for studying the pathogenesis of Actinobacillus pleuropneumoniae infection
      in swine.

PMID- 10081757
TI  - The effect of motilin on the regulation mechanism of intestinal motility in
      conscious horses.
AB  - Laparotomy was performed on seven thoroughbreds to attach a force transducer to
      the proximal jejunum, distal jejunum, and ileum, as well as to the serous
      membrane of the cecum. Following observation of intestinal motility in conscious
      horses, they were intravenously injected with motilin (0.6 microgram/kg) to
      examine its effect on intestinal motility. Strong contractions peculiar to horses
      were observed in small intestine. Further, motilin caused strong contractions in
      the proximal jejunum. The results suggested the involvement of motilin in the
      regulation mechanism of intestinal motility.

PMID- 10081758
TI  - Expression of bovine cytokines in Escherichia coli.
AB  - Glutathione S-transferase fusion proteins of bovine interleukin-2 (IL-2), IL-4,
      IL-6 and interferon-gamma (IFN-gamma) were expressed in Escherichia coli.
      Complementary DNA (cDNA) for open reading frame of each cytokine without signal
      peptide encoding region was amplified by reverse transcriptional polymerase chain
      reaction method and was subcloned into pGEX-5X-1. In result, IL-6 and IFN-gamma
      fusion proteins in bacteria were soluble, but IL-2 and IL-4 fusion proteins were
      insoluble. The insoluble IL-2 fusion protein successfully refolded by urea became
      soluble. The recombinant IL-2, IL-6 and IFN-gamma could be obtained by the batch
      method using Glutathione Sepharose 4B and Factor Xa digestion, which may be
      useful for preparation of antisera as antigens and functional studies.

PMID- 10081759
TI  - Hemorrhagic enteritis associated with Clostridium perfringens type A in a dog.
AB  - A female Shetland sheep dog died suddenly with hemorrhagic diarrhea and
      vomitting, and was examined pathologically and microbiologically. Gross
      pathological change was restricted to the intestinal tract. The intestine
      contained watery, blood-stained fluid. Histopathologically, the principal
      intestinal lesion was superficial mucosal hemorrhagic necrosis at the
      jejunoileum. Many Gram-positive bacilli were found adhering to the necrotic
      mucosal surface in parts of the intestinal tract. Clostridium perfringens in pure
      culture were isolated from jejunal contents by anaerobic culture. These results
      suggested that the typical lesion of this case coincided with canine hemorrhagic
      enteritis and enterotoxemia due to C. perfringens infection could be the cause of
      sudden death.

PMID- 10081760
TI  - Duration of antibodies against 24 kd protein of Rhipicephalus sanguineus extract
      in dogs infested with the adult ticks.
AB  - A 24 kd protein from Rhipicephalus sanguineus (Rs24p) which was common to larvae,
      nymphs, male and female whole body and salivary gland extract of males and female
      was detected specifically in the serum from dogs after repeated infestation with
      adult R. sanguineus. The duration of antibodies against Rs24p in dogs infested
      with adults was examined by Western blotting analysis. Anti-Rs24p antibody was
      detected in two of 4 dogs during the period of 40 days in the first infestation.
      In the second infestation, all dogs showed positive reaction against Rs24p, but
      the duration of the antibodies varied greatly among the animals.

PMID- 10081761
TI  - Changes in hyaluronidase, acrosin, and N-acetylhexosaminidase activities of dog
      sperm after incubation.
AB  - Hyaluronidase, acrosin and N-acetylhexosaminidase activities were examined in
      sperm collected from 12 beagle dogs and in culture medium after 0.5 hr and 7 hr
      of sperm incubation. The activities of the three enzymes were significantly
      higher at 7 hr than at 0.5 hr (P < 0.05, 0.01), and the increases were associated
      with sperm capacitation. It was considered that the three enzymes in the dog
      sperm are related to fertilization by reason of the findings of the release of
      these enzymes from the sperm into the medium after 7 hr of incubation.

PMID- 10081762
TI  - Amplification of the c-yes oncogene in canine mammary tumors.
AB  - Genomic DNAs of 14 mammary tumors were analyzed by Southern blot hybridization
      using a human c-yes-1 oncogene probe. The amplification was successful in half of
      the cases (7 adenocarcinomas). The degree of amplification was approximately 4
      fold, and a high proportion was seen in malignant tumors. In addition, DNA
      polymorphism was detected in two adenocarcinomas.

PMID- 10081763
TI  - Malignant basal cell tumor in a Djungarian hamster.
AB  - A malignant basal cell tumor was found in the skin of the abdomen of a female
      Djungarian hamster of unknown age and weighing 40 g. Histologically, the tumor
      mass was composed of cells resembling the basal cells of the epidermis, and these
      cells exhibited solid type proliferation. In the tumor tissue and necrotic foci,
      horn cysts were observed. Immunohistochemically, cytokeratin was present in the
      tumor cells and horncysts. By electron microscopic examination, the tumor cells
      had scanty cell organelles and a few desmozomes. This paper describes a rare
      malignant basal cell tumor in a Djungarian hamster.

PMID- 10081764
TI  - A modified immunoperoxidase assay for detection of antibody porcine reproductive
      and respiratory syndrome (PRRS) virus in swine sera.
AB  - MARC-145 cell monolayers infected with PRRS virus were fixed in 3% neutral
      buffered formalin and embedded in paraffin. The sections were stained by avidin
      biotin complex immunoperoxidase (ABC) method. Test sera were applied to sections
      as primary antibodies. The positive reactions were detected by ABC method and
      indirect immunofluorescent assay (IFA). There was good correlation between ABC
      and IFA, and the titers in ABC were higher than those in IFA. The present results
      indicate that the immunohistochemical staining is a useful test for the detection
      and quantitation of PRRS virus antibody in swine sera as well as IFA.

PMID- 10081765
TI  - Feline immunodeficiency virus subtype C is prevalent in northern part of Taiwan.
AB  - The seroepidemiological survey of cats conducted in northern part of Taiwan in
      1998 revealed that the positive rate of feline immunodeficiency virus (FIV)
      infection was 21.9% (7/32) and the rate was much higher than those of previous
      reports. We succeeded in isolation of three strains of FIV from peripheral blood
      mononuclear cells of the blood samples. Nucleotide sequences of the env variable
      V3 to V5 region of the strains revealed that the isolates from distinct areas
      belong to subtype C. These data together with our previous report (Inada et al.
      1997. Arch. Virol., 142: 1459-1467) indicate that FIV subtype C is prevalent in
      northern part of Taiwan.

PMID- 10081766
TI  - T cell subset involvement in immune responses to Fasciola hepatica infection in
      cattle.
AB  - The lymphocyte response to F. hepatica during a primary infection in cattle was
      analysed to define the role of T cell subsets in the immune response. Blood
      lymphocytes were isolated from eight cattle infected with F. hepatica via trickle
      infection over a ten-day period and from two non-infected controls. CD4+, CD8+
      and gamma delta + T cells were depleted from whole lymphocyte populations by
      magnetic bead depletion. Lymphocytes from infected animals demonstrated a
      transient, but marked elevation in responsiveness to F. hepatica antigen between
      weeks 3 and 8 post-infection. Responses were attenuated by depletion of CD4+ and
      CD8+ T cells during this period. Depletion of gamma delta + T cells attenuated
      antigen responses at one time point only, and at an earlier stage post-infection
      than when alpha beta + T cells were depleted. Responses to antigen correlated
      positively with both hepatic fluke burden and with the degree of hepatic damage.
      This suggests that the cellular immune response was not protective. Antigen
      responses in gamma delta + T cell-depleted populations were also associated with
      post-mortem fluke burden and with hepatic damage. This suggests that gamma delta
      + T cells are involved in down regulating alpha beta + lymphocytes which may have
      a role in a non-protective or immunopathological immune responses.

PMID- 10081767
TI  - Definition and mapping of epitopes recognized by specific monoclonal antibodies
      to Schistosoma bovis 28 kDa glutathione S-transferase: relation with anti-egg
      viability immunity.
AB  - Monoclonal antibodies to the 28kDa glutathione S-transferase of Schistosoma bovis
      have been constructed in mice and used to characterize the epitope(s) potentially
      implied in the induction of anti-fecundity and anti-egg viability immune
      responses. Among the MoAbs produced three were particularly studied: Sb4-50
      (IgG2a) and Sb4-56 (IgG1) which inhibited Sb28GST activity and Sb4-10 (IgG1)
      which did not. The use of overlapping peptides covering the entire amino acid
      sequence of Sb28GST, allowed us to define the linear epitopes recognized by these
      anti-Sb28GST MoAbs. Amino acid residues 202-211 were recognized by both MoAbs Sb4
      50 and Sb4-56 and MoAb Sb4-10 recognized amino acid residues 58-67. Their
      capacity to inhibit GST activity suggested binding to the active site or to
      neighbouring regions, which include the C-terminal domain (a.a. 190-211) of the
      protein. When passively transferred into BALB/c mice MoAbs induced a significant
      reduction in egg hatching and an increase in immature eggs. Effects on worm
      burdens were, however, variable and no clear-cut association between the
      inhibition of enzyme activity and anti-fecundity or anti-viability activities was
      recorded. Our data indicate that beside the anti-fecundity and anti-viability
      immunity related to the impairment of GST activity, immune response to epitopes
      located in other regions of the molecule also contribute to the reduction of egg
      viability.

PMID- 10081768
TI  - Antibody and Th1/Th2-type responses in BALB/c mice inoculated with live or dead
      Echinococcus granulosus protoscoleces.
AB  - The aims of this study were to investigate whether a Th1- or a Th2-type response
      is stimulated in the first stages of experimental infection with Echinococcus
      granulosus, and to determine whether live or dead protoscoleces equally
      contribute to such Th1/Th2-type polarization. Live parasites stimulated the
      production of IL-10, IL-4 and IL-5 as early as week 1 postinoculation. The levels
      of IL-10 and IL-4 decreased towards week 4 p.i. and that of IFN gamma increased.
      The production of specific antibodies was characterized by high levels of
      systemic IgG1 and local IgM and IgG3 (measured in peritoneal lavages). In
      contrast, dead parasites induced elevated levels of IL-4, IFN gamma, IL-10 and IL
      5 on week 1 postinoculation followed by a decrease of IFN gamma and an increase
      of IL-4. Low levels of specific antibodies were stimulated by dead parasites both
      systemically and in the peritoneal cavity. These results show that E. granulosus
      infection induced an early Th2-type response and that live parasites stimulated
      stronger antibody responses than dead parasites. In addition, they strongly
      suggest that both phenomena were modulated by live protoscoleces.

PMID- 10081769
TI  - Echinococcus granulosus human infection stimulates low avidity anticarbohydrate
      IgG2 and high avidity antipeptide IgG4 antibodies.
AB  - Total IgG and IgG subclasses recognizing carbohydrate and peptidic epitopes from
      native and periodate treated partially purified hydatid cyst fluid (ppHCFA) and
      protoscolex somatic antigens (PSA) were tested by ELISA in hydatid patients sera.
      Binding of the major cross-reactive antiphosphorylcholine antibodies was
      inhibited with free reagent. A predominant anticarbohydrate antibody response
      against ppHCFA and PSA is shown. Although the main contributing IgG subclass to
      the antipeptide response against both antigens was IgG4, IgG1 also significantly
      contributed to the anti-PSA peptidic epitopes response. Western blot showed that
      IgG1 antibodies strongly recognized in ppHCFA a periodate susceptible 38 kDa
      antigen. The IgG4 antibodies mainly recognized the periodate-resistant 12, 16 and
      24 kDa antigens. In addition, IgG2 antibodies recognized three strongly periodate
      susceptible broad bands (116, 55 and 24 kDa antigens). PSA-specific IgG1 and IgG4
      antibodies showed similar patterns of antigen recognition as well as no
      significant reduction of reactivity after periodate treatment while the IgG2
      antibody recognition was strongly affected by this treatment. Furthermore, IgG2
      showed significantly lower avidities than IgG1 and IgG4 antibodies recognizing
      both antigens. In conclusion, hydatid patients showed an enhanced production of
      low avidity anticarbohydrate IgG2 as well as high avidity antipeptide IgG4
      antibodies.

PMID- 10081770
TI  - Mosquito feeding modulates Th1 and Th2 cytokines in flavivirus susceptible mice:
      an effect mimicked by injection of sialokinins, but not demonstrated in
      flavivirus resistant mice.
AB  - Culex pipiens and Aedes aegypti mosquitoes were fed on C3H/HeJ mice and systemic
      cytokine production was quantified from stimulated lymphocytes harvested four to
      ten days after feeding. Mosquito feeding on C3H/HeJ mice significantly down
      regulated IFN gamma production seven to ten days post feeding by Cx. pipiens and
      seven days after Ae aegypti feeding. Th2 cytokines, IL-4 and IL-10, were
      significantly up regulated 4-7 days after Cx. pipiens and Ae. aegypti feeding.
      The immunosuppressive effect of Cx. pipiens feeding on systemic cytokine
      production was not evident in congenic flavivirus resistant (C3H/RV) mice, as
      systemic IFN gamma and IL-2 were significantly up regulated at days 7 and 10,
      correlating with a significant decrease in IL-4 10 days after feeding by Cx.
      pipiens mosquitoes. Inoculation of 5-1000 ng of sialokinin-I into C3H/HeJ mice
      mimicked the effect of Ae. aegypti feeding by down regulating Th1 cytokines and
      significantly up regulating Th2 cytokines four days post inoculation. Injections
      of sialokinin-II resulted in only moderate effects on IFN gamma and IL-4
      production seven and ten days after injection. Thus natural feeding by two
      arbovirus vectors had a profound T cell modulatory effect in vivo in virus
      susceptible animals which was not demonstrated in the flavivirus resistant host.
      Moreover, sialokinin-I and sialokinin-II mimicked the effect of mosquito feeding
      by modulating the host T cell response. These results may lend new insight into
      specific aspects of the role of the mosquito vector in potentiating virus
      transmission in the mammalian host.

PMID- 10081771
TI  - Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not
      critical in resistance to Trichuris muris.
AB  - The murine intestinal nematode Trichuris muris provides an invaluable model of
      human infection with T. trichiura. Hence, analysis of the immunological responses
      in the mouse may elucidate the mechanisms of immunity to trichuriasis in man. The
      work described here investigates the roles of eosinophils, mast cells and
      antibody-dependent cell-mediated cytotoxicity (ADCC) in the elimination of T.
      muris from the host gut. Following ablation of IL-5, and hence eosinophilia, mice
      usually resistant to T. muris infection remained so. Further, blocking the stem
      cell factor receptor, c-kit, to facilitate complete ablation of mast cells over
      the period of parasite expulsion in resistant mice had no effect on the
      development of protective immunity. Therefore it can be deduced that eosinophils
      and mast cells are not critical in resistance. In addition to these studies, the
      role of antibody-mediated cellular cytotoxic mechanisms was investigated via the
      analysis of an infection time course in Fc gamma R-/- mice. These animals, on a
      resistant background, were fully immune and expelled the parasites before
      development of the adult stage. Thus this model provides evidence against a major
      role for ADCC in resistance to infection with T. muris. The studies described
      here have eliminated some of the major effector mechanisms traditionally
      associated with helminth infection, and work continues to elucidate the critical
      immune responses associated with resistance.

PMID- 10081772
TI  - DNA immunization by intramuscular injection or gene gun induces specific IgG
      antibodies against a Schistosoma japonicum 22 kDa antigen, Sj22, when fused to
      the murine Ig K-chain secretory leader sequence.
AB  - The 22 kDa tegumental surface membrane-associated antigen of Schistosoma
      japonica, Sj22, is of recognized interest in schistosomiasis vaccine research.
      However, previous attempts to induce antibody responses against Sj22 by DNA
      immunization have been unsuccessful. In this report we demonstrate that fusing
      the Sj22 cDNA to the murine immunoglobulin Ig kappa-chain secretory leader
      sequence results in the generation of antigen-specific IgG antibodies following
      DNA immunization. Mice were immunized into the skin with DNA-coated gold
      microspheres using a gene-gun, or into the quadriceps muscle by intramuscular
      injection. Both methods of delivery generated antigen-specific IgG antibodies
      against the 22 kDa schistosome antigen. The use of a secretory leader sequence,
      such as the murine Ig-kappa chain used in this study, may facilitate the
      induction of host antibody responses following DNA immunization with other
      parasite cDNAs.

PMID- 10081773
TI  - [Molecular and cellular pathophysiology of sickle cell anemia].
AB  - The beta S mutation responsible for sickle cell disease (SCD) was identified in
      1949. This mutation always consists in a T for A substitution at codon 6 of the
      beta-globin chain. Deoxygenated HbS becomes polymerized, producing erythrocyte
      shape changes and vasoocclusion. Still unexplained is the wide variability in
      clinical expression of SCD, whose spectrum ranges from severely incapacitating
      forms to virtually silent forms. Recent research has focused on genetic or
      environmental factors that may interfere with one or more steps of the basic
      pathophysiologic mechanisms. These factors can be roughly classified in three
      groups: i) factors that modify HbS levels within erythrocytes, thereby impacting
      the propensity of HbS for polymerization; ii) other normal or abnormal
      hemoglobins present in the erythrocyte that may modify side contacts of the
      hemoglobin molecule within the polymer, thus either stopping or enhancing
      polymerization; iii) molecules other than hemoglobin expressed at the surface of
      the SCD reticulocytes that may adhere to the vascular endothelium, thus slowing
      flow in the microcirculation and delaying HbS reoxygenation. Whatever the
      starting point, the same vicious circle is set in motion. These mechanisms have
      generally been studied separately, in vitro, under artificial conditions. An
      important goal is to understand how they interact in vivo in a given patient.

PMID- 10081774
TI  - [Neonatal screening for sickle cell anemia in metropolitan France. For the group
      for neonatal screening of sickle cell anemia of the French Association for
      Screening and Prevention of Infant Handicaps (AFDPHE)].
AB  - An experimental neonatal screening program for sickle cell disease (SCD) was set
      up in continental France in 1990. The screening strategy was fine-tuned based on
      results of screening programs in the French West Indies and of pilot studies in
      several regions of continental France. Since early 1994, sickle cell disease
      screening is done in combination with screening for phenylketonuria,
      hypothyroidism, and congenital adrenal hyperplasia but is restricted to infants
      identified by maternity units as belonging to high-risk ethnic groups. Cost has
      proved acceptable, and rates of false-positive and false-negative tests have been
      very low. The management of infants with a positive screening test has been
      defined. All cases detected to date have been included in a prospective study.
      SCD is currently being extended to the entire country, an endeavor that will
      require considerable education efforts and careful surveillance.

PMID- 10081775
TI  - [Infection and sickle cell anemia].
AB  - Sickle cell disease is associated with frequent and often severe infections as a
      result of immune function impairment and functional asplenia. Also, infection can
      trigger a vasoocclusive crisis. Pneumococcal bacteremia and meningitis are so
      severe as to warrant prophylactic penicillin therapy, which has provided a
      dramatic decrease in early mortality. Bacterial pneumonia is common in patients
      younger than four years, with most cases being due to S. pneumoniae, Haemophilus
      influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Acute chest syndrome
      is both a difficult differential diagnosis and a common concomitant of bacterial
      pneumonia. Osteomyelitis is generally due to a salmonella, most often S.
      enteritidis; multiple foci are common and treatment is difficult, with some
      patients developing chronic osteomyelitis with sequestration. Parvovirus B 19
      infection causes acute bone marrow failure. Malaria does not result in cerebral
      malaria but can lead to severe anemia or vasoocclusive crisis, and should
      therefore be effectively prevented. Antimicrobials are generally selected for
      efficacy against pneumococci (septicemia, meningitis), Salmonella (septicemia,
      meningitis, osteomyelitis), and mycoplasmas (pneumonia). Prophylactic therapy is
      of paramount importance and relies on long-term or lifelong penicillin therapy
      started at four months of age and on closely-spaced immunizations, most notably
      against pneumococci, the hepatitis B virus, S. typhi, and H. influenzae.
      Resistant pneumococcal strains have not been reported to cause prophylactic
      treatment failures. Conjugated pneumococcal vaccines are effective in protecting
      infants and should therefore be used in sickle cell patients.

PMID- 10081776
TI  - [Pathophysiology of acute thoracic syndrome].
AB  - Pulmonary complications are the leading cause of morbidity and mortality in
      sickle cell disease patients. Acute chest syndrome (ACS), in which chest pain and
      dyspnea, occurs in combination with a recent chest radiograph abnormality, raises
      both diagnostic and therapeutic challenges. The pathogenesis of ACS involves
      alterations in blood rheology, increased coagulability, and, above all, increased
      adhesion of sickle cells to the vascular endothelium and nitric oxide-mediated
      dysregulation of vascular reactivity. Sickle cell disease thus impacts all the
      cells in the vascular environment. Recently gained insights into pathophysiology
      offer hope that new treatments for preventing and treating acute and chronic
      pulmonary complications will soon become available.

PMID- 10081777
TI  - [Imaging of cerebrovascular disease in sickle cell anemia].
AB  - Cerebral vascular disease is a common and serious complication of sickle cell
      disease that mainly involves the large blood vessels of the skull base. Because
      recurrences are common and residual deficits severe, attention has turned to
      detection of preclinical cerebral involvement with the goal of preventing
      clinical damage. Magnetic resonance imaging (MRI), an extremely sensitive tool
      for detecting cerebral infarction/ischemia, has shown that 10% of asymptomatic
      patients exhibit white matter lesions that seem to be associated with impaired
      cognitive function and may be predictive of stroke; magnetic resonance
      angiography demonstrates occlusions of skull base arteries but is not reliable
      for the diagnosis of stenosis because of artifacts generated by rapid turbulent
      flow. Transcranial Doppler is sensitive and specific for the detection of
      arterial stenosis and occlusion, even in asymptomatic patients. Digitized
      cerebral angiography remains the gold standard investigation for pretreatment
      confirmation of lesions detected by Doppler and/or MRI.

PMID- 10081778
TI  - [Management of adults with sickle cell anemia].
AB  - The management of adults with sickle cell disease should be geared to the profile
      of the disease in adulthood. The chronic hemolytic anemia impacts everyday
      activities. Paroxysmal complications include painful vasoocclusive crises, acute
      chest syndrome, priapism, and infections. Potentially life-threatening chronic
      complications should be detected and treated early; they include cardiopulmonary,
      renal, and hepatic involvement. Osteonecrosis of the hip can result in functional
      impairment. Pregnancy and anesthesia require special precautions. A multifaceted
      personalized management program, if possible at a sickle cell disease center
      working closely with other health care providers and social workers, offers the
      best hope for providing ever-increasing gains in quality of life for sickle cell
      disease patients.

PMID- 10081779
TI  - [Sickle cell anemia and pregnancy. Complications and management].
AB  - An increasing number of sickle cell disease patients are deciding to bear
      children. The high risk of fetal and maternal complications in pregnant sickle
      cell disease patients mandates multidisciplinary management. Risks include
      spontaneous abortion, vasculorenal syndrome, fetal growth retardation, and fetal
      death in utero. The rates of cesarean section, maternofetal infection, and
      maternal death are higher than in the population at large. The diagnosis should
      be made prior to conception or during early pregnancy. Frequent visits with the
      obstetrician, hematologist, and anesthesiologist/intensivist are mandatory.
      Exchange transfusion or blood transfusion may be indicated in patients with a
      history of serious obstetrical or hematologic complications. Risks are highest in
      late pregnancy, during delivery, and in the postpartal period. However, the
      entire pregnancy is a high-risk period that warrants close monitoring.

PMID- 10081780
TI  - [Hydroxyurea and other agents stimulating synthesis of fetal hemoglobin].
AB  - Five years after the initiation of the first clinical trials of hydroxyurea in
      pediatric sickle cell anemia patients, there is firm evidence that this drug
      induces a significant and sustained increase in fetal hemoglobin (HbF) production
      and decreases the frequency of vasoocclusive crises in the overwhelming majority
      of cases. The mean dosage associated with clinical benefits is 20 mg/kg/d; the
      HbF increase is not perfectly correlated with clinical benefits, so that a dosage
      increase should be considered based on the absence of a clinical improvement
      after three months. The daily dose should not exceed 40 g/kg. Short- and medium
      term safety has been acceptable, with the few episodes of bone marrow toxicity
      resolving after dose attenuation or temporary drug discontinuation. Many issues
      remain unsettled, most notably the long-term safety of this cytostatic
      medication. Current knowledge gaps should be fully disclosed to parents, and
      hydroxyurea therapy should be reserved for patients with severe pain. Because no
      randomized placebo-controlled trials are available, the potential role for
      hydroxyurea as a preventive or curative treatment for other complications of
      sickle cell disease remains unknown.

PMID- 10081781
TI  - [Results and current indications of bone marrow allograft in sickle cell
      disease].
AB  - Since 1988, 34 pediatric patients with severe sickle cell disease have received
      bone marrow transplantation (BMT) from HLA-identical siblings in France. After
      1992, documentation of the favorable effect of hydroxyurea therapy on the
      frequency of vasoocclusive crisis (VOC) left a history of stroke (n = 16) as the
      main indication for BMT. Among patients treated by genoidentical BMT, 85% were
      cured and 9% died. All deaths were due to severe graft-versus-host disease. The
      rejection rate fell from 25% to 5% after addition of ATG to the conditioning
      regimen. BMT reversed some sickle cell disease-related abnormalities: splenic
      function improved and some cases of osteonecrosis showed a favorable course.
      Fifteen of 16 patients with a history of stroke showed no stroke recurrence after
      BMT, and arterial stenoses improved. BMT should be offered to sickle cell anemia
      patients with a history of stroke if a genoidentical donor is available. To
      prevent stroke-related residual impairment and transfusion-related complications,
      BMT should be considered early in patients with Doppler or MRI evidence of silent
      stroke associated with cognitive function impairment, failure to respond to
      hydroxyurea therapy (frequent VOCs, severe anemia and thrombocytosis, multifocal
      osteonecrosis), or polyerythroalloimmunization. Storage of frozen of cord blood
      samples from siblings should be considered.

PMID- 10081782
TI  - [Transfusion in sickle cell anemia].
AB  - Although blood transfusion (BT) therapy remains a key component of the weaponry
      used to treat acute and chronic sickle cell disease complications, its
      indications and modalities are currently the focus of a critical reappraisal
      prompted by the introduction of hydroxyurea, recent improvements in allogeneic
      bone marrow transplantation, and increasing attention to safety concerns.
      Expected benefits of each BT should be carefully weighed against the risks of
      infections, immunologic complications, and iron overload. Simple or exchange BT
      can be used. In emergency situations, the only effective means of improving
      tissue oxygenation and limiting blood vessel occlusion is dilution or removal of
      HbS by simple or exchange BT, respectively; simple BT is indicated in severe
      anemia or acute hypovolemia and exchange BT in acute vasoocclusive crisis or
      acute infection. In nonemergency situations, long-term exchange BT programs
      geared to maintain the HbS level around 30% are used to stabilize existing
      lesions and to prevent recurrences; they have been proved effective in preventing
      recurrent stroke in patients who are not candidates for allogeneic bone marrow
      transplantation. Situations in which BT therapy is widely used despite
      controversy regarding its value and modalities include the prevention of
      complications of pregnancy, the prevention of perioperative complications, and
      the prevention of recurrences of severe vaso occlusive crisis in patients
      eligible for hydroxyurea therapy. Advances have been made in the minimization of
      BT-related complications (alloimmunization, viral infections, iron overload)
      through critical appraisal of the need for each BT, careful selection of the most
      appropriate blood product, and a change in BT technique resulting in a reduction
      in the number of blood donors.

PMID- 10081783
TI  - [The bronchorelaxant effect of helicidine, a Helix pomatia extract, interferes
      with prostaglandin E2].
AB  - Helicidine is a biological extract prepared from the snail Helix pomatia L. and
      used in man as an anti-tussive agent. However, its mechanisms of action are not
      fully defined. In this study, we have investigated a possible relaxant effect of
      helicidine on guinea-pig airway smooth muscle and evaluated the role of
      prostanoids and airway epithelium in this relaxation. H. pomatia extract (0.001-1
      mg/ml) induced a dose-dependent relaxation of guinea-pig trachea pre-contracted
      with histamine both in the presence and absence of tracheal epithelium. No
      significant difference in dose-dependency or magnitude of the relaxation was
      observed between tracheal segments with or without epithelium (maximal relaxant
      response of 35 +/- 7 and 25 +/- 7.5%, respectively). Relaxation of the trachea
      induced by H. pomatia extract (0.001-1 mg/ml) was inhibited by pre-treatment with
      the cyclooxygenase inhibitor, indomethacin, both in the presence or absence of
      tracheal epithelium. H. pomatia extract (1 mg/ml) induced a marked and
      significant increase in prostaglandin E2 release in tracheal segments with and
      without epithelium. These results indicate that helicidine possesses a broncho
      relaxant activity which is independent of epithelium integrity and which is
      partly mediated by the release of the relaxant prostanoid, prostaglandin E2. The
      origin of prostaglandin E2 production in the airways remains to be defined.

PMID- 10081784
TI  - An on-farm study of the epidemiology of Actinobacillus pleuropneumoniae infection
      in pigs as part of a vaccine efficacy trial.
AB  - Thirty cohort pigs were followed from birth to slaughter to study epidemiological
      patterns of porcine pleuropneumonia caused by Actinobacillus pleuropneumoniae.
      The study was conducted within a larger 380-animal study of vaccination against
      Mycoplasma hyopneumoniae and A. pleuropneumoniae in a 340-sow farrow-to-finish
      piggery with 4-month weaning, operating a continuous system of intensive
      production in the North Island of New Zealand. The cohort pigs were randomly
      allocated into two equal groups: vaccinated and control. Pigs in the first group
      were vaccinated at 2 and 4 weeks of age with both M. hyopneumoniae vaccine and A.
      pleuropneumoniae vaccine at separate vaccination sites. A series of nasal swabs
      was taken at 4, 8, 10, 11, 12, 14, 16 and 18 weeks of age. Each swab was streaked
      onto the surface of a selective medium on the farm and the plates were
      immediately transported to a laboratory and incubated at 37 degrees C for 5 days.
      After the trial, pigs were slaughtered at an average of 132 days of age, lungs
      were examined and samples taken for bacteriological culture and isolation. Thirty
      five out of 256 samples produced haemolytic colonies which were Gram-negative, V
      factor-dependent and positive to the CAMP test. A. pleuropneumoniae was first
      isolated at 4 weeks of age from one vaccinated pig. This finding suggests that
      piglets became infected in the farrowing pen and the source of infection might be
      a carrier sow. The interval-specific cumulative incidence of A. pleuropneumoniae
      infection reached a maximum of 54% and 40% at 11 weeks of age in the vaccinated
      and control groups, respectively. Infection status of the litter is considered to
      be a factor influencing morbidity in infected herds during weaner and grower
      periods. Our results suggest that simultaneous vaccination with M. hyopneumoniae
      and A. pleuropneumoniae vaccines at 2 and 4 weeks of age might lessen the
      prevalence but cannot absolutely prevent A. pleuropneumoniae infection during the
      weaner or grower-finisher periods.

PMID- 10081785
TI  - Field efficacy of a combined use of Mycoplasma hyopneumoniae and Actinobacillus
      pleuropneumoniae vaccines in growing pigs.
AB  - The effectiveness of simultaneous administration of commercial Mycoplasma
      hyopneumoniae and Actinobacillus pleuropneumoniae vaccines was tested in an
      indoor commercial piggery which had experienced continuing respiratory-disease
      problems confirmed as due to both of these pathogens. Piglets were randomly
      assigned in equal numbers to vaccination and control groups, and each vaccine was
      administered at a separate site to assigned piglets at two and four weeks of age.
      Live weight of vaccinates immediately prior to slaughter was 2.49 kg higher (p =
      0.04) than for controls at equal mean slaughter age of 132 days. Average daily
      gain (ADG) from 16 weeks to slaughter of vaccinates was also significantly higher
      (33 g/day) than in controls (p = 0.05). Daily gain was not significantly
      different in younger age groups. Active enzootic pneumonia lesions were more
      likely in control than in vaccinated pigs. There were no significant differences
      between vaccination groups with regard to severity of pleurisy or presence of
      pleuropneumonia lesions at slaughter. Log-linear modelling was used to test the
      statistical association between vaccination, enzootic pneumonia lesions, pleurisy
      lesions and pleuropneumonia lesions. It showed a reduction in the severity of
      enzootic pneumonia lesions for vaccinated pigs, and the presence of
      pleuropneumonia lesions increased the likelihood of pleurisy lesions. No other
      association was significant, and no evidence of synergy between the vaccines in
      influencing lesion severity for pleuropneumonia was detected (within the
      limitations set by the trial design).

PMID- 10081786
TI  - The effect of maternally derived immunoglobulin G on the risk of respiratory
      disease in heifers during the first 3 months of life.
AB  - The objectives were to investigate the association between postcolostral serum
      IgG and the development of calf pneumonia, to elaborate the risk factors for
      pneumonia, and to compare the risk factors for clinician- and caregiver-diagnosed
      respiratory disease. In a prospective observational cohort study, 410 heifer
      calves were clinically examined weekly by a veterinarian during their first 3
      months of life. With an initial questionnaire and during these weekly visits,
      management data were collected. A nested matched case-control design was used to
      compare risk factors between 105 calves with respiratory disease and their 59
      control calves from the same initial population. The IgG levels were determined
      from blood samples taken within 2 weeks after colostrum intake. The appropriate
      cutoff point for the postcolostral IgG level to indicate failure of passive
      antibody transfer when predicting pneumonia appeared to be between 800 and 1300
      mg/dl (values < or = the cutoff point indicated failure). Calves with low IgG
      levels had 2-times higher odds of pneumonia than calves with higher IgG
      concentrations. Housing mostly in the presence of adult cattle was a risk factor
      for pneumonia, whereas housing mostly alone in a hutch was protective. Feeding of
      mastitic colostrum was a risk factor for clinician-diagnosed pneumonia in the
      analysis of the cohort study but not in the matched case-control design. There
      was a three-times higher risk of pneumonia if calves were given their dam's
      colostrum for the first feeding and the dam had clinical mastitis at the time of
      first milking. Caregiver- and clinician-diagnosed pneumonia had slightly
      different risk factors which implies that caution should be used when comparing
      studies based on different definitions of pneumonia. The practical implications
      of this study are that more attention should be paid to proper housing conditions
      of the calves in order to reduce incidence of pneumonia.

PMID- 10081787
TI  - Prevalence and risk factors associated with adventitious bursitis in live growing
      and finishing pigs in south-west England.
AB  - The prevalence and risk factors associated with adventitious bursitis in 912
      growing and finishing pigs, originating from 20 different housing systems in
      south-west England, were investigated in this study. The overall prevalence of
      bursal lesions was 63.4%. Bursae were seen at different aspects of the hock:
      lateroplantar, plantar, medial and point of the hock. The most frequently
      affected site was lateroplantar (54.4%) followed by plantar (12.5%), medial
      (2.0%) and finally the point of the hock (0.7%). There was no difference in the
      proportions of left and right hocks affected. Bursal lesions were seen in pigs
      from 8 to 28 weeks of age and prevalence increased with age. Also, the longer the
      period pigs spent in the pen, the more likely they were to have bursitis. After
      accounting for the effect of herd of origin, bedding which covered the whole pen
      (OR 0.11) or only the lying area (OR 0.29) was the most important factor which
      reduced the risk of bursitis. A wet slurry film in the dunging area (OR 1.67) and
      a difference between the solid area and the concrete slats greater than 3 cm (OR
      3.11) were significantly associated with an increased risk of bursal lesions.

PMID- 10081788
TI  - Factors affecting milk urea nitrogen and protein concentrations in Quebec dairy
      cows.
AB  - Milk urea nitrogen (MUN), together with percentage milk protein (PROT), are
      increasingly used as indicators of the protein-energy balance and for monitoring
      nutrition and diagnosing feeding disorders. The goal of this study was to analyze
      the effects of parity, milk yield, days in lactation, somatic-cell count, and
      herd and feeding factors on MUN and PROT. In 10 dairy herds, one milk sample was
      taken from each of 418 cows, within +/- 2 days of the routine milk-test visit. We
      used a four-step multiple linear-regression model with backward elimination,
      including interactions between herd and the different factors. For both dependent
      variables, there were significant interactions with herd. Herd-specific models
      were markedly different; however, the daily amount of protein concentrates fed
      remained (and had a positive coefficient) in seven of 10 herd models for MUN.
      This factor is easy to record under field conditions and has to be considered in
      the evaluation of the ration by means of MUN and PROT. Overfeeding of rumen
      soluble protein can be easily diagnosed and corrected using MUN analyses. The
      relationships between MUN and PROT in respect of the factors parity, daily milk
      yield, and days postpartum also vary considerably among herds.

PMID- 10081789
TI  - The incidence, calf morbidity and mortality due to Theileria parva infections in
      smallholder dairy farms in Murang'a District, Kenya.
AB  - A prospective observational study was conducted among smallholder dairy farmers
      in Murang'a District, Kenya, to estimate the incidence of Theileria parva
      infections, as well as calf morbidity and mortality caused by the infection. The
      study was conducted between March 1995 and August 1996, in five cohorts of female
      calves from birth to six months of age from different agro-ecological zones
      (AEZs) and grazing-system strata shown previously to have varying prevalences of
      T. parva infection. A total of 188 smallholder dairy farms with 225 female calves
      were selected purposively by five AEZ-grazing strata. All recruited calves were
      visited within the first two weeks of life and thereafter at biweekly intervals
      up to the age of six months. The mean number of cattle in these smallholder farms
      was 2.6. Both exotic and indigenous breeds of cattle and their crosses were
      present, with the former predominating. The incidence (27-54%) of sero-conversion
      to T. parva in an ELISA test was significantly different (p < 0.05) across the
      five AEZ-grazing strata and increased with lower elevation and unrestricted
      grazing. Calf morbidity and mortality were also variable across the AEZ-grazing
      strata. East Coast fever (ECF) was the highest-incidence cause calf morbidity and
      mortality (relative to other diseases). There are great differences in the
      epidemiology of ECF within a small area and this implies that there is need to
      carefully consider different ECF control strategies in different AEZ-grazing
      strata.

PMID- 10081790
TI  - Development of a database management/analysis system for field research
      activities within a coordinated research project.
AB  - There are several ways a database/analysis system can assist a scientist engaged
      in field research. Specifically, it can assist the scientist with accurate data
      collection and more rigorous data analyses. The database management portion of
      this system allows accurate data collection and provides easy data entry through
      the use of forms. In addition, it can provide the scientist with structured
      methods of error checking data entry and checking for implausible values and
      false zeros. The system can also assist the scientist with the organization of
      the data and provide easy methods of sorting, grouping, and selecting data for
      analysis. Data can then be exported to a data analysis program where the first
      step is data validation. A menu of analyses using examples from the coordinated
      research project (CRP) are demonstrated using statistical methods that test
      continuous and categorical data.

PMID- 10081791
TI  - Effect of blood metabolites, body condition and pasture management on milk yield
      and postpartum intervals in dual-purpose cattle farms in the tropics of the state
      of Veracruz, Mexico.
AB  - Research was conducted on typical smallholder farms with dual-purpose cattle
      (DPC) (Bos indicus x B. taurus) in the coastal north-central area of Veracruz,
      Mexico. The study was divided into two phases. The aim of the first phase was to
      investigate the effect of blood metabolities, body condition and pasture
      management on milk yield and postpartum intervals, in order to investigate if the
      former are suitable indicators of the reproductive and nutritional status of DPC.
      One hundred and sixty-five calvings of crossbred cows were recorded from January
      1992 to November 1994 on 12 small farms. Milk samples were collected twice a week
      for progesterone analysis. Blood samples and BCS were taken once a month.
      However, in Phase II emphasis was placed on the effect of pasture management upon
      reproductive and productive performance of DPC. Records of four farms were
      obtained from June 1995 to November 1996. Stocking rates were 0.40, 0.87, 0.35
      and 1.5 cows/ha for farms A, B, C and D, respectively. Farms A and C used a slow
      rotation while B and D used a rapid rotation. In Phase I, the changes in BCS
      during the last month of pregnancy and first month postpartum did not correlate
      (p > 0.05) with milk yield or reproductive performance. Blood the metabolite
      profiles were not consistently related to productive or reproductive variables.
      The effect of farm and season was significant (p < 0.05) on most of the response
      variables and low productivity on overstocked farms lead to the conclusion that
      the low reproductive performance of DPC was linked to poor pasture management.
      During Phase II, farms A (FA) and D (FD) produce more milk than the others. Days
      to first service, days open, and calving interval were similar for farms B (FB)
      and C (FC), highest for Farm A, and lowest for Farm D. The forage availability
      mean was above the critical range of 6-8 kg of dry matter per 100 kg of
      liveweight (kg DM/100 kg LW) in all farms (range from 6.1 +/- 5.0 to 21.1 +/-
      11.2 kg DM/100 kg LW). Farm D had the highest stocking rate (1.5 cows/ha), a
      rapid rotation (10 paddocks), a good forage availability (7.1 +/- 3.9 kg DM/100
      kg LW) with a good quality for a tropical pasture (11.6 +/- 2.4% crude protein),
      and an economic energy supplementation. These results suggest this type of
      management could be more widely employed to improve the productivity of DPC on
      smallholder farms in the Mexican tropics.

PMID- 10081792
TI  - Use of metabolic profiles in dairy cattle in tropical and subtropical countries
      on smallholder dairy farms.
AB  - Metabolic profile testing has generally been used as part of a multidisciplinary
      approach for dairy herds in temperate climates. Our goal was to evaluate the
      effectiveness of the technique for identifying constraints on productivity in
      small herds in environments less favorable for milk production. Metabolites
      tested were chosen for stability in the sample after collection of blood, ease of
      analysis and practical knowledge of the meaning of the results. Blood levels of
      five different metabolites in low-producing dairy cows belonging to smallholders
      in tropical and subtropical environments were measured. The study involved 13
      projects with 80 cows in each, carried out in six Latin American, six Asian, and
      one southern European countries. Data were also collected on feeding, body
      condition score (BCS) and weight change, parasitism, and reproduction. In Chile,
      Mexico, Paraguay, Philippines, Uruguay, and Venezuela, globulin levels were high
      in > 17% of cows sampled on each occasion. Globulin levels were also high in
      Turkey and Vietnam on one or more occasions. In Paraguay, 49% of cows had high
      globulin levels at two to three months after calving. These results suggest that
      inflammatory disease was present to a potentially important degree, although this
      was not always investigated and not always taken into account. In all countries
      except Mexico and Venezuela, high beta-hydroxybutyrate (BHB) levels before
      calving in many cows highlighted the presence of condition loss in late
      pregnancy, an important potential constraint on productivity and fertility. Fewer
      cows showed high BHB levels in lactation, whereas change in BCS and weight was
      more sensitive for measuring negative energy balance. Urea concentrations were
      low in only small numbers of cows suggesting that dietary protein shortages were
      not common. Albumin values were low mainly in cows where globulin values were
      high and, hence, did not generally provide additional information. The exception
      was in China where pregnant yaks over winter had high BHB and low albumin values,
      suggesting that they were seriously underfed. This observation stimulated a
      successful nutritional intervention in the following winter. Inorganic phosphate
      values were within the reference range in most countries a majority of the time
      suggesting, contrary to expectation, that this mineral was not commonly a
      constraint. The use of metabolic profile testing proved valuable in drawing
      attention to important potential constraints on productivity in dairy cows in
      tropical and subtropical environments and in confirming those which were not.

PMID- 10081793
TI  - Blood metabolites and their relationship with production variables in dual
      purpose cows in Venezuela.
AB  - A survey was carried out on 79 lactating Bos taurus/indicus cross-bred cows on
      three dual-purpose cattle farms to measure the blood concentration of metabolites
      and to evaluate possible relationships with nutritional status and productive
      variables. A rotational grazing system on Star grass and other tropical pastures
      (10-12% CP in leaves) was used and 2-3 kg/cow/day of concentrate were fed on two
      farms. Restricted calf suckling was used in two herds. Average milk yield sold
      per farm was 6 kg/day/cow and body condition scores (BCS) were between 3.0 and
      3.8 on a scale of one-to-five. On two farms, the average interval from calving to
      conception (ICC) was more than 145 days. Mean blood concentrations of albumin,
      globulin, urea, beta-hydroxybutyrate and phosphorus were generally within
      reference values, but a significant group of cows had low levels of albumin and
      urea and high levels of globulin. Packed cell volume (PCV) was below normal
      values, with anemia in 63% of cows during the second trimester of lactation,
      which was negatively correlated to milk yield. The high incidence of anemia could
      be related to factors such as hematophagic parasites, not evaluated in this
      study. ICC values were negatively related to albumin level and could be
      associated with protein deficiency in the diet or with disease, as globulin
      values were high in many cows. Based on these diagnoses, an experiment was
      carried out on one of the farms to evaluate the influence of supplementation with
      0.5 kg/cow/day of fish meal. Total milk yield was not influenced by the fish meal
      and reproductive efficiency was high in the two supplemental treatments. It was
      shown that supplementation with undergraded protein is not required in these
      cows.

PMID- 10081794
TI  - Enhancing the profitability of pasture-based dairy production in the humid
      tropics through improved nutrition.
AB  - Dairy production in the tropics represents a major challenge, especially when
      reliant on grazed forages, because of the conflicting factors of a high
      nutritional demand to sustain lactation on the one hand, and the relatively low
      quality of tropical grasses and a stressful environment, on the other. This paper
      focuses primarily on those tropical situations where grazed pasture is the
      cheapest feed resource. Effective management of the pasture as well as the
      animals that graze it is required in order to maximize economic viability of the
      farming enterprise. Feed planning helps to ensure that pasture use is maximized,
      either directly by grazing or, where profitable, indirectly by cutting for
      conservation. High rates of pasture utilization at each grazing minimize pasture
      senescence and decay and ensure that pasture remains in a vegetative state of the
      highest possible nutritional quality. Total annual feed requirements of the
      grazing herd must therefore be matched as closely as possible to the total annual
      pasture production on the farm. Stocking rate is critical in this regard, and is
      the single most important determinant of productivity in pastoral farming.
      Periods of pasture surplus or deficit will inevitably arise, but can be minimized
      by matching the monthly feed requirements of the herd as closely as possible to
      the monthly feed production on the farm. Herd requirements can be influenced, for
      example, through altering calving patterns and drying off dates. Even with good
      pasture management practices, it is highly likely that tropical pasture quality
      will be low for part of the year. Utilization of low-quality forages can be
      improved through the appropriate use of feed supplements, and the key principles
      are discussed. Firstly, conditions for optimum fermentative digestion in the
      rumen must be promoted through adequate provision of fermentable energy and
      nitrogen as well as essential minerals, such as phosphorus and sulfur. Further
      supplementation with metabolizable energy or protein, depending on what limits
      animal production, may be profitable. Various practical supplementation
      strategies for tropical forages are discussed. Finally, some suggestions for
      future research and development for enhancing the profitability of pasture-based
      dairy production in the humid tropics are made.

PMID- 10081795
TI  - Bulk milk urea concentrations and their relationship with cow fertility in
      grazing dairy herds in southern Chile.
AB  - Milk urea determination is being used as a broad indicator of protein/energy
      imbalance in dairy herds. The main purpose of this study was to compare blood and
      bulk milk urea values in grazing herds, to evaluate their seasonal variation
      under South Chilean conditions, and to examine their potential relationships with
      herd fertility. The association between herd blood urea concentration (mean of
      seven lactating cows) and bulk milk urea concentration (tank containing milk from
      the previous 24 h) was determined in 21 diary herds. Reference values, seasonal
      and herd variance, and the frequency of herds with values outside a range of 2.5
      to 7.3 mmol/l were determined in bulk milk samples obtained monthly for a period
      of one year from 82 suppliers at two creameries located in southern Chile.
      Finally, bulk milk urea was measured every two weeks in samples from 24 herds,
      and the first service conception rate (FSCR) from 2153 dairy cows was determined.
      Mean bulk urea concentration was highly correlated with mean herd blood urea
      concentration (r = 0.95; p < 0.01). Mean urea concentration in the bulk milk
      samples obtained during one year from 82 herds was 4.9 +/- 1.2 mmol/l, with a
      range of 1.5 to 11.6 mmol/l. The highest values were found during spring and the
      lowest values during the summer. There was a high seasonal variation (CV = 13
      47%) and between-herd variation (CV = 20-31%). Out of a total of 984 samples,
      5.4% had urea values > 7.3 mmol/l and 3.8% had values < 2.5 mmol/l. Of the 82
      herds, 27% had values outside the reference interval (2.5-7.3 mmol/l) on two or
      more occasions. FSCR was lower in herds when the bulk milk urea was > 7.3 mmol/l
      (50.7%) than in cows, where the urea concentration was < 5.0 mmol/l (73.8%) at
      the time of insemination. The study concluded that bulk milk urea concentrations
      provided information similar to herd blood urea concentrations in local grazing
      dairy herds. There was a high frequency of herds with abnormal values, with large
      variations between herds and between seasons. Increased milk urea concentrations
      during spring were associated with lower conception rates.

PMID- 10081796
TI  - Constraints on dairy cattle productivity at the smallholder level in the
      Philippines.
AB  - Survey data on dairy cattle production were gathered in two sites [Site I (three
      year survey) and Site II (two-year survey)] in Southern Luzon, Philippines.
      Crossbred (Holstein-Friesian x Sahiwal) dairy cows (n = 122) managed by
      smallholder farmers belonging to five primary cooperatives under the federation
      of dairy farmers, were monitored monthly for milk production, feed intake and
      availability, and reproduction and health status. The purpose of the survey was
      to identify constraints to productivity. The reproductive status of the cows was
      monitored by measuring milk and plasma progesterone concentrations by
      radioimmunoassay and rectal palpation of the ovaries. Plasma concentrations of
      selected metabolites [beta-hydroxybutyrate (BHB), inorganic phosphorus, albumin,
      globulin, urea] were also measured at one month before calving and at one month
      and 2-3 months postpartum, to determine if these could serve as biochemical
      indicators of nutritional stress. A long calving interval (CI = > 400 days) was
      identified as the major constraint to productivity of dairy cattle on smallholder
      farms. The three main problems related to this reproductive constraint were: (1)
      poor breeding management, in particular lack of accurate estrus detection; (2)
      repeat breeding, i.e. three or more services were required before conception; and
      (3) poor ovarian function, shown by some cows with lose progesterone levels. An
      important cause of these problems was undernutrition, particularly at critical
      periods of the cow's reproductive life, reflected in the slow recovery from loss
      in body weight and condition score during the early postpartum period and the
      increased plasma BHB values at peripartum period in some cows, indicative of
      negative energy balance, and the flat lactation profile. These findings are
      useful and relevant as a database in the development of an appropriate management
      scheme aimed toward improving dairy cattle production and productivity at
      smallholder level. It highlights the importance of estrus detection, good
      breeding management and the use of a practical strategic nutritional
      supplementation, particularly during stressful periods in the cows's reproductive
      life.

PMID- 10081797
TI  - Supplement strategies for ruminants and management of feeding to maximize
      utilization of roughages.
AB  - Principles of supplementation are discussed in respect of both, their positive
      and negative effects on roughage digestion and utilization by ruminants. It is
      pointed out that negative effects mainly occur when excessively processed
      concentrate is given in large quantities two times per day. This lowers rumen pH
      which in turn depresses cellulose digestion and intake of cellulosic feeds,
      leading to problems of acidosis and secondary ketosis due to off-feed conditions.
      To a large extent, such problems can be overcome by limited processing and
      feeding the concentrate mixed with the roughage. Supplements can also have
      positive effects by alleviating deficiencies such as nitrogen or by providing
      easily fermentable fiber to increase microbes for attachment to roughages.
      Supplements can increase microbial protein production and undegraded protein
      supply. It is emphasized that proper use and management of supplements can make
      the difference between profit and loss for small farmers.

PMID- 10081798
TI  - Use of urea-molasses-multinutrient block and urea-treated rice straw for
      improving dairy cattle productivity in Vietnam.
AB  - After conducting a preliminary survey, a feeding trial was carried out to
      determine the effect of urea-molasses-multinutrient block (UMMB) and urea-treated
      rice straw (UTRS) as a feed supplement on the productivity of dairy cows. Sixty
      Holstein-Friesian crossbred cows on 11 smallholder farms were divided equally
      into control, UMMB and UTRS supplementation groups. Milk yield and feed intake
      were recorded daily. Milk fat content, body weight and body condition score (BSC)
      of each cow were determined at two week intervals. Milk samples for progesterone
      analysis were collected once a week commencing one month after parturition. Data
      were recorded for date of onset of ovarian activity, estrus, insemination, and
      conception rate. Milk production increased by 10.3-11.9% and milk fat content
      increased by 3-5%, therefore, profit for farmers increased by US $0.55-0.73 per
      cow per day (exchange rate US $1 = VN $11,000). The intervals from calving to
      onset of ovarian activity (91-94 days), to estrus (110-114 days), to conception
      (121-122 days) and the calving interval (13.4-13.6 months) in the trial groups
      were significantly shorter than those in the control group (112, 135, 152 days
      and 14.4 months, respectively.

PMID- 10081799
TI  - Effect of strategic feed supplementation on productive and reproductive
      performance in yak cows.
AB  - A total of 2230 yak cows (5-13 years of age) in two populations with different
      milking systems were investigated. One population had a system of milking once a
      day (MOD), and the other population twice a day (MTD). The average milk yield of
      MOD cows was 0.7 +/- 0.2 kg/day within a milking period of 109 +/- 9 days. This
      compared with an average of 1.24 +/- 0.3 kg/day in 127 +/- 6 days in MTD yaks (p
      < 0.01). The cows showed a calving rate of 71% under the MOD system and 51.4%
      under the MTD system. Three farms with a total of 104 MTD cows between six and 12
      years of age were used to provide three different feeding groups. The groups were
      fed with, or without oat hay or highland barley straw in amounts of 1-1.5
      kg/head/day from December to April. The three farms were designated as Farm I,
      Farm II, and Farm III. Farm I had 41 cows with body weight of 230 +/- 67 kg each
      for grazing with no supplement (GNS). Farm II had 30 animals with body weight of
      216 +/- 28 kg each for grazing + oat hay (GOH). Farm III had 33 animals body
      weight of 221 +/- 34 kg each for grazing + highland barely straw (GBS). The
      calving rates of the cows in GOH and GBS were 23 and 19% higher, respectively,
      than GNS cows (p < 0.01), and the highest rate reached 76.7% in GOH. The live
      weight loss of the cows in GNS was considerably higher (p < 0.01) than in the two
      other groups. Ten GOH cows and 12 GNS cows were used to collect milk samples for
      measuring the progesterone concentration using RIA kits provided by IAEA/FAO:
      Milk was sampled every five days from calving until 90 days postpartum. In the
      unsupplemented group, milk progesterone (P4) levels suggested that cows had
      started cyclic ovarian activity by 40 days postpartum, whereas only 25% had been
      observed in estrus. In the supplemented group, 80% of cows had started cyclic
      ovarian activity by the same time and 70% had been seen in estrus. Two types of
      cyclic activity in terms of progesterone changed were found. With Type I
      (normal), 50 and 80% of cows from GNS and GOH, respectively, had cyclic changes
      of P4 in milk at 40 days postpartum. With Type II, the P4 levels in the milk
      remained 0.89 ng/ml until 90 days postpartum. A total of 46 grazing cows between
      five and 13 years of age (body weight 214 +/- 68 kg) was used to collect blood
      samples to measure concentrations of nutrient of metabolites at two weeks pre
      calving and at two weeks, two months and four months postcalving, respectively.
      The concentrations of nutrient metabolites [albumin, globulin, urea, beta
      hydroxybutyrate (BHB) and inorganic phosphorus] suggested general underfeeding of
      energy and protein in the winter/late pregnancy period with some recovery in
      lactation. Energy constraints appeared again as the summer progressed. No dietary
      phosphate deficiency was found. BHB and albumin testing on serum yaks could be a
      useful tool to identify poor nutritional status during the winter and so
      illustrate the need for supplementation.

PMID- 10081800
TI  - Effects of winter supplementation and antiparasite treatment on the productive
      performance of milk herd in the central-south region of Chile.
AB  - During the winter of 1994, a survey of productive and reproductive parameters was
      undertaken in the south-central part of Chile (8th Region) on 71 cows provided by
      four small farms with low production (< 3000 l/year). A low food intake was
      recorded (8.6 +/- 0.2-12.4 +/- 0.2 kg DM/day) and, as a result, the cows calved
      with poor body condition score (1.9 +/- 0.04 points on the scale of one-to-five,
      had milk production between 10.5 +/- 0.4 and 12.8 +/- 0.6 l/day, had a delayed
      start of ovulatory activity (78.2 +/- 4.6 days) and an interval between calving
      and conception of 120.3 +/- 4.6 days. In addition, low levels of packed cell
      volume (PCV) and hemoglobin (HEM) were found, which were considered to be a
      combined effect of low feed ingestion and parastic infection by Fasciola
      hepatica. To improve the productive and reproductive parameters, treatments were
      undertaken in three of the four small farms; a parasiticide treatment was used
      against the F. hepatica at the beginning of the winter and the availability of
      forage was increased via the use of supplementary green oats. Spring crops were
      also cultivated: corn for silage and oats with peas to make hay. The antiparasite
      treatment and supplementation of forage was associated with better body condition
      score at calving, improved hematological parameters, increased milk production
      (17%), reduced number of days to conception (120 vs. 91) and increased conception
      rate at first service (36 vs. 60%). In the fourth small farm where no
      interventions were undertaken, the parameters obtained during 1994 remained
      unchanged.

PMID- 10081801
TI  - Constraints to milk production in grazing dairy cows in Brazil and management
      strategies for improving their productivity.
AB  - Productivity in most Brazilian dairy herds is low and depends exclusively on
      pasture. To study the productive potential of pastures and to devise strategies
      to further improve pasture and animal productivity in this production system,
      studies were carried out to obtain basic on-farm information. The constraints
      which affect productivity and reproductive performance of dairy cows, the effects
      of restrictions in suckling time of calves, and strategic supplementation during
      the dry season upon animal production were the evaluated parameters. From March
      1992 through February 1997, studies were carried out on four private farms in the
      northern region of the State of Sao Paulo. Between March 1992 and February 1994
      (Study 1--survey phase), 142 cows (parity = 1-6) grazed pasture which consisted
      of signal grass (Brachiaria decumbens and Brachiaria brizanta). Once-a-month data
      were collected on body weight, body condition, and milk production. Reproduction
      parameters were assessed by milk progesterone profiles. From March 1996 to
      February 1997 (Study 2--intervention phase), 45 lactating dairy cows from two
      farms were hand-milked once a day and the calf suckling was restricted to two
      hours after milking. Data were collected on milk production and cow body weight.
      In Study 1, cows were grouped by calving date for the analysis of the
      reproductive and production data. Concentrations of blood metabolites,
      hemoglobin, and hematocrit were compared among randomly selected cows (n = 69)
      from all farms. Estimated pasture available per hectare (ha) at any time, crude
      protein (CP), and dry matter digestibility (DMD) of pasture available for grazing
      differed (p < 0.05) between seasons [pasture available = 1.2, 1.4, 1.8 and 2.2
      t/ha (SE = 0.70); CP = 42, 60, 48 and 57 g/kg (DM) (SE = 10.1); DMD = 399, 468,
      401 and 457 g/kg (DM) (SE = 21), respectively, for dry season 1992 (D92), wet
      season 1992 (W92), dry season 1993 (D93), and wet season 1993 (W93)]. The
      proportion of animals showing ovarian activity at 90 days postpartum (DPP) was
      higher for cows which calved in the wet season than cows which calved in the dry
      season. In Study 2, milk production tended to the higher (7.3 and 6.5 kg/day,
      respectively, for the intervention and survey studies; p = 0.08). The data
      suggest that milk production is being limited by pasture availability, the
      quality of pasture, and the lack of supplementation. We suggest that, although
      supplementing cows in the dry period may have an economic advantage, better
      pasture management needs to be introduced. Stocking rate must be adapted to
      pasture productivity and pasture quality throughout the year.

PMID- 10081802
TI  - Influence of farm, feed-producer and season on incidence of gastrointestinal
      disorders in Danish farm mink.
AB  - The distribution of gastrointestinal disorders in mink in Danish farms is
      presented based on data collected in a longitudinal design. The time at risk was
      from weaning in June until pelting in November. The occurrence of
      gastrointestinal disorders after weaning of the mink kits together with the
      distribution within farms was studied. The period of highest risk was in the
      months immediately after weaning (July and August). More than 17% of the farms
      recorded GI disorders among > or = 10% of pairs of animals. A multilevel
      statistical analysis showed that besides the effect of time after weaning, a
      significant part of the variation in the incidence could be attributed to the
      farm and feed-producer. The potential for bias is discussed.

PMID- 10081803
TI  - Attitudes of Finnish veterinarians about programs to control canine genetic
      diseases.
AB  - A mailed questionnaire survey was performed amongst the members of the Finnish
      Veterinary Association in order to study veterinarians' knowledge of canine
      inherited diseases and the present screening and control programs in Finland. The
      purpose was also to study the veterinarians' attitudes about and compliance with
      such programs. Veterinarians estimated that their knowledge is quite poor--but
      they believed in their ability to influence other groups and to promote the
      programs. The present programs were considered to have a positive effect on the
      prevention of canine inherited diseases--but information directed to
      veterinarians and other key groups could give even better results. Inherited
      skeletal diseases were thought to be important to canine well-being; the
      importance of inherited ocular diseases was assessed to be lower.

PMID- 10081804
TI  - A quantitative assessment of the validity of animal-health surveys using
      stochastic modelling.
AB  - This paper presents a stochastic simulation model to evaluate the efficacy of
      regional or national surveys aimed at identifying infection in populations of
      animals. The process of evaluation involves specification or calculation of
      cluster-level test sensitivity and specificity, which are derived from two
      probability distributions of the number of individual-level positive tests
      expected from non-infected and infected clusters, respectively. Probability
      distributions for the number of positive clusters expected in a situation of
      freedom from infection and under various levels of cluster prevalence are
      specified and used to determine survey properties (the survey being considered a
      diagnostic system), and ROC curves are drawn. Likelihood ratios allow
      investigators to state the extent to which a survey result is more likely to be
      observed if the region or country is infected at a given prevalence than if it is
      free from infection. The result of a survey carried out to investigate the
      presence of porcine reproductive and respiratory syndrome (PRRS) in Switzerland
      is used to illustrate this approach. The model can be adapted to a wide range of
      survey designs.

PMID- 10081805
TI  - A survey of Newcastle disease in Swiss laying-hen flocks using serological
      testing and simulation modelling.
AB  - Newcastle disease (ND) is a highly contagious viral disease of birds particularly
      domestic poultry. Switzerland is currently declared free from ND; since
      vaccination is prohibited, the detection of antibodies against ND virus (NDV)
      results in the destruction of the respective flock (stamping-out policy).
      However, in 1995 and 1996, antibody-positive flocks were detected and sporadic ND
      outbreaks even occurred in Switzerland. Therefore, a serosurvey was done to look
      for evidence of NDV infections in Swiss laying-hen flocks. The survey was
      designed to provide 95% confidence of detecting at least one seropositive flock
      if the flock prevalence were 1%. Thirty blood samples from each of 260 commercial
      laying-hen flocks were collected during 1996 in a central poultry slaughterhouse.
      Sera were screened for NDV antibodies with a commercial blocking enzyme-linked
      immunosorbent assay (ELISA). Samples with a questionable or positive test result
      were retested with the same ELISA. A stochastic computer model was applied to
      define a cut-off number of test-positive samples to help to differentiate between
      true- and false-positive flocks and to estimate the true flock prevalence of
      infection. Four flocks were identified as NDV-seropositive and the NDV true
      seroprevalence among commercial laying-hen flocks in Switzerland was most likely
      between 1.35 and 1.55%. This indicates that Swiss laying-hen and parental flocks
      with more than 150 animals have been in contact with strains of NDV that cause
      subclinical infection in chicken, because no clinical symptoms have been
      observed. In this context, computer simulation was a useful technique to
      interpret survey results.

PMID- 10081806
TI  - Prevalence of Surra among camels and horses in Jordan.
AB  - The prevalence of Trypanosoma evansi infection among camels and horses in Jordan
      was studied using thick blood smears and inoculation techniques with mice and
      rats. A total of 437 camels and 83 horses from four climatic zones were surveyed.
      In addition, 40 donkeys, 32 cattle and 35 goats in contact with infected camels
      and horses were also tested in the same way. Clinical disease was evident in 8.2%
      of the camels (36 out of 437) and in 9.6% of the horses (8 out of 83). Infection
      was limited only to the Sweama area on the Dead Sea (within the warm desert
      climatic zone), with prevalence of 30.5% and 33.3%, respectively, for camels and
      horses. Donkeys, cattle and goats examined were all free from T. evansi.
      Clinically affected camels were positive by both, thick blood smear and mouse and
      rat inoculations. Rat and mouse inoculations revealed (X2 = 3.2, df = 1, exact p
      = 0.07) greater number of positive cases in horses than those revealed by thick
      blood smears. T. evansi-infected camels and horses showed all the clinical signs
      known for Surra. In addition, it was observed that 100% of infected camels stared
      at the sun.

PMID- 10081807
TI  - [Capnocytophaga canimorsus infections: a possibly fatal complication of bite
      wounds].
AB  - Practising veterinarians and their assistants run the risk of being bitten by
      their patients, mostly cats and dogs, and many have experienced that bites and
      bite-wound infections can have unpleasant consequences. In recent years, more
      insight has been gained into a 'new' bacterial infection of bite wounds that not
      only has severe local effects but also potentially fatal systemic consequences.
      The bacterium involved is Capnocytophaga canimorsus. All bite wounds should be
      treated adequately, but this is especially so when wounds are infected with C.
      canimorsus. In this article, dog and cat bites are briefly described and then an
      overview is given of current knowledge of C. canimorsus and appropriate
      prophylactic measures.

PMID- 10081808
TI  - [Risk increase and economic consequences of the introduction of contagious animal
      diseases in the Netherlands].
AB  - The paper describes the development of the Monte Carlo simulation model VIRiS
      (Virus Introduction Risk Simulation) and the results obtained with this model.
      VIRiS simulates the introduction of Classical Swine Fever (CSF) and Foot and
      Mouth Disease (FMD) into the Netherlands. The model is based on objective
      information (research, databases), complemented by expert knowledge. Various
      questionnaire techniques (Conjoint Analysis, ELI) were used in order to elicit
      the experts' estimates in an objective and quantitative way. VIRiS provides
      information on the number of primary outbreaks in a certain period, their
      geographic location, causative risk factor, and causative country (or region).
      The information provided by VIRiS in combination with the outcome of models
      describing the spread and economic consequences of epidemics provides a tool that
      can be used to evaluate prevention strategies for their ability to reduce annual
      losses due to outbreaks.

PMID- 10081809
TI  - [Results of an inquiry about the surgical order].

PMID- 10081810
TI  - [Perianal fistula].

PMID- 10081812
TI  - Parasitism, host immune function, and sexual selection.
AB  - Parasite-mediated sexual selection may arise as a consequence of 1) females
      avoiding mates with directly transmitted parasites, 2) females choosing less
      parasitized males that provide parental care of superior quality, or 3) females
      choosing males with few parasites in order to obtain genes for parasite
      resistance in their offspring. Studies of specific host-parasite systems and
      comparative analyses have revealed both supportive and conflicting evidence for
      these hypotheses. A meta-analysis of the available evidence revealed a negative
      relationship between parasite load and the expression of male secondary sexual
      characters. Experimental studies yielded more strongly negative relationships
      than observations did, and the relationships were more strongly negative for
      ectoparasites than for endoparasites. There was no significant difference in the
      magnitude of the negative effect for species with and without male parental care,
      or between behavioral and morphological secondary sexual characters. There was a
      significant difference between studies based on host immune function and those
      based on parasite loads, with stronger effects for measures of immune function,
      suggesting that the many negative results from previous analyses of parasite
      mediated sexual selection may be explained because relatively benign parasites
      were studied. The multivariate analyses demonstrating strong effect sizes of
      immune function in relation to the expression of secondary sexual characters, and
      for species with male parental care as compared to those without, suggest that
      parasite resistance may be a general determinant of parasite-mediated sexual
      selection.

PMID- 10081813
TI  - Dispersal, gene flow, and population structure.
AB  - The accuracy of gene flow estimates is unknown in most natural populations
      because direct estimates of dispersal are often not possible. These estimates can
      be highly imprecise or even biased because population genetic structure reflects
      more than a simple balance between genetic drift and gene flow. Most of the
      models used to estimate gene flow also assume very simple patterns of movement.
      As a result, multiple interpretations of population structure involving
      contemporary gene flow, departures from equilibrium, and other factors are almost
      always possible. One way to isolate the relative contribution of gene flow to
      population genetic differentiation is to utilize comparative methods. Population
      genetic statistics such as FST, heterozygosity and Nei's D can be compared
      between species with differing dispersal abilities if these species are otherwise
      phylogenetically, geographically and demographically comparable. Accordingly, the
      available literature was searched for all groups that meet these criteria to
      determine whether broad conclusions regarding the relationships between
      dispersal, population genetic structure, and gene flow estimates are possible.
      Allozyme and mtDNA data were summarized for 27 animal groups in which dispersal
      differences can be characterized. In total, genetic data were obtained for 333
      species of vertebrates and invertebrates from terrestrial, freshwater and marine
      habitats. Across these groups, dispersal ability was consistently related to
      population structure, with a mean rank correlation of -0.72 between ranked
      dispersal ability and FST. Gene flow estimates derived from private alleles were
      also correlated with dispersal ability, but were less widely available. Direct
      count heterozygosity and average values of Nei's D showed moderate degrees of
      correlation with dispersal ability. Thus, despite regional, taxonomic and
      methodological differences among the groups of species surveyed, available data
      demonstrate that dispersal makes a measurable contribution to population genetic
      differentiation in the majority of animal species in nature, and that gene flow
      estimates are rarely so overwhelmed by population history, departures from
      equilibrium, or other microevolutionary forces as to be uninformative.

PMID- 10081814
TI  - Studies on arylfuran derivatives. Part VII. Synthesis and characterization of
      some Mannich bases carrying halophenylfuryl moieties as promising antibacterial
      agents.
AB  - A series of 4-[5-(halophenyl)-2-furfurylidene)] amino-3-mercapto-5-substituted
      1,2,4-triazoles (3) were synthesized. Aminomethylation of 3 with formaldehyde and
      a secondary amine furnished Mannich bases, 4. Both Schiff bases and Mannich bases
      were characterized on the basis of IR, NMR, mass spectral data and elemental
      analysis. All the newly synthesized compounds were tested for their antibacterial
      activities. Some of them carrying morpholino and N-methylpiperazino residues were
      found to be promising antibacterial agents.

PMID- 10081815
TI  - SAR studies on H2 antagonists containing alkylamino substituted 1,2, 5
      thiadiazole 1-oxide moieties.
AB  - A number of ranitidine analogues in which the diamino-1,2,5-thiadiazole 1-oxide
      substructure bearing alkyl chains of different length is present as the urea
      equivalent group, were synthesised and studied for their lipophilic and H2
      antagonist properties. Derivatives which displayed a logP < or = 3 behaved as
      competitive antagonists of histamine at H2 receptors present on guinea pig right
      atrium. The remaining more lipophilic members of the series showed an
      insurmountable antagonism not completely reversible after prolonged washing. A
      binding study suggested that an increase in the length of alkyl chain gave rise
      to hydrophobic interactions with the receptor which were responsible for the
      apparent irreversible H2 antagonism shown by the higher homologues of the series.

PMID- 10081816
TI  - Synthesis and antimicrobial activity of some 5-aryl-2-[N,N-disubstituted
      thiocarbamoylthio)acylamino]-1,3,4-oxadiazoles.
AB  - In this study, a number of novel 5-aryl-2-[(N,N-disubstituted
      thiocarbamoylthio)acylamino]-1,3,4-oxadiazole derivatives were synthesized by the
      reaction of potassium salts of N,N-disubstituted dithiocarbamoic acids with 2
      [(alpha-chloro-alpha-phenylacetyl/alpha-bromopropionyl)-amino]-5 -aryl-1, 3,4
      oxadiazoles. Structures of the compounds were confirmed by the spectral data (IR,
      1H NMR, EIMS) and elemental analyses. Most of the compounds were tested against
      various microorganisms and four of them were found to be weakly active against
      Staphylococcus aureus and Staphylococcus epidermidis.

PMID- 10081817
TI  - Toward the rational development of peptidomimetic analogs of the C-terminal
      endothelin hexapeptide: development of a theoretical model.
AB  - In an early report on the structure-activity relationship of endothelin (ET)
      peptides, it was reported that the C-terminal hexapeptide ET(16-21), His-Leu-Asp
      Ile-Ile-Trp, is the minimum ET fragment which maintains biological activity in
      some, but not all the tissues responding to ETs. Subsequently, other authors
      described a series of analogs of this peptide, in which the His 16 residue was
      replaced by non-natural amino acids, characterized by bulky aromatic side chains.
      Among them, two well-characterized non-selective ETA/ETB antagonists were PD
      142893 and PD 145065; interest in these potent ET antagonists was, however,
      reduced by their peptidic structure which was likely to lead to undesirable
      properties such as poor bioavailability and short duration of action. On the
      basis of these premises, our previous studies led to the development of a
      peptidomimetic ligand of ET receptors (compound 3), based on the replacement of
      the His 16 residue of ET(16-21) with an (E)-N-(benzyloxy)iminoacyl moiety;
      compound 3 proved to possess a certain affinity for ET receptors, albeit lower
      than that shown by PD 142893 and PD 145065. We report here on ETA/ETB binding
      affinity of compounds 4-12, designed as a new series of ET(16-21) analogs.
      Compounds 4 and 5 were practically devoid of any affinity; derivatives 6-12
      exhibited appreciable affinity indices for ETB receptors higher than that shown
      by 3, even if still lower than that obtained for PD 145065. This paper also
      describes the development of a pharmacophoric model able to explain the ET
      receptor binding properties of our hexapeptide analogs compared with those of PD
      142893 and PD 145065 and IRL2500, recently reported as a potent ETB selective
      endothelin antagonist.

PMID- 10081818
TI  - Synthesis and mu-opioid receptor affinity of a new series of nitro substituted
      3,8-diazabicyclo[3.2.1]octane derivatives.
AB  - A new series of analogues (1c-j; 2c-i) of the previously reported analgesic 3,8
      diazabicyclo[3.2.1]octanes (1a,b; 2a,b) was synthesized and tested for their
      affinity towards mu-opioid receptors. Modifications were introduced either at the
      cinnamyl or the acyl side chains. The majority of the new compounds, with the
      exception of 1c,j and 2c, showed Ki values better or comparable with those of the
      models.

PMID- 10081819
TI  - Synthesis and antituberculosis activity of some new 2-quinoxalinecarbonitriles.
AB  - Tuberculosis, an ancient disease undergoing recent control by public hygiene and
      drug therapy, has experienced a recrudescence throughout the world. New and
      effective therapies are rapidly needed to combat infections caused by these
      strains. Some new 2-quinoxalinecarbonitriles have been synthesized and tested as
      antituberculosis agents and interesting results have been obtained from the first
      screening.

PMID- 10081820
TI  - Studies on some N-bridged heterocycles derived from bis-[4-amino-5-mercapto-1,2,4
      triazol-3-yl] alkanes.
AB  - A series of bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl] alkanes have been
      synthesized and were converted into bis-[1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-4
      yl] alkanes. The newly synthesized compounds were characterized by analytical IR,
      NMR and mass spectral studies. Some of the newly synthesized compounds were
      screened for their antibacterial properties and exhibited activity with MIC in
      the range 3-12.5 micrograms/ml.

PMID- 10081821
TI  - Structure-activity relationship investigations of the modulating effect of core
      substituents on the affinity of pyrazoloquinolinone congeners for the
      benzodiazepine receptor.
AB  - A series of 6- and 7-substituted-2-arylpyrazolo[4,3-c]quinolin-3-ones was
      synthesized and tested in vitro for binding with the benzodiazepine receptor in
      competition with [3H]flunitrazepam. Electronic parameters (molecular
      electrostatic potential (MEP), charge distribution on the nitrogen atoms, dipole
      moment mu, and ionization potential (IP)) were calculated for the compounds by
      semi-empirical quantum chemistry methods. Lipophilicity of the compounds,
      expressed as logarithm of the octanol-water partition coefficient (log P), was
      calculated by the program Pallas. A quantitative correlation of the biological
      data with molecular parameters revealed a significant dependence (r = 0.95) of
      the activity on hydrophobic constants of the substituents, log P, and magnitude
      of the MEP minimum associated with the carbonyl oxygen atom.

PMID- 10081822
TI  - Preparation of new 5-aroylamino substituted 3-nicotinoyl/isonicotinoyl-1,3,4
      thiadiazol-2(3H)-ones with anti-inflammatory activity.
AB  - A series of 1,3,4-thiadiazol-2(3H)-ones (2a-j) with a nicotinoyl/isonicotinoyl
      group in position 3 and an aroylamino substituent in position 5 of the ring was
      prepared and evaluated for antipyretic and anti-inflammatory activities. All the
      title compounds and in particular 2e, 2i and 2j exhibited anti-inflammatory
      activity and were devoid of antipyretic properties.

PMID- 10081823
TI  - Synthesis and anti-inflammatory activity of esters derived from 5-aryl-1,2
      dihydro-2-(2-hydroxyethyl)-3H-1,2,4-triazole-3-thiones.
AB  - Some aliphatic and aromatic esters 2a-l were prepared starting from 5-aryl-1,2,4
      triazoline-3-thiones bearing a 2-hydroxyethyl chain in position 2. The title
      compounds were evaluated for antipyretic and anti-inflammatory activities. Nearly
      all derivatives and in particular 2f, 2h, 2k exhibited antiphlogistic properties
      but were lacking in antipyretic activity.

PMID- 10081824
TI  - Quinoxaline chemistry. Part 12. 3-Carboxy-2[phenoxy]-6(7)substituted quinoxalines
      and N-[4-(6(7) substituted-3-carboxyquinoxalin-2-yl)hydroxy] benzoylglutamates.
      Synthesis and evaluation of in vitro anticancer activity.
AB  - Thirty quinoxalines bearing a substituted phenoxy or hydroxybenzoylglutamate
      group on position 2, a carboethoxy or carboxy group on position 3 and a
      trifluoromethyl group on position 6 or 7 of the heterocycle were prepared in
      order to evaluate the in vitro anticancer activity. Screening over 21 compounds
      selected at the National Cancer Institute (Bethesda, MD) showed that only few
      derivatives exhibited a moderate growth inhibition activity on various tumor
      panel cell lines at 10(-4) molar concentration. The acid derivatives showed no
      growth inhibition activity. The results obtained in this series seem to indicate
      that in general carboxy or carboethoxy groups close to O-link with phenyl or
      benzoyl glutamates on position 2 are detrimental for anticancer activity.

PMID- 10081825
TI  - Synthesis of angelicin heteroanalogues: preliminary photobiological and
      pharmacological studies.
AB  - A series of angelicin heteroanalogues, in which the furan was replaced by
      thiophene or a 1-substituted pyrazole moiety, was synthesised in order to obtain
      potential therapeutic agents with antiproliferative and/or other biological
      activities. In general, the antiproliferative activity of the new thioangelicin,
      tested in different biological substrates, appeared to be higher than that of the
      angelicin, the natural parent compound, but lower than that of 8-MOP, the
      furocoumarin ordinarily used in PUVA therapy and photopheresis. Thioangelicin 6
      induced strong inhibition of T2 bacteriophage infectivity and was able to
      significantly repress the DNA synthesis in Ehrlich ascites cells and the clonal
      growth in HeLa cells. The pyrazolocoumarins did not show any noticeable effect
      upon UVA irradiation in all the biological systems considered. All the new
      angelicin heteroanalogues appeared to be free of the known phototoxicity of
      furocoumarins on the skin. The pyrazolocoumarins have also been tested as anti
      inflammatory, analgesic, antipyretic, local anaesthetic, anti-arrhythmic and
      platelet anti-aggregating agents by standard procedures. In this class of
      derivatives, 10a showed good anti-inflammatory and antipyretic properties, while
      9a and 11a showed significant local anaesthetic activity.

PMID- 10081826
TI  - A high-sensitive spectrofluorimetric method for the determination of micromolar
      concentrations of iron(III) in bovine liver with 4-hydroxyquinoline.
AB  - A new sensitive, rapid and accurate spectrofluorimetric method, suitable for the
      determination of micromolar concentrations of iron(III) in bovine liver, using 4
      hydroxyquinoline (4-HQ) in an alkaline medium (KOH 2.0 x 10(-2) mol/l) as
      fluorescent agent, is described. The fluorescence intensity of the working
      solutions was measured at lambda ex 305 nm and lambda em 380 nm. The observed
      decrease of the above mentioned intensity was mainly due to the quenching, caused
      by the interaction between the iron(III) to be analysed and the potentially
      fluorescent 4-HQ. The accuracy and the precision of the proposed method, after an
      experimental investigation, could be considered as very satisfactory. Potassium
      fluoride and triethylenetetramine solutions were successfully used for the
      masking of those metal cations existing in the bovine liver which interfere
      seriously with the determination of iron(III).

PMID- 10081827
TI  - Hydroxyamino sugar derivatives: sugar nitrones.
AB  - We describe in this paper the preparation of 46 new sugar nitrone derivatives and
      their antibacterial activity against Escherichia coli and Bacillus subtilis.

PMID- 10081828
TI  - Simultaneous determination of cysteine, cystine and 18 other amino acids in
      various matrices by high-performance liquid chromatography.
AB  - An extraction protocol and a reversed-phase high-performance liquid
      chromatographic method for the simultaneous determination of cysteine, cystine
      and 18 other amino acids in biological and vegetable samples are described. Among
      the different methods proposed for amino acid determination, phenylisothiocyanate
      was used as the reagent for derivatization. Chromatograms obtained in the
      analysis of standard solutions and actual samples are reported, together with
      regression equation, correlation coefficient (> 0.999 for all), limit of
      detection and recoveries (between 86 and 102% for all the examined matrices) for
      each amino acid. Practical protocol and method applications in normal patients
      and patients affected by different pathologies, and in algal products are
      discussed.

PMID- 10081829
TI  - Enrichment of low-copy-number gene products by hydrophobic interaction
      chromatography.
AB  - Enrichment of proteins in solution is the goal of a purification process and
      often a scientific challenge. We investigated the capacity of hydrophobic
      interaction chromatography to enrich proteins, potential candidates for novel
      drug targets. The soluble protein fraction of Haemophilus influenzae was
      fractionated over a TSK Phenyl column and the proteins resolved were analyzed by
      two-dimensional gel electrophoresis and matrix-assisted laser desorption
      ionization mass spectrometry. Approximately 150 proteins, bound to the column,
      were identified, 30 for the first time. Most of the proteins enriched by
      hydrophobic interaction chromatography were represented by major spots, so that
      an enrichment of low-copy-number gene products was only partially achieved. The
      proteins enriched by this chromatographic approach belong to various protein
      classes, including enzymes, ribosomal proteins and proteins with as yet unknown
      functions. The results include two-dimensional maps and a list of the proteins
      enriched by hydrophobic interaction chromatography.

PMID- 10081830
TI  - On-line solid-phase extraction liquid chromatography-continuous flow frit fast
      atom bombardment mass spectrometric and tandem mass spectrometric determination
      of hydrolysis products of nerve agents alkyl methylphosphonic acids by p
      bromophenacyl derivatization.
AB  - For proof of the presence of chemical warfare agents sarin, soman and VX, a
      rapid, accurate and sensitive method which allows us to determine their
      hydrolysis products ethyl methylphosphonic acid, isopropyl methylphosphonic acid
      and pinacolyl methyl phosphonic acid was explored by using continuous flow frit
      fast atom bombardment (FAB) LC-MS and LC-MS-MS. After derivatization of analytes
      with p-bromophenacyl bromide, LC-MS-MS analyses for screening were performed by a
      flow injection method. The three alkyl methylphosphonic acids (AMPAs) were eluted
      within 5 min, and the detection limits for the three AMPAs ranged from 1 to 5
      ng/ml. For confirmation of the screening results, LC-MS-MS analysis with
      chromatographic separation was conducted by using a narrow bore column. The three
      AMPAs were all eluted with excellent separation within 25 min, and the detection
      limits ranged from 1 to 20 ng/ml. Quantitative measurement was performed by LC-MS
      in selected ion monitoring (SIM) mode with chromatographic separation. Linear
      calibration curves were obtained for the three AMPAs and the detection limits
      ranged from 0.5 to 3 ng/ml. The relative standard deviation for peak area ranged
      from 3.4 to 6.0% at 50 ng/ml for the three AMPAs.

PMID- 10081831
TI  - Have you heard.

PMID- 10081832
TI  - Finding the comfort zone.

PMID- 10081833
TI  - Dangers at the dock.

PMID- 10081834
TI  - Fall protection. Certification arrives.

PMID- 10081835
TI  - Accelerating safe driving behavior.

PMID- 10081836
TI  - Toward safer needles.

PMID- 10081837
TI  - Safety awareness. Visible safety.

PMID- 10081838
TI  - Metabolic consequences of continent urinary diversion.
AB  - PURPOSE: Continent diversion, in particular orthotopic bladder substitution, is a
      well accepted form of urinary diversion. However, potential metabolic
      consequences in the early postoperative period as well as long term remain a
      serious problem. MATERIALS AND METHODS: We review the possible complications
      associated with removing bowel and incorporating it in the urinary tract.
      RESULTS: Metabolic complications following continent urinary diversion are
      common. In the majority of cases, and with correct patient selection and
      education, problems may be minimized with use of an appropriate bowel segment and
      early intervention. CONCLUSIONS: Careful patient selection and vigilant followup
      are essential for good long-term results in patients undergoing continent urinary
      diversion.

PMID- 10081839
TI  - Frere Jacques Beaulieu: from rogue lithotomist to nursery rhyme character.
AB  - PURPOSE: We discuss the history of Frere Jacques Beaulieu, a celebrated 17th
      century French lithotomist, and question the relationship of his name to a well
      known nursery rhyme character. MATERIALS AND METHODS: We reviewed historical
      reports about Beaulieu and his career as a lithotomist. Nursery rhyme
      interpretations were also reviewed. RESULTS: Beaulieu was born in 1651 to a
      peasant family and learned the practice of lithotomy by apprenticeship. He was
      never formally ordained yet donned a monk habit and called himself Frere Jacques.
      He was the first person to use the lateral approach to perineal lithotomy and
      openly shared his surgical technique. His lithotomy procedure was observed by the
      high court in Paris on 3 separate occasions between 1697 and 1704. Unfortunately
      his patients had significant morbidity and mortality, and he was denied operating
      privileges. He performed approximately 5,000 lithotomies in 30 years and died in
      1719 at age 68 years. The nursery rhyme "Frere Jacques" probably refers to a
      playful group of Jacobinic monks who often overslept. We found no direct
      association between Frere Jacques Beaulieu and the nursery rhyme character.
      CONCLUSIONS: Beaulieu was an early urologist who was the first to describe the
      lateral approach to perineal lithotomy. Unlike other lithotomists of the 17th
      century, he openly shared his surgical techniques and stimulated others to refine
      the procedure. Regardless of the exact derivation of the nursery rhyme, the name
      Frere Jacques will always be remembered in song.

PMID- 10081840
TI  - Detection of circulating prostate specific antigen expressing prostatic cells in
      the bone marrow of radical prostatectomy patients by sensitive reverse
      transcriptase polymerase chain reaction.
AB  - PURPOSE: The reverse transcriptase polymerase chain reaction (RT-PCR) assay for
      prostate specific antigen (PSA) expressing cells in the blood circulation has
      been under intense investigation since 1992. Although it has been suggested that
      this technology could be used as molecular staging for occult prostatic
      hematogenous metastases, we have been unable to confirm RT-PCR PSA positivity of
      peripheral blood to predict stage or recurrence in radical prostatectomy cases.
      We performed bone marrow RT-PCR PSA assay on a large cohort of radical
      prostatectomy cases and evaluate the use of this assay in improving prostate
      cancer staging and detecting early recurrence. MATERIALS AND METHODS: Unilateral
      anterior iliac crest bone marrow aspirates were performed on 116 patients
      immediately before radical prostatectomy between February 1995 and September
      1997. Radical prostatectomy specimens were processed as whole mounts. A sensitive
      nested RT-PCR assay with specific primers derived from the PSA sequence was used,
      which enabled us to detect PSA expressing LNCaP prostate cancer cells at the
      sensitivity of 1 cancer cell per 10 million lymphocytes (1/10(7)). A minimum of 3
      RT-PCR PSA reactions were performed on all patients and at least 2 positive tests
      were required to define positivity. Patients were followed for PSA recurrence
      (mean followup 14.7 months). RESULTS: PSA expressing cells were detected in bone
      marrow of 51 of 116 patients (44.0%) when at least 2 of 3 RT-PCR PSA assays per
      patient were positive. A much higher rate of RT-PCR PSA positivity was noted
      (77/116 patients, 66.3%) when any RT-PCR PSA positivity was considered. In 10
      randomly selected cases the RT-PCR product was confirmed as PSA by
      deoxyribonucleic acid sequencing. Of 51 bone marrow RT-PCR positive cases 25
      (49%) had organ confined disease and 26 (51%) had nonorgan confined disease.
      Similarly, bone marrow RT-PCR PSA was not associated with age, race, grade,
      pretreatment PSA or prostatic acid phosphatase value, clinical stage or margin
      status. However, the 2-year disease-free survival was 96.6% in RT-PCR negative
      patients versus 77.5% in RT-PCR positive patients (p = 0.054), and bone marrow RT
      PCR PSA was an independent prognostic factor in multivariate analysis including
      PSA, Gleason grade and pathological stage. CONCLUSIONS: Bone marrow RT-PCR PSA
      positivity in this study did not predict pathological stage, grade or margin
      positivity as determined from whole mount prostate cancer specimens. Furthermore,
      no relationship with age, grade or serum markers and bone marrow RT-PCR PSA
      positivity was noted. However, bone marrow RT-PCR PSA was associated with early
      disease recurrence. Further studies and longer followup are warranted to define
      the metastatic potential of the PSA expressing cells in the bone marrow of
      prostate cancer patients.

PMID- 10081841
TI  - Divergence between stone composition and urine supersaturation: clinical and
      laboratory implications.
AB  - PURPOSE: In general high urine supersaturation with respect to calcium oxalate,
      calcium phosphate or uric acid is associated with that phase in stones. We
      explore the exceptions when supersaturation is high and a corresponding solid
      phase is absent (type 1), and when the solid phase is present but supersaturation
      is absent or low (type 2). MATERIALS AND METHODS: Urine supersaturation values
      for calcium oxalate, calcium phosphate and uric acid, and other accepted stone
      risk factors were measured in 538 patients at a research clinic and 178 at stone
      prevention sites in a network served by a single laboratory. RESULTS: Of the
      patients 14% lacked high supersaturation for the main stone constituent (type 2
      structural divergence) because of high urine volume and low calcium excretion,
      perhaps from changes in diet and fluid intake prompted by stones. Higher calcium
      excretion and low urine volume caused type 1 divergences, which posed no clinical
      concern. CONCLUSIONS: Type 1 divergence appears to represent a condition of low
      urine volume which raises supersaturation in general. Almost all of these
      patients are calcium oxalate stone formers with the expected high supersaturation
      with calcium oxalate as well as high uric acid and calcium phosphate
      supersaturations without either phase in stones. Type 2 divergence appears to
      represent an increase in urine volume and decrease in urine calcium excretion
      between stone formation and urine testing.

PMID- 10081842
TI  - Frequency of urolithiasis in individuals seropositive for human immunodeficiency
      virus treated with indinavir is higher than previously assumed.
AB  - PURPOSE: Indinavir was approved by the Food and Drug Administration in 1996 as a
      human immunodeficiency type 1 protease inhibitor to treat human immunodeficiency
      virus infection. Prompted by the high number of patients receiving indinavir who
      present with renal colic at our institution, we performed a detailed
      investigation of the true frequency of urolithiasis during indinavir treatment.
      MATERIALS AND METHODS: We evaluated 105 patients with a mean age of 38.1 years
      who were treated with indinavir from 1996 to 1997. Before indinavir treatment was
      initiated all patients underwent renal ultrasonography, urinalysis, and
      determination of serum sodium, potassium, calcium, uric acid and creatinine. It
      was recommended that all patients drink 2 l of fluids daily, and all remained
      under continuous surveillance. RESULTS: Metabolic evaluation and ultrasonography
      showed no abnormality in any case. A stone episode occurred in 13 men (12.4%) as
      renal colic during observation. Colic recurred in 1 patient after 2 and 5 months,
      and in 1 after 2 months. Median duration of indinavir treatment until an acute
      stone episode was 21.5 weeks (range 6 to 50). A total of 12 stones passed
      spontaneously. Three patients underwent ureteroscopic calculous removal and 1 was
      treated with extracorporeal shock wave lithotripsy. CONCLUSIONS: Despite adequate
      patient information and compliance the rate of nephrolithiasis during indinavir
      therapy was 12.4%.

PMID- 10081843
TI  - Imaging characteristics of indinavir calculi.
AB  - PURPOSE: Indinavir sulfate is an effective protease inhibitor of the human
      immunodeficiency virus type 1. Use is associated with a significant incidence of
      crystallization and stone formation in the urinary tract, and these calculi are
      not visible on plain radiographs. Previously all urinary stones, including uric
      acid and matrix, were believed to be radiodense on computerized tomography (CT).
      We conducted a retrospective study to evaluate the radiographic appearance of
      indinavir calculi. MATERIALS AND METHODS: Retrospective chart review of 36
      patients taking indinavir sulfate and presenting with renal colic was performed
      with attention to presentation, urinalysis, radiographic evaluation and
      management. Specifically, imaging characteristics on CT were addressed. RESULTS:
      All patients complained of ipsilateral flank pain and 35 had nausea and/or
      vomiting. Of 30 patients with dysuria or urgency the majority had hematuria, and
      most had pyuria and/or proteinuria. No stones were visualized on abdominal
      radiography. Diagnosis was confirmed on 1 of 13 excretory urograms and 4 of 11
      renal ultrasounds. None of 12 CT scans was diagnostic of renal lithiasis.
      CONCLUSIONS: Indinavir sulfate is a protease inhibitor with poor solubility and
      significant urinary excretion. Crystallization and stone formation are
      demonstrated in as many as 20% of patients taking the medication. Most patients
      present with flank pain, nausea or vomiting and hematuria. Previously CT was
      thought to identify all urinary calculi with clarity but it cannot reliably
      confirm the presence of indinavir calculi.

PMID- 10081844
TI  - Single shot intraoperative excretory urography for the immediate evaluation of
      renal trauma.
AB  - PURPOSE: We reviewed the quality and usefulness of single shot intraoperative
      excretory urography (IVP) for evaluating suspected upper urinary tract trauma at
      our trauma center. MATERIALS AND METHODS: Between 1990 and 1997 single shot
      intraoperative IVP for staging renal injuries was performed in 50 patients in
      whom clinical instability and/or major associated injuries mandated an
      intraoperative study. Contrast material (2 ml/kg) was injected intravenously and
      images were obtained after 10 minutes. The quality and usefulness of each study
      were scored by a single attending urologist on a scale of 1-worst to 5-best.
      RESULTS: Intraoperative study quality was generally good (average score 3.84).
      The information obtained was generally considered useful for determining
      urological treatment (average score 3.96). In 16 patients (32%) intraoperative
      IVP findings safely obviated renal exploration. No contrast medium reactions were
      noted and no complications developed that were attributable to intraoperative
      IVP. CONCLUSIONS: Intraoperative single shot, high dose IVP is safe, efficient
      and of high quality in the majority of cases when performed as recommended. This
      study often provides important information that facilitates rapid and accurate
      decision-making. Intraoperative IVP is a useful tool for guiding the exploration
      of penetrating renal injuries and confirming blunt renal injuries that may be
      safely observed.

PMID- 10081845
TI  - Atheroembolic renal disease: effect on morbidity and survival after
      revascularization for atherosclerotic renal artery stenosis.
AB  - PURPOSE: Atheroembolic renal disease is increasingly found in older patients with
      general atherosclerosis. We evaluated the impact of atheroembolic renal disease
      on morbidity and survival after surgical revascularization for atherosclerotic
      renal artery stenosis. MATERIALS AND METHODS: The study group comprised 44
      patients who underwent surgical revascularization for atherosclerotic renal
      artery stenosis and concomitant intraoperative renal biopsy. Renal biopsy
      specimens were reviewed by a pathologist and evaluated for the presence or
      absence of atheroemboli, and the presence and severity of arteriolar
      nephrosclerosis. Postoperative patient data were reviewed to evaluate survival,
      and the incidence of renal and systemic morbid events. Patients were followed for
      1 to 14.5 years (median 6.2) after surgical revascularization. RESULTS:
      Atheroembolic renal disease was identified in the intraoperative biopsy specimen
      in 16 patients (36%, group 1) and was absent in 28 (64%, group 2), termed groups
      1 and 2. Atheroembolic renal disease correlated significantly with decreased
      patient survival. The 5-year survival in groups 1 and 2 was 54 and 85%,
      respectively (p = 0.011). Similarly the incidence of systemic atherosclerotic
      complications was significantly higher in group 1 than group 2 (86 versus 58%, p
      <0.05). In addition, renal or renovascular complications developed in more group
      1 than group 2 patients (p = 0.07). There was no significant association between
      the presence or severity of arteriolar nephrosclerosis and postoperative survival
      or morbid events. CONCLUSIONS: Our results indicate that atheroembolic renal
      disease is associated with decreased survival and an increased incidence of
      atherosclerotic morbid events after surgical revascularization for
      atherosclerotic renal artery stenosis. This information may be useful for
      therapeutic decision making in patients with atherosclerotic renal artery
      stenosis.

PMID- 10081846
TI  - 3-dimensional volume rendered computerized tomography for preoperative evaluation
      and intraoperative treatment of patients undergoing nephron sparing surgery.
AB  - PURPOSE: Computerized tomography (CT) is the diagnostic and staging modality of
      choice for renal neoplasms. Existing imaging modalities are limited by a 2
      dimensional (D) format. Recent advances in computer technology now allow the
      production of high quality 3-D images from helical CT. Nephron sparing surgery
      requires a detailed understanding of renal anatomy. Preoperative evaluation must
      delineate the relationship of the tumor to adjacent normal structures and
      demonstrate the vascular supply to the tumor for the surgeon to conserve as much
      normal parenchyma as possible. We propose that helical CT combined with 3-D
      volume rendering provides all of the information required for preoperative
      evaluation and intraoperative management of nephron sparing surgery cases. We
      prospectively evaluated the role of 3-D volume rendering CT in 60 patients
      undergoing nephron sparing surgery for renal cell carcinoma at the Cleveland
      Clinic Foundation. MATERIALS AND METHODS: Triphasic spiral CT was performed
      preoperatively in 60 consecutive patients undergoing nephron sparing surgery for
      renal neoplasms. A 3 to 5-minute videotape was prepared using volume rendering
      software which demonstrated the position of the kidney, location and depth of
      extension of the tumor(s), renal artery(ies) and vein(s), and relationship of the
      tumor to the collecting system. These videotapes were viewed by a radiologist and
      urologist in the operating room at surgery, and immediately correlated with
      surgical findings. Corresponding renal arteriograms of 19 patients were
      retrospectively compared to 3-D volume rendering CT and operative findings.
      RESULTS: A total of 97 renal masses were identified in 60 cases evaluated with 3
      D volume rendering CT before nephron sparing surgery. There were no complications
      related to the 3-D protocol and 3-D rendering was successful in all patients. The
      number and location of lesions identified by 3-D volume rendering CT were
      accurate in all cases, while enhancement and diagnostic characteristics were
      consistent with pathological findings in 95 of 97 tumors (98%). Of 77 renal
      arteries identified at surgery 74 were detected by 3-D volume rendering CT (96%).
      Helical CT missed 3 small accessory arteries, including 1 in a cross fused
      ectopic kidney. All major venous branches and anomalies were identified,
      including 3 circumaortic left renal veins. Of 69 renal veins identified at
      surgery 64 were detected by 3-D volume rendering CT (93%). All 5 renal veins
      missed by CT were small, short, duplicated right branches of the main renal vein.
      Renal fusion and malrotation anomalies were correctly identified in all 4
      patients. CONCLUSIONS: The 3-D volume rendering CT accurately depicts the renal
      parenchymal and vascular anatomy in a format familiar to most surgeons. The data
      integrate essential information from angiography, venography, excretory urography
      and conventional 2-D CT into a single imaging modality, and can obviate the need
      for more invasive imaging. Additionally, the use of videotape in an
      intraoperative setting provides concise, accurate and immediate 3-D information
      to the surgeon, and it has become the preferred means of data display for these
      procedures at our center.

PMID- 10081847
TI  - Is there a difference in outcome when treating traumatic intraperitoneal bladder
      rupture with or without a suprapubic tube?
AB  - PURPOSE: Primary bladder repair with a suprapubic tube is considered to be
      effective for managing intraperitoneal bladder injury. We compared the outcomes
      of suprapubic tube placement and no suprapubic tube for this injury. MATERIALS
      AND METHODS: We reviewed the charts of 31 men and 3 women with a mean age of 28.5
      years who required emergency operative repair without a cystogram of traumatic
      bladder injury from 1992 to 1997. Patient characteristics, mechanism of injury,
      associated injuries, and short and long-term complications were reviewed.
      RESULTS: Penetrating and blunt trauma occurred in 28 (82%) and 5 (15%) patients,
      respectively, while 1 had spontaneous bladder rupture. After primary bladder
      repair the bladder was drained with a suprapubic tube in 18 cases (53%) and a
      urethral catheter only in 16 (47%). There were no significant differences between
      the 2 groups with respect to mechanism of injury, patient age, location of injury
      in the bladder, coexisting medical illnesses, stability in the field or emergency
      room, or the bladder repair technique. The 18 patients treated with a suprapubic
      tube had an associated injury that resulted in 2 deaths, while 13 of the 16
      treated with urethral catheter drainage only had an associated injury and 1 died.
      Urological and nonurological complications in the suprapubic tube versus urethral
      catheter only group developed in 28 and 33 versus 19 and 19% of the cases,
      respectively (p <0.05). Followup ranged from 1 month to 4 years. No significant
      long-term morbidity was noted in either group. CONCLUSIONS: These data indicate
      that intraperitoneal bladder injuries may be equally well managed by primary
      bladder repair and urethral catheter drainage only versus suprapubic tube
      drainage.

PMID- 10081848
TI  - Bladder histological changes associated with chronic indwelling urinary catheter.
AB  - PURPOSE: Chronic urinary catheters induce histological changes in the bladder
      with time. The exact etiology of these changes is postulated to arise from
      inflammation and local tissue response. We elucidate the incidence of
      nonmalignant histological change in bladder biopsies of patients with chronic
      indwelling urinary catheters. MATERIALS AND METHODS: During 7 years 208 spinal
      cord injured patients underwent bladder biopsies as part of a surveillance
      program for vesical malignancy. All patients had chronic (more than 8.5 years)
      indwelling urethral or suprapubic catheters as definitive management for
      neurogenic voiding dysfunction. Biopsies were obtained from 4 to 6 sites within
      the bladder, including areas that were visually abnormal. All samples were
      routinely fixed with hematoxylin and eosin staining, and interpreted by an
      experienced pathologist. RESULTS: A total of 17 patients were identified with
      malignancy, including 10 with squamous cell carcinoma, 5 with transitional cell
      carcinoma and 2 with adenocarcinoma. Nonmalignant changes occurred in 48 patients
      (23%) with keratinizing squamous metaplasia or cystitis glandularis, each of
      which is considered a premalignant lesion. CONCLUSIONS: To our knowledge our
      study represents the largest group of spinal cord injured patients to undergo
      biopsy evaluation after chronic catheter use. A spectrum of inflammatory and
      proliferative pathological conditions were identified, which were predominantly
      inflammatory and squamous. The need to survey ongoing transitional mucosal
      changes in this population is underscored by the spectrum of histological
      abnormalities and the significant occurrence of malignant pathologies in our
      patients.

PMID- 10081849
TI  - Initial evaluation of the diagnostic performance of the new urinary bladder
      cancer antigen test as a tumor marker for transitional cell carcinoma of the
      bladder.
AB  - PURPOSE: We evaluated the diagnostic performance of the new noninvasive bladder
      cancer test on voided urine samples from patients with transitional cell
      carcinoma compared to symptomatic and asymptomatic controls. MATERIALS AND
      METHODS: Urinary bladder cancer antigen was measured in urine from 86 patients
      with active transitional cell carcinoma of the bladder (group 1), 76 patients
      free of transitional cell carcinoma as confirmed by cystoscopy at followup (group
      2), 25 patients with other benign urological diseases (group 3), 25 patients with
      other malignant pathological conditions (group 4) and 30 healthy subjects free of
      urological diseases (group 5). RESULTS: Mean urinary bladder cancer antigen
      concentrations were 104.84, 4.57, 11.79, 48.87 and 1.38 microg/l, for groups 1 to
      5, respectively, which was statistically different (p = 0.00005) except for
      groups 1 and 4 (p = 0.187). Sensitivity was 87.0% (95% confidence interval 79.2
      to 92.7) and specificity was 86.8% (77.1 to 93.5%), and both were optimized by
      receiver operating characteristics plot analysis at a threshold value of 9.74
      microg/l using asymptomatic (group 2) compared to known cancer (group 1) cases.
      CONCLUSIONS: Urinary bladder cancer antigen might have a role as a potential
      tumor marker for diagnosing transitional cell carcinoma of the bladder.

PMID- 10081850
TI  - Is everything all right if nothing seems wrong? A simple method of assessing the
      diagnostic value of endoscopic procedures when a gold standard is absent.
AB  - PURPOSE: We demonstrate a simple yet comprehensive method to evaluate the
      sensitivity of endoscopic procedures when no gold standard is available.
      MATERIALS AND METHODS: In 208 consecutive patients with superficial bladder
      cancer 328 endoscopies were performed to compare the sensitivity of white light
      and 5-aminolevulinic acid induced fluorescence endoscopy. Both procedures were
      performed during the same session. RESULTS: The maximum interval of observable
      sensitivity for 5-aminolevulinic acid induced fluorescence endoscopy ranged
      between 78 and 97.5%, and the best estimate for sensitivity based on realistic
      assumptions was 93.4% (95% confidence intervals 90 to 97.3). The best sensitivity
      estimate for white light endoscopy was 46.7% (95% confidence intervals 39.4 to
      54.3, maximum range 47.2 to 53%). CONCLUSIONS: This method to determine the
      maximum possible range of sensitivity estimates for endoscopic procedures without
      a gold standard is easily applied. Depending on the assumptions a range of
      reasonable scenarios can be constructed and the corresponding sensitivities can
      be reported. This approach gives fast and valid results, and could further
      indicate the diagnostic superiority of 5-aminolevulinic acid induced fluorescence
      compared to white light endoscopy.

PMID- 10081851
TI  - Effectiveness of a single immediate mitomycin C instillation in patients with low
      risk superficial bladder cancer: short and long-term followup.
AB  - PURPOSE: We analyze the impact of a single mitomycin C instillation in patients
      with low risk superficial bladder cancer with short and long-term followup.
      MATERIALS AND METHODS: A total of 131 patients with low risk superficial bladder
      cancer were included in a prospective randomized controlled trial. All patients
      had a 3 cm or less single, papillary, primary or recurrent tumor and were disease
      free for more than 1 year. Patients with muscular invasion, G3 tumor or bladder
      carcinoma in situ on pathological examination were excluded from study. The tumor
      was completely resected before patients were randomized into 2 arms of no further
      treatment (control group) and a single immediate instillation of 30 mg mitomycin
      C (mitomycin C group). Recurrences were considered early within the first 2 years
      of followup. RESULTS: At 24-month followup the recurrence-free interval was
      significantly increased, and recurrence, and recurrence and tumor per year rates
      were decreased in the mitomycin C compared to the control group. However, at long
      term followup these differences were not statistically significant and the
      recurrence-free interval curves were parallel. A shorter hospital stay and
      catheterization period were noted in the mitomycin C group compared to the
      control group, which were not significant. Early recurrences were concentrated in
      the first year in the control but not in the mitomycin C group. A significant
      relationship between early and late recurrences was found in the mitomycin C but
      not in the control group. CONCLUSIONS: Our analysis confirms the positive effect
      of a single immediate mitomycin C instillation in patients with low risk
      superficial bladder cancer. This benefit is limited to early recurrence and is
      not maintained with long-term followup. Thus, this approach is an alternative to
      observation or endovesical chemotherapy. Our study also suggests that cell
      implantation as a mechanism of early recurrence can be controlled with a single
      mitomycin C instillation.

PMID- 10081852
TI  - 5-year followup of a randomized prospective study comparing mitomycin C and
      bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish
      Norwegian Bladder Cancer Study Group.
AB  - PURPOSE: We report the 5-year followup of a randomized comparison of mitomycin C
      and bacillus Calmette-Guerin (BCG) in patients with superficial bladder
      carcinoma. Recurrence, progression and survival rates, crossover results,
      prognostic factors and long-term side effects were analyzed. MATERIALS AND
      METHODS: A total of 261 patients were enrolled in the study, and the inclusion
      criteria were primary Tis, dysplasia G2, T1 G3 and multiple recurrent Ta/T1 G1-2
      disease. Intravesical instillations of 40 mg. mitomycin C and 120 mg. Pasteur
      BCG, Danish strain 1331, were given for 2 years. RESULTS: After a median followup
      of 64 months 101 of the 250 evaluable patients (42%) were disease-free. A
      significant difference was noted in disease-free survival with BCG (p = 0.04),
      which was most pronounced for stage Tis disease. No difference in tumor
      progression, or crude or corrected survival was found between the 2 arms.
      Crossover treatment was successful in 39% of patients with second line BCG and
      19% with second line mitomycin C. Independent risk factors for progression were
      initial p53 status and stage. Only the completion of treatment was predictive of
      outcome for patients treated with BCG. Bladder shrinkage occurred in 2.4% of
      patients. CONCLUSIONS: Therapy with BCG was superior to mitomycin C for
      recurrence prophylaxis but no difference was found for progression and survival.

PMID- 10081853
TI  - Long-term consequences from bladder perforation and/or violation in the presence
      of transitional cell carcinoma: results of a small series and a review of the
      literature.
AB  - PURPOSE: Perforation of the bladder during transurethral resection is a worrisome
      complication for most urologists. Little is known about the consequences of
      seeding of tumor cells into the peritoneum or retroperitoneum. We reviewed
      several hospital patient databases as well as the literature to determine the
      outcome of such situations. MATERIALS AND METHODS: We performed a local multi
      institutional case and MEDLINE review using key words, such as bladder neoplasm,
      neoplasm seeding, perforation, rupture, transurethral resection, peritonitis and
      tumor. We also contacted several urologists and oncologists at major cancer
      centers in the United States and Europe regarding the incidence and followup of
      perforated/violated bladder cancer cases. RESULTS: There were 16 bladder
      violations in the presence of transitional cell carcinoma, including 2 partial
      cystectomies that had negative margins and no subsequent metastatic recurrences,
      a bladder tumor that was detected during suprapubic prostatectomy and
      perforations during transurethral resection (extraperitoneal in 4 cases and
      intraperitoneal in 9). Two patients died of sepsis and existing metastatic
      disease, respectively. The only recurrence among the remaining 11 patients
      developed after intraperitoneal bladder perforation during transurethral
      resection for Ta grade 2 tumor. Several anecdotal reports discussed local and
      distal tumor recurrences, suggesting that even superficial transitional cell
      carcinoma can behave aggressively if grown in an environment outside the bladder.
      However, these reports are rare. Any benefit of prophylactic chemotherapy was not
      proved. CONCLUSIONS: While perforation of the bladder during transurethral
      resection for cancer and the possibility of tumor implantation are matters of
      concern, our review demonstrates that few patients return with an extravesical
      tumor recurrence either locally or distally compared to those with a nonruptured
      bladder after resection. Although our patient sample is small and there are a
      limited number of reports in the literature, the risk of recurrence still exists
      and the urologist should be aware of its possibility. Since recurrences are
      usually rapid, they may easily manifest to the urologist at followup. However,
      one should also consider chest x-rays and/or computerized tomography to rule out
      recurrences that are not clinically obvious.

PMID- 10081854
TI  - Transurethral resection with perioperative instilation on interferon-alpha or
      epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a
      prospective randomized multicenter study--Finnbladder III.
AB  - PURPOSE: We evaluated the efficacy of single dose of interferon or epirubicin
      administered immediately after transurethral resection compared with
      transurethral resection only on the recurrence of primary (not recurrent)
      superficial bladder cancer. MATERIALS AND METHODS: A total of 283 patients with
      stages Ta to T1 primary superficial, grades 1 to 3 bladder cancer was randomized
      into study groups 1-transurethral resection only, 2-transurethral resection plus
      50 million units interferon-a2b and 3-transurethral resection plus 100 mg.
      epirubicin. Eligible for final analysis were 200 patients, including 66 in group
      1, 66 in group 2 and 68 in group 3. Patients were followed with cystoscopy every
      3 months for 2 years or until the initial recurrence. RESULTS: Group 3 had the
      most favorable outcome, since 45 of the 68 patients (66%) were without recurrence
      after 2 years compared to 24 of the 66 (37%) in group 2 and 26 of the 66 (40%) in
      group 1 (log rank test p <0.001). Side effects were mostly mild and transient,
      and no differences were found among the groups. CONCLUSIONS: A single 100 mg.
      dose of epirubicin given intravesically immediately after transurethral resection
      is safe, and significantly decreases the recurrence of primary superficial
      bladder cancer. A 50 million unit dose of interferon-alpha2b is well tolerated
      but it has no effect on recurrence as a single dose. The long-term effect of this
      treatment remains to be studied.

PMID- 10081855
TI  - Application of nocturnal electrobioimpedance volumetric assessment: a feasibility
      study in men without erectile dysfunction.
AB  - PURPOSE: Electrobioimpedance volumetric assessment is based on the principle of
      delivering a constant, nondetectable alternating current to a tissue segment. A
      potential difference measured between the electrodes is converted to impedance.
      Since impedance changes with variations in blood flow, penile volumetric change
      is measured noninvasively. We applied this procedure to the development of a new
      device to evaluate erectile activity nocturnally, and we report our findings in
      men with no history of erectile dysfunction. MATERIALS AND METHODS: Our study
      group comprised 10 men with a mean age of 44 years who had no history of erectile
      dysfunction. The NEVA device consists of a small recording device attached to the
      upper thigh, and 3 small adhesive electrode pads placed over the hip and on the
      penile base and glans, respectively. Each subject used the NEVA device for 2
      nights. RESULTS: Overall 20 nights of electrobioimpedance volumetric assessment
      were recorded. Tumescence monitoring revealed 3 to 6 erections per night per
      subject (mean 3.45) lasting 10 to 50 minutes (mean 17). As determined from the
      impedance measurements, mean volume change was 14.4 ml. with a 213% mean volume
      change over baseline. CONCLUSIONS: The new NEVA device is small, comfortable to
      wear and easy to use. It determines the number and duration of erectile events
      and percentage increase of blood volume changes during these events in normal men
      in a noninvasive manner. Future directions of study include a comparison to men
      with erectile dysfunction and analysis of the dynamic information of the NEVA
      data.

PMID- 10081856
TI  - Lengthening shortened penis caused by Peyronie's disease using circular venous
      grafting and daily stretching with a vacuum erection device.
AB  - PURPOSE: We evaluated the results of chronic intermittent stretching with a
      vacuum erection device after circumferential tunical incision and circular venous
      grafting in 4 patients with penile shortening from severe Peyronie's disease.
      MATERIALS AND METHODS: We performed complete circumferential tunical incision and
      covered the defect with a circular venous graft in 4 patients with shortened
      penis as a result of Peyronie's disease. Preoperative evaluation included
      determination of patient and partner expectations, potency status, measurement of
      penile length after intracavernous injection and color duplex ultrasonography to
      determine possible vascular communication. Lower saphenous, upper saphenous and
      deep dorsal veins served as graft materials. We advised patients to use a vacuum
      device on a daily basis for 6 months starting 1 month after surgery.
      Postoperative evaluations were done at 6 and 18 months postoperatively. RESULTS:
      At 6-month followup 1 patient who did not use the vacuum device gained 1 inch in
      penile length and was not available for further followup. The other 3 patients
      each gained 2 inches but had decreased erectile rigidity due to narrowing in the
      grafted area (hourglass deformity). One patient who wanted a more natural
      erection elected penile prosthesis implantation about 1 year after grafting. The
      remaining 2 patients gained 3 inches at 18-month followup and regained partial
      penile rigidity similar to preoperative erections when the hourglass deformity
      improved. All patients were satisfied and indicated that surgery improved
      psychological well-being as well as relationships with partners. CONCLUSIONS: The
      results in this small group are satisfactory. Our technique offers a reasonable
      solution for correction of penile shortening in patients with Peyronie's disease.

PMID- 10081857
TI  - Patient selection criteria in the surgical treatment of veno-occlusive
      dysfunction.
AB  - PURPOSE: We evaluated short and long-term results of simple and complex venous
      surgery in patients with veno-occlusive dysfunction unresponsive to maximum
      recommended doses of intracavernous alprostadil, who were selected with newly
      developed diagnostic indicators. MATERIALS AND METHODS: A total of 23 impotent
      men with a mean age of 41 years (range 20 to 50) underwent complex penile venous
      surgery. Only patients fulfilling at least 3 criteria were included in study. The
      criteria were mild cavernous leak assessed by cavernosometry (grades 1 and 2),
      more than 30% cavernous smooth muscle tissue (histomorphometric analysis), normal
      analogical corpus cavernosum electromyography recordings according to
      international standards, cavernosal oxygen tension greater than 65 mm. Hg at
      erection and age younger than 50 years. RESULTS: Of 23 patients 17 (74%) had
      normal erections within a year after surgery, and 5 of them (29%) complained of
      recurrent erectile dysfunction. At long-term followup 6 of 12 patients had
      spontaneous erections. CONCLUSIONS: Careful selection with advanced diagnostic
      techniques should be mandatory before performing venous surgery in patients with
      high degree veno-occlusive dysfunction as the only alternatives are major
      therapeutical solutions.

PMID- 10081858
TI  - Long-term results following adjuvant chemotherapy in patients with clinical stage
      I testicular nonseminomatous malignant germ cell tumors with high risk factors.
AB  - PURPOSE: We determine the efficacy and safety of 2 cycles of adjuvant
      chemotherapy after orchiectomy in patients with high risk clinical stage I
      nonseminomatous germ cell tumor of the testis as an alternative to
      retroperitoneal lymphadenectomy or watchful waiting. MATERIALS AND METHODS: A
      total of 60 consecutive patients with clinical stage I nonseminomatous germ cell
      tumor of the testis and 1 or more risk factors were entered into this prospective
      study. Criteria for high risk were embryonal cell carcinoma, tumor invasion of
      blood or lymph vessels, or tumor stage pT2 or greater. Chemotherapy consisted of
      2 cycles of cisplatin, vinblastine and bleomycin or bleomycin, etoposide and
      cisplatin. RESULTS: Of the 60 patients 1 refused chemotherapy and 1 was lost to
      followup 1.5 years after treatment. The remaining 58 patients have been followed
      for a median of 93 months (range 32 to 146). World Health Organization grade 4
      toxicity was observed in 9 of the 116 chemotherapy cycles, and consisted mainly
      of transient neutropenia and thrombocytopenia. No significant long-term sequelae
      were detected. There was 1 relapse after 22 months in a patient with adult
      teratoma in the ipsilateral region of the iliac vessels who remained disease-free
      85 months after surgical excision of the lesion. Another patient had a seminoma
      in the contralateral testicle with interaortocaval lymph node metastases 7.5
      years after adjuvant chemotherapy. The remaining 56 men are without relapse or
      contralateral tumor to date. CONCLUSIONS: We recommend adjuvant chemotherapy as
      an efficient therapeutic alternative to retroperitoneal lymphadenectomy for high
      risk nonseminomatous germ cell tumor of the testis.

PMID- 10081859
TI  - Repeat vasectomy reversal after initial failure: overall results and predictors
      for success.
AB  - PURPOSE: We review the treatment outcomes for microsurgical reconstruction
      following failed vasectomy reversal and identify predictors for success.
      MATERIALS AND METHODS: We performed a retrospective review of our experience with
      microsurgical reconstruction in 41 men who underwent 1 or more prior unsuccessful
      vasectomy reversal procedures. Of these patients 20 underwent bilateral (16) or
      unilateral (4) vasoepididymostomy, 11 underwent bilateral (7) or unilateral (4)
      vasovasostomy and 10 underwent unilateral vasoepididymostomy with contralateral
      vasovasostomy. Postoperative followup consisted of serial semen analyses and
      telephone interviews. RESULTS: Patency and pregnancy followup data were available
      in 33 and 31 patients, respectively. Five couples had ongoing uncorrected female
      factor infertility problems and were not included in pregnancy rate calculations.
      Mean obstructive interval was 10.6 years. Overall patency and pregnancy rates
      were 79 and 31%, respectively. Mean total motile sperm count for patients
      demonstrating patency at followup was 38.0 million. History of conception with
      the current partner was predictive of future conception with 4 of 5 nonremarried
      couples (80%) initiating a pregnancy versus 3 of 18 remarried couples (17%) (p =
      0.006). Other factors, including smoking history and obstructive interval, did
      not correlate with postoperative success. Reconstruction with vasovasostomy on at
      least 1 side trended toward improved patency (p = 0.17) and pregnancy rates (p =
      0.15), although they did not assume statistical significance. CONCLUSIONS:
      Microsurgical reconstruction following failed vasectomy reversal is associated
      with high patency and moderate pregnancy rates at short-term followup. In our
      series previous conception with the current partner was predictive of future
      conception after reconstruction. Urologists performing repeat vasectomy reversal
      must be familiar with microsurgical techniques, since almost three-quarters of
      patients will require at least unilateral vasoepididymostomy.

PMID- 10081860
TI  - Assisted reproduction technology for patients with congenital bilateral absence
      of vas deferens.
AB  - PURPOSE: We investigate the frequency of cystic fibrosis transmembrane
      conductance regulator gene mutations in Japanese patients with congenital
      bilateral absence of the vas deferens, and assess treatment outcomes of assisted
      reproduction interventions. MATERIALS AND METHODS: In 10 Japanese patients with
      bilateral congenital absence of the vas deferens genetic analysis was performed
      for known frequent mutations of the cystic fibrosis transmembrane conductance
      regulator gene using polymerase chain reaction amplification followed by dot-blot
      hybridization with the allele-specific oligonucleotide probes and direct
      sequencing. Intracytoplasmic sperm injection using spermatozoa retrieved from the
      testes was performed in 7 of the couples. RESULTS: No known mutations of the gene
      were detected in the patients. However, analysis of the polythymidine tract
      polymorphism in intron 8 revealed 30% allele frequency of 5T. Pregnancy was
      achieved in 7 cycles of intracytoplasmic sperm injection using spermatozoa
      retrieved from the testes. CONCLUSION: The 5T variant in intron 8 polythymidine
      tract was identified with high allelic frequency in Japanese patients with
      congenital bilateral absence of the vas deferens, suggesting that the disease in
      Japan is also partially caused by this particular mutation of the cystic fibrosis
      transmembrane conductance regulator gene. Modern assisted reproduction technology
      offers an important option for patients with congenital bilateral absence of the
      vas deferens.

PMID- 10081861
TI  - Effect of repeated ejaculation on semen quality in spinal cord injured men.
AB  - PURPOSE: We evaluate the effect of repeated ejaculations on semen quality in
      spinal cord injured men. MATERIALS AND METHODS: The study included 19 spinal cord
      injured men with anejaculation. Semen was obtained by penile vibratory
      stimulation in the clinic and patients were instructed in the technique.
      Optimized vibration parameters were used (2.5 mm. amplitude at 100 Hz.). Penile
      vibratory stimulation was performed at least once a week for 12 months. Semen
      quality was examined at baseline and every 3 months during the 1-year study
      period. Hormonal assays were also performed at each visit. In 9 patients
      unilateral testicular biopsy was done at baseline and at the end of the 12
      months. RESULTS: Normal sperm counts and low motility were seen at baseline. No
      semen parameter significantly changed during the 12 months of repeated
      ejaculation. All hormonal assays during the entire study were within normal range
      and no significant change was observed. Of the 9 biopsies 6 (67%) showed normal
      spermatogenesis at baseline and no convincing qualitative changes in testicular
      histology were seen after repeated ejaculation. CONCLUSIONS: Repeated ejaculation
      in spinal cord injured men does not change the typically poor semen quality.
      Therefore, stagnation in the seminal ducts due to infrequent ejaculation is not
      the etiology of the poor semen quality in these patients.

PMID- 10081862
TI  - Male infertility--realistic treatment options.

PMID- 10081863
TI  - The relative amount of epithelium, muscle, connective tissue and lumen in
      prostatic hyperplasia as a function of the mass of tissue resected.
AB  - PURPOSE: The relative amounts of epithelium, connective tissue, muscle and gland
      lumen in benign prostatic hyperplasia have been reported but they have not been
      correlated with prostate size. We determine if the relative amount of prostatic
      tissue varies with prostate size. MATERIALS AND METHODS: Paraffin blocks of
      transurethrally resected prostate tissue were randomly chosen from the archives
      of 58 patients with benign prostatic hyperplasia. Two new slides per patient were
      made and stained with prostate specific antigen or Masson trichrome,
      respectively. A total of 20 images from each slide were captured using a high
      resolution camera, digitized and analyzed with computer software for the relative
      percentage of the various tissue components. RESULTS: As the amount of prostate
      tissue resected increased from less than 10 to greater than 70 gm. the epithelium
      had a 4-fold increase from 5.37 to 21.92%, the muscle component had a 42%
      decrease from 28.46 to 16.62%, the lumen doubled from 7.05 to 14.01% and the
      connective tissue remained relatively unchanged from 35.58 to 31.53%. There was a
      statistically significant difference in all components of prostatic tissue except
      for connective tissue when comparing prostates less than 30 versus greater than
      30 gm., including epithelium 6.52 versus 16.10% (p <0.01), muscle 28.45 versus
      20.78% (p <0.01), lumen 7.42 versus 14.58% (p <0.01) and connective tissue 35.74
      versus 32.45% (p <0.06). The stroma-to-epithelium and muscle-to-epithelium ratios
      each had a 9-fold decline (p = 0.01). CONCLUSIONS: As the prostate increases in
      size, there is statistically significant more epithelium and lumen, and less
      muscle tissue.

PMID- 10081864
TI  - Longitudinal prostate growth rates during 5 years in randomly selected community
      men 40 to 79 years old.
AB  - PURPOSE: We estimate the rate of prostate growth in randomly selected healthy
      community dwelling men. MATERIALS AND METHODS: Prostate volume in an age
      stratified random sample of 631 white male residents of Olmsted County, Minnesota
      40 to 79 years old without prior prostate surgery or prostate cancer was measured
      up to 4 times by transrectal ultrasound during a followup period of almost 7
      years. RESULTS: Estimated prostate growth rates increased with increasing age.
      However, the estimated average annual change was 1.6% across all age groups.
      Estimated prostate growth rates were high depending on baseline prostate volume
      with higher growth rates for men with larger prostates. CONCLUSIONS: While there
      is wide variability in prostate growth rates on an individual level, prostate
      volume appears to increase steadily at about 1.6% per year in randomly selected
      community men.

PMID- 10081865
TI  - Health related quality of life in older men without prostate cancer.
AB  - PURPOSE: We measured health related quality of life in a population of normal
      older men for use as controls in studies of older men treated for prostate
      cancer. MATERIALS AND METHODS: A statistically valid, population based sample of
      older men without prostate cancer completed a validated quality of life
      questionnaire that addressed impairment in the physical, mental, urinary, bowel
      and sexual domains. General and disease targeted health related quality of life
      was measured by the RAND 36-Item Health Survey and University of California, Los
      Angeles Prostate Cancer Index, respectively. RESULTS: Overall approximately a
      third of normal older men reported some degree of urinary leakage, while a third
      claimed some degree of rectal dysfunction and almost two-thirds acknowledged
      significant difficulty with erection. CONCLUSIONS: Older men in a randomly
      selected, population based sample do not have perfectly normal urinary
      continence, bowel function or sexual potency. By collecting data before treatment
      and following subjects longitudinally investigators may ensure that health
      related quality of life changes are analyzed in the context of any impairment
      that may have been present at baseline. If a longitudinal study is not feasible,
      a control group of men who are similar in age and other demographic variables
      must be used.

PMID- 10081866
TI  - Radical retropubic prostatectomy reduces symptom scores and improves quality of
      life in men with moderate and severe lower urinary tract symptoms.
AB  - PURPOSE: We determine the impact of radical retropubic prostatectomy on lower
      urinary tract symptoms and quality of life due to urinary problems in men with
      clinically localized prostate cancer. MATERIALS AND METHODS: The American
      Urological Association (AUA) symptom index, a symptom problem index and a quality
      of life due to urinary problems question were administered to 104 men before and
      12 months after radical prostatectomy. Urinary continence and satisfaction with
      the decision to undergo radical prostatectomy were also examined. RESULTS: In men
      with moderate or severe baseline urinary symptoms (AUA score 8 or greater) the
      total AUA symptom, symptom problem and quality of life question scores decreased
      by 51 (-6.39), 57 (-4.22) and 25% (-0.65), respectively, after radical
      prostatectomy. Except for nocturia statistically significant improvements were
      observed for all questions captured by the AUA symptom index. Radical
      prostatectomy did not significantly change mean AUA symptom score or symptom
      problem index in men with mild urinary symptoms (AUA score less than 8). In men
      with moderate or severe urinary symptoms radical prostatectomy significantly
      improved quality of life due to urinary problems. Although 10% of men exhibited
      some degree of clinically relevant stress incontinence, 98% were very satisfied
      or satisfied with the decision to undergo radical prostatectomy. CONCLUSIONS: In
      men with moderate or severe urinary symptoms radical prostatectomy improves lower
      urinary tract symptoms and quality of life due to urinary problems. The overall
      beneficial impact on voiding makes radical prostatectomy an attractive treatment
      option for clinically localized prostate cancer.

PMID- 10081867
TI  - Downward trend in prostate cancer mortality in Quebec and Canada.
AB  - PURPOSE: If new treatment strategies and screening for prostate cancer are
      effective they should reduce prostate cancer mortality. In this review we
      monitored prostate cancer mortality rates in Quebec and in Canada. MATERIALS AND
      METHODS: We obtained data on all deaths from prostate cancer between 1976 and
      1997 in Quebec, and 1976 and 1996 in Canada. We calculated age standardized
      mortality rates and assessed changes with time. RESULTS: Prostate cancer
      mortality rates increased regularly until 1991 in Quebec and Canada. After 1991
      the rates decreased moderately until 1995 and then more markedly in 1996. There
      was a further decline in 1997 in Quebec. Overall, age standardized prostate
      cancer mortality rates declined by 23% in Quebec between 1991 and 1997, and by
      9.6% in Canada between 1991 and 1996. The mortality decline was observed for all
      age groups but was more pronounced among men younger than 75 years. CONCLUSIONS:
      Until 1995 the trends in prostate cancer mortality in Quebec and Canada were
      similar to those observed in the United States. Our data suggest that a sharper
      decline has occurred since 1995. It is of primary importance to identify the
      causes of the mortality decline. As prostate cancer mortality rates declined
      relatively early after the initiation of widespread screening with prostate
      specific antigen, it is unlikely that screening has as yet contributed in a major
      way to the decline. It is more likely that the mortality reduction is a
      consequence of better prostate cancer management or improved treatment
      modalities.

PMID- 10081868
TI  - The changing pattern of prostate cancer at the time of diagnosis: characteristics
      of screen detected prostate cancer in a population based screening study.
AB  - PURPOSE: We describe the clinical and pathological features of prostate cancer
      diagnosed through serum prostate specific antigen (PSA), digital rectal
      examination and transrectal ultrasonography in a population based randomized
      screening study. MATERIALS AND METHODS: Between November 1993 and June 1997,
      20,632 volunteers 55 to 76 years old were included in the study. In the screening
      arm 9,776 men underwent digital rectal examination, transrectal ultrasound and
      serum PSA determination. Biopsies were taken if the digital rectal examination
      and/or transrectal ultrasound findings were abnormal or if PSA was 4 ng/ml or
      greater. A total of 2,262 men underwent biopsy and 474 cases of prostate cancer
      were diagnosed. RESULTS: The pretreatment data were complete in 459 men, of whom
      78% had clinically organ confined disease. Bone or lymph node metastases were
      seen in 8 cases (1.7%). Of 172 men who underwent radical prostatectomy 2 had
      lymph node metastases. Overall 66.3% of men treated with radical prostatectomy
      had organ confined disease. CONCLUSIONS: Comparison of the characteristics of
      prostate cancer detected through screening of the general population with those
      in a population based cohort of men in which there was no organized screening
      revealed stage reduction, primarily with regard to number of metastatic cases.
      Whether this stage reduction will lead to a decrease in disease specific
      mortality remains unknown until the study is completed and the end point of
      prostate cancer specific mortality is evaluated.

PMID- 10081869
TI  - Prostate specific antigen nadir achieved by men apparently cured of prostate
      cancer by radiotherapy.
AB  - PURPOSE: The role of prostate specific antigen (PSA) nadir in the definition of
      disease freedom after radiotherapy of prostate cancer is controversial. We
      evaluate post-irradiation PSA nadir in men apparently cured of this disease.
      MATERIALS AND METHODS: From 1984 to 1993, 354 men with clinical stage T1T2N0
      prostate cancer were treated with radioactive 125iodine prostate implant followed
      by external beam radiation. Median pretreatment PSA was 8.4 ng/ml (range 0.3 to
      188). Of these men 250 are disease-free and median pretreatment PSA was 6.5 ng/ml
      (range 0.3 to 123). Treatment failure is defined as 3 consecutive PSA increases
      above nadir. Median followup is 7 years (range 5 to 14 years) for the 250 disease
      free men and 6 years (range 0.5 to 14) for all 354 men. RESULTS: PSA nadir 0.5
      ng/ml or less was achieved by 98% of all disease-free men (244 of 250) with
      minimum 5-year followup, including 87% (217) who achieved nadir 0.2 ng/ml or
      less. All 27 disease-free men with minimum 10-year followup had a PSA nadir of
      0.5 ng/ml or less. PSA nadir significantly correlated with disease-free survival
      by receiver operator characteristics curve analysis (0.93 area under the curve)
      in all 354 men. CONCLUSIONS: PSA nadir is the fundamental measurement that
      determines possible cure after radiotherapy. Except for perhaps rare occasions,
      men must at least achieve a nadir of 0.5 ng/ml. or less to be cured of prostate
      cancer by irradiation. However, the prognostic value of this nadir level depends
      on most men achieving a nadir of 0.2 ng/ml or less. Disease freedom for
      radiotherapy, defined as achievement and maintenance of PSA nadir 0.5 ng/ml or
      less, is reasonable.

PMID- 10081870
TI  - Ultrasensitive detection of prostate specific antigen in the followup of 422
      patients after radical prostatectomy.
AB  - PURPOSE: We validated our ultrasensitive prostate specific antigen (PSA) assay
      based on lyophilization and 4-fold concentration of patient sera with the
      clinical long-term followup and according to histopathological characteristics of
      422 patients treated with radical retropubic prostatectomy for prostate cancer.
      MATERIALS AND METHODS: Each serum sample was divided into 2 aliquots for standard
      and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the
      same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an
      increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in
      concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier
      analysis of standard and ultrasensitive detection results was done, and findings
      were correlated with pathological stage, Gleason grade, total cancer volume,
      Gleason grade 4 cancer volume and margin status. Significance of earlier
      detection in ultrasensitive versus standard detection was calculated with the log
      rank (Mantel-Cox) test with p <0.05 considered significant. RESULTS: Of 442
      patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%)
      demonstrated early failure on the ultrasensitive assay which was later confirmed
      on the standard assay, 37 (42%) had failure simultaneously on both assays and 23
      (26%) had failure on the ultrasensitive but remained disease-free on the standard
      assay. Average time for ultrasensitive assay detection of recurrence was 288 days
      (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier
      detection of recurrence with the ultrasensitive assay, and close correlation with
      pathological stage, Gleason grade, margin status and Gleason grade 4 cancer
      volume. Time advantages of ultrasensitive versus standard detection were greater
      for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for
      small, low grade tumors. All patients who had positive results on the standard
      assay had a previous (28) or simultaneous (37) positive ultrasensitive result.
      With standard detection 25% of all relapses were evident within the first year of
      surgery and with ultrasensitive detection the percentage increased to 85.7%. On
      both assays 334 patients remained free of biochemical recurrence. CONCLUSIONS:
      Our ultrasensitive PSA assay is useful for early detection of biochemical relapse
      after radical retropubic prostatectomy. It not only provides the same accuracy as
      conventional PSA assays but also offers the advantage of detecting recurrence
      about 300 days earlier. Thus, long-term results of radical retropubic
      prostatectomy series can be calculated sooner. The clinical impact of this assay
      will be obvious once curative treatment options are available if applied at the
      earliest time of evident tumor recurrence.

PMID- 10081871
TI  - Retrospective comparison of radical retropubic prostatectomy and 125iodine
      brachytherapy for localized prostate cancer.
AB  - PURPOSE: Favorable results with 125iodine (I) brachytherapy have been reported in
      select patients with localized prostate cancer. We evaluate the results of
      radical prostatectomy in patients matched for similar pretreatment
      clinicopathological characteristics. MATERIALS AND METHODS: From May 1983 to
      April 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in
      1,952 men (mean age plus or minus standard deviation 63+/-7 years), of whom 1,364
      had Gleason score 6 or less on preoperative needle biopsy, a preoperative serum
      prostate specific antigen (PSA) value available and clinical stage T1 or T2
      disease. We categorized all patients by preoperative Gleason score, preoperative
      PSA and clinical stage. For each Gleason score-by-PSA stratum we randomly
      selected by computer the number of men necessary to achieve the same overall
      distribution of clinical characteristics as in a series of patients treated with
      brachytherapy. All men were followed with semiannual PSA measurements and annual
      digital rectal examinations. Serum PSA greater than 0.3 ng/ml was considered
      evidence of cancer recurrence. Simple univariate statistics were used to compare
      clinical characteristics between series, and 7-year recurrence-free survival was
      estimated using Kaplan-Meier product limit estimates. To avoid a possible chance
      extreme result from 1 random sample we estimated 7-year recurrence-free survival
      in 5 computer selected random samples of our population. RESULTS: Mean 7-year
      recurrence-free survival was 84% (95% confidence intervals 78 to 89) for the
      radical prostatectomy series compared to 79% (confidence intervals not provided)
      for the 125I brachytherapy series. CONCLUSIONS: Radical prostatectomy yielded a
      proportionately but not statistically significant higher 7-year probability of
      nonprogression than 125I brachytherapy in patients with favorable
      clinicopathological characteristics. Comparisons are confounded by residual
      differences in clinicopathological features of tumors between groups and
      different treatment end points to determine outcomes. Further prospective,
      randomized clinical trials are required for valid comparisons.

PMID- 10081872
TI  - Charge and length of hospital stay analysis of radical retropubic prostatectomy
      and transperineal prostate brachytherapy.
AB  - PURPOSE: For the treatment of clinically localized prostate cancer radical
      retropubic prostatectomy with its attendant hospital stay should be associated
      with higher charges than transperineal prostate brachytherapy. We report a
      comparative case series to determine patient charges and length of
      hospitalization of 2 modalities of monotherapy for localized prostate cancer.
      MATERIALS AND METHODS: A total of 35 consecutive patients with clinically
      localized prostate cancer underwent radical retropubic prostatectomy (16) or
      transperineal prostate brachytherapy (19) at the Arthur James Cancer Hospital and
      Research Institute. Complete charge and length of hospital stay data were
      collected for each patient. Total charges were calculated and the 2 modalities
      were compared. RESULTS: Charge data were available in 33 cases. Average total
      charges in the prostatectomy and brachytherapy groups were $15,097 and $21,025,
      respectively ($5,928 difference, p <0.0001). The difference increased further
      when outliers were excluded from study. Average length of hospital stay and
      average charge in the prostatectomy group were 3.8 days and $1,897. The higher
      charges for transperineal prostatic brachytherapy were due to dosimetry
      calculations, radioactive seeds and seed implantation. CONCLUSIONS: At our
      institution the average total charges for transperineal prostate brachytherapy
      are significantly higher than those for radical retropubic prostatectomy.

PMID- 10081873
TI  - Bone mineral density in men treated with synthetic gonadotropin-releasing hormone
      agonists for prostatic carcinoma.
AB  - PURPOSE: We evaluate the relationship between the use of synthetic gonadotropin
      releasing hormone (Gn-RH) agonists and bone loss in men. MATERIALS AND METHODS:
      Bone mineral density and parameters of mineral metabolism were evaluated in 12
      patients with stage C prostatic carcinoma before and after 6, 12 and 18 months of
      treatment with 3.75 mg. triptorelin intramuscularly every 4 weeks. RESULTS: Of
      the 12 patients 9 were evaluated after 6, 7 after 12 and 6 after 18 months of
      therapy. In comparison with month 0, the lumbar and femoral neck bone mineral
      density tended to decrease at month 6 (-3 and -2.7%, p = 0.31 and 0.17,
      respectively), at month 12 (-4.6 and -3.9%, p = 0.13 and 0.13) and at month 18 (
      7.1 and -6.6%, p = 0.12 and 0.027). A second analysis revealed that the lumbar
      and femoral neck bone mineral density was significantly decreased on the last
      evaluation compared to month 0 (p = 0.05 and 0.028, respectively). The serum
      osteocalcin was increased during treatment, suggesting an accelerated bone
      turnover in men treated with Gn-RH agonists. CONCLUSIONS: The use of Gn-RH
      agonists in men may induce an accelerated bone loss. Further studies are needed
      to confirm these results and to evaluate the incidence of osteoporotic fractures
      in men treated with Gn-RH agonists.

PMID- 10081874
TI  - Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for
      pTxN+ prostate cancer: a matched comparison.
AB  - PURPOSE: Untreated stage pTxN+ prostate cancer is associated with a poor outcome.
      Monotherapy (surgery, radiation, hormonal therapy) alone is associated with a
      high progression rate. We evaluate whether radical prostatectomy and pelvic
      lymphadenectomy plus early adjuvant orchiectomy impart a survival advantage
      compared to pelvic lymphadenectomy and orchiectomy alone in a matched cohort of
      patients. MATERIALS AND METHODS: Between 1966 and 1995, 382 and 79 patients with
      stage pTxN+ prostate cancer underwent pelvic lymphadenectomy and radical
      prostatectomy plus early adjuvant orchiectomy (within 3 months of prostatectomy),
      and pelvic lymphadenectomy and orchiectomy only, respectively. We selected 79
      matched controls from the prostatectomy plus orchiectomy group for the
      orchiectomy group. Patients were matched according to the number of positive
      nodes, clinical grade, clinical stage, age, year of surgery and preoperative
      prostate specific antigen (after 1987). The Kaplan-Meier method and stratified
      Cox proportional hazards model were used to estimate overall and cause specific
      survival for the 2 groups. RESULTS: There was an overall survival advantage at 10
      years for the prostatectomy plus orchiectomy (66+/-6%) compared to the
      orchiectomy (28+/-6%) group (p <0.001, risk ratio 0.36, 95% confidence interval
      0.20 to 0.66). There was also an advantage in cause specific survival at 10 years
      in the prostatectomy plus orchiectomy (79+/-5%) versus the orchiectomy (39+/-7%)
      group (p <0.001, relative risk 0.28, 95% confidence interval 0.13 to 0.59). After
      1987, when matched on preoperative prostate specific antigen, the apparent
      survival advantage at 5 years with radical prostatectomy was smaller (79+/-8
      versus 63+/-9% orchiectomy) and not significant (p = 0.19). CONCLUSIONS: This
      retrospective study of patients with stage pTxN+ PC suggests that radical
      prostatectomy with early adjuvant orchiectomy may provide a significant advantage
      in overall and cause specific survival compared to orchiectomy alone.

PMID- 10081875
TI  - Androgen receptor expression in prostatic intraepithelial neoplasia and cancer.
AB  - PURPOSE: Androgen receptors are present in virtually all epithelial cells of the
      prostate, including benign epithelium, high grade prostatic intraepithelial
      neoplasia and cancer. However, there have been variable results regarding the
      clinical significance of cells expressing androgen receptors in prostate cancer.
      We evaluated the predictive accuracy of androgen receptor expression in prostatic
      intraepithelial neoplasia and cancer for clinical progression and survival in
      patients with organ confined prostate cancer treated with radical prostatectomy.
      MATERIALS AND METHODS: The study consisted of 172 previously untreated patients
      who underwent radical prostatectomy at our clinic between 1987 and 1991 with
      intermediate to high grade (Gleason score 6 to 9), pathological stage T2 cancer
      and negative surgical margins. Mean followup was 7.4 years (range 1.2 to 10.1).
      Mouse monoclonal anti-human androgen receptor antibody was used for
      immunohistochemical studies on select tissue sections from each case. We counted
      100 nuclei from 3 separate areas of benign epithelium, prostatic intraepithelial
      neoplasia and cancer (total 300 nuclei for each diagnostic category) for each
      case. Mean nuclear androgen receptor expression was determined from the mean of
      the individual cases for each diagnostic category. Intensity was also evaluated
      using a subjective scale from 0 (no staining) to 3 (strong staining). We
      determined the correlation of clinical progression and the number of androgen
      receptor immunoreactive prostatic intraepithelial neoplasia or cancer nuclei, and
      then performed multivariate analysis which included deoxyribonucleic acid ploidy,
      radical prostatectomy Gleason score and preoperative serum prostate specific
      antigen using the Cox proportional hazards model. Progression was defined as a
      positive biopsy, positive bone scan or biochemical progression (postoperative
      serum prostate specific antigen greater than 0.2 ng./ml.). RESULTS: Nuclear
      immunoreactivity for androgen receptors was observed in all cases. Mean percent
      of immunoreactive nuclei was higher in benign epithelium than in prostatic
      intraepithelial neoplasia and cancer (56.3, 46.1 and 53.6%, respectively,
      pairwise comparisons p <0.05 for each pair). With rare exceptions, basal cells in
      benign epithelium and prostatic intraepithelial neoplasia were negative. The most
      intense nuclear staining was observed in benign epithelium. Immunoreactivity was
      also faint but detectable in the cytoplasm in prostatic intraepithelial neoplasia
      but not in benign epithelium or cancer. Mean number of androgen receptor
      immunoreactive nuclei in prostatic intraepithelial neoplasia and cancer was not a
      significant univariate or multivariate predictor of clinical and/or biochemical
      progression, or all cause survival (all p >0.05). CONCLUSIONS: Androgen receptor
      expression was present in all cases of benign epithelium, prostatic
      intraepithelial neoplasia and cancer. The greatest extent and intensity of
      expression were observed in benign epithelium, with about half of the nuclei
      showing intense immunoreactivity. The number of androgen receptor immunoreactive
      nuclei in prostatic intraepithelial neoplasia and cancer in patients with organ
      confined prostate cancer treated with radical prostatectomy was not predictive of
      progression or survival.

PMID- 10081876
TI  - Androgen receptor expression in prostate cancer lymph node metastases is
      predictive of outcome after surgery.
AB  - PURPOSE: Androgens mediate the growth of prostate cancer cells. The predictive
      value of androgen receptor immunostaining in patient outcome is controversial. We
      studied the expression of androgen receptors in a large series of patients with
      node positive cancer, and correlated the results with clinical progression and
      survival. MATERIALS AND METHODS: We evaluated 197 patients with a mean age of
      65.5 years who had node positive adenocarcinoma, and who underwent bilateral
      pelvic lymphadenectomy and/or radical prostatectomy at our clinic between 1987
      and 1992. Mean followup was 6.3 years. Immunohistochemical studies were performed
      using an antihuman androgen receptor monoclonal antibody. In each case 100 nuclei
      were counted from 3 separate areas (total 300 nuclei per diagnostic category) of
      benign epithelium, cancer and lymph node metastases. Mean androgen receptor
      expression was determined from the mean of the individual cases. The intensity of
      immunoreactivity was evaluated on a scale of 0-no staining to 3-strong staining.
      We assessed the correlation of androgen receptor immunoreactivity,
      deoxyribonucleic acid ploidy, Gleason score and preoperative serum prostate
      specific antigen (PSA) with clinical progression, all cause survival and cancer
      specific survival using the Cox proportional hazards model. Clinical progression
      was defined as a positive bone scan. RESULTS: There was heterogeneous staining in
      the majority of cells in benign and malignant prostatic epithelium. The mean
      number of immunoreactive nuclei was similar in all groups (56, 53 and 56% of
      benign epithelium, cancer and lymph node metastases, respectively). Pairwise
      comparisons revealed that the only significant difference was between benign
      epithelium and cancer (p = 0.001) with greater immunoreactivity in benign
      epithelium. Intensity was lower in benign epithelium than in cancer and lymph
      nodes (p <0.05). Androgen receptor expression in lymph node metastases was
      associated with all cause and cancer specific survival on univariate analysis (p
      = 0.03 and 0.04, respectively). The 7-year cause specific survival was 98, 94 and
      86% in patients with 51 to 69, less than 50 and greater than 70% androgen
      receptor expression in lymph node metastases, respectively (p <0.05). The
      association of androgen receptor expression in lymph node metastases was
      significant on multivariate analysis for cancer specific survival (p = 0.021) but
      not all cause survival (p = 0.16) after controlling for Gleason score,
      deoxyribonucleic acid ploidy and preoperative PSA. Androgen receptor
      immunoreactivity in lymph nodes was not a significant univariate or multivariate
      predictor of clinical progression, while androgen receptor expression in the
      primary cancer was not predictive of clinical progression or survival (p >0.05).
      CONCLUSIONS: Androgen receptor expression was similar in benign epithelium,
      primary cancer and lymph node metastases with approximately half of the
      epithelial cell nuclei staining. Androgen receptor immunoreactivity in lymph node
      metastases was predictive of cancer specific but not all cause survival in
      univariate and multivariate models. Gleason score was the strongest predictor of
      all cause survival in this cohort of patients. Our results indicate that it may
      be clinically useful to determine lymph node androgen receptor expression in men
      with advanced prostate cancer when combined with Gleason score and PSA.

PMID- 10081877
TI  - Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors
      of biochemical relapse after radical prostatectomy.
AB  - PURPOSE: Since radical prostatectomy is performed to cure prostate cancer,
      identification of markers enabling preoperative prediction of relapse after
      radical prostatectomy is essential to counsel and select patients for adjuvant
      therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been
      associated with aggressiveness in prostate cancer. We assessed these biomarkers
      in biopsy and radical prostatectomy specimens as predictors of biochemical
      relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically
      localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative
      (prostate specific antigen, biopsy Gleason score) and postoperative (pathological
      stage and margin status) variables, biopsy and radical prostatectomy biomarker
      immunohistochemistry were correlated with relapse. Univariate and multivariate
      statistical analyses identified significant predictors. RESULTS: Of the 76
      patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2,
      CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and
      57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy
      Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and
      negative predictive values for relapse. Relapse occurred in 13% of patients with
      normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed
      Gleason score and p53 to be independent preoperative predictors (p = 0.01 and
      0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients
      with Gleason scores 7 to 10 and 24% higher in those with aberrant p53.
      Significant postoperative predictors were bcl-2, p53, Gleason score and margin
      status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant
      biopsy p53 is associated with a significantly worse outcome after radical
      prostatectomy than normal p53, highlighting a potential clinical role for p53.
      Postoperative p53 and bcl-2 were significant predictors of outcome after radical
      prostatectomy.

PMID- 10081878
TI  - Retrovesical mass in men: pitfalls of differential diagnosis.
AB  - PURPOSE: We review the differential diagnosis and treatment of retrovesical
      masses in men. MATERIALS AND METHODS: During the last 8 years 21 male patients 3
      to 79 years old (mean age 47.1) presented with symptoms or signs of a
      retrovesical mass. Clinical features and diagnostic findings were reviewed, and
      related to surgical and histopathological findings. RESULTS: The retrovesical
      masses included prostatic utricle cyst in 3 cases, prostatic abscess in 1,
      seminal vesicle hydrops in 6, seminal vesicle cyst in 2, seminal vesicle empyema
      in 3, large ectopic ureterocele in 1, myxoid liposarcoma in 1, malignant fibrous
      histiocytoma in 1, fibrous fossa obturatoria cyst in 1, hemangiopericytoma in 1
      and leiomyosarcoma in 1. In 17 patients various symptoms were seen and in 4 the
      mass was incidentally detected. A mass was palpable on digital rectal examination
      in 16 cases and visible on sonography in 20. For a cystic mass medial location
      relative to the bladder neck was suggestive of prostatic abscess or utricle cyst,
      while lateral location was suggestive of seminal vesicle cyst/hydrops or empyema,
      ectopic ureter or ureterocele. In 6 patients diagnosis was established only by
      exploratory laparotomy and histopathological examination. CONCLUSIONS: Digital
      rectal examination and sonography reliably detect a retrovesical mass.
      Nevertheless, clinical signs and median or lateral location relative to the
      bladder neck on ultrasound are diagnostic only for cystic lesions. Computerized
      tomography and magnetic resonance imaging are useful for staging malignant
      tumors. However, needle or open biopsy is required in most cases to establish a
      histopathological diagnosis. Exploratory laparotomy and histopathological
      examination are the procedures of choice when other findings are equivocal.

PMID- 10081879
TI  - Urodynamic findings in adults with the tethered cord syndrome.
AB  - PURPOSE: We evaluated bladder function in adults with the tethered cord syndrome
      using multichannel urodynamics. MATERIALS AND METHODS: A total of 21 patients a
      mean 39.6 years old (range 20 to 62) with a tethered cord were evaluated. Of the
      patients 13 were diagnosed with a tethered cord as an adult and 8 had undergone
      previous spinal surgery. The tethered cord syndrome was diagnosed by magnetic
      resonance imaging in 20 patients and computerized tomography myelogram in 1. All
      patients underwent complete neurological and urological evaluation, including
      multichannel urodynamics. Needle electromyography and video urodynamics were
      performed in select cases. Microsurgical release of the tethered cord was
      performed in 19 patients and 2 refused surgery. Urodynamics were done before
      surgery in 16 of 19 patients and a median of 12.5 months (range 1 to 40) after
      surgery in 14. In addition, intraoperative urodynamic monitoring and nerve root
      stimulation were done in 14 patients to prevent nerve root injury at surgery.
      RESULTS: At presentation urgency (67%) and urge incontinence (50%) were the most
      common findings in 18 patients with urinary symptoms. Pretreatment urodynamics in
      18 of 21 patients revealed hyperreflexia in 13 (72%), external detrusor-sphincter
      dyssynergia in 4 (22%), decreased sensation in 4 (22%), decreased compliance in 3
      (17%) and hypocontractile detrusor in 2 (11%). Postoperative urodynamic findings
      were improved in 4 patients (29%) and unchanged in 10 (71%). Preoperative
      external detrusor-sphincter dyssynergia in 4 patients resolved postoperatively in
      3 and was unchanged in 1. Urinary symptoms were improved in 19% of patients (4),
      unchanged in 76% (16) and worse in 5% (1). To date 7 patients require
      anticholinergics, 4 require clean intermittent catheterization and 1 is taking an
      alpha-blocker. CONCLUSIONS: Adults with the tethered cord syndrome are less
      likely to have urodynamic or symptom improvement after cord release and most
      often present with irreversible findings which rarely become worse after surgery.
      These patients need to have careful and continuous followup, including urodynamic
      studies, due to possible re-tethering with time.

PMID- 10081880
TI  - Treatment results using a mixed fiber mesh in patients with grade IV cystocele.
AB  - PURPOSE: We determined the efficacy of a modification of the 4-corner bladder and
      bladder neck suspension procedure using mixed fiber mesh to correct grade IV
      cystocele. MATERIALS AND METHODS: We evaluated 15 women with a mean age of 67
      years who had severe anterior vaginal wall prolapse, of whom 3 had concurrent
      enterorectocele. Previously 5 patients had undergone repair of anterior vaginal
      wall prolapse and 2 had undergone procedures for stress urinary incontinence. In
      10 patients type II stress urinary incontinence was diagnosed with urethral
      hypermobility and abdominal leak point pressure greater than 90 cm. water. No
      patients with intrinsic sphincter deficiency were enrolled in the study. A mixed
      fiber mesh was positioned using a modification of the 4-corner bladder and
      bladder neck suspension technique. Patients with concurrent enterorectocele
      underwent simultaneous formal repair of the posterior descensus. RESULTS: All
      patients were available for postoperative pelvic examination at 3-month
      intervals. Mean followup was 23.4 months (range 18 to 39). Of the 15 women 13
      were continent (dry) at followup. No recurrent cystocele was evident, except in 1
      patient who presented with segmental posterior bladder prolapse. In 2 patients
      new onset enterorectocele developed 6 months after mesh implantation.
      CONCLUSIONS: Our study confirms that the addition of mesh to the classic 4-corner
      bladder base and neck suspension procedure effectively treats incontinence and
      cystocele. We recommend this method for cases in which traditional techniques
      have previously failed and when the quality of suspending tissue is poor or
      defective, as in connective tissue disease. However, the risk of worsening
      enterorectocele or its new onset must be considered.

PMID- 10081881
TI  - Magnetic resonance imaging detection of symptomatic noncommunicating
      intraurethral wall diverticula in women.
AB  - PURPOSE: We documented the merit of endorectal coil magnetic resonance imaging
      (MRI) for detecting intraurethral wall diverticula in women. MATERIALS AND
      METHODS: We report on 3 women with a long-standing history of urinary frequency,
      urgency and voiding dysfunction who had been treated unsuccessfully for other
      etiologies. RESULTS: MRI of the urethra revealed noncommunicating intraurethral
      wall diverticula, which were excised. CONCLUSIONS: Urethral MRI should be
      considered in women with lower urinary tract symptoms secondary to a suspected
      urethral pathology.

PMID- 10081882
TI  - Office based criteria for predicting type II stress incontinence without further
      evaluation studies.
AB  - PURPOSE: The 1996 Agency for Health Care Policy and Research Clinical Practice
      Guidelines for Urinary Incontinence suggested that surgery may be performed after
      basic evaluation without further testing in cases of uncomplicated nonrecurrent
      type II stress urinary incontinence. However, they failed to recommend explicit
      office based criteria to identify this condition without further invasive
      testing. We establish such criteria and test the efficacy. MATERIALS AND METHODS:
      Records of 101 women with urinary incontinence who underwent complete evaluation
      from June 1995 to September 1997 were reviewed. Basic evaluation consisted of
      medical history, physical/pelvic examination and the validated Medical,
      Epidemiologic and Social Aspects of Aging Urinary Incontinence Questionnaire,
      while further testing included cystourethroscopy, urodynamics and lateral stress
      cystogram. All cases diagnosed as pure type II stress urinary incontinence after
      basic and further testing were identified, and office based findings were
      characterized, which included medical history, questionnaire scores, vaginal
      speculum examination results and post-void residual urine volume. These criteria
      were applied in a blinded fashion to the initial group of 101 patients and then
      to a new group of 45 women with incontinence who recently underwent complete
      evaluation. RESULTS: Specificity and positive predictive value were 100% in both
      groups for nonsurgical cases, compared to 81 and 71% in the initial, and 75 and
      60% in the new group, respectively, for surgical cases. CONCLUSIONS: Our office
      based criteria are 100% specific for predicting pure type II stress urinary
      incontinence in women with no suspension surgery and, thus, have the potential of
      reducing the need for further invasive testing and consequently the cost of
      preoperative evaluation.

PMID- 10081883
TI  - Suprameatal transvaginal urethrolysis.
AB  - PURPOSE: We describe and assess a method of urethrolysis using a transvaginal
      suprameatal approach without lateral perforation of the urethropelvic ligament.
      MATERIALS AND METHODS: Between March 1993 and December 1997, 32 consecutive women
      32 to 79 years old underwent suprameatal transvaginal urethrolysis at 2
      institutions. In all cases anti-incontinence surgery was done previously,
      including a pubovaginal sling procedure in 12, Marshall-Marchetti-Krantz
      procedure in 8, Burch colposuspension in 6, modified Pereyra transvaginal
      urethropexy in 4, and Gittes suspension and anterior repair in 1 each. Of the 32
      patients 20 were in urinary retention and 12 had primarily urge and/or irritative
      voiding symptoms, or urge incontinence. In the patients in urinary retention
      average maximal detrusor pressure was 41.4 cm. water. In all cases physical
      examination, cystourethroscopy and video urodynamics were done before suprameatal
      transvaginal urethrolysis. Obstruction was defined as detrusor pressure greater
      than 20 cm. water at maximum urinary flow of less than 12 ml. per second.
      Urethral obstruction was presumed when examination revealed urethral angulation,
      tethering, narrowing or scarification. Impaired detrusor contractility was
      diagnosed when detrusor pressure at maximum urinary flow was less than 20 cm.
      water at maximum urinary flow of less than 12 ml. per second. RESULTS: After
      suprameatal transvaginal urethrolysis 13 of the 20 women (65%) in urinary
      retention voided well and in 8 of the 12 (67%) with urgency symptoms resolved.
      Postoperative stress urinary incontinence developed in only 1 case. CONCLUSIONS:
      The success rate of suprameatal transvaginal urethrolysis to treat urinary
      obstruction associated with anti-incontinence procedures compares favorably to
      that of other described alternative approaches. The success rate in patients with
      definite urodynamic criteria for obstruction was not significantly better than in
      those who underwent suprameatal transvaginal urethrolysis based on physical
      examination and clinical judgment. Preoperative maximal urinary flow rate was
      associated with operative success (p = 0.018), while preoperative post-void
      residual urine and maximum detrusor pressure failed to reveal a difference
      between operative success and failure.

PMID- 10081884
TI  - Primary aldosteronism due to aldosterone producing adenoma without hypertension.

PMID- 10081885
TI  - Air as a contrast agent.

PMID- 10081886
TI  - Complete infundibular obliteration following percutaneous nephrolithotomy.

PMID- 10081887
TI  - Ureteral obstruction secondary to posterior spinal fixation rods.

PMID- 10081888
TI  - Lymphoepithelioma-like carcinoma of the ureter.

PMID- 10081889
TI  - Urothelial striations in a patient with transitional cell carcinoma in situ
      involving the ureter.

PMID- 10081890
TI  - Splenosis mimicking transitional cell carcinoma.

PMID- 10081891
TI  - Urological needs assessment for primary care practice: implications for
      undergraduate medical education.
AB  - PURPOSE: The majority of graduating medical students will become primary care
      physicians. We discuss what urological topics primary care physicians need to
      know, proficiency in urological skills of primary care physicians and
      undergraduate urological curriculum recommendations that would serve the needs of
      primary care physicians. MATERIALS AND METHODS: A written survey instrument was
      mailed to all 452 family practice residency directors in the United States.
      Subjects rated how well family practice physicians need to know urological topics
      and how proficient they must be in urological skills. RESULTS: A total of 329
      responses were received (response rate 73%). Respondents indicated that they need
      to know urinary tract infection, sexually transmitted disease, epididymitis,
      benign prostatic hyperplasia diagnosis, hematuria and erectile dysfunction
      diagnosis very well. They indicated a greater need to know diagnostics than
      staging or management of prostate, bladder, renal or testis cancer (p <0.05).
      Among diagnostics respondents indicated that generalists should be highly
      proficient in urinalysis interpretation. Proficiency was ranked greater for
      interpretations of semen analysis than excretory urogram, abdominal computerized
      tomography or magnetic resonance imaging, or renal ultrasound (p <0.05).
      Proficiency in catheter insertion and circumcision was ranked highly, and
      vasectomy was ranked moderately. CONCLUSIONS: Primary care physicians need to
      know and be proficient in many urological topics and skills. They need to know
      diagnostics better than staging and management information, and urological
      infectious topics better than urological cancers. They need to be proficient in
      physical examination, urinalysis interpretation, catheter insertion, circumcision
      and vasectomy. Undergraduate medical education should reflect these needs.

PMID- 10081892
TI  - Re: The use of bladder for total transplant ureteral reconstruction.

PMID- 10081893
TI  - Re: Tubularized incised plate hypospadias repair for proximal hypospadias.

PMID- 10081894
TI  - Re: Radical prostatectomy for prostate cancer: the perineal approach increases
      the risk of surgically induced positive margins and capsular incisions.

PMID- 10081895
TI  - Supranormal renographic differential renal function in congenital hydronephrosis:
      fact, not artifact.
AB  - PURPOSE: Children with unilateral hydronephrosis, who had been prospectively
      examined with diethylenetriaminepentaacetic acid (DTPA) and dimercapto-succinic
      acid (DMSA) renography, were evaluated to determine whether supranormal
      renographic differential renal function exists. MATERIALS AND METHODS: A total of
      54 children with congenital single system hydronephrosis underwent abdominal
      ultrasound, voiding cystourethrogram, and DTPA and DMSA renal scans. None had
      abnormalities of the bladder or contralateral kidney. Differential renal function
      greater than 55% was defined as supranormal. RESULTS: Of the 54 patients 15 (28%)
      with a median age of 4 months (range 0.5 to 66) were identified with supranormal
      renographic renal function on either DTPA or DMSA. Supranormal renographic renal
      function was detected by DMSA in 9 cases (mean 57+/-2%), DTPA in 8 (mean 58+/-2%)
      and both in 2 (mean 57+/-2%). Average function demonstrated in the 15 patients
      was 55+/-3% (range 51 to 62) with DMSA which was not different from that found
      with DTPA (mean 55+/-4%, range 46 to 61%). The kidneys with supranormal
      renographic renal function were significantly larger than hydronephrotic controls
      according to longitudinal parenchymal area on DMSA. Mean followup was 20 months
      for 13 patients, with 8 of 13 (62%) undergoing pyeloplasty. Followup DTPA renal
      scans available in 9 children revealed persistent supranormal function in 6,
      despite pyeloplasty in 3. CONCLUSIONS: Supranormal renographic differential renal
      function does exist in congenital hydronephrosis and when found the kidneys are
      consistently enlarged. The position of supranormal renographic renal function in
      the management algorithm of hydronephrosis remains to be elucidated as it does
      not appear to be a benign prognostic factor.

PMID- 10081896
TI  - Extraosseous metaplasia of the renal pelvis in a child.

PMID- 10081897
TI  - Single system ureteral ectopia in boys associated with bladder outlet
      obstruction.
AB  - PURPOSE: Ureteral ectopia is frequently associated with dysplasia of the
      associated renal segment in girls with ureteral duplication. However, single
      system ureteral ectopia is an uncommon anomaly more frequently noted in boys. We
      report on 6 boys with single system ureteral ectopia into the prostatic urethra
      above the verumontanum, who presented with radiological and clinical findings of
      bladder outlet obstruction. MATERIALS AND METHODS: Antenatal ultrasound in 3 boys
      demonstrated renal abnormalities and postnatal studies suggested the diagnosis of
      posterior urethral valve obstruction. Older boys presented with symptoms
      suggestive of bladder outlet obstruction. RESULTS: An ectopic ureter inserting
      into the prostatic urethra was noted in all 6 boys. The distal ureter was dilated
      elevating the bladder neck causing outlet obstruction. Surgical management
      consisted of nephrectomy and transurethral endoscopic incision of the distal
      ureter or nephroureterectomy with reconstruction of the prostatic urethra. In 2
      younger boys voiding dysfunction with inability to empty developed. CONCLUSIONS:
      Single system ectopic ureters in boys may present with symptomatic and
      radiological findings resembling posterior urethral valves. Surgical treatment
      should include nephroureterectomy with reconstruction of the hypoplastic
      prostate. Some patients may have later voiding dysfunction.

PMID- 10081898
TI  - Postneonatal circumcision with local anesthesia: a cost-effective alternative.
AB  - PURPOSE: Despite the controversy regarding the need for routine neonatal
      circumcision, most boys in the United States are circumcised. Physicians are
      commonly asked to perform circumcision after the neonatal period and are often
      unaware of the cost factors related to the timing and location of postneonatal
      circumcision. MATERIALS AND METHODS: We describe the medical and financial
      advantages of postneonatal circumcision with local versus general anesthesia.
      RESULTS: During a 30-month period 245 boys 6 months to 15 years old underwent
      circumcision under general anesthesia in the operating room. Hospital charges
      (facility and equipment) averaged $1,555 and anesthesia charges averaged $250.
      Therefore, the average cost for circumcision in the operating room was $1,805.
      During the same time period 287 infants 3 days to 9 months old (20% older than 3
      months) underwent circumcision under local anesthesia in an office setting. The
      facility and equipment charge for these office procedures averaged $196. Overall,
      approximately $461,783 were saved in this 30-month period ($184,713 annually) by
      performing circumcision with local anesthesia in an office setting rather then in
      the operating room with general anesthesia. There was no significant difference
      in complication rates between the local and general anesthesia groups (1.4 versus
      1.6%). CONCLUSIONS: Circumcision with local anesthesia can be performed easily
      and safely during the first several months of life and has many advantages.
      Parents prefer this method because it is more convenient and eliminates the risk
      of general anesthesia. The enormous cost savings using local as opposed to
      general anesthesia should prompt a reexamination of the location and timing of
      postneonatal circumcision.

PMID- 10081899
TI  - Congenital dorsal penile curvature: a potential problem of the long phallus.
AB  - PURPOSE: We report the results of surgical correction of severe congenital dorsal
      penile curvature associated with a long slender phallus. MATERIALS AND METHODS:
      In the last 7 years we treated 16 boys with a mean age of 2 years 10 months who
      had severe dorsal penile curvature. The series included 5 patients with
      megameatus variant hypospadias and a full foreskin, 3 who presented with
      hypospadias and 8 who were referred when dorsal penile curvature was noticed by
      the family or primary physician. Mean penile length was 6.5 cm. without
      stretching. In each case length was greater than 2 standard deviations above the
      mean for patient age. Penile circumference decreased from a mean of 4.2 cm. at
      the base of the shaft to 4.1 cm. at the mid shaft and 3.7 cm. at the corona.
      Penile circumference was generally normal for patient age until corrected for
      length, when it was revealed to be small. Surgical correction of severe curvature
      was performed in 14 patients, while 2 who presented as newborns had remarkable
      spontaneous improvement in the first year of life. In each case curvature was due
      to corporeal disproportion. RESULTS: All patients have erections postoperatively.
      There has been no residual or recurrent curvature and cosmetic results are good.
      CONCLUSIONS: Congenital dorsal penile curvature is a potential problem of the
      long phallus. In severe cases surgical repair improves the appearance of the
      penis but it must also address the problem of corporeal disproportion.

PMID- 10081900
TI  - Gender assignment and the pediatric urologist.

PMID- 10081901
TI  - Lewis antigen mediated adhesion of freshly removed human bladder tumors to E
      selectin.
AB  - PURPOSE: Twenty fresh surgical specimens of human bladder tumors were tested for
      their ability to adhere to recombinant P and E-selectin. The adhesion was
      correlated to immunological detection of carbohydrate structures. MATERIALS AND
      METHODS: A static titertray assay with immobilized selectins and appropriate
      controls was used for bladder tumor cell adhesion. On the same tumors expression
      of carbohydrate structures was examined by immunohistochemistry and Western
      blotting. RESULTS: No tumor bound to P-selectin. Nine tumors showed a high number
      of cells binding to E-selectin, 5 showed intermediate binding, and 6 showed only
      rare binding. The specificity of the binding was verified by inhibition with
      EDTA, by blocking antibodies to E-selectin, and by an acrylamide based sLe(x)
      (Galbeta1-4 [Fucalpha1-3]GlcNAc-) polymer. The binding was significantly more
      frequent (p <0.045) in superficial tumors than in invasive tumors. The binding
      property was correlated to the detection of carbohydrate structures in Western
      blots and tissue sections of the same tumors, using six different monoclonal
      antibodies: anti-sLe(a), anti-sLe(x), anti-Le(a), anti-Le(x) (two different
      clones) and anti-Le(b). Most blot-stainings were smeared indicating a mucin-type
      carrier molecule, but 115, 55 and 40 kDa bands carrying Le(a) and/or Le(b)
      epitopes were present in all tumors that bound. The Le(a) structure, as detected
      by blotting, was the only structure necessary for binding in the center of the
      wells (p <0.001), and was correlated to number of bound cells (p <0.006). A
      weaker correlation was found between Le(b) and number of bound cells (p <0.032),
      whereas it was remarkable that no correlation was found with Le(x) or sLe(x).
      Immunohistological staining of Le(a) on cell membranes correlated with frequent
      binding (p <0.003), whereas no correlation was found to secretor and Lewis
      genotypes. CONCLUSIONS: These data on clinical specimens indicate that Lewis
      antigen mediated E-selectin adhesion may play a role in the human bladder cancer
      disease.

PMID- 10081902
TI  - Relative roles of cyclooxygenase and nitric oxide synthase pathways in ischemia
      induced increased contraction of cavernosal smooth muscle.
AB  - PURPOSE: To study the mechanism of chronic ischemia-induced increased cavernosal
      smooth muscle contraction in an animal model of vasculogenic erectile
      dysfunction. MATERIALS AND METHODS: New Zealand White rabbits were divided into
      control (n = 6, fed with a regular diet), hypercholesterolemic (n = 9, fed with a
      diet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 10,
      underwent balloon de-endothelialization of iliac arteries and received a diet
      containing 0.5% cholesterol) groups. After 16 weeks, the relationship between
      iliac artery blood flow and cavernosal smooth muscle contraction was studied. The
      roles of cyclooxygenase and nitric oxide (NO) pathways in chronic ischemia
      induced increased smooth muscle contraction were also examined. RESULTS: Iliac
      artery blood flow in the CCI group was significantly reduced compared with the
      control and hypercholesterolemic groups. Hypercholesterolemia alone did not
      affect cavernosal smooth muscle contraction. Atherosclerosis-induced chronic
      cavernosal arterial insufficiency did not affect contraction to norepinephrine
      while causing a significant increase in electrical field stimulation-induced
      neurogenic contraction. Inhibition of the cyclooxygenase pathway by indomethacin
      decreased electrical field stimulation-induced contraction in all animals but
      failed to normalize the differences between CCI and control groups. In the
      presence of indomethacin, L-arginine decreased electrical field stimulation
      induced contraction in the control and hypercholesterolemic groups but not in the
      CCI group. In the presence of indomethacin, treatment with nitric oxide synthase
      (NOS) inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), increased electrical field
      stimulation-induced contraction in all groups. This effect of L-NMMA on smooth
      muscle contraction was significantly greater in the control and
      hypercholesterolemic groups compared with the CCI group. After tissue treatment
      with L-NMMA, the magnitude of contraction in cavernosal tissue from control and
      hypercholesterolemic groups was similar to those observed in the CCI group.
      CONCLUSIONS: Mechanism of chronic ischemia-induced increased cavernosal smooth
      muscle contraction involves increased output of constrictor eicosanoids and
      impairment of the inhibitory influence of NO pathway in cavernosal tissue.

PMID- 10081903
TI  - Characterization of a stromal cell model of the human benign and malignant
      prostate from explant culture.
AB  - PURPOSE: There is a lack of suitable in vitro models for the human prostate. To
      study stromal-epithelial interactions, we established stromal cells in cultures
      from benign and malignant prostate tissue that resemble more closely the in vivo
      conditions of the human prostate. MATERIALS AND METHODS: Stromal cells were
      obtained from explant primary culture, established in DU145 cell conditioned
      medium and maintained in RPMI-fetal bovine serum (FBS) supplemented with insulin,
      transferrin and selenium (ITS). Proliferation studies to compare different media
      were performed using a 3[H]thymidine assay. Stromal cells were characterized by
      immunocytochemistry using epithelial and mesenchymal markers. Morphology was
      evaluated by electron microscopy, light and phase-contrast microscopy. Androgen
      receptor (AR) mRNA expression was measured by polymerase-chain-reaction (PCR).
      The response to different concentrations of dihydrotestosterone (DHT) and the
      antihormones flutamide and hydroxyflutamide was tested by 3[H] thymidine assay.
      RESULTS: Microscopic evaluation revealed typical stromal morphology with
      elongated cell shapes, cilia, collagen and microfilaments. Immunocytochemical
      characterization revealed typical fibroblastic and smooth muscle differentiation.
      ITS supplemented in RPMI-FBS showed the best growth stimulation compared with
      other serum-free media (p <0.05) and became our basal medium. The presence of
      DU145 cell conditioned medium in this basal medium showed a significant increase
      in cell proliferation in stromal cells. Stromal cells maintained AR mRNA
      expression and significant DHT dose dependent growth stimulation in up to 10
      passages. Both the antiandrogens flutamide and hydroxyflutamide counteracted the
      DHT effect (p <0.05). CONCLUSIONS: This stromal cell model maintains many
      cellular and functional properties of the human prostate, which may enable us to
      study growth factor modulation, drug and hormone metabolism in stromal-epithelial
      interaction with emphasis on the pathogenesis of BPH and prostate cancer.

PMID- 10081904
TI  - Molecular detection of prostate cells in ejaculate and urethral washings in men
      with suspected prostate cancer.
AB  - PURPOSE: To determine whether prostatic cells were normally present in ejaculate
      and if the sensitivity and specificity of the detection of malignant prostate
      cells in ejaculate and urethral washings from men with suspected prostate cancer
      could be improved using the more sensitive molecular technique of reverse
      transcriptase-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS: RT-PCR
      for prostate-specific antigen (PSA), prostate-specific membrane antigen (PSM) and
      Apoliprotein D (3 putative prostate-specific and/or cancer-specific markers) was
      performed on RNA extracts of ejaculate (80) and urethral washings (52) from 77
      men with suspected prostate cancer and 12 young controls (<30 years of age) and
      urines from 5 men who had radical prostatectomies and 10 women. RESULTS: PSA, PSM
      and Apolipoprotein D expression was detected in ejaculates and urethral washings
      from both patient and control groups. No differences were observed in the results
      obtained for 58 men with suspected or 19 men with confirmed prostate cancer or
      the 18 vasectomized men within the patient group. Urines from the 5 men who had
      radical prostatectomies and 10 women were all negative for PSA, but PSM was
      detected in 2 female urines and in 3 radical prostatectomy samples. As few as 10
      LNCaP prostate tumor cells could be detected by PSA RT-PCR when added to female
      urine. CONCLUSION: We have established a sensitive method of detecting prostatic
      cells in ejaculate and urethral washings and shown that PSA RT-PCR is a reliable
      indicator of prostate cells in these samples. However, RT-PCR for PSA, PSM and
      Apoliprotein D were not useful for discriminating malignant from non-malignant
      prostate cells.

PMID- 10081905
TI  - The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary
      report in a canine model.
AB  - PURPOSE: The use of mesh bioprosthesis during inguinal herniorrhaphy is now
      considered routine. To our knowledge, no studies have examined the effects of
      mesh induced fibrosis on the structure and function of the adjacent spermatic
      cord. We present our experience in a canine model. MATERIALS AND METHODS:
      Unilateral inguinal hernia defects were created in 12 male beagle dogs. Half were
      repaired using Marlex mesh and half using a classic Shouldice technique. The
      inguinal anatomy was then re-examined at 6 and 12 months. Testicular temperature
      and volume, peripheral and testicular vein testosterone levels, testicular blood
      flow, vasography, testicular and cord histology, and sperm motility/morphology
      were recorded. Groups were compared with each other as well as to the non
      operated (control) side. RESULTS: Although post-operative testicular volumes from
      both the mesh and Shouldice groups were similar to controls (p >0.05), there was
      a downward trend after mesh repair (17.8 cc pre versus 12.6 cc post) but this did
      not reach statistical significance (p = 0.17). Testicular temperatures and blood
      flow did not differ between experimental groups and controls. While testicular
      vein testosterone levels were significantly higher than peripheral venous levels
      after Shouldice repair, this difference was lost after mesh repair. Contralateral
      (control) testicular vein testosterone levels were higher in animals repaired
      with mesh than by an anatomic Shouldice repair (p <0.05). There was a significant
      decrease in cross sectional vasal luminal diameter in both the anatomic and mesh
      repair groups versus their respective contralateral controls (p <0.05). This was
      correlated with a marked foreign body reaction to the mesh in the soft tissues
      surrounding the vas in spermatic cords exposed to Marlex. All vasograms
      demonstrated patency. Gross pathology was abnormal in 3/6 dogs with mesh repair
      (2 hydroceles and 1 ischemic testis) and 0/6 animals after Shouldice repair. A
      traumatic neuroma was identified in the mesh group. Sperm morphology and motility
      did not differ between the two groups. CONCLUSIONS: Half of the testicles had
      gross abnormalities after mesh repair versus none in the control and Shouldice
      dogs. Although all vasograms were patent, vasal luminal size was significantly
      decreased with a marked soft tissue foreign body reaction identified after mesh
      repair. A traumatic neuroma was identified suggesting nerve entrapment in the
      fibrotic mesh reaction, which may account for post-operative pain seen in some
      patients. Marlex mesh may adversely affect spermatic cord structure and function
      and further work is required to fully elucidate its effects.

PMID- 10081906
TI  - New alpha1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher
      affinity for human prostates than arteries.
AB  - PURPOSE: We compared the affinities of a new alpha1-adrenoceptor (AR) antagonist,
      JTH-601 with those of several alpha1-AR antagonists in human prostates and
      arteries. RESULTS: In the functional study, noradrenaline produced concentration
      dependent contractions in human prostates and mesenteric arteries. The pA2/pKB
      values for the antagonists in the human prostate were 9.78 for tamsulosin, 8.84
      for JTH-601, 8.39 for WB4101, 8.23 for prazosin, 8.12 for JTH-601-G1 (a main
      metabolite of JTH-601 in human) and 6.57 for BMY7378. Compared these affinities
      with those in the mesenteric artery, only JTH-601 and JTH-601-G1 exhibited unique
      uroselectivity, showing 10- to 20-fold higher affinity for the human prostate
      than for mesenteric artery. The affinity profile of these antagonists suggested
      that the noradrenaline-induced contractions in the human prostate and the
      mesenteric artery were mediated by the alpha1L-AR and alpha1B-AR, respectively.
      In the competition binding study, the pharmacological profiles of the antagonists
      against [3H]-prazosin were examined in the human prostate and aorta. The
      resulting pKi values for JTH-601 and JTH-601-G1 were also approximately 10- to 20
      fold higher for the human prostate than for the human aorta. CONCLUSION: These
      results have suggested that JTH-601 and JTH-601-G1 are unique uroselective alpha1
      AR antagonists that show higher affinity for the human prostate than for the
      human arteries.

PMID- 10081907
TI  - Somatic mutations at the SRD5A2 locus encoding prostatic steroid 5alpha-reductase
      during prostate cancer progression.
AB  - Prostate cancer is a serious public health problem in many industrialized
      countries. Androgens appear to play a critical role in its etiology.
      Specifically, the active androgen in the prostate, dihydrotestosterone (DHT)
      which is synthesized by the enzyme steroid 5alpha-reductase from testosterone
      (T), acts as a mitogen. Hence androgen-deprivation is commonly used during
      prostate cancer therapy. Two isozymes for steroid 5alpha-reductase have been
      reported. The type II enzyme is prostate-specific and encoded by the SRD5A2 gene.
      We have investigated a polymorphic (TA)n dinucleotide repeat in the 3' UTR
      (untranslated region) of the SRD5A2 gene in 30 matched samples of constitutional
      ("germline") DNA from peripheral blood lymphocytes and microdissected, pure tumor
      DNA. We report here 8 LOH (loss of heterozygosity) events and 9 cases of
      microsatellite instability at this marker. Therefore, almost 57% of the samples
      examined showed evidence of somatic mutations at the 3' UTR of the SRD5A2 locus.
      Our data suggest that the SRD5A2 gene may be involved in prostate cancer
      progression and that this may have relevance for treatment of the disease.

PMID- 10081908
TI  - Role of matrix metalloproteinase-9 in the basement membrane destruction of
      superficial urothelial carcinomas.
AB  - PURPOSE: This study was conducted to clarify which matrix metalloproteinases
      (MMPs) play a key role in destruction of the underlying basement membrane (BM) of
      superficial urothelial carcinomas. Urine concentrations of MMP-9 and tissue
      inhibitors of matrix metalloproteinase-1 (TIMP-1) were also measured. MATERIALS
      AND METHODS: Overexpression of MMP-1, MMP-2 and MMP-9 was analyzed
      immunohistochemically in 60 patients with transitional cell carcinomas of the
      urothelium (41 were pTa or pis, 19 were pT1-4), and compared them with type IV
      collagen expression in tumor BM. In 33 of them, urine concentrations of MMP-9 and
      TIMP-1 were measured by one-step sandwich enzyme immunoassay. RESULTS: Positive
      expression of MMP-1, MMP-2 and MMP-9 was found in 53%, 17%, and 65% of tumors,
      respectively. Only MMP-9 expression rates were increased with grades and stages
      (p = 0.03). In pTa and pis tumors, type IV collagen expression was reduced in 17
      of 26 (65.4%), and it was associated with positive MMP-9 expression (p = 0.0283).
      MMP-9 was detected in all urine samples of urothelial cancer patients, while
      urine TIMP-1 was detectable in 18 of 33 patients. In 16 healthy volunteers, both
      of them were below detectable levels. Balance between urinary MMP-9 and TIMP-1
      were particularly kept in superficial urothelial carcinomas with intact tumor BM.
      Tumor BM status, however, was not associated with urinary MMP-9 or TIMP-1 levels.
      CONCLUSIONS: These results suggest that MMP-9 plays a key role in the invasion
      step of superficial urothelial carcinomas. Detection of urinary MMP-9 may become
      a new, non-invasive mean for the diagnosis of urothelial carcinomas.

PMID- 10081909
TI  - Reduction of integrin beta4 and enhanced migration on laminin in association with
      intraepithelial spreading of urinary bladder carcinomas.
AB  - PURPOSE: The aim of the present study was to investigate the biological and
      molecular basis of intraepithelial spreading (IES) of carcinomas in situ (CIS) of
      the urinary bladder, which were considered to be precursors of nodular invasive
      carcinomas. MATERIALS AND METHODS: The propensity for IES of human transitional
      carcinoma cells was examined by inoculation into murine renal pelvis and urinary
      bladder, and the biological character of the cells with a high propensity for IES
      was explored in vitro. RESULTS: Three of 6 cell lines exhibited a high propensity
      for IES. When cultured on laminin, these IES cells scattered, whereas 3 non-IES
      cells and 2 immortalized transitional epithelial cells did not. IES cells showed
      strong adhesiveness, haptotaxis and enhanced migration on laminin compared with
      both non-IES and immortalized transitional epithelial cells. In IES cells,
      expression of the integrin beta4 subunit was markedly reduced and the integrin
      alpha6beta1 complex was predominant compared with the integrin alpha6beta4
      complex. Transfection of IES cells with integrin beta4 subunit cDNA inhibited
      their ability to migrate on laminin and their propensity for IES. In addition,
      expression of the integrin beta4 subunit was reduced in surgically resected
      specimens of CIS of the urinary bladder. CONCLUSION: The results indicate that a
      reduction in integrin beta4 plays a role in IES of CIS of the urinary bladder
      through enhanced migration on laminin.

PMID- 10081910
TI  - Altered NGF regulation may link a genetic predisposition for hypertension with
      hyperactive voiding.
AB  - PURPOSE: Hyperactive voiding and elevated smooth muscle NGF output are traits of
      the spontaneously hypertensive rat (SHR). Elevated target-derived NGF is
      associated with hypertension and hyperactive voiding in SHRs. In the present
      study, we tested for possible genetic links between hypertension, hyperactive
      voiding and augmented bladder smooth muscle cell (BSMC) NGF secretion. MATERIALS
      AND METHODS: We crossed SHRs with WKYs to produce a gene segregating F2
      population. We measured F2 mean arterial blood pressure (BP) and six-hour voiding
      frequency. BSMCs were cultured from 'Low BP F2s' (95+/-2) and 'High BP F2s'
      (141+/-3 mm. Hg) and conditioned medium tested for NGF with a two-site ELISA. The
      NGF regulators isoproterenol, platelet-derived growth factor (PDGF) and phorbol
      12-myristate-13-acetate were tested in F2 BSMC cultures. RESULTS: A positive
      correlation (r = 0.75) between blood pressure and voiding frequency existed in
      this F2 population. As BP rose voiding frequency increased and volume per void
      decreased such that there were no significant changes in total urine voided (Low
      BP F2s: 1.0+/-0.5; High BP F2s: 6.2+/-0.5 voids/6 hours). Low BP F2s (2.0+/-0.2)
      secreted NGF at a higher basal rate than High BP F2s (0.7+/-0.1 fg NGF/hr/100
      cells). However, High BP F2s (1,620 and 3,850) were oversensitive to
      isoproterenol and PDGF-induced increases in NGF output, compared with Low BP F2s
      (219 and 1,282% control, respectively). CONCLUSIONS: Elevated tissue NGF due to a
      hypersensitivity to NGF regulating stimuli, rather than alterations in basal NGF,
      may genetically link hypertension and hyperactive voiding.

PMID- 10081911
TI  - Identification of an activin-follistatin growth modulatory system in the human
      prostate: secretion and biological activity in primary cultures of prostatic
      epithelial cells.
AB  - PURPOSE: To determine if the activin/follistatin system is present in human
      prostate tissue and primary cultures of prostatic epithelium and if these growth
      factors play a role in the control of epithelial cell growth. MATERIALS AND
      METHODS: Cells derived directly from human prostates were studied to determine:
      a) if they secrete activin and follistatin, and b) if they are growth inhibited
      by activin. Primary cell cultures were established from tissues removed from 13
      unselected prostate carcinoma patients in order to examine the secretion of
      activin and follistatin and test the effects of these proteins on cell
      proliferation. RESULTS: Both primary explant cells and epithelial cells isolated
      and sub-cultured from explant cultures secreted activin A and follistatin.
      Treatment of cultured cells with recombinant human activin A resulted in a dose
      dependent inhibition of thymidine incorporation, with an IC50 of 0.22 nM.
      Recombinant follistatin neutralized the inhibitory effects of activin A on cell
      proliferation whilst adding follistatin alone enhanced thymidine incorporation,
      suggesting a similar neutralizing effect on the endogenous activin produced by
      these cells. CONCLUSION: These results demonstrate that cells derived from human
      prostate tissue secrete activin and follistatin and, as observed in human
      prostate cancer cell lines, activin inhibited the growth of prostatic epithelial
      cells. Also consistent with our earlier studies of prostate cancer cell lines,
      the biological activity of activin was neutralized by follistatin. These
      observations support the hypothesis that the activin/follistatin system plays an
      important role in the local regulation of human prostate cell growth.

PMID- 10081912
TI  - Dimethyl sulfoxide increases latency of anoxic terminal negativity in hippocampal
      slices of guinea pig in vitro.
AB  - Dimethyl sulfoxide (DMSO), which is widely used as a solvent for a variety of
      drugs, was used in the present study to investigate its ability to increase the
      hypoxic tolerance of brain tissue in vitro. DC-potentials and evoked potentials
      (EP, Schaffer collateral stimulation) were recorded in the CA1 region of
      hippocampal slices from adult guinea pigs. The latencies of the negative DC
      potential shift (anoxic terminal negativity, ATN) after onset of hypoxia (95% N2,
      5% CO2) were determined during superfusion with artificial cerebrospinal fluid
      (aCSF) or DMSO 0.4% dissolved in aCSF, respectively. The latencies of ATN were
      increased by DMSO application from 7.5+/-0.9 min (mean +/- SEM) under control
      conditions (n = 38) to 11.1+/-1.3 min with DMSO (n = 22, P < 0.01). These results
      demonstrate a neuroprotective effect of DMSO.

PMID- 10081913
TI  - Different effect of high doses of naloxone on spinal reflexes in normal subjects
      and chronic paraplegic patients.
AB  - There is still controversy over the effects of naloxone on spinal reflexes in
      view of the fact that both facilitatory and inhibitory activities have been
      observed. Dosage, supraspinal influences and interactions with different opiate
      receptors may account for the different findings. We investigated the effect of
      placebo (saline) and high doses of naloxone (1.66 mg/kg) on the monosynaptic (H
      reflex) and nociceptive polysynaptic reflex (RIII reflex) in five normal subjects
      and three chronic paraplegic subjects. Following the administration of naloxone,
      there were no changes in the RIII reflex threshold in either group. By contrast,
      there was a marked facilitation of the H reflex amplitude in the normal subjects,
      but not in the spinal cord-injured subjects after treatment with naloxone. Saline
      induced no changes in the RIII reflex threshold or the H reflex amplitude in
      either of the two groups. Our data suggest that under normal conditions the
      opiatergic modulation of the nociceptive reflex is not functionally active
      whereas the tonic inhibitory modulation of the monosynaptic reflex is mediated by
      descending pathways.

PMID- 10081914
TI  - Nitric oxide regenerates the normal colonic peristaltic activity in mdx
      dystrophic mouse.
AB  - We demonstrated in vitro that the colonic peristaltic activity is modified in
      dystrophin-deficient mdx mouse indicating a defect in the enteric nervous system
      (ENS). Since nitric oxide (NO) has been proposed as a putative inhibitory
      mediator of ENS, here we have examined the effects of both L-Arginine (L-Arg) and
      Nomega-nitro-L-arginine methyl ester (L-NAME) on the peristaltic activity of mdx
      mouse distal colon. The motor pattern of colonic segment showed irregular
      peristaltic waves. L-Arg (10(-7) - 10(-5) M) induced the peristaltic activity to
      slow down. At a concentration of 10(-5) M, L-Arg produced hypomotility,
      characterised by a decrease in amplitude, frequency and ejected fluid volume.
      Conversely, L-NAME elicited hypermotility, this effect being reversed once again
      by the subsequent addition of L-Arg. Interestingly the addition of 10(-5) M L-Arg
      to the organ bath led to the normal progression, in an oral to aboral direction,
      of 90% of the peristaltic waves. This last result strongly suggests that
      exogenous application of L-Arg restores the integrative circuits of the ENS
      responsible for programming and co-ordinating peristaltic activity in the distal
      colon of mdx mouse.

PMID- 10081915
TI  - Discrimination learning of amplitude modulated tones in Mongolian gerbils.
AB  - Discrimination learning of 100% sinusoidal amplitude modulated tones (AM) was
      investigated in adult Mongolian gerbils using a footshock motivated shuttle box
      avoidance go/no go paradigm. AM stimuli to be discriminated had identical carrier
      frequency (2 kHz) but differed in modulation frequency (fm) by one octave. Six
      groups of gerbils were trained to discriminate AM-pairs with fm ranging from 10
      to 640 Hz. Learning proceeded faster and discrimination performance was slightly
      better for low fm, up to 80 Hz, than for high fm, above 80 Hz. These results may
      be related to cortical AM encoding (Schulze, H. and Langner, G., J. Comp.
      Physiol. A, 181 (1997) 651-663), which is temporal for low fm (synchrony code)
      and spatial for high fm (rate-place code). This may implicate different neuronal
      learning strategies or distinct behavioral meanings influencing the
      discrimination training.

PMID- 10081916
TI  - Evidence for up-regulation of brain-derived neurotrophic factor mRNA by soy
      phytoestrogens in the frontal cortex of retired breeder female rats.
AB  - In this study, we examined the effects of oral micronized estradiol and soy
      phytoestrogens on the mRNA levels of brain-derived neurotrophic factor (BDNF) in
      the frontal cortex of ovariectomized retired breeder female rats. Fifteen
      ovariectomized rats were randomized into three groups and fed either a soy-free
      control diet (OVX), a control diet with added soybean estrogens (SBE), or a
      control diet with added estradiol (E2) for 8 weeks. Frontal cortex samples were
      collected for RNA isolation. Northern and Phosphorlmager analyses were used to
      determine the relative levels of BDNF mRNA. Both estradiol and soy phytoestrogens
      significantly increased the mRNA levels of BDNF compared to ovariectomized
      controls, suggesting that soy phytoestrogens may act as estrogen agonists in
      regulating BDNF mRNA in the frontal cortex of retired breeder female rats.

PMID- 10081917
TI  - Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats.
AB  - The present study was designed to investigate the role of manganese (Mn) as an
      antioxidant element. In vitro experiments have been conducted to evaluate the
      ability of Mn in scavenging oxygen free radicals. Superoxide (O*-) and hydroxyl
      (OH*-) radicals were generated in vitro by using xanthine and xanthine oxidase
      system and fenton reactions respectively. Different concentrations of Mn (II) and
      Mn (III) were used in the reaction mixture to evaluate free radical scavenging
      ability of Mn. The results indicated that Mn scavenged superoxide radicals at
      nanomolar concentrations whereas hydroxyl radicals were scavenged at micromolar
      concentrations. In addition, Mn-superoxide dismutase (SOD) activity was measured
      in different regions of brain in adult male rats treated with MnCl2. The results
      showed that Mn-SOD activity increased in Mn treated animals. Therefore, the data
      support the hypothesis that Mn is one of the essential elements which can protect
      against oxidative damage, however, at higher concentrations Mn can be neurotoxic
      by generating the free radicals.

PMID- 10081918
TI  - S-100beta protein is upregulated in astrocytes and motor neurons in the spinal
      cord of patients with amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by progressive motor neuron loss and astrogliosis. We studied the
      immunohistochemical expression of S-100beta, a calcium-binding protein with both
      neurotrophic and neurotoxic activities, in the spinal cord of patients with ALS.
      Adjacent sections were processed with an in situ end-labeling technique for the
      demonstration of apoptosis-related DNA fragmentation. In controls, low expression
      of S-100beta was found in astrocytes but not motor neurons. Compared to controls,
      S-100beta was overexpressed in ALS. Most stained cells were reactive astrocytes,
      but a minority of motor neurons was also labeled. Neuronal labeling was unrelated
      to the presence of signs of atrophy/degeneration. S-100beta expression was also
      unrelated to neuronal or glial apoptosis. S-100beta upregulation in ALS spinal
      cord suggests that the protein might be involved in cellular defense mechanisms
      against oxidative stress.

PMID- 10081919
TI  - Both protein kinase G dependent and independent mechanisms are involved in the
      modulation of glutamate release by nitric oxide in rat hippocampal nerve
      terminals.
AB  - We compared the effects of sodium nitroprusside (SNP), and of 8-bromo guanosine
      3',5'-cyclic monophosphate (8-BrcGMP), on the 4-aminopyridine (4-AP)-evoked Ca2+
      dependent release of glutamate from hippocampal nerve terminals and further
      investigated the role of protein kinase G (PKG) in this mechanism. SNP and 8
      BrcGMP dose-dependently inhibited glutamate release, however SNP concentrations
      ([SNP]) > 500 microM abolished the 4-AP evoked release, whereas 8-BrcGMP
      maximally inhibited the release by about 30%. The inhibition of glutamate release
      at low concentrations of SNP (< or = 5 microM) was of about 20%, and was reversed
      by Rp-8(4-chlorophenylthio)guanosine-3',5'-cyclic-monophosphorotioate )
      (RpCPTcGMP, 50 nM), but the inhibition at higher concentrations (5 < SNP < or =
      50 microM) was insensitive to the PKG inhibitor, but sensitive to [1 H
      (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one] (ODQ), which partially prevented the
      inhibition. [SNP] > 50 microM strongly inhibited glutamate release, and this was
      not reversed by either inhibitor. Furthermore, [SNP] < or = 50 microM enhanced
      cGMP formation, and the observed effects were not related to either decreased
      Ca2+ entry or ATP/ADP levels. Our results indicate that NO/PKG is the signaling
      pathway underlying the inhibition of glutamate release at low concentrations of
      NO, and imply that other NO-dependent, but PKG-independent, mechanisms are
      activated and have complementary roles at higher NO concentrations.

PMID- 10081920
TI  - Glutamate but not interleukin-6 influences the phosphorylation of tau in primary
      rat hippocampal neurons.
AB  - Alzheimer's disease (AD) is characterized by amyloid plaques, neuritic
      degenerations, disturbed glutamatergic neurotransmission and a peculiar
      inflammatory response. Diffuse plaques develop into neuritic plaques when
      neurites undergo degeneration in the plaque area. Hyperphosphorylation of tau
      proteins is a major step in neuritic pathology. Interleukin-6 (IL-6) has been
      found in diffuse and neuritic amyloid plaques in AD. Therefore the question
      arises whether IL-6 is involved in the transformation of diffuse into neuritic
      plaques by affecting tau phosphorylation. We investigated the influence of
      glutamate and IL-6 on tau phosphorylation in cultured primary rat hippocampal
      neurons. Glutamate but not IL-6 induced a dephosphorylation of tau. Furthermore
      IL-6 did not influence the glutamate-induced dephoshorylation of tau. We conclude
      that the role of IL-6 in AD is not related to the phosphorylation of tau.

PMID- 10081921
TI  - Effect of serum in medium on the expression of inducible nitric oxide synthase
      and superoxide dismutases in cultured C6 glioma cells.
AB  - It has been documented that C6 glioma cells can be changed into normal glial
      cells when they were cultured in serum free medium. In the present study, the
      expressions of inducible nitric oxide synthase (iNOS) and superoxide dismutase
      (SOD) were investigated. The mRNA level of iNOS was markedly increased by
      lipopolysaccharide (LPS) in cultured rat brain astrocytes (RBA-1) but not in C6
      glioma cells. However, increase of mRNA for iNOS by LPS can be obtained in C6
      glioma cells when they were cultured in serum free medium. The mRNA level of
      magnesium-SOD (Mn-SOD) was increased by LPS in both cells while the expression of
      constituted SOD (Cu,Zn-SOD) was not stimulated by LPS. Western blotting analysis
      indicating the amount of protein showed a similar change. After serum
      deprivation, the protein of iNOS or Mn-SOD was increased by LPS in C6 glioma
      cells in a way similar as that in RBA-1 cells. These results suggest that serum
      free conditioned C6 glioma cells were adapted to astroglial cell-like properties
      which may express more iNOS and Mn-SOD mRNA in the presence of LPS.

PMID- 10081922
TI  - Serotonin levels are abnormally elevated in the fetus of the monoamine oxidase-A
      deficient transgenic mouse.
AB  - Developmental changes in levels of serotonin, L-tryptophan and 5-hydroxyindol
      acetic acid (5-HIAA) were measured by high pressure liquid chromatography (HPLC)
      in the forebrain, brainstem and cervical cord of fetal, neonatal and adult mice
      from the wild strain C3H and the transgenic strain Tg8, created from the C3H line
      by the disruption of the gene encoding monoamine oxidase A. The results indicated
      that the absence of monoamine oxidase A activity in Tg8 mice results in
      abnormally high 5-hydroxytryptamine (5-HT) levels in all the central nervous
      structures and at all the studied developmental ages. Since serotonin levels were
      4-5 times larger in Tg8 than in C3H mice at gestational day 20, comparing the
      central network function at birth of C3H and Tg8 neonates should shed some light
      on the role of serotonin in prenatal network maturation.

PMID- 10081923
TI  - Chronic prenatal cocaine treatment down-regulates mu-opioid receptor mRNA
      expression in the brain of fetal Rhesus Macaque.
AB  - Ribonuclease protection assays (RPA) were performed to quantify mu-opioid
      receptor mRNA expression in specific brain regions of day 70 Rhesus Macaque
      fetuses that were exposed to cocaine (3 mg/kg) or saline from days 22-70 of
      gestation. The content of mu-receptor mRNA was high in the diencephalon and
      moderate in the mesencephalon. In contrast, mu-receptor mRNA was lightly
      expressed in areas such as the frontal cortex, striatum and the temporal lobe.
      The content of mu-opioid receptor mRNA was significantly higher in the
      diencephalon than in other brain regions (P < 0.001; n = 4). Cocaine exposure
      significantly decreased the expression of mu-receptor mRNA in the fetal
      diencephalon (P < 0.05; n = 4 in each group). Our data would indicate that
      prolonged gestational cocaine exposure causes mu-opioid receptor mRNA down
      regulation in specific brain regions of the fetus.

PMID- 10081924
TI  - Lanthanides stimulate [3H]tyramine binding in the rat striatum.
AB  - Low (up to 100 nM) and high (approximately 100 microM) concentrations of
      lanthanides and Ca2+-ions, respectively, stimulated [3H]tyramine binding ([3H]TY)
      to rat striatal membranes, a putative marker for the vesicular transporter of
      dopamine. On the other hand, lanthanides (approximately 100 microM) inhibited or
      stimulated TY binding in striatal and extrastriatal (cortex, cerebellum) tissues,
      respectively. The binding increases by lanthanum (La3+) appeared to depend on
      endogenous Ca2+, whereas, those induced in EDTA-pretreated membranes were Ca2+
      independent. The La3+-induced, apparent increase in the Bmax for [3H]TY binding
      seemed to reflect a retarded rate of dissociation of the ligand from its targets,
      rather than a larger availability of functionally-relevant, vesicular transport
      related TY sites. This indicates uncertain mechanisms of present La3+ effects.

PMID- 10081925
TI  - Deficits in phasic muscle force generation explain insufficient compensation for
      interaction torque in cerebellar patients.
AB  - A simple paradigm was used to investigate how patients with cerebellar lesions
      cope with the need to correct for joint interactions during a multi-joint
      movement. Normal subjects and patients with cerebellar degeneration performed
      fast unconstrained elbow flexions with the instruction to voluntarily fixate the
      shoulder joint. Angular kinematics and inverse dynamics analyses were performed.
      A susceptibility index quantified how strong-concomitant shoulder-motion depended
      on interactions from the elbow. Amplitudes of involuntary shoulder movements
      increased with elbow movement speed and were generally larger in patients.
      Susceptibility indices were smaller in patients, indicating a more variable
      compensatory response, however, increased with elbow movement speed. We conclude
      that patients were significantly less able to 'tune' their postural stabilizing
      response to match interaction torques. However, the velocity dependence of this
      effect points to a deficit in generating normal levels of phasic torque.

PMID- 10081926
TI  - Electroencephalographic cortical oscillations and saccadic eye movements in
      humans.
AB  - A model predicting different types of saccades has suggested that the presence of
      rhythmic brain activity determines whether a subject will produce regular or
      express saccades. We studied cortical oscillations preceding saccadic eye
      movements. Brain electrical activity was recorded in nine healthy adults
      continuously from 30 electrodes while subjects performed saccades. In a so-called
      gap condition multimodal latency distributions resulted. Express saccades were
      preceded by different oscillatory activity than regular saccades. This was a
      highly significant finding restricted to the alpha and beta bands of the EEG.
      Step-wise discriminant analysis showed that cortical oscillations measured from
      only few electrode sites allowed to predict reliably which type of saccade a
      subject will make. These findings support the notion that stimulus-induced
      oscillations of the human EEG may modulate thresholds for triggering saccades.

PMID- 10081927
TI  - Prolonged effects of 24-h total sleep deprivation on sleep and sleep EEG in the
      rat.
AB  - Long-term effects of 24-h sleep deprivation (SD) on sleep and sleep EEG were
      analyzed in male rats during 4 recovery days (Rec). An increase of total sleep
      time and non-rapid eye-movement (NREM) sleep was present during Rec 1-4, and of
      REM sleep in Rec 1 and in the dark periods of Rec 2 and 3. After the initial
      increase of slow-wave activity (SWA, mean EEG power density in the 0.75-4.0 Hz
      range) in NREM sleep, SWA declined below baseline until Rec 3. Sleep continuity
      was increased in Rec 1. The persistent effects of SD which are probably due to
      homeostatic and circadian facets of sleep regulation, must be taken into account
      in the design of SD studies.

PMID- 10081928
TI  - Synaptic facilitation in Helix neurons depends upon postsynaptic calcium and
      nitric oxide.
AB  - Intracellular tetanization of premotor interneurons for withdrawal in the snail.
      Helix lucorum produces long-term facilitation of synaptic inputs of these
      neurons. Using this model of plasticity we investigated the role of calcium in
      postsynaptic induction of synaptic facilitation. It was shown that, from the one
      hand, postsynaptic injection of calcium chelator EGTA completely abolishes
      potentiation and, from the other hand, injection of calcium chloride into the
      interneuron produces facilitation-like changes in the EPSP amplitude in this
      neuron. Therefore, not only necessity but also sufficiency of increasing of
      postsynaptic calcium for induction of synaptic potentiation was demonstrated. We
      also showed that inhibitor of nitric oxide synthase N-omega-nitro-L-arginine
      prevents development of postsynaptically induced facilitation what suggests that
      nitric oxide may participate in investigated synaptic facilitation as a
      retrograde messenger. These results support the idea that both invertebrates and
      vertebrates have common mechanisms underlying synaptic plasticity.

PMID- 10081929
TI  - Denervation does not affect the growth of rat vibrissae.
AB  - This study examines the hypothesis that neural factors influence the growth of
      rat vibrissae. We divided the vibrissae in rows alpha-delta, 1 and 2 and examined
      their regrowth during the first complete growth period in normal and nerve
      lesioned rats. The lesions used were denervation through neonatal capsaicin
      treatment, surgical sympathecomy in adult rats, neurectomy of the mandibular and
      buccal branches of the facial nerve in adult rats or division of the infraorbital
      nerve in adult rats. Normal vibrissae developed a length of 51.1 mm and a
      diameter of 178 microm (row alpha-delta), 44.1 mm and 181 microm (row 1) and 33.2
      mm and 165 microm (row 2). In all experimental groups the examined vibrissae
      developed a normal final length and proximal diameter. This indicates that local
      nerves do not influence vibrissal growth to any major extent.

PMID- 10081930
TI  - Serotonin-immunoreactive structures in the central nervous system of the garfish
      Lepisosteus productus (Semionotiformes, Osteichthyes).
AB  - Serotonin-immunoreactive (5HT-IR) neurons were investigated in the brain and
      rostral (cervical) spinal cord of the garfish, a non-teleost actinopterygian. The
      diencephalon contained a prominent 5HT-IR cell group consisting mainly of liquor
      contacting neurons in the hypothalamic periventricular wall. Their ependymofugal
      processes formed thick bundles or patches within the hypothalamus and then
      arborized profusely. Other groups of 5HT-IR cells were found in the dorsal
      thalamus and in the caudal cortex of the hypothalamic inferior lobe. In the
      caudal brainstem, 5HT-IR cells were predominant in the raphe region. The spinal
      5HT-IR cells were scattered rostrocaudally in the ventromedial zone. The
      structure corresponding to the submeningeal serotonergic system in the ventral
      spinal cord of the lamprey and stingray was demonstrated also in the garfish.

PMID- 10081931
TI  - Subcellular muscarinic enhancement of excitability and Ca2+-signals in CA1
      dendrites in rat hippocampal slice.
AB  - The cholinergic system is involved in Ca2+-dependent models of learning. To study
      subcellular modulation, we evoked 50-100 microm long dendritic Ca2+-responses by
      focal pressure application of glutamate. These Ca2+-responses were augmented by
      +70% by focally applied carbachol. This atropine-sensitive augmentation started
      within 1 s concurrent to an augmentation of the glutamate-evoked somatic
      depolarization and firing. Tetrodotoxin reduced the Ca2+-response to glutamate by
      60-80% while, after having restored the Ca2+-signal by increasing the application
      of glutamate, its muscarinic augmentation was reduced from +73 to +30%. Lithium
      (2 mM, >2 h) slowed and reduced augmentation of Ca2+-signals and blocked
      augmentation of the glutamate-evoked depolarization and firing, but not
      suppression of the slow after-hyperpolarization following repetitive discharge.
      Thus, several mechanisms contribute to muscarinic augmentation of Ca2+-signals.

PMID- 10081932
TI  - L-type calcium channels but not N-methyl-D-aspartate receptor channels mediate
      rhythmic activity induced by cholinergic agonist in motoneurons from turtle
      spinal cord slices.
AB  - Rhythmic activity induced by different combinations of N-methyl-D-aspartate
      (NMDA), serotonin (5-HT), muscarine and D-tubocurarine was monitored
      intracellularly in lumbar motoneurons in a slice preparation from adult turtles.
      Low concentration of NMDA (7.5-15 microM) combined with 5-HT (10-80 microM)
      induced rhythmic motoneuron discharge which was underlied by intrinsic voltage
      oscillations resistant to tetrodotoxin. This oscillatory activity was abolished
      by 2-amino-5-phosphonopentanoic acid (AP5), a competitive blocker of NMDA
      receptors and by nifedipine a selective blocker of L-type calcium channels. In
      contrast, rhythmicity induced by the cholinergic agents muscarine and d
      tubocurarine was abolished by nifedipine but not by AP5 nor by high [Mg2+]o.
      These results show that different receptor agonists induce intrinsic oscillations
      in mature motoneurons by independent routes. Each oscillatory mechanism depends
      on L-type calcium channels but only NMDA/5-HT-induced oscillations depend on
      voltage-sensitive NMDA-activated ionophores.

PMID- 10081933
TI  - Electrophysiological transcortical diaschisis after middle cerebral artery
      occlusion (MCAO) in rats.
AB  - Remote changes in brain function following stroke are called diaschisis. These
      remote effects may contribute to the neurological deficit following brain
      infarction; in addition they may lead to post-stroke epilepsy and affect
      functional recovery. In the present study we addressed the question of whether an
      increase in excitability can be observed contralateral to middle cerebral artery
      (MCA) infarction. Permanent occlusion of the middle cerebral artery (MCAO) was
      induced experimentally in rats with an intraluminal silicon-coated filament.
      Seven days later, brain excitability was tested with extracellulare recording
      techniques in neocortical coronal brain slices using a paired-pulse stimulus
      protocol. In rats with MCAO, excitability was increased in the neocortex
      contralateral to the infarction compared with the control group. These
      alterations extended through wide parts of the contralateral neocortex. The study
      demonstrates that MCAO causes transcallosal electrophysiological diaschisis.
      Together with results obtained previously with photothrombotic cortical lesions,
      it can be concluded that these remote effects are not due to characteristics of
      the individual lesion model, but are common consequences of brain lesions.

PMID- 10081934
TI  - A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist
      oppose each others effects in a genetic rat epilepsy model.
AB  - The WAG/RIJ rats exhibit spontaneously occurring spike-wave discharges (SWD)
      accompanied by behavioural phenomena, with characteristics similar to the human
      absence type epilepsy. To study the mechanisms involved in this type of
      epileptiform activity we investigated the effects of the serotonin-1A (5-HT1A)
      receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the N
      methyl-D-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H
      dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801). Intracerebroventricular
      (i.c.v.) injection of 8-OH-DPAT caused marked, dose dependent increase, MK-801 a
      decrease in the cumulative duration and number of spike-wave discharges.
      Pretreatment with MK-801 (10 microg/rat i.c.v.) abolished the increase caused by
      8-OH-DPAT (20 microg/rat i.c.v.), but the decrease in SWD to MK-801 was
      counterbalanced by 8-OH-DPAT. These data provide evidence for an interaction of
      glutamatergic and serotonergic mechanisms in the triggering and maintenance of
      epileptic activity in this genetic model of absence epilepsy.

PMID- 10081935
TI  - GABA may function tonically via GABA(A) receptors to inhibit hypotension and
      bradycardia by L-DOPA microinjected into depressor sites of the nucleus tractus
      solitarii in anesthetized rats.
AB  - We have proposed that DOPA is a transmitter of the primary baroreceptor afferents
      terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative
      inhibitory neuromodulator for baroreflex inputs in the NTS. GABA may inhibit
      DOPAergic transmission. Drugs were microinjected into depressor sites of the NTS
      in anesthetized rats. DOPA (10-60 ng) elicited dose-dependent depressor
      responses. GABA (3-300 ng) elicited dose-dependent pressor responses. Nipecotic
      acid (100 ng) elicited pressor responses. Bicuculline (10 ng) elicited depressor
      responses. Responses to DOPA (30 ng) were inhibited by pretreatment with GABA and
      nipecotic acid, but potentiated by bicuculline, when vascular responses to
      pretreated drugs returned to basal levels. DOPA ME, a competitive DOPA
      antagonist, did not displace specific [3H]GABA binding. Prior DOPA ME (1 microg)
      inhibited by one-half pressor responses to 300 ng GABA. GABA seems to inhibit
      tonically via GABA(A) receptors depressor responses to DOPA and to elicit pressor
      responses partially by inhibition of tonic function of endogenous DOPA to
      activate depressor sites in the NTS. These findings further support the above
      proposal.

PMID- 10081936
TI  - Do beta-amyloid (Abeta) deposits in patients with Alzheimer's disease and Down's
      syndrome grow according to the log-normal model?
AB  - The size frequency distributions of diffuse, primitive and classic beta-amyloid
      (Abeta) deposits were studied in single sections of cortical tissue from patients
      with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those
      predicted by the log-normal model. In a sample of brain regions, these size
      distributions were compared with those obtained by serial reconstruction through
      the tissue and the data used to adjust the size distributions obtained in single
      sections. The adjusted size distributions of the diffuse, primitive and classic
      deposits deviated significantly from a log-normal model in AD and DS, the
      greatest deviations from the model being observed in AD. More Abeta deposits were
      observed close to the mean and fewer in the larger size classes than predicted by
      the model. Hence, the growth of Abeta deposits in AD and DS does not strictly
      follow the log-normal model, deposits growing to within a more restricted size
      range than predicted. However, Abeta deposits grow to a larger size in DS
      compared with AD which may reflect differences in the mechanism of Abeta
      formation.

PMID- 10081937
TI  - Molecular cloning of the cone-rod homeobox gene (Crx) from the rat and its
      temporal expression pattern in the retina under a daily light-dark cycle.
AB  - The primary structure of the cone-rod homeobox protein (CRX), a member of the OTX
      like homeobox protein family, in the rat was deduced from the cDNA nucleotide
      sequence. The deduced protein consisted of 299 amino acid residues with motifs
      conserved in mammalian CRXs, and was 98% identical to mouse CRX. Northern blot
      analysis showed that Crx mRNA levels in the rat retina were constant under a
      daily light-dark cycle. These findings suggest that the expression mechanism of
      rat Crx in the retina was different from that in the pineal, where Crx mRNA
      exhibits a daily expression rhythm.

PMID- 10081938
TI  - Morphological characterization of relationship between gap junctions and
      gonadotropin releasing hormone nerve terminals in the rat median eminence.
AB  - The present study aimed to reveal possible morphological relationships between
      gonadotropin-releasing hormone (GnRH) nerve terminals and gap junctions in the
      median eminence. Coronal brain sections from castrated male rats were dual
      immunostained with GnRH and either connexin 26, 32, or 43, and examined by
      confocal laser microscopy. Connexin 43-immunoreactive puncta were distributed
      between GnRH-immunoreactive fibers, and some of them were colocalized with GnRH
      immunoreactivities. Dual immunostaining with connexin 43 and glial fibrillary
      acidic protein revealed that most of the puncta were located in astrocytes. At
      the immunoelectron microscopic level, connexin 43-immunoreactivities were mainly
      located on the plasma membranes of glial-like processes. Few connexin 26- or
      connexin 32-immunoreactivities were found in the median eminence. The present
      results indicate the possibility that gap junctions play a role in the GnRH
      release at the median eminence.

PMID- 10081939
TI  - Analyses of taste nerve responses with special reference to possible receptor
      mechanisms of umami taste in the rat.
AB  - Umami substances such as monopotassium L-glutamate (MPG) and 5'-inosine
      monophosphate (IMP) elicit a unique taste called 'umami' in humans. To elucidate
      the umami receptor mechanism in rats, we examined taste responses of the chorda
      tympani nerve by using three ionotropic glutamate receptor agonists, NMDA, KA and
      AMPA, a mGluR4 agonist, L-AP4, and a specific mGluR4 antagonist, MAP4, and an
      anti-sweet peptide, gurmarin. When IMP was added, synergistic responses were
      shown only for MPG and L-AP4, but not for NMDA, KA and AMPA. MAP4 enhanced the
      responses to MPG and L-AP4. Gurmarin suppressed the synergistic responses to
      mixtures of MPG and IMP or L-AP4 and IMP. These results suggest that glutamate
      and L-AP4 bind both the sweet-responsive macromolecule and mGluR4, but the
      synergism occurs only on the macromolecule.

PMID- 10081940
TI  - Presence of glutamate receptor subtypes on barosensitive neurons in the nucleus
      tractus solitarius of the dog.
AB  - Afferent baroreceptor information is transmitted to the nucleus tractus
      solitarius (NTS) in the dorsal medulla where glutamate is thought to be the
      primary neurotransmitter. However, the subtypes of glutamate receptors involved
      in the baroreflex remain to be established. The present study compared the
      distribution of immunohistochemically labeled ionotropic receptor subtypes to the
      distribution of physiologically stimulated barosensitive neurons in the NTS of
      the dog and also identified ionotropic receptor subtypes located on barosensitive
      neurons. Both NMDA and non-NMDA receptors were located in barosensitive areas and
      on barosensitive neurons, suggesting that both may be involved in the baroreflex.

PMID- 10081941
TI  - The effect of streptozotocin-diabetes on beta-endorphin level and
      proopiomelanocortin gene expression in the rat pituitary.
AB  - Streptozotocin-induced diabetes for 4 weeks resulted in a decrease in
      proopiomelanocortin (POMC) mRNA in both the anterior lobe (AL) and the neuro
      intermediate lobe (NIL) of the rat pituitary. The beta-endorphin levels decreased
      in the NIL but not in the AL. It is concluded that the synthesis of POMC in the
      pituitary is inhibited in diabetic rats and that there is a decrease in beta
      endorphin release from the anterior pituitary.

PMID- 10081942
TI  - Kynurenic acid inhibits circulatory responses to intracisternally injected L
      proline in conscious rats.
AB  - To investigate the modes of action of potential neurotransmitters for
      cardiovascular control, amino acids and an antagonist were injected
      intracisternally into conscious rats. Blood pressure and superior mesenteric flow
      were measured with cannulae and electromagnetic flow probes that had been
      implanted in a previous operation under pentobarbitone anaesthesia. L-Proline, L
      glutamate and L-arginine (10, 2 and 10 micromol, respectively) caused similar
      increases in blood pressure and mesenteric vascular resistance. Prior injection
      of kynurenic acid (0.1 micromol), a broad spectrum antagonist of ionotropic
      excitatory amino acid receptors, completely blocked the circulatory effects of L
      proline, significantly reduced those of L-glutamate but had little effect on
      responses to L-arginine. These results suggest that the central pressor pathways
      activated by L-proline, a potential endogenous neurotransmitter, are mediated by
      ionotropic excitatory amino acid receptors.

PMID- 10081943
TI  - Increase of neuron-specific enolase in patients with Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative human disorder with
      an incidence of one case per 1000000 per year. Recently new diagnostic tests such
      as neuron-specific enolase (NSE), S-100, tau-protein and protein 14-3-3 have been
      established as markers in prion diseases. NSE is elevated in case of rapid nerve
      cell loss so quantitative measurement of NSE in cerebrospinal fluid (CSF) might
      correlate with the disease progression. To further evaluate this hypothesis we
      analysed longitudinal CSF samples from 16 CJD patients. The first spinal tap was
      taken two weeks after the first clinical signs of a neurodegenerative disorder.
      This showed an elevation of NSE which continued during the course of the disease.
      Longitudinal examination of neuron-specific enolase in cerebrospinal fluid
      therefore may be useful for differentiation between CJD and other dementias.

PMID- 10081945
TI  - Classifying stress urinary incontinence.

PMID- 10081944
TI  - Expression of mouse semaphorin H mRNA in the inner ear of mouse fetuses.
AB  - Semaphorins constitute a large family of secreted and cell-surfaced proteins that
      appear to function as chemorepellents to guide axons. We examined the expression
      pattern of M-semaH mRNA in the inner ear of mouse fetuses by in situ
      hybridization histochemistry. M-semaH mRNA expression was high in the
      endolymphatic sac involved in endolymph homeostasis. It was also high in the
      semicircular ducts except for the crista ampullaris, whereas no expression was
      detected in the epithelium of cochlear ducts.

PMID- 10081946
TI  - Sequential changes in voiding dynamics related to the development of detrusor
      instability in women with stress urinary incontinence.
AB  - We evaluated 31 women who had undergone a conservative treatment regimen for
      stress urinary incontinence and who, during the treatment period, were assessed
      twice urodynamically (by cystometry and pressure/flow study) at an interval of
      months between the two examinations. Seventeen (Group 1) had stable bladders at
      time 1 and detrusor instability (DI) after a mean of 12 months (time 2). Fourteen
      (Group 2) had stable bladders both at time 1 and after a mean of 15 months. Of
      the urodynamic parameters evaluated, the opening detrusor pressure (pdet.op)
      reflected the height of the bladder neck pressure rise that normally occurs
      during the opening phase of micturition and that is overcome by the detrusor
      contraction pressure at the onset of flow. At the second testing, Group 1
      patients showed greater detrusor strength. They also showed a more elevated
      pdet.op (= a more elevated bladder neck pressure rise during the onset of voiding
      detrusor contraction), which may have been necessary to ensure an enhanced
      bladder contractility level. Indeed, a higher rise in pressure, hence in muscular
      tension, at the bladder neck region should obviously lead to increased afferent
      signals from tension receptors, and positive feedback to the detrusor of such
      increased signals may yield more intense neural stimulation. This would amplify
      the facilitating effect on bladder contractility of a possible DI-related
      decrease in electrical resistance between the detrusor smooth muscle cells.

PMID- 10081947
TI  - Detrusor instability and low compliance may represent different levels of
      disturbance in peripheral feedback control of the micturition reflex.
AB  - BACKGROUND: Detrusor instability is a major cause of urinary incontinence in
      females. Its cause is unknown. Diagnosis is made with cystometry. A phasic
      pressure rise during cystometry diagnoses the unstable detrusor, and a non-phasic
      pressure rise the stable "low-compliance" detrusor. The aim was to test the
      hypothesis that such cystometric findings may represent different levels of
      disturbance in peripheral feedback control of a prematurely activated, but
      otherwise normal micturition reflex. Of 169 neurologically normal female
      incontinent patients (mean age, 50; mean parity, 3) urodynamically tested, 40 had
      detrusor instability and 16 had low compliance. Digital support of bladder base
      tested the peripheral control mechanism, and hand-washing the central control
      mechanism. The data were applied to a non-linear feedback equation with one
      variable, X(NEXT) = cX(1 - X), where c = central inhibition and X = fraction of
      possible nerve impulses in the micturition circuit. RESULTS: During filling, all
      16 low-compliance patients had a bladder in the activated but stable closed
      state. Fourteen of the detrusor instability group could not suppress the
      micturition reflex and lost urine. During hand-washing, unexpectedly greater
      urine loss was noted in the low-compliance group (13 of 16) than in the detrusor
      instability group (24 of 40), chi2 (P < 0.005). With digital stretching, urge
      symptoms disappeared within a few seconds in 18/20 patients, and detrusor
      instability was suppressed in six patients. INTERPRETATION: The bladder has two
      stable states: open and closed. Closure is regulated by central and peripheral
      components. In the female, the peripheral component is controlled by the pelvic
      floor stretching the vagina to support the urine column. This prevents
      inappropriate activation of the micturition stretch receptors. In patients with
      low compliance, this peripheral control mechanism was sufficient to maintain the
      micturition reflex in an activated but stable closed state. In patients with
      detrusor instability, the micturition reflex could not be suppressed, swinging
      between the open and closed states. CONCLUSIONS: Demonstration of a peripheral
      musculoelastic control mechanism unlocks a new direction for management of female
      patients with non-neurological bladder instability. It is possible, using simple
      clinical methods based on digital vaginal stretching, to predict cure of
      instability by surgical tightening of the vagina and its supporting ligaments.

PMID- 10081948
TI  - Neurophysiological study of primary nocturnal enuresis.
AB  - The purpose of this study was to investigate nervous system involvement in
      primary nocturnal enuresis by using electrophysiological techniques. Nineteen
      boys with primary nocturnal enuresis and 25 boys without uroneurological
      abnormalities were included. Data about their psychomotor development,
      micturition, and defecation were obtained by interviewing the boys and their
      parents. The penile sensory threshold for electrical stimuli was determined.
      Single and averaged bulbocavernosus reflex (BCR), and averaged pudendal
      somatosensory evoked potentials (PSEP) to electrical stimulation, were recorded.
      The only statistically significant difference found in enuretic children was
      longer latencies of averaged BCR to single electrical stimulation (P = 0.03). No
      significant BCR latency differences to stimulation with double electrical pulses
      and no PSEP latency differences were found. By using electrophysiological
      techniques, differences between the enuretic and control group of boys were
      demonstrated. Our results can be interpreted as indicating hypoexcitability of
      sphincter nuclei. Along with the reported hyperexcitability of bladder motor
      nuclei, a minor dysfunction in the neurocontrol of the lower urinary tract, in at
      least a subgroup of enuretic children, can be postulated.

PMID- 10081949
TI  - Urethral pressure response to cough and voluntary perineal contraction in men
      without previous pelvic surgery.
AB  - The aim of this study was to analyze the urethral pressure responses to cough in
      men to better characterize the neurogenic mechanisms of male urethral function. A
      prospective study was carried out on 41 men referred for urodynamic assessment.
      Urethral pressure profiles at rest and during coughing, and urethral pressure
      response to voluntary perineal contraction were recorded and analyzed in relation
      to the neurological status of the patients. Voluntary perineal contraction
      resulted in a urethral pressure increase (delta pU) of approximately 150 cm H2O
      in neurologically normal patients. Delta pU could be reduced to any degree in
      patients with either central or peripheral neurological lesions. Urethral
      pressure response to cough could be easily classified into two main patterns.
      Pattern I was characterized by a marked increase in urethral closure pressure
      during the cough (ratio of urethral to rectal pressure increase: 248 +/- 106%),
      occurring at the distal part of the posterior urethra. All the neurologically
      normal patients and the majority of those with upper motoneuron lesions had a
      pattern I response. Pattern II was defined by the absence of any significant
      increase in urethral closure pressure at any site of the posterior urethra and
      was observed in 80% of the patients with signs of lower motoneuron lesions. The
      pattern of the response to cough was significantly related to the neurological
      status of the patients (P < 0.001). It was dissociated from the response to
      voluntary contraction, as would be expected for a reflex versus a voluntary
      response in neurological patients.

PMID- 10081950
TI  - Case report: acute urinary retention secondary to Isaacs' syndrome.
AB  - We report an unusual case of acute urinary retention secondary to Isaacs'
      syndrome due to external urethral sphincter spasm. The patient was able to resume
      spontaneous voiding after the treatment of the underlying disease. At 6-month
      follow-up, there were no voiding complaints.

PMID- 10081951
TI  - Urodynamics in acetone-induced cystitis of anesthetized rats.
AB  - We examined the bladder function of cystitis models induced by intravesical
      acetone instillation in urethane-anesthetized rats. Acetone (0.35 ml) at 10, 30,
      or 50% concentration or deionized water (sham-treatment) was instilled into the
      bladder via the cannula which was inserted into the lumen. Acetone was withdrawn
      90 sec after instillation and the bladder lumen was washed with saline after 15
      min. One hour later, the cystometrogram induced by transvesical infusion of
      saline (3.3 ml/hr) was measured. During cystometrography of normal (non-treated)
      or sham-treated group, the time required to cause micturition, reflecting bladder
      capacity, was 9.6 +/- 0.9 (n = 7) or 10.0 +/- 0.8 min (n = 6), respectively. In
      the 10% acetone-treated group, the bladder capacity was similar to that in the
      normal or sham group. In the 30% acetone group, the time to micturition was 4.4
      +/- 0.4 min (n = 7), indicating decreased bladder capacity, although the
      micturition pressure and the threshold pressure were not significantly different
      from those in the normal or sham group. However, in the 50% acetone group, the
      micturition reflex disappeared. In isolated rat bladder strips, contractile
      responses to carbachol or electrical field stimulation in the sham and 30%
      acetone group were similar. While, both responses in isolated strips from the 50%
      acetone group were reduced. The degree of damage from degeneration and
      desquamation of epithelium and hemorrhage in the bladder tissue from the 30%
      acetone group was less prominent than in the 50% acetone group. Additionally,
      some tissue from the 50% acetone group showed degeneration of muscle layer. The
      effects of three drugs were investigated in the 30% acetone group which showed
      increased urinary frequency. Baclofen (100 microg/kg, i.v.) and morphine (100
      microg/kg, i.v.) increased significantly the bladder capacity and the threshold
      pressure. Atropine (10 microg/kg, i.v.) decreased the micturition pressure. These
      results suggest that cystitis models induced by intravesical instillation of 30%
      acetone may be valuable for evaluating drugs for the treatment of urinary
      frequency.

PMID- 10081952
TI  - Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder
      to repetitive stimulation and in vitro ischemia.
AB  - The effect of repetitive stimulation, in the presence and absence of diltiazem or
      pinacidil, on the contractile responses of isolated strips of rabbit bladder
      detrusor to field stimulation and carbachol, after 2 hr of incubation in a medium
      that serves as an in vitro model of ischemia (oxygen and substrate depleted
      Tyrode's solution), was determined. Our results are summarized as follows: a) The
      magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by
      repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with
      diltiazem (50 microM) inhibited the contractile responses to field stimulation
      (FS) and carbachol by 43 and 50%, respectively. Pinacidil (100 microM) inhibited
      the contractile responses to FS and carbachol by 37 and 32%, respectively. c)
      Neither diltiazem nor pinacidil protected the bladder strips against the effects
      of 2 hr of incubation in in vitro ischemia medium. However, d) both pinacidil and
      diltiazem reduced the level of contractile dysfunctions induced by repetitive
      stimulation. In conclusion, the contractile response to FS was significantly more
      sensitive to in vitro ischemia and repetitive stimulation than was the
      contractile response to carbachol. Both diltiazem and pinacidil protected the
      contractile responses to FS and carbachol from the degenerative effects of
      repetitive stimulation, but not from the effects of in vitro ischemia.

PMID- 10081953
TI  - The standardization of terminology in neurogenic lower urinary tract dysfunction:
      with suggestions for diagnostic procedures. International Continence Society
      Standardization Committee.

PMID- 10081954
TI  - Solution structure of potassium channel-inhibiting scorpion toxin Lq2.
AB  - Lq2 is a unique scorpion toxin. Acting from the extracellular side, Lq2 blocks
      the ion conduction pore in not only the voltage- and Ca2+ -activated channels,
      but also the inward-rectifier K+ channels. This finding argues that the three
      dimensional structures of the pores in these K+ channels are similar. However,
      the amino acid sequences that form the external part of the pore are minimally
      conserved among the various classes of K+ channels. Because Lq2 can bind to all
      the three classes of K+ channels, we can use Lq2 as a structural probe to examine
      how the non-conserved pore-forming sequences are arranged in space to form
      similar pore structures. In the present study, we determined the three
      dimensional structure of Lq2 using nuclear magnetic resonance (NMR) techniques.
      Lq2 consists of an alpha-helix (residues S10 to L20) and a beta-sheet, connected
      by an alphabeta3 loop (residues N22 to N24). The beta-sheet has two well-defined
      anti-parallel strands (residues G26 to M29 and residues K32 to C35), which are
      connected by a type I' beta-turn centered between residues N30 and K31. The N
      terminal segment (residues Z1 to T8) appears to form a quasi-third strand of the
      beta-sheet.

PMID- 10081955
TI  - Hemoglobins from deep-sea hydrothermal vent scaleworms of the genus
      Branchipolynoe: a new type of quaternary structure.
AB  - Branchipolynoe symmytilida and B. seepensis are two scaleworms (Polychaeta;
      Polynoidae) living commensally in the mantle cavity of deep-sea hydrothermal vent
      and cold-seep mussels. In contrast with littoral members of this family, the two
      species exhibit a large amount of extracellular hemoglobin (Hb) in their coelomic
      fluid. Gel filtration revealed the existence of four different Hbs: one minor,
      high molecular mass (3x10(6) Da) Hb, V1-Hb, reminiscent of a vascular hexagonal
      bilayer annelid Hb; two major coelomic Hbs, C1-Hb, and C2-Hb, with unusual masses
      for extracellular annelid Hbs of 153 and 124 kDa respectively; and a minor
      probably coelomic Hb of 23 kDa (C3-Hb). Using electrospray ionization mass
      spectrometry, SDS-PAGE after subtilisin treatment, and tandem mass spectrometry,
      we showed that C1-Hb is a trimer of a 57,996 Da chain and C2-Hb is a dimer of a
      57,648 Da chain, each chain being a four-domain/four-heme polypeptide. This
      multimeric, multidomain arrangement is unique among annelid Hbs and appears
      different from that of other known multidomain Hbs.

PMID- 10081956
TI  - Characterization and functional properties of the extracellular coelomic
      hemoglobins from the deep-sea, hydrothermal vent scaleworm Branchipolynoe
      symmytilida.
AB  - Polychaete species belonging to the genus Branchipolynoe are commensal with
      mussels from deep-sea hydrothermal vents and cold-seeps. Possessing hemoglobins
      (Hbs), the species B. symmytilida, which is found in the mussel Bathymodiolus
      thermophilus on the East Pacific Rise, is exceptional in a family normally devoid
      of respiratory pigments. In a previous paper we described two major coelomic
      extracellular hemoglobins with unique quaternary structures. Aiming to discern
      respiratory adaptations to the highly variable hydrothermal environment, this
      paper characterizes the functional properties of these Hbs and the coelomic
      fluid. The two major hemoglobins (C1 and C2) exhibit spectrophotometric
      characteristics of both intra- and extracellular hemoglobins. However, their
      amino acid content is very different from other known hemoglobins and is
      characterized by a high proportion of alanine and glycine (up to 40% cumulated in
      C1). C1 and C2 differ markedly by their cysteine content (0.8% and 13%
      respectively). The coelomic fluid exhibits a strong buffer capacity due to the
      high hemoglobin content (3 mM heme). In vitro, CO2 accumulation (up to 10-12 mM
      CO2 for PCO2 = 7.5 Torr) occurs with limited pH changes and is only partly
      accounted for by carbamino-Hb formation. The two hemoglobins exhibit high oxygen
      affinities (P50 0.4 Torr for C1 and 0.9 Torr for C2, at 10 degrees C, pH 8) and a
      normal Bohr effect (phi values ranging from -0.54 and -0.37 at 10 degrees C, to 
      0.24 and -0.28 at 30 degrees C, for C1 and C2, respectively). Cooperativity
      values range from 0.8 to 1.9 for C1 and from 0.8 to 1.7 for C2. The temperature
      sensitivity of O2 affinity reflect deltaH values that decrease from -30 to -60 kJ
      x mol(-1) with increasing pH. C2 exhibits a slight specific effect of CO2 on
      oxygenation properties.

PMID- 10081957
TI  - Steady-state fluorescence and circular dichroism of trout hemoglobins I and IV
      interacting with tributyltin.
AB  - The effect of tributyltin chloride (TBTC) on rainbow trout (Salmo irideus)
      hemoglobin I (HbI) and hemoglobin IV (HbIV) was characterized by the steady-state
      fluorescence of intrinsic and extrinsic fluorescent probes. The fluorescence
      emission spectrum (lambdaex 280 nm) is greatly increased in intensity by the
      presence of the organotin in both proteins. Circular dichroism spectra in the
      same samples show a small decrease in theta222, a measure correlated with the
      percentage of the alpha-helical content. Morever, important changes in near-UV,
      Soret, and visible regions of CD were induced by TBTC. The correlation of data
      obtained with trout hemoglobins (HbI and HbIV) with similar measurements on
      globins suggests that the presence of heme is necessary for the interaction of
      the organotin compound with the proteins.

PMID- 10081958
TI  - Molecular dynamics and accuracy of NMR structures: effects of error bounds and
      data removal.
AB  - The effect of internal dynamics on the accuracy of nuclear magnetic resonance
      (NMR) structures was studied in detail using model distance restraint sets (DRS)
      generated from a 6.6 nanosecond molecular dynamics trajectory of bovine
      pancreatic trypsin inhibitor. The model data included the effects of internal
      dynamics in a very realistic way. Structure calculations using different error
      estimates were performed with iterative removal of systematically violated
      restraints. The accuracy of each calculated structure was measured as the atomic
      root mean square (RMS) difference to the optimized average structure derived from
      the trajectory by structure factors refinement. Many of the distance restraints
      were derived from NOEs that were significantly affected by internal dynamics.
      Depending on the error bounds used, these distance restraints seriously distorted
      the structure, leading to deviations from the coordinate average of the dynamics
      trajectory even in rigid regions. Increasing error bounds uniformly for all
      distance restraints relieved the strain on the structures. However, the accuracy
      did not improve. Significant improvement of accuracy was obtained by identifying
      inconsistent restraints with violation analysis, and excluding them from the
      calculation. The highest accuracy was obtained by setting bounds rather tightly,
      and removing about a third of the restraints. The limiting accuracy for all
      backbone atoms was between 0.6 and 0.7 A. Also, the precision of the structures
      increased with removal of inconsistent restraints, indicating that a high
      precision is not simply the consequence of tight error bounds but of the
      consistency of the DRS. The precision consistently overestimated the accuracy.

PMID- 10081959
TI  - A new Hybrid Monte Carlo algorithm for protein potential function test and
      structure refinement.
AB  - A new Hybrid Monte Carlo (HMC) algorithm has been developed to test protein
      potential functions and, ultimately, refine protein structures. The main
      principle of this algorithm is, in each cycle, a new trial conformation is
      generated by carrying out a short period of molecular dynamics (MD) iterations
      with a set of random parameters (including the MD time step, the number of MD
      steps, the MD temperature, and the seed for initial MD velocity assignment); then
      to accept or reject the new conformation on the basis of the Metropolis
      criterion. The novelty in this paper is that the potential in MD iterations is
      different from that in the MC step. In the former, it is a molecular mechanics
      potential, in the latter it is a knowledge-based potential (KBP). Directed by the
      KBP, the MD iteration is used to search conformational space for realistic
      conformations with low KBP energy. It circumvents the difficulty in using KBP
      functions directly in MD simulation, as KBP functions are typically incomplete,
      and do not always have continuous derivatives required for the calculation of the
      forces. The new algorithm has been tested in explorations of conformational
      space. In these test calculations the KBP energy was found to drop below the
      value for the native conformation, and the correlation between the root mean
      square deviation (RMSD) and the KBP energy was shown to be different from the
      test results in other references. At the present time, the algorithm is useful
      for testing new KBP functions. Furthermore, if a KBP function can be found for
      which the native conformation has the lowest energy and the energy/RMSD
      correlation is good, then this new algorithm also will be a tool for refinement
      of the theory-based structural models.

PMID- 10081960
TI  - The folding funnel landscape for the peptide Met-enkephalin.
AB  - We study the free energy landscape of the small peptide Met-enkephalin. Our data
      were obtained from a generalized-ensemble Monte Carlo simulation taking the
      interactions among all atoms into account. We show that the free energy landscape
      resembles that of a funnel, indicating that this peptide is a good folder. Our
      work demonstrates that the energy landscape picture and folding concept,
      developed in the context of simplified protein models, can also be used to
      describe the folding in more realistic models.

PMID- 10081961
TI  - Exploring protein interiors: the role of a buried histidine in the KH module
      fold.
AB  - The K-homology (KH) module is a novel RNA-binding motif. The structures of a
      representative KH motif from vigilin (vig-KH6) and of the first KH domain of fmr1
      have been recently solved by nuclear magnetic resonance (NMR) and automated
      assignment-refinement techniques (ARIA). While a hydrophobic residue is found at
      position 21 in most of the KH modules, a buried His is conserved in all the 15 KH
      repeats of vigilin. This position must therefore have a key structural role in
      stabilizing the hydrophobic core. In the present work, we have addressed the
      following questions in order to obtain a detailed description of the role of His
      21: i) what is the exact role of the histidine in the hydrophobic core of vig
      KH6? ii) can we define the interactions that allow a conserved buried position to
      be occupied by a histidine both in vig-KH6 and in the whole vigilin KH sub
      family? iii) how is the structure and stability of vig-KH6 influenced by the
      state of protonation of this histidine? To answer these questions, we have
      carried out an extensive refinement of the vig-KH6 structure using both an
      improved ARIA protocol starting from different initial structures and
      successively running restrained and unrestrained trajectories in water. An
      analysis of the stability of secondary structural elements, solvent
      accessibility, and hydrogen bonding patterns allows hypothesis on the structural
      role of residue His 21 and on the interactions that this residue forms with the
      environment. The importance of the protonation state of His 21 on the stability
      of the KH fold was addressed and validated by experimental results.

PMID- 10081962
TI  - Hydrogen bonds between short polar side chains and peptide backbone: prevalence
      in proteins and effects on helix-forming propensities.
AB  - A survey of 322 proteins showed that the short polar (SP) side chains of four
      residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen
      bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26%
      of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the
      N terminal of a helix, the contribution to helix stability by a hydrogen bond
      with the amide of the N3 or N2 residue is well established. When an SP residue is
      in the middle of a helix, the side chain is unlikely to form hydrogen bonds with
      neighboring backbone amides for steric and geometric reasons. In essence the SP
      side chain competes with the backbone carbonyl for the same hydrogen-bonding
      partner (i.e., the backbone amide) and thus SP residues tend to break backbone
      carbonyl-amide hydrogen bonds. The proposition that this is the origin for the
      low propensities of SP residues in the middle of alpha helices (relative to those
      of nonpolar residues) was tested. The combined effects of restricting side-chain
      rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA,
      1992;89:5937-5941; Proteins, 1994;19:85-97) and excluding side- chain to backbone
      hydrogen bonds by the helix were quantitatively analyzed. These were found to
      correlate strongly with four experimentally determined scales of helix-forming
      propensities. The correlation coefficients ranged from 0.72 to 0.87, which are
      comparable to those found for nonpolar residues (for which only the loss of side
      chain conformational entropy needs to be considered).

PMID- 10081963
TI  - Evaluation and improvement of multiple sequence methods for protein secondary
      structure prediction.
AB  - A new dataset of 396 protein domains is developed and used to evaluate the
      performance of the protein secondary structure prediction algorithms DSC, PHD,
      NNSSP, and PREDATOR. The maximum theoretical Q3 accuracy for combination of these
      methods is shown to be 78%. A simple consensus prediction on the 396 domains,
      with automatically generated multiple sequence alignments gives an average Q3
      prediction accuracy of 72.9%. This is a 1% improvement over PHD, which was the
      best single method evaluated. Segment Overlap Accuracy (SOV) is 75.4% for the
      consensus method on the 396-protein set. The secondary structure definition
      method DSSP defines 8 states, but these are reduced by most authors to 3 for
      prediction. Application of the different published 8- to 3-state reduction
      methods shows variation of over 3% on apparent prediction accuracy. This suggests
      that care should be taken to compare methods by the same reduction method. Two
      new sequence datasets (CB513 and CB251) are derived which are suitable for cross
      validation of secondary structure prediction methods without artifacts due to
      internal homology. A fully automatic World Wide Web service that predicts protein
      secondary structure by a combination of methods is available via
      http://barton.ebi.ac.uk/.

PMID- 10081964
TI  - Conformational and functional variability supported by the BPTI fold: solution
      structure of the Ca2+ channel blocker calcicludine.
AB  - Calcicludine, a 60-amino acid protein isolated from the green mamba venom, has
      been recently identified as blocking a large set (i.e., L-, N- and P-type) of
      Ca2+ channels. The three-dimensional structure of calcicludine has been
      determined by NMR and molecular modeling using a data set of 723 unambiguous and
      265 ambiguous distance restraints, as 33 phi and 13 chi1 dihedral angle
      restraints. Analysis of the 15 final structures (backbone root-mean-square
      deviation = 0.6 A) shows that calcicludine adopts the Kunitz-type protease
      inhibitor fold. Its three-dimensional structure is similar to that of snake K+
      channel blockers dendrotoxins. Conformational differences with protease
      inhibitors and dendrotoxins are localized in the 3(10) helix and loop 1 (segments
      1-7 and 10-19), the extremity of the beta-hairpin (segment 27-30), and loop 2
      (segment 39-44). These regions correspond to the functional sites of bovine
      pancreatic trypsin inhibitor (BPTI) and dendrotoxins. The positioning of the N
      terminal segment 1-7 relative to the rest of the protein is characteristic of
      calcicludine. The involvement of this segment and the positively charged K31 at
      the tip of the beta-hairpin in the biological activity of calcicludine is
      discussed.

PMID- 10081965
TI  - Characterization of internal motions of Escherichia coli ribonuclease H by Monte
      Carlo simulation.
AB  - The backbone dynamics of Escherichia coli ribonuclease H (RNase H) is studied by
      a recently developed off-lattice Monte Carlo/Metropolis simulation technique. A
      low-resolution model (virtual-bond model) is used together with knowledge-based
      potentials. The calculated mean-square fluctuations in alpha carbons are in good
      agreement with crystallographic temperature factors. The conformations generated
      around the native state are analyzed by time-dependent orientational and
      conformational correlation functions to study the internal motions of RNase at
      different time windows. A correlation between the free-energy changes for native
      state hydrogen exchange (HX) and the extent of the autocorrelation in the
      rotations of the virtual bonds at long times has been observed. Cross
      correlations between the rotations of the bonds, which are near-neighbor in the
      sequence, are effective in all time windows and help the secondary structures to
      preserve their kinetic stability. On the other hand, the existence of cross
      correlations at long times help the tertiary contacts be maintained. The order
      parameter of NH bond vector for each residue has been calculated and compared
      with 15N-NMR relaxation measurements.

PMID- 10081966
TI  - Reciprocal connections between the preglomerular complex and the dorsolateral
      telencephalon in the weakly electric fish, Gymnotus carapo.
AB  - The diencephalic preglomerular complex of gymnotiform fish receives inputs from
      several sensory areas. By employing anterograde and retrograde tracing
      techniques, we studied the afferent and efferent connections of the dorsolateral
      area (dorsal subdivision) of the telencephalon with the preglomerular nuclei in
      the weakly electric fish, Gymnotus carapo. Neurons of the medial preglomerular
      nucleus project to intermediate and deep portions of the middle (commissural)
      level of the dorsolateral telencephalon, and neurons located in the lateral
      preglomerular nucleus project to superficial portions of the middle levels of the
      dorsolateral telencephalon. Therefore, we observed a spatial distribution pattern
      of connectivity between dorsolateral telencephalon and preglomerular complex.

PMID- 10081967
TI  - Activation of the insular and opercular regions of the monkey by drinking as
      revealed by positron emission tomography.
AB  - We measured the regional cerebral blood flow (rCBF) of the monkey using positron
      emission tomography (PET) in the following conditions: self-initiated (SELF),
      visually-initiated (VISUAL), and color-discriminating go/no-go (GONOGO) hand
      movement tasks with reward of water, free reward condition (REWARD), and resting
      states (REST). The insulae, frontal opercula, and mouth sensorimotor area were
      activated in any of SELF, VISUAL, GONOGO, and REWARD, when compared with REST.
      These findings suggest that the insular and opercular regions play an important
      role in the neural processes involved in drinking.

PMID- 10081968
TI  - Relationship between central and peripheral serotonin 5-HT2A receptors: a
      positron emission tomography study in healthy individuals.
AB  - 5-HT2A receptors on platelet membranes are often measured as indirect markers of
      the central 5-HT2A receptors. However, the 5-HT2A receptors on the platelets and
      those in the brain have never been assessed simultaneously in humans. The purpose
      of this study was to evaluate the relationship between platelet membrane and
      neocortical 5-HT2A receptors measured simultaneously in normal healthy
      volunteers. Twelve healthy volunteers had the 5-HT2A receptors on their platelet
      membranes assessed in vitro using [3H]lysergic acid diethylamide ([3H]LSD) and
      their central 5-HT2A receptors measured in vivo using [18F]setoperone and
      positron emission tomography (PET) imaging. We find no significant correlation
      between the binding potential (Bmax/Kd) of 5-HT2A receptors on platelets and in
      brain in the same individual (F1,10 = 0.7, P = 0.42). The study was limited by a
      small sample and the fact the two different ligands were used (i.e. LSD for
      platelets and setoperone for brain); nonetheless, the findings suggest that
      changes in platelet 5-HT2A receptors may not indicate similar changes in central
      5-HT2A receptors.

PMID- 10081969
TI  - Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's beta
      amyloid precursor protein.
AB  - We report the cDNA sequence of human Fe65L2. The human Fe65L2 encoded 486 amino
      acids; the deduced amino acid sequence was shorter by 18 amino acids than the rat
      protein and had 86% identity to the rat protein Three protein-protein interaction
      domains, a WW and two PID/PTB elements, were conserved among the Fe65 protein
      family. Human Fe65L2 mRNA was expressed in various tissues; a transcript of about
      2.2 kb was mainly expressed in the brain. A splicing variant lacking two amino
      acids in the first PID/PTB element was detected. We also confirmed that the
      carboxyl-terminal region of PID/PTB of the Fe65L2 interacted with the
      intracellular domain of the Alzheimer's beta-amyloid precursor protein (APP) and
      APP-like proteins.

PMID- 10081970
TI  - Strain-dependent effects of supraspinal orphanin FQ/nociceptin on thermal
      nociceptive sensitivity in mice.
AB  - Despite much study since its discovery in 1995, the effects of orphanin
      FQ/nociceptin (OFQ/N), the endogenous ligand of the 'orphan' opioid receptor, on
      nociceptive sensitivity remain unclear. Different laboratories have variously
      reported hyperalgesic, analgesic, anti-analgesic or no effect of the peptide on
      thermal assays following supraspinal injection in rodents. We and others have
      argued previously that methodological inconsistencies and experimental parameters
      may explain some of the contradictions in the literature, especially in mice
      where intracerebroventricular (i.c.v.) injections proceed directly through the
      skull. We report presently that both the magnitude of stress-induced analgesia
      (SIA) produced by such i.c.v. injections, and the ability of OFQ/N to antagonize
      this opioid-mediated SIA, are strain-dependent. Specifically, significant
      injection-related SIA was observed in four of six strains studied (outbred: CD-1,
      SW; inbred: AKR/J, BALB/cJ, C3H/HeJ, CBA/J) on the 47.5 degrees C tail-withdrawal
      assay, and OFQ/N blocked this SIA in two strains. These data suggest that genetic
      variability among subject populations may underlie the inconsistent findings
      among researchers, and may in addition provide a promising avenue for future
      study of this novel neuromodulator.

PMID- 10081971
TI  - Peripheral projections of primary sensory neurons immunoreactive for brain
      derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) is synthesized in a subpopulation of
      primary sensory neurons and transported anterogradely to the spinal cord and
      peripheral targets. In the present study, the peripheral projection of sensory
      neurons immunoreactive (-ir) for BDNF was examined by a combined method of
      immunohistochemistry and retrograde tracing in rats. It was found that 36.3% of
      sensory neurons projecting to subcutaneous tissues, 9.8% to epidermis and 8.3% to
      muscle, contained BDNF immunoreactivity. In contrast, only 0.2% of sensory
      neurons projecting to adrenal gland and 0.9% to coeliac ganglia contained BDNF. A
      small proportion of sensory neurons projecting to muscles, mesenteric blood
      vessels and hair follicles was also BDNF immunoreactive. These results provide
      evidence that primary sensory neurons immunoreactive for BDNF project mainly to
      subcutaneous tissues but not to autonomic ganglia and their adjacent viscera.

PMID- 10081972
TI  - The evidence for tonic GABAergic regulation of basal L-DOPA release via
      activation of inhibitory GABA(A) receptors in the nucleus tractus solitarii of
      anesthetized rats.
AB  - We have proposed that DOPA is a neurotransmitter of the primary baroreceptor
      afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a
      putative inhibitory neuromodulator for baroreflex inputs in the NTS. Thus, GABA
      may inhibit DOPAergic transmission in the NTS. We tried to clarify whether basal
      DOPA release is inhibited by muscimol, a GABA(A) agonist, and facilitated by
      bicuculline, a GABA(A) antagonist, during microdialysis of the NTS in
      anesthetized rats. DOPA release was consistently detectable. Muscimol 10-100
      microM perfused via probes gradually inhibited concentration-dependently DOPA
      release. Peak 30% inhibition occurred 2 h after perfusion. Muscimol (30 microM)
      induced inhibition was antagonized by non-effective 10 microM bicuculline.
      Bicuculline (30 microM) elicited peak 30% facilitation of DOPA release 2 h after
      perfusion. Endogenous GABA seems to regulate tonically basal DOPA release via
      activation of inhibitory GABA(A) receptors in the rat NTS. These findings further
      support the above proposal.

PMID- 10081973
TI  - Resetting the rat circadian clock by ultra-short light flashes.
AB  - We examined the effects that ultra-brief, intense, light flashes have on the rat
      circadian clock, the suprachiasmatic nucleus of the hypothalamus (SCN). We found
      that as few as five intense flashes, each 10-micros in duration (1 per s), can
      produce both phase shifts in free-running activity rhythms and Fos expression in
      the SCN in rats kept in constant darkness. After pre-exposure to such flashes,
      phase shifts in response to a continuous light pulse delivered 2 h later were
      potentiated, but Fos expression in the SCN was decreased as following pre
      exposure to continuous light. These results show that flashes induce behavioral
      and cellular effects indicative of clock resetting similar to those induced by
      light stimuli of longer duration. Extremely brief but intense, light stimuli may
      be much more important to clock resetting than had been previously known.

PMID- 10081974
TI  - Neuronal and non-neuronal Trk neurotrophin receptor-like proteins in Eisenia
      foetida (Annelida Oligochaeta).
AB  - The occurrence and distribution of Trk proteins, which are the high-affinity
      signal-transducing receptors for neurotrophins, have been investigated in
      earthworms (Eisenia foetida) using polyclonal antibodies which map within their
      catalytic domain. Western-blot analysis identified major protein bands whose
      estimated molecular masses were consistent with those of the full-length Trk
      proteins in vertebrates. Specific immunoreactivity for TrkA-, TrkB-, and TrkC
      like was observed in neuronal populations of the dorsal cerebral, subpharyngeal
      and ventral cord ganglia. Furthermore, TrkA-like immunoreactivity was observed in
      subcutaneous neurons and nerve fibers between muscle layers in the peripheral
      nervous system. TrkB- and TrkC-like immunoreactivity was observed in the gut
      innervation. Non-neuronal expression of TrkB and TrkC proteins was found in
      epidermal cells, and TrkC-like immunoreactivity was detected in the gut
      epithelium.

PMID- 10081975
TI  - Reduction of depressive-like behavior in mice lacking angiotensinogen.
AB  - We made use of targeted disruption of the mouse angiotensinogen (ATN) gene to
      examine the functional role of the ATN in the central nervous system. Both male
      and female ATN-deficient mice displayed the reduction of depressive-like behavior
      in the behavioral despair swim tests and spontaneous locomotor activity
      diminished. However, both male and female ATN-deficient mice showed no anxiogenic
      like or memory-deficit behavior and there was no change in the pain threshold. We
      propose that endogenous ATN in the central nervous system may regulate the
      depressant state in the brain.

PMID- 10081976
TI  - Effects of an interleukin-1beta analogue [Lys-D-Pro-Thr], on incomplete cerebral
      ischemia-induced inhibition of long-term potentiation in rat hippocampal neurons
      in vivo.
AB  - Although interleukin-1beta (IL-1beta) has recently been implicated in neuronal
      cell death in vitro and in vivo after global forebrain ischemia, the role of IL
      1beta in the functional injuries, i.e. impairment of synaptic transmission, after
      cerebral ischemia that does not cause neuronal death in the nervous system
      remains unknown. To address this question, we investigated the effect of short
      term incomplete ischemia without apparent neural death on hippocampal long-term
      potentiation (LTP) in anesthetized rats, and examined the possible role of IL
      1beta as an intermediary in this effect. Short-term incomplete cerebral ischemia
      (10 min) was induced in halothane-anesthetized rats by bilaterally clamping the
      common carotid arteries. Four days after ischemia, functional injuries in
      neuronal transmission in the hippocampal formation were observed without
      significant changes in pathological studies such as neuronal cell death. The LTP
      elicited in both Shaffer-CA1 synapses and perforant path-dentate gyrus synapses
      was significantly inhibited by the short-term incomplete ischemia. This
      inhibition of LTP was blocked by IL-1beta tripeptide antagonist (Lys-D-Pro-Thr),
      suggesting that the inhibitory effect of mild ischemia on synaptic potentials and
      LTP may be mediated by the generation of IL-1beta. These findings have important
      implications for the role of IL-1beta in not only neuronal cell death but also
      functional injuries without cell loss, perhaps elicited by transient cerebral
      ischemia.

PMID- 10081977
TI  - Evidence that the neuronal nitric oxide synthase inhibitor 7-nitroindazole
      inhibits monoamine oxidase in the rat: in vivo effects on extracellular striatal
      dopamine and 3,4-dihydroxyphenylacetic acid.
AB  - The present study investigated in vivo the kinetics of the changes in rat
      striatal extracellular concentrations of dopamine (DA), and its monoamine oxidase
      (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), following
      administration either of nitric oxide (NO) synthase inhibitors 7-nitroindazole (7
      NI) and N(omega)-nitro-L-arginine methyl ester (L-NAME) or of the widely used MAO
      inhibitor pargyline. DA and DOPAC concentrations were determined every 4 min by
      microdialysis combined with capillary zone electrophoresis coupled with laser
      induced fluorescence detection (CZE-LIFD) and by differential normal pulse
      voltammetry (DNPV), respectively. Administration of 7-NI, both systemic (30
      mg/kg, i.p.) or intrastriatal (1 mM through the microdialysis probe), as well as
      administration of pargyline (75 mg/kg, i.p.), induced simultaneously in the
      striatum a significant increase in extracellular DA and a significant decrease in
      extracellular DOPAC. On the other hand, administration of L-NAME (200 mg/kg,
      i.p.) produced a significant increase in striatal extracellular DA without
      changes in extracellular DOPAC. These data suggest a possible MAO inhibitory
      effect of 7-NI which seems to be restricted to this NOS inhibitor. These results
      may be of special interest for the studies on the functional role of NO in the
      brain, particularly in dopaminergic transmission.

PMID- 10081978
TI  - Alterations in neurokinin A-, substance P- and calcitonin gene-related peptide
      immunoreactivities in the caudal trigeminal nucleus of the rat following
      electrical stimulation of the trigeminal ganglion.
AB  - We have carried out an immunohistochemical study on the presence of neurokinin A
      (NKA) and substance P (SP) in the rat caudal trigeminal nucleus (CTN) after
      electrical stimulation of the trigeminal ganglion (TG), used as an experimental
      model to induce alterations, some of which may occur during migraine attacks
      (release of vasoactive peptides from perivascular trigeminal axons and neurogenic
      inflammation). Both unilateral, 30 min electrical stimulation (5 Hz, 5 ms, 0.1-1
      mA) of the TG and 5 min stimulation with a slight increase in the stimulating
      parameters (7.5 Hz, 5 ms, 1.4 mA) caused a significant depletion of the NKA and
      SP immunoreactivities (-IR) of the TG nerve central terminals in the ipsilateral
      CTN. Calcitonin gene-related peptide (CGRP)-IR of the ipsilateral CTN was also
      studied in the CTN using the increased stimulating parameters and a marked
      depletion of CGRP-IR was also observed following TG stimulation. Such depletion
      may be due to the release of neuropeptides from the trigeminal central terminals.
      These findings suggest that NKA, SP and CGRP could act as neurotransmitters at
      the first central synapses of the trigeminal nociceptive pathway to transmit the
      sensory stimuli to the higher brain centers.

PMID- 10081979
TI  - Chronic amitriptyline administration increases serotonin transporter binding
      sites in the hippocampus of aged rats.
AB  - The effects of ageing and of chronic antidepressant treatment upon 5-HT
      transporter sites ([3H]paroxetine binding) in the rat hippocampus was examined.
      [3H]paroxetine binding to transporter sites was decreased with ageing in the
      hippocampus of control rats (38% decrease in dentate gyrus and CA4).
      Amitriptyline (10 mg/kg, i.p.) had no significant effect on [3H]paroxetine
      binding in 10 months old rats, but increased binding sites in 24 months rats in
      all hippocampal subregions (greatest increase of 109% in CA1 compared to saline
      controls). These data indicate an age-related decrease in hippocampal serotonin
      transporter sites and upregulation of these sites following 10 weeks of
      amitriptyline. The observed increase in transporter sites following amitriptyline
      may contribute to the general lower effectiveness of tricyclic antidepressants
      with ageing.

PMID- 10081980
TI  - Genetic polymorphism in the persyn (gamma-synuclein) gene and the risk of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex disease with the possible involvement of
      several genes. Genetic studies on sporadic late-onset AD have determined APOE*4
      to be the major risk factor. Members of the synuclein gene family are potential
      candidates for the risk of AD. The persyn gene (gamma-synuclein) has recently
      been characterized and a common polymorphism (Glu110Val) has been identified. In
      this study we investigated the association of this polymorphism with sporadic
      late-onset AD patients. We screened DNA samples of 313 late-onset cases and 352
      controls. No significant association was observed between the missense mutation
      and AD. When the data were stratified by APOE*4 carriers and non-APOE*4 carriers,
      no difference was seen for the Glu110Val polymorphism. There was also no
      difference in genotype or allele frequency when stratified by the ACT*A allele.
      Although our data show no effect of this persyn polymorphism in AD,
      characterization of additional polymorphisms in this gene may provide more
      conclusive answers.

PMID- 10081981
TI  - Expression of adenosine A2a receptors gene in the olfactory bulb and spinal cord
      of rat and mouse.
AB  - The expression of adenosine A2a receptors (A2aR) in the mammalian striatum is
      well known. In contrast the exact distribution of A2aR in other regions of the
      central nervous system remains unclear. The aim of this study was to investigate
      the A2aR gene expression in the rat olfactory bulb and spinal cord, two regions
      which are seldom included in mapping studies. Secondly, we compared the A2aR
      expression in the rat and in the mouse brain. Hybridization histochemistry was
      performed with an S35-labelled radioactive oligonucleotide probe. The results
      show strong expression of A2aR in the mouse and rat striatum in accordance with
      previous reports. In the olfactory bulb a weak but specific expression of A2aR
      was found in the granular cell layer in both species. In contrast, no significant
      expression of the A2aR gene was observed in other parts of the brain or the rat
      spinal cord. The presence of the A2aR in the mammalian olfactory bulb suggests a
      functional role for this receptor in olfaction.

PMID- 10081982
TI  - Affinity reagents for cross-linking hemoglobin:
      bis(phenoxycarbonylethyl)phosphinic acid (BPCEP) and bis(3
      nitrophenoxycarbonylethyl)phosphinic acid (BNCEP).
AB  - Synthesis and properties of two new macrobiomolecular cross-linking reagents,
      bis(phenoxycarbonylethyl) phosphinic acid (BPCEP) and bis(3
      nitrophenoxycarbonylethyl)phosphinic acid (BNCEP), have been reported. The
      reagents were successfully employed to cross-link human hemoglobin under
      oxygenated conditions. The sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and
      fast protein liquid chromatography (FPLC) analyses of the reaction products
      indicated that the cross-link was intramolecular in nature, and that it was
      between the two beta subunits of hemoglobin in each case. The products were
      purified by DEAE-cellulose chromatography, and the purified material was employed
      for oxygen-binding assessments. The oxygen equilibrium curve of the cross-linked
      material, in each case, was right-shifted toward lower oxygen affinity as
      desired. The sigmoidal shapes of oxygen curves, in each case, suggested
      retainment of oxygen-binding cooperativity, although considerably lower than that
      of the native hemoglobin

PMID- 10081983
TI  - Two hemoglobin variants with an alteration of the oxygen-linked chloride binding:
      Hb Antananarivo [alpha1(NA1)Val-->Gly] and Hb Barbizon [beta144(HC1)Lys-->Met].
AB  - We here report two new, clinically silent, hemoglobin variants in which the
      structural modification disturbs the oxygen-linked chloride binding. Hb
      Antananarivo [alpha1(NA1)Val-->Gly] was found during a systematic hematological
      study in a 24-year-old woman, who originates from Madagascar. Hb Barbizon
      [beta144 (HC1)Lys-Met] was found in several members of a French family. The
      oxygen binding properties of Hb Barbizon were similar to those of Hb Antananarivo
      showing, in vitro, a decreased chloride effect as compared to Hb A. In Hb
      Barbizon, the replacement of lysine beta144 by a methionine residue decreased
      from 4 to 2 the excess positive charges in the central cavity, thus leading to a
      reduction of about half of the chloride effect. For Hb Antananarivo, the
      mechanism is unclear since there is no difference in the number of positive
      charges in the central cavity but alterations are likely at the alpha1alpha2
      interface.

PMID- 10081984
TI  - The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is
      responsible for hemolytic disease in the newborn of a Sudanese family.
AB  - The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was
      identified by isoelectrofocusing, high performance liquid chromatography, and
      peptide mapping in a mother and two male children of a Sudanese family. All three
      were heterozygous for the abnormal hemoglobin; the father and a third male child
      did not carry the mutation. The mother was also homozygous for two putative
      gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at
      IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated
      region (-A) at position -6 from the polyadenylation site. The father had normal
      gamma genes. All three children were heterozygous for both the gamma+-thalassemia
      mutations. The two older children, who were compound heterozygotes for Hb
      Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice
      which necessitated exchange blood transfusions. Other causes of neonatal jaundice
      were excluded. The third male child, who did not carry the Hb Khartoum anomaly
      but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice.
      It is concluded that the instability of Hb Khartoum in combination with gamma+
      thalassemia is responsible for neonatal hemolytic anemia in this family.

PMID- 10081985
TI  - Southeast Asian ovalocytosis in White persons.
AB  - We describe two White persons, a girl and her mother, presenting with Southeast
      Asian ovalocytosis. The child was evaluated for scoliosis. The red cell indices
      were normal but the cell counter triggered an alarm due to a high fraction of
      hyperdense red cells. Blood smears showed ovalocytes and ovalostomatocytes. Red
      cells exhibited a total lack of deformability upon osmotic gradient ektacytometry
      performed immediately after blood drawing. Analysis of nucleic acids and proteins
      ascertained a 27 nucleotide deletion, resulting in the loss of amino acids 400 to
      408, and the presence in cis of the Memphis I polymorphism. The sulfate transport
      was diminished by more than 50%. There was no acidosis. In vitro invasion of
      ovalocytes by Plasmodium falciparum was decreased. The mother presented with the
      same hematological picture. On the whole, the condition was Southeast Asian
      ovalocytosis in all respects. The present kindred had ancestors who had inhabited
      islands in the Southwestern Indian Ocean.

PMID- 10081986
TI  - Genetic studies suggest a multicentric origin for Hb G-Coushatta [beta22(B4)Glu-
      >Ala].
AB  - Hb G-Coushatta [beta22(B4)Glu-->Ala] is found in geographically separated ethnic
      groups. Commonest along the Silk Road region of China but also present in the
      North American Coushatta, we sought to determine whether this variant had a
      unicentric or multicentric origin. We examined the haplotype of the beta-globin
      gene cluster in two Chinese families and in five Louisiana Coushatta heterozygous
      for this mutation. Chinese and Louisiana Coushatta had different haplotypes
      associated with the identical Hb G mutation. These haplotypes were defined by the
      presence of a HindIII restriction site in the Agamma-globin gene and AvaII
      restriction site in the beta-globin gene in Chinese subjects and their absence in
      the Louisiana Coushatta. We found a CAC at codon beta2 (beta-globin gene
      framework 1 or 2) linked to the Hb G-Coushatta gene in Chinese, and a CAT
      (framework 3) in Louisiana Coushatta, indicating different beta-globin gene
      frameworks. Both the Hb G-Coushatta mutation (GAA-->GCA) and the codon 2 CAC-
      >CAT polymorphism are normal delta-globin gene sequences, suggesting the
      possibility of gene conversion. We conclude that Hb G-Coushatta had at least two
      independent origins. This could be due to separate mutations at codon beta22 in
      Chinese and Louisiana Coushatta, a mutation at this codon and a beta-->delta
      conversion, or two beta-->delta gene conversion events.

PMID- 10081987
TI  - Hb G-Coushatta [beta22(B4)Glu-->Ala] in Thailand.

PMID- 10081988
TI  - Characterization of Hb Djelfa [beta98(FG5)Val-->Ala]] by DNA sequencing in a
      French Caucasian family.

PMID- 10081989
TI  - Heterogeneity of four beta-thalassemia mutations in Greece.

PMID- 10081990
TI  - Hb Schlierbach or beta108(G10)Asn-->Ile: a new variant with low oxygen affinity
      detected in a Swiss family.

PMID- 10081991
TI  - Hb Brent [beta117(G19)His-->Asn]: a new hemoglobin variant found during routine
      antenatal screening.

PMID- 10081992
TI  - A comparison of parenteral and enteral feeding in neonatal piglets, including an
      assessment of the utilization of a glutamine-rich, pediatric elemental diet.
AB  - BACKGROUND: The amino acid requirement profile for infants is different than that
      for adults and needs to be established; this profile also is different for
      infants receiving total parenteral nutrition. We used the neonatal piglet as a
      model for the infant to address (1) the metabolic and physiologic changes due to
      route of feeding and (2) the adequacy of the amino acid pattern in a pediatric
      elemental diet. METHODS: Diets differed only in their amino acid pattern
      (modified human milk [MHM] and a commercial pediatric elemental diet [PED]) and
      were fed continuously for 8 days. Control piglets were fed MHM diet via gastric
      catheters (IG) and were compared with pigs fed MHM diet via venous catheters (IV)
      or to pigs IG-fed PED. RESULTS: MHM-IV piglets experienced enlarged livers and
      gut atrophy, and lower nitrogen retention and body protein content. Higher
      glutamine (and lower glutamate) in PED-IG, compared with MHM-IG, produced no
      apparent advantage with respect to gut growth or histology. Proline, histidine,
      and lysine may have been limiting, and isoleucine and valine excessive, in the
      PED-IG diet as indicated by plasma concentrations, compared with sow-fed piglets;
      however, imbalances in the amino acid profile were not excessive because nitrogen
      retention was not different between MHM-IG or PED-IG pigs. CONCLUSIONS:
      Therefore, the amino acid profile of MHM needs to be modified to improve nitrogen
      retention during parenteral feeding and the profile of oral PED could be improved
      to normalize plasma amino acid concentrations.

PMID- 10081993
TI  - Effect of i.v. amino acids on satiety in humans.
AB  - BACKGROUND: Parenteral nutrients suppress oral food intake. Separate i.v.
      infusion of amino acids (IVAA) at high doses affects gastrointestinal motility
      and secretion. However, little is known on the effects of separate i.v. infusion
      of amino acids at these high doses on satiety. Therefore, we have studied the
      effect of two different doses of a commercially available mixed amino acids
      solution on satiety and food intake. METHODS: Six healthy volunteers (ages 20 to
      34 years) were studied on three separate occasions in random order during (a)
      i.v. saline (control), (b) low-dose IVAA ([LDA] 125 mg protein/kg/h, Vamin 18EF;
      Kabi Pharmacia BV, Woerden, The Netherlands), or (c) high-dose IVAA ([HDA] 250 mg
      protein/kg/h) for 360 minutes. Subjective criteria such as wish to eat,
      prospective feeding intentions, and feelings of hunger and fullness were scored
      on 100-mm visual analog scales at 30-minute intervals. Food preference also was
      measured every 60 minutes with food selection lists. At the end of the experiment
      a meal was presented. RESULTS: Feelings of fullness were significantly (p < .05)
      increased during both LDA and HDA. The wish to eat was significantly (p < .05)
      decreased during HDA compared with control and LDA. Prospective feeding
      intentions also tended to be reduced during HDA (not significant). Feelings of
      hunger were not significantly different between the three experiments. Total food
      selection was significantly (p < .05) decreased during LDA and HDA, mainly
      because of a significantly (p < .05) decreased preference for fat-rich items.
      However, the total amount of food consumed at the end of the experiment was not
      significantly different between the three experiments. CONCLUSIONS: The present
      study shows that in healthy volunteers, IVAA (1) increase satiety ratings, (2)
      increase feelings of fullness, (3) decrease preprandial food selection, and (4)
      have no effect on subsequent oral food intake.

PMID- 10081994
TI  - Extracellular water: sodium bromide dilution estimates compared with other
      markers in patients with acquired immunodeficiency syndrome.
AB  - Extracellular fluid and closely related extracellular water (ECW) provide
      information on nutritional status in health and disease. Although various methods
      exist for ECW determination, little is known about their comparability in
      patients with wasting diseases such as acquired immunodeficiency syndrome (AIDS).
      One practical method, the dilution of sodium bromide (NaBr), is used widely in
      clinical research, although its relationship to other ECW markers has not been
      well characterized. The present study sought to compare ECW estimates as
      determined by NaBr and three other methods in 11 male patients with AIDS (mean +/
      SD; age, 44+/-12 years; body weight, 64.5+/-8.8 kg; and height, 172+/-4 cm). ECW
      volumes were determined from NaBr dilution, total body chlorine (TBCl) by delayed
      gamma-neutron activation analysis, total body water (TBW) by tritium dilution
      combined with total body potassium (TBK) by whole body 40K counting, and
      radioactive sulfate dilution (35SO4). All correlations between the NaBr method
      and other methods were statistically significant (NaBr vs TBCl [r = .91; p <
      .001]; vs TBW/TBK [r = .76; p < .01]; and vs 35SO4 [r = .89; p < .001]). As
      expected from previous studies, ECW (L) derived by NaBr provided a group mean
      (15.1+/-2.2 L) similar to the TBCl method (15.4+/-1.7 L; p = .32), a
      significantly smaller ECW than by the TBW/TBK method (18.6+/-3.4 L; p = .0004),
      and a significantly larger ECW than by 35SO4 method (13.3+/-3.0 L; p = .002).
      Estimating ECW by NaBr dilution was comparable with other research-based ECW
      methods and, thus, offers a practical alternative for evaluating ECW in patients
      with AIDS.

PMID- 10081995
TI  - Compatibility of medications with 3-in-1 parenteral nutrition admixtures.
AB  - BACKGROUND: The absence of drug compatibility information with 3-in-1 parenteral
      nutrition admixtures has been problematic. The purpose of this project was to
      evaluate the physical compatibility of 106 selected drugs during simulated Y-site
      injection into nine different 3-in-1 parenteral nutrition admixture formulations.
      METHODS: Four-milliliter samples of each of the representative 3-in-1 parenteral
      nutrition admixture formulations were combined in a 1:1 ratio with 4-mL samples
      of each of 106 drugs, including supportive care drugs, anti-infectives, and
      antineoplastic drugs. Six replicate samples of each combination were prepared.
      Two samples were evaluated initially after mixing, two more after 1 hour, and the
      last two after 4 hours at 23 degrees C. At each test interval, the samples were
      subjected to centrifugation, causing the fat to rise to the top. The top fat
      layer and most of the aqueous phase were removed, and the remaining liquid was
      diluted with about 7 mL of particle-free, high-performance liquid chromatography
      grade water to facilitate observation of any particulates that might have formed.
      Visual examinations were performed in normal diffuse fluorescent laboratory light
      and under high-intensity, monodirectional light. RESULTS: Most of the drugs
      tested were physically compatible with the 3-in-1 parenteral nutrition admixtures
      for 4 hours at 23 degrees C. However, 23 drugs exhibited various
      incompatibilities with one or more of the parenteral nutrition admixtures. Six
      drugs resulted in the formation of precipitate with some or all of the
      admixtures. Seventeen drugs caused disruption of the emulsion, usually with
      oiling out. CONCLUSIONS: Most of the test drugs were physically compatible with
      the nine representative 3-in-1 parenteral nutrition admixtures. However, the 23
      drugs that resulted in incompatibilities should not be administered
      simultaneously with the incompatible parenteral nutrition admixtures via a Y
      injection site.

PMID- 10081996
TI  - Intestinal permeability after early postoperative enteral nutrition in patients
      with upper gastrointestinal malignancy.
AB  - BACKGROUND: Increased intestinal permeability may lead to sepsis in resected
      upper gastrointestinal (GI) cancer patients. This study sought to determine
      whether these patients demonstrated increased intestinal permeability and if
      early postoperative enteral nutrition would alter this result. METHODS: Nineteen
      patients undergoing complete resection of upper GI malignancy were randomized
      into two groups: the nonfed group received IV crystalloid, and the fed group
      started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six
      nonoperative volunteers were controls. The lactulose/mannitol test was performed
      on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine
      was collected for 6 hours. RESULTS: All patients (nonfed, 1.895+/-0.34; fed,
      0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls
      (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward
      control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed,
      0.606+/-0.12, p = .08). CONCLUSIONS: Major upper GI surgery for malignancy
      resulted in a significant increase in intestinal permeability on POD 1. With or
      without enteral nutrition, this measure of intestinal permeability returned to
      normal on POD 5 in well-nourished patients.

PMID- 10081997
TI  - Comparison between dodecanedioic acid and long-chain triglycerides as an energy
      source in liquid formula diets.
AB  - BACKGROUND: Dicarboxylic acids (DA) are water-soluble substances with high-energy
      density proposed as an alternative lipid substrate for nutrition purposes. The
      aim of the present study was to investigate the interaction between glucose and
      DA or long-chain triglyceride (LCT) metabolism after oral administration.
      METHODS: Two test meals containing either dodecanedioic acid (C12, the 12-atom
      DA) or LCT, together with glucose and amino acids, were each administered to five
      healthy volunteers. Tracer amounts of 14C-dodecanedioic acid were added to the
      C12 meal to recover expired traced CO2 and estimate the minimum rate of C12
      oxidation. Glucose, insulin, and C12 plasma levels were measured for 360 minutes
      after the test meal. Indirect calorimetry was performed for the duration of the
      study. RESULTS: LCTs proved ineffective in promoting their own oxidation after
      oral administration. On the contrary, C12 was promptly oxidized, a minimum of
      21.9%+/-8.3% of the administered amount giving rise to the recovered expired CO2.
      This difference in metabolic fate was reflected in a sparing effect on glucose:
      suprabasal respiratory quotient and suprabasal carbohydrate oxidation were
      significantly (p < .05) lower under C12 administration than under LCT
      administration, with a difference of 0.024+/-0.015 in respiratory quotient (RQ)
      and a difference of 0.791+/-0.197 kJ/min in carbohydrate oxidation. In
      particular, carbohydrate oxidation increased by 54% over basal with LCT but only
      by 28% with C12 administration. RQ increased over basal by 5.8% with LCT but only
      by 3.0% with C12 administration. CONCLUSIONS: These results show a fundamental
      metabolic difference between conventional lipids and DAs, which is the basis for
      a possible role of DAs in clinical nutrition. The fate of spared glucose is
      likely to be storage in glycogen form when dodecanedioic acid is made available
      as an energy source.

PMID- 10081998
TI  - Peripherally inserted central catheters for parenteral nutrition: a comparison
      with centrally inserted catheters.
AB  - BACKGROUND: Central venous access is crucial for the provision of adequate
      parenteral nutrition (PN). The type of central venous access device (CVAD) has
      evolved over the past 10 years. The most recent trend has been to use
      peripherally inserted central catheters (PICCs). This development has occurred
      without controlled clinical trials. METHODS: Over a 10-year period, the nutrition
      support service at a single institution has prospectively collected data on CVADs
      used for providing PN. The types of CVAD used for providing PN were analyzed, and
      the major complications associated with CVADs, thrombosis and line sepsis, were
      compared over three different time periods: 1988-1989; 1992-1993; 1996-1997. In
      addition, complications associated with PICCs were compared with other CVADs.
      RESULTS: The following were the dominant CVADs over each of the three time
      periods: 1988-1989: tunneled catheters, 80%; 1992-1993: nontunneled catheters,
      46%; and 1996-1997: PICCs, 48%. There was a decreased incidence of sepsis and
      pneumothorax in 1996-1997 and an increase in severed or leaking catheters and
      phlebitis. In a comparison of PICC and non-PICC catheters over the past 3 years,
      there was a trend toward decreasing sepsis with PICC catheters but an increase in
      malposition, inadvertent removal, and severed or leaking catheters. CONCLUSIONS:
      PICCs have replaced tunneled and nontunneled central catheters as the most
      commonly used CVAD for providing PN. PICCs do not result in increased line sepsis
      or thrombosis but have an increased incidence of local complications such as
      leaking catheters, phlebitis, and malposition.

PMID- 10081999
TI  - Intradialytic parenteral nutrition in malnourished hemodialysis patients: a
      prospective long-term study.
AB  - BACKGROUND: Malnutrition is a frequent problem of patients on intermittent
      hemodialysis and substantially contributes to their morbidity and mortality.
      METHODS: In 26 hemodialysis patients who, despite dietary advice and oral
      nutritional supplements, still had malnutrition, the feasibility and effects of a
      specific intradialytic parenteral nutritional (IPN) regimen were evaluated during
      a 9-month study period. An IPN solution consisting of 250 mL glucose 50%, 250 mL
      lipids 20%, and 250 mL amino acids 7% was infused i.v. three times a week during
      the dialysis session. At the end of each dialysis session an additional volume of
      250 mL amino acids was infused as a rinsing fluid. Insulin was administered i.v.
      before dialysis. RESULTS: Of the 26 enrolled patients, 16 completed the study.
      The remaining 10 patients withdrew mainly because of muscle cramps and nausea
      during the initiation phase of the treatment, when sodium was not present in the
      IPN fluid but was supplemented intermittently. In the 16 treated patients, body
      weight, which had decreased in the pretreatment period from 58.2+/-1.3 kg (-6
      months) to 54.8+/-10.1 kg at the start of the study, increased again up to 57.1+/
      10.7 kg after 9 months IPN (p < .05). Serum transferrin and prealbumin rose from
      1.7+/-0.4 to 2.0+/-0.4 g/L and from 0.23+/-0.05 to 0.27+/-0.10 g/L, respectively.
      Bone densitometry showed an increase of tissue mass, mostly related to a rise in
      fat tissue. Triceps skinfold (p < .05) and arm muscle compartment of the midarm
      (p = .07) increased as well. No such changes were observed in the patients who
      withdrew from treatment. CONCLUSIONS: An i.v. hyperalimentation regimen applied
      to malnourished hemodialysis patients results in a rise of body weight and in a
      limited, but significant, change of some parameters of nutritional status. The
      rise in body weight is at least in part attributable to an increase of body fat,
      without changes in plasma lipid levels.

PMID- 10082000
TI  - Bioimpedance analysis: potential for measuring lower limb skeletal muscle mass.
AB  - BACKGROUND: Ambulation, balance, and lower extremity bone mass and strength are
      all partially dependent on lower limb skeletal muscle mass. At present, both
      research and clinical methods of evaluating lower limb skeletal muscle mass as a
      component of nutrition assessment are limited. One potential simple and
      inexpensive method is lower extremity bioimpedance analysis (BIA). The present
      study had two objectives: to examine the determinants of lower limb resistance,
      with the underlying hypothesis that fluid-containing muscle is the main
      electrical conductor of the lower limbs; and to establish if a correlation of
      equivalent magnitude and similar covariates is observed when height squared (H2)
      is used instead of lower limb length squared (L2) in multiple regression models
      relating resistance to independent variables. METHODS: Lower limb resistance was
      measured using a contact-electrode BIA system, and lower limb fat and skeletal
      muscle were estimated by dual-energy x-ray absorptiometry in healthy adults. A
      physical BIA model was developed in the form of a regression equation with path
      length (as L2 and H2)-adjusted resistance as dependent variables and lower limb
      skeletal muscle, fat, age, and gender as potential independent variables.
      RESULTS: There were 94 subjects, 34 men and 60 women, with a mean (-/+SD) age of
      41.5+/-17.8 years. Strong associations were observed between L2/resistance and
      lower limb skeletal muscle, although for both men and women, age entered into the
      model as a significant covariate (total R2, men = .79 and women = .72; both p <
      .001). Similar models were observed with H2/resistance as dependent variable.
      Additional analyses showed a significantly lower resistance in lower limb
      skeletal muscle and height-matched old vs young subjects. CONCLUSIONS: Strong
      associations exist between measured lower limb resistance and lower limb muscle
      mass, adjusting for electrical path length either by L2 or H2. These observations
      suggest the potential of predicting skeletal muscle using BIA-measured lower limb
      resistance adjusted for stature. Age is also an independent variable in lower
      limb resistance-skeletal muscle associations, suggesting the need to establish
      underlying mechanisms of age-related resistance effects and to consider subject
      age when developing BIA prediction models.

PMID- 10082001
TI  - Protecting solutions of parenteral nutrition from peroxidation.
AB  - BACKGROUND: Light exposure induces the generation of peroxides in solutions of
      total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell,
      in tissue, and in isolated organs. To decrease the infused peroxide load and to
      protect the quality of the parenteral nutrients, we tested the photoprotective
      properties of different infusion sets. METHODS: Solutions of fat-free TPN and all
      in-one total nutrient admixture (TNA) were run through sets of bags (clear and
      covered) and tubings (clear and colored: black, orange, and yellow) offering
      different levels of protection against light. Peroxide levels were determined by
      ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2
      nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. RESULTS:
      Protection of only the bag had little effect on peroxide generation. In fat-free
      TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times
      higher when run through clear compared with colored tubings. When exposed to
      phototherapy or in the presence of lipids, peroxides were two to three times
      higher with the clear compared with the black tubing; meanwhile, orange and
      yellow tubings offered varying levels of protection related to their light
      absorbing properties. Colored tubings offered a greater protection against the
      disappearance of thiol functions. CONCLUSIONS: Covering bags and using orange and
      yellow tubings may be a practical solution to reduce infused peroxide loads from
      about 400 to 100 microM. This is especially relevant in patients with an immature
      or a compromised antioxidant capacity or when phototherapy or preparations of TNA
      are used.

PMID- 10082002
TI  - Metabolic and monetary costs of avoidable parenteral nutrition use.
AB  - BACKGROUND: We prospectively collected data on in patients receiving parenteral
      nutrition to determine the magnitude of potentially preventable metabolic and
      monetary costs associated with parenteral nutrition. METHODS: Parenteral
      nutrition was prescribed by the treating physicians with optional consultation
      from a multidisciplinary metabolic support service. Days on parenteral nutrition,
      appropriateness of parenteral nutrition, metabolic complications, and avoidable
      parenteral nutrition charges were determined. Parenteral nutrition use was
      considered "indicated" or "not indicated" based on the American Society for
      Parenteral and Enteral Nutrition guidelines and "preventable" if the
      gastrointestinal tract was functional but not accessed when possible. RESULTS: Of
      the 209 parenteral nutrition starts, 62% were indicated, 23% were preventable,
      and 15% were not indicated. Parenteral nutrition starts were deemed indicated in
      82% of instances in which a metabolic support service consult was obtained,
      compared with 56% in which a consultation was not obtained (p = .004).
      Hyperglycemia was the most common metabolic complication, with an overall
      incidence of 20%. Metabolic complications occurred less frequently in patients
      who received a metabolic support service consultation compared with patients who
      did not (34% vs 66% of parenteral nutrition days, respectively; p = .004).
      Parenteral nutrition use of < or =5 days duration was significantly less frequent
      among patients who received metabolic support service consultation (16% vs 35%; p
      = .002). Parenteral nutrition that was not indicated or preventable resulted in
      excess annualized patient charges of more than one half million dollars not
      accounting for charges related to treatment of potentially avoidable parenteral
      nutrition complications. CONCLUSIONS: This study illustrates that not-indicated
      and preventable parenteral nutrition initiation, short-term parenteral nutrition
      use, and metabolic complications are less likely when patients receive
      consultation by a multidisciplinary team with expertise in nutrition and
      metabolic support. Furthermore, the avoidance of inappropriate parenteral
      nutrition use translates into substantial cost savings.

PMID- 10082003
TI  - Catabolic consequences of infection and injury: the role of plasma protein
      (albumin) loss.

PMID- 10082004
TI  - The relationship between moral decision making and patterns of consolidation and
      transition in moral judgment development.
AB  - Following models that describe intraindividual correlates of stage transitions
      (S. S. Snyder & D. H. Feldman, 1984), this study assessed the relation between a
      measure of consolidation and transition in moral judgment development and the
      utility of moral concepts in sociomoral decision making. The study extends
      previous research in suggesting that individuals use moral concepts differently
      as they cycle through periods of consolidation and transition. With multiple
      cross-sectional and longitudinal samples, findings indicate that participants'
      reliance on a Kohlbergian moral framework as measured by the Defining Issues Test
      is highest during periods of consolidation and lowest during transitions. As
      participants move into periods of consolidation, the utility of moral stage
      information increases. Thus, this study indicates that the consolidation and
      transition model can be used to help identify individuals who are more or less
      likely to use Kohlberg's moral stages in their moral decision making.

PMID- 10082005
TI  - Predicting adolescent peer problems and antisocial activities: the relative roles
      of aggression and dysregulation.
AB  - This study examined the relative roles of aggression and other dysregulated
      behaviors in the prediction of adolescent peer problems and antisocial behavior.
      The social adjustment of 145 boys studied first in Grades 3-6 was assessed again
      4 years later in Grades 7-10. At each time, peer ratings of aggressive,
      hyperactive-disruptive, withdrawn, and irritable-inattentive behaviors were
      collected. Aggression and withdrawal showed stability and were linked to peer
      difficulties in elementary school and in adolescence, but these behaviors
      indicated significant risk for adolescent rejection, victimization, and
      antisocial activity primarily when accompanied by irritable-inattentive
      behaviors. Results are discussed in terms of the potential role that difficulties
      regulating negative affect may play in the genesis of the particular
      constellation of irritable-inattentive behaviors studied here and the
      developmental significance of aggressive or withdrawn problem profiles that are
      or are not accompanied by these behavioral indicators of dysregulation.

PMID- 10082006
TI  - Guilt, shame, and symptoms in children.
AB  - The authors asked whether evidence could be found for adaptive or maladaptive
      aspects of guilt and shame in 5-12-year-old children (44 boys, 42 girls).
      Children completed semiprojective and scenario-based measures thought to assess
      shame, guilt, or both. Their parents (N = 83) completed the Child Behavior
      Checklist to assess child symptoms. Shame and projective guilt were related to
      symptoms; they also were associated with self-blame and attempts to minimize
      painful feelings. Scenario-based guilt was related to fewer symptoms in boys but
      to greater symptoms in girls. This measure of guilt reflected concerns with
      adhering to standards, expressing empathy, and taking appropriate responsibility.
      Discussion focuses on possible origins of differential symptom-emotion links in
      boys and girls as well as measurement implications.

PMID- 10082007
TI  - Differential impact of preschool models on development and early learning of
      inner-city children: a three-cohort study.
AB  - Three different preschool models operating in an urban school district were
      identified through cluster analysis of teacher responses to the Pre-K Survey of
      Beliefs and Practices. The language, self-help, social, motor, and adaptive
      development, along with mastery of basic skills, of 721 4-year-olds randomly
      selected from these models were compared. Children in the child-initiated model
      demonstrated greater mastery of basic skills than did children in programs in
      which academics were emphasized and skills were taught. Children in the
      combination model did significantly poorer on all measures except self-help and
      development of social coping skills compared with children in either the child
      initiated or academically directed models. Girls outperformed boys in all areas
      except gross motor development and play and leisure skills. Implications for
      educational policymakers are discussed.

PMID- 10082008
TI  - Relational and physical forms of peer victimization in preschool.
AB  - Recent studies of peer victimization have demonstrated the importance of studying
      relational as well as physical forms of peer maltreatment for understanding
      children's social-psychological adjustment problems. Studies in this area have
      been limited thus far by a focus on school-age children (9-12-year-olds). Given
      the significance of early identification of children's social difficulties for
      intervention and prevention efforts, this research was designed to assess
      relational and physical peer victimization among preschool-age children (3-5-year
      olds). Results indicated that boys were significantly more physically victimized
      than girls whereas girls were more relationally victimized. Both relational and
      physical victims experienced greater adjustment problems than did their peers.
      Relational victimization contributed unique information about adjustment beyond
      that provided by physical victimization.

PMID- 10082009
TI  - Social interaction skills and theory of mind in young children.
AB  - Two studies explored relations between peer social skills and theory of mind in
      young children. In Study 1, a global teacher rating of social skills with peers,
      performance on a traditional false-belief task, a standardized assessment of
      auditory language comprehension, and a time sampling of amount of speech with
      peers were obtained. Positive, but moderate, zero-order correlations were
      observed between the false-belief measure and social skills, and false belief
      accounted for a significant amount of additional variance in social skills after
      covarying age and the 2 measures of language. Study 2 replicated the findings of
      Study 1 by using a larger sample and a standardized teacher questionnaire. The
      results are discussed with regard to the critical role of a mentalistic theory of
      behavior for human social interactions.

PMID- 10082010
TI  - "God made me a girl": sex-category constancy judgments and explanations
      revisited.
AB  - To examine reasons for inconsistent findings in the development of sex-category
      constancy, children's constancy judgments and their accompanying explanations
      were studied over a 3-year period. Preschool, kindergarten, and 1st-grade
      children (N = 195) completed a sex-category constancy measure that elicited
      explanations and assessed constancy for the self and others across changes in
      gender-typed clothing, activities, and traits. Improvements in sex-category
      constancy performance were linked to explanations based on operational reasoning.
      Lower constancy scores were linked to explanations that emphasized gender role
      norms and external appearances. A separate analysis revealed that judgment
      explanation relationships were stronger for questions about gender role changes
      in the self as opposed to others and for changes in gender-typed clothing as
      opposed to activities and traits. Findings suggest that the salience and personal
      relevance of gender role changes have important effects on children's sex
      category constancy judgments and explanations.

PMID- 10082011
TI  - Predicting developmental outcomes at school entry using a multiple-risk model:
      four American communities. The Conduct Problems Prevention Research Group.
AB  - The contributions of different risk factors in predicting children's
      psychological and academic outcomes at the end of 1st grade were examined. Using
      a regression model, levels of ecobehavioral risk were assessed in the following
      order: specific demographics, broad demographics, family psychosocial status,
      mother's depressive symptoms, and neighborhood quality. Participants were 337
      families from 4 American communities. Predictor variables were assessed in
      kindergarten, and teacher, parent, and child outcomes (behavioral and academic)
      were assessed at the end of 1st grade. Results indicated that (a) each level of
      analysis contributed to prediction of most outcomes, (b) 18%-29% of the variance
      was predicted in outcomes, (c) a common set of predictors predicted numerous
      outcomes, (d) ethnicity showed little unique prediction, and (e) the quality of
      the neighborhood showed small but unique prediction to externalizing problems.

PMID- 10082012
TI  - Can newborns discriminate between their own cry and the cry of another newborn
      infant?
AB  - Two experiments were conducted to test whether newborns could discriminate
      between their own cry and the cry of another newborn infant. Facial behavior and
      nonnutritive sucking rate were adopted as dependent measures. In Experiment 1, 20
      newborns in an awake state were presented with either their own cry or the cry of
      another infant. In the latter condition, newborns showed the facial expression of
      distress more frequently and for a longer duration. In addition, the rate of
      sucking decreased significantly between the pretest phase and the 1st min of
      presentation of another infant's cry. Newborns' responses, although delayed and
      less intense, showed a similar trend in Experiment 2, during which 20 newborns in
      a sleep state were tested with the same procedure. These results indicate the
      newborns' capability to discriminate between the 2 cry stimuli and show the
      effectiveness of a newborn cry in inducing distress signals in another newborn
      infant.

PMID- 10082013
TI  - The drawbridge phenomenon: representational reasoning or perceptual preference?
AB  - Two experiments investigated whether infants would look longer at a rotating
      "drawbridge" that appeared to violate physical laws because they knew that it was
      causally impossible, as claimed by R. Baillargeon, E. S. Spelke, and S. Wasserman
      (1985) and R. Baillargeon (1987a). Using a habituation paradigm, they reported
      that infants looked longer at a display that appeared impossible (rotated 180
      degrees while an obstructing box was behind it) than at one that appeared
      possible (rotated only 112 degrees, appearing to stop at the box). Experiment 1
      eliminated habituation to 180 degree screen rotations. Still, infants looked
      longer at the 180 degree impossible rotations. Critically, however, infants also
      looked longer at possible 180 degree rotations in Experiment 2, in which no
      obstruction was present. Moreover, no difference in effect size was found between
      the 2 experiments. These findings indicate that infants' longer looking at 180
      degree rotations is due to simple perceptual preference for more motion. They
      question R. Baillargeon's (1987a) claim that it is due to infants'
      representational reasoning about physically impossible object permanence events.

PMID- 10082014
TI  - Multiple attachment relationships within families: mothers and fathers with two
      young children.
AB  - Security of attachment between mothers and fathers and their 2 children was
      examined in 41 maritally intact families. Strange Situation assessments of
      attachment security for the younger children (mean age = 1 year 10 months),
      Attachment Q-sort ratings of the older children (mean age = 4 years 8 months),
      and ratings of parental caregiving behavior of both children were obtained.
      Younger and older children developed concordant attachments to both parents.
      Parents were consistent in their caregiving behavior toward their 2 children.
      However, parents were not congruent in their attachment to their 2 children.
      Associations were found between maternal caregiving and attachment only in the
      younger group. The results support the idea that parental caregiving behavior
      accounts for only modest portions of the variance in attachment security;
      evolving attachments integrate developmental inputs from the children and the
      caregivers in the network of early family relationships.

PMID- 10082015
TI  - Short-term and long-term effects of early parental employment on children of the
      National Longitudinal Survey of Youth.
AB  - This study examined the effects of early parental employment on children in the
      National Longitudinal Survey of Youth. Minimal effects on children's later
      functioning were found. Early maternal employment status and the timing and
      continuity of early maternal employment were not consistently related to
      children's development. Working more hours was associated with slightly lower
      cognitive development through age 9 and slightly lower academic achievement
      scores before age 7 but had no significant relation to children's behavior
      problems, compliance, or self-esteem. Early parental employment appeared to be
      somewhat more beneficial for single mothers and lower income families. There was
      some support for the hypothesis that early parental employment positively affects
      children's development by increasing family income.

PMID- 10082016
TI  - Effect of maltreatment on preschoolers' narrative representations of responses to
      relieve distress and of role reversal.
AB  - A total of 80 low-socioeconomic status maltreated preschoolers were contrasted
      with 27 nonmaltreated preschoolers on their narrative representations. The
      children completed story stems, taken from the MacArthur Story-Stem Battery
      (MSSB; I. Bretherton, D. Oppenheim, H. Buchsbaum, R. N. Emde, & the MacArthur
      Narrative Group, 1990), that introduced stressful family situations. Using the
      MacArthur narrative coding manual (J. Robinson, L. Mantz-Simmons, J. Macfie, &
      the MacArthur Narrative Group, 1992), coders rated portrayals of parental and
      child character responses, as well as participant responses, to relieve
      children's distress. They also rated role reversal (children caretaking their
      parents) from the narrative emotion coding manual (S. L. Warren, L. Mantz
      Simmons, & R. N. Emde, 1993). Maltreated preschoolers portrayed parents and
      children as responding less often--yet themselves as stepping into the story more
      often to relieve children's distress--than did nonmaltreated preschoolers. Abused
      children (sexually, physically, or both) portrayed the most participant
      responses, and neglected children (with no abuse) portrayed the fewest child
      responses. Role reversal was associated with physical abuse.

PMID- 10082017
TI  - Age differences in personality across the adult life span: parallels in five
      cultures.
AB  - Both cross-sectional and longitudinal studies in the United States have shown
      consistent changes between college age and middle adulthood. There appear to be
      declines in 3 of the 5 major factors of personality--Neuroticism, Extraversion,
      and Openness--and increases in Agreeableness and Conscientiousness. To examine
      cross-cultural generalizability of these findings, translations of the Revised
      NEO Personality Inventory were administered to samples in Germany, Italy,
      Portugal, Croatia, and South Korea (N = 7,363). Similar patterns of age
      differences were seen in each country, for both men and women. Common trends were
      also seen for the more specific traits that define the major factors. Because
      these nations differ substantially in culture and recent history, results suggest
      the hypothesis that these are universal maturational changes in adult
      personality.

PMID- 10082018
TI  - Individual moral judgment and cultural ideologies.
AB  - Moral judgment cannot be reduced to cultural ideology, or vice versa. But when
      each construct is measured separately, then combined, the product predicts
      powerfully to moral thinking. In Study 1, 2 churches (N = 96) were selected for
      their differences on religious ideology, political identity, and moral judgment.
      By combining these 3 variables, a multiple correlation of .79 predicted to
      members' moral thinking (opinions on human rights issues). Study 2 replicated
      this finding in a secular sample, with the formula established in Study 1 (R =
      .77). Individual conceptual development in moral judgment and socialization into
      cultural ideology co-occur, simultaneously and reciprocally, in parallel, and not
      serially. Individual development in moral judgment provides the epistemological
      categories for cultural ideology, which in turn influences the course of moral
      judgment, to produce moral thinking (e.g., opinions about abortion, free speech).

PMID- 10082019
TI  - Parental beliefs about managing sibling conflict.
AB  - This study examined the correspondence between parents' beliefs about the most
      effective ways to manage sibling conflict and their responses to their children's
      spontaneous sibling conflicts. Eighty-eight 2-child, 2-parent families
      participated in 3 home sessions. Second-born children were 3-5 years old, and
      firstborn children were 2-4 years older. Parents' use of a particular conflict
      management strategy was based, in part, on their perception of how effective the
      strategy was and how well they could carry out the strategy. For example,
      mothers' use of child-centered strategies was predicted by their belief that
      parental control strategies were ineffective. Fathers' use of control strategies
      was predicted by their low confidence in enacting child-centered techniques.
      Although both mothers and fathers perceived child-centered and control strategies
      as more effective than passive nonintervention, parents engaged in passive
      nonintervention most often.

PMID- 10082020
TI  - Attention and reaction to distress in infancy: a longitudinal study.
AB  - The primary aim of this study was to verify whether early individual differences
      in look duration are related to general mechanisms of the infant nervous system
      that draw together attention and emotion. Thirty-one infants were observed at 3,
      5, and 11 months of age. Facial expressions of pain and distress were observed by
      means of C. Izard's (1979) Maximally Discriminative Facial Movement Coding System
      90 s after routine pediatric vaccinations. Several measures of visual attention
      were taken experimentally in a separate testing session. Significant correlations
      between measures of attention and duration of facial expressions of pain and
      distress were found at each age level. Infants who showed pain or distress for a
      shorter time period also paid attention for a shorter time period and vice versa.
      The main conclusion is that individual differences combining control of both pain
      and attention can be identified from early infancy.

PMID- 10082021
TI  - An event-based analysis of the coordination of early infant vocalizations and
      facial actions.
AB  - This study used an event-based approach to provide empirical evidence regarding
      the nature of coordination in 3- and 6-month-old infants. Vocalizations and
      facial actions of 12 normally developing infants interacting with their
      caregivers were coded. Coded vocalizations and facial actions were considered
      coordinated when they temporally overlapped. Results indicate that infants
      coordinated their vocalizations and facial actions more than expected by chance.
      Coordinated events were governed by 2 sequence patterns. When 2 communicative
      events were temporally associated across modalities, 1 event tended to be
      completely embedded within the other, and vocalizations tended to end before
      facial actions. This study provides new information about how infant
      communication is structured, confirms results from other coordination studies,
      and describes a new method for analysis of event-based data.

PMID- 10082022
TI  - Gesture and early bilingual development.
AB  - The relationship between speech and gestural proficiency was investigated
      longitudinally (from 2 years to 3 years 6 months, at 6-month intervals) in 5
      French-English bilingual boys with varying proficiency in their 2 languages.
      Because of their different levels of proficiency in the 2 languages at the same
      age, these children's data were used to examine the relative contribution of
      language and cognitive development to gestural development. In terms of rate of
      gesture production, rate of gesture production with speech, and meaning of
      gesture and speech, the children used gestures much like adults from 2 years on.
      In contrast, the use of iconic and beat gestures showed differential development
      in the children's 2 languages as a function of mean length of utterance. These
      data suggest that the development of these kinds of gestures may be more closely
      linked to language development than other kinds (such as points). Reasons why
      this might be so are discussed.

PMID- 10082023
TI  - Distinctive messages in infant-directed lullabies and play songs.
AB  - Mothers were recorded singing a song of their choice in both a lullaby style and
      a play-song style to their 6-month-olds. Adult raters identified the play-song
      style and lullaby-style versions with 100% accuracy. Play-song-style renditions
      were rated as being more brilliant, clipped, and rhythmic and as having more
      smiling and more prominent consonants. Lullaby-style renditions were
      characterized as being more airy, smooth, and soothing. Adults observed
      videotapes (without sound) of 6-month-olds listening to alternating lullaby-style
      and play-song-style trials and performed at above chance levels when determining
      which music the infants were hearing. Coding analyses revealed that infants
      focused their attention more toward themselves during lullaby-style trials and
      more toward the external world during play-song-style trials. These results
      suggest that singing may be used to regulate infants' states and to communicate
      emotional information.

PMID- 10082024
TI  - Children's ability to infer utterance veracity from speaker informedness.
AB  - Children between the ages of 3 years 7 months and 6 years 5 months experienced a
      contradiction between what they knew or guessed to be inside a box and what they
      were told by an adult. The authors investigated whether children believed what
      they were told by asking them to make a final judgment about the box's content.
      Children tended to believe utterances from speakers who were better informed than
      they themselves were and to disbelieve those from less well-informed speakers,
      with no age-related differences. This behavior implies an understanding of the
      speaker's knowledge and suggests that children can learn from oral input while
      being appropriately skeptical of its truth. Children also gave explicit knowledge
      judgments on trials on which no utterances were given. Performance on knowledge
      trials was less accurate than, and unrelated to, performance on utterance trials.
      Research on children's developing explicit theory of mind needs to be broadened
      to include behavioral indexes of understanding the mind.

PMID- 10082025
TI  - Parent and child expressed affect and children's social competence: modeling
      direct and indirect pathways.
AB  - This study examined links between parents' and children's expressed affect during
      parent-child play and children's social functioning with peers. A total of 116
      kindergarten-age children and their parents (114 mothers, 102 fathers) were
      observed during physical play interactions and were coded on global measures of
      expressed positive and negative affect. Kindergarten and 1st-grade teachers and
      peers provided measures of social competence. Latent variable path analysis with
      partial least squares was used to examine models that included "direct" and
      "indirect" pathways. Relations between parental positive affect and children's
      social competence were mediated by children's expressed positive affect. Parental
      negative affect was associated with negative social outcomes in children;
      however, these relations were not mediated by children's negative expressions.
      The strongest support for the hypothesized models was found in same-sex dyads.

PMID- 10082026
TI  - Deception by young children following noncompliance.
AB  - A paradigm devised by M. Lewis, C. Stanger, and M. W. Sullivan (1989) was adapted
      to study deception and false-belief understanding. In Study 1, 3- and 5-year-olds
      were asked not to touch a toy in the experimenter's absence. Just over half of
      the children touched the toy, and of those children, the majority denied having
      done so. Of control children who were given permission to touch the toy, all
      touched it and admitted having done so. In Study 2, 3- and 5-year-olds were asked
      not to look in a box to identify its contents. Almost all children looked, most
      denied having looked, and a minority consistently feigned ignorance of the
      contents. False-belief understanding was linked to denial of looking but not to
      feigning ignorance. Of control children who were given permission to look, all
      acknowledged looking, and they almost always revealed their knowledge of the
      contents. The studies confirm that preschoolers deceive in the context of a minor
      misdemeanor but are less effective at feigning ignorance.

PMID- 10082027
TI  - Relation of maternal responsiveness during infancy to the development of behavior
      problems in high-risk youths.
AB  - Although problematic parenting has been consistently associated with behavior
      problems in youths, prospective links between early parenting and childhood
      behavior problems are less well established. This study examined the association
      of maternal responsiveness (MRes) during infancy and behavior problems in middle
      childhood (N = 77). MRes was significantly associated with disruptive behavior
      problems but was unrelated to attention problems. Absence of MRes during infancy
      increased the risk of disruptive behavior problems in middle childhood, even with
      concurrent parenting and established risk factors for disruptive behavior
      controlled. MRes also interacted with concurrent family risk to predict
      disruptive behavior symptoms. These findings underscore the importance of early
      parenting for developmental pathways to disruptive behavior disorders in high
      risk youths. The identification of a relatively modifiable early risk factor for
      disruptive behavior problems has important implications for prevention.

PMID- 10082028
TI  - Maternal behaviors and cognitions during discipline episodes: a comparison of
      power bouts and single acts of noncompliance.
AB  - Maternal behaviors and cognitions within power bouts and single acts of
      noncompliance were compared by using 2 methodologies. Ninety mothers completed
      daily telephone interviews concerning their children's misbehavior for 12 days.
      Half of the mothers also completed a computerized simulation of 3 different power
      bouts, and the other half of the mothers completed a similar simulation of 3 sets
      of single noncompliance episodes. Mothers made behavioral intention choices and
      rated their perceptions of the child's behavior in the computer simulation.
      Results indicate that power bouts formed a special class of discipline episodes
      distinct from single noncompliance. Mothers reported more negative perceptions of
      the child as well as more aversion during extended power bouts. Discussion
      focuses on possible different types of power bouts and the need for theories of
      socialization to include the transactive nature of discipline episodes.

PMID- 10082029
TI  - The structure of genetic influences on general cognitive, language, phonological,
      and reading abilities.
AB  - The etiology of individual differences in literacy, phonological awareness, and
      language ability is reported in 126 pairs of monozygotic and dizygotic twins. At
      age 6 and 7 years, more than 60% of the variance in literacy was heritable.
      Heritabilities for 6- and 7-year-olds were .52 and .62, respectively, for
      phonological awareness and .43 and .50, respectively, for language ability. After
      genetic effects on IQ were controlled, a separate genetic influence was
      identified that acted on literacy, phonological awareness, and language. No
      genetic link between phonological awareness and literacy independent of general
      language ability was found; such covariance was mediated through environmental
      influences. Individual differences in literacy ability are substantially
      influenced by genetic factors, some of which also act on phonological awareness
      and general language ability.

PMID- 10082030
TI  - The next revolution in general surgery: radioguided surgery.

PMID- 10082031
TI  - Retrospective reviews can be learning experiences.

PMID- 10082032
TI  - Blood vessel invasion in colorectal cancer--an alternative to TNM staging?

PMID- 10082033
TI  - New success with management of recurrent rectal cancer--a reason to follow
      patients.

PMID- 10082034
TI  - Hope for a cure through earlier detection of hepatocellular cancer.

PMID- 10082035
TI  - The choice of estrogen replacement therapy after a diagnosis of breast cancer.

PMID- 10082036
TI  - Advanced breast biopsy instrumentation: not ready for prime time.

PMID- 10082037
TI  - Lymph node biopsy does not impair survival after therapeutic dissection for
      palpable melanoma metastases.
AB  - BACKGROUND: To determine the effects of disrupting a nodal basin in patients with
      American Joint Committee on Cancer stage III melanoma with clinically palpable
      lymph nodes, we studied patients who underwent therapeutic lymph node dissection
      after excisional lymph node biopsy, after fine-needle aspiration (FNA) biopsy, or
      without a preoperative biopsy. METHODS: We performed a retrospective review of
      our patients with American Joint Committee on Cancer stage III melanoma who were
      treated between January 1972 and June 1995, using data acquired from our 8200
      patient database. The study group included 670 patients with melanoma, with known
      primary tumors, who underwent therapeutic lymph node dissection for palpable
      nodal metastases diagnosed by open biopsy (227 patients), by FNA (66 patients),
      or by clinical observation without biopsy (377 patients). Regional node
      recurrence, 5-year disease-free survival, and overall survival rates were
      calculated. RESULTS: The same-basin regional node recurrence rates were similar
      for the three groups (open biopsy, 4.6%; FNA, 3.2%; no biopsy, 4.6%; P = .14).
      The 5-year disease-free survival rates were 36.8% for the open-biopsy group,
      29.6% for the FNA group, and 28.9% for the no-biopsy group (P = .08);
      corresponding 5-year overall survival rates were 40.6%, 43.9%, and 36.1%,
      respectively (P = .18). Multivariate analysis failed to identify preoperative
      biopsy as a significant risk factor. Matched-pair analysis using age, gender,
      primary tumor site, Breslow thickness, and tumor burden showed no differences in
      the 5-year disease-free survival rates (33% for the open-biopsy group vs. 27% for
      the FNA and no-biopsy groups, P = .42) and the 5-year overall survival rates (41%
      vs. 35%, P = .32). CONCLUSIONS: For patients with melanoma with palpable regional
      adenopathy, histological confirmation of clinical suspicion with either FNA or
      excisional lymph node biopsy does not adversely affect survival or recurrence
      rates.

PMID- 10082038
TI  - The progression of melanoma nodal metastasis is dependent on tumor thickness of
      the primary lesion.
AB  - BACKGROUND: Recent results of several clinical trials using the technique of
      intraoperative lymphatic mapping and sentinel lymph node (SLN) biopsy confirm the
      validity of the concept of there being an order to the progression of melanoma
      nodal metastases. This report reviews the H. Lee Moffitt Cancer Center experience
      with this procedure, one of the largest series described to date. These data
      demonstrate that the involvement of the SLNs, as well as higher-echelon nodes, is
      directly proportional to the melanoma tumor thickness, as measured by the method
      of Breslow. METHODS: The investigators at the H. Lee Moffitt Cancer Center
      retrospectively reviewed their experience using lymphatic mapping and SLN
      biopsies in the treatment of malignant melanoma. All eligible patients with
      primary malignant melanomas underwent preoperative and intraoperative mapping of
      the lymphatic drainage of their primary sites, along with SLN biopsies. All
      patients with positive SLNs underwent complete regional basin nodal dissection.
      For 20 consecutive patients with one positive SLN, all of the nodes from the
      complete lymphadenectomy were serially sectioned and examined by S-100
      immunohistochemical analysis, to detect additional metastatic disease. RESULTS:
      Six hundred ninety-three patients consented to undergo lymphatic mapping and SLN
      biopsy. The SLNs were successfully identified and collected for 688 patients,
      yielding a 99% success rate. One hundred patients (14.52%) showed evidence of
      nodal metastasis. The rates of SLN involvement for primary tumors with
      thicknesses of <0.76 mm, 0.76-1.0 mm, 1.0-1.5 mm, 1.5-4.0 mm, and >4.0 mm were
      0%, 5.3%, 8%, 19%, and 29%, respectively. Eighty-one patients underwent complete
      lymph node dissection after observation of a positive SLN, and only six patients
      with positive SLNs demonstrated metastatic disease beyond the SLN (7.4%). The
      tumor thicknesses for these six patients ranged from 2.8 to 6.0 mm. No patient
      with a tumor thickness of <2.8 mm was found to have evidence of metastatic
      disease beyond the SLN in complete lymph node dissection. All 20 patients with a
      positive SLN for whom all of the regional nodes were serially sectioned and
      examined by S-100 immunohistochemical analysis failed to show additional positive
      nodes. CONCLUSIONS: These results suggest that regional lymph node involvement
      may be dependent on the thickness of the primary tumor. As the primary tumor
      thickness increases, so does the likelihood of involvement of SLNs and higher
      regional nodes in the basin beyond the positive SLNs.

PMID- 10082039
TI  - Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous
      melanoma.
AB  - BACKGROUND: Routine elective superficial parotidectomy for patients with primary
      cutaneous melanomas of the scalp, auricle, or face has been questioned. We
      evaluated an alternative, i.e., lymphatic mapping and sentinel lymphadenectomy,
      for patients with primary cutaneous melanomas draining to the region of the
      parotid gland. PATIENTS: Retrospective review of our large (>8000 patients)
      melanoma database identified 39 patients with primary melanomas (American Joint
      Committee on Cancer stage I or II) of the scalp (n = 19), auricle (n = 11), or
      face (n = 9) who underwent intraoperative lymphatic mapping to identify a
      sentinel node (SN) in the region of the parotid gland, between June 1985 and July
      1997. RESULTS: A SN was identified in the parotid region of 37 patients (94.9%),
      four of whom had SN metastases. The mean number of SN obtained was 2.3/patient
      (range, 1-4/patient). The two patients (5.1%) for whom a parotid-region SN could
      not be identified underwent superficial parotidectomy during the same operation.
      Among the 33 patients with tumor-free SN, with a median follow-up period of 33.2
      months (range, 1-121 months), there was one (3.1%) intraparotid recurrence; thus,
      the false-negative rate was 3.1%. The procedure-related surgical morbidity rate
      was only 2.6% (one case of temporary facial nerve paresis). CONCLUSIONS: For
      patients with primary melanomas of the scalp, auricle, or face, sentinel
      lymphadenectomy can be performed accurately in the parotid region and offers a
      low-morbidity alternative to routine elective superficial parotidectomy.

PMID- 10082040
TI  - Management of symptomatic malignant melanoma of the gastrointestinal tract.
AB  - BACKGROUND: Melanoma metastatic to the gastrointestinal (GI) tract is
      asymptomatic or presents with pain, bleeding, or obstruction. To determine
      whether surgery influences outcomes, we reviewed our experience with this patient
      population. METHODS: Medical records of patients with metastatic melanoma to the
      GI tract were reviewed. Patients were divided into four groups, i.e., complete
      resection, partial debulking, unresectable, or unexplored. Analysis was performed
      using the Kaplan-Meier method. RESULTS: Fifty patients with melanoma metastatic
      to the GI tract were identified (40 men and 10 women; mean age, 44 years).
      Presenting symptoms included pain (62%), bleeding (28%), and obstruction (18%).
      Diagnosis was confirmed using contrast studies (38%), endoscopy (20%), or
      computed tomography (30%). Thirty-six patients (61%) underwent a total of 39
      operations. Seventeen patients underwent complete resection, whereas 14 underwent
      partial debulking. Five patients had unresectable lesions, and 14 patients did
      not undergo exploration because of medical contraindications. The operative
      mortality rate was 2.5% (1 of 39). The mean survival times for the unexplored and
      unresected groups were similar (4.1 months). Patients who underwent partial
      resection exhibited a longer mean survival time (8.9 months) than did patients in
      the unresected group (P < .001). The complete-resection group demonstrated a mean
      survival time of 23.5 months, which was significantly longer than that for
      patients who underwent less than complete resection (P < .0001). CONCLUSIONS:
      Metastatic melanoma to the GI tract can result in significant morbidity and
      death. Surgical resection can be performed safely. Patients for whom all sites of
      disease are completely resected experience significant improvements in survival
      times, compared with patients who undergo less than complete resection. For
      selected patients, surgical treatment of metastatic melanoma involving the GI
      tract is appropriate therapy.

PMID- 10082041
TI  - New approach to the substaging of node-positive colorectal adenocarcinoma.
AB  - BACKGROUND: Future developments in adjuvant modalities may require substaging of
      node-positive colorectal adenocarcinoma that is accurately indicative of
      individual prognoses, upon which therapeutic decisions (e.g., choice of agents
      and intensity of treatment) may be based. This study compares substaging of node
      positive colorectal cancer by venous invasion with substaging by three currently
      used methods, with respect to the ability of each method to define patient
      subsets that differ significantly in both disease-free and cancer-related
      survival rates. METHODS: A total of 171 patients with node-positive colorectal
      cancer, who had undergone potentially curative resection at least 5 years
      earlier, were retrospectively substaged by the tumor, node, metastasis (TNM)
      N1/N2, Astler-Coller C1/C2, Gastrointestinal Tumor Study Group (GITSG) C1/C2, and
      venous invasion (positive/negative) methods. Disease-free and cancer-related
      survival curves were calculated (by the Kaplan-Meier method) and compared for
      statistical significance (using the log-rank test). RESULTS: The separation of
      disease-free and cancer-related survival curves using the four methods of
      substaging node-positive colorectal cancer was as follows: TNM, P = .16 (not
      significant) and P = .12 (not significant); Astler-Coller, P < .01 and P = .006;
      GITSG, P = .067 (not significant) and P = .03; venous invasion, P = .016 and P =
      .007, respectively. CONCLUSIONS: Numerical substaging of node-positive colorectal
      cancer (TNM and GITSG methods) is an inferior predictor of prognosis, compared
      with substaging by the T value (Astler-Coller) or venous invasion methods. We
      think that the latter method is the method of choice, because it separates
      patients who have only lymphatic metastasis from patients who display microscopic
      hematogenous spread as well. This separation obviously has biological/oncological
      significance, and it may have practical therapeutic implications in the future.

PMID- 10082042
TI  - Phase II study of limited surgery for early gastric cancer: segmental gastric
      resection.
AB  - BACKGROUND: Endoscopic resection for treatment of early gastric cancer (EGC) is
      widely performed. Recently, however, surgeons began performing a limited
      operation for EGC when endoscopic resection was not indicated. This report
      discusses the surgical technique and the results of the limited operation, which
      is generally referred to as "segmental resection" (SR). METHODS: Since 1990, a
      total of 50 patients with intramucosal invasive EGC of the middle stomach
      underwent SR. The procedure included a limited gastrectomy, limited lymph node
      dissection, and preservation of the vagal nerve. We examined the surgical risk,
      postoperative complications, and patient survival rates and compared the results
      for the SR-treated patients (group A) with results for patients with EGC who
      underwent subtotal gastrectomy and systemic lymph node dissection (group B).
      RESULTS: Blood loss was less in group A (239 +/- 180 ml) than in group B (342 +/-
      176 ml) (P < .05). The incidence of postoperative complications was also lower in
      group A (2.0%) than in group B (14.0%) (P < .05). The incidence of postoperative
      cholelithiasis was lower in group A (4.0%) than in group B (18.0%) (P < .05). All
      patients in both groups are alive without recurrence. CONCLUSIONS: Compared with
      distal gastrectomy, SR for EGC of the middle stomach decreased the surgical risk
      and postoperative complications without increasing the recurrence rate.

PMID- 10082043
TI  - Surgical salvage of recurrent rectal carcinoma after curative resection: a 10
      year experience.
AB  - BACKGROUND: Local recurrence after resection of rectal carcinoma is a difficult
      clinical problem that adversely affects both survival and quality of life.
      Surgical resection is possible for a subset of patients with localized
      recurrences. We reviewed our experience with surgical salvage of recurrent rectal
      carcinoma, to determine predictors of resectability and postsalvage survival
      rates. METHODS: A 10-year, retrospective analysis of 131 patients who underwent
      exploration with curative intent for local recurrence after radical resection of
      rectal carcinomas, in a single referral institution, was performed. Preoperative
      and pathological factors were examined for their ability to predict postresection
      survival rates and resectability. RESULTS: The overall 5-year survival rate for
      patients who underwent exploration with curative intent was 24%. Resection of
      recurrent disease was possible for 103 of 131 (79%) patients, with a resulting 5
      year survival rate of 31%. Patients who were treated initially with abdomino
      perineal resection (n = 35) presented later and were less likely to have
      resectable tumors than were those treated initially with some form of sphincter
      preserving resection (n = 96). Among patients who could undergo resection, normal
      carcinoembryonic antigen levels and recurrent disease limited to the bowel wall
      were both favorable features. CONCLUSIONS: Surgical salvage of local recurrence
      after radical resection of rectal carcinoma can be performed safely and can
      result in substantial long-term survival benefits for selected patients.

PMID- 10082044
TI  - Soluble interleukin-2 receptor levels in hepatocellular cancer: a more sensitive
      marker than alfa fetoprotein.
AB  - BACKGROUND: Worldwide, the majority of cases of hepatocellular cancer (HCC) arise
      in individuals with chronic hepatitis B or C virus infections. Early detection of
      HCC in these patients provides the best chance for curative treatment, but serum
      alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs.
      The purpose of this study was to determine: (1) whether soluble interleukin-2
      receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC
      patients and (2) whether sIL-2R levels are useful as a marker of successful
      treatment and recurrence of disease. PATIENTS AND METHODS: We are performing a
      prospective screening program with high-risk, chronic hepatitis virus-infected
      patients to detect HCC. Patients are screened by using abdominal ultrasonography,
      serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels
      were established using results from 174 healthy volunteers with no evidence of
      hepatitis virus infection or HCC. RESULTS: HCC has been diagnosed in 99 patients
      from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79
      patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients
      (99%, P < .01, chi2 test). For 27 of the 99 patients (27%), HCC was diagnosed at
      an early stage and complete resection or ablation was performed. Serum sIL-2R
      levels returned to normal in all 27 patients after treatment, whereas AFP levels
      remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this
      group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16,
      whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P <
      .05). CONCLUSIONS: This study with chronic hepatitis B or C virus-infected
      patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC
      with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R
      levels are a more sensitive marker of successful treatment and recurrence of HCC.
      Based on these findings, we now use serum sIL-2R measurements both to screen high
      risk patients and to monitor treatment responses in patients with hepatitis who
      develop HCC.

PMID- 10082045
TI  - Interleukin-12 gene transfer results in CD8-dependent regression of murine CT26
      liver tumors.
AB  - BACKGROUND: Interleukin (IL)-12 has potent antitumor effects in animal models. We
      hypothesized that direct transfer of the IL-12 gene to established tumors would
      result in tumor regression without significant toxicity. METHODS: Liver tumors
      were established by direct injection of CT26, a murine adenocarcinoma, into the
      livers of BALB/c mice, followed by three transfections with either murine IL-12,
      murine granulocyte-macrophage colony-stimulating factor, or luciferase cDNA using
      particle-mediated gene transfer. To assess the mechanism of this effect,
      immunohistochemical staining and depletion experiments with anti-CD4 or -CD8
      antibodies were performed. RESULTS: Progressive growth of primary tumors and
      carcinomatosis were present by day 16 after transfection with luciferase or
      murine granulocyte-macrophage colony-stimulating factor. At 50 days, complete
      regression of tumor was evident in seven of eight IL-12-treated mice (P < .001).
      In IL-12-transfected livers, immunohistochemical staining revealed an increase in
      CD8+ T cells. Selective depletion of CD4+ or CD8+ T cells was performed before
      and during transfection with murine IL-12. At 50 days, 75% of control mice were
      tumor-free. Only 46% of CD4+ cell-depleted mice (P = .143) and 7% of CD8+ cell
      depleted mice (P < .001) were tumor-free. CONCLUSIONS: IL-12 gene transfer using
      particle-mediated gene transfer results in complete regression of established
      CT26 liver tumors in 88% of mice; this effect is dependent on CD8+ T cells.

PMID- 10082046
TI  - One hundred consecutive advanced breast biopsy instrumentation procedures:
      complications, costs, and outcome.
AB  - BACKGROUND: Needle localization and excision have been the preferred techniques
      for treating nonpalpable mammographic abnormalities. Recently, a less invasive
      approach, using the Advanced Breast Biopsy Instrumentation (ABBI) system, was
      introduced. This study was undertaken to determine the feasibility, utility, and
      cost of this new alternative approach. METHODS: Between April 1996 and May 1997,
      100 consecutive women underwent excisional breast biopsies using the ABBI system.
      Demographic information, mammographic findings, pathological findings,
      hospital/professional fees, complications, and subsequent interventions were
      documented. RESULTS: Excisional biopsies using the ABBI system were successful
      for 99 women (average age, 62 years; range, 34-87 years). Of the 99 lesions
      removed with the ABBI system, 27 were microcalcifications, 60 were suspicious
      solid nodules, and 12 were nodules with microcalcifications. The ABBI system was
      used in an outpatient surgical setting, with only one patient requiring sedation
      (because of anxiety). Cancer was seen in the biopsy specimens for 18 patients,
      seven of whom (35%) exhibited no residual tumor at the time of definitive
      treatment. Postoperative hematomas occurred in two patients; one hematoma
      required surgical drainage. One missed cancer was detected in follow-up
      mammograms 6 months after biopsy. The total average procedural cost was $3406.44
      +/- 486.63. CONCLUSIONS: Excisional breast biopsy using the ABBI system is an
      effective diagnostic method. It has a low complication rate, and its cost is
      comparable to that of classical needle localization.

PMID- 10082047
TI  - Estrogen replacement therapy and breast cancer: analysis of age of onset and
      tumor characteristics.
AB  - BACKGROUND: The use of exogenous estrogen has been scrutinized as a risk factor
      for breast cancer formation. This prospective study addresses the relationship
      between the use of estrogen replacement therapy and the age of onset of breast
      cancer. In addition, an analysis of differences in pathological features of
      breast cancer between estrogen users and non-estrogen-users was evaluated.
      METHODS: A total of 425 women (age, > or = 50 years) were evaluated during a 4
      year period (1994-1997). Data, including the age at diagnosis, method of
      detection, family history, use of estrogen therapy, and tumor ploidy, S-phase
      fraction, histological category, estrogen receptor positivity, and grade, were
      prospectively collected. Data from a control group of 657 women without a
      diagnosis of breast cancer were obtained from the Evanston Northwestern division
      of the Women's Health Initiative. Significant associations between the use of
      estrogen and pathological parameters were determined using the chi2 test and t
      test (P < .05). RESULTS: At the time of breast cancer diagnosis, 140 patients
      were currently receiving estrogen and 202 patients had no history of estrogen
      use. Eighty-three patients were excluded from analysis (76 patients had a history
      of previous but not current use of estrogen therapy, four women used only
      progesterone, and three patients provided incomplete information). There was no
      difference between patients with breast cancer using estrogen at the time of
      diagnosis and those with no history of estrogen use with respect to tumor size,
      age of menopause, family history, mammographic sensitivity, axillary lymph node
      status, and histological features. Women using estrogen at the time of diagnosis
      were younger at the time of breast cancer diagnosis, by an average of 5.1 years
      (61.3 years vs. 66.4 years, P < .001). Women without a history of breast cancer
      who were receiving estrogen therapy were an average of 2.4 years younger (63.3
      years vs. 65.7 years, P < .001) than women without a history of breast cancer who
      were not receiving estrogen therapy. Patients with breast cancer receiving
      estrogen also tended to have more grade II tumors (45.9% vs. 36.5%, P = .045) and
      fewer grade III tumors (25.6% vs. 37.0%, P = .015), compared with women not
      receiving estrogen therapy at the time of their diagnoses. Estrogen receptor
      positivity was noted to be more frequent for estrogen users presenting with
      lobular carcinoma (85% vs. 76%, P = .042) and less frequent for estrogen users
      presenting with ductal carcinoma (72% vs. 85%, P = .003). CONCLUSIONS: A
      significantly earlier age of diagnosis for women receiving estrogen therapy
      suggests that exogenous estrogen may accelerate the pathogenesis of
      postmenopausal breast cancer. Estrogen therapy may also play a role in altering
      the grade and estrogen receptor positivity for certain histological types of
      breast cancer.

PMID- 10082048
TI  - Hormone replacement therapy and breast cancer.
AB  - The use of hormone replacement therapy by postmenopausal women with a history of
      breast cancer is a subject of considerable controversy. There are no scientific
      studies that have appropriately examined the issue, and current practice is often
      based on inferences from indirect evidence, anecdotal experience, and personal
      bias. Our understanding of the effects of exogenous, as well as endogenous,
      hormones on normal and neoplastic breast tissue provides some insights but is not
      an appropriate basis for clinical practice. The effects of exogenous hormone
      replacement on the overall health of postmenopausal women, including psychosocial
      issues, cardiovascular risks, and the morbidity of osteoporosis, must be
      understood before patients can be counseled appropriately. Treatment of patients
      must be individualized. The rapidly expanding area of nonhormonal therapies for
      the treatment of postmenopausal health risks and the treatment of symptomatic
      complaints in postmenopausal women has already led to a reevaluation of the use
      of exogenous hormones among all women. A prospective randomized trial that
      examines the effects of hormone replacement on women with a history of breast
      cancer is currently underway and will provide valuable data to address these
      issues. The aim of this review is to outline the scientific basis for the
      association between estrogen and breast cancer and to provide a framework in
      which individualized recommendations concerning the use of hormone replacement
      therapy can be made for patients with breast cancer.

PMID- 10082049
TI  - Cellular and biological therapies of gastrointestinal tumors: overview of
      clinical trials.
AB  - Because of the high relapse rate of resected gastrointestinal malignancies and
      the modest responses of metastatic disease to currently available therapies,
      biologic agents that harness host-tumor immunologic interactions have received
      increased attention. Based on promising preclinical data, current clinical trials
      in cellular and biologic therapies are evaluating the safety and efficacy of
      passive immunotherapy with tumor-reactive lymphocytes activated ex vivo and
      active immunotherapy with peptide, viral vector, and cellular vaccines. This
      review will describe the background, rationale, and experimental approach of
      these clinical trials. Although equally promising, antibodies, gene therapies,
      and antiangiogenic strategies will not be discussed.

PMID- 10082050
TI  - WWW review.

PMID- 10082051
TI  - Clinical course of accommodative esotropia.

PMID- 10082052
TI  - Explaining presbyopia to patients.

PMID- 10082053
TI  - Improvement of visual function in an adult amblyope.
AB  - PURPOSE: In this case report, the efficacy of occlusion therapy was investigated
      in a strabismic amblyope above the currently accepted age for treatment. Success
      was assessed not simply by a change in visual acuity, but by examining a number
      of parameters which relate to both sensory and motor aspects of visual function.
      METHODS: As well as routine orthoptic and optometric evaluation, additional tests
      were administered as follows: high and low contrast LogMAR Crowded Acuity, repeat
      letter acuity, and hyperacuity measurements. RESULTS: A functional loss in each
      of the tests used was demonstrated, and occlusion therapy appeared to improve all
      aspects of the amblyopia, with a significant difference in pre- and post-therapy
      results. CONCLUSIONS: The results of this study suggest that: (1) occlusion
      therapy can produce substantial improvements in visual function in adult
      amblyopia; (2) many aspects of visual function can improve beyond the traditional
      critical periods for development in amblyopia; and (3) with good patient
      compliance and cooperation, age should not be the critical factor in the
      initiation of treatment for amblyopia.

PMID- 10082054
TI  - Prevalence of chief complaints in a pediatric clinic population.
AB  - PURPOSE: To determine the type and frequency of chief complaints reported by
      parents of pediatric patients younger than 8 years of age in an optometry clinic.
      There have been many reports on prevalence of pediatric eye and vision disorders;
      however, the frequency of presenting complaints has not been carefully
      investigated. METHODS: 578 patient charts were retrospectively evaluated to
      determine the entering chief complaint, representing a 28-month time period
      between January 1993 and April 1995. The subjects were classified by age, and the
      chief complaint was placed in one of eight categories. RESULTS: The most
      frequently reported (30.1%) entering complaint for all subjects was the need for
      a routine vision examination. Each age category, however, had a unique
      distribution of complaints. Infants (1 to 11 months of age, n = 24) and young
      school age children (6 to 7-11 years of age, N = 233) most frequently reported
      complaints in the "other" category, at rates of 37.5% and 38.2%, respectively.
      Toddlers (12 to 36 months of age, N = 61) most commonly presented with complaints
      of an observed eye turn (39.3%), and preschoolers (3 to 5-11 years of age, N =
      260) presented mainly for routine vision examinations (48.9%). CONCLUSIONS: There
      was a large percentage of patients presenting for routine vision care, which may
      represent an encouraging trend in public education efforts concerning children's
      vision care needs. The relative frequency of chief complaints in each age
      category prepares the eye care practitioner to address common parental concerns.
      This information can help to improve vision care education and services for the
      pediatric population.

PMID- 10082055
TI  - The clinical efficacy of paremyd with and without dapiprazole in subjects with
      light and dark brown irides.
AB  - BACKGROUND: Paremyd, a mydriatic formulation of 0.25% tropicamide and 1.0%
      hydroxyamphetamine hydrobromide provides adequate dilation for binocular indirect
      ophthalmoscopy in young Caucasians. We studied the clinical effectiveness of
      Paremyd in dilating heavily pigmented eyes by comparing its mydriatic efficacy in
      Blacks, Asians and Caucasians with light and dark brown irides. We also evaluated
      the efficacy of one drop of dapiprazole (Rev-Eyes) in reversing Paremyd-induced
      mydriasis in our subject sample. METHODS: In a masked, randomized, controlled
      experimental design, several visual functions which included pupillary dilation,
      near visual acuity, amplitude of accommodation, ocular hyperemia, and discomfort
      glare were measured at 30-min intervals, for a total of 300 min, in subjects
      dilated with a single drop of Paremyd in each eye. Ease of binocular indirect
      ophthalmoscopy was also assessed. A 3-way analysis of variance was used to assess
      changes in these measures as function of irides color/pigmentation (designated as
      light or dark brown iris color), presence or absence of dapiprazole, and test
      time interval. RESULTS: We found that subjects in our light brown irides group
      (mainly Caucasians) dilated faster than subjects in our dark brown irides group
      (mainly Blacks). Dapiprazole increased the speed of recovery from pupillary
      dilation for all subjects, but more so for those with light rather than dark
      brown irides. Similarly, subjects with light rather than dark brown irides
      recovered accommodative function more quickly. Although neither the use of
      dapiprazole nor the degree of iris color/pigmentation was significantly related
      to visual acuity or glare discomfort, there was a clear trend that these visual
      measures were affected to a greater degree in subjects with dark brown (primarily
      Blacks) rather than light brown irides. Overall, Paremyd provided adequate
      dilation for binocular indirect ophthalmoscopy in all subjects irrespective of
      iris color/pigmentation. CONCLUSIONS: Our data indicate that a single drop of
      Paremyd provides adequate mydriasis, without significant side effects, for
      routine fundus examination of all subjects, independent of iris
      color/pigmentation. Furthermore, a single drop of dapiprazole was effective in
      speeding the return of pupillary dilation in most subjects, but had no
      significant effect on accommodation, near visual acuity or glare discomfort. Side
      effects such as stinging upon instillation, conjunctival hyperemia, and a few
      instances of ptosis, with possible additional cost to patients, appear to lessen
      its overall clinical benefit.

PMID- 10082056
TI  - Cycloplegia in African-American children.
AB  - PURPOSE: The selection of a cycloplegic agent depends on the desired outcome, the
      characteristics of the patient receiving the drug, and the associated risks. The
      Orinda Longitudinal Study of Myopia (OLSM) has used 1% tropicamide to assess the
      ocular components and cycloplegic refractions in a large cohort of predominantly
      Caucasian children. Although tropicamide has provided adequate cycloplegia and
      mydriasis for the OLSM cohort, conventional clinical wisdom and scientific
      investigations have suggested that tropicamide might not produce adequate
      cycloplegia and mydriasis for subjects with darker iris pigmentation. In this
      study one drop of 1% tropicamide followed by one drop of 1% cyclopentolate was
      used to determine their effectiveness in producing adequate cycloplegia and
      mydriasis for cycloplegic refraction and ocular component measurements in a group
      of African-American children. METHODS: Nineteen children [age range 5.5 to 15.6
      years, mean 8.4 years +/- (SD) 2.5 years] were tested at Family HealthCare of
      Alabama, Eutaw, AL. Their accommodative responses were measured using a Canon R-1
      autorefractor prior to and at 30, 45, and 60 min after instillation of one drop
      of 0.5% proparacaine, 1% tropicamide (Mydriacyl), and 1% cyclopentolate
      (Cyclogyl) in both eyes. A target of 20/155 letters in a 4x4 grid positioned
      behind a +6.50 diopter (D) Badal lens provided accommodative stimuli of 1.00 D,
      2.00 D, and 4.00 D. RESULTS: All results are presented as mean +/-1 SD. Pupils,
      measured from video frames, dilated rapidly and maximally at 30 min after
      instillation of eye drops (7.3+/-0.5 mm) Predilation, the mean accommodative
      responses were 0.17+/-0.29 D for the 1.00 D stimulus, 1.01+/-0.40 D for the 2.00
      D stimulus, and 2.77+/-0.74 for the 4.00 D stimulus. At 30 min after drop
      instillation, the responses were 0.07+/-0.14 D for the 1.00 D stimulus, 0.36+/
      0.35 D for the 2.00 D stimulus, and 0.77+/-0.61 for the 4.00 D stimulus. Results
      were very similar at 45 and 60 min after drop instillation. CONCLUSIONS:
      Combining 1% tropicamide and 1% cyclopentolate was very effective in providing
      both cycloplegia and mydriasis adequate for ocular biometry and cycloplegic
      refractions 30 min after drop instillation in African-American children.

PMID- 10082057
TI  - Accuracy of the tomey topographic modeling system in measuring surface elevations
      of asymmetric objects.
AB  - BACKGROUND: Most studies have assessed the accuracy of videokeratographic systems
      using spheres, ellipsoids, or toric surfaces. Most human corneas are asymmetric
      to some degree and many pathological corneas are markedly asymmetric. To date,
      little work has been done to ascertain the accuracy of videokeratographic systems
      for measuring the shape of asymmetric objects. PURPOSE: The purpose of this study
      is to determine the accuracy with which the Tomey Topographic Modeling System can
      evaluate the topography of asymmetric surfaces. METHODS: Calibrated ellipsoidal
      test objects were tilted with respect to the videokeratometric axis to create
      asymmetric test surfaces with known characteristics. RESULTS: Root mean squared
      error of all the measured surface elevations varied from 0.7 microm to 11.3
      microm. Although there was a trend for greater error with the more asymmetric
      surfaces, the trend was not statistically significant. Accuracy was not dependent
      on apical radius. Measurement error increased toward the periphery. CONCLUSIONS:
      For the Tomey Topographic Modeling System, the accuracy in measurement of smooth,
      asymmetric surfaces is comparable the accuracy in measurement of symmetric
      surfaces.

PMID- 10082058
TI  - Comparison of letter and Vernier acuities with dioptric and diffusive blur.
AB  - We assessed the influence of dioptric and diffusive blur on normal subjects'
      letter and Vernier acuity in two experiments. In the first experiment, letter
      acuity was measured for isolated black Sloan letters and Vernier acuity was
      determined for a pair of black vertical abutting or nonabutting lines. Targets
      were viewed through plus lenses that produced 0, 1, 2, 4, and 8 D of dioptric
      blur. In the second experiment, letter acuity was determined for bright 4
      position Ts and Vernier acuity was measured for a pair of bright abutting
      vertical lines. Six levels of imposed diffusive blur were produced by varying the
      distance between a ground glass screen and the oscilloscope on which the targets
      were presented. The results of both experiments indicate that letter and Vernier
      acuity for abutting or closely separated lines worsen in parallel curvilinear
      fashion, as long as the lines comprising the Vernier targets remain equally
      detectable when various amounts of dioptric and diffusive blur are imposed. We
      conclude that both dioptric and diffusive blur introduce common processing
      limitations for letter and Vernier acuity.

PMID- 10082059
TI  - Fundus magnification produced during direct ophthalmoscopy of the corrected eye.
AB  - The clinical significance of fundus magnification produced during direct
      ophthalmoscopy of the corrected eye has not been fully established. Based on
      paraxial ray tracing, fundus magnification (M) can be defined by a simple
      equation, M = (K'/4) x (Fs/K), where K' is the dioptric axial power of the eye,
      Fs is the correcting thin lens power and K is the ocular ametropia. Refractive
      myopes produce greater fundus magnification than axial myopes, whereas refractive
      hyperopes produce lower fundus magnification than axial hyperopes. If we assume
      15 x fundus magnification as our standard magnification for an emmetropic reduced
      eye, then wearing glasses or putting the focusing lens at or close to the
      anterior focus of the eye is able to achieve the standard magnification for axial
      myope and axial hyperope, whereas wearing contact lenses is able to achieve the
      standard magnification for refractive myope and refractive hyperope. Vertex
      distance has greater influence on fundus magnification produced during direct
      ophthalmoscopy than other funduscopic techniques. In conclusion, the newly
      defined formula has clinical applications during direct ophthalmoscopy.

PMID- 10082060
TI  - Adolescent use of illicit drugs other than marijuana: how important is social
      bonding and for which ethnic groups?
AB  - We predicted Grade 12 use of illicit drugs other than marijuana ("hard" drugs)
      from characteristics at Grade 10, examining the protective value of social bonds
      and testing whether certain social bonds have greater importance for some
      racial/ethnic groups. We also explored the association of previous substance use
      with later "hard" drug use when social bonds and a broad range of other personal
      and environmental variables are statistically controlled. Bonds with family were
      inversely related to any use of illicit drugs other than marijuana; various forms
      of prior use were positively related to both any and frequent use. However,
      variables other than social bonds and prior use were equal or stronger predictors
      of both outcomes. Some differences were obtained across racial groups: African
      Americans were less likely to use illicit drugs other than marijuana, Mexican
      Americans were more affected by family factors than were other groups, and Asian
      Americans were more affected by school failure. Implications for prevention are
      discussed.

PMID- 10082061
TI  - Sleep, anxiety, and depression in abstinent and drinking alcoholics.
AB  - A group of alcoholic men were followed-up 8 years after discharge from hospital.
      The interview included items on sleep, anxiety, and depression. The sample was
      divided into abstinent and drinking subjects. Sleep data were factor analyzed.
      Only the Alcohol-Abstinence Sleep Factor significantly correlated with drinking
      status. The Alcohol-Abstinence Sleep Factor was also the primary correlate of
      anxiety and depression. Fewer abstinent subjects reported anxiety and depression.
      Sleep variables, anxiety, and depression are considered as possible markers of
      relapse in persons treated for alcoholism.

PMID- 10082062
TI  - The "concerned other" call: using family links and networks to overcome
      resistance to addiction treatment.
AB  - Untreated chemical dependency costs the United States over $165 billion annually.
      Meanwhile, treatment offsets these costs by a ratio of $7 saved for every $1
      spent. But the vast majority of chemically dependent people (CDPs) remain
      uninvolved in either treatment or self-help groups. It is therefore imperative
      that more effective ways be developed for therapeutically engaging them. One
      avenue is to maximize the opportunity presented when a "concerned other" (CO)
      person-such as a family member, friend, coworker, or clergy member-contacts a
      treatment agency to get help for a CDP. This paper provides a method for handling
      such calls. Specific guidelines are presented as to (a) the kind of information
      to b e gathered, (b) procedures to be followed, and (c) options to be offered
      toward mobilizing the CO and other family/social network members in successfully
      effecting CDP treatment engagement.

PMID- 10082063
TI  - The drinker's children.
AB  - There is no doubt that growing up in a home where one or both parents misuse
      alcohol is undesirable. However, it is far less certain that this predicament is
      responsible for psychological damage to the child in the long term. This paper
      reviews the literature on the psychological effects on children of parental
      alcohol misuse and concludes that research needs to move beyond crude comparisons
      between alcohol-affected and nonalcohol-affected homes to a search for the
      precise mechanism(s) responsible for mediating any statistical associations
      between parental drinking and psychological deficits in children.

PMID- 10082064
TI  - Gender, perceptions of harm, and other social predictors of alcohol use in a
      Punjabi community in the Toronto area.
AB  - Based on self-administered face-to-face interviews conducted in 1992-93 with 524
      members of the Punjabi community in Peel, near Toronto, this study investigates
      the factors associated with alcohol use in the community. Results from alcohol
      and other drug surveys in Ontario are used for comparison between the two samples
      regarding drinking and sociodemographic characteristics. Bivariate analyses
      indicate a lower prevalence rate of drinking among the Punjabi sample than the
      Ontario population, especially among women. In spite of this, a majority of the
      Punjabi respondents perceive that alcohol problems are widespread in their
      community. Logistic regression results show that sex, importance of religion,
      perceived risk of alcohol, and opinion on alcohol price in the province are
      significantly associated with alcohol use. The effects of socioeconomic status,
      perception of public drunkenness, and levels of integration appear to be not
      significant. In light of these results, some implications for "alcohol abuse"
      prevention strategies are discussed.

PMID- 10082065
TI  - Aggregate comparisons of self-reported versus nonself-reported drinking in a
      general population survey.
AB  - Insight is gained into the validity of self-reported drinking in the general
      population by comparing self-reports and nonself-reports on the aggregate level.
      Married and cohabiting respondents of a general population survey (N = 2,169)
      were asked about both their own and their spouses' drinking behavior. It was
      found that on the aggregate level, distribution of "moderate" drinking and usual
      frequency of drinking is similar between self- and nonself-reports. Self-reported
      "heavy" drinking, however, is lower than nonself-reported "heavy" drinking among
      women in general, older women, and women with a lower education. Among men in
      general and older men in particular, however, self-reported occasional "heavy"
      drinking was found to be higher. The similar distribution of "moderate" drinking
      and usual frequency of drinking between self- versus nonself-reports gives
      reassurance about the validity of self-reported drinking behavior. The
      discordance in self-reported versus nonself-reported "heavy" drinking, however,
      raises questions about the validity. Interpretation of the discordance is not
      conclusive: more research (experimental and qualitative) has to be done to
      disentangle this issue.

PMID- 10082066
TI  - A review of literature on drug use in Sub-Saharan Africa countries and its
      economic and social implications.
AB  - The drug problem in Africa cannot be seen as an isolated phenomenon but rather as
      part of the larger narcoscape which partakes of the fluid yet disjunctive
      qualities of Appadurai's landscapes. In this volatile environment, the
      transformation of Sub-Saharan Africa (SSA) nations from transit points in an
      international drug network to consumer countries seems inevitable. At the same
      time, Africa has undergone rapid economic and social changes that have facilitate
      this shift. A review of the literature reveals that there is a pressing need to
      investigate current trends and patterns of drug use in the countries of SSA.
      These nations, struggling with the consequences of AIDS, famine, refugees, and
      political unrest, could ill afford to address the consequences of widespread drug
      use. It is critical, therefore, that they address the drug problem before it
      reaches crisis proportions. To do so, they need information describing the
      magnitude of the problem as well as a firm understanding of the relationships
      between drug use and crime, unemployment, violence, and the breakdown of family
      life. The more that is known about the nature and complexity of drug use in
      Africa, the better policymakers can formulate a sound and effective strategy to
      curtail the drug "epidemic."

PMID- 10082067
TI  - Cigarette use by adolescents: attitude-behavior relationships.
AB  - Structural equation models were used to test the effectiveness of various
      theories in predicting cigarette smoking among adolescents. Maximum-likelihood
      estimation, as implemented in LISREL for Windows 8.12, was used to compare the
      theory of reasoned action (TRA), the theory of planned behavior, and a modified
      version of the theory of reasoned action incorporating past behavior. Respondents
      consisted of 225 high school students who were questioned in 1994 about their
      attitudes, subjective norms, perceived behavioral control, past behavior,
      intentions, and actual behavior relating to the use of cigarettes. Results
      indicated that the modification of the TRA incorporating past behavior provided a
      marginally better fit than the other models. For this group of high school
      students, attitudes toward smoking, past behavior in relation to smoking, and
      perceptions of what significant others think they should do were significant
      predictors of their intentions to smoke. Intentions, together with past behavior,
      predicted their actual behavior. The models used in the present research show
      that this behavior can be explained with reference to a small number of key
      variables which are useful for furthering our understanding of the structure of
      adolescent smoking.

PMID- 10082068
TI  - The Internet and drug safety: what are the implications for pharmacovigilance?
AB  - Use of the Internet is becoming widespread throughout the world. Its use in the
      domain of drug safety and pharmacovigilance is spreading rapidly. Governments and
      industry have taken the lead in developing extensive web sites. The US Food and
      Drug Administration (FDA), the European Agency for the Evaluation of Medicinal
      Products (EMEA) and other agencies have developed sites containing enormous
      amounts of information both on pharmacovigilance in general and on specific drugs
      in particular. Under the US 'Freedom of Information Act' the FDA has put major
      parts of its adverse event database on line. Regulatory documents are also
      available from the FDA site or from hyperlinks described in the site. The US
      Center for Drug Evaluation and Research updates its site most days and maintains
      a free automated e-mail announcement service of these updates. Similarly, the
      EMEA updates its site frequently and publishes extensive material including
      regulatory documents, guidelines, European Public Assessment Reports on newly
      approved medications and other useful information. A free update service by e
      mail is also available. Although English is the primary language used on the EMEA
      site, some of the information is available in other languages. Pharmaceutical
      companies are not using the Internet for pharmacovigilance yet. Rather, the
      Internet is being used for promotion of their products and for informing
      consumers on general information on diseases, for financial and investor data and
      for employment opportunities, etc. Other organisations such as lobbies, consumer
      groups and medical journals are also beginning to use the Internet. The
      electronic transmission of safety information, using the standards developed by
      the International Conference on Harmonization, is currently being tested for the
      transmission of individual patient adverse event information between companies
      and governments. In addition, the FDA has begun to accept adverse events from
      healthcare providers and consumers directly on line using an electronic version
      of its MedWatch form. It is expected that these developments will change the
      nature of the way pharmacovigilance is carried out. Significant issues will arise
      from this including privacy concerns. The European Union's 1995 directive on 'the
      protection of individuals with regard to the processing of personal data and on
      the free movement of such data (95/46/EC)' went into effect in October 1998. The
      enabling legislation now being passed by the member states will produce
      significant changes in the way companies and governments handle individual
      patient data in order to assure the privacy and protection of individuals.

PMID- 10082069
TI  - The medical dictionary for regulatory activities (MedDRA).
AB  - The International Conference on Harmonisation has agreed upon the structure and
      content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0
      which should become available in the early part of 1999. This medical terminology
      is intended for use in the pre- and postmarketing phases of the medicines
      regulatory process, covering diagnoses, symptoms and signs, adverse drug
      reactions and therapeutic indications, the names and qualitative results of
      investigations, surgical and medical procedures, and medical/social history. It
      can be used for recording adverse events and medical history in clinical trials,
      in the analysis and tabulations of data from these trials and in the expedited
      submission of safety data to government regulatory authorities, as well as in
      constructing standard product information and documentation for applications for
      marketing authorisation. After licensing of a medicine, it may be used in
      pharmacovigilance and is expected to be the preferred terminology for
      international electronic regulatory communication. MedDRA is a hierarchical
      terminology with 5 levels and is multiaxial: terms may exist in more than 1
      vertical axis, providing specificity of terms for data entry and flexibility in
      data retrieval. Terms in MedDRA were derived from several sources including the
      WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of
      Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD)
      9 and ICD9-CM. It will be maintained, further developed and distributed by a
      Maintenance Support Services Organisation (MSSO). It is anticipated that using
      MedDRA will improve the quality of data captured on databases, support effective
      analysis by providing clinically relevant groupings of terms and facilitate
      electronic communication of data, although as a new tool, users will need to
      invest time in gaining expertise in its use.

PMID- 10082070
TI  - A risk-benefit assessment of anti-obesity drugs.
AB  - This review evaluates the benefits and potential health risks of the currently
      used drugs that are approved for the pharmacological treatment of obesity.
      Analysis of several long term clinical trials indicates that all of these drugs
      are efficient in reducing excess bodyweight, and that the majority of them allow
      the maintenance of the reduced bodyweight for at least 1 year. However, the loss
      of bodyweight attributable to these drugs is in general rather modest,
      approaching only 0.2 kg per week during the first 6 months of treatment, and at
      least a partial regain of bodyweight occurs when these drugs are used for periods
      longer than 1 year. All of these drugs induce several adverse effects. Although
      most of these adverse effects are mild and transient, the prolonged use of
      adrenergic or serotonergic anorectic drugs, or their use as combination
      treatment, may induce serious and potentially life-threatening complications,
      such as primary pulmonary hypertension or valvular heart disease. The adrenergic
      appetite-suppressing drugs are not recommended for the treatment of obesity,
      since their safety has never been evaluated in long term clinical trials, and
      because of their stimulatory effects on the cardiovascular and nervous systems.
      The serotonergic drugs, such as fenfluramine and dexfenfluramine, have been the
      most widely used during the past decade; however, both these compounds have
      recently been withdrawn from the market, since their use was associated with
      serious cardiovascular complications. The safety of the prolonged therapeutic use
      of newer compounds such as sibutramine and orlistat has not yet been
      demonstrated. Therefore, none of the currently available anti-obesity medications
      meets the criteria of an 'ideal anti-obesity drug' and, if prescribed, these
      medications should be used with caution and only under careful medical
      supervision. Since obesity is recognised as a chronic health-threatening
      condition, and since classical behavioural therapeutic approaches lack long term
      efficacy, there is clearly a need for an efficient pharmacological treatment
      offering an acceptable safety profile. Such a treatment is not available at
      present. Development of new agents and a more careful assessment of the safety of
      currently available drugs are needed.

PMID- 10082071
TI  - Comparative tolerability and efficacy of treatments for impotence.
AB  - Modern pharmacological treatment of impotence is determined by the presenting
      symptoms. Since this involves symptomatology with a heterogenous aetiology, many
      different drugs are involved in the treatment of impotence. Drugs used for libido
      and arousal problems include testosterone, yohimbine, trazodone and apomorphine.
      Since patient self-assessment is the only parameter that can be used to measure
      the result of treatment and positive results are seldom affirmed, no positive
      benefit of these agents can be assumed at present. Oral medications for erectile
      dysfunction include yohimbine, trazodone, apomorphine, phentolamine, arginine and
      sildenafil. Of these drugs, sildenafil has been the most systematically studied
      for effectiveness, but long term safety data await the results of post-marketing
      surveillance. Of the ejaculation disorder therapies, treatments for premature
      ejaculation are the best studied. Favourable results have been obtained with
      clomipramine, paroxetine and fluoxetine. The safety of these medications has been
      assessed through their long term use in psychiatry. Intracavernous self
      injections for erectile disorders are performed using a variety of drugs and drug
      mixtures. Only alprostadil and the combination of papaverine with phentolamine
      are widely used. Alprostadil is very well tolerated; however, penile pain is a
      serious problem in a significant proportion of patients. Papaverine in
      combination with phentolamine is effective, but penile fibrosis and priapism
      occur more often than with the use of alprostadil. Several new developments in
      this area are currently under way. Alternative routes for medication for erectile
      dysfunction include ointments and patches to the penile skin and the glans. Only
      transurethral alprostadil, 'MUSE' (medicated urethral system for erection) has
      been shown to be effective in large trials. Long term safety still has to be
      demonstrated, but the 1-year safety profile is encouraging. In general, the end
      points of impotence treatment studies are very diverse so efficacy data can only
      be assessed in comparative studies. However, long term comparison studies have
      not been performed. Safety demands must be set very high for this type of
      treatment since the disorders being treated present no threat to the patient's
      health.

PMID- 10082072
TI  - Drug interactions of HIV protease inhibitors.
AB  - All the currently available protease inhibitors are metabolised by the cytochrome
      P450 (CYP) enzyme system. All are inhibitors of CYP3A4, ranging from weak
      inhibition for saquinavir to very potent inhibition for ritonavir. Thus, they are
      predicted to have numerous drug interactions, although few such interactions have
      actually been documented either in pharmacokinetic studies or in clinical
      reports. This article reviews the published literature with an emphasis on the
      magnitude of interactions and on practical recommendations for management. Many
      of the drugs commonly taken by patients with HIV have a strong potential to
      interact with the protease inhibitors. In particular, the non-nucleoside reverse
      transcriptase inhibitors are also metabolised by CYPand have been shown to
      interact with protease inhibitors. Delaviridine is an inhibitor of CYP3A4, but
      nevirapine and efavirenz are inducers of CYP3A4. The protease inhibitors also
      interact with each other, and these interactions are being explored for their
      potential therapeutic benefits. Other commonly used drugs are also known to
      affect protease inhibitor metabolism, including inhibitors such as clarithromycin
      and the azole antifungals and inducers such as the rifamycins. Drugs that are
      known to be significantly affected by the protease inhibitors include
      ethinylestradiol and terfenadine; many other drugs have lesser or potential
      interactions. Although little specific data is available on the drug interactions
      of protease inhibitors, this lack of data should not be interpreted as a lack of
      interaction. Retrospective chart reviews have demonstrated that potentially
      severe drug interactions are frequently overlooked. Much more clinical data is
      needed, but pharmacists and physicians must always be vigilant for drug
      interactions, both those that are already documented and those that are
      predictable from pharmacokinetic profiles, in patients receiving protease
      inhibitors.

PMID- 10082074
TI  - Managing antipsychotic-induced tardive dyskinesia.
AB  - Antipsychotic-induced tardive dyskinesia is a common and clinically significant
      hazard of long term antipsychotic therapy. The arrival of atypical antipsychotics
      has markedly improved the outlook: atypical antipsychotics are emerging as
      effective treatments and may also reduce the prevalence and incidence of tardive
      dyskinesia. In mild cases, careful monitoring of tardive dyskinesia by serial
      Abnormal Involuntary Movements Scale (AIMS) assessments may be the appropriate
      course. More severe tardive dyskinesia calls for intervention in order to treat
      the dyskinesia. Atypical antipsychotics and tocopherol (vitamin E) are effective
      and generally well tolerated treatment options for tardive dyskinesia. Tardive
      dyskinesia variants such as tardive dystonia and tardive akathisia tend to be
      more severe and difficult to treat compared with typical tardive dyskinesia.
      Prevention of tardive dyskinesia is possible through careful selection of
      patients for antipsychotic therapy, use of the lowest effective antipsychotic
      dosages, use of atypical rather than traditional antipsychotics and concurrent
      tocopherol administration. The clinician can now undertake the management of
      tardive dyskinesia with growing confidence.

PMID- 10082073
TI  - Treatment of anxiety during pregnancy: effects of psychotropic drug treatment on
      the developing fetus.
AB  - Pregnancy is a time of great emotional change for a woman, producing increased
      stress and anxiety. Medication may be required for the treatment of anxiety
      disorders at this time. Given the fact that psychotropic drugs readily cross the
      placenta and could have important implications for the developing fetus, it is
      necessary to balance the possible effects of medication against the potential
      effects to both the mother and fetus if the anxiety disorder is left untreated.
      Despite the widespread use of psychotropic drugs such as benzodiazepines and
      antidepressants during pregnancy, there is a paucity of information regarding the
      effect of such exposure on the developing fetus. From a review of the literature
      it is clear that the issue of safety of psychotropic drugs during pregnancy is
      far from resolved. While some of the findings from animal studies are alarming,
      these studies cannot be directly extrapolated to humans. In addition, varying
      sample sizes and multiple drug exposures further complicate interpretation of
      human studies. Nonpharmacological treatments such as cognitive behavioural
      therapy should be employed whenever possible for the treatment of anxiety
      disorders during pregnancy. However, if medication is required pregnant women
      should be prescribed the lowest dosage for the minimum amount of time.

PMID- 10082075
TI  - Safety profile of Lansoprazole: the US clinical trial experience.
AB  - OBJECTIVE: Lansoprazole has undergone extensive clinical evaluation for the
      treatment of acid-peptic diseases. The aim of this study was to define the safety
      profile of lansoprazole and compare it to that of other therapeutic agents
      evaluated in the same controlled trials. METHODS: The clinical safety profile of
      lansoprazole and comparative agents (placebo, ranitidine and omeprazole) was
      reviewed for 3281 patients who participated in short term (up to 8 weeks) and
      long term (up to 56 months) clinical trials conducted in the US. Adverse events,
      laboratory value changes and gastric biopsy changes that occurred during
      treatment were compared statistically for differences between treatments.
      RESULTS: The incidence of adverse events and number of patients discontinuing
      treatment because of adverse events was similar for lansoprazole and comparative
      agents. Other than elevated serum gastrin levels, a known effect of proton pump
      inhibitors, no trends in laboratory changes were observed. Median values for
      gastrin levels remained within the normal range; about 2% of patients had gastrin
      levels >400 pg/ml at any time, while <1% had 2 or more gastrin values >500 pg/ml.
      Values returned to baseline levels after therapy was discontinued. No significant
      changes in gastric endocrine cell growth from baseline to final visit were
      observed, nor was there evidence of dysplasia or neoplasia. CONCLUSION:
      Lansoprazole is well tolerated for both short and long term treatment of acid
      related disease. The tolerability of lansoprazole is comparable to that of
      ranitidine, omeprazole and placebo in the treatment of these diseases.

PMID- 10082076
TI  - Pathophysiological role of calpain in experimental demyelination.
AB  - Calcium-activated neutral proteinase (calpain) has been extensively studied over
      the past three decades such that many enzymatic and structural properties of this
      enzyme are well understood. However, the pathophysiological roles of calpain
      remain poorly defined. In addition to recent studies delineating a role for
      calpain in various pathological conditions, this proteinase has been implicated
      in the degradation of myelin proteins in autoimmune demyelinating diseases such
      as multiple sclerosis and experimental allergic encephalomyelitis (EAE). In EAE,
      calpain translational expression is significantly increased in activated
      glial/inflammatory cells that participate in myelinolysis while calpain
      substrates (axonal and myelin proteins) are lost. Thus, since all major myelin
      proteins are calpain substrates, early studies suggest calpain may play an
      important role in demyelination of the central nervous system.

PMID- 10082077
TI  - Motor neuron degeneration is attenuated in bax-deficient neurons in vitro.
AB  - Apoptosis plays a major role in motor neuron survival during developmental cell
      death, after axotomy, and in motor neuron diseases. Bax is the first member of
      the bcl-2 family shown to promote apoptosis. In the present study, we used the
      bax-deficient mouse model to determine the role of bax in motor neuron survival
      in vitro by using dissociated spinal cord cultures. This system enables the
      maturation of individual motor neurons in a controlled in vitro environment.
      Motor neurons were identified by using the antineurofilament antibody SMI-32 and
      the antitranscription factor antibody Islet1. Both antibodies labeled large motor
      neurons in wild-type and bax-null cultures. Differentiated wild-type cultures
      exhibited a reduction in long-term cultures of two- and fivefold in the number of
      SMI-32- and Islet1-positive cells, respectively. The reduction in the number of
      motor neurons was attenuated in bax -/- cultures. Bax deficiency also attenuated
      serum withdrawal- and kainate-induced apoptosis in motor neurons. For comparison,
      necrotic cell death led to significant motor neuron cell death in both wild-type
      and bax -/- cultures. In addition, bax deficiency did not induce proliferation of
      motor neuron precursors in vitro. This study indicates for the first time that
      bax has a dominant role in the survival of long-term cultured motor neurons.

PMID- 10082078
TI  - Changes in phosphorylation of Ca2+/calmodulin-dependent protein kinase II
      (CaMKII) in processing of short-term and long-term memories after passive
      avoidance learning.
AB  - Characteristic autophosphorylation of calcium/ calmodulin-dependent protein
      kinase II (CaMKII) and its consequences have made this kinase an interesting
      target in studying the molecular pathway for important neuronal functions
      including learning and memory formation. In this article, we use
      immunoprecipitation and immunoblotting methods to detect changes in
      phosphorylation of CaMKII during memory formation in 1-day-old chicks trained in
      a single trial passive avoidance task. A 60-kDa protein has been
      immunoprecipitated from the chick brain with an anti-rabbit CaMKII antibody. This
      protein shows strong and specific immunoactivities with antibodies against the
      calmodulin binding site of CaMKII, and the N and C terminals of beta-CaMKII.
      Commercially available anti-phosphoserine and anti-phosphothreonine antibodies
      are shown to sensitively detect phosphorylation of purified CaMKII. The basal
      phosphorylation of CaMKII from the intermediate medial hyperstriatum ventrale
      (IMHV) and lobus parolfactorius (LPO) regions of the chick brain is shown to be
      largely right hemisphere-lateralized. When chicks are subjected to a passive
      avoidance training experience, a specific increase in CaMKII phosphorylation is
      induced in the IMHV and LPO of the left hemisphere from those chicks whose memory
      for the training experience is successfully retrieved. While this specific
      increase in CaMKII phosphorylation is seen in both the left IMHV and left LPO in
      short-term memory, it is detectable only in the left LPO associated with long
      term memory retrieval. The present results provide evidence that in vivo changes
      in phosphorylation of CaMKII are associated specifically with processing of
      distinct memory stages, which take place in specific brain regions.

PMID- 10082079
TI  - Gene transfer in astrocytes: comparison between different delivering methods and
      expression of the HIV-1 protein Nef.
AB  - To identify a good system to introduce foreign genes into normal and tumoral
      astrocytes, we studied the efficiency of two chemical methods, calcium phosphate
      precipitation and lipofection, and of a viral-mediated transfer by a vector
      derived from the highly attenuated modified vaccinia virus Ankara (MVA). Using
      the beta-galactosidase (beta-gal) gene (lacZ) as reporter, we searched for
      optimal experimental conditions to obtain an efficient gene transfer into human
      embryonic and neonatal rat astrocytes and into a human astrocytoma cell line
      (U373 MG). The beta-gal protein production was evaluated by cytochemical staining
      and enzymatic activity assay. Among chemical methods, lipofection was the most
      efficient system to transfect astrocytes in providing up to 60% of beta-gal
      positive cells in all the cell types analyzed. MVA infection also proved to be an
      efficient system to introduce heterologous genes into human embryonic astrocytes
      that appeared 80-100% positive 48-96 hr after an infection at a multiplicity of 1
      10. In contrast, only a limited infection was observed with rat astrocytes, human
      astrocytoma cells, and human leptomeningeal cells. A recombinant MVA vector
      expressing the human immunodeficiency virus-1 (HIV-1) regulatory protein Nef was
      used to transfect human embryonic astrocytes, and the resulting Nef expression
      was compared with that detected after lipofection in the same cells. By Western
      blot analysis, Nef expression was observed in human astrocytes 24-96 hr after
      infection and was similar to that present in stably HIV-1-infected astrocytoma
      cells. Lipofection resulted in lower Nef expression. In spite of these promising
      results, the negative effects of MVA infection on cell viability and the
      possibility that a productive infection occurs in human embryonic astrocytes
      limit the use of this vector for gene delivery in developmentally immature human
      glial cells.

PMID- 10082080
TI  - Role of central nervous system microvascular pericytes in activation of antigen
      primed splenic T-lymphocytes.
AB  - The cellular constituents of the blood-brain barrier (BBB) must make finely
      tuned, regulatory responses to maintain microvascular homeostasis. The mechanisms
      by which this task is accomplished are largely unknown. However, it is thought
      they involve a series of cross-talk mechanisms among endothelial cells (EC),
      pericytes (PC), and astrocytes. During inflammation, the BBB is exposed to a
      number of biological response modifiers including cytokines released by
      infiltrating leukocytes. The response to inflammatory cytokines may alter the
      normal regulatory function of EC and PC. These changes may account for some of
      the pathological findings in central nervous system (CNS) inflammatory disease.
      Previous studies have shown that PC and EC may have immune potential. We have
      investigated the response of the PC to a variety of inflammatory cytokines.
      Primary rat PC constitutively express low levels of intercellular adhesion
      molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I molecule,
      which can be upregulated in response to the cytokine interferon-gamma (IFNgamma).
      IFNgamma also induced the expression of MHC class II molecule. After induction of
      MHC class II molecule, CNS PC acquired the capacity to present antigen to primed
      syngeneic rat T-lymphocytes. Antigen presentation by PC was comparable to that
      seen with classic antigen-presenting cells. A small number of primary PC
      constitutively express low levels of vascular cell adhesion molecule-1 (VCAM-1),
      which was increased on exposure to tumor necrosis factor-alpha (TNFalpha).
      Results suggest that CNS PC respond to inflammatory cytokines, are involved in T
      lymphocyte activation, and express cell surface adhesion molecules (VCAM-1, ICAM
      1) that may provide costimulatory activity. It is likely that CNS PC are
      important in neuroimmune networks at the BBB.

PMID- 10082081
TI  - Human neurotropic JC virus early protein deregulates glial cell cycle pathway and
      impairs cell differentiation.
AB  - Progressive multifocal leukoencephalopathy (PML), a human demyelinating disease
      of the central nervous system (CNS), is induced upon replication of the human
      neurotropic virus, JCV, in glial cells. Similar to other polyomaviruses,
      replication of JCV is initiated and orchestrated by the viral early protein, T
      antigen, and results in the cytolytic destruction of oligodendrocytes, the subset
      of glial cells responsible for myelin production, and the appearance of bizarre
      astrocytic glial cells in affected individuals. Earlier results from studies in
      transgenic animals have suggested that in the absence of viral replication,
      expression of JCV T-antigen induces pathology consistent with hypomyelination of
      the brain. These observations suggest that JCV T-antigen has the ability to
      deregulate oligodendrocyte and perhaps astrocyte function in the CNS. Here we
      demonstrate that expression of JCV T-antigen in the bipotential glial cell line,
      CG-4, severely affects the ability of these cells to differentiate toward
      oligodendrocyte and astrocyte lineages as evidenced by their distinct
      morphological changes. Examination of the activity of cell cycle regulatory
      proteins including cyclins and their associated kinases reveals that in the
      absence of T-antigen, differentiation of CG-4 cells toward astrocytes and
      oligodendrocytes is accompanied by a decline in cyclin E, cdk2, cyclin A, and
      cyclin B activity. In contrast, cdc2 activity increased upon CG-4
      differentiation. In T-antigen-producing cells, distinct variations in the
      activity of several cyclins was observed. For example, while the activity of cdk2
      and cyclin E was enhanced in T-antigen expressing astrocytes compared to their
      levels in control cells, the activity of cdc2 was decreased in this cell type. In
      oligodendrocytes, expression of T-antigen decreased the activity of several
      cyclins and cdks including cyclin E and cdc2. On the other hand, the level of
      expression and activity of cyclin A was increased. Thus, it is evident that JCV T
      antigen deregulates several important cell cycle regulators during CG-4
      differentiation, and these alterations may contribute to the process of cell
      growth and differentiation in glial cells. The importance of our findings with
      regard to the neuropathogenesis of PML is discussed.

PMID- 10082082
TI  - Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors.
AB  - Dopamine (DA) release in the striatum is regulated by 5-hydroxytryptamine (5-HT,
      serotonin) through putative heteroreceptors. However, the effect of 5-HT is
      controversial. The present study investigated the effects of different 5-HT
      receptor ligands on DA release in the rat striatum by using in vivo microdialysis
      in conscious and freely moving rats. Perfusion with 5-carboxamidotryptamine,
      anpirtoline, pindobind-5-HT1A, and isamoltane demonstrated the involvement of 5
      HT1A and 5-HT1B receptors in facilitating DA release. In contrast, 5-HT2
      receptors mediated inhibition of DA efflux, as shown by experiments with DOI [R-(
      )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and ketanserin. A 5-HT3 agonist
      (1-(m-chlorophenyl)-biguanide hydrochloride) did not have any effect. None of the
      agonists used affected DA uptake into striatal synaptosomes. Unilateral 6
      hydroxydopamine lesioning of the nigrostriatal DA pathway led to a selective
      decrease in 5-HT2 receptors. It is concluded that there are 5-HT2 heteroreceptors
      at the dopaminergic terminals that mediate inhibition of DA release. Further
      investigation is required to clarify the localization of the 5-HT1 receptors in
      the striatum.

PMID- 10082083
TI  - Extracellular single-unit recordings of piriform cortex neurons in rats:
      influence of different types of anesthesia and characterization of neurons by
      pharmacological manipulation of serotonin receptors.
AB  - In epilepsy research, there is a growing interest in the role of the piriform
      cortex (PC) in the development and maintenance of limbic kindling and other types
      of limbic epileptogenesis leading to complex partial seizures. Neurophysiological
      studies on PC or amygdala-PC slice preparations from kindled rats showed that
      kindling of the amygdala induces long-lasting changes in synaptic efficacy in the
      ipsilateral PC, including spontaneous discharges and enhanced susceptibility of
      PC neurons to evoked burst responses. These long-lasting electrophysiological
      changes in the PC during kindling appear to be due, at least in part, to impaired
      function of gamma-aminobutyric acid (GABA)ergic interneurons. The aim of the
      present study was to develop an anesthetic protocol allowing electrophysiological
      single-unit recordings from inhibitory, presumably GABAergic PC interneurons in
      vivo. In addition to recording of spontaneously active PC neurons,
      microiontophoretic application of glutamate was used to activate silent neurons.
      Anesthesia of rats with ketamine/xylazine was not suited for single-unit
      recordings in the PC because of marked cardiovascular depression. Anesthesia with
      chloral hydrate allowed recording of spontaneous or glutamate-driven single-unit
      activity in approximately 40% of all animals. A similar percentage was obtained
      when recordings were done with the narcotic opioid fentanyl (plus gallamine),
      after all surgical preparations were performed under anesthesia with repeated
      administration of the barbiturate methohexital. To avoid brain accumulation of
      methohexital by repeated applications, we modified the anesthetic protocol in
      that methohexital was only injected once for initiation of surgical anesthesia,
      followed by the short-acting anesthetic propofol which does not accumulate upon
      repeated application. Again, after surgical preparation, electrophysiological
      recordings were done under fentanyl (plus gallamine). By this procedure,
      spontaneous or glutamate-driven single-unit activity could be measured in all
      rats in either layer II or III of the PC. Based on shape and frequency of action
      potentials, two types of neurons were recorded. The predominant type was similar
      in its firing characteristics to GABAergic neurons in other brain regions, was
      mainly located in layer III, and could be suppressed by the serotonin2A receptor
      antagonist MDL 100,907, suggesting that this type of PC neuron represents
      inhibitory, putative GABAergic interneurons. This new in vivo preparation may be
      useful for evaluation of PC neurons in kindled rats.

PMID- 10082084
TI  - Characterization and time course of MPP+ -induced apoptosis in human SH-SY5Y
      neuroblastoma cells.
AB  - A genetic defect in complex I of the mitochondrial electron transport chain (ETC)
      is implicated in the etiology of Parkinson's disease (PD), and has been studied
      in hybrid mitochondrial transgene cells based on the SH-SY5Y neuroblastoma. We
      sought to characterize further the mechanisms and time course of cell death in
      cultures of human SH-SY5Y neuroblastoma cells exposed to the ETC complex I
      inhibitor methylpyridinium ion (MPP+). We verify previous reports that apoptosis
      occurs after MPP+ exposure in SH-SY5Y cells. Nuclear pyknosis, the end stage of
      apoptosis, is evident after 18-hr exposure to 5 mM MPP+ and reversible until 10
      hr, providing a temporal window within which to look for molecular and
      physiological correlates of MPP+-induced apoptosis. We then looked for
      mitochondrial correlates of MPP+ induced apoptosis in SH-SY5Y cells. Using flow
      cytometry, we found that MPP+ -induced increased reactive oxygen species (ROS)
      and lactate production consistent with inhibition of the ETC. Rho(o) cells,
      lacking a functional ETC, showed no ROS production, compensatory lactate
      production or apoptosis after exposure to MPP+. Finally, we show a collapse in
      ROS production and mitochondrial potential that is temporally correlated with
      irreversibility of MPP+ -induced apoptosis.

PMID- 10082085
TI  - Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD
      human amyloid precursor protein gene expression.
AB  - We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h
      APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We
      were able to infect PC12 cells with very high efficiency because approximately
      90% of the cells were cytochemically positive for beta-galactosidase activity
      when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells
      infected with adenovirus containing h-APP cDNA showed high-level transcription
      and expression of h-APP as measured by reverse transcriptase-polymerase chain
      reaction and Western immunoblot analyses, respectively. Intracellular and
      extracellular levels of h-APP were elevated approximately 17-and 24-fold in
      cultures infected with recombinant adenovirus containing wild-type mutant and 13-
      and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures
      infected with antisense h-APP or null adenovirus. H-APP levels were maximal 3
      days after infection. Overexpression of V642F mutant h-APP in PC12 cells and
      hippocampal neurons resulted in about a twofold increase in death compared with
      overexpression of wild-type h-APP. These results demonstrate the usefulness of
      recombinant adenoviral mediated gene transfer in cell culture studies and suggest
      that overexpression of a familial Alzheimer's disease mutant APP may be toxic to
      neuronal cells.

PMID- 10082086
TI  - Species differences in fodrin proteolysis in the ischemic brain.
AB  - There has been growing evidence that the breakdown of cytoskeletal proteins is an
      important biochemical change leading to ischemic neuronal death. In the present
      study, we investigated species differences in the susceptibility of fodrin to
      calpain activation induced by cerebral ischemia in gerbils, rats, and mice. In
      vivo fodrin proteolysis and degradation of microtubule-associated protein 2 after
      complete ischemia occurred more rapidly in the hippocampus and cerebral cortex of
      the gerbil brain than in the corresponding area of the rat and mouse brain. The N
      methyl-D-aspartate (NMDA) receptor antagonist MK-801 injected intraperitoneally
      before ischemia did not diminish fodrin degradation in the gerbil hippocampus. In
      vivo fodrin proteolysis was inhibited at 33 degrees C and enhanced at 41 degrees
      C compared with proteolysis at 37 degrees C during ischemia. However, in vitro
      fodrin proteolysis after addition of Ca2+ into the crude membrane fraction did
      not show any differences among three species. Although it is highly unlikely that
      the difference in the sensitivity of NMDA receptor or the sensitivity of calpain
      activation to calcium was the crucial determinant of susceptibility of fodrin
      degradation in the gerbil brain, the present study clearly demonstrated that
      fodrin in the gerbil brain was more susceptible to calpain activation induced by
      ischemia than that in the rat and mouse brains. Enhanced proteolysis may be one
      of the reasons neurons in the gerbil brain are highly vulnerable to ischemia.

PMID- 10082087
TI  - Expression of doublecortin correlates with neuronal migration and pattern
      formation in diverse regions of the developing chick brain.
AB  - The development of functional layers in the brain involves spatially and
      temporally regulated gene expression. Through cDNA library screening, we have
      identified genes that are expressed in a neural-specific manner during brain
      development. Sequencing and expression data indicate that one of the clones,
      18C15, is the chick homologue of doublecortin, a human X-linked gene found to be
      mutated in subcortical laminar heterotopia (double cortex syndrome) and
      lissencephaly. The 18C15 mRNA contains multiple motifs that are known to regulate
      mRNA stability in response to inductive signals, and these motifs are conserved
      between the chick and human sequences. Doublecortin is found to be expressed at
      peak levels during early development of the cerebellum and forebrain, and is
      expressed in other regions including the tectum, spinal cord, and dorsal root
      ganglia. This study demonstrates both spatial and temporal regulation of
      doublecortin expression in the chick, which is associated with early events in
      brain development, including neuronal migration.

PMID- 10082088
TI  - Continuous EEG monitoring in the intensive care unit: early findings and clinical
      efficacy.
AB  - The assessment of the neurocritical care patient involves serial assessment of
      neurologic status using bedside clinical examination and a variety of periodic
      neurophysiologic testing. Continuous electroencephalographic (CEEG) monitoring in
      the intensive care unit offers a unique means to track neurologic function
      directly and regionally. CEEG is becoming more widespread with a growing but
      small body of literature. The purpose of this paper is to outline the current
      experience with intensive care unit CEEG monitoring. The basic methods and
      caveats are discussed. We review the underlying rationale for using CEEG which is
      that secondary neurologic injury commonly occurs in the intensive care unit and
      at times is hard to detect. CEEG has a proven role in detecting secondary
      injuries, namely seizures and brain ischemia. The basic tenets of establishing
      clinical effectiveness for CEEG in the ICU are discussed while acknowledging a
      need for further study of clinical effectiveness. We review our initial clinical
      experience of CEEG in 300 patients and outline the clinical efficacy in terms of
      cost reduction and improvement in outcome (P < 0.01) using CEEG. Finally, several
      controversial aspects of CEEG are enumerated, and the need for additional study
      to answer these pressing questions is presented.

PMID- 10082089
TI  - Continuous EEG monitoring in the neuroscience intensive care unit and emergency
      department.
AB  - This article reviews established, emergent, and potential applications of
      continuous EEG (CEEG) monitoring in the Neuroscience Intensive Care Unit (NICU)
      and Emergency Department. In each application, its goal as a neurophysiologic
      monitor is to extend our powers of observation to detect abnormalities at a
      reversible stage and to guide timely and physiologically sound interventions.
      Since this subject was reviewed 5 years ago, the use of CEEG monitoring has
      become more widespread. In a modern NICU, it is no longer novel to have CEEG data
      contributing to management decisions. A well-trained CEEG monitoring team is
      important for its optimal implementation. In the diagnosis and management of
      convulsive and nonconvulsive status epilepticus, its value appears established.
      It is finding benefit in the early diagnosis and management of precarious
      cerebral ischemia, including severe acute cerebral infarctions and post-SAH
      vasospasms. In comatose patients, it can provide diagnostic and prognostic
      information which is otherwise unobtainable. More recently, it has been found
      advantageous for targeting management of acute severe head trauma patients.
      Networking technology has facilitated the implementation and oversight of CEEG
      monitoring and promises to expand its availability, credibility, and
      effectiveness. The maturing of CEEG use is reflected in preliminary efforts to
      assess its cost benefit, cost effectiveness, and impact on patient outcomes.

PMID- 10082090
TI  - EEG monitoring in the intensive care unit: pitfalls and caveats.
AB  - Electroencephalogram monitoring is a valuable means of monitoring thalamocortical
      function in the comatose, sedated, or paralyzed patient in the intensive care
      unit. The following problems arise especially with long-term recordings that are
      beyond those experienced in the standard EEG laboratory: 1) faulty electrodes,
      either single- or multiple-scalp electrodes or ground or reference electrodes; 2)
      connections of electronic equipment; 3) induced artifacts from electronic devices
      and nonelectronic equipment; 4) electrode placement issues; and 5) biologic,
      including movement-related, artifacts. Continuous quality improvement strategies
      should be implemented to minimize problems. Prompt troubleshooting and regular
      review sessions are two important components.

PMID- 10082091
TI  - Succinylcholine induced hyperkalemia and cardiac arrest death related to an EEG
      study.
AB  - Changes in EEGs during cardiac arrest have been described in detail by many
      authors; however, mortality because of an EEG has never been reported. The
      authors report the case of a patient who developed cardiac arrest causally
      related to administration of succinylcholine for reduction of excessive amounts
      of myogenic artifact during an EEG. This case indicates the need for caution when
      doing an EEG study in an intensive care unit setting.

PMID- 10082092
TI  - Generalized periodic epileptiform discharges: etiologies, relationship to status
      epilepticus, and prognosis.
AB  - Generalized periodic epileptiform discharges (GPEDs) are generalized, synchronous
      electrographic discharges. This study investigates etiologies, relationship to
      status epilepticus (SE), and the prognosis for patients with GPEDs. All EEGs with
      GPEDs performed at Duke University Medical Center between January 1994 and
      October 1995 were identified. Clinical histories and EEGs were reviewed. They
      were divided into groups depending on the etiology of the GPEDs, whether the
      patients were in SE or not, and whether they were alive or not at discharge. A
      comparison of histories and GPED characteristics among groups was undertaken
      using parametric and nonparametric t tests. Twenty-five patients were enrolled: 7
      (28%) had toxic-metabolic encephalopathy, 10 (40%) had anoxia and toxic-metabolic
      encephalopathy, and 8 (32%) had a primary neurologic process. Eight patients
      (32%) were in SE. In the SE group, GPED amplitude was higher (110 versus 80
      microV, P < 0.05), GPED duration was longer (0.5 versus 0.3 seconds, P < 0.05),
      and inter-GPED amplitude was higher (34 versus 17 microV, P < 0.05). Nine
      patients (36%) were alive at discharge; they were more likely to be younger (51
      versus 68 years, P < 0.05), have a better mental status at the time of their EEG,
      and have a higher inter-GPED amplitude (33 versus 18 microV, P < 0.05). A variety
      of conditions, including SE, can cause GPEDs. Intergroup differences in historic
      and GPED features exist between those patients in SE and those not in SE and
      those with good and poor prognoses.

PMID- 10082093
TI  - An automated system for epileptogenic focus localization in the
      electroencephalogram.
AB  - This paper describes an automated system for the detection and localization of
      foci of epileptiform activity in the EEG. The system detects sharp EEG transients
      (STs) in the process, but the emphasis is on epileptic focus localization. A
      combination of techniques involving signal processing, pattern recognition, and
      the expert rules of an experienced electroencephalographer, involving
      considerable spatiotemporal context information, is applied to multichannel EEG
      data. An overall emphasis on minimizing the number of false-positive sharp
      transient detections drives the system design. Tested on data from 13 subjects
      with epileptiform activity and 5 controls, all areas of focal epileptiform
      activity were detected by the system, although not all of the contributing foci
      were reported separately. Two false-positive foci were detected as well due to
      nonfocal spike activity and normal spike-like activity not present in the
      training set. The system detected 95.7% of the epileptiform events constituting
      the correctly detected foci, with a false detection rate of 11.1%.

PMID- 10082094
TI  - Origin of the "N10" stationary-field potential after median nerve stimulation.
AB  - The scalp far-field potentials after median nerve stimulation at the wrist
      consist of P9, P11, P13, and P14 positive components. Earlier, Emerson et al.
      (1984) identified the "N10" negative potential in-between the P9 and P11 and
      claimed that this was not merely a passive return to the baseline after the P9
      positive deflection but a distinct component reflecting a proximal brachial
      plexus volley. They thought N10 was a far-field potential having widespread
      distribution with a fixed latency. In this study we found that N10 was of higher
      amplitude after median nerve stimulation at the elbow than after stimulation at
      the wrist. Indeed the N10 latency was fixed from the lower anterior neck to the
      scalp, and its amplitude was maximum at the anterior lower neck. The latency of
      N10 was about 0.3 milliseconds longer than the Erb's potential and 0.15
      milliseconds longer than the potential recorded from the lateral neck on the side
      of stimulation. The N10 amplitude increased in parallel with increased stimulus
      intensity. In order to explore the origin of the N10 stationary field potential,
      we designed a paired stimuli paradigm applied to the wrist (S1) and to the elbow
      (S2). The interstimulus interval between S and S2 was adjusted so that the timing
      of S2 was immediately after the traveling impulse produced by the S1 stimulus as
      it passed through the S2 stimulus site. This technique allowed stimulation of the
      anterior interosseous nerve selectively at the elbow while the median nerve
      originating from the wrist was undergoing refractory period. The response of (S1
      + S2) - S1 showed only the N10 with absence of cervical and cortical responses,
      implying that N10 was activated, predominantly by the interosseous nerve, i.e.,
      an antidromic motor volley, when the median nerve was stimulated at the elbow.

PMID- 10082095
TI  - Traumatic brain injury assessed with olfactory event-related brain potentials.
AB  - Olfactory event-related potentials (OERPs) were evaluated to develop an
      objective, quantitative assessment of sensory and cognitive olfactory loss
      following traumatic brain injury (TBI). Subjects included 25 TBI patients and 25
      age/gender-matched healthy controls. Following standard clinical evaluation of
      smell function, TBI patients were divided into three groups: 12 anosmics (loss of
      smell), 6 hyposmics (reduced smell), and 7 normosmics (normal smell). Cognitive
      ability was assessed using the Trail Making Test (A and B). OERPs were recorded
      monopolarly from midline electrode sites using an amyl acetate stimulus with a 60
      second interstimulus interval; subjects estimated the magnitude of each odor
      stimulus. Anosmic TBI patients were also tested with OERPs using ammonia to
      ensure trigeminal nerve function. Amyl acetate OERPs demonstrated that the
      sensory N1 and P2 amplitudes and the cognitive P3 amplitudes were absent in the
      anosmic TBI patients and greatly reduced in the hyposmic and normosmic TBI
      patients compared to healthy controls. The trigeminal OERPs from the anosmic TBI
      patients were within normal limits, indicating that the primary olfactory
      deficits were objectively measured with OERPs. The relationship between the OERPs
      and neuropsychologic test performance supports the cognitive loss associated with
      TBI. The present study lends support to the utility of OERPs as an objective tool
      for measuring sensory and cognitive loss after traumatic brain injury.

PMID- 10082096
TI  - The US Food and Drug Administration investigational device exemptions and
      clinical investigation of cardiovascular devices: information for the
      investigator.
AB  - The conduct of a clinical investigation of a medical device to determine the
      safety and effectiveness of the device is covered by the investigational device
      exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to
      the extent consistent with the protection of public health and safety and with
      ethical standards, the discovery and development of useful devices intended for
      human use, and to that end to maintain optimum freedom for scientific
      investigators in their pursuit of this purpose." Conducting a clinical
      investigation may require an approved IDE application. The US Food and Drug
      Administration encourages early interaction with the agency through the pre-IDE
      approval process during the development of a device or technology and during the
      preparation of an IDE application. This facilitates approval of the IDE
      application and progression into the clinical investigation. This paper reviews
      the terminology and applicability of the IDE regulation and the type of study
      that requires an IDE application to the Food and Drug Administration. The pre-IDE
      approval process and the development of an IDE application for a significant risk
      study of a cardiovascular device are discussed.

PMID- 10082097
TI  - Dialysis graft declotting with very low dose urokinase: is it feasible to use
      "less and wait?".
AB  - PURPOSE: "Lyse and wait" dialysis graft declotting is simple and effective, but
      the minimum necessary dose of urokinase is unknown. The efficacy of the technique
      with very low dose urokinase is evaluated. MATERIALS AND METHODS: Twenty-one
      grafts in 17 patients were declotted with use of the lyse and wait technique, but
      with 5,000-15,000 U of urokinase initially. Graft angiography was performed when
      an interventional suite was available. Declotting was completed in the manner
      chosen by the individual operator. Angiograms, interventional radiology records,
      and dialysis records were reviewed. RESULTS: Technical and clinical success were
      achieved in 95% of cases. Mean initial urokinase dose was 6,667 U. Initial
      angiography was performed at a mean 86 minutes. Two cases required second 5,000-U
      boluses to achieve complete graft thrombolysis. In all other cases, complete or
      near complete graft thrombolysis was observed with the initial very low dose. No
      bleeding, arterial embolic, or pulmonary embolic complications were observed.
      CONCLUSIONS: Doses of urokinase as low as 5,000 U are effective for lyse and wait
      declotting. A substantial reduction in drug costs can be expected with the "less
      and wait" modification. Bleeding risk may also be reduced.

PMID- 10082098
TI  - Angioplasty and bolus urokinase infusion for the restoration of function in
      thrombosed Brescia-Cimino dialysis fistulas.
AB  - PURPOSE: To evaluate the use of urokinase and angioplasty in treatment of
      thrombosed Brescia-Cimino fistulas. MATERIALS AND METHODS: From January 1994 to
      April 1997, 17 patients (10 women and seven men; age range, 17-78 years; mean 54
      years) with complete thrombosis of their Brescia-Cimino fistulas were referred to
      our department for thrombolysis and angioplasty. Thrombosis of the fistula had
      occurred within 24 hours of attempted thrombolysis in 11 patients and between 24
      and 72 hours in six patients. Urokinase was given as a bolus into the fistula,
      and heparin was administered into the central venous vasculature. Angioplasty was
      performed at the arterial inflow and the fistula itself. RESULTS: Procedural
      success was 82% (14 of 17 patients). Primary patency was 71% at 6 months and 64%
      at 12 months. Primary assisted patency was 93% at 6 and 12 months. Secondary
      patency was 100% at 6 and 12 months. One fistula thrombosed within 24 hours of
      the initial procedure, and a repeat procedure was successfully performed. All
      other fistulas have remained patent with a maximum follow-up of 40 months
      (average function of 16 months). Two patients have died of unrelated causes. One
      Wallstent was deployed for treatment of an angioplasty-induced venous rupture.
      CONCLUSION: Long-term function of Brescia-Cimino fistulas after thrombolysis and
      angioplasty is excellent with patency rates similar to those of newly placed,
      mature Brescia-Cimino fistulas.

PMID- 10082099
TI  - Long-term follow-up of Vena Tech-LGM filter: predictors and frequency of caval
      occlusion.
AB  - PURPOSE: To report the frequency of caval occlusion after Vena Tech-LGM filter
      placement and identify related factors and their potential clinical significance.
      MATERIALS AND METHODS: The filter was inserted into 243 patients, 142 of whom met
      inclusion criteria for this prospective study. Follow-up examinations performed
      every 2 years included clinical evaluation, plain frontal radiography of the
      abdomen, duplex scanning of the inferior vena cava (IVC), and/or
      phlebocavography. RESULTS: A progressive decrease in IVC patency was observed,
      reaching 66.8% at 9 years of follow-up. Complete caval occlusion occurred in 28
      patients and was significantly (P < 10(-6)) associated with retraction in 24
      cases. Caval occlusion was not related to age, sex, pulmonary embolism (PE), deep
      venous thrombosis level, underlying conditions predisposing to a thromboembolic
      disease before filter insertion, the level of filter placement, use of
      anticoagulant therapy, and death during follow-up. PE with anticoagulation
      failure was a predictive factor (P = .016) of subsequent filter occlusion during
      follow-up as compared to all other clinical indications for filter placement.
      Filter patency at 9 years of follow-up was 35.2% in the PE group with
      anticoagulation failure and 80% for other patients (odds ratio, 2.5; 95%
      confidence interval 1.16-5.4). CONCLUSION: PE with anticoagulation failure was
      the only factor predictive of subsequent caval occlusion observed in patients
      after Vena Tech-LGM filter placement. Caval occlusion was also related to Vena
      Tech-LGM filter retraction, which usually occurred at the time of occlusion.

PMID- 10082100
TI  - Determination of inferior vena cava diameter in the angiography suite: comparison
      of three common methods.
AB  - PURPOSE: Significant inferior vena cava (IVC) filter migration has been
      associated with deployment of some filter types in IVCs measuring more than 28 mm
      in diameter at inferior vena cavography. The purposes of this study were to (a)
      determine if significant differences exist between IVC measurements obtained
      using a gold standard technique and two other widely accepted methods, and (b) if
      differences exist, how often do these differences cause incorrect IVC sizing
      around a diameter of 28 mm, with its associated filter migration issues.
      MATERIALS AND METHODS: One hundred thirteen consecutive inferior vena cavograms
      were retrospectively reviewed. The transverse diameter of the infrarenal IVC was
      determined by using a calibrated intravascular catheter (the gold standard),
      subtraction of 20% from the measured transverse IVC diameter on a cut-film
      radiograph, and a radiopaque ruler placed immediately posterior to the patient.
      RESULTS: The concordance correlation of the 20% magnification method versus
      internal calibration was 0.94. Kappa analysis to determine agreement at a
      diameter of 28 mm yielded a Kappa coefficient of 0.490. The concordance
      correlation of an external ruler versus internal calibration was 0.43, with a
      Kappa coefficient of 0. CONCLUSION: The poor Kappa correlations for both methods
      demonstrate that they are unreliable in identifying megacava. Inferior vena
      cavography prior to IVC filter placement should be performed with a calibrated
      intravascular catheter.

PMID- 10082101
TI  - Sharp recanalization of central venous occlusions.
AB  - PURPOSE: To describe a sharp puncture technique for recanalization of chronic
      central venous occlusions that could not be traversed by a guide wire. MATERIALS
      AND METHODS: Five patients presented with six longstanding central venous
      occlusions that could not be traversed with a guide wire after thrombolysis. The
      occlusions occurred following radiation for lung carcinoma (n = 2) and indwelling
      venous catheters (n = 4). The length of venous occlusion was determined by
      simultaneously advancing transbrachial and transfemoral catheters to the site of
      occlusion. Initially, a curved guiding catheter with a Rosch-Uchida needle and,
      in subsequent patients, a coaxial sheathed needle with a 21-gauge stylet were
      used for recanalization. The recanalized veins were then balloon dilated and
      stents were placed. RESULTS: With use of this technique, recanalization was
      successful in five of the six occlusions. One occlusion was too long to traverse
      safely in one patient. Two patients were asymptomatic 16-18 months after the
      recanalization. CONCLUSION: This new technique offers an effective alternative to
      surgery in the treatment of central venous occlusion.

PMID- 10082102
TI  - Use of endothelial cells containing superparamagnetic microspheres to improve
      endothelial cell delivery to arterial surfaces after angioplasty.
AB  - PURPOSE: The purpose of this study was to determine if the luminal surface of
      balloon-dilated arteries can be re-endothelialized circumferentially with use of
      normal endothelial cells (ECs) and superparamagnetic microsphere-containing
      endothelial cells (MagECs) to cover gravity-dependent and independent arterial
      surfaces, respectively. MATERIALS AND METHODS: MagECs were obtained after
      phagocytosis of albumin-coated superparamagnetic polystyrene microspheres by
      rabbit microvascular ECs. The effect of microsphere internalization on cell
      adhesion was determined in vitro by comparing ECs and MagECs in terms of time
      courses of adhesion to fibronectin and cell retention after exposure to a shear
      stress. In vivo re-endothelialization was performed by delivering fluorescently
      labeled ECs and MagECs to a balloon-dilated artery with a double-balloon
      catheter, placing a magnet over the artery, and rotating the rabbit axially.
      Endoluminal coverage of arterial cross-sections was estimated by epifluorescence
      microscopy. RESULTS: Under the influence of gravity, in vitro cell adhesion to
      fibronectin after 5, 10, and 15 minutes was similar for the ECs (34%, 74%, and
      70%) and MagECs (40%, 56%, and 93%). In vitro cell retention after exposure to a
      shear stress (25 dynes/cm2) was greater (P < .05) for ECs than for MagECs (82% vs
      69%). Use of ECs plus MagECs in vivo resulted in cell delivery that was nearly
      circumferential. CONCLUSIONS: Delivery of a mixture of ECs and MagECs in
      combination with animal rotation and a magnetic field provide nearly
      circumferential delivery of ECs to the luminal surface of balloon-dilated
      arteries. The presence of superparamagnetic microspheres in cells does not impede
      cell adhesion but does decrease cell retention after exposure to a fluid shear.

PMID- 10082103
TI  - Microcatheter adhesion of cyanoacrylates: comparison of normal butyl
      cyanoacrylate to 2-hexyl cyanoacrylate.
AB  - PURPOSE: To compare the catheter adhesion properties of 2-hexyl cyanoacrylate
      (Neuracryl M), a new agent, to those of normal butyl cyanoacrylate (Histoacryl),
      the most widely used liquid acrylic agent for microcatheter embolization.
      MATERIALS AND METHODS: 2-hexyl cyanoacrylate (Neuracryl M1) was tested in pure
      form and mixed with either a proprietary polymerization retardant/contrast agent
      (Neuracryl M2) or ethiodized oil (Ethiodol). Histoacryl was tested in pure form
      and mixed with Ethiodol. The cyanoacrylate mixtures were injected through
      microcatheters into wells partially filled with heparinized whole blood. The
      cyanoacrylates were allowed to polymerize around the microcatheter tips for 1-3
      minutes. The microcatheters were then pulled at a constant rate until they were
      extracted from the polymerized cyanoacrylates. The peak forces required for
      extraction were recorded. RESULTS: The peak forces required to extract the
      microcatheters from either pure Histoacryl or Histoacryl mixed with 33% Ethiodol
      were significantly higher (P < .01; P < .05) than those for pure Neuracryl M1.
      When Neuracryl M1 and M2 were mixed together (as intended for clinical use), the
      force required for microcatheter extraction was significantly lower than that for
      either pure Histoacryl, Histoacryl mixed with 33% Ethiodol, or Neuracryl M1 alone
      (P < .01; P < .01; P < .01, respectively). The force required to extract
      microcatheters from the Neuracryl M1 and M2 mixture was not, however,
      significantly different from that of Histoacryl mixed with 50% Ethiodol. The
      force of extraction for the Neuracryl M1 and 50% Ethiodol mixture was below our
      ability to obtain precise measurements. CONCLUSION: When Neuracryl M1 was mixed
      with its proprietary polymerization retardant/contrast agent (Neuracryl M2),
      catheter adhesion was not significantly different from that of Histoacryl mixed
      with 50% Ethiodol, a mixture common in clinical use. When Neuracryl M1 was tested
      alone or mixed with Ethiodol (not intended by the manufacturer), catheter
      adhesion was significantly decreased relative to pure Histoacryl or equivalent
      mixtures of Histoacryl and Ethiodol.

PMID- 10082104
TI  - Patent ductus arteriosus masquerading as traumatic aortic rupture at aortography:
      the complementary role of transesophageal echocardiography.

PMID- 10082105
TI  - Treatment of gastroduodenal artery hemorrhage with a conventional stent.

PMID- 10082106
TI  - Gadolinium-enhanced breathhold three-dimensional time-of-flight renal MR
      angiography in the evaluation of potential renal donors.
AB  - PURPOSE: To evaluate the utility of gadolinium-enhanced three-dimensional (3D)
      time-of-flight (TOF) magnetic resonance angiography (MRA) of the renal arteries
      in the evaluation of potential renal donors. MATERIALS AND METHODS: Fifty
      consecutive patients underwent gadolinium-enhanced 3D-TOF MRA of the renal
      arteries as part of their evaluation as possible renal donors. All imaging was
      performed on a 1.5-T system with use of a torso phased-array coil. Conventional
      T1-weighted axial spin-echo and T2-weighted axial fast spin-echo imaging was
      performed to evaluate the renal parenchyma. Coronal dynamic MRA was performed
      during bolus injection of 40 mL of gadolinium with use of a 3D-TOF sequence
      requiring a breathhold of approximately 30 seconds. Maximum-intensity-projection
      reconstructions were obtained of the renal arterial and venous anatomy. All
      studies were prospectively evaluated by a single radiologist experienced with
      body MRA. Intraoperative findings were used as the reference standard in 35
      patients. To evaluate interobserver variability, each examination was evaluated
      for image quality, renal artery number, and anatomy by two radiologists
      experienced with MRA and blinded to the other's interpretations and surgical
      results. RESULTS: Ninety-eight percent of all MRAs were graded as diagnostic
      quality (Kappa value = 0.38; P < .05). Multiple renal arteries were identified in
      29 (29%) of 100 kidneys. Four of 50 patients studied (8%) had renal parenchymal
      abnormalities identified with MR imaging. Sensitivity and specificity for
      accessory renal artery detection was 71% and 95%, respectively. Overall, accuracy
      for MRA in determining renal artery number was 90%. CONCLUSION: Gadolinium
      enhanced breathhold 3D-TOF renal MRA is sufficient to assess the renal arteries
      in potential donors.

PMID- 10082107
TI  - High occlusion rate in experimental transjugular intrahepatic portosystemic shunt
      created with a Dacron-covered nitinol stent.
AB  - PURPOSE: To assess whether the use of a prosthesis covered by a Dacron sheath
      might prevent pseudointimal hyperplasia in a transjugular intrahepatic
      portosystemic shunt (TIPS). MATERIALS AND METHODS: A TIPS procedure was performed
      in nine pigs, after creation of a portal vein microembolization model of portal
      hypertension, by using a Dacron-covered nitinol stent. The first centimeter on
      the lower extremity of this specially made prototype was uncovered, to avoid
      portal vein thrombosis. Three weeks later, the seven surviving animals underwent
      transjugular hemodynamic and angiographic follow-up and were then killed for
      gross and histologic evaluation. RESULTS: Shunt insertion was possible in all
      pigs; two died of complications of the procedure. After 3 weeks only two shunts
      were patent, although a 50%-60% narrowing of the initial portion of the shunt was
      present; the remaining shunts were occluded. Histologic examination showed
      pseudointimal hyperplasia associated, in the cases of occlusion, with a luminal
      thrombosis. CONCLUSION: This Dacron-covered stent did not prevent pseudointima
      formation over the stent and resulted in a high early occlusion rate, probably
      related to a pronounced tissue fibrotic response likely due to Dacron-induced
      inflammation.

PMID- 10082108
TI  - Three-dimensional sonographic guidance for transvenous intrahepatic invasive
      procedures: feasibility of a new technique.

PMID- 10082109
TI  - Outcome and safety of transrectal US-guided percutaneous cryotherapy for
      localized prostate cancer.
AB  - OBJECTIVES: To assess the effectiveness and safety of ultrasound (US)-guided
      cryotherapy as a primary treatment for localized prostate cancer. MATERIALS AND
      METHODS: A prospective study of percutaneous transrectal US (TRUS)-guided
      cryotherapy was performed on 71 patients with T1-T3, N0, M0 prostatic cancer: 10
      patients underwent two or more procedures. All cases were newly diagnosed and
      patients had no previous treatment for cancer. For all patients, TRUS biopsies
      were performed at 5-6 months. Patients were monitored at 6 weeks; 3, 6, 9, and 12
      months; and twice yearly thereafter for prostate specific antigen (PSA) levels,
      complications, and clinical evidence of residual disease. RESULTS: Follow-up from
      10 to 36 months was available for 70 of 71 patients; one patient died of
      unrelated disease. Initially, 10 of 69 patients had positive postcryotherapy
      biopsy results. After repeated treatment, nine of these 10 patients had negative
      biopsy results and one patient had no follow-up. Overall, 68 of 69 patients had
      negative biopsy results. At 1 year, 43 of 64 (67%) had an undetectable PSA level.
      Two patients had proven metastases. Complications include three cases with
      urethral sloughing requiring transurethral resection of the prostate (TURP). One
      patient had orchitis. Two patients had persistent incontinence, one as the result
      of a TURP. There was no death, acute serious morbidity, or fistula formation.
      Impotence was universal at 6 months, but many patients demonstrated late
      recovery. CONCLUSION: Cryoablation is an imaging-guided percutaneous intervention
      for prostate cancer that can safely yield disease-free status in a high
      percentage of patients with localized disease.

PMID- 10082110
TI  - Deformation and migration of Palmaz stents after placement in the
      tracheobronchial tree.

PMID- 10082111
TI  - Single-step dilation for large-bore percutaneous gastrostomy and
      gastrojejunostomy.

PMID- 10082112
TI  - Antibiotic prophylaxis.

PMID- 10082113
TI  - Flow redistribution during uterine artery embolization for the management of
      symptomatic fibroids.

PMID- 10082114
TI  - HLA class I homozygosity accelerates disease progression in human
      immunodeficiency virus type 1 infection.
AB  - Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte
      responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly,
      homozygosity at class I loci can reduce the repertoire for such HLA-dependent
      interactions, leading to accelerated disease progression. To test this hypothesis
      we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men
      and 202 Rwandan heterosexual women followed up to 13 years from HIV-1
      seroconversion. We performed intermediate- and selective high-resolution
      molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA
      class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found
      at increasingly high frequency among individuals with successively more rapid
      progression to late-stage HIV-1-related conditions. In the combined cohorts (n =
      342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus
      slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p =
      0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous
      genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not
      exert any deleterious effect on HIV-1 disease progression. These findings suggest
      strongly that diversity in addition to sequence specificity at HLA-A and -B loci
      can influence the rate of disease progression following HIV-1 infection.

PMID- 10082115
TI  - HIV type 1 V3 domain serotyping and genotyping in Gauteng, Mpumalanga, KwaZulu
      Natal, and Western Cape Provinces of South Africa.
AB  - More than 20.8 million people are living with HIV/AIDS in sub-Saharan Africa,
      with southern Africa the worst affected area and accounting for one of the
      fastest growing AIDS epidemics worldwide. Samples from 81 patients, including 25
      from KwaZulu-Natal, 26 from Gauteng, 5 from Mpumalanga, and 25 from Western Cape
      Province, were serotyped using a competitive V3 peptide enzyme immunoassay
      (cPEIA). Viral RNA was also isolated from serum and the V3 region amplified by
      reverse transcriptase polymerase chain reaction (RT-PCR) to obtain a 240-bp
      product for direct sequencing of 29 samples. CLUSTAL W was used to make multiple
      sequence alignments. Distance calculation, tree construction methods, and
      bootstrap analysis were done using TREECON. Subtype C-like V3 loop sequences
      predominate in all provinces tested in South Africa. Discordant sero- and
      genotype results were observed in one patient only. The correlation between sero-
      and genotyping was 96% (24 of 25) in KwaZulu-Natal and 100% in Gauteng and
      Mpumalanga. In Western Cape Province 18% of patients were identified as
      sero/genotype B and 82% as sero/genotype C. Our data show that results of the
      second-generation V3 cPEIA correlated well with V3 sequencing and would be a
      rapid and affordable screening test to monitor the explosive southern African HIV
      1 epidemic.

PMID- 10082116
TI  - Genetic analysis of human immunodeficiency virus type 1 strains in Kenya: a
      comparison using phylogenetic analysis and a combinatorial melting assay.
AB  - We surveyed human immunodeficiency virus (HIV) subtype distribution from
      peripheral blood mononuclear cells (PBMCs) collected in 1995 from 24 HIV-1
      infected Kenyan residents (specimens from predominantly male truck drivers and
      female sex workers near Mombasa and Nairobi). Processed lysates from the PBMC
      samples were used for env amplification, directly sequenced, and analyzed by
      phylogenetic analysis. Envelope amplification products were also used for
      analysis in a polymerase chain reaction (PCR)-based assay, called the
      combinatorial melting assay (COMA). Results of the two tests were compared for
      assignment of subtype for this Kenyan cohort. The COMA, a PCR capture technique
      with colorimetric signal detection, was used with HIV reference subtype strains
      as well as regional (East Africa) HIV strains for subtype identification.
      Performance of the COMA was at 100% concordance (24 of 24) as compared with DNA
      sequencing analysis. Phylogenetic analysis showed 17 isolates to be subtype A, 3
      subtype D, and 4 subtype C viruses. This may represent an increase in subtype C
      presence in Kenya compared with previously documented reports. The COMA can offer
      advantages for rapid HIV-1 subtype screening of large populations, with the use
      of previously identified regional strains to enhance the identification of local
      strains. When more detailed genetic information is desired, DNA sequencing and
      analysis may be required.

PMID- 10082117
TI  - Frequency of a mutated CCR-5 allele (delta32) among Italian healthy donors and
      individuals at risk of parenteral HIV infection.
AB  - The aim of this study was to assess the frequency of a truncated allele of the
      CCR-5 gene (delta32) in Italy, and address its possible role in parenteral HIV
      transmission, as well as its influence in HIV-associated disease progression. In
      371 unrelated seronegative healthy blood donors the delta32 allele frequency was
      0.047; this figure was significantly different from those reported in northern
      America and northern Europe populations. However, delta32 allele frequency in
      healthy individuals did not differ significantly from that found in 54
      seronegative drug users (0.065), 98 seronegative hemophiliacs (0.051), and 81
      seropositive hemophiliacs (0.049). Although in seropositive hemophiliacs the
      wt/delta32 heterozygous genotype was associated with a trend to a slower decline
      in CD4+ cell counts, its presence did not seem to influence disease progression,
      as comparable delta32 allele frequency frequencies were found among progressing
      (0.042) and nonprogressing (0.111) patients. These data do not seem to support a
      protective role of the delta32 allele in preventing HIV infection through the
      parenteral route, or in influencing the natural history of the disease in this
      particular risk category, although the delta32 heterozygous state was associated
      with lower plasma viremia levels. On the other hand, the finding of non-syncytium
      inducing HIV strains in the majority of delta32 heterozygous seropositive
      patients suggests that its presence could not be a major factor in driving a
      switch toward more cytopathic, T-tropic HIV strains through selective pressure in
      coreceptor usage.

PMID- 10082118
TI  - Heterodimer-loaded erythrocytes as bioreactors for slow delivery of the antiviral
      drug azidothymidine and the antimycobacterial drug ethambutol.
AB  - Disseminated infection with Mycobacterium avium complex (MAC) remains the most
      common serious bacterial infection in patients with advanced AIDS. The organisms
      that make up this complex are found ubiquitously in the environment, yet rarely
      cause disseminated disease in nonimmunocompromised human patients; on the
      contrary, up to 50% of patients with AIDS may ultimately develop the pathology.
      Hence, therapeutic strategies able to inhibit HIV and Mycobacterium replication
      are needed. Because of the rapid plasma elimination and toxicity of the most
      commonly used drugs, daily multiple-drug therapies must often be continued
      throughout life, frequently causing major side effects and, as a consequence,
      poor patient compliance. Therefore, alternative strategies that reduce the
      toxicity of the drugs and allow prolonged application intervals are sorely
      needed. Since erythrocytes (RBCs) can behave as bioreactors able to convert
      impermeant prodrugs to membrane-releasable active drugs, new compounds (AZTpEMB,
      AZTpEMBpAZT, and AZTp2EMB) consisting of both an antiretroviral and an
      antimicrobial drug were designed and synthesized. Among these, only AZTp2EMB was
      hydrolyzed by erythrocyte enzymes and could be encapsulated inside RBCs. AZTp2EMB
      loaded RBCs slowly released AZT and EMB in culture medium, reducing its
      concentration by one-half about every 48 hr of incubation at 37 degrees C.
      Moreover, when AZTp2EMB-loaded erythrocytes were incubated for 6 days in the
      presence of human macrophages infected with Mycobacterium avium (M. avium) a
      marked bactericidal effect (>1 log) was observed. Thus, AZTp2EMB-loaded
      erythrocytes could be used as endogenous bioreactors for AZT and EMB delivery in
      the treatment of HIV and M. avium infection.

PMID- 10082119
TI  - The HIV type 1 protease inhibitor saquinavir can select for multiple mutations
      that confer increasing resistance.
AB  - Previous use of the HIV-1 protease inhibitor saquinavir resulted in the
      infrequent appearance of mutations in the HIV-1 protease gene associated with
      resistance. We have examined the ability of saquinavir to select for resistance
      mutations. In multiple selections of HIV-1 in cell culture with saquinavir,
      similar patterns of mutations were reproducibly observed and the number of
      mutations increased with increasing selective pressure. In a small number of
      subjects who showed an antiviral response when saquinavir was added to their
      therapeutic regimen, similar mutations were detected in viral genomic RNA in vivo
      after 30 to 40 weeks of therapy. These results indicate that saquinavir can
      select for resistance mutations and suggest that the infrequent appearance of
      these mutations in vivo is the result of low drug exposure. These results also
      predict that the use of higher levels of saquinavir will lead to an even greater
      frequency of resistance mutations in patients who fail therapy.

PMID- 10082120
TI  - The relative resistance of HIV type 1-infected chimpanzees to AIDS correlates
      with the maintenance of follicular architecture and the absence of infiltration
      by CD8+ cytotoxic T lymphocytes.
AB  - Lymphoid tissues are the focus of critical events in HIV pathogenesis. Persistent
      and high levels of virus production, extensive trapping of virus particles in
      germinal centers, and progressive degenerative changes in lymph node architecture
      are characteristics of progressive HIV-1 infection. Infiltrates of granzyme B-
      and TIA-expressing CD8+ "cytotoxic" T lymphocytes (CTLs) precede involution of
      germinal centers in humans who develop AIDS. Similar to humans, HIV-1 infection
      in chimpanzees is active and persistent. However, in contrast to humans, they
      remain relatively resistant to AIDS. Lymph node biopsies from chimpanzees
      infected with HIV-1 or a related chimpanzee lentivirus were studied for the level
      and pattern of virus expression, changes in lymphoid architecture, CD8+ T cell
      infiltrates and the presence or absence of CTL markers. In stark contrast to HIV
      1-infected humans, lymph nodes from infected chimpanzees had little virus
      deposition in germinal centers and a paucity of virus-expressing cells. Although
      some of the lymph nodes examined from infected animals had moderate follicular
      hyperplasia with infiltrating CD8+ T cells, none had evidence of follicular
      fragmentation. Most importantly, in marked contrast to infected humans, CD8+ T
      cells infiltrating the germinal center were negative for the CTL marker granzyme
      B. This evidence suggests that the infiltration of CD8+ CTLs into the germinal
      centers of lymph nodes may be a key determinant in AIDS pathogenesis.

PMID- 10082121
TI  - Identification of TAXREB107 as an erythropoietin early response gene.
AB  - The protooncogenes c-myc and c-myb are erythropoietin (Epo)-regulated early
      response genes. They appear to play distinct roles in the growth- and
      differentiation-inducing signals of the hormone. Using a subtractive
      hybridization strategy, we have identified the murine homolog of the TAX response
      element-binding protein TAXREB107 as an Epo early response gene in Rauscher
      murine erythroleukemia cells. This was confirmed by Northern blot analyses, which
      showed a fourfold increase in TAXREB107 mRNA after 1 hr of erythropoietin
      treatment. After 3 hr the transcript had decreased to approximately twofold above
      control levels. Inhibition of this induction with antisense oligodeoxynucleotides
      increased Epo-induced hemoglobinization 2.5-fold. The results implicate TAXREB107
      in erythropoiesis and support the hypothesis that the TAXREB proteins have
      functions outside the context of HTLV-I infection.

PMID- 10082122
TI  - The V3 loop-mimicking pseudopeptide 5[Kpsi(CH2N)PR]-TASP inhibits HIV infection
      in primary macrophage cultures.
AB  - The V3 loop-mimicking pseudopeptide 5[Kpsi(CH2N)PR]-TASP [psi(CH2N) representing
      a reduced peptide bond], which presents pentavalently the tripeptide
      Kpsi(CH2N)PR, is a potent inhibitor of HIV entry. By its capacity to bind
      specifically protein components on the cell surface, 5[Kpsi(CH2N)PR]-TASP blocks
      the attachment of virus particles to permissive CD4+ cells. Here, the inhibitory
      effect of 5[Kpsi(CH2N)PR]-TASP was investigated in monocyte-derived macrophages
      (MDMs) infected by the monocytotropic HIV-1(Ba-L) isolate. We show that
      5[Kpsi(CH2N)PR]-TASP inhibits HIV-1(Ba-L) infection in a dose-dependent manner,
      with more than 90% inhibition at 2 microM concentration. On the other hand, the
      control 5[QPQ]-TASP construct and the monovalent Kpsi(CH2N)PR tripeptide have no
      effect even at high concentrations. Under such experimental conditions, the
      biotin-labeled 5[Kpsi(CH2N)PR]-TASP, but not the Kpsi(CH2N)PR construct, binds
      specifically to the surface of MDMs and forms a stable complex with the cell
      surface-expressed nucleolin, as has been demonstrated to be the case in
      peripheral blood mononuclear cells. Infection of MDMs by HIV-1(Ba-L) could also
      be inhibited by beta-chemokines RANTES and MIP-1beta. Interestingly, association
      of low concentrations of 5[Kpsi(CH2N)PR]-TASP and beta-chemokines results in a
      synergistic inhibitory effect on HIV infection compared with the effect observed
      with each reagent alone. The inhibitory effect of 5[Kpsi(CH2N)PR]-TASP in primary
      macrophage cultures point out its potential as an anti-HIV drug in cells, which
      are the natural viral targets.

PMID- 10082123
TI  - Passively administered neutralizing serum that protected macaques against
      infection with parenterally inoculated pathogenic simian-human immunodeficiency
      virus failed to protect against mucosally inoculated virus.
AB  - Macaques inoculated orally, vaginally, or parenterally with SHIV(KU-1) develop
      severe systemic infection, acute loss of CD4+ T cells, and AIDS. We showed in a
      previous report that passive immunization with neutralizing serum protected
      macaques against infection with parenterally inoculated pathogenic SHIV given 24
      hr later. In the study reported here we asked whether the identical passive
      immunization protocol would protect macaques against infection with pathogenic
      SHIV following oral inoculation of the virus. Ten pigtail macaques were
      inoculated orally with one animal infectious dose of SHIV(KU-1). Four of the 10
      had been given pooled anti-SHIV plasma (15 ml/kg) 24 hr earlier, 4 others were
      given the same dose of anti-SHIV plasma 2 hr after virus challenge, and the 2
      remaining animals were used as controls. The neutralizing antibodies failed to
      protect macaques against infection after mucosal challenge with SHIV(KU-1).

PMID- 10082124
TI  - A predominantly HIV type 1 subtype C-restricted epidemic in South African urban
      populations.

PMID- 10082125
TI  - Phylogenetic examination of HIV type 1 glycoprotein 120-V3 sequences in patients
      from rural Georgia.

PMID- 10082126
TI  - Alpha-granule secretion from alpha-toxin permeabilized, MgATP-exposed platelets
      is induced independently by H+ and Ca2+.
AB  - In order to better understand granule release from platelets, we developed an
      alpha-toxin permeabilized platelet model to study alpha-granule secretion.
      Secretion of alpha-granules was analyzed by flow cytometry using P-selectin as a
      marker for alpha-granule release. P-selectin surface expression occurred when
      platelets were permeabilized in the presence of Ca2+. Responsiveness to Ca2+ was
      lost 30 min after permeabilization but could be reconstituted with MgATP. Alpha
      toxin-permeabilized, MgATP-exposed platelets also degranulated within a pH range
      of 5.4-5.9 without exposure to and independent of Ca2+. ATP, GTP, CTP, UTP, and
      ITP supported Ca2+-induced alpha-granule secretion, while H+-induced alpha
      granule secretion occurred only with ATP and GTP. Both Ca2+- and H+-induced alpha
      granule secretion required ATP hydrolysis. Kinase inhibitors blocked both Ca2+-
      and H+-induced secretion. These data suggest that alpha-granule secretion in this
      permeabilized platelet system shares many characteristics with granule secretion
      studied in other permeabilized cell models. Furthermore, these results show that
      H+ can trigger alpha-granule release independent of Ca2+.

PMID- 10082127
TI  - Effects of donor age on the expression of a marker of replicative senescence (EPC
      1) in human dermal fibroblasts.
AB  - EPC-1 (early population doubling level cDNA-1) is a quiescence-specific gene
      expressed at high levels by early passage WI-38 fibroblasts under conditions of
      either density-dependent growth arrest or serum deprivation. Late passage WI-38
      cells lose the ability to express EPC-1 under all conditions tested. The decline
      in EPC-1 mRNA is gradual during the replicative life span and correlates
      inversely with the population doubling level (PDL) of the cells. The objective of
      this study was to determine whether the decline in EPC-7 mRNA abundance observed
      during proliferative senescence also occurs in cultures derived from donors of
      different ages. To address this question, we examined the abundance of EPC-1 mRNA
      in 28 skin fibroblast lines established from healthy donors of different ages
      ranging from 12 fetal weeks to 94 years. EPC-1 expression was measured, under
      conditions of growth arrest, prior to the end of the replicative life span of the
      cultures. Despite some variability in steady-state transcript levels among the
      cell lines, EPC-1 expression was significantly lower in cells derived from the
      fetal donor group (12-20 gestational weeks) than in cells derived from adult
      donors. An in vitro age-dependent decline in EPC-1 expression was observed in all
      the skin lines examined, independent of donor age; however, no significant
      difference was observed between the young adult donor group (17-33 years) and the
      old adult donor group (78-94 years). Thus, expression of EPC-1 is linked to the
      replicative age of the cells and whether the cells are derived from fetal skin or
      adult skin. In adults, EPC-1 expression is independent of donor age.

PMID- 10082128
TI  - Identification of a heparin binding site and the biological activities of the
      laminin alpha1 chain carboxy-terminal globular domain.
AB  - The carboxy-terminal globular domain (G-domain) of the laminin alpha1 chain has
      been shown to promote heparin binding, cell adhesion, and neurite outgrowth. In
      this study, we defined the potential sequences originating from the G-domain of
      laminin alpha1 chain which possess these functional activities. A series of
      peptides were synthesized from the G-domain, termed LG peptides (LG-1 to LG-6)
      and were tested for their various biological activities. In the direct [3H]
      heparin binding assays, LG-6 (residues 2,335-2,348: KDFLSIELVRGRVK) mediated high
      levels of [3H]heparin binding, and this peptide also directly promoted cell
      adhesion and spreading, including B16F10, M2, HT1080, and PC12 cells. The peptide
      LG-6 also promoted the neurite outgrowth of PC12 cells, mouse granule cells, and
      chick telencephalic cells. An anti-peptide LG-6 antibody inhibited laminin-1 and
      peptide LG-6-mediated cell adhesion and neurite outgrowth. Furthermore, an anti
      integrin alpha2 antibody also inhibited the cell adhesion activity. These results
      suggest that peptide LG-6 plays a functional role as a heparin binding site in
      the G-domain of the laminin alpha1 chain, and this sequence was thus concluded to
      play a crucial role in regulating cell adhesion and spreading and neurite out
      growth which is related to integrin alpha2.

PMID- 10082129
TI  - Decreased expression and activity of the immediate-early growth response (Egr-1)
      gene product during cellular senescence.
AB  - Human diploid fibroblasts (HDFs) undergo a limited number of population doublings
      in culture before reaching the end of their proliferative life span, an event
      termed in vitro cellular senescence. Considerable evidence suggests that altered
      expression of key genes involved in the mitogenic response may be responsible for
      the inability of senescent cells to proliferate. Here we examined the expression
      and activity of the early growth response-1 (egr-1) gene, an "immediate-early"
      gene that is believed to link extracellular mitogenic signals to cell-cycle
      progression. We found that egr-1 was strongly downregulated in senescent HDFs at
      the level of mRNA, protein, and DNA binding activity. Decreased DNA binding
      activity of Egr-1 in vitro corresponded to decreased transcriptional activation
      in vivo. To further understand the mechanism of egr-1 downregulation, we examined
      the potential role of the serum response elements (SREs) present in the egr-1
      promoter. Electrophoretic mobility shift studies using young and old cell nuclear
      extracts showed a marked decrease in serum response factor (SRF) binding activity
      to the SRE in old compared to young cells. Loss of SRF binding activity has been
      correlated with the loss of expression of another growth-related immediate-early
      gene (c-fos). These results suggest a common mechanism for the downregulation of
      c-fos, egr-1, and other SRE-dependent, mitogen-responsive genes during cellular
      senescence.

PMID- 10082130
TI  - Possible involvement of p21 but not of p16 or p53 in keratinocyte senescence.
AB  - It has been reported that p21, p53, and p16 affect the cell cycle and cell
      senescence. However, their roles in keratinocyte senescence are not clear. We
      established primary keratinocyte strains from 15 donors and maintained them until
      replicative senescence; their population doublings ranged from 5.7-45.2. These
      strains were classified based on their population doublings as short (5.7-10.4),
      intermediate (13.9-17.4), and long (21.5-45.2). To investigate the roles of p21,
      p53, and p16 in the cellular senescence of the cultured keratinocytes, we
      quantitatively analyzed p21, p53, and p16 levels of keratinocyte strains with
      different life spans by Western blot with Fluorol mager. p21 levels increased in
      the senescent phase but not in the nonsenescent phase in all of the short,
      intermediate, and long life-span strains. Northern blot analysis also revealed
      induction of p21 mRNA was similar to that of p21 protein levels. There were no
      apparent differences in p53 levels between senescent and nonsenescent cells. The
      short life-span strains exhibited a significant increase in p16 levels in the
      senescent phase (eighth or tenth passage). However, in two long life-span
      strains, p16 levels were increased in the nonsenescent phase (eighth passage) but
      then declined as the cells reached senescence (twenty-seventh passage).
      Therefore, induction of p16 appeared not to be associated with senescence in long
      life-span strains. In conclusion, p21 but not p16 or p53 may play roles in
      keratinocyte senescence.

PMID- 10082131
TI  - Possible involvement of caspase-like family in maintenance of cytoskeleton
      integrity.
AB  - Caspases, a family of cysteine proteases, are the key effector proteins of
      apoptosis. These proteases cleave cellular proteins and are responsible for the
      destruction of the cell body during apoptosis. They are also involved in the
      activation of other proteins, such as cytokines. In this study, we demonstrate a
      novel function for these proteases. Z-Asp-CH2-DCB (Z-Asp), a general caspase
      inhibitor, blocked cell spreading on collagen-coated plates in a dose-dependent
      manner but did not affect cell viability. Caspase 3-like activity but not caspase
      1-like activity was detected in adherent cells on both collagen-coated and poly-L
      lysine-coated plates but not in suspended cells. The caspase 3-like activity was
      significantly inhibited by Z-Asp. However, only Z-Asp, not specific caspase
      inhibitors (Z-DEVD for caspase 3, Z-YVAD for caspase 1), was effective in the
      suppression of cell spreading. The inhibitory effect of Z-Asp was blocked by a
      phosphokinase C activator, PMA, and a Rho activator, lysophosphatidic acid (LPA),
      while neither a Rac activator, bradykinin, nor a Cdc42 activator, sphingosine-1 
      phosphate, was effective. Immunoprecipitation demonstrated that Z-Asp
      downregulated the expression of focal adhesion kinase (FAK) protein, downstream
      of Rho signaling, in adherent cells. Our results suggest that not caspase 1 or 3
      but another yet unknown caspase(s) plays an important role in the maintenance of
      cytoskeleton integrity via FAK protein expression, implying a new function for
      caspases.

PMID- 10082132
TI  - Transforming growth factor-alpha short-circuits downregulation of the epidermal
      growth factor receptor.
AB  - Transforming growth factor-alpha (TGFalpha) is an epidermal growth factor
      receptor (EGFR) ligand which is distinguished from EGF by its acid-labile
      structure and potent transforming function. We recently reported that TGFalpha
      induces less efficient EGFR heterodimerization and downregulation than does EGF
      (Gulliford et al., 1997, Oncogene, 15:2219-2223). Here we use isoform-specific
      EGFR and ErbB2 antibodies to show that the duration of EGFR signalling induced by
      a single TGFalpha exposure is less than that induced by equimolar EGF. The
      protein trafficking inhibitor brefeldin A (BFA) reduces the duration of EGF
      signalling to an extent similar to that seen with TGFalpha alone; the effects of
      TGFalpha and BFA on EGFR degradation are opposite, however, with TGFalpha sparing
      EGFR from downregulation but BFA accelerating EGF-dependent receptor loss. This
      suggests that BFA blocks EGFR recycling and thus shortens EGF-dependent receptor
      signalling, whereas TGFalpha shortens receptor signalling and thus blocks EGFR
      downregulation. Consistent with this, repeated application of TGFalpha is
      accompanied by prolonged EGFR expression and signalling, whereas similar
      application of EGF causes receptor downregulation and signal termination. These
      findings indicate that constitutive secretion of pH-labile TGFalpha may
      perpetuate EGFR signalling by permitting early oligomer dissociation and
      dephosphorylation within acidic endosomes, thereby extinguishing a
      phosphotyrosine-based downregulation signal and creating an irreversible
      autocrine growth loop.

PMID- 10082133
TI  - Tumor necrosis factor-alpha initiated signal transduction in 3T3-L1 adipocytes.
AB  - Examination of the ability of tumor necrosis factor-alpha (TNF) to activate both
      the p44/42 and p38 MAP kinase cascades in fully differentiated 3T3-L1 adipocytes
      indicated a rapid MEK1/2-dependent activation of p44/42 MAP kinase. Use of the
      MEK1/2 inhibitor PD98059 indicated that this pathway at least in part was
      responsible for nuclear localization of the transcription factor NF-kappaB. The
      stress/cytokine-activated p38 MAP kinase was observed to be constitutively
      active, and its phosphorylation (activation) status was not altered with TNF
      treatment. However, TNF treatment did result in activation of the transcription
      factor, ATF-2, a primary downstream target of p38 MAP kinase. Use of the p38 MAP
      kinase inhibitors SB202190 and SB203580 did not interfere with the ability of TNF
      to activate ATF-2, suggesting that either the gamma isoform of p38 MAP kinase or
      a p38-independent pathway was utilized by TNF to increase the phosphorylated
      fraction of ATF-2. In previous studies we had demonstrated the ability of TNF to
      suppress the transcription of the GLUT4 gene. Prevention of activation of either
      the p44/42 MAP kinase pathway (PD98059) or the p38 MAP kinase pathway (SB202190
      and SB202580) indicated that these pathways did not control GLUT4 transcription.

PMID- 10082134
TI  - Cobalt chloride-induced signaling in endothelium leading to the augmented
      adherence of sickle red blood cells and transendothelial migration of monocyte
      like HL-60 cells is blocked by PAF-receptor antagonist.
AB  - In response to hypoxia, sickle red blood cells (SS RBC) and leukocytes exhibit
      increased adherence to the vascular endothelium, while diapedesis of leukocytes
      through the blood vessel increases. However, the cellular signaling pathway(s)
      caused by hypoxia is poorly understood. We utilized CoCl2 as a mimetic molecule
      for hypoxia to study cellular signaling pathways. We found that in human
      umbilical vein endothelial cells (HUVEC), CoCl2 at 2 mM concentration induced the
      surface expression of a subset of CAMs (VCAM-1) and activation of transcription
      factor NF-kappaB in the nuclear extracts of HUVEC. Furthermore, CoCl2 also caused
      time-dependent tyrosine phosphorylation of mitogen-activated protein (MAP) kinase
      isoform ERK2 without significantly affecting ERK1, indicating ERK2 is the
      preferred substrate for upstream kinase of the MAPK pathway. Inhibitors of MAP
      kinase (PD98059) or platelet-activating factor (PAF)- receptor antagonist
      (CV3988) inhibited the CoCl2-induced NF-kappaB activation and VCAM-1 expression.
      Augmented expression of VCAM-1 led to increased SS RBC adhesion, inhibitable by a
      VCAM-1 antibody. Additionally, CoCl2 caused a two- to threefold increase in the
      rate of transendothelial migration of monocyte-like HL-60 cells and a twentyfold
      increase in phosphorylation of platelet endothelial cell adhesion molecules
      (PECAM-1). The transendothelial migration of monocytes was inhibited by an
      antibody to PECAM-1. Both phosphorylation of PECAM-1 and transendothelial
      migration of monocytes in response to CoCl2 were inhibited by protein kinase
      inhibitor (GF109203X) and augmented by protein phosphatase inhibitor (Calyculin
      A). Our data suggests that CoCl2-induced cellular signals directing increased
      expression of VCAM-1 in HUVEC involve downstream activation of MAP kinase and NF
      kappaB, while the phosphorylation of PECAM-1 occurs as a result of activation of
      PKC. We conclude that PAF-receptor antagonist inhibits the CoCl2- or hypoxia
      induced increase in the adhesion of SS RBC, PECAM-1 phosphorylation, and the
      concomitant transendothelial migration of monocytes.

PMID- 10082135
TI  - Tumor necrosis factor-alpha and CD95 ligation suppress erythropoiesis in Fanconi
      anemia C gene knockout mice.
AB  - Fanconi anemia (FA) is a genetic syndrome predisposing to hematopoietic failure.
      Little is known about the pathophysiology of FA, except that tumor necrosis
      factor-alpha (TNF-alpha) is overexpressed in patients. FA group C (Fac) gene
      knockout mice have been developed in order to model the human disease, but the
      mice do not spontaneously exhibit aplasia. To investigate secondary influences on
      hematopoiesis in the Fac-null mice, we studied the sensitivity of hematopoietic
      progenitor cells (HPC) to death receptor triggering by TNF-alpha and Fas receptor
      (CD95) ligation. Previously we had found that overexpression of a human FAC
      transgene protects hematopoietic progenitors from Fas-mediated apoptosis (Wang et
      al., 1998, Cancer Res 58:3538-3541). In the present experiments with Fac-null
      mice, growth of erythroid burst-forming units (BFU-E) was significantly inhibited
      by TNF-alpha and CD95 ligation. Flow cytometric analysis revealed that CD95 was
      induced more readily in the Fac-null CD34+ cell fraction. Apoptosis induced by
      TNF-alpha alone or with CD95 ligation also occurred more frequently in null mouse
      HPC. We then bred null mice against transgenic mice overexpressing TNF-alpha (at
      serum levels in the range of 100 pg/ml). Resultant Fac-null mice that
      overexpressed TNF-alpha not only yielded decreased numbers of BFU-E but also
      expressed higher levels of CD95 in the CD34+ fraction. We conclude that mutation
      in the Fac protein induces heightened sensitivity to TNF-alpha and Fas receptor
      ligation, results that may explain the mechanism of anemia in FA-C patients.

PMID- 10082136
TI  - Mitogen-activated protein kinase and phosphorylation of connexin43 are not
      sufficient for the disruption of gap junctional communication by platelet-derived
      growth factor and tetradecanoylphorbol acetate.
AB  - Disruption of gap junctional communication (GJC) by various compounds, including
      growth factors and tumor promoters, is believed to be modulated by the
      phosphorylation of a gap junctional protein, connexin43 (Cx43). We have
      previously demonstrated a platelet-derived growth factor (PDGF)-induced blockade
      of GJC and phosphorylation of Cx43 in T51B rat liver epithelial cells expressing
      wild-type PDGF receptor beta (PDGFr beta). Both of these actions of PDGF required
      participation of protein kinase C (PKC) and mitogen-activated protein kinase
      (MAPK). Similar requirements of MAPK were suggested in the modulation of GJC by
      other agents, including epidermal growth factor (EGF) and lysophosphatidic acid
      (LPA). Since many of these agents activate additional protein kinases, our
      present study examined whether activation of MAPK was sufficient for Cx43
      phosphorylation and GJC blockade. By utilizing a variety of MAPK activators, we
      now show that activation of MAPK is not always associated with either Cx43
      phosphorylation or disruption of GJC, which suggests a requirement for additional
      factors. Furthermore, pretreatment with hydrogen peroxide (H2O2), a potent MAPK
      activator but inefficient GJC/Cx43 modulator, abrogated PDGF- or TPA-induced
      disruption of GJC. While a 5 min H2O2 pretreatment abolished both PDGF- and TPA
      induced Cx43 phosphorylation and GJC blockade, a simultaneous H2O2 treatment
      interfered only with GJC closure but not with the phosphorylation of Cx43 induced
      by PDGF and TPA. This finding indicates that, in addition to the Cx43
      phosphorylation step, inhibition of GJC requires interaction with other
      components. H2O2-mediated abrogation of PDGF/TPA signaling can be neutralized by
      the antioxidant N-acetylcysteine (NAC) or by the tyrosine kinase inhibitor
      genistein. Taken together, our results suggest that disruption of GJC is not
      solely mediated by either activated MAPK or Cx43 phosphorylation but requires the
      participation of additional kinases and regulatory components. This complex mode
      of regulation is perhaps essential for the proposed functional role of GJC.

PMID- 10082137
TI  - Negative modulation of alpha1(I) procollagen gene expression in human skin
      fibroblasts: transcriptional inhibition by interferon-gamma.
AB  - Interferon-gamma (IFN-gamma), a multifunctional cytokine produced by activated
      Th1 lymphocytes, exerts potent effects on the extracellular matrix by regulating
      fibroblast function. In this study, we examined the modulation of alpha1(I)
      procollagen gene (COL1A1) expression by recombinant IFN-gamma. The results showed
      that IFN-gamma stimulated the rapid accumulation of interferon regulated factor
      (IRF)-1 mRNA, followed by a delayed and dose-dependent inhibition of alpha1(I)
      procollagen mRNA expression in skin fibroblasts from several different donors.
      The inhibitory response was abrogated in fibroblasts stably expressing IRF-1 in
      the antisense orientation. A marked decrease in the amount of heterogeneous
      nuclear pre-mRNA preceded the inhibition of COL1A1 mRNA expression. In
      fibroblasts transiently transfected with COL1A1 promoter-chloramphenicol
      acetyltransferase reporter gene plasmids, IFN-gamma selectively inhibited
      promoter activity and abrogated its stimulation induced by TGF-beta. The
      inhibition by IFN-gamma was not due to downregulation of TGF-beta receptor mRNA
      expression in the fibroblasts or decreased ligand binding to the receptor. IFN
      alpha and IFN-beta by themselves had little effect on promoter activity, but IFN
      alpha augmented the inhibitory effect of IFN-gamma. Using a series of 5' deletion
      constructs, a proximal region of the COL1A1 promoter was shown to function as an
      IFN-gamma response element. This region of the gene harbors overlapping binding
      sites for transcription factors Sp1, Sp3, and NF-1 but no homologs of previously
      characterized IFN-gamma response elements. The putative IFN-gamma response region
      was sufficient to confer inhibition of reporter gene expression by treatment with
      IFN-gamma. Gel mobility shift analysis showed that two distinct and specific DNA
      protein complexes were formed when fibroblast nuclear extracts were incubated
      with oligonucleotides spanning the IFN-gamma response region. IFN-gamma did not
      modify the ability of nuclear proteins to bind to this region. The results
      indicate that IFN-gamma inhibits COL1A1 expression in fibroblasts principally at
      the level of gene transcription. Inhibition involves IRF-1 and is mediated
      through a short proximal promoter segment but without an apparent change in
      promoter occupancy. The findings provide novel insight into the mechanism of IFN
      gamma regulation of fibroblast function.

PMID- 10082138
TI  - Cell-type-specific activation of c-Jun N-terminal kinase by salicylates.
AB  - Salicylates inhibit signaling by tumor necrosis factor (TNF), including TNF
      induced activation of mitogen-activated protein kinases (MAPKs). On the other
      hand, we recently showed that in normal human diploid fibroblasts sodium
      salicylate (NaSal) elicits activation of p38 MAPK but not activation of c-Jun N
      terminal kinase (JNK). Here we show that NaSal treatment of COS-1 or HT-29 cells
      produced a sustained c-Jun N-terminal kinase (JNK) activation. Activation of JNK
      or p38 MAPK by NaSal (or aspirin) was not due to a nonspecific hyperosmotic
      effect because much higher molar concentrations of sorbitol or NaCl were required
      to produce a similar activation. Three structurally unrelated nonsteroidal
      antiinflammatory drugs (ibuprofen, acetaminophen, and indomethacin) failed to
      induce significant activation of JNK or p38 MAPK, suggesting that cyclooxygenase
      inhibition is not the underlying mechanism whereby salicylates induce p38 MAPK
      and JNK activation. Activation of JNK and p38 MAPKs may be relevant for some
      antiinflammatory actions of salicylates.

PMID- 10082139
TI  - Calculating the global burden of disease: time for a strategic reappraisal?

PMID- 10082140
TI  - It'll only hurt a second? Microeconomic determinants of who gets flu shots.
AB  - Appreciating how the propensity to be immunized against the flu depends on
      individual characteristics and environments is essential for policies regarding
      influenza control to be formulated sensibly. To this point, the literature has
      offered little documentation on the determinants of influenza immunization.
      Beyond epidemiology, there are important economic issues that must be addressed
      to understand this form of preventive care. One concerns the relationship between
      labour supply and immunization propensity: While it is relatively costly (in
      terms of time costs) for workers to obtain immunizations, workers also have
      relatively more to lose from being ill with the flu. Another concern not
      generally appreciated is the extent to which individuals' perceived risks of
      infection may affect their propensities to be immunized. The paper also attempts
      to shed light on these issues. The analysis uses data from the 1991 National
      Health Interview Survey. Immunization propensity displays expected patterns by
      age and health status, while the results with respect to race, household
      structure, income and insurance are somewhat more surprising and/or novel. The
      estimated labour supply and perceived risk effects suggest that some aspects of
      the economics of preventive care generally not considered in empirical work are
      important and merit further consideration.

PMID- 10082141
TI  - Incorporating societal concerns for fairness in numerical valuations of health
      programmes.
AB  - The paper addresses some limitations of the QALY approach and outlines a
      valuation procedure that may overcome these limitations. In particular, we focus
      on the following issues: the distinction between assessing individual utility and
      assessing societal value of health care; the need to incorporate concerns for
      severity of illness as an independent factor in a numerical model of societal
      valuations of health outcomes; similarly, the need to incorporate reluctance to
      discriminate against patients that happen to have lesser potentials for health
      than others; and finally, the need to combine measurements of health-related
      quality of life obtained from actual patients (or former patients) with
      measurements of distributive preferences in the general population when
      estimating societal value. We show how equity weights may serve to incorporate
      concerns for severity and potentials for health in QALY calculations. We also
      suggest that for chronically ill or disabled people a life year gained should
      count as one and no less than one as long as the year is considered preferable to
      being dead by the person concerned. We call our approach 'cost-value analysis'.

PMID- 10082142
TI  - A checklist for judging preference-based measures of health related quality of
      life: learning from psychometrics.
AB  - There have been a number of published reviews of measures of health related
      quality of life, but most of this work has been undertaken within a tradition of
      psychometrics outside of economics. This situation has often resulted in health
      status measures designed specifically for the purposes of economic evaluation
      being neglected and portrayed as 'invalid'. This paper utilizes and adapts the
      traditional psychometric concepts of practicality, reliability and validity for
      judging preference-based measures of health related quality of life. The
      psychometric and economic approaches are most different in relation to validity
      because they are seeking to measure different concepts. The former seeks to
      measure health change as perceived by patients, whilst economic evaluation
      requires a measure of the value or strength of preference for the health change.
      A checklist is presented to provide guidance in the design or review of economic
      evaluations using changes in health as the main measure of benefit.

PMID- 10082143
TI  - The economic consequences of reorganizing hospital services in Bishkek,
      Kyrgyzstan.
AB  - Kyrgyzstan gained independence from the Soviet Union in 1991 and has since been
      thrown into severe financial crisis. All public sector funding has been
      significantly reduced and international aid agencies are supporting the
      government in rebuilding the economy. The health sector requires a radical
      overhaul and a major part of this process involves rationalization of existing
      facilities, particularly in the capital Bishkek, where 26 secondary and tertiary
      hospitals support a population of approximately 800000 people. This paper
      describes the development of a plan for rationalization with particular emphasis
      on the economic aspects of the process. This involved calculating future hospital
      requirements by modelling a variety of policy options, ranging from changes to
      clinical practice to hospital closures. The model generates estimates of resource
      requirements at each hospital, from which the costs falling on the health budget
      and patients are derived.

PMID- 10082144
TI  - Priority care for employees: a blessing in disguise?
AB  - This paper discusses the efficiency and equity effects of priority care for
      employees. Recent privatization of workers' compensation insurance in the
      Netherlands caused an increasing tension between public responsibility for health
      care cost-containment and private responsibility for sick pay. As a result of
      strict supply side regulation, waiting lists increased, while at the same time
      employers became fully responsible for sick pay. To reduce sick pay and
      production losses, employers are prepared to pay for priority care by using
      available excess capacity. We argue that the criteria of Pareto and Rawls can
      provide a rationale for the resulting differential treatment of employees and non
      employees. However, such a justification crucially depends on weights society
      assigns to absolute versus relative improvements in access to health care.

PMID- 10082145
TI  - Response-ordering effects: a methodological issue in conjoint analysis.
AB  - Conjoint analysis is a technique relatively new to the evaluation of health care
      services in the UK. The technique uses data generated from questionnaires. This
      paper addresses the issue of response-ordering effects that may result from the
      ordering of dimensions of benefit within a question. Two questionnaires were
      given to 216 hospital consultants as part of a priority setting exercise. These
      were identical other than the ordering of the dimensions within each question.
      The regression analysis was segmented according to questionnaire type and the
      coefficients of the segmentation were tested for statistically significant
      differences. The results show no evidence of ordering effects.

PMID- 10082146
TI  - The continuum-of-addiction: cigarette smoking in relation to price among
      Americans aged 15-29.
AB  - We studied the relationship between current cigarette smoking and price among
      34145 respondents, aged 15-29 years, to the 1992-1993 Tobacco Use Supplements to
      the Current Population Survey. The price elasticity of current smoking varied
      inversely with age: -0.831 (S.E. 0.402) for ages 15-17; -0.524 (S.E. 0.256) for
      ages 18-20; -0.370 (S.E. 0.188) for ages 21-23; -0.202 (S.E. 0.175) for ages 24
      26; and -0.095 (S.E. 0.157) for ages 27-29. In response to higher prices, older
      youth were more likely to reduce the number of cigarettes smoked per day than to
      quit entirely. Among 15-17-year-olds, smoking cigarettes 'some days' was more
      sensitive to price than smoking 'every day'. Cigarette smoking was inversely
      related to the prices of premium brands, but not discount brands.

PMID- 10082147
TI  - The warm-up phenomenon and ischaemic preconditioning: an uncertain relationship.

PMID- 10082148
TI  - Pacing in hypertrophic cardiomyopathy.

PMID- 10082149
TI  - Perivalvular abscesses in infective endocarditis.

PMID- 10082150
TI  - The signal averaged P wave--out of the back room?

PMID- 10082151
TI  - Genetic and molecular basis of cardiac arrhythmias; impact on clinical
      management. Study group on molecular basis of arrhythmias of the working group on
      arrhythmias of the european society of cardiology.

PMID- 10082152
TI  - Effects of K(ATP) channel blockade by glibenclamide on the warm-up phenomenon.
AB  - AIMS: The increased tolerance to myocardial ischaemia observed during the second
      of two sequential exercise tests, i.e. the warm-up phenomenon, has been proposed
      as a clinical model of ischaemic preconditioning. As ATP-sensitive K+ channels
      appear to be a mediator of ischaemic preconditioning in both experimental and
      clinical studies, the aim of this study was to investigate the role of K(ATP)
      channels in the warm-up phenomenon. METHODS AND RESULTS: Twenty-six patients with
      coronary artery disease were randomized to receive 10 mg oral glibenclamide, a
      selective ATP-sensitive K+ channel blocker, or placebo. Sixty minutes after
      glibenclamide or placebo administration, patients were given an infusion of 10%
      dextrose (8 ml x min(-1)) to correct glucose plasma levels or, respectively, an
      infusion of saline at the same infusion rate. Thirty minutes after the beginning
      of the infusions, both patient groups underwent two consecutive treadmill
      exercise tests, with a recovery period of 15 min to re-establish baseline
      conditions. Before exercise tests, blood glucose levels were similar in placebo
      and glibenclamide groups (96 +/- 10 vs 105 +/- 22 mg x 100 ml(-1), P=ns). After
      placebo administration, rate-pressure product at 1.5 mm ST-segment depression
      significantly increased during the second exercise test compared to the first
      (220 +/- 41 vs 186 +/- 29 beats x min(-1) x mmHg x 10(2), P<0.01), but it did not
      change after glibenclamide (191 +/- 34 vs 187 +/- 42 beats x min(-1) x mmHg x
      10(2), P=ns), with a significant drug-test interaction (P=0.0091, at two-way
      ANOVA). CONCLUSIONS: Glibenclamide, at a dose previously shown to abolish
      ischaemic preconditioning during coronary angioplasty, prevents the increase of
      ischaemic threshold observed during the second of two sequential exercise tests.
      These findings confirm that ischaemic preconditioning plays a key role in the
      warm-up phenomenon and that in this setting is, at least partially, mediated by
      activation of ATP-sensitive K+ channels.

PMID- 10082153
TI  - Effects of permanent dual-chamber pacing on mitral regurgitation in hypertrophic
      obstructive cardiomyopathy.
AB  - AIMS: To assess the effects of chronic dual-chamber pacing on mitral
      regurgitation in hypertrophic obstructive cardiomyopathy. METHODS AND RESULTS:
      Twenty-three patients with hypertrophic obstructive cardiomyopathy and mitral
      regurgitation. treated with DDD pacing for 16 +/- 14 months, were included in the
      study. Mitral regurgitation was assessed by Doppler-echocardiography using semi
      quantitative analysis (grades I-IV) and by measuring the maximum regurgitant jet
      area/left atrial area ratio. At the end of follow-up, DDD pacing reduced the
      outflow gradient from 93 +/- 37 mmHg to 31 +/- 30 mmHg (P<0.0001). Nine of the 14
      patients who initially had > or =grade II mitral regurgitation improved by at
      least one grade, two of them exhibiting dramatic improvement (from grade IV and
      III to grade I). The regurgitant jet area/left atrial area ratio was reduced with
      DDD pacing from 20 +/- 13% to 11 +/- 6% (P<0.0001). Patients who had significant
      mitral regurgitation despite pacing were those whose outflow gradient remained
      high or those with mitral valve organic abnormalities (mitral annulus
      calcification or mitral valve prolapse). In the absence of organic abnormalities
      other than leaflet elongation, there was a significant correlation between the
      gradient value achieved with DDD pacing and the extent of mitral regurgitation
      (P<0.05). CONCLUSION: In the absence of organic mitral valve abnormalities, DDD
      pacing reduces in parallel mitral regurgitation and left ventricular outflow
      gradient. In such patients therefore, significant mitral regurgitation is not a
      contraindication to pacing.

PMID- 10082154
TI  - Dispersion of signal-averaged P wave duration on precordial body surface in
      patients with paroxysmal atrial fibrillation.
AB  - AIMS: This study sought to investigate whether the spatial dispersion of signal
      averaged P wave duration would be increased in patients with paroxysmal atrial
      fibrillation, by use of precordial mapping of the P wave signal-averaged ECG.
      METHODS AND RESULTS: The P wave signal-averaged ECG was recorded by the P wave
      triggering method from 16 precordial leads in 55 patients with paroxysmal atrial
      fibrillation and 57 control subjects. As an index of the dispersion of signal
      averaged P wave duration, we obtained the difference between the maximum and
      minimum in 16 recording sites. The dispersion was significantly greater in the
      patients with paroxysmal atrial fibrillation than the controls (26.6 +/- 9.5 vs
      14.8 +/- 6.7 ms, P<0.0001). In 25 patients with symptomatic attacks of paroxysmal
      atrial fibrillation, the signal-averaged ECG was repeated 1 h after a single dose
      of orally administered pilsicainide, a new class Ic drug. These patients were
      prospectively followed-up for 10 +/- 11 months with pilsicainide. The rate of
      freedom from recurrence of paroxysmal atrial fibrillation attacks was
      significantly (P<0.0001) higher in patients with whom dispersion was decreased by
      the single dose (54%[7/13]) than in those in whom dispersion increased
      (8%[1/12]). CONCLUSION: Increased dispersion of signal-averaged P wave duration
      would play an important role in generating paroxysmal atrial fibrillation and
      would be useful in the prediction of drug efficacy to evaluate the change in
      dispersion by a single administration of pilsicainide.

PMID- 10082155
TI  - Echocardiographic and morphological correlations in tetralogy of Fallot.
AB  - AIMS: Our aim was to clarify the location and structure of the outlet septum
      relative to the free-standing subpulmonary infundibulum in the setting of
      tetralogy of Fallot and to examine its relationship to the other components of
      the subpulmonary outflow tract, determining their potential influence on clinical
      outcome. METHODS AND RESULTS: We studied prospectively 41 patients with tetralogy
      of Fallot (mean age 14 +/- 10.9 months) prior to surgical repair, and compared
      them with 15 patients undergoing closure of a ventricular septal defect
      associated with malalignment of the outlet septum but no subpulmonary
      infundibular stenosis (Eisenmenger ventricular septal defect), and 20 healthy
      controls. We also examined available autopsied hearts from cases with uncorrected
      tetralogy of Fallot (8) and Eisenmenger ventricular septal defect (13). Data were
      indexed for body surface area, and diameter of the tricuspid valve, respectively.
      The overall length of the subpulmonary infundibulum, including the extent of the
      muscular outlet septum, was significantly greater for patients with tetralogy of
      Fallot compared to normals (2.34 +/- 0.6 vs 1.46 +/- 0.34 cm/BSA0.5, P<0.001),
      whereas the difference between those with tetralogy of Fallot and an Eisenmenger
      ventricular septal defect was confined to the degree of narrowing of the
      subpulmonary outlet (0.43 +/- 0.22 vs 2.17 +/- 0.64 cm/BSA0.5, P<0.001). Within
      the tetralogy of Fallot group, there were linear relationships between deviation
      of the outlet septum (r= -0.61, P<0.005) and the diameter of the pulmonary valvar
      orifice (r=0.75, P<0.001), suggesting that growth of the pulmonary arteries may
      be related to this feature. When patients requiring a transannular patch as part
      of their surgical repair were compared with those not needing this procedure,
      differences were found in the diameter of the pulmonary valvar orifice and the
      pulmonary trunk, but not in the dimensions of the outlet septum. CONCLUSION: The
      position of the outlet septum in relationship to the remainder of the muscular
      subpulmonary infundibulum represents a hallmark of tetralogy of Fallot,
      permitting its differentiation from Eisenmenger ventricular septal defects and
      normal hearts.

PMID- 10082156
TI  - Perivalvular abscesses associated with endocarditis; clinical features and
      prognostic factors of overall survival in a series of 233 cases. Perivalvular
      Abscesses French Multicentre Study.
AB  - AIMS: The purposes of this study were to determine the clinical features and to
      identify prognostic factors of abscesses associated with infective endocarditis.
      METHODS AND RESULTS: During a 5-year period from January 1989, 233 patients with
      perivalvular abscesses associated with infective endocarditis were enrolled in a
      retrospective multicentre study. Of the patients, 213 received medical surgical
      therapy and 20 medical therapy alone. No causative microorganism could be
      identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and
      80%, respectively using transthoracic and transoesophageal echocardiography.
      Surgical treatment consisted of primary suture of the abscess (38%), insertion of
      a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of
      the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial
      rates for overall survival at 3 and 27 months in operated patients were 75 +/-
      10% and 59 +/- 11%, respectively. Increasing patient age, staphylococcal
      infection, and fistulization of the abscess were found to be independent risk
      factors in both 1 month and overall operative mortality. Renal failure was a risk
      factor predictive of operative mortality at 1 month, whereas uncontrolled
      infection and circumferential abscess were regarded as risk factors predictive of
      overall operative mortality. CONCLUSION: The data determined prognostic factors
      of abscesses associated with infective endocarditis.

PMID- 10082157
TI  - Why growth hormone therapy is efficient in heart failure?

PMID- 10082158
TI  - Growth hormone in dilated cardiomyopathy (advantages and disadvantages)

PMID- 10082159
TI  - Tests for detection of snake venoms, toxins and venom antibodies: review on
      recent trends (1987-1997).
AB  - Various methods developed for the detection of snake venoms, toxins and venom
      antibodies, during the last decade is reviewed. Radioimmunoassay, agglutination
      assay, enzyme-linked immunosorbent assay (ELISA), fluorescence immunoassay etc.
      have been used for detection of venoms and toxins. Important contributions have
      been made to improve the specificity, sensitivity, rapidity and simplicity of the
      ELISA method. Monoclonal antibodies and affinity-purified venom-specific
      antibodies were used to achieve species specificity of ELISA and the latter seems
      to be the ideal for venom detection. Incorporation of avidin-biotin system as
      well as the fluorogenic substrate in the enzyme immunoassay sufficiently
      increased the sensitivity of the assay to detect venom concentrations to picogram
      levels. The ability to use undiluted blood and other whole biological fluids
      reduce the assay time considerably. Although there have been several reports were
      on venom detection, so far only a few field kits have been developed. This
      implies that the experiments and design were only at the laboratory levels and
      still more work has to be carried out before it could be used in the field.
      Concerning the venom antibody detection, ELISA has been used extensively and the
      humoral response of patients envenomed by snake has been investigated in detail.
      Non-specific reactivity along with cross-reactivity still limits the use of ELISA
      for species identification in epidemiological studies. Overall, ELISA remains the
      suitable method for the detection of snake venoms, toxins and venom antibodies in
      body fluids. The possible use of a biosensor approach to solve some of the
      problems associated with the ELISA method are also discussed.

PMID- 10082160
TI  - Oligosaccharide residues of Loxosceles intermedia (brown spider) venom proteins:
      dependence on glycosylation for dermonecrotic activity.
AB  - Loxosceles spp. (brown spider) envenomation has been reported to provoke
      dermonecrosis and haemorrhage at the bite site (a hallmark of accidents) and, to
      a lesser extent, thrombocytopenia, hemolysis and disseminated intravascular
      coagulation in some cases. Using lectin-immunolabeling, lectin-affinity
      chromatography, glycosidase and proteinase K treatments we were able to identify
      several venom N-glycosylated proteins with high-mannose oligosaccharide
      structures, complex-type glycoconjugates such as fucosylated glycans, but no
      galactose or sialic acid residues as complex sugars or glycosaminoglycan
      residues. Working with enzymatically or chemically deglycosylated venom we found
      that platelet aggregation (thrombocytopenic activity) as well as the
      fibronectinolytic and fibrinogenolytic (haemorrhagic) effects of the venom were
      sugar-independent when compared to glycosylated venom. Nevertheless, zymograph
      analysis in co-polymerized gelatin gels showed that enzymatic N-deglycosylation
      of loxolysin-B, a high-mannose 32-35 kDa glycoprotein of the venom with
      gelatinolytic metalloproteinase activity, caused a reduction of approximately 2
      kDa in its molecular weight and a reduction of the gelatinolytic effect to a
      residual activity of 28% when compared to the glycosylated molecule, indicating a
      post-translational glycosylation-dependent gelatinolytic effect. Analysis of the
      dermonecrotic effect of the chemically or enzymatically N-deglycosylated venom
      detected only residual activity when compared with the glycosylated control.
      Thus, the present report suggests that oligosaccharide moieties play a role in
      the destructive effects of brown spider venom and opens the possibility for a
      carbohydrate-based therapy.

PMID- 10082161
TI  - Primary structure of gamma-bungarotoxin, a new postsynaptic neurotoxin from venom
      of Bungarus multicinctus.
AB  - The primary structure of gamma-bungarotoxin, a new toxin from Bungarus
      multicinctus venom, was determined using mass spectrometry and Edman degradation.
      The toxin has a mass of 7524.7 D and consists of 68 residues having the following
      sequence: MQCKTCSFYT CPNSETCPDG KNICVKRSWT AVRGDGPKRE IRRECAATCP PSKLGLTVFC
      CTTDNCNH. Gamma-bungarotoxin is structurally similar to both kappa-bungarotoxin
      and elapid long postsynaptic neurotoxins. Its C-terminal nine residues are
      identical to those of the kappa-toxins. Its disulfide bond locations appear
      identical to those of several elapid toxins of unknown pharmacology and its
      hydrophobicity profile is also strikingly similar. However, with an LD50 of 0.15
      microg/g i.v. in mice, gamma-bungarotoxin is 30-150-fold more toxic than other
      members of this latter class. Its toxicity is comparable to those of alpha
      nicotinic acetylcholine receptor antagonists.

PMID- 10082162
TI  - Ontogenetic development of Loxosceles intermedia spider venom.
AB  - Envenomation by Loxosceles spider has become a public health problem in the South
      region of Brazil, mainly due to high levels of domiciliary infestation by
      Loxosceles intermedia spiders. The toxic effects of L. intermedia venom are
      mostly associated with a 35 kDa protein (F35) which presents complement-dependent
      haemolytic and dermonecrotic activities. The aim of this study was to detect,
      through biological and immunochemical assays, the appearance of the main toxic
      component, F35, during the ontogenetic development of L. intermedia spiders. The
      toxin appeared in its fully active form in venom of third instar spiderlings;
      from then on its activity increased throughout development until adulthood. On
      the other hand, F35 was not detected in extracts of either eggs or spiderlings of
      the first and second instars.

PMID- 10082163
TI  - Neutralization of edema, hemorrhage and myonecrosis induced by North American
      crotalid venoms in simulated first-aid treatments.
AB  - Venoms of the broad-banded copperhead (Agkistrodon contortrix laticinctus, ACL)
      and the prairie rattlesnake (Crotalus viridis viridis, CVV), like other crotalid
      venoms, cause severe local tissue damage such as edema, hemorrhage and
      myonecrosis. Antivenom therapy is not very effective in neutralizing this local
      tissue damage, and such observations support the need for an effective first-aid
      regimen aimed at minimizing local tissue reactions. Some of the local tissue
      damage induced by these venoms is due to phospholipase A2 myotoxins, and since
      para-bromophenacyl bromide (p-BPB), an inhibitor of PLA2 catalytic activity, has
      been shown to inhibit the myotoxic action of two PLA2 myotoxins, we hypothesized
      that this compound would inhibit part of the myotoxic activity of these crude
      venoms. For in vitro neutralization experiments, venoms were mixed with
      combinations of either p-BPB, antivenom or both prior to injection into the
      muscles of the lower hindlimb of mice. For in vivo neutralization experiments,
      mice were injected with venom followed by either topical DMSO containing p-BPB or
      intramuscular injection with saline containing p-BPB. A final set of mice
      received these same injections followed by i.p. infusions of antivenom to
      simulate experimental first-aid followed by hospital treatment. In the in vitro
      neutralization tests, edema was significantly reduced when both antagonists were
      used together, and there was a highly significant neutralization of ACL- and CVV
      generated myonecrosis. In the in vivo neutralization experiments, hemorrhage was
      significantly reduced when injection of ACL venom was followed by topical DMSO-p
      BPB, and myonecrosis was reduced when injection of ACL venom was followed by
      intramuscular injection of saline-p-BPB. Antivenom significantly reduced edema,
      hemorrhage and myonecrosis induced by CVV venom, but reduced only myonecrosis
      induced by ACL venom. Taken together, these results suggest a role for pBPB in
      the first-aid treatment of snakebite especially when followed by hospital
      treatment with antivenom.

PMID- 10082164
TI  - TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus
      venom which acts on Ca2+-activated K+ channels.
AB  - The primary structure of TsTX-IV, a neurotoxin isolated from Tityrus serrulatus
      scorpion venom, is reported. Its amino acid sequence was determined by automated
      Edman sequential degradation of the reduced and carboxymethylated toxin and of
      relevant peptides obtained by digestion with Staphylococcus aureus strain V8
      protease or trypsin and cleavage by CNBr. The complete sequence showed 41 amino
      acid residues, which account for an estimated molecular weight of 4520, and eight
      half-cystine residues which cross-link the toxin molecule with four disulfide
      bonds. The molecular weight determined by mass spectrometry was 4518. Comparison
      of this sequence with those from other scorpion toxins showed a resemblance with
      toxins which act on different types of K+ channels. TsTx-IV was able to block
      Ca2+-activated K+ channels of high conductance. TsTX-IV is the first four
      disulfide-bridged short toxin from T. serrulatus so far completely sequenced.

PMID- 10082165
TI  - Spatial structures of the bradykinin potentiating peptide F from Agkistrodon
      piscivorus piscivoris venom.
AB  - Bradykinin potentiating peptides usually show two different activities,
      potentiation of bradykinin and inhibition of angiotensin converting enzyme (ACE).
      Exceptions of this rule have been found suggesting that both effects occur
      independently. This study of peptide F by means of NMR spectroscopy shows clearly
      two different main conformations of the molecule. These different conformations
      may be the reason for the different activities.

PMID- 10082166
TI  - Confirmation of domoic acid production of Pseudo-nitzschia multiseries isolated
      from Ofunato Bay, Japan.
AB  - Production of domoic acid (DA), the responsible toxin for amnesic shellfish
      poisoning, was examined for 44 strains of Pseudo-nitzschia spp. isolated from
      Ofunato Bay, Japan. Only one strain which was identified as Pseudo-nitzschia
      multiseries produced DA in a level comparable to Canadian strains. No significant
      DA was detected in the rest of the strains, indicating that toxic P. multiseries
      does not bloom in a high density in the bay.

PMID- 10082167
TI  - Inhibition of the myotoxic activity of Bothrops asper myotoxin II in mice by
      immunization with its synthetic 13-mer peptide 115-129.
AB  - The region comprising amino acid residues 115-129 of myotoxin II, a Lys49
      phospholipase A2 from the venom of Bothrops asper, was previously shown to
      constitute a heparin binding site, and to be associated with its toxic
      activities. The corresponding synthetic peptide, KKYRYYLKPLCKK, was coupled to
      diphtheria toxoid as a carrier, and utilized as an immunogen in mice, to explore
      the possible protection from the myotoxic activity induced by myotoxin II in
      vivo. Mice receiving peptide-carrier injections produced antibodies to peptide
      115-129, which cross-reacted to myotoxin II, as determined by enzyme-immunoassay.
      In contrast, no antibodies against peptide 115-129 were detected in mice
      immunized with myotoxin II, despite the strong antibody response to the whole
      antigen. Thus, region 115-129 of myotoxin II is not an immunodominant B-cell
      epitope in the mouse. After immunization with conjugated peptide or myotoxin II,
      mice were challenged with myotoxin II, and the extent of myonecrosis was
      estimated by determining their plasma creatine kinase activity, in comparison to
      non-immunized mice. After the challenge, both the group immunized with myotoxin
      II, and the group immunized with peptide 115-129, had a significant reduction of
      myonecrosis. These results demonstrate that region 115-129 of myotoxin II
      constitutes a neutralizing epitope, and provide further evidence for the
      relevance of this region in its myotoxic effect in vivo.

PMID- 10082168
TI  - Isolation of 45-hydroxyyessotoxin from mussels of the Adriatic Sea.
AB  - The diarrhetic shellfish toxin composition in the hepatopancreas of mussels from
      the northern Adriatic sea was investigated. The major toxins were shown to be
      yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxyyessotoxin (45-OHYTX),
      identified by comparison of their chromatographic and spectral properties with
      those reported in the literature.

PMID- 10082169
TI  - Bibliography of toxinology.

PMID- 10082170
TI  - Pharmacokinetic properties of beta-lactamase inhibitors.
AB  - OBJECTIVES: In recent years, the use of combinations of beta-lactam-antibiotics
      with beta-lactamase inhibitors has been proven to be a useful and effective
      strategy to improve upon the therapeutic value of beta-lactam antibiotics. The
      objective of this article is to evaluate the pharmacokinetic properties of three
      commercially available beta-lactamase inhibitors. MATERIALS AND METHODS: Based on
      published articles in the literature, the pharmacokinetic properties of the beta
      lactamase inhibitors clavulanic acid, sulbactam and tazobactam are reviewed and
      compared. RESULTS: There are some considerable differences between these three
      compounds: Only clavulanic acid is orally bioavailable. Tazobactam and sulbactam
      are eliminated renally to a larger extent than clavulanic acid. Tazobactam's
      total body clearance is almost twice that of sulbactam, and the two drugs differ
      significantly in their degree of protein-binding. Furthermore, sulbactam has a
      larger volume of distribution than tazobactam. CONCLUSIONS: When choosing
      combinations of a beta-lactam antibiotic with a beta-lactamase inhibitor, it is
      important to make sure that the pharmacokinetic properties of drug and inhibitor
      are similar and remain similar under changing pathophysiological conditions.
      Hence, beta-lactam inhibitors should not be freely interchanged, but for each
      beta-lactam antibiotic the best partner needs to be identified. If this is done
      properly, fixed combinations of beta-lactam-antibiotic and beta-lactamase
      inhibitor are appropriate and convenient. This situation may represent one of the
      few cases in pharmacotherapy, where fixed combinations of two drugs are
      beneficial.

PMID- 10082171
TI  - Smoking tobacco, microcirculatory changes and the role of nicotine.

PMID- 10082172
TI  - Effects of imipenem and meropenem on purine content of endothelial cells.
AB  - Intravenous compatibility of antibacterial agents has been tested in animal
      models. Use of human umbilical venous endothelial cells (HUVEC) to test
      antibiotic solutions for intravenous tolerance provides a valuable alternate
      model. OBJECTIVE: Evaluation of the effect of imipenem and meropenem on
      intracellular purines reflecting viability, energy production, signal
      transduction, and DNA/RNA synthesis of these cells. MATERIALS AND METHODS: Levels
      of intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP),
      guanosine 5' triphosphate (GTP) and guanosine 5' diphosphate (GDP) were measured
      by means of high performance liquid chromatography (HPLC). RESULTS: The total
      amount of ATP after incubation of cells with 10.0 mg/ml imipenem and meropenem
      for 20 minutes (12.93 +/- 0.93 nmol/million cells and 13.27 +/- 0.89 nmol/million
      cells, respectively) did not result in a decrease compared to controls (12.34 +/-
      0.87 nmol/million cells). In addition, ATP levels were maintained or actually
      increased after 60 minutes. Incubation of cells with 5.0 mg/ml and 2.5 mg/ml of
      imipenem or meropenem for 20 and 60 minutes showed similar results. Purine
      nucleotide profiles of ADP, GTP, GDP following exposure of 10.0 mg/ml, 5.0 mg/ml
      and 2.5 mg/ml of imipenem and meropenem did not differ markedly. CONCLUSIONS:
      These in vitro data show an excellent endothelial compatibility of imipenem and
      meropenem even in high concentrations.

PMID- 10082173
TI  - V. A new route, jet injection of lidocaine for skin wheal for painless
      intravenous catheterization.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of intradermal
      lidocaine anesthesia by two jet injectors to the routine needle infiltration and
      to the topical EMLA cream. SUBJECTS AND METHODS: In a randomized, prospective,
      controlled trial, 100 consenting surgicenter patients in a university hospital
      setting were divided into four groups (n = 25, each); intradermal lidocaine
      anesthesia was given either by the conventional 25 g needle/syringe or the Med-E
      Jet or Biojector injector or EMLA cream was applied on the skin. Visual analogue
      pain scores (VAS) or verbal pain intensity scores (PIS) were reported by the
      patients at lidocaine application and i.v. catheterization. Cost was also
      assessed. RESULTS: At lidocaine application, no pain was reported, since
      proportions of VAS = 0 were 25/25 (CI: 0.868, 0.999) with Med-E-Jet; 24/25
      (0.804, 0.991) with Biojector; 25/25 (0.868, 0.999) with EMLA; in contrast to
      pain, 3/25 (0.044, 0.302) with the needle (PP > 0.999). The VAS scores (mean +/-
      SD) were 0.00 +/- 0.00, 0.04 +/- 0.20, 0.00 +/- 0.00, and 2.4 +/- 2.2
      respectively (p < 0.00 1). No pain was reported by proportions of PIS = 0 with
      Med-E-Jet: 25/25 (CI: 0.868, 0.999); with Biojector: 23/25 (0.749, 0.976); EMLA
      25/25 (0,868, 0.999); but pain with the needle: 5/25 (0.090, 0.394) (PP > 0.999).
      The mean +/- SD PIS scores were 0.00 +/- 0.00, 0.16 +/- 0.55, 0.00 +/- 0.00, and
      1.24 +/- 1.00, respectively (p < 0.001). At i.v. catheterization, the proportions
      of VAS = 0 scores were 22/25 with Med-E-Jet (0.698, 0.956); 21/25 (0.651, 0.934)
      with Biojector; but some pain with needle: 6/25 (0.116, 0.436) (PP > 0.999). The
      mean +/- SD VAS scores were: 0.12 +/- 0.33, 0.44 +/- 0.20, and 1.64 +/- 1.50,
      respectively (p < 0.001). No pain was reported by PIS = 0 scores in 24/25 (0.804,
      0.991) with Med-E-Jet; 24/25 (0.804, 0.991) with the Biojector; but pain by zero
      PIS scores 13/25 (0.334, 0.703) in half of the patients in the needle group (PP >
      0.999). The mean +/- SD scores were 0.00 +/- 0.00, 0.00 +/- 0.00, and 0.76 +/-
      0.88, respectively (p < 0.001). The EMLA cream was not evaluated because of
      inadequate duration of application prior to anesthetic induction.
      Cost/application were: Med-E-Jet = $ 0.13; needle = $ 0.50; Biojector = $ 0.94
      and EMLA = $ 3.76. CONCLUSION: Almost completely painless i.v. catheterization by
      jet injection of lidocaine was accomplished, while needle infiltration produced
      pain/discomfort and did not significantly reduce it at the i.v. needle insertion.

PMID- 10082174
TI  - Pharmacokinetic characteristics of a new multiple unit sustained release
      formulation of sodium valproate.
AB  - AIM: Two bioavailability studies were conducted in healthy male volunteers to
      determine the absorption characteristics of a new dosage form of sodium valproate
      consisting of sustained release pellets in a hard gelatine capsule. SUBJECTS,
      MATERIAL AND METHODS: To obtain first data on the in vivo behavior of the new
      multiple unit formulation a single dose pilot study in comparison with an oral
      solution was performed in 6 volunteers. Following the pilot study the
      pharmacokinetics were investigated versus a conventional enteric-coated tablet
      after multiple dosing in 18 volunteers. The volunteers were administered either a
      single or multiple dose of 300 mg sodium valproate. In both studies a wash-out
      period of at least 1 week elapsed between the periods. Valproic acid was
      determined from serum by gas chromatography at intervals suitable for obtaining
      concentration time curves for both regimens. RESULTS: The results of the pilot
      study showed that the valproate concentration in serum following administration
      of the new sustained release capsule increased smoothly and a longer lasting
      plateau was observed as compared with the solution. The average maximum serum
      valproate concentration of 12.5 microg/ml (sustained release capsule) and 24.3
      microg/ml (solution) appeared at 9.3 h and 0.58 h after dosing. The extent of
      valproate absorption as reflected in the AUC data for each formulation was
      equivalent for the new sustained release capsule and reference formulation (AUC0
      infinity: 369 +/- 88.9 and 339 +/- 76.2 microg/ml x h). Data obtained after
      multiple dose administration provided an indication of the consistency of
      valproate absorption from each dosage form. The time concentration profiles
      following twice daily administration of 300 mg sodium valproate in the multiple
      dose study showed that the extent parameters for absorption of valproate
      (AUC(8tau9tau) = 842 +/- 166 microg/ml x h) are equivalent with the enteric
      coated preparation (AUC(8tau9tau) = 823 +/- 139 microg/ml x h). However, the
      fluctuation of the new sustained release formulation (PTF(8tau9tau) = 0.33 +/-
      0.09) is about only one third of the fluctuation observed with the enteric-coated
      formulation (PTF(8tau9tau) = 0.88 +/- 0.22) when administered twice daily.
      CONCLUSION: These data indicate that the new sustained release capsule possesses
      desirable absorption characteristics in a form that allows twice daily or even
      once daily dosing and therefore improves patient compliance.

PMID- 10082175
TI  - Isoniazid and rifampicin rarely cause acute pancreatitis in patients with
      tuberculosis.

PMID- 10082176
TI  - Prognostic methods in medicine.
AB  - Prognosis--the prediction of the course and outcome of disease processes--plays
      an important role in patient management tasks like diagnosis and treatment
      planning. As a result, prognostic models form an integral part of a number of
      systems supporting these tasks. Furthermore, prognostic models constitute
      instruments to evaluate the quality of health care and the consequences of health
      care policies by comparing predictions according to care norms with actual
      results. Approaches to developing prognostic models vary from using traditional
      probabilistic techniques, originating from the field of statistics, to more
      qualitative and model-based techniques, originating from the field of artificial
      intelligence (AI). In this paper, various approaches to constructing prognostic
      models, with emphasis on methods from the field of AI, are described and
      compared.

PMID- 10082177
TI  - Using probabilistic and decision-theoretic methods in treatment and prognosis
      modeling.
AB  - Causal probabilistic networks, also called Bayesian networks, allow both
      qualitative knowledge about the structure of a problem and quantitative
      knowledge, derived from case databases, expert opinion and literature to be
      exploited in the construction of decision support systems for diagnosis,
      treatment and prognosis. This mixing of qualitative and quantitative knowledge
      will be illustrated, using the selection of antibiotics for a subset of patients
      with severe infections. The subset consists of patients where bacteria or fungi
      have been found in the blood. A simple pathophysiological model of infection is
      used to calculate a prognosis, dependent on the choice of antibiotics. A decision
      theoretic approach is used to balance the therapeutic benefit of antibiotic
      treatment against the cost of antibiotics in the form of direct monetary cost,
      side effects and ecological cost. A retrospective trial on patients with bacteria
      or fungi in the blood stemming from the urinary tract indicates that with this
      approach, it may be possible to suggest balanced choices of antibiotics that not
      only achieve greater therapeutic benefit, but also reduce the cost of therapy.

PMID- 10082178
TI  - Explicit temporal models for decision-theoretic planning of clinical management.
AB  - The management of patients over a prolonged period of time is a complicated task
      involving both diagnostic and prognostic reasoning with incomplete and often
      uncertain knowledge. Various formalisations of this type of task exist, but these
      often conceal one or more essential ingredients of the problem. This article
      explores the suitability of partially observable Markov decision processes to
      formalising the planning of clinical management. These processes allow for
      explicit representation of clinical states of the patient, the management
      strategy employed, the objectives of treatment, and the role of time and change
      in reasoning. However, practical application is hampered by their coarse
      representational granularity and complex formulation. It is discussed how
      probabilistic network representations can be used to alleviate these obstacles.
      The resulting method is illustrated with a real-world example from the domain of
      paediatric cardiology.

PMID- 10082179
TI  - An evolutionary approach to constructing prognostic models.
AB  - A prognostic model is sought to determine whether or not patients suffering from
      an uncommon form of cancer will survive. Given a set of case histories, we
      attempt to find the relative weightings of the different variables that are used
      to describe the cases. Our first innovation is to use a diffusion genetic
      algorithm (DGA) to find weightings which will give optimal survival predictions.
      The DGA enables a number of criteria to be satisfied simultaneously, making it
      particularly suitable for model building. A further innovation is a method of
      representing synergies between interacting factors. The evolved model correctly
      predicts 90% of the survivors and 87% of deaths, an improvement over the current
      model. More significantly, the method enables a simple model to be evolved, one
      that produces well-balanced predictions, and one that is relatively easy for
      clinicians to use. The method was validated by running it on a training set made
      up of 90% of the original database and then studying the performance of the
      generated models on a test set consisting of the remaining 10% of the cases.

PMID- 10082180
TI  - Modelling prognostic power of cardiac tests using rough sets.
AB  - Rough sets (Pawlak Z. Rough Sets: Theoretical Aspects of Reasoning about Data,
      Dordrecht: Kluwer Academic Publishers, 1991) is a relatively new approach to
      representing and reasoning with incomplete and uncertain knowledge. This article
      introduces the basic concepts of rough sets and Boolean reasoning (Brown FM.
      Boolean Reasoning: The Logic of Boolean Equations, Dordrecht: Kluwer Academic
      Publishers, 1990). A rough set framework is then set up to investigate the
      prognosis of cardiac events in a set of patients with chest pain that was earlier
      studied by Geleijnse et al. (J Am Coll Cardiol 1996;28(2):447-454). That study
      used logistic regression to find that the single most important independent
      predictor for future hard cardiac events (cardiac death or non-fatal myocardial
      infarction) was an abnormal scintigraphic scan pattern. However, performing a
      scintigraphic scan is a relatively expensive procedure, and may for some patients
      not really be fully necessary as knowledge of the outcome of the scan may be
      redundant with respect to making a prognosis. Using an approach based on rough
      sets, this paper explores how a patient group in need of a scintigraphic scan can
      be identified for subsequent modelling. Identification of such patients may
      potentially contribute to lowering the cost of medical care and to improving its
      quality since, virtually without loss of information, fewer patients may be
      referred for this procedure.

PMID- 10082181
TI  - An evaluation of intelligent prognostic systems for colorectal cancer.
AB  - In this paper we describe attempts at building a robust model for predicting the
      length of survival of patients with colorectal cancer. The aim of the research,
      reported in this paper, is to study the effective utilisation of artificial
      intelligence techniques in the medical domain. We suggest that an important
      research objective of proponents of intelligent prognostic systems must be to
      evaluate the additionality that AI techniques can bring to an already well
      established field of medical prognosis. Towards this end, we compare a number of
      different AI techniques that lend themselves to the task of predicting survival
      in colorectal cancer patients. We describe the pros and cons of each of these
      methods using the usual metrics of accuracy and perspicuity. We then present the
      notion of intelligent hybrid systems and evaluate the role that they may
      potentially play in developing robust prognostic models. In particular we
      evaluate a hybrid system that utilises the k Nearest Neighbour technique in
      conjunction with Genetic Algorithms. We describe a number of innovations used
      within this hybrid paradigm used to build the prognostic model. We discuss the
      issue of censored patients and how this issue can be tackled within the various
      models used. In keeping with our objective of studying the additionality that AI
      techniques bring to building prognostic models, we use Cox's regression as a
      standard and compare each AI technique with it, attempting to discover their
      capabilities in enhancing prognostic methods in medicine. In doing so we address
      two main questions--which model fits the data best?, and are the results obtained
      by the various AI techniques significantly different from those of Cox's
      regression? We conclude this paper by discussing future enhancements to the work
      presented and lessons learned from the study to date.

PMID- 10082182
TI  - The role of psychodynamic psychotherapy in psychiatry.

PMID- 10082183
TI  - What patient characteristics make therapists recommend psychodynamic
      psychotherapy or other treatment forms?
AB  - In order to study factors that psychodynamic therapists considered to be
      important for recommendation of treatment, psychiatric diagnoses (DSM-III-R Axes
      I and II and the GAF) as well as character traits assessed by the Karolinska
      Psychodynamic Profile (KAPP) were retrospectively assessed in interview case
      notes of patients applying for psychodynamic psychotherapy. Recommendation of
      psychotherapy was predicted by the absence of a personality disorder and high GAF
      scores, but not by the presence of a psychiatric syndrome. The KAPP
      differentiated between patients with and without disorders on Axis II, but not on
      Axis I. Patients who were recommended psychodynamic psychotherapy were healthier
      on all central KAPP variables compared to those who were recommended other
      treatments, and they were also characterized by predominantly neurotic
      personality organization, with inhibition as the most prominent defence.

PMID- 10082184
TI  - Seasonal affective disorders among rural Finns and Lapps.
AB  - We investigated the prevalence of seasonal affective disorder (SAD) and
      subsyndromal SAD (S-SAD) in rural populations in south-western and northern
      Finland by using the Seasonal Pattern Assessment Questionnaire (SPAQ). A total of
      1710 SPAQs were analysed. The prevalences of overall SAD and S-SAD were 12.0% and
      27.1%, respectively. Winter SAD (W-SAD) was the most common type, with
      prevalences of 9.5% for W-SAD and 18.4% for W-S-SAD. The prevalences of overall
      and winter SAD did not differ between Finns living in northern and south-western
      Finland. Among the Lapps, W-SAD cases were less frequent than among the Finns in
      Lapland. Overall seasonality correlated significantly with female gender, high
      body mass index, high level of education and young age.

PMID- 10082185
TI  - Mortality among discharged psychiatric patients in Finland.
AB  - No comprehensive study has yet been made of mortality among psychiatric patients
      in Finland. According to studies conducted in other parts of the world, the
      mortality rates of psychiatric patients are higher than those of the general
      population. The study population here consisted of all patients discharged from
      psychiatric hospitals during the year 1988 (n = 22940). The register follow-up of
      these patients extended up to the year 1992. In the course of the follow-up a
      total of 3936 discharged psychiatric patients died (17.2%). The standardized
      mortality ratio (SMR) of the patients discharged from psychiatric hospitals was
      almost four times higher than that of the general population. The proportion of
      unnatural causes of death, including accidents in the young age groups and
      especially the much higher suicide SMR among young women, is a particularly
      striking finding. Natural causes of death were also more prevalent among the
      study population than in the general population, the major causes being acute
      myocardial infarction and unspecified pneumonia. The results of this study
      confirm previous findings of increased mortality among psychiatric patients
      compared to the general population. On the basis of this study one cannot,
      however, conclude that the reason for the high mortality rate would be premature
      discharge. More attention needs to be paid to the care of young patients and to
      supporting the patient during the transition from the hospital to community care.

PMID- 10082186
TI  - Long-term prognosis of bipolar I disorder.
AB  - This study examined the contribution of demographic, syndromal and longitudinal
      course variables to the long-term prognosis of 165 bipolar patients prospectively
      observed over 10 years as part of the National Institute of Mental Health
      Collaborative Study of Depression. Although most baseline clinical and
      demographic variables were not strong prognostic indicators, switching polarity
      within episodes was. Most episodes among the poor-prognosis patients were
      polyphasic, while most episodes among the comparison group with a better
      prognosis were monophasic. There was no evidence of shortening of cycle lengths
      over follow-up for either the poor-prognosis group or the entire sample. The
      relevance of these findings to the 'kindling' model is discussed.

PMID- 10082187
TI  - Costs of services for schizophrenic patients in Norway.
AB  - Estimates of the direct costs of mental health services for patients with
      schizophrenia are made from a registration of all patients seen during a period
      of 4 weeks in all treatment units serving 6 catchment areas. The estimates were
      based on unit costs. The total direct costs of mental health services for
      schizophrenic patients in Norway were estimated to be NOK 1158 million (US$ 164
      million). In total, 74.3% of the costs are for long-term in-patient care, 19.7%
      are for acute and intermediate length in-patient care, and 6.0% are for out
      patient and day care. The average costs of schizophrenic patients with a GAF
      score of 1-20 are almost twice those of patients with a GAF score of 21-40, and
      more than three times those of patients with a GAF score of 41-60.

PMID- 10082188
TI  - Consultation of mental health professionals by French adolescents with probable
      psychiatric problems.
AB  - A national sample of school-attending adolescents aged 12-20 years (n = 8435)
      filled out an anonymous self-administered questionnaire. We considered a group of
      868 adolescents with probable psychiatric problems (PPP) in order to identify
      personal, psychological and environmental factors as well as help-seeking
      behaviour associated with consultation of mental health professionals (MHP).
      Among the adolescents with PPP, 13.7% consulted MHP at least once during the
      year. Logistic regression analysis showed that consultation with MHP was more
      frequent for adolescents with multiple problems (OR = 2.3), functional physical
      disorders (OR = 1.9), family problems (OR = 2), separated parents (OR = 4.4) or
      multiple contacts with other doctors (GP, school doctor and other specialists, OR
      = 2.2, 3.6 and 2.6, respectively), and among those who confided in teachers or
      youth group advisors (OR = 2.2). Those who confided in peers consulted MHP less
      often (OR = 0.5). However, consultation with MHP was not associated with other
      sociodemographic or educational characteristics, with type of problem
      (internalized or externalized), or with confiding in one's parents.

PMID- 10082189
TI  - Patterns of comorbidity in relation to functioning (GAF) among general hospital
      psychiatric referrals. European Consultation-Liaison Workgroup.
AB  - Improvement of services for physically ill patients with concurrent psychiatric
      problems is a noteworthy issue in general hospitals. Among 1249 general hospital
      in-patients referred for psychiatric consultation, concurrent mental and
      behavioural disorders (ICD-10) were diagnosed in 84% of cases. Any concurrent
      mental and behavioural disorder was associated with dramatically low functioning
      (GAF = 46), indicating serious psychosocial impairment. This is a striking new
      finding of clinical importance. The effect on functioning was similar for
      substance use disorders, other mental disorders, and combined mental and
      substance use disorders (dual diagnoses), with no gender differences. This
      finding highlights the need for specialized interventions among general hospital
      in-patients referred for psychiatric consultation.

PMID- 10082190
TI  - Criteria defining refractory schizophrenia.
AB  - To date there has been no agreement with regard to the criteria that define
      refractory schizophrenia. In this study, we intended to clarify the criteria
      which psychiatrists use to judge schizophrenic patients as being refractory in
      Japan. Based on 258 schizophrenic in-patients (ICD-10) and their likelihood of
      discharge, level of psychosocial functioning, mental state and use of medication,
      the common features of patients who are viewed as non-dischargeable because of
      their severe mental state, compared to those of dischargeable patients, were
      extracted and used as the criteria. The criteria proposed necessitate (i)
      diagnosis of schizophrenia by standard operational criteria, (ii) continuous
      hospitalization for at least the past 2 years, (iii) a level of psychosocial
      functioning of < or = 40 as measured by the Global Assessment Scale, and (iv) an
      intensity score of 'marked' or 'severe' on at least three of the six Manchester
      Scale items (flattened affect, psychomotor retardation, delusions,
      hallucinations, incoherence of speech and poverty of speech).

PMID- 10082191
TI  - Social deficits associated with schizophrenia defined in terms of interpersonal
      Machiavellianism.
AB  - The social deficits of schizophrenia have been interpreted in an evolutionary
      context of Machiavellian social dexterity, stressing deficits in evolved
      psychological mechanisms that mediate the interpretation of affect and deceptive
      intention in others. A complementary hypothesis was tested, that patients with
      schizophrenia will be relatively non-Machiavellian compared to controls, and that
      social problems associated with the condition may reflect this relative social
      credulity. This hypothesis was addressed by assessing Mach IV psychometric scale
      performance in a group of 51 patients with schizophrenia and in 93 controls.
      Males, but not females, with schizophrenia scored significantly lower on the Mach
      IV scale than control groups. This result is interpreted in conjunction with the
      existing literature on social competence and sex differences in the
      symptomatology of patients with schizophrenia.

PMID- 10082192
TI  - Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor,
      against closed head injury in the mouse.
AB  - The potential neuroprotective effects of rasagiline, N-propargyl-1R-aminoindan, a
      selective monoamine oxidase-B inhibitor and its inactive enantiomer TVP 1022, N
      propargyl-1S-aminoindan were assessed against the sequelae of closed head injury
      in the mouse. Injury was induced in the left hemisphere under ether anaesthesia.
      Rasagiline (0.2 and 1 mg/kg) or TVP1022 (1 and 2 mg/kg) injected 5 min after
      injury accelerated the recovery of motor function and spatial memory and reduced
      the cerebral oedema by about 40-50%, (P < 0.01). The neuroprotective effects on
      motor function and spatial memory, but not on cerebral oedema, were prevented by
      scopolamine (0.2 mg/kg). Daily injection of rasagiline (1 mg/kg) from day 3 after
      injury accelerated the recovery of spatial memory but not motor function.
      CONCLUSIONS: Early administration of rasagiline or TVP1022 can reduce the
      immediate sequelae of brain injury. The mechanism of action does not appear to
      involve monoamine oxidase-B inhibition but could be mediated by the maintenance
      of cholinergic transmission in brain neurons.

PMID- 10082193
TI  - N(G)-nitro-L-arginine impairs the anticonvulsive action of ethosuximide against
      pentylenetetrazol.
AB  - N(G)-nitro-L-arginine (NNA; an inhibitor of nitric oxide synthase) in a dose of
      40 mg/kg impaired the protective activity of ethosuximide against the clonic
      phase of pentylenetetrazol-induced seizures in mice. The ED50 value of
      ethosuximide was significantly increased from 108 to 158 mg/kg. NNA (40 mg/kg)
      was ineffective against the protective effects of diazepam, phenobarbital and
      valproate against pentylenetetrazol-induced seizures. NNA (40 mg/kg) did not
      influence the plasma levels of the antiepileptic drugs studied, so a
      pharmacokinetic interaction is not probable. L-Arginine (500 mg/kg) prevented the
      NNA-induced reduction of the anticonvulsive activity of ethosuximide. It can be
      concluded that nitric oxide participates in the expression of the anticonvulsive
      action of ethosuximide, but not that of diazepam, phenobarbital and valproate,
      against pentylenetetrazol-induced seizures.

PMID- 10082194
TI  - Excessive release of [3H]noradrenaline and glutamate in response to simulation of
      ischemic conditions in rat spinal cord slice preparation: effect of NMDA and AMPA
      receptor antagonists.
AB  - In the present study we investigated the effects of NMDA and non-NMDA glutamate
      receptor antagonists on the ischemia-evoked release of [3H]noradrenaline from rat
      spinal cord slices. An in vitro ischemia model (oxygen and glucose deprivation)
      was used to simulate the ischemic conditions known to cause neuronal injury.
      Spinal cord slices were loaded with [3H]noradrenaline and superfused with Krebs
      solution in a micro-organ bath. Both axonal stimulation and ischemia increased
      the release of [3H]noradrenaline, but the release in response to glucose and
      oxygen deprivation was [Ca2+]o independent. Dizocilpine (MK-801), an NMDA
      receptor antagonist, suppressed the release of [3H]noradrenaline produced by
      ischemia, while it enhanced the release of [3H]noradrenaline evoked by electrical
      field stimulation. In contrast, LY300168 (GYKI-53655) [(+/-)-3-N-methylcarbamyde
      1-(4-aminophenyl)-4-methyl-1.8-methylen e-dioxy-5H-2.3-benzodiazepine] and its (
      )isomer LY303070 (GYKI-53784) [(-)-3-N-methylcarbamyde-1-(4-aminophenyl)-4-methyl
      1.8-methylene- dioxy-5H-2.3-benzodiazepine] AMPA receptor antagonists, had no
      effect on the release of [3H]noradrenaline evoked by either electrical
      stimulation or ischemia. Desipramine, a noradrenaline uptake inhibitor,
      potentiated the release of [3H]noradrenaline evoked by ischemia, while in the
      absence of [Ca2+]o but under conditions when [3H]noradrenaline release was
      further increased, it reduced the release. Dizocilpine also decreased glutamate
      and aspartate release, measured by high performance liquid chromatography, during
      ischemia. It is concluded that glutamate release and NMDA receptors, but not AMPA
      receptors, are involved in the acute effect of oxygen and glucose deprivation on
      the excessive release of noradrenaline and that this release is not related to
      physiological axonal conduction.

PMID- 10082195
TI  - Induction of long-lasting depression by (+)-alpha-methyl-4-carboxyphenylglycine
      and other group II mGlu receptor ligands in the dentate gyrus of the hippocampus
      in vitro.
AB  - Application of several well characterized group II mGlu receptor ligands was
      found to induce a long-lasting depression of synaptic transmission in the medial
      perforant path of the dentate gyrus. These ligands were N-acetylaspartylglutamate
      (NAAG), which is a dipeptide located in the brain and possibly functioning as a
      neurotransmitter, two agents widely used previously as mGluR antagonists, (+)
      alpha-methyl-4-carboxyphenylglycine (MCPG), and (S)-alpha-ethylglutamate (EGLU),
      and the well characterized group II mGluR agonist (2S,1R,2R,3R)-2
      (2S,1'R,2'R,3'R)-2(2'3'-dicarboxycyclopropyl)glyci ne (DCG-IV). It is postulated
      that all these ligands induced the long-lasting depression by an agonist/partial
      agonist action at group II mGlu receptor. The long-lasting depression induced by
      the ligands showed mutual occlusion with low frequency stimulation-induced long
      term depression, demonstrating common induction or maintenance mechanisms. The
      induction of the long-lasting depression by the mGlu receptor ligands are
      suggested to occur postsynaptically as the induction was not associated with a
      change in paired pulse depression of excitatory postsynaptic potentials (EPSPs).

PMID- 10082196
TI  - Presence of dinucleotide and ATP receptors in human cerebrocortical synaptic
      terminals.
AB  - Human cerebrocortical synaptic terminals elicited concentration-dependent Ca2+
      transients after Ap5A (diadenosine pentaphosphate) and ATP stimulation, with EC50
      values of 23.44 +/- 3.70 microM and 11.48 +/- 2.12 microM, respectively. The lack
      of cross-desensitisation and the selective antagonism by Ip5I (diinosine
      pentaphosphate), suggests the activation of a dinucleotide receptor by Ap5A, and
      a P2X receptor by ATP. Ap5A Ca2+ transients were partially abolished by omega
      conotoxin GVI-A (53%), suggesting the participation of a N-type Ca2+ channel in
      the dinucleotide response. ATP effect on Ca2+ entry was abolished by nicardipine
      (44%) and by omega-conotoxin GVI-A (52%), suggesting the participation of L- and
      N-type Ca2+ channels. These data suggest that Ap5A and ATP activate dinucleotide
      and P2X receptors, respectively, in human brain synaptic terminals.

PMID- 10082197
TI  - Arrhythmias induced by myocardial ischaemia-reperfusion are sensitive to
      ionotropic excitatory amino acid receptor antagonists.
AB  - We have investigated the effects of (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), a non-competitive N
      methyl-D-aspartate (NMDA) ionotropic excitatory amino acid receptor antagonist,
      and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA ionotropic excitatory
      amino acid receptor antagonist, ketamine and memantine, NMDA receptor channel
      blockers, on ventricular arrhythmias induced by myocardial ischaemia and
      myocardial ischaemia-reperfusion. Coronary artery occlusion caused 100 +/- 2%
      ventricular tachycardia, in saline treated group, and 60 +/- 3% ventricular
      fibrillation. 66 +/- 6% of the animals recovered from ventricular fibrillation,
      while in 34 +/- 4% of animals the ventricular fibrillation caused mortality. The
      incidence of ventricular tachycardia, ventricular fibrillation and mortality was
      not modified by treatment of rats with MK801 (0.3 mg/kg i.v.), CNQX (1 mg/kg
      i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg), injected 5 min prior to
      occlusion. Reperfusion caused severe arrhythmias which started within 5 +/- 2 s.
      For instance, in the saline treated group, the incidence of ventricular
      tachycardia was 100 +/- 5%, while ventricular fibrillation occurred in 87 +/- 3%
      of the animals and lasted 90 +/- 12 s. The mortality was 62 +/- 6%. The incidence
      of ventricular tachycardia, ventricular fibrillation and mortality induced by
      reperfusion was greatly (P < 0.01) reduced in animals treated with MK801 (0.3
      mg/kg i.v.), CNQX (1 mg/kg i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg),
      injected 5 min prior to occlusion. Therefore, reperfusion-induced arrhythmias,
      but not ischaemia-induced arrhythmias, are sensitive to NMDA/non-NMDA ionotropic
      excitatory amino acid receptor antagonists.

PMID- 10082198
TI  - Bilateral kidney ligation abolishes pressor response to N(G)-nitro-D-arginine.
AB  - We have shown that N(G)-nitro-D-arginine (D-NNA) is 50% as potent as N(G)-nitro-L
      arginine (L-NNA) in causing pressor response and 2-3% as potent as L-NNA in
      inhibiting endothelium-dependent relaxation in vitro. These results suggest in
      vivo activation of D-NNA. Furthermore, the potency of D-NNA was markedly
      increased after it had been incubated with homogenate of the kidney, but not
      plasma or homogenate of the aorta, lungs or liver. This study examined if
      bilateral ligation of the kidneys attenuated the biological action of D-NNA. I.v.
      bolus of D-NNA (16 mg/kg), L-NNA (3 mg/kg) and norepinephrine (0.25-16 microg/kg)
      increased arterial pressure in sham-operated rats. Bilateral ligation of the
      kidneys abolished pressor response to D-NNA, but not L-NNA and norepinephrine.
      I.v. bolus D-NNA in sham-operated rats, but not kidney-ligated rats, inhibited
      relaxation response to acetylcholine in pre-constricted aortic rings ex vivo.
      These results indicate that the kidney is the primary organ which activates D
      NNA.

PMID- 10082199
TI  - 2,5-Di-t-butyl-1,4-benzohydroquinone induces endothelium-dependent relaxation of
      rat thoracic aorta.
AB  - The aim of this work was to clarify the mechanism by which 2,5-di-t-butyl-1,4
      benzohydroquinone (BHQ) induces relaxation of rat thoracic aorta. In particular,
      the role of endothelium-derived nitric oxide (NO) was investigated. BHQ
      concentration dependently (0.1-10 microM) relaxed rat aorta rings precontracted
      with phenylephrine. This effect was dependent on the intactness of the
      endothelium, suppressed by preincubation with 100 microM N(omega)-nitro-L
      arginine methyl ester and antagonised by 3-30 microM methylene blue. The 10
      microM BHQ-induced relaxation, however, was followed by the gradual and slow
      return to phenylephrine-induced tone. Superoxide dismutase (250 U/ml) increased
      the BHQ-induced relaxation, while preincubation with 3 mM diethyldithiocarbamate
      inhibited it in a time-dependent fashion. BHQ gave rise to superoxide anion
      formation which was markedly inhibited by the addition of superoxide dismutase
      (250 U/ml), either in the presence or in the absence of aorta rings. The non
      specific blocker of Ca2+ channels, Ni2+, concentration dependently attenuated the
      BHQ relaxing effect. BHQ did not modify the relaxation induced by the NO donor 3
      morpholino-sydnonimine in endothelium-deprived rings. In conclusion, BHQ induces
      endothelium-dependent relaxation and gives rise, by auto-oxidation, to the
      formation of superoxide anion. The former effect results from the enhanced
      synthesis of NO rather than from its enhanced biological activity; NO synthase is
      presumed to be stimulated by BHQ-induced activation of Ca2+ influx through Ni2+
      sensitive Ca2+ channels.

PMID- 10082200
TI  - Pharmacology of A-216546: a highly selective antagonist for endothelin ET(A)
      receptor.
AB  - Endothelins, 21-amino acid peptides involved in the pathogenesis of various
      diseases, bind to endothelin ET(A) and ET(B) receptors to initiate their effects.
      Here, we characterize the pharmacology of A-216546 ([2S-(2,2-dimethylpentyl)-4S
      (7-methoxy-1,3-benzodioxol-5-yl )-1-(N,N-di(n-butyl) aminocarbonylmethyl)
      pyrrolidine-3R-carboxylic acid), a potent antagonist with > 25,000-fold
      selectivity for the endothelin ET(A) receptor. A-216546 inhibited
      [125I]endothelin-1 binding to cloned human endothelin ET(A) and ET(B) receptors
      competitively with Ki of 0.46 and 13,000 nM, and blocked endothelin-1-induced
      arachidonic acid release and phosphatidylinositol hydrolysis with IC50 of 0.59
      and 3 nM, respectively. In isolated vessels, A-216546 inhibited endothelin ET(A)
      receptor-mediated endothelin-1-induced vasoconstriction, and endothelin ET(B)
      receptor-mediated sarafotoxin 6c-induced vasoconstriction with pA2 of 8.29 and
      4.57, respectively. A-216546 was orally available in rat, dog and monkey. In
      vivo, A-216546 dose-dependently blocked endothelin-1-induced pressor response in
      conscious rats. Maximal inhibition remained constant for at least 8 h after
      dosing. In conclusion, A-216546 is a potent, highly endothelin ET(A) receptor
      selective and orally available antagonist, and will be useful for treating
      endothelin-1-mediated diseases.

PMID- 10082201
TI  - Temporary and partial inhibition of platelets by SM-20302 prevents coronary
      artery thrombosis in a chronic canine model.
AB  - We proposed that temporary and partial platelet inhibition by a GPIIb/IIIa
      receptor antagonist, SM-20302, would provide sustained antithrombotic efficacy in
      a chronic model of coronary artery thrombosis. Instrumented, conscious dogs
      received vehicle (Group I, n = 7), low dose SM-20302 (30 microg/kg bolus + 1
      microg/kg/min infusion for 6 h) (Group II, n = 7), or high dose SM-20302 (100
      microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group III, n = 7).
      Thrombosis was initiated by electrolytic injury to the circumflex coronary
      artery. Coronary blood flow was monitored for 6 h on day 1 and days 2-6. Platelet
      aggregation was performed in platelet-rich plasma prepared from citrated or
      heparinized blood. At 6 h, both doses of SM-20302 inhibited adenosine diphosphate
      induced platelet aggregation completely (> 90%) in citrated platelet-rich plasma,
      but incompletely (57-59%) in heparinized platelet-rich plasma. Platelet
      reactivity returned to baseline values at 24 h. Control animals developed
      thrombotic occlusion on Day 1. Both doses of SM-20302 maintained vessel patency
      during the infusion period (Day 1) and the subsequent 5 days. Myocardial infarct
      size and mortality in the drug treated groups were reduced compared to the
      vehicle group. Thus, temporary inhibition of platelet reactivity by SM-20302 is
      associated with sustained prevention of primary thrombus formation, and reduction
      in infarct size and mortality.

PMID- 10082202
TI  - Agonist-dependent difference in the relationship between cytosolic Ca2+ level and
      release of vascular relaxing factors in the endothelium of rabbit aortic valve.
AB  - The correlation between changes in cytosolic Ca2+ levels ([Ca2+]i) and the
      release of vascular relaxing factor(s) was investigated in the endothelium of
      rabbit aortic valve. ATP, carbachol and thapsigargin increased endothelial
      [Ca2+]i in rabbit aortic valve loaded with a leakage resistant, fluorescent Ca2+
      indicator, fura-PE3. Release of relaxing factors was bioassayed using the
      'sandwich' preparation in which contraction was measured in the endothelium
      denuded rabbit aorta attached to the endothelial surface of the valve. Addition
      of ATP, carbachol and thapsigargin induced sustained relaxation of the
      phenylephrine-induced contraction of the aorta in the 'sandwich' preparation.
      N(G)-monomethyl-L-arginine (L-NMMA) greatly attenuated the relaxation induced by
      carbachol, and combined treatment with tetra-n-butylammonium completely inhibited
      the relaxation. These results suggest that the endothelial relaxing factors
      released from aortic valve are nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF). When the increase in endothelial [Ca2+]i was
      plotted against the relaxation, the carbachol-induced increase in [Ca2+]i
      elicited greater relaxation than did ATP or thapsigargin at a given [Ca2+]i. This
      suggests that various agonists differently modulate the relationship between
      [Ca2+]i and release of NO.

PMID- 10082203
TI  - Transient and sustained impacts of hydroxyl radicals on sarcoplasmic reticulum
      function: protective effects of nebivolol.
AB  - The hydroxyl radical (*OH) is a very reactive oxygen-free radical species that
      has profound effects on myocardial contractility. We investigated the impact of
      *OH on free radical induced injury in right ventricular rabbit cardiac
      trabeculae. Additionally, we investigated the protective properties of the beta
      adrenoceptor antagonist nebivolol. The contractile response to a brief, 2 min
      exposure to *OH consisted of a severe but transient rigor-like contracture,
      followed by a new steady state in which diastolic force (Fdia) remained increased
      and developed force (Fdev) remained decreased. In the new steady state
      sarcoplasmic reticulum function only partly recovered, reflected by a > 50%
      blunted force-frequency relationship. In the presence of nebivolol (10(-6) M),
      during the early phase the increase in Fdia was significantly smaller, and
      recovered better while Fdev was higher during peak. Moreover, nebivolol
      completely abolished blunting of the force-frequency relationship, which was
      observed in the sustained *OH injury phase. The results indicate that hydroxyl
      radical injury induces systolic and diastolic dysfunction, and that nebivolol can
      effectively prevent a large part of this *OH injury.

PMID- 10082204
TI  - Gender difference in levels of alpha2-adrenoceptor mRNA in the rat tail artery.
AB  - To investigate the hypothesis that differing mRNA levels underlie gender
      differences in the contractile response of the rat tail artery, alpha2
      adrenoceptor mRNA was measured using in situ hybridization. Messenger RNA for the
      alpha2A- and alpha2C-adrenoceptor subtypes was found localized to the smooth
      muscle layer. There was no detectable mRNA present for the alpha2B-adrenoceptor
      subtype. Levels of alpha2C-adrenoceptor mRNA were greater in female compared to
      male tail arteries (417 +/- 35 vs. 263 +/- 38 dpm/mg, P = 0.01), while levels of
      alpha2A-adrenoceptor mRNA were the same in both sexes. Levels of alpha2
      adrenoceptor mRNA may parallel levels of functioning protein present in the rat
      tail artery.

PMID- 10082205
TI  - Impairment of endothelium-dependent relaxation in the arteries cultured with
      fetal bovine serum.
AB  - Effects of chronic treatment with fetal bovine serum on the function of vascular
      endothelium were examined using an organ culture system. In the rabbit mesenteric
      arteries cultured with 10% fetal bovine serum for 7 days, the substance P- or
      ionomycin-induced endothelium-dependent relaxation was significantly attenuated
      compared to the arteries cultured in the serum-free condition. The effects of the
      serum were concentration- and time-dependent. By the treatment with the serum,
      the amounts of nitric oxide (NO) production and total mRNA for endothelial NO
      synthase were reduced, whereas the sodium nitroprusside-induced relaxation was
      rather augmented. These results suggest that chronic treatment of rabbit
      mesenteric artery with fetal bovine serum decreases endothelial NO synthase mRNA,
      reduces NO production and impairs endothelium-dependent relaxation.

PMID- 10082206
TI  - Inhibition of emesis by tachykinin NK1 receptor antagonists in Suncus murinus
      (house musk shrew).
AB  - The anti-emetic potential of CP-122,721 ((+)-2S,3S)-3-(2-methoxy-5
      trifluoromethoxybenzyl)amino-2-phenylpi peridine), CP-99,994 ((+)-(2S,3S)-3-(2
      methoxybenzylamino)-2-phenylpiperidine), CP-100,263 ((-)-(2R,3R)-3-(2
      methoxybenzylamino)-2-phenylpiperidine), RP 67580 ((3R, 7aR)-7,7-diphenyl-2-[1
      imino-2-(2-methoxyphenyl)ethyl] po-hydroisoindol-4-one), FK 888 (N2-[(4R)-4
      hydroxy-1-(1-methyl-1H-in-dole-3-yl)carbonyl-L-propyl] -N-methyl-N-phenylmethyl-1
      3-(2-naphthyl)-alaninamide) and GR 82334 ([D-Pro9[spiro-g-lactam]Leu10]
      physalaemin-(1-11)) was investigated to inhibit nicotine (5 mg/kg, s.c.)-, copper
      sulphate pentahydrate (120 mg/kg, intragastric)- and motion (4 cm horizontal
      displacement at 1 Hz for 5 min)-induced emesis in Suncus murinus. A 30 min
      intraperitoneal pre-treatment with CP-122,721, CP-99,994, RP 67580 and FK 888
      significantly (P < 0.05) antagonized nicotine-induced emesis with ID50 values of
      2.1, 2.3, 13.5 and 19.2 mg/kg, respectively CP-100,263, the less active
      enantiomer of CP-99,994, was inactive at doses up to 10 mg/kg. Infusion of GR
      82334, CP-122,721, CP-99,994 and FK 888 into the dorsal vagal complex of the
      hindbrain also antagonized nicotine-induced emesis yielding ID50 values of 1.1,
      3.0, 3.3 and 58.0 microg/dorsal vagal complex, respectively RP 67580 and CP
      100,263 were inactive. RP 67580 and FK 888 failed to antagonize copper sulphate
      induced emesis but CP-122,721 and CP-99,994 were active yielding ID50 values of
      2.2 and 3.0 mg/kg, i.p., respectively. CP-99,994 also completely prevented motion
      induced emesis at 10 mg/kg, i.p. (P < 0.05) and RP 67580 produced a significant
      reduction of motion-induced emesis at 10 mg/kg, i.p. (P < 0.05). These studies
      provide evidence of a central site of action of tachykinin NK1 receptor
      antagonists to inhibit nicotine-induced emesis in S. murinus and confirm the
      broad profile of inhibitory action. The rank order of potency of the antagonists
      following the intra-dorsal vagal complex administration suggests that the S.
      murinus tachykinin NK1 receptor has a unique pharmacological profile.

PMID- 10082207
TI  - Effect of DP-1904, a thromboxane synthetase inhibitor, on antigen- and spasmogen
      induced bronchoconstriction in rodents.
AB  - The effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetra-hydronaphthalene-2
      car boxylic acid hydrochloride], a selective thromboxane synthetase inhibitor,
      was examined on antigen- and spasmogen-induced bronchoconstriction in rodents.
      Oral administration of DP-1904 (1, 3, 10 mg/kg) as well as OKY-046 (sodium (E)
      3[4-(1-imidazolylmethyl)-phenyl]-2-propanoate, 100 mg/kg), significantly
      inhibited immunoglobulin G-mediated bronchoconstriction in actively sensitized
      guinea pigs. Immunoglobulin E-mediated bronchoconstriction in actively sensitized
      rats was also inhibited by both DP-1904 (1, 10 mg/kg) and OKY-046 (100 mg/kg). DP
      1904 (3-30 mg/kg) and OKY-046 (30 mg/kg) suppressed leukotriene D4-induced
      bronchoconstriction in guinea pigs. In these models, the endogenous levels of
      thromboxanes significantly increased following the stimulus (antigen and
      leukotriene D4). DP-1904 (10 mg/kg) inhibited the increase in thromboxane level
      in both plasma and bronchial alveolar lavage fluid. These actions of DP-1904
      persisted for more than 12 h, indicating a long-lasting effect of DP-1904 on
      bronchoconstriction. The results showed that the biological activity of DP-1904
      in our rodents models is more potent than that of OKY-046 (Ozagrel), which is
      available as an anti-asthma agent in Japan.

PMID- 10082208
TI  - Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in
      dihydroetorphine-dependent mice.
AB  - The immunomodulatory effects of dihydroetorphine were systematically investigated
      in subchronically treated mice. In a dose-dependent fashion, dihydroetorphine
      (total doses at 444.5, 889 and 1778 microg/kg) lowered the increase of body
      weight, decreased the weight of the spleen and thymus, weakened the delayed-type
      hypersensitivity, reduced the generation of antibody-forming cells, inhibited
      splenic lymphocyte proliferation induced by concanavalin A and
      lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant
      of splenocytes induced by concanavalin A, and depleted the ratio of CD4+ and CD8+
      subpopulations. Moreover, the physical dependence on dihydroetorphine was also
      evaluated to confirm that the immunosuppression was concomitant with the
      addiction to the drug. These results demonstrate that subchronic treatment with
      dihydroetorphine dose dependently suppresses both humoral and cell-mediated
      immune function, and that the immunosuppressive effects of dihydroetorphine are
      much more potent than those of morphine.

PMID- 10082209
TI  - Inhibition of P-selectin attenuates neutrophil-mediated myocardial dysfunction in
      isolated rat heart.
AB  - The expression of P-selectin on postischemic endothelium after reperfusion has
      been shown to trigger neutrophil attachment and the subsequent inflammatory
      responses. Extensive studies have demonstrated that P-selectin is involved in the
      progression of neutrophil-mediated myocardial infarction and no-reflow
      phenomenon. In the present study, we examined the effects of selectin inhibitors,
      sialyl Lewis X-oligosaccharide and anti-P-selectin monoclonal antibody, PB1.3 on
      neutrophil-dependent left ventricular dysfunction in isolated rat heart. The
      hearts were subjected to global ischemia for 20 min and then reperfused for 45
      min with rat plasma in the presence of human neutrophils during the first 5 min
      of the reperfusion. Left ventricular developed pressure and other parameters of
      the left ventricular function deteriorated throughout the reperfusion period in a
      neutrophil-dependent manner. In contrast, the coronary flow was reduced early on
      (< 15 min) but recovered to the level in the hearts reperfused with no
      neutrophils 45 min after the reperfusion. We examined the effects of selectin
      inhibitors under experimental conditions in which the hearts were perfused with
      30 million neutrophils. The treatment with sialyl Lewis X-oligosaccharide at a
      dose of 0.3 mg/min resulted in amelioration of left ventricular developed
      pressure to 57.2 +/- 14%, compared to 26.1 +/- 4.3% in the saline-treated group
      (P < 0.05). Similarly, the treatment with mouse anti-human P-selectin monoclonal
      antibody (IgG1) PB1.3 at a dose of 0.6 mg/min resulted in the prominent recovery
      of left ventricular developed pressure after 45 min of reperfusion (59.9 +/- 9.3%
      vs. 26.1 +/- 4.3% in the saline-treated group, P < 0.05). PB1.3 also attenuated
      the elevation of left ventricular end-diastolic pressure compared to that of the
      saline-treated group during the reperfusion period. Moreover, the treatment with
      PB1.3 ameliorated the recovery of coronary flow until 10 min after the
      reperfusion and the recovery of coronary flow 10 min after the reperfusion was
      55.2 +/- 9.2%, as compared to 28.2 +/- 7.7% in saline-treated hearts (P < 0.05).
      To our knowledge, this is the first direct demonstration that the specific
      inhibition of P-selectin results in the inhibition of neutrophil-mediated left
      ventricular dysfunction or myocardial stunning.

PMID- 10082210
TI  - Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells:
      differential role of P/Q- and L-type Ca2+ channels.
AB  - Phorbol esters reduce depolarization-evoked Ca2+ influx in adrenal chromaffin
      cells, suggesting that voltage-sensitive Ca2+ channels (VSCCs) are inhibited by
      protein kinase C-mediated phosphorylation. We now address the possibility that L-
      and P/Q-type Ca2+ channel subtypes might be differentially involved in phorbol
      ester action. In bovine chromaffin cells, short-term (10 min) incubations with
      phorbol 12-myristate 13-acetate (PMA) inhibited early high K+-evoked rises in
      cytosolic free Ca2+ concentration ([Ca2+]i) and the early component of the
      depolarization-evoked Mn2+ quenching of fura-2 fluorescence in a dose-dependent
      manner (IC50: 18 and 7 nM; maximal inhibitions: 45 and 48%, respectively). The
      protein kinase C inhibitor staurosporine (100 nM) reverted the inhibitory action
      of PMA. PMA (0.1-1 microM) inhibited the early and late phases of the ionomycin
      (2 microM)-evoked [Ca2+]i transients by 14-23%. Omega-agatoxin IVA, a blocker of
      P/Q-type Ca2+ channels, inhibited high K+-evoked [Ca2+]i rises in a dose
      dependent fashion (IC50 = 50 nM). In contrast, 0.1 microM omega-conotoxin GVIA, a
      blocker of N-type channels, was without effect. A sizeable (< 45%) component of
      early Ca2+ influx persisted in the combined presence of omega-agatoxin IVA (100
      nM) and nitrendipine (1 microM). Simultaneous exposure to omega-agatoxin IVA and
      PMA inhibited both the early [Ca2+]i transients and Mn2+ quenching to a much
      greater extent than each drug separately. Inhibition of the [Ca2+]i transients by
      nitrendipine and PMA did not significantly exceed that produced by PMA alone. It
      is concluded that phorbol ester-mediated activation of protein kinase C inhibits
      preferentially L-type VSCCs over P/Q type channels in adrenal chromaffin cells.
      However, the possibility cannot be ruled out that dihydropyridine-resistant, non
      P/Q type channels might also be negatively regulated by protein kinase C. This
      may represent an important pathway for the specific control of VSCCs by protein
      kinase C-linked receptors, not only in paraneurones but presumably also in
      neurones and other excitable cells.

PMID- 10082211
TI  - Functional potencies of new antiparkinsonian drugs at recombinant human dopamine
      D1, D2 and D3 receptors.
AB  - We measured the affinities of bromocriptine, pramipexole, pergolide and
      ropinirole at human recombinant dopamine D1, D2 and D3 receptors in binding and
      functional tests. All four compounds bound with high affinity at the dopamine D3
      receptor; bromocriptine and pergolide also had high affinity for the dopamine D2
      receptor, while only pergolide had significant, although moderate, affinity for
      the dopamine D1 receptor. Only pergolide had high potency and intrinsic activity
      at the dopamine D1 receptor for stimulating cyclic AMP accumulation. In addition,
      the potencies and efficacies of pergolide and bromocriptine, as well as that of
      dopamine, at the dopamine D1 receptor were increased in the presence of
      forskolin, an adenylate cyclase activator. All four compounds were highly potent
      agonists at dopamine D2 and D3 receptors, as measured in a mitogenesis assay.
      Bromocriptine was ten times more potent and pramipexole and ropinirole ten times
      less potent at the dopamine D2 than at the dopamine D3 receptor, whereas
      pergolide was equipotent at the two receptors. These results suggest that the
      activity of recently developed antiparkinsonian drugs at either the dopamine D1
      or the dopamine D3 and not only the dopamine D2 receptors should be taken into
      account in analyses of their mechanisms of action in therapeutics.

PMID- 10082212
TI  - Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology
      of the human alpha7V274T variant.
AB  - In the human alpha7 nicotinic receptor, valine-274 in the pore-lining
      transmembrane-2 region was mutated to threonine to produce the variant human
      alpha7V274T, which was evaluated electrophysiologically following expression in
      Xenopus laevis oocytes. Inward current rectification was strong in human
      alpha7V274T as in the human alpha7 wild type nicotinic receptor. However, human
      alpha7V274T was 100-fold more sensitive to the nicotinic receptor agonists
      acetylcholine, (-)-nicotine and 1,1-dimethyl-4-phenylpiperazinium. Choline also
      activated human alpha7V274T (EC50 = 12 microM) and was 82-fold more potent than
      at human alpha7 wild type nicotinic receptor. (-)-Cotinine, (2,4)
      dimethoxybenzylidene anabaseine (GTS-21) and 2-methyl-3-(2-(S)
      pyrrolidinylmethoxy)pyridine (ABT-089), weak partial agonists at human alpha7
      wild type, were much stronger agonists at human alpha7V274T with EC50 values of
      70 microM, 4 microM and 28 microM and fractional activation values of 93%, 96%
      and 40%, respectively. However, (-)-lobeline, a human alpha7 wild type nicotinic
      receptor antagonist, and dihydro-beta-erythroidine, which activates chick
      mutagenized alpha7 nicotinic receptors, had only weak agonist-like activity at
      human alpha7V274T (< or = 4% of the maximal acetylcholine response).
      Methyllycaconitine, mecamylamine, d-tubocurarine and dihydro-beta-erythroidine
      retained antagonist activity and, indeed, appeared to be at least as potent at
      human alpha7V274T as at human alpha7 wild type. These results support and extend
      the concept that human nicotinic receptor pharmacology can be profoundly altered
      by single amino acid changes in the pore-lining segment.

PMID- 10082213
TI  - Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic
      Ca2+.
AB  - Dotarizine (a novel piperazine derivative with antimigraine properties) and
      flunarizine (a Ca2+ channel antagonist) were compared concerning: first, their
      ability to cause chromaffin cell damage in vitro; second, the possible
      correlation of their octanol/water partition coefficients and those of another 28
      compounds (i.e., Ca2+ channel antagonists, blockers of histamine H1 receptors,
      antimycotics, beta-adrenoceptor antagonists, neuroleptics), with their ability to
      cause cell damage; third, their capacity to protect the cells against the
      damaging effects of veratridine; and fourth, their capabilities to enhance the
      basal cytosolic Ca2+ concentration in fura-2-loaded single chromaffin cells, or
      to modify the pattern of [Ca2+]i oscillations elicited by veratridine. After 24-h
      exposure to 1-30 microM dotarizine, the viability of bovine adrenal chromaffin
      cells (measured under phase contrast or as lactate dehydrogenase, released into
      the medium) was similar to that of control, untreated cells; at 100 microM, 80%
      lactate dehydrogenase release was produced. At 1-3 microM flunarizine caused no
      cell damage; however 10 microM caused 20% lactate dehydrogenase release and 30
      and 100 microM over 90% lactate dehydrogenase release. The time course of cell
      damage was considerably faster for flunarizine, in comparison to dotarizine. Out
      of 30 molecules tested (at 10 microM), having different octanol/water partition
      coefficients (log P), dotarizine was among the molecules causing no cell damage;
      flunarizine caused 20% cell loss, lidoflazine and verapamil over 50% cell loss,
      and penfluridol, draflazine, astemizole or nifedipine over 80% cell loss. No
      correlation was found between log P and cytotoxicity. Both dotarizine (10-30
      microM) and flunarizine (3-10 microM) provided protection against veratridine
      induced cell death; however, at 30 microM dotarizine afforded a pronounced
      protection while flunarizine enhanced the cytotoxic effects of veratridine.
      Dotarizine (30 microM) (but not flunarizine) caused a prompt transient elevation
      of the basal [Ca2+]i. Both compounds abolished the K+-induced increases of
      [Ca2+]i as well as the oscillations of [Ca2+]i induced by veratridine. The
      blocking effects of dotarizine were readily reversed after washout, while those
      of flunarizine were long-lasting. These differences might be relevant to the
      clinical use of dotarizine as an antimigraine drug.

PMID- 10082214
TI  - Development of an inducible NMDA receptor stable cell line with an intracellular
      Ca2+ reporter.
AB  - Cytotoxicity associated with NMDA receptor activation has impeded the
      establishment of cell lines expressing recombinant subtypes of this ligand-gated
      ion channel class. To circumvent this toxicity, we describe in this report the
      use of a potent inducible promoter in the construction of a cell line stably
      expressing the NR1a/NR2A subtype of the NMDA receptor. Western blot analysis
      using subunit selective antibodies revealed that NR2A subunits were
      constitutively expressed in this cell line, whereas expression of NR1a subunits
      was tightly regulated by tetracycline. Upon tetracycline removal,
      electrophysiological recordings using the patch clamp technique indicated the
      expression of functional receptors with biophysical and pharmacological
      properties corresponding to those expected of the NR1a/NR2A subtype. In addition,
      we utilized this cell line with the recombinant membrane targeted Ca2+ reporter,
      aequorin, in a functional assay of NMDA receptor activation. An evaluation of the
      coupling efficiency of NMDA receptor activation and aequorin response, as well as
      the pharmacological profile of this assay, illustrates the suitability of this
      cell line and the Ca2+ reporter assay to functionally identify novel NMDA
      receptor antagonists.

PMID- 10082215
TI  - [3H]GBR 12935 binding in platelets from poor and extensive cytochrome P-4502D6
      metabolizers.
AB  - Previous studies have indicated that part of the binding of [3H] [1-[2
      (diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR
      12935) to human platelets is to a piperazine acceptor site, which might be
      associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due
      to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of
      CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present
      study, possible differences in binding characteristics of [3H]GBR 12935 in
      platelets from CYP4502D6 poor and extensive metabolizers were investigated. The
      most prominent finding was a gender difference, with males having significantly
      higher Kd values than females. There were no differences in Bmax. After
      correction for gender, there was a tendency towards higher Kd values in poor
      metabolizers than in extensive metabolizers, although the difference was not
      statistically significant. Whether this finding corresponds to reduced CYP4502D6
      activity is a matter of further investigation.

PMID- 10082216
TI  - Trichloroethanol impairs NMDA receptor function in rat mesencephalic and cortical
      neurones.
AB  - The effects of 2,2,2-trichloroethanol, the active compound of the sedative
      hypnotic chloral hydrate, were investigated on N-methyl-D-aspartate (NMDA)
      induced increases in intracellular Ca2+ concentration ([Ca2+]i) in cultured
      mesencephalic and cortical neurones by means of the fura-2 method.
      Trichloroethanol inhibited the NMDA response in a concentration-dependent manner
      in cortical (IC50 = 2.76 mM) and mesencephalic neurones (IC50 = 1.12 mM), with a
      maximum effect of approximately 85 and 94%, respectively. Ethanol was
      considerably less potent than trichloroethanol. In conclusion, the
      trichloroethanol-induced impairment of NMDA receptor function may contribute to
      the sedative-hypnotic properties of chloral hydrate.

PMID- 10082217
TI  - Visceral chemical nociception in mice lacking mu-opioid receptors: effects of
      morphine, SNC80 and U-50,488.
AB  - Writhing responses to intraperitoneal acetic acid administration and their
      modulation by mu-, kappa- and delta-opioid receptor agonists were compared in
      wild-type and mu-opioid receptor knockout mice. Unpretreated homozygous knockout
      mice displayed less writhing than wild-type mice. U-50,488 [trans-3,4-dichloro-N
      methyl-N-[2-(1-pyrolidinyl)cyclohexyl]-benze neacetamide]) reduced writhing
      responses in wild-type and knockouts. Morphine and SNC80 [(+)-4-[9-alpha-R)-alpha
      (2S,5RO-4-allyl-2,5-dimethyl-1-piperaziny l)-3-methoxybenzyl]-N,N
      diethylbenzamide] were effective in wild-type mice but ineffective in knockouts.
      Mu-opioid receptors appear to play important roles in responses to this visceral
      nociceptive stimulus and its modulation by mu- and delta-opioid receptor
      agonists.

PMID- 10082218
TI  - [D-Ala2, D-Leu5]enkephalin blocks the methamphetamine-induced c-fos mRNA increase
      in mouse striatum.
AB  - The administration of methamphetamine caused an increase of c-fos mRNA in the
      striatum of the mouse. A systemic injection of the delta-opioid receptor agonist,
      [D-Ala2, D-Leu5]enkephalin (DADLE), attenuated the c-fos mRNA increase induced by
      methamphetamine. These results suggest that endogenous delta-opioid peptides
      might counteract certain genomic influences exerted by psychostimulants such as
      methamphetamine.

PMID- 10082219
TI  - Endothelium is involved in the vasorelaxation by an ATP-sensitive K+ channel
      opener, NIP-121.
AB  - Possible involvement of endothelium was examined in the vasorelaxation of rat
      aorta in response to NIP-121 ((+)-7,8-dihydro-6,6-dimethyl-7-hyroxy-8-(2-oxo-1
      piperidinyl)-6H- pyrano[2,3-f]benz-2,1,3-oxadiazole), an ATP-sensitive K+
      (K(ATP)) channel opener. The NIP-121-induced vasorelaxation was greater in
      endothelium-intact preparations than in endothelium-denuded ones. In the presence
      of glibenclamide, which inhibits K(ATP) channels, NIP-121-induced vasorelaxations
      were of a similar extent in both endothelium-intact and -denuded preparations.
      These findings suggest that the presence of endothelium plays a role in the
      vasorelaxation in response to K(ATP) channel openers.

PMID- 10082220
TI  - Clozapine potently stimulates mesocortical dopamine neurons.
AB  - The effects of clozapine on dopamine neurons projecting to the medial-prefrontal
      cortex, nuclei accumbens and caudatus were compared. Clozapine (1.25 mg/kg i.v.)
      maximally stimulated the firing rate and burst activity of dopamine neurons
      projecting to the medialprefrontal cortex. Much higher doses (5 and 10 mg/kg
      i.v.) were needed to stimulate mesoaccumbens and nigrostriatal dopamine neurons.
      The results suggest that the activation of mesocortical dopamine neurons is
      responsible for clozapine-induced dopamine release in the prefrontal cortex.

PMID- 10082221
TI  - Effects of D1 and D2 dopamine receptor antagonists on cocaine-induced self
      stimulation and locomotor activity in rats.
AB  - To clarify the involvement of D1 and D2 dopamine systems in intracranial self
      stimulation (ICSS) and locomotor activity in rats, we studied the acute effects
      of cocaine and the interaction between cocaine and dopamine antagonists with
      respect to these behaviors. Although cocaine (5.0, 10.0, or 20.0 mg/kg) dose
      dependently increased locomotor activity, it augmented the rate of ICSS only at
      5.0 mg/kg. The failure of high doses of cocaine to augment purpose-oriented
      behavior such as ICSS may result from its induction of a manic-like state. The D1
      dopamine receptor antagonist SCH23390 (0.02, 0.1, or 0.5 mg/kg) or the D2
      antagonist nemonapride (0.04, 0.2, or 1.0 mg/kg) significantly decreased cocaine
      augmentation of ICSS. The higher two doses of either antagonist also produced a
      significant decrease in cocaine-induced locomotor activity. We therefore suspect
      that cocaine's augmentative effect on those behaviors, especially ICSS, requires
      activation of both D1 and D2 dopamine receptors.

PMID- 10082222
TI  - Effects of CCK antagonists on GABA mechanism-induced antinociception in the
      formalin test.
AB  - In this work, the influences of CCK receptor antagonists on antinociception
      induced by the GABA receptor agonist, baclofen, and the GABA uptake inhibitor,
      THPO, in the formalin test have been studied. GABA-B agonist baclofen (0.75, 1.25
      and 2.5 mg/kg), THPO, a GABA uptake inhibitor (1 and 2 mg/kg) and morphine (1.5,
      3 and 6 mg/kg) induced antinociception in both phases of the formalin test in
      mice. The selective CCK receptor antagonists, L-365,260, MK-329 (0.05, 0.125 and
      0.25 mg/kg) and non-selective CCK receptor antagonist, proglumide (2.5, 5, 10 and
      20 mg/kg) induced antinociception only in high doses. The CCK receptor
      antagonists potentiated baclofen (0.75, 1.25 and 2.5 mg/kg) or THPO (1 and 2
      mg/kg) responses. It may be concluded that the CCK receptor mechanism may
      interact with GABA-function in its antinociceptive effect.

PMID- 10082223
TI  - In vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, WAY
      100,635 and (S)-(-)-UH-301 at rat brain monoamine receptors.
AB  - The receptor-mediated control of brain monoamine synthesis was used to examine
      the in vivo intrinsic efficacy of the 5-HT1A receptor antagonists NAD-299, S(-)
      UH-301 and WAY-100,635. The rate of monoamine synthesis was estimated by
      measuring the accumulation of DOPA and 5-HTP in the ventral neostriatum and the
      ventral hippocampus in rats pretreated with an inhibitor of cerebral aromatic L
      amino acid decarboxylase. S(-)-UH-301 (2.0-32.0 micromol kg(-1)), but not WAY
      100,635 (0.08-1.2 micromol kg(-1)), produced a decreased 5-HTP accumulation in
      the neostriatum and in the hippocampus. The administration of NAD-299 (0.75-12.0
      micromol kg(-1)) resulted in a slight increase in neostriatal, but not
      hippocampal, 5-HTP accumulation. Neostriatal DOPA accumulation was decreased by
      S(-)-UH-301, whereas treatment with WAY- 100,635 resulted in an increase. NAD-299
      did not affect neostriatal DOPA levels. There were no effects by any of these
      agents on DOPA levels in the ventral hippocampus. It is concluded that S(-)-UH
      301, but not WAY-100,635 or NAD-299, displays intrinsic efficacy at brain 5-HT1A
      and DA D2/3 receptors, whereas WAY-100,635 behaves as a DA D2/3 receptor
      antagonist. By this comparison, NAD-299 appears to be the most selective and
      specific 5-HT1A receptor antagonist.

PMID- 10082224
TI  - (+)-S-20499 -- a potential antidepressant? A behavioural and neurochemical
      investigation in the olfactory bulbectomised rat.
AB  - The study was designed to assess the potential antidepressant properties of the 5
      HT1A receptor agonist, (+)-S-20499 (10 mg kg(-1) i.p.) in the olfactory
      bulbectomised (OB) rat. Following 2 weeks of treatment, the rats were tested in
      the elevated plus maze and the "open field". A characteristic hyperactive
      response was evident in the OB animals in the "open field" which was reversed
      following chronic treatment with (+)-S-20499. In the elevated plus maze an
      increase in the number of open arm entries and the time spent on the open arms
      was observed, although this failed to reach significance. A significant decrease
      in beta1 receptor affinity was evident following olfactory bulbectomy which was
      normalised by (+)-S-20499. (+)-S-20499 also significantly reduced the density of
      5-HT2 receptors in the sham operated (SO) animals. These studies demonstrate the
      usefulness of the OB rat as a screening test for compounds with novel putative
      mechanisms of action, and highlights the potential antidepressant properties of
      (+)-S-20499.

PMID- 10082225
TI  - The effects of benzodiazepine (triazolam), cyclopyrrolone (zopiclone) and
      imidazopyridine (zolpidem) hypnotics on the frequency of hippocampal theta
      activity and sleep structure in rats.
AB  - In order to investigate the relative efficacy and safety of zopiclone and
      zolpidem, we compared the effects of higher doses of zopiclone and zolpidem on
      the frequency of hippocampal theta activity and sleep structure with that of
      triazolam. Rats were divided into triazolam treatment group (1 mg/kg, 5 mg/kg),
      zopiclone treatment group (20 mg/kg, 100 mg/kg) and zolpidem treatment group (20
      mg/kg, 100 mg/kg). Rats were injected intraperitoneally with these drugs or their
      vehicle. Polygraphic sleep recording and visual frequency analysis of the
      hippocampal EEG activity in REM sleep were carried out for 6 h after each
      injection. Zolpidem, unlike triazolam and zopiclone, had a much milder reducing
      effect on the frequency of hippocampal theta activity and suppressing-effect on
      REM sleep. These results suggest that zolpidem may prove to be a safer hypnotic
      drug which has fewer or milder side effects than are benzodiazepine and
      cyclopyrrolone hypnotics.

PMID- 10082226
TI  - Cholecystokinin receptor agonists block the jumping behaviour precipitated in
      morphine-dependent mice by naloxone.
AB  - The aim of present study was to reveal the role of cholecystokinin (CCK) in the
      jumping behaviour induced by the opioid antagonist naloxone (30 mg/kg) after the
      acute administration of morphine (200 mg/kg) in mice. Treatment with caerulein
      (0.01-1 microg/kg), a nonselective agonist of CCK receptors, induced a large
      reduction of jumping frequency without parallel suppression of locomotor
      activity. The CCK(B) receptor agonist CCK tetrapeptide (CCK-4. 0.125-32 mg/kg)
      caused the same effect, but it happened at much higher doses (above 0.5 mg/kg).
      Devazepide (1 microg/kg), a preferential CCK(A) receptor antagonist, completely
      reversed the action of caerulein (0.1 gmg/kg) and CCK-4 (2 mg/kg). A preferential
      CCK(B) receptor antagonists LY 288,513 at a high dose (4 mg/kg) blocked the
      action of CCK-4, but not that of caerulein. Acetorphan (16-128 mg/kg), an
      inhibitor of enkephalin metabolism, did not block naloxone-precipitated jumping
      behaviour. However, the combination of subthreshold doses of caerulein (0.001
      microg/kg) and CCK-4 (0.25 mg/kg) with acetorphan (64 mg/kg) potently antagonized
      the behaviour induced by naloxone. In conclusion, the antagonism of CCK agonists
      against naloxone-precipitated jumping behaviour is apparently mediated via the
      CCK(A) receptor subtype. The stimulation of CCK(A) receptors seems to increase
      the release of endogenous enkephalins.

PMID- 10082227
TI  - The effects of flumazenil on two way active avoidance and locomotor activity in
      diazepam-treated rats.
AB  - The present study was undertaken to determine the effects of chronic flumazenil
      treatment alone and simultaneously with diazepam on acquisition performance in an
      active-avoidance task and on locomotor activity in rats. Flumazenil (5, 10 and 20
      mg/kg) and diazepam (0,5, 1.0 and 2.0 mg/kg) were administered intraperitoneally
      to rats before each daily training session for 5 days. The baseline of avoidance
      performance was set to approximately 50% and responses were expressed as
      acquisition rate. Locomotor activity of the rats was simultaneously recorded but
      only following the first training session. Diazepam decreased acquisition rate
      between the dose range used. Flumazenil had no effect on the acquisition rate of
      naive rats but reversed low dose diazepam-induced learning and memory impairment.
      Diazepam induced locomotor depression within the same dose range that decreased
      acquisition rate. Flumazenil had no effect on locomotor activity, but reversed
      the locomotor depressant effect of diazepam. The striking contradiction with
      previous data that flumazenil has no effect on learning-memory processing is
      discussed.

PMID- 10082228
TI  - Effects of acute or long-term treatment with chlorpromazine, haloperidol or
      sulpiride on neuropeptide Y-like immunoreactivity concentrations in the nucleus
      accumbens of rat.
AB  - The effects of acute, subchronic ( 14 days) or chronic (28 days) intraperitoneal
      (i.p.) administration of chlorpromazine (2 or 10 mg/kg), haloperidol (0.5 or 2
      mg/kg) or sulpiride (50 or 100 mg/kg) on the neuropeptide Y (NPY) system in the
      rat nucleus accumbens were studied. NPY-like immunoreactivity (NPY-LI) decreased
      in a dose- and time-dependent manner, and was the lowest after haloperidol. NPY
      LI levels increased 8 days after withdrawal of chronic drugs treatment. Acute
      administration of haloperidol reduced NPY mRNA, while Subchronic treatment did
      not change it. Subchronic i.p. administration of the dopamine D1-like antagonist
      SCH 23390 (1 mg/kg) reduced NPY-LI levels but the alpha1-adrenergic antagonist
      prazosin (0.2 mg/kg) had no effect. The effect of sulpiride coadministered with
      SCH 23390 was greater than that of SCH 23390 alone, while prazosin coadministered
      with sulpiride insignificantly reduced the effect of sulpiride. The dopamine
      D2/D3 agonist quinpirole given as a single injection (3 mg/kg) did not alter NPY
      LI content by itself but antagonized the chlorpromazine-induced decrease and
      attenuated the haloperidol-induced decrease. Our findings indicate that the
      accumbens NPY system is markedly affected by the antipsychotics studied, and
      suggest that their effects may be in part mediated by blockade of D2-like (D2,
      D3) and D1 dopaminergic receptors.

PMID- 10082229
TI  - The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate:
      a double blind study of alpha-methyl-para-tyrosine.
AB  - Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para
      tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a
      biological marker of catecholamine function since its secretion is regulated by
      noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten
      healthy volunteers were administered AMPT in a double-blind placebo controlled
      study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM)
      decreased significantly as compared with promethazine (night 1 P=0.002; and night
      2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82,
      GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly
      (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in
      symptomatology and did not correlate with changes in 6-SM or MHPG. This study
      demonstrates in healthy controls that 6-SM reliably reflects presynaptic
      catecholamine depletion induced by AMPT without the emergence of behavioral
      symptoms.

PMID- 10082230
TI  - Pituitary-adrenal reactivity in a child psychiatric population: salivary cortisol
      response to stressors.
AB  - The aim of this explorative study was to investigate whether physical and
      psychological challenges are effective in inducing a cortisol response in
      psychiatric and control children, and if so whether the cortisol response can
      discriminate between diagnostic groups and is related to psychiatric symptoms.
      Fifty-two patients, including children with dysthymia, oppositional defiant
      disorder/conduct disorder, pervasive developmental disorder, not otherwise
      specified (PDDNOS) and attention deficit hyperactivity disorder, were compared to
      15 healthy control children. Symptomatology was scored using the Child Behaviour
      Checklist. The response to both psychological and physical challenges was
      assessed by measuring salivary cortisol and heart rate. Physical challenge, but
      not psychological challenge, resulted in an overall increase in heart rate and
      saliva cortisol. Dysthymic and PDDNOS patients showed a diminished cortisol
      response, in spite of a significant increase in heart rate. These groups scored
      highest on the symptom factor withdrawal. Withdrawal was negatively correlated
      with the cortisol response. Thus, physical exercise is effective in inducing a
      salivary cortisol response in children. Dysthymic and PDDNOS patients have a
      disturbed pituitary-adrenal function in relation to physical stress, that may be
      associated with withdrawal.

PMID- 10082231
TI  - The use of a side effect as a qualitative indicator of plasma chlorpromazine
      levels.
AB  - Chlorpromazine (CPZ) is widely used in South African hospitals. The purpose of
      this study was to determine whether any physiological parameter (side-effect)
      could be correlated with plasma concentrations of CPZ or its metabolites. In the
      absence of a blood level, such a correlation could serve as a qualitative
      indicator of the amount of chlorpromazine in the body. Such a marker can assist
      the psychiatrist with therapeutic decisions regarding poor compliance and the
      lack of response with the drug. Fifteen schizophrenic patients were included in
      this study and regression analysis was used to determine any correlation between
      CPZ, 7-hydroxychlorpromazine, Chlorpromazine-N-oxide, Nor1 chlorpromazine, Nor2
      chlorpromazine, chlorpromazine sulfoxide, Nor2 chlorpromazine sulfoxide and blood
      pressure, pulse rate, sedation and finger tremor. No correlation was seen between
      blood pressure or pulse rate and plasma concentrations of CPZ or the metabolites.
      A good correlation was seen between sedation, 7- hydroxychlorpromazine (P=0.035)
      and chlorpromazine sulfoxide (P=0.016). The results suggest that as the levels of
      chlorpromazine sulfoxide increase, the probability of sedation increases, while
      increasing levels of 7-hydroxychlorpromazine have the opposite effect. A good
      correlation was also seen between finger tremor and chlorpromazine levels
      (P=0.035). These results suggest that there is a 50% probability that the patient
      would experience finger tremor when the plasma concentration of chlorpromazine is
      46 ng/ml. This study demonstrated the potential for the use of sedation and
      finger tremor as qualitative indicators of the plasma concentration of CPZ and
      two metabolites. Further studies with larger patient numbers are warranted.

PMID- 10082232
TI  - Treatment resistant depression: methodological overview and operational criteria.
AB  - A wide variety of definitions are used for Treatment Resistant Depression (TRD),
      considering various criteria and different concepts. Some of the key issues are:
      the diagnosis, the treatment adequacy in terms of dose and duration, the
      treatment response assessment and the number of failed therapeutic trials
      required. Systematic research has been characterizing the concept and criteria to
      define the different variables involved. Lack of consensus on these issues limits
      comparison across clinical trials and interpretation of treatment efficacy in the
      management of treatment resistant patients. Through reanalyzes of available data,
      we point out the limits of TRD definitions and propose conceptual and operational
      criteria for a collaborative research project on TRD. It appears that a number of
      variables commonly associated to treatment resistance are independent of patients
      characteristics and mainly refer to misdiagnosis and inadequate treatment. The
      proposed criteria are intended for therapeutic trials in TRD, combining the
      evaluation of treatment efficiency and the validation of the concept of TRD
      itself. Major depression with poor response to two adequate trials of different
      classes of antidepressants is proposed for an operational definition of TRD.
      Rationale for this definition is discussed in contrast to alternative
      definitions.

PMID- 10082233
TI  - Naltrexone affects cocaine self-administration in naive rats through the ventral
      tegmental area rather than dopaminergic target regions.
AB  - Behavioural studies have shown an involvement of central endogenous opioid
      systems in experimental cocaine addiction. Seeking to further localize the
      attenuating effect of opioid blockade on the reinforcing effects of cocaine,
      naltrexone was administered locally to different regions of the mesocorticolimbic
      system, which are thought to be critically involved in cocaine self
      administration behaviour. Both cell body and nerve terminal regions of this
      system were targeted. Using a model for the initiation of cocaine self
      administration behaviour, no effect of naltrexone was found in caudate,
      amygdaloid or accumbens nuclei, nor in the medial prefrontal cortex. However,
      blockade of endogenous opioid receptors in the ventral tegmental area region
      attenuated cocaine self-administration. With the initiation model, this finding
      reflects an attenuating effect on the reinforcing effects of cocaine. The
      attenuation of self-administration was dependent on the naltrexone dose. The
      present findings suggest that endogenous opioid systems in the ventral tegmental
      area modulate the reinforcing efficacy of cocaine.

PMID- 10082234
TI  - An investigation of the antidepressant properties of lofepramine and its
      desmethylated metabolites in the forced swim and olfactory bulbectomized rat
      models of depression.
AB  - The purpose of this study was to examine the metabolites of lofepramine (LOF),
      namely desipramine (DMI), desmethyl desipramine (DDMI) and desmethyl lofepramine
      (DML) in the forced swim and olfactory bulbectomized (OB) rat models of
      depression. In the first study, subacute treatment with DMI (10 mg/kg) and DML
      (20 mg/kg), but not LOF, reduced the immobility time in the forced swim test. In
      the "open field", chronic (14 day) treatment with all drugs attenuated the
      hyperactivity associated with olfactory bulbectomy. In the second experiment, a
      lower dose of DML (10 mg/kg) demonstrated activity following subacute treatment
      in the forced swim and following chronic treatment in the OB model. In addition,
      DDMI (10 mg/kg) was active in both models. From these results, it can be
      concluded that, at the doses employed, LOF and it's desmethylated metabolites,
      DMI, DML and DDMI, exhibits activity in the OB model. In contrast, lofepramine
      but not it's desmethylated derivatives is inactive in the forced swim test,
      perhaps suggesting the requirement of metabolic conversion of LOF to reveal
      antidepressant activity in this model.

PMID- 10082235
TI  - The platelet intracellular calcium response to serotonin and thrombin in patients
      with panic disorder.
AB  - Serotonin is implicated in both the biology of depression and anxiety. The aim of
      this study was to examine the platelet intracellular calcium response to
      serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic
      disorder compared to 14 matched controls. Patients did not show significantly
      higher baseline platelet intracellular calcium levels and serotonin stimulated
      levels of intracellular calcium than control subjects. There was a much smaller
      standard deviation in the control subjects than in the panic patients. The
      intracellular calcium response to thrombin activation was however greater in
      panic patients than in control subjects (P<0.001). The failure of this study to
      find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with
      the findings of previous challenge studies that found no consistent dysregulation
      of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless
      suggests some receptor mediated second messenger changes independent of serotonin
      in the disorder.

PMID- 10082236
TI  - Fluoxetine treatment for weight reduction in steroid-induced obesity: a pilot
      study in myasthenia gravis patients.
AB  - To evaluate the weight reducing effect of fluoxetine on steroid-induced obesity,
      we conducted an open, clinical intervention study of 20-40 mg/day fluoxetine, 24
      weeks duration. Thirteen myasthenia gravis, overweight, long-term steroid-treated
      patients [age: 31-59, body mass index (BMI): 29-54 kg/m2] were included.
      Measurements of weight, BMI, and routine laboratory tests, were undertaken at
      baseline, 12 and 24 weeks. Muscle strength and fatigue parameters were assessed
      at 4 week intervals. Fluoxetine induced mean weight loss of 7.7+/-2.6 kg and
      10.3+/-2.9 kg over a period of 12 and 24 weeks respectively, (P<0.05). Mean BMI
      decreased from 35.8 to 32.2 kg/m2 over the study period. No significant side
      effects were noted. We conclude that patients suffering from steroid-induced
      obesity respond to fluoxetine treatment of overweight by significant weight loss.

PMID- 10082237
TI  - Nitric oxide modulates spinal antinociceptive effect of clonidine but not that of
      baclofen in the formalin test in rats.
AB  - The aim of present study was to determine the influence of nitric oxide (NO)
      synthesis on intrathecal (i.t.) clonidine or baclofen antinociception in the
      formalin test. Formalin injection into the hindpaw of a rat induces a biphasic
      response in pain-related behaviours, such that C-fiber activation (acute pain)
      during phase 1 triggers a state of spinal sensitization characterized by longer
      lasting phase 2 (tonic pain). Intrathecal clonidine and baclofen, at doses
      without effect upon motor performance, produced a dose-dependent inhibition of
      both phases of the formalin test. Potency of both drugs, defined by ID50 for
      phase 2 of the formalin test, was 3.5 and 0.6 nmol, respectively. Intrathecal
      coadministration of L-arginine, substrate of NO synthase (NOS) or NOS inhibitor,
      N(G)-nitro-L-arginine methyl ester (L-NAME), dose-dependently reduced or
      potentiated, respectively, the antinociceptive effect of clonidine but not that
      of baclofen in the formalin test. The importance of NO formation in the
      antinociceptive effect of clonidine is further supported by the observation that
      neither D-arginine nor D-NAME were able to modify clonidine antinociception.
      These results suggest that the NO synthesis plays a modulatory role in the
      antinociceptive effect of clonidine, while the mechanism underlying the baclofen
      induced antinociception seems to be different.

PMID- 10082238
TI  - A comparison of the effects of different serotonin reuptake blockers on sexual
      behaviour of the male rat.
AB  - In human males, SSRIs differentially affect (premature) ejaculation; paroxetine
      and fluoxetine markedly and sertraline, moderately inhibited ejaculation latency,
      whereas fluvoxamine did not inhibit this parameter (Waldinger, M.D., Hengeveld,
      M.W., Zwinderman, A.H., Olivier, B., The effect of SSRI antidepressants on
      ejaculation: a double-blind, randomised, placebo-controlled study with
      fluoxetine, fluvoxamine, paroxetine and sertraline. J. Clin. Psychopharmacol. (in
      press)). The present studies tried to investigate, using sexual behaviour in male
      rats, whether such differences could also be found in animal paradigms of sexual
      behaviour. In a series of three experiments we compared various specific
      serotonin reuptake inhibitors (SSRIs) for their ability to suppress sexual
      behaviour in male rats. In the first experiment sexually experienced rats were
      tested 60 min after oral administration of clomipramine, fluvoxamine, fluoxetine
      (all in a range of 0, 3, 10 and 30 mg/kg p.o.), sertraline or paroxetine (both in
      a range of 0, 1, 3 and 10 mg/kg p.o.). Clomipramine, paroxetine and fluvoxamine
      did not significantly inhibit male sexual behaviour, although some trends were
      observed. Sertraline inhibited sexual behaviour at 3 and 10 mg/kg p.o., the
      effects being stronger at 3 mg/kg p.o. Fluoxetine (3 mg/kg p.o.) facilitated
      sexual behaviour, while at 30 mg/kg p.o. a modest increase in the postejaculatory
      interval was noted. In the second experiment, sexual behaviour of sexually naive
      male rats was slightly inhibited by paroxetine 10 mg/kg p.o., but sertraline
      (range 1-10 mg/kg p.o.), fluvoxamine and fluoxetine (both in a range of 3-30
      mg/kg p.o.) were ineffective. In the last experiment the effects of paroxetine (0
      10 mg/kg p.o.), fluvoxamine and fluoxetine (both 0-30 mg/kg p.o.) were studied
      during an exhaustion design in sexually experienced male rats. As rats get more
      'sluggish' when they have had multiple ejaculations, we hoped to see stronger
      inhibitory effects in the last cycle prior to exhaustion. None of the drugs dose
      dependently inhibited the pattern of sexual behaviour during the first sexual
      cycle. In the last cycle the patterning of sexual behaviour differed, but only
      paroxetine (10 mg/kg p.o.) inhibited sexual behaviour significantly. The total
      number' of ejaculations during the test was not reduced by any of the SSRIs
      tested. Contrary to human findings, we did not find major inhibitory effects of
      SSRIs on male rat sexual behaviour at non-sedative doses. The only
      differentiation that could be made is that paroxetine and sertraline had slightly
      stronger effects than the other 5-HT reuptake inhibitors. Masculine sexual
      behaviour in rats does not constitute a suitable model to investigate the
      differential mechanism of sexual inhibition of SSRIs that have been described in
      human males.

PMID- 10082239
TI  - Risperidone-induced rabbit syndrome: an unusual movement disorder caused by an
      atypical antipsychotic.
AB  - Rabbit syndrome is a rare side effect of chronic neuroleptic administration
      characterized by rapid, fine, rhythmic movements of the mouth along a vertical
      axis. It gains its name from an unusual resemblance to the chewing and puckering
      motions of the rabbit. It is generally thought to be an extra-pyramidal side
      effect, in part due to its rapid response to anti-cholinergic medication. This is
      the first case report of risperidone, an atypical antipsychotic, inducing the
      syndrome. The theoretical implications for the classification of the syndrome
      along the spectrum of neuroleptic-induced movement disorders are discussed.

PMID- 10082240
TI  - Plasma monoamine metabolites and aggression: two studies of normal and
      oppositional defiant disorder children.
AB  - In two studies the relationship between plasma monoamine metabolites and
      different parameters of aggression were examined in children suffering from
      severe aggression and antisocial behavior. No prior studies have related measures
      of serotonergic function to experimentally elicited aggression and only a few
      included healthy comparison groups. Plasma 5-HIAA, HVA and MHPG were measured in
      15 boys with a oppositional defiant disorder (ODD) and 25 normal controls (NC)
      (study 1), and 22 ODD and 25 NC children (study 2). On a separate occasion each
      subject had the opportunity to behave aggressively towards an opponent. 5-HIAA
      and HVA were significantly lower in the ODD than NC group and both parameters
      were significantly inversely correlated with aggression and delinquency. These
      findings were replicated in the second study: The results of the study support a
      role for serotonergic functioning in persistent antisocial and aggressive
      behavior in young children.

PMID- 10082241
TI  - CCK4-induced panic in healthy subjects I: psychological and cardiovascular
      effects.
AB  - Sixteen healthy subjects participated in a crossover, double blind, and placebo
      controlled study, designed to assess simultaneously the psychological and
      cardiovascular effects of cholecystokinin tetrapeptide (CCK4). Following an i.v.
      injection of 25 microg of CCK4, 44 percent of subjects experienced symptoms that
      fulfilled the DSM-IV criteria for a panic attack while no one panicked with
      placebo. CCK4 induced a significantly greater number and higher intensity of
      panic-like symptoms than placebo. A significant increase in state anxiety was
      observed in the period after CCK4 injection; this increase was significantly
      larger than the non-specific anxious reaction to placebo. CCK4 also affected
      cardiovascular signs. Both heart rate and mean blood pressure significantly
      increased after administration of CCK4. Again, these increases were significantly
      higher than those seen after placebo injection. We conclude that, in healthy
      subjects, CCK4 induces panic-like reaction characterized by a number of somatic,
      cognitive and emotional symptoms, which are accompanied by increases in heart
      rate and blood pressure.

PMID- 10082242
TI  - CCK4-induced panic in healthy subjects II: neurochemical correlates.
AB  - Cholecystokinin tetrapeptide (CCK4) induces symptoms similar to those of panic
      attack. The present study investigated the effects of CCK4 administration on
      catecholaminergic system. In this double blind, randomised, crossover experiment,
      16 healthy subjects received injections of either 25 microg of CCK4 or placebo on
      two separate occasions. Platelet and plasma catecholamine concentrations were
      assessed before the administration and compared to post-injection values. The
      results clearly show that both plasma and platelet concentrations of
      catecholamines are significantly affected by CCK4. Plasma norepinephrine (NE) and
      epinephrine (EPI) raised significantly above baseline in the immediate post-CCK4
      period, while in plasma dopamine (DA), the significant increases were delayed. In
      the platelets, significant post-CCK4 increases of NE and EPI concentrations were
      observed with a delay of several minutes. In summary, we have demonstrated that,
      in healthy subjects, CCK4 increases peripheral concentrations of catecholamines
      in both plasma and platelets, with the most consistent changes occurring in
      platelet NE and plasma EPI concentrations.

PMID- 10082243
TI  - Effects of acute and chronic antidepressant administration on phencyclidine (PCP)
      induced locomotor hyperactivity.
AB  - Previously it was found that both acute and chronic antidepressant pre-treatment
      enhanced the locomotor hyperactivity induced by a challenge injection of the non
      competitive NMDA receptor antagonist, dizocilpine (MK-801). In the present study
      the effects of acute and chronic antidepressant administration on phencyclidine
      (PCP)-induced locomotor hyperactivity were examined. Phencyclidine (PCP), a non
      competitive NMDA receptor antagonist increased locomotor activity in rats.
      Fluoxetine given acutely increased and prolonged the PCP-induced locomotor
      hyperactivity, while citalopram, sertraline and paroxetine had no effect on the
      PCP-induced behavioural effect. Repeated treatment with fluoxetine, citalopram
      and paroxetine increased the PCP-induced locomotor hyperactivity. In contrast,
      chronic sertraline administration attenuated the locomotor response to a PCP
      challenge. These results indicate that these antidepressants which are presumed
      to have a similar pharmacological profile, differ in their ability to alter PCP
      induced hyperactivity. Whether these differences have any bearing on the
      therapeutic or adverse effects of these drugs remains to be shown.

PMID- 10082244
TI  - Effects of (+/-)-kavain on voltage-activated inward currents of dorsal root
      ganglion cells from neonatal rats.
AB  - Kava pyrones extracted from pepper Piper methysticum are pharmacologically active
      compounds. Since kava pyrones exhibit anticonvulsive, analgesic and centrally
      muscle relaxing properties, the influence of a synthetic kava pyrone, (+/-)
      kavain, on voltage-dependent ion channel currents was studied. Effects of (+/-)
      kavain on voltage-activated inward currents were analysed in cultured dorsal root
      ganglion cells derived from neonatal rats. Voltage-activated Ca2+ and Na+
      currents were elicited in the whole-cell configuration of the patch clamp
      technique. Extracellularly applied (+/-)-kavain dissolved in hydrous salt
      solutions reduced voltage-activated Ca2+ and Na+ channel currents within 3-5 min.
      As the solubility of (+/-)-kavain in hydrous solutions is low, dimethyl sulfoxide
      (DMSO) was added to the saline as a solvent for the drug in most experiments.
      When (+/-)-kavain was dissolved in DMSO, the drug induced a fast and pronounced
      reduction of both Ca2+ and Na+ currents, which partly recovered within 2-5 min
      even in the presence of the drug. The present study indicates that (+/-)-kavain
      reduces currents through voltage-activated Na+ and Ca2+ channels.

PMID- 10082245
TI  - In vivo visualization of serotonin transporters in the human brain during
      fluoxetine treatment.
AB  - Beta-CIT can be used as a tracer for SPECT to visualize serotonin transporters in
      the human brain. We present a case of bulimia nervosa and major depressive
      disorder, who had been treated with up to 60 mg/d fluoxetine for several weeks.
      Four hours after injection of the tracer more than 40% of serotonin transporters
      were blocked. To our knowledge, this is the first direct documentation of the
      pharmacodynamic action of fluoxetine in the human brain in vivo.

PMID- 10082246
TI  - The International Child Neurology Association: the first 25 years.

PMID- 10082247
TI  - Neuron-specific enolase levels in the cerebrospinal fluid of neurologically
      healthy children.
AB  - Levels of neuron-specific enolase (NSE) levels in the cerebrospinal fluid (CSF)
      of children without neurological disease were assessed. CSF samples were obtained
      from 37 subjects aged between 1 month and 13 years. All subjects had undergone
      lumbar puncture for diagnostic purposes, and were subsequently shown not to be
      suffering any form of neurological disease. NSE levels in CSF were determined by
      an enzyme immunoassay method. NSE level ranged from below the detection limit to
      4.8 ng/ml (1.52+/-1.01 ng/ml). The present results may be useful as a basis for
      defining reference levels of NSE in CSF in post-neonatal children.

PMID- 10082248
TI  - Infantile spasm: the effect of corticotropin (ACTH) on the free amino acid
      profile in cerebrospinal fluid.
AB  - Increased excitatory amino acid neurotransmission has been implicated in the
      pathogenesis of infantile spasm. In this study we studied the profile of free
      amino acids in cerebrospinal fluid (CSF) from 16 patients with infantile spasm
      before corticotropin (ACTH) treatment. After 10 weeks ACTH therapy the profile of
      amino acids in CSF was studied once more in eight of the patients. Eleven
      patients were in the symptomatic group, and five in the cryptogenic group.
      Increased aspartate levels were measured in CSF following ACTH therapy (P<0.05).
      It was concluded that aspartate might have an important role in hypothalamic
      hypophyseal axis in patients with infantile spasm.

PMID- 10082249
TI  - 18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in type IV 3
      methylglutaconic aciduria: clinical and MRI correlations.
AB  - The clinical, 18fluorodeoxyglucose positron emission tomography (18FDG PET) and
      the magnetic resonance imaging (MRI) brain scan characteristics of four patients
      diagnosed to have 3-methylglutaconic aciduria were reviewed retrospectively. The
      disease has a characteristic clinical pattern. The initial presentations were
      developmental delay, hypotonia, and severe failure to thrive. Later, progressive
      encephalopathy with rigidity and quadriparesis were observed, followed by severe
      dystonia and choreoathetosis. Finally, the patients became severely demented and
      bedridden. The 18FDG PET scans showed progressive disease, explaining the
      neurological status. It could be classified into three stages. Stage I: absent
      18FDG uptake in the heads of the caudate, mild decreased thalamic and cerebellar
      metabolism. Stage II: absent uptake in the anterior half and posterior quarter of
      the putamina, mild-moderate decreased uptake in the cerebral cortex more
      prominently in the parieto-temporal lobes. Progressive decreased thalamic and
      cerebellar uptake. Stage III: absent uptake in the putamina and severe decreased
      cortical uptake consistent with brain atrophy and further decrease uptake in the
      cerebellum. The presence of both structural and functional changes in the brain,
      demonstrated by the combined use of MRI and 18FDG PET scan, with good clinical
      correlation, make the two techniques complementary in the imaging evaluation of 3
      methylglutaconic aciduria.

PMID- 10082250
TI  - Developmental expression of monocyte chemoattractant protein-1 in the human
      cerebellum and brainstem.
AB  - The developmental expression of monocyte chemoattractant protein-1 (MCP-1) in the
      cerebellum, medulla oblongata and pons was investigated in 26 normal human
      brains, ranging from 20 weeks of gestation (GW) to adulthood by means of an
      immunohistochemical method. Immunoreactivity to MCP-1 was observed in neurons of
      the cerebellum and brainstem, and was mainly distributed in the cytoplasm and
      dendrites. MCP-1-positive Purkinje cells appeared at 27 GW, reached a peak at 36
      GW, and then decreased after 1 month of age, almost completely disappearing by 1
      2 years of age. MCP-1-reactive neurons in the dentate nucleus and inferior
      olivary nucleus showed temporal increases similar to that of Purkinje cells. In
      the pons, however, MCP-1 reactivity was low in neurons of the pontine nuclei
      persisting from the fetal to the adult period, and was very low and short in the
      reticular formation and cranial nerve nuclei during the fetal and/or neonatal
      period. MCP-1 Western blotting of the cerebellar cortex confirmed the specificity
      of the immunohistochemistry. Our results suggest that MCP-1 may be related to the
      maturation of Purkinje cells, the dentate nucleus, the inferior olivary nucleus,
      and their network, promoting the growth of dendrites and synapses. Furthermore,
      MCP-1 may also be useful for the study of abnormal neuron development and
      ischemic damage.

PMID- 10082251
TI  - Trial of antiepilepsirine (AES) in children with epilepsy.
AB  - Antieplepsirine (AES) is a new antiepileptic drug (AED) which was originally
      extracted from a Chinese folk remedy, and is now chemically characterized and
      synthesized. Its chemical structure is different from those of other available
      AEDs. Animal experiments involving AES demonstrated significant antiepileptic
      activity. Only a few clinical studies of AES with open trial have been resorted,
      none of which were on children. A 6.5 month, add-on, double-blind, placebo
      controlled, randomized, cross-over study on AES (10 mg/kg per day) was conducted
      on epileptic children (aged 1-14 years) refractory to treatment with standard
      AEDs. The seizure frequency was recorded, and the blood levels of AES and other
      co-medicated AEDs (phenobarbital, phenytoin, carbamazepine and valproate) were
      determined. Although not planned, patients or parents were allowed to refuse to
      cross-over to the alternate therapy. The results were compared to the children
      who crossed-over as well as for the entire group during the first 3 months of
      randomized treatment. A total of 58 children entered, but only 34/58 children
      completed the cross-over study. The 24 children whose parents refused to let them
      be crossed-over continued the original study treatment (AES or placebo) for the
      entire 6 months. There was no statistically significant difference in seizure
      control when the entire group of 58 patients was compared to a parallel study
      group for the first 3 months of therapy (P = 0.178). There was a significant
      difference (P<0.01) in seizure control between AES and placebo treatment for the
      34 patients who completed the entire cross-over study. No significant changes
      were seen in the blood level of other AEDs, and no serious acute side effects
      were observed. The results of the present study indicate the efficacy of AES for
      epileptic children with refractory seizures.

PMID- 10082252
TI  - Synaptophysin immunocytochemistry with thermal intensification: a marker of
      terminal axonal maturation in the human fetal nervous system.
AB  - Synaptophysin is a protein of synaptic vesicles and may be demonstrated in tissue
      sections of human brain and spinal cord by immunocytochemistry using a monoclonal
      antibody. Synaptophysin immunoreactivity was studied in paraffin-embedded
      sections of the central nervous system (CNS) in 14 normal human fetuses and
      neonates ranging in age from 8 to 41 weeks gestation, and in three brains with
      heterotopic neurons or malformations. A progressive expression of synaptophysin
      is seen in axonal terminals within grey matter in various parts of the CNS,
      beginning in the ventral horns of the spinal cord and brainstem tegmentum at 12
      14 weeks. In the cerebellum, the molecular layer shows a band of reactivity from
      18 weeks; by term two parallel bands of synaptophysin are seen in the molecular
      layer and reactivity also is demonstrated in the Purkinje and internal granular
      layers. In the cerebral neocortex, the molecular zone has weak synaptophysin
      reactivity as early as 10 weeks, though reactivity is not detected in the deep
      layers of the cortical plate until 19 weeks and in layers 2-4 until 25 weeks
      gestation. Synaptophysin reactivity is strong at the surface of neurons but not
      detected in their somatic cytoplasm; coarsely beaded reactivity within the
      neuropil probably corresponds to synaptic vesicles in terminal axons. Similar
      granular synaptophysin reactivity is seen around heterotopic neurons in the
      subcortical white matter, in dysgenesis of the cerebellar cortex and in the
      residual anencephalic forebrain. Thermal intensification by heating the
      incubating solution in a microwave oven often enhances immunoreactivity because
      of more complete antigen retrieval and is recommended for tissue stored in
      formalin or in paraffin for long periods. Synaptophysin provides a useful tissue
      marker of synaptogenesis during normal development and in cerebral dysgeneses,
      and may provide useful correlations with functional imaging of the brain in
      living patients. Used in conjunction with other neuronal markers, the expression
      of synaptophysin in terminal axons of distant neurons, in temporal relation to
      the maturation of the neurons they innervate, may provide clues to the
      pathogenesis of epilepsy in early infancy.

PMID- 10082253
TI  - Immunolabelling of spliceosomes in sections and cultured astrocytes of human
      fetal brain tissue.
AB  - In the cell nucleus first large pre-mRNAs are synthesized which contain protein
      coding as well as non-coding sequences. The latter are removed in a process
      called splicing which takes place in nuclear spliceosomes. These spliceosomes
      consist among others of protein factors, such as the splicing factor SC35 being
      abundant in speckled regions of the cell nucleus. This study aims at determining
      immunostaining patterns using anti-SC35 in sections of the human fetal
      prosencephalon and cultured human astrocytes. Within the allocortical entorhinal
      region of the fifth gestational month the number, size and distribution of SC35
      positive speckles varies considerably among the laminae which can, thus, clearly
      be delineated. The immature isocortical plate, however, does not display a
      laminar arrangement at this developmental stage. Differential immunostaining
      patterns can be seen in subcortical areas. Cultured human astrocytes reveal
      numerous speckles occupying a large portion of the nucleoplasm. On account of the
      SC35-immunostaining patterns no distinction of subpopulations of astrocytes is
      possible. The results demonstrate that SC35-immunoreactive speckles show lamina
      and area-specific characteristics of human fetal brain sections. Conspicuous
      differences in number, size and distribution of speckles are visible in different
      cytoarchitectonic structures; thus, architectonic borders stand out clearly in
      SC35-immunopreparations. The occurrence of area-specific immunolabelling of
      nuclear speckle domains reflects neuronal differentiation at the pre
      translational level. It may be assumed that a distinct set of proteins, generated
      by a definite nerve cell type, can be correlated with a distinct morphology of
      spliceosomes. The in vitro finding indicates that anti-SC35 may well be used as a
      tool to study possible alterations of the speckles after, for instance,
      application of growth factors.

PMID- 10082254
TI  - Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in
      Rett syndrome.
AB  - We studied the circadian rhythm of serum melatonin levels in two patients with
      classical Rett syndrome having severe sleep disorders; serum melatonin levels
      were measured before and during melatonin treatment using radioimmunoassay.
      Patient 1 had a free-running rhythm of sleep-wake cycle from 3 years of age. At
      the age of 4 years, the peak time of melatonin was delayed 6 h compared to normal
      control and the peak value was at the lower limit. Patient 2 had a fragmented
      sleep pattern accompanied by night screaming from 1 year and 6 months of age. At
      the age of 10 years, the peak time of melatonin secretion was normal but the peak
      value was at the lower limit. These patients were given 5 mg melatonin orally
      prior to bedtime. Exogenous melatonin dramatically improved the sleep-wake cycle
      in patient 1. In patient 2, exogenous melatonin showed a hypnotic effect but
      early morning awakenings occurred occasionally. When melatonin treatment was
      stopped, the sleep disorders recurred and re-administration of 3 mg melatonin was
      effective in both patients. The effect was maintained over 2 years without any
      adverse effects. These findings suggests that sleep disorders in patients with
      Rett syndrome may relate with an impaired secretion of melatonin.

PMID- 10082255
TI  - Pathological study on sibling autopsy cases of the late infantile form of
      neuronal ceroid lipofuscinosis.
AB  - We report autopsy cases of two brothers with the late infantile form of neuronal
      ceroid lipofuscinosis (LINCL) and examine apoptotic cell death in autopsied
      brains. Both patients showed psychomotor developmental delay, cerebellar ataxia,
      convulsions, visual disturbance and myoclonus, and they became bedridden around
      the age of 6-7 years. Macular changes, mimicking cherry-red spots, were observed
      on funduscopy, but conjunctival biopsy failed to disclose storage materials. In
      these cases, the autopsies demonstrated severe atrophy with neuronal loss and
      gliosis throughout the brain and spinal cord, except the hypothalamic neurons and
      motor neurons in the brain-stem and spinal cord, and autofluorescent lipofuscin
      like materials of two types, fine granular deposits and coarse round bodies, were
      stored in the remaining neurons and glial cells, and in the epithelial cells of
      various visceral organs. Immunostaining for mitochondrial subunit C visualized
      the fine granular deposits but not the coarse round bodies. The nuclei of neurons
      and glia cells were stained by in situ nick end labeling, which was more
      pronounced in the younger case, although the expression of both bcl-2 and bcl-x
      was not significantly altered in these cases. It is suggested that
      immunohistochemistry for subunit C may be useful for diagnosis of NCL, and
      further investigations are necessary to clarify the relationship between LINCL
      and apoptosis, especially in severely affected cases.

PMID- 10082256
TI  - Sturge--Weber syndrome: report of an unusual cutaneous distribution.
AB  - This is an 11 month old girl who has been referred to our institute for a seizure
      disorder. Her physical examination showed angiomas on the left side of her face,
      and more extensive and prominent ones on her palms and soles. Her right face and
      arm were smaller than the left, associated with hypotonia and moderate weakness
      in the right forearm. Computerized tomography of head showed intracranial
      calcification in the left fronto-parietal region, and brain MRI, with gadolinium,
      revealed an extensive leptomeningeal angioma over the entire left hemisphere.
      This case was diagnosed as Sturge-Weber syndrome with unusual cutaneous
      manifestations.

PMID- 10082257
TI  - Increased discriminative stimulus potency of phencyclidine in C57B1/6 mice
      infected with the LP-BM5 retrovirus.
AB  - Drug discrimination procedures in mice are used to study the neuropharmacology of
      a wide variety of drugs. In C57 B1/6 mice, infection with the LP-BM5 murine
      leukemia virus leads to a syndrome (murine acquired immunodeficiency syndrome
      MAIDS) characterized by immunocompromise, neurochemical alterations, and learning
      and memory deficits. Because the neurochemical and behavioral changes suggest
      that altered glutamatergic neurotransmission follows LP-BM5 infection, we studied
      the effects of infection on discriminative stimulus properties of phencyclidine
      (PCP), a Ca2+ channel blocker at NMDA receptors. We also tested D-amphetamine and
      dizocilpine to assess the specificity of the discrimination. As expected,
      dizocilpine produced PCP-like responding. After animals were trained to
      discriminate PCP from saline, they were inoculated with LP-BM5 and the PCP dose
      response functions repeatedly determined. The potency of PCP in this procedure
      was unchanged 3 weeks after infection, but was increased approximately fivefold 6
      and 9 weeks after infection. Amphetamine 9 weeks after inoculation did not
      produce PCP-like responding, showing that the results were not caused by a loss
      of specificity of the discrimination. The time course for changes in PCP potency
      is similar to those of other behavioral and neurochemical changes reported after
      LP-BM5 infection. The results are consistent with an action of LP-BM5 infection
      at glutamatergic synapses.

PMID- 10082258
TI  - Nitric oxide synthase inhibitors do not substitute in rats trained to
      discriminate phencyclidine from saline.
AB  - Release of nitric oxide occurs as a consequence of glutamate stimulation of NMDA
      receptors and is dependent upon calcium-calmodulin activation of the enzyme
      nitric oxide synthase. Since nitric oxide may serve as an intracellular messenger
      for NMDA glutamatergic neurons, it could be hypothesized that blockade of its
      synthesis may produce pharmacological effects similar to those of NMDA receptor
      antagonists. The purpose of the present study was to compare the effects of
      nitric oxide synthase inhibitors to those of the high affinity NMDA open channel
      blocker phencyclidine in drug discrimination, a pharmacologically selective
      procedure in which phencyclidine produces distinctive effects. Rats were trained
      to discriminate 2 mg/kg phencyclidine from saline in a standard two-lever
      discrimination task with food reward. Whereas phencyclidine dose-dependently
      substituted for itself, 7-nitroindazole, L-NAME (N(G)-nitro-L-arginine methyl
      ester), and L-NOARG (N(G)-nitro-L-arginine) failed to substitute for
      phencyclidine when administered intraperitoneally. L-NAME and 7-nitroindazole
      were tested up to doses that disrupted responding, providing evidence that a
      behaviorally-relevant dosage range was evaluated. Although these results conflict
      with those of a previous study which found that nitric oxide synthase inhibitors
      substituted for phencyclidine and produced phencyclidine-like catalepsy in
      pigeons, they are consistent with research showing that these drugs did not
      produce phencyclidine-like pharmacological effects in behavioral procedures in
      rats.

PMID- 10082259
TI  - Influence of antineoplastic drugs on morphine analgesia and on morphine
      tolerance.
AB  - The possible influence of cisplatin, methotrexate, adriamycin and vincristine on
      thermal pain threshold, morphine analgesia and development of morphine tolerance
      was investigated in mice. In the hot-plate test, the nociceptive threshold was
      not affected by acute or repeated administration of any of the antineoplastic
      drugs used. The analgesic activity of morphine was significantly reduced by
      pretreatment with cisplatin, intraperitoneally (i.p.) injected at the dose of 2
      mg/kg. In contrast, methotrexate, subcutaneously (s.c.) injected at the dose of 1
      and 5 mg/kg, adriamycin (1 and 3 mg/kg s.c.), vincristine (0.25 and 0.5 mg/kg
      i.p.) and a lower dose of cisplatin (1 mg/kg i.p.) had no effect. The development
      of tolerance to morphine analgesia was delayed by adriamycin but was not
      influenced by the other antineoplastic drugs used. These data show that, of the
      four antineoplastic agents used in this study, cisplatin may interfere in the
      mechanism of action of morphine, and that adriamycin may delay the development of
      opiate tolerance.

PMID- 10082260
TI  - The atypical antipsychotic sertindole enhances efflux of dopamine and its
      metabolites in the rat cortex and striatum.
AB  - Previous studies have shown that sertindole (1-[2-[4-[5-chloro-1-(4-fluorophenyl)
      1H-indol-3-yl]-1-piperidinyl]ethyl ]-2 imidazolidinone), an atypical
      antipsychotic drug that is a potent 5-HT2A and dopamine D2 receptor antagonist,
      preferentially affects mesocorticolimbic rather than mesostriatal dopamine
      neurons. Using in vivo microdialysis in conscious rats, we investigated the
      effects of sertindole on dopamine release and metabolism in the striatum and the
      medial prefrontal cortex. Systemic administration of sertindole dose dependently
      enhanced dopamine release in the medial prefrontal cortex and the striatum to the
      same extent.

PMID- 10082261
TI  - Facilitation of spontaneous defibrillation by moxonidine during regional
      ischaemia in an isolated working rabbit heart model.
AB  - Moxonidine has been shown to be antiarrhythmic during ischaemia in vivo. This
      study aimed to investigate its electrophysiological effects in isolated working
      rabbit hearts in vitro. Monophasic action potential duration, effective
      refractory period and conduction delay were measured at three ventricular sites.
      The hearts were treated before and during ischaemia and reperfusion with vehicle,
      moxonidine (0.01, 0.1 and 1 microM) or labetalol (1 microM). In all groups,
      ventricular fibrillation was always induced during ischaemia. Only 0.1 microM
      moxonidine decreased the incidence of sustained ventricular fibrillation from 86
      to 17%, although it did not affect any electrophysiological parameters measured.
      Similarly, labetolol, an adrenoceptor blocker, facilitated spontaneous
      defibrillation without any electrophysiological effects. In conclusion,
      moxonidine directly facilitates spontaneous defibrillation of ventricular
      fibrillation during ischaemia. Since the same effect is observed with labetalol,
      it is possible that the defibrillatory action of moxonidine is related to its
      peripheral antiadrenergic activity, although other mechanisms cannot be excluded.

PMID- 10082262
TI  - Reduction of myocardial injury by the EP3 receptor agonist TEI-3356. Role of
      protein kinase C and of K(ATP)-channels.
AB  - The effects of the prostanoid EP3 receptor agonist TEI-3356 on either protein
      kinase C or ATP-sensitive (K(ATP)) K+ channels and on the infarct size caused by
      regional myocardial ischaemia and reperfusion in the rat were investigated. Male
      Wistar rats (n = 72) were subjected to 25 min occlusion of the left anterior
      descending coronary artery followed by 2 h of reperfusion. TEI-3356 (1
      microg/kg/min i.v., n = 6) caused a significant reduction in infarct size from
      60+/-3% (control, n = 8) to 38+/-3% of the area at risk. Pretreatment of rats
      with 5-hydroxydecanoate (5 mg/kg i.v., n = 6), a specific inhibitor of K(ATP)
      channels, attenuated the cardioprotective effects of TEI-3356. The reduction in
      infarct size afforded by TEI-3356 was also abolished by the protein kinase C
      inhibitors staurosporine (1 microg/kg i.v., n = 6) and chelerythrine (0.7 mg/kg
      i.v., n = 5). Thus, TEI-3356 reduces myocardial infarct size in the rat by a
      mechanism(s) which involves the activation of protein kinase C and the opening of
      K(ATP)-channels.

PMID- 10082263
TI  - Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to
      ginsenosides in rat aorta: role of K+ channels.
AB  - The aim of the present study was to characterize the endothelium-dependent
      relaxation elicited by ginsenosides, a mixture of saponin extracted from Panax
      ginseng, in isolated rat aorta. Relaxations elicited by ginsenosides were
      mimicked by ginsenoside Rg1 and ginsenoside Rg1, two major ginsenosides of the
      protopanaxatriol group. Ginsenoside Rg3 was about 100-fold more potent than
      ginsenoside Rg1. The endothelium-dependent relaxation in response to ginsenoside
      Rg3 was associated with the formation of cycle GMP. These effects were abolished
      by N(G)-nitro-L-arginine and methylene blue. Relaxations in response to
      ginsenoside Rg3 were unaffected by atropine, diphenhydramine, [D-Pro2, D
      Trp7,9]substance P, propranolol, nifedipine, verapamil and glibenclamide but were
      markedly reduced by tetraethylammonium. Tetraethylammonium modestly reduced the
      relaxation induced by sodium nitroprusside. These findings indicate that
      ginsenoside Rg3 is a major mediator of the endothelium-dependent nitric oxide
      mediated relaxation in response to ginsenosides in isolated rat aorta, possibly
      via activation of tetraethylammonium-sensitive K+ channels.

PMID- 10082264
TI  - The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic
      rings: role of K+ channels.
AB  - The purpose of the present study was to characterize the mechanism underlying the
      direct relaxing activity of ginsenosides on vascular smooth muscle. The total
      ginsenoside mixture, ginsenosides from either the protopanaxadiol group or the
      protopanaxatriol group, and the ginsenoside Rg3 from the protopanaxatriol group
      caused a concentration-dependent relaxation of rat aortic rings without
      endothelium contracted with 25 x 10(-3) M KCl but affected only minimally those
      contracted with 60 x 10(-3) M KCl. Ginsenoside Rg3 was the most potent relaxing
      agonist. Relaxations elicited by ginsenoside Rg3 were markedly reduced by
      tetraethylammonium, a blocker of non-selective K+ channels, but not by
      glibenclamide, a blocker of ATP-sensitive K+ channels. Ginsenoside Rg3
      significantly inhibited Ca2+-induced concentration-contraction curves and the
      45Ca2+ influx in aortic rings incubated with 25 x 10(-3) M KCl whereas these
      responses were not affected in rings incubated with 60 x 10(-3) M KCl.
      Ginsenoside Rg3 caused a time- and concentration-dependent efflux of 86Rb from
      aortic rings that was inhibited by tetraethylammonium but not by glibenclamide.
      These findings indicate that ginsenoside Rg3 is a potent inhibitor of vascular
      smooth muscle tone and that this effect seems to be due to an inhibition of Ca2+
      influx and stimulation of K+ efflux, possibly via activation of
      tetraethylammonium-sensitive K+ channels.

PMID- 10082265
TI  - Different pathways for Ca2+ mobilization by angiotensin II and carbachol in the
      circular muscle of the guinea-pig ileum.
AB  - Ca2+ pathways activated by angiotensin II and carbachol were evaluated in the
      circular muscle of the guinea-pig ileum by recording mechanical and electrical
      activities. Transient contractions induced by angiotensin II were greatly reduced
      by Ca2+ removal from the medium whereas carbachol-induced responses were not
      significantly altered. Nifedipine had no effect on the responses to both
      agonists. A high concentration of tetrodotoxin (0.1 microM) inhibited angiotensin
      II-induced contractile responses without affecting the depolarization, whereas 1
      mM Ni2+ inhibited the mechanical and electrical effects. Neither tetrodotoxin nor
      Ni2+ affected carbachol-induced effects. These results indicate that angiotensin
      II-induced phasic contractions depend on extracellular Ca2+ but not on voltage
      dependent L-type Ca2+ channels. It is suggested that angiotensin II activates
      Ni2+-sensitive Na+ and non-specific cationic channels, whereas the responses to
      carbachol are dependent on receptor-activated Ca2+ release. Furthermore the
      different response of the longitudinal and circular muscles to the inhibitory
      effects of tetrodotoxin and Ni2+ on the angiotensin II- and carbachol-induced
      contractions indicates that these agonists exert their own myogenic effects on
      each layer and are able to trigger different Ca2+ mobilization pathways.

PMID- 10082266
TI  - Haloperidol-induced changes in glutathione and energy metabolism: effect of
      nicergoline.
AB  - The aim of this study was to evaluate the possible effects of nicergoline, a
      semisynthetic ergot derivative, on the biochemical changes observed during
      chronic treatment with haloperidol in male Sprague-Dawley rats. Chronic treatment
      with haloperidol induced a significant decrease in the cellular glutathione (GSH)
      content in selected areas of the brain (cerebellum, striatum and cortex) and in
      the liver. Prolonged nicergoline administration was able to antagonize the
      haloperidol-induced GSH decrease, maintaining the GSH concentration at levels
      comparable to those observed in the control group. Analysis of the energy charge
      revealed changes similar to those observed for GSH: haloperidol induced a
      significant decrease in ATP and energy charge that was completely reversed by
      repeated nicergoline administration. In conclusion, chronic treatment with the
      classical antipsychotic haloperidol induces profound biochemical changes in the
      brain and in the liver. Nicergoline treatment is able to counteract the
      haloperidol-induced decrease in GSH levels and energy charge, suggesting a
      potential role of the drug in the treatment of neuroleptic-induced side effects.

PMID- 10082267
TI  - Effects of chronic unilateral internal pudendal arterial occlusion on reactivity
      of isolated corpus cavernosum strips from rabbits.
AB  - An animal model was developed to elucidate the effect of chronic obstruction of
      the internal pudendal artery on the responsiveness of the corpus cavernosum. In
      male albino rabbits, the internal pudendal artery was chronically ligated
      unilaterally with a silk tie and the occlusion was maintained for 1 month. The
      control group was sham-operated. The reactivity of corpus cavernosum tissue from
      the ligated animals and the control animals was studied in organ chambers.
      Unilateral chronic ligation of the internal pudendal artery caused an impaired
      contractile response to alpha-adrenoceptor stimulation with decreased Em and pD2
      values and an impaired relaxant response to electrical field stimulation but
      resulted in a marked increase in the endothelium-dependent relaxant response to
      carbachol with an increased pD2 value. However chronic obstruction of the
      pudendal artery had no effect on adenosine-, papaverine- and sodium nitroprusside
      induced relaxant responses, and there was no change in agonist potency. These
      data indicate that altered penile hemodynamics have an effect on the reactivity
      of the corpus cavernosum and may contribute to the etiology of impotence.

PMID- 10082268
TI  - Pertussis toxin increases isoproterenol induced relaxation in field-stimulated
      ileum.
AB  - We investigated the effects of pertussis toxin on contraction in field-stimulated
      guinea pig ileum in the absence and presence of isoproterenol. Field-stimulation
      elicited pertussis toxin-insensitive contractions. Cumulative addition of
      isoproterenol produced a maximal 52% reduction in the contractile response.
      Following pertussis toxin-treatment, the maximal inhibitory effect of
      isoproterenol increased to 83%. Pertussis toxin had no effect on the ability
      isoproterenol to inhibit contractions elicited by histamine agonists. Our results
      suggest that the increased effectiveness of isoproterenol in pertussis toxin
      treated ileum is due to an uncoupling of the muscarinic M2 receptor contractile
      mechanism.

PMID- 10082269
TI  - Presence of constitutive endothelial nitric oxide synthase immunoreactivity in
      urothelial cells of hamster proximal urethra.
AB  - Electrical field stimulation caused frequency-dependent relaxations in
      precontracted strips of hamster proximal urethra, which were attenuated by L-N(G)
      nitroarginine methyl ester (10(-4) M) and completely blocked by tetrodotoxin (10(
      6) M). Strips of hamster urethra devoid of urothelium showed reduced relaxant
      responses to electrical field stimulation which were abolished by L-N(G)
      nitroarginine methyl ester (10(-4) M). Western blot analysis showed the presence
      of a constitutive endothelial nitric oxide synthase in the urothelial layer,
      suggesting that urothelium may release nitric oxide in response to electrical
      field stimulation and that this release is blocked by tetrodotoxin. It is
      suggested that the urothelium may contribute to relaxations of the smooth muscle
      of hamster urethra produced by nerve stimulation.

PMID- 10082270
TI  - JTT-608 controls blood glucose by enhancement of glucose-stimulated insulin
      secretion in normal and diabetes mellitus rats.
AB  - We investigated the pharmacological effects of a new anti-hyperglycemic agent,
      JTT-608 [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid], in normal and
      neonatally streptozotocin-treated rats. In normal rats, JTT-608 improved glucose
      tolerance at 3-30 mg/kg, doses that did not cause a decrease in fasting blood
      glucose levels. In contrast, tolbutamide (10-100 mg/kg) and glibenclamide (1-3
      mg/kg) caused a persistent decrease in fasting blood glucose levels, and
      tolbutamide only improved glucose tolerance at 10-100 mg/kg. Furthermore, JTT-608
      (3-30 mg/kg) enhanced insulin secretion only with glucose stimulation, but
      tolbutamide (10-100 mg/kg) enhanced it both with and without glucose stimulation.
      In neonatally streptozotocin-treated rats, JTT-608 (10-100 mg/kg) improved
      glucose tolerance with enhanced insulin secretion in the oral glucose tolerance
      test and meal tolerance test. Additionally, JTT-608 improved glucose tolerance
      dose dependently, but the effect of tolbutamide reached a plateau. We conclude
      that JTT-608 is an enhancer of glucose-stimulated insulin secretion.

PMID- 10082271
TI  - Loreclezole and La3+ differentiate cerebellar granule cell GABA(A) receptor
      subtypes.
AB  - The effects of loreclezole and La3+ on native cerebellar GABA(A) receptors were
      compared between GABA(A) receptor alpha6 subunit-deficient (alpha6-/-) and
      wildtype mouse lines, produced through homologous recombination, using t
      [35S]butylbicyclophosphorothionate ([35S]TBPS) autoradiography in brain sections.
      In the alpha6 subunit-deficient mice, the GABA receptor antagonistic ability of
      La3+ was abolished in the cerebellar granule cell layer, consistent with its
      opposite actions on alpha6- and of alpha1 subunit-containing receptors. La3+
      significantly potentiated the action of GABA in the molecular layer of the alpha6
      /- mice, but not in that of the wildtype mice. The potentiation of agonistic GABA
      inhibition of [35S]TBPS binding by loreclezole in alpha6-/- granule cells was
      reduced, suggesting an emergence of low-affinity GABA(A) receptors. The present
      results thus identified two ligands that may be useful in studying functional
      roles of cerebellar alpha1 and alpha6 subunit-containing GABA(A) receptor
      subtypes.

PMID- 10082272
TI  - Nerve growth factor, ganglioside and vitamin E reverse glutamate cytotoxicity in
      hippocampal cells.
AB  - The present work showed that glutamate decreased hippocampal cell viability in a
      dose-dependent manner. While no significant effect was observed after cell
      exposure to 0.1 mM glutamate, cell incubation for 0.5 h caused a progressive
      decrease of cell viability, which at 5 mM concentration reached 68% as compared
      to controls. No further effect was observed in the presence of 10 mM glutamate.
      While nerve growth factor (NGF) at the dose of 0.5 ng/ml presented no effect, it
      significantly reduced glutamate cytotoxicity at a higher dose (1 ng/ml)
      increasing the cell viability to 66%. Similarly, cell viabilities in the presence
      of the ganglioside GM, (5 and 10 ng/ml) after glutamate exposure were 19 and 73%,
      respectively. A dose-response relationship was observed after cell incubation
      with vitamin E (0.5 and 1 mM) which resulted in cell viability of the order of 34
      and 70%, respectively. Surprisingly, a potentiation of the effect was observed
      after the association of NGF (0.5 ng/ml) plus ganglioside GM1 (5 ng/ml) or
      vitamin E (0.5 mM) plus ganglioside GM1 (5 ng/ml), after pre-incubation with
      glutamate. In these conditions, significantly higher viabilities were
      demonstrated (66 and 71% for the two associations, respectively) as compared to
      each one of the compounds alone (NGF 0.5 ng/ml--29.5%; ganglioside GM1 5 ng/ml-
      19.4%). However, no potentiation was seen after the association of NGF plus
      vitamin E on glutamate pre-exposed cells. These results showed a cytoprotective
      effect of ganglioside GM1, NGF and vitamin E on the glutamate-induced
      cytotoxicity in rat hippocampal cells.

PMID- 10082273
TI  - Inhibition by fluoxetine of voltage-activated ion channels in rat PC12 cells.
AB  - The effects of fluoxetine (Prozac) on voltage-activated K+, Ca2+ and Na+ channels
      were examined using the whole-cell configuration of the patch clamp technique in
      rat pheochromocytoma (PC12) cells. When applied to the external bath solution,
      fluoxetine (1, 10, 100 microM) decreased the peak amplitude of K+ currents. The
      K+ current inhibition by fluoxetine (10 microM) was voltage-independent and the
      fraction of current inhibition was 39.7-51.3% at all voltages tested (0 to +50
      mV). Neither the activation and inactivation curves nor the reversal potential
      for K+ currents was significantly changed by fluoxetine. The inhibition by
      fluoxetine of K+ currents was use- and concentration-dependent with an IC50 of
      16.0 microM. The inhibition was partially reversible upon washout of fluoxetine.
      The action of fluoxetine was independent of the protein kinases, because the
      protein kinase C or A inhibitors (H-7, staurosporine, Rp-cAMPS) did not prevent
      the inhibition by fluoxetine. Intracellular infusion with GDPbetaS or
      pretreatment with pertussis toxin did not block the inhibitory effects of
      fluoxetine. The inhibitory action of fluoxetine was not specific to K+ currents
      because it also inhibited both Ca2+ (IC50 = 13.4 microM) and Na+ (IC50 = 25.6
      microM) currents in a concentration-dependent manner. Our data indicate that when
      applied to the external side of cells, fluoxetine inhibited voltage-activated K+,
      Ca2+ and Na+ currents in PC12 cells and its action on K+ currents does not appear
      to be mediated through protein kinases or G proteins.

PMID- 10082274
TI  - Selectivity of diadenosine polyphosphates for rat P2X receptor subunits.
AB  - The pharmacological activity of diadenosine polyphosphates was investigated at
      three recombinant P2X receptors (rat P2X1, rat P2X3, rat P2X4) expressed in
      Xenopus oocytes and studied under voltage-clamp conditions. For the rat P2X1
      receptor, only P1,P6-diadenosine hexaphosphate (Ap6A) was a full agonist yet 2-3
      folds less potent than ATP. At rat P2X3, P1,p4-diadenosine tetraphosphate (Ap4A),
      P1,P5-diadenosine pentaphosphate (Ap5A) and Ap6A were full agonists and more
      potent than ATP. Ap4A alone was equipotent with ATP at rat P2X4, but only as a
      partial agonist. Compared to known data for rat P2X2 and human P2X1 receptors,
      our findings contrast with rat P2X2 where only Ap4A is a full agonist although
      four folds less potent than ATP. At rat and human orthologues of P2X1, Ap5A was a
      partial agonist with similar potency. These data provide a useful basis for
      selective agonists of P2X receptor subunits.

PMID- 10082275
TI  - Cocaine decreases the glycine-induced Cl- current of acutely dissociated rat
      hippocampal neurons.
AB  - The effects of cocaine on glycine-induced Cl- current (I(GLY)) of single neurons,
      freshly isolated from the rat hippocampal CA1 area, were studied with
      conventional whole-cell recording under voltage-clamp conditions. Cocaine
      depressed I(GLY) in a concentration-dependent manner, with an IC50 of 0.78 mM.
      Preincubation with 1 mM cocaine alone had no effect on I(GLY), suggesting that
      resting glycine channels are insensitive to cocaine. The depression of I(GLY) by
      cocaine was independent of membrane voltage. Internal cell dialysis with 1 mM
      cocaine failed to modify I(GLY). Because the depression of I(GLY) was
      noncompetitive, cocaine may act on the glycine receptor-chloride ionophore
      complex at a site distinct from that to which glycine binds. The cocaine
      suppression of I(GLY) was unaffected by 1 microM tetrodotoxin and 1 microM
      strychnine. Blockers of protein kinase C (Chelerythrine), kinase A (N-[2-((p
      bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl, (H-89)) and Ca
      calmodulin-dependent kinase (1-[N,O-bis(5-isoquinoline-sulfonyl)-N-methyl-L
      tyrosyl]-4-phenylpiperaz ine (KN-62)) were also ineffective, which suggests that
      these phosphorylating mechanisms do not modulate cocaine-induced suppressant
      action on I(GLY). This extracellular, strychnine-independent depression of I(GLY)
      may contribute to cocaine-induced seizures.

PMID- 10082276
TI  - Nonsteroidal anti-inflammatory drugs may prevent colon cancer through suppression
      of hepatocyte growth factor expression.
AB  - Nonsteroidal anti-inflammatory drugs which inhibit cyclooxygenase have been
      reported to suppress colon carcinogenesis. However the mechanism has not yet been
      elucidated. Growth factors such as hepatocyte growth factor, which are produced
      by fibroblasts, have been shown to be important in carcinogenesis and the
      progression of various human cancers. In the present study, we tested the
      hypothesis that nonsteroidal anti-inflammatory drugs inhibit hepatocyte growth
      factor expression through an endogenous prostaglandin-mediated pathway in
      cultured human colonic fibroblasts. Human colonic fibroblasts were obtained from
      a resected colon and cultured. Hepatocyte growth factor and prostaglandin E2 were
      measured by enzyme-linked immunosorbent assay. Induction of cyclooxygenase-1 and
      cyclooxygenase-2 protein was estimated by immunoblotting. Prostaglandins
      increased hepatocyte growth factor production significantly in a dose- and time
      dependent manner. Cholera toxin and 8-bromo cAMP also stimulated hepatocyte
      growth factor production. Further, prostaglandin E1 significantly increased
      cellular cAMP. The prostaglandin EP2 and EP4 receptors were detected by reverse
      transcription-polymerase chain reaction. Interleukin-1beta dramatically increased
      prostaglandin E2 production and significantly stimulated hepatocyte growth factor
      synthesis. Interleukin-1beta induced cyclooxygenase-2 but not cyclooxygenase-1
      protein. Indomethacin significantly reduced interleukin-1beta-induced
      prostaglandin E2 release and hepatocyte growth factor production. These results
      suggest that prostaglandin is a factor for the production of hepatocyte growth
      factor by human colonic fibroblasts. Nonsteroidal anti-inflammatory drugs may
      suppress colon carcinogenesis, in part, through the suppression of hepatocyte
      growth factor expression by inhibiting endogenous prostaglandin production.

PMID- 10082277
TI  - Neuropharmacological assessment of potential dopamine D4 receptor-selective
      radioligands.
AB  - Radiolabeled dopamine D4 receptor-selective agents ([3H]1-benzyl-4-[ N-(3
      isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [3 H]PNU-101958. and
      [125I]1-[4-iodobenzyl]-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]
      aminopiperidine; [125I]RBI-257) were prepared and characterized. With D4.2- and
      D2L receptor-transfected cell membranes, [3H]PNU-101958 showed high dopamine D4
      receptor affinity and selectivity, and potent inhibition by dopamine D4 receptor
      selective compounds. However, its binding with rat brain homogenates showed
      little regional selectivity, and pharmacology inconsistent with selective
      dopamine D4 receptor labeling. Autoradiography indicated partial displacement of
      [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional
      selectivity, and lack of selective labeling with [125I]RBI-257. The results
      encourage further efforts to develop better dopamine D4 receptor-selective
      radioligands.

PMID- 10082278
TI  - Tympanic membrane displacement patterns in experimental cholesteatoma.
AB  - Tympanic membrane (TM) stiffness changes in the pars tensa in response to
      experimentally induced ear canal cholesteatoma by obstruction of the ear canal
      were studied. To this aim TM displacement versus pressure was measured with a
      high resolution, differential moire interferometer. The measurements were
      performed on fresh, isolated gerbil temporal bones after removal of the
      cholesteatoma bulk. Besides an overall stiffness reduction we found that local
      stiffness variations were present in nine out of 18 studied ears. The stiffness
      changes as a function of time after ear canal obstruction had a pattern similar
      to those previously shown to develop in response to various forms of otitis
      media, showing that the TM stiffness properties decrease in a similar way in
      response to different inflammatory middle ear diseases. The stiffness changes
      correlated with an increased overall TM thickness and increased thickness of the
      lamina propria in particular as measured in histology sections. The stiffness
      changes may play an important role in the pathophysiology of cholesteatoma.

PMID- 10082279
TI  - Determination of hair cell degeneration and hair cell death in neomycin treated
      cultures of the neonatal rat cochlea.
AB  - The spatial-temporal course of hair cell degeneration and hair cell death was
      examined in the mammalian cochlea following aminoglycoside treatment. Organotypic
      cultures were established from postnatal rats (P3) and treated with 1 mM neomycin
      sulfate for 12-48 h and analyzed using a live/dead assay under epifluorescence
      microscopy. Live hair cells were labeled with calcein, a probe whose fluorescence
      and cellular retention depends upon intracellular esterase activity and cell
      membrane integrity, respectively. Hair cell death was determined by ethidium
      homodimer-1, a probe that can enter cells with compromised cell membranes only.
      Inside the cell it binds to DNA. Hair cell morphology was also examined using
      phalloidin labeling, scanning electron microscopy and semi-thin section analysis.
      Results showed that hair cell degeneration and hair cell death occurred in a time
      dependent gradient from base to apex. After 48 h of neomycin treatment, most
      apical hair cells survived while most basal hair cells died. Calcein labeling
      provides a sensitive functional assay for measuring hair cell survival.

PMID- 10082280
TI  - Cisplatin ototoxicity and the possibly protective effect of alpha-melanocyte
      stimulating hormone.
AB  - It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so
      called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our
      group has found that cisplatin-induced ototoxicity can also be reduced or
      prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766
      (Hamers et al., 1994; De Groot et al., 1997). The present study was designed to
      investigate the possibly ameliorating effects of the physiologically more
      relevant naturally occurring neuropeptide alpha-melanocyte stimulating hormone
      (alpha-MSH) upon cisplatin ototoxicity and to compare its protective effects to
      those of ORG 2766. For eight consecutive days guinea pigs were treated with
      cisplatin at a concentration of either 1.5 mg/kg/day or 2 mg/kg/day. Animals were
      co-treated with either alpha-MSH (75 microg/kg/day), ORG 2766 (75 microg/kg/day),
      or a sham injection containing physiological saline. Electrocochleography and
      hair cell counts were performed. Treatment with 1.5 mg/kg/day cisplatin resulted
      in a large variability of the morphological and electrophysiological data, a
      variability that might have masked possible effects of ORG 2766 and alpha-MSH.
      Treatment with 2 mg/kg/day cisplatin caused less variable, severe reductions in
      the compound action potentials and cochlear microphonics combined with basal and
      middle-turn outer hair cell loss in five out of six animals. However, in the
      alpha-MSH co-treated groups, two out of six animals could be classified as
      normal, two animals as moderately affected and two animals as severely affected.
      In the ORG 2766 co-treated group we found three animals that were not affected
      and three animals that were severely affected. We conclude that the protective
      effects of alpha-MSH and ORG 2766 co-treatment are comparable and that alpha-MSH
      might be clinically useful in protecting against cisplatin-induced ototoxicity.

PMID- 10082281
TI  - Attenuation of aminoglycoside-induced cochlear damage with the metabolic
      antioxidant alpha-lipoic acid.
AB  - Free radical generation is increasingly implicated in a variety of pathological
      processes, including drug toxicity. Recently, a number of studies have
      demonstrated the ability of gentamicin to facilitate the generation of radical
      species both in vivo and in vitro, which suggests that this process plays an
      important role in aminoglycoside-induced ototoxicity. Free radical scavengers are
      compounds capable of inactivating free radicals, thereby attenuating their tissue
      damaging capacity. In this study we have determined the ability of the powerful
      free radical scavenger alpha-lipoic acid (100 mg/kg/day) to attenuate the
      cochlear damage induced by a highly ototoxic regimen of the aminoglycoside
      amikacin (450 mg/kg/day, i.m.). Experiments were carried out on pigmented guinea
      pigs initially weighing 200-250 g. Changes in cochlear function were
      characterized as shifts in compound action potential (CAP) thresholds, estimated
      every 5 days, by use of chronic indwelling electrodes implanted at the round
      window, vertex, and contralateral mastoid. Results showed that animals receiving
      alpha-lipoic acid in combination with amikacin demonstrated a significantly less
      severe elevation in CAP thresholds compared with animals receiving amikacin alone
      (P < 0.001; t-test). These results provide further evidence of the recently
      reported intrinsic role of free radical generation in aminoglycoside ototoxicity,
      and highlight a potential clinical therapeutic use of alpha-lipoic acid in the
      management of patients undergoing aminoglycoside treatment.

PMID- 10082282
TI  - Evidence for apical K conductance and Na-K-2Cl cotransport in the endolymphatic
      sac of guinea pig.
AB  - The transepithelial potential in the endolymphatic sac (ESP) was recorded up to
      60 min after apical injection of ouabain, bumetanide, quinine, barium,
      tetraethylammonium, and 4-aminopyridine. After control injection, ESP decreased
      by 74% and completely recovered at 30 min. After ouabain, barium, or quinine
      injection, the ESP time course was similar to that in the control group. After
      bumetanide, tetraethylammonium, or 4-aminopyridine injection, complete recovery
      was only observed at 60 min. These results suggest that apical K+ conductance and
      Na-K-2Cl cotransporter could be involved in the genesis of ESP.

PMID- 10082283
TI  - Inferior colliculus stimulation and changes in 2f1-f2 distortion product
      otoacoustic emissions in the rat.
AB  - The external, central and dorsal subnuclei of the inferior colliculus (ICX, ICC,
      ICD respectively) have different patterns of descending projections to the
      periolivary region. We found that electrical stimulation of these subnuclei in
      anesthetized rats causes suppression of 2f1-f2 distortion product otoacoustic
      emissions (DPOAE). The responses in DPOAEs to stimulation of ICX and ICC are
      characterized by a large (7-25 dB), initial suppression which lasted 25-30 s
      (early phase) followed by a sustained smaller (3-15 dB) suppression (late phase).
      ICX stimulation produces the largest suppressions of DPOAEs in both contralateral
      and ipsilateral ears equally. Stimulation of the ICC causes large suppressions in
      the contralateral ear DPOAEs but much smaller than the suppressions of DPOAEs
      caused by ICX stimulation. Stimulation of the ICC causes a much smaller
      suppression in the ipsilateral ear DPOAEs than in the contralateral ear DPOAEs.
      ICD stimulation, however, produces little or no suppression of DPOAEs in either
      ear when compared to other subnuclei. No frequency-specific changes in DPOAEs
      were seen with stimulation of any of the subnuclei of the inferior colliculus
      (IC). Sectioning of middle ear muscles did not negate the suppressive effects of
      IC stimulation on DPOAEs. These findings verify that the IC has a subnucleus
      specific influence over cochlear micromechanics.

PMID- 10082284
TI  - Cationic liposome mediated transgene expression in the guinea pig cochlea.
AB  - Sensorineural hearing loss affects nearly 10% of the American population that is
      refractory to conventional therapy. Gene therapy represents an intervention with
      potential therapeutic efficacy. We studied the feasibility of cationic liposome
      mediated gene transfer within the guinea pig cochlea in vivo following direct
      microinjection into the cochlea. Transgene expression was persistent up to 14
      days in the neurosensory epithelia and surrounding tissue without toxicity and
      inflammation in the target organ. This study represents the first successful use
      of cationic liposomes for cochlear gene transfer thus providing a safe and rapid
      alternative to the use of recombinant viral vectors in gene therapy for inner ear
      disorders.

PMID- 10082285
TI  - Spatial representation of frequency in the rat dorsal nucleus of the lateral
      lemniscus as revealed by acoustically induced c-fos mRNA expression.
AB  - The conventional view, based largely on studies in cats, holds that the dorsal
      nucleus of the lateral lemniscus (DNLL) is tonotopically organized with a dorsal
      (low-frequency) to ventral (high-frequency) representation. Based on the
      topography of projections between the DNLL and inferior colliculus, it has been
      proposed that the rat DNLL has a concentric, inside-to-outside, tonotopic
      organization with high frequencies represented along the rind and low frequencies
      represented in the core. We used acoustic stimulation and c-fos mRNA expression
      to examine this issue. Results suggest that the rat DNLL does have a crude
      tonotopic organization and that this tonotopy has a concentric component.
      Following high-frequency stimulation, labeled neurons were found most frequently
      along the margins of DNLL, although they also tended to be more concentrated
      ventrally. Many fewer neurons labeled following middle-frequency stimulation, and
      these tended to be more uniformly distributed throughout the nucleus. Still fewer
      neurons labeled after low-frequency stimulation and these tended to be scattered
      mostly in the dorsal half of the nucleus. We conclude that: (i) many more neurons
      in the rat DNLL are responsive to high-frequency than to low-frequency acoustic
      stimulation; and (ii) that the frequency representation of the rat DNLL has both
      concentric and dorsal-to-ventral components.

PMID- 10082286
TI  - Increased susceptibility of male rats to kanamycin-induced cochleotoxicity.
AB  - Although clinical observations suggest that males are more susceptible than
      females to ototoxic drugs, controlled experimental studies investigating gender
      susceptibility have not been performed. Aminoglycosides initially attack the
      cochlea's outer hair cells (OHCs). We investigated the effects of the
      aminoglycoside, kanamycin, on electrophysiological function of OHCs in male and
      female rats. Animals were grouped by gender and treated with kanamycin (400
      mg/kg/day kanamycin base, intramuscular injection) or equivolume normal saline.
      Administration was continued until distortion product otoacoustic emissions
      (DPOAEs) suggested a loss in OHC function in kanamycin-treated rats. Males
      treated with kanamycin showed changes in DPOAE thresholds and amplitudes as early
      as treatment day 10 which spread to all test frequencies by treatment day 13. In
      contrast, females treated with kanamycin did not show significant changes in
      thresholds or amplitudes until treatment day 22. The mechanism of increased male
      susceptibility to kanamycin cochleotoxicity has not been determined.

PMID- 10082287
TI  - Nature of the tympanic membrane insertion into the tympanic bone of the rat.
AB  - The nature of the insertion of the tympanic membrane into the tympanic bone was
      studied in the rat during the developmental period ranging from 18 days post
      conception (dpc) to 40 days after birth (dab). Techniques applied were light
      microscopy, electron microscopy and immunohistochemistry with antibodies to
      cytoskeletal proteins: vimentin, desmin and alpha-smooth muscle actin (sma) as
      fibroblast differentiation markers. It was established that the cartilaginous
      annulus of the pars tensa was connected to the tympanic bone by an interface of
      specialised connective tissue. Both the fibrocartilage and the interface were
      derived from the embryonal mesenchyme between the tympanic ring and meatal plate.
      Electron microscopy showed that the interface was composed of two types of
      fibroblast. The majority of these cells were myofibroblasts, which were
      interconnected by junctions and had intimate contact with the collagenous fibres.
      A small number were identified as genuine fibroblasts. Cytoskeletal
      characterisation revealed the presence of three types of cell: V cells which
      expressed vimentin, VA cells which expressed vimentin and alpha-sma and VAD cells
      which expressed vimentin, alpha-sma and desmin. The myofibroblasts expressed
      antigens of both smooth muscle cells (alpha-sma, desmin) and connective tissue
      cells (vimentin). It is suggested that the pars tensa is connected to the
      tympanic bone by a network of contractile cells and fibres. Contraction will move
      the membrane in an outward direction and antagonise the inward retraction by the
      tensor tympani.

PMID- 10082288
TI  - Expression and localization of the Na+-H+ exchanger in the guinea pig cochlea.
AB  - Physiological studies have shown that the Na+-H+ exchanger (NHE) is a major
      carrier protein regulating the intracellular pH in the cells of the cochlea. The
      presence of multiple forms of the exchanger has been demonstrated by the recent
      cloning of four mammalian NHEs, NHE-1 to NHE-4. Despite the structural
      similarity, these NHE isoforms differ in their tissue distribution, kinetic
      characteristics, and responses to external stimuli. The present study was
      undertaken to examine the expression and distribution of four NHE isoforms in the
      guinea pig cochlea. We used reverse transcription-polymerase chain reaction to
      assess the expression of NHE-1-4 isoforms and non-radioactive in situ
      hybridization to examine their localization. Although NHE-2, -3 and -4 isoform
      mRNAs could be detected in the cochlear tissue, the NHE-1 message was
      predominant. Cloned guinea pig NHE-1-4 partial cDNA fragments were highly
      homologous to the corresponding rat NHE isoforms. NHE-1 isoform mRNA was
      distributed in the hair cells, marginal cells, spiral ligament fibrocytes, spiral
      prominence cells and spiral ganglion cells. NHE- localized in a variety of
      cochlear cells would contribute to their differential function.

PMID- 10082289
TI  - Immunolocalization of alpha4 and alpha7 subunits of nicotinic receptor in rat
      cochlear nucleus.
AB  - The rat cochlear nucleus (CN) is known to receive cholinergic input. To
      investigate the prevalence of nicotinic acetylcholine receptor (nAChR),
      immunohistochemistry for alpha4 and alpha7 subunits, which represent nAChRs with
      high binding affinities for nicotine and alpha-bungarotoxin, respectively, was
      performed on perfusion-fixed rat brain sections. Microscopic observations and
      densitometric measurements show dense labeling for alpha7 but not alpha4. Within
      the CN, alpha7 receptors are found in all subregions, with relatively high
      densities in granular regions. The distribution of alpha7 within the CN appears
      to correlate more closely with that of acetylcholinesterase than with mAChR or
      choline acetyltransferase. Our results suggest a role of nicotinic cholinergic
      transmission in the rat CN associated with high affinity for alpha-bungarotoxin.

PMID- 10082290
TI  - Endocochlear potential in focal lesions of the guinea pig cochlea.
AB  - To estimate the correlation between the cochlear lateral wall and endocochlear
      potential (EP), the EP was measured at different time intervals up to 3 weeks at
      cochlear focal lesions made in the guinea pig. Lesions were produced by a
      photochemical reaction between systemically administered Rose Bengal and green
      light illumination in the second cochlear turn. Focal strial lesions (mean
      diameter 975 microm) became apparent under a scanning electron microscope 60 min
      after illumination, and degeneration of the organ of Corti was recognized at 3
      days. The EP was measured continuously for 1 h following onset of the reaction in
      eight ears. In the other ears, EP measurements were done after various intervals
      of time up to 3 weeks. The EP showed two declines from pre-illumination level.
      The first started soon after illumination, reached a minimum value at 25 min, and
      then slightly recovered by 1 h. The second decline appeared at 3 days after
      illumination. In contrast to evident focal morphological degeneration 2 weeks
      post illumination, the EP values had recovered to almost normal. We suggest that
      the sequential changes in the EP were produced depending on the degeneration and
      then repairing processes of the endolymphatic boundary tissues.

PMID- 10082291
TI  - Stimulation of free radical formation by aminoglycoside antibiotics.
AB  - We have previously shown gentamicin to form a redox-active iron chelate. This
      study investigates whether other aminoglycosides can likewise stimulate the
      generation of reactive oxygen species (free radicals). Kanamycin, neomycin and
      streptomycin were compared to gentamicin in intact cells and in cell-free in
      vitro assays using luminescence detection with lucigenin or luminol. Neutrophils
      and Epstein-Barr virus-transformed lymphoblastoid cells served as cell models in
      which a respiratory burst of superoxide was induced by phorbol ester. The
      addition of millimolar amounts of any of the aminoglycosides increased the
      luminescence significantly. The drugs also increased the formation of free
      radicals in an enzymatic (hypoxanthine-xanthine oxidase) and a non-enzymatic
      (phenazine methosulfate-NADH) superoxide-generating system. Half-maximal
      stimulation was reached with (0.4 mM gentamicin, and there was an absolute
      requirement for an electron donor, arachidonic acid. In both intact cells and
      cell-free systems, gentamicin-enhanced luminosity was suppressed by iron
      chelators. These results demonstrate that different aminoglycoside antibiotics
      can stimulate the formation of free radicals in biological and in cell-free
      systems. Luminescence detection is a convenient assay method to investigate the
      redox properties of these drugs.

PMID- 10082292
TI  - Age-related changes in the brainstem auditory evoked potentials of the marmoset.
AB  - Changes in brain-stem auditory evoked potentials (BAEPs) with age were recorded
      in common marmosets (Callithrix jacchus) at the age of 1-2, 6-8 and 10-12 years.
      The auditory function was assessed by thresholds, latencies and amplitudes of
      BAEPs evoked by use of tone burst stimulations with audible frequencies ranging
      from 1 to 99 kHz. Prolongation of the latencies of later waves was observed in
      the animals at the age of 6-8 and 10-12 years at high frequencies, suggesting
      that aging in marmosets, as reported previously in humans and other animals, may
      cause earlier hearing loss at high frequency than at low frequency within the
      hearing range. At 10-12 years of age, the elevations of BAEP thresholds and the
      declines of BAEP amplitudes in older animals were also observed. As the
      differences in the parameters are small, it was suggested that only a moderate
      hearing loss occurred with onset late in life in common marmoset similar to that
      in CBA/Ca mice. Based on the results obtained in this study, BAEP latencies
      appear to be more sensitive indicators than BAEP thresholds and amplitudes for
      the early detection of hearing impairment.

PMID- 10082293
TI  - Intracochlear infusion of buthionine sulfoximine potentiates carboplatin
      ototoxicity in the chinchilla.
AB  - The aim of this experiment was to determine if buthionine sulfoximine (BSO), an
      inhibitor of glutathione (GSH) synthesis, enhances the ototoxicity of
      carboplatin. Osmotic pumps were used to infuse BSO into the right cochleas of 12
      adult chinchillas for 14 days. The left cochleas served as controls. Animals were
      assigned to three groups: a drug control group that did not receive carboplatin,
      a group that received a single dose of carboplatin (25 mg/kg i.p.), and a group
      that received a double dose of carboplatin (25 mg/kg i.p. x 2), with 4 days
      between injections. Carboplatin was administered after three days of BSO pre
      treatment. Ototoxicity was assessed with evoked potentials recorded from
      electrodes implanted in the inferior colliculi (ICPs), distortion product
      otoacoustic emissions (DPOAEs), and cochleograms. BSO infusion itself caused no
      long-term functional or morphological changes. One of four animals treated with
      it single dose of carboplatin showed a significant loss of inner hair cells
      (IHCs), with greater loss in the BSO-treated ear. All animals in the double-dose
      carboplatin group showed marked differences between BSO-treated and control ears.
      Average IHC losses were 59% in BSO-treated ears vs. 18% in control ears.
      Moreover, BSO-treated ears sustained significantly greater outer hair cell (OHC)
      losses than control ears (37% vs. 2%, respectively). ICP and DPOAE response
      amplitudes were reduced slightly in BSO-treated ears relative to control ears,
      consistent with their greater hair cell loss. The results clearly show that BSO
      can enhance carboplatin ototoxicity in the chinchilla, supporting a role of GSH
      and reactive oxygen species in platinum ototoxicity.

PMID- 10082294
TI  - Immunoreactivity of endothelins and endothelin receptor in the stria vascularis
      of the mouse cochlea.
AB  - Immunoreactivities of endothelin-1, endothelin-3, endothelin receptor type A, and
      Na,K-ATPase were investigated in the stria vascularis of adult male WBB6F1 +/+
      mice and in that of W/Wv mutants lacking strial intermediate cells. In the +/+
      mice, electron microscopic immunoreactivity for the endothelins was seen on the
      rough endoplasmic reticulum, Golgi apparatus, cytoplasmic vesicles and lysosomes
      exclusively in the strial intermediate cells by the postembedment method.
      Immunoreactive endothelin receptor A was localized along the plasma membrane of
      strial marginal cells of both wild and mutant types although the immunoreactivity
      of the latter was much less than that of the former by the preembedment method.
      These findings suggest that the endothelins, which are produced in the strial
      intermediate cells, may play a role in the maintenance of the stria vascularis
      function in the +/+ mice. Since the plasma membrane of the marginal cells of the
      W/Wv mice, which do not generate a high positive endocochlear potential, also
      showed immunoreactivity for Na,K-ATPase, it seems likely that the endothelins are
      involved in the activation of sodium pump of the strial marginal cells by
      mediation of endothelin receptor A. In addition, the role of lysosomes in the
      crinophagy of the endothelins in the strial intermediate cells is proposed in the
      +/+ mice.

PMID- 10082295
TI  - Sensorineural hearing loss during development: morphological and physiological
      response of the cochlea and auditory brainstem.
AB  - We have investigated the effects of sensorineural hearing loss on the cochlea and
      central auditory system of profoundly deafened cats. Seventeen adult cats were
      used: four had normal hearing; 12 were deafened neonatally for periods of < 2.5
      years (five bilaterally, seven unilaterally); and one animal had a long-term
      (approximately 8 years) profound bilateral hearing loss. Bipolar scala tympani
      stimulating electrodes were bilaterally implanted in each animal, and
      electrically evoked auditory brainstem responses (EABRs) were recorded in an
      acute study to evaluate the basic physiologic response properties of the deafened
      auditory pathway. The cochleae and cochlear nuclei (CN) of each animal were
      examined with light microscopy. Spiral ganglion cell density in neonatally
      deafened cochleae was 17% of normal, and only 1.5% of normal in the long-term
      deaf animal. There was a 46% reduction in total CN volume in neonatally deafened
      animals compared to normal, and a 60% reduction in the long-term deaf animal.
      Neural density in the anteroventral CN of bilaterally deafened animals was 37%
      higher than normal; 44% higher in the long-term deaf animal. Significantly,
      however, we saw no evidence of a loss of neurones within the anteroventral CN in
      any deafened animal. There was a significant increase in EABR threshold and wave
      IV latency in the deafened animals, and a significant decrease in response
      amplitude and input/output function gradient. Again, these changes were more
      extensive in the long-term deaf animal. These data show that a sensorineural
      hearing loss can evoke significant morphological and physiological changes within
      the cochlea and auditory brainstem, and these changes become greater with
      duration of deafness. It remains to be seen whether these changes can be reversed
      following the introduction of afferent activity via chronic electrical
      stimulation of the auditory nerve.

PMID- 10082296
TI  - Mechanically evoked shortening of outer hair cells isolated from the guinea pig
      organ of Corti.
AB  - Outer hair cells isolated from the mammalian hearing organ have been shown to
      respond to mechanical stimuli at acoustic frequencies by expressing a change in
      cell length (e.g. Canlon et al., 1988). The acoustically evoked response is
      characterised by both a tonic length change following the envelope of the
      stimulus, and a frequency-dependent phasic component. We show here that
      mechanical stimulation at much lower frequencies directed at the cell body also
      elicits length changes of the outer hair cells. When the apical pole of isolated
      outer hair cells was compressed with a quartz fibre, a shortening or contraction
      at the basal pole was observed. Transverse indentation at the lateral membrane
      elicited shortenings at both ends of the cells. The sensitivity to the mechanical
      manipulation was changed by an altered tonicity of the external solution, or
      exposure to salicylate. As the response occurs at very low stimulus frequencies,
      it may account for the mechanism by which the hearing organ responds to the low
      frequency modulation component in complex signals like speech.

PMID- 10082297
TI  - The localisation of spectrally restricted sounds by human listeners.
AB  - The two principal binaural cues to sound location are interaural time differences
      (ITDs), which are thought to be dominant at low frequencies, and interaural level
      differences (ILDs), which are thought to dominate at mid to high frequencies. The
      outer ear also filters the sound in a location dependent manner and provides
      spectral cues to location. In these experiments we have examined the relative
      contribution of these cues to the auditory localisation performance by humans.
      Six subjects localised sounds by pointing their face toward the perceived
      location of stimuli presented in complete darkness in an anechoic chamber.
      Control stimuli were spectrally flat (400 Hz to 16 kHz), while the relative
      contribution of location cues in the low frequency channels was determined using
      noise high passed at 2 kHz and in the high frequency channels using stimuli low
      passed at 2 kHz. The removal of frequencies below 2 kHz had little effect on
      either the pattern of systematic errors or the distribution of localisation
      estimates with the exception of an increase in the size of the standard
      deviations associated with a few rear locations. This suggests considerable
      redundancy in the auditory localisation information contained within a broadband
      sound. In contrast, restricting the target spectrum to frequencies below 2 kHz
      resulted in a large increase in the cone-of-confusion errors as well as a subject
      dependent biasing of the front-to-back or back-to-front confusions. These biases
      and the reduction in localisation accuracy for high pass stimuli at some
      posterior locations are consistent with a contribution of spectral information at
      low frequencies.

PMID- 10082298
TI  - P2X receptor immunoreactivity in the rat cochlea, vestibular ganglion and
      cochlear nucleus.
AB  - P2X receptors have been reported to be involved in neurotransmission in both
      central and peripheral nerves. In the present study, polyclonal antibodies
      against P2X1, P2X2, P2X3, P2X4, P2X5, and P2X6 were used to study the
      distribution of P2X receptors in rat cochlea and vestibulocochlear nerve
      pathways. It was found that in the vestibular ganglion all six types of
      antibodies stained the neurons to different intensities. The strongest signal was
      obtained with the P2X2 antibodies, followed by P2X3 antibodies. The other four
      antibodies produced weak signals, of approximately the same intensity. In the
      spiral ganglion, the six types of antibodies also stained almost all neurons.
      However, the rank order of intensity was different from that in the vestibular
      ganglion: the strongest signal was still obtained with P2X2 antibodies, followed
      by P2X4, P2X1, and P2X3 antibodies. The immunolabelling was much weaker with
      P2X5, and P2X6 antibodies compared with the other four types of antibodies. In
      the cochlea, besides the spiral ganglion neurons, other tissues such as stria
      vascularis, the organ of Corti and the tectorial membrane were labelled
      intensively with P2X2 antibodies only. High density P2X2 immunoreactivity was
      also observed in the vestibulocochlear nerve fibres. In the cochlear nucleus,
      neurons and nerve fibres were stained with the P2X2 antibodies, as were the
      neurons in the trapezoid body. These results suggested that P2 receptors,
      especially the P2X2 receptors, may play important roles in the signal
      transduction involved in the perception of sound and balance.

PMID- 10082299
TI  - Analysis of apoptosis by laser scanning cytometry.
AB  - Flow cytometry techniques that are widely used in studies of cell death, and
      particularly in the identification of apoptotic cells, generally rely on the
      measurement of a single characteristic biochemical or molecular attribute. These
      methods fail to recognize cell death lacking that attribute, as in some examples
      of atypical apoptosis. Since apoptosis was originally defined by morphologic
      criteria, we suggest that for any new cell system the cytometry-defined apoptosis
      be confirmed by morphologic examination. This quality assurance measure is now
      provided by laser scanning cytometry (LSC). LSC measurements of cell fluorescence
      are precise and highly sensitive, comparable to flow cytometry (FCM), and can be
      carried out on cells on slides, permitting cell by cell correlation of
      fluorescence cytometry with visual microscopic morphology. In this report we
      describe adaptations of various flow cytometry techniques for detection of
      apoptosis by laser scanning cytometry. We also describe features unique to LSC
      that are useful in recognizing apoptosis. Hyperchromicity of DNA, reflecting
      chromatin condensation, is evidenced by high maximal pixel values for
      fluorescence of the DNA-bound fluorochrome. Mitochondrial probes that have been
      adapted to LSC to measure the drop in mitochondrial transmembrane potential that
      occurs early in apoptosis include rhodamine 123, 3,3'-dihexiloxadicarbocyanine
      [DiOC6(3)], and the aggregate dye 5,5',6,6'tetrachloro-1,1',3,3'
      tetraethylbenzimidazolcarbocyanine iodide (JC-1). The changes in plasma membrane
      phospholipids and transport function, also early in apoptosis, are probed by a
      combination of the fluoresceinated annexin V and DNA fluorochromes such as
      propidium or 7-aminoactinomycin D. We also review methods of detection of
      apoptosis based on analysis of DNA fragmentation and their application to
      clinical oncology. Visual examination of the presumed apoptotic cells detected by
      cytometry makes it possible to discriminate those that are genuine from
      monocytes/macrophages that have ingested nuclear fragments via apoptotic bodies.
      Applications of flow cytometry and laser scanning cytometry in analysis of cell
      death are discussed and their respective advantages and disadvantages compared.

PMID- 10082300
TI  - Development and validation of a computerized cytomorphometric method to assess
      the maturation of vaginal epithelial cells.
AB  - BACKGROUND: After menopause, declining levels of estrogens may cause vaginal
      discomfort, or so-called "vaginal atrophy." Evaluation of therapies for vaginal
      atrophy may be performed using the so-called "maturation index." The maturation
      index is expressed as the percentage of (para)-basal, intermediate, and
      superficial epithelial cells in a vaginal smear. Manual assessment of the
      maturation index is subject to inter- and intraobserver variations. In this
      study, assessment of the maturation of cells in vaginal smears using automated
      image analysis was investigated. MATERIALS AND METHODS: Automated assessment,
      using a commercially available image analysis system, was performed on
      hematoxylin-eosin-stained cytospin specimens. A training set was constructed by
      an experienced cytotechnologist, based upon visual classification of stored grey
      value images. From this, two discriminant functions (DFs) were calculated capable
      of classifying cells in one of the three types. These cell classifiers were
      capable of classifying 97% of the cells correctly. Data from automated assessment
      were compared with those of classical manual counting. Specimens of 13 mature and
      6 atrophic vaginal specimens were assessed in duplicate, both manually and by
      image analysis, using the DFs. RESULTS: No significant interobserver effect was
      found for image analysis, whereas a significant effect was found for manual
      counting. Both methods were able to distinguish between matured and atrophic
      specimens. CONCLUSIONS: It was concluded that for assessment of vaginal
      maturation, the use of automated image analysis systems is recommended. Besides
      increased reproducibility, image analysis systems yield additional data
      describing the size and shape of the cytoplasm and nucleus of cells, which might
      increase discriminating power.

PMID- 10082301
TI  - Quantitative analysis of cytokeratin network topology in the MCF7 cell line.
AB  - BACKGROUND: In the MCF7 human breast cancer cell line, several patterns of
      cytokeratin networks are observed, depending on the intracellular localization.
      Our hypothesis is that architectural variations of cytokeratin networks depend on
      local tensions or forces appearing spontaneously in the cytoplasm. The aim of
      this work was to discriminate between the different patterns and to quantitate
      these variations. MATERIALS AND METHODS: Image analysis procedures were developed
      to extract cytokeratin filament networks visualized by immunofluorescence and
      confocal microscopy. Two methods were used to segment sets of curvilinear
      objects. The first, the "mesh-approach," based on classical methods of
      mathematical morphology, takes into account global network topology. The second,
      the "filament-approach" (novel), is meant to account for individual element
      morphology. These methods and their combination allow the computation of several
      features at two levels of geometry: global (network topology) and local (filament
      morphology). RESULTS: Variations in cytokeratin networks are characterized by
      their connectivity, density, mesh structure, and filament shape. The connectivity
      and the density of a network describe its location in a local "stress-force" zone
      or in a "relaxed" zone. The mesh structure characterizes the intracellular
      localization of the network. Moreover, the filament shape reflects the
      intracellular localization and the occurrence of a "stress-force" zone.
      CONCLUSIONS: These features permitted the quantitation of differences within the
      network patterns and within the specific filament shapes according to the
      intracellular localization. Further experiments on cells submitted to external
      forces will test the hypothesis that the architectural variations of intermediate
      filaments reflect intracytoplasmic tensions.

PMID- 10082302
TI  - Signal to noise analysis of multiple color fluorescence imaging microscopy.
AB  - BACKGROUND: Various approaches that were recently developed demonstrate the
      ability to simultaneously detect all human (or other species) chromosomes by
      using combinatorial labeling and fluorescence in situ hybridization (FISH). With
      the growing interest in this field, it is important to develop tools for
      optimizing and estimating the accuracy of different experimental methods.
      METHODS: We have analyzed the principles of multiple color fluorescence imaging
      microscopy. First, formalism based on the physical principles of fluorescence
      microscopy and noise analysis is introduced. Next, a signal to noise (S/N)
      analysis is performed and summarized in a simple accuracy criterion. The analysis
      assumes shot noise to be the dominant source of noise. RESULTS: The accuracy
      criterion was used to calculate the S/N of multicolor FISH (M-FISH), spectral
      karyotyping, ratio imaging, and a method based on using a set of broad band
      filters. Spectral karyotyping is tested on various types of samples and shows
      accurate classifications. We have also tested classification accuracy as a
      function of total measurement time. CONCLUSIONS: The accuracy criterion that we
      have developed can be used for optimizing and analyzing different multiple color
      fluorescence microscopy methods. The assumption that shot noise is dominant in
      these measurements is supported by our measurements.

PMID- 10082303
TI  - Quantitative method to determine mRNA levels by reverse transcriptase-polymerase
      chain reaction from leukocyte subsets purified by fluorescence-activated cell
      sorting: application to peripheral cannabinoid receptors.
AB  - BACKGROUND: While cytometry is widely used in the detection of cell proteins, its
      application to quantitative evaluation remains problematic when target proteins
      or receptors are weakly expressed in cells. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) is a technique whose sensitivity and specificity make it
      appropriate for analyzing nucleic acids and thus genes expressed in cells.
      Combining these two techniques, we developed a method to quantify the transcript
      expression of the peripheral cannabinoid receptor (CB2-r) in peripheral blood
      lymphocyte subpopulations and in tonsillar B-cell subpopulations. METHODS: This
      strategy first involves quantitative RT-PCR performed kinetically, followed by
      enzyme detection of PCR products using an oligonucleotide probe sandwich
      hybridization assay onto microplates. RESULTS: B cells exhibit CB2-receptor mRNA
      levels 10 times higher than those of other lymphocyte subsets. Using this
      technique, we observed a modulation of CB2-r mRNA level following tonsillar B
      cell differentiation. Lastly, this new technology was validated by comparing the
      mRNA levels of CB2-r with the expression of CB2-r proteins assayed by flow
      cytometry, using specific CB2-r antibody labelling. CONCLUSIONS: This method
      allows precise measurement of the mRNA of CB2-r performed on cell numbers as low
      as 10(5) after sorting. Its performance, high accuracy, reproducibility, and
      reliability make it a valuable tool for assaying proteins weakly expressed in
      cells.

PMID- 10082304
TI  - Fluorescence monitoring of antibiotic-induced bacterial damage using flow
      cytometry.
AB  - BACKGROUND: Conventional techniques used to assess bactericidal activities of
      antibodies are time-consuming; flow cytometry has been used as a rapid
      alternative. In this study, the membrane potential-sensitive fluorescent probes
      bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)) and Sytox Green,
      the redox dye cyano-2,3-ditolyl tetrazolium chloride (CTC), and the Baclite
      viability test kit were used to assess the effects of ceftazidime, ampicillin,
      and vancomycin on clinical isolates of Pseudomonas aeruginosa, Escherichia coli,
      and Staphylococcus aureus, respectively. METHODS: Bacterial cultures were grown
      to early exponential phase, at which point the antibiotics were added at their
      breakpoint values, and incubation was allowed to continue. At timed intervals,
      samples were stained and flow cytometric analysis was performed on a Skatron
      Argus 100 arc-lamp based dual-parameter flow cytometer. RESULTS: All the dyes
      successfully identified antibiotic-induced damage in the three strains, although
      different fluorescence responses between the dyes were observed. DiBAC4(3) and
      Sytox Green overestimated numbers of nonviable bacteria relative to loss of
      viability as judged by plate counts. CTC, a measure of respiratory activity,
      revealed antibiotic-induced population heterogeneity illus trated by the
      development of several subpopulations. The "live" component of the viability kit
      identified two populations corresponding to viable and nonviable organisms,
      whereas the "dead" component only revealed single populations, the fluorescence
      intensity of which increased with antibiotic exposure. CONCLUSIONS: Flow
      cytometry provides a rapid and sensitive technique for the evaluation of the
      antibacterial activities of antibiotics. The use of a range of fluorophores
      specific for different cellular characteristics may be beneficial, bearing in
      mind the different fluorescence responses observed among the dyes used here.

PMID- 10082305
TI  - Detection of hemoglobin variants in erythrocytes by flow cytometry.
AB  - BACKGROUND: With the emergence of fetal hemoglobin (Hb F)stimulating agents as
      potential treatments for sickle-cell disease and thalassemias, procedures to
      monitor the effect of these agents on Hb F levels in individuals will be needed.
      We developed a rapid procedure that detects fetal hemoglobin in erythrocytes (F
      cells) using a fluorescein isothiocyanate (FITC) conjugated monoclonal antibody
      against Hb F. METHODS: Ten microliters of washed blood was fixed in formaldehyde
      and glutaraldehyde, then permeabilized in a Triton X-100/PBS solution containing
      a FITC-labeled monoclonal antibody to Hb F. The blood was analyzed by flow
      cytometry to determine the percentage of F cells. RESULTS: Nearly 200 Hb F
      containing samples were analyzed by this protocol and demonstrated good
      correlation to percent Hb F results determined by high pressure liquid
      chromatography (HPLC). In addition, a number of samples were fixed and
      permeabilized using this method as well as a previously-described method that
      uses dimethyl 3,3'dithiobispropionimadate (DTBP) as a fixative as well as a
      different anti-Hb F monoclonal. Good correlation (r = 0.96, r2 = 0.93, P<0.001)
      was observed between the two protocols. CONCLUSIONS: This procedure is easy,
      reproducible, and gives accurate F cell results. It can be used to measure a wide
      range of F cell percentages and may also be used to dual-stain Hb F along with
      other hemoglobin variants and erythrocyte surface antigens.

PMID- 10082306
TI  - Novel technique for the direct flow cytofluorometric analysis of human basophils
      in unseparated blood and bone marrow, and the characterization of phenotype and
      peroxidase of human basophils.
AB  - BACKGROUND: No technique has been reported to analyze directly the antigen
      expression on basophil leukocytes when using a flow cytometer; therefore, the
      exact phenotype of human basophils and the character of the peroxidase in
      basophils are not well understood. METHODS: Human blood basophils were purified
      by using an antibody against high-affinity Fc epsilon receptor (hFcepsilonR) and
      a MACS magnetic cell sorting system and then cytochemically stained. The
      phenotype and peroxidase of the human basophils were flow cytofluorometrically
      analyzed directly in unseparated blood and bone marrow samples as
      hFcepsilonR+/MBP+ (major basic protein)/Hist+ (histamine) light-density cells
      distributed in the high sidescatter area of lymphocytes on light scattergrams.
      RESULTS: The peroxidase granules of human basophils were stained by an anti
      eosinophil peroxidase (EPO) antibody. The human blood basophils had common
      granulocyte markers plus CD25, i.e., they were CD11a/
      CD11b/CD11c/CD25/CD38/CD13/CD33/hFcepsi lonR/MBP/Hist/ EPO positive, CD71 dim
      positive, CD14/CD15 partially positive, and CD2/CD3/CD7/CD122/CD16/CD56/CD57/
      CD10/CD19/CD20/CD22/HLA-DR/MPO (myeloperoxidase)/CD23 negative. Further
      examination was done to analyze the expression of colony-stimulating factor
      receptors on three lineages of granulocytes, i.e., basophils, eosinophils, and
      neutrophils. The neutrophils were CD114 (G-CSFR)/CD116 (GM-CSFR)/CD124
      [interleukin (IL)-4R]/CD126 (IL-6R) positive and CD123 (IL-3R)/CD125 (IL-5R)
      negative. In contrast, the eosinophils and basophils were CD116/CD123/CD125/CD126
      positive and CD114/CD124 negative. CONCLUSIONS: This novel technique for directly
      characterizing human basophil leukocytes with flow cytometry may be a convenient
      way to screen the expression of surface antigens and the cytoplasmic expression
      of CD antigens and other proteins in human blood basophils and to analyze
      alterations of the character of basophils by cytokines and other biological
      substances in vivo and in vitro.

PMID- 10082307
TI  - Heat pretreatment increases resolution in DNA flow cytometry of paraffin-embedded
      tumor tissue.
AB  - BACKGROUND: Flow cytometry of single-cell suspensions prepared by enzymatic
      digestion from formalin-fixed, paraffin-embedded tissue suffers from several
      major drawbacks. The most important factors that influence the results are the
      high and unpredictable coefficients of variation (CVs) of the G0/G1 peak in the
      DNA histogram and reduction of propidium iodide (PI) intercalation with DNA,
      resulting from protein cross-linking by formalin. METHODS: In this study we
      introduce a heating step (2 h incubation in citrate solution at 80 degrees C)
      prior to a brief pepsin digestion of tissue sections in the protocol for DNA
      content analysis of formalin-fixed and paraffin-embedded tissue. This new method
      is compared with established methods for the preparation of cell suspensions from
      frozen and paraffin-embedded tissues with respect to cell yield, DNA histogram
      resolution, DNA dye saturation kinetics, cell cycle parameters, and antigen
      retrieval in various epithelial and nonepithelial tissues. RESULTS: The recovery
      of single cells from the paraffin sections was doubled by the heat treatment
      step, while the limited time of proteolysis resulted in decreased cell debris.
      Furthermore, an increased fraction of cells became cytokeratin-positive, while
      these immunocytochemically stained cells also exhibited a higher mean
      fluorescence intensity. The DNA histograms prepared from cell suspensions
      obtained according to this new protocol showed a significantly improved
      resolution, leading to a better identification of peridiploid cell populations.
      Heat pretreatment of paraffin-embedded archival tissue sections showed PI
      saturation kinetics similar to, or even better than, those of fresh unfixed
      tissues, independent of duration of fixation. CONCLUSIONS: This new method,
      making use of routinely available antigen retrieval principles, thus allows high
      resolution DNA analysis of routinely fixed and paraffin-embedded tissue samples.
      Using external reference cells, inter- and intralaboratory standardization of DNA
      histograms can be achieved.

PMID- 10082308
TI  - Flow cytometric detection of p53 protein after incubation of a pre-B cell line
      with antitumor agents.
AB  - BACKGROUND: The study of new substances capable of counteracting tumor
      development has focused, in recent years, on several of the steps in a cell's
      initiation of the process of apoptosis. One of the crucial events is the
      activation of p53, leading to a cell cycle G1/S block or to programmed cell
      death. METHODS: We report here a parallel flow cytometric method for
      semiquantitative detection of p53 protein and apoptosis (percent of apoptotic
      cells) in a pre-B leukemic cell line (NALM-6) exposed to various antitumor agents
      (2.35 microg/ml etoposide; 0.175 microg/ml FCE296; 0.4 microg/ml FCE624; and 1.5
      microg/ml L-PAM). RESULTS: All of the substances proved to be capable of inducing
      an increase of p53 after 16 or 24 h of incubation. In all experiments with
      antitumor agents we also found an onset of apoptosis after 24 h of incubation
      with the substance, as determined by the annexin V flow cytometric assay and by
      DNA fragmentation. CONCLUSIONS: This technique, based on flow cytometric data of
      both p53 intracellular content and percentage of apoptotic cells, is suitable to
      determine the amount of antitumor agent needed to induce p53, and thus to dose
      the drug in relation to the sensitivity of a defined tumor as well as choose the
      more efficacious drug, depending on cell responsiveness. The study of antitumor
      substances that induce apoptosis, bypassing p53, could also be evaluated by this
      method, in view of the development of substances for the treatment of p53-mutated
      tumors.

PMID- 10082309
TI  - Simultaneous detection of cyclin B1, p105, and DNA content provides complete cell
      cycle phase fraction analysis of cells that endoreduplicate.
AB  - BACKGROUND: DNA analysis of endoreduplicating cells is difficult because of the
      overlap between stem-line G2 + M cells and 4C G1 cells. Simultaneous flow
      cytometry of DNA and cyclin B1 analytically separates these populations. The
      objective here was to develop simultaneous flow cytometry of DNA, cyclin B1, and
      p105 (highly expressed in mitosis) for improved, complete cell cycle phase
      fraction analysis of endoreduplicating cell populations. METHODS: Monoclonal
      antibody, GNS-1, reactive with human cyclin B1, was conjugated with fluorescein
      at three different fluorochrome-to-protein (F/P) ratios and tested for optimal
      sensitivity in a flow cytometric assay. A formaldehyde-methanol fixation
      procedure was optimized for retention of p105 within mitotic cells by analytic
      titration of formaldehyde. p105 was stained indirectly with Cy5-conjugated
      secondary antibody, followed by GNS-1, and DNA was stained with Hoechst 33342.
      The specificity of p105 in this assay was tested by comparison of manual and flow
      cytometric mitotic indices and by sorting and microscopic inspection. RESULTS:
      F/P 4.1 provided optimal fluorescein labeling of GNS-1. Formaldehyde (0.5%),
      followed by methanol permeabilization, fixed cells sufficiently to quantify stem
      line and endoreduplicated G1, S, G2, and M phase fractions. Kinetic measurements
      of these fractions for both populations were demonstrated. CONCLUSIONS: The
      fluorochrome-to-protein ratio is important and can be optimized objectively for
      these assays. A permeabilization-sensitive antigen (p105), previously requiring
      formaldehyde/detergent-fixed cell preparations, was shown to work equally well
      with formaldehyde/ methanol fixation. Three-laser, two-parameter intracellular
      antigen analysis can be successfully coupled with DNA content analysis. Cell
      cycle kinetic analysis of endoreduplicating populations should be improved.

PMID- 10082310
TI  - Estimation of kinetic cell-cycle-related gene expression in G1 and G2 phases from
      immunofluorescence flow cytometry data.
AB  - BACKGROUND: Flow cytometry of immunofluorescence and DNA content provides
      measures of cell-cycle-related gene expression (protein and/or epitope levels)
      for asynchronously growing cells. From these data, time-related expression
      through S phase can be directly measured. However, for G1, G2, and M phases, this
      information is unavailable. We present an objective method to model G1 and G2
      kinetic expression from an estimate of a minimum biological unit of positive
      immunofluorescence derived from the distribution of specific immunofluorescence
      of mitotic cells. METHODS: DU 145 cells were stained for DNA, cyclin B1, and a
      mitotic marker (p105) and analyzed by flow cytometry. The cyclin B1
      immunofluorescence (B1) distribution of p105-positive cells was used to model the
      B1 distribution of G2 and G1 cells. The G1/S and S/G2 interface measurements were
      used to calculate expression in S phase and test the validity of the approach.
      RESULTS: B1 at S/G2 closely matched the earliest modeled estimate of B1 in G2. B1
      increased linearly through G1 and S but exponentially through G2; mitotic levels
      were equivalent to the highest G2 levels. G1 modeling of B1 was less certain than
      that of G2 due to low levels of expression but demonstrated general feasibility.
      CONCLUSIONS: By this method, the upper and lower bounds of cyclin B1 expression
      could be estimated and kinetic expression through G1, G2, and M modeled. Together
      with direct measurements in S phase, expression of B1 throughout the entire cell
      cycle of DU 145 cells could be modeled. The method should be generally applicable
      given model-specific assumptions.

PMID- 10082311
TI  - Apoptotic cell death in neurons and glial cells: implications for Alzheimer's
      disease.
AB  - It is now generally accepted that massive neuronal death due to oxidative stress
      is a common characteristic of brains in neurodegenerative diseases. Recently,
      numerous apoptosis-regulating factors and multiple pathways have been identified,
      and apoptotic cell death has been implicated in neuronal loss in Alzheimer's
      disease. Although glial cells are more resistant to oxidative stress than
      neurons, extensive oxidative stress seems to cause apoptotic cell death in glial
      cells. In fact, signs of apoptosis are observed in both neurons and glial cells
      in the brains of patients with Alzheimer's disease. This review summarizes
      current findings regarding apoptotic processes and discusses the possible
      involvement of apoptosis-regulating factors in the pathology of Alzheimer's
      disease.

PMID- 10082312
TI  - Current studies on a working model of CaM kinase II in hippocampal long-term
      potentiation and memory.
AB  - There have been recent advances in understanding the molecular basis of the long
      term potentiation (LTP) of synaptic transmission in the hippocampus. This review
      documents current views on mechanisms underlying LTP induction, from activation
      of the NMDA receptor to stimulation of Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II). We will focus in particular on recent findings of how CaM
      kinase II encodes the frequency of synaptic usage and serves as a molecular
      memory switch at the synapse. Furthermore, a role for CaM kinase II in spatial
      learning and memory is demonstrated by recent studies using transgenic mice.

PMID- 10082313
TI  - Protective effect of quinaprilat, an active metabolite of quinapril, on Ca2+
      overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes.
AB  - We examined the effects of quinaprilat, an active metabolite of quinapril (an
      angiotensin converting enzyme (ACE) inhibitor) on the increase in intracellular
      concentration of Ca2+ ([Ca2+]i) (Ca2+-overload) induced by
      lysophosphatidylcholine (LPC) in isolated rat cardiomyocytes. LPC (15 microM)
      produced Ca2+-overload with a change in cell-shape from rod to round. Quinaprilat
      but not quinapril at 20 or 50 microM attenuated the LPC-induced increase in
      [Ca2+]i and the change in cell-shape in a concentration-dependent manner. Since
      quinaprilat has an inhibitory action on ACE and quinapril has practically no
      inhibitory action on ACE, it is likely that the inhibitory action of quinaprilat
      on ACE is necessary for the protective effect of the drug against LPC-induced
      changes. We therefore examined the effects of enalapril (another ACE inhibitor
      with the weak inhibitory action on ACE) and enalaprilat (an active metabolite of
      enalapril with an inhibitory action on ACE) on the LPC-induced changes. Both
      enalapril and enalaprilat attenuated the LPC-induced Ca2+-overload, suggesting
      that the inhibitory action on ACE may not mainly contribute to the protective
      effect of ACE inhibitors against LPC-induced Ca2+-overload. This suggestion was
      supported by the fact that neither ACE (0.2 U/ml) nor angiotensin II (0.1-100
      microM) increased [Ca2+]i in isolated cardiomyocytes. Furthermore, application of
      bradykinin (0.01-10 microM) did not enhance the protective effect of quinaprilat
      against LPC-induced changes. LPC also increased release of creatine kinase (CK)
      from the myocyte markedly, and quinaprilat but not quinapril attenuated the LPC
      induced CK release. Unexpectedly, both enalapril and enalaprilat did not
      attenuate the LPC-induced CK release. Neither quinapril nor quinaprilat changed
      the critical micelle concentration of LPC, suggesting that these drugs do not
      directly bind to LPC. We conclude that quinaprilat attenuates the LPC-induced
      increase in [Ca2+]i, and that the protective effect of quinaprilat on the LPC
      induced change may not be related to a decrease in angiotensin II production or
      an increase in bradykinin production.

PMID- 10082314
TI  - Behavioral changes and cholinesterase activity of rats acutely treated with
      propoxur.
AB  - Early assessment of neurological and behavioral effects is extremely valuable for
      early identification of intoxications because preventive measures can be taken
      against more severe or chronic toxic consequences. The time course of the effects
      of an oral dose of the anticholinesterase agent propoxur (8.3 mg/kg) was
      determined on behaviors displayed in the open-field and during an active
      avoidance task by rats and on blood and brain cholinesterase activity. Maximum
      inhibition of blood cholinesterase was observed within 30 min after
      administration of propoxur. The half-life of enzyme-activity recovery was
      estimated to be 208.6 min. Peak brain cholinesterase inhibition was also detected
      between 5 and 30 min of the pesticide administration, but the half-life for
      enzyme activity recovery was much shorter, in the range of 85 min. Within this
      same time interval of the enzyme effects, diminished motor and exploratory
      activities and decreased performance of animals in the active avoidance task were
      observed. Likewise, behavioral normalization after propoxur followed a time frame
      similar to that of brain cholinesterase. These data indicate that behavioral
      changes that occur during intoxication with low oral doses of propoxur may be
      dissociated from signs characteristic of cholinergic over-stimulation but
      accompany brain cholinesterase activity inhibition.

PMID- 10082315
TI  - Hydrogen peroxide-induced apoptosis and necrosis in human lung fibroblasts:
      protective roles of glutathione.
AB  - Although reactive oxygen species (ROS)-related cell damage has been implicated in
      pathogenesis of fibrogenetic pulmonary disorders, features of ROS-mediated cell
      death in human lung fibroblasts are not completely understood. We therefore
      examined the effects of hydrogen peroxide (H2O2) on cell growth kinetics in human
      lung fibroblasts (HFL-1 cells) and tested the roles of antioxidants on the H2O2
      induced cell death (i.e., necrosis and apoptosis) in HFL-1 cells. We found that
      the relatively low concentrations of H2O2 ranging from 10 microM to 100 microM
      induced predominantly apoptosis, whereas higher concentration of H2O2 ranging 1
      mM-10 mM induced predominantly necrosis in HFL-1 cells. Extracellular
      supplementation of glutathione (GSH) in culture media significantly abolished the
      H2O2-induced cell death, whereas GSH-depleted cells by pretreatment with
      buthionine sulfoxime (BSO) were likely to undergo cell death caused by a lower
      concentration of H2O2 than normal HFL-1 cells without BSO treatment. These
      results indicate that H2O2 induces both necrosis and apoptosis of human lung
      fibroblasts at least in part through the action of ROS and that modulation of the
      ROS production inside and outside of cells may influence the cell survival during
      oxidative insults.

PMID- 10082316
TI  - Regional and functional differences of 5-hydroxytryptamine-receptor subtypes in
      guinea pig stomach.
AB  - Functions and the presence of 5-hydroxytryptamine (5-HT) receptors in the fundus,
      corpus and antrum of the guinea pig stomach were examined by measuring
      contractile force and acetylcholine (ACh) release. Stimulation of the 5-HT1
      receptor caused tetrodotoxin (TTX)-insensitive relaxations in the preparations
      from 3 regions. Stimulation of the 5-HT2 receptor caused TTX-insensitive
      contractions in the preparations of fundus and antrum. Stimulation of 5-HT3
      receptors caused contractions that were sensitive to TTX and atropine and
      enhanced the outflow of [3H]ACh from preparations of only antrum. Stimulation of
      5-HT4 receptors caused contractions of antral strips and decreased relaxations of
      corporal strips and enhanced the outflow of [3H]ACh from the preparations of both
      corpus and antrum. In the guinea pig stomach, the fundus possesses relaxant 5-HT1
      receptor < contractile 5-HT2 receptors and caused the contractile response to 5
      HT. The corpus possesses relaxant 5-HT1 receptors and relaxant receptors other
      than 5-HT1, 5-HT2, 5-HT3 and 5-HT4 receptors > contractile 5-HT4 receptor, and
      therefore 5-HT caused relaxations. The antrum possesses relaxant 5-HT1 receptor <
      contractile 5-HT2, 5-HT3 and 5-HT4 receptors, and thus 5-HT caused contractions.

PMID- 10082317
TI  - Effects of nicorandil on experimentally induced gastric ulcers in rats: a
      possible role of K(ATP) channels.
AB  - The anti-ulcer effects of nicorandil [N-(2-hydroxyethyl)nicotinamide nitrate
      ester] were examined on water-immersion plus restraint stress-induced and aspirin
      induced gastric ulcers in rats, compared with those of cimetidine. Nicorandil (3
      and 10 mg/kg) given orally to rats dose-dependently inhibited the development of
      acid-related damage (water-immersion- and aspirin-induced gastric lesions) in the
      models. Cimetidine (50 mg/kg, p.o.) also had anti-ulcer effects in the same
      models. However, in the presence of glibenclamide (20 mg/kg, i.v.), an antagonist
      of K(ATP) channels, nicorandil did not inhibit the formation of gastric lesions.
      Nicorandil (10 mg/kg) given intraduodenally (i.d.), like cimetidine (50 mg/kg),
      significantly reduced the volume of the gastric content, total acidity and total
      acid output in the pylorus ligation model. Glibenclamide reversed the changes
      caused by i.d. nicorandil. I.v. infusion of nicorandil (20 microg/kg per min)
      significantly increased gastric mucosal blood flow, without affecting blood
      pressure and heart rate, but the increase in the blood flow was not observed
      after i.v. treatment with glibenclamide (20 mg/kg). These results indicate that
      nicorandil administered orally to rats produces the anti-ulcer effect by reducing
      the aggressive factors and by enhancing the defensive process in the mucosa
      through its K(ATP)-channel-opening property.

PMID- 10082318
TI  - ATP-sensitive potassium channels regulate in vivo dopamine release in rat
      striatum.
AB  - ATP-sensitive K+ channels (K(ATP)) are distributed in a variety of tissues
      including smooth muscle, cardiac and skeletal muscle, pancreatic beta-cells and
      neurons. Since K(ATP) channels are present in the nigrostriatal dopamine (DA)
      pathway, the effect of potassium-channel modulators on the release of DA in the
      striatum of conscious, freely-moving rats was investigated. The extracellular
      concentration of DA was significantly decreased by the K(ATP)-channel opener (-)
      cromakalim but not by diazoxide. (-)-Cromakalim was effective at 100 and 1000
      microM concentrations, and the maximum decrease was 54% below baseline. d
      Amphetamine significantly increased extracellular DA levels at the doses of 0.75
      and 1.5 mg/kg, s.c. with a 770% maximum increase. (-)-Cromakalim had no effect on
      d-amphetamine-induced DA release, while glyburide, a K(ATP) blocker,
      significantly potentiated the effects of a low dose of d-amphetamine. These data
      indicate that K+ channels present in the nigrostriatal dopaminergic terminals
      modulate basal release as well as evoked release of DA.

PMID- 10082319
TI  - The novel analgesic compound OT-7100 (5-n-butyl-7-(3,4,5
      trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimid ine) attenuates mechanical
      nociceptive responses in animal models of acute and peripheral neuropathic
      hyperalgesia.
AB  - We investigated the effects of OT-7100, a novel analgesic compound (5-n-butyl-7
      (3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a]pyrimidi ne), on prostaglandin E2
      biosynthesis in vitro, acute hyperalgesia induced by yeast and substance P in
      rats and hyperalgesia in rats with a chronic constriction injury to the sciatic
      nerve (Bennett model), which is a model for peripheral neuropathic pain. OT-7100
      did not inhibit prostaglandin E2 biosynthesis at 10(-8)-10(-4) M. Single oral
      doses of 3 and 10 mg/kg OT-7100 were effective on the hyperalgesia induced by
      yeast. Single oral doses of 0.1, 0.3, 1 and 3 mg/kg OT-7100 were effective on the
      hyperalgesia induced by substance P in which indomethacin had no effect. Repeated
      oral administration of OT-7100 (10 and 30 mg/kg) was effective in normalizing the
      mechanical nociceptive threshold in the injured paw without affecting the
      nociceptive threshold in the uninjured paw in the Bennett model. Indomethacin had
      no effect in this model. While amitriptyline (10 and 30 mg/kg) and clonazepam (3
      and 10 mg/kg) significantly normalized the nociceptive threshold in the injured
      paw, they also increased the nociceptive threshold in the uninjured paw. These
      results suggest that OT-7100 is a new type of analgesic with the effect of
      normalizing the nociceptive threshold in peripheral neuropathic hyperalgesia.

PMID- 10082320
TI  - Effect of the hypocholesterolemic agent YM-16638 on cholesterol biosynthesis
      activity and apolipoprotein B secretion in HepG2 and monkey liver.
AB  - YM-16638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl]thio]-1,3,4-++
      +thiadiazol-2-yl] thio] acetic acid) showed a strong hypocholesterolemic effect
      in humans and monkeys. To clarify the mechanism of this hypocholesterolemic
      effect, the action of YM-16638 on cholesterol biosynthesis in the cultured human
      hepatoma cell line HepG2 and cynomolgus monkey liver was examined. Cholesterol
      biosynthesis activity derived from [14C]acetic acid, [3H/14C]mevalonic acid or
      [14C]isopentenyl pyrophosphate substrates was significantly decreased, but not
      that from [3H]farnesyl pyrophosphate or [3H]squalene substrates in HepG2 cells
      treated with YM-16638. Simultaneously, treatment of these cells with YM-16638
      changed neither the rate of apolipoprotein B synthesis from [35S]methionine nor
      its secretion. In addition, the activities of hepatic cholesterol biosynthesis
      enzymes HMG-CoA reductase, mevalonate kinase (MK), isopentenyl pyrophosphate
      isomerase (IPPI), farnesyl pyrophosphate synthase (FPPS), squalene synthase and
      squalene epoxidase were measured in monkeys fed a diet supplemented with YM
      16638. Among these enzymes, MK, IPPI and FPPS activities in the YM-16638-treated
      group significantly decreased by 38%, 56% and 30%, respectively, when compared to
      those from control animals receiving no drug treatment. These results indicate
      that YM-16638 has the characteristics of a cholesterol biosynthesis inhibitor.

PMID- 10082321
TI  - Characterization of socio-psychological stress-induced antinociception in the
      formalin test in mice.
AB  - The antinociceptive effect induced by exposure to socio-psychological (PSY)
      stress using a communication box was assessed by the formalin test in mice,
      compared with those by exposure to footshock (FS) stress and forced swimming (SW)
      stress. After the termination of stress exposure, whereas exposure to FS- and SW
      stress resulted in the attenuation of the formalin-induced biphasic pain response
      over 15 min, no appreciable antinociceptive effect was found in the case of PSY
      stress. When exposure to PSY stress was started during the period of early or
      late phase of pain after the formalin injection, the antinociceptive effect was
      maintained for 5-15 min; however, further exposure to PSY stress was not
      effective for producing antinociception. In the tail-pinch test, likewise,
      exposure to PSY stress longer than 5 min rather decreased the intensity of
      antinociception. We conclude that PSY stress in this tonic pain paradigm produces
      antinociception, but further continuous exposure to the emotional stress caused
      mice to become recuperative even in such a fear-inducing situation.

PMID- 10082322
TI  - Inhibition of protein denaturation by fatty acids, bile salts and other natural
      substances: a new hypothesis for the mechanism of action of fish oil in rheumatic
      diseases.
AB  - Natural hydrophobic substances like bile salts (cholate, deoxycholate,
      chenodeoxycholate, lithocholate and their conjugates with glycine and taurine),
      fatty acids (caprylic, capric, lauric, myristic, palmitic, stearic, oleic,
      linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acid) were much more
      active (EC50 approximately 10(-4)-10(-5) M) than selected amino acids (EC50 > 10(
      2) M) and inorganic salts (EC50 approximately 10(-1) M) in inhibiting heat
      induced denaturation of human serum albumin in vitro. Fish oil, rich in n-3
      polyunsaturated acids such as eicosapentaenoic acid and docosahexaenoic acid,
      administered p.o. (1 ml/kg) in the rat, protected ex vivo (after 2 hr) serum
      against heat-induced denaturation more than bendazac, a known antidenaturant
      drug. Thus, we speculated that the antidenaturant activity of fish oil may be
      partly (in addition to the known effect on endogenous eicosanoid composition)
      responsible for its beneficial effects in rheumatoid arthritis and other
      rheumatic conditions. In this connection, it is of note that the in vitro
      antidenaturant activity of fish oil fatty acids was higher than that of known
      antidenaturant drugs such as bendazac and bindarit and nonsteroidal anti
      inflammatory drugs like phenylbutazone and indomethacin which could exert
      beneficial effects in chronic inflammatory conditions by stabilizing endogenous
      proteins.

PMID- 10082323
TI  - Role of thromboxane A2 in healing of gastric ulcers in rats.
AB  - We investigated the role of thromboxane (TX) A2 in gastric ulcer healing in rats.
      Acetic acid ulcers were produced in male Donryu rats. TXA2 synthesis in the
      stomachs with ulcers was significantly elevated in ulcerated tissue, but not in
      intact tissue, compared with that in the gastric mucosa of normal rats.
      Indomethacin inhibited both TXA2 and prostaglandin E2 (PGE2) synthesis in
      ulcerated tissue, while NS-398 (selective cyclooxygenase-2 inhibitor) reduced
      only PGE2 synthesis. OKY-046 (TXA2 synthase inhibitor) dose-relatedly inhibited
      only TXA2 synthesis. The maximal effect of OKY-046 (80% inhibition) was found at
      more than 30 mg/kg. When OKY-046 was administered for 14 days, the drug at more
      than 30 mg/kg significantly accelerated ulcer healing without affecting acid
      secretion. The maximal reduction of ulcerated area by OKY-046 was about 30%,
      compared with the area in the control. Histological studies revealed that
      regeneration of the mucosa was significantly promoted by OKY-046, but neither
      maturation of the ulcer base nor angiogenesis in the base were affected. OKY-046
      and TXB2 had no effect on proliferation of cultured rat gastric epithelial cells,
      but U-46619 (TXA2 mimetic) dose-relatedly prevented the proliferation without
      reducing cell viability. These results indicate that the increased TXA2, probably
      derived from cyclooxygenase-1 in ulcerated tissue, exerts a weak inhibitory
      effect on ulcer healing in rats. The effect of TXA2 might be due partly to
      prevention of gastric epithelial cell proliferation at the ulcer margin.

PMID- 10082324
TI  - In vivo microdialysis assessment of nerve-stimulated contractions associated with
      increased acetylcholine release in the dog intestine.
AB  - Intestinal contractility and release of endogenous acetylcholine (ACh) were
      measured simultaneously in vivo in the small intestine of the anesthetized dog.
      Electrical stimulation of nerves in the intestinal seromuscular layers caused
      contractions and increased concentrations of ACh in the dialysate, which were
      abolished by infusion of tetrodotoxin into the intestinal marginal artery at 75
      nmol/ml. Intraarterial administration of atropine at 150 nmol/ml abolished the
      stimulated contractions, without significant effects on increases in
      concentrations of dialysate ACh. Thus, the nerve-stimulated contractions were
      found in vivo to be associated with a local increase in ACh release from the
      intestinal cholinergic neurons.

PMID- 10082325
TI  - Central nervous system-mediated hyperglycemic effects of NIK-247, a
      cholinesterase inhibitor, and MKC-231, a choline uptake enhancer, in rats.
AB  - We investigated the effects of intracerebroventricular administration of NIK-247
      (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclo-penta(b)-quinoline monohydrate
      hydrochloride; a cholinesterase inhibitor) or MKC-231 (2-(2-oxypyrrolidin-1-yl)-N
      (2,3-dimethyl-5,6,7,8-tetrahydrofur o[2,3-b]quinolin-4-yl) acetoamide; a choline
      uptake enhancer) on plasma glucose level in comparison with that of neostigmine
      administration in rats. The extents of NIK-247- and MKC-231-induced hyperglycemia
      were considerably less than that by neostigmine, suggesting that the potencies of
      the drugs to produce the peripheral hyperglycemia may be pharmacologically
      negligible.

PMID- 10082326
TI  - Identification of kallidin degrading enzymes in the isolated perfused rat heart.
AB  - Kallidin (KD) is an important vasoactive kinin whose physiological effects are
      strongly dependent on its degradation through local kininases. In the present
      study, we examined the spectrum of these enzymes and their contribution to KD
      degradation in isolated perfused rat hearts. By inhibiting angiotensin-converting
      enzyme (ACE), aminopeptidase M (APM) and neutral endopeptidase (NEP) with
      ramiprilat (0.25 microM), amastatin (40 microM) and phosphoramidon (1 microM),
      respectively, relative kininase activities were obtained. APM (44%) and ACE (35%)
      are the main KD degrading enzymes in rat heart; NEP (7%) plays a minor role. A
      participation of carboxypeptidase N (CPN) could not be found.

PMID- 10082327
TI  - Cytotoxic effect of paraquat on rat C6 glioma cells: evidence for the possibility
      of non-oxidative damage to the cells.
AB  - Although paraquat has been shown to cause oxidative damage to neuronal cells,
      little is known about its effect on glial cells. Thus the effect of paraquat on
      glial cells was examined using rat C6 glioma cells as a model system. Paraquat
      reduced cell viability in a concentration- and time-dependent manner, and this
      toxic effect was not significantly attenuated by various kinds of antioxidants.
      Furthermore, paraquat failed to increase 8-hydroxy-deoxyguanosine formation in
      the cells. These results indicate that paraquat can be toxic to glial cells and
      suggest that this cytotoxic effect may not be associated with the oxidative
      damage to the cells.

PMID- 10082328
TI  - Hemispheric and sex-linked differences in Sylvian fissure morphology: a
      quantitative approach using volumetric magnetic resonance imaging.
AB  - OBJECTIVE: In a sample of right-handed adults, volumetric magnetic resonance
      imaging (MRI) was used to reinvestigate hemispheric and sex-linked differences in
      Sylvian fissure (SF) morphology. BACKGROUND: Asymmetries of the SF exist with a
      predominant leftward asymmetry consistently reported in postmortem studies. These
      anatomic asymmetries may reflect asymmetric allocation of adjacent opercula, with
      some investigators positing a relationship with planum temporale asymmetries, as
      the postcentral SF is more asymmetric than the anterior segment. Sex-related
      differences have also been reported with reduced asymmetries in women relative to
      men. METHOD: Using in vivo MRI surface renderings, SF asymmetries were studied in
      a group of consistently right-handed men (n = 12) and women (n = 12). Anterior
      and postcentral SF lengths were measured. RESULTS: Overall, there was a
      significant leftward asymmetry of the horizontal SF (anterior and postcentral) in
      men and women. Whereas there was a significant leftward asymmetry of the
      postcentral SF, there was no significant asymmetry of the anterior SF. There was
      an increase in the parietal operculum anterior to the posterior ascending ramus
      (PAR) in the left hemisphere and posterior to the PAR in the right hemisphere
      when SF asymmetries were leftward, with the length of the anterior parietal
      operculum positively correlated with postcentral SF length. CONCLUSIONS: These
      findings demonstrate that the SF is asymmetric but that clear sex-related effects
      do not exist in consistently right-handed subjects.

PMID- 10082329
TI  - Psychophysical and electrophysiologic support for a left hemisphere temporal
      processing advantage.
AB  - OBJECTIVE: The objective of this study was to investigate cerebral asymmetries
      for the detection of brief temporal events in a group of 22 dextrals using
      psychophysical measures. BACKGROUND: By combining electrophysiologic and
      psychophysical measures, it should be possible to demonstrate that the right ear
      advantage reported in previous studies is the result of a left hemisphere
      temporal processing advantage rather than a rightward attentional bias. METHOD:
      Bursts of white noise lasting 300 milliseconds were delivered unilaterally to the
      participants' ears. Half of the stimuli contained a gap lasting either 4 or 6
      milliseconds. Participants indicated whether or not the noise burst contained a
      gap. Asymmetries in alpha and beta activity at left and right temporal lobe sites
      were measured during the task. RESULTS: The psychophysical data confirmed
      previous reports of faster response times (RTs) and lower levels of error for the
      right ear (RE). There was no asymmetry in alpha activity between the left and
      right temporal lobes; however, there was a higher level of beta activity in the
      left temporal lobe. CONCLUSIONS: The electrophysiological data suggest that the
      perceptual asymmetry is not the result of a nonspecific rightward attentional
      bias but that of a left hemisphere specialization for the detection of brief
      temporal events. The relation between atypical temporal processing asymmetries
      and developmental learning disorders is discussed.

PMID- 10082330
TI  - Possible roles for mismatch negativity in neuropsychiatry.
AB  - OBJECTIVE: This article reviews research on the main characteristics of mismatch
      negativity (MMN) and its applications in neuropsychiatry. BACKGROUND: Event
      related potentials (ERPs) have been used to study many aspects of information
      processing. Mismatch negativity is an early auditory ERP that has been identified
      as an index of an automatic (preconscious) alerting mechanism stimulating an
      individual to attend to unexpected environmental events. Disturbances of MMN may
      relate to abnormalities of auditory information processing contributing to the
      pathophysiology of neuropsychiatric conditions. METHOD: The authors review (1)
      studies that have evaluated the electrophysiological aspects of MMN and (2)
      studies that have investigated the different applications of MMN in
      neuropsychiatry. RESULTS: The first part of this article describes the
      characteristics of MMN, its cerebral origins, and electrophysiological
      parameters. We then discuss the role of "echoic memory" as well as that of
      attention and vigilance. In the second part of the article, disturbances in MMN
      associated with schizophrenia, depressive illness, dementing processes, and other
      neuropsychiatric states are discussed. CONCLUSIONS: MMN is a preconscious
      cognitive ERP, the main generators and functions of which are well defined.
      Observations relating to the origins of MMN and its role in early auditory
      information processing together with its possible behavioral significance,
      combined with observations of MMN aberrations in psychiatric conditions, may
      provide novel insights into the pathophysiology of neuropsychiatric states.

PMID- 10082331
TI  - Age effects on random-array letter cancellation tests.
AB  - OBJECTIVE: This study was designed to determine whether young and older adults
      differ in the spatial pattern of omission errors on random-array letter
      cancellation tasks. BACKGROUND: Aging is associated with declines in the speed or
      efficiency of visual information processing. It is unclear whether the spatial
      characteristics of visual exploration also change with aging. METHOD: Thirty
      young adults and 30 older adults each completed 21 random-array cancellation
      forms. Forms were systematically varied in paper size, target-to-distractor
      ratio, stimulus density, and target number. RESULTS: The spatial distribution of
      errors was not random for older adults. Younger adults expressed a trend toward
      nonrandom error location, but the spatial distribution did not differ between
      groups. There was also a strong trend toward more errors per subject in the older
      group. Older subjects required more time for task completion. CONCLUSIONS: The
      findings are consistent with a generalized age-related decline in the speed or
      efficiency of visual search, but the spatial properties of directed attention do
      not appear to be different between young and older adults.

PMID- 10082332
TI  - Mania, pseudomania, depression, and pseudodepression resulting from focal
      unilateral cortical lesions.
AB  - OBJECTIVE: This consecutive multiple case study was designed to determine whether
      cortical lesion sites can predict occurrence of mood or psychomotor disorders in
      adults and children. BACKGROUND: Most of a large body of research supports the
      contention that left hemisphere lesions result more often than right ones in
      depression, and that the inverse occurs in mania. However, it is not clear how
      psychomotor status fits into this picture, nor whether children respond to the
      same lesions in a similar manner. METHOD: Published (n = 88) and unpublished (n =
      31) cases of school-aged child and adult patients with focal unilateral cortical
      lesions and psychomotor agitation or lethargy with or without corresponding mania
      or depression were reviewed systematically to determine whether lesion location
      relates systematically to any of those psychiatric conditions. No patients had
      symptoms prior to detection of their lesion. Manic-depressives and agitated
      depressives were also excluded. RESULTS: Patients with mania and/or psychomotor
      agitation had predominantly right hemisphere lesions. Postlesion hyperactivity
      (without mania) in children was common but was not more related to lesions in one
      or the other hemisphere. Adult and child patients with depression and/or
      psychomotor lethargy had predominantly left hemisphere lesions. The
      intrahemispherical site of the lesion did not significantly predict the type of
      mood or psychomotor disorder. Nevertheless, the nonsignificant trend was for
      right posterorolandic lesions to predict mania or agitation and for left frontal
      lesions to predict depression or psychomotor lethargy. CONCLUSIONS: These
      findings support the neuropsychiatric approach to mood and psychomotor disorder
      in children and adults.

PMID- 10082333
TI  - Vulnerability to emotionally negative stimuli in Parkinson's disease: an
      investigation using the Emotional Stroop task.
AB  - OBJECTIVE: The objective of this study was to determine whether the
      pathophysiological changes associated with Parkinson's disease (PD) lead to an
      increased vulnerability to react to negative emotional stimuli and hence to
      depression. It is hypothesized that nondepressed PD patients will demonstrate,
      associated with particular PD and/or cognitive variables, vulnerability to the
      interfering effects of negative words on the Emotional (sad) Stroop task (EST).
      BACKGROUND: Depression has been reported to occur frequently in PD, but there is
      controversy regarding its pathophysiology: psychosocial factors versus
      neurobiologic ones. METHOD: Thirty nondepressed/ nondemented patients with
      idiopathic PD attending a specialist movement disorders clinic were assessed from
      their emotional state (Beck's Depression Inventory [BDI], and Hospital Anxiety
      and Depression Scale) and from their cognitive state (Mini-Mental State
      Examination, Stroop tasks [including the EST], Modified Card Sorting Test, Word
      Fluency tasks, Digit Span, and Trail Making tests). In addition, information was
      gathered on PD-related variables such as severity (Hoehn and Yahr scale),
      duration of the disease, and type of motor response to dopaminergic drugs. The
      sample was split into two groups according to the median BDI score to allow for
      comparisons. One-way ANOVA techniques were used to look for significant
      differences between variables in the two groups. Bivariate correlations were used
      to look for significant relationships between variables in each group. RESULTS:
      The two groups only differed in parameters measuring emotional state. Only the
      subjects with higher BDI scores showed significant correlations between EST
      performance and cognitive and PD-related variables. CONCLUSIONS: Those PD
      patients with more severe forms of illness and a greater level of prefrontal
      cognitive dysfunction are more vulnerable to the distracting effects of external
      negative stimuli. According to the cognitive model of depression, this may
      ultimately lead to the development of clinical depression.

PMID- 10082334
TI  - Mechanisms underlying diminished novelty-seeking behavior in patients with
      probable Alzheimer's disease.
AB  - OBJECTIVE: To better understand apathy and disengagement in patients with
      Alzheimer's disease (AD), the authors investigated possible behavioral mechanisms
      underlying diminished novelty-seeking activity in patients with probable AD.
      BACKGROUND: Apathy and disengagement have been shown to be the most common
      behavioral changes associated with AD. METHOD: Patients and age-matched normal
      controls had their eye movements recorded while pairs of line drawings pitting an
      incongruous figure against a congruous figure were shown on a screen for 12
      seconds. Characteristics of a subset of AD patients who were indifferent to novel
      visual stimuli as measured by exploratory eye movements were compared to those of
      a subset of AD patients who were attracted to novel stimuli to a degree similar
      to that of normal controls. RESULTS: The indifferent patients were judged by
      informants, who completed a personality questionnaire, to exhibit a greater
      degree of apathy. The two AD groups did not differ in overall dementia severity
      or performance on a Saccade-to-Target Task that required shifts of attention and
      gaze. In a separate task, the indifferent patients were able to accurately
      identify the more novel stimuli in 97.5% of trials. Normal control subjects
      exhibited a strong bias toward processing novel stimuli, directing a higher
      proportion of their first fixations and dwell time to the incongruous stimuli
      whether the analysis was run for 3, 6, or 12 seconds of viewing. Indifferent
      patients did not direct their initial fixation toward novel stimuli and
      distributed their looking time evenly between incongruous and congruous stimuli
      throughout all measured intervals. CONCLUSIONS: The results suggest that the
      indifference to novelty observed in some patients with probable AD cannot simply
      be attributed to global cognitive decline, more elementary attentional deficits,
      more rapid habituation of response to novel stimuli, or an inability to
      discriminate upon demand between stimuli of varying degrees of novelty. It is
      more likely that their behavior reflects a disruption, by AD pathology, of neural
      systems that modulate behavioral engagement and maintain attentional bias toward
      novel events in the environment.

PMID- 10082335
TI  - Hallucinatory experiences in extreme-altitude climbers.
AB  - OBJECTIVE: This study attempted a systematic investigation of incidence, type,
      and circumstances of anomalous perceptual experiences in a highly specialized
      group of healthy subjects, extreme-altitude climbers. BACKGROUND: There is
      anecdotal evidence for a high incidence of anomalous perceptual experiences
      during mountain climbing at high altitudes. METHOD: In a structured interview, we
      asked eight world-class climbers, each of whom has reached altitudes above 8500 m
      without supplementary oxygen, about hallucinatory experiences during mountain
      climbing at various altitudes. A comprehensive neuropsychological,
      electroencephalographic, and magnetic resonance imaging evaluation was performed
      within a week of the interview (8). RESULTS: All but one subject reported
      somesthetic illusions (distortions of body scheme) as well as visual and auditory
      pseudohallucinations (in this order of frequency of occurrence). A
      disproportionately large number of experiences above 6000 m as compared to below
      6000 m were reported (relative to the total time spent at these different
      altitudes). Solo climbing and (in the case of somesthetic illusions) life
      threatening danger were identified as probable triggers for anomalous perceptual
      experiences. No relationship between the number of reported experiences and
      neuropsychological impairment was found. Abnormalities in electroencephalographic
      (3 climbers) and magnetic resonance imaging (2 climbers) findings were likewise
      unrelated to the frequency of reported hallucinatory experiences. CONCLUSIONS:
      The results confirm earlier anecdotal evidence for a considerable incidence of
      hallucinatory experiences during climbing at high altitudes. Apart from hypoxia,
      social deprivation and acute stress seem to play a role in the genesis of these
      experiences.

PMID- 10082336
TI  - Cognitive processing speed in Lyme disease.
AB  - OBJECTIVE: The goal of this study was to more precisely define the nature of the
      cognitive processing deficits in the patients with Lyme disease. BACKGROUND: Lyme
      disease has been associated with cognitive disturbances. METHOD: Sixteen patients
      who met the Centers for Disease Control's case definition for Lyme disease and 15
      age- and education-matched control subjects completed two computerized
      assessments. The first was a matching procedure that assessed perceptual/motor
      speed. The second task was an alphabet-arithmetic (AA) test that measured the
      speed of mental arithmetic. On the matching task, subjects judged as true or
      false simple identity equations (e.g., B + 0 = B). On the AA task, subjects
      indicated the veracity of equations of the same form as those of the matching
      task but which required mental arithmetic (e.g., A + 3 = D). The use of this
      paradigm permits sensory or motor slowing to be distinguished from slowed
      cognitive processing speed. Also, the tests do not involve automated or
      overlearned responses. RESULTS: Lyme disease patients and healthy controls did
      not differ in perceptual/motor speed. However, Lyme disease patients' response
      times were significantly longer than those of healthy controls during the AA
      task, demonstrating specific impairments in mental activation speed. CONCLUSIONS:
      These results suggest that Lyme disease patients show specific deficits when
      initiating a cognitive process. These impairments are independent of sensory,
      perceptual, or motor deficits.

PMID- 10082337
TI  - Vigabatrin in the treatment of infantile spasms.
AB  - Infantile spasms (IS) have been conventionally treated with adrenocorticotropic
      hormone (ACTH), which is often associated with significant side effects. This
      study assessed the efficacy of vigabatrin (VGB) as an alternative in the
      treatment of IS and compared the efficacy of VGB in symptomatic vs cryptogenic
      patients. The study retrospectively reviewed 25 infants with IS (19 symptomatic,
      six cryptogenic) who were treated with VGB. Of the symptomatic group, 13 (68.4%)
      of 19 had clinical improvement, and 15 (78.9%) had electroencephalographic
      improvement. Three (50%) of six in the cryptogenic group had clinical
      improvement, and two (33%) had electroencephalographic improvement. Overall,
      three patients demonstrated clinical spasm control but electroencephalographic
      deterioration or persistence of hypsarrhythmia coupled with further cognitive
      decline. Four of the six partial clinical responders had deterioration of spasms
      with additional VGB dosage increases. VGB is comparable with ACTH in
      effectiveness for treatment of symptomatic IS. Higher doses of VGB may sometimes
      cause deterioration rather than further improvement, and therefore an optimum
      dosage of VGB needs to be titrated for every patient. Persistent
      electroencephalographic abnormalities and even electroencephalographic
      deterioration despite clinical control have been observed with VGB treatment;
      electroencephalographic monitoring during VGB treatment is recommended.

PMID- 10082338
TI  - Clinical significance of plantar grasp response in infants.
AB  - The present study was undertaken to delineate the clinical significance of the
      plantar grasp response in infants. All 834 normal control infants had a positive
      response within the first 6 months of age, and most of them had a marked response
      at 1-4 months of age. The authors attempted to evaluate the neurologic outcomes
      of infants who had negative or diminished responses in these respective periods.
      Ninety-three infants examined from 1982 to 1992 fulfilled these criteria, and
      their prognoses were reviewed. The outcomes consisted of cerebral palsy in 75 (69
      spastic, four athetoid with spasticity, one athetoid, and one ataxic); mental
      retardation in seven; borderline intelligence in two; motor delay in one; and
      eight were considered normal. These outcomes indicate that the negative or
      diminished response of this primitive reflex during early infancy is highly
      suggestive of neurologic abnormalities, especially for spasticity. Infants with
      such findings should be carefully observed for possible development of neurologic
      abnormalities.

PMID- 10082339
TI  - Use of the pediatric symptom checklist in the pediatric neurology population.
AB  - The purpose of this study was to evaluate the effectiveness of the Pediatric
      Symptom Checklist (PSC) as a mental health screening instrument in a busy
      pediatric neurology population in comparison with more lengthy, time-consuming
      assessment methods. One hundred two children were screened using the PSC. PSC
      results were compared with scores on the Child Behavior Checklist (CBCL), results
      from structured interviews, and ratings of adaptive functioning using the
      Children's Global Assessment Scale (CGAS). Thirty-nine of the patients (38%)
      scored 63 or above on the CBCL, indicating psychosocial impairment. Using a
      cutoff score of 22, the PSC correctly identified 35 of these 39 positive cases
      (sensitivity 89.7) and 48 of the 63 children with CBCL scores below 63
      (specificity 76.2). CGAS scores were significantly negatively correlated with PSC
      scores (r = -0.60, P < 0.05). The PSC correctly identified 85.9% of children who
      scored 70 or below on the CGAS. Among the 53 children with psychiatric diagnoses
      on the basis of the interview, 41 scored above the cutoff of 22 on the PSC.
      Results suggest that the PSC is an efficient and accurate screen for
      identification of mental health problems in the pediatric neurology population.

PMID- 10082340
TI  - Neurologic consultations in children with systemic cancer.
AB  - The frequency and severity of neurologic symptoms in children with systemic
      cancer is unknown. The authors reviewed the records of children with systemic
      cancer for whom a neurologic consultation was requested between 1993 and 1996.
      The 157 patients had 161 malignancies and 205 consultations. Leukemia (59) and
      lymphoma (34) were the most common malignancies. The 68 solid tumors included
      neuroblastoma (13), Ewing's sarcoma, and rhabdomyosarcoma (10 each). In contrast
      to adults, in whom back pain and altered mental status are the most common
      reasons for neurologic consultation, headache (33) and seizures (29) were the
      most common symptoms in children. Structural lesions were present in 84% of
      patients with headache and focal deficit and in 14% of patients with isolated
      headache. Structural disease was identified in 37% of children with seizures.
      Neurologic signs were caused by complications of cancer therapy in 70 instances
      and to direct tumor invasion of the nervous system in 60. In 71 consultations,
      neurologic symptoms could not be attributed to cancer or its treatment. The
      spectrum of neurologic symptoms in children with cancer differs from adults and
      requires the consulting neurologist to have a thorough knowledge of childhood
      cancer and its effects on the nervous system.

PMID- 10082341
TI  - Organ growth in Rett syndrome: a postmortem examination analysis.
AB  - Rett syndrome is a disorder of unknown etiology in females that manifests as
      severe mental and motor retardation during the first years of life. A postnatal
      pattern of altered growth is its earliest clinical expression. Head growth
      decelerates during the first year of age and is followed by a decline in somatic
      (height/weight) growth. The decreased occipitofrontal circumference (OFC) is
      reflected in decreased brain size, and measurements of the dendrites of cortical
      neurons suggest that a developmental and growth arrest have occurred. To further
      document growth in Rett syndrome, measurements of organ weights, as recorded in
      39 postmortem examination studies were compared with normal organ weights for
      females of comparable age and height. These organ weights suggest that the
      pattern of growth failure in Rett syndrome, as compared with other forms of
      mental handicap, such as Down syndrome and Turner's syndrome, may be unique. In
      Rett syndrome the rate of brain growth, as derived from OFC, decelerates after
      birth. The increment in normal brain weight after 4 years of age, the age of the
      first postmortem examinations, is not observed in the Rett brain. The heart,
      kidneys, liver, and spleen grow at the normally defined rate until 8-12 years of
      age, when their growth rate decelerates, but their growth continues achieving
      organ weights that are appropriate for the height of the female. Adrenal weights
      are normal. These observations suggest that despite a generalized decreased
      growth in Rett syndrome the brain may be preferentially affected in this
      syndrome.

PMID- 10082342
TI  - Progressive sensorineural hearing loss in childhood.
AB  - A progressive sensorineural hearing loss in childhood, with an extremely variable
      prevalence (from 4% to 30%), has been reported in the literature. This wide range
      of reported figures could depend on the different criteria used for identifying
      the deterioration, the groups, and the examined age ranges. The most frequent
      etiology of progressive sensorineural hearing loss in childhood includes
      hereditary causes, both syndromic and nonsyndromic, and developmental and
      infectious causes, whereas metabolic, toxic, autoimmune, traumatic, and vascular
      etiologies are less common; however, the origin of the hearing impairment often
      remains unknown. The population for this study consisted of 178 children with
      bilateral sensorineural hearing loss who were examined between 1971 and 1993
      using audiologic tests. Syndromal genetic hearing loss was excluded from the
      study. A progressive loss of acuity was found in 11 subjects, with a prevalence
      of 6.2%. The etiology was hereditary deafness in five patients, congenital
      infection in one, and congenital inner ear anomaly in another patient; in the
      last four children the etiology was unknown. Onset of deterioration was after 4
      years of age in 73% of the patients. The progressive evolution was binaural in
      almost all patients (10 of 11) and asymmetric in most, with a tendency to a
      greater deterioration at the frequencies initially least affected.

PMID- 10082343
TI  - Cerebrospinal nerve growth factor--a marker of asphyxia?
AB  - Asphyxia in neonates is characterized by different degrees of hypoxia-ischemia,
      with the outcome depending on the severity of the underlying brain cell damage.
      Neurotrophic factors rescue neurons from cell death after injury and promote
      neuronal survival during development. The authors have used enzyme-linked
      immunosorbent assay to study levels of nerve growth factor in the cerebrospinal
      fluid of children with asphyxia at birth (n = 10) and of controls (n = 23).
      Compared with reference groups the children who had had severe asphyxia had lower
      or negligible levels of cerebrospinal fluid nerve growth factor in the neonatal
      period or later. The level of cerebrospinal fluid nerve growth factor measured in
      the neonatal period was 3.76+/-4.13 pg/mL in children with asphyxia (n = 8),
      which is significantly lower than in children without asphyxia or infection (n =
      10) 9.42+/-4.09 pg/mL or in those without asphyxia but with infection (n = 13)
      17.63+/-11.48 pg/mL (P = 0.0186 and P = 0.0013, respectively). However, in some
      children with asphyxia the cerebrospinal fluid nerve growth factor levels were
      virtually normal, and most importantly these children subsequently had normal
      neurologic development. These results suggest that cerebrospinal fluid nerve
      growth factor might be used as a biochemical marker for early estimates of
      hypoxic-ischemic brain damage in asphyxiated neonates.

PMID- 10082344
TI  - Neuroradiologic findings in glutaric aciduria type II.
AB  - The authors report a 3-year-old male with glutaric aciduria type II, whose
      magnetic resonance imaging studies revealed agenesis of the cerebellar vermis and
      hypoplastic temporal lobes. Proton magnetic resonance spectroscopy in the
      parietal white matter revealed a markedly increased choline/creatine ratio,
      suggesting a demyelinating process. Gas chromatographic analysis of urinary
      organic acids should be studied in any patient with agenesis of the cerebellar
      vermis and cystic renal disease to exclude glutaric aciduria type II.

PMID- 10082345
TI  - Arteriovenous fistula: a cause of torticollis.
AB  - Torticollis is a symptom that may represent a wide spectrum of disorders ranging
      from a simple etiology to a life-threatening pathology. Pediatricians have to
      suspect central nervous system abnormalities whenever faced with torticollis. The
      authors report an arteriovenous fistula at the craniocervical junction in a
      patient presenting with torticollis.

PMID- 10082346
TI  - MRI diagnosis of gliomatosis cerebri.
AB  - Until recently the diagnosis of gliomatosis cerebri has been made on postmortem
      examination. This article reviews the use of serial magnetic resonance imaging
      studies to suggest premorbid diagnosis of this condition. The following is a case
      report of a 14-year-old female who had a subtotal cortical resection of tumor and
      several years later developed a progressive dementia. At postmortem examination
      the diagnosis of gliomatosis cerebri was made. Diffuse progressive white matter
      changes involving both hemispheres and brainstem, with increased thickness of the
      corpus callosum and without changes in cortical markings on T2-weighted magnetic
      resonance images, in this patient were highly suggestive of the diagnosis of
      gliomatosis cerebri.

PMID- 10082347
TI  - Cauda equina syndrome complicating pneumococcal meningitis.
AB  - A 14-month-old female with pneumococcal meningitis presented with flaccid
      paraplegia, saddle anesthesia, and bladder and bowel dysfunction. Magnetic
      resonance imaging of the spine demonstrated intense gadolinium enhancement of the
      cauda equina, whereas the conus medullaris appeared normal. This finding
      indicated that lumbosacral polyradiculopathy caused her symptoms.

PMID- 10082348
TI  - Spinal arachnoid cyst with weakness in the limbs and abdominal pain.
AB  - A 7-year-old male admitted with neck rigidity, severe pain in the abdomen, and
      progressive weakness in the lower limbs was diagnosed as having a spinal
      intramedullary arachnoid cyst. There was a dramatic and immediate recovery after
      fenestration of the cyst.

PMID- 10082349
TI  - Dermoid cyst with dermal sinus tract complicated with spinal subdural abscess.
AB  - Spinal subdural abscess caused by spread of infection with the dermal sinus tract
      is rare in children. This article reports on a 1-year-old male with prolonged
      fever, progressive paraplegia, and bowel and bladder dysfunction resulting from a
      spinal subdural abscess secondary to an infected spinal dermoid cyst with a
      dermal sinus tract. This is the youngest patient to be reported having this
      condition. Surgical intervention was performed to find a tumor that had capsule
      and keratinlike contents. Culture of the abscess was positive for Escherichia
      coli and Bacteroides vulgatus. He received 6 weeks of parenteral antibiotic
      treatment. This patient illustrates the importance of urgent radiologic
      examination, immediate surgical resection, and appropriate antibiotic therapy for
      spinal subdural abscess.

PMID- 10082350
TI  - Efficacy of lamotrigine in refractory neonatal seizures.
AB  - A newborn infant with seizures of unknown etiology that were refractory to
      treatment with phenobarbitone, phenytoin, midazolam, clonazepam, and vigabatrin
      is reported. The introduction of the new antiepileptic drug lamotrigine was
      followed by rapid and sustained control of the seizures.

PMID- 10082351
TI  - Volume flow measurement in hemodialysis shunts using time-domain correlation.
AB  - Volume flow was measured in 58 hemodialysis shunts (32 grafts and 26 radial
      fistulas) using the color velocity imaging-quantification method. This method is
      based on time-domain correlation for velocity calculation and integration of time
      varying velocity profiles generated by M-mode sampling. Measurements were made in
      the brachial artery to estimate radial fistula flow or directly in the grafts.
      Intraoperator reproducibility was 14.9% for fistulas and 11.6% for grafts. Flow
      rate was significantly lower in abnormal shunts associated with a functional
      disorder or a morphologic complication (808 ml/min +/- 484) than in shunts
      associated with no abnormalities (1401 ml/min +/- 562). Receiver operating
      characteristic curves showed that a flow rate of 900 ml/min for fistulas and 1300
      ml/min for grafts provided 81% and 79% sensitivity and 79% and 67% specificity,
      respectively. A functional disorder or a morphologic complication was associated
      with all fistulas and grafts in which flow rates were lower than 500 ml/min and
      800 ml/min, respectively.

PMID- 10082352
TI  - Signal-enhanced color Doppler sonography of deep venous thrombosis in the lower
      limbs and pelvis.
AB  - Detection of Doppler signal tends to be more difficult in peripheral veins owing
      to low flow velocity. This can be caused by nonoccluding thrombosis, post
      thrombotic wall changes, or a deep anatomic location of pelvic veins. The last
      mentioned frequently is accompanied by interference by bowel gas. In addition,
      inappropriate insonation angles adversely affect the outcome of color-coded
      Doppler interrogation. The purpose of the present study was to evaluate the
      effectiveness of signal-enhanced color Doppler sonography on peripheral veins in
      31 patients clinically suspected of having deep vein thrombosis. As a result of
      diagnostic uncertainty, additional enhanced studies were performed on 43 venous
      segments. The enhancement led to a decrease in false-positive results (from four
      patients to one patient) and false-negative results (from four patients to two
      patients) compared to unenhanced studies. Evaluation of the deeply located pelvic
      veins profited the most through signal enhanced Doppler sonography.

PMID- 10082353
TI  - Lumen reduction measurements of the internal carotid artery before and after
      Levovist enhancement: reproducibility and agreement with angiography.
AB  - Our aim was to assess reproducibility of three different lumen reduction
      measuring methods--North American Symptomatic Carotid Endarterectomy Trial,
      European Carotid Surgery Trial, and common carotid--using power Doppler and color
      Doppler sonography before and after Levovist enhancement. We included 20
      symptomatic patients with mild or severe carotid disease. North American
      Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial, and
      common carotid measurements on longitudinal views and European Carotid Surgery
      Trial measurements on transverse views were performed. Examinations were repeated
      and the results compared to assess reproducibility of measurements. Correlation
      with angiography was obtained by calculating Pearson correlation coefficients.
      Reproducibility was significantly better (P < 0.05) for European Carotid Surgery
      Trial and common carotid measurements (95% limits of agreement between -10% to
      10% and -19% to 17%) as compared to North American Symptomatic Carotid
      Endarterectomy Trial measurements (95% limits of agreement between -11% to 21%
      and -21% to 23%). Variability of measurements after enhancement increased
      slightly (not significant) for both power and color Doppler sonography.
      Additionally, European Carotid Surgery Trial measurements, using nonenhanced
      power Doppler or color Doppler sonography, did not correlate significantly with
      angiography, whereas North American Symptomatic Carotid Endarterectomy Trial and
      common carotid measurements correlated well with angiography, particularly in
      power Doppler mode after enhancement (r = 0.88 and r = 0.82, respectively). We
      conclude that for lumen reduction measurements of the internal carotid artery
      with power and color Doppler sonography, the common carotid method is the only
      method that is reproducible and has good correlation with angiography, which
      slightly improves after Levovist enhancement.

PMID- 10082354
TI  - Coanda effect on ductal flow in the pulmonary artery.
AB  - The Coanda effect (the tendency of a jet stream to adhere to a boundary wall),
      and the relevant anatomy, may explain the location of ductal jets within the main
      pulmonary artery. With the usual insertion of the duct close to the left
      pulmonary artery, during right ventricular ejection, the ductal jet adheres to
      the left wall of the main pulmonary artery. When right ventricular ejection is
      absent in pulmonary atresia, the ductal jet streams down the right wall of the
      pulmonary artery to the pulmonary valve, reverses, and maintains a parallel
      column back toward the bifurcation. If the reversed flow is mistaken for ejection
      from the right ventricle, the diagnosis of pulmonary atresia may be missed.

PMID- 10082355
TI  - Use of ultrasonography in the patient with acute renal trauma.
AB  - The purpose of this study was to assess the use of emergent ultrasonographic
      examination in acute traumatic renal injuries. Over a 3 year period, prospective
      data of all patients who had an emergency ultrasonogram were recorded. Thirty-two
      patients with 37 renal injuries were studied retrospectively to identify in how
      many patients the sonogram detected free fluid or a renal parenchymal
      abnormality. Free fluid in the abdomen was identified in 19 of 32 patients (59%).
      However, 12 of these 19 patients had concomitant injury, such as splenic rupture
      requiring splenectomy, severe liver lacerations, or bowel lacerations requiring
      repair, that were possible causes of the free fluid. Eliminating these patients,
      only seven of 20 patients with isolated renal injuries had free fluid in the
      abdomen (35%), whereas 13 of 20 patients (65%) had no evidence of free fluid. All
      seven patients with free fluid had moderate or severe renal injuries. Renal
      parenchymal abnormalities were identified on ultrasonograms in eight of 37 (22%)
      of injured kidneys. The abnormalities were detected more commonly in cases of
      severe injury (60%). In conclusion, acute injuries of the kidney from blunt
      abdominal trauma often are associated with significant splenic, hepatic, or bowel
      trauma. Isolated renal injuries frequently occur without the presence of free
      fluid in the abdomen. Furthermore, the ultrasonogram of the kidney often is
      normal with acute renal injuries, but it is more likely to be abnormal with
      severe (grade II or greater) renal injuries. Sonography may be used in the triage
      of patients with blunt abdominal trauma and possible renal injury. However, a
      negative ultrasonogram does not exclude renal injury, and, depending on clinical
      and laboratory findings, other imaging procedures such as computed tomography
      should be performed.

PMID- 10082356
TI  - Benign papillary lesions of the breast: sonographic-pathologic correlation.
AB  - We reviewed the sonographic findings of 42 benign papillary lesions of the breast
      and correlated them with pathologic findings. Sonography detected 95% of
      papillomas (22 intraluminal masses, four extraductal masses, nine purely solid
      masses, and five mixed type masses). The sonographic margins of the mass were
      well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined
      margins on sonography were frequent in papillomas with pathologic pseudoinvasion
      and in juvenile papillomatosis. Most benign papillary lesions of the breast have
      the sonographic findings suggestive of intraductal origin. The sonographic
      findings of papillary lesions correlated well with pathologic findings.

PMID- 10082357
TI  - Use of ultrasonography in the diagnosis of osteomalacia: preliminary results on
      experimental osteomalacia in the rat.
AB  - This study was performed to investigate the ability of ultrasonographic technique
      to distinguish osteomalacia from normal bone with the same mineral content. Ten
      rats with experimentally induced osteomalacia (group A) and 12 control rats
      having similar body size and weight (group B) were studied. Histomorphometric
      analysis confirmed the presence of osteomalacia in two rats from group A and
      showed normally mineralized bone in two rats from group B. Whole body bone
      mineral density, measured by dual-energy x-ray absorptiometry, was similar in the
      two groups (86 +/- 6 mg/cm2 in group A and 89 +/- 4 mg/cm2 in group B). The
      velocity of the ultrasound beam in bone was measured by densitometer at the first
      caudal vertebra of each rat. The velocity was measured when the first peak of the
      waveform reached a predetermined minimum amplitude value (amplitude-dependent
      speed of sound) as well as at the lowest point of this curve before it reaches
      the predetermined minimum amplitude (first minimum speed of sound). Although the
      amplitude-dependent speed of sound was similar in the two groups (1381.9 +/- 11.8
      m/s in group A and 1390.9 +/- 17.8 m/s in group B), the first minimum speed of
      sound was clearly different (1446.1 +/- 8.9 m/s in group A and 1503.3 +/- 10.9
      m/s in group B; P < 0.001). This study shows that ultrasonography could be used
      to identify alterations in bone quality, such as osteomalacia, but further
      studies need to be carried out before this method can be introduced into clinical
      practice.

PMID- 10082358
TI  - Normal splenic volumes estimated using three-dimensional ultrasonography.
AB  - The purposes of this study were to determine splenic volumes using three
      dimensional ultrasonography and to compare these measurements with two
      dimensional splenic indices. Fifty-two healthy volunteers were studied. Two
      dimensional volume measurements were based on length, width, and thickness, and
      the splenic index was calculated using the standard prolated ellipsoid formula
      (length x width x thickness x 0.523). Three-dimensional volume planar
      measurements were obtained with a slice by slice technique by manually drawing a
      region of interest around the spleen from one end of the sweep to the opposite
      end. These measurements were recorded three times by two observers. In addition,
      in vitro determination of splenic volume was performed using three cadaveric
      human spleens in a water bath. No statistically significant interobserver or
      intraobserver variability was present for either two-dimensional or three
      dimensional ultrasonography. Three-dimensional sonographic estimations of planar
      splenic volumes and ellipsoid splenic volumes were consistently smaller than two
      dimensional sonographic estimations of splenic volumes. Three-dimensional
      sonographic splenic volumes calculated in vitro using the planar method were
      accurate to within 2% of in vitro water displacement volumes. Three-dimensional
      ultrasonography is potentially superior to two-dimensional sonography for
      evaluation of irregularly shaped objects, such as the spleen, and can provide
      improved accuracy over that of traditional two-dimensional techniques.

PMID- 10082359
TI  - Transvaginal ultrasonography in the assessment of organic diseases of female
      urethra.
AB  - The current investigation aimed to check the effectiveness of transvaginal
      ultrasonography in the diagnosis of organic urethral diseases, comparing its
      results with those of conventional examinations (physical examination, voiding
      cystourethrography, pelvic ultrasonography, cystourethroscopy). Transvaginal
      ultrasonography was performed in 560 female patients with recurrent cystitis,
      dysuria, or palpable masses and diagnosed the following urethral diseases: 25
      diverticula, seven stenoses, three carcinomas, two leiomyomas of periurethral
      tissue, and one incomplete duplex urethra. In our study transvaginal
      ultrasonography proved to be the most reliable diagnostic tool among imaging
      methods used.

PMID- 10082360
TI  - Ultrasonographic diagnosis of postpartum aborting large intracavitary leiomyoma.

PMID- 10082361
TI  - Prenatal diagnosis of myelocystoceles: report of two cases.

PMID- 10082362
TI  - Improved definition of left atrial thrombus by tissue harmonic imaging.

PMID- 10082363
TI  - All in the family: structural and evolutionary relationships among three modular
      proteins with diverse functions and variable assembly.
AB  - The crystal structures of three proteins of diverse function and low sequence
      similarity were analyzed to evaluate structural and evolutionary relationships.
      The proteins include a bacterial bleomycin resistance protein, a bacterial
      extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as
      phylogenetic analyses, strongly indicate that the modern family of proteins
      represented by these structures arose through a rich evolutionary history that
      includes multiple gene duplication and fusion events. These events appear to be
      historically shared in some cases, but parallel and historically independent in
      others. A significant early event is proposed to be the establishment of metal
      binding in an oligomeric ancestor prior to the first gene fusion. Variations in
      the spatial arrangements of homologous modules are observed that are consistent
      with the structural principles of three-dimensional domain swapping, but in the
      unusual context of the formation of larger monomers from smaller dimers or
      tetramers. The comparisons support a general mechanism for metalloprotein
      evolution that exploits the symmetry of a homooligomeric protein to originate a
      metal binding site and relies upon the relaxation of symmetry, as enabled by gene
      duplication, to establish and refine specific functions.

PMID- 10082364
TI  - Improving the binding affinity of an antibody using molecular modeling and site
      directed mutagenesis.
AB  - Activated Factor X releases F1.2, a 271-amino acid peptide, from the amino
      terminus of prothrombin during blood coagulation. A nine-amino acid peptide, C9
      (DSDRAIEGR), corresponding to the carboxyl terminus of F1.2 was synthesized and
      used to produce a monoclonal antibody, TA1 (K(D)) 1.22 x 10(-6) M). To model the
      TA1 antibody, we entered the sequence information of the cloned TA1 Fv into the
      antibody modeling program, ABM, which combines homology methods, conformational
      search procedures, and energy screening and has proved to be a reliable and
      reproducible antibody modeling method. Using a novel protein fusion procedure, we
      expressed the C9 peptide fused to the carboxyl terminus of the PENI repressor
      protein from Bacillus licheniformis in Escherichia coli. We constructed fusion
      proteins containing alanine substitutions for each amino acid in the C9 epitope.
      Binding studies, using the C9 alanine mutants and TA1, and spatial constraints
      predicted by the modeled TA1 binding cleft enabled us to establish a plausible
      conformation for C9 complexed with TA1. Furthermore, based on binding results of
      conservative amino acid substitutions in C9 and mutations in the antibody, we
      were able to refine the complex model and identify antibody mutations that would
      improve binding affinity.

PMID- 10082365
TI  - Correlation between the 1.6 A crystal structure and mutational analysis of
      keratinocyte growth factor.
AB  - A comprehensive deletion, mutational, and structural analysis of the native
      recombinant keratinocyte growth factor (KGF) polypeptide has resulted in the
      identification of the amino acids responsible for its biological activity. One of
      these KGF mutants (delta23KGF-R144Q) has biological activity comparable to the
      native protein, and its crystal structure was determined by the multiple
      isomorphous replacement plus anomalous scattering method (MIRAS). The structure
      of KGF reveals that it folds into a beta-trefoil motif similar to other members
      of fibroblast growth factor (FGF) family whose structures have been resolved.
      This fold consists of 12 anti-parallel beta-strands in which three pairs of the
      strands form a six-stranded beta-barrel structure and the other three pairs of
      beta-strands cap the barrel with hairpin triplets forming a triangular array. KGF
      has 10 well-defined beta strands, which form five double-stranded anti-parallel
      beta-sheets. A sixth poorly defined beta-strand pair is in the loop between
      residues 133 and 144, and is defined by only a single hydrogen bond between the
      two strands. The KGF mutant has 10 additional ordered amino terminus residues (24
      33) compared to the other FGF structures, which are important for biological
      activity. Based on mutagenesis, thermal stability, and structural data we
      postulate that residues TRP125, THR126, and His127 predominantly confer receptor
      binding specificity to KGF. Additionally, residues GLN152, GLN138, and THR42 are
      implicated in heparin binding. The increased thermal stability of delta23KGF
      R144Q can structurally be explained by the additional formation of hydrogen bonds
      between the GLN side chain and a main-chain carbonyl on an adjoining loop. The
      correlation of the structure and biochemistry of KGF provides a framework for a
      rational design of this potentially important human therapeutic.

PMID- 10082366
TI  - Binding of a substrate analog to a domain swapping protein: X-ray structure of
      the complex of bovine seminal ribonuclease with uridylyl(2',5')adenosine.
AB  - Bovine seminal ribonuclease (BS-RNase) is a unique member of the pancreatic-like
      ribonuclease superfamily. The native enzyme is a mixture of two dimeric forms
      with distinct structural features. The most abundant form is characterized by the
      swapping of N-terminal fragments. In this paper, the crystal structure of the
      complex between the swapping dimer and uridylyl(2',5')adenosine is reported at
      2.06 A resolution. The refined model has a crystallographic R-factor of 0.184 and
      good stereochemistry. The quality of the electron density maps enables the
      structure of both the inhibitor and active site residues to be unambiguously
      determined. The overall architecture of the active site is similar to that of
      RNase A. The dinucleotide adopts an extended conformation with the pyrimidine and
      purine base interacting with Thr45 and Asn71, respectively. Several residues
      (Gln11, His12, Lys41, His119, and Phe120) bind the oxygens of the phosphate
      group. The structural similarity of the active sites of BS-RNase and RNase A
      includes some specific water molecules believed to be relevant to catalytic
      activity. Upon binding of the dinucleotide, small but significant modifications
      of the tertiary and quaternary structure of the protein are observed. The ensuing
      correlation of these modifications with the catalytic activity of the enzyme is
      discussed.

PMID- 10082367
TI  - Analysis of zinc binding sites in protein crystal structures.
AB  - The geometrical properties of zinc binding sites in a dataset of high quality
      protein crystal structures deposited in the Protein Data Bank have been examined
      to identify important differences between zinc sites that are directly involved
      in catalysis and those that play a structural role. Coordination angles in the
      zinc primary coordination sphere are compared with ideal values for each
      coordination geometry, and zinc coordination distances are compared with those in
      small zinc complexes from the Cambridge Structural Database as a guide of
      expected trends. We find that distances and angles in the primary coordination
      sphere are in general close to the expected (or ideal) values. Deviations occur
      primarily for oxygen coordinating atoms and are found to be mainly due to H
      bonding of the oxygen coordinating ligand to protein residues, bidentate binding
      arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing
      residues (or water) to zinc bound histidines is almost universal in our dataset
      and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that
      carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn
      motifs show the most geometrical variation. As catalytic motifs have a higher
      proportion of carboxyl elec atoms than structural motifs, they provide a more
      rigid framework for zinc binding. This is understood biologically, as a small
      distortion in the zinc position in an enzyme can have serious consequences on the
      enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and
      residues that provide elecs, and identify conserved hydrophobic residues in the
      endopeptidases that also appear to contribute to stabilizing the catalytic zinc
      site. A zinc binding template in protein crystal structures is derived from these
      observations.

PMID- 10082368
TI  - Thermodynamics of the reconstitution of tuna cytochrome c from two peptide
      fragments.
AB  - Two peptide fragments from tuna cytochrome c (cyt c), N-fragment (residues 1-44
      containing the heme) and C-fragment (residues 45-103), combine to form a 1:1
      fragment complex. This was clearly proved by ion-spray mass spectrometry. It was
      found from CD and NMR spectra that the structure of the fragment complex formed
      is similar to that of an intact cyt c, although each isolated fragment itself is
      unstructured. Binding constants and enthalpies upon the complex formation were
      directly observed by isothermal titration calorimetry. Thermodynamic parameters
      (deltaG(o)b, deltaHb, deltaS(o)b, and deltaC(b)p)) associated with the complex
      formation were determined at various pHs and temperatures. DeltaHb was found to
      be almost independent of pH values. The change in heat capacity accompanying the
      complex formation (deltaC(b)p) was directly determined from the temperature
      dependence of deltaHb. In addition, the change in heat capacity and enthalpy upon
      tuna cyt c unfolding were determined by differential scanning calorimetry.
      Thermodynamic parameters for the unfolding/dissociation process of the fragment
      complex were compared with those for cyt c unfolding at pH 3.9 and 303 K. In a
      comparison of two unfolding processes, the heat capacity change of each was very
      close to the other, while both the unfolding enthalpy and entropy of the fragment
      complex were larger than those of tuna cyt c. These thermodynamic data suggest
      that the internal interactions between polar groups (hydrogen bonding) and
      nonpolar groups (van der Waals interactions) are preserved in the fragment
      complex as well as in the native state of cyt c.

PMID- 10082369
TI  - Role of P225 and the C136-C201 disulfide bond in tissue plasminogen activator.
AB  - The protease domain of tissue plasminogen activator (tPA), a key fibrinolytic
      enzyme, was expressed in Escherichia coli with a yield of 1 mg per liter of
      media. The recombinant protein was titrated with the Erythrina caraffa trypsin
      inhibitor (ETI) and characterized in its interaction with plasminogen and the
      natural inhibitor plasminogen activator inhibitor-1 (PAI-1). Analysis of the
      catalytic properties of tPA using a library of chromogenic substrates carrying
      substitutions at P1, P2, and P3 reveals a strong preference for Arg over Lys at
      P1, unmatched by other serine proteases like thrombin or trypsin. In contrast to
      these proteases and plasmin, tPA shows little or no preference for Pro over Gly
      at P2. A specific inhibition of tPA by Cu2+ was discovered. The divalent cation
      presumably binds to H188 near D189 in the primary specificity pocket and inhibits
      substrate binding in a competitive manner with a Kd = 19 microM. In an attempt to
      engineer Na+ binding and enhanced catalytic activity in tPA, P225 was replaced
      with Tyr, the residue present in Na+-dependent allosteric serine proteases. The
      P225Y mutation did not result in cation binding, but caused a significant loss of
      specificity (up to 100-fold) toward chromogenic substrates and plasminogen and
      considerably reduced the inhibition by PAI-1 and ETI. Interestingly, the P225Y
      substitution enhanced the ability of Cu2+ to inhibit the enzyme. Elimination of
      the C136-C201 disulfide bond, that is absent in all Na+-dependent allosteric
      serine proteases, significantly enhanced the yield (5 mg per liter of media) of
      expression in E. coli, but caused no changes in the properties of the enzyme
      whether residue 225 was Pro or Tyr. These findings point out an unanticipated
      crucial role for residue 225 in controlling the catalytic activity of tPA, and
      suggest that engineering of a Na+-dependent allosteric enhancement of catalytic
      activity in this enzyme, must involve substantial changes in the region
      homologous to the Na+ binding site of allosteric serine proteases.

PMID- 10082370
TI  - Role of the 6-20 disulfide bridge in the structure and activity of epidermal
      growth factor.
AB  - Two synthetic analogues of murine epidermal growth factor, [Abu6, 20] mEGF4-48
      (where Abu denotes amino-butyric acid) and [G1, M3, K21, H40] mEGF1-48, have been
      investigated by NMR spectroscopy. [Abu6, 20] mEGF4-48 was designed to determine
      the contribution of the 6-20 disulfide bridge to the structure and function of
      mEGF. The overall structure of this analogue was similar to that of native mEGF,
      indicating that the loss of the 6-20 disulfide bridge did not affect the global
      fold of the molecule. Significant structural differences were observed near the N
      terminus, however, with the direction of the polypeptide chain between residues
      four and nine being altered such that these residues were now located on the
      opposite face of the main beta-sheet from their position in native mEGF. Thermal
      denaturation experiments also showed that the structure of [Abu6, 20] mEGF4-48
      was less stable than that of mEGF. Removal of this disulfide bridge resulted in a
      significant loss of both mitogenic activity in Balb/c 3T3 cells and receptor
      binding on A431 cells compared with native mEGF and mEGF4-48, implying that the
      structural changes in [Abu6, 20] mEGF4-48, although limited to the N-terminus,
      were sufficient to interfere with receptor binding. The loss of binding affinity
      probably arose mainly from steric interactions of the dislocated N-terminal
      region with part of the receptor binding surface of EGF. [G1, M3, K21, H40] mEGF1
      48 was also synthesized in order to compare the synthetic polypeptide with the
      corresponding product of recombinant expression. Its mitogenic activity in Balb/c
      3T3 cells was similar to that of native mEGF and analysis of its 1H chemical
      shifts suggested that its structure was also very similar to native.

PMID- 10082371
TI  - Molecular mechanisms of resistance: free energy calculations of mutation effects
      on inhibitor binding to HIV-1 protease.
AB  - The changes in the inhibitor binding constants due to the mutation of isoleucine
      to valine at position 84 of HIV-1 protease are calculated using molecular
      dynamics simulations. The calculations are done for three potent inhibitors--KNI
      272, L-735,524 (indinavir or MK-639), and Ro 31-8959 (saquinavir). The
      calculations agree with the experimental data both in terms of an overall trend
      and in the magnitude of the resulting free energy change. HIV-1 protease is a
      homodimer, so each mutation causes two changes in the enzyme. The decrease in the
      binding free energy from each mutated side chain differs among the three
      inhibitors and correlates well with the size of the cavities induced in the
      protein interior near the mutated residue. The cavities are created as a result
      of a mutation to a smaller side chain, but the cavities are less than would be
      predicted from the wild-type structures, indicating that there is significant
      relaxation to partially fill the cavities.

PMID- 10082372
TI  - Probing enzyme quaternary structure by combinatorial mutagenesis and selection.
AB  - Genetic selection provides an effective way to obtain active catalysts from a
      diverse population of protein variants. We have used this tool to investigate the
      role of loop sequences in determining the quaternary structure of a domain
      swapped enzyme. By inserting random loops of four to seven residues into a
      dimeric chorismate mutase and selecting for functional variants by genetic
      complementation, we have obtained and characterized both monomeric and hexameric
      enzymes that retain considerable catalytic activity. The low percentage of active
      proteins recovered from these selection experiments indicates that relatively few
      loop sequences permit a change in quaternary structure without affecting active
      site structure. The results of our experiments suggest further that protein
      stability can be an important driving force in the evolution of oligomeric
      proteins.

PMID- 10082373
TI  - Enzyme-mononucleotide interactions: three different folds share common structural
      elements for ATP recognition.
AB  - Three ATP-dependent enzymes with different folds, cAMP-dependent protein kinase,
      D-Ala:D-Ala ligase and the alpha-subunit of the alpha2beta2 ribonucleotide
      reductase, have a similar organization of their ATP-binding sites. The most
      meaningful similarity was found over 23 structurally equivalent residues in each
      protein and includes three strands each from their beta-sheets, in addition to a
      connecting loop. The equivalent secondary structure elements in each of these
      enzymes donate four amino acids forming key hydrogen bonds responsible for the
      common orientation of the "AMP" moieties of their ATP-ligands. One lysine residue
      conserved throughout the three families binds the alpha-phosphate in each
      protein. The common fragments of structure also position some, but not all, of
      the equivalent residues involved in hydrophobic contacts with the adenine ring.
      These examples of convergent evolution reinforce the view that different proteins
      can fold in different ways to produce similar structures locally, and nature can
      take advantage of these features when structure and function demand it, as shown
      here for the common mode of ATP-binding by three unrelated proteins.

PMID- 10082374
TI  - Selecting near-native conformations in homology modeling: the role of molecular
      mechanics and solvation terms.
AB  - A free energy function, combining molecular mechanics energy with empirical
      solvation and entropic terms, is used for ranking near-native conformations that
      occur in the conformational search steps of homology modeling, i.e., side-chain
      search and loop closure calculations. Correlations between the free energy and
      RMS deviation from the X-ray structure are established. It is shown that
      generally both molecular mechanics and solvation/entropic terms should be
      included in the potential. The identification of near-native backbone
      conformations is accomplished primarily by the molecular mechanics term that
      becomes the dominant contribution to the free energy if the backbone is even
      slightly strained, as frequently occurs in loop closure calculations. Both terms
      become equally important if a sufficiently accurate backbone conformation is
      found. Finally, the selection of the best side-chain positions for a fixed
      backbone is almost completely governed by the solvation term. The discriminatory
      power of the combined potential is demonstrated by evaluating the free energies
      of protein models submitted to the first meeting on Critical Assessment of
      techniques for protein Structure Prediction (CASP1), and comparing them to the
      free energies of the native conformations.

PMID- 10082375
TI  - The role of the 6 lysines and the terminal amine of Escherichia coli single
      strand binding protein in its binding of single-stranded DNA.
AB  - Differential chemical modification of the lysines and amino-terminus of
      Escherichia coli single-strand binding (SSB) protein was used to determine their
      roles in the binding of SSB to single-stranded DNA (ssDNA). A combination of
      isotope labeling and mass spectrometry was used to determine the rates at which
      SSB was acetylated by acetic anhydride. First, SSB was labeled by deuterated
      acetic anhydride for given lengths of time in the presence or absence of single
      stranded ssDNA. Then, the protein was denatured and completely acetylated by
      nondeuterated acetic anhydride. Enzymatic digests of the completely acetylated,
      isotopically labeled SSB were analyzed by electrospray ionization mass
      spectrometry. The intensities of the deuterated and nondeuterated forms of
      acetylated peptides provided accurate quantification of the reactivity of the
      amines in native SSB, either free or bound to ssDNA. Acetylation rate constants
      were determined from time course measurements. In the absence of ssDNA, the
      terminal alpha-amine of SSB was 10-fold more reactive than Lys residues at
      positions 43, 62, 73, and 87. The reactivities of Lys 7 and 49 were much lower
      yet, suggesting that they have very limited access to solution under any
      condition. In the presence of ssDNA, the reactivities of the amino-terminus and
      Lys residues 43, 62, 73, and 87 were reduced by factors of 3.7-25, indicating
      that the environments around all of these amines is substantially altered by
      binding of SSB to ssDNA. Three of these residues are located near putative ssDNA
      binding sites, whereas Lys 87 is located at the monomer-monomer interface.

PMID- 10082376
TI  - The magnitude of changes in guanidine-HCl unfolding m-values in the protein, iso
      1-cytochrome c, depends upon the substructure containing the mutation.
AB  - Hydrophilic to hydrophobic mutations have been made at 11 solvent exposed sites
      on the surface of iso-1-cytochrome c. Most of these mutations involve the
      replacement of lysine with methionine, which is nearly isosteric with lysine.
      Minimal perturbation to the native structure is expected, and this expectation is
      confirmed by infrared amide I spectroscopy. Guanidine hydrochloride denaturation
      studies demonstrate that these variants affect the magnitude of the m-value, the
      rate of change of free energy with respect to denaturant concentration, to
      different degrees. Changes in m-values are indicative of changes in the
      equilibrium folding mechanism of a protein. Decreases in m-values are normally
      thought to result either from an increased population of intermediates during
      unfolding or from a more compact denatured state. When cytochrome c is considered
      in terms of its thermodynamic substructures, the changes in the m-value for a
      given variant appear to depend upon the substructure in which the mutation is
      made. These data indicate that the relative stabilities and physical properties
      of substructures of cytochrome c play an important determining role in the
      equilibrium folding mechanism of this protein.

PMID- 10082377
TI  - Efficient sequence analysis of the six gene products (7-74 kDa) from the
      Escherichia coli thiamin biosynthetic operon by tandem high-resolution mass
      spectrometry.
AB  - The 10(5) resolving power and MS/MS capabilities of Fourier-transform mass
      spectrometry provide electrospray ionization mass spectra containing >100
      molecular and fragment ion mass values of high accuracy. Applying these spectra
      to the detection and localization of errors and modifications in the DNA-derived
      sequences of proteins is illustrated with the thiCEFSGH thiamin biosynthesis
      operon from Escherichia coli. Direct fragmentation of the multiply-charged intact
      protein ions produces large fragment ions covering the entire sequence; further
      dissociation of these fragment ions provides information on their sequences. For
      ThiE (23 kDa), the entire sequence was verified in a single spectrum with an
      accurate (0.3 Da) molecular weight (Mr) value, with confirmation from MS/MS
      fragment masses. Those for ThiH (46 kDa) showed that the Mr value (1 Da error)
      represented the protein without the start Met residue. For ThiF (27 kDa), MS/MS
      localized a sequence discrepancy to a 34 residue peptide. The first 107 residues
      of ThiC (74 kDa) were shown to be correct, with C-terminal heterogeneity
      indicated. For ThiG (predicted Mr = 34 kDa), ESI/FTMS showed two components of
      7,310.74 (ThiS) and 26,896.5 Da (ThiG); MS/MS uncovered three reading frame
      errors and a stop codon for the first protein. MS/MS ions are consistent with 68
      fragments predicted by the corrected ThiS/ThiG DNA sequences.

PMID- 10082378
TI  - Aromatic L-amino acid decarboxylase: conformational change in the flexible region
      around Arg334 is required during the transaldimination process.
AB  - Aromatic L-amino acid decarboxylase (AADC) catalytic mechanism has been proposed
      to proceed through two consecutive intermediates (i.e., Michaelis complex and the
      external aldimine). Limited proteolysis of AADC that preferentially digested at
      the C-terminal side of Arg334 was slightly retarded in the presence of
      dihydroxyphenyl acetate that formed a stable Michaelis complex. On the contrary,
      AADC was scarcely digested in the presence of L-dopa methyl ester that formed a
      stable external aldimine. Similar protection by the substrate analogs was
      observed in the chemical modification experiment. From these results, we
      concluded that the region around Arg334 must be exposed and flexible in the
      unliganded state, and forming the Michaelis complex generated a subtle
      conformational change, then underwent marked conformational change during the
      subsequent transaldimination process prerequisite to forming the external
      aldimine. For further analyses, we constructed a mutant gene encoding in tandem
      the two peptides of AADC cleaved at the Asn327-Met328 bond inside the putative
      flexible region. The gene product, fragmentary AADC, was still active with L-dopa
      as substrate, but its k(cat) value was decreased 57-fold, and the Km value was
      increased 9-fold compared with those of the wild-type AADC. The absorption
      spectra of the fragmentary AADC in the presence of L-dopa methyl ester showed
      shift in the equilibrium of the transaldimination from the external aldimine to
      the Michaelis complex. Tryptic digestion of the fragmentary AADC removed seven
      amino acid residues, Met328-Arg334, and resulted in complete inactivation.
      Susceptibility of the fragmentary enzyme to trypsin was not changed by L-dopa
      methyl ester revealing the loss of appropriate conformational change in the
      flexible region induced by substrate binding. From these results we propose that
      the conformational change in the flexible region is required during the
      transaldimination process.

PMID- 10082379
TI  - Opposite behavior of two isozymes when refolding in the presence of non-ionic
      detergents.
AB  - GroEL has a greater affinity for the mitochondrial isozyme (mAAT) of aspartate
      aminotransferase than for its cytosolic counterpart (cAAT) (Mattingly JR Jr,
      Iriarte A, Martinez-Carrion M, 1995, J Biol Chem 270:1138-1148), two proteins
      that share a high degree of sequence similarity and an almost identical spatial
      structure. The effect of detergents on the refolding of these large, dimeric
      isozymes parallels this difference in behavior. The presence of non-ionic
      detergents such as Triton X-100 or lubrol at concentrations above their critical
      micelle concentration (CMC) interferes with reactivation of mAAT unfolded in
      guanidinium chloride but increases the yield of cAAT refolding at low
      temperatures. The inhibitory effect of detergents on the reactivation of mAAT
      decreases progressively as the addition of detergents is delayed after starting
      the refolding reaction. The rate of disappearance of the species with affinity
      for binding detergents coincides with the slowest of the two rate-limiting steps
      detected in the refolding pathway of mAAT. Limited proteolysis studies indicate
      that the overall structure of the detergent-bound mAAT resembles that of the
      protein in a complex with GroEL. The mAAT folding intermediates trapped in the
      presence of detergents can resume reactivation either upon dilution of the
      detergent below its CMC or by adding beta-cyclodextrin. Thus, isolation of
      otherwise transient productive folding intermediates for further characterization
      is possible through the use of detergents.

PMID- 10082380
TI  - Turn scanning by site-directed mutagenesis: application to the protein folding
      problem using the intestinal fatty acid binding protein.
AB  - We have systematically mutated residues located in turns between beta-strands of
      the intestinal fatty acid binding protein (IFABP), and a glycine in a half turn,
      to valine and have examined the stability, refolding rate constants and ligand
      dissociation constants for each mutant protein. IFABP is an almost all beta-sheet
      protein exhibiting a topology comprised of two five-stranded sheets surrounding a
      large cavity into which the fatty acid ligand binds. A glycine residue is located
      in seven of the eight turns between the antiparallel beta-strands and another in
      a half turn of a strand connecting the front and back sheets. Mutations in any of
      the three turns connecting the last four C-terminal strands slow the folding and
      decrease stability with the mutation between the last two strands slowing folding
      dramatically. These data suggest that interactions between the last four C
      terminal strands are highly cooperative, perhaps triggered by an initial
      hydrophobic collapse. We suggest that this trigger is collapse of the highly
      hydrophobic cluster of amino acids in the D and E strands, a region previously
      shown to also affect the last stage of the folding process (Kim et al., 1997).
      Changing the glycine in the strand between the front and back sheets also results
      in a unstable, slow folding protein perhaps disrupting the D-E strand
      interactions. For most of the other turn mutations there was no apparent
      correlation between stability and refolding rate constants. In some turns, the
      interaction between strands, rather than the turn type, appears to be critical
      for folding while in others, turn formation itself appears to be a rate limiting
      step. Although there is no simple correlation between turn formation and folding
      kinetics, we propose that turn scanning by mutagenesis will be a useful tool for
      issues related to protein folding.

PMID- 10082381
TI  - A superfamily of metalloenzymes unifies phosphopentomutase and cofactor
      independent phosphoglycerate mutase with alkaline phosphatases and sulfatases.
AB  - Sequence analysis of the probable archaeal phosphoglycerate mutase resulted in
      the identification of a superfamily of metalloenzymes with similar metal-binding
      sites and predicted conserved structural fold. This superfamily unites alkaline
      phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebroside sulfatase,
      enzymes with known three-dimensional structures, with phosphopentomutase, 2,3
      bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol
      transferase, phosphonate monoesterase, streptomycin-6-phosphate phosphatase,
      alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1, and several closely
      related sulfatases. In addition to the metal-binding motifs, all these enzymes
      contain a set of conserved amino acid residues that are likely to be required for
      the enzymatic activity. Mutational changes in the vicinity of these residues in
      several sulfatases cause mucopolysaccharidosis (Hunter, Maroteaux-Lamy, Morquio,
      and Sanfilippo syndromes) and metachromatic leucodystrophy.

PMID- 10082382
TI  - Crystallization of recombinant human heme oxygenase-1.
AB  - Heme oxygenase catalyzes the NADPH, O2, and cytochrome P450 reductase dependent
      oxidation of heme to biliverdin and carbon monoxide. One of two primary isozymes,
      HO-1, is anchored to the endoplasmic reticulum membrane via a stretch of
      hydrophobic residues at the C-terminus. While full-length human HO-1 consists of
      288 residues, a truncated version with residues 1-265 has been expressed as a
      soluble active enzyme in Escherichia coli. The recombinant enzyme crystallized
      from ammonium sulfate solutions but the crystals were not of sufficient quality
      for diffraction studies. SDS gel analysis indicated that the protein had
      undergone proteolytic degradation. An increase in the use of protease inhibitors
      during purification eliminated proteolysis, but the intact protein did not
      crystallize. N-terminal sequencing and mass spectral analysis of dissolved
      crystals indicated that the protein had degraded to two major species consisting
      of residues 1-226 and 1-237. Expression of the 1-226 and 1-233 versions of human
      HO-1 provided active enzyme that crystallizes in a form suitable for diffraction
      studies. These crystals belong to space group P2(1), with unit cell dimensions a
      = 79.3 A, b = 56.3 A, c = 112.8 A, and beta = 101.5 degrees.

PMID- 10082383
TI  - Overexpression of recombinant proteins with a C-terminal thiocarboxylate:
      implications for protein semisynthesis and thiamin biosynthesis.
AB  - A facile and rapid method for the production of protein C-terminal
      thiocarboxylates on DNA-encoded polypeptides is described. This method, which
      relies on the mechanism of the cleavage reaction of intein-containing fusion
      proteins, can produce multi-milligram quantities of protein C-terminal
      thiocarboxylate quickly and inexpensively. The utility of this method for protein
      semisynthesis and implications for studies on the biosynthesis of thiamin are
      discussed.

PMID- 10082384
TI  - Identification of a Frizzled-like cysteine rich domain in the extracellular
      region of developmental receptor tyrosine kinases.
AB  - In Drosophila, members of the Frizzled family of tissue-polarity genes encode
      proteins that appear to function as cell-surface receptors for Wnts. The Frizzled
      genes belong to the seven transmembrane class of receptors (7TMR) and have on
      their extracellular region a cysteine-rich domain that has been implicated as the
      Wnt binding domain. This region has a characteristic spacing of ten cysteines,
      which has also been identified in FrzB (a secreted antagonist of Wnt signaling)
      and Smoothened (another 7TMR, which is involved in the hedgehog signalling
      pathway). We have identified, using BLAST, sequence similarity between the
      cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which
      have roles in development. These include the muscle-specific receptor tyrosine
      kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. At
      present, the ligands for these developmental tyrosine kinases are unknown. Our
      results suggest that Wnt-like ligands may bind to these developmental tyrosine
      kinases

PMID- 10082385
TI  - A genotypic characterization of enteroviral antigenic variants isolated in
      eastern Canada.
AB  - Antigenic variation within serotypes of enteroviruses can have a significant
      impact on the effectiveness of routine diagnosis by neutralization assays. The
      focus of this particular study was to initiate a genetic characterization of
      echovirus type 9 (E9) antigenic variants and nontypeable strains isolated in
      Canada from 1991 to 1993. All variant strains were initially identified by the
      serological parameter of neutralization 'breakthrough' during conventional
      serotyping using the Lim-Benyesh-Melnick antiserum pools and by assessing
      neutralization endpoints using micro-neutralization methodology. Both E9 variant
      and non-variant isolates were further characterized by sequencing amplicons
      generated from the VP2 capsid protein-coding region of these particular strains.
      Variants from the provinces of Ontario and New Brunswick were shown to include a
      number of genotypically distinct strains and all the variant strains were
      significantly different from non-variant E9 isolates when nucleotide sequences
      were compared. A similar genetic analysis of two completely non-typeable isolates
      from Quebec showed that these viruses seemed to belong to a genetic cluster of
      enteroviruses that included coxsackievirus A16 and enterovirus 71 serotypes. The
      use of genetic typing by sequence analysis provides a molecular tool for
      determining the genotypic diversity of variant and non-typeable isolates and
      their possible relatedness to other enteroviral strains.

PMID- 10082386
TI  - Identification of two lineages (WA-like and F45-like) within the major rotavirus
      genotype P[8].
AB  - The fourth gene of a porcine (S8) and eight human rotavirus isolates possessing
      the major human VP4 specificity (P1A serotype and/or P[8] genotype) were
      partially sequenced and compared to other available P[8] sequences from
      rotaviruses types G1, G3, G5 and G9 specificities which had been originally
      recovered from children with diarrhea in Japan, Brazil and the USA. Brazilian
      rotavirus S8 represented the single known porcine rotavirus with this P
      specificity. Phylogenetic analysis revealed two lineages or subgenotypes within
      P[8] strains: the F45-like P subgenotype comprised most of the strains, including
      all the human G5 isolates analyzed, whereas the Wa- or S8-like subgenotype
      consisted of only a human isolate obtained in the same geographic region as S8
      and an American strain with atypical RNA profile besides the prototypes Wa and S8
      viruses. A conserved basic amino acid residue at position 131 in VP4 seemed
      characteristic of the F45-like P[8] subgenotype.

PMID- 10082387
TI  - The defective interfering particles of equine herpesvirus 1 encode an ICP22/ICP27
      hybrid protein that alters viral gene regulation.
AB  - The genomes of equine herpesvirus 1 (EHV-1) defective interfering (DI) particles
      that mediate persistent infection were shown to encode a unique hybrid open
      reading frame composed of sequences that encode the 196 N-terminal amino acids of
      ICP22 linked in-frame to the C-terminal 68 amino acids of ICP27. Previous studies
      demonstrated that this hybrid gene, designated as ICP22/ICP27. was expressed
      abundantly at both the mRNA and the protein levels in DI particle-enriched
      infections, but not in standard EHV-1 infection (Chen et al., 1996 J. Virol. 70,
      313-320). Since the ICP22/ICP27 hybrid protein contains portions of two EHV-1
      early regulatory proteins, its effect on EHV-1 gene regulation was investigated.
      In EHV-1-infected cells, the ICP22/ICP27 hybrid protein expressed from plasmid
      vectors significantly reduced expression of a reporter gene under the control of
      the EHV-1 immediate-early (IE) gene promoter and early gene promoter, such as the
      viral ICP27 gene. In uninfected cells, the ICP22/ICP27 hybrid protein moderately
      down-regulated the IE and ICP22 promoters, up-regulated late gene promoters such
      as IR5, and altered the regulatory function of the IE and 1CP22 proteins in co
      transfected cells. These results demonstrated that DI particles might alter viral
      gene regulation by expression of a unique hybrid gene encoded on the DI particle
      genome.

PMID- 10082388
TI  - Construction and characterization of an equine herpesvirus 1 glycoprotein C
      negative mutant.
AB  - An equine herpesvirus 1 (EHV-1) strain RacL 11 mutant was constructed that
      carries the Escherichia coli LacZ gene instead of the open reading frame encoding
      glycoprotein C (gC). The engineered virus mutant (L11(delta)gC) lacked codons 46
      440 of the 1404 bp gene. On rabbit kidney cell line Rk13 and equine dermal cell
      line Edmin337, the L11(delta)gC virus grew to titers which were reduced by
      approximately 5- to 10-fold compared with wild-type RacL11 virus or a repaired
      virus (R-L11(delta)gC). However, when L11(delta)gC growth properties were
      analyzed on primary equine cells a decrease of viral titers was observed such
      that extracellular L11(delta)gC titers were reduced by 48- to 210-fold compared
      with those of wild-type or repaired virus. Heparin sensitive and heparin
      resistant attachment was assessed by binding studies using radiolabeled virion
      preparations. These studies revealed that EHV-1 gC is important for heparin
      sensitive attachment to the target cell. Similar results were obtained when
      cellular glycosaminoglycan (GAG) synthesis was inhibited by chlorate treatment or
      when cells defective in GAG synthesis were used. L11(delta)gC also exhibited
      significantly delayed penetration kinetics on Rk13 and primary equine cells.
      Infection of mice with L11(delta)gC did not cause EHV-1-related disease, whereas
      mice infected with either RacL11 or R-L11(delta)gC exhibited massive bodyweight
      losses, high virus titers in the lungs, and viremia. Taken together, EHV-1 gC was
      shown to play important roles in the early steps of infection and in release of
      virions, especially in primary equine cells, and contributes to EHV-1 virulence.

PMID- 10082389
TI  - Comparison of the major capsid protein genes, terminal redundancies, and DNA-DNA
      homologies of two New Zealand iridoviruses.
AB  - Molecular comparisons were carried out on two iridoviruses isolated from endemic
      sympatric New Zealand pasture pests. These viruses, Costelytra zealandica
      iridescent virus (CzIV/IV16) and Wiseana iridescent virus (WIV/IV9), belong to
      the same virus genus but it is not known how related they are. The major capsid
      protein (MCP) gene from each virus was located, sequenced, and compared to the
      homologous gene from other iridoviruses. The MCP genes of WIV and CzIV were
      similar to each other (87.9% amino acid similarity) and to other iridovirus MCP
      genes. The MCP genes of both WIV and CzIV were most homologous to the MCP gene
      from Tipula iridescent virus (TIV/IV1), with amino acid similarities of 92.3 and
      88.3% respectively. The genomes of WIV and CzIV were compared to other
      invertebrate iridoviruses using solution DNA-DNA hybridisations. Even after
      reducing the annealing stringency conditions hybridisation ratios never exceeded
      10% indicating there is little sequence conservation between iridovirus genomes.
      Estimates of the size of terminal redundancies were also calculated for these
      viruses using pulsed-field agarose gel electrophoresis. These values ranged from
      0 to 8%. These studies indicate that WIV and CzIV have distinct genomes and that
      the genus Iridovirus is comprised of a group of genetically diverse viruses.

PMID- 10082390
TI  - Fusion of sendai virus with liposome depends on only F protein, but not HN
      protein.
AB  - Sendai virus is able to fuse with liposomes even without virus receptors. To
      determine the roles of envelope protein, hemagglutinin-neuraminidase (HN) and
      fusion (F) protein, in Sendai virus-liposome fusion, we treated the virus with
      proteases and examined its fusion with liposomes and the conditions of HN and F
      protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western
      blotting analysis showed that the virus treated with 150 units/ml of trypsin,
      which inactivated selectively hemolysis activity, maintained intact HN, F and
      partially digested F (32 kDa) protein, while virus treated with 15,000 units/ml
      of trypsin, which inactivated both hemolysis and neuraminidase activity, had only
      a 15-kDa digested HN protein and completely digested F protein. The former fused
      with liposomes, but the latter did not. In the virus treated with chymotrypsin,
      which lost both hemolysis and neuraminidase activity, F protein was intact, while
      HN protein was degraded to 15 kDa; in this case the virus fused with liposomes.
      As the virus with 15-kDa HN protein fused with liposomes and that with 20-kDa
      protein did not, HN protein does not appear to play any role in virus-liposome
      fusion. The virus that fused with liposomes had intact F protein. We conclude
      that Sendai virus-liposome fusion is strongly dependent on the presence of intact
      F protein, but not HN protein.

PMID- 10082391
TI  - Immunological characterization of two major secreted forms of recombinant
      hepatitis B virus e antigens.
AB  - Plasmids containing PCR-amplified hepatitis B virus e antigen (HBeAg) genes
      (HBeAg-MV and HBeAg-SV) were constructed and expressed in E. coli strain
      DH5alpha. The induced intracellular glutathione S-transferase (GST) fusion
      proteins of HBeAg-MV and HBeAg-SV were recovered and purified from bacterial
      lysates by affinity chromatography with glutathione-sepharose beads. The HBeAg-MV
      protein contained an additional 19 amino acids at its amino terminus. These two
      proteins were specifically cleaved from GST by the protease factor Xa and
      recognized by a monoclonal antibody against HBeAg. HBeAg-MV and HBeAg-SV were
      found to be the two major components of the post-modified HBcAg during viral
      infection. The antigenic specificities of the fusion and purified HBeAgs (factor
      Xa-digested) were confirmed by the Abbott HBe enzyme immunoassay (EIA) detection
      system. Sera from patients with confirmed hepatocellular carcinoma (HCC)
      specifically reacted only with HBeAg moiety of fusion proteins. HCC sera bound
      more strongly to the HBeAg-SV protein than to the HBeAg-MV one. This indicates
      that HBeAg-SV is either more antigenic than -MV or is the major target protein
      for the elicitation of antibody production after HBV infection. Thus, the two
      recombinant HBeAgs expressed and obtained in this study are appropriate
      immunological agents for the diagnostic detection of hepatitis B virus infection
      in humans.

PMID- 10082392
TI  - Functional analysis of a transrepressor domain in the hepatitis C virus core
      protein.
AB  - Hepatitis C virus (HCV) is one of the major causative agents of chronic liver
      disease with the potential for development of hepatocellular carcinoma. The
      putative core protein of the virus has many intriguing properties, including
      transcriptional regulation of cellular and unrelated viral promoters. To further
      characterize the transregulatory function, a number of chimeric constructs were
      made by fusion of the core gene to the DNA binding domain of the yeast
      transactivator factor GAL4. The fusion protein exhibited a repressor activity on
      the herpes simplex virus thymidine kinase promoter via the upstream GAL4 DNA
      binding sites. A structure /function analysis of HCV core mutants in the context
      of the GAL4 DNA binding domain revealed that the transcriptional repressor
      activity was located near the N-terminus (amino acids 26 85). Transcription was
      strongly inhibited upon transfer of this repressor domain to a heterologous
      activation domain, (3CGln) of Epstein Barr virus transcription factor EBNA3C.
      Results from this study suggest that the HCV core protein contains an overall
      repressor activity, and that the repressor domain is located near the N-terminus.

PMID- 10082393
TI  - Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East
      Russia.
AB  - Seroepizootiologic surveys among wild rodents were carried out in Japan and Far
      East Russia in 1995 and 1996. Seropositive animals were only identified in
      Clethrionomys rufocanus (23/134) in Hokkaido, Japan. On the other hand,
      seropositives were identified in C. rufocanus (1/8), Apodemus agrarius (2/66),
      Apodemus spp. (2/26) and Microtus fortis (3/22) in Vladivostok, Far East Russia.
      Total RNA was isolated from lungs of seropositive animals and the S genome
      segments were amplified by PCR, cloned and sequenced. The S and M genomes of
      hantavirus, derived from Japanese C. rufocanus (Tobetsu genotype), were most
      closely related with Puumala viruses (76-79% nucleotide and 95% amino acid
      identities for S genome, 70-78% nucleotide and 87-92% amino acid identities for M
      genome). The recombinant nucleocapsid protein of Tobetsu genotype was
      antigenically quite similar with that of Sotkamo. These suggest that the virus
      endemic in Japanese C. rufocanus belongs to Puumala virus. Phylogenetic analysis
      indicates that the genotype forms a distinct lineage within Puumala viruses.
      Partial S segment (1-1251 nt), derived from seropositive M. fortis in
      Vladivostok, was sequenced and analyzed. The S genome segment, which was
      designated Vladivostok genotype, was most closely related with Khabarovsk virus
      (79% nucleotide and 90% amino acid identities) which was isolated from M. fortis.

PMID- 10082394
TI  - Genomic and phylogenetic characterization of coxsackievirus B2 prototype strain
      Ohio-1.
AB  - The human picornavirus coxsackievirus B2 (CVB2) is often linked to several
      infections, from mild respiratory diseases to more severe illnesses such as
      myocarditis. In this study, we report the complete genome sequence of CVB2
      prototype strain Ohio-1. The genome sequence was determined from reverse
      transcribed viral RNA, amplified with long distance PCR and used for non
      radioactive sequencing. The full length PCR amplicons were used for in vitro
      transcription and the obtained cRNA was lipofected onto green monkey kidney
      cells, in order to confirm that the PCR generated sequence reflects a viable
      virus RNA. The CVB2 genome sequence shows a typical enterovirus genome
      organization with a total length of 7411 nucleotides. Phylogenetic analysis,
      using the CVB2 polyprotein in comparison with other enterovirus polyproteins,
      clearly shows that CVB2 clusters with the coxsackievirus B-like enteroviruses and
      is more related to coxsackievirus B4 (CVB4) than any other published CVB
      serotype. The grouping of CVB2 and CVB4 as one subgroup has earlier been reported
      in connection with receptor usage and ability to replicate in different cell
      lines. The exposed viral capsid proteins of CVB2 (VP1-VP3) show high similarity
      to other CVB proteins, except in regions that are likely to be surface epitopes.

PMID- 10082395
TI  - The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1,
      CD49a/CD29) is primarily a collagen IV receptor on malignant T cells.
AB  - Several of the beta1 integrin receptors [very late antigen (VLA) molecules] for
      extracellular matrix (ECM) proteins are expressed by malignant T cells in
      cutaneous T-cell lymphoma (CTCL). We evaluated the function of VLA-1, a beta1
      integrin specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+
      leukemic T cells Jurkat line). We found that Jurkat cells adhere significantly to
      collagens only after their activation with phorbol 12-myristate 13-acetate (PMA).
      However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells
      selected for expressing increased levels of VLA-1 (with unchanged levels of VLA
      2, the second collagen integrin receptor) was significantly enhanced relative to
      that of "VLA-1 low" cells. Monoclonal antibody (mAb) 1B3.1, directed against the
      collagen binding domain of VLA-1, inhibited adhesion to collagen IV and to
      collagen I by 36.67%+/-5.25% and 18%+/-4.32%, respectively (p<0.05), whereas the
      inhibition by anti-VLA-2 mAb PIE6 was comparable on both collagens (25%+/-7.48%
      and 36.3%+/-0.94%, respectively; p<0.09). Immuno-histochemical studies of skin
      biopsies from 10 untreated MF patients showed that in all cases at least 10% of
      the lymphocytes residing in the epidermis are VLA-1+VLA-2-. While not directly
      applicable to MF, the demonstrated functions of VLA-1 in leukemic Jurkat cells,
      together with its expression in MF skin, suggest a role for VLA-1 integrins in
      epidermotropism in a small proportion of leukemic MF cells.

PMID- 10082396
TI  - Apoptosis, Fas and Fas-ligand expression in melanocytic tumors.
AB  - Impaired regulation of apoptosis is known to be associated with the development
      of various forms of cancer. Fas binding to its ligand, Fas ligand (Fas-L), has
      been shown to trigger apoptosis in various cell types. Fas-L is expressed by
      melanoma cells and has been suggested to play a role in melanoma escape from
      immune surveillance. In the present study, we assessed apoptotic activity and
      examined Fas and Fas-L expression in malignant melanomas, Spitz nevi and ordinary
      melanocytic nevi. We evaluated apoptotic activity using terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick end labeling. Apoptotic activity was found
      to be minimal in melanomas and moderate in Spitz nevi. In contrast, common nevi
      demonstrated significant levels of apoptosis in the deep parts of the tumor. Fas
      was found to be expressed by all Spitz nevi, most melanocytic nevi and
      approximately half of the malignant melanoma specimens. Fas expression was also
      significantly more pronounced in Spitz nevus cells as compared with the two other
      tumors. The anti-Fas-L antibody was found to stain all three melanocytic tumors.
      Staining was shown to be stronger and more frequent in melanoma cells as compared
      to the nevus cells. Using the Spearman test, no significant correlation between
      Fas-L expression in melanoma cells and apoptosis in MM-infiltrating mononuclear
      cells was found, suggesting that Fas-L expression in melanoma cells may not be
      instrumental in their ability to escape immune mechanisms of defense. In
      contrast, increased levels of apoptosis in the deep parts of melanocytic nevi may
      reflect and possibly contribute to their benign nature.

PMID- 10082397
TI  - Ultrastructural and immunohistochemical studies of the periendothelial matrix in
      human melanoma: evidence for an amorphous matrix containing laminin.
AB  - Angiogenesis and the extracellular matrix are fundamental to tumor progression
      from in situ to invasive and metastatic disease. Laminin, a major glycoprotein
      integrated into basement membranes, is observed in angiogenesis and
      tumorigenesis. A recent study described an association between melanoma cells and
      endothelial cells via an amorphous matrix containing laminin. In the current
      study, we have examined 45 cases of human primary and metastatic melanomas by
      electron microscopy for the presence of an amorphous matrix. We observed an
      amorphous matrix without a clearly delineated lamina or basement membrane in 41
      of the 45 melanomas studied. 28 cases with tissue blocks available for study were
      examined by immunohistochemistry for the expression of laminin and type IV
      collagen. We observed the presence of an angiocentric matrix containing laminin
      in 24 of the 28 melanomas studied. Since laminin is involved in tumor migration,
      the presence of laminin between melanoma cells and small vessels suggests a role
      for this material in periendothelial tumor migration. However, further study is
      required to characterize the nature of this material and the mechanisms involved.

PMID- 10082398
TI  - Dysplastic changes in different types of melanocytic nevi. A unifying concept.
AB  - We observed histopathologic changes previously described in dysplastic
      melanocytic nevi in association with a dermal component characteristic of other
      types of melanocytic nevi or overlapping with features of other varieties of
      nevi. In order to determine the frequency of these changes, we studied 2,164
      cases of compound melanocytic nevi that fulfilled the histopathologic criteria
      for the diagnosis of compound dysplastic nevus, including architectural pattern,
      cytologic features, and mesenchymal changes. Of the 2,164 compound dysplastic
      melanocytic nevi, 1,895 (87.6%) had the histopathologic characteristics
      previously described for dysplastic nevus, 179 (8.3%) showed a dermal component
      with a congenital pattern, 67 (3.1%) demonstrated epidermal and dermal
      characteristics of Spitz's nevus, 8 (0.3%) had features of a combined blue nevus,
      13 (0.6%) had a halo phenomenon and 2 (0.1%) showed dermal neuronevus. By
      considering these nevi as variants of dysplastic nevi, one may apply a unified
      conceptual basis for their nomenclature. In order to completely describe the
      appearance of the nevus, we named them by adding the term "dysplastic", to their
      main histopathologic subtype. Accordingly, six different varieties of dysplastic
      nevi were identified: 1) dysplastic nevus (original); 2) dysplastic nevus with a
      congenital pattern; 3) dysplastic Spitz's nevus; 4) dysplastic combined blue
      nevus; 5) dysplastic halo nevus; and 6) dysplastic neuronevus. In summary, we
      conclude that the histopathologic criteria previously reported for the diagnosis
      of dysplastic nevi may be found in association with a dermal component
      characteristic of other types of melanocytic nevi or may have overlapping
      features with other variants of nevi.

PMID- 10082399
TI  - Immunohistochemical analysis of cytokeratin expression in multiple eccrine
      hidrocystoma.
AB  - The histologic diagnosis as eccrine hidrocystoma may contain some other cysts
      which do not originate from the eccrine sweat glands. Some authors have suggested
      that true eccrine hidrocystoma does not exist. However, multiple eccrine
      hidrocystoma (Robinson type) is a distinct clinical entity which is characterized
      by multiple translucent papules around the eyelids which appear in warm weather.
      Cytokeratin expression in 8 cases of multiple type of unequivocal eccrine
      hidrocystoma was analyzed immunohistochemically. Immunoreactivities in our cases
      were similar to those of eccrine dermal ducts. Therefore, we confirmed that these
      tumors were derived from the eccrine dermal duct, not from the other appendages,
      and that true eccrine hidrocystoma exists.

PMID- 10082400
TI  - Lichenoid and subacute cutaneous lupus erythematosus-like dermatitis associated
      with antihistamine therapy.
AB  - The authors report the occurrence of lichenoid and/or subacute lupus
      erythematosus-like eruptions in a group of patients receiving agents with
      antihistaminic properties. In 1 of the patients the eruption clinically resembled
      lichen planus, while in 5 patients the eruption resembled subacute cutaneous
      lupus erythematosus (SCLE). At a light microscopic level all cases showed a
      lichenoid dermatitis and in 4 cases the lesions were interpreted as representing
      subacute lupus-like eruptions by virtue of the presence of alternating cell poor
      and lichenoid interface dermatitis, suprabasilar lymphocytosis around
      degenerating keratinocytes, and dermal mucinosis. Despite the resemblance at a
      clinical and light microscopic level to SCLE, anti-Ro seropositivity could not be
      established in any of the cases. One case, however, did demonstrate antihistone
      antibodies in concert with a high antinuclear antibody titer. A causal
      association was implicated by virtue of lesional resolution following drug
      withdrawal. The association of cutaneous eruptions resembling SCLE with
      antihistamine intake is seemingly a novel one. The possible pathogenetic basis of
      the eruptions is discussed.

PMID- 10082401
TI  - Histopathology of an adverse reaction to a eutectic mixture of the local
      anesthetics lidocaine and prilocaine.
AB  - A unique histopathologic reaction to the topical application of a eutectic
      mixture of the local anesthetics lidocaine and prilocaine (EMLA), used for
      topical anesthesia prior to biopsy in two children is described. Standard
      application of EMLA cream under occlusion for 1 h was given to both patients. The
      biopsies in both cases demonstrate focal vacuolization of the upper spinous and
      granular layers. The epidermis was focally separated from the dermis in areas of
      basal vacuolar alteration. Electron microscopy performed in one case demonstrated
      the dermal-epidermal cleft to be secondary to alteration of the basal cells with
      condensation of the cytoplasm and cytologic degeneration similar to that seen in
      epidermolysis bullosa simplex.

PMID- 10082402
TI  - Inflammatory metastatic melanoma.
AB  - An 87-year-old woman developed erythema, induration and tenderness of the skin
      overlying each breast. One year before, she had undergone an axillary lymph node
      dissection because of metastases from melanoma. The primary site was unknown. A
      skin biopsy showed pigmented tumor nests within the dermal lymphatic vessels, and
      immunohistochemistry confirmed the melanocytic origin. The diagnosis of
      inflammatory metastatic melanoma was made.

PMID- 10082403
TI  - Folliculo-sebaceous cystic hamartoma is but the sebaceous end of tricho-sebo
      folliculoma spectrum.

PMID- 10082404
TI  - Premedication, preparation, and surveillance.
AB  - During the last two years, the well-known positive role of benzodiazepines
      (midazolam and diazepam) in conscious sedation, both in adults and pediatric
      patients, has been confirmed by several studies. However, problems concerning the
      role of sedation and analgesia in nonoperative endoscopy are still a matter of
      debate. Particular attention has focused on attempts to identify the "ideal
      candidate" for conscious sedation, and on the importance of providing patients
      with information before the procedure, which should be matched to each patient's
      style of coping. Before detailed information about a medical procedure is given
      blindly, the clinician should investigate whether such information will benefit
      or adversely affect the patient receiving it. An important aspect of the sedation
      procedure is the prevention of hypoxia and cardiopulmonary complications. Recent
      endoscopic experience has provided little additional information concerning the
      well-known risk of oxygen desaturation during conscious sedation. Performing
      endoscopy in sedated patients reduces, but does not eliminate, the risk of
      hypoxia. Some independent variables capable of predicting severe desaturation
      have been recognized, such as basal SaO2 < 95%, respiratory disease, more than
      one attempt needed for intubation, emergency procedure, and an American Society
      of Anesthesiologists score of III or IV. As far as preparation is concerned, some
      light has been cast by a meta-analysis of available studies concerning the role
      of sodium phosphate and polyethylene glycol electrolyte lavage solution (PEG
      ELS). The former preparation has been found to be as effective and less costly
      compared with the latter. In particular, sodium phosphate may be preferable in
      patients without cardiovascular or renal co-morbidity, and in those with a
      tendency to develop nausea or bloating.

PMID- 10082405
TI  - Reflux disease and Barrett's esophagus.
AB  - Gastroesophageal reflux disease (GERD) is a common clinical problem. New
      information suggests that infection with Helicobacter pylori may protect patients
      from developing GERD and its complications. Endoscopy may be used by clinicians
      to tailor GERD therapy, but an empirical trial of a proton-pump inhibitor may be
      an alternative diagnostic approach. Studies continue to show that laparoscopic
      antireflux surgery is a cost-effective treatment option for patients requiring
      maintenance therapy with proton-pump inhibitors. However, the minimally invasive
      nature of the operation should not alter the indications for antireflux surgery,
      especially for patients with atypical symptoms. It remains unclear why some
      patients with GERD develop Barrett's esophagus, whereas others do not. Recent
      guidelines suggest that patients with long-standing GERD symptoms, especially
      white men over 50 years of age, should undergo endoscopy at least once to screen
      for Barrett's esophagus. Debate concerning short-segment Barrett's esophagus
      continues. Intestinal metaplasia at a normal-appearing gastroesophageal junction
      may be associated with intestinal metaplasia of the stomach and infection with H.
      pylori, whereas short tongues of intestinal metaplasia in the esophagus are
      associated with GERD. Cancer surveillance is indicated in short-segment Barrett's
      esophagus, as dysplasia may develop in these patients. Barrett's esophagus is the
      only known risk factor for the development of esophageal adenocarcinoma, but the
      incidence of adenocarcinoma may be lower than previously reported. New clinical
      guidelines for endoscopic surveillance suggest that the surveillance interval
      should be lengthened to every two years in patients without dysplasia. Newer
      treatment options, such as thermal ablation and photodynamic therapy, continue to
      show promise, but are not yet ready for routine clinical use.

PMID- 10082406
TI  - Ulcers and nonvariceal bleeding.
AB  - This review of nonvariceal upper gastrointestinal bleeding concentrates mainly on
      peptic ulcer bleeding, and is based on papers published during the last two
      years. While the focus is on outcome prediction models and therapeutic
      interventions, brief reference is also made to certain epidemiological aspects,
      pathological and animal studies, and risk factors for bleeding peptic ulcer.

PMID- 10082407
TI  - Variceal bleeding and portal hypertension: still a therapeutic challenge?

PMID- 10082408
TI  - Diagnosis of esophagogastric tumors: a trend toward virtual biopsy.

PMID- 10082409
TI  - Treatment of esophageal and gastric tumors.
AB  - Endoscopic mucosal resection (EMR) has gained increasing popularity in the
      treatment of esophageal and gastric mucosal cancers in Japan, for complete local
      resection of the cancer-bearing mucosa. In Western countries, the concept of
      mucosal cancer and the necessity of treating it are gradually but steadily coming
      to be accepted. As a treatment for inoperable cases of advanced cancer, on the
      other hand, intubation with self-expanding metal stents has been widely accepted
      as a less invasive form of palliation for malignant obstruction of the upper
      gastrointestinal tract. Tumor ingrowth into the stent can be mechanically avoided
      by adding a membrane coating to it. In the last two years, applications for
      therapeutic endoscopy in the treatment of esophageal and gastric tumors have
      continued to widen.

PMID- 10082410
TI  - Small-bowel endoscopy.
AB  - An overview of the scientific literature on small-bowel enteroscopy demonstrates
      that sonde enteroscopy is becoming more and more limited in its indications. Push
      enteroscopy is now a well-accepted modality for evaluation of the patient with
      small-bowel disease, including those with undiagnosed causes for gastrointestinal
      bleeding, various types of malabsorption, and radiological abnormalities.
      Intraoperative enteroscopy has very specific indications, and there is a high
      rate of positive findings. It appears that an enterotomy with passage of a
      shorter, more maneuverable enteroscope is an acceptable way to evaluate the small
      bowel, although use of a sonde enteroscope may be an innovative method for
      intraoperative enteroscopy. In the evaluation of patients with iron-deficiency
      anemia or occult gastrointestinal bleeding in whom colonoscopy is negative, it is
      evidently more cost-effective to use a dedicated push enteroscope early on. The
      use of two different instruments--a gastroscope followed by a dedicated push
      enteroscope--is more expensive, and probably does not increase the yield for
      pathology. Many lesions that are responsible for obscure bleeding are actually
      located within reach of an upper intestinal endoscope, but are not recognized.
      This is probably due to inexperience on the part of the original endoscopist, who
      may see the pathology, but does not invoke it as the cause for bleeding. Outcome
      studies are now being performed, and there are some interesting considerations
      for combination hormonal therapy in patients with recurrent obscure bleeding,
      which most likely emanates from small-bowel arteriovenous malformations.

PMID- 10082411
TI  - Colon polyps and cancer.
AB  - A number of recent publications dealing with colon polyps and cancer emphasize
      cost-effectiveness and the outcomes of screening and follow-up surveillance of
      high-risk groups. These groups include patients with either a past personal
      history or a family history of colorectal adenomas or cancer. Several papers
      address the effectiveness and compliance with different methods of screening of
      the asymptomatic, average-risk population for colorectal neoplasia. Other
      important publications deal with colorectal cancer prevention, the natural
      history of the adenoma-carcinoma sequence, diagnosis of polyps and cancer,
      colonoscopic polypectomy, management of the patient with a malignant polyp, and
      endoscopic treatment of obstructing cancer.

PMID- 10082412
TI  - Inflammatory bowel disease.
AB  - The causes of inflammatory bowel disease (IBD) continue to be an enigma. The
      incidence has stabilized in Western countries. Involvement of the upper
      gastrointestinal tract has been found in a high percentage of patients, and can
      be used to guide the work-up in patients with abdominal complaints. Ileoscopy
      must be added to the routine investigation when a suspicion of IBD exists. A
      number of new methods have been proposed, in particular Doppler sonography and
      magnifying chromoscopy, but their clinical contribution remains to be determined.
      Carcinoma surveillance is still the major diagnostic problem. New methods are
      available but need to be evaluated, particularly in patients at increased risk,
      such as those with primary sclerosing cholangitis.

PMID- 10082413
TI  - Diagnostic endoscopic retrograde cholangiopancreatography.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is still a gold standard in
      the diagnostic work-up of the pancreaticobiliary system. However, the problem of
      post-ERCP pancreatitis has not yet been solved. Since the appearance of magnetic
      resonance cholangiopancreatography (MRCP), there has been a trend for it to
      replace ERCP as an imaging tool. At present, MRCP equipment is not available at
      every institution. In addition, MRCP images are not satisfactorily comparable to
      those provided by ERCP, although technological advances will fill this gap in the
      near future. If this is achieved, diagnostic ERCP may be reduced to the specific
      tasks of obtaining histological and cytological materials, and for functional
      studies.

PMID- 10082414
TI  - Therapeutic biliary endoscopy.
AB  - Therapeutic biliary endoscopy continues to evolve; some small but important
      developments were seen during the last year. Competing technologies are
      continuing to develop.

PMID- 10082415
TI  - Therapeutic pancreatic endoscopy.
AB  - Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has established
      itself as a valuable tool for the treatment of a variety of biliary tract
      disorders. Fueled by an ever-increasing demand for minimally invasive therapy,
      pancreatic endoscopy was the logical frontier for expansion of therapeutic ERCP.
      Endoscopic treatment of benign pancreatic disorders can be a cost-effective
      alternative to more invasive radiological or surgical methods. Conditions such as
      acute and chronic pancreatitis, pancreatic calculi, and pseudocysts can in many
      cases be managed endoscopically. This review summarizes the current state of the
      art in therapeutic pancreatic endoscopy.

PMID- 10082416
TI  - Endoscopic ultrasonography.
AB  - Areas of application for endosonography can be roughly divided into three
      categories: standard diagnostic examination; operative diagnostic examination
      (fine-needle aspiration); and operative therapeutic procedures. Nevertheless,
      endoscopic ultrasonography remains a single technique, in which the physician can
      not only raise a suspicion of a particular disease, but can also obtain
      cytological confirmation when needed and carry out a therapeutic procedure when
      indicated. Widely accepted indications for endosonography are the staging of
      esophageal and rectal cancer, and the visualization of submucosal lesions and
      gastric wall diseases; other indications, such as imaging of the pancreas and
      biliary tree, are still being discussed.

PMID- 10082417
TI  - Diagnostic laparoscopy: an update.
AB  - With new technical advances, wider availability, and the recent proliferation of
      less invasive surgery, the use of diagnostic laparoscopy has expanded far beyond
      its traditional role in the evaluation of chronic liver disease. Short of open
      laparotomy, diagnostic laparoscopy is the most accurate modality for staging of
      intra-abdominal malignancies, and is particularly well-suited for patients who
      otherwise would not require surgical palliation. In addition to avoiding
      unnecessary laparotomy in this group, diagnostic laparoscopy has proved valuable
      in the assessment of abdominal trauma, acute abdomen, and ischemic bowel disease.
      We briefly review here some of the new developments in the field of diagnostic
      laparoscopy.

PMID- 10082418
TI  - Minimally invasive surgery.

PMID- 10082419
TI  - Brefeldin A (BFA) disrupts the organization of the microtubule and the actin
      cytoskeletons.
AB  - Previous inquiries into the effects of Brefeldin A (BFA) have largely
      concentrated on dynamics of ER-Golgi membrane traffic, predominantly after
      relatively short treatments with the drug. We have now analyzed the effects of
      long BFA treatment on overall cell morphology, behavior of resident and cycling
      Golgi proteins, and microtubular and actin cytoskeletons organization. Prolonged
      (15 h or 40 h) treatment of normal rat kidney (NRK) cells with BFA caused
      dramatic swelling of the Endoplasmic Reticulum (ER) and shifted its localization
      to the periphery of the cells. The Golgi complex was disassembled and Golgi
      proteins redistributed and persisted in partially distinct compartments.
      Prolonged BFA treatment resulted in marked disruption of the MT and actin
      cytoskeleton. Peripheral MT were absent and tubulin staining was concentrated in
      short astral MT emanating from the microtubule organizing center (MTOC). Actin
      stress fibers were largely absent and actin staining was concentrated within a
      perinuclear area. Within this region, actin localization overlapped that of the
      membrane transport factor p115. BFA effects on Golgi structure and on MT and
      actin organization showed the same threshold -- all could be partially reversed
      after 30 min and 15 h BFA treatment but were irreversible after 40h incubation
      with the drug. The observed effects were not induced by signaling pathways
      involved in apoptotic phenomena or in ER stress response pathways. These results
      suggest that BFA inhibits the activity of key molecules that regulate MT and
      actin cytoskeleton dynamics. The findings can be used as the basis for
      elucidating the molecular mechanism of BFA action on the cytoskeleton.

PMID- 10082420
TI  - Monoclonal antibody ID5: epitope characterization and minimal requirements for
      the recognition of polyglutamylated alpha- and beta-tubulin.
AB  - A monoclonal antibody (ID5) raised against the synthetic tetradecapeptide
      corresponding to the C-terminal region of detyrosinated alpha-tubulin showed an
      unexpected cross-reactivity with beta-tubulin from pig brain tissue. The
      specificity and the minimal epitope requirements of ID5 were characterized by
      competitive enzyme-linked immunosorbent assay (ELISA) and spot blots using a
      series of synthetic peptides and the natural peptides of beta-tubulin and
      detyrosinated alpha-tubulin from brain. The epitope of ID5 is comprised of the
      carboxyterminal sequence -XEE carrying the terminal alpha-carboxylate group with
      X being a variable residue. All linkages in the epitope involve alpha-peptide
      bonds. This epitope is provided by the detyrosinated alpha-tubulin main chain and
      the polyglutamyl side chains of both brain alpha- and beta-tubulins. Affinity
      purification of beta-tubulin peptides and mass spectrometric characterization
      reveal that peptides carrying three to nine glutamyl residues in the side chain
      are recognized by ID5. These results show that except for the first gamma-peptide
      linkage the alpha-peptide bond is the preferred linkage type in the tubulin
      polyglutamyl side chains.

PMID- 10082421
TI  - Subunits of the eukaryotic cytosolic chaperonin CCT do not always behave as
      components of a uniform hetero-oligomeric particle.
AB  - The chaperonin CCT is an hetero-oligomeric molecular chaperone complex. Studies
      in yeast suggest each of its eight gene products are required for its major
      identified functions in producing native tubulins and actins. However, it is
      unclear whether these eight components always form a single particle, covering
      all functions, or else can also exist as heterogeneous mixtures and/or free
      subunits in cells. Using mouse P19 embryonal carcinoma cells, which divide
      rapidly, yet in retinoic acid adopt a neuronal phenotype, admixed with occasional
      (approximately 10%) fibroblast-like cells, together with a panel of peptide
      specific antibodies raised to 7 of the 8 CCT subunits we show that; (1) adoption
      of a post mitotic phenotype is accompanied by reduced CCT protein expression,
      significantly more so for CCTbeta, CCTdelta, CCTepsilon, and CCTtheta than for
      CCTalpha (TCP-1), CCTgamma and CCTzeta; (2) CCTalpha is detected preferentially
      over other subunits in neurites of P19 neurons; (3) small amounts of CCTalpha and
      gamma are localised in nuclei (i.e. are not exclusively cytoplasmic), selectively
      so compared with other subunits; (4) numerous cytosolic foci exist in the
      cytoplasm which, when detected by double immunofluorescence can contain only one
      of the subunits probed for; (5) while a "core" chaperonin particle can be
      immunoprecipitated under native conditions, epitope access is modified both by
      nucleotides and by non-CCT co-precipitating proteins. Collectively, these
      findings indicate that CCT subunits are not only components of the hetero
      oligomeric chaperonin particle but exist as significant populations of free
      subunits or smaller oligomers in cells.

PMID- 10082422
TI  - A role for phosphorylation in the dynamics of keratin intermediate filaments.
AB  - Keratins undergo highly dynamic events in the epithelial cells that express them.
      These dynamic changes have been associated with important cell processes. We have
      studied the possible role of keratin phosphorylation-dephosphorylation processes
      in the control of these dynamic events. Drugs that affect the protein
      phosphorylation metabolism (activators or inhibitors of protein kinases or
      protein phosphatases) have been used in two different dynamic experimental
      systems. First, the behaviour of keratins after the formation of cell
      heterokaryons, and second, the assembly of a newly synthesised keratin after
      transfection into the pre-existing keratin cytoskeleton. The main difference
      between these two systems stems on the alteration of the amount of keratin
      polypeptides present in the cells, since in heterokaryons this amount was
      unaltered whilst in transfection experiments there is an increase due to the
      presence of the transfected protein. We observed in both systems that the
      inhibition of protein kinases led to a delayed dynamic behaviour of the keratin
      polypeptides. On the contrary, the inhibition of protein phosphatases by okadaic
      acid or the activation of protein kinases by phorbol esters promoted a
      substantial increase in the kinetics of these processes. Biochemical studies
      demonstrate that this behavioural changes can be correlated with changes in the
      phosphorylation state of the keratin polypeptides. As a whole, present results
      indicate that the highly dynamic properties of the keratin polypeptides can be
      modulated by phosphorylation.

PMID- 10082423
TI  - Paracrine or virus-mediated induction of decorin expression by endothelial cells
      contributes to tube formation and prevention of apoptosis in collagen lattices.
AB  - Resting endothelial cells express the small proteoglycan biglycan, whereas
      sprouting endothelial cells also synthesize decorin, a related proteoglycan. Here
      we show that decorin is expressed in endothelial cells in human granulomatous
      tissue. For in vitro investigations, the human endothelium-derived cell line,
      EA.hy 926, was cultured for 6 or more days in the presence of 1% fetal calf serum
      on top of or within floating collagen lattices which were also populated by a
      small number of rat fibroblasts. Endothelial cells aligned in cord-like
      structures and developed cavities that were surrounded by human decorin. About
      14% and 20% of endothelial cells became apoptotic after 6 and 12 days of co
      culture, respectively. In the absence of fibroblasts, however, the extent of
      apoptosis was about 60% after 12 days, and cord-like structures were not formed
      nor could decorin production be induced. This was also the case when lattices
      populated by EA.hy 926 cells were maintained under one of the following
      conditions: 1) 10% fetal calf serum; 2) fibroblast-conditioned media; 3)
      exogenous decorin; or 4) treatment with individual growth factors known to be
      involved in angiogenesis. The mechanism(s) by which fibroblasts induce an
      angiogenic phenotype in EA.hy 926 cells is (are) not known, but a causal
      relationship between decorin expression and endothelial cell phenotype was
      suggested by transducing human decorin cDNA into EA.hy 926 cells using a
      replication-deficient adenovirus. When the transduced cells were cultured in
      collagen lattices, there was no requirement of fibroblasts for the formation of
      capillary-like structures and apoptosis was reduced. Thus, decorin expression
      seems to be of special importance for the survival of EA.hy 926 cells as well as
      for cord and tube formation in this angiogenesis model.

PMID- 10082424
TI  - Activation of NF-kappaB is necessary for the restoration of the barrier function
      of an epithelium undergoing TNF-alpha-induced apoptosis.
AB  - Tumor necrosis factor-alpha (TNF) induces apoptosis in confluent LLC-PK1
      epithelial cells, but also activates NF-kappaB, a negative regulator of
      apoptosis. The presence of increased TNF-induced apoptosis causes a transient
      increase in epithelial permeability, but the epithelial barrier function
      recovers, as assessed by measuring the transepithelial electrical resistance, the
      paracellular flux of mannitol and by the electron microscopic evaluation of the
      penetration of the electron-dense dye ruthenium red across the tight junctions.
      The integrity of the epithelial cell layer is maintained by rearrangement of non
      apoptotic cells in the monolayer and by the phagocytosis of apoptotic fragments.
      To study the role of NF-kappaB in an epithelium exposed to TNF, NF-kappaB was
      inhibited in LLC-PK1 epithelial cells with either the dietary compound, curcumin,
      or by transfection with a dominant negative mutant inhibitor I kappaB alpha.
      Replacement of serine 32 and 36 by alanine has been shown to prevent its
      phosphorylation and degradation, blocking NF-kappaB activation. Inhibition of NF
      kappaB altered the morphology of TNF-induced apoptotic cells, which showed lack
      of fragmentation and membrane blebbings, and absence of phagocytosis by
      neighboring cells. TNF treatment of NF-kappaB-inhibited cells also caused altered
      distribution of the tight junction-associated protein ZO-1, increased epithelial
      leakiness, and impaired the recovery of the epithelial barrier function, which
      normally occurs 6 hours after TNF treatment of LLC-PK1 cells. These data
      demonstrate that NF-kappaB activation is required for the maintenance of the
      barrier function of an epithelium undergoing TNF-induced apoptosis.

PMID- 10082425
TI  - Immunolabeling analysis of biosynthetic and degradative pathways of cell surface
      components (glycocalyx) in Paramecium cells.
AB  - Biosynthetic and degradative pathways of glycocalyx components are largely
      unknown in Paramecium and in some related parasitic protozoa. We isolated cell
      surface (glyco-)proteins, i.e., surface antigens (SAg) and used them in the
      native (nSAg) or denatured (dSAg) state to produce antibodies (AB) for
      immunolocalization by confocal imaging and by quantitative immunogold EM-labeling
      of ultrathin sections or of freeze-fracture replicas. Antibodies against nSAg or
      dSAg, respectively, yield different labeling densities over individual
      structures, thus indicating biosynthetic or degradative pathways, respectively.
      We derive the following biosynthetic way: ER --> Golgi apparatus --> non
      regulated/non-dense core vesicle transport --> diffusional spread over non
      ciliary (somatic) and ciliary cell membrane. For degradation we show the
      following pathways: Concentration of nSAg in the cytostome --> nascent digestive
      vacuole --> mature vacuoles --> release of dSAg at cytoproct, with partial
      retrieval by "discoidal vesicles". A second internalization pathway proceeds via
      coated pits ("parasomal sacs") --> early endosomes ("terminal cisternae") -->
      digestive vacuoles. Dense packing of SAg in the glycocalyx may drive them into
      the endo-/phagocytic pathway. Still more intriguing is the site of nSAg
      integration into the cell membrane by unstimulated exocytosis. We consider
      unconspicuous clear vesicles relevant for nSAg export, probably via sites which
      most of the time are occupied by coated pits. This could compensate for membrane
      retrieval by coated pits, while scarcity of smooth profiles at these sites may be
      explained by the much longer time period required for coated pit formation as
      compared to exocytosis.

PMID- 10082426
TI  - Molecular studies of trophoblast HLA-G: polymorphism, isoforms, imprinting and
      expression in preimplantation embryo.
AB  - There is considerable interest in human HLA-G arising from the observation that
      it is expressed selectively on the surface of extravillous trophoblast, the fetal
      cell population directly in contact with the mother. We investigated several
      aspects of the molecular biology of this unusual molecule. Limited polymorphism
      at the nucleotide level, and even more restricted variation at the amino acid
      level, was found in our Caucasian population. A further unusual aspect of HLA-G
      is the occurrence of alternatively spliced mRNAs. Spliced messages that could
      give rise to either membrane-bound or soluble proteins have been reported and six
      of these alternative forms were detected in all first trimester and term
      placentae, highly purified villous and extravillous trophoblast and the cell
      lines, JEG-3 and 221-G. An additional novel splice variant involving loss of part
      of the 3'-untranslated region was observed with two alleles. Using a sensitive
      RNase protection assay higher levels of the membrane-bound RNAs as compared to
      the soluble forms were detected in first trimester and term placentae as well as
      in JEG-3. Contrary to previous findings our term samples taken from the maternal
      aspect showed higher levels of both mRNA species when compared to first trimester
      placenta. The question of imprinting was addressed through the detection of
      heterozygotes both in placental tissue and, more tellingly, in the purified
      trophoblast cells. There was no evidence of imprinting. In addition we did not
      find mRNA for HLA-G in human two to eight-cell embryos or in blastocyst or in
      sperm samples.

PMID- 10082427
TI  - Detection of soluble HLA-G molecules in plasma and amniotic fluid.
AB  - Although the cDNA sequence of HLA-G antigens is compatible with their expression
      as soluble molecules (sHLA-G), the determination of native sHLA-G levels in body
      fluids has not yet been described. The lack of this information is likely to
      reflect the difficulties in developing an assay suitable to measure sHLA-G
      antigens in the presence of soluble HLA-A, -B and -C (sHLA-I) antigens, since
      most of the available anti-HLA-G mAb do not detect soluble beta2-m associated HLA
      G antigens or crossreact with sHLA-I antigens. Therefore, we have developed a two
      step assay which eliminates the interference of classical HLA class I antigens.
      In the first step, the sample is depleted of sHLA-I antigens and of HLA-E
      antigens with mAb TP25.99. Then, HLA-G antigens are captured with mAb W6/32 and
      detected with anti-beta2-m mAb in ELISA. Utilizing this assay, sHLA-G antigen
      levels were measured in EDTA plasma from 92 controls with known HLA types, 28
      women at delivery and the corresponding cord bloods and in 50 amniotic fluids.
      Mean sHLA-G plasma levels did not differ between males (24.9+/-3.0 SEM ng/ml;
      n=42) and females (20.1+/-2.1 SEM ng/ml; n = 50). However, sHLA-G levels in HLA
      A11 positive probands (mean: 13.0+/-4.4 SEM ng/ml; n=12) were significantly
      (P<0.05) lower than in HLA-A11 negative ones (mean: 24.5+/-2.0 SEM ng/ml; n=80).
      sHLA-G levels in women at delivery (mean: 22.9+/-2.2 SEM ng/ml; n=28) were in the
      range of controls but were significantly (P<0.001) reduced in the corresponding
      cord bloods (mean: 13.8+/-1.5 SEM ng/ml; n=28). sHLA-G levels in amniotic fluids
      (mean: 15.5 + 1.0 SEM ng/ml; n=50) were significantly (P<0.001) lower than in
      plasma. sHLA-G levels were 5 and 11% of those of sHLA-I antigens in plasmas and
      amniotic fluids, respectively. Individual sHLA-G levels were not correlated with
      sHLA-I levels. SDS-PAGE analysis of plasma sHLA-G antigens revealed two molecular
      variants with a 35 kD and a 27 kD MW corresponding to the sizes of sHLA-G1 and 
      G2 isoforms. In conclusion, our study has shown that the two-step assay we have
      developed is reliable in measuring sHLA-G antigen levels. This assay will
      facilitate the analysis of the biological and clinical significance of sHLA-G
      antigens in plasma.

PMID- 10082428
TI  - G10.3 monoclonal antibody identifies novel functional cell surface structures
      expressed by normal B lymphocytes and various malignant cell lines.
AB  - G10.3, a unique monoclonal antibody (mAb), was produced to better characterize
      lymphocyte subsets. In the present study, we show that this mAb identifies 118,
      83 and 51 kDa cell surface sialylated glycoproteins on the immunizing cell line
      YTindi. The reactivity of G10.3 mAb is restricted in normal cells to B
      lymphocytes, whereas within tumoral cell lines various lymphoid and non-lymphoid
      cells were found positive. Interestingly, functional studies revealed that
      triggering G10.3 mAb reactive molecules with soluble antibody led to an
      inhibition of growth and to an induction of programmed cell death in tumor cell
      lines expressing high levels of reactive molecules.

PMID- 10082429
TI  - CD4 segregates into specific detergent-resistant T-cell membrane microdomains.
AB  - In T cells, glycolipids, glycoproteins attached to the membrane via a
      glycosylphosphatidylinositol (GPI) anchor, and Src-like tyrosine kinases are
      highly enriched in a membrane fraction resistant to solubilization by nonionic
      detergents. We have investigated the distribution of CD4 in T-cell membranes and
      found that approximately 10% of the CD4 co-receptor is associated with detergent
      insoluble membrane microdomains, whilst the remaining 90% is in soluble
      membranes. Moreover, approximately 60% of the "insoluble CD4" is present in
      membrane microdomains containing GPI-anchored proteins and high glycolipid
      dependent kinase activity, whereas the remaining 40% displays no association with
      GPI-anchored proteins and lacks glycolipid-associated kinase activity These
      results indicate that CD4 segregates at least into three different membrane
      microenvironments: 1) soluble membranes; 2) insoluble membrane microdomains
      containing GPI-anchored proteins; and 3) insoluble membrane microdomains devoid
      of GPI-anchored proteins. The level of CD4 in insoluble membranes was not
      modified upon triggering activation by T-cell receptor-crosslinking but
      detectable amounts of CD3 subunits were recruited into these specialized
      membranes under those conditions. The physical separation of CD4 into different
      membrane microenvironments raises the possibility of that some of the multiple
      functions of CD4 might segregate into distinct types of lipid microenvironment.
      The fact that components of T-cell receptor/CD3 complex were recruited into
      insoluble membranes upon stimulation is consistent with the CD4 present in this
      membrane fraction might participate in T-cell receptor-triggered activation
      events.

PMID- 10082430
TI  - HLA-A, -B, -C polymorphism in a UK Ashkenazi Jewish potential bone marrow donor
      population.
AB  - To further our knowledge of HLA polymorphism in different ethnic populations and
      to increase the number of full HLA class I typed potential bone marrow donors on
      the Anthony Nolan Bone Marrow Trust register, HLA-A, -B and -C polymorphism was
      characterised in 412 Ashkenazi Jewish potential donors. Serological typings and
      limited molecular analysis was performed for HLA-A and -B, and molecular typings
      were performed for HLA-C. Gene and haplotype frequencies were calculated using
      the maximum likelihood method and compared with UK Caucasoid and other Jewish
      populations. While the specificities identified were in general overlapping with
      the UK Caucasoid data, a difference in the frequencies of individual
      specificities was observed. For example, HLA-B62, a common serotype found in the
      UK Caucasoid population, is almost absent in the Ashkenazim. HLA-A, -C, -B
      haplotype frequencies also differ between the two populations with A26-Cw*1203
      B38 and A24-Cw*04-B35 significant in the Ashkenazim, whilst A1-Cw*07-B8, a common
      Caucasoid haplotype, was found to be less frequent. Overall the results for the
      UK Ashkenazi population were most similar to previous reports on Polish/Russian
      Jews.

PMID- 10082431
TI  - Distribution of HLA gene and haplotype frequencies in Taiwan: a comparative study
      among Min-nan, Hakka, Aborigines and Mainland Chinese.
AB  - A total of 8,497 blood samples were typed for HLA-A, B, DR and DQ. Of these,
      7,137 Min-nan, 714 Hakka, 535 Mainland Chinese (152 from North China, 211 from
      Middle China, and 172 from South China) and 111 Aborigines were randomly selected
      from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). Differences in HLA gene and
      antigen frequencies have been observed between various ethnic groups of the
      Chinese population in Taiwan. The phylogenic tree shows Taiwan Aborigines and
      Javanese cluster together; Min-nan shares a common cluster with Hakka, Southern
      Hans and Thai; and Northern Hans shares a cluster with Middle Hans. The
      separation between Northern/Middle and Southern Chinese Hans support the idea
      that Northern and Southern Chinese have different genetic background. Aborigines
      appeared to be quite distinct in the distribution of a majority of the class I
      and class II antigens. High frequency of HLA-A24 (60.4%) and relatively
      restricted HLA polymorphisms are noted in Aborigines. The HLA haplotypes with
      high frequency in Aborigines included A24-B60-DRB1*04, A24-B60-DRB1*14, A24-B48
      DRB1*04, and A24-B48-DRB1*14, which are different from the other ethnic groups.
      Although the phylogenic tree separates Aborigines and Han Chinese populations, 4
      out of 20 most common HLA-A, -B, and -DR haplotypes presented in both Aborigines
      and Han Chinese may reflect an ancient common origin or intermixture between
      early settlers of Han Chinese and Taiwan Aborigines. The results in this study
      are essentially a summary of the observed gene/haplotype frequencies and
      differences among various ethnic groups in Taiwan.

PMID- 10082432
TI  - HLA-DR, DQ nucleotide sequence polymorphisms in the Pasiegos (Pas valleys,
      Northern Spain) and comparison of the allelic and haplotypic frequencies with
      those of other European populations.
AB  - In general, Northern Spain has remained geographically isolated from neighboring
      Spanish regions for centuries: steep mountains create small isolated and inbred
      population groups with their own characteristic cultures and unique gene pools.
      The Pasiego region forms an area of distinctive characteristics among the people
      living in Northern Spain, although the origin of the inhabitants of the Pas
      valleys (Pasiegos) is not clearly defined. We have studied the MHC class II
      alleles in a large sample of unrelated individuals living in the Pas valleys.
      Allelic and haplotypic frequencies, population distances and their corresponding
      dendrogram, using the N-J method, were used to study the relationships between
      populations. The closest is observed between Pasiegos and Danes, followed by
      other European people in the following decreasing order: Poles, Germans, non
      Pasiego Cantabrians, Belgians, Basques, French, other Spaniards from Madrid,
      Italians, Finns, Croatians, Welsh, Ashkenazi Jews and other Mediterranean
      populations (Greeks, Hungarians, Sardinians and Bulgarians). Particular
      characteristic Northern European alleles are observed with high frequency in the
      Pasiegos and non-Pasiego Cantabrians (DRB1*1501-DQA1*0102-DQB1*0602). The second
      most frequent three-locus haplotype in both populations is DRB1*0701-DQA1*0201
      DQB1*0201. These observations suggest an important mixture of alleles from
      geographically distinct areas. In conclusion, the Pasiegos are typical examples
      of isolated genetic pools in the Iberian Peninsula and allow one to suggest that
      what we call the "Pasiego cluster" can be considered, in many ways, as another
      example of the few deviant groups (e.g. Lapps, Basques and Sardinians) having
      preserved their genetic, social and ethnographic characteristics and, in some
      cases, their ancestral language.

PMID- 10082433
TI  - HLA haplotypes and microsatellite polymorphisms in and around the major
      histocompatibility complex region in a Native American population with a high
      prevalence of scleroderma (systemic sclerosis).
AB  - Choctaw Native Americans in southeastern Oklahoma have the highest prevalence of
      scleroderma or systemic sclerosis yet found (469/100,000). An Amerindian HLA DR2
      haplotype (DRB1*1602) was significantly associated with scleroderma in this
      population in a previous study. It is not known, however, if other disease genes
      are linked to this HLA haplotype. The regions flanking the HLA loci were studied
      with polymorphic microsatellite markers. An extended HLA DR2 (DRB1*1602,
      DQA1*0501, DQB1*0301, DPB1*1301) haplotype that includes the class I and III
      regions was identified which was significantly associated with scleroderma in the
      Oklahoma Choctaw. No other significant associations with microsatellite marker
      alleles immediately flanking the HLA region were found.

PMID- 10082434
TI  - New high resolution typing strategy for HLA-A locus alleles based on dye
      terminator sequencing of haplotypic group-specific PCR-amplicons of exon 2 and
      exon 3.
AB  - In this study, a new sequencing-based typing strategy for the HLA-A locus is
      presented which involves group-specific separate amplification of exon 2 and 3 of
      HLA-A alleles in a first step. Conserved HLA-A locus-specific primers of intron 1
      or 3 were combined in 10 primer-mixes with group-specific primers hybridizing to
      the 5'- or 3'-end of exon 3 or 2 for pre-typing of the HLA-A alleles in 14
      allelic groups. Maximally four overlapping short amplicons are produced under
      identical polymerase chain reaction (PCR) conditions with individual separate
      amplification of exon 2 and exon 3 of the haplotypic alleles in most heterozygous
      combinations. Time- and money-saving one-directional Big Dye Terminator cycle
      sequencing is shown to provide reliable high resolution typing of the HLA-A
      alleles, even in a few cases of two amplicons in one primer reaction mixture. In
      comparison, to other sequencing-based typing (SBT) techniques the applied typing
      strategy minimizes the risk of unequal amplification or of drop-outs of one of
      the haplotypic alleles and allows unequivocal definition of the cis/ trans
      linkage of polymorphic positions of the complete exon 2 and exon 3 in most
      heterozygous cells. This also includes detection of new alleles differing in the
      polymorphic template generating primer annealing sites as well as in unusual
      combinations of known exon 2 and 3 sequences. With 10 primer sets working under
      identical conditions for pre-grouping and separate amplification of the
      haplotypic alleles our SBT procedure also could be implemented in clinical
      settings of large-scale stem cell donor histocompatibility testing for fast
      molecular HLA-A matching.

PMID- 10082435
TI  - HLA-DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients.
AB  - In Sardinia, like in other Caucasoid populations, rheumatoid arthritis (RA) is
      significantly associated with HLA-DR4 and DR1 antigens. To discover which DR4 and
      DR1 alleles were associated with the disease we selected 22 Sardinian patients
      affected by RA. Fifty DR4+ and 28 DR1+ healthy individuals coming from the same
      geographical area were used as controls. In the Sardinian patients only two
      DRB1*04 alleles were observed: DRB1*0405 in 11 and DRB1*0403 in three patients.
      The DRB1*0102 allele was observed in two patients and DRB1*0101 in six patients.
      Hereditary predisposition to RA in Sardinia therefore seems to be almost
      exclusively associated with the DRB1*0405 and DRB1*0101 alleles which share the
      67LLEQRRAA74-85VG86 epitope in the peptide binding groove.

PMID- 10082436
TI  - Impaired binding of a DQ2 and DQ8-binding HSV VP16 peptide to a
      DQA1*0501/DQB1*0302 trans class II heterodimer.
AB  - DQalpha and DQbeta trans heterodimeric HLA-DQ molecules form in individuals
      heterozygous for the DQ2 and DQ8 specificities. Unique functions and disease
      associations have been postulated for such trans-dimers, which may be different
      from cis-encoded DQ molecules encoded by the corresponding haplotypes. We
      analyzed the ability of the trans-dimer encoded by HLA-DQA1*0501/DQB1*0302 to
      bind a peptide antigen which interacts with DQ molecules encoded by both parental
      haplotypes. Markedly impaired binding was observed, consistent with both the use
      of different anchor residues and with changes in levels of DQ cis-dimer
      availability for peptide binding interactions.

PMID- 10082437
TI  - CTLA4 promoter and exon 1 dimorphisms in multiple sclerosis.
AB  - The human cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene may be a
      candidate susceptibility gene in multiple sclerosis (MS). In this study the
      distribution of the dimorphisms of exon 1 (+49 A/G) and promoter (-318 C/T)
      regions of the CTLA4 gene was analysed in 296 unrelated Norwegian MS patients and
      271 matched controls by polymerase chain reaction and restriction fragment length
      polymorphism. The frequency of the exon 1 (+49) A-G genotype was increased in
      patients (57%) compared with controls (44%) (Pcorrected=0.01), and even more
      increased in patients with relapsing remitting MS (59%) (Pcorrected=0.006). No
      other significant differences were found between clinical subgroups of patients
      or between HLA-DRB1*1501, DQB1*0602-positive and negative patients and controls.

PMID- 10082438
TI  - Neoral: the microemulsion formulation.

PMID- 10082439
TI  - Current status of diagnosis of small bowel rejection.

PMID- 10082440
TI  - Pediatric kidney transplantation utilizing living unrelated donors: anecdote or
      solution to the kidney shortage?

PMID- 10082441
TI  - Immunomodulatory actions of intravenous immunoglobulin (IVIG): potential
      applications in solid organ transplant recipients.
AB  - Intravenous gammaglobulin (IVIG) products are known to have powerful
      immunomodulatory and anti-inflammatory functions in vitro and in vivo. In
      addition, IVIG has shown benefit in the treatment of many human autoimmune and
      inflammatory disorders. One potential mechanism of action responsible for these
      beneficial effects is the down-regulation of deleterious autoantibody titers
      through idiotypic-anti-idiotypic networks. Until recently, few data were
      available on the use of IVIG in the management of alloimmune disorders. In this
      review, we will discuss current data on the use of pooled human gammaglobulin as
      an agent with potential to regulate undesirable alloimmune responses and
      allosensitization through similar idiotypic-anti-idiotypic circuits and how this
      therapy could be of benefit in the management of highly sensitized patients both
      pre- and post-transplant. We will also discuss other potential anti-inflammatory
      and immunoregulatory mechanisms induced by IVIG treatment and how these may be
      applied to improve transplantability and outcomes in human transplantation.

PMID- 10082442
TI  - Indications for pediatric liver transplantation.
AB  - This review discusses the indications for orthotopic liver transplantation (OLT)
      in children and provides guidelines for the appropriate time to list children for
      transplant. The diseases for which OLT are indicated in children are divided into
      diagnostic categories with a focus on the natural history and appropriate medical
      and surgical therapy prior to transplantation. Contraindications to
      transplantation pertinent to specific diseases are outlined, with particular
      emphasis on complex metabolic defects with extrahepatic manifestations. The
      clinical conditions which indicate that listing for OLT is appropriate, as well
      as the relative and absolute contraindications, irrespective of diagnosis, are
      discussed. The importance of malnutrition and poor development as listing
      criteria is stressed. Special timing considerations for diagnoses relevant to the
      pediatric age group, e.g. urea cycle defects and Crigler-Najjar syndrome, are
      emphasized. Finally, the impact of co-existing extrahepatic disease on the
      decision to list children for OLT is reviewed.

PMID- 10082443
TI  - Pediatric renal transplantation: indications and special considerations. A
      position paper from the Pediatric Committee of the American Society of Transplant
      Physicians.
AB  - Renal transplantation of children with chronic renal insufficiency (CRI) and end
      stage renal disease (ESRD) appears to be the optimal form of renal replacement
      therapy. This report, which expresses the opinions of the nephrology members of
      the Pediatric Committee of the American Society of Transplant Physicians,
      discusses the indications for pediatric renal transplantation and identifies the
      unique aspects of caring for children with CRI and ESRD. Indications for
      pediatric renal transplantation include: 1) symptoms of uremia not responsive to
      standard therapy; 2) failure to thrive due to limitations in total caloric
      intake; 3) delayed psychomotor development; 4) hypervolemia; 5) hyperkalemia; and
      6) metabolic bone disease due to renal osteodystrophy. The urgency and timing of
      renal transplantation in children must be considered in the context of a number
      of issues unique to children with CRI and ESRD such as delayed cognitive and
      educational performance, growth retardation, delayed puberty, etiology of ESRD,
      and timing of immunizations. In addition, these children frequently display
      various inherited and sporadic syndromes with multiorgan involvement requiring
      the expertise of a variety of pediatric subspecialists including the pediatric
      urologist, who plays a critical role in the evaluation of children with
      obstructive uropathy and other anomalies of the genito-urinary system. The
      advantages of a living-related donor are also delineated. The importance of
      adequate immunosuppression on graft function, early recognition of the signs and
      symptoms acute rejection, preventive strategies for minimizing the morbidity and
      mortality from viral infections in the post-transplant period, and the impact of
      transplantation on cognitive function, educational status, and catch-up growth
      are also discussed. To address these complex issues, transplant care of pediatric
      patients must be provided by a multidisciplinary team of pediatric health care
      professionals.

PMID- 10082444
TI  - Renal transplantation in children with sickle cell disease: a report of the North
      American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Sickle cell disease is a rare cause of end-stage renal disease (ES-RD) in
      pediatrics accounting for only 0.5% and 0.2% of the patients registered in the
      dialysis and transplant arms of the NAPRTCS database, respectively. Accordingly,
      the single-center experience with this disorder is extremely rare, and little
      information on patient and graft outcome is available. Between 1989-1995, 9
      patients with sickle cell nephropathy (5 male and 4 female) received 10
      transplants [7 cadaver (CAD) and 3 living-related donor (LRD)]. The mean age at
      the time of the first transplant was 16.0 +/- 1.6 years. Prior to
      transplantation, all patients received maintenance dialysis (4 HD, 4 PD, 1 HD/PD)
      for 21.4 +/- 16.1 months (range 3-47 months), and all had received > 5 lifetime
      random blood transfusions. There was a mean 15.9 consecutive days of
      hospitalization from transplantation to discharge. Initial immunosuppression
      consisted of methyl predinsolone/prednisone (9 patients) cyclosporine (7
      patients) and azathioprine (8 patients). ATG/ALG or OKT3 were used in 3 CAD
      transplants. There have been 21 acute rejection episodes in 7 of the 9 patients.
      Two patients had no rejections and 2 patients had 6 rejections each. Six of the
      21 rejection episodes occurred within the first 100 days post-transplant. Nine
      (43%) of the rejections were completely reversed, the reversal rate varying from
      71% for first rejections to 29% for second and subsequent rejections. Four (40%)
      of the 10 grafts have failed. Graft survival at 12 and 24 months post-transplant
      is 0.89 +/- 0.11 and 0.71 +/- 0.18, respectively. Patient survival is 89%. The
      present experience suggests that renal transplantation is a viable option for the
      adolescent patient with sickle cell nephropathy and ESRD.

PMID- 10082445
TI  - Correlation of mucosal disaccharidase activities with histology in evaluation of
      rejection following intestinal transplantation.
AB  - Following intestinal transplantation, we have found that recovery from severe
      rejection may be difficult to identify. In this study we sought to ascertain
      whether concurrent determination of mucosal disaccharidase activities and
      histologic assessment improves the accuracy of diagnosis of rejection. Histologic
      changes were graded blindly using a standard set of diagnostic criteria, and
      these changes were compared over time to maltase, sucrase, lactase, and
      palatinase activities in four pediatric patients under treatment for severe
      rejection. The histologic criteria, which included magnitude of enterocyte loss,
      degree of granulation tissue, severity of villus atrophy, and frequency of
      apoptosis and cryptitis, were found to correlate with one another over time
      irrespective of outcome (r = 0.72 to r = 0.85). Enzyme activities were also
      correlated with each other over time (r = 0.64 to r = 0.80). However, the
      correlation between histologic diagnosis and enzyme activity was weaker (r = 
      0.48 to r = -0.57). Furthermore, neither histologic nor enzyme evaluation early
      in the course of rejection predicted ultimate clinical outcome. The results of
      this investigation show that determination of mucosal disaccharidase activity
      provides no additional useful information concerning efficacy of anti-rejection
      therapy as compared to histologic analysis alone.

PMID- 10082446
TI  - Living-unrelated renal transplantation in children: a report of the North
      American Pediatric Renal Transplant Cooperative Study (NAPRTCS)
AB  - The shortage of cadaver kidneys available for organ donation compared to growing
      demand has led to an increase in the use of living-unrelated donors (LURD) for
      renal transplantation (Tx). Results from trials in adults show that 1-year graft
      survival rates in LURD are similar to living-related donor (LRD) rates and
      superior to those of cadaver renal donor (CAD) transplants. We report our
      experience with 38 LURD transplants for children enrolled in NAPRTCS that were
      performed between 1987 and 1997. Ages of recipients at Tx were 0-5 years (n=8), 6
      12 (n=10), and >12 years (n=20). Twenty nine were primary Tx, seven were second
      Tx, and two were third Tx. HLA antigen data showed that the number of 2-antigen
      mismatches for each locus was 44.7% for HLA-A, 71.1% for HLA-B, and 55.3% for HLA
      DR. There were 7 donor/recipient pairs with a 6-antigen mismatch, 12 pairs with a
      5-antigen mismatch, while there were 6 pairs with a 3-antigen match of which 3
      pairs had at least one match at each of the A, B, and DR loci. A total of 38
      acute rejection episodes occurred in 25 LURD recipients. Among primary grafts the
      incidence of first acute rejection at 30 d post-Tx was 46% in LURD vs. 29% in LRD
      and 37% in CAD recipients; at 1 year post-Tx it was 76% in LURD vs. 48% in LRD
      and 62% in CAD recipients. Acute tubular necrosis (ATN) was reported in four or
      10.5% of LURD transplants compared with 5.4% in LRD and 19.0% in CAD recipients.
      There were 12 LURD graft failures, due to vascular thrombosis (3), acute
      rejection (2), recurrence of original disease (1), infection (3), and patient
      death (3). Estimated primary graft survival probabilities (+/- SE) at 12 months
      post-Tx are 0.825 +/- 0.071 for LURD, compared to 0.911 +/- 0.006 for LRD, and
      0.815 +/- 0.009 for CAD. We conclude that data from this study show that LURD Tx
      in children have a low rate of ATN that is similar to that of LRD Tx. However,
      LURD Tx have a high incidence of acute rejection, and the graft survival at 12
      and 24 months post-Tx is inferior to LRD Tx. There is a high frequency of graft
      loss due to causes other than rejection, and these may be related to adverse
      recipient selection criteria.

PMID- 10082447
TI  - Bioavailability of two oral formulations of cyclosporin A in uremic children
      before renal transplantation.
AB  - The bioavailability of two oral formulations of cyclosporin A (Sandimmun and
      Neoral) was assessed in 10 children with end-stage renal disease (ESRD), while at
      a steady state on a dialytic procedure. The study was performed according to a
      randomized, double blind, cross-over design, allowing a 1-month washout period
      between studies. Each patient received 2.5 mg/microg of oral cyclosporin A every
      12 h, either Sandimmun (SAN) or Neoral (NEO). Serum concentrations of cyclosporin
      A were determined serially during a 24 h period, after the 5th dose of
      cylosporin. Serum concentrations against time curves were constructed and
      bioavailability of both medications, expressed as AUC and Cmax, were compared. A
      statistically significant increase was observed in the AUC and Cmax of NEO, which
      were 90% and 130% higher, respectively, than those of SAN. Considering that the
      internationally accepted criteria for bioequivalence allows a 20% variation in
      AUC and Cmax, it appears that Neoral and Sandimmun do not bear bioequivalence in
      children with ESRD. Notwithstanding, there were no significant differences in
      trough levels between both formulations. We conclude that, if trough levels are
      the only source of information for dosing design, Neoral could be substituted for
      Sandimmun on a 1:1 basis. However, a 1:1 drug substitution is not suitable when
      AUC is used in children with ESRD.

PMID- 10082448
TI  - Engraftment and chimerism, particularly of T- and B-cells, in children undergoing
      allogeneic bone marrow transplantation.
AB  - The spectrum of pediatric bone marrow transplantation has changed in recent
      years. Mismatched and unrelated donor transplants are common, demanding an
      increased vigilance to detect incipient graft failure, secondary lymphoma as well
      as relapse and other problems, which now are potentially treatable. To diagnose
      these complications it may be important to know whether blood and marrow cells
      are of recipient or donor origin. To evaluate the role of mixed donor-recipient
      chimerism in relation to clinical problems we adapted a polymerase chain-reaction
      technique, using fluorescent primers analyzing DNA fragment length polymorphisms,
      to follow prospectively 17 bone marrow grafted children. To increase the
      precision of chimerism analysis, immunomagnetically isolated leukocyte
      populations were assayed in selected cases. Five patients encountered clinical
      problems related to chimerism. One infant with adenosine deaminase deficiency
      failed to engraft stem cells, yet succumbed to graft-versus-host disease,
      mediated by mature donor T-cells. Three children developed significant mixed
      chimerism. One of these three patients died in relapse of leukemia, while the two
      other patients who had received T-cell depleted grafts had persistent recipient T
      cells, in spite of engraftment. After 5 months, these were displaced by donor T
      cells in one of the patients. In the fifth patient, also after T-cell depleted
      BMT, a fatal donor cell lymphoma occurred. Twelve children had stable full
      chimerism or in one case a low grade mixed chimerism and remain disease-free
      throughout follow up (median 9 months). In conclusion, the analysis of chimerism,
      particularly of separated leukocyte populations, offers an almost indispensable
      insight and a basis for therapeutic decisions in complicated situations such as
      grafting involving unrelated or mismatched donors, graft manipulation, adoptive
      immunotherapy and in immunodeficiency patients.

PMID- 10082449
TI  - Use of disodium pamidronate in children with hypercalcemia awaiting liver
      transplantation.
AB  - We report four children with advanced liver disease awaiting liver
      transplantation who developed moderately severe hypercalcemia (range: 1.65-2.40
      mmol/L) while receiving total parenteral nutrition. Hypercalcemia had been
      unresponsive to cessation of calcium intake and therapy with loop diuretics and
      calcitonin. One or two intravenous doses of disodium pamidronate (35-50 mg/m2)
      resulted in normalization of plasma calcium concentration within 2-4 d in all
      four children. Pamidronate may be useful for children with hypercalcemia
      associated with liver disease.

PMID- 10082450
TI  - Mobilization of peripheral blood progenitor cells using 16 versus 10 mg/kg/d G
      CSF in children with malignancies.
AB  - Administration of hematopoietic growth factors, with or without chemotherapy, can
      augment progenitor cell numbers available for collection. The dose of granulocyte
      colony stimulating factor (G-CSF) used for mobilization of peripheral blood
      progenitor cells (PBPC) is controversial, and doses between 5 and 32 microg/kg/d
      have been reported in adults. In order to determine the dose-response effect for
      G-CSF in mobilizing PBPC in children, we randomized 30 children with malignancies
      to receive either 16 or 10 microg/kg/d subcutaneously starting on the day after
      the disease-oriented chemotherapy regimen and continuing until the completion of
      leukapheresis. Leukapheresis commenced after threshold WBC > 1 x 10(9)/L was
      achieved and continued until 10 x 10(6) CD34+ cells/kg were obtained or for 6
      procedures. Both treatment groups achieved an adequate yield of CD34+ cells with
      an average of 4 leukapheresis procedures. The numbers of CD34+ cells/kg were 8.3
      x 10(6) and 11.7 x 10(6) in patients receiving 16 and 10 microg/kg/d doses of G
      CSF, respectively, or 2.1 x 10(6) and 3.7 x 10(6) cells/kg per leukapheresis. The
      levels of CD34+ cells in peripheral blood had a wide interindividual variation,
      and were not significantly different after 16 or 10 microg/kg doses of daily G
      CSF. We conclude that there is no advantage to using 16 microg/kg/d of G-CSF post
      chemotherapy for PBPC mobilization in children.

PMID- 10082451
TI  - Pediatric Transplant Grand Rounds. Pediatric kidney transplantation at Stanford.
AB  - (1) We believe that we have achieved excellent graft survival with pediatric
      kidney transplantation because: (a) we have had no technical losses; (b) there
      have been no primary immunologic losses within 4 years following transplantation;
      (c) we have avoided ATN. (2) Our cyclosporine dosage has been greater than the
      average dosage reported by the NAPRTCS, and we believe that this has led to: (a)
      a low incidence of rejection episodes; (b) because of this, good 1 and 2 year
      average serum creatinine levels. (3) In the management of adult-sized kidneys in
      infants and small children I have discussed: (a) the rationale and strategy to
      prevent vascular thrombosis, ATN and primary non-function; (b) the importance of
      optimizing intravascular volume, as well as renal and aortic blood flow. (4) With
      regard to the management of congenital urologic abnormalities I have discussed:
      (a) the strategy to avoid unnecessary surgery and to avoid scar around the aorta
      and the vena cava, particularly in infants and small children; (b) my philosophy
      regarding the abnormal bladder and the successful use of the small
      defunctionalized urinary bladder. We believe that these have been the primary
      ingredients to the success we have seen. I also harken back and continue to
      practice the adage advanced by my former mentor Dr. Fred Belzer that 'no kidney
      is better than a bad kidney!' And this could not be more true than in pediatric
      kidney transplantation, where graft failure enhanced by suboptimal graft quality
      may potentially both cripple the child and shorten his/her life.

PMID- 10082452
TI  - Comment on 'The effect of rhGH in vitro on donor-specific hyporesponsiveness in
      pediatric transplantation.

PMID- 10082453
TI  - The origin of chaos in the outer solar system 
AB  - Classical analytic theories of the solar system indicate that it is stable, but
      numerical integrations suggest that it is chaotic. This disagreement is resolved
      by a new analytic theory. The theory shows that the chaos among the jovian
      planets results from the overlap of the components of a mean motion resonance
      among Jupiter, Saturn, and Uranus, and provides rough estimates of the Lyapunov
      time (10(7) years) and the dynamical lifetime of Uranus (10(18) years). The
      jovian planets must have entered the resonance after all the gas and most of the
      planetesimals in the protoplanetary disk were removed.

PMID- 10082454
TI  - Compositional stratification in the deep mantle 
AB  - A boundary between compositionally distinct regions at a depth of about 1600
      kilometers may explain the seismological observations pertaining to Earth's lower
      mantle, produce the isotopic signatures of mid-ocean ridge basalts and oceanic
      island basalts, and reconcile the discrepancy between the observed heat flux and
      the heat production of the mid-ocean ridge basalt source region. Numerical models
      of thermochemical convection imply that a layer of material that is intrinsically
      about 4 percent more dense than the overlying mantle is dynamically stable.
      Because the deep layer is hot, its net density is only slightly greater than
      adiabatic and its surface develops substantial topography.

PMID- 10082455
TI  - Compositional heterogeneity in the bottom 1000 kilometers of Earth's mantle:
      toward a hybrid convection model 
AB  - Tomographic imaging indicates that slabs of subducted lithosphere can sink deep
      into Earth's lower mantle. The view that convective flow is stratified at 660
      kilometer depth and preserves a relatively pristine lower mantle is therefore not
      tenable. However, a range of geophysical evidence indicates that compositionally
      distinct, hence convectively isolated, mantle domains may exist in the bottom
      1000 kilometers of the mantle. Survival of these domains, which are perhaps
      related to local iron enrichment and silicate-to-oxide transformations, implies
      that mantle convection is more complex than envisaged by conventional end-member
      flow models.

PMID- 10082456
TI  - Dipping low-velocity layer in the mid-lower mantle: evidence for geochemical
      heterogeneity 
AB  - Data from western United States short-period seismic networks reveal a conversion
      from an S to a P wave within a low seismic velocity layer (greater than or equal
      to the 4 percent velocity difference compared to the surrounding mantle) in the
      mid-lower mantle (1400 to 1600 kilometers deep) east of the Mariana and Izu-Bonin
      subduction zones. The low-velocity layer (about 8 kilometers thick) dips 30
      degrees to 40 degrees southward and is at least 500 kilometers by 300 kilometers.
      Its steep dip, large velocity contrast, and sharpness imply a chemical rather
      than a thermal origin. Ancient oceanic crust subducted into the lower mantle is a
      plausible candidate for the low-velocity layer because of its broad thin extent.

PMID- 10082457
TI  - Chemical transformations in individual ultrasmall biomimetic containers.
AB  - Individual phospholipid vesicles, 1 to 5 micrometers in diameter, containing a
      single reagent or a complete reaction system, were immobilized with an infrared
      laser optical trap or by adhesion to modified borosilicate glass surfaces.
      Chemical transformations were initiated either by electroporation or by
      electrofusion, in each case through application of a short (10-microsecond),
      intense (20 to 50 kilovolts per centimeter) electric pulse delivered across
      ultramicroelectrodes. Product formation was monitored by far-field laser
      fluorescence microscopy. The ultrasmall characteristic of this reaction volume
      led to rapid diffusional mixing that permits the study of fast chemical kinetics.
      This technique is also well suited for the study of reaction dynamics of
      biological molecules within lipid-enclosed nanoenvironments that mimic cell
      membranes.

PMID- 10082458
TI  - Nonequilibrium self-assembly of long chains of polar molecules in superfluid
      helium 
AB  - It is shown that in the low-temperature (0.37 kelvin) environment of superfluid
      helium droplets, long-range dipole-dipole forces acting between two polar
      molecules can result in the self-assembly of noncovalently bonded linear chains.
      At this temperature the effective range of these forces is on the nanometer
      scale, making them important in the growth of nanoscale structures. In
      particular, the self-assembly of exclusively linear hydrogen cyanide chains is
      observed, even when the folded structures are energetically favored. This
      suggests a design strategy for the growth of new nanoscale oligomers composed of
      monomers with defined dipole (or higher order) moment directions.

PMID- 10082459
TI  - Epitaxial cubic gadolinium oxide as a dielectric for gallium arsenide passivation
AB  - Epitaxial growth of single-crystal gadolinium oxide dielectric thin films on
      gallium arsenide is reported. The gadolinium oxide film has a cubic structure
      isomorphic to manganese oxide and is (110)-oriented in single domain on the (100)
      gallium arsenide surface. The gadolinium oxide film has a dielectric constant of
      approximately 10, with low leakage current densities of about 10(-9) to 10(-10)
      amperes per square centimeter at zero bias. Typical breakdown field is 4
      megavolts per centimeter for an oxide film 185 angstroms thick and 10 megavolts
      per centimeter for an oxide 45 angstroms thick. Both accumulation and inversion
      layers were observed in the gadolinium oxide-gallium arsenide metal oxide
      semiconductor diodes, using capacitance-voltage measurements. The ability to grow
      thin single-crystal oxide films on gallium arsenide with a low interfacial
      density of states has great potential impact on the electronic industry of
      compound semiconductors.

PMID- 10082460
TI  - Degradation mechanism of small molecule-based organic light-emitting devices 
AB  - Studies on the long-term degradation of organic light-emitting devices (OLEDs)
      based on tris(8-hydroxyquinoline) aluminum (AlQ3), the most widely used
      electroluminescent molecule, reveal that injection of holes in AlQ3 is the main
      cause of device degradation. The transport of holes into AlQ3 caused a decrease
      in its fluorescence quantum efficiency, thus showing that cationic AlQ3 species
      are unstable and that their degradation products are fluorescence quenchers.
      These findings explain the success of different approaches to stabilizing OLEDs,
      such as doping of the hole transport layer, introducing a buffer layer at the
      hole-injecting contact, and using mixed emitting layers of hole and electron
      transporting molecules.

PMID- 10082461
TI  - Phase-separated composite films for liquid crystal displays 
AB  - A method of preparing liquid crystal devices by phase separation of liquid
      crystal from its solution in a prepolymer, which results in adjacent layers of
      liquid crystal and polymer, is described. Liquid crystals in these phase
      separated composite films exhibit electro-optical properties not observed in
      devices prepared by conventional methods, polymer dispersion, or polymer
      stabilization methods. Devices incorporating ferroelectric liquid crystals have
      gray scale and switch 100 times faster at low fields than conventional surface
      stabilized devices. This method makes it possible to prepare devices with liquid
      crystal film thickness comparable to optical wavelengths.

PMID- 10082462
TI  - An adiabatic quantum electron pump 
AB  - A quantum pumping mechanism that produces dc current or voltage in response to a
      cyclic deformation of the confining potential in an open quantum dot is reported.
      The voltage produced at zero current bias is sinusoidal in the phase difference
      between the two ac voltages deforming the potential and shows random fluctuations
      in amplitude and direction with small changes in external parameters such as
      magnetic field. The amplitude of the pumping response increases linearly with the
      frequency of the deformation. Dependencies of pumping on the strength of the
      deformations, temperature, and breaking of time-reversal symmetry were also
      investigated.

PMID- 10082463
TI  - Structural maturation of neural pathways in children and adolescents: in vivo
      study.
AB  - Structural maturation of fiber tracts in the human brain, including an increase
      in the diameter and myelination of axons, may play a role in cognitive
      development during childhood and adolescence. A computational analysis of
      structural magnetic resonance images obtained in 111 children and adolescents
      revealed age-related increases in white matter density in fiber tracts
      constituting putative corticospinal and frontotemporal pathways. The maturation
      of the corticospinal tract was bilateral, whereas that of the frontotemporal
      pathway was found predominantly in the left (speech-dominant) hemisphere. These
      findings provide evidence for a gradual maturation, during late childhood and
      adolescence, of fiber pathways presumably supporting motor and speech functions.

PMID- 10082464
TI  - Signaling of cell fate decisions by CLAVATA3 in Arabidopsis shoot meristems.
AB  - In higher plants, organogenesis occurs continuously from self-renewing apical
      meristems. Arabidopsis thaliana plants with loss-of-function mutations in the
      CLAVATA (CLV1, 2, and 3) genes have enlarged meristems and generate extra floral
      organs. Genetic analysis indicates that CLV1, which encodes a receptor kinase,
      acts with CLV3 to control the balance between meristem cell proliferation and
      differentiation. CLV3 encodes a small, predicted extracellular protein. CLV3 acts
      nonautonomously in meristems and is expressed at the meristem surface overlying
      the CLV1 domain. These proteins may act as a ligand-receptor pair in a signal
      transduction pathway, coordinating growth between adjacent meristematic regions.

PMID- 10082465
TI  - Acoel flatworms: earliest extant bilaterian Metazoans, not members of
      Platyhelminthes.
AB  - Because of their simple organization the Acoela have been considered to be either
      primitive bilaterians or descendants of coelomates through secondary loss of
      derived features. Sequence data of 18S ribosomal DNA genes from non-fast evolving
      species of acoels and other metazoans reveal that this group does not belong to
      the Platyhelminthes but represents the extant members of the earliest divergent
      Bilateria, an interpretation that is supported by recent studies on the embryonic
      cleavage pattern and nervous system of acoels. This study has implications for
      understanding the evolution of major body plans, and for perceptions of the
      Cambrian evolutionary explosion.

PMID- 10082466
TI  - Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic
      activity.
AB  - Activity shapes the structure of neurons and their circuits. Two-photon imaging
      of CA1 neurons expressing enhanced green fluorescent protein in developing
      hippocampal slices from rat brains was used to characterize dendritic
      morphogenesis in response to synaptic activity. High-frequency focal synaptic
      stimulation induced a period (longer than 30 minutes) of enhanced growth of small
      filopodia-like protrusions (typically less than 5 micrometers long). Synaptically
      evoked growth was long-lasting and localized to dendritic regions close (less
      than 50 micrometers) to the stimulating electrode and was prevented by blockade
      of N-methyl-D-aspartate receptors. Thus, synaptic activation can produce rapid
      input-specific changes in dendritic structure. Such persistent structural changes
      could contribute to the development of neural circuitry.

PMID- 10082467
TI  - Variability in spike trains during constant and dynamic stimulation.
AB  - In a recent study, it was concluded that natural time-varying stimuli are
      represented more reliably in the brain than constant stimuli are. The results
      presented here disagree with this conclusion, although they were obtained from
      the same identified neuron (H1) in the fly's visual system. For large parts of
      the neuron's activity range, the variability of the responses was very similar
      for constant and time-varying stimuli and was considerably smaller than that in
      many visual interneurons of vertebrates.

PMID- 10082468
TI  - The role of local actin instability in axon formation.
AB  - The role of localized instability of the actin network in specifying axonal fate
      was examined with the use of rat hippocampal neurons in culture. During normal
      neuronal development, actin dynamics and instability polarized to a single growth
      cone before axon formation. Consistently, global application of actin
      depolymerizing drugs and of the Rho-signaling inactivator toxin B to nonpolarized
      cells produced neurons with multiple axons. Moreover, disruption of the actin
      network in one individual growth cone induced its neurite to become the axon.
      Thus, local instability of the actin network restricted to a single growth cone
      is a physiological signal specifying neuronal polarization.

PMID- 10082469
TI  - Reversible conversion of monomeric human prion protein between native and
      fibrilogenic conformations.
AB  - Prion propagation involves the conversion of cellular prion protein (PrPC) into a
      disease-specific isomer, PrPSc, shifting from a predominantly alpha-helical to
      beta-sheet structure. Here, conditions were established in which recombinant
      human PrP could switch between the native alpha conformation, characteristic of
      PrPC, and a compact, highly soluble, monomeric form rich in beta structure. The
      soluble beta form (beta-PrP) exhibited partial resistance to proteinase K
      digestion, characteristic of PrPSc, and was a direct precursor of fibrillar
      structures closely similar to those isolated from diseased brains. The conversion
      of PrPC to beta-PrP in suitable cellular compartments, and its subsequent
      stabilization by intermolecular association, provide a molecular mechanism for
      prion propagation.

PMID- 10082470
TI  - Activation of receptor for advanced glycation end products: a mechanism for
      chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis.
AB  - Receptor for advanced glycation end products (RAGE) is a member of the
      immunoglobulin superfamily of cell surface molecules and engages diverse ligands
      relevant to distinct pathological processes. One class of RAGE ligands includes
      glycoxidation products, termed advanced glycation end products, which occur in
      diabetes, at sites of oxidant stress in tissues, and in renal failure and
      amyloidoses. RAGE also functions as a signal transduction receptor for amyloid
      beta peptide, known to accumulate in Alzheimer disease in both affected brain
      parenchyma and cerebral vasculature. Interaction of RAGE with these ligands
      enhances receptor expression and initiates a positive feedback loop whereby
      receptor occupancy triggers increased RAGE expression, thereby perpetuating
      another wave of cellular activation. Sustained expression of RAGE by critical
      target cells, including endothelium, smooth muscle cells, mononuclear phagocytes,
      and neurons, in proximity to these ligands, sets the stage for chronic cellular
      activation and tissue damage. In a model of accelerated atherosclerosis
      associated with diabetes in genetically manipulated mice, blockade of cell
      surface RAGE by infusion of a soluble, truncated form of the receptor completely
      suppressed enhanced formation of vascular lesions. Amelioration of
      atherosclerosis in these diabetic/atherosclerotic animals by soluble RAGE
      occurred in the absence of changes in plasma lipids or glycemia, emphasizing the
      contribution of a lipid- and glycemia-independent mechanism(s) to atherogenesis,
      which we postulate to be interaction of RAGE with its ligands. Future studies
      using mice in which RAGE expression has been genetically manipulated and with
      selective low molecular weight RAGE inhibitors will be required to definitively
      assign a critical role for RAGE activation in diabetic vasculopathy. However,
      sustained receptor expression in a microenvironment with a plethora of ligand
      makes possible prolonged receptor stimulation, suggesting that interaction of
      cellular RAGE with its ligands could be a factor contributing to a range of
      important chronic disorders.

PMID- 10082471
TI  - TIMP-4 is regulated by vascular injury in rats.
AB  - The role of basement membrane-degrading matrix metalloproteinases (MMPs) in
      enabling vascular smooth muscle cell migration after vascular injury has been
      established in several animal models. In contrast, the role of their native
      inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), has
      remained unproven despite frequent coregulation of MMPs and TIMPs in other
      disease states. We have investigated the time course of expression and
      localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days,
      and 14 days after balloon injury by in situ hybridization, immunohistochemistry,
      and Western blot analysis. TIMP-4 protein was present in the adventitia of
      injured carotid arteries from 24 hours after injury. At 7 and 14 days after
      injury, widespread immunostaining for TIMP-4 was observed throughout the
      neointima, media, and adventitia of injured arteries. Western blot analysis
      confirmed the quantitative increase in TIMP-4 protein at 7 and 14 days. In situ
      hybridization detected increased expression of TIMP-4 as early as 24 hours after
      injury and a marked induction in neointimal cells 7 days after injury. We then
      studied the effect of TIMP-4 protein on the migration of smooth muscle cells
      through a matrix-coated membrane in vitro and demonstrated a 53% reduction in
      invasion of rat vascular smooth muscle cells. These data and the temporal
      relationship between the upregulation of TIMP-4, its accumulation, and the onset
      of collagen deposition suggest an important role for TIMP-4 in the proteolytic
      balance of the vasculature controlling both smooth muscle migration and collagen
      accumulation in the injured arterial wall.

PMID- 10082472
TI  - Mitogen-activated protein/extracellular signal-regulated kinase inhibition
      attenuates angiotensin II-mediated signaling and contraction in spontaneously
      hypertensive rat vascular smooth muscle cells.
AB  - This study investigates the role of extracellular signal-regulated kinases (ERKs)
      in angiotensin II (Ang II)-generated intracellular second messengers (cytosolic
      free Ca2+ concentration, ie, [Ca2+]i, and pHi) and in contraction in isolated
      vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR)
      and control Wistar Kyoto rats (WKY) using the selective mitogen-activated protein
      (MAP)/ERK inhibitor, PD98059. VSMCs from mesenteric arteries were cultured on
      Matrigel basement membrane matrix. These cells, which exhibit a contractile
      phenotype, were used to measure [Ca2+]i, pHi, and contractile responses to Ang II
      (10(-12) to 10(-6) mol/L) in the absence and presence of PD98059 (10(-5) mol/L).
      [Ca2+]i and pHi were measured by fura-2 and BCECF methodology, respectively, and
      contraction was determined by photomicroscopy. Ang II-stimulated ERK activity was
      measured by Western blot analysis using a phospho-specific ERK-1/ERK-2 antibody
      and by an MAPK enzyme assay. Ang II increased [Ca2+]i and pHi and contracted
      cells in a dose-dependent manner. Maximum Ang II-elicited contraction was greater
      (P<0.05) in SHR (41.9+/-5.1% reduction in cell length relative to basal length)
      than in WKY (28.1+/-3.0% reduction in cell length relative to basal length).
      Basal [Ca2+]i, but not basal pHi, was higher in SHR compared with WKY. [Ca2+]i
      and pHi effects of Ang II were enhanced (P<0.05) in SHR compared with WKY
      (maximum Ang II-induced response [Emax] of [Ca2+]i, 576+/-24 versus 413+/-43
      nmol/L; Emax of pHi, 7.33+/-0.01 versus 7.27+/-0.03, SHR versus WKY). PD98059
      decreased the magnitude of contraction and attenuated the augmented Ang II
      elicited contractile responses in SHR (Emax,19. 3+/-3% reduction in cell length
      relative to basal length). Ang II-stimulated [Ca2+]i (Emax, 294+/-55 nmol/L) and
      pHi (Emax, 7. 27+/-0.04) effects were significantly reduced by PD98059 in SHR.
      Ang II-induced ERK activity was significantly greater (P<0.05) in SHR than in
      WKY. In conclusion, Ang II-stimulated signal transduction and associated VSMC
      contraction are enhanced in SHR. MAP/ERK inhibition abrogated sustained
      contraction and normalized Ang II effects in SHR. These data suggest that ERK
      dependent signaling pathways influence contraction and that they play a role in
      vascular hyperresponsiveness in SHR.

PMID- 10082473
TI  - Molecular mechanisms of neutrophil-endothelial cell adhesion induced by redox
      imbalance.
AB  - Previous studies have implicated a role for intracellular thiols in the
      activation of nuclear factor-kappaB and transcriptional regulation of endothelial
      cell adhesion molecules. This study was designed to determine whether changes in
      endothelial cell glutathione (GSH) or oxidized glutathione (GSSG) can alter
      neutrophil adhesivity and to define the molecular mechanism that underlies this
      GSSG/GSH-induced adhesion response. Treatment of human umbilical vein endothelial
      cell (HUVEC) monolayers for 6 hours with 0.2 mmol/L diamide and 1 mmol/L
      buthionine sulfoximine (BSO) decreased GSH levels and increased the ratio of GSSG
      to GSH without cell toxicity. These redox changes are similar to those observed
      with anoxia/reoxygenation. Diamide plus BSO-induced thiol/disulfide imbalance was
      associated with a biphasic increase in neutrophil adhesion to HUVECs with peak
      responses observed at 15 minutes (phase 1) and 240 minutes (phase 2). N
      Acetylcysteine treatment attenuated neutrophil adhesion in both phases, which
      indicated a role for GSH in the adhesion responses. Interestingly, phase 1
      adhesion was inversely correlated with GSH levels but not with the GSSG/GSH
      ratio, whereas phase 2 neutrophil adhesion was positively correlated with
      GSSG/GSH ratio but not with GSH levels. Intercellular adhesion molecule-1 and P
      selectin-specific monoclonal antibodies attenuated the increased neutrophil
      adhesion during both phases, whereas an anti-E-selectin monoclonal antibody also
      attenuated the phase 2 response. Pretreatment with actinomycin D and
      cycloheximide or with competing ds-oligonucleotides that contained nuclear factor
      kappaB or activator protein-1 cognate DNA sequences significantly attenuated the
      phase 2 response, which implicated a role for de novo protein synthesis. Surface
      expression of intercellular adhesion molecule-1, P-selectin, and E-selectin on
      HUVECs correlated with the phase 1 and 2 neutrophil adhesion responses. This
      study demonstrates that changes in endothelial cell GSSG/GSH cause transcription
      independent and transcription-dependent surface expression of different
      endothelial cell adhesion molecules, which leads to a 2-phase neutrophil
      endothelial adhesion response.

PMID- 10082474
TI  - Endothelial injuries of coronary arteries distal to thrombotic sites: role of
      adhesive interaction between endothelial P-selectin and leukocyte sialyl LewisX.
AB  - Intracoronary thrombus formation is associated with epicardial vasoconstriction
      distal to the thrombotic site. To investigate the mechanisms of abnormal
      vasomotor function of the artery distal to the thrombotic site, we studied
      coronary vessels in dogs with cyclic flow variations (CFVs) of the left anterior
      descending coronary artery (LAD) stenosis with endothelial injury. Coronary rings
      isolated from the LAD (proximal, stenotic, and distal sites) and control
      circumflex coronary arteries were tested for responsiveness to endothelium
      dependent (acetylcholine and A23187) and endothelium-independent vasodilators
      (NaNO2). Endothelium-independent relaxation was intact in all 4 sites.
      Endothelium-dependent relaxation was intact in the control and proximal sites and
      impaired in the stenotic sites. Relaxations not only to acetylcholine and A23187
      but also to serotonin, ADP, and thrombin were impaired in the distal sites after
      observing CFVs for 80 minutes. Electron microscopy revealed the loss of
      endothelial integrity with leukocyte adherence to the endothelium in the distal
      sites. Immunohistochemical expression of P-selectin on the endothelial cells was
      more upregulated in the distal site than in the proximal site, and P-selectin
      mRNA expression was significantly greater in the ischemic region distal to the
      thrombotic site than in the proximal nonischemic region. PB1.3, a neutralizing
      monoclonal antibody against P-selectin, and sialyl LewisX (SLeX)-containing
      oligosaccharide SLeX, a carbohydrate analogue of selectin ligand, preserved
      endothelial function without affecting CFVs. SLeX-containing oligosaccharide
      preserved endothelial integrity of the distal site and inhibited P-selectin
      expression of the distal site. Thus, the adhesive interaction between endothelial
      P-selectin and leukocyte SLeX may play an important role in endothelial injuries
      of the coronary artery distal to the thrombotic site.

PMID- 10082475
TI  - Expression and distribution of the type 1 and type 3 inositol 1,4, 5
      trisphosphate receptor in developing vascular smooth muscle.
AB  - The recent discoveries of inositol 1,4,5-trisphosphate (IP3) receptor subtypes
      with different affinities for IP3 and their potential involvement in development
      has important consequences for vascular smooth muscle. This study has examined
      the expression and distribution of the type 1 and type 3 IP3 receptor subtypes in
      developing rat vascular smooth muscles. Immunoblotting of portal vein and aorta
      from neonatal (2 to 4 days) and fully developed (6 weeks) rats revealed
      significantly higher levels of the type 3 IP3 receptor expression in neonatal,
      compared with developed, vascular smooth muscles. In contrast, expression of the
      type 1 IP3 receptor in neonates was lower compared with developed vascular smooth
      muscles. Immunolocalization of the type 3 IP3 receptors in neonatal tissues
      revealed that staining corresponded to the distribution of the sarcoplasmic
      reticulum (visualized by osmium ferricyanide staining of thin tissue sections),
      which suggested localization of the type 3 IP3 receptor throughout the
      sarcoplasmic reticulum network. We conclude that type 3 IP3 receptors are the
      predominant subtype in the development of vascular smooth muscle and are
      distributed throughout the sarcoplasmic reticulum in these cells. The switch in
      isoforms of the IP3 receptor during development from the type 3 with low affinity
      for IP3 to the higher-affinity type 1 receptor may play a role in calcium
      mediated regulation of developing vascular smooth muscle.

PMID- 10082476
TI  - Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by
      induction of p21(waf1/cip1/sdi1) and p53.
AB  - Tranilast, which is an antiallergic drug, has a potent effect on preventing
      postangioplasty restenosis. To elucidate this mechanism, we studied the effect of
      tranilast on the proliferation of vascular smooth muscle cells (SMCs) in vitro
      and in vivo. Tranilast decreased the growth rate of SMCs stimulated by either 10%
      FBS or platelet-derived growth factor. The IC50 value, evaluated as cell number,
      was 100 micromol/L. These inhibitory effects were associated with inhibition of
      the retinoblastoma gene product (pRb) phosphorylation. Because pRb
      phosphorylation is regulated by cyclin-dependent kinases (CDK), we investigated
      CDK2 and CDK4 activities and the expression of CDK inhibitor p21(waf1/cip1/sdi1)
      (p21). When SMCs were stimulated by 10% FBS or platelet-derived growth factor,
      CDK2 and CDK4 activities reached a maximum near the G1/S transition. Tranilast
      suppressed their activities by >80% without reduction of CDK2/cyclin E and
      CDK4/cyclin D1 protein levels. These inhibitory effects were associated with
      enhanced expression of p21 and elevated complexing of p21 with CDK2/CDK4. Next,
      rat balloon-injured carotid artery was analyzed for intimal thickening and p21
      expression. Tranilast-treated rats had a 70% (P<0.001) smaller neointima/media
      area ratio at 14 days after balloon injury compared with the controls.
      Immunohistochemical staining demonstrated that, in tranilast-treated rats, p21
      was already present in the neointima at day 7 and strongly expressed throughout
      the neointima at day 14. In control rats, p21 was not observed in the neointima
      at day 7 but was sparsely expressed at day 14. These data demonstrate that
      inhibition of CDK2/CDK4 activities by the increased expression of p21 may be one
      mechanism by which tranilast inhibits SMC proliferation and prevents
      postangioplasty restenosis.

PMID- 10082477
TI  - Potential molecular basis of different physiological properties of the transient
      outward K+ current in rabbit and human atrial myocytes.
AB  - The properties of the transient outward current (Ito) differ between rabbit and
      human atrial myocytes. In particular, rabbit Ito is known to recover more slowly
      than its human counterpart and to show much more frequency dependence. To assess
      the possibility that these physiological differences may reflect differing
      expression of K+ channel subunit gene products, we used a combination of whole
      cell voltage-clamp, heterologous expression, pharmacological, antisense, and
      Western blot techniques. The inactivation of Ito in rabbit atrial myocytes was
      significantly slowed by hydrogen peroxide, with human Ito being unaffected. Use
      dependent unblocking with 4-aminopyridine was not seen for rabbit Ito nor for
      Kv1.4 currents in Xenopus oocytes, whereas human Ito showed strong use-dependent
      unblock (as did Kv4 currents). Western blots indicated the presence of Kv4
      proteins in both human and rabbit atrial membranes, but Kv1.4 was only detected
      in the rabbit. Antisense oligodeoxynucleotides directed against Kv4.3, Kv4.2, or
      Kv1.4 subunit sequences significantly inhibited Ito current density in cultured
      rabbit atrial myocytes, whereas only Kv4.3 antisense significantly inhibited Ito
      in human cells. Neither mismatch oligodeoxynucleotides nor vehicle altered
      currents in either species. We conclude that, unlike human atrial myocytes,
      rabbit atrial myocytes express Kv1.4 channel subunits, which likely contribute to
      a number of important physiological differences in Ito properties between the
      species. To our knowledge, these studies constitute the first demonstration of a
      functional role for Kv1.4 channels in cardiac membranes and provide insights into
      the molecular mechanisms of an important cardiac repolarizing current.

PMID- 10082478
TI  - Mechanisms of altered excitation-contraction coupling in canine tachycardia
      induced heart failure, I: experimental studies.
AB  - Pacing-induced heart failure in the dog recapitulates many of the
      electrophysiological and hemodynamic abnormalities of the human disease; however,
      the mechanisms underlying altered Ca2+ handling have not been investigated in
      this model. We now show that left ventricular midmyocardial myocytes isolated
      from dogs subjected to 3 to 4 weeks of rapid pacing have prolonged action
      potentials and Ca2+ transients with reduced peaks, but durations approximately 3
      fold longer than controls. To discriminate between action potential effects on
      Ca2+ kinetics and direct changes in Ca2+ regulatory processes, voltage-clamp
      steps were used to examine the time constant for cytosolic Ca2+ removal (tauCa).
      tauCa was prolonged by just 35% in myocytes from failing hearts after fixed
      voltage steps in physiological solutions (tauCa control, 216+/-25 ms, n=17; tauCa
      failing, 292+/-23 ms, n=22; P<0.05), but this difference was markedly accentuated
      when Na+/Ca2+ exchange was eliminated (tauCa control, 282+/-30 ms, n=13; tauCa
      failing, 576+/-83 ms, n=11; P<0. 005). Impaired sarcoplasmic reticular (SR) Ca2+
      uptake and a greater dependence on Na+/Ca2+ exchange for cytosolic Ca2+ removal
      was confirmed by inhibiting SR Ca2+ ATPase with cyclopiazonic acid, which slowed
      Ca2+ removal more in control than in failing myocytes. beta-Adrenergic
      stimulation of SR Ca2+ uptake in cells from failing hearts sufficed only to
      accelerate tauCa to the range of unstimulated controls. Protein levels of
      SERCA2a, phospholamban, and Na+/Ca2+ exchanger revealed a pattern of changes
      qualitatively similar to the functional measurements; SERCA2a and phospholamban
      were both reduced in failing hearts by 28%, and Na+/Ca2+ exchange protein was
      increased 104% relative to controls. Thus, SR Ca2+ uptake is markedly
      downregulated in failing hearts, but this defect is partially compensated by
      enhanced Na+/Ca2+ exchange. The alterations are similar to those reported in
      human heart failure, which reinforces the utility of the pacing-induced dog model
      as a surrogate for the human disease.

PMID- 10082479
TI  - Mechanisms of altered excitation-contraction coupling in canine tachycardia
      induced heart failure, II: model studies.
AB  - Ca2+ transients measured in failing human ventricular myocytes exhibit reduced
      amplitude, slowed relaxation, and blunted frequency dependence. In the companion
      article (O'Rourke B, Kass DA, Tomaselli GF, Kaab S, Tunin R, Marban E. Mechanisms
      of altered excitation-contraction coupling in canine tachycardia-induced heart,
      I: experimental studies. Circ Res. 1999;84:562-570), O'Rourke et al show that
      Ca2+ transients recorded in myocytes isolated from canine hearts subjected to the
      tachycardia pacing protocol exhibit similar responses. Analyses of protein levels
      in these failing hearts reveal that both SR Ca2+ ATPase and phospholamban are
      decreased on average by 28% and that Na+/Ca2+ exchanger (NCX) protein is
      increased on average by 104%. In this article, we present a model of the canine
      midmyocardial ventricular action potential and Ca2+ transient. The model is used
      to estimate the degree of functional upregulation and downregulation of NCX and
      SR Ca2+ ATPase in heart failure using data obtained from 2 different experimental
      protocols. Model estimates of average SR Ca2+ ATPase functional downregulation
      obtained using these experimental protocols are 49% and 62%. Model estimates of
      average NCX functional upregulation range are 38% and 75%. Simulation of voltage
      clamp Ca2+ transients indicates that such changes are sufficient to account for
      the reduced amplitude, altered shape, and slowed relaxation of Ca2+ transients in
      the failing canine heart. Model analyses also suggest that altered expression of
      Ca2+ handling proteins plays a significant role in prolongation of action
      potential duration in failing canine myocytes.

PMID- 10082480
TI  - Isoform-selective activation of protein kinase C by nitric oxide in the heart of
      conscious rabbits: a signaling mechanism for both nitric oxide-induced and
      ischemia-induced preconditioning.
AB  - Although isoform-selective translocation of protein kinase C (PKC) epsilon
      appears to play an important role in the late phase of ischemic preconditioning
      (PC), the mechanism(s) responsible for such translocation remains unclear.
      Furthermore, the signaling pathway that leads to the development of late PC after
      exogenous administration of NO in the absence of ischemia (NO donor-induced late
      PC) is unknown. In the present study we tested the hypothesis that NO activates
      PKC and that this is the mechanism for the development of both ischemia-induced
      and NO donor-induced late PC. A total of 95 chronically instrumented, conscious
      rabbits were used. In rabbits subjected to ischemic PC (six 4-minute occlusion/4
      minute reperfusion cycles), administration of the NO synthase inhibitor Nomega
      nitro-L-arginine (group III), at doses previously shown to block the development
      of late PC, completely blocked the ischemic PC-induced translocation of
      PKCepsilon but not of PKCeta, indicating that increased formation of NO is an
      essential mechanism whereby brief ischemia activates the epsilon isoform of PKC.
      Conversely, a translocation of PKCepsilon and -eta quantitatively similar to that
      induced by ischemic PC could be reproduced pharmacologically with the
      administration of 2 structurally unrelated NO donors, diethylenetriamine/NO
      (DETA/NO) and S-nitroso-N-acetylpenicillamine (SNAP), at doses previously shown
      to elicit a late PC effect. The particulate fraction of PKCepsilon increased from
      35+/-2% of total in the control group (group I) to 60+/-1% after ischemic PC
      (group II) (P<0.05), to 54+/-2% after SNAP (group IV) (P<0.05) and to 52+/-2%
      after DETA/NO (group V) (P<0.05). The particulate fraction of PKCeta rose from
      66+/-5% in the control group to 86+/-3% after ischemic PC (P<0.05), to 88+/-2%
      after SNAP (P<0.05) and to 85+/-1% after DETA/NO (P<0.05). Neither ischemic PC
      nor NO donors had any appreciable effect on the subcellular distribution of
      PKCalpha, -beta1, -beta2, -gamma, -delta, - micro, or -iota/lambda; on total PKC
      activity; or on the subcellular distribution of total PKC activity. Thus, the
      effects of SNAP and DETA/NO on PKC closely resembled those of ischemic PC. The
      DETA/NO-induced translocation of PKCepsilon (but not that of PKCeta) was
      completely prevented by the administration of the PKC inhibitor chelerythrine at
      a dose of 5 mg/kg (group VI) (particulate fraction of PKCepsilon, 38+/-4% of
      total, P<0.05 versus group V; particulate fraction of PKCeta, 79+/-2% of total).
      The same dose of chelerythrine completely prevented the DETA/NO-induced late PC
      effect against both myocardial stunning (groups VII through X) and myocardial
      infarction (groups XI through XV), indicating that NO donors induce late PC by
      activating PKC and that among the 10 isozymes of PKC expressed in the rabbit
      heart, the epsilon isotype is specifically involved in the development of this
      form of pharmacological PC. In all groups examined (groups I through VI), the
      changes in the subcellular distribution of PKCepsilon protein were associated
      with parallel changes in PKCepsilon isoform-selective activity, whereas total PKC
      activity was not significantly altered. Taken together, the results provide
      direct evidence that isoform-selective activation of PKCepsilon is a critical
      step in the signaling pathway whereby NO initiates the development of a late PC
      effect both after an ischemic stimulus (endogenous NO) and after treatment with
      NO-releasing agents (exogenous NO). To our knowledge, this is also the first
      report that NO can activate PKC in the heart. The finding that NO can promote
      isoform-specific activation of PKC identifies a new biological function of this
      radical and a new mechanism in the signaling cascade of ischemic PC and may also
      have important implications for other pathophysiological conditions in which NO
      is involved and for nitrate therapy.

PMID- 10082481
TI  - Structure of the type B human natriuretic peptide receptor gene and association
      of a novel microsatellite polymorphism with essential hypertension.
AB  - The natriuretic peptide (NP) system may play a crucial role in development of
      essential hypertension (EH). C-type NP dilates arteries and lowers blood pressure
      and inhibits proliferation of vascular smooth muscle cells via the type B NP
      receptor (NPR-B). However, the association of the human NPR-B gene with EH has
      not been studied, because little is known about the genomic organization of this
      gene. We designed oligonucleotide primers based on the cDNA sequence of the human
      NPR-B gene, and long-range polymerase chain reaction (PCR) was performed. The
      amplified fragments were sequenced directly, and the exon/intron organization of
      the human NPR-B gene was determined. The gene, which spans approximately 16.5
      kbp, is composed of 22 exons, and the intron-exon junctions follow the GT-AG
      rule. Seven hundred fifty base pairs of the 5'-flanking region were sequenced
      using a thermal asymmetric interlaced-PCR (TAIL-PCR) method. This region contains
      10 potential Sp1 binding sites and lacks a TATA box. Rapid amplification of cDNA
      ends (RACE) revealed the transcriptional start site at -14 bp. A CA/GT
      microsatellite repeat was identified with a hybridization-based method and was
      converted to a sequence-tagged site (STS). The GT microsatellite repeat was
      localized to intron 2 approximately 150 bp downstream of the exon-intron
      junction. Two alleles, (GT)10 and (GT)11, were detected in both EH patients and
      age-matched normotensive (NT) controls. Multiple logistic linear regression
      analysis indicated that the NPR-B genotype is associated significantly with EH
      (odds ratio 1.55; 95% confidence interval, 1.02 to 2.35). The (GT)11 frequency
      was 0.316 (65/206) for the EH group and 0.218 (44/202) for the NT group and
      differed significantly between the EH and NT groups (chi2=4.97, P=0.026). The
      structural organization of the human NPR-B gene was determined, and a novel GT
      repeat polymorphism, which associated with EH, was identified. These results
      suggest that one cause of EH is a mutation in this gene or a closely related gene
      or region.

PMID- 10082482
TI  - Molecular mechanisms of endothelin-1-induced cell-cycle progression: involvement
      of extracellular signal-regulated kinase, protein kinase C, and
      phosphatidylinositol 3-kinase at distinct points.
AB  - Although it is well established that endothelin-1 (ET-1) has not only
      vasoconstrictive effects but also mitogenic effects, which seem to be implicated
      in vascular remodeling, little is known about the molecular mechanisms by which
      ET-1 induces cell-cycle progression. In this study, we examined the effects of ET
      1 on the cell-cycle regulatory machinery, including cyclins, cyclin-dependent
      kinase (cdk), and cdk inhibitors in NIH3T3 cells. ET-1 increased cyclin D1
      protein (5.1+/-1.9-fold increase, 8 hours after stimulation, P<0.05), cdk4 kinase
      activity (2.8+/-0. 5-fold increase, 12 hours after stimulation, P<0.01), and cdk2
      kinase activity (2.1+/-0.4-fold increase, 16 hours after stimulation, P<0.05) in
      a time- and dose-dependent manner. ET-1-induced increase in cyclin D1 protein,
      and cdk4 kinase activity was not significantly inhibited by an inhibitor of the
      mitogen-activated protein kinase kinase 1/2, PD98059, nor by the protein kinase C
      inhibitor calphostin C, whereas ET-1-induced upregulation of cyclin D1 protein
      and cdk4 kinase activity was significantly inhibited by the phosphatidylinositol
      3-kinase inhibitor LY294002. In contrast, ET-1-induced activation of cdk2 kinase
      was significantly inhibited by PD98059, calphostin C, and LY294002. ET-1
      increased 3H-thymidine uptake in a time-dependent fashion (0 hours, 4216+/-264
      cpm per well; 8 hours, 5025+/-197 cpm per well; 16 hours, 9239+/-79 cpm per well,
      P<0.001 versus 0 hours). ET-1-induced increase in 3H-thymidine uptake was
      significantly inhibited by PD98059, calphostin C, and LY294002. These results
      suggest that ET-1-induced cell-cycle progression is, at least in part, mediated
      by the extracellular signal-regulated kinase, protein kinase C, and
      phosphatidylinositol 3-kinase and that those pathways may be involved in the
      progression of the cell cycle at distinct points.

PMID- 10082483
TI  - Molecular identity of Ito: Kv1.4 redux.

PMID- 10082484
TI  - Hypertension : the second five years.

PMID- 10082485
TI  - Parental hyperdynamic circulation predicts insulin resistance in offspring: The
      Tecumseh Offspring Study.
AB  - Controversy surrounds the pathogenetic mechanisms of the relationship between
      hyperdynamic circulation and insulin resistance. Two hundred eight children and
      young adults (mean age, 17.2+/-3.0 years; range, 11 to 26 years) from the
      Tecumseh Offspring Study whose parents had been assessed with Doppler
      echocardiography at the age of 34 years during the previous Tecumseh Blood
      Pressure Study were considered for this analysis. Offspring data were stratified
      according to tertiles of parental cardiac index. Parents in the top cardiac index
      tertile had increased heart rate (P=0.001), stroke volume (P=0.0001), left
      ventricular fractional shortening (P=0.02), and plasma epinephrine (P=0.02)
      compared with parents in the other tertiles. Body mass index (BMI) and blood
      pressure were similar in all groups. Offspring of parents with a high cardiac
      index had greater BMI (P=0.001), skinfold thickness (P=0.008), and waist/hip
      ratio (P=0.02), higher diastolic blood pressure (P=0.02) and plasma insulin level
      (P=0.001), and higher heart rate during Stroop's color test (P=0.02) than
      offspring of parents with a lower cardiac index. In a multivariate regression
      analysis, offspring BMI was predicted by parental BMI and cardiac index (P=0.0001
      and 0.003, respectively). The mother-child relationship explained most of the
      cardiac index-BMI association. In summary, parental hyperdynamic circulation was
      an important predictor of overweight, abnormal fat distribution, increased blood
      pressure, and hyperinsulinemia in offspring. Our results illustrate the
      complexity of interaction between a genetic tendency and its phenotypic
      expression. We speculate that the degree of beta-adrenergic responsiveness may be
      a major determinant of the phenotypic differences between the parents and
      offspring found in this study.

PMID- 10082486
TI  - Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1
      diabetes.
AB  - Hyperglycemia causes capillary vasodilation and high glomerular capillary
      hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1
      diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I
      converting enzyme (ACE) gene can modulate risk of nephropathy due to
      hyperglycemia, and the II genotype (producing low plasma ACE concentrations and
      probably reduced renal angiotensin II generation and kinin inactivation) may
      protect against diabetic nephropathy. We tested the possible interaction between
      ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia
      ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9
      normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and
      18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per
      1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/
      10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/
      16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7%
      and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects:
      P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal
      hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly
      preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE
      concentration (P=0.024); this was not observed in subjects with the II genotype.
      Thus, type 1 diabetic individuals with the II genotype are resistant to
      glomerular changes induced by hyperglycemia, providing a basis for their reduced
      risk of nephropathy.

PMID- 10082487
TI  - Insulin sensitivity is related to physical fitness and exercise blood pressure to
      structural vascular properties in young men.
AB  - Insulin resistance is related to physical inactivity, which is a risk factor for
      cardiovascular disease and death. Moreover, blood pressure responses during the
      first 6 minutes of an exercise test (600 kilo/pound/meter [kpm] per min) are more
      predictive for cardiovascular morbidity and mortality than blood pressure at
      rest, which could reflect that exercise blood pressure correlates more closely to
      peripheral structural vascular changes than casual blood pressure. We have
      recently shown a correlation between insulin resistance and minimal forearm
      vascular resistance (MFVR) in young men recruited from the highest blood pressure
      percentiles during a military draft session. In the present study, we tested the
      hypotheses that insulin sensitivity relates to physical fitness and that blood
      pressure responses during an exercise test relate to peripheral structural
      vascular changes in these men; we also tested whether these findings were
      interrelated. We assessed insulin sensitivity and physical fitness in 27 young
      men randomly selected from the cohort having a blood pressure of 140/90 mm Hg or
      higher during the compulsory military draft session in Oslo. Insulin sensitivity
      correlated with physical fitness (r=0.58, P=0.002). Systolic blood pressure after
      6 minutes of exercise (600 kpm/min) correlated with MFVR (r=0.46, P=0.015). MFVR
      and physical fitness independently explained 60% of the variation in insulin
      sensitivity, and MFVR independently explained 19% of the variation of systolic
      blood pressure after 6 minutes of exercise. In conclusion, insulin sensitivity is
      related to physical fitness and exercise blood pressure to structural vascular
      properties in these young men.

PMID- 10082488
TI  - Assessment of arterial compliance by carotid midwall strain-stress relation in
      normotensive adults.
AB  - Examining left ventricular midwall as opposed to endocardial mechanics enhances
      understanding of left ventricular function in individuals with abnormal cardiac
      geometry. Accordingly, we used carotid ultrasound and applanation tonometry of
      arterial pressure to derive carotid midwall strain and its relation to carotid
      peak-systolic and end-diastolic stresses in 82 apparently normal, employed
      subjects (56 men, 26 women; median age, 47 years; 70% white; 21% overweight) with
      no evidence of coronary or valvular heart disease. Regression equations relating
      carotid luminal and midwall strain to the increment in carotid stress during
      systole (Deltacarotid stress) were used to predict strain for the observed
      Deltastress. Observed/predicted carotid luminal or midwall strain was calculated
      as a measure of carotid luminal or midwall strain for imposed stress, termed
      stress-corrected strain. Midwall carotid strain was similar in women and men but
      was negatively related to older age (r=-0.35, P=0.001) and higher body mass index
      (r=-0.31, P=0.005) and brachial and carotid blood pressure (r=-0.30 to -0.45, all
      P<0.01). The pulsatile change in arterial load, measured by Deltacarotid stress,
      was positively related to midwall strain (r=0. 44, P<0.001) more closely than was
      carotid luminal strain. Regression analyses revealed that carotid midwall strain
      was positively related to Deltastress, with additional negative relations to age
      and carotid diastolic diameter (all P<0.001). Stress-corrected carotid midwall
      strain was strongly and negatively correlated with midwall elastic modulus and
      Young's modulus (both r=-0.77, P<0.001), followed by elastic modulus (r=-0.74,
      P<0.001), midwall Young's modulus (r=-0.73, P<0.001), midwall stiffness index (r=
      0.70, P<0.001), and stiffness index (r=-0.66, P<0.001). Thus, in normal adults,
      carotid midwall strain is unrelated to gender, is positively related to pulsatile
      carotid load as measured by Deltacarotid stress, and is negatively related to
      age, overweight, and standard measures of arterial stiffness.

PMID- 10082489
TI  - Assessment of arterial compliance by carotid midwall strain-stress relation in
      hypertension.
AB  - To elucidate the relations between arterial hypertrophy and compliance in
      hypertension, we studied 205 unmedicated hypertensive patients (129 men and 76
      women) and 82 normotensive adults (56 men and 26 women) from an employed
      population by carotid ultrasound, noninvasive applanation tonometry, and
      echocardiography. Carotid midwall strain and circumferential stress were
      calculated at end diastole and peak systole. The relations of luminal and midwall
      strain to the increment in circumferential stress from end diastole to peak
      systole (Deltacarotid stress in normal subjects) were used to calculate ratios of
      observed/predicted carotid luminal and midwall strain. Mean stress-corrected
      luminal strain (82+/-26%) and midwall strain (78+/-23%) were lower (both P<0.001)
      in hypertensive patients than in normal adults. Stress-corrected luminal strain
      identified 14% of hypertensive patients with low arterial compliance, while
      stress-corrected midwall strain was low in 18% of patients. Patients with
      subnormal carotid midwall strain were older (61+/-12 versus 54+/-12 years,
      P<0.01) and had larger carotid diameters (6. 6+/-0.8 versus 5.7+/-0.8 mm,
      P=0.002) and higher brachial pulse pressures (71+/-25 versus 63+/-17 mm Hg,
      P<0.05) than other patients. Patients with arterial hypertrophy had lower stress
      corrected midwall strain than those without hypertrophy (70+/-24% versus 79+/
      23%, P=0.05), whereas no difference was observed in stress-corrected luminal
      strain (P=0.40). Stress-corrected midwall strain tended to be lower in patients
      with discrete atherosclerotic plaques than in those without (74+/-20% versus 79+/
      24%, P=0.15). Compared with patients with normal left ventricular geometry, those
      with concentric hypertrophy had larger carotid diameters (6.6+/-0.7 versus 5.8+/
      0.9 mm, P<0.05) and lower stress-corrected luminal strain (62+/-11% versus 85+/
      25%, P<0.05) and midwall strain (59+/-10% versus 81+/-22%, P<0.05). Therefore,
      stress-corrected midwall strain identifies patients with reduced arterial
      compliance, increased arterial wall thickness, and abnormal left ventricular
      geometry better than conventional measures based on arterial lumen diameters.

PMID- 10082490
TI  - Stroke volume/pulse pressure ratio and cardiovascular risk in arterial
      hypertension.
AB  - Ratio of stroke volume (SV, M-mode echocardiography) to pulse pressure (PP) has
      been proposed as an estimate of total arterial compliance and has been shown to
      be related to body size, age, and heart rate in normal adults. SV/PP was
      estimated in 294 hypertensive patients (98 women) as a raw value by use of
      SV/body surface area (SVi) and by the ratio of SV/PP to the value predicted by a
      previously developed equation (%SV/PP). At baseline, the 50 patients who had
      cardiovascular events over the following 10 years exhibited higher PP and lower
      SV/PP, SVi/PP, and %SV/PP (all P<0.008) than patients without events. Crude risk
      of follow-up total and fatal cardiovascular events increased with increasing
      level of PP and decreasing SV/PP, SVi/PP, and %SV/PP (all P<0.002). In
      multivariate logistic regression models with continuous covariates, the risk of
      total cardiovascular events was independently related to increasing age
      (P<0.0001) and left ventricular (LV) mass index (P<0.003) and decreasing values
      of %SV/PP (P<0.006) but not to increasing systolic, pulse, or mean blood pressure
      or gender. Similar although less strong results were obtained with the use of
      SVi/PP (P<0.02), whereas SV/PP did not enter the model as an independent
      predictor. Risk of cardiovascular death was only predicted by age and LV mass
      index. The %SV/PP was also an independent predictor of total cardiovascular
      events in Cox proportional hazards analysis (exp[b]: 2.49, P<0.001) independent
      of age (exp[b]: 1.05, P<0.003) and LV mass index (exp[b]: 1.02, P<0.0003),
      whereas no effect was detected for height. Thus, in patients with arterial
      hypertension, a reduced ratio of M-mode echocardiographic SV/PP as a percentage
      of the value predicted by demographic variables is a predictor of cardiovascular
      morbid events independent of age and LV mass index.

PMID- 10082491
TI  - Distribution of lamellar deformations: implications for properties of the
      arterial media.
AB  - Most computations of arterial mechanics treat the wall as a mechanically
      homogeneous body, but there are no data to support or refute this. To evaluate
      this assumption, experiments were performed that measured the deformation of 4
      elastic lamellae located at 4 equidistant points across the thickness of the
      media. Data were obtained at 25-mm Hg pressure steps between 0 and 200 mm Hg. To
      satisfy the constraints of incompressibility in an isovolumetric cylinder, the
      innermost structures must undergo larger deformations than the outermost
      structures. This manifests as thinning of the wall. Therefore, each experiment
      was performed twice: once with a vessel segment in its normal cylindrical
      configuration, and again with a contiguous vessel segment turned inside-out to
      form an inverted cylinder. The deformations of individual lamellae obtained in
      normal and inverted vessel segments were averaged to determine their extensions
      independent of location. Results showed that the extensibilities of the lamellae
      were equal at all 4 anatomic locations across the media, suggesting equal
      stiffnesses of the lamellae. Other studies were performed to examine the
      distribution of the circumferential retractions of the lamellae that occurs when
      a vessel is extended longitudinally. Results showed that circumferential
      retraction also was distributed uniformly across the wall. These findings
      demonstrate that the elastic lamellae behave uniformly in both the
      circumferential and longitudinal directions at different locations across the
      wall thickness. Because of the interlocked structure of the elastin, muscle, and
      collagen in the media, these findings suggest that although the media is
      histologically heterogeneous, it acts mechanically as a homogeneous material.

PMID- 10082492
TI  - Diastolic compliance is reduced in obese rabbits.
AB  - Obesity often leads to symptoms of cardiopulmonary congestion associated with
      normal systolic but abnormal diastolic function. This study analyzed alterations
      in passive diastolic compliance in obesity using the rabbit model. New Zealand
      White rabbits were fed a normal (n=8) or 10% added fat diet (n=8). After 12
      weeks, rabbits fed the high fat diet developed obesity (5.34+/-0.11 versus 3.68+/
      0. 04 kg, P</=0.05) and left ventricular hypertrophy (1.37+/-0.07 versus 0.98+/
      0.03 g dry weight, P</=0.05). Compliance was assessed with the isolated heart
      preparation by analyzing the passive end-diastolic left ventricular pressure
      volume relationship. The pressure-volume relation was fit to an exponential
      function by regression analysis; results showed that the modulus of stiffness was
      greater in obese than in lean rabbits (1.21+/-0.16 versus 0. 83+/-0.05,
      P</=0.05), indicating that diastolic compliance was reduced. Computer simulation
      analyses suggested that an isolated reduction in diastolic compliance may
      contribute to elevated cardiac filling pressures and exercise intolerance. These
      data suggest that diastolic compliance is reduced early in the development of
      obesity and may be an important component in the reduction of cardiac reserve in
      obesity.

PMID- 10082493
TI  - Endothelin system-dependent cardiac remodeling in renovascular hypertension.
AB  - The aim of the present study was to analyze whether the cardiac endothelin system
      contributes to cardiac remodeling in rats with 2-kidney, 1 clip (2K1C)
      renovascular hypertension. The endothelin system seems to be a promising
      candidate for cardiac remodeling because endothelin (ET)-1 promotes growth of
      cardiomyocytes in vitro and induces cardiac collagen synthesis. The activity of
      the cardiac endothelin system was analyzed by measuring cardiac tissue big ET-1
      and ET-1 concentrations as well as by estimating the cardiac expression of the
      ETA and ETB receptors 10 days, 4 weeks, and 12 weeks after the renal artery was
      clipped. The effects of long-term treatment with ETA, ETB, and combined ETA/ETB
      receptor antagonists on cardiac hypertrophy, media/lumen ratio of intracardiac
      arteries, and left ventricular fibrosis were also analyzed. This study
      demonstrated that the overall left ventricular cardiac endothelin system has a
      similar activity in the early, middle, and late stages of 2K1C renovascular
      hypertension compared with sham-operated controls. Fibrosis of the left ventricle
      and hypertrophy of intracardiac arteries, however, were markedly altered after
      long-term treatment with endothelin receptor antagonists in a blood pressure
      independent manner. These 2 effects are mediated by different subtypes of
      endothelin receptors. ETA receptor blockade completely normalized the hypertrophy
      of intracardiac arteries (P<0. 01 compared with 2K1C without treatment) in
      renovascular hypertension, whereas the ETB antagonist reduced cardiac fibrosis of
      the left ventricle (P<0.001 compared with 2K1C without treatment) to baseline
      values. This study demonstrates that the cardiac endothelin system plays an
      important role in the development of cardiac fibrosis as well as in hypertrophy
      of intracardiac arteries in 2K1C renovascular hypertensive rats.

PMID- 10082494
TI  - Kinin B1 receptor antagonists containing alpha-methyl-L-phenylalanine: in vitro
      and in vivo antagonistic activities.
AB  - -To protect from metabolism and to improve potency of the AcLys-[D
      betaNal7,Ile8]desArg9-bradykinin (BK) (R 715), we prepared and tested 3 analogues
      containing alpha-methyl-L-Phe ([alphaMe]Phe) in position 5: these are the AcLys
      [(alphaMe)Phe5,D-betaNal7, Ile8]desArg9BK (R 892), Lys-Lys-[(alphaMe)Phe5,D
      betaNal7, Ile8]desArg9BK (R 913), and AcLys-Lys-[(alphaMe)Phe5,D-betaNal7,
      Ile8]desArg9BK (R 914). The new compounds were tested against the contractile
      effect induced by desArg9BK on 2 B1 receptor bioassays, the human umbilical vein,
      and the rabbit aorta. Their antagonistic activities were compared with those of
      the early prototypes (Lys-[Leu8]desArg9BK and [Leu8]desArg9BK) and with other
      recently described peptide antagonists. The 3 (alphaMe)Phe analogues showed high
      antagonistic potencies (pA2) at both the human (8.8, 7.7, and 8. 7, respectively)
      and rabbit (8.6, 7.8, and 8.6, respectively) B1 receptors. No antagonistic
      effects (pA2<5) were observed on the B2 receptors that mediate the contractile
      effects of BK on the human umbilical vein, the rabbit jugular vein, and the
      guinea pig ileum. Moreover, these new B1 antagonists were found to be resistant
      to in vitro degradation by purified angiotensin-converting enzyme from rabbit
      lung. The Nalpha-acetylated forms, R 892 and R 914, were resistant to
      aminopeptidases from human plasma. In vivo antagonistic potencies (ID50) of B1
      receptor antagonists were evaluated in anesthetized lipopolysaccharide-treated
      (for B1 receptor) and nontreated (for B2 receptor) rabbits against the
      hypotensive effects of exogenous desArg9BK and BK. R 892 efficiently inhibited
      (ID50 2.8 nmol/kg IV) hypotension induced by desArg9BK without affecting that
      evoked by BK (ID50 >600 nmol/kg IV). Conversely, the peptide antagonists Lys-Lys
      [Hyp3,Igl5,D-Igl7,Oic8]desArg9BK (B 9858) and DArg-[Hyp3,Thi5,D-Tic7,Oic8]
      desArg9BK (S 0765) showed dual B1/B2 receptor antagonism in vitro and in vivo. It
      is concluded that R 892 and congeners provide selective, highly potent, and
      metabolically stable B1 kinin receptor antagonists that can be useful for the
      assessment of the physiological and pathological roles of kinin B1 receptors.

PMID- 10082495
TI  - Chronic bradykinin infusion and receptor blockade in angiotensin II hypertension
      in rats.
AB  - The influence of endogenous bradykinin(BK) on the control of arterial pressure
      and the development of cardiac hypertrophy was assessed in chronically
      angiotensin II(Ang II)-infused rats (200 ng. kg-1. min-1) through the effects of
      concomitant infusion of 3 doses of BK (15 ng. kg-1. d-1, 100 ng. kg-1. d-1 and
      100 ng. kg-1. min-1 ie, 144 000 ng. kg-1. d-1) or BK-blockade by Hoe140 (300
      microg. kg-1. d-1) for 10 days. In Ang II-infused rats, tail-cuff pressure
      increased from 124+/-3 to 174+/-6 mm Hg (P<0.001). The pressor effect of Ang II
      was not affected by simultaneous infusion of BK or Hoe140. At the end of the
      experiments, cardiac mass was higher in rats infused with Ang II alone (3.56+/
      0.10 versus 2.89+/-0.05 mg/g in untreated controls, P<0.01) and the development
      of cardiac hypertrophy was not modified by administration of the 3 doses of BK or
      Hoe140. In addition, the fall in cardiac output associated with Ang II was
      prevented only by the moderate and high doses of BK, mainly through an increase
      in stroke volume and a decrease in total peripheral resistance. In the same way,
      the renal vasoconstrictor effect of Ang II was abolished by the medium and high
      dose of BK. Hoe140 did not affect cardiac output or renal blood flow in this
      model. No influence of BK or Hoe140 on the increase in albuminuria induced by Ang
      II was detected. In conclusion, exogenous BK may oppose the effect of Ang II on
      vascular tone, but it cannot prevent hypertension and target-organ damage
      associated with this experimental model of hypertension, even at a very high
      dose.

PMID- 10082496
TI  - Enhancement of bradykinin and resensitization of its B2 receptor.
AB  - We studied the enhancement of the effects of bradykinin B2 receptor agonists by
      agents that react with active centers of angiotensin-converting enzyme (ACE)
      independent of enzymatic inactivation. The potentiation and the desensitization
      and resensitization of B2 receptor were assessed by measuring [3H]arachidonic
      acid release and [Ca2+]i mobilization in Chinese hamster ovary cells transfected
      to express human ACE and B2 receptor, or in endothelial cells with constitutively
      expressed ACE and receptor. Administration of bradykinin or its ACE-resistant
      analogue desensitized the receptor, but it was resensitized (arachidonic acid
      release or [Ca2+]i mobilization) by agents such as enalaprilat (1 micromol/L).
      Enalaprilat was inactive in the absence of ACE expression. La3+ (100 micromol/L)
      inhibited the apparent resensitization, probably by blocking the entry of
      extracellular calcium. Enalaprilat resensitized the receptor via ACE to release
      arachidonic acid by bradykinin at a lower concentration (5 nmol/L) than required
      to mobilize [Ca2+]i (1 micromol/L). Monoclonal antibodies inhibiting the ACE N
      domain active center and polyclonal antiserum potentiated bradykinin. The snake
      venom peptide BPP5a and metabolites of angiotensin and bradykinin (angiotensin-[1
      9], angiotensin-[1-7], bradykinin-[1-8]; 1 micromol/L) enhanced arachidonic acid
      release by bradykinin. Angiotensin-(1-9) and -(1-7) also resensitized the
      receptor. Enalaprilat potentiated the bradykinin effect in cells expressing a
      mutant ACE with a single N-domain active site. Agents that reacted with a single
      active site, on the N-domain or on the C-domain, potentiated bradykinin not by
      blocking its inactivation but by inducing crosstalk between ACE and the receptor.
      Enalaprilat enhanced signaling via ACE by Galphai in lower concentration than by
      Galphaq-coupled receptor.

PMID- 10082497
TI  - Evidence for involvement of the type 1 angiotensin II receptor locus in essential
      hypertension.
AB  - Components of the renin-angiotensin system play an important role in the normal
      regulation of blood pressure. We carried out a comprehensive genetic linkage
      study of the genes involved in the renin-angiotensin cascade in Finnish
      hypertensive twins and their affected siblings. We found no evidence for linkage
      between essential hypertension and the genes coding for renin, angiotensinogen,
      angiotensin-converting enzyme, or kallikrein 1 in the 329 hypertensive
      individuals of 142 families studied. In contrast, two intragenic markers for the
      type 1 angiotensin II receptor (AT1) showed some evidence for linkage in the
      total sample. A closer examination of this gene locus was carried out using
      subgroups of nonobese sibpairs with early onset of hypertension and uniform
      geographical origin. These stratifications yielded suggestive evidence for
      linkage of hypertension to the genetic area containing the AT1 gene, with a
      maximal multipoint logarithm of the odds (LOD) score of 2.9. A genetic
      association study carried out in an independent series of 50 hypertensive cases
      and 122 normotensive controls showed an increase in the frequency of the A1166-
      >C allele of the AT1 gene in the hypertensive individuals. In a novel variant of
      model-free multipoint linkage analysis allowing linkage disequilibrium in the
      calculations, an LOD score of 5.13 was obtained. Sequence analyses of the entire
      coding region and 848 bp of promoter region in the DNA sample on 8 index samples
      did not reveal previously unpublished sequence variations. The data provide
      evidence that a common genetic variant of the AT1 gene locus influences the risk
      of essential hypertension in the Finnish population.

PMID- 10082498
TI  - Angiotensin II receptor blockade in normotensive subjects: A direct comparison of
      three AT1 receptor antagonists.
AB  - Use of angiotensin (Ang) II AT1 receptor antagonists for treatment of
      hypertension is rapidly increasing, yet direct comparisons of the relative
      efficacy of antagonists to block the renin-angiotensin system in humans are
      lacking. In this study, the Ang II receptor blockade induced by the recommended
      starting dose of 3 antagonists was evaluated in normotensive subjects in a double
      blind, placebo-controlled, randomized, 4-way crossover study. At 1-week
      intervals, 12 subjects received a single dose of losartan (50 mg), valsartan (80
      mg), irbesartan (150 mg), or placebo. Blockade of the renin-angiotensin system
      was assessed before and 4, 24, and 30 hours after drug intake by 3 independent
      methods: inhibition of the blood pressure response to exogenous Ang II, in vitro
      Ang II receptor assay, and reactive changes in plasma Ang II levels. At 4 hours,
      losartan blocked 43% of the Ang II-induced systolic blood pressure increase;
      valsartan, 51%; and irbesartan, 88% (P<0.01 between drugs). The effect of each
      drug declined with time. At 24 hours, a residual effect was found with all 3
      drugs, but at 30 hours, only irbesartan induced a marked, significant blockade
      versus placebo. Similar results were obtained when Ang II receptor blockade was
      assessed with an in vitro receptor assay and by the reactive rise in plasma Ang
      II levels. This study thus demonstrates that the first administration of the
      recommended starting dose of irbesartan induces a greater and longer lasting Ang
      II receptor blockade than that of valsartan and losartan in normotensive
      subjects.

PMID- 10082499
TI  - Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on
      cerebral arterioles in rats.
AB  - We examined the effects of an angiotensin-converting enzyme inhibitor,
      perindopril, and a beta-blocker, propranolol, on cerebral arterioles in stroke
      prone spontaneously hypertensive rats (SHRSP). The structure and mechanics of
      cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP
      that were untreated or treated for 3 months with a high (2 mg/kg per day) or a
      low (0.3 mg/kg per day) dose of perindopril or propranolol (250 mg/kg per day)
      alone or in combination with the low dose of perindopril. We measured pressure,
      external diameter, and cross-sectional area of the vessel wall (CSA) in maximally
      dilated (with EDTA) cerebral arterioles. Treatment of SHRSP with the high dose of
      perindopril or the combination of propranolol and the low dose of perindopril
      normalized cerebral arteriolar mean pressure (50+/-1 [mean+/-SEM] and 43+/-2 mm
      Hg vs 50+/-1 mm Hg in WKY and 94+/-3 mm Hg in untreated SHRSP; P<0.05), pulse
      pressure (15+/-1 and 16+/-1 mm Hg vs 13+/-1 mm Hg in WKY and 35+/-1 mm Hg in
      untreated SHRSP; P<0.05), and CSA (1103+/-53 and 1099+/-51 microm2, respectively,
      vs 1057+/-49 microm2 in WKY and 1281+/-62 microm2 in untreated SHRSP; P<0.05). In
      contrast, treatment of SHRSP with the low dose of perindopril or propranolol
      alone did not normalize arteriolar pulse pressure (24+/-1 and 21+/-1 mm Hg) and
      failed to prevent increases in CSA (1282+/-77 and 1267+/-94 microm2). Treatment
      with either dose of perindopril or the combination of propranolol and perindopril
      significantly increased external diameter in cerebral arterioles of SHRSP (99+/
      3, 103+/-2, and 98+/-3 microm vs 87+/-2 microm in untreated SHRSP; P<0.05),
      whereas propranolol alone did not (94+/-3 microm; P>0.05). These findings suggest
      that effects of angiotensin-converting enzyme inhibitors on cerebral arteriolar
      hypertrophy in SHRSP may depend primarily on their effects on arterial pressure,
      particularly pulse pressure, whereas their effects on cerebral arteriolar
      remodeling (defined as a reduction in external diameter) may be pressure
      independent.

PMID- 10082500
TI  - ACE inhibitor versus beta-blocker for the treatment of hypertension in renal
      allograft recipients.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the
      progression of chronic renal failure. However, the value of ACE inhibitors for
      the treatment of hypertension in renal allograft recipients has not been
      established. ACE inhibitors dilate the efferent glomerular arteriole, an effect
      that may aggravate the decrease in glomerular filtration rate resulting from
      cyclosporine-induced vasoconstriction at the afferent glomerular arteriole.
      Therefore, the goal of this double-blind, randomized study was to compare the
      antihypertensive and renal effects of the ACE inhibitor quinapril with those of
      the beta-blocker atenolol in renal allograft recipients in whom hypertension
      developed 6 to 12 weeks after transplantation. All patients received cyclosporine
      as an immunosuppressant and had stable graft function (serum creatinine
      concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who
      received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients
      who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the
      24-month study. The two groups did not differ in age, sex ratio, height, and
      weight before entry into the study. Quinapril decreased diastolic blood pressure
      from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol
      decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum
      creatinine concentration did not change significantly in either group after 24
      months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in
      the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after
      24 months in the atenolol group; P=NS for both groups). After 24 months, the
      change in urinary albumin excretion from baseline was -10+/-15 mg/d in the
      quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results
      show that quinapril and atenolol are effective antihypertensive drugs when used
      after renal transplantation. Moreover, compared with atenolol, quinapril has no
      adverse effects on graft function. The relative reduction in albuminuria observed
      with quinapril as compared with atenolol could indicate a beneficial effect of
      quinapril on long-term graft function.

PMID- 10082501
TI  - Effects of coffee on ambulatory blood pressure in older men and women: A
      randomized controlled trial.
AB  - This study assessed the effects of regular coffee drinking on 24-hour ambulatory
      blood pressure (ABP) in normotensive and hypertensive older men and women. Twenty
      two normotensive and 26 hypertensive, nonsmoking men and women, with a mean age
      of 72.1 years (range, 54 to 89 years), took part in the study. After 2 weeks of a
      caffeine-free diet, subjects were randomized to continue with the caffeine-free
      diet and abstain from caffeine-containing drinks or drink instant coffee (5 cups
      per day, equivalent to 300 mg caffeine per day) in addition to the caffeine-free
      diet for a further 2 weeks. Change in systolic and diastolic blood pressures
      (SBP, DBP) determined by 24-hour ambulatory BP monitoring showed significant
      interactions between coffee drinking and hypertension status. In the hypertensive
      group, rise in mean 24-hour SBP was greater by 4.8 (SEM, 1.3) mm Hg (P=0.031) and
      increase in mean 24-hour DBP was higher by 3.0 (1.0) mm Hg (P=0.010) in coffee
      drinkers than in abstainers. There were no significant differences between
      abstainers and coffee drinkers in the normotensive group for 24-hour, daytime, or
      nighttime SBP or DBP. In older men and women with treated or untreated
      hypertension, ABP increased in coffee drinkers and decreased in abstainers.
      Restriction of coffee intake may be beneficial in older hypertensive individuals.

PMID- 10082502
TI  - Maximum-likelihood generalized heritability estimate for blood pressure in
      Nigerian families.
AB  - Elevated blood pressure (BP) is more common in relatives of hypertensives than in
      relatives of normotensives, indicating familial resemblance of the BP phenotypes.
      Most published studies have been conducted in westernized societies. To assess
      the ability to generalize these estimates, we examined familial patterns of BP in
      a population-based sample of 510 nuclear families, including 1552 individuals
      (320 fathers, 370 mothers, 475 sons, and 387 daughters) from Ibadan, Nigeria. The
      prevalence of obesity in this community is low (body mass index: fathers, 21.6;
      mothers, 23.6; sons, 19.2; and daughters=21.0 kg/m2). The BP phenotype used in
      all analyses was created from the best regression model by standardizing the age
      adjusted systolic blood pressure (SBP) and diastolic blood pressure (DBP) to 0
      mean and unit variance. Heritability was estimated by use of the computer program
      SEGPATH from the most parsimonious model of "no spouse and neither gender nor
      generation difference" as 45% for SBP and 43% for DBP. The lack of a significant
      spouse correlation is consistent with little or no influence of the common
      familial environment. However, the heritability estimate of <50% for both SBP and
      DBPs reinforces the importance of the nonshared environmental effect.

PMID- 10082503
TI  - Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)
      during angiotensin-converting enzyme inhibition in humans.
AB  - We investigated the contributions of angiotensin-converting enzyme (ACE) and
      glomerular filtration to creating the new metabolic balance of the hemoregulatory
      peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute
      and chronic ACE inhibition in healthy subjects. We also studied the effect of
      chronic renal failure on the plasma concentration of AcSDKP during long-term ACE
      inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral
      dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID
      (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold
      (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine
      accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8
      fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE
      activity over time showed an intermittent reactivation of ACE between each
      captopril dose. In subjects with chronic renal failure (creatinine clearance<60
      mL/min per 1.73 m2), plasma AcSDKP levels were 22 times higher (95% confidence
      interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in
      subjects with normal renal function, they were only 4.1 times higher (95%
      confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group
      (n=21). Renal failure itself led to a slight increase in plasma AcSDKP
      concentration. In conclusion, intermittent reactivation of ACE between doses of
      an ACEI is the major mechanism accounting for the lack of major AcSDKP
      accumulation during chronic ACE inhibition in subjects with normal renal
      function.

PMID- 10082504
TI  - Prospective analysis of traits related to 6-year change in sodium-lithium
      countertransport. Gubbio Population Study Research Group.
AB  - Sodium-lithium countertransport (Na-Li CT) activity in red blood cells relates
      cross-sectionally and longitudinally to blood pressure and hypertension.
      Lifestyle and metabolic factors relate cross-sectionally to this sodium
      transporter. The aim of this study was to conduct a prospective analysis of 6
      year Na-Li CT change and of traits related to Na-Li CT change. In 2183
      participants in the Gubbio Population Study (972 men and 1211 women; baseline
      ages, 18 to 74 years), the following data collected at baseline and 6-year follow
      up were analyzed: Na-Li CT; gender; age; body mass index (BMI); blood pressure;
      antihypertensive treatment; alcohol intake; smoking habits; urinary sodium-to
      potassium ratio; and plasma cholesterol, glucose, uric acid, sodium, potassium,
      and triglycerides (measured only at follow-up). Six-year changes were defined as
      follow-up minus baseline values. Na-Li CT was higher at follow-up than at
      baseline in both genders (P<0.001). Baseline Na-Li CT; baseline and change values
      of BMI; and change values of alcohol intake, plasma potassium, and plasma glucose
      related to Na-Li CT change significantly and independently with control for other
      variables. Follow-up plasma triglyceride levels also related independently to Na
      Li CT change. Coefficients were positive for BMI, alcohol intake, and plasma
      glucose and triglyceride levels and were negative for baseline Na-Li CT and
      plasma potassium levels. Baseline and change values of other variables did not
      relate significantly to Na-Li CT change. In conclusion, in prospective analyses,
      BMI, alcohol intake, plasma glucose, and lipids were directly related to Na-Li CT
      change; baseline Na-Li CT and plasma potassium levels were inversely related. The
      data support the concept that lifestyle and related metabolic factors influence
      Na-Li CT.

PMID- 10082505
TI  - Erythropoietin depresses nitric oxide synthase expression by human endothelial
      cells.
AB  - We have recently shown that erythropoietin (EPO)-induced hypertension is
      unrelated to the rise in hematocrit and is marked by elevated cytosolic [Ca+2]
      and nitric oxide (NO) resistance. The present study was done to determine the
      effect of EPO on NO production and endothelial NO synthase (eNOS) expression by
      endothelial cells. Human coronary artery endothelial cells were cultured to
      subconfluence and then were incubated for 24 hours in the presence of either EPO
      (0, 5, and 20 U/mL) alone or EPO plus the calcium channel blocker felodipine. The
      experiments were carried out with quiescent (0.5% FCS) and proliferating (5% FCS)
      cells. Total nitrate and nitrite, eNOS protein, DNA synthesis (thymidine
      incorporation), and cell proliferation (cell count) were determined. In addition,
      NO production in response to acetylcholine stimulation was tested. EPO resulted
      in a dose-dependent inhibition of basal and acetylcholine-stimulated NO
      production and eNOS protein expression and also led to a significant dose
      dependent stimulation of DNA synthesis in endothelial cells. The inhibitory
      effects of EPO on NO production and eNOS expression were reversed by felodipine.
      Thus, EPO downregulates basal and acetylcholine-stimulated NO production,
      depresses eNOS expression, and stimulates proliferation in isolated human
      endothelial cells. The suppressive effects of EPO on NO production and on eNOS
      expression are reversed by calcium channel blockade.

PMID- 10082506
TI  - Human renin mRNA stability is increased in response to cAMP in Calu-6 cells.
AB  - The human carcinoma-derived cell line Calu-6 has previously been demonstrated to
      endogenously express human renin (hREN) mRNA and to markedly increase steady
      state hREN mRNA levels (100-fold after 24 hours) in response to analogues of cAMP
      and postreceptor activators of adenylyl cyclase such as forskolin. However, both
      transfection analysis using hREN promoter-reporter constructs and nuclear run-on
      experiments suggest that transcriptional activity alone cannot account for this
      level of induction. We performed primer extension, reverse transcription
      polymerase chain reaction, and 3' rapid amplification of cDNA ends to compare
      hREN mRNA between unstimulated and forskolin-stimulated cells. We demonstrate
      that hREN mRNA is identical under both conditions with respect to (1) utilization
      of the appropriate transcription start site, (2) processing of renin mRNA, and
      (3) utilization of the proper polyadenylation site and length of the poly-A tail.
      To address the mechanism of induction caused by cAMP, we used transcriptional
      inhibition and measured decay of hREN mRNA before and after forskolin or phorbol
      ester treatment. Experiments with both actinomycin D and 5, 6
      dichlororibofuranosylbenzimidazole (DRB) showed that forskolin treatment markedly
      stabilized hREN mRNA in Calu-6 cells. A 2.3-fold increase in hREN mRNA half-life
      was also observed after treatment of Calu-6 cells with phorbol ester. Experiments
      with DRB demonstrated a similar robust stabilization of hREN mRNA after forskolin
      and phorbol ester treatment. These data demonstrate that the induction in hREN
      mRNA in response to both cAMP and phorbol ester occurs by a mechanism involving a
      posttranscriptional component.

PMID- 10082507
TI  - Protection against necrosis but not apoptosis by heat-stress proteins in vascular
      smooth muscle cells: evidence for distinct modes of cell death.
AB  - We have reported previously that cultured vascular smooth muscle cells (VSMC)
      isolated from spontaneously hypertensive rats (SHR) show higher proliferation and
      cell death than normotensive controls. In addition to protecting cells against
      death, heat stress proteins (HSPs) appear to play a role in cell proliferation.
      This investigation examines the involvement of HSP72 and HSP27 in altered SHR
      VSMC proliferation and death. We have performed detailed discriminatory analysis
      to characterize which type of VSMC death is induced by heat stress (HS) and serum
      deprivation. Serum deprivation induced apoptosis (caspase-3 cleavage and DNA
      laddering) and secondary necrosis, the 2 processes being a continuum of each
      other. In contrast, acute HS (46 degrees C, 30 minutes), which inhibited BN. lx
      and SHR VSMC proliferation by 2-fold, increased necrosis (by 5-fold and 2-fold,
      respectively) but not apoptosis. HSP72 and HSP27 expression evoked in VSMC by
      mild HS (44 degrees C, 15 minutes) 6 hours before acute HS prevented the
      inhibition of proliferation and induction of necrosis with no effect on serum
      deprivation-induced or staurosporine-induced apoptosis. This induced expression
      of HSP72 and HSP27 did not eliminate the higher basal proliferation, apoptosis,
      and necrosis of SHR VSMC compared with BN.lx VSMC, suggesting that these HSPs are
      not involved in altered SHR VSMC proliferation and death. Also, although
      apoptosis and necrosis may be a continuum, in VSMC the 2 processes may be
      distinguished by HS, in which only necrosis is prevented by prior HSP
      accumulation. This observation may be of use in designing strategies for cellular
      protection.

PMID- 10082508
TI  - Cardiovascular effects of nociceptin in unanesthetized mice.
AB  - We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC
      related peptides, including the NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1
      13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus
      intravenous injection of NC decreased mean blood pressure and heart rate. The
      hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more
      prolonged hypotension was evoked by 100 nmol/kg (from 114+/-3 to 97+/-2 mm Hg at
      10 minutes, P<0.01). The latter dose reduced heart rate from 542+/-43 to 479+/-31
      beats/min (P<0.05) and increased aortic blood flow by 41+/-5% (P<0.05).
      Hypotension and bradycardia were also evoked by NC(1-17)NH2 and NC(1-13)NH2
      fragments, whereas NC(1-13)OH and NC(1-9)NH2 were ineffective. Thiorphan, an
      inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by
      NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood
      pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor,
      did not alter basal mean blood pressure or heart rate, but it prevented the
      hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In
      contrast, [F/G]NC(1-13)NH2 did not alter the hypotension induced by bradykinin or
      endomorphin-1 (a micro-receptor agonist), and the bradycardia induced by leu
      enkephalin (a delta-receptor agonist) or U504885 (a synthetic kappa-receptor
      agonist). In conclusion, NC and some of its fragments cause hypotension and
      bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence
      being critical for these biological effects. Our results also demonstrate that
      the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC
      receptor in vivo.

PMID- 10082509
TI  - Mitogen-activated protein kinases: specific messages from ubiquitous messengers.

PMID- 10082510
TI  - Cleavage of eukaryotic translation initiation factor 4G by exogenously added
      hybrid proteins containing poliovirus 2Apro in HeLa cells: effects on gene
      expression.
AB  - Efficient cleavage of both forms of eukaryotic initiation factor 4G (eIF4G-1 and
      eIF4G-2) has been achieved in HeLa cells by incubation with hybrid proteins
      containing poliovirus 2Apro. Entry of these proteins into cells is promoted by
      adenovirus particles. Substantial levels of ongoing translation on preexisting
      cellular mRNAs still continue for several hours after eIF4G degradation.
      Treatment of control HeLa cells with hypertonic medium causes an inhibition of
      translation that is reversed upon restoration of cells to normal medium. Protein
      synthesis is not restored in cells lacking intact eIF4G after hypertonic
      treatment. Notably, induction of synthesis of heat shock proteins still occurs in
      cells pretreated with poliovirus 2Apro, suggesting that transcription and
      translation of these mRNAs takes place even in the presence of cleaved eIF4G.
      Finally, the synthesis of luciferase was examined in a HeLa cell line bearing the
      luciferase gene under control of a tetracycline-regulated promoter. Transcription
      of the luciferase gene and transport of the mRNA to the cytoplasm occurs at
      control levels in eIF4G-deficient cells. However, luciferase synthesis is
      strongly inhibited in these cells. These findings indicate that intact eIF4G is
      necessary for the translation of mRNAs not engaged in translation with the
      exception of heat shock mRNAs but is not necessary for the translation of mRNAs
      that are being translated.

PMID- 10082511
TI  - The J domain of papovaviral large tumor antigen is required for synergistic
      interaction with the POU-domain protein Tst-1/Oct6/SCIP.
AB  - Large T antigens from polyomaviruses are multifunctional proteins with roles in
      transcriptional regulation, viral DNA replication, and cellular transformation.
      They have been shown to enhance the activity of various cellular transcription
      factors. In the case of the POU protein Tst-1/Oct6/SCIP, this enhancement
      involves a direct physical interaction between the POU domain of the
      transcription factor and the amino-terminal region of large T antigen. Here we
      have analyzed the structural requirements for synergistic interaction between the
      two proteins in greater detail. Tst-1/Oct6/SCIP and the related POU protein Brn-1
      were both capable of direct physical interaction with large T antigen.
      Nevertheless, only Tst-1/Oct6/SCIP functioned synergistically with large T
      antigen. This differential behavior was due to differences in the amino-terminal
      regions of the proteins, as evident from chimeras between Tst-1/Oct6/SCIP and Brn
      1. Synergy was specifically observed for constructs containing the amino-terminal
      region of Tst-1/Oct6/SCIP. Large T antigen, on the other hand, functioned
      synergistically with Tst-1/Oct6/SCIP only when the integrity of its J-domain
      containing amino terminus was maintained. Mutations that disrupted the J domain
      concomitantly abolished the ability to enhance the function of Tst-1/Oct6/SCIP.
      The J domain of T antigen was also responsible for the physical interaction with
      Tst-1/Oct6/SCIP and could be replaced in this property by other J domains.
      Intriguingly, a heterologous J domain from a human DnaJ protein partially
      substituted for the amino terminus of T antigen even with regard to the
      synergistic enhancement of Tst-1/Oct6/SCIP function. Given the general role of J
      domains, we propose chaperone activity as the underlying mechanism for synergy
      between Tst-1/Oct6/SCIP and large T antigens.

PMID- 10082512
TI  - Structural and functional analysis of interferon regulatory factor 3:
      localization of the transactivation and autoinhibitory domains.
AB  - The interferon regulatory factor 3 (IRF-3) gene encodes a 55-kDa protein which is
      expressed constitutively in all tissues. In unstimulated cells, IRF-3 is present
      in an inactive cytoplasmic form; following Sendai virus infection, IRF-3 is
      posttranslationally modified by protein phosphorylation at multiple serine and
      threonine residues located in the carboxy terminus. Virus-induced phosphorylation
      of IRF-3 leads to cytoplasmic to nuclear translocation of phosphorylated IRF-3,
      association with the transcriptional coactivator CBP/p300, and stimulation of DNA
      binding and transcriptional activities of virus-inducible genes. Using yeast and
      mammalian one-hybrid analysis, we now demonstrate that an extended, atypical
      transactivation domain is located in the C terminus of IRF-3 between amino acids
      (aa) 134 and 394. We also show that the C-terminal domain of IRF-3 located
      between aa 380 and 427 participates in the autoinhibition of IRF-3 activity via
      an intramolecular association with the N-terminal region between aa 98 and 240.
      After Sendai virus infection, an intermolecular association between IRF-3
      proteins is detected, demonstrating a virus-dependent formation of IRF-3
      homodimers; this interaction is also observed in the absence of virus infection
      with a constitutively activated form of IRF-3. Substitution of the C-terminal Ser
      Thr phosphorylation sites with the phosphomimetic Asp in the region ISNSHPLSLTSDQ
      between amino acids 395 and 407 [IRF-3(5D)], but not the adjacent S385 and S386
      residues, generates a constitutively activated DNA binding form of IRF-3. In
      contrast, substitution of S385 and S386 with either Ala or Asp inhibits both DNA
      binding and transactivation activities of the IRF-3(5D) protein. These studies
      thus define the transactivation domain of IRF-3, two domains that participate in
      the autoinhibition of IRF-3 activity, and the regulatory phosphorylation sites
      controlling IRF-3 dimer formation, DNA binding activity, and association with the
      CBP/p300 coactivator.

PMID- 10082513
TI  - Double-stranded-RNA-activated protein kinase PKR enhances transcriptional
      activation by tumor suppressor p53.
AB  - The tumor suppressor p53 plays a key role in inducing G1 arrest and apoptosis
      following DNA damage. The double-stranded-RNA-activated protein PKR is a
      serine/threonine interferon (IFN)-inducible kinase which plays an important role
      in regulation of gene expression at both transcriptional and translational
      levels. Since a cross talk between IFN-inducible proteins and p53 had already
      been established, we investigated whether and how p53 function was modulated by
      PKR. We analyzed p53 function in several cell lines derived from PKR+/+ and PKR-/
      mouse embryonic fibroblasts (MEFs) after transfection with the temperature
      sensitive (ts) mutant of mouse p53 [p53(Val135)]. Here we report that
      transactivation of transcription by p53 and G0/G1 arrest were impaired in PKR-/-
      cells upon conditions that ts p53 acquired a wild-type conformation.
      Phosphorylation of mouse p53 on Ser18 was defective in PKR-/- cells, consistent
      with an impaired transcriptional induction of the p53-inducible genes encoding
      p21(WAF/Cip1) and Mdm2. In addition, Ser18 phosphorylation and transcriptional
      activation by mouse p53 were diminished in PKR-/- cells after DNA damage induced
      by the anticancer drug adriamycin or gamma radiation but not by UV radiation.
      Furthermore, the specific phosphatidylinositol-3 (PI-3) kinase inhibitor LY294002
      inhibited the induction of phosphorylation of Ser18 of p53 by adriamycin to a
      higher degree in PKR+/+ cells than in PKR-/- cells. These novel findings suggest
      that PKR enhances p53 transcriptional function and implicate PKR in cell
      signaling elicited by a specific type of DNA damage that leads to p53
      phosphorylation, possibly through a PI-3 kinase pathway.

PMID- 10082514
TI  - p70(S6K) controls selective mRNA translation during oocyte maturation and early
      embryogenesis in Xenopus laevis.
AB  - In mammalian cells, p70(S6K) plays a key role in translational control of cell
      proliferation in response to growth factors. Because of the reliance on
      translational control in early vertebrate development, we cloned a Xenopus
      homolog of p70(S6K) and investigated the activity profile of p70(S6K) during
      Xenopus oocyte maturation and early embryogenesis. p70(S6K) activity is high in
      resting oocytes and decreases to background levels upon stimulation of maturation
      with progesterone. During embryonic development, three peaks of activity were
      observed: immediately after fertilization, shortly before the midblastula
      transition, and during gastrulation. Rapamycin, an inhibitor of p70(S6K)
      activation, caused oocytes to undergo germinal vesicle breakdown earlier than
      control oocytes, and sensitivity to progesterone was increased. Injection of a
      rapamycin-insensitive, constitutively active mutant of p70(S6K) reversed the
      effects of rapamycin. However, increases in S6 phosphorylation were not
      significantly affected by rapamycin during maturation. mos mRNA, which does not
      contain a 5'-terminal oligopyrimidine tract (5'-TOP), was translated earlier, and
      a larger amount of Mos protein was produced in rapamycin-treated oocytes. In
      fertilized eggs rapamycin treatment increased the translation of the Cdc25A
      phosphatase, which lacks a 5'-TOP. Translation assays in vivo using both DNA and
      RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased
      translational activity with rapamycin, whereas constructs without a 5'-TOP or
      with an internal ribosome entry site were translated more efficiently upon
      rapamycin treatment. These results suggest that changes in p70(S6K) activity
      during oocyte maturation and early embryogenesis selectively alter the
      translational capacity available for mRNAs lacking a 5'-TOP region.

PMID- 10082515
TI  - Targeted disruption of Smad3 reveals an essential role in transforming growth
      factor beta-mediated signal transduction.
AB  - The Smads are a family of nine related proteins which function as signaling
      intermediates for the transforming growth factor beta (TGF-beta) superfamily of
      ligands. To discern the in vivo functions of one of these Smads, Smad3, we
      generated mice harboring a targeted disruption of this gene. Smad3 null mice,
      although smaller than wild-type littermates, are viable, survive to adulthood,
      and exhibit an early phenotype of forelimb malformation. To study the cellular
      functions of Smad3, we generated Smad3 null mouse embryonic fibroblasts (MEFs)
      and dermal fibroblasts. We demonstrate that null MEFs have lost the ability to
      form Smad-containing DNA binding complexes and are unable to induce transcription
      from the TGF-beta-responsive promoter construct, p3TP-lux. Using the primary
      dermal fibroblasts, we also demonstrate that Smad3 is integral for induction of
      endogenous plasminogen activator inhibitor 1. We subsequently demonstrate that
      Smad3 null MEFs are partially resistant to TGF-beta's antiproliferative effect,
      thus firmly establishing a role for Smad3 in TGF-beta-mediated growth inhibition.
      We next examined cells in which Smad3 is most highly expressed, specifically
      cells of immune origin. Although no specific developmental defect was detected in
      the immune system of the Smad3 null mice, a functional defect was observed in the
      ability of TGF-beta to inhibit the proliferation of splenocytes activated by
      specific stimuli. In addition, primary splenocytes display defects in TGF-beta
      mediated repression of cytokine production. These data, taken together, establish
      a role for Smad3 in mediating the antiproliferative effects of TGF-beta and
      implicate Smad3 as a potential effector for TGF-beta in modulating immune system
      function.

PMID- 10082516
TI  - Requirement of RBP9, a Drosophila Hu homolog, for regulation of cystocyte
      differentiation and oocyte determination during oogenesis.
AB  - The Drosophila RNA binding protein RBP9 and its Drosophila and human homologs,
      ELAV and the Hu family of proteins, respectively, are highly expressed in the
      nuclei of neuronal cells. However, biochemical studies suggest that the Hu
      proteins function in the regulation of mRNA stability, which occurs in the
      cytoplasm. In this paper, we show that RBP9 is expressed not only in the nuclei
      of neuronal cells but also in the cytoplasm of cystocytes during oogenesis.
      Despite the predominant expression of RBP9 in nerve cells, mutational analysis
      revealed a female sterility phenotype rather than neuronal defects for Rbp9
      mutants. The female sterility phenotype of the Rbp9 mutants resulted from defects
      in oogenesis; the lack of Rbp9 activity caused the germarium region of the
      mutants to be filled with undifferentiated cystocytes. RBP9 appears to stimulate
      cystocyte differentiation by regulating the expression of bag-of-marbles (bam)
      mRNA, which encodes a developmental regulator of germ cells. RBP9 protein bound
      specifically to bam mRNA in vitro, which is required for cystocyte proliferation,
      and the number of cells that expressed BAM protein was increased 5- to 10-fold in
      the germarium regions of Rbp9 mutants. These results suggest that RBP9 protein
      binds to bam mRNA to down regulate BAM protein expression, which is essential for
      the initiation of cystocyte differentiation into functional egg chambers. In
      hypomorphic Rbp9 mutants, cystocytes differentiated into egg chambers; however,
      oocyte determination and positioning were perturbed. Therefore, the concentrated
      localization of RBP9 protein in the oocyte of the early egg chambers may be
      required for proper oocyte determination or positioning.

PMID- 10082517
TI  - Esa1p is an essential histone acetyltransferase required for cell cycle
      progression.
AB  - Histones are dynamically modified during chromatin assembly, as specific
      transcriptional patterns are established, and during mitosis and development.
      Modifications include acetylation, phosphorylation, ubiquitination, methylation,
      and ADP-ribosylation, but the biological significance of each of these is not
      well understood. For example, distinct acetylation patterns correlate with
      nucleosome formation and with transcriptionally activated or silenced chromatin,
      yet mutations in genes encoding several yeast histone acetyltransferase (HAT)
      activities result in either no cellular phenotype or only modest growth defects.
      Here we report characterization of ESA1, an essential gene that is a member of
      the MYST family that includes two yeast silencing genes, human genes associated
      with leukemia and with the human immunodeficiency virus type 1 Tat protein, and
      Drosophila mof, a gene essential for male dosage compensation. Esa1p acetylates
      histones in a pattern distinct from those of other yeast enzymes, and temperature
      sensitive mutant alleles abolish enzymatic activity in vitro and result in
      partial loss of an acetylated isoform of histone H4 in vivo. Strains carrying
      these mutations are also blocked in the cell cycle such that at restrictive
      temperatures, esa1 mutants succeed in replicating their DNA but fail to proceed
      normally through mitosis and cytokinesis. Recent studies show that Esa1p enhances
      transcription in vitro and thus may modulate expression of genes important for
      cell cycle control. These observations therefore link an essential HAT activity
      to cell cycle progression, potentially through discrete transcriptional
      regulatory events.

PMID- 10082518
TI  - The yeast C-type cyclin Ctk2p is phosphorylated and rapidly degraded by the
      ubiquitin-proteasome pathway.
AB  - The yeast CTDK-I complex has been implicated in phosphorylation of the carboxy
      terminal domain of the RNA polymerase II and in transcription control. It is
      composed of three polypeptides: Ctk1p and Ctk2p, a cyclin-dependent kinase and a
      C-type cyclin subunit, respectively; and Ctk3p, a third subunit of unknown
      function. Cyclins are regulatory proteins whose expression is tightly controlled
      at the protein level. In this study, we examined the regulation of Ctk2p
      expression in vivo. Surprisingly, unlike what has been described for cell cycle
      cyclins, steady-state levels of Ctk2p are composed of two relatively abundant
      forms, one of them phosphorylated. We show that this phosphorylated form is
      extremely unstable (half-life, 5 min) and that rapid proteolysis of Ctk2p
      exhibits growth-related regulation. Furthermore, our data establish that similar
      to the case for other naturally short-lived proteins, Ctk2p degradation is
      mediated by the ubiquitin-proteasome pathway. This is the first demonstration
      that a C-type cyclin is phosphorylated and targeted to the proteasome.
      Strikingly, neither phosphorylation nor destruction of Ctk2p requires its
      associated kinase Ctk1p, a feature fundamentally different from that which has
      been observed for cell cycle cyclins.

PMID- 10082519
TI  - The schizosaccharomyces pombe dim1(+) gene interacts with the anaphase-promoting
      complex or cyclosome (APC/C) component lid1(+) and is required for APC/C
      function.
AB  - The Schizosaccharomyces pombe dim1(+) gene is required for entry into mitosis and
      for chromosome segregation during mitosis. To further understand dim1p function,
      we undertook a synthetic lethal screen with the temperature-sensitive dim1-35
      mutant and isolated lid (for lethal in dim1-35) mutants. Here, we describe the
      temperature-sensitive lid1-6 mutant. At the restrictive temperature of 36 degrees
      C, lid1-6 mutant cells arrest with a "cut" phenotype similar to that of cut4 and
      cut9 mutants. An epitope-tagged version of lid1p is a component of a multiprotein
      approximately 20S complex; the presence of lid1p in this complex depends upon
      functional cut9(+). lid1p-myc coimmunoprecipitates with several other proteins,
      including cut9p and nuc2p, and the presence of cut9p in a 20S complex depends
      upon the activity of lid1(+). Further, lid1(+) function is required for the
      multiubiquitination of cut2p, an anaphase-promoting complex or cyclosome (APC/C)
      target. Thus, lid1p is a component of the S. pombe APC/C. In dim1 mutants, the
      abundances of lid1p and the APC/C complex decline significantly, and the
      ubiquitination of an APC/C target is abolished. These data suggest that at least
      one role of dim1p is to maintain or establish the steady-state level of the
      APC/C.

PMID- 10082520
TI  - Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its
      dephosphorylation: a novel pathway controlled by HSP72.
AB  - Various stresses activate the c-Jun N-terminal kinase (JNK), which is involved in
      the regulation of many aspects of cellular physiology, including apoptosis. Here
      we demonstrate that in contrast to UV irradiation, heat shock causes little or no
      stimulation of the JNK-activating kinase SEK1, while knocking out the SEK1 gene
      completely blocks heat-induced JNK activation. Therefore, we tested whether heat
      shock activates JNK via inhibition of JNK dephosphorylation. The rate of JNK
      dephosphorylation in unstimulated cells was high, and exposure to UV irradiation,
      osmotic shock, interleukin-1, or anisomycin did not affect this process.
      Conversely, exposure of cells to heat shock and other protein-damaging
      conditions, including ethanol, arsenite, and oxidative stress, strongly reduced
      the rate of JNK dephosphorylation. Under these conditions, we did not observe any
      effects on dephosphorylation of the homologous p38 kinase, suggesting that
      suppression of dephosphorylation is specific to JNK. Together, these data
      indicate that activation of JNK by protein-damaging treatments is mediated
      primarily by inhibition of a JNK phosphatase(s). Elevation of cellular levels of
      the major heat shock protein Hsp72 inhibited a repression of JNK
      dephosphorylation by these stressful treatments, which explains recent reports of
      the suppression of JNK activation by Hsp72.

PMID- 10082521
TI  - Parental allele-specific chromatin configuration in a boundary-imprinting-control
      element upstream of the mouse H19 gene.
AB  - The mouse H19 gene is expressed from the maternal chromosome exclusively. A 2-kb
      region at 2 to 4 kb upstream of H19 is paternally methylated throughout
      development, and these sequences are necessary for the imprinted expression of
      both H19 and the 5'-neighboring Igf2 gene. In particular, on the maternal
      chromosome this element appears to insulate the Igf2 gene from enhancers located
      downstream of H19. We analyzed the chromatin organization of this element by
      assaying its sensitivity to nucleases in nuclei. Six DNase I hypersensitive sites
      (HS sites) were detected on the unmethylated maternal chromosome exclusively, the
      two most prominent of which mapped 2.25 and 2.75 kb 5' to the H19 transcription
      initiation site. Five of the maternal HS sites were present in expressing and
      nonexpressing tissues and in embryonic stem (ES) cells. They seem, therefore, to
      reflect the maternal origin of the chromosome rather than the expression of H19.
      A sixth maternal HS site, at 3.45 kb upstream of H19, was detected in ES cells
      only. The nucleosomal organization of this element was analyzed in tissues and ES
      cells by micrococcal nuclease digestion. Specifically on the maternal chromosome,
      an unusual and strong banding pattern was obtained, suggestive of a
      nonnucleosomal organization. From our studies, it appears that the unusual
      chromatin organization with the presence of HS sites (maternal chromosome) and
      DNA methylation (paternal chromosome) in this element are mutually exclusive and
      reflect alternate epigenetic states. In addition, our data suggest that
      nonhistone proteins are associated with the maternal chromosome and that these
      might be involved in its boundary function.

PMID- 10082522
TI  - Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with
      Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription.
AB  - Pituitary gonadotropins are critical regulators of gonadal development and
      function. Expression and secretion of the mature hormones are regulated by
      gonadotropin-releasing hormone (GnRH), which is itself secreted from the
      hypothalamus. GnRH stimulation of gonadotropin expression and secretion occurs
      through the G-protein-linked phospholipase C/inositol triphosphate intracellular
      signaling pathway, which ultimately leads to protein kinase C (PKC) activation
      and increased intracellular calcium levels. Transcription factors mediating the
      effects of GnRH-induced signals on transcription of gonadotropin genes have not
      yet been identified. Recent studies have identified key factors involved in
      luteinizing hormone beta (LHbeta) gonadotropin gene transcription: the nuclear
      receptor SF-1, the bicoid-related homeoprotein Ptx1 (Pitx1), and the immediate
      early Egr-1 gene. We now show that GnRH is a potent stimulator of Egr-1, but not
      Ptx1 or SF-1, expression. Further, Egr-1 activation of the LHbeta promoter is
      specifically enhanced by PKC, in agreement with a role for Egr-1 in mediating a
      GnRH effect on transcription. Egr-1 interacts directly with Ptx1 and with SF-1,
      leading to an enhancement of Ptx1- and SF-1-induced LHbeta transcription. Thus,
      Egr-1 is a likely transcriptional mediator of GnRH-induced signals for activation
      of the LHbeta gene.

PMID- 10082523
TI  - Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a
      multiprotein transcriptional complex required for activity of the human cardiac
      alpha-actin promoter.
AB  - Activation of the human cardiac alpha-actin (HCA) promoter in skeletal muscle
      cells requires the integrity of DNA binding sites for the serum response factor
      (SRF), Sp1, and the myogenic basic helix-loop-helix (bHLH) family. In this study
      we report that activation of the HCA correlates with formation of a muscle
      specific multiprotein complex on the promoter. We provide evidence that proteins
      eluted from the multiprotein complex specifically react with antibodies directed
      against myogenin, Sp1, and SRF and that the complex can be assembled in vitro by
      using the HCA promoter and purified MyoD, E12, SRF, and Sp1. In vitro and in vivo
      assays revealed a direct association of Sp1 and myogenin-MyoD mediated by the DNA
      binding domain of Sp1 and the HLH motif of myogenin. The results obtained in this
      study indicate that protein-protein interactions and the cooperative DNA binding
      of transcriptional activators are critical steps in the formation of a
      transcriptionally productive multiprotein complex on the HCA promoter and suggest
      that the same mechanisms might be utilized to regulate the transcription of
      muscle-specific and other genes.

PMID- 10082524
TI  - Ku-dependent nonhomologous DNA end joining in Xenopus egg extracts.
AB  - An extract from activated Xenopus eggs joins both matching and nonmatching ends
      of exogenous linear DNA substrates with high efficiency and fidelity (P. Pfeiffer
      and W. Vielmetter, Nucleic Acids Res. 16:907-924, 1988). In mammalian cells, such
      nonhomologous end joining (NHEJ) is known to require the Ku heterodimer, a
      component of DNA-dependent protein kinase. Here I investigated whether Ku is also
      required for the in vitro reaction in the egg extract. Immunological assays
      indicate that Ku is very abundant in the extract. I found that all NHEJ was
      inhibited by autoantibodies against Ku and that NHEJ between certain combinations
      of DNA ends was also decreased after immunodepletion of Ku from the extract. The
      formation of a joint between a DNA end with a 5'-protruding single strand (PSS)
      and an end with a 3'-PSS, between two ends with 3'-PSS, and between two blunt
      ends was most Ku dependent. On the other hand, NHEJ between two DNA ends bearing
      5'-PSS was Ku independent. These results show that the Xenopus cell-free system
      will be useful to biochemically dissect the role of Ku in eukaryotic NHEJ.

PMID- 10082525
TI  - The c-fos proto-oncogene is a target for transactivation by the p53 tumor
      suppressor.
AB  - The p53 tumor suppressor gene is mutated in over 50% of human cancers, resulting
      in inactivation of the wild-type (wt) p53 protein. The most notable biochemical
      feature of p53 is its ability to act as a sequence-specific transcriptional
      activator. Through use of the suppression subtractive hybridization differential
      screening technique, we identified c-fos as a target for transcriptional
      stimulation by p53 in cells undergoing p53-mediated apoptosis. Overexpression of
      wt p53 induces c-fos mRNA and protein. Moreover, in vivo induction of c-fos in
      the thymus following whole-body exposure to ionizing radiation is p53 dependent.
      p53 responsiveness does not reside in the basal c-fos promoter. Rather, a
      distinct region within the c-fos gene first intron binds specifically to p53 and
      confers upon the c-fos promoter the ability to become transcriptionally activated
      by wt p53. Identification of c-fos as a specific target for transcriptional
      activation by p53 establishes a direct link between these two pivotal regulatory
      proteins and raises the possibility that c-fos contributes to some of the
      biological effects of p53.

PMID- 10082526
TI  - Distinct factors regulate the murine RAG-2 promoter in B- and T-cell lines.
AB  - The recombination activating genes RAG-1 and RAG-2 are expressed in a lymphoid
      cell-specific and developmentally regulated fashion. To understand the
      transcriptional basis for this regulation, we have cloned and characterized the
      murine RAG-2 promoter. The promoter was lymphoid cell specific, showing activity
      in various B- and T-cell lines but little activity in nonlymphoid cells. To our
      surprise, however, the promoter was regulated differently in B and T cells. Using
      nuclear extracts from B-cell lines, we found that the B-cell-specific
      transcription factor BSAP (Pax-5) could bind to a conserved sequence critical for
      promoter activity. BSAP activated the promoter in transfected cells, and the BSAP
      site was occupied in a tissue-specific manner in vivo. An overlapping DNA
      sequence binding to a distinct factor was necessary for promoter activity in T
      cells. Full promoter activity in T cells was also dependent on a more distal DNA
      sequence whose disruption had no effect on B-cell activity. The unexpected
      finding that a B-cell-specific factor regulates the RAG-2 promoter may explain
      some of the recently observed differences in the regulation of RAG transcription
      between B and T cells.

PMID- 10082527
TI  - Multiple layers of cooperativity regulate enhanceosome-responsive RNA polymerase
      II transcription complex assembly.
AB  - Two coordinate forms of transcriptional synergy mediate eukaryotic gene
      regulation: the greater-than-additive transcriptional response to multiple
      promoter-bound activators, and the sigmoidal response to increasing activator
      concentration. The mechanism underlying the sigmoidal response has not been
      elucidated but is almost certainly founded on the cooperative binding of
      activators and the general machinery to DNA. Here we explore that mechanism by
      using highly purified transcription factor preparations and a strong Epstein-Barr
      virus promoter, BHLF-1, regulated by the virally encoded activator ZEBRA. We
      demonstrate that two layers of cooperative binding govern transcription complex
      assembly. First, the architectural proteins HMG-1 and -2 mediate cooperative
      formation of an enhanceosome containing ZEBRA and cellular Sp1. This enhanceosome
      then recruits transcription factor IIA (TFIIA) and TFIID to the promoter to form
      the DA complex. The DA complex, however, stimulates assembly of the enhanceosome
      itself such that the entire reaction can occur in a highly concerted manner. The
      data reveal the importance of reciprocal cooperative interactions among
      activators and the general machinery in eukaryotic gene regulation.

PMID- 10082528
TI  - The Ets2 transcription factor inhibits apoptosis induced by colony-stimulating
      factor 1 deprivation of macrophages through a Bcl-xL-dependent mechanism.
AB  - Bcl-xL, a member of the Bcl-2 family, inhibits apoptosis, and its expression is
      regulated at the transcriptional level, yet nothing is known about the
      transcription factors specifically activating this promoter. The bcl-x promoter
      contains potential Ets binding sites, and we show that the transcription factor,
      Ets2, first identified by its sequence identity to v-ets of the E26 retrovirus,
      can transactivate the bcl-x promoter. Transient expression of Ets2 results in the
      upregulation of Bcl-xL but not of Bcl-xS, an alternatively spliced gene product
      which induces apoptosis. Ets2 is ubiquitously expressed at low levels in a
      variety of cell types and tissues but is specifically induced to abundant levels
      during macrophage differentiation. Since Bcl-xL is also upregulated during
      macrophage differentiation, we asked whether the bcl-x could be a direct
      downstream target gene of Ets2 in macrophages. BAC1.2F5 macrophages, which are
      dependent on macrophage colony-stimulating factor 1 (CSF-1) for their growth and
      survival, were used in these studies. We show that CSF-1 stimulation of BAC1.2F5
      macrophages results in the upregulation of expression of ets2 and bcl-xL with
      similar kinetics of induction. In the absence of CSF-1, these macrophages undergo
      cell death by apoptosis, whereas constitutive expression of Ets2 rescues these
      cells from cell death, and bcl-xL is upregulated. These results strongly suggest
      a novel role of Ets2 in affecting apoptosis through its regulation of Bcl-xL
      transcription.

PMID- 10082529
TI  - Synergism with germ line transcription factor Oct-4: viral oncoproteins share the
      ability to mimic a stem cell-specific activity.
AB  - Activation of transcription by Oct-4 from remote binding sites requires a
      cofactor that is restricted to embryonal stem cells. The adenovirus E1A protein
      can mimic the activity of this stem cell-specific factor and stimulates Oct-4
      activity in differentiated cells. Here we characterize the Oct-4-E1A interaction
      and show that the E1A 289R protein harbors two independent Oct-4 binding sites,
      both of which specifically interact with the POU domain of Oct-4. Furthermore, we
      demonstrate that, like E1A, the human papillomavirus E7 oncoprotein also
      specifically binds to the Oct-4 POU domain. E7 and Oct-4 can form a complex both
      in vitro and in vivo. Expression of E7 in differentiated cells stimulates Oct-4
      mediated transactivation from distal binding sites. Moreover, Oct-4, but not
      other Oct factors, is active when expressed in cells transformed by human
      papillomavirus. Our results suggest that different viruses have evolved
      oncoproteins that share the ability to target Oct-4 and to mimic a stem cell
      specific activity.

PMID- 10082530
TI  - Inhibition of nuclear receptor signalling by poly(ADP-ribose) polymerase.
AB  - Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated
      protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP
      ribose units from NAD+ to nuclear proteins that are located within chromatin. We
      report here the identification of a novel property of PARP as a modulator of
      nuclear receptor signalling. PARP bound directly to retinoid X receptors (RXR)
      and repressed ligand-dependent transcriptional activities mediated by
      heterodimers of RXR and thyroid hormone receptor (TR). The interacting surface is
      located in the DNA binding domain of RXRalpha. Gel shift assays demonstrated that
      PARP bound to TR-RXR heterodimers on the response element. Overexpression of wild
      type PARP selectively blocked nuclear receptor function in transient transfection
      experiments, while enzyme-defective mutant PARP did not show significant
      inhibition, suggesting that the essential role of poly(ADP-ribosyl) enzymatic
      activity is in gene regulation by nuclear receptors. Furthermore, PARP fused to
      the Gal4 DNA binding domain suppressed the transcriptional activity of the
      promoter harboring the Gal4 binding site. Thus, PARP has transcriptional
      repressor activity when recruited to the promoter. These results indicates that
      poly(ADP-ribosyl)ation is a negative cofactor in gene transcription, regulating a
      member of the nuclear receptor superfamily.

PMID- 10082531
TI  - Differential protein S-thiolation of glyceraldehyde-3-phosphate dehydrogenase
      isoenzymes influences sensitivity to oxidative stress.
AB  - The irreversible oxidation of cysteine residues can be prevented by protein S
      thiolation, in which protein -SH groups form mixed disulfides with low-molecular
      weight thiols such as glutathione. We report here the identification of
      glyceraldehyde-3-phosphate dehydrogenase as the major target of protein S
      thiolation following treatment with hydrogen peroxide in the yeast Saccharomyces
      cerevisiae. Our studies reveal that this process is tightly regulated, since,
      surprisingly, despite a high degree of sequence homology (98% similarity and 96%
      identity), the Tdh3 but not the Tdh2 isoenzyme was S-thiolated. The
      glyceraldehyde-3-phosphate dehydrogenase enzyme activity of both the Tdh2 and
      Tdh3 isoenzymes was decreased following exposure to H2O2, but only Tdh3 activity
      was restored within a 2-h recovery period. This indicates that the inhibition of
      the S-thiolated Tdh3 polypeptide was readily reversible. Moreover, mutants
      lacking TDH3 were sensitive to a challenge with a lethal dose of H2O2, indicating
      that the S-thiolated Tdh3 polypeptide is required for survival during conditions
      of oxidative stress. In contrast, a requirement for the nonthiolated Tdh2
      polypeptide was found during exposure to continuous low levels of oxidants,
      conditions where the Tdh3 polypeptide would be S-thiolated and hence inactivated.
      We propose a model in which both enzymes are required during conditions of
      oxidative stress but play complementary roles depending on their ability to
      undergo S-thiolation.

PMID- 10082532
TI  - Regulation of fibronectin EDA exon alternative splicing: possible role of RNA
      secondary structure for enhancer display.
AB  - The fibronectin primary transcript undergoes alternative splicing in three
      noncoordinated sites: the cassette-type EDA and EDB exons and the more complex
      IIICS region. We have shown previously that an 81-nucleotide region within the
      EDA exon is necessary for exon recognition and that this region contains at least
      two splicing-regulatory elements: a polypurinic enhancer (exonic splicing
      enhancer [ESE]) and a nearby silencer element (exonic splicing silencer [ESS]).
      Here, we have analyzed the function of both elements in different cell types. We
      have mapped the ESS to the nucleotide level, showing that a single base change is
      sufficient to abolish its function. Testing of the ESE and ESS elements in
      heterologous exons, individually or as part of the complete EDA regulatory
      region, showed that only the ESE element is active in different contexts.
      Functional studies coupled to secondary-structure enzymatic analysis of the EDA
      exon sequence variants suggest that the role of the ESS element may be
      exclusively to ensure the proper RNA conformation and raise the possibility that
      the display of the ESE element in a loop position may represent a significant
      feature of the exon splicing-regulatory region.

PMID- 10082533
TI  - Rpb7 can interact with RNA polymerase II and support transcription during some
      stresses independently of Rpb4.
AB  - Rpb4 and Rpb7 are two yeast RNA polymerase II (Pol II) subunits whose mechanistic
      roles have recently started to be deciphered. Although previous data suggest that
      Rpb7 can stably interact with Pol II only as a heterodimer with Rpb4, RPB7 is
      essential for viability, whereas RPB4 is essential only during some stress
      conditions. To resolve this discrepancy and to gain a better understanding of the
      mode of action of Rpb4, we took advantage of the inability of cells lacking RPB4
      (rpb4Delta, containing Pol IIDelta4) to grow above 30 degrees C and screened for
      genes whose overexpression could suppress this defect. We thus discovered that
      overexpression of RPB7 could suppress the inability of rpb4Delta cells to grow at
      34 degrees C (a relatively mild temperature stress) but not at higher
      temperatures. Overexpression of RPB7 could also partially suppress the cold
      sensitivity of rpb4Delta strains and fully suppress their inability to survive a
      long starvation period (stationary phase). Notably, however, overexpression of
      RPB4 could not override the requirement for RPB7. Consistent with the growth
      phenotype, overexpression of RPB7 could suppress the transcriptional defect
      characteristic of rpb4Delta cells during the mild, but not during a more severe,
      heat shock. We also demonstrated, through two reciprocal coimmunoprecipitation
      experiments, a stable interaction of the overproduced Rpb7 with Pol IIDelta4.
      Nevertheless, fewer Rpb7 molecules interacted with Pol IIDelta4 than with wild
      type Pol II. Thus, a major role of Rpb4 is to augment the interaction of Rpb7
      with Pol II. We suggest that Pol IIDelta4 contains a small amount of Rpb7 that is
      sufficient to support transcription only under nonstress conditions. When RPB7 is
      overexpressed, more Rpb7 assembles with Pol IIDelta4, enough to permit
      appropriate transcription also under some stress conditions.

PMID- 10082534
TI  - Interleukin-2 (IL-2) regulates the accessibility of the IL-2-responsive enhancer
      in the IL-2 receptor alpha gene to transcription factors.
AB  - Interleukin-2 (IL-2) responsiveness of T lymphocytes is controlled through
      transcription of the IL-2 receptor (IL-2R) alpha subunit by antigen and by IL-2
      itself. IL-2 induces IL-2Ralpha transcription via an IL-2-responsive enhancer (IL
      2rE), whose activity depends on the cooperative binding of IL-2-induced STAT5 to
      two sites and of constitutively active Elf-1 to a third one. Here we describe the
      changes in IL-2rE chromatin that occur in normal T lymphocytes upon activation of
      IL-2Ralpha expression. In cells induced to transiently express IL-2Ralpha with
      concanavalin A (which mimics antigen), none of the IL-2rE sites is occupied
      despite the presence of Elf-1 and STAT1, which bind to the IL-2rE in vitro. The
      two STAT binding sites are occupied rapidly upon IL-2 stimulation, concomitantly
      with STAT5 activation. Occupation of the Elf-1 binding site is delayed, although
      Elf-1 concentration and binding activity are not modified by IL-2. Digestion of T
      cell chromatin with DNase I and micrococcal nuclease shows that IL-2 induces the
      appearance of nuclease-hypersensitive sites flanking the IL-2rE. Thus IL-2, in
      addition to activating STAT5, appears to regulate IL-2Ralpha transcription by
      making IL-2Ralpha chromatin accessible to transcription factors.

PMID- 10082535
TI  - NF-kappaB function in growth control: regulation of cyclin D1 expression and
      G0/G1-to-S-phase transition.
AB  - Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell
      proliferation, transformation, and tumor development. We provide evidence for a
      direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was
      found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint
      control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred
      activation by NF-kappaB as well as by growth factors. Both levels and kinetics of
      cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover,
      inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1
      associated kinase activity and resulted in delayed phosphorylation of the
      retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition
      in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell
      cycle progression of T47D cells expressing an NF-kappaB superrepressor
      (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus,
      NF-kappaB contributes to cell cycle progression, and one of its targets might be
      cyclin D1.

PMID- 10082536
TI  - Polypyrimidine tract binding protein functions as a repressor to regulate
      alternative splicing of alpha-actinin mutally exclusive exons.
AB  - The smooth muscle (SM) and nonmuscle (NM) isoforms of alpha-actinin are produced
      by mutually exclusive splicing of an upstream NM exon and a downstream SM
      specific exon. A rat alpha-actinin genomic clone encompassing the mutually
      exclusive exons was isolated and sequenced. The SM exon was found to utilize two
      branch points located 382 and 386 nucleotides (nt) upstream of the 3' splice
      site, while the NM exon used a single branch point 191 nt upstream. Mutually
      exclusive splicing arises from the proximity of the SM branch points to the NM 5'
      splice site, and this steric repression could be relieved in part by the
      insertion of spacer elements. In addition, the SM exon is repressed in non-SM
      cells and extracts. In vitro splicing of spacer-containing transcripts could be
      activated by (i) truncation of the transcript between the SM polypyrimidine tract
      and exon, (ii) addition of competitor RNAs containing the 3' end of the actinin
      intron or regulatory sequences from alpha-tropomyosin (TM), and (iii) depletion
      of the splicing extract by using biotinylated alpha-TM RNAs. A number of lines of
      evidence point to polypyrimidine tract binding protein (PTB) as the trans-acting
      factor responsible for repression. PTB was the only nuclear protein observed to
      cross-link to the actinin RNA, and the ability of various competitor RNAs to
      activate splicing correlated with their ability to bind PTB. Furthermore,
      repression of alpha-actinin splicing in the nuclear extracts depleted of PTB by
      using biotinylated RNA could be specifically restored by the addition of
      recombinant PTB. Thus, alpha-actinin mutually exclusive splicing is enforced by
      the unusual location of the SM branch point, while constitutive repression of the
      SM exon is conferred by regulatory elements between the branch point and 3'
      splice site and by PTB.

PMID- 10082537
TI  - Reciprocal interaction between two cellular proteins, Puralpha and YB-1,
      modulates transcriptional activity of JCVCY in glial cells.
AB  - Cross communication between regulatory proteins is an important event in the
      control of eukaryotic gene transcription. Here we have examined the structural
      and functional interaction between two cellular regulatory proteins, YB-1 and
      Puralpha, on the 23-bp sequence element derived from the enhancer-promoter of the
      human polyomavirus JCV. YB-1 and Puralpha are single-stranded DNA binding
      proteins which recognize C/T- and GC/GA-rich sequences, respectively. Results
      from band shift studies demonstrated that while both proteins interact directly
      with their DNA target sequences within the 23-bp motif, each protein can regulate
      the association of the other one with the DNA. Affinity chromatography and
      coimmunoprecipitation provide evidence for a direct interaction between Puralpha
      and YB-1 in the absence of the DNA sequence. Ectopic expression of YB-1 and
      Puralpha in glial cells synergistically stimulated viral promoter activity via
      the 23-bp sequence element. Results from mutational studies revealed that
      residues between amino acids 75 and 203 of YB-1 and between amino acids 85 and
      215 of Puralpha are important for the interaction between these two proteins.
      Functional studies with glial cells indicated that the region within Puralpha
      which mediates its association with YB-1 and binding to the 23-bp sequence is
      important for the observed activation of the JCV promoter by the Puralpha and YB
      1 proteins. The results of this study suggest that the cooperative interaction
      between YB-1 and Puralpha mediates the synergistic activation of the human
      polyomavirus JCV genome by these cellular proteins. The importance of these
      findings for cellular and viral genes which are regulated by Puralpha and YB-1 is
      discussed.

PMID- 10082538
TI  - Human SWI-SNF component BRG1 represses transcription of the c-fos gene.
AB  - Yeast and mammalian SWI-SNF complexes regulate transcription through active
      modification of chromatin structure. Human SW-13 adenocarcinoma cells lack BRG1
      protein, a component of SWI-SNF that has a DNA-dependent ATPase activity
      essential for SWI-SNF function. Expression of BRG1 in SW-13 cells potentiated
      transcriptional activation by the glucocorticoid receptor, which is known to
      require SWI-SNF function. BRG1 also specifically repressed transcription from a
      transfected c-fos promoter and correspondingly blocked transcriptional activation
      of the endogenous c-fos gene. Mutation of lysine residue 798 in the DNA-dependent
      ATPase domain of BRG1 significantly reduced its ability to repress c-fos
      transcription. Repression by BRG1 required the cyclic AMP response element of the
      c-fos promoter but not nearby binding sites for Sp1, YY1, or TFII-I. Using human
      C33A cervical carcinoma cells, which lack BRG1 and also express a nonfunctional
      Rb protein, transcriptional repression by BRG1 was weak unless wild-type Rb was
      also supplied. Interestingly, Rb-dependent repression by BRG1 was found to take
      place through a pathway that is independent of transcription factor E2F.

PMID- 10082539
TI  - COUP-TF upregulates NGFI-A gene expression through an Sp1 binding site.
AB  - The formation of various tissues requires close communication between two groups
      of cells, epithelial and mesenchymal cells. COUP-TFs are transcription factors
      which have been shown to have functions in embryonic development. COUP-TFI is
      expressed mainly in the nervous system, and its targeted deletion leads to
      defects in the central and peripheral nervous systems. COUP-TFII is highly
      expressed in the mesenchymal component of the developing organs. A null mutation
      of COUP-TFII results in the malformation of the heart and blood vessels. From
      their expression pattern, we proposed that COUP-TFs regulate paracrine signals
      important for mesenchymal cell-epithelial cell interactions. In order to identify
      genes regulated by COUP-TF in this process, a rat urogenital mesenchymal cell
      line was stably transfected with a COUP-TFI expression vector. We found that NGFI
      A, a gene with important functions in brain, organ, and vasculature development,
      has elevated mRNA and protein levels upon overexpression of COUP-TFI in these
      cells. A study of the promoter region of this gene identified a COUP-TF
      responsive element between positions -64 and -46. Surprisingly, this region
      includes binding sites for members of the Sp1 family of transcription factors but
      no COUP-TF binding site. Mutations that abolish the Sp1 binding activity also
      impair the transactivation of the NGFI-A promoter by COUP-TF. Two regions of the
      COUP-TF molecule are shown to be important for NGFI-A activation: the DNA binding
      domain and the extreme C terminus of the putative ligand binding domain. The C
      terminal region is likely to be important for interaction with coactivators. In
      fact, the coactivators p300 and steroid receptor activator 1 can enhance the
      transactivation of the NGFI-A promoter induced by COUP-TFI. Finally, we
      demonstrated that COUP-TF can directly interact with Sp1. Taken together, these
      results suggest that NGFI-A is a target gene for COUP-TFs and that the Sp1 family
      of transcription factors mediates its regulation by COUP-TFs.

PMID- 10082540
TI  - New insights into the mechanism of inhibition of p53 by simian virus 40 large T
      antigen.
AB  - Simian virus 40 (SV40) large tumor antigen (T antigen) has been shown to inhibit
      p53-dependent transcription by preventing p53 from binding to its cognate cis
      element. Data presented in this report provide the first direct functional
      evidence that T antigen, under certain conditions, may also repress p53-dependent
      transcription by a mechanism in which the transactivation domain of p53 is
      abrogated while DNA binding is unaffected. Specifically, p53 purified as a
      complex with T antigen from mouse cells was found to bind DNA as a
      transcriptionally inactive intact complex, while that purified from human cells
      was found to bind DNA independently of T antigen and could activate p53-dependent
      transcription. This difference in activity may be dependent on a different
      interaction of T antigen with mouse and human p53 and, in addition, on the
      presence of super T, which is found only in transformed rodent cells. These
      results suggest that subtle yet important differences exist between the
      inhibition of p53 by T antigen in mouse and human cells. The implications of this
      finding with respect to SV40-associated malignancies are discussed.

PMID- 10082541
TI  - Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl
      xL, regulate the survival of murine pro-B lymphocytes.
AB  - Hematopoietic cells require cytokine-initiated signals for survival as well as
      proliferation. The pathways that transduce these signals, ensuring timely
      regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4)
      transcription factor, Bcl-xL, and constitutively active mutants of components in
      Ras signal transduction pathways have been identified as key regulation proteins
      affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that
      expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf
      mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.
      NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL
      levels are regulated through the membrane proximal portion in the cytoplasmic
      domain of the receptor (betac chain), which is shared by IL-3 and granulocyte
      macrophage colony-stimulating factor. Activation of either pathway alone is
      insufficient to ensure cell survival, indicating that multiple independent signal
      transduction pathways mediate the survival of developing B-lymphoid cells.

PMID- 10082542
TI  - Confluence of vascular endothelial cells induces cell cycle exit by inhibiting
      p42/p44 mitogen-activated protein kinase activity.
AB  - Like other cellular models, endothelial cells in cultures stop growing when they
      reach confluence, even in the presence of growth factors. In this work, we have
      studied the effect of cellular contact on the activation of p42/p44 mitogen
      activated protein kinase (MAPK) by growth factors in mouse vascular endothelial
      cells. p42/p44 MAPK activation by fetal calf serum or fibroblast growth factor
      was restrained in confluent cells in comparison with the activity found in sparse
      cells. Consequently, the induction of c-fos, MAPK phosphatases 1 and 2 (MKP1/2),
      and cyclin D1 was also restrained in confluent cells. In contrast, the activation
      of Ras and MEK-1, two upstream activators of the p42/p44 MAPK cascade, was not
      impaired when cells attained confluence. Sodium orthovanadate, but not okadaic
      acid, restored p42/p44 MAPK activity in confluent cells. Moreover, lysates from
      confluent 1G11 cells more effectively inactivated a dually phosphorylated active
      p42 MAPK than lysates from sparse cells. These results, together with the fact
      that vanadate-sensitive phosphatase activity was higher in confluent cells,
      suggest that phosphatases play a role in the down-regulation of p42/p44 MAPK
      activity. Enforced long-term activation of p42/p44 MAPK by expression of the
      chimera DeltaRaf-1:ER, which activates the p42/p44 MAPK cascade at the level of
      Raf, enhanced the expression of MKP1/2 and cyclin D1 and, more importantly,
      restored the reentry of confluent cells into the cell cycle. Therefore,
      inhibition of p42/p44 MAPK activation by cell-cell contact is a critical step
      initiating cell cycle exit in vascular endothelial cells.

PMID- 10082543
TI  - Regulation of V(D)J recombination by transcriptional promoters.
AB  - Enhancer elements potentiate the rearrangement of antigen receptor loci via
      changes in the accessibility of gene segment clusters to V(D)J recombinase. Here,
      we show that enhancer activity per se is insufficient to target T-cell receptor
      beta miniloci for DbetaJbeta recombination. Instead, a promoter situated 5' to
      Dbeta1 (PDbeta) was required for efficient rearrangement of chromosomal
      substrates. A critical function for promoters in regulating gene segment
      accessibility was further supported by the ability of heterologous promoters to
      direct rearrangement of enhancer-containing substrates. Importantly, activation
      of a synthetic tetracycline-inducible promoter (Ptet) positioned upstream from
      the Dbeta gene segment was sufficient to target recombination of miniloci lacking
      a distal enhancer element. The latter result suggests that DNA loops, generated
      by interactions between flanking promoter and enhancer elements, are not required
      for efficient recognition of chromosomal gene segments by V(D)J recombinase.
      Unexpectedly, the Ptet substrate exhibited normal levels of rearrangement despite
      its retention of a hypermethylated DNA status within the DbetaJbeta cluster.
      Together, our findings support a model in which promoter activation, rather than
      intrinsic properties of enhancers, is the primary determinant for regulating
      recombinational accessibility within antigen receptor loci.

PMID- 10082544
TI  - Conserved loop I of U5 small nuclear RNA is dispensable for both catalytic steps
      of pre-mRNA splicing in HeLa nuclear extracts.
AB  - The function of conserved regions of the metazoan U5 snRNA was investigated by
      reconstituting U5 small nuclear ribonucleoprotein particles (snRNPs) from
      purified snRNP proteins and HeLa or Xenopus U5 snRNA mutants and testing their
      ability to restore splicing to U5-depleted nuclear extracts. Substitution of
      conserved nucleotides comprising internal loop 2 or deletion of internal loop 1
      had no significant effect on the ability of reconstituted U5 snRNPs to complement
      splicing. However, deletion of internal loop 2 abolished U5 activity in splicing
      and spliceosome formation. Surprisingly, substitution of the invariant loop 1
      nucleotides with a GAGA tetraloop had no effect on U5 activity. Furthermore, U5
      snRNPs reconstituted from an RNA formed by annealing the 5' and 3' halves of the
      U5 snRNA, which lacked all loop 1 nucleotides, complemented both steps of
      splicing. Thus, in contrast to yeast, loop 1 of the human U5 snRNA is dispensable
      for both steps of splicing in HeLa nuclear extracts. This suggests that its
      function can be compensated for in vitro by other spliceosomal components: for
      example, by proteins associated with the U5 snRNP. Consistent with this idea,
      immunoprecipitation studies indicated that several functionally important U5
      proteins associate stably with U5 snRNPs containing a GAGA loop 1 substitution.

PMID- 10082545
TI  - A kinase activity associated with simian virus 40 large T antigen phosphorylates
      upstream binding factor (UBF) and promotes formation of a stable initiation
      complex between UBF and SL1.
AB  - Simian virus 40 large T antigen is a multifunctional protein which has been shown
      to modulate the expression of genes transcribed by RNA polymerase I (Pol I), II,
      and III. In all three transcription systems, a key step in the activation process
      is the recruitment of large T antigen to the promoter by direct protein-protein
      interaction with the TATA binding protein (TBP)-TAF complexes, namely, SL1,
      TFIID, and TFIIIB. However, our previous studies on large T antigen stimulation
      of Pol I transcription also revealed that the binding to the TBP-TAFI complex SL1
      is not sufficient to activate transcription. To further define the molecular
      mechanism involved in large T antigen-mediated Pol I activation, we examined
      whether the high-mobility group box-containing upstream binding factor (UBF)
      plays any role in this process. Here, using cell labeling experiments, we showed
      that large T antigen expression induces an increase in UBF phosphorylation.
      Further biochemical analysis demonstrated that UBF is phosphorylated by a kinase
      activity that is strongly associated with large T antigen, and that the carboxy
      terminal activation domain of UBF is required for the phosphorylation to occur.
      Using in vitro reconstituted transcription assays, we demonstrated that the
      inability of alkaline phosphatase treated UBF to efficiently activate
      transcription can be rescued by large T antigen. Moreover, we showed that large T
      antigen-induced UBF phosphorylation promotes the formation of a stable UBF-SL1
      complex. Together, these results provide strong evidence for an important role
      for the large T antigen-associated kinase in mediating the stimulation of RNA Pol
      I transcription.

PMID- 10082546
TI  - Specific binding of high-mobility-group I (HMGI) protein and histone H1 to the
      upstream AT-rich region of the murine beta interferon promoter: HMGI protein acts
      as a potential antirepressor of the promoter.
AB  - The high-mobility-group I (HMGI) protein is a nonhistone component of active
      chromatin. In this work, we demonstrate that HMGI protein specifically binds to
      the AT-rich region of the murine beta interferon (IFN-beta) promoter localized
      upstream of the murine virus-responsive element (VRE). Contrary to what has been
      described for the human promoter, HMGI protein did not specifically bind to the
      VRE of the murine IFN-beta promoter. Stably transfected promoters carrying
      mutations on this HMGI binding site displayed delayed virus-induced kinetics of
      transcription. When integrated into chromatin, the mutated promoter remained
      repressed and never reached normal transcriptional activity. Such a phenomenon
      was not observed with transiently transfected promoters upon which chromatin was
      only partially reconstituted. Using UV footprinting, we show that the upstream AT
      rich sequences of the murine IFN-beta promoter constitute a preferential binding
      region for histone H1. Transfection with a plasmid carrying scaffold attachment
      regions as well as incubation with distamycin led to the derepression of the IFN
      beta promoter stably integrated into chromatin. In vitro, HMGI protein was able
      to displace histone H1 from the upstream AT-rich region of the wild-type promoter
      but not from the promoter carrying mutations on the upstream high-affinity HMGI
      binding site. Our results suggest that the binding of histone H1 to the upstream
      AT-rich region of the promoter might be partly responsible for the constitutive
      repression of the promoter. The displacement by HMGI protein of histone H1 could
      help to convert the IFN-beta promoter from a repressed to an active state.

PMID- 10082547
TI  - An in vitro system recapitulates chromatin remodeling at the PHO5 promoter.
AB  - The Saccharomyces cerevisiae gene PHO5 is an excellent system with which to study
      regulated changes in chromatin structure. The PHO5 promoter is packaged into four
      positioned nucleosomes under repressing conditions; upon induction, the structure
      of these nucleosomes is altered such that the promoter DNA becomes accessible to
      nucleases. We report here the development and characterization of an in vitro
      system in which partially purified PHO5 minichromosomes undergo promoter
      chromatin remodeling. Several hallmarks of the PHO5 chromatin transition in vivo
      were reproduced in this system. Chromatin remodeling of PHO5 minichromosomes
      required the transcription factors Pho4 and Pho2, was localized to the promoter
      region of PHO5, and was independent of the chromatin-remodeling complex Swi-Snf.
      In vitro chromatin remodeling also required the addition of fractionated nuclear
      extract and hydrolyzable ATP. This in vitro system should serve as a useful tool
      for identifying the components required for this reaction and for elucidating the
      mechanism by which the PHO5 promoter chromatin structure is changed.

PMID- 10082548
TI  - Requirement of ATM in phosphorylation of the human p53 protein at serine 15
      following DNA double-strand breaks.
AB  - Microinjection of the restriction endonuclease HaeIII, which causes DNA double
      strand breaks with blunt ends, induces nuclear accumulation of p53 protein in
      normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this
      induction of p53 accumulation is not observed in ataxia telangiectasia (AT)
      fibroblasts. HaeIII-induced p53 protein in normal fibroblasts is phosphorylated
      at serine 15, as determined by immunostaining with an antibody specific for
      phosphorylated serine 15 of p53. This phosphorylation correlates well with p53
      accumulation. Treatment with lactacystin (an inhibitor of the proteasome) or heat
      shock leads to similar levels of p53 accumulation in normal and AT fibroblasts,
      but the p53 protein lacks a phosphorylated serine 15. Following microinjection of
      HaeIII into lactacystin-treated normal fibroblasts, lactacystin-induced p53
      protein is phosphorylated at serine 15 and stabilized even in the presence of
      cycloheximide. However, neither stabilization nor phosphorylation at serine 15 is
      observed in AT fibroblasts under the same conditions. These results indicate the
      significance of serine 15 phosphorylation for p53 stabilization after DNA double
      strand breaks and an absolute requirement for ATM in this phosphorylation
      process.

PMID- 10082549
TI  - MOT1 can activate basal transcription in vitro by regulating the distribution of
      TATA binding protein between promoter and nonpromoter sites.
AB  - MOT1 is an ATPase which can dissociate TATA binding protein (TBP)-DNA complexes
      in a reaction requiring ATP hydrolysis. Consistent with this observation, MOT1
      can repress basal transcription in vitro. Paradoxically, however, some genes,
      such as HIS4, appear to require MOT1 as an activator of transcription in vivo. To
      further investigate the function of MOT1 in basal transcription, we performed in
      vitro transcription reactions using yeast nuclear extracts depleted of MOT1.
      Quantitation of MOT1 revealed that it is an abundant protein, with nuclear
      extracts from wild-type cells containing a molar excess of MOT1 over TBP.
      Surprisingly, MOT1 can weakly activate basal transcription in vitro. This
      activation by MOT1 is detectable with amounts of MOT1 that are approximately
      stoichiometric to TBP. With amounts of MOT1 similar to those present in wild-type
      nuclear extracts, MOT1 behaves as a weak repressor of basal transcription. These
      results suggest that MOT1 might activate transcription via an indirect mechanism
      in which limiting TBP can be liberated from nonpromoter sites for use at
      promoters. In support of this idea, excess nonpromoter DNA sequesters TBP and
      represses transcription, but this effect can be reversed by addition of MOT1.
      These results help to reconcile previous in vitro and in vivo results and expand
      the repertoire of transcriptional control strategies to include factor-assisted
      redistribution of TBP between promoter and nonpromoter sites.

PMID- 10082550
TI  - Phosphorylation of TFIIA stimulates TATA binding protein-TATA interaction and
      contributes to maximal transcription and viability in yeast.
AB  - Posttranslational modification of general transcription factors may be an
      important mechanism for global gene regulation. The general transcription factor
      IIA (TFIIA) binds to the TATA binding protein (TBP) and is essential for high
      level transcription mediated by various activators. Modulation of the TFIIA-TBP
      interaction is a likely target of transcriptional regulation. We report here that
      Toa1, the large subunit of yeast TFIIA, is phosphorylated in vivo and that this
      phosphorylation stabilizes the TFIIA-TBP-DNA complex and is required for high
      level transcription. Alanine substitution of serine residues 220, 225, and 232
      completely eliminated in vivo phosphorylation of Toa1, although no single amino
      acid substitution of these serine residues eliminated phosphorylation in vivo.
      Phosphorylated TFIIA was 30-fold more efficient in forming a stable complex with
      TBP and TATA DNA. Dephosphorylation of yeast-derived TFIIA reduced DNA binding
      activity, and recombinant TFIIA could be stimulated by in vitro phosphorylation
      with casein kinase II. Yeast strains expressing the toa1 S220/225/232A showed
      reduced high-level transcriptional activity at the URA1, URA3, and HIS3 promoters
      but were viable. However, S220/225/232A was synthetically lethal when combined
      with an alanine substitution mutation at W285, which disrupts the TFIIA-TBP
      interface. Phosphorylation of TFIIA could therefore be an important mechanism of
      transcription modulation, since it stimulates TFIIA-TBP association, enhances
      high-level transcription, and contributes to yeast viability.

PMID- 10082551
TI  - Activated notch inhibits myogenic activity of the MADS-Box transcription factor
      myocyte enhancer factor 2C.
AB  - Skeletal muscle gene expression is dependent on combinatorial associations
      between members of the MyoD family of basic helix-loop-helix (bHLH) transcription
      factors and the myocyte enhancer factor 2 (MEF2) family of MADS-box transcription
      factors. The transmembrane receptor Notch interferes with the muscle-inducing
      activity of myogenic bHLH proteins, and it has been suggested that this
      inhibitory activity of Notch is directed at an essential cofactor that recognizes
      the DNA binding domains of the myogenic bHLH proteins. Given that MEF2 proteins
      interact with the DNA binding domains of myogenic bHLH factors to cooperatively
      regulate myogenesis, we investigated whether members of the MEF2 family might
      serve as targets for the inhibitory effects of Notch on myogenesis. We show that
      a constitutively activated form of Notch specifically blocks DNA binding by
      MEF2C, as well as its ability to cooperate with MyoD and myogenin to activate
      myogenesis. Responsiveness to Notch requires a 12-amino-acid region of MEF2C
      immediately adjacent to the DNA binding domain that is unique to this MEF2
      isoform. Two-hybrid assays and coimmunoprecipitations show that this region of
      MEF2C interacts directly with the ankyrin repeat region of Notch. These findings
      reveal a novel mechanism for Notch-mediated inhibition of myogenesis and
      demonstrate that the Notch signaling pathway can discriminate between different
      members of the MEF2 family.

PMID- 10082552
TI  - Tat activates human immunodeficiency virus type 1 transcriptional elongation
      independent of TFIIH kinase.
AB  - Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional
      elongation by recruitment of the human transcription elongation factor P-TEFb,
      consisting of Cdk9 and cyclin T1, to the HIV-1 promoter via cooperative binding
      to the nascent HIV-1 transactivation response RNA element. The Cdk9 kinase
      activity has been shown to be essential for P-TEFb to hyperphosphorylate the
      carboxy-terminal domain (CTD) of RNA polymerase II and mediate Tat
      transactivation. Recent reports have shown that Tat can also interact with the
      multisubunit transcription factor TFIIH complex and increase the phosphorylation
      of CTD by the Cdk-activating kinase (CAK) complex associated with the core TFIIH.
      These observations have led to the proposal that TFIIH and P-TEFb may act
      sequentially and in a concerted manner to promote phosphorylation of CTD and
      increase polymerase processivity. Here, we show that under conditions in which a
      specific and efficient interaction between Tat and P-TEFb is observed, only a
      weak interaction between Tat and TFIIH that is independent of critical amino acid
      residues in the Tat transactivation domain can be detected. Furthermore,
      immunodepletion of CAK under high-salt conditions, which allow CAK to be
      dissociated from core-TFIIH, has no effect on either basal HIV-1 transcription or
      Tat activation of polymerase elongation in vitro. Therefore, unlike the P-TEFb
      kinase activity that is essential for Tat activation of HIV-1 transcriptional
      elongation, the CAK kinase associated with TFIIH appears to be dispensable for
      Tat function.

PMID- 10082553
TI  - Recruitment of TATA-binding protein-TAFI complex SL1 to the human ribosomal DNA
      promoter is mediated by the carboxy-terminal activation domain of upstream
      binding factor (UBF) and is regulated by UBF phosphorylation.
AB  - Human rRNA synthesis by RNA polymerase I requires at least two auxiliary factors,
      upstream binding factor (UBF) and SL1. UBF is a DNA binding protein with multiple
      HMG domains that binds directly to the CORE and UCE elements of the ribosomal DNA
      promoter. The carboxy-terminal region of UBF is necessary for transcription
      activation and has been shown to be extensively phosphorylated. SL1, which
      consists of TATA-binding protein (TBP) and three associated factors (TAFIs), does
      not have any sequence-specific DNA binding activity, and its recruitment to the
      promoter is mediated by specific protein interactions with UBF. Once on the
      promoter, the SL1 complex makes direct contact with the DNA promoter and directs
      promoter-specific initiation of transcription. To investigate the mechanism of
      UBF-dependent transcriptional activation, we first performed protein-protein
      interaction assays between SL1 and a series of UBF deletion mutants. This
      analysis indicated that the carboxy-terminal domain of UBF, which is necessary
      for transcriptional activation, makes direct contact with the TBP-TAFI complex
      SL1. Since this region of UBF can be phosphorylated, we then tested whether this
      modification plays a functional role in the interaction with SL1. Alkaline
      phosphatase treatment of UBF completely abolished the ability of UBF to interact
      with SL1; moreover, incubation of the dephosphorylated UBF with nuclear extracts
      from exponentially growing cells was able to restore the UBF-SL1 interaction. In
      addition, DNase I footprinting analysis and in vitro-reconstituted transcription
      assays with phosphatase-treated UBF provided further evidence that UBF
      phosphorylation plays a critical role in the regulation of the recruitment of SL1
      to the ribosomal DNA promoter and stimulation of UBF-dependent transcription.

PMID- 10082554
TI  - Functional domains of c-myc promoter binding protein 1 involved in
      transcriptional repression and cell growth regulation.
AB  - We initially identified c-myc promoter binding protein 1 (MBP-1), which
      negatively regulates c-myc promoter activity, from a human cervical carcinoma
      cell expression library. Subsequent studies on the biological role of MBP-1
      demonstrated induction of cell death in fibroblasts and loss of anchorage
      independent growth, reduced invasive ability, and tumorigenicity of human breast
      carcinoma cells. To investigate the potential role of MBP-1 as a transcriptional
      regulator, a chimeric protein containing MBP-1 fused to the DNA binding domain of
      the yeast transactivator factor GAL4 was constructed. This fusion protein
      exhibited repressor activity on the herpes simplex virus thymidine kinase
      promoter via upstream GAL4 DNA binding sites. Structure-function analysis of
      mutant MBP-1 in the context of the GAL4 DNA binding domain revealed that MBP-1
      transcriptional repressor domains are located in the N terminus (amino acids 1 to
      47) and C terminus (amino acids 232 to 338), whereas the activation domain lies
      in the middle (amino acids 140 to 244). The N-terminal domain exhibited stronger
      transcriptional repressor activity than the C-terminal region. When the N
      terminal repressor domain was transferred to a potent activator, transcription
      was strongly inhibited. Both of the repressor domains contained hydrophobic
      regions and had an LXVXL motif in common. Site-directed mutagenesis in the
      repressor domains indicated that the leucine residues in the LXVXL motif are
      required for transcriptional repression. Mutation of the leucine residues in the
      common motif of MBP-1 also abrogated the repressor activity on the c-myc
      promoter. In addition, the leucine mutant forms of MBP-1 failed to suppress cell
      growth in fibroblasts like wild-type MBP-1. Taken together, our results indicate
      that MBP-1 is a complex cellular factor containing multiple transcriptional
      regulatory domains that play an important role in cell growth regulation.

PMID- 10082555
TI  - Expression of mutated Paramecium telomerase RNAs in vivo leads to templating
      errors that resemble those made by retroviral reverse transcriptase.
AB  - Telomeric DNA consists of short, tandemly repeated sequences at the ends of
      chromosomes. Telomeric DNA in the ciliate Paramecium tetraurelia is synthesized
      by an error-prone telomerase with an RNA template specific for GGGGTT repeats. We
      have previously shown that misincorporation of TTP residues at the telomerase RNA
      templating nucleotide C52 accounts for the 30% GGGTTT repeats randomly
      distributed in wild-type telomeres. To more completely characterize variable
      repeat synthesis in P. tetraurelia, telomerase RNA genes mutated at C52 (A, U,
      and G) were expressed in vivo. De novo telomeric repeats from transformants
      indicate that the predominant TTP misincorporation error seen in the wild-type
      telomerase is dependent on the presence of a C residue at template position 52.
      Paradoxically, the effects of various other telomerase RNA template and alignment
      region mutations on de novo telomeres include significant changes in fidelity, as
      well as the synthesis of aberrant, 5-nucleotide telomeric repeats. The occurrence
      of deletion errors and the altered fidelity of mutated P. tetraurelia telomerase,
      in conjunction with misincorporation by the wild-type enzyme, suggest that the
      telomerase RNA template domain may be analogous to homopolymeric mutational hot
      spots that lead to similar errors by the human immunodeficiency virus
      proofreading-deficient reverse transcriptase.

PMID- 10082556
TI  - Subtle mutagenesis by ends-in recombination in malaria parasites.
AB  - The recent advent of gene-targeting techniques in malaria (Plasmodium) parasites
      provides the means for introducing subtle mutations into their genome. Here, we
      used the TRAP gene of Plasmodium berghei as a target to test whether an ends-in
      strategy, i.e., targeting plasmids of the insertion type, may be suitable for
      subtle mutagenesis. We analyzed the recombinant loci generated by insertion of
      linear plasmids containing either base-pair substitutions, insertions, or
      deletions in their targeting sequence. We show that plasmid integration occurs
      via a double-strand gap repair mechanism. Although sequence heterologies located
      close (less than 450 bp) to the initial double-strand break (DSB) were often lost
      during plasmid integration, mutations located 600 bp and farther from the DSB
      were frequently maintained in the recombinant loci. The short lengths of gene
      conversion tracts associated with plasmid integration into TRAP suggests that an
      ends-in strategy may be widely applicable to modify plasmodial genes and perform
      structure-function analyses of their important products.

PMID- 10082557
TI  - CD5 negatively regulates the T-cell antigen receptor signal transduction pathway:
      involvement of SH2-containing phosphotyrosine phosphatase SHP-1.
AB  - The negative regulation of T- or B-cell antigen receptor signaling by CD5 was
      proposed based on studies of thymocytes and peritoneal B-1a cells from CD5
      deficient mice. Here, we show that CD5 is constitutively associated with
      phosphotyrosine phosphatase activity in Jurkat T cells. CD5 was found associated
      with the Src homology 2 (SH2) domain containing hematopoietic phosphotyrosine
      phosphatase SHP-1 in both Jurkat cells and normal phytohemagglutinin-expanded T
      lymphoblasts. This interaction was increased upon T-cell receptor (TCR)-CD3 cell
      stimulation. CD5 co-cross-linking with the TCR-CD3 complex down-regulated the TCR
      CD3-increased Ca2+ mobilization in Jurkat cells. In addition, stimulation of
      Jurkat cells or normal phytohemagglutinin-expanded T lymphoblasts through TCR-CD3
      induced rapid tyrosine phosphorylation of several protein substrates, which was
      substantially diminished after CD5 cross-linking. The CD5-regulated substrates
      included CD3zeta, ZAP-70, Syk, and phospholipase Cgammal but not the Src family
      tyrosine kinase p56(lck). By mutation of all four CD5 intracellular tyrosine
      residues to phenylalanine, we found the membrane-proximal tyrosine at position
      378, which is located in an immunoreceptor tyrosine-based inhibitory (ITIM)-like
      motif, crucial for SHP-1 association. The F378 point mutation ablated both SHP-1
      binding and the down-regulating activity of CD5 during TCR-CD3 stimulation. These
      results suggest a critical role of the CD5 ITIM-like motif, which by binding to
      SHP-1 mediates the down-regulatory activity of this receptor.

PMID- 10082558
TI  - Design of conditionally active STATs: insights into STAT activation and gene
      regulatory function.
AB  - The STAT (signal transducer and activator of transcription) signaling pathway is
      activated by a large number of cytokines and growth factors. We sought to design
      a conditionally active STAT that could not only provide insight into basic
      questions about STAT function but also serve as a powerful tool to determine the
      precise biological role of STATs. To this end, we have developed a conditionally
      active STAT by fusing STATs with the ligand-binding domain of the estrogen
      receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are
      estrogen-inducible transcription factors that retain the functional and
      biochemical characteristics of the cognate wild-type STATs. In addition, these
      tools have allowed us to evaluate separately the contribution of tyrosine
      phosphorylation and dimerization to STAT function. We have for the first time
      provided experimental data supporting the model that the only apparent role of
      STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is
      sufficient to unmask a latent STAT nuclear localization sequence and induce
      nuclear translocation, sequence-specific DNA binding, and transcriptional
      activity.

PMID- 10082559
TI  - p70 S6 kinase is regulated by protein kinase Czeta and participates in a
      phosphoinositide 3-kinase-regulated signalling complex.
AB  - p70 S6 kinase (p70S6K) is an important regulator of cell proliferation. Its
      activation by growth factor requires phosphorylation by various inputs on
      multiple sites. Data accumulated thus far support a model whereby p70S6K
      activation requires sequential phosphorylations at proline-directed residues in
      the putative autoinhibitory pseudosubstrate domain, as well as threonine 389.
      Threonine 229, a site in the catalytic loop is phosphorylated by phosphoinositide
      dependent kinase 1 (PDK-1). Experimental evidence suggests that p70S6K activation
      requires a phosphoinositide 3-kinase (PI3-K)-dependent signal(s). However, the
      intermediates between PI3-K and p70S6K remain unclear. Here, we have identified
      PI3-K-regulated atypical protein kinase C (PKC) isoform PKCzeta as an upstream
      regulator of p70S6K. In coexpression experiments, we found that a kinase-inactive
      PKCzeta mutant antagonized activation of p70S6K by epidermal growth factor, PDK
      1, and activated Cdc42 and PI3-K. While overexpression of a constitutively active
      PKCzeta mutant (myristoylated PKCzeta [myr-PKCzeta]) only modestly activated
      p70S6K, this mutant cooperated with PDK-1 activation of p70S6K. PDK-1-induced
      activation of a C-terminal truncation mutant of p70S6K was also enhanced by myr
      PKCzeta. Moreover, we have found that p70S6K can associate with both PDK-1 and
      PKCzeta in vivo in a growth factor-independent manner, while PDK-1 and PKCzeta
      can also associate with each other, suggesting the existence of a multimeric PI3
      K signalling complex. This work provides evidence for a link between a phorbol
      ester-insensitive PKC isoform and p70S6K. The existence of a PI3-K-dependent
      signalling complex may enable efficient activation of p70S6K in cells.

PMID- 10082560
TI  - Overlapping specificities of base excision repair, nucleotide excision repair,
      recombination, and translesion synthesis pathways for DNA base damage in
      Saccharomyces cerevisiae.
AB  - The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to
      be conducted primarily through the base excision repair pathway. The Escherichia
      coli endonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase
      associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of
      damaged pyrimidines (H. J. You, R. L. Swanson, and P. W. Doetsch, Biochemistry
      37:6033-6040, 1998). The biological relevance of the N-glycosylase-associated AP
      lyase activity in the repair of abasic sites is not well understood, and the
      majority of AP sites in vivo are thought to be processed by Apn1p, the major AP
      endonuclease in yeast. We have found that yeast cells simultaneously lacking
      Ntg1p, Ntg2p, and Apn1p are hyperrecombinogenic (hyper-rec) and exhibit a mutator
      phenotype but are not sensitive to the oxidizing agents H2O2 and menadione. The
      additional disruption of the RAD52 gene in the ntg1 ntg2 apn1 triple mutant
      confers a high degree of sensitivity to these agents. The hyper-rec and mutator
      phenotypes of the ntg1 ntg2 apn1 triple mutant are further enhanced by the
      elimination of the nucleotide excision repair pathway. In addition, removal of
      either the lesion bypass (Rev3p-dependent) or recombination (Rad52p-dependent)
      pathway specifically enhances the hyper-rec or mutator phenotype, respectively.
      These data suggest that multiple pathways with overlapping specificities are
      involved in the removal of, or tolerance to, spontaneous DNA damage in S.
      cerevisiae. In addition, the fact that these responses to induced and spontaneous
      damage depend upon the simultaneous loss of Ntg1p, Ntg2p, and Apn1p suggests a
      physiological role for the AP lyase activity of Ntg1p and Ntg2p in vivo.

PMID- 10082561
TI  - C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers
      of newborn mice.
AB  - We previously showed that the rate of hepatocyte proliferation in livers from
      newborn C/EBPalpha knockout mice was increased. An examination of cell cycle
      related proteins showed that the cyclin-dependent kinase (CDK) inhibitor p21
      level was reduced in the knockout animals compared to that in wild-type
      littermates. Here we show additional cell cycle-associated proteins that are
      affected by C/EBPalpha. We have observed that C/EBPalpha controls the composition
      of E2F complexes through interaction with the retinoblastoma (Rb)-like protein,
      p107, during prenatal liver development. S-phase-specific E2F complexes
      containing E2F, DP, cdk2, cyclin A, and p107 are observed in the developing
      liver. In wild-type animals these complexes disappear by day 18 of gestation and
      are no longer present in the newborn animals. In the C/EBPalpha mutant, the S
      phase-specific complexes do not diminish and persist to birth. The elevation of
      levels of the S-phase-specific E2F-p107 complexes in C/EBPalpha knockout mice
      correlates with the increased expression of several E2F-dependent genes such as
      those that encode cyclin A, proliferating cell nuclear antigen, and p107. The
      C/EBPalpha-mediated regulation of E2F binding is specific, since the deletion of
      another C/EBP family member, C/EBPbeta, does not change the pattern of E2F
      binding during prenatal liver development. The addition of bacterially expressed,
      purified His-C/EBPalpha to the E2F binding reaction resulted in the disruption of
      E2F complexes containing p107 in nuclear extracts from C/EBPalpha knockout mouse
      livers. Ectopic expression of C/EBPalpha in cultured cells also leads to a
      reduction of E2F complexes containing Rb family proteins. Coimmunoprecipitation
      analyses revealed an interaction of C/EBPalpha with p107 but none with cdk2,
      E2F1, or cyclin A. A region of C/EBPalpha that has sequence similarity to E2F is
      sufficient for the disruption of the E2F-p107 complexes. Despite its role as a
      DNA binding protein, C/EBPalpha brings about a change in E2F complex composition
      through a protein-protein interaction. The disruption of E2F-p107 complexes
      correlates with C/EBPalpha-mediated growth arrest of hepatocytes in newborn
      animals.

PMID- 10082562
TI  - Transcriptional activation by ETS and leucine zipper-containing basic helix-loop
      helix proteins.
AB  - The immunoglobulin mu heavy-chain gene enhancer contains closely juxtaposed
      binding sites for ETS and leucine zipper-containing basic helix-loop-helix (bHLH
      zip) proteins. To understand the mu enhancer function, we have investigated
      transcription activation by the combination of ETS and bHLH-zip proteins. The
      bHLH-zip protein TFE3, but not USF, cooperated with the ETS domain proteins PU.1
      and Ets-1 to activate a tripartite domain of this enhancer. Deletion mutants were
      used to identify the domains of the proteins involved. Both TFE3 and USF enhanced
      Ets-1 DNA binding in vitro by relieving the influence of an autoinhibitory domain
      in Ets-1 by direct protein-protein associations. Several regions of Ets-1 were
      found to be necessary, whereas the bHLH-zip domain was sufficient for this
      effect. Our studies define novel interactions between ETS and bHLH-zip proteins
      that may regulate combinatorial transcription activation by these protein
      families.

PMID- 10082563
TI  - Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion
      and migration through integrin alphavbeta3, promotes endothelial cell survival,
      and induces angiogenesis in vivo.
AB  - Fisp12 was first identified as a secreted protein encoded by a growth factor
      inducible immediate-early gene in mouse fibroblasts, whereas its human ortholog,
      CTGF (connective tissue growth factor), was identified as a mitogenic activity in
      conditioned media of human umbilical vein endothelial cells. Fisp12/CTGF is a
      member of a family of secreted proteins that includes CYR61, Nov, Elm-1, Cop
      1/WISP-2, and WISP-3. Fisp12/CTGF has been shown to promote cell adhesion and
      mitogenesis in both fibroblasts and endothelial cells and to stimulate cell
      migration in fibroblasts. These findings, together with the localization of
      Fisp12/CTGF in angiogenic tissues, as well as in atherosclerotic plaques, suggest
      a possible role for Fisp12/CTGF in the regulation of vessel growth during
      development, wound healing, and vascular disease. In this study, we show that
      purified Fisp12 (mCTGF) protein promotes the adhesion of microvascular
      endothelial cells through the integrin receptor alphavbeta3. Furthermore, Fisp12
      stimulates the migration of microvascular endothelial cells in culture, also
      through an integrin-alphavbeta3-dependent mechanism. In addition, the presence of
      Fisp12 promotes endothelial cell survival when cells are plated on laminin and
      deprived of growth factors, a condition that otherwise induces apoptosis. In
      vivo, Fisp12 induces neovascularization in rat corneal micropocket implants.
      These results demonstrate that Fisp12 is a novel angiogenic inducer and suggest a
      direct role for Fisp12 in the adhesion, migration, and survival of endothelial
      cells during blood vessel growth. Taken together with the recent finding that the
      related protein CYR61 also induces angiogenesis, we suggest that Fisp12/mCTGF and
      CYR61 comprise prototypes of a new family of angiogenic regulators that function,
      at least in part, through integrin-alphavbeta3-dependent pathways.

PMID- 10082564
TI  - An activator binding module of yeast RNA polymerase II holoenzyme.
AB  - The Mediator complex of Saccharomyces cerevisiae is required for both general and
      regulated transcription of RNA polymerase II (PolII) and is composed of two
      stable subcomplexes (Srb4 and Rgr1 subcomplexes). To decipher the function of
      each Mediator subcomplex and to delineate the functional relationship between the
      subcomplexes, we characterized the compositions and biochemical activities of
      PolII-Mediator complexes (holoenzymes) prepared from several Mediator mutant
      strains of S. cerevisiae. We found that holoenzymes devoid of a functional Gal11
      module were defective for activated but not basal transcription in a
      reconstituted in vitro system. This activation-specific defect was correlated
      with a crippled physical interaction to transcriptional activator proteins, which
      could be bypassed by artificial recruitment of a mutant holoenzyme to a promoter.
      Consistent with this observation, a direct interaction between Gal11 and gene
      specific transcriptional activator proteins was detected by far-Western analyses
      and column binding assays. In contrast, the srb5 deletion mutant holoenzyme was
      defective for both basal and activated transcription, despite its capacity for
      activator binding that is comparable to that of the wild-type holoenzyme. These
      results demonstrate that the Gal11 module of the Rgr1 subcomplex is required for
      the efficient recruitment of PolII holoenzyme to a promoter via activator
      specific interactions, while the Srb4 subcomplex functions in the modulation of
      general polymerase activity.

PMID- 10082565
TI  - Binding of Gal4p and bicoid to nucleosomal sites in yeast in the absence of
      replication.
AB  - The yeast transcriptional activator Gal4p can bind to sites in nucleosomal DNA in
      vivo which it is unable to access in vitro. One event which could allow proteins
      to bind to otherwise inaccessible sites in chromatin in living cells is DNA
      replication. To determine whether replication is required for Gal4p to bind to
      nucleosomal sites in yeast, we have used previously characterized chromatin
      reporters in which Gal4p binding sites are incorporated into nucleosomes. We find
      that Gal4p is able to perturb nucleosome positioning via nucleosomal binding
      sites in yeast arrested either in G1, with alpha-factor, or in G2/M, with
      nocodazole. Similar results were obtained whether Gal4p synthesis was induced
      from the endogenous promoter by growth in galactose medium or by an artificial,
      hormone-inducible system. We also examined binding of the Drosophila
      transcriptional activator Bicoid, which belongs to the homeodomain class of
      transcription factors. We show that Bicoid, like Gal4p, can bind to nucleosomal
      sites in SWI+ and swi1Delta yeast and in the absence of replication. Our results
      indicate that some feature of the intracellular environment other than DNA
      replication or the SWI-SNF complex permits factor access to nucleosomal sites.

PMID- 10082566
TI  - Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA
      damage.
AB  - We report here that the Rad51 recombinase is cleaved in mammalian cells during
      the induction of apoptosis by ionizing radiation (IR) exposure. The results
      demonstrate that IR induces Rad51 cleavage by a caspase-dependent mechanism.
      Further support for involvement of caspases is provided by the finding that IR
      induced proteolysis of Rad51 is inhibited by Ac-DEVD-CHO. In vitro studies show
      that Rad51 is cleaved by caspase 3 at a DVLD/N site. Stable expression of a Rad51
      mutant in which the aspartic acid residues were mutated to alanines (AVLA/N)
      confirmed that the DVLD/N site is responsible for the cleavage of Rad51 in IR
      induced apoptosis. The functional significance of Rad51 proteolysis is supported
      by the finding that, unlike intact Rad51, the N- and C-terminal cleavage products
      fail to exhibit recombinase activity. In cells, overexpression of the Rad51(D-A)
      mutant had no effect on activation of caspase 3 but did abrogate in part the
      apoptotic response to IR exposure. We conclude that proteolytic inactivation of
      Rad51 by a caspase-mediated mechanism contributes to the cell death response
      induced by DNA damage.

PMID- 10082567
TI  - Mutational disruption of plasma membrane trafficking of Saccharomyces cerevisiae
      Yor1p, a homologue of mammalian multidrug resistance protein.
AB  - The ATP binding cassette (ABC) transporter protein Yor1p was identified on the
      basis of its ability to elevate oligomycin resistance when it was overproduced
      from a high-copy-number plasmid. Analysis of the predicted amino acid sequence of
      Yor1p indicated that this protein was a new member of a subfamily of ABC
      transporter proteins defined by the multidrug resistance protein (MRP). In this
      work, Yor1p is demonstrated to localize to the Saccharomyces cerevisiae plasma
      membrane by both indirect immunofluorescence and biochemical fractionation
      studies. Several mutations were generated in the amino-terminal nucleotide
      binding domain (NBD1) of Yor1p to test if the high degree of sequence
      conservation in this region of the protein was important for function. Deletion
      of a phenylalanine residue at Yor1p position 670 led to a mutant protein that
      appeared to be retained in the endoplasmic reticulum (ER) and that was unstable.
      As shown by others, deletion of the analogous residue from a second mammalian MRP
      family member, the cystic fibrosis transmembrane conductance regulator (CFTR),
      also led to retention of this normally plasma membrane-localized protein in the
      ER. Changes in the spacing between or the sequences flanking functional motifs of
      Yor1p NBD1 led to defective trafficking or decreased activity of the mutant
      proteins. Analyses of the degradation of wild-type and DeltaF670 Yor1p indicated
      that the half-life of DeltaF670 Yor1p was dramatically shortened. While the
      vacuole was the primary site for turnover of wild-type Yor1p, degradation of
      DeltaF670 Yor1p was found to be more complex with both proteasomal and vacuolar
      contributions.

PMID- 10082568
TI  - Roles of the "dispensable" portions of RAG-1 and RAG-2 in V(D)J recombination.
AB  - V(D)J recombination is initiated by introduction of site-specific double-stranded
      DNA breaks by the RAG-1 and RAG-2 proteins. The broken DNA ends are then joined
      by the cellular double-strand break repair machinery. Previous work has shown
      that truncated (core) versions of the RAG proteins can catalyze V(D)J
      recombination, although less efficiently than their full-length counterparts. It
      is not known whether truncating RAG-1 and/or RAG-2 affects the cleavage step or
      the joining step of recombination. Here we examine the effects of truncated RAG
      proteins on recombination intermediates and products. We found that while
      truncated RAG proteins generate lower levels of recombination products than their
      full-length counterparts, they consistently generate 10-fold higher levels of one
      class of recombination intermediates, termed signal ends. Our results suggest
      that this increase in signal ends does not result from increased cleavage, since
      levels of the corresponding intermediates, coding ends, are not elevated. Thus,
      removal of the "dispensable" regions of the RAG proteins impairs proper
      processing of recombination intermediates. Furthermore, we found that removal of
      portions of the dispensable regions of RAG-1 and RAG-2 affects the efficiency of
      product formation without altering the levels of recombination intermediates.
      Thus, these evolutionarily conserved sequences play multiple, important roles in
      V(D)J recombination.

PMID- 10082569
TI  - An N-terminal truncation uncouples the sex-transforming and dosage compensation
      functions of sex-lethal.
AB  - In Drosophila melanogaster, Sex-lethal (Sxl) controls autoregulation and sexual
      differentiation by alternative splicing but regulates dosage compensation by
      translational repression. To elucidate how Sxl functions in splicing and
      translational regulation, we have ectopically expressed a full-length Sxl protein
      (Sx.FL) and a protein lacking the N-terminal 40 amino acids (Sx-N). The Sx.FL
      protein recapitulates the activity of Sxl gain-of-function mutations, as it is
      both sex transforming and lethal in males. In contrast, the Sx-N protein unlinks
      the sex-transforming and male-lethal effects of Sxl. The Sx-N proteins are
      compromised in splicing functions required for sexual differentiation, displaying
      only partial autoregulatory activity and almost no sex-transforming activity. On
      the other hand, the Sx-N protein does retain substantial dosage compensation
      function and kills males almost as effectively as the Sx.FL protein. In the
      course of our analysis of the Sx.FL and Sx-N transgenes, we have also uncovered a
      novel, negative autoregulatory activity, in which Sxl proteins bind to the 3'
      untranslated region of Sxl mRNAs and decrease Sxl protein expression. This
      negative autoregulatory activity may be a homeostasis mechanism.

PMID- 10082570
TI  - A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion protein
      AML1-ETO-expressing mice, functions in hematopoietic cell differentiation.
AB  - Using PCR-coupled subtractive screening-representational difference analysis, we
      have cloned a novel gene from AML1-ETO knockin mice. This gene is highly
      expressed in the yolk sac and fetal liver of the knockin mice. Nucleotide
      sequence analysis indicates that its cDNA contains an 1,107-bp open reading frame
      encoding a 368-amino-acid polypeptide. Further protein sequence and protein
      translation analysis shows that it belongs to a family of ubiquitin-specific
      proteases (UBP), and its molecular mass is 43 kDa. Therefore, we have named this
      gene UBP43. Like other ubiquitin proteases, the UBP43 protein has
      deubiquitinating enzyme activity. Protein ubiquitination has been implicated in
      many important cellular events. In wild-type adult mice, UBP43 is highly
      expressed in the thymus and in peritoneal macrophages. Among nine different
      murine hematopoietic cell lines analyzed, UBP43 expression is detectable only in
      cell lines related to the monocytic lineage. Furthermore, its expression is
      regulated during cytokine-induced monocytic cell differentiation. We have
      investigated its function in the hematopoietic myeloid cell line M1. UBP43 was
      introduced into M1 cells by retroviral gene transfer, and several high-expressing
      UBP43 clones were obtained for further study. Morphologic and cell surface marker
      examination of UBP43/M1 cells reveals that overexpression of UBP43 blocks
      cytokine-induced terminal differentiation of monocytic cells. These data suggest
      that UBP43 plays an important role in hematopoiesis by modulating either the
      ubiquitin-dependent proteolytic pathway or the ubiquitination state of another
      regulatory factor(s) during myeloid cell differentiation.

PMID- 10082571
TI  - The SKN-1 amino-terminal arm is a DNA specificity segment.
AB  - The Caenorhabditis elegans SKN-1 protein binds DNA through a basic region like
      those of bZIP proteins and through a flexible amino-terminal arm segment similar
      to those with which numerous helix-turn-helix proteins bind to bases in the minor
      groove. A recent X-ray crystallographic structure suggests that the SKN-1 amino
      terminal arm provides only nonspecific DNA binding. In this study, however, we
      demonstrate that this segment mediates recognition of an AT-rich element that is
      part of the preferred SKN-1 binding site and thereby significantly increases the
      sequence specificity with which SKN-1 binds DNA. Mutagenesis experiments show
      that multiple amino acid residues within the arm are involved in binding. These
      residues provide binding affinity through distinct but partially redundant
      interactions and enhance specificity by discriminating against alternate sites.
      The AT-rich element minor groove is important for binding of the arm, which
      appears to affect DNA conformation in this region. This conformational effect
      does not seem to involve DNA bending, however, because the arm does not appear to
      affect a modest DNA bend that is induced by SKN-1. The data illustrate an example
      of how a small, flexible protein segment can make an important contribution to
      DNA binding specificity through multiple interactions and mechanisms.

PMID- 10082572
TI  - HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.
AB  - Aberrant activation of the HOX, MEIS, and PBX homeodomain protein families is
      associated with leukemias, and retrovirally driven coexpression of HOXA9 and
      MEIS1 is sufficient to induce myeloid leukemia in mice. Previous studies have
      demonstrated that HOX-9 and HOX-10 paralog proteins are unique among HOX
      homeodomain proteins in their capacity to form in vitro cooperative DNA binding
      complexes with either the PBX or MEIS protein. Furthermore, PBX and MEIS proteins
      have been shown to form in vivo heterodimeric DNA binding complexes with each
      other. We now show that in vitro DNA site selection for MEIS1 in the presence of
      HOXA9 and PBX yields a consensus PBX-HOXA9 site. MEIS1 enhances in vitro HOXA9
      PBX protein complex formation in the absence of DNA and forms a trimeric
      electrophoretic mobility shift assay (EMSA) complex with these proteins on an
      oligonucleotide containing a PBX-HOXA9 site. Myeloid cell nuclear extracts
      produce EMSA complexes which appear to contain HOXA9, PBX2, and MEIS1, while
      immunoprecipitation of HOXA9 from these extracts results in coprecipitation of
      PBX2 and MEIS1. In myeloid cells, HOXA9, MEIS1, and PBX2 are all strongly
      expressed in the nucleus, where a portion of their signals are colocalized within
      nuclear speckles. However, cotransfection of HOXA9 and PBX2 with or without MEIS1
      minimally influences transcription of a reporter gene containing multiple PBX
      HOXA9 binding sites. Taken together, these data suggest that in myeloid leukemia
      cells MEIS1 forms trimeric complexes with PBX and HOXA9, which in turn can bind
      to consensus PBX-HOXA9 DNA targets.

PMID- 10082573
TI  - Hypersensitive site 2 specifies a unique function within the human beta-globin
      locus control region to stimulate globin gene transcription.
AB  - The human beta-globin locus control region (LCR) harbors both strong chromatin
      opening and enhancer activity when assayed in transgenic mice. To understand the
      contribution of individual DNase I hypersensitive sites (HS) to the function of
      the human beta-globin LCR, we have mutated the core elements within the context
      of a yeast artificial chromosome (YAC) carrying the entire locus and then
      analyzed the effect of these mutations on the formation of LCR HS elements and
      expression of the genes in transgenic mice. In the present study, we examined the
      consequences of two different HS2 mutations. We first generated seven YAC
      transgenic lines bearing a deletion of the 375-bp core enhancer of HS2. Single
      copy HS2 deletion mutants exhibited severely depressed HS site formation and
      expression of all of the human beta-globin genes at every developmental stage,
      confirming that HS2 is a vital, integral component of the LCR. We also analyzed
      four transgenic lines in which the core element of HS2 was replaced by that of
      HS3 and found that while HS3 is able to restore the chromatin-opening activity of
      the LCR, it is not able to functionally replace HS2 in mediating high-level
      globin gene transcription. These results continue to support the hypothesis that
      HS2, HS3, and HS4 act as a single, integral unit to regulate human globin gene
      transcription as a holocomplex, but they can also be interpreted to say that
      formation of a DNase I hypersensitive holocomplex alone is not sufficient for
      mediating high-level globin gene transcription. We therefore propose that the
      core elements must productively interact with one another to generate a unique
      subdomain within the nucleoprotein holocomplex that interacts in a stage-specific
      manner with individual globin gene promoters.

PMID- 10082574
TI  - Allosteric regulation of the discriminative responsiveness of retinoic acid
      receptor to natural and synthetic ligands by retinoid X receptor and DNA.
AB  - Transcriptional activation by retinoids is mediated through two families of
      nuclear receptors, all-trans-retinoic acid (RARs) and 9-cis retinoic acid
      receptors (RXRs). Conformationally restricted retinoids are used to achieve
      selective activation of RAR isotype alpha, beta or gamma, which reduces side
      effects in therapeutical applications. Synthetic retinoids mimic some of all
      trans retinoic acid biological effects in vivo but interact differently with the
      ligand binding domain of RARalpha and induce distinct structural transitions of
      the receptor. In this report, we demonstrate that RAR-selective ligands have
      distinct quantitative activation properties which are reflected by their
      abilities to promote interaction of DNA-bound human RXRalpha (hRXRalpha)
      hRARalpha heterodimers with the nuclear receptor coactivator (NCoA) SRC-1 in
      vitro. The hormone response element core motifs spacing defined the relative
      affinity of liganded heterodimers for two NCoAs, SRC-1 and RIP140. hRXRalpha
      activating function 2 was critical to confer hRARalpha full responsiveness but
      not differential sensitivity of hRARalpha to natural or synthetic retinoids. We
      also provide evidence showing that lysines located in helices 3 and 4, which
      define part of hRARalpha NCoA binding surface, contribute differently to (i) the
      transcriptional activity and (ii) the interaction of RXR-RAR heterodimers with
      SRC-1, when challenged by either natural or RAR-selective retinoids. Thus, ligand
      structure, DNA, and RXR exert allosteric regulations on hRARalpha conformation
      organized as a DNA-bound heterodimer. We suggest that the use of physically
      distinct NCoA binding interfaces may be important in controlling specific genes
      by conformationally restricted ligands.

PMID- 10082575
TI  - Modulation of cell proliferation by cytokeratins K10 and K16.
AB  - The members of the large keratin family of cytoskeletal proteins are expressed in
      a carefully regulated tissue- and differentiation-specific manner. Although these
      proteins are thought to be involved in imparting mechanical integrity to
      epithelial cells, the functional significance of their complex differential
      expression is still unclear. Here we provide new data suggesting that the
      expression of particular keratins may influence cell proliferation. Specifically,
      we demonstrate that the ectopic expression of K10 inhibits the proliferation of
      human keratinocytes in culture, while K16 expression appears to promote the
      proliferation of these cells. Other keratins, such as K13 or K14, do not
      significantly alter this parameter. K10-induced inhibition is reversed by the
      coexpression of K16 but not that of K14. These results are coherent with the
      observed expression pattern of these proteins in the epidermis: basal,
      proliferative keratinocytes express K14; when they terminally differentiate,
      keratinocytes switch off K14 and start K10 expression, whereas in response to
      hyperproliferative stimuli, K16 replaces K10. The characteristics of this process
      indicate that K10 and K16 act on the retinoblastoma (Rb) pathway, as (i) K10
      induced inhibition is hampered by cotransfection with viral oncoproteins which
      interfere with pRb but not with p53; (ii) K10-mediated cell growth arrest is
      rescued by the coexpression of specific cyclins, cyclin-dependent kinases (CDKs),
      or cyclin-CDK complexes; (iii) K10-induced inhibition does not take place in Rb
      deficient cells but is restored in these cells by cotransfection with pRb or p107
      but not p130; (iv) K16 efficiently rescues the cell growth arrest induced by pRb
      in HaCaT cells but not that induced by p107 or p130; and (v) pRb phosphorylation
      and cyclin D1 expression are reduced in K10-transfected cells and increased in
      K16-transfected cells. Finally, using K10 deletion mutants, we map this
      inhibitory function to the nonhelical terminal domains of K10, hypervariable
      regions in which keratin-specific functions are thought to reside, and
      demonstrate that the presence of one of these domains is sufficient to promote
      cell growth arrest.

PMID- 10082576
TI  - Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell
      cycle dysfunction.
AB  - Both p53 and ATM are checkpoint regulators with roles in genetic stabilization
      and cancer susceptibility. ATM appears to function in the same DNA damage
      checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosis and
      tumor suppression in response to cell cycle dysregulation is unknown. In this
      study, we tested the role of murine ataxia telangiectasia protein (Atm) in a
      transgenic mouse brain tumor model in which p53-mediated apoptosis results in
      tumor suppression. These p53-mediated activities are induced by tissue-specific
      inactivation of pRb family proteins by a truncated simian virus 40 large T
      antigen in brain epithelium. We show that p53-dependent apoptosis,
      transactivation, and tumor suppression are unaffected by Atm deficiency,
      suggesting that signaling in the DNA damage pathway is distinct from that in the
      oncogene-induced pathway. In addition, we show that Atm deficiency has no overall
      effect on tumor growth and progression in this model.

PMID- 10082577
TI  - Control of replicative life span in human cells: barriers to clonal expansion
      intermediate between M1 senescence and M2 crisis.
AB  - The accumulation of genetic abnormalities in a developing tumor is driven, at
      least in part, by the need to overcome inherent restraints on the replicative
      life span of human cells, two of which-senescence (M1) and crisis (M2)-have been
      well characterized. Here we describe additional barriers to clonal expansion
      (Mint) intermediate between M1 and M2, revealed by abrogation of tumor-suppressor
      gene (TSG) pathways by individual human papillomavirus type 16 (HPV16) proteins.
      In human fibroblasts, abrogation of p53 function by HPVE6 allowed escape from M1,
      followed up to 20 population doublings (PD) later by a second viable
      proliferation arrest state, MintE6, closely resembling M1. This occurred despite
      abrogation of p21(WAF1) induction but was associated with and potentially
      mediated by a further approximately 3-fold increase in p16(INK4a) expression
      compared to its level at M1. Expression of HPVE7, which targets pRb (and
      p21(WAF1)), also permitted clonal expansion, but this was limited predominantly
      by increasing cell death, resulting in a MintE7 phenotype similar to M2 but
      occurring after fewer PD. This was associated with, and at least partly due to,
      an increase in nuclear p53 content and activity, not seen in younger cells
      expressing E7. In a different cell type, thyroid epithelium, E7 also allowed
      clonal expansion terminating in a similar state to MintE7 in fibroblasts. In
      contrast, however, there was no evidence for a p53-regulated pathway; E6 was
      without effect, and the increases in p21(WAF1) expression at M1 and MintE7 were
      p53 independent. These data provide a model for clonal evolution by successive
      TSG inactivation and suggest that cell type diversity in life span regulation may
      determine the pattern of gene mutation in the corresponding tumors.

PMID- 10082578
TI  - Maturation of the myogenic program is induced by postmitotic expression of
      insulin-like growth factor I.
AB  - The molecular mechanisms underlying myogenic induction by insulin-like growth
      factor I (IGF-I) are distinct from its proliferative effects on myoblasts. To
      determine the postmitotic role of IGF-I on muscle cell differentiation, we
      derived L6E9 muscle cell lines carrying a stably transfected rat IGF-I gene under
      the control of a myosin light chain (MLC) promoter-enhancer cassette. Expression
      of MLC-IGF-I exclusively in differentiated L6E9 myotubes, which express the
      embryonic form of myosin heavy chain (MyHC) and no endogenous IGF-I, resulted in
      pronounced myotube hypertrophy, accompanied by activation of the neonatal MyHC
      isoform. The hypertrophic myotubes dramatically increased expression of myogenin,
      muscle creatine kinase, beta-enolase, and IGF binding protein 5 and activated the
      myocyte enhancer factor 2C gene which is normally silent in this cell line. MLC
      IGF-I induction in differentiated L6E9 cells also increased the expression of a
      transiently transfected LacZ reporter driven by the myogenin promoter,
      demonstrating activation of the differentiation program at the transcriptional
      level. Nuclear reorganization, accumulation of skeletal actin protein, and an
      increased expression of beta1D integrin were also observed. Inhibition of the
      phosphatidyl inositol (PI) 3-kinase intermediate in IGF-I-mediated signal
      transduction confirmed that the PI 3-kinase pathway is required only at early
      stages for IGF-I-mediated hypertrophy and neonatal MyHC induction in these cells.
      Expression of IGF-I in postmitotic muscle may therefore play an important role in
      the maturation of the myogenic program.

PMID- 10082579
TI  - Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in
      regulation of cell motility.
AB  - The coordinated interplay of substrate adhesion and deadhesion is necessary for
      cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF
      I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time
      dependent manner, suggesting that IGF-I triggers the activation of different
      integrins. On the other hand, IGF-I promotes the association of insulin receptor
      substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine
      phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of
      SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF
      I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I
      stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected
      cells. This impairment of cell migration is recovered by reintroduction of a
      catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number
      of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity
      participates in the integrin deactivation process. Although SHP-2 regulates
      mitogen-activated protein kinase activity, the mitogen-activated protein kinase
      kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The
      role of SHP-2 as a general regulator of cell chemotaxis induced by other
      chemotactic agents and integrins is discussed.

PMID- 10082580
TI  - Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine
      motif together with an acidic amino acid cluster.
AB  - Furin is a subtilisin-related endoprotease which processes a wide range of
      bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where
      proteolytic activation of many precursor proteins takes place. A significant
      fraction of furin, however, cycles among the TGN, the plasma membrane, and
      endosomes, indicating that the accumulation in the TGN reflects a dynamic
      localization process. The cytosolic domain of furin is necessary and sufficient
      for TGN localization, and two signals are responsible for retrieval of furin to
      the TGN. A tyrosine-based (YKGL) motif mediates internalization of furin from the
      cell surface into endosomes. An acidic cluster that is part of two casein kinase
      II phosphorylation sites (SDSEEDE) is then responsible for retrieval of furin
      from endosomes to the TGN. In addition, the acidic EEDE sequence also mediates
      endocytic activity. Here, we analyzed the sorting of furin in polarized
      epithelial cells. We show that furin is delivered to the basolateral surface of
      MDCK cells, from where a significant fraction of the protein can return to the
      TGN. A phenylalanine-isoleucine motif together with the acidic EEDE cluster is
      required for basolateral sorting and constitutes a novel signal regulating
      intracellular traffic of furin.

PMID- 10082581
TI  - SAG, a novel zinc RING finger protein that protects cells from apoptosis induced
      by redox agents.
AB  - SAG (sensitive to apoptosis gene) was cloned as an inducible gene by 1,10
      phenanthroline (OP), a redox-sensitive compound and an apoptosis inducer. SAG
      encodes a novel zinc RING finger protein that consists of 113 amino acids with a
      calculated molecular mass of 12.6 kDa. SAG is highly conserved during evolution,
      with identities of 70% between human and Caenorhabditis elegans sequences and 55%
      between human and yeast sequences. In human tissues, SAG is ubiquitously
      expressed at high levels in skeletal muscles, heart, and testis. SAG is localized
      in both the cytoplasm and the nucleus of cells, and its gene was mapped to
      chromosome 3q22-24. Bacterially expressed and purified human SAG binds to zinc
      and copper metal ions and prevents lipid peroxidation induced by copper or a free
      radical generator. When overexpressed in several human cell lines, SAG protects
      cells from apoptosis induced by redox agents (the metal chelator OP and zinc or
      copper metal ions). Mechanistically, SAG appears to inhibit and/or delay metal
      ion-induced cytochrome c release and caspase activation. Thus, SAG is a cellular
      protective molecule that appears to act as an antioxidant to inhibit apoptosis
      induced by metal ions and reactive oxygen species.

PMID- 10082582
TI  - Xist yeast artificial chromosome transgenes function as X-inactivation centers
      only in multicopy arrays and not as single copies.
AB  - X-chromosome inactivation in female mammals is controlled by the X-inactivation
      center (Xic). This locus is required for inactivation in cis and is thought to be
      involved in the counting process which ensures that only a single X chromosome
      remains active per diploid cell. The Xist gene maps to the Xic region and has
      been shown to be essential for inactivation in cis. Transgenesis represents a
      stringent test for defining the minimal region that can carry out the functions
      attributed to the Xic. Although YAC and cosmid Xist-containing transgenes have
      previously been reported to be capable of cis inactivation and counting, the
      transgenes were all present as multicopy arrays and it was unclear to what extent
      individual copies are functional. Using two different yeast artificial
      chromosomes (YACs), we have found that single-copy transgenes, unlike multicopy
      arrays, can induce neither inactivation in cis nor counting. These results
      demonstrate that despite their large size and the presence of Xist, the YACs that
      we have tested lack sequences critical for autonomous function with respect to X
      inactivation.

PMID- 10082583
TI  - cdk1- and cdk2-mediated phosphorylation of MyoD Ser200 in growing C2 myoblasts:
      role in modulating MyoD half-life and myogenic activity.
AB  - We have examined the role of protein phosphorylation in the modulation of the key
      muscle-specific transcription factor MyoD. We show that MyoD is highly
      phosphorylated in growing myoblasts and undergoes substantial dephosphorylation
      during differentiation. MyoD can be efficiently phosphorylated in vitro by either
      purified cdk1-cyclin B or cdk1 and cdk2 immunoprecipitated from proliferative
      myoblasts. Comparative two-dimensional tryptic phosphopeptide mapping combined
      with site-directed mutagenesis revealed that cdk1 and cdk2 phosphorylate MyoD on
      serine 200 in proliferative myoblasts. In addition, when the seven proline
      directed sites in MyoD were individually mutated, only substitution of serine 200
      to a nonphosphorylatable alanine (MyoD-Ala200) abolished the slower-migrating
      hyperphosphorylated form of MyoD, seen either in vitro after phosphorylation by
      cdk1-cyclin B or in vivo following overexpression in 10T1/2 cells. The MyoD
      Ala200 mutant displayed activity threefold higher than that of wild-type MyoD in
      transactivation of an E-box-dependent reporter gene and promoted markedly
      enhanced myogenic conversion and fusion of 10T1/2 fibroblasts into muscle cells.
      In addition, the half-life of MyoD-Ala200 protein was longer than that of wild
      type MyoD, substantiating a role of Ser200 phosphorylation in regulating MyoD
      turnover in proliferative myoblasts. Taken together, our data show that direct
      phosphorylation of MyoD Ser200 by cdk1 and cdk2 plays an integral role in
      compromising MyoD activity during myoblast proliferation.

PMID- 10082584
TI  - Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for
      mlh1 mutations.
AB  - Loss of DNA mismatch repair due to mutation or diminished expression of the MLH1
      gene is associated with genome instability and cancer. In this study, we used a
      yeast model system to examine three circumstances relevant to modulation of MLH1
      function. First, overexpression of wild-type MLH1 was found to cause a strong
      elevation of mutation rates at three different loci, similar to the mutator
      effect of MLH1 gene inactivation. Second, haploid yeast strains with any of six
      mlh1 missense mutations that mimic germ line mutations found in human cancer
      patients displayed a strong mutator phenotype consistent with loss of mismatch
      repair function. Five of these mutations affect amino acids that are homologous
      to residues suggested by recent crystal structure and biochemical analysis of
      Escherichia coli MutL to participate in ATP binding and hydrolysis. Finally,
      using a highly sensitive reporter gene, we detected a mutator phenotype of
      diploid yeast strains that are heterozygous for mlh1 mutations. Evidence
      suggesting that this mutator effect results not from reduced mismatch repair in
      the MLH1/mlh1 cells but rather from loss of the wild-type MLH1 allele in a
      fraction of cells is presented. Exposure to bleomycin or to UV irradiation
      strongly enhanced mutagenesis in the heterozygous strain but had little effect on
      the mutation rate in the wild-type strain. This damage-induced hypermutability
      may be relevant to cancer in humans with germ line mutations in only one MLH1
      allele.

PMID- 10082585
TI  - A genetic screen for ribosomal DNA silencing defects identifies multiple DNA
      replication and chromatin-modulating factors.
AB  - Transcriptional silencing in Saccharomyces cerevisiae occurs at several genetic
      loci, including the ribosomal DNA (rDNA). Silencing at telomeres (telomere
      position effect [TPE]) and the cryptic mating-type loci (HML and HMR) depends on
      the silent information regulator genes, SIR1, SIR2, SIR3, and SIR4. However,
      silencing of polymerase II-transcribed reporter genes integrated within the rDNA
      locus (rDNA silencing) requires only SIR2. The mechanism of rDNA silencing is
      therefore distinct from TPE and HM silencing. Few genes other than SIR2 have so
      far been linked to the rDNA silencing process. To identify additional non-Sir
      factors that affect rDNA silencing, we performed a genetic screen designed to
      isolate mutations which alter the expression of reporter genes integrated within
      the rDNA. We isolated two classes of mutants: those with a loss of rDNA silencing
      (lrs) phenotype and those with an increased rDNA silencing (irs) phenotype. Using
      transposon mutagenesis, lrs mutants were found in 11 different genes, and irs
      mutants were found in 22 different genes. Surprisingly, we did not isolate any
      genes involved in rRNA transcription. Instead, multiple genes associated with DNA
      replication and modulation of chromatin structure were isolated. We describe
      these two gene classes, and two previously uncharacterized genes, LRS4 and IRS4.
      Further characterization of the lrs and irs mutants revealed that many had
      alterations in rDNA chromatin structure. Several lrs mutants, including those in
      the cdc17 and rfc1 genes, caused lengthened telomeres, consistent with the
      hypothesis that telomere length modulates rDNA silencing. Mutations in the HDB
      (RPD3) histone deacetylase complex paradoxically increased rDNA silencing by a
      SIR2-dependent, SIR3-independent mechanism. Mutations in rpd3 also restored
      mating competence selectively to sir3Delta MATalpha strains, suggesting
      restoration of silencing at HMR in a sir3 mutant background.

PMID- 10082586
TI  - 5-azacytidine induces transgene silencing by DNA methylation in Chinese hamster
      cells.
AB  - The cytosine analog 5-azacytidine (5-AzaC) is a demethylating agent that is also
      known to induce mutagenesis in mammalian cells. In this study, the mutagenic
      potential of this drug was tested in the G10 and G12 transgenic Chinese hamster
      cell lines, which have a single bacterial gpt gene integrated into the genome at
      different sites, with its expression driven by a simian virus 40 (SV40) promoter.
      We show that the mutation frequencies following a 48-h exposure to different
      concentrations of 5-AzaC were 10 to 20 times higher than those of any of the
      other numerous mutagens that have been tested in the G10-G12 system. Moreover,
      the mutation frequencies were much higher in the G10 cell line than in the G12
      cells. Detailed molecular analysis of the 6-thioguanine (6-TG)-resistant variants
      demonstrated that transgene silencing by de novo DNA methylation and increased
      chromatin condensation in the SV40 promoter was the major factor responsible for
      this high level of 6-TG resistance. As would be expected, exposure to 5-AzaC
      lowered the overall genomic DNA methylation levels, but it unexpectedly caused
      hypermethylation and increased chromatin condensation of the transgene in both
      the G10 and G12 cell lines. These results provide the first evidence that 5-AzaC
      may also induce transgene-specific DNA methylation, a phenomenon that can further
      be used for the elucidation of the mechanism that controls silencing of foreign
      DNA.

PMID- 10082589
TI  - Editorial 
AB  - Remarkable advances have occurred in wound healing during the past decade in both
      basic wound biology, as well as applied research into novel treatments of chronic
      wounds. Newly developed therapies have included the use of growth factors to
      enhance wound epithelialization, and the use of bioengineered dressings,
      including skin substitutes. These advances were recently highlighted in the
      December 1998 JCMS supplement on Wound Care. The lead article in this current
      issue of JCMS focuses on potential mechanisms to establish quantifiable end
      points during wound healing, and speculates on the potential relevance to the
      development of novel therapies. Palenske and Morhenn have found that measurement
      of skin capacitance is a useful tool in determining endpoints in wound healing.
      While our ultimate goal in wound healing is to completely re-epithelialize and
      heal a wound, sometimes interventions are less successful. In evaluating wound
      healing agents in preclinical or early clinical studies, surrogate markers may be
      necessary. Skin capacitance may serve as such a marker. In our Point Counterpoint
      Section, Drs Goldhar and Gratton address the controversial issue of whether
      dermatologists should promote treatment products. There are strong opinions on
      both sides of this question, and these two practitioners have concisely addressed
      the respective sides of this issue. The Grand Rounds Section features an article
      by Bergman and co-authors in which they describe a case of crusted scabies in
      association with HTLV-1. Dermatologists are frequently faced with individuals
      with generalized pruritic eruptions, where scabies is frequently in the
      differential diagnosis. Indeed, scabies is quite common worldwide. However,
      crusted scabies, or Norwegian scabies, is much less common, and one clearly has
      to consider immune deficiencies. This report highlights the association of
      crusted scabies with immune deficiency. In our CME sections of this issue, we
      have two important articles. The first, by Dr. Sherri Bale, is a continuation of
      our Genetic Studies in skin disease research, and the article reviews the area of
      mapping of hereditary skin disease by focusing on the gene for pseudoxanthoma
      elasticum. In our day-to- day clinical practice, we frequently discuss the
      clinical diseases we see in terms of prognosis that is often based on our own
      individual experience. Evidence based prognostic modelling may provide a very
      important technique to more accurately assess our patients' outcomes. Drs. Kantor
      and Margolis review the models and enhance our understanding of these techniques.
      In this issue of the Journal we introduce a new section of structured book
      reviews. Two books, Morphologic Diagnosis of Skin Disease and Handbook of
      Dermatology for Primary Care are reviewed. The structured review provides a
      concise analysis of these books to allow readers to determine application of
      these publications to their needs. I hope that each and every one of our readers
      had a very happy holiday season and I wish you the best for the new year.

PMID- 10082588
TI  - Interferon regulatory factor 2 represses the Epstein-Barr virus BamHI Q latency
      promoter in type III latency.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is the essential protein for
      maintenance of the EBV episome and establishment of latency. The BamHI Q promoter
      (Qp) is used for the transcription of EBNA-1 mRNA in type I and type II latency,
      which are EBV infection states exemplified by Burkitt's lymphoma and
      nasopharyngeal carcinoma. However, Qp is inactive in type III latency, and other
      promoters (the BamHI C promoter and/or the BamHI W promoter) are used for EBNA-1.
      The involvement of interferon regulatory factors (IRFs) in the regulation of Qp
      is suggested by the presence of an essential interferon-stimulated response
      element (ISRE) in the promoter. In this work, expression of IRF-2 is shown to be
      inversely associated with Qp status, i.e., IRF-2 levels are high in type III
      latency (when Qp is inactive) and low in type I latency (when Qp is active).
      Also, IRF-2 is identified by electrophoretic mobility shift assay as the major
      protein binding to the Qp ISRE in type III latency. In transient transfection
      assays, IRF-2 represses the activity of Qp-reporter constructs. Overexpression of
      IRF-2 in a type I latency cell line did not activate the endogenous Qp but
      marginally reduced the EBNA-1 mRNA level. Switching from type III latency (Qp
      inactive) to type II latency (Qp active), as produced by cell fusion, is directly
      associated with greatly reduced expression of IRF-2. These data strongly suggest
      that IRF-2 is a negative regulator of Qp and may contribute to the silencing of
      Qp in type III latency.

PMID- 10082590
TI  - Geographic pathology of skin cancer.
AB  - BACKGROUND: The development of knowledge concerning the role of sun exposure in
      causing skin cancer has been a gradual one. OBJECTIVE: This article reviews the
      article by Urbach who used manikin coated with an ultraviolet dosimeter to see
      exactly where on the head and neck the exposure was greatest. CONCLUSION: Urbach
      showed that the areas of greatest sun exposure on his manikins corresponded with
      the location of 95% of squamous cell carcinoma and 66% of basal cell carcinoma.
      He also clearly showed the importance of scattered sky and reflected radiation.

PMID- 10082591
TI  - History of the Atlantic Dermatological Conference: the first 75 years.
AB  - On May 1, 1998, the 75th meeting of the Atlantic Dermatological Conference was
      held in New York City. The following presents the origin, development, and
      sustaining aspects of this treasured annual educational conference. The
      enthusiasm and participation of a record number of attendees is a testimony for
      the continued need for this type of postgraduate education with live patient
      presentation.

PMID- 10082587
TI  - Regulation of early events in integrin signaling by protein tyrosine phosphatase
      SHP-2.
AB  - The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in
      growth factor and cytokine signaling pathways. Previous studies revealed that a
      fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2
      binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with
      adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887
      6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked
      whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl
      phosphorylation increased upon plating of murine fibroblasts onto specific
      extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1
      tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases
      (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced
      mitogen-activated protein kinase (MAPK) activation, and potentiation required
      functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we
      analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being
      plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl
      phosphorylation of several focal adhesion proteins, MAPK activation, and the
      ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but
      were restored upon SHP-2 expression. Our data suggest a positive-feedback model
      in which, upon integrin engagement, basal levels of c-Src activity catalyze the
      tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma
      membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces
      positive signals for downstream events such as MAPK activation and cell shape
      changes.

PMID- 10082592
TI  - Changes in the skin's capacitance after damage to the stratum corneum in humans.
AB  - BACKGROUND: Wound healing is a complex process to study, especially in humans,
      because the endpoint(s) of wound-induction and healing are subjective and,
      therefore, difficult to quantitate. Experiments were performed to establish
      quantifiable endpoints during the wound-induction process in 15 humans (11 women,
      4 men). OBJECTIVE: Measurement of the skin's capacitance was used as a marker for
      the three stages of wound healing: 1) establishment of a wound, 2) the healing
      process, and 3) complete re-epithelialization. METHODS: Superficial wounds in the
      epidermis were generated by tape stripping the skin on the arm of 15 healthy
      volunteers. The skin's capacitance was measured before tape stripping, at various
      time points during the induction of the wound, immediately after glistening of
      the epidermis was achieved, and when the wound had healed according to clinical
      assessment. RESULTS: The values of the skin's capacitance at the point of removal
      of the stratum corneum varied from one individual to the next. Furthermore, the
      number of adhesive cellophane-tape strips needed to remove the stratum corneum
      and achieve glistening, due to accumulation of moisture, differed greatly from
      one volunteer to the next. These experiments suggest that the number of tape
      strips needed to remove the stratum corneum varies with age, sex, and possibly
      ethnicity of the subject. By contrast, during the wound healing process when a
      scab could be visualized, the skin's capacitance measured -122 picofarads (pF).
      Moreover, when the scab had disappeared, the skin's capacitance returned to
      baseline values (0 pF). CONCLUSION: Measurement of the skin's capacitance is a
      useful tool to determine two endpoints in the wounding and healing processes. The
      presence of a scab and the re-establishment of an intact stratum corneum can be
      quantitated easily. Less amenable to quantitation is the exact pF value that
      correlates to a specific type of wound.

PMID- 10082593
TI  - Kaposi's sarcoma in women: A clinicopathologic study.
AB  - BACKGROUND: Although all epidemiologic subsets of Kaposi's sarcoma (KS) (i.e.,
      sporadic, endemic, epidemic, and iatrogenic) have an association with human
      herpes virus 8 (HHV8), these subsets occur in patient populations with
      distinctive clinical features. To a variable degree men outnumber women in all
      subsets. OBJECTIVE: A retrospective study of women with histologically proven
      cutaneous KS was undertaken to determine the clinical and histopathologic
      features, as well as any associations. METHODS: Two hundred and fifty cases of
      cutaneous KS in women from 1975 to 1993 were reviewed. RESULTS: Of the patients,
      80% were more than 60 years of age, and of the patients less than 60 years old,
      28 were from areas of the world with endemic KS. All HIV+ patients but one were
      from areas of endemic KS. Two patients were renal transplant patients. Sixty-four
      percent of the patients had single lesions and 21% recurrent lesions. Twelve
      patients had, or were known to develop, internal involvement, and in six patients
      the cause of death was KS. All but four cases histologically showed areas of
      solid proliferations of tumour cells consistent with plaque or tumour stage. An
      angiosarcoma-like histologic pattern appeared to be associated with more
      aggressive epidemiologic subsets. High mitotic rates were rarely seen and did not
      correlate with aggressive epidemiologic subsets. CONCLUSION: Kaposi's sarcoma in
      women is diagnosed almost exclusively in plaque or tumour stage. The majority of
      women within our study fit within the epidemiologic subset of sporadic KS.

PMID- 10082594
TI  - In vitro C3 mRNA expression in Pemphigus vulgaris: complement activation is
      increased by IL-1alpha and TNF-alpha.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening disease,
      characterized immunohistologically by IgG deposits and complement activation on
      the surface of keratinocytes. Complement activation has been implicated in the
      pathogenesis with C3 deposits in about 90% of patients. OBJECTIVE: In order to
      further elucidate the role of complement in PV and to define which cytokines play
      a role in C3 mRNA expression, we performed an in vitro study in human
      keratinocytes. METHODS: Normal human epidermal keratinocytes (NHuK) were
      incubated with PV serum and C3 mRNA was measured. We previously had shown that IL
      1alpha and TNF-alpha are expressed in PV in vivo and in vitro. Since cytokines
      are able to modulate complement activation, mRNA expression was evaluated in a
      similar experiment after pretreatment using antibodies against IL-1alpha and TNF
      alpha. RESULTS: Incubation of NHuK with PV sera caused their detachment from the
      plates after 20-30 minutes with a complete acantholysis within 12 hours. An early
      C3 mRNA expression was seen after 30 minutes with a peak level after 1 hour.
      Blocking studies, using antibodies against human IL-1alpha and TNF-alpha in NHuK
      together with PV-IgG, showed reduction of in vitro induced acantholysis and
      inhibition of C3 mRNA expression. CONCLUSION: This study supports the hypothesis
      that complement C3 is important in PV acantholysis and that complement activation
      is increased by IL-1alpha and TNF-alpha.

PMID- 10082595
TI  - Recent advances in gene mapping of skin diseases. Pseudoxanthoma elasticum: A
      satisfying sibling study.
AB  - BACKGROUND: A review of the recent progress made in mapping of the hereditary
      skin disease pseudoxanthoma elasticum is presented. METHODS: Affected sib pair
      methods, parametric linkage analysis, and linkage heterogeneity tests are
      reviewed as applied to the effort to identify the location of the pseudoxanthoma
      elasticum gene. RESULTS: Families segregating either autosomal dominant or
      autosomal recessive pseudoxanthoma elasticum mapped to chromosome 16p13.1.
      CONCLUSION: There is a gene for pseudoxanthoma elasticum on chromosome 16p. The
      underlying molecular defect remains to be elucidated.

PMID- 10082596
TI  - Prognostic models: evidence-based approach to predicting disease outcome.
AB  - BACKGROUND: A thorough understanding of the techniques underlying prognostic
      modelling, the potential shortcomings of prognostic models, and their
      applicability to dermatology are important for both clinicians and researchers.
      OBJECTIVE: This article distinguishes between prognostic and explanatory (causal)
      models, discusses some of the techniques used in developing a prognostic model,
      and addresses the importance of model generalizability. CONCLUSION: Prognostic
      models may be useful to the clinician, but must be used with care. It is
      important to critically appraise prognostic models and to assure that they are
      relevant to the population of interest. The ability to critically appraise
      prognostic models is predicated on a thorough understanding of the techniques
      used in their development and evaluation.

PMID- 10082597
TI  - Pseudoporphyria induced by propionic acid derivatives.
AB  - BACKGROUND: Pseudoporphyria is a photosensitive bullous skin disease that is
      distinguished from porphyria cutanea tarda (PCT) by its normal porphyrin profile.
      Drugs are a major cause of this disease, and the list of culprits is continually
      expanding. Nonsteroidal antiinflammatory agents (NSAIDs), especially naproxen and
      other propionic acid derivatives, appear to be the most common offenders.
      OBJECTIVE: The study was carried out to increase awareness about the etiology and
      characteristic features of pseudoporphyria. METHODS: We report two cases of
      pseudoporphyria caused by naproxen and oxaprozin. We review the current English
      language literature on this entity and discuss its clinical features, histology,
      ultrastructure, etiology, and pathophysiology. RESULTS: A 44-year-old man taking
      naproxen for chronic low back pain and a 20-year-old woman on oxaprozin for
      rheumatoid arthritis presented with tense bullae and cutaneous fragility on the
      face and the back of the hands. In both, skin biopsy showed a cell-poor
      subepidermal vesicle with festooning of the dermal papillae. Direct
      immunofluorescence revealed staining at the dermal-epidermal junction and around
      blood vessels with IgG in the first case and with IgG, IgA, and fibrin in the
      second case. Urine collections and serum samples yielded normal levels of uro-
      and coproporphyrins. CONCLUSIONS: Most cases of pseudoporphyria are drug-induced.
      Naproxen, the most common offender, has been associated with a dimorphic clinical
      pattern: a PCT-like presentation and one simulating erythropoietic protoporphyria
      in the pediatric population. Other NSAIDs of the propionic acid family can also
      cause pseudoporphyria.

PMID- 10082598
TI  - Treatment of multiple glomangioma with tuneable dye laser.
AB  - BACKGROUND: Multiple glomangiomas are a rare clinical occurrence. In the past,
      various treatments have been proposed for eradication of these tumours.
      OBJECTIVE: An alternative and effective therapy for multiple glomangioma is
      proposed. RESULTS: The effective clinical response of multiple, painful, bluish
      black lesions on the soles of the feet and the hands, diagnosed as multiple
      glomangioma, to flashlamp tuneable dye laser is reported. CONCLUSION: The
      flashlamp tuneable dye laser is an effective modality in the treatment of
      multiple glomangioma.

PMID- 10082599
TI  - Mohs' surgery as an approach to treatment of multiple skin cancer in rhinophyma.
AB  - BACKGROUND: Skin cancer arising within a rhinophyma is rare, less than would be
      expected from the coexisting chronic active inflammatory process. In rhinophyma,
      multiple coexisting tumours of different histologic types present an unusual
      challenge and have never been described in the literature. OBJECTIVE: The
      treatment approach to multiple tumours occurring in rhinophyma, utilizing Mohs'
      surgery, is reported and discussed. PATIENT: The case of a 64-year-old farmer
      with basal cell carcinoma, squamous cell carcinoma, and basosquamous carcinoma
      occurring in the setting of longstanding rhinophyma is described. CONCLUSION:
      Skin cancer, especially basal and squamous cell carcinoma, diagnosed
      simultaneously in a rhinophyma creates a challenge; the enlarged, inflamed, and
      hypertrophied tissue masks their margins. In our opinion, Mohs' micrographic
      surgery is the treatment of choice and should be primarily considered in view of
      the malignant potential of these tumours, as is shown by the substantial tumour
      extension in the case described.

PMID- 10082600
TI  - Wound healing and chronic wounds.
AB  - A renaissance is taking place in the field of wound healing. Interest in wounds
      has probably never been so great, and a number of key therapeutic advances in the
      last 2 or 3 years are only an indication of more progress to come. In large part,
      we are benefitting from decades of basic research that has provided the knowledge
      and technical advances for many of today's therapeutic products. In this
      manuscript, we will provide the initial framework for wound healing and have
      summarized some key concepts.

PMID- 10082601
TI  - Management of venous ulcers.
AB  - Venous ulcers are the most important cause of leg ulcers in the Western world.
      Traditionally, it was thought that venous ulcers accounted for approximately 80
      to 90% of cases of leg ulceration.1 However, the association of venous and
      arterial disease has increased, probably related to improvement in diagnostic
      techniques, as well as aging of the population. Current data from a cross
      sectional survey in a Swedish population reported that 54% of ulcers were purely
      venous in etiology, giving a prevalence of 0.16%. In an Australian population of
      238,000 screened for chronic ulcers, venous abnormalities were found in 57%, with
      a prevalence of 0.06% in the population. The prevalence of chronic venous ulcers
      increased progressively with age, but there was no significant difference between
      men and women at any age.

PMID- 10082602
TI  - Management of diabetic foot ulcers.

PMID- 10082603
TI  - Tissue engineering.
AB  - Wound care has become one of the first fields to see the benefit of a new
      technology: tissue engineering. Tissue engineering involves the development of
      new materials or devices capable of specific interactions with biological
      tissues. In wound care, these materials may be based entirely on naturally
      occurring tissues and cells, or may be materials that combine synthetics, usually
      polymers, with biological layers. Both wound dressings and skin substitutes are
      available. The complexity of the materials depends on the end uses. Generally,
      synthetics made from polymeric materials such as Tegaderm and Opsite are used as
      wound dressings over relatively simple and shallow wounds or as coverings over
      more complex dressings. Their function is one of protection from water loss,
      drying, and mechanical injury. More complex dressings vary from dermal
      replacements made of reconstituted collagen and chondroitan sulfate backed by a
      polymer layer such as Integra(R) to the complex Apligraftrade mark that contains
      collagen and seeded cells. This last is designed as a complete skin replacement
      or skin substitute. Ultimately, engineered skin will contain all of the
      components necessary to modulate healing and provide the desired response: a
      wound closed with limited scar tissue that retains all of the characteristics of
      natural skin.

PMID- 10082604
TI  - Apligraf living skin equivalent for healing venous and chronic wounds.

PMID- 10082605
TI  - Dermagraft in the treatment of diabetic foot ulcers.

PMID- 10082606
TI  - Extreme intraspecific mitochondrial DNA sequence divergence in Galaxias maculatus
      (Osteichthys: Galaxiidae), one of the world's most widespread freshwater fish.
AB  - Biogeographic controversies surrounding the widespread freshwater fish, Galaxias
      maculatus, were addressed with DNA sequence data. Mitochondrial cytochrome b and
      16S rRNA sequences were obtained from representatives of six populations of this
      species. Substantial levels of cytochrome b (maximum 14.6%) and 16S rRNA sequence
      divergence (maximum 6.0%) were detected between western Pacific (Tasmania-New
      Zealand) and South American (Chile-Falkland Islands) haplotypes. A considerable
      level of divergence was also detected between Tasmanian and New Zealand
      haplotypes (maximum 5.1%) and within and among Chilean and Falkland Island G.
      maculatus (maximum 3. 8%). The phylogenetic structure of haplotypes conflicts
      with the accepted pattern of continental fragmentation. Molecular clock
      calibrations suggest that haplotype divergences postdate the fragmentation of
      Gondwana. These findings point to marine dispersal rather than ancient vicariance
      as an explanation for the wide distribution. The phylogenetic structure of South
      American haplotypes was not consistent with their geographic distribution. We
      consider factors such as population divergence, population size, dispersal,
      secondary contact, and philopatry as potential causes of the high level of mtDNA
      nucleotide diversity in this species.

PMID- 10082607
TI  - Phylogenetic studies of marsupials based on phosphoglycerate kinase DNA
      sequences.
AB  - Phosphoglycerate kinase sequences were obtained for 313 aligned bases of 41
      individuals from 39 marsupial species. In contrast to previous molecular
      analyses, the relationships suggested by these data show a high level of
      congruence with morphologically defined orders and families. Four main
      monophyletic lineages are recognizable. These are the monogeneric orders
      Microbiotheria (Dromiciops australis) and Notoryctemorphia (Notoryctes typhlops),
      a grouping of the American orders Didelphimorphia and Paucituberculata, and the
      Australasian species other than N. typhlops. Within the Australasian lineage,
      there are again four main monophyletic groups; the Dasyuridae, two peramelemorph
      (bandicoot) lineages (one comprised of pseudogene sequences) and the
      Diprotodontia. This topology is not greatly affected by the exclusion of
      pseudogenes except that a clade of syndactylous species (Peramelemorphia plus
      Diprotodontia) is recovered. Two other peramelemorph pseudogenes have inserts of
      about 1 kb with high levels of similarity to LINE 1 elements. The Diprotodontia
      is notable for its relative lack of intersequence variation in comparison to the
      Dasyuromorphia.

PMID- 10082608
TI  - Evolution of ruminant Sarcocystis (Sporozoa) parasites based on small subunit
      rDNA sequences.
AB  - We present an evolutionary analysis of 13 species of Sarcocystis, including 4
      newly sequenced species with ruminants as their intermediate host, based on
      complete small subunit rDNA sequences. Those species with ruminants as their
      intermediate host form a well-supported clade, and there are at least two major
      clades within this group, one containing those species forming microcysts and
      with dogs as their definitive host and the other containing those species forming
      macrocysts and with cats as their definitive host. Those species with
      nonruminants as their intermediate host form the paraphyletic sister group to
      these clades. Most of the species have considerable genotypic differences
      (differing in more than 100 nucleotide positions), except for S. buffalonis and
      S. hirsuta. There is a large suite of genotypic differences indicating that those
      species infecting ruminant and nonruminant hosts have had very different
      evolutionary histories, and similarly for the felid- and canid-infecting species.
      Furthermore, the rDNA sequences that represent the different structural regions
      of the rRNA molecule have very different genotypic behavior within Sarcocystis.
      The evolution of these regions should be functionally constrained, and their
      differences can be explained in terms of the importance of the nucleotide
      sequences to their functions.

PMID- 10082609
TI  - A molecular phylogeny of the pheasants and partridges suggests that these
      lineages are not monophyletic.
AB  - Cytochrome b and D-loop nucleotide sequences were used to study patterns of
      molecular evolution and phylogenetic relationships between the pheasants and the
      partridges, which are thought to form two closely related monophyletic galliform
      lineages. Our analyses used 34 complete cytochrome b and 22 partial D-loop
      sequences from the hypervariable domain I of the D-loop, representing 20 pheasant
      species (15 genera) and 12 partridge species (5 genera). We performed parsimony,
      maximum likelihood, and distance analyses to resolve these phylogenetic
      relationships. In this data set, transversion analyses gave results similar to
      those of global analyses. All of our molecular phylogenetic analyses indicated
      that the pheasants and partridges arose through a rapid radiation, making it
      difficult to establish higher level relationships. However, we were able to
      establish six major lineages containing pheasant and partridge taxa, including
      one lineage containing both pheasants and partridges (Gallus, Bambusicola and
      Francolinus). This result, supported by maximum likelihood tests, indicated that
      the pheasants and partridges do not form independent monophyletic lineages.

PMID- 10082610
TI  - Total evidence, consensus, and bat phylogeny: A distance-based approach.
AB  - Resolution of the total evidence (i.e., character congruence) versus consensus
      (i.e., taxonomic congruence) debate has been impeded by (1) a failure to employ
      validation methods consistently across both tree-building and consensus analyses,
      (2) the incomparability of methods for constructing as opposed to those for
      combining trees, and (3) indifference to aspects of trees other than their
      topologies. We demonstrate a uniform, distance-based approach which allows for
      comparability among the results of character- and taxonomic-congruence studies,
      whether or not an identical suite of taxa has been included in all contributing
      data sets. Our results indicate that total-evidence and consensus trees differ
      little in topology if branch lengths are taken into account when combining two or
      more trees. In addition, when character-state data are converted to distances,
      our method permits their combination with information produced by techniques
      which generate distances directly. Moreover, treating all data sets or trees as
      distance matrices avoids the problem that different numbers of characters in
      contributing studies may confound the conclusions of a total-evidence or
      consensus analysis. Our protocol is illustrated with an example involving bats,
      in which the three component studies based on serology, DNA hybridization, and
      anatomy imply distinct phylogenies. However, the total-evidence and consensus
      trees support a fourth, somewhat different, topology resolved at all but one node
      and which conforms closely to the currently accepted higher category
      classification of Chiroptera.

PMID- 10082611
TI  - Molecular phylogeny and evolutionary history of the tit-tyrants (Aves:
      Tyrannidae).
AB  - Tit-tyrants of the genus Anairetes presently consist of six species; five inhabit
      various regions along the Andean cordillera of South America and one is endemic
      to the Juan Fernandez Islands off the coast of Chile. Data from mtDNA ND2 and Cyt
      b sequences were used to construct a phylogeny for all Anairetes species as well
      as Uromyias agilis, a closely related genus, and Stigmatura as an outgroup, to
      determine their relationships and history of radiation in South America. Results
      strongly supported the following paired relationships: A. nigrocristatus-A.
      reguloides, A. flavirostris-A. alpinus, and A. parulus-A. fernandezianus. This
      dataset, however, could not resolve basal nodes; therefore relationships among
      these pairs remains obscure. Moreover the genus Uromyias, controversially
      separated on morphological criteria from Anairetes, fell within the Anairetes
      clade, although its exact position could not be ascertained with confidence. The
      molecular data indicate that this group probably radiated within the past 2
      million years, concomitant with highly accentuated cycles of global climatic
      change. Certain high altitude areas within the Andes may have been stable during
      global climatic changes and may have served as refugia during the Plio
      Pleistocene.

PMID- 10082612
TI  - Phylogenetic affinities of tarsier in the context of primate Alu repeats.
AB  - Related genomes tend to be colonized by the same or similar repetitive sequence
      elements. Analysis of these elements provides useful taxonomic information. We
      have sequenced Alu repeats from tarsier and compared them with those from
      strepsirhine prosimians (lemurs, sifaka, and galago) and the human genome.
      Tarsier elements cluster with Alu subfamilies from the human lineage. The oldest
      subfamily in tarsier and the most abundant human subfamilies share an RNA
      secondary structure motif which is absent both in the earliest dimeric Alu Jo and
      in the strepsirhine elements. These findings are consistent with the view that
      tarsiers form a sister clade with anthropoides rather than with other prosimians.
      Alu repeats in tarsier genome are relatively old, which indicates a dramatic
      slowdown or even an arrest of these elements' amplification about 20 Myr ago.

PMID- 10082613
TI  - Molecular evolutionary relationships in the avian genus Anthus (Pipits:
      Motacillidae).
AB  - Nucleotide sequences for 1035 bp of the mitochondrial cytochrome b gene were used
      to determine the molecular evolutionary relationships of species in the
      cosmopolitan avian genus Anthus. Phylogenetic analysis of these mtDNA sequences
      supported four major clades within the genus: (1) the small-bodied African
      pipits, (2) a largely Palearctic clade, (3) a largely South American clade, and
      (4) an African-Eurasian-Australian clade. Anthus hellmayri, A. correndera, and A.
      rubescens are shown to be paraphyletic. The possibility of paraphyly within A.
      similis is instead inferred to be the discovery of a new species and supported by
      reference to the museum voucher specimen. Sequence divergence suggests a
      Pliocene/Miocene origin for the genus. Although Anthus cytochrome b is found not
      to be behaving in a clocklike fashion across all taxa, speciation during the
      Pleistocene epoch can be reasonably inferred for the 66% of sister pairs that are
      diverging in a clocklike manner. Base compositions at each codon position are
      similar to those found across a growing number of avian lineages. The resulting
      phylogenetic hypothesis is compared to previous hypotheses of Anthus
      relationships, all of which deal with relationships of a particular species or a
      particular species complex; roughly half of these previous hypotheses are
      supported.

PMID- 10082614
TI  - Phylogenetics of Pinus (Pinaceae) based on nuclear ribosomal DNA internal
      transcribed spacer region sequences.
AB  - A 650-bp portion of the nuclear ribosomal DNA internal transcribed spacer region
      was sequenced in 47 species of Pinus, representing all recognized subsections of
      the genus, and 2 species of Picea and Cathaya as outgroups. Parsimony analyses of
      these length variable sequences were conducted using a manual alignment, 13
      different automated alignments, elision of the automated alignments, and
      exclusion of all alignment ambiguous sites. High and moderately supported clades
      were consistently resolved across the different analyses, while poorly supported
      clades were inconsistently recovered. Comparison of the topologies highlights
      taxa of particularly problematic placement including Pinus nelsonii and P.
      aristata. Within subgenus Pinus, there is moderate support for the monophyly of a
      narrowly circumscribed subsect. Pinus (=subsect. Sylvestres) and strong support
      for a clade of North and Central American hard pines. The Himalayan P. roxburghii
      may be sister species to these "New World hard pines," which have two well
      supported subgroups, subsect. Ponderosae and a clade of the remaining five
      subsections. The position of subsect. Contortae conflicts with its placement in a
      chloroplast DNA restriction site study. Within subgenus Strobus there is
      consistent support for the monophyly of a broadly circumscribed subsect. Strobi
      (including P. krempfii and a polyphyletic subsect. Cembrae) derived from a
      paraphyletic grade of the remaining soft pines. Relationships among subsects.
      Gerardianae, Cembroides, and Balfourianae are poorly resolved. Support for the
      monophyly of subgenus Pinus and subgenus Strobus is not consistently obtained.

PMID- 10082615
TI  - Phylogenetic relationships of North American damselflies of the genus Ischnura
      (Odonata: Zygoptera: Coenagrionidae) based on sequences of three mitochondrial
      genes.
AB  - Relationships of North American damselflies of the genus Ischnura (Odonata:
      Zygoptera: Coenagrionidae) were investigated using a total of 1205 bp from
      portions of three mitochondrial genes: cytochrome b, cytochrome oxidase II, and
      12S ribosomal DNA. Parsimony and neighbor joining analyses reveal a monophyletic
      group consisting of I. damula, I. demorsa, I. perparva, I. posita posita, I.
      posita atezca, I. verticalis, and probably I. denticollis, likely reflecting a
      recent radiation in North America. Ischnura kellicotti, I. barberi, I. prognata,
      I. hastata, I. ramburii, and I. capreola appear to represent much earlier
      divergences in the group. Many previous hypotheses of relationships among North
      American species of Ischnura are not supported by the molecular-based analyses.
      However, there is agreement in many respects between the results of the molecular
      phylogenetic analyses and the morphologically based conclusions of Kennedy (1919,
      "The Phylogeny of the Zygoptera," Ph.D. Dissertation, Cornell University,
      Ithaca). Although results of single-gene phylogenetic analyses often differ,
      there are very few cases in which there is strong support for conflicting
      relationships using different partitions of the data. Combined analysis of all
      three genes yields trees with stronger support overall than the single-gene
      analyses, and the combined data trees that result from diverse data treatments
      are congruent with one another in most respects.

PMID- 10082616
TI  - Papilio phylogeny based on mitochondrial cytochrome oxidase I and II genes.
AB  - Butterflies of the genus Papilio have served as the basis for numerous studies in
      insect physiology, genetics, and ecology. However, phylogenetic work on
      relationships among major lineages in the genus has been limited and
      inconclusive. We have sequenced 2.3 kb of DNA from the mitochondrial cytochrome
      oxidase I and II genes (COI and COII) for 23 Papilio taxa and two outgroups,
      Pachliopta neptunus and Eurytides marcellus, in order to assess the potential of
      these genes for use in Papilio phylogenetics and to examine patterns of gene
      evolution across a broad taxonomic range. Nucleotide and amino acid variation is
      distributed heterogeneously, both within and between genes. Structural features
      of the proteins are not always reliable predictors of variation. In a combined
      analysis, these sequences support a nearly fully resolved topology within
      subgenera and species groups, though higher level relationships among species
      groups require additional study. The most noteworthy findings are that neither
      Papilio alexanor nor P. xuthus belongs in the machaon group and that the subgenus
      Pterourus is paraphyletic with respect to the subgenus Pyrrhosticta. We leave
      relationships among members of the phorcas species group as a trichotomy. These
      two protein coding genes, particularly COI, show excellent performance in
      resolving relationships at the level of species and species groups among
      Papilionidae. We strongly endorse a similar approach for future studies aimed at
      these levels.

PMID- 10082617
TI  - A molecular phylogeny of the patellid limpets (Gastropoda: Patellidae) and its
      implications for the origins of their antitropical distribution.
AB  - The geographical distribution of the limpet family Patellidae is essentially
      antitropical, with 18 species in southern Africa, 10 in the northeastern
      Atlantic, and only 11 species elsewhere (although 4 of these do occur in the
      tropics). One possible explanation for this distribution is the suggestion of a
      recent, perhaps Early Pliocene, migration from southern Africa northward. We
      tested this hypothesis by constructing a molecular phylogeny, derived from
      partial sequences of the 12S and 16S mitochondrial genes, obtained from 34 of the
      38 patellid species. Five species of Nacellidae and 3 of Lottiidae were included
      as potential outgroups. Analysis revealed that two patellid clades are
      represented in the northeastern Atlantic. The typical European patellids (Patella
      sensu stricto) form a single clade within which there is little molecular
      divergence, but are distant from all other patellids, thus refuting the idea of
      recent southern ancestry. From the limited fossil record and estimated rates of
      molecular divergence, we suggest that Patella s.s. may have originated at least
      as early as the Upper Cretaceous and that its northern distribution may have been
      achieved at the same time. The second patellid clade present in the northeastern
      Atlantic is the genus Cymbula, of which the single species Cymbula safiana
      extends from West Africa to the Mediterranean. In contrast to Patella s.s., C.
      safiana is indeed a member of an otherwise southern African clade and may have
      attained its present distribution more recently, during the Miocene. The
      geographical origin of the family remains unclear, but a Mesozoic radiation in
      southern Gondwana is possible. By optimizing morphological characters on our
      molecular tree, we consider the evolution of shell mineralogy and sperm
      ultrastructure. We also discuss the phylogenetic classification of the patellids
      and present some evidence that the family may not be monophyletic.

PMID- 10082618
TI  - Ecological parallelism and cryptic species in the genus Ophiothrix derived from
      mitochondrial DNA sequences.
AB  - We addressed the long-standing problem of species assignment of two nominal
      species of the genus Ophiothrix (Echinodermata, Ophiuroidea) by phylogenetic
      analysis of a segment of the mitochondrial 16S rDNA. Our phylogeny identified two
      distinct mitochondrial lineages that do not correspond to the present species
      assignments. Individuals of the endemic Mediterranean species O. quinquemaculata
      were clustered with individuals of O. fragilis in both mitochondrial lineages. We
      thus suggest that these taxa are not biological species but ecotypes. Differences
      between the two ecotypes in morphological and physiological characteristics may
      be explained by adaptation to environmental conditions at different water depths.
      Despite the observed ecomorphological variability within each of the two major
      mitochondrial lineages, the large genetic distance (9.0-12.0%) between them does
      suggest the existence of two distinct biological species. Their reproductive
      isolation could result from differences in reproductive strategy rather than by
      ecological and/or morphological differentiation.

PMID- 10082619
TI  - PCR primers and amplification methods for 12S ribosomal DNA, the control region,
      cytochrome oxidase I, and cytochrome b in bufonids and other frogs, and an
      overview of PCR primers which have amplified DNA in amphibians successfully.
AB  - New primers (N = 24) for the amplification and sequencing of the complete or near
      complete 12S ribosomal DNA, about 1000 bp of the control region, 390 bp of
      cytochrome oxidase I, and the near complete cytochrome b are described. The 12S
      ribosomal DNA primers successfully amplify DNA in tetrapods; other primers
      successfully amplify DNA in bufonoids and other anurans. An overview of published
      literature and sequence data banks identified 170 mitochondrial and 96 nuclear
      DNA primers that have been used or are highly likely to be useful in amphibians.
      Primer sequences, their locations within genes, and sequence location and
      identity in Xenopus and human and/or mouse are presented for each primer. The
      utility of each primer was estimated by identifying the smallest, yet most
      inclusive, taxonomic category within which each primer has been successful.
      Primers from all published sources are mapped together. We hope that these new
      primers, as well as the list of primers that have been useful in amphibians, will
      encourage further systematic and population genetic studies of amphibians.

PMID- 10082620
TI  - Molecular evolution of the opioid/orphanin gene family.
AB  - Gene duplication is a recurring theme in the evolution of vertebrate polypeptide
      hormones and neuropeptides. These duplication events can lead to the formation of
      gene families in which divergence of function is the usual outcome. In the case
      of the opioid/orphanin family of genes, duplication events have proceeded along
      two paths: (a) an apparent duplication of function as seen in the analgesic
      activity of Proenkephalin and Prodynorphin end-products; and (b) divergence of
      function as seen in the nociceptic activity of Proorphanin end-products or the
      melanocortin (color change and chronic stress regulation) activity of
      Proopiomelanocortin end-products. Although genes coding for Proopiomelanocortin,
      Proenkephalin, Prodynorphin, and Proorphanin have been extensively studied in
      mammals, the distribution and radiation of these genes in nonmammalian
      vertebrates is less well understood. This review will present the hypothesis that
      the radiation of the opioid/orphanin gene family is the result of the duplication
      and divergence of the Proenkephalin gene during the radiation of the chordates.
      To evaluate the Proenkephalin gene duplication hypothesis, a 3'RACE procedure was
      used to screen for the presence of Prodynorphin-related, Proenkephalin-related,
      and Proorphanin-related cDNAs expressed in the brains of nonmammalian
      vertebrates.

PMID- 10082621
TI  - Expression of chicken steroidogenic factor-1 during gonadal sex differentiation.
AB  - The orphan nuclear receptor, steroidogenic factor-1 (SF-1), regulates
      steroidogenic enzyme expression and is essential for gonadal and adrenal
      development in mammals. We have examined expression of the chicken homologue, cSF
      1, during gonadal sex differentiation using whole mount in situ hybridisation and
      RNase protection assays (RPA). In the youngest embryos examined (day 3.5; stages
      21-22), cSF-1 transcripts were already detectable by in situ hybridisation in the
      undifferentiated genital ridge of both sexes. Expression continued in the gonads
      of both sexes at the time of sexual differentiation (days 5.5-6.5; stages 28-30).
      Expression then became higher in developing ovaries compared to testes at days
      6.5-8. 5 (stages 30-35). At day 13.5 (stage 40), when the gonads are well
      differentiated, both ovaries and testes showed cSF-1 expression, with higher
      levels of expression in the left ovary compared to the right (regressing) gonad
      in females and compared to testes. RPA analysis of isolated gonads confirmed
      higher expression of SF-1 in differentiating ovaries relative to testes.
      Expression of cSF-1 in the developing adrenal gland was similar for both sexes at
      all stages examined. In tissue sections of day 8.5 whole mount gonads, cSF-1
      expression was localised in the medulla of the ovary and was weakly detectable in
      the testis. These observations indicate that SF-1 has a conserved role in early
      gonadal and adrenal development in vertebrates. However, upregulation of cSF-1
      expression during ovarian differentiation is opposite to the pattern seen in
      mammals, in which SF-1 is downregulated in females. This difference between the
      birds and mammals may reflect differences in steroidogenic activity of the
      embryonic ovary versus the testis in the two groups.

PMID- 10082622
TI  - Immunocytochemical study on the localization and distribution of the somatolactin
      cells in the pituitary gland and the brain of Oreochromis niloticus (Teleostei,
      cichlidae).
AB  - Using specific antibody for chum salmon somatolactin (SL), immunocytochemical
      studies were employed to determine the distribution of this hormone in the
      pituitary gland and the brain of Orechromis niloticus. The results indicated that
      the SL-immunoreactive (ir) cells are found in the pars intermedia (PI) of the
      pituitary gland. The SL-ir cells showed strong and specific immunoreactivity to
      anti-chum salmon SL. Moreover, SL-ir cells were found to be widely distributed in
      most brain regions. Most of the SL-ir cell bodies were scattered along a nearly
      continuous line extending posteriorly from the olfactory bulb to the medulla
      oblongata through the nucleus preopticus periventricularis, habenula, and
      midbrain tegmentum and ventral to the nucleus lateralis tuberis pars posterior
      through the nucleus preopticus basalis lateralis and organum vasculosum luminae
      terminalis. Also SL-ir cells were observed in the cerebellum. The synthetic and
      secretory activity of the SL-ir cells, in the pituitary and the brain, showed an
      increase during sexual maturation and spawning. The highly organized SL
      containing system and the gradual stimulation of SL synthesis and release during
      sexual maturation and spawning of O. nilotcus suggest that SL may be involved in
      the control of some steps of reproductive processes.

PMID- 10082623
TI  - Thyroid hormone regulation of perch ovarian 3beta-hydroxysteroid
      dehydrogenase/delta5-delta4-isomerase activity: involvement of a 52-kDa protein.
AB  - Ovarian follicles were collected from perch belonging to the prespawning
      (vitellogenic) stage and incubated in vitro for 5 h in the absence (control) and
      presence of 3, 5, 3'-triiodothyronine (T3). Addition of increasing concentrations
      of T3 from 12.5 to 100 ng/ml caused a linear increase of 3beta-hydroxysteroid
      dehydrogenase/delta5-delta4-isomerase (3 beta-HSD) activity to 50 ng and then it
      leveled off indicating a saturation of enzyme activity with 50 ng T3. T3
      stimulation of 3beta-HSD activity could be blocked by cycloheximide indicating
      the involvement of T3-induced protein (TIP) isolated and purified earlier from
      this laboratory. Addition of fish TIP purified from perch ovarian follicle (fTIP)
      or rat granulosa cell TIP to ovarian follicular incubation at a dose of 5
      microg/ml significantly increased (P < 0.01) 3beta-HSD activity. To observe
      whether TIP acts directly on the enzyme or not, 3beta-HSD from perch ovarian
      follicle was purified to homogeneity by the following steps: (i) Sephadex G 75
      gel filtration, (ii) DEAE-Sephacel chromatography, and (iii) NAD-affinity column
      chromatography. Purified 3beta-HSD gave a clear single band on an SDS gel and its
      molecular weight is 45 kDa. Addition of fTIP to an assay mixture containing
      purified 3beta-HSD resulted in a fourfold increase of the enzyme activity. fTIP
      alone did not show enzyme activity when incubated with the radiolabeled
      substrate. Addition of T3 (50 ng) to the 3beta-HSD assay mixture had no effect on
      the enzyme activity. Determination of Vmax and Km of the purified enzyme in the
      absence (control) and presence of fTIP demonstrated a considerable increase of
      3beta-HSD affinity and rate of enzyme reaction.

PMID- 10082624
TI  - Effects of the aromatase inhibitor Fadrozole on plasma sex steroid secretion and
      ovulation rate in female coho salmon, Oncorhynchus kisutch, close to final
      maturation.
AB  - Plasma levels of 17beta-estradiol, 17alpha, 20beta-dihydroxy-4-pregnen-3-one
      (17alpha,20beta-P), and testosterone were measured in adult female coho salmon in
      late vitellogenesis, approximately 1.5 months before spawning and just before and
      following intraperitoneal injection with the aromatase inhibitor (AI) Fadrozole.
      Injection at dosages of 0.1, 1.0, and 10.0 mg AI/kg body wt caused a significant
      drop in plasma 17beta-estradiol levels relative to preinjection values within 3
      or 6 h. Injection of 10 mg AI/kg body wt caused a significant increase in plasma
      17alpha-20beta-P levels within 3 h. Ten days after injection 67% of the fish
      treated with 10 mg AI/kg body wt had ovulated in contrast with 0% in the group
      injected with 0.1 mg AI/kg body wt. The fertilization rate of the eggs varied
      between 96% in the control group and 85% in the groups injected with AI. We
      conclude that the shift from 17beta-estradiol to 17alpha,20beta-P biosynthesis,
      which is characteristic of maturing Oncorhynchus sp., was advanced significantly
      by treatment with AI and that Fadrozole can be used as a tool to investigate
      periovulatory endocrine changes in salmon.

PMID- 10082625
TI  - Inhibition of S6 kinase by rapamycin blocks maturation of Rana dybowskii oocytes.
AB  - Studies were carried out to define the hormone-induced signal transduction
      pathway during maturation of Rana dybowskii oocytes. Rapamycin, a specific
      inhibitor of S6 kinase, blocked progesterone-induced oocyte germinal vesicle
      breakdown (GVBD) in a dose-dependent manner indicating that S6 kinase is required
      for meiotic maturation of Rana oocytes. Addition of rapamycin within 3 h, but not
      6 h, of progesterone treatment inhibited GVBD. In contrast, cycloheximide, a
      general protein synthesis inhibitor, blocked GVBD even when added 9 h after
      progesterone addition. A twofold increase in S6 kinase activity occurred within 1
      h of progesterone stimulation and rapamycin inhibited this activity. Rapamycin
      also suppressed, in a dose-dependent manner, progesterone-induced protein
      synthesis during the first 12 h of culture but less effectively later. Histone H1
      kinase activity (maturation-promoting factor, MPF) was observed in oocyte
      extracts at two different times (between 6 and 9 h and at 24 h) following
      progesterone stimulation. Rapamycin blocked H1 kinase activity between 6 and 9 h
      of culture but not that observed at 24 h. In contrast, cycloheximide suppressed
      progesterone-induced H1 kinase activity as well as protein synthesis throughout
      the course of incubation. Such results indicate that rapamycin and cycloheximide
      have common and unique effects on oocyte maturation and suggest that progesterone
      induced S6 kinase activity is closely associated with induction of protein
      synthesis and activation of MPF during oocyte maturation. Results in Rana
      contrast with those obtained in Xenopus where rapamycin inhibited S6 kinase but
      failed to inhibit GVBD or protein synthesis. Differences in the response of Rana
      and Xenopus oocytes to rapamycin are discussed in relation to seasonal,
      biochemical, and species variations.

PMID- 10082626
TI  - The effect of photoperiod on diel rhythms in serum melatonin, cortisol, glucose,
      and electrolytes in the common dentex, Dentex dentex.
AB  - Diel rhythms in serum concentrations of melatonin, cortisol, glucose, sodium,
      chloride, and potassium were studied in the common dentex, Dentex dentex, under
      different photoperiods (DD, 8L:16D, 12L:12D, 16L:8D). Photoperiod affected both
      the diel rhythms and the absolute values of the estimated blood components.
      Regardless of the photoperiod, melatonin titers were elevated during the
      scotophase (384.3 +/- 13.9 pg/ml) compared with a mean baseline level of 54.4 +/-
      2.7 pg/ml during the photophase. Serum melatonin concentrations reflected the
      prevailing photoperiod and constantly elevated melatonin levels with no diel
      rhythmicity were evident in fish held in the DD protocol. A circadian-like
      pattern in serum cortisol was observed in fish that were kept at the DD and
      8L:16D protocols with cortisol peak at 18:00 h in the night. Fish exposed to the
      16L:8D regime showed highest cortisol levels at 10:00 h, while no rhythmicity was
      evident under the 12L:12D protocol. A phase shift of 4 h between the peaks of
      cortisol and glucose was evident in fish exposed to the DD, 8L:16D, and 12L:12D
      regimes. Diel patterns of changes in serum Na+ and Cl- were observed only in the
      fish held in the DD protocol. Serum K+ values were lowest during the first part
      of the scotophase under all regimes, except the 16L:8D where no diel rhythmicity
      was detected. During the photophase, cortisol was positively correlated with
      glucose, Na+, and Cl- and negatively with K+. During the scotophase, melatonin
      was positively correlated with glucose and electrolytes. Results indicated that
      cortisol may be responsible for the observed rhythmicity of glucose and that
      melatonin may play a role in glucose and ion regulation in common dentex.

PMID- 10082627
TI  - A brain-Hatschek's pit connection in amphioxus.
AB  - In the adult lancelet, Branchiostoma belcheri, there is a lobe of the right
      ventral margin of the brain that extends around the right side of the notochord
      and makes contact with Hatschek's pit, which also is to the right of the midline.
      This structural system resembles the hypothalamo-adenohypophyseal system of
      vertebrates and appears to make possible seasonal nervous regulation of the
      release of gonadotropin.

PMID- 10082628
TI  - Dietary protein restriction stress in the domestic fowl (Gallus gallus
      domesticus) alters adrenocorticotropin-transmembranous signaling and
      corticosterone negative feedback in adrenal steroidogenic cells.
AB  - Previous work with growing chickens (Gallus gallus domesticus) indicates that
      transient dietary protein restriction induces long-term enhancement of adrenal
      steroidogenic function in response to adrenocorticotropin (ACTH). The present
      study investigated two possible cellular functions mediating this enhanced
      response: (a) ACTH signal transduction and dissemination and (b) short-loop
      feedback inhibition of ACTH-induced corticosterone production by exogenous
      corticosterone. Cockerels (2 weeks old) were fed isocaloric synthetic diets
      containing either 20% (control) or 8% (restriction) soy protein for 4 weeks.
      Adrenal glands were processed for the isolation of adrenal steroidogenic cells
      nearly devoid of chromaffin cells ( approximately 90% adrenal steroidogenic
      cells). Results of experiments to assess signal transduction and dissemination
      indicated that protein restriction selectively enhanced ACTH-induced
      corticosterone production mediated by the cyclic AMP (cAMP)-dependent pathway. In
      addition, protein restriction substantially counteracted exogenous corticosterone
      dependent inhibition of acute ACTH-induced corticosterone production (by 40.7% vs
      control). The proximal portion of the cAMP pathway seemed most affected by this
      stressor. Protein-restricted cells exhibited enhanced homologous sensitization to
      ACTH (136% greater than that of control cells) which appeared to be localized at
      a step(s) prior to or at the formation to cAMP. Also, maximal ACTH-induced cAMP
      production and sensitivity to ACTH in terms of cAMP production by protein
      restricted cells were, respectively, 2.2 and 15.8 times those of control cells.
      However, variable results were obtained from other experiments designed to
      pinpoint the altered early steps in ACTH-transmembranous signaling. For example,
      with intact cells, cAMP responses to cholera toxin (CT) and forskolin (FSK) did
      not corroborate the results suggesting an augmentation of ACTH-signal
      transduction induced by protein restriction. Furthermore, basal and stimulatable
      (by ACTH, CT, FSK, and NaF) adenylyl cyclase activities from membranes from
      protein-restricted cells were, respectively, 47.2 and 40.2% less than those from
      control cells (normalized to 10(7) cell equivalents of crude membranes).
      Collectively, these findings suggest that protein restriction stress potentiates
      ACTH-induced corticosterone secretion by chicken adrenal steroidogenic cells in
      at least two ways: (1) on the proximal end, by modulating unknown factors which
      enhance cellular sensitivity to ACTH, ACTH receptor-adenylyl cyclase coupling,
      and adenylyl cyclase activity, and (2) on the distal end, by suppressing end
      product corticosterone negative feedback, thus facilitating an increase in net
      corticosterone secretion.

PMID- 10082629
TI  - Calcitonin cells in the intestine of goldfish and a comparison of the number of
      cells among saline-fed, soup-fed, or high Ca soup-fed fishes.
AB  - Calcitonin-immunoreactive cells were found in the intestine of goldfish. These
      cells were distributed mainly in the anterior part of the intestine, dispersed in
      the intestinal epithelium. The nucleus was located in the basal portion of the
      serosal side, and the cytoplasm was elongated to the luminal side. From the
      anterior part of the intestine, cDNA fragments with the same nucleotide sequence
      as that of the goldfish calcitonin gene were amplified by RT-PCR method. After
      administration of one of three kinds of solutions (saline, consomme soup, or high
      Ca consomme soup) into the digestive tract of the goldfish, the number of those
      cells was the largest in the consomme group at 6 h after ingestion, although
      blood Ca levels were the highest in the high Ca consomme group. The function of
      calcitonin cells in the intestine may be to restrain the acute absorption of
      nutrients and not to control blood Ca levels.

PMID- 10082630
TI  - Multiple forms of glucagon and somatostatin isolated from the intestine of the
      southern-hemisphere lamprey Geotria australis.
AB  - Current views on Agnathan phylogeny favor the hypothesis that the genera of
      holarctic lampreys belong to a single family (Petromyzontidae) and form an
      interrelated progression in which Petromyzon is near to Ichthomyzon at the base
      of the phylogenetic tree and Lampetra is the most derived. A stock similar to
      that of contemporary Ichthomyzon is considered to have given rise to the southern
      hemisphere lamprey Geotria australis, the sole member of the Geotriidae. In the
      present study, two molecular forms of glucagon were isolated from an extract of
      G. australis intestine that differed in structure by six amino acid residues. One
      form shows two amino acid substitutions (Leu14 --> Met and Ala29 --> Ser)
      compared with the single molecular form of glucagon isolated from the sea lamprey
      Petromyzon marinus and the second form shows three substitutions (Asp15 --> Glu,
      Ser16 --> Ala, Ile24 --> Thr) compared with the single glucagon isolated from the
      river lamprey Lampetra fluviatilis. As Petromyzon and Lampetra glucagons differ
      by six amino acid residues, the data suggest that a duplication of the glucagon
      gene occurred prior to or early in lamprey evolution. Although both genes are
      strongly expressed in G. australis, the expression of one gene predominates in P.
      marinus while that of the other gene predominates in L. fluviatilis. Previous
      work has shown that, in the islet organ of G. australis, preprosomatostatin is
      processed almost exclusively to somatostatin-33. However, the present study
      demonstrates that somatostatin-14 is the major molecular form in G. australis
      intestine with somatostatin-33 present only as a minor component. This result
      demonstrates a tissue-dependent pathway of posttranslational processing of
      preprosomatostatin in the Geotria enteropancreatic system.

PMID- 10082631
TI  - Generation of chicken growth hormone-binding proteins by proteolysis.
AB  - A soluble protein that specifically bound growth hormone (GH) was characterized
      in culture medium of a COS-7 cell line transfected with the cDNA of the full
      length chicken GH receptor (cGHR). Incubation of culture medium with 125I-labeled
      human GH resulted in the formation of a single specific complex with high
      affinity (KD = 0.36 nM) and apparent molecular weight of 75 kDa. The production
      of large quantities of GH-binding protein (GHBP) amounting to, per hour, 23% of
      the cell's GHR, points to the importance of partial proteolysis for GHR turnover.
      Considerable amounts of GHBP were also detected in a cytosolic fraction. These
      results strongly suggest that in chicken, as in rabbit and monkey, the GHBP is
      generated, at least partially, by proteolytic cleavage of the membrane-anchored
      GHR.

PMID- 10082632
TI  - Beta-endorphin-like immunoreactivity in the forebrain and pituitary of the
      teleost Clarias batrachus (Linn.).
AB  - The organization of beta-endorphin-like immunoreactivity in the olfactory system,
      forebrain, and pituitary of the teleost Clarias batrachus was investigated.
      Immunoreactivity was prominently seen in the sensory neurons and basal cells in
      the olfactory epithelium and in some cells in the periphery and center (granule
      cells) of the olfactory bulb. Immunoreactive fibers in the olfactory nerve enter
      the olfactory nerve layer of the olfactory bulb and branch profusely to form
      tufts organized as spherical neuropils in the glomerular layer. While fascicles
      of immunoreactive fibers were seen in the medial olfactory tracts, the lateral
      olfactory tracts showed individual immunoreactive fibers. Immunoreactive fibers
      in the medial olfactory tract extend into the telencephalon and form terminal
      fields in discrete telencephalic and preoptic areas; some immunoreactive fibers
      decussate in the anterior commissure, while others pass into the thalamus. While
      neurons of the nucleus lateralis tuberis revealed weak immunoreactivity, densely
      staining somata were seen at discrete sites along the wall of the third
      ventricle. Although a large population of immunoreactive cells was seen in the
      pars intermedia of the pituitary gland, few were seen in the rostral pars
      distalis and proximal pars distalis; immunoreactive fibers were seen throughout
      the pituitary gland.

PMID- 10082633
TI  - Elevation of plasma prolactin concentrations by low temperature is the cause of
      spermatogonial cell death in the newt, Cynops pyrrhogaster.
AB  - Temperature plays an important role in reproduction of urodeles. Spermatogenesis
      in newts is arrested when the environmental temperature lowers. We found that
      transfer of newts, Cynops pyrrhogaster, to low temperature (8 and 12 degrees C)
      caused cell death of spermatogonia just before meiosis and elevation of prolactin
      concentration in the newt plasma. Injection of a dopamine antagonist (pimozide),
      which is known to increase the plasma prolactin concentration, to the newt caused
      significant increase of spermatogonial degeneration, whereas treatment with an
      agonist (bromocryptin), which is known to decrease the prolactin concentration,
      suppressed the cell death. Finally, injection of anti-prolactin serum into the
      newts which had been transferred to low temperature almost completely inhibited
      the spermatogonial degeneration for as long as 3 days. These results demonstrate
      that low temperature caused elevation of prolactin concentration in the newt
      blood, which induced cell death of spermatogonia just before meiosis.

PMID- 10082634
TI  - Angiotensin II-induced calcium signalling in isolated glomeruli from fish kidney
      (Oncorhynchus mykiss) and effects of losartan.
AB  - Glomeruli were isolated from the kidney of freshwater-adapted rainbow trout,
      Oncorhynchus mykiss, to qualitatively evaluate changes in cellular calcium
      associated with angiotensin II ([Asn1Val5]-Ang II) receptor stimulation and
      antagonism by the Ang II receptor antagonist losartan. Microspectrofluorometry
      using the fluorescent calcium indicator dye Calcium Green recorded fluorescence
      changes in isolated single glomeruli. Isolated glomeruli containing ester-loaded
      Calcium Green showed an Ang-II-induced transient rise in fluorescence. This
      transient rise showed an increased peak amplitude with increased Ang II
      concentration (10(-9) to 10(-6) M), but only a very small response was detectable
      in glomeruli exposed to 10(-9) M Ang II. The biphenylimidazole compound losartan
      (=DuP 753), an antagonist of the mammalian AT1 subtype Ang II receptor, initiated
      a transient agonistic rise in glomerular fluorescence at high concentration (10(
      5), 10(-4), and 10(-3) M). However, the responses to 10(-6) 10(-7) M losartan
      were small or very low in each case. Losartan (10(-4) or 10(-7) M) antagonised
      the Ang-II-induced signalling in isolated glomeruli exposed to 10(-7) or 10(-6) M
      Ang II, respectively. This is the first evidence for functional AT1-like Ang II
      receptors coupled to cellular calcium signalling in the glomeruli of rainbow
      trout.

PMID- 10082635
TI  - The amygdala is involved in the modulation of long-term memory, but not in
      working or short-term memory.
AB  - Rats with cannulae implanted in the junction between the central and the
      basolateral nuclei of the amygdala were trained in one-trial step-down inhibitory
      avoidance and tested at 3 s for working memory (WM) or 1.5 or 24 h later for
      short-term memory (STM) and long-term memory (LTM), respectively. Several drugs
      were infused 6 min prior to training in the animals in which WM was measured or 0
      min posttraining in those in which STM and LTM were measured: the glutamate
      receptor antagonists CNQX (0.5 microg) and AP5 (5.0 microg), the indirect GABA A
      receptor antagonist picrotoxin (0.08 microg), the cholinergic muscarinic receptor
      blocker scopolamine (2. 0 microg), norepinephrine (0.3 microg), the protein
      kinase C inhibitor staurosporin (1.0 microg), or the calcium/calmodulin dependent
      protein kinase II inhibitor Kn-62 (3.5 ng). None of the drugs had any effect on
      either WM or STM. All had, as previously shown, strong effects on LTM: picrotoxin
      and norepinephrine enhanced it, and CNQX, AP5, scopolamine, Kn-62, and
      staurosporin inhibited it. The results do not support the idea that memory of
      this task is formed in the amygdala; they indicate that the amygdala is not
      involved in WM or STM processing and support the idea that the amygdala modulates
      LTM storage processes carried out elsewhere.

PMID- 10082636
TI  - Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor
      activity of rats: short- and long-term study.
AB  - The effects of 14-day treatments with nerve growth factor (NGF), basic fibroblast
      growth factor (b-FGF), or the peptidergic drug Cerebrolysin on postlesion
      acquisition of a water maze task and on motor activity were evaluated. Rats were
      tested in the Morris water maze 14 days (early test) and 7 to 8 months (delayed
      test) after a bilateral lesion of the frontoparietal (sensorimotor) cortex. Only
      the rats treated with Cerebrolysin performed the water maze task at the level of
      the nonlesioned controls in the early test. No short-term effect of NGF (6.5
      ng/14 days; 38 ng/ml) or b-FGF (17 ng/14 days; 100 ng/ml) treatment was found.
      The delayed test revealed that water maze performance was restored in rats
      treated with b-FGF in comparison with intact controls. The data showed that b-FGF
      can support or initiate processes in the CNS that lead to a delayed functional
      amelioration and/or compensation for a water maze performance deficit. NGF did
      not influence the acquisition impairment caused by a sensorimotor cortical
      lesion. Two-week administration of Cerebrolysin had a time-dependent influence:
      it attenuated the acquisition deficit and increased the motor activity of rats,
      both effects declined to the level of lesioned controls within 8 months.

PMID- 10082637
TI  - Pavlovian heart rate and jaw movement conditioning in the rabbit: effects of
      medial prefrontal lesions.
AB  - An experiment was conducted in which jaw movements (JM) and heart rate (HR) were
      concomitantly assessed in rabbits during simple Pavlovian conditioning. A 2-s
      1200-Hz tone was the conditioned stimulus (CS) and an intraoral 1-cc pulse of 0.5
      M sucrose-water solution was the unconditioned stimulus (US). Sham and medial
      prefrontal (mPFC)-lesioned animals received paired CS/US training with a 70- to
      75-dB CS and were compared with sham- and mPFC-lesioned animals that received
      explicitly unpaired CS/US presentations. The percentages of JM CRs were
      significantly greater in the paired than the unpaired groups, but mPFC lesions
      had no effect on this measure. Conditioned HR decelerations occurred only in the
      paired groups and then only during the first session of training. Moreover, these
      CS-evoked cardiac decelerations were somewhat attenuated by the mPFC lesion. CS
      evoked HR accelerations, which were significantly greater in unpaired than in
      paired animals, occurred during the four subsequent sessions. These results
      suggest that a CS-evoked cardioinhibitory process, mediated by the mPFC, is
      engendered by Pavlovian appetitive conditioning, as has been previously
      demonstrated for aversive conditioning. However, during JM conditioning these
      inhibitory changes are quickly replaced by tachycardia, possibly related to
      increased nonspecific somatomotor activity, since the tachycardia was somewhat
      greater in the unpaired animals.

PMID- 10082638
TI  - Essential neuronal pathways for reflex and conditioned response initiation in an
      intracerebellar stimulation paradigm and the impact of unconditioned stimulus
      preexposure on learning rate.
AB  - It has been demonstrated previously that pairing of tone CS and intracerebellar
      stimulation of lobule HVI white matter as the US produces conditioning that is
      robust and in many ways similar to that obtained with an airpuff US. The first
      study in this report addressed the effect of interpositus lesions on conditioned
      performance in rabbits trained with white matter stimulation as the US. It was
      found that interpositus lesions effectively eliminated the CR irrespective of the
      behavioral response measured. In addition, it was shown that the interpositus
      lesions also abolished the UR, providing strong evidence that the effects of the
      electrical stimulation were confined to the cerebellum and did not require the
      activation of brainstem structures. The second experiment examined performance on
      US-alone trials of varying durations. Response initiation within 100 ms of the US
      onset, regardless of US duration, indicated that reflex generation could not be
      due to rebound excitation of the interpositus following termination of Purkinje
      cell inhibition of that structure but instead likely reflects orthodromic
      activation of interpositus neurons via climbing fiber and/or mossy fiber
      collaterals. The impact of US preexposure on associative conditioning in this
      paradigm was also determined. Animals which received only 108 US-alone trials
      were massively impaired during subsequent training compared to rabbits that
      received fewer than 12 US-alone trials.

PMID- 10082639
TI  - MK-801 improves retention in aged rats: implications for altered neural
      plasticity in age-related memory deficits.
AB  - Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic
      plasticity, characteristic of aged rodents, may contribute to impaired memory
      with advanced age. The purpose of the current research was to examine whether
      NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24
      months) and adult (3-6 months) male Fischer 344 rats received 18 training trials,
      over a period of 3 to 4 h, on the spatial version of the Morris water maze.
      Immediately after training, a standard free-swim probe trial was administered to
      assess the acquisition of spatial bias, which was determined by the percent of
      time spent in the goal quadrant and the number of platform crossings. Rats then
      received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro
      5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a
      vehicle injection of equal volume. Approximately 24 h later, rats were
      administered a second free-swim probe trial to assess retention of spatial bias.
      All age/drug groups exhibited a spatial bias on the acquisition probe, with
      adults generally outperforming the aged rats. On the retention probe, this
      spatial bias continued to be shown by adult rats, regardless of treatment. For
      the aged group, in contrast, only MK-801-injected rats maintained a spatial bias
      on the retention probe, suggesting that NMDAR activity may be involved in rapid
      forgetting during aging. Because blockade of NMDARs also may impair new learning,
      which may, in turn, protect previously stored information from retroactive
      interference, rats in a second experiment received post-training injections of
      scopolamine (0.05 mg/kg), a compound known to inhibit learning. However,
      scopolamine did not enhance retention in the aged group, consistent with the
      hypothesis that MK-801 influenced memory in aged rats through its actions on
      NMDAR-dependent synaptic plasticity.

PMID- 10082640
TI  - 5-HT1A receptors modulate the consolidation of learning in normal and cognitively
      impaired rats.
AB  - Attempts were made to further analyze the role of 5-HT1A receptors in
      consolidation of learning by evaluating the role of these receptors in
      cognitively normal and impaired animals. The effects of post-training
      administration of 8-OH-DPAT and 5-HT1A receptor antagonists, WAY 100135, WAY
      100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists,
      scopolamine and dizolcipine, respectively, were determined using an autoshaping
      learning task. The results showed that 8-OH-DPAT increased the number of
      conditioned responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT
      depleter, p-chloroamphetamine (PCA), had no effect. PCA did not change the silent
      properties of the 5-HT1A receptor antagonists. PCA, WAY100635, and S-UH-301, but
      not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-HT2A receptor
      antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5-HT2A/2C receptor
      antagonist) and ondansetron (a 5-HT3 receptor antagonist), at a dose that
      increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT.
      Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by
      scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine
      only. These data confirm a role for presynaptic 5-HT1A receptors during the
      consolidation of learning and support the hypothesis that serotonergic,
      cholinergic, and glutamatergic systems interact in cognitively impaired animals.

PMID- 10082641
TI  - Inhibition of nitric oxide synthase impairs early olfactory associative learning
      in newborn rats.
AB  - The present experiments examined the role of nitric oxide ( NO) in early
      associative olfactory learning in rats. A preference for peppermint odor was
      induced by pairing peppermint odor with tactile stimulation in Wistar rat pups,
      in either a repetitive training paradigm or in a one-trial olfactory learning
      paradigm. In a first experiment we studied the effect of nitric oxide synthase
      (NOs) inhibition on early olfactory learning in a repetitive paradigm, by
      systemic daily injections of NG-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg,
      i.p.). In order to exclude possible deleterous effects of repeated injections of
      l-NAME, we explored in a second experiment the effect of a single inhibitor
      injection in a one-trial olfactory learning paradigm. Inhibition of NOs was
      performed by either administration of l-NAME (50 mg/kg, i.p.), or 7-nitroindazole
      (7-NI, 30 mg/kg, i.p.), a more selective inhibitor of the neuronal NOs. We showed
      that both l-NAME and 7-NI impaired early olfactory associative learning when
      given before training but not before subsequent testing. Considering that NOs
      neurons are already widespread in the central nervous system (the olfactory bulb
      included) during the first postnatal week, the sites where NO inhibition may have
      acted to impair olfactory learning are discussed. The mechanisms of action of NO
      in relation with other neurotransmitters known to be necessary for olfactory
      conditioning in rat pups remain to be established. Impairment by NO synthesis
      inhibition of the acquisition during the first postnatal week of an olfactory
      conditioning, but not its recall, suggests a role for NO at synapses involved in
      that learning.

PMID- 10082642
TI  - Norepinephrine infused into the basolateral amygdala posttraining enhances
      retention in a spatial water maze task.
AB  - Recent evidence indicates that the amygdala plays a role in modulating memory
      processes in other brain regions. For example, posttraining intra-amygdala
      infusions of amphetamine enhanced memory in both spatial and cued training water
      maze tasks; these tasks are known to depend on the integrity of the hippocampus
      and caudate nucleus, respectively. To determine whether this modulation is
      dependent on noradrenergic activation within a subregion of the amygdala (the
      basolateral nucleus), the present study examined the effects of posttraining
      microinfusions (0.2 microl) of norepinephrine or propranolol into the basolateral
      amygdala immediately following training in a spatial version of the water maze
      task. Rats received a four-trial training session on each of 2 consecutive days.
      On the third day, rats were given a 60-s probe test in the absence of a platform.
      Retention latencies obtained on the second training day revealed that
      norepinephrine dose-dependently enhanced retention for the location of the hidden
      platform. In contrast, propranolol significantly impaired retention. Probe trial
      analysis revealed that rats treated with 0.25 microg norepinephrine demonstrated
      a selective spatial bias for the training platform location relative to all other
      groups. These findings are consistent with others and support the view that the
      basolateral amygdala has a role in modulating memory storage by interacting with
      other brain regions.

PMID- 10082643
TI  - Involvement of the posteroventral caudate-putamen in memory consolidation in the
      Morris water maze.
AB  - Male Sprague-Dawley rats implanted with bilateral intracerebral guide cannulae
      were trained in the standard hidden platform version of the Morris water maze and
      given immediate posttraining infusions of the D2 dopamine receptor antagonist
      sulpiride (10.0 or 100.0 ng/side) or saline vehicle into the posteroventral
      caudate-putamen. Retention was tested 2 days later with a probe trial. Sulpiride
      treated rats spent less time swimming near the trained platform location and more
      time in the periphery of the maze than controls, although their latency to reach
      the trained platform location was not significantly affected. The pattern of
      results suggests that whereas the posteroventral caudate-putamen seems to be
      involved in consolidation of memory in the Morris water maze, it may be involved
      in memory for procedural aspects of the task in a manner distinct from that of
      other brain regions such as the hippocampus.

PMID- 10082644
TI  - Chronic administration of propranolol impairs inhibitory avoidance retention in
      mice.
AB  - Adrenergic systems are importantly involved in memory storage processes. As such,
      agents that alter adrenergic receptors, such as "beta-blockers," also alter
      memory storage. However, the anxiety literature cautions that beta-adrenergic
      receptor antagonists, such as propranolol, may have different behavioral effects
      with acute vs chronic dosing. The effects of chronic propranolol specifically on
      memory modulation are unknown. This study was designed to evaluate the effects of
      chronic propranolol on retention for an aversive task, in which there is
      endogenous adrenergic activation. Adult male ICR mice were given daily injections
      of one of four doses of propranolol (2, 4, 8, and 12 mg/kg) or 0.9% NaCl vehicle
      for 15 days prior to, and continuing during, behavioral tests of exploration and
      retention. Exploratory behavior, as an index of anxiety level, was measured in a
      conventional elevated plus-maze, whereas retention of an aversive experience was
      measured in a step-through inhibitory avoidance apparatus. Sensitivity to
      aversive footshock was also evaluated. Compared to controls, propranolol-treated
      mice showed a dose-dependent decrease in retention for the inhibitory avoidance
      task, but no effect on anxiety on the plus-maze or on footshock sensitivity.
      Taken together with results from previous studies, it is apparent that
      propranolol can have different behavioral effects when administered acutely vs
      chronically, and its chronic effects significantly impair memory storage
      processes. Since these drugs are typically used chronically, and often in older
      adults, they could contribute to functional memory impairments.

PMID- 10082645
TI  - R-Loop in the replication origin of human mitochondrial DNA is resolved by RecG,
      a Holliday junction-specific helicase.
AB  - Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in
      Escherichia coli cells. The R-loops are resolved by Escherichia coli RecG
      protein, a Holliday junction specific helicase. A stable RNA-DNA hybrid formation
      in the mitochondrial D-loop region is also implicated in priming the replication
      of mitochondrial DNA. Consistent with this hypothesis, the 3' ends of the
      mitochondrial R-loop formed by in vitro transcription are located close to the
      initiation sites of the mitochondrial DNA replication. This mitochondrial R-loop
      is resolved by RecG in a dose-dependent manner. Since the resolution by RecG
      requires ATP, the resolution is dependent on the helicase activity of RecG. A
      linear RNA-DNA heteroduplex is not resolved by RecG, suggesting that RecG
      specifically recognizes the higher structure of the mitochondrial R-loop. This is
      the first example that R-loops of an eukaryotic origin is sensitive to a junction
      specific helicase. The resolution of the mitochondrial R-loop by RecG suggests
      that the replication-priming R-loops have a common structural feature recognized
      by RecG.

PMID- 10082646
TI  - A comparative study of apoptosis and necrosis in HepG2 cells: oxidant-induced
      caspase inactivation leads to necrosis.
AB  - Apoptosis and necrosis are two distinct forms of cell death that can occur in
      response to various agents. In the present study the HepG2 cell line was used for
      a comparative study of CD95-mediated apoptosis and menadione-induced necrosis.
      Apoptosis coincided with the release of cytochrome c from mitochondria,
      activation of caspases, cleavage of cellular proteins, and also involved nuclear
      condensation and DNA fragmentation. Necrosis was not accompanied by DNA
      fragmentation, caspase activation or cleavage of caspase target proteins, despite
      cytochrome c release from mitochondria. In fact, the addition of menadione to
      cells undergoing CD95-mediated apoptosis blocked their caspase activity.
      Inhibition of caspases coincided with an accumulation of reactive oxygen species
      (ROS) and ATP depletion. In order to determine the predominance of either of
      these events in the inhibition of caspase, cells were either co-incubated with
      antioxidant enzymes or their ATP level was manipulated to maintain it at a
      relatively high level during the experiments. Co-incubation with catalase, but
      not Cu/Zn superoxide dismutase, substantially reduced the levels of ROS and
      reversed the inhibitory effect of menadione on caspase activity. In contrast,
      increasing cellular ATP level had little effect on restoring caspase activity.
      These data suggest that menadione inhibits caspase activity by the generation of
      hydrogen peroxide through redox cycling and that caspase inactivation by this
      mechanism may prevent cell death by apoptosis in this oxidative-stress model.

PMID- 10082647
TI  - Signal transduction in rat vascular smooth muscle cells: control of osmotically
      induced aldose reductase expression by cell kinases and phosphatases.
AB  - We have studied the osmotically induced gene expression (measured as
      chloramphenicol acetyl transferase (CAT) reporter gene expression) in rat smooth
      muscle cell primary cultures (rSMC), under the control of osmotic response
      elements (ORE). It was found that osmotically induced gene expression is
      sensitive to signal transduction inhibitors and activators. In particular,
      protein kinase C inhibition by calphostin C prevented gene expression by osmotic
      response. On the other hand, receptor tyrosine kinase inhibition has been shown
      to produce an enhancement of gene expression. This suggests that tyrosine kinase
      receptor activation exerts an inhibitory action on ORE induced gene expression.
      Gene expression was also induced by treating cells with PD098059, a specific
      inhibitor of mitogen-activated protein kinase kinase. Moreover, the same
      inhibitors and activators have been shown to affect the hyperosmosis induced
      expression of aldose reductase gene.

PMID- 10082648
TI  - Refolding of thioredoxin reductase assisted by groEL and PDI.
AB  - Thioredoxin reductase was unfolded in 2 M guanidine hydrochloride as revealed by
      fluorescence and CD spectroscopy. Spontaneous refolding of denatured species
      resulted in low recovery of 10% catalytic activity after 4 h incubation at 25
      degrees C. Addition of groEL or protein disulfide isomerase to the renaturation
      buffer accelerated the rate of recovery of catalytic activity to a level of 35
      and 15%, respectively. Fluorescence spectroscopy has been used to investigate the
      interaction of groEL and protein disulfide isomerase with denatured thioredoxin
      reductase tagged with a fluorescent probe. The fluorescence emitted by the
      denatured protein was quenched upon binding to either groEL or protein disulfide
      isomerase. It is suggested that encapsulation of the protein substrate by the
      chaperone plays an important role in the process of folding by facilitating the
      formation of correctly folded species.

PMID- 10082649
TI  - Stimulation of tyrosine phosphorylation by progesterone and its 11-OH
      derivatives: dissection of a Ca(2+)-dependent and a Ca(2+)-independent mechanism.
AB  - Progesterone has previously been shown to exert non-genomic effects on human
      spermatozoa by opening plasma membrane ion channels and by stimulating protein
      tyrosine phosphorylation. Here we examined how these two activities are
      influenced by 11-hydroxyl substitution of the steroid molecule either in the
      alpha- or in the beta-configuration. Both the 11alpha-OH and the 11beta-OH
      derivatives of progesterone were more effective than progesterone in stimulating
      tyrosine phosphorylation, although 11alpha-OH-progesterone was a markedly weaker
      Ca(2+)-influx inducing agonist than the other two steroids. In Ca(2+)-containing
      medium, the agonist activity of the 11alpha-OH derivative was weaker than that of
      the 11beta-OH derivative, and it was completely abolished by genistein, whereas
      that of progesterone and its 11beta-OH derivative was inhibited only partly by
      this drug. In contrast, when applied in Ca(2+)-free medium, the 11alpha-OH
      derivative was the strongest of the three agonists tested, and the effects of all
      the three steroids were completely abolished by genistein. These data show that
      the structural motifs of steroid molecules that are responsible for the
      stimulation of tyrosine phosphorylation are different from those mediating the
      steroid action on Ca2+ influx through plasma membrane channels. The synthesis of
      selective agonists of both activities may lead to the development of new
      pharmacological agents to be used in the treatment of steroid-dependent
      pathologies.

PMID- 10082650
TI  - Three steroidogenic factor-1 binding elements are required for constitutive and
      cAMP-regulated expression of the human adrenocorticotropin receptor gene.
AB  - In the present study, we characterized two new SF-1 binding sites, SF-209 and SF
      98, in the promoter of the human ACTH receptor (hACTH-R) gene. Both sites,
      together with the previously described SF-35 site, are required for full
      constitutive activity of this gene. This was demonstrated by the use of
      constructs containing part of the promoter upstream of the luciferase gene and
      carrying mutation in one of these sites, to transiently transfect H295R cells.
      Mutations of either SF-35, SF-98, or SF-209 induced a decrease of luciferase
      activity. This effect was amplified when two or three elements were mutated
      together in the same construct. Only SF-35 and SF-98 seem to play a major role in
      the cAMP-induced regulation of the hACTH-R gene, since mutation of either one of
      these sites reduced the forskolin induction of luciferase activity by 50%. When
      both elements were mutated, no stimulation was obtained over the control. This
      indicates that SF-1 protein must bind to both sites for the cAMP response.

PMID- 10082651
TI  - Identification of caveolin-1 as a fatty acid binding protein.
AB  - In an attempt to identify high affinity, fatty acid binding proteins present in
      3T3-L1 adipocytes plasma membranes, we labeled proteins in purified plasma
      membranes with the photoreactive fatty acid analogue, 11-m-diazirinophenoxy[11
      3H]undecanoate. A single membrane protein of 22 kDa was covalently labeled after
      photolysis. This protein fractionated with caveolin-1 containing caveolae and was
      immunoprecipitated by an anti-caveolin-1 monoclonal antibody. Furthermore, 2D
      PAGE analysis revealed that both the alpha and beta isoforms of caveolin-1 could
      be labeled by the photoreactive fatty acid upon photolysis, indicating that both
      bind fatty acids. The saturable binding of the photoreactive fatty acid suggests
      caveolin-1 has a lipid binding site that may either operate during intracellular
      lipid traffic or regulate caveolin-1 function.

PMID- 10082652
TI  - Functional organization of the human uncoupling protein-2 gene, and juxtaposition
      to the uncoupling protein-3 gene.
AB  - Human and mouse UCP2 genes were cloned and sequenced. Transcriptional start sites
      were identified using primer extension analysis. The transcription unit of UCP2
      gene is made of 2 untranslated exons followed by 6 exons encoding UCP2. In vitro
      translation analysis demonstrated that an open-reading-frame for a putative
      peptide of 36 residues present in exon 2 did not prevent UCP2 translation and
      confirmed that the initiation site of translation was in exon 3 as predicted from
      sequencing data. Short (bp -125 to +93) and long (bp -1383 and +93) CAT
      constructs containing DNA upstream of the transcriptional start site of the human
      gene were made and transfected in adipocytes or HeLa cells allowing
      characterization of a potent promoter. Analysis of several genomic clones
      encompassing UCP2 and/or UCP3 genes demonstrated that the 2 genes are adjacent,
      the human UCP2 gene being located 7 kb downstream of the UCP3 gene.

PMID- 10082653
TI  - Light-dependent and rhythmic psbA transcripts in homologous/heterologous
      cyanobacterial cells.
AB  - The psbA2 gene exhibits light-dependent and rhythmic expression in a unicellular
      cyanobacterium, Microcystis aeruginosa (Synechocystis) K-81. To further
      understand the psbA2 expression, biological analyses were performed in homologous
      and heterologous cyanobacterial cells. The results of the experiments using the K
      81 cells revealed that (i) the light-dependent expression appeared on
      transcriptional and/or post-transcriptional level(s) under light/dark cycles,
      (ii) circadian-rhythmic transcripts were also observed under the control of an
      endogenous clock. To assess whether light-dependent and rhythmic psbA2 expression
      occurs in heterologous cyanobacterium, Synechococcus sp. strain PCC 7942, the K
      81 psbA2 5'-upstream region of which the promoter and its around sequences share
      with those of PCC 7942 psbAII, was fused to the bacterial lacZ reporter gene,
      introduced into the genome of PCC 7942 and the psbA2 transcripts were directly
      investigated by primer extension. The K-81 psbA2 specific transcripts were also
      light-dependent and rhythmic in PCC 7942, strongly demonstrating that a common
      regulatory mechanism exists per se for the psbA2 expression in both strains.
      Furthermore, psbA2 expression in the recombinant PCC 7942 strain, AG400 in which
      the region from -404 to +111 of psbA2 is fused to lacZ, exhibited clear
      rhythmicity, while very little or no rhythmicity was observed in AG429 (-38 to
      +14, the only promoter region), suggesting that the region(s) around the promoter
      was essentially required for clear rhythmic expression.

PMID- 10082654
TI  - In vitro binding study of adaptor protein complex (AP-1) to lysosomal targeting
      motif (LI-motif).
AB  - Lysosomal membrane glycoproteins carry targeting information in cytoplasmic
      regions. Two distinct targeting motifs in these regions, GY (glycine-tyrosine)
      and LI (leucine-isoleucine), have been identified and characterized. Accumulating
      evidence suggests that the adaptor complexes (AP-1, AP-2, and AP-3) recognize
      this information in cytoplasmic tails of transmembrane proteins. Here we report
      two different in vitro analyses (affinity beads and surface plasmon resonance)
      which revealed specific interaction between the cytoplasmic tail of LGP85 and AP
      1 but not so with AP-2. We also noted requirement of the LI motif of the LGP85
      tail in binding to the AP-1 complex. Our data and others which indicated the
      binding of AP-3 to the LIMP II (synonym of LGP85) tail suggest that the
      cytoplasmic tail of LGP85 interacts with AP-1 at the trans-Golgi network (TGN)
      and AP-3 at late endosomes, respectively. We propose that this sequential
      interaction between the lysosomal targeting signal and distinct APs along its
      transport pathway is responsible for the critical sorting of lysosomal membrane
      proteins and/or the potential proofreading system of mistargeted molecules.

PMID- 10082655
TI  - Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-related
      gene.
AB  - The tumor suppressor gene MEN1 and several oncogenes including CCND1/cyclin
      D1/PRAD1 map to chromosome 11q13. However, molecular and cytogenetic analysis
      suggests the presence of a second tumor suppressor locus at this chromosome
      region. We have identified a novel gene from chromosome 11q13, which encodes a
      protein of 126 amino acids sharing an overall 57% identity with the p12(DOC-1)
      protein encoded by the DOC-1 gene, the human homolog of hamster putative tumor
      suppressor doc-1 (deleted in oral cancer-1). We therefore designated the novel
      gene as DOC-1R for DOC-1-related. The cytogenetic location was confirmed by
      chromosome fluorescent in situ hybridization. Northern blot analysis indicated
      that it was expressed in all the tissues examined. DOC-1R protein showed
      heterogeneous subcellular localization. RT-PCR-SSCP analysis failed to detect
      deleterious mutations of the DOC-1R transcript in four premalignant oral
      keratinocyte lines and 20 different cancer cell lines from tumor types which
      frequently harbor LOH at chromosome 11q13.

PMID- 10082656
TI  - Retinoic acid potentiates TNF-alpha-induced ICAM-1 expression in normal human
      epidermal keratinocytes.
AB  - ICAM-1 protein in keratinocytes is thought to contribute to cutaneous
      inflammatory reactions. Its induction depends-among others-on cytokines such as
      TNF-alpha, IFN-gamma, IL-1 or on retinoic acid (RA), a key regulator of epidermal
      homeostasis. We investigated the effect of treatments with TNF-alpha, RA or their
      combination on ICAM-1 expression on proliferative or differentiating
      keratinocytes over an 8 day culture period. Basal ICAM-1 levels were undetectable
      at low (30 microM) and standard (88 microM) Ca2+ and RA alone did not induce ICAM
      1. However, at high Ca2+ (1500 microM), ICAM-1 levels were augmented in response
      to RA-treatment. TNF-alpha induced a transient ICAM-1 increase in NHK, which
      reached peak-levels 2-4 days post cytokine stimulus. RA potentiated the TNF-alpha
      induced ICAM-1 response in all Ca2+-concentrations. This potentiating effect of
      RA was confirmed at the mRNA level. In summary, our results establish retinoic
      acid as an enhancer of TNF-alpha-induced ICAM-1 levels in NHK.

PMID- 10082657
TI  - Styrene and styrene oxide affect the transport of dopamine in purified rat
      striatal synaptic vesicles.
AB  - Animal and human studies suggest a dopamine-mediated effect of styrene
      neurotoxicity. To date, mechanisms of cerebral membrane transport of
      neurotransmitter amines in the presence of styrene in relation to its
      neurotoxicity have not been addressed properly. So, the present study has
      examined to test the hypothesis that dopaminergic malfunction in vesicular
      transport is a critical component in styrene-induced neurotoxicity in rats. Both
      styrene and its intermediate reactive metabolite, styrene oxide antagonized the
      in vitro striatal binding of [3H] tyramine, a putative marker of the vesicular
      transporter for dopamine. Both styrene and styrene oxide potently inhibited the
      uptake of [3H] dopamine in purified synaptic vesicles prepared from rat brain
      striata, in a dose-related manner, with inhibitory constants (Ki) 2.5 and 2.2
      microM respectively. However, neither styrene nor styrene oxide significantly
      increased the basal efflux of [3H] dopamine that has been preloaded into striatal
      vesicles in vitro. On the other hand, both styrene and styrene oxide have failed
      to significantly inhibit the uptake of either [3H] norepinephrine, or [3H]
      serotonin into striatal synaptic vesicles. It is concluded that both styrene and
      styrene oxide are capable of producing impairments in dopaminergic transport in
      purified striatal synaptic vesicles, an effect which may be a critical component
      in styrene-induced neurotoxicity.

PMID- 10082658
TI  - Bioconjugation of laminin peptide YIGSR with poly(styrene co-maleic acid)
      increases its antimetastatic effect on lung metastasis of B16-BL6 melanoma cells.
AB  - A comb-shaped polymeric modifier, SMA [poly(styrene comaleic anhydride)], which
      binds to plasma albumin in blood was used to modify the synthetic cell-adhesive
      laminin peptide YIGSR, and its inhibitory effect on experimental lung metastasis
      of B16-BL6 melanoma cells was examined. YIGSR was chemically conjugated with SMA
      via formation of an amide bond between the N-terminal amino group of YIGSR and
      the carboxyl anhydride of SMA. The antimetastatic effect of SMA-conjugated YIGSR
      was approximately 50-fold greater than that of native YIGSR. When injected
      intravenously, SMA-YIGSR showed a 10-fold longer plasma half-life than native
      YIGSR in vivo. In addition, SMA-YIGSR had the same binding affinity to plasma
      albumin as SMA, while native YIGSR did not bind to albumin. These findings
      suggested that the enhanced antimetastatic effect of SMA-YIGSR may be due to its
      prolonged plasma half-life by binding to plasma albumin, and that bioconjugation
      of in vivo unstable peptides with SMA may facilitate their therapeutic use.

PMID- 10082659
TI  - Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis.
AB  - Heparin has a potent angiogenic effect in experimental animals and patients with
      ischemic diseases; however, the precise mechanism behind this angiogenesis
      remains to be clarified. The aim of this study was to determine whether the
      administration of heparin affects the levels of heparin-binding angiogenic
      factors in human plasma, and to identify the molecule responsible for heparin
      induced angiogenesis. Plasma levels of hepatocyte growth factor (HGF), basic
      fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF)
      were measured before and after administration of 100 U, 3,000 U or 10,000 U of
      heparin in patients with coronary artery disease. Administration of 3,000 U or
      10,000 U of heparin caused significant increases in plasma HGF (40- and 54-fold,
      respectively), in absence of obvious increases in bFGF and VEGF levels.
      Furthermore, compared with the serum collected before heparin administration, the
      serum collected after heparin administration had more prominent growth-promoting
      and vascular tube-inducing properties on endothelial cells, and these increased
      activities were completely inhibited by neutralization of HGF, whereas
      neutralization of bFGF and VEGF had no effect. These findings suggest that HGF
      plays a significant role in heparin-induced angiogenesis.

PMID- 10082660
TI  - Generation of highly site-specific DNA double-strand breaks in human cells by the
      homing endonucleases I-PpoI and I-CreI.
AB  - We have determined the ability of two well-characterized eukaryotic homing
      endonucleases, I-PpoI from the myxomycete Physarum polycephalum and I-CreI from
      the green alga Chlamydomonas reinhardtii, to generate site-specific DNA double
      strand breaks in human cells. These 18-kDa proteins cleave highly conserved 15-
      or 24-bp rDNA homing sites in their respective hosts to generate homogeneous 4
      base, 3' ends that initiate target intron transposition or "homing." We show that
      both endonucleases can be expressed in human cells and can generate site-specific
      DNA double-strand breaks in 28S rDNA and homing site plasmids. These endonuclease
      induced breaks can be repaired in vivo, although break repair is mutagenic with
      the frequent generation of short deletions or insertions. I-PpoI and I-CreI
      should be useful for analyzing DNA double-strand break repair in human cells and
      rDNA.

PMID- 10082661
TI  - Regulation of ProMMP-1 and ProMMP-3 activation by tissue factor pathway inhibitor
      2/matrix-associated serine protease inhibitor.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2)/matrix-associated serine protease
      inhibitor (MSPI), a 32- to 33-kDa Kunitz-type serine protease inhibitor, inhibits
      plasmin and trypsin. Because plasmin and trypsin are involved in the activation
      of promatrix metalloproteases proMMP-1 and proMMP-3, we investigated the role of
      TFPI-2/MSPI in the activation of these proenzymes. Both plasmin and trypsin
      activated proMMP-1 by converting the 53-kDa proenzyme to the partially active 43
      kDa polypeptide; this activity was inhibited by TFPI-2/MSPI. Similarly, TFPI
      2/MSPI inhibited the conversion of 66-kDa proMMP-3 to the activated 45- and 30
      kDa polypeptides by plasmin and trypsin. Because plasmin is involved in the
      physiological activation of proMMP-3, we tested whether TFPI-2/MSPI inhibits the
      activation of proMMP-3 by HT-1080 fibrosarcoma cells and urokinase-charged HeLa
      cells. We found that the inhibitor inhibited proMMP-3 activation by HT-1080 cells
      and urokinase-charged HeLa cells. Collectively, our results suggest that TFPI
      2/MSPI indirectly regulates MMP-1- and MMP-3-catalyzed matrix proteolysis by
      regulating the activation of proMMP-1 and proMMP-3.

PMID- 10082662
TI  - Mutations in the p53 and scid genes do not cooperate in lymphomagenesis in doubly
      heterozygous mice.
AB  - Analysis of double mutant mice of the p53 and scid genes, which have a
      combination of cell cycle checkpoint/apoptosis and DNA repair defects, shows that
      the latter defect synergistically enhances lymphoma development with loss of the
      former function. These mice lack the ability to eliminate lymphocytes predisposed
      to neoplastic transformation resulting from faulty antigen receptor gene
      rearrangement. Here we examine the cooperativity in double heterozygotes of p53
      and scid in which normal development of lymphocytes is not impaired. MSM mice
      carrying a p53-knockout allele were crossed with BALB/c mice heterozygous for the
      scid locus and 129 offspring were obtained. They were subjected to gamma-ray
      irradiation, 84 thymic lymphomas being generated. The tumors and host mice were
      genotyped of p53 and scid. Among 42 mice developing p53-deficient lymphomas,
      scid/+ and +/+ genotypes did not provide difference in onset and latency.
      Besides, allelic loss of the Scid gene occurred at a high frequency in those
      lymphomas but the loss exhibited no allelic bias. The results suggest that the
      scid/+ genotype is not a modifier of loss of p53 function in the double
      heterozygotes.

PMID- 10082663
TI  - Selection of a peptide ligand to the p75 neurotrophin receptor death domain and
      determination of its binding sites by NMR.
AB  - The p75 neurotrophin receptor (p75(NTR)) contains a conserved death domain module
      similar to that of the cytotoxic receptors Fas and TNFR-1. Here, we describe the
      selection of peptide ligands from a combinatorial library using a variation of
      the selectively-infective phage (SIP) method directed to the death domain of
      p75(NTR). The binding sites on the death domain of p75(NTR) were identified for a
      15 amino acid residue peptide by nuclear magnetic resonance (NMR) spectroscopy.
      The selected peptides may be useful for probing the function of the p75(NTR)
      death domain and aid in defining its downstream signalling mechanism.

PMID- 10082664
TI  - Transforming growth factor beta triggers two independent-senescence programs in
      cancer cells.
AB  - Transforming growth factor-beta (TGF-beta)TG has been shown to play a
      multifunctional role in tumorigenesis. Here we demonstrate that TGF-beta induces
      a morphological change and expression of senescence-associated beta-galactosidase
      activity in the human lung adenocarcinoma cell line A549 cells within a week
      after the addition. These TGF-beta induced phenotypic changes are thought to
      characterize the rapid onset of senescence. When A549 cells were treated with TGF
      beta, cell growth was not completely arrested, but the activity of telomerase was
      down regulated via transcriptional repression of telomerase reverse
      transcriptase, which led to a shortening of the telomere during long-term culture
      and finally resulted in replicative senescence. These results indicate that TGF
      beta is able to induce a rapid senescence in A549 cells without significantly
      inhibiting cell growth and can further direct A549 cells to a replicative
      senescence state via the suppression of telomerase which culminates in telomere
      shortening. All these experimental results suggest that TGF-beta transmits
      several separate and independent signals to shift A549 cells back to a normal
      senescent cell.

PMID- 10082665
TI  - SHC1, a high pH inducible gene required for growth at alkaline pH in
      Saccharomyces cerevisiae.
AB  - In this study, we carried out a large-scale transposon tagging screening to
      identify genes whose expression is regulated by ambient pH. Of 35,000
      transformants, two strains carrying the genes whose expression is strictly
      dependent on pH of growth medium were identified. One of the genes with 20-fold
      induction by alkali pH was identified as SHC1 gene in the Yeast Genome Directory
      and its expression was the highest at alkaline pH and moderately induced by
      osmotic stress. However, the gene was expressed neither at acidic pH nor by other
      stress conditions. The haploid mutant with truncated shc1 gene showed growth
      retardation and an abnormal morphology at alkaline pH. On the other hand, the
      mutant strain carrying the wild-type SHC1 gene reverted to the mutant phenotype.
      To confirm that Shc1p is an alkali-inducible protein, a monoclonal antibody to
      Shc1p was produced. While a 55-kDa protein band appeared on the Western blot of
      cells grown at alkaline pH, Shc1p was barely detectable on the blots of cells
      grown in YPD. Our results indicate that yeast cells have an efficient system
      adapting to large variations in ambient pH and SHC1 is one of the genes required
      for the growth at alkaline pH.

PMID- 10082666
TI  - Cloning and expression of two carbonyl reductase-like 20beta-hydroxysteroid
      dehydrogenase cDNAs in ovarian follicles of rainbow trout (Oncorhynchus mykiss).
AB  - In salmonid fish, 20beta-hydroxysteroid dehydrogenase (20beta-HSD) is a key
      enzyme involved in the production of oocyte maturation-inducing hormone (MIH),
      17alpha, 20beta-dihydroxy-4-pregnen-3-one. Here we report the isolation of two
      cDNAs which encode proteins with high homology to carbonyl reductase-like 20beta
      HSD (CR/20beta-HSD) from rainbow trout (Oncorhynchus mykiss) ovarian follicles.
      Genomic DNA analysis showed that the two CR/20beta-HSD cDNAs are derived from two
      different genes. Northern blot and RT PCR analysis demonstrated that trout
      CR/20beta-HSDs are broadly expressed in various tissues. Enzymatic
      characterization using recombinant CR/20beta-HSD proteins produced in E. coli
      showed that the product of one of the two cDNAs had both 20beta-HSD and CR
      activity, but the other had neither activity. Although the functional
      significance of the two genes remains unresolved, these results clearly
      demonstrate the presence of two distinct CR/20beta-HSD transcripts in the trout
      ovary.

PMID- 10082667
TI  - IL-1 rescues scleroderma myofibroblasts from serum-starvation-induced cell death.
AB  - Normal senescent adult human fibroblasts are relatively insensitive to the
      effects of serum deprivation in culture. In contrast, the myofibroblast
      phenotype, which is predominant in scleroderma-affected skin and cultured
      fibroblasts from scleroderma-affected skin, shows signs of deterioration within 3
      days of serum starvation. The addition of IL-1 (5 ng/ml) prevents this
      deterioration. We propose that IL-1 is a factor promoting myofibroblast longevity
      with consequent fibrosis in scleroderma skin.

PMID- 10082668
TI  - The NAD+ precursors, nicotinic acid and nicotinamide upregulate glyceraldehyde-3
      phosphate dehydrogenase and glucose-6-phosphate dehydrogenase mRNA in Jurkat
      cells.
AB  - To better understand the role of nicotinic acid and nicotinamide in the
      regulation of the oxidative stress response, we measured the levels of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate
      dehydrogenase (G6PD) mRNA in Jurkat cells treated with these NAD+ precursors. We
      used a modified nonradioactive Northern blot method and detected the mRNA using
      18-mer digoxigenin (DIG)-labeled oligonucleotides as probes. We observed
      increased levels of the mRNAs for the two enzymes in treated cells. Our findings
      suggest that the NAD+ precursors may protect against oxidative stress and DNA
      damage by up-regulating the stress response genes GAPDH and G6PD.

PMID- 10082669
TI  - Isolation of cDNA, chromosome mapping, and expression of the human TBP-like
      protein.
AB  - TBP is an essential factor for eukaryotic transcription. In this study, we
      identified a human cDNA encoding 21-kDa TBP-like protein (TLP). The TLP ORF,
      carrying 186 amino acids, covered the entire 180 amino acids of the C-terminal
      conserved domain of human TBP with 39% identity and 76% similarity. FISH
      determined that human tlp gene was located at chromosome 6 region q22.1-22.3.
      Northern blot analysis demonstrated that TLP mRNAs were expressed in various
      human tissues ubiquitously. We found that the TLP proteins exist in multiple
      mammalian cells and chicken cells. Although the Drosophila TBP-related factor
      (TRF) is a neurogenesis-related transcription factor, expression of TLP was
      nearly constant throughout the neural differentiation of P19 cells. Unlike TRF,
      TLP did not bind to the TATA-box nor direct transcription initiation in vitro.
      Similarity between TRF and TLP was considerably lower (35 in alignment score)
      than that between Drosophila TBP and human TBP (88 in alignment score). Multiple
      amino acids critical for the TBP function were deleted or substituted in TLP. We
      suggest that TLP is not a bona fide vertebrate counterpart nor a direct
      descendant of TRF.

PMID- 10082670
TI  - Kupffer cell-mediated down regulation of rat hepatic CMOAT/MRP2 gene expression.
AB  - Lipopolysaccharides (LPS) induces intrahepatic cholestasis and canalicular
      multispecific organic anion transporter (CMOAT/MRP2) plays a central role in
      hepatic bilirubin transport. This study examined the role of Kupffer cell in LPS
      induced cholestasis. Rats were injected intravenously with LPS. Kupffer cells
      were inactivated with gadolinium chloride (Gd). CMOAT/MRP2 mRNA expression was
      time- and dose-dependently decreased by LPS injection with a decrease in bile
      flow and an increase in serum bilirubin level. Gd pretreatment inhibited decrease
      in CMOAT/MRP2 mRNA and bile flow, and increase in serum bilirubin. Kupffer cell
      conditioned medium decreased CMOAT/MRP2 expression. Addition of anti-IL-1 or anti
      TNFalpha antibody restored CMOAT/MRP2 expression, whereas IL-1 and TNFalpha
      decreased the expression. MAP kinases were activated by addition of the
      conditioned medium, and addition of PD98059 or SB203580 restored CMOAT/MRP2
      expression. These results suggest that LPS activates Kupffer cells to secrete IL
      1 and TNFalpha, which in turn activate MAP kinases and decrease CMOAT/MRP2
      expression.

PMID- 10082671
TI  - A model phosphatase 2C --> phosphatase 1 activation cascade via dual control of
      inhibitor-1 (INH-1) and DARPP-32 dephosphorylation by two inositol glycan
      putative insulin mediators from beef liver.
AB  - Two inositol phosphoglycans (IPG) isolated from beef liver and designated as
      putative insulin mediators were demonstrated to reciprocally enhance the
      dephosphorylation of inhibitor-1 (INH-1) and DARPP-32, thus directly activating
      phosphatase 2C and disinhibiting phosphatase 1 in a potential protein phosphatase
      2C --> phosphatase 1 cascade mechanism. One IPG termed pH 2.0, containing Dchiro
      inositol and galactosamine, stimulated the dephosphorylation of INH-1 and DARPP
      32 in a dose-dependent manner in the low micromolar range. A second, termed pH
      1.3, containing myo-inositol glucosamine and mannose acted reciprocally to
      inhibit the cAMP-dependent protein kinase phosphorylation of INH-1 and DARPP-32
      in a dose-dependent manner in the low micromolar range. These model experiments
      are discussed in terms of the observed dephosphorylation of INH-1 with insulin
      action documented in the literature and the activation of both phosphatase 1 and
      2C described in intact cells and in vivo with insulin action.

PMID- 10082672
TI  - Transcription initiation mediated by initiator binding protein in Saccharomyces
      cerevisiae.
AB  - Many instances of the initiator element in the core promoter of protein-coding
      genes have been reported in mammalian cells and their viruses, but only one has
      been reported in the yeast Saccharomyces cerevisiae at the GAL80 gene. The
      initiator element of GAL80 directs transcription by itself and interacts with a
      nuclear protein designated yeast initiator binding factor (yIF). Here we show
      that yIF in a partially purified sample binds the sequence from -18 to +10 of
      GAL80. By employing a selected and amplified binding procedure, we have
      determined the preferred sequence for yIF binding to be -2 CACTN +3 (N indicates
      any nucleotide). Binding affinity of selected sequences to yIF correlated with
      their initiator-directed transcription in vivo, suggesting that the yIF-initiator
      interaction mediates transcription from the initiator in yeast. We also suggest
      that sequences flanking the preferred sequence affect both yIF binding and
      initiator activity.

PMID- 10082673
TI  - The key amino acid residue of prostaglandin EP3 receptor for governing G protein
      association and activation steps.
AB  - To assess the role of the conserved DPWXY motif of the seventh transmembrane
      domain in prostanoid receptor-mediated G protein activation, we have mutated the
      negatively charged Asp-318 in this motif of the Gi-coupled mouse prostaglandin
      EP3 receptor to uncharged but polar Asn (EP3-D318N) and to the non-polar Leu (EP3
      D318L). The EP3 agonist and antagonist showed similar binding affinities for the
      wild-type and two mutant receptors. The wild-type and EP3-D318N receptors but not
      EP3-D318L receptor associated with Gi in guanine nucleotide- and pertussis toxin
      sensitive manners. On the other hand, the wild-type receptor but not two mutant
      receptors had the ability to stimulate GTPase activity and to inhibit the
      adenylate cyclase. These findings demonstrate that the chemical nature of the
      amino acid residue at position 318 of the seventh transmembrane domain of the EP3
      receptor dissociates the step of Gi association from that of subsequent Gi
      activation in the process of the EP3 receptor-Gi coupling.

PMID- 10082674
TI  - Identification of myosin II as a binding protein to the PH domain of protein
      kinase B.
AB  - Myosin II was identified as a binding protein to the pleckstrin homology (PH)
      domain of protein kinase B (PKB) in CHO cell extract by using the glutathione S
      transferase-fusion protein as a probe. When myosin II purified from rabbit
      skeletal muscle was employed, myosin II was shown to bind almost exclusively to
      the PH domain of PKB among the PH domain fusion proteins examined. The purified
      myosin II bound to the PH domain of PKB with a Kd value of 1.1 x 10(-7) M.
      Studies with a series of truncated molecules indicated that the whole structure
      of the PH domain is required for the binding of myosin II, and the binding to the
      PH domain was inhibited by phosphatidylinositol 4,5-bisphosphate. These results
      suggest that myosin II is a specific binding protein to the PH domain of
      particular proteins including PKB.

PMID- 10082675
TI  - Molecular cloning of CLC chloride channels in Oreochromis mossambicus and their
      functional complementation of yeast CLC gene mutant.
AB  - We have cloned two members of the CLC chloride channel family (OmCLC-3 and OmCLC
      5) from gill cDNA libraries of the euryhaline tilapia Oreochromis mosammbicus. At
      the amino acid level, OmCLC-3 is 90.5% identical to rat CLC-3 and OmCLC-5 is
      79.2% identical to rat CLC-5. Ribonuclease protection assay revealed that OmCLC-5
      was mainly expressed in the gill, kidney, and intestine in both freshwater- (FW)
      and seawater- (SW) adapted tilapia. Although the mRNA of OmCLC-3 was broadly
      expressed in tissues of FW- and SW-adapted tilapia, the most intense signals were
      observed in the gill, kidney, intestine, and brain. Injection of OmCLC-3 and
      OmCLC-5 cRNAs into Xenopus oocytes did not elicit chloride currents, but these
      clones did functionally complement the gef1 phenotype of YPH250(gef), a yeast
      strain in which a single CLC channel (GEF1) has been disrupted by homologous
      recombination. These results clearly indicated that CLC channels closely related
      to the mammalian CLC-3, -4, and -5 subfamily exist also in tilapia and that OmCLC
      3 and OmCLC-5 function as intracellular chloride channels.

PMID- 10082676
TI  - Molecular cloning and expression of a second glucuronyltransferase involved in
      the biosynthesis of the HNK-1 carbohydrate epitope.
AB  - A cDNA encoding a novel glucuronyltransferase was cloned from a rat brain cDNA
      library. The cDNA sequence contained an open reading frame encoding 324 amino
      acids, with type II transmembrane topology. The amino acid sequence revealed 49%
      homology to rat GlcAT-P, a glucuronyltransferase involved in the biosynthesis of
      the HNK-1 carbohydrate epitope of glycoproteins, [Terayama et al. (1997) Proc.
      Natl. Acad. Sci. USA 94, 6093-6098] and the highest sequence homology was found
      in the catalytic region. Northern blot analysis indicated that this newly cloned
      glucuronyltransferase is expressed in the nervous system, consistent with the
      selective localization of the HNK-1 carbohydrate epitope in the nervous system.
      Transfection of this cDNA into COS-1 cells induced the expression of the HNK-1
      carbohydrate epitope on cell surfaces, and induced the morphological changes in
      these cells. These results indicated that this newly cloned cDNA is a second
      glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate
      epitope.

PMID- 10082677
TI  - Reforming British primary care (again)

PMID- 10082678
TI  - Independence days.

PMID- 10082679
TI  - Community development, user involvement, and primary health care.

PMID- 10082680
TI  - Bone marrow transplantation for autoimmune diseases.

PMID- 10082682
TI  - Women with heart disease cautioned about HRT 

PMID- 10082681
TI  - Aspirin for preventing and treating pre-eclampsia.

PMID- 10082684
TI  - In brief 

PMID- 10082683
TI  - Doctors take kidney from patient incapable of giving consent.

PMID- 10082685
TI  - NIH's plans for online publishing could threaten journals.

PMID- 10082686
TI  - Bristol inquiry opens.

PMID- 10082687
TI  - US passes bill protecting low income nursing home patients.

PMID- 10082689
TI  - Colleges issue guidelines to reduce deaths of babies.

PMID- 10082688
TI  - US reports increase in liver cancer 

PMID- 10082690
TI  - Congo polio immunisation campaign gets go ahead.

PMID- 10082691
TI  - Link between pollution and asthma uncovered 

PMID- 10082692
TI  - Walk-in health care.

PMID- 10082694
TI  - Brazil challenges doctors accused of torture.

PMID- 10082695
TI  - South African public sceptical about new AIDS "cure".

PMID- 10082696
TI  - Quality street.

PMID- 10082697
TI  - Risk of primary intracerebral haemorrhage associated with aspirin and non
      steroidal anti-inflammatory drugs: case-control study.
AB  - OBJECTIVE: To examine the association between use of aspirin or other non
      steroidal anti-inflammatory drugs and intracerebral haemorrhage. DESIGN: Case
      control study. SETTING: 13 major city hospitals in the Melbourne and metropolitan
      area. SUBJECTS: 331 consecutive cases of stroke verified by computed tomography
      or postmortem examination, and 331 age (+/- 5 years) and sex matched controls who
      were community based neighbours. INTERVENTIONS: Questionnaire administered to all
      subjects either directly or by proxy with the next of kin. Drug use was validated
      by reviewing prescribing records held by the participants' doctors. MAIN OUTCOME
      MEASURES: Previous use of aspirin or other non-steroidal anti-inflammatory drugs.
      RESULTS: Univariate analysis showed no increased risk of intracerebral
      haemorrhage with low dose aspirin use in the preceding 2 weeks. Using multiple
      logistic regression to control for possible confounding factors, the odds ratio
      associated with the use of aspirin was 1.00 (95% confidence interval 0.60 to 1.
      66, P=0.998) and the odds ratio associated with the use of other non-steroidal
      anti-inflammatory drugs was 0.85 (0.45 to 1.61, P=0. 611) compared with
      respective non-users in the preceding fortnight. Moderate to high doses of
      aspirin (>1225 mg/week spread over at least three doses) yielded an odds ratio of
      3.05 (1.02 to 9.14, P=0. 047). There was no evidence of an increased risk among
      subgroups defined by age, sex, blood pressure status, alcohol intake, smoking,
      and the presence or absence of previous cardiovascular disease. CONCLUSIONS: No
      increase in risk of intracerebral haemorrhage was found among aspirin users
      overall or among those who took low doses of the drug or other non-steroidal anti
      inflammatory drugs. These data provide evidence that doses of aspirin usually
      used for prophylaxis against vascular disease produce no substantial increase in
      risk of intracerebral haemorrhage.

PMID- 10082698
TI  - Onset of adolescent eating disorders: population based cohort study over 3 years.
AB  - OBJECTIVE: To study the predictors of new eating disorders in an adolescent
      cohort. DESIGN: Cohort study over 3 years with six waves. SUBJECTS: Students,
      initially aged 14-15 years, from 44 secondary schools in the state of Victoria,
      Australia. OUTCOME MEASURES: Weight (kg), height (cm), dieting (adolescent
      dieting scale), psychiatric morbidity (revised clinical interview schedule), and
      eating disorder (branched eating disorders test). Eating disorder (partial
      syndrome) was defined when a subject met two criteria for either anorexia nervosa
      or bulimia nervosa according to the Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition (DSM-IV). RESULTS: At the start of the study, 3.3%
      (29/888) of female subjects and 0.3% (2/811) of male subjects had partial
      syndromes of eating disorders. The rate of development of new eating disorder per
      1000 person years of observation was 21.8 in female subjects and 6.0 in male
      subjects. Female subjects who dieted at a severe level were 18 times more likely
      to develop an eating disorder than those who did not diet, and female subjects
      who dieted at a moderate level were five times more likely to develop an eating
      disorder than those who did not diet. Psychiatric morbidity predicted the onset
      of eating disorder independently of dieting status so that those subjects in the
      highest morbidity category had an almost sevenfold increased risk of developing
      an eating disorder. After adjustment for earlier dieting and psychiatric
      morbidity, body mass index, extent of exercise, and sex were not predictive of
      new eating disorders. CONCLUSIONS: Dieting is the most important predictor of new
      eating disorders. Differences in the incidence of eating disorders between sexes
      were largely accounted for by the high rates of earlier dieting and psychiatric
      morbidity in the female subjects. In adolescents, controlling weight by exercise
      rather than diet restriction seems to carry less risk of development of eating
      disorders.

PMID- 10082699
TI  - Surveillance of congenital rubella in Great Britain, 1971-96.

PMID- 10082700
TI  - Cohort study of bacterial species causing urinary tract infection and urinary
      tract abnormalities in children.

PMID- 10082702
TI  - The piano as a cause of neuroses 

PMID- 10082701
TI  - Drug points: severe ergotism associated with interaction between ritonavir and
      ergotamine.

PMID- 10082703
TI  - Unified budgets for primary care groups.

PMID- 10082704
TI  - Setting budgets for general practice in the new NHS.

PMID- 10082705
TI  - A model for clinical governance in primary care groups.

PMID- 10082706
TI  - Towards primary care groups: managing the future in Bradford.

PMID- 10082707
TI  - Forth nightly review: hereditary ovarian carcinoma.

PMID- 10082708
TI  - Evidence based case report: chlamydia infection in general practice.

PMID- 10082709
TI  - ABC of labour care: physiology and management of normal labour.

PMID- 10082710
TI  - For and against: should we fight to preserve the independent status of general
      practitioners?

PMID- 10082711
TI  - Deaf wife 

PMID- 10082712
TI  - Controversies in management: should general practitioners perform diagnostic
      tests on patients before prescribing antibiotics?

PMID- 10082713
TI  - A communication headache 

PMID- 10082714
TI  - Performance indicators for primary care groups. Current indicators have been
      chosen for ease of collection rather than scientific validity.

PMID- 10082715
TI  - Antenatal screening. Obtaining selective consent to scanning, rather than
      screening, is possible.

PMID- 10082716
TI  - Icelandic gene database will uphold patients' rights.

PMID- 10082717
TI  - Modernising mental health services. Personality disorders are arbitrary
      medicalisation of human variation.

PMID- 10082718
TI  - Maggots are useful in treating infected or necrotic wounds.

PMID- 10082719
TI  - Prescribing of nutritional supplements is increasing in general practice.

PMID- 10082720
TI  - BMJ introduces a fast track system for papers. Publication cycle.

PMID- 10082721
TI  - Trends in deaths from malignant neoplasia of liver are poor indicator of
      hepatitis C infection.

PMID- 10082722
TI  - More studies are needed before giving magnesium sulphate for pre-eclampsia.

PMID- 10082723
TI  - Breast screening. No need to reconsider breast screening programme on basis of
      results from defective study.

PMID- 10082724
TI  - Postmarketing surveillance study of a non-chlorofluorocarbon inhaler. Such
      studies initiated by manufacturer are designed to promote product.

PMID- 10082725
TI  - Maintenance programmes are denied to addicted prisoners in Victoria.

PMID- 10082726
TI  - Crisis in cremation. Poor form filling makes medical referees essential.

PMID- 10082727
TI  - Publication time for letters. Letters are not published fast enough in the BMJ.

PMID- 10082728
TI  - Kamal Al-samarraie 

PMID- 10082729
TI  - BMA calls for renewed action on debt relief 

PMID- 10082730
TI  - Jackson pollock 

PMID- 10082731
TI  - Management of acute and chronic pain 

PMID- 10082732
TI  - Patch adams 

PMID- 10082734
TI  - Netlines 

PMID- 10082733
TI  - Website of the week 

PMID- 10082736
TI  - A role for advocacy in general medicine 

PMID- 10082735
TI  - Smoking and women: beauty before age? 

PMID- 10082738
TI  - Aspirin use does not contribute to intracerebral haemorrhage 

PMID- 10082739
TI  - Dieting is linked to adolescent eating disorder 

PMID- 10082741
TI  - Activities to foster quality and accountability in primary care need to be
      coordinated 

PMID- 10082740
TI  - Primary care group budgets will require better information systems and
      collaboration 

PMID- 10082742
TI  - Congenital rubella has fallen dramatically since vaccination started 

PMID- 10082743
TI  - Urinary tract abnormalities are most associated with infections other than E coli

PMID- 10082744
TI  - Immunogold signal amplification: Application of the CARD approach to electron
      microscopy.
AB  - Catalyzed reporter deposition (CARD) is a technique that allows amplification of
      routine immunolabeling in light microscopy. This procedure takes advantage of the
      horseradish peroxidase (HRP) from an HRP-avidin complex to catalyze the
      accumulation of reporter-conjugated tyramine (a phenolic compound) onto a surface
      displaying biotinylated antigen-antibody complexes. The large amount of labeled
      tyramine deposited allows the detection of an antigenic site with multiple
      reporter molecules. In this study we modified this amplification protocol to
      combine it with the immunogold technique for the ultrastructural localization of
      antigens in electron microscopy. We constructed various tyramide conjugates that
      permit the combination of this amplification method with a particulate colloidal
      gold marker. The new probes yield results of high specificity and enhanced
      intensity. Assessment of the level of resolution of the labeling has demonstrated
      that, in spite of the amplification, the resolution remains very good. Therefore,
      once associated, the immunogold and the CARD techniques lead to specific, high
      resolution, sensitive and amplified signals that exhibit the advantages of both
      approaches.(J Histochem Cytochem 47:421-429, 1999)

PMID- 10082745
TI  - An optimized method for in situ hybridization with signal amplification that
      allows the detection of rare mRNAs.
AB  - In situ hybridization (ISH) using nonradioactive probes enables mRNAs to be
      detected with improved cell resolution but compromised sensitivity compared to
      ISH with radiolabeled probes. To detect rare mRNAs, we optimized several
      parameters for ISH using digoxygenin (DIG)-labeled probes, and adapted tyramide
      signal amplification (TSA) in combination with alkaline phosphatase (AP)-based
      visualization. This method, which we term TSA-AP, achieves the high sensitivity
      normally associated with radioactive probes but with the cell resolution of
      chromogenic ISH. Unlike published protocols, long RNA probes (up to 2.61 kb)
      readily permeated cryosections and yielded stronger hybridization signals than
      hydrolyzed probes of equivalent complexity. RNase digestion after hybridization
      was unnecessary and led to a substantial loss of signal intensity without
      significantly reducing nonspecific background. Probe concentration was also a key
      parameter for improving signal-to-noise ratio in ISH. Using these optimized
      methods on rat taste tissue, we detected mRNA for mGluR4, a receptor, and
      transducin, a G-protein, both of which are expressed at very low abundance and
      are believed to be involved in chemosensory transduction. Because the effect of
      the tested parameters was similar for ISH on sections of brain and tongue, we
      believe that these methodological improvements for detecting rare mRNAs may be
      broadly applicable to other tissues. (J Histochem Cytochem 47:431-445, 1999)

PMID- 10082746
TI  - Cellular distribution of endothelin-converting enzyme-1 in human tissues.
AB  - Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin
      biosynthesis, catalyzing the final processing step. As shown by the targeted
      disruption of the ECE-1 gene, mature endothelins must be produced at specific
      sites for normal embryonic development. Therefore, it is important to know the
      exact pattern of ECE-1 gene expression. In this study we investigated the
      cellular distribution of ECE-1 in a variety of human tissues by in situ
      hybridization and immunohistochemistry. Widespread expression of the ECE-1 gene
      was noted, with a similar distribution pattern for mRNA and protein in normal
      human tissues, suggesting a major biological role for ECE-1. ECE-1 levels were
      particularly high in the cardiovascular, reproductive, and endocrine systems.
      There was strong and consistent labeling for ECE-1 in the vascular endothelial
      cells of all organs examined and in various nonvascular cells, especially some
      glandular cells. A large amount of ECE-1 protein and mRNA was detected in the
      Leydig cells of the testis and in the granulosa and theca cells of the ovary. In
      the adrenal gland, ECE-1 was detected in the cortex and medulla, with the
      strongest labeling in the zona glomerulosa. Therefore, ECE-1 may be involved in
      other systems, such as the regulation of hormone secretion, rather than
      exclusively generating ET-1 from its precursor. These results point out the
      potential side effects of ECE-1 inhibitors that are currently under development
      for treatment of cardiovascular diseases. (J Histochem Cytochem 47:447-461, 1999)

PMID- 10082747
TI  - Calcium-induced modification of protein conformation demonstrated by
      immunohistochemistry: What is the signal?
AB  - A recent study by Morgan et al. on the mechanism of the heating antigen retrieval
      (AR) has raised an interesting issue concerning calcium-induced modification of
      protein conformation demonstrated by immunohistochemistry (IHC). The current
      study is based on calcium-induced modification of thrombospondin (TSP) and Ki-67,
      as demonstrated by IHC using seven monoclonal antibodies (MAbs) to TSP and an MAb
      MIB1. Experiments were carried out on frozen tissue sections of bladder carcinoma
      and lymph node. Frozen sections were incubated with solutions of 50 mM CaCl2
      and/or 10 mM EDTA at 4C overnight before formalin or acetone fixation for TSP and
      Ki-67, respectively. Sections were then fixed in 10% neutral buffered formalin or
      acetone before immunostaining. Seven MAbs to TSP, named Ab1 to 7 representing
      clone numbers of A4.1, D4.6, C6.7, A6.1, B5.2, A2.5, and HB8432, respectively,
      and MIB1 were utilized as primary antibodies. ABC was used as the detection
      system and AEC as the chromogen for immunohistochemical staining. An
      extracellular immunostaining pattern represented a positive result for TSP, and
      nuclear staining for MIB1. Frozen sections preincubated in 50 mM CaCl2 overnight
      at 4C showed significant loss of staining and/or altered staining pattern for six
      of the seven antibodies to TSP and MIB1 compared to positive controls not exposed
      to CaCl2. Lack of immunostaining of TSP and MIB1 attributable to exposure to
      CaCl2 could be partially recovered by incubating the frozen sections in EDTA.
      Calcium-induced modification of protein structure was demonstrated more than 10
      years ago on the basis of immunochemical techniques. In this study, similar
      calcium-induced modification of protein was detectable by IHC in frozen tissue
      sections, suggesting that calcium-induced modification of protein structure may
      occur independently of fixation-induced modification. The fact that calcium
      binding may affect IHC staining is not surprising in view of the fact that
      antibody/antigen interactions are protein structure-dependent. However, in this
      experiment the change occurred before and independent of formalin fixation and
      does not necessarily imply a role for calcium in AR. There may be a valuable role
      for the use of chemical modification in visualization of protein structure
      changes in tissue sections by IHC. (J Histochem Cytochem 47:463-469, 1999)

PMID- 10082748
TI  - Bridging the resolution gap: Imaging the same transcription factories in
      cryosections by light and electron microscopy.
AB  - The resolution of conventional light microscopy is limited to approximately 200
      nm in the x- and y-axes and >500 nm in the z-axis. A simple way of improving z
      axis resolution is to analyze thin sections of 100-200 nm. The utility of such an
      approach is illustrated by reference to transcription sites imaged in
      cryosections of human nuclei. Cells are permeabilized, allowed to extend nascent
      transcripts in Br-UTP, fixed, cryosectioned, and Br-RNA-immunolabeled with
      fluorochromes and gold particles. As expected, physical sectioning improves
      resolution and brings other advantages. First, sections allow improved antibody
      access and better immunolabeling. Second, more sites (with a more representative
      range of intensities) can now be resolved against lower backgrounds, facilitating
      quantitative analysis. Third, problems associated with chromatic aberration when
      two differently colored images of the same objects are collected can be
      sidestepped by refocusing between image collection. Fourth, exactly the same
      sites can be imaged by light and electron microscopy, allowing direct comparison
      between the two techniques. Immunogold labeling and electron microscopy provided
      the most accurate counts of site number. The results confirm that nascent
      transcripts in the nucleoplasm are confined to several thousand sites, or
      "factories," with diameters of approximately 40 nm. (J Histochem Cytochem 47:471
      480, 1999)

PMID- 10082749
TI  - Keratan sulfate glycosaminoglycans in murine eosinophil-specific granules.
AB  - We examined the presence of sialyl glycoconjugates in specific granules from
      murine bone marrow eosinophils. Lectin cytochemistry using Maackia amurensis
      lectin II (MAL II) specific for sialyl alpha-2,3 galactose residues demonstrated
      positive labeling in both immature and mature specific granules. Pretreatment
      with Clostridium neuraminidase or keratanase II eliminated the positive labeling
      of MAL II in the specific granules. High iron diamine-thiocarbohydrazide-silver
      proteinate physical development (HID-TCH-SP-PD) staining, which is specific for
      sulfated glycoconjugates, also positively labeled immature specific granules
      lacking crystalloids but not mature granules with crystalloids. Pretreatment with
      a combination of chondroitinase ABC and keratanase, or a combination of
      chondroitinase ABC and keratanase II, eliminated the positive labeling obtained
      with HID-TCH-SP-PD. These results indicate that the sialyl residues detected by
      MAL II are expressed as terminal sugar residues of keratan sulfate proteoglycan,
      which appears to be of the corneal type in view of its sensitivity to keratanase
      and keratanase II. (J Histochem Cytochem 47:481-488, 1999)

PMID- 10082750
TI  - Specific localization of membrane dipeptidase and dipeptidyl peptidase IV in
      secretion granules of two different pancreatic islet cells.
AB  - Endocrine cells require several protein convertases to process the precursors of
      hormonal peptides that they secrete. In addition to the convertases, which have a
      crucial role in the maturation of prohormones, many other proteases are present
      in endocrine cells, the roles of which are less well established. Two of these
      proteases, dipeptidyl peptidase IV (EC 3.4.14.5) and membrane dipeptidase (EC
      3.4.13.19), have been immunocytochemically localized in the endocrine pancreas of
      the pig. Membrane dipeptidase was present exclusively in cells of the islet of
      Langerhans that were positive for the pancreatic polypeptide, whereas dipeptidyl
      peptidase IV was restricted to cells positive for glucagon. Both enzymes were
      observed in the content of secretory granules and therefore would be released
      into the interstitial space as the granules undergo exocytosis. At this location
      they could act on secretions of other islet cells. The relative concentration of
      dipeptidyl peptidase IV was lower in dense glucagon granules, where the
      immunoreactivity to glucagon was higher, and vice versa for light granules. This
      suggests that, in A-cells, dipeptidyl peptidase IV could be sent for degradation
      in the endosomal/lysosomal compartment during the process of granule maturation
      or could be removed from granules for continuous release into the interstitial
      space. The intense proteolytic activity that takes place in the endocrine
      pancreas could produce many potential dipeptide substrates for membrane
      dipeptidase. (J Histochem Cytochem 47:489-497, 1999)

PMID- 10082751
TI  - Characterization of integrin expression in islets isolated from hamster, canine,
      porcine, and human pancreas.
AB  - The reasons for the failure of clinical islet transplantation remain obscure.
      Islet isolation, however, exposes the islet to variety of cellular stresses,
      including disruption of the cell-matrix relationship, an event associated with
      apoptosis. The cell-matrix relationship is characterized by an interaction
      between cell surface integrin receptors and matrix molecules of the surrounding
      basement membrane (BM). The purpose of this study was to characterize integrin
      expression and the distribution of the peri-insular BM in human, porcine, canine,
      and hamster pancreas, and after routine islet isolation. Whereas islets in the
      porcine pancreas do not have a demonstrable BM, islets in the human, canine, and
      hamster pancreas have an almost continuous BM with very little direct exocrine to
      endocrine cell-cell contact. After islet isolation, the BM was destroyed, only to
      be reestablished during the period of culture. In the pancreas of all four
      species, integrin alpha3 was expressed only on islet cells, and integrin alpha5
      was present on islet cells as well as on acinar, centroacinar, and duct cells.
      Integrin alphaV was detected only in human and canine pancreas. Integrin beta1
      was demonstrated only in the human pancreas. In isolated islets, integrin alpha3,
      alpha5, and alphaV expression decreased during the culture period and the
      intensity of the staining was observed to be coincident with the distribution of
      the BM. In summary, this is the first report of integrin expression in hamster,
      canine, porcine, and human islets. After islet isolation, the altered islet cell
      matrix relationship is reflected both in the decrease in integrin expression and
      in the destruction of the peri-insular BM. These profound changes will need to be
      considered as the process of islet isolation for transplantation is refined. (J
      Histochem Cytochem 47:499-506, 1999)

PMID- 10082752
TI  - Characterization of a specific antibody to the rat angiotensin II AT1 receptor.
AB  - We raised a polyclonal antibody against a decapeptide corresponding to the
      carboxyl terminus of the rat angiotensin II AT1 receptor. This antibody was
      demonstrated to be specific for the rat receptor according to a number of
      approaches. These included (a) the ultrastructural localization of immunogold
      labeled receptor on the surfaces of zona glomerulosa cells in the adrenal cortex,
      (b) the specific labeling of Chinese hamster ovarian (CHO) cells transfected with
      AT1 receptors, (c) the identification of a specific band on Western blots, (d)
      the immunocytochemical co-localization of angiotensin receptors on neurons in the
      lamina terminalis of the brain shown to be responsive to circulating angiotensin
      II, as shown by the expression of c-fos, and (e) the correlation between the
      expression of the mRNA of the AT1 receptor and AT1 receptor immunoreactivity.(J
      Histochem Cytochem 47:507-515, 1999)

PMID- 10082753
TI  - Cell-specific expression of mitochondrial carbonic anhydrase in the human and rat
      gastrointestinal tract.
AB  - Mitochondrial carbonic anhydrase V (CA V) in liver provides HCO3- to pyruvate
      carboxylase for the first step in gluconeogenesis and HCO3- to carbamyl phosphate
      synthetase I for the first step in ureagenesis. Because carbamyl phosphate
      synthetase I and ornithine transcarbamylase are also expressed in enterocytes, we
      tested the hypothesis that CA V is expressed in the gastrointestinal tract in
      addition to liver. Polyclonal rabbit antisera were raised against a polypeptide
      of 17 C-terminal amino acids of human CA V and against purified recombinant mouse
      isozyme and were used in Western blotting and immunoperoxidase staining of human
      and rat tissues. Immunohistochemistry showed that CA V is expressed cell
      specifically in the alimentary canal mucosa from stomach to rectum.
      Immunoreactions for CA V were detected in the parietal cells and gastrin
      producing G-cells of the stomach and in intestinal enterocytes. Western blotting
      of human and rat gastrointestinal tissues with isozyme-specific antibodies showed
      positive signals for CA V with the expected molecular mass. The findings in human
      tissues paralleled those in rat. The cell-specific pattern of CA V expression
      suggests a role for CA V in alimentary canal physiology. We propose that
      mitochondrial CA V participates in the detoxification of ammonia produced in the
      gastrointestinal tract by providing bicarbonate to carbamyl phosphate synthetase
      I. (J Histochem Cytochem 47:517-524, 1999)

PMID- 10082754
TI  - Ultrastructural localization of S100A3, a cysteine-rich, calcium binding protein,
      in human scalp hair shafts revealed by rapid-freezing immunocytochemistry.
AB  - We have characterized the subcellular distribution of S100A3, a cysteine-rich
      calcium binding protein, in human scalp hair shaft. This was accomplished using
      rapid-freezing immunocytochemistry, a technique that combines rapid-freezing,
      freeze-substitution fixation without chemical fixatives, and subsequent electron
      microscopic detection of immunocytochemical labeling. This technique preserves
      both the antigenicity and the ultrastructural integrity of fully keratinized
      tissues, which are highly unmanageable when prepared for immunoelectron
      microscopy. In the hair shaft, S100A3 was primarily identified in the endocuticle
      and was also present in the intermacrofibrillar matrix surrounding macrofibril
      bundles of intermediate filament keratins in cortex cells. Double immunolabeling
      of S100A3 and hair keratins revealed the in situ spatial relationship between
      them. In the endocuticle, S100A3 was present on the inner portion of the
      endocuticle adjacent to the cell membrane complex, whereas hair keratins were
      present on the outer portion. These results provide the first ultrastructural
      evidence that an S100 protein is localized in specific subcompartments in human
      hair cells. (J Histochem Cytochem 47:525-532, 1999)

PMID- 10082755
TI  - Differential expression of thrombospondin and cellular fibronectin during
      remodeling in proliferative glomerulonephritis.
AB  - Thrombospondin-1 (TSP-1) and an alternatively spliced fibronectin (Fn)-EIIIA
      isoform are adhesive proteins associated with embryogenesis and tissue
      remodeling. We compared, by immunohistochemistry and in situ hybridization, the
      course of TSP-1 and Fn-EIIIA expression in a model of glomerulonephritis induced
      by Habu snake venom (HV) and characterized by mesangial cell migration,
      proliferation, and extracellular matrix (ECM) synthesis. At 24 hr after HV, TSP-1
      and Fn-EIIIA proteins localized in the central aspects of lesions associated with
      platelets and macrophages and at the margins of lesions coinciding with mesangial
      cell migration (determined by Thy-1 staining). Mesangial cells at this time
      expressed TSP-1 but not Fn-EIIIA mRNA. TSP-1 protein and mRNA peaked in lesions
      at 48 hr and were associated with cell proliferation (determined by PCNA, alpha
      smooth muscle actin phenotype, and expression of beta-PDGF receptor mRNA). TSP-1
      expression declined at 72 hr when expression of ECM synthesis peaked, as
      determined by increased expression of collagen Type IV, laminin, and TGF-beta1
      protein and mRNA. Mesangial cell expression of Fn-EIIIA was first observed at 48
      hr and was most abundant at 72 hr after HV. Therefore, platelet- and macrophage
      derived Fn-EIIIA and TSP-1 in early lesions are associated with mesangial cell
      migration. Mesangial cell upregulation of TSP-1 is associated with migration and
      proliferation but not maximal ECM accumulation, whereas mesangial cell expression
      of Fn-EIIIA is associated with proliferation and ECM accumulation. These results
      suggest distinctive temporal and spatial roles for TSP-1 and Fn-EIIIA in
      remodeling during glomerular disease. (J Histochem Cytochem 47:533-543, 1999)

PMID- 10082756
TI  - Localization of carbonic anhydrase in living osteoclasts with bodipy 558/568
      modified acetazolamide, a thiadiazole carbonic anhydrase inhibitor.
AB  - We describe the synthesis of Bodipy 558/568-modified acetazolamide, a fluorescent
      inhibitor of carbonic anhydrase and its use to localize the enzyme in living
      cells. The modified acetazolamide, with its specific sulfonamide group intact,
      labeled cells at concentrations as low as 10(-9) M, with a minimal loading time
      of 5 min. The staining was decreased by 57.4% by preincubating cells with
      unaltered acetazolamide (1:100) or with trifluoromethane sulfonamide, 6
      ethoxyzolamide, and 5-(3-hydroxybenzoyl)-thiophene-2-sulfonamide. The efficacy of
      the inhibitor was unchanged by the fluorescent label, as determined by an
      acridine orange assay that detects acidification of osteoclasts, the cell model
      used in this study. This compound should prove to be useful for studying carbonic
      anhydrase in many organisms because of the high degree of conservation of the
      active site of this enzyme. (J Histochem Cytochem 47:545-550, 1999)

PMID- 10082757
TI  - In situ hybridization and immunohistochemical analysis of the expression of
      cardiotoxin and neurotoxin genes in Naja naja sputatrix.
AB  - Secretory processes and their regulation have been extensively studied in
      mammalian salivary parotid glands. However, little is known regarding the
      secretory mechanism in the venom glands of snakes, which invariably produce one
      of the most complex of all animal secretions. The pharmacologically important and
      toxic components of the Malayan spitting cobra (Naja naja sputatrix) venom
      include postsynaptic neurotoxins (NTX), presynaptic neurotoxins (phospholipase
      A2, PLA2), and cardiotoxins (CTX) which, for convenience, have been collectively
      referred to as "toxins." We report here for the first time the mechanism of toxin
      gene expression by studying the accumulated mRNA level and protein synthesis
      rates for the three toxins over a period of 8 days after stimulation of venom
      synthesis by manual "milking" of the venom gland. Immunofluorescence and in situ
      hybridization were used to localize the toxins and their mRNAs in venom gland
      sections. The rate of protein synthesis, as determined by immunofluorescence and
      liquid chromatography-mass spectrometry (LC-MS) techniques, increased in parallel
      with the increase in the toxin mRNA content in the secretory epithelial cells,
      suggesting that transcriptional regulation of the toxin genes is involved. (J
      Histochem Cytochem 47:551-560, 1999)

PMID- 10082758
TI  - Detection of fragmented DNA in apoptotic cells embedded in LR white: A combined
      histochemical (LM) and ultrastructural (EM) study.
AB  - We developed an improved method for the detection of double-strand DNA breaks in
      apoptotic cells at both the light (LM) and electron microscopic (EM) levels using
      a modification of the TdT (terminal deoxynucleotidyl transferase)-mediated dUTP
      nick end-labeling (TUNEL) technique. Cultured rat cerebellar granule cells were
      exposed to low potassium conditions to induce apoptosis. Twenty-four hr after
      treatment, one group of cells was fixed in situ with 4% paraformaldehyde and
      labeled for DNA fragmentation characteristic of apoptosis. Apoptotic cells were
      visualized with diaminobenzidine (DAB) and viewed by LM. The second group of
      cells was detached from the culture dish, pelleted, fixed with a 4%
      paraformaldehyde and 0. 2% glutaraldehyde mixture, and embedded in LR White. For
      LM, the modified TUNEL technique was performed on 1.5-microm LR White sections
      and apoptotic cells were visualized using an enzymatic reaction to generate a
      blue precipitate. For EM, thin sections (94 nm) were processed and DNA
      fragmentation was identified using modified TUNEL with streptavidin-conjugated
      gold in conjunction with in-depth ultrastructural detail. Alternate sections of
      cells embedded in LR White can therefore be used for LM and EM TUNEL-based
      detection of apoptosis. The present findings suggest that the modified TUNEL
      technique on LR White semithin and consecutive thin sections has useful
      application for studying the fundamental mechanism of cell death. (J Histochem
      Cytochem 47:561-568, 1999)

PMID- 10082759
TI  - High-resolution immunocytochemical labeling of replicas with ultrasmall gold.
AB  - The use of 10-15-nm gold probes in freeze-fracture immunocytochemistry sometimes
      results in poor immunogold labeling. Replica sites are labeled with only one or
      two gold particles, making it unlikely that the labeling depicts the true
      distribution of antigen. In this study, the feasibility of using ultrasmall (
      approximately 1.4-nm) gold probes for immunocytochemical labeling of replicas was
      examined. When HLA Class I in neutrophil membrane replicas was labeled with
      various sized immunogold particles as the secondary detection system, the
      apparent distribution density was inversely related to the size of the particles
      (1.4-nm > 5-nm >10-nm >15-nm). Indeed, the density of the apparent distribution
      of HLA Class I labeled with 1.4-nm gold particles was about sevenfold greater
      than when labeling was carried out with the 10-nm gold particles. Similar results
      were obtained with CD16, another neutrophil membrane protein. Silver enhancement
      was required to visualize the 1.4-nm gold particles, but this procedure did not
      adversely affect replica membranes. These results suggest that, when followed by
      silver enhancement, 1.4-nm gold particles are effective probes for achieving high
      resolution immunocytochemical labeling of replicas.(J Histochem Cytochem 47:569
      573, 1999)

PMID- 10082760
TI  - Harold Henderson Williams (1907-1991).

PMID- 10082761
TI  - Transcriptional regulation of interleukin-2 gene expression is impaired by copper
      deficiency in Jurkat human T lymphocytes.
AB  - Copper deficiency reduces secretion of the cytokine interleukin-2 (IL-2) by
      activated rodent splenocytes, human peripheral blood mononuclear cells and Jurkat
      cells, a human T lymphocyte cell line. Previous studies showed that low Cu status
      also decreased the level of IL-2 mRNA in activated Jurkat cells by 50%. Synthesis
      of this cytokine is regulated by alterations in transcription of the IL-2 gene
      and the stability of IL-2 mRNA. To determine if Cu status influenced promoter
      activity of the IL-2 gene, Jurkat cells were transfected with a luciferase
      reporter gene construct containing the entire 300 bp human IL-2 promoter/enhancer
      sequence. Cu deficiency was induced by incubating stably transfected cells with
      the Cu chelator 2,3,2-tetraamine for 35 h prior to activating cells with
      phytohemagglutinin-P and phorbol myristate acetate. Luciferase activity in
      lysates of Cu-deficient cells was approximately 50% lower in several multiclonal
      and clonal cell lines of stably transfected cells than in replicate cultures that
      were not exposed to chelator. The relative levels of endogenous IL-2 bioactivity
      and luciferase activity were highly correlated in the transfected cell lines. The
      chelator-mediated reduction in reporter gene activity was dose-dependent at
      levels of 5-40 micromol 2,3,2-tetraamine/L. The addition of a slight molar excess
      of Cu, but not Zn or Fe, to medium containing 2,3,2-tetraamine prevented the
      decline in luciferase activity. IL-2 mRNA stability in parental Jurkat cells was
      independent of Cu status. These data indicate that decreased cellular Cu
      attenuates IL-2 synthesis in T lymphocytes by inhibiting transcription of the IL
      2 gene.

PMID- 10082762
TI  - Conjugated linoleic acid inhibits differentiation of pre- and post- confluent 3T3
      L1 preadipocytes but inhibits cell proliferation only in preconfluent cells.
AB  - Conjugated linoleic acid (CLA; 18:2) is a group of isomers (mainly 9-cis, 11
      trans and 10-trans, 12-cis) of linoleic acid. CLA is the product of rumen
      fermentation and can be found in the milk and muscle of ruminants. Animals fed
      CLA have a lower body fat content. The objective of this study was to establish
      the possible mechanisms by which CLA affects adipogenesis. 3T3-L1 is a well
      established cell line that is used extensively in studying adipocyte biology.
      These cells typically grow in a culture medium until they reach confluence, at
      which time they are induced to differentiate by hormonal treatment (d 0).
      Treatment of 3T3-L1 cells with 25 to 100 micromol/L CLA inhibited differentiation
      in a dose-dependent manner, while linoleic acid treatment did not differ from
      DMSO-treated controls. Continuous treatment from d -2, -1, 0 or 2 to d 8 and
      treatment from d -2 to d 0 and from d 0 to d 2 inhibited differentiation.
      Differentiation was monitored morphologically (oil Red-O staining), enzymatically
      (reduction of activity of glycerol-3-phosphate dehydrogenase), and by northern
      analysis of peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer
      binding protein alpha and adipocyte specific protein 2 mRNA. CLA inhibited cell
      proliferation of nonconfluent cells but did not affect cell division of confluent
      cells, as indicated by 5-bromo-2'-deoxyuridine incorporation and mitochondria
      metabolism. Therefore, CLA inhibited differentiation before confluence and during
      induction. However, cellular proliferation was only inhibited prior to induction.
      These results imply that fat reduction caused by CLA treatment may be attributed
      to its inhibition of both proliferation and differentiation of preadipocytes in
      animals.

PMID- 10082763
TI  - Dietary calcium phosphate stimulates intestinal lactobacilli and decreases the
      severity of a salmonella infection in rats.
AB  - We have shown recently that dietary calcium phosphate (CaPi) has a trophic effect
      on the intestinal microflora and strongly protects against salmonella infection.
      It was speculated that precipitation by CaPi of intestinal surfactants, such as
      bile acids and fatty acids, reduced the cytotoxicity of intestinal contents and
      favored growth of the microflora. Because lactobacilli may have antagonistic
      activity against pathogens, the main purpose of the present study was to examine
      whether this CaPi-induced protection coincides with a reinforcement of the
      endogenous lactobacilli. In vitro, Salmonella enteritidis appeared to be
      insensitive to bile acids and fatty acids, whereas Lactobacillus acidophilus was
      killed by physiologically relevant concentrations of these surfactants.
      Additionally, after adaptation to a purified diet differing only in CaPi
      concentration (20 and 180 mmol CaHPO4. 2H2O/kg), rats (n = 8) were orally
      infected with S. enteritidis. Besides reducing the cytotoxicity and the
      concentration of bile acids and fatty acids of ileal contents and fecal water,
      CaPi notably changed the composition of ileal bile acids in a less cell-damaging
      direction. Significantly greater numbers of ileal and fecal lactobacilli were
      detected in noninfected, CaPi-supplemented rats. As judged by the lower urinary
      NOx excretion, which is a biomarker of intestinal bacterial translocation,
      dietary CaPi reduced the invasion of salmonella. Additionally, the colonization
      resistance was improved considering the reduction of excreted fecal salmonella.
      In accordance, fewer viable salmonella were detected in ileal contents and on the
      ileal mucosa in the CaPi group. In conclusion, reducing the intestinal surfactant
      concentration by dietary CaPi strengthens the endogenous lactobacilli and
      increases the resistance to salmonella.

PMID- 10082764
TI  - Weaning anorexia may contribute to local inflammation in the piglet small
      intestine.
AB  - Compromising alterations in villus-crypt structure are common in pigs
      postweaning. Possible contributions of local inflammatory reactions to villus
      crypt alterations during the weaning transition have not been described. This
      study evaluated local inflammatory responses and their relationship with
      morphological changes in the intestine in 21-d-old pigs (n = 112) killed either
      at weaning (Day 0) or 0.5, 1, 2, 4 or 7 d after weaning to either milk- or soy
      based pelleted diets. Cumulative intake averaged <100 g during the first 2 d
      postweaning, regardless of diet. During this period of weaning anorexia,
      inflammatory T-cell numbers and local expression of the matrix metalloproteinase
      stromelysin increased while jejunal villus height, crypt depth and major
      histocompatibility complex (MHC) class I RNA expression decreased. Upon
      resumption of feed intake by the fourth d postweaning, villus height and crypt
      depth, CD8(+) T cell numbers, MHC class I RNA expression and local expression of
      stromelysin returned to Day 0 values. Together the results indicate that
      inadequate feed intake during the immediate postweaning period may contribute to
      intestinal inflammation and thereby compromise villus-crypt structure and
      function.

PMID- 10082765
TI  - Expression of T lymphocyte p56(lck), a zinc-finger signal transduction protein,
      is elevated by dietary zinc deficiency and diet restriction in mice.
AB  - Compromised immune function is common to Zn deficiency, protein and energy
      malnutrition; however, the causative mechanisms at the molecular level have not
      been elucidated. The T lymphocyte signal transduction pathway contains several Zn
      finger proteins, and it is possible that the in vivo functioning of these
      proteins could be affected by dietary deficiency of Zn and amino acids. Thus, the
      objective was to investigate the effects, on expression of the T lymphocyte
      signal transduction proteins p56(lck), phospholipase Cgamma1 (PLCgamma1) and
      protein kinase C (PKCalpha), of dietary Zn deficiency (ZnDF, < 1 mg Zn/kg diet)
      and protein-energy malnutrition syndromes [2% protein deficiency (LP), combined
      Zn and 2% protein deficiency (ZnDF+LP), and diet restriction (DR, body weight
      equal to ZnDF)] compared with control (C) mice. Indices of nutritional status and
      splenocyte counts were also determined. Based on serum albumin and liver lipid
      concentrations, the ZnDF+LP and LP groups had protein-type malnutrition, whereas
      the ZnDF and DR groups had energy-type malnutrition. For Western immunoblotting
      of the signal transduction proteins, mouse splenic T lymphocytes were isolated by
      immunocolumns. The expression of T lymphocyte p56(lck) was significantly elevated
      in the ZnDF+LP, ZnDF and DR groups compared to the C group. In contrast, the
      expression of PLCgamma1 and PKC was unaffected. There was a significant negative
      correlation between T lymphocyte p56(lck) expression and serum Zn (r= -0.65, P =
      0.0007) or femur Zn (r = -0.73, P = 0.0001) concentrations. We propose that
      elevated T lymphocyte p56(lck) may contribute to altered thymoctye maturation,
      apoptosis and lymphopenia in Zn deficiency and protein-energy malnutrition
      syndromes.

PMID- 10082766
TI  - Dietary pectin lowers sphingomyelin concentration in VLDL and raises hepatic
      sphingomyelinase activity in rats.
AB  - There is evidence that cholesterol and sphingomyelin metabolism are interrelated,
      and thus the hypothesis tested was that dietary pectin, because it can alter
      hepatic cholesterol metabolism, would also alter hepatic sphingomyelin
      metabolism. For that purpose, 4-wk-old female Wistar rats were fed a diet without
      or with pectin (20 g/100 g) up to 21 d. In accordance with previous work, pectin
      consumption caused a significant (P < 0.001) reduction in hepatic (65%), whole
      plasma (37%), and VLDL (80%) cholesterol levels. Pectin also significantly
      reduced VLDL sphingomyelin concentrations (57%), but raised the amount of
      sphingomyelin in the high density lipoproteins (HDL)-2 fractions (58%), so that
      the level of sphingomyelin in whole plasma remained unaffected. Pectin did not
      affect the sphingomyelin concentration in the liver. Pectin consumption did not
      affect the hepatic sphingomyelin synthesizing enzymes, serine
      palmitoyltransferase, phosphatidylcholine:ceramide phosphocholine transferase, or
      phosphatidylethanolamine:ceramide phosphoethanolamine transferase. In contrast,
      dietary pectin activated both lysosomal (28%) and plasma membrane (26%)
      sphingomyelinase and thus may have enhanced sphingomyelin degradation. An attempt
      was made to describe the effects of dietary pectin on sphingomyelin metabolism in
      terms of altered fluxes through liver and plasma, with whole liver and whole
      plasma concentrations of sphingomyelin remaining unaffected.

PMID- 10082767
TI  - The isoflavone genistein inhibits internalization of enteric bacteria by cultured
      Caco-2 and HT-29 enterocytes.
AB  - The dietary isoflavone genistein is the focus of much research involving its role
      as a potential therapeutic agent in a variety of diseases, including cancer and
      heart disease. However, there is recent evidence that dietary genistein may also
      have an inhibitory effect on extraintestinal invasion of enteric bacteria. To
      study the effects of genistein on bacterial adherence and internalization by
      confluent enterocytes, Caco-2 and HT-29 enterocytes (cultivated for 15-18 d and
      21-24 d, respectively) were pretreated for 1 h with 0, 30, 100, or 300 micromol/L
      genistein, followed by 1-h incubation with pure cultures of Listeria
      monocytogenes, Salmonella typhimurium, Proteus mirabilis, or Escherichia coli.
      Pretreatment of Caco-2 and HT-29 enterocytes with genistein inhibited bacterial
      internalization in a dose-dependent manner (r = 0.60-0.79). Compared to untreated
      enterocytes, 1-h pretreatment with 300 micromol/L genistein was generally
      associated with decreased bacterial internalization (P < 0. 05) without a
      corresponding decrease in bacterial adherence. Using Caco-2 cell cultures,
      decreased bacterial internalization was associated with increased integrity of
      enterocyte tight junctions [measured by increased transepithelial electrical
      resistance (TEER)], with alterations in the distribution of enterocyte
      perijunctional actin filaments (visualized by fluorescein-labeled phalloidin),
      and with abrogation of the decreased TEER associated with S. typhimurium and E.
      coli incubation with the enterocytes (P < 0.01). Thus, genistein was associated
      with inhibition of enterocyte internalization of enteric bacteria by a mechanism
      that might be related to the integrity of the enterocyte tight junctions,
      suggesting that genistein might function as a barrier-sustaining agent,
      inhibiting extraintestinal invasion of enteric bacteria.

PMID- 10082768
TI  - Dietary thiamin level influences levels of its diphosphate form and thiamin
      dependent enzymic activities of rat liver.
AB  - This study was prompted by our incomplete understanding of the mechanism
      responsible for the clinical benefits of pharmacological doses of thiamin in some
      patients with maple syrup urine disease (MSUD) and the question of whether
      thiamin diphosphate (TDP), a potent inhibitor of the activity of the protein
      kinase that phosphorylates and inactivates the isolated branched-chain alpha
      ketoacid dehydrogenase (BCKDH) complex, affects the activity state of the
      complex. Rats were fed a chemically-defined diet containing graded levels of
      thiamin (0, 0.275, 0.55, 5.5, and 55 mg thiamin/kg diet). Maximal weight gain was
      attained over a 3-wk period only in rats fed diets with 5.5 and 55 mg thiamin/kg.
      Feeding rats the thiamin-free diet for just 2 d caused loss of nearly half of the
      TDP from liver mitochondria. Three more days caused over 70% loss, an additional
      3 wk, over 90%. Starvation for 2 d had no effect, suggesting a mechanism for
      conservation of TDP in this nutritional state. Mitochondrial TDP was higher in
      rats fed pharmacological amounts of thiamin (55 mg thiamin/kg diet) than in rats
      fed adequate thiamin for maximal growth. Varying dietary thiamin had marked but
      opposite effects on the activities of alpha-ketoglutarate dehydrogenase (alpha
      KGDH) and BCKDH. Thiamin deficiency decreased alpha-KGDH activity, increased
      BCKDH activity, and increased the proportion of BCKDH in the active,
      dephosphorylated, state. Excess dietary thiamin had the opposite effects. TDP
      appears to be more tightly associated with alpha-KGDH than BCKDH in thiamin
      deficient rats, perhaps denoting retention of alpha-KGDH activity at the expense
      of BCKDH activity. Thus, thiamin deficiency and excess cause large changes in
      mitochondrial TDP levels that have a major influence on the activities of the
      keto acid dehydrogenase complexes.

PMID- 10082769
TI  - Inhibition of glutathione synthesis with propargylglycine enhances N
      acetylmethionine protection and methylation in bromobenzene-treated Syrian
      hamsters.
AB  - The finding that liver necrosis caused by the environmental glutathione (GSH)
      depleting chemical, bromobenzene (BB) is associated with marked impairment in O-
      and S-methylation of BB metabolites in Syrian hamsters raises questions
      concerning the role of methyl deficiency in BB toxicity. N-Acetylmethionine (NAM)
      has proven to be an effective antidote against BB toxicity when given after liver
      GSH has been depleted extensively. The mechanism of protection by NAM may occur
      via a replacement of methyl donor and/or via an increase of GSH synthesis. If
      replacement of the methyl donor is an important process, then blocking the
      resynthesis of GSH in the methyl-repleted hamsters should not decrease NAM
      protection. This hypothesis was examined in this study. Propargylglycine (PPG),
      an irreversible inhibitor of cystathionase, was used to inhibit the utilization
      of NAM for GSH resynthesis. Two groups of hamsters were pretreated with an
      intraperitoneal (ip) dose of PPG (30 mg/kg) or saline 24 h before BB
      administration (800 mg/kg, ip). At 5 h after BB treatment, an ip dose of NAM
      (1200 mg/kg) was given. Light microscopic examinations of liver sections obtained
      24 h after BB treatment indicated that NAM provided better protection (P < 0.05)
      in the PPG + BB + NAM group than in the BB + NAM group. Liver GSH content,
      however, was lower in the PPG + BB + NAM group than in the BB + NAM group. The
      Syrian hamster has a limited capability to N-deacetylated NAM. The substitution
      of NAM with methionine (Met; 450 mg/kg) resulted in a higher level of GSH in the
      BB + Met group than in the BB + NAM group (P < 0.05). The enhanced protection by
      PPG in the PPG + BB + NAM group was accompanied by higher (P < 0.05) urinary
      excretions of specificO- and S-methylated bromothiocatechols than in the BB + NAM
      group. The results suggest that NAM protection occurs primarily via a replacement
      of the methyl donor and that methyl deficiency occurring in response to GSH
      repletion plays a potential role in BB toxicity.

PMID- 10082770
TI  - Heating garlic inhibits its ability to suppress 7, 12-dimethylbenz(a)anthracene
      induced DNA adduct formation in rat mammary tissue.
AB  - The present studies compared the impact of heating, either by microwave or
      convection oven, on the ability of garlic to reduce the in vivo bioactivation of
      7,12-dimethylbenz(a)anthracene (DMBA) in 55-d-old female Sprague-Dawley rats. In
      study 1, rats were fed a semipurified casein-based diet and treated by gastric
      gavage thrice weekly for 2-wk with crushed garlic (0.7 g in 2 mL corn oil) or the
      carrier prior to DMBA treatment (50 mg/kg body weight). Providing crushed garlic
      reduced by 64% (P < 0.05) the quantity DMBA-induced DNA adducts present in
      mammary epithelial cells compared to controls. In study 2, microwave treatment
      for 60 s, but not 30 s, decreased (P < 0.05) the protection provided by garlic
      against DMBA-induced adduct formation. In study 3, allowing crushed garlic to
      stand for 10 min prior to microwave heating for 60 s significantly (P < 0.05)
      restored its anticarcinogenic activity. Microwave heating of garlic for 30 s
      resulted in a 90% loss of alliinase activity. Heating in a convection oven (study
      4) also completely blocked the ability of uncrushed garlic to retard DMBA
      bioactivation. Study 5 revealed that providing either 0.105 micromol diallyl
      disulfide or S-allyl cysteine by gastric gavage thrice weekly for 2 wk was
      effective in retarding DMBA bioactivation but isomolar alliin was not. These
      studies provide evidence that alliinase may be important for the formation of
      allyl sulfur compounds that contribute to a depression in DMBA metabolism and
      bioactivation.

PMID- 10082771
TI  - Dietary nucleotide supplementation raises erythrocyte 2, 3-diphosphoglycerate
      concentration in neonatal rats.
AB  - The present study was designed to test if dietary intake of nucleotides increases
      erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in neonatal rats. To this end, rat
      pups were fed a nucleotide-supplemented formula (S, n = 14) from d 9 until d 16
      after birth. The results were compared with those obtained from a group of breast
      fed pups (C, n = 14) and a group of pups artificially fed with nucleotide-free
      formula (NS, n = 14). Neonatal weight, 2,3-DPG concentration, hematocrit (Hct)
      and hemoglobin concentration (Hb) were determined before the experiment (d 9) and
      after 7 d of treatment (d 16). In all groups, 2,3-DPG concentration was greater
      at d 16 than d 9, and the increase was greater in the S group than in the NS
      group. Alterations in neonatal weight, Hct and Hb concentration did not differ
      among the groups. On d 16 the 2, 3-DPG/Hb ratio, reflecting the affinity of
      hemoglobin for oxygen, was significantly higher in the C and S groups than in the
      NS group. We conclude that in neonatal rats, dietary nucleotides increase
      erythrocyte 2,3-DPG concentration. Studies need to be conducted in humans to
      assess the effect of this increase on both neonatal peripheral hemodynamics and
      metabolism in this species.

PMID- 10082772
TI  - Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American
      and Caucasian girls despite hormonal differences.
AB  - To assess the possibility of ethnic differences in mineral metabolism in
      prepubertal children, we compared measures of calcium metabolism in 7- and 8-y
      old Mexican-American (MA) and non-Hispanic Caucasian (CAU) girls (n = 38) living
      in southeastern Texas. We found similar fractional calcium absorption, urinary
      calcium excretion, calcium kinetic values and total-body bone mineral content in
      the MA and CAU girls. In contrast, parathyroid hormone (PTH) concentrations were
      greater in MA girls (4.01 +/- 0.47 vs. 1. 96 +/- 0.50 pmol/L, P = 0.005) than in
      CAU girls. Serum 25-hydroxyvitamin D concentrations were lower in MA girls (68.9
      +/- 7.7 vs. 109.4 +/- 8.4 nmol/L, P = 0.001) than in CAU girls, but 1, 25
      dihydroxyvitamin D concentrations did not differ between groups. Seasonal
      variability was seen for 25-hydroxyvitamin D concentrations in girls of both
      ethnic groups, but values in all of the girls were >30 nmol/L (12 ng/mL). We
      conclude the following: 1) greater PTH levels in MA girls than CAU girls are
      present without evidence of vitamin D deficiency; and 2) differences in 25
      hydroxyvitamin D and PTH concentrations between MA and CAU girls do not have a
      large effect on calcium absorption, excretion or bone calcium kinetics. These
      data do not provide evidence for adjusting dietary recommendations for mineral or
      vitamin D intake by MA girls.

PMID- 10082773
TI  - Women's dietary intakes in the context of household food insecurity.
AB  - A study of food insecurity and nutritional adequacy was conducted with a sample
      of 153 women in families receiving emergency food assistance in Toronto, Canada.
      Contemporaneous data on dietary intake and household food security over the past
      30 d were available for 145 of the women. Analyses of these data revealed that
      women who reported hunger in their households during the past 30 d also reported
      systematically lower intakes of energy and a number of nutrients. The effect of
      household-level hunger on intake persisted even when other economic, socio
      cultural, and behavioral influences on reported dietary intake were considered.
      Estimated prevalences of inadequacy in excess of 15% were noted for Vitamin A,
      folate, iron, and magnesium in this sample, suggesting that the low levels of
      intake associated with severe household food insecurity are in a range that could
      put women at risk of nutrient deficiencies.

PMID- 10082774
TI  - Caregiver behaviors and resources influence child height-for-age in rural Chad.
AB  - The purpose of this study was to identify caregiver characteristics that
      influence child nutritional status in rural Chad, when controlling for
      socioeconomic factors. Variables were classified according to the categories of a
      UNICEF model of care: caregiving behaviors, household food security, food and
      economic resources and resources for care and health resources. Sixty-four
      households with 98 children from ages 12 to 71 mo were part of this study.
      Caregivers were interviewed to collect information on number of pregnancies,
      child feeding and health practices, influence on decisions regarding child health
      and feeding, overall satisfaction with life, social support, workload, income,
      use of income, and household food expenditures and consumption. Household heads
      were questioned about household food production and other economic resources.
      Caregiver and household variables were classified as two sets of variables, and
      separate regression models were run for each of the two sets. Significant
      predictors of height-for-age were then combined in the same regression model.
      Caregiver influence on child-feeding decisions, level of satisfaction with life,
      willingness to seek advice during child illnesses, and the number of individuals
      available to assist with domestic tasks were the caregiver factors associated
      with children's height-for-age. Socioeconomic factors associated with children's
      height-for-age were the amount of harvested cereals, the sources of household
      income and the household being monogamous. When the caregiver and household
      socioeconomic factors were combined in the same model, they explained 54% of the
      variance in children's height-for-age, and their regression coefficients did not
      change or only slightly increased, except for caregiver's propensity to seek
      advice during child illnesses, which was no longer significant. These results
      indicate that caregiver characteristics influence children's nutritional status,
      even while controlling for the socioeconomic status of the household.

PMID- 10082775
TI  - Abbreviated measures of food sufficiency validly estimate the food security level
      of poor households: measuring household food security.
AB  - This study was designed to develop an abbreviated method that captures both the
      qualitative and quantitative dimensions of household food security (HFS). Women
      in poor and very poor households (n = 238) in a peri-urban barrio in Caracas,
      Venezuela, provided data on food availability and their perception of food
      resource constraints and hunger experiences within the home. Socioeconomic data
      and food-related behavior that may predict HFS levels were gathered. On average,
      the top 12 food contributors of energy provided 81% and predicted more than 90%
      of the variation in households' total energy availability using stepwise
      regression analysis. On the other hand, a 4-point 12-item scale was shown to have
      face, content and construct validity with reiterative testing, factor analysis
      and a Chronbach's alpha coefficient of 0.92. Assessing predictors of energy
      availability together with a self-perceived HFS scale may provide a valid and
      reliable method for identifying and monitoring food security levels among poor
      urban households.

PMID- 10082776
TI  - Chronic protein undernutrition and an acute inflammatory stimulus elicit
      different protein kinetic responses in plasma but not in muscle of piglets.
AB  - The changes in protein metabolism of severe childhood malnutrition are generally
      perceived as a metabolic adaptation to chronic protein undernutrition. However,
      severe malnutrition is invariably accompanied by infections which also have
      profound effects on protein metabolism. This study aimed to distinguish the
      effect of protein undernutrition from that of an inflammatory stimulus on muscle
      and plasma protein synthesis rates. Two groups of five piglets consumed diets
      containing either 23% or 3% protein for 4 wk. They then were infused
      intravenously with 2H3-leucine before and 48 h after subcutaneous injections of
      turpentine to measure the fractional synthesis rates (FSR) of muscle protein and
      both the FSR and the absolute synthesis rates (ASR) of albumin and fibrinogen.
      Prior to turpentine injection, compared to control piglets, protein-deficient
      piglets had significantly lower muscle FSR and plasma concentrations of both
      albumin and fibrinogen, although only albumin had lower FSR and ASR. Turpentine
      injection decreased muscle FSR but increased the FSR, ASR and plasma
      concentrations of both albumin and fibrinogen in control piglets. In protein
      deficient piglets, the inflammatory stress caused a further decrease in muscle
      protein FSR and in plasma albumin concentration despite marked increases in
      albumin FSR and ASR. Fibrinogen FSR, ASR and plasma concentration were increased.
      We conclude that protein undernutrition and inflammation elicit the same kinetic
      response in muscle protein but different kinetic responses in plasma proteins.
      Furthermore, whereas protein deficiency reduces the plasma albumin pool via a
      reduction in albumin synthesis, inflammation reduces it through a stimulation of
      catabolism and/or loss from the intravascular space.

PMID- 10082777
TI  - Alterations of lipid and cholesterol metabolism in cachectic tumor-bearing rats
      are prevented by insulin.
AB  - The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive
      body weight loss, associated with reduced food intake, and protein and lipid
      hypercatabolism. Because insulin regulates glucose as well as lipid and protein
      metabolism, we suggest that the observed alterations are at least in part
      secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones
      in AH130-bearing rats. To verify this hypothesis, controls with free access to
      food (n = 4), controls with free access to food plus insulin (107 micromol. kg
      body wt-1. d-1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4),
      pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor
      hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells
      ( approximately 10(8) cells/rat) were inoculated intraperitoneally. Daily food
      intake and body weight were measured; insulin was injected starting the day of
      tumor implantation for 6 d. The metabolism of both cholesterol and lipids was
      investigated in tumor cells, and ascitic fluid and blood serum were investigated
      at the end of treatment. Insulin prevented the reduction of food intake (19 +/-
      0.6 vs. 13 +/- 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with
      insulin, respectively), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P <
      0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1
      mmol/L, P < 0.01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P <
      0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240
      +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin
      prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mmol/L,
      P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated
      by 14C-acetate incorporation into cholesterol, in both liver (3,337 +/- 245 vs.
      830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,693 vs. 4,196 +/- 527
      Bq/10(6) cells, P < 0.01). Thus insulin treatment ameliorated many metabolic
      derangements, with a lengthening of rats survival time (7 +/- 1 vs. 11 +/- 1 d, P
      < 0.05) without significantly stimulating tumor growth. These data, together with
      our previous observations on the effectiveness of insulin on protein turnover
      perturbations, suggest that many metabolic alterations occurring during cancer
      cachexia can be avoided by the administration of this hormone.

PMID- 10082778
TI  - Calcium does not inhibit iron absorption or alter iron status in infant piglets
      adapted to a high calcium diet.
AB  - The purpose of this study was to investigate whether a dietary calcium:iron ratio
      similar to that often consumed by premature human infants inhibits iron
      absorption in infant piglets adapted to a high calcium diet. Male Yorkshire
      piglets were randomized at 3 to 4 d of age to a high calcium diet (4.67 g/L = HC)
      or a normal calcium diet (2.0 g/L = NC) and fed for 2 to 2.5 wk. An iron dextran
      injection was administered in amounts to achieve a marginal state of iron
      repletion to simulate iron status of premature infants. In vivo iron absorption
      from the diet was determined using the radiotracers 55Fe and 59Fe and whole body
      counting. Calcium:iron interactions at absorption sites in piglets fed HC and NC
      were investigated by measurements of time-dependent 59Fe uptake in response to
      different calcium:iron ratios in vitro in brush border membrane vesicles (BBMV).
      In vivo iron absorption from the diet did not differ between NC and HC diet
      groups [57 +/- 8% versus 55 +/- 17% (mean +/- SD), respectively]. Iron status and
      iron contencentrations in spleen, liver, intestine, kidney and heart did not
      differ between diet groups. Iron uptake in BBMV was significantly reduced by
      calcium in both HC and NC (P < 0.001); but there were no significant differences
      in iron uptake in response to different calcium:iron ratios between HC and NC.
      With feeding a HC diet for 2 wk there may be an adaptive response to counteract
      the inhibitory effects of calcium on iron absorption, thus resulting in similar
      in vivo iron absorption and iron status irrespective of the 1.3-fold difference
      in dietary calcium:iron ratio between piglet groups. However, future studies are
      needed to determine the specific sites of calcium:iron interactions and
      adaptation mechanisms. Since the calcium:iron ratios used in this study reflect
      the usual calcium:iron ratios in diets for premature infants, it is unlikely that
      interactive effects of calcium with iron will compromise iron status in this
      infant population when diets are supplemented with calcium.

PMID- 10082779
TI  - Folate nutriture alters choline status of women and men fed low choline diets.
AB  - Choline and folate share methylation pathways and, in studies of rats, were shown
      to be metabolically inter-related. To determine whether choline status is related
      to folate intake in humans, we measured the effect of controlled folate depletion
      and repletion on the plasma choline and phosphatidylcholine concentrations of 11
      healthy men (33-46 y) and 10 healthy women (49-63 y) fed low-choline diets in two
      separate metabolic unit studies. Total folate intake was varied by supplementing
      low folate (25 and 56 microg/d for men and women, respectively) and low choline
      (238 and 147 mg/d for men and women, respectively) diets with pteroylglutamic
      acid for 2-6 wk following folate-depletion periods of 4-5 wk. The low
      folate/choline intakes resulted in subclinical folate deficiencies; mean plasma
      choline decreases of 28 and 25% in the men and women, respectively; and a plasma
      phosphatidylcholine decrease of 26% in the men (P < 0. 05). No functional choline
      deficiency occurred, as measured by serum transaminase and lipid concentrations.
      The decreases in choline status measures returned to baseline or higher upon
      moderate folate repletion and were more responsive to folate repletion than
      plasma folate and homocysteine. Feeding methionine supplements to the men did not
      prevent plasma choline depletion, indicating that folate is a more limiting
      nutrient for these methylation pathways. The results indicate that 1) choline is
      utilized as a methyl donor when folate intake is low, 2) the de novo synthesis of
      phosphatidylcholine is insufficient to maintain choline status when intakes of
      folate and choline are low, and 3) dietary choline is required by adults in an
      amount > 250 mg/d to maintain plasma choline and phosphatidylcholine when folate
      intake is low.

PMID- 10082780
TI  - Dietary pantothenic acid requirement of juvenile grass shrimp, Penaeus monodon.
AB  - A feeding trial was conducted to estimate the minimal dietary pantothenic acid
      (PA) requirement for juvenile grass shrimp, Penaeus monodon. Purified diets with
      seven levels (0, 20, 40, 60, 120, 240, and 480 mg/kg) of supplemental PA were fed
      to P. monodon (mean weight 0.88 +/- 0.01 g) for 8 wk. The level of PA detected in
      the unsupplemented diet was 0.02 mg/kg. Each diet was fed to three replicate
      groups of shrimp. Feed efficiencies (FE) and protein efficiency ratios were
      highest in shrimp fed the diets supplemented with 120, 240, and 480 mg PA/kg
      diet, followed by the groups fed 60 mg/kg, then 40 mg/kg, and finally the
      unsupplemented control group (P < 0.05). Shrimp fed diets supplemented with PA
      had significantly higher survival percentages and lower hepatopancreatic lipid
      concentration than those fed the unsupplemented, control diets. Broken-line
      regression analyses of weight gain percentage and hepatopancreatic CoA and PA
      concentrations of the shrimp indicated that the adequate dietary PA concentration
      in growing P. monodon is 101-139 mg/kg.

PMID- 10082781
TI  - Human extracellular water volume can be measured using the stable isotope
      Na234SO4.
AB  - The volume of human extracellular water (ECW) may be estimated from the sulfate
      space (SS). Although it may better approximate ECW volume than the bromide space,
      a common alternative, SS measurement is limited by the need to administer a
      radioactive substance, sodium [35S]sulfate. In this paper, we demonstrate the
      measurement of the SS using the stable isotope, sodium [34S]sulfate. Eight
      healthy nonobese men ingested 0.50-0.78 mg (3.47-5.42 micromol) Na234SO4/kg body
      weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34SO4
      enrichments were measured by electrospray tandem mass spectrometry before and
      during the 5 h after tracer administration. SS was calculated by linear
      extrapolation of the natural logarithm of serum 34SO4 concentrations obtained at
      h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3
      and 5 (187 +/- 17 mL/kg) was similar to published determinations using
      intravenous or oral radiosulfate, and was 80% of the simultaneously measured
      corrected bromide space (234 +/- 10 mL/kg, P = 0.01). Oral sodium [34S]sulfate
      administration is a suitable technique for measuring ECW and avoids radiation
      exposure.

PMID- 10082782
TI  - A model of whole-body protein turnover based on leucine kinetics in rodents.
AB  - The measurement of fractional synthesis rate is based on the following
      assumptions: amino acids for protein synthesis are supplied by an intracellular
      pool; amino acids from protein degradation are not recycled preferentially to
      protein synthesis; and proteins turn over at a homogeneous rate. To test these
      assumptions, a mechanistic, theoretical model of protein turnover for a
      nongrowing 26-g mouse was developed on the basis of data from the literature. The
      model consisted of three protein pools turning over at fast (102 micromol Leu,
      t1/2= 11.5 h), medium (212 micromol Leu, t1/2 = 16.6 h) or slow (536 micromol
      Leu, t1/2 = 71.5 h) rates and extracellular (1.69 micromol Leu), leucyl-tRNA
      (0.0226 micromol Leu) and intracellular (5.72 micromol Leu) amino acid pools that
      exchanged amino acids. The flow of amino acids from the protein pools to the
      leucyl-tRNA pool determined the amount of recycling. The flow of amino acids from
      the extracellular pool to aminoacyl tRNA determined the amount of channeling. Two
      flooding dose data sets were used to evaluate specific radioactivity changes
      predicted by the model. Predictions of specific radioactivities using flooding
      dose, pulse dose or continuous infusion methods indicated that the model can be a
      useful tool in estimating the rates of channeling and recycling. However, it was
      found that use of data from flooding dose experiments might cause inaccurate
      predictions of certain fluxes.

PMID- 10082783
TI  - Recycling, channeling and heterogeneous protein turnover estimation using a model
      of whole-body protein turnover based on leucine kinetics in rodents.
AB  - In the companion paper, a whole-body, mechanistic model of protein turnover in a
      rodent was described and evaluated with independent data sets that used the
      flooding dose method. On the basis of fitted fluxes, the model was able to
      predict specific radioactivity changes in the protein and free leucine pools and
      whole-body protein fractional synthesis rate (FSR). In this paper, results of
      model simulations of specific radioactivity changes in the flooding dose, pulse
      dose and continuous infusion methods were compared and the influence of
      recycling, channeling and multiple protein pools on model behavior were analyzed.
      For all methods, the percentage of channeling must be estimated to determine
      whether the extracellular or intracellular pool specific radioactivities better
      approximate the aminoacyl tRNA pool specific radioactivity. Recycling also
      affects the specific radioactivity of the aminoacyl-tRNA pool and therefore must
      be estimated. An analysis of fits of the flooding dose data indicated that 100%
      channeling was occurring, but the percentage of recycling could not be
      determined. Multiple protein pools turning over at different rates overestimated
      FSR by 2-3% at early time points (5 min) and underestimated FSR by 3-6% at 60 min
      in the flooding dose method. For the pulse dose method, FSR was underestimated by
      40-50% at 5 min and underestimated by 9-10% at 60 min. An increase in time to
      measure FSR caused a decrease in the estimate of FSR (18% over 3 h) for the
      flooding dose method and an increase in the estimate of FSR (144% over 3 h) for
      the pulse dose method.

PMID- 10082784
TI  - Modified Food Guide Pyramid for people over seventy years of age.

PMID- 10082785
TI  - Phytochemicals: biochemistry and physiology. Introduction.

PMID- 10082786
TI  - Dietary isoflavones: biological effects and relevance to human health.
AB  - Substantial evidence indicates that diets high in plant-based foods may explain
      the epidemiologic variance of many hormone-dependent diseases that are a major
      cause of mortality and morbidity in Western populations. There is now an
      increased awareness that plants contain many phytoprotectants. Lignans and
      isoflavones represent two of the main classes of phytoestrogens of current
      interest in clinical nutrition. Although ubiquitous in their occurrence in the
      plant kingdom, these bioactive nonnutrients are found in particularly high
      concentrations in flaxseeds and soybeans and have been found to have a wide range
      of hormonal and nonhormonal activities that serve to provide plausible mechanisms
      for the potential health benefits of diets rich in phytoestrogens. Data from
      animal and in vitro studies provide convincing evidence for the potential of
      phytoestrogens in influencing hormone-dependent states; although the clinical
      application of diets rich in these estrogen mimics is in its infancy, data from
      preliminary studies suggest beneficial effects of importance to health. This
      review focuses on the more recent studies pertinent to this field and includes,
      where appropriate, the landmark and historical literature that has led to the
      exponential increase in interest in phytoestrogens from a clinical nutrition
      perspective.

PMID- 10082787
TI  - Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism.
AB  - Substantial quantities of isothiocyanates are released upon consumption of normal
      amounts of a number of cruciferous vegetables. Some of these naturally occurring
      isothiocyanates such as phenethyl isothiocyanate (PEITC), benzyl isothiocyanate
      (BITC) and sulforaphane are effective inhibitors of cancer induction in rodents
      treated with carcinogens. A large amount of data demonstrate that isothiocyanates
      act as cancer chemopreventive agents by favorably modifying carcinogen metabolism
      via inhibition of Phase 1 enzymes and/or induction of Phase 2 enzymes. These
      effects are quite specific, depending on the structure of the isothiocyanate and
      carcinogen. One of the most thoroughly studied examples of isothiocyanate
      inhibition of rodent carcinogenesis is inhibition of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK)-induced lung tumorigenesis by PEITC. This occurs
      because PEITC blocks the metabolic activation of NNK, resulting in increased
      urinary excretion of detoxified metabolites. Similar effects on NNK metabolism
      have been observed in smokers who consumed watercress, a source of PEITC. On the
      basis of these observations and knowledge of the carcinogenic constituents of
      cigarette smoke, a strategy for chemoprevention of lung cancer can be developed.

PMID- 10082788
TI  - Prevention and therapy of cancer by dietary monoterpenes.
AB  - Monoterpenes are nonnutritive dietary components found in the essential oils of
      citrus fruits and other plants. A number of these dietary monoterpenes have
      antitumor activity. For example, d-limonene, which comprises >90% of orange peel
      oil, has chemopreventive activity against rodent mammary, skin, liver, lung and
      forestomach cancers. Similarly, other dietary monoterpenes have chemopreventive
      activity against rat mammary, lung and forestomach cancers when fed during the
      initiation phase. In addition, perillyl alcohol has promotion phase
      chemopreventive activity against rat liver cancer, and geraniol has in vivo
      antitumor activity against murine leukemia cells. Perillyl alcohol and d-limonene
      also have chemotherapeutic activity against rodent mammary and pancreatic tumors.
      As a result, their cancer chemotherapeutic activities are under evaluation in
      Phase I clinical trials. Several mechanisms of action may account for the
      antitumor activities of monoterpenes. The blocking chemopreventive effects of
      limonene and other monoterpenes during the initiation phase of mammary
      carcinogenesis are likely due to the induction of Phase II carcinogen
      metabolizing enzymes, resulting in carcinogen detoxification. The post-initiation
      phase, tumor suppressive chemopreventive activity of monoterpenes may be due to
      the induction of apoptosis and/or to inhibition of the post-translational
      isoprenylation of cell growth-regulating proteins. Chemotherapy of chemically
      induced mammary tumors with monoterpenes results in tumor redifferentiation
      concomitant with increased expression of the mannose-6-phosphate/insulin-like
      growth factor II receptor and transforming growth factor beta1. Thus,
      monoterpenes would appear to act through multiple mechanisms in the
      chemoprevention and chemotherapy of cancer.

PMID- 10082789
TI  - Expression of the ADP/ATP carrier encoding genes in aerobic yeasts; phenotype of
      an ADP/ATP carrier deletion mutant of Schizosaccharomyces pombe.
AB  - The expression of a key mitochondrial membrane component, the ADP/ATP carrier,
      was investigated in two aerobic yeast species, Kluyveromyces lactis and
      Schizosaccharomyces pombe. Although the two species differ very much in their
      respiratory capacity, the expression of the carrier in both yeast species was
      decreased under partially anaerobic conditions and was induced by nonfermentable
      carbon sources. The single ADP/ATP carrier encoding gene was deleted in S. pombe.
      The null mutant exhibits impaired growth properties, especially when cultivated
      at reduced oxygen tension, and is unable to grow on a nonfermentable carbon
      source. Our results suggest that the inability of K. lactis and S. pombe to grow
      under anaerobic conditions can be related in part to the absence of a functional
      ADP/ATP carrier due to repression of the corresponding gene expression.

PMID- 10082790
TI  - Aromatic amino acids in the Rieske iron-sulfur protein do not form an obligatory
      conduit for electron transfer from the iron-sulfur cluster to the heme of
      cytochrome c1 in the cytochrome bc1 complex.
AB  - We have changed nine conserved aromatic amino acids by site-directed mutagenesis
      of the cloned iron-sulfur protein gene to determine if any of these residues form
      an obligatory conduit for electron transfer within the iron-sulfur protein of the
      yeast cytochrome bc1 complex. The residues include W111, F117, W152, F173, W176,
      F177, H184, Y205 and F207. Greater than 70% of the catalytic activity was
      retained for all of the mutated iron-sulfur proteins, except for those containing
      a W152L and a W176L-F177L double mutation, for which the activity was
      approximately 45%. The crystal structures of the bc1 complex indicate that F177
      and H184 are at the surface of the iron-sulfur protein near the surface of
      cytochrome c1, but not directly in a linear pathway between the iron-sulfur
      cluster and the c1 heme. The pre-steady-state rates of reduction of cytochromes b
      and c1 in mutants in which F177 and H184 were changed to non-aromatic residues
      were approximately 70-85% of the wild-type rates. There was a large decrease in
      iron-sulfur protein levels in mitochondrial membranes resulting from the W152L
      mutation and the W176L-F177L double mutation, and a small decrease for the Y205L,
      W176L and F177L mutations. This indicates that the decreases in activity
      resulting from these amino acid changes are due to instability of the altered
      proteins. These results show that these aromatic amino acids are unnecessary for
      electron transfer, but several are required for structural stability.

PMID- 10082791
TI  - Proton to electron stoichiometry in electron transport of spinach thylakoids 
AB  - According to the concept of the Q-cycle, the H+/e- ratio of the electron
      transport chain of thylakoids can be raised from 2 to 3 by means of the
      rereduction of plastoquinone across the cytochrome b6f complex. In order to
      investigate the H+/e- ratio we compared stationary rates of electron transport
      and proton translocation in spinach thylakoids both in the presence of the
      artificial electron acceptor ferricyanide and in the presence of the natural
      acceptor system ferredoxin+NADP. The results may be summarised as follows: (1) a
      variability of the H+/e- ratio occurs with either acceptor. H+/e- ratios of 3 (or
      even higher in the case of the natural acceptor system, see below) are decreased
      towards 2 if strong light intensity and low membrane permeability are employed.
      Mechanistically this could be explained by proton channels connecting the
      plastoquinol binding site alternatively to the lumenal or stromal side of the
      cytochrome b6f complex, giving rise to a proton slip reaction at high
      transmembrane DeltapH. In this slip reaction protons are deposited on the stromal
      instead of the lumenal side. In addition to the pH effect there seems to be a
      contribution of the redox state of the plastoquinone pool to the control of
      proton translocation; switching over to stromal proton deposition is favoured
      when the reduced state of plastoquinone becomes dominant. (2) In the presence of
      NADP a competition of both NADP and oxygen for the electrons supplied by
      photosystem I takes place, inducing a general increase of the H+/e- ratios above
      the values obtained with ferricyanide. The implications with respect to the
      adjustment of a proper ATP/NADPH ratio for CO2 reduction are discussed.

PMID- 10082792
TI  - Identification of
AB  - [8-vinyl]-Protochlorophyllide a1 was isolated from a Prochloron sp. associated
      with the host ascidian, Lissoclinum patella. To obtain sufficient amounts for
      identification of the purified pigment, suitable extraction procedures and HPLC
      systems were developed. The structure was finally elucidated by UV-VIS and
      fluorescence spectroscopy, mass spectrometry and NMR (rotating-frame Overhauser
      enhancement spectroscopy). [8-vinyl]-Protochlorophyllide a was originally
      detected only as an intermediate in chlorophyll biosynthesis. Although its
      presence as a light-harvesting pigment was previously suggested in some
      prochlorophytes and eukaryotic algae, this is the first unequivocal demonstration
      of [8-vinyl]-protochlorophyllide a in an oxygenic phototroph. We also show that
      [8-vinyl]-protochlorophyllide a occurs in Prochloron species of four other
      ascidians as well as in Micromonas pusilla and Prochlorococcus marinus. The
      possible role of this pigment in photosynthesis is discussed.

PMID- 10082793
TI  - Restoration of the high-potential form of cytochrome b559 of photosystem II
      occurs via a two-step mechanism under illumination in the presence of manganese
      ions 
AB  - Spinach photosystem II membranes that had been depleted of the Mn cluster
      contained four forms of cytochrome (Cyt) b559, namely, high-potential (HP), HP',
      intermediate-potential (IP) and low-potential (LP) forms that exhibited the redox
      potentials of +400, +310, +170 and +35 mV, respectively, in potentiometric
      titration. When the membranes were illuminated with flashing light in the
      presence of 0.1 mM Mn2+, the IP form was converted to the HP' form by two flashes
      and then the HP' form was converted to the HP form by an additional flash. The
      quantum efficiency of the first conversion appeared to be quite high since the
      conversion was almost complete after two flashes. By contrast, the second
      conversion proceeded with low quantum efficiency and 40 flashes were required for
      completion. The effects of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)
      suggested that the first conversion did not require electron transfer from QA to
      QB while the second conversion had an absolute requirement for it. It was also
      suggested that the first conversion involved the reduction of the heme of Cyt
      b559, probably by QA-, and we propose that direct reduction by QA- induces a
      shift in the redox potential of the heme. The second conversion was also
      accompanied by the reduction of heme but it appeared that this conversion did not
      necessarily involve the reduction. The effects of DCMU on the reduction of heme
      suggested that the heme became reducible by QB- after the first conversion had
      been completed. This observation implies that the efficiency of electron transfer
      from QA to QB increased upon the conversion of the IP form to the HP' form, and
      we propose that restoration of the high-potential forms of Cyt b559 itself acts
      to make the acceptor side of photosystem II functional.

PMID- 10082794
TI  - The green fluorescent protein targets secretory proteins to the yeast vacuole 
AB  - The green fluorescent protein (GFP) was used as a marker to study the
      intracellular transport of vacuolar and secretory proteins in yeast. Therefore,
      the following gene constructs were expressed in Saccharomyces cerevisiae under
      control of the GAL1 promoter: GFP N-terminally fused to the yeast secretory
      invertase (INV-GFP), the plant vacuolar chitinase (CHN-GFP) and its secretory
      derivative (CHNDeltaVTP-GFP), which did not contain the vacuolar targeting
      peptide (VTP), both chitinase forms (CHN and CHNDeltaVTP), GFP without any
      targeting information and two secretory GFP variants with and without the VTP of
      chitinase (N-GFP-V and N-GFP). Whereas chitinase without VTP is accumulated in
      the culture medium the other gene products are retained inside the cell up to 48
      h of induction. Independently of a known VTP they are transported to the vacuole,
      so far as they contain a signal peptide for entering the endoplasmic reticulum.
      This was demonstrated by confocal laser scanning microscopy, immunocytochemical
      analysis and subcellular fractionation experiments as well. The transport of the
      GFP fusion proteins is temporary delayed by a transient accumulation in electron
      dense structures very likely derived from the ER, because they also contain the
      ER chaperone Kar2p/Bip. Our results demonstrate that GFP directs secretory
      proteins without VTP to the yeast vacuole, possibly by the recognition of an
      unknown vacuolar signal and demonstrates, therefore, a first limitation for the
      application of GFP as a marker for the secretory pathway in yeast.

PMID- 10082795
TI  - Contact hypersensitivity: a simple model for the characterization of disease-site
      targeting by liposomes.
AB  - A murine model of delayed-type hypersensitivity (DTH) is characterized with
      respect to liposome accumulation at a site of inflammation. Mice were sensitized
      by painting the abdominal region with a solution of 2,4-dinitrofluorobenzene
      (DNFB) and inflammation was induced 5 days later by challenging the ear with a
      dilute solution of DNFB. The inflammatory response was readily monitored by
      measuring ear thickness (edema) and radiolabeled leukocyte infiltration. Maximum
      ear swelling and cellular infiltration occurred 24 h after the epicutaneous
      challenge with the ear returning to normal size after approximately 72 h. We
      demonstrate that large unilamellar vesicles (LUV) accumulate at the site of
      inflammation to a level more than 20-fold higher than that measured in the
      untreated ear. Vesicle delivery to the ear correlated with increased vascular
      leakage resulting from endothelium remodeling in response to DNFB challenge, and
      was not a consequence of increased local tissue blood volume. Extravasation
      occurred only during the first 24 h after ear challenge; after this time the
      permeability of the endothelium to vesicles returned to normal. We further showed
      that LUV with a diameter of 120 nm exhibit maximum levels of accumulation, that a
      polyethylene glycol surface coating does not increase delivery, and that the
      process can be inhibited by the application of topical corticosteroids at the
      time of induction. These data and the inflammation model are discussed with
      respect to developing lipid-based drug delivery vehicles designed to accumulate
      at inflammatory disease sites.

PMID- 10082796
TI  - Modulation of polymorphic properties of dielaidoylphosphatidylethanolamine by the
      antineoplastic ether lipid 1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine.
AB  - The capacity of the antineoplastic ether lipid 1-O-octadecyl-2-O-methyl-glycero-3
      phosphocholine (ET-18-OCH3) to modulate the polymorphic properties of
      dielaidoylphosphatidylethanolamine has been studied using biophysical techniques.
      Differential scanning calorimetry showed that ET-18-OCH3 depresses the onset of
      the Lbeta to Lalpha phase transition, decreasing also DeltaH of the transition.
      At the same time, the onset of the transition from Lalpha to inverted hexagonal
      HII phase was gradually increased as the ether lipid concentration was increased,
      totally disappearing at concentrations higher than 5 mol%. Small-angle X-ray
      diffraction and 31P-NMR confirmed that ET-18-OCH3 induced that the appearance of
      the inverted hexagonal HII phase was shifted towards higher temperatures
      completely disappearing at concentrations higher than 5 mol%. These results were
      used to elaborate a partial phase diagram and they were discussed as a function
      of the molecular action of ET-18-OCH3.

PMID- 10082797
TI  - Differential scanning calorimetric study of the effect of the antimicrobial
      peptide gramicidin S on the thermotropic phase behavior of phosphatidylcholine,
      phosphatidylethanolamine and phosphatidylglycerol lipid bilayer membranes.
AB  - We have studied the effects of the antimicrobial peptide gramicidin S (GS) on the
      thermotropic phase behavior of large multilamellar vesicles of
      dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylethanolamine (DMPE)
      and dimyristoyl phosphatidylglycerol (DMPG) by high-sensitivity differential
      scanning calorimetry. We find that the effect of GS on the lamellar gel to liquid
      crystalline phase transition of these phospholipids varies markedly with the
      structure and charge of their polar headgroups. Specifically, the presence of
      even large quantities of GS has essentially no effect on the main phase
      transition of zwitterionic DMPE vesicles, even after repeating cycling through
      the phase transition, unless these vesicles are exposed to high temperatures,
      after which a small reduction in the temperature, enthalpy and cooperativity of
      the gel to liquid-crystalline phase transitions is observed. Similarly, even
      large amounts of GS produce similar modest decreases in the temperature, enthalpy
      and cooperativity of the main phase transition of DMPC vesicles, although the
      pretransition is abolished at low peptide concentrations. However, exposure to
      high temperatures is not required for these effects of GS on DMPC bilayers to be
      manifested. In contrast, GS has a much greater effect on the thermotropic phase
      behavior of anionic DMPG vesicles, substantially reducing the temperature,
      enthalpy and cooperativity of the main phase transition at higher peptide
      concentrations, and abolishing the pretransition at lower peptide concentrations
      as compared to DMPC. Moreover, the relatively larger effects of GS on the
      thermotropic phase behavior of DMPG vesicles are also manifest without cycling
      through the phase transition or exposure to high temperatures. Furthermore, the
      addition of GS to DMPG vesicles protects the phospholipid molecules from the
      chemical hydrolysis induced by their repeated exposure to high temperatures.
      These results indicate that GS interacts more strongly with anionic than with
      zwitterionic phospholipid bilayers, probably because of the more favorable net
      attractive electrostatic interactions between the positively charged peptide and
      the negatively charged polar headgroup in such systems. Moreover, at comparable
      reduced temperatures, GS appears to interact more strongly with zwitterionic DMPC
      than with zwitterionic DMPE bilayers, probably because of the more fluid
      character of the former system. In addition, the general effects of GS on the
      thermotropic phase behavior of zwitterionic and anionic phospholipids suggest
      that it is located at the polar/apolar interface of liquid-crystalline bilayers,
      where it interacts primarily with the polar headgroup and glycerol-backbone
      regions of the phospholipid molecules and only secondarily with the lipid
      hydrocarbon chains. Finally, the considerable lipid specificity of GS
      interactions with phospholipid bilayers may prove useful in the design of peptide
      analogs with stronger interactions with microbial as opposed to eucaryotic
      membrane lipids.

PMID- 10082798
TI  - Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus
      oocytes.
AB  - The molecular mechanisms of organic cation transport by rat OCT2 was examined in
      the Xenopus oocyte expression system. When extracellular Na+ ions were replaced
      with K+ ions, uptake of tetraethylammonium (TEA) by OCT2-expressing oocytes was
      decreased, suggesting that TEA uptake by OCT2 is dependent on membrane potential.
      Kinetic analysis revealed that the decreased TEA uptake by ion substitution was
      caused at least in part by decreased substrate affinity. Acidification of
      extracellular buffer resulted in decreased uptake of TEA, whereas TEA efflux from
      OCT1- and OCT2-expressing oocytes was not stimulated by inward proton gradient,
      in consistent with basolateral organic cation transport in the kidney. Inhibition
      of TEA uptake by various organic cations revealed that apparent substrate
      spectrum of OCT2 was similar with that of OCT1. However, the affinity of
      procainamide to OCT1 was higher than that to OCT2. Uptake of 1-methyl-4
      phenylpyridinium was stimulated by OCT2 as well as OCT1, but uptake of
      levofloxacin, a zwitterion, was not stimulated by both OCTs. These results
      suggest that OCT2 is a multispecific organic cation transporter with the
      characteristics comparable to those of the basolateral organic cation transporter
      in the kidney.

PMID- 10082799
TI  - A novel strategy for the preparation of liposomes: rapid solvent exchange.
AB  - During the preparation of multi-component model membranes, a primary
      consideration is that compositional homogeneity should prevail throughout the
      suspension. Some conventional sample preparation methods pass the lipid mixture
      through an intermediary, solvent-free state. This is an ordered, solid state and
      may favor the demixing of membrane components. A new preparative method has been
      developed which is specifically designed to avoid this intermediary state. This
      novel strategy is called rapid solvent exchange (RSE) and entails the direct
      transfer of lipid mixtures between organic solvent and aqueous buffer. RSE
      liposomes require no more than a minute to prepare and manifest considerable
      entrapment volumes with a high fraction of external surface area. In
      phospholipid/cholesterol mixtures of high cholesterol content, suspensions
      prepared by more conventional methods reveal evidence of artifactual demixing,
      whereas samples prepared by rapid solvent exchange do not. The principles which
      may lead to artifactual demixing during conventional sample preparation are
      discussed.

PMID- 10082800
TI  - Resolution of the paradox of red cell shape changes in low and high pH.
AB  - The molecular basis of cell shape regulation in acidic pH was investigated in
      human erythrocytes. Intact erythrocytes maintain normal shape in the cell pH
      range 6.3-7.9, but invaginate at lower pH values. However, consistent with
      predicted pH-dependent changes in the erythrocyte membrane skeleton, isolated
      erythrocyte membranes evaginate in acidic pH. Moreover, intact cells evaginate at
      pH greater than 7.9, but isolated membranes invaginate in this condition.
      Labeling with the hydrophobic, photoactivatable probe 5-[125I]iodonaphthyl-1
      azide demonstrated pH-dependent hydrophobic insertion of an amphitropic protein
      into membranes of intact cells but not into isolated membranes. Based on
      molecular weight and on reconstitution experiments using stripped inside-out
      vesicles, the most likely candidate for the variably labeled protein is
      glyceraldehyde-3-phosphate dehydrogenase. Resealing of isolated membranes
      reconstituted both the shape changes and the hydrophobic labeling profile seen in
      intact cells. This observation appears to resolve the paradox of the
      contradictory pH dependence of shape changes of intact cells and isolated
      membranes. In intact erythrocytes, the demonstrated protein-membrane interaction
      would oppose pH-dependent shape effects of the spectrin membrane skeleton,
      stabilizing cell shape in moderately abnormal pH. Stabilization of erythrocyte
      shape in moderately acidic pH may prevent inappropriate red cell destruction in
      the spleen.

PMID- 10082801
TI  - Analysis of the membrane-interacting domains of myelin basic protein by
      hydrophobic photolabeling.
AB  - Myelin basic protein is a water soluble membrane protein which interacts with
      acidic lipids through some type of hydrophobic interaction in addition to
      electrostatic interactions. Here we show that it can be labeled from within the
      lipid bilayer when bound to acidic lipids with the hydrophobic photolabel 3
      (trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine (TID) and by two lipid
      photolabels. The latter included one with the reactive group near the
      apolar/polar interface and one with the reactive group linked to an acyl chain to
      position it deeper in the bilayer. The regions of the protein which interact
      hydrophobically with lipid to the greatest extent were determined by cleaving the
      TID-labeled myelin basic protein (MBP) with cathepsin D into peptides 1-43, 44
      89, and 90-170. All three peptides from lipid-bound protein were labeled much
      more than peptides from the protein labeled in solution. However, the peptide
      labeling pattern was similar for both environments. The two peptides in the N
      terminal half were labeled similarly and about twice as much as the C-terminal
      peptide indicating that the N-terminal half interacts hydrophobically with lipid
      more than the C-terminal half. MBP can be modified post-translationally in vivo,
      including by deamidation, which may alter its interactions with lipid. However,
      deamidation had no effect on the TID labeling of MBP or on the labeling pattern
      of the cathepsin D peptides. The site of deamidation has been reported to be in
      the C-terminal half, and its lack of effect on hydrophobic interactions of MBP
      with lipid are consistent with the conclusion that the N-terminal half interacts
      hydrophobically more than the C-terminal half. Since other studies of the
      interaction of isolated N-terminal and C-terminal peptides with lipid also
      indicate that the N-terminal half interacts hydrophobically with lipid more than
      the C-terminal half, these results from photolabeling of the intact protein
      suggest that the N-terminal half of the intact protein interacts with lipid in a
      similar way as the isolated peptide. The similar behavior of the intact protein
      to that of its isolated peptides suggests that when the purified protein binds to
      acidic lipids, it is in a conformation which allows both halves of the protein to
      interact independently with the lipid bilayer. That is, it does not form a
      hydrophobic domain made up from different parts of the protein.

PMID- 10082802
TI  - Kinetics of lactate and pyruvate transport in cultured rat myotubes.
AB  - Skeletal muscle transport of lactate and pyruvate was studied in primary cultures
      of rat myotubes, applying the pH-sensitive fluorescent indicator 2', 7'
      bis(carboxyethyl)-5(6)-carboxyfluorescein. The initial rate of decrease in
      intracellular pH (pHi) upon lactate or pyruvate incubation was used to determine
      total transport (carrier mediated and diffusion). Both lactate and pyruvate
      transport could be inhibited by a combination of 0.5 mM 4,4'
      diisothiocyanostilbene-2, 2'-disulfonic acid, 5 mM mersalyl and 10 mM alpha-cyano
      4-hydroxycinnamate. The kinetic parameters, Km and Vmax, for carrier-mediated
      transport of lactate were 9.9+/-1.1 mM and 0. 69+/-0.02 mmol l-1 s-1,
      respectively. For pyruvate, Km and Vmax were 4.4+/-1.3 mM and 0.30+/-0.05 mmol l
      1 s-1, respectively. The diffusion component of the total transport was 0.0040+/
      0.0005[S] (n=4) and 0.0048+/-0.0003[S] (n=4) for lactate and pyruvate,
      respectively. Furthermore, it was observed that the two monocarboxylate
      transporter isoforms present in mature skeletal muscles, MCT1 and MCT4 (formerly
      called MCT3 (M.C. Wilson, V.N. Jackson, C. Heddle, N.T. Price, H. Pilegaard, C.
      Juel, A. Bonen, I. Montgomery, O.F. Hutter, A.P. Halestrap, Lactic acid efflux
      from white skeletal muscle is catalyzed by the monocarboxylate transporter
      isoform MCT3, J. Biol. Chem. 273 (1998) 15920-15926)), were also expressed in
      primary culture of myotubes.

PMID- 10082803
TI  - Pharmacological interaction of the calcium channel blockers verapamil and
      flunarizine with the opioid system.
AB  - We evaluated the opioid antinociceptive mechanism of the calcium channel blockers
      verapamil and flunarizine in groups of mice with the hotplate test. Both produced
      a naloxone-sensitive dose-dependent analgesia. The antinociceptive effect of both
      was reversed by beta-FNA, (mu1 and mu2 antagonists), and both enhanced the
      antinociceptive activity of morphine, implying a role for mu receptors.
      Furthermore, since the analgesic effect of flunarizine, but not verapamil, was
      reversed by naloxonazine (mu1 antagonist), we suggest that the mu1 subtype is
      involved in flunarizine analgesia, but not in verapamil analgesia. Studies with
      the selective delta opioid agonist DPDPE and the selective antagonists
      naltrindole indicated that the antinociceptive activity of verapamil is also
      mediated by delta receptor agonistic activity (primarily following i.c.v.
      administration); flunarizine, by contrast, exhibited antagonistic activity at
      this receptor. Verapamil amplified the antinociceptive activity of kappa1
      (U50,488H) and kappa3 (nalorphine) agonists, but its known analgesic activity was
      inhibited only partially by the kappa1 antagonist Nor-BNI, indicating partial
      involvement of kappa1 receptor. Flunarizine, however, demonstrated antagonistic
      activity at both kappa1 and kappa3 receptors, with more prominent inhibitory
      activity at the latter one. These findings suggest that verapamil and flunarizine
      elicit analgesia at both the spinal and supraspinal levels. Verapamil's analgesia
      was explained by agonistic activity at the mu, delta and may also be kappa3
      receptor subtypes. Flunarizine exhibited a mixed agonistic-antagonistic opioid
      activity as shown by its agonistic activity at the mu1 receptor and antagonistic
      activity at delta, kappa1 and kappa3 receptor subtypes.

PMID- 10082804
TI  - Human somatosensory cortical activation strengths: comparison between males and
      females and age-related changes.
AB  - The amplitudes of many scalp-recorded evoked potential (EP) deflections are
      higher in females than in males, and in elderly than in young subjects. Since EPs
      critically depend on the electric conductivity of the cranium, it is not known
      whether these differences reflect age- and gender-dependent changes in the
      intensity of neuronal activation, or changes in the volume conductor. Evoked
      magnetic fields are not significantly affected by the conductivities of the
      cranial tissues and therefore reflect more directly the neuronal activation than
      EPs. We report here on the effects of age and gender on somatosensory evoked
      fields (SEFs) from the primary somatosensory cortex (SI) in 43 healthy subjects
      (21 males) aged from 20 to 73 years (males 51+/-18 years, females 51+/-14 years).
      The intensity of neuronal activation was estimated with equivalent current
      dipoles (ECDs) found at the peaks of the N20m, P35m and P60m deflections from the
      left SI after right median nerve stimulation. The peak latencies of N20m and P35m
      (but not of P60m) were shorter in females than in males. The N20m latency was
      positively correlated with age in males, but otherwise the latencies did not
      correlate with age. The ECD amplitudes did not differ between males and females
      for any of the deflections. The N20m ECD strength showed a significant positive
      correlation (r=0.39, p<0.01) with age while P35m and P60m ECD strengths did not.
      The results thus did not disclose gender differences in the activation strengths
      of the somatosensory cortex, implying that such differences in evoked potentials
      may possibly be due to gender differences in the volume conductor. On the other
      hand, the results suggest a slight age-related increase in cortical excitability.

PMID- 10082805
TI  - Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity:
      cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine
      transporter binding sites.
AB  - We investigated if repeated administration of cocaine, nicotine, dizocipline (MK
      801) and alcohol yields behavioral cross-sensitization between these agents.
      Swiss Webster mice received in their home cage one of the following
      intraperitoneal (i. p.) injections for 5 consecutive days: (a) saline, (b)
      cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e)
      ethanol (2.0 g/kg). After a 10-day drug free period, each group (n=30) was
      divided into three subgroups (n=10) and received challenge injections of either
      cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice
      were recorded in locomotor activity cages (test cage). Among the various drugs
      tested, only the cocaine and ethanol experienced mice developed sensitization to
      a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized
      response only to a challenge injection of MK-801. In a second experiment, mice in
      their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0
      g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after
      a 10-day drug free period. Both, cocaine and ethanol experienced mice developed
      marked sensitization to ethanol challenge compared with the saline experienced
      mice. Assessment of the densities of striatal dopamine transporter (DAT) sites
      (by [3H]mazindol binding) 11 days after the extinction of repeated treatment with
      either cocaine or ethanol revealed a significant increase (71-108%) in the number
      of DAT binding sites. Thus, among the various psychostimulants investigated in
      the present study cross-sensitization between cocaine and ethanol was only
      observed. The behavioral sensitization we measured was primarily 'drug
      dependent', rather than 'context-dependent', because animals were exposed to the
      test cage only once. The finding that cocaine- and ethanol-induced behavioral
      sensitization is associated with upregulation of striatal DAT binding sites
      supports the hypothesis that similar neural substrates are involved in the
      psychomotor/rewarding effects of cocaine and alcohol.

PMID- 10082806
TI  - Biotransformation of nociceptin/orphanin FQ by enzyme activity from morphine
      naive and morphine-treated cell cultures.
AB  - The biotransformation of nociceptin/orphanin FQ (NOFQ) by enzyme activity
      isolated from U1690 human lung carcinoma and SH-SY5Y human neuroblastoma cell
      lines, and from rat brain cortex cells in primary culture was investigated. The
      identification and quantification of the cleavage products were performed using
      electrospray ionization mass spectrometry linked to size-exclusion
      chromatography. The effect of chronic morphine treatment of the cells (5 days) on
      NOFQ biotransformation was also studied. It was found that major products
      generated from NOFQ were the amino-terminal peptides N1-9 and N1-13. The pattern
      of NOFQ biotransformation was quite similar for all three cell cultures. However,
      different proportions of the formed peptides were noted. The cleavage was
      inhibited by EDTA, PMSF, Hg2+, Cu2+ and Zn2+. Dynorphin A2-13 inhibited NOFQ
      cleavage in a manner suggesting competition of the two peptides for the same
      enzyme. Chronic morphine treatment of the cell cultures resulted in a substantial
      increase in the enzyme activity, leading to higher levels of the major fragments
      and accumulation of N1-12 and the shorter peptides N1-5, N1-6. Since the effect
      of morphine treatment of the cells was blocked by naloxone, it is likely that it
      was receptor specific. Taken together, the findings suggest that a
      metallosensitive endopeptidase, the activity of which is increased by chronic
      morphine treatment of the cells, is responsible for the biotransformation of NOFQ
      with fragments N1-9 and N1-13 being the major products.

PMID- 10082807
TI  - Ultrastructural confirmation of neuronal protection by melatonin against the
      neurotoxin 6-hydroxydopamine cell damage.
AB  - 6-Hydroxydopamine (6-OHDA) is a neurotoxin used in the induction of experimental
      Parkinson's disease in both animals and cultured neuronal cells. Biochemical and
      molecular approaches showed previously that low doses of 6-OHDA induced apoptosis
      in PC12 cells, while high doses of this neurotoxin induced necrosis. Melatonin
      has been shown to protect against the neuronal programmed cell death induced by 6
      OHDA, although it was not able to prevent the massive necrotic cellular death
      occurring after the addition of high doses of the neurotoxin. In the present
      work, we demonstrate by ultrastructural analysis that although low doses of 6
      OHDA induced apoptosis in PC12 cells, it also damaged the non-apoptotic cells,
      morphologically corresponding this damage to incipient and reversible necrotic
      lesions. When the doses of the neurotoxin increase, there are still apoptotic
      cells, although most of the cells show necrotic irreversible lesions. We also
      found that melatonin partially prevents the incipient necrotic lesions caused by
      low doses of 6-OHDA. The fact that melatonin was shown in previous work to
      prevent apoptosis caused by low doses of 6-OHDA, but not necrosis induced by high
      doses of the neurotoxin, seemed to indicate that this agent is only able to
      protect against apoptosis. However, our present results, melatonin preventing
      also the incipient necrotic neuronal lesions, suggest that this hormone may
      provide a general protection against cell death, suggesting that higher doses
      should be tried in order to prevent the necrotic cell death induced by high doses
      of the neurotoxin.

PMID- 10082808
TI  - Effect of hypothermia on kainic acid-induced limbic seizures: an
      electroencephalographic and 14C-deoxyglucose autoradiographic study.
AB  - The effect of body temperature on kainic acid (KA)-induced limbic seizures was
      examined in Wistar rats. In rats undergoing limbic seizure induced by 1 microgram
      intra-amygdaloid injection of KA, the post-injection latency of initial ictal
      discharges in the left amygdala was significantly longer in rats whose body
      temperature was lowered to 30 degrees C (2.55+/-0.94 min at 37 degrees C, 13.19+/
      5. 70 min at 30 degrees C; p=0.0017). The post-injection latency of initial ictal
      discharges in the left hippocampus was also significantly longer under the same
      conditions (23.68+/-9.96 min at 37 degrees C, 43.85+/-17.98 min at 30 degrees C;
      p=0.0253). The number of limbic seizures occurring in the first 2 h post
      injection was significantly lower in hypothermic rats (30.0+/-10.7 at 37 degrees
      C, 8.71+/-2.69 at 30 degrees C; p=0.0017), as was the total duration of limbic
      seizures over the same period (23.61+/-8.45 min at 37 degrees C, 10.30+/-4.48 min
      at 30 degrees C; p=0.0060). Local cerebral glucose utilization (LCGU), measured 2
      h post-injection, was significantly lower in hypothermic rats, mainly in the
      limbic structures. 14C-deoxyglucose autoradiograms showed decreased radiation
      density not only in the left amygdala and bilateral hippocampus, but also in the
      cerebral cortex of hypothermic rats. The results of the present experiment
      demonstrate that the use of hypothermia, which has been shown to be effective in
      the treatment of acute cerebral ischemia and brain injury, may also be effective
      in the treatment of status epileptics.

PMID- 10082809
TI  - Characterization of receptors for ciliary neurotrophic factor on rat hippocampal
      astrocytes.
AB  - We have identified by Scatchard analysis both high (124 pM, 14.4 x106
      sites/micrograms protein, 7600 sites/cell) and low (1.6 nM, 7.7x106
      sites/micrograms protein, 4100 sites/cell) affinity receptors for [125I]-rat
      ciliary neurotrophic factor (rCNTF) on astrocytes. Ligand competition studies
      showed that the binding of [125I]-rCNTF was effectively competed by rCNTF and
      human CNTF, but not by hLIF, mIL-6 or mIL-1B. Three proteins specifically crossed
      linked to [125I]-rCNTF, with the molecular weights of 190, 100, and 43 kDa, were
      immunoprecipitated by anti-rCNTF antibodies. Anti-LIFR or anti-gp130 antibodies
      immunoprecipitated the 100 and the 190 kDa proteins. CNTF induced the tyrosine
      phosphorylation of LIFR and gp130, as well as of proteins with the molecular
      weights of 88/91 and 42 kDa. The phosphorylation of the 88/91 kDa protein(s) was
      inhibited by pretreating the cells with staurosporine, 12-myristate 13-acetate
      phorbol (PMA), W7, chlorpromazine, or the intracellular Ca+2 chelator BAPTA/AM.
      In contrast, CNTF and PMA acted synergistically to induce the phosphorylation of
      two proteins with the molecular weights of 42 and 44 kDa. At later time points
      following CNTF treatment, c-fos messenger RNA and protein levels were increased.
      Collectively, these data indicate that hippocampal astrocytes express high
      affinity, biologically functional receptor complexes for CNTF.

PMID- 10082810
TI  - Mechanisms whereby nerve growth factor increases diacylglycerol levels in
      differentiating PC12 cells.
AB  - We previously showed indirectly that the increase in diacylglycerol (DAG) levels
      caused by exposing differentiating PC12 cells to nerve growth factor (NGF) must
      derive mainly from de novo synthesis and, to a lesser and transient extent, from
      the hydrolysis of [3H]phosphatidylinositol (PI). To explore further the
      biochemical mechanisms of this increase, we measured, in PC12 cells, DAG
      synthesis from glycerol or various fatty acids; its liberation from
      phosphatidylcholine (PC); and the activities of various enzymes involved in DAG
      production and metabolism. Among cells exposed to NGF (0-116 h), the labeling of
      DAG from [3H]glycerol peaked earlier than that of [3H]PC, and the specific
      radioactivity of [3H]glycerol-labeled DAG was much higher than those of the
      [3H]phospholipids, indicating that [3H]DAG synthesis precedes [3H]phospholipid
      synthesis. NGF treatment also increased (by 50-330%) the incorporation of
      monounsaturated ([3H]oleic acid) and polyunsaturated ([14C]linoleic acid or
      [3H]arachidonic acid) fatty acids into DAG, and, by 15-70%, into PC. NGF
      treatment increased the activities of long chain acyl-CoA synthetases (LCASs),
      including oleoyl-CoA synthetase and arachidonoyl-CoA synthetase, by 150-580% over
      control, but cholinephosphotransferase activity rose by only 60%, suggesting that
      the synthesis of DAG in the cells was increased to a greater extent than its
      utilization. NGF did not promote the breakdown of newly formed [3H]PC to [3H]DAG,
      nor did it consistently affect the activities of phospholipase C or D. NGF did
      increase phospholipase A2 activity, however the hydrolysis catalyzed by this
      enzyme does not liberate DAG. Hence the major source of the increased DAG levels
      in PC12 cells exposed to NGF appears to be enhanced de novo DAG synthesis,
      probably initiated by the activation of LCASs, rather than the breakdown of PC or
      PI.

PMID- 10082811
TI  - Thyrotropin-releasing hormone concentrations in different regions of the chicken
      brain and pituitary: an ontogenetic study.
AB  - The regional distribution of thyrotropin-releasing hormone (TRH) was studied in
      the chicken brain. The hypothalamus and the brain stem contained the highest
      concentration of TRH. Lower amounts were present in the telencephalon, the optic
      lobes and the cerebellum. Within the hypothalamus, TRH was most abundant in the
      median eminence. Other important TRH sites were the nucleus paraventricularis
      magnocellularis, nucleus periventricularis hypothalami, nucleus ventromedialis
      hypothalami, nucleus dorsomedialis hypothalami and nucleus preopticus
      periventricularis. On the 14th day of embryonic development (E14), TRH was mostly
      found in the brain stem. Towards hatching, TRH concentrations increased gradually
      in both the hypothalamic area and the brain stem. TRH concentrations in the
      telencephalon, optic lobes and cerebellum remained low. Pituitaries from E14 to
      E16 chickens were characterized by a high TRH concentration, whereas hypophyseal
      TRH concentrations dropped towards hatching. Our results support the hypothesis
      that TRH exerts both endocrine and neurocrine actions in the chicken. On the
      other hand, high pituitary TRH concentrations were present when hypothalamic
      concentrations were low and vice versa. Therefore, the chicken pituitary may
      function as an important source of TRH during early in ovo development at least
      until the moment hypothalamic control develops.

PMID- 10082812
TI  - Insulin-like growth factor-1 (IGF-1)-induced inhibition of growth hormone
      secretion is associated with sleep suppression.
AB  - The hypothalamic growth hormone (GH)-releasing hormone (GHRH) promotes non-rapid
      eye movement sleep (NREMS). Insulin-like growth factor-1 (IGF-1) acts as a
      negative feedback in the somatotropic axis inhibiting GHRH and stimulating
      somatostatin. To determine whether this feedback alters sleep, rats and rabbits
      were injected intracerebroventricularly (i.c.v.) with IGF-1 (5.0 and 0.25
      microgram, respectively) and the sleep-wake activity was studied. Compared to
      baseline (i.c.v. injection of physiological saline), IGF-1 elicited prompt
      suppressions in both NREMS and rapid eye movement sleep (REMS) in postinjection
      hour 1 in rats and rabbits. The intensity of NREMS (characterized by the slow
      wave activity of the EEG by means of fast-Fourier analysis) was significantly
      enhanced 7 to 11 h postinjection in rats. Plasma GH concentrations were measured
      in 30-min samples after i.c.v. IGF-1 injection in rats and a significant
      suppression of GH secretion was observed 30 min postinjection. The simultaneous
      inhibition of the somatotropic axis and sleep raises the possibility that the
      sleep alterations also result from an IGF-1-induced suppression of GHRH. The late
      increases in NREMS intensity are attributed to metabolic actions of IGF-1 or to a
      release of GHRH from the IGF-1-induced inhibition.

PMID- 10082813
TI  - Kir6.2 oligoantisense administered into the globus pallidus reduces apomorphine
      induced turning in 6-OHDA hemiparkinsonian rats.
AB  - ATP-sensitive inwardly rectifying potassium channels (KATPs) couple cell
      metabolism with its membrane potential. The best characterized KATP is the
      pancreatic KATP which is an heteromultimer of Kir6.2 and SUR1 protein subunits.
      KATPs are found in a variety of excitable cells, including neurons of the central
      nervous system. Basal ganglia (BG), especially in the substantia nigra (SN)
      reticulata and the globus pallidus (GP), have a high density of KATPs.
      Pharmacological modulation of the KATPs within the BG alters GABAergic activity
      and produces behavioural changes. However, the relatively high concentrations of
      drugs used might not have been entirely selective for the KATPs and may have
      acted at presynaptic nerve terminals as well as on the post-synaptic neurons. As
      an alternative means of examining the role of KATPs in regulating motor behavior,
      we used oligoantisense technology to diminish selectively Kir6.2 formation in the
      GP neurons. We then examined the effect of reduction in Kir6.2 expression on
      apomorphine-induced turning behavior in rats with unilateral 6-hydroxydopamine (6
      OHDA) lesions of the SN. Two weeks after injection of 6-OHDA, contralateral
      circling in response to apomorphine (0.25 mg/kg sc) was recorded. Kir6.2
      antisense oligodeoxyribonucleotide (ODN) was then administered daily for 6 days
      into the GP ipsilateral to the 6-OHDA injection. Responses to apomorphine were
      then tested again and the animals killed to determine the effect of the antisense
      ODN on Kir6. 2 mRNA. Administration of Kir6.2 antisense ODN significantly
      attenuated apomorphine-induced contralateral turning and specifically reduced
      Kir6.2 mRNA in the injected GP. These results are consistent with pharmacological
      experiments which suggest that KATP channels in the GP are involved in motor
      responses to apomorphine in 6-OHDA lesioned rats, localizing the effects to the
      GP neurons, probably through modulation of the GABAergic system.

PMID- 10082814
TI  - Myelinated afferents sprout into lamina II of L3-5 dorsal horn following chronic
      constriction nerve injury in rats.
AB  - In order to investigate the consequences of chronic constriction injury (CCI) to
      nerve, we explored the relationship between the development of mechanical
      allodynia and the reorganization of primary afferent terminals in the sensory
      lamina of the rat spinal cord dorsal horn. Following sciatic CCI neuropathy,
      mechanical allodynia developed in the corresponding footpad within two weeks and
      persisted throughout the experimental period which extended for an additional two
      weeks. The neuropathy of the sciatic injury includes extensive Wallerian-like
      degeneration of myelinated fibers but relative sparing of unmyelinated fibers. We
      observed that there was no significant change in the dorsal horn termination of
      unmyelinated C fibers in lamina II of the dorsal horn, using nerve injections of
      wheat germ agglutin-horseradish peroxidase for transganglionic axonal tracing of
      these fibers from the nerve injury site, and no evidence of sprouting into
      adjacent lamina. In contrast, myelinated afferent fibers were observed to be
      sprouting into lamina II of the dorsal horn, as indicated by cholera toxin beta
      subunit-horseradish peroxidase retrograde axonal tracings. This region of the
      dorsal horn is associated with nociceptive-specific neurons that are not
      generally associated with myelinated fiber input from mechanical and
      proprioceptive receptors. As previously suggested in nerve transection and crush
      injuries, and now demonstrated in CCI neuropathy, these morphological changes may
      have significance in the pathogenesis of chronic mechanical allodynia.

PMID- 10082815
TI  - Behavioral and neurochemical consequences of lipopolysaccharide in mice:
      anxiogenic-like effects.
AB  - Systemic administration of lipopolysaccharide (LPS) induces sickness behaviors,
      as well as alterations of hypothalamic-pituitary-adrenal functioning commonly
      associated with stressors. In the present investigation, it was demonstrated that
      systemic LPS treatment induced a sickness-like behavioral profile (reduced active
      behaviors, soporific effects, piloerection, ptosis), which appeared to be
      dependent upon the novelty of the environmental context in which animals were
      tested. As well, LPS induced anxiogenic-like responses, including decreased time
      spent in the illuminated portion of a light-dark box, reduced open-arm entries in
      a plus-maze test, and decreased contact with a novel stimulus object in an open
      field situation. The behavioral changes were accompanied by increased plasma ACTH
      and corticosterone levels. As well, LPS induced increased turnover of
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the paraventricular
      nucleus (PVN), median eminence plus arcuate nucleus, hippocampus, as well as NE
      turnover within the locus coeruleus and DA turnover within the nucleus accumbens.
      Although these neurochemical variations were reminiscent of those elicited by
      stressors, LPS was not particularly effective in modifying DA activity within the
      prefrontal cortex or NE within the amygdala, variations readily induced by
      stressors. Whether the LPS-induced anxiogenic-like responses were secondary to
      the illness engendered by the endotoxin remains to be determined. Nevertheless,
      it ought to be considered that bacterial endotoxin challenge, and the ensuing
      cytokine changes, may contribute to emotionality and perhaps even anxiety-related
      behavioral disturbances.

PMID- 10082816
TI  - Neuroprotective electrical stimulation of cerebellar fastigial nucleus attenuates
      expression of periinfarction depolarizing waves (PIDs) and inhibits cortical
      spreading depression.
AB  - In rat, electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h
      reduces the volume of focal ischemic infarctions produced by occluding the middle
      cerebral artery (MCAO), even 10 days later. The mechanism by which this 'central
      neurogenic neuroprotection' salvages ischemic brain is not known but does not
      result from changes in cerebral perfusion. MCAO also triggers periodic
      periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory
      of salvage. These may contribute to neuronal death and promote infarct expansion.
      Conceivably, FN stimulation, which can otherwise modify cortical excitability,
      may alter the development of PIDs. We investigated in anesthetized rats whether
      FN stimulation modifies PIDs expression and, if so, the threshold for evoking
      cortical spreading depression (CSD), a process sharing characteristics with PIDs
      and an index of cortical excitability. Stimulation of FN immediately or 72 h
      before MCAO decreased infarction volumes by approximately 45% (p<0.01), increased
      PID latency >10-fold, and decreased the number of PIDs by >50% (p<0.001). In
      normal rats, stimulation of FN increased the threshold current for eliciting CSD
      by 175% and slowed its propagation velocity by 35% (p<0.01 for each) immediately,
      but not 72 h, after FN stimulation. We conclude: FN stimulation elicits long
      lasting suppression of PIDs in parallel with neuroprotection. However, PIDs
      suppression over time is unlikely to result from a major increase in cortical
      tolerance to depolarization and probably is not the principal mechanism of
      salvage.

PMID- 10082817
TI  - Phosphorylation promotes the desensitization of the opioid-induced Ca2+ increase
      in NG108-15 cells.
AB  - Using the fluorescent Ca2+ indicator fura-2, we demonstrated that, in a single
      NG108-15 cell, acute repetitive challenge with leucine-enkephalin (EK) results in
      a gradual reduction of the increase of the cytosolic Ca2+ concentration ([Ca2+]i)
      at agonist exposure times of 90 s or less; increasing the EK exposure time of
      each challenge from 30 to 90 s results in greater desensitization, with complete
      desensitization occurring at 90 s exposure. Similar results are seen with ATP. In
      opioid-desensitized cells, bradykinin can still induce a marked [Ca2+]i increase,
      while exposure of desensitized cell to 50 mM K+ restores the response EK-induced,
      suggesting a role of intracellular Ca2+ stores in the desensitization process.
      Pretreatment of cells with certain protein kinase inhibitors, including N-(2
      guanidinoethyl)-5-isoquinolinesulfonamide (HA1004) and staurosporine, prevented
      desensitization, while others, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H
      7) and {1-[N, O-bis-(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenyl
      piperazine (KN-62), had no effect. In contrast, activation of protein kinase C by
      phorbol 12-myristate 13-acetate promoted desensitization. Thus, the
      desensitization is dependent on protein phosphorylation. HA1004 alone did not
      alter EK- or bradykinin-induced inositol 1,4, 5-trisphosphate (IP3) generation;
      however, the inhibitory effect of calyculin A on EK- or bradykinin-induced IP3
      generation was reversed by HA1004. In addition, in the presence of HA1004, the
      blockade of Ca2+ influx by either verapamil or removal of extracellular Ca2+ or
      the depletion of Ca2+ pools by thapsigargin still led to desensitization,
      suggesting that phosphorylation does not alter the activity of the Ca2+
      transporters involved in Ca2+ influx and Ca2+ release. Our results imply that
      emptying of intracellular Ca2+ stores and protein phosphorylation in the
      phospholipase C signaling pathway play roles in the process of desensitization.

PMID- 10082818
TI  - Opioid neurotoxicity: fentanyl-induced exacerbation of cerebral ischemia in rats.
AB  - We tested the hypothesis that fentanyl would worsen ischemia-induced brain
      damage. In two sequential protocols forty rats were physiologically monitored and
      controlled. In protocol 1, rats were randomized (n=10/group) to 30 min of control
      (N2O plus 0.4% halothane), low dose fentanyl (loading dose [LD] 50 micrograms kg
      1, maintenance dose [MD] 2 micrograms kg-1 min-1), or high-dose fentanyl (LD 800
      micrograms kg-1, MD 32 micrograms kg-1 min-1). After 15 min of fentanyl or sham
      infusion trimethaphan 0.5 mg was given i.v. and 3 min later bilateral carotid
      artery occlusion and blood withdrawal-induced hypotension were maintained for 12
      min. At 18 h postischemia rats underwent cerebral perfusion fixation. Brain areas
      were graded from 0 (normal) to 5. In addition to analysis of specific regions,
      neuropathologic scores were also summated over all brain regions and analyzed to
      compute a summed neuropathologic score. In protocol 2, five control and five high
      dose fentanyl rats were treated identically except that post-ischemic oxygenation
      was maintained for 6 h and cerebral perfusion-fixation was performed 6 h post
      ischemia. Only the caudate/putamen was examined in protocol 2. Fentanyl worsened
      lesions in both fentanyl groups' summed neuropathologic scores (P=0.002) in
      protocol 1 and specifically, in the caudate/putamen (P<0.01) in both protocols.
      Fentanyl in both high and low doses can exacerbate incomplete forebrain ischemia
      in rats.

PMID- 10082819
TI  - Quantitative autoradiography of mu-,delta- and kappa1 opioid receptors in kappa
      opioid receptor knockout mice.
AB  - Mice deficient in the kappa-opioid receptor (KOR) gene have recently been
      developed by the technique of homologous recombination and shown to lack
      behavioural responses to the selective kappa1-receptor agonist U-50,488H. We have
      carried out quantitative autoradiography of mu-, delta- and kappa1 receptors in
      the brains of wild-type (+/+), heterozygous (+/-) and homozygous (-/-) KOR
      knockout mice to determine if there is any compensatory expression of mu- and
      delta-receptor subtypes in mutant animals. Adjacent coronal sections were cut
      from the brains of +/+, +/- and -/- mice for the determination of binding of
      [3H]CI-977, [3H]DAMGO (D-Ala2-MePhe4-Gly-ol5 enkephalin) or [3H]DELT-I (D-Ala2
      deltorphin I) to kappa1-, mu- and delta-receptors, respectively. In +/- mice
      there was a decrease in [3H]CI-977 binding of approximately 50% whilst no kappa1
      receptors could be detected in any brain region of homozygous animals confirming
      the successful disruption of the KOR gene. There were no major changes in the
      number or distribution of mu- or delta-receptors in any brain region of mutant
      mice. There were, however some non-cortical regions where a small up-regulation
      of delta-receptors was observed in contrast to an opposing down-regulation of
      delta-receptors evident in mu-knockout brains. This effect was most notable in
      the nucleus accumbens and the vertical limb of the diagonal band, and suggests
      there may be functional interactions between mu- and delta-receptors and kappa1-
      and delta-receptors in mouse brain.

PMID- 10082820
TI  - Evidence for a neural inhibitory factor which downregulates fetal-type
      acetylcholine receptor expression in skeletal muscle cell lines.
AB  - Nerve-evoked muscle depolarisation plays an important role in the downregulation
      of extrasynaptic AChRs which accompanies the increase in synaptic AChR expression
      at the neuromuscular junction during embryonic development. However, additional
      mechanisms may be involved in the AChR downregulation. This study provides
      evidence for a neurotrophic factor present in adult and embryonic chick neural
      extracts which downregulates fetal-type AChR density independently of
      depolarisation. Treatment of skeletal muscle cell lines with crude neural
      extracts decreased AChR density up to 50%, as measured by changes in 125I-alpha
      bungarotoxin binding levels. Decreases in membrane-bound AChR density were
      accompanied by a decrease in the size of the intracellular AChR pool; RT-PCR
      analysis demonstrated that extract treatment also induced a decrease in gamma
      subunit mRNA expression. These studies demonstrate that crude neural extracts
      contain a factor which may account for the activity-independent regulatory
      mechanism previously proposed to operate in concert with activity-dependent
      mechanisms to downregulate fetal-type AChR expression.

PMID- 10082821
TI  - Anatomical connections of auditory and lateral line areas of the dorsal
      telencephalon (Dm) in the osteoglossomorph teleost, Gnathonemus petersii.
AB  - Local field potentials evoked either by auditory or by mechanosensory (water
      displacement) lateral line stimuli were recorded in sensory subregions of the
      telencephalic nucleus dorsalis pars medialis (Dm) in the weakly electric fish
      Gnathonemus petersii. The neural tracer Neurobiotin was injected into these two
      physiologically defined subregions. A reciprocal connection between the two
      subregions of Dm, as well as cell bodies and terminals in other telencephalic
      regions, whose distribution was somewhat different for the two injection types,
      were found. The course of labeled fibers outside the telencephalon was similar
      after injections in both Dm regions. Fibers were seen running through the lateral
      forebrain bundle (lfb) to the ventral surface area of the brain within the
      diencephalic preglomerular region (PGv). Within a narrow streak along the ventral
      side of the brain densely arranged cell bodies were labeled. The locations of
      labeled cells within PGv were indistinguishable after tracer was injected into
      either acoustical or lateral line areas of Dm. Only after injection into the
      mechanosensory Dm region labeled cell bodies were found in the anterior
      preglomerular nucleus (PGa), in addition. When crystals of the fluorescent tracer
      DiI were inserted in the ventral part of PGv, a path of labeled fibers similar to
      that after telencephalic injections was found. Labeled terminals, but no cell
      bodies, were located both in the acoustical and in the mechanosensory regions of
      Dm as well as in several other telencephalic areas. Even though sensory regions
      in Dm that process acoustical and mechanical stimuli are segregated and unimodal,
      they both receive input from neurons of PGv. The specificity of the
      mechanosensory region of Dm might originate from the additional input from PGa
      and from other endbrain areas.

PMID- 10082822
TI  - Taurine uptake activity in the rat retina: protein kinase C-independent
      inhibition by chelerythrine.
AB  - Taurine, a regulatory amino acid of various biochemical processes in the retina,
      requires an efficient uptake system to maintain the high physiological
      concentration of taurine in the retina. Taurine uptake was characterized in both
      whole retinal preparations and in isolated rod outer segments (ROS) in terms of
      uptake kinetics and possible protein kinase C (PKC)-dependent regulation. Two
      uptake systems, a high- and a low-affinity system, were found in whole retinal
      preparations while only the high-affinity system was found in the isolated ROS.
      All the uptake systems characterized were inhibited by guanidinoethane sulfonate
      (GES), a well-known competitive inhibitor of taurine uptake. Stimulation and
      inhibition of PKC activity with phorbol myristate acetate and with staurosporine,
      respectively, produced no significant effect on taurine uptake. On the other
      hand, chelerythrine (CHT), a documented potent PKC inhibitor, was found to cause
      significant inhibition of the two taurine uptake systems, presumably through a
      PKC-independent mechanism. The data demonstrate that CHT may be a useful tool in
      studying taurine uptake in the retina and specifically in the ROS.

PMID- 10082823
TI  - Fos expression in the sleep-active cell group of the ventrolateral preoptic area
      in the diurnal murid rodent, Arvicanthis niloticus.
AB  - The ventrolateral preoptic area (VLPO) of the nocturnal laboratory rat receives
      direct input from the retina and is active during sleep; however, nothing is
      known about VLPO function in day-active (diurnal) species. In the first study, we
      used 24-h videotaping of Arvicanthis niloticus, a diurnal murid rodent, to
      estimate the distribution of sleep and wakefulness across a 12:12 light-dark
      cycle. Based on behavioral data, A. niloticus were perfused at a time when the
      animals are inactive (zeitgeber time (ZT) 20) or at a time when they are awake
      and active (ZT 23). The brains were processed for immunocytochemistry for Fos, an
      immediate early gene product used as an index of neural activity. Animals had
      more Fos-immunoreactive (Fos+) cells in the VLPO at ZT 20 than at ZT 23. The
      pattern of change in Fos expression seen in this area suggest that the VLPO
      serves the same function in A. niloticus as in rats. Eye injections of cholera
      toxin (beta subunit) were used to identify the retinal inputs to the VLPO of A.
      niloticus. In these animals, the VLPO had only very sparse retinal inputs
      compared to the rat. Together, these results raise the possibility that inputs
      from the suprachiasmatic nucleus (SCN) or the retina affect neuronal activity in
      the VLPO differently in rats and A. niloticus, thereby, contributing to
      differences in their sleep/wake patterns.

PMID- 10082824
TI  - A quantitative autoradiographic study of [3H]cAMP binding to cytosolic and
      particulate protein kinase A in post-mortem brain staged for Alzheimer's disease
      neurofibrillary changes and amyloid deposits.
AB  - The cAMP-dependent protein kinase (PKA) has been implicated in the Alzheimer's
      disease pathology of abnormal tau phosphorylation leading to neurofibrillary
      tangle (NFT) formation, as well as in amyloid precursor protein alpha-secretase
      processing. In the present study, we determined whether [3H]cAMP binding to
      cytosolic and particulate PKA showed any relationship to the extent of
      Alzheimer's disease pathology at post-mortem. Autoradiographic [3H]cAMP binding
      to cytosolic and particulate PKA was measured in sections of entorhinal
      cortex/hippocampal formation from 23 cases that had been staged for Alzheimer's
      disease-related neurofibrillary changes and amyloid deposits according to Braak
      and Braak [H. Braak, E. Braak, Neuropathological staging of Alzheimer's-related
      changes, Acta Neuropathol. 82 (1991) 239-259]. [3H]cAMP binding to cytosolic PKA
      showed statistically significant reductions in the entorhinal cortex (P<0.01,
      ANOVA) with respect to neurofibrillary changes. Post-hoc analysis with Fisher's
      PLSD test showed significant reductions of [3H]cAMP binding to cytosolic PKA at
      the isocortical stages (V and VI), compared to the non-pathological (O) (by 55%,
      P<0.01), transentorhinal (I and II) (by 58%, P<0.001) and limbic (III and IV) (by
      45%, P<0.05) stages. A significant reduction (by 25%, P<0.05) was also seen in
      the transentorhinal compared to the limbic stages. [3H]cAMP binding to cytosolic
      PKA showed no significant alterations with respect to neurofibrillary changes in
      either the subiculum, CA1-CA4 subfields of the hippocampus or the dentate gyrus.
      [3H]cAMP binding to cytosolic PKA also showed significant declines in the
      entorhinal cortex (P<0.01) and subiculum (P<0.05) with respect to staging for
      amyloid deposits. Post-hoc analysis with Fisher's PLSD test showed significant
      reductions of [3H]cAMP binding to cytosolic PKA in the entorhinal cortex at
      amyloid stage C compared to stages O (by 41%, P<0.01) and A (by 38%, P<0.01). In
      the subiculum, there were significant reductions of [3H]cAMP binding at stages C
      (by 41%, P<0.01) and B (by 40%, P<0.05), respectively, compared to stage O.
      [3H]cAMP binding to particulate PKA did not show significant relationships to
      staging for either neurofibrillary changes or amyloid deposits in either the
      entorhinal cortex or any of the hippocampal subregions. These findings suggest
      that whereas [3H]cAMP binding to cytosolic PKA in the entorhinal cortex is
      reduced with progression of neurofibrillary and amyloid pathology, other
      hippocampal regions show a preservation of cytosolic and particulate PKA even in
      late stage pathologies.

PMID- 10082825
TI  - Inhibitory and indirect excitatory effects of dopamine on sympathetic
      preganglionic neurones in the neonatal rat spinal cord in vitro.
AB  - Regions of the thoraco-lumbar spinal cord containing sympathetic preganglionic
      neurones are rich in dopamine terminals. To determine the influence of this
      innervation intracellular recordings were made from antidromically identified
      sympathetic preganglionic neurones in (400 micrometers) transverse neonatal rat
      spinal cord slices. Dopamine applied by superfusion caused a slow monophasic
      hyperpolarisation in 46% of sympathetic preganglionic neurones, a slow monophasic
      depolarisation in 28% of sympathetic preganglionic neurones and a biphasic effect
      consisting of a slow depolarisation followed by a slow hyperpolarisation or vice
      versa in 23% of sympathetic preganglionic neurones. Three percent of sympathetic
      preganglionic neurones did not respond to the application of dopamine. Low
      Ca2+/high Mg2+ Krebs solution or TTX did not change the resting membrane
      potential but abolished the slow depolarisation elicited by dopamine, indicating
      this was synaptic and did not prevent the dopamine induced hyperpolarisation. The
      dopamine induced slow hyperpolarisation was mimicked by the selective D1 agonists
      SKF 38393 or SKF 81297-C and blocked by superfusion with the D1 antagonist SCH
      23390. It was not prevented by superfusion of the slices with alpha1 or alpha2 or
      beta-adrenoceptor antagonists, whereas the inhibitory or excitatory actions of
      adrenaline were prevented by alpha1 or alpha2 antagonists, respectively. The
      dopamine induced slow depolarisation occurring in a sub-population of sympathetic
      preganglionic neurones was mimicked by quinpirole, a D2 agonist, and blocked by
      haloperidol, a D2 antagonist. Haloperidol did not block the dopamine induced
      hyperpolarisations. Dopamine also induced fast synaptic activity which was
      mimicked by a D2 agonist and blocked by haloperidol. D1 agonists did not elicit
      fast synaptic activity.

PMID- 10082826
TI  - Melatonin inhibits in vitro serotonergic phase shifts of the suprachiasmatic
      circadian clock.
AB  - The suprachiasmatic (SCN) circadian pacemaker generates 24 h rhythms of
      spontaneous neuronal activity when isolated in an acute brain slice preparation.
      The isolated pacemaker also retains its capacity to be reset, or phase-shifted by
      exogenous stimuli. For example, serotonin (5-HT) agonists advance the SCN
      pacemaker when applied during mid subjective day, while neuropeptide Y (NPY)
      agonists and melatonin advance the pacemaker when applied during late subjective
      day. Previous work has demonstrated interactions between NPY and 5-HT agonists,
      such that NPY can block 5-HTergic phase advances, while 5-HT agonists do not
      prevent NPY-induced advances. Due to a number of similarities in the actions of
      melatonin and NPY in the SCN, it seemed possible that melatonin and 5-HT might
      interact in the SCN as well. Therefore, in this study potential interactions
      between melatonin and 5-HT agonists were explored. Melatonin inhibited phase
      advances by the 5-HT agonist, (+)DPAT, and this inhibition was decreased by co
      application of tetrodotoxin. Conversely, melatonin was unable to block phase
      advances by the cyclic AMP analog, 8BA-cAMP. Finally, neither 5-HT agonists nor
      8BA-AMP were able to block melatonin-induced phase advances. These results
      demonstrate a clear interaction between melatonin and 5-HT in the SCN, and
      suggest that melatonin and NPY may play similar roles with respect to modulating
      the phase of the SCN circadian pacemaker in rats.

PMID- 10082827
TI  - Transfection and overexpression of metallothionein-I in neonatal rat primary
      astrocyte cultures and in astrocytoma cells increases their resistance to
      methylmercury-induced cytotoxicity.
AB  - Metallothionein-I (MT-I) was expressed in neonatal rat primary astrocyte cultures
      and an astrocytoma cell line by pGFAP-MT-I plasmid transfection under the control
      of the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter.
      Following transient transfection of the pGFAP-MT-I plasmid, MT-I mRNA and MT-I
      protein levels were determined by northern blot and immunoprecipitation analyses,
      respectively. The ability of cells over-expressing MT-I to withstand acute
      methylmercury (MeHg) treatment was measured by the release of preloaded
      Na251CrO4, an indicator of membrane integrity. Transfection with the pGFAP-MT-I
      plasmid led to increased mRNA (2. 5-fold in astrocytes and 7.4-fold in
      astrocytomas) and MT-I protein (2.4-fold in astrocytes and 4.0-fold in
      astrocytomas) levels compared with their respective controls. Increased
      expression of MT-I was associated with attenuated release of Na251CrO4 upon MeHg
      (5 microM) treatment. These results demonstrate that MT-I can be highly expressed
      both in primary astrocyte cultures and astrocytomas by pGFAP-MT-I plasmid
      transfection, and lend credence to the hypothesis that increased expression of MT
      I affords protection against the cytotoxic effects of MeHg. Taken together, the
      data suggest that MT offer effective cellular adaptation to MeHg cytotoxicity.

PMID- 10082828
TI  - Modulation of kainate-induced responses by pentobarbitone and GYKI-53784 in rat
      abducens motoneurons in vivo.
AB  - The modulation of kainate-induced responses by pentobarbitone and the 2,3
      benzodiazepine GYKI-53784 (LY303070), a potent non-competitive AMPA antagonist,
      was studied in vivo using both extracellular recordings of antidromic field
      potentials and intracellular recordings from abducens motoneurons in
      ketamine/diazepam-anesthetized rats. In previous studies on pentobarbitone
      anesthetized rats [M. Ouardouz, J. Durand, GYKI-52466 antagonizes glutamate
      responses but not NMDA and kainate responses in rat abducens motoneurons,
      Neurosci. Lett. 125 (1991) 5-8; M. Ouardouz, J. Durand, Involvement of AMPA
      receptors in trigeminal postsynaptic potentials recorded in rat abducens
      motoneurons in vivo, Eur. J. Neurosci. 6 (1994) 1662-1668; A. Ruiz, J. Durand,
      Blocking the trigeminal EPSPs in rat abducens motoneurons in vivo with the AMPA
      antagonists, NBQX and GYKI-53655, J. Neurophysiol. (1998) submitted], we showed
      that 2,3-benzodiazepines do not affect kainate-induced depolarizations in
      abducens motoneurons. Here, we tested whether pentobarbitone is involved in the
      pharmacological discrimination by 2,3-benzodiazepines between AMPA- and kainate
      induced responses. Kainate-induced depolarizations were reversibly depressed
      after application of either GYKI-53784 and pentobarbitone. However, kainate
      induced depolarizations were not inhibited by GYKI-53784 with pentobarbitone;
      they were even potentiated sometimes. Using extracellular recordings, we
      confirmed that in the presence of pentobarbitone, GYKI-53784 counteracts the
      effects of AMPA but not of kainate on antidromic field potentials in the abducens
      nucleus. Blockade of kainate-induced responses by GYKI-53784 was reversed with
      pentobarbitone, which appears relevant to the discrimination between AMPA- and
      kainate receptor-mediated responses in vivo. In the presence of pentobarbitone,
      kainate would depolarize motoneurons mainly via kainate receptors since kainate
      induced responses were not depressed by 2,3-benzodiazepines. This finding
      strongly favors the existence of kainate receptors in adult motoneurons but their
      role is still unknown.

PMID- 10082829
TI  - Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord.
AB  - We have investigated the effects of nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) on the intraspinal
      regeneration of anterogradely labeled axotomized ascending primary sensory fibers
      in the adult rat. These fibers were allowed to grow across a predegenerated
      peripheral nerve graft and back into the thoracic spinal cord. In control animals
      that had been infused with vehicle for two weeks into the dorsal column, 3 mm
      rostral to the nerve graft, essentially no fibers had extended from the nerve
      graft back into the spinal cord. The number of sensory fibers in the rostral end
      of the nerve graft was not significantly different between control and
      neurotrophin-infused animals. With infusion of NGF, 37+/-2% of the fibers at the
      rostral end of the graft had grown up to 0.5 mm into the dorsal column white
      matter, 30+/-2% up to 1 mm, 19+/-3% up to 2 mm and 8+/-2% up to 3 mm, i.e., the
      infusion site. With infusion of NT-3, sensory fiber outgrowth was similar to that
      seen with NGF, but with BDNF fewer fibers reached farther distances into the
      cord. Infusion of a mixture of all three neurotrophins did not increase the
      number of regenerating sensory fibers above that seen after infusion of the
      individual neurotrophins. These findings suggest that injured ascending sensory
      axons are responsive to all three neurotrophins and confirm our previous findings
      that neurotrophic factors can promote regeneration in the adult central nervous
      system.

PMID- 10082830
TI  - The site of the anti-emetic action of tachykinin NK1 receptor antagonists may
      exist in the medullary area adjacent to the semicompact part of the nucleus
      ambiguus.
AB  - NK1 receptor antagonists have been shown to act centrally and to produce a broad
      spectrum anti-emetic action. To determine precisely the site of this action, we
      microinjected GR205171, an NK1 receptor antagonist, into the left medulla
      oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm
      rostral to the obex to eliminate the emetic function of that half. Fictive
      retching induced by vagal stimulation was still observed after each of 32
      injections (0.5-5 microgram in 1-30 microliter) in the area ventrolateral to the
      solitary complex in six dogs. Retching was also observed for 30 min or more after
      all but 2 of 30 injections (0.5-1 microgram in 0.5-1 microliter) in the area
      dorsal to the retrofacial nucleus in 17 dogs. In contrast, retching disappeared
      within 5-30 min after each of 20 injections (0.5-1 microgram in 1 microliter) in
      the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15
      dogs. The threshold dose for abolition of the retching response was examined in
      seven dogs and was about 0.1 ng in 1 microliter. The maximum velocity of
      salivation occurred before the onset of retching and significantly decreased
      after its abolition. These results suggest that the site of the anti-emetic
      action of NK1 receptor antagonists may lie in a limited area adjacent to the
      scAMB, and that neurons in the site induce prodromal signs and retching in a
      sequential manner.

PMID- 10082831
TI  - Delayed induction of JunB precedes CA1 neuronal death after global ischemia in
      the gerbil.
AB  - The immediate early genes (IEGs), c-jun, junB and c-fos are expressed after
      global ischemia in the gerbil. The role of these genes remains unclear. Whilst
      moderate ischemia (7 min) causes delayed CA1 neuronal death, pre-conditioning
      with mild ischemia (2 min) neuroprotects the CA1 subfield. This differential
      response allows the specific expression patterns of IEGs to be associated with
      either delayed neuronal death, or cell survival, depending upon the insult
      severity. Using a graded insult strategy we have shown that (1) early IEG
      expression is prominent in the neuronal layers of the CA3, hilar and dentate
      regions, and (2) a delayed, secondary wave of JunB expression is localized to the
      selectively vulnerable CA1 neuronal layer after moderate ischemia. This
      expression precedes the histological and histochemical features of neuronal
      death. Delayed JunB expression was not observed in animals subject to 2 min
      ischemia. The glial fibrillary acidic protein (GFAP) promotor possesses an AP-1
      binding site, the target for IEG dimers. To examine the possible link between IEG
      expression and astrocyte activation the transcriptional activation of GFAP was
      assessed. GFAP mRNA was evident within 8 h of ischemia after both insults. The
      extent of the astrocytic reaction was dependent upon the severity of the
      ischemia. The temporospatial distribution of IEG and GFAP expression differed,
      indicating that glial activation is unlikely to be regulated by the hippocampal
      expression of IEGs. We conclude that early IEG expression is involved in
      signalling mechanisms that invoke neuroprotective effects in the dentate and CA3
      regions, and that delayed JunB expression in the CA1 subfield is associated with
      neuronal death, and may be involved in the commitment or execution phases of cell
      death. Early astrocytic responses may play a role in the mechanism of ischaemic
      tolerance.

PMID- 10082832
TI  - The processing of secretogranin II in the peripheral nervous system: release of
      secretoneurin from porcine sympathetic nerve terminals.
AB  - The distribution of secretoneurin (SN), a peptide derived from secretogranin II
      (SgII), in the coeliac ganglion, the splenic nerve and the spleen was examined by
      immunohistochemistry. In the ganglion, SN immunoreactivity (IR) was unevenly
      distributed. Positive nerve terminals densely surrounded some postganglionic
      perikarya in which also intense SN-IR was present. In the crushed splenic nerves,
      intense immunoreactivities appeared proximal (but to a less extent also distal)
      to the crush of the nerve. Analysis by cytofluorimetric scanning (CFS)
      demonstrated that SN-IR and neuropeptide Y immunoreactivity (NPY-IR) were
      predominant in the axons proximal to the crush representing anterogradely
      transported components. Using radioimmunoassay (RIA) we demonstrated that upon
      electrical stimulation (10 Hz, 1 min) of the splenic nerve, significant amounts
      of SN-IR (64.2+/-2.3 fmol) were released together with NA (4. 1x106+/-0.2 fmol)
      and NPY (330.0+/-7.2 fmol) from the isolated perfused porcine spleen. To evaluate
      the processing of SgII in sympathetic neurons, boiled tissue extracts (coeliac
      ganglia and splenic nerve) and boiled spleen perfusate (used as a suitable source
      for vesicle derived peptides) were analysed by gel filtration chromatography
      followed by SN-RIA. In all cases immunoreactivity was present solely as SN,
      indicating that SgII was fully processed to the free peptide. The evidence that
      SN is transported to the nerve terminals and is released from the porcine spleen
      upon nerve stimulation, suggests that it may modulate adrenergic
      neurotransmission and may also play a role in the neuroimmune communication.

PMID- 10082833
TI  - Neuronal degeneration in the basal ganglia and loss of pallido-subthalamic
      synapses in mice with targeted disruption of the Huntington's disease gene.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder associated
      with CAG repeat expansion within a novel gene (IT15). We have previously created
      a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homologue of the HD
      gene. Homozygotes for the Hdhex5 mutation exhibit embryolethality before
      embryonic day 8.5, while heterozygotes survive to adulthood and display increased
      motor activity and cognitive deficits. Detailed morphometric and stereological
      analyses of the basal ganglia in adult heterozygous mice were performed by light
      and electron microscopy. Morphometric analyses demonstrated a significant loss of
      neurons from both the globus pallidus (29%) and the subthalamic nucleus (51%),
      with a normal complement of neurons in the caudate-putamen and substantia nigra.
      The ultrastructural appearance of sporadic degenerating neurons in these regions
      indicated apoptosis. The highest frequency of apoptotic neurons was observed in
      the globus pallidus and subthalamic nucleus. Stereological analyses in the
      subthalamic nucleus revealed a significant decrease in the numerical density of
      symmetric synapses (43%), suggesting a relatively selective loss of inhibitory
      pallido-subthalamic afferents. Immunohistochemistry using antibodies against
      enkephalin and substance-P was unremarkable in heterozygotes, indicating a normal
      complement of enkephalin-immunoreactive striatopallidal afferents and substance-P
      immunoreactive striatopeduncular and striatonigral afferents in these animals.
      These findings show that loss of an intact huntingtin protein is associated with
      significant morphological alterations in the basal ganglia of adult mice,
      indicating an important role for this protein during development of the central
      nervous system.

PMID- 10082834
TI  - Gender effects on odor-stimulated functional magnetic resonance imaging.
AB  - On standardized tests of odor identification and odor detection, women tend to
      score better than men at nearly all age groups. We sought to determine if these
      findings would translate to differences between the sexes in the volume of
      activated brain when odors are presented to subjects as the stimulants for
      functional magnetic resonance imaging (FMRI) experiments. The activation maps of
      eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years)
      were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D.
      6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T.
      Olfactory stimuli were delivered to the patients in a passive fashion using a
      Burghart OM4-B olfactometer with a nose piece inserted into the patients'
      nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol
      alternating with hydrogen sulfide) that were selective for olfactory nerve
      stimulation in the nose. The odorants were delivered to both nostrils for 1 s
      every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient
      received room air at the same flow rate. The women's group-averaged activation
      maps showed up to eight times more activated voxels than men for specific regions
      of the brain (frontal and perisylvian regions). The left and right inferior
      frontal regions showed a statistically significant increase in activation in
      women at p<0.01. In general, more women showed activation than men. The results
      suggest that (1) FMRI activation maps in subject groups can demonstrate
      correlates to psychophysical tests of olfaction, and (2) one must control for
      gender when performing odor-stimulated FMRI experiments.

PMID- 10082835
TI  - Corticotropin-releasing hormone expression is the major target for glucocorticoid
      feedback-control at the hypothalamic level.
AB  - Glucocorticoid production is controlled via the hypothalamo-pituitary-adrenal
      (HPA) axis by a negative feedback mechanism involving the glucocorticoid receptor
      (GR). A major site of regulation is the hypothalamus, where the GR is thought to
      repress the expression of genes such as corticotropin-releasing hormone (CRH) and
      arginine-vasopressin (AVP). To define the role of the GR in this feedback loop in
      more detail, the content of CRH, AVP and neurophysin in the median eminence of
      mice carrying a targeted disruption of the GR gene was studied using
      immunohistochemistry. GR-deficient mice were found to contain five times more CRH
      in the median eminence than wild-type littermates. In contrast, no significant
      change in the content of AVP was observed in the outer layer of the median
      eminence and neurophysin was also only moderately increased. Our studies suggest
      that, at the hypothalamic level, CRH synthesis is the major target for feedback
      control by the GR and that transcriptional control of AVP and neurophysin plays
      only a supportive role in this process.

PMID- 10082836
TI  - The promnesic neurosteroid pregnenolone sulfate increases paradoxical sleep in
      rats.
AB  - The effect of systemic administration of the neurosteroid pregnenolone sulfate
      (PREG-S) on sleep-wakefulness cycle and on spatial memory performances was
      investigated in male Sprague-Dawley rats. In the first experiment, the effect of
      PREG-S administration (saline, 4.75, 47.5 mg/kg, i.p.) on 24 h EEG recording was
      evaluated. In the second experiment, spatial memory performance in a two-trial
      memory task was evaluated after post-acquisition administration of similar doses
      of PREG-S as in the first experiment. Results show that PREG-S increases
      paradoxical sleep and improves the performance on the memory task yielding
      similar dose response curves. Starting 4 h after administration of 47.5 mg/kg
      PREG-S, paradoxical sleep is increased for 10 h. The PREG-S effect on spatial
      memory lasts for at least 24 h after injection. These results suggest that an
      enhancement of paradoxical sleep may be involved in the promnesic effects of this
      neurosteroid.

PMID- 10082837
TI  - Recombinant CART peptide induces c-Fos expression in central areas involved in
      control of feeding behaviour.
AB  - We have recently shown that the hypothalamic neuropeptide CART (cocaine
      amphetamine-regulated-transcript) is a leptin dependent endogenous satiety factor
      in the rat. In the present study we confirm and extend our previous observations
      by showing that intracerebroventricular (i.c.v.) administered CART(42-89) dose
      dependently inhibits 3-h food intake in food restricted rats with a lowest
      effective dose of 0.5 microgram. CART also potently inhibits NPY-induced food
      intake in satiated rats as well as nighttime food intake in free feeding animals.
      To identify brain areas potentially involved in mediating the anorectic effects
      of CART, the temporal expression pattern of the immediate early gene c-fos was
      examined in the central nervous system by immunohistochemistry in rats receiving
      recombinant CART. Compared to vehicle, CART induced c-Fos expression in several
      hypothalamic and brainstem structures implicated in the central control of food
      intake. In the hypothalamus, high numbers of c-Fos immunoreactive (-ir) cells
      were observed in the medial parvocellular part of the paraventricular nucleus and
      in the posterior part of the dorsomedial nucleus. Lower numbers of c-Fos positive
      nuclei were found in the supraoptic and arcuate nuclei. A relatively high number
      of c-Fos-ir cells was found in the central nucleus of the amygdala. In the
      brainstem, c-Fos-positive nuclei were found in the parabrachial nucleus, and in
      the nucleus of the solitary tract. Notably both the area postrema and the dorsal
      motor nucleus of the vagus were virtually devoid of c-Fos-ir cells. The present
      experiments suggest that CART peptide exerts its inhibitory effects on appetite
      by activating hypothalamic and brainstem neurones implicated in the central
      control of feeding behaviour and metabolism.

PMID- 10082838
TI  - Distribution of CREB-binding protein immunoreactivity in the adult rat brain.
AB  - We demonstrate the expression of the co-activator CREB-binding protein (CBP) in
      the nuclei of a large number of neurons and glial structures in the rat brain and
      spinal cord. Immunoblotting of nuclear extracts revealed a single band at 265
      kDa, the size of CBP. We found that CBP immunoreactivity was localized to
      cholecystokinin mRNA-expressing neurons in the hippocampus and the thalamus,
      suggesting that CBP may be involved in long-term memory and modulation of
      cortical activity. However, CBP-labeling was not ubiquitous, and many brain
      regions, including several mesencephalic and diencephalic nuclei, showed sparse
      labeling. Further, the number of neurons displaying intense CBP-labeling varied
      across animals in some regions, e.g., the hippocampus and the amygdala. Since
      competition for limited amounts of CBP and CBP-related molecules has been shown
      to be important for the integration of intracellular signaling pathways with
      transcriptional regulation, the present results suggest that varying endogenous
      levels of CBP in post-mitotic neurons is an important parameter in neuronal
      transcriptional regulation.

PMID- 10082839
TI  - Immunohistochemical localization of S-100beta in the dental pulp of the rat
      molar.
AB  - The present study was undertaken to reveal whether S-100alpha or S-100beta or
      both are present in the nerve fibers in the rat molar tooth pulp. No
      immunoreactivity for S-100alpha was observed in the molar pulp. In the root pulp,
      thick smooth-surfaced structures accompanying the blood vessel showed S-100beta
      like immunoreactivity (-LI), and occasionally a very few thin beaded elements
      exhibited S-100beta-LI. In the coronal pulp, S-100beta-like immunoreactive (-IR)
      structures arborized repeatedly and extensively; they had a predominantly thick,
      smooth-surfaced appearance, though parts appeared thin and beaded. Numerous thin
      varicose S-100beta-IR structures ran through the odontoblast cell layer, and
      further penetrated into the predentin alongside the dentinal tubules. They could
      be traced for approximately 10-20 micrometers into the predentin from the pulp
      predentin border. Immunoelectron microscopy revealed that the Schwann cells in
      the root pulp showed S-100beta-LI, and that S-100beta-LI was present in the
      axoplasm as well as Schwann cells in the coronal pulp. The S-100beta-IR axons
      were rarely surrounded by S-100beta-IR Schwann cells. In the predentin, S-100beta
      IR nerve fibers terminated in a position close to the odontoblast processes. The
      present findings indicate that S-100beta, not S-100alpha, is present in the axon
      in the dental pulp and predentin as well as in the Schwann cells.

PMID- 10082840
TI  - Immunohistochemical analysis of cyclic AMP response element binding protein
      phosphorylation in focal cerebral ischemia in rats.
AB  - Phosphorylation of cyclic AMP response element binding protein (CREB) is one of
      the most important mechanisms controlling various gene transcriptions. In the
      present study, the phosphorylation of CREB was examined immunohistochemically at
      24 h of recirculation following 1.5 h of middle cerebral artery occlusion (MCAO)
      in rats. MCAO was induced by the intraluminal suture method. The infarct core
      revealed a significant reduction in the number of immunoreactive cells with the
      anti-phosphorylated CREB and with the anti-CREB antibody, which binds to both
      unphosphorylated and phosphorylated CREB. In contrast, the peri-infarct area
      exhibited a marked increase in the number of immunopositive cells as well as in
      the intensity of nuclear staining with each antibody, so that almost all of the
      cells expressing CREB demonstrated phosphorylation of CREB. On the other hand,
      about half of the CREB immunopositive cells reacted weakly with the anti
      phosphorylated CREB antibody in the sham group. These findings indicated that the
      expression as well as phosphorylation of CREB protein was significantly activated
      in the regions surrounding the infarct area. Since phosphorylation of CREB has
      recently been implicated in signal transductions that promote the survival and
      differentiation of neurons, the present data suggest that tissue repair
      mechanisms may be markedly activated in the peri-infarct area.

PMID- 10082841
TI  - Rat osteopontin antibody is cross-reactive to a novel myelin-associated protein
      in chick.
AB  - Osteopontin (OPN) was initially identified as glycosylated phosphoprotein in
      bones of vertebrates. Recently, OPN is reported to express in the primitive
      neuroepithelia of early chick embryonic hindbrain. We have demonstrated that rat
      OPN is immunohistochemically localized in the white matter of chick CNS. We have
      further confirmed the specificity of OPN cross-immunoreaction in myelin using
      demyelinated optic nerve induced by lysophosphatidylcholine (LPC), where the
      intensity of immunoreaction was closely related to the degree of demyelination.
      Immunoblot analyses showed that rat OPN antibody recognized a protein with
      molecular weights of approximately 47 kDa from chick CNS. Our data suggest that
      the antigen recognized by rat OPN is a previously undescribed myelin-associated
      protein in the chick CNS.

PMID- 10082842
TI  - Effect of noradrenergic inputs on the cardiovascular depressor responses to
      stimulation of central nucleus of the amygdala.
AB  - Experiments were done in chloralose anesthetized, paralyzed and artificially
      ventilated male Wistar rats to investigate the effects of microinjections of
      either norepinephrine (NE) or tyramine into the central nucleus of the amygdala
      (ACe) on the arterial pressure (AP) and heart rate (HR) responses elicited by
      glutamate (Glu) stimulation of the ACe. Microinjections of Glu into the ACe
      elicited decreases in mean AP (-23+/-3 mmHg) and HR (-11+/-3 bpm).
      Microinjections of NE or tyramine into these sites did not elicit cardiovascular
      responses. However, Glu into the ACe in the presence of NE or tyramine elicited
      depressor or bradycardic response that were significantly smaller (70-100%) in
      magnitude than to Glu alone. These data suggest that noradrenergic mechanisms in
      the ACe alter the excitability of ACe neurons involved in mediating changes in
      systemic AP and HR.

PMID- 10082843
TI  - Expression and activity of 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4
      isomerase in different regions of the avian brain.
AB  - Recently, we have demonstrated, using biochemical and immunochemical methods,
      that the quail brain possesses the cholesterol side-chain cleavage enzyme
      (cytochrome P450scc) and produces pregnenolone and its sulfate ester. To clarify
      progesterone biosynthesis in the avian brain, therefore, we examined the
      expression of messenger RNA (mRNA) encoding for the enzyme 3beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4-isomerase (3beta-HSD) and its enzymatic activity
      using the quail. RT-PCR analysis together with Southern hybridization indicated
      the expression of 3beta-HSD mRNA in the brain of sexually mature birds but with
      no clear-cut sex difference. Employing biochemical techniques combined with HPLC
      analysis, the conversion of pregnenolone to progesterone was found in brain
      slices of mature males. Progesterone biosynthesis was increased in a time
      dependent manner and completely abolished by trilostane, a specific inhibitor of
      3beta-HSD. The enzymatic activity of 3beta-HSD was greatest in the cerebrum and
      lowest in the mesencephalon. A specific RIA indicated that progesterone
      concentrations in the different brain regions closely followed the level of 3beta
      HSD activity. High levels of progesterone concentration were observed in the
      diencephalon and cerebrum with lowest values in the mesencephalon. Progesterone
      levels in the brain regions were significantly higher than those in the plasma.
      These results suggest that the avian brain possesses not only cytochrome P450scc
      but also 3beta-HSD and produces progesterone. It is also indicated that
      progesterone biosynthesis in the avian brain may be region-dependent.

PMID- 10082844
TI  - Role of NMDA glutamate receptors in regulating D2 dopamine-dependent Fos
      induction in the rat striatopallidal pathway.
AB  - Acute administration of reserpine induces Fos expression in striatopallidal
      neurons, an effect blocked by pretreatment with the D2 dopamine agonist
      quinpirole. Pretreatment with the NMDA antagonists (+)MK-801 or CPP attenuated
      reserpine-mediated striatal Fos induction whereas pretreatment with ketamine or
      the inactive isomer (-)MK-801 did not. These results support a role of NMDA
      glutamate receptors in regulating the activity of the striatopallidal pathway.

PMID- 10082845
TI  - Differential inhibition by ferrous ions of [3H]MK-801 binding to native N-methyl
      D-aspartate channel in neonatal and adult rat brains.
AB  - In vitro addition or pretreatment with >/=1 microM ferrous chloride markedly
      inhibited in a concentration-dependent manner [3H]dizocilpine (MK-801) binding to
      an open ion channel associated with the N-methyl-D-aspartate (NMDA) receptor in
      rat brain synaptic membranes. The addition of NMDA agonists invariably attenuated
      the inhibition of [3H]MK-801 binding in hippocampal synaptic membranes previously
      treated with ferrous chloride, without significantly affecting that in cerebellar
      synaptic membranes. In the absence of spermidine, ferrous chloride was more
      potent in inhibiting binding in the cerebral cortex and hippocampus in adult rats
      than in those in rats at 3 days after birth, while in the striatum [3H]MK-801
      binding was 10 times more sensitive to inhibition by added ferrous chloride in
      neonatal rats than in adult rats. Addition of spermidine significantly attenuated
      the potency of ferrous chloride to inhibit binding in the cerebral cortex of
      adult rats, with facilitation of the inhibition in newborn rats. Moreover,
      spermidine significantly reduced the inhibitory potency of ferrous chloride in
      neonatal rat striatum, without markedly affecting that in adult rat striatum.
      These results suggest that ferrous ions may interfere with opening processes of
      the native NMDA channel through molecular mechanisms peculiar to neuronal
      development in a manner associated with the polyamine recognition domain.

PMID- 10082846
TI  - Amino acid release during spreading depression in a flow-compromised cortical
      area.
AB  - The glutamate concentrations in dialysate samples obtained from microdialysis
      probe implanted in the cortex were assayed during artificially induced spreading
      depression (SD) and SD with hypoperfusion. The glutamate concentrations did not
      differ even after SD induction with hypoperfusion (all p>0.05 cf. control),
      whereas anoxic depolarization caused significantly high glutamate release.
      Prolonged SD in hypoperfused area did not expose cerebral neurons to high
      glutamate concentrations.

PMID- 10082847
TI  - Human brain alpha rhythm: nonlinear oscillation or filtered noise?
AB  - The mechanism for generation of the alpha rhythm is controversial. In the current
      study, analysis in the time and frequency domains revealed that the alpha rhythm
      recorded from the scalp overlying the human occipital cortex can be entrained to
      the second or third harmonic of low frequency light flashes. These results
      support the view that the alpha rhythm is generated by a nonlinear oscillator
      rather than a narrow-band transmission system acting as a filter.

PMID- 10082848
TI  - BDNF and NT-4, but not NT-3, promote development of inhibitory synapses in the
      absence of neuronal activity.
AB  - Development of the full complement of inhibitory synapses in cerebellar cultures
      requires the presence of neuronal activity. The neurotrophins, BDNF, NT-3 and NT
      4, were applied to cerebellar explants during activity blockade. Control numbers
      of inhibitory Purkinje cell axosomatic synapses developed in the presence of the
      TrkB receptor ligands, BDNF and NT-4, but not the TrkC receptor ligand, NT-3. The
      results suggest that BDNF and NT-4 have a role in the promotion of activity
      dependent inhibitory synaptogenesis.

PMID- 10082849
TI  - Nuclear localization of ciliary neurotrophic factor in glial cells.
AB  - In this work we studied the subcellular localization of ciliary neurotrophic
      factor (CNTF) in primary culture of rat cortical type I astrocytes and rat glioma
      C6 cells, transfected COS-7 cells and in the Xenopus oocytes. In all these
      models, morphological and biochemical evidence are provided for the nuclear
      localization of CNTF. In addition the nuclear translocation of CNTF is
      temperature-sensitive and thus strongly suggestive of a mechanism of facilitated
      transport.

PMID- 10082850
TI  - Altered expression levels of G protein subclass mRNAs in various seizure stages
      of the kindling model.
AB  - The expressions of mRNAs encoding G protein alpha subunits were analyzed in the
      cerebral cortex of amygdaloid kindled rats. A remarkable increase in Gsalpha mRNA
      were observed on the bilateral cerebral cortex at 24 h after the last generalized
      seizure and persisted 3 weeks on the unstimulated side. Gi2alpha mRNA level was
      also increased on the stimulated side at 24 h and persisted 3 weeks. These result
      suggest that dysfunction of Gs and Gi2 might relate to the basic mechanisms of
      seizure generation and the maintenance of epileptogenesis.

PMID- 10082851
TI  - Selenium, an antioxidant, protects against methamphetamine-induced dopaminergic
      neurotoxicity.
AB  - Dopaminergic changes were studied in the caudate nucleus of adult female mice
      after pre- and post-treatment with an antioxidant, selenium, 72 h after the
      multiple injections of methamphetamine (METH, 4x10 mg/kg, i.p. at 2-h interval)
      or an equivalent volume of saline. Selenium treatment prevented the depletion of
      dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) in caudate nucleus resulting from the METH treatment.
      These data suggest that METH-induced neurotoxicity is mediated by free radical
      and selenium plays a protective role against METH-induced dopaminergic
      neurotoxicity.

PMID- 10082852
TI  - Patients with temporal lobe epilepsy show an increase in brain-derived
      neurotrophic factor protein and its correlation with neuropeptide Y.
AB  - Model studies on animal seizures have proposed potential involvement of the
      neurotrophins, BDNF and NGF, in human epilepsy. However, their biological
      significance in this disease itself remains to be evaluated. Here we demonstrate
      that patients with intractable temporal lobe epilepsy show a marked increase in
      protein levels of BDNF (2.6-fold, p<0.01) but not other neurotrophins. Moreover,
      the specific BDNF increase was significantly correlated with contents of
      neuropeptide Y. Thus, these results indicate the activity-dependent expression of
      BDNF in human subjects and its potential contribution to the pathophysiology of
      human epilepsy via neuropeptide Y.

PMID- 10082853
TI  - Contribution of cholinergic and gabaergic functions to memory processes in
      BALB/cANnCrlBR mice.
AB  - Several lines of evidence indicate that glucose influences on memory depend on
      interactions between glucose, glucoregulation and hippocampal cholinergic
      function. We previously demonstrated that glucose and scopolamine differentially
      affected memory consolidation for an operant bar pressing task in two closely
      related BALB/c mouse strains. Whereas glucose normally improves memory in several
      animal strains, memory consolidation was not effected by systemic glucose
      injections in BALB/cANnCrlBR mice. Moreover, these mice were relatively
      insensitive to the normally observed amnestic effects of scopolamine. We
      therefore sought to determine whether cholinergic mechanisms in the dorsal
      hippocampus were involved in such atypical drug effects on memory processing in
      that strain of mice. In Experiment 1, we examined whether post-training
      oxotremorine would also atypically influence memory consolidation for an
      appetitively reinforced operant bar pressing task following microinjection in the
      dorsal hippocampus. In Experiment 2, we examined the effects of intrahippocampal
      GABAA drugs on memory consolidation. The non-selective muscarinic agonist,
      oxotremorine, dose-dependently impaired memory and the GABAA antagonist,
      bicuculline, improved retention in BALB/cANnCrlBR mice. It was concluded that
      GABA-mediated influences on hippocampal pyramidal output in BALB/cANnCrlBR mice
      and other strains are similar; but the amnestic effects of oxotremorine from the
      dorsal hippocampus were opposite to facilitating effects normally observed in
      other animal strains. Results are discussed relative to possible altered septo
      hippocampal cholinergic neurotransmission in BALB/cANnCrlBR mice.

PMID- 10082854
TI  - Effect of ketamine on hypoxic-ischemic brain damage in newborn rats.
AB  - The present study tests the hypothesis that ketamine, a dissociative anesthetic
      known to be a non-competitive antagonist of the NMDA receptor, will attenuate
      hypoxic-ischemic damage in neonatal rat brain. Studies were performed in 7-day
      old rat pups which were divided into four groups. Animals of the first group,
      neither ligated nor exposed to hypoxia, served as controls. The second group was
      exposed to hypoxic-ischemic conditions and sacrificed immediately afterwards.
      Animals of the third and fourth groups were treated either with saline or
      ketamine (20 mg/kg, i.p.) in four doses following hypoxia. Hypoxic-ischemic
      injury to the left cerebral hemisphere was induced by ligation of the left common
      carotid artery followed by 1 h of hypoxia with 8% oxygen. Measurements of high
      energy phosphates (ATP and phosphocreatine) and amino acids (glutamate and
      glutamine) and neuropathological evaluation of the hippocampal formation were
      used to assess the effects of hypoxia-ischemia. The combination of common carotid
      artery ligation and exposure to an hypoxic environment caused major alterations
      in the ipsilateral hemisphere. In contrast, minor alterations in amino acid
      concentrations were observed after the end of hypoxia in the contralateral
      hemisphere. These alterations were restored during the early recovery period.
      Post-treatment with ketamine was associated with partial restoration of energy
      stores and amino acid content of the left cerebral hemisphere. Limited
      attenuation of the damage to the hippocampal formation as demonstrated by a
      reduction in the number of damaged neurons was also observed. These findings
      demonstrate that systemically administered ketamine after hypoxia offers partial
      protection to the newborn rat brain against hypoxic-ischemic injury.

PMID- 10082855
TI  - Calpain inhibitor entrapped in liposome rescues ischemic neuronal damage.
AB  - Transient forebrain ischemia induces activation of calpain and proteolysis of a
      neuronal cytoskeleton, fodrin, in gerbil hippocampus. This phenomenon precedes
      delayed neuronal death in hippocampal CA1 neurons. We examined effects of a
      calpain inhibitor on delayed neuronal death after transient forebrain ischemia.
      In gerbils, a selective calpain inhibitor entrapped in liposome was given
      transvenously and 30 min later, 5-min forebrain ischemia was produced by
      occlusion of both common carotid arteries. On day 7, CA1 neuronal damage was
      examined in the hippocampal slices stained with cresyl violet. Calpain-induced
      proteolysis of fodrin was also examined by immunohistochemistry and immunoblot.
      Additionally, to assure entrapment of the inhibitor by CA1 neurons, the inhibitor
      liposome complex was labeled with FITC and given to gerbils. Fluorescence in the
      hippocampal slices was examined by confocal laser scanning microscope. Selective
      CA1 neuronal damage induced by forebrain ischemia was prevented by administration
      of the inhibitor in a dose-dependent manner. Calpain-induced proteolysis of
      fodrin was also extinguished by the calpain inhibitor in a dose-dependent manner.
      Bright fluorescence of the FITC-labeled inhibitor was observed in the CA1
      neurons. The data show an important role of calpain in the development of the
      ischemic delayed neuronal death. Calpain seems to produce neuronal damage by
      degrading neuronal cytoskeleton. Our data also show a palliative effect of the
      calpain inhibitor on the neurotoxic damage, which offers a new and potent
      treatment of transient forebrain cerebral ischemia.

PMID- 10082856
TI  - Long-term sensitization of Fos-responsivity in the rat central nervous system
      after a single stressful experience.
AB  - There is considerable evidence for a role of stressful experiences in
      psychosomatic disorders in humans, but the mechanisms leading to altered
      responsivity and the relative contributions of central and peripheral neuronal
      changes, however, are still under debate. To investigate the contribution of
      specific brain areas to sensitized responsivity, rats were exposed to a single
      brief session of inescapable footshocks (preshocked) or no shocks (control) in a
      gridcage. Two weeks later, an electrified prod was inserted in the home cage for
      15 min and the behaviour recorded. One hour later rats were perfused and brain
      sections were stained for Fos protein immunoreactivity. The number of Fos
      positive neurons was quantified in 27 brain areas. No significant difference in
      behaviour was found between the groups during the shock prod challenge. A
      significantly higher number of Fos positive neurons was found in preshocked rats
      compared to controls in the following brain areas: agranular insular cortex,
      frontal cortex, nucleus accumbens, bed nucleus of the stria terminalis,
      basolateral amygdala, CA1 area of the hippocampus, paraventricular hypothalamic
      nucleus, dorsolateral central grey, locus coeruleus, nucleus of the solitary
      tract and lateral paragigantocellular nucleus. We conclude that altered
      reactivity to stressful challenges in brain areas involved in neuroendocrine and
      autonomic control may play a role in long-term sensitization of neuroendocrine
      and autonomic responses in preshocked rats under conditions where behavioural
      sensitization is not expressed.

PMID- 10082857
TI  - Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus, the principal circadian
      pacemaker, is a paired structure with two subdivisions, a ventral core receiving
      photic input and a dorsal shell receiving non-photic input. Rhythmicity is
      thought to be generated by individual SCN neurons which are coupled to achieve
      synchrony [D.K. Welsh, D.E. Logothetis, M. Meister, S.M. Reppert, Individual
      neurons dissociated from rat suprachiasmatic nucleus express independently phased
      circadian firing patterns, Neuron, 14 (1995) 697-706]. Normally, the core and
      shell, and the nuclei on each side, act in unison to transmit rhythmicity to
      effector systems. It is not known how coupling between neurons in the two
      subdivisions, and between the two SCNs, takes place. In the present study, we
      analyze the intrinsic, commissural, and efferent projections of the SCN using the
      swine herpesvirus (pseudorabies virus, PRV) as a tool for transynaptic analysis
      of circuits and small iontophoretic injections of the conventional tracer
      horseradish peroxidase (HRP) conjugated to fluorescein. We find that the core and
      shell each project through commissural efferents to homologous contralateral
      areas. The core projects densely to shell but we find little reciprocal
      innervation. The two subdivisions project to different hypothalamic areas, with
      the core projecting to the lateral subparaventricular zone and shell to the
      dorsomedial hypothalamic nucleus and medial subparaventricular zone. These data
      are the first demonstration that connections within the SCN, and from the SCN to
      effector regions, are topographically organized and lend insight into the flow of
      information through and out of the pacemaker.

PMID- 10082858
TI  - Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and
      splice variant mRNA expression in the rat cerebral cortex.
AB  - Chronic ethanol exposure and subsequent withdrawal are known to change NMDA
      receptor activity. This study examined the effects of chronic ethanol
      administration and withdrawal on the expression of several NMDA receptor subunit
      and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was
      induced by ethanol vapour exposure. To delineate between seizure-induced changes
      in expression during withdrawal and those due to withdrawal per se, another group
      of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg,
      i.p.). RNA samples from the cortices of chronically treated and withdrawing
      animals were compared to those from pair-fed controls. Changes in NMDA receptor
      mRNA expression were determined using ribonuclease protection assays targetting
      the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively
      spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants
      generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA
      incorporating the 5' insert vs. that lacking it was decreased during ethanol
      exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated
      during exposure, but returned to control levels 18 h after withdrawal. Levels of
      NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups
      did not alter compared with the pair-fed control group. No changes in the level
      of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These
      data support the hypothesis that changes in NMDA receptor subunit composition may
      underlie a neuronal adaptation to the chronic ethanol-inhibition and may
      therefore be important in the precipitation of withdrawal hyperactivity.

PMID- 10082859
TI  - Benzodiazepine withdrawal facilitates the subsequent onset of escape failures and
      anhedonia: influence of different antidepressant drugs.
AB  - The effect of benzodiazepine (BDZ) withdrawal on escape acquisition and on the
      behavioral response to two different reinforcing stimuli was investigated. In
      addition, the influence of antidepressant drugs (AD) differing in their mechanism
      of action on these behavioral outputs was also evaluated. Rats subjected to
      withdrawal from a chronic treatment with diazepam (DZM; 2 mg/kg per day, i.p.)
      during 21 days were subsequently exposed to a brief inescapable shock session
      (IS) and 48 h later to an active avoidance test. Only withdrawn animals exposed
      to the IS exhibited enhanced escape failures. In an additional experiment,
      withdrawn rats were repeatedly administered with vehicle (VEH), desipramine (DMI;
      5 mg/kg, i.p.), fluoxetine (FLU; 5 mg/kg, i.p.) or phenelzine (PHEN; 5 mg/kg,
      i.p.) and subsequently exposed to IS and to active avoidance task. A significant
      reversal of escape deficit was only observed following DMI and PHEN but not after
      FLU. Furthermore, withdrawn rats showed a reduced preference for a sexually
      relevant olfactory cue, this reduced sensitivity was only normalized following
      DMI but not after the administration of FLU or PHEN. Finally, rats exposed to
      abrupt cessation of chronic BDZ administration did not exhibit preference for a
      context previously associated with amphetamine (AMP) under the conditioned place
      preference (CPP) procedure. All these findings are indicative that BDZ withdrawal
      facilitates the subsequent occurrence of behavioral changes-escape failures and
      reduced behavioral response to rewarding stimuli-suggested to parallel important
      symptoms of human depression. In addition, DMI seems to be much more effective in
      restoring such behavioral abnormalities as compared to a MAO inhibitor and to a
      inhibitor of 5-HT uptake.

PMID- 10082860
TI  - Effects of morphine on the distribution of Fos protein in the trigeminal
      subnucleus caudalis neurons during experimental tooth movement of the rat molar.
AB  - The present study was undertaken to disclose temporal changes in the distribution
      of Fos-like immunoreactive (-IR) neurons in the trigeminal subnucleus caudalis
      (SpVc), one of the important relay nuclei for processing the nociceptive
      information from the oro-facial regions, following induction of experimental
      tooth movement in rat upper molars. Furthermore, the effect of morphine and
      naloxone on the levels of Fos-IR neurons in the SpVc was examined. The
      experimental tooth movement was induced by insertion of an elastic rubber between
      the first and second upper molars. In normal animals, Fos-IR neurons were rarely
      observed in the SpVc. Immediately after insertion of the elastic band, the
      distribution of Fos-IR neurons was comparable to that observed in normal animals.
      The number of Fos-IR neurons increased significantly from 1 to 4 h following the
      induction of experimental tooth movement, reaching a maximum at 2 h, and then
      decreasing gradually. Most of the neurons were localized in the dorsomedial
      portion of the superficial layers of the ipsilateral SpVc near the obex, but a
      few were observed at the ventral portion of the SpVc. The neurons at the
      superficial layers and ventral portion of the contralateral SpVc also showed Fos
      like immunoreactivity, but their numbers were significantly smaller than those on
      the ipsilateral side. Pretreatment with morphine (3 and 10 mg/kg, i.p.)
      significantly reduced the induction of Fos-IR neurons at the superficial layers
      of the ipsilateral SpVc in a dose-dependent manner, and its effect was
      antagonized by the subsequent treatment of naloxone (2 mg/kg, i.p.). Naloxone
      pretreatment enhanced the expression of Fos-IR neurons on the ipsilateral SpVc.
      The present results of a reduction of Fos-IR neurons by morphine pretreatment
      suggest that the induction of Fos-IR neurons may be due to the noxious
      stimulation caused by induction of experimental tooth movement.

PMID- 10082861
TI  - Immunoelectron microscopy of AMPA receptor subunits reveals three types of
      putative glutamatergic synapse in the rat vestibular end organs.
AB  - To characterize the synapses between hair cells and afferent nerve endings in the
      rat vestibular end organs, the ultrastructural localization of AMPA receptor
      subunits (GluR1-4) was examined by postembedding immunogold cytochemistry.
      Immunoreactivities for GluR2/3 and GluR4 were associated with the synapses
      between type I hair cells and the surrounding chaliceal nerve endings and with
      the bouton type nerve endings contacting type II hair cells. There was no
      detectable immunoreactivity for GluR1. A third type of immunoreactive synapse was
      found between the outer face of chalices and type II hair cells. While the linear
      densities of gold particles (particles per micrometer postsynaptic
      specialization) of bouton type endings and chaliceal nerve endings were the same,
      the former type of ending showed larger postsynaptic specializations and, hence,
      a higher number of receptor molecules. These data indicate that there are three
      types of putative glutamatergic synapse in the vestibular end organ.

PMID- 10082862
TI  - Evaluation of glycine site antagonists of the NMDA receptor in global cerebral
      ischaemia.
AB  - In the present studies we have investigated the effects of a range of glycine
      site antagonists of the N-methyl-d-aspartate (NMDA) receptor in the gerbil model
      of global cerebral ischaemia. The compounds tested were (+)-3-amino-1-hydroxy-2
      pyrrolidone (HA 966, 15 mg/kg), 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)
      quinolinone) (L-701,324, 40 mg/kg), 7-chloro-3-(cyclopropylcarbonyl)-4-hydroxy
      2(1H)-quinolinone) (L-701, 252, 50 mg/kg), (3-(3-hydroxyphenyl)prop-2-ynyl 7
      chloro-4 hydroxy-2(1H)-quinolone-3-carboxylate) (L-701,273, 50 mg/kg), 5-nitro
      6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 25 mg/kg) and [(E)
      3[(phenylcarbamoyl) ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV
      150526A, 40 mg/kg). All compounds were administered via the i.p. route 30 min
      before and again at 2 h 30 min after 5 min bilateral carotid artery occlusion
      (BCAO) in the gerbil. For comparison we also evaluated a non-competitive NMDA
      antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10
      imine (MK-801, 2 mg/kg) and an alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) antagonist, (3S,4aR, 6R, 8aR)-6-[2-(1(2)H-tetrazole-5
      yl)]decahydroisoquinoline-3-car boxylic acid (LY293558, 20 mg/kg). In the present
      studies L-701,252, L-701, 324 and L-701,273 provided a small degree of
      neuroprotection. ACEA 1021, GV 150526A and HA 966 failed to provide any
      neuroprotection, while MK-801 provided significant (20%) protection. In contrast
      LY293558 provided good (55%) neuroprotection. These results indicate that glycine
      site antagonists and competitive NMDA antagonists provide a small degree of
      neuroprotection in global cerebral ischaemia. In contrast, AMPA receptor
      antagonists provide more robust neuroprotection in global cerebral ischaemia.

PMID- 10082863
TI  - Subunit dependent modulation of GABAA receptor function by neuroactive steroids.
AB  - Neurosteroids are potent, endogenous modulators of GABAA receptor function in the
      central nervous system. The endogenous progesterone metabolite allopregnanolone
      (ALP) and the synthetic steroid compound alphaxalone (AFX) have been shown to
      both directly activate and potentiate GABAA receptor-activated membrane current
      (IGABA). The role of different alpha and gamma subunit subtypes in modulation of
      IGABA by ALP and AFX was investigated using recombinant GABAA receptor isoforms
      expressed in Xenopus oocytes. Changing or removal of the alpha subunit subtype
      altered the efficacy of both ALP and AFX
      (alpha2beta1gamma2L>alpha1beta1gamma2L>>beta1gamma2L) to potentiate IGABA, but
      did not alter the potency of the neuroactive steroids at these receptor isoforms.
      The efficacy of ALP to enhance IGABA was also dependent on the gamma subunit
      subtype (alpha1beta1gamma3>alpha1beta1gamma2L = alpha1beta1gamma1). AFX also had
      higher efficacy in the alpha1beta1gamma3 receptor isoform compared to
      alpha1beta1gamma1. In contrast to ALP, the potency of AFX was greater in the
      alpha1beta1gamma3 and alpha1beta1gamma1 receptor isoforms compared to
      alpha1beta1gamma2L. This study provides evidence that the alpha subunit subtype
      determines the efficacy, but not the potency, of these neuroactive steroids to
      potentiate IGABA. The gamma3 subunit subtype increases the maximal efficacy of
      neuroactive steroids compared to other gamma subunit subtypes. These results
      suggest that the heteromeric assembly of different GABAA receptor isoforms
      containing different subunit subtypes results in multiple steroid recognition
      sites on GABAA receptors that in turn produce distinctly different modulatory
      interactions between neuroactive steroids acting at the GABAA receptor.

PMID- 10082864
TI  - Seasonal plasticity of neuromuscular junctions in adult male Siberian hamsters
      (Phodopus sungorus).
AB  - Transfer of adult Siberian hamsters, Phodopus sungorus, from long day (16 h light
      and 8 h dark; 16L:8D) to short day (8L:16D) photoperiods induces an involution of
      the gonads and a cessation of reproductive behavior 8-10 weeks later. The
      motoneurons of the spinal nucleus of the bulbocavernosus and their target
      muscles, the bulbocavernosus and the levator ani, are sexually dimorphic and are
      necessary for successful reproduction by male mammals. We demonstrate that after
      transfer of adult male Siberian hamsters to short photoperiods, the
      bulbocavernosus motoneurons, their target muscles and neuromuscular junctions are
      all significantly smaller than those of males that remain under long day
      conditions. Photoperiod also affected the number of active zones within each
      neuromuscular junction, an apparent remodeling of these synapses. Thus, this
      neuromuscular system of adult Siberian hamsters demonstrates considerable
      seasonal plasticity in response to changes in photoperiod.

PMID- 10082865
TI  - The response of muscle spindle primary afferents to simultaneously presented
      sinusoidal and ramp-and-hold stretches.
AB  - Fifteen primary (Ia) muscle spindle afferents from the tibial anterior muscle of
      the cat were subjected to a ramp-and-hold stretch (stretch rate 10 mm/s, stretch
      amplitude 8.5 or 7 mm) of the muscle, upon which was superimposed a sinusoidal
      stretch (10 Hz) of five different amplitudes (50, 100, 500, 1000 and 2000 microm
      peak to peak). The response of the Ia afferents to the sinusoidally overlaid ramp
      and-hold stretch was subjected to computer analysis, by means of which the
      response to the superimposed sinusoids and the response to the underlying ramp
      and-hold stretch were each obtained separately. Four basic discharge frequencies
      were determined from the response to the underlying ramp-and-hold stretch
      (obtained after elimination of the response to the concomitant sinusoidal
      stretch). The evaluation yielded the result that the concomitant sinusoidal
      stretch affected the response to the underlying ramp-and-hold stretch: the level
      of discharge of the Ia afferent was significantly increased and the dynamic and
      static indices were significantly diminished. These two effects intensified with
      increasing amplitude of the concomitant sinusoids. From among the oscillatory
      responses of the Ia afferent to the concomitant sinusoidal stretch (obtained
      after elimination of the response to the underlying ramp-and-hold stretch) the
      amplitudes of four selected responses were determined. These four oscillatory
      responses occurred during four time spans during which the four basic discharge
      frequencies were read. Evaluation showed that the response to the underlying ramp
      and-hold stretch affected the modulation depth of the oscillatory responses,
      which decreased during the ramp and increased again during the plateau. The
      absolute amount of the change was independent of the amplitude of the sinusoids.
      The effect of the sinusoids on the response to the underlying ramp-and-hold
      stretch and that of the underlying ramp-and-hold stretch on the response to the
      sinusoidal stretches are interpreted in terms of ion currents occurring at the Ia
      sensory terminals. It is assumed that the probability of the stretch activated
      (SA) channels opening is increased by a stretching of the sensory terminals. A
      depolarizing Na+ and Ca++ inward current due to the activation of the SA channels
      in its turn activates a Ca++-activated and/or a potential-dependent K+ outward
      current which has a repolarizing effect. Ideas are put forward in the discussion
      as to how the inward and outward currents that are sinusoid-related and those
      that are ramp-and-hold-stretch related interact.

PMID- 10082866
TI  - Transmission of afferent information from urinary bladder, urethra and perineum
      to periaqueductal gray of cat.
AB  - The micturition reflex pathway is a supraspinal pathway. Anatomical tracing
      evidence is compatible with an involvement of the periaqueductal gray (PAG) in
      the ascending limb of this reflex. We tested the involvement of the PAG in
      receiving urinary tract- or perineum-related information and attempted to
      characterize this ascending path in terms of what type of information is being
      conveyed. Electrical stimulation of the pelvic nerves, which carry afferent
      information from the urinary bladder, evoked maximum field potentials in the
      caudal third of the PAG, primarily in the dorsal part of the lateral PAG and in
      the ventrolateral PAG. Since the regions activated by pelvic nerve stimulation
      differed from those activated by stimulation of the sensory pudendal or
      superficial perineal nerves, it is possible that specific pathways for different
      nerve inputs to the PAG exist. Sacral spinal cord neurons ascending to the PAG
      were identified by antidromic activation and then tested for inputs from pelvic,
      sensory pudendal or superficial perineal nerves. Of 18 units identified, only
      five received inputs from any of the peripheral nerves tested and only two
      projecting neurons received a pelvic nerve input. Thus the PAG may receive inputs
      from bladder and perineum, but the small proportion of cells with direct
      projections to the PAG receiving inputs from our test nerves implies that the
      major part of this pathway is not directly related to lower urinary tract
      function.

PMID- 10082867
TI  - Selective impairment of fast anterograde axonal transport in the peripheral
      nerves of asymptomatic transgenic mice with a G93A mutant SOD1 gene.
AB  - Transgenic mice that express a mutant Cu/Zn superoxide dismutase (SOD1) gene have
      been provided a valuable model for human amyotrophic lateral sclerosis (ALS). We
      studied a possible impairment of fast axonal transport in transgenic mice
      carrying a Gly93-->Ala (G93A) mutant SOD1 gene found in human familial ALS
      (FALS). Left sciatic nerve was ligated for 6 h in transgenic (Tg) and age-matched
      wild-type (WT) mice. Immunohistochemical analyses were performed for
      accumulations of kinesin and cytoplasmic dynein on both sides of the ligation
      site. Clinical function and histology in the spinal cords, sciatic nerves and
      gastrocnemius muscles were also assessed. The mice were examined at an early
      asymptomatic stage (aged 19 weeks) and a late stage (30 weeks) just before the
      development of the symptoms. WT mice showed an apparent increase in
      immunoreactivities for kinesin and cytoplasmic dynein at proximal and distal of
      the ligation, respectively. In contrast, the young Tg mice showed a selective
      decrease of kinesin accumulation in the proximal of the ligation. The mice were
      asymptomatic with a mild histological change only in muscles. The old Tg mice
      showed a marked reduction of the immunoreactivity for kinesin and cytoplasmic
      dynein on both sides of the ligation. They had a significant loss of spinal motor
      neurons, relatively small myelinated fiber densities of sciatic nerves, and
      severe muscular changes. These results provide direct evidence that the SOD1
      mutation leads to impaired fast axonal transport, particularly in the anterograde
      direction at an early, asymptomatic stage preceding loss of spinal motor neurons
      and peripheral axons. This impairment may contribute to subsequent selective
      motor neuron death in the present model implicated for human FALS.

PMID- 10082868
TI  - Focal cerebral ischaemia induces a decrease in activity and a shift in ouabain
      affinity of Na+, K+-ATPase isoforms without modifications in mRNA and protein
      expression.
AB  - In a mouse model of focal cerebral ischaemia, we observed after 1 h of ischaemia,
      that the total Na+, K+-ATPase activity was decreased by 39.4%, and then did not
      vary significantly up to 6 h post-occlusion. In the sham group, the dose-response
      curves for ouabain disclosed three inhibitory sites of low (LA), high (HA) and
      very high (VHA) affinity. In ischaemic animals, we detected the presence of only
      two inhibitory sites for ouabain. After 1 h of permanent occlusion, the first
      site exhibited a low affinity while the second site presented an affinity
      intermediate between those of HA and VHA sites, which evolved after 3 h and 6 h
      of occlusion towards that of the VHA site. The presence of only two ouabain sites
      for Na+, K+-ATPase after ischaemia could result from a change in ouabain affinity
      of both HA and VHA sites (alpha2 and alpha3 isoforms, respectively) to form a
      unique component. Irrespective of the duration of ischaemia, the smaller activity
      of this second site accounted entirely for the loss in total activity.
      Surprisingly, no modifications in protein and mRNA expression of any alpha or
      beta isoforms of the enzyme were observed, thus suggesting that ischaemia could
      induce intrinsic modifications of the Na+, K+-ATPase.

PMID- 10082869
TI  - P-Glycoprotein on astrocyte foot processes of unfixed isolated human brain
      capillaries.
AB  - Sites of immunoreactive P-glycoprotein associated with human brain
      microvasculature were identified by labeling of unfixed isolated human brain
      capillaries, allowing visualization of the three-dimensional capillary structure
      by confocal microscopy. Capillaries isolated from human autopsy brain were dual
      labeled with the MRK16 mouse monoclonal antibody (against human P-glycoprotein)
      and rabbit polyclonal antisera against the human brain microvascular glucose
      transporter (GLUT1), or glial fibrillary acidic protein (GFAP) on astrocyte foot
      processes. MRK16 and GLUT1 dual-labeling showed no signal overlap, identical to
      the staining pattern observed for dual-labeling with anti-GFAP and anti-GLUT1
      antibodies: both GFAP and MRK16 labeling were discrete, discontinuous, and not co
      localized with continuous GLUT1 labeling of capillary endothelium. In contrast,
      complete overlap of MRK16 and GFAP labeling demonstrated P-glycoprotein
      localization on astrocyte foot process remnants at the abluminal face of the
      brain microvasculature.

PMID- 10082870
TI  - Modulation of hypoxic depressions of ventilatory activity in the newborn piglet
      by mesencephalic mechanisms.
AB  - In neonates, ventilatory responses to hypoxia are 'biphasic,' with an
      augmentation followed by a decline. The hypoxia-induced augmentations in
      ventilation are attenuated and the depressions are accentuated following
      denervation of the peripheral chemoreceptors. Piglets that were decerebrated at a
      rostral mesencephalic level exhibited these hypoxia-induced depressions. These
      depressions were lessened following transection through the caudal mesencephalon.
      Mesencephalic mechanisms play a fundamental role in the brainstem regulation of
      ventilatory responses to hypoxia.

PMID- 10082871
TI  - High glucose-6-phosphate dehydrogenase activity contributes to the structural
      plasticity of periglomerular cells in the olfactory bulb of adult rats.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) activity, assayed
      spectrophotometrically, was found to be higher in the olfactory bulb (OB) than in
      other brain areas of adult rats [P. Ninfali, G. Aluigi, W. Balduini, A. Pompella,
      Glucose-6-phosphate dehydrogenase is higher in the olfactory bulb than into other
      brain areas, Brain Res. 744 (1997) 138-142]. Histochemical demonstration of G6PD
      activity in cryostat sections of OB, analyzed with optical microscopy, revealed a
      marked and well defined line of formazan deposition in the internal part of the
      glomerular layer (Glm), indicating that G6PD was much higher in cells distributed
      along the glomeruli. Electron microscope analysis showed that G6PD activity was
      mainly concentrated in cytoplasm and dendrites of periglomerular cells, the
      interneurons which span glomeruli and connect olfactory nerves with mitral/tufted
      cells. Since G6PD regulates the flux through the hexose monophosphate shunt (HMS)
      pathway, which provides NADPH for reductive biosynthesis and pentose phosphates
      for nucleic acid formation, it can be concluded that high G6PD activity in
      periglomerular neurons is functional to their differentiating capability. This
      result is consistent with the occurrence of structural plasticity events in the
      OB of adult rats.

PMID- 10082872
TI  - Naloxone reduces the amplitude of IPSPs evoked in lumbar motoneurons by reticular
      stimulation during carbachol-induced motor inhibition.
AB  - During active sleep or carbachol-induced motor inhibition, electrical stimulation
      of the medullary nucleus reticularis gigantocellularis (NRGc) evoked large
      amplitude, glycinergic inhibitory postsynaptic potentials (IPSPs) in cat
      motoneurons. The present study was directed to determine whether these IPSPs,
      that are specific to the state of active sleep, are modulated by opioid peptides.
      Accordingly, intracellular recordings were obtained from lumbar motoneurons of
      acute decerebrate cats during carbachol-induced motor inhibition while an opiate
      receptor antagonist, naloxone, was microiontophoretically released next to the
      recorded cells. Naloxone reversibly reduced by 26% the mean amplitude of NRGc
      evoked IPSPs (1.9+/-0.2 mV (S.E.M.) vs. 1.4+/-0.2 mV; n=11, control and naloxone,
      respectively, p<0.05), but had no effect on the other waveform parameters of
      these IPSPs (e.g., latency-to-onset, latency-to-peak, duration, etc.). The mean
      resting membrane potential, input resistance and membrane time constant of
      motoneurons following naloxone ejection were not statistically different from
      those of the control. These data indicate that opioid peptides have a modulatory
      effect on NRGc-evoked IPSPs during carbachol-induced motor inhibition. We
      therefore suggest that endogenous opioid peptides may act as neuromodulators to
      regulate inhibitory glycinergic synaptic transmission at motoneurons during
      active sleep.

PMID- 10082873
TI  - Reverse transport of glutamate during depolarization in immature hippocampal
      slices.
AB  - We studied the source of extracellular glutamate released by hippocampal slices
      obtained from P14 or adult rats, during 50 mM K+ depolarization by using two
      potent inhibitors of Na+-dependent glutamate transport: l-trans-pyrrolidine-2,4
      dicarboxylate (PDC), which is a relatively non-selective inhibitor of various
      glutamate transporter subtypes and dihydrokainic acid (DHK), a specific inhibitor
      of the glial transporter, GLT-1. Most depolarization-induced glutamate release
      was Ca2+-dependent in adults, while in P14 slices most glutamate release was Ca2+
      independent. PDC decreased depolarization-induced glutamate release in P14 slices
      but not in adults. DHK increased glutamate release in adults but not in P14
      slices. These data suggest that most depolarization-induced glutamate release in
      immature hippocampal slices is due to reversal of transport through a PDC
      sensitive Na+-dependent glutamate transporter, presumably acting on presynaptic
      or cytoplasmic neuronal pools, and is not due to exocytosis from vesicular pools.

PMID- 10082874
TI  - Blockade of glutamate reuptake in the rat nucleus accumbens increases locomotor
      activity.
AB  - The effect on locomotor activity of blocking glutamate reuptake in the nucleus
      accumbens (NAcc) was investigated in the rat. Bilateral intracranial
      microinjections into the NAcc of the selective glutamate reuptake blocker, l
      trans-pyrrolidine-2,4-dicarboxylic acid (PDC), were made in the freely moving rat
      and locomotor activity subsequently measured for 2 h. Different groups of rats
      injected with one of three doses of PDC (0.5, 5 or 10 nmole/0.5 microl/side)
      showed significant dose-dependent increases in both horizontal and vertical
      locomotor activity relative to control rats that received injections of the
      saline vehicle. These findings indicate that glutamate in the NAcc plays an
      important role in the production of locomotor behaviors.

PMID- 10082875
TI  - Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on
      cultured mesencephalic neurons.
AB  - Pretreatments with TNF-alpha and lower concentrations of C2-ceramide protected
      cultured mesencephalic neurons from excitotoxicity in a dose-dependent manner.
      These protective effects are reduced by cotreatment with N,N-dimethylsphingosine
      (DMS), an inhibitor of sphingosine kinase. Since the pretreatment with
      sphingosine-1-phosphate (SPP) showed a neuroprotective effect, our data suggest
      that protective effects of TNF and C2-ceramide could be attributable to their
      further metabolism to SPP.

PMID- 10082876
TI  - Testis-brain RNA-binding protein (Translin) is primarily expressed in neurons of
      the mouse brain.
AB  - The subcellular location(s) of the DNA- and RNA-binding protein, Testis-Brain RNA
      Binding Protein (TB-RBP)/Translin in mouse brain has been determined in paraffin
      sections by immunocytochemistry with an affinity purified antibody to mouse
      recombinant TB-RBP. Nuclear staining was frequently seen in neurons throughout
      the brain, but no TB-RBP/Translin was detected in many of the neurons in
      superficial layers of the cerebral cortex and in some cells of the cerebellum.
      Cytoplasmic staining extending into the dendrites was seen in large neurons such
      as pyramidal neurons in Layer 5 of the cortex and magnocellular neurons of the
      hypothalamus or the brainstem raphe.

PMID- 10082877
TI  - The antinociception produced by microinjection of a cholinergic agonist in the
      ventromedial medulla is mediated by noradrenergic neurons in the A7 catecholamine
      cell group.
AB  - Activation of neurons in the ventromedial medulla by electrical stimulation or by
      microinjection of opioid or cholinergic agonists produces antinociception that is
      mediated in part by spinally-projecting noradrenergic neurons. Several lines of
      evidence indicate that these noradrenergic neurons are located in the pontine A7
      catecholamine cell group. For example, anatomical studies have demonstrated that
      neurons in the ventromedial medulla project to the noradrenergic neurons in the
      A7 catecholamine cell group that provide the major noradrenergic innervation of
      the spinal cord dorsal horn. In addition, electrical and chemical stimulation of
      A7 neurons produces antinociception that can be reduced by intrathecal injection
      of alpha2-adrenoceptor antagonists. The present studies provide more direct
      evidence that activation of neurons in the ventromedial medulla produces
      antinociception by activating noradrenergic neurons in the A7 cell group. Neurons
      in the ventromedial medulla were stimulated by microinjecting the cholinergic
      agonist carbachol (5 microg) into sites in the nucleus raphe magnus or the
      nucleus gigantocellularis pars alpha of pentobarbital anesthetized Sprague-Dawley
      rats. In some experiments, the local anesthetic tetracaine (10 microg) was then
      microinjected near the A7 cell group to inactivate the spinally-projecting
      noradrenergic neurons. In other experiments, cobalt chloride (100 mM) was
      microinjected near the A7 cell group to block synaptic activation of spinally
      projecting noradrenergic neurons. Microinjection of carbachol into sites in the
      ventromedial medulla produced antinociception, assessed using the tail flick
      test, that lasted more than 60 min. However, the effects of carbachol were
      attenuated by microinjection of either tetracaine or cobalt into sites near the
      A7 cell group neurons identified by tyrosine hydroxylase-immunoreactivity.
      Similar injections of tetracaine or cobalt more than 500 microm from the A7
      neurons did not alter the antinociceptive effect of carbachol. These results
      support the conclusion that the antinociception produced by activating neurons in
      the ventromedial medulla is mediated in part by the subsequent activation of
      spinally-projecting noradrenergic neurons in the A7 cell group.

PMID- 10082878
TI  - Alterations of GABAA receptor subunit mRNA levels associated with increases in
      punished responding induced by acute alprazolam administration: an in situ
      hybridization study.
AB  - Changes in the mRNA encoding alpha1, alpha2, beta2 and gamma2 subunits of the
      GABAA receptor associated with the anxiolytic effects of alprazolam were measured
      in 20 brain regions using in situ hybridization techniques. Compared to non
      punished controls, punishment decreased alpha1 mRNA levels in two nuclei of the
      amygdala, the cerebral cortex, and the mediodorsal thalamic nucleus and decreased
      alpha2 mRNA levels in the hippocampus. Punishment increased beta2 mRNA levels in
      ventroposterior thalamic nucleus and gamma2 mRNA levels in the CA2 area of the
      hippocampus. All of these effects were reversed when alprazolam increased
      punished responding, while alprazolam alone had no effect on either non-punished
      responding or GABAA receptor subunit regulation in these brain regions. Some
      brain regions that were unaffected by punishment were altered by alprazolam plus
      punishment. These results demonstrate that punishment and alprazolam can produce
      reciprocal changes in the mRNA levels for some subunits of the GABAA receptor.
      These changes may alter GABAergic synaptic inhibition by altering the density of
      GABAA receptors or their efficacy to bind drugs. They suggest that the underlying
      mechanisms by which drugs affect behavior can depend upon the conditions under
      which behavior is assessed.

PMID- 10082879
TI  - Pre- and postsynaptic distribution of cannabinoid and mu opioid receptors in rat
      spinal cord.
AB  - In vitro receptor binding and quantitative autoradiography were used to assess
      the pre- and postsynaptic distribution of cannabinoid receptors in the cervical
      dorsal horn of the rat spinal cord. An extensive unilateral dorsal rhizotomy was
      performed across seven or eight successive spinal segments from C3 to T1 or T2.
      The densities of cannabinoid and mu opioid receptors in the central (C6) spinal
      segment were assessed 2, 4, 8, and 16 days post rhizotomy and compared with those
      of untreated rats. Rhizotomy induced approximately a 50% ipsilateral loss in the
      [3H]CP55,940 binding to spinal cannabinoid receptors that was maximal at 8 days
      post-rhizotomy. By comparison, the binding of [3H][d-Ala2-MePhe4, Gly
      ol5]enkephalin (DAMGO) to mu receptors was depleted approximately 60% in near
      adjacent sections. By contrast, changes in [3H]CP55,940 binding contralateral to
      the deafferentation were largely absent at all post-lesion delays. These data
      suggest that under conditions in which a spinal segment is completely
      deafferented, approximately 50% of cannabinoid receptors in the cervical (C6)
      dorsal horn reside presynaptically on central terminals of primary afferents. The
      present data provide anatomical evidence for presynaptic as well as postsynaptic
      localization of cannabinoid receptors in the spinal dorsal horn.

PMID- 10082880
TI  - Transmission routes of HIV-1 gp120 from brain to lymphoid tissues.
AB  - The blood-brain barrier (BBB) restricts the entry of antiviral agents into the
      CNS thereby facilitating the creation of a reservoir of HIV that could
      potentially reinfect peripheral tissues. We characterized the efflux from brain
      of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after
      intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I
      gp120 from brain was 12.6 min, which was faster than could be explained by the
      reabsorption of cerebrospinal fluid into blood but could not be explained by a
      saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and
      was sequestered by spleen and the cervical nodes, demonstrating a potential for
      virus within the CNS to reinfect peripheral tissues. However, the amount of I
      gp120 appearing in serum was less than that expected based on the efflux rate,
      whereas uptake by the cervical nodes was much greater after i. c.v. than after
      i.v. injection of I-gp120. These findings were explained by drainage from the
      brain directly to the cervical lymph nodes through the brain's primitive
      lymphatic system. These lymphatics potentially provide a pathway through which
      CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being
      exposed to circulating antiviral agents.

PMID- 10082881
TI  - Differential effects of mu and kappa opioid antagonists on Fos-like
      immunoreactivity in extended amygdala.
AB  - It was previously reported that systemic administration of the nonselective
      opioid antagonist, naltrexone, induces Fos-like immunoreactivity (FLI) within the
      central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis
      (lateral-dorsal division; BSTLD), nucleus accumbens shell (NACshell) and ventral
      tegmental area (VTA) of free-feeding rats. These findings suggest that cellular
      activity in these brain regions is subject to opioid-mediated inhibitory control
      under basal conditions. Considering the involvement of mesoaccumbens dopamine
      neurons and components of the 'extended amygdala' in motivated behavior and
      reward, it was hypothesized that the induction of c-Fos by naltrexone accounts
      for the motivational-affective consequences of opioid antagonism. In Experiment
      1, naltrexone was administered intracerebroventricularly (i.c.v.; 100 microg) to
      determine whether results obtained in the prior immunohistochemical studies could
      be attributed to blockade of opioid receptors in brain as opposed to peripheral
      tissues that convey visceral sensory inputs to the CeA and BSTLD. Naltrexone
      produced a marked increase in FLI within the CeA and BSTLD, and a moderate
      increase in NACshell. In Experiment 2, the kappa opioid antagonist, nor
      binaltorphimine (Nor-BNI; 20.0 microg, i.c.v.) reproduced the effect of
      naltrexone in BSTLD and CeA, suggesting that the induction of c-Fos in these two
      structures is a consequence of kappa receptor blockade. The selective mu
      antagonist, CTAP (2.0 microg, i.c.v.), reproduced the effect of naltrexone in
      NACshell, suggesting that the induction of c-Fos in this structure is a
      consequence of mu receptor blockade. The functional implications of these results
      are discussed in terms of the known functions of these brain regions and opioid
      receptor types, and the prior observation that chronic food restriction
      eliminates the FLI induced by naltrexone in CeA and BSTLD. It is suggested that
      tonic mu opioid-mediated inhibition in NACshell has a predisposing effect on goal
      approach behavior in general while kappa opioid-mediated inhibition in CeA and
      BSTLD has a predisposing effect on palatability-driven feeding in particular.
      Finally, a possible relationship between food restriction-induced suppression of
      the kappa opioid mechanism in CeA/BSTLD, local CRH function, and sensitization of
      the neural substrate for incentive-motivating effects of abused drugs is
      discussed.

PMID- 10082882
TI  - Sequential changes in anti-GAL-1 staining of the rat organ of Corti following
      amikacin exposure.
AB  - Hair cell loss and a non-functional epithelial reorganization appeared in the
      organ of Corti after acoustic or toxic damage. Moreover, in the drug damaged
      organ of Corti, transient atypical cells were recently described with
      characteristics of both immature hair cells and/or non-sensory epithelial cells.
      The phenotype of these atypical cells has been now investigated by using the
      galectine 1 (GAL-1) antibody. In the normal organ of Corti, this antibody
      recognizes all the epithelial cells except the sensory hair cells and their
      supporting cells. At PD 21, transient atypical cells were not stained by GAL-1
      antibody, suggesting that they were originated from hair cells or their
      supporting cells. Later, the organ of Corti was substituted by an epithelial
      scare, GAL-1 stained. This study also emphasizes the particular resistance of the
      cochlear apex to degeneration after antibiotic intoxication.

PMID- 10082883
TI  - Enhancement of free fatty acid incorporation into phospholipids by choline plus
      cytidine.
AB  - Cytidine and choline, present in cytidine 5'-diphosphate choline (CDP-choline),
      are major precursors of the phosphatidylcholine found in cell membranes and
      important regulatory elements in phosphatide biosynthesis. Administration of CDP
      choline to rats increases blood and brain cytidine and choline levels; this
      enhances the production of endogenous CDP-choline which then combines with fatty
      acids (as diacylglycerol), to yield phosphatidylcholine. We examined the effect
      of providing cytidine and choline on incorporation of free fatty acids into
      phosphatidylcholine and other major phospholipids in PC12 cells. Addition of
      equimolar cytidine and choline (100-500 microM) to [3H]-arachidonic acid (50
      microM, 0.2 microCi, bound to bovine serum albumin) dose-dependently increased
      the accumulations of [3H]-phosphatidylcholine (PtdCho), [3H]-phosphatidylinositol
      (PtdIno) and [3H]-phosphatidylethanolamine (PtdEtn) (by up to 27+/-3%, 16+/-3%
      and 11+/-3%, respectively, means+/-S.E.M.). This effect was seen with 8-18 h of
      incubation. The incorporation of [3H]-oleic acid into [3H]-PtdCho was even more
      enhanced (by up to 42+/-3%) as were the incorporations of [14C]-choline and [3H]
      glycerol. The effects of choline and cytidine were enhanced by 12-O
      tetradecanoylphorbol-13-acetate (TPA, 1 microM), which activates
      CTP:phosphocholine cytidylyltransferase (CT) and facilitates choline uptake.
      Replacing choline by ethanolamine also enhanced the incorporation of [3H]
      arachidonic acid into [3H]-PtdEtn, [3H]-PtdIno and [3H]-PtdCho. Arachidonic acid
      (10-200 microM) alone failed to affect the incorporation of [14C]-choline into
      phosphatidylcholine. We suggest that the increases in phospholipid synthesis
      caused by concurrent cytidine and choline supplementation enhance the
      incorporation of arachidonic acid and certain other fatty acids into the major
      glycerophospholipids. Removing these fatty acids as source of potentially toxic
      oxidation products could contribute to the beneficial effects of CDP-choline in
      treating stroke or other brain damage.

PMID- 10082884
TI  - Sensory gating of the P13 midlatency auditory evoked potential and the startle
      response in the rat.
AB  - The human P1/P50 midlatency auditory evoked potential and the startle response
      (SR) have been used as measures of sensory and sensorimotor gating, respectively.
      In the present study, both prepulse and paired stimulus paradigms were used in
      order to investigate the relationship between sensory gating mechanisms of the
      P13 potential, the putative rodent equivalent of the P1 potential, and those of
      the SR. In addition, these were compared to the properties of the N40 potential,
      another measure of sensory gating. Simultaneous recordings from the vertex (P13
      potential and N40 potential) and neck musculature (SR) showed that (1) in a
      prepulse paradigm, increasing the intensity of the prepulse or decreasing the
      interstimulus interval resulted in increased inhibition of the P13 potential, N40
      potential (to a lesser degree) and the SR (to a greater degree), (2) when using a
      low signal-to-noise ratio between the prepulse intensity and the background
      level, prepulse inhibition of the SR was reduced or absent while that of the P13
      potential was present, (3) the amplitude of the 'prepulse evoked' P13 potential
      was significantly correlated with prepulse inhibition of the P13 potential, the
      N40 potential and the SR, (4) in a paired identical stimulus paradigm, decreasing
      the interstimulus interval resulted in increased habituation of the P13
      potential, N40 potential (to a lesser degree) and the SR, and (5) increasing the
      intensity of the paired stimulation resulted in increased habituation of the P13
      potential and the N40 potential (to a lesser degree), but not of the SR. These
      results demonstrate the presence of prepulse inhibition of the P13 potential, the
      N40 potential and the SR in a parallel manner, but show certain specific
      differences in their responses to parametric changes.

PMID- 10082885
TI  - Modulation of the neuronal nicotinic acetylcholine receptor-channel by the
      nootropic drug nefiracetam.
AB  - The effects of nefiracetam (DM-9384) on the neuronal nicotinic acetylcholine
      (ACh) receptor-channel were studied by the whole-cell patch clamp technique using
      PC12 cells. Nefiracetam had a dual effect on ACh-induced currents: it augmented
      the currents induced by low concentrations (10-30 microM) of ACh and suppressed
      those induced by high concentrations (100-1000 microM) of ACh. These effects were
      reversible after washing with drug-free solution. The stimulating effect of
      nefiracetam was clearly observed at a concentration of 10 microM, and slight
      increases in currents were detected even at 0.1 microM or 1 microM. Nefiracetam
      at 100 microM suppressed the currents induced by a low concentration (10 microM)
      of ACh. The rate of desensitization of ACh-induced current was greatly
      accelerated by nefiracetam, and this effect could not be reversed by washing with
      drug-free solution. When added to the internal pipette solution, the protein
      kinase A inhibitor KT 5720 (0. 6 microM), but not the protein kinase C inhibitor
      calphostin C (0.5 microM), abolished the nefiracetam stimulation of the ACh
      receptor. Pre-incubation of cells with 200 ng/ml pertussis toxin for 24 h also
      abolished the nefiracetam action. Thus, the nefiracetam modulation of the
      neuronal nicotinic ACh receptor-channel is exerted via G proteins and protein
      kinase A. The stimulation of the ACh receptor may be directly related to the
      cognitive enhancing action of nefiracetam.

PMID- 10082886
TI  - Localization of alpha-tocopherol transfer protein in the brains of patients with
      ataxia with vitamin E deficiency and other oxidative stress related
      neurodegenerative disorders.
AB  - Vitamin E (alpha-tocopherol) is an essential nutrient and an important
      antioxidant. Its plasma levels are dependent upon oral intake, absorption and
      transfer of the vitamin to a circulating lipoprotein. The latter step is
      controlled by alpha-tocopherol transfer protein (alpha-TTP), which is a 278 amino
      acid protein encoded on chromosome 8, known to be synthesized in the liver.
      Mutations in alpha-TTP are associated with a neurological syndrome of
      spinocerebellar ataxia, called ataxia with vitamin E deficiency (AVED). Earlier
      studies suggested that alpha-TTP is found only in the liver. In order to
      establish whether alpha-TTP is expressed in the human brain, and what
      relationship this has to AVED, we studied immunohistochemically the presence of
      alpha-TTP in the brains of a patient with AVED, normal subjects, and patients
      with Alzheimer's disease (AD), Down's syndrome (DS), cholestatic liver disease
      (CLD) and abetalipoproteinemia (ABL). The neuropathology of both AD and DS is
      thought to be related in part to oxidative stress. The diseases of AVED, of
      cholestatic liver disease, and of abetalipoproteinemia are thought to be due to
      lack of circulating tocopherol, leading to inadequate protection against
      oxidative damage. We demonstrate the presence of alpha-TTP in cerebellar Purkinje
      cells in patients having vitamin E deficiency states or diseases associated with
      oxidative stress.

PMID- 10082887
TI  - Modulation of striatal neuronal activity by glutamate and GABA: iontophoresis in
      awake, unrestrained rats.
AB  - To examine the effects of glutamate (GLU) and gamma-aminobutyric acid (GABA) and
      their interactions in the striatum under behaviorally relevant conditions, single
      unit recording was combined with microiontophoresis in awake, unrestrained rats.
      Iontophoretically applied GLU (0-40 nA, 20 s) excited all spontaneously active
      neurons in dorsal (caudate-putamen) and ventral (accumbens, core) striatum;
      phasic GLU-induced excitations (mean threshold 19.7 nA) were dose-dependent,
      inversely correlated with rate of basal activity (excitation limit approximately
      65 imp/s), and highly stable during repeated GLU applications. GLU also excited
      silent and sporadically active units, which greatly outnumbered spontaneously
      active cells, and enhanced neuronal excitations associated with movement. Both
      spontaneously active and GLU-stimulated striatal neurons were highly sensitive to
      GABA (0-40 nA, 20 s); most showed short-latency inhibitions during GABA diffusion
      from the pipette (0 nA) and the response quickly progressed to complete silence
      with a small increase in current. The GABA-induced inhibition was current
      dependent, equally strong on spontaneously active and GLU-stimulated units, and
      independent of neuronal discharge rate, but less stable than the GLU-induced
      excitation during repeated drug applications. Prolonged GABA application (0-20
      nA, 2-4 min) reduced basal impulse activity, but was less effective in
      attenuating the neuronal excitations induced by GLU or associated with movement.
      Our data support the role of GLU afferents in the phasic activation of striatal
      neurons and suggest that the effects of GLU strongly depend on the level of
      ongoing neuronal activity. The ability of GABA to modulate both basal and GLU
      evoked activity suggests that GABA, released from efferent collaterals and
      interneurons, plays a critical role in regulating neuronal activity and
      responsiveness to phasic changes in excitatory input.

PMID- 10082888
TI  - The effect of chronic administration of nicotine on antinociception, opioid
      receptor binding and met-enkelphalin levels in rats.
AB  - The effect of chronic nicotine administration on (1) antinociception; (2) opioid
      receptor binding; and (3) met-enkelphalin levels in discrete brain regions in
      rats was investigated. Male and female Sprague-Dawley rats were treated with
      nicotine 0.3 mg/kg, 0.1 mg/kg, or saline three times a day subcutaneously during
      a 14-day protocol. Antinociception was measured by hotplate (HP) test on days 1,
      2, 7, 10 and 14. After completion of the protocol, mu-opioid receptors were
      analyzed by [3H]-DAMGO binding studies and met-enkelphalin levels were determined
      by radioimmunoassay. Results indicated that hot-plate latency increased during
      the first 2 days of nicotine administration for male and female rats who were
      treated with 0.3 mg/kg nicotine. There was an up-regulation of mu-receptors
      (increased Bmax) in the striatum of rats treated with 0.3 mg/kg nicotine,
      compared to 0. 1 mg/kg nicotine and saline groups. An interaction effect of group
      by gender was noted. After 14 days of chronic nicotine administration, met
      enkelphalin levels were significantly lower in striatum and midbrain of animals
      treated with 0.3 mg/kg nicotine, as compared to controls. These results suggest
      that chronic nicotine administration, in doses representative of human smoking,
      produces antinociception initially, and is accompanied by an upregulation of
      micro-opioid receptors in the striatum of rats. In addition, nicotine-induced
      tolerance to antinociception may be associated with a decrease in met-enkelphalin
      level over a period of time.

PMID- 10082889
TI  - Ryanodine receptor modulation of in vitro associative learning in Hermissenda
      crassicornis.
AB  - Classical conditioning of the mollusc, Hermissenda crassicornis, is a model
      system used to study cellular correlates of associative learning. Paired
      presentation of light and turbulence, but not unpaired presentations, causes
      Hermissenda to contract its foot in response to light alone. Intracellular
      recordings from the type B photoreceptors of the Hermissenda eye reveal a
      learning specific increase of input resistance, and a reduction of voltage
      dependent potassium currents, both of which depend on an elevation of
      intracellular calcium. Two previously demonstrated sources of calcium are influx
      through voltage-dependent channels, and release of calcium from intracellular
      stores through the IP3 receptor channel. Both modeling studies and identification
      of memory-related genes using RNA fingerprinting suggest that a third source of
      calcium, release from intracellular stores through the ryanodine receptor, may be
      involved in classical conditioning. We describe here an experiment suggesting
      that this third source of calcium is necessary for the cellular changes
      underlying associative memory storage. Paired presentations of a light stimulus
      with a turbulence stimulus resulted in a significant increase in input
      resistance. Unpaired presentations of light and turbulence did not produce a
      significant increase in input resistance. A third group of nervous systems first
      was incubated in dantrolene to block release of calcium through the ryanodine
      receptor, and then received paired training. There was no change in input
      resistance for this group. The effect of dantrolene on light adaptation of the
      photoreceptor was assessed by measuring the generator potential of a second light
      pulse presented some number of seconds after a first light pulse. The results
      show that at interpulse intervals of 5 s, 10 s and 20 s, the generator potential
      of the dantrolene group is significantly greater than that of the control group.
      These results suggest a role for the ryanodine receptor in both a cellular
      correlate of classical conditioning and light adaptation.

PMID- 10082890
TI  - Prominent binding of the dopamine D3 agonist [3H]PD 128907 in the caudate-putamen
      of the adult rat.
AB  - We have analyzed the binding properties of the selective D3 receptor agonist
      [3H]PD 128907 in 120 days old rats. In tissue sections, we found high numbers of
      binding sites for [3H]PD 128907 both in the islands of Calleja and the caudate
      putamen (Bmax values being 500 and 1000 fmol/mg protein, respectively). The KD
      values were higher in the caudate-putamen than in the islands of Calleja. Similar
      regional differences in Bmax and KD values were observed in membranes from the
      caudate-putamen and the subcortical limbic region. The distribution of [3H]PD
      128907 in adult rats is markedly different from that observed in young rats.
      Taken together, the present results suggest a prominent presence of D3 receptors
      in the caudate-putamen of adult, but not young, rats. Hence, these findings may
      have important physiological, pathophysiological, and clinical implications.

PMID- 10082892
TI  - Real-time monitoring of glutamate transmitter release with anoxic depolarization
      during anoxic insult in rat striatum.
AB  - In vivo continuous real-time measurement of glutamate concentration was performed
      during anoxia using a dialysis electrode. By this method, the temporal resolution
      of the measurement of glutamate concentration was improved due to shortening of
      the time delay compared with the microdialysis method, and changes in the
      glutamate concentration were more clearly represented with greater
      reproducibility. After exposure to anoxia, the glutamate concentration showed
      biphasic changes. A relationship between the DC potential and release of
      glutamate was confirmed by the synchronization of anoxic depolarization (AD) with
      the 1st phase of glutamate release. Since the 1st phase disappeared and AD was
      delayed and suppressed by blocking Ca2+ influx, exocytosis is considered to play
      an important role in the construction of the 1st phase, which had a close
      relation with the occurrence of AD. Moreover, since blocking Ca2+ influx also had
      an effect on the glutamate release from the metabolic pool (2nd phase), reversed
      uptake may be involved with energy failure in the 1st phase, Ca2+ influx into the
      cell and rapid changes of the ionic environment associated with AD.

PMID- 10082891
TI  - Transcranial electrical stimulation (Limoge's currents) potentiates the
      inhibition of righting reflex induced by droperidol in rats.
AB  - The effects of transcranial electrical stimulation (TCES) on droperidol-treated
      rats were evaluated using the righting reflex latency (RRL) test. TCES (high
      frequency (HF)-166 kHz, intermittent-100 Hz current) delivered through three
      electrodes (a negative electrode placed between the eyebrows and positive
      electrodes located in the retro-mastoid region) was shown to potentiate the
      inhibition of righting reflex induced by droperidol. This potentiation was found
      to depend on the dose of the drug, the characteristics of the current delivered
      and the duration of stimulation. We also observed that TCES-induced potentiation
      of inhibition of righting reflex produced by droperidol injection was not
      reversed: (i) after naltrexone administration, (ii) when measures were performed
      on p-chlorophenylalanine (pCPA)-treated animals. These results suggest that,
      under the experimental conditions: (i) TCES does not interact with opioid
      endogenous to potentiate droperidol effects, (ii) the effect of TCES on
      dopaminergic system prevails against TCES action on serotonergic system. Though
      these findings enlarge the comprehension of TCES effects on the central nervous
      system, further investigations are necessary to elucidate TCES mechanisms.

PMID- 10082893
TI  - Cellular dynamics of corneal wound re-epithelialization in the rat. I. Fate of
      ocular surface epithelial cells synthesizing DNA prior to wounding.
AB  - The fate of ocular surface epithelial cells in response to injury of the cornea
      was examined. Corneal epithelial cells were labeled during DNA synthesis with
      [3H]thymidine 1 h prior to wounding. A 3-mm diameter epithelial defect was made
      in the center of the rat cornea, with the basement membrane remaining intact.
      Within 12 h of abrasion, labeled cells were detected in the regenerating surface.
      At 18 h, there was a 2.7- and 17-fold increase of labeled basal and suprabasal
      cells, respectively, in the epithelium adjacent to the wound, and at 24 and 30 h
      there was an excessive number of cell layers (up to 7) at the margin of the
      abrasion. Re-epithelialization progressed as a gradient of cell layers that
      became diminished towards the center of the wound. Completion of layers 1, 2, 3,
      and 4 were recorded at 24, 30, 36, and 72 h, respectively. No changes in the
      labeling index of the limbus or conjunctiva were noted. These results suggest
      that processes of centripetal and vertical migration, as well as events related
      to cell division, in the uninjured corneal surface are not impeded by wounding of
      the corneal epithelium. However, wound healing appears to require cells with a
      basal phenotype, presumably because of this cell type's migratory capability.

PMID- 10082894
TI  - Sensitization of amphetamine-induced stereotyped behaviors during the acute
      response: role of D1 and D2 dopamine receptors.
AB  - During the response to an injection of amphetamine, rapid changes occur in the
      ability of the drug to induce stereotyped behaviors. This enhanced responsivity
      does not involve changes in the caudate-putamen or nucleus accumbens
      extracellular dopamine response, but appears to require activation of dopamine
      receptors. In the present studies we examined the role that D1 and D2 dopamine
      receptors might play in the development and expression of the enhanced stereotypy
      response. In one series of experiments we used the dopamine agonists, SKF 82958
      and quinpirole as relatively selective probes at D1 and D2 dopamine receptors,
      respectively, to test for changes in dopamine receptor sensitivity following a
      pretreatment ('priming') with 4.0 mg/kg amphetamine. Doses of both SKF 82958 and
      quinpirole which were sub-threshold to induce perseverative behaviors in control
      animals, promoted stereotyped behaviors in amphetamine-primed animals, suggesting
      an enhanced sensitivity of both D1 and D2 receptors. In a second series of
      experiments, we sought to determine whether priming with these relatively
      selective dopamine receptor agonists, as well as the mixed D1/D2 agonist,
      apomorphine, would result in an enhanced stereotypy response to the subsequent
      administration of non-stereotypy producing doses of amphetamine (0.5-1.5 mg/kg).
      Priming with the dopamine receptor agonists each resulted in an enhanced
      amphetamine-induced stereotypy response. These results indicate that both D1 and
      D2 dopamine receptors contribute to both the development and the expression of
      the altered stereotypy responsivity, though several dose- and time-related
      observations suggest that other mechanisms likely contribute as well. Because
      these changes are apparent during the amphetamine response, they may have
      important implications for the evolving behavioral alterations which result when
      stimulants are administered in a binge pattern of drug abuse.

PMID- 10082895
TI  - Expression and localisation of CYP2D enzymes in rat basal ganglia.
AB  - P450 enzymes in the CYP2D subfamily have been suggested to contribute to the
      susceptibility of individuals in developing Parkinson's disease. We have used
      specific anti-peptide antisera and peroxidase immunohistochemistry to investigate
      the expression of CYP2D enzymes in the rat brain and some possible factors that
      may affect their regulation. In male Wistar rats, CYP2D1 was not detected in the
      basal ganglia or in any other brain region. CYP2D2 was weakly expressed within
      neurones of the subthalamic nucleus, substantia nigra and interpeduncular nucleus
      as well as in the hippocampus, dentate gyrus, red nucleus and pontine nucleus.
      CYP2D3 and CYP2D4 were absent from the basal ganglia, although moderate amounts
      of CYP2D3 were detected within fibres of the oculomotor root, and very low levels
      of CYP2D4 were present in white matter tracts. In contrast, CYP2D5 was
      extensively expressed in the basal ganglia, including neurones in the subthalamic
      nucleus, substantia nigra and interpeduncular nucleus, as well as other areas of
      the brain, including the ventral tegmental area, piriform cortex, hippocampus,
      dentate gyrus, medial habenular nucleus, thalamic nucleus and pontine nucleus.
      Lesioning of the nigro-striatal tract to cause almost a complete loss of tyrosine
      hydroxylase containing neurones in the substantia nigra, also reduced the number
      of neurones expressing CYP2D5 by 50%, indicating that CYP2D5 is expressed in
      dopaminergic neurones. Castration of pre-pubertal or adult Wistar rats had no
      effect on the number of CYP2D5-positive neurones in the substantia nigra.
      Although Dark Agouti rats lack hepatic CYP2D2, expression in the midbrain was
      similar to that of Wistar rats; furthermore, there was no difference in
      expression or distribution between male and female rats. In contrast to naive
      rats, extensive expression of CYP2D4 was found throughout the basal ganglia and
      in other brain nuclei in Wistar rats treated with not only clozapine, but also
      saline, suggesting that CYP2D4 may be induced as a result of mild stress. The
      function of CYP2D enzymes in the brain remains unknown, but their selective
      localisation suggests a physiological role in neuronal activity and in adaptation
      to abnormal situations.

PMID- 10082896
TI  - Cardiovascular responses to microinjections of excitatory amino acids into the
      area postrema of the rat.
AB  - Although, area postrema (AP) as been implicated in the regulation of
      cardiovascular function, there is no consensus regarding the type of responses
      elicited by stimulation of this brain structure. Microinjections (50 nl) of
      smaller concentrations of excitatory amino acid receptor agonists (e.g., NMDA, KA
      and trans-ACPD, 10 microM each) into the AP elicited pressor and tachycardic
      responses in unanesthetized decerebrate as well as urethane-anesthetized rats.
      Microinjections of higher concentrations (e.g., 50 microM NMDA) of excitatory
      amino acids (EAAs) into the AP elicited an initial pressor and tachycardic
      response which was followed by a depressor and bradycardic response; when high
      concentrations of NMDA were microinjected into the AP, enough concentration may
      have reached the nucleus tractus solitarius (nTS) to elicit depressor and
      bradycardic responses. Alternatively, high concentrations of NMDA may excite
      known projections from AP to the nTS.

PMID- 10082897
TI  - Suggestive evidence for inhibitory effects of galanin on mesolimbic dopaminergic
      neurotransmission.
AB  - The objective was to examine effects of galaninrat on forebrain monoamine
      synthesis and on spontaneous locomotor activity in the rat. The rate of monoamine
      synthesis was estimated by measuring the accumulation of l-DOPA and 5-HTP,
      following inhibition of cerebral aromatic l-amino acid decarboxylase by means of
      NSD-1015 (100 mg kg-1 i.p.), after i.c.v. or intracerebral administration of
      galanin in adult male Wistar rats. Spontaneous locomotor activity was observed in
      an automated open-field arena ( approximately 0.5 m2). The i.c.v. administration
      of galanin (0.5-5.0 nmol bilaterally) produced a dose-dependent, statistically
      significant, increase in DOPA accumulation throughout the neostriatum, and in the
      olfactory bulb, indicating an increase in the rate of DA synthesis. No increase
      was observed in brain areas where noradrenaline is the predominant catecholamine,
      such as the neocortex or the ventral hippocampus. In addition, there was a
      tendency for an increase in 5-HTP accumulation in the dorso-lateral neostriatum
      and in the accumbens. The same i.c.v. administration of galanin produced a dose
      dependent, and statistically significant, decrease in spontaneous locomotor
      activity. The effect on forebrain DA synthesis could also be produced by local
      bilateral application of galanin (2x1 nmol) into the ventral tegmental area, but
      not the nucleus accumbens (2x2 nmol). There were no effects on forebrain DOPA or
      5-HTP accumulation by the local application of galanin into the locus coeruleus,
      or into the dorsal raphe nucleus. It is concluded that the neuropeptide galanin
      modulates forebrain dopaminergic neurotransmission. The effect appears to be
      mediated at the somato-dendritic level of the meso-neostriatal pathway, and could
      perhaps be utilized to normalize perturbations ascribed to dysfunction in this
      neuronal pathway, such as schizophrenia.

PMID- 10082898
TI  - Effect of pre-emptive NMDA antagonist treatment on long-term Fos expression and
      hyperalgesia in a model of chronic neuropathic pain.
AB  - The unilateral sciatic nerve chronic constriction injury (CCI) model of Bennett
      and Xie [G.J. Bennett, Y.-K. Xie, A peripheral neuropathy in rat that produces
      disorders of pain sensation like those seen in man, Pain, 33 (1988) 87-108] shows
      features of a neuropathic pain state. We examined mechanical hyperalgesia and Fos
      protein staining in the lumbar spinal cord 1, 7, 14 and 28 days after unilateral
      CCI to the sciatic nerve or sham operation. In addition, we examined the effect
      of the NMDA antagonist MK-801 (0.3 mg/kg s.c. administered 30 min prior to and 6
      h following operation) on Fos expression and hyperalgesia at 28 days. CCI animals
      were hyperalgesic compared to the sham operated animals at 14 and 28 days post
      injury. MK-801 reduced hyperalgesia by 68% in CCI animals on day 28 (p=0.0001).
      In the spinal cord, Fos positive cells were present bilaterally in deeper laminae
      in both sham and CCI animals at all time points examined. Relatively few Fos
      positive cells were present in laminae 1-2 at any time point examined. At days 1
      and 7, there were increased numbers of Fos positive cells ipsilaterally in the
      deeper laminae of the spinal cord in CCI animals compared to sham animals, but by
      14 and 28 days Fos counts were similar in sham and CCI despite the obvious
      behavioural differences between the two groups. Fos counts ipsilateral to the
      injury in laminae 3-10 correlated with hyperalgesia scores in the CCI but not
      sham animals. Analysis at the 28-day time point showed that MK-801 differentially
      affected Fos expression: MK-801 significantly reduced the Fos count bilaterally
      in laminae 3-10 in the CCI but not in the sham group animals. These results
      indicate that Fos expression is initiated by different peripheral and central
      mechanisms following nerve injury or sham operation.

PMID- 10082899
TI  - Effect of post-injury NMDA antagonist treatment on long-term Fos expression and
      hyperalgesia in a model of chronic neuropathic pain.
AB  - Chronic constriction injury (CCI) of the sciatic nerve results in persistent
      mechanical hyperalgesia together with Fos protein expression in the lumbar spinal
      cord. We have examined the relationship between mechanical hyperalgesia and Fos
      expression within the lumbar spinal cord on days 14, 35 and 55 after either CCI
      or sham operation. To determine the role of NMDA receptor mechanisms in the
      maintenance of hyperalgesia and Fos expression, the NMDA antagonist MK-801 (0.3
      mg kg-1 s.c.) was administered daily on days 28 to 34 after operation. CCI
      animals developed unilateral hind limb hyperalgesia that persisted unchanged from
      days 14 to 55 of the study. MK-801 treatment reduced hyperalgesia by 57% (p=0.02)
      on day 35 in CCI animals but did influence hyperalgesia at day 55. In the spinal
      cord, Fos positive cells were present bilaterally throughout laminae 3-10 at all
      time points examined in both CCI and sham group animals. Fos counts ipsilateral
      to the side of injury in laminae 3-10 correlated significantly with hyperalgesia
      scores in the CCI but not sham animals. MK-801 treatment resulted in a
      suppression of Fos expression in ipsilateral laminae 3-4 (p=0.0017) and laminae 5
      10 (p=0.0026) of CCI animals on day 35. Fos expression in sham group animals was
      not inhibited by MK-801 treatment at day 35. These results indicate that Fos
      expression is maintained by differing mechanisms following nerve injury or sham
      operation. The functional consequences of Fos expression following nerve injury
      and sham operation are discussed.

PMID- 10082900
TI  - Changes in brain corticotropin-releasing factor messenger RNA expression in aged
      Fischer 344 rats.
AB  - Adaptation in aging may become impaired from abnormal expression of corticotropin
      releasing factor (CRF) and altered CRF receptor function. In this study, we
      measured CRF mRNA levels in Fischer 344 rats at various ages. The brains of these
      rats were processed for in situ hybridization. Relative to 3-month-old rats,
      levels of CRF mRNA were significantly decreased in the following brain areas at
      the following ages: at 24 months in the paraventricular hypothalamus, at 11, 17,
      and 24 months in the amygdala and at 17 and 24 months in the bed nucleus of the
      stria terminalis. These changes may contribute to impaired adaptations to stress,
      cognitive decline and other pathophysiological processes during aging.

PMID- 10082901
TI  - Tonic firing of rat nucleus accumbens neurons: changes during the first 2 weeks
      of daily cocaine self-administration sessions.
AB  - Activity of single neurons in the nucleus accumbens (NAcc) of rats was recorded
      extracellularly on the 2nd and 15th days of intravenous cocaine self
      administration. Each of the two electrophysiological recording sessions consisted
      of three successive phases: a pre-drug baseline recording period, a cocaine self
      administration session, and a post-drug recording period. Firing of individual
      neurons was typically inhibited during the self-administration session, relative
      to the pre-drug period. The inhibition was greater on the 15th day relative to
      the 2nd day. Additionally, firing rates during the pre-drug period and the self
      administration session were typically lower on the 15th day as compared to the
      2nd day. The present data are consistent with previous acute electrophysiological
      findings and are in line with the hypothesis that repeated drug self
      administration engenders changes in the mesoaccumbens pathway that contribute to
      drug addiction.

PMID- 10082902
TI  - Anatomical basis for cannabinoid-induced antinociception as revealed by
      intracerebral microinjections.
AB  - Cannabinoids suppress behavioral and neurophysiological responses to noxious
      stimuli in rodents when administered systemically. The purpose of this study was
      to extend previous studies of the site of cannabinoid analgesia. Rats were tested
      in the tail flick test before and after microinjections of the cannabinoid
      agonist WIN55, 212-2 (5 microg) into one of 17 different brain regions. WIN55,212
      2 significantly elevated tail-flick latencies when injected into the amygdala,
      the lateral posterior and submedius regions of the thalamus, the superior
      colliculus and the noradrenergic A5 region. By contrast, pain behavior was
      unaffected by microinjections of the cannabinoid into the other 11 areas examined
      (prefrontal cortex, nucleus accumbens, lateral hypothalamus, substantia nigra,
      cuneiform nucleus, anterior pretectal, intralaminar, parafasicular, posterior,
      thalamic nuclei, as well as the ventral medial, ventral lateral nuclei in the
      posterior thalamus).

PMID- 10082903
TI  - Steroidal regulation of portal arginine-vasopressin levels in aged Fischer 344
      rats.
AB  - Levels of hypophysial portal arginine-vasopressin (AVP), plasma ACTH and plasma
      corticosterone (B) were measured in four and 24 month old Fischer 344 rats.
      Portal levels of AVP were lower in older rats whereas plasma ACTH levels were
      elevated. Older rats given adrenalectomies with physiologic replacement doses of
      B exhibited levels of AVP, but not ACTH, which were comparable to that observable
      in younger rats. The findings suggest that altered AVP, but not ACTH, can be
      accounted for by higher B levels which are commonly demonstrable in aging rats.

PMID- 10082904
TI  - Sertoli cells enhance the survival of co-transplanted dopamine neurons.
AB  - One of the major issues in neural transplantation is the low survival rate (<5%)
      of transplanted dopamine (DA) neurons [3]. Recently it has been shown that it is
      possible to enhance the survival of these neurons, which in turn may decrease the
      amount of tissue that is required for each transplantation patient. The present
      paper demonstrates a novel approach for enhancing neuronal survival by co
      transplantation of neuronal tissue with Testis-derived Sertoli cells (SC). This
      strategy could improve neuronal survival through the provision of trophic
      support.

PMID- 10082905
TI  - Dehydration modifies somal CRH immunoreactivity in the rat hypothalamus: an
      immunocytochemical study in the absence of colchicine.
AB  - Corticotropin-releasing hormone immunoreactive (CRH-ir) neurons were examined in
      the hypothalamus of euhydrated and dehydrated rats without using colchicine. CRH
      ir cells were observed in the lateral hypothalamus, retrochiasmatic, and in
      magnocellular parts of the supraoptic and paraventricular hypothalamic nucleus
      (PVH) in dehydrated but not euhydrated animals. However, CRH-ir neurons were
      decreased in the medial parvicellular part of the PVH. These results indicate
      that altered CRH mRNA levels previously reported in dehydrated animals translate
      into changes in peptide immunoreactivity.

PMID- 10082906
TI  - Decrease in stress-induced c-Fos-like immunoreactivity in the lateral septal
      nucleus of learned helpless rats.
AB  - Inescapable stress can induce learned helplessness in many species of animals.
      Learned helplessness is a phenomenon which has some behavioral and
      neurotransmitter analogies with human clinical depression. Stress can also induce
      the expression of immediate early genes, including c-fos in many areas of the
      central nervous system. We examined stress-induced c-Fos-like immunoreactivity
      (FLI) using the learned helplessness paradigm. Naive rats showed significantly
      higher FLI than the tested groups in all the amygdaloid regions and in the
      hypothalamic paraventricular nucleus. However, in the lateral septal nucleus,
      helpless animals showed significantly reduced FLI in response to stress, compared
      to the other groups. These, and other previous data, highlight the importance of
      the septal area in mediating behavioral responses to inescapable stress.

PMID- 10082907
TI  - Occlusion of the MCA by an intraluminal filament may cause disturbances in the
      hippocampal blood flow due to anomalies of circle of Willis and filament
      thickness.
AB  - We examined blood flow changes and histology in the hippocampus induced by
      occlusion of the middle cerebral artery (MCA) by a filament in Swiss albino and
      SV-129 mice (n=67) and in Wistar rats (n=64). Filling cerebral arteries with
      carbon black revealed that one or both posterior communicating arteries were
      hypoplastic in 50% of Swiss mice. Ischemic changes were detected in the
      ipsilateral hippocampus with 2,3,5-triphenyl tetrazolium chloride or hematoxylin
      and eosin staining when these mice were subjected to 2-h MCA occlusion and 22-h
      reperfusion. No such abnormalities were found in SV-129 mice and Wistar rats
      (except one). The hippocampal blood flow dropped to 60+/-2.3% of the baseline in
      mice with a normal circle of Willis but to 37+/-4.2% in those with an incomplete
      circle when the MCA was occluded with a 6/0 nylon filament. When an 8/0 filament
      was used, no flow change in mice with a normal circle but a decrease to 60+/-2%
      in those with an incomplete circle was observed. A flow drop to 63+/-4% was also
      seen in Wistar rats when a 3/0 filament used. These data demonstrate that
      occlusion of the MCA by a thick filament may cause flow reduction in the
      hippocampus, which may be severe enough to lead to infarction if the circle of
      Willis is anomalous.

PMID- 10082908
TI  - Autoradiographic localization of alpha5 subunit-containing GABAA receptors in rat
      brain.
AB  - Multiple subtypes of GABAA receptors are expressed in the rat central nervous
      system (CNS). To determine the distribution and proportion of alpha5 subunit
      containing receptors, quantitative autoradiographic analyses were performed with
      both [3H]L-655,708 and [3H]Ro15-1788, an alpha5 selective and a non selective
      benzodiazepine binding site ligand, respectively. High densities of [3H]L-655,708
      binding sites were observed in hippocampus and olfactory bulb, where alpha5
      receptors accounted for 20-35% of total [3H]Ro15-1788 binding sites. Low levels
      of [3H]L-655,708 sites were associated with the cortex as well as amygdala,
      thalamic, hypothalamic and midbrain nuclei. These observations indicate that
      although [3H]L-655,708 binding sites have an overall low expression in rat CNS,
      they may contribute significantly to GABAergic inhibition in specific brain
      regions.

PMID- 10082909
TI  - Load signalling by cockroach trochanteral campaniform sensilla.
AB  - A major problem in sensory motor integration is to delineate how forces acting
      upon a leg are encoded and regulated in the control of posture and locomotion. We
      have studied responses of the trochanteral campaniform sensilla, the largest
      array of force detecting mechanoreceptors in the cockroach leg. Afferents from
      two groups of sensilla (Groups 3 and 4) encode forces applied to the leg in the
      plane of joint movement of the coxo-trochanteral joint. The receptors within
      Group 3 exhibit fixed patterns of recruitment that could differentially indicate
      when force levels are adequate to provide support and propulsion during walking.

PMID- 10082910
TI  - Prolactin-releasing peptide-immunoreactivity in A1 and A2 noradrenergic neurons
      of the rat medulla.
AB  - Distribution of prolactin-releasing peptide-like immunoreactivity (PrRP-LI) was
      investigated in the rat medulla with the use of a rabbit polyclonal antiserum
      against the human PrRP-31 peptide. PrRP-positive neurons were noted mainly in two
      areas of the caudal medulla: ventrolateral reticular formation and commissural
      nucleus of the nucleus of the solitary tract (NTS), corresponding to the A1 and
      A2 areas. PrRP-LI neurons were absent in the medulla rostral to the area
      postrema. Double-labeling the sections with PrRP antisera and tyrosine
      hydroxylase (TH) monoclonal antibodies revealed extensive colocalization of PrRP-
      and TH-like immunoreactivity (TH-LI) in neurons of the A1 and A2 areas. Our
      results show that PrRP-LI is expressed in a population of A1 and A2 noradrenergic
      neurons of the rat caudal medulla.

PMID- 10082911
TI  - Higher frequency of dicentrics and micronuclei in peripheral blood lymphocytes of
      cancer patients.
AB  - The presence of dicentric chromosome (DC) and micronuclei (MN) frequency in the
      peripheral blood lymphocytes of 25 cancer patients prior to chemo and
      radiotherapy and 21 healthy volunteers were studied. The overall DC and MN showed
      significantly higher frequency compared to those obtained in normal healthy
      volunteers (p<0.0001). However, among 25 patients only 15 showed a higher
      frequency of DC aberration, nine patients showed the presence of minutes (M) and
      seven patients showed chromatid breaks (ChB). The reasons for the higher
      frequency of aberration observed in these cancer patients are discussed in this
      paper.

PMID- 10082912
TI  - Chromosomal sensitivity to X-ray irradiation during the G2 phase in lymphocytes
      of patients with hereditary cutaneous malignant melanoma as compared to healthy
      controls.
AB  - Recent reports have suggested that elevated chromosomal aberration yields
      following X-ray irradiation of skin fibroblasts and peripheral lymphocytes in the
      G2 phase of the cell cycle are characteristic of affected members of cancer-prone
      families. These studies propose that the phenomenon is a consequence of impaired
      caffeine- and arabinofuranosylcytosine (ara-C)-sensitive DNA repair and might be
      a useful indicator of genetic susceptibility to cancer. We have tested G2
      chromosomal X-ray sensitivity in peripheral blood lymphocytes from members of
      kindreds with hereditary cutaneous malignant melanoma (HCMM) combined with the
      dysplastic nevus syndrome (DNS), disorders in which susceptibility to skin cancer
      is inherited in an autosomal dominant pattern. In the assay lymphocytes from
      patients with HCMM/DNS exhibited responses indistinguishable from normal healthy
      controls. Furthermore, the radiation-induced aberration yields were potentiated
      to the same strong extent by post-treatments with caffeine, or a combination of
      ara-C and hydroxyurea, both in lymphocytes from individuals with HCMM/DNS and
      lymphocytes from healthy controls. Thus, lymphocytes of affected patients with
      HCMM/DNS do not have an increased sensitivity to X-ray irradiation in the G2
      phase of the cell cycle.

PMID- 10082913
TI  - Melatonin and protection from whole-body irradiation: survival studies in mice.
AB  - The radioprotective ability of melatonin was investigated in mice exposed to an
      acute whole-body gamma radiation dose of 815 cGy (estimated LD50/30 dose). The
      animals were observed for mortality over a period of 30 days following
      irradiation. The results indicated 100% survival for unirradiated and untreated
      control mice, and for mice treated with melatonin or solvent alone. Forty-five
      percent of mice exposed to 815 cGy radiation alone, and 50% of mice pretreated
      with solvent and irradiated with 815 cGy were alive at the end of 30 days.
      Irradiated mice which were pretreated with 125 mg/kg melatonin exhibited a slight
      increase in their survival (60%) (p=0.3421). In contrast, 85% of irradiated mice
      which were pretreated with 250 mg/kg melatonin were alive at the end of 30 days
      (p=0.0080). These results indicate that melatonin (at a dose as high as 250
      mg/kg) is non-toxic, and that high doses of melatonin are effective in protecting
      mice from lethal effects of acute whole-body irradiation.

PMID- 10082914
TI  - Mutant yields and mutational spectra of the heterocyclic amines MeIQ and PhIP at
      the S1 locus of human-hamster AL cells with activation by chick embryo liver
      (CELC) co-cultures.
AB  - Cooking meat and fish at high temperature creates heterocyclic amines (HA)
      including 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine (PhIP). Several HA are mutagens in the Ames'
      S9/Salmonella assay. While PhIP is a substantial Ames' test mutagen, it is 1000
      fold less active than the extraordinarily potent MeIQ. In contrast, MeIQ is
      significantly less mutagenic than PhIP in several mammalian cell assays,
      especially in repair-deficient Chinese hamster ovary (CHO) cells. HA are suspect
      human carcinogens on the basis of (i) epidemiological evidence, (ii) induction of
      tumors in rodents and monkeys, (iii) DNA adduct formation and (iv) mutagenic
      capacity. In this study, MeIQ and PhIP were significant mutagens at the S1 locus
      of co-cultivated human/hamster hybrid AL cells following metabolic activation by
      beta-napthoflavone (betaNF)-induced chick embryonic liver cultures (CELC). MeIQ
      was more mutagenic than PhIP in the CELC+AL cell assay. The mutant response
      curves increase with dose and then plateau (PhIP), or decrease (MeIQ). The
      inflections in these response curves coincide with dose-dependent decreases in
      cytochrome CYP1A1 activity. Molecular analysis of S1- mutants indicates that a
      substantial fraction, >65%, of the mutations induced by PhIP are deletions of 4.2
      to 133 (Mbp); half are larger than 21 Mbp. Mutations induced by MeIQ were
      smaller, most (56%) being less than 5.7 Mbp. When appropriate metabolic
      activation is combined with a target locus, which can detect both small and large
      chromosomal mutations, both MeIQ and PhIP are significant mutagens and clastogens
      in repair proficient mammalian cells.

PMID- 10082915
TI  - The Big Blue(R) transgenic mouse mutation detection assay: the mutation pattern
      of sectored mutant plaques.
AB  - There are mutational artifacts in the Big Blue(R) assay and it is important to
      characterize the source and nature of these mutations. Differences were reported
      in the mutation patterns of a small sample of 23 sectored and 91 circular mutant
      plaques derived from skin using the Big Blue(R) transgenic mouse mutation
      detection system [G. R. Stuart, N.J. Gorelick, J.L. Andrews, J.G. de Boer, B.W.
      Glickman, The genetic analysis of lacI mutations in sectored plaques from Big
      Blue transgenic mice, Environ. Mol. Mutagen 28 (1996) 385-392.]. We have extended
      these observations by analyzing 46 sectored and 224 circular mutant plaques
      derived from seven tissues. The frequency of sectored mutant plaques is estimated
      to be 16% with no significant variation with tissue type. However, the patterns
      of mutation for sectored mutants and mouse-derived mutations differed
      significantly (p=0.04). Base substitutions in sectored mutant plaques do not show
      the asymmetries found in circular mutants consistent with integration of a GC
      rich transgene into the AT rich mammalian genome. Sectored mutants have mutation
      patterns consistent with a mixture of mouse, in vitro and Escherichia coli
      derived mutations. Data on the relative frequencies of different mutant plaque
      morphologies suggests that overlapped plaques are substantially contaminated by
      sectored plaques at recommended plating densities.

PMID- 10082916
TI  - Use of log-linear analysis to construct explanatory models for TDBP- and AFB1
      induced mutation spectra in lacI transgenic animals.
AB  - Mutation spectra recovered from lacI transgenic animals exposed in separate
      experiments to tris-(2,3-dibromopropyl)phosphate (TDBP) or aflatoxin B1 (AFB1)
      were examined using log-linear analysis. Log-linear analysis is a categorical
      procedure that analyses contingency table data. Expected contingency table cell
      counts are estimated by maximum likelihood as effects of main variables and
      variable interactions. Evaluation of hierarchical models of decreasing complexity
      indicates when significant explanatory power is lost by the sequential omission
      of interactions between variables. Use of this technique allows construction of
      the most parsimonious models to account for mutation spectra obtained in the two
      experiments. The resulting statistical models are consistent with previous
      analyses of these data and with biological explanations for causes of the
      observed spectra.

PMID- 10082917
TI  - Inhibition of radiation-induced DNA damage in plasmid pBR322 by chlorophyllin and
      possible mechanism(s) of action.
AB  - Naturally occurring compounds capable of protecting DNA against ionizing
      radiation and chemical mutagens have considerable potential for prevention of
      mutation-based health impairment including cancer and other degenerative
      diseases. Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, has
      been examined for its ability to protect DNA against radiation induced strand
      breaks using an in vitro plasmid DNA system. Gamma-radiation, up to a dose of 6
      Gy (dose rate 1.25 Gy/min), induced a dose-dependent increase in single-strand
      breaks (ssbs) in plasmid pBR322 DNA. CHL per se did not induce, but inhibited
      radiation-induced ssbs in a concentration-dependent manner; 500 microM giving
      about 90% protection. The protection afforded by CHL was comparatively less than
      that of trolox, a water-soluble analogue of alpha-tocopherol. To elucidate the
      underlying mechanism(s), reaction of CHL with the radiation-derived hydroxyl
      radical (.OH) and deoxyribose peroxyl radical (ROO.) was studied by pulse
      radiolysis. CHL exhibited a rate constant of 6.1+/-0.4x109 M-1 s-1 with.OH and
      5.0+/-1.3x107 M-1 s-1 with ROO. To our knowledge, this is the first report
      providing direct evidence of free radical-scavenging properties of CHL. The
      results showed that CHL, effectively protects plasmid DNA against ionizing
      radiation, in an in vitro system independent of DNA repair or other cellular
      defense mechanisms. The ability of CHL to scavenge. OH and ROO., may contribute
      to its protective effects against radiation induced DNA damage in the pBR322
      system.

PMID- 10082918
TI  - Polymerase chain reaction-based deletion screening of bisulfite (sulfur dioxide)
      enhanced gpt-mutants in CHO-AS52 cells.
AB  - In this study, we have examined the mutagenicity of bisulfite (sulfur dioxide) at
      the xathine-guanine phosphoribosyl transferase locus (gpt) in the pSV2 gpt
      transformed CHO cell line, AS52. Our results provide evidence for bisulfite as a
      weak gene mutagen because the chemical at high doses and at high cytotoxicity
      causes a 4-fold increase in mutant frequency (MF) and less than a doubling of the
      gpt gene deletion frequency compared to control. We suggest that the increase of
      MF in bisulfite-treated cells results from bisulfite activity,as a comutagen,
      enhancing the induction effect of unknown endogenous or exogenous factors on
      spontaneous mutagenesis of AS52 cells. For the spontaneous, 5 mM bisulfite- and
      10 mM bisulfite-enhanced spontaneous mutants in AS52 cells, the percentage of
      total deletion mutations of the gpt gene is 36%, 44% and 65%, respectively

PMID- 10082919
TI  - Teniposide (VM-26) treatment enhances the radiation-induced micronuclei in the
      bone marrow of mouse.
AB  - The effect of Teniposide (VM-26) pretreatment was studied on the micronuclei
      induction in the bone marrow of mice exposed to 0, 0.5, 1, 2 and 3 Gy of gamma
      radiation at 12, 24 and 36 h post-irradiation. Administration of 0.05 mg/kg body
      weight of VM-26 to mice before irradiation resulted in the significant
      enhancement of micronucleated polychromatic erythrocytes (MPCE) at 12, 24 and 36
      h post-irradiation. Highest elevation in the frequency of MPCE was observed in VM
      26+irradiation group after exposure to 0.5 Gy when compared to concurrent
      DDW+irradiation group. This increase was two fold higher in VM-26+irradiation
      group at 12 and 24 h, while it was 3 fold higher at 36 h post-irradiation
      compared to DDW+irradiation group. The peak frequency of MPCE was observed at 24
      h post-irradiation in both groups, which declined thereafter. The frequency of
      micronucleated normochromatic erythrocytes (MNCE) increased in a dose dependent
      manner in both DDW+irradiation and VM-26+irradiation groups. However, the
      frequency of MNCE was significantly higher in the latter when compared to the
      former group. The frequency of MNCE exhibited a continuous elevation up to 36 h
      post-irradiation in both DDW+irradiation and VM-26+irradiation groups. Treatment
      of mice with teniposide before irradiation resulted in a significant decline in
      the PCE/NCE ratio compared to DDW+irradiation group. The PCE/NCE ratio continued
      to decline up to 36 h post-irradiation in both the groups. The dose response for
      MPCE and PCE/NCE ratio was linear quadratic, while it was linear for MNCE.

PMID- 10082920
TI  - Radiation-induced malformations after exposure of murine germ cells in various
      stages of spermatogenesis.
AB  - We studied radiation effects in day 19 fetuses of the mouse strain
      'Heiligenberger' after exposure (2.8 Gy, 137 Cs gamma rays, dose rate 0.28 Gy/h)
      of their fathers. We observed an increased lethality (exclusively due to
      preimplantation death and early resorptions) after exposure of all stages of
      spermatogenesis with the exception of early spermatogonia. In addition, there was
      a significant increase in the frequency of malformed fetuses (gastroschises
      only); this increase was observed primarily after exposure of the meiotic stages.

PMID- 10082921
TI  - Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu(II).
AB  - Quercetin, one of flavonoids, has been reported to be carcinogenic. There have
      been no report concerning carcinogenicity of kaempferol and luteolin which have
      structure similar to quercetin. DNA damage was examined by using DNA fragments
      obtained from the human p53 tumor suppressor gene. Quercetin induced extensive
      DNA damage via reacting with Cu(II), but kaempferol and luteolin induced little
      DNA damage even in the presence of Cu(II). Excessive quercetin inhibited copper
      dependent DNA damage induced by quercetin. Bathocuproine, a Cu(I)-specific
      chelator, catalase and methional inhibited the DNA damage by quercetin, whereas
      free hydroxyl radical scavengers did not. Site specificity of the DNA damage was
      thymine and cytosine residues. The site specificity and the inhibitory effects
      suggested that DNA-copper-oxygen complex rather than free hydroxyl radical
      induced the DNA damage. Formation of 8-oxodG by quercetin increased extensively
      in the presence of Cu(II), whereas 8-oxodG formation by kaempferol or luteolin
      increased only slightly. This study suggests a good relationship between
      carcinogenicity and oxidative DNA damage of three flavonoids. The mechanism of
      DNA damage by quercetin was discussed in relation to the safety in cancer
      chemoprevention by flavonoids.

PMID- 10082922
TI  - Genomic instability in silica- and cadmium chloride-transformed BALB/c-3T3 and
      tumor cell lines by random amplified polymorphic DNA analysis.
AB  - Our earlier studies using random amplified polymorphic DNA (RAPD) analysis have
      shown genetic instability in human lung cancer tissues. Here we have investigated
      the potential for genetic instability in silica- and cadmium chloride (CdCl2)
      transformed BALB/c-3T3 cell lines. Non-transformed, transformed BALB/c-3T3 cells,
      and tumor cell lines (obtained by injecting nude mice with transformed cell
      lines) were analyzed for genomic changes. DNAs from 10 different transformed
      clones and their corresponding tumor cell lines were amplified individually by
      RAPD analysis using 10 arbitrary primers. DNA from non-transformed BALB/c-3T3
      cells was used as a control to compare genetic alterations, if any, between non
      transformed, transformed and tumor cell populations. PCR products from RAPD were
      electrophoretically separated on agarose gels and the banding profiles were
      visualized by ethidium bromide staining. Five of the 10 primers tested revealed
      genomic changes in silica-transformed cell lines when compared to non-transformed
      BALB/c-3T3 cells. Comparison of all 10 transformed and tumor cell lines showed
      varied degrees of genomic changes using all 10 primers. CdCl2-transformed cell
      lines displayed fewer genomic changes, only three of 10 primers showed a positive
      result. CdCl2-transformed cells and their corresponding tumor cell lines showed
      specific banding pattern differences in six of the 10 samples tested with six of
      the 10 primers. Changes in band intensity were the most commonly observed changes
      both in silica- and CdCl2-transformed and tumor cell lines. The results seem to
      indicate a progressive change in genomic rearrangements which may directly or
      indirectly be associated with progression of tumorigenesis.

PMID- 10082923
TI  - Mutagenicities of N-nitrosodimethylamine and N-nitrosodiethylamine in Drosophila
      and their relationship to the levels of O-alkyl adducts in DNA.
AB  - N-Nitrosodialkylamines are potent carcinogens in experimental animals.
      Previously, we reported that the mutagenicity of N-nitrosodimethylamine (NDMA)
      was 10 times higher than that of N-nitrosodiethylamine (NDEA) in the Drosophila
      wing spot test. To find out how to explain this difference, we have measured the
      levels of O-alkylated bases in the DNA of exposed Drosophila larvae. Third instar
      larvae were fed for 3 or 6 h with NDMA or NDEA. Part of the treated larvae were
      grown to adult flies to score their wings for the presence of mutant spots. From
      the remaining larvae, DNA was isolated and digested to deoxyribonucleosides, and
      the digest fractionated by high-performance liquid chromatography (HPLC). The
      amounts of specific alkyldeoxyribonucleosides present in the fractions were
      quantified by a radioimmunoassay (RIA) using monoclonal antibodies. Dose
      dependent O6-methylguanine, O6-ethylguanine and O4-ethylthymine formations were
      found to be correlated with the induction frequencies of mutant wing spots. At
      the same exposure dose, the values of O6-alkylde- oxyguanosine/106 deoxyguanosine
      were similar for NDMA and NDEA: on feeding 20 micromol/1.5 ml feeding solution,
      the values for NDMA were 4.0 with 3 h and 18.5 with 6 h of exposure; with 20
      micromol NDEA, the corresponding values were 5.4 with 3 h and 14.6 with 6 h of
      exposure. The wing spot frequencies were very different; however, with NDMA, the
      total numbers of spots/wing were 3.5 (3 h) and 15 (6 h), and with NDEA 0.8 (3 h)
      and 0.9 (6 h). Similar discrepancies exist as well between the mutagenicities and
      the alkylation rates observed for O4-alkylthymidines. These results suggest that
      the difference between the mutagenic potencies of NDMA and NDEA cannot be
      explained by the amounts of O-alkyl adducts formed. Different mechanisms are
      considered by which NDMA and NDEA may produce the genetic effects observed.

PMID- 10082924
TI  - Frequency of spontaneous chromosome aberrations in mice: effects of age.
AB  - In this paper, we present data on chromosome aberration frequencies in mice which
      served as unexposed controls in a variety of radiation and chemical toxicology
      experiments conducted in our laboratory in recent years. All chromosome
      aberration data were obtained by chromosome painting. In peripheral blood
      lymphocytes from 102 animals, the frequencies of translocations and insertions
      increased significantly with age. No increase with age was seen for dicentrics or
      acentric fragments. When the data were analyzed by strain, the age-related
      increase in translocation frequencies was observed only in the 71 homozygous
      C57BL/6 mice and not in any of the three heterozygous strains. Very few
      aberrations of any type were observed in 62 bone marrow samples, and no effect of
      age was seen for any aberration type in this tissue. These results are similar to
      those observed in unexposed humans, and suggest that the increase in
      translocations is not the result of accumulated damage from chronic 'background'
      environmental exposures but instead may be due to biological processes associated
      with aging.

PMID- 10082925
TI  - Determining efficacy of cancer chemopreventive agents using a cell-free system
      concomitant with DNA adduction.
AB  - The large (>2000) and expanding number of natural and synthetic agents with
      potential cancer chemopreventive properties renders it economically and
      physically impossible to test each of these agents for their efficacy in the
      widely accepted 2-year animal bioassay and clinical trials. Therefore, there is a
      growing need for relevant short-term screening tests to study these compounds
      such that only the most efficacious ones undergo extensive long-term studies. We
      have previously reported in a pilot study that the use of a microsome-mediated
      test system concomitant with DNA adduction is a pertinent and relevant model for
      rapidly studying the efficacy and mechanisms of cancer chemopreventive agents. We
      have extended this study to investigate 26 additional agents for their potential
      chemopreventive abilities by studying their effects on microsome-mediated
      benzo[a]pyrene (BP)-DNA adduction. These agents had differential effects on the
      two major adducts of BP-DNA, i.e., BP-7,8-diol-9,10-epoxide (BPDE)-deoxyguanosine
      (dG) and 9-OH-BP-dG-derived adducts. These agents were therefore categorized into
      five classes. Three test agents (ellagic acid, genistein and oltipraz) were
      strong inhibitors of both adducts. These agents diminished BP-DNA adduction by 65
      95% and were categorized as Class I agents. Six other agents (benzyl isocyanate,
      R(+)-1-phenylethyl isocyanate, linoleic acid ethyl ester, (+)-biotin, indole-3
      carboxylic acid and beta-carotene) moderately inhibited both BP-DNA adducts (25
      64%); these compounds were identified as Class II agents. Six additional test
      agents inhibited only one adduct selectively and nine others were ineffective;
      these agents were categorized as Class III and Class IV, respectively.
      Interestingly, seven test agents enhanced BPDE-dG or 9-OH-BP-dG or both adducts
      and were categorized as Class V agents. Four of these Class V agents
      concomitantly inhibited BPDE-dG while enhancing 9-OH-BP-dG. This emphasizes the
      importance of studying individual DNA adducts in contrast to total DNA binding.
      In conclusion, Class I and Class II agents may be good candidates for further
      chemoprevention studies.

PMID- 10082926
TI  - Thalidomide and metabolites: indications of the absence of 'genotoxic'
      carcinogenic potentials.
AB  - Because of the reintroduction into human therapeutics of thalidomide, a
      recognized developmental toxicant in humans, there has been concern about its
      potential for inducing other health effects as well. The present study is
      concerned with the possible mutagenicity and carcinogenicity of this chemical.
      Using the expert system, META, a series of putative metabolites of thalidomide
      was generated. In addition to the known or hypothesized metabolites of
      thalidomide (N=12), a number of additional putative metabolites (N=131) were
      identified by META. The structures of these chemicals were subjected to structure
      activity analyses using predictive CASE/MULTICASE models of developmental
      toxicity, rodent carcinogenicity and mutagenicity in Salmonella. While
      thalidomide and some of its putative metabolites were predicted to be
      developmental toxicants, none of them were predicted to be rodent carcinogens.
      Putative metabolites containing the hydroxamic acid or hydroxylamine moieties
      were predicted to be mutagens. None of the 'known' metabolites of thalidomide
      contained these reactive moieties. Whether such intermediates are indeed
      generated or whether they are generated and are either unstable in the presence
      of oxygen or react rapidly with nucleophiles is unknown.

PMID- 10082927
TI  - Increased DNA single-strand break joining activity in UV-irradiated CD34+ versus
      CD34- bone marrow cells.
AB  - The kinetics of UV-irradiation-induced (254 nm) DNA single-strand breaks (SSBs)
      were studied in single human hematopoietic cells using alkaline comet assay.
      Three cell populations were investigated: (i) Bone marrow mononuclear cells
      (BMMNCs) isolated by density gradient centrifugation, (ii) CD34- cells, and (iii)
      CD34+ cells. The two latter populations were purified from BMMNCs by negative and
      positive selection, respectively, using anti-CD34 immunobeads. SSBs were induced
      faster by 10 and 50 J/m2 than by 2 J/m2 and those caused by 2 J/m2 were joined
      faster that those caused by 10 or 50 J/m2. During the first 1.5 h after
      irradiation with a dose of 10 J/m2, CD34+ cells joined SSBs faster than did
      BMMNCs. The superior joining capacity of CD34+ cells was further substantiated
      with a higher UV dose. The comet lengths, indicating the extent of DNA repair,
      among 8/8 study subjects were shorter in CD34+ than in CD34- cells when assessed
      24 h after a dose of 50 J/m2. Overall, the comet lengths at 24 h after
      irradiation were: CD34+ cells; 39+/-12 *m, and CD34- cells; 65+/-18 *m (8
      subjects, 50 cells measured from each donor, mean+/-S.D.; p=0.0087, Mann-Whitney
      U-test). These results strongly suggest that nucleotide excision repair, the
      major mechanism responsible for the repair of UV-irradiation-induced DNA lesions
      in mammalian cells, is increased in CD34+ cells compared with CD34- cells and
      with BMMNCs. These results may have implications in stem cell purging, clinical
      chemotherapy and carcinogenesis.

PMID- 10082928
TI  - Functional assessment of surface loops: deletion of eukaryote-specific peptide
      inserts in thymidylate synthase of Saccharomyces cerevisiae.
AB  - The primary structure is known for at least 29 thymidylate synthases and the
      crystal structure is known for several from both prokaryotes and eukaryotes. All
      these are markedly similar making thymidylate synthase one of the most highly
      conserved enzymes known. There are, however, two surface loops, one near the
      active site and the other near the dimer interface, which exist in distinctly
      prokaryotic and eukaryotic versions. Specifically, in eukaryotes these two
      surface loops have small peptide inserts conserved in size and partly conserved
      in sequence, that are not present in the prokaryotic thymidylate synthases. To
      address the possibility that these inserts provide eukaryote-specific functions
      the Saccharomyces cerevisiae loops were individually modified to mimic their
      prokaryotic counterparts. Altering the surface loop near the active site
      increased Km for the nucleotide substrate and decreased apparent Vmax. Mutant
      variants with alterations in the other surface loop were unable to dimerize.
      Therefore these surface loops have acquired, perhaps by way of the eukaryotic
      inserts, characteristics that are important for catalytic activity and quaternary
      structure respectively.

PMID- 10082929
TI  - Alcohol-induced biphasic inhibition of myosin subfragment 1 K-EDTA-ATPase.
AB  - Butanol-induced inhibition of K-EDTA-ATPase of myosin subfragment 1 proceeded by
      biphasic kinetics, consisting of rapid and slow inactivations. The extent of the
      rapid inactivation, which was estimated by extrapolating the process of slow
      inactivation to zero time of the incubation period, was saturated with butanol
      concentration. Recovery of activity by dilution in the rapid phase indicates that
      the rapid process is reversible. The slow inactivation was concomitant with a
      partial denaturation of the 50 kDa domain of S1, which was detected by limited
      tryptic digestion. Other alcohols (methanol, ethanol, propanol and hexanol) also
      inhibited the K-EDTA-ATPase in the rapid phase. The Ki decreased with an increase
      in the number of methylene groups of alcohol. When K-EDTA-ATPase activity in the
      rapid phase was plotted against viscosity, surface tension or dielectric
      constant, the curves were different for each of the various alcohol solutions.
      The rapid inactivation appears to be caused by a binding of the alkyl group to
      S1, rather than by solvent effects. The kinetics of rapid butanol inhibitions
      indicate that butanol reduces the maximum activity of ATPase but enhances an
      apparent affinity of S1 with ATP. These indications suggest that alcohol
      stabilizes S1.KATP intermediate. The rapid K-EDTA-ATPase inhibition was observed
      at the same alcohol concentration where S1 Mg-ATPase was activated.

PMID- 10082930
TI  - Structural and kinetic properties of adenylyl sulfate reductase from Catharanthus
      roseus cell cultures.
AB  - A cDNA encoding a plant-type APS reductase was isolated from an axenic cell
      suspension culture of Catharanthus roseus (Genbank/EMBL-databank accession number
      U63784). The open reading frame of 1392 bp (termed par) encoded for a protein
      (Mr=51394) consisting of a N-terminal transit peptide, a PAPS reductase-like core
      and a C-terminal extension with homology to the thioredoxin-like domain of
      protein disulfide isomerase. The APS reductase precursor was imported into pea
      chloroplasts in vitro and processed to give a mature protein of approximately 45
      kDa. The homologous protein from pea chloroplast stroma was detected using
      anti:par polyclonal antibodies. To investigate the catalytical function of the
      different domains deleted par proteins were purified. ParDelta1 lacking the
      transit sequence liberated sulfite from APS (Km 2.5+/-0.23 microM) in vitro with
      glutathione (Km 3+/-0.64 mM) as reductant (Vmax 2.6+/-0.14 U mg-1, molecular
      activity 126 min-1). ParDelta2 lacking the transit sequence and C-terminal domain
      had to be reconstituted with exogenous thioredoxin as reductant (Km 15. 3+/-1.27
      microM, Vmax 0.6+/-0.014 U mg-1). Glutaredoxin, GSH or DTT were ineffective
      substitutes. ParDelta1 (35.4%) and parDelta2 (21. 8%) both exhibited insulin
      reductase activity comparable to thioredoxin (100%). Protein disulfide isomerase
      activity was observed for parDelta1.

PMID- 10082931
TI  - Evidence for the existence of an unfolding intermediate state for aminoacylase
      during denaturation in guanidine solutions.
AB  - The equilibrium unfolding of pig kidney aminoacylase in guanidinium chloride
      (GdmCl) solutions was studied by following the fluorescence and circular
      dichroism (CD). At low concentrations of GdmCl, less than 1.0 M, the fluorescence
      intensity decreased with a slight red shift of the emission maximum (from 335 to
      340 nm). An unfolding intermediate was observed in low concentrations of
      denaturant (between 1.2 and 1.6 M GdmCl). This intermediate was characterized by
      a decreased fluorescence emission intensity, a red-shifted emission maximum, and
      increased binding of the fluorescence probe 1-anilino-8-naphthalenesulfonate. No
      significant changes of the secondary structure were indicated by CD measurement.
      This conformation state is similar to a molten globule state which may exist in
      the pathway of protein folding. Further changes in the fluorescence properties
      occurred at higher concentrations of GdmCl, more than 1.6 M, with a decrease in
      emission intensity and a significant red shift of the emission maximum from 340
      to 354 nm. In this stage, the secondary structure was completely broken. A study
      of apo-enzyme (Zn2+-free enzyme) produced similar results. However, comparison of
      the changes of the fluorescence emission spectra of native (Holo-) enzyme with
      Zn2+-free (Apo-) enzyme at low GdmCl concentrations showed that the structure of
      the Holo-enzyme was more stable than that of the Apo-enzyme.

PMID- 10082932
TI  - Halothane, an inhalational anesthetic agent, increases folding stability of serum
      albumin.
AB  - Inhalational anesthetic agents are known to alter protein function, but the
      nature of the interactions underlying these effects remains poorly understood. We
      have used differential scanning calorimetry to study the effects of the
      anesthetic agent halothane on the thermally induced unfolding transition of
      bovine serum albumin. We find that halothane (0.6-10 mM) stabilizes the folded
      state of this protein, increasing its transition midpoint temperature from 62 to
      71 degrees C. Binding of halothane to the native state of serum albumin thus
      outweighs any non-specific interactions between the thermally unfolded state of
      serum albumin and halothane in this concentration range. Based on the average
      enthalpy change DeltaH for unfolding of 170 kcal/mol, the increase from 62 to 71
      degrees C corresponds to an additional Gibbs energy of stabilization
      (DeltaDeltaG) due to halothane of more than 4 kcal/mol. Analysis of the
      dependence of DeltaDeltaG on halothane concentration shows that thermal unfolding
      of a bovine serum albumin molecule is linked to the dissociation of about one
      halothane molecule at lower halothane concentrations and about six at higher
      halothane concentrations. Serum albumin is the first protein that has been shown
      to be stabilized by an inhalational anesthetic.

PMID- 10082933
TI  - Characterization of aklavinone-11-hydroxylase from Streptomyces purpurascens.
AB  - Aklavinone-11-hydroxylase (RdmE) is a FAD monooxygenase participating in the
      biosynthesis of daunorubicin, doxorubicin and rhodomycins. The rdmE gene encodes
      an enzyme of 535 amino acids. The sequence of the Streptomyces purpurascens
      enzyme is similar to other Streptomyces aromatic polyketide hydroxylases. We
      overexpressed the gene in Streptomyces lividans and purified aklavinone-11
      hydroxylase to apparent homogeneity with four chromatographic steps utilizing a
      kinetic photometric enzyme assay. The enzyme is active as the monomer with a
      molecular mass of 60 kDa; it hydroxylates aklavinone and other anthracyclinones.
      Aklavinone-11-hydroxylase can use both NADH and NADPH as coenzyme but it is
      slowly inactivated in the presence of NADH. The apparent Km for NADPH is 2 mM and
      for aklavinone 10 microM. The enzyme is inactivated in the presence of
      phenylglyoxal and 2,3-butanedione. NADPH protects against inactivation of
      aklavinone-11-hydroxylase by phenylglyoxal.

PMID- 10082934
TI  - Cytochrome c' from Paracoccus denitrificans: spectroscopic studies consistent
      with a role for the protein in nitric oxide metabolism.
AB  - Cytochrome c' was purified from the denitrifying bacterium Paracoccus
      denitrificans and the interaction of the protein with nitric oxide was examined
      spectroscopically. Two distinct types of haem-nitrosyl electronic absorption
      spectrum were observed, which were dependent upon [NO]. When cytochrome c' was
      saturated with NO, alpha and beta bands were centred at 562 nm and 530 nm,
      whereas with sub-saturating concentrations of NO the alpha and beta bands were
      red-shifted to 578 nm and 542 nm respectively. Further spectroscopic analysis
      showed that purified cytochrome c', added to suspensions of P. denitrificans, is
      able to complex with the NO which is formed as a freely diffusible intermediate
      of denitrification. In the presence of added NO-3 or NO-2, 40-60% of Fe(II)
      cytochrome c' forms a 6-coordinate haem-nitrosyl complex. In the absence of
      nitrogen oxyanions or NO whole denitrifying cells are able to remove the NO from
      a Fe(II)-cytochrome c'-NO complex. These findings support the hypothesis that the
      physiological function of this enigmatic cytochrome involves the reversible
      binding of nitric oxide.

PMID- 10082935
TI  - The adsorption-induced secondary structure of beta-casein and of distinct parts
      of its sequence in relation to foam and emulsion properties.
AB  - Changes in the secondary structure upon adsorption of beta-casein (betaCN) and of
      distinct parts of its sequence were investigated by far-ultraviolet circular
      dichroism in order to find suggested relationships with foam and emulsion-forming
      and -stabilising properties of the same protein/peptides. A teflon/water
      interface was used as a model system for foam and emulsion interfaces. The
      maximum surface loads of beta-casein and its derived peptides were investigated.
      The main secondary structure element of all samples in solution was the unordered
      random coil, but upon adsorption ordered structure, especially alpha-helix, was
      induced. At lower pH more ordered structure was induced, just as at lower ionic
      strength. Apparently, both hydrophobic and hydrophilic groups influence the
      change of secondary structure induced at a hydrophobic interface. The results
      suggest that the hydrophobic C-terminal half of betaCN accounted for the high
      maximum surface load on teflon, while the N-terminal half of betaCN seemed to be
      responsible for the secondary structure induction upon adsorption. A relation
      between the maximum surface load and the foam-stabilising properties was found,
      but an influence of the secondary structure properties on the foam and emulsion
      forming and -stabilising properties was not observed.

PMID- 10082936
TI  - Melain G, a cysteine protease from green fruits of the bead tree, Melia
      azedarach: a protease affected by specific amino acids at P3 position.
AB  - A protease (melain G) was isolated from the greenish fruits of the bead tree,
      Melia azedarach var. japonica Makino. Melain G shares 110 identical amino acid
      residues (50%) with papain, 112 (51%) with actinidain, and 91 (41%) with stem
      bromelain. From the sites cleaved in the oxidized insulin B-chain and synthetic
      oligopeptide substrates by melain G, the enzyme preferred small amino acid
      residues such as Gly or Ser at the P2 position and negatively charged residues
      such as glutamic or cysteic acid at the P3 position. This is clearly different
      from the specificity of papain, which prefers the large hydrophobic amino acid
      residues such as Phe, Val, and Leu at the P2 position. Accordingly, it is
      presumed that the bottom of the S2 pocket of melain G is shallow due to the
      presence of a Phe residue, and a bulky P2 substrate (for example Phe residue) is
      not preferred by the enzyme. Negatively charged residues at the P3 position of
      substrates well suited the S3 site of melain G for making a salt bridge. It is
      likely that Arg61 is the S3 position of melain G by analogy with papain.

PMID- 10082937
TI  - Characterization of the consequence of a novel Glu-380 to Asp mutation by
      expression of functional P450c21 in Escherichia coli.
AB  - P450c21 catalyzes an important step in steroid synthesis. Its deficiency leads to
      symptoms of steroid imbalance. To obtain enough P450c21 for structure and
      function studies, we developed a method to express P450c21 in Escherichia coli.
      The 5'-region of the human P450c21 cDNA was modified to ensure efficient
      translation and the C terminus of the protein was extended with four His residues
      for easy purification. Mutant proteins with substitutions at residues 172 and 281
      exhibited decreased enzymatic activities similar to those found in mammalian
      cells. One new mutation changing Glu-380 to Asp (D380) caused 3-fold reduction in
      enzymatic activity. The amount of apoprotein production detected by
      immunoblotting and the affinity of the mutant protein towards substrate as
      measured by Km were normal. The defect lies in the decreased ability of the
      apoprotein to bind heme, which was measured by CO difference and substrate
      binding spectra. The D380 mutant protein had 3-fold reduction in peak heights in
      both spectra. This reduced heme binding resulted in 3-fold lower enzymatic
      activity.

PMID- 10082938
TI  - Purification of a 76-kDa iron-binding protein from human seminal plasma by
      affinity chromatography specific for ribonuclease: structural and functional
      identity with milk lactoferrin.
AB  - A pink-colored iron-binding protein has been found in large amount in human
      seminal plasma and identified as a lactoferrin isoform. Its purification, by a
      modification of a three-step chromatography procedure developed in an attempt to
      purify a ribonuclease from the same fluid, provided about 15-18 mg of pure
      protein from 100 ml of seminal plasma. Despite its ability to bind a ribonuclease
      ligand during the affinity step, the iron-binding protein did not display any
      detectable RNase activity in a standard assay with yeast RNA as substrate. It
      showed an apparent molecular weight of 76 kDa and resulted to be quite similar,
      if not identical, to human milk lactoferrin in many respects. Its N-terminal
      sequence (31 amino acid residues) starting with Arg-3 was identical to that of
      one of the N-terminally truncated lactoferrin variants isolated from human milk.
      Moreover, the amino acid sequence of a number of peptides, which represented
      about 23% of the entire sequence, has been also shown to be identical to that of
      the corresponding peptides of human milk lactoferrin. Double diffusion analysis
      revealed full recognition by antibodies anti-human milk lactoferrin of the human
      seminal plasma protein. Using immunoblotting analysis, both human milk
      lactoferrin and human seminal protein were recognized by antibodies anti-milk
      lactoferrin. When tested for its iron binding capacity, with Fe-NTA as iron
      donor, the protein purified was able to bind iron up to 100% saturation, as
      judged by absorbance at 465 nm.

PMID- 10082939
TI  - Characterization of a molten globule state of bovine carbonic anhydrase III: loss
      of asymmetrical environment of the aromatic residues has a profound effect on
      both the near- and far-UV CD spectrum.
AB  - Bovine muscle carbonic anhydrase (isoenzyme III; BCAIII) exhibited a three-state
      unfolding process at equilibrium upon denaturation in guanidine hydrochloride
      (GuHCl). The stable folding intermediate appeared to be of molten globule type.
      The stability towards GuHCl in terms of mid-point concentrations of denaturation
      were very similar for BCAIII and human CAII (HCAII). It was further demonstrated
      that the aromatic amino acid residues contributed significantly to the circular
      dichroism (CD) spectrum in the far-UV wavelength region during the native-
      >molten globule state transition. Thus, the ellipiticity change at 218 nm was
      shown to monitor the loss of tertiary interactions of aromatic side chains at the
      first unfolding transition as well as the rupture of secondary structure at the
      second unfolding transition. Similar aromatic contributions to the far-UV CD
      spectrum, but with varying magnitudes, were also noted for BCAII and HCAII,
      further emphasizing that interference of aromatic residues should not be
      neglected at wavelengths that normally are assigned to secondary structural
      changes.

PMID- 10082940
TI  - Relative affinities of poly(ADP-ribose) polymerase and DNA-dependent protein
      kinase for DNA strand interruptions.
AB  - Poly(ADP-ribose) polymerase (PARP) and DNA-dependent protein kinase (DNA-PK) are
      important nuclear enzymes that cooperate to minimize genomic damage caused by DNA
      strand interruptions. DNA strand interruptions trigger the ADP-ribosylation
      activity and phosphorylation activity of PARP and DNA-PK respectively. In order
      to understand the relationship of PARP and DNA-PK with respect to DNA binding
      required for their activation, we analyzed the kinetics of the reactions and
      determined the apparent dissociation constants (Kd app) of the enzymes for DNA
      strand interruptions. PARP has a high binding affinity for blunt ends of DNA (Kd
      app=116 pM) and 3' single-base overhangs (Kd app=332 pM) in comparison to long
      overhangs (Kd app=2.6-5.0 nM). Nicks are good activators of PARP although the
      affinity of PARP for nicks (Kd app=467 pM) is 4-fold less than that for blunt
      ends. The Kd app of DNA-PK for 3' single-base overhangs, blunt ends and long
      overhangs is 704 pM, 1.3 nM and 1.4-2.2 nM respectively. These results
      demonstrate that (1) PARP, when compared to DNA-PK, has a greater preference for
      blunt ends and 3' single-base overhangs but a weaker preference for long
      overhangs, and (2) nicks are effective in attracting and activating PARP. The
      possible implications of the preferences of PARP and DNA-PK for DNA strand
      interruptions in vivo are discussed.

PMID- 10082941
TI  - Inhibition of myosin ATPase by metal fluoride complexes.
AB  - Magnesium (Mg2+) is the physiological divalent cation stabilizing nucleotide or
      nucleotide analog in the active site of myosin subfragment 1 (S1). In the
      presence of fluoride, Mg2+ and MgADP form a complex that traps the active site of
      S1 and inhibits myosin ATPase. The ATPase inactivation rate of the magnesium
      trapped S1 is comparable but smaller than the other known gamma-phosphate analogs
      at 1.2 M-1 s-1 with 1 mM MgCl2. The observed molar ratio of Mg/S1 in this complex
      of 1.58 suggests that magnesium occupies the gamma-phosphate position in the ATP
      binding site of S1 (S1-MgADP-MgFx). The stability of S1-MgADP-MgFx at 4 degrees C
      was studied by EDTA chase experiments but decomposition was not observed.
      However, removal of excess fluoride causes full recovery of the K+-EDTA ATPase
      activity indicating that free fluoride is necessary for maintaining a stable trap
      and suggesting that the magnesium fluoride complex is bonded to the bridging
      oxygen of beta-phosphate more loosely than the other known phosphate analogs. The
      structure of S1 in S1-MgADP-MgFx was studied with near ultraviolet circular
      dichroism, total tryptophan fluorescence, and tryptophan residue 510 quenching
      measurements. These data suggest that S1-MgADP-MgFx resembles the M**.ADP.Pi
      steady-state intermediate of myosin ATPase. Gallium fluoride was found to compete
      with MgFx for the gamma-phosphate site in S1-MgADP-MgFx. The ionic radius and
      coordination geometry of magnesium, gallium and other known gamma-phosphate
      analogs were compared and identified as important in determining which myosin
      ATPase intermediate the analog mimics.

PMID- 10082942
TI  - Degradation of protein kinase Malpha by mu-calpain in a mu-calpain-protein kinase
      Calpha complex.
AB  - In previous studies, we isolated and identified a mu-calpain-PKCalpha complex
      from rabbit skeletal muscle. At the same time we pointed out that an association
      between mu-calpain and PKCalpha could occur at the level of the plasma membrane
      of muscle cells, and that PKCalpha could thus be considered as a potential mu
      calpain substrate. In the present study, using the mu-calpain-PKCalpha complex as
      a model, we report that mu-calpain is activated in the combined presence of
      physiological calcium concentrations (less than 1 microM) and phosphatidylserine.
      Furthermore our data also show that: (1) there exists a correlation between the
      appearance of autolyzed mu-calpain forms and PKCalpha hydrolysis which leads to
      the formation of PKMalpha; (2) in certain experimental conditions, autolyzed mu
      calpain forms are able to hydrolyze PKMalpha independently of the presence of
      diacylglycerol.

PMID- 10082943
TI  - N-dansyl-S-nitrosohomocysteine a fluorescent probe for intracellular thiols and S
      nitrosothiols.
AB  - The fluorescence emission spectrum of N-dansyl-S-nitrosohomocysteine was enhanced
      approximately 8-fold upon removal of the NO group either by photolysis or by
      transnitrosation with free thiols like glutathione. The fluorescence enhancement
      was reversible in that it could be quenched in the presence of excess S
      nitrosoglutathione. Attempts were then made to utilize N-dansyl-S
      nitrosohomocysteine as an intracellular probe of thiols/S-nitrosothiols.
      Fluorescence microscopy of fibroblasts in culture indicated that intracellular N
      dansyl-S-nitrosohomocysteine levels reached a maximum within 5 min. N-Dansyl-S
      nitrosohomocysteine fluorescence was directly proportional to intracellular GSH
      levels, directly determined with HPLC. N-Dansyl-S-nitrosohomocysteine preloaded
      cells were also sensitive to S-nitrosoglutathione uptake as the intracellular
      fluorescence decreased as a function of time upon exposure to extracellular S
      nitrosoglutathione.

PMID- 10082945
TI  - Thyroglobulin, the prothyroid hormone: chemistry, synthesis and degradation.

PMID- 10082946
TI  - Interaction between leukocyte elastase and elastin: quantitative and catalytic
      analyses.
AB  - Solubilization of elastin by human leukocyte elastase (HLE) cannot be analyzed by
      conventional kinetic methods because the biologically relevant substrate is
      insoluble and the concentration of enzyme-substrate complex has no physical
      meaning. We now report quantitative measurements of the binding and catalytic
      interaction between HLE and elastin permitted by analogy to receptor-ligand
      systems. Our results indicated that a limited and relatively constant number of
      enzyme binding sites were available on elastin, and that new sites became
      accessible as catalysis proceeded. The activation energies and solvent deuterium
      isotope effects were similar for catalysis of elastin and a soluble peptide
      substrate by HLE, yet the turnover number for HLE digestion of elastin was 200
      2000-fold lower than that of HLE acting on soluble peptide substrates. Analysis
      of the binding of HLE to elastin at 0 degrees C, in the absence of significant
      catalytic activity, demonstrated two classes of binding sites (Kd=9.3x10(-9) M
      and 2.5x10(-7) M). The higher affinity sites accounted for only 6% of the total
      HLE binding capacity, but essentially all of the catalytic activity, and
      dissociation of HLE from these sites was minimal. Our studies suggest that
      interaction of HLE with elastin in vivo may be very persistent and permit
      progressive solubilization of this structurally important extracellular matrix
      component.

PMID- 10082947
TI  - Cloning, expression, and characterization of the Fab fragment of the anti
      lysozyme antibody HyHEL-5.
AB  - Hybridoma cDNAs encoding the individual chains of the Fab fragment of the well
      characterized murine monoclonal antibody HyHEL-5 were cloned and sequenced. The
      recombinant Fab fragment was produced by expressing each chain in a separate
      Escherichia coli pET vector, denaturing inclusion bodies and co-refolding.
      Characterization of the purified Fab by MALDI-TOF mass spectrometry and N
      terminal amino acid sequencing demonstrated proper processing of the individual
      chains. The association of the recombinant Fab fragment with hen egg lysozyme and
      the avian epitope variant bobwhite quail lysozyme was found by isothermal
      titration calorimetry to have energetics very similar to that of the HyHEL-5 IgG.
      Heterologous expression of the HyHEL-5 Fab fragment opens the way to
      structure/function studies in this well-known system.

PMID- 10082948
TI  - Q-Band resonance Raman investigation of turnip cytochrome f and Rhodobacter
      capsulatus cytochrome c1.
AB  - The results of a comprehensive Q-band resonance Raman investigation of cytochrome
      c1 and cytochrome f subunits of bc1 and b6f complexes are presented. Q-band
      excitation provides a particularly effective probe of the local heme environments
      of these species. The effects of protein conformation (particularly axial
      ligation) on heme structure and function were further investigated by comparison
      of spectra obtained from native subunits to those of a site directed c1 mutant
      (M183L) and various pH-dependent species of horse heart cytochrome c. In general,
      all species examined displayed variability in their axial amino acid ligation
      that suggests a good deal of flexibility in their hemepocket conformations.
      Surprisingly, the large scale protein rearrangements that accompany axial ligand
      replacement have little or no effect on macrocycle geometry in these species.
      This indicates the identity and/or conformation of the peptide linkage between
      the two cysteines that are covalently linked to the heme periphery may determine
      heme geometry.

PMID- 10082949
TI  - Ca2+-dependent interaction of the inhibitory region of troponin I with acidic
      residues in the N-terminal domain of troponin C.
AB  - Ca2+ regulation of vertebrate striated muscle contraction is initiated by
      conformational changes in the N-terminal, regulatory domain of the Ca2+-binding
      protein troponin C (TnC), altering the interaction of TnC with the other subunits
      of troponin complex, TnI and TnT. We have investigated the role of acidic amino
      acid residues in the N-terminal, regulatory domain of TnC in binding to the
      inhibitory region (residues 96-116) of TnI. We constructed three double mutants
      of TnC (E53A/E54A, E60A/E61A and E85A/D86A), in which pairs of acidic amino acid
      residues were replaced by neutral alanines, and measured their affinities for
      synthetic inhibitory peptides. These peptides had the same amino acid sequence as
      TnI segments 95-116, 95-119 or 95-124, except that the natural Phe-100 of TnI was
      replaced by a tryptophan residue. Significant Ca2+-dependent increases in the
      affinities of the two longer peptides, but not the shortest one, to TnC could be
      detected by changes in Trp fluorescence. In the presence of Ca2+, all the mutant
      TnCs showed about the same affinity as wild-type TnC for the inhibitory peptides.
      In the presence of Mg2+ and EGTA, the N-terminal, regulatory Ca2+-binding sites
      of TnC are unoccupied. Under these conditions, the affinity of TnC(E85A/D86A) for
      inhibitory peptides was about half that of wild-type TnC, while the other two
      mutants had about the same affinity. These results imply a Ca2+-dependent change
      in the interaction of TnC Glu-85 and/or Asp-86 with residues (117-124) on the C
      terminal side of the inhibitory region of TnI. Since Glu-85 and/or Asp-86 of TnC
      have also been demonstrated to be involved in Ca2+-dependent regulation through
      interaction with TnT, this region of TnC must be critical for troponin function.

PMID- 10082950
TI  - Isolation of plaice (Pleuronectes platessa) alpha1-microglobulin: conservation of
      structure and chromophore.
AB  - A cDNA coding for plaice (Pleuronectes platessa) alpha1-microglobulin (Leaver et
      al., 1994, Comp. Biochem. Physiol. 108B, 275-281) was expressed and purified from
      baculovirus-infected insect cells. Specific monoclonal antibodies were then
      prepared and used to isolate the protein from plaice liver and serum. Mature 28.5
      kDa alpha1-microglobulin was found in both liver and serum. The protein consisted
      of an 184 amino acid peptide with a complex N-glycan in position Asn123, one
      intrachain disulfide bridge and a yellow-brown chromophore. Physicochemical
      characterization indicated a globular shape with a frictional ratio of 1.37,
      electrophoretic charge-heterogeneity and antiparallel beta-sheet structure. A
      smaller, incompletely glycosylated, yellow-brown alpha1-microglobulin as well as
      a 45 kDa precursor protein were also found in liver. The chromophore was found to
      be linked to alpha1-microglobulin intracellularly. Recombinant plaice alpha1
      microglobulin isolated from insect cells had the same N-terminal sequence,
      globular shape and yellow-brown color as mature alpha1-microglobulin, but carried
      a smaller, fucosylated, non-sialylated N-glycan in the Asn123 position. The
      concentration of alpha1-microglobulin in plaice serum was 20 mg/l and it was
      found both as a 28.5 kDa component and as high molecular weight components. Thus,
      the size, shape, charge and color of plaice alpha1-microglobulin were similar to
      mammalian alpha1-microglobulin, indicating a high degree of structural
      conservation between fish and human alpha1-microglobulin. The monoclonal
      antibodies against plaice alpha1-microglobulin cross-reacted with human alpha1
      microglobulin, emphasizing the structural similarity.

PMID- 10082951
TI  - A 20-kDa domain is required for phosphatidic acid-induced allosteric activation
      of phospholipase D from Streptomyces chromofuscus.
AB  - Two phospholipase D (PLD) enzymes with both hydrolase and transferase activities
      were isolated from Streptomyces chromofuscus. There were substantial differences
      in the kinetic properties of the two PLD enzymes towards monomeric, micellar, and
      vesicle substrates. The most striking difference was that the higher molecular
      weight enzyme (PLD57 approximately 57 kDa) could be activated allosterically with
      a low mole fraction of phosphatidic acid (PA) incorporated into a PC bilayer
      (Geng et al., J. Biol. Chem. 273 (1998) 12195-12202). PLD42/20, a tightly
      associated complex of two peptides, one of 42 kDa and the other 20 kDa, had a 4-6
      fold higher Vmax toward PC substrates than PLD57 and was not activated by PA. N
      Terminal sequencing of both enzymes indicated that both components of PLD42/20
      were cleavage products of PLD57. The larger component included the N-terminal
      segment of PLD57 and contained the active site. The N-terminus of the smaller
      peptide corresponded to the C-terminal region of PLD57; this peptide had no PLD
      activity by itself. Increasing the pH of PLD42/20 to 8.9, followed by
      chromatography of PLD42/20 on a HiTrap Q column at pH 8.5 separated the 42- and
      20-kDa proteins. The 42-kDa complex had about the same specific activity with or
      without the 20-kDa fragment. The lack of PA activation for the 42-kDa protein and
      for PLD42/20 indicates that an intact C-terminal region of PLD57 is necessary for
      activation by PA. Furthermore, the mechanism for transmission of the allosteric
      signal requires an intact PLD57.

PMID- 10082952
TI  - Towards the reaction mechanism of pyrogallol-phloroglucinol transhydroxylase of
      Pelobacter acidigallici.
AB  - Conversion of pyrogallol to phloroglucinol was studied with the molybdenum enzyme
      transhydroxylase of the strictly anaerobic fermenting bacterium Pelobacter
      acidigallici. Transhydroxylation experiments in H218O revealed that none of the
      hydroxyl groups of phloroglucinol was derived from water, confirming the concept
      that this enzyme transfers a hydroxyl group from the cosubstrate 1,2,3, 5
      tetrahydroxybenzene (tetrahydroxybenzene) to the acceptor pyrogallol, and
      simultaneously regenerates the cosubstrate. This concept requires a reaction
      which synthesizes the cofactor de novo to maintain a sufficiently high
      intracellular pool during growth. Some sulfoxides and aromatic N-oxides were
      found to act as hydroxyl donors to convert pyrogallol to tetrahydroxybenzene.
      Again, water was not the source of the added hydroxyl groups; the oxides reacted
      as cosubstrates in a transhydroxylation reaction rather than as true oxidants in
      a net hydroxylation reaction. No oxidizing agent was found that supported a
      formation of tetrahydroxybenzene via a net hydroxylation of pyrogallol. However,
      conversion of pyrogallol to phloroglucinol in the absence of tetrahydroxybenzene
      was achieved if little pyrogallol and a high amount of enzyme preparation was
      used which had been pre-exposed to air. Obviously, the enzyme was oxidized by air
      to form sufficient amounts of tetrahydroxybenzene from pyrogallol to start the
      reaction. A reaction mechanism is proposed which combines an oxidative
      hydroxylation with a reductive dehydroxylation via the molybdenum cofactor, and
      allows the transfer of a hydroxyl group between tetrahydroxybenzene and
      pyrogallol without involvement of water. With this, the transhydroxylase differs
      basically from all other hydroxylating molybdenum enzymes which all use water as
      hydroxyl source.

PMID- 10082953
TI  - Hydrostatic pressure and calcium-induced dissociation of calpains.
AB  - The dissociation of mu- and m-calpains was studied by fluorescence spectroscopy
      under high hydrostatic pressure (up to 650 MPa). Increasing pressure induced a
      red shift of the tryptophan fluorescence of the calcium-free enzyme. The
      concentration dependence of the spectral transition was consistent with a
      pressure-induced dissociation of the subunits. Rising temperature increased the
      stability of calpain heterodimers and confirmed the predominance of hydrophobic
      interactions between monomers. At saturating calcium, the spectral transition was
      not observed for native or iodoacetamide-inactivated calpains, indicating that
      they were already dissociated by calcium. The reaction volume was about -150 ml
      mol-1 for both isoforms, and the dissociation constants at atmospheric pressure
      are approximately 10-12 M and 10-15 M for mu- and m-calpains, respectively. This
      result indicates a tighter interaction in the isoform that requires higher
      calcium concentration for activity.

PMID- 10082954
TI  - A new antifungal peptide from the seeds of Phytolacca americana:
      characterization, amino acid sequence and cDNA cloning.
AB  - An antifungal peptide from seeds of Phytolacca americana, designated PAFP-s, has
      been isolated. The peptide is highly basic and consists of 38 residues with three
      disulfide bridges. Its molecular mass of 3929.0 was determined by mass
      spectrometry. The complete amino acid sequence was obtained from automated Edman
      degradation, and cDNA cloning was successfully performed by 3'-RACE. The deduced
      amino acid sequence of a partial cDNA corresponded to the amino acid sequence
      from chemical sequencing. PAFP-s exhibited a broad spectrum of antifungal
      activity, and its activities differed among various fungi. PAFP-s displayed no
      inhibitory activity towards Escherichia coli. PAFP-s shows significant sequence
      similarities and the same cysteine motif with Mj-AMPs, antimicrobial peptides
      from seeds of Mirabilis jalapa belonging to the knottin-type antimicrobial
      peptide.

PMID- 10082955
TI  - Thermodynamic studies on anion binding to apotransferrin and to recombinant
      transferrin N-lobe half molecules.
AB  - Equilibrium constants for the binding of anions to apotransferrin, to the
      recombinant N-lobe half transferrin molecule (Tf/2N), and to a series of mutants
      of Tf/2N have been determined by difference UV titrations of samples in 0.1 M
      Hepes buffer at pH 7.4 and 25 degrees C. The anions included in this study are
      phosphate, sulfate, bicarbonate, pyrophosphate, methylenediphosphonic acid, and
      ethylenediphosphonic acid. There are no significant differences between anion
      binding to Tf/2N and anion binding to the N-lobe of apotransferrin. The binding
      of simple anions like phosphate appears to be essentially equivalent for the two
      apotransferrin binding sites. The binding of pyrophosphate and the diphosphonates
      is inequivalent, and the studies on the recombinant Tf/2N show that the stronger
      binding is associated with the N-terminal site. Anion binding constants for
      phosphate, pyrophosphate, and the diphosphonates with the N-lobe mutants K206A,
      K296A, and R124A have been determined. Anion binding tends to be weakest for the
      K296A mutant, but the variation in log K values among the three mutants is
      surprisingly small. It appears that the side chains of K206, K296, and R124 all
      make comparable contributions to anion binding. There are significant variations
      in the intensities of the peaks in the difference UV spectra that are generated
      by the titrations of the mutant apoproteins with these anions. These differences
      appear to be related more to variations in the molar extinction coefficients of
      the anion-protein complexes rather than to differences in binding constants.

PMID- 10082956
TI  - Molecular cloning and primary structure analysis of porcine pancreatic alpha
      amylase.
AB  - A cDNA library was constructed in a Uni-ZAP XR vector using mRNA isolated from
      porcine pancreas. A full-length alpha-amylase cDNA was obtained using a
      combination of library screening and nested polymerase chain reaction. Sequencing
      of the clone revealed a 1536-nucleotide (nt) open reading frame encoding a
      protein of 496 amino acid (aa) residues with a signal peptide of 15 aa. The
      calculated molecular mass of the enzyme was 55354 Da, in accordance with those of
      the purified porcine pancreatic alpha-amylase forms (PPAI and PPAII) as
      determined by mass spectrometry. A comparison of the deduced aa sequence with
      published peptidic sequences of PPAI identified a number of mismatches. The
      sequence of the cDNA reported here provides a sequence reference for PPA in
      excellent agreement with the refined three-dimensional structures of both PPAI
      and PPAII. No evidence for a second variant was found in the cDNA library and it
      is most likely that PPAI and PPAII are two forms of the same protein. The primary
      structure of PPA shows high homology with human, mouse and rat pancreatic alpha
      amylases. The 304-310 region, corresponding to a mobile loop involved in
      substrate binding and processing near the active site, is fully conserved.

PMID- 10082957
TI  - Systematic mutations of highly conserved His49 and carboxyl-terminal of
      recombinant porcine liver NADH-cytochrome b5 reductase solubilized domain.
AB  - The cDNA encoding solubilized porcine liver NADH-cytochrome b5 reductase
      catalytic domain (Pb5R) was cloned and overexpressed in Escherichia coli. A
      highly conserved His49 and a C-terminal Phe272 of Pb5R, which are located near
      the isoalloxazine moiety of the FAD, were systematically modulated by site
      directed mutagenesis. Large structural change was not detected on the absorption
      and circular dichroism spectra of mutant proteins. Drastic changes in enzymatic
      properties were not observed, but the apparent Km value for soluble form of
      porcine liver cytochrome b5 (Pb5) was affected by the substitutions of His49 with
      glutamic acid and with lysine, deletion of C-terminal Phe272, and addition of
      Gly273. The values of the catalytic constant (kcat) were obviously decreased by
      the substitution of His49 with glutamic acid or the addition of Gly273. In these
      two mutants, the rate for reduction of FAD was decreased, and the rate for
      autoxidation of reduced FAD was increased. These results showed that His49 and C
      terminal carboxyl group in Pb5R are not critical for the electron transfer to
      Pb5, but the electrostatic environmental changes at these positions could affect
      the recognition of Pb5 and modulate the catalytic function of the enzyme by
      changing the stability of reduced FAD.

PMID- 10082958
TI  - Kinetics and mechanism of exchange of apolipoprotein C-III molecules from very
      low density lipoprotein particles.
AB  - Transfer of apolipoprotein (apo) molecules between lipoprotein particles is an
      important factor in modulating the metabolism of the particles. Although the
      phenomenon is well established, the kinetics and molecular mechanism of passive
      apo exchange/transfer have not been defined in detail. In this study, the kinetic
      parameters governing the movement of radiolabeled apoC molecules from human very
      low density lipoprotein (VLDL) to high density lipoprotein (HDL3) particles were
      measured using a manganese phosphate precipitation assay to rapidly separate the
      two types of lipoprotein particles. In the case of VLDL labeled with human
      [14C]apoCIII1, a large fraction of the apoCIII1 transfers to HDL3 within 1 minute
      of mixing the two lipoproteins at either 4 degrees or 37 degrees C. As the
      diameter of the VLDL donor particles is decreased from 42-59 to 23-25 nm, the
      size of this rapidly transferring apoCIII1 pool increases from about 50% to 85%.
      There is also a pool of apoCIII1 existing on the donor VLDL particles that
      transfers more slowly. This slow transfer follows a monoexponential rate
      equation; for 35-40 nm donor VLDL particles the pool size is approximately 20%
      and the t1/2 is approximately 3 h. The flux of apoCIII molecules between VLDL and
      HDL3 is bidirectional and all of the apoCIII seems to be available for exchange
      so that equilibrium is attained. It is likely that the two kinetic pools of
      apoCIII are related to conformational variations of individual apo molecules on
      the surface of VLDL particles. The rate of slow transfer of apoCIII1 from donor
      VLDL (35-40 nm) to acceptor HDL3 is unaffected by an increase in the acceptor to
      donor ratio, indicating that the transfer is not dependent on collisions between
      donor and acceptor particles. Consistent with this, apoCIII1 molecules can
      transfer from donor VLDL to acceptor HDL3 particles across a 50 kDa molecular
      mass cutoff semipermeable membrane separating the lipoprotein particles. These
      results indicate that apoC molecules transfer between VLDL and HDL3 particles by
      an aqueous diffusion mechanism.

PMID- 10082959
TI  - Thermodynamic and kinetic aspects on water vs. organic solvent as reaction media
      in the enzyme-catalysed reduction of ketones.
AB  - The stereoselective reduction of ketones catalysed by alcohol dehydrogenase from
      Thermoanaerobium brockii was studied in different reaction media, hexane at
      controlled water activities, hexane with 2. 5% water (biphasic) and pure water.
      The reactions were studied in the temperature range from -1 to 50 degrees C.
      Increasing the water activity from 0.53 to 0.97 increased the reaction rate 16
      fold. The rate was further enhanced in hexane when exceeding the water solubility
      and in pure water the rates were even higher. This was general for all ketones
      studied. At controlled water activity the entropy of activation (DeltaSdouble
      dagger) was the dominating factor. Large negative DeltaSdouble dagger values
      caused low reaction rates at low aw. When increasing the carbon chain length of
      the substrate, for reactions in hexane, the decrease of reaction rate was mainly
      due to a decrease in DeltaSdouble dagger. In the comparison between hexane and
      pure water, DeltaGdouble dagger values were higher in hexane due to higher
      DeltaHdouble dagger (activation enthalpy) values. The enantioselectivity (E
      value) increased from 2.6 at water activity 0. 53 to 4.6 at water activity 0.97.
      Changing media from hexane (2.5%, v/v water) to pure water was not affecting the
      enantioselectivity or the specificity for different ketones.

PMID- 10082960
TI  - Electric birefringence of recombinant spectrin segments 14, 14-15, 14-16, and 14
      17 from Drosophila alpha-spectrin.
AB  - Members of the spectrin protein family can be found in many different cells and
      organisms. In all cases studied, the major functional role of these proteins is
      believed to be structural rather than enzymatic. All spectrin proteins are highly
      elongated and consist mainly of homologous repeats that constitute rigid segments
      connected in tandem. It is commonly believed that the details of the spectrin
      function depend critically on the flexibility of the links between the segments.
      Here we report on a work addressing this question by studying the transient
      electric birefringence of recombinant spectrin fragments consisting of segments
      14, 14-15, 14-16, and 14-17, respectively, from Drosophila alpha-spectrin.
      Transient electric birefringence depends sharply on both molecular length and
      flexibility. We found that the birefringence relaxation time of segment 14
      measured at 4 degrees C, but scaled to what is expected at 20 degrees C, equals
      16 ns (+/-15%) at pH 7.5 and ionic strength 6 mM. This is consistent with this
      single segment being rigid, 5 nm long and having an axial ratio equal to about
      two. Under the same conditions, segments 14-15, 14-16 and 14-17 show relaxation
      times of 45, 39 and 164 ns (all +/-20%), respectively, scaled to what is expected
      at 20 degrees C. When the temperature is increased to 37 degrees C the main
      relaxation time for each of these multisegment fragments, scaled to what is
      expected at 20 degrees C, increased to 46, 80, and 229 ns (all +/-20%),
      respectively. When the ionic strength and the Debye shielding is low, the
      dynamics of these short fragments even at physiological temperature is nearly the
      same as for fully extended weakly bending rods with the same lengths and axial
      ratios. When the ionic strength is increased to 85 mM, the main relaxation time
      for each of these multisegment fragments is reduced 20-50% which suggests that at
      physiological salt and temperature conditions the links in 2-4-segment-long
      fragments exhibit significant thermally induced flexing. Provided that the
      recombinant spectrin fragments can serve as a model for native spectrin, this
      implies that, at physiological conditions, the overall conformational dynamics of
      a native spectrin protein containing 20-40 segments equals that of a flexible
      polymer.

PMID- 10082961
TI  - Coupling of the peroxidase and cyclooxygenase reactions of prostaglandin H
      synthase.
AB  - Interrelations between peroxidase and cyclooxygenase reactions catalyzed by
      prostaglandin endoperoxide synthase (prostaglandin H synthase) were analyzed in
      terms of the mutual influence of these reactions. The original branched-chain
      mechanism predicts competition between these two reactions for enzyme, so that
      peroxidase cosubstrate should inhibit the cyclooxygenase reaction and the
      cyclooxygenase substrate is expected to inhibit the peroxidase reaction. In stark
      contrast, the peroxidase reducing substrate is well known to strongly stimulate
      the cyclooxygenase reaction. In the present work the opposite effect, the
      influence of the cyclooxygenase substrate on the peroxidase reaction was studied.
      Experiments were conducted on the effect of arachidonic acid on the consumption
      of p-coumaric acid by prostaglandin H synthase and 5-phenyl-4-pentenyl-1
      hydroperoxide. Neither the steady-state rates nor the total extent of p-coumaric
      acid consumption was affected by the addition of arachidonic acid. This suggests
      that the cyclooxygenase substrate does not influence observable velocities of the
      peroxidase reaction, namely oxidation and regeneration of the resting enzyme. The
      data support coupling of the cyclooxygenase and peroxidase reactions. A
      combination of the branched-chain and tightly coupled mechanisms is proposed,
      which includes a tyrosyl radical active enzyme intermediate regenerated through
      the peroxidase cycle. Numerical integration of the proposed reaction scheme
      agrees with the observed relations between peroxidase and cyclooxygenase
      reactions in the steady state.

PMID- 10082962
TI  - Electron paramagnetic resonance reveals altered topography of the active center
      gorge of acetylcholinesterase after binding of fasciculin to the peripheral site.
AB  - Fasciculin, a peptidic toxin from snake venom, inhibits mammalian and fish
      acetylcholinesterases (AChE) by binding to the peripheral site of the enzyme.
      This site is located at the rim of a narrow, deep gorge which leads to the active
      center triad, located at its base. The proposed mechanisms for AChE inhibition by
      fasciculin include allosteric events resulting in altered conformation of the
      AChE active center gorge. However, a fasciculin-induced altered topography of the
      active center gorge has not been directly demonstrated. Using electron
      paramagnetic resonance with the spin-labeled organophosphate 1-oxyl-2,2,6, 6
      tetramethyl-4-piperidinylethylphosphorofluoridate (EtOSL) specifically bound to
      the catalytic serine of mouse AChE (mAChE), we show that bound fasciculin on
      mAChE slows down, but does not prevent phosphorylation of the active site serine
      by EtOSL and protects the gorge conformation against thermal denaturation. Most
      importantly, a restricted freedom of motion of the spin label bound to the
      fasciculin-associated mAChE, compared to mAChE, is evidenced. Molecular models of
      mAChE and fasciculin-associated mAChE with tethered EtOSL enantiomers indicate
      that this restricted motion is due to greater proximity of the S-EtOSL nitroxide
      radical to the W86 residue in the fasciculin-associated enzyme. Our results
      demonstrate a topographical alteration indicative of a restricted conformation of
      the active center gorge of mAChE with bound fasciculin at its rim.

PMID- 10082963
TI  - Small angle X-ray scattering of wheat seed-storage proteins: alpha-, gamma- and
      omega-gliadins and the high molecular weight (HMW) subunits of glutenin.
AB  - Small angle X-ray scattering in solution was performed on seed-storage proteins
      from wheat. Three different groups of gliadins (alpha-, gamma- and omega-) and a
      high molecular weight (HMW) subunit of glutenin (1Bx20) were studied to determine
      molecular size parameters. All the gliadins could be modelled as prolate
      ellipsoids with extended conformations. The HMW subunit existed as a highly
      extended rod-like particle in solution with a length of about 69 nm and a
      diameter of about 6.4 nm. Specific aggregation effects were observed which may
      reflect mechanisms of self-assembly that contribute to the unique viscoelastic
      properties of wheat dough.

PMID- 10082964
TI  - Molecular characterization and crystallization of Diocleinae lectins.
AB  - Molecular characterization of seven Diocleinae lectins was assessed by sequence
      analysis, determination of molecular masses by mass spectrometry, and analytical
      ultracentrifugation equilibrium sedimentation. The lectins show distinct pH
      dependent dimer-tetramer equilibria, which we hypothesize are due to small
      primary structure differences at key positions. Lectins from Dioclea guianensis,
      Dioclea virgata, and Cratylia floribunda seeds have been crystallized and
      preliminary X-ray diffraction analyses are reported.

PMID- 10082965
TI  - Purification and characterization of a serine protease with fibrinolytic activity
      from Tenodera sinensis (praying mantis).
AB  - Mantis egg fibrolase (MEF) was purified from the egg cases of Tenodera sinensis
      using ammonium sulfate fractionation, gel filtration on Bio-Gel P-60 and affinity
      chromatography on DEAE Affi-Gel blue gel. The protease was assessed homogeneous
      by SDS-polyacrylamide gel electrophoresis and has a molecular mass of 31500 Da.
      An isoelectric point of 6.1 was determined by isoelectric focusing. Amino acid
      sequencing of the N-terminal region established a primary structure composed of
      Ala-Asp-Val-Val-Gln-Gly-Asp-Ala-Pro-Ser. MEF readily digested the Aalpha- and
      Bbeta-chains of fibrinogen and more slowly the gamma-chain. The nonspecific
      action of the enzyme results in extensive hydrolysis of fibrinogen and fibrin
      releasing a variety of fibrinopeptide. The enzyme is inactivated by Cu2+ and Zn2+
      and inhibited by PMSF and chymostatin, yet elastinal, aprotinin, TLCK, TPCK,
      EDTA, EGTA, cysteine, beta-mercaptoethanol, iodoacetate, E64, benzamidine and
      soybean trypsin inhibitor do not affect activity. Antiplasmin was not sensitive
      to MEF but antithrombin III inhibited the enzymatic activity of MEF. Among
      chromogenic protease substrates, the most sensitive to MEF hydrolysis was benzoyl
      Phe-Val-Arg-p-nitroanilide with maximal activity at pH 7.0 and 30 degrees C. MEF
      preferentially cleaved the oxidized B-chain of insulin between Leu15 and Tyr16. D
      Dimer concentrations increased on incubation of cross-linked fibrin with MEF,
      indicating the enzyme has a strong fibrinolytic activity.

PMID- 10082966
TI  - Pteridines as inhibitors of xanthine oxidase: structural requirements.
AB  - Different pteridine derivatives were investigated for their inhibitory action on
      xanthine oxidase. From 27 investigated compounds, 13 showed concentration
      dependent inhibition of the enzyme. Concentrations necessary for 50% inhibition
      ranged from <0.1 up to >100 microM. Different types of inhibition were found
      concerning xanthine and pterin as substrates: competitive, noncompetitive and
      mixed type. Out of 18 aromatic compounds tested, 12 were inhibitors. Only one out
      of nine reduced derivatives served as inhibitor. A simple regression model was
      used to specify the structural requirements for a pteridine to be an inhibitor.
      The most characteristic features of an inhibitor are aromaticity and no
      substitution at position 7 of the pteridine ring.

PMID- 10082967
TI  - A group of alpha-1,4-glucan lyases and their genes from the red alga
      Gracilariopsis lemaneiformis: purification, cloning, and heterologous expression.
AB  - We present here the first report of a group of alpha-1,4-glucan lyases (EC
      4.2.2.13) and their genes. The lyases produce 1, 5-anhydro-D-fructose from starch
      and related oligomers and polymers. The enzymes were isolated from the red alga
      Gracilariopsis lemaneiformis from the Pacific coasts of China and USA, and the
      Atlantic Coast of Venezuela. Three lyase isozymes (GLq1, GLq2 and GLq3) from the
      Chinese subspecies, two lyase isozymes (GLs1 and GLs2) from the USA subspecies
      and one lyase (GLa1) from the Venezuelan subspecies were identified and
      investigated. GLq1, GLq3, GLs1 and GLa1 were purified and partially sequenced.
      Based on the amino acid sequences obtained, three lyase genes or their cDNAs
      (GLq1, GLq2 and GLs1) were cloned and completely sequenced and two other genes
      (GLq3 and GLs2) were partially sequenced. The coding sequences of the lyase genes
      GLq1, GLq2 and GLs1 are 3267, 3276 and 3279 bp, encoding lyases of 1088, 1091 and
      1092 amino acids, respectively. The deduced molecular masses of the mature lyases
      from the coding sequences are 117030, 117667 and 117790 Da, respectively, close
      to those determined by mass spectrometry using purified lyases. The amino acid
      sequence identity is more than 70% among the six algal lyase isozymes. The algal
      GLq1 gene was expressed in Pichia pastoris and Aspergillus niger, and the
      expression product was identical to the wild-type enzyme.

PMID- 10082968
TI  - Cloning and sequencing of cDNAs specifying a novel class of phosphoribosyl
      diphosphate synthase in Arabidopsis thaliana.
AB  - cDNAs specifying four active phosphoribosyl diphosphate synthase isozymes were
      isolated from an Arabidopsis thaliana cDNA library. In contrast to other
      phosphoribosyl diphosphate synthases the activity of two of the A. thaliana
      isozymes are independent of Pi. Amino acid sequence comparison and phylogenetic
      analysis indicate that these two isozymes belong to a novel class of
      phosphoribosyl diphosphate synthases.

PMID- 10082969
TI  - Phenotypic transformation of normal rat kidney fibroblasts by endothelin-1.
      Different mode of action from lysophosphatidic acid, bradykinin, and
      prostaglandin f2alpha.
AB  - In the present study, we compared the effects of endothelin (ET)-1 on cell
      proliferation and second messenger induction in normal rat kidney (NRK)
      fibroblasts, with those of other activators of G-protein-coupled receptors such
      as prostaglandin (PG)-F2alpha, bradykinin (BK), and lysophosphatidic acid (LPA).
      LPA is mitogenic by itself, while the other factors require the presence of EGF.
      In density-arrested NRK cells, ET-1 and LPA induce phenotypic transformation
      rapidly, with similar kinetics as retinoic acid (RA) and transforming growth
      factor (TGF)-beta, while BK and PGF2alpha only do so with delayed kinetics. ET-1
      and PGF2alpha are strong inducers of anchorage-independent growth, with a similar
      level of induction as TGFbeta, in contrast to LPA and BK. When investigating the
      second messenger generation, we found that ET-1 is the strongest activator of
      arachidonic acid release and phosphatidylinositol diphosphate hydrolysis. Only in
      the case of ET-1 the cell depolarization is not reversible upon removal of the
      factor. Similarly, only the ET-1-induced transient enhancement of intracellular
      calcium concentration is paralleled by both homologous and heterologous
      desensitization. In conclusion, these data show that ET-1 is a potent inducer of
      second messengers and phenotypic transformation in NRK cells, with
      characteristics that clearly differ from those of other activators of G-protein
      coupled receptors, most likely as a result of prolonged receptor activation.

PMID- 10082970
TI  - Differential usage of two 5' splice sites in a complex exon generates additional
      protein sequence complexity in chicken CLIP-170 isoforms.
AB  - Reverse transcription-polymerase chain reaction amplification and cloning of cDNA
      encoding the chicken CLIP-170(11) isoform of the Cytoplasmic Linker Protein 170
      gene revealed an unusual source of protein sequence variation. In addition to
      differential combinatorial splicing of two cassette exons to yield four CLIP-170
      protein isoforms, we found differential usage of alternative 5'-splice junctions
      in a single exon. Splicing at the downstream site yields message containing 18 bp
      of nucleotide sequence that is missing from message spliced at the more 5' site.
      This 18 bp sequence encodes a segment of 6 amino acids that fills a gap in the
      alignment of chicken and human CLIP-170 homologue sequences. Differential usage
      of the 5'-splice junctions in this complex exon appears to be tissue- rather than
      isoform-specific.

PMID- 10082971
TI  - Evidence for and consequences of chronic heme deficiency in Belgrade rat
      reticulocytes.
AB  - The Belgrade rat has a microcytic, hypochromic anemia inherited as an autosomal
      recessive trait (gene symbol b). Transferrin-dependent iron uptake is defective
      because of a mutation in Nramp2 (now DMT1, also called DCT1), the protein
      responsible for endosomal iron efflux. Hence, Belgrade reticulocytes are iron
      deficient. We show that a chromatographic method is able to measure the amount of
      'free' heme in reticulocytes. Most of the 'free' heme is the result of
      biosynthesis. Succinylacetone, an inhibitor of heme synthesis, decreases the
      level of 'free' heme and cycloheximide, an inhibitor of globin synthesis,
      increases the 'free' heme level. In a pulse-chase experiment with 59Fe
      transferrin, the 'free' heme pool behaves as an intermediate, with a half-life of
      just over 2 h. Belgrade reticulocytes contain about 40% as much 'free' heme as do
      heterozygous or homozygous reticulocytes. This deficiency of 'free' heme slows
      initiation of translation in Belgrade reticulocytes by increasing the level of an
      inhibitor of initiation. Thus the Belgrade rat makes a whole animal model
      available with chronic heme deficiency.

PMID- 10082972
TI  - Effect of inhibition of cholesterol synthetic pathway on the activation of Ras
      and MAP kinase in mesangial cells.
AB  - Intermediary metabolites of cholesterol synthetic pathway are involved in cell
      proliferation. Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, blocks mevalonate synthesis, and has been shown to inhibit mesangial
      cell proliferation associated with diverse glomerular diseases. Since inhibition
      of farnesylation and plasma membrane anchorage of the Ras proteins is one
      suggested mechanism by which lovastatin prevents cellular proliferation, we
      investigated the effect of lovastatin and key mevalonate metabolites on the
      activation of mitogen-activated protein kinase (MAP kinase) and Ras in murine
      glomerular mesangial cells. The preincubation of mesangial cells with lovastatin
      inhibited the activation of MAP kinase stimulated by either FBS, PDGF, or EGF.
      Mevalonic acid and farnesyl-pyrophosphate, but not cholesterol or LDL,
      significantly prevented lovastatin-induced inhibition of agonist-stimulated MAP
      kinase. Lovastatin inhibited agonist-induced activation of Ras, and mevalonic
      acid and farnesylpyrophosphate antagonized this effect. Parallel to the MAP
      kinase and Ras data, lovastatin suppressed cell growth stimulated by serum, and
      mevalonic acid and farnesylpyrophosphate prevented lovastatin-mediated inhibition
      of cellular growth. These results suggest that lovastatin, by inhibiting the
      synthesis of farnesol, a key isoprenoid metabolite of mevalonate, modulates Ras
      mediated cell signaling events associated with mesangial cell proliferation.

PMID- 10082973
TI  - The expression of casein kinase 2alpha' and phosphatase 2A activity.
AB  - Protein phosphatase 2A (PP2A) activity may be differentially regulated by the
      expression of proteins containing a related amino acid sequence motif such as the
      casein kinase 2alpha (CK2alpha) subunit or SV40 small t antigen (SVt). Expression
      of CK2alpha increases PP2A activity whereas SVt decreases its activity. In this
      work we have tested for the effect of the expression of a third protein
      containing a similar motif that could be involved in PP2A regulation, the
      catalytic casein kinase 2alpha' subunit. Our results show that despite the
      structural similarity of this protein with the other CK2 catalytic (alpha)
      subunit, the function of the two subunits with respect to the modulation of PP2A
      activity is quite different: CK2alpha increases whereas CK2alpha' slightly
      decreases PP2A activity.

PMID- 10082974
TI  - Wild-type NM23-H1, but not its S120 mutants, suppresses desensitization of
      muscarinic potassium current.
AB  - NM23 (NDP kinase) modulates the gating of muscarinic K+ channels by agonists
      through a mechanism distinct from GTP regeneration. To better define the function
      of NM23 in this pathway and to identify sites in NM23 that are important for its
      role in muscarinic K+ channel function, we utilized MDA-MB-435 human breast
      carcinoma cells that express low levels of NM23-H1. M2 muscarinic receptors and
      GIRK1/GIRK4 channel subunits were co-expressed in cells stably transfected with
      vector only (control), wild-type NM23-H1, or several NM23-H1 mutants. Lysates
      from all cell lines tested exhibit comparable nucleoside diphosphate (NDP) kinase
      activity. Whole cell patch clamp recordings revealed a substantial reduction of
      the acute desensitization of muscarinic K+ currents in cells overexpressing NM23
      H1. The mutants NM23-H1P96S and NM23-H1S44A resembled wild-type NM23-H1 in their
      ability to reduce desensitization. In contrast, mutants NM23-H1S120G and NM23
      H1S120A completely abolished the effect of NM23-H1 on desensitization of
      muscarinic K+ currents. Furthermore, NM23-H1S120G potentiated acute
      desensitization, indicating that this mutant retains the ability to interact with
      the muscarinic pathway, but has properties antithetical to those of the wild-type
      protein. We conclude that NM23 acts as a suppressor of the processes leading to
      the desensitization of muscarinic K+ currents, and that Ser-120 is essential for
      its actions.

PMID- 10082975
TI  - Measurements of [Ca2+] using fura-2 in glioma C6 cells expressing calretinin with
      GFP as a marker of transfection: no Ca2+-buffering provided by calretinin.
AB  - Glioma C6 cells were transfected with a plasmid containing the calretinin (CR)
      and green fluorescent protein (GFP) coding regions to analyze the effect of CR's
      presence on [Ca2+]i. Positive transfectants were identified by the detection of
      GFP and [Ca2+]i was measured using fura-2 as a probe. We found that neither the
      basic [Ca2+]i nor activated [Ca2+]i achieved by exposure to ionomycin, ADP or
      thapsigargin were affected by CR's presence in transfected cells, despite the
      ability of CR to bind Ca2+ as part of fusion protein. The level of expressed CR
      was estimated as at least 1 microM. The presented results suggest that CR's
      function is unlikely to be an intracellular Ca2+-buffer and support the
      hypothesis that CR might be involved in a specific Ca2+-dependent process. The
      results of this work also show that the S65T mutant of GFP is compatible with
      fura-2 measurements of intracellular [Ca2+]. We have demonstrated that the
      presence of GFP, as a transfection marker of glioma C6 cells, does not disturb
      fura-2 fluorescence, the basal or activated [Ca2+]i in these cells.

PMID- 10082976
TI  - Transforming growth factor-beta-induced upregulation of transforming growth
      factor-beta receptor expression in pancreatic regeneration.
AB  - The transforming growth factor-beta (TGFbeta) signaling pathway is one important
      player in the regulation of extracellular matrix turnover and cell proliferation
      in epithelial regeneration. We used cerulein-induced pancreatitis in rats as a
      model to investigate the regulation of TGFbeta receptor type I and type II
      expression on protein and messenger RNA level during regeneration. In the
      regenerating pancreas, mRNA levels of TGFbeta receptor I and II were
      significantly increased with a maximum after 2 days. On protein level, expression
      of TGFbeta receptor II was significantly increased after three to 3-5 days. This
      elevated expression could be inhibited by neutralizing the endogenous biological
      activity of TGFbeta1 with a specific antibody. In cultured pancreatic epithelial
      cells, TGFbeta1 reduced cell proliferation as measured by [3H]thymidine
      incorporation. Furthermore the transcript levels of TGFbeta1 as well as mRNA and
      protein concentrations of type I and type II receptor increased during TGFbeta
      stimulation in vitro. These results indicate that epithelial pancreatic cells
      contribute to the enhanced TGFbeta1 synthesis during pancreatic regeneration by
      an autocrine mechanism. TGFbeta1, furthermore, upregulates the expression of its
      own receptors during the regenerative process, thereby contributing to the
      increase of the TGFbeta-induced cellular responses.

PMID- 10082977
TI  - Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+
      oscillations in pituitary GH3 cells.
AB  - The present study investigates the potential role of the Ca2+-calmodulin
      dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in
      spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell
      videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE,
      induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations
      in these pituitary cells, and at the same time produced an increase of the
      intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP
      (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the
      amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823
      (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced
      an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i
      oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor
      counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor.
      Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage
      sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic
      cGMP levels. Collectively, the results of the present study suggest that
      spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of
      type I PDE-cGMP-PKG pathway.

PMID- 10082978
TI  - Antibody identification, chromosome map assignment, and sequence analysis of a
      Rab escort protein homolog in Drosophila1.
AB  - Using a polyclonal antiserum a cDNA encoding a Rab escort protein (REP) homolog
      in Drosophila has been identified and sequenced. The gene encodes a 511 residue
      protein with a predicted molecular mass of 56855 Da. Antibody labeling
      demonstrates that Drosophila REP protein is present in the early embryo and that
      it is being apportioned uniformly throughout the embryo in a process likely to be
      linked to the syncytial nuclear divisions. In situ hybridization to polytene
      chromosomes reveals that the Drosophila REP gene is located in the 56E region on
      the second chromosome. Drosophila REP is the first invertebrate REP homolog to be
      identified and characterized.

PMID- 10082979
TI  - Sequence and expression of a cDNA encoding the red sea bream androgen receptor.
AB  - The cDNA of the androgen receptor (AR) has been isolated from the ovary of red
      sea bream, Pagrus major, and sequenced. The amino acid sequence of red sea bream
      AR (rsAR) shows about 45% identity with that of Xenopus, rat, mouse, and human
      AR. It is shown that rsAR has the ability to trans-activate the responsive gene
      depending on the presence of androgen.

PMID- 10082980
TI  - Phylogenetic characterization of novel transport protein families revealed by
      genome analyses.
AB  - As a result of recent genome sequencing projects as well as detailed biochemical,
      molecular genetic and physiological experimentation on representative transport
      proteins, we have come to realize that all organisms possess an extensive but
      limited array of transport protein types that allow the uptake of nutrients and
      excretion of toxic substances. These proteins fall into phylogenetic families
      that presumably reflect their evolutionary histories. Some of these families are
      restricted to a single phylogenetic group of organisms and may have arisen
      recently in evolutionary time while others are found ubiquitously and may be
      ancient. In this study we conduct systematic phylogenetic analyses of 26 families
      of transport systems that either had not been characterized previously or were in
      need of updating. Among the families analyzed are some that are bacterial
      specific, others that are eukaryotic-specific, and others that are ubiquitous.
      They can function by either a channel-type or a carrier-type mechanism, and in
      the latter case, they are frequently energized by coupling solute transport to
      the flux of an ion down its electrochemical gradient. We tabulate the currently
      sequenced members of the 26 families analyzed, describe the properties of these
      families, and present partial multiple alignments, signature sequences and
      phylogenetic trees for them all.

PMID- 10082981
TI  - Metabolic pathways in the regulation of invertebrate and vertebrate Na+/Ca2+
      exchange.

PMID- 10082982
TI  - Manganese sulfate-dependent glycosylation of endogenous glycoproteins in human
      skeletal muscle is catalyzed by a nonglucose 6-P-dependent glycogen synthase and
      not glycogenin.
AB  - Glycogenin, a Mn2+-dependent, self-glucosylating protein, is considered to
      catalyze the initial glucosyl transfer steps in glycogen biogenesis. To study the
      physiologic significance of this enzyme, measurements of glycogenin mediated
      glucose transfer to endogenous trichloroacetic acid precipitable material
      (protein-bound glycogen, i.e., glycoproteins) in human skeletal muscle were
      attempted. Although glycogenin protein was detected in muscle extracts, activity
      was not, even after exercise that resulted in marked glycogen depletion. Instead,
      a MnSO4-dependent glucose transfer to glycoproteins, inhibited by glycogen and
      UDP-pyridoxal (which do not affect glycogenin), and unaffected by CDP (a potent
      inhibitor of glycogenin), was consistently detected. MnSO4-dependent activity
      increased in concert with glycogen synthase fractional activity after prolonged
      exercise, and the MnSO4-dependent enzyme stimulated glucosylation of
      glycoproteins with molecular masses lower than those glucosylated by glucose 6-P
      dependent glycogen synthase. Addition of purified glucose 6-P-dependent glycogen
      synthase to the muscle extract did not affect MnSO4-dependent glucose transfer,
      whereas glycogen synthase antibody completely abolished MnSO4-dependent activity.
      It is concluded that: (1) MnSO4-dependent glucose transfer to glycoproteins is
      catalyzed by a nonglucose 6-P-dependent form of glycogen synthase; (2) MnSO4
      dependent glycogen synthase has a greater affinity for low molecular mass
      glycoproteins and may thus play a more important role than glucose 6-P-dependent
      glycogen synthase in the initial stages of glycogen biogenesis; and (3)
      glycogenin is generally inactive in human muscle in vivo.

PMID- 10082983
TI  - ESR study on the structure-antioxidant activity relationship of tea catechins and
      their epimers.
AB  - The purpose of this study is to examine the relationship between the free radical
      scavenging activities and the chemical structures of tea catechins ((-)
      epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and (-)-epicatechin
      (EC)) and their corresponding epimers ((-)-gallocatechin gallate (GCG), (-)
      gallocatechin (GC) and (+)-catechin ((+)-C)). With electron spin resonance (ESR)
      we investigated their scavenging effects on superoxide anions (O-.2) generated in
      the irradiated riboflavin system, singlet oxygen(1O2) generated in the
      photoradiation-hemoporphyrin system, the free radicals generated from 2,2'
      azobis(2-amidinopropane)hydrochloride (AAPH) and 1, 1-diphenyl-2-picrylhydrazyl
      (DPPH) radical. The results showed that the scavenging effects of galloylated
      catechins (EGCG and GCG) on the four free radicals were stronger than those of
      nongalloylated catechins (EGC, GC, EC, (+)-C), and the scavenging effects of EGC
      and GC were stronger than those of EC and (+)-C. Thus, it is suggested that the
      presence of the gallate group at the 3 position plays the most important role in
      their free radical-scavenging abilities and an additional insertion of the
      hydroxyl group at the 5' position in the B ring also contributes to their
      scavenging activities. Moreover, the corresponding phenoxyl radicals formed after
      the reaction with O-.2 were trapped by DMPO and the ESR spectra of DMPO/phenoxyl
      radical adducts were observed (aN=15.6 G and aHbeta=21.5 G). No significant
      differences were found between the scavenging effects of the catechins and their
      epimers when their concentrations were high. However, significant differences
      were observed at relatively low concentrations, and the lower their
      concentrations, the higher the differences. The scavenging abilities of GCG, GC
      and (+)-C were stronger than those of their corresponding epimers (EGCG, EGC and
      EC). The differences between their sterical structures played a more important
      role in their abilities to scavenge large free radicals, such as the free
      radicals generated from AAPH and the DPPH radical, than to scavenge small free
      radicals, such as O-.2 and 1O2, especially in the case with EGCG and GCG with
      more bulky steric hindrance.

PMID- 10082984
TI  - Amphidinolide B, a powerful activator of actomyosin ATPase enhances skeletal
      muscle contraction.
AB  - Amphidinolide B caused a concentration-dependent increase in the contractile
      force of skeletal muscle skinned fibers. The concentration-contractile response
      curve for external Ca2+ was shifted to the left in a parallel manner, suggesting
      an increase in Ca2+ sensitivity. Amphidinolide B stimulated the
      superprecipitation of natural actomyosin. The maximum response of natural
      actomyosin to Ca2+ in superprecipitation was enhanced by it. Amphidinolide B
      increased the ATPase activity of myofibrils and natural actomyosin. The ATPase
      activity of actomyosin reconstituted from actin and myosin was enhanced in a
      concentration-dependent manner in the presence or absence of troponin-tropomyosin
      complex. Ca2+-, K+-EDTA- or Mg2+-ATPase of myosin was not affected by
      amphidinolide B. These results suggest that amphidinolide B enhances an
      interaction of actin and myosin directly and increases Ca2+ sensitivity of the
      contractile apparatus mediated through troponin-tropomyosin system, resulting in
      an increase in the ATPase activity of actomyosin and thus enhances the
      contractile response of myofilament.

PMID- 10082985
TI  - Accurate measurement of avidin and streptavidin in crude biofluids with a new,
      optimized biotin-fluorescein conjugate.
AB  - A new biotin-fluorescein conjugate with an ethylene diamine spacer was found to
      be the first fluorescent biotin derivative which truly mimicked d-biotin in terms
      of high affinity, fast association, and non-cooperative binding to avidin and
      streptavidin tetramers. These exceptional properties were attributed to the small
      size/length of the new ligand since all larger/longer biotin derivatives are
      known for their mutual steric hindrance and anti-cooperative binding in 4:1
      complexes with avidin and streptavidin tetramers. Specific binding of the new
      biotin-fluorescein conjugate towards avidin and streptavidin was accompanied by
      84-88% quenching of ligand fluorescence. In the accompanying study this effect
      was used for rapid estimation of avidin and streptavidin in a new 'single tube
      assay'. In the present study the strong quenching effect was utilized to
      accurately monitor stoichiometric titration of biotin-binding sites in samples
      with >/=200 pM avidin or streptavidin. The concentration was calculated from the
      consumption of fluorescent ligand up to the distinct breakpoint in the
      fluorescence titration profile which was marked by the abrupt appearance of
      strongly fluorescent ligands which were in excess. Due to this protocol the assay
      was not perturbed by background fluorescence or coloration in the unknown
      samples. The new fluorescence titration assay is particularly suited for quick
      checks on short notice because getting started only means to thaw an aliquot of a
      standardized stock solution of fluorescent ligand. No calibration is required for
      the individual assay and the ligand stock solution needs to be restandardized
      once per week (or once per year) when stored at -25 degrees C (or at -70 degrees
      C, respectively).

PMID- 10082986
TI  - Rapid estimation of avidin and streptavidin by fluorescence quenching or
      fluorescence polarization.
AB  - A new biotin-carboxyfluorescein conjugate has been presented in the accompanying
      study (G. Kada et al., Biochim. Biophys. Acta 000 (1999) 000-000) which contains
      ethylene diamine as a 4-atom spacer. This so-called biotin-4-fluorescein showed
      exceptionally fast and tight binding to avidin and streptavidin, and binding was
      accompanied by strong quenching. In the present study the specific quenching of
      'biotin-4-fluorescein' was utilized to measure (strept)avidin concentrations (0.2
      2 nM) by the extent of fluorescence quenching at 8 nM ligand concentration.
      Adsorption of (strept)avidin to the assay tubes was suppressed by inclusion of
      bovine serum albumin (0.1 mg/ml). Virtually the same specific response to avidin
      and streptavidin was also observed with commercial 'fluorescein-biotin', except
      that >10 h incubation times were required. The slow association of 'fluorescein
      biotin' was attributed to the anti-cooperative binding which is due to the much
      longer spacer as compared to 'biotin-4-fluorescein'. The third ligand tested in
      this study was 'biotin-4-FITC' which was analogous to 'biotin-4-fluorescein'
      except that carboxyfluorescein was replaced by the fluorescein isothiocyanate
      residue. Surprisingly, this probe was much less quenched by avidin but this was
      compensated by an exceptionally high fluorescence polarization in the avidin
      bound state. In conclusion, the new ligand 'biotin-4-fluorescein' appeared to be
      the most general and convenient probe: quenching was most pronounced and linearly
      dependent on (strept)avidin concentrations, the dose response for streptavidin
      was almost the same as for avidin, and the association kinetics were fast enough
      to reach equilibrium within 30 min incubation time.

PMID- 10082987
TI  - O-glycosylation potential of lepidopteran insect cell lines.
AB  - The enzyme activities involved in O-glycosylation have been studied in three
      insect cell lines, Spodoptera frugiperda (Sf-9), Mamestra brassicae (Mb) and
      Trichoplusia ni (Tn) cultured in two different serum-free media. The structural
      features of O-glycoproteins in these insect cells were investigated using a panel
      of lectins and the glycosyltransferase activities involved in O-glycan
      biosynthesis of insect cells were measured (i.e., UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase, UDP-Gal:core-1 beta1, 3-galactosyltransferase,
      CMP-NeuAc:Galbeta1-3GalNAc alpha2, 3-sialyltransferase, and UDP-Gal:Galbeta1
      3GalNAc alpha1, 4-galactosyltransferase activities). First, we show that O
      glycosylation potential depends on cell type. All three lepidopteran cell lines
      express GalNAcalpha-O-Ser/Thr antigen, which is recognized by soy bean agglutinin
      and reflects high UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
      activity. Capillary electrophoresis and mass spectrometry studies revealed the
      presence of at least two different UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferases in these insect cells. Only some O-linked GalNAc
      residues are further processed by the addition of beta1,3-linked Gal residues to
      form T-antigen, as shown by the binding of peanut agglutinin. This reflects
      relative low levels of UDP-Gal:core-1 beta1,3-galactosyltransferase in insect
      cells, as compared to those observed in mammalian control cells. In addition, we
      detected strong binding of Bandeiraea simplicifolia lectin-I isolectin B4 to
      Mamestra brassicae endogenous glycoproteins, which suggests a high activity of a
      UDP-Gal:Galbeta1-3GalNAc alpha1, 4-galactosyltransferase. This explains the
      absence of PNA binding to Mamestra brassicae glycoproteins. Furthermore, our
      results substantiated that there is no sialyltransferase activity and, therefore,
      no terminal sialic acid production by these cell lines. Finally, we found that
      the culture medium influences the O-glycosylation potential of each cell line.

PMID- 10082988
TI  - Lack of effect of carbohydrate depletion on some properties of human mast cell
      chymase.
AB  - Human chymase from vascular tissues was purified to homogeneity by heparin
      affinity and gel filtration chromatography. Treatment of human chymase with
      endoglycosidase F resulted in cleavage of the carbohydrate moiety yielding a
      deglycosylation product that did not lose its catalytic activity. This enzymatic
      deglycosylation product was enough to explore possibilities that N-glycan might
      modify some properties of human chymase. Substrate specificity, optimum pH and
      the elution profile from the heparin affinity gel were not affected by the
      deglycosylation. Only a slight but significant difference was observed in the Km
      value for conversion of angiotensin I to angiotensin II. Other kinetic constants
      such as kcat were not influenced. The kinetics of conversion of big endothelin-1
      to endothelin-1(1-31) were not significantly affected. The deglycosylated human
      chymase was more susceptible to deactivation under alkaline pH and thermal
      stress. Even at physiological temperature and pH, the activity of glycosylated
      human chymase was more stable. From these results, it appears that the N-glycan
      of human chymase contributes to the stability of this enzyme but not to its
      functional properties.

PMID- 10082989
TI  - A novel high molecular weight fibrinogenase from the venom of Bitis arietans.
AB  - A fibrinogenase (Ba100) with an apparent molecular mass of 100 kDa under non
      reducing conditions and a pI of 5.4 was purified from the venom of the African
      puff adder (Bitis arietans) by fibrinogen affinity chromatography. Under reducing
      conditions the protease dissociates into subunits of 21 kDa and 16 kDa. N
      Terminal amino acid sequencing showed these two chains to have 66.7% homology and
      homology to C-type lectins. The fibrinogenase activity of Ba100 cleaves the
      Aalpha and Bbeta chain of fibrinogen rendering the molecule unable to polymerise
      into fibrin clots. Ba100 inhibited platelet aggregation in platelet rich plasma,
      and clot formation in whole blood, in a concentration dependent manner.

PMID- 10082990
TI  - Identification, characterisation and cDNA cloning of two caseins from the common
      brushtail possum (Trichosurus vulpecula)1.
AB  - Two major caseins have been isolated from the milk of the common brushtailed
      possum (Trichosurus vulpecula). These have been identified as alpha- and beta
      casein on the basis of the similarity of their N-terminal sequences to those of
      the caseins of another marsupial (Macropus eugenii). Both proteins appear to
      exist in multiple forms. Possum alpha-casein is glycosylated mainly in the form
      of sialic acid residues and was shown by electrospray mass spectrometry to have
      multiply phosphorylated forms of three families with molecular masses 22700 and
      23200 Da that may represent genetic variants. Two-dimensional electrophoresis
      showed that beta-casein exists as a complex of five or six proteins of identical
      N-terminal sequence but differing pI. Electrospray mass spectrometry indicated
      that the beta-caseins also are multiply phosphorylated with masses between 32300
      and 32600 Da. A subfamily with mass values 1530 greater was also detected. The
      patterns were not affected by stage of lactation and quantitative analysis of two
      dimensional gels of whole milk shows that alpha- and beta-caseins are present at
      a constant ratio throughout lactation. cDNA clones for the possum alpha- and beta
      caseins have been isolated from an early lactation mammary cDNA library and
      sequenced.

PMID- 10082991
TI  - Interaction of 75-106 actin peptide with myosin subfragment-1 and its trypsin
      modified derivative.
AB  - To explore the role of a hydrophobic domain of actin in the interaction with a
      myosin chain we have synthesized a peptide corresponding to residues 75-106 of
      native actin monomer and studied by fluorescence and ELISA the interaction (13+/
      2.6x10(-6) M) with both S-1 and (27 kDa-50 kDa-20 kDa) S-1 trypsin derivative of
      myosin. The loop corresponding to 96-103 actin residues binds to the S-1 only in
      the absence of Mg-ATP and under similar conditions but not to the trypsin
      derivative S-1. Biotinylated C74-K95 and I85-K95 peptide fragments were purified
      after actin proteolysis with trypsin. The C74-K95 peptide interacted with both S
      1 and the S-1 trypsin derivative with an apparent Kd(app) of 6+/-1.2x10(-6) M in
      the presence or absence of nucleotides. Although peptide fragment I85-K95 binds
      to S-1 with a Kd(app) of 12+/-2.4x10(-6) M, this fragment did not bind to the
      trypsin S-1 derivative. We concluded that the actin 85-95 sequence should be a
      potential binding site to S-1 depending of the conformational state of the intact
      70 kDa segment of S-1.

PMID- 10082992
TI  - Quercetin inhibited DNA synthesis and induced apoptosis associated with increase
      in c-fos mRNA level and the upregulation of p21WAF1CIP1 mRNA and protein
      expression during liver regeneration after partial hepatectomy.
AB  - Quercetin, a widely distributed bioflavonoid, inhibited DNA synthesis in
      regenerating liver after partial hepatectomy. This inhibition was accompanied by
      apoptosis, evidenced by in situ end-labeling and gel electrophoresis of DNA
      fragmentation. Characteristic DNA fragmentation was detected as early as 2 h
      after injection. Northern blot analysis revealed that quercetin induced the
      increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21
      protein was also enhanced, while p53 mRNA and protein levels were not affected by
      quercetin. These results suggest that quercetin-induced apoptosis is associated
      with the increase in c-fos mRNA level and the upregulation of p21 mRNA and
      protein expression, probably in a p53-independent pathway.

PMID- 10082993
TI  - Active site characterization of the exo-N-acetyl-beta-D- glucosaminidase from
      thermotolerant Bacillus sp. NCIM 5120: involvement of tryptophan, histidine and
      carboxylate residues in catalytic activity.
AB  - The exo-N-acetyl-beta-d-glucosaminidase (EC 3.2.1.30) from thermotolerant
      Bacillus sp. NCIM 5120 is a homotetramer with a molecular mass of 240000 kDa.
      Chemical modification studies on the purified exo-N-acetyl-beta-d-glucosaminidase
      revealed the involvement of a single tryptophan, histidine and carboxylate, per
      monomer, in the catalytic activity of the enzyme. Spectral analysis and
      maintenance of total enzyme activities indicated that N-acetylglucosamine
      (competitive inhibitor) and p-nitrophenyl-N-acetyl-beta-d-glucosaminide
      (substrate) prevented the modification of a single essential tryptophan,
      histidine and carboxylate residue. Kinetic parameters of partially inactivated
      enzyme (by NBS/HNBB) showed the involvement of tryptophan in substrate binding
      while that of histidine (by photooxidation/DEPC) and carboxylate (by EDAC/WRK) in
      catalysis. The Bacillus sp. NCIM 5120 exo-N-acetyl-beta-d-glucosaminidase
      deviates from the reported N-acetyl-beta-d-glucosaminidases and beta
      hexosaminidases that utilize anchimeric assistance in their hydrolytic mechanism.

PMID- 10082994
TI  - The XVII World Congress of the Transplantation Society: new visions and new
      solutions.

PMID- 10082995
TI  - A half-century retrospective of transplantation as viewed by the protagonists.

PMID- 10082996
TI  - A 50-year retrospective: cell-mediated immunity and the major histocompatibility
      complex.

PMID- 10082997
TI  - Reminiscences.

PMID- 10082998
TI  - A half-century retrospective of transplantation as viewed by the protagonists: my
      own reminiscences.

PMID- 10082999
TI  - The HLA adventure.

PMID- 10083000
TI  - The first lung transplant in man (1963) and the first heart transplant in man
      (1964).

PMID- 10083001
TI  - Humoral transplantation antibodies.

PMID- 10083002
TI  - Reminiscences for the "50-year retrospective" of transplantation.

PMID- 10083003
TI  - Reminiscences in the "half-century retrospective" symposium.

PMID- 10083004
TI  - The development of immunosuppressive therapy: from leukemia to transplantation.

PMID- 10083005
TI  - The ascension of clinical organ transplantation.

PMID- 10083006
TI  - Forty years of thoracic transplantation at Stanford.

PMID- 10083007
TI  - History of some currently utilized procedures in transplantation.

PMID- 10083008
TI  - Reminiscences of Peter Medawar.

PMID- 10083009
TI  - Introduction of Fritz Bach, Medawar Prize Laureate.

PMID- 10083010
TI  - Medawar Prize Lecture. The intimate relationship of the MHC with T lymphocytes.

PMID- 10083011
TI  - Introduction of Felix Rapaport for 1998 Medawar Prize.

PMID- 10083012
TI  - Medawar Prize Lecture, 15 July 1998. The contribution of human subjects to
      experimental transplantation: the HLA story.

PMID- 10083013
TI  - Antilymphocyte serum, donor bone marrow and tolerance to allografts: the journey
      is the reward.

PMID- 10083014
TI  - Cardiac transplantation in patients over 60 years of age.

PMID- 10083015
TI  - Optimal timing for surveillance endomyocardial biopsies in heart transplant
      patients receiving antithymocyte globulin induction.

PMID- 10083016
TI  - Effects of continuous, long-term therapy with prostaglandin E1 preoperatively on
      outcome after heart transplantation.

PMID- 10083017
TI  - Tacrolimus: a cause of hypertrophic cardiomyopathy in pediatric heart transplant
      recipients?

PMID- 10083018
TI  - The efficacy of the combination of tacrolimus and mycophenolate mofetil for
      prevention of acute myocardial rejection is dependent on routine monitoring of
      mycophenolic acid trough acid levels.

PMID- 10083019
TI  - Renal complications after heart transplantation.

PMID- 10083020
TI  - Platelet-derived growth factor rather than basic fibroblast growth factor and
      vascular endothelial cell growth factor is involved in adventitial narrowing
      causing vascular stenosis in end-stage cardiac allograft vasculopathy.

PMID- 10083021
TI  - In vivo cytokine production by allospecific CD8+ transgenic T cells after heart
      transplantation.

PMID- 10083022
TI  - CD4 T cells acutely reject cardiac allografts via direct donor recognition.

PMID- 10083023
TI  - Evidence for a role of IL-17 in alloimmunity: a novel IL-17 antagonist promotes
      heart graft survival.

PMID- 10083024
TI  - Intrathymic inoculation of donor B cells prolongs cardiac allograft survival by
      non-deletional mechanisms.

PMID- 10083025
TI  - Prolonged anti-CD40 ligand therapy improves primate cardiac allograft survival.

PMID- 10083026
TI  - Myocardial nitric oxide synthase gene-expression and endothelial function in
      chronic rejection after cardiac transplantation.

PMID- 10083027
TI  - C677T gene mutation in methylenetetrahydrofolate reductase as a risk factor for
      cardiac allograft vasculopathy.

PMID- 10083028
TI  - Persistent allopeptide reactivity and epitope spreading in chronic rejection.

PMID- 10083030
TI  - Effect of low molecular weight heparin on graft vascular disease in the rat
      cardiac allograft model.

PMID- 10083029
TI  - Prevention of cardiac allograft arteriosclerosis by protein-tyrosine kinase
      inhibitor selective for platelet-derived growth factor receptor.

PMID- 10083031
TI  - TCV-116 reduces chronic rejection in a rat heterotopic cardiac transplant model.

PMID- 10083032
TI  - The effects of heart/kidney versus double heart transplantation on tolerance
      induction and prevention of cardiac allograft vasculopathy.

PMID- 10083033
TI  - Changes in cell cycling and apoptosis contribute to reduced effector cell
      generation among long-term heart transplant survivors.

PMID- 10083034
TI  - Growth factors and receptors in allograft arteriosclerosis.

PMID- 10083035
TI  - Recipient pretreatment with mammalian IL-10 prolongs mouse cardiac allograft
      survival by inhibition of anti-donor T cell responses.

PMID- 10083036
TI  - Cold cardioplegic preservation aggravates alloantibody mediated cardiac
      dysfunction due to an increase in vascular resistance.

PMID- 10083037
TI  - Evaluation of a new protection technique for heart preservation of non-heart
      beating donors.

PMID- 10083038
TI  - Bridging to cardiac transplantation: a clinical laboratory for the development of
      mechanical alternatives to transplantation.

PMID- 10083039
TI  - Immune nonresponsiveness to cardiac allografts by intrathymic inoculation of
      donor class I allopeptides is associated with high levels of transcripts for Th2
      cytokines in the graft.

PMID- 10083040
TI  - Photopheresis after cardiac transplantation induces apoptosis.

PMID- 10083041
TI  - Photopheresis for recurrent acute rejection in cardiac transplantation.

PMID- 10083042
TI  - In vivo differentiation of alloreactive CD8+ T cells after murine cardiac
      allograft transplantation.

PMID- 10083043
TI  - Quantitative analysis of PDGFA, PDGFB, PDGF receptor beta and TGF-beta 1 mRNA in
      cardiac transplant biopsies.

PMID- 10083044
TI  - Tolerance in murine cardiac allografts by concurrent infusion of viable donor
      antigen-bearing cells.

PMID- 10083045
TI  - Hearts lacking donor-type APCs develop cardiac allograft vasculopathy.

PMID- 10083046
TI  - Inhibition of acute cardiac allograft rejection in immunoglobulin-deficient mice.

PMID- 10083047
TI  - Troponin T serum levels in donors related to troponin T levels in recipients
      immediately after heart transplantation.

PMID- 10083048
TI  - Passenger leukocytes from a heart allograft can induce lethal lymphoid aplasia.

PMID- 10083049
TI  - Antiphospholipid antibodies in left-ventricular assist system recipients after
      exposure to topical bovine thrombin.

PMID- 10083050
TI  - Inhibitory effect of 15-deoxyspergualin on coronary arteriosclerosis in the
      transplanted heart.

PMID- 10083051
TI  - Myocardial preservation in clinical cardiac transplantation.

PMID- 10083052
TI  - Light microscopic biopsy findings after heart transplantation and possible links
      to development of graft vessel disease.

PMID- 10083053
TI  - Deficiencies of IL-4 or TNF-alpha receptor-1 do not diminish graft
      arteriosclerosis in cardiac allografts.

PMID- 10083054
TI  - Orthotopic transplantation of pig hearts harvested from non-heart-beating donors.

PMID- 10083055
TI  - Value of sequential big endothelin plasma concentrations to predict rapid
      worsening of chronic heart failure.

PMID- 10083056
TI  - Contribution of passenger leukocytes to the induction and maintenance of heart
      allograft acceptance.

PMID- 10083057
TI  - Vascular rejection in cardiac transplantation.

PMID- 10083058
TI  - Detailed analysis of cell profiles in peripheral blood, bronchoalveolar lavage
      fluid, and transbronchial biopsy specimens during acute rejection and CMV
      infection in lung and heart-lung allograft recipients.

PMID- 10083059
TI  - Review of the current state of thoracic transplantation: a national prospective
      cohort study. UK Cardiothoracic Transplant Audit Steering Group.

PMID- 10083060
TI  - Extracorporeal membrane oxygenation support for single-lung transplantation in
      patients with primary pulmonary hypertension.

PMID- 10083061
TI  - Importance of an aggressive multidisciplinary management approach to optimize
      lung donor procurement.

PMID- 10083062
TI  - Tacrolimus-based immunosuppressive protocols in lung transplantation.

PMID- 10083063
TI  - Two types of CMV-specific memory responses in lung transplant recipients.

PMID- 10083064
TI  - Role of infections, pathogenesis, and management in lung transplantation.

PMID- 10083065
TI  - Simultaneous estimation of pulmonary edema and tissue oxygenation by near
      infrared spectroscopy.

PMID- 10083066
TI  - Administration of exogenous interleukin-2 enhances obliterative airway disease in
      cyclosporine-treated rats following tracheal allografts.

PMID- 10083067
TI  - Alterations in inducible nitric oxide synthase (iNOS) and nitrotyrosine (NitroY)
      during re-epithelialization of heterotopic rat tracheal composite grafts.

PMID- 10083068
TI  - Reduction of lung allograft ischemia/reperfusion injury by tetrahydrobiopterin
      coenzyme of NOS.

PMID- 10083069
TI  - Temporal relationship between the development of anti-HLA antibodies and the
      development of bronchiolitis obliterans syndrome after lung transplantation.

PMID- 10083070
TI  - Inhibition of obliterative bronchiolitis by platelet-derived growth factor
      receptor protein-tyrosine kinase inhibitor.

PMID- 10083071
TI  - Inhibition of complement reduces obliterative bronchiolitis.

PMID- 10083072
TI  - The influence of ischemia on the severity of chronic rejection in a rat lung
      transplant model.

PMID- 10083073
TI  - Extracellular matrix composition of obliterated bronchioli in lung transplant
      recipients.

PMID- 10083074
TI  - Na+/K(+)-ATPase activity in rat lungs preserved with EP4 solution.

PMID- 10083075
TI  - Function of CD4+ cytolytic T lymphocytes in lung allografts.

PMID- 10083076
TI  - Breakthrough Pneumocystis carinii infections in lung and heart-lung transplant
      patients with chemoprophylaxis.

PMID- 10083077
TI  - Passive transfer of anti-donor antibodies in a rat lung transplant model.

PMID- 10083078
TI  - Living related and cadaveric kidney transplantation--what are the major
      differences?

PMID- 10083079
TI  - Asian transplant registry.

PMID- 10083080
TI  - Developments in transplantation in Taiwan.

PMID- 10083081
TI  - Latin American Transplant Registry VIIIth Report: 1998.

PMID- 10083082
TI  - Validity of open labeled versus blinded trials: a meta-analysis comparing Neoral
      and Sandimmune.

PMID- 10083083
TI  - Factors affecting development of function, level of function, and 36-month graft
      survival--multivariant analysis.

PMID- 10083084
TI  - Recurrent and de novo glomerular disease after renal transplantation: a report
      from renal allograft disease registry.

PMID- 10083085
TI  - Influence of an historically positive crossmatch on cadaveric renal
      transplantation.

PMID- 10083086
TI  - Anticardiolipin antibodies after kidney transplantation in patients without
      connective tissue disease.

PMID- 10083087
TI  - Antiphospholipid antibody syndrome and posttransplant renal thrombosis.

PMID- 10083088
TI  - Results of more than 1000 recent living-unrelated donor transplants in the United
      States.

PMID- 10083089
TI  - Risk of primary disease recurrence in pediatric renal transplantation.

PMID- 10083090
TI  - Transplantation of adult-sized kidneys into infants induces major blood flow
      changes.

PMID- 10083091
TI  - Lessons from cytomegalovirus disease in pediatric kidney transplantation.

PMID- 10083092
TI  - Developmental well-being in offspring of women receiving cyclosporine post-renal
      transplant.

PMID- 10083093
TI  - Immunologically high-risk recipient strategies.

PMID- 10083094
TI  - Corticosteroid withdrawal in renal transplantation.

PMID- 10083095
TI  - Comparison of two corticosteroid regimens in combination with CellCept and
      cyclosporine A for prevention of acute allograft rejection: 12 month results of a
      double-blind, randomized, multi-center study. M 55002 Study Group.

PMID- 10083096
TI  - Psychiatric symptoms during the week after renal transplantation.

PMID- 10083097
TI  - Contemporary immunosuppression in renal transplant recipients: one size does not
      fit all.

PMID- 10083098
TI  - Long-term follow-up of ABO-incompatible renal transplant recipients.

PMID- 10083099
TI  - Equivalent renal allograft function with laparoscopic versus open liver donor
      nephrectomies.

PMID- 10083100
TI  - Predictive value of histopathology and function on outcome of renal allografts
      after acute rejection.

PMID- 10083101
TI  - De novo and recurrent diseases: recurrent glomerulopathies.

PMID- 10083102
TI  - Zenapax (daclizumab) reduces the incidence of acute rejection episodes and
      improves patient survival following renal transplantation. No 14874 and No 14393
      Zenapax Study Groups.

PMID- 10083103
TI  - High risk kidney transplant rejection treatment: cost savings from thymoglobulin.

PMID- 10083104
TI  - Mycophenolate mofetil-induced colonic ulceration in renal transplant recipients.

PMID- 10083105
TI  - One-year, single-center cost analysis of mycophenolate mofetil versus
      azathioprine following cadaveric renal transplantation.

PMID- 10083106
TI  - Tacrolimus and mycophenolate mofetil in renal transplant recipients: one year
      results of a multicenter, randomized dose ranging trial. FK506/MMF Dose-Ranging
      Kidney Transplant Study Group.

PMID- 10083107
TI  - Rejection rate and incidence of acute tubular necrosis after pulsatile perfusion
      preservation.

PMID- 10083108
TI  - Odds probabilities of compliance and noncompliance in patients with a functioning
      renal transplant: a multicenter study.

PMID- 10083109
TI  - Detection of allo- and autoantibodies in kidney transplantation by flow
      cytometry.

PMID- 10083110
TI  - Antiphospholipid antibodies are a risk factor for early renal allograft failure:
      isolation of antiphospholipid antibodies from a thrombosed renal allograft.

PMID- 10083111
TI  - Is renal graft survival predetermined by the recipient's cytokine profile?

PMID- 10083112
TI  - Risk issues in renal transplantation: cardiac aspects.

PMID- 10083113
TI  - Kidneys from border-age donors in the cyclosporine era: long-term function and
      outcome.

PMID- 10083114
TI  - Low systemic exposure to tacrolimus correlates with acute rejection.

PMID- 10083115
TI  - P-glycoprotein expression in patients before and after kidney transplantation.

PMID- 10083116
TI  - Incidence and cost of steroid side effects after renal transplantation.

PMID- 10083117
TI  - Does cyclosporine influence the outcome in patients with acute tubular necrosis
      after renal transplantation.

PMID- 10083118
TI  - Impaired vascular responsiveness to nitric oxide in renal transplant recipients.

PMID- 10083119
TI  - Kidney graft-infiltrating cells synthesize significantly higher amounts of
      prostaglandin E2 pre and during acute rejection.

PMID- 10083120
TI  - Nucleic acid sequence-based amplification: a new technique for monitoring
      cytomegalovirus infection in transplant recipients.

PMID- 10083121
TI  - A novel monitoring of kidney allograft rejection with plasma EDA(+) fibronectin.

PMID- 10083122
TI  - Effect of race on kidney transplant survival in non-European recipients.

PMID- 10083123
TI  - Flow cytometry crossmatch and kidney graft outcome.

PMID- 10083124
TI  - Experimental study of the role of nitric oxide in acute renal allograft
      rejection.

PMID- 10083125
TI  - Predictive value of the CD45RO positive T-helper lymphocyte subset for acute
      cellular rejection during the early phase after kidney transplantation.

PMID- 10083126
TI  - Mycophenolate mofetil improves long-term graft survival following renal
      transplantation in patients experiencing delayed graft function. International
      Mycophenolate Mofetil Renal Study Groups.

PMID- 10083127
TI  - Nine-month follow-up of SangCya (Sang-35) in kidney transplant patients after
      conversion from Sandimmune.

PMID- 10083128
TI  - Pharmacokinetic and safety evaluation of SangCya vs Neoral or Sandimmune in
      stable renal transplant recipients.

PMID- 10083129
TI  - Cellcept enhances the rate of apoptosis in T cells after renal transplantation.

PMID- 10083130
TI  - Beneficial effects of conversion from cyclosporine to azathioprine on
      fibrinolysis in renal transplant recipients.

PMID- 10083131
TI  - Tacrolimus in renal transplantation: a comparison of induction vs noninduction
      therapy (triple therapy): three-month results.

PMID- 10083132
TI  - Postischemic reperfusion injury and allograft dysfunction: is allograft rejection
      the result of a fateful confusion by the immune system of danger and benefit?

PMID- 10083133
TI  - Viral hepatitis in renal transplantation.

PMID- 10083134
TI  - Complete reversal of acute rejection episodes after syngeneic retransplantation
      is associated with a TH1/TH2 shift.

PMID- 10083135
TI  - T-cell growth factors in allograft rejection and tolerance.

PMID- 10083136
TI  - Exchange-donor program in renal transplantation: a single-center experience.

PMID- 10083137
TI  - Cadaver kidney transplantation in Catalonia: successful organization.

PMID- 10083138
TI  - Risk factors in renal transplantation and implications for immunosuppressive
      therapy.

PMID- 10083139
TI  - An alternative approach to evaluating organ procurement organization performance.

PMID- 10083140
TI  - Exchange-donor program in kidney transplantation.

PMID- 10083141
TI  - A new allocation plan for renal transplantation.

PMID- 10083142
TI  - Early graft failure with thrombophilia and effects of anticoagulation.

PMID- 10083143
TI  - Impact of early vesico ureteral reflux on the transplanted kidney.

PMID- 10083144
TI  - Early changes in kidney function following living donor nephrectomy.

PMID- 10083145
TI  - Remnant kidney function in kidney donors.

PMID- 10083146
TI  - Using ANN in selection of the most important variables in prediction of chronic
      renal allograft rejection progression.

PMID- 10083147
TI  - Artificial liver.

PMID- 10083148
TI  - Report from studies of pediatric liver transplantation (SPLIT). SPLIT Research
      Group.

PMID- 10083149
TI  - Evaluation of patient selection criteria for liver transplantation: eight-year
      experience.

PMID- 10083150
TI  - Quick correction of hemostasis in two patients with fulminant liver failure
      undergoing liver transplantation by recombinant activated factor VII.

PMID- 10083151
TI  - Quadruple induction therapy including antithymocyte globulin or interleukin-2
      receptor antibody or FK 506-based induction therapy after liver transplantation.

PMID- 10083152
TI  - Living donor liver transplantation: an 8-year experience with 379 consecutive
      cases.

PMID- 10083153
TI  - Orthotopic liver transplantation for hepatic-associated metabolic disorders.

PMID- 10083154
TI  - Impairment of hepatic microcirculation as an early manifestation of acute
      rejection after clinical liver transplantation.

PMID- 10083155
TI  - Predictors of early discharge after orthotopic liver transplantation.

PMID- 10083156
TI  - Serum lipid changes in liver transplantation: effect of steroids withdrawn in a
      prospective randomized trial under cyclosporine A therapy.

PMID- 10083157
TI  - Pharmacokinetic comparison of two cyclosporine A formulations, SangCya (Sang-35)
      and Neoral, in stable adult liver transplant recipients.

PMID- 10083158
TI  - Mycophenolate mofetil rescue therapy in patients with chronic hepatic allograft
      rejection.

PMID- 10083159
TI  - Marginal donors in liver transplantation: the role of donor age.

PMID- 10083160
TI  - Is the use of marginal liver grafts justified?

PMID- 10083161
TI  - Effects of fatty infiltration of the graft on the outcome of living-related liver
      transplantation.

PMID- 10083162
TI  - Clinical and neurophysiological evidence of polyneuropathy in liver transplant
      candidates: preliminary report.

PMID- 10083163
TI  - Impact of early arterialization in the liver allograft.

PMID- 10083164
TI  - Noncompliance after pediatric liver transplantation.

PMID- 10083165
TI  - Mechanism of liver allograft rejection: indirect allorecognition.

PMID- 10083166
TI  - Sulfur-containing metabolites of N-acetylcysteine in patients undergoing
      orthotopic liver transplantation.

PMID- 10083167
TI  - Is a fatty liver dangerous for transplantation?

PMID- 10083168
TI  - Treatment of hepatocellular carcinoma: pathologic results after chemoembolization
      and liver transplantation.

PMID- 10083169
TI  - 18F-fluorodeoxyglucose positron emission tomography study of brain metabolism in
      cirrhosis: effect of liver transplantation.

PMID- 10083170
TI  - Experimental evaluation of dynamic MRI for quantification of liver perfusion.

PMID- 10083171
TI  - Fas/Apo-1 expression of human GVHD livers. Bone Marrow Transplantation Group.

PMID- 10083172
TI  - Involvement of Kupffer cells and sinusoidal endothelial cells in ischemic
      preconditioning to rat livers stored for transplantation.

PMID- 10083173
TI  - Hepatocyte transplantation improves liver function and prolongs survival in rats
      with decompensated liver cirrhosis.

PMID- 10083174
TI  - Recurrence of autoimmune hepatitis after liver transplantation.

PMID- 10083175
TI  - Role of indirect allorecognition pathway for prolongation of rat liver allograft
      survival.

PMID- 10083176
TI  - Primary dysfunction after liver transplantation: donor or recipient fault?

PMID- 10083177
TI  - Donor cell population in the liver allograft reflects the recipient immune
      status.

PMID- 10083178
TI  - Thymic and liver graft expression of CD95-L tolerizes allogeneic orthotopic liver
      grafts.

PMID- 10083179
TI  - Use of high-risk liver donors for urgent and elective liver transplantation.

PMID- 10083180
TI  - Excision and immediate revascularization for hepatic artery pseudoaneurysm
      following liver transplantation.

PMID- 10083181
TI  - Diminished portal and total hepatic blood flows after liver graft
      revascularization predicts severity of ischemic lesion.

PMID- 10083182
TI  - Effects of adenosine on dopamine-induced hepatic impairment in the dog model.

PMID- 10083183
TI  - Avoidance of postreperfusional endotoxemia and hepatic energy depression by
      intraoperative lipid infusion in porcine liver transplantation.

PMID- 10083184
TI  - Mechanisms of suppression of liver allograft rejection by LSF-1.

PMID- 10083185
TI  - Treatment with CTLA4-Ig inhibits rejection of liver allografts from FIt3-ligand
      treated donors.

PMID- 10083186
TI  - Evidence for the presence of hepatic stem cells in the murine fetal liver.

PMID- 10083187
TI  - Antigen load and liver allograft survival.

PMID- 10083188
TI  - Adult-to-adult living donor liver transplantation at Asian Medical Center, Seoul,
      Korea.

PMID- 10083189
TI  - Course and mechanism of tolerance induction after mouse liver transplantation.

PMID- 10083190
TI  - Endothelin antagonist improves viability of liver grafts from non-heart-beating
      donors.

PMID- 10083191
TI  - Indications for determination of alpha-glutathione-s-transferase after liver
      transplantation.

PMID- 10083192
TI  - Influence of Th1 and Th2 cytokine patterns on graft acceptance in pediatric liver
      transplantation.

PMID- 10083193
TI  - Long-term results in pediatric ABO-incompatible liver transplantation.

PMID- 10083194
TI  - Liver transplantation for hepatocellular carcinoma.

PMID- 10083195
TI  - Calcitriol in prevention and therapy of osteoporosis after liver transplantation.

PMID- 10083196
TI  - Apoptosis of alloreactive T cells in liver allografts during tolerance induction.

PMID- 10083197
TI  - Adenoviral-mediated gene delivery to liver isografts: improved model of ex vivo
      gene transfer.

PMID- 10083198
TI  - Quantitation of hepatitis C virus RNA in liver tissue of allografts: correlation
      with histologic features and liver function tests.

PMID- 10083199
TI  - Human herpesvirus 6 infection increases adhesion molecule expression in liver
      allografts.

PMID- 10083200
TI  - Treatment of hepatitis B-reinfection or de novo-infection after liver
      transplantation with famciclovir--how effective is it?

PMID- 10083201
TI  - Immunogenetic factors, HCV genotypes, and HCV recurrence after liver
      transplantation.

PMID- 10083202
TI  - Developing strategies for prevention and treatment of recurrent HBV in liver
      transplantation.

PMID- 10083203
TI  - Cytomegalovirus detected in the upper gastrointestinal tract parallel with CMV
      antigenemia in liver transplant patients.

PMID- 10083204
TI  - Natural history of Epstein-Barr viral load in peripheral blood of pediatric liver
      transplant recipients during treatment for posttransplant lymphoproliferative
      disorder.

PMID- 10083205
TI  - Hepatitis C reinfection after liver transplantation in relation to virus
      genotype.

PMID- 10083206
TI  - Hepatitis B virus variants associated with clinically severe recurrence after
      liver transplantation.

PMID- 10083207
TI  - Treatment of severe recurrent hepatitis C after liver transplantation with
      ribavirin plus interferon alpha.

PMID- 10083208
TI  - Hepatitis G virus infection in liver transplant recipients.

PMID- 10083209
TI  - Is liver transplantation superior to resection in early stage hepatocellular
      carcinoma?

PMID- 10083210
TI  - Interference of soluble mediators into liver matrix triggered dedifferentiation
      of human hepatocytes.

PMID- 10083211
TI  - Glycine rinse protects against liver injury during transplantation.

PMID- 10083212
TI  - Analysis of the risk and surgical stress for donors in living-related liver
      transplantation.

PMID- 10083213
TI  - Effect of intraportal infusion of adenosine on hepatic blood flow and injury
      after ischemia and reperfusion of canine liver.

PMID- 10083214
TI  - Late orthotopic liver retransplant: indications and survival. Liver Transplant
      Spanish Group.

PMID- 10083215
TI  - Domino liver transplantation for familial amyloid polyneuropathy: optimal use of
      a scarce resource.

PMID- 10083216
TI  - CD30+ and CD27- lymphocytes in liver transplant: Th2 cytokine secretion.

PMID- 10083217
TI  - Implication of Th1, Th2, and Th3 cytokines in liver graft acceptance.

PMID- 10083218
TI  - Successful cytokine treatment of aplastic anemia following living-related
      orthotopic liver transplantation for non-A, non-B, non-C hepatitis.

PMID- 10083219
TI  - Similar outcomes, morbidity, and mortality for orthotopic liver transplantation
      between the very elderly and the young.

PMID- 10083220
TI  - Humoral immunity in acute cellular rejection after living-donor liver
      transplantation.

PMID- 10083221
TI  - Auxiliary liver transplantation for urea-cycle enzyme deficiencies: lessons from
      three cases.

PMID- 10083222
TI  - Outcome of grafts procured in transplant patients.

PMID- 10083223
TI  - Increased risk for living liver donors after extended right lobectomy.

PMID- 10083224
TI  - Lamivudine prophylaxis in liver transplantation for hepatitis B in Asians.

PMID- 10083225
TI  - Selective hepatic denervation prior to organ harvest improves survival after
      liver transplantation.

PMID- 10083226
TI  - First experiences with mesh wrapping for parenchymal liver injuries in orthotopic
      liver transplantation.

PMID- 10083227
TI  - Transplantation of traumatized livers: is it safe?

PMID- 10083228
TI  - Liver retransplantation.

PMID- 10083229
TI  - Multiple sequential transplantation of hepatocytes in the Dalmatian dog model.

PMID- 10083230
TI  - Does elimination of Kupffer cells prolong survival time in liver transplantation?

PMID- 10083231
TI  - Why is a liver with steatosis susceptible to cold ischemic injury?

PMID- 10083232
TI  - Impact of donor liver microvesicular steatosis on the outcome of liver
      retransplantation.

PMID- 10083233
TI  - Prognostic value of crossmatch in liver transplantation.

PMID- 10083234
TI  - Good results of lamivudine in hepatitis B surface antigen-positive patients with
      active viral replication before liver transplantation.

PMID- 10083235
TI  - Orthotopic liver transplantation with and without peritoneal drainage: a
      comparative study.

PMID- 10083236
TI  - Apoptosis of hepatocytes is a main cause of inducing lethal hepatic failure after
      excessive hepatectomy in rats.

PMID- 10083237
TI  - Kupffer cell expression of CD40L (CD154) in human chronic liver allograft
      rejection.

PMID- 10083238
TI  - Immunomodulation of intestinal transplant with allograft irradiation and
      simultaneous donor bone marrow infusion.

PMID- 10083239
TI  - Early detection of the Fas-FasL system in hepatic graft-versus-host disease after
      rat small-bowel transplantation.

PMID- 10083240
TI  - Clinical outcome of intestinal transplantation at the University of Miami.

PMID- 10083241
TI  - Geranylgeranylacetone induces heat shock protein-73 in rat small intestine.

PMID- 10083242
TI  - Inhibition of nitric oxide synthesis reduces bacterial translocation during graft
      versus-host disease after small bowel transplantation.

PMID- 10083243
TI  - Translocation of bacteria from the gastrointestinal tract: protection afforded by
      lisofylline.

PMID- 10083244
TI  - Anti-rat OX-2 blocks increased small intestinal transplant survival after portal
      vein immunization.

PMID- 10083245
TI  - Characterization and modulation of preservation/reperfusion injury after small
      bowel transplantation.

PMID- 10083246
TI  - Evolution of clinical intestinal transplantation: improved outcome and cost
      effectiveness.

PMID- 10083247
TI  - Pretreatment of small bowel isograft donors with cobalt-protoporphyrin decreases
      preservation injury.

PMID- 10083248
TI  - Pathology and cell migration in a novel rat-to-mouse small bowel xenotransplant
      model.

PMID- 10083249
TI  - Prolonged small bowel allograft survival following repeated intrathymic
      injections of donor splenocytes and peripheral anti-lymphocyte treatment.

PMID- 10083250
TI  - Upregulation of basic fibroblast growth factor during chronic intestinal
      rejection.

PMID- 10083251
TI  - Mycophenolate mofetil/prednisolone/single-shot ATG with tacrolimus or
      cyclosporine in pancreas/kidney transplantation: first results of an ongoing
      prospective randomized trial.

PMID- 10083252
TI  - Morphologic features of large bowel biopsies in combined small and large bowel
      transplantations could predict clinical rejection.

PMID- 10083253
TI  - Report from the International Pancreas Transplant Registry--1998.

PMID- 10083254
TI  - Vascular graft thrombosis after pancreas transplantation: comparison of the FK
      506 and cyclosporine eras.

PMID- 10083255
TI  - MRI is superior to angiography for evaluation of living-related simultaneous
      pancreas and kidney donors.

PMID- 10083256
TI  - Surgical complications requiring early relaparotomy after pancreas
      transplantation: comparison of the cyclosporine and FK 506 eras.

PMID- 10083257
TI  - Long-term outcome in simultaneous kidney and pancreas transplant recipients with
      functioning allografts at 1-year posttransplantation.

PMID- 10083258
TI  - Utilization of pediatric donors for pancreas transplantation.

PMID- 10083259
TI  - Potential use of marginal donors for pancreas transplantation.

PMID- 10083260
TI  - Chronic pancreas allograft rejection: morphologic evidence of progression in
      needle biopsies and proposal of a grading scheme.

PMID- 10083261
TI  - Single-center experience of 60 consecutive simultaneous pancreas-kidney
      transplants using mycophenolate mofetil and tacrolimus as primary maintenance
      immunotherapy.

PMID- 10083262
TI  - Surgical complications after pancreas transplantation with portal-enteric
      drainage.

PMID- 10083263
TI  - Optimal immunosuppression in pancreas transplantation.

PMID- 10083264
TI  - Role of Fas in recurrence of autoimmune diabetes after islet transplantation.

PMID- 10083265
TI  - Anergic cells generated in vitro suppress rejection response to islet allografts.

PMID- 10083266
TI  - Acceptance of islet allografts transplanted with Fas ligand expressing testicular
      allografts.

PMID- 10083267
TI  - Local production of CTLA4-Ig by adenoviral-mediated gene transfer to the pancreas
      induces permanent allograft survival and donor-specific tolerance.

PMID- 10083268
TI  - Blockade of CD40L/CD40 costimulatory pathway in a DST presensitization model of
      islet allograft leads to a state of Allo-Ag specific tolerance and permits
      subsequent engraftment of donor strain islet or heart allografts.

PMID- 10083269
TI  - Induction of islet transplantation tolerance using donor specific transfusion and
      anti-CD154 monoclonal antibody.

PMID- 10083270
TI  - An improved technique for isolating pig islets: the importance of tensegrity in
      islet long-term culture viability.

PMID- 10083271
TI  - Synergy of class I and class II MHC deficiency (C1D and C2D) islets and early
      short-term suppression in achieving long-term islet graft survival and tolerance
      induction.

PMID- 10083272
TI  - Reversal of naturally occurring insulinopenic diabetes and induction of isolated
      islet xenograft tolerance in a preclinical study.

PMID- 10083273
TI  - Graft-versus-host disease and function of intrahepatic islet grafts.

PMID- 10083274
TI  - Chimerism-induced remission of overt diabetes in nonobese diabetic mice.

PMID- 10083275
TI  - Reversal of diabetes in streptozotocin-treated rats by intramuscular injection of
      recombinant adeno-associated virus containing rat preproinsulin II gene.

PMID- 10083276
TI  - Heart rate variability and quality of life following kidney and pancreas-kidney
      transplantation.

PMID- 10083277
TI  - Islet allografts: rejection and tolerance induction.

PMID- 10083278
TI  - Prolonged survival of islet allografts following combined therapy with tacrolimus
      and leflunomide.

PMID- 10083279
TI  - Analysis of the in vivo and in vitro response of human T cells to porcine islets.

PMID- 10083280
TI  - Quality assessment of isolated pancreatic rat islets by high-resolution
      respirometry.

PMID- 10083281
TI  - Analysis of passenger cell composition of human fetal pancreas: implications for
      transplantation.

PMID- 10083282
TI  - Pregnancy outcomes in female pancreas-kidney recipients.

PMID- 10083283
TI  - Regenerative signals for tissue-engineered small intestine.

PMID- 10083284
TI  - Anastomosis between tissue-engineered intestine and native small bowel.

PMID- 10083285
TI  - Cyclosporine A stimulates proliferation of vascular smooth muscle cells and
      enhances monocyte adhesion to vascular smooth muscle cells.

PMID- 10083286
TI  - Characterization of porcine dendritic cells grown in vitro.

PMID- 10083287
TI  - Enzyme release in hybrid liver support systems: marker for quality prior to
      clinical application.

PMID- 10083288
TI  - Fetal pig endocrine cells develop when allografted into the thymus gland.

PMID- 10083289
TI  - Apoptosis by gel-entrapped hepatocytes in a bioartificial liver.

PMID- 10083290
TI  - Mixed hematopoietic chimerism after hematopoietic stem cell allografts.

PMID- 10083291
TI  - Donor bone marrow, chimerism, histocompatibility and renal allograft rejection.

PMID- 10083292
TI  - Role of peripheral clonal deletion in tolerance induction with bone marrow
      transplantation and costimulatory blockade.

PMID- 10083293
TI  - Stem cell transplants in utero for genetic diseases: treatment and a model for
      induction of immunologic tolerance.

PMID- 10083294
TI  - The role of atypical T cells and NK cells in inhibiting primary engraftment of
      xenogeneic donor rat bone marrow cells.

PMID- 10083295
TI  - Pathogenic specificity of effector T lymphocytes in syngeneic graft-versus-host
      disease.

PMID- 10083296
TI  - Development of models of graft vascular disease in nonhuman primates: evaluation
      of GVD by intravascular ultrasound in a new cynomolgus model with arterial
      allograft exchange.

PMID- 10083297
TI  - Immune tolerance to self-MHC class II antigens after bone marrow transplantation.

PMID- 10083298
TI  - Reversal of diabetes in the rat by injection of hematopoietic stem cells infected
      with recombinant adeno-associated virus containing the preproinsulin II gene.

PMID- 10083299
TI  - Successful limb transplantation across a multi-minor barrier facilitated by
      preceding engraftment of T-cell-purged donor and recipient bone marrow.

PMID- 10083300
TI  - Augmentation of microchimerism with donor bone marrow infusion in hamster-to-rat
      heart xenograft recipients.

PMID- 10083301
TI  - Requirement of stromal cells in the bone marrow transplant for rapid lymphoid
      replenishment.

PMID- 10083302
TI  - Immune modulation in organ allograft recipients by single or multiple donor bone
      marrow infusions.

PMID- 10083303
TI  - Tolerance in Mlsa mismatched chimeras prepared with allogeneic bone marrow alone
      or in combination with syngeneic bone marrow.

PMID- 10083304
TI  - Chimeric liver established by recipient type bone marrow cell transplantation to
      donor before to liver transplantation produces marked suppression of allograft
      rejection in rats.

PMID- 10083305
TI  - Expression of human decay accelerating factor on cultured bone marrow cells from
      transgenic pigs.

PMID- 10083306
TI  - MHC structure and function.

PMID- 10083307
TI  - Is HLA matching worth the effort? Collaborative Transplant Study.

PMID- 10083308
TI  - Only a limited set of HLA epitopes is associated with organ graft loss.

PMID- 10083309
TI  - Role of HLA-G in maternal-fetal immune tolerance.

PMID- 10083310
TI  - Transfer of HLA antigens from stimulatory B cells to alloreactive T lymphocytes:
      a novel mechanism of "allospecific" autoregulation.

PMID- 10083311
TI  - Inhibition of transplant vasculopathy is associated with attenuated host allo
      antibody response.

PMID- 10083312
TI  - The role of beta-pleated sheet DRB1 differences in acute rejection after
      cadaveric renal transplant.

PMID- 10083313
TI  - Cytokine gene polymorphisms and relevance to forms of rejection.

PMID- 10083314
TI  - Nitric oxide upregulates HLA-DR in human vascular endothelial cells.

PMID- 10083315
TI  - Allocation of cadaver kidneys according to HLA-DR matching alone would result in
      optimal graft outcome in most recipients.

PMID- 10083316
TI  - Expression of soluble allo-MHC class I antigen in vivo suppresses IL-2 production
      by allo-reactive helper T cells.

PMID- 10083317
TI  - Transplantation without maintenance corticosteroids in 1-haplotype and 2
      haplotype HLA matched living-related renal transplant recipients treated with
      mycophenolate mofetil and cyclosporine.

PMID- 10083318
TI  - Pretransplant MLC in the presence of cyclosporine may predict renal allograft
      survival.

PMID- 10083319
TI  - Acquired tolerance is induced by MHC-incompatible test skin graft in adult
      thymectomized rats with chronic drainage of thoracic duct.

PMID- 10083320
TI  - A composite graft of islet plus donor lymph node cells induced donor specific
      tolerance in a "low responder" rat combination with class I MHC disparity.

PMID- 10083321
TI  - Correlation of pretransplant allosensitization with severity of rejection biopsy.

PMID- 10083322
TI  - On/off switching Fas-ligand gene expression in liver by Cre/Loxp adenovirus
      vector system.

PMID- 10083323
TI  - Genetic polymorphism in the IL-10 promoter region in renal transplantation.

PMID- 10083324
TI  - Development of anti-HLA-antibodies against intra-CREG-mismatches in renal
      transplant recipients.

PMID- 10083325
TI  - Regulation of immune reactivity and tolerance by antigen migration and
      localization: with particular reference to allo- and xenotransplantation.

PMID- 10083326
TI  - T-cell activation pathways: a transplantation perspective.

PMID- 10083327
TI  - Positive and negative signaling pathways.

PMID- 10083328
TI  - TNF alpha and CD95-L contribute to apoptosis of activated lymphocytes triggered
      by ATGs.

PMID- 10083329
TI  - Specific inhibition of CD26/DPP IV enzymatic activity in allograft recipients:
      effects on humoral immunity.

PMID- 10083330
TI  - The 2C T-cell transgenic mouse: an in vivo model of allospecific cytotoxic T-cell
      activation and homing.

PMID- 10083331
TI  - Reduced transcription factor binding at the IL-2 promoter region in anergized
      human CD4+ T lymphocytes.

PMID- 10083332
TI  - Class I peptides involved in the indirect pathway of allorecognition.

PMID- 10083333
TI  - Increased IL-4 production and decreased CD40L expression by newborn T cells
      contribute to transplantation tolerance.

PMID- 10083334
TI  - Hepatocytes and liver nonparenchymal cells induce apoptosis in activated T cells.

PMID- 10083335
TI  - Involvement of protein tyrosine phosphorylation in immunotoxin effects on T
      lymphocytes.

PMID- 10083336
TI  - Different roles for alpha 4-integrin/VCAM-1 and alpha 4/fibronectin interactions
      in allograft rejection.

PMID- 10083337
TI  - Donor antigen-independent effector mechanisms of graft rejection: a novel cell
      surface target of IL-2-activated natural killer cells.

PMID- 10083338
TI  - Adenovirus-mediated gene transfer of the anti-apoptotic protein A20 in rodent
      islets inhibits IL-1 beta-induced NO release.

PMID- 10083339
TI  - Targeted gene transfer to sinusoidal endothelial cells and expression in vivo.

PMID- 10083340
TI  - Construction of a recombinant adenovirus vector encoding Fas ligand with a
      CRE/Loxp inducible system.

PMID- 10083341
TI  - Comparison of viral gene-deleted adenoviral vectors with the E1-deleted
      adenoviral vector in islets.

PMID- 10083342
TI  - Adhesion molecules, their receptors, and their regulation: analysis of CD6
      activated leukocyte cell adhesion molecule (ALCAM/CD166) interactions.

PMID- 10083343
TI  - Transduction of dendritic cells with adenoviral vectors encoding CTLA4-Ig
      markedly reduces their allostimulatory activity.

PMID- 10083344
TI  - Chimerism in transplantation and in spontaneously occurring autoimmune disease.

PMID- 10083345
TI  - Microchimerism analysis using polymerase chain reaction assays that selectively
      amplify donor DNA.

PMID- 10083346
TI  - Thymic-independent peripheral tolerance.

PMID- 10083347
TI  - Inhibition of iNOS induction by FK506, but not by cyclosporine, in rat
      hepatocytes.

PMID- 10083348
TI  - Macrophages--but not T-cell--derived cytokines stimulate endothelin-1 secretion
      by endothelial cells.

PMID- 10083349
TI  - Cytosolic calcium dynamics and free radical-induced apoptosis of the endothelial
      cells.

PMID- 10083350
TI  - Regulation of smooth muscle cell proliferation and migration.

PMID- 10083351
TI  - Secretion and storage of insulin from a human hepatoma cell line (HUH7-INS).

PMID- 10083352
TI  - Role of graft cytokine expression in the tolerogenicity of neonatal skin
      allografts.

PMID- 10083353
TI  - Single-cell analysis of T-cell responses in vitro and in vivo: role of
      costimulatory signals.

PMID- 10083354
TI  - Antithrombin III inhibits T- and B-lymphocyte activation in vitro and improves
      parameters of inflammation in a rat model of acute lung allograft rejection.

PMID- 10083355
TI  - Decreased gamma-IFN and IL-2 gene expression in regional lymph nodes of skin
      allografts is associated with increased allograft survival in the WKY F344 rat
      model.

PMID- 10083356
TI  - Down-modulation of IL-2-triggered JAK3-STAT5 signaling following CD4-ligand
      binding.

PMID- 10083357
TI  - Attenuation of IL-2 receptor signaling by CD4-ligation requires polymerized
      cytoskeletal actin but not P56LCK.

PMID- 10083358
TI  - Cytotoxic sinusoidal lymphocytes of liver transplant are effective against
      circulating tumor cells.

PMID- 10083359
TI  - Statins inhibit T-cell interactions with elastin.

PMID- 10083360
TI  - T cell-mediated effector mechanisms in the rejection of allogeneically
      transplanted hepatocytes.

PMID- 10083361
TI  - B lymphocytes influence the shape of the mature preimmune CD4+ TCR repertoire.

PMID- 10083362
TI  - In vivo MLR: a novel method for the study of alloimmune responses.

PMID- 10083363
TI  - Characterization of the alloimmune response to minor histocompatibility antigens
      by in vivo MLR.

PMID- 10083364
TI  - Induction of tolerance to an "untolerizable" strain by double-strain intrathymic
      inoculation in experimental rat cardiac transplantation.

PMID- 10083365
TI  - Tolerance of rat cardiac allografts does not require donor-type "passenger"
      antigen presenting cells.

PMID- 10083366
TI  - Indirect allorecognition is involved in both acute and chronic allograft
      rejection.

PMID- 10083367
TI  - Direct allorecognition: a mechanism in intrathymic tolerance induction.

PMID- 10083368
TI  - Mechanisms underlying the development of T-cell tolerance following interruption
      of signalling at the CD28/B7 and CD40/gp39 interface.

PMID- 10083369
TI  - Study of donor-specific antigens in inducing tolerance and enhancing graft
      survival.

PMID- 10083370
TI  - Antithrombin III inhibits T and B lymphocyte activation in vitro and improves
      parameters of inflammation in a rat model of acute lung allograft rejection.

PMID- 10083371
TI  - Malononitrilamides prevent the generation of oxygen radicals in mononuclear
      phagocytes and graft rejection in a rat model.

PMID- 10083372
TI  - Effect of hepatocyte growth factor on chronic rejection in rat renal allografts.

PMID- 10083373
TI  - Hepatic mononuclear cells modulate delivery of immunogenic stimuli by allogeneic
      dendritic cells.

PMID- 10083374
TI  - A novel function for A20 in smooth muscle cells: inhibition of activation and
      proliferation.

PMID- 10083375
TI  - Kinetics and significance of graft tissue nitric oxide after rat and mouse liver
      transplantation.

PMID- 10083376
TI  - Vascular smooth muscle cells express VCAM-1 and embryonic myosin isoforms in
      transplant arteriopathy.

PMID- 10083377
TI  - CD8+ cytotoxic T lymphocytes are involved in inducing medial cell dropout via
      apoptosis in mouse aortic allografts.

PMID- 10083378
TI  - Prevention of cardiac allograft arteriopathy by antisense Cdc2 kinase
      oligonucleotide.

PMID- 10083379
TI  - Systemic hypertension accelerates chronic rejection of renal allografts in the
      rat.

PMID- 10083380
TI  - Effects of peritransplant administration of hematopoietic growth factors on the
      development of chronic allograft rejection.

PMID- 10083381
TI  - Rescue effect of FTY720 on acute renal rejection in dogs.

PMID- 10083382
TI  - CD26/DPP IV-mediated modulation of acute rejection.

PMID- 10083383
TI  - Acute rejection of rat renal allografts is accelerated by donor brain death.

PMID- 10083384
TI  - Distinct tolerance pathways in sensitized rat recipients after blockade of
      activation signal 1 and signal 2.

PMID- 10083385
TI  - Induction and maintenance of tolerance by CTLA-4IG in rat small bowel allografts.

PMID- 10083386
TI  - Use of gene therapy for tolerogenic signals.

PMID- 10083387
TI  - Prolonged skin allograft survival in mice treated with Flt3-ligand-induced
      dendritic cells and anti-CD154 monoclonal antibody.

PMID- 10083388
TI  - Haematopoietic stem cells transduced with a single donor class I major
      histocompatibility complex gene can induce operational tolerance to fully
      allogeneic cardiac allografts.

PMID- 10083389
TI  - Depletion of IL-4 does not prevent tolerance induction in an allogeneic rat
      kidney transplantation model.

PMID- 10083390
TI  - Burns and skin transplantation.

PMID- 10083391
TI  - Rejection of discordant skin xenografts by CD4- CD8- TCR alpha beta+ cells in CD4
      and CD8-deficient mice.

PMID- 10083392
TI  - Oral administration of alloantigen induces indefinite prolongation of MHC
      mismatched cardiac allografts.

PMID- 10083393
TI  - Biological factors that affect CD95 ligand-mediated inflammation.

PMID- 10083394
TI  - Involvement of Th1 subset in allogeneic keratinocyte rejection.

PMID- 10083395
TI  - Maintenance of acquired thymic tolerance to rat islet allografts by
      regulatory/suppressor T cells.

PMID- 10083396
TI  - Lack of pluripotent stem cell engraftment in cyclophosphamide-induced tolerance.

PMID- 10083397
TI  - TAP1 mutant mice reject heart grafts from donors with no MHC disparity.

PMID- 10083398
TI  - Physiologic incompatibilities in discordant xenotransplantation.
AB  - At present, several incompatibilities between pig and human, not only from the
      immunologic point of view but also regarding physiological and molecular systems,
      have been identified. It is anticipated that this is only the tip of the iceberg
      regarding this topic. However, there are also many systems that are compatible.
      Strategies have been outlined, and many tools, such as gene modification, are
      available to solve the problems. Therefore, the statement by Keith Reemtsma in
      the foreward to the latest issue of the monography Xenotransplantation "The
      important question is not whether xenotransplantation will succeed, but rather
      how and under what circumstances xenografts will provide predictable enough
      results to warrent clinical application" will hopefully be a reality in the
      future.

PMID- 10083399
TI  - Xenotransplantation: the potential for xenogeneic infections.

PMID- 10083400
TI  - The role of cytokines in rejection of discordant xenotransplants.

PMID- 10083402
TI  - Evaluation of porcine cytomegalovirus as a potential zoonotic agent in
      xenotransplantation.

PMID- 10083401
TI  - Porcine endogenous retrovirus is transmitted neither in vivo nor in vitro from
      porcine endothelial cells to baboons.

PMID- 10083403
TI  - Human cytolytic T lymphocyte recognition of miniature swine xenoantigens.

PMID- 10083404
TI  - Analysis of T cell repertoire in a concordant hamster-to-rat cardiac xenograft
      model during accommodation and rejection process.

PMID- 10083405
TI  - Functional relevance of donor-derived hematopoietic microchimerism only for
      induction but not for maintenance of allograft acceptance.

PMID- 10083406
TI  - Transplantation-associated Kaposi's sarcoma: herpesvirus 8 transmission through
      renal allografts.

PMID- 10083407
TI  - Porcine thymus supports development of human T cells that are tolerant to porcine
      xenoantigens.

PMID- 10083408
TI  - Pretreatment of islets with mitomycin C and blockage of costimulatory signal
      induces unresponsiveness to islet xenografts.

PMID- 10083409
TI  - Characteristics of B lymphocyte and natural killer cell xenotolerance in a
      concordant hamster-to-athymic rat cardiac xenotransplantation model.

PMID- 10083410
TI  - Cloning of the porcine costimulatory molecule CD40.

PMID- 10083411
TI  - Preferred T-cell receptor V beta usage in the xenogeneic human antiporcine
      cytolytic response.

PMID- 10083412
TI  - Prolonged pulmonary xenograft survival: tissue infiltration compared with
      infiltration in the bronchoalveolar space.

PMID- 10083413
TI  - Prolongation of ex vivo-perfused pig xenograft survival by the complement
      inhibitor Compstatin.

PMID- 10083414
TI  - Review of allo- and xenogeneic neural grafts in neurodegenerative disorders.
      Neural Tissue Transplantation Team(NETTLU).

PMID- 10083415
TI  - Transplanted hepatocytes infected with a complement receptor type 1 (CR1)
      containing recombinant adenovirus are resistant to hyperacute rejection.

PMID- 10083416
TI  - Significance of anti-Gal IgG in chronic xenograft rejection.

PMID- 10083417
TI  - Significance of histochemical expression of Hanganutziu-Deicher antigens in pig,
      baboon and human tissues.

PMID- 10083418
TI  - Reduction of anti-Gal alpha 1-3Gal natural antibodies in sera of alpha 1,3
      galactosyltransferase-deficient mice receiving Gal-positive bone marrow
      transplantation.

PMID- 10083419
TI  - Sustained decrease of serum anti-galactose alpha 1-3-galactose antibodies in
      baboons by removing aerobic gram-negative bacteria from the bowel.

PMID- 10083420
TI  - Ultrastructural localization of Gal alpha 1-3Gal in the pig kidney.

PMID- 10083421
TI  - Prolongation of cardiac allograft survival with intracoronary viral interleukin
      10 gene transfer.

PMID- 10083422
TI  - HLA-G expression protects porcine endothelial cells from xenogeneic cytotoxicity
      mediated by human natural killer cells.

PMID- 10083423
TI  - Antisense Cdc2 kinase oligonucleotide inhibits adhesion molecule expression in
      cardiac allograft arteriopathy.

PMID- 10083424
TI  - Xenogeneic thymic transplantation in a pig-to-nonhuman primate model.

PMID- 10083425
TI  - Three-month survival of HDAFF transgenic pig hearts transplanted into primates.

PMID- 10083426
TI  - Rejection of hamster cardiac xenografts by rat CD4+ or CD8+ T cells.

PMID- 10083427
TI  - Splenectomy improves survival of HDAF transgenic pig kidneys in primates.

PMID- 10083428
TI  - Long-term (10-month) pig islet xenograft tolerance using measured total lymphoid
      irradiation, splenectomy, short-term rabbit antithymocyte globulin, and
      deoxyspergualin without long-term immunosuppression.

PMID- 10083429
TI  - Characterization of xenograft resistance to autoimmune disease recurrence after
      pancreas islet transplantation.

PMID- 10083430
TI  - Operational tolerance of long-surviving cardiac xenografts (LSCX) is related to
      modification of the graft-in-residence and not to induced tolerance in the
      recipient: studies in retransplanted LSCX.

PMID- 10083431
TI  - Generation and characterization of xenospecific human suppressor T cells.

PMID- 10083432
TI  - Hyperacute rejection models: ex vivo xenoperfusion systems.

PMID- 10083433
TI  - Human decay accelerating factor transgenic pigs for xenotransplantation obtained
      by sperm-mediated gene transfer.

PMID- 10083434
TI  - Morphometric analyses to predict appropriate donor size for swine-to-human
      cardiac xenotransplantation.

PMID- 10083435
TI  - Rat peripheral T-cell receptor V beta repertoire in F344-to-B10 (rat-to-mouse)
      mixed xenogeneic chimeras.

PMID- 10083436
TI  - Possible defect of SCID M phi/DC in acquired tolerance induction following rat
      into SCID xenogeneic bone marrow cell chimeras.

PMID- 10083437
TI  - FK 506 prevents islet xenograft rejection: a study in the pig-to-rat model.

PMID- 10083438
TI  - Influence of cryopreservation on antigen expression and immunogenicity of human
      vascular endothelial cells.

PMID- 10083439
TI  - Does cold ischemia induce chronic kidney transplant dysfunction?

PMID- 10083440
TI  - Effect of anoxia on expression of endothelial leukocyte adhesion molecule 1 in
      cultured human endothelial cells.

PMID- 10083441
TI  - Estimation of mitochondrial damage in heart preservation.

PMID- 10083442
TI  - Does H2O2-mediated oxidative stress reproduce mitochondrial cold
      preservation/reoxygenation injury in endothelial cells?

PMID- 10083443
TI  - Mitochondrial defect in endothelial cold ischemia/reperfusion injury.

PMID- 10083444
TI  - Protective effect of JTV519 (K201), a new 1,4-benzothiazepine derivative, on
      prolonged myocardial preservation.

PMID- 10083445
TI  - Physiologic changes following brain death.

PMID- 10083446
TI  - Activation of proinflammatory genes in somatic organs as a consequence of brain
      death.

PMID- 10083447
TI  - Induction of organ dysfunction and activation of inflammatory markers in donor
      liver and kidney during hypotensive brain death.

PMID- 10083448
TI  - Donor brain death affects tempo and intensity of acute rejection of rat chronic
      allografts.

PMID- 10083449
TI  - FR167653 ameliorates pulmonary ischemia-reperfusion injury.

PMID- 10083450
TI  - Genetic cytoprotection of human endothelial cells during preservation time with
      an adenoviral vector encoding the anti-apoptotic human Bcl-2 gene.

PMID- 10083451
TI  - Cytoprotective role of antioxidant stress protein induced by adenosine A1
      receptor antagonist in rat heart ischemic injury.

PMID- 10083452
TI  - Glutamine-induced heme oxygenase-1 protects intestines and hearts from warm
      ischemic injury.

PMID- 10083453
TI  - Demonstration of nitric oxide generation during renal ischemia reperfusion injury
      using paramagnetic resonance spectroscopy.

PMID- 10083454
TI  - Nitric oxide donor induces upregulation of stress proteins in cold ischemic rat
      hearts.

PMID- 10083455
TI  - SDZ RAD inhibits cold ischemia-induced vascular remodeling.

PMID- 10083456
TI  - Donor treatment with mycophenolate mofetil protects against ischemia-reperfusion
      injury.

PMID- 10083457
TI  - Effect of intraportal infusion of adenosine on hepatic blood flow and injury
      after ischemia and reperfusion of canine liver.

PMID- 10083458
TI  - Reduction of reperfusion injury with prostacyclin I2 after liver transplantation.

PMID- 10083459
TI  - Effective protection against prolonged warm ischemia of rat kidney using a simple
      preservation solution.

PMID- 10083460
TI  - Pyruvate inhibits the chronic damage which ensues after ischemia/reperfusion
      injury of kidneys.

PMID- 10083461
TI  - Expression of heat shock proteins 60 and 70 is a marker of preservation-induced
      endothelial cell activation.

PMID- 10083462
TI  - Does "second warm ischemia time" play a role in kidney allograft function?

PMID- 10083463
TI  - Hospital professionalization of the organ procurement process maximizes the
      retrieval potential.

PMID- 10083464
TI  - Organ exchange organization: public or private? The French example.

PMID- 10083465
TI  - Regulation, legislation, and organization of cadaveric organ procurement.

PMID- 10083466
TI  - Cardiac preservation with nitroglycerine and cyclic adenosine monophosphate.

PMID- 10083467
TI  - Effectiveness of ischemic preconditioning on long-term myocardial preservation.

PMID- 10083468
TI  - Intraoperative reperfusion blood flow predicts post warm ischemic kidney
      transplant survival and efficacy of preservation maneuvers.

PMID- 10083469
TI  - Effects of leukocyte depleted blood on renal reperfusion injury in a porcine
      model.

PMID- 10083470
TI  - Gender influences cold preservation-reoxygenation injury in the liver.

PMID- 10083471
TI  - Protective effect of monoclonal antibodies to adhesion molecules on rat liver
      ischemia-reperfusion injury.

PMID- 10083472
TI  - Kupffer's cells modulate neutrophile activity by superoxide anion and tumor
      necrosis factor-delta in reperfusion injury of liver transplantation-mechanisms
      of radical generation and reperfusion injury after cold ischemia.

PMID- 10083473
TI  - Sodium salicylate protects hepatocytes but not endothelial cells during
      reperfusion after cold ischemia.

PMID- 10083474
TI  - Inhibition of thromboxane A2 synthesis by OKY-046 attenuates ischemia and
      reperfusion injury of the liver.

PMID- 10083475
TI  - S-adenosyl L-methionine effect on hepatic allografts procured from non-heart
      beating donor pigs.

PMID- 10083476
TI  - Nitric oxide enhancement attenuates ischemia and reperfusion injury of canine
      livers.

PMID- 10083477
TI  - Preservation of livers from non-heart-beating donors: modulation of cAMP signal
      and organ viability by glucagon.

PMID- 10083478
TI  - L-arginine during liver procurement from non-heart-beating donor pigs:
      histological evaluation.

PMID- 10083479
TI  - The evolution of organ transplantation in the Middle East.

PMID- 10083480
TI  - A new portable hypothermic perfusion apparatus for long-term heart preservation
      in canine models.

PMID- 10083481
TI  - Histomorphological analysis of preservation injury as determinant of graft
      quality in clinical liver transplantation.

PMID- 10083482
TI  - JNK activation and apoptosis during ischemia-reperfusion.

PMID- 10083483
TI  - Fructose protects rat hepatocytes against hypoxic injury during the process of
      isolation and microencapsulation.

PMID- 10083484
TI  - Donor action in Spain: a program to increase organ donation.

PMID- 10083485
TI  - Impact of school-based teaching on students' opinions of organ donation and
      transplantation.

PMID- 10083486
TI  - Preservation with a retrograde second flushing of Eurocollins in clinical lung
      transplantation.

PMID- 10083487
TI  - Microcirculatory disturbance is an obstacle to liver transplantation from agonal
      NHBD.

PMID- 10083488
TI  - Protective effect of JTV519 on prolonged myocardial preservation.

PMID- 10083489
TI  - Rational design of new immunosuppressive drugs.

PMID- 10083490
TI  - Compliance in pediatric solid organ transplantation.

PMID- 10083491
TI  - Induction protocols: yesterday, today, and tomorrow.

PMID- 10083492
TI  - Optimal long-term immunotherapy protocols.

PMID- 10083493
TI  - Clinical trial potential of academic centers in India.

PMID- 10083494
TI  - Withdrawal versus continuous cyclosporine therapy in kidney transplant recipients
      of one-haplotype-matched donors.

PMID- 10083495
TI  - Oral delivery of liposomal tacrolimus: increased efficacy and reduced toxicity.

PMID- 10083496
TI  - Long-term results and risk factors of quadruple immunosuppression in renal
      transplantation.

PMID- 10083497
TI  - Mycophenolate mofetil in combination with tacrolimus versus Neoral after liver
      transplantation.

PMID- 10083498
TI  - IMPDH activity in whole blood and isolated blood cell fraction for monitoring of
      CellCept-mediated immunosuppression.

PMID- 10083499
TI  - Management of nephrotoxic drugs.

PMID- 10083500
TI  - Are renal transplant recipients on CsA-based immunosuppressive regimens more
      likely to develop skin cancer than those on azathioprine and prednisolone?

PMID- 10083501
TI  - Tacrolimus/"low-dose" mycophenolate mofetil versus microemulsion
      cyclosporine/"low-dose" mycophenolate mofetil after kidney transplantation--1
      year follow-up of a prospective, randomized clinical trial.

PMID- 10083502
TI  - A comparative study of 500 mg BID and 250 mg BID of prophylactic oral ganciclovir
      in post-kidney transplant "CMV at risk" recipients.

PMID- 10083503
TI  - Mechanisms of cyclosporine-induced nephrotoxicity.

PMID- 10083504
TI  - The effect of cyclosporine vs FK 506 on glucose metabolism.

PMID- 10083505
TI  - Improved outcome of steroid withdrawal in mycophenolate mofetil-treated primary
      cadaveric renal transplant recipients.

PMID- 10083506
TI  - Mycophenolate mofetil in living donor renal allograft recipients.

PMID- 10083507
TI  - A prospective, randomized trial of tacrolimus/prednisone vs
      tacrolimus/prednisone/mycophenolate mofetil in renal transplantation: 1-year
      actuarial follow-up.

PMID- 10083508
TI  - Overestimation of mycophenolic acid by EMIT correlates with MPA metabolite.

PMID- 10083509
TI  - Usefulness of 15-deoxyspergualin for rejection in renal transplantation.

PMID- 10083510
TI  - Analysis of cost-effectiveness and cost-utility for immunosuppressive protocols
      in renal transplantation.

PMID- 10083511
TI  - Nonnephrotoxic, nonatherogenic maintenance therapy in kidney-transplanted
      patients using MMF-monotherapy: a pilot study.

PMID- 10083512
TI  - Triple therapy with mycophenolate mofetil versus azathioprine.

PMID- 10083513
TI  - Immunosuppression with FK 506 does not improve kidney graft survival.
      Collaborative Transplant Study.

PMID- 10083514
TI  - Is azathioprine harmful to chronic viral hepatitis in renal transplantation? A
      long-term study on azathioprine withdrawal.

PMID- 10083515
TI  - Low-dose tacrolimus (FK 506)-based immunosuppressive protocol in living donor
      renal transplantation.

PMID- 10083516
TI  - Excellent long-term survival of low-risk, first renal allografts using
      cyclosporine/azathioprine double therapy.

PMID- 10083517
TI  - Immunosuppressive action of FTY720 for renal allograft a rat model.

PMID- 10083518
TI  - Benefit of mycophenolate mofetil in patients with cyclosporine A-induced
      nephropathy after lung transplantation.

PMID- 10083519
TI  - Mycophenolate mofetil/Neoral/steroid vs Neoral/steroid therapy for prophylaxis of
      acute rejection in renal transplant recipients.

PMID- 10083520
TI  - Identification of a high molecular weight enzyme component in crude C
      histolyticum collagenase that is essential for the appropriate disaggregation of
      the pig and human pancreas.

PMID- 10083521
TI  - Comparison of MPA trough levels in patients with severe diabetes mellitus and
      from non-diabetics after transplantation.

PMID- 10083522
TI  - Chronic rejection in cyclosporin A treated renal allograft recipients with
      allopeptide reactive T cells.

PMID- 10083523
TI  - The effect of cyclosporin A and tacrolimus on cultured human epithelial cells:
      the role of TGF-beta.

PMID- 10083524
TI  - HP12: a highly purified Helleborus species extract strongly potentiates the T
      cell suppressive effect of cyclosporine A.

PMID- 10083525
TI  - Mycophenolic acid inhibits PDGF-induced osteopontin expression in rat mesangial
      cells.

PMID- 10083526
TI  - Effect of a novel immunosuppressant, FTY720, on heart and liver transplantations
      in rats.

PMID- 10083527
TI  - Cyclosporine, but not FK506 and rapamycin, enhances Na(+)-K(+)-CL- cotransport
      activity in cultured medullary thick ascending limb cells.

PMID- 10083528
TI  - Daclizumab rapidly saturates interleukin-2 receptor-alpha (CD25) on lymph node
      lymphocytes in children.

PMID- 10083529
TI  - Coadministration of malononitrilamides and tacrolimus induces tolerance in a rat
      skin allograft model.

PMID- 10083530
TI  - Modulation of alloimmunity with class I MHC peptides: mechanisms of action.

PMID- 10083531
TI  - HLA-G mediates protection from natural killer cytolysis: implications in immune
      tolerance.

PMID- 10083532
TI  - Gene transfer of immunosuppressive peptides B2702 and RDP1257 prolongs allograft
      survival: evidence suggesting a role for heme oxygenase-I.

PMID- 10083533
TI  - Enhancement of dendritic cell tolerogenicity by genetic modification using
      adenoviral vectors encoding cDNA for TGF beta 1.

PMID- 10083534
TI  - Extension of graft survival with pulsed administration of donor dendritic cells.

PMID- 10083535
TI  - The combined use of sublethal irradiation and costimulatory blockade to generate
      mixed bone marrow chimeras.

PMID- 10083536
TI  - Allogeneic thymo-kidney transplants induce stable tolerance in miniature swine.

PMID- 10083537
TI  - New usage paradigms in antibody therapy: safety of the new agents.

PMID- 10083538
TI  - Inhibition of IL-10 by FK 506 may be responsible for overcoming ongoing allograft
      rejection in the rat.

PMID- 10083539
TI  - Effect of a new immunosuppressive agent, KF20444, in rat cardiac transplantation.

PMID- 10083540
TI  - Dose-dependent study of a novel immunosuppressant, FTY720, with the canine renal
      allograft transplantation model.

PMID- 10083541
TI  - Simulect (basiliximab) reduces acute cellular rejection in renal allografts from
      cadaveric and living donors.

PMID- 10083542
TI  - Determination of mycophenolic acid level: comparison of high-performance liquid
      chromatography with homogeneous enzyme-immunoassay.

PMID- 10083543
TI  - Acute rejection and the flow cytometry crossmatch.

PMID- 10083544
TI  - IL-10 is an effector molecule mediating urocanic acid-induced immunosuppression.

PMID- 10083545
TI  - Abolition of anti-CD4-induced allotransplantation tolerance by exogenous IL-2.

PMID- 10083546
TI  - Tamoxifen prolongs heart allograft survival in cyclosporine-treated female mice.

PMID- 10083547
TI  - FTY720, a novel immunosuppressant, shows a synergistic effect in combination with
      FK 506 in rat allograft models.

PMID- 10083548
TI  - FTY720, a novel immunosuppressant, prolongs rat skin allograft survival by
      decreasing T-cell infiltration into grafts.

PMID- 10083549
TI  - FTY720, a novel immunosuppressant, induces sequestration of circulating
      lymphocytes by acceleration of lymphocyte homing.

PMID- 10083550
TI  - New usage paradigms in antibody therapy: induction or true prophylaxis?

PMID- 10083551
TI  - Toward preclinical studies with anti-CD86 immunotoxin.

PMID- 10083552
TI  - Analysis of donor-specific unresponsiveness to rat allografts by nondepleting
      anti-CD4 monoclonal antibody (RIB 5/2) plus donor antigen.

PMID- 10083553
TI  - Differential effect of an anti-CD8 monoclonal antibody on rejection of murine
      intestine and cardiac allografts.

PMID- 10083554
TI  - Prevention of T-cell activation by rhCTLA4-Ig and anti-CD40L monoclonal antibody
      results in indefinite islet allograft survival.

PMID- 10083555
TI  - Systemic administration of CTLA4-Ig or anti-CD40 ligand antibody inhibits second
      set rejection of mouse liver allografts.

PMID- 10083556
TI  - Effects of anti-CD2 monoclonal antibody: CD2- and CD95-mediated apoptosis of
      human peripheral T cells.

PMID- 10083557
TI  - Can antibody prophylaxis allow sparing of other immunosuppressives?

PMID- 10083558
TI  - Endothelin-1 receptor blockade and its effect on chronic rejection.

PMID- 10083559
TI  - Mycophenolate mofetil impairs transendothelial migration of allogeneic CD4 and
      CD8 T-cells.

PMID- 10083560
TI  - Monitoring of CMV infection after renal transplantation: serology, culture, and
      viral DNA detection by hybrid capture.

PMID- 10083561
TI  - Rapid diagnosis of donor and renal allograft infection using a polymerase chain
      reaction technique.

PMID- 10083562
TI  - Posttransplant malignancies.

PMID- 10083563
TI  - Patterns of malignancies following renal transplantation.

PMID- 10083564
TI  - Risk of tumor transmission in transplantation from donors with primary brain
      tumors: an Australian and New Zealand registry report.

PMID- 10083565
TI  - Lymphoproliferative disease in children.

PMID- 10083566
TI  - Polymorphism and T-cell infiltration in posttransplant lymphoproliferative
      disorders.

PMID- 10083567
TI  - Cancer risk associated with ATG/OKT3 in renal transplantation.

PMID- 10083568
TI  - Hepatocellular carcinoma after kidney transplantation.

PMID- 10083569
TI  - Incidence and outcome of de novo malignancies after liver transplantation.

PMID- 10083570
TI  - Long-term metabolic complications.

PMID- 10083571
TI  - Hyperhomocysteinemia and other coronary risk factors in 20-year renal transplant
      recipients (level 5A) with and without coronary heart disease.

PMID- 10083572
TI  - Prolonged hypertension (> 10 years) is a significant risk factor in older cadaver
      donor renal transplants.

PMID- 10083573
TI  - Studies of erythroid burst-forming units in patients with posttransplant
      erythrocytosis.

PMID- 10083574
TI  - Chronic allograft nephropathy: effect of cyclosporine reduction and addition of
      mycophenolate mofetil on progression of renal disease.

PMID- 10083575
TI  - Prevention of chronic heart allograft rejection.

PMID- 10083576
TI  - Impact of delayed function on long-term graft survival after solid organ
      transplantation.

PMID- 10083577
TI  - Surrogate end points in chronic kidney graft rejection studies.

PMID- 10083578
TI  - Morphologic criteria of chronic renal allograft rejection.

PMID- 10083579
TI  - Contribution of donor age and ischemic injury in chronic renal allograft
      dysfunction.

PMID- 10083580
TI  - Predisposing factors in the development of chronic allograft dysfunction.

PMID- 10083581
TI  - The association between acute rejection and chronic rejection in kidney
      transplantation.

PMID- 10083582
TI  - Immunologic and nonimmunologic risk factors of chronic rejection.

PMID- 10083583
TI  - Chronic rejection of cadaveric renal allografts: role of acute rejection
      episodes.

PMID- 10083584
TI  - Graft outcome in patients with biopsy-proven chronic renal allograft rejection.

PMID- 10083585
TI  - Oxidative stress in renal transplant recipients with chronic rejection: rationale
      for antioxidant supplementation.

PMID- 10083586
TI  - Treatment of chronic renal allograft failure by addition of mycophenolate
      mofetil: single-center experience in 40 patients.

PMID- 10083587
TI  - Organ transplantation and the human revolution.

PMID- 10083588
TI  - The cost-effectiveness of transplantation with expanded donor kidneys.
AB  - Transplantation with EDKs is a cost-effective therapy for ESRD as compared to
      hemodialysis across a variety of clinical and financial scenarios. In many cases
      the costs of pursuing transplantation with these donors will exceed hospital
      reimbursement for the procedure, providing a financial disincentive to pursuing a
      clearly cost-effective therapy.

PMID- 10083589
TI  - Living renal donor health eligibility: a European "best practice" protocol?

PMID- 10083590
TI  - Informed consent from recipients of marginal donor organs.

PMID- 10083591
TI  - Profiles of noncompliance in patients with a functioning renal transplant: a
      multicenter study. Compliance Study Group.

PMID- 10083592
TI  - The economics of immunosuppression in renal transplantation: a review of recent
      literature.

PMID- 10083593
TI  - National and local forces in organ allocation.

PMID- 10083594
TI  - How dangerous are financial incentives to obtain organs?

PMID- 10083595
TI  - Ethical issues in pediatric liver transplantation.

PMID- 10083596
TI  - Cultural aspects of organ donation and transplantation.

PMID- 10083597
TI  - Race/ethnic-based opinions on organ donation and transplantation among teens:
      preliminary results.

PMID- 10083598
TI  - Professional attitudes to bioethical issues ration the supply of "marginal living
      donor" kidneys for transplantation.

PMID- 10083599
TI  - The development of chronic renal allograft rejection may be predicted early
      following transplantation.

PMID- 10083600
TI  - Use of a newly developed ultrasound contrast medium for color Doppler evaluation
      in kidney transplantation.

PMID- 10083601
TI  - Angiotensin converting enzyme gene polymorphism in renal transplant patients with
      IgA nephropathy: relationship with graft function and prevalence of hypertension.

PMID- 10083602
TI  - CD40 upregulation in TCR alpha/beta+ CD68+ cells and parenchymal CD40L induction
      and associated with NF-kappa B activation in chronic rejecting human renal
      allografts.

PMID- 10083603
TI  - CMV increases collagen synthesis in chronic rejection in rat renal allograft.

PMID- 10083604
TI  - Kidney recipient CMV incidence in the gancyclovir era: monitoring viral DNA by a
      CMV-PCR assay.

PMID- 10083605
TI  - Predictive indicators of rejection or infection in renal transplant patients.

PMID- 10083606
TI  - The incidence and management of osteoporosis, gout, and avascular necrosis in
      recipients of renal allografts functioning more than 20 years (level 5A) treated
      with prednisone and azathioprine.

PMID- 10083607
TI  - Cyclosporine and anti-CD3 blockade of lymphocyte apoptosis induced by
      cytomegalovirus antigens.

PMID- 10083608
TI  - Long-term treatment of patients with acute exacerbation of chronic liver failure
      by albumin dialysis.

PMID- 10083609
TI  - Allogeneic immune responses augment rat cytomegalovirus replication in rats.

PMID- 10083610
TI  - Down regulation of in vivo and in vitro T cell responses post cytomegalovirus
      immune globulin intravenous (human) administration in sensitized renal transplant
      candidates.

PMID- 10083611
TI  - Long-term investigation of hepatitis G virus infection in renal transplant
      recipients with and without hepatitis B and C co-infection.

PMID- 10083612
TI  - Medial cell apoptosis precedes the development of intimal hyperplasia after
      transient allogeneic exposure in a rat aortic allograft model of chronic
      rejection.

PMID- 10083613
TI  - Quality of life and functional status of liver transplant recipients with
      recurrent viral hepatitis C.

PMID- 10083614
TI  - Subclinical pneumonitis during cytomegalovirus infection after kidney
      transplantation.

PMID- 10083615
TI  - No clinical evidence of hyperlipidemia as a risk factor for chronic renal
      allograft failure.

PMID- 10083616
TI  - Focal segmental glomerulosclerosis progression to end-stage renal disease within
      48 months is a risk factor for recurrence after pediatric renal transplantation.

PMID- 10083617
TI  - Immunosuppression is not required for reactivation of latent murine
      cytomegalovirus.
AB  - We have shown, for the first time, that TNF induces expression of MCMV IE RNA in
      the lungs of latently infected mice in the absence of immunosuppression. These
      initial data suggest that TNF may play an important role in the reactivation of
      latent MCMV, in the absence of immunosuppression, and provide a provocative
      insight into the mechanisms of CMV reactivation. Studies are in progress to
      determine whether genes associated with later stages of the viral life cycle are
      induced by TNF and whether infectious virus is produced.

PMID- 10083618
TI  - The role of Fas/FasL apoptotic pathway in the development of chronic rejection.

PMID- 10083619
TI  - Should recipient risk be a factor in choosing recipients for suboptimal donor
      hearts: a multi-institutional study.

PMID- 10083620
TI  - High-risk donors: expanding donor criteria.
AB  - Advances in the surgical techniques, preservation solutions, and methods for
      predicting eventual long-term renal function from expanded donors will be
      critical in allowing precise selection criteria for kidneys for transplantation,
      resulting in the optimum use of a scarce and precious resource. Until other
      options such as xenotransplantation or tissue engineering become realistic, the
      challenge for the millennium will be to identify which donor organs previously
      considered suboptimal can be safely used to expand the organ donor pool.

PMID- 10083621
TI  - Liver transplantation: quality of life related to prognosis.

PMID- 10083622
TI  - Immunity and tolerance are related, and governed by antigen migration and
      localization.

PMID- 10083623
TI  - Interleukin-1 beta induces endothelin-1 gene by multiple mechanisms.

PMID- 10083624
TI  - Idarubicin-anti-CD3 reduces vascular disease in mouse cardiac allografts.

PMID- 10083625
TI  - Management of renal colic with intranasal desmopressin spray.
AB  - This study evaluates the effectiveness of desmopressin renal spray, an
      antidiuretic drug, in treating patients with acute renal colic. One hundred and
      eight patients admitted to the emergency room of our hospitals with acute renal
      colic were included in the study. Each patient, except those with hypertension or
      other cardiac insufficiency, received 40 micrograms desmopressin intranasal
      spray. In 58 patients (53.7%) pain was eliminated 30 min after desmopressin
      administration. Forty-four patients (40.7%) did not respond to desmopressin and
      received prostaglandin synthesis inhibitors, while another 6 patients required
      intramuscular pethidine for pain relief. No patient showed any side effects. We
      conclude that the simplicity and effectiveness of intranasal desmopressin spray
      in treating renal colic makes this simple method a useful means of confronting a
      frequent and disturbing urological problem.

PMID- 10083626
TI  - [Antegrade scrotal embolization of varicocele: results].
AB  - The aim of this study is to judge the effectiveness of the new treatment of
      varicoceles, introduced in 1987 by Tauber: the antegradal scrotal sclerotherapy
      of varicoceles. From february 1996 to april 1998, we have realised 150 antegrade
      embolisations of varicoceles. The study is lead on 75 patients with mean time
      follow-up of 12 months. Patient's mean age is 20 years. 85% of patients had a
      grade 3 left varicocele and 15% a grade 2 left varicocele. The criterium of
      success rests on the lack of veinous flow-back during clinical examination, which
      is than confirmed by doppler-ultrasound. Clinical success is obtained in 87% of
      the cases and the doppler control is normal in 80% of the cases. We have 9% of
      minor complications, and no major complication. The number of failures in our
      study is higher than in Tauber' study, but is the same as those described in the
      other procedures of treatment of varicocele. On the other hand the surgical
      procedure is simple and the morbidity is low.

PMID- 10083627
TI  - [Results of artificial sphincter in a case of sphincter incontinence in the
      multiple surgery patient].
AB  - Stress incontinence represents 77 to 91% of female urinary incontinence, 10% of
      witch are sphincterial incontinence. The specific treatment of sphincterial
      incontinence is of periuretral injections or calls for an artificial sphincter.
      We present the retrospect of 12 patients having undergone several surgical
      treatments and having at last the benefit of an artificial sphincter since 1990.
      In majority, these patients had been operated for bladder neck hypermobility. The
      indication, preoperatory evaluations, surgical technics and results are
      discussed. During the mean follow-up of 40.5 months, 91.7% of patients are
      perfectly continent. The results are equal to those of other publications.

PMID- 10083628
TI  - [Ureteral reimplantation on psoas bladder: long-term results].
AB  - OBJECTIVE: To evaluate indications and long-term results of ureteral
      reimplantation with psoas hitch bladder. MATERIALS AND METHODS: Between January
      1985 and December 1997, we performed psoas-hitch ureteral reimplantation in 18
      patients (13 females and 5 males). Mean age was 48 years old. All ureteral
      injuries involved a pelvic portion of the ureter. The indication was: ureteral
      injury during gynecological procedures in 5 cases, stricture following open
      uretero-lithotomy in 3 cases, avulsion of the ureter during ureteroscopy in 1
      case, stricture following prior ureteral reimplantation in 3 cases, prostate
      cancer involving the distal ureter in 1 case, megaureter in 1 case, radiation
      therapy in 1 case, pelvic and ureteral endometriosis in 3 cases. Treatment
      consisted to adequate mobilization of the bladder, fixation of the posterolateral
      corner of the bladder to psoas and ureteral reimplantation with anti-reflux
      system. In all cases, psoas-hitch ureteral reimplantation has been performed
      because of an inability to perform end-to-end uretero-ureterostomy or direct
      uretero-neocystostomy. RESULTS: No complications were observed. At follow-up of 7
      months to 12 years (mean 5.7 years) we noticed 13 success (72.4%), 4 improvements
      (22.2%) and one patient (5.4%) was lost at follow-up. No nephrectomy was done.
      CONCLUSION: Psoas-hitch bladder ureteral reimplantation is simple, effective and
      a first-line procedure for the replacement of the long defects of the lower
      ureter.

PMID- 10083629
TI  - Endoscopic treatment of complete posterior urethral obliteration.
AB  - The management of posterior urethral obliteration remains a surgical challenge.
      We report our experience with 5 patients treated endoscopically for posterior
      urethral obliteration. We performed endoscopic reconstitution of the urethra
      followed by temporary self-dilation in five patients with complete short
      posterior urethral obliteration (less than 3 cm). Average follow-up is 31 months
      (21-53 months). During follow-up 4 of these patients required 1 or 2 internal
      urethrotomies within the first 4 to 24 months after treatment. But, any urethral
      stricture has not been established until the average 23.2 months (21 to 27
      months). The other fifth patient has no complication at twenty-first month
      postoperatively. One patient had impotence after the injury. Impotence continued
      and total incontinence developed after the endoscopic treatment. We believe that
      endoscopic treatment followed by temporary self-dilation could be a reasonable
      alternative to open urethroplasty in patients with an impassable short stricture.

PMID- 10083630
TI  - [Conservative treatment of stage III kidney injuries].
AB  - OBJECTIVE: The aim of this study is to evaluate the safety and effectiveness of
      conservative management in stage III renal trauma. MATERIAL AND METHODS: We
      reviewed the records of 150 patients who presented in our institution with renal
      trauma between 1986 and 1995. RESULTS: Minor injuries (stage I and II: 100 cases)
      were treated with expectant management. Only 3 patients required nephrectomy in
      this group. Stage III injuries were seen in 40 patients. The great majority (85%)
      were treated conservatively with renal sparing procedures such as endourologic
      techniques (14 cases), nephrorraphy or partial nephrectomy (20 cases). Total
      nephrectomy was performed in 15% of the cases and only for severely injured
      kidney or major associated intraabdominal injuries. In this group, none of the
      patients suffered from hypertension at follow-up. All patients (10 cases) with
      pedicle injury (stage IV) required total nephrectomy. CONCLUSION: Stage III renal
      trauma with urinary extravasation can safely be treated conservatively.

PMID- 10083631
TI  - Ductal ("endometrioid") adenocarcinoma of the prostate.
AB  - Ductal ("endometrioid") adenocarcinoma of the prostate is a rare variant of
      prostatic carcinoma which may have a different clinical presentation than the
      more common acinar adenocarcinoma. Ductal adenocarcinoma usually involves the
      urethra and the large periurethral prostatic ducts with direct spread through the
      more peripheral ductal system. Centrally located tumours have a much better
      prognosis than tumours involving the deep prostatic parenchyma. Local recurrence
      rate is high and five-year survival rate is as low as 24% for adenocarcinomas
      that have spread to the peripheral prostatic ducts. Although there have been some
      doubts about the role of hormonal therapy in ductal ("endometrioid")
      adenocarcinoma of the prostate, it is now agreed that therapeutic regimens should
      not be different from those offered to patients with conventional acinar
      adenocarcinoma.

PMID- 10083632
TI  - Unusual case of Munchausen's syndrome: factitious vesical lithiasis.
AB  - We report an uncommon case of a 38-year-old woman who admitted for bladder
      lithiasis undergoing repeated surgical management and being apparently recurrent.
      The intravenous pyelography and retrograde urethrocystography clear the urinary
      tract. Biologic evaluation eliminates any metabolic or endocrine cause. The
      confirmation of a factitious origin is given by fluorescence X analysis of the
      extracted stones which conclude to calcium carbonate structure and psychiatric
      care. The self-intromission of these calculi into the bladder is due to the
      personality disorder being in the frame of Munchausen's syndrome. Two years
      later, no recurrence is noted and an excellent psychiatric care is achieved.

PMID- 10083633
TI  - [An update of the pharmacological treatment of juvenile chronic arthritis].

PMID- 10083634
TI  - [The genetic factors associated with pediatric cancers].

PMID- 10083635
TI  - [The report of the Spanish Society of Pediatric Intensive Care: the distribution
      of pediatric intensive care in Spain].

PMID- 10083636
TI  - [An analysis of prior antibiotic treatment on the impact of meningococcal disease
      in children of the Valencian Community. The Study Group of Invasive Diseases].
AB  - OBJECTIVE: The objective of this study was to describe the effect of antibiotics
      given prior to hospitalization of children with meningococcal disease and to
      assess their relationship with disease outcome and microbiological isolation.
      PATIENTS AND METHODS: A prospective surveillance system in all hospitals of the
      Community of Valencia was implemented. All cases of children less than 15 years
      of age with clinically suspected invasive disease and: 1) N. meningitidis
      isolated in a normally sterile body fluid; 2) positive capsular antigens in blood
      or CSF and a positive Gram stain; and 3) clinical diagnosis of an invasive N.
      meningitidis disease. RESULTS: In a two-year period 157 cases were reported. In
      143 cases, data about antibiotic prescription prior to hospitalization was known.
      Of these, 24.5% had received antibiotics and none had received parenteral
      penicillin or cephalosporins. Oral antibiotics decreased bacterial isolation (p <
      0.001) and did not modify outcome (p = 0.66). CONCLUSIONS: Oral antibiotics, not
      recommended for N. meningitidis diseases, did not modify prognosis, but decreased
      bacterial isolation, and therefore worsened clinical handling of the cases and
      epidemiological studies.

PMID- 10083637
TI  - [An epidemiological analysis of bronchiolitis in the health region of Tarragona].
AB  - OBJECTIVE: The purpose of this study was to analyze the epidemiology of
      bronchiolitis in our area and to determine if changes in our medical
      installations have affected the course of this disease. PATIENTS AND METHODS:
      Infants less than 12 months of age with bronchiolitis that had been hospitalized
      between October, 1992 and January 1996 were studied retrospectively. The patients
      were divided into two groups; those attended in the old Pediatric Department and
      those seen in the new installations. RESULTS: In the first group, the majority of
      the thorax X-rays were normal and in the second air trapping was more frequently
      seen. The infants in the first group were admitted with a shorter evolution time
      and the mean hospitalization time was significantly higher (p < 0.05. IC = 95%:
      1.68-3.62) than in the second group (7.7 +/- 3.75 vs. 5 +/- 3.36 days,
      respectively). In addition, this difference was even more significant (p < 0.05.
      IC = 95%: 1.22-4.38) if syncytial respiratory virus had been isolated (8.93 +/-
      2.94 vs. 6 +/- 4.41 days, respectively). CONCLUSIONS: We did not find any
      epidemiological differences in our area in relationship to bronchiolitis during
      the past four years. We believe that the shorter hospitalization period in the
      second group could be attributed to working in the new facilities.

PMID- 10083638
TI  - [Lumbar puncture in a pediatric emergency department: something more than a
      diagnostic technic].
AB  - OBJECTIVE: The aim of this study was to know the incidence of serious bacterial
      infections (SBI) in children without sepsis or intracranial infection in which
      spinal puncture (LP) was performed in an Emergency Department. PATIENTS AND
      METHODS: A retrospective study of all 471 previously healthy children between 1
      month and 14 years of age in which a lumbar puncture was performed between July
      1995 and March 1997 in the Emergency Department of our hospital was performed.
      RESULTS: Two hundred and three children (43%) had sepsis, meningitis or
      encephalitis (aseptic meningitis 149, 31.6%; sepsis-bacterial meningitis 26,
      5.5%; nonspecific meningitis 26, 5.5%; encephalitis 2, 0.4%) and 14 (5.2%) had
      pneumonia. Of the other 254 children, 36 (14.1%) had a SBI: 19 urinary tract
      infections (E. coli), 11 bacteremia (Streptococcus pneumoniae 8, Salmonella
      enteritidis 1, Proteus mirabilis 1, E. coli 1, the latter two also having a
      positive urine culture) and 6 bacterial gastroenteritis (salmonella 5,
      Campylobacter jejuni 1). The incidence of SBI was significantly higher in the
      group of children younger than 5 years old (32/175, 18.2%) than in the older
      group (4/79, 5.0%, p = 0.009). Two patients died (one with pneumococcal
      meningitis and one with meningococcal sepsis). CONCLUSIONS: Children with fever
      and a normal result in the LP must be carefully examined and, especially in
      younger patients, urine, blood and stool (if stool abnormalities) cultures should
      be collected. These children must be closely observed in the hospital or at home
      and must be re-evaluated by their pediatrician in the following 24 hours.

PMID- 10083639
TI  - [Allogeneic bone marrow transplantation in children with severe acquired aplastic
      anemia. The long-term results. The Spanish Group for Bone Marrow Transplantation
      in Children (GETMON)].
AB  - OBJECTIVE: The objective of this study was to evaluate retrospectively the
      efficacy of allogeneic BMT in the treatment of childhood severe acquired aplastic
      anemia (SAAA). PATIENTS AND METHODS: Twenty-seven children aged 2 to 16 years
      (median 11 years) received a BMT from an HLA identical sibling. Conditioning
      consisted in irradiation (total, nodal or thoraco-abdominal) plus
      cyclophosphamide (120-200 mg/kg) in 15 patients and cyclophosphamide alone (200
      mg/kg) in the rest. Prophylaxis for graft-versus-host disease (GVHD) was
      cyclosporine and methotrexate in most patients. RESULTS: Twenty-four children
      achieved the bone marrow graft at a median of 18 days (neutrophils) and 21 days
      (platelets). Two patients failed engraftment and 1 had a late graft rejection.
      Three patients developed acute GVHD grades 3-4 and six chronic GVHD, which was
      extensive in 4 of them. Twenty patients/71%) are alive and disease-free at a
      median follow-up of 110 months and the estimated disease free survival at 6 years
      is 67%. CONCLUSIONS: Our results confirm that allogeneic bone marrow
      transplantation from an HLA identical sibling is the best treatment modality for
      children with SAAA. Acute GVHD associated with infections and graft rejection
      were responsible for treatment failures.

PMID- 10083640
TI  - [The evaluation of gonadal function in postpubertal patients treated for
      cryptorchism in childhood].
AB  - OBJECTIVE: Descent of the testes is essential for normal function, with
      cryptorchidism being associated with defective spermatogenesis. The postpubertal
      function of cryptorchid testicles seems to be related to the original location of
      the undescended testis and the age at the moment of treatment. The objective of
      this study was to evaluate the pubertal development and gonadal function in
      postpubertal patients treated for cryptorchidism during childhood. PATIENTS AND
      METHODS: Twenty postpubertal males with a mean age of 17.35 years (range: 15-21
      years) and treated for cryptorchidism during childhood were evaluated for
      pubertal development and gonadal function. A hormonal study which included basal
      determinations of testosterone, luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH), testicular volume assessed by Prader's orchidometer and semen
      analysis was performed on each patient. RESULTS: Complete virilization was
      observed in all patients. The start and development of puberty were normal in all
      cases (except one patient that started puberty at 10 years of age). Basal studies
      in all patients showed normal levels of LH and testosterone. FSH levels were
      increased in 3 patients and normal in the other 17 patients. Fourteen patients
      achieved normal spermatogenesis with more than 20 million spermatozoa/ml. In the
      other 7 patients (35%), 5 with unilateral cryptorchidism and 2 with bilateral
      cryptorchidism, the sperm count remained below 20 million with a range of 0.8 to
      18.4 x 10(6) spermatozoa/ml. The three males with elevated levels of FSH also
      presented oligospermia. CONCLUSIONS: The results obtained show that pubertal
      development is normal after cryptorchidism. Impaired spermatogenesis is a major
      factor in undescended testes. Basal SH levels can be useful in predicting
      germinal damage secondary to cryptorchidism.

PMID- 10083641
TI  - [Kawasaki disease. A report of 50 cases].
AB  - OBJECTIVE: We present 50 cases of Kawasaki's disease (KD), diagnosed and
      controlled in our hospital between January 1984 and December 1997. PATIENTS AND
      METHODS: Fifty patients were reviewed. In forty-six of these cases the onset was
      complete, according to the Research Committee of MLNS diagnosis criteria and four
      cases had incomplete onset. RESULTS: The ration male/female was 1.9/1. Both fever
      and oral cavity lesions were present in all cases. In 93.4% desquamation of
      fingers was observed. The most frequent skin lesion was maculopapular rash.
      Fourteen patients had atypical onset: adenophlegmon, aseptic meningitis,
      symptomatic hepatitis, parotiditis, queratopathia punctata and arthritis. Blood
      analysis showed alterations of high ESR (88% of cases), C-reactive protein (62%),
      leukocytosis (82%) and thrombocytosis (96%). Fifteen patients were treated with
      gamma globulin (IGIV), five received a single 2 g/Kg dose and ten received 400
      mg/Kg per day during four days. Eight percent of our cases produced
      cardiovascular complications, none that included coronary aneurysms. CONCLUSIONS:
      After IGIV treatment we observed a shortening of the febrile period and
      amelioration of clinical symptoms. No deaths were reported.

PMID- 10083642
TI  - [Moyamoya disease. A cause of vascular occlusion in childhood].
AB  - OBJECTIVE: The objective of this study was to review the cases of Moya-Moya
      diagnosed in our center. PATIENTS AND METHODS: We reviewed the Moya-Moya cases
      diagnosed from 1979 to 1997. We evaluated the following elements: age of clinical
      onset, sex, clinical features, complementary examinations, neuroimage, treatment
      and follow-up. RESULTS: Six patients were diagnosed. The first case appeared in
      1979 and the last in 1997. These included four boys and 2 girls, with ages
      between 5 months and 14 years. The initial clinical feature in all six cases was
      acute hemiparesis, noting that in one case this was preceded by homolateral
      seizures. Neuroimaging revealed ischaemic infarction areas in brain CT or MNR.
      The diagnosis was based on angiography, where in four cases there appeared
      bilateral occlusion of the internal carotid, or of the anterior or middle
      cerebral arteries and in the other two there was a unilateral occlusion of the
      interior carotid and middle cerebral arteries. Regarding etiology, in four
      patients the dysfunction was due to either fibromuscular dysplasia of the
      carotid, neurofibromatosis, cranial trauma or to Down's syndrome. In the other
      two cases no other primary cause was found. CONCLUSIONS: Acute stroke is an
      infrequent disease of pediatric age patients, however it is necessary to do a
      thorough angiography study to rule out the Moya-Moya like vascular anomalies.

PMID- 10083643
TI  - [Perinatal antecedents, psychomotor retardation, learning difficulties and family
      history. Are they a risk factor for epilepsy?].
AB  - OBJECTIVE: Epilepsy has been associated with certain circumstances such as
      perinatal pathology, learning difficulties, head trauma, infections of the
      central nervous system, febrile seizures and family history of epilepsy. The
      objective of our study was to analyze the association of the mentioned
      circumstances with epilepsy in a group of children with generalized spike-wave (S
      W) in the electroencephalogram (EEG). PATIENTS AND METHODS: One hundred seventy
      pediatric patients with, S-W were found from a register of 39,322 consecutive
      EEGs. The patients were classified into 2 groups: epileptic and non-epileptic.
      Both groups were compared for the presence of known risk factors of epilepsy.
      RESULTS: Of the 170 patients, 154 (90.6%) were epileptic and 16 (9.4%) were not.
      Mean follow-up was 4.5 years. Neither past medical antecedents nor family history
      was found to be associated with epilepsy. CONCLUSIONS: The risk of epilepsy in
      children with S-W in the EEG is not associated with problems in pregnancy, the
      birth or neonatal period, learning difficulties or family history of epilepsy.

PMID- 10083644
TI  - [The effects of arterial hypertension during pregnancy on birth weight,
      intrauterine growth retardation and neonatal evolution. A matched case-control
      study].
AB  - OBJECTIVE: To determine the impact of hypertensive disorders in pregnancy on
      birth weight, small-for-gestational age births (SGA) and neonatal outcome.
      DESIGN: Matched case-control study. SETTING: A Tertiary Neonatal Intensive Care
      Unit. POPULATION AND METHODS: The effects of maternal hypertension were analyzed
      in 11,358 infants born between January 1990 and December 1996 at the Italian
      Hospital of Buenos Aires. Infants born to mothers with pregnancy-induced
      hypertension, preeclampsia or eclampsia were included. Each infant was matched
      for gestational age to 1 control infant born to normotensive mothers. Exclusion
      criteria were: twins, intrauterine infections, chronic hypertension and major
      malformations. MAIN OUTCOME MEASURES: Birth weight, incidence of SGA infants,
      neonatal outcome. RESULTS: 279 infants of hypertensive mothers and 279 controls
      met the inclusion/exclusion criteria and were enrolled. Maternal hypertension was
      significantly associated with a higher rate of C-section (OR = 3.80; 95% CI: 2.64
      5.50); SGA infants (OR = 7.08; 95% CI: 3.07-18.6), low birth weight (LBW) (OR =
      1.8, 95% CI: 1.24-2.60) and very low birth weight infants (VLBW) (OR = 2.14; 95%
      CI: 1.13-4.19). The frequency of low Apgar score at 5 minutes (OR = 3.63; 95% CI:
      1.12-15.3), necrotizing enterocolitis (OR = 3.33; 95% CI: 1.23-10.30) and
      polycythemia (OR = 3.63; 95% CI: 1.12-15.3) was significantly increased in
      infants born to hypertensive mothers. There were no significant differences
      regarding other causes of neonatal morbidity and mortality rate. CONCLUSIONS:
      Hypertension in pregnancy mainly increased the risk of SGA infants. Furthermore,
      infants of hypertensive mothers had a higher incidence of LBW, VLBW, low Apgar
      score at 5 minutes, necrotizing enterocolitis and polycythemia.

PMID- 10083645
TI  - [The Townes-Brocks syndrome in Spain: the epidemiological aspects in a
      consecutive series of cases].
AB  - INTRODUCTION: Townes-Brocks syndrome is constituted by a multi-systemic pattern
      of congenital anomalies with autosomal dominant inheritance. The most
      characteristic defects are those affecting hearing and the auricle, anal atresia
      and thumb anomalies. PATIENTS AND METHODS: We present the epidemiological
      characteristics of six cases of Townes-Brocks syndrome identified in the
      consecutive series of 25,967 malformed live born infants detected among 1,431,368
      live births surveyed by the ECEMC (Spanish Collaborative Study of Congenital
      Malformations) between April 1976 and June 1997. RESULTS AND CONCLUSIONS: The
      minimal estimated frequency of Townes-Brocks syndrome in our data is 0.42 cases
      per 100,000 liveborn infants. These infants have low birth weights. Similar to
      other published studies, we have observed in our cases a wide variation in the
      clinical expression of the syndrome, showing great inter-family, as well as
      intrafamily variability.

PMID- 10083646
TI  - [Cardiac tumors. Our experience with 4 cases].

PMID- 10083647
TI  - [Moyamoya disease. A case report and review of the literature].

PMID- 10083648
TI  - [Recurrent neonatal sepsis due to Streptococcus B].

PMID- 10083649
TI  - [Type-III hyperlipoproteinemia in a girl with Wilson's disease].

PMID- 10083650
TI  - [The Ellis-van Creveld syndrome (chondroectodermal dysplasia). Apropos a clinical
      case].

PMID- 10083651
TI  - [Sepsis due to azole-resistant Candida albicans in a high-risk premature infant].

PMID- 10083652
TI  - [Edemas and proteinuria in a patient with cystic fibrosis].

PMID- 10083653
TI  - [Epidemiology and scientific methodology applied to pediatrics (III): an
      introduction ot statistical analysis in epidemiology].

PMID- 10083654
TI  - [Advances in pediatric emergency medicine].

PMID- 10083655
TI  - [Vaccination against hepatitis B and multiple sclerosis].

PMID- 10083656
TI  - [Tuberculous infection in children: some details].

PMID- 10083658
TI  - [Comments on the article: "Ophthalmoplegia-ataxia-areflexia in pediatrics. 3 new
      cases and a review of the literature"].

PMID- 10083659
TI  - [A seroepidemiologic study of human parvovirus B19 infection in children].

PMID- 10083660
TI  - [Cutis marmorata telangiectatica congenita: a reminder of the review].

PMID- 10083661
TI  - [Comments on the evaluation of an instantaneous infrared ear thermometer].

PMID- 10083662
TI  - [The sequential use of antipyretics. Based on evidence or on habit?].

PMID- 10083663
TI  - [Management of colorectal cancer in Australian hospitals. Twenty four years'
      experience].
AB  - This study analyses time trends in clinical features tumour pathology and
      treatment outcomes of patients with colorectal cancer (CRC) treated by surgery
      alone during the period 1971 to 1994 in a large Australian tertiary referral
      centre. Throughout this period, both surgical technique and pathology reporting
      were standardized and a specialized unit of colon and rectal surgery was
      established in 1980. Improvement in overall survival during this 24 year period
      reflects changes in tumour stage with an increasing proportion of stage A
      tumours, declining proportions of stage D tumours, and some improvement in
      survival for stages B and C colon cancer only.

PMID- 10083664
TI  - [Laparoscopic treatment of perforated peptic ulcer].
AB  - STUDY OBJECTIVE: Contribution to evaluation of the place of laparoscopic surgery
      in the treatment of perforated peptic ulcer. PATIENTS AND METHODS: Between
      January 1992 and November 1997. 17 consecutive patients underwent laparoscopic
      suture of a perforated peptic ulcer, with or without omentoplasty. RESULTS:
      Treatment was performed entirely by laparoscopy in 13 cases (76%). The median
      operating time was 105 min (50-220 min). The median number of doses of analgesia
      administered to each patient was 8 (3-20 doses). The medium hospital stay was 6
      days (2-23 days). Two patients (12%) died. In 11 cases, gastroscopy was performed
      between 1 and 4 months after the operation, revealing healing of the ulcer in 10
      cases and persistence of the ulcer in one case. None of the patients were
      readmitted to hospital for ulcer complications, with a median follow-up of 35
      months (1-63 months). CONCLUSION: The laparoscopic treatment of perforated
      duodenal is a technically simple and effective procedure, intermediate between
      conventional surgical treatment and Taylor's method. Laparoscopic surgery may
      therefore have a real place in the treatment of perforated peptic ulcer.

PMID- 10083665
TI  - [Respiratory morbidity and mortality following transhiatal esophagectomy in
      patients with severe chronic obstructive pulmonary disease].
AB  - In order to assess the influence of severe chronic obstructive pulmonary disease
      on the pulmonary morbidity and mortality following transhiatal oesophagectomy,
      the authors reviewed 136 consecutive patients who underwent oesophageal cancer
      resection by a transhiatal approach. Nineteen patients had a forced expiratory
      volume in one second (FEV) lower than 60% of the theoretical value, indicating
      severe chronic obstructive pulmonary disease. The other group of 117 patients had
      a FEV higher than 60% of the theoretical value. Pulmonary complications occurred
      in 36 patients: 23 (64%) were minor and 13 (36%) were major. Severe chronic
      obstructive pulmonary disease did not significantly increase pulmonary morbidity.
      However, pulmonary complications occurring in this group of patients appeared
      more severe with a significant increase in major pulmonary complications (21%
      versus 8%, p = 0.05) and respiratory mortality rates (10% versus 1.6%, p = 0.04).
      One factor was significantly correlated to respiratory mortality: age higher than
      75 years (p = 0.006). Severe chronic obstructive pulmonary disease does not
      constitute a contraindication for transhiatal oesophagectomy. However, this
      approach should be reserved for patients under 75 years of age, in order to
      obtain respiratory morbidity and mortality rates comparable to those of patients
      with normal spirometry.

PMID- 10083666
TI  - [Laparoscopic treatment of recurrent inguinal hernia after only mesh].
AB  - The recurrences of inguinal hernia after onlay mesh may cause technical
      difficulties for a new repair. The aim of our study was to assess intraoperative
      findings, feasibility and results of laparoscopic transpreperitoneal mesh onlay
      in this indication. Twenty-one repairs were performed. In all cases, direct,
      internal, inguinal recurrences were observed, associated in two cases with an
      external or femoral recurrence. In 16 cases, there were no adhesions in the
      peritoneal cavity. The were no conversions and peritonealisation was always
      completed. The mean length of hospitalization was 2.7 days. Our study suggests
      that technical errors during the first procedure, insufficient mesh or wrongly
      positioned are responsible for recurrence and allow reinsertion of a mesh
      laparoscopy via transpreperitoneal in this indication.

PMID- 10083667
TI  - [Long-term results of 186 patients with large incisional abdominal wall hernia
      treated by intraperitoneal mesh].
AB  - Massive incisional abdominal wall hernias are frequent and difficult to repair,
      especially when they are large, multiply recurrent and when associated high with
      risk factors. We report the long-term results of 192 hernia repairs (in 186
      patients) by non-resorbable mesh placed intraperitoneally and fixed by fascia
      stapler. We describe the details of the technique. There were no deaths. Early
      and late wound infections occurred in 11.7%, late occlusions in 6.3% and
      recurrence in 16%. Four percent of patients required removal of the mesh. The
      main caracteristic of this study was the long follow-up period (mean duration =
      77 months). In view of the good results (70%), simplicity and quite execution of
      this technique, intraperitoneal mesh placement should be considered in the repair
      of large hernias when a prothesis is required.

PMID- 10083668
TI  - [Current indications and results of pulmonary decortication for nontuberculous
      chronic empyema].
AB  - Pulmonary decortication for nontuberculous chronic empyema has become a rare
      operation, whose indications and results are now rarely analysed and discussed.
      The authors report a series of 40 consecutive decortications performed over a
      period of 15 years. PATIENTS: 40 patients treated by pulmonary decortication over
      15 years for nontuberculous chronic empyema secondary to pneumonia (27 cases; 2/3
      of cases), post-traumatic haemothorax (5 cases), iatrogenic infection after
      pleural tap (5 cases) and septicaemia (3 cases). Chronic empyema had been present
      for an average of 6 months (1 to 60 months). Decortication was performed for
      drainage of persistent pleural suppuration in 22 cases and to release the
      encysted lung in 18 cases. Decortication, always comprising parietal pleural
      stripping and visceral decortication, lasted an average of 3 hours (2 to 8
      hours), and was accompanied by mean bleeding of 1 litre (of 200 ml to 3.41).
      RESULTS: 27 patients (67%) had an uneventful postoperative course, with drainage
      for 6 days and a mean hospital stay of 13 days. 13 patients (33%) developed
      various complications, mainly re-expansion defects (10 cases), responsible for
      pyothorax in 4 cases, 3 of which required secondary drainage. One patient died
      from intestinal obstruction in a context of peritoneal carcinomatosis (operative
      mortality: 2.5%). 25 patients were reviewed with a mean follow-up of 54 months,
      with complete pulmonary re-expansion in 23 cases (92%) and a residual pouch in 2
      cases. Vital capacity (VC) was evaluated in 8 patients, with a mean improvement
      of 40% (15 to 66%) in 6 patients, stable VC in one patient, and a 25% reduction
      in the last patient, a smoker and with chronic bronchitis. CONCLUSION: Pulmonary
      decortication is an effective, but relatively major operation to treat chronic
      encysted empyema. Encystment must be prevented by effective drainage of empyema,
      now facilitated by the possibility of early videothoracoscopic pleural
      debridement.

PMID- 10083669
TI  - [Electrical injuries during laparoscopy].
AB  - Electrical injury is uncommon during surgical laparoscopy, but may be serious.
      Following a comprehensive literature review, we describe five mechanisms of burn
      injuries: direct contact, electric arc, insulation failure, direct or capacitive
      coupling. We discuss these mechanisms and suggest simple preventive measures
      designed to ensure optimal safety.

PMID- 10083670
TI  - [What is the contribution of biochemistry?].

PMID- 10083671
TI  - [What is the contribution of imaging?].
AB  - Thyroid imaging has an essentially diagnostic value, but is also plays a role in
      definition of indications and operative techniques. Ultrasound is the most useful
      examination. Scintigraphy has become less useful, but remains indicated in
      hyperthyroidism and in certain retrosternal goitres inaccessible to ultrasound.
      The other examinations only have a limited value.

PMID- 10083672
TI  - [What is the contribution of aspiration cytology?].
AB  - Aspiration cytology of thyroid nodules is essentially designed to determine the
      benign nature of the nodule in order to avoid purely diagnosis surgery. It is
      reliable in the diagnosis of anaplastic papillary and medullary carcinomas and
      most lymphomas, but is more problematical for the diagnosis of the benign or
      malignant nature of Hurthle cell tumours and certain vesicular tumours, in which
      cytology reveals a suspicious, doubtful or undetermined appearance. However,
      whether they are unambiguous or doubtful, fine needle aspiration cytology results
      help the surgeon to define the therapeutic strategy under the best possible
      conditions. A therapeutic approach is proposed, based on the formulation of
      aspiration cytology results into benign, malignant, suspicious and inadequate.

PMID- 10083673
TI  - [Examination of the vocal cords before thyroidectomy].

PMID- 10083674
TI  - [What examinations should be required in a patient with a thyroid nodule?].

PMID- 10083675
TI  - [What examinations should be performed in the case of retrosternal or compressive
      goiter?].

PMID- 10083676
TI  - [Place of complementary investigations before thyroidectomy. What examinations
      should be required before reoperation?].

PMID- 10083677
TI  - [Brief history of the hospital bed].
AB  - Start as simple litter for several patients in the Middle-Age, the hospital's bed
      had progressively change to the first mechanical beds in the XIX century.

PMID- 10083678
TI  - [Emergency pancreatoduodenectomy without primary anastomosis. Salvage surgery?].

PMID- 10083679
TI  - [Three cases of diverticular perforation of the caecum and ascending colon].
AB  - Perforation of the ascending colon secondary to diverticulitis is an uncommon
      surgical emergency. It is usually diagnosed during exploratory laparotomy for
      suspected appendicitis. We report three cases of cecal perforation due to
      diverticulitis. Imaging work-up, especially computed tomography can establish the
      preoperative diagnosis of cecal diverticulitis and guide its management.

PMID- 10083680
TI  - [Ehlers-Danlos syndrome and spontaneous colonic performation: report of one
      case].

PMID- 10083682
TI  - 'The virtuous cycle': implications of the health and medical research strategic
      review.

PMID- 10083683
TI  - Barriers to immunisation in general practice.
AB  - OBJECTIVE: To identify barriers to immunisation in general practice. METHOD: The
      study was conducted in Perth, Western Australia, as a cross-sectional postal
      survey between November 1996 and January 1997. Questionnaires were sent to all
      known GPs in three of the seven metropolitan Divisions of General Practice, of
      whom 301 (72%) responded. RESULTS: When a child presented with a minor illness
      and there were no contraindications to immunisation, 62% of GPs said they would
      always or frequently offer immunisation. Immunisation would be withheld
      incorrectly because of an upper respiratory tract infection by 43% of GPs and
      because of antibiotics by 50%. Combined diphtheria-tetanus vaccine (CDT) would be
      substituted incorrectly for diphtheria-tetanus-pertussis vaccine (DTP) by 41% if
      there was an unexplained temperature of 38 degrees C following a previous dose of
      DTP. While more than half (56%) reported that vaccines were correctly stored,
      only 26% reported that the refrigerator temperature was checked daily. Eighty per
      cent reported that they completed an Australian Childhood Immunisation Register
      notification form. CONCLUSIONS: GPs require ongoing education about contra
      indications to immunisation and when substitution of CDT for DTP is required.
      There is room for increased opportunistic immunisation and encouragement to
      notify the Australian Childhood Immunisation Register when they immunise a child.
      IMPLICATIONS: A major challenge is to find an innovative approach that would
      encourage and enable GPs to assess immunisation status and offer immunisation
      where appropriate at every clinical encounter.

PMID- 10083684
TI  - Projecting coronary heart disease incidence and cost in Australia: results from
      the incidence module of the Cardiovascular Disease Policy Model.
AB  - OBJECTIVE: To project the incidence rates of coronary heart disease and the
      number of hospitalised incident coronary heart disease cases and hospital costs
      associated with the first hospital admission, for males and females aged 45-69,
      up to 2014 in Australia. METHOD: A computer simulation model using a
      microsimulation technique was developed to simulate individuals' coronary heart
      disease history over time for a sampled Australian population characterised by
      major coronary risk factors. Using the simulated incidence rates, population and
      hospital cost data, the number of hospitalised incident coronary heart disease
      events and hospital costs associated with the first hospital admission were
      projected. RESULTS AND CONCLUSIONS: If current cohort-specific coronary risk
      factor distributions change only by a location shift and the availability and
      efficacy of current treatment patterns prevail, the model projects declines of
      13% and 24% in incidence rates for males and females aged 45-69 respectively by
      2014. However, because the population aged 45-69 is projected to increase over
      the same period, the number of projected hospitalised coronary heart disease
      events and the hospital costs associated with the first admission will increase
      by more than 40%. IMPLICATIONS: A modeling strategy which integrates information
      on coronary risk factor distributions, epidemiologic, demographic and economic
      data can provide comprehensive projections that assist future health care
      planning in the area of coronary heart disease.

PMID- 10083685
TI  - Socio-economic, migrant and geographic differentials in coronary heart disease
      occurrence in New South Wales.
AB  - OBJECTIVE: This study examines the variation in coronary heart disease (CHD)
      mortality and acute myocardial infarction (AMI) by socio-economic status (SES),
      country of birth (COB) and geography (urban/rural) in the total population of New
      South Wales (Australia) in 1991-95. METHOD: CHD deaths and AMI are from complete
      enumerations of deaths and hospital admissions, respectively; and population
      denominators are from census information. Data are examined separately by sex,
      and comparisons of SES groups (based on municipalities), COB and region are
      analysed using Poisson regression, after adjustment for age. RESULTS: The study
      identified higher risk for AMI admissions and CHD mortality in lower SES
      populations with significant linear trends, for both sexes, adjusted for age,
      region and COB. According to the population attributable fractions (PAF), 23-41%
      of the risk of CHD occurrence is due to SES lower than the highest quartile. The
      higher age-adjusted risk for CHD occurrence in rural and remote populations for
      both sexes, compared with urban communities, was lessened by adjustment for COB,
      and all but abolished when also adjusted for SES.COB analysis indicated
      significantly lower age-adjusted AMI admissions and CHD mortality compared with
      the Australian-born. CONCLUSIONS: Higher risks for CHD in rural populations
      compared with the capital city (Sydney) are due, in part, to lower SES, lesser
      migrant composition. IMPLICATIONS: Strategies for reducing CHD differentials
      should consider demographic factors and the fundamental need to reduce socio
      economic inequalities, as well as targeting appropriate prevention measures.

PMID- 10083686
TI  - The New Zealand Socioeconomic Index: developing and validating an occupationally
      derived indicator of socio-economic status.
AB  - OBJECTIVE: Following revision of the international standard classification
      (ISCO88), to update and validate on health data an occupationally derived
      indicator of socio-economic status (SES) adapted to changing occupational and
      demographic conditions. METHOD: The development of the New Zealand Socioeconomic
      Index (NZSEI) is based on a 'returns to human capital' model of the
      stratification process and uses data from the 1991 New Zealand Census (n = 1,051,
      926) to generate scores for 97 occupational groups. The construct validation of
      the scale is carried out on data from the 1992-93 nationwide Household Health
      Survey (n = 3,000) using three health indicators (self-assessed health, cigarette
      smoking, general practitioner visits). RESULTS: In general, the results are
      consistent with expected socio-economic patterns drawn from the literature for
      the three indicators. CONCLUSIONS: While further work is required on a number of
      methodological and conceptual issues, the NZSEI provides a robust, standardised
      and internationally comparable occupational scale of SES for both males and
      females in either full- or part-time employment. IMPLICATIONS: The NZSEI can be
      used on routinely collected occupational data. It has a clear conceptual
      rationale, updates existing SES scales, and provides a link to international
      standards in SES and occupational classification.

PMID- 10083687
TI  - Water fluoridation, bone mass and fracture: a quantitative overview of the
      literature.
AB  - OBJECTIVE: To use the technique of meta-analysis to address the following
      research questions: Is water fluoridation associated with altered fracture risk
      at a population level and are the differences between studies consistent with
      confounding or chance variation between studies? METHOD: The data sources
      utilised were Medline 1966-97, reviews and bibliographies. The search terms were
      fluoridation, bone mass and/or fracture. We included all observational studies
      published in English relating water fluoridation to bone mass and/or fracture in
      the initial assessment. RESULTS: Water fluoridation had no evident effect on
      fracture risk (RR 1.02, 95% CI 0.96-1.09, n = 18 studies). There was marked
      heterogeneity between studies which could be explained, in part, by the
      combination of gender, urbanicity and study quality (R2 0.25, p = 0.05, weighted
      analysis). CONCLUSIONS: Water fluoridation both at levels aimed at preventing
      dental caries and, possibly, at higher naturally occurring levels appears to have
      little effect on fracture risk, either protective or deleterious, at a population
      level. The small effect on bone mass seen in studies performed at the individual
      level is consistent with this finding. Variation between studies is also likely
      to be due to differences in the distribution of other recognised fracture risk
      factors between different populations. Confirmation of these findings is required
      in large studies performed at the individual level.

PMID- 10083688
TI  - Falls among healthy, community-dwelling, older women: a prospective study of
      frequency, circumstances, consequences and prediction accuracy.
AB  - OBJECTIVE: Most studies of falls among older people have focused on those with
      some degree of balance or mobility impairment. This study aimed to establish
      whether falls and associated injuries were a major problem among healthy, older
      women, whether there were some common features in the falls, and whether these
      falls could be accurately predicted. METHOD: Ninety-six healthy, active community
      dwelling women in Melbourne, Australia, aged at least 70 years (mean 74.1 +/-
      4.0) were initially measured on a comprehensive series of laboratory and clinical
      balance tests, gait, strength and psychometric measures. Subjects were monitored
      for falls events, circumstances and consequences by use of falls diaries and
      monthly phone calls. Baseline measures of clinical balance measures and gait were
      comparable to other studies reporting scores on these measures in samples of
      healthy older people. RESULTS: During the 12-month follow-up period, 49% of
      subjects fell, with 23% falling more than once; 9% suffered fractures as a result
      of their fall and 10% suffered strains or other moderate injuries. Many of the
      falls occurred during non-threatening activities such as walking, often under
      altered sensory or environmental conditions. Multivariate logistic regression
      identified gait symmetry and gait double support duration as the variables most
      strongly associated with prediction of multiple fallers. CONCLUSIONS: The results
      highlight that falls are a major problem among healthy active older women, and
      that targeted falls prevention programs are required for this group.

PMID- 10083689
TI  - The extent and nature of televised food advertising to New Zealand children and
      adolescents.
AB  - OBJECTIVE: There has been international concern over the balance of television
      advertising for healthy and less-healthy foods to which children and adolescents
      are exposed. This study examined the extent to which 9-17 year old New Zealanders
      were exposed to advertising for different food groups over a year and compared
      New Zealand rates of advertising with a 13-country study. METHOD: 'People meter'
      data collected over three months--May and September 1995 and February 1996--and
      food advertising from a sample week of television during hours when children were
      likely to be watching were also examined. Comparison was made with a similar 1989
      South Australian study and an international study covering 13 countries. RESULTS:
      Both the exposure estimated for a year and the opportunities for exposure during
      the sample week were highest for sweet snacks, drinks, fast food/takeaways and
      breakfast cereals. There were very low levels for fruit, vegetables, and
      meat/fish/eggs. Water was not advertised in any sample month. Comparisons with
      the 13-country study showed New Zealand had the third-highest rate of food
      advertising, the highest rate of confectionery and drinks advertising, and the
      second-highest rate of restaurant advertising which included fast food
      restaurants. CONCLUSION: Current patterns of food advertising pose a conflict of
      interest between public health and commercial interests. Regulation of food
      advertising may be needed to address this in order to improve future health.

PMID- 10083690
TI  - Obtaining resources for evidence-based public health initiatives at the local
      level: insights from the Central Sydney Tobacco Control Plan.
AB  - OBJECTIVE: In response to inquiries regarding the processes of developing a
      Tobacco Control Plan (TCP) for the Central Sydney Area Health Service (which in
      1997 allocated dedicated funding of $ 800,000 over 2 1/2 years to implement the
      plan), this article describes the strengths and weaknesses of the TCP and
      outlines the process which contributed to its funding. CONCLUSIONS: Consistent
      with national and state priorities, the TCP recommended strategies based on best
      available evidence in the four action areas: reducing sales of cigarettes to
      minors, marketing, passive smoking and smoking cessation. Funding of this amount
      for a single public health issue at a local level represents a unique achievement
      in the application of an evidence-based approach to population health.
      IMPLICATIONS: Key elements of our advocacy methods included the involvement of
      all key primary health care and clinical stakeholders; comprehensive background
      research to identify evidence-based strategies; careful attention to budget
      options; strategic lobbying of senior staff and decision makers; the proposal for
      a multidisciplinary management structure for the TCP and specifications for
      funding allocation and evaluation. Early achievements and other reflections are
      discussed.

PMID- 10083691
TI  - Differences in management of heart attack patients between metropolitan and
      regional hospitals in the Hunter Region of Australia.
AB  - OBJECTIVES: To test the hypothesis that among patients with acute myocardial
      infarction (AMI) length of hospital stay, drug use in hospital and on discharge
      were different between metropolitan and regional hospitals after adjusting for
      differences in patient baseline risk. METHODS: A retrospective cohort study using
      a community-based register of heart attack patients assessed 1,406 patients
      admitted for definite AMI to three metropolitan and five regional hospitals in
      the Lower Hunter Region of NSW, between January 1, 1990, and March 31, 1994.
      RESULTS: Patients in metropolitan hospitals were significantly less likely to
      stay in hospital for more than seven days (adjusted odds ratio = 0.50; 95% CI
      0.34-0.73), significantly more likely to receive ACE inhibitors (adj. OR = 1.47;
      1.27-1.71) and less likely to receive calcium channel blocker (adj. OR = 0.70;
      0.54-0.98). Regardless of disease severity, metropolitan hospitals had a higher
      percentage of patients for whom drugs shown to decrease mortality after AMI were
      used (streptokinase, aspirin, ACE inhibitor); a lower percentage of patients
      received drugs shown to have no benefit or even a detrimental effect (calcium
      channel blocker). Both groups had relatively low use of beta blocker, also shown
      to be of benefit. CONCLUSIONS: Regional hospitals had longer hospital stays than
      metropolitan hospitals and less use of drugs of proven benefit.

PMID- 10083692
TI  - Alcohol portrayal in Australian prime time television in 1990 and 1997.
AB  - OBJECTIVE: This study examines the frequency of scenes involving alcoholic and
      non-alcoholic drinking acts in Australian TV serials in 1990 and 1997. METHOD: In
      1990 and 1997, 87.5 and 85 hours (respectively) of prime time Australian serials
      were video taped. Tapes were coded using a standard protocol, including visual or
      verbal references to alcoholic beverages and the act of consuming or preparing to
      consume any type of beverage. RESULTS: In 1990 and 1997, prime time viewers saw
      on average 2.6 acts of alcohol consumption per hour. There was a statistically
      significant threefold decrease in the total number of references to alcohol on
      prime time Australian serials (primarily accounted for by a significant reduction
      in the incidental depiction of alcohol), an almost halving of the number of
      episodes that made some reference to alcohol and less consumption of beverages
      (both alcoholic and non-alcoholic) in 1997 compared with 1990. CONCLUSIONS: The
      decrease in incidental references to alcohol was not due to an obviously more
      socially responsible depiction of alcohol. In both 1990 and 1997, uncritical
      viewers could conclude from watching Australian TV serials that alcohol is
      everywhere, is there to be drunk, is used and accepted by all ages and both sexes
      and is rarely associated with any negative consequences. IMPLICATIONS: The
      portrayal of health or risk-taking behaviour on television may influence the
      perception of viewers that certain behaviours are 'normal', common or acceptable,
      may encourage modelling of that behaviour and may indirectly influence the policy
      agenda.

PMID- 10083693
TI  - Vietnamese women and Pap smears: issues in promotion.
AB  - OBJECTIVE: Australian data indicate that Vietnamese-born women in Australia have
      a significantly higher incidence of cervical cancer than other Australian women.
      This study explored self-reported factors associated with Vietnamese-born women's
      participation in cervical screening. METHOD: A structured 60-item questionnaire
      was used to conduct an interview survey with 199 Vietnamese-born women over the
      age of 18 years and resident in Adelaide. RESULTS: Eighty-seven per cent (87%) of
      the women had heard of a Pap smear and 75% had had a test at some time. Reported
      participation increased with age, education level, marriage and length of stay in
      Australia. The family doctor was the most important source of information about
      Pap smears and the majority of the women reported they would have a smear if
      recommended by their doctor. Friends and family were the second information
      source about cervix screening. CONCLUSIONS AND IMPLICATIONS: These findings have
      clear implications for practice. Strategies to promote preventive health messages
      to this group of women should involve general practitioners and peer networks.

PMID- 10083694
TI  - The 'easy street' myth: self harm among aboriginal and non-aboriginal female sole
      parents in urban state housing.
AB  - OBJECTIVE: To test the hypothesis that, controlling for socio-demographic
      factors, destructive behaviour among Aboriginal and non-Aboriginal female sole
      parents will not be significantly different. METHOD: This study took place among
      an urban population of sole parents in Adelaide, South Australia, living in
      government housing. Two sample subsets were made up of 52 Aboriginal and 45 non
      Aboriginal mothers from similar postcodes. Trained interviewers administered a
      questionnaire which, in addition to basic demographic data, elicited information
      concerning finance, housing, upbringing, experience of abuse and police
      interaction. The major issue of concern in the study was suicide attempt.
      RESULTS: 1-in-3 of the whole sample, 2-in-5 of the non-Aboriginal and 1-in-4 of
      the Aboriginal subset had attempted suicide at least once and half more than
      once. Statistical differences among 'attempters' vs. 'non-attempters',
      irrespective of ethnicity, included increased familial alcohol abuse, physical
      and sexual abuse, economic difficulty, poor self esteem and perceived
      discriminatory treatment by welfare agencies and, in the case of Aboriginals, by
      police. CONCLUSION: The social environment is critical to understanding
      destructive behaviour, including self-harm, regardless of culture or ethnicity.
      The data show that suicide attempts among female sole parents in State-housing is
      one of the few health indices for which Aboriginal statistics are less than for
      non-Aboriginals. IMPLICATIONS: It is evident that class, rather than ethnicity,
      better explains self-harm in this urban population. It is suggested that
      reluctance to access services, especially in times of crisis, relates in part to
      perceptions of care services and that, for Aboriginals, the value of culturally
      appropriate community-run services have specific public health and policy
      implications.

PMID- 10083695
TI  - Evaluating Tackling Rugby Injury: the pilot phase for monitoring injury.
AB  - OBJECTIVE: To assess the suitability of two previously unused data sources for
      monitoring rugby injury throughout New Zealand. METHOD: Interviews were conducted
      with respondents sampled from players registered with the Rugby Football Unions
      (RFUs) and players claiming for rugby injuries from the Accident Rehabilitation
      and Compensation Insurance Corporation (ACC) in Auckland and Dunedin. RESULTS: Of
      the 500 RFU players sampled, 63% were interviewed and of these 39 (12%) had been
      injured playing rugby union. Of the 456 ACC claimants sampled, 66% were
      interviewed and 265 (88%) had been injured playing rugby union. CONCLUSION:
      Identifying injured players through ACC claims was more efficient, both
      procedurally and because a smaller sample size was required to detect changes in
      incidence. IMPLICATIONS: With no routine surveillance of sports injury being
      undertaken, recording sporting codes in national injury surveillance systems
      would assist the monitoring of sports injury.

PMID- 10083696
TI  - Barriers to Pacific women's use of cervical screening services.
AB  - OBJECTIVE: The present study explored barriers to the use of cervical screening
      information and services from the perspective of Pacific women. METHOD:
      Qualitative, face-to-face interviews based on a snowball sampling approach were
      used in Palmerston North, New Zealand, in 1997, to assess attitudes among 20
      Pacific women. RESULTS: The study found a high level of awareness of a local
      cervical screening program. Specific barriers determined were: a resistance to
      being defined as socially problematic, embarrassment, belief in the sacred nature
      of human sexuality, an anxiety about lack of confidentiality within small
      community groups, and a perceived relationship between cervical smears and sexual
      activity. CONCLUSIONS: Participants strongly preferred that information on
      cervical screening should be transmitted by interpersonal means, though pamphlets
      on screening services were also sought. The women agreed that the preferable role
      of a Pacific Island health professional would be in disseminating information,
      rather than actually serving as a smear-taker. IMPLICATIONS: The need for smear
      taking should not be stereotyped as a 'Pacific problem'. Multi-racial images of
      women should be used in advertising to demonstrate that cervical smears are
      necessary regardless of ethnicity. Information providers need to show great
      sensitivity when providing information relevant to human reproduction or
      sexuality.

PMID- 10083697
TI  - Environmental health officers' understanding about an aboriginal environmental
      health worker program in the Northern Territory.
AB  - OBJECTIVE: To explore environmental health officers' (EHOs) perception that a
      program to train Aboriginal people as environmental health workers in 10 remote
      Northern Territory communities was not operating well. METHOD: Phenomenography,
      an approach within the qualitative domain, was used to explore 15 EHOs'
      understanding about the program during 1996-97. Respondents came from four of the
      Territory's five operational districts. RESULTS: Respondents were unclear about
      worker roles and responsibilities within the program. Perceptions about their own
      skills as trainers in a cross-cultural context inhibited their abilities to
      support the program effectively. CONCLUSIONS: Addressing the support, orientation
      and professional development needs of EHOs will enhance program effectiveness.
      IMPLICATIONS: Support staff should be adequately prepared and trained before a
      new program is commenced.

PMID- 10083698
TI  - Evaluation of doctors' reminders in emergency departments to encourage cervical
      screening.
AB  - OBJECTIVE: To evaluate opportunistic reminders in emergency departments (EDs)
      about cervical smears. METHOD: Five EDs in Sydney in 1995-96 participated in a
      block-randomised control trial, whereby unscreened women at risk for cervical
      cancer who were seen as nonacute cases were allocated either to brief advice at
      the end of the ED consultation to return to their GP for a smear (intervention)
      or usual care (control). Blinded follow-up telephone interviews determined
      women's compliance four weeks later. RESULTS: 217 women at risk for cervical
      cancer presented, of whom 53 (23%) were overdue for a Pap smear (22 intervention
      group; 31 control group). At follow-up, no women in the intervention group had
      had a smear, although 3 (10%) in the control group had (p = 0.25). CONCLUSIONS:
      Opportunities in EDs in NSW for opportunistic reminders are infrequent and, even
      if taken, are unlikely to encourage screening over and above usual care.
      IMPLICATIONS: General practice remains a more effective location for
      opportunistic recruitment, although interventions with hospitalised in-patients
      also show greater promise than reminders in EDs.

PMID- 10083699
TI  - The dissemination of a smoking cessation program to 23 antenatal clinics: the
      predictors of initial program adoption by managers.
AB  - OBJECTIVE: To investigate whether the method of dissemination, antenatal clinic
      practice norms for smoking intervention and subjective evaluation of the
      attributes of a new smoking cessation program are associated with a nurse unit
      manager's initial decision to adopt the new program. METHOD: Twenty-three
      hospital clinics were randomly allocated to two groups which received the program
      either by simple or intensive dissemination methods. Simple dissemination
      involved a mailout of the 'Fresh Start' program and intensive dissemination
      involved a mailout which was enhanced by personal contact with midwifery
      facilitators who provided support and training for the program. It was
      hypothesised that intensive dissemination would improve program adoption compared
      to simple dissemination. It was also hypothesised that managers' perceptions of
      the program and clinic smoking intervention practice norms would predict program
      adoption. A hierarchical regression analysis was used to examine the association
      between these variables and the adoption of program components. RESULTS: The
      results indicated that the method of dissemination and the managers' perceptions
      of the program are significant predictors of program adoption. CONCLUSIONS:
      Although clinic practice norm for smoking cessation education is not a
      significant predictor of program adoption, it appears to mediate managers'
      perceptions of the program.

PMID- 10083700
TI  - Childhood leukaemia and TV towers revisited.

PMID- 10083701
TI  - Sources of tropical health advice used by Australasian scuba divers.

PMID- 10083702
TI  - Hidden hazards around the home--elevated blood lead levels in a female toddler.

PMID- 10083703
TI  - Smoking habits of women who lose a child from SIDS.

PMID- 10083705
TI  - What's in a name?

PMID- 10083704
TI  - Kimberley utility truck passenger fatalities.

PMID- 10083706
TI  - The challenge of biological and chemical weapons.

PMID- 10083707
TI  - Changing trends in barriers to cataract surgery in India.
AB  - Cataract is a major cause of blindness in Asia. Efforts in India to provide
      cataract surgical services have had limited success in reaching the cataract
      blind population. Earlier studies identified the major barriers to cataract
      surgery as poverty, lack of transportation or felt need, or sex related; and the
      critical barriers in rural areas as lack of awareness, difficult access, and
      cost. Compared with these earlier data, the results of the present study in
      Karnataka State indicate a shift in the character of the barriers. They now
      appear to be more related to case selection and service provision. These shifts
      are analysed and alternative strategies to increase the uptake to cataract
      surgery are recommended.

PMID- 10083708
TI  - Human echinococcosis in Bulgaria: a comparative epidemiological analysis.
AB  - The present article describes the importance of human echinococcosis as a public
      health problem in Bulgaria, outlines the control measures carried out and
      evaluates comparatively the situation over three periods spanning 46 years (1950
      1995). During the first period (1950-62), a total of 6469 new surgically
      confirmed cases of hydatid disease were recorded in Bulgaria, with an annual
      incidence of 6.5 per 100,000 population, and the infestation rate in domestic
      animals and dogs was high. Echinococcosis was endemic throughout the country. The
      organization of a control campaign, initiated in 1960, led to a considerable
      improvement in the situation during the second period (1971-82). Morbidity among
      humans gradually decreased, with an average incidence of 2.0 per 100,000, and the
      proportion of infected animals also fell. The distribution of echinococcosis was
      characterized as sporadic or of low endemicity. During the third period (1983
      95), owing to administrative irregularities and economic changes, funds for
      supporting the campaign were reduced and control structures were dismantled. As a
      result, the incidence rose to 3.3 per 100,000. Echinococcosis again became
      endemic, in some regions hyperendemic. The findings provide convincing evidence
      that cessation of control measures or reduction of campaign activity can lead to
      intensification in the transmission of Echinococcus granulosus and to a
      resurgence in echinococcosis to previous levels.

PMID- 10083709
TI  - Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a
      prefilled, single-use injection device.
AB  - Extending immunization coverage to underserved populations will require
      innovative immunization strategies. This study evaluated one such strategy: the
      use of a prefilled, single-use injection device for outreach immunization by
      village midwives. The device, UniJect, is designed to prevent refilling or reuse.
      Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine
      filled UniJect devices were immediately available for outreach. Between July 1995
      and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited
      the homes of newborn infants to deliver hepatitis B vaccine to the infants and
      tetanus toxoid to their mothers. Observations and interviews showed that the
      midwives used the device properly and safely to administer approximately 10,000
      sterile injections in home settings. There were no problems with excessive heat
      exposure during the storage or delivery of vaccine. Injection recipients and
      midwives expressed a strong preference for the UniJect device over a standard
      syringe. Use of the prefilled device outside the cold chain simplified the
      logistics and facilitated the speed and efficiency of home visits, while the
      single-dose format minimized vaccine wastage.

PMID- 10083710
TI  - Influenza vaccination among the elderly in Italy.
AB  - This article surveys the attitudes and perceptions of a random sample of the
      elderly population in three regions of Italy on the use and efficacy of influenza
      vaccine. The data were collected by direct interviews using a standard
      questionnaire. The results show that vaccination coverage against influenza is
      inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in
      the vaccine and disbelief that influenza is a dangerous illness. These data
      emphasize the need for a systematic education programme targeted at the elderly
      and the provision of influenza vaccination, with the increased cooperation of
      general practitioners.

PMID- 10083711
TI  - Measles: effect of a two-dose vaccination programme in Catalonia, Spain.
AB  - The study reports incidences of measles in Catalonia, Spain, as detected by
      surveillance, and analyses the specific characteristics of the outbreaks reported
      for the period 1986-95. Incidences per 100,000 inhabitants were calculated for
      the period 1971-95. The following variables were studied: year of presentation,
      number of cases, median age, transmission setting, cases with a record of
      vaccination and preventable cases. Associations between variables were determined
      using odds ratios (OR). The incidence of measles declined from 306.3 cases in
      1971 to 30.9 in 1995. A total of 50 outbreaks were investigated. The outbreaks
      that occurred in the last two years of the study had a higher likelihood of
      having a transmission setting other than primary school (OR = 3.9); a median case
      age > 10 years (OR = 7.2); and fewer than 6 cases (OR = 2.3). The characteristics
      of recent outbreaks, marked by a rise both in transmission outside the primary
      school setting and in median age, indicate the need for the introduction of a
      specific vaccination programme at the end of adolescence in addition to control
      of school-related outbreaks.

PMID- 10083712
TI  - Can vector control play a useful supplementary role against bancroftian
      filariasis?
AB  - A single campaign of mass treatment for bancroftian filariasis with
      diethylcarbamazine (DEC) in Makunduchi, a town in Zanzibar, United Republic of
      Tanzania, combined with elimination of mosquito breeding in pit latrines with
      polystyrene beads was followed by a progressive decline over a 5-year period in
      the microfilarial rate from 49% to 3%. Evidence that vector control had
      contributed to this long-term decline was obtained by comparison with another
      town, Moga, where a DEC campaign was used without vector control and where
      resurgence of microfilariae could be observed 3-6 years after the campaign. In
      Zanzibar town, treatment of 3844 wet pit latrines and cesspits with polystyrene
      beads reduced the adult mosquito population in houses by about 65%. Supplementary
      treatment of open drains and marshes with Bacillus sphaericus produced little or
      no additional reduction compared to a sector of the town where only pit treatment
      with polystyrene was carried out. The cost and effort of achieving the 65%
      reduction in mosquito population could hardly be justified for its impact on
      filariasis alone, but its noticeable impact on biting nuisance might help to gain
      community support for an integrated programme.

PMID- 10083713
TI  - Long-term morbidity and mortality following hypoxaemic lower respiratory tract
      infection in Gambian children.
AB  - Acute lower respiratory infections (ALRI) are the main cause of death in young
      children worldwide. We report here the results of a study to determine the long
      term survival of children admitted to hospital with severe pneumonia. The study
      was conducted on 190 Gambian children admitted to hospital in 1992-94 for ALRI
      who survived to discharge. Of these, 83 children were hypoxaemic and were treated
      with oxygen, and 107 were not. On follow-up in 1996-97, 62% were traced. Of the
      children with hypoxaemia, 8 had died, compared with 4 of those without. The
      mortality rates were 4.8 and, 2.2 deaths per 100 child-years of follow-up for
      hypoxaemic and non-hypoxaemic children, respectively (P = 0.2). Mortality was
      higher for children who had been malnourished (Z-score < -2) when seen in
      hospital (rate ratio = 3.2; 95% confidence interval (CI) = 1.03-10.29; P =
      0.045). Children with younger siblings experienced less frequent subsequent
      respiratory infections (rate ratio for further hospitalization with respiratory
      illness = 0.15; 95% CI = 0.04-0.50; P = 0.002). Children in Gambia who survive
      hospital admission with hypoxaemic pneumonia have a good prognosis. Survival
      depends more on nutritional status than on having been hypoxaemic. Investment in
      oxygen therapy appears justified, and efforts should be made to improve nutrition
      in malnourished children with pneumonia.

PMID- 10083714
TI  - The efforts of WHO and Pugwash to eliminate chemical and biological weapons--a
      memoir.
AB  - The World Health Organization and the Pugwash Conferences on Science and World
      Affairs (Nobel Peace Prize 1995) have been involved in questions concerning
      chemical and biological arms since the early 1950s. This memoir reviews a number
      of milestones in the efforts of these organizations to achieve the elimination of
      these weapons through international treaties effectively monitored and enforced
      for adherence to their provisions. It also highlights a number of outstanding
      personalities who were involved in the efforts to establish and implement the two
      major treaties now in effect, the Biological Weapons Convention of 1972 and the
      Chemical Weapons Convention of 1993.

PMID- 10083715
TI  - Health expenditure and finance: who gets what?
AB  - The methods used in South Africa's first comprehensive review of health finance
      and expenditure are outlined. Special measures were adopted to make the process
      acceptable to all concerned during a period of profound political transition. The
      estimation of indicators of access to public sector resources for districts
      sorted by per capita income allowed the health care problems of disadvantaged
      communities to be highlighted.

PMID- 10083716
TI  - Integrating homoeopathy in health systems.
AB  - Homoeopathy is a therapy which involves many components and three main agents:
      the patient, with his or her condition and personal characteristics; the
      medication used, with its composition and manufacturing procedure; and the
      physician, with his or her approach to treatment and concepts of health. The
      development of research and evaluation structures, combined with a critical
      education in the discipline, would help to improve practices and define
      homoeopathy's potential role in relation to the other therapies, both
      conventional and unconventional, used in Western health systems.

PMID- 10083717
TI  - Revolving drug funds: a step towards health security.
AB  - The establishment of a revolving drug fund project in Viet Nam is described and
      the factors responsible for its success are considered. As well as being a tool
      for cost recovery a revolving drug fund can serve as an entry point for
      strengthening health care and improving health security at local and district
      level.

PMID- 10083718
TI  - Food safety training for nutritionists.
AB  - A course on food safety for nutritionists has been developed in Indonesia through
      collaboration between government, industry, academia and international agencies.
      By teaching the basic principles of the subject it equips the participants to
      recommend foods that are safe as well as nutritious.

PMID- 10083719
TI  - Light on population health status.
AB  - A new approach to illustrating and analysing health status is presented which
      allows comparisons of various aspects of health in a population at different
      times and in different populations during given periods. Both quantitative and
      qualitative elements can be represented, the impact of interventions can be
      monitored, and the extent to which objectives are achieved can be assessed. The
      practical application of the approach is demonstrated with reference to the
      health profiles to Tunisia in 1966 and 1994.

PMID- 10083720
TI  - Health expectancy indicators.
AB  - An outline is presented of progress in the development of health expectancy
      indicators, which are growing in importance as a means of assessing the health
      status of populations and determining public health priorities.

PMID- 10083721
TI  - A management information system for nurse/midwives.
AB  - The experiences of nurse/midwives with a simple management information system in
      the private sector are reported from four facilities in Nigeria. When such a
      system is being introduced, special attention should be given to strengthening
      the ability of health workers to record and collate data satisfactorily.

PMID- 10083722
TI  - A strategy for reducing maternal mortality.
AB  - A confidential system of enquiry into maternal mortality was introduced in
      Malaysia in 1991. The methods used and the findings obtained up to 1994 are
      reported below and an outline is given of the resulting recommendations and
      actions.

PMID- 10083723
TI  - Poliovirus vaccine: commentary.

PMID- 10083724
TI  - Live, orally given poliovirus vaccine. Effects of rapid mass immunization on
      population under conditions of massive enteric infection with other viruses.
      1960.

PMID- 10083725
TI  - Swedes break record for giving up smoking.

PMID- 10083726
TI  - Financial crisis blamed for cutbacks in vaccination.

PMID- 10083727
TI  - Public health in a new era.

PMID- 10083728
TI  - Salt iodization in Bangladesh--problems and a suggestion.

PMID- 10083729
TI  - A novel therapeutic trial of homogentisic aciduria in a murine model of
      alkaptonuria.
AB  - Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic
      aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid
      1,2-dioxygenase has recently been confirmed at the molecular level, no effective
      treatment regimen has yet been developed for this disorder. In the present study,
      2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent
      inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation
      of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible
      therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary
      output of homogentisic acid in a murine model of alkaptonuria that had been
      created with ethylnitrosourea. These findings suggest that NTBC may be the first
      potent pharmacotherapeutic agent for alkaptonuria.

PMID- 10083730
TI  - Clinical applications of two-color telomeric fluorescence in situ hybridization
      for prenatal diagnosis: identification of chromosomal translocation in five
      families with recurrent miscarriages or a child with multiple congenital
      anomalies.
AB  - Two-color fluorescence in situ hybridization (FISH) analysis using human
      chromosome arm-specific telomeric probes (telomeric probes) was used successfully
      to detect each derivative chromosome of a translocation carrier in five couples
      who requested a prenatal diagnosis in future pregnancies. Most of the human
      chromosome terminal bands are G-band-negative, and even FISH analysis using whole
      chromosome painting (wcp) probes are often of insufficient complexity to detect
      subtle chromosomal changes. A complete set of human telomeric probes was
      developed to improve the sensitivity of diagnosis of microdeletions or other
      cryptic rearrangements in telomeric regions. Two-color telomeric FISH was the
      only possible method for precise prenatal diagnosis of one of the couples,
      because the carrier's chromosomal aberration was too subtle to be detected by wcp
      FISH or conventional methods. We have demonstrated that two-color telomeric FISH
      has the potential to be a powerful new tool in the detection of cryptic
      chromosomal rearrangements involving telomeric regions in prenatal diagnosis
      precisely and in time.

PMID- 10083731
TI  - Novel mutations, including the second most common in Japan, in the beta
      hexosaminidase alpha subunit gene, and a simple screening of Japanese patients
      with Tay-Sachs disease.
AB  - Two novel mutations of the beta-hexosaminidase alpha subunit gene were identified
      in Japanese patients with the infantile form of Tay-Sachs disease. One mutation
      was a one-base deletion at nt613C, which generated a stop codon at two codons
      downstream, in three unrelated patients. The other mutation was a one-base
      substitution of G-to-A at IVS 5, +1, which caused a splicing abnormality, in one
      patient. A missense mutation of R170W, which has already been reported in other
      ethnic groups, was also newly identified in one patient. In 1993, the most common
      mutation (IVS 5, -1G-->T) in Japanese patients with Tay-Sachs disease was
      reported as the major mutation in Japan accounting for 80% of 56 mutant alleles
      from 28 unrelated patients. The deletion of nt613C was the second most common
      mutation, accounting for 5% of the mutant alleles. The previously reported
      mutation IVS 5, -1G-->T and the nt613C deletion found in this study together
      accounted for 85% of the mutations causing Tay-Sachs disease among Japanese.
      Since these two mutations were located in or close to exon 6 and since they
      abolish Fok I (IVS 5, -1G-->T) and Sfa NI (nt613C deletion) restriction sites,
      respectively, they were screened rapidly by single polymerase chain reaction
      followed by digestion with these enzymes.

PMID- 10083732
TI  - Ret/PTC3 is the most frequent form of gene rearrangement in papillary thyroid
      carcinomas in Japan.
AB  - Rearrangements of the RET and TRK proto-oncogenes, which generate fusion
      oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations.
      To determine the spectrum of gene rearrangements in Japanese patients, we
      systematically examined 40 papillary thyroid carcinomas for all possible types of
      gene fusion events involving RET or TRK genes. RET rearrangements were found in
      ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3
      in six, and a novel RET rearrangement in the remaining patient. In this last
      patient, the 5' novel sequence was fused in-frame to the RET amino acid sequence;
      thus, the fusion gene may encode a protein with a RET kinase domain at the
      carboxy terminus. The RET gene was fused to 5' donor sequences at the beginning
      of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found
      in this panel of carcinomas. Our results indicated that constitutive activation
      of the RET by gene rearrangement is a frequent mechanism of papillary thyroid
      carcinogenesis in Japanese adults.

PMID- 10083733
TI  - Germline mutations of the APC gene in Korean familial adenomatous polyposis
      patients.
AB  - We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated
      Korean patients with familial adenomatous polyposis (FAP) for identification of
      germline adenomatous polyposis coli (APC) gene mutations. We adopted both single
      strand conformation polymorphism (SSCP) analysis and a method of analysis
      involving the reverse transcription-polymerase chain reaction (RT-PCR) followed
      by a protein truncation test (PTT). DNA sequencing confirmed all alterations
      represented by aberrant bands. Germline mutations were identified in 38 patients
      (61%). Nineteen of the detected mutations were presumed to be novel, thus
      emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients.
      In the initial 48 patients, SSCP analysis was followed by PTT for those patients
      for whom no detectable mutations were found by SSCP. Using this combined
      approach, we identified germline APC gene mutations in 29 of the 48 FAP patients
      (60%), including 6 patients in whom SSCP analysis failed to distinguish the
      mutant allele. In the 14 later patients, we identified truncating mutations in 9
      patients (64%) using PTT only. Our results confirm that the mutation detection
      rate with PTT was superior to that with SSCP, and suggest that PTT would be a
      more practical screening method to detect germline mutations of the APC gene in
      FAP patients.

PMID- 10083734
TI  - Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation
      of the C9 gene in Japan.
AB  - Deficiency of the ninth component of human complement (C9) is the most common
      complement deficiency in Japan, with an incidence of approximately one homozygote
      in 1000, but is very rare in other countries. Genetic analyses of Japanese C9
      deficiency have shown that a C-to-T transition leading to TGA stop codon for
      Arg95 in exon 4 of the C9 gene (Arg95Stop) is common in Japanese C9 deficiency.
      To determine the prevalence of heterozygous carriers of the Arg95Stop mutation in
      a Japanese population, we collected DNA samples from 300 individuals in two of
      the four main islands of Japan. Heterozygote detection was performed with an
      allele-specific polymerase chain reaction (PCR) system designed to detect
      exclusively only one of the normal and mutant alleles, followed by confirmation
      with PCR/single-strand conformation polymorphism (SSCP) analysis and direct
      sequencing. Twenty individuals were heterozygous for the Arg95Stop mutation. None
      was homozygous. The prevalence of carriers of the Arg95Stop mutation was 6.7%
      (20/300). An estimated frequency (0.12%) of complete C9 deficiency due to
      homozygous Arg95Stop mutation was consistent with frequencies determined by
      serological studies.

PMID- 10083735
TI  - Isolation and chromosomal assignment of human genes encoding cofactor of LIM
      homeodomain proteins, CLIM1 and CLIM2.
AB  - Cofactors of LIM homeodomain proteins (CLIM) are transcriptional activators that
      associate with the LIM homeoproteins and coordinate transcription. LIM
      homeoproteins and CLIMs are involved in a variety of developmental processes. Two
      CLIMs, CLIM1 and CLIM2, have been identified in the mouse. Here we report the
      isolation of human CLIM1 and CLIM2 cDNAs and the determination of their
      chromosome locations by using a human-rodent monochromosomal hybrid cell panel
      and a radiation hybrid mapping panel. The proteins deduced from human CLIM1 and
      CLIM2 cDNAs were composed of 373 and 375 amino acids, respectively, and had 97.3%
      and 98.7% amino acid identity, respectively, to their mouse counterparts. Human
      CLIM1 and CLIM2 proteins were 75.5% identical. Human CLIM1 and CLIM2 genes were
      mapped to the chromosome on 4p15.3 and 10q24-q25 regions, respectively. Mapping
      of a pair of developmentally important genes may provide new clues to the
      understanding of genetic disorders caused by these chromosome regions.

PMID- 10083736
TI  - Isolation and characterization of a novel serine threonine kinase gene on
      chromosome 3p22-21.3.
AB  - Through large-scale DNA sequencing of a genomic region on chromosome 3p22-p21.3,
      we isolated a novel gene encoding a 527-amino-acid protein. Its 18 exons spanned
      a genomic region of about 90 kilobases, and the 4536-nucleotide cDNA contained an
      open reading frame of 1581 base pairs. The gene was expressed in all 16 human
      tissues examined by Northern blotting. The amino acid sequence of the predicted
      protein was 39% identical to that of human SOK1 (Ste20/oxidant stress response
      kinase-1), a molecule that is activated by oxidative stress. In view of its
      significant similarity to SOK1, we suspect that the novel gene, which we named
      OSR1, is a member of the SOK family of kinases in terms of function.

PMID- 10083737
TI  - A novel human gene whose product shares significant homology with the bovine
      brain-specific protein p25 on chromosome 5p15.3.
AB  - Here, we report on the sequence features and chromosomal location of a novel
      human gene which shares significant homology with the bovine brain-specific
      protein p25. Based on polymerase chain reaction analysis with a human/rodent
      monochromosomal hybrid cell panel and a radiation hybrid panel, the gene was
      mapped on to p15.3 region of chromosome 5.

PMID- 10083738
TI  - A novel nonsense mutation of the PEX7 gene in a patient with rhizomelic
      chondrodysplasia punctata.
AB  - Mutations in the PEX7 gene encoding a peroxisome targeting signal 2 (PTS2) were
      identified in two patients with rhizomelic chondrodysplasia punctata (RCDP). A 7
      year-old girl, the first Japanese individual to be diagnosed biochemically as a
      case of RCDP, had a novel nonsense mutation, R232ter, in the PEX7 gene, which had
      been inherited from her consanguineous parents. Another patient, a Chilean boy
      with RCDP, had compound heterozygous mutations of PEX7, L292ter and A218V, both
      of which have been documented. R232ter, which deletes all of the last two WP40
      repeats in the PEX7 gene, is sufficient to inactivate functions of the PEX7 gene.

PMID- 10083739
TI  - Familial isolated noncompaction of ventricular myocardium.
AB  - We report a family in which two male sibs were affected with isolated
      noncompaction of ventricular myocardium (INVM). The familial occurrence of INVM
      suggests a genetic basis. We review the literature of familial and nonfamilial
      cases and discuss the inheritance pattern of INVM.

PMID- 10083740
TI  - Isolation and radiation hybrid mapping of a highly polymorphic CA repeat sequence
      at the human nuclear factor kappa-beta subunit 1 (NFKB1) locus.
AB  - The transcriptional factor nuclear factor kappa-beta (NFKB) consists of a
      multicomponent protein complex that plays a major role in the regulation of many
      viral and cellular genes. The NFKB complex has two alternative DNA binding
      subunits. We isolated a polymorphic dinucleotide (CA) repeat sequence from a
      genomic clone containing the NFKB subunit 1 (NFKB1) gene located at 4q23-24. High
      heterozygosity (0.813) makes this polymorphism a useful marker in the genetic
      study of disorders affecting the immune response and cell differentiation.

PMID- 10083741
TI  - A Gln/Arg polymorphism at codon 349 of the hBUBR1 gene.
AB  - We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene,
      encoding a protein kinase required for spindle assembly checkpoint function. The
      observed heterozygosity was estimated to be 45% in the Japanese population. This
      polymorphism may be helpful for genetic studies of many cancer types in which
      chromosomal instability is observed.

PMID- 10083742
TI  - Isolation and mapping of a polymorphic CA repeat sequence at the human VRK1
      locus.
AB  - VRK1 is a novel human putative serine/threonine kinase, and is located on
      chromosome 14 at band q32 where an autosomal recessive congenital microphthalmia
      (CMIC) is mapped. We isolated a polymorphic dinucleotide CA repeat marker from a
      genomic clone containing the human VRK1 gene. This polymorphism will be useful in
      genetic studies of disorders localized at the 14q32 region, such as CMIC.

PMID- 10083743
TI  - A novel Sac I RFLP in the 3' untranslated region of the myotonin protein kinase
      gene.
AB  - We found a novel Sac I polymorphism downstream of CTG repeats in the 3'
      untranslated region of the myotonin protein kinase (MT-PK) gene. A C to G
      transition at nucleotide 13,590 in the gene was revealed by Southern blotting and
      confirmed by sequencing analyses. The allelic frequency of the C:G polymorphism
      in 63 unrelated Japanese individuals was estimated to be 0.98:0.02. When Southern
      blotting is employed in the analysis of the CTG repeat length in the MT-PK gene,
      this Sac I polymorphism should be taken into consideration.

PMID- 10083744
TI  - The human regulator of G-protein signaling protein 6 gene (RGS6) maps between
      markers WI-5202 and D14S277 on chromosome 14q24.3.
AB  - The recently discovered regulators of G-protein signaling proteins, termed the
      RGS family, have been shown to modulate the functioning of G-proteins by
      activating the intrinsic guanosine triphosphatase (GTPase) activity of the alpha
      subunits. Here, we report the chromosomal location and tissue expression of the
      human regulator of RGS6 gene. The messenger RNA was ubiquitously expressed in
      various tissues. Polymerase chain reaction (PCR)-based analysis with a
      human/rodent monochromosomal hybrid panel and a radiation hybrid panel indicated
      that the gene was mapped between genetic markers WI-5202 and D14S277 on
      chromosome 14q24.3 region.

PMID- 10083745
TI  - Chromosomal assignment of a human apoptosis-associated tyrosine kinase gene on
      chromosome 17q25.3 by somatic hybrid analysis and fluorescence in situ
      hybridization.
AB  - Here, we report on the chromosomal location of the human apoptosis-associated
      tyrosine kinase gene. Based on polymerase chain reaction analysis with a
      human/rodent monochromosomal hybrid cell panel and fluorescence in situ
      hybridization, the gene was mapped on 25.3 region of chromosome 17.

PMID- 10083746
TI  - Single-strand conformation polymorphism analysis for identification of four
      members of the Anopheles funestus (Diptera: Culicidae) group.
AB  - Members of the Anopheles funestus Giles group are difficult to identify because
      of the morphological overlap that exists within the group. This inability to
      distinguish species, as well as the fact that the species vary in their behavior
      and biting preferences, complicate the successful planning and maintaining of
      malaria control programs. In this article we discuss the use of a single-strand
      conformation polymorphism (SSCP) assay to distinguish 4 members of the An.
      funestus group collected at 10 different localities in Africa. rDNA genes differ
      at numerous sites among closely related species. Using conserved primers, the D3
      domain in the 28S gene was amplified, electrophoresed on SSCP gels, and species
      specific patterns were observed. Intraspecific variation was detected in An.
      funestus specimens from East and West Africa. Analyzing 108 An. funestus, 78 An.
      vaneedeni Gillies & Coetzee, 21 An. rivulorum Leeson, and 2 An. lessoni Evans, we
      concluded that SSCPs can be used successfully as a molecular tool for the
      identification of these species.

PMID- 10083747
TI  - Importance of insects in asthma.

PMID- 10083748
TI  - New cytotype in the Simulium metallicum complex (Diptera: Simuliidae) from
      Cundinamarca, Colombia.
AB  - Polytene chromosomes (n = 108) and morphology (n = 22) of Simulium metallicum
      Bellardi were described from larvae collected in different localities in
      Cundinamarca, Colombia, and compared with the standard polytene chromosome
      banding patterns of S. metallicum A. Polytene chromosomes of S. metallicum from
      Cundinamarca were characterized by a fixed inversion on the IIL chromosome arm
      (IIL-22), by 2 sex-linked inversions (IIL-24 and IIL-25), 6 floating inversions,
      and a heteroband in the IIIS chromosome arm. This taxon was considered to be a
      cytotype distinct from the 11 members of the S. metallicum complex from Central
      and South America, and we propose here the name S. metallicum L, following the
      convention for naming cytotypes in this species complex. There were slight larval
      morphological differences between S. metallicum from Cundinamarca and S.
      metallicum A and S. horacioi Okazawa & Onishi (or S. metallicum H).

PMID- 10083749
TI  - Rubidium marking of Anopheles stephensi (Diptera: Culicidae).
AB  - Immature Anopheles stephensi Liston were reared in untreated water and water
      containing eight 2-fold dilutions of rubidium (Rb) from 1,000 to 7.8 ppm to
      determine the concentration that allowed reliable detection and produced the
      least toxic effects as measured by adult emergence, weight, and survival. The
      amount of Rb detected in mosquitoes increased positively with increasing
      concentrations in the rearing water. Concentrations > or = 31.2 ppm Rb in the
      rearing water provided high and consistent detection levels of > or = 3,500 ppm
      Rb/mg of adult mosquito. There were no adverse effects of Rb on the weights of
      mosquitoes. However, increased Rb concentrations in the rearing water were
      associated with decreased emergence and survival. After 8 d, percentage emergence
      from Rb concentrations of 0-31.2 ppm was > or = 50%. At day 21, Rb concentrations
      of 0-31.2 ppm showed < or = 29% reduction of female survival compared with
      controls. The recommended concentration for reliable Rb detection with minimal
      toxic effects in An. stephensi was 32 ppm.

PMID- 10083750
TI  - Comparison of plant products and pyrethroid-treated bed nets for protection
      against mosquitoes (Diptera: Culicidae) in Guinea Bissau, West Africa.
AB  - In Guinea Bissau, West Africa, the shrub Hyptis suaveolens Poit. (Lamiaceae) and
      smoke of the bark of the tree Daniellia oliveri Rolfe (Caesalpiniaceae)
      traditionally are used to reduce numbers of mosquitoes indoors at night. We
      recorded the numbers of mosquitoes in the bedrooms of 30 households in a rural
      village, Mandinka-Ra in central Guinea Bissau. Each household was provided with
      bed nets and allocated randomly to 1 of 6 treatments as follows: (1) lambda
      cyhalothrin-treated bed nets (10 mg/m2), (2) permethrin-treated bed nets (500
      mg/m2), (3) burning of H. suaveolens, (4) burning of the bark of D. oliveri, (5)
      fresh H. suaveolens, and (6) control group using untreated bed nets and no plant
      products. In treatment groups 1-4, the mean number of mosquitoes was
      significantly less than the mean of the control. These results indicated that the
      use of burning H. suaveolens or D. oliveri indoors at night repelled endophagic
      mosquitoes and may contribute significantly to reducing the prevalence of
      diseases caused by pathogens transmitted by house-frequenting, nocturnally blood
      feeding arthropods.

PMID- 10083751
TI  - Chorion formation and ultrastructure of the egg of the cat flea (Siphonaptera:
      Pulicidae).
AB  - Oocyte development in adult female cat fleas, Ctenocephalides felis (Bouche), was
      studied by light and electron microscopy to determine the formation and
      ultrastructural morphology of the eggshell. As oocytes develop, somatic follicle
      cells from the lining of the ovariole migrate around the oocytes. The follicle
      cells produce electron-dense granules that form the vitelline membrane around the
      developing oocyte. Subsequently, electron-lucent granules containing an electron
      dense core (precursors of the chorion) are produced from the rough endoplasmic
      reticulum that appear as dilated and clear linear clefts in the cytoplasm of the
      follicle cells. Exocytosis and coalescence of the granules around the oocyte as
      the follicle cells disintegrate give rise to the chorion. The chorion was found
      to consist of 4 distinct layers. The external surface of the egg shell consists
      of a particulate layer approximately 760 nm thick, composed of an electron-lucent
      layer of widely dispersed granules. Embedded in this layer are electron-dense
      spheres that project above the surface of this granular layer. Beneath this
      outermost layer is a band of electron-dense material, consisting of densely
      packed granules and is half as thick as the outer particulate layer. The 3rd
      layer consists of relatively thick, weakly laminated chorion, with a felt-like
      appearance due to a meshwork of microfibrils. Projections of this network of
      microfibrils form pillars that attach this layer to a thin relatively compact 4th
      or basal layer. The pillars and the air-filled cavities lying between the 3rd and
      4th chorionic layers constitute the chorionic meshwork known as the palisades or
      trabecular layer that form the major respiratory organ of the eggshell. The
      trabecular layer is connected to the external environment by means of the lateral
      and anterior aeroplyes. The vitelline membrane lies between the chorion and
      oocyte and is a granular, uniform, moderately electron-dense layer measuring
      approximately 260 nm thick. The micropyle at the posterior of the flea egg
      consists of a rosette of 50-80 apertures and possesses an internal electron-dense
      plug between the chorion and the vitelline membrane. An aeropyle at the anterior
      end of the egg consists of a rosette of 40-50 apertures. An inconspicuous
      aeropyle appears as a cluster of hexagonal or polygonal-shaped plaques on the
      lateral surface of the chorion. Each plaque contains 3-8 pores.

PMID- 10083752
TI  - Electroantennogram and oviposition bioassay responses of Culex quinquefasciatus
      and Culex tarsalis (Diptera: Culicidae) to chemicals in odors from Bermuda grass
      infusions.
AB  - Odors were collected from the headspace above fermented infusions of Bermuda
      grass, which commonly are used as attractants in traps for gravid mosquitoes.
      Coupled gas chromatography-electroantennogram detection (GC-EAD) was used to
      identify 9 compounds (phenol, p-cresol, 4-ethylphenol, indole, 3-methylindole,
      nonanal, 2-undecanone, 2-tridecanone, naphthalene) from odor extracts that
      elicited significant antennal responses from antennae of gravid female Culex
      quinquefasciatus Say and Culex tarsalis Coquillett mosquitoes. Several of these
      compounds at appropriate concentrations were weakly attractive to gravid female
      mosquitoes in laboratory bioassays and/or stimulated more oviposition than water
      controls. In addition, dimethyltrisulfide, a significant component of odor
      extract which did not elicit strong responses from female mosquito antennae in GC
      EAD assays, also appeared to stimulate oviposition at 1 concentration. A
      reconstituted blend of the 10 compounds resulted in much stronger and more
      consistent responses than individual compounds. The blend was attractive to
      gravid Cx. quinquefasciatus and enhanced oviposition over a range of
      concentrations spanning 3 orders of magnitude. One concentration of the blend
      also attracted gravid Cx. tarsalis and enhanced oviposition. However, at the
      highest concentration tested, the blend was repellent to both species. Overall,
      these studies demonstrated that gravid mosquitoes are attracted to oviposition
      sites by blends of compounds rather than by individual chemicals, and that the
      concentration of compounds in the odor is a critical factor in determining
      whether responses are positive (attractive, stimulatory) or negative (repellent,
      deterrent).

PMID- 10083753
TI  - Demodex gatoi: new species of hair follicle mite (Acari: Demodecidae) from the
      domestic cat (Carnivora: Felidae).
AB  - Demodex gatoi sp. nov. is described in all its life stages from the domestic cat.
      The host was diagnosed with presumptive feline acquired immunodeficiency syndrome
      and harbored enormous numbers of both D. gatoi and D. cati Hirst, 1919. Unlike D.
      cati, which inhabits the hair follicles, D. gatoi resides on the epidermal
      surface. More than half of the D. gatoi population sampled was made up of ova
      indicating rapid population growth.

PMID- 10083754
TI  - Blood feeding and oviposition by Culex nigripalpus (Diptera: Culicidae) before,
      during, and after a widespread St. Louis encephalitis virus epidemic in Florida.
AB  - A widespread epidemic of St. Louis encephalitis (SLE) virus was reported from
      central Florida from late July through December 1990 with 226 clinical cases and
      11 deaths in humans. The abundance of blood-fed and gravid Culex nigripalpus
      Theobald females, the vector of SLE in Florida, was monitored at a resting site
      in Indian River County, FL, for the 3 yr before the epidemic, the epidemic year,
      and for 1 yr following the epidemic. Each study year was divided into four 3-mo
      periods that depict the subtropical SLE transmission cycle; a January-March
      maintenance phase, an April-June amplification phase, a July-September early
      transmission phase, and an October-December late transmission phase. The
      abundance of blood-fed and gravid females was significantly greater during the
      amplification, early transmission, and late transmission phases of the 1990 SLE
      epidemic when compared with the 3 pre-epidemic years. Throughout the study, Cx.
      nigripalpus blood feeding and oviposition was driven by epic (> 50 mm) rainfall
      events. The abundance of gravid females decreased, whereas the number of blood
      fed females increased following heavy rainfalls. Epizootic and epidemic
      transmission of SLE to sentinel chickens and humans in Indian River County was
      greatest immediately following heavy rainfalls that synchronized Cx. nigripalpus
      oviposition and blood feeding.

PMID- 10083755
TI  - Comparative vector competence of Dermacentor variabilis and Ixodes scapularis
      (Acari: Ixodidae) for the agent of human granulocytic ehrlichiosis.
AB  - Vector competence of Ixodes scapularis Say and Dermacentor variabilis Say for the
      agent of human granulocytic ehrlichiosis (HGE) was compared. Five white-footed
      mice, Peromyscus leucopus Rafinesque, were inoculated intra-peritoneally with
      blood from a mouse infected with the agent of HGE. Approximately 100 I.
      scapularis and D. variabilis larvae were placed on each mouse and allowed to feed
      to repletion. Fed larvae were collected, separated according to species and
      allowed to molt to nymphs. Twenty-six per cent of I. scapularis (34/131) and 11%
      of D. variabilis (11/96) tested positive for the agent of HGE by polymerase chain
      reaction (PCR) after molting to nymphs. Positive I. scapularis nymphs transmitted
      the agent of HGE to P. leucopus mice in 5 of 5 trials. In contrast, the positive
      D. variabilis nymphs did not transmit the agent of agent of HGE in any of 6
      trials. In a 2nd experiment, 3 P. leucopus mice were infested with I. scapularis
      nymphs that were infected with the agent of HGE. All 3 mice became infected with
      the agent of HGE and approximately 300 D. variabilis larvae were placed on each
      mouse and allowed to feed to repletion. Larvae were collected and allowed to molt
      to nymphs as before. Approximately 8% (5/60) of the nymphs became positive for
      the agent of HGE as determined by PCR. Twenty-five of these nymphs were then
      placed on each of 9 P. leucopus mice and allowed to feed to repletion. Evidence
      of transmission was not observed in any of 9 mice exposed to D. variabilis
      nymphs. These results demonstrate that although I. scapularis is a competent
      vector of the agent of the HGF, D. variabilis is not.

PMID- 10083756
TI  - Experimental infection and transmission of Barmah Forest virus by Aedes vigilax
      (Diptera: Culicidae).
AB  - Aedes vigilax (Skuse) mosquitoes colonized from Townsville, Queensland,
      Australia, were fed on blood containing Barmah Forest virus (BF) isolated from
      the same species. The colony was susceptible to infection, with an ID50 of
      10(2.6) CCID50 per mosquito. Infection and transmission rates for mosquitoes fed
      10(3.5) CCID50 virus per mosquito varied from 58 to 100% and 36 to 100%,
      respectively, between days 3 and 13 after infection. Titers in infected
      mosquitoes were high by 5 d after infection and did not vary substantially
      thereafter. Virus transmission to suckling mice occurred from 3 d after
      infection. This work establishes that Ae. vigilax is a competent vector of BF.

PMID- 10083757
TI  - Novel Ehrlichia organism (Rickettsiales: Ehrlichieae) in white-tailed deer
      associated with lone star tick (Acari: Ixodidae) parasitism.
AB  - Polymerase chain reaction (PCR) evidence of a novel Ehrlichia organism was found
      recently in wild white-tailed deer, Odocoileus virginianus Zimmermann, and lone
      star ticks, Amblyomma americanum L., from the southeastern United States. To
      evaluate whether lone star tick parasitism was associated with the presence of
      this novel Ehrlichia organism in deer, 2 retrospective studies were conducted
      using specific nested PCR to test archived deer serum samples. The 1st study of
      150 serum samples collected from a single deer population over a 15-yr period
      examined the temporal association between the presence of the Ehrlichia organism
      in deer and parasitism by lone star ticks. The deer Ehrlichia was not detected in
      serum samples collected before 1986, when lone star ticks were absent or rare,
      but was detected in samples collected in 1986 and every year thereafter, when
      lone star ticks became increasingly abundant. In the 2nd study, serum samples
      from 120 deer from 24 sites in 14 southeastern states were tested to evaluate if
      a site-specific, spatial association existed between the presence of the deer
      Ehrlichia and lone star ticks. All 60 serum samples from the 12 deer populations
      without evidence of lone star tick infestation were negative for the deer
      Ehrlichia, whereas 83% of the 12 populations infested by lone star ticks had PCR
      evidence of infection. These data suggest that lone star ticks may be a vector of
      the deer Ehrlichia; however, they do not preclude the involvement of other
      arthropods in maintaining infection with this organism in deer populations.

PMID- 10083758
TI  - Taxonomic review of Physconelloides (Phthiraptera: Philopteridae) from the
      Columbiformes (aves), including descriptions of three new species.
AB  - We provide a comprehensive taxonomic review of Physconelloides, a genus of
      ischnoceran chewing lice found on pigeons and doves (Columbiformes). Thirteen
      previously known Physconelloides species are redescribed and 16 new synonymies
      are designated: P. rubripes Carriker, P. rubripes longulus Tendeiro, P.
      piotrowskii Tendeiro and P. auritae Tendeiro are synonyms of P. zenaidurae
      (McGregor); P. recurvatus Eichler, P. chocoensis Carriker and P. montana Carriker
      are synonyms of P. ceratoceps Ewing; P. silvestris Tendeiro is a synonym of P.
      perijae Carriker; P. keleri Kaddou and P. branderi Kaddou are synonyms of P.
      spenceri Emerson and Ward; P. wolfdietrichi Kaddou is a synonym of P. anolaimae
      Carriker; and Goniocotacanthus mattogrossensis Guimaraes, P. passerinae Emerson,
      P. eurysema pretiosa Carriker, P. talpacoti Carriker and P. picuii Tendeiro are
      synonyms of P. eurysema (Carriker). Three new species are also described: P.
      moyeri (type host Geotrygon linearis), P. johnsoni (type host Columbina passerina
      bahamensis), and P. robbinsi (type host Metriopelia ceciliae). A key is provided
      for identification of the 16 recognized species.

PMID- 10083759
TI  - Outdoor survival and development of immature cat fleas (Siphonaptera: Pulicidae)
      in Florida.
AB  - In north-central Florida, cat flea, Ctenocephalides felis felis Bouche, larvae
      survived outdoors year round. Their survival was greatest (up to 84.6%) outdoors
      in the fall, from September to November, when both temperatures and relative
      humidities were moderate. Female cat fleas developed faster than males.
      Development times for flea larvae were shortest (20-24 d) in June and July. From
      January to March, flea larval mortality was highest (91.7-100%) and development
      times the longest (36-50 d) outdoors. This was the result of low temperatures and
      low relative humidities associated with the passage of cold fronts during this
      time of year. Flea larvae survived light frosts in protected microhabitats such
      as inside a doghouse and under a mobile home.

PMID- 10083760
TI  - Notes on responses of blacklegged ticks (Acari: Ixodidae) to host urine.
AB  - In laboratory bioassays under conditions of high humidity, host-seeking female
      black-legged ticks, Ixodes scapularis Say, avoided urine of reproductively active
      male and nonestrous female white-tailed deer, Odocoileus virginianus
      (Zimmermann), the principal host species of the adult stage. At 50% RH, female I.
      scapularis did not avoid urine from male and female deer. Larval and nymphal I.
      scapularis did not exhibit an arrestment response to urine from male and female
      white-footed mice, Peromyscus leucopus (Rafinesque), a major host for immature
      blacklegged ticks. These results suggest that under some conditions, urine from 2
      principal host species in certain physiological states does not provide
      kairomonal cues that aid I. scapularis in contacting these host species.

PMID- 10083761
TI  - Infection of Ixodes ricinus (Acari: Ixodidae) by Borrelia burgdorferi sensu lato
      in North Africa.
AB  - Free-living adult Ixodes ricinus L, were collected in Amdoun, situated in the
      Kroumiry mountains in northwestern Tunisia (North Africa). Using direct
      fluorescence antibody assay, the infection rate of field-collected I. ricinus by
      Borrelia burgdorferi sensu lato was 30.5% (n = 72). No difference in infection
      rate was observed between male and female ticks. Spirochetes that had been
      isolated from I. ricinus from Ain Drahim (Kroumiry Mountains) in 1988 were
      identified as Borrelia lusitaniae (formerly genospecies PotiB2). This is the
      first identification of a genospecies of Borrelia burgdorferi sensu lato from the
      continent of Africa.

PMID- 10083762
TI  - Secretion of acute-phase proteins before and after hepatocellular carcinoma
      resection.
AB  - Hepatocyte growth factor (HGF), interleukin-6 (IL-6), and C-reactive protein
      (CRP) are acute-phase reactants that are usually present at high concentrations
      in the serum of patients with liver disease. However, the origin of these high
      serum concentrations is not completely understood, and whether hepatocellular
      carcinoma (HCC) tissue is a contributing factor is a controversial issue. The
      purpose of this study was to investigate the profiles of these three proteins in
      patients with HCC before and after tumor resection, and to study factors that
      might affect the serum concentrations of these proteins. A retrospective cohort
      study was performed in 34 consecutive patients who underwent HCC resection at the
      National Taiwan University Hospital. Blood samples were collected before surgery
      and on days 1, 3, 5, 7, and 14 postoperatively for serum concentration
      determinations of these three proteins. Twenty-three patients admitted for health
      examinations were enrolled as normal controls. Multiple regression analysis was
      conducted to evaluate the correlations between the pre- and postoperative
      cytokine concentrations and various clinical parameters. Compared with normal
      controls, the HCC patients had a significantly higher preoperative concentration
      of HGF (1,472 +/- 73 vs 948 +/- 54 ng/mL, p < 0.001) and IL-6 (44.1 +/- 6.9 vs
      8.1 +/- 3.2 pg/mL, p = 0.012). These concentrations peaked on the first
      postoperative day and then declined to preoperative values on the fifth
      postoperative day. The CRP concentration was also higher in HCC patients (0.88 +/
      0.22 vs 0.21 +/- 0.06 mg/dL, p = 0.222), but the difference was not
      statistically significant. However, the CRP concentration did not return to the
      preoperative value within 2 weeks postoperatively. Preoperatively, HGF and CRP
      concentrations were positively affected by larger tumor size, and IL-6
      concentration was negatively affected by hepatitis B surface antigen positivity
      and a higher indocyanine green (ICG) retention rate. In summary, the serum
      concentrations of HGF and IL-6 were significantly higher in HCC patients than in
      normal controls. The serum concentrations of HGF, IL-6, and CRP rose dramatically
      after HCC resection. The concentrations of these proteins were affected by
      different clinical parameters. We proved indirectly that high serum
      concentrations of HGF, IL-6, and CRP in patients with HCC do not result primarily
      from synthesis by the tumor cells. Whether the preoperative concentrations of
      these proteins correlate with the clinical outcome needs further follow-up.

PMID- 10083763
TI  - Tissue hepatocyte growth factor and proliferating cell nuclear antigen in
      hepatocellular carcinoma.
AB  - To better understand the roles of hepatocyte growth factor (HGF) and
      proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC), 37
      surgically resected HCCs and corresponding nontumorous liver tissue specimens
      were collected and the expression of these two factors was quantified by Western
      blot analysis. Both HGF and PCNA expression levels were significantly higher in
      tumor tissue than in nontumorous liver tissue. However, their expression levels
      in HCC tissue and nontumorous tissue did not show any significant correlation
      with the recurrence of HCC. In addition, HGF and PCNA did not correlate with
      Edmondson's grade, invasiveness of tumor, presence of tumor capsule, or tumor
      size. No correlation was found between the expression levels of HGF and PCNA in
      HCC tissue. We conclude that, although both HGF and PCNA are present at higher
      levels in HCC tissue than in nontumorous liver tissue, they play little role in
      the clinicopathologic manifestations of this tumor. HGF appears to contribute
      little, if at all, to the proliferative activity of HCC cells.

PMID- 10083764
TI  - Diagnostic efficacy of non-breath-hold magnetic resonance
      cholangiopancreatography.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is an emerging imaging
      technique for direct visualization of biliary and pancreatic ducts without the
      need for an invasive procedure, ionizing radiation, or iodine contrast media
      administration. The purpose of this study was to evaluate the efficacy of non
      breath-hold MRCP in depicting normal and diseased biliary and pancreatic ducts. A
      retrospective analysis of 162 patients who underwent MRCP was performed, and a
      comparison between MRCP and direct cholangiography was made. The overall accuracy
      of MRCP in diagnosing malignant and benign pancreaticobiliary diseases was also
      calculated. MRCP depicted more than three hepatic segments in 99% of patients
      with dilated intrahepatic ducts and in 63% of patients with nondilated
      intrahepatic ducts. MRCP demonstrated the main hepatic duct, gallbladder, and
      cystic duct in 100%, 89%, and 72% of patients, respectively. The dilated
      extrahepatic duct, nondilated extrahepatic duct, dilated pancreatic duct, and
      nondilated pancreatic duct were visualized in 100%, 98%, 95%, and 77% of
      patients, respectively. The accuracy of MRCP in diagnosing hepatolithiasis,
      cholecystolithiasis, and choledocholithiasis was 96%, 97%, and 96%, respectively.
      The obstruction levels and characteristics determined by MRCP were in agreement
      with those determined from direct cholangiography in 98% of malignant
      obstructions and 89% of benign obstructions. The overall accuracy of a
      combination of MRCP and conventional magnetic resonance imaging in diagnosing
      pancreaticobiliary diseases was 81% for malignant diseases, 86% for benign
      diseases, and 82% for stone diseases. We conclude that non-breath-hold MRCP can
      reliably depict normal and diseased pancreaticobiliary ducts except for cystic
      ducts and nondilated pancreatic ducts.

PMID- 10083765
TI  - Effects of lovastatin and gemfibrozil in subjects with high ratios of total
      cholesterol to high-density lipoprotein cholesterol.
AB  - Insulin resistance is associated with hypertriglyceridemia, low serum high
      density lipoprotein cholesterol (HDL-C) concentrations and high serum total
      cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either
      lovastatin or gemfibrozil may favorably lower serum lipid concentrations.
      However, their effects on insulin sensitivity are unknown. The primary aim of
      this study was to compare the effects of lovastatin and gemfibrozil on insulin
      sensitivity and serum leptin concentrations in subjects with high TC/HDL-C
      ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight
      with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with
      lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day.
      Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose
      tolerance test (OGTT) and a modified insulin suppression test were performed
      before and after 3 months of treatment. The study showed the mean plasma TC, low
      density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were
      significantly reduced in the lovastatin-treated group, but no obvious effects on
      plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma
      TG and HDL-C were markedly lowered, but no significantly different effects in
      other plasma lipids were found. Gemfibrozil did not affect steady-state plasma
      glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG
      concentrations. Neither drug affected the serum leptin concentration during the
      OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio,
      and TC/HDL-C concentrations and adversely affects insulin sensitivity, while
      gemfibrozil markedly reduces plasma TG concentrations without altering insulin
      sensitivity in subjects with high TC/HDL-C ratios.

PMID- 10083767
TI  - Renal cell carcinoma: unusual pediatric renal tumors.
AB  - Renal cell carcinoma (RCC), the most common renal tumor in adults, is rare in
      childhood, with an incidence much lower than that of Wilms' tumor. It is
      initially asymptomatic, but clinically overt symptoms such as an abdominal mass
      or hematuria may indicate late-stage disease and a poor prognosis. In this
      report, we describe the imaging features of pediatric RCC and emphasize the value
      of early diagnosis offered by ultrasonographic screening. From 1989 through 1997,
      we encountered five children (aged 7-15 yr) with RCC. Of these, two presented
      with symptoms, while the other three were asymptomatic and were identified in a
      large, school-based urologic ultrasonographic survey, in which more than 800,000
      children were screened by our team. Reviewing the imaging features, we found that
      four tumors exhibited a heterogeneous nature. One patient had bilateral well
      defined homogeneous tumors, which proved to be bilateral low-grade RCC. The three
      asymptomatic patients had smaller tumors than the other two patients. These three
      were treated with nephrectomy and were well after at least 15 months of follow
      up. The two patients who presented with symptoms eventually died of tumor
      recurrence and pulmonary metastasis, respectively. The findings in these five
      cases of pediatric RCC add knowledge regarding the imaging features of this
      disease and highlight the value of ultrasonographic screening for early
      diagnosis.

PMID- 10083766
TI  - Regulation of vascular endothelial growth factor secretion in human meningioma
      cells.
AB  - Previously, we induced vascular endothelial growth factor/vascular permeability
      factor (VEGF/VPF) secretion in glioma cell lines by using physiologic
      concentrations of epidermal growth factor (EGF), basic fibroblast growth factor
      (bFGF), or platelet-derived growth factor-BB (PDGF-BB). We hypothesized that
      VEGF/VPF might enhance the blood supply required for the unregulated growth of
      tumors, and that it acts as the central mediator of tumor angiogenesis. The
      objective of this study was to determine whether the expression of VEGF/VPF by
      meningiomas is regulated by growth factors or sex hormones. By means of an enzyme
      linked immunosorbent assay of CH-157MN meningioma cell supernatants, we
      demonstrated that EGF and bFGF similarly induce VEGF secretion by CH-157MN
      meningioma cells. At the maximum concentrations of EGF (50 ng/mL) and bFGF (50
      ng/mL) used in this study, VEGF secretion was induced to 140% to 160% above
      baseline constitutive secretion. PDGF-BB homodimer did not enhance VEGF secretion
      significantly. Estradiol (up to 10(-7) mol/L), progesterone (up to 10(-5) mol/L),
      or testosterone (up to 10(-5) mol/L) did not stimulate or inhibit VEGF secretion
      in CH-157MN meningioma cells (p > 0.05). Furthermore, we demonstrated that
      dexamethasone decreased VEGF secretion to 32% of baseline constitutive secretion.
      This might explain the effect of corticosteroids in alleviating peritumoral brain
      edema in meningiomas. These results suggest that VEGF secretion in CH-157MN
      meningioma cells is mainly regulated by growth factors and corticosteroids, but
      not by sex hormones. Understanding the regulation of VEGF/VPF secretion in
      meningiomas might contribute to the development of a new therapeutic strategy.

PMID- 10083768
TI  - Surgical treatment of recurrent groin hernia.
AB  - Recurrent groin hernia is not uncommon in Taiwan. Subsequent surgical repairs are
      difficult, due to cicartrization and deterioration of the inguinal floor. In this
      report, the intermediate and long-term outcomes of 212 patients with recurrent
      groin hernias who underwent surgical repair within a 10-year period were analyzed
      in order to assess the effectiveness of two modified repair techniques. Patients
      with unilateral first-time recurrent hernia (UR; n = 87) were treated by a
      modified Shouldice technique using an inguinal approach. Those with bilateral or
      multiple recurrences (MRs; n = 125) were treated with giant prosthetic
      reinforcement of the visceral sac (GPRVS, Stoppa operation) using a midline
      preperitoneal approach. Complete exploration of the groin floor on the side of
      recurrence revealed a high rate of direct space defects (UR, 41.5%; MR, 65%) and
      multiple posterior wall defects (UR, 29.9%; MR, 30%). In the UR group, a 4 x 10
      cm preperitoneal prosthetic mesh was incorporated to reinforce the repair. For MR
      patients, I reduced the transverse dimension of the mesh prosthesis by 2 cm
      compared with the original Stoppa protocol; to reduce crinkling, the average
      dimensions were 23 x 14 cm. Complications in the UR group included testicular
      atrophy (3 patients) and femoral vein thrombosis (1). Complications in the MR
      group were transient scrotal fluid accumulation (9 patients), fatal perioperative
      acute myocardial infarction (1), and failure of the peritoneum to grow over the
      mesh (1). The average hospital stay was 3 days in the UR group and 6 days in the
      MR group. The long-term follow-up (1-9 years) revealed a 5.7% re-recurrence rate
      with an 86.2% follow-up rate in the UR group, and a 1.9% re-recurrence rate with
      an 86.6% follow-up rate in the UR group. I conclude that GPRVS is an excellent
      treatment for URs, but the transverse dimension of the prosthetic mesh should be
      reduced for Taiwanese subjects. However, for first-time MRs, a modified Shouldice
      technique with incorporation of a preperitoneal prosthetic mesh is still
      recommended. The surgical dissection is less extensive and the hospital stay is
      shorter, while the re-recurrence rate is acceptably low.

PMID- 10083769
TI  - Clinical experience with endoscopic stents for treatment of common bile duct
      stones.
AB  - Endoscopic removal of common bile duct (CBD) stones after endoscopic
      sphincterotomy (EST) is now a widely accepted procedure. Surgery is usually
      recommended when extraction of stones after EST fails. For patients with major
      medical problems or who are at high surgical risk, however, endoscopic stent
      placement may help to prevent stone impaction and cholangitis. In this report, we
      describe the long-term effects and complications of biliary stent use in elderly
      patients with CBD stones. From August 1995 to June 1998, 19 patients with CBD
      stones underwent stent placement by duodenoscopy. Three of these patients
      underwent this procedure for temporary treatment while awaiting surgery or EST.
      In the remaining 16 patients (6 men and 10 women, mean age 76 +/- 10 years),
      invasive management carried a high risk of complications. We used a 7F straight
      stent for the first patient, while the remaining 15 received 7F pigtail stents.
      During a mean follow-up period of 34 months, two patients were lost to follow-up
      and two patients had migration of the stents. Three patients had acute
      cholangitis with stents in situ. Of these, one underwent stent exchange 8 months
      later, while the CBD stones were cleared either by endoscopy or surgery in the
      other two patients. Five patients died of nonbiliary diseases during the follow
      up period. Our results show that long-term biliary stent placement is an
      advisable alternative therapeutic modality for high-risk and debilitated patients
      with CBD stones.

PMID- 10083770
TI  - Endobronchial metastasis of glioblastoma multiforme diagnosed by fiberoptic
      bronchoscopic biopsy.
AB  - We report a case of extraneural metastasis of an intracranial glioblastoma
      multiforme (GBM) to the left upper lung, in which fiberoptic bronchoscopy played
      a key role in the diagnosis. The patient, a 20-year-old woman, presented with dry
      cough and hoarseness 2 years after total excision of the brain tumor and
      postoperative radiotherapy. Tissue samples obtained during fiberoptic
      bronchoscopic biopsy had the same morphologic appearance as the primary
      intracranial tumor, which was consistent with GBM. In cases of pulmonary
      metastasis of GBM, antemortem diagnosis is rare. Our experience from this case
      suggests that fiberoptic bronchoscopy may be a valuable diagnostic tool for
      metastatic GBM.

PMID- 10083771
TI  - Coronary dissection and myocardial infarction following blunt chest trauma.
AB  - Myocardial infarction (MI) following blunt chest trauma is rarely diagnosed
      because the ensuing cardiac pain is commonly attributed to contused myocardium or
      the traumatic injuries in the local chest wall. There are only scattered reports
      on the coronary pathology associated with MI secondary to blunt chest trauma.
      Because differentiation of the pathology is difficult but important, we report
      here three cases of acute anterior MI secondary to coronary dissection following
      blunt chest trauma. Coronary dissection was demonstrated by coronary angiography.
      Two of the patients had intimal tears at the proximal left anterior descending
      artery (LAD) with normal flow, and the other patient had nearly total occlusion
      of the LAD associated with filling defects probably caused by an intracoronary
      thrombus. All three patients received conservative treatment without major
      complications and remained free from angina or heart failure throughout a 5-year
      follow-up period. In order to exclude associated MI in cases of blunt chest
      trauma, electrocardiography is necessary, and coronary angiography may be
      indicated to demonstrate coronary arterial pathology. Dissection of the coronary
      artery with subsequent thrombus formation is one of the possible pathophysiologic
      mechanisms of MI following blunt chest trauma.

PMID- 10083772
TI  - Progressive outer retinal necrosis syndrome as an early manifestation of human
      immunodeficiency virus infection.
AB  - Progressive outer retinal necrosis syndrome is a recently recognized variant of
      necrotizing herpetic retinopathy, developing in patients with acquired immune
      deficiency syndrome (AIDS) or other conditions causing immune compromise. We
      report a case in which the diagnosis of retinal necrosis syndrome was made before
      the diagnosis of AIDS was confirmed. A 41-year-old man presented with a 1-month
      history of blurred vision in his left eye. Ophthalmologic examination revealed
      extensive retinal necrosis with total retinal detachment in his left eye and
      multifocal deep retinal lesions scattered in the posterior fundus as well as in
      the peripheral retina in his right eye. The serologic test for human
      immunodeficiency virus (HIV) was positive. Despite intravenous acyclovir
      treatment for 1 week, the lesions in the right eye showed rapid progression. High
      doses of intravitreal ganciclovir were then given in addition to intravenous
      acyclovir. After combined treatment for 1 month, the lesions became quiescent and
      the visual acuity improved to 20/30. Although the patient soon developed full
      blown AIDS, the vision in his right eye remained undisturbed. Physicians should
      suspect progressive outer retinal necrosis syndrome in any patient with rapidly
      progressive necrotizing retinopathy and test the patient for HIV infection.
      Aggressive combined antiviral agent therapy should be considered to save vision.

PMID- 10083773
TI  - Hepatic abscess due to gastric perforation by ingested fish bone demonstrated by
      computed tomography.
AB  - Perforation of the gastrointestinal tract by ingested foreign bodies is rare.
      Preoperative diagnosis of complications due to foreign bodies in the
      gastrointestinal tract can rarely be achieved because the conventional
      radiographic appearance is nonspecific. This report describes a 69-year-old woman
      who presented with vague clinical manifestations, intermittent abdominal pain,
      and low-grade fever. Hepatic abscess, secondary to a foreign body penetrating the
      gastric wall, was diagnosed preoperatively using computed tomography findings. On
      exploration, the foreign body turned out to be a fish bone. The abscess was
      confirmed and drained during surgery and a partial gastrectomy was performed.
      This case illustrates the value of CT in the evaluation of this condition.

PMID- 10083774
TI  - The Cuban Health-Care System: a study on universal health care.

PMID- 10083775
TI  - The disability-poverty connection in older people.

PMID- 10083776
TI  - A critical approach to stress-related disorders in African Americans.
AB  - This article outlines an integrative, dynamic approach to stress and is, in part,
      a response to emergent debates within social science research and practice that
      suggest that African Americans are currently experiencing the reverberating
      psychological effects of slavery and oppression. It is the product of the work of
      an African-American mental health think tank situated at the Community Mental
      Health Council, Chicago, Illinois. We suggest the need to attend to
      biopsychosocial, environmental, and cultural factors that inform both exposure
      and responses to stress. Finally, consideration is given to matters of
      resiliency.

PMID- 10083777
TI  - Influence of maternal ethnicity on infant mortality in Chicago, 1989-1996.
AB  - This study compared infant mortality rates between large ethnic groups in Chicago
      from 1989-1996. Infant mortality information about ethnic groups was compared
      using data from annual reports published by the Epidemiology Program, Department
      of Public Health, City of Chicago and vital statistics documents in Illinois,
      which include information on ethnicity. Chi-squared analysis was used to evaluate
      the differences between the proportions. A P value of < .05 was considered
      significant. During the study period, there were 461,974 births and 6407 infant
      deaths in Chicago. African Americans contributed 212,924 (46.1%) births and 4387
      (68.5%) deaths; Hispanics 132,787 (28.7%) births and 1166 (18.2%) deaths; and
      whites 99,532 (21.6%) births and 780 (12.2%) infant deaths. Compared with the
      other groups. African Americans suffered a twofold increased mortality (P <
      .00001) for five of the six most common causes of infant mortality. Deaths from
      congenital malformations, although significant, were not excessively increased
      among African Americans (P = .014). Hispanics demonstrated a higher mortality
      rate than whites (P = .01), especially for postnatal mortality and respiratory
      distress syndrome. These data confirm excessive infant mortality among African
      Americans. Further studies are needed to evaluate the apparent low mortality
      among some Hispanics compared with the other groups studied.

PMID- 10083778
TI  - HIV risk differences between African-American and white men who have sex with
      men.
AB  - African-American men who have sex with men remain at disproportionately greater
      risk for contracting human immunodeficiency virus (HIV) infection. While high HIV
      seroincidence has been documented among homosexual African-American men,
      behavioral research has rarely studied the HIV risk issues confronting these men.
      This study assessed a sample of 253 men who have sex with men to determine if
      African-American (n = 79) and white (n = 174) men report different rates of HIV
      risk behaviors and differ in characteristics indicative of risk. African-American
      men who have sex with men were more likely to be HIV-seropositive, to report past
      treatment for gonorrhea and syphilis, and to have a recent unprotected sex
      partner known or believed to be HIV-seropositive. Multivariate analyses of
      covariance, controlling for group differences in age, education, and income,
      revealed that African-American men who have sex with men were less open about
      their sexual orientation, scored lower in HIV risk behavior knowledge, had more
      female sexual partners, and more frequently used cocaine in association with sex
      relative to white men who have sex with men. Human immunodeficiency virus
      prevention programs tailored to the needs and risk issues of African-American men
      who have sex with men are needed.

PMID- 10083779
TI  - African Americans in ophthalmology.

PMID- 10083780
TI  - The power of words.

PMID- 10083781
TI  - Should parents participate in patient rounds in the NICU?

PMID- 10083782
TI  - Acute renal failure in pregnancy.
AB  - Acute renal failure (ARF) during pregnancy is a rare event. However, the care of
      the woman diagnosed with ARF is a challenge for the perinatal care team. The
      physiologic hydronephrosis and hydroureter of pregnancy alters clinical
      parameters for assessing the woman diagnosed with ARF. Urinary stasis and
      enhanced filtration predisposes to alterations in 24-hour urine evaluations,
      increased urinary creatinine excretion, and lower BUN and serum creatinine
      values. If the renal system becomes compromised, the woman is at risk for
      acidemia, fluid and electrolyte imbalances, and pregnancy compromise. The
      perinatal nurse must have an understanding of normal pregnancy physiology and an
      appreciation for how pregnancy physiology may alter renal assessments.
      Furthermore, the nurse must know the impact that ARF can have on maternal status
      and fetal well-being. Astute, continuous assessments of maternal and fetal status
      are required to detect subtle changes. While maternal status is the primary
      concern, it must not be forgotten that a change in fetal status may be the first
      indication of underlying maternal compromise.

PMID- 10083783
TI  - Maternal kangaroo (skin-to-skin) care in the NICU beginning 4 hours postbirth.
AB  - Kangaroo care (KC) for preterm infants is becoming well known in the United
      States. Typically, KC is given by mothers in the neonatal intensive care unit
      (NICU) beginning days or weeks postbirth. This case report documents KC beginning
      at 4.5 hours postbirth with a healthy mother whose 32-week, 1,953 gram infant
      required initial care in the NICU. The nurse's role in supporting this care is
      described. Both parents experienced KC with their son and were soon convinced of
      the exceptional benefits he received. The infant was transferred to intermediate
      care on Day 2, regained his birth weight by Day 12, was discharged home on Day
      21. He was breast-feeding exclusively at 40 weeks corrected age, and had Bayley
      mental and motor development scores within normal limits at 6 months corrected
      age.

PMID- 10083784
TI  - Biochemical markers for preterm labor and birth: what is their role in the care
      of pregnant women?
AB  - Two biochemical tests, one for oncofetal fibronectin (fFN) and the other for
      estriol found in maternal saliva (SalEst) have been developed to improve the
      ability to predict preterm labor and birth. Fetal fibronectin is a protein
      secreted by the trophoblast and not normally present in vaginal and cervical
      secretions late in pregnancy. The presence of fFN between 22 and 37 weeks
      gestation may be a marker for preterm labor. Salivary estriol is a form of
      estrogen produced in the placenta from fetal precursors. Normally, estriol rises
      during pregnancy--the rise being accelerated 3 to 5 weeks prior to both term and
      preterm births. Both tests have high negative predictive values. This may serve
      to prevent unnecessary treatment of women with uterine contractions who are not
      truly in preterm labor. The fFN specimen is collected during vaginal examination.
      Sexual intercourse or vaginal examination within the prior 24 hours, vaginal
      bleeding, and uterine contractions may lead to a false positive test. Salivary
      estriol may be collected by the woman in her own home; however, specific
      instructions about eating, drinking, smoking, and the timing of saliva collection
      must be followed. Further study of both tests is required to determine their
      potential for reducing rates of preterm birth.

PMID- 10083785
TI  - Prevention: are we really reaching today's teens?
AB  - Adolescence is the time when health risks can stem from lifestyle choices.
      According to the Centers for Disease Control and Prevention (CDC), only a few
      behaviors account for most of the mortality, morbidity, and social problems in
      adolescents. These behaviors are: behaviors that result in unintentional or
      intentional injuries; drug and alcohol use; sexual behavior; diet; tobacco use;
      and physical inactivity. This article provides nurses with baseline prevention
      strategies to use with adolescents, parents, and communities, as well as
      suggestions for minimizing the incidences of preventible health problems.

PMID- 10083786
TI  - Fantasies of the unborn among pregnant women.
AB  - PURPOSE: This investigation sought to describe how pregnant women fantasize about
      their unborn children. METHODS: A questionnaire using one open-ended question was
      given to 210 pregnant women in childbirth education classes. The final sample was
      184. Content and matrix analyses were used to identify evidence of fantasy
      patterns in primiparas and multiparas, as well as patterns among the three
      gestational trimesters. RESULTS: Results indicate that fantasies have a
      developmental component across gestational trimesters and differ between
      multiparas and primigravidas. Ten major themes were derived. IMPLICATIONS:
      Routine assessments of prenatal fantasy might help to promote healthy behaviors
      in pregnant women and enhance positive interpersonal relationships between the
      provider and client. Future research is needed to discern the impact of antenatal
      fantasies on maternal role development.

PMID- 10083787
TI  - Assessment of stressors in families with a child who has a chronic condition.
AB  - Nurses working with families who have children with a chronic condition are aware
      of the complexity of the tasks and stresses they deal with daily. The challenge
      is to uncover the issues that require the most immediate intervention while
      noting others for the future. This article describes the development of a
      comprehensive guide for experienced nurses to identify a family's stressors and
      tasks. It can be used with a broad range of chronic diagnoses. Nurses who have
      used the guide report that it helped them to focus and plan timely, appropriate
      nursing interventions with these families. It also serves as a record and
      planning tool for documenting issues that may become priorities for future
      interventions.

PMID- 10083788
TI  - Tamoxifen in the news ... again!

PMID- 10083789
TI  - Non-insulin dependent diabetes in India: a forgotten epidemic.

PMID- 10083790
TI  - Severe weight loss: the predominant clinical presentation of tuberculosis in
      patients with HIV infection in India.
AB  - BACKGROUND: Tuberculosis is endemic in India and its prevalence is reported to be
      increasing in patients with human immuno-deficiency virus (HIV) infection.
      Several factors, including the level of immune deficiency, influence the clinical
      presentation of HIV-associated tuberculosis. METHODS: Between April 1994 and
      April 1996, 1820 patients with confirmed HIV infection were studied for their
      clinical, radiological and laboratory parameters. Severe weight loss was observed
      as a frequent presenting complaint. Hence, a case-control analysis was performed
      using severe weight loss as the presenting criterion among HIV-seropositive
      patients. RESULTS: Of the 1820 patients with HIV infection, 410 (23%) presented
      with severe weight loss of > 10% of body weight within the preceding month. Of
      these 410 patients, 176 (43%) had tuberculosis, 94 (23%) had chronic diarrhoea,
      and 89 (22%) had recurrent fever. Among 176 patients with tuberculosis, the
      following types of HIV-associated tuberculosis were seen: 115/176 (66%) had
      pulmonary, 49/176 (28%) had extrapulmonary tuberculosis; of these 49 cases with
      extrapulmonary tuberculosis 33 (18%) had disseminated tuberculosis, and 12/176
      (7%) had both pulmonary and extrapulmonary involvement. In the group as a whole,
      45/176 (25%) cases had disseminated tuberculosis. Clinical features of HIV
      associated tuberculosis in decreasing order of frequency were chronic fever,
      chronic cough, lymphadenopathy and hepatosplenomegaly. The Mantoux skin test was
      significantly anergic among patients with extrapulmonary and disseminated
      tuberculosis (p = 0.001). CONCLUSIONS: There was a significant correlation
      between severe weight loss and tuberculosis (RR 17.5), chronic diarrhoea (RR
      12.8) and recurrent fever (RR 4.5). The diagnostic value of the Mantoux skin test
      among HIV-associated tuberculosis is reduced, more so among those with
      extrapulmonary and disseminated forms.

PMID- 10083791
TI  - Detection of chromosomal abnormalities using fluorescence in situ hybridization
      (FISH).
AB  - BACKGROUND: A number of studies have demonstrated the use of molecular
      cytogenetic techniques for clinical diagnosis. We compared the results of FISH
      analysis and conventional cytogenetics on different tissue samples for detection
      of chromosomal aberrations and to assess the utility of FISH assay for clinical
      diagnosis. METHODS: Karyotypic analysis was carried out on 50 samples--20
      peripheral blood samples, 20 bone marrow samples and 10 prenatal (chorionic
      villi/amniotic fluid) samples. The same chromosome preparations were further
      subjected to FISH analysis using probes specific for chromosome X, Y, 21 or bcr
      abl gene. RESULTS: The results of FISH analysis were in conformity with the
      cytogenetic results in all the samples except one. FISH analysis could reveal
      hybridization signals even on poorly spread metaphase chromosomes and interphase
      nuclei. It was also possible to detect subtle chromosomal aberrations which were
      not detected using conventional chromosomal analysis. CONCLUSION: FISH is a
      powerful, sensitive molecular cytogenetic technique which can be used as an
      adjunct to conventional chromosomal analysis for prenatal diagnosis and the
      diagnosis and management of cancer patients. FISH analysis should be used as a
      supplement to conventional cytogenetics.

PMID- 10083792
TI  - Snake bites in the hills of north India.
AB  - BACKGROUND: Snake bites are a common cause of morbidity and mortality in the
      hills. The risk of snake bite is high due to the presence of a huge herpeto fauna
      flourishing in a favourable climate--low environmental temperature and heavy
      rainfall. In India, there are 236 species of snakes of which four are dangerously
      venomous. This study was undertaken to determine the risk factors exposing the
      population to snake bite and the common types of snakes causing them. METHODS: We
      studied 243 patients of snake bite over a period of 24 months. All patients were
      examined for evidence of snake bite and, where possible, the snakes were
      identified based on description, identification (if the snake was brought) and
      symptoms of envenomation. RESULTS: Seasonal variation in snake bite was seen,
      with a peak in the months of August and September. No bites were recorded in
      December, January and February. Eighty-four per cent of the bites were on the
      hands and feet (up to the ankle). Bites on the hand were more common in females
      with a left hand preponderance (3.5 times higher). The age group most affected
      was between 11 and 40 years (73.7%). Most bites occurred while the person was
      cutting grass, working in the fields or walking in the hills (75.3%). Snake bites
      while sleeping were at uncommon sites. Non-poisonous snakes were the most common
      (90.5%). Kraits caused 60% of bites with envenomation. CONCLUSION: Snake bites
      occur frequently in the hills of Himachal Pradesh. Although snake bites are a
      cause for concern, most of them are caused by non-poisonous snakes.

PMID- 10083793
TI  - Changing pattern of antibiotic sensitivity of Salmonella typhi.
AB  - BACKGROUND: The emergence of multidrug-resistant Salmonella typhi led to the use
      of quinolones as the first-line drug in the treatment of adult patients with
      typhoid fever. However, over the last few years there has been an impression that
      patients on ciprofloxacin tended to take longer to defervesce. We studied the
      response and antibiotic sensitivity patterns during 2 time periods to assess the
      changes that may have occurred. METHODS: A retrospective analysis was done of
      blood culture-positive patients with Salmonella typhi infection during 1991 and
      1996-97. The mode of presentation treatment history, antibiotic sensitivity
      pattern, antibiotics administered, response to therapy and the complications that
      ensued were studied. RESULTS: In vitro sensitivity to ciprofloxacin was found to
      be 100% in both the study groups. It was found that a greater number of patients
      were sensitive to ampicillin (80%), chloramphenicol (80%) and co-trimoxazole
      (80%) during 1996-97 as compared to 1991, when sensitivity to ampicillin was 63%,
      chloramphenicol 65% and co-trimoxazole 65%. The mean (SD) defervescence period in
      1991 was 6 (2.3) days and in 1996-97 was 6 (2) days (p > 0.05). CONCLUSION: In
      vitro sensitivity of Salmonella typhi to ciprofloxacin remains 100%. There was an
      increase in the sensitivity to ampicillin, chloramphenicol and co-trimoxazole
      which have been rarely used over the past few years. There was no significant
      difference in the time taken to defervesce between the two study periods.

PMID- 10083794
TI  - Quantitative food frequency questionnaire and assessment of dietary intake.
AB  - India is a land of varied foods and food habits. This makes the task of
      collecting dietary and nutrient intake data difficult. Methods need to be devised
      to improve the accuracy in reporting intakes by various population subgroups.
      There is an urgent need to develop a questionnaire that is simple enough to be
      administered on a large sample and whose validity and reproducibility has been
      quantified. Regional differences in food habits and availability will have to be
      taken into account in the questionnaire design. Packaging of food items with
      definite portion sizes is not a common practice in Indian markets and labels on
      food products are neither very informative nor descriptive. Epidemiologists
      addressing the effects of diet have generally used questionnaires that inquire
      about the frequency of specified foods consumed and sometimes also attempt to
      quantify usual portion sizes. A number of investigators have conveyed, apparently
      independently, that the food frequency questionnaire (FFQ) as a method of dietary
      assessment is best suited for most epidemiological applications. A food frequency
      list can form the basis for nutrition education and allows the dietician and the
      patient to relate individual eating patterns to specific foods. Other advantages
      of the FFQ are that it is independent of the ability or inclination of an
      individual to maintain a diary and also provides immediate feedback to patients,
      physicians and counsellors.

PMID- 10083795
TI  - Antituberculosis drug resistance: a global threat.

PMID- 10083796
TI  - A modern application for an ancient remedy.

PMID- 10083797
TI  - Constipation.
AB  - Constipation is a common problem in day-to-day practice. As there are wide
      variations in normal bowel habits, there is no standard definition. Altered
      colonic transit and disorders of the anorectal mechanism are the essential
      abnormalities in patients who experience this symptom. While there are several
      organic causes, functional disorders are by far the commonest cause of
      constipation. Clinical assessment should include a careful history, eliciting
      information on lifestyle, diet and personality. Extensive investigations are
      seldom warranted. Reassurance and long term treatment with a wide range of
      laxatives provide symptomatic relief.

PMID- 10083798
TI  - A step towards quality medical research.
AB  - Only well planned and conducted research can answer questions that arise in day
      to-day clinical practice. Unfortunately, most studies in India are deficient in
      design or execution. The results thus obtained are biased and cannot be
      extrapolated to the population studied. Some important questions which arise
      during the statistical design of investigations are selection of subjects on
      which observations are to be made, number of observations falling into different
      groups, allocation of subjects among different groups, etc. Besides planning and
      execution, appropriate methods need to be chosen for data analysis beforehand. If
      the study has been well designed and correctly analysed, the interpretation of
      results can be fairly simple. The present communication focuses on some issues
      relating to the planning of investigations in medical research with emphasis on
      statistical design.

PMID- 10083799
TI  - Psychiatric education for medical students.

PMID- 10083800
TI  - A virus questions human definitions of health.

PMID- 10083801
TI  - Hips and tips--new terminology in the National Health Service.

PMID- 10083802
TI  - Competency testing is now required for international medical graduates to enter
      residency programmes.

PMID- 10083803
TI  - Organizing a public debate: ethical guidelines on biomedical research in humans.

PMID- 10083804
TI  - Oral submucous fibrosis, areca nut and pan masala use: a case-control study.

PMID- 10083805
TI  - Medical education and health needs of a community.

PMID- 10083806
TI  - The medical examination system.

PMID- 10083807
TI  - Seasonal recurrent mania following head injury.

PMID- 10083808
TI  - Development of knowledge-based therapy for cancer: identification of unique
      targets.

PMID- 10083809
TI  - Competence in English and academic performance.

PMID- 10083810
TI  - Indian medicine and the Nobel prizes.

PMID- 10083811
TI  - [Selective inhibition of cyclooxygense (COX-2)].
AB  - The author gives a brood outline of the circumstances of the inhibition of
      cyclooxygenase (COX) giving special emphasis to the different role of the two
      isoforms COX-1 and COX-2. More selective COX-2 inhibition can be have required
      practical effect in reducing of inflammation with less side effects. To set a
      correct determination of COX-2/COX-1 quotiens is difficult because of numerous
      methodical problems. We have to rely on the clinical experiences gained through
      long usage of some drugs.

PMID- 10083812
TI  - [Viable myocardium revealed by contrast echocardiography].
AB  - In patients with acute ischemic syndrome left ventricular dysfunction may
      indicate necrotic myocardium as well as viable tissue. Among the well known non
      invasive techniques like dobutamine echocardiography, rest-redistribution
      thallium scintigraphy or positron emission tomography a new method, contrast
      echocardiography is evolving. In the presented case stunning resulting in left
      ventricular aneurysm formation was confirmed after intravenous injection of
      contrast agent and the use of intermittent harmonic imaging in the acute phase of
      ischemia. The negative coronary angiography and the complete restoration of the
      left ventricular function confirmed the results of contrast echocardiography.
      With the development of new second generation contrast agents and new techniques
      contrast echocardiography will become a feasible method for detection of viable
      myocardium after intravenous injection.

PMID- 10083813
TI  - [Virologic aspects of juvenile laryngeal papillomatosis].
AB  - Juvenile laryngeal papillomatosis is the most common benign tumor of the larynx
      in childhood. The specific etiological factors are non-oncogenic human
      papillomavirus types 6 and 11. In the present study two cases (a 6-year-old male
      and a 5 and a half-year-old female) operated five times each and harbouring type
      11 DNA in papillomas excised in the first operations are analysed from the
      following virological aspects: 1. the examination of vertical transmission by
      general primer-polymerase chain reaction of maternal cervical exfoliation; 2.
      sites of papilloma predilections in the larynx; 3. histopathology; 4. viral DNA
      detection from the formalin-fixed and paraffin-embedded archive tissues and from
      a fresh papilloma tissue in one case by polymerase chain reaction applying type
      specific primers. We did not find any signs of maternofoetal transmission in the
      anamnesis and the maternal cervix proved to be negative for viral DNA. However,
      the vertical route of transmission can not be excluded due to the special natural
      history of papillomavirus infections. Papillomas usually localised in normal
      squamociliary junctions of the larynx. The histopathologic review did not reveal
      any signs of malignancy. Koilocytosis referring to productive viral infection and
      the signs of abnormal keratinisation were present in each tissue. All tissues of
      the patients proved to be positive for the short amplimer deriving from the
      genome of human papillomavirus type 11.

PMID- 10083814
TI  - [Diagnostic value of serum erythropoietin levels].
AB  - Erythropoietin (Epo) is a hormone-like glycoprotein regulating erythropoiesis.
      Under normal conditions Epo stimulates mitoses of the erythroid progenitors and
      precursors, decreases apoptosis, decreases "ineffective erythropoiesis" and
      stimulates the synthesis of the specific protein, haemoglobin. Epo producing
      cells in the kidney sense the O2 tension of kidney tissue and react to hypoxia
      with increased Epo production and to O2 saturation (polycythaemia) with decreased
      or completely abolished Epo production. Normal level of Epo in the serum is 3-20
      mU/ml. If Epo production is functioning normally there exists a strict inverse
      correlation between serum Epo level and hematocrit: an exponential increase in
      Epo level can be observed if hematocrit decreases. Any damage in Epo production
      lead to inadequate production (e.g. renal anaemias). This paper analyses the Epo
      content of 278 serum samples assayed in the Laboratory of Experimental Bone
      Marrow Transplantation of the National Institute of Hematology and Immunology
      between August 1996 and December 1997 for their diagnostic value. Those samples
      are primarily discussed where Epo assay was meant to decide diagnosis of
      polycythaemia vera or those where decision of Epo treatment of anaemic patients
      depended on their serum Epo level.

PMID- 10083815
TI  - ["Morbus Hungaricus"--"Hungarian Disease". A chapter from the 16th century
      history of exanthematous typhus].

PMID- 10083816
TI  - [The forerunner of reflex therapy: Georg Prochaska (1749-1820)].

PMID- 10083817
TI  - [Prostatic cancer--a disease with a new profile].

PMID- 10083818
TI  - [Erectile dysfunction. An update].
AB  - Although around 10% of men aged 40 to 70 years have complete erectile
      dysfunction, only a few seek medical help. As erectile dysfunction is frequently
      associated with a number of systemic illnesses and surgical treatments, a wide
      range of doctors should be aware of the condition in their patients. Current
      effective treatments include psychosexual counselling, vacuum erection devices,
      intracavernosal and transurethral drug delivery, and penile prostheses. Promising
      oral treatments are currently being investigated. Both doctors and the public
      need to be better informed about erectile dysfunction and its treatment.

PMID- 10083819
TI  - [Development of post-traumatic stress following severe work-related accidents].
AB  - The diagnostic criteria for posttraumatic stress disorder (PTSD) employed by the
      American DSM-IV from 1994 and ICD-10 from 1993 are reviewed. The literature
      concerning PTSD, with particular focus on PTSD in relation to occupational
      accidents, is discussed. A single epidemiological study of the occurrence of PTSD
      following serious nonfatal occupational accidents reports a one to two years
      prevalence of PTSD of 4.3%. Physicians and safety and health organisations within
      companies should be aware of the potential for the occurrence of acute and
      chronic stress conditions following occupational accidents, primarily with
      respect to providing supportive psychological treatment and social support aimed
      at preventing the development of chronic symptoms.

PMID- 10083820
TI  - [Post-traumatic stress after occupational accidents].
AB  - This study focuses on post-traumatic stress disorder in a follow up one to two
      years after the occupational accident. The aim was to estimate the prevalence of
      PTSD, changes in general health status and issues of compensation. The material
      was all serious accidents registered in the Danish National Register of Work
      Accidents during 1991. Seriousness was defined by type of injury, including all
      cases of amputations, bone fractures and extensive body lesions. Of 4745
      possible, 3663 persons (77%) participated in a questionnaire study. The
      prevalence fulfilling the complete set of criteria of posttraumatic stress
      disorder as a chronic state was 2.8% (102 persons), of whom half had been given
      compensation. Among the most severe accidents the prevalence was 7.6%. In
      conclusion, in a large cohort of persons with moderate and severe occupational
      injuries this study demonstrated that post-traumatic stress disorder and lasting
      psychological distress should be a matter for concern in addition to the physical
      injury.

PMID- 10083821
TI  - [Laparoscopic ileocecal resection in Crohn disease].
AB  - Laparoscopic intestinal surgery has theoretical advantages compared with
      conventional intestinal surgery by minimizing the surgical trauma. The aim of the
      study was to examine the operative and postoperative course as well as the time
      for recovery after laparoscopic-assisted ileocoecal resection for Crohn's
      disease. Seventeen patients were operated on. The operations were assessed with
      regard to duration of operation, rate of conversion to open procedure,
      complications, time for discharge from hospital, and ability to take up work.
      Median operation time was 145 min. Two operations (12%) were converted to open
      procedure. Complications occurred in three patients (18%). Median postoperative
      time to discharge was five days. Median time to return to work was 26 days. In
      conclusion laparoscopic-assisted ileocoecal resection seems suited to Crohn's
      disease, but the benefit of the method needs confirmation in controlled,
      randomized studies.

PMID- 10083822
TI  - [Smoking and life expectancy among Danish men and women].
AB  - Studies reporting increased mortality in smokers are abundant, but only few have
      included large numbers of heavily smoking women. Based on three large Danish
      population studies we calculated median survival in smokers and never-smokers and
      compared the impact of smoking in men and women. Seventeen thousand six hundred
      and sixty-nine men and 13,525 women were followed for up to 30 years for all
      cause mortality. During follow-up there were 8644 deaths. Large differences in
      tobacco-exposure between men and women were found, in particular in older birth
      cohorts. Despite a smaller accumulated exposure, the impact smoking had on median
      survival was similar in men and women. Female inhaling heavy smokers (> or = 15
      cig./day) lost 9.4 and inhaling light smokers 7.4 years in comparison with female
      never-smokers. Corresponding loss of life-expectancy in males was 9.2 years and
      6.0 years, respectively. In conclusion, this study shows survival prospects in
      relation to smoking in both men and women in a way that is easily communicated.
      The results indicate that women who smoke as much as men run a relatively higher
      risk in terms of reduced life expectancy.

PMID- 10083823
TI  - [Investigation and treatment of solitary thyroid gland nodules by Danish
      endocrinologists. A questionnaire study].
AB  - In order to evaluate the attitude among Danish specialists in endocrinology
      towards the management of the solitary thyroid nodule a questionnaire study,
      based on a case report of a 42-year old woman with a solitary 2 x 3 cm thyroid
      nodule and absence of clinical suspicion of malignancy, was performed. Routine in
      vitro tests included serum TSH in all and FT4 and total T4 in more than half of
      the respondents. 99mTc scintigraphy and ultrasonography (US) were included by
      nearly 100% of the clinicians and additional fine-needle aspiration (FNA) was
      suggested by 90%. Regardless of a benign cytology, surgery was preferred by 66%
      and follow-up by the most of the remaining, while L-T4 therapy was suggested by
      only 2%. In case of clinical suspicion cytology was disregarded by most and
      surgery was preferred by 90% of the clinicians. The survey illustrates that both
      scintigraphy and US as well as FNA are used routinely, and that surgery is
      regarded as first choice of treatment by most Danish clinicians.

PMID- 10083824
TI  - [MMR-vaccination of children allergic to eggs].
AB  - To re-evaluate the recommendations for MMR-vaccination of children known to be
      allergic to eggs a descriptive study was carried out in which all reported
      allergic side effects for 1987-1996 were studied. During the 10 year period
      1,200,000 MMR vaccinations were given. Eighteen were found with immediate type
      hypertensity, but only eight presented symptoms within 24 hours. One child with
      egg-allergy reacted within 15 min presenting rhinitis and respiratory difficulty.
      None had anaphylactic shock. It was concluded that MMR vaccine may be
      administered to children allergic to eggs when given in a paediatric ward where
      appropriate emergency treatment is available.

PMID- 10083825
TI  - [Dopa-responsive dystonia of childhood].
AB  - A case story of dopa-responsive childhood dystonia is presented. The symptoms,
      diagnostics, pitfalls and treatment are discussed.

PMID- 10083826
TI  - [Post-traumatic stress disorder following an occupational accident].
AB  - Two cases of occupational accidents and post-traumatic stress disorder (PTSD) of
      various types are described. These accidents occurred in different occupations
      and encompass dramatic, life-threatening situations. The cases were compatible
      with a diagnosis of chronic PTSD. In both cases compensation for occupational
      injury was awarded on the basis of a PTSD diagnosis.

PMID- 10083827
TI  - [Extramammary Paget's disease interpreted as psoriasis].
AB  - We describe a case of extramammary Paget's disease (EMPD) in the lateral part of
      the breast of a woman with known psoriasis. The eczema was treated as psoriasis
      for three years. There were no macroscopic changes of the nipple or areola.
      Nodular swellings beneath the eczema proved to be infiltrating ductal carcinoma.
      The eczema showed the pattern of EMPD. A mastectomy was performed. Two foci of
      ductal carcinoma in situ were found in the mammary body and two foci of Paget's
      disease were found in the areola and nipple. Fourteen axillary lymph nodes were
      examined without signs of malignancy.

PMID- 10083828
TI  - [Respiratory tract infections as cause of acute myocardial infarction].

PMID- 10083829
TI  - [An open letter to the Scientific Research Committee].

PMID- 10083830
TI  - [Information to health personnel on increased examination of inborn metabolic
      errors in newborn infants].

PMID- 10083831
TI  - [Firing the editor of JAMA].

PMID- 10083832
TI  - [Ignorance does not hurt--or does it?].

PMID- 10083833
TI  - [Estrogen and breast cancer].

PMID- 10083834
TI  - [Misinformation about genetic tests].

PMID- 10083835
TI  - The impact of growing-season length variability on carbon assimilation and
      evapotranspiration over 88 years in the eastern US deciduous forest
AB  - Recent research suggests that increases in growing-season length (GSL) in mid
      northern latitudes may be partially responsible for increased forest growth and
      carbon sequestration. We used the BIOME-BGC ecosystem model to investigate the
      impacts of including a dynamically regulated GSL on simulated carbon and water
      balance over a historical 88-year record (1900-1987) for 12 sites in the eastern
      USA deciduous broadleaf forest. For individual sites, the predicted GSL regularly
      varied by more than 15 days. When grouped into three climatic zones, GSL
      variability was still large and rapid. There is a recent trend in colder,
      northern sites toward a longer GSL, but not in moderate and warm climates. The
      results show that, for all sites, prediction of a long GSL versus using the mean
      GSL increased net ecosystem production (NEP), gross primary production (GPP), and
      evapotranspiration (ET); conversely a short GSL is predicted to decrease these
      parameters. On an absolute basis, differences in GPP between the dynamic and mean
      GSL simulations were larger than the differences in NEP. As a percentage
      difference, though, NEP was much more sensitive to changes in GSL than were
      either GPP or ET. On average, a 1-day change in GSL changed NEP by 1.6%, GPP by
      0.5%, and ET by 0.2%. Predictions of NEP and GPP in cold climates were more
      sensitive to changes in GSL than were predictions in warm climates. ET was not
      similarly sensitive. First, our results strongly agree with field measurements
      showing a high correlation between NEP and dates of spring growth, and second
      they suggest that persistent increases in GSL may lead to long-term increases in
      carbon storage.

PMID- 10083836
TI  - Biological activity of the labdane diterpenes.
AB  - Biological activity of diterpenes of the labdane skeleton, isolated from the
      terrestrial plants and marine sources during the last ten years has been
      reviewed.

PMID- 10083837
TI  - Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum,
      selectively inhibits the activity of casein kinase II as a competitive inhibitor.
AB  - Ser/Thr protein kinases play important roles in signal transduction pathways that
      control the proliferation and differentiation of eukaryotic cells. In this paper,
      we present evidence that emodin, an anthraquinone derivative, selectively
      inhibits casein kinase II (CKII), a Ser/Thr kinase, as a competitive inhibitor.
      The results with ethyl acetate extracts of the rhizomes of Rheum palmatum showed
      that emodin significantly inhibited the activity of cyclin B/cdc2 protein kinase
      (cdc2). We measured IC50 values for emodin on the activities of several Ser/Thr
      protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C
      (PKC), cdc2, casein kinases I (CKI) and CKII. Interestingly, emodin inhibited
      CKII activity with an IC50 value of 2 microM, which was two to three orders of
      magnitude lower than those against the other kinases. Enzyme kinetic assays
      showed that emodin inhibited CKII activity as a competitive inhibitor against ATP
      with a Ki value of 7.2 microM. Collectively, we suggest that emodin is a
      selective CKII inhibitor, whose action mechanism is mediated through
      competitively binding to the ATP binding site.

PMID- 10083838
TI  - Selective inhibition of eukaryote protein kinases by anti-inflammatory
      triterpenoids.
AB  - The ursane triterpenoid alpha-amyrin and the lupane triterpenoid lupeol are
      potent inhibitors of the catalytic subunit (cAK) of rat liver cyclic AMP
      dependent protein kinase (PKA) with IC50 values of 8 and 5 microM, respectively.
      The palmitate and linoleate esters of alpha-amyrin and lupeol are also potent
      inhibitors of cAK (IC50 values in the range of 4-9 microM). alpha-Amyrin, lupeol
      and lupeol linoleate are much less potent as inhibitors of rat brain Ca(2+)- and
      phospholipid-dependent protein kinase (PKC) (IC50 values 32, 82 and 35 microM;
      respectively) and alpha-amyrin linoleate and the palmitate esters of lupeol and
      alpha-amyrin are ineffective or very poor inhibitors of this protein kinase.
      These compounds are very poor or ineffective as inhibitors of chicken gizzard
      calmodulin-dependent myosin light chain kinase (MLCK). alpha-Amyrin inhibits
      plant Ca(2+)-dependent protein kinase (CDPK) (IC50 52 microM) but lupeol and the
      triterpenoid esters tested are ineffective. alpha-Amyrin and the linoleate and
      palmitate esters of alpha-amyrin and lupeol inhibit cAK in a fashion that is
      competitive with respect to both peptide substrate and ATP (Ki values in the
      range 2-6 microM). However, while lupeol is competitive with respect to ATP it is
      apparently non-competitive with respect to peptide substrate. alpha-Amyrin also
      inhibits CDPK competitively and alpha-amyrin, lupeol and lupeol linoleate are
      competitive inhibitors of PKC. alpha-Amyrin and the palmitate esters of lupeol
      and alpha-amyrin are competitive inhibitors of the potato high affinity cyclic
      AMP-binding phosphatase (Pase) but lupeol inhibits the Pase non-competitively.
      These hydrophobic triterpenoids are further examples of anti-inflammatory
      triterpenoids that are cAK inhibitors.

PMID- 10083839
TI  - 2-Hydroxy-4-methoxybenzaldehyde: a potent tyrosinase inhibitor from African
      medicinal plants.
AB  - By bioassay-guided fractionation using mushroom tyrosinase (EC 1.14.18.1), 2
      hydroxy-4-methoxybenzaldehyde was characterized as the principal tyrosinase
      inhibitor from three East African medicinal plants, the root of Mondia whitei
      (Hook) Skeels (Asclepiaceae), the root of Rhus vulgaris Meikle (Anacardiaceae),
      and the bark of Sclerocarya caffra Sond (Anacardiaceae). It inhibited the
      oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase with an
      ID50 of 4.3 micrograms/ml (0.03 mM). The inhibition kinetics analyzed by a
      Lineweaver-Burk plot found this simple benzaldehyde derivative to be a mixed type
      inhibitor for this oxidation and affects on the enzyme in several ways. Based on
      finding this potent tyrosinase inhibitor, various related analogues were also
      tested in order to gain new insights into their inhibitory functions on a
      molecular basis.

PMID- 10083840
TI  - Inhibition of chemiluminescence in human PMNs by monocyclic phenolic acids and
      flavonoids.
AB  - Flavonoids are metabolized in vivo to monocyclic phenolic acids. We investigated
      whether 18 phenolic acids of the benzoic, phenylacetic, phenylpropanoic or
      cinnamic series-known or potential metabolites of flavonoids-inhibit reactive
      oxygen species (ROS) released by human polymorphonuclear neutrophils (PMNs).
      Chemiluminescence was measured after PMN stimulation with three agents (N
      fMetLeuPhe, phorbol myristate acetate (PMA), or opsonised zymosan) using two
      probes (lucigenin or luminol) with or without horseradish peroxidase (HRP) in
      order to derive specificity profiles for each test compound. The profiles of the
      phenolic acids and flavonoids were compared by a multivariate (correspondence)
      factor analysis. Overall, the phenolic acids were less specific than the
      flavonoids and, with a few exceptions, less potent. Phenolic acids had virtually
      no effect on the chemiluminescence related to O2- formation that is measured by
      lucigenin but inhibited luminol luminescence. Inhibition for all but two phenolic
      acids was sensitive to HRP and might be explained by a scavenger mechanism. Few
      structure-activity relationships emerged suggesting that simple properties such
      as radical scavenging and/or redox activity rather than overall structure might
      be the key determinants of chemiluminescence inhibition. Whatever the mechanism,
      however, we conclude that part of the in vivo pharmacological activity of
      flavonoids may readily be accounted for by phenolic acids.

PMID- 10083841
TI  - Cytotoxicity of natural ginseng glycosides and semisynthetic analogues.
AB  - The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and
      related triterpenes of the dammarane series, isolated from the leaves of the Far
      East species of the genus Betula was studied in order to elucidate structure
      activity relationships. Some of the compounds studied were active against the
      human lung carcinoma GLC4 and adenocarcinoma COLO 320 cell lines. The natural
      glycosides displayed the lowest cytotoxicity. The triterpenes of the dammarane
      series used as starting aglycones for semisynthetic derivatives were moderately
      cytotoxic. The dammarane triterpenes possessing keto groups and their
      semisynthetic glucosides were the most active compounds tested. Cytotoxic effects
      of the dammarane glucosides were inversely proportional both to the number of
      sugars attached to the aglycones and to the number of hydroxy groups of the
      aglycones. The type of side chain and the configuration of the hydroxy group at C
      3 in aglycones did not have a significant influence on the cytotoxicity.

PMID- 10083842
TI  - Antineoplastic agents. III: Steroidal glycosides from Solanum nigrum.
AB  - By bioactivity-guided fractionation, three known steroidal glycosides, beta 2
      solamargine (1), solamargine (2), and degalactotigonin (3), were isolated from
      Solanum nigrum. Compounds 1-3 induced morphological abnormality in Pyricularia
      oryzae mycelia with MMDC (minimum morphological deformation concentration) values
      of 63.0, 38.5, and 97.2 microM, respectively. This is the first report on the
      isolation of 1 from this species and on the cytotoxicity of 1-3 on six cultured
      human solid tumor cell lines HT-29 (colon), HCT-15 (colon), LNCaP (prostate), PC
      3 (prostate), T47D (breast), and MDA-MB-231 (breast) in vitro. The cytotoxic
      assay indicated that 2 is the main antineoplastic agent in S. nigrum. The
      structures of 1-3 were elucidated on the basis of chemical evidence and spectral
      analysis, especially by 2D-NMR analysis.

PMID- 10083843
TI  - Pinusolide from the leaves of Biota orientalis as potent platelet activating
      factor antagonist.
AB  - We investigated the effect of a new PAF antagonist pinusolide, isolated from the
      leaves of Biota orientalis, on PAF-induced [3H]serotinin release from rabbit
      platelets, hypotension and vascular permeability. Pinusolide (IC50, about 5 x 10(
      6) M) inhibited specifically [3H]serotinin release from rabbit platelets when
      stimulated with PAF (5 x 10(-8) M), but showed no effect when induced by ADP,
      collagen, and thrombin. It also inhibited PAF-induced hypotension in a dose
      dependent manner in rats with no effect on the hypotension induced by
      acetylcholine, histamine and serotonin. The inhibitory effect of pinusolide on
      the PAF-induced vascular permeability is less specific than the induced
      hypotension. These results suggest that pinusolide may prove of therapeutic value
      in the treatment of hypotension and a molecular design of pinusolide analogues
      may provide the possibility of a new PAF specific antagonists.

PMID- 10083844
TI  - Antiviral tannins from two Phyllanthus species.
AB  - Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria
      (Euphorbiaceae) have been shown, for the first time, to be active against Epstein
      Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have
      the same moiety of a corilagin, and differ from each other by different
      substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular
      modeling reveal that the essential pharmacophore of these tannins resides in the
      corilagin moiety. The outer complex carboxylic acid moieties appear to act only
      as auxopharmacore.

PMID- 10083845
TI  - Acetogenins and other compounds from Rollinia emarginata and their antiprotozoal
      activities.
AB  - Bioactivity-directed fractionation of the MeOH extract of the stem barks of
      Rollinia emarginata resulted in the isolation of six compounds, four acetogenins,
      rolliniastatin-1, sylvaticin, squamocin, and rollidecin B, one lignan,
      lirioresinol B, and an oxoaporphine, liriodenin. Their structures were determined
      by spectroscopic analysis and their in vitro leishmanicidal and trypanocidal
      properties are reported.

PMID- 10083846
TI  - Study of the antinociceptive action of the ethanolic extract and the triterpene
      24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens.
AB  - We describe here the antinociceptive action of the crude extract (CE), the
      chemical isolation and characterisation and preliminary pharmacological analysis
      of 24-hydroxytormentic acid, isolated from the stem bark of Ocotea suaveolens
      (Lauraceae). The CE given by i.p. or p.o. routes, 30 min and 1 h prior, produced
      significant inhibition of abdominal constrictions caused by acetic acid and also
      inhibited both phases of formalin-induced licking in mice. The antinociception
      caused by the CE, given by i.p. and p.o. routes, lasted up to 4 and 2h,
      respectively. When assessed in the hot-plate test, the CE was inactive. Its
      antinociceptive action was not associated with non-specific effects such as
      muscle relaxation or sedation. The antinociception of CE was not influenced by
      naloxone, L-arginine or DL-p-chlorophenylalanine methyl ester, when assessed
      against the formalin assay. The triterpene 24-hydroxytormentic acid, given i.p.
      30 min before testing, produced significant, dose-related and equipotent
      antinociceptive action against both phases of formalin-induced licking in mice.
      These results demonstrate, for the first time, the occurrence of the triterpene
      24-hydroxytormentic acid in the stem bark of Ocotea suaveolens, and show that the
      CE and 24-hydroxytormentic acid exhibit marked antinociception against the
      neurogenic and the inflamamtory algesic responses induced by formalin in mice.
      The mechanism by which this compound and CE produces antinociception still
      remains unclear, but is unlikely to involve the activation of opioid, nitric
      oxide or serotonin systems or non-specific peripheral or central depressant
      actions.

PMID- 10083847
TI  - A new flavanone isolated from rhizoma smilacis glabrae and the structural
      requirements of its derivatives for preventing immunological hepatocyte damage.
AB  - From the rhizome of Smilax glabra Roxb., a new flavanone was isolated and named
      as smitilbin (1), together with 6 known compounds, engeletin (2), astilbin (3),
      dihydroquercetin (4), eurryphin (5), resveratrol (6), and 5-O-caffeoylshikimic
      acid (7). These compounds were applied to the assay of liver nonparenchymal cells
      (NPC) against hepatocytes (HC) isolated from mice with an immunological liver
      injury. Against the NPC-caused elevation of ALT (alanine transminase) in culture
      supernatant from HC, the pretreatment of NPC with flavanoids (1-3) dose
      dependently blocked the ALT release while 4, the aglycone of 3, did not. The
      chromone 5 showed a much stronger inhibition. Compound 6 also showed the
      activity. However, 1-7 did not show any suppression of NPC or CCl4-induced ALT
      release when they were used to pretreat HC. These results suggest that compounds
      1-3, 5, and 6 could protect the hepatocyte damage from NPC through selectively
      producing the dysfunction of NPC with an essential requirement of rhamnose, and
      the chromone part in their structures may be critical for exhibiting the activity
      rather than through protecting the hepatocyte membranes.

PMID- 10083848
TI  - Mono- and sesquiterpenes and antifungal constituents from Artemisia species.
AB  - In addition to beta-sitosterol and alpha-amyrin detected in all the investigated
      species, the extract of the aerial parts of Artemisia giraldii var. giraldii gave
      stigmasterol, daucosterol, sesamine, luteolin, eupafolin, hispidulin, eupatilin,
      belamcanidin, pinitol, artemin, ridentin, and a new antifungal monoterpene (named
      santolinylol) while that of the aerial parts of A. mongolica afforded sesamine,
      eupafolin, eupatilin, matricarin, and a new germacranolide (3-oxo-11 alpha H
      germacra-1(10)E,4Z-dien-12,6 alpha-olide), and that of the aerial parts of A.
      vestita yielded stigmasterol, daucosterol, umbelliferone, scopolin, scoparone,
      and isoscopoletin-O-glucoside. Pinitol, first reisolated from Artemisia genus,
      was shown to inhibit the growth of the human pathogenic fungi Candida albicans,
      Aspergillus flavus, A. niger, Geotrichun candidum, Trichophyton rubrum, and
      Epidermophyton floccosum. Umbelliferone was also active against Candida
      tropicalis, A. flavus, G. candidum, T. rubrum, and E. floccosum. The flavones
      hispidulin and belamcanidin were almost equally inhibitory to the growth of A.
      flavus, G. candidum, T. rubrum, and E. floccosum, and santolinylol to C.
      albicans, A. flavus, A. niger, G. candidum, T. rubrum, and E. floccosum. In
      addition, ridentin was active against the growth of the plant pathogenic fungus
      Cladosporium cucumerinum.

PMID- 10083849
TI  - Chemical analysis and antimicrobial activity of the resin Ladano, of its
      essential oil and of the isolated compounds.
AB  - Fractionation of the resin Ladano from Cistus creticus subsp. creticus and
      susceptibility testing using the chromatographic fractions showed that its
      antistaphylococcal activity was mainly due to the diterpene sclareol. The
      antimicrobial activity of its essential oil, of the chromatographic fractions,
      and of the isolated compounds was also evaluated against Staphylococcus aureus,
      Staphylococcus epidermidis, and Staphylococcus hominis.

PMID- 10083850
TI  - Antiamoebic and antigiardial activity of plant flavonoids.
AB  - The in vitro antiprotozoal activity of 18 natural flavonoids has been determined
      against Entamoeba histolytica and Giardia lamblia. (-)-Epicatechin, (-)
      epigallocatechin and kaempferol were the most active flavonoids against both
      protozoa.

PMID- 10083851
TI  - Synergistic effects of the alkaloid sinomenine in combination with the
      immunosuppressive drugs tacrolimus and mycophenolic acid.
AB  - The alkaloid sinomenine extracted from the medicinal plant Sinomenium acutum is
      used in China for the treatment of various rheumatic diseases. It has
      immunomodulatory properties in a cardiac allograft transplantation model. Its
      antiproliferative effect on human mononuclear cells in combination with different
      immunosuppressive drugs was further analysed in vitro. Sinomenine dose
      dependently attenuated thymidine incorporation, interleukin-2 synthesis, and cell
      cycle progression of activated T-lymphocytes. Cell proliferation was
      synergistically decreased by addition of sinomenine together with suboptimal
      concentrations of the established immunosuppressive drugs tacrolimus or
      mycophenolic acid, respectively.

PMID- 10083852
TI  - Inhibition of chitin synthase II by catechins from stem bark of Taxus cuspidata.
AB  - Two flavonoids, (+/-)-catechin and (-)-epicatechin, were isolated from the stem
      bark of Taxus cuspidata by monitoring chitin synthase II inhibitory activity. The
      compounds inhibit chitin synthase II with an IC50 of 15 and 29 micrograms/ml,
      respectively and appear to be selective for chitin synthase II. They did not
      inhibit chitin synthase III.

PMID- 10083853
TI  - International Anesthesia Research Society 73rd Clinical and Scientific Congress.
      Los Angeles, California, USA. March 12-16, 1999. Abstracts.

PMID- 10083854
TI  - Chemotherapy Foundation Symposium XVI. Innovative Cancer Therapy for Tomorrow.
      New York City, New York, USA. November 11-13, 1998. Abstracts.

PMID- 10083855
TI  - 100th Annual meeting of the American Society for Clinical Pharmacology and
      Therapeutics. San Antonio, Texas, USA. March 18-20, 1999. Abstracts.

PMID- 10083856
TI  - American Urological Association 94th annual meeting. Dallas, Texas, USA. May 1-6,
      1999. Abstracts.

PMID- 10083857
TI  - [Speech by the President of the Republic, Mr. Jacques Chirac, on the occasion of
      the 100th anniversary of the discovery of radioactivity. Paris, La Sorbonne, 30
      September 1998].

PMID- 10083858
TI  - [Centenary of the discovery of radioactivity. Its impact on biology and
      medicine].

PMID- 10083859
TI  - [Marie Sklodowska-Curie and the Institute of Radium of Warsaw].

PMID- 10083860
TI  - [The centenary of the discovery of radium].
AB  - Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at
      the Paris Academie des Sciences on 26th December 1898. One century later, radium
      has been abandoned, mainly for the reason of radiation safety concerns. It is,
      however, likely that modern techniques of brachytherapy are the successors of
      those designed for radium sources, and that radium has cured thousands and
      thousands patients all over the word for about 80 years. The history of discovery
      and medical use of radium is summarised.

PMID- 10083861
TI  - [Interactions of carboplatin, cisplatin, and ionizing radiation on a human cell
      line of ovarian cancer].
AB  - AIM OF THE STUDY: Cisplatin (CDDP) and radiotherapy are frequently used
      concomitantly in the treatment of various malignant conditions. Because of its
      toxicity, cisplatin tends to be replaced by carboplatin (CBDCA) in several
      indications. Available data regarding the combined effects of cisplatin and
      carboplatin with ionising radiation are contradictory. MATERIALS AND METHODS:
      Various concentrations of cisplatin and carboplatin and various timing of
      association with radiation have been tested in vitro in a human ovarian cancer
      cell line. The parental cell line (AOvC-0) and a cisplatin-resistant stable
      subline (AOvC-CDDP/0) (De Pooter et al., Canc Res, 1991) were exposed to
      carboplatin (2.5, 5 and 10 M) and to CDDP (1, 2.5 and 5 M), 16 h and 4 h before
      and 4 h and 16 h after irradiation, respectively. Cell survival was evaluated by
      a classical clonogenic assay. RESULTS: Exposure of AOvC-0 to 5 M CBDCA and of
      AOvC-CDDP/0 to 10 M CBDCA, before or shortly after radiation exposure, increased
      cell lethality in a clear supra-additive way, with the highest DEF in the
      shoulder region of the survival curve and at radiation doses relevant to clinical
      radiotherapy. In the sensitive cell line, 5 M carboplatin resulted in an
      additional lethality equivalent to 4.5 Gy; in the resistant cells, 10 M
      carboplatin was equivalent to 3.6 Gy. Replacing carboplatin by cisplatin in an
      identical set-up demonstrated exclusively simple additivity (DEF = 1).
      CONCLUSION: These data suggest that carboplatin and cisplatin delivered at
      equitoxic doses interact with radiation in a different way and that, in the
      present set-up, only carboplatin enhanced the effects of radiation. Carboplatin
      might consequently be a better candidate than cisplatin in some concomitant
      combinations with radiotherapy.

PMID- 10083862
TI  - [Locoregional recurrence of adenocarcinomas of the rectum treated with
      irradiation combined with or without excision surgery].
AB  - PURPOSE: Retrospective study to analyze the results of external beam radiation
      treatment with or without surgery for loco-regional recurrence of adenocarcinoma
      of the rectum following previous surgery without pre- or post-operative
      radiotherapy. PATIENTS AND METHODS: Between March 1973 and November 1991, 211
      patients with loco-regional recurrence of rectum cancer were treated with
      external beam radiation treatment. Radical surgery was the only initial treatment
      modality. Surgical resection of local recurrence was done in 36 patients and only
      17 patients could undergo complete resection. Forty-seven patients underwent
      radiotherapy (RT) combined with surgery and 164 received external beam radiation
      treatment alone to a mean total dose of 46 Gy. RESULTS: Among the 151 patients
      whose recurrence was revealed by pain, 64 (42%) were considered to have a
      complete symptomatic response after loco-regional treatment with radiosurgery or
      RT alone. The mean duration of response was 12 months. The 3-year overall
      survival rate was 16%. Five prognostic factors decreased the overall survival
      rate in multivariate analysis: high age, sex (male), concomitant distant
      metastasis, no tumor resection, and low total radiation dose with external beam
      radiation treatment alone. The 3-year overall survival rate for patients with
      completely resected recurrences was 39%. CONCLUSION: External beam RT treatment
      can only be considered a palliative symptomatic treatment. New techniques of
      early detection of local recurrence and new combined modalities approaches
      (radiation sensitizers or intra-operative radiotherapy) with surgical resection
      in some favorable cases should be studied.

PMID- 10083863
TI  - [In vitro study of a paclitaxel-radiotherapy combination on a human epidermoid
      tumor cell line].
AB  - PURPOSE: Paclitaxel is an agent which stabilizes microtubules, and has been shown
      to block different cells in the G2/M phase of the cell cycle and thus to modulate
      their radioresponsiveness. We investigated the radiosensitizing potential of
      paclitaxel in human head and neck cancer cells. MATERIALS AND METHODS: ZMK-1
      cells were incubated with paclitaxel for 3, 9, or 24 h before or during 24 h
      after irradiation. Paclitaxel concentrations of 70 nM, 7 nM, and 0.7 nM were
      chosen to obtain equivalent toxicity at the different incubation times: 3 h, 9 h,
      and 24 h, respectively. Radiation doses ranged from 0 to 8 Gy using 60Co source.
      Cell survival was measured by a standard clonogenic assay after a 9-day
      incubation. Flow cytometry was used to measure the capacity of paclitaxel to
      accumulate cells in the G2/M phase. RESULTS: Paclitaxel alone possessed
      cytotoxicity dependent on time and concentration. There was a total of 40% of
      cells accumulated in G2/M after 24-36 h. When combined with radiation, the 9 h
      preincubation resulted in a radiosensitization. The 3 h pre-incubation as well as
      the 24 h post-incubation resulted in an infra-additive effect. CONCLUSION: In our
      cells a radiosensitizing effect of paclitaxel could not be demonstrated
      unambiguously. The blockage of the cells in the G2/M phase is not the only
      mechanism to explain the potential radiosensitization of paclitaxel.

PMID- 10083864
TI  - [Sensitivity to etoposide of human malignant glioma cell lines. Mechanisms of
      action].
AB  - AIM OF THE STUDY: Etoposide, a Topoisomerase II inhibitor agent, is currently
      being explored as a therapeutic agent for brain tumors. The aim of this
      experimental study was to compare the in vitro etoposide sensitivity of human
      glioma cells vs human squamous cell carcinoma (SCC) cells. MATERIAL AND METHODS:
      Twelve human cell lines (six malignant glioma cell lines and six head and neck
      SCC cell lines) were used for this comparative study. A standard colony formation
      assay was used to assess cell survival. Since Topoisomerase II is the critical
      target for etoposide, it was of interest to determine Topoisomerase II activity
      and etoposide induced inhibition of Topoisomerase II activity for the glioma
      cells vs the SCC cells. RESULTS: Except for etoposide-induced inhibition of
      Topoisomerase II activity, no difference was found for etoposide sensitivity and
      Topoisomerase II activity between the both type of cells. CONCLUSION: These
      results suggested that the Topoisomerase II reactive agents may prove to be
      clinically a useful drug for patients presenting with malignant gliomas.

PMID- 10083865
TI  - [40th meeting of the American Society for Therapeutic Radiology and Oncology,
      Phoenix (Arizona), 25-29 October 1998].

PMID- 10083866
TI  - European interlaboratory comparison of breath 13CO2 analysis.
AB  - The BIOMED I programme Stable Isotopes in Gastroenterology and Nutrition (SIGN)
      has focused upon evaluation and standardisation of stable isotope breath tests
      using 13C labelled substrates. The programme dealt with comparison of 13C
      substrates, test meals, test conditions, analysis techniques, and calculation
      procedures. Analytical techniques applied for 13CO2 analysis were evaluated by
      taking an inventory of instrumentation, calibration protocols, and analysis
      procedures. Two ring tests were initiated measuring 13C abundances of carbonate
      materials. Evaluating the data it was found that seven different models of
      isotope ratio mass spectrometers (IRMS) were used by the participants applying
      both the dual inlet system and the continuous flow configuration. Eight different
      brands of certified 13C reference materials were used with a 13C abundance
      varying from delta 13CPDB -37.2 to +2.0/1000. CO2 was liberated from certified
      material by three techniques and different working standards were used varying
      from -47.4 to +0.4/1000 in their delta 13CPDB value. The standard deviations
      (SDs) found for all measurements by all participants were 0.25/1000 and 0.50/1000
      for two carbonates used in the ring tests. The individual variation for the
      single participants varied from 0.02 /1000 (dual inlet system) to 0.14/1000
      (continuous flow system). The measurement of the difference between two
      carbonates showed a SD of 0.33/1000 calculated for all participants. Internal
      precision of IRMS as indicated by the specifications of the different instrument
      suppliers is < 0.3/1000 for continuous flow systems. In this respect it can be
      concluded that all participants are working well within the instrument
      specifications even including sample preparation. Increased overall
      interlaboratory variation is therefore likely to be due to non-instrumental
      conditions. It is possible that consistent differences in sample handling leading
      to isotope fractionation are the causes for interlaboratory variation. Breath
      analysis does not require sample preparation. As such, interlaboratory variation
      will be less than observed for the carbonate samples and within the range
      indicated as internal precision for continuous flow instruments. From this it is
      concluded that pure analytical interlaboratory variation is acceptable despite
      the many differences in instrumentation and analytical protocols. Coordinated
      metabolic studies appear possible, in which different European laboratories
      perform 13CO2 analysis. Evaluation of compatibility of the analytical systems
      remains advisable, however.

PMID- 10083867
TI  - 13C urea breath test.

PMID- 10083868
TI  - 13C mixed triglyceride breath test.

PMID- 10083869
TI  - 13C carbohydrate breath tests.

PMID- 10083870
TI  - 13C protein breath tests.

PMID- 10083871
TI  - 13C breath test for measurement of liver function.

PMID- 10083872
TI  - 13C octanoic acid breath test.

PMID- 10083873
TI  - [Prolonged suppressive L-thyroxine therapy. Longitudinal study of the effect of
      LT4 on bone mineral density and bone metabolism markers in 71 patients].
AB  - OBJECTIVES: A prospective longitudinal study was conducted to investigate the
      influence of prolonged suppressive L-thyroxin therapy on bone density and
      biochemical markers of bone remodeling. PATIENTS AND METHODS: Seventy-one
      patients (including 28 menopaused women) taking long-term L-T4 for thyroid
      carcinoma were divided into 3 groups according to their TSH level: low (TSH <
      0.04 mlU/l), moderate (0.04 TSH < or = 0.10 mlU/l) and high (TSH > 0.10 mlU/l).
      Bone density was measured in lumbar vertebrae annually for a mean 4.5 years. Bone
      metabolism markers were measured over a 4 year period. Bone density measurements
      of the femur were also obtained for 2 years in 16 menopaused women. RESULTS:
      Lumbar bone density did not decline whatever the TSH level or the duration of L
      T4 treatment. Likewise for menopaused women without substitution
      estroprogesterone therapy. Over the 4 years, biochemical markers of bone
      formation, including bone alkaline phosphatases and osteocalcin, or of bone
      resorption, including urinary hydroxyprolin, did not vary. In addition, in
      menopaused women, femoral bone density was not significantly lowered over the 2
      years follow-up. No lumbar or femoral osteopenia was observed in these patients
      taking L-thyroxin, even for those with complete TSH blockade. Biochemical markers
      did not demonstrate a significant acceleration of bone turnover during prolonged
      administration of L-T4 at suppressive levels.

PMID- 10083874
TI  - [Paraneoplastic opsoclonus-myoclonus syndrome revealing T-cell lymphoma].
AB  - BACKGROUND: Nonrhythmic involuntary ocular oscillations and axial and segmentary
      myoclonia are associated in the opsoclonus-myoclonus syndrome. In adults, a
      paraneoplastic origin is generally found. We report the first of opsoclonus
      myoclonus associated with non-Hodgkin's lymphoma. CASE REPORT: A 66-year-old
      woman rapidly developed a typical opsoclonus-myoclonus syndrome within a few
      hours, presenting vertigo, cerebellous ataxia, multidirectional involuntary
      ocular movements and non-rhythmic axial and segmentary myoclonia. Brain computed
      tomography and magnetic resonance imaging demonstrated discrete diffuse anomalies
      of the white substance predominating in the pons. The cerebrospinal fluid showed
      discrete lymphocytosis. Antineuron antibodies were negative. No cause could be
      identified until the development 11 months later of pleomorphic T-cell mediastino
      cervical lymphoma. The patient responded moderately to a CHOP regimen which had
      no effect on the opsoclonus-myoclonus syndrome. Death occurred after a 16-month
      course due to pulmonary complications. DISCUSSION: Neuroblastoma and infectious
      causes predominate in opsoclonus-myoclonus syndromes observed in children; in
      adults, the predominant cause is cancer. Antineuron, anti-Ri and anti-Hu
      antibodies can be evidenced in some cases, arguing in favor of a paraneoplastic
      mechanism. Recent reports have evidenced MRI anomalies in the pons and the
      cerebellum, anatomically well correlated with the opsoclonus-myoclonus syndrome.
      Besides small-cell bronchogenic anaplastic cancer, the possibility of cancer of
      the breast and uterus, and both non-Hodgkin and Hodgkin lymphoma should be
      explored, knowing the cancer develops several month after the opsoclonus
      myoclonus syndrome.

PMID- 10083875
TI  - [Veno-occlusive disease of the liver and POEMS syndrome].
AB  - BACKGROUND: Veno-occlusive disease of the liver is a common cause of morbidity
      and mortality after chemotherapy and/or radiotherapy and bone marrow
      transplantation. Non thrombotic hepatic venous obstruction is characteristic, but
      pathogenesis of this disease remains unknown. CASE REPORT: In june 1993, a 58
      year-old man was treated by cyclophosphamide and steroid for a POEMS syndrome. In
      november 1996, he developed hepatalgia, edema, ascitis and jaundice. The
      diagnosis of hepatic veno-occlusive disease was obtained by hepatic biopsy.
      Refractory ascitis was treated by transjugular intrahepatic portosystemic shunt.
      Gradual improvement in clinical status was observed after this therapy.
      CONCLUSION: This observation offers three original types of information: there
      has been no prior report of an association between veno-occlusive disease and
      POEMS syndrome, the role of low dose cyclophosphamide in hepatic veno-occlusive
      disease was certain, transjugular intrahepatic portosystemic shunt is an
      interesting therapy with one years remission.

PMID- 10083876
TI  - [Primary Gougerot-Sjogren syndrome in a young man].

PMID- 10083877
TI  - [Polystyrene sodium sulfonate enema: with or without sorbitol?].

PMID- 10083878
TI  - [Postpartum thyroiditis: a silent entity].

PMID- 10083879
TI  - [Generalized social phobias, are they sufficiently recognised and treated?].

PMID- 10083880
TI  - [Prescription and consumption of antibiotics in ambulatory care].
AB  - OBJECTIVE: This study was conducted to describe changes in prescription practices
      outside the hospital, to evaluate the adaptation of such prescriptions to current
      scientific knowledge, and to compare medical practices in France with those in
      other European countries. METHODS: Data were collected from several sources:
      analysis of the literature, surveys conducted in the Loiret department and in the
      Rhone-Alpes region, ten-year health surveys (INSEE), data from the Sentinel
      network, sales statements from pharmaceutical firms, the Permanent Survey of
      Medical Prescription (EPPM) of the Medical Information and Statistics (IMS) firm.
      Comparisons between France, the United Kingdom and Germany were conducted by the
      French Medicine Agency's Pharmaco-economic Studies and Information Department
      using data furnished by the IMS firm and by pharmaceutical firms. RESULTS: In
      France, antibiotic sales increased by a mean annual rate of 2.1%, expressed in
      antibiotic units, and 2.6%, expressed in turnover (manufacturer price) between
      1991 and 1996. The majority of these antibiotics were prescribed for respiratory
      and ENT infections with a presumed viral etiology such as rhinopharyngitis and
      acute bronchitis. The results of the different surveys were in agreement showing
      that antibiotic prescriptions are made in approximately 40% of all consultations
      for rhino-pharyngitis and in 80% of those for acute bronchitis. Antibiotics were
      prescribed in more than 90% of cases of pharyngitis whatever the age of the
      patient. The situation was different for acute middle ear infections as the
      number of consultations has remained relatively unchanged over the last 10 years
      while antibiotic prescriptions have strongly increased, reaching 80% of the
      consultations. The number of consultations for pharyngitis and acute rhino
      pharyngitis appears to be greater in France than in the United Kingdom and in
      Germany. Likewise, the proportion of patients using antibiotics after consulting
      for presumed viral conditions would be higher in France with different antibiotic
      classes being used. CONCLUSIONS: There is a gap between official guidelines
      (product description documents, therapeutic information document good practice
      guidelines, consensus conferences) and the state of current practices. Excessive
      and poorly-adapted antibiotic prescription favors the disturbing phenomenon of
      resistance which is all the more alarming because the emergence of resistant
      strains is difficult to predict and concern bacteria causing the most common
      infections. To improve medical practices and achieve a persistent reduction in
      the use of antibiotics for viral infections, validated recommendations should be
      distributed to physicians. An effort should be made to prescribe the most
      appropriate active substance at optimal dose and treatment duration to limit the
      development of bacterial resistance. In addition, patients and the general public
      should be informed of the absence of any beneficial effect and the individual and
      collective risks involved in using antibiotic for viral infections in order to
      help them better understand and comply to their physician's prescription.

PMID- 10083881
TI  - [Antibiotic therapy of upper respiratory tract infections in ambulatory care.
      Report of the National Observatory on Drug Prescription and Consumption].

PMID- 10083882
TI  - [New classification and diagnostic criteria of diabetes. Interview with Prof. B.
      Charbonnel].

PMID- 10083883
TI  - [Ecstasy and its "counterparts"].
AB  - RISK AWARENESS: Use of psychostimulants is spreading in France, particularly at
      "techno" dances. The generic term "ecstasy" covers a wide variety of molecules
      with variable formulations. The situation is a true public health problem,
      generally concerning very young subjects who must be informed of the risks
      involved. Knowledge of the chemical makeup of the products currently used is
      needed to provide valid information and reduce risks. CHEMICAL ANALYSIS: Two
      types of chemical analysis are used for rapid controls. A coloration test is used
      by the Rave mission implemented by "Medecins du Monde". More elaborate analysis
      methods are used to identify the active substances and quantify the compounds in
      the different "tablets". FINDINGS: Rapid controls give a means of quickly
      identifying samples containing methylenedioxyamphetamines and distinguishing them
      from other samples which may contain any number of substances with unknown
      toxicity. A precise analysis of 73 samples has shown highly variable compositions
      with 22% actually containing methylenedioxyamphetamines. PREVENTION: Precise
      analytical knowledge of the drugs circulating in "techno" dances has revealed the
      extreme danger of a large number of the substances used. A continuous control of
      ongoing consumption is required to correctly warn the users and reduce risk.

PMID- 10083884
TI  - [Paraneoplastic pemphigus].
AB  - A RARE DISEASE: Paraneoplastic pemphigus is an rare autoimmune bullous skin
      disease recently recognized. About 50 cases have been reported since its first
      description in 1990. CLINICAL MANIFESTATIONS: Clinical signs are polymorphous
      resembling the cutaneomucosal manifestations of pemphigus vulgar (skin and mucosa
      erosions, fragile interdermal bullae), pemphigoid (urticaria, distended
      subepidermal bullae), and polymorphous erythema (plaque lesions). Mucosal
      erosions predominate however. ASSOCIATED CANCERS: Most cancers associated with
      paraneoplastic pemphigus are hematologic diseases (non-Hodgkin's lymphomas,
      chronic lymphoid leukemia). SEVERE PROGNOSIS: No standard treatment has been
      defined. General corticosteroids and treatment of the causal disease are
      indicated. The clinical course of paraneoplastic pemphigus does not always follow
      the course of the associated neoplasm. POSITIVE DIAGNOSIS: Pathology criteria
      (keratinocyte necrosis, suprabasal keratinocyte vacuolization, intraepidermal
      acantholysis) and immunohistological findings (antibody and complement deposits
      at the dermo-epidermal junction and within the keratinocytes on different
      epithelial substrates) are insufficient for positive diagnosis. Autoantibodies
      must be identified by immunoprecipitation or immunoblotting to identify the
      target antigen complex plakin components (desmoplakin I and II, periplakin,
      envoplakin), the major pemphigoid antigen, desmoglein 3, and certain yet
      unidentified antigens with a molecular weight of 170 kD. PATHOGENESIS:
      Paraneoplastic pemphigus appears as a model autoimmune paraneoplastic disease.
      Its origin remains elusive. It has been hypothesized that tumor-induced
      inhibition of tolerance to certain antigens implicated in the keratinocyte
      junctional systems could be involved.

PMID- 10083885
TI  - [The role of nelfinavir in the triple-therapy of HIV infection].

PMID- 10083886
TI  - [Outcome research: rationales and objectives].
AB  - Outcome research measures the clinical, economic and humanistic outcomes of
      pharmacological therapies on patients suffering from different diseases. Outcome
      research can be applied either to phase II and III clinical trials to assess new
      drugs for registration or to already marketed drugs to assess their real value
      when used in clinical practice in a large population of patients. Oncology can be
      a major field of application because there is a large amount of new treatments
      put on the market, often without demonstration of significant improvement in
      survival or Quality of Life but with higher prices than the old molecules.
      Patients and disease specific outcomes have been identified for cancer by a
      Working Group set up by the American Society of Clinical Oncology, with the
      former being defined as more critical to establish the value of new treatments.
      Survival, drug toxicity and impact on Quality of Life are the most important
      patient's outcomes to consider before recommending anti-cancer therapies for use
      in clinical practice. The present paper will describe the outcomes in oncology
      and will deal with the transferability to clinical practice of the results of
      clinical trials.

PMID- 10083887
TI  - [Supportive care in oncology].
AB  - It is extremely important to deliver treatments, both in medical oncology and in
      radiation oncology, in compliance with the due dose intensity, in order to
      achieve the best results in terms of clinical response and local control and,
      often, also in terms of survival. Supportive care is one of the tools for the
      achievement of this goal, permitting the delivery of aggressive therapies and the
      improvement of Quality of Life. It is the aim of the Tsonc study to evaluate what
      the main therapeutic trend is, on the ground of a survey performed in 105 medical
      oncology, radiation oncology, and haematology centres. For this assessment the
      WHO/INH and RTOG common toxicity criteria were adopted, even knowing that these
      score systems had been developed for reporting acute/subacute toxicity and not to
      choose the therapeutic approach. However, these scales give us the possibility to
      refer to highly validated systems and provide participants with a common
      language. Thirty-two items of toxicity were listed, and each item included 2 to 4
      degrees of severity so to report supportive care accordingly. The present paper
      reports the criteria of choice of the scales and symptoms and the schedule of the
      queries.

PMID- 10083888
TI  - [5-fluorouracil and colorectal tumors: use in clinical practice and the "MISURA"
      project].
AB  - 5-fluorouracil, an antimetabolite inhibiting timidilate synthetase, is one of the
      most used drugs in the treatment of many solid tumor types. In particular it is
      still central in the treatment of colorectal cancer. Nevertheless 5-FU efficiency
      is limited, this is due to the rapidity of its metabolism (T1/2 10 min). Many
      attempts have been done to increase its efficiency: 1) combinations with other
      antitumor drugs have been tested, but no one showed improved response rates with
      respect to 5-FU alone; 2) use of biological modifiers such as folinic acid and
      methotrexate. They interact with the biological actions of 5-FU improving its
      therapeutic effects. These combinations appear to be more effective than 5-FU
      alone; 3) continuous infusion increases the percentage of susceptible tumor
      cells, it makes possible the use of a high intensity dose which is active in
      patients resistant to 5-FU administered as bolus-injection. There are many
      schedules and methods of administration of 5-FU in the treatment of CRC, each of
      them showing different types of toxicities. This explains why there is the need
      to obtain a profile of 5-FU in clinical practice. The project called MISURA is
      though to give us this kind of information. It will be a collection of data
      regarding patients affected by colorectal cancer and treated with 5-FU. The
      collected information will be about diagnosis; ways of use, schedules, doses and
      tolerability of the drug; obtained responses. The aims of the study are: 1) to
      evaluate the use of 5-FU in clinical practice; 2) to collect data about the use
      of supportive therapy; 3) to know the effective incidence and prevalence of CRC
      in Italy. The study is retrospective, the sample consists of all patients from
      the oncological departments chosen to represent the national territory. The
      analysis of the data will be descriptive.

PMID- 10083889
TI  - [Blood transfusion in oncologic surgery: the role of recombinant human
      erythropoietin (rHuEPO)].
AB  - Anemia is common in cancer patients. The pathophysiology is multifactorial,
      however the most common cause is the anemia of chronic diseases (ACD). In 20-50%
      of cancer patients, anemia restricts physical activity and quality of life and
      requires transfusion support. The percentage of patients necessitating
      transfusion dramatically increases when patients require surgery. The traditional
      belief that blood transfusion is an effective and safe therapy has been
      challenged by a heightened awareness of the infectious and immunologic risks
      associated with allogeneic blood administration. In cancer patients transfusion
      induced immunomodulation may have the potential to significantly increase
      postoperative infections and cancer recurrence so that it seems reasonable to
      minimize allogeneic blood exposure. Several strategies have been adopted to
      reduce allogeneic transfusion in surgical patients, however to properly select
      the appropriate blood conservation strategies the blood transfusion requirements
      for each patient should be defined. Allogeneic blood transfusion in surgery can
      be reduced by the introduction of autologous blood (AB) programmes and by the use
      of rHuEPO, alone or in association with AB techniques. AB donation is currently a
      standard of care for elective surgical patients but its efficacy is limited by
      anemia that prevents the donation of the optimal number of AB units. rHuEPO has
      been shown to significantly increase the volume of AB that anemic patients can
      predeposit or, used perisurgically, to expand the circulating RBCs mass before
      surgery. Moreover clinical trials employed rHuEPO in anemic cancer patients with
      various solid tumors both on and off chemotherapy reporting a significantly
      increase in Hct in more than 50% of the treated patients. Recently different
      studies have shown the efficacy of rHuEPO in increasing the volume of AB also in
      patients with ACD and cancer, thus proving to be a useful addition to existing
      strategies of blood conservation to minimize exposure to allogeneic blood in
      surgical cancer patients.

PMID- 10083890
TI  - [Epoetin alfa in radiotherapy].
AB  - Sixty per cent of oncologic patients need radiation therapy for cure or
      palliation. In fact, in most neoplastic diseases, a better local control
      positively impacts on disease-free survival and overall survival. The efficacy of
      radiotherapy depends on several factors: while some are tumor-related, others are
      host-related. Radiobiological phenomena are also important: ionizing radiation is
      responsible for cell damage (double rupture of DNA chains), mostly an indirect
      mechanism with the formation of free radicals. Their toxic action is enhanced by
      the oxygen partial pressure at the cellular level. A number of studies have
      confirmed that good tissue oxygenation is a function of a high hemoglobin level
      in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are
      rarely present in oncologic patients due to the disease-related toxicosis as well
      as to the therapy induced hematologic toxicity. The treatment of anemia is free
      of risk for the recent developments in technology which with gene cloning and the
      technique of recombinant DNA has allowed the production of human recombinant
      erythropoietin. Erythropoietin is produced by the interstitial cells of renal
      tubules in response to hypoxia. It prevents apoptosis and promotes erythroid
      proliferation and differentiation with consequent reticulocyte release and
      hemoglobin synthesis. It is not completely understood whether the efficacy of
      radiotherapy depends on hemoglobin values present at the start of irradiation
      (often less than 12-13 g/dL) or on the higher ones observed during and at the end
      of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non
      anemic patients in terms of costs/benefits is at present non sustainable. To the
      contrary, in patients undergoing radiotherapy to extended fields or aggressive
      multimodal treatments, for the higher risk of anemia, the early use of this
      treatment can be hypothesized in case of initial anemia to improve therapy
      compliance and prevent negative conditioning of results. Keeping in mind that
      grade 1 minimum toxicity for red cells, according to the Radiation Therapy
      Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be
      considered as cutoff to start erythropoietin therapy.

PMID- 10083891
TI  - [Epoietin alfa in lung cancer].
AB  - There is a high frequency of hematopoietic abnormalities in patients with
      neoplastic disorders, anemia being one of the most common and important,
      especially in lung cancer patients undergoing chemotherapy. A number of factors
      are able to affect the incidence and severity of chemotherapy-induced anemia: the
      type of chemotherapy, chemotherapy dose-intensity, chemotherapy duration, prior
      treatment, baseline Hb value and entity of Hb decrease during chemotherapy. An
      impaired erythroid marrow response to erythropoietin (EPO) and reduced EPO levels
      in response to anemia may contribute to the development of this form of anemia in
      lung cancer patients. Recombinant human EPO has been successfully used in the
      treatment of anemia. EPO increases the red cells mass and eliminates by
      approximately 50% the need for blood transfusions in patients with chronic anemia
      of cancer. EPO is also effective in the prevention of anemia of cancer patients.
      Besides increasing the levels of hemoglobin, EPO is also able to significantly
      improve the quality of life and performance status of anemic patients with
      cancer. EPO is well tolerated and the only drawbacks are represented by its cost
      and the need for a prolonged parenteral treatment. The use of EPO can be
      optimized by taking into consideration some predicting factors, by modulating the
      dose and by using iron support. In patients with lung cancer, the objective of
      EPO treatment may vary from palliation to survival improvement according to
      stage, type of antineoplastic treatment and prognosis. To take maximum advantage
      from its efficacy, EPO treatment in lung cancer patients needs to be
      individualized by identifying for each patient the risk of severe anemia and the
      objective of treatment.

PMID- 10083892
TI  - Growth hormone deficiency and cardiovascular risk.
AB  - It is now recognized that growth hormone (GH) deficiency in adults represents a
      distinct clinical syndrome that encompasses reduced psychological well-being as
      well as specific metabolic abnormalities. The latter features, which include
      hypertension, central obesity, insulin resistance, dyslipidaemia and
      coagulopathy, closely resemble those of metabolic insulin resistance syndrome.
      The increased cardiovascular morbidity and mortality demonstrated in these GH
      deficient (GHD) adults reinforce the close association between the two syndromes.
      Replacement of GH in GHD adults has resulted in a marked reduction of central
      obesity and significant reduction in total cholesterol but little change in other
      risk factors, in particular insulin resistance and dyslipidaemia. The persistent
      insulin resistance and dyslipidaemia, together with the elevation of plasma
      insulin levels and lipoprotein (a) with GH replacement in these subjects are of
      concern. Long-term follow-up data are required to assess the impact of GH
      replacement on the cardiovascular morbidity and mortality of GHD adults. Further
      exploration of the appropriateness of the GH dosage regimens currently being
      employed is also indicated.

PMID- 10083893
TI  - Growth hormone: a new therapy for heart failure?
AB  - There is now little doubt that growth hormone (GH) and insulin-like growth factor
      1 (IGF-1) play a role in cardiac development and in cardiovascular physiology in
      adult life. Congenital lack of GH is associated with defective cardiac growth,
      ventricular wall thinning, and impaired systolic function. These abnormalities
      limit exercise capacity and contribute to the poor quality of life in patients
      with GH deficiency. In addition, studies with in vitro muscle preparations have
      shown that IGF-1 affects myocardial contractility by a direct mechanism. These
      findings suggested that GH would benefit patients affected by heart failure.
      Indeed, GH and/or IGF-1 have proven beneficial in various models of experimental
      heart failure. Tested in patients with classes II-IV heart failure, they improved
      cardiac performance and clinical status. These effects were associated with
      improved myocardial energetics and de-activation of the neurohormonal system.
      Because of the uncontrolled nature of the studies and the small number of cases
      examined, conclusions as to the effectiveness of GH and IGF-1 must await the
      results from larger trials.

PMID- 10083894
TI  - Growth hormone therapy and fracture risk in the growth hormone-deficient adult.
AB  - Adults with childhood-onset growth hormone deficiency (GHD) and younger adults
      with adult-onset GHD have a reduced bone mineral content (BMC). Recent trials
      with prolonged GH replacement therapy have demonstrated increased BMC in such
      patients. GH treatment in animals increases the amount of bone and the total
      strength while the density (BMC per unit volume) and the quality of the bone is
      not increased. A sensitive non-invasive parameter for the detection of effects of
      GH on bone in clinical studies is therefore to use the BMC from dual-energy X-ray
      absorption (DEXA) analysis. Bone density is strongly related to fracture risk in
      women. A number of other risk factors for fractures can be identified in adult
      GHD patients which, collectively, might explain the increased fracture frequency
      observed in these patients. The increase in BMC in response to long-term GH
      replacement therapy is promising. Whether more prolonged treatment will result in
      a normalization of the bone mass and reduced fracture frequency remains to be
      established.

PMID- 10083895
TI  - Recombinant human growth hormone as potential therapy for osteoporosis.
AB  - Growth hormone (GH) directly stimulates proliferation and differentiated
      functions of cultured bone cells. In addition, temporal relationships between
      decreased function of the GH/IGF-1 axis and age-related bone loss have prompted
      some investigators to hypothesize that these two phenomena are causally related,
      and to test this hypothesis by evaluating the effects of GH administration on
      bone turnover and mineral density in older men and women. Although these studies
      show clearly that GH initiates bone remodelling activity, changes in bone mass
      have not been impressive, even when GH was given in combination with anti
      resorptive therapy. Thus, it appears very unlikely that GH will offer a
      clinically useful means to restore skeletal deficits in patients with
      osteoporosis.

PMID- 10083896
TI  - How much, and by what mechanisms, does growth hormone replacement improve the
      quality of life in GH-deficient adults?
AB  - The majority of studies (but not all) have demonstrated that adults with
      hypopituitarism of both childhood and adult onset have a diminished quality of
      life (QOL) in comparison with the normal population. Reductions in physical and
      mental energy, dissatisfaction with body image and poor memory have been reported
      most consistently. A specific role for growth hormone (GH) deficiency, as opposed
      to multiple pituitary hormone deficiency, has been observed for the memory
      deficit, which extends to both short- and long-term memory. Comparisons with
      normal siblings have confirmed the reduced QOL, although differences have been
      small. There is less consensus for a reduction in QOL when hypopituitary subjects
      are compared with patients with other chronic diseases, with studies supporting
      (in comparison with diabetics) and refuting (in comparison with patients
      following mastoid surgery) the reduction in QOL. GH replacement in adults has
      improved QOL, particularly in the domains of energy level and self-esteem, and
      memory has improved. The social impact of these changes may be considerable, with
      patients requiring fewer days' sick leave. A major placebo effect is present,
      however, and neutral results as well as positive have been reported in placebo
      controlled trials. Where a positive effect has been observed, it has been more
      likely to occur in patients with a low QOL at the outset. It is otherwise
      impossible to predict at the outset those who will benefit from GH replacement.
      GH treatment has effects on body composition, exercise capacity, muscle strength,
      total body water and intermediary metabolism which would be expected to improve
      QOL. Replacement therapy also has side-effects, and it is the variable balance of
      the positive and negative effects, coupled with the difficulties of measuring
      QOL, which have led to the disparate results in the literature. There is probably
      also a true inter-individual variation, although the mechanisms of this are
      currently unknown.

PMID- 10083897
TI  - Ageing and growth hormone status.
AB  - Organic growth hormone (GH) deficiency in adults results in many adverse changes
      similar to the changes which occur in humans with increasing age. The secretion
      of GH from the anterior pituitary declines with increasing age. This observation,
      together with the changes in body composition associated with organic GH
      deficiency in adults, has led to the suggestion that the elderly without
      hypothalamic-pituitary disease are GH deficient and may benefit from GH therapy.
      The impact of organic disease of the hypothalamic-pituitary axis in the elderly
      may result in a reduction in GH secretion of up to 90%. This reduction in GH
      secretion is sufficient to cause a fall in the serum insulin-like growth factor-1
      (IGF-1) concentration, abnormal body composition and abnormal bone turnover,
      although bone mineral density is unaffected. These changes are distinct from
      those associated with the hyposomatotropism of the elderly, but are less severe
      than those seen in younger adults with organic GH deficiency. In this chapter we
      discuss the effects of organic GH deficiency in elderly subjects and the
      potential effects of GH replacement therapy. We also examine the potential for GH
      therapy to correct some of the detrimental effects of the ageing process.

PMID- 10083898
TI  - Interaction between body composition, leptin and growth hormone status.
AB  - Administration of growth hormone (GH) induces changes in body composition,
      namely, increases in both bone and lean mass and a decrease in fatty tissue.
      However, the contrary issue, i.e. the way in which body composition affects the
      secretion of GH, is highly controversial. Disease states such as obesity and
      chronic hypercortisolism are associated with increased adiposity and/or the
      central distribution of fat. Ageing, characterized by excess adiposity, is also
      associated with impaired secretion of GH. In these states, both spontaneous and
      stimulated secretion of GH is severely impeded. At the other extreme,
      malnutrition and fasting are both associated with increased secretion of GH when
      confronted with most, if not all, stimuli. As the common factor in all of these
      situations is the increased or decreased adiposity, or the changes in energy
      homeostasis, it has been postulated that adipose tissue exerts a relevant role in
      the control of GH secretion in man. The link between adipose tissue and GH seems
      to be exerted through at least two signals produced by adipocytes: free fatty
      acids (FFA) and the recently cloned protein, leptin. An increase in FFA blocks
      secretion of GH, while a decrease in FFA enhances secretion. Leptin, a hormone
      whose main role is to regulate the intake of food and energy expenditure, seems
      to regulate GH secretion by acting at the hypothalamic level. In summary, body
      composition affects GH secretion by way of the degree of adiposity, and free
      fatty acids and leptin would appear to be the messages through which adipocytes
      participate in the regulation of GH secretion. This framework clarifies the
      metabolic control of GH, a hormone with profound metabolic activities.

PMID- 10083899
TI  - Acquired growth hormone resistance in adults.
AB  - Acquired growth hormone resistance (AGHR) may be defined as the combination of a
      raised serum growth hormone (GH) concentration, low serum insulin-like growth
      factor-1 (IGF-1) concentration and a reduced anabolic response to exogenous GH. A
      wide range of conditions exhibit the syndrome to a variable degree, including
      sepsis, trauma, burns, AIDS, cancer, and renal or liver failure. The primary
      defect seems to be a reduction in IGF-1 concentration which then leads to
      increased GH concentration by a loss of negative feedback. It is not clear
      whether IGF-1 concentration falls because of decreased production or increased
      clearance from the circulation, or both. Treatment to reverse the biochemical
      defect by restoring IGF-1 levels, either by the administration of GH or IGF-1,
      has resulted in improvements in a wide range of metabolic parameters and, more
      recently, to definite clinical benefit in well-defined groups, such as patients
      with AIDS. These results cannot be extrapolated to other groups with AGHR as a
      recent unpublished report suggested increased mortality in critically ill
      patients treated with GH. Research needs to focus on the molecular basis of AGHR
      if we are to develop therapies for catabolism.

PMID- 10083900
TI  - Growth hormone and ovarian function.
AB  - Growth and reproductive development are closely co-ordinated during puberty but
      there is also evidence that growth hormone (GH) may have a physiological role in
      adult ovarian function. Both GH and the insulin-like growth factors (IGFs) have
      been shown to augment granulosa cell proliferation and steroidogenesis in the
      human Graafian follicle, suggesting that GH may act as a 'co-gonadotrophin' at
      ovarian level. Furthermore, the intra-ovarian 'IGF system' (i.e. IGFs and IGF
      binding proteins) may be implicated in folicular atresia and in disorders of
      follicular function associated with polycystic ovary syndrome (PCOS). The
      clinical importance of GH to ovarian function in the adult is illustrated by the
      finding that adjuvant GH treatment reduces the dose of exogenous gonadotrophin
      which is required to induce folliculogenesis in women with hypogonadotrophic
      hypogonadism. There is, however, no evidence that GH supplementation is of
      significant clinical benefit in the management of patients with other ovulatory
      disorders--including PCOS--or in superovulation protocols for in vitro
      fertilization.

PMID- 10083901
TI  - Diagnostic and therapeutic uses of growth hormone-releasing substances in adult
      and elderly subjects.
AB  - The aim of this review is to answer two questions. The first question is: is
      there any alternative provocative test equal to, or even better than, the insulin
      tolerance test (ITT), the so-called gold standard, for the diagnosis of growth
      hormone deficiency (GHD) in adults and the elderly? The answer is 'yes'. In fact,
      when combined with arginine or pyridostigmine, growth hormone-releasing hormone
      (GHRH) becomes one of the most potent and reproducible tests for distinguishing
      patients with severe GHD from normal subjects. Owing to its tolerability and its
      suitability for use in the elderly, the GHRH + arginine test is the best
      alternative choice and is at least as sensitive as the ITT provided that
      appropriate cut-off limits are given. The second question is: is there any
      therapeutic approach alternative to recombinant human growth hormone (rhGH) for
      adult and elderly patients with GHD and/or for the somatopause? At present, the
      answer is 'no'. Growth hormone (GH)-releasing substances need the functional
      integrity of somatotroph cells to induce the release of growth hormone. Probably
      only patients with childhood-onset, isolated GHD (frequently hypothalamic
      dependent) could benefit from treatment with GHRH or growth hormone secretagogues
      (GHS). Whenever restoration of the activity of the GH/insulin-like growth factor
      1 (IGF-1) axis in the elderly would be of use, GHRH and/or GH secretagogues would
      be good candidates. In fact, the existence of a considerable pool of releasable
      growth hormone has been demonstrated in the elderly.

PMID- 10083902
TI  - Defining glaucoma, defining disease: the 1998 Dohlman Lecture.

PMID- 10083903
TI  - Current options in pterygium management.

PMID- 10083904
TI  - Innovations in keratoprosthesis: proved and unproved.
AB  - Progress in the notoriously slow and difficult field of KPro has gained speed
      during the last decade, and interest among corneal surgeons has been increasing
      slowly. Recent advances aimed at preventing complications and treating early
      complications after KPro surgery have improved the prognosis. In retrospect,
      several factors have proved critical to this progress. Organic chemistry has
      given us PMMA--an invaluable material--watery clear and inert. This material may
      be surpassed in the future, but it has served us well during the last half
      century. KPro designs are undoubtedly important, although their role probably has
      been overstated. Temporary postoperative tissue coverage has proved its value.
      Antiinflammatory substances are absolutely vital, and enzyme inhibitors show
      promise. Glaucoma shunts are definitely effective in preventing glaucoma in some
      (but not all) patients. Finally, frequent follow-ups--more than after most other
      ocular surgeries--and early repairs of complications are mandatory. With recent
      resurgence in interest and further developments, the future of KPro surgery
      should be bright.

PMID- 10083905
TI  - Laser in situ keratomileusis for the treatment of myopia.

PMID- 10083906
TI  - Phakic intraocular lenses for correction of high myopia.

PMID- 10083907
TI  - Management of open globe injuries.

PMID- 10083908
TI  - Limbal stem-cell transplantation.

PMID- 10083909
TI  - A step-wise approach to ocular surface rehabilitation in patients with ocular
      inflammatory disease.

PMID- 10083910
TI  - Scleral patch graft in the management of necrotizing scleritis.
AB  - NS is a rare but devastating consequence of certain connective tissue disorders,
      most commonly RA. The presence of NS mandates that patients be treated with at
      least one immunosuppressive chemotherapeutic drug. The cure rate is high in such
      instances after 1 year of freedom from any evidence of recurrent inflammation.
      Surgical treatment through tectonic scleral and peripheral corneal grafting is
      rarely (although sometimes) indicated, except in instances of NS that has
      advanced to the point of perforation of the globe. Various graft materials can be
      used, including fascia lata, periosteum, split-thickness dermis, Gore-Tex
      (synthetic), aortic tissue, and autologous or homologous sclera. Surgical
      treatment alone will not solve the problem for the patient. The physician also
      must control the underlying immunoregulatory dysfunction that has caused the
      destruction initially to protect the graft and, subsequently, the patient's eye.

PMID- 10083911
TI  - Long-term evaluation of initial filtration surgery.

PMID- 10083912
TI  - Advances in aqueous shunting procedures.

PMID- 10083913
TI  - Ahmed valve and uveitic glaucoma.

PMID- 10083914
TI  - Diode laser transscleral cyclophotocoagulation.

PMID- 10083915
TI  - Endocanalicular Nd: YAG laser dacryocystorhinostomy.

PMID- 10083916
TI  - Treatment of traumatic optic neuropathy.

PMID- 10083917
TI  - Frozen-section diagnosis in ophthalmic surgery.

PMID- 10083918
TI  - Biopsy of the retina and the choroid.

PMID- 10083919
TI  - Diagnostic vitrectomy and uveitis.
AB  - When properly used, diagnostic vitrectomy can be an extremely helpful procedure
      for establishing the etiology of ocular inflammation. New instruments have
      enabled more expedient and safer surgery. Analytical assays continue to improve
      in quality and quantity as our understanding of ocular diseases grows. Though no
      single assay is completely sensitive, a combination of assays may improve the
      yield and accuracy of diagnostic vitreous biopsy (Table 5). Keeping abreast of
      these advances may aid ophthalmologists in obtaining earlier diagnosis and better
      outcomes for their patients.

PMID- 10083920
TI  - Ophthalmic endoscopy: applications in intraocular surgery.

PMID- 10083921
TI  - Surgical approaches for the removal of posteriorly dislocated crystalline lenses.

PMID- 10083922
TI  - Surgical management of macular hole.

PMID- 10083923
TI  - Surgical advances in retinopathy of prematurity.

PMID- 10083924
TI  - Surgical management of subretinal hemorrhage.

PMID- 10083925
TI  - Surgical management of choroidal neovascular membranes.

PMID- 10083926
TI  - Laparoscopy and hysteroscopy.
AB  - This article serves as a general review of laparoscopy and hysteroscopy. Subjects
      covered include equipment and instrumentation, use of laser and electrosurgery,
      surgical technique, and complications.

PMID- 10083927
TI  - Complications of laparoscopy. Strategies for prevention and cure.
AB  - With a detailed knowledge of pelvic anatomy, familiarity with the many
      laparoscopic instruments, and attention to the details of good technique, many of
      the complications of laparoscopy described in this article can be avoided. The
      information presented complements that in the other articles in this issue and
      briefly summarizes many salient lessons already published in other excellent
      texts. The focus is on the most common laparoscopic complications, namely, those
      associated with insufflation and trocar insertion, such as vascular injury and
      bowel perforation. Other complications that may arise during adhesiolysis,
      removal of and bleeding from an ectopic pregnancy, and specimen removal from the
      abdomen are also discussed.

PMID- 10083928
TI  - Complications of hysteroscopy.
AB  - Most of the complications of hysteroscopy are avoidable and, fortunately, rare.
      With improved training, experience, and technology, most of these complications
      should become extinct. There will always be some unavoidable complications as
      well as difficulties resulting from inexperience. A goal for the future is to
      teach operating room personnel how to recognize and treat these complications to
      ensure the best patient outcome possible. Once gynecologic surgeons recognize the
      safety and efficacy of diagnostic and operative hysteroscopy as a minimally
      invasive option to treat benign uterine pathology, these procedures will
      proliferate and result in better patient care and improved quality of life.

PMID- 10083929
TI  - Falloposcopy.
AB  - The role of the human fallopian tube in reproduction is more than a passive
      conduit. This organ is involved in oocyte pick-up, fertilization, and embryo
      transport. Metabolic substrates, cytokines, and immunoglobulins have been
      identified within the tubal lumen. Complex and coordinated endocrine secretions,
      neuromuscular activity, and cilial action are required for successful tubal
      function.

PMID- 10083930
TI  - Ultrasound guidance during endoscopic procedures.
AB  - The use of laparoscopic ultrasound probes has been shown to improve outcomes and
      facilitate surgery for hepatobiliary and pancreatic cancers. It is a useful,
      inexpensive, and safe imaging technique that should also supplement operative
      laparoscopy for gynecologic indications. These techniques are new, and their use
      in gynecologic surgery has not been adequately evaluated to recommend widespread
      use. The principal benefit of ultrasound monitoring during operative laparoscopy
      is its potential impact on operative management and decision making.
      Theoretically, the intentions would be to reduce the amount of tissue dissection,
      for example, by more precisely locating an ovarian endometrioma; to reduce
      operating time; and to monitor more closely intrauterine procedures. Further
      prospective randomized studies are needed to define the exact role of ultrasound
      monitoring in gynecologic surgery. An exciting possibility is its use to define
      intraovarian anatomy more definitively in the hope of minimizing the amount of
      ovarian dissection and, in select circumstances, guiding further intrauterine
      surgery. With the use of steerable probes, an assessment could be made of the
      pelvic side wall in oncologic surgery to select specifically nodes that are
      highly suspicious for malignancies, thereby minimizing the amount of dissection
      necessary in staging procedures. Intraoperative ultrasound guidance in
      intrauterine endoscopic procedures offers a noninvasive means of assessing the
      precision of such procedures and provides information regarding the exact
      location of instruments within the uterine cavity and uterine wall. It has been
      used for almost 15 years, and adequate clinical experience has been accrued. It
      offers an alternative to more invasive laparoscopy and may be considered as an
      adjunct to any complicated intrauterine procedure.

PMID- 10083931
TI  - Laparoscopic tubal sterilization. Methods, effectiveness, and sequelae.
AB  - The following statements summarize the material presented herein. 1. Although
      laparoscopic tubal ligation remains an effective and widely available form of
      birth control throughout the world, cumulative failure rates may be higher than
      previously reported, and patients should be appropriately counseled, with special
      attention to younger women. 2. Proper surgical technique is important in reducing
      failure rates, particularly with regard to applying clips or using bipolar
      cautery. Teaching institutions should employ strict guidelines for instructing
      residents in the most effective techniques. 3. Although overall rates of ectopic
      pregnancy are lower after tubal ligation (as is true with any form of birth
      control), should pregnancy ensure from a failed procedure, there is a 30% to 80%
      chance of ectopic pregnancy. Consideration should be given to earlier ultrasound
      and documentation of the location of the pregnancy. 4. There is little evidence
      to support PTLS from a biologic standpoint. The data on increased hysterectomies
      in post-tubal patients may be a result of multiple factors, particularly for
      women aged less than 30 years at the time of occlusion. 5. Although the majority
      of women report satisfaction with sterilization, thorough counseling for all
      women cannot be overemphasized. Women aged less than 30 years should be
      completely aware of all alternatives and possibly encouraged to try another
      method prior to permanent sterilization.

PMID- 10083932
TI  - Anesthesia for office endoscopy.
AB  - A trend is emerging in the United States whereby surgical procedures are
      gradually migrating to less complex environments. The demands of cost
      containment, pressures to limit unnecessary time delays, and desires for
      increased control have all conspired to promote ambulatory surgicenters, minor
      procedure center, and office surgical suites. Concomitant with this shift is a
      differing attitude toward anesthesia, with an increasing number of procedures
      using alternatives to general anesthesia, such as regional blocks and conscious
      sedation.

PMID- 10083933
TI  - Office microlaparoscopy under local anesthesia.
AB  - Office laparoscopy under local anesthesia is especially suited to meet the
      current pressures of quality versus cost in an era of managed care. It is likely
      that this technique will soon become a major part of the practicing
      gynecologist's diagnostic operative armamentarium. Advantages of office
      microlaparoscopy under local anesthesia are realized by the practitioner, the
      patient, and the managed care provider. Office microlaparoscopy under local
      anesthesia is a safe, effective, and less costly tool for the evaluation of
      patients with many different indications. To date, the procedure has been
      primarily used for patients with infertility, chronic pelvic pain, and tubal
      ligation. The ease of scheduling, reduced costs, and rapid recovery suggest that
      it may be the preferred initial procedure for these patients.

PMID- 10083934
TI  - Endoscopic treatment for endometriosis.
AB  - Endometriosis is best regarded as a chronic disease that can vary in
      symptomatology over time. Endoscopic therapy for relief of pelvic pain as well as
      infertility is a therapeutic option. The formation of a rational treatment plan
      before surgery will ensure a minimum number of reproductive surgeries over the
      patient's lifetime.

PMID- 10083935
TI  - Endoscopic myomectomy. Laparoscopy and hysteroscopy.
AB  - There is a place for both laparoscopy and laparotomy in the surgical management
      of patients with uterine myoma. The surgeon's expertise in laparoscopic suturing
      is a crucial requirement for laparoscopic myomectomy. Hysteroscopic myomectomy is
      the best treatment of women with submucous myoma.

PMID- 10083936
TI  - Laparoscopic treatment of stress urinary incontinence.
AB  - Patients with severe GSI owing to ISD should be identified before surgery.
      Standard anti-incontinence procedures such as the Burch, M-M-K, and needle
      suspension have unacceptably high failure rates in these cases. Careful patient
      selection for the procedure and tailoring the type of surgery for the patient's
      condition will improve the clinical outcome and reduce failure rates of anti
      incontinence surgery.

PMID- 10083937
TI  - Laparoscopically assisted vaginal hysterectomy.
AB  - The LAVH revolution beginning in the late 1980s is far from over. The
      overwhelming growth and, at times, overuse of the laparoscopic approach have
      waned somewhat as physicians reevaluate LAVH, adopt new techniques such as
      arterial embolization and myolysis, and rediscover old techniques such as uterine
      morcellation at vaginal hysterectomy. In addition, the cost of new procedures and
      instrumentation has come under intense scrutiny. As analysis of patient care
      moves from cost containment to improved outcomes, there will be renewed interest
      in minimally invasive approaches. The challenge to accumulate data, critically
      analyze each approach, and select the most appropriate procedure for each patient
      holds the greatest promise for improved patient satisfaction and outcomes.

PMID- 10083938
TI  - Laparoscopic microsurgical tubal anastomosis.
AB  - The authors explored the feasibility of performing true microsurgery through the
      laparoscope in 1990. The first laparoscopic microsurgical tubal anastomosis was
      performed in February 1992. Operative laparoscopy will continue to expand as
      technical feasibility continues to improve, driven by both hardware advances and
      increased surgical dexterity. Laparoscopic microsurgery will introduce a new
      dimension to reproductive surgery and over time, will replace laparotomy for
      microsurgery.

PMID- 10083939
TI  - Gynecologic cancer and laparoscopy.
AB  - Numerous technologic and surgical advances have led to the application of
      operative laparoscopic techniques to gynecologic cancers. Operative laparoscopy
      has been described in the surgical staging and treatment of patients with
      ovarian, cervical, and endometrial cancers. it seems to be a very promising
      approach with the potential to revolutionize numerous aspects of the management
      of gynecologic malignancies. Since 1996, the SGO has offered an operative
      laparoscopy course to all gynecologic oncology fellowship programs. Boike and
      colleagues report that faculty and fellows from 25 different fellowship programs
      have attended the 2-day course. In questionnaires filled out at the completion of
      the course, more than 85% of respondents believed that operative laparoscopic
      procedures were equivalent to open techniques and should be taught in fellowship
      programs. Despite the enthusiasm for the use of endoscopy in patients with
      gynecologic malignancies, its potential is unconfirmed and its hazards unknown.
      Reports regarding complications and long-term results are just now beginning to
      be published. More clinical data must be collected before the minimally invasive
      techniques can be accepted as new surgical standards. Ongoing prospective
      clinical trials will help to answer many of the questions regarding safety and
      efficacy. Pending the completion of additional trials, operative laparoscopy will
      remain a promising but unproven tool in the management of patients with
      gynecologic cancer.

PMID- 10083940
TI  - Hysteroscopy in the management of abnormal uterine bleeding.
AB  - The ever-increasing value of diagnostic and operative hysteroscopy for patients
      with AUB serves as an appropriate, although belated, tribute to Pantaleoni who in
      1869 dared to look inside a woman's uterus. Future generations of women and their
      physicians will be indebted to this physician-pioneer. Contemporary
      instrumentation permits the gynecologist to acquire quickly the basic skills
      necessary for routine performance of office-based hysteroscopy. With increasing
      experience, operative hysteroscopic techniques, including resection of polyps,
      myomata, and endometrial ablation, can be easily mastered.

PMID- 10083941
TI  - Malpractice in psychotherapy. An overview.
AB  - A generation ago, psychotherapy was rarely the subject of a malpractice suit.
      Most litigation involving psychiatrists resulted from physical harm, rather than
      emotional harm, to the patient. During the last twenty-five years, the situation
      has changed with juries returning verdicts in a large number of cases awarding
      damages totaling millions of dollars. More recently, restrictions on bringing
      medical malpractice claim generally have multiplied, but now the role of managed
      care is affecting the standard of care and choice of treatment.

PMID- 10083942
TI  - Managed care, liability, and ERISA.
AB  - Congress originally passed ERISA to secure the contractual benefits negotiated
      between employers and employees. In 1974, when the statute quickly moved through
      Congress, no one realized what its eventual significance for health care would
      be. Certainly no one expected that ERISA preemption would allow MCHPs to reduce
      professional standards of care while being protected from liability. The
      Department of Labor believes that it was never the intention of Congress to
      preempt ordinary damage claims for malpractice. There are now chinks in the legal
      armor of ERISA created by activists' courts as in the Dukes case. Even
      conservative Judges recognize the injustice of results, such as Corcoran. The
      American medical profession has traditionally complained about malpractice
      litigation and the wastefulness of defensive medicine. Perhaps ERISA will make
      the profession recognize that malpractice liability can serve a useful purpose.

PMID- 10083943
TI  - Therapist-patient sex. From boundary violations to sexual misconduct.
AB  - It is the therapist's ethical, professional, and legal duty to establish and
      maintain treatment boundaries consistent with the provision of good clinical
      care. The therapist must guard against progressive boundary violations that are
      damaging to patient care and that may also lead to sexual exploitation of the
      patient.

PMID- 10083944
TI  - The clinician's duty to protect third parties.
AB  - The jurisprudence on a clinician's duty to protect third parties is complex and
      continues to evolve. Clinicians should familiarize themselves with civil
      commitment laws, privilege and confidentiality statutes, protective disclosure
      statutes, reporting requirements, and the Tarasoff Principle, as they would case
      law in the state in which they practice. Ethical codes and ethical position
      statements provide useful guidance. In their practices, clinicians should
      endeavor to conduct careful assessments for diagnoses, the patient's current
      situation, and dangerousness. Traditional clinical, therapeutic, and
      instructional measures should always be considered first, and reasonable efforts
      should be made to enlist the patient's cooperation. Occasionally, however,
      hospitalization or protective disclosures must be made. The proposed algorithm
      should be of help to the clinician in making critical decisions regarding
      hospitalization and disclosures to protect others. In following this decision
      tree, four questions are of key importance: (1) Is the patient dangerous to
      others?; (2) Is the danger due to serious mental illness?; (3) Is the danger
      imminent?; and (4) Is the danger targeted at identifiable victims? This algorithm
      is intended to assist in the application of, and should not replace, clinical
      judgment.

PMID- 10083945
TI  - Repressed memories. When are they real? How are they false?
AB  - The precise mechanisms by which such false memories are constructed awaits
      further research. Much is left to learn about the degree of confidence and the
      characteristics of false memories created in these ways. We have more to learn
      about the types of individuals who are particularly susceptible to these forms of
      suggestion, and conversely, who is resistant. As we are learning more, it is
      probably important to heed the cautionary tale in the data already obtained;
      mental health professionals, interviewers, and others need to know how much they
      can potentially influence participants in research, clinical, and forensic
      contexts and take care to avoid that influence when it might be harmful. Periodic
      re-reading of Shakespeare's A Midsummer Night's Dream, with a small substitution
      (change "poet" to "therapist" or to "biased interviewer"), might help keep these
      important ideas in mind, reminding us how hard it can sometimes be to distinguish
      a bush from an imagined bear: The poet's eye, in fine fanciful rolling, Doth
      glance from heaven to earth, from earth to heaven; And as imagination bodies
      forth The forms of things unknown, the poet's pen Turns them to shapes and gives
      to airy nothing A local habitation and a name. Such tricks hath strong
      imagination, that if it would but apprehend some joy, it comprehends some bringer
      of that joy; Or in the night, imagining some fear, How easy is a bush supposed a
      bear!

PMID- 10083946
TI  - Juvenile violence.
AB  - No one missing piece can solve the puzzle of juvenile violence. Although numerous
      risk factors have been identified, the implementation of successful preventive
      and treatment programs remains the greatest challenge. With children increasingly
      turning to gangs as substitutes for their families and using weapons to solve
      their problems, there is little alternative but to meet this challenge. The
      consequence of failing to do so is summarized by King's prophetic statement, "The
      choice today is no longer between violence and nonviolence. It's either
      nonviolence or nonexistence."

PMID- 10083947
TI  - Stalking. An old behavior, a new crime.
AB  - Stalking is an old behavior, but a new crime. The author has reviewed what is
      currently known about the epidemiology, demography, psychiatry, psychology,
      pursuits and outcomes, threatening communications, violence, and clinical risk
      management of stalking cases. But this "dark heart of romantic pursuit" (p 7)
      extends beyond the paradigm of science and is often an aggressive and aberrant
      expression of unrequited love. In 1579, John Lyly wrote "As the best wine doth
      make the sharpest vinegar, so the deepest love turneth to the deadliest hate"
      (Euphues: The Anatomy of Wit).

PMID- 10083948
TI  - The clinician's role in assessing workplace violence.
AB  - Workplace violence can be an area of consultation for psychiatrists. However, the
      clinician must understand not only the limits of violence prediction, but also
      the corporate culture in which he or she will become involved. Evaluation of
      threats may involve review of written notes or taped recordings; the employee may
      or may not be seen. Corporate consultations sometime involve a split allegiance
      on the part of the clinician who must both advise the company and render a
      decision about the employee. The dynamics of violence within the workplace are
      discussed.

PMID- 10083949
TI  - Sexual predators.
AB  - Social responses to sex-offending behaviors have included criminal sanctions and
      clinical interventions that have evolved over time. These developments have
      created various challenges for mental health professionals charged with providing
      care to offenders, particularly when legislative expectations have exceeded
      available treatments. A summary is provided of recent clinical developments in
      assessments, therapies, and pharmacology. The usefulness of SRIs, in particular,
      may prompt the involvement of more psychiatrists in this treatment. Other
      implications for future practice of these clinical and legal developments are
      also discussed.

PMID- 10083950
TI  - Forensic aspects of sexual harassment.
AB  - Sexual harassment law presents a complex set of issues not only for lawyers but
      also for psychiatrists in their roles both as evaluators and clinicians. Judge
      Reinhardt of the US Court of Appeals for the 9th Circuit, summed up these
      complexities: "We tend these days, far more than in earlier times, to find our
      friends, lovers, and even mates in the workplace. We ... often discover that our
      interests and values are closer to those of our colleagues or fellow employees
      than to those of people we meet in connection with other activities. In short,
      increased proximity breeds increased volitional sexual activity." On the other
      hand, he notes that Title VII "entitles individuals to a workplace that is free
      from the evil of sexual intimidation or repression. It is frequently difficult to
      reconcile the two competing values." He goes on to ask, "When does a healthy
      constructive interest in romance become sexual harassment? To what extent is
      pursuit of a co-worker proper but of a subordinate forbidden? Is wooing or
      courting a thing of the past? Must a suitor cease his attentions at the first
      sign of disinterest or resistance? Must there be an express agreement before the
      person seeking romance may even hold the hand of the subject of his affection? Is
      it now verboten to steal a kiss? In the workplace? Everywhere? Under all
      circumstances or only some? Has the art of romantic persuasion lost its charm?
      Questions relating to love and sex are among the most difficult for society to
      answer." The US Supreme Court has stressed the need for common sense in
      evaluating cases of sexual harassment. Perhaps psychiatrists can play a sobering
      role in developing answers to these questions.

PMID- 10083951
TI  - Psychiatric disability, employment and the Americans with Disabilities Act.
AB  - Understanding the ADA as it applies to employment is necessary for a psychiatrist
      to be useful in the assessment of disability under the ADA. As more claims are
      brought into the courtroom, the growing body of case law will further elucidate
      the fine points of interpretation of the ADA.

PMID- 10083952
TI  - The detection of malingered psychosis.
AB  - The detection of malingered psychosis is sometimes quite difficult. The decision
      that an individual is malingering is made by assembling all of the clues from a
      thorough evaluation of a person's past and current functioning with corroboration
      from clinical records and other people. Identifying malingered psychosis will
      prevent unnecessary hospital admissions and is critical in forensic assessments.
      Indeed, clinicians bear considerable responsibility to assist society in
      differentiating true psychosis from malingered madness.

PMID- 10083953
TI  - The right to refuse psychiatric treatment.
AB  - The right to refuse psychiatric treatment has become an important clinical and
      legal issue in the last twenty-five years. This article briefly reviews the
      clinical, administrative, and legal aspects of the right to refuse psychiatric
      treatment, especially medication. Emphasis is placed on the clinical issues
      including the reasons for treatment refusals, and the management of treatment
      refusal. Empirical data are provided to illustrate the rights driven and
      treatment driven models of involuntary psychotropic medication administration.

PMID- 10083954
TI  - Coerced treatment in the community.
AB  - Psychiatric patients have always been subjected to coerced treatment or
      management in the community. In the 1970s, civil rights litigation established
      formalized procedures for such coercion. This article discusses the types of
      procedures established and their effectiveness as well as their flaws.
      Suggestions are made to improve the efficacy of existing procedures.

PMID- 10083955
TI  - The United States Supreme Court and psychiatry in the 1990s.
AB  - In the 1990s, the Supreme Court has decided several cases that have had an impact
      on psychiatry and psychiatric patients in the criminal justice system, on
      psychiatric hospitalization, and on psychotherapist-patient privilege. Of the
      seven cases discussed in this article, Chief Justice Rehnquist and Justice Scalia
      voted similarly in all seven cases. Since joining the court, Justice Thomas has
      voted with them. Justice Scalia interprets the Constitution, using what has been
      termed "textualism": avoid reference to legislative history, and interpret the
      Constitution according to the plain language meaning of the relevant section.
      Chief Justice Rehnquist and Justices Scalia and Thomas are inclined to protect
      states' rights from court decisions that expand US Constitutional power in cases
      involving civil plaintiffs and criminal defendants. They seek to protect states
      from being sued in federal courts, and, if there is doubt, lean toward not
      interfering with state prerogatives. They tend to not find unenumerated rights
      and prefer clear-cut rules over amorphous standards. Justices Kennedy and
      O'Connor, at times joined by Justice Souter in the middle of the court, provide
      the deciding votes in many cases. They seem to prefer a case-by-case pragmatism
      over a global jurisprudential philosophy. Approaching cases one at a time, they
      usually avoid broad philosophic pronouncements when they join with Chief Justice
      Rehnquist. Justice Stevens, joined by Justices Breyer and Ginsburg since they
      have been appointed to the court, is more likely to favor a broader reading of
      the 14th Amendment's Due Process and Equal Protection clauses. Of the seven
      cases, Kennedy and O'Connor voted with the majority in five cases, the dissent in
      one case (Zinermon v Burch), and split their votes in one case (Foucha v
      Louisiana, with O'Connor siding with the Court and Kennedy with the dissent).
      Commager, a noted historian, believed that political issues can be explored,
      explained, and debated and that the people of the new American democracy, armed
      with knowledge and freedom to defend, argue, and choose, will make the right
      decisions for their common welfare. This theory applies equally to the court:
      Whenever questions involving psychiatry and psychiatric patients are brought to
      the court, American psychiatry must make its views known in that forum. To do so
      requires awareness and knowledge of the cases that involve psychiatry and
      psychiatric patients that the court has decided, including those decided in the
      1990s. To participate effectively, psychiatrists must understand the political
      landscape in which the cases arrive at the court's doorstep and the composition
      and leanings of the court and examine carefully the fact patterns (understanding
      that some fact patterns are more sympathetic than others). This awareness should
      result in amicus briefs that are scholarly, rely on empiric data, and are
      scrupulously honest about the limitations of our knowledge. In this way,
      psychiatrists may fully participate in the debate and aid the court in its
      exploration and analysis of the issues involving psychiatry and psychiatric
      patients.

PMID- 10083956
TI  - Central modulation of pain perception.
AB  - The information presented in this article provides a basis for individual
      variability in the sensation of pain and the behavioral correlates associated
      with pain. The knowledge of pain-inhibitory and pain-facilitating pathways linked
      to cognitive, emotional, and stress-response systems leads to a greater
      understanding of the complexities of the experience of pain. Appreciation of the
      influence of these higher centers should lead to improvements in the clinical
      management of pain.

PMID- 10083957
TI  - Pain in the rheumatic diseases. Practical aspects of diagnosis and treatment.
AB  - Patients with rheumatic disease experience pain that can be intense, persistent,
      and disabling. This pain is frequently multifactorial in origin and has both
      central and peripheral components. Because of the array of conditions that can
      cause musculoskeletal pain, patient management must begin with a complete
      clinical assessment that identifies possible etiologies and measures objective
      findings against subjective complaints. Especially in patients with known
      rheumatic disease, the possibility of concurrent pain of central origin must be
      considered and appropriate treatment given. By applying a comprehensive therapy
      plan of drugs, physical therapy, and patient education, significant benefits can
      often be achieved in this prevalent group of painful diseases.

PMID- 10083958
TI  - Causes of pain in children with arthritis.
AB  - Pain in children with juvenile rheumatoid arthritis (JRA) is often not fully
      recognized and is therefore incompletely treated. The use of pain assessment
      instruments developed specifically for children may enhance recognition by health
      care providers. Recent studies suggest that coping variables and disease severity
      are significant predictors of pain in children with JRA. Pain in children with
      JRA is a complex phenomenon, best managed using a multidisciplinary approach that
      includes aggressive traditional medical management and addresses psychosocial
      variables such as coping strategies and perceptions about disease.

PMID- 10083959
TI  - Pain in fibromyalgia.
AB  - Just as our caveman forebears were frail in the face of predatory animals, we are
      frail in today's society of childhood neglect or abuse, bumper-to-bumper traffic,
      frustration at work, and multiple daily hassles. The same neuroendocrine systems
      and pain regulatory mechanisms that protected early man during acute stress are
      still encoded in our genome, but may be maladaptive in psychologically and
      physiologically vulnerable people faced with chronic stress. Many patients with
      fibromyalgia become vulnerable because of the long-lasting psychological and
      neurophysiological effects of negative experiences in childhood. Ill-equipped
      with positive cognitive, emotional, and behavioral skills as adults, they display
      maladaptive coping strategies, low self-efficacy, and negative mood when
      confronted with the inevitable stressors of life. Psychological distress ensues,
      which reduces thresholds for pain perception and tolerance (already relatively
      low in women) even further. Converging lines of psychological and neurobiological
      evidence strongly suggest that chronic stress-related blunting of the HPA,
      sympathetic, and other axes of the stress response together with associated
      alterations in pain regulatory mechanisms may finally explain the pain and
      fatigue of fibromyalgia. Vulnerable people who can be classified by the ACR
      criteria as having fibromyalgia do not have a discrete disease. They are simply
      the most ill in a continuum of distress, chronic pain, and painful tender points
      in the general population.

PMID- 10083960
TI  - Psychosocial assessment of pain in patients having rheumatic diseases.
AB  - A variety of reliable and valid psychosocial assessment instruments have been
      developed. Many of these instruments are brief and easily incorporated into
      clinical practice settings. Measures of coping, self-efficacy, helplessness, and
      cognitive distortion are especially useful in understanding the pain experience
      in rheumatic disease populations. Information gleaned from psychosocial
      assessments is increasingly being used to guide pain treatment efforts. Recent
      research, suggests that treatment outcomes can be improved if one tailors
      psychosocial pain management protocols to address the particular problems
      identified by comprehensive psychosocial assessments. Considered overall,
      psychosocial assessment methods have much to offer the clinician working with
      patients having persistent pain. The current status of this field is promising,
      and as psychosocial assessment methods become even more fully integrated into
      clinical practice, they are likely to yield even greater insights into the pain
      experience of patients with rheumatic diseases.

PMID- 10083961
TI  - Negative affect and pain in arthritis.
AB  - The experience of pain in arthritis conditions has important affective
      dimensions. This article reviews evidence for a relatively strong association
      between negative affect (i.e., depression, anxiety, and anger) and arthritis
      related pain. Possible physiologic and psychologic mechanisms of the relationship
      between negative affect and pain are examined, and issues relevant to future
      research, particularly the need for biopsychosocial theoretical models are
      discussed. Finally, the article highlights the importance of biopsychosocial
      treatment approaches in managing arthritis-related pain and negative affect.

PMID- 10083962
TI  - The contribution of functional imaging techniques to our understanding of
      rheumatic pain.
AB  - The main cerebral components of the human pain matrix have been defined using
      functional imaging techniques. The experience of pain is likely to be elaborated
      as a result of parallel processing within this matrix. There is not, therefore, a
      single pain center. The determinants of pain are as likely to be determined by
      top-down as by bottom-up processes. The precise function of the different
      components of the matrix are just beginning to be defined. There appear to be
      important adaptive responses in the forebrain components of the matrix during
      arthritic pain. Endogenous opioid peptides are strong candidates for the
      modulation of some of these responses. More extensive and sequential behavioral
      and functional imaging studies are required to establish the contribution these
      adaptive responses make to the perception of pain.

PMID- 10083963
TI  - The use of analgesics in the management of pain in rheumatic diseases.
AB  - Pain is the most common complaint of patients who see rheumatologists. In this
      article, the current treatment options for pain are reviewed; these include
      acetaminophen, nonsteroidal anti-inflammatory drugs, new specific cyclooxygenase
      2 inhibitors, opioid analgesics, centrally acting muscle relaxants,
      antidepressants, and topical analgesics and counterirritants. The doses of
      medication and known adverse effects of these medications are highlighted.

PMID- 10083964
TI  - Aggressive pharmacologic treatment of pain.
AB  - In this article, the author outlines the pharmacology of nociception and
      discusses the two major classes of drugs used for pain control: opioids and
      nonopioid analgesics. In order to provide satisfactory pain relief and prevent
      the possible sequelae of untreated pain, physicians must possess both knowledge
      and expertise in the use of opioid and nonopioid analgesics. Opioid analgesics
      have been underused in the management of pain. Opioids have a higher analgesic
      potency and wider range of indications than any of the other currently available
      medications for pain control. The second class of drugs, the nonopioid analgesics
      and adjuvants, has recently expanded to include new and potentially beneficial
      medications. This article furthers the understanding on how to use analgesics for
      a prompt, safe, and effective pharmacologic treatment of acute and chronic pain.

PMID- 10083965
TI  - Psychological and behavioral approaches to pain management for patients with
      rheumatic disease.
AB  - This article reviews the efficacy of the psychological and behavioral pain
      management interventions that have been evaluated among adult patients with
      rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Using
      published criteria for empirically validated interventions, it is concluded that
      cognitive-behavioral therapies and the Arthritis Self-Management Program
      represent well-established treatments for pain among patients with RA and OA.
      These interventions involve education, training in relaxation and other coping
      skills, and rehearsal of these skills in patients' home and work environments.
      There currently are no psychological or behavioral interventions for pain among
      FM patients that can be considered as well-established treatments. Future
      intervention research should use clinically meaningful change measures in
      addition to conventional tests of statistical significance, attend to the pain
      management needs of children, and assess whether outcomes produced in university
      based treatment centers generalize to those in local treatment settings.

PMID- 10083966
TI  - The role of physical therapy and physical modalities in pain management.
AB  - This article provides an overview to arthritis care of the common physical
      modalities (heat, cold, transcutaneous electrical nerve stimulation, low-energy
      laser, topical applications, and external devices). The rationale for use and
      effectiveness of the various physical modalities are discussed. Exercise is
      presented in terms of mode and effect of range of motion, muscle conditioning,
      and aerobic exercise.

PMID- 10083967
TI  - J. H. Louw Memorial Lecture. Brothers. Delivered at the University of Cape Town,
      29 October 1997.

PMID- 10083968
TI  - Congenital alimentary tract abnormalities presenting in adolescence and young
      adulthood.
AB  - Intestinal atresias and duplications of the alimentary tract commonly present in
      the neonatal period or early infancy, but in rare cases they can persist and
      present de novo during adolescence. We report on these two abdominal congenital
      anomalies, the clinical presentations of which in adolescence and young adulthood
      are unique.

PMID- 10083969
TI  - Blunt cardiac rupture.
AB  - Cardiac rupture as a result of blunt trauma is not commonly encountered. Seven
      patients with this injury have been treated at Groote Schuur Hospital over the
      past 14 years. All presented with cardiovascular collapse and 4 developed signs
      of cardiac tamponade. A clinical diagnosis was made in 4 patients and
      echocardiography was done in 3. Pericardiocentesis was used in 1 patient to
      confirm the diagnosis. Significant diagnostic delay occurred in 1 patient with
      associated liver rupture. Two patients required emergency room thoracotomy. All
      other patients were approached using a median sternotomy. Five patients survived,
      giving an overall survival rate of 71%. Five patients had right atrial ruptures
      and 2 right ventricular ruptures. One patient with right ventricular rupture died
      in the operating room, while another patient with multiple right atrial ruptures
      died from multiple organ failure after 11 days. We also briefly review the
      history, mechanisms and pathology.

PMID- 10083970
TI  - Patterns of injury and white cell response in critically ill trauma patients who
      present with leucopenia.
AB  - The outcome of critically ill trauma patients who presented to the intensive care
      unit with leucopenia (total peripheral white cell count < 4 x 10(9)/1) was
      studied prospectively with respect to the total white cell and neutrophil
      response. A total of 105 patients, of whom 30 were leucopenic, were admitted to
      the ICU during a 4-month period. The prevalence of leucopenia was significantly
      higher in patients with gunshot wounds (P < 0.05) and hollow visceral intra
      abdominal injury (P < 0.001). Eight (27%) of the leucopenic patients died. No
      significant difference was found in initial mean total white cell or neutrophil
      count, or in the differential percentages, between survivors and non-survivors.
      The total peripheral white cell count increased significantly in survivors
      compared with non-survivors (P < 0.001), and significant differences were found
      in absolute neutrophil counts and differential percentages by days 5 and 10
      (counts P = 0.01, P < 0.02; differentials P < 0.01, P < 0.01). These results
      suggest that granulocyte colony-stimulating factor may have a role in the
      treatment of trauma patients with persistent neutropenia following intra
      abdominal hollow visceral injury.

PMID- 10083971
TI  - The burnt male--intentional assault on the male by his partner.
AB  - There are few studies which address the burnt male patient who has been
      intentionally assaulted by his partner. Thirty such patients were admitted to the
      Somerset Hospital Burns Unit between January 1993 and May 1995. The average age
      was 37 years and the mean total burn surface area was 19.6% (range 2-55%). A
      variety of agents had been used to inflict the burn, but throwing hot fluid at
      the victim was the most common. The head, neck and chest were the most common
      areas burnt. Five patients developed respiratory burns and 2 required ventilatory
      support. Three patients died: 1 of respiratory failure and 1 of septicaemia,
      while 1 committed suicide. The burnt and battered male patient is a real clinical
      entity which is becoming more common. Treatment should investigate psychosocial
      factors in addition to ensuring healing of the burn wound.

PMID- 10083972
TI  - Tonsillectomy and the value of peritonsillar infiltrations.
AB  - In this prospective double-blind trial, the effect of peritonsillar infiltrations
      was assessed with regard to intra-operative bleeding and postoperative pain in
      100 young adults who underwent elective tonsillectomy under balanced general
      anaesthesia. Patients were randomly assigned to 1 of 5 groups (20 patients in
      each group) and received infiltrations as follows: group 1--bupivacaine (0.5%)
      with adrenaline (1:200,000); group II--bupivacaine (0.5%); group III--normal
      saline with adrenaline (1:200,000); group IV--normal saline; group V--no
      infiltration (control group). With regard to blood loss, groups I-IV lost a mean
      of 47 ml (95% CI = 69.78), while group V lost a mean of 121 ml (95% CI = 78.10)
      (P = 0.0002). Group V had the highest pain score (average 4.62) measured in
      recovery, 4 and 24 hours after tonsillectomy (P = 0.0051) and required more
      narcotic analgesia. Groups II and III had the lowest score (average 1.72) after
      24 hours. The bupivacaine group (II) had the highest incidence (71.4%) of nausea
      and vomiting. Peritonsillar infiltrations decrease intra-operative bleeding and
      pain, independent of the type of solution infiltrated, by providing a better
      defined plane of dissection which minimises trauma to the surrounding tissue.
      Normal saline infiltrations with or without adrenaline should be used since they
      have no side-effects and are inexpensive and easily available.

PMID- 10083973
TI  - Renal tuberculous abscess masquerading as a liver mass.

PMID- 10083974
TI  - Design, anticonvulsive and neurotoxic properties of retrobenzamides. N
      (Nitrophenyl)benzamides and N-(aminophenyl)benzamides.
AB  - Design, anticonvulsant properties in maximal electroshock-induced seizures [MES]
      and seizures induced by subcutaneous administration of pentetrazole (scPtz), and
      neurotoxicity of retrobenzamides (N-(nitrophenyl)benzamides and N-(aminophenyl)
      benzamides are reported. These data are further compared with those on
      carbamazepine, phenytoin, ameltolide and other reference compounds. Studies on
      retrobenzamides in mice dosed intraperitoneally point out a good anticonvulsant
      potential in the MES test for the amino derivatives (N-(aminophenyl)benzamides)
      and moderate activity for corresponding "nitro" derivatives. In rats dosed
      orally, aminoretrobenzamides were, however, less active in the MES test than in
      mice dosed intraperitoneally. Differences between experimental animal species and
      administration routes lead to hypothesize rapid metabolization of compounds,
      reduced intestinal resorption and increased removal from body. The presence of a
      methyl substitution on the N-phenyl moiety of aminoretrobenzamides attenuated
      these discrepancies between mice and rats. Present results indicate that
      pharmacological values--including the dose offering anticonvulsant protection in
      50% of tested animals (ED50) and protective indices--obtained on some
      retrobenzamides may compete with phenytoin and carbamazepine values. By contrast
      with phenytoin, some retrobenzamides further exhibit activity in the scPtz test.

PMID- 10083975
TI  - Molecular and neurochemical evaluation of the effects of etizolam on GABAA
      receptors under normal and stress conditions.
AB  - The thienobenzodiazepine derivative etizolam (CAS 40054-69-1, 6-(o-chlorophenyl)
      8-ethyl-1-methyl-4H-s-triazolo-(3,4-c)thienol(1 ,4) diazepine) is a potent
      anxiolytic with a pharmacological profile similar to that of classical
      benzodiazepines. In order to rationalize the therapeutic use of etizolam, its
      pharmacodynamics properties on GABAA receptors were investigated by a comparative
      study with other ligands on human recombinant GABAA as well as rat brain native
      receptors. Etizolam inhibited in a concentration-dependent manner
      [3H]flunitrazepam (CAS 1622-62-4) binding to rat cortical membranes, with an
      affinity of 4.5 nmol/l greater than that of alprazolam (CAS 28981-97-7) (7.9
      nmol/l). Ethizolam enhanced GABA-induced Cl- currents in oocytes expressing human
      cloned GABAA receptors. With alpha 1 beta 2 gamma 2S subunit combination,
      etizolam produced a 73% increase in GABA-induced currents with an EC50 of 92
      nmol/l. At the same receptor type, alprazolam showed a higher degree of
      potentiation and potency (98%, EC50 56 nmol/l). At alpha 2 beta 2 gamma 2S or
      alpha 3 beta 2 gamma 2S subunit constructs, the effects of etizolam were similar
      to those of alprazolam. Flumazenil (CAS 78755-81-4) completely blocked both
      etizolam and alprazolam effects on GABA-induced currents. Etizolam, administered
      i.p., was uneffective in changing ex vivo t-[35S]butylbicyclophosphorothionate
      ([35S]-TBPS) binding to rat cerebral cortex, whereas alprazolam and abecarnil
      (CAS 111841-85-1) significantly reduced this parameter. However, etizolam
      similarly to abecarnil and alprazolam, antagonized isoniazid-induced increase
      (61%) in [35S]-TBPS binding to rat cortical membranes. Further, etizolam
      inhibited in a dose-dependent manner basal acetylcholine release from both
      hippocampus and prefrontal cortex, and reversed foot-shock-induced increase of
      basal acetylcholine release to a control level. Altogether, these results suggest
      that etizolam may have a reduced intrinsic activity, at least at specific
      subpopulations of GABAA receptors. This property, together with the
      pharmacokinetic indication of a short-acting drug, may characterize etizolam as a
      ligand endowed with less side-effects typical of full agonits such as diazepam
      (CAS 439-14-5) and alprazolam. Finally, given its marked efficacy under
      conditions of GABAergic deficit, etizolam may represent a possible drug of choice
      with reduced liability to produce tolerance and dependence after long-term
      treatment of anxiety and stress syndromes.

PMID- 10083976
TI  - Synthesis and pharmacological evaluation of new (indol-3-yl)alkylamides and
      alkylamines acting as potential serotonin uptake inhibitors.
AB  - A series of new indolylalkylamides 3-18 and alkylamines 19-26 has been prepared
      in the search of novel 5-hydroxytryptamine (5-HT) uptake inhibitors. Synthesis of
      N-2,3 or 4-pyridinyl-(indol-3-yl) acetamides and propionamides 3-10 was achieved
      starting from the corresponding Ph3P/BrCCl3 or DCC-activated acids. Reduction of
      the pyridine nucleus led to the N-piperidinylalkylamides 15-18 via the
      tetrahydropyridinyl derivatives 11-14, and LiAlH4 reduction afforded the desired
      amines 19-26. The affinity of these compounds for 5-HT and also dopamine (DA) and
      noradrenaline (NA) uptake sites was measured. Among the 16 studied amides only N
      (methylpiperidin-3-yl)-(indol-3-yl) propionamide 16 exhibited a moderate 5-HT
      uptake inhibitory effect: 38% at 10 mu mol/l. In contrast the N-pyridinyl-(indol
      3-yl)alkylamines 19-26 exerted high inhibition at this concentration and two of
      them, 23 and 24, remained very efficient at 0.1 mu mol/l. Optimal activity was
      observed in the 4-pyridinyl subseries and was compatible with variation (n = 1,
      2) of the length of the interspacing alkylamino chain. Although 23 and 24 were
      about 17-fold less active than indalpine as 5-HT uptake inhibitors, they
      demonstrated, like indalpine, excellent selectivity for the 5-HT uptake site
      versus the DA uptake site. Both amines inhibited tetrabenazine-induced
      hypothermia and potentiated 5-HTP-induced behavioural effects in mice. The
      absence of 3,4-dioxyphenylalanine (dopa)-induced behavioural effects with
      compound 24 suggests possible antidepressant activity through selective
      inhibition of central neuronal serotonin uptake and/or increased monoamine
      release.

PMID- 10083977
TI  - Biochemical activities of extracts from Hypericum perforatum L. 1st
      Communication: inhibition of dopamine-beta-hydroxylase.
AB  - Extracts from the herb "St. John's wort" (Hypericum perforatum L.) are used for
      the treatment of mental depression, nervousness, sleeplessness and for their
      wound healing, diuretic and antirheumatic properties. As one biochemical
      mechanism for depression lack of catecholamine neurotransmitters has been
      discussed. The results of this investigation show that alcoholic extracts from
      Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine
      beta-hydroxylase with an IC50 of 0.1 mu mol/l; pure commercial hypericin inhibits
      with an IC50 of 21 mu mol/l. Enzymes involved in the synthesis of dopamine from
      tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by
      hypericin at concentrations from 1 up to 10 mu mol/l.

PMID- 10083978
TI  - Biochemical activities of extracts from Hypericum perforatum L. 2nd
      Communication: inhibition of metenkephaline- and tyrosine-dimerization.
AB  - Extracts from the herb "St. John's wort" (Hypericum perforatum L.), besides other
      activities such as wound healing, antigout, antirheumatic and diuretic
      properties, are widely used to counteract neurological disorders such as
      depressive situations, nervousness and sleeplessness. The characteristic and
      leading component in these extracts, the dianthraquinone hypericin, is very
      likely not to represent the main active principle mediating the desirable
      effects. Thus, standardization of the drug is no longer based on the
      quantification of total hypericin and since several years simply the
      determination of dry matter content is in use instead. As biochemical background
      of depression the lack of catecholamine neurotransmitters or decreased beta
      endorphins such as methionine- or leucine-enkephalins have to be envisaged. This
      communication reports on the inhibition of myeloperoxidase-catalyzed dimerization
      of enkephalins by Hypericum extracts. The substitution for enkephalins by
      tyrosine and for myeloperoxidase by horseradish peroxidase may represent a simple
      and inexpensive biochemical model reaction of pathological events during the
      manifestation of depressive events suitable for drug standardization.

PMID- 10083979
TI  - Biochemical activities of extracts from Hypericum perforatum L. 3rd
      Communication: modulation of peroxidase activity as a simple method for
      standardization.
AB  - Alcoholic extracts from the herb "St. John's wort" (Hypericum perforatum L.) are
      widely used to counteract depressive situations, where the question on the mainly
      active principle is still under discussion. Thus, standardization of the drug on
      the basis of dry matter has been chosen instead of the popular leading component,
      hypericin. Inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by
      Hypericum extracts has recently been reported. This method is based on the
      separation and quantification of enkephalin dimers by HPLC. In order to simplify
      this assay myeloperoxidase could be substituted by the cheaper horseradish
      peroxidase and the enkephalins by the amino acid tyrosine without loss of
      significance. In this communication we represent a more rapid photometric method
      based on peroxidase-catalyzed indole acetic acid oxidation suitable for quick,
      simple and economic drug standardization.

PMID- 10083980
TI  - Biochemical activities of extracts from Hypericum perforatum L. 4th
      Communication: influence of different cultivation methods.
AB  - Extracts from the herb "St. John's wort" (Hypericum perforatum L.), know since
      ancient times as medical plant, besides other activities such as wound healing,
      antighout, antirheumatic and diuretic properties, is used in the treatment of
      mild to moderate depression. Increasing application continuously makes
      cultivation under controlled conditions of Hypericum perforatum L. more
      important. This report shows the results of three-years cultivation experiments
      with Hypericum perforatum L. The findings indicate that N-fertilizing yields more
      plant material but results in a drug with less quantity of secondary metabolites.
      Important components of the drug were quantified by HPLC and their activities
      were analyzed with the aid of biochemical test systems. Narrowleaved and
      broadleaved varieties of Hypericum perforatum L. show differences both in
      activity and quality. In this experiments the most active extract was a
      methanolic extract derived from non-fertilized, broadleaved plants.

PMID- 10083981
TI  - Studies on the toxicological profile of the local anaesthetic articaine.
AB  - The toxicity of articaine (CAS 23964-58-1) and of a respective preparation
      (Septanest SP; 4% articaine HCl and epinephrine 1: 100,000) was examined in in
      vitro and in vivo experiments. The following endpoints were examined: repeated
      dose toxicity, reproduction toxicity, mutagenic potential and local tolerance.
      Repeated s.c. administration of articaine HCl in rats and dogs demonstrated no
      pathomorphological systemic changes even at systemically toxic doses. The no
      effect level (NOEL) was 25 mg articaine HCl/kg b.w./day s.c. for the rat and 40
      mg articaine HCl/kg b.w./day s.c. for the dog. Reproduction studies were
      performed in rats and rabbits at doses up to more than 10 times the maximum
      recommended human dose of 7 mg articaine HCl/kg b.w. and revealed no evidence of
      harm to the foetus or to other aspects of reproduction, even at doses toxic to
      the parental animals. Four standard in vitro and in vivo mutagenicity studies
      have shown no mutagenic potential up to cytotoxic concentrations or up to the
      maximum tolerated dose level. The local tolerance of articaine HCl was good to
      very good. The preclinical data indicate that articaine HCl does not possess any
      relevant side-effects or gross toxicity and can be considered a safe local
      anaesthetic.

PMID- 10083982
TI  - Oral bioavailability and pharmacokinetics of the new insulin sensitizer DRF-2189
      in Wistar rats.
AB  - The pharmacokinetics of the new insulin sensitizing agent, DRF-2189 ([5-[4-[2-(1
      indolyl) ethoxy]phenyl]methyl]thiazolidine-2,4-dione, CAS 172647-53-9) were
      studied in male Wistar rats following oral doses of 1, 3 and 10 mg/kg as
      suspension in 0.25% carboxymethylcellulose. Drug was extracted from plasma
      samples using a solvent mixture containing ethylacetate and dichloromethane (3:2)
      and analyzed by high-performance liquid chromatography with fluorescence
      detection. DRF-2189 was absorbed slowly, attaining maximum levels at 2-3 h, and
      was eliminated with a half-life (t1/2) of about 3 h. The Cmax and AUC(0-infinity)
      increased linearly (r2 = 0.99) with the dose, while the elimination half-life
      (t1/2) was independent of the dose. An intravenous pharmacokinetic study of DRF
      2189 was carried out in Wistar rats at a dose of 3.0 mg/kg. The pharmacokinetic
      parameters AUC(0-infinity), t1/2, plasma clearance (Cl) and volume of
      distribution (Vd) were found to be 49.52 micrograms x h/ml, 2.99 h, 16.31 ml/h
      and 45.11 ml. respectively. Oral bioavailability (f) of DRF-2189 in Wistar rats
      was 44%. Based on pharmacokinetic studies, DRF-2189 is a good choice for further
      development.

PMID- 10083983
TI  - Synthesis and antinociceptive activity of some novel nonpeptide derivatives of
      interleukin-1 beta (193-195) sequence.
AB  - The synthesis of a new series of nonpeptide derivatives of interleukin-1 beta
      sequence is described. Compounds have been investigated for their relative
      activity regarding antinociception and suppression of inflammation. Several
      compounds with R1(R)Lys [CH2N]-Pro structure showed better efficacy in the
      inflamed paw pressure test than indometacin and morphine. In terms of the
      relative potencies the above mentioned products (i.e. compounds 2, 4, 5, 6; ED50
      values of 0.002, 0.0035, 0.0032, 0.0074 mg/kg i.p. respectively) were 10-100
      times more potent than indometacin and morphine (ED50 values of 0.22 and 0.75
      mg/kg). Compounds 1-14 were not able to inhibit binding of labeled interleukin-1
      beta to EL 4-6.1 murine cells, since they had no affinity for interleukin-1 beta
      receptors. The antinociceptive activity elicited by compound 4 in the rat
      inflamed paw pressure test was inhibited by naloxone, but the compound was
      inactive in the mouse hot plate and rat paw pressure tests. These results suggest
      that compound 4 exerts its antinociceptive activity through a mechanism which is
      based on the local release of endogenous opioids in injured tissue.

PMID- 10083984
TI  - Synthesis and antileishmanial activity of alpha-cyano ethyl propenoates--a new
      class of antileishmanials.
AB  - A number of alpha-cyano-beta-substituted ethyl propenoates were synthesised by
      condensation of appropriate aldehydes with ethyl cyanoacetate in basic medium.
      These compounds have been studied for their antileishmanial activities in vivo in
      hamsters. Two compounds exhibited 70-77% activities both by intramuscular and
      oral routes.

PMID- 10083986
TI  - Therapeutic effects of LK 423, a phthalimido-desmuramyl-dipeptide compound, on
      dextran sulfate sodium-induced colitis in rodents through restoring their
      interleukin-10 producing capacity.
AB  - A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-glutamic
      acid (CAS 142489-47-2, LK 423), was examined for its possible activity to
      modulate levels and species of cytokines in mice carrying a specific inflamed
      organ. Colonic inflammation was induced in mice by giving 5% dextran sulfate
      sodium (DSS) solution as drinking water. The capacity of spleen cells obtained
      from the DSS-inflamed mice to produce interleukin-10 (IL-10) in response to
      mitogen was significantly reduced when compared with the capacity of spleen cells
      from intact mice. Treatment of the mice administered DSS by subcutaneous multiple
      injections with a low dose of LK423 resulted in delaying the progression to full
      blown inflammation in the colon. The mitogen-stimulated spleen cells obtained
      from the LK423-treated mice yielded significantly greater amounts of IL-10 and IL
      6 than the untreated DSS group, and the peritoneal cells from the LK423-treated
      mice produced significantly lower levels of tumor necrosis factor alpha (TNF
      alpha). Based on this prophylactic effect of LK423 in the murine colitis model,
      its therapeutic effect was examined in rats in which colitis had been induced by
      feeding 3% DSS for 12 days. Intracolonic administration of LK423 to these rats
      for 7 days resulted in diminishing the ulcerative area in the colon. The
      immunological characteristics of this new compound are discussed from the point
      of view of its possible application as a therapeutic agent for inflammatory bowel
      diseases (IBD) and other inflammatory diseases.

PMID- 10083987
TI  - Complete airway obstruction.

PMID- 10083988
TI  - Evidence-based medicine and clinical guidelines: past, present and future.

PMID- 10083989
TI  - Audit of ketoprofen prescribing after orthopedic and general surgery.
AB  - PURPOSE: In 1994, we developed a practice guideline which stated that ketoprofen
      should be used in every adult patient after surgical procedures for which at
      least moderate pain was anticipated. The dose recommended was 50 mg every six
      hours i.v. in the operating room followed by oral administration as soon as
      possible for three days. The purpose of this study was to evaluate the success of
      the guideline implementation. METHODS: In 1995, an audit performed by a research
      pharmacist assistant under the supervision of the authors analysed prospectively
      the files of patients scheduled for orthopedic or general surgery during a one
      month period. The compliance of the nurses was also recorded. RESULTS: Of 185
      patients operated upon during the period, seven were transferred to the ICU and
      were not evaluated. Ketoprofen was not prescribed to 112 (63%) of the 177
      remaining patients, either because minor pain was expected (n = 55) or because
      one or several contra-indications to its use were detected. In cases where
      ketoprofen was used although theoretically contraindicated (11%), review of the
      medical records and interviews of anesthesiologists showed that prescription was
      guided by a risk/benefit analysis. In 18% of cases, nurses did not administer at
      least one dose of ketoprofen although medical prescription requested regular
      administration. CONCLUSION: Although the use of NSAIDs is still controversial,
      implementation by anesthesiologists of a practice guideline introducing
      ketoprofen for postoperative analgesia was successful and the nursing non
      compliance rate to follow written orders was modest.

PMID- 10083990
TI  - [Severe digestive complications after heart surgery using extracorporeal
      circulation].
AB  - PURPOSE: To determine the incidence, circumstances of occurrence and evolution of
      gastrointestinal complications after cardiac surgery with extracorporeal
      circulation (ECC). METHODS: Retrospective chart study of gastrointestinal
      complications in 6.281 patients undergoing ECC between january 1994 and December
      1997. RESULTS: Sixty patients developed 68 gastrointestinal complications (1%).
      Complications included: upper gastrointestinal bleeding (n = 23), intestinal
      ischemia (n = 19), cholecystitis (n = 7), pancreatitis (n = 6), and paralytic
      ileus (n = 16). The incidence of these complications was low after coronary
      artery (0.4%) or valvular surgery (0.8%) and high after cardiac transplantation
      (6%) and after surgery for acute aortic dissection (9%). Compared with a control
      population, patients with gastrointestinal complication had a higher Parsonnet
      score (29 +/- 15 vs 13 +/- 12 points; P = 0.002), were more frequently operated
      upon as an emergency (40/60, 66% vs 1120/6221, 18%; P = 0.01), underwent ECC of
      longer duration (114 +/- 66 vs 74 +/- 42 min; P = 0.01), and presented more
      frequently with low cardiac output after surgery (45/60, 75% vs 435/6221, 7%; P =
      0.001). The mortality rate after gastrointestinal complications was 52%. The
      major factor associated with mortality was the occurrence of sepsis (OR = 38.7).
      Other factors were: renal failure (OR = 7.9), age > 75 yr (OR = 3.5), mechanical
      ventilation for more than seven days (OR = 2.7), associated cerebral damage (OR =
      3.9). CONCLUSION: Gastrointestinal complications after ECC occur in high risk
      surgical patients. These complications are frequently associated with other
      complications leading to a high mortality rate.

PMID- 10083991
TI  - The anesthetic record: accuracy and completeness.
AB  - PURPOSE: To evaluate if anesthesia training and experience influenced chart
      completion and accuracy. METHODS: One hundred and twenty-four subjects, including
      medical students, anesthesia residents and community and university based
      clinical anesthesiologists, were given a standardized patient in a simulator
      environment and asked to conduct induction and maintenance of anaesthesia. Three
      critical events were introduced resulting in changes in BP, HR, PETCO2 and SpO2.
      Subjects were instructed to manage the patient and the anesthetic chart, as was
      their customary practice. Discrepancy, calculated as the difference between the
      actual and charted values divided by the actual physiological value was compared
      by level of training with a two-way repeated measures analysis of variance
      (ANOVA) for all four physiological variables. The completeness of charting,
      defined as at least one data point recorded for each of the four physiological
      variables of the three critical events, was compared across level of training,
      age of participants and number of years in practice. RESULTS: The overall
      completeness of charting remained low (< 37%) with no relationship based on the
      anesthesiologist's age, level of training or number of years in practice. There
      was discrepancy in charting for all physiological variables (HR, BP, PETCO2 and
      SpO2, P < 0.0001), with a marked difference in the degree of discrepancy within
      each level of training. Training resulted in no differences in charting
      discrepancy. CONCLUSION: Charting of data to the anesthetic record remained
      incomplete and inaccurate in all groups based on level of training, age and
      number of years in practice.

PMID- 10083992
TI  - Is skin puncture beneficial prior to arterial catheter insertion?
AB  - PURPOSE: To compare the insertion time and incidence of catheter damage between
      skin puncture (SP) and no skin puncture (NP) techniques prior to arterial
      catheter insertion in patients undergoing neurosurgery. METHODS: Patients
      undergoing surgery for intracranial tumours or cervical spine lesions were
      randomized to receive either SP or NP prior to arterial catheter insertion. The
      total insertion time, number of passes made, number of catheters used, method of
      insertion (direct or transfixation) and whether catheter was inserted with
      patients awake or anesthetised were recorded. After removal, catheters were
      examined microscopically for damage. RESULTS: Eighty-two patients, 36 in SP group
      and 46 in NP group were recruited. Microscopic damage was seen in 36.5% of
      catheters and there was no difference between the two groups. The mean/median
      insertion time were 180/62 sec and 205/77 sec for SP and NP respectively (P:NS).
      The insertion time was shorter for the direct than for the transfixation
      technique with median of 42 vs 174 sec (P = 0.001). CONCLUSION: There are no
      differences in insertion time or catheter damage between skin puncture and no
      skin puncture techniques prior to arterial catheter insertion. The practice of
      skin puncture may be abandoned resulting in decreased risk of needlestick injury.

PMID- 10083993
TI  - Volume kinetics of Ringer solution after surgery for hip fracture.
AB  - PURPOSE: To study the time course of volume changes during and after infusion of
      Ringer's solution in elderly patients after a standardised trauma. METHODS: The
      kinetics of 12.5 ml.kg-1 Ringer's solution infused over 30 min were studied in
      ten patients one day after surgery for hip fracture (mean age, 70 yr) and in an
      age- and sex-matched control group. Hemodilution, as measured every five minutes
      for 90 min, was used to calculate the size of the fluid space expanded by the
      fluid (V) and the elimination rate constant (kr). The baseline fluid balance
      status in the patients and the controls was compared by bioelectrical impedance
      analysis. RESULTS: The size of V was 4.1 +/- 0.51 (mean +/- SEM) in the patients
      and 3.4 +/- 0.21 in the controls (P:NS) while the corresponding results for kr
      were 85 +/- 12 and 166 +/- 27 ml.min-1, respectively (P < 0.04). Bioelectrical
      impedance analysis showed that the extracellular fluid space and the total body
      water volumes did not differ between the two groups. Computer simulations based
      on the data obtained for V and kr indicate that trauma increases the dilution of
      the plasma volume and the retention of fluid in response to slow and moderate
      infusion rates, while these indices of short-term changes in fluid balance remain
      the same in the two groups during very rapid infusion of Ringer's solution.
      CONCLUSION: A slower elimination rate increased dilution of plasma and retention
      of fluid when Ringer's solution was infused in elderly trauma patients.

PMID- 10083994
TI  - Systemic thermal injury in anesthetized rabbits causes early pulmonary vascular
      injury that is not ablated by lazaroids.
AB  - PURPOSE: To study the effects of a systemic thermal injury on the pulmonary
      vasculature with and without inhibitors of lipid peroxidation (U74389G). METHODS:
      In a prospective, placebo control, randomized, and blinded multi-group study,
      burn shock was induced by scalding thermal injury (65C) to 35% body surface area
      in rabbits (n = 28). Hemodynamics and gas exchange were followed for 240 min post
      burn in four groups: No Burn, Burn-Control, Burn-U74 (10 mg.Kg-1 U74389G), No
      Burn-U74 (10 mg.Kg-1 U74389G). RESULTS: Scald resulted in early pulmonary injury
      as measured by increased pulmonary vascular resistance in the pooled Burn group
      compared with the No Burn groups (942 +/- 358 vs 605 +/- 255 dynes.sec-1.cm-5
      respectively, P < 0.05). These pulmonary changes were associated with alveolar
      sequestration of leukocytes (4.8 +/- 2.9 vs 17.7 +/- 6.0 cells x 10(9).L-1, P <
      0.05) in the No Burn and Burn groups respectively. Histological evidence of
      decreased neutrophil sequestration after scald injury was present in U74 treated
      animals (3+ vs 2+, P < 0.05 in the Burn and No Burn groups respectively and 2+ vs
      2+, P > 0.05 in the Burn-U74 and No Burn-U74 groups respectively) although
      bronchial alveolar lavage still demonstrated neutrophil sequestration (5.3 +/-
      2.5 vs 12.2 +/- 3.3 cell 10(9).L-1, P < 0.05 in No Burn-U74 and Burn-U74 groups
      respectively). Similarly, circulating white blood cells were increased in the
      Burn group but not Burn-U74 group four hours post burn. The increase in pulmonary
      vascular resistance after burn was not altered by administration of U74.
      CONCLUSIONS: Systemic burn results in early pulmonary vascular changes associated
      with leukocyte sequestration. After scald injury administration of lazaroids
      (U744389G) did not lessen pulmonary vascular resistance changes but did reduce
      neutrophil sequestration.

PMID- 10083995
TI  - Propofol does not affect the canine cardiac conduction system under autonomic
      blockade.
AB  - PURPOSE: To determine the effects of propofol on the cardiac conduction system in
      dogs with pharmacological autonomic blockade. METHODS: In eight mongrel dogs
      receiving 6 mg.kg-1.hr-1 propofol and vecuronium under pharmacological autonomic
      blockade with atropine and propranolol the infusion rates of propofol were
      increased from 6, (baseline), to 12, 18 and 24 mg.kg-1.hr-1 at 60-min intervals.
      An electrophysiological study assessed sinus rate, sinus node recovery time,
      corrected sinus node recovery time, intraatrial conduction time, AV nodal
      effective refractory period, Wenckebach cycle length and AV conduction times.
      Electrocardiographical variables and arterial pressures were also measured. All
      measurements were repeated at 30 min after the beginning of each infusion of
      propofol. RESULTS: Propofol did not produce direct effects on the
      electrophysiological or electrocardiographical variables at any infusion rates.
      Heart rates did not change at higher infusion rates in the presence of decreases
      in arterial pressures. CONCLUSION: Propofol did not affect the cardiac conduction
      system in the presence of autonomic blockade. Thus, the direct cardiac effects of
      propofol do not play a causative role in the genesis of propofol-associated
      bradyarrhythmias.

PMID- 10083996
TI  - Neuroleptanesthesia: current status.
AB  - PURPOSE: To review the current status and possible future of
      neuroleptanalgesia/anesthesia, techniques that may be nearly extinct. SOURCE:
      Articles from 1966 to present were obtained from the Current Science and Medline
      databases. Search terms include neurolepananalgesia/anesthesia, conscious
      sedation, droperidol, benzodiazepines, propofol, ketamine, and opioids.
      Information and abstracts obtained from meetings on this topic helped complete
      the collection of information. PRINCIPAL FINDINGS: Droperidol/fentanyl may still
      be clinically indicated in the management of surgical seizure therapy for
      electrocorticography. However, the high incidence of post-operative sedation and
      restlessness discourage its use for other surgical or diagnostic procedures. Many
      surgical interventions, once thought ideally suited for neuroleptic agents, now
      meet better success with newer medications. The use of midazolam and/or propofol,
      in association with newer opioids, provides ideal anesthetic combinations.
      CONCLUSION: The advantages of newer anesthetic agents have redefined the clinical
      indications for neuroleptanesthesia. In routine modern anesthesia, anxiolysis,
      sedation, and/or analgesia is better provided, with quicker recovery, by the new
      pharmacokinetic and pharmacodynamic characteristics of recent medications than by
      the neuroleptic component of neuroleptanesthesia.

PMID- 10083997
TI  - Detection of retroperitoneal hemorrhage by transesophageal echocardiography
      during cardiac surgery.
AB  - PURPOSE: To present a case of massive retroperitoneal hemorrhage during
      cardiopulmonary bypass (CPB) which was detected using transesophageal
      echocardiography (TEE). CLINICAL FEATURE: A 50-yr-old man suffering from severe
      mitral regurgitation (MR) was admitted for mitral valvuloplasty. After the
      beginning of CPB, the volume in the reservoir was noticed to be gradually
      decreasing. Although venous cannulation had been properly performed, TEE showed
      an echo free space around the liver, the spleen and in front of the abdominal
      aorta showed intraabdominal hemorrhage. After cardiac surgery, emergency
      laparotomy revealed about 5,000 ml of blood in the retroperitoneal space probably
      as a result of femoral artery cannulation prior to CPB. Hemostasis was achieved,
      and the patient made complete cardiac and neurological recovery. Retrospective
      review of the TEE imaging revealed that the kidneys were surrounded by blood
      bilaterally confirming the diagnosis of retroperitoneal hemorrhage. CONCLUSION:
      Retroperitoneal hemorrhage during CPB is rare, but may be lethal. Transesophageal
      echocardiography is a useful monitor not only to evaluate cardiac performance,
      but also to detect unexpected intraabdominal bleeding during cardiac surgery.

PMID- 10083998
TI  - An uncommon mechanism of brachial plexus injury. A case report.
AB  - PURPOSE: To report a case of brachial plexus injury occurring on the
      contralateral side in a patient undergoing surgery for acoustic neuroma through
      translabrynthine approach. CLINICAL FEATURES: A 51-yr-old woman underwent surgery
      for acoustic neuroma through translabrynthine approach in the left retroauricular
      area. She had a short neck with a BMI of 32. Under anesthesia, she was placed in
      supine position with Sugita pins for head fixation. The head was turned 45
      degrees to the right side and the neck was slightly flexed for access to the left
      retroauricular area, with both arms tucked by the side of the body.
      Postoperatively, she developed weakness in the right upper extremity comparable
      with palsy of the upper trunk of the brachial plexus. Hematoma at the right
      internal jugular vein cannulation site was ruled out by CAT scan and MRI. The
      only remarkable finding was considerable swelling of the right
      sternocleidomastoid and scalene muscle group, with some retropharyngeal edema. An
      EMG confirmed neuropraxia of the upper trunk of brachial plexus. She made a
      complete recovery of sensory and motor power in the affected limb over the next
      three months with conservative treatment and physiotherapy. CONCLUSIONS: Brachial
      plexus injury is still seen during anesthesia despite the awareness about its
      etiology. Malpositioning of the neck during prolonged surgery could lead to
      compression of scalene muscles and venous drainage impedance. The resultant
      swelling in the structures surrounding the brachial plexus may result in a severe
      compression.

PMID- 10083999
TI  - Complete upper airway obstruction during awake fibreoptic intubation in patients
      with unstable cervical spine fractures.
AB  - PURPOSE: To describe the presentation and management of complete upper airway
      obstruction with life threatening arterial oxygen desaturation that occurred
      during attempted awake fibreoptic intubation in two patients presenting with
      unstable C-spine injury. CLINICAL FEATURE: Complete upper airway obstruction
      occurred during awake fibreoptic intubation of two men (ASA II; 68 & 55 yr old)
      presenting with unstable C-spine fractures. In both cases, bag and mask
      ventilation with CPAP failed to relieve the progressive hypoxemia. A surgical
      airway was established urgently to oxygenate the two patients who were suffering
      progressive life-threatening oxygen desaturation. One patient had trans
      cricothyroid jet ventilation performed through a 16G intravenous cannula prior to
      an urgent tracheostomy. In the other patient, an emergency tracheostomy was
      inserted. Interestingly, both patients had been sedated in the Neurosurgical
      Intensive Care Unit with morphine and benzodiazepines before their scheduled
      surgeries. The most likely etiology for the complete upper airway obstruction was
      laryngospasm due to inadequate topicalization of the airway and additional
      sedation given in the operating room. Neither patients suffered any new
      neurological deficits following these events. They went on to have uneventful
      surgeries. CONCLUSION: This case report suggest that prior to awake fibreoptic
      intubation, oxygenation, adequate topicalization with testing to verify the lack
      of pharyngeal and laryngeal responses and careful assessment of sedation levels
      in the operating room are prudent for a safe endoscopic intubation.

PMID- 10084000
TI  - Efficacy and safety of the laryngeal mask airway vs Guedel airway following
      tracheal extubation.
AB  - PURPOSE: To compare the safety and efficacy of the laryngeal mask airway (LMA)
      with the Guedel airway during the recovery period. METHODS: In a prospective
      randomised trial in the Post Anesthesia Care Unit (PACU), 52 patients (ASA 1 and
      2) were randomised to receive either a laryngeal mask airway (LMA: n = 26) or a
      Guedel airway (n = 26) during the recovery period after middle ear surgery. Ease
      of airway maintenance was graded and the presence of coughing was noted.
      Peripheral arterial oxygen saturation (SpO2) was measured continuously by pulse
      oximetry in the PACU. Readings were taken on arrival (time 0) and for five
      minutes afterwards. RESULTS: There was no difference in sex, age, weight or
      incidence of smoking between the two groups. In the LMA group 25 patients
      required no airway manipulation and only one patient required repositioning of
      the LMA. In the Guedel group severe difficulty maintaining the airway was
      experienced in two patients, moderate difficulty in five patients and mild
      difficulty in 12 patients. Seven patients required no airway manipulation. The
      LMA group showed higher ease of airway maintenance scores, (P = < 0.0001) and
      less coughing (P = 0.0496). At time 0 and at one minute the LMA group had higher
      median SpO2 (97% and 97%) than the Guedel group (95% and 96%), (P = 0.0002 and
      0.0362). There was no further difference in SpO2. CONCLUSIONS: The LMA provides
      easier airway maintenance, less coughing and initially higher median SpO2 when
      compared with the Guedel airway in the recovery period.

PMID- 10084001
TI  - Awake tracheal intubation through the intubating laryngeal mask.
AB  - PURPOSE: To report successful awake insertion of the intubating laryngeal mask
      (Fastrach) and subsequent tracheal intubation through it, in a patient with
      predicted difficult tracheal intubation, due to limited mouth opening, and
      difficult ventilation through a facemask, due to a large mass at the corner of
      the mouth. CLINICAL FEATURES: A 53-yr-old woman with a large post-gangrenous mass
      on the right cheek to the angle of the mouth was scheduled for its resection. The
      right side of her face was damaged by a bomb attack followed by cancrum oris 50
      yr ago. The distance between the incisors during maximum mouth opening was 2 cm
      and that between the gums on the right side < 1 cm. After preoxygenation and 50
      micrograms fentanyl and 30 mg propofol i.v., propofol was infused at 2 mg.kg-1.hr
      1. Lidocaine, 8%, was sprayed on the oropharynx. A #4 intubating laryngeal mask
      was inserted with a little difficulty. A fibrescope was passed through a 7.5-mm
      ID RAE tracheal tube, and the combination was easily passed through the laryngeal
      mask into the trachea. General ansthesia was then induced. Finally, the
      intubating laryngeal mask was removed, while the RAE tube was being stabilized
      using an uncuffed 6.0-mm ID tracheal tube. CONCLUSION: Awake tracheal intubation
      through the intubating laryngeal mask is a useful technique in patients with
      limited mouth opening in whom ventilation via a facemask is expected to be
      difficult.

PMID- 10084002
TI  - Acute respiratory alkalosis associated with low minute ventilation in a patient
      with severe hypothyroidism.
AB  - PURPOSE: Patients with severe hypothyroidism present unique challenges to
      anesthesiologists and demonstrate much increased perioperative risks. Overall,
      they display increased sensitivity to anesthetics, higher incidence of
      perioperative cardiovascular morbidity, increased risks for postoperative
      ventilatory failure and other physiological derangements. The previously
      described physiological basis for the increased incidence of postoperative
      ventilatory failure in hypothyroid patients includes decreased central and
      peripheral ventilatory responses to hypercarbia and hypoxia, muscle weakness,
      depressed central respiratory drive, and resultant alveolar hypoventilation.
      These ventilatory failures are associated most frequently with severe hypoxia and
      carbon dioxide (CO2) retention. The purpose of this clinical report is to discuss
      an interesting and unique anesthetic presentation of a patient with severe
      hypothyroidism. CLINICAL FEATURES: We describe an unique presentation of
      ventilatory failure in a 58 yr old man with severe hypothyroidism. He had
      exceedingly low perioperative respiratory rate (3-4 bpm) and minute ventilation
      volume, and at the same time developed primary acute respiratory alkalosis and
      associated hypocarbia (P(ET)CO2 approximately 320-22 mmHg). CONCLUSION: Our
      patient's ventilatory failure was based on unacceptably low minute ventilation
      and respiratory rate that was unable to sustain adequate oxygenation. His
      profoundly lowered basal metabolic rate and decreased CO2 production, resulting
      probably from severe hypothyroidism, may have resulted in development of acute
      respiratory alkalosis in spite of concurrently diminished minute ventilation.

PMID- 10084003
TI  - Airway management: contents of a difficult intubation cart.

PMID- 10084004
TI  - Estimation of desflurane concentration using isoflurane channel in optical
      infrared analyzer.
AB  - PURPOSE: To estimate desflurane concentration on the isoflurane channel in an
      optical infrared analyzer using a simple regression equation. METHODS: Desflurane
      in concentrations of 0% to 3% in 0.5% increments and 3% to 12% in 1% increments
      in 2 L.min-1 oxygen was delivered simultaneously to an Ohmeda 5250 RGM desflurane
      channel, an Ohmeda 5250 RGM isoflurane channel, and a Datex Capnomac Ultima
      isoflurane channel at room temperature and atmospheric pressure. For each
      concentration increment, the displayed gas concentrations were recorded. By
      comparing the readings from the desflurane channel of Ohmeda RGM and the
      isoflurane channels from Ohmeda RGM and Datex Capnomac Ultima respectively, the
      linear regression relationship and the slope of the fitted line (conversion
      factor) between two channels were obtained. Similar measurements were performed
      using 2 L.min-1 mixture of nitrous oxide 50% and oxygen 50%. The measurements
      were repeated with different monitors three months later. RESULTS: All four
      analysers tested were linear (r2 > 0.9) for measuring desflurane using isoflurane
      channels over the range of concentrations studied on two different days. The
      accuracy of the estimation using the mean conversion factor of the four monitors
      was within 10% error from the readings of the commercially available desflurane
      channel analyzer. There was no noticeable effect on the slope (conversion factor)
      of the linear regression with O2 100% or 50/50 mixture of N2O and O2. CONCLUSION:
      The concentration of desflurane can be estimated by a simple conversion factor
      using an isoflurane channel of an infrared system.

PMID- 10084005
TI  - The difficult airway.

PMID- 10084006
TI  - Respiratory arrest following intrathecal sufentanil.

PMID- 10084007
TI  - Respiratory arrest following intrathecal sufentanil.

PMID- 10084008
TI  - Sevoflurane vaporizers.

PMID- 10084009
TI  - Another use of the "Bair Hugger".

PMID- 10084010
TI  - Increased airway pressure caused by a ventilator.

PMID- 10084011
TI  - Manual pump failure.

PMID- 10084012
TI  - Birth weight of neonates as an indicator of morbidity and mortality in adult age
      and factors which influence it.
AB  - In 28 neonates born by spontaneous delivery to healthy mothers with a normal
      course of gestation venous umbilical blood was examined to assess the
      immunoreactive insulin concentration. Moreover, the birth weight of the neonates
      was recorded, the weight increment of the mother during pregnancy and the body
      mass index at the end of gestation. By means of a questionnaire and the computer
      programme Progana the dietary intake of the mothers at the end of pregnancy was
      assessed and compared with recommended allowances. The assembled data were
      evaluated statistically by assessment of the correlation coefficient. The
      investigation revealed that the birth weight of the neonates in the group does
      not correlate with the immunoreactive insulin concentration in umbilical venous
      blood. Although the dietary intake of the mothers at the end of pregnancy is not
      ideal (fat and cholesterol intake predominates over carbohydrate and protein
      intake), it does not correlate with the birth weight of the neonates nor with the
      immunoreactive insulin concentration in umbilical venous blood. From these
      results the conclusion is drawn that neonates with a low birth weight do not have
      a higher plasma insulin concentration after delivery and that the mother's diet
      at the end of pregnancy does not influence the birth weight and insulin level in
      neonates.

PMID- 10084013
TI  - Visceral and cutaneous leishmaniasis (report of 2 cases).
AB  - Leishmaniasis is an endemic, sporadic infection in many parts of the world.
      Turkey is geographically unique in linking Asia and Europe. Of special interest
      is leishmaniasis, as various forms of this disease have long been reported in the
      surrounding regions. Visceral and cutaneous leishmaniasis are endemic in the
      western and southeastern parts of Turkey, respectively. Here, we report a
      cutaneous and a visceral leishmaniasis case, to draw attention to the increase in
      the incidence of leishmaniasis in Turkey. In the patient with cutaneous
      leishmaniasis, the ulcerative lesion on the cheek had persisted for two months
      before admittance to the hospital. Direct smears prepared from this lesion were
      negative for leishmania amastigotes whereas the promastigote forms were
      maintained in NNN (Novy-MacNeal-Nicolle) medium. The second patient was
      hospitalized with a prediagnosis of haematological malignancy, but the smears
      prepared from the bone marrow aspirates revealed leishmania amastigotes and
      promastigotes were seen on the smears from NNN cultures. These two reports mark
      the importance of inoculation of the specimens to NNN medium for the recovery of
      the promastigote forms. Cutaneous and visceral leishmaniasis have become endemic
      in considerable number of foci in Turkey, possibly due to the cessation of vector
      control programmes and increase in the agricultural and irrigation areas. These
      two reports also point out the increased prevalence of leishmaniasis in Turkey
      after 1980's.

PMID- 10084014
TI  - Immunological disorders in men exposed to metallic mercury vapour. A review.
AB  - The awareness of the effects of metallic mercury vapour on the human immune
      system has increased only in the last decade. The regulatory guidelines relating
      to testing for immunotoxicity of metals are not standardized so far. A full
      understanding of the relevance of the tests to man is still incomplete.
      Immunotoxicity investigation of metals in rodents, with subsequent extrapolation
      to man, forms the basis of human risk assessment. Human contact with mercury
      vapour is mainly in chloralkali plants and in factories producing controlling and
      measuring devices. When the immune system acts as a target of xenobiotic insults,
      the result can be a decreased resistance to infection, cancers, or immune
      disregulation that can induce the development of allergy, or autoimmunity (Fig.
      1). This article reviews literature data and our studies concerning the
      immunotoxicity of metallic mercury vapour. A number of data shows that mercury
      exerts a suppressing effect but another data suggest stimulating effects on the
      human immune system. The results of immunological monitoring of individuals
      exposed to mercury vapour were either positive or negative as well as borderline
      and uncertain as to the influence of mercury vapour on human immune system. The
      positive data had no influence on the resistance of workers to infections and
      neoplasms. Skin and mucosa hypersensitivity to metallic mercury is rare. No
      positive report that mercury vapour could be carcinogenic in man has appeared up
      to now.

PMID- 10084015
TI  - Electro-ionic microclimate and materials used in the indoor environment.
AB  - In 170 experiments relationships between 31 different materials used in indoor
      premises and ionization of the air in their proximity were assessed. The
      influence of temperature and relative humidity on ionization of air was studied.
      It was observed that the materials tested could be divided into four groups
      according to their behaviour towards ambient light negative ions. From the
      results obtained it follows that the more humid and thus more conductive the
      material in question, the greater is its influence on the ionization of the air.
      The most important criterion influencing the relationship of the material and
      ambient air ionization is the magnitude of the contacting surface of the material
      that is given by its ruggedness and structure. In natural materials considerable
      porosity may be expected. In contrast smooth surfaces without pores can be
      expected in materials produced by melting. Other physico-chemical properties of
      the materials are manifested in a more discrete way.

PMID- 10084016
TI  - Diet, smoking, and blood lipids in patients with combined familial
      hyperlipidaemia.
AB  - This study analysed the diet (based on a 7-day-record), smoking habits and basic
      anthropometric parameters of patients with familial combined hyperlipidaemia (N =
      154, 52% men, 48% women, mean age 55.73 +/- 12.95). These data were correlated
      with blood lipids and lipoproteins. In high-risk patients' diets we found not
      quantitative, but mostly qualitative shortcomings: the average energy intake was
      104% of the recommended daily intake (RDI), but 34% of the energy was derived
      from fats. The daily fat intake represented 137% of RDI, and 60 g were of animal
      and 24 g of vegetable origine. The protein intake was 120% of RDI (155% animal,
      75% vegetable protein), the carbohydrate intake was only 86% and the fibre intake
      71% of RDI. A very high intake both of cholesterol--139% of RDI and NaCl 151% of
      RDI--was recorded, while the intake of antioxidant vitamins C and E was only 82%
      and 35% of RDI, respectively. Current smoking was recorded in 51% of patients.
      Smokers had also a poorer diet: higher animal fat and protein, as well as a
      higher cholesterol intake, lower vegetable fat, protein, fibre and vitamin E
      intake. Surprisingly smokers were found to ingest more vitamin C than non
      smokers. As to blood lipids: smokers vs. non-smokers had the following values in
      mmol/l (SD): total cholesterol 7.8 (+/- 1.3) vs. 7.7 (+/- 1.82), triacylglycerols
      3.27 (+/- 2.13) vs. 3.2 (+/- 3.11), HDL-cholesterol 1.25 (+/- 0.39) vs. 1.36 (+/-
      0.43), LDL-cholesterol 5.11 (+/- 1.39) vs. 4.95 (+/- 1.51), and, in g/l,
      apolipoprotein A1 1.8 (+/- 0.30) vs. 1.66 (+/- 0.35), apolipoprotein B 1.66 (+/-
      0.35) vs. 1.52 (+/- 0.44), lipoprotein (a) 0.36 (+/- 0.27) vs. 0.43 (+/- 0.50),
      all without statistical significance. For smokers vs. non-smokers anthropometric
      data were as follows (mean, SD): body mass index (BMI) 27.74 (+/- 3.77) vs. 27.02
      (+/- 3.30), waist/hip ratio (WHR) 0.895 (+/- 0.086) vs. 0.911 (+/- 0.093), and %
      of body fat 29.6 (+/- 7.4) vs. 27.9 (+/- 7.9). Our conclusions suggest, that
      lifestyle choice are of great importance for patients with this serious genetic
      lipid metabolism disorder and that it is important to recognise the danger of
      risk factor cumulation in connection with cardiovascular diseases.

PMID- 10084017
TI  - Elimination of Yersinia enterocolitica by chlorine on fresh tomatoes.
AB  - The effect of temperature throughout 18 day-storage and the efficacy of different
      free chlorine concentrations in washing solutions upon the survival of Yersinia
      enterocolitica on surface of inoculated fresh tomatoes were studied. Two
      virulence plasmid-bearing strains. A. Y. enterocolitica W1024 0:9--a reference
      strain--and B. Y. enterocolitica B1 0:5 Lis Xz--a strain isolated from food in
      San Luis, Argentina, were assayed. Counts of both strains at 6 degrees C did not
      present significant changes during the first 4 days, but increased until day 15.
      Both strains were able to grow on tomatoes stored at 22 degrees C and 35 degrees
      C. At 22 degrees C maximum values were obtained on days 3 and 4, with a
      subsequent significant decrease. Highest counts were obtained at 37 degrees C. No
      detectable levels of viable cells were observed by using 500 ppm free chlorine
      washing solution. Non-inoculated tomatoes were analyzed for Y. enterocolitica
      with negative results. Zero tolerance for pathogenic Y. enterocolitica strains
      has been recommended for ready-to-use vegetables. Therefore, sanitary measures
      should be taken in the manipulation and storage of fresh tomatoes.

PMID- 10084018
TI  - Possibilities of long-term protection against blood-sucking insects and ticks.
AB  - Insecticidal and repellent properties and residual action of permethrin and
      deltamethrin and two commercial preparations Peripel 55 and Permanone were
      investigated under laboratory and field conditions. The tests were conducted on
      ticks, mosquitoes and houseflies. Permethrin in concentrations of 0.036-2.276
      mg.m-2 caused 90-100% mortality and deltamethrin in concentrations of 0.012-0.75
      mg.m-2 induced 78-100% mortality in ticks after 24 hrs exposure (Table 1). Good
      repellent properties of the preparation Peripel 55 were confirmed in experiments
      on mosquitoes Aedes aegypti (Table 2 and Fig. 1). Experiments confirmed good
      residual effects (Fig. 3 and 4) of the preparations tested. Peripel 55 retained
      100% effectiveness up to 4 months and following two washings. The preparation
      Permanone exhibited 100% effectiveness for 1 month and a decrease in
      effectiveness to 52% after the first washing. In the period from June to
      September, the repellent properties of Permanone were observed in a group of 17
      forestry women workers in a field trial. The index of repellency ranged from 57
      to 80 (average 71) in June and July and from 40 to 100 (average 74) in August and
      September. The difference in the number of ticks that clung to the workers in the
      experimental group who had their clothes treated with the preparation tested was
      significant in comparison with the control group at p < 0.1, 0.05 and 0.01.

PMID- 10084019
TI  - Epidemiology of smoking habit in adolescents. Suggestions for prevention.
AB  - The results of a cross-sectional questionnaire study on smoking in 1,571 pupils
      of secondary schools in Martin, Slovakia (average age 15.7 y. +/- 1.0) are
      presented. Prevalence of regular smoking (min. 1 cigarette/day) was in 24.8% of
      boys and in 14.3% of girls. Higher prevalence was in pupils of apprentice
      schools. Association between smoking or respondents and their parents were
      stronger in case of mothers and their children, namely girls. Higher educational
      level of parents was followed by a decrease of smoking in girls. Girls appear to
      be more influenced by family background than boys. The authors emphasise the
      importance of primary prevention of smoking in pupils, namely within the school
      based programmes, since smoking habit in these age groups is still developing.
      The study design can be used as a model for further studies of that kind.

PMID- 10084020
TI  - Tick-borne encephalitis and Lyme borreliosis: comparison of habitat risk
      assessments using satellite data (an experience from the Central Bohemian region
      of the Czech Republic).
AB  - The vegetation types have been used as the indicators of an ecosystem suitable
      for high incidence of Ixodes ricinus ticks and their hosts, for the circulation
      of tick-borne diseases pathogens and, accordingly, for the existence of natural
      foci of these infections, namely tick-borne encephalitis (TBE) and Lyme
      borreliosis (LB). The method of remote sensing offers a suitable solution to this
      problem. We attempted to prepare the habitat risk assessment maps on the
      territory (11,500 km2) of Central Bohemia (Czech Republic) using Landsat 5 TM
      imagery. Nine forest classes have been recognized in the satellite data and
      further identified in a field checking botanical survey. Beside the conclusions
      dealing with the importance of different plant types for I. ricinus occurrence,
      also the epidemiological TBE and LB maps based on human cases contracted in the
      territory under study were exploited for the evaluation of particular forest
      classes significance, and for the comparison of results achieved. Apart from a
      general pattern of risk gradation from coniferous to deciduous wood types, both
      TBE and LB data suggest a specific position of the heterogeneous deciduous wood
      class (including mainly young deciduous stands and stand ecotones with highly
      heterogeneous structure). Epidemiological significance of the other particular
      forest classes was assessed by the degrees of positive class-to-risk associations
      (see Table 1 and 2).

PMID- 10084021
TI  - Relation between concentration of lead, zinc and lysozyme in placentas of women
      with intrauterine foetal growth retardation.
AB  - Intrauterine foetal growth retardation (IUGR) implies increased risk of morbidity
      and mortality of the newborn. Aetiology of intrauterine retardation is probably
      multifactorial and may include maternal infection, malnutrition, placental
      dysfunction, hypertension, toxaemia, smoking, professional and environmental
      exposure. The work concentrates on the lead, zinc and lysozyme levels in blood
      and placental tissues of 50 females in the IUGR group and 43 females from a
      control group. Statistically significant differences in zinc and lead levels
      between the compared group were found. The IUGR group had lower zinc and higher
      lead levels. A significant negative correlation of zinc and lead levels was
      observed. We found a statistically significant relationship between lead levels
      in placental tissues and the age of the pregnant women. Higher age is associated
      with higher lead levels in placental tissue, whereas zinc levels decrease. In
      placental tissues of pregnant females of the IUGR group higher lysozyme levels
      were found. On the basis of the discussed results the authors recommend zinc
      supplementation during the pregnancy.

PMID- 10084022
TI  - Encephalitozoon intestinale infection in an AIDS patient--a case report.
AB  - The first case of one of the most frequent intestinal microsporidians,
      Encephalitozoon intestinale, is reported from an AIDS patient in the Czech
      Republic. The patient experienced diarrhoea and was found to have microsporidia
      spores in stool. Species determination by electron microscopy confirmed the
      diagnosis of the microsporidian, E. intestinale. The CD4-count at the time of the
      diagnosis was 73 cells/mm3, IRI = 0.21. Only after symptomatic therapy and
      rehydration the patient stopped the complaining, and although he refused an
      antimicrosporidial therapy, the CD4-count one month later increased to 200
      cells/mm3 and patient didn't suffered from diarrhoea. Six months after the first
      finding of microsporidia, the patient was admitted to the hospital care for
      progressive encephalopathy and developing wasting syndrome again with the
      intermittent diarrhoea. The patient was treated with albendazole at that time.
      Nevertheless, after 14 days of albendazole therapy, he still remained positive
      for E. intestinale spores in the stool (urine specimens remained negative for all
      the time). The patient died after a two-month hospitalisation and the apparent
      cause of death was purulent bronchopneumonia, wasting syndrome with
      microsporidiosis, and HIV encephalopathy. Generalised mycobacteriosis (MAC) was
      also found from the autopsy material.

PMID- 10084023
TI  - Plesiomonas shigelloides and its serovars in animals in the Czech Republic-
      region Moravia.
AB  - In the period of 1994-1997, 4,552 samples of sectional, clinical material and
      environment were examined for the presence of Plesiomonas shigelloides. In 55
      cases (1,21%) Plesiomonas shigelloides was isolated. Within 55 isolated strains,
      26 serovars have been successfully identified. Among other secured cases was
      Plesiomonas shigelloides isolated in pig (Sus scrofa domestica), mouse Mus
      musculus), binturong (Arctictis binturong) and raccoon (Pocyon lotor). In
      mandarin duck (Aix galericulata) the strain of Plesiomonas shigelloides with a
      new 0 antigen-097 was isolated. In regard of the particular biological classes,
      the isolation of Plesiomonas shigelloides in fish (2.63%) predominate, followed
      by reptiles (1.66%), mammals (0.94%) and birds (0.79%). Plesiomonas shigelloides
      in amphibians was not demonstrated. This work surveys the incidence of
      Plesiomonas shigelloides and its serovars in animals in the region Moravia in the
      Czech Republic.

PMID- 10084024
TI  - Health effects of indoor air pollutants--difficulties of evaluation.
AB  - The quality of indoor environment has become a matter of growing concern in many
      countries over the twenty years and even in our countries the interest in indoor
      air quality (IAQ) is still growing, but slowly. There is a lot of studies on
      different aspects of IAQ including some in CEEC, but there is still a lot of
      uncertainty in indoor air quality evaluation. Most of the common methods of risk
      assessment cannot be used from the different reasons. There are many results from
      different countries and different studies and according to research results,
      indoor climate in buildings varies a lot. So varies also human reactions. Only
      some symptoms are relatively clear in diagnostics (e.g. Building Related
      Illnesses) but mostly in practice we meet other than such problems. Therefore we
      should be very careful in evaluation of the health effect of indoor environment,
      especially in dose-response assessment.

PMID- 10084025
TI  - Is antiendothelial cell antibody the murder weapon in systemic sclerosis?

PMID- 10084026
TI  - The role of arthroscopy in early arthritis.

PMID- 10084027
TI  - The combination of methotrexate, sulfasalazine and hydroxychloroquine is highly
      effective in rheumatoid arthritis.

PMID- 10084028
TI  - Topical non-steroidal anti-inflammatory drugs are effective in acute and chronic
      pain conditions.

PMID- 10084029
TI  - Overdiagnosis and overtreatment of Lyme disease leads to inappropriate health
      service use.

PMID- 10084030
TI  - Systemic lupus erythematosus and tracheal stenosis.

PMID- 10084031
TI  - A trial of clodronate-liposomes as anti-macrophage treatment in a sheep model of
      arthritis.
AB  - OBJECTIVE: Our previous research has concerned the role of macrophages in joint
      inflammation in rheumatoid arthritis. We have therefore been interested in
      liposomes containing clodronate as an antimacrophage treatment for arthritis. We
      have used the antigen-induced arthritis model in sheep to evaluate the effect of
      clodronate liposomes. METHODS: Arthritis was induced in the right hock joint (day
      0). We were able to demonstrate uptake of liposomes into macrophages within the
      inflamed joint lining. On day 7, sheep were given a single intra-articular
      injection of clodronate liposomes (group 1, n = 10) or saline liposomes (group 2,
      n = 10). A further 6 sheep (group 3) had no arthritis and no treatment. RESULTS:
      No difference in joint diameter was observed between the sheep in group 1
      (clodronate) and group 2 (saline treated). Both groups had joint swelling which
      persisted until the end of the trial (day 20). Histologic scoring was also
      similar in group 1 and group 2 animals, and both were worse than group 3.
      CONCLUSION: In vitro studies have shown that interaction of liposomes with
      neutrophils and monocytes stimulates a respiratory burst. Despite this possible
      pro-inflammatory effect we did not observe any increase in joint diameter
      following liposome injection. Thus we were unable to demonstrate a therapeutic
      effect of a single dose of clodronate liposomes in this large animal model of
      antigen-induced arthritis.

PMID- 10084032
TI  - Non-invasive assessment of digital vascular reactivity in patients with primary
      Raynaud's phenonenon and systemic sclerosis.
AB  - OBJECTIVE: To examine digital microvascular responses in patients with primary
      Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and compare these to the
      responses in healthy control subjects. METHODS: Digital microvascular responses
      to repeated episodes of iontophoresis of acetylcholine chloride (endothelial
      dependent), sodium nitroprusside (endothelial-independant) and adrenaline were
      measured using dual-channel laser Doppler in 8 healthy control subjects, 8
      patients with PRP and 8 patients with SSc. RESULTS: There were no significant
      differences in responses between groups. For each chemical the greatest response
      was generally seen in period 7 of the protocol (after the third episode of
      iontophoresis). For acetylcholine chloride in period 7, the age and baseline
      adjusted ratio of the maximum response of PRP to control was 0.93, 95% CI (0.26,
      3.38) and for SSc to control it was 0.60, 95% CI (0.13, 2.81). For sodium
      nitroprusside in period 7, this age and baseline adjusted ratio of the maximum
      response of PRP to control was 1.31, 95% CI (0.74, 2.32) and for SSc to control
      it was 1.35, 95% CI (0.68, 2.67). For adrenaline in period 7, the age and
      baseline adjusted ratio of PRP to control was 1.51, 95% CI (0.79, 2.89) and for
      SSc to control it was 2.18, 95% CI (1.01, 4.69). CONCLUSION: This study
      demonstrates the usefulness of iontophoresis of vasoactive chemicals, combined
      with laser Doppler blood flowmetry, in the non-invasive assessment of dermal
      microvascular responses. One possible explanation for the lack of difference in
      responses between groups is that vasoactive chemicals other than those discussed
      are important in the pathophysiology of primary and secondary Raynaud's
      phenomenon.

PMID- 10084033
TI  - The accuracy of diagnosing neuropsychiatric systemic lupus erythematosus in a
      series of 49 hospitalized patients.
AB  - OBJECTIVE: Neuropsychiatric manifestations in patients with systemic lupus
      erythematosus (SLE) originate from immune-mediated disease (primary
      neuropsychiatric SLE) or from other pathogenetic mechanisms indirectly related to
      SLE (secondary neuropsychiatric SLE). The objective of this study is to describe
      the clinical practice of diagnosing NP-SLE and to assess how often the diagnosis
      of primary NP-SLE is changed to secondary NP-SLE and vice versa during the follow
      up period in a large series of hospitalized SLE patients. MATERIALS AND METHODS:
      Data was collected by means of retrospective evaluation of the charts of 191 SLE
      patients admitted during the period 1986 to 1995. RESULTS: Of 191 admitted SLE
      patients, 49 had developed neuropsychiatric signs and symptoms. At admission 30
      patients were classified as having primary NP-SLE and 19 patients secondary NP
      SLE. During follow-up the diagnosis was changed to primary NP-SLE in 2 patients
      initially diagnosed as suffering from secondary NP-SLE, and in two patients from
      primary to secondary NP-SLE. Seizures, cognitive deterioration, psychosis and
      organic brain syndrome were the most frequent manifestations in primary NP-SLE,
      whereas in secondary NP-SLE headache, seizures, paresis and organic brain
      syndrome prevailed. 47% of the primary NP-SLE patients were re-admitted to
      hospital because of recurrent neuropsychiatric manifestations within 4.5 years,
      while 10% died due to primary NP-SLE. The prognosis of secondary NP-SLE was
      dependent on the diagnosis. CONCLUSION: In the large majority of patients the
      initial diagnosis of primary or secondary NP-SLE made upon their admittance to
      hospital is confirmed during the long-term follow-up.

PMID- 10084034
TI  - Fluctuation of anti-Ro/SS-A antibody levels in patients with systemic lupus
      erythematosus and Sjogren's syndrome: a prospective study.
AB  - OBJECTIVE: To determine whether the titers of anti-Ro/SS-A (Ro) antibodies
      fluctuate during the course of SLE and Sjogren's syndrome (SS) in parallel with
      disease activity, and if such fluctuations could be used to predict disease
      flares. We also evaluated whether the anti-Ro profile (anti-Ro 52, anti-Ro 60)
      changes over time, since such information could provide new insights into the
      induction and regulation of anti-Ro autoimmunity. METHODS: Sixteen patients with
      SLE and 15 patients with SS, all anti-Ro/SS-A antibody positive, were followed up
      for two years at three-month intervals. Clinical and laboratory parameters of
      disease activity were examined. Determination of the anti-Ro/SS-A titer was
      performed by counterimmunoelectrophoresis and the fine anti-Ro antibody
      specificity was determined by immunoblotting. RESULTS: The titers of anti-Ro
      antibodies fluctuated during the course of the illness in both SLE and SS
      patients. In SLE patients these changes were not (except in one case) associated
      with disease activity nor were they predictive of disease flares. The same was
      true for the SS patients, with the exception of two patients with skin vasculitis
      in whom anti-Ro antibody titers fluctuated in parallel with the disease activity.
      The anti-Ro antibody (anti-Ro 60 kD, anti-Ro 52 kD) specificity did not change in
      any of the patients during the follow-up period. CONCLUSION: Anti-Ro antibodies
      could represent a valuable indicator of disease activity in SS patients with
      cutaneous disorders. They do not, on the other hand, reflect disease activity in
      patients with SLE. The stable antibody profile in both SLE and SS patients
      supports the hypothesis that autoantibody production is predominantly genetically
      regulated.

PMID- 10084035
TI  - The effects of recombinant human erythropoietin on autologous blood donation in
      rheumatoid arthritis patients with anaemia.
AB  - OBJECTIVES: The effect of recombinant human erythropoietin (rHuEPO) treatment on
      autologous blood donation was evaluated in anaemic patients with rheumatoid
      arthritis (RA) undergoing total joint replacement surgery. METHODS: A total of 56
      total knee or hip joint replacement operations were performed in the knee or hip
      joint in 36 anaemic RA patients (hemoglobin (Hb) concentration < 11.0 g/dl]. All
      of the patients received intravenous rHuEPO at a dose of 100-200 units/kg body
      weight three times a week for 3 weeks. An autologous blood donation of 800-1200 g
      was the goal for each patient. A refractory case was defined as a patient whose
      Hb level did not increase to 10.0 g/dl after 3 weeks of treatment with rHuEPO.
      The objective signs of arthritis were assessed by the Lansbury activity index
      (AI). During the treatment period, the patients underwent weekly hematological
      analyses, including routine hematology, serum iron, serum ferritin, C-reactive
      protein (CRP), and serum erythropoietin levels. RESULTS: The response to rHuEPO
      treatment was determined, and blood donation was possible in 47 of 56 joint
      replacements. In the other 9 operations, donation was not possible due to a poor
      response to rHuEPO. The mean Hb level before treatment in the refractory group
      (8.3 g/dl) was significantly lower than that in the responsive group (10.4 g/dl,
      p = 0.0002). During the treatment period, the mean erythropoietin level was above
      the normal limit in the refractory group. The mean AI for the refractory group
      tended to be lower than that in the responsive group. The mean pre-treatment CRP
      (6.4 mg/dl) and erythrocyte sedimentation rate (ESR) (87.1 mm/h) levels in the
      refractory group were significantly higher than those in the responsive group
      (CRP: 3.2 mg/dl, p = 0.008, ESR: 52.6 mm/h, p = 0.01). CONCLUSIONS: The control
      of disease activity prior to rHuEPO treatment is considered to a prerequisite for
      autologous blood donation. In addition, severe anaemia (Hb concentration < 8.0
      g/dl) appears to be another risk factor for refractoriness to rHuEPO treatment
      with the present protocol. A higher rHuEPO dose (> 200 units/kg/3 times a week
      for three weeks) was considered to be necessary in the refractory group.

PMID- 10084036
TI  - Serological and clinical markers of autoimmune disease in HCV-infected subjects
      with different disease conditions.
AB  - OBJECTIVE: To investigate whether the serological markers of autoimmunity and the
      clinical features of autoimmune disease which occur in hepatitis C virus (HCV)
      infected subjects are correlated to each other and/or to the clinical pattern of
      the disease. METHODS: Seventeen symptom-free, anti-HCV antibody positive
      subjects, 17 patients with chronic hepatitis C, 21 patients with mixed
      cryoglobulinemia (MC), and as controls 17 anti-HCV negative patients with
      dyspepsia were enrolled in a prospective study. A patient history, clinical
      examination, self-administered questionnaire and laboratory investigations
      (hepatic enzyme levels, serum HCV-RNA and anti-HCV antibody testing, and serum
      autoantibody profile) were performed to detect liver and/or autoimmune disease.
      RESULTS: Serological markers of autoimmunity and clinical findings of autoimmune
      disease were found to be more frequent in the HCV-infected patients considered as
      a whole than in controls. However, rheumatoid factor and clinical findings of
      autoimmune disease were more frequent in MC patients, while anti-smooth muscle
      antibodies not linked to symptoms or signs of autoimmune disease were detected in
      all groups of HCV-infected individuals, including healthy carriers and subjects
      who had recovered from a previous HCV infection. CONCLUSION: Anti-smooth muscle
      antibodies, a serological marker of autoimmunity, are detectable in HCV-infected
      subjects whatever their clinical status. Clinical findings of autoimmune disease
      prevalently occur in patients with mixed cryoglobulinemia.

PMID- 10084037
TI  - Tuberculosis prophylaxis in patients with steroid treatment and systemic
      rheumatic diseases. A case-control study.
AB  - OBJECTIVE: The aim of this study was to assess the impact of isoniazid
      prophylaxis in patients with systemic rheumatic diseases who attended a teaching
      hospital in Mexico City between 1987 and 1992. METHODS: In this case-control
      study, patients with systemic rheumatic diseases and tuberculosis (cases) were
      compared with patients with systemic rheumatic diseases without tuberculosis
      (controls). The groups were matched by year of hospital admission and rheumatic
      disease. Clinical charts were reviewed for: 1) isoniazid prophylaxis, defined as
      the administration of isoniazid 300 mg/day for 6 or more months in patients with
      exposure to steroids (prophylaxis with isoniazid was defined as complete,
      incomplete or any prophylaxis); 2) exposure to steroids: defined as the
      administration of prednisone > 15 mg/day (or its equivalent of another steroid)
      for 3 or more months before tuberculosis or recruitment into the study; 3)
      exposure to immunosuppressants, defined as the administration of any dose of
      azathioprine, methotrexate, cyclophosphamide, and/or 6-mercaptopurine, before
      tuberculosis in the cases or recruitment date in the controls; 4) reactivity to
      PPD; and 5) other relevant variables. RESULTS: Twenty cases and 66 controls were
      studied. A 70% decrease in the risk of developing tuberculosis was found among
      patients who received any prophylaxis with isoniazid as compared to controls: OR
      0.31, 95% CI 0.09-0.98, p = 0.03. A 97% decrease was seen in those patients who
      received complete prophylaxis: OR 0.034, 95% CI 0.0001-0.216, p < 0.0001. The
      protective effect of complete prophylaxis persisted even after controlling for
      other potential confounders, such as age, gender, rheumatic disease, duration of
      rheumatic symptoms, and exposure to steroids and/or immunosuppressants.
      CONCLUSION: The results of this study suggest that in countries with a high
      prevalence of tuberculosis the use of isoniazid (300 mg/day for 6 months) in
      rheumatic patients with exposure to prednisone (> 15 mg/day for three or more
      months) may be useful to prevent tuberculosis, independently of the results of
      the PPD reactivity test. However, a controlled clinical trial will be required to
      confirm these results.

PMID- 10084038
TI  - Periarticular corticosteroid treatment of the sacroiliac joint in patients with
      seronegative spondylarthropathy.
AB  - OBJECTIVE: To evaluate the efficacy of periarticular corticosteroid injection of
      the sacroiliac joint (SIJ) in patients with seronegative spondylarthropathy in a
      double blind, controlled study. METHODS: 20 patients with seronegative
      spondylarthropathy and clinical sacroiliitis entered the study. In 10 patients
      one affected SIJ was treated with periarticular injection of 1.5 ml (40 mg/ml)
      methylprednisoloneacetate and 1.5 ml (20 mg/ml) lignocaine (MP group), whereas 10
      patients received 1.5 ml isotonic sodium chloride and 1.5 ml (20 mg/ml)
      lignocaine (non-MP group). Clinical assessment at the onset of the study and
      after two months follow-up included the patients' estimation of pain in the SIJ
      by the visual analogue scale (VAS) and by a pain index which was calculated from
      tenderness and stressing tests on the SIJ. RESULTS: At the two months follow-up
      examination the VAS (p = 0.02) and the pain index (p = 0.01) had improved
      significantly in the MP group compared with the non-MP group. CONCLUSION: The
      results of our study indicate that the periarticular injection of
      methylprednisolone may be effective in the treatment of clinical sacroiliitis in
      patients with seronegative spondylarthropathy.

PMID- 10084039
TI  - Immunogenetics of mixed connective tissue disease in a Mexican Mestizo
      population.
AB  - OBJECTIVE: The aim of this study was to determine the HLA antigens in Mexican
      Mestizo patients with mixed connective tissue disease (MCTD). METHODS: We studied
      30 patients with MCTD and 99 healthy controls. HLA-A, -B, and -DQ antigens were
      typed by microlymphocytotoxicity assays. DRB1, DQA1 and DQB1 alleles were
      oligotyped. RESULTS: HLA-A2 and HLA-B35 were the most frequent MHC class I
      alleles in MCTD patients, although they were not statistically more frequent than
      in the controls. According to serological tests, the most frequent DQ allele in
      the patients was DQ1, which was statistically increased when compared with
      controls (p = 0.0051). By oligotyping, the DR1 allele and the DQB1*0501
      specificities were significantly increased in the patients vs. controls (p =
      0.032 and 0.027, respectively). CONCLUSION: The elevated levels of DQ1 found in
      Mexican MCTD patients, although weak, may indicate a particular genetic
      susceptibility, since there are previous reports of associations of other alleles
      (such as DR4) with MCTD in other populations. The increase in DQB1*0501 may
      account for the increase in DQ1. DQB1*0501 has also been reported in black
      patients with anti-RNP autoantibodies, compared with black patients without anti
      RNP or anti-Sm.

PMID- 10084040
TI  - Low grade fever, back pain and livedo reticularis in a 60-year-old man.

PMID- 10084041
TI  - Valvular deposition of antiphospholipid antibodies in the antiphospholipid
      syndrome: a clue to the origin of the disease.
AB  - In this report we present an unusual case of a 45-year-old female patient with
      systemic lupus erythematosus (SLE) who was hospitalized for mitral valve
      replacement. In her childhood she presented with mitral stenosis and chorea on
      which grounds a preliminary diagnosis of rheumatic fever was established. After a
      quiescent period lasting two decades her disease erupted with mitral stenosis,
      thromboembolic phenomena, and nephritis. Due to severe malfunctioning of her
      mitral valve, the patient eventually underwent mitral valve replacement. The
      antibodies involved in the pathogenesis of our patient's valvular disease were
      studied by immunohistochemical analysis, applying rabbit polyclonal anti-human
      IgG and IgM anti-human C3c and anti-idiotypes to a mouse monoclonal naturally
      occurring polyspecific human monoclonal anti-cardiolipin antibody termed S2.9,
      and to the 16/6 Id which defines a common Id on anti-DNA antibodies in patients
      with SLE. Immunoperoxidase staining using an anti-idiotype mAb to anti
      cardiolipin antibodies demonstrated the deposition of these anti-bodies in the
      subendothelial layer of the valve. We believe that anti-phospholipid syndrome
      (APS) with SLE was the initial and primary disease in this patient. These
      findings clearly indicate that APS must be considered in the differential
      diagnosis of rheumatic fever, particularly in young female patients who present
      with mitral stenosis and chorea.

PMID- 10084042
TI  - Isolated tenosynovitis associated with psoriasis triggered by physical injury.
AB  - A 60-year-old man who had been suffering from psoriasis for 20 years developed
      finger dactylitis and inflammatory swelling with pitting edema over the dorsum of
      the hand one week after a contusive trauma to the left hand. These were not
      followed by any other clinical manifestations of PsA.

PMID- 10084043
TI  - Acitretin and AIDS-related Reiter's disease.
AB  - A patient with AIDS presented with Reiter's syndrome. Arthritis and skin lesions
      responded poorly to nonsteroidal anti-inflammatory drugs and topical
      corticosteroid therapy. Dramatic improvement was seen 2 weeks after acitretine
      was added. When Reiter's syndrome recurred 11 months later despite treatment with
      highly active anti-retroviral drugs and an undetectable plasmatic viral load,
      acitretin without NSAID or topical treatment was again administered and was
      rapidly effective.

PMID- 10084044
TI  - Signal transduction in T lymphocytes.
AB  - T lymphocytes utilize a variety of surface receptors to transmit environmental
      signals across the plasma membrane and initiate biochemical events leading to
      responses such as proliferation, anergy, cytokine secretion, and death. The T
      cell receptor complex, CD28, IL-2 receptor, and CD95 each couple to distinct sets
      of cytoplasmic signaling events to modulate the biological responses of T cells.
      Deficiency or defective function of proteins involved in signaling through these
      receptors are associated with murine and human disease.

PMID- 10084045
TI  - Juvenile dermatomyositis: clinical profile and disease course in 25 patients.
AB  - A retrospective analysis of 25 Arab patients with juvenile dermatomyositis (JDMS)
      was conducted between 1988 and 1996. The mean age at disease onset was 8.25 years
      (range 1.5-15 yrs) with a male: female ratio of 1.5:1. The disease duration
      before diagnosis was 1-108 months. Two patients had a family history of JDMS. The
      clinical features included fever in 14 patients (56%), weight loss in 20 (80%),
      muscle weakness in all 25 (100%), and muscle pain in 14 (56%). Skin lesions
      included Gottron's papules in 15 patients (60%), heliotrope in 13 (52%),
      erythematous malar rash in 8 (32%), and pigmentary changes in 12 (48%). Seventeen
      of the 25 patients had arthralgia (68%) and 16 patients had arthritis (64%).
      Gastrointestinal symptoms were noted in 19 patients (76%). Myocarditis with
      cardiac failure was the initial presentation of 1 patient, while 2 had conduction
      defect. Twelve patients (48%) had respiratory symptoms. The course of the disease
      was complicated by calcinosis in 10 patients (40%). All of the patients were
      treated with prednisone; 15 were also treated with methotrexate. The duration of
      follow up ranged from 6-108 months (mean 54.5 months). Twenty-three patients
      improved, including those who had calcinosis at the time of presentation, with a
      current muscle power of 4/5 in 10 patients (40%) and 5/5 in 13 patients (52%). No
      deaths were reported in our series and no patients are currently bedridden.

PMID- 10084046
TI  - A population-based study on uveitis in juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To obtain information on the occurrence and characteristics of uveitis
      in a population-based survey of patients with juvenile rheumatoid arthritis
      (JRA). METHODS: The subjects in this study were entitled, under the nationwide
      sickness insurance scheme, to receive specially reimbursed medication for JRA in
      5 of the 21 central hospital districts in Finland (population base about 270,000
      children < 16 years of age) in 1980, 1985 and 1990. RESULTS: A total of 114
      incident cases (34 boys and 80 girls) satisfied the criteria for JRA. Uveitis was
      diagnosed in 18 of these patients (16%). The mean age of uveitis patients at the
      diagnosis of JRA was 6.8 years (median 5.4 years) and the mean interval from the
      diagnosis of JRA to the detection of uveitis was 2.9 years. Silent (asymptomatic)
      anterior uveitis was found in 4 boys and 11 girls and acute anterior uveitis in 2
      boys. One girl had marginal corneal ulceration with mild anterior uveitis.
      Uveitis was chronic (> 6 months) in 9 cases. Uveal inflammation was most severe
      in the 3 children whose uveitis was detected at the time of the diagnosis of JRA.
      CONCLUSION: The study provides population-based information on the occurrence and
      characteristics of uveitis associated with JRA.

PMID- 10084047
TI  - Acute lupus myelitis affecting the clonus medullaris.

PMID- 10084048
TI  - Vasculitis and oral and genital ulcers: Behcet's syndrome or HIV infection?

PMID- 10084049
TI  - Highly positive dsDNA antibodies in minocycline-induced lupus.

PMID- 10084050
TI  - Leucocytoclastic vasculitis in a young body builder.

PMID- 10084051
TI  - Human herpesvirus-7 infection in a patient with systemic lupus erythematosus.

PMID- 10084052
TI  - Accelerated nodulosis immediately after initiating weekly low dose methotrexate
      for rheumatoid arthritis.

PMID- 10084053
TI  - Pernicious anemia in a patient with giant cell arteritis in long-term remission.

PMID- 10084054
TI  - "Pray sign" and giant cell arteritis.

PMID- 10084055
TI  - Fourth international workshop on neonatal lupus syndromes and the Ro/SSA-La/SSB
      System.

PMID- 10084056
TI  - Evolution of the diagnosis of acute myocardial infarction.

PMID- 10084057
TI  - New plasminogen activators: a clinical review.
AB  - Rapid restoration of patency of the infarct-related artery is the key to
      preserving myocardium and improving survival. This understanding has led to the
      application of genetic engineering to develop new plasminogen activators with
      specific clinical features. These novel activators may provide faster and more
      complete reperfusion in a greater number of patients, and do so with less risk of
      bleeding and intracranial hemorrhage. This article reviews the pharmacologic
      profiles and clinical performance of several novel plasminogen activators
      engineered from the human tissue plasminogen activator molecule or developed from
      animal and bacterial proteins.

PMID- 10084058
TI  - Enhanced external counterpulsation in the management of patients with
      cardiovascular disease.
AB  - Studies over the past several decades support the hypothesis that enhanced
      external counterpulsation (EECP) can provide long-term benefits in patients with
      angina secondary to chronic coronary disease. Numerous non-sham controlled trials
      have recently been substantiated by a multicenter, randomized trial. Although the
      mechanism by which this mechanical treatment effects an alteration in cellular
      processes within the myocardium remains unclear, recent scientific investigations
      suggest that shear stress induced by chronic exposure to EECP might result in the
      release of a variety of growth factors and the subsequent stimulation of
      angiogenesis in the coronary beds. Ongoing clinical trials in patients with
      significant left ventricular dysfunction, an international registry, and
      additional clinical trials may help to elucidate further the role of this novel
      and unique therapy in our clinical armamentarium.

PMID- 10084059
TI  - Predictors of death and mode of death during long-term follow-up among patients
      with unconfirmed acute myocardial infarction.
AB  - BACKGROUND: Among patients hospitalized with a suspected acute coronary syndrome,
      a minority will eventually develop a confirmed acute myocardial infarction (AMI).
      In the remaining patients, coronary artery disease is the underlying cause in a
      large proportion. HYPOTHESIS: The aim of the study was to determine risk
      indicators for death and the mode of death during 5 years of follow-up among
      patients hospitalized and surviving hospitalization, who presented with initially
      suspected AMI, but in whom infarction was not confirmed. METHODS: Consecutive
      patients who fulfilled the above criteria and were discharged from Sahlgrenska
      Hospital alive during 1986 and 1987 were followed for 5 years. RESULTS: In all,
      1,227 patients, of whom 396 (34%) died during the 5 years of follow-up, fulfilled
      the criteria. The following factors appeared to be independent risk indicators
      for death: age (p < 0.001); male gender (p < 0.001); a history of either current
      smoking (p < 0.001), congestive heart failure (p < 0.01), or myocardial
      infarction (p < 0.05); congestive heart failure during hospital stay (p < 0.01);
      and prescription of digitalis at discharge (p < 0.05). Among patients who died,
      only 63% were judged to have been dying a cardiac death. CONCLUSION: Among
      patients hospitalized with suspected acute coronary syndrome and discharged from
      hospital without a confirmed AMI, one third had died during the 5 years of follow
      up. Risk indicators for death were related to age, male gender, history of
      current smoking, congestive heart failure or previous AMI, congestive heart
      failure in hospital, and digitalis medication at discharge.

PMID- 10084060
TI  - The independent effects of left ventricular ejection fraction on short-term
      outcomes and resource utilization following hospitalization for heart failure.
AB  - BACKGROUND: While depressed left ventricular ejection fraction is clearly
      associated with poor long-term outcome in heart failure (HF), the effect of
      ejection fraction on short-term outcomes and resource utilization following
      hospitalization for HF remains unclear. HYPOTHESIS: We evaluated the independent
      effect of depressed ejection fraction (< or = 40%) on short-term outcomes and
      resource utilization following hospitalization for HF. METHODS: The study
      population included 443 consecutive patients hospitalized for DRG 127 (HF and
      shock) with known ejection fraction. For each patient, we assessed the
      hospitalization cost (1995 US$), length of stay, in-hospital mortality, 30-day
      mortality, and 30-day readmission rates. RESULTS: Despite similar disease
      severity at admission, patients with ejection fraction < or = 40% (Group 1) had
      longer length of stay (4.0 vs. 3.7 days; p = 0.03), a tendency toward higher
      hospitalization cost ($3,054 vs. $2,770; p = 0.08), more readmissions for any
      cause (0.4 vs. 0.3; p = 0.05) and for HF (0.2 vs. 0.1; p = 0.01), but similar in
      hospital (2.5 vs. 2.6%) and 30-day mortality (4.0 vs. 4.6%) compared with
      patients with ejection fraction > 40% (Group 2). In multivariate analyses, Group
      1 patients were more likely to have higher than median hospitalization cost [odds
      ratio (OR) = 1.98; 95% confidence intervals (CI) = 1.02-3.91] and longer than
      median hospital stay (OR = 1.68; CI = 1.08-3.91); they were also more likely to
      be readmitted for any cause (OR = 2.07; CI = 1.15-3.78) or for HF (OR = 5.71; CI
      = 1.64-21.94), and they tended to have a higher 30-day incidence of death or
      readmission (OR = 1.65; CI = 0.96-2.84). CONCLUSIONS: Depressed left ventricular
      ejection fraction is associated with higher resource utilization and readmission
      rates following hospitalization for HF. Greater focus on patients with depressed
      ejection fraction may increase cost savings from HF disease management programs.

PMID- 10084061
TI  - Differences in patients with acute myocardial infarction treated with primary
      angioplasty or thrombolytic therapy. Maximal Individual Therapy in Acute
      Myocardial Infarction (MITRA) Study Group.
AB  - BACKGROUND: Little is known about the differences in patients with acute
      myocardial infarction (AMI) treated with primary angioplasty or intravenous
      thrombolysis in clinical practice. METHODS: In all, 5,906 patients with AMI were
      registered by the Maximal Individual Therapy in Acute Myocardial Infarction
      (MITRA) study. Of these, 491 (8.3%) patients were treated with primary
      angioplasty and 2,817 (47.7%) with intravenous thrombolysis. RESULTS: There were
      only minor differences in baseline characteristics between the two groups.
      Prehospital delay time (median) was longer in the angioplasty group than in the
      thrombolysis group (161 vs. 120, p = 0.001), as was door-to-treatment time (88
      vs. 30 min; p = 0.001). Patients treated with primary angioplasty more often had
      contraindications for thrombolytic therapy (12.9 vs. 6%, p = 0.001) and received
      beta blockers (65 vs. 58.1%, p = 0.004), heparin (98.2 vs. 91.6%, p = 0.001),
      angiotensin-converting enzyme (ACE) inhibitors (64.8 vs. 50%, p = 0.001) and
      "optimal" concomitant medication (56.4 vs. 42.9%, p = 0.001) more often.
      Univariate analysis showed a significant lower incidence of heart failure (5.3
      vs. 16.5%, p = 0.001), postinfarct angina (7.3 vs. 16.4%, p = 0.001), in-hospital
      death (7.9 vs. 11.7%, p = 0.015) and the combined end point (21.6 vs. 40.3%, p =
      0.001) in these patients. Stepwise logistic regression analysis revealed optimal
      concomitant medication [odds ratio (OR) = 0.94, 95% confidence interval (CI):
      0.89-0.98) and the type of revascularization (OR = 0.65, 95% CI: 0.58-0.73) to be
      associated with a significant reduction in the incidence of the combined end
      point. Similar results were obtained in all predefined subgroups. CONCLUSIONS: In
      clinical practice, patients treated with primary angioplasty are more often
      treated with beta blockers and ACE inhibitors than patients treated with
      intravenous thrombolysis. Thus, the selection of patients and the type of
      revascularization contributes to the reduction in mortality, overt heart failure,
      and postinfarct angina in these patients.

PMID- 10084062
TI  - Wavelet transform analysis of heart rate variability during dipyridamole-induced
      myocardial ischemia: relation to angiographic severity and echocardiographic
      dyssynergy.
AB  - BACKGROUND: Analysis of heart rate variability (HRV) is a valuable noninvasive
      method for quantifying autonomic cardiac control in humans and has been utilized
      during dipyridamole echocardiographic test to differentiate positive from
      negative test results. HYPOTHESIS: We aimed to evaluate, by means of HRV
      analysis, the influence of the angiographic severity of coronary artery disease
      on cardiac autonomic control during dipyridamole-induced myocardial ischemia.
      METHODS: We analyzed RR interval variability changes during dipyridamole-induced
      myocardial ischemia in 31 selected patients (mean age 54 +/- 9 years) with
      available coronary angiography and positive dipyridamole echocardiographic test.
      Spectral components of HRV were assessed by means of wavelet transform analysis
      for the last 5 min before the beginning of the test (baseline) and for 5 min
      after the onset of ischemia-related events (peak dipyridamole effect). RESULTS:
      Patients were divided into three groups according to the number of coronary
      diseased vessels (Group A, single-vessel disease; Group B, double-vessel disease;
      Group C, triple-vessel disease). No difference was detectable at baseline among
      the three groups. After dipyridamole, low-frequency power, a measure of
      sympathetic modulation of heart rate, increased and echocardiographic wall motion
      score index worsened in all groups (p < 0.001). The increase in low-frequency
      power was more evident in Group C patients than in the other two groups (p <
      0.005). Furthermore, after dipyridamole, a direct correlation was found between
      low-frequency power and wall motion score index (r = 0.59; p < 0.001).
      CONCLUSIONS: These data suggest that HRV analysis performed during dipyridamole
      echocardiographic test provides useful information to assess the severity of
      coronary artery disease.

PMID- 10084063
TI  - Frequency domain heart rate variability and plasma norepinephrine level in the
      coronary sinus during handgrip exercise.
AB  - BACKGROUND: Heart rate (HR) variability has been recognized as an important
      noninvasive index of autonomic nervous activities. However, the relationship
      between HR variability and cardiac circulating norepinephrine (NE), especially
      with respect to coronary ischemia, remains unclear. HYPOTHESIS: This study was
      undertaken to determine whether HR variability indices can reflect cardiac NE
      levels during handgrip exercise. METHODS: We simultaneously measured HR
      variability and cardiac NE overflow rate in 32 patients (30 men, 2 women) during
      a 6-min isometric handgrip exercise. Among the 32 subjects, 20 (19 men, 1 woman)
      had coronary artery disease (CAD) and 12 (control group; 11 men, 1 woman) did
      not. RESULTS: Hemodynamics and cardiac NE overflow rates among subjects at rest
      were not significantly different between the two groups. In the normal subjects,
      low-frequency (LF) spectra and LF/HF (high-frequency) ratios were not
      significantly changed during handgrip exercise, but HF spectra significantly
      increased from 10.1 +/- 4.5 to 12.2 +/- 7.0 ms (p < 0.05). In the subjects with
      CAD, LF and LF/HF spectra were significantly (p < 0.05 and 0.01, respectively)
      increased by handgrip exercise. High-frequency spectra were not significantly
      changed by handgrip exercise. In the normal subjects, a significant negative
      relation (r = -0.76, p < 0.01) was obtained between HF change and cardiac NE
      overflow rate, whereas this relationship was not significant in the subjects with
      CAD. The correlation between changes of LF/HF and cardiac NE overflow rate was
      significant in the normal (r = 0.56, p < 0.05) but not in subjects with CAD.
      CONCLUSION: These results suggest that vagal modulation of HR variability is more
      prominent in normal coronary artery subjects than in CAD subjects during handgrip
      exercise. Heart rate variability indices may thus serve as adequate indicators of
      autonomic nerve activity in subjects with normal coronary arteries but not in
      those with CAD, probably due to decreased adaptation to physical stress during
      handgrip exercise.

PMID- 10084064
TI  - Efficacy and tolerability of a very low molecular weight heparin compared with
      standard heparin in patients with unstable angina: a pilot study.
AB  - BACKGROUND: Unstable angina is an active thrombotic process that involves
      thrombus formation and platelets. It requires a rapid and intensive treatment
      with anticoagulants and antiplatelets. HYPOTHESIS: The aim of the present study
      was to compare the efficacy of a very low molecular weight heparin, OP 2000, with
      standard heparin in the treatment of unstable angina. Tolerance and safety were
      also assessed. METHODS: The study population included 120 consecutive
      hospitalized patients with unstable angina randomized for treatment with very low
      molecular weight heparin or with standard heparin. The dosage of the study drug
      was 200 mg intramuscular (i.m.) the first day followed by 150 mg IM/day. The
      control drug was standard heparin starting at a dosage of 5,000 UI/ml
      intravenously (i.v.) and followed by continuous infusion at an activated partial
      thromboplastin time-adjusted dosage. The primary end points were death, acute
      myocardial infarction, urgent revascularization, and recurrence of angina.
      Tolerability was assessed using bleeding parameters, thrombocytopenia, and
      allergic reactions. RESULTS: Fourteen clinical events were reported in the study
      group compared with 25 events in the control group (p < 0.05). No adverse events
      were reported in either group. CONCLUSION: During the acute phase of unstable
      angina, treatment with a very low molecular weight heparin plus aspirin was more
      effective than treatment with standard heparin plus aspirin.

PMID- 10084065
TI  - Prevalence of ventricular late potentials in patients with obstructive sleep
      apnea syndrome.
AB  - BACKGROUND: It is known from various cardiac disorders that the presence of
      ventricular late potentials (VLP) in the signal-averaged electrocardiogram (ECG)
      is associated with an increased risk of sudden cardiac death. HYPOTHESIS: In view
      of the increased cardiovascular mortality of patients with obstructive sleep
      apnea syndrome (OSAS), we assessed the prevalence of VLP in these patients.
      METHODS: In all, 118 consecutive patients with polysomnographically verified OSAS
      were prospectively studied; 21 snorers without evidence of a sleep-related
      breathing disorder served as a control group. Signal-averaged ECG and 24-h Holter
      ECG were performed in all patients and controls, and left ventricular function
      was determined by radionuclide ventriculography in the OSAS group. Furthermore,
      patients and controls were followed for up to 45.5 months for arrhythmic events,
      syncopes, or sudden cardiac death. RESULTS: An abnormal signal-averaged ECG was
      seen in seven patients (5.9%) and in one snorer (4.8%). Patients with and without
      VLP did not differ with respect to age, body mass index, left ventricular
      ejection fraction, or ectopic activity in the 24-h Holter ECG, but the former had
      significantly higher mean (standard deviation) apnea/hypopnea indices [55.4
      (25.2)/h vs. 37.4 (22.6)/h; p < 0.05]. Of the 118 patients, 110 could be followed
      for 26.7 (7.9) months. During this period, two patients had syncopes and one
      patient had sudden cardiac death. The seven patients with VLP remained free of
      events during the follow-up period, as did the 21 snorers. CONCLUSIONS: Patients
      with OSAS have a low prevalence of VLP in the signal-averaged ECG, not exceeding
      that in normal subjects. Moreover, abnormal signal-averaged ECGs do not appear to
      be useful as a prognostic marker.

PMID- 10084066
TI  - Electrocardiographic screening for emphysema: the frontal plane P axis.
AB  - BACKGROUND: Because the most characteristic and sensitive electrocardiographic
      (ECG) correlate of pulmonary emphysema in adults is verticalization of the
      frontal plane P-wave vector (P axis), we investigated its strength as a lone
      criterion to screen for obstructive pulmonary disease (OPD) in an adult hospital
      population. METHODS: In all, 954 consecutive unselected ECGs were required to
      yield 100 with P axis > or = +70 degrees (unequivocally negative P in a VL during
      sinus rhythm) and pulmonary function tests. and 100 with P axis < or = +50
      degrees (unequivocally positive P-aVL). RESULTS: Obstructive pulmonary disease by
      both pulmonary function test and clinical criteria was present in 89 of 100
      patients with vertical P axes and 4 of 100 patients without OPD. CONCLUSION: The
      high sensitivity (89% for this series) and high specificity (96%) makes vertical
      P axis a useful screening criterion. Its at-a-glance simplicity makes it "user
      friendly."

PMID- 10084067
TI  - Aortic saddle embolism.

PMID- 10084068
TI  - Intrapericardial Doppler flow signals in cardiac tamponade.

PMID- 10084069
TI  - Reduced left ventricular dimension and normalized atrial natriuretic hormone
      level after repair of aortic coarctation in an adult.
AB  - Although unusual in the older patient, coarctation of the aorta can be an occult
      cause of cardiomyopathy. This report describes a 53-year-old man with new-onset
      heart failure symptoms, global left ventricular (LV) dysfunction, and underlying
      aortic coarctation. Surgical correction resulted in reduced LV size, resolution
      of symptoms, and normalization of atrial natriuretic hormone levels.

PMID- 10084070
TI  - Long-term survival of a patient with left ventricular free wall rupture without
      surgical repair.
AB  - This report describes the case of a patient who developed postinfarction left
      ventricular free wall rupture and cardiac tamponade. He was managed
      conservatively, made a successful recovery, and is alive and asymptomatic 10
      months after the index episode. Only 17 cases in which the patients survived
      subacute rupture of the ventricular free wall over the long term without surgical
      repair have been reported in the literature.

PMID- 10084071
TI  - Utility of thallium-201 scintigraphy in detecting right ventricular dysfunction
      in pulmonary embolism.
AB  - Acute right ventricular dysfunction has been established both as a diagnostic and
      prognostic indicator in pulmonary embolism. This report illustrates the utility
      of thallium-201 scintigraphy as an adjunctive noninvasive test in the diagnosis
      of pulmonary embolism by demonstrating increases in regional right ventricular
      perfusion and its subsequent resolution with treatment presumably as a result of
      decreased pressure work.

PMID- 10084072
TI  - Atrial tamponade causing acute ischemic hepatic injury after cardiac surgery.
AB  - A patient developed late cardiac tamponade after aortic valve replacement and
      coronary artery bypass grafting. Nausea and dramatic elevations of serum
      aminotransferases were the initial clinical manifestations of cardiac tamponade.
      Severe acute ischemic hepatic injury secondary to isolated compression of both
      atrial cavities by two loculated thrombi was diagnosed.

PMID- 10084073
TI  - Myocardial infarction and Turner's syndrome.
AB  - This paper reports the case of a patient with Turner's syndrome, who developed a
      myocardial infarction at the age of 36. Turner's syndrome, associated with
      gonadal insufficiency, increases atherosclerotic cardiovascular risks that must
      be assessed during the patient's follow-up.

PMID- 10084074
TI  - Robert S. Fraser.

PMID- 10084075
TI  - Sensitivity and long-term prognostic value of cardiac troponin I increase shortly
      after percutaneous transluminal coronary angioplasty.

PMID- 10084076
TI  - Update on varicella vaccine.
AB  - A live varicella vaccine has been licensed in Japan, Korea, some European
      countries, and the United States. Susceptible children can receive varicella
      vaccine at 12 to 18 months of age, and those who lack a reliable history of
      chickenpox should be immunized between 11 and 12 years of age. Susceptible
      children 13 years of age or older should receive two doses at least 1 month
      apart. Varicella vaccine administered under routine conditions has been proved to
      be highly effective. Varicella immunization has induced long-term humoral and
      cellular immunity. The varicella vaccine can be given in immunocompromized
      children, including children with leukemia and bone marrow transplantation
      recipients, when immune function recovers. Inactivated varicella vaccine can also
      reduce morbidity due to varicella zoster virus reactivation in high-risk
      populations.

PMID- 10084077
TI  - The rotavirus vaccine.
AB  - A rotavirus vaccine was recently licensed by the Food and Drug Administration and
      is likely to be recommended for use in all infants by both the Advisory Committee
      on Immunization Practices and the American Academy of Pediatrics. If used as
      recommended, the vaccine is likely to prevent much of the 500,000 physician
      visits, 50,000 hospitalizations, and 20 to 40 deaths caused by rotavirus
      infections every year in the United States. An understanding of the biology,
      immunology, and pathogenesis of rotavirus infection will help to explain the
      strengths and limitations of the rotavirus vaccine.

PMID- 10084078
TI  - Pediatric combination vaccines.
AB  - There will be an increasing demand for safe and effective combination vaccines as
      more paediatric vaccines are developed and licensed for new indications. The
      successful introduction of new combination vaccines into the childhood
      immunization schedule has the potential to improve vaccine coverage and thus
      reduce morbidity and mortality from childhood infections, and also possibly to
      reduce the cost of vaccines and their delivery. This article reviews the recent
      literature regarding new combination vaccines and discusses the main issues
      surrounding the simultaneous administration of multiple vaccine antigens to
      children.

PMID- 10084079
TI  - Advances in antiviral therapy.
AB  - Multiple agents for the treatment and prevention of viral illnesses have been
      developed during the past few years. While in many cases this has been in direct
      response to the human immunodeficiency virus type 1 epidemic, a number of new
      antiviral agents are relevant to the practice of general pediatrics. This article
      reviews recent advances in the therapy of some common and a few unusual viral
      illnesses of children. The indication and efficacy of the newly developed agents
      valacyclovir, famciclovir, cidofovir, oral and intraocular ganciclovir, adefovir,
      respiratory syncytial virus immune globulin, palivizumab, and imiquimod are
      discussed, as well new uses of acyclovir, lamivudine, and ribavirin. Many of the
      antivirals discussed, including valacyclovir and cidofovir, have not yet been
      studied in children, but they hold promise for improving the treatment of
      pediatric viral infections.

PMID- 10084080
TI  - Lethargy from an unsuspected culprit.

PMID- 10084081
TI  - Hematology and oncology.

PMID- 10084082
TI  - Biology and clinical significance of the TEL/AML1 rearrangement.
AB  - The accurate identification of chromosomal abnormalities in patients with
      leukemia is essential for diagnosis and treatment assignment. Recent technical
      improvements in the detection of such aberrations have demonstrated that the
      previously unrecognized chromosomal translocation t(12;21) is the most prevalent
      structural aberration in childhood acute lymphoblastic leukemia. Both genes
      involved, translocation ets like gene (or ETV6) on chromosome 12 and acute
      myeloid leukemia 1 gene (or CBF alpha) on chromosome 21 had been identified for
      several years previously, which facilitated the rapid development of molecular
      diagnostic assays and their implementation in therapy trials. Although first
      described less than four years ago, the TEL/AML1 story is an excellent example of
      how close collaboration between physicians and molecular biologists is mandatory
      for achieving general insights into the molecular pathogenesis of leukemia and
      for further improvements in diagnosis and in monitoring response to chemotherapy.

PMID- 10084083
TI  - Innovative therapies for pediatric brain tumors.
AB  - Success in the treatment of pediatric brain tumors has lagged behind that of
      other pediatric cancers. This paper highlights many of the advances that have
      taken place over the past few years in the surgical, radiotherapeutic, and
      chemotherapeutic approaches to central nervous system lesions that we hope will
      lead to a dramatic improvement in outcome. Innovations in neurosurgical and
      radiotherapeutic techniques have resulted in decreasing toxicity although
      substantial improvement in cure rates has not been observed. Many new techniques
      such as gene therapy, angiogenesis inhibitors, immunotherapy, and others that
      have not been part of the classic approach to these lesions are now in clinical
      trials in the hope that they will impact on the survival of these patients. The
      scientific basis for these new treatment modalities and preliminary clinical
      results are discussed.

PMID- 10084084
TI  - Treatment of fungal infections in neutropenic children.
AB  - Fungal infections have emerged as one of the most significant complications of
      antineoplastic therapy and marrow transplantation in children. Morbidity and
      mortality associated with fungal infections are high. Recent trends indicate that
      the incidence and spectrum of fungal infections are increasing, partly because of
      the increase in the number of children receiving intensive chemotherapy and
      marrow transplantation, but also because of the successful management of
      bacterial and viral infections. Though many factors may contribute to risk for
      developing a fungal infection, prolonged neutropenia is the most important. Until
      recently, options for antifungal therapy were limited. Advances include less
      toxic formulations of amphotericin B and an expanding armamentarium of azoles as
      well as new antifungal compounds. This review addresses the therapeutic options
      available for treatment of fungal infections in immunocompromised children.

PMID- 10084085
TI  - Antithrombotic therapy in children.
AB  - Thromboembolic events are an increasingly common secondary complication in
      children who are successfully treated for serious, life-threatening primary
      diseases. In contrast to adults, thromboembolic events are rare enough in
      children to hinder clinical trials assessing optimal use of antithrombotic
      agents. Currently, pediatric patients are treated according to guidelines
      extrapolated from adults. However, optimal prevention and treatment of
      thromboembolic events in children likely differs from such treatment for adults.
      The following review summarizes the available information on commonly used
      antithrombotic agents in children, which include standard heparin, low molecular
      heparin, oral anticoagulants, thrombolytic therapy, antiplatelet agents,
      antithrombin concentrates, and protein C concentrates. The mechanisms, dosing,
      monitoring, therapeutic range, factors influencing dose-response relationship,
      and side effects are discussed.

PMID- 10084086
TI  - Orthopedics.

PMID- 10084087
TI  - Ultrasonography and developmental dysplasia of the infant hip.
AB  - Hip sonography has been developed, refined, and critiqued for over 18 years. It
      is now widely accepted as a highly sensitive and useful technique for both the
      diagnosis and management of developmental dysplasia of the infant hip.
      Controversy continues surrounding the issue of when and how often hip sonography
      should be performed. Currently, clinical screening of newborns is the standard of
      care in the United States, with sonography employed selectively based on clinical
      findings. Universal ultrasound screening has been used in some countries and is
      under consideration by many investigators, using a variety of algorithms. This
      review will focus on recent reports dealing with issues of screening for
      developmental dysplasia of the infant hip and also will highlight techniques
      suggested for use in the treatment of development dysplasia of the infant hip.

PMID- 10084088
TI  - Scheuermann's kyphosis.
AB  - Scheuermann's disease is a kyphotic deformity of the spine that develops in early
      adolescence. This condition has been reported to occur in 0.4% to 8% of the
      general population, with an equal distribution between sexes. Diagnosis of
      Scheuermann's disease is suggested on clinical examination; however, parents of
      children affected often confuse it with poor posture. Radiographs are the
      standard imaging modality used to confirm the diagnosis of Scheuermann's disease.
      Classic signs include vertebral end plate irregularity, disk space narrowing, and
      anterior wedging of involved vertebral bodies. Other diagnostic tools such as CT
      scans or magnetic resonance imaging may also be of value in the evaluation of
      Scheuermann's disease. The mode of treatment for this condition depends upon the
      severity of the deformity, remaining growth, and presence or absence of symptoms.
      Early treatment may be limited to observation and exercises, whereas patients who
      have kyphosis of up to 75 degrees and how have growth remaining may benefit from
      bracing. Surgical correction is reserved for severe cases that are symptomatic
      and refractory to conservative management.

PMID- 10084089
TI  - Legg-Calve-Perthes' disease.
AB  - The etiology, radiographic classification, and treatment of Legg-Calve-Perthes'
      disease remain controversial. Several recent papers focus on these issues in an
      effort to provide guidance in the clinical care of Perthes' disease. The research
      studied in this paper lends further support to the hypothesis of clotting
      abnormalities with vascular thrombosis, which seems to be the most likely
      etiology for Legg-Calve-Perthes' disease. Several studies focus on use of
      magnetic resonance imaging for the early diagnosis and prognosis of Perthes'
      disease. A few researchers whose work is featured in this paper add information
      on the treatment of Perthes' disease, supporting surgical treatment for older
      patients with more severe disease and non-surgical treatment for younger patients
      with less extensive femoral head involvement.

PMID- 10084090
TI  - Diagnosis and treatment of slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis remains a diagnostic problem despite numerous
      papers written on the subject. The most important factor in the diagnosis of
      slipped capital femoral epiphysis is suspicion by the practitioner. The history,
      physical examination, and radiographic imaging are important in the confirmation
      of the diagnosis. Imaging is the topic of 1998 with advances in the areas of
      ultrasound. Ultrasound may be better in experienced hands than plain radiography
      in the diagnosis of slipped capital femoral epiphysis. Magnetic resonance imaging
      is used for diagnosis of slipped capital femoral epiphysis and in the assessment
      of pre-slips. The magnetic resonance image can be oriented to a plane orthoganol
      to the plane of the physis to assess the width of the physis and to detect edema
      in the area of the physis.

PMID- 10084091
TI  - The young athlete.
AB  - Youth sports are becoming increasingly popular in America. Previous studies have
      shown that children and adolescents are not small adults in their response to
      exercise and stress. Intensive competition and training may be associated with
      acute and chronic illness and injury. In addition, we comment on the injury risks
      that are generated by pressures to perform, injuries from urbanized non-team
      sports, and legislation underway to minimize these injuries. We also provide
      insight into psychological and sociological trends in the pediatric athlete and
      discuss the roles of the pediatrician, coach, trainer, and parent and the ways in
      which these roles impact upon injury and prevention in this population.

PMID- 10084092
TI  - Fever without apparent source on clinical examination, lower respiratory
      infections in children, and other infectious diseases.
AB  - This section focuses on issues in infectious disease that are commonly
      encountered in pediatric office practice. Paul McCarthy discusses recent
      literature regarding the evaluation and management of acute fevers without
      apparent source on clinical examination in infants and children and the
      evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews
      recent literature about lower respiratory tract infection in children. Finally,
      Jeffrey Kahn discusses recent developments concerning rotavirus vaccine.

PMID- 10084093
TI  - Restricted spinal anaesthesia for ambulatory surgery: a pilot study.
AB  - The increasing use of ambulatory surgery requires methods of anaesthesia that
      allow patients to be discharged soon after the operation is completed. Spinal
      anaesthesia is usually simple and quick, and the incidence of post-spinal
      headache has been reduced by using non-cutting small-gauge needles. Limiting the
      spread of spinal anaesthesia, as long as it still provides analgesia for surgery,
      should reduce the haemodynamic effects and speed recovery. Restricted spinal
      anaesthesia, intended to be unilateral using 0.18% hypobaric bupivacaine via a
      25G or 27G Whitacre unidirectional needle, was compared with epidural anaesthesia
      (using a mixture of lignocaine and prilocaine) in 64 matched-pair patients
      undergoing ambulatory arthroscopy. Motor blockade, assessed for the specific
      myotomes L2 to S1, was significantly more unilateral in the spinal group. Two
      patients in the spinal group and nine patients in the epidural group were treated
      for hypotension (P < 0.05). One patient in the spinal group developed a post
      spinal headache. One patient in the epidural group rated the anaesthesia poor.

PMID- 10084094
TI  - Comparison of the effects of topical lignocaine spray applied before or after
      induction of anaesthesia on the pressor response to direct laryngoscopy and
      intubation.
AB  - In an attempt to attenuate the cardiovascular pressor response to laryngoscopy
      and intubation, 30 patients presenting for routine ophthalmic surgery were
      studied and were randomly allocated into two groups: group A (n = 15) received
      direct laryngeal/tracheal lignocaine spray immediately before intubation; and
      group B (n = 15) received orolaryngeal lignocaine spray before the induction of
      anaesthesia. In both groups, general anaesthesia was induced with thiopentone 3-5
      mg kg-1, followed by atracurium 0.6 mg kg-1 to facilitate tracheal intubation.
      Laryngoscopy and endotracheal intubation caused a significant increase in heart
      rate, by 28% in group A and 23% in group B (P < 0.05 in both), and in diastolic
      blood pressure, by 28% in group A and 24% in group B (P < 0.05 in both). In group
      A, the systolic blood pressure also increased significantly (by 18%) after
      intubation, but there was no significant change in group B. In addition, the
      plasma lignocaine concentrations remained well below the toxic range in both
      groups. It was concluded that topical lignocaine administration as an
      orolaryngeal spray before the induction of anaesthesia is effective in reducing
      but not abolishing the pressor response to laryngoscopy and endotracheal
      intubation.

PMID- 10084095
TI  - Changes in central venous pressure and pulmonary capillary wedge pressure do not
      indicate changes in right and left heart volume in patients undergoing coronary
      artery bypass surgery.
AB  - The value of pulmonary artery catheterization is a matter for discussion.
      Previous studies suggest that direct measurements of intravascular volume
      distribution and cardiac volume indices may be of greater relevance than central
      venous and pulmonary capillary wedge pressure. We therefore used a thermo-dye
      dilution technique for the quantification of central blood volume, right
      ventricular end-diastolic volume and left heart volume in patients undergoing
      coronary artery bypass surgery. Measurements were performed after the induction
      of anaesthesia as well as 1, 6 and 24 h after surgery. Central venous pressure
      was significantly increased at 1 and 6 h, whereas right ventricular end-diastolic
      volume was increased only at 6 h post-operatively. Pulmonary capillary wedge
      pressure showed a tendency to increase whereas left heart and central blood
      volume decreased significantly after surgery. The results of the present study
      suggest that changes in cardiac filling pressure do not indicate changes in
      indices of cardiac volume in patients after coronary bypass surgery.

PMID- 10084096
TI  - Patient-controlled sedation using propofol: randomized, double-blind dose
      refinement.
AB  - This double-blind, randomized trial compared the onset of sedation with two
      patient-controlled sedation regimens, allowing a maximum of 16 or 25 mg min-1
      propofol. Forty fit young patients presenting for elective surgery were asked to
      try to put themselves to sleep using the system. Onset times of sedative effect,
      slurred speech and amnesia were recorded. All patients achieved satisfactory
      sedation, and none became oversedated. Patients receiving 16 mg min-1 propofol
      were not reliably sedated within 5 min and took significantly longer to develop
      slurred speech and amnesia (P < 0.01 for both). We conclude that this maximum
      infusion rate does not produce amnesia or sedation rapidly enough to be
      clinically useful. A maximum infusion rate of 25 mg min-1 allowed rapid sedation
      in all patients without oversedation and may be an acceptable compromise between
      efficacy and safety.

PMID- 10084097
TI  - Continuous sedation during spinal anaesthesia: gamma-hydroxybutyrate vs.
      propofol.
AB  - Gamma-hydroxybutyrate (GHB) may well be developed as an alternative for optional
      sedation during spinal anaesthesia. As in the case of propofol (PRO), GHB has
      good sedative properties associated with cardiovascular and respiratory
      stability. When used as a narcotic agent, recovery times are variable (e.g. > 30
      min); in contrast, sedative dosages, as used in intensive care patients (e.g. 10
      20 mg kg-1 h-1), result in adequate clinical recovery. The goal of the present
      study was to compare the clinical properties of GHB and PRO after continuous
      administration during spinal anaesthesia (SPA). Thirty patients (ASA I and II)
      received either GHB (n = 15) or PRO (n = 15) at random. Patients refusing
      sedation (n = 15) received 0.9% saline (control). At eight defined time points,
      haemodynamic (BP, HR), respiratory (RR, RMV, PaO2, SpO2, PETO2, PETCO2, VO2,
      VCO2) and endocrinological parameters (plasma concentrations of noradrenaline and
      adrenaline) as well as the clinical side-effects were assessed simultaneously.
      With both sedatives, the desired level of sedation was achieved. Recovery times
      ranged between 1.7 +/- 0.9 min with PRO and 6.1 +/- 4.9 min with GHB. GHB
      provided stable haemodynamic conditions without clinically relevant respiratory
      depression. In contrast, PRO caused a decrease in mean arterial pressure (MAP) of
      15%, whereas respiratory minute volume was decreased by 53% (with periods of
      apnoea, SpO2 < 90%). VO2 and VCO2 correlated with respiratory minute volume (GHB,
      PRO, control). Plasma noradrenaline and adrenaline concentrations remained nearly
      constant in the GHB and control groups and declined during sedation with PRO.
      Both GHB and PRO are suitable for optional sedation during spinal anaesthesia.
      Control and recovery are acceptable for clinical purposes. It seems that GHB and
      PRO have similar haemodynamic, respiratory and endocrinological characteristics.
      Therefore, GHB may serve as an alternative for the established management of
      continuous sedation during SPA with PRO.

PMID- 10084098
TI  - Bispectral index (BIS) monitoring during propofol-induced sedation and
      anaesthesia.
AB  - One may have to use a monitor of cortical suppression to maintain the optimal
      level of sedation and hypnosis. The bispectral index (BIS), a processed EEG
      parameter, which incorporates coupling along with the frequency and amplitude of
      EEG waveforms, has been proposed as a measure of the pharmacodynamic anaesthetic
      effect on the central nervous system. The numerical value of BIS varies from 0 to
      100 (no cerebral activity to fully awake patient). In order to achieve the
      desired level of propofol sedation or hypnosis, a target concentration of
      propofol at the effect site or in the blood must be delivered. Alternately, one
      may use BIS monitoring to monitor hypnosis or sedation levels or to reflect
      propofol concentrations in the blood. Significant correlations between plasma
      propofol concentrations and BIS values (r = 0.68-0.78) have been reported by many
      investigators. During propofol-induced sedation, BIS values may be maintained
      above 75 to prevent airway obstruction and hypoxia. During propofol intravenous
      anaesthesia, BIS values from 40 to 60 have been proposed to maintain the desired
      level of hypnosis, with values below 50 associated with an insignificant
      probability of recall. However, the major limitation of the BIS monitor (monitor
      of hypnosis) relates to the fact that balanced anaesthesia comprises hypnosis,
      areflexia and analgesia and requires the administration of hypnotic agents,
      muscle relaxants and analgesics to achieve the desired clinical effects.
      Therefore, besides using the BIS value guidelines, one may also consider the
      haemodynamic, autonomic and somatic responses of the patient, the anaesthetic
      technique and the surgical interventions before deriving definite conclusions
      about the overall anaesthetic state of the patient.

PMID- 10084099
TI  - The use of combined suprascapular and circumflex (articular branches) nerve
      blocks in the management of chronic arthritis of the shoulder joint.
AB  - Sixteen patients suffering from rheumatoid or osteoarthritis of the shoulder
      joint were studied. All patients complained of pain and limitation of active
      movement of the shoulder joint. Combined neural blockade of the suprascapular
      nerve (SSNB) and articular branches of the circumflex nerve (ACNB) was carried
      out using 4 mL of 1% prilocaine and 4 mL of 6% aqueous phenol. Following this
      procedure, the mean value for pain intensity decreased by 69% (VASP 2.7) and for
      abduction, adduction and flexion increased by 36-67% over a mean time of 13
      weeks. Functional external and internal rotation of the shoulder joint also
      increased after neural blockade. These findings were significant (P < 0.05).
      Further clinical evaluation of combined SSNB and ACNB in relation to previously
      reported methods of neural blockade of the shoulder joint is warranted using a
      randomized, controlled, comparative study. Conventional power calculations (80%
      power, 5% test) indicate that 17 patients per group would be necessary to detect
      one standard deviation (about 2 VASP) or 64 per group to detect a change of 0.5
      standard deviations.

PMID- 10084100
TI  - Comparison of clonidine 1 microgram kg-1 with morphine 30 micrograms kg-1 for
      post-operative caudal analgesia in children.
AB  - In a prospective randomized study in children, we compared caudal bupivacaine
      clonidine with bupivacaine-morphine to evaluate whether clonidine can be used as
      an alternative to morphine in caudal anaesthesia. Caudal anaesthesia was
      administered in 36 children undergoing orchidopexy, hernia repair or
      circumcision, using 1.5 mL kg-1 bupivacaine 0.18% with either 1 microgram kg-1
      clonidine (group 1) or 30 micrograms kg-1 morphine (group 2). Haemodynamic and
      respiratory parameters, anaesthetic requirements, recovery time and pain score
      were monitored for 24 h. Eleven children in group 1 and nine children in group 2
      did not need any supplementary systemic analgesics throughout the 24-h
      observation period. Mean (+/- SD) duration of analgesia in the remaining patients
      was 6.3 h (+/- 3.3 h) in group 1 and 7.1 h (+/- 3.4 h) in group 2 (P = 0.43).
      Recovery time after anaesthesia was significantly longer in group 1 (16.6 +/- 8.8
      min) than in group 2 (11.5 +/- 4.7 min) (P < 0.05). We conclude that analgesia
      provided by 1 microgram kg-1 clonidine added to caudal bupivacaine is comparable
      with that provided by 30 micrograms kg-1 caudal morphine with bupivacaine.
      Clonidine at this low dose did not cause respiratory depression.

PMID- 10084101
TI  - Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and
      median frequency during propofol infusion with or without fentanyl.
AB  - Hypnotic endpoints and/or EEG variables, e.g. bispectral index, 95% spectral edge
      frequency and median frequency, have been studied to monitor anaesthetic
      (hypnotic) depth during total intravenous anaesthesia. In this study, the
      relation between the hypnotic endpoints of unresponsiveness to verbal commands,
      loss of eyelash reflex and body movement response to mechanical nasal membrane
      stimulation vs. bispectral index, 95% spectral edge frequency and median
      frequency during propofol anaesthesia with or without fentanyl is presented.
      Forty-two patients were randomly assigned to receive either propofol infusion, 30
      mg kg-1 h-1 (n = 22), or propofol infusion, 30 mg kg-1 h-1 + fentanyl bolus, 2
      micrograms kg-1 i.v. (n = 20). Bispectral index, 95% spectral edge frequency and
      median frequency and propofol doses were monitored and recorded at
      unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of
      nasal body movement response. The bispectral index values were significantly
      higher in the propofol + fentanyl compared with the propofol group, i.e. 74.7 +/-
      10.9, 73.1 +/- 10.5 and 47.1 +/- 9.2 vs. 65.8 +/- 9.8, 59.6 +/- 10 and 33.8 +/-
      5.7 at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition
      of nasal body movement response respectively. Doses of propofol for achieving the
      hypnotic endpoints were significantly lower in the propofol + fentanyl compared
      with the propofol group. Plasma propofol concentrations at inhibition of nasal
      body movement response were lower in the propofol + fentanyl compared with the
      propofol group (9.2 +/- 2.0 micrograms mL-1 vs. 14.1 +/- 4.2 micrograms mL-1).
      Our results suggest that fentanyl pretreatment potentiates the effects of
      propofol and achieves the hypnotic endpoints at higher bispectral index values
      and lower propofol doses and concentrations (measured at inhibition of nasal body
      movement response).

PMID- 10084102
TI  - Calculated and measured oxygen consumption in mechanically ventilated surgical
      patients in the early post-operative period.
AB  - Oxygen consumption (VO2) measured by indirect calorimetry (Nellcor-Puritan
      Bennett 7250; Carlsbad, CA, USA) has been compared with VO2 calculated by the
      Fick method in 22 volume-controlled ventilated general surgical patients in the
      early post-operative period. For 198 pairs of measurements, VO2 Fick and VO2
      indirect calorimetry correlated significantly (y = 1.00x - 35.8, P = 0.0001, r =
      0.77). VO2 indirect calorimetry was 212 +/- 32 mL min-1 and VO2 Fick was 177 +/-
      41 mL min-1 (P = 0.0001). The bias was 35 +/- 26 mL min-1. This difference
      represents 16 +/- 13% of the total body VO2. VO2 calculated by the Fick method
      did not accurately predict VO2 measured by indirect calorimetry, and the two
      methods were not interchangeable. VO2 calculated by the Fick method
      underestimated VO2 as measured by indirect calorimetry by a systematic quantity
      that could be attributed, in part, to VO2 of the lung. Indirect calorimetry
      should be the preferred method for measuring total body VO2 in mechanically
      ventilated surgical patients.

PMID- 10084103
TI  - Granisetron reduces post-operative vomiting in children: a dose-ranging study.
AB  - This study was undertaken to determine the minimum effective dose of granisetron,
      5-hydroxytryptamine type 3 receptor antagonist, for the prevention of post
      operative vomiting in children undergoing general inhalational anaesthesia for
      surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 120
      children, ASA physical status I, aged 4-10 years, were assigned to receive
      placebo (saline) or granisetron at three different doses (20 micrograms kg-1, 40
      micrograms kg-1, 100 micrograms kg-1) intravenously immediately after inhalation
      induction of anaesthesia (n = 30 of each). A complete response, defined as no
      emesis and no need for another rescue antiemetic during the first 24 h after
      anaesthesia, occurred in 57% with placebo, 67% with granisetron 20 micrograms kg
      1, 90% with granisetron 40 micrograms kg-1 and 90% with granisetron 100
      micrograms kg-1 respectively (P < 0.05; overall Fisher's exact probability test).
      No clinically important adverse events were observed in any of the groups. Our
      results suggest that granisetron 40 micrograms kg-1 is the minimum effective dose
      for the prevention of emesis after paediatric surgery, and that increasing its
      dose to 100 micrograms kg-1 provides no demonstrable benefit.

PMID- 10084104
TI  - Intraoperative respiratory failure in a patient after treatment with bleomycin:
      previous and current intraoperative exposure to 50% oxygen.
AB  - Patients treated with bleomycin (BLM) are at risk of developing acute respiratory
      distress syndrome (ARDS) post-operatively, and this has been associated with high
      intraoperative concentrations of oxygen. We report progressive arterial
      desaturation noticeable 2 h after the start of a 4-h radical neck dissection for
      which the anaesthesia included 50% O2 in N2O. The patient had received two
      courses of bleomycin within the previous 2 months and had undergone an uneventful
      right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks
      previously. His pulmonary function tests before the second procedure showed a
      slight depression of diffusing capacity (DLco) to 80% of predicted and minimal
      airway obstruction consistent with his history of smoking. The pulse oximetric
      reading during his second procedure reached 75%, but rose to 95% after treatment
      with methylprednisolone salbutamol and inspired O2 concentrations between 80% and
      100%. By the end of the procedure, he satisfied the criteria for ARDS and was
      transferred to the ICU, where he developed bilateral pneumonia, deteriorated and
      died of multiple organ failure. This case suggests that the risk of hyperoxic
      pulmonary damage in patients exposed to bleomycin may increase not only with the
      degree and duration of hyperoxia in a given exposure, but also with the latent
      effects of recent previous exposure. Near normality of pulmonary function tests
      cannot be taken as reassurance, and small changes may have more adverse
      prognostic significance than in patients who have not been exposed to bleomycin.

PMID- 10084105
TI  - Malpositioning of the central venous catheter necessitating sternotomy.
AB  - Complication during a drum catheter placement via an antecubital fossa vein is
      presented.

PMID- 10084106
TI  - Allelic discrimination using fluorogenic probes and the 5' nuclease assay.
AB  - Large-scale screening for known polymorphisms will require techniques with few
      steps and the ability to automate each of these steps. In this regard, the 5'
      nuclease, or TaqMan, PCR assay is especially attractive. A fluorogenic probe,
      consisting of an oligonucleotide labeled with both a fluorescent reporter dye and
      a quencher dye, is included in a typical PCR. Amplification of the probe-specific
      product causes cleavage of the probe, generating an increase in reporter
      fluorescence. By using different reporter dyes, cleavage of allele-specific
      probes can be detected in a single PCR. The 5' nuclease assay has been
      successfully used to discriminate alleles that differ by a single base
      substitution. Guidelines have been developed so that an assay for any single
      nucleotide polymorphism (SNP) can be quickly designed and implemented. All assays
      are performed using a single reaction buffer and single thermocycling protocol.
      Furthermore, a standard method of analysis has been developed that enables
      automated genotype determination. Applications of this assay have included typing
      a number of polymorphisms in human drug metabolism genes.

PMID- 10084107
TI  - Multiplex detection of single-nucleotide variations using molecular beacons.
AB  - We demonstrate that single-nucleotide differences in a DNA sequence can be
      detected in homogeneous assays using molecular beacons. In this method, the
      region surrounding the site of a sequence variation is amplified in a polymerase
      chain reaction and the identity of the variant nucleotide is determined by
      observing which of four differently colored molecular beacons binds to the
      amplification product. Each of the molecular beacons is perfectly complementary
      to one variant of the target sequence and each is labeled with a different
      fluorophore. To demonstrate the specificity of these assays, we prepared four
      template DNAs that only differed from one another by the identity of the
      nucleotide at one position. Four amplification reactions were prepared, each
      containing all four molecular beacons, but each initiated with only one of the
      four template DNAs. The results show that in each reaction a fluorogenic response
      was elicited from the molecular beacon that was perfectly complementary to the
      amplified DNA, but not from the three molecular beacons whose probe sequence
      mismatched the target sequence. The color of the fluorescence that appeared in
      each tube during the course of the amplification indicated which nucleotide was
      present at the site of variation. These results demonstrate the extraordinary
      specificity of molecular beacons. Furthermore, the results illustrate how the
      ability to label molecular beacons with differently colored fluorophores enables
      simple multiplex assays to be carried out for genetic analysis.

PMID- 10084108
TI  - Homogeneous genotyping assays for single nucleotide polymorphisms with
      fluorescence resonance energy transfer detection.
AB  - A homogeneous detection mechanism based on fluorescence resonance energy transfer
      (FRET) has been developed for two DNA diagnostic tests. In the template-directed
      dye-terminator incorporation (TDI) assay, a donor dye-labeled primer is extended
      by DNA polymerase using allele-specific, acceptor dye-labeled ddNTPs. In the dye
      labeled oligonucleotide ligation (DOL) assay, a donor dye-labeled common probe is
      joined to an allele-specific, acceptor dye-labeled probe by DNA ligase. Once the
      donor and acceptor dyes become part of a new molecule, intramolecular FRET is
      observed over background intermolecular FRET. The rise in FRET, therefore, can be
      used as an index for allele-specific ddNTP incorporation or probe ligation. Real
      time monitoring of FRET greatly increases the sensitivity and reliability of
      these assays. Change in FRET can also be measured by end-point reading when
      appropriate controls are included in the experiment. FRET detection proves to be
      a robust method in homogeneous DNA diagnostic assays.

PMID- 10084109
TI  - Mutation detection by chemical cleavage.
AB  - Detection and amplification of mutations in genes in a cheap, 100% effective
      manner is a major objective in modern molecular genetics. This ideal is some way
      away and many methods are used each of which have their own particular advantages
      and disadvantages. Sequencing is often thought of as the 'gold standard' for
      mutation detection. This perception is distorted due to the fact that this is the
      ONLY method of mutation identification but this does not mean it is the best for
      mutation detection. The fact that many scanning methods detect 5-10% of mutant
      molecules in a wild type environment immediately indicates these methods are
      advantageous over sequencing. One such method, the Chemical Cleavage method, is
      able to cut the costs of detecting a mutation on order of magnitude and
      guarantees mutation detection as evidenced by track record and the fact that each
      mutation has two chances of being detected.

PMID- 10084110
TI  - Glycosylase mediated polymorphism detection (GMPD)--a novel process for genetic
      analysis.
AB  - A process for mutation and polymorphism detection is described here that offers
      significant advances over current mutation detection systems and that has the
      potential to significantly enhance molecular genetic analysis of human disease.
      This novel process is referred to as glycosylase mediated polymorphism detection
      (GMPD) and exploits the use of highly specific DNA glycosylase enzymes to excise
      substrate bases incorporated into amplified DNA. Action of the glycosylase leaves
      the DNA with one or more specific abasic sites which can be cleaved by enzymatic
      or chemical means. The GMPD process permits detection of polymorphisms and
      mutations using fragment size analysis or solid phase formats. GMPD is
      particularly suitable for genotyping of single nucleotide polymorphism (SNP)
      based markers and also permits efficient scanning of genes for unknown
      polymorphisms and mutations.

PMID- 10084111
TI  - Discrimination of DNA duplexes with matched and mismatched tandem repeats by T4
      endonuclease VII.
AB  - A simple in situ method for scoring short tandem DNA repeat length has been
      developed using T4 endonuclease VII. This method measures tandem repeated simple
      sequences embedded in unique sequences. Single-stranded loops are formed on
      duplexes containing mismatched (different) numbers of tandem repeats. No single
      stranded loops are formed on structures containing matched (identical) numbers of
      tandem repeats. The matched and mismatched loop structures were distinguished and
      differentially labeled by enzymatic treatment with T4 endonuclease VII.

PMID- 10084113
TI  - High-throughput polymorphism screening and genotyping with high-density
      oligonucleotide arrays.
AB  - A highly reliable and efficient technology has been developed for high-throughput
      DNA polymorphism screening and large-scale genotyping. Photolithographic
      synthesis has been used to generate miniaturized, high-density oligonucleotide
      arrays. Dedicated instrumentation and software have been developed for array
      hybridization, fluorescent detection, and data acquisition and analysis. Specific
      oligonucleotide probe arrays have been designed to rapidly screen human STSs,
      known genes and full-length cDNAs. This has led to the identification of several
      thousand biallelic single-nucleotide polymorphisms (SNPs). Meanwhile, a rapid and
      robust method has been developed for genotyping these SNPs using oligonucleotide
      arrays. Each allele of an SNP marker is represented on the array by a set of
      perfect match and mismatch probes. Prototype genotyping chips have been produced
      to detect 400, 600 and 3000 of these SNPs. Based on the preliminary results,
      using oligonucleotide arrays to genotype several thousand polymorphic loci
      simultaneously appears feasible.

PMID- 10084112
TI  - Enzymatic methods for mutation scanning.
AB  - Enzymatic methods for mutation scanning still lack the sensitivity and
      specificity of the chemical cleavage of mismatch method. However developments in
      our understanding of the mismatch recognition process should lead to
      improvements. Several promising candidates exist with potential for more specific
      and sensitive mutation detection.

PMID- 10084114
TI  - Recent enhancements in SSCP.
AB  - High sensitivity, robustness and scalability are the three criteria which
      influence whether techniques for rapid mutation detection will be used in the
      future. PCR-SSCP, one of the most popular methods for detecting mutation,
      especially in the field of medical genetics, is being improved (1) to efficiently
      detect mutations in long stretches of PCR products; (2) to simplify data
      interpretation by removing PCR artifacts and (3) to minimize human involvement in
      the process of mutation detection by a simple post-PCR fluorescence labeling
      followed by separation using automated DNA sequencers.

PMID- 10084115
TI  - Microplate array diagonal gel electrophoresis (MADGE), CpG-PCR and temporal
      thermal ramp-MADGE (Melt-MADGE) for single nucleotide analyses in populations.
AB  - Important requirements for molecular genetic epidemiological studies are economy,
      sample parallelism, convenience of setup and accessibility, goals inadequately
      met by existent approaches. We invented microplate array diagonal gel
      electrophoresis (MADGE) to gain simultaneously the advantages of simple setup, 96
      well microplate compatibility, horizontal electrophoresis, and the resolution of
      polyacrylamide. At essentially no equipment cost (one simple plastic gel former),
      10-100-fold savings on time for sample coding, liquid transfers, and data
      documentation, in addition to volume reductions and gel re-use, can be achieved.
      MADGE is compatible with ARMS, restriction analysis and other pattern analyses.
      CpG-PCR is a general PCR approach to CpG sites (10-20% of all human single base
      variation): both primers have 3' T, and are abutted to the CpG, forcing a TaqI
      restriction site if the CpG is intact. Typically, a 52 bp PCR product is then cut
      in half. CpG-PCR also illustrates that PAGE-MADGE readily permits analysis of
      'ultrashort' PCRs. Melt-MADGE employs real-time-variable-temperature
      electrophoresis to examine duplex mobility during melting, achieving DGGE-like de
      novo, mutation scanning, but with the conveniences of arbitrary programmability,
      MADGE compatibility and short run time. This suite of methods enhances our
      capability to type or scan thousands of samples simultaneously, by 10-100-fold.

PMID- 10084116
TI  - Design and application of 2-D DGGE-based gene mutational scanning tests.
AB  - Currently, there is a need for practical, accurate and cost-efficient tests to
      comprehensively scan human genes for disease-related DNA sequence variation. Two
      dimensional gene scanning (TDGS) is a parallel mutation detection system, based
      on a combination of extensive multiplex PCR amplification ('PCR megaplex') and
      two-dimensional (2-D) DNA electrophoresis. The latter comprises a size separation
      step followed by denaturing gradient gel electrophoresis (DGGE), and allows
      single base pair changes to be distinguished among multiple DNA fragments in
      parallel. Here, we describe the rapid design of TDGS tests and its application to
      mutation identification in several large human cancer genes.

PMID- 10084117
TI  - Differential sequencing with mass spectrometry.
AB  - Differential or genetic sequencing requires searching sample DNA for variations
      with respect to a reference sequence. Conventional detection techniques are too
      labor and cost expensive for use in diagnostic applications, therefore new
      technologies will be required. Measurement techniques based on mass spectrometry
      (MS) possess the potential for high-throughput, high fidelity measurement of
      sequence variation. Unambiguous detection of polymorphic sequences has been
      demonstrated, even in heterozygous samples. Automated reproducible measurements
      of microscopic arrays of samples will enable the high-throughput detection
      required for large-scale applications. Computational simulation and analysis of
      experimental parameters prior to experimentation will provide the optimization
      necessary for development of robust, reproducible measurements.

PMID- 10084118
TI  - Application of constant denaturant capillary electrophoresis (CDCE) to mutation
      detection in humans.
AB  - Constant denaturant electrophoresis is a DNA separation technique based on the
      principle of cooperative melting equilibrium. DNA sequences with distinct high
      and low melting domains can be utilized to separate and identify molecules
      differing by only one base pair in the lower melting domain. Combined with
      capillary gel electrophoresis and when coupled with high fidelity DNA
      amplification, this approach can detect mutants at a fraction of 10(-6).
      Modifications to the capillary electrophoretic system have also increased DNA
      loading capacity which allows for analysis of rare mutations in a large,
      heterogeneous population such as DNA samples derived from human tissues.
      Employment of this technology has determined the first mutational spectrum in
      human cells and tissues in a mitochondrial sequence without phenotypic selection
      of mutants.

PMID- 10084119
TI  - Sources of bias in the detection and reporting of p53 mutations in human cancer:
      analysis of the IARC p53 mutation database.
AB  - p53 gene encodes a transcription factor with tumor suppressive properties and to
      date, somatic mutation of this gene is the most common genetic event in human
      cancer. A relational database has been developed to facilitate the retrieval and
      analysis of these mutations at the International Agency for Research on Cancer
      (IARC) and it currently contains information on over 8000 individual tumors and
      cell lines. Many factors may influence the detection and reporting of mutations,
      including selection of tumor samples, study design, choice of methods, and
      quality control. There is also concern that several biases may affect the way
      data appear in the literature. Minimizing these biases is an essential
      methodological issue in the development of mutation data-bases. In this paper, we
      review and discuss these main sources of bias and make recommendations to authors
      in order to minimize bias in mutation detection and reporting.

PMID- 10084120
TI  - A polymerase chain reaction-based screening method for transgenic Arabidopsis.
AB  - A simple and rapid PCR-based method for screening transformed Arabidopsis plants
      has been developed. Based on the quantity of chlorophyll present in a protoplast
      suspension, the optimal amount of template is calculated and a fragment of the
      transgene is amplified.

PMID- 10084121
TI  - Structures of primer-template hybrids in arbitrarily primed polymerase chain
      reaction.
AB  - Nucleotide sequence analysis of arbitrarily primed PCR products from two known
      regions of human genome revealed that at least six contiguous bases at the 3'-end
      of a primer of 20 bases, were perfectly matched in the primer-template hybrids.

PMID- 10084122
TI  - Cloning and nucleotide sequencing of the secA gene from coryneform bacteria.
AB  - Taking advantage of highly conserved domains present in the secA gene from
      Escherichia coli and Bacillus subtilis, we designed degenerate oligonucleotides
      (oligos) corresponding to these regions. These oligos were used as primers in PCR
      in order to amplify DNA sequences from Brevibacterium flavum MJ233 chromosomal
      DNA. The PCR product was used as a probe to recover genomic fragments from a
      lambda library of Br. flavum MJ233. The complete nucleotide sequence (nt) of the
      cloned 5.3-kb EcoR1 fragment containing the secA homolog from Br. flavum MJ233
      indicated that the deduced gene product of the Br. flavum secA homolog is
      composed of 845 amino acids (aa) with a deduced molecular weight (MW) of 95429.
      Comparison of this aa sequence to the corresponding sequences from E. coli and B.
      subtilis revealed a high degree of conservation and suggested that the Br. flavum
      secA homolog has putative ATP binding regions.

PMID- 10084123
TI  - cDNA cloning and sequence analysis of Lys-49 phospholipase A2 from Agkistrodon
      acutus.
AB  - Total RNA was extracted from venom glands of Agkistrodon acutus. The cDNA
      encoding Lys-49 phospholipase A2 (PLA2) was amplified by reverse transcriptional
      polymerase chain reaction (RT-PCR). The cDNA was cloned into the pGEMT-vector and
      sequenced. The open reading frame (ORF) of Lys-49 PLA2 consists of 414 bp
      encoding 138 amino acids, which includes a signal peptide of 16 amino acids and a
      matured peptide of 122 amino acids. It shows 76% identity in amino acids with
      another reported Lys-49 PLA2. Because residue 49 in mature peptide is Lysine, it
      probably possesses myotoxicity. These results indicate there are at least two
      kinds of myotoxin in the venom of A. acutus.

PMID- 10084124
TI  - The properties of human DNA fingerprints produced by polymeric monocore probes
      (PMC probes).
AB  - The properties of human DNA fingerprints detected by multilocus polymeric
      monocore probes (PMC probes) have been investigated. The PMC probes were produced
      by the polymerase chain reaction with two partly complementary oligonucleotides
      homologous to various minisatellite or microsatellite core sequences (Ijdo J,
      Wells RA, Baldini A, Reeders ST. Nucleic Acids Res 1991;19:4780). It has been
      shown that these probes possess increased sensitivity, they detect considerably
      more hypervariable fragments in genomic DNA thus exhibiting advantages over the
      corresponding oligonucleotides and natural polycore minisatellite probes.
      Variation in the DNA fingerprints of different individuals produced by these
      probes indicates that the probability of accidental identity is very low (< 10(
      12)). According to the data of cross-hybridization with PMC probes of various
      specificity, several distinct families can be distinguished among G-rich
      hypervariable sequences of the human genome.

PMID- 10084125
TI  - Detection of trinucleotide expansion in neurodegenerative disease by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Genotyping of the dentatorubral-pallidoluysian atrophy (DRPLA) locus in six
      patient samples, representing four normal individuals and two DRPLA patients, was
      successfully obtained using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS). DRPLA is a dominantly inherited
      neurodegenerative disorder associated with the expansion of an unstable
      trinucleotide (CAG) repeat. The accurate determination of repeat length utilizing
      MALDI supports the use of this methodology for the analysis of genes containing
      unstable CAG trinucleotide repeats.

PMID- 10084126
TI  - Is the AMCA ready for the new millennium?

PMID- 10084127
TI  - Ultrastructure of the eggs of Culicoides molestus (Diptera: Ceratopogonidae).
AB  - The eggs of Culicoides molestus (Skuse) are described and illustrated by scanning
      and transmission electron microscopy. Eggs are elongate with a slight
      dorsoventral curvature. No outer chorionic tubercles are present. Aeropyles are
      present in large numbers at the anterior end and in lower numbers at the
      posterior end and lateral regions. The chorion has 5 layers. An outer, rough,
      proteinaceous layer covers a smoother inner surface, which in turn encloses a
      layer of columns and meshwork that appears capable of containing air. These
      columns are underlain by an additional 2 layers. The aeropylar region, in
      combination with the chorionic meshwork, appears to provide a plastron that may
      aid in the survival and development of inundated eggs.

PMID- 10084128
TI  - Colonization of Anopheles pseudopunctipennis from Mexico.
AB  - Two colonies of Anopheles pseudopunctipennis, Tapachula and Abasolo strains, were
      established under laboratory conditions with a thermoperiod (29 degrees C during
      the day; 24 degrees C during the night) and artificial dusk. To stimulate mating,
      a light beam from a flashlight was shone on the cage shortly after lights off.
      This procedure was repeated for the first 6 mosquito generations (parental to F6)
      and thereafter light stimulation was unnecessary for mating. The Tapachula colony
      has been maintained for 24 generations in 24 months, with insemination rates in
      females > 80% since the F3, and a monthly production of 30,000 pupae since the
      F7. Using the same procedure, the Abasolo colony from northeastern Mexico has
      been maintained for 13 generations in 14 months, with insemination rates of 26
      52%.

PMID- 10084129
TI  - Analysis of composition of sugar meals of wild mosquitoes by gas chromatography.
AB  - Gas chromatography (GC) was successfully used for the first time to determine the
      components of natural sugar meals in individual mosquitoes and to determine
      whether carbohydrases are present in the crops of these insects. Crops of wild
      mosquitoes collected from a 2-ha cypress swamp north of Gainesville, FL,
      contained fructose, glucose, sucrose, maltose, turanose, melibiose, erlose,
      melezitose, raffinose, and a few unidentified carbohydrates. Time course studies
      with male and female Aedes albopictus showed rapid hydrolysis (> 90%) of sucrose
      occurring within 2 h of ingestion, whereas melezitose remained relatively
      unchanged even 8 h after ingestion. The crop extraction/GC analysis technique is
      an improvement over the cold anthrone test traditionally used for sugar analysis.
      This procedure is a rapid one-step process used to determine natural sugar
      sources, hydrolysis, occurrence, and preferences for individual wild sugar
      feeding Diptera.

PMID- 10084130
TI  - Variation in acid hydrolase enzyme titers in different developmental stages of
      Aedes togoi.
AB  - Genetic mechanisms of filarial nematode susceptibility were studied in Aedes
      togoi. Acid hydrolases may play an important role in this process, including
      humoral or cell-mediated defenses. Levels of acid phosphatase, alpha-glucosidase,
      beta-glucuronidase, and N-acetyl-beta-glucosaminidase were determined for 1st-
      and 4th-instar larvae, male and female pupae, and 1- and 7-day-old adults using
      fluorometric and colorimetric assays. Acid phosphatase activity was highest in 1
      day-old adults, moderate in larvae and pupae, and lowest in 7-day-old adults.
      Female 7-day-old adults had significantly higher levels than males of the same
      age. Moderate levels of alpha-glucosidase were found in larvae, with progressive
      increases in activity from pupae to 7-day-old adults. Levels in male pupae and 1
      day-old males were higher than in females, but activity was twice as high in 7
      day-old females. Activity of beta-glucuronidase was greater in adults, with
      females showing a 2-fold higher level than males at 7 days. In contrast, N-acetyl
      beta-glucosaminidase activity was highest in 1st- and 4th-instar larvae and 1-day
      old males and females. Activity also was significantly higher in male pupae,
      slightly greater in 1-day-old males, but twice as high in 7-day-old females when
      compared to males of the same age. Results showed significant changes and
      variation in acid hydrolase enzyme titers in the different life stages of Ae.
      togoi. These and other specific acid hydrolases could prove effective in
      monitoring biochemical and genetic changes in mosquito populations.

PMID- 10084131
TI  - A diagnostic polymerase chain reaction assay for species A and D of the Anopheles
      Dirus (Diptera: Culicidae) species complex based on ribosomal DNA second internal
      transcribed spacer sequence.
AB  - A polymerase chain reaction assay based on differences in the internal
      transcribed spacer regions of ribosomal DNA was developed for distinguishing 2
      members of the Anopheles dirus sibling species complex. This assay distinguished
      An. dirus species A from species D by producing diagnostic bands, 374 base pairs
      (bp) in length for species A and 663 bp in length for species D. Both laboratory
      colonies and field collections from Hainan and Yunnan provinces of China were
      identified with 100% accuracy.

PMID- 10084132
TI  - The acetylcholinesterase gene Ace: a diagnostic marker for the Pipiens and
      Quinquefasciatus forms of the Culex pipiens complex.
AB  - The taxonomy of the Culex pipiens complex remains a controversial issue in
      mosquito systematics. Based on morphologic characters, 2 allopatric taxa are
      recognized, namely Cx. pipiens (including the form "molestus") in temperate areas
      and Cx. quinquefasciatus in tropical areas. Here we report on variability at the
      nucleotide level of an acetylcholinesterase gene in several strains and natural
      populations of this species complex. Few polymorphisms were found in coding
      regions within a subspecies but many polymorphisms were observed between
      subspecies in noncoding regions. We describe a method based on a restriction
      enzyme polymorphism in polymerase chain reaction-amplified DNA, in which the
      presence or absence of one restriction site discriminates Cx. pipiens, Cx.
      quinquefasciatus, and their hybrids. This technique reliably discriminates
      mosquitoes from more than 30 worldwide strains or populations. Polymerase chain
      reaction amplification of specific alleles may also be a useful tool for
      characterizing specific alleles of each sibling taxon.

PMID- 10084133
TI  - Isolation and characterization of two novel organophosphate resistance mechanisms
      in Culex pipiens from Cyprus.
AB  - Two novel mechanisms of organophosphate resistance were isolated and
      characterized from a population of Culex pipiens L. from Cyprus. Two strains, one
      expressing the novel, highly active esterases A5 and B5 (strain A5B5-R), and one
      expressing insensitive acetylcholinesterase (strain Ace-R), were developed by
      single pair crosses and selection with temephos and propoxur, respectively. The
      A5B5-R strain demonstrated resistance toward organophosphate insecticides that
      could be suppressed by the esterase inhibitor S,S,S-tributyl phosphorotrithioate
      (DEF). No cross-resistance to carbamates occurred. The Ace-R strain demonstrated
      resistance to organophosphate as well as to carbamate insecticides. Propoxur and
      temephos resistance was not affected by the monooxygenase inhibitor piperonyl
      butoxide or by DEF. The Ace-R strain possessed a novel toxicologic profile as
      well as a unique acetylcholinesterase inhibition pattern. Inheritance of temephos
      or propoxur resistance was codominant in F1 offspring. Backcrosses to a
      susceptible strain in both cases failed to fit a single gene model, suggesting
      that multiple loci may be involved. Combining the A5B5-R and the Ace-R strains
      resulted in high levels of temephos resistance, similar to that of the parents.

PMID- 10084134
TI  - Relative efficacy of synthetic pyrethroid-impregnated fabrics against mosquitoes
      under laboratory conditions.
AB  - The efficacy of synthetic pyrethroid-impregnated fabrics was evaluated against
      Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus, under laboratory
      conditions. Results revealed that delta-methrin was significantly superior in
      comparison to lambdacyhalothrin and cyfluthrin. Results of bioassay tests
      revealed that deltamethrin was 1.5 and 1.9 times more effective than
      lambdacyhalothrin and cyfluthrin, respectively, against An. stephensi exposed to
      cotton fabric treated at 100 g/m2. Deltamethrin was 3.9 and 4.6 times more
      effective against Ae. aegypti and 3.53 and 4.0 times more effective against Cx.
      quinquefasciatus. Of cotton, nylon, polyethylene, and jute fabrics, the cotton
      was the best on the basis of median lethal dose (LD50) and 95% lethal dose (LD90)
      values and persistence of insecticide.

PMID- 10084135
TI  - Selective and conventional house-spraying of DDT and bendiocarb against Anopheles
      pseudopunctipennis in southern Mexico.
AB  - Indoor feeding behaviors and mortalities of Anopheles pseudopunctipennis females
      were evaluated following contact with selective (bands covering mosquitoes'
      preferred resting areas) and full applications of DDT and bendiocarb on indoor
      sprayable surfaces. The DDT residues provoked strong avoidance behavior. To a
      lesser degree, mosquitoes were also repelled by bendiocarb-sprayed surfaces.
      Because of strong irritancy/repellency, unfed mosquitoes were driven outdoors in
      proportionally higher numbers. The resting time on selectively or fully DDT
      sprayed huts was greatly reduced in comparison to bendiocarb-sprayed huts.
      Although unfed mosquitoes tended to rest on non-DDT-sprayed surfaces in the
      selectively treated hut, the man-biting rate was similar with both types of
      treatments. Unfed mosquitoes were repelled less from selectively bendiocarb
      treated surfaces. Similar reductions in postfed resting times were observed on
      all surfaces suggesting that once fed, mosquitoes rested on sprayed surfaces for
      shorter intervals of time. Engorged mosquitoes had normal resting behavior (pre-
      and postspray) within the range of preferred resting heights in both DDT- and
      bendiocarb-sprayed huts, but the proportion of mosquitoes fed in the DDT-treated
      huts was lower. Selective spraying of walls was as effective as spraying the
      complete walls with both insecticides, but DDT was more effective in reducing
      mosquito-human contact. These studies show that by more effectively targeting
      vector behavior, a cost-effective alternative to traditional control techniques
      can be achieved.

PMID- 10084136
TI  - Cyfluthrin (EW 050)-impregnated bednets in a malaria control program in
      Ghassreghand (Baluchistan, Iran).
AB  - In a study carried out in the Ghassreghand Division (Baluchistan, Iran) from
      March through November 1995, efficacy of cyfluthrin-impregnated bednets was
      compared to that of untreated nets, in relation to malaria control. Ten villages
      with a total population of 4,572 and 3 villages with a total population of 1,935
      were used as treatment and control, respectively. The collection, impregnation
      (target dosage of 40 mg active ingredient [AI]/m2), and redistribution of the
      nets (9% nylon, 52% light cotton, 30% medium cotton, and 9% heavy cotton),
      carried out in mid-April, were done by local health workers, supervised by the
      senior research staff. Anopheles culicifacies was considered to be the main
      vector of malaria in the named area. This species is mainly zoophilic,
      endophilic, and exophagic. The initial uptake of the insecticide was lower than
      the target dosage, with high variation (nylon, 12.5 +/- 5.4 mg AI/m2; light
      cotton, 33.3 +/- 26.1 mg AI/m2; medium cotton, 25.9 +/- 20 mg AI/m2; heavy
      cotton, 17.6 +/- 12.5 mg AI/m2). The use of impregnated mosquito nets (used
      primarily outside) had no significant effect on the incidence of malaria. No
      difference was detected in the parasite density of patients with positive slides.
      No significant effect was observed in the parous rate, human blood index, and
      sporozoite rate of anopheline vectors. Only the indoor resting densities of An.
      culicifacies and other malaria vectors were drastically reduced after the
      introduction of the cyfluthrin-impregnated nets into the treatment villages. The
      residual activity of cyfluthrin was lower than expected. The mortality of
      anophelines brought in contact with the treated nets for 3 min in bioassays
      dropped to less than 55% in 3 months. The loss of chemical activity was greatest
      for the light cotton nets, followed by the medium cotton nets. Cyfluthrin-treated
      nets were mildly irritating to host-seeking female anophelines in the laboratory.
      The protective rate of impregnation (all fabric kinds included) in preventing
      female mosquitoes from biting through the impregnated nets was initially 5-6
      times that of the nonimpregnated nets. The study did not detect any significant
      difference between the use of untreated versus impregnated bednets in the
      Ghassreghand area. In planning future medium-scale trials, comparison of new
      compounds and formulations to the more widely used pyrethroids such as permethrin
      and deltamethrin is highly recommended.

PMID- 10084137
TI  - Evaluation of lambdacyhalothrin-impregnated bednets in a malaria endemic area of
      India. Part 1. Implementation and acceptability of the trial.
AB  - In malaria endemic forested villages in Orissa State, India, a 3-year comparison
      of nylon nets treated with lambdacyhalothrin at 25 mg/m2, untreated nets, and no
      nets was carried out. Treated nets retained high insecticidal efficacy for more
      than 7 months. Nets washed after 3 months of use gave 98% kill in a bioassay with
      a 3-min exposure. Based on these bioassays during the first year, nets were later
      reimpregnated at 6-monthly intervals with participation of the users. Compliance
      with the use of nets was good. Eighty-eight percent of nets were usable even
      after 3 years. The main benefits perceived by treated net users were reductions
      in malaria, mosquito bites, head louse infestations, and other nuisance insects.
      The trial was well accepted by the community. Issues related to social marketing
      and promotion of nets are discussed.

PMID- 10084138
TI  - Evaluation of lambdacyhalothrin-impregnated bednets in a malaria endemic area of
      India. Part 2. Impact on malaria vectors.
AB  - In malaria endemic villages of the Indian State of Orissa, the impact of bednets
      treated with lambdacyhalothrin at 25 mg/m2 on malaria vectors was assessed during
      a 3-year intervention trial beginning in May 1990. The main malaria vector was
      Anopheles culicifacies with a small contribution from Anopheles fluviatilis. The
      impregnated bednets caused a significant reduction in vector density as assessed
      by morning indoor resting catches, man-biting rate, light trapping, the
      proportion of females engorged with human blood, and the parity rate as compared
      with villages with untreated or no nets. No statistically significant difference
      was observed in these parameters between the villages with untreated nets or no
      nets. The trial demonstrated that the lambdacyhalothrin-treated nets were highly
      effective against the malaria vectors.

PMID- 10084139
TI  - Evaluation of lambdacyhalothrin-impregnated bednets in a malaria endemic area of
      India. Part 3. Effects on malaria incidence and clinical measures.
AB  - In Indian villages with high malaria endemicity use of nylon bednets treated at
      25 mg/m2 at 6-month intervals for 3 years caused significant reductions in
      malaria incidence, slide positivity rate, slide falciparum rate, annual parasite
      index, and parasite rate in the entire population, as well as reductions in rates
      of splenomegaly and anemia in children. In villages with untreated nets,
      considerable reduction also occurred in these parameters except for the rate of
      splenomegaly. In the village without nets, a relatively small drop occurred in
      the parasite rate and anemia but no change occurred in malaria incidence, and an
      increase occurred in the rate of splenomegaly. The trial thus showed the efficacy
      of impregnated bednets against malaria in the forested hills of Orissa State
      where the existing control strategy based on indoor residual spraying of DDT has
      remained incapable of interrupting malaria transmission.

PMID- 10084140
TI  - Possible utilization of metallic copper to inhibit Aedes Albopictus (Skuse)
      larval development.
AB  - The effect of metallic copper on development of Aedes albopictus was studied in
      the laboratory. Multiwire electric cable was used as a source of metallic copper
      in flower saucers colonized by Ae. albopictus. A linear regression coefficient of
      0.68 was obtained between copper concentration in the water during larval
      development and the relative production of adults. Larval mortality was higher in
      earlier instars with less evident effect on 4th-instar larvae and pupae. The
      effect of copper on larval development time and adult weight in both sexes was
      also observed. The strong algicidal action is presumed to only partially explain
      the effect of metallic copper on Ae. albopictus larvae. A direct toxic effect
      also may be involved. The use of metallic copper is suggested as a practical
      alternative method for preventing development of Ae. albopictus in small
      containers such as flower saucers found in urban areas.

PMID- 10084141
TI  - Field trials of biolarvicide Bacillus thuringiensis var. israelensis strain 164
      and the larvivorous fish Aplocheilus blocki against Anopheles stephensi for
      malaria control in Goa, India.
AB  - Severe outbreaks of malaria occurred in the coastal villages of the Candolim
      Primary Health Centre (PHC) of Goa, India, in 1993 and 1994. These outbreaks were
      associated with accelerated construction activity with an influx of migrant
      laborers. The weekly application of Bacillus thuringiensis var. israelensis
      (B.t.i.) strain 164 at 1 g/m2 and introduction of the indigenous larvivorous fish
      Aplocheilus blocki in major breeding habitats of Anopheles stephensi replaced
      ongoing DDT spraying and pyrethrum fogging in June 1994. The objective of this
      study was to evaluate the effects of B.t.i. and larvivorous fish on An. stephensi
      and subsequent transmission of malaria in the Candolim PHC, Goa, India. In 1995
      the populations of an. stephensi in larger habitats (habitats with immatures: t =
      5.19, P = 0.0017; immature density: t = 3.57, P = 0.007) and smaller habitats
      (habitats with immature: t = 3.86, P = 0.005; immature density: t = 4.93, P =
      0.002) and malaria incidence declined substantially (malaria cases: chi 2 = 712,
      P < 0.001; slide positivity rate: chi 2 = 10.36, P < 0.001; annual parasite
      index; chi 2 = 15.1, P < 0.001), whereas the incidence of malaria continued to
      increase in other nearby towns.

PMID- 10084142
TI  - Acute toxicity of selected pesticides to the Pacific blue-eye, Pseudomugil
      signifer (Pisces).
AB  - Because the larvivorous fish Pseudomugil signifer is native to southeastern
      Queensland and is abundant in shallow estuarine habitats, intertidal marshes,
      wetland habitats, and freshwater streams, it was chosen as an indicator species
      for toxicologic studies with pesticides. Acute toxicity studies with 2
      organophosphorus pesticides (pirimiphos-methyl and temephos) and 3 alternate
      compounds under evaluation for registration in Australia (Bacillus thuringiensis
      var. israelensis, s-methoprene, and pyriproxyfen), were tested in 96-h laboratory
      trials. Pirimiphos-methyl was the most toxic compound, with a median lethal
      concentration (LC50) of 0.091 ppm (0.3 times the estimated field concentration
      [EFC] for a 15-cm-deep pool). Temephos had an LC50 value of 0.594 ppm (9.9 times
      the EFC). Bacillus thuringiensis var. israelensis and pyriproxyfen produced LC50
      values of 6.1 x 10(11) International Toxic Units (477 times the EFC) and 0.854
      ppm (106 times the EFC), respectively. s-Methoprene was the least toxic compound,
      with no mortality recorded at 500 times the EFC.

PMID- 10084143
TI  - Aqua-Reslin droplet analysis.
AB  - Aerosol droplets were collected, counted, and sorted using a laser system, the
      Army Insecticide Measuring System, Teflon-coated slides, and magnesium oxide
      coated slides. All droplets, for each method and replication, were generated by a
      London Aire 1820 or a Leco Model 1600. These data indicate that the Army
      Insecticide Measuring System or Teflon-coated slides are so closely similar to
      the laser that they could effectively be used in the field without an
      overwhelming loss in precision.

PMID- 10084144
TI  - Aberrant South African mosquitoes (Diptera: Culicidae): gynandromorphs and
      morphologic variants.
AB  - Two polar gynandromorphs are described, one of Culex (Culex) neavei Theobald and
      the other of Culex (Culex) pipiens. These are the first gynandromorphs of these 2
      species collected in South Africa. A single variant of Aedes (Stegomyia)
      metallicus and 16 variants of Aedes (Stegomyia) ledgeri are also described, all
      of which have variation in scutal morphology.

PMID- 10084145
TI  - Bacterial control of mosquito larvae: investigation of stability of Bacillus
      thuringiensis var. israelensis and Bacillus sphaericus standard powders.
AB  - Bacillus thuringiensis var. israelensis and Bacillus sphaericus products were
      assayed against their respective reference powders IPS82 and SPH88. Since their
      production in 1982 and 1988, the potency and larvicidal activity of these
      standard powders have been regularly checked on their test insects Aedes aegypti
      (for IPS82) or Culex pipiens (for SPH88). Over the 16-year evaluation period of
      IPS82 and 10-year evaluation period of SPH88, their potencies were considered
      stable. The global mean of each year's mean showed a coefficient of variation of
      less than 20%. Larval rearing was the most important factor in the
      reproducibility of the bioassay, although some variation also originated from the
      person performing the bioassay. This study demonstrated that the SPH88 standard
      could be kept in a stock suspension at 4 degrees C for 3 years without loss of
      potency. Moreover, after 9 years of storage in suspension, only a 2-fold decrease
      in the potency of SPH88 was detected.

PMID- 10084146
TI  - Organophosphate and pyrethroid susceptibilities of Culex salinarius adults from
      Texas and New Jersey.
AB  - Susceptibilities of adults from newly established colonies of Culex salinarius
      from New Jersey and Texas to commonly used mosquito adulticides were assessed
      using the insecticide-coated vial bioassay technique. Females from both colonies
      were similar in their susceptibilities to naled, chlorpyrifos, resmethrin, and
      permethrin. However, females from the New Jersey colony (established from
      collections made in Cape May County, NJ) were found to be 9 times more tolerant
      to malathion than were those from the Texas colony (established from collections
      made in Chambers County, TX), with median lethal concentration values for
      malathion tested against these 2 colonies of 0.70 and 0.08 microgram
      malathion/vial, respectively. The differences between these 2 colonies with
      respect to their tolerances to malathion may be a product of the age of each
      colony at the time assessments were made and/or the degree to which the parent
      stock used to start each colony was previously exposed to malathion in the field.

PMID- 10084147
TI  - Impact of naled on the mosquito vectors of eastern equine encephalitis virus.
AB  - This letter questions the appropriateness of methodology used in a study by
      Howard and Oliver (J. Am. Mosq. Control Assoc. 13:315-325; 1988). Two independent
      data sets, collected for different purposes by 2 different groups, were subjected
      to statistical analysis to determine if the data sets differed. The experimental
      "design," as described by the authors, is an example of pseudoreplication, which
      arises when replicates are collected at a scale finer than the one for which
      conclusions of statistical testing are intended to be drawn. All of the
      components of a properly designed field experiment (control, replication,
      randomization, and interspersion) are missing from this study. The authors
      proceed to draw a series of conclusions from the data presented. Few, if any, of
      the conclusions can be supported by the evidence presented. The assertions put
      forward in this paper could have a severe negative impact on efforts to prevent
      transmission of arboviruses or other pathogens to humans and domestic animals.

PMID- 10084148
TI  - Peroxin puzzles and folded freight: peroxisomal protein import in review.
AB  - Peroxisomes are organelles that perform a variety of functions, including the
      metabolism of hydrogen peroxide and the oxidation of fatty acids. Peroxisomes do
      not possess organellar DNA; all peroxisomal matrix proteins are post
      translationally translocated into the organelle. The mechanism of peroxisomal
      protein translocation has been the subject of vigorous research in the past
      decade. Many of the proteins (peroxins, abbreviated Pex) that play critical roles
      in peroxisome biogenesis have been identified through functional complementation
      of yeast strains and of Chinese hamster ovary cell lines that are defective in
      peroxisome biogenesis. Researchers are now turning towards biochemical and
      genetic analyses of these peroxins to define their roles in peroxisome biogenesis
      and to discover interacting protein partners. Evidence suggests that some of the
      interacting partners include molecular chaperones. Several current models for
      peroxisomal protein import are presented.

PMID- 10084149
TI  - Animal meal: production and determination in feedstuffs and the origin of bovine
      spongiform encephalopathy.
AB  - This contribution examines what animal meal is, how it is produced in rendering
      plants, and means of investigating feedstuff constituents. In addition to animal
      meal, numerous other products of animal origin are also on the market (e.g.,
      blood meal, bone meal, feather meal, gelatin). Constituents of animal origin can
      be detected in feedstuffs by microscopy, but determining the animal species from
      which the constituents are derived, as required by law in Germany, requires
      methods such as enzyme-linked immunosorbent assay and polymerase chain reaction.
      We consider the problem of trace contamination being introduced accidentally
      during the production of ruminants feedstuffs containing constituents of animal
      origin. The future of animal meal is discussed together with alternatives for
      disposing of animal carcasses and slaughtery offal, i.e., composting and
      incineration.

PMID- 10084150
TI  - Human neuroblastoma: from basic science to clinical debut of cellular oncogenes.
AB  - Neuroblastoma is a childhood embryonic tumor of migrating neuroectodermal cells
      derived from the neural crest and destined for the adrenal medulla and the
      sympathetic nervous system. It very often has a rapidly progressive clinical
      course, and although many advances have been made in understanding the
      development of this tumor, improving the survival rates particularly in patients
      with metastatic tumor has been a frustrating experience. The mechanisms leading
      to neuroblastoma are largely unclear, but nonrandom chromosomal changes
      discovered early suggested the involvement of genetic alterations. Most prominent
      among these is the amplification of the oncogene MYCN, which identifies a group
      of patients who have a particularly dire prognosis. Amplified MYCN is used today
      as a prognostic marker on which therapy design is based to a large extent. An
      unusual aspect of neuroblastoma is the high rate at which tumors regress
      spontaneously, even in infants with extensive liver involvement and numerous
      subcutaneous nodules. Identifying the molecular and cellular basis of spontaneous
      regression could result in improved therapeutic approaches. Neuroblastoma is a
      model tumor with many fascinating aspects but has remained a challenge to the
      pediatric oncologist.

PMID- 10084151
TI  - Attention modulates the blood oxygen level dependent response in the primary
      visual cortex measured with functional magnetic resonance imaging.

PMID- 10084152
TI  - Ultraviolet light-induced phase response curve for the locomotor activity rhythm
      of the field mouse Mus booduga.

PMID- 10084153
TI  - A molecular modeling study of B-DNA-intercalation complexes with amsacrine and
      related 9-anilino-acridines.
AB  - Computer molecular modeling studies of some complexes of amsacrine-derivatives
      with B-DNA-hexanucleotides were performed to shed new light on the DNA-binding
      mode of these drugs. The studies are based on routine methods, as are the
      semiempirical calculations, conformational analyses of the ligands, interaction
      field analyses, force field and molecular dynamics simulations of ligand/base
      paired DNA-complexes. The predictions suggest that the tested 9-anilino-acridines
      1, 3 and 4 bind by intercalation to the base-paired oligonucleotides. Depending
      on the substitution pattern of the tested 9-anilino-acridine-series compounds,
      some distinct binding modes and base sequence selectivities were observed.

PMID- 10084154
TI  - [Synthesis of substituted benzoylacrylic acids as potential antagonists of
      phospholipase A2].
AB  - Long chain alkylbenzenes were acylated with maleic anhydride and substituted
      maleic anhydrides. The resulting benzoyl acrylic acids were tested on
      phospholipase A2. The isomeric ratio (Z/E) of the benzoyl acrylic acids was
      estimated by NMR spectroscopy. A few acrylic acids cyclized to hydroxybutenolids.

PMID- 10084155
TI  - Synthesis of 3-aryl-1-[(4-phenyl-1-piperazinyl)butyl]indazole derivatives and
      their affinity to 5-HT1A serotonin and dopamine D1 receptors.
AB  - Eight 3-arylindazole derivatives have been synthesized and their affinity to 5
      HT1A serotonin and D1 dopamine receptors was investigated by radioligand
      analysis. Quantitative structure-activity relationships were studied using the
      Free-Wilson model. An increase in affinity to dopamine D1 receptors within
      substituents Br > Cl > CH3 at the 5-position of the 3-arylindazole molecule has
      been observed. Addition of a chlorine atom to the ortho-position the of phenyl
      ring let to even highest activity. Replacement of the hydrogen atom at the first
      position of the 3-arylindazole on the (phenylpiperazine)butyl substituent caused
      an increase of affinity and did not change the trends of affinity dependence on
      structure. An inverse dependence on the structure of the studied compounds was
      observed for the serotonin 5-HT1A receptors. Compounds containing a methyl group
      at the 5-position of molecule were more active than compounds containing
      halogens. A chlorine atom at the ortho-position of the phenyl ring decreased
      affinity. Replacement of the hydrogen atom at the first position of the molecule
      on the phenylpiperazine)butyl substituent led to an increase in affinity.
      Selectivity of the studied compounds varied within a wide range. Generally, the
      presence of the 3-aryl-indazole fragment in the new buspirone analogues increased
      their affinity to dopamine receptors and reduced their affinity to serotonin
      receptors. Compounds containing a bromine atom in the 3-arylindazole moiety may
      be promising ligands for D1 receptors.

PMID- 10084156
TI  - New renin inhibitors with hydrophilic C-terminus.
AB  - Four new peptide-based renin inhibitors, Boc-Phe(4-OMe)-MePhe-AHPPA-epsilon Ahx
      EA (11), Boc-Phe(4-OMe)-MeLeu-AHP-PA-epsilon Ahx-EA (15), Boc-Phe(4-OMe)-MePhe
      Sta-epsilon Ahx-EA (20) and Boc-Phe(4-OMe)-MeLeu-Sta-epsilon Ahx-EA (21) have
      been synthesized in search of structures with improved biological properties.
      They were designed as compounds with moderate hydrophobicity (5.28, 4.79, 4.79
      and 4.30), respectively. All synthesized inhibitors were resistant to
      chymotrypsin activity, all were poorly soluble in buffers pH 2.0 and pH 7.4. The
      inhibitory potency of renin activity in vitro of 11, 15, 20 and 21 expressed as
      IC50 was 7.0 x 10(-4), 7.5 x 10(-5), 6.0 x 10(-4) and 2.5 x 10(-4) M/l,
      respectively.

PMID- 10084157
TI  - Synthesis and biological screening of new 1,3-diphenylpyrazoles with different
      heterocyclic moieties at position-4.
AB  - 1,3-Diphenyl-1 H-pyrazole-4-carboxaldehyde (1) was reacted with barbituric acid,
      thiobarbituric acid, some activated nitriles and/or acetophenone to give the
      condensation products 2a, b, 3a-c and 4, respectively. The reaction of 1 with
      hydrazine hydrate, semicarbazide or thiosemicarbazide afforded the corresponding
      azomethines 5a-c. The compounds 3a, b, 4 and 5a, c were subjected for different
      sequence reactions to produce the title compounds. The antibacterial and
      antifungal activity of some selected derivatives were evaluated.

PMID- 10084158
TI  - Evaluation of the effect of polyethylene glycol 400 on the nasal absorption of
      nicardipine and verapamil in the rat.
AB  - This study has investigated the effect of polyethylene glycol (PEG) 400 on the
      intranasal absorption and ensuing pharmacokinetics of the calcium entry blockers
      nicardipine and verapamil in a rat model. To solutions of nicardipine in acetate
      buffer pH 5.0 and of verapamil in distilled water, PEG 400 was added in
      concentrations of 0-5%. The nasal bioavailability of nicardipine from plain
      buffered solution was 44%, and increased steadily to 56-79% in direct proportion
      to the amount of PEG 400 added. Verapamil, on the other hand, exhibited an
      intranasal bioavailability of 52% in the absence of PEG 400, and between 61-68%
      in the presence of increasing concentrations of PEG 400. None of the formulations
      tested was found to cause adverse effects on the morphology and integrity of the
      nasal mucosa.

PMID- 10084159
TI  - Formulation and in vitro/in vivo investigation of carbamazepine controlled
      release matrix tablets.
AB  - Carbamazepine controlled-release tablet formulations containing hydroxypropyl
      methylcellulose (HPMC) as matrix material at different concentrations were
      developed and evaluated in vitro and in vivo. The formulation containing 10% HPMC
      (HPMC-10) showed a controlled-release profile comparable to that of a
      commercially available, controlled-release carbamazepine preparation (Tegretol CR
      200). The kinetics of controlled-release carbamazepine tablets was examined in
      eight healthy volunteers. The peak plasma concentration of 1.99 +/- 0.56
      micrograms.ml-1 was obtained for HPMC-10 at 15.0 +/- 9.0 h, and 1.33 +/- 0.35
      micrograms.ml-1 for Tegretol CR 200 at 15.2 +/- 8.9 h, and AUC0-infinity values
      of 85.2 +/- 30.8 micrograms.h.ml-1 and 76.9 +/- 20.7 micrograms.h.ml-1,
      respectively. Developed formulation (HPMC-10) was found to be bioequivalent to
      Tegretol CR 200 and, controlled release was obtained with smoother concentration
      time curve resulting in less fluctuations.

PMID- 10084160
TI  - Effect of adhesive and drug reservoir on in vitro transdermal delivery of
      nicotine.

PMID- 10084161
TI  - Antiinflammatory activity of aqua(cresoxyacetato)-copper(II) complexes.

PMID- 10084162
TI  - Antifungal activity of 2'-substituted furanocoumarins and related compounds.

PMID- 10084163
TI  - Fluoride therapy in osteoporosis: the tide is ebbing.

PMID- 10084164
TI  - Interpreting findings from therapeutic trials in chronic joint diseases.

PMID- 10084165
TI  - Validity of the saliva ferning test for the diagnosis of dry mouth in Sjogren's
      syndrome.
AB  - OBJECTIVE: To study the validity of saliva ferning patterns as a diagnostic test
      for dry mouth in primary or secondary Sjogren's Syndrome (SS). METHODS: Salivary
      smears were collected from 25 patients with Sjogren's syndrome in the fasting and
      nonfasting state. All 25 patients had symptomatic xerostomia and xerophthalmia
      and a positive Shirmer's test. Smears were taken from four sites, the cheek,
      lower lip, tongue, and saliva. Tests were done for rheumatoid factor, antinuclear
      antibodies, and anti-Ro(SS-A) antibodies. The salivary smears were air-dried and
      examined under a light and a polarizing microscope. Smears from 25 healthy
      subjects were also examined as controls. RESULTS: Three patterns of salivary
      secretion were identified, namely normal geometric ferning, reindeer antler
      ferning, and thick branching ferning. All Sjogren's syndrome patients had
      abnormal salivary smears, usually with a combination of reindeer antler ferning,
      thick branching ferning, and mucosal squames. This combination was seen in six of
      the 25 fasting specimens (24%); most of the remaining fasting samples showed the
      reindeer antler ferning. Reindeer antler ferning alone was found in five fasting
      and four nonfasting samples: this pattern was absent from five fasting and five
      nonfasting samples in which mucosal squames were the only abnormal finding. All
      nonfasting control samples exhibited normal geometric ferning. Smears from the
      cheek and saliva provided the most illustrative findings. CONCLUSION: The saliva
      ferning test is a simple, reproducible, and useful diagnostic aid in autoimmune
      xerostomia, approximately equivalent to Shirmer's test in xerophthalmia.

PMID- 10084166
TI  - Efficacy of epidural steroids in low back pain and sciatica. A critical appraisal
      by a French Task Force of randomized trials. Critical Analysis Group of the
      French Society for Rheumatology.
AB  - OBJECTIVE: Several randomized trials have suggested recently that epidural
      steroid injections may not be a valid treatment in common low back pain and
      sciatica. To clarify this issue, we conducted a critical appraisal of relevant
      randomized trials published up to 1997. Attention was directed to methodological
      quality, results, and clinical implications. METHOD: A Medline search identified
      13 trials published between 1966 and 1997. Trial methodology was evaluated using
      a 100-point grid based on four groups of items, namely study population,
      therapeutic intervention, evaluation method, and data presentation and analysis.
      RESULTS: Methodology quality scores ranged from 12 to 84 and were unrelated to
      the results of epidural steroid therapy. Five trials demonstrated greater pain
      relief within the first month in the steroid group as compared to the control
      group. Eight trials found no measurable benefits. Obstacles to meaningful
      comparisons across studies included differences in the patient populations,
      steroid used, volume injected, and number of injections. None of the published
      studies used the injection modalities that are standard practice in France.
      CONCLUSION: Whether epidural steroids are effective in common low back pain and
      sciatica cannot be determined based on our review.

PMID- 10084167
TI  - Bone metastases from a paraganglioma. A review of five cases.
AB  - Paragangliomas are infrequent, usually benign tumors developed from neuroectoderm
      cells. The neck is the most common location, although some cases arise within the
      abdominal cavity, usually in the retroperitoneal space. We report five cases with
      bone metastases. In three patients, convincing evidence was obtained that the
      primary was in the retroperitoneal space. Clinical manifestations of metastatic
      bone disease occurred up to 17 years after the diagnosis of paraganglioma. Useful
      data were obtained from plain radiographs, magnetic resonance imaging, serum and
      urine catecholamine assays, and above all meta 123iodobenzylguanidine
      scintigraphy. Histologic and immunohistochemical studies of the lesion yielded
      the definite diagnosis. Surgery and radiation therapy are the two mainstays of
      therapy. Although rare, metastatic forms of paraganglioma should be borne in
      mind. This diagnosis should be entertained in patients with bone lesions and
      recent-onset arterial hypertension, irrespective of whether they report a history
      of surgery for a tumor, and even if this tumor was removed many years earlier and
      labeled benign.

PMID- 10084168
TI  - Peripheral primitive neuroectodermal tumors of bone. A review of three cases.
AB  - The recently individualized and still incompletely understood family of
      peripheral neuroectodermal tumors encompasses several tumor types, of which some
      have a predilection for bone. Immunocytochemical studies are essential and
      usually provide the diagnosis. A t(11;22)(q24;q12) translocation is present in
      over 80% of cases. Ewing's sarcoma is now viewed as an undifferentiated form of
      peripheral neuroectodermal tumor, and both tumors require management with
      combination chemotherapy plus radiation therapy and/or surgery. Contradictory
      data have been reported regarding the comparative prognosis of peripheral
      neuroectodermal tumor and Ewing's sarcoma, indicating a need for further studies
      in large numbers of patients. We illustrate these points by three case-reports,
      two in girls diagnosed with a vertebral primary at five and nine years of age,
      respectively, and one in a man diagnosed with a pelvic primary at 29 years of
      age.

PMID- 10084169
TI  - Mechanisms of pain in fibromyalgia.

PMID- 10084170
TI  - Systemic lupus erythematosus with optical neuromyelitis (Devic's syndrome). A
      case with a 35-year follow-up.
AB  - Optical neuromyelitis or Devic's syndrome is a very uncommon neurological
      manifestation of systemic lupus erythematosus. It is also associated with
      antiphospholipid antibodies, limited responsiveness to glucocorticoid treatment
      and a poor prognosis. We report the case of a female systemic lupus erythematosus
      patient who developed recurrent flares of optical neuritis and transverse
      myelitis. These flares consistently responded to glucocorticoid therapy. Despite
      the absence of overt anticardiolipin antibodies in the course of the disease,
      long-term anticoagulant therapy has been introduced with positive results.
      Treatments are usually of limited efficacy in Devic's syndrome. In our patient,
      however, aggressive glucocorticoid treatment resulted in prolonged survival.

PMID- 10084171
TI  - Refractory arthropathy after intravesical bacillus Calmette-Guerin therapy.
      Usefulness of isoniazide.
AB  - BACKGROUND: Arthritis associated with bacillus Calmette-Guerin immunotherapy
      usually responds dramatically to nonsteroidal antiinflammatory drug therapy.
      Isoniazid is generally reserved for other complications such as granulomatous
      hepatitis. CASE-REPORT: A 73-year-old man was admitted for fever, arthritis of
      the knees and right temporomandibular joint, an inflammatory swelling over the
      left Achilles tendon and bilateral conjunctivitis. The symptoms started in the
      wake of a course of intravesical bacillus Calmette-Guerin immunotherapy.
      Laboratory tests showed evidence of severe inflammation. Cultures of blood, urine
      and joint fluid specimens were negative, as were tests for autoantibodies and
      serologic tests for organisms known to cause reactive arthritis. Nonsteroidal
      antiinflammatory therapy was ineffective and glucocorticoid therapy produced only
      a partial response. All the symptoms resolved under isoniazid therapy in a dosage
      of 300 mg/day for three months. CONCLUSION: Use of antituberculous agents may be
      required in some cases of arthritis associated with bacillus Calmette-Guerin
      immunotherapy, most notably those with severe pyrexia.

PMID- 10084172
TI  - Neurological complications in insufficiency fractures of the sacrum. Three case
      reports.
AB  - Three cases of nerve root compromise in elderly women with insufficiency
      fractures of the sacrum are reported. Neurological compromise is generally felt
      to be exceedingly rare in this setting. A review of 493 cases of sacral
      insufficiency fractures reported in the literature suggested an incidence of
      about 2%. The true incidence is probably higher since many case-reports provided
      only scant information on symptoms; furthermore, sphincter dysfunction and lower
      limb paresthesia were the most common symptoms and can readily be overlooked or
      misinterpreted in elderly patients with multiple health problems. The
      neurological manifestations were delayed in some cases. A full recovery was the
      rule. The characteristics of the sacral fracture were not consistently related
      with the risk of neurological compromise. In most cases there was no displacement
      and in many the foramina were not involved. The pathophysiology of the
      neurological manifestations remains unclear. We suggest that patients with sacral
      insufficiency fractures should be carefully monitored for neurological
      manifestations.

PMID- 10084173
TI  - Polyarthritis following intravesical BCG immunotherapy. Report of a case and
      review of 26 cases in the literature.
AB  - OBJECTIVE: To delineate the characteristics of aseptic arthritis induced by
      intravesical BCG immunotherapy. METHODS: Review of a personal case and 26 cases
      from the literature. RESULTS: Mean number of intravesical BCG instillations at
      arthritis onset was five. Arthritis onset was within two weeks of the last
      instillation in 90% of cases. Half the patients had fever and half had
      conjunctivitis or uveitis. Symmetric polyarthritis was the most common pattern (n
      = 19), followed by oligoarthritis (n = 7). One patient had monoarthritis. The
      main targets were the knees (81%), ankles (48%), and wrists (40%). Twenty-six
      percent of patients reported back pain and 11% had sacroiliitis manifesting as
      pain or radiological changes. Mean erythrocyte sedimentation rate was 89 mm/h and
      mean C-reactive protein was greater than 70 mg/l. HLA B27 was positive in 56% of
      cases. Joint fluid usually exhibited inflammatory properties with
      polymorphonuclear neutrophils as the predominant cell type. Synovial membrane
      biopsy showed nonspecific synovitis in the six patients who had this
      investigation. Nonsteroidal antiinflammatory therapy was effective in 75% of
      cases. Three of the six patients given isoniazid and/or rifampin responded to
      this treatment. CONCLUSION: Although arthritis induced by intravesical BCG
      immunotherapy is more often polyarticular than oligoarticular, it shares many
      features with reactive arthritis.

PMID- 10084174
TI  - Jejunal telangiectasias as a cause of massive bleeding in a patient with
      scleroderma.
AB  - Telengiectasias (arteriovenous malformations) can be seen in scleroderma
      throughout the gastrointestinal tract, including the stomach, small bowel and
      colon. Massive gastrointestinal bleeding rarely results from these malformations
      in scleroderma. The case of a patient presenting with severe jejunal bleeding
      secondary to telangiectasias with special regard to the management is discussed.
      This case emphasizes the importance of endoscopic examination combined with
      mesenteric angiography in patients with scleroderma who present with a high index
      of suspicion of telangiectasias as a source of bleeding.

PMID- 10084175
TI  - Clinical features, autoantibody activity, and survival in nine Tunisian patients
      with IgD myeloma.

PMID- 10084176
TI  - Hydarthrosis of the ankle in a patient with a longitudinal stress fracture of the
      tibia.

PMID- 10084177
TI  - The publication rates of presentations at major Spine Specialty Society meetings
      (NASS, SRS, ISSLS).
AB  - STUDY DESIGN: A review of all the presentations at three major spine specialty
      meetings held over a 3-year period. OBJECTIVES: To determine the rate of
      publication in peer-reviewed journals after presentations at major spine meetings
      conducted annually by the following three organizations: North American Spine
      Society (NASS), Scoliosis Research Society (SRS), and International Society for
      the Study of the Lumbar Spine (ISSLS). SUMMARY OF BACKGROUND DATA: The rate of
      publication for presentations at national and international meetings has been
      determined for medical and surgical subspecialties. This rate has been used to
      judge the quality of the content of the meetings and to determine the validity of
      the research presentations. METHODS: All presentations either in poster or oral
      presentation form were entered into a database covering a 3-year period for spine
      specialty meetings conducted annually by the following three organizations: NASS
      1990 to 1992, SRS 1991 to 1993, and ISSLS 1991 to 1993. A computer search for
      each abstract was performed with the Melvyl Medline Plus database to determine if
      the abstract had been published in a peer-reviewed journal from 1990 to the end
      of 1997. Publication rates for presentations at these three meetings were
      determined over a 3-year period. RESULTS: A total of 1186 abstracts were listed
      over a 3-year period in the final programs of these three meetings for the years
      1991 to 1993 (SRS, ISSLS) and 1990 to 1992 (NASS). Of these 1186 abstracts, 516
      were published in peer-reviewed journals, giving an overall publication rate of
      43.5%. The publication rates for the three different meetings (NASS, SRS, ISSLS)
      were similar, with values of 40%, 47%, and 45% respectively. More than 90% of the
      publications resulting from these meetings were published within a period of 4
      years from the data of the meeting. CONCLUSIONS: The publication rates of
      presentations at three major spine specialty meetings are high and quite
      comparable with the publication rates of meetings in other medical
      subspecialties. This reflects the high quality of the meeting programs and
      validates their selection process.

PMID- 10084178
TI  - Volumetric change of the graft bone after intertransverse fusion.
AB  - STUDY DESIGN: Patients in whom good intertransverse fusion had been achieved were
      selected for the volumetric study of the fusion mass using sequential computed
      tomography scans. OBJECTIVES: To assess the natural volumetric change of
      intertransverse fusion mass and the effect of the disease entity and spinal
      instrumentation on the fusion mass volume. SUMMARY OF BACKGROUND DATA: The
      magnitude of volumetric change of the graft bone after intertransverse fusion is
      still inconclusive. METHODS: Fifteen adult patients who underwent decompression
      surgery with single-level lumbar and lumbosacral intertransverse fusion were
      selected for this study. Preoperative diagnoses were degenerative
      spondylolisthesis in nine patients and isthmic spondylolisthesis in six. Seven of
      the 15 patients received pedicle screw fixation. They were categorized into two
      major groups: 1) instrumented and noninstrumented groups and 2) isthmic and
      degenerative groups. To assess the volumetric change of the graft bone,
      sequential computed tomography scans were obtained 2 weeks after surgery and
      again 18 months after surgery. RESULTS: The overall initial mean graft volume was
      6251 mm3, which decreased to 2842 mm3 by 18 months after surgery (P < 0.001). The
      overall mean volume loss between the two periods was 54.8% of the initial graft
      volume. Although there was no significant difference in the mean graft volume
      between the groups at either 2 weeks or 18 months after surgery (P > 0.05 in all
      comparisons), the mean graft volume in each group decreased significantly during
      the observation period (P < 0.01 in all comparisons). There was no significant
      difference in the mean volume loss or in the ratio of residual volume to the
      initial graft volume between the groups during the study period (P > 0.05 in all
      comparisons). The initial graft volume correlated positively with the graft
      volume at 18 months after surgery (r = 0.612, P < 0.01) and volume loss (r =
      0.949, P < 0.01), but negatively with the residual volume ratio (r = -0.507, P <
      0.01). CONCLUSIONS: These results showed that more than one half of the initial
      graft bone volume was being absorbed during the consolidation processes of the
      graft bone, and that the volume loss during the period was not significantly
      affected by the spinal instrumentation or by the disease entity. It was also
      found that the greater the amount of the initial graft bone, the larger the
      fusion mass at 18 months after surgery. The volume loss, however, increased
      proportionally to an increase in the initial graft bone volume. The efficiency
      (ratio of residual volume to the initial graft volume) of the intertransverse
      fusion also tended to decline as the initial graft volume increased.

PMID- 10084179
TI  - Augmentation of spinal arthrodesis with autologous bone marrow in a rabbit
      posterolateral spine fusion model.
AB  - STUDY DESIGN: Posterolateral spinal fusion with autologous bone marrow aspirate
      in addition to autograft iliac crest bone graft in a rabbit model. OBJECTIVE: To
      demonstrate that the addition of autologous bone marrow can have positive effects
      on bone formation and spinal fusion. SUMMARY OF BACKGROUND DATA: Bone marrow has
      been shown to contain osteoprogenitor cells. A number of studies have
      demonstrated that bone formation is possible with autologous marrow injection
      into orthotopic sites such as that performed in femur fracture models. METHODS: A
      bone paucity model of posterolateral spine fusion was developed. The control
      animals received 0.8 g of morselized autogenous iliac crest bone graft harvested
      from a single iliac crest. The graft was mixed with 2 mL of clotted peripheral
      blood. In the experimental group, 2 mL of bone marrow aspirated from the opposite
      iliac crest was substituted for the peripheral blood clot. All rabbits were
      killed at 12 weeks, and the specimens were subjected to evaluation by
      posteroanterior radiography for the presence of fusion, computed tomography for
      bone volume, and biomechanical testing for stiffness. RESULTS: Successful fusion
      was achieved in 61% of the animals in the experimental group versus 25% in the
      control group (P < 0.05). The fusion mass in the experimental group had a mean
      volume of 919 +/- 387 mm3 versus 667 +/- 512 mm3 for the control group, as
      measured from computed tomography images. The results of the biomechanical
      testing validated the radiographic scoring system. The stiffness in specimens,
      graded as having a radiographic score of 4, was significantly greater than in
      specimens with radiographic scores of 1 and 2. CONCLUSION: In cases for which an
      adequate quantity of autogenous bone graft is not available, addition of bone
      marrow may facilitate greater bone formation and successful fusion.

PMID- 10084180
TI  - Traumatic instabilities of the cervical spine caused by high-speed axial
      compression in a human model. An in vitro biomechanical study.
AB  - STUDY DESIGN: Traumatic injury of the cervical spine was produced on human
      cadavers and evaluated with instability tests and radiographs. OBJECTIVE: To
      relate traumatic injuries of the cervical spine to instability and patterns of
      traumatic injury to different levels of impact energy. SUMMARY OF BACKGROUND
      DATA: Data from young human cadavers are rare in traumatic models of the cervical
      spine, and instabilities caused by axial compression with different impacts
      remain unknown. METHODS: Fourteen cervical spine specimens (C2-C4) obtained from
      fresh human cadavers were divided evenly into two groups and subjected to axial
      compressive impact with 30 J and 50 J impact energy, respectively. Pure moments
      in flexion-extension, left/right lateral bending, and left/right axial rotation
      were applied to each specimen before and after trauma. The maximum moment was 2.0
      Nm in each case. Ranges of motion and neutral zones were measured using
      stereophotogrammetry. RESULTS: Ranges of motion and neutral zones for both groups
      increased after trauma. No bony injury was observed on the radiographs after
      trauma with 30 J, but motions increased significantly in flexion, extension, and
      axial rotation. All specimens showed bony injuries after trauma with 50 J,
      whereas motions continued to increase significantly in all directions. The
      relative neutral zone values were larger than the corresponding range of motion
      values, except in flexion-extension after trauma with 50 J. CONCLUSIONS: The
      injury patterns of the cervical spine were associated with impact energy, and a
      high level of impact energy could produce either three-column injury or anterior
      middle-column injury. Instabilities of the cervical spine caused by compressive
      trauma increased with the level of impact energy. The neutral zone was more
      sensitive than the range of motion in representing spinal instability, whereas
      instability testing was more sensitive than radiographs in evaluating traumatic
      injury of cervical spine.

PMID- 10084181
TI  - Biomechanical analysis of anterior versus circumferential spinal reconstruction
      for various anatomic stages of tumor lesions.
AB  - STUDY DESIGN: Spinal reconstruction procedures for metastasis evaluated
      biomechanically using human cadaver specimens. OBJECTIVE: To investigate the
      stiffness of anterior versus circumferential spinal reconstructions for different
      anatomic stages of tumor lesions. SUMMARY OF BACKGROUND DATA: Metastatic tumors
      predominantly involve the vertebral bodies. Although anterior instrumentation and
      strut grafts provide excellent stability, it remains unclear to what extent
      vertebral destruction requires anterior reconstructions alone versus combined
      anterior and posterior procedures. METHODS: Ten human cadaveric thoracolumbar
      spines were used. The L1 vertebral body and posterior elements were resected
      sequentially based on Weinstein's anatomic zone classification for tumor lesions.
      Anterior reconstruction was performed between T12 and L2 using an iliac strut
      graft and the Kaneda SR system (AcroMed, Cleveland, OH). For circumferential
      reconstruction, the Cotrel-Dubousset hook and rod system was combined with the
      anterior reconstruction procedure. Experimental groups included the intact
      condition and five reconstruction stages: anterior reconstructions for
      corpectomy, subtotal and total spondylectomies, and circumferential
      reconstructions for subtotal and total spondylectomies. Nondestructive
      biomechanical testing was performed under four different loading modes. RESULTS:
      All the reconstruction groups except anterior instrumentation alone for total
      spondylectomy returned stiffness to a level equivalent or higher to that of the
      intact spine. There were no statistical differences observed between anterior and
      circumferential reconstruction for subtotal spondylectomy. Anterior
      instrumentation alone for total spondylectomy did not restore stiffness to the
      intact level, and demonstrated significantly lower stiffness than that of
      circumferential reconstruction. CONCLUSIONS: For corpectomy or subtotal
      spondylectomy, anterior reconstruction alone can provide stiffness equivalent to
      circumferential reconstruction. However, total spondylectomy significantly
      reduces the anterior reconstruction stiffness, suggesting the need for combined
      anterior and posterior procedures.

PMID- 10084182
TI  - Anatomic relation between the cervical pedicle and the adjacent neural
      structures.
AB  - STUDY DESIGN: An evaluation of the anatomic relation between the cervical
      pedicles and the adjacent neural structures. OBJECTIVES: To determine
      quantitatively the antomic relation of the cervical pedicles to the adjacent
      nerve roots and dural sac. SUMMARY OF BACKGROUND DATA: Transpedicular screw
      fixation in the cervical spine has been reported, but little quantitative data
      regarding the anatomic relation between the cervical pedicles and the surrounding
      neural structures are known. METHODS: Twenty cadavers were used for dissection to
      observe the relations of the cervical pedicles to the adjacent dural sac and
      nerve roots. After removal of whole posterior bony elements including the spinous
      processes, laminas, and lateral masses, the isthmus of the pedicles, the dural
      sac, and the nerve roots of C3-C7 were exposed. Direct measurements included the
      distance from the pedicle to the superior and inferior nerve roots and the dura.
      Also, the pedicle height and width were measured at its isthmus. RESULTS: No
      distance was found between the pedicle and the superior nerve root, nor between
      the pedicle and the dural sac at C3-C7 for all specimens. The mean distances
      between the pedicle and the inferior nerve roots for all specimens ranged from
      1.4 to 1.6 mm. The mean pedicle heights and widths for all specimens at C3-C7
      ranged from 6.0 to 6.5 mm and 4.7 to 5.3 mm, respectively. A significant
      difference between male and female specimens was noted in the pedicle heights for
      all levels measured (P = 0.001), and in the pedicle widths for the levels of C4
      and C6 (P = 0.05). CONCLUSIONS: This study suggests that the incidence of
      neurologic injuries may be higher in screw penetration of the medial or superior
      cortex of the pedicle than in screw penetration of the inferior cortex of the
      pedicle.

PMID- 10084183
TI  - Can intramedullary signal change on magnetic resonance imaging predict surgical
      outcome in cervical spondylotic myelopathy?
AB  - STUDY DESIGN: A retrospective study evaluating magnetic resonance imaging,
      computed tomographic myelography, and clinical parameters in patients with
      cervical spondylotic myelopathy. OBJECTIVES: To investigate whether magnetic
      resonance imaging can predict the surgical outcome in patients with cervical
      spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: No previous studies have
      established whether areas of high signal intensity in T2-weighted magnetic
      resonance images can be a predictor of surgical outcomes. METHODS: Fifty patients
      with cervical spondylotic myelopathy were examined by magnetic resonance imaging
      and computed tomographic myelography before surgery and by delayed computed
      tomographic myelography after surgery. The correlation between the recovery rate
      and the clinical and imaging parameters was analyzed. RESULTS: The best
      prognostic factor was the transverse area of the spinal cord at maximum
      compression (correlation coefficient, R = 0.58). The presence of high signal
      intensity areas on T2-weighted magnetic resonance images correlated poorly with
      the recovery rate (R = -0.29). However, patients with multisegmental areas of
      high signal intensity on T2-weighted magnetic resonance images tended to have
      poor surgical results associated with muscle atrophy in the upper extremities.
      Postoperative delayed computed tomographic myelography showed that multisegmental
      areas of high signal intensity on T2-weighted magnetic resonance images probably
      represent cavitation in the central spinal cord. CONCLUSIONS: Patients with
      multisegmental areas of high signal intensity on T2-weighted magnetic resonance
      images tended to have poorer surgical results. However, the transverse area of
      the spinal cord at the level of maximum compression was a better prognostic
      indicator.

PMID- 10084184
TI  - Pachymeningeal gadolinium enhancement of the lumbar region secondary to neuraxis
      hypotension.
AB  - STUDY DESIGN: A case of diffuse pachymeningeal gadolinium enhancement of the
      lumbar region secondary to neuraxis hypotension is presented. OBJECTIVE: To
      report a case of diffuse pachymeningeal gadolinium enhancement of the lumbar
      region and to show the importance of considering neuraxis hypotension in the
      differential diagnosis of this type of enhancement so as to avoid excessive
      invasive and noninvasive diagnostic testing. SUMMARY OF BACKGROUND DATA: Diffuse
      pachymeningeal gadolinium enhancement of the lumbar region secondary to neuraxis
      hypotension has not been reported previously. METHODS: A case of diffuse
      pachymeningeal gadolinium enhancement of the lumbar region is presented in the
      context of clinical signs and symptoms replete with a history of cerebrospinal
      fluid diversion that strongly suggest neuraxis hypotension. RESULTS: The
      patient's clinical presentation and history of shunting implicated neuraxis
      hypotension as a cause of the diffuse dural enhancement. CONCLUSION: Proper
      attribution of the dural gadolinium enhancement to neuraxis hypotension helped
      avoid a dural biopsy with its potential attendant morbidity. It is important to
      consider neuraxis hypotension in the differential diagnosis of diffuse
      pachymeningeal enhancement occurring anywhere in the central neuraxis to avoid
      unnecessary diagnostic testing with its attendant morbidity and cost.

PMID- 10084185
TI  - A controlled prospective outcome study of implantable electrical stimulation with
      spinal instrumentation in a high-risk spinal fusion population.
AB  - STUDY DESIGN: A series of 65 instrumented patients without stimulation were
      compared with a later series of 65 patients with instrumentation and implantable
      electrical stimulation. The groups were evaluated for risk factors, age,
      diagnostic groups, levels fused, and radiographic and clinical success.
      OBJECTIVES: To test the efficacy of electrical stimulation in instrumented high
      risk lumbar fusions. SUMMARY OF BACKGROUND DATA: Spinal instrumentation and
      implantable electrical stimulation have been shown to improve fusion success
      rates. METHODS: All patients were instrumented via pedicle screws and autologous
      bone graft. Diagnostic groups were evaluated, and the risk factors in each group
      were identified and compared. Postoperation management and follow-up regimen were
      similar in each group. Radiographs were evaluated via Dawson's criteria and
      confirmed by an independent radiologist. Clinical success was evaluated via the
      Modified Smiley-Webster Scale and confirmed by a second orthopedic surgeon.
      RESULTS: Fusion success was 95.6% in the stimulated group compared with 87% in
      the nonstimulated group (P = 0.05). Clinical success was 91% in the stimulated
      group and 79% in the nonstimulated group (P = 0.02). In a workers' compensation
      subset, fusion success was 93% in the stimulated group and 81% in the
      nonstimulated group. Clinical success was 57% in the stimulated group and 46% in
      the nonstimulated group. CONCLUSIONS: The results from using both instrumentation
      and electrical stimulation in a high-risk pool of patients show a statistically
      significant difference, with higher rates of fusion and clinical success than in
      a similar pool that did not receive stimulation.

PMID- 10084186
TI  - Intraoperative radiation therapy for metastatic spinal tumors.
AB  - STUDY DESIGN: Retrospective examination of 37 patients with metastatic spinal
      tumors treated with intraoperative radiation therapy. OBJECTIVE: To propose a new
      technique for local control of metastatic spinal tumors. SUMMARY OF BACKGROUND
      DATA: No reports of intraoperative radiation therapy for metastatic spinal tumors
      have been published as of the time of this writing. METHODS: Between December
      1992 and April 1996, intraoperative radiation therapy was performed in 37
      patients with spinal metastasis. In all but one patient, the spinal cord was
      protected during intraoperative radiation therapy by a lead shield to prevent
      radiation myelopathy. In addition to intraoperative radiation therapy, 22 of the
      37 patients received external radiation therapy, either before or after their
      operation. Although the authors had recommended a dose of approximately 30 Gy of
      external radiation therapy after wound suture removal to patients who did not
      receive preoperative radiation therapy, the remaining 15 patients did not receive
      external radiation therapy, either by choice or because they received alternative
      therapy. Adjuvant chemotherapy for various cancers was administered to 9 of the
      37 patients, including 4 of the aforementioned 15. RESULTS: All patients attained
      clinical improvement in pain, neurologic function status, or both, with no
      evidence of local recurrence. Radiation myelopathy developed in the one patient
      whose spinal cord was not protected during intraoperative radiation therapy.
      Eleven patients experienced metastasis in vertebrae that were not surgically
      treated. CONCLUSION: Intraoperative radiation therapy appears to achieve good
      palliation and may be useful for local control of spinal metastases.

PMID- 10084187
TI  - Radiographic verification of pedicle screw pilot hole placement using Kirshner
      wires versus beaded wires.
AB  - STUDY DESIGN: Kappa statistics were used to compare the accuracy of two different
      techniques for verifying pedicle screw pilot hole placement in cadaveric
      vertebrae. OBJECTIVE: To determine whether clinicians radiographically detect
      misplaced pedicle screw holes with greater sensitivity and specificity when
      beaded wires rather than straight Kirschner wires are used. SUMMARY OF BACKGROUND
      DATA: Pedicle screws commonly are used in orthopedic surgery to obtain and
      maintain spinal stability. Pedicle screws are reportedly misplaced at a rate of
      20% to 40%. Radiographic verification is commonly used to place pedicle screw
      pilot holes, but this technique is known to be less than 100% accurate. Computer
      assisted techniques may allow more accurate screw placement, but these techniques
      require expensive equipment. METHODS: Pedicle screw pilot holes were drilled into
      12 human lumbar and thoracic vertebrae. Some of the holes were misplaced
      deliberately so that they violated the pedicle walls. Lateral and posteroanterior
      radiographs of the vertebrae were evaluated by 13 experienced orthopedic spine
      surgeons and 3 inexperienced observers. At different times, the observers were
      shown radiographs depicting Kirschner wires or beaded wires placed in the pilot
      holes. Observers indicated whether they thought the pedicle screw pilot hole
      violated the pedicle. RESULTS: The sensitivity and specificity of using
      posteroanterior or lateral radiographs to detect misplaced pedicle screws were
      increased when beaded wires were placed in the pilot holes. CONCLUSIONS:
      Radiographic evaluation of beaded wires placed in pedicle screw pilot holes can
      be both sensitive and specific for misplaced screws. The highest sensitivity and
      specificity were found using posteroanterior radiographs.

PMID- 10084188
TI  - Temporary external transpedicular fixation of the lumbosacral spine.
AB  - STUDY DESIGN: In this study, 133 patients with incapacitating low back pain
      underwent temporary external transpedicular fixation of the lumbosacral spine in
      a prospective trial. Of these patients, 67% had undergone one or more spinal
      procedures in the past. On the basis of temporary external transpedicular
      fixation, 55 of 133 patients were treated conservatively. With an average follow
      up period of 37 months, the clinical results were analyzed. OBJECTIVE: To
      evaluate temporary external transpedicular fixation as a test for selecting
      suitable candidates for fusion of the lumbosacral spine. SUMMARY OF BACKGROUND
      DATA: The few reports regarding this test are contradictory in terms of
      predictive value and morbidity. Only three reports include a placebo trial.
      METHODS: All patients were tested with the external fixator in three different
      positions: neutral fixation, slight distraction, and nonfixation (bars
      disconnected). The patient was unaware of the exact position of the external
      fixator and thus served as his or her own control. Before and during the test and
      at follow-up examination, pain was assessed on a visual analog scale. RESULTS: In
      the group that eventually underwent spinal fusion, the average preoperation
      visual analog scale score was 77. During test fixation, the average score was 26,
      in nonfixation 69, and at follow-up after surgery 40. In the control group, these
      figures were 75, 53, 44, and 71, respectively. As statistical analysis showed,
      the only factors that could be associated with the improved pain score was the
      performance of the spinal fusion (P = 0.0001) and the duration of low back pain
      before the test (P = 0.04). CONCLUSION: In selecting suitable candidates for
      spinal fusion, temporary external transpedicular fixation (including a placebo
      trial) can be a valuable test.

PMID- 10084189
TI  - Spinal cord compression caused by unusual location and extension of ossified
      ligamenta flava in a Caucasian male. A case report and literature review.
AB  - STUDY DESIGN: A case report of a spinal cord compression caused by ossification
      of the ligamenta flava is presented together with a review of the literature.
      OBJECTIVE: To present the diagnosis of ossification of the ligamenta flava in a
      Caucasian man with a proximal thoracic myelopathy. SUMMARY OF BACKGROUND DATA:
      This case shows that the upper parts of the thoracic spine can be involved in
      ossification of the ligamenta flava, which never before has been reported in
      Caucasian individuals. Furthermore, it is advised that computed tomography
      scanning and magnetic resonance imaging be combined to provide an accurate
      diagnosis and proper preoperative evaluation of the bony changes, spinal cord,
      and compression of the spinal cord. METHODS: A patient with a thoracic spinal
      cord compression caused by ossification of the ligamenta flava was treated
      surgically and made a good clinical recovery. Imaging studies, surgical findings,
      and results of histopathologic investigations were analyzed to substantiate the
      diagnosis. RESULTS: The results of the surgical findings seemed to be in contrast
      with those of the imaging studies. This contrast was occasioned by the uncommon
      perioperative finding of a fusion of the completely ossified upper and lower
      parts of the involved adjacent ligamenta flava. Ossification of the ligamenta
      flava was diagnosed by histopathologic examination, which revealed endochondral
      ossification and lamellar bone formation without fragments of ligamenta flava.
      CONCLUSION: Although rarely reported in whites, ossification of the ligamenta
      flava should be considered in all patients presenting with a spinal cord
      compression, even at high thoracic levels. The prognosis after decompressive
      surgery can be good, especially if intramedullary hyperintensities are absent on
      preoperatively performed T2-weighted magnetic resonance images.

PMID- 10084190
TI  - Severe progressive osteoporotic spine deformity with cardiopulmonary impairment
      in a young patient. A case report.
AB  - STUDY DESIGN: This report describes a young patient with a rapidly progressive
      kyphosis caused by collapse of a severely osteoporotic thoracolumbar spine, which
      led to impairment of cardiopulmonary function. OBJECTIVES: To highlight the
      treatment strategy, difficulty of diagnosis, operative stabilization, and
      outcome. SUMMARY OF BACKGROUND DATA: Little is known about natural history,
      treatment options, and results of this condition. METHODS: The magnitude of bone
      loss was measured by dual-energy x-ray absorptiometry, and the deformity was
      visualized by computed tomography and magnetic resonance imaging. Laboratory
      investigations also were performed before and during halotraction in an attempt
      to establish a diagnosis. These data constituted the preoperation information
      required to assess later results of medical and surgical intervention. RESULTS:
      An extensive evaluation of possible underlying etiologies failed to identify a
      specific etiology. Before and during halotraction, bone mineral substitutes were
      given, partially correcting the bone mineral content as measured on repeated dual
      energy x-ray absorptiometry scans. In addition, the thoracic kyphosis was
      partially corrected, from 100 degrees to 70 degrees Cobb's angle. Subsequently, a
      combined anterior and posterior stabilization was performed from C7 to S1 using a
      vascularized fibula graft, a double Isola rod system (AcroMed, Cleveland, OH),
      and a carbonate apatite cancellous bone cement to reinforce the pedicle screws.
      At follow-up assessment 40 months surgery, the patient was asymptomatic and fully
      mobilized, with radiographs showing complete incorporation of the grafts and no
      loosening of the fixation device. CONCLUSIONS: The diagnostic and therapeutic
      difficulties of progressive spine deformity caused by severe osteoporosis in
      young patients emphasizes the importance of a thoroughly planned treatment
      strategy. Halotraction is recommended to stop progression of the deformity, or
      even partially correct it, and to allow time to search for the diagnosis and bone
      mineral substitution. Surgical treatment using vascularized fibular strut grafts
      and a strong fixation device was successful. Biocompatible carbonated apatite
      cancellous bone cement was successfully used to reinforce pedicle screw fixation.

PMID- 10084191
TI  - Principles of medical decision making.
AB  - The consequences of medical decisions are inherently uncertain at the decisive
      moment. Using clinical examples related to the diagnosis and management of low
      back pain, the authors review some principles that can help physicians deal with
      this uncertainty. This article addresses the following: the use of probability as
      a useful representation of uncertainty, the use of Bayes' theorem to update
      probability estimates when new information is obtained, the measurement of a
      diagnostic test's accuracy, the use of the threshold model for choosing a
      diagnostic test, the principles of expected-value decision making, the use of
      utility assessment as a way of attaching value to outcomes, and the use of
      quality-adjusted life years as a measure of value. These principles can aid
      physicians in approaching complex and uncertain decisions with their patients. As
      the use of computers becomes more integrated into the process of care, the
      opportunity exists to move formal decision models from the policy level to the
      patient care level.

PMID- 10084192
TI  - Preliminary design and experimental studies of a novel soft implant for
      correcting sagittal plane instability in the lumbar spine.

PMID- 10084193
TI  - The study of apoptosis in spine pathology.

PMID- 10084194
TI  - Analysis of aging and degeneration of the human intervertebral disc.

PMID- 10084195
TI  - Comparison of surgical specimens with normal controls.

PMID- 10084196
TI  - 28th Annual meeting of the German Society for Thoracic and Cardiovascular
      Surgery. Dresden, February 24-27, 1999. Abstracts.

PMID- 10084197
TI  - [Health council report: "Antimicrobial growth promoters"].
AB  - The Health Council of the Netherlands has issued a report on the risk of
      development of resistance among bacteria as result of the use of antibiotics as
      growth promotors in livestock farming. The committee appointed by the Health
      Council conclude that the use of antimicrobial growth promotors contributes to
      the problem of resistance among human pathogens. The conclusions are based on
      evidence regarding the development of resistance in livestock as the result of
      the use of antimicrobial growth promotors, the possibility of
      colonisation/infection of humans with resistant bacteria from the intestinal
      flora of productive livestock, and the transfer of resistance genes from
      livestock bacteria to human pathogenic microorganisms. Effective measures for the
      limitation of the public health risk should focus on termination of the use of
      antimicrobial growth promotors that confer resistance to (related) antibiotics
      currently used (or which will be available) to treat patients suffering from
      bacterial infections. In addition, the committee advised ending the use of
      antimicrobial growth promotors in 3 years.

PMID- 10084198
TI  - [Characteristics of pedigree cat breeding in the Netherlands: breeds, population
      increase and litter size].
AB  - A survey of the Dutch Cat Fancy was carried out to determine reproductive,
      patterns of pedigree cats. The data of the present study were obtained by
      questioning the pedigree registers of the cat clubs participating in the
      foundation 'Overleg Platform van de Nederlandse Cat Fancy'. The Dutch Cat Fancy
      registers 34 different cat breeds. From 1992 up to 1996 a total of 25.985 litters
      were registered. Over this period the number of litters increased from 4989 to
      5313. Litters from Longhair and Exotic Shorthair cats comprised the biggest group
      and accounted for 55% of the total number of litters. However, over this period,
      the number of Longhair and Exotic Shorthair litters decreased by 9%. Litters from
      British Shorthair, Birman, Maine Coon and Norwegian Forrest Cat increased in
      number as did litters from small breeds such as Ragdoll, Bengal and Sphynx.
      Litters from Abyssinian, Siamese, Oriental Shorthair cats remained relatively the
      same. The average litter size of the total cat population, based on pedigree
      certificates, was calculated at 3.3 kittens per litter. For different breeds
      litter size varied from 2.7 (Longhair and Exotic Shorthair) to 4.3 (Burmese and
      Maine Coon). Taking into account an average age of 14 years, the total Dutch
      pedigree cat population was estimated at 240,000 viz. about 10% of the total cat
      population.

PMID- 10084199
TI  - [Benjamin Rush (1746-1813)].

PMID- 10084200
TI  - [Interview with Johan Hoevers. Veterinarian to psychologist. Interview by Sophie
      Deleu].

PMID- 10084201
TI  - [The non-vaccination policy].

PMID- 10084202
TI  - Tetrahymena pyriformis in the ciliate mobility test. Validation and description
      of a testing procedure for the registration of harmful substances in the air as
      well as the effects of cigarette smoke on the human respiratory ciliated
      epithelium.
AB  - The damage of the human respiratory ciliated epithelium or its ciliar activity
      caused by mixtures of harmful substances in the air and cigarette smoke is a
      considerable parameter for the judgment of acute harmful influences on the human
      respiratory tract. As an immediate measuring or a quantitative statement about
      the influence on cilia in vivo at human beings is extremely difficult and
      problematic, a convenient model experimental system in form of the so called
      ciliate mobility test (CMT) has been used. In this connection the influence on
      cilia of the protozan single-celled organism Tetrahymena pyriformis, regarding
      its average speed of locomotion has been taken as standard. The proof, that the
      cilia are identical in morphological and functional respect at the human ciliated
      epithelium and at T. pyriformis has been reached by electron optical comparative
      representation and bibliographical known substances, influencing cilia
      (theophylline, bromhexine, ambroxol, terpin hydrate, mercaptoethanesulfonat
      sodium, amrinon, salbutamol, tetracosactid-hexaacetate, histamine, and phenol).
      With regard to the comparability and applicability to the human respiratory
      ciliated epithelium we have been able to gain statements by means of the CMT. By
      constructing a special reaction vessel the influence of harmful gases at a thin
      layer of ciliate culture suspension (1 cm) for a standardised exposure time (1
      hour) has been made possible and with that a model for the comparability with the
      conditions of the human respiratory ciliated epithelium has been created. A
      number of harmful gases, that are relevant in the air hygiene (CO, CO2, N2, N2O,
      NO2, O3, SO2) as well as cigarette smoke at active smokers (primary stream smoke)
      and the inhalation of the smoke of other people's cigarettes has been tested. It
      turned out, that especially NO2 (nitric oxide) shows a high ciliar toxicity,
      while the controversially discussed ozone (O3) has not resulted in detraction of
      cilia. CO, N2O and SO2 have been--to a great extent--harmless on cilia in the
      concentration range relevant in the air hygiene. Remarkable are the results, that
      cigarette smoke shows clear toxic effects on cilia both at active smoking, as
      well as the inhalation of the smoke of other people's cigarettes. With that
      another contribution to the discussion about the harmfulness of active smoking
      and the inhalation of the smoke of other people's cigarettes is made.

PMID- 10084203
TI  - [Genotoxicity of stack gas condensates of Bavarian waste incineration plants. I.
      Stack gas condensate--sample collection techniques].
AB  - Investigations into the toxicity and the chemical analytics of stack gas
      condensates from 21 waste incineration plants (locations in Bavaria) were
      undertaken in the years 1990 to 1995. A decisive prerequisite was the development
      of a simple, standardizable technique for sample collection. It was done by
      condensating stack gases at 0 to 5 degrees C in an intensive glass condensator.
      Certain types of compounds showed a different behaviour of separation at the
      temperatures which were used. Whereas bivalent ionic mercury and chlorophenols
      were comparatively well separated with amounts of 60 to 95% and the
      polychlorinated dioxins, furans and biphenyls (PCBs) were sufficiently separated
      with 20 to 60%, less than 10% of the chlorobenzenes and polycyclic aromatics
      (PAHs) were found in the condensates. Sufficiently sensitive biological test
      procedures must be chosen for a biomonitoring of the condensates on geno- and
      immunotoxic effects to keep the required quantity of the condensates within
      practicable limits. The concentration of organic wastes was done through a solid
      phase extraction for the genotoxicity testing in the period from 1990 to 1991,
      and uniformly through a dichloromethane extraction for the biological and the
      simultaneous chemical analytical investigations from 1992 to 1995.

PMID- 10084204
TI  - [Genotoxicity of stack gas condensates of Bavarian waste incineration plants. II.
      Suitability of fast bacterial tests of emission monitoring].
AB  - The genotoxicity of stack gas condensates of 21 waste incineration plants
      (located in Bavaria) was examined in the years 1990-1995 using two bacterial
      short time tests. The SOS chromotest was carried out with the tester strains
      Escherichia coli PQ37, PQ243 and PQ300. In addition, for the purpose of
      comparison, the Ames-Test was performed for selected examples with the tester
      strains Salmonella typhimurium TA97, TA98, TA100 and TA1537. In a pilot study,
      carried out in the years 1990 to 1991, the stack gas condensates from five plants
      were examined. They showed clear genotoxic and mutagenic effects. On the other
      hand, in subsequent tests we generally discovered only weak inductions for 9 of
      18 crude and 24 of 78 clean gas condensate extracts, mostly after metabolic
      activation. Four plants were tested continuously in the years 1992 to 1995. Three
      of them showed a clear reduction of the detectable genotoxic potential. The
      fourth one gave negligible SOS inducing emissions in the whole examining period.
      On the other hand, for 6 of the 21 tested plants we found chromotest positive
      results even at the last test point. Correlations between the SOS inducing
      potential of the stack gas condensates and the analytical parameters detected at
      the same time (6 summary parameters, 24 inorganic and 63 organic chemical
      parameters) were not evident. Only the two highest emissions of nitropyrenes were
      associated with SOS inductions. Organic substances which are not analytically
      detected or synergistic effects might be responsible for the SOS inducing potency
      of the other genotoxic stack gas condensates.

PMID- 10084205
TI  - [Genotoxicity of stack gas condensates of Bavarian waste incineration plants.
      III. Emission monitoring with a simple UDS assay using the human lung cell lines
      NCI-H 322 and 358].
AB  - For the validation of the genotoxicity testing on stack gas condensates from
      waste incineration plants using bacterial short time tests (15), a modified UDS
      assay with the lung cell lines NCI-H 322 and 358 was developed. The UDS assay is
      more sensitive than the SOS chromotest and discriminates better between the
      negative or weakly positive and the clearly positive samples. It has a high
      sensitive and specificity and also accuracy, is practicable in a comparatively
      simple, speedy and reasonably priced manner and is therefore appropriate for an
      emission monitoring similar to simple bacterial short time tests. Especially in
      strongly concentrated crude and clean gas condensates, maximal induction factors
      were seen in the range of strong UDS inducers. From 55 samples on 16 incineration
      plants tested in the years 1992 to 1995, in 48 we found weak to strong UDS
      inductions in at least one of the two test cell lines. From three plants examined
      continuously in this period only two emitted stack gases with constantly low
      genotoxicity at the end of sampling. 5 clean gas condensates, that were taken in
      random samples from 3 other plants in the period 1994 to 1995, proved to be non
      genotoxic in the UDS assay. However, one of these plants emitted stack gases with
      high cytotoxicity, which might have masked UDS-inducing single substances. It is
      not possible to make a statement on the human toxicological relevance. However, a
      clearly positive development towards more harmless stack gas condensates was
      established. A definite correlation could not be shown between the chemical
      analysis of the detected cancerogenic organic single substances of the samples
      and the detected UDS inductions. Further investigations for finding strong UDS
      inducers from the substance spectrum of municipal stack gas emissions are
      necessary.

PMID- 10084206
TI  - [Genotoxicity of stack gas condensates of Bavarian waste incineration plants. IV.
      Overview and short comments on the results].
AB  - Emissions from waste incineration plants can be monitored relatively simply and
      cost-effectively via stack gas condensates. We compared quantitative chemical
      analytic data of stack gases with two genotoxicity tests. The tests employed,
      i.e. a new, simple UDS assay variant with the human lung cell lines NCI-H 322 and
      358, developed for this purpose, and an automated version of the SOS chromotest,
      were validated with respect to the contents of stack gases analytically detected.
      As judged by Bavarian waste incineration plants, sampled in the years 1990 to
      1995, we obtained the following principle results: A drastic reduction of the
      genotoxicity from stack gases in the sampling period was observed with both
      tests. There were found genotoxic stack gases with the more sensitive UDS assay
      also in modern plants at the end of sampling period. Up to 99% of the organic
      components were not detected by chemical analysis despite an extensive program of
      analytics. The concentration of the quantified cancerogenic organic single
      substances from the samples did not suffice to explain genotoxic effects in the
      stack gases. Unknown, not identified stack gas contents are mainly responsible
      for the genotoxic potential of the stack gases. According to our results,
      emissions of modern waste incineration plants are likely to increase the
      genotoxic hazardous potential of the air only insignificantly even in pollution
      free zones.

PMID- 10084207
TI  - Microbiological efficacy of superheated steam. I. Communication: results with
      spores of Bacillus subtilis and Bacillus stearothermophilus and with spore earth.
AB  - For the spores of Bacillus subtilis and Bacillus stearothermophilus as well as
      for spore earth (acc. DIN 58,946 Part 4 of August 1982), the dependence of
      resistance on the superheating of the steam used to kill germs was determined. A
      material (glass fibre fleece) was used as the germ carrier which does not
      superheat on contact with steam. The temperature of the saturated steam was 100
      degrees C (B. subtilis) and 120 degrees C (B. stearothermophilus and spore
      earth). The yardstick for the resistance of the spores or bioindicators was the
      exposure period of the saturated or superheated steam at which 50% of the treated
      test objects no longer showed any viable test germs. The spores of Bacillus
      subtilis were far more sensitive to superheating of steam and reacted far more
      than the spores of Bacillus stearothermophilus and the germs in the spore earth.
      When superheating by 4 Kelvin the spores of Bacillus subtilis were approximately
      2.5 times more resistant than they were to saturated steam. The resistance of
      Bacillus stearothermophilus and spore earth was only slightly higher up to
      superheating by 10 Kelvin. The spores of Bacillus subtilis had the highest
      resistance during superheating by 29 Kelvin; they were 119 times more resistant
      than they were to saturated steam. The resistance maximum of the spores of
      Bacillus stearothermophilus was at an superheating by around 22 Kelvin. However,
      the spores were only 4.1 times more resistant than they were to saturated steam.
      When using steam to kill germs, we must expect superheated steam. This raises the
      question whether the spores of Bacillus stearothermophilus, with their weaker
      reaction to the superheating of steam, are suitable as test germs for
      sterilisation with steam in all cases.

PMID- 10084208
TI  - [The efficacy of repeated disinfection of disposable gloves during usage].
AB  - The efficacy of disinfecting medical gloves with isopropanol 60% (v/v) while they
      are worn was assessed for 4 different brands of latex gloves (Biogel Diagnistic
      (A), Safeskin Satin Plus (B), Safeskin LPE (C) and Baxter Non-Sterile Latex Exam
      Gloves (D)) and one latex-free nitrile glove (100% Nitrile N-Dex (E)). Even in
      the presence of coagulated blood disinfection of the gloves was more efficient
      than disinfection of the bare hand. The efficacy of the disinfection of glove C,
      D and E decreased if 10 disinfections were carried out successively. An increase
      of perforations detected with the water inflation test according to EN 455-1 was
      found for brand E. As gloves of brand C and D became tacky after 10
      disinfections, they were inappropriate for manual work. As a result, disinfection
      with isopropanol 60% (v/v) can be recommended for gloves of brand A and B only.
      Disinfection of these gloves is admissible e.g. after indirect patient contact,
      taking blood samples or laboratory work if no visible contamination or
      perforation has occurred. However, after contact with patients suffering from an
      infectious disease or carrying multiresistant organisms the gloves have to be
      changed. The same holds true if the gloves might be contaminated with naked
      viruses (e.g. Poliomyelitis virus), since virucidal alcoholic hand disinfectants
      require high concentration thus leading to materials incompatibility.

PMID- 10084209
TI  - Etiological factors of avascular necrosis of the femoral head. Twenty years
      later.

PMID- 10084210
TI  - Coagulopathies and osteonecrosis.
AB  - Intravascular coagulation of the intraosseous microcirculation (capillaries and
      venous sinusoids) progressing to generalized venous thrombosis, and less commonly
      retrograde arterial occlusion, now appears to be the cause of nontraumatic
      osteonecrosis. However, this coagulopathy is only an intermediary event, which is
      always activated by some underlying etiologic risk factor(s). Conditions capable
      of triggering intravascular coagulation include familial thrombophilia
      (resistance to activated protein C, decreased protein C, protein S, or
      antithrombin III), hyperlipemia and embolic lipid (alcoholism and
      hypercortisonism), hypersensitivity reactions (allograft organ rejection, immune
      complexes, and antiphospholipid antibodies), bacterial endotoxic (Shwartzman)
      reactions and various viral infections, proteolytic enzymes (pancreatitis),
      tissue factor release (inflammatory bowel disease, malignancies, neurotrauma, and
      pregnancy), and other prothrombotic and hypofibrinolytic conditions.

PMID- 10084211
TI  - [Bone and joint manifestations of sickle cell anemia].

PMID- 10084212
TI  - Cell biology during repair of osteonecrosis: implications for rational treatment.

PMID- 10084213
TI  - [Pathogenesis of non-traumatic femoral head osteonecrosis].

PMID- 10084214
TI  - [Value of scintigraphic study combining the vascular phase of nanocolloids and
      the osseous phase of diphosphonates in the diagnosis of ischemic osteonecrosis].

PMID- 10084215
TI  - [Value of the functional investigation of the bone: intramedullary pressure
      measurement, trans-osseus phlebography and needle biopsy].

PMID- 10084216
TI  - Classification of avascular necrosis: a comparative study.

PMID- 10084217
TI  - [Natural development of non-traumatic osteonecrosis of the hip].

PMID- 10084218
TI  - Cortical bone allografting in femoral head necrosis.
AB  - Ten femoral heads (six patients) with avascular necrosis were operated on using a
      fibular allograft. The procedure included core decompression followed by
      insertion of a cortical bone graft in order to relieve mechanical stresses from
      the overlying subchondral bone. The presence of the supporting graft should avoid
      an expected collapse or prevent its worsening if already present. A freeze-dried
      and processed cortical bone allograft was preferred to an autograft.
      Weightbearing was normally and fully resumed at the second postoperative month.
      There were three failures within the first year, four satisfactory results, in
      which the hip was replaced after 4 years while there are still 3 hips that have
      been preserved from arthroplasty in young patients after 5 years. The technique
      is easy and able to substantially delay an arthroplasty in an active patient.

PMID- 10084219
TI  - [Free autologous iliac graft in femoral head osteonecrosis].
AB  - Failures of hip arthroplasties in younger patients led us to choose, in Steinberg
      III and IV stages, a resection of the necrosis and a "filling in" with a free
      autologous cancellous iliac graft. Indications for an iliac graft are the
      necrosis at Steinberg III and IV stages, with a Kerboull angle inferior to 180
      degrees, a necrotic depth inferior to 1.5 cm, in patients under 55. Its
      advantages allow to avoid the microsurgical techniques of vascularized grafts and
      the complications of a possible secondary arthroplasty, as it sometimes occurs
      after an osteotomy. The long period of non-weightbearing after the graft is a
      relative inconvenient well tolerated by younger patients. However, the number of
      cases is still not sufficient to be statistically significant. Good results are
      maintained after 6 to 15 years.

PMID- 10084220
TI  - The surgical treatment of osteonecrosis of the femoral head with an osteochondral
      allograft.

PMID- 10084221
TI  - [Varus-flexion osteotomy in avascular femoral head osteonecrosis].

PMID- 10084222
TI  - Late follow-up of femoral head avascular necrosis managed by intertrochanteric
      osteotomy & bone grafting.
AB  - A prospective study was carried out on fifty hips in forty-eight patients with
      Ficat stage III (Steinberg stage IV) avascular necrosis (head deformity evident
      on plain x-ray) involving the supero-ventral segment. Mean age was 33 +/- 8 years
      (mean and standard deviation). There were thirty-six male and twelve female
      patients. Followup was 3-14 years (mean 8 years). This study precluded patients
      who were more than 45 years old, had an underlying condition requiring continued
      chemotherapy or cortisone, who had extensive dorsal (posterior) head segment
      involvement or those who were poorly motivated. Avascular necrosis was associated
      with alcohol in 35% of hips, trauma in 26% and 39% were idiopathic. One pregnancy
      related case was included in the latter subgroup. Curettage of the avascular
      segment and impaction of the bone graft was performed via subcapital fenestration
      of the anterior femoral neck. Pain was the presenting symptom in all cases. The
      mean pre-operative Harris hip score was 36 points and the mean score at last
      assessment was 87 points. Seven hips (14%) failed, failure implied conversion to
      a hip replacement or a Harris hip score of less than 70 points. Failures were
      seen within the first 3 years after osteotomy. Kaplan Meyer Survivorship analysis
      demonstrated an overall survivorship probability of 86% at 14 years. One patient
      died 10 years post surgery, the head was retrieved for histological study.
      Statistical study (Mann-Whitney U test) was carried out to determine factors
      related to failure. Of significance were age of the patient at time of osteotomy,
      contralateral hip involvement and size of the lesion. X ray studies of the
      femoral head included measurement of the necrotic angle, evaluation of
      restoration and maintenance of head contour and graft incorporation or
      stabilisation. Subsequent CAT scan studies enabled accurate quantification and
      siting of the avascular segment. Secondary x ray degenerative changes of the
      joint tended to manifest with time but these changes had little bearing on the
      clinical outcome. Osteotomy does have a measure of unpredictability, but in the
      appropriate case a high incidence of satisfactory results would be anticipated.

PMID- 10084223
TI  - [Avascular femoral head necrosis, treatment with bipolar prostheses].

PMID- 10084224
TI  - [Total prosthesis in avascular femoral head osteonecrosis].

PMID- 10084225
TI  - [Treatment of hip necrosis by sequestrectomy and replacement with bone cement].

PMID- 10084226
TI  - [Femoral head osteonecrosis: original extra-articular cementoplasty technique. A
      series of 20 cases].

PMID- 10084227
TI  - [Vertebral necrosis].

PMID- 10084228
TI  - [Incidence of humeral head osteonecrosis after fracture of the superior end of
      the humerus].

PMID- 10084229
TI  - [Role of arthroscopy in shoulder osteonecrosis].

PMID- 10084230
TI  - [Grammont prosthesis in humeral head osteonecrosis. Indications--results].

PMID- 10084231
TI  - [Natural development and indications for surgical treatment of femoral condyle
      osteonecrosis].

PMID- 10084232
TI  - [Use of needle biopsy in femoral condyle osteonecrosis].

PMID- 10084233
TI  - [Role of arthroscopy in knee joint osteonecrosis].

PMID- 10084234
TI  - The use of lateral patellar autologous grafts for the repair of large
      osteochondral defects in the knee.

PMID- 10084235
TI  - Repair of osteochondral defects with autogenous callo-osseous grafts.
AB  - A new method of biological repair of osteochondral defects is presented. An
      osteochondral defect in the rabbit knee was reconstructed with an autogenous
      callo-osseous graft made of a superficial sheet of medullary fracture callus
      attached to a base of cancellous bone. The reparative tissues were evaluated for
      24 weeks by histology, analysis of uronic acid contents, and immunohistochemical
      staining of collagen constituents. The callo-osseous graft provided significantly
      faster and better repair of the articular surface than an untreated defect or a
      callo-osseous graft in which the cells had been devitalized by irradiation prior
      to transplantation. The results indicate that the callo-osseous graft contributes
      to the repair process via providing both favorable extracellular matrices and
      pluripotential mesenchymal cells.

PMID- 10084236
TI  - [Osteonecrosis of the knee].

PMID- 10084237
TI  - [Indications and results of arthroplasties in the treatment of femoral condyle
      osteonecrosis].

PMID- 10084238
TI  - Prospective study of intentional weight loss and mortality in overweight white
      men aged 40-64 years.
AB  - Although 25% of US men indicate that they are trying to lose weight, the
      association between intentional weight loss and longevity in men is unknown. The
      authors analyzed prospective data from 49,337 overweight (initial body mass index
      > or =27) white men aged 40-64 years who, in 1959-1960, answered questions on
      weight change direction, amount, time interval, and intent. Vital status was
      determined in 1972. Proportional hazards regression estimated mortality rate
      ratios for men who intentionally lost weight compared with men with no weight
      change. Analyses were stratified by health status and adjusted for age, initial
      body mass index, smoking status, alcohol intake, education, physical activity,
      health history, and physical symptoms. Among men with no reported health
      conditions (n = 36,280), intentional weight loss was not associated with total,
      cardiovascular (CVD), or cancer mortality, but diabetes-associated mortality was
      increased 48% (95% confidence interval (CI) -7% to +133%) among those who lost 20
      pounds (9.1 kg) or more; this increase was largely related to non-CVD mortality.
      Among men with reported health conditions (n = 13,057), intentional weight loss
      had no association with total or CVD mortality, but cancer mortality increased
      25% (95% confidence interval -4% to +63%) among those who lost 20 pounds or more.
      Diabetes-associated mortality was reduced 32% (95% confidence interval -52% to 
      5%) among those who lost less than 20 pounds and 36% (95% confidence interval 
      49% to -20%) among those who lost more than 20 pounds. These results and those
      from our earlier study in women (Williamson et al., Am J Epidemiol 1995;141:1128
      41) suggest that intentional weight loss may reduce the risk of dying from
      diabetes, but not from CVD. In observational studies, however, it is difficult to
      separate intentional weight loss from unintentional weight loss due to
      undiagnosed, underlying disease. Well-designed observational studies, as well as
      randomized controlled trials, are needed to determine whether intentional weight
      loss reduces CVD mortality.

PMID- 10084239
TI  - Prospective study of intentionality of weight loss and mortality in older women:
      the Iowa Women's Health Study.
AB  - Several epidemiologic investigations have suggested that weight loss is
      associated with increased mortality risk but have not examined whether the weight
      loss was intentional or unintentional. The authors examined whether the
      association between weight loss and mortality differs by whether the weight loss
      was intentional or unintentional as part of the Iowa Women's Health Study, a
      prospective cohort study of health risk factors in postmenopausal women. Women
      aged 55-69 years completed questions about intentional and unintentional weight
      losses since age 18 years via mail survey in 1992 and were followed through 1995.
      One or more intentional weight loss episodes of 20 or more pounds (> or =9.1 kg)
      during adulthood was not significantly associated with higher total or
      cardiovascular disease mortality risk compared with never losing > or =20 pounds.
      One or more unintentional weight loss episodes of 20 or more pounds was
      associated with a 26-57% higher total mortality risk and a 51-114% higher
      cardiovascular disease mortality risk, compared with never losing 20 or more
      pounds. Associations between unintentional weight loss and increased mortality
      risk were confined mostly to women with prevalent disease, hypertension, or
      diabetes. Patterns of association did not vary by overweight status. These
      findings suggest that the association between weight loss and increased mortality
      risk observed in epidemiologic studies may be due to unintentional weight loss
      that reflects existing disease and not due to intentional weight loss.

PMID- 10084240
TI  - Invited commentary on "Prospective study of intentionality of weight loss and
      mortality in older women: the Iowa Women's Health Study" and "Prospective study
      of intentional weight loss and mortality in overweight white men aged 40-64
      years.".

PMID- 10084241
TI  - Hypertension, antihypertensive medication use, and risk of renal cell carcinoma.
AB  - To investigate whether diuretic medication use increases risk of renal cell
      carcinoma (RCC), the authors conducted a case-control study of health maintenance
      organization members in western Washington State. Cases (n = 238) diagnosed
      between January 1980 and June 1995 were compared with controls (n = 616) selected
      from health maintenance organization membership files. The computerized health
      maintenance organization pharmacy database provided information on medications
      prescribed after March 1977. Additional exposure information was collected from
      medical records. For women, use of diuretics was associated with increased risk
      of RCC (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.0-3.1), but the
      association was not independent of a diagnosis of hypertension (adjusted for
      hypertension, OR = 1.1, 95% CI 0.5-2.1). Similarly, nondiuretic antihypertensive
      use was associated with increased risk, but only when unadjusted for
      hypertension. For men, neither diuretic nor nondiuretic antihypertensive use was
      associated with risk of RCC. A diagnosis of hypertension was clearly associated
      with RCC risk for women (OR = 2.5, 95% CI 1.2-5.1), but not men (OR = 1.3, 95% CI
      0.7-2.5). High systolic and diastolic blood pressures were associated with
      increased risk in both sexes. These results do not support the hypothesis that
      use of diuretic medication increases RCC risk; they are more consistent with an
      association between RCC and high blood pressure.

PMID- 10084242
TI  - Dietary fat and coronary heart disease: a comparison of approaches for adjusting
      for total energy intake and modeling repeated dietary measurements.
AB  - Previous cohort studies of fat intake and risk of coronary heart disease (CHD)
      have been inconsistent, probably due in part to methodological differences and
      various limitations, including inadequate dietary assessment and incomplete
      adjustment for total energy intake. The authors analyzed repeated assessment of
      diet from the Nurses' Health Study to examine the associations between intakes of
      four major types of fat (saturated, monounsaturated, polyunsaturated, and trans
      fats) and risk of CHD during 14 years of follow-up (1980-1994) by using
      alternative methods for energy adjustment. In particular, the authors compared
      four risk models for energy adjustment: the standard multivariate model, the
      energy-partition model, the nutrient residual model, and the multivariate
      nutrient density model. Within each model, the authors compared four different
      approaches for analyzing repeated dietary measurements: baseline diet only, the
      most recent diet, and two different algorithms for calculating cumulative average
      diets. The substantive results were consistent across all models; that is, higher
      intakes of saturated and trans fats were associated with increased risk of CHD,
      while higher intakes of monounsaturated and polyunsaturated fats were associated
      with reduced risk. When nutrients were considered as continuous variables, the
      four energy-adjustment methods yielded similar associationS. However, the
      interpretation of the relative risks differed across models. In addition, within
      each model, the methods using the cumulative averages in general yielded stronger
      associations than did those using either only baseline diet or the most recent
      diet. When the nutrients were categorized according to quintiles, the residual
      and the nutrient density models, which gave similar results, yielded
      statistically more significant tests for linear trend than did the standard and
      the partition models.

PMID- 10084243
TI  - Agreement between drug treatment data and a discharge diagnosis of diabetes
      mellitus in the elderly.
AB  - The authors examined agreement between drug treatment data and a discharge
      diagnosis of diabetes, considered whether agreement was modified by demographic
      variables and measures of comorbidity, and evaluated construct validity through
      consideration of relations with subsequent mortality. The study sample comprised
      81,700 residents of New Jersey aged 65-99 years who had prescription drug
      coverage either through Medicaid or that state's Pharmacy Assistance for the Aged
      and Disabled program and had at least one hospitalization between July 1, 1989,
      and June 30, 1991. In this population, 16.4% filled a prescription for insulin or
      an oral hypoglycemic agent during the 120 days before admission, and 16.3% had a
      discharge diagnosis of diabetes. Overall agreement between these two indicators
      was modest (kappa = 0.67, 95% confidence interval 0.66-0.67) and was weaker in
      those aged 85 years and above (kappa = 0.58, 95% confidence interval 0.56-0.60),
      those in nursing homes (kappa = 0.42, 95% confidence interval 0.39-0.44), and
      those with a high level of comorbidity (modified Charlson index > or =5; kappa =
      0.59, 95% confidence interval 0.56-0.62). Presence of a diagnosis of diabetes was
      associated with an apparent 24% reduction in the risk of death during the study
      interval (p<0.001), while prior treatment for diabetes had little relation to
      mortality (p = 0.15). These paradoxical associations with mortality and the lower
      agreement between discharge diagnoses and drug treatments associated with older
      age, nursing home residence, and comorbidity suggest limitations in the use of
      claims data to identify diabetes in the elderly.

PMID- 10084244
TI  - Caffeine consumption and menstrual function.
AB  - The relation between caffeine intake and menstrual function was examined in 403
      healthy premenopausal women who belonged to Kaiser Permanente Medical Care
      Program in 1990-1991. A telephone interview collected information about
      caffeinated beverage intake as well as other lifestyle, demographic,
      occupational, and environmental factors. 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, each cycle was
      characterized as anovulatory or ovulatory, and a probable day of ovulation was
      selected when appropriate. Logistic regression and repeated measures analyses
      were performed on menstrual parameters. Women whose caffeine consumption was
      heavy (>300 mg of caffeine per day) had less than a third of the risk for long
      menses (> or =8 days) compared with women who did not consume caffeine (adjusted
      odds ratio = 0.30, 95% confidence interval 0.14-0.66). Those whose caffeine
      consumption was heavy also had a doubled risk for short cycle length (< or =24
      days) (adjusted odds ratio = 2.00, 95% confidence interval 0.98-4.06); this
      association was also evident in those whose caffeine consumption was heavy who
      did not smoke (adjusted odds ratio = 2.11, 95% confidence interval 1.03-4.33).
      Caffeine intake was not strongly related to an increased risk for anovulation,
      short luteal phase (< or =10 days), long follicular phase (> or =24 days), long
      cycle (> or =36 days), or measures of within-woman cycle variability.

PMID- 10084245
TI  - HIV-1 incidence among opiate users in northern Thailand.
AB  - The incidence of human immunodeficiency virus type 1 (HIV-1) infection among
      opiate users was determined in a retrospective cohort of 436 patients with
      multiple admissions to the only inpatient drug treatment program in northern
      Thailand between October 1993 and September 1995. During 323.4 person-years of
      follow-up, 60 patients presenting for detoxification acquired HIV-1 infection,
      for a crude incidence rate of 18.6 per 100 person-years (95% confidence interval
      14.4-23.9). All seroconverters were male. HIV-1 incidence varied by the current
      route of drug administration: 31.3 per 100 person-years for injectors and 2.8 per
      100 person-years for noninjectors (smoking and ingestion). Significant
      differences were found by ethnicity: HIV-1 incidence was 29.3 per 100 person
      years for Thai lowlanders and 8.5 per 100 person-years for hill tribes.
      Multivariate relative risk estimates showed that injecting opiates (vs. use by
      other routes), being unmarried, being under age 40 years, being a Thai lowlander,
      having a primary and secondary education, and being employed in the business
      sector were each independently associated with human immunodeficiency virus
      seroconversion. This HIV-1 incidence rate is double that reported for Bangkok and
      suggests that prevention and control programs for drug users need to be expanded
      throughout Thailand. Improved availability of more-effective treatment regimens
      and increased access to sterile injection equipment are needed to confront the
      HIV-1 epidemic among opiate users in northern Thailand.

PMID- 10084246
TI  - Onchocerciasis and epilepsy: a matched case-control study in the Central African
      Republic.
AB  - The occurrence of epileptic seizures during onchocercal infestation has been
      suspected. Epidemiologic studies are necessary to confirm the relation between
      onchocerciasis and epilepsy. A matched case-control study was conducted in
      dispensaries of three northwestern towns of the Central African Republic. Each
      epileptic case was matched against two nonepileptic controls on the six criteria
      of sex, age (+/-5 years), residence, treatment with ivermectin, date of last
      ivermectin dose, and the number of ivermectin doses. Onchocerciasis was defined
      as at least one microfilaria observed in iliac crest skin snip biopsy. A total of
      561 subjects (187 cases and 374 controls) were included in the study. Of the
      epileptics, 39.6% had onchocerciasis, as did 35.8% of the controls. The mean
      dermal microfilarial load was 26 microfilariae per mg of skin (standard
      deviation, 42) in the epileptics and 24 microfilariae per mg of skin (standard
      deviation, 48) in the controls. This matched case-control study found some
      relation (odds ratio = 1.21, 95% confidence interval 0.81-1.80), although it was
      nonstatistically significant.

PMID- 10084247
TI  - Inverse graded relation between alcohol consumption and active infection with
      Helicobacter pylori.
AB  - Alcoholic beverages are known to have strong antibacterial activity. It is
      unclear, however, to what degree their consumption affects colonization of the
      human stomach with the bacterium Helicobacter pylori, a risk factor of various
      chronic diseases. The authors assessed the relation between alcohol consumption
      and active infection with H. pylori in a cross-sectional study among employees of
      a health insurance company and their household members (n = 425) in southern
      Germany. Quantitative information on alcohol consumption by beverage type and
      other factors that were known or suspected to be related to infection status was
      collected by a standardized questionnaire, and active infection was measured by
      the 13C-urea breath test. After control for confounding factors, there was a
      monotonic inverse graded relation between alcohol consumption and H. pylori
      infection (p for trend = 0.017). The odds ratio of infection among subjects who
      consumed more than 75 g of alcohol per week compared with subjects who did not
      drink alcohol was 0.31 (95 percent confidence interval 0.12-0.81). The inverse
      relation with H. pylori infection was stronger for alcohol consumed in the form
      of wine than for alcohol from beer. Notwithstanding its cross-sectional design,
      this study seems to support the hypothesis that alcohol consumption, particularly
      wine consumption, may reduce the odds of active infection with H. pylori.

PMID- 10084248
TI  - Place effects for areas defined by administrative boundaries.
AB  - This study estimates the effects of place on the distribution of health problems,
      health-related quality of life, general well-being, and family functioning for
      youths and adults aged 12 years and older. Data come from the Ontario Health
      Survey, a cross-sectional study done in 1990 to provide baseline statistical data
      on population health within 42 public health units throughout the province. Place
      effects were generally small and were influenced by both the size of the
      geographic area used to define place and the health indicator selected for study.
      Variations in health explainable at the public health region level were less than
      1%. Variations in health explainable within smaller geographic boundaries
      (enumeration areas) ranged from 4.7% for health problems to 0.2% for family
      functioning. Adjustment for area differences in the age, gender, education,
      marital status, income, and birthplace of inhabitants reduced these place effects
      at the enumeration area level to 3.7% for health problems and to less than 0.1%
      for family functioning. The lack of evidence for place effects within large
      jurisdictional boundaries raises questions about both the usefulness of carrying
      out health needs assessment surveys within these areas and the informativeness of
      these geographic boundaries for studying place effects.

PMID- 10084249
TI  - Evaluation of the quality of an injury surveillance system.
AB  - The sensitivity, positive predictive value, and representativeness of the
      Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were
      assessed. Sensitivity was estimated at four centers in June through August 1992,
      by matching independently identified injuries with those in the CHIRPP database.
      The positive predictive value was determined by reviewing all "injuries" in the
      database (at Montreal Children's Hospital) that could not be matched.
      Representativeness was assessed by comparing missed with captured injuries (at
      Montreal Children's Hospital) on demographic, social, and clinical factors.
      Sensitivity ranged from 30% to 91%, and the positive predictive value was 99.9%
      (i.e., the frequency of false-positive capture was negligible). The
      representativeness study compared 277 missed injuries with 2,746 captured
      injuries. The groups were similar on age, sex, socioeconomic status, delay before
      presentation, month, and day of presentation. Injuries resulting in admissions,
      poisonings, and those presenting overnight were, however, more likely to be
      missed. The adjusted odds ratio of being missed by CHIRPP for admitted injuries
      (compared with those treated and released) was 13.07 (95% confidence interval
      7.82-21.82); for poisonings (compared with all other injuries), it was 9.91 (95%
      confidence interval 5.39-18.20); and for injuries presenting overnight (compared
      with those presenting during the day or evening), it was 4.11 (95% confidence
      interval 3.11-5.44). These injuries were probably missed because of inadequate
      education of participants in the system. The authors conclude that CHIRPP data
      are of relatively high quality and may be used, with caution, for research and
      public health policy.

PMID- 10084250
TI  - Cytokine treatment or accessory cells are required to initiate engraftment of
      purified primitive human hematopoietic cells transplanted at limiting doses into
      NOD/SCID mice.
AB  - Little is known about the cell types or mechanisms that underlie the engraftment
      process. Here, we have examined parameters affecting the engraftment of purified
      human Lin-CD34+CD38- normal and AML cells transplanted at limiting doses into
      NOD/SCID recipients. Mice transplanted with 500 to 1000 Lin-CD34+CD38- cord blood
      (CB) or AML cells required the co-transplantation of accessory cells (ACs) or
      short-term in vivo cytokine treatment for engraftment, whereas transplantation of
      higher doses (>5000 Lin-CD34+CD38- cells) did not show these requirements
      suggesting that ACs are effective for both normal and leukemic stem cell
      engraftment in this model. Mature Lin+CD34- and primitive Lin-CD34+CD38+ cells
      were capable of acting as ACs even though no repopulating cells are present.
      Cytokine treatment of NOD/SCID mice could partially replace the requirement for
      co-transplantation of AC. Furthermore, no difference was seen between the
      percentage of engrafted mice treated with cytokines for only the first 10 days
      after transplant compared to those receiving cytokines for the entire time of
      repopulation. Surprisingly, no engraftment was detected in mice when cytokine
      treatment was delayed until 10 days posttransplant. Together, these studies
      suggest that the engraftment process requires pluripotent stem cells plus
      accessory cells or cytokine treatment which act early after transplantation. The
      NOD/SCID xenotransplant system provides the means to further clarify the
      processes underlying human stem cell engraftment.

PMID- 10084251
TI  - Comparative study of the in vitro behavior of cord blood subpopulations after
      short-term cytokine exposure.
AB  - We investigated the effect of short-term cytokine exposure on defined cord blood
      subpopulations. CD34+Thy1+, CD34+Thy1-, CD34+38-, CD34+38+, CD34+DR+, CD34+DR-,
      CD34+Rhodamine123 (Rh123)- and CD34+Rh123+ cells were incubated for 7 days in
      IMDM + 10% FCS + IL3 + IL6 + G-CSF + SCF (36GS) + flt3L. We evaluated LTHC-IC,
      immunophenotype and nucleated cell count for each cell population before and
      after cytokine exposure. Short-term exposure of CD34+38+, CD34+Thy1-, CD34+DR+,
      CD34+DR- and CD34+Rh123+ cells to 36GS causes a significant increase in cell
      number, whereas CD34+38-, CD34+Thy1+, and CD34+Rh123- cells show only a limited
      increase. CD34 status post cytokine incubation shows that CD34+38+, CD34+Thy1-,
      CD34+DR+, and CD34+Rh123+ fractions have a lower proportion of cells remaining
      CD34+ than CD34+38- CD34+Thy1+, CD34+DR- and CD34+Rh123- fractions. LTHC-IC
      analyses among input subpopulations show a higher frequency among CD34+38+,
      CD34+Thy1-, CD34+DR+, CD34+DR- and CD34+Rh123+ cells as compared with CD34+38-,
      CD34+Thy1+ and CD34+Rh123- cells. However, when LTHC-IC were evaluated after
      cytokine exposure, CD34+38-, CD34+Thy1+, and CD34+Rh123- cells showed a higher
      frequency of LTHC-IC as compared with other subpopulations. Addition of flt3L to
      36GS doubled the numbers in all subpopulations without altering the proportion of
      CD34+ cells. Results suggest that CD34+38-, CD34+Thy1+ and CD34+Rh123- cells have
      a limited proliferative response to cytokines, the stem cell component of these
      populations is largely maintained and that expansion is derived from mature cell
      populations.

PMID- 10084252
TI  - Early harvest and late transplantation as an effective therapeutic strategy in
      multiple myeloma.
AB  - Transplantation after high-dose chemotherapy prolongs survival in patients with
      multiple myeloma compared with standard therapy. It is unclear whether the
      optimal timing of transplantation is immediately after induction chemotherapy or
      whether stem cells may be cryopreserved for transplantation at subsequent
      progression or relapse. In this study, stem cells were collected within 6 months
      of diagnosis, followed by transplantation only at progression of myeloma. One
      hundred and eighteen patients with multiple myeloma had stem cells collected and
      cryopreserved. Eleven had transplants early in the disease after they
      demonstrated failure to respond to primary therapy. The remaining 107 were
      eligible for transplants when there was evidence of progressive disease. Of the
      118 patients, 67 had transplants, nine died of progressive disease before
      transplantation, and 42 remain alive in plateau phase. The median survival of the
      group is 58.5 months; 67 are alive. Serum beta2-microglobulin, bone marrow
      labeling index (S phase), and hemoglobin level predicted overall survival (P <
      0.006, P < 0.001, and P < 0.01, respectively). We conclude that early
      cryopreservation of blood stem cells followed by transplantation at progression
      is a feasible approach to therapy in patients with myeloma. The underlying
      biology of the disease has a greater impact on survival than the timing of
      transplantation. A prospective randomized trial is required to answer
      definitively the question of the optimal timing of blood cell transplantation.

PMID- 10084253
TI  - High-dose therapy with autologous or allogeneic transplantation as salvage
      therapy for small cleaved cell lymphoma of follicular center cell origin.
AB  - Between 1985 and 1996, 51 patients with relapsed or refractory small cleaved cell
      lymphoma (SCCL) received high-dose chemotherapy +/- TBI in conjunction with
      autologous (ABMT) (36 patients) or allogeneic transplantation (15 patients).
      Patients were eligible for ABMT if the bone marrow biopsy done prior to the
      planned transplant did not reveal microscopic involvement with SCCL. Patients
      receiving ABMT had a median age of 48 years, had received a median of 2.5
      chemotherapy regimens prior to transplantation, and were transplanted a median of
      35.5 months from diagnosis. Among patients receiving ABMT, 5 year actuarial
      survival was 56+/-11%. Median survival was 126+ months, and median survival from
      diagnosis was 191 months. Univariate and multivariate analysis identified
      sensitive disease as the best predictor of a favorable response. Five-year
      actuarial survival was 66+/-12% for patients with sensitive disease at the time
      of transplant as compared to 29+/-17% for patients with resistant disease, P =
      0.015. Median survival in patients with sensitive disease at the time of ABMT was
      126+ months. By univariate analysis, survival was significantly better for
      patients receiving ABMT as compared to patients receiving allogeneic transplants.
      Median survival following allogeneic transplantation was 5 months; 5 year
      actuarial survival was 15+/-13%. In a multivariate analysis, which considered
      autologous vs allogeneic transplantation, sensitive vs resistant disease, <3 vs >
      or = 3 prior treatments, and prior bone marrow involvement, allogeneic
      transplantation was significantly associated with poor survival. Treatment
      related mortality occurred in eight of 15 patients receiving allogeneic
      transplantation and limited the effectiveness of this therapy. High-dose therapy
      in conjunction with ABMT is effective therapy for patients with SCCL whose
      disease is sensitive to chemotherapy and whose marrows are microscopically free
      of disease. Because of possible selection bias, it has not been proven that this
      approach increases survival in these patients. Treatment-related mortality limits
      the effectiveness of allogeneic transplantation in SCCL.

PMID- 10084254
TI  - Autologous transplantation of chemotherapy-purged PBSC collections from high-risk
      leukemia patients: a pilot study.
AB  - We have recently demonstrated that the combination of the alkylating agent
      nitrogen mustard (NM) and etoposide (VP-16) is capable of eliminating, ex vivo,
      leukemic cells contaminating PBSC collections and this is associated with a
      significant recovery of primitive and committed hematopoietic progenitor cells.
      Based on these data a pilot study on autologous transplantation of NM/VP-16
      purged PBSC for high-risk leukemic patients was recently initiated. Twelve
      patients (seven females and five males) with a median age of 46 years (range 18
      57) have been treated. Two patients had acute myeloblastic leukemia (AML)
      resistant to conventional induction treatment, four patients had secondary AML in
      I complete remission (CR), one patient was in II CR after failing a previous
      autologous BM transplantation, while two additional AML individuals were in I CR
      achieved after three or more cycles of induction treatment. Two patients with
      high-risk acute lymphoblastic leukemia (ALL) in I CR and one patient with mantle
      cell lymphoma and leukemic dissemination were also included. Eight patients
      showed karyotypic abnormalities associated with a poor clinical outcome. The
      mobilizing regimens included cytosine arabinoside and mitoxantrone with (n = 6)
      or without fludarabine (n = 3) followed by subcutaneous administration of G-CSF
      (5 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3)
      (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection
      of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3)
      and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20
      microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of
      steady-state BM CFU-GM) of NM of 0.7 microg/ml (range 0.25-1.25). Eleven patients
      were reinfused after busulfan (16 mg/kg) and Cy (120 mg/kg) conditioning with a
      median residual dose of 0.3 x 10(4) CFU-GM/kg (0-11.5). The median time to
      neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range
      12-59); the median time to platelet transfusion independence (>20 and >50 x
      10(9)/l) was 40 days (18-95) and 69 days (29-235), respectively. Hospital
      discharge occurred at a median of 25 days (18-58) after stem cell reinfusion.
      Four individuals are alive in CR (n = 3) or with residual nodal disease (n = 1
      lymphoma patient) with a follow-up of 32, 26, 3 and 14 months, respectively.
      Seven patients died due to disease progression or relapse (n = 5) or
      extrahematological transplant toxicity (n = 2). Our data suggest that
      pharmacological purging of leukapheresis collections of leukemic patients at high
      risk of relapse is feasible and ex vivo treated cells reconstitute autologous
      hematopoiesis.

PMID- 10084255
TI  - Single leukapheresis products collected from healthy donors after the
      administration of granulocyte colony-stimulating factor contain ten-fold higher
      numbers of long-term reconstituting hematopoietic progenitor cells than
      conventional bone marrow allografts.
AB  - Cytokine-mobilized peripheral blood progenitor cells (PBPCs) have been used
      successfully for hematopoietic reconstitution following allogeneic
      transplantation. The ease of harvest, the faster engraftment and the high yield
      of CD34+ cells have made this source of hematopoietic progenitor cells (HPCs) an
      attractive alternative to bone marrow (BM). In the present study we compared the
      engraftment potential of conventional BM allografts and single leukapheresis
      products (LPs) collected from healthy donors following the administration of
      granulocyte colony-stimulating factor (G-CSF). For this, lineage-committed and
      primitive HPCs were assessed by flow cytometry and by colony- and cobblestone
      area-forming cell (CFC, CAFC) assays. Mean numbers of CD34+ cells in LPs (n = 11)
      were similar to that of BM grafts (n = 12) (278+/-57 vs 227+/-34 x 10(6) CD34+
      cells). The frequencies of CFCs, week 5 CAFCs and week 8 CAFCs were 1.6-, 8.4-
      and 10.3-fold higher in the CD34+ compartment of mobilized blood than that of
      marrow, resulting in significantly higher yields of clonogenic HPCs in LPs when
      compared to BM grafts. We conclude that G-CSF preferentially mobilizes clonogenic
      progenitors capable of short- and, in particular, longterm reconstitution, and
      that the engraftment potential of single LPs is superior to that of BM
      allografts. Hence, the use of PBPCs may be favorable for protocols that include
      graft manipulations with expected cell loss (eg T cell depletion, CD34+
      selection). PBPCs may also be advantageous for gene therapy trials due to their
      high numbers of potential target cells (eg CAFCs).

PMID- 10084256
TI  - B cell lymphoproliferative disorders following hematopoietic stem cell
      transplantation: risk factors, treatment and outcome.
AB  - Twenty-six cases of B cell lymphoproliferative disorder (BLPD) were identified
      among 2395 patients following hematopoietic stem cell transplants (HSCT) for
      which an overall incidence of BLPD was 1.2%. The true incidence was probably
      higher, since 9/26 of the diagnoses were made at autopsy. No BLPD was observed
      following autologous HSCT, so risk factor analyses were confined to the 1542
      allogeneic HSCT. Factors assessed were HLA-mismatching (> or = 1 antigen), T cell
      depletion (TCD), presence of acute GvHD (grades II-IV), donor type (related vs
      unrelated), age of recipient and donor, and underlying disease. Factors found to
      be statistically significant included patients transplanted for immune deficiency
      and CML, donor age > or = 18 years, TCD, and HLA-mismatching, with recipients of
      combined TCD and HLA-mismatched grafts having the highest incidence. Factors
      found to be statistically significant in a multiple regression analysis were TCD,
      donor age and immune deficiency, although 7/8 of the patients with
      immunodeficiencies and BLPD received a TCD graft from a haploidentical parent.
      The overall mortality was 92% (24/26). One patient had a spontaneous remission,
      but subsequently died >1 year later of chronic GVHD. Thirteen patients received
      therapy for BLPD. Three patients received lymphocyte infusions without response.
      The only patients with responses and longterm survival received alpha interferon
      (alphaIFN). Of seven patients treated with alphaIFN there were four responses
      (one partial and three complete). These data demonstrate that alphaIFN can be an
      effective agent against BLPD following HSCT, if a timely diagnosis is made.

PMID- 10084257
TI  - Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the
      uterus after total body irradiation and allogeneic bone marrow transplantation in
      childhood.
AB  - Internal genitalia and uterine blood flow were assessed by ultrasound in 12
      females 4.0-10.9 years after total body irradiation and allogeneic bone marrow
      transplantation for childhood leukaemia or lymphoma. Median age of the
      participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and
      21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered
      puberty and 11/12 females had experienced the menarche. Eight females received
      sex steroid replacement therapy, three had spontaneous pubertal development and
      one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian
      volumes were significantly reduced to -2.6 standard deviation scores (SDS) (-6.3
      to -0.6), P = 0.002, and -2.6 SDS (-4.8 to -0.5), P = 0.002, respectively,
      compared with normal controls. Follicles were only detectable in two individuals.
      Uterine blood flow was impaired, as a systolic blood flow could be measured in
      6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate
      that the prescribed dosage of hormone replacement therapy, which was sufficient
      to induce bleeding and suppress other stigmata of premature menopause, was
      inadequate to generate normal uterine growth. In order to achieve uterine growth
      higher doses of hormone replacement therapy may be required. Our results confirm
      pelvic ultrasound as a reliable tool for investigation of internal female
      genitalia; however, in an infertility setting further tests are indicated.

PMID- 10084258
TI  - Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant
      patients receiving chemotherapy and total body irradiation.
AB  - Few trials exist regarding the antiemetic efficacy of granisetron in bone marrow
      transplant (BMT) recipients conditioned with high-dose chemotherapy and total
      body irradiation (TBI). In this single-center, open-label, prospective, trial,
      the antiemetic efficacy and safety of granisetron plus dexamethasone were
      evaluated in 26 patients conditioned with cyclophosphamide-containing regimens
      (the majority receiving 60 mg/kg per day on 2 consecutive days), and TBI (12 Gy
      divided over 4 days). Daily intravenous doses of granisetron 1 mg plus
      dexamethasone 10 mg were given 30 min prior to chemotherapy or radiation, and
      continued for 24 h after the last conditioning treatment for a median of 6 days
      (range 3-9). Emetic control was defined by the number of emetic episodes
      occurring within a 24 h period, or the requirement for rescue medication for
      nausea or vomiting. A total of 25 patients completed 186 evaluable treatment
      days. Response (emetic control by treatment days) was complete in 50% of
      patients, major in 48%, minor in 2%, and there were no failures. Adverse effects
      were minor, with diarrhea (15%), headache (14%), and constipation (11%) reported
      most often. Based on these results, the antiemetic regimen of granisetron plus
      dexamethasone appears effective and well tolerated during BMT conditioning with
      high-dose cyclophosphamide and TBI.

PMID- 10084259
TI  - Bloodstream infections can develop late (after day 100) and/or in the absence of
      neutropenia in children receiving allogeneic bone marrow transplantation.
AB  - We retrospectively evaluated the incidence and time from transplantation of
      bloodstream infections occurring in children receiving bone marrow transplant
      (BMT) at G Gaslini Children's Hospital between September 1984 and December 1997.
      During this period the incidence was 35% after allogeneic and 26% after
      autologous BMT (P=0.08). Among these episodes, 38% after allogeneic BMT and 90%
      after autologous BMT were detected in the presence of neutropenia within the
      first 30 days from reinfusion (P < 0.001). Incidence of catheter-related
      bloodstream infections was 40% after allogeneic and 8% after autologous BMT (P <
      0.001). Bloodstream infections in the absence of neutropenia were 55% after
      allogeneic BMT vs 10% after autologous BMT (P < 0.001) and occurred later after
      reinfusion (mean 199 vs 41 days, P <0.001). Among the episodes occurring after
      allogeneic BMT and in the absence of neutropenia, 61% were related to the
      presence of a central venous catheter, 15% were related to the presence of GVHD,
      but 23% were not associated with any of major risk factors for infection.
      Finally, 38% of episodes following allogeneic BMT were detected after day 100 vs
      1% after autologous BMT. We concluded that patients receiving allogeneic BMT
      experience a high incidence of bloodstream infections in the absence of
      neutropenia and that a significant proportion of these episodes is not clearly
      associated with well known risk factors such as GVHD or central venous catheters.
      Moreover, many episodes develop a long time after the transplantation procedure.
      Therefore, any febrile episode following allogeneic BMT even late and/or in the
      absence of neutropenia should be intensively managed.

PMID- 10084260
TI  - Adenovirus infection after pediatric bone marrow transplantation.
AB  - Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow
      transplants (BMT) at St Jude Children's Research Hospital between November 1990
      and December 1994 identified 6% (seven male, six female) with adenovirus
      infection. The affected patients had a median age of 7.9 years (range 3-24 years)
      at time of transplantation. Although transplants were performed for hematologic
      malignancies, solid tumors or nonmalignant conditions, only patients with
      hematologic malignancies had adenoviral infections. Adenovirus was first detected
      at a median of 54 days (range -4 to +333) after BMT. Adenovirus developed in
      eight of 69 (11.6%) patients receiving grafts from matched unrelated or
      mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched
      siblings, and in one of 93 (1.1%) receiving autografts. The most common
      manifestation of adenovirus infection was hemorrhagic cystitis, followed by
      gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus
      infection in pediatric BMT patients at our institution is similar to that
      reported in adult patients. Using univariate analysis, use of total body
      irradiation and type of bone marrow graft were significant risk factors for
      adenovirus infection. Only use of total body irradiation remained as a factor on
      multiple logistic regression analysis.

PMID- 10084261
TI  - Fungal prophylaxis by reduction of fungal colonization by oral administration of
      bovine anti-Candida antibodies in bone marrow transplant recipients.
AB  - Candida overgrowth and invasion constitute a serious threat with a high mortality
      in BMT recipients. Currently available topical antifungal prophylaxis is largely
      ineffective, and as resistance to existing, absorbable drugs for systemic use is
      rapidly developing, new forms of therapy are needed. We investigated the effect
      of oral treatment of BMT recipients with a bovine immunoglobulin product derived
      from animals immunized against several Candida species. The natural Candida
      colonization was first followed in 19 patients to establish the colonization
      pattern. Half of the patients were found to be colonized prior to transplantation
      and altogether 72% were colonized at some point during follow-up. Those with a
      high pre-transplant concentration of Candida in saliva (>100 CFU/ml) remained
      colonized throughout the BMT treatment period. The therapeutic effect was
      monitored in two other patient groups. The first group consisted of nine
      patients, where, due to a low number of primary colonized patients, response in
      colonized patients was suggestive of a therapeutic effect. In the second group,
      10 patients with a high level of colonization (>100 CFU/ml) were given 10 g daily
      of the product in three divided doses. The results suggest a treatment-related
      reduction in Candida colonization in a majority (7/10) of patients and one
      patient became completely negative. As no adverse effects were noted, our
      findings encourage additional studies in immunocompromised, transplant patients.

PMID- 10084262
TI  - Feasibility of finding an unrelated bone marrow donor on international registries
      for New Zealand patients.
AB  - Allogeneic bone marrow transplantation is the treatment of choice for several
      hematological conditions. Unfortunately, for the majority (70%) of patients an
      HLA-matched sibling donor is not available and a matched unrelated donor must be
      found if they are to proceed to allogeneic transplantation. Most of the donors on
      international registries are of Caucasian ethnic origin. It has been recognized
      that patients from certain racial groups have a reduced chance of finding an
      unrelated donor. This study reports the feasibility of finding an unrelated donor
      for our local New Zealand patients of Caucasian, New Zealand Maori and Pacific
      Islander ethnic origin presenting with transplantable hematological conditions at
      a single center. The search was performed on international registries using HLA
      A,B and DR typings for our patients. Six of six and five of six matches were
      evaluated. We have shown that Maori and Pacific Islanders have significantly
      lower hit rates than Caucasians when searched for 6/6 antigen matches, but there
      was no significant difference between the three ethnic groups in finding a 5/6
      antigen matched donor. This study supports the policy of the New Zealand Bone
      Marrow Donor Registry in recruiting New Zealand Maori and Pacific Islanders.

PMID- 10084263
TI  - Progressive multifocal leukoencephalopathy after autologous bone marrow
      transplantation and alpha-interferon immunotherapy.
AB  - A patient with a stage IV mantle cell lymphoma (according to the REAL
      classification) was treated with high-dose chemotherapy and autologous bone
      marrow transplantation. One year later while on alpha-interferon immunotherapy
      she suffered from progressive loss of short-term memory and reported difficulties
      in recognizing objects. Magnetic resonance imaging (MRI) showed a vast ring
      enhancing lesion of the left postcentral parietal area. Serial stereotactic
      biopsies disclosed progressive multifocal leukoencephalopathy without JC-virus in
      the cerebrospinal fluid. Therapy with subcutaneous interleukin-2 (IL-2) every
      other day and intrathecal cytarabine once a week was started. After 4 weeks the
      patient refused further treatment. Nevertheless her condition improved over the
      next 8 months and MRI scans showed a marked improvement in the lesions.

PMID- 10084264
TI  - Correction of bone marrow failure in dyskeratosis congenita by bone marrow
      transplantation.
AB  - Dyskeratosis congenita is recognized by its dermal lesions and constitutional
      aplastic anemia in some cases. We report successful allogeneic bone marrow
      transplantation in two siblings with this disease from their sister, and their
      long term follow-up. We used reduced doses of cyclophosphamide and busulfan for
      conditioning instead of total body irradiation. Also, we report late adverse
      effects of transplantation which are not distinguishable from the natural course
      of disease.

PMID- 10084265
TI  - Formation of fibrin clots in cryopreserved stem cell bags during thawing
      procedure: lack of impact on engraftment in autologous stem cell transplantation.

PMID- 10084266
TI  - A single apheresis to achieve a high number of peripheral blood CD34+ cells in a
      lithium-treated patient with acute myeloid leukaemia.

PMID- 10084267
TI  - Contact transscleral diode cyclophotocoagulation for refractory glaucoma.
AB  - PURPOSE: To evaluate the effect of contact transscleral diode
      cyclophotocoagulation on intraocular pressure (IOP), vision, number of
      medications, and complications in a heterogenous population of patients with
      refractory glaucoma. METHODS: Clinical data for all patients undergoing contact
      transscleral diode cyclophotocoagulation for refractory glaucoma at the Medical
      College of Georgia between November 1994 and November 1996 were reviewed. Forty
      seven eyes of forty-seven patients followed for at least one month were included.
      Visual acuity, IOP, number of medications, and complications were noted for
      follow-up periods as long as 24 months. RESULTS: At final follow-up examination
      (range 1-24 months, median 9 months), the average decrease in IOP was 21+/-16
      mmHg. Thirty-one (66%) patients had final IOP between 7 and 21 mmHg. Medications
      were decreased by an average of 1.1. Twenty-six (62%) of 42 patients with vision
      before surgery had stable or improved visual acuity at the final follow-up visit;
      16 (38%) had a deterioration in visual acuity. Neovascular glaucoma was
      associated with a posttreatment IOP less than 7 mmHg. CONCLUSION: Contact
      transscleral diode cyclophotocoagulation is effective in lowering IOP in eyes
      with refractory glaucoma. It also serves to reduce the number of medications
      required for appropriate IOP control. Loss of visual acuity remains an important
      concern. Acute complications tend to be transient. Further study is needed to
      identify patients at risk for markedly reduced IOP after this procedure and for
      modulation of the protocol to decrease such risk.

PMID- 10084268
TI  - Body mass index in glaucoma.
AB  - PURPOSE: To compare body mass index (BMI) of patients with open-angle glaucoma or
      normal-tension glaucoma with BMI in control subjects. METHODS: BMI was calculated
      for 288 control subjects, 42 patients with open-angle glaucoma with treated
      intraocular pressure (IOP) higher than 21 mmHg, 87 patients with open-angle
      glaucoma with progression of glaucomatous damage despite IOP less than 21 mmHg,
      and 57 patients with normal-tension glaucoma. RESULTS: There was no statistical
      difference in BMI between patients with glaucoma and control subjects. If
      anything, there was a tendency for patients with glaucoma to have a lower BMI
      than control subjects. CONCLUSION: These data show that obesity seems not to be a
      risk factor for glaucoma.

PMID- 10084269
TI  - Effects of long-term hypotensive therapy with nonselective beta-blockers on
      ocular hemodynamics in primary open-angle glaucoma.
AB  - PURPOSE: Vascular factors have been implicated in the progression of glaucoma,
      but the impact of long-term beta blocker therapy on ocular circulation remains
      largely undefined. The purpose of this study was to prospectively evaluate the
      level of retrobulbar blood flow in patients with primary open-angle glaucoma
      (POAG) before and during long-term treatment with a nonselective topical beta
      blocker, and to compare these measures with those in untreated control subjects.
      METHODS: Twelve control subjects and 12 patients with POAG were tested for
      intraocular pressure (IOP), heart rate, blood pressure, contrast sensitivity,
      visual field sensitivity, and retrobulbar flow velocity as measured by color
      Doppler imaging (CDI). Patients were evaluated after 4 weeks of drug washout and
      again after 3 and 6 months of treatment with a nonselective beta blocking agent.
      Control subjects were tested once. RESULTS: At baseline, patients with POAG had
      significantly higher IOP than normal controls; CDI measures of the central
      retinal artery (CRA) and short posterior ciliary artery (SPCA) in the patients
      were significantly different from those in control subjects. In the patients,
      treatment resulted in a significant reduction in IOP and in CRA and SPCA
      resistance index. CONCLUSION: Untreated patients with POAG have altered
      circulation in the CRA and SPCA compared with subjects of similar age and gender.
      These measures recover significantly during topical beta blocker therapy. The
      relationship of the pretreatment deficit and posttreatment recovery of CDI blood
      flow measures to the progression and therapeutic impediment of glaucomatous optic
      nerve deterioration remains to be determined.

PMID- 10084270
TI  - Quantification of blood--aqueous barrier breakdown after trabeculectomy:
      pseudoexfoliation versus primary open-angle glaucoma.
AB  - PURPOSE: Impairment of the blood-aqueous barrier in unoperated eyes with
      pseudoexfoliation syndrome has been demonstrated by fluorescein angiography,
      fluorophotometry, measurement of aqueous flare, and determination of aqueous
      protein. We performed noninvasive quantification of aqueous flare using the laser
      flare-cell meter to compare blood-aqueous barrier breakdown after trabeculectomy
      in eyes with primary open-angle glaucoma (POAG) and in eyes with
      pseudoexfoliative glaucoma (PEX). METHODS: Twenty eyes with PEX and 20 eyes with
      POAG were included in the study. Trabeculectomy was performed by two surgeons
      according to a standard trabeculectomy technique. Intra- and postoperative
      treatments were identical in both groups. Aqueous flare was quantitatively
      determined using the laser flare-cell meter FC-1000 (Kowa, Tokyo, Japan) before
      and 3, 5, 7, and 9 days after trabeculectomy. Absolute flare and difference
      between post- and preoperative flare values were statistically analyzed using the
      Mann-Whitney U-Test for independent samples. RESULTS: Before surgery, aqueous
      flare values were significantly higher in PEX than in POAG. On days 3, 5, 7 and 9
      after surgery, flare values were significantly higher in eyes with PEX than in
      eyes with POAG. Absolute differences between post- and preoperative flare values
      also were significantly higher in eyes with PEX, but this was not true for
      percentage values. CONCLUSION: These results show that substantial blood-aqueous
      barrier breakdown occurs in eyes with PEX after trabeculectomy. These alterations
      may contribute to early or late complications of trabeculectomy and indicate the
      need for close postoperative follow-up evaluation in eyes with PEX.

PMID- 10084271
TI  - Intraocular pressure-lowering effects of latanoprost monotherapy versus
      latanoprost or pilocarpine in combination with timolol: a randomized, observer
      masked multicenter study in patients with open-angle glaucoma. Italian
      Latanoprost Study Group.
AB  - PURPOSE: To compare intraocular pressure (IOP) after adding either latanoprost or
      pilocarpine to timolol treatment or switching to latanoprost monotherapy in
      glaucomatous eyes in which IOP was inadequately controlled with timolol. METHODS:
      This 6-month randomized study comprised 148 patients with primary open-angle or
      pseudoexfoliation glaucoma, which was inadequately controlled with topical beta
      adrenergic antagonists. After a 2- to 4-week run-in period with timolol 0.5%
      twice daily, patients were assigned in randomized fashion to three study groups:
      one group received add-on therapy of latanoprost 0.005% once daily, the second
      group received add-on therapy of pilocarpine 2% three times daily, and the third
      group switched to latanoprost 0.005% once daily. Mean diurnal IOP was measured at
      baseline and after 3 and 6 months of treatment. RESULTS: At 6 months, 128
      patients had completed the study. Diurnal IOP was significantly reduced from
      baseline in all groups. Adding latanoprost to timolol treatment reduced diurnal
      IOP by 6.1+/-0.3 mmHg (-28%), adding pilocarpine to timolol treatment reduced
      diurnal IOP by 4.2+/-0.3 mmHg (-19%), and switching from timolol to latanoprost
      monotherapy reduced diurnal IOP by 5.5+/-0.3 mmHg (-25%). CONCLUSION: A
      significantly greater reduction in diurnal IOP was achieved after addition of
      latanoprost than after addition of pilocarpine in patients in whom IOP was not
      adequately controlled with timolol alone. Further, the results of this study
      indicate that a switch to latanoprost monotherapy can be attempted before
      combination treatment is initiated.

PMID- 10084272
TI  - Visible and near-infrared imaging of the nerve fiber layer of the isolated rat
      retina.
AB  - PURPOSE: To develop an isolated rat retina preparation suitable for the study of
      the reflectance of the mammalian retinal nerve fiber layer (RNFL). METHODS: A rat
      retina with a short piece of optic nerve attached was dissected free from the eye
      and stretched over a slit in a black membrane. The retina was placed in a black
      chamber perfused with warmed and oxygenated physiologic solution. Imaging
      microreflectometry was used to acquire images of the RNFL at wavelengths from 400
      to 830 nm and over time. RESULTS: At all wavelengths the isolated retina provided
      high-contrast images of nerve fiber bundles against a uniform, dark background.
      The nerve fiber bundles had a speckled texture, especially at long wavelengths.
      Time-lapse movies showed that over a period of several minutes the speckle
      pattern slowly changed. Although the general appearance of the bundles was
      similar at two closely spaced wavelengths (660 and 680 nm), the detailed patterns
      were completely different. CONCLUSION: The isolated retina preparation is well
      suited to the study of the optical properties of the RNFL. The speckled texture
      of nerve fiber bundles probably results from optical interference in the
      scattered light. The slow change in pattern implies that the size and/or shape of
      the scattering structures must change with time.

PMID- 10084273
TI  - Histomorphometric analysis of optic nerve changes in experimental glaucoma.
AB  - PURPOSE: To assess relative changes in different tissue components of optic nerve
      and their relationship to nerve fiber loss in the experimental monkey model of
      glaucoma. METHODS: Chronic intraocular pressure (IOP) elevation was induced by
      laser trabeculoplasty in the right eye of eight monkeys (Macaca fascicularis).
      Both experimental right optic nerves and control left optic nerves were studied.
      Histomorphometric analysis was performed on optic nerve cross-sections using
      bright field microscopy with camera lucida. Cross-sectional areas of optic nerve
      tissue components were estimated by point counting. Nerve fiber density was
      estimated by unbiased random sampling. Nerve fiber number was calculated by
      multiplying nerve fiber density with neuroglial area. RESULTS: Varying degrees of
      nerve fiber loss were seen in eight optic nerves with chronic IOP elevation. More
      than 50% nerve fiber loss was noted in four of eight experimental optic nerves.
      In these severely affected optic nerves, total optic nerve area was significantly
      decreased compared with control optic nerves. Among the optic nerve tissue
      components, only the ratio of myelinated fiber area to total optic nerve area was
      significantly decreased. The ratio of extraaxonal area to total optic nerve area
      was significantly increased, whereas the ratio of interfascicular septal area to
      total optic nerve area did not change significantly. For all optic nerves,
      differences in nerve fiber count between control and experimental optic nerves
      showed the strongest correlation with differences in myelinated fiber area,
      followed by differences in extraaxonal area and total optic nerve area.
      CONCLUSION: This histomorphometric study suggests the validity of the
      experimental monkey model of glaucoma in studying changes occurring in the
      nonaxonal optic nerve tissue components in human glaucomatous optic neuropathy.
      Glial scar tissue area was significantly increased in optic nerves with severe
      glaucomatous damage. Although a decrease in total optic nerve area was observed,
      among the optic nerve tissue components only myelinated nerve fiber area
      decreased significantly. Myelinated nerve fiber area also showed the strongest
      association with nerve fiber loss in experimental glaucoma.

PMID- 10084274
TI  - Quantification of intraoperative administration of mitomycin-C in filtering
      surgery with surgical sponge material.
AB  - PURPOSE: To determine the absorption and release of mitomycin-C 0.4 and 0.2 mg/mL
      from sponge-like specimens of Spongostan film (Ferrosan, Copenhagen, Denmark) and
      the scleral and conjunctival impregnation in an experimental model of filtering
      surgery. METHODS: The maximum amount of mitomycin per volume unit that Spongostan
      is able to absorb was determined physically as the difference between dry weight
      and soaked weight. Mitomycin-C activity in known volumes of Spongostan after
      mitomycin-C release in vitro also was determined at 0, 1, 10, and 30 seconds and
      1, 3, 5, 10, 15, and 30 minutes. Antibiotic activity of the specimens was
      evaluated by means of bioassay. Millimeters of inhibition of bacterial growth
      were related to microg of mitomycin activity according to a reference curve
      obtained from known amounts of mitomycin-C. Finally, 10 eyes of 10 rabbits
      underwent filtering surgery with intraoperative application of mitomycin by means
      of the Spongostan film. The Spongostan implants then were removed and tested for
      mitomycin activity. Scleral and conjunctival specimens were obtained for
      bioassay. RESULTS: The maximum capacity of 25 mm2 x 0.5 mm thick Spongostan films
      saturated in 0.4 and 0.2 mg/mL solutions of mitomycin-C were 8.49 microg and 4.23
      microg, respectively. Biologic activity (bioassay determination) was 8.24 microg
      and 4.19 microg of mitomycin-C, respectively. In vitro release of mitomycin was
      gradual until 30 minutes. In vivo mitomycin release from Spongostan after 5
      minutes was 6.91 microg. Impregnation with the antimitotic was better in
      conjunctiva than sclera. CONCLUSION: Bioassay permits quantification of mitomycin
      C activity. The release from sponge specimens is gradual, and impregnation was
      better in conjunctiva than sclera.

PMID- 10084275
TI  - The relationship between gelatinase A activity in aqueous humor and glaucoma.
AB  - PURPOSE: To investigate whether abnormal expression of gelatinase A in aqueous
      humor may be related to the development of glaucoma, the activity of gelatinase A
      in aqueous humor of patients with glaucoma and patients with cataract was
      measured and compared. METHODS: Six primary patients with open-angle glaucoma
      (POAG), four patients with chronic angle closure glaucoma (CACG), four patients
      with normal tension glaucoma (NTG), and 14 patients with cataract were enrolled.
      The aqueous humor of each patient was collected during surgery, and total protein
      concentration and gelatinase activity in the aqueous humor were measured by
      protein assay kit and zymography, respectively. RESULTS: In patients with POAG,
      total protein concentration doubled and gelatinase A activity increased by 3.9
      times compared with patients with cataract. However, there were no statistically
      significant differences in total protein concentration and gelatinase A activity
      in patients with CACG or NTG compared with patients with cataract. CONCLUSION:
      The development of POAG may be associated with the abnormal expression of
      gelatinase A in aqueous humor.

PMID- 10084276
TI  - Morphologic changes in chronic high-pressure experimental glaucoma in rhesus
      monkeys.
AB  - PURPOSE: To investigate morphologic changes in the posterior segment of the eye
      and optic nerve head (ONH) in rhesus monkeys with experimental glaucoma, and to
      evaluate the effect of age and vascular disease on the glaucomatous damage.
      METHODS: This study was conducted in 36 eyes of rhesus monkeys 11 to 24 years of
      age. Experimental glaucoma was produced by laser photocoagulation of the anterior
      chamber angle in 28 eyes, and the remaining 8 eyes served as the nonglaucomatous
      group. Of the 28 glaucomatous eyes, 19 belonged to animals with experimental
      atherosclerosis and chronic arterial hypertension (A-H group); the remaining 9
      had no A-H (non-AH group). Among the 8 eyes without glaucoma, 5 belonged to A-H
      animals and the remaining 3 to animals without A-H. All eyes underwent IOP
      measurements and fundus photography before laser photocoagulation and serially
      thereafter for 4 to 60 months (median 22.5 months). After enucleation, eyes were
      fixed in formalin for light microscopic studies. Morphologic abnormalities were
      evaluated and graded. Correlation analyses between morphologic parameters and
      clinical data were performed. RESULTS: The highest IOP ranged from 44 to 80 mmHg,
      but during the follow-up period median IOP was mostly 28 mmHg (mean 27+/-4.8
      mmHg). On histopathologic examination, the eyes showed moderate to severe atrophy
      of the temporal peripapillary choroid (67%), choriocapillaris (70%), and RPE
      (12%); axonal atrophy in the retinal nerve fiber layer (85%), prelaminar region
      (69%), lamina cribrosa (66%), and retrolaminar region (82%); fibrous septal
      thickening in the lamina cribrosa (77%) and retrolaminar region (86%); bowing
      backward of the lamina cribrosa (77%); overall tissue atrophy in the prelaminar
      region (81%); and retinal ganglion cell atrophy (74%). The data showed a positive
      correlation between the ONH damage and atrophic changes in the temporal
      peripapillary choroid, and suggested greater damage in animals with A-H than in
      those without A-H. CONCLUSION: Vascular disease may influence glaucomatous damage
      in the ONH, as damage in the ONH was greater in animals with A-H than in those
      without A-H. A similar relationship also may exist between age and glaucomatous
      damage, but this needs to be investigated further in a larger study. It is
      postulated that the bowing back of the lamina cribrosa seen in optic disc cupping
      is produced by retrolaminar septal fibrosis and axonal loss. Although elevated
      IOP no doubt played an important role, the data suggest that the glaucomatous
      changes that were observed in this study are not simply mechanical in nature (due
      to the raised IOP), but may represent a multifactorial phenomenon.

PMID- 10084277
TI  - The effect of latanoprost and brimonidine on rabbit subconjunctival fibroblasts.
AB  - PURPOSE: Subconjunctival fibroblasts play a critical role in scarring and
      treatment failure in fistulizing surgery for glaucoma. The proliferation of
      subconjunctival fibroblasts appears to be modulated by topical glaucoma
      medications. This study was conducted to evaluate the effects of latanoprost and
      brimonidine on subconjunctival fibroblast proliferation in rabbit eyes. METHODS:
      Twelve pigmented Dutch-belted rabbits were divided into treatment groups of four:
      latanoprost 0.005%, brimonidine 0.2%, or balanced saline solution (BSS) each were
      administered to one treatment group, both eyes of each rabbit, twice a day, 6
      days a week for 10 weeks. The eyes were then enucleated along with the
      conjunctiva, fixed, processed, and evaluated by light microscopy and
      immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) and
      anti-muscle-specific actin antibody (HHF-35). Fibroblast cell counts were
      performed at magnification x40. RESULTS: In all groups, few inflammatory cells
      were seen in the subconjunctival space under light microscopy. PCNA staining
      revealed a statistically significant increase in the mean number of labeled
      fibroblasts in the group receiving brimonidine compared with the control (BSS)
      group. The group receiving latanoprost also had a significantly higher mean
      number of labeled fibroblasts than the groups receiving brimonidine or BSS. Only
      a few fibroblasts stained positively with the anti HHF antibody. Eyes treated
      with latanoprost, however, had significantly higher numbers of positively labeled
      cells than eyes treated with brimonidine or BSS. CONCLUSION: When applied to
      rabbit eyes, latanoprost and brimonidine appear to increase the number of
      positively labeled proliferating subconjunctival fibroblasts.

PMID- 10084278
TI  - Neural networks for visual field analysis: how do they compare with other
      algorithms?
AB  - PURPOSE: To compare the performance of a neural network in identifying visual
      field defects with the performance of other available algorithms. METHODS: A feed
      forward neural network with a single hidden layer was trained to recognize visual
      field defects previously collected in a longitudinal follow-up glaucoma study,
      and then tested on fields taken from the same study but not used in the training.
      The receiver operating characteristics of the network then were compared with the
      previously determined performance of other algorithms on the same data set.
      RESULTS: At a specificity greater than 90%, the neural network was more sensitive
      than any of the available algorithms (although only the global indices were
      available for comparison, as the cluster and cross-meridional algorithms did not
      achieve such high specificity at their current settings). At a lower specificity
      (80-85%), the neural network was unable to attain the high sensitivity of the
      cluster or cross-meridional algorithms; in fact, the cluster algorithm from the
      Low-Tension Glaucoma study was significantly more sensitive. CONCLUSION: The
      receiver operating characteristics of a feed-forward neural network designed to
      detect visual field defects were explored. At a very high specificity (90-95%) a
      neural network performed better than the global indices. However, at a lower
      specificity (78%-88%), the neural network performed worse than cluster and cross
      meridional algorithms.

PMID- 10084279
TI  - Management of congenital glaucoma.

PMID- 10084280
TI  - Cellular iron metabolism.
AB  - Iron is essential for oxidation-reduction catalysis and bioenergetics, but unless
      appropriately shielded, iron plays a key role in the formation of toxic oxygen
      radicals that can attack all biological molecules. Hence, specialized molecules
      for the acquisition, transport (transferrin), and storage (ferritin) of iron in a
      soluble nontoxic form have evolved. Delivery of iron to most cells, probably
      including those of the kidney, occurs following the binding of transferrin to
      transferrin receptors on the cell membrane. The transferrin-receptor complexes
      are then internalized by endocytosis, and iron is released from transferrin by a
      process involving endosomal acidification. Cellular iron storage and uptake are
      coordinately regulated post-transcriptionally by cytoplasmic factors, iron
      regulatory proteins 1 and 2 (IRP-1 and IRP-2). Under conditions of limited iron
      supply, IRP binding to iron-responsive elements (present in 5' untranslated
      region of ferritin mRNA and 3' untranslated region of transferrin receptor mRNA)
      blocks ferritin mRNA translation and stabilizes transferrin receptor mRNA. The
      opposite scenario develops when iron in the transit pool is plentiful. Moreover,
      IRP activities/levels can be affected by various forms of "oxidative stress" and
      nitric oxide. The kidney also requires iron for metabolic processes, and it is
      likely that iron deficiency or excess can cause disturbed function of kidney
      cells. Transferrin receptors are not evenly distributed throughout the kidney,
      and there is a cortical-to-medullary gradient in heme biosynthesis, with greatest
      activity in the cortex and least in the medulla. This suggests that there are
      unique iron/heme metabolism features in some kidney cells, but the specific
      aspects of iron and heme metabolism in the kidney are yet to be explained.

PMID- 10084281
TI  - Iron and anemia of chronic disease.
AB  - Anemia of chronic disease (ACD) is the most frequent anemia found in hospitalized
      patients, often occurring in subjects suffering from chronic inflammatory
      disorders. The underlying diversion of iron traffic leads to a withdrawal of the
      metal from the sites of erythropoiesis and the circulation to the storage
      compartment in the reticuloendothelial system, thus resulting, at the same time,
      in hypoferremia and hyperferritinemia. Proinflammatory and antiinflammatory
      cytokines, acute-phase proteins, and radicals are prominently involved in causing
      these disturbances of iron homeostasis. The role of these factors, as well as the
      pathophysiological reasons for the development of ACD, is discussed in this
      review.

PMID- 10084282
TI  - Iron deficiency in patients with renal failure.
AB  - The anemia of renal failure is caused by the lack of sufficient quantities of
      endogenous erythropoietin. With the availability of recombinant human
      erythropoietin (rHuEPO), however, it has become apparent that to achieve a given
      target, hematocrit requires proper management of iron replacement, as well as the
      administration of rHuEPO. Iron deficiency, either absolute or functional, will
      occur in most, if not all, patients on hemodialysis receiving rHuEPO because of
      the increased demand for iron driven by the accelerated erythropoiesis that
      occurs with exogenous rHuEPO administration, coupled with ongoing blood losses
      from dialyzer and tubing, blood sampling, gastrointestinal blood loss, and blood
      losses at the time of dialysis needle placement and removal. Blood loss is less
      of a problem in patients on peritoneal dialysis, but poor iron intake and
      increased demand for iron are also seen, the latter in patients receiving rHuEPO.
      It is essential, therefore, for renal health professionals to understand iron
      metabolism in dialysis patients in order to properly balance the therapy of renal
      anemia with rHuEPO and supplemental iron.

PMID- 10084283
TI  - Inherited disorders of iron metabolism.
AB  - Recent molecular studies have resulted in the identification of genetic
      alterations underlying hereditary disorders of iron metabolism. One example is
      the discovery of the HFE gene that is mutated in patients suffering from
      hereditary hemochromatosis. This autosomal recessive disorder has an estimated
      carrier frequency that varies between 0.07 and 0.13, thus representing one of the
      most common genetically determined metabolic disorders. The identification of the
      hemochromatosis mutations has encouraged efforts to investigate other conditions
      with iron overload for a putative interaction with these genetic variants. Few
      data are already available suggesting, for example, that iron overload in
      patients with sporadic porphyria cutanea tarda is associated with mutations in
      the hereditary hemochromatosis gene. However, it is obvious that disorders of
      iron metabolism have a multifactorial pathogenesis, including environmental and
      genetic factors. Thus, many questions remain to be answered about whether a
      genetic predisposition exists for development of various iron-loading or iron
      deficiency phenotypes. This review focuses on the most recent advances in the
      field of hereditary disorders of iron metabolism and discusses their potential
      implications for nephrologists.

PMID- 10084284
TI  - Iron overload in renal failure patients: changes since the introduction of
      erythropoietin therapy.
AB  - Iron overload was a common complication in patients with chronic renal failure
      treated with dialysis prior to the availability of recombinant human
      erythropoietin (rHuEPO) therapy. Iron overload was the result of
      hypoproliferative erythroid marrow function coupled with the need for frequent
      red blood cell transfusions to manage symptomatic anemia. The repetitive use of
      intravenous iron with or without the use of red blood cell transfusions also
      contributed to iron loading and was associated with iron deposition in liver
      parenchymal and reticuloendothelial cells; however, there were no abnormal liver
      function tests or evidence of cirrhosis unless viral hepatitis resulted from the
      transfusions. With rHuEPO therapy, the excess iron stores were shifted back into
      circulating red blood cells as the anemia was partially corrected, and red blood
      cells were lost from circulation by the hemodialysis procedure. After several
      years of rHuEPO therapy, most hemodialysis patients required iron supplements to
      replace the continuing blood losses related to hemodialysis. The potential
      complications of iron overload (parenchymal iron deposition, permanent organ
      damage, increased risk of bacterial infections, and increased free radical
      generation) are reviewed in the context of this setting.

PMID- 10084285
TI  - Hypochromic red blood cells and reticulocytes.
AB  - The management of recombinant human erythropoietin (rHuEPO) treatment in
      hemodialysis patients requires close monitoring of iron status, because the
      pharmacologically stimulated erythropoiesis is particularly dependent on a
      continuous supply of iron. Parameters commonly measured to assess iron status are
      serum ferritin and the transferrin saturation. Both are indirect measures of iron
      availability for hemoglobin synthesis and frequently do not permit an assessment
      of the adequacy of iron supply to the erythron. Using flow cytometry, cell volume
      and hemoglobin concentration can be measured in individual red blood cells and
      reticulocytes. Based on these techniques, two parameters have proved to be
      particularly useful in identifying iron-deficient erythropoiesis. (a) The
      percentage of hypochromic erythrocytes (defined as red blood cells with a
      hemoglobin concentration of less than 28 g/dl) has been shown to detect
      insufficient marrow iron supply with a fairly good accuracy. (b) More recently,
      determination of the content of hemoglobin in reticulocytes (CHr) has been
      suggested by a number of authors to be even more sensitive in detecting iron
      deficient erythropoiesis. For those who have access to an H*3 hematology
      analyzer, both indices can be determined at the time of a routine blood count at
      a minimal incremental cost.

PMID- 10084286
TI  - Erythropoietin and iron.
AB  - Serum ferritin concentration is most informative in estimating the amount of
      storage iron available for a particular individual. The serum transferrin
      receptor concentration, in contrast to serum ferritin, provides direct
      information about any deficit in the adequacy of iron supply to the
      erythropoiesis. The combination of serum transferrin receptor and serum ferritin
      provides complete information about storage and functional iron compartments.
      Using this combination along with the hemoglobin concentration, it is possible to
      define the iron nutritional status completely. Inflammatory conditions as well as
      parenteral iron administration interfere, however, with the direct and
      quantitative ferritin to storage iron relationship and, therefore, have to be
      considered carefully with respect to diagnostic purposes. The diagnostic use of
      the serum transferrin receptor is presently limited because of limitations in
      methodology and definition (standardization) of reference ranges.

PMID- 10084287
TI  - Erythrocyte zinc protoporphyrin.
AB  - In iron deficiency and lead poisoning, the enzyme ferrochelatase catalyzes the
      incorporation of zinc, instead of iron, into protoporphyrin IX, resulting in the
      formation of zinc protoporphyrin (ZPP). In healthy blood donors, there is a good
      inverse correlation between serum ferritin and ZPP levels. In renal failure
      patients and in patients with anemia caused by a variety of chronic disorders,
      two different types of iron deficiency are found: (a) absolute iron deficiency
      and (b) relative, or functional, iron deficiency. The latter occurs when iron,
      despite adequate stores, is not delivered rapidly enough to the erythroblasts.
      ZPP is not only indicative of absolute iron deficiency, but it is also, for now,
      the best indicator of iron-deficient erythropoiesis, along with the percentage of
      hypochromic red blood cells. By contrast, serum ferritin and transferrin
      saturation may not adequately assess functional iron deficiency. Elevated ZPP
      levels in renal failure patients can be caused by different pathogenetic
      mechanisms, such as chronic inflammatory disease, lead poisoning, and the
      presence of uremic factors, all of which could potentially inhibit heme
      biosynthesis. However, ZPP levels do not consistently predict an erythropoietic
      response to iron supplementation in maintenance hemodialysis patients, and thus,
      iron overload during i.v. iron supplementation cannot be detected by measuring
      ZPP.

PMID- 10084288
TI  - Strategies for iron supplementation: oral versus intravenous.
AB  - Iron supplementation has become an integral part of the management of patients
      receiving epoetin therapy, and clinicians have found it necessary to learn how
      and when to use it to the best advantage. Three routes of administration for iron
      are available: oral, intramuscular, and intravenous. Oral iron has the advantage
      of being simple and cheap, but it is limited by side-effects, poor compliance,
      poor absorption, and low efficacy. Intravenous iron is the best means of
      guaranteeing delivery of readily available iron to the bone marrow, but it
      requires greater clinical supervision. The i.v. iron preparations vary widely in
      their degradation kinetics, bioavailability, side-effect profiles, and maximum
      dose for single administration. Iron dextran is hampered by a small but
      significant risk of anaphylaxis, whereas all i.v. iron preparations can induce
      "free iron" reactions if the circulating plasma transferrin is overloaded.
      Intravenous iron may be given in advance of epoetin therapy, as concomitant
      treatment to prevent the development of iron deficiency, as treatment of absolute
      or functional iron deficiency, or as adjuvant therapy to enhance the response to
      epoetin in iron-replete patients. Markers of iron status that may indicate a need
      for i.v. iron include a serum ferritin of less than 100 microg/liter, a
      transferrin saturation of less than 20%, and a percentage of hypochromic red
      cells more than 10%. Various regimens are available for giving i.v. iron: low
      dose administration of 20 to 60 mg every dialysis session in hemodialysis
      patients, medium-dose administration of 100 to 400 mg, and high-dose
      administration of 500 to 1000 mg. Iron sodium gluconate can only be given as a
      low-dose regimen because of toxicity, whereas the only preparation suitable for
      high-dose administration is iron dextran. Although concerns have been raised
      regarding iron overload and long-term toxicity with i.v. iron therapy in terms of
      increased risk of infections, cardiovascular disease, and malignancy, there is
      little evidence to substantiate this in patients receiving epoetin. Care should
      be taken, however, to prevent the serum ferritin rising above 800 to 1000
      microg/liter and the transferrin saturation above 50%. Provided this is done, the
      benefits of i.v. iron almost certainly outweigh the risks in terms of optimizing
      the response to epoetin therapy.

PMID- 10084289
TI  - Beneficial effects of iron therapy in renal failure patients on hemodialysis.
AB  - Iron deficiency is a common problem in patients treated with hemodialysis. If not
      detected and treated appropriately, the effectiveness of recombinant human
      erythropoietin therapy is compromised. Much has been learned in recent years with
      respect to iron therapy for hemodialysis patients. A series of studies have
      clearly defined the efficacy of intravenous iron compounds, and recently released
      clinical practice guidelines have set the appropriate clinical context for the
      use of these agents. The purpose of this article is to examine the beneficial
      effects of iron replacement therapy for hemodialysis patients.

PMID- 10084290
TI  - Iron status and iron supplementation in peritoneal dialysis patients.
AB  - Iron deficiency represents an important problem in peritoneal dialysis patients,
      especially during erythropoietin therapy. A combination of serum ferritin,
      transferrin saturation, and/or the percentage of hypochromic red cells should be
      used to assess iron status in peritoneal dialysis patients. Primarily, oral iron
      supplementation should be the preferred therapy. However, most of the studies
      using oral substitution in erythropoietin-treated peritoneal dialysis patients
      show a progressive decline of serum ferritin. Therefore, parenteral iron
      supplementation is required in part of the patients, and the intravenous route
      should be preferred in these cases. Intravenous iron therapy is recommended if
      serum ferritin falls below 100 microg/liter and should be stopped if the serum
      ferritin level is more than 650 microg/liter. The optimal form of intravenous
      iron supplementation is still unclear. Injections once to three times per week
      restrict the patients' flexibility, but application of higher doses in longer
      intervals may lead to an impairment of neutrophil functions, probably connected
      to a higher risk of infection. We treated 17 stable peritoneal dialysis patients
      with 100 or 200 mg iron saccharate monthly over a period of six months and found
      an increase of transferrin saturation (from 12.1+/-1.6 to 20.9+/-2.4%, P =
      0.026), serum ferritin (from 100.4+/-32.0 to 372.4+/-54.6 microg/liter, NS) and
      hematocrit (from 32.0+/-0.8% to 35.1+/-0.9%, P = 0.099). The required
      erythropoietin dosage could be reduced significantly (from 148.4+/-30.3 to 69.4+/
      19.5 U/kg/week, P = 0.025). Side effects occurred in 0.9% after application of
      100 mg and in 5.9% after injection of 200 mg iron saccharate. The incidence of
      catheter infections and peritonitis was the same in the period before and after
      the start of treatment. Further studies are needed to find the most suitable
      regime of iron supplementation for peritoneal dialysis patients.

PMID- 10084291
TI  - Intravenous iron for the treatment of predialysis anemia.
AB  - This article, based on our own studies and those of others, presents evidence to
      show that the anemia of chronic renal failure in the predialysis period is, to a
      significant extent, caused by iron deficiency and can be improved in most cases
      by the administration of intravenous (i.v.) but not oral iron. We estimate that
      in approximately 30% of all predialysis patients with anemia, a target hematocrit
      (Hct) of 35% can be reached and maintained by giving i.v. iron alone without
      exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the
      percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin
      (EPO-usually in only low doses-is added, the combination has an additive effect
      on the Hct response, and almost all anemic predialysis patients can reach and
      maintain the target Hct of 35% over a one-year period. Therefore, the advantage
      of maintaining adequate iron stores with i.v. iron is that if EPO is needed,
      lower doses will be required to achieve the target Hct than if EPO were used
      alone. This not only avoids the high cost of EPO therapy but also its associated
      side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose
      complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in
      over 20,000 infusions over a four-year period in 360 hemodialysis, 123
      predialysis, and 58 peritoneal dialysis patients.

PMID- 10084292
TI  - Erythropoietin and renal transplantation.
AB  - The advent of erythropoietin (rHuEPO) has revolutionized the treatment of anemia
      in end-stage renal disease. While many studies indicate beneficial effects of
      rHuEPO in hemodialysis, peritoneal dialysis and predialysis patients, the impact
      of the drug in renal transplantation is less clear. Treatment with rHuEPO may
      reduce the degree of allosensitization produced by random blood transfusion while
      still allowing the possibility of the transplant survival benefit derived from
      deliberate transfusion. Recovery from anemia post-transplantation is hastened by
      treatment with rHuEPO, while patients with failing allografts respond to rHuEPO
      in a fashion similar to dialysis patients, despite the concomitant use of
      immunosuppressives. The erythropoietic response to rHuEPO is abrogated during
      episodes of acute rejection, and restored when successful treatment of rejection
      has occurred. Iron therapy is a critical factor for support of erythropoiesis and
      prevention of absolute iron deficiency posttransplantation. In patients
      presenting for renal transplant, the balance of evidence suggests that there is
      no increase in the rate of delayed graft function, graft loss or vascular
      thrombosis for patients who had received prior rHuEPO therapy.

PMID- 10084293
TI  - Anemia and carnitine supplementation in hemodialyzed patients.
AB  - Carnitine supplementation in hemodialyzed patients was studied in a double
      blinded, randomized, controlled trial in order to elucidate the effect of
      intravenous carnitine on renal anemia in patients treated with recombinant human
      erythropoietin (rHuEPO). Twenty stable hemodialysis (HD) patients received
      intravenous L-carnitine after each dialysis session in a dosage of 5 (N = 15) and
      25 (N = 5) mg/kg, respectively, together with intravenous iron saccharate (20
      mg/HD session) for four months and without iron for a further four months. Twenty
      patients received placebo instead of carnitine with an identical iron regimen.
      After a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO
      dose was adjusted monthly when necessary to maintain target hemoglobin levels. At
      study entry (T0), plasma and red blood cell carnitine levels did not correlate
      significantly with the rHuEPO requirement. However, plasma free and total
      carnitine levels showed a significant negative correlation with erythrocyte
      survival time at T0. After four months of coadministration of intravenous iron
      and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD
      patients. In these responders, the weekly rHuEPO dose was decreased significantly
      by 36.9+/-23.3% (183.7+/-131.7 at T0 vs. 126.6+/-127.9 U/kg/week at T4, P <
      0.001). The rHuEPO requirement, however, was unchanged when all carnitine-treated
      patients were compared between T0 and T4 (T0: 172.0+/-118.0 vs. T4: 152.3+/-118.8
      U/kg/week, P = 0.07, NS), but the erythropoietin resistance index decreased
      significantly in this group (T0: 16.0+/-11.0 vs. T4: 13.6+/-10.5 U/kg/week/g of
      hemoglobin, P < 0.02). The erythrocyte survival time was measured in five HD
      patients treated with iron and carnitine at T0 and T4. Two out of these patients
      were carnitine responders and showed an increase of erythrocyte survival time of
      15 and 20%, respectively. After the withdrawal of iron supplementation, the
      rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated
      patients during four more months. According to our data, L-carnitine, in addition
      to iron supplementation, may have an effect on erythropoietin resistance and
      erythrocyte survival time in HD patients. More than half of our patients,
      however, showed no benefit. Further studies to identify those HD patients who
      might have a benefit of carnitine supplementation, as well as studies concerning
      the optimal dosage, duration, and way of administration of carnitine
      supplementation and its mechanism of action, are required.

PMID- 10084294
TI  - Erythropoietin hyporesponsiveness: from iron deficiency to iron overload.
AB  - Iron deficiency is the most frequently encountered cause of suboptimal response
      to recombinant human erythropoietin (rHuEPO). Carefully assessing iron status is
      of paramount importance in chronic renal failure patients prior to or during
      rHuEPO therapy. Because there is great need for iron in the EPO-stimulated
      erythroid progenitors, it is essential that serum ferritin and transferrin
      saturation levels should be maintained over 300 microg/liter and 30%,
      respectively. Investigators have shown that oral iron is unlikely to keep pace
      with the iron demand for an optimal rHuEPO response in uremics. Therefore,
      patients with iron deficiency will always require intravenous iron therapy. The
      early and prompt iron supplementation can lead to reductions in rHuEPO dose and
      hence cost. After the iron deficiency has been corrected or excluded, we must
      remember all of the possible causes of hyporesponsiveness in every rHuEPO-treated
      patient. As dose requirements vary, it is not clear which dose of rHuEPO causes
      this hyporesponsiveness. However, if the patient with iron repletion does not
      respond well after the induction period, the major causes blunting the response
      to rHuEPO should be investigated. Most factors are reversible and remediable,
      except resistant anemia associated with hemoglobinopathy or bone marrow fibrosis,
      which requires a further increase in the rHuEPO dose. By means of early detection
      and correction of the possible causes, the goal of increasing therapeutic
      efficacy can be achieved. Iron overload may lead to an enhanced risk for
      infection, cardiovascular complication, and cancer. Over-treatment with iron
      should be avoided in dialysis patients, despite the fact that the safe upper
      limit of serum ferritin to avoid iron overload is not clearly defined. On the
      other hand, functional iron deficiency may develop even when serum ferritin
      levels are increased. Controversy remains as to whether intravenous iron therapy
      can overcome this form of hyporesponsiveness in iron-overloaded patients.
      Moreover, a treatment option of iron supplementation is not warranted in these
      patients, as the potential hazards of iron overload will be worsened. We
      demonstrated that the mean hematocrit significantly increased from 25.1+/-0.9% to
      31+/-1.2% after eight weeks of intravenous ascorbate therapy (300 mg three times
      a week) in 12 hemodialysis patients with serum ferritin levels of more than 500
      microg/liter. The enhanced erythropoiesis paralleled with a rise in transferrin
      saturation (27.8+/-2.5% vs. 44.8+/-9.5%, P < 0.05) and reductions in erythrocyte
      zinc protoporphyrin (130+/-32 vs. 72+/-19 micromol/mol heme, P < 0.05) and
      monthly rHuEPO dose (24.2+/-4.5 vs. 16.8+/-3.4 x 10(3) units, P < 0.05) at the
      end of study. It is speculated that ascorbate supplementation not only
      facilitates the iron release from storage sites and its delivery to hematopoietic
      tissues, but also increases iron utilization in erythroid cells. Our study
      provides a more complete understanding of the pathogenesis of iron overload
      related anemia and the development of an adjuvant therapy, intravenous ascorbic
      acid, to the existing treatments.

PMID- 10084295
TI  - Toxicity of parenteral iron dextran therapy.
AB  - Parenteral iron dextran is efficacious and safe for iron repletion in patients
      with iron-deficiency anemia. The risk for developing reactions to parenteral iron
      infusion can be attenuated if patients are carefully selected. Patients with
      underlying autoimmune disease, malnutrition with indolent infection, and risk for
      iron overload syndromes should be carefully monitored for complications. Further,
      the rate of infusion and the route of administration of iron dextran play roles
      in the risk of adverse reactions. The purpose of this review is to identify and
      elucidate the mechanisms of the acute and chronic toxicities associated with
      parenteral iron dextran use.

PMID- 10084296
TI  - Iron and infection.
AB  - Intravenous iron therapy maintains iron stores and decreases erythropoietin
      demand in patients undergoing regular dialysis therapy. Microbiology studies show
      a close relationship between the availability of iron and bacterial virulence.
      Iron is also an essential requirement of bacteria for multiplication in the host.
      Therefore, clinical conditions associated with iron excess in the host may
      increase the risk for infection. Parenteral iron has already been shown in human
      and animal studies to be harmful when administered during infection. There is now
      convincing evidence that hydroxyl radicals, produced either by the Fenton
      reaction or by the iron-catalyzed Haber-Weiss reaction, are species responsible
      for the damaging effects of iron. The unavailability of iron limits microbial
      growth but also impairs host resistance. In end-stage renal disease, patients'
      overtreatment with iron enhances the pre-existing risk for infectious
      complications caused by dialysis procedure per se, malnutrition, increased
      intracellular calcium, as well as low and high molecular weight uremic toxins.
      Intravenous iron therapy may not only adversely affect phagocytes in end-stage
      renal disease patients, but also T and B lymphocytes.

PMID- 10084297
TI  - Iron therapy and cancer.
AB  - Anemia in cancer patients has many etiologies. Iron therapy clearly is indicated
      in patients whose anemias are associated with iron deficiency. However, a
      frequent cause of anemia in cancer is the "anemia of chronic disorders," in
      which, although functional iron may be low, tissue iron remains normal or high.
      Administration of iron with erythropoietin to such patients requires careful and
      frequent evaluation of hematologic and iron values. Inadvertent iron loading can
      contribute to deterioration of a variety of organ systems, as well as to
      increased proliferation of neoplastic cells.

PMID- 10084298
TI  - Iron therapy and cardiovascular disease.
AB  - Intensive iron therapy is now a generally accepted adjunct for the treatment of
      renal anemia with recombinant human erythropoietin. However, with the emerging
      role of iron in cardiovascular disease, carcinogenesis, infectious diseases, and
      other disorders, it is no longer appropriate to assume that any amount of stored
      iron is safe until proven otherwise. In this article, the history and current
      status of the "iron hypothesis" on ischemic heart disease are briefly reviewed,
      followed by comments on iron management practices for renal patients.

PMID- 10084299
TI  - A susceptibility locus for epidermodysplasia verruciformis, an abnormal
      predisposition to infection with the oncogenic human papillomavirus type 5, maps
      to chromosome 17qter in a region containing a psoriasis locus.
AB  - Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by an
      abnormal susceptibility to infection with a specific group of related human
      papillomavirus (HPV) genotypes, including the oncogenic HPV5 associated with the
      skin carcinomas developing in about half of EV patients. EV is usually considered
      as an autosomal recessive condition. Taking EV as a model to identify a locus
      underlying the susceptibility to HPV infections, we performed a genome-wide
      search for linkage with 255 microsatellite genetic markers in three
      consanguineous EV families comprising six patients, using the homozygosity
      mapping approach. Homozygosity restricted to affected individuals was observed
      for a marker of chromosome 17q (D17S784) in two families and a marker about 17
      centiMorgan (cM) distal (D17S1807) in the third family. Ten additional
      microsatellite markers spanning 29 cM in this region were analyzed. Two-point lod
      score values greater than 3 were obtained for four markers and multipoint linkage
      analysis yielded a maximum lod score of 10.17 between markers D17S939 and
      D17S802. Recombination events observed in two families allowed a candidate region
      for the EV susceptibility locus to be mapped to the 1 cM region defined by these
      two markers. The EV locus (named EV1) is included in the 17qter region recently
      found to contain a dominant locus for the susceptibility to familial psoriasis.
      It has been shown that patients suffering from psoriasis are likely to constitute
      the reservoir of HPV5. It is thus tempting to speculate that distinct defects
      affecting the same gene may be involved in the two skin conditions.

PMID- 10084300
TI  - Ultrastructural changes in PAM cells after photodynamic treatment with delta
      aminolevulinic acid-induced porphyrins or photosan.
AB  - Photodynamic therapy (PDT) is the combination of a photosensitizing drug (Ps)
      with light in the presence of oxygen leading to the generation of reactive
      molecular species and destruction of cancer cells. In this study we compared PDT
      with two Ps, the hematoporphyrin derivative Photosan (Ph) and delta
      aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX, with respect to
      mitochondrial function and ultrastructural alterations. The effects of PDT were
      investigated in PAM 212 cells after different Ps incubation times, light doses,
      and post-treatment periods. Both Ps induced a light dose-dependent impairment of
      the mitochondrial function with the dose-response curve being steep for ALA and
      flat for Ph. The prolongation of the incubation time from 4 to 20 h resulted in
      an increased reduction of mitochondrial activity after ALA PDT but not after Ph
      PDT. Treatment with an irradiation dose that decreased mitochondrial activity by
      50% (IC50) led to early and profound changes of mitochondrial morphology in ALA
      photosensitized cells, whereas photosensitization with Ph resulted in more
      pronounced alterations of lysosomes. We conclude that at bioequivalent sublethal
      PDT exposures of PAM 212 cells, ALA-induced damage is primarily restricted to
      mitochondria, whereas Ph-induced cytotoxicity is mediated by damage of the
      lysosomal system.

PMID- 10084301
TI  - Topical all-trans retinoic acid augments ultraviolet radiation-induced increases
      in activated melanocyte numbers in mice.
AB  - We have previously shown that daily application of 0.05% retinoic acid to the
      backs of lightly pigmented, hairless HRA:Skh-2 mice increases melanogenesis
      resulting from exposure to solar-simulated ultraviolet radiation. In this study
      we show that as early as 1 wk following commencement of treatment, there is a 2-
      fold increase in the number of epidermal 3,4-dihydroxyphenylalanine positive
      melanocytes in retinoic acid and ultraviolet radiation treated HRA:Skh-2 mice
      compared with mice that received ultraviolet radiation only. This increased to a
      2.9-fold difference by 6 wk. Retinoic acid also augmented ultraviolet radiation
      stimulated melanogenesis, with a 4-fold increase being observed after only 2 wk.
      These findings were also seen in C57BL mice. Ultraviolet radiation and retinoic
      acid needed to be applied to the same skin site for the augmentation in
      melanocyte activation to occur. Ultraviolet B rather than ultraviolet A was
      mainly responsible for melanogenesis and the retinoic acid primarily increased
      ultraviolet B-induced melanogenesis. Furthermore, retinoic acid on it's own, in
      the absence of ultraviolet radiation caused a small but statistically significant
      increase in 3,4-dihydroxyphenylalanine positive melanocyte numbers and
      melanogenesis. Thus topical retinoic acid is a potent modulator of melanocyte
      activation. Alone it is able to increase the number of activated epidermal
      melanocytes and make melanocytes more sensitive to activation by ultraviolet B.

PMID- 10084302
TI  - Oxidative stress can activate the epidermal platelet-activating factor receptor.
AB  - Platelet-activating factor (1-alkyl-2-acetyl-glycero-phosphocholine) is a lipid
      mediator that has been implicated in keratinocyte function and cutaneous
      inflammation. Keratinocytes both synthesize platelet-activating factor and
      express functional platelet-activating factor receptors linked to calcium
      mobilization. Oxidative stress to various cells including keratinocytes can also
      result in the mobilization of intracellular Ca2+, a known stimulus for platelet
      activating factor biosynthesis. The ability of the epidermal platelet-activating
      factor receptors to modulate oxidant-induced signaling was investigated using a
      unique model system created by retroviral-mediated transduction of the platelet
      activating factor receptor-negative epithelial cell line KB with the platelet
      activating factor receptor. Treatment of KB cells with the lipid pro-oxidant tert
      butyl hydroperoxide induced transient increases in intracellular Ca2+ in a
      concentration-dependent fashion. Expression of the platelet-activating factor
      receptor in KB cells lowered the threshold for tert-butyl hydroperoxide-induced
      Ca2+ flux by an order of magnitude (10 microM in control KB versus 1 microM in KB
      cells expressing the platelet-activating factor receptors) and increased the peak
      change in intracellular Ca2+ concentration in response to this lipid
      hydroperoxide. This augmentation of tert-butyl hydroperoxide-induced Ca2+
      mobilization was inhibited by pretreatment with the two competitive platelet
      activating factor receptor antagonists CV-6209 and WEB 2086, as well as by the
      antioxidants vitamin E and 1,1,3,3-tetramethyl-2-thiourea. KB cells synthesized
      platelet-activating factor and the platelet-activating factor receptor agonist 1
      palmitoyl-2-acetyl-glycero-phosphocholine in response to tert-butyl hydroperoxide
      treatment, suggesting the augmentation of oxidative stress-induced signaling seen
      in platelet-activating factor receptor-expressing cells was due in part to
      endogenous platelet-activating factor biosynthesis. These studies suggest
      involvement of the epidermal platelet-activating factor receptors in oxidant
      mediated signaling.

PMID- 10084303
TI  - Depletion of cutaneous peptidergic innervation in HIV-associated xerosis.
AB  - Severe xerosis occurs in approximately 20% of human immunodeficiency virus
      seropositive patients. Changes in cutaneous innervation have been found in
      various inflammatory skin diseases and in xerotic skin in familial amyloid. We
      have therefore carried out a quantitative examination of the cutaneous
      peptidergic innervation in human immunodeficiency virus-associated xerosis.
      Immunohistochemistry and image analysis quantitation were used to compare total
      cutaneous innervation (protein gene product 9.5), calcitonin gene-related
      peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at
      two sites in the skin of human immunodeficiency virus-associated xerosis patients
      (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls
      (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each
      type was carried out for each subject in the epidermis and papillary dermis, and
      around the sweat glands. Immunostained mast cells in these areas were counted.
      Epidermal integrity and maturation were assessed by immunostaining for
      involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in
      total lengths of protein gene product 9.5 fibers in both epidermis/papillary
      dermis and sweat gland fields; of calcitonin gene-related peptide innervation in
      the epidermis/papillary dermis; and of substance P innervation of the sweat
      glands. There were no differences in the distribution of mast cells, or in the
      epidermal expression of involucrin. Depletion of the calcitonin gene-related
      peptide innervation may affect the nutrient blood supply of the upper dermis, and
      the integrity and function of basal epidermis and Langerhans cells. Diminished
      substance P innervation of the sweat glands may affect their secretory activity.
      Both of these changes may be implicated in the development of xerosis.

PMID- 10084304
TI  - Clusterin gene expression mediates resistance to apoptotic cell death induced by
      heat shock and oxidative stress.
AB  - Clusterin is a widely expressed, well conserved, secreted glycoprotein, which is
      highly induced in tissues regressing as a consequence of apoptotic cell death in
      vivo. It has recently been shown that clusterin expression is only confined to
      surviving cells following the induction of apoptosis in vitro, suggesting that it
      is involved in cell survival rather than death. In the hypothesis that clusterin
      may be implicated in cellular responses to stress, clusterin gene expression was
      analyzed in the A431 human epidermoid cancer cell line following heat shock and
      oxidative stress. Our results show that both a transient heat shock (20 min at 42
      degrees C) and various oxidative stresses, including hydrogen peroxide,
      superoxide anion, hyperoxia and UVA exposure, induce a strong increase in
      clusterin mRNA levels as assessed by northern blot. Nuclear run-on analysis
      suggests that transcriptional activation is involved in inducing clusterin mRNA
      in response to heat shock. Using pulse-chase analysis of control and heat shocked
      cells, it is shown that clusterin mRNA is translated and secreted, thus resulting
      in increased extracellular levels of the protein following heat shock. To
      investigate the function of clusterin in response to these stresses, clusterin
      anti-sense transfectants that stably express virtually no clusterin at the mRNA
      and protein level were generated in A431 cells. These anti-sense transfectants
      are shown to be highly sensitive to apoptotic cell death induced by heat shock or
      oxidative stress compared with wild-type A431 cells or control transfectants.
      Taken together, our results show that clusterin gene expression is induced in
      response to heat shock and oxidative stress in human A431 cells, and confers
      cellular protection against heat shock and oxidative stress.

PMID- 10084305
TI  - Particle-mediated gene transfer of PDGF isoforms promotes wound repair.
AB  - Several techniques for cutaneous gene transfer have been investigated for either
      in vitro or in vivo applications. In the present study, we investigated whether
      the direct delivery of platelet-derived growth factor cDNA into skin results in
      improvement in tissue repair. Cutaneous transfections were carried out in rats
      using a particle-bombardment device (Accell). As revealed by reverse
      transcriptase-polymerase chain reaction, transgene expression in vivo was
      transient, with low level expression by day 5. When compared with wounds
      transfected with a control cytomegalovirus-luciferase plasmid, wounds transfected
      with platelet-derived growth factor A or B in the MFG vector showed a significant
      increase in wound tensile strength 7 and 14 d after transfection. At both time
      points platelet-derived growth factor A transfected wounds exhibited the highest
      increase in tensile strength over controls, resulting in a 3.5-fold increase at
      day 7 and a 1.5-fold increase at day 14. The degree of stimulation was not
      remarkably different between wounds transfected with platelet-derived growth
      factor B, which is predominantly cell associated, or a truncation mutant,
      platelet-derived growth factor B211, which is predominantly secreted. These
      findings demonstrate that in vivo gene transfer by particle bombardment can be
      used to improve the tissue repair response. This approach provides a robust tool
      to assess the biologic activity of various proteins and will aid in the
      development of therapeutic cutaneous gene delivery.

PMID- 10084306
TI  - Induction of selected lipid metabolic enzymes and differentiation-linked
      structural proteins by air exposure in fetal rat skin explants.
AB  - The epidermal permeability barrier of premature infants matures rapidly following
      birth. Previous studies suggest that air exposure could contribute to this
      acceleration, because: (i) development of a structurally and functionally mature
      barrier accelerates when fetal rat skin explants are incubated at an air-medium
      interface, and (ii) occlusion with a water-impermeable membrane prevents this
      acceleration. To investigate further the effects of air exposure on epidermal
      barrier ontogenesis, we compared the activities of several key enzymes of lipid
      metabolism and gene expression of protein markers of epidermal differentiation in
      fetal rat skin explants grown immersed versus air exposed. The rate-limiting
      enzymes of cholesterol (HMG CoA reductase) and ceramide (serine palmitoyl
      transferase) synthesis were not affected. In contrast, the normal developmental
      increases in activities of glucosylceramide synthase and cholesterol
      sulfotransferase, responsible for the synthesis of glucosylceramides and
      cholesterol sulfate, respectively, were accelerated further by air exposure.
      Additionally, two enzymes required for the final stages of barrier maturation and
      essential for normal stratum corneum function, beta-glucocerebrosidase, which
      converts glucosylceramide to ceramide, and steroid sulfatase, which desulfates
      cholesterol sulfate, also increased with air exposure. Furthermore, filaggrin and
      loricrin mRNA levels, and filaggrin, loricrin, and involucrin protein levels all
      increased with air exposure. Finally, occlusion with a water-impermeable membrane
      prevented both the air-exposure-induced increase in lipid enzyme activity, and
      the expression of loricrin, filaggrin, and involucrin. Thus, air exposure
      stimulates selected lipid metabolic enzymes and the gene expression of key
      structural proteins in fetal epidermis, providing a biochemical basis for air
      induced acceleration of permeability barrier maturation in premature infants.

PMID- 10084307
TI  - Procyanidin oligomers selectively and intensively promote proliferation of mouse
      hair epithelial cells in vitro and activate hair follicle growth in vivo.
AB  - We have previously reported that proanthocyanidins extracted from grape seeds
      possess growth-promoting activity toward murine hair epithelial cells in vitro
      and stimulate anagen induction in hair cycle progression in vivo. This report
      constitutes a comparison of the growth-promoting activity of procyanidin
      oligomers and the target cells of procyanidins in the skin. Results show that
      procyanidin dimer and trimer exhibit higher growth-promoting activity than the
      monomer. The maximum growth-promoting activity for hair epithelial cells with
      procyanidin B-2, an epicatechin dimer, reached about 300% (30 microM) relative to
      controls (= 100%) in a 5 d culture. Optimum concentration of procyanidin C-1, an
      epicatechin trimer, was lower than that of procyanidin B-2; the maximum growth
      promoting activity of procyanidin C-1 was about 220% (3 microM). No other
      flavonoid compounds examined exhibit higher proliferative activities than the
      procyanidins. In skin constituent cells, only epithelial cells such as hair
      keratinocytes or epidermal keratinocytes respond to procyanidin oligomers.
      Topical application of 1% procyanidin oligomers on shaven C3H mice in the telogen
      phase led to significant hair regeneration [procyanidin B-2, 69.6% +/- 21.8%
      (mean +/- SD); procyanidin B-3, 80.9% +/- 13.0%; procyanidin C-1, 78.3% +/- 7.6%]
      on the basis of the shaven area; application of vehicle only led to regeneration
      of 41.7% (SD = 16.3%). In this paper, we demonstrate the hair-growing activity of
      procyanidin oligomers both in vitro and in vivo, and their potential for use as
      agents to induce hair growth.

PMID- 10084308
TI  - Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation
      in the pathogenesis of advanced cutaneous lymphomas.
AB  - There is evidence that the incidence of primary cutaneous lymphoma, like other
      forms of non-Hodgkin's lymphoma, is increasing, yet little is known of the
      pathogenetic events involved in this group of disorders. In this study we examine
      the frequency and spectrum of P53 gene mutations in a large series of primary
      cutaneous lymphomas, with particular emphasis on tumor stage mycosis fungoides,
      as it is in these cases that p53 overexpression has previously been reported.
      Sixty-six samples from 55 patients with primary cutaneous B cell and T cell
      lymphomas were analyzed for mutations in exons 5-9 of the P53 gene using
      polymerase chain reaction/single strand conformational polymorphism, and
      subsequent cloning and sequencing of genomic DNA. Fourteen separate P53 mutations
      were identified in blood, skin, and lymph node samples in 13 patients (24%).
      Twelve of 14 mutations occurred at dipyrimidine sites, eight resulting in C-->T
      transitions and one in a CC-->TT tandem base transition, a mutation spectrum
      strikingly similar to that reported in nonmelanoma skin cancer and characteristic
      of DNA damage caused by ultraviolet B radiation. In the subset of patients with
      mycosis fungoides, P53 mutations were identified in six of 17 patients with tumor
      stage but in none of 12 patients with plaque-stage disease (Fisher's exact test p
      = 0.027). These data suggest a role for ultraviolet radiation in the pathogenesis
      of primary cutaneous lymphomas and a possible ultraviolet B-related step in the
      progression of mycosis fungoides from plaque to tumor-stage disease.

PMID- 10084309
TI  - In vivo UVA-1 and UVB irradiation differentially perturbs the antigen-presenting
      function of human epidermal Langerhans cells.
AB  - Ultraviolet B (UVB, 290-320 nm) radiation is known to suppress the immune
      function of epidermal Langerhans cells. We have recently described that in vitro
      UVB irradiation perturbs the antigen-presenting cell function of Langerhans cells
      by inhibiting their expression of functional B7 costimulatory molecules (B7-1, B7
      2). The aim of this study was to determine wavelength-specific UV effects on
      Langerhans cells function in vivo, specifically UVB and UVA-1. To address this
      issue, volunteers were irradiated on the sun protected volar aspects of their
      forearms with 3 x minimal erythema dose of UVB (Philips TL-12) and UVA-1 (UVASUN
      5000 Mutzhaas). Langerhans cells were isolated from suction blister roofs
      immediately following irradiation. Langerhans cells isolated from UVB- but not
      from UVA-1-irradiated skin failed to activate naive resting allogeneic T cells
      (mixed epidermal cell leukocyte reaction) or primed tetanus toxoid reactive
      autologous T cells. Langerhans cells isolated from sham-irradiated or UVA-1
      irradiated skin strongly upregulated B7-2 molecules during short-term tissue
      culture. By contrast, Langerhans cells from UVB-irradiated skin did not
      upregulate B7-2 molecules. Furthermore, exogenous stimulation of the B7 pathway
      by anti-CD28 stimulatory monoclonal antibodies restored the capacity of UVB
      irradiated Langerhans cells to activate both alloreactive and tetanus toxoid
      reactive T cells, implying suppressed antigen-presenting cell activities and
      perturbed B7 expression of Langerhans cells isolated from UVB-irradiated skin are
      related. Those studies demonstrate that in vivo UVB, but not UVA-1, interferes
      with the activation-dependent upregulation of B7 molecules on Langerhans cells,
      which in turn is of functional relevance for the perturbed antigen-presenting
      cell function of Langerhans cells within UVB- but not UVA-1-irradiated skin.

PMID- 10084310
TI  - In situ repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in human
      skin exposed to solar simulating radiation.
AB  - DNA repair is crucial to the integrity of the human genome. The ultraviolet
      radiation portion of solar radiation is responsible for the rising incidence of
      skin cancer, one of the most common types of cancer in humans. We applied a
      recently developed 32P-postlabeling technique to measure the in situ DNA repair
      efficiency of solar-simulated radiation induced cyclobutane pyrimidine dimers and
      6-4 photoproducts in the skin of nine healthy volunteers with skin type II. Our
      results show about 6-fold interindividual variations in the level of DNA damage
      after exposure to an equal biologic dose - 2 minimal erythema doses. The kinetics
      of DNA repair indicated a base sequence dependence of the repair process. The DNA
      repair efficiency showed a 20-fold difference in volunteers. An age-related
      decrease of DNA repair capacity was observed; however, the data are limited due
      to a small number of subjects and a narrow age range. The variable response in
      DNA damage levels and individual differences in DNA repair efficiency suggest a
      susceptible subgroup of people probably with a higher skin cancer risk.

PMID- 10084311
TI  - Influence of increased c-Myc expression on the growth characteristics of human
      melanoma.
AB  - Overexpression of the proto-oncogene c-myc has been associated with neoplastic
      transformation in a variety of tumors. For human melanoma high c-myc expression
      has been found in the vertical growth phase and higher positivity reported in
      metastases than primary tumors. The principle aim of this study was to determine,
      whether c-Myc expression influences the metastatic behavior of human melanoma in
      the absence of lymphocyte-mediated immune phenomena. The growth characteristics
      and tumor biology of two c-myc transfectants of the human melanoma cell line
      IGR39D, expressing c-Myc 1.7 and three times over baseline and the respective
      vector control were analyzed both in vitro and in a severe combined
      immunodeficient mouse model in vivo. Both c-myc transfectants showed increased
      growth rates, anchorage independent growth and directed cell movement in culture.
      Subcutaneously implanted IGR39D melanomas highly overexpressing c-Myc
      spontaneously formed macroscopic metastases (lymph nodes and lung) in severe
      combined immunodeficient mice in all cases (n = 7 per group), whereas less
      prominent c-Myc overexpression caused the development of only lung
      micrometastases. During the time period leading to terminal disease in animals
      injected with c-myc transfected human melanoma cells, melanoma development was
      not seen in vector controls. These findings suggest that constitutive high c-Myc
      expression in human melanoma results in a more aggressive growth behavior both in
      vitro and in vivo and favors metastasis in severe combined immunodeficient mice
      by factors unrelated to immune phenomena such as class I human leukocyte antigen
      downregulation known to be associated with c-Myc expression.

PMID- 10084312
TI  - Evidence for a novel glutamate-mediated signaling pathway in keratinocytes.
AB  - Phenotypic alterations in keratinocyte behavior are essential for maintaining
      epidermal integrity during growth and wound repair and rely on co-ordinated cell
      signaling events. Numerous growth factors and cytokines have been shown to be
      instrumental in guiding such changes in keratinocyte activity; here we provide
      evidence which proposes a novel epidermal signaling pathway mediated by the
      excitatory amino acid glutamate. Glutamate is the major excitatory
      neurotransmitter at synaptic junctions within the central nervous system;
      however, we have identified expression in vivo of several regulatory molecules
      associated with glutamate signaling in keratinocytes. In resting rat skin
      epidermis, different classes of glutamate receptors, transporters, and a recently
      described clustering protein were shown to display distinct distribution
      patterns, supportive of a multifunctional cellular communication pathway.
      Immunoreactive N-methyl-D-aspartate-type, alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate-type, and metabotropic-type glutamate receptors were
      colocalized with the specific glutamate transporter EAAC1 in basal layer
      keratinocytes, and GLT-1, a related transporter, was expressed suprabasally. In
      full-thickness rat skin wounds, marked modifications in the distribution of N
      methyl-D-aspartate receptors and EAAC1 were observed during re-epithelialization,
      and alterations in N-methyl-D-aspartate receptor expression accompanied embryonic
      epidermal development, implicating glutamate signaling in these important
      biologic events. Furthermore, we provide evidence that these receptors are
      functional in vitro. These data provide strong evidence to support a role for
      glutamate in the control of epidermal renewal, and therefore suggest potentially
      novel therapeutic targets for the treatment of skin disease and enhancement of
      wound healing.

PMID- 10084313
TI  - Epidermal organization and differentiation of HaCaT keratinocytes in organotypic
      coculture with human dermal fibroblasts.
AB  - The immortal human keratinocyte line HaCaT is frequently used as a paradigm for
      skin keratinocytes in vitro because of its highly preserved differentiation
      capacity. HaCaT cells form a nearly regular epidermal architecture when
      transplanted onto subcutaneous tissue of athymic mice. In order to analyze
      further their differentiation capacity in vitro, HaCaT cells were studied in
      organotypic cocultures on top of collagen gels containing human dermal
      fibroblasts. Within 1 wk HaCaT cells formed a still dysplastic epithelium, the
      thickness of which correlated with the number of fibroblasts in the collagen gel.
      With further culture time of up to 3 wk a remarkably well structured and
      differentiated squamous epithelium developed. After 1 wk, keratins 10 and 16,
      involucrin, and transglutaminase I were expressed in suprabasal layers, whereas
      filaggrin, keratin 2e, and loricrin appeared after 2-3 wk. Within this time, a
      nearly complete basement membrane had formed including hemidesmosomes and
      anchoring fibrils. Epithelial cell proliferation became restricted to the basal
      layer after 2 and 3 wk. Using the TdT-mediated dUTP nick end labeling assay,
      fragmentation of DNA was detectable in nuclei of the parakeratotic stratum
      corneum. Ultrastructurally, many features of keratinization accumulated after 2
      and 3 wk, though an orthokeratotic keratinization was not achieved, in contrast
      to HaCaT transplants. This differentiation deficiency - as compared with normal
      keratinocytes -- might be due to a lack of paracrine factors important for
      keratinocyte differentiation or to a reduced sensitivity of these cells.
      Nevertheless, this high degree of differentiation under organotypic conditions
      qualifies this cell line as an appropriate model for elucidation of the molecular
      mechanisms regulating keratinocyte growth and differentiation and for use in
      pharmacotoxicology.

PMID- 10084314
TI  - Upregulation of connexin 26 is a feature of keratinocyte differentiation in
      hyperproliferative epidermis, vaginal epithelium, and buccal epithelium.
AB  - In epidermis, it has been suggested, intercellular communication through gap
      junctions is important in coordinating cell behavior. The connexins, may
      facilitate selective assembly or permeability of gap junctions, influencing the
      distribution of metabolites between cells. Using immunohistochemistry, we have
      compared the distribution of connexins 26 and 43 with that of proliferating cells
      (Ki67 labeling) in normal epidermis, hyperplastic epidermis (tape-stripped
      epidermis, psoriatic lesions, and viral warts), and vaginal and buccal epithelia.
      Connexin 43 was abundant in spinous layers of all epidermal specimens and in
      vaginal and buccal epithelia. Connexin 26 was absent from the interfollicular and
      interductal epidermis of normal hair-bearing skin, and nonlesional psoriatic
      epidermis but present at very low levels in plantar epidermis. Connexin 26 was
      prominent in lesional psoriatic epidermis and viral warts and in vaginal and
      buccal epithelia. In three independent experiments connexin 26 appeared in a
      patchy intercellular distribution in the basal epidermis within 24 h of tape
      stripping, proceeding to more extensive distribution in basal and suprabasal
      layers by 48 h. The increase in connexin 26 preceded that in cell proliferation.
      In vaginal epithelium, buccal epithelium, and viral warts connexin 26 was
      restricted mainly to suprabasal, nonproliferating cells. In psoriatic lesional
      epidermis connexin 26 was also located mainly in suprabasal, nonproliferating
      cells. Connexin 26 was present in a patchy distribution in the basal layer of
      psoriatic lesional epidermis, but double labeling for connexin 26 and Ki67 showed
      that many connexin 26 positive basal cells were nonproliferative, suggesting that
      connexin 26 may be related to differentiation rather than to proliferation. These
      observations would be consistent with a role for connexin 26 containing gap
      junctions during both early and later stages of keratinocyte differentiation in
      hyperplastic epidermis and in vaginal and buccal epithelia.

PMID- 10084315
TI  - Keratin 15 expression in stratified epithelia: downregulation in activated
      keratinocytes.
AB  - Keratin 15 (K15) is a type I keratin without a defined type II partner whose
      expression in epidermal diseases has not been investigated. In this study we have
      used LHK15, a monoclonal antibody raised against the last 17 amino acids of the
      K15 polypeptide, to show that K15 is expressed primarily in the basal
      keratinocytes of stratified tissues, including the fetal epidermis and fetal
      nail. Although K15 in normal hair follicles was virtually absent from hair bulbs,
      it was expressed by a subset of keratinocytes in the outer root sheath. By
      comparison, K14 expression was found throughout the outer root sheath of hair
      follicles; however, when both K14 alleles were naturally ablated, the expression
      of K15 was also observed throughout the outer root sheath of the follicles.
      Expression of K15 mRNA was assessed by in situ hybridization and corroborated the
      data from immunostaining. An increase in K15 mRNA and protein expression in hair
      follicles from the K14 ablated epidermis suggested an upregulation of the K15
      gene in the absence of the K14 protein. In organotypical cultures where
      differentiating keratinocytes expressed markers of activated phenotype, i.e., K6
      and K16, expression of K15 was undetectable. The expression of K15 mRNA and
      protein was also downregulated in two hyperproliferating situations, psoriasis
      and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars
      are activated, we conclude that K15 expression is not compatible with
      keratinocyte activation and the K15 gene is downregulated to maintain the
      activated phenotype.

PMID- 10084316
TI  - Topical gene delivery to murine skin.
AB  - We topically applied naked plasmid DNA containing the luciferase or
      chloramphenicol acetyltransferase cDNA directly to mouse skin. Gene expression
      was detected in skin samples as early as 4 h after DNA application, plateaued
      from 16 to 72 h post-application, and had decreased significantly by 7 d post
      application. Reporter gene activity following topical DNA delivery was comparable
      with that produced by intradermal injection of DNA. Plasmid DNA at concentrations
      > or =0.25 microg per microl were required to achieve maximal expression levels.
      Reporter gene expression following topical administration was largely confined to
      the superficial layers of the epidermis and to hair follicles. Surprisingly,
      certain cationic liposomes inhibited the efficiency of cutaneous gene transfer.
      This technique provides a simple, clinically relevant approach to deliver genes
      to the skin, with potential application in treating a variety of cutaneous
      disorders.

PMID- 10084317
TI  - A novel glutamic acid to aspartic acid mutation near the end of the 2B rod domain
      in the keratin 1 chain in epidermolytic hyperkeratosis.
AB  - We report a mutation in a mild case of epidermolytic hyperkeratosis that results
      in a glutamic acid to aspartic acid substitution in a novel location, codon 477
      or position 106 of the 2B rod domain of the keratin 1 chain. This residue has
      been conserved in all intermediate filament chains and lies near the beginning of
      the highly conserved helix termination sequence and just prior to the predicted
      molecular overlap region. Keratin filaments assembled in vitro from chains
      bearing this substitution are abnormal, indicating that the glutamic acid residue
      is critically involved in ionic interactions in intermediate levels of filament
      structure.

PMID- 10084318
TI  - A novel mutation in the 1A domain of keratin 2e in ichthyosis bullosa of Siemens.
AB  - Ichthyosis bullosa of Siemens (IBS) is a rare autosomal dominant skin disorder
      with clinical features similar to epidermolytic hyperkeratosis (EHK). Both
      diseases have been linked to the type II keratin cluster on chromosome 12q.
      Hyperkeratosis and blister formation are relatively mild in IBS compared with
      EHK, and the lysis of keratinocytes is restricted to the upper spinous and
      granular layers of the epidermis of IBS patients, whereas in EHK lysis occurs in
      the lower spinous layer. Recently, mutations in the helix initiation and
      termination motifs of keratin 2e (K2e) have been described in IBS patients. The
      majority of the mutations reported to date lie in the 2B region. In this report,
      we have examined a large kindred in which the disease was originally diagnosed as
      EHK and mapped to the type II keratin cluster on chromosome 12q. Molecular
      analysis revealed a novel amino acid substitution at the beginning of the
      conserved 1A region of the rod domain (I4N) of K2e, resulting from a T to A
      transversion in codon 188.

PMID- 10084319
TI  - In vivo expression and localization of Candida albicans secreted aspartyl
      proteinases during oral candidiasis in HIV-infected patients.
AB  - Isoforms of aspartyl proteinase (Sap), which are encoded by at least nine related
      SAP genes, have been implicated to be a major virulence factor of the
      opportunistic yeast Candida albicans in experimental infections. Although it is
      generally assumed that proteinases are important for infections, detailed
      information on the pathogenetic role of Saps is still lacking. The same applies
      to the question whether the genes and corresponding isoforms of the enzyme are
      expressed during oral infection. For in vivo investigations, parts of the
      lesional oral epithelium were collected from three HIV-infected patients with
      oropharyngeal candidiasis. Immunoelectron microscopy was performed (pre- and post
      embedding gold labeling with silver enhancement) using an anti-Sap murine
      monoclonal antibody directed against the gene products Sap1-3. It was possible to
      demonstrate expression of Sap antigens in each of the three samples of human oral
      candidiasis. This suggests that at least one of the genes SAP1-3 was expressed at
      the time of sample collection. Furthermore, a possible role of the enzymes during
      the interaction of yeast cells and mucosal cells is suggested: the majority of
      Sap antigens is secreted by those C. albicans cells that adhere directly to the
      epithelial surface. Sap immunoreactivity can be detected in particular at the
      site of close contact between C. albicans and epithelial cells, suggesting a
      pathogenetic role of the Saps in host-fungal interaction. Thus, inhibition of the
      enzyme might prove to be an important alternative in the prevention and treatment
      of candidiasis.

PMID- 10084320
TI  - Human dermal microvascular endothelial cells express inducible nitric oxide
      synthase in vitro.
AB  - Stimulation of inducible nitric oxide synthase with subsequent release of nitric
      oxide in large amounts may play a critical part either in host defense reactions
      or in the pathophysiology of the inflammatory response syndrome leading to septic
      shock. The aim of the present study was to investigate whether human dermal
      microvascular endothelial cells exhibit the typical characteristics of an
      inducible nitric oxide synthase expressing cell. A strong effect on inducible
      nitric oxide synthase gene expression could be detected when the cells were
      coincubated with the proinflammatory cytokines interferon-gamma and tumor
      necrosis factor-alpha with inducible nitric oxide synthase cDNA concentrations
      averaging 11.7 +/- 0.6 amol per microg total RNA at 24 h, and 25.0 +/- 1.4 amol
      per microg total RNA at 48 h, respectively. Intracellular staining with an
      antibody recognizing inducible nitric oxide synthase protein and subsequent
      analysis by flow cytometry revealed a 4-fold increase of inducible nitric oxide
      synthase protein in human dermal microvascular endothelial cells treated with
      interferon-gamma/tumor necrosis factor-alpha. This was accompanied by a
      significant elevation in nitrite/nitrate concentrations in the cell-free culture
      supernatants. Our results indicate that human dermal microvascular endothelial
      cells are provided with an inducible nitric oxide synthase system and can be
      regarded as an appropriate cell model for investigating inducible nitric oxide
      synthase gene expression and nitric oxide properties in microvascular endothelial
      cells.

PMID- 10084321
TI  - Cultured epithelial autograft "take" confirmed by the presence of cytokeratin 9.

PMID- 10084322
TI  - Notable losses at specific regions of chromosomes 10q and 13q in the Sezary
      syndrome detected by comparative genomic hybridization.

PMID- 10084323
TI  - Erythema multiforme associated human autoantibodies against desmoplakin I and II.

PMID- 10084324
TI  - Elevated serum levels of interleukin-6 in paraneoplastic pemphigus.

PMID- 10084325
TI  - Clustering of COL7A1 mutations in exon 73: implications for mutation analysis in
      dystrophic epidermolysis bullosa.

PMID- 10084326
TI  - The role of mandated research during dermatology residency training.

PMID- 10084327
TI  - Effects of in vivo administration of adamantylamide dipeptide on bone marrow
      granulocyte-macrophage hemopoietic progenitor cells (GM-CFC) and on ability of
      serum of the treated mice to stimulate GM-CFC colony formation in vitro:
      comparison with muramyl dipeptide and glucan.
AB  - Adamantylamide dipeptide (AdDP), muramyl dipeptide (MDP), and glucan were shown
      to increase significantly the numbers of granulocyte-macrophage hemopoietic
      progenitor cells (GM-CFC) in the bone marrow of mice. However, whereas the sera
      of mice given MDP or glucan were found to stimulate the growth of colonies from
      GM-CFC in vitro, i.e. to produce a colony-stimulating activity (CSA),
      administration of AdDP did not lead to this effect. Nevertheless, when serum of
      mice given AdDP was added to the cultures concomitantly with a suboptimal
      concentration of mouse interleukin-3 (mIL-3), a broad spectrum hemopoietic
      stimulator, counts of colonies from GM-CFC were significantly increased, and
      accelerated growth of the colonies was found as well. This property of AdDP, i.e.
      its ability to exhibit co-stimulating activity (CoSA) without being able to
      exhibit CSA, suggests that AdDP acts in hemopoietic tissues differently as
      compared with the two other immunomodulators studied. It can be hypothesized that
      the action of AdDP is more specific when compared with its natural related
      compound, MDP, as well as with glucan. Our findings prove the possibility to
      stimulate by AdDP the granulopoietic compartment of hemopoiesis and are in
      agreement with previous observations concerning the absence of systemic side
      effects of AdDP. Both these qualities of AdDP may be advantageous when pondering
      over contingent clinical utilization of AdDP as hemopoietic stimulator.

PMID- 10084328
TI  - Abnormal functional behavior of peripheral blood mononuclear cells from
      Hashimoto's disease patients. Immunomodulatory effects of cyclosporin A.
AB  - In vitro studies of activation and proliferation induced by mitogens in the
      presence of Cyclosporin A (CsA) and or cytokines were carried out to determine
      the effects of CsA and cytokines on mitogen activated peripheral blood
      mononuclear cells (PBMC) from thirteen Hashimoto's disease patients (HP) and ten
      healthy controls. The proliferative response (PR) of PBMC from HP to mitogens at
      7 days of culture was higher than in controls. Interleukin 2 (IL-2) addition
      significantly increased the PR in phytohemagglutinin-stimulated PBMC from HP, but
      not in controls. CsA inhibited in a dose dependent manner the PR, as well as the
      expression of activation antigens induced by mitogens in both groups of subjects,
      but PBMC from HP were sensitive to CsA at lower doses than those that were
      effective on PBMC from controls. Both IL-2 or IL-4 overcame the inhibitory effect
      of CsA on PBMC from HP and controls. Conversely, IL-10 or IFN-alpha addition
      increases the inhibitory effect of CsA on the PR of PBMC from both HP and
      controls. We conclude that PBMC from Hashimoto's disease patients shown an
      abnormal pattern of PR that is associated to increased PR to mitogens and higher
      sensitivity to immunomodulatory effects of IL-2 and CsA.

PMID- 10084329
TI  - In vitro measurement of lymphocyte steroid sensitivity: lack of agreement between
      whole blood culture and separated lymphocyte culture.
AB  - The use of a whole blood culture to measure steroid sensitivity has previously
      been compared to the use of a separated lymphocyte assay. Good correlation
      between the two methods was reported. However the number of subjects studied
      appears to have been small and no patients with steroid resistance were studied.
      We have studied a large number of subjects and compared steroid sensitivity
      measured by a whole blood culture with an established separated lymphocyte assay.
      Proliferation was stimulated with phytohaemagglutinin and inhibited by
      dexamethasone. A wide range of steroid sensitivity was found between individuals.
      In steroid sensitive subjects, good agreement was seen between the two assays.
      However in individuals identified as steroid resistant by the separated
      lymphocyte assay, steroid resistance was not seen using the whole blood assay.
      This is important because in vitro lymphocyte steroid resistance, as measured by
      the separated lymphocyte assay has been shown to predict a poor in vivo response
      to steroid therapy. Using the whole blood culture this steroid resistance would
      not be demonstrated. Hence the use of a whole blood assay can not be recommended.

PMID- 10084330
TI  - Simultaneous amplification of Bordetella repeated insertion sequences and toxin
      promoter region gene by polymerase chain reaction.
AB  - A polymerase chain reaction was devised to simultaneously detect repeated
      insertion sequences and the pertussis toxin promoter gene for the diagnostic
      identification of Bordetella pertussis, B. parapertussis, and B. bronchiseptica.
      The sensitivity of this method was sufficient to detect one B. pertussis organism
      using the following cycles and temperatures: 95 degrees C for 15 min, followed by
      32 amplification cycles (1 min at 95 degrees C, 1 min at 66 degrees C, 1 min at
      72 degrees C), and finally 5 min at 72 degrees C. Using the primers as a combined
      set did not affect sensitivity, but required an increased temperature for optimal
      annealing compared with a single-sequence assay. As nasopharyngeal aspirate and
      swab materials sometimes contain hemoglobin, we also tested the inhibitory effect
      of hemoglobin on this assay, which was inhibited completely when using DNA
      extracts from samples containing hemoglobin at a final concentration >0.015 g/L:
      this inhibition was reversed by addition of bovine serum albumin to the buffer.
      Our assay shows promising sensitivity and specificity for clinical use.

PMID- 10084331
TI  - Ethanol impairs major histocompatibility complex (MHC) class II molecule-mediated
      but not MHC class I molecule-mediated T cell response in alcohol-consuming mice.
AB  - The goal of this study was to determine whether alcohol affects alloantigen
      induced proliferative and cytolytic activity of T cells in mice, and whether the
      altered immune response was in part due to a defect of IL-2 activity. The ability
      of spleen cells from individual alcohol-consuming C57BL/6 mice to generate allo
      specific mixed lymphocyte response (MLR) and cytotoxic T lymphocyte (CTL) was
      compared to that of mice fed on an isocaloric maltose diet and regular diet.
      Allospecific MLR and CTL were generated by sensitizing spleen cells of C57BL/6
      mice against spleen cells from BALB/c mice, and the allo-specific CTL activity
      was determined by the ability of the CTL to kill 51Cr-labeled P815 mastocytoma
      target cells. Our results showed that the allo-specific MLR of the responder
      cells from alcohol-consuming mice was significantly reduced (40% reduction, p<0.0
      1), and the addition of exogenous interleukin 2 (IL-2) could not reverse the
      suppression of MLR induced by ethanol. However, our results clearly showed that
      ethanol has little suppressive effect on allo-reactive CTL of alcohol-consuming
      mice as compared to the alloreactivity of the control mice (P>0.05). Finally, we
      also demonstrated that ethanol did not impair the alloantigen-induced IL-2
      production in the mixed lymphocyte cultures (P>0.1).

PMID- 10084332
TI  - Ehrlich's ascites fluid adsorbed over protein A containing Staphylococcus aureus
      Cowan I produces inhibition of tumor growth.
AB  - Our earlier studies have shown that removal of various blocking factors from the
      sera of tumor-bearing animals and humans by adsorption over heat-attenuated and
      formalin-fixed-Staphylococcus aureus Cowan I (SAC) containing Protein A (PA)
      causes antitumor immune response. It was also shown that this procedure caused
      regression of a wide variety of established animal and human tumors. In the
      present investigation, the therapeutic potential of inoculation of ascites fluid
      adsorbed in vitro over non-viable SAC containing PA has been demonstrated in
      Ehrlich' s ascites tumor (EAT) in mouse. The antitumor effect was evident by a
      significant decrease in body weight (p<0.001) as well as significant reduction in
      viability of ascites tumor cells (p<0.001) in peritoneal cavity. However, some of
      the responding animals died earlier than controls, this may be due to the
      toxicity associated with therapy. The toxic effects were evident in decreased
      contents of glutathione, and increased activity of glutathione-S-transferase,
      decreased activity of microsomal enzymes and also in an early death of some of
      tumor regressed animals. The probable causes of toxicity of the therapy and
      prospects of reversing these toxic effects are discussed.

PMID- 10084333
TI  - Petiveria alliacea L. extract protects mice against Listeria monocytogenes
      infection--effects on bone marrow progenitor cells.
AB  - In this study we have investigated the effects of Petiveria alliacea on the
      hematopoietic response of mice infected with Listeria monocytogenes. Our results
      demonstrate a protective effect of the crude extract of P. alliacea since the
      survival of the treated/infected was higher than that in the infected group.
      Moreover, the number of granulocyte/macrophage colonies (CFU-GM) and the serum
      colony stimulating activity levels were increased in the treated/infected mice in
      relation to the infected group. These results suggest an immunomodulation of
      Petiveria alliacea extract on hematopoiesis, which may be responsible, at least
      in part, for the increased resistance of mice to Listeria monocytogenes
      infection.

PMID- 10084334
TI  - Inhibition of eosinophil infiltration into the mouse peritoneal cavity by a
      traditional Chinese medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to).
AB  - Our previous study showed that the serum level of antigen-specific IgE antibodies
      in primary response was decreased by a traditional Chinese medicine, Bu-zhong-yi
      qi-tang (Japanese name; Hochu-ekki-to, HOT). In this study, we examined
      inhibition of secondary IgE response and of eosinophil infiltration by HOT.
      BALB/c mice were intraperitoneally immunized with aluminum hydroxide adsorbed
      with DNP-KLH (DNP-KLH + alum) on day -14 and on day 0. In mice treated with HOT
      daily from day -14, the serum level of antigen-specific IgE antibodies after the
      secondary immunization was significantly decreased compared to that in mice not
      treated with HOT. Eosinophils increased in number after 6 and 24 hr, and CD4+ T
      cells in the peritoneal cavity increased in number 24 hr after the secondary
      immunization. HOT suppressed accumulation of eosinophils and CD4+ T cells in the
      peritoneal cavity. Furthermore, HOT suppressed the numbers of IL-4- and IL-5
      producing cells 24 hr after the secondary immunization, but did not inhibit the
      number of IFN-gamma-producing cells. HOT also suppressed IL-5 mRNA expression.
      Furthermore, HOT also inhibited antigen-induced late-phase reaction (LPR) in the
      skin. These results suggested that HOT exhibited anti-allergic effects mainly by
      inhibiting Th2 cell responses.

PMID- 10084335
TI  - Presence of micronuclei in lymphocytes of mercury exposed workers.
AB  - We have investigated the presence of micronuclei in mercury exposed workers. The
      study group consisted of 15 workers from a mercury-producing plant, mean age 39.5
      years and a mean exposed period of 12 years. At the time of testing and for the
      six previous months, the exposed population had urinary mercury levels below the
      currently accepted limit of 50 ug/g creatinine. A significant increase in the
      percentage of micronuclei was observed in the mercury exposed individuals when
      compared to the non exposed group. We have not found any correlation between the
      percentage of micronuclei and age, length of exposure or urinary mercury
      concentrations. Our results suggest a genotoxic effect of mercury, which is
      observed in workers exposed chronically to levels considered biologically safe
      for the exposed population.

PMID- 10084336
TI  - Immunomodulatory activity of a Unani gold preparation used in Indian system of
      medicine.
AB  - Kushta Tila Kalan (KTK), a gold preparation used in Unani-Tibb is claimed to
      possess general tonic, anti-infective and rejuvenating properties. We evaluated
      immunomodulatory activity of KTK in male mice. KTK was orally administered to
      animals at dosage of 6.25, 12.5, 25 and 50 mg/kg b.w. for 10 days. Beside general
      immunopathological parameters, cell-mediated immunity was evaluated by measuring
      delayed type of hypersensitivity response (DTH) while humoral immunity was
      assessed using plaque forming cell (PFC) assay. KTK augmented both the immune
      responses at dose levels of 6.25, 12.5 and 25 mg/kg. The optimum activities were
      recorded at 25 mg/kg. High dose of 50 mg/kg showed suppressive effects on immune
      functions. The modulatory effects may be attributed to the interactions of gold
      with herbomineral adjuncts incorporated during the specialized ashing techniques
      used in the preparation. The results are interesting in view of reported
      suppressive effects of other gold preparations.

PMID- 10084337
TI  - Effect of Kumhwang-San on anaphylactic reaction in a murine model.
AB  - We investigated the effect of Kumhwang-San on anaphylactic reaction. Kumhwang-San
      dose-dependently inhibited mast cell-mediated systemic anaphylactic reaction
      induced by compound 48/80. Kumhwang-San significantly inhibited plasma histamine
      levels induced by compound 48/80. Kumhwang-San dose-dependently inhibited
      histamine release from the rat peritoneal mast cells activated by compound 48/80
      or substance P. The level of cAMP in rat peritoneal mast cells, when Kumhwang-San
      was added, transiently and significantly increased about 3-fold compared with
      that of basal cells. These results suggest that Kumhwang-San will be beneficial
      in the treatment of anaphylactic reaction.

PMID- 10084338
TI  - On psychiatry: some reflections circa 1998.

PMID- 10084339
TI  - From consultation-liaison psychiatry to psychosocial advocacy: maintaining
      psychiatry's scope.
AB  - OBJECTIVE: To review the status of consultation-liaison (C-L) psychiatry and the
      forces shaping it, and to propose strategies for dealing with the crisis in which
      it finds itself. METHOD: A Medline search of C-L psychiatry and related terms,
      together with hand-searching of C-L psychiatry and psychosomatic journals and
      bibliographies of found articles, was used for the literature base. The
      experience of membership of the committees of national and international C-L
      psychiatry organisations and their interaction with health care administrators
      was used as the basis for the discussion of strategies. RESULTS: It is argued
      that patients with physical/psychiatric comorbidity and somatisation have been
      marginalised by application of narrow definitions of what constitutes 'serious
      mental disorder' in the public sector. Evidence is presented to support the
      argument that physical/psychiatric comorbidity is the most common form of
      psychiatric presentation in the community, that such comorbidity has serious
      consequences in terms of morbidity, mortality and health-care costs, and that
      even subthreshold psychiatric symptoms have serious implications when physical
      comorbidity exists. CONCLUSION: It is concluded that a number of strategies,
      including pre-admission screening, integrated discharge planning, liaison, as
      well as shared care with general practitioners, advanced training in C-L
      psychiatry and more research to establish practice guidelines, are required if
      psychiatry is to remain a broad-based discipline rather than retreat to being a
      specialty for psychosis. Consultation-liaison psychiatrists must become the
      advocates for the psychosocial system.

PMID- 10084340
TI  - The diagnosis of depression in disorder.
AB  - OBJECTIVE: My purpose is to critically evaluate psychiatry's current approach to
      the diagnosis of depression. METHODS: I have closely examined trends in
      diagnosing depression, especially since DSM-III, and have considered alternative
      options. RESULTS/CONCLUSIONS: Psychiatric taxonomy is currently based on invalid
      nosological premises that have worked as a strait jacket for conceptual progress
      and related biological and psychopharmacological research. A fresh approach that
      replaces nosological analysis with the concepts of functionalisation and
      verticalisation is essential.

PMID- 10084341
TI  - Use of psychotropic medications in breast-feeding women: acute and prophylactic
      treatment.
AB  - OBJECTIVES: The postnatal period is a time of increased onset and relapse of
      mental illness. It poses a clinical dilemma, as many mothers requiring medication
      acutely or prophylactically will also choose to breast feed. The present paper
      first reviews the safety of psychotropes in breast-fed infants and the usefulness
      of prophylaxis for women at risk of postpartum affective relapse and, second,
      provides guidelines in the use of psychotropic drugs in breast-feeding women.
      METHODS: A Medline review was conducted reviewing all papers published during the
      period 1993-1998 (and their associated bibliographies) on the use of psychotropes
      in breast-feeding women and the prophylactic usefulness of medications in women
      at risk of affective postpartum relapse. RESULTS: Findings are based on case
      reports and small, mostly uncontrolled studies. Both tricyclic antidepressants
      (TCA) and specific serotonin re-uptake inhibitors (SSRIs) appear to be relatively
      safe in breast feeding. Antidepressants commenced in the early postpartum period
      may reduce depressive relapse. While prophylactic lithium appears to
      significantly reduce relapse of affective psychosis in the puerperium, there have
      been no studies of the anticonvulsants in the puerperium. Finally, high dose
      antipsychotics should be avoided, as they may be associated with long-term
      adverse sequelae in the infant. CONCLUSIONS: On the basis of current knowledge,
      the use of SSRIs, TCA, carbamazepine, sodium valproate and short-acting
      benzodiazepines in breast feeding is relatively safe. If lithium is to be used,
      close collaboration with a paediatrician is essential. The long-term risks of
      antipsychotics, especially at high doses, remain to be clarified. Before a
      decision can be made, the risk-benefit ratio must be clearly outlined and
      discussed with the mother and her partner.

PMID- 10084342
TI  - Psychiatrists and compulsion: a map of ethics.
AB  - OBJECTIVE: The aim of this study is to analyse the ethical underpinning of
      involuntary treatment and to create a guide for psychiatric practice which
      clarifies its relationship with modern mainstream clinical ethics. METHOD:
      Literature on ethics, involuntary treatment, civil commitment, diagnosis and law
      was searched and examined. RESULT: Hospitalisation for involuntary treatment and
      control has blurred two important discriminations: the discrimination between
      clinical and social constructions of mental illness and the discrimination
      between therapeutic actions and policing control. Plotting these discriminations
      creates a map of ethics in involuntary treatment. Although there are clinical
      roles throughout involuntary treatment, the ethical issues vary according to
      whether clinical actions are taken on clinically or socially constructed
      diagnosis and whether the purpose of the actions is therapy or control.
      CONCLUSION: Paternalist involuntary treatment should be undertaken more readily
      when it is for clinically defined illness and for the benefit of the patient.
      Where the conditions are defined by social behaviours alone, where treatment is
      not useful to the patient, or where actions have policing intent, particular
      ethical approaches need to be taken to defend the patient, the clinician-patient
      relationship and the reputation of the profession.

PMID- 10084343
TI  - Dissociative identity disorder: an Australian series.
AB  - OBJECTIVE: Series of patients fulfilling diagnostic criteria for Dissociative
      Identity Disorder (DID), otherwise known as multiple personality disorder, have
      particularly been reported on in North America and increasingly in other
      countries. The present study investigated the trauma and past treatment
      histories, symptom profiles and dissociative phenomenology of 62 patients
      fulfilling diagnostic criteria for DID seen in Brisbane (Queensland, Australia).
      METHOD: From 1992, systematic assessments, including the Dissociative Experience
      Scale and the Dissociative Disorders Interview Schedule, were performed with a
      personal series of 57 patients with DID seen by one of the authors (WM) and five
      patients seen by the second author (JB). RESULTS: The histories of childhood
      trauma, the clinical profiles and dissociative indices of these patients closely
      approximate those described in series reported in other countries. CONCLUSIONS:
      Patients fulfilling diagnostic criteria for DID are regularly seen in Australian
      inpatient and outpatient settings. The dissociative symptomatology of the
      patients examined in the present study represents a significant component of a
      complex syndrome associated with a history of severe ongoing developmental trauma
      dating from early childhood.

PMID- 10084344
TI  - Delirium in hospital: does it increase length of stay?
AB  - OBJECTIVE: To determine the effect of delirium, as a comorbid diagnosis in
      hospitalised patients, on patient length of stay (LOS). METHOD: Prospective study
      comparing LOS of delirious patients with controls matched by age, gender,
      principal diagnosis and date of admission. Medical and surgical inpatients of
      Westmead Hospital with delirium were identified from a Consultation Liaison (CL)
      psychiatry database and were matched with controls from the hospital medical
      records. RESULTS: Delirious patient LOS was found to be significantly longer (2.2
      fold; 95% confidence interval 1.5-3.3) than matched controls. CONCLUSIONS:
      Delirium, as a comorbid diagnosis in general hospital patients, is associated
      with an increased use of resources. Its early diagnosis may limit this and
      morbidity.

PMID- 10084345
TI  - Early intervention in schizophrenia in the elderly.
AB  - OBJECTIVE: The aim of this paper is to briefly review the literature on early
      intervention in schizophrenia in the elderly, and to present six cases of
      schizophrenia in the elderly which highlight the need for assertive management of
      the type encouraged widely for early onset illness in younger patients. METHOD:
      Six case histories are presented. RESULTS: All six patients were diagnosed with
      DSM-IV schizophrenia, all were single and all were socially isolated. They
      required involuntary admission, treatment with depot antipsychotics, extensive
      psychosocial intervention and community treatment orders. The use of these
      treatment strategies led to a positive outcome in each case. CONCLUSION: The
      authors argue that assertive treatment of elderly patients with schizophrenia
      should be pursued with the enthusiasm often reserved for younger, early onset
      patients, and that therapeutic optimism is required and warranted.

PMID- 10084346
TI  - Six-month outcome following a relapse of schizophrenia.
AB  - OBJECTIVE: To analyse clinical data on patients with schizophrenia on admission
      to acute care and 6 months later in order to identify factors associated with
      frequent hospitalisations and poor outcome. METHOD: Information was collected
      from the medical records of 99 patients with schizophrenia consecutively admitted
      to acute care in hospital or by community based 24 h Crisis Teams and
      prospectively studied for 6 months. RESULTS: One-quarter of patients were being
      admitted to acute care within 3 months of their last hospital discharge and only
      34 patients were compliant with their neuroleptic medication 3 months prior to
      the index admission. Twenty-one patients were managed entirely by the Crisis
      Teams, 27 patients received inpatient care only and the remainder (n = 51) had
      both types of acute care. Six months after admission, 42 patients had been
      discharged and did not require further acute care, 29 patients had been re
      admitted at least once and three patients had been transferred to an inpatient
      rehabilitation unit and, therefore, remained in hospital over the entire period.
      Of the remaining 25 patients, one committed suicide 2 months after discharge and
      the other patients were not contactable by Community Mental Health Teams at the 2
      and/or 6 month follow up. CONCLUSIONS: Some of the factors associated with
      relapse identified in the present study were non-compliance with medication,
      stress, inadequate social support and substance abuse. The poor outcome in
      patients with frequent relapses emphasises the need to reduce the occurrences of
      schizophrenic symptoms to provide a better quality of life. The 25% of patients
      dropping out of care soon after a relapse indicates that more should be done to
      engage these people in long-term treatment programs.

PMID- 10084347
TI  - Familial bipolar disorder: preliminary results from the Otago Familial Bipolar
      Genetic Study.
AB  - OBJECTIVE: This paper outlines the methodologies used, and preliminary
      descriptive data collected, on a cohort of familial bipolar disorder (BPD)
      probands and first-degree relatives taking part in a descriptive and genetic
      study into familial BPD in New Zealand. METHOD: Fifty-five bipolar probands and
      67 first-degree relatives were interviewed using the modified Diagnostic
      Interview for Genetic Studies (DIGS) and Family Interview for Genetic Studies
      (FIGS). Data was also collated from other sources. Blood samples were taken for
      DNA genomic analysis. RESULTS: New Zealand families in which BPD segregates
      proved willing participants in this familial based genetic research. The
      methodologies used were acceptable. High rates of comorbidity were found in
      probands (27.3% met DSM-IV criteria for panic disorder/sub-threshold panic
      disorder; 12.7% for phobic disorder; 1.8% for obsessive-compulsive disorder; 9.1%
      for alcohol-related disorders and 7.3% for an eating disorder) and relatives
      (major depression 34.3%; panic disorder/sub-threshold panic disorder 12.0%;
      phobias 11.9% and alcohol-related disorders 11.9%). The polarity of index BPD
      illness was related to age of onset and frequency of comorbidity. Suicidal
      behaviour was common. CONCLUSIONS: Psychiatric genetic research in New Zealand
      families is highly feasible. Emerging trends in the familial transmission of BPD
      include high rates of comorbidity, illness patterns based on polarity of index
      episode and frequent suicidal behaviour. Such trends will be delineated further
      as numbers accrue, perhaps enabling identification of more homogenous phenotypic
      subgroups than currently produced by diagnostic schemes.

PMID- 10084348
TI  - Deliberate exposure to motor vehicle exhaust gas: the psychosocial profile of
      attempted suicide.
AB  - OBJECTIVE: Deliberate exposure to motor vehicle exhaust gas has become the second
      most commonly used method of suicide in Australia. In an attempt to understand
      the factors contributing to the rise in popularity of this method, the
      psychosocial profiles, factors influencing method choice and circumstances of the
      act of self-harm were examined in a group of survivors. METHOD: A cross-sectional
      cohort study of 30 patients presenting for hyperbaric oxygen treatment having
      survived deliberate exposure to car exhaust gas was undertaken. A structured
      clinical interview was administered together with scales measuring depression,
      hopelessness and suicidal intent. Daily assessment of mental state and cognitive
      function was performed. RESULTS: Factors common to the majority of subjects
      included male gender, age group of 20-50 years, and alcohol abuse. Relationship
      discord was the most common precipitating factor. Reasons given for choice of
      this method included the availability and accessibility of motor vehicles,
      painlessness, awareness that the method was lethal, knowledge of another person's
      successful suicide by this method and awareness of the method through media
      portrayal. Most of the cars used did not have engines fitted with catalytic
      converters, substantially increasing the risk of toxicity. Regret of the attempt,
      denial of further suicidal ideation after the event, and the absence of a suicide
      note were common findings. Most denied excessive time spent planning. The most
      common diagnosis in this group was adjustment disorder with depressed mood.
      Suicide intent scores were not high, inconsistent with the majority of patients
      being aware of the lethality of the method. CONCLUSION: Sociodemographic findings
      resemble those of psychological autopsy studies of subjects completing suicide by
      this method. Survival in this group was due to failure of the method or
      unexpected discovery rather than patient factors. This population described the
      method as highly acceptable and accessible emphasising the urgent need for
      reduction of access to this means of suicide in Australia.

PMID- 10084349
TI  - Length of stay, leave and re-offending by patients from a Queensland security
      patients hospital.
AB  - OBJECTIVE: The release of patients from a security patients hospital has been the
      subject of public controversy. The present study uses empirical data to examine
      the length of stay, leave, and re-offending of patients from a security hospital.
      METHODS: Survival analysis was used to examine factors that may be predictive of
      length of stay and time under restriction, as well as time to first overnight
      leave. Data on re-offending were obtained from a variety of sources and were
      compared with seriousness of index offences. RESULTS: Consistent with
      international research, patients with more serious offences had longer
      hospitalisations. Patients with more serious offences were also hospitalised for
      longer periods before leave was granted. Compared with international studies, re
      offending was in the lower range. CONCLUSIONS: Despite concerns raised in the
      media regarding patient 'dangerousness', time spent in hospital and the granting
      of leave, patients with serious offences were more likely to be hospitalised
      longer, which suggests decision makers do take into account public safety.

PMID- 10084350
TI  - Relationship history and relationship attitudes in gay males and lesbians:
      attachment style and gender differences.
AB  - OBJECTIVE: The objective of the present study was to assess the applicability of
      attachment theory to the relationships of gay males and lesbians, with particular
      emphasis on parental relationships, relationship satisfaction, sexual attitudes
      and 'coming out' as being homosexual. METHODS: Gay males (n = 77) and lesbians (n
      = 100) completed questionnaires assessing attachment style, working models of
      attachment, early relationships with parents and relationship history, status and
      functioning. A comparison sample of heterosexual participants completed measures
      of attachment style and relationship history. RESULTS: Relative frequencies of
      attachment styles were similar for homosexual and heterosexual samples. Contrary
      to previous research using largely heterosexual respondents, no link between
      early parenting and attachment style was found. However, homosexual males
      reported more positive early relationships with mothers than did females.
      Associations of attachment style with working models, relationship variables and
      sexual attitudes largely supported those based on heterosexual samples. Gender
      and attachment style differences were found in reported effects of 'coming out'
      on relationships with parents. CONCLUSIONS: Overall, the results suggest that
      insecure attachment may not be over-represented in gay and lesbian samples, but
      that insecurity is associated with less relationship satisfaction and with
      problems related to the disclosure of sexual orientation. The implications of
      these findings for research and clinical practice are addressed.

PMID- 10084351
TI  - Sport psychiatry.
AB  - OBJECTIVE: The aim of this article is to provide an overview of the literature on
      psychiatry for elite athletes. METHOD: Relevant literature was presented to the
      general psychiatrist. RESULTS: The prevalence of drug misuse, eating disorders
      and brain injury in elite and professional athletes is stressed. The uniquely
      troublesome adverse effects of psychopharmacology in this group of subjects is
      commented upon. CONCLUSIONS: Elite athletes may require competent and informed
      psychiatric opinion and management.

PMID- 10084352
TI  - Religious--sociocultural psychotherapy in patients with anxiety and depression.
AB  - OBJECTIVE: To show the effectiveness of incorporating religious-sociocultural
      components in the management of patients with generalised anxiety disorders and
      major depression who have strong religious and cultural backgrounds as compared
      with a normal psychotherapeutic approach. METHODS: One hundred and three cases of
      anxiety and 100 cases of depression with strong religious and cultural
      backgrounds were randomly assigned to the study or control groups. Both groups
      received standard treatment for their respective illnesses. The study group was
      given additional religious-sociocultural psychotherapy. They were followed for 6
      months and were assessed in a double-blind fashion using the Hamilton Anxiety
      Rating Scale or the Hamilton Depression Rating Scale. RESULTS: Patients receiving
      additional religious-sociocultural psychotherapy responded significantly faster
      than those who received standard treatment. However, the difference became non
      significant at the end of 6 months. CONCLUSIONS: Incorporating a religious and
      sociocultural component in the treatment program rapidly improved anxiety and
      depressive symptoms in patients with strong religious and cultural backgrounds.
      The present study demonstrates a need for more sensitivity to religious
      sociocultural issues in the field of mental health.

PMID- 10084353
TI  - Development of a consumer advocacy program.
AB  - OBJECTIVE: The aim of the present paper was to describe the development of a
      consumer advocacy program within the Eastern Suburbs of Sydney (NSW, Australia).
      METHODS: The program was developed within the context of a research project that
      investigated the effect on outcome of client-focused approaches to community case
      management for clients with schizophrenia and bipolar disorder. RESULTS: While
      the development of the advocacy program was limited by the constraints imposed by
      the research methodology, the study provided the opportunity to delineate the
      process involved and identify key components that need to be incorporated into
      future advocacy programs. CONCLUSIONS: The main guidelines determined were that
      consumer participation in service delivery needs to be flexible, consumer driven,
      have broad-based support, ready access to supervision and debriefing, ongoing
      training and clear job descriptions. Given adequate support, autonomy and
      funding, consumer advocates can provide a much needed resource for their fellow
      consumers.

PMID- 10084354
TI  - Mental health professionals' attire.
AB  - OBJECTIVE: Our aim was to obtain mental health patients' views on psychiatrists'
      and case managers' attire. METHODS: Eighty-six patients treated at a community
      mental health service were surveyed. Various types of commonly worn attire were
      listed. Respondents were asked to choose what they thought was most appropriate
      for their psychiatrist and case manager to wear. RESULTS: Over 50% of respondents
      felt that psychiatrist or case manager dress was not an important issue. However,
      those who felt that it was preferred less formal attire. CONCLUSIONS:
      Psychiatrists and case managers in a community mental health team could consider
      adopting less formal attire. This conclusion is limited by the small sample and
      may be relevant to rural areas only. Further research is needed in urban centres.
      Implications of these findings are discussed.

PMID- 10084355
TI  - Neuroleptic malignant syndrome associated with olanzapine.
AB  - OBJECTIVE: The aim of the present paper is to report a case of Neuroleptic
      Malignant Syndrome (NMS) occurring 2 days after olanzapine was added to the
      treatment regimen of an elderly patient with Schizoaffective Disorder. The
      patient had a previous history of NMS associated with risperidone. CLINICAL
      PICTURE: Two days after commencement of olanzapine, the patient presented in a
      stuporous state with dysarthria and increased muscle tone with cogwheeling. His
      level of consciousness fluctuated over the following 24 h with worsening
      rigidity, the onset of a mild fever, tachycardia and elevated blood pressure.
      Biochemical screening revealed markedly elevated creatine kinase. TREATMENT:
      Olanzapine was ceased and intravenous fluid replacement commenced. Hourly
      physical observations were instigated, as was regular serum monitoring of
      creatine kinase level. OUTCOME: Over the subsequent 48 h, there was gradual
      clinical improvement with resolution of dysarthria, ataxia, rigidity and fever.
      The patient was returned to the psychiatric ward 3 days after his admission to
      the medical ward. CONCLUSIONS: Olanzapine therapy can be associated with NMS. To
      our knowledge, there are no previous reports of this in the literature.

PMID- 10084356
TI  - Journal lotteries.

PMID- 10084357
TI  - Bonsai testing of consumer outcome measures for the National Mental Health
      Strategy.

PMID- 10084358
TI  - Schizophrenia and consuming body waste.

PMID- 10084359
TI  - Ethics of community treatment orders.

PMID- 10084360
TI  - Does clozapine affect smoking rates?

PMID- 10084361
TI  - Consent for electroconvulsive therapy.

PMID- 10084362
TI  - Molecular chemotherapy for breast cancer.
AB  - Gene therapy for breast cancer initially involves local or systemic delivery.
      Local delivery may be intrapleural or via direct injection to lesions. However,
      systemic delivery remains the greatest challenge with targeting, although methods
      using antibodies or growth factor receptor ligands have been demonstrated in
      preclinical models. This review focuses on the next step of using tissue-specific
      promoters such as Muc-1, CEA, PSA, HER-2, Myc, L-plastin and secretory
      leukoproteinase inhibitor promoters. All of these have demonstrated differential
      upregulation in breast cancer and additional specificity may be obtained by using
      physiological stimuli that are more frequently expressed in cancers, such as
      glucose regulated promoters and hypoxia response elements or radiation inducible
      elements. Amongst the later are the EGR-1, p21 and tissue type plaminogen
      activator promoters. Potential therapy genes include the prodrug activation
      system 5-fluorocytosine and other analogues of antimetabolites, but all of these
      need gap junctions to transfer the phosphorylated metabolites. Other approaches
      involving more freely diffusible products include cyclophosphamide, ifosfamide
      and thymidine phosphorylase to activate 5-deoxy-5-fluoruridine to fluorouracil.
      The bystander effect is important both for cell killing and for immunological and
      antivascular effects. Breast cancer is one type of tumour where a major clinical
      research effort is underway using local delivery methods. For prodrug activation
      systems, the use of human enzymes is desirable to prevent an immunological
      response that would eventually eliminate cells producing the prodrug activation
      system. The use of alkylating agents has an advantage over antimetabolites in
      that they are cytotoxic to cycling and noncycling cells, and the cytotoxic
      products can diffuse across cell membranes without the need for gap junctions.
      They also have a much steeper dose response curve than antimetabolites.

PMID- 10084363
TI  - Sleep disorders in the elderly.
AB  - Sleep is important for health and quality of life at all ages, and poor sleep
      interacts with many medical conditions. Somatic and psychiatric diseases, and
      unfavourable habits and life-style factors, increase the propensity to insomnia
      in older persons. As health deteriorates with age, sleep becomes poorer. Heart
      disease and stroke, cancer, painful conditions, breathing disorders and nocturnal
      polyuria syndrome often disturb sleep. Dementia and depression, which are often
      associated with sleep disturbances, are also more prevalent in the elderly.
      Moreover, true age-related sleep deterioration occurs after the age of 75 years.
      Attempts to improve sleep should first and foremost be focused on elimination of
      somatic and psychiatric symptoms as far as possible, and on modification of
      lifestyle factors that may affect sleep quality. For short term treatment,
      hypnotics are appropriate; for longer periods, nonpharmacological methods, for
      example light therapy or behavioural modification techniques, should be
      considered, as many hypnotic drugs are less suitable for long term use. However,
      there are situations when sleep medication must continue for long periods,
      especially in elderly patients with severe diseases and poor quality of life. In
      these patients, careful individualisation of therapy is appropriate.

PMID- 10084364
TI  - Practical aspects of drug treatment in elderly patients with mobility problems.
AB  - Elderly people with impaired mobility frequently experience difficulty with
      medication administration and compliance. Many medications are dispensed in
      packages or in containers which are difficult to access by older people with
      disabilities. Attending a medical centre, activating an inhaler, applying
      eyedrops or opening medication containers can prove major obstacles to medication
      compliance for older people with impaired function. Assessment of each patient's
      ability to physically comply with medication regimens by the physician is
      therefore recommended. Contact with the care giver or support person should also
      be made where appropriate. Compliance aids such as some calendar packages for
      medications, metered dose inhalers (MDIs) or eyedrop aids should be prescribed
      where indicated. Because of their close contact with many elderly patients when
      dispensing, pharmacists can also play an important role in ensuring adherence
      with medication regimens. Some medications may improve mobility as seen in the
      treatment of Parkinson's disease whereas other medications such as phenothiazines
      may impair mobility and contribute to falls. Several drug classes including
      antipsychotics, antidepressants, antihypertensives and benzodiazepines have been
      recognised as having an association with falls and impaired mobility. Multiple
      medications have also been found to be a risk factor in falls. Medications should
      be reviewed regularly and rationalised where possible. If mobility problems or
      unexplained falls are occurring, medications should be closely scrutinized as
      they may be responsible. Where possible, domiciliary visits for older people
      should be undertaken by health professionals as they often provide critical
      information about a patient's functional status, their medication compliance and
      their ability to cope at home. Emphasis must be placed on older people
      maintaining their independence and mobility. This is best achieved through a
      multidisciplinary approach.

PMID- 10084367
TI  - Effect of long-term exercise training on regional myocardial perfusion changes in
      patients with coronary artery disease.
AB  - The cardiac rehabilitation of patients with coronary artery disease (CAD)
      promotes exercise tolerance, improves left ventricular function, and decreases
      the heart rate and systolic blood pressure at the same load intensity. Several
      studies have shown that cardiac rehabilitation improves myocardial perfusion in
      CAD patients. However, the long-term (> or = 1 year) effect of cardiac
      rehabilitation on myocardial perfusion is still controversial. The effect of long
      term exercise training on myocardial perfusion in CAD patients was assessed using
      thallium-201 (201Tl) exercise studies at a baseline (4 months after the onset of
      CAD) and at a 1-year or more follow-up in 58 patients with stable CAD. The
      subjects had been divided into a training group (n=35) participating in
      supervised exercise 2 times per week for the follow-up period, and the control
      group (n=23). There was an improvement in the myocardial perfusion on stress
      201Tl scintigraphy in 20 of the 35 (57.1%) trained patients and in 3 of the 23
      (13.0%) of the control patients (p<0.001). The number of 201Tl stress myocardial
      perfusion defect segments was significantly decreased after the cardiac
      rehabilitation training (231 to 153 segments), but showed no change in the
      control group (158 to 156 segments) (p<0.01). In spite of no significant
      differences in the number of involved coronary arteries, it improved (12/17
      patients: 70.6%) more in the patients who had trained for more than 2 years
      compared to the patients who had trained for less than 2 years. The exercise
      tolerance increased in 25 of the 35 training group patients (71.4%), and in only
      3 of the 23 control group patients (13.0%). The peak double products increased
      from 20,131+/-6,010 to 28,370+/-5,600 (p<0.01) in the training group, and showed
      no change in the control group (20,567+/-5,112 to 20,964+/-7,728 (NS)). The
      results indicated that the long-term physical training increased exercise
      tolerance and the double products of CAD patients. In addition, the training
      resulted in improved cardiac perfusion as evidenced by 201Tl scintigraphy. The
      findings suggest that exercise training is an advisable and effective treatment
      for patients with CAD.

PMID- 10084368
TI  - Relationship between brain atrophy estimated by a longitudinal computed
      tomography study and blood pressure control in patients with essential
      hypertension.
AB  - To evaluate the relationship between blood pressure control and the progression
      of brain atrophy in the elderly, patients with essential hypertension and brain
      atrophy were longitudinally evaluated using computerized tomography (CT). The
      study evaluated 48 patients with essential hypertension aged 46-78 years, and 30
      sex- and age-matched normotensive control subjects. The extent of brain atrophy
      as determined by caudate head index (CHI), the inverse cella media index (iCMI),
      and Evans' ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9
      years). The mean annual increases in CHI (deltaCHI), iCMI (delta iCMI), and ER
      (deltaER) were evaluated. Mean blood volume in the common carotid artery (BF) and
      the decrease in BF per year (deltaBF) were also determined. The deltaCHI, delta
      iCMI, and deltaER increased with age in the hypertensive subjects as well as the
      control group across all age groups evaluated. The deltaCHI, delta iCMI, and
      deltaER were significantly greater in the patients with essential hypertension in
      their 50 s as compared with the controls. In patients with essential hypertension
      aged 65 years or older, the deltaCHI, delta iCMI, and deltaER were significantly
      lower in the group in whom the blood pressure was controlled within the range of
      borderline hypertension than the groups in which it was controlled in the range
      of normal or mild hypertension. In the younger patients under the age of 65 with
      essential hypertension, blood pressure control did not affect the deltaCHI, delta
      iCMI, and deltaER. The deltaCHI, delta iCMI, and deltaER were significantly
      correlated with deltaBF in both groups. These findings indicate that control of
      systolic blood pressure within the range of borderline hypertension may delay the
      progression of brain atrophy in elderly patients with essential hypertension.

PMID- 10084366
TI  - The epidemiology of serious adverse drug reactions among the elderly.
AB  - Although the incidence and prevalence of serious adverse drug reactions (ADRs) in
      the elderly cannot be accurately stated, published estimates appear to be
      unchanged since the earliest reports in the 1960s. Whereas heightened awareness
      of the problem may weigh in favour of a reduction in ADR frequency, the dramatic
      increase in the number and availability of therapeutic agents has undoubtedly
      contributed to the observed high proportion of drug-induced morbidity among acute
      geriatric hospital admissions. No single drug or drug class is of particular
      concern since none appears to cause serious morbidity out of proportion with its
      use. Although numerous studies have sought to identify risk factors for ADRs, the
      only truly independent predictor is the absolute number of concurrently used
      medications. However, other studies indicate that there is poor doctor-patient
      agreement regarding a patient's drug regimen, and interventions that aim to
      reduce the incidence of ADRs have failed to demonstrate a positive effect. Thus
      at present the most rational approach would appear to be to establish an accurate
      knowledge of the patients drug regimens: once this is known one can attempt to
      rationally minimise the number of medications without compromising therapeutic
      goals.

PMID- 10084369
TI  - Investigation of the most effective provocation test for patients with coronary
      spastic angina: usefulness of accelerated exercise following hyperventilation.
AB  - This study sought to compare the clinical usefulness of the hyperventilation plus
      cold stress test or the hyperventilation combined with accelerated exercise test
      with other single tests in patients with coronary spastic angina. The study
      examined 24 patients (23 men, mean age 66 years) with angiographically confirmed
      coronary spastic angina and less than 50% stenosis. Moreover, none had
      spontaneous ST segment elevation before the study. Under no medication for at
      least 24 h prior, 4 procedures were performed from 09.00 h to 11.00 h: (i) a
      hyperventilation test for 5 min (HV(5)); (ii) HV(5) combined with a cold stress
      test for the last 2 min (HV(5)+CS(2)); (iii) a treadmill exercise test based on
      Bruce's protocol (TM(3)); and (iv) a treadmill exercise test accelerated at 1 min
      intervals according to Bruce's protocol immediately after HV(5) (HV(5)+TM(1)).
      The rate of appearance of chest pain and ischemia-induced ECG changes due to
      HV(5)+TM(1) were significantly higher than the other 3 tests. HV(5)+CS(2) was not
      superior to HV(5) alone. The incidence of provoked ST segment elevation due to
      HV(5)+TM(1) was higher than with the other 3 procedures. Thus, in patients with
      coronary spastic angina, no spontaneous ST segment elevation and near normal
      coronary arteries, HV(5)+CS(2) was no more useful than HV(5) alone. It is
      recommended that the newly designed HV(5)+TM(1) combination test be used for
      documenting evidence of ischemia in patients with coronary spastic angina, low
      disease activity and near normal coronary arteries.

PMID- 10084370
TI  - Percutaneous transluminal coronary angioplasty, alone or in combination with
      urokinase therapy, during acute myocardial infarction.
AB  - To investigate the effect of pre-treatment of a thrombus with a low dose of
      urokinase on establishing patency in a persistent infarct-related artery (IRA)
      during direct percutaneous coronary angioplasty (PTCA), the frequency of acute
      restenosis during direct PTCA, alone, or in combination with the intracoronary
      administration of urokinase, was examined in a consecutive nonrandomized series
      of patients with acute myocardial infarction (AMI). Two hundred and seventy-two
      successful PTCA patients (residual stenosis <50%) were divided into 2 groups: 88
      patients received pre-treatment with intracoronary urokinase following PTCA
      (combination group); 184 received only direct PTCA without thrombolytic therapy
      (PTCA group). In the present study, after achievement of a residual stenosis of
      less than 50%, IRA was visualized every 15 min to assess the frequency of acute
      restenosis, which was defined as an acute progression of IRA with more than 75%
      restenosis after initially successful PTCA. In the patients with a large coronary
      thrombus, the frequency (times) of acute restenosis was significantly lower in
      the combination group than in the PTCA group (0.98+/-0.19 vs 2.92+/-0.32,
      p<0.0001). On the other hand, in the patients with a small coronary thrombus, the
      frequency of acute restenosis showed no difference in either group. The present
      study indicates that in patients with AMI, PTCA combined with pre-treatment of a
      low dose of urokinase is much more effective than PTCA alone, especially for
      those patients who have a large coronary thrombus.

PMID- 10084365
TI  - The role of iron in neurodegeneration: prospects for pharmacotherapy of
      Parkinson's disease.
AB  - Although the aetiology of Parkinson's disease (PD) and related neurodegenerative
      disorders is still unknown, recent evidence from human and experimental animal
      models suggests that a misregulation of iron metabolism, iron-induced oxidative
      stress and free radical formation are major pathogenic factors. These factors
      trigger a cascade of deleterious events leading to neuronal death and the ensuing
      biochemical disturbances of clinical relevance. A review of the available data in
      PD provides the following evidence in support of this hypothesis: (i) an increase
      of iron in the brain, which in PD selectively involves neuromelanin in substantia
      nigra (SN) neurons; (ii) decreased availability of glutathione (GSH) and other
      antioxidant substances; (iii) increase of lipid peroxidation products and
      reactive oxygen (O2)species (ROS); and (iv) impaired mitochondrial electron
      transport mechanisms. Most of these changes appear to be closely related to
      interactions between iron and neuromelanin, which result in accumulation of iron
      and a continuous production of cytotoxic species leading to neuronal death. Some
      of these findings have been reproduced in animal models using 6-hydroxydopamine,
      N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), iron loading and beta
      carbolines, although none of them is an accurate model for PD in humans. Although
      it is not clear whether iron accumulation and oxidative stress are the initial
      events causing cell death or consequences of the disease process, therapeutic
      efforts aimed at preventing or at least delaying disease progression by reducing
      the overload of iron and generation of ROS may be beneficial in PD and related
      neurodegenerative disorders. Current pharmacotherapy of PD, in addition to
      symptomatic levodopa treatment, includes 'neuroprotective' strategies with
      dopamine agonists, monoamine oxidase-B inhibitors (MAO-B), glutamate antagonists,
      catechol O-methyltransferase inhibitors and other antioxidants or free radical
      scavengers. In the future, these agents could be used in combination with, or
      partly replaced by, iron chelators and lazaroids that prevent iron-induced
      generation of deleterious substances. Although experimental and preclinical data
      suggest the therapeutic potential of these drugs, their clinical applicability
      will be a major challenge for future research.

PMID- 10084371
TI  - Early occurrence of respiratory muscle deoxygenation assessed by near-infrared
      spectroscopy during leg exercise in patients with chronic heart failure.
AB  - The mechanisms of respiratory muscle deoxygenation during incremental leg
      exercise with expired gas analysis were investigated in 29 patients with chronic
      heart failure and 21 normal subjects. The deoxygenation and blood volume of the
      respiratory muscle and exercising leg muscle were assessed by near-infrared
      spectroscopy (NIRS). To evaluate the influence of the leg exercise on the blood
      volume of the respiratory muscle, 10 normal subjects also underwent a
      hyperventilation test with NIRS. The respiratory muscle deoxygenation point
      (RDP), at which oxygenated hemoglobin starts to decrease, was observed in both
      groups during exercise. The oxygen consumption (VO2) and the minute ventilation
      at the RDP in the patients was lower (p<0.01). At the same VO2, the respiratory
      rate was higher in patients (p<0.01). During exercise, the blood volume of the
      leg muscle increased, while that of the respiratory muscle decreased. During a
      hyperventilation test, the minute ventilation was higher than that of the RDP
      during exercise, the blood volume of the respiratory muscle did not decrease, and
      the RDP was not detectable. In conclusion, a limited ability to increase
      perfusion of respiratory muscles during exercise combined with the greater work
      of breathing results in early respiratory muscle deoxygenation in patients with
      chronic heart failure.

PMID- 10084372
TI  - Determinants of exercise-induced ST-segment displacement in the aVL lead in
      patients with known or suspected coronary artery disease.
AB  - Although the aVL lead in exercise electrocardiography is reported to be helpful
      in identifying a significant narrowing of the left anterior descending coronary
      artery (LAD), its role in exercise testing has not been fully evaluated.
      Accordingly, 821 patients who underwent both standard exercise testing and
      coronary angiography were evaluated. In patients with aVL lead ST elevation, the
      incidence of a significant narrowing of the LAD (124/165 vs 348/656; p<0.001) was
      higher than in those without. Multiple logistic regression analysis revealed that
      the 2 most important variables that correlated with aVL lead ST elevation were a
      greater number of leads with ST depression in the inferior leads and a smaller
      amplitude of R wave in the aVL lead. In contrast, variables correlating with aVL
      lead ST depression in the majority of cases were a greater number of leads with
      ST depression in all leads and the presence of inferior lead ST elevation. The
      results of this study indicate that although aVL lead ST elevation could be a
      marker for LAD narrowing, more important factors such as inferior lead ST-segment
      depression and the R-wave amplitude of the aVL lead should be taken into
      consideration. In contrast, ST depression in the aVL lead mostly represents
      exercise-induced myocardial ischemia of greater extent and severity.

PMID- 10084373
TI  - Effects of nicorandil on aortic input impedance: a comparative study with
      nitroglycerin.
AB  - A study of aortic input impedance was performed to evaluate the effects of
      nicorandil on the systemic circulation, and the effects were compared with those
      of nitroglycerin. Sixteen patients with coronary artery disease were divided into
      2 age-matched groups. Aortic input impedance was obtained from Fourier analysis
      of aortic pressure and flow signals at baseline conditions, after intravenous
      administration of either 4 mg (Group 1) or 8 mg (Group 2) nicorandil, and 20 min
      after 0.3 mg sublingual nitroglycerin. In Group 1, the first harmonic impedance
      modulus (Z1, 304+/-140 dyne x s x cm(-5)) and the average of the first to third
      harmonics (Z1-3, 207+/-99 dyne x s x cm(-5)), indices of wave reflection,
      significantly decreased (24.4% (p<0.05) and 24.7% (p<0.01), respectively) after
      nicorandil, and 41.3% (p<0.01) and 33.9% (p<0.01) after nitroglycerin. The
      effects between the 2 vasodilators were not significantly different. In Group 2,
      Z1 and Z1-3 (275+/-138 and 196+/-93 dyne x s x cm(-5), respectively) also
      decreased after administration of nicorandil (28.4% (p<0.01) and 35.9% (p<0.01),
      respectively), and after administration of nitroglycerin (23.9% (p<0.01) and
      28.7% (p<0.01), respectively), without any significant difference between the 2
      drugs. Characteristic impedance and total peripheral resistance (R) in both
      groups remained unchanged except for R after 8 mg nicorandil (from 1830+/-415 to
      1433+/-428 dyne x s x cm(-5); p<0.01). Like nitroglycerin, both doses of
      nicorandil reduced wave reflection. The reduction in R after 8 mg nicorandil is
      related to decreased tone in the resistance arteries, probably due to potassium
      channel opener effects.

PMID- 10084374
TI  - Effects of phosphodiesterase inhibitors after coronary artery bypass grafting.
AB  - The aim of this study was to estimate the postoperative effects of
      phosphodiesterase (PDE) inhibitors (milrinone and olprinone) after coronary
      artery bypass grafting (CABG). To prevent hypotension caused by the PDE
      inhibitors, low dose of catecholamines were used concomitantly. A total of 34
      elective CABG cases were tested. In 12 cases, 0.25 microg kg(-1) min(-1) of
      milrinone, 3 microg kg(-1) min(-1) of dobutamine (DOB) and dopamine (DOA) were
      used concomitantly (Group-M). In another 10 patients, 0.1 microg kg(-1) min(-1)
      of olprinone and the same doses of the catecholamines were infused (Group-O). As
      a control, the same doses of DOA and DOB only were administered in 12 patients
      (Group-C). When the pump flow of the cardiopulmonary bypass (CPB) decreased to
      half, these drugs were given in all groups. Hemodynamics were recorded before
      CPB, just after the operation, and 3, 6, 12, 24, 48 and 72 h after the operation.
      Both milrinone and olprinone increased the cardiac index and decreased systemic
      vascular resistance to almost the same degree. Olprinone decreased mean aortic
      and pulmonary artery pressures, and also significantly reduced the preload of
      both right and left heart compared with milrinone. Significant hypotension was
      not detected due to the concomitant usage of low-dose catecholamines. This
      concomitant usage of PDE inhibitors and catecholamines allowed easy weaning from
      CPB, demonstrating excellent hemodynamics after CABG. Good oxygen demand and
      supply balance were maintained in peripheral tissue. These results suggest that
      these new PDE inhibitors may be effective not only for weaning from CPB but also
      for post-cardiotomy cardiogenic shock.

PMID- 10084375
TI  - A calcium antagonist protects against doxorubicin-induced impairment of calcium
      handling in neonatal rat cardiac myocytes.
AB  - The effects of doxorubicin (DOX) on intracellular calcium transients and the
      cardioprotective effects of a calcium antagonist on DOX-induced impairment of
      calcium handling were examined in neonatal rat cultured cardiac myocytes.
      Cultured cardiac myocytes isolated from neonatal Wistar-Kyoto rats were treated
      with DOX for 24 h. Field-stimulated calcium transients in single myocytes were
      measured in the presence or absence of isoproterenol using fura-2/AM. Calcium
      transients were also measured after the addition of DOX to myocytes pretreated
      with a calcium antagonist, benidipine. DOX reduced the amplitude, maximum
      velocity of increase and decrease of calcium transients and prolonged the time
      course of calcium transients and impaired the beta-adrenoceptor responsiveness of
      calcium transients in a concentration-dependent manner. The DOX-induced
      impairment of calcium transients and beta-adrenoceptor responsiveness was
      improved by 10(-8) mol/L of benidipine. However, these improvements decreased
      with increasing concentrations of benidipine. DOX impaired both the mobilization
      and removal of intracellular calcium ions in contraction-relaxation cycles and
      the response of calcium transients to beta-adrenoceptor stimulation. Appropriate
      concentration of benidipine ameliorated DOX-induced impairment of calcium
      dynamics, suggesting that benidipine, a long-acting calcium antagonist, has
      potential clinical usefulness on DOX-induced abnormal calcium handling.

PMID- 10084376
TI  - Rapid progression of cardiomyopathy in mitochondrial diabetes.
AB  - Cardiac involvement and its clinical course in a diabetic patient with a
      mitochondrial tRNA(Leu)(UUR) mutation at position 3243 is reported in a 54-year
      old man with no history of hypertension. At age 46, an electrocardiogram showed
      just T wave abnormalities. At age 49, it fulfilled SV1 + RV5 or 6>35 mm with
      strain pattern. At age 52, echocardiography revealed definite left ventricular
      (LV) hypertrophy, and abnormally increased mitochondria were shown in biopsied
      endomyocardial specimens. He was diagnosed as having developed hypertrophic
      cardiomyopathy associated with the mutation. However, at age 54, SV1 and RV5,6
      voltages were decreased, and echocardiography showed diffuse decreased LV wall
      motion and LV dilatation. Because he had mitochondrial diabetes, the patient's
      heart rapidly developed hypertrophic cardiomyopathy, and then it seemed to be
      changing to a dilated LV with systolic dysfunction. Rapid progression of
      cardiomyopathy can occur in mitochondrial diabetes.

PMID- 10084377
TI  - Primary percutaneous transluminal coronary angioplasty performed for acute
      myocardial infarction in a patient with idiopathic thrombocytopenic purpura.
AB  - A 72-year-old female with idiopathic thrombocytopenic purpura (ITP) complained of
      severe chest pain. Electrocardiography showed ST-segment depression and negative
      T wave in I, aVL and V4-6. Following a diagnosis of acute myocardial infarction
      (AMI), urgent coronary angiography revealed 99% organic stenosis with delayed
      flow in the proximal segment and 50% in the middle segment of the left anterior
      descending artery (LAD). Subsequently, percutaneous transluminal coronary
      angioplasty (PTCA) for the stenosis in the proximal LAD was performed. In the
      coronary care unit, her blood pressure dropped. Hematomas around the puncture
      sites were observed and the platelet count was 28,000/mm3. After transfusion,
      electrocardiography revealed ST-segment elevation in I, aVL and V1-6. Urgent
      recatheterization disclosed total occlusion in the middle segment of the LAD.
      Subsequently, PTCA was performed successfully. Then, intravenous immunoglobulin
      increased the platelet count and the bleeding tendency disappeared. A case of AMI
      with ITP is rare. The present case suggests that primary PTCA can be a useful
      therapeutic strategy, but careful attention must be paid to hemostasis and to
      managing the platelet count.

PMID- 10084378
TI  - A patient with hypertrophic cardiomyopathy accompanied by right ventricular
      dilation of unknown cause.
AB  - Hypertrophic cardiomyopathy (HCM) is a disease characterized by an unknown cause
      of hypertrophy in the left or right ventricle. The dilated phase of HCM shows
      disease conditions resembling dilated cardiomyopathy, such as ventricular
      dilation, thin ventricular wall, and reduction of the ejection fraction. A
      patient presented with left ventricular concentric hypertrophy accompanied by
      right ventricular dilatation of unknown cause. Right ventricular endomyocardial
      biopsy specimens showed characteristic myocardial disarray. Therefore, there is
      the possibility that the patient had right and left ventricular HCM in the
      process toward the dilated phase, in which dilatation first occurred in the right
      ventricle.

PMID- 10084379
TI  - A case of eosinophilic myocarditis complicated by Kimura's disease (eosinophilic
      hyperplastic lymphogranuloma) and erythroderma.
AB  - This report describes a patient with eosinophilic myocarditis complicated by
      Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma. A
      50-year-old man presented with a complaint of precordial pain. However, the only
      abnormal finding on examinatioin was eosinophilia (1617 eosinophils/microl).
      Three years later, the patient developed chronic eczema, and was diagnosed with
      erythroderma posteczematosa. One year later, a tumor was detected in the right
      auricule, and a diagnosis of Kimura's disease was made, based on the biopsy
      findings. The patient developed progressive dyspnea 6 months later and was found
      to have cardiomegaly and a depressed left ventricular ejection fraction (17%). A
      diagnosis of eosinophilic myocarditis was made based on the results of a right
      ventricular endomyocardial biopsy. The eosinophilic myocarditis and erythrodrema
      were treated with steroids with improvement of both the eosinophilia and left
      ventricular function.

PMID- 10084380
TI  - Decreased left ventricular filling pressure 8 months after corrective surgery in
      a 55-year-old man with tetralogy of Fallot: adaptation for increased preload.
AB  - A 55-year-old man with tetralogy of Fallot underwent corrective surgery. Left
      ventricular filling pressure increased markedly with increased left ventricular
      volume one month after surgery, then decreased over the next 7 months, presumably
      due to increased left ventricular compliance.

PMID- 10084381
TI  - Profiles of aprindine, cibenzoline, pilsicainide and pirmenol in the framework of
      the Sicilian Gambit. The Guideline Committee for Clinical Use of Antiarrhythmic
      Drugs in Japan (Working Group of Arrhythmias of the Japanese Society of
      Electrocardiology).
AB  - The Vaughan Williams classification has been used widely by clinicians,
      cardiologists and researchers engaged in antiarrhythmic drug development and
      testing in many countries throughout the world since its initial proposal in the
      early 1970s. However, a major criticism of the Vaughan Williams system arose from
      the extent to which the categorization of drugs into classes I-IV led to
      oversimplified views of both shared and divergent actions. The Sicilian Gambit
      proposed a two-dimensional tabular framework for display of drug actions to solve
      these problems. From April to December 1996, members of the Guideline Committee
      met to discuss pharmacologic profiles of 4 antiarrhythmic drugs (aprindine,
      cibenzoline, pilsicainide, and pirmenol) that were not included in the original
      spreadsheet but are used widely in clinical practice in Japan. The discussion
      aimed to fit the drug profiles into the Gambit framework based on all the
      important literature published to date regarding the actions of the 4 drugs. This
      report is a summary of that deliberation.

PMID- 10084382
TI  - Does coronary artery morphology predict favorable results of intracoronary
      thrombolysis in patients with unstable angina pectoris?
AB  - The efficacy of intracoronary thrombolysis (ICT) for unstable angina pectoris
      (UAP) has been limited, despite the similar pathogenesis between UAP and acute
      myocardial infarction. To ascertain the subset of UAP suitable for ICT, the
      clinical responses to ICT were assessed in patients with UAP. Eighty-2 patients
      with medically refractory angina were divided into 2 groups according to the
      coronary artery morphology of the culprit lesion before ICT: (1) lesions with
      acute cut off and/or filling defects (AC) and (2) lesions with a tapered shape
      (TA). The TIMI flow grade was determined from coronary angiograms before and
      immediately after ICT. The diameter stenosis (%DS) and minimal lumen diameter
      (MLD) of the culprit lesion were determined using quantitative coronary
      angiographic analysis before and immediately after ICT. In addition, inhospital
      cardiac event rates including urgent/emergency coronary angioplasty or bypass
      surgery, nonfatal myocardial infarction or cardiac death were compared between
      the 2 groups. Multivariate logistic regression analysis was performed using 13
      clinical factors contributing to successful ICT. The results showed that all 3
      coronary angiographic parameters (TIMI flow, %DS, and MLD) significantly improved
      in the AC group (p<0.01, p<0.01 and p<0.05, respectively), whereas none of these
      parameters improved in the TA group. The inhospital cardiac event rate after ICT
      was significantly higher in the TA group (76%) than in the AC group (48%;
      p=0.016). Odds ratio predicting successful ICT was 7.09 (p<0.01) for the AC
      lesion, and 2.54 (p<0.01) for new angina. In conclusion the AC lesions are more
      commonly associated with coronary thrombosis that responds to ICT than are the TA
      lesions. Thus, the coronary angiographic morphology may be an important predictor
      for a successful ICT in patients with medically refractory UAP.

PMID- 10084383
TI  - Levels of soluble cell adhesion molecules in patients with angiographically
      defined coronary atherosclerosis.
AB  - Adhesion molecules on the endothelial cell membrane play an important role in the
      pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion
      molecules are reportedly elevated in patients with peripheral artery vessel
      disease and in patients with an atherosclerotic aorta. The present study
      investigated the association of serum levels of soluble vascular cell adhesion
      molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and
      soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent
      of coronary atherosclerosis, and examined the influence of serum levels of
      lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9)
      and without (controls, n=40, M/F:25/15) angiographically proven coronary
      atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least
      squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/
      17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml,
      ns) in patients with coronary atherosclerosis were not different from those in
      controls, as assessed by an analysis of covariance. After also adjusting for body
      mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic
      function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD
      was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also
      not related to the extent of coronary atherosclerosis as judged by the number of
      stenosed vessels. However, inverse (p<0.05) relationships were observed between
      sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing
      apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A
      II), and between sP-selectin and lipoprotein containing only apo A-I. In
      conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not
      related to CHD or the extent of coronary atherosclerosis, but were inversely
      related to serum levels of high-density lipoprotein-related lipoproteins.

PMID- 10084384
TI  - Detection of abnormal high-frequency components in the QRS complex by the wavelet
      transform in patients with idiopathic dilated cardiomyopathy.
AB  - In order to investigate whether increased fine, fractionated signals within the
      QRS complex can detect arrhythmogenic substrates and how these fine signals link
      with ventricular mechanical dysfunction, wavelet analysis was performed on
      averaged QRS complexes obtained from the left precordial lead in 26 patients with
      idiopatic dilated cardiomyopathy (IDCM) and in 12 normal subjects. The number of
      local maxima and the duration of the wavelet transform were significantly greater
      in patients with IDCM than in normal subjects; the number at 100 Hz was 8.8+/-3.1
      vs 6.0+/-1.1 (p<0.01), and the duration at 100Hz was 93+/-15 vs 75+/-7ms
      (p<0.01). Both of these indices were greater in the patients with than in those
      without late potentials, repetitive ventricular premature beats or cardiac death.
      In addition, significant inverse curvilinear relationships were observed between
      the left ventricular ejection fraction and both the number of local maxima and
      the duration of the wavelet transform. In conclusion, fine fragmented signals in
      the QRS complex detected by wavelet analysis would be an important marker for
      potentially arrhythmogenic substrates and seemed to progress in parallel with
      left ventricular mechanical dysfunction in IDCM.

PMID- 10084385
TI  - Long-term prognosis in achieving a 'stent'like' result from balloon angioplasty:
      8 years' clinical outcome.
AB  - This study evaluated the long-term prognosis of optimal 'stent-like' results,
      suboptimal results and failure of balloon angioplasty. The clinical data of 108
      patients were examined during 8 years following balloon angioplasty. Based on the
      angiographic results, the patients were divided into 3 groups: Group A (n=59),
      <25% residual stenosis (ie, optimal stent-like result); Group B (n=43), 26-50%
      residual stenosis or large dissection (ie, suboptimal result); and Group C (n=6),
      >50% residual stenosis or stenosis could not be crossed (ie, failed angioplasty).
      Restenosis occurred in 20 of 43 patients (46.5%) in Group B, but only in 18 of 59
      patients (30.4%) in Group A. Achieving stent-like results following balloon
      angioplasty significantly reduced the incidence of restenosis. Kaplan-Meier
      curves at 8 years demonstrated a survival rate without serious cardiac events of
      83% in patients with stent-like results compared with 58% in those with
      suboptimal results and 17% in those with failed balloon angioplasty. In
      conclusion, the major finding of this study is that achieving stent-like results
      following balloon angioplasty reduces the incidence of restenosis, and 8-year
      survival without serious cardiac events after balloon angioplasty is
      significantly better in patients who have a stent-like result.

PMID- 10084386
TI  - Sudden death in the general population in Okinawa: incidence and causes of death.
AB  - Sudden unexpected death is generally considered to be caused by acute myocardial
      infarction and/or arrhythmia. To document the incidence and causes of sudden
      death in Japan, where the incidence of myocardial infarction is low, the present
      study examined death certificates, hospital records, the forensic medical
      records, and the police records of residents of the southern part of Okinawa
      island who died at the age of 20-74 years during a 3-year period from January 1,
      1992 to December 31, 1994. Sudden death was defined as death within 24 h from the
      onset of unexpected symptoms. The study documented 126 (87 men and 39 women)
      sudden deaths. The crude incidence rate was 0.37/1,000 person per year (0.51 in
      men and 0.23 in women). According to the death certificates, 78 cases died of
      heart diseases. However, the cause of death could be determined by examination of
      all available records in only 64 cases: myocardial infarction in 10, non-ischemic
      heart diseases in 13, and stroke in 23 cases. Even when the analysis was limited
      to the cases who died within 1 h from the onset of symptoms, heart disease was
      the cause of death in only 22% of the cases while the cause of death could not be
      determined in 53% of the cases. Only 13% of those diagnosed as heart diseases on
      the death certificate were verified. The agreement rate between the diagnosis
      reached by the re-evaluation of the records and that on the death certificate was
      82% for stroke and 33% for other diseases. In Okinawa, Japan, the frequencies of
      heart disease and stroke as the cause of sudden death may be similar. Except for
      stroke, the diagnosis appearing on the death certificate has substantial
      inaccuracy.

PMID- 10084387
TI  - Dynamic effects of intravenous procainamide infusion on the electrophysiological
      properties during atrial fibrillation.
AB  - Although the mechanism of atrial fibrillation (AF) is still controversial,
      multiple wandering reentry is considered the primary mechanism in most AF. It has
      been suggested that prolongation of the wavelength would make it impossible for
      the reentry to continue and would lead to the termination of the AF. In the
      present study a dynamic fluctuation in the electrophysiological properties was
      observed with procainamide infusion during AF. In 12 patients, both the local
      electrogram and monophasic action potentials (MAP) during AF were recorded from
      the right atrium before, during and after infusion of procainamide (10 mg/kg).
      The minimum AF cyclelength (CLmin), MAP duration at 90% repolarization (MAPD90)
      and widths of the intraatrial potentials (WAP) were measured with custom-made
      computer software. The conduction velocity index (CVI) was determined from the
      WAP. The wavelength index (WLI=CVIxCLmin) and postrepolarization refractoriness
      (PRR= CLmin-MAPD90) were calculated. In 6 patients, AF was terminated by
      procainamide infusion (group A), but not in the other 6 patients (group B). Group
      A patients showed a biphasic change in the parameters following procainamide
      infusion. In phase I, the CLmin, MAPD90 and PRR increased, while the CVI
      decreased, and the WLI remained unchanged. In phase II, the PRR, CVI and WLI
      increased and the AF was terminated. No restoration of the CVI nor increase in
      the WLI were observed in group B. The biphasic fluctuation in the CVI and the
      remarkable increase of the PRR and WLI were observed before termination of AF by
      procainamide infusion.

PMID- 10084388
TI  - Differential diagnosis of left ventricular mural thrombi by myocardial contrast
      echocardiography: a preliminary study.
AB  - Two-dimensional echocardiography has become the procedure of choice to diagnose
      left ventricular mural thrombi. However, small or flat thrombi may be difficult
      to distinguish from myocardium. The spatial distribution of the ventricular
      myocardial blood flow can be imaged with myocardial contrast echocardiography
      (MCE). The authors presumed that the absence of arterial supply to a fresh
      thrombus may allow MCE to distinguish between thrombus and myocardium. In the 2
      cases presented here, MCE was performed with the same technique as that used for
      the purpose of visualization of myocardial perfusion; as a result, an apical
      mural thrombus, indistinct from myocardium before MCE, was visualized as a
      contrast defect during imaging. Conversely, myocardium that mimicked a thrombus
      was imaged by MCE as a contrast-opacified area. These findings suggest that MCE
      after reperfusion therapy is useful to distinguish mural thrombi from myocardium.

PMID- 10084389
TI  - Low serum cholesterol as a risk factor for hemorrhagic stroke in men: a community
      based mass screening in Okinawa, Japan.
AB  - The relation between the level of total serum cholesterol and stroke is
      controversial. The relation between serum total cholesterol and subtypes of
      stroke was examined in the participants of a community-based mass screening
      program in Okinawa, Japan. A total of 38,053 subjects, whose serum level of
      cholesterol had been determined during a mass screening carried out in 1983, were
      examined to see whether they had experienced stroke during a 3-year period from
      1988 to 1991. Of them, 315 subjects aged 33-93 years (174 men, 141 women) had had
      a stroke during that period. The types of stroke were cerebral infarction in 164,
      cerebral hemorrhage in 111, subarachnoid hemorrhage in 19, and others in 21. In
      men, the odds ratio of cerebral hemorrhage was 0.71 (95% confidence interval,
      0.55-0.95), and the odds ratio of cerebral hemorrhage associated with serum level
      of cholesterol < or =167 mg/dl, 168-191 mg/dl, 192-217mg/dl, and > or =218mg/dl
      were 1.00 (reference), 0.70 (0.38-1.30), 0.77 (0.55-1.08), 0.73 (0.56-0.96),
      respectively. Lower serum cholesterol was an independent predictor of cerebral
      hemorrhage in men.

PMID- 10084390
TI  - Isolated primary chylopericardium.
AB  - A 16-year-old man was found to have an enlarged cardiac silhouette. Primary
      chylopericardium was diagnosed when pericardiocentesis yielded the characteristic
      milky-white fluid. The thoracic duct was easily identified by giving milk and
      butter and an injection of ethylene blue immediately before the operation.
      Intraoperative thoracic ductography showed no abnormal findings. Mass ligation of
      the thoracic duct above the diaphragm and partial pericardiectomy were
      successfully performed through a right thoracotomy approach. In addition, many of
      the lymphatics were ligated above the diaphragm. The right thoracotomy approach
      was a useful method for resection and ligation of the thoracic duct just above
      the diaphragm. Follow-up showed no accumulation of pericardial fluid or pleural
      effusion.

PMID- 10084391
TI  - Regional left ventricular dysfunction in a patient with severe prolonged anemia.
AB  - A 47-year-old woman with severe prolonged anemia developed heart failure. After
      treatment of the heart failure and anemia, she showed regional dysfunction of the
      left ventricular wall and myocardial fatty acid metabolism was disturbed in these
      sites. Coronary arteriography showed normal images. It took about 4 months to
      recover both left ventricular wall motion and fatty acid metabolism. Prolonged
      decrease of oxygen supply to the myocardium, which is caused by severe prolonged
      anemia, seemed to affect the myocardial function in this case, which could be
      another model of anemia-related myocardial dysfunction.

PMID- 10084392
TI  - Residual cardiomyocytes and scintigraphic findings in advanced coronary artery
      disease: correlation with technetium-99m-tetrofosmin and thallium-201 single
      photon emission computed tomography.
AB  - A 68-year-old man suffering from chronic heart failure due to coronary artery
      disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201
      (201Tl) with reinjection studies, but died thereafter. The heart was removed and
      sectioned into short-axis slices and examined by gross and microscopic pathologic
      methods. A close correlation between the amount of residual cardiomyocytes and
      the level of regional tracer activity in the left ventricular wall was obtained
      for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images.
      The correlation coefficients were r=0.901 for the 201Tl redistribution images,
      r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc
      tetrofosmin images. This case report provides further evidence of the validity of
      SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.

PMID- 10084393
TI  - Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of
      a patient with progressive systemic sclerosis.
AB  - A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to
      hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse
      hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone,
      heparin, and diuretics were administered, without benefit. Anemia,
      thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart
      failure on the 14th hospital day. Immunohistochemical study of the myocardial
      tissue showed mild to moderate cell infiltration, mainly consisting of natural
      killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper
      cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and
      NK cells, indicating that these cells were activated killer cells. Furthermore,
      human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as
      well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not
      to be expressed in cardiac myocytes under normal conditions, were moderately to
      strongly expressed in cardiac myocytes. There was no detectable level of
      enterovirus genomes in the polymerase chain reaction products from the myocardial
      tissue of this patient. These findings strongly suggest that the infiltrating
      killer cells recognized cardiac myocytes as target cells and directly damaged
      them by releasing perforin. Enhanced expression of these antigens may have played
      an important role in the activation and cytotoxicity of the infiltrating killer
      cells. Absence of enterovirus genomes in the myocardial tissue may suggest that
      this autoimmune process is primarily induced by PSS.

PMID- 10084394
TI  - The role of integrins in osteoclast function.

PMID- 10084395
TI  - Cartilaginous differentiation in the joint capsule.
AB  - The proliferation and differentiation of cells are greatly influenced by their
      environment. Many growth factors and cytokines are reported to be environmental
      factors that affect the proliferation and differentiation of cells. Mechanical
      stress is also considered to influence these physiological reactions. The joint
      capsule, which is a part of the joint tissue, plays a very important role in the
      stability of the joint and in maintaining the intracapsular phenomenon. In
      patients with dislocated hip arthropathy, this capsule is involved in the
      weightbearing function by forming a sliding surface between the capsule and the
      femoral head articular cartilage. The surface of the tissue macroscopically shows
      cartilaginous change, which indicates cartilaginous differentiation caused by
      mechanical stress. We examined the cartilage-specific proteoglycan component,
      which is composed of cartilaginou matrix at the differentiation site. We
      investigated proteoglycan production, molecular size, and the gene expression of
      cartilaginous substrate. At the inner layer of the weightbearing area of the
      joint capsule, proteoglycan production was significantly higher than that of
      other noncartilaginous tissue. We also identified the gene expression of
      cartilaginous proteoglycan using the reverse transcription polymerase chain
      reaction (RT-PCR) method.

PMID- 10084396
TI  - Local effects of transforming growth factor-beta1 on rat calvaria: changes
      depending on the dose and the injection site.
AB  - Transforming growth factor-beta1 (TGF-beta1) has opposite effects on osteoblastic
      cells in vitro, namely an inhibitory or stimulatory effect on cell
      differentiation. Because these effects are dependent on TGF-beta1 concentration
      or culture condition, we investigated whether the in vivo effects of TGF-beta1 on
      bone formation in infant rat calvaria were affected by the dose or the injection
      site. Human platelet-derived TGF-beta1 was injected subcutaneously onto the
      periosteal surface of parietal bone of 4-week-old rats at doses of 5 or
      20ng/100microl per animal for 14 days, and the local effect on bone formation was
      examined by bone histomorphometry. TGF-beta1 treatment for 7 days decreased the
      mineral apposition rate, bone formation rate, and elongated mineralization lag
      time at the injection site. This change became more prominent when treatment
      continued for 14 days. These changes were restricted to the TGF-beta1-exposed
      area. Multiple subcutaneous injections of a relatively high dose (200ng/100microl
      per animal) of TGF-beta1 induced woven bone formation, in addition to marked
      inhibition of bone formation rate and prolongation of mineralization lag time. On
      the other hand, direct exposure of TGF-beta1 in the subperiosteal layer induced
      woven bone with periosteal cell proliferation even at a single injection of a low
      dose (5 or 50ng/25 microl) of TGF-beta1. In conclusion, the in vivo effects of
      TGF-beta1 on bone formation varied depending on its concentration and injection
      site. Also, subcutaneous injection of relatively low doses of TGF-beta1 inhibited
      local lamellar bone formation.

PMID- 10084397
TI  - Skeletal effects of constant and terminated use of risedronate on cortical bone
      in ovariectomized rats.
AB  - To study the skeletal effects of continual and terminated use of risedronate
      treatment on cortical bone in ovariectomized (Ovx) rats, we used risedronate
      (Ris), 5 microg x kg(-1), by subcutaneous injections, twice per week. The middle
      part of the tibial shafts (Tx) were processed undecalcified for quantitive bone
      histomorphometry. Cortical bone and the marrow areas of the tibial shaft did not
      change in either sham-Ovx or Ovx rats during the 150-day experimental period.
      Continued administration of Ris for 150 days decreased the marrow area and
      increased the percentage of cortical area compared with the matching sham and Ovx
      group. A decrease in bone formation indices in both periosteal and endocortical
      surfaces of Tx in sham-operated rats between the age of 5 and 8 months was seen.
      Ovariectomy increased the percentage of labeled perimeter in the periosteal area,
      and markedly increased the percentage of eroded perimeter in the endocortical
      surface compared with sham control groups in 81 and 150 days. Bone formation
      indices of Ris treatment were increased in periosteal surfaces, and percentages
      of eroded perimeter were decreased more in endocortical surfaces in 150 days than
      in the matching sham and Ovx groups. These data matched our static data, which
      showed a significantly increased percentage of cortical bone area and decreased
      percentage of marrow area. These bone gains were not maintained in the 90-day Ris
      withdrawal group. For cancellous bone, the 60-day Ris-treated high bone mass was
      maintained in the withdrawal group and not maintained in Ris continmuously
      treated group. These results indicate the effects of constant and terminated use
      of Ris in cortical bone were different from those in trabecular bone in the
      proximal tibial metaphysis.

PMID- 10084398
TI  - Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in
      ovariectomized rats.
AB  - The effect of dietary vitamin K2 (menaquinone-7) on bone loss in ovariectomized
      (OVX) rats was investigated. OVX rats were freely given experimental diets
      containing menaquinone-4 (MK-4; 12mg/100g diet) or menaquinone-7 (MK-7;
      18.1mg/100g diet) for 24 days; MK-4 and MK-7 were equal in molar concentrations.
      This feeding caused a remarkable increase of MK-4 and MK-7 concentrations in the
      serum and femur of OVX rats. OVX-induced decrease in the femoral dry weight and
      femoral calcium content was prevented by the feeding of dietary MK-4 or NK-7. In
      separate experiments, OVX rats were freely given experimental diets containing
      the fermented soybean (natto; including 9.4 microg MK-7/100g diet) without or
      with added MK-7 (37.6 microg/100g diet) for 77 days. Feeding produced a
      significant elevation of MK-4 and MK-7 concentrations in the serum of OVX rats.
      In this case, a significant increase in the femoral MK-4 content was observed but
      MK-7 was not detected in the femoral tissues. OVX-induced decreases in the
      femoral dry weight and femoral calcium content were significantly prevented by
      the feeding of diets containing natto with MK-7 added (37.6 microg/100g diets).
      This study demonstrates that the intake of dietary MK-7 has a preventive effect
      on bone loss caused by OVX. This effect may be partly caused by MK-4, which is
      formed by degradation of MK-7.

PMID- 10084399
TI  - Intestinal absorption of calcium from calcium ascorbate in rats.
AB  - The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was
      investigated in normal rats. Each animal was perorally administered either 5mg
      (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca
      carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with
      45Ca using 45CaCl2. The amount of radioactivity in plasma was measured
      periodically up to 34h after dosing, and pharmacokinetic parameters were
      calculated from the radioactivity in plasma. The time taken to reach the maximum
      45Ca level (Tmax) did not differ among the three groups. The area under the
      plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was
      significantly higher than those for the CaCO3 and the CaCl2 groups. The
      radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than
      those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or
      significantly higher than those for the CaCl2 and CaCO3 groups for the high dose.
      Similar results were observed for whole-body 45Ca retention. Radioactivity in the
      femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the
      CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP
      1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0),
      triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer
      solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the
      rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII
      disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results
      indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or
      higher than, that from CaCl2 and significantly higher than that from CaCO3
      because of its high degree of solubility in the intestine. Therefore, Ca-AsA
      would be useful as a Ca supplement with relatively high absorption from
      intestine.

PMID- 10084400
TI  - The visualization and evaluation of bone architecture in the rat using three
      dimensional X-ray microcomputed tomography.
AB  - Microcomputed tomography allows the true three-dimensional structure of bone to
      be assessed by a nondestructive analysis. This article describes how this
      technique has for the first time been applied to rat bone to determine the
      effects of aging, ovariectomy, and antiresorptive drugs on bone structure and how
      these results compare with those determined by histological and histomorphometric
      techniques. During the procedure, a micro X-ray source is directed toward the
      bone sample. Modifications in the X-ray beam induced by bone crystals are
      determined for a range of acquisitions before three-dimensional reconstruction of
      bone architecture is performed. Morphometric parameters determined were
      trabecular bone volume/tissue volume, trabecular number, and trabecular
      thickness. The results show that ovariectomy has a dramatic effect on rat bone
      structure. Following treatment with the bone resorption inhibitor tiludronate,
      the morphometric parameters were significantly improved. The results obtained
      with three-dimensional microcomputed tomography were in agreement with
      observations made using classical techniques. Microcomputed tomography should
      prove useful for evaluating the antiresorptive effects of bisphosphonates on bone
      architecture and in allowing between-drug comparisons.

PMID- 10084401
TI  - Effect of nonweight bearing on tibial bone density measured by QCT in patients
      with hip surgery.
AB  - Tibial bone mineral density (BMD) was measured in 11 patients who had undergone
      hip joint surgery, including 10 women (22-61 years old; mean +/- SD = 42.6+/
      10.3) and 1 man (61 years old). Four patients received total hip replacement
      (THR), while the others underwent rotational acetabular osteotomy (RAO). In one
      case, the start of rehabilitation was delayed until 4 months after the surgery
      because of infection at the surgical site. Nine patients underwent hip surgery
      for osteoarthritis and 2 patients for avascular necrosis. These 2 patients had a
      history of medication with corticosteroid. BMD of the tibia on the surgically
      treated side was measured by a peripheral quantitative CT (pQCT) system, which
      provided three different BMD values of trabecular BMD in the distal portion,
      total BMD in the distal portion, and total BMD in the diaphysis. The measurements
      were obtained preoperatively, and at several time points postoperatively, at 2,
      4, 6, and 8 weeks and 3, 4, 5, 8, 12, 18, and 24 months after surgery. Brief
      periods of nonweightbearing lead to significant bone loss, and 1-1.5 years was
      required to recover to the baseline BMD. Accelerated bone loss was seen in
      patients in the perimenopausal state, with prolonged bed rest, and in patients
      receiving corticosteroid. Both trabecular and cortical components were influenced
      by nonweightbearing and restoration of weightbearing. The decrease in the
      cortical region occurs after the decrease in the trabecular and endosteal
      regions.

PMID- 10084402
TI  - A case of femoral neck fracture in a patient with severe testosterone deficiency.

PMID- 10084403
TI  - Mechanical responses and signal transduction pathways in stretched osteocytes.
AB  - Mechanotransduction in bone is complex in nature, being influenced by many
      modulators such as PTH, prostanoids, and extracellular Ca2+. It has been
      postulated that osteocytes, dendritic resident cells in bone, transduce signals
      of mechanical loading that result in anabolic responses such as the expression of
      c-fos, insulin-like growth factor-I (IGF-I), and osteocalcin. To date, however,
      neither the actual stimuli to which osteocytes respond nor the pathways of signal
      transduction are well understood. Cultured primary rat bone cells exhibit
      distinct responses to stretching depending on their developmental stages: young
      osteocytes that become progressively dendritic show striking responses to strain
      at physiological levels; these include an early response of cAMP secretion and
      the late responses such as the production of IGF-I and osteocalcin proteins. The
      upregulation of steady-state levels of their mRNA is biphasic, being preceded by
      two peaks of PGHS-2 (inducive prostaglandin G/H synthase; cox-2) gene expression.
      Compared to a typical transient immediate early expression of c-fos, PGHS-2 shows
      another distinct peak about 8 h after the initiation of stretching. Second peaks
      in IGF-I and osteocalcin expression are entirely dependent on the first wave of
      PGHS-2 expression judging from the inhibition by NS398. PGHS-2 is perhaps
      critically involved in the prolonged anabolic responses of bone "memory effect"
      to the osteogenic mechanical stimulation. In these cells, the extracellular Ca2+
      is essential to their response to stretching. Furthermore, the blockers of
      stretch-activated channels, gadolinium (Gd3+), and of epithelial-like Na
      channels, benzamil, in combination abolish the effects of stretching such as
      elevated osteocalcin expression. Although voltage-operated or calcium-activated
      calcium channels or Na+-driven mechanisms, such as a Na-Ca exchanger, for
      example, are functioning, particulars of secondary Ca entry pathways are not
      certain at this point. It is conceivable, however, that the calcium influxes,
      both primary and secondary, trigger the anabolic reaction of bone to stretching
      via Ser/Thr kinase signaling pathways in osteocytic cells.

PMID- 10084404
TI  - Establishment and characterization of an osteocyte-like cell line, MLO-Y4.
AB  - Much attention has focused on osteoblast and osteoclast biology, but little
      research has been performed on the cell that composes 90% of all bone cells--the
      osteocyte. Osteocyte function has been difficult to study because these cells are
      embedded in mineralized tissue and are difficult to obtain in reasonable numbers
      and purity. Establishment of an osteocyte cell line makes it possible to study
      osteocyte function more readily and easily by the application of protein
      chemistry and molecular biology. We have established a cell line that appears to
      have the properties of primary osteocytes.

PMID- 10084405
TI  - Identification of novel signaling pathways during functional adaptation of the
      skeleton to mechanical loading: the role of glutamate as a paracrine signaling
      agent in the skeleton.
AB  - The effect of exercise on the skeleton is to initiate an adaptive response so
      that high levels of activity induce increased bone formation, while disuse
      results in bone loss. This response tunes bone mass to an appropriate level with
      sufficient strength but not excessive mass, which would be energetically costly
      to build, maintain, or use. Interest in effects of exercise on bone stems from
      the prevalence of diseases that feature pathological, i.e., functionally
      inappropriate bone loss, such as osteoporosis. If exercise regimens can be
      specified that maximize bone mass in early life, then even after the catastrophic
      loss at menopause, the bone mass of women may remain above the threshold for
      fracture. In addition, fuller understanding of the cascade of cellular events
      that follow loading of bone cells provides target processes for pharmacological
      mimicry of the effects of exercise in vivo. Our studies therefore address these
      two areas, first to identify components of loading regimens that are osteogenic
      and second to identify novel genes which are regulated by loading. These studies
      have led directly to our work identifying expression of neuronal-type glutamate
      receptors in bone and the intriguing possibility that intercellular communication
      in bone may share numerous similarities with synapses in the central nervous
      system.

PMID- 10084406
TI  - Comparing the delivery of albuterol metered-dose inhaler via an adapter and
      spacer device in an in vitro infant ventilator lung model.
AB  - OBJECTIVE: To compare the delivery of an albuterol metered-dose inhaler (MDI)
      (Ventolin) via an Aerochamber (Monaghan) with an inline adapter (Medicomp
      Straight Swivel) in an in vitro infant lung model. METHODS: An in vitro infant
      lung model was modified to compare the delivery of albuterol MDI 10 inhalations
      via an Aerochamber with an inline adapter. The adapter and Aerochamber were
      placed at the endotracheal tube. A 1000 mL intravenous bag filled with 500 mL
      deionized water was attached to a 3.5 mm endotracheal tube (10 cm length). An
      Infant Bear Cub ventilator was used at the following settings: positive
      inspiratory pressure 20 cm H2O, intermittent mandatory ventilation 40
      breaths/min, positive end expiratory pressure 4 cm H2O, and inspiratory time 0.5
      second. Each device was run at least 10 times and assayed in duplicate by HPLC.
      An unpaired Student's t-test was used to analyze the statistical significance of
      the data. RESULTS: There was significantly greater delivery of albuterol with the
      Aerochamber (19.49 +/- 7.23 microg; 2.17% +/- 0.8%) as compared with an inline
      adapter (1.0625 +/- 1.36 microg; 0.12% +/- 0.15%) (p = 0.001). CONCLUSIONS: The
      Aerochamber provides a greater delivery of albuterol metered-dose inhalations to
      the lung than the inline adapter in an in vitro infant lung model.

PMID- 10084407
TI  - Evaluating the delivery of nebulized and metered-dose inhalers in an in vitro
      infant ventilator lung model.
AB  - OBJECTIVE: To evaluate drug delivery to the lungs of nebulized and metered-dose
      inhalers (MDIs) in an in vitro infant lung model. METHODS: An in vitro lung model
      was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL
      deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An
      inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL
      albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5
      L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the
      delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone
      MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was
      used at the following ventilator settings: positive inspiratory pressure 30 cm
      H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory
      pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10
      times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to
      analyze the statistical significance of the data. RESULTS: There was a
      significantly greater percentage of drug delivery with MDI albuterol (1.96 +/-
      0.50) as compared with nebulized albuterol (1.26 +/- 0.37) (p = 0.002) or
      beclomethasone diproprionate (0.51 +/- 0.24) (p = 0.001). CONCLUSIONS: Albuterol
      MDI provides a more efficient delivery of drug to the lung as compared with
      nebulized albuterol and MDI beclomethasone diproprionate.

PMID- 10084408
TI  - Medication use in residential care facilities for the elderly.
AB  - OBJECTIVE: To describe medication use by residents of residential care facilities
      for the elderly (RCFEs). DESIGN: A cross-sectional survey of medication use.
      SETTING: Licensed, private RCFEs recruited from a roster of all licensed RCFEs in
      the Los Angeles area. SUBJECTS: Residents who were > or =60 years of age and
      whose medications were centrally stored in the facility. MEASURES: Age, gender,
      race, health insurance coverage, dietary restrictions, ambulation status, medical
      diagnoses, and medication profile. RESULTS: A total of 818 residents were
      surveyed. Residents were primarily white women who were >80 years. The average
      number of medications per resident was five; 94% of the sample took at least one
      medication. Cardiovascular drugs, central nervous system drugs, analgesics,
      diuretics, and potassium supplements were most commonly used. Use of multiple
      drugs within a therapeutic class was also common, with means ranging from 1.46 to
      1.81 per resident for the most commonly prescribed classes. Diagnoses supporting
      the use of many medications were not documented in the residents' health records.
      CONCLUSIONS: This RCFE sample was medically frail and took many medications. The
      frequent use of cardiovascular medication reflected the prevalence of cardiac
      disease in the elderly. The frequency of psychotropic drug use without a
      corresponding indication suggested prescribing for symptoms rather than
      documented medical conditions. Lack of recorded diagnoses limited the ability to
      evaluate drug therapy. Improved record keeping; periodic medication review; and
      resident, staff, and prescriber education are necessary to ensure appropriate
      medication use in this setting.

PMID- 10084409
TI  - Cost-minimization analysis of piperacillin/tazobactam versus imipenem/cilastatin
      for the treatment of serious infections: a Canadian hospital perspective.
AB  - BACKGROUND: In 1998 we reported the first Canadian double-blind, randomized,
      clinical trial involving a comparison of piperacillin/tazobactam (P/T) with
      imipenem/cilastatin (I/C). The present study was conducted to determine the
      feasibility of replacing I/C at our institution. OBJECTIVE: To describe the
      outcome of a pharmacoeconomic analysis of the clinical trial from the perspective
      of a tertiary acute-care institution. METHODS: A total of 150 consenting adults
      originally prescribed I/C were randomly assigned to receive either P/T 4.5 g i.v.
      (n = 75) or I/C 500 mg i.v. (n = 75) every six hours. Actual direct medical
      resources used in relation to the treatment of bacterial infections were
      prospectively assessed during a clinical trial; these included cost of study and
      ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory
      assessments), and labor, as well as treatment of adverse drug reactions,
      antibiotic failures, and superinfections. RESULTS: While costs for successful
      treatment courses were similar across treatment arms, hospitalization costs for
      treatment course failures were higher for P/T recipients. Direct medical costs
      for treatment courses associated with a superinfection were also higher in the
      P/T arm. Overall costs for treatment failures with either study drug were at
      least twofold those observed for successful treatment courses. Mean total
      management cost per patient in the P/T group was $15,211 ($ CDN throughout) (95%
      CI $11,429 to $18,993), compared with $14,232 (95% CI $11,421 to $17,043) in the
      I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity
      analyses revealed that the superiority of I/C over P/T for successful treatment
      of serious infections was sensitive to changes in the cost of hospitalization and
      drug efficacy for either drug. CONCLUSIONS: Based on the results of the clinical
      trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes
      in hospitalized patients with serious infections. Under base-case conditions, our
      pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T
      at the dosage regimens studied. However, this finding was sensitive to plausible
      changes in both clinical and economic parameters.

PMID- 10084410
TI  - Chronic creatine kinase elevation not associated with HMG-CoA reductase inhibitor
      treatment.
AB  - OBJECTIVE: To report a case of chronically elevated creatine kinase (CK)
      concentration that is possibly associated with renal insufficiency and prostatic
      carcinoma. The goal is to raise awareness among clinicians who monitor CK
      concentrations in patients receiving hydroxymethylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitors. CASE SUMMARY: Because of an elevated CK concentration, a 64
      year-old African-American man with a history of chronic heart disease and renal
      insufficiency was assessed for possible myositis relating to his treatment with
      HMG-CoA reductase inhibitors. However, an association between the elevated enzyme
      concentration and drug treatment could not be clearly established. The patient
      was subsequently diagnosed with prostatic cancer and underwent a radical
      retropubic prostatectomy. The CK enzyme concentration declined following the
      surgery despite continuation of the drug therapy. DISCUSSION: CK is relatively
      nonspecific because of its wide distribution in human tissues. Although several
      findings of elevated CK concentrations, particularly the CK-BB isoenzyme, in
      patients with carcinoma or chronic renal insufficiency have been documented,
      these may not be common knowledge among clinicians. This case report provides an
      example of an unusually high CK enzyme concentration that may be linked to
      prostatic carcinoma and renal insufficiency. CONCLUSIONS: It is important to be
      aware of different causes for CK enzyme concentration elevation, especially when
      it is used as a monitoring parameter during HMG-CoA reductase inhibitor
      treatment. In a case of persistent elevated CK enzyme concentration without
      evidence of myositis, renal insufficiency may be a contributing factor and
      malignancy must be ruled out.

PMID- 10084411
TI  - Iritis associated with intravenous cidofovir.
AB  - OBJECTIVE: To report two patients with AIDS and cytomegalovirus retinitis who
      developed iritis after receiving intravenous cidofovir. Both experienced
      recurrent symptoms upon rechallenge. CASE SUMMARIES: Two HIV-positive patients
      with cytomegalovirus retinitis infections previously controlled with intravenous
      ganciclovir or foscarnet were treated with intravenous cidofovir. Symptoms of
      iritis developed after the second or third dose of cidofovir. One patient
      experienced symptoms unilaterally, while the other patient had bilateral
      symptoms. In both patients, the iritis resolved with topical ophthalmic therapy,
      but recurred following subsequent infusions of cidofovir. Therapy with cidofovir
      was discontinued, and no further recurrences of iritis were noted. One patient
      had post-inflammatory fixed dilated pupils. CONCLUSIONS: Iritis can uncommonly
      occur in patients receiving intravenous cidofovir and oral probenecid. With
      prompt drug discontinuation and administration of topical corticosteroids and/or
      mydriatic agents, symptoms are usually reversible.

PMID- 10084412
TI  - Hydrochlorothiazide-induced pulmonary edema and associated immunologic changes.
AB  - OBJECTIVE: To describe a patient with noncardiogenic acute pulmonary edema
      induced by hydrochlorothiazide and to investigate the possible involvement of an
      immunologic mechanism in this adverse reaction. CASE SUMMARY: A 66-year-old
      Hispanic woman developed acute pulmonary edema 30 minutes after the ingestion of
      one tablet of triamterene 75 mg/hydrochlorothiazide 50 mg. The reaction was
      associated with hemoconcentration; a decreased white blood cell count with a
      shift to a predominance of polymorphonuclear cells; decreased serum
      immunoglobulin (Ig) G, IgG1, and IgG4; and increased serum IgM and complement 3
      concentrations. DISCUSSION: Although there have been 35 reports of cases of
      hydrochlorothiazide-induced pulmonary edema, the etiology of this adverse
      reaction remains unknown. The observations presented in this case report, along
      with commonalities with previously reported cases, suggest that granulocytic
      infiltration into the lungs and IgG deposition in alveolar membranes may play a
      role in hydrochlorothiazide-induced pulmonary edema. CONCLUSIONS: Noncardiogenic
      pulmonary edema may be an immunologically mediated rare idiosyncratic reaction to
      hydrochlorothiazide.

PMID- 10084413
TI  - Miconazole oral gel enhances acenocoumarol anticoagulant activity: a report of
      three cases.
AB  - OBJECTIVE: To describe three cases of interaction between miconazole oral gel and
      acenocoumarol, manifested as an increase in the international normalized ratio
      (INR). CASE SUMMARIES: Three patients (62-year-old woman, 89-year-old woman, 43
      year-old man) following oral antithrombotic treatment with acenocoumarol for
      different pathologies were diagnosed with oral candidiasis and started miconazole
      oral gel. In all cases, the previous INR values were repeatedly within the
      therapeutic range. The following routine monitoring of the antithrombotic therapy
      showed a marked increase in anticoagulant activity in all cases, which returned
      to the therapeutic range after miconazole was withdrawn. None of the patients
      needed substantial changes in their habitual dosages of acenocoumarol in
      subsequent measurements of the INR to stay within the therapeutic range.
      DISCUSSION: We report three cases in which a possible interaction between
      miconazole oral gel and acenocoumarol is suggested by the chronological
      relationship between the introduction of miconazole and an increase in the INR.
      Miconazole exerts its fungistatic action by inhibiting some isoenzymes of the
      fungal cytochrome P450 system. Oral mucosa inflammation (as in oral candidiasis)
      may enhance its transmucosal absorption. In this setting, cytochrome P450
      isoenzymes belonging to the host may be inhibited too. This mechanism provides an
      explanation for different interactions observed with miconazole oral gel.
      CONCLUSIONS: Miconazole oral gel enhances acenocoumarol anticoagulant activity.
      Although we did not observe major bleeding complications, we suggest the use of
      other families of antifungal drugs, such as nystatin, to treat oral candidiasis
      in patients taking acenocoumarol.

PMID- 10084414
TI  - Pharmacologic management of Alzheimer disease, Part I: Hormonal and emerging
      investigational drug therapies.
AB  - OBJECTIVE: To provide information about current genetic research in Alzheimer
      disease (AD) and potential pharmacologic interventions. Investigational
      pharmacologic management of AD, including serenics, hormonal therapy,
      neurotransmitter augmentation, neurobiologic agents, nootropics, and ampakines
      are also reviewed. DATA SOURCES: Studies, review articles, and editorials
      identified from MEDLINE searches (from January 1993 to December 1996), and
      bibliographies of identified articles. STUDY SELECTION: Studies, review articles,
      and editorials addressing current areas of AD pharmacotherapy research, including
      hormonal therapy and select investigational agents. DATA EXTRACTION: Pertinent
      information was selected and the data were synthesized into a review format. DATA
      SYNTHESIS: AD is a devastating disease characterized by progressive memory loss,
      cognitive decline, and behavioral disturbances. The behavioral problems
      associated with AD can present a difficult clinical challenge. Many patients with
      AD are intolerant of traditional pharmacologic management, including
      antipsychotics, antidepressants, and anxiolytics. Hormonal agents, including
      estrogen, medroxyprogesterone, and cyproterone acetate, may be efficacious
      therapeutic alternatives in the management of sexual behavioral disturbances in
      men. Research regarding estrogen's role in AD prevention and effect on cognitive
      function and behavioral symptoms in women with AD are evaluated. Studies
      evaluating neurotransmitter augmentation and neurobiologic agents in AD are
      reviewed. CONCLUSIONS: Environmental, genetic, neurobiologic, hormonal, and
      neurotransmitter influences, and their respective roles in AD pathology, are
      being investigated. Researchers concur that it is imperative to recognize the
      correlation of these factors in the etiology of AD to design effective prevention
      and treatment strategies. Additional studies are essential to elucidate the most
      efficacious treatments for AD and the attendant behavioral disturbances.

PMID- 10084415
TI  - Pharmacologic management of Alzheimer disease, Part II: Antioxidants,
      antihypertensives, and ergoloid derivatives.
AB  - OBJECTIVE: To provide information about research evaluating antioxidants in
      Alzheimer disease (AD) and to discuss the potential role of beta-blockers,
      angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and
      ergoloid derivatives in AD therapy. DATA SOURCES: Studies, review articles, and
      editorials identified from MEDLINE searches (from 1989 to 1997) and
      bibliographies of identified articles. STUDY SELECTION: Studies and review
      articles addressing antioxidant, antihypertensive, and ergoloid derivative
      pharmacotherapy research. DATA EXTRACTION: Pertinent information was selected and
      the data synthesized into a review format. DATA SYNTHESIS: AD is a progressive
      neuropsychiatric disorder of unknown etiology. Studies evaluating the possible
      association between a free radical mechanism in AD and the potential role of
      antioxidants are reviewed. Additionally, the role of beta-blockers, angiotensin
      converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid
      derivatives in AD management are discussed. CONCLUSIONS: Preliminary evidence
      suggests that antioxidants may have a protective effect against the development
      of AD. Additional prospective, double-blind, placebo-controlled studies are
      needed to determine the role of antioxidants in the prevention and management of
      AD. Understanding the role of antioxidants in AD may suggest alternative agents
      that have similar pharmacologic activity. Beta-blockers may be an option to
      control agitation in AD patients for whom anxiolytics or antipsychotics are
      ineffective or are contraindicated because of their adverse effect profiles.
      Other agents that may have a role in AD therapy include angiotensin-converting
      enzyme inhibitors, nimodipine, and ergoloid derivatives. Clonidine and guanfacine
      have thus far shown little promise in improving cognitive function in AD. Further
      prospective, double-blind, placebo-controlled trials will be necessary to
      elucidate the role of these agents in AD management.

PMID- 10084416
TI  - The use of combination antiretroviral therapy in HIV-infected patients.
AB  - OBJECTIVE: To review the published clinical trials of combination antiretroviral
      therapy, current guidelines about the use of combination antiretroviral therapy,
      information regarding the impact of adherence on treatment effect, and the
      effects of combination antiretroviral therapy on morbidity and mortality.
      METHODS: A MEDLINE search (January 1986-March 1998) was performed to identify all
      relevant articles. Selected articles and abstracts from this time period and
      references from these selections were included for review. DISCUSSION: Nucleoside
      analog monotherapy treatment of HIV infection is inferior to treatment with
      multiple antiretroviral agents. With the availability of new classes of
      medications (protease inhibitors, nonnucleoside reverse transcriptase inhibitors
      [NNRTIs], and new nucleoside analogs, combination antiretroviral therapy is now
      more potent and more complex than ever. The use and effects of protease
      inhibitors in combination with nucleoside analogs has been well documented. The
      use of NNRTIs and combination protease inhibitor regimens are not as well
      documented but may prove to be at least as efficacious as single protease
      inhibitor-containing regimens. Increases in CD4+ cell counts of >100 cells/mm3
      and decreases in HIV RNA (viral load) of >2 log are common with these
      medications, with antiretroviral naive patients being more likely to have
      substantial responses to therapy than experienced patients. CONCLUSIONS:
      Combination antiretroviral therapy in HIV-infected patients is now the standard
      of care. Combination antiretroviral regimens have been shown to reduce, at least
      temporarily, the morbidity and mortality associated with HIV infection and AIDS.
      However, these regimens are quite complex for patients to adhere to successfully.
      While the true long-term effects of combination antiretroviral therapy are
      unknown, their current effects on the HIV epidemic are unquestionable.

PMID- 10084417
TI  - Atypical antipsychotics: Part II: Adverse effects, drug interactions, and costs.
AB  - OBJECTIVE: To compare the adverse effects, drug interactions, and costs of
      conventional and atypical agents, and to provide a summary of therapeutic
      guidelines. Part I compared the pharmacology, pharmacokinetics, and efficacy of
      atypical and conventional agents. DATA SOURCES: Information was retrieved from a
      MEDLINE English-language literature search from June 1986 to June 1998 and by
      review of references. Indexing terms included atypical antipsychotics,
      neuroleptics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and
      ziprasidone. STUDY SELECTION: Comparative studies were selected when possible;
      placebo-controlled studies were included when data were limited on newer atypical
      antipsychotics. DATA EXTRACTION: Emphasis was placed on properly designed
      clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect
      profile, and cost. DATA SYNTHESIS: Significant adverse effects are
      agranulocytosis with clozapine, dose-dependent extrapyramidal side effects (EPS)
      with risperidone, and neuroleptic malignant syndrome with clozapine and
      risperidone. Clinically relevant drug interactions may occur with clozapine
      lorazepam, clozapine-fluvoxamine, and sertindole-quinidine. Newer atypical agents
      have high acquisition costs but may reduce noncompliance and rehospitalization
      rates. CONCLUSIONS: Risperidone or olanzapine are recommended as first-line
      agents for schizophrenia due to accumulating controlled trials and clinical
      experience. Quetiapine should be considered with partial response or if EPS
      develop, and clozapine is an option with treatment-refractory patients. Atypical
      agents may contribute to a better quality of life, but conventional neuroleptics
      are the first choice for strictly cost considerations.

PMID- 10084418
TI  - Intravenous azithromycin.
AB  - OBJECTIVE: To review the pharmacology, microbiology, chemistry, pharmacokinetics,
      efficacy, safety, tolerability, dosage, administration, and economic issues of
      intravenous azithromycin. DATA SOURCES: A MEDLINE search from 1978 to May 1998 of
      the English-language literature and an extensive review of journals and meeting
      abstracts was conducted. Due to the lack of published literature concerning the
      efficacy, safety, and pharmacokinetics of the intravenous formulation of
      azithromycin, the manufacturer was also contacted and requested to supply
      information concerning intravenous azithromycin. DATA EXTRACTION: In vitro and
      preclinical studies were included, as well as data from Phase II and III clinical
      trials. Efficacy, pharmacokinetic, safety, and tolerability data were also
      supplemented with information from the manufacturer, due to the lack of published
      reports. DATA SYNTHESIS: Azithromycin, an azalide subclass of the macrolide
      antibiotics, is now available as an intravenous formulation. The intravenous form
      is approved for the treatment of community-acquired pneumonia caused by Chlamydia
      pneumoniae, Haemophilus influenzae. Legionella pneumophila, Moraxella
      catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus (methicillin
      sensitive), and Streptococcus pneumoniae, and for the treatment of pelvic
      inflammatory disease caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and
      Mycoplasma hominis in situations in which intravenous therapy is required. Its
      spectrum of activity, unique pharmacokinetics, and high and sustained tissue
      penetration allow for once-daily dosing with monotherapy in many cases. Clinical
      and bacteriologic response rates as well as the adverse event profile have been
      similar to or better than comparative agents. CONCLUSIONS: Azithromycin offers
      advantages over other agents due to its unique pharmacokinetics, high and
      sustained tissue penetration, and spectrum of activity. This allows for
      monotherapy and once-daily intravenous dosing for mild-to-moderate community
      acquired pneumonia or pelvic inflammatory disease in many instances. Future
      research should focus on total duration of antibiotic therapy and the need, or
      lack thereof, for extensive oral antibiotic follow-up.

PMID- 10084419
TI  - Cardiovascular effects of troglitazone.

PMID- 10084420
TI  - Treatment options for osteoporosis in chronic liver disease patients requiring
      liver transplantation.
AB  - As patient life expectancy rises after liver transplantation, osteoporosis
      becomes a significant contributor to morbidity and mortality. Patients who
      undergo liver transplant have an increased risk of bone fractures secondary to
      osteoporosis, relative to the general population. Risk factors (pre- and
      posttransplant) include treatment with steroids, alcohol abuse, smoking, poor
      nutritional status, immobility, reduced muscle mass, menopause, and hypogonadism.
      The role of cholestatic liver disease is well recognized, but as of yet, the
      underlying etiology is unknown. The role of immunosuppressants is also evident,
      but their exact contribution remains to be established. Currently, there are no
      established therapies for osteoporosis secondary to liver transplantation. Most
      of the therapeutic options have been extrapolated from usual treatment options
      for osteoporosis in the general population. It is reasonable to attempt to lower
      steroid dosages, especially with the availability of new and more potent
      immunosuppressants such as mycophenolate mofetil and tacrolimus. Potentially,
      high-risk patients could be identified early with BMD screening. Preventive
      measures could be instituted and patients could be monitored more closely for
      objective signs of osteoporosis, such as decline in BMD and early fractures.
      Calcium and vitamin D supplementation may be helpful in those with deficiencies
      or poor nutritional intake, as well as in women older than 25 years. The role of
      bisphosphonates and hormone replacement therapy remains equivocal as studies in
      transplant patients are currently lacking. Risk versus benefit must be weighed on
      an individual basis. Lifestyle measures should be instituted in all patients if
      possible.

PMID- 10084421
TI  - Factors associated with preventability, predictability, and severity of adverse
      drug reactions.
AB  - OBJECTIVE: To determine the rate of adverse drug reactions (ADRs) in hospitalized
      patients in an Iranian hospital and to assess factors associated with
      preventability, predictability, and severity of ADRs. DESIGN AND PARTICIPANTS: A
      prospective, randomized study was conducted on 370 patients in a hospital at the
      Tehran Medical Sciences University, from March to December 1996. Patients who
      experienced at least one ADR (n = 62) were entered into the database.
      Preventability, predictability, and severity of reactions were determined, based
      on the available algorithms developed by other investigators. SETTING: A 1200-bed
      tertiary care university teaching hospital in Tehran, Iran. RESULTS:
      Approximately 16.8% (n = 62) of the 370 patients who were included in this study
      had at least one ADR. One hundred two ADRs were reported during this study.
      Approximately 58.8% of the ADRs (60 reactions) were identified as preventable
      reactions and 96.1% as predictable reactions. The severity of 9.8% of the ADRs
      was identified as mild, 86.3% as moderate, 1% as severe, and 2.9% as lethal. The
      length of hospitalization increased with the severity of the ADRs. Preventable
      ADRs were more severe than those that were nonpreventable. In addition, the
      incidence of preventable ADRs increased with the patients' age and caused longer
      hospitalization than did nonpreventable ones. The most predictable ADRs were
      hematologic. CONCLUSIONS: This study noted that the rate of ADRs in Iran is
      probably as high as the rate in other parts of the world. These results indicate
      a need for a strong national ADR program that detects and reports adverse drug
      events in Iran.

PMID- 10084422
TI  - Rho Chi lecture. Pharmaceutical sciences in the next millennium.
AB  - Even a cursory survey of this article suggests that the pharmaceutical sciences
      are being rapidly transformed under the influence of both the new technologies
      and sciences and the economic imperatives. Of particular importance are
      scientific and technological advances that may greatly accelerate the critical
      process of discovery. The possibility of a drug discovery process built around
      the principles of directed diversity, self-reproduction, evolution, and self
      targeting suggests a new paradigm of lead discovery, one based quite directly on
      the paradigms of molecular biology. Coupled with the principles of
      nanotechnology, we may contemplate miniature molecular machines containing
      directed drug factories, circulating the body and capable of self-targeting
      against defective cells and pathways -- the ultimate "drug delivery machine."
      However, science and technology are not the only factors that will transform the
      pharmaceutical sciences in the next century. The necessary reductions in the
      costs of drug discovery brought about by the rapidly increasing costs of the
      current drug discovery paradigms means that efforts to decrease the discovery
      phase and to make drug development part of drug discovery will become
      increasingly important. This is likely to involve increasing numbers of
      "alliances," as well as the creation of pharmaceutical research cells -- highly
      mobile and entrepreneurial groups within or outside of a pharmaceutical company
      that are formed to carry out specific discovery processes. Some of these will be
      in the biotechnology industry, but an increasing number will be in universities.
      The linear process from basic science to applied technology that has been the
      Western model since Vannevar Bush's Science: The Endless Frontier has probably
      never been particularly linear and, in any event, is likely to be rapidly
      supplanted by models where science, scientific development, and technology are
      more intimately linked. The pharmaceutical sciences have always been an example
      of use-directed basic research, but the relationships between the pharmaceutical
      industry, small and large, and the universities seems likely to become
      increasingly developed in the next century. This may serve as a significant
      catalyst for the continued transformation of universities into the "knowledge
      factories" of the 21st century. Regardless, we may expect to see major changes in
      the research organizational structure in the pharmaceutical sciences even as
      pharmaceutical companies enjoy record prosperity. And this is in anticipation of
      tough times to come.

PMID- 10084423
TI  - Pediatric drug formulations: challenges and potential solutions.
AB  - Lack of pediatric drug formulations for both currently marketed and new drugs
      continues to be a challenge. Marketing of commercial products, along with
      pediatric indications, would be the ultimate solution to the lack of pediatric
      drug formulations. However, until that occurs, funding of research on
      extemporaneous formulations proposed by scientists should be a high priority.
      Government, academia, industry, the USPC, and professional associations should
      collaborate in developing the best policies and an action plan. Infants and
      children should not be expected to wait for stable extemporaneous formulations of
      important drugs until an unrealistic goal of having all generic and new drugs
      available commercially in suitable formulations has been realized.

PMID- 10084424
TI  - Clofazimine crystals in the cytoplasm of pulmonary macrophages.

PMID- 10084425
TI  - Comment: syncopal episodes associated with cisapride.

PMID- 10084426
TI  - Interaction between phenytoin and ciprofloxacin.

PMID- 10084427
TI  - Possible interaction between cyclosporine and chloramphenicol.

PMID- 10084428
TI  - Cutaneous and subcutaneous necrosis following dexrazoxane-CHOP therapy.

PMID- 10084429
TI  - Academy presidential address. No organization is an island unto itself.

PMID- 10084430
TI  - Intravenous pamidronate attenuates bone density loss after acute spinal cord
      injury.
AB  - OBJECTIVE: To compare the effects of a 6-month treatment with intravenous
      pamidronate (30-mg infusion once per month) to conventional rehabilitation
      without pamidronate on bone density of the spine and leg bones and on the
      excretion rate of N-telopeptide, a urinary marker of bone catabolism, in acutely
      spinal cord injured patients. DESIGN: A nonrandomized control trial in which 24
      spinal cord injured subjects entered the study within 6 weeks of their injury.
      Fourteen subjects received pamidronate; 10 did not. OUTCOME MEASURES: Bone
      density measurements by dual x-ray absorptiometry were performed before the
      initial treatment (within 6 weeks of the injury) and at 3, 6, and 12 months
      postinjury and was the primary efficacy parameter. Urine for N-telopeptide levels
      was the secondary efficacy parameter. RESULTS: After acute spinal cord injury,
      patients treated with intravenous pamidronate had significantly less bone density
      loss compared with those who did not receive pamidronate (parametric ANOVA,
      p<.02). Also, ambulatory subjects had significantly less bone density loss over
      the study period (p<.05) than nonambulatory subjects. In general, a high
      excretion level of the urinary bone-breakdown product N-telopeptide was found
      before intravenous pamidronate treatment, followed by a dramatic reduction in
      excretion after pamidronate treatment. Ambulatory subjects excreted significantly
      less N-telopeptide than motor-complete subjects at all time points. CONCLUSION:
      Intravenous pamidronate treatment and ambulatory ability in the first 6 months
      after an acute spinal cord injury prevents bone density loss.

PMID- 10084431
TI  - Postacute predictors of functional and cognitive progress in traumatic brain
      injury: somatosensory evoked potentials.
AB  - OBJECTIVE: To investigate the prognostic value of electrophysiologic studies
      performed during the postacute phase after traumatic brain injury (TBI). DESIGN:
      A prospective comparative study in which 26 patients with TBI participated.
      Patients were grouped according to their admission short-latency somatosensory
      evoked potential (SEP) results. Nonparametric Kruskal-Wallis and Mann-Whitney U
      tests were applied to different SEP groups to determine the differences among
      them in specific functional and cognitive outcome measures. SETTING: An inpatient
      brain injury rehabilitation unit. PARTICIPANTS: Twenty-six patients with TBI who
      were admitted to the rehabilitation center at the postacute phase for a late
      inpatient rehabilitation program and 15 age-matched healthy subjects who served
      as a control group for the electrophysiologic comparison. MAIN OUTCOME MEASURES:
      Motricity Index, Barthel Index, Disability Rating Scale, Mini-Mental Status Exam,
      and Rancho Los Amigos Scale. RESULTS: Disability Rating Scale scores at discharge
      and rate of change of Barthel Index scores differed between median nerve SEP
      classification groups (p<.05 for both). Disability Rating Scale scores at
      admission (p<.05) and at discharge (p<.01), Barthel Index scores at discharge
      (p<.05), and rate of change of Barthel Index scores (p<.05) differed between
      tibial nerve SEP classification groups. There was a relation between Motricity
      Index side scores at discharge and the different body side SEP response groups
      (p<.0001). Cognitive results showed no relation to the SEP groups. CONCLUSIONS:
      Postacute SEP scores after a late admission to a rehabilitation center showed a
      relation to measures of functional and motor progress. Patients with better SEP
      responses were more likely to experience greater functional and motor
      improvement. Cognitive functions were not related to SEP results.

PMID- 10084432
TI  - Exercise effect with the wheelchair aerobic fitness trainer on conditioning and
      metabolic function in disabled persons: a pilot study.
AB  - OBJECTIVE: To determine the effect of exercise with the wheelchair aerobic
      fitness trainer (WAFT) on anthropometric indices, conditioning, and endocrine and
      metabolic parameters in persons with lower extremity disability. DESIGN: Exercise
      sessions with the WAFT lasted 20 to 30 minutes for two to three sessions.
      SETTING: Tertiary-care Veterans Administration medical center. PARTICIPANTS:
      Twelve subjects (3 with quadriplegia, 7 with paraplegia, 1 with cerebrovascular
      accident, 1 with bilateral above-knee amputation). MAIN OUTCOME MEASURES:
      Anthropometric indices (heart rate, blood pressure, weight, oxygen utilization,
      body mass index, upper arm and abdominal circumference, arm power) and endocrine
      and metabolic parameters (fasting serum glucose, lipids, and thyroid function)
      were determined before and after 10 weeks of exercise with the WAFT. RESULTS: All
      patients noted improved feelings of well-being after training. Mean resting heart
      rate, upper arm fat area, and fasting serum cholesterol level decreased
      significantly. Peak oxygen consumption, midarm circumference, and free thyroxine
      index increased significantly with training. CONCLUSIONS: WAFT improves quality
      of life, conditioning, and endocrine-metabolic parameters in disabled persons.

PMID- 10084433
TI  - Functional reach: does it really measure dynamic balance?
AB  - BACKGROUND: Functional reach (FR) is a new clinical measurement intended to
      assess dynamic balance. The purposes of this study were (1) to measure the mean
      FR distance in healthy elders compared with individuals with known balance
      impairments, (2) to analyze the extent to which FR measures dynamic balance, and
      (3) to describe movement strategies used during FR. METHODS: Thirteen healthy
      elders and 15 individuals with vestibular hypofunction (VH) were tested during FR
      and free gait. Whole body kinematic and kinetic data including the center of
      gravity (CG) and center of pressure (CP) using 11 body segments and two force
      plates, respectively, were collected. RESULTS: There was no difference in FR
      distance between healthy elders and individuals with VH. FR distance was not
      correlated to lateral stability measures, but was related to anterior-posterior
      postural control measures of FR (r = .69 to .84) in both groups. Although FR
      distance strongly correlated with maximum moment arm during FR in both groups,
      the correlations were not as strong when the subjects were then classified by
      movement strategy. The mean moment arm during FR was significantly less than that
      of free gait. CONCLUSIONS: These data suggest FR does not measure dynamic
      balance; healthy elders and balance-impaired individuals with vestibular
      dysfunction attained the same FR distance and did so without increasing the
      moment arm during or at the end of FR. Recording the strategy used during FR,
      however, may provide other valuable information necessary in addressing balance
      control. Clinical implications of assessing movement strategy are discussed.

PMID- 10084434
TI  - Testing a motor performance series and a kinematic motion analysis as measures of
      performance in high-functioning stroke patients: reliability, validity, and
      responsiveness to therapeutic intervention.
AB  - OBJECTIVE: To assess measurement properties of motor performance tests when used
      with high-functioning stroke patients. DESIGN: Test-retest reliability study with
      an interval of 2 days; responsiveness study with assessment before and after
      training; validity study assessing the tests' ability to discriminate between the
      high-functioning stroke patients and healthy subjects. SETTING: Referral center
      for neurorehabilitation. PARTICIPANTS: Twenty-nine high motor-functioning stroke
      patients and 20 healthy control subjects. INTERVENTION: Two special training
      sessions per day on 5 consecutive days, plus regular therapy. OUTCOME MEASURES:
      Scores on the motor performance series, a two-dimensional tracking test, and a
      kinematic task analysis. RESULTS: All tests (except the bimanual test) were able
      to document performance deficits with these patients and showed a moderately high
      to high test-retest reliability without systematic trend from test to retest
      (intraclass correlation coefficients for main variables, .61 to .89). The
      kinematic task especially demonstrated changes after training (standardized
      response means for timing variables, .53 to .66). A subset of variables indicated
      a modifying effect of limb side, age, and gender. CONCLUSION: All tests (except
      the bimanual test) can be used for both cross-sectional and follow-up group
      studies with high-functioning stroke patients. Measurement properties and the
      lack of comprehensive normative data limit their use with individual patients.

PMID- 10084435
TI  - Kinematic characteristics of standing disequilibrium: reliability and validity of
      a posturographic protocol.
AB  - OBJECTIVE: To investigate retest reliability and concurrent validity of the
      fundamental measurements made of a posturographic protocol that employs quiet
      standing to quantify the severity and the nature of patients' postural
      disturbances. STUDY DESIGN: Retrospective complete block design. SETTING:
      Geriatric rehabilitation department. PARTICIPANTS: Thirty-six participants (age
      range, 67 to 86 yrs) having normal, moderate, or severe levels of disequilibrium.
      METHODS: Quiet standing was evaluated on three occasions using a three
      dimensional motion analysis system and a force platform. Eight testing
      conditions, designed to vary task difficulty by controlling the contributions of
      vision, foot proprioception, and base-of-support width, were administered. MAIN
      OUTCOME MEASURES: Retest reliability of body sway, joint alignment, body
      position, and motor coordination indicators were evaluated by intraclass
      correlation coefficients (ICCs). Concurrent validity of protocol measures was
      evaluated by the prediction of disequilibrium from a stepwise linear discriminant
      analysis. RESULTS: ICCs indicated high level of retest reliability for all
      variables but those of motor coordination, which was not influenced by testing
      conditions. Discriminant analysis resulted in a four-factor discriminator that
      included measures of body sway, position, alignment, and motor coordination. The
      derived linear discriminate function correctly classified 96% of the patients'
      level of disequilibrium. CONCLUSIONS: The posturographic protocol has the
      potential to be a useful tool for evaluating severity and nature of postural
      instability and the effects of pharmacologic and rehabilitative treatment.
      Results also indicate that combining direct body measurements with force-plate
      data has the potential to expose the underlying impairments that cause
      disequilibrium, determine their pathogenesis, and evaluate compensatory
      strategies.

PMID- 10084436
TI  - Static exercise-induced increase in blood pressure in individuals with cervical
      spinal cord injury.
AB  - OBJECTIVE: To compare the pressor response to static exercise in subjects with
      cervical spinal cord injury (SCI) at the C6 to C8 level with that in able-bodied
      control subjects. In these SCI subjects, the descending supraspinal sympathetic
      neurons and afferent pathways from the contracting muscles to peripheral vessels
      via the medullary cardiovascular center are damaged. DESIGN: Mean arterial blood
      pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine,
      renin activity, vasopressin, aldosterone, and human atrial natriuretic peptide
      were measured during a 2-minute period of sustained contraction of elbow flexor
      group muscle in 7 SCI subjects and 7 age-matched able-bodied control subjects.
      RESULTS: Static exercise resulted in a significant increase in mean blood
      pressure (p<.05) in both SCI subjects (pre-exercise. 74.7+/-2.2 mm Hg; static
      exercise, 81.9+/-4.1 mm Hg) and control subjects (pre-exercise, 101.0+/-4.2 mm
      Hg; static exercise, 117.0+/-4.9 mm Hg). In SCI subjects, there was no change in
      heart rate during exercise, whereas in control subjects heart rate increased
      during exercise (p<.05) (pre-exercise, 8.7+/-3.8 beats/min: static exercise,
      76.0+/-3.1 beats/min). There were no significant changes in the hormone levels in
      the SCI subjects throughout the experiment. CONCLUSION: The significant increase
      in mean blood pressure observed in the present study indicates the presence of
      peripheral control from muscle receptors and evoked pressor response during
      static exercise in SCI subjects.

PMID- 10084437
TI  - Frequency of videofluoroscopic modified barium swallow studies and pneumonia in
      stroke rehabilitation patients: a comparative study.
AB  - OBJECTIVE: To study the association between the frequency of videofluoroscopic
      modified barium swallow (VMBS) studies and the incidence of pneumonia in stroke
      rehabilitation patients. DESIGN: Retrospective comparative study. SUBJECTS AND
      SETTING: Five hundred sixty-three consecutive stroke patients admitted to one
      hospital rehabilitation unit in London, Ontario, Canada were compared with 461
      consecutive stroke patients admitted to another hospital rehabilitation unit in
      the same city. INTERVENTIONS: The number of initial and total VMBS studies and
      the timing from stroke onset to initial VMBS studies. MAIN OUTCOME MEASURE:
      Incidence of pneumonia. RESULTS: At the first hospital, 146 patients (25.9%) had
      232 total VMBS studies performed, whereas at the second hospital 57 patients
      (12.4%) had 73 total studies (p<.001). For the first 15 days there was no
      significant difference in the number of initial VMBS studies performed (8.2% vs.
      9.2%). There was a marked difference in the number of initial VMBS studies
      performed after 15 days (17.2% vs. 2.0%, p<.0001). The difference between the
      hospitals in the number of VMBS studies in patients with brain stem strokes was
      not statistically significant, but for patients with hemispheric stroke, the
      difference was statistically significant. Pneumonia developed in 12 patients at
      the first hospital (2.1%) and 10 patients at the second hospital (2.2%), a
      difference that was not significant. CONCLUSIONS: The more frequent use of VMBS
      beyond 15 days after stroke was not associated with a change in the incidence of
      pneumonia among hemispheric stroke rehabilitation patients, assuming the two
      units were otherwise similar.

PMID- 10084438
TI  - Clinical evaluation of the bionic glove.
AB  - OBJECTIVE: Clinical evaluation of the Bionic Glove, a prototype of a new
      functional electrical stimulation device designed to improve the function of the
      paralyzed hand after spinal cord injury. PATIENTS: Twelve people with spinal cord
      injury at C5-C7 who had used the device 6 months or more. SETTING: Measurements
      were made at the Institute "Dr Miroslav Zotovic" in Belgrade as a part of a
      multicenter clinical trial. METHODS: Measures include Upper Extremity Function
      Test, Functional Independence Measure, and Quadriplegia Index of Function.
      RESULTS: The daily use of a Bionic Glove had two major effects: (1) increasing
      the power grasp; and (2) increasing the range of movements. Active force was
      significantly greater than passive tenodesis force, as shown in other studies.
      Most manual tasks improved significantly with the use of the assistive system, as
      judged by the time needed to complete a task or the subject's qualitative ratings
      of a task difficulty. Most subjects who retained some dexterity without the
      assistive system hesitated to use the assistive system to manipulate small
      objects. CONCLUSION: The Bionic Glove can significantly improve independence in
      people with C5-C7 spinal cord injury if their initial Functional Independence
      Measure and Quadriplegia Index of Function scores are 20% to 50% of the maximum
      values.

PMID- 10084439
TI  - Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects
      on chronic clinical pain and acute experimental pain.
AB  - OBJECTIVE: To investigate to what extent a single 60-minute session of
      transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical
      pain, acute experimental pain, and the flexion reflex evoked in chronic low back
      pain patients. STUDY DESIGN: Thirty young subjects with chronic low back pain
      were randomly allocated to two groups, receiving either TENS or placebo
      stimulation to the lumbosacral region for 60 minutes. The flexion reflex was
      elicited by an electrical stimulation applied to the subject's right sole and
      recorded electromyographically from the biceps femoris and the tibialis anterior
      muscles. MAIN OUTCOME MEASURES: Subjective sensation of low back pain and the
      electrically induced pain were measured by two separate visual analog scales,
      termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60
      minutes after TENS and placebo stimulations were analyzed using repeated measures
      ANOVA. RESULTS: The VAS(LBP) score was significantly reduced to 63.1% of the
      prestimulation value after TENS (p<.001), but the reduction was negligible after
      placebo stimulation (to 96.7%, p = .786). In contrast, no significant change was
      found in the VASFR score (p = .666) and the flexion reflex area (p = .062) during
      and after stimulation within each group and between the two groups (p = .133 for
      VASFR and p = .215 for flexion reflex area). CONCLUSIONS: The same TENS protocol
      had different degrees of antinociceptive influence on chronic and acute pain in
      chronic low back pain patients.

PMID- 10084440
TI  - Reduction of pain-related behaviors with either cold or heat treatment in an
      animal model of acute arthritis.
AB  - OBJECTIVE: To assess the effects of heat and cold on quantifiable pain behaviors
      in an animal model of arthritis that minimizes the motivational-affective
      component of pain. DESIGN: The effects of superficial heat (40 degrees C) and
      cold (4 degrees C) on pain behaviors in rats with knee joint inflammation were
      tested before and after induction of inflammation and after treatment with heat
      or cold. SUBJECTS: Joint inflammation was induced in male Sprague-Dawley rats by
      intra-articular injection of the knee joint with 3% kaolin and 3% carrageenan.
      MAIN OUTCOME MEASURES: Withdrawal latency to heat applied to the paw (PWL)
      assessed secondary hyperalgesia; spontaneous pain behaviors assessed degree of
      weight bearing/ guarding; and joint circumference assessed joint swelling.
      RESULTS: Cold treatment of the inflamed knee joint significantly reversed the PWL
      immediately after treatment (p = .003) without affecting spontaneous pain
      behaviors orjoint circumference. In contrast, heat treatment produced a small but
      significant decrease in spontaneous pain behaviors (p = .03) without affecting
      PWL or joint circumference. CONCLUSION: Acute arthritic pain can be treated with
      either superficial heat for reducing guarding or with cold for reducing pain or
      hyperalgesia outside the injury site.

PMID- 10084441
TI  - Delayed onset muscle soreness: lack of effect of therapeutic ultrasound in
      humans.
AB  - OBJECTIVE: To investigate the effects of two dosages of pulsed ultrasound therapy
      (1 MHz, spatial averaged peak intensity 0.8 W/cm2, mark space ratio of 1:4) on
      acute-stage delayed onset muscle soreness (DOMS). DESIGN: Double-blind, placebo
      controlled, randomized trial. SETTING: Laboratory of a university physiotherapy
      department. PARTICIPANTS: Forty-eight healthy volunteers (24 men, 24 women) with
      no arm pathology or pain at the time of the study. INTERVENTIONS: Subjects were
      randomly allocated to one of four treatment groups: control, placebo (sham
      insonation), low-dosage pulsed ultrasound (mean dosage 172.8 J), or high-dosage
      pulsed ultrasound (mean dosage 345.6 J). DOMS was induced in the nondominant
      elbow flexors in a standardized fashion through repeated eccentric exercise until
      exhaustion. MAIN OUTCOME MEASURES: Elbow extension, flexion, and resting angles
      (universal goniometer), pain (visual analogue scale), mechanical pain
      threshold/tenderness (pressure algometer), and a McGill pain questionnaire.
      Measurements were taken before and after treatment each day except for the McGill
      pain questionnaire, which was completed at the end of the trial. RESULTS:
      Significant differences were seen between groups in relation to range of flexion
      (p = .0032), with the control group losing least range of flexion. There were no
      other significant differences between the groups. CONCLUSION: No convincing
      evidence was found to support the use of pulsed ultrasound therapy in the
      management of DOMS at the parameters discussed here.

PMID- 10084442
TI  - Wheelchair marathon racing causes striated muscle distress in individuals with
      spinal cord injury.
AB  - OBJECTIVE: To assess the effects of wheelchair marathon racing in individuals
      with spinal cord injury (SCI) on circulating muscle enzymes and myoglobin.
      SUBJECTS: Thirty-one men with SCI, including 25 wheelchair marathon athletes and
      6 sedentary men. DESIGN: Serum myoglobin (Mb), creatine kinase (CK) activity, and
      lactate dehydrogenase (LDH) were measured in participants of the 1995 Oita
      International Wheelchair Marathon Race (42.195 km). Blood samples were obtained
      24 hours before, immediately after, 24 hours after, and 7 days after the race.
      RESULTS: Marathon racing resulted in significant increases in serum Mb, total CK
      activity, and LDH (p<.01) after the race. The peak Mb and LDH levels occurred
      immediately after the race; total CK activity peaked 24 hours after the race.
      Evaluation of cardiac muscle enzymes showed no significant changes in two CK
      isoenzymes (CK-MM and CK-MB). CONCLUSIONS: Propulsion of the wheelchair in a
      marathon race induced muscle stress in athletes with SCI. Completion of the
      marathon race did not cause cardiac muscle damage, however. Elevated muscle
      enzyme levels likely resulted from muscle distress rather than from dehydration.

PMID- 10084443
TI  - Shoulder pain and dysfunction in hemiplegia: effects of functional electrical
      stimulation.
AB  - OBJECTIVE: To determine the influence of functional electrical stimulation (FES)
      on subluxation and shoulder pain in hemiplegic patients. DESIGN: Controlled study
      of 24 months' duration beginning in the first month after onset of stroke.
      SUBJECTS AND SETTING: One hundred twenty hemiplegic patients with both subluxed
      and painful shoulder were followed for rehabilitation before and after discharge
      between 1989 and 1993. All subjects received conventional rehabilitation based on
      the Bobath concept. In addition, patients were alternately assigned to a control
      group or to receive additional FES for 5 weeks on muscles surrounding their
      subluxed and painful shoulder. MAIN MEASURES: Clinical examinations, including
      range of motion, pain assessment, and x-rays, were performed at the start of the
      study, between the second and fourth weeks after onset of stroke, and
      subsequently at 6, 12, and 24 months. RESULTS: The FES group showed significantly
      more improvement than the control group in both pain relief (80.7% vs. 55.1%,
      p<.01) and reduction of subluxation (78.9% vs. 58.6%, p<.05). Furthermore,
      recovery of arm motion appeared to be significantly improved in the FES group
      (77.1% vs. 60.3% in the control group, p<.01). CONCLUSION: The FES program was
      significantly effective in reducing the severity of subluxation and pain and
      possibly may have facilitated recovery of the shoulder function in hemiplegic
      patients.

PMID- 10084444
TI  - Rural health professionals' satisfaction with a rehabilitation mobile outreach
      program.
AB  - OBJECTIVE: To assess the extent to which rural physicians and allied health
      professionals are satisfied with consultation services provided by an
      interdisciplinary rehabilitation outreach team. DESIGN: Descriptive survey.
      SETTING: A rehabilitation outreach team that travels to 14 rural communities in
      eastern and northern Ontario, Canada. SUBJECTS: Thirty-six rural physicians
      (response rate, 53.7%) and 62 allied health professionals (response rate, 92.5%)
      involved in the care of patients referred to the program. MAIN OUTCOME MEASURE:
      Consumer satisfaction questionnaire. RESULTS: Most respondents (94.7%) indicated
      that they were satisfied with the interdisciplinary consultation, with comparable
      rates of satisfaction reported by physicians and allied health professionals. The
      highest satisfaction ratings were given to items addressing the clarity of
      recommendations provided by team members and the quality of the team's
      interaction with patients. The lowest ratings were associated with the waiting
      time between visits. Of all the individual disciplines on the team, physiatry was
      rated as most important for rural consultations. However, in open-ended comments,
      respondents indicated that the interdisciplinary aspect of the service was its
      most valued characteristic, whereas infrequent visits were the greatest drawback.
      CONCLUSION: The interdisciplinary outreach approach to rehabilitation
      consultation receives high satisfaction ratings from rural health professionals
      who refer patients to the outreach team, which supports this model as a way to
      enhance rehabilitation services in rural communities.

PMID- 10084445
TI  - Antidepressant exacerbation of spasticity.
AB  - Patients with spinal cord injury (SCI) may develop depression. This may be
      related to adjustment to living with an SCI in addition to dealing with
      complications of the injury, such as spasticity. Pharmacologic treatment of
      depression can be difficult because of neurochemical and receptor changes that
      are associated with SCI. Newer antidepressant agents are purported to have
      selective activity by alteration of serotonergic neurotransmission. A case report
      is presented that illustrates exacerbation of spasticity by this family of
      antidepressant medications. Mechanisms possibly explaining this exacerbation of
      spasticity are the effects of serotonin on motor neuron and reflex activity,
      denervation supersensitivity, and the serotonin syndrome. Understanding the
      relationship between serotonergic systems and spasticity can be important in
      treating depression in patients with spasticity.

PMID- 10084446
TI  - Resistance to activated protein C as an etiology for stroke in a young adult: a
      case report.
AB  - Resistance to activated protein C (R-APC) is an inherited, autosomal dominant,
      coagulation abnormality that is increasingly recognized as an important etiology
      for thromboembolic disease and stroke in young adults. This report describes the
      case of a 27-year-old woman taking oral contraceptives who experienced an acute
      thrombotic right hemispheric stroke. Three days after rehabilitation admission
      (33 days after stroke) she developed a left femoral deep venous thrombosis (DVT)
      despite appropriate prophylaxis. Further diagnostic workup for the stroke and DVT
      identified R-APC, possibly exacerbated by oral contraceptives, as the etiology.
      Hematology consultation recommended lifetime anticoagulation with warfarin. The
      patient's family history revealed that a 19-year-old cousin had died of a stroke
      several years earlier. Several months after discharge, an acute DVT occurred in
      the patient's 28-year-old brother, who tested positive for factor V Leiden, a
      genetic abnormality closely associated with R-APC. A thrombotic stroke occurred
      in her grandfather a few months later, but he was not tested. Her father
      demonstrated a "borderline" positive R-APC test and probably represents the
      genetic link. Indications for patient and family screening regarding R-APC and
      other forms of hereditary thrombophilia and implications for rehabilitation
      medicine physicians are discussed.

PMID- 10084447
TI  - Psychometric intelligence in patients with traumatic brain injury: utility of a
      new screening measure.
AB  - OBJECTIVE: To evaluate the validity of the General Ability Measure for Adults
      (GAMA) in a sample of patients with traumatic brain injury (TBI). DESIGN:
      Comparison with criterion standards of Wechsler Adult Intelligence Scale-Revised
      (WAIS-R) and measures of injury severity. SETTING: Regional rehabilitation
      center. PARTICIPANTS: One-year prospective series of consecutive rehabilitation
      referrals, including 42 adult patients with TBI. MAIN OUTCOME MEASURES: GAMA and
      WAIS-R IQ scores were obtained within 1 year after injury and compared with each
      other and with measures of injury severity. RESULTS: The GAMA demonstrated
      statistically significant covariance with the WAIS-R and was able to discriminate
      severe TBI from mild/moderate TBI. The correlation between the GAMA and length of
      coma fell just short of statistical significance. CONCLUSIONS: The GAMA is
      sufficiently sensitive to the presence or absence of severe TBI but may not be
      sufficiently sensitive to the exact degree of injury severity.

PMID- 10084448
TI  - Meralgia paresthetica secondary to limb length discrepancy: case report.
AB  - Meralgia paresthetica consists of pain and dysthesia in the lateral thigh caused
      by entrapment of the lateral femoral cutaneous nerve (L2-L3) underneath the
      inguinal ligament. Abdominal distension, tight clothing, and hip hyperextension
      are all described causes of this condition. To our knowledge this has never been
      attributed to a limb length discrepancy. We present a 51-year-old man with a long
      standing history of right sided meralgia paresthetica. History and physical and
      radiological examination were unrewarding except that his left leg was shorter
      than the right by 2 cm. Nerve conduction studies of the lateral femoral cutaneous
      nerve on the left had a normal latency and amplitude but were absent on the
      right. To prove the hpothesis that the limb length discrepancy was responsible
      for the condition, a single subject study was performed. The presence or absence
      of pain and dysesthesia in the right thigh was the observed behavior.
      Intervention consisted of wearing a 1.5-cm lift in the left or right shoe for 2
      weeks each with an intervening 2-week lift-free period. Pain was recorded on a
      numeric scale and numbness as being present or absent. There was continuing pain
      without and with the lift in the right shoe but no pain or numbness with the lift
      in left shoe. It was concluded that the limb length discrepancy was responsible
      for the meralgia paresthetica. Pertinent literature and possible pathomechanics
      are discussed.

PMID- 10084449
TI  - Evaluation of the cushion setting on performance of a Biodex II dynamometer.
AB  - OBJECTIVES: To compare the effects of the soft cushion setting with those of the
      hard cushion setting of a Biodex II isokinetic dynamometer on peak velocity and
      peak torque with six loads at 23 preset speeds. DESIGN: Mixed within- and between
      groups, repeated-measures design. SETTING: Research laboratory of a physical
      therapy education program. INTERVENTIONS: Each load was strapped onto the right
      knee attachment of the dynamometer and was dropped through a 100 degrees arc of
      motion five times at each preset speed using the soft and hard cushion settings.
      MAIN OUTCOME MEASURES: Peak velocity, peak torque, time to peak velocity, time to
      peak torque. RESULTS: Peak velocity was significantly influenced by the cushion
      setting, the weight dropped, and the preset speed. Maximal peak velocity achieved
      was 400 degrees/sec. Peak torque was influenced significantly by the cushion
      setting, the load, and the preset speed. Maximal peak torque measured was 34.99
      kg-m. CONCLUSION: The rotating shaft of Biodex II dynamometer moved at a slower
      speed through the entire arc of motion at the soft cushion setting and often
      failed to achieve a constant, preset speed. Peak torque measured using the soft
      cushion setting was more variable and therefore questionable.

PMID- 10084450
TI  - Traumatic brain injury.

PMID- 10084451
TI  - Practice parameter for electrodiagnostic studies in ulnar neuropathy at the
      elbow: summary statement. American Association of Electrodiagnostic Medicine,
      American Academy of Physical Medicine and Rehabilitation, American Academy of
      Neurology.

PMID- 10084452
TI  - Overview of resistance in the 1990s.
AB  - The tremendous therapeutic advantage afforded by antibiotics is being threatened
      by the emergence of increasingly resistant strains of microbes. Selective
      pressure favoring resistant strains arises from misuse and overuse of
      antimicrobials (notably extended-spectrum cephalosporins), increased numbers of
      immunocompromised hosts, lapses in infection control, increased use of invasive
      procedures and devices, and the widespread use of antibiotics in agriculture and
      animal husbandry. Outside the hospital, penicillin-resistant Streptococcus
      pneumoniae is of greatest concern; recent reports also indicate the appearance of
      outpatient methicillin-resistant Staphylococcus aureus (MRSA) infections. MRSA is
      a significant problem in the hospital, as are vancomycin-resistant Enterococcus,
      oxacillin-resistant S aureus, and multidrug-resistant Gram-negative bacilli.
      Owing to the high rate of antibiotic use and other risk factors, a person is more
      likely to acquire an antibiotic-resistant infection in the ICU than anywhere
      else, either inside or outside the hospital. Responsible antibiotic use and
      stringent infection-control policies are needed to discourage the development of
      resistant strains.

PMID- 10084453
TI  - Treatment of community-acquired pneumonia--IDSA guidelines. Infectious Diseases
      Society of America.
AB  - The Infectious Diseases Society of America (IDSA) has published guidelines for
      the treatment of community-acquired pneumonia (CAP). Although Streptococcus
      pneumoniae remains the most common etiologic agent, Chlamydia pneumoniae and
      Legionella pneumophila are also important causes. For all suspected CAP patients,
      particularly those requiring hospitalization, chest radiographs are strongly
      recommended to confirm the diagnosis. The IDSA guidelines, in contrast to those
      published by the American Thoracic Society, emphasize the use of sputum Gram's
      stain and culture in all patients, whenever possible, to establish etiology. This
      information can be used not only to guide therapy but also to track trends in the
      etiologic pathogens for CAP and their antibiotic susceptibility. In light of the
      better outcomes with the earliest possible interventions, the IDSA recommends
      initial empiric antimicrobial therapy until laboratory results can be obtained to
      guide more specific therapy. Macrolides, doxycycline, and fluoroquinolones are
      suggested for primary empiric therapy, since each has activity against common
      bacterial pathogens and atypical agents. Detailed antibiotic recommendations are
      made for various pathogens. For inpatients, attempts should be made to cover
      Legionella and other common pathogenic bacteria. Alternative antibiotics are
      recommended for patients with structural diseases of the lung, penicillin
      allergy, or suspected aspiration pneumonia. Switch to an appropriate oral
      antibiotic is recommended as soon as the patient's condition is stable and he or
      she can tolerate oral therapy, often within 72 h.

PMID- 10084454
TI  - Commentary on the 1993 American Thoracic Society guidelines for the treatment of
      community-acquired pneumonia.
AB  - Early treatment of community-acquired pneumonia (CAP) is associated with improved
      outcome. Since extensive diagnostic testing identifies an etiologic agent in only
      half of the cases and usually requires several hours or even days for results,
      CAP is most often initially treated empirically. In 1993, the American Thoracic
      Society (ATS) established guidelines to assist primary care physicians in
      antibiotic selection for the initial empiric treatment of CAP in immunocompetent
      adults. Since publication of the guidelines, the incidence of certain bacteria
      has been redefined, antimicrobial resistance patterns have changed, risk factors
      for stratifying need for hospitalization have been further defined, and newer
      antibiotics have been introduced. These changes necessitate a reevaluation of the
      1993 ATS guidelines. This article proposes a modification of the ATS guidelines.
      This modification continues to classify patients into groups, based on specific
      risk factors, to which a limited number of likely pathogens are identified and
      for which antibiotic treatment regimens are developed. The modification differs
      from the original ATS guidelines because of the changes in risk factors. Patient
      groups are still broadly divided into outpatient and inpatient care, but earlier
      risk factors of age and coexisting illness have been refined. Risk factors
      suggested herein as considerations to guide treatment include the presence of
      cardiopulmonary disease, history of smoking, severity of illness, risk of drug
      resistant Streptococcus pneumoniae and Pseudomonas aeruginosa, and need for ICU
      admission.

PMID- 10084455
TI  - Pharmacodynamic principles of antimicrobial therapy in the prevention of
      resistance.
AB  - Pharmacodynamic properties can be used to divide antibiotics into two major
      classes based on their mechanism of bactericidal action: (1) concentration
      dependent drugs, such as aminoglycosides and fluoroquinolones, and (2)
      concentration-independent drugs, including the beta-lactams. Antibiotics also
      differ in the postantibiotic effect (PAE) that they exert. In general,
      concentration-dependent drugs have a more prolonged PAE than concentration
      independent drugs, particularly against Gram-negative pathogens. Pharmacodynamic
      classifications have important implications for the planning of drug regimens.
      For concentration-dependent drugs, peak concentration to minimal inhibitory
      concentration (MIC) ratios of approximately 10 are associated with clinical
      success. Therefore, high drug levels should be the goal of therapy. This is best
      achieved by high doses taken once daily. This approach, however, is not feasible
      for the fluoroquinolones owing to dose-limiting CNS toxicity. Concentration
      independent agents are most effective when the duration of serum concentrations
      is higher than the pathogen's MIC (time >MIC) for a significant proportion of the
      dosing interval. Frequent dosing or continuous infusions can increase the time
      >MIC. Concentrations of antibiotics that are sublethal can permit the emergence
      of resistant pathogens. Optimization of antibiotic regimens on the basis of
      pharmacodynamic principles could thus significantly diminish the emergence of
      antibiotic resistance.

PMID- 10084456
TI  - New intervention strategies for reducing antibiotic resistance.
AB  - Rising antibiotic resistance rates among bacterial pathogens have resulted in
      increased morbidity and mortality from nosocomial infections. Widespread use of
      certain antibiotics, particularly third-generation cephalosporins, has been shown
      to foster development of generalized beta-lactam resistance in previously
      susceptible bacterial populations. Reduction in the use of these agents (as well
      as imipenem and vancomycin) and concomitant increases in the use of extended
      spectrum penicillins and combination therapy with aminoglycosides have been shown
      to restore bacterial susceptibility. Studies have shown that education-based
      methods, as opposed to coercive measures, are effective in changing the
      prescribing habits of physicians. Cooperative interaction among infectious
      disease physicians, clinical pharmacists, microbiology-laboratory personnel, and
      infection-control specialists is essential to provide useful suggestions
      regarding antibiotic choice and dosing to the prescribing physician in real time.
      Several hospitals have implemented antimicrobial resistance management programs
      based on these findings. The results of these programs validate the use of a
      multidisciplinary, education-based, antibiotic-resistance management approach.

PMID- 10084457
TI  - Nosocomial pneumonia in the ICU--year 2000 and beyond.
AB  - Diagnostic and treatment strategies in ICU patients with ventilator-associated
      pneumonia (VAP) remain controversial, largely because of the paucity of well
      controlled comparison trials using clinically important end points. Recent
      studies indicating that early appropriate antibiotic therapy significantly lowers
      mortality underscore the urgent need for well-designed comparative trials. When
      quantitatively cultured, bronchial specimens obtained by noninvasive techniques
      may provide clinically useful information and avoid the higher costs and risks of
      invasive bronchoscopic diagnostic techniques. Previous antibiotic use before
      onset of nosocomial pneumonia raises the likelihood of infection with highly
      virulent organisms, such as Pseudomonas aeruginosa and Acinetobacter sp. Thus,
      the empiric antibiotic regimen should be active against these Gram-negative
      pathogens as well as other common Gram-negative and Gram-positive causative
      organisms. Promising preventive modalities for nosocomial VAP include use of a
      semirecumbent position, endotracheal tubes that allow continuous aspiration of
      secretions, and heat and moisture exchangers. Rotating their standard empiric
      antibiotic regimens and restricting the use of third-generation cephalosporins as
      empiric therapy may help hospitals reduce the incidence of nosocomial pneumonia
      caused by resistant Gram-negative pathogens.

PMID- 10084458
TI  - Nosocomial infections in the ICU: the growing importance of antibiotic-resistant
      pathogens.
AB  - Patients hospitalized in ICUs are 5 to 10 times more likely to acquire nosocomial
      infections than other hospital patients. The frequency of infections at different
      anatomic sites and the risk of infection vary by the type of ICU, and the
      frequency of specific pathogens varies by infection site. Contributing to the
      seriousness of nosocomial infections, especially in ICUs, is the increasing
      incidence of infections caused by antibiotic-resistant pathogens. Prevention and
      control strategies have focused on methicillin-resistant Staphylococcus aureus,
      vancomycin-resistant Enterococcus, and extended-spectrum beta-lactamase-producing
      Gram-negative bacilli, among others. An effective infection control program
      includes a surveillance system, proper handwashing, appropriate patient
      isolation, prompt evaluation and intervention when an outbreak occurs, adherence
      to standard guidelines on disinfection and sterilization, and an occupational
      health program for health-care providers. Studies have shown that patients
      infected with resistant strains of bacteria are more likely than control patients
      to have received prior antimicrobials, and hospital areas that have the highest
      prevalence of resistance also have the highest rates of antibiotic use. For these
      reasons, programs to prevent or control the development of resistant organisms
      often focus on the overuse or inappropriate use of antibiotics, for example, by
      restriction of widely used broad-spectrum antibiotics (e.g., third-generation
      cephalosporins) and vancomycin. Other approaches are to rotate antibiotics used
      for empiric therapy and use combinations of drugs from different classes.

PMID- 10084459
TI  - Conundrums in sleep medicine.

PMID- 10084460
TI  - Blow dry your asthma.

PMID- 10084461
TI  - Cryptococcal lung disease in patients without HIV infection.

PMID- 10084462
TI  - Paradigm shift in empyema management.

PMID- 10084463
TI  - Assessing quality of care using in-hospital mortality: does it yield informed
      choices?

PMID- 10084464
TI  - Critical care outcomes in the United Kingdom: sobering wake-up call or stability
      of the lamppost?

PMID- 10084465
TI  - Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?
AB  - OBJECTIVE: To determine the efficacy of inhaled salbutamol (rapidly delivered,
      using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum
      potassium levels in patients with hyperkalemia. DESIGN: A randomized, double
      blind, placebo-controlled trial. PATIENTS: Seventeen chronic renal failure
      patients referred to the Nephrology Unit between October 1, 1997 and March 31,
      1998 for hemodialysis were randomized. INTERVENTION AND RESULTS: Group 1 received
      salbutamol followed by a placebo. Group 2 received a placebo followed by
      salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an
      MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and
      after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly
      measured. Insulin levels were examined in a subset of patients (n = 10) before,
      and 1 and 5 min following inhalation. Salbutamol's known side effects,
      palpitation, tachycardia tremor, and headache, were recorded. Potassium levels
      rose after 1 min following the completion of treatment and then decreased
      steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients
      (59%) during the treatment period and there was no change (0%) seen during the
      placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol,
      potassium levels declined as a function of time. Potassium levels in those
      patients taking the placebo did not change as a function of time (p < 0.001). The
      difference between the placebo and the salbutamol-treated periods reached
      significance after 5 min (p < 0.05). The serum glucose levels rose following
      inhalation of salbutamol, with a significant rise after 3 min. The heart rate
      rose significantly within the first 5 min following inhalation. Serum insulin
      levels remained unchanged 1 min after inhalation; however, after 5 min, a
      significant elevation was detected. CONCLUSION: Salbutamol inhalation of 1,200
      microg, using an MDI-S, has a relatively rapid onset of action that induces a
      consistent reduction in serum potassium levels, starting 3 to 5 min following
      delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium
      levels in the first minutes following inhalation. This effect, although minor
      (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol
      inhalation as the first treatment for excessive hyperkalemia.

PMID- 10084466
TI  - A bolus of inhaled budesonide rapidly reverses airway subsensitivity and beta2
      adrenoceptor down-regulation after regular inhaled formoterol.
AB  - BACKGROUND: Subsensitivity of airway beta2-adrenoceptors develops readily in
      asthmatics receiving regular long-acting beta2-agonists. This subsensitivity may
      be rapidly reversed by using systemic corticosteroids. The purpose of the present
      study was to investigate whether the same acute facilitatory effects occur when
      using a bolus dose of inhaled corticosteroid. METHODS: Ten subjects with stable
      mild-to-moderate asthma, with a mean age of 27 years, mean (+/- SD) FEV1 of 2.95
      L (0.94 L), 81% (15%) of predicted, all receiving inhaled corticosteroids,
      reactive to adenosine monophosphate (AMP) with a provocative concentration
      producing a 20% fall in FEV1 (PC20) < 200 mg/mL, were recruited into a randomized
      double-blind crossover study. The subjects received two separate 1-week treatment
      periods with formoterol dry powder, 24 microg bid, with an initial 1-week run-in
      and a 1-week washout period between the treatments. A single dose of placebo or
      budesonide turbuhaler, 1,600 microg, was taken in conjunction with the last dose
      of both treatment periods. AMP challenge was performed 2 h after the first and
      last dose of formoterol. Blood for lymphocyte beta2-adrenoceptor density (Bmax)
      was also measured before and after treatment with formoterol. RESULTS: There was
      no significant difference in the geometric mean PC20 after the first dose of
      formoterol comparing the two treatment periods: 362 mg/mL vs 391 mg/mL. The PC20
      after the last dose of formoterol was significantly higher (p < 0.05) in
      conjunction with budesonide than with placebo: 427 mg/mL vs 99 mg/mL, amounting
      to a 4.3-fold difference (95% confidence interval [CI], 1.1 to 16.6). For
      comparison within each treatment period, there was significant subsensitivity (p
      < 0.05) between the first and last dose of formoterol when the latter was given
      with placebo: 391 mg/mL vs 99 mg/mL, a 3.9-fold fall (95% CI, 1.0 to 15.2), but
      not when the latter was given with budesonide: 362 mg/mL vs 427 mg/mL, a 1.2-fold
      rise (95% CI, 0.5 to 2.8). Lymphocyte 02-adrenoceptor density (geometric mean
      Bmax: fmol/10(6) cells) also showed significant down-regulation (p < 0.05) by
      formoterol given with placebo: preformoterol 2.53 vs postformoterol 1.91, but not
      by formoterol given with budesonide: preformoterol 2.43 vs postformoterol 2.67.
      The Bmax was significantly higher (p < 0.05) with formoterol + budesonide as
      compared to formoterol + placebo, amounting to a 1.40-fold difference (95% CI,
      1.09 to 1.80). CONCLUSION: We have shown that a bolus dose of inhaled budesonide
      rapidly reverses subsensitivity to AMP bronchoprotection and associated beta2
      adrenoceptor down-regulation in asthmatics taking regular formoterol. Further
      studies are indicated to assess whether high-dose inhaled corticosteroids should
      be administered as soon as possible along with beta2-agonists during an acute
      episode of bronchoconstriction.

PMID- 10084467
TI  - Inhaled beclomethasone dipropionate reverts tolerance to the protective effect of
      salmeterol on allergen challenge.
AB  - STUDY OBJECTIVE: One week of regular treatment with salmeterol can induce
      tolerance to the protective effect of a beta2-agonist on early airway response to
      allergen (EAR). The objective was to assess whether inhaled corticosteroids
      revert tolerance to salmeterol. STUDY DESIGN: The study had a randomized, double
      blind, placebo-controlled design. PATIENTS AND METHODS: Twelve subjects with mild
      allergic asthma and positive result of specific bronchial provocation test (sBPT)
      to allergen underwent three sBPTs, separated by 1 week. sBPT was done in all
      subjects after a single dose (T1) and after 1 week of regular treatment with
      inhaled salmeterol (50 microg bid) (T2) in order to induce tolerance. Subjects
      were then randomized to receive either the same dose of salmeterol +
      beclomethasone dipropionate (BDP, 500 microg bid) (group 1, n = 6) or placebo +
      BDP (group 2, n = 6) for 1 week before sBPT (T3). RESULTS: After a single dose of
      salmeterol (T1), all subjects were protected against EAR, whereas after 1 week of
      regular treatment, the protective effect of salmeterol was totally or partially
      lost (T2). Maximum FEV1 percent fall (MaxdeltaFEV1%) after allergen inhalation
      was significantly higher at T2 than at T1. All subjects except one of group 1
      were protected against EAR after salmeterol + BDP (T3), and MaxdeltaFEV1% at T3
      (median, 12%; range, 4 to 6%) was significantly lower than T2 (median, 22%;
      range, 12 to 43%; p < 0.05 by Wilcoxon test). Subjects of group 2 did not show
      any significant protection against EAR after placebo + BDP treatment (T3)
      MaxdeltaFEV1% at T2 (median, 31%; range, 9 to 40%) and T3 (median, 31%; range, 3
      to 42%; not significant). CONCLUSIONS: In conclusion, the addition of inhaled BDP
      partially restored the bronchoprotective effect of salmeterol on allergen
      challenge that was lost after 1 week of regular treatment with salmeterol alone.
      This ability of BDP in reverting tolerance cannot be ascribed to a direct effect
      of corticosteroids per se on allergen challenge in this group of asthmatics.

PMID- 10084468
TI  - Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol
      compared with ipratropium alone and albuterol alone in COPD.
AB  - STUDY OBJECTIVE: To conduct a post hoc pharmacoeconomic evaluation of two double
      blind, randomized, prospective, parallel group studies comparing the long-term
      efficacy and safety of ipratropium combined with albuterol in a single
      inhalational canister against either bronchodilator agent alone in patients with
      COPD. PATIENTS: One thousand sixty-seven patients with COPD. METHODS: The dose of
      each bronchodilator was two puffs four times a day (42 microg of ipratropium
      bromide, 240 microg of albuterol sulfate). Pulmonary function testing was
      performed on days 1, 29, 57, and 85 of treatment. Outcomes, health-care resource
      consumption, and costs were compared for the three treatment groups over the 85
      day study period. A total of 1,067 patients were randomized in the two studies
      (albuterol alone, n = 347; ipratropium alone, n = 362; albuterol plus
      ipratropium, n = 358). RESULTS: Improvement in FEV1 and area under the FEV1
      response-time curve from time 0 to 4 h (FEV1AUC0-4) was significantly greater for
      the combination of albuterol plus ipratropium than either agent alone on all test
      days. Compared with albuterol, patients receiving ipratropium and ipratropium
      plus albuterol experienced significantly fewer COPD exacerbations and patient
      days of exacerbation. In addition, the increased frequency of exacerbations
      observed in the albuterol group was associated with a significant increase in the
      number of patient hospital days and antibiotic and corticosteroid use. As a
      result, the total cost of treatment over the study period was significantly less
      for ipratropium ($156 per patient) and ipratropium plus albuterol ($197 per
      patient) than for albuterol ($269 per patient). Increased cost-effectiveness,
      defined as total estimated treatment cost per mean change in FEV1AUC0-4, was
      observed in both treatment arms containing ipratropium. CONCLUSIONS: The
      inclusion of ipratropium in a pharmacologic treatment regimen is associated with
      a lower rate of exacerbations in COPD. The result is lower total treatment costs
      and improved cost-effectiveness.

PMID- 10084469
TI  - Long-term cardiovascular safety of salmeterol powder pharmacotherapy in
      adolescent and adult patients with chronic persistent asthma: a randomized
      clinical trial.
AB  - STUDY OBJECTIVES: This study investigates the long-term cardiovascular safety of
      salmeterol powder vs placebo in adolescent and adult patients with mild
      persistent asthma. DESIGN: Multicenter, randomized, double-blind, placebo
      controlled, parallel-group study. SETTING: Eighteen US clinical centers.
      PATIENTS: Three hundred fifty-two patients (> or = 12 years) with mild persistent
      asthma (duration > or = 6 months) requiring pharmacotherapy; with FEV1 of 70 to
      90% of predicted and without abnormal ECG/continuous ambulatory ECG (Holter).
      INTERVENTIONS: Randomized to twice-daily salmeterol powder (50 microg) or placebo
      via breath-actuated device for 52 weeks. Backup albuterol was available to
      control asthma symptoms. MEASUREMENTS AND RESULTS: Cardiovascular safety was
      regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h
      continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements,
      and review of adverse cardiovascular events. No deaths occurred during the study.
      No clinically significant between-group differences were observed in pulse rate,
      ECG QTc interval, median number of ventricular or supraventricular ectopic
      events, incidence of ventricular ectopic couplets and runs, or incidence of > 100
      ventricular or supraventricular ectopic events in 24 h. No clinically significant
      between-group differences were observed in arterial BP or incidence of adverse
      cardiovascular events. Salmeterol was well tolerated throughout the 52-week study
      period, with a cardiovascular safety profile similar to that of placebo.
      CONCLUSIONS: Long-term, twice-daily pharmacotherapy with salmeterol powder is
      safe and is not associated with unfavorable clinically significant changes in
      cardiac function or increases in cardiovascular adverse effects.

PMID- 10084470
TI  - A comparison of two challenge tests for identifying exercise-induced bronchospasm
      in figure skaters.
AB  - OBJECTIVES: Studies documenting the increased incidence of exercise-induced
      bronchospasm (EIB) in figure skaters have employed a method that incorporates on
      ice exercise with rink-side spirometry. The literature suggests that bronchial
      provocation challenge testing is better than exercise testing for identifying
      EIB. To test this hypothesis in figure skaters, a unique athletic population that
      trains and competes in cold air, we compared these two methods in the same
      individuals. PATIENTS/METHODS: Two challenge tests were performed on a group of
      competitive figure skaters (n = 29, 26 female subjects; mean+/-SD age = 12.3+/
      3.5 years): (1) rink-side (temperature = 14 degrees C, humidity = 60%) spirometry
      before and 1, 5, 10, and 15 min after 5 min of intense skating; and (2) eucapnic
      voluntary hyperventilation (EVH), breathing 5% CO2, 21% O2, balance N2 at a rate
      of 60% of maximum voluntary ventilation (not to exceed 70 L/min) for 5 min
      (temperature = 18 degrees C, humidity = 50%), with an identical pretest and
      posttest spirometry schedule. EIB was defined as at least one of the following: a
      > or =10% decline in Fev1; a > or = 20% decline in maximum midexpiratory flow
      rate; or a > or = 25% decline in peak expiratory flow rate. RESULTS: Sixteen of
      29 skaters (55%) developed EIB: 9 were positive by on-ice testing; 12 were
      positive by EVH testing; 5 were positive on both tests; on-ice testing missed 7
      skaters with EIB; EVH testing missed 4 with EIB. CONCLUSION: In the group of
      figure skaters studied, EVH challenge testing was better at identifying EIB than
      on-ice exercise testing. However, these data suggest that evaluation for EIB in
      athletes who train and compete in the cold should include exercise testing in
      cold air along with a challenge test such as EVH to increase the yield of
      positive responders.

PMID- 10084471
TI  - 24-h esophageal pH testing in asthmatics: respiratory symptom correlation with
      esophageal acid events.
AB  - BACKGROUND: Gastroesophageal reflux (GER) may be a trigger for asthma and may be
      clinically silent. Twenty-four-hour esophageal pH testing accurately diagnoses
      GER in asthmatics. There are no reports correlating respiratory symptoms with
      esophageal acid events. This study examines the prevalence and severity of GER in
      asthmatics with and without reflux symptoms and examines respiratory symptom
      correlation with esophageal acid. METHODS: All esophageal manometry and 24-h
      esophageal pH tests performed were reviewed in asthmatics who met entrance
      criteria from July 1, 1989, through November 1, 1994. GER was present if
      esophageal pH tests were abnormal. Results of esophageal tests were compared for
      asthmatics with reflux symptoms and GER and asthmatics without reflux symptoms
      and GER. Respiratory symptoms correlated with esophageal acid events if the
      esophageal pH was < 4 simultaneously with the respiratory event or within 5 min
      before its onset. RESULTS: Of 199 asthmatics who qualified for analysis, 164
      (82%) had reflux symptoms. The results of 24-h esophageal pH tests were abnormal
      in 118 of 164 asthmatics with reflux symptoms (72%), compared with 10 of 35
      asthmatics without reflux symptoms (29%). Among asthmatics with GER, 119 of 151
      respiratory symptoms (78.8%) were associated with esophageal acid. Seventy-six of
      84 reported coughs (90.5%) were associated with esophageal acid. Theophylline did
      not alter esophageal parameters. CONCLUSIONS: There is a strong correlation
      between esophageal acid events and respiratory symptoms in asthmatics with GER.
      Respiratory symptom correlation with esophageal acid events further supports that
      GER may be a trigger for asthma.

PMID- 10084472
TI  - The relationship between age and bronchial responsiveness: evidence from a
      population survey.
AB  - OBJECTIVES: Increased bronchial responsiveness is a feature of symptomatic
      asthma, and it predicts the onset of wheezing. We have investigated the
      relationship between bronchial responsiveness and age in a population sample with
      an age range of 45 to 86 years. DESIGN: Cross-sectional population survey.
      SETTING: Population of Central Manchester, UK. PARTICIPANTS: An age-stratified
      random sample of white adults aged > or = 45 years old and living in Central
      Manchester. They were recruited from their primary care physician (general
      practitioner) lists. Patients with confusion and patients who were housebound
      were excluded. MEASUREMENTS: Respondents to a mail questionnaire were invited to
      attend a methacholine bronchial challenge performed using the Newcastle dosimeter
      method. Respondents with ischemic heart disease or respondents taking oral
      steroids, beta-blockers, or anticholinergic medication were excluded. RESULTS: Of
      the 783 subjects contacted, 92.3% of the subjects responded, and 508 subjects
      returned enough information for us to deduce their suitability for the bronchial
      challenge. Of the 395 suitable subjects, 247 subjects participated (62.5% of
      those invited; 31.5% of the study population), and 208 participants completed the
      bronchial challenge. Participants were slightly younger than nonparticipants, but
      they were otherwise representative of the population. Increased bronchial
      responsiveness (provocative dose of methacholine causing a 20% fall in FEV1 < or
      = 200 microg) was present in 71 (34.1%) participants. Stepwise multiple
      regression analysis showed weak, independent, positive associations between
      bronchial responsiveness and age, and between bronchial responsiveness and the
      total immunoglobulin E level. There was an independent negative relationship
      between bronchial responsiveness and the airways caliber (expressed as
      standardized residuals; R2 = 0.29). CONCLUSIONS: We have found a high prevalence
      of increased bronchial responsiveness in this inner-city population of older
      adults. Bronchial responsiveness showed a weak independent positive association
      with age.

PMID- 10084473
TI  - Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.
AB  - OBJECTIVE: To evaluate the effect of salmeterol on asthma-specific quality of
      life in patients experiencing significant nocturnal symptoms. DESIGN: Randomized,
      double-blind, placebo-controlled, multicenter clinical trial. SETTING:
      Allergy/respiratory care clinics. PATIENTS: Nonsmokers > or = 12 years of age
      with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or
      = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening
      at least once during screening. INTERVENTIONS: Salmeterol, 42 microg, or placebo
      twice daily. Patients were allowed to continue theophylline, inhaled
      corticosteroids, and "as-needed" albuterol. MEASUREMENTS AND RESULTS: Outcome
      measures included Asthma Quality of Life Questionnaire (AQLQ) global and
      individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and
      supplemental albuterol use. Mean change from baseline for the global and domain
      AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared
      with placebo. At week 12, salmeterol significantly (p < 0.001 compared with
      placebo) increased mean change from baseline in FEV1, morning and evening PEF,
      percentage of symptom-free days, percentage of nights with no awakenings due to
      asthma, and the percentage of days and nights with no supplemental albuterol use.
      Significant improvements in PEF were observed after treatment with salmeterol
      regardless of concomitant treatment with theophylline (p < 0.05). CONCLUSIONS:
      These results provide evidence that validates the role of salmeterol in improving
      quality of life in patients with moderate persistent asthma who exhibited
      nocturnal asthma symptoms and supports the efficacy of salmeterol compared with
      that of placebo (ie, "as-needed" albuterol).

PMID- 10084474
TI  - Circadian variation of paroxysmal supraventricular tachycardia.
AB  - BACKGROUND: Various clinical manifestations of cardiovascular diseases have a
      pattern of circadian variation. In this study, we investigated whether the onset
      and duration of paroxysmal supraventricular tachycardia (PSVT) has a circadian
      variation. METHODS AND RESULTS: In our analysis, we included 105 patients with
      498 PSVT episodes. In this study, the onset of PSVT did not have a uniform
      distribution throughout the 24-h period. There were nearly equal peaks in the
      time periods from 8:00 to 9:00 AM, 12:00 to 1:00 PM, and 5:00 to 6:00 PM, with a
      trough at night. The duration of PSVT also did not show a uniform distribution
      throughout the 24-h period; it increased significantly during the daytime, with a
      peak between 1:00 and 2:00 PM, another peak between 6:00 and 7:00 PM, and a
      significant reduction at night. CONCLUSIONS: The onset and duration of PSVT
      showed a circadian variation. However, the time-oriented antiarrhythmic therapy
      for preventing PSVT needs further study.

PMID- 10084475
TI  - Partial pressure of oxygen is lower in the left upper pulmonary vein than in the
      right in adults with atrial septal defect: difference in P(O2) between the right
      and left pulmonary veins.
AB  - BACKGROUND: The right-to-left shunt at the atrial level is responsible for
      arterial hypoxemia in patients with atrial septal defect. OBJECTIVES: This study
      investigated the mechanism of arterial hypoxemia in patients with atrial septal
      defect by measuring the P(O2) in both the right and left upper pulmonary veins.
      SUBJECTS AND METHOD: We prospectively measured the P(O2) in the femoral artery
      and the right and left upper pulmonary veins during cardiac catheterization in 13
      adults (median age, 53 years) and 7 children (median age, 7 years) with secundum
      atrial septal defect. The adults and children were studied consecutively.
      Contrast echocardiography was performed to evaluate right-to-left shunt in all
      adults. RESULTS: Among the children, there were no patients showing arterial
      hypoxemia, and there was no difference in the P(O2) (+/-SD) between the right and
      left upper pulmonary veins (right, 100+/-3.8 mm Hg vs left, 100+/-7.8 mm Hg; p =
      0.92). However, arterial hypoxemia was present in 11 of the 13 adult patients,
      although contrast echocardiography showed more than a moderate degree of right-to
      left shunt in only four adults. The P(O2) was lower in the left upper pulmonary
      vein than it was in the right upper pulmonary vein in all adult patients (right,
      91.6+/-13.8 mm Hg vs left, 73.0+/-11.5 mm Hg; p < 0.0001). CONCLUSION: The P(O2)
      was lower in the left upper pulmonary vein than it was in the right upper
      pulmonary vein in adults with atrial septal defect. Care must be taken in
      measuring pulmonary blood flow if the P(O2) in the left upper pulmonary vein is
      low enough to influence oxygen content. The decreased P(O2) in the left upper
      pulmonary vein may contribute to arterial hypoxemia in addition to right-to-left
      shunt at the atrial level in adults with atrial septal defect.

PMID- 10084476
TI  - Effect of vitamin E on exhaled ethane in cigarette smokers.
AB  - STUDY OBJECTIVES: We hypothesized that micronutrient antioxidant intake may be
      one factor determining the development of significant COPD. Vitamin E was
      administered to smokers to determine if exhaled ethane was reduced and if ethane
      correlated with measures of lung function. STUDY DESIGN: Longitudinal placebo
      lead-in trial with posttreatment observation period. SETTING: Tucson Veterans
      Affairs Medical Center. PARTICIPANTS: Twenty-nine current stable smokers having
      no interest in smoking cessation. INTERVENTIONS: Spirometry, exhaled breath
      ethane measurements, and vitamin E and [-carotene plasma levels followed by 3
      weeks of placebo with repeat plasma vitamin levels and ethane measurements; next,
      3 weeks of vitamin E (dl-a-tocopherol), 400 IU po bid followed by plasma vitamin
      levels and breath ethane measurements; finally, 3 weeks without vitamins followed
      by breath ethane and plasma vitamin levels. RESULTS: Vitamin E treatment did not
      reduce ethane significantly. Exhaled ethane levels (mean + SD: pm/min/kg) were as
      follows: baseline, 7.39 + 5.39; after run-in period, 6.86 + 4.09; after vitamin
      E, 6.36+/-3.02; and final, 7.23+/-4.63. After vitamin E therapy, a significant
      negative correlation existed between exhaled ethane and FEV1/FVC. Pack-years of
      smoking at baseline and after vitamin E were significantly associated with ethane
      exhaled. Initial lung function was not significantly negatively associated with
      vitamin E-induced changes in exhaled ethane but a negative trend was found.
      CONCLUSIONS: Vitamin E alone, unlike the combination of vitamins C, E, and beta
      carotene, failed to reduced exhaled ethane in cigarette smokers. Exhaled ethane
      was correlated with pack-years of smoking. Smokers whose ethane values were found
      to fall the most tended to have better preserved lung function.

PMID- 10084477
TI  - Associations of smoking with hospital-based care and quality of life in patients
      with obstructive airway disease.
AB  - STUDY OBJECTIVES: To investigate the relationship between direct or environmental
      tobacco smoke (ETS) exposure and both hospital-based care (HBC) and quality of
      life (QOL) among subjects with asthma. STUDY DESIGN: We report baseline cross
      sectional data on 619 subjects with asthma, including direct or ETS exposure and
      QOL, and prospective longitudinal data on HBC using administrative databases for
      30 months following baseline evaluation. SETTING AND PATIENTS: Participants were
      health maintenance organization members with physician-diagnosed asthma involved
      in a longitudinal study of risk factors for hospital-based asthma care.
      MEASUREMENTS: Demographic characteristics and QOL were assessed with administered
      questionnaires, including the Marks Asthma Quality-of-Life (AQLQ) and SF-36
      questionnaires. HBC was defined as episodes per person-year of hospital-based
      asthma care, which included emergency department and urgency care visits, and
      hospitalizations for asthma. RESULTS: Current smokers reported significantly
      worse QOL than never-smokers in two of five domains of the AQLQ (p < 0.05).
      Subjects with ETS exposure also reported significantly worse QOL than those
      without ETS exposure in two domains (p < 0.05). On the SF-36, current smokers
      reported significantly worse QOL than never-smokers in five of nine domains (p <
      0.05). Subjects with ETS exposure reported significantly worse QOL than those
      without ETS exposure in three domains (p < 0.05). Current smokers used
      significantly more hospital-based asthma care than never-smokers (adjusted
      relative risk [RR], 1.40; 95% confidence interval [CI], 1.01 to 1.95) while ex
      smokers did not exhibit increased risk compared with nonsmokers (adjusted RR,
      0.94; 95% CI, 0.7 to 1.3). Also, subjects with ETS exposure used significantly
      more hospital-based asthma care than those without ETS exposure (RR, 2.34; 95%
      CI, 1.80 to 3.05). CONCLUSIONS: Direct or environmental tobacco exposure
      prospectively predicted increased health-care utilization for asthma and reduced
      QOL in patients with asthma. These findings add to our existing knowledge of the
      detrimental effects of tobacco smoke and are of relevance specifically to
      patients with asthma.

PMID- 10084478
TI  - Eosinophilic inflammation in the airway is related to glucocorticoid
      reversibility in patients with pulmonary emphysema.
AB  - STUDY OBJECTIVES: We examined the effects of glucocorticoids on airway
      inflammation and its association with the reversibility of airflow obstruction in
      response to oral glucocorticoid administration in patients with COPD. PATIENTS:
      Twenty-four male patients with smoking-related stable pulmonary emphysema without
      alpha1-antitrypsin deficiency and nine normal healthy volunteers. MEASUREMENTS:
      We measured the pulmonary function, the inflammatory cells, and the levels of
      eosinophil cationic protein (ECP), immunoreactive neutrophil elastase-alpha1
      protease inhibitor (NE-alpha1-PI) complex, and interleukin (IL)-8 in sputum
      induced from patients with pulmonary emphysema in its stable phase before and
      after treatment with 20 mg oral prednisolone per day for 2 weeks. RESULTS: The
      eosinophil and neutrophil counts and the concentrations of ECP, NE-alpha1-PI
      complex, and IL-8 in the sputum were significantly increased at baseline. The
      eosinophil count at baseline was significantly correlated with the reversibility
      of airflow obstruction following treatment, and the treatment also significantly
      reduced the eosinophil numbers and ECP level in the sputum. In contrast, the
      increased neutrophil number and the concentrations of NE-alpha1-PI complex and IL
      8 at baseline did not correlate with the reversibility and were not affected by
      treatment. CONCLUSIONS: These findings suggest that the eosinophilic
      inflammation, not neutrophilic inflammation, in the airway is involved in the
      reversible part of the airflow obstruction in response to glucocorticoids in
      patients with pulmonary emphysema.

PMID- 10084479
TI  - Analysis of inhaled corticosteroid and oral theophylline use among patients with
      stable COPD from 1987 to 1995.
AB  - STUDY OBJECTIVE: To document temporal usage trends for commonly used respiratory
      medications in patients with COPD. DESIGN: We retrospectively evaluated baseline
      concomitant medications of 3,720 patients with COPD enrolled in 10 bronchodilator
      clinical trials from 1987 to 1995. The proportion of patients in each trial using
      inhaled corticosteroids, inhaled beta-adrenergics, inhaled anticholinergics, oral
      theophylline, and oral corticosteroids was analyzed using the Cochran-Armitage
      trend test. PATIENTS: All patients had stable, moderate-to-severe COPD without
      evidence of asthma or atopy. Reversibility to beta3-agonists was not a
      requirement. RESULTS: The percentage of patients using inhaled corticosteroids
      increased significantly over time (p < 0.001) from 13.2% in 1987 to 41.4% in
      1995. The percentage of patients receiving oral theophylline decreased
      significantly (p < 0.001) over this same time interval (63.4 to 29.0%). In
      addition, the percentage of patients using oral corticosteroids and the
      percentage using oral beta-adrenergics decreased moderately (p < 0.05) (30.1 to
      16.4% and 11.7 to 4.5%, respectively); the percentage of patients using inhaled
      anticholinergics increased slowly (p < 0.05) (48.2 to 53.8%). The percentage of
      patients receiving inhaled beta-adrenergics did not significantly (p > 0.05)
      change. CONCLUSIONS: The observed changes in use of inhaled corticosteroids and
      theophylline were not likely related to differences in disease severity or other
      patient characteristics in the evaluated trials, but related to changing
      prescribing and COPD management practices.

PMID- 10084480
TI  - Elevated O2 cost of ventilation contributes to tissue wasting in COPD.
AB  - BACKGROUND AND OBJECTIVES: Thirty to 50% of all COPD patients experience tissue
      wasting that may be caused by hypermetabolism, but the cause of the perturbed
      metabolic state is unclear. We hypothesized that the elevated O2 cost of
      ventilation (O2 COV) may be a contributing factor. All of the data are presented
      as means (+/-SEM). Ten hypoxemic (a PaO2 of 54+/-3 mm Hg) stable COPD patients
      (an FEV1/FVC ratio of 42+/-4%) and five healthy control subjects were studied.
      The patients were divided into two groups based on nutritional status. Group 1 (n
      = 6) was malnourished (a body mass index [BMI] of 17.6+/-0.7 kg/m2), and group 2
      (n = 4) was normally nourished (a BMI of 26.0+/-3 kg/m2). The O2 COV was
      determined by measuring the change in the oxygen consumption (VO2) and the minute
      ventilation (VE) caused by CO2-induced hyperventilation. RESULTS AND CONCLUSIONS:
      Group 1 had an elevated O2 COV when compared to group 2 and the control group,
      respectively: 16.4+/-1.0 vs 9.7+/-1.0 and 2.4+/-0.2 mL O2/L of VE (p < 0.05). The
      VO2 at rest was higher for group 1 than for group 2 and the control group,
      respectively: 4.5+/-0.3 vs 3.1+/-0.5 and 3.4+/-0.2 mL/kg/min (p < 0.05). The
      resting energy expenditure (REE) % predicted for group 1 was also higher than
      group 2 and the control group, respectively: 125+/-3% vs 87+/-7% and 97+/-2% (p <
      0.05). Significant correlations were observed that implicate the increased O2 COV
      as a cause of tissue wasting: O2 COV vs BMI (r = -0.79; p = 0.007), O2 COV vs REE
      % predicted (r = 0.66; p = 0.039), and REE % predicted vs BMI (r = -0.83; p =
      0.003). The O2 COV was also correlated with lung function: FEV1/FVC vs O2 COV (r
      = -0.84; p = 0.002). We conclude that in these COPD patients the O2 COV is
      associated with an increased metabolic rate which, in turn adversely affects the
      nutritional status.

PMID- 10084481
TI  - Detection of brain metastasis in potentially operable non-small cell lung cancer:
      a comparison of CT and MRI.
AB  - STUDY OBJECTIVE: To compare the usefulness of MRI and CT in the detection of
      brain metastases during preoperative evaluation and postoperative follow-up.
      DESIGN: A prospective and sequential comparison. PATIENTS AND METHODS: Of 332
      patients with potentially operable non-small cell lung cancer who were free of
      neurologic signs and symptoms, brain CT was performed preoperatively on 155
      patients (CT group) and brain MRI on 177 patients (MRI group). Patient
      characteristics in both groups were comparable. In 279 patients with complete
      resection of the primary lung tumor, intensive follow-up with CT and MRI was
      performed in the respective groups. The preoperative detection of brain
      metastases, postoperative intracranial recurrence rates, and characteristics of
      detected brain tumors were compared between the two groups. The survival of
      patients with brain metastases was also compared. RESULTS: From the first
      evaluation to 12 months after surgery for primary lung cancer, brain metastases
      were observed in 11 patients (7.1%) from the CT group and 12 patients (6.8%) from
      the MRI group. MRI detected brain metastases preoperatively in 6 of the 12
      patients (3.4% of the total MRI group), whereas CT detected brain metastases
      preoperatively in 1 of the 11 patients (0.6% of the total CT group). MRI showed a
      tendency toward a higher preoperative detection rate of brain metastases than CT
      (p = 0.069). Furthermore, the mean (+/- SD) maximal diameter of the brain
      metastases was significantly smaller in the MRI group (12.8+/-9.1 mm) than in the
      CT group (20.3+/-7.0 mm) (p = 0.041). However, the median survival time and 2
      year survival rate after treatment of detected brain metastases, respectively,
      were 10 months and 27% in the CT group and 17 months and 28% in the MRI group.
      There was no significant difference between the groups in survival time.
      CONCLUSIONS: Preoperative evaluation and intensive follow-up with MRI could
      facilitate early detection of brain metastases in patients with potentially
      operable lung cancer. However, further studies on detection and treatment of the
      metastatic tumors are considered necessary.

PMID- 10084482
TI  - Miss rate of lung cancer on the chest radiograph in clinical practice.
AB  - STUDY OBJECTIVES: To investigate the miss rate of non-small cell lung cancer
      (NSCLC) on the chest radiograph. In addition, the characteristics, the delay in
      diagnosis, and the change in prognosis of the missed lesions were studied.
      DESIGN: A retrospective study on patients with histopathologically proven NSCLC
      during the years 1992 through 1995 in a large community hospital. SETTING:
      Department of Radiology, Atrium Medical Center, Heerlen, the Netherlands.
      PATIENTS: During the study period, 495 patients presented with NSCLC. Of these
      patients, the complete set of chest radiographs was available for analysis in
      396; there were 300 men and 96 women, with a mean age of 68 years. MAIN OUTCOME
      MEASURES: The main outcome measures included the miss rate of NSCLC presenting as
      nodular lesions. Location, diameter, superposing structures, and delay of missed
      and detected lesions and the change of prognosis as a consequence of the delay in
      diagnosis were other measures. RESULTS: In 49 (19%) of 259 patients with NSCLC
      presenting as a nodular lesion on the chest radiographs, the lesions were missed.
      The miss rate was not dependent on location. Superposing structures were more
      often present in the group of missed lesions than in the group of detected
      lesions, respectively, 71% and 2%. The median diameter of the missed lesions was
      16 mm and of the detected lesions it was 40 mm. The median delay of the missed
      lesions was 472 days and of the detected lesions it was 29 days. Twenty-two (45%)
      patients with missed lesions remained in stage T1, 6 (12%) remained in stage T2
      and in 21 patients (43%), the tumor stage changed from stage T1 into T2.
      CONCLUSION: The miss rate of 19% in our study is low compared with the rate in
      the literature but it has a definitive impact on prognosis.

PMID- 10084483
TI  - Do Australian family physicians screen smokers for lung cancer?
AB  - STUDY OBJECTIVES: To determine family physicians' perceptions of the
      effectiveness of chest radiographs (CXRs) in reducing premature mortality from
      lung cancer and their self-reported levels of screening asymptomatic heavy
      smokers. DESIGN: National postal survey of 1,271 family physicians, obtaining 855
      completed questionnaires (67% response rate). SETTING AND PARTICIPANTS: Random
      sample of Australian family physicians. MEASUREMENTS AND RESULTS: One in five (n
      = 169, 20%) indicated that an annual CXR was an effective screening test. Older
      physicians were significantly more likely to hold this view (p < 0.0001). Nearly
      25% (n = 190, 22.5%) reported that they recommend an annual CXR as a screening
      test for asymptomatic heavy smokers. Three variables independently predicted such
      a practice: increasing physician age (p = 0.0085), being in solo practice (p =
      0.0068), and the aforementioned belief in its effectiveness (p < 0.0001).
      CONCLUSIONS: A substantial minority of family physicians recommends an annual CXR
      as a screening test despite contradictory evidence from randomized controlled
      trials. These significant variations in the absence of epidemiologic evidence
      invite further research to develop effective, efficient, and affordable
      preventive care in family practice.

PMID- 10084484
TI  - Intrapleural streptokinase in the management of malignant multiloculated pleural
      effusions.
AB  - OBJECTIVE: Pleural effusions are a frequent complication of malignancy and cause
      considerable morbidity from dyspnea. The drainage and control of malignant
      effusions relieve symptoms and maintain quality of life but these are difficult
      in patients with multiloculated effusions in whom drainage usually fails. This
      observational series reports the use of intrapleural streptokinase (IPSK) in the
      management of malignant multiloculated pleural effusions resistant to standard
      chest tube drainage. METHODS: Ten consecutive patients with malignant
      multiloculated pleural effusions, aged 39 to 89 years, were given 250,000-IU
      doses of IPSK twice daily after failure to drain the effusions with a standard
      chest tube because of multiloculation and multiseptation, as demonstrated by CT
      or ultrasound scanning. Outcome was assessed by radiographic improvement and
      symptom control. RESULTS: All 10 patients responded to between 500,000 and
      1,500,000 IU of streptokinase. There was an increase in pleural fluid drained
      (mean volume+/-SD; pre-IPSK, 843+/-690 mL; post-IPSK, 2,368+/-1,051 mL; p <
      0.001, paired t test), and radiographic improvement was seen in all 10 patients.
      All subjects tolerated the instillation of streptokinase well. One subject
      required opiate analgesia for transient chest pain, and there were no hemorrhagic
      or allergic complications. One patient died of unrelated septicemia. CONCLUSIONS:
      This series suggests that IPSK may be useful in the drainage of malignant
      multiloculated pleural effusions in patients who fail to drain adequately with a
      standard chest tube. Malignant pleural effusions should not be considered a
      contraindication to IPSK.

PMID- 10084485
TI  - Pulmonary cryptococcosis in patients without HIV infection.
AB  - PURPOSE: To further elucidate the diagnostic and therapeutic approaches to
      patients with pulmonary cryptococcosis who are not HIV-infected. SUBJECTS: All of
      the patients without HIV infection who received care at two Midwest hospitals
      between January 1986 and February 1996 and had a respiratory isolate of
      Cryptococcus neoformans. METHODS: The medical records of the study patients were
      reviewed for demographic data, host immune status, respiratory symptoms,
      diagnostic studies, treatment, and follow-up. RESULTS: Forty-two patient
      presentations comprised the overall study group. Thirty-six patients (85.7%) had
      no evidence of dissemination, and six patients (14.3%) had disseminated disease.
      Seven of the 36 patient presentations were definitive pulmonary cryptococcosis,
      15 were presumptive disease, and 14 were colonization with C neoformans. Neither
      the baseline demographic parameters nor the immune status appeared to
      discriminate the patients with disease from the patients with colonization. A
      serum cryptococcal antigen (sCRAG) was positive for 7 of 18 patients, 3 of whom
      were proven by culture to have a disseminated infection. A negative sCRAG was
      observed in 11 patients, one of whom had proven dissemination. Fifteen patients
      underwent a lumbar puncture as part of their evaluation, and cryptococcal
      meningitis was diagnosed in three of these patients, all of whom had positive
      blood cultures for C neoformans. The majority of the patients did not receive
      antifungal therapy. CONCLUSION: In the majority of the patients, the lung
      appeared to be the sole organ involved, and a workup for systemic infection was
      rarely helpful. A positive sCRAG was not specific for dissemination. Antifungal
      therapy should be reserved for symptomatic patients, for patients with a positive
      sCRAG, and for patients with underlying immunosuppression.

PMID- 10084486
TI  - Mycobacterial infections in lung transplant recipients.
AB  - BACKGROUND: Immunosuppression and chronic lung disease are known risk factors for
      mycobacterial infection and might be expected to develop with an increased
      frequency in lung transplant recipients. We therefore sought to document the
      incidence and type of mycobacterial infections in a large lung transplant
      program. METHODS: A retrospective review of 219 transplant procedures (60 single
      lung transplants and 159 double lung transplants) in 210 patients was conducted.
      All patients had scheduled surveillance bronchoscopies at 3, 6, 9, 12, 18, and 24
      months, and yearly thereafter. BAL samples were processed routinely for
      mycobacterium. RESULTS: Eight patients (3.8%) had evidence of infection (5 men, 3
      women; age range, 26 to 63 years). The reasons for transplant were obstructive
      lung disease (six), cystic fibrosis (one), and pulmonary fibrosis (one). Five
      recipients had infection in their native lungs; two of five cultured
      mycobacterium from BAL following transplantation. At least four of five patients
      had nontuberculous mycobacterium (one showed acid fast bacilli and granuloma on a
      biopsy specimen that was not sent for culture). None of the five developed
      disease (mean follow-up = 22 months; range, 3 to 30 months). The organisms were
      Mycobacterium avium complex (three), Mycobacterium xenopi (one), and unidentified
      (one). Of the three remaining patients who developed infection after
      transplantation, one grew Mycobacterium chelonae and the others grew
      Mycobacterium tuberculosis (both received double lung transplants and had no
      evidence of mycobacterium in their native lungs). The only definite symptomatic
      disease occurred in the patients with M tuberculosis, one of whom had evidence of
      dissemination. The patients with M tuberculosis responded to standard treatment.
      There have been no deaths due to mycobacterium. CONCLUSION: Mycobacterial disease
      rarely occurs following lung transplantation. Cultures for mycobacterium in
      surveillance BALs in the absence of symptoms are likely unnecessary.

PMID- 10084487
TI  - Factors predicting mortality of patients with lung abscess.
AB  - BACKGROUND: The rates of morbidity and mortality associated with lung abscess are
      still significant despite the introduction of antibiotic treatments. The aim of
      this work was to identify the factors that predict a poor outcome for patients
      with lung abscess. METHODS: We retrospectively reviewed the records and the
      roentgenographic files of adult patients with lung abscess who were hospitalized
      from 1980 to 1996 at the Hadassah University Hospital, in Jerusalem, Israel.
      RESULTS: The study population comprised 75 patients, and the mean age was 52
      years old (range, 12 to 89 years). The mean (+/- SD) hospitalization duration was
      25.7+/-21.5 days (range, 5 to 94 days). Fifteen patients (20%) succumbed to the
      infection. The patients who died had more predisposing factors (+/-SD), such as
      pneumonia, neoplasm, and altered consciousness, than those who survived,
      respectively: 2.73+/-1.4 vs 1.9+/-1.3 (p < 0.03). The patients with anemia on
      admission (hemoglobin levels of < 10 g/dL) had a higher mortality rate than those
      with higher hemoglobin levels, respectively: 58.3 vs 12.9% (p = 0.0008). A higher
      mortality rate was also associated with infection by Pseudomonas aeruginosa
      (83%), Staphylococcus aureus (50%), and Klebsiella pneumoniae (44%). The patients
      who died had larger abscess volumes (+/-SD) than those who survived (233+/-99 vs
      157+/-33 mL), although it did not reach statistical significance. The diameter of
      the abscess correlated with the hospitalization time (r = 0.5; p < 0.001).
      CONCLUSION: High rates of morbidity and mortality are associated with lung
      abscess despite appropriate antibiotic therapy and better supportive care. In
      patients with several predisposing factors, such as a large abscess size and a
      right-lower-lobe location, the prognosis was worse. The patients infected with S
      aureus, K pneumoniae, and particularly P aeruginosa had an ominous prognosis. As
      the prognosis for lung abscess has not improved sufficiently since the
      introduction of antibiotics, other modalities should be considered for patients
      with poor prognostic signs.

PMID- 10084488
TI  - Predicting factors for outcome of tube thoracostomy in complicated parapneumonic
      effusion for empyema.
AB  - STUDY OBJECTIVES: To determine the predicting factors for outcome of tube
      thoracostomy in patients with complicated parapneumonic effusion (CPE) or
      empyema. DESIGN AND SETTINGS: Retrospective chart review over a 55-month period
      at a tertiary referred medical center. PATIENTS AND MEASUREMENTS: The medical
      charts of patients with empyema or CPE were reviewed. Data including age, gender,
      clinical symptoms, important underlying diseases, leukocyte count, duration of
      preadmission symptoms, interval from first procedure to second procedure, the
      time from first procedure to discharge (recovery time), the amount of effusion
      drained, administration of intrapleural streptokinase, chest tube size and
      position, loculation of pleural effusion, and characteristics and culture results
      of pleural effusion were recorded and compared between groups of patients with
      successful and failed outcome of tube thoracostomy drainage. RESULTS: One hundred
      twenty-one patients were selected for study. One hundred of these patients had
      received tube thoracostomy drainage with 53 successful outcomes and 47 failed
      outcomes of chest tube drainage. Nineteen patients received decortication
      directly, and the other two received antibiotics alone. Univariate analysis
      showed that pleural effusion leukocyte count, effusion amount, and loculation of
      pleural effusion were significantly related to the outcome of chest tube
      drainage. Multiple logistic regression analysis demonstrated that loculation and
      pleural effusion leukocyte count < or = 6,400/uL were the only independent
      predicting factors related to failure of tube thoracostomy drainage. CONCLUSIONS:
      Loculation and pleural effusion leukocyte count < or = 6,400/microL were
      independent predicting factors of poor outcome of tube thoracostomy drainage.
      These results suggest that if the initial attempt at chest tube drainage fails,
      early surgical intervention should be considered in good surgical candidates with
      loculated empyema or pleural effusion with leukocyte count < or = 6,400/microL.

PMID- 10084489
TI  - Site of pleural drain insertion and early postoperative pulmonary function
      following coronary artery bypass grafting with internal mammary artery.
AB  - STUDY OBJECTIVES: Coronary artery bypass graft (CABG) surgery using the left
      internal mammary artery (LIMA) impairs postoperative pulmonary function. We
      studied the changes in pulmonary function and subjective pain relative to the
      site of chest tube insertion. DESIGN: Thirty patients undergoing CABG surgery
      using the LIMA were randomized into two groups. Group A (n = 15) received a left
      chest tube inserted from the midline (subxyphoid). Group B (n = 15) had a tube
      placed in the sixth intercostal space at the anterior axillary line. All of the
      patients underwent bedside pulmonary function testing preoperatively and on
      postoperative days (PODs) 1, 3, and 5. Pain sensation was quantified by a
      standardized score (1 to 10). RESULTS: A significant impairment of pulmonary
      function parameters was observed in both groups until POD 5. For group A, the
      decline in percent predicted (+/-SD) in the vital capacity (VC) from before
      surgery to POD 5 was, respectively, 92.3+/-30.6% to 56.9+/-12.6% (p < 0.001). For
      group B, the decline in the VC was from 88.0+/-18.2% to 55.5+/-14.8% (p < 0.001).
      The FEV1 declined concomitantly in group A from 86.2+/-18.2% to 50.8+/-12.1%, and
      in group B from 83.5+/-16.4% to 53.9+/-12.5% (p < 0.001). On POD 1, a
      significantly lower decrease in the VC was measured in group A than in group B,
      respectively: 45.3+/-15.5% vs 28.6+/-8.7% (p < 0.001). A significantly lower
      decrease in the FEV1 was also seen in group A than in group B, respectively:
      36.9+/-12.9% vs 28.0+/-10.6% (p < 0.05). Pain experienced during deep inspiration
      was also significantly less in group A than in group B, respectively: 1.2+/-1.1
      vs 2.5+/-0.9 (p < 0.01). CONCLUSIONS: Subxyphoid insertion of the pleural drain
      leads to a significantly lower impairment of pulmonary function and less
      subjective pain than insertion at the intercostal position. The drainage of the
      left pleural space is equally effective with both techniques.

PMID- 10084490
TI  - The snoring spectrum: acoustic assessment of snoring sound intensity in 1,139
      individuals undergoing polysomnography.
AB  - STUDY OBJECTIVES: To quantify the snoring sound intensity levels generated by
      individuals during polysomnographic testing and to examine the relationships
      between acoustic, polysomnographic, and clinical variables. DESIGN: The
      prospective acquisition of acoustic and polysomnographic data with a
      retrospective medical chart review. SETTING: A sleep laboratory at a primary care
      hospital. PARTICIPANTS: All 1,139 of the patients referred to the sleep
      laboratory for polysomnographic testing from 1980 to 1994. INTERVENTIONS: The
      acoustic measurement of snoring sound intensity during sleep concurrent with
      polysomnographic testing. MEASUREMENTS AND RESULTS: Four decibel levels were
      derived from snoring sound intensity recordings. L1, L5, and L10 are measures of
      the sound pressure measurement in decibels employing the A-weighting network that
      yields the response of the human ear exceeded, respectively, for 1, 5, and 10% of
      the test period. The Leq is a measure of the A-weighted average intensity of a
      fluctuating acoustic signal over the total test period. L10 levels above 55 dBA
      were exceeded by 12.3% of the patients. The average levels of snoring sound
      intensity were significantly higher for men than for women. The levels of snoring
      sound intensity were associated significantly with the following:
      polysomnographic testing results, including the respiratory disturbance index
      (RDI), sleep latency, and the percentage of slow-wave sleep; demographic factors,
      including gender and body mass; and clinical factors, including snoring history,
      hypersomnolence, and breathing stoppage. Men with a body mass index of > 30 and
      an average snoring sound intensity of > 38 dBA were 4.1 times more likely to have
      an RDI of > 10. CONCLUSIONS: Snoring sound intensity levels are related to a
      number of demographic, clinical, and polysomnographic test results. Snoring sound
      intensity is closely related to apnea/hypopnea during sleep. The noise generated
      by snoring can disturb or disrupt a snorer's sleep, as well as the sleep of a bed
      partner.

PMID- 10084491
TI  - Positional treatment vs continuous positive airway pressure in patients with
      positional obstructive sleep apnea syndrome.
AB  - OBJECTIVES: The aim of this study was to compare the relative efficacy of
      continuous positive airway pressure (CPAP) and positional treatment in the
      management of positional obstructive sleep apnea (OSA), using objective outcome
      measures. DESIGN: A prospective, randomized, single blind crossover comparison of
      CPAP and positional treatment for 2 weeks each. SETTING: A university teaching
      hospital. PATIENTS: Thirteen patients with positional OSA, aged (mean+/-SD) 51+/
      9 years, with an apnea-hypopnea index (AHI) of 17+/-8. MEASUREMENTS: (1) Daily
      Epworth Sleepiness Scale scores; (2) overnight polysomnography, an objective
      assessment of sleep quality and AHI; (3) maintenance of wakefulness testing; (4)
      psychometric test battery; (5) mood scales; (6) quality-of-life questionnaires;
      and (7) individual patient's treatment preference. RESULTS: Positional treatment
      was highly effective in reducing time spent supine (median, 0; range, 0 to 32
      min). The AHI was lower (mean difference, 6.1; 95% confidence interval [CI], 2 to
      10.2; p = 0.007), and the minimum oxygen saturation was higher (4%; 95% CI, 1% to
      8%; p = 0.02) on CPAP as compared with positional treatment. There was no
      significant difference, however, in sleep architecture, Epworth Sleepiness Scale
      scores, maintenance of wakefulness testing sleep latency, psychometric test
      performance, mood scales, or quality-of-life measures. CONCLUSION: Positional
      treatment and CPAP have similar efficacy in the treatment of patients with
      positional OSA.

PMID- 10084492
TI  - Timing of referral for lung transplantation for cystic fibrosis: overemphasis on
      FEV1 may adversely affect overall survival.
AB  - STUDY OBJECTIVES: (1) Report our experience with referral for lung
      transplantation. (2) Review survival in cvstic fibrosis (CF) patients without
      lung transplantation after FEV1 remains < 30% predicted for 1 years. DESIGN:
      Retrospective review. SETTING: A university hospital CF center. PATIENTS: (1)
      Forty-five patients referred for lung transplantation evaluation, and (2) 178
      patients without Burkholderia sp infection, with the above FEVl criterion. MAIN
      OUTCOME MEASURE: Survival. MEASUREMENTS AND RESULTS: (1) One- and 2-year survival
      after transplantation was 55% and 45%, respectively. However, among patients
      without transplants with FEVl < 30% predicted, median survival, 1986 to 1990, ie,
      before the transplant era, was 4.6 years with 25% living > 9 years (before 1986,
      25% lived > 6 vears). (2) Survival after transplantation was not correlated to
      any of the following: age, sex, genotype, FEVI percent predicted, insulin
      dependent diabetes mellitus, or with waiting time before transplantation, and did
      not seem to be correlated to serum bicarbonate or percent ideal body weight. Four
      of five patients already infected with Burkholderia species died within 5 months
      of transplantation; the fifth died at 17 months. All five died of pulmonary or
      extrapulmonarv infection with Burkholderia species CONCLUSIONS: Use of FEV! < 30%
      predicted to automatically establish transplantation eligibility could lead to
      decreased overall survival for CF patients. Referral for evaluation and
      transplantation should also be based on oxygen requirement, rate of
      deterioration, respiratory microbiology, quality of life, frequency of IV
      antibiotic therapy, and other considerations. If pulmonary status has
      unexpectedly improved when the patient is at or near the top of the waiting list,
      total survival may be improved by "inactivating the patient" until progression is
      again evident.

PMID- 10084493
TI  - Gender differences in the oxygen transport system during maximal exercise in
      hypertensive subjects.
AB  - STUDY OBJECTIVES: To analyze gender differences in the oxygen transport system at
      peak exercise with particular emphasis on the difference in systemic
      arteriovenous oxygen extraction and in mixed venous oxygen saturation. PATIENTS
      AND METHODS: Cardiopulmonary graded exercise testing and hemodynamic assessment
      were performed on a cycle ergometer in 64 hypertensive patients (32 female and 32
      male) varying in age from 23 to 64 years. Female and male patients were matched
      for age and BP. MEASUREMENTS AND RESULTS: Peak oxygen uptake was significantly
      lower in women than in men, and when expressed in absolute units (L/min: -39%)
      and when normalized for body mass (mL/min/kg: -33%) or statistically adjusted for
      height and weight (-29%). This resulted essentially from a significantly lower
      cardiac output in women, both when expressed in absolute units and when adjusted
      for body size. At the peripheral level, female patients had a lower arteriovenous
      oxygen content difference at peak exercise, which resulted from a lower
      hemoglobin concentration and the inability to decrease mixed venous oxygen
      saturation to the same level as in men. CONCLUSION: The lower peak oxygen uptake
      of women results from both central and peripheral factors. The significantly
      higher value for mixed venous oxygen saturation, which contributes to the lower
      arteriovenous oxygen difference of women, could result from their smaller muscle
      mass, lower capillary density, and lower oxidative potential.

PMID- 10084494
TI  - Community-wide assessment of intensive care outcomes using a physiologically
      based prognostic measure: implications for critical care delivery from Cleveland
      Health Quality Choice.
AB  - STUDY OBJECTIVES: To examine the applicability of a previously developed
      intensive care prognostic measure to a community-based sample of hospitals, and
      assess variations in severity-adjusted mortality across a major metropolitan
      region. DESIGN: Retrospective cohort study. SETTING: Twenty-eight hospitals with
      38 ICUs participating in a community-wide initiative to measure performance
      supported by the business community, hospitals, and physicians. PATIENTS:
      Included in the study were 116,340 consecutive eligible patients admitted to
      medical, surgical, neurologic, and mixed medical/surgical ICUs between March 1,
      1991, and March 31, 1995. MAIN OUTCOME MEASURES: The risk of hospital mortality
      was assessed using a previous risk prediction equation that was developed in a
      national sample, and a reestimated logistic regression model fit to the current
      sample. The standardized mortality ratio (SMR) (actual/predicted mortality) was
      used to describe hospital performance. RESULTS: Although discrimination of the
      previous national risk equation in the current sample was high (receiver
      operating characteristic [ROC] curve area = 0.90), the equation systematically
      overestimated the risk of death and was not as well calibrated (Hosmer-Lemeshow
      statistic, 2407.6, 8 df, p < 0.001). The locally derived equation had similar
      discrimination (ROC curve area = 0.91), but had improved calibration across all
      ranges of severity (Hosmer-Lemeshow statistic = 13.5, 8 df, p = 0.10). Hospital
      SMRs ranged from 0.85 to 1.21, and four hospitals had SMRs that were higher or
      lower (p < 0.01) than 1.0. Variation in SMRs tended to be greatest during the
      first year of data collection. SMRs also tended to decline over the 4 years
      (1.06, 1.02, 0.98, and 0.94 in years 1 to 4, respectively), as did mean hospital
      length of stay (13.0, 12.4, 11.6, and 11.1 days in years 1 to 4; p < 0.001).
      However, excluding the increasing (p < 0.001) number of patients discharged to
      skilled nursing facilities attenuated much of the decline in standardized
      mortality over time. CONCLUSIONS: A previously validated physiologically based
      prognostic measure successfully stratified patients in a large community-based
      sample by their risk of death. However, such methods may require recalibration
      when applied to new samples and to reflect changes in practice over time.
      Moreover, although significant variations in hospital standardized mortality were
      observed, changing hospital discharge practices suggest that in-hospital
      mortality may no longer be an adequate measure of ICU performance. Community-wide
      efforts with broad-based support from business, hospitals, and physicians can be
      sustained over time to assess outcomes associated with ICU care. Such efforts may
      provide important information about variations in patient outcomes and changes in
      practice patterns over time. Future efforts should assess the impact of such
      community-wide initiatives on health-care purchasing and institutional quality
      improvement programs.

PMID- 10084495
TI  - Comparison of outcome from intensive care admission after adjustment for case mix
      by the APACHE III prognostic system.
AB  - STUDY OBJECTIVES: To evaluate the acute physiology, age, chronic health
      evaluation III (APACHE III) scoring system in the context of general adult ICUs
      in the United Kingdom. DESIGN: Prospective, noninterventional, cohort study.
      SETTING: Seventeen general adult ICUs in a discrete area of southwest England.
      PATIENTS: 12,793 patients admitted between April 1, 1993 and December 31, 1995.
      MEASUREMENTS: Sociodemographic and severity-of-illness data were collected for
      all patients admitted to the study units. Formal goodness-of-fit tests were
      applied and observed mortality was compared with that predicted by using the
      APACHE III system. RESULTS: For the group of ICUs as a whole, the risk-adjusted
      standardized mortality ratio (SMR) was 1.23 (95% confidence intervals, 1.12
      1.25). For 11 out of 17 ICUs, the SMR was significantly greater than unity (p <
      0.05). Calibration, as tested by Hosmer-Lemeshow statistics, was poor (H2 =
      312.54; C2 = 332.85; df = 8; p < 0.01); however, model discrimination was good
      with a total correct classification rate of 82.9% and an area under the receiver
      operating characteristic curve of 0.89. CONCLUSIONS: The excess mortality
      observed after case-mix adjustment using the APACHE III system in this study may
      be the result of either poor intensive care performance as compared with the
      United States or a failure of the APACHE III equation to fit the UK data.

PMID- 10084496
TI  - The utility of open lung biopsy in patients requiring mechanical ventilation.
AB  - STUDY OBJECTIVE: To determine the diagnostic yield, morbidity, mortality, and
      therapeutic impact of the open lung biopsy in patients requiring mechanical
      ventilation. DESIGN: Retrospective review of patient records. SETTING: Tertiary
      ICU. PATIENTS: Patients with respiratory failure and diffuse pulmonary
      infiltrates requiring mechanical ventilation, leading up to or following an open
      lung biopsy. MEASUREMENTS: Information included patient demographics, organ
      failure, microbiological results before open-lung biopsy, Pao,/fraction of
      inspired oxygen values before and after biopsy, immunosuppression, timing of open
      lung biopsy, biopsy-related morbidity and mortality, duration of after-biopsy
      ventilation, open lung biopsy results, biopsy-initiated treatment alterations,
      and hospital outcome. RESULTS: Twenty-four patients were identified. The mean age
      was 48.9 years (confidence interval, 42.1 to 55.7). Twenty-one percent had
      respiratory infections diagnosed before open lung biopsy but not confirmed by
      open lung biopsy. Intraoperative complications occurred in 21% of patients, and
      postoperative complications occurred in 17% of patients. Operative mortality was
      8.4%. The specific and the nonspecific diagnostic rates were both 46%. Lung
      histology was normal in two patients; one of those patients had a false-negative
      finding. No patient with respiratory failure plus 2 2 other organ failures
      survived. Alteration of therapy did not differentiate between survivors. Open
      lung biopsy-guided alteration of therapy directly benefited 39%, and withdrawal
      was possible in 8.4% of the patients. CONCLUSIONS: The multiple organ dysfunction
      score should be considered when deciding the relative risk of performing an open
      lung biopsy, which in this group of patients provided a specific diagnosis in 46%
      and carried a mortality rate of 8.4%.

PMID- 10084497
TI  - Venovenous extracorporeal life support via percutaneous cannulation in 94
      patients.
AB  - STUDY OBJECTIVE: The objective of this study was to demonstrate the safety and
      utility of a method of percutaneous access for cannulation of adult patients for
      venovenous extracorporeal life support (ECLS). DESIGN: A retrospective review of
      a patient series. SETTING: A surgical ICU at a university teaching hospital.
      PATIENTS: The study group consisted of 94 adults > 17 years old with respiratory
      failure who were placed on venovenous ECLS by means of percutaneous cannulation.
      INTERVENTIONS: The cannulation of the internal jugular and femoral veins (FVs)
      using the Seldinger technique for venovenous ECLS. MEASUREMENTS AND RESULTS:
      Between May 1992 and November 1997, we performed percutaneous cannulation for
      venovenous ECLS in 94 adult patients with respiratory failure. The mean (+/- SD)
      age was 36.1+/-12.7 years old (range, 17 to 65 years). The mean (+/-SD) weight
      was 80.7+/-22.3 kg (range, 36 to 156 kg). The right internal jugular vein (RIJV)
      was used for venous drainage access in all but four cases. The right FV (n = 86),
      the left FV (n = 3), or the RIJV (n = 4) was utilized for venous reinfusion. The
      maximum blood flow (+/-SD) during ECLS was 57.6+/-17.5 mL/kg/min (range, 22.4 to
      127.8 mL/kg/min), with a postmembrane outlet pressure (+/-SD) of 146+/-43 mm Hg
      (range, 56 to 258 mm Hg) at the maximum flow rate. There were 11 unsuccessful
      percutaneous cannulation attempts. In three patients (3%), the complications
      consisted of arterial injury requiring operative cutdown and repair. In six
      patients (6%), cannula-site bleeding required pursestring suture reinforcement of
      the cannula site. One patient died from the perforation of the superior vena cava
      during cannulation. CONCLUSIONS: Based on these data, we conclude that
      percutaneous cannulation may be utilized to provide venovenous ECLS in adults.

PMID- 10084498
TI  - Perfluorooctyl bromide (perflubron) stimulates mucin secretion in the ferret
      trachea.
AB  - OBJECTIVES: Partial liquid ventilation with perfluorooctyl bromide (perflubron)
      has been shown to be safe and effective in animal models with respiratory
      failure. However, airway mucus accumulation has been reported to be a problem in
      human trials. We hypothesized that this might be because perflubron directly
      affects mucociliary clearance or stimulates mucus secretion. METHODS AND RESULTS:
      We first measured the mucociliary transportability of secretions on the mucus
      depleted frog palate exposed to perflubron and demonstrated that the ciliated
      epithelium remained intact with preservation of mucociliary transport. We then
      measured mucin and lysozyme secretion from isolated ferret tracheal segments to
      evaluate the secretagogue potential of perflubron. There was an 86% increase in
      mucin secretion with perflubron incubation at 40 min (n = 19; p < 0.01) and a 52%
      increase after 4 h of exposure followed by evaporation of perflubron (n = 19; p <
      0.01). There was no significant difference in lysozyme secretion at any time
      between perflubron-exposed or buffer-exposed tissue (n = 4). The secretagogue
      effect was completely blocked by nordihydroguaiaretic acid, an inhibitor of
      arachidonic acid (AA) metabolism. CONCLUSION: These data suggest that although
      perflubron does not seem to be harmful to the airway, it induces mucus secretion
      in a noninflamed airway, and that this can be modulated by inhibitors of AA
      metabolism.

PMID- 10084499
TI  - Bacterial endotoxin is an active component of cigarette smoke.
AB  - BACKGROUND: Chronic bronchitis in cigarette smokers shares many clinical and
      histologic features with environmental lung diseases attributed to bacterial
      endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation
      mimics many of the acute effects of cigarette smoke in the lower airway.
      Therefore, we reasoned that LPS may be a biologically active component of
      cigarette smoke. DESIGN: The Limulus amebocyte lysate (LAL) assay was used to
      measure LPS in the tobacco and filter tip components of unsmoked 1R4F
      experimental cigarettes and commercially available "light" cigarettes, as well as
      in mainstream (MS) and sidestream (SS) smoke particles generated with an
      automated smoking machine and collected on ventilator mainflow filters. SETTING
      AND PARTICIPANTS: Blood LPS activity and plasma cytokine concentrations were
      measured in groups of healthy smokers and nonsmokers who reported to the walk-in
      clinic at the Baltimore VA Medical Center for unrelated complaints. MEASUREMENTS:
      Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis
      factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II
      (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay.
      RESULTS: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0
      microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips
      (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of
      cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64
      ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5
      ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of
      inhaled LPS may occur, we failed to detect any differences between nonsmokers and
      smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL,
      respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL,
      respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II
      (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p =
      0.20). CONCLUSIONS: Smoking one pack of cigarettes per day delivers a dose of
      respirable LPS that is comparable to the levels of LPS associated with adverse
      health effects in cotton textile workers. Thus, we suggest that the bioactive LPS
      in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that
      develops in susceptible cigarette smokers.

PMID- 10084500
TI  - Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine
      activation.
AB  - Chronic heart failure (CHF) is a complex syndrome affecting many body systems.
      Body wasting (ie, cardiac cachexia) is a serious complication of CHF long known
      but little investigated. Although no specific diagnostic criteria have been
      established, we have suggested that cardiac cachexia be defined on the basis of
      the presence of documented nonintentional and nonedematous weight loss > 7.5% of
      the premorbid normal weight, occurring over a time period of > 6 months. Using
      this definition, 16% of an unselected CHF outpatient population was found to be
      cachectic. The cachectic state is predictive of impaired prognosis independently
      of age, functional disease classification, left ventricular ejection fraction,
      and peak oxygen consumption. The mortality in the cachectic cohort is 50% at 18
      months. Analyzing body composition in detail, it has been found that patients
      with cardiac cachexia suffer from a general loss of fat tissue (ie, energy
      reserves), lean tissue (ie, skeletal muscle), and bone tissue (ie, osteoporosis).
      Cachectic CHF patients are weaker and fatigue earlier, which is due to both
      reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic
      alterations leading to cardiac cachexia remain unclear, but initial cross
      sectional studies have suggested that humoral neuroendocrine and immunologic
      abnormalities are linked, independently of established heart failure severity
      markers, to the presence of body wasting. Comparing the features of cachectic and
      noncachectic CHF patients with those of healthy control subjects, it is mainly
      the cachectic CHF patients who show raised plasma levels of epinephrine,
      norepinephrine, and cortisol; the highest plasma renin activity and aldosterone
      plasma concentrations; and the lowest plasma sodium level. Several studies have
      shown that cardiac cachexia is linked to raised plasma levels of tumor necrosis
      factor-ac. The degree of body wasting is strongly correlated with neurohormonal
      and immune abnormalities. The available evidence suggests that cardiac cachexia
      is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis.
      A complex imbalance of different body systems may cause the development of body
      wasting.

PMID- 10084501
TI  - A critical review of the studies of the effects of simulated or real
      gastroesophageal reflux on pulmonary function in asthmatic adults.
AB  - OBJECTIVE: To identify and critically review the published peer-reviewed, English
      language studies of the effects of both spontaneous and simulated
      gastroesophageal reflux (GER) on pulmonary function in asthmatic adults. DESIGN:
      Using the 1966 to 1997 MEDLINE database, the terms asthma and lung disease were
      combined with GER to identify studies of the effects of GER and acid perfusion
      (AP) of the esophagus on pulmonary function. The bibliographies were also
      reviewed. Studies of asthmatics with and without symptomatic GER were analyzed
      both together and separately. RESULTS: A total of 254 citations, including 180
      published in English, were identified. Among these were 18 studies of GER and AP
      in asthmatic adults. These reports, which contain data on 312 asthmatics, found
      that the FEV1 and the midexpiratory rate did not change during AP and GER in the
      studies containing 97% and 94% of the asthmatics, respectively. Flow volume loop
      indexes, including the flow at 50% of the vital capacity (V50), flow at 25% of
      the vital capacity, and the peak expiratory flow rate, did not change during AP
      or GER in the studies with 77%, 60%, and 65% of the asthmatics, respectively.
      Small changes in the resistance were reported in the studies containing 42% of
      the asthmatics. Among asthmatics without symptomatic GER, no changes in
      spirometry, resistance, and flow volume indexes were found, except for a 10%
      decline in V50 in one study with seven subjects. CONCLUSIONS: In asthmatics with
      GER, the effects of AP on pulmonary function are minimal, and only a minority are
      affected. The literature does not support the conclusion that asymptomatic reflux
      contributes to worsening lung function.

PMID- 10084502
TI  - The Swan-Ganz catheter: requesting scientific trials is not an "assault".

PMID- 10084503
TI  - The pulmonary artery catheter: nonexistential entity or occasionally useful tool?

PMID- 10084504
TI  - Indications for positive airway pressure treatment of adult obstructive sleep
      apnea patients: a consensus statement.
AB  - We developed a short-length document that clearly delineates a prudent approach
      to and criteria for reimbursement of positive airway pressure (PAP) costs for the
      treatment of obstructive sleep apnea (OSA). Treatment modalities for OSA with PAP
      include continuous positive airway pressure, bilevel or variable PAP, and
      autotitrating PAP. This guidance on the appropriate criteria for PAP use in OSA
      is based on widely acknowledged peer-reviewed studies and widely accepted
      clinical practice. These criteria reflect current opinion on the appropriate
      clinical management of OSA in lieu of data pending from the Sleep Heart Health
      Study and upcoming outcome studies. This document is not intended to provide a
      complete review and analysis of the OSA clinical literature. The key to the
      success of this document is to foster consensus within and outside the clinical
      sleep community by providing a common sense and easily understood approach to the
      treatment of OSA with PAP.

PMID- 10084505
TI  - Incidence of heart failure in 2,737 older persons with and without diabetes
      mellitus.
AB  - STUDY OBJECTIVES: To investigate in older persons whether diabetes mellitus is an
      independent risk factor for congestive heart failure (CHF). DESIGN: A prospective
      study was performed in 2,737 older persons investigating the incidence of new CHF
      in persons with and without diabetes mellitus. SETTING: A long-term health-care
      facility. PATIENTS: Eight hundred sixty-five men and 1,872 women, with a mean age
      of 81+/-9 years. MEASUREMENTS AND RESULTS: At 43-month follow-up, new CHF
      developed in 272 of 690 persons (39%) with diabetes mellitus and in 467 of 2,047
      persons (23%) without diabetes mellitus (p < 0.0001). Cox regression analysis
      showed that age (p = 0.0001, risk ratio = 1.048), hypertension (p = 0.0001, risk
      ratio = 2.524), coronary artery disease (p = 0.0001, risk ratio = 4.008), male
      gender (p = 0.0001, risk ratio = 1.399), and diabetes mellitus (p = 0.0003, risk
      ratio = 1.337) were significantly positively associated with the time to the
      development of CHF. CONCLUSIONS: Older persons with diabetes mellitus had a 1.3
      times higher chance of developing CHF than those without diabetes mellitus after
      controlling the confounding effects of other prognostic variables.

PMID- 10084506
TI  - How accurate is spirometry at predicting restrictive pulmonary impairment?
AB  - OBJECTIVE: To determine the accuracy with which spirometric measurements of FVC
      and expiratory flow rates can diagnose the presence of a restrictive impairment.
      DESIGN: The pulmonary function tests of 1,831 consecutive white adult patients
      who had undergone both spirometry and lung volume measurements on the same visit
      over a 2-year period were analyzed. The probability of restrictive pulmonary
      impairment, defined as a reduced total lung capacity (TLC) below the lower limit
      of the 95% confidence interval, was determined for each of several categoric
      classifications of the spirometric data, and additionally for each of several
      interval levels of the FVC and the FEV1/FVC ratio. SETTING: A large clinical
      laboratory in a university teaching hospital using quality-assured and
      standardized spirometry and lung volume measurement techniques according to
      American Thoracic Society standards. RESULTS: Two hundred twenty-five of 1,831
      patients (12.3%) had a restrictive defect. The positive predictive value of
      spirometry for predicting restriction was relatively low; of 470 patients with a
      low FVC on spirometry, only 41% had restriction confirmed on lung volume
      measurements. When the analysis was confined to the 264 patients with a
      restrictive pattern on spirometry (ie, low FVC and normal or above normal
      FEV1/FVC ratio), the positive predictive value was 58%. Conversely, spirometry
      had a very favorable negative predictive value; only 2.4% of patients (32 of
      1,361) with a normal vital capacity (VC) on spirometry had a restrictive defect
      by TLC measurement. The probability of a restrictive defect was directly and
      linearly related to the degree of reduction of FVC when the FVC was < 80% of
      predicted (p = 6.002). Combining the FVC and the FEV1/FVC ratio improved the
      predictive ability of spirometry; for all values of FVC < 80% of the predicted
      amount, the likelihood of restrictive disease increased as the FEV1/FVC ratio
      increased. CONCLUSIONS: Spirometry is very useful at excluding a restrictive
      defect. When the VC is within the normal range, the probability of a restrictive
      defect is < 3%, and unless restrictive lung disease is suspected a priori,
      measurement of lung volumes can be avoided. However, spirometry is not able to
      accurately predict lung restriction; < 60% of patients with a classical
      spirometric restrictive pattern had pulmonary restriction confirmed on lung
      volume measurements. For these patients, measurement of the TLC is needed to
      confirm a true restrictive defect.

PMID- 10084507
TI  - Anterior limited thoracotomy with intrathoracic illumination for lung cancer: its
      advantages over anteroaxillary and posterolateral thoracotomy.
AB  - STUDY OBJECTIVE: We developed anterior limited thoracotomy (ALT) with
      intrathoracic illumination for curative resection of lung cancer. The present
      study evaluated the benefits of ALT by retrospective comparison with
      anteroaxillary thoracotomy (AAT) and posterolateral thoracotomy (PLT). DESIGN:
      Lung cancer patients, who underwent lobectomy via ALT (n = 28), AAT (n = 28), and
      PLT (n = 28), were matched by gender and age. Operating time, blood loss during
      operation, chest tube drainage volume 24 h after surgery, chest tube drainage
      duration, and vital capacity (VC) and chest pain from early to late postoperative
      period were studied for ALT, AAT, and PLT. Early postoperative chest pain was
      evaluated by a visual analog scale and analgesic requirements, and chronic pain
      was divided into five grades. RESULTS: No difference was observed in operating
      time among ALT, AAT, and PLT. ALT has the following advantages over PLT: (1) less
      blood loss during surgery (p < 0.05); (2) reduced postoperative drainage volume
      (p < 0.05) resulting in shorter chest tube drainage (p < 0.001); (3) diminished
      impairment of VC for 1 week to 6 months after surgery (p < 0.01 or p < 0.001);
      and (4) reduced pain from 1 day and 6 months after surgery (p < 0.001). ALT also
      has the advantage over AAT in reduced pain 5 days (p < 0.01) and 7 days (p <
      0.05) after surgery and in decreased analgesic requirements during 14 days after
      surgery (p < 0.05). CONCLUSION: ALT is a sufficient and minimally invasive
      thoracotomy alternative to PLT or AAT for curative lung cancer resection.

PMID- 10084508
TI  - A 16-year-old with left-sided pneumothorax.

PMID- 10084509
TI  - A 60-year-old man with septic arthritis and hypotension after a fall.

PMID- 10084510
TI  - Polymyalgia, hypersensitivity pneumonitis and other reactions in patients
      receiving HMG-CoA reductase inhibitors: a report of ten cases.
AB  - Ten patients who take hydroxy-methylglutaryl coenzyme A reductase inhibitors, or
      statin medications, and experience adverse reactions are described. All patients
      experienced various manifestations of hypersensitivity while receiving the drugs.
      One patient is described with hypersensitivity pneumonitis, which was graphically
      demonstrated by both high resolution computerized axial tomography and open lung
      biopsy.

PMID- 10084511
TI  - Pulmonary malacoplakia associated with Rhodococcus equi infection in a patient
      with AIDS.
AB  - An AIDS patient with a cavitary lung lesion was found to have pulmonary
      malacoplakia associated with Rhodococcus equi infection. The diagnosis was based
      on the typical histologic features of transbronchial biopsy and a positive
      bacterial culture. All 13 reported cases of AIDS patients with pulmonary
      malacoplakia were associated with R equi. The recognition of this unique entity
      is important because of its responsiveness to therapy.

PMID- 10084512
TI  - Microvascular pulmonary emboli secondary to precipitated crystals in a patient
      receiving total parenteral nutrition: a case report and description of the high
      resolution CT findings.
AB  - A patient with a history of a small-bowel transplant that was subsequently
      resected required total parenteral nutrition for nutritional supplementation.
      While receiving therapy, he developed chest tightness, shortness of breath, and
      fever. The chest radiograph showed bilateral reticulonodular opacities, and the
      high-resolution CT scan demonstrated diffuse, poorly marginated micronodular
      opacities in a miliary pattern. Pathology specimens obtained by transbronchial
      biopsy revealed amorphous material obstructing the pulmonary microvasculature.
      Microvascular emboli secondary to precipitated crystals is a potential
      complication of total parenteral nutrition. An awareness of the factors that
      influence crystal solubility may prevent adverse interactions in patients who
      require parenteral nutrition.

PMID- 10084513
TI  - Thrombolysis with resolution of pulmonary hypertension in a heart transplant
      candidate.
AB  - We report a patient with idiopathic cardiomyopathy and high pulmonary resistance
      due to pulmonary emboli of unknown age. Successful thrombolytic therapy returned
      his pulmonary resistance to normal, allowing orthotopic cardiac transplantation.
      This case underscores the need to aggressively diagnose and treat pulmonary
      emboli in potential transplant candidates.

PMID- 10084514
TI  - Endobronchial stenting for extrinsic compression caused by pulsatile pulmonary
      artery in a 4-week-old infant.
AB  - Respiratory compromise secondary to external vascular compression may complicate
      the course of infants and neonates undergoing repair of congeni tal heart
      disease. Management of such complications usually involves prolonged ventilatory
      support and even additional high-risk surgical procedures. In recent years,
      endobronchial placement of self-expanding stents became a realistic treatment
      option, although there is controversy as to which of the many stents available
      today give the best results. We report the first successful endobronchial
      placement of a self-expanding stent in a 4-week-old infant. This conservative
      treatment for extrinsic airway compression led to the rapid extubation and
      recovery of the patient.

PMID- 10084515
TI  - A reversible cause of hypercapnic respiratory failure: lower motor neuronopathy
      associated with renal cell carcinoma.
AB  - We describe a unique case of a patient with a reversible paraneoplastic motor
      neuronopathy who presented with hypercapnic respiratory failure. The patient
      developed progressive respiratory and limb muscle weakness until treated with
      removal of a renal cell carcinoma, which was followed by a complete resolution of
      neuromuscular symptoms. The literature of paraneoplastic motor neuronopathies is
      reviewed, specifically in reference to respiratory failure.

PMID- 10084516
TI  - Coronavirus pneumonia following autologous bone marrow transplantation for breast
      cancer.
AB  - Infectious bronchitis virus, otherwise known as coronavirus, can cause mild upper
      respiratory tract illnesses in children and adults. Rarely has coronavirus been
      linked, either by serology or nasal wash, to pneumonia. We report a case of a
      young woman who, following treatment for stage IIIA breast cancer using a high
      dose chemotherapy regimen followed by autologous bone marrow and stem cell
      transplantation, developed respiratory failure and was found to have coronavirus
      pneumonia as diagnosed by electron microscopy from BAL fluid. We propose that
      coronavirus should be considered in the differential diagnosis of acute
      respiratory failure in cancer patients who have undergone high-dose chemotherapy
      and autologous hematopoietic support.

PMID- 10084517
TI  - Chagas' disease.

PMID- 10084518
TI  - Possible diaphragmatic ischemia following harvesting of the internal mammary
      artery.

PMID- 10084519
TI  - Giant schwannoma of the posterior mediastinum.

PMID- 10084520
TI  - Squamous cell carcinoma with unknown origin: metastasis to mediastinal lymph
      nodes.

PMID- 10084521
TI  - A critical appraisal of the chronic whiplash syndrome.

PMID- 10084522
TI  - Infections and the Guillain-Barre syndrome.

PMID- 10084523
TI  - Orthostatic tremor.

PMID- 10084524
TI  - Pain after whiplash: a prospective controlled inception cohort study.
AB  - OBJECTIVES: In Lithuania, there is little awareness of the notion that chronic
      symptoms may result from rear end collisions via the so-called whiplash injury.
      After most such collisions no contact with the health service is established. An
      opportunity therefore exists to study post-traumatic pain without the confounding
      factors present in western societies. METHODS: In a prospective, controlled
      inception cohort study, 210 victims of a rear end collision were consecutively
      identified from the daily records of the Kaunas traffic police. Neck pain and
      headache were evaluated by mailed questionnaires shortly after the accident,
      after 2 months, and after 1 year. As controls, 210 sex and age matched subjects
      were randomly taken from the population register of the same geographical area
      and evaluated for the same symptoms immediately after their identification and
      after 1 year. RESULTS: Initial pain was reported by 47% of accident victims; 10%
      had neck pain alone, 18% had neck pain together with headache, and 19% had
      headache alone. The median duration of the initial neck pain was 3 days and
      maximal duration 17 days. The median duration of headache was 4.5 hours and the
      maximum duration was 20 days. After 1 year, there were no significant differences
      between the accident victims and the control group concerning frequency and
      intensity of these symptoms. CONCLUSIONS: In a country were there is no
      preconceived notion of chronic pain arising from rear end collisions, and thus no
      fear of long term disability, and usually no involvement of the therapeutic
      community, insurance companies, or litigation, symptoms after an acute whiplash
      injury are self limiting, brief, and do not seem to evolve to the so-called late
      whiplash syndrome.

PMID- 10084525
TI  - Evidence for a non-orthostatic origin of orthostatic tremor.
AB  - OBJECTIVES: Orthostatic tremor was first described by Heilman in 1984. It usually
      occurs in the legs during stance and decreases markedly during sitting or
      walking. The aim of this study was to determine if orthostatic tremor is
      invariably associated with the orthostatic and weight bearing conditions in the
      arms and legs, and to investigate the features of orthostatic tremor under
      different levels of peripheral loading. METHODS: Multichannel surface EMG
      recordings were obtained under different conditions (body posture and peripheral
      loading) from the proximal arm and leg muscles of seven patients fulfilling the
      clinical and electrophysiological criteria of orthostatic tremor. RESULTS: In
      weight bearing positions (stance; weight bearing on the hands on all fours), all
      patients showed 13 Hz-16 Hz tremor activity, predominantly in the active limb. No
      tremor activity could be found in a supine position with muscles at rest.
      Isometric contraction of the limbs in the supine position led to synchronous 13
      Hz-16 Hz rhythmic activity in five patients. No tremor was seen when the subjects
      were suspended in a harness with relaxed legs. Isometric contraction of the legs
      in this position produced tremor in two patients. A stepwise reduction of the
      body weight by a harness reduced the tremor activity. Additional loading (10 kg
      20 kg) during stance led to an increase in tremor amplitude, but tremor frequency
      remained unchanged. CONCLUSIONS: Orthostatic tremor is invariably present during
      stance or other weight bearing positions. It is not, however, always associated
      with orthostasis. In at least some patients it can be classified as an
      orthostasis independent action tremor. The failure of peripheral loading to
      modify tremor frequency indicates that orthostatic tremor may have a central,
      rather than a peripheral, origin.

PMID- 10084526
TI  - Multicentre European study of thalamic stimulation in parkinsonian and essential
      tremor.
AB  - OBJECTIVES: Thalamic stimulation has been proposed to treat disabling tremor. The
      aims of this multicentre study were to evaluate the efficacy and the morbidity of
      thalamic stimulation in a large number of patients with parkinsonian or essential
      tremor. METHODS: One hundred and eleven patients were included in the study and
      110 were implanted either unilaterally or bilaterally. Patients were evaluated
      with clinical scales, before and up to 12 months after surgery. RESULTS: Upper
      and lower limb tremor scores were reduced in both groups. Eighty five per cent of
      the electrodes satisfied the arbitrary criteria of two point reduction in rest
      tremor reduction in the parkinsonian tremor group and 89% for postural tremor
      reduction in the essential tremor group. In the parkinsonian tremor group, limb
      akinesia and limb rigidity scores were moderately but significantly reduced.
      Axial scores were unchanged. In the essential tremor group, head tremor was
      significantly reduced only at 3 months and voice tremor was non-significantly
      reduced. Activities of daily living were improved in both groups. Changes in
      medication were moderate. Adverse effects related to the surgery were mild and
      reversible. CONCLUSIONS: Thalamic stimulation was shown to be an effective and
      relatively safe treatment for disabling tremor. This procedure initially applied
      in a very limited number of centres has been successfully used in 13
      participating centres.

PMID- 10084527
TI  - Cognitive outcome after unilateral pallidal stimulation in Parkinson's disease.
AB  - OBJECTIVES: Chronic high frequency electrostimulation of the globus pallidus
      internus mimics pallidotomy and improves clinical symptoms in Parkinson's
      disease. The aim of this study was to investigate the cognitive consequences of
      unilateral deep brain stimulation. METHODS: Twenty non-demented patients with
      Parkinson's disease (age range 38-70 years) were neuropsychologically assessed 2
      months before and 3 months after unilateral pallidal stimulation. The cognitive
      assessment included measures of memory, spatial behaviour, and executive and
      psychomotor function. In addition to group analysis of cognitive change, a
      cognitive impairment index (CII) was calculated for each individual patient
      representing the percentage of cognitive measures that fell more than 1 SD below
      the mean of a corresponding normative sample. RESULTS: Neurological assessment
      with the Hoehn and Yahr scale and the unified Parkinson's disease rating scale
      disclosed a significant postoperative reduction in average clinical Parkinson's
      disease symptomatology (p<0.001). Repeated measures multivariate analysis of
      variance (using right/left side of stimulation as a between subjects factor)
      showed no significant postoperative change in cognitive performance for the total
      patient group (main effect of operation). The side of stimulation did not show a
      significant differential effect on cognitive performance (main effect of
      lateralisation). There was no significant operation by lateralisation interaction
      effect. Although the patients experienced significant motor symptom relief after
      pallidal stimulation, they remained mildly depressed after surgery. Analysis of
      the individual CII changes showed a postoperative cognitive decline in 30% of the
      patients. These patients were significantly older and took higher preoperative
      doses of levodopa than patients showing no change or a postoperative cognitive
      improvement. CONCLUSIONS: Left or right pallidal stimulation for the relief of
      motor symptoms in Parkinson's disease seems relatively safe, although older
      patients and patients needing high preoperative doses of levodopa seem to be more
      vulnerable for cognitive decline after deep brain stimulation.

PMID- 10084528
TI  - Saccadic performance characteristics and the behavioural neurology of Tourette's
      syndrome.
AB  - OBJECTIVE: To better understand the neuropathological correlates of Tourette's
      syndrome (TS), measures of saccadic eye movement performance were examined among
      patients with TS. METHODS: A case-control design was used. Twenty one patients
      with DSM-IV TS (mean age 40.6 years (SD 11.0); 38% female) mainly recruited from
      UCSD Psychiatry Services, and a community based sample of 21 normal subjects
      (mean age 34.6 years (SD 13.4); 43% women) participated in this study.
      Participants were administered ocular motor tasks assessing visual fixation, and
      the generation of prosaccades, predictive saccades, and antisaccades. Saccadic
      reaction time, amplitude, duration, and mean and peak velocity were computed.
      Intrusive saccades during visual fixation and the proportion of correct
      antisaccade responses were also evaluated. RESULTS: The groups had similar visual
      fixation performance. Whereas patients with TS generated prosaccades with normal
      reaction times and amplitudes, their saccade durations were shorter and their
      mean velocities were higher than in normal subjects. During a prosaccade gap
      task, patients with TS exhibited an increased proportion of anticipatory saccades
      (RTs<90). The proportion of "express" saccades (90<RTs<135) did not differ
      between groups. Patients with TS had fewer correct antisaccade responses than did
      normal subjects, an effect accounted for by 19% of the patients. Antisaccade
      reaction times among patients with TS were increased during an overlap version of
      the task. CONCLUSION: These findings suggest that TS mildly affects the ocular
      motor control circuitry associated with saccade inhibition.

PMID- 10084529
TI  - Subjective perception of body sway.
AB  - OBJECTIVES AND METHOD: The relation between body sway recorded through a
      stabilometric platform and the subjective report of steadiness was studied in 20
      young and 20 elderly subjects and 20 neuropathic and 20 parkinsonian patients
      standing upright. The trials were performed under two stances (feet apart, feet
      together) and two visual conditions (eyes open, eyes closed). At the end of each
      trial, subjects scored their performance on a scale from 10 (complete steadiness)
      to 0 (fall). RESULTS: In all subjects, independently of the stance conditions,
      the larger the body sway the smaller the reported score. The function best
      fitting this relation was linear when sway was expressed on a logarithmic scale.
      The scoring reproducibility proved high both within and across subjects. Despite
      the different body sways and scores recorded under the different visual and
      postural conditions (eyes closed>eyes open, feet together>feet apart) in all
      groups of subjects and patients, the slopes of the relations between sway and
      score were broadly superimposable. In the normal subjects, the scores were
      slightly higher during eyes open than eyes closed trials for corresponding body
      sways. This was interpreted as a sign of perception of greater stability when
      vision was allowed. Parkinsonian patients swayed to a similar extent as normal
      subjects, and their scores were accordingly similar, both with eyes open and eyes
      closed. Neuropathic patients swayed to a larger extent than normal subjects, and
      their scores were matched appropriately. Although the slope of their relation
      with eyes closed was not different from that of normal subjects, with eyes open
      it was steeper and similar to that with eyes closed, suggesting that these
      patients did not feel more stable when they could take advantage of vision.
      CONCLUSIONS: The subjective evaluation of body sway, irrespective of stance
      condition, age, neuropathy, and basal ganglia disease, reflects the actual sway,
      and is inversely proportional to the logarithm of the sway value. The remarkable
      similarity of the relation between score and sway across the various groups of
      subjects with eyes closed indicates a common mode of sway evaluation, possibly
      based on integration of several sensory inputs. All groups except neuropathic
      patients seem to take advantage of the redundancy of the inputs. Basal ganglia
      integrity does not seem to have a role in the evaluation of sway.

PMID- 10084531
TI  - Theodor Meynert (1833-92).

PMID- 10084530
TI  - Three dimensional MRI estimates of brain and spinal cord atrophy in multiple
      sclerosis.
AB  - OBJECTIVE: The association between brain atrophy and permanent functional
      deficits in multiple sclerosis and the temporal relation between atrophy and the
      clinical disease course have seldom been investigated. This study aims to
      determine the amount of infratentorial and supratentorial atrophy in patients by
      comparison with healthy controls, to establish the relation between atrophy and
      disability, and to derive the rates of volume loss in individual patients from
      their estimated disease durations. METHODS: Three dimensional acquired MRI was
      performed on 20 relapsing-remitting and 20 secondary progressive multiple
      sclerosis patients and 10 control subjects. Volume data on infratentorial and
      supratentorial structures were obtained using the Cavalieri method of modern
      design stereology in combination with point counting. Corpus callosal sectional
      area and "T2 lesion load" were also determined. RESULTS: Significantly reduced
      infratentorial and cerebral white matter volumes and corpus callosal sectional
      areas occurred in all patients compared with controls (p=0.0001-0.004). Mean
      estimates of volume loss in the cohort were -21%, -19%, -46%, and -12% for the
      brain stem, cerebellum, upper cervical cord and white matter, respectively, and 
      21% for the corpus callosal sectional area. Analysis of the amount of atrophy
      (volume differences between patients and controls) showed that upper cervical
      cord and cerebral white matter atrophy correlated with the expanded disability
      status scale (r=-0.37 and -0.37, p=0.018-0.023) and the Scripps neurologic rating
      scale scores (r=+0.49 and +0.43, p=0.002-0.007). There was no relation between
      estimated volume loss in the supratentorial and infratentorial compartments. The
      "T2 lesion load" was associated with ventricular enlargement and corpus callosal
      atrophy (r=+0.50 and -0.55, p=0.0003-0.0012). Infratentorial atrophy rates
      correlated with baseline exacerbation rates (r=-0.50 to -0.48, p=0.0016-0.0021)
      and were higher in relapsing-remitting than secondary progressive patients
      (p=0.009-0.02). CONCLUSIONS: Significant cerebral and spinal cord volume
      reductions occurred in both patient subgroups compared with controls. Functional
      correlates were found with estimated volume loss in the upper cervical cord and
      cerebral white matter. Particularly for infratentorial structures, estimated
      rates of atrophy were higher in relapsing-remitting than secondary progressive
      patients, suggesting that atrophy, perhaps mainly due to tract degeneration,
      begins early in multiple sclerosis and may relate predominantly to acute
      inflammatory events, with or without other gradual non-inflammatory processes
      later in the disease course.

PMID- 10084532
TI  - Comparative study of 99mTc-ECD and 99mTc-HMPAO for peri-ictal SPECT: qualitative
      and quantitative analysis.
AB  - OBJECTIVES: Most studies that clinically validated peri-ictal SPECT in
      intractable partial epilepsy had used technetium-99m-hexamethylpropylene amine
      oxime (99mTc-HMPAO or 99mTc-exametazime) as the radiopharmaceutical. Because of
      some theoretical advantages, technetium-99m-ethyl cysteinate diethylester (99mTc
      ECD or 99mTc-bicisate) is increasingly being used instead. This study compares
      unstabilised 99Tc-HMPAO and 99mTc-ECD in the performance of peri-ictal SPECT in
      partial epilepsy. METHODS: The injection timing and localisation rates in 49
      consecutive patients with partial epilepsy who had peri-ictal injections with
      unstabilised 99mTc-HMPAO were compared with 49 consecutive patients who had peri
      ictal injections with 99mTc-ECD. Quantitative cortical/subcortical and
      cortical/extracerebral uptake ratios were also compared. Subtraction SPECT
      coregistered to MRI (SISCOM) was performed in patients whose interictal SPECTS
      were available. RESULTS: In the 99mTc-ECD patients, the latency from seizure
      commencement to injection was shorter (median 34 v 80 seconds, p<0.0001) and
      there was a lower rate of postictal injections (16.3% v 57.1%, p<0.0001). The
      cortical/extracerebral and cortical/subcortical uptake ratios were greater in the
      99mTc-ECD images (median 5.0 v 3.6, and 2.5 v 2.2 respectively; both p<0.005),
      but the relative peri-ictal increase in uptake in the cortical focus did not
      differ significantly (median 37.0% v 37.0%; p>0.05). Blinded review of the SISCOM
      images were localising in a higher proportion of the 99mTc-ECD patients (40/45
      (88.9%) v 25/37 (67.6%), p<0.05), and had a better concordance with EEG, MRI, and
      with the discharge diagnosis. CONCLUSION: 99mTc-ECD compares favourably with
      unstabilised 99mTc-HMPAO as a radiopharmaceutical for peri-ictal SPECT studies.
      Its use results in earlier injections and less frequent postictal injections than
      unstabilised 99mTc-HMPAO, thereby enhancing the sensitivity and the specificity
      of peri-ictal SPECT for the localisation of intractable partial epilepsy.

PMID- 10084533
TI  - Pontine lesions mimicking acute peripheral vestibulopathy.
AB  - OBJECTIVES: Clinical signs of acute peripheral vestibulopathy (APV) were
      repeatedly reported with pontine lesions. The clinical relevance of such a
      mechanism is not known, as most studies were biased by patients with additional
      clinical signs ofbrainstem dysfunction. METHODS: Masseter reflex (MassR), blink
      reflex (BlinkR), brainstem auditory evoked potentials (BAEPs), and DC electro
      oculography (EOG) were tested in 232 consecutive patients with clinical signs of
      unilateral APV. RESULTS: Forty five of the 232 patients (19.4%) had at least one
      electrophysiological abnormality suggesting pontine dysfunction mainly due to
      possible vertebrobasilar ischaemia (22 patients) and multiple sclerosis (eight
      patients). MassR abnormalities were seen in 24 patients, and EOG abnormalities of
      saccades and following eye movements occurred in 22 patients. Three patients had
      BlinkR-R1 abnormalities, and one had delayed BAEP waves IV and V. Clinical
      improvement was almost always (32 of 34 re-examined patients) associated with
      improvement or normalisation of at least one electrophysiological abnormality.
      Brain MRI was done in 25 of the 44 patients and confirmed pontine lesions in six
      (two infarcts, three inflammations, one tumour). CONCLUSIONS: Pontine dysfunction
      was suggested in 45 of 232 consecutive patients with clinical signs of APV on the
      basis of abnormal electrophysiological findings, and was mainly attributed to
      brainstem ischaemia and multiple sclerosis. The frequency of pontine lesions
      mimicking APV is underestimated if based on MRI established lesions only.

PMID- 10084534
TI  - Prognostic factors in presurgical assessment of frontal lobe epilepsy.
AB  - OBJECTIVES: To determine predictors for surgical outcome in the presurgical
      assessment of frontal lobe epilepsy. METHODS: Thirty seven patients were operated
      on for frontal lobe epilepsy between 1975 and 1996. Their medical records were
      reviewed for ictal semiology, age at onset, duration of the epilepsy, age at
      operation, preoperative interictal and ictal encephalographic findings, and
      abnormalities on neuroimaging and neuropsychological testing. In addition, type
      of resection and pathology were compared with surgical outcome. RESULTS:
      Univariate statistical analysis showed that the presence of a focal abnormality
      on neuroimaging was associated with favourable outcome. The presence of the
      following ictal findings was associated with poor outcome: autonomic
      manifestations, eye deviation, head version contralateral to the operated side,
      and bilateral or multifocal ictal onset. Fifteen patients had secondarily
      generalised interictal discharges and, interestingly, their presence was not
      associated with poor outcome. Multivariate logistic regression showed that the
      presence of a focal abnormality on neuroimaging was significantly associated with
      a favourable outcome while contralateral head version was the only variable
      significantly associated with poor surgical outcome. CONCLUSIONS: A focal
      abnormality on neuroimaging was the only variable which was significantly
      associated with a favourable surgical outcome, whereas contralateral head version
      was the most significant predictor for a poor outcome. The presence of
      generalised discharges before surgery was not associated with poor outcome.

PMID- 10084535
TI  - Basilar impression complicating osteogenesis imperfecta type IV: the clinical and
      neuroradiological findings in four cases.
AB  - OBJECTIVES: To describe the clinical and neuroradiological features of basilar
      impression in patients with osteogenesis imperfecta type IV. METHODS: Four
      patients with basilar impression were ascertained in a population study of
      osteogenesis imperfecta. All four had detailed clinical and neuroradiological
      examination with both CT and MRI of the craniocervical junction and posterior
      fossa structures. RESULTS: All four showed significant compression of the
      posterior fossa structures and surgical decompression was performed with relief
      of symptoms. CONCLUSION: Symptoms of cough headache and trigeminal neuralgia
      occurring in patients with osteogenesis imperfecta are indications for detailed
      clinical and neuroradiological investigation to document basilar impression.

PMID- 10084536
TI  - Global aphasia without hemiparesis: language profiles and lesion distribution.
AB  - OBJECTIVES: Global aphasia without hemiparesis (GAWH) is an uncommon stroke
      syndrome involving receptive and expressive language impairment, without the
      hemiparesis typically manifested by patients with global aphasia after large left
      perisylvian lesions. A few cases of GAWH have been reported with conflicting
      conclusions regarding pathogenesis, lesion localisation, and recovery. The
      current study was conducted to attempt to clarify these issues. METHODS: Ten
      cases of GAWH were prospectively studied with language profiles and lesion
      analysis; five patients had multiple lesions, four patients had a single lesion,
      and one had a subarachnoid haemorrhage. Eight patients met criteria for
      cardioembolic ischaemic stroke. RESULTS: Cluster analysis based on acute language
      profiles disclosed three subtypes of patients with GAWH; these clusters persisted
      on follow up language assessment. Each cluster evolved into a different aphasia
      subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia
      (TCM). Composite lesion analysis showed that persistent GAWH was related to
      lesioning of the left superior temporal gyrus. Patients with acute GAWH who
      evolved into TCM type aphasia had common lesioning of the left inferior frontal
      gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved
      into Wernicke's type aphasia were characterised by lesioning of the left
      precentral and postcentral gyri. Recovery of language was poor in all but one
      patient. CONCLUSIONS: Although patients with acute GAWH are similar on
      neurological examination, they are heterogeneous with respect to early aphasia
      profile, language recovery, and lesion profile.

PMID- 10084537
TI  - Early diagnosis of subependymal giant cell astrocytoma in children with tuberous
      sclerosis.
AB  - OBJECTIVES: Intraventricular astrocytomas (subependymal giant cell astrocytomas)
      of tuberous sclerosis have a poor prognosis due to the obstruction of CSF flow.
      The aim of this study was to determine whether they could be differentiated
      during childhood and at an early preclinical stage, from subependymal nodules
      without any growing potential. METHODS: The first two MRIs of all children
      referred to this neuropaediatric centre between 1987 and 1996 were
      retrospectively blindly reviewed. RESULTS: Out of 60 patients, 24 disclosed
      subependymal nodules localised near the foramen of Monro, and eight of the 24
      developed astrocytomas. Subependymal nodules were first detectable on MRI from 1
      year of age in all cases and the first MRI evidence of growth occurred between 1
      and 9 years (mean 4 years). At an early stage, subependymal nodules had different
      characteristics in patients who developed subependymal giant cell astrocytomas
      from those who did not. The nodules over 5 mm in diameter that were incompletely
      calcified and enhanced by gadolinium were at higher risk of growing, particularly
      in children with a familial history of tuberous sclerosis. To detect the
      subependymal giant cell astrocytomas earlier in tuberous sclerosis, it is
      advisible to systematically perform an MRI examination before 2 years of age and
      to repeat it every year if the patient has risk factors for developing
      astrocytomas.

PMID- 10084538
TI  - Antiganglioside antibodies in Guillain-Barre syndrome after a recent
      cytomegalovirus infection.
AB  - OBJECTIVE: To study the association between anti-ganglioside antibody responses
      and Guillan-Barre syndrome (GBS) after a recent cytomegalovirus (CMV) infection.
      METHODS: Enzyme linked immunosorbant assay (ELISA) was undertaken on serum
      samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection
      (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases
      (OND), 11 patients with a recent CMV infection but without neurological
      involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but
      without neurological involvement, and 20 normal control (NC) subjects. RESULTS:
      IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14
      patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum
      samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients.
      IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11
      OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and
      to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection
      had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a
      (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none
      being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples
      remained positive at this dilution. CONCLUSION: Antibodies to ganglioside GM2 are
      often associated with GBS after CMV infection, but their relevance is not known.
      It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely
      responsible and an additional factor is required to elicit GBS.

PMID- 10084539
TI  - Parkinson's syndrome after closed head injury: a single case report.
AB  - A 36 year old man, who sustained a skull fracture in 1984, was unconscious for 24
      hours, and developed signs of Parkinson's syndrome 6 weeks after the injury. When
      assessed in 1995, neuroimaging disclosed a cerebral infarction due to trauma
      involving the left caudate and lenticular nucleus. Parkinson's syndrome was
      predominantly right sided, slowly progressive, and unresponsive to levodopa
      therapy. Reaction time tests showed slowness of movement initiation and execution
      with both hands, particularly the right. Recording of movement related cortical
      potentials suggested bilateral deficits in movement preparation.
      Neuropsychological assessment disclosed no evidence of major deficits on tests
      assessing executive function or working memory, with the exception of selective
      impairments on the Stroop and on a test of self ordered random number sequences.
      There was evidence of abulia. The results are discussed in relation to previous
      literature on basal ganglia lesions and the effects of damage to different points
      of the frontostriatal circuits.

PMID- 10084540
TI  - Novel mutation of the P0 extracellular domain causes a Dejerine-Sottas syndrome.
AB  - A patient is described with a Dejerine-Sottas syndrome caused by a novel
      heterozygous Cys(98)Tyr mutation in the extracellular domain of the major
      peripheral myelin protein zero (P0ex). Homotypical interactions between P0ex
      tetramers of apposed extracellular faces of the Schwann cell membrane play a
      crucial part in myelin compaction. The amino acid change disrupts a unique
      disulphide bond that stabilises the immunoglobulin-like structure of P0ex and it
      is predicted to cause severe dehypomyelination through dominant negative effects
      on the wild type protein.

PMID- 10084541
TI  - Decreased CGRP, but preserved Trk A immunoreactivity in nerve fibres in inflamed
      human superficial temporal arteries.
AB  - The peptidergic sensory innervation of cranial blood vessels may play an
      important part in vascular head pain. The neuropeptides calcitonin gene-related
      peptide (CGRP) and substance P in sensory fibres are dependent on nerve growth
      factor (NGF) produced by the blood vessels, and when released from nerve
      terminals mediate neurogenic inflammation. NGF is increased in inflamed tissues,
      and acts via its high affinity receptor trk A on nociceptor fibres to produce
      hyperalgesia. CGRP and trk A immunoreactive nerve fibres have therefore been
      studied, for the first time, in inflamed (n=7) and non-inflamed (n=10) temporal
      arteries biopsied from patients with headache and suspected giant cell arteritis.
      CGRP immunoreactivity was markedly decreased to absent in adventitial nerve
      fibres in inflamed regions of vessels, which may reflect secretion from nerve
      terminals, as CGRP immunoreactivity could still be seen in nerve trunks in
      periadventitial tissue. Trk A immunoreactive nerve fibres were found in a similar
      distribution to CGRP containing nerve fibres in non-inflamed vessels, and the trk
      A immunoreactivity was virtually unchanged in inflamed vessels. The evidence
      supports a role for NGF related mechanisms in inflammatory vascular head pain.
      Anti-NGF or anti-trk A agents may represent novel analgesics in this condition.

PMID- 10084542
TI  - Conduction aphasia elicited by stimulation of the left posterior superior
      temporal gyrus.
AB  - OBJECTIVE: Disruption of fascicular tracts that connect Wernicke's to Broca's
      areas is the classic mechanism of conduction aphasia. Later work has emphasised
      cortical mechanisms. METHODS: To determine the distribution of language on
      dominant cortex, electrical cortical stimulation was performed using implanted
      subdural electrodes during brain mapping before epilepsy surgery. RESULTS: A
      transient, isolated deficit in repetition was elicited with stimulation of the
      posterior portion of the dominant superior temporal gyrus. CONCLUSION: This
      finding suggests that cortical dysfunction, not just white matter disruption, can
      induce conduction aphasia.

PMID- 10084543
TI  - Cluster headache-like attack as an opening symptom of a unilateral infarction of
      the cervical cord: persistent anaesthesia and dysaesthesia to cold stimuli.
AB  - A 54 year old man experienced excruciating left retro-orbital pain with
      lacrimation and redness of the eye representative of a cluster headache attack.
      This was followed by left hemiparesis with plegia of the lower limb and left
      Horner's syndrome. Five days later the hemiparesis recovered while the patient
      developed hypoanaesthesia to cold stimuli that evoked painful burning
      dysaesthesia on the right side below the C4 level. MRI disclosed a discrete
      infarct in the left lateral aspect of the cord at C2 level concomitant to a left
      vertebral artery thrombosis. This limited infarct and the clinical symptoms
      suggest a hypoperfusion in the peripheral arterial system of the left hemicord,
      supplied both by the anterior and posterior spinal arteries. Cluster headache
      like attack and persistent dysaesthesia to cold stimuli are discussed
      respectively in view of the central sympathetic involvement and partial
      spinothalamic system dysfunction.

PMID- 10084544
TI  - EEG findings in dementia with Lewy bodies and Alzheimer's disease.
AB  - OBJECTIVES: To evaluate the role of the EEG in the diagnosis of dementia with
      Lewy bodies (DLB). METHODS: Standard EEG recordings from 14 patients with DLB
      confirmed at postmortem were examined and were compared with the records from 11
      patients with Alzheimer's disease confirmed at postmortem RESULTS: Seventeen of
      the total of 19 records from the patients with DLB were abnormal. Thirteen showed
      loss of alpha activity as the dominant rhythm and half had slow wave transient
      activity in the temporal lobe areas. This slow wave transient activity correlated
      with a clinical history of loss of consciousness. The patients with Alzheimer's
      disease were less likely to show transient slow waves and tended to have less
      marked slowing of dominant rhythm. CONCLUSIONS: The greater slowing of the EEG in
      DLB than in Alzheimer's disease may be related to a greater loss of choline
      acetyltransferase found in DLB. Temporal slow wave transients may be a useful
      diagnostic feature in DLB and may help to explain the transient disturbance of
      consciousness which is characteristic of the disorder.

PMID- 10084545
TI  - Cerebral mucormycosis.

PMID- 10084546
TI  - Abdominal pseudohernia caused by diabetic truncal radiculoneuropathy.

PMID- 10084547
TI  - Creutzfeldt-Jakob disease presenting as complex partial status epilepticus: a
      report of two cases.

PMID- 10084548
TI  - Childhood demyelinating diseases with a prolonged remitting course and their
      relation to Schilder's disease: report of two cases.

PMID- 10084549
TI  - Guillain-Barre syndrome after heat stroke.

PMID- 10084550
TI  - Hydrodynamic performance of a new siphon preventing device: the SiphonGuard.

PMID- 10084551
TI  - Convulsions induced by donepezil.

PMID- 10084552
TI  - Severe toxic neuropathy due to fibrates.

PMID- 10084553
TI  - Macs with multiple sclerosis.

PMID- 10084554
TI  - High incidence and prevalence of multiple sclerosis in south east Scotland:
      evidence of a genetic predisposition.

PMID- 10084555
TI  - Albendazole therapy for subarachnoid cysticerci: clinical and neuroimaging
      analysis of 17 patients.

PMID- 10084556
TI  - Clinical review 101: Thyrotropin may not be the dominant growth factor in benign
      and malignant thyroid tumors.

PMID- 10084557
TI  - Shortcomings in the low-dose (1 microg) ACTH test for the diagnosis of ACTH
      deficiency states.

PMID- 10084558
TI  - Comparison of the low dose short synacthen test (1 microg), the conventional dose
      short synacthen test (250 microg), and the insulin tolerance test for assessment
      of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease.
AB  - There is still uncertainty about what is the most appropriate test for assessment
      of the integrity of the hypothalamo-pituitary-adrenal (HPA) axis. Many advocate
      the insulin tolerance test (ITT), but this is unpleasant and resource intensive,
      and may occasionally give misleading results. The conventional [250 microg
      tetracosactrin, ACTH-(1-24)] short synacthen test (SST) has been used as a simple
      alternative to the ITT, but it has produced some falsely reassuring results with
      potentially serious consequences. A low dose [1 microg tetracosactrin, ACTH-(1
      24)] short synacthen test (LDSST) has recently been advocated as a more reliable
      and safer alternative to ITT. Some studies, however, have failed to demonstrate
      any difference between SST and LDSST. The purpose of this study was to assess the
      clinical usefulness of LDSST compared to SST and ITT in patients with pituitary
      disease. We studied 64 patients with suspected or proven pituitary disease. All
      patients underwent SST and LDSST. Forty-two patients underwent ITT. There was a
      high correlation between the ITT and LDSST peak cortisol responses (r = 0.89; P <
      0.0001), the ITT and SST 30 min cortisol levels (r = 0.83; P < 0.0001), and the
      LDSST peak cortisol response and the SST 30 min cortisol level (r = 0.85; P <
      0.0001). In the LDSST, all but six patients achieved maximal cortisol response by
      30 min. A plasma cortisol cut-off of 600 nmol/L is more helpful than 500 nmol/L
      for clinical decision-making using either the SST 30 min cortisol level or the
      LDSST peak cortisol response. The sensitivity of the LDSST was 100% (cortisol
      response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring
      results. SST (pass cortisol level, >600 nmol/L) was less sensitive than LDSST, it
      produced 2 of 64 (3%) falsely reassuring results. Even the ITT (pass cortisol
      level, >500 nmol/L) failed to identify one patient with clinically evident
      cortisol deficiency. The results of this study indicate that both SST and LDSST,
      at a cortisol cut-off of 600 nmol/L, are safe for the purpose of clinical
      decision-making with regard to steroid replacement therapy in patients with
      pituitary disease. As the LDSST produced no falsely reassuring decisions, we
      suggest that this could replace the SST and ITT for initial evaluation of the HPA
      axis in patients with pituitary disease. We suggest administering 1 microg
      tetracosactrin, i.v., with sampling at 0, 20, and 30 min.

PMID- 10084559
TI  - Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an
      adolescent girl with a novel AIRE mutation: response to immunosuppressive
      therapy.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare
      autosomal recessive disorder for which the gene (AIRE) has recently been
      identified on chromosome 21q22.3. We present the mutational analyses of a French
      Canadian family with APECED, in which there are two affected siblings, as well as
      the response to cyclosporine A(CyA) therapy in the index patient, the eldest
      sibling. Haplotype analysis suggested compound heterozygozity at the AIRE locus.
      Direct sequencing of exon 8 revealed a previously described mutation, a 13-bp
      deletion (1085-1097) of maternal origin, found in the index patient, her affected
      sister, and her unaffected sister. A novel missense mutation characterized by a T
      ->G transversion at nucleotide position 398, resulting in a leu-->arg amino acid
      substitution (L93R), was found in exon 2. The mutation was present in the father,
      the brother, the index patient, and the affected sister. The presence of the
      mutation in the propositus was verified by cloning of PCR products from genomic
      DNA. The mutation destroys a PstI restriction enzyme site, as confirmed in the
      aforementioned patients. Screening of 50 French-Canadian controls with PstI
      digestion did not show destruction of the restriction-enzyme site. The index
      patient's phenotype was severe, manifested by classic features of the illness
      (adrenal insufficiency, hypoparathyroidism, candidiasis, and keratoconjunctivitis
      with alopecia universalis), as well as by severe exocrine pancreatic
      insufficiency, diabetes mellitus, hepatic inflammation, growth hormone (GH)
      deficiency due to lymphocytic hypophysitis, and primary ovarian failure. Oral CyA
      (5 mg/kg/day) was initiated at 13 yr of age. After 8 months of therapy,
      stimulated pancreatic lipase increased 24-fold with normalization of stool fat
      (from 31.5 g/day to 2.5 g/day, normal(N) < 5). There was complete resolution of
      her photophobia, and considerable hair regrowth was diffusely apparent. Minimal
      side effects were noted. Our experience supports the use of oral CyA for the
      treatment of severe APECED-associated exocrine pancreatic failure and
      keratoconjunctivitis.

PMID- 10084560
TI  - Association of collagen type 1 alpha1 gene polymorphism with bone density in
      early childhood.
AB  - Osteoporosis is a disease characterized by the development of nontraumatic
      fractures, most commonly in the vertebrae of elderly women. Approximately 500,000
      elderly women in the United States are newly diagnosed with vertebral fractures
      every year, as the compressive strength of the vertebra, mainly determined by the
      density of cancellous bone and its cross-sectional area, declines with age. A
      recent study in women suggested that a polymorphism in the Sp1 binding site of
      the collagen type I gene (COLIA1) was related to decreased vertebral bone mass
      and vertebral fractures. Determining the phenotypic trait(s) responsible for this
      relationship and whether this association is manifested in childhood would
      further define the structural basis for decreased bone mass and help identify
      children "at risk" for fractures later in life. We therefore studied the COLIA1
      gene polymorphism and measurements of the size and the density of vertebral bone
      in 109 healthy, prepubertal girls. On average, 22 girls with the Ss genotype and
      one girl with the ss genotype had 6.7% and 49.4% lower cancellous bone density in
      the vertebrae than girls with the SS genotype. In contrast, there was no
      association between the size of the vertebrae and the COLIA1 genotypes.

PMID- 10084561
TI  - Genetic control of 24-hour growth hormone secretion in man: a twin study.
AB  - The aim of this study was to delineate the contributions of genetic and
      environmental factors in the regulation of the 24-h GH secretion. The 24-h
      profile of plasma GH was obtained at 15-min intervals in 10 pairs of monozygotic
      and 9 pairs of dizygotic normal male twins, aged 16-34 yr. Sleep was
      polygraphically monitored. Significant pulses of GH secretion were identified
      using a modification of the computer algorithm ULTRA. For each significant pulse,
      the amount of GH secreted was calculated by deconvolution. A procedure specially
      developed for twin studies was used to partition the variance of investigated
      parameters into genetic and environmental contributions. A major genetic effect
      was evidenced on GH secretion during wakefulness (with a heritability estimate of
      0.74) and, to a lesser extent, on the 24-h GH secretion. Significant genetic
      influences were also identified for slow wave sleep and height. These data
      demonstrate that human GH secretion in young adulthood is markedly dependent on
      genetic factors.

PMID- 10084562
TI  - Independent influence of age on basal insulin secretion in nondiabetic humans.
      European Group for the Study of Insulin Resistance.
AB  - Glucose tolerance deteriorates with aging. To test whether age per se impairs
      basal beta-cell function, we analyzed retrospective clamp data from a large group
      (n = 957) of nondiabetic Europeans over the 18-85 yr age range (the European
      Group for the Study of Insulin Resistance database). In this cohort, the fasting
      posthepatic insulin delivery rate [IDR, obtained as the product of clamp-derived
      posthepatic insulin MCR and fasting plasma insulin concentration] was 8.9 (6.6)
      mU/min (median and interquartile range), and it gradually increased with age. In
      univariate association, IDR was positively related to body mass index (P <
      0.0001), fasting plasma glucose (P < 0.01), and waist-to-hip ratio (P < 0.001),
      and negatively related to insulin sensitivity (P < 0.0001). After controlling for
      these factors in a multivariate model, IDR declined significantly with age (P <
      0.0001). This intrinsic effect of age on IDR was similar in men and women, and it
      averaged 25% between 18-85 yr. In the same statistical model, insulin MCR (but
      not fasting plasma insulin concentration) showed a significant (P < 0.0001)
      inverse relation to age. We conclude that, in nondiabetic Caucasian subjects of
      either sex, senescence per se is associated with a progressive decline in both
      insulin clearance and basal insulin release.

PMID- 10084563
TI  - Can changes in plasma insulin concentration explain the variability in leptin
      response to weight loss in obese women with normal glucose tolerance?
AB  - The aim of this study was to test the hypothesis that the fall in circulating
      insulin concentration associated with moderate weight loss determines the
      associated decrease in plasma leptin concentration. For this purpose, 12 healthy,
      nondiabetic, obese women were studied before and after an average weight loss of
      9.5 kg (11.2% of initial body weight). Plasma leptin concentrations fell from a
      mean (+/-SE) value of 35 +/- 3 to 17 +/- 2 ng/mL (P < 0.001) in association with
      the loss of weight. However, there was no correlation between the decline in
      leptin concentration and the associated fall in weight, body mass index, fat
      mass, or percent body fat. Furthermore, no correlation was seen among changes in
      fasting plasma glucose or insulin concentrations, the 8-h integrated plasma
      glucose response to breakfast and lunch, or the estimate of insulin-mediated
      glucose disposal. The only measured variable that correlated with the fall in
      plasma leptin concentration (r = 0.78; P < 0.005) was the decline in the 8-h
      integrated plasma insulin response after weight loss (from 304 +/- 44 to 232 +/-
      36 microU/8 h x mL; P < 0.001). Finally, multivariate regression analysis, using
      various estimates of degree of obesity, insulin resistance, integrated glucose
      response, and integrated insulin response as dependent variables, indicated that
      only the insulin response was independently related to the decrease in leptin
      concentration (P = 0.035). The fall in integrated insulin response accounted for
      66% of the variance in leptin concentrations after weight loss, and this was true
      no matter what the estimate of change in degree of obesity. In addition to
      offering an explanation for the variance in postweight loss leptin
      concentrations, these data provide further evidence of the importance of ambient
      insulin concentrations in the regulation of plasma leptin concentrations.

PMID- 10084564
TI  - Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating.
AB  - Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea
      (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be
      stress induced. However, mounting evidence points to a metabolic/nutritional
      insult that may be the primary causal factor. We explored the thyroid, hormonal,
      dietary, behavior, and leptin changes that occur in FHA, as they provide a clue
      to the etiology of this disorder. Fourteen cycling control and amenorrheic
      nonathletic subjects were matched for age, weight, and height. The amenorrheic
      subjects denied eating disorders; only after further, detailed questioning did we
      uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic
      subjects demonstrated scores of abnormal eating twice those found in normal
      subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also
      expended more calories in aerobic activity per day and had higher fiber intakes
      (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4
      (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant
      change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not
      significantly, whereas leptin values were significantly lower (P < 0.05). Bone
      mineral density was significantly lower in the wrist (P < 0.05), with a trend to
      lower BMD in the spine (P < 0.08). Scores of emotional distress and depression
      did not differ between groups. The alterations in eating patterns, leptin levels,
      and thyroid function present in subjects with FHA suggest altered nutritional
      status and the suppression of the hypothalamic-pituitary-thyroid axis or the
      alteration of feedback set-points in women with FHA. Both lower leptin and
      thyroid levels parallel changes seen with caloric restriction. Nutritional
      issues, particularly dysfunctional eating patterns and changes in thyroid
      metabolism, and/or leptin effects may also have a role in the metabolic signals
      suppressing GnRH secretion and the pathogenesis of osteopenia despite normal body
      weight. These findings suggest that the mechanism of amenorrhea and low leptin in
      these women results mainly from a metabolic/nutritional insult.

PMID- 10084565
TI  - Out-patient screening for Cushing's syndrome: the sensitivity of the combination
      of circadian rhythm and overnight dexamethasone suppression salivary cortisol
      tests.
AB  - Screening tests have been used to support a biochemical diagnosis of Cushing's
      syndrome (CS). Measurements of salivary cortisol offer facilities for studying
      out-patients. This study assessed salivary cortisol in screening for CS by
      evaluating hypercortisolism based on circadian rhythm and the overnight 1-mg
      dexamethasone (DEX) suppression test for out-patients. We evaluated 33 patients
      with CS. Thirty normal volunteers and 18 obese patients were used as controls.
      Salivary cortisol (nanograms per dL) levels (mean +/- SEM) were 596 +/- 44, 528
      +/- 104, and 1205 +/- 118 (0900 h); 213 +/- 27, 325 +/- 76, and 778 +/- 74 (1700
      h); and 95 +/- 8, 133 +/- 26, and 914 +/- 94 (2300 h) in normal controls, obese
      subjects, and CS patients, respectively. After the overnight 1-mg DEX test, they
      were 64 +/- 1.1, 107 +/- 25, and 1048 +/- 129, respectively. In the present
      series, a single out-patient 0900, 1700, and 2300 h measurement and an overnight
      1-mg DEX salivary cortisol level above the 90th percentile of the control or
      obese group values had sensitivities of 65.6%, 81.8%, 100%, and 100% or 78.1%,
      57.6%, 93.3%, and 91.4%, respectively. The sensitivity improved (100%) in
      response to the combination of 2300 h and overnight 1-mg DEX salivary cortisol
      suppression tests to differentiate between obese and CS subjects. Our data
      indicate that nighttime sample and overnight 1-mg DEX suppression salivary
      cortisol tests are sensitive markers for the diagnosis of CS. In addition, the
      combination of the two tests improves the ability to differentiate between obese
      and CS patients and may be useful for out-patient screening.

PMID- 10084566
TI  - Short-term fasting suppresses leptin and (conversely) activates disorderly growth
      hormone secretion in midluteal phase women--a clinical research center study.
AB  - Short term fasting activates the corticotropic and somatotropic, and suppresses
      the reproductive, axis in men. Analogous neuroendocrine responses are less well
      characterized in women. Recently, we identified a negative association between
      the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH
      secretion in older fed women. In the present study, we investigated the impact of
      acute nutrient deprivation on pulsatile GH and LH secretion and mean leptin
      concentrations in eight healthy young women in the sex-steroid replete milieu of
      the midluteal phase of the normal menstrual cycle. Volunteers underwent 24-h
      blood sampling during randomly ordered, short term (2.5-day), fasting vs. fed
      sessions in separate menstrual cycles. Pulsatile GH and LH secretion over 24 h
      was quantified by deconvolution analysis, nyctohemeral rhythmicity was quantified
      by cosinor analysis, and the orderliness of the GH or LH release process was
      quantified by the approximate entropy statistic. By paired statistical analysis,
      a 2.5-day fast failed to alter mean (pooled) 24-h serum concentrations of LH,
      progesterone, estradiol, or PRL, but increased cortisol levels more than 1.5-fold
      (P = 0.0003). Concurrently, mean (pooled) serum leptin concentrations fell by 75%
      (P = 0.0003), and insulin-like growth factor I (IGF-I; P < 0.05) and insulin
      decreased significantly (P = 0.0018). In contrast, the daily pulsatile GH
      secretion rate rose 3-fold (P < 0.001). Amplified daily GH secretion was
      attributable mechanistically to a 2.3-fold rise in GH secretory burst mass,
      reflecting an increased GH secretory burst amplitude (P < 0.01). The GH half
      life, duration of GH secretory bursts, and GH pulse frequency did not vary during
      short term fasting. The disorderliness of GH release increased significantly with
      nutrient restriction (P = 0.005). The mesor and amplitude of the nyctohemeral
      serum GH concentration rhythm also rose with fasting (P < 0.01), but the timing
      of maximal serum GH concentrations did not change. Thus, short-term (2.5-day)
      fasting during the sex steroid-replete midluteal phase of the menstrual cycle in
      healthy young women profoundly suppresses 24-h serum leptin and insulin (and to a
      lesser degree, IGF-I) concentrations, augments cortisol release, but fails to
      alter daily LH, estradiol, or progesterone concentrations. In contrast, the GH
      axis exhibits strikingly amplified pulsatile secretion, increased nyctohemeral
      rhythmicity, and marked disorderliness of the release process. We conclude that
      the somatotropic axis is more evidently vulnerable to short-term nutrient
      restriction than the reproductive axis in steroidogenically sufficient midluteal
      phase women. This study invites the question of whether normal (nutritionally
      replete) GH secretory dynamics can be restored in fasting women by human leptin,
      insulin, or IGF-I infusions.

PMID- 10084567
TI  - Isoflavones from red clover improve systemic arterial compliance but not plasma
      lipids in menopausal women.
AB  - The possibility that the heightened cardiovascular risk associated with the
      menopause can be reduced by increasing dietary isoflavone intake was tested in 17
      women by measuring arterial compliance, an index of the elasticity of large
      arteries such as the thoracic aorta. Compliance diminishes with age and
      menopause. An initial 3- to 4-week run-in period and a 5-week placebo period were
      followed by two 5-week periods of active treatment with 40 mg and then 80 mg
      isoflavones derived from red clover containing genistein, daidzein, biochanin,
      and formononetin in 14 and 13 women, respectively, with 3 others serving as
      placebo controls throughout. Arterial compliance, measured by ultrasound as a
      pressure (carotid artery) and volume (outflow into aorta) relationship, was
      determined after each period; plasma lipids were measured twice during each
      period. Urinary output of isoflavones was also determined. Arterial compliance
      rose by 23% relative to that during the placebo period with the 80-mg isoflavone
      dose and slightly less with the 40-mg dose (mean +/- SEM: placebo, .197 +/- .015;
      40 mg, .237 +/- 0.007; 80 mg, .244 +/- .014). In the three women receiving
      continuous placebo, compliance was .16 +/- .022, similar to that during the run
      in period for the remaining subjects (.17 +/- .021) [corrected]. ANOVA showed a
      significant (P = < 0.001) difference between treatments; by Bonferroni multiple
      comparisons and by paired t test, differences were significant between placebo
      and 40- and 80-mg isoflavone doses (by paired t test: P = 0.039 for placebo vs.
      40 mg; P = 0.018 for placebo vs. 80 mg). Plasma lipids were not significantly
      affected. An important cardiovascular risk factor, arterial compliance, which
      diminishes with menopause, was significantly improved with red clover
      isoflavones. As diminished compliance leads to systolic hypertension and may
      increase left ventricular work, the findings indicate a potential new therapeutic
      approach for improved cardiovascular function after menopause.

PMID- 10084568
TI  - Longitudinal study of leptin concentrations during puberty: sex differences and
      relationship to changes in body composition.
AB  - Leptin may have a role in the initiation of puberty and the regulation of
      subsequent weight gain, but this hypothesis has not been tested by longitudinal
      study. We report data from 40 normal children (20 boys and 20 girls) followed
      from 8-16 yr of age with hormone measurements and auxology every 6 months. Before
      the onset of puberty, leptin levels were similar in boys and girls: G1, mean (95%
      confidence interval), 2.63 (2.17-3.20) ng/mL; B1, 2.47 (2.08-2.94) ng/mL (P =
      0.64) and increased with age in both sexes (B, 0.107 +/- 0.042; P = 0.02). With
      the onset of puberty, leptin levels increased in girls (B2-B5, P < 0.0005), but
      decreased in boys (G2-G5, P < 0.0005). Similar positive independent relationships
      were seen between leptin and fat mass in girls (B, 0.106 +/- 0.022; P < 0.0005)
      and boys (B, 0.121 +/- 0.020; P < 0.0005), and negative relationships were found
      with fat-free mass [girls: B, -1.104 +/- 0.381 (P < 0.005); boys: B, -1.288 +/-
      0.217 (P < 0.0005)]. Girls gained more fat mass than boys, whereas boys gained
      more fat-free mass, and this explained the sex difference in leptin levels.
      Leptin levels correlated significantly with a large number of other hormones, but
      none was independent of changes in body composition. In girls, but not in boys,
      low leptin levels during prepuberty (B1) predicted subsequent gains in the
      percent body fat during puberty (r = -0.75; P = 0.005). The sexual dimorphism in
      leptin levels during puberty reflects differential changes in body composition.
      Prepubertal leptin levels in girls also predict gains in the percent body fat.

PMID- 10084569
TI  - Pubertal African-American girls expend less energy at rest and during physical
      activity than Caucasian girls.
AB  - Between 1963 and 1991, the most dramatic increases in the prevalence of
      overweight in the United States have been reported in African-American girls.
      Lower basal energy expenditure and lack of physical activity are believed to be
      risk factors for excessive weight gain. We hypothesized that energy expenditure
      at rest and during physical activity are lower in pubertal African-American girls
      than in Caucasian girls. Basal metabolic rate and sleeping energy expenditure of
      40 Caucasian and 41 African-American pubertal girls (matched for age, physical
      characteristics, body fat, and energy intake) were measured by whole-room
      calorimetry, energy expended for physical activity by the doubly labeled water
      method, sexual maturity by physical examination, body composition by dual-energy
      x-ray absorptiometry, physical fitness by treadmill testing, and energy intake by
      3-day food record. After adjusting for soft lean tissue mass, the basal energy
      expenditure (1333 +/- 132 vs. 1412 +/- 132 kcal/day, P = 0.01) and energy
      expended for physical activity (809 +/- 637 vs. 1271 +/- 162 kcal/day, P < 0.01)
      were significantly lower in the African-American girls than in the Caucasian
      girls. The differences remained the same after controlling for differences in
      sexual maturity and/or physical fitness. The lower energy expenditure of the
      pubertal African-American girls suggests that they are at a higher risk of
      becoming overweight than their Caucasian counterparts.

PMID- 10084570
TI  - Lithium as a potential adjuvant to 131I therapy of metastatic, well
      differentiated thyroid carcinoma.
AB  - As lithium inhibits the release of iodine from the thyroid but does not change
      iodine uptake, it may potentiate 131I therapy of thyroid cancer. The effects of
      lithium on the accumulation and retention of 131I in metastatic lesions and
      thyroid remnants were evaluated in 15 patients with differentiated thyroid
      carcinoma. Two 131I turnover studies were performed while the patients were
      hypothyroid. One was performed while the patient received lithium; the second
      served as a control study. From a series of gamma-camera images, it was found
      that lithium increased 131I retention in 24 of 31 metastatic lesions and in 6 of
      7 thyroid remnants. A comparison of 131I retention during lithium with that
      during the control period showed that the mean increase in the biological or
      retention half-life was 50% in tumors and 90% in remnants. This increase occurred
      in at least 1 lesion in each patient and was proportionally greater in lesions
      with poor 131I retention. When the control biological half life was less than 3
      days, lithium prolonged the effective half-life, which combines both biological
      turnover and isotope decay, in responding metastases by more than 50%. More 131I
      also accumulated during lithium therapy, probably as a consequence of its effect
      on iodine release. The increase in the accumulated 131I and the lengthening of
      the effective half-life combined to increase the estimated 131I radiation dose in
      metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest
      that lithium may be a useful adjuvant for 131I therapy of thyroid cancer,
      augmenting both the accumulation and retention of 131I in lesions.

PMID- 10084571
TI  - Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone
      receptor gene.
AB  - Isolated growth hormone (GH) deficiency (IGHD) is a rare cause of short stature.
      The same mutation of the gene encoding the growth hormone-releasing hormone
      receptor (GHRHR) has been identified as the basis for IGHD in three families from
      the Indian subcontinent. The prevalence and heterogeneity of defects in the GHRHR
      gene are not known. Twenty-two dwarf members of a large, extended kindred
      containing at least 105 affected members with autosomal recessive short stature
      underwent extensive endocrine evaluation, which confirmed markedly reduced or
      undetectable serum concentrations of GH that did not increase in response to
      different stimuli. DNA sequences of the 13 exons and intron-exon boundaries of
      the GHRHR gene were determined in an index patient. A novel homozygous 5' splice
      site mutation (G-->A at position +1) in IVS1 was found. Thirty of the affected
      subjects tested were homozygous for this mutation, and 64 clinically unaffected
      patients were either heterozygous for the mutation (n = 41, including 9 obligate
      carriers) or homozygous for the wild-type sequence (n = 23). We describe a novel
      mutation in the GHRHR gene as cause of dwarfism in the largest kindred with
      familial IGHD described to date.

PMID- 10084572
TI  - Evaluation of the adequacy of levothyroxine replacement therapy in patients with
      central hypothyroidism.
AB  - As there are few data on the evaluation of the adequacy of levothyroxine (L-T4)
      therapy in patients with central hypothyroidism (CH), a prospective study was
      performed to assess the accuracy of various parameters in the follow-up of 37 CH
      patients. Total and free thyroid hormones, TSH, and a series of clinical and
      biochemical indexes of peripheral thyroid hormone action have been evaluated off
      and on L-T4 therapy. Samples were taken before the daily administration of L-T4.
      In all patients off therapy, clinical hypothyroidism and low levels of free T4
      (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the
      normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of
      thyroid hormone action were significantly modified after L-T4 withdrawal and
      exhibited significant correlation with free thyroid hormone levels. During L-T4
      replacement therapy, 32 patients had circulating levels of FT4 and FT3 and
      indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3
      microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of
      FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations,
      suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated
      undertreatment in 2 patients. The clinical parameters lack the required
      specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose
      should be established, taking into account the weight, the age, and the presence
      of other hormone deficiencies or pharmacological treatment of CH patients. In
      conclusion, our results indicate that the diagnosis of CH is reached at best by
      measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4
      replacement therapy, both FT4 and FT3 serum levels together with some biochemical
      indexes of thyroid hormone action are all necessary to a more accurate disclosure
      of over- or undertreated patients.

PMID- 10084573
TI  - Normal female infants born of mothers with classic congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency.
AB  - Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency,
      especially those patients with the salt-losing form, have decreased fertility
      rates. Pregnancy experience in this population is limited. We report the
      pregnancy outcomes and serial measurements of maternal serum steroid levels in
      four women with classic 21-hydroxylase deficiency, three of whom were female
      pseudohermaphrodites with the salt-losing form. These glucocorticoid-treated
      women gave birth to four healthy female newborns with normal female external
      genitalia, none of whom were affected with 21-hydroxylase deficiency. In three
      women, circulating androgen levels increased during gestation, but remained
      within the normal range for pregnancy during glucocorticoid therapy. In the
      fourth patient, androgen levels were strikingly elevated during gestation despite
      increasing the dose of oral prednisone from 5 to 15 mg/day (two divided doses).
      Notwithstanding the high maternal serum concentration of androgens, however,
      placental aromatase activity was sufficient to prevent masculinization of the
      external genitalia of the female fetus and quite likely the fetal brain,
      consistent with the idea that placental aromatization of androgens to estrogens
      is the principal mechanism that protects the female fetus from the masculinizing
      effects of maternal hyperandrogenism. These four patients highlight key issues in
      the management of pregnancy in women with 21-hydroxylase deficiency, particularly
      the use of endocrine monitoring to assess adrenal androgen suppression in the
      mother, especially when the fetus is female. Recommendations for the management
      of pregnancy and delivery in these patients are discussed.

PMID- 10084574
TI  - Hyperenterostatinemia in premenopausal obese women.
AB  - Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala
      Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of
      procolipase after tryptic cleavage and belong to the family of gut-brain
      peptides. Although enterostatin-like immunoreactivities exist in blood, brain,
      and gut, and exogenous enterostatins decrease fat appetite and insulin secretion
      in rats, the roles of these peptides in human obesity remain to be examined. To
      determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR
      and APGPR levels were measured in 38 overnight-fasted subjects (body mass index,
      17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of
      lean subjects was significantly lower than that in obese subjects [lean = 603 +/-
      86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In
      addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was
      significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n =
      17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies
      show hyperenterostatinemia in obesity and a diminution in enterostatin secretion
      after satiety.

PMID- 10084575
TI  - Longitudinal hormonal and pituitary imaging changes in two females with combined
      pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene.
AB  - Genomic DNA from 18 patients with combined pituitary hormone deficiency was
      screened for 2-bp deletion (A301,G302) in PROP1 gene by BcgI restriction
      endonuclease analysis of PCR-amplified exon 2 gene fragments. Two unrelated
      female patients were homozygous for this 2-bp deletion. Patient 1 presented at
      8.8 yr with severe short stature (-2.9 SD score), slightly enlarged sella turcica
      at x-rays, and diffusely enlarged pituitary gland (height, 8 mm vs. 4.5 +/- 0.6
      mm in matched controls) with hyperintense enhanced signal at T1 weighted image at
      coronal and sagittal views at magnetic resonance imaging (MRI). MRI repeated at
      age 15 yr revealed a marked reduction of pituitary height (2 mm vs. 5.3 +/- 0.8
      mm in matched controls). Patient 2 presented at 27 yr with short stature (-5.5 SD
      score) without pubertal development, normal sella turcica, and a pituitary gland
      of reduced size (height, 5 mm vs. 6.1 +/- 0.3 mm in matched controls) of normal
      intensity at MRI. Both patients had normal pituitary stalk and normally located
      neurohypophysis. Hormonal features were characterized by GH, TSH, PRL, LH, and
      FSH deficiencies. Patient 1 had normal cortisol secretion at 8.8 yr, and at 16.6
      yr had developed partial cortisol deficiency, whereas patient 2 maintained normal
      cortisol secretion at 28.4 yr. We conclude that 1) a large sella turcica and an
      enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI
      can be suggestive of PROP1 deficiency; 2) pituitary morphology can change during
      follow-up of patients with PROP1 gene mutation; and 3) hormonal deficiencies
      could include the adrenal axis.

PMID- 10084576
TI  - Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic
      ovary syndrome is not predicted by the basal dehydroepiandrosterone sulfate
      level.
AB  - Adrenal androgen (AA) excess, primarily in the form of dehydroepiandrosterone
      sulfate (DHEAS), affects over 50% of women with the polycystic ovary syndrome
      (PCOS). Nonetheless, it is unclear what role AA excess plays in the PCOS
      associated oligo-ovulation. We have hypothesized that AAs are important in the
      maintenance of the ovulatory dysfunction of women with PCOS and AA excess, which
      can be improved by glucocorticoid suppression. To test our hypothesis we
      prospectively studied 36 unselected women, ages 18-40 yr, with PCOS; i.e.
      oligomenorrhea (cycles > 35 days in length), and clinical/ biochemical evidence
      of hyperandrogenism (i.e. hirsutism and/or hyperandrogenemia), after the
      exclusion of related disorders. After informed consent, all patients underwent an
      acute ACTH-(1-24) stimulation test, measuring androstenedione,
      dehydroepiandrosterone (DHEA) and cortisol (F), and were then treated with
      dexamethasone 0.5 mg/day for four cycles. Ovulatory function was assessed before
      and during treatment using a basal body temperature calendar and day 22-24
      progesterone (P4) levels. If patients were anovulatory (P4 < 4 ng/mL), a
      withdrawal bleed was induced by the administration of 100 mg P4 in oil i.m.
      Before and during treatment the levels of total and free testosterone (T), sex
      hormone-binding globulin, androstenedione, DHEA, DHEAS, cortisol, luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) were monitored. With therapy,
      all patients demonstrated a significant decrease in all androgens (-40-60%), a
      24% increase in sex hormone-binding globulin, and no change in LH/FSH. Mean body
      weight increased by over 4 kg (4.4%) during treatment. Of the 138 cycles
      monitored, 78% remained anovulatory. Twenty-five percent, 17%, 14%, and 20% of
      the first, second, third, and fourth treatment cycles, were ovulatory,
      respectively (P = 0.381). Of the 36 patients studied, 18 (50%) did not
      demonstrate a single ovulatory cycle (i.e. a day 22-24 P4 level > 4 ng/mL); and
      of the remaining, 10 (28%) had only one, five (14%) had two, and three (8%) had
      three ovulatory cycles. There were no significant differences either in physical
      features, basal hormones, adrenal response to ACTH stimulation, or hormonal
      levels at the end of treatment, between those women ovulating and those not.
      Finally, there were no differences in ovulatory response to dexamethasone therapy
      between women with (n = 14) and without (n = 22) DHEAS excess (i.e. DHEAS > 2750
      ng/mL). In conclusion, the data from this prospective study do not suggest that
      continuous dexamethasone suppression results in consistent ovulation in any PCOS
      patient, regardless of basal DHEAS levels. Furthermore, this treatment is
      associated with significant side-effects, notably weight gain. Finally, these
      data suggest that, while AA may be an important risk factor for PCOS, once the
      syndrome is established, they play a limited role in the associated ovulatory
      dysfunction.

PMID- 10084577
TI  - Preoperative diagnosis of medullary thyroid carcinoma by RT-PCR using RNA
      extracted from leftover cells within a needle used for fine needle aspiration
      biopsy.
AB  - Fine needle aspiration Biopsy (FNAB) is commonly used to diagnose thyroid tumors.
      In some clinical situations, however, accurate diagnosis requires a more
      objective method than cytological examination alone. Medullary thyroid carcinomas
      (MTC) derive from C cells in the thyroid and express some specific messenger RNAs
      (mRNA), such as those transcribed from the RET proto-oncogene, the calcitonin
      gene, and the gene for carcinoembryonic antigen (CEA), which usually do not exist
      in normal thyroid follicular cells or thyroid tumors of follicular epithelial
      descent. Recently, we established a new method for the molecular diagnosis of
      thyroid tumors without additional invasion to the patient by extracting RNA for
      RT-PCR from the leftover cells inside the needles used for fine needle aspiration
      biopsy (Aspiration Biopsy-Reverse Transcription-Polymerase Chain Reaction, ABRP).
      By applying the ABRP method to the detection of RET, calcitonin, and CEA mRNAs,
      an accurate molecular-based diagnosis for MTC maybe established as an adjunct to
      cytological diagnosis. In this study, 35 aspirates were obtained at the time of
      surgery from thyroid tumors, including 11 MTCs. The expression of these mRNAs in
      the leftover cells inside the needles used for the aspiration was then examined.
      Transcripts from all three genes were detected in the samples from all 11 MTCs,
      but none of these mRNAs were detected in the other tumors or normal thyroid
      tissues. Furthermore, MTC was preoperatively diagnosed in three patients by ABRP
      detection of these mRNAs, and these diagnoses were confirmed by subsequent
      cytological and histopathological analyses. Thus RT-PCR detection of RET,
      calcitonin, and CEA mRNAs in FNABs may be an efficient molecular adjunct for
      diagnosing MTC.

PMID- 10084578
TI  - Selective lack of growth hormone (GH) response to the GH-releasing peptide
      hexarelin in patients with GH-releasing hormone receptor deficiency.
AB  - The mechanism of the synergistic relationship between GH-releasing peptide (GHRP)
      and GHRH with respect to GH secretion is poorly understood. We report the
      response to hexarelin, a potent GHRP, in patients affected with a homozygous
      mutation in the GHRH receptor gene, with consequent GHRH resistance and GH
      deficient dwarfism. This newly described syndrome is the human homolog of the
      little (lit/lit) mouse. Intravenous administration of hexarelin (2 microg/kg) to
      four male adult patients (dwarfs of Sindh) resulted in a complete lack of
      elevation in plasma GH levels (< 1 ng/mL), an at least 50- to 100-fold deviation
      from the normal response. In contrast, plasma PRL, ACTH, and cortisol levels rose
      in a normal manner in response to hexarelin. We conclude that an intact GHRH
      signaling system is critical for GHRPs to exert their effect on GH release, but
      that the GHRH system is not necessary for the effect of GHRP on PRL and ACTH
      secretion. Hexarelin (and probably other GHRPs) are not effective agents for the
      treatment of patients with GHRH resistance due to GHRH receptor deficiency.

PMID- 10084579
TI  - Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in
      neonatal screening for congenital adrenal hyperplasia.
AB  - We investigated the feasibility and diagnostic utility of genotyping 9 CYP21
      mutations, linked chromosome 6p markers, and a dimorphic X-Y marker from neonatal
      screening samples. Blood-impregnated filter papers (Guthrie cards) from 603
      randomly chosen New Zealand neonates were genotyped blind to 17
      hydroxyprogesterone (17-OHP) levels. Another 50 samples from Swiss and North
      American infants with correlative hormonal data were also genotyped. DNA was
      extracted, and gene-specific PCR was performed. CYP21 PCR products were subjected
      to ligase detection reaction, simultaneously analyzing 9 CYP21 mutations; PCR
      products of other genes were subjected to direct gel analysis. CYP21 genotyping
      indicated a heterozygote rate of 2.8% for classic mutations (excluding CYP21
      deletions), and 2.0% for nonclassic mutations in New Zealanders. Ten full-term
      affected neonates showed a wide range of 17-OHP levels (15-1400 nmol/L). Sick or
      preterm infants or infants screened on the first day of life with high 17-OHP
      proved genetically unaffected. Genetic linkage disequilibrium was found between
      two CYP21 mutations and chromosome 6p markers. Guthrie cards can be used to
      accurately genotype CYP21 and other relevant markers, potentially enhancing the
      specificity and sensitivity of congenital adrenal hyperplasia screening. CYP21
      heterozygote frequency for classic mutations is higher than expected based on
      genotype compared with that predicted by hormonal newborn screening.

PMID- 10084580
TI  - Long-term treatment with growth hormone has no persisting effect on
      lipoprotein(a) in patients with Turner's syndrome.
AB  - Treatment with recombinant human GH (rhGH), alone or in combination with the
      anabolic steroid oxandrolone (OX), has been recommended for girls with Turner's
      syndrome to improve final height. Several cardiovascular risk factors have been
      described in patients with Turner's syndrome, but the effect of therapy with rhGH
      and OX on lipoprotein(a) [Lp(a)] has not been investigated. Lp(a) serum levels
      and apolipoprotein(a) phenotypes were determined in 46 girls with Turners
      syndrome (aged 6-15 yr) during treatment with different combinations of rhGH and
      OX for 24-36 months (median, 27 months). Lp(a) serum levels showed little
      variation during 30 months of treatment in all treatment groups. Lp(a) levels
      showed no significant change in 25 patients receiving only rhGH and in 21
      patients receiving rhGH and OX in combination. Treatment effects were independent
      of apolipoprotein(a) phenotypes and were not influenced by pubertal status. These
      data indicate that long term administration of rhGH has no significant impact on
      serum Lp(a) levels in girls with Turner's syndrome.

PMID- 10084581
TI  - Androgens and osteocalcin during the menstrual cycle.
AB  - The relationship between physiological variations in female sex and androgenic
      hormones and calciotropic hormones was investigated during the menstrual cycle.
      Estradiol, progesterone, total and free testosterone, androstenedione,
      immunoreactive PTH, calcitonin, osteocalcin (OC), and ionized calcium serum
      levels were determined throughout the menstrual cycle in a population of healthy
      eumenorrhoic women (n = 12; age range: 20-29 yr; mean: 24.2 yr). The women were
      studied from the first day of a menstrual phase until the first day of the
      following menstrual phase. Cycle length was standardized on the preovulatory
      estradiol peak (day 0), and values were given for the first day of a menstrual
      phase, and days -12, -10, -8, -6, -4, -2, 0, 2, 4, 6, 8, 10, 12, and 14 of the
      menstrual cycle. All subjects had a regular ovulatory cycle, as indicated by the
      hormonal profile. No significant cycle phase-dependent changes in calciotropic
      hormones were present. Significant positive correlations between total
      testosterone (r = 0.32, P < 0.001), free testosterone (r = 0.26, P < 0.001),
      androstenedione (r = 0.35, P < 0.0001), and OC were observed. The significant
      relations between these variables were confirmed by a time series analysis. For
      the first time, these findings indicate a relationship between androgens and OC
      serum levels during the menstrual cycle. An important regulatory role of
      endogenous androgens in OC secretion, bone formation, and maintenance of normal
      bone mineral content in the healthy eumenorrhoic woman is hence suggested.

PMID- 10084582
TI  - Diurnal rhythm of testosterone secretion before and throughout puberty in healthy
      girls: correlation with 17beta-estradiol and dehydroepiandrosterone sulfate.
AB  - The regulation of androgen synthesis during puberty in females is complicated,
      with changes in steroidogenic and peripheral interconversion capacity. In the
      present study we have investigated the diurnal rhythm of testosterone secretion
      in 56 healthy girls before and during puberty, up to 2 yr postmenarche. The
      girls' ages ranged between 4.6-16.5 yr, and their height SD scores ranged between
      -3.6 and +3.7. One to 5 serum profiles (seven samples per 24 h) were taken from
      each girl for steroid measurements, and a total of 84 serum profiles were
      obtained. Serum testosterone concentrations were determined using a RIA with a
      detection limit of 30 pmol/L. The results demonstrate that there is a diurnal
      rhythm of testosterone secretion during both prepuberty and puberty in girls. The
      pattern has its nadir in the late evening or just after midnight, with the
      highest levels in the morning (0600-1000 h). Serum testosterone concentrations in
      prepubertal girls were significantly lower than those in pubertal girls and were
      significantly lower in early puberty than in girls in mid- or late puberty. No
      differences were found in levels between girls in midpuberty or late puberty.
      Before puberty, serum testosterone concentrations correlated with serum
      dehydroepiandrosterone sulfate, consistent with the adrenals being the major
      source of testosterone. After the onset of puberty, a correlation between
      testosterone and 17beta-estradiol was seen, consistent with the ovaries being the
      major source of testosterone during puberty. Furthermore, the present study
      showed that there is a relative hyperandrogenicity in early puberty, with high
      levels of androgens relative to estrogens.

PMID- 10084583
TI  - Relationship between serum estradiol levels and the increases in high-density
      lipoprotein levels in postmenopausal women treated with oral estradiol.
AB  - Postmenopausal women are prescribed a standard dose of estrogen, which is optimal
      for a population but not for all individuals. We wished to identify if an
      individual's estradiol level can indicate the minimum effective dose of estrogen
      which maximally increases high-density lipoprotein (HDL) levels, which could be
      cardioprotective. We performed a prospective, double-blind crossover study in 19
      healthy postmenopausal women, receiving three treatments in random order for 9
      weeks each: a) placebo, b) 1 mg oral estradiol daily, and c) 2 mg oral estradiol
      daily. Lipoprotein and estradiol (E2) levels were measured 10-12 h after pills
      were taken. E2 levels with 1 mg estradiol were positively correlated with the
      increases in HDL levels (r = 0.70, P < 0.01). Only the eight subjects who had E2
      levels < 50 pg/mL after 1 mg estradiol treatment demonstrated further increases
      in HDL levels by increasing the daily dose to 2 mg (by 3 +/- 5% with 1 mg
      estradiol and by 13 +/- 7% with 2 mg). The other 11 subjects who had E2 levels >
      50 pg/mL with 1 mg estradiol had no additional benefit from increasing the
      estradiol dose (HDL increased by 13 +/- 9% with 1 mg, and by 17 +/- 10% with 2
      mg). Thus, measurement of an E2 level the morning after taking 1 mg estradiol at
      bedtime identifies who may benefit from improvement in HDL levels by increasing
      to a 2-mg dose.

PMID- 10084584
TI  - Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile
      GnRH administration.
AB  - We have studied a kindred with three siblings with isolated hypogonadotropic
      hypogonadism caused by compound heterozygote mutations in the GnRH receptor gene.
      The disorder was transmitted as an autosomal recessive trait. The R262Q mutation
      in intracellular loop 3 of the receptor was associated with a mutation in the
      third transmembrane domain of the receptor, A129D, that has never been described
      before. This A129D mutation results in a complete loss of function, indicated by
      the lack of inositol triphosphate (TP3) 3 production by transfected Chinese
      hamster ovary (CHO) cells after GnRH stimulation. The two brothers had
      microphallus and bilateral cryptorchidism and were referred for lack of puberty,
      whereas their sister had primary amenorrhea and a complete lack of puberty. Their
      basal gonadotropin concentrations were below the reference range, and their
      endogenous LH secretory patterns were abnormal, with a low-normal frequency of
      small pulses or no apparent LH pulse. Pulsatile GnRH administration (10
      microg/pulse every 90 min for 40 h) resulted in increased mean LH without any
      significant changes in testosterone levels in the two brothers, whereas the LH
      secretory profile of their sister remained apulsatile. Larger pulses of exogenous
      GnRH (20 microg every 90 min for 24 h) caused the sister to produce recognizable
      low amplitude LH pulses. The concentrations of free alpha-subunit significantly
      increased in all patients during the pulsatile GnRH administration. Thus, these
      hypogonadal patients are partially resistant to pulsatile GnRH administration,
      suggesting that they should be treated with gonadotropins to induce
      spermatogenesis or ovulation rather than with pulsatile GnRH.

PMID- 10084585
TI  - Secretion of testosterone and its delta4 precursor steroids into spermatic vein
      blood in men with varicocele-associated infertility.
AB  - Insight into the mechanisms by which steroid hormones are released from the
      testes was sought by examining the concentrations of progesterone, 17alpha
      hydroxyprogesterone, and androstenedione as well as testosterone in spermatic
      vein blood every 15 min for 4 h in men with varicocele-associated infertility.
      Coincident discrete secretory episodes of all four steroids were found, and
      spermatic vein concentrations of testosterone were highly positively correlated
      to the concentrations of progesterone (r = 0.79), 17alpha-hydroxyprogesterone (r
      = 0.81), and androstenedione (r = 0.82), respectively. The sum of the four
      measured steroids per mL plasma was calculated, and testosterone was found to
      account for 70%, 17alpha-hydroxyprogesterone for 24%, androstenedione for 5%, and
      progesterone for 1% of the total. In a previous study of the intratesticular
      steroids in a separate population of men with varicocele-associated infertility,
      the sum of these four steroids per g tissue was similarly calculated.
      Testosterone accounted for 70% of the four measured steroids, 17alpha
      hydroxyprogesterone for 22%, androstenedione for 4%, and progesterone for 3% of
      the total. Thus, the relative concentrations of these four steroids are nearly
      identical in testicular tissue and spermatic vein plasma. From these data we
      hypothesize that steroids in the testicular interstitium are cosecreted into
      peripheral plasma in response to stimulation by LH and propose that the mechanism
      initiating this pulsatile mode of secretion oftestosterone and its precursor
      steroids may not be coupled to testosterone biosynthesis.

PMID- 10084586
TI  - Prevalence of variants in candidate genes for type 2 diabetes mellitus in The
      Netherlands: the Rotterdam study and the Hoorn study.
AB  - We have analyzed the association of variants in the genes for amylin, insulin
      receptor, insulin receptor substrate-1 (IRS-1), and coagulation factor V with
      type 2 diabetes mellitus. Random samples of subjects with type 2 diabetes and
      controls were taken from two population-based studies, the Hoorn and Rotterdam
      studies, to reduce the risk of artifactual associations. No association was found
      for variants in the genes for amylin, IRS-1, and coagulation factor V, nor was
      there any evidence for epistatic interactions between these gene variants. A
      significant difference in the frequency of the Arg972 allele of the IRS-1 gene
      was observed between control subjects from Hoorn and Rotterdam (9.4% vs. 18.6%; P
      < 0.05). The insulin receptor Met985 variant was found at frequencies of 4.4% and
      1.8%, respectively, in type 2 diabetic (n = 433) and normoglycemic patients (n =
      799; P < 0.02). Inclusion of data from two other studies yielded a summarized
      odds ratio of 1.87 (95% confidence interval, 1.06-3.29; P = 0.03). We conclude
      that the association between the Met985 variant in the insulin receptor gene and
      type 2 diabetes, which we previously reported in the Rotterdam study, is
      supported by thejoint analysis with a second population-based study and other
      studies. The large regional differences in allele frequency of the Arg972 allele
      of IRS-1 gene makes genetic association studies of this gene less reliable.

PMID- 10084587
TI  - Tissue composition affects measures of postabsorptive human skeletal muscle
      metabolism: comparison across genders.
AB  - Despite clear anthropomorphic differences, gender differences in human skeletal
      muscle protein and carbohydrate metabolism have not been carefully examined. We
      compared postabsorptive forearm glucose, oxygen, and lactate balances and forearm
      protein kinetics between 40 male and 36 female subjects. Forearm composition was
      measured in a subset of 17 subjects (8 males and 9 females) using multislice
      magnetic resonance imaging. Oxygen uptake, net phenylalanine release, and
      estimated rates of forearm protein synthesis and degradation were greater in male
      than in female subjects when expressed as the rate per 100 mL forearm volume (P <
      0.05). In males, however, muscle accounted for 58% of forearm volume, compared
      with 46% in females (P < 0.001). When phenylalanine balance, protein degradation
      and synthesis, and glucose and oxygen uptake were expressed per 100 mL forearm
      muscle, there were no significant differences across gender. Likewise, the
      extraction fractions for oxygen, glucose, phenylalanine, and labeled
      phenylalanine were comparable in males and females. We conclude that cross-gender
      comparisons of metabolic variables must accommodate differences in tissue
      composition. These data indicate that in the postabsorptive state, skeletal
      muscle metabolism of glucose, protein, and oxygen do not differ by gender in
      healthy young humans.

PMID- 10084588
TI  - Functional characterization of truncated growth hormone (GH) receptor-(1-277)
      causing partial GH insensitivity syndrome with high GH-binding protein.
AB  - We have previously reported a novel heterozygous donor splice site mutation in
      intron 9 of the GH receptor (GHR) gene in Japanese siblings who showed partial GH
      insensitivity and high serum GH-binding protein (GHBP) levels. This mutation
      caused the splicing abnormality and produced the truncated GHR consisting of 277
      amino acids (GHR-277), which lacked most of the intracellular domain of GHR,
      including both boxes 1 and 2. In this study, we have characterized the function
      of GHR-277 expression in COS-7 and CHO cells in vitro. Scatchard analysis
      revealed that GHR-277 possessed approximately 1.5 times higher affinity to GH and
      twice the number of binding sites compared to wild-type full-length GHR (GHR-fl).
      The GHBP level in culture medium of GHR-277-expressing cells was approximately 3
      times higher than that in GHR-fl-expressing cells. Interestingly, the ligand
      induced internalization of GHR-277 was significantly reduced compared with that
      of GHR-fl. Moreover, in GH-induced tyrosine phosphorylation of signal transducer
      and activator of transcription-5 (STAT5), GHR-277 exerted a dominant negative
      effect when GHR-277 and GHR-fl were cotransfected. These in vitro data would well
      explain the clinical characteristics in our patients showing high serum GHBP
      levels and development of short stature despite a heterozygous mutation of the
      GHR gene.

PMID- 10084589
TI  - Impact of architectural disruption on adrenocortical steroidogenesis in vitro.
AB  - The adrenal cortex is an architecturally complex tissue, with cellular zonation
      thought to determine steroidogenesis. The impact that disruption of this tissue's
      architecture has on steroidogenesis in vitro, particularly adrenal androgen (AA)
      production, is unclear. We hypothesized that the extent of architectural
      disruption during tissue preparation would impact the study results. To test this
      hypothesis, we compared adrenocortical steroidogenesis in freshly prepared tissue
      slices, minces, and cell suspensions. Normal human adrenals (n = 5, three males
      and two females, age range 17-43 yr) were obtained at the time of organ donation.
      The three adrenal tissue preparations were incubated in serum-free medium with 10
      microM pregnenolone substrate +/- 1 microM ACTH. The production of
      dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and
      cortisol in the media were measured by radioimmunoassay. Initial time course
      intubations using adrenals from a single donor generally demonstrated that minces
      and suspensions had a greater steroid production compared with slices. In another
      series of 6-hr incubations using adrenals from four donors, production of
      dehydroepiandrosterone sulfate was found to be quite sensitive to architectural
      disruption, i.e. slices less than minces less than suspensions (0.88 vs. 2.1 vs.
      3.0 microg/gm tissue, respectively, P < 0.0001). Alternatively, cortisol and
      androstenedione production was higher in minces compared with slices or
      suspensions (25.6 vs. 37.7 vs. 18.7 ng/gm tissue, P < 0.0028, and 254 vs. 709 vs.
      456 ng/gm tissue, P < 0.0042, respectively). Production of dehydroepiandrosterone
      was apparently not significantly affected by the type of tissue preparation (28.2
      vs. 22.2 vs. 31.2 ng/gm tissue, P < 0.297, respectively). It is unlikely that
      generalized tissue disruption alone accounted for the observed differences, as
      the trends among tissue preparations were not consistent among steroids. We
      conclude that the type of tissue preparation of fresh adrenal tissue impacts
      significantly on steroidogenesis in vitro.

PMID- 10084590
TI  - Cortisol metabolism in human obesity: impaired cortisone-->cortisol conversion in
      subjects with central adiposity.
AB  - For a given body mass index (BMI), mortality is higher in patients with central
      compared to generalized obesity. Glucocorticoids play an important role in
      determining body fat distribution, but circulating cortisol concentrations are
      reported to be normal in obese patients. Our recent studies show enhanced
      conversion of inactive cortisone (E) to active cortisol (F) through the
      expression of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in cultured
      omental adipose stromal cells; the autocrine production of F may be a crucial
      factor in the pathogenesis of central obesity. We have now analyzed F metabolism
      in subjects with BMIs between 20-25 kg/m2 (group A), 25-30 kg/m2 (group B), and
      more than 30 kg/m2 (group C; n 12 in each group; six males and six premenopausal
      females; aged 23-44 yr). Glucose/insulin were measured using a 75-g oral glucose
      tolerance test, and each subject had total body and regional fat (scapular,
      waist, hip, and thigh) quantified using dual energy x-ray absorptiometry. Urinary
      total F metabolites (measured by gas chromatography/mass spectrometry) were
      increased in subjects with obesity [group A, 11,176 +/- 1,530 microg/24 h (mean
      +/- SE); group C, 13,661 +/- 1,444], although not significantly so (P = 0.08).
      There was a significant reduction in the urinary tetrahydrocortisol (THF) +/-
      5alpha-THF/tetrahydrocortisone (THE) and the cortol/cortolone ratio in obesity
      (group A vs. C, 1.06 +/- 0.08 vs. 0.84 +/- 0.04 and 0.41 +/- 0.03 vs. 0.34 +/-
      0.03, respectively; both P < 0.05). Urinary free F (UFF) excretion was similar in
      all three groups, as was the UFF/urinary free E (UFE) ratio. The 0900 h
      circulating F, E, and ACTH pre- and postovernight 1-mg dexamethasone suppression
      values were similar in all three groups, but a reduction in the generation of
      serum F from dexamethasone-suppressed values after oral cortisone acetate (25 mg)
      was evident in both obese groups [e.g. 546 +/- 37 nmol/L in group A vs. 412 +/-
      40 in group B (P < 0.05) and 388 +/- 38 in group C (P < 0.01) 180 min post-E].
      Insulin resistance was present in groups B and C, but regression analysis
      revealed no relationship between F metabolites or the THF +/- 5alpha-THF/THE
      ratio and insulin action (homeostasis model assessment analysis and insulin
      values in the oral glucose tolerance test). There was, however, a highly
      significant relationship between the THF +/- 5alpha-THF/THE ratio and BMI (t = 
      3.44; P < 0.01) and total body fat (t = -2.27; P < 0.05). Stepwise regression
      analyses indicated an inverse relationship between THF+/-5alpha-THF/THE and
      scapular and waist fat (t = -2.25; P = 0.03) and a direct relationship with hip
      and thigh fat (t = 2.42; P = 0.02) in both sexes. The fall in the THF + 5alpha
      THF/THE ratio but unchanged UFF/UFE ratio together with impaired F concentrations
      after oral E indicates inhibition of 11betaHSD1 in subjects with obesity. This
      results in an increased MCR for F, explaining the increased F secretion rate in
      obesity in the face of normal circulating F concentrations. 11BetaHSD1 activity
      is highly related to body fat distribution, with android or central obesity, but
      not gynoid obesity, associated with reduced activity in both sexes. This
      reduction in 11betaHSD1 activity raises new questions as to the primary role of
      11betaHSD1 in the pathogenesis of insulin resistance and central obesity.

PMID- 10084591
TI  - Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin
      releasing hormone despite desensitization at fast pulse frequencies.
AB  - A pulsatile pattern of GnRH stimulation is essential for normal secretion of
      luteinizing hormone (LH), while both continuous and fast-frequency GnRH
      stimulation result in a paradoxical decrease in gonadotrope responsiveness known
      as desensitization. Under physiological conditions there is striking concordance
      between the pulsatile secretion of LH and the glycoprotein free alpha-subunit
      (FAS). The aims of this study were to determine whether the FAS response to GnRH
      is also decreased at fast frequencies of GnRH stimulation and whether FAS is
      superior to LH as a marker of GnRH secretory activity at fast-pulse frequencies.
      The model of GnRH-deficient men was chosen to permit precise control of the dose
      and frequency of GnRH stimulation of the gonadotrope. The frequency of i.v.
      administration of GnRH to 5 GnRH-deficient men was progressively increased from
      every 120 to every 60 min, from 60 to 30 min, and from 30 to 15 min during three
      12-h admissions, 1 week apart. The bolus dose of GnRH remained constant and was
      set at that dose previously shown to produce physiological concentrations and
      amplitudes of LH secretion and normal testosterone levels. As the frequency of
      GnRH stimulation was increased, a progressive rise in mean FAS levels was noted
      (353 +/- 13, 448 +/- 42, 466 +/- 50, and 698 +/- 85 ng/L [mean +/- SEM] for 120,
      60, 30, and 15 min intervals; P < 0.005). However, normalization of mean FAS
      levels to account for the increase in total GnRH delivered with increasing
      frequencies revealed a progressive decrease in pituitary responsiveness to each
      GnRH bolus with increasing frequency of stimulation (353 +/- 13, 224 +/- 21, 117
      +/- 13, 87 +/- 11 ng/L; P < 0.001). The decrease in normalized mean levels was
      supported by a decrease in the FAS pulse amplitude with increasing frequency (517
      +/- 53, 365 +/- 50, 176 +/- 29 ng/L for 120, 60, and 30 min intervals,
      respectively; P < 0.005). At interpulse intervals of 120 and 60 min, there was
      complete concordance of LH and FAS pulses in response to GnRH. However, at the 30
      min frequency FAS proved to be a better marker of GnRH with a higher true
      positive rate and lower number of false positives than LH (P < 0.05). At all
      frequencies, the number of false positive pulses detected tended to be lower for
      FAS than for LH (P = 0.06). From these data we conclude that FAS is subject to
      desensitization in response to increasing frequencies of GnRH administration in
      GnRH-deficient men, but is superior to LH as a surrogate marker of GnRH pulse
      generator activity at fast pulse frequencies.

PMID- 10084592
TI  - Counterregulatory response to hypoglycemia differs according to the insulin
      delivery route, but does not affect glucose production in normal humans.
AB  - The magnitude of the counterregulatory response to insulin-induced hypoglycemia
      is primarily determined by the degree of hypoglycemia. We examined whether the
      route of acute insulin delivery (portal or peripheral venous) is also important
      in determining the magnitude of the counterregulatory response to hypoglycemia in
      nine healthy nondiabetic men. Pancreatic insulin secretion, stimulated by an i.v.
      tolbutamide infusion (portal insulin study), was matched with an exogenous
      insulin infusion into the peripheral vein 4-6 weeks later (peripheral insulin
      study). Each study consisted of a 150-min baseline tracer equilibration period, a
      180-min euglycemic hyperinsulinemic (portal or peripheral insulin delivery)
      period, a 60-min hypoglycemic period in which insulin secretion diminished during
      tolbutamide or was reduced during exogenous insulin, and a 30-min recovery
      period. Peripheral venous glucose concentrations were well matched in the portal
      and peripheral studies during euglycemia and hypoglycemia (glucose nadir, 2.9 +/-
      0.1 mmol/L in the portal and 2.7 +/- 0.1 mmol/L in the peripheral; mean +/- SEM;
      P = NS), and insulin concentrations were about 1.5-fold higher throughout the
      experiment in the peripheral vs. the portal insulin study due to the first pass
      extraction of insulin in the portal study. There was a much greater increment (P
      < 0.0001) in FFA in the portal vs. the peripheral study (area under the curve:
      portal, 19.5 +/- 3.9 mmol/L x 90 min; peripheral, 3.3 +/- 1.1 mmol/L x 90 min),
      whereas plasma glucagon and GH were higher in the peripheral study (P = 0.01 for
      glucagon; P = 0.015 for GH). There was no significant difference between studies
      in epinephrine and norepinephrine responses to hypoglycemia or stimulation of
      endogenous glucose production (area under the curve: portal, 636 +/- 103
      micromol/kg x 90 min; peripheral, 705 +/- 69 micromol/kg x 90 min; P = NS). In
      summary, we have shown that the glucagon, GH, and FFA responses to hypoglycemia
      during insulin dissipation are affected by the route of insulin delivery and are
      not controlled exclusively by the nadir blood glucose level. The clinical
      importance of these observations in diabetic subjects as they relate to route of
      insulin delivery (portal or peripheral) during insulin dissipation remains to be
      determined.

PMID- 10084593
TI  - Locus heterogeneity of autosomal dominant osteopetrosis (ADO).
AB  - Autosomal dominant osteopetrosis (ADO), is a heritable disorder that results from
      a failure of osteoclast-mediated bone resorption. The etiology of the disorder is
      unknown. A previous linkage study of one Danish family mapped an ADO locus to
      chromosome 1p21. We have studied two families from Indiana with ADO. The present
      study sought to determine if the ADO gene in these families was also linked to
      chromosome 1p21. We used six microsatellite repeat markers, which demonstrated
      linkage to the 1p21 ADO locus in the Danish study, to perform linkage analysis in
      the new kindreds. Multipoint analysis excluded linkage of ADO to chromosome 1p21
      (logarithm of the odds score < -7.00) in both families. In addition, no haplotype
      segregated with the disorder in either family. In summary, the present
      investigation ruled out linkage of ADO to chromosome 1p21 in two families from
      Indiana. Our results demonstrate that there is locus heterogeneity of this
      disorder; therefore, mutations in at least two different genes can give rise to
      the ADO phenotype.

PMID- 10084594
TI  - Changes in bone turnover in young women consuming different levels of dietary
      protein.
AB  - Although high protein diets are known to increase urinary calcium excretion and
      induce negative calcium balance, the impact of dietary protein on bone turnover
      and fractures is controversial. We therefore evaluated the effect of dietary
      protein on markers of bone turnover in 16 healthy young women. The experiment
      consisted of 2 weeks of a well balanced diet containing moderate amounts of
      calcium, sodium, and protein followed by 4 days of an experimental diet
      containing one of three levels of protein (low, medium, or high). On day 4, serum
      and urinary calcium, serum PTH, 1,25-dihydroxyvitamin D, serum osteocalcin, bone
      specific alkaline phosphatase, and urinary N-telopeptide excretion were measured.
      Urinary calcium excretion was significantly higher on the high than on the low
      protein diet. Secondary hyperparathyroidism occurred on the low protein diet.
      Urinary N-telopeptide excretion was significantly greater during the high protein
      than during the low protein intake (48.2 +/- 7.2 vs. 32.7 +/- 5.3 nM bone
      collagen equivalents/mM creatinine; P < 0.05). There was no increase in
      osteocalcin or bone-specific alkaline phosphatase when comparing the low to the
      high diet, suggesting that bone resorption was increased without a compensatory
      increase in bone formation. Our data suggest that at high levels of dietary
      protein, at least a portion of the increase in urinary calcium reflects increased
      bone resorption.

PMID- 10084595
TI  - Human leukocyte antigen-DQB1* genotypes encoding aspartate at position 57 are
      associated with 3beta-hydroxysteroid dehydrogenase autoimmunity in premature
      ovarian failure.
AB  - Premature ovarian failure (POF) has an autoimmune pathogenesis in a significant
      proportion of cases. Autoantibodies to the steroid cell enzyme, 3beta
      hydroxysteroid dehydrogenase (3betaHSD) are present in one fifth of patients and
      may identify an autoimmune subgroup. As autoimmune diseases are associated with
      alleles of the human leukocyte antigen (HLA) genes, we examined the distribution
      of HLA-DRB1 and -DQB1 genotypes in 118 women with POF, of whom 21% had 3betaHSD
      autoantibodies, and 134 racially matched control subjects. Two HLA-DQB1 alleles,
      0301 and 0603, were associated with 3betaHSD autoantibody positivity (P = 0.04
      and P = 0.006, respectively). As the DQB1*0301 and -0603 genes share an identical
      codon at position 57 (aspartate, Asp), we analyzed the frequency of DQbeta-Asp57
      encoding DQB1 genes in our series. Eighteen of 21 POF patients with 3betaHSD
      autoantibodies had DQbeta-Asp57-encoding genotypes (haplotype frequency, 27 of
      42; 64%) compared with 92 of 134 control subjects (haplotype frequency, 109 of
      268; 41%; P = 0.004), and 9 of 21 (43%) cases were homozygous for codon 57
      genotypes compared with 17 of 134 (13%) control subjects (P = 0.0006). These
      probability values were not significant after correction for multiple testing,
      and these trends will therefore require confirmation in larger cohorts. HLA class
      II molecules present antigenic peptides to CD4+ T lymphocytes. DQbeta57 occupies
      a key site at the boundary of the peptide binding groove, with a major impact on
      peptide binding. Our preliminary demonstration of an association between POF,
      3betaHSD autoimmunity, and a distinctive HLA-DQ molecule supports the hypothesis
      that autoantibodies to this steroid cell enzyme may be markers of autoimmune
      ovarian failure and suggests that presentation of autoantigenic or external
      peptides to T lymphocytes by HLA-DQ molecules with Asp57-beta-chains is important
      in the pathogenesis of this disease.

PMID- 10084596
TI  - Two different mutations in the thyroid peroxidase gene of a large inbred Amish
      kindred: power and limits of homozygosity mapping.
AB  - Approximately 10% of newborns with congenital hypothyroidism are unable to
      convert iodide into organic iodine. This iodide organification defect has a
      prevalence of 1 in 40,000 newborns and may be caused by defects in the thyroid
      peroxidase enzyme (TPO), the hydrogen peroxide-generating system, the TPO
      substrate thyroglobulin, or inhibitors of TPO. We identified a high incidence of
      severe hypothyroidism due to a complete iodide organification defect in the
      youngest generation of five nuclear families belonging to an inbred Amish
      kindred. Genealogical records permitted us to trace their origin to an ancestral
      couple 7-8 generations back and to identify an autosomal recessive pattern of
      inheritance. Initial studies of homozygosity by descent using two polymorphic
      markers within the TPO gene showed no linkage to the phenotype. In fact, 4 of 15
      affected siblings from 2 of the nuclear families were heterozygous, resulting in
      homozygosity values of 73% and 53% in affected and unaffected family members,
      respectively. A genome-wide homozygosity screen using DNA pools from affected and
      unaffected family members localized the defect to a locus close to the TPO gene.
      Linkage analysis using 4 additional polymorphic markers within the TPO gene
      reduced the number of homozygous unaffected siblings to zero without altering the
      percent homozygosity initially found in the affected. Sequencing of the TPO gene
      revealed 2 missense mutations, E799K and R648Q. TPO 779K was found in both
      alleles of the 11 affected homozygotes, both mutations were present in each of
      the 3 affected compound heterozygotes, and there were no TPO mutations in 1
      subject with hypothyroidism of different etiology. These results demonstrate the
      power of the DNA pooling strategy in the localization of a defective gene and the
      pitfalls of linkage analysis when 2 relatively rare mutations coexist in an
      inbred population.

PMID- 10084597
TI  - Leptin antagonizes the insulin-like growth factor-I augmentation of
      steroidogenesis in granulosa and theca cells of the human ovary.
AB  - There is increasing evidence that leptin is a physiological link between obesity
      and infertility. Although leptin receptors have been demonstrated in human
      ovaries, there is no information regarding the effects of leptin on cells from
      developing ovarian follicles. To test the direct effects of leptin on human
      ovarian cells, granulosa cells (GC) and theca cells were isolated from the
      ovaries of regularly cycling women. Serum was obtained at the time of surgery,
      and follicular fluid was aspirated from the follicles before isolation of the
      ovarian cells. Leptin concentrations were similar in follicular fluid and serum.
      RT-PCR analysis demonstrated that the long, signaling form of the leptin receptor
      was expressed in both theca and GC. In cultured GC, leptin had no effect on
      estradiol production, alone or in the presence of FSH, but caused a concentration
      related inhibition of the insulin-like growth factor I (IGF-I) augmentation of
      FSH-stimulated estradiol production. The effect of leptin was specific, because
      there was no effect on progesterone production. In cultured theca cells, leptin
      did not alter androstenedione production, alone or in the presence of LH. Leptin
      caused a concentration-related inhibition of the IGF-I augmentation of LH
      stimulated androstenedione production. These data demonstrate that leptin can
      directly inhibit IGF-I action in ovarian theca and GC at concentrations commonly
      present in obese women.

PMID- 10084598
TI  - The hepatic nuclear factor-1alpha G319S variant is associated with early-onset
      type 2 diabetes in Canadian Oji-Cree.
AB  - Mutations in the gene encoding hepatic nuclear factor-1alpha (HNF-1alpha) have
      been found in patients with maturity-onset diabetes of the young. We identified a
      new variant in the HNF-1alpha gene, namely G319S, in Ontario Oji-Cree with type 2
      diabetes. G319S is within the proline II-rich domain of the trans-activation site
      of HNF-1alpha and alters a glycine residue that is conserved throughout
      evolution. S319 was absent from 990 alleles taken from subjects representing six
      other ethnic groups, suggesting that it is private for Oji-Cree. We found that 1)
      the S319 allele was significantly more prevalent in diabetic than nondiabetic Oji
      Cree (0.209 vs. 0.087; P = 0.000001); 2) S319/S319 homozygotes and S319/G319
      heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95%
      confidence interval, 2.65-6.03) and 1.97 (95% confidence interval, 1.44-2.70)
      compared with G319/G319 homozygotes; 3) there was a significant difference in the
      mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319
      subjects affected in the fifth, fourth, and third decades of life, respectively.
      In subjects with type 2 diabetes, we also found significantly lower body mass
      index and significantly higher post-challenge plasma glucose in S319/S319 and
      S319/G319 compared with G319/G319 subjects. Finally, among nondiabetic subjects,
      S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319
      homozygotes. The presence of the private HNF-1alpha G319S variant in a large
      number of Oji-Cree with type 2 diabetes and its strong association with type 2
      diabetes susceptibility are unique among human populations. Also, G319S is
      associated with a distinct form of type 2 diabetes, characterized by onset at an
      earlier age, lower body mass, and a higher postchallenge plasma glucose.

PMID- 10084599
TI  - Mechanisms subserving the physiological nocturnal relative hypoprolactinemia of
      healthy older men: dual decline in prolactin secretory burst mass and basal
      release with preservation of pulse duration, frequency, and interpulse interval-
      a General Clinical Research Center study.
AB  - Increasing age is accompanied by decrements in randomly obtained, fasting, or
      frequently sampled serum PRL concentrations. The precise neuroendocrine
      mechanisms underlying such relative hypoprolactinemia in aging are incompletely
      understood. In the present study, we sampled blood at 2.5-min intervals overnight
      in 11 young (aged 21-34 yr) and 8 older (aged 62-72 yr) healthy men for
      subsequent chemiluminescence-based assay of serum PRL concentrations. The mean
      (+/- SEM) serum PRL concentration was significantly reduced at 4.3 +/- 0.78
      microg/L in older men compared with 9.5 +/- 1.2 microg/L in young volunteers (P =
      0.0049). PRL concentrations correlated with serum testosterone (r = 0.473; P =
      0.041), dehydroepiandrosteroen sulfate (r = +0.455, P = 0.05), and insulin-like
      growth factor I (r = 0.494; P = 0.032) levels. Deconvolution analysis was used to
      evaluate combined pulsatile and basal modes of PRL secretion. In older men,
      discrete PRL secretory bursts were marked by a significantly (2.4-fold)
      attenuated mass of hormone secreted per burst (amount of PRL secreted per unit
      distribution volume), viz. 1.6 +/- 0.23 (older) vs. 3.9 +/- 0.57 microg/L (young;
      P < 0.01). In contrast, PRL secretory burst frequency, interpulse interval, and
      pulse duration were invariant of age. Concomitantly, basal PRL secretion was
      reduced by 2-fold in older subjects, namely to 0.00030 +/- 0.00027 (older) vs.
      0.00065 +/- 0.0002 microg/L/min (young; P < 0.01). The amount of total PRL
      secretion that was pulsatile averaged 82 +/- 5.3% in young and 99 +/- 0.13% in
      older men (P = 0.012), indicating preferential loss of the basal mode of PRL
      release in aging. Assuming that basal PRL secretion mirrors functional pituitary
      lactotroph cell secretory mass, whereas pulsatile PRL release reflects effective
      (net) intermittent hypothalamic drive to responsive lactotroph cells, then our
      results suggest both an attrition in lactotroph cell mass and an impoverishment
      of net positive hypothalamic (agonistic) input to lactotrophs in older men. Given
      the multiple roles of PRL reported in experimental animals (e.g. on the one hand
      to support immune function and adrenal androgen biosynthesis and on the other
      hand to activate intraprostatic growth factors), we suggest that the nocturnal
      relative hypoprolactinemia observed in healthy aging men may have both adaptive
      and maladaptive clinical implications to target tissues.

PMID- 10084600
TI  - Androgen receptor-mediated hypersensitivity to androgens in women with
      nonhyperandrogenic hirsutism: skewing of X-chromosome inactivation.
AB  - Idiopathic hirsutism may result from an increase in the androgen receptor (AR)
      mediated sensitivity of the hair follicle. The AR gene is located on the X
      chromosome and contains a highly polymorphic trinucleotide repeat (CAGn) in its
      first exon, whose length and methylation pattern affect both AR expression and
      function. We analyzed these CAG repeats in the genomic DNA from 16
      nonhyperandrogenic hirsute patients (Ferriman score: 16 +/- 4.7, mean +/- SD) and
      10 normal controls (Ferriman score: 3 +/- 1.4), who were similar in their
      hormonal profiles. We found no difference in the number of CAG repeats between
      hirsute patients and controls, and no correlation between number of repeats and
      the Ferriman score or hormonal values. However, after DNA digestion with
      methylation-sensitive HpaII and measurement of the optical density, we found a
      marked decrease in the hirsute group (P < 0.0001), which was greater than in the
      control group (P = 0.0003). In addition, in the hirsute patients, the shorter of
      the two alleles was preferentially less methylated (P = 0.007), suggesting
      skewing of X-chromosome inactivation in the patients but not in the controls.
      When the mean optical density of both alleles was correlated with the Ferriman
      score, we observed a significant negative correlation (P = 0.02, r = -0.45),
      which became stronger when the shorter alleles were analyzed separately (P =
      0.01; r = 0.48). We conclude that nonhyperandrogenic hirsutism is associated with
      skewing of X-chromosome inactivation in peripheral blood lymphocytes. This leads
      to the longer of the two AR alleles being preferentially methylated, allowing for
      the shorter (and presumably, more functional) allele to be expressed on the
      active X-chromosome. Further studies need to be performed to investigate whether
      this phenomenon is present in androgen-sensitive tissues in these patients.

PMID- 10084601
TI  - Binding properties and distribution of insulin-like growth factor binding protein
      related protein 3 (IGFBP-rP3/NovH), an additional member of the IGFBP
      Superfamily.
AB  - The protein product of the novH oncogene, a member of the CCN family, is
      structurally related to the insulin-like growth factor (IGF) binding proteins
      (IGFBPs). We have characterized aspects of structure, function, and distribution
      of this protein, which, as IGFBP-related protein 3 (IGFBP-rP3), is a proposed
      member of the IGFBP Superfamily. Affinity cross-linking experiments performed
      with baculovirus synthesized recombinant human IGFBP-rP3 established that rhIGFBP
      rP3 binds IGF-I, IGF-II, and insulin with low affinity. Specificity of binding
      was shown by competitive cross-linking experiments; binding to IGF-I and -II was
      also demonstrated by nondenaturing Western ligand blots. Northern blot analysis
      indicated the presence of IGFBP-rP3 messenger RNA (mRNA) in a broad range of
      human tissues. Western immunoblotting studies, using a polyclonal rabbit anti
      rhIGFBP-rP3 antibody, demonstrated that IGFBP-rP3 protein is synthesized in vitro
      by several breast and prostate cancer cell lines: Hs578T, PC3, P69, and LNCaP
      cells. Western immunoblotting studies of human biological fluids identified that
      IGFBP-rP3 was present in normal serum, pregnancy serum, serum from patients with
      growth hormone receptor deficiency, cerebrospinal fluid, amniotic fluid,
      peritoneal fluid, and follicular fluid, while IGFBP-rP3 fragments were identified
      in cerebrospinal fluid, amniotic fluid, and prepubertal and pubertal urine
      samples. Our studies demonstrate that IGFBP-rP3 exhibits IGF binding, albeit at
      low affinity, and IGFBP-rP3 thus merits inclusion in the IGFBP Superfamily. The
      low affinity IGF binding suggests that IGFBP-rP3 may act primarily independently
      of the IGFs. The synthesis of IGFBP-rP3 by several malignant cell lines and its
      presence in human biological fluids suggest that this protein possesses other
      interesting roles, potentially in cell growth regulation.

PMID- 10084602
TI  - Regulation of CD97 protein in thyroid carcinoma.
AB  - CD97 is a dimeric glycoprotein belonging to the secretin receptor superfamily and
      is abundantly expressed in cells of hematopoietic origin. The aim of this study
      was to analyze the expression of the CD97 protein in thyroid carcinomas and the
      role of all-trans-retinoic acid (RA) in the regulation of CD97 protein in
      monolayer culture of the human follicular thyroid carcinoma cell line FTC-133. In
      normal thyroid tissue, no immunoreactivity of CD97 could be found, whereas in
      differentiated thyroid carcinomas, CD97 expression was either lacking or low.
      Undifferentiated anaplastic thyroid carcinomas revealed high CD97 expression. The
      expression of CD97 protein seems to be correlated to the postoperative
      histopathological classification staging. Approximately 50% of FTC-133 cells
      expressed the CD97 protein under basal culture conditions. No differences were
      found in the number of CD97-positive cells after TSH, forskolin, and insulin
      treatment compared to control values. Epidermal growth factor treatment led to an
      increase in CD97 immunostaining (up to 90%), whereas phorbol 12-myristate 13
      acetate slightly decreased the immunoreactivity of CD97 (from 50% to 30%). Under
      basal conditions, RA treatment for 72 h led to a decrease in total cell number by
      33% and in CD97-positive cells from 50% to 30%. TSH, forskolin, phorbol 12
      myristate 13-acetate, and insulin showed no effect after 72-h pretreatment with
      RA, whereas epidermal growth factor treatment led to a slight increase in the
      number of the CD97-positive cells (from 30% to 40%) compared to the control
      value. These data suggest that CD97 expression may play an important role in the
      dedifferentiation of thyroid tumors, and RA might interfere with this process in
      thyroid carcinoma by suppressing the dedifferentiation marker CD97.

PMID- 10084603
TI  - Proliferation and apoptosis in the human adrenal cortex during the fetal and
      perinatal periods: implications for growth and remodeling.
AB  - After 10-15 weeks of gestation, the human fetal adrenal cortex undergoes rapid
      growth due to enlargement of a specialized cortical compartment known as the
      fetal zone (FZ). Soon after birth, the FZ regresses and the adult zonation
      pattern develops at least in part from cells derived from the persistent
      definitive zone (DZ), a thin layer of tightly packed cells surrounding the FZ. We
      postulated that growth of the fetal adrenal cortex involves zone-specific
      cellular hyperplasia, whereas the postnatal involution of the FZ is due to
      apoptosis. Therefore, we investigated the pattern of cellular proliferation and
      death in the FZ and DZ of the human fetal and postnatal adrenal cortex using
      immunohistochemical staining for proliferating cell nuclear antigen as a marker
      of mitosis and in situ detection of DNA fragmentation as a marker of apoptosis.
      Between 10-14 weeks' gestation, the mitotic indexes (percentage of proliferating
      cell nuclear antigen-positive cells) in the DZ (26.46 +/- 2.95%) and in the FZ
      (21.26 +/- 2.57%) were not significantly different. Between 15-20 weeks
      gestation, the mitotic index increased significantly (P < 0.05) in both zones
      (FZ, 33.84 +/- 5.21%; DZ, 67.45 +/- 7.58%) relative to levels before 15 weeks.
      This increase persisted between 21-24 weeks gestation (FZ, 39.5 +/- 4.22%; DZ,
      58.63 +/- 6.83%). Interestingly, after 14 weeks, the mitotic index of the DZ was
      significantly greater (P < 0.05) than that of the FZ. In adrenal specimens
      obtained from infants born prematurely and treated in utero with glucocorticoid,
      the mitotic indexes in the FZ and DZ were significantly decreased. At all stages
      of gestation, no apoptotic nuclei were detected in the DZ. However, scattered
      apoptotic nuclei were detected in the central portions of the FZ. The number of
      apoptotic nuclei in the inner FZ increased with advancing gestation and was
      maximal during the first postnatal month. To identify factors that may regulate
      apoptosis, primary cultures of midgestation FZ cells were treated with activin A
      and transforming growth factor-beta (TGFbeta). Activin A and TGFbeta both induced
      apoptotic cell death, as assessed by internucleosomal DNA cleavage (DNA
      laddering). Induction of apoptosis by activin A was prevented by concomitant
      addition of follistatin, an activin-binding protein. Taken together, these data
      indicate that 1) growth of the human fetal adrenal cortex involves cellular
      hyperplasia, mainly in the DZ and to a lesser extent in the FZ, which is probably
      dependent on ACTH; and 2) apoptosis occurs predominantly in the inner cortical
      compartment and may be responsible for the rapid regression of the FZ after
      birth, a process that may be regulated by activin A and/or TGFbeta.

PMID- 10084604
TI  - Comparative genomic hybridization analysis of adrenocortical tumors of childhood.
AB  - Although several genes have been investigated in adrenal tumorigenesis, the
      genetic background of adrenocortical tumors (ACT) remains poorly characterized.
      In southern Brazil, the annual incidence of ACT is unusually high, ranging from
      3.4-4.2/million children, compared with a worldwide incidence of 0.3/million
      children younger than 15 yr. Environmental factors have been implicated because
      the distribution of these tumors follows a regional, rather than a familial,
      pattern. However, decreased penetrance of a particular gene defect cannot be
      excluded. Because linkage or other traditional genetic analyses would not be
      appropriate to investigate the defect(s) associated with ACT in this population,
      we used comparative genomic hybridization (CGH) to screen for DNA sequence copy
      number changes in 9 nonfamilial ACT (6 carcinomas and 3 adenomas) from unrelated
      patients from this region. Six female (aged 10 months to 6 3/4 yr) and 3 male (1
      1/12 to 3 1/4 yr) patients were studied. Three carcinomas were at stage I, 1 was
      at stage II, and another was at stage III. Two carcinomas had evidence of
      invasion of the vena cava, and 3 were more than 3 cm in size. All patients
      underwent surgical excision of their tumors; chemotherapy was administered to
      cancer patients. Currently, all patients are alive and in remission, with the
      exception of 1 patient with stage III cancer. High mol wt DNA was extracted from
      tumor tissue obtained at surgery and frozen at -70 C. This DNA was labeled and
      used for CGH according to standard procedures. Digital image analysis was
      performed to detect chromosomal gains or losses. CGH evaluation revealed
      extensive genetic aberrations in both adenomas and carcinomas; there were no
      significant differences relative to age, gender, size, or stage of the tumor (P >
      0.1). Chromosomes and chromosomal regions 1q, 5p, 5q, 6p, 6q, 8p, 8q, 9q, 10p,
      11q, 12q, 13q, 14q, 15q, 16, 18q, 19, and 20q demonstrated gains, whereas 2q, 3,
      4, 9p, 11, 13q, 18, 20p, and Xq showed losses. The most striking finding was
      consistent copy number gain of chromosomal region 9q34 in 8 of the 9 tumors. We
      conclude that both benign and malignant ACT from southern Brazil show multiple
      genetic aberrations, including a consistent gain of chromosomal region 9q34. This
      genomic area may harbor genetic defects that predispose to ACT formation and are
      shared by the patients who were investigated in this study or are accumulated
      epigenetically under the influence of a common factor, such as an environmental
      mutagen.

PMID- 10084605
TI  - Synaptophysin immunoreactivity in primary pigmented nodular adrenocortical
      disease: neuroendocrine properties of tumors associated with Carney complex.
AB  - Carney complex (CNC) is characterized by lentiginosis and myxomatosis together
      with a variety of endocrine, neural crest-derived, and other tumors, including
      primary pigmented nodular adrenocortical disease (PPNAD). PPNAD is characterized
      by lipofuscin-containing, autonomously functioning, cortisol-producing nodules
      surrounded by mostly atrophic adrenocortical and normal adrenomedullary tissue.
      The nature and origin of the tumors, including the myxomas and PPNAD, are
      unclear. In this study, seven paraffin-embedded PPNAD tumors, one skin myxoma,
      and two cell lines (one myxoma and one PPNAD) established from patients with CNC
      were stained with antisera for synaptophysin (SYN), neuron-specific enolase,
      chromogranin A, tyrosine hydroxylase, and the neural cell adhesion molecule
      (NCAM). In addition, one PPNAD specimen and one myxoma were analyzed by electron
      microscopy. The results showed that chromogranin A and tyrosine hydroxylase
      stained adrenomedullary tissue, but not the PPNAD nodules or the extranodular
      adrenal cortex. SYN, neuron-specific enolase, and NCAM also stained the medulla.
      PPNAD nodules and the PPNAD cell line, but not the extranodular adrenal cortex,
      stained intensely for SYN. The myxoma cell line, but not normal fibroblasts,
      stained for SYN and NCAM. Ultrastructural analysis of a PPNAD tumor and a skin
      myxoma revealed a well developed rough endoplasmic reticulum, prominent
      mitochondria, and vesicle-like structures dispersed throughout the cytoplasm. We
      conclude that immunostaining for SYN, a marker protein for neuroendocrine cells,
      clearly distinguishes PPNAD nodules from surrounding adrenocortical tissue and
      can be helpful in the detection of small nodules in apparently unaffected cortex.
      The cells of a cutaneous myxoma were also stained positive by two of the three
      neuroendocrine markers. Finally, both PPNAD and myxoma cells demonstrated
      ultrastructural features suggestive of neuroendocrine properties. These results
      support the previously suggested hypothesis that the genetic mechanism leading to
      CNC involves genes with a neuroendocrine role.

PMID- 10084606
TI  - Sex steroids mediate HOXA11 expression in the human peri-implantation
      endometrium.
AB  - Under the influence of sex steroids, human endometrium undergoes sequential
      development in preparation for implantation. Hoxa11 is essential for implantation
      in the mouse. Here we describe a potential role for HOXA11 in human endometrial
      development and implantation. Northern analysis demonstrates that HOXA11 is
      expressed in a menstrual cycle phase-dependent fashion in adult human
      endometrium. HOXA11 messenger RNA levels dramatically increase at the time of
      implantation and remain increased in pregnancy. In vitro, HOXA11 expression is
      increased in response to estrogen or progesterone. There is a dose-responsive
      increase over the physiologic range of progesterone concentration. Pretreatment
      with Cyclohexamide does not decrease the response to estrogen. Steroids are novel
      regulators HOX gene expression. The spatial and temporal pattern of HOXA11
      expression in the human endometrium suggests a role in endometrial development,
      implantation, and maintenance of pregnancy.

PMID- 10084607
TI  - A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene
      in familial and sporadic patients with male LH-independent precocious puberty.
AB  - Herein, we report mutation analysis of the LH receptor gene in 17 males with LH
      independent precocious puberty, of which 8 were familial and 9 had a negative
      family history. A total of 7 different mutations (all previously reported) were
      detected in 12 patients. Among 10 European familial male-limited precocious
      puberty (FMPP) patients who had a LH receptor gene mutation, none had the
      Asp578Gly mutation, which is responsible for the vast majority of cases in the
      U.S. The restricted number of activating mutations of the LH receptor observed in
      this and other studies of FMPP strongly suggests that an activating phenotype is
      associated with very specific sites in the receptor protein. Clinical follow-up
      of the 5 patients who did not have LH receptor mutations shows that such cases
      most likely do not have true FMPP. LH receptor mutation analysis provides a
      sensitive tool for distinguishing true FMPP from other causes of early-onset LH
      independent puberty in males.

PMID- 10084608
TI  - Increase in plasma interleukin-10 following hydrocortisone injection.
AB  - In view of the fact that glucocorticoids have an immunosuppressive effect and the
      fact that interleukin-10 (IL-10) is inhibitory to T helper cell function, we have
      now investigated the effect of hydrocortisone on plasma IL-10 concentrations.
      Seven normal subjects were injected with 100 mg hydrocortisone intravenously
      between 8 and 9:00 a.m. Sequential blood samples were obtained prior to and 1, 2,
      4, 8 and 24 h after the injection. Plasma IL-10 concentrations increased
      significantly and consistently following the injection in all subjects. The peak
      increase of IL-10 occurred at 4 h and the restoration to baseline by 8 h. The
      sequential values were (mean+/-SD): 3.0+/-1.3 pg/ml at 2 h, 9+/-4.2 pg/ml at 4 h,
      3.7+/-1.8 pg/ml at 8 h and 3.7+/-1.4 pg/ml at 24 h. The magnitude of increase was
      436% of the basal at peak effect. This effect of hydrocortisone (and possibly
      other glucocorticoids) may contribute to the immunosuppressive effect of this
      drug. IL-10 may also be potentially useful in the assessment of Cushing's
      Syndrome as a marker of end organ effect of glucocorticoids.

PMID- 10084609
TI  - Cord blood leptin is associated with size at birth and predicts infancy weight
      gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and
      Childhood.
AB  - Recent discoveries of human genetic leptin deficiency have demonstrated its
      importance in regulating weight gain in early childhood. To investigate whether
      normal variation in leptin and insulin levels in cord blood could influence
      infancy growth, we assayed samples from 197 infants from a representative birth
      cohort, who were measured at birth, 4, 8, 12 and 24 months. Cord leptin levels
      correlated most closely with weight and ponderal index (kg/m3) at birth, but also
      with length and head circumference (all p<0.0005). Independent of birth size,
      females had higher leptin levels than males (p<0.0005). Cord levels of leptin,
      but not insulin, were negatively related to weight gain (p<0.005) from birth to 4
      months, and accounted for 9.4% of the variance in weight gain, compared with
      breast/bottle feeding (3.5%) and early/late introduction of solids (1%). The
      effect of leptin levels on weight gain was independent of birthweight, and was
      still evident at 24 months. The wide variation in infancy growth ('catch-up' or
      'catch-down') may be partly determined by leptin levels preset in utero. Our data
      support a role for leptin in the regulation of infancy weight gain, and suggest a
      mechanism whereby infants may 'catch-up' in growth postnatally following an
      adverse intrauterine environment.

PMID- 10084610
TI  - An intronless homolog of human proto-oncogene hPTTG is expressed in pituitary
      tumors: evidence for hPTTG family.
AB  - A novel proto-oncogene, PTTG (Pituitary Tumor Transforming Gene), was isolated in
      our laboratory by virtue of its increased expression in rat pituitary tumor cell
      lines. Cells which overexpress human or rat PTTG form tumors in athymic mice.
      hPTTG is highly expressed in cancer cell lines, pituitary adenomas and in normal
      testis, suggesting that hPTTG protein has different tissue-specific interactions
      in normal cells and in cancer. Alternatively, different hPTTG gene family members
      may be functional in normal development and in tumorigenesis. While mapping the
      chromosomal location of hPTTG to 5q33, we discovered a second gene, hPTTG2, which
      is intronless and maps to chromosome 4p12. Using gene-specific oligonucleotide
      hybridization in a PCR-ELISA assay, we determined that hPTTG2 is expressed in
      both normal and tumorous pituitary. However, high levels of hPTTG mRNA in cancer
      cell lines are due to increased expression of hPTTG1. Thus, this family of proto
      oncogenes appears to differentially participate in tumor-specific pathogenesis.

PMID- 10084611
TI  - The human prolactin receptor gene structure and alternative promoter utilization:
      the generic promoter hPIII and a novel human promoter hP(N).
AB  - The 5'-untranslated region of the human prolactin receptor (hPRLR) gene contains
      two alternative first exons, hE1(3), the human counterpart of the rat and mouse
      E1(3) and a novel human type of alternative first exon termed hE1N, also a common
      non-coding exon 2 and a third exon containing the translation initiation codon.
      hE1(3) was localized approximately 800 bp 5' from the hE1N in the genome. The two
      distinct first exons hE1(3) and hE1N are expressed in human breast tissue, breast
      cancer cells, gonads and liver. Overall, the transcript containing hE1(3) is
      prevalent in most tissues. The coding region of the gene comprises eight exons
      (exon 3-10), in which exon 10 encodes most of the intracellular domain. hE1(3)
      and hE1N are transcribed from alternative promoters hPIII and hP(N),
      respectively. The hPIII, containing identical Sp1 and C/EBP elements as in the
      rodent promoters, shares 81% similarity in the region -480/-106 to both the rat
      and mouse. The novel promoter hP(N) contains putative binding sites for ETS
      family proteins and a half-site for nuclear receptors. Therefore, both promoters
      likely utilize distinct mechanisms in controlling the hPRLR gene transcription.
      The different promoter utilization of the hPRLR gene in diverse tissues may
      confer differential prolactin response through activation of different promoters.

PMID- 10084612
TI  - Equine type estrogens produced by a pregnant woman carrying a Smith-Lemli-Opitz
      syndrome fetus.
AB  - The equine-type estriols 1,3,5(10),7-estratetraene-3,16alpha,17beta-triol
      (16alpha-hydroxy-17beta-dihydroequilin) and 1,3,5(10),6,8-estrapentaene
      3,16alpha,17beta-triol (16alpha-hydroxy-17beta-dihydroequilenin) constituted over
      half of the estrogens excreted by a woman carrying a Smith-Lemli-Opitz syndrome
      (SLOS) affected fetus. The steroids were characterized by gas chromatography-mass
      spectrometry (GC/MS), and mass spectra of the dehydro estriols as trimethylsilyl
      ethers are illustrated. SLOS is associated with 7-dehydrocholesterol (7DHC),
      delta 7-reductase deficiency; the enzyme catalyzing the final step in cholesterol
      biosynthesis. Identification of these equine estrogens show that an estrogen
      biosynthetic pathway parallel to normal is functional in the feto-placental unit
      and uses 7DHC as precursor, therefore P450scc, P450c17, and 3betaHSD and P450arom
      are all active on 7-dehydrometabolites. Patients with affected fetuses have low
      plasma estriol values (probably due to deficient production of the cholesterol
      precursor) and this is often a warning sign which instigates further evaluation
      for SLOS. The estriol deficiency is not quantitatively made up by the
      dehydrometabolites, and the combined excretion was found to be about one-third of
      the mean of gestational age matched controls. The importance of these findings
      lies in the potential value of dehydroestriol measurement for non-invasive
      diagnosis of SLOS at mid-gestation. Currently diagnosis relies on imaging, since
      SLOS is a malformation syndrome, and measurement of 7DHC levels in amniotic fluid
      and chorionic villus tissue.

PMID- 10084613
TI  - A longitudinal study of lifestyle factors as predictors of injuries and crashes
      among young adults.
AB  - This study was part of the Dunedin Multidisciplinary Health and Development
      Study. This is a longitudinal study of the health, development and behaviour of a
      cohort of 1037 young people born in Dunedin, New Zealand between 1 April 1972 and
      31 March 1973. Explanatory measures covering background, behavioural and
      personality factors were obtained at ages 15 and 18 and were used as potential
      predictors of outcomes reported at age 21. Four outcomes were considered: any
      crash, injury crash, non-injury crash, and serious injury (not motor vehicle
      related). Overall, very few lifestyle factors were important predictors of any of
      these outcomes. Factors that were shown to predict injury crashes differed from
      those that predicted non-injury crashes. Also, those that predicted a traffic
      crash differed from those that predicted a serious non-traffic injury. These
      results suggest that focusing injury prevention efforts on changing the
      lifestyles of young adults is unlikely to reduce overall crash risk, and would
      have little impact on the risk of serious injury.

PMID- 10084614
TI  - Bicycle injuries in Western Sweden: a comparison between counties.
AB  - The objectives of the study were to investigate whether there are differences in
      the incidence of bicycle-related injuries by geographic district (county), age,
      and gender in Sweden's Western Road Administration Region, and to utilize any
      detected differences to suggest priorities for intervention and prevention.
      Injury data come from the Swedish national hospital-discharge registry and a
      specialized national register of occupational injuries. Both bodily injuries in
      general and head injuries in particular show intra-regional differences. The
      rural part of Skaraborg County was shown to have a significantly higher injury
      incidence than other parts of the Western Region. Females generally show a lower
      incidence than males, but older women are more likely to be seriously injured
      than younger (age-related differences being greater than for males). Some
      striking findings were found with regard to occupational differences. Females
      sustain more work-related bicycle injuries than males. Head injuries account for
      more than half of the bicycle injuries in the Western Region that require
      hospitalization. All this indicates that targeted measures are required. Some
      studies have shown that the use of bicycle helmets reduces the incidence of head
      injuries, the degree of their severity, and the number of bicycle-related
      fatalities. There is a need for mandatory helmet-wearing legislation, which must
      go hand-in-hand with special efforts to reach groups with a low rate of helmet
      wearing, in particular those in the middle age range. Although the grown-up/older
      cycling population has been the subject of targeted action in some countries, the
      focus of preventive activity has generally been on children. The results of the
      study suggest the need for further injury-related research into adult cycling.

PMID- 10084615
TI  - Impact conditions in side-impact collisions with fixed roadside objects.
AB  - Designing vehicles and roadside structures that are safer in side-impact
      collisions is an emerging area of concern in roadside safety research. Selecting
      impact conditions that are relevant to the way side-impact collisions occur in
      real world collisions is an important part of developing effective full-scale
      crash test procedures and evaluation criteria. If test impact conditions are
      unrealistically severe, improving the performance of roadside hardware for side
      impacts may appear unfeasible. If test impact conditions are not demanding
      enough, good performance in full-scale crash tests may not be indicative of good
      performance in real-world crashes. The purpose of this paper is to examine the
      best available accident data to determine what the reasonable worst case test
      impact conditions are for side-impacts with roadside objects.

PMID- 10084616
TI  - Junction road accidents during cross-flow turns: a sequence analysis of police
      case files.
AB  - In-depth studies of behavioural factors in road accidents using conventional
      methods are often inconclusive and costly. In a series of studies exploring
      alternative approaches, 200 cross-flow junction road accidents were sampled from
      the files of Nottinghamshire Constabulary, UK, coded for computer analysis using
      a specially devised Traffic Related Action Analysis Language, and then examined
      using different computational and statistical techniques. For comparison, the
      same analyses were carried out on 100 descriptions of safe turns, and 100
      descriptions of hypothetical accidents provided by experienced drivers. The
      present study employed a range of sequence analysis techniques to examine the
      patterns of events preceding accidents of different types. Differences were found
      between real accidents, hypothetical ones and safe turns; between accidents
      turning onto and off a road with the right of way; between the accidents of
      younger and older drivers; between accidents on minor roads and major roads; and
      between the accident expectations (but not the real accidents) of male and female
      drivers. Pairs of successive events often provided particularly good cues for
      discriminating accident types.

PMID- 10084617
TI  - An evaluation of the specific deterrent effects of vehicle impoundment on
      suspended, revoked, and unlicensed drivers in California.
AB  - There have been a number of studies conducted during the past two decades that
      convincingly demonstrate that license suspension and revocation are some of the
      most effective countermeasures currently available for attenuating the traffic
      safety risk of problem drivers. At the same time, it is also known that most
      suspended/revoked (S/R) drivers violate their illegal driving status and continue
      to drive, accruing traffic convictions and becoming involved in crashes. In an
      attempt to strengthen license actions and to better control S/R and unlicensed
      drivers, California enacted two laws effective January 1995 which provide for the
      impoundment and forfeiture of vehicles driven by S/R and unlicensed drivers. The
      study described in this paper evaluates the impact of vehicle impoundment on the
      1-year subsequent driving behavior of S/R and unlicensed drivers who experience
      this sanction. The results show that drivers with no prior convictions for
      driving while S/R or unlicensed whose vehicles were impounded have, relative to
      similar drivers whose vehicles were not impounded: 23.8% fewer driving while
      suspended/revoked or unlicensed convictions; 18.1% fewer traffic convictions; and
      24.7% fewer crashes. The differences between the impound and no-impound groups
      are even larger when the driving records of repeat offenders (i.e. drivers with
      prior driving-while-S/R or unlicensed convictions) are examined. Repeat offenders
      whose vehicles are impounded have 34.2% fewer driving-while-S/R or unlicensed
      convictions, 22.3% fewer traffic convictions and 37.6% fewer crashes. These
      findings provide strong support for impounding vehicles driven by S/R and
      unlicensed drivers.

PMID- 10084618
TI  - Traffic fatalities, Peltzman's model, and directed graphs.
AB  - We show how statistical methods based on directed graphs may be useful in
      modeling traffic fatalities by comparing models specified using directed graphs
      to a model originally developed by Peltzman. The comparison uses Peltzman's
      original data, as well as up-dated data (and coefficients) through 1993. Out-of
      sample forecasts of traffic fatalities from Peltzman's model are compared with
      those from a model constructed using directed graphs over data for the more
      recent period. The directed graphs model outperforms Peltzman's model in root
      mean squared forecast error.

PMID- 10084619
TI  - Seatbelt use and belief in destiny among Hispanic and non-Hispanic drivers.
AB  - In order to determine if fatalism is associated with seatbelt use, 312 drivers
      were recruited from convenience stores located within 12 randomly generated zip
      code areas along the Texas-Mexico border. The seatbelt use of drivers was
      recorded unobtrusively; self-reported seatbelt use and belief in destiny
      (fatalism) were subsequently obtained by interview. The majority of respondents
      rejected a fatalistic orientation, although Hispanic drivers were significantly
      less likely to do so. Fatalism was not associated with observed seatbelt use. Our
      results suggest that ethnic differences in seatbelt use are not due to ethnic
      differences in fatalism. These findings have implications for developing health
      interventions in Hispanic and non-Hispanic communities.

PMID- 10084620
TI  - Differences between pickup truck and automobile driver-owners.
AB  - This study compares pickup truck driver-owners and drivers who owned only
      automobiles with respect to demographic factors, conditions of use, risk-taking
      driving behavior, prior driving history and attitudes towards motor vehicle laws.
      A telephone survey conducted in Riverside County, CA determined that 36% of the
      households had a pickup truck. Pickup truck owners were primarily male, aged 30
      39 years, married, reported lower restraint use and more risky driving behaviors,
      and had more traffic citations. Differences in behaviors and attitudes were
      largely a function of age and gender. There is a need to design appropriate
      occupant safety interventions for those most likely to own pickup trucks.

PMID- 10084621
TI  - In-vehicle videotaping of drinking driver traffic stops in Oregon.
AB  - The purpose of this evaluation is to examine effectiveness of the use of video
      cassette recorders during traffic stops for drunk driving. This is accomplished
      by comparing traffic stops that employed video cassette recorders with traffic
      stops that did not, based on 1341 arrests taken from logs kept by state, city and
      county enforcement agencies from January 1994 through October 1995. Of the 1341
      arrests, 330 used videotaping. Three measures were examined, successful
      prosecution rate, time until disposition and implied consent hearing requests. If
      the arrest is videotaped a higher proportion resulted in diversion and about the
      same proportion resulted in convictions. Fewer were still pending or resolved in
      the defendant's favor. Also, videotaping appears to shorten the time until case
      disposition. Finally, the probability that an implied consent hearing will be
      requested and/or held is clearly higher if the arrest is videotaped. Based on
      these findings, it was concluded that in-vehicle videotaping of drunk driving
      arrests is effective to the extent that it leads to more arrests being resolved
      in the state's favor. However, the evidence that in-vehicle videotaping expedites
      the case disposition process is somewhat equivocal. Arrests that are videotaped
      lead to somewhat more speedy case resolutions overall, but also to higher implied
      consent hearing request rates and presumably more officer time invested in
      implied consent hearings. In other words, results suggest that videotapes may
      delay or complicate the process in some instances, but they more often lead to
      earlier case resolution.

PMID- 10084622
TI  - Impact forces following the unexpected removal of a chair while sitting.
AB  - This report documents the impact forces measured during trials of dropping an
      anthropometric dummy (80.3 kg) (Hybrid III, First Technologies Corporation) in
      three different positions onto it's pelvis (gluteal region) from a seated height,
      which was meant to simulate a chair being pulled out from an individual in the
      process of sitting. Peak forces on the pelvis were measured by a force plate
      covered with industrial carpet. These impact forces were translated to the
      compressive and shear forces on the lumbar spine. The peak impact forces during
      the different body postures were 20000-29900 N (torso upright); 13000-22200 N
      (torso-legs 45 degrees to floor); 6000-15200 N (layout position). The impact
      forces generated from falling onto the pelvis from a seated height, appear to be
      sufficient to cause injury as the forces well exceed documented injury tolerance
      levels.

PMID- 10084623
TI  - An economic evaluation of incremental resources to road safety programmes in New
      Zealand.
AB  - Road crashes are related to the level of traffic, road and weather conditions,
      and most importantly, road user behaviour, which is a function of the level of
      enforcement, education and advertising campaigns. Safety programmes such as
      enforcement and advertising campaigns against drink-driving, speeding or seatbelt
      wearing aim to improve road user behaviour, and thereby to reduce the number and
      severity of crashes. This paper estimates incremental safety outcomes of these
      programmes over time and compares them with their resource costs. Due to the
      common outcome of several programmes, it is difficult to identify the effects of
      individual programmes. This paper tries to separate out the effects of non
      roading safety programmes as a group from roading improvements. The analysis
      shows that safety programmes in New Zealand produce high incremental returns.
      Given that the crash risks in New Zealand are high in comparison with most other
      OECD countries, there is considerable scope for improvements to be made. The high
      incremental benefit/cost ratio over time supports this view and indicates that
      the investment in safety programmes is well below the optimal level.

PMID- 10084624
TI  - Road accident statistics: discrepancies between police and hospital data in a
      French island.
AB  - In most developed countries, information on road crashes are routinely collected
      by the police. However, comparison of police records and hospital data underlines
      a deficit of the number of road accidents in the routine statistics. In La
      Reunion, a French overseas dependency, an epidemiological study of injuries
      leading to hospitalisation or deaths has been performed from June 1993 to June
      1994. The comparison between hospital data and police records showed that only
      37.3% of non-fatally traffic-injured in-patients were recorded by the police.
      Length of stay in hospital, physician in charge of the first aid, urban place of
      the crash, type of vehicle involved, day and time of the crash and blood alcohol
      concentration were significantly associated with the presence in the police file.
      Police overestimated the severity of the injuries. Police notified 100 deaths on
      the 115 counted by the study. In France, non-fatally traffic-injured should be
      followed 30 days to improve quality of police death records. A capture-recapture
      method was used to estimate the total number of injured people. The capture
      recapture method consists in merging information from several sources of
      notification to determine the real number of cases in the population and the
      exhaustivity of each source. We estimated that 346 subjects were injured in one
      month whereas police data recorded only 87 and hospital data 137. This method
      seems interesting to use in routine after validation when unique personal
      identifiers are available.

PMID- 10084625
TI  - Analysis of the structural behavior of the pelvis during lateral impact using the
      finite element method.
AB  - In this study, three-dimensional finite element models were created from computer
      tomography data to study lateral impact fractures of the pelvis. The models
      reflect the complex geometry and material properties of the pelvis. The models
      were compared to published experimental results for validation. Dynamic analyses
      of the pelvic structure were performed for different peak forces in the range of
      5520 to 15550 N to correspond to the velocities and impulses of real world
      accidents. The locations of structurally significant regions of the pelvis were
      identified based upon the stress distribution and upon the energy stored by the
      pelvis to failure. The impact force which induced fracture of the pelvic bone was
      8610 N. The region which failed first in left lateral impact was the right pubic
      ramus. The fracture pattern was a variant of the lateral compression pelvic
      injury. The results suggest that the anterior structures of the pelvis are the
      most sensitive regions. The energy absorbed by the pelvis prior to failure was
      8.98 J. The finite element method may be used to determine the strength and
      energy-absorbing capability of the pelvis for lateral impact loading.

PMID- 10084626
TI  - Visual functions of drivers involved in traffic accidents.
AB  - Eye functions were studied in 56 drivers who had recently been involved in
      traffic accidents. There were 17 women and 39 men in the study group, aged 20-87
      years. The traffic accidents had happened in intersections and city streets, in
      parking places and on highways. In seven drivers, a visual impairment was found:
      two drivers had strabismus and low visual acuities in one or both eyes, two had
      considerable hyperphoria, and three had a deutan color vision defect. However,
      comparing the type of accident to the defective eye functions showed no probable
      correlation.

PMID- 10084627
TI  - The effects on accidents of studded tires and laws banning their use: a meta
      analysis of evaluation studies.
AB  - Studies that have evaluated the effects on accidents of studded tires are
      reviewed. There are two types of evaluation studies with respect to the safety
      effects of studded tires: (1) Studies of the effect on automobile accident rates
      of using studded tires; and (2) studies of the effect on accidents of banning the
      use of studded tires. The results of studies of the effects of studded tires on
      automobile accident rates are found to vary substantially, depending on the
      quality of the study design. Recent studies employing multivariate techniques of
      analysis to control for confounding factors, attribute to studded tires minor
      declines in automobile accident rates of 5% for snow- or ice-covered roads, 2%
      for bare roads and 4% for all road surfaces combined. The results of these
      studies are consistent with the most recent estimates of the effect on accidents
      of banning studded tires. It is concluded that studded tires probably confer a
      slight safety benefit during wintertime.

PMID- 10084628
TI  - An inter-regional comparison: fatal crashes in the southeastern and non
      southeastern United States: preliminary findings.
AB  - The southeastern United States, particularly those states representing the
      National Highway Traffic Safety Administration's and Federal Highway
      Administration's Region IV, have consistently had among the highest number of
      fatal crashes and fatal crash rates compared to the other five regions in the US.
      These states--Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina,
      South Carolina, and Tennessee, are suspected of sharing traits in common that
      lead to their systematically poor crash record. Inter-regional and intra-regional
      comparisons, such as the comparison between southeastern and non-southeastern
      states, raises interesting and challenging research questions that are applicable
      to similar comparisons. First, is there a sound practical and theoretical
      justification supporting an inter-regional comparison framework? Second, is there
      a way to construct a meaningful statistical hypothesis and test to determine
      whether one region, which is comprised of numerous entities, suffers from a
      characteristically better or worse crash record? This paper addresses each of
      these questions. After providing a brief summary of the Southeast's safety
      record, we discuss the issues pro and con surrounding inter-regional comparisons,
      illustrating the statistical strategy for such an analysis approach. Then, a
      simple generalizable statistical procedure is used for testing the hypothesis
      that southeastern states have a poorer crash record than non-southeastern states.
      Finally, we explore possible relationships between safety belt use, roadway
      functional class, vehicle miles of travel, and driver age on fatal crash
      occurrence. The data used in the analyses are from the Fatal Analysis Reporting
      System (FARS), primarily data compiled for 1995. The analysis suggests that
      regional differences in fatal crashes may indeed exist, that these differences
      are related in part to seat-belt use, VMT by functional classification, and speed
      limit differences, and that more detailed studies are needed to quantify the
      effect of these and other factors. The approach developed here lends insight as
      to where future in-depth studies may reveal causal factors of fatal crashes, and
      illustrates the relative safety performance records of US regions.

PMID- 10084629
TI  - Development of a standardized boating sobriety test.
AB  - A sobriety test capable of being administered on boats was developed as an aid in
      establishing probable cause to request a breath sample of recreational boat
      operators suspected of being over the legal alcohol limit. In a laboratory phase
      some 12 candidate measures suitable for use in a boating environment were
      assessed for their relationship to blood alcohol levels through administration to
      32 subjects tested at blood alcohol concentrations (BACs) of 0.00, 0.06 and
      0.12%. Four measures showing significant relationships to BAC were then
      administered by marine police to a sample of 60 recreational boaters found to
      have BACs ranging from 0.0 to 0.20%. Three measures still showing significant
      relationships to alcohol were horizontal gaze Nystagmus given in a seated
      position, reciting the alphabet from A to Z, and clapping hands alternately with
      palm and back of hand, while counting. Correlation of the measures with BAC, and
      the ability to distinguish boaters over and under a 0.10% limit were similar to
      those found over the same BAC range with the standardized field sobriety test
      (SFST) for motor vehicle operators. Where there is not sufficient cause to
      request a boat operator to proceed to shore for testing, a standardized boating
      sobriety test (SBST) making use of the three measures appears to be a suitable
      replacement for the SFST.

PMID- 10084630
TI  - Farm work related fatalities among adults in Victoria, Australia: the human cost
      of agriculture.
AB  - The purpose of this study was to review the patterns of, and trends in, farm work
      related fatalities among adults in one Australian state for the period 1985-1996.
      Fatality data was provided by the Victorian Workcover Authority Health and Safety
      Division. Trends were determined using regression techniques assuming a Poisson
      error structure for annual fatality rates. Results showed an annual average of
      eight deaths. Males, and those 60 years and over, were over-represented, compared
      to persons employed. Tractor incidents were the most common type of fatality
      (72%), with tractor roll overs accounting for 61% of all tractor incidents. Non
      tractor fatalities included being hit by a falling object and transport
      incidents. Statistical trend analyses revealed a non significant decrease in the
      tractor roll over fatality rate, and significant increases in the all farm (P =
      0.004) and non tractor fatality rates (P = 0.036). The 3 year moving average rate
      for non tractor farm fatalities has increased to the point where it exceeds that
      for tractor roll over fatalities, and is approaching that for all tractor
      fatalities. Changes within the agricultural industry, coupled with the ageing of
      the farm workforce, appear to placing Victorian farmers at increased risk of farm
      work related death.

PMID- 10084631
TI  - Speed, speed limits and road traffic accidents under free flow conditions.
AB  - The relationship between various measures of traffic speed, under free flow
      conditions, and accident rate is investigated for two groups of sites, one in the
      Tyne and Wear county of the UK and the other in Bahrain. The effect of speed
      limits on traffic speed is estimated for both groups of sites. In Bahrain, there
      is statistically significant evidence of an association between mean speed and
      accident rate. In Tyne and Wear the statistical evidence is weaker, and points to
      a stronger relationship between accidents and the variability of traffic speeds.
      In both areas, there is an apparent decrease in accident rate if the percentage
      of heavy vehicles increases, with the speed distribution held constant. In both
      areas the effect of speed limits is to reduce the mean speed of traffic by at
      least one quarter. Higher speeds are associated with longer trips.

PMID- 10084632
TI  - Substance P and the neurokinins: novel peptide neurotransmitters in
      psychopharmacology.
AB  - A new neurotransmitter system is a family of 3 related peptides known as
      neurokinins. The best known of these is substance P. The others are known simply
      as neurokinin A and neurokinin B. The specific receptor subtypes that correspond
      to these 3 neurokinins are neurokinin 1 receptors for substance P, neurokinin 2
      receptors for neurokinin A, and neurokinin 3 receptors for neurokinin B. These
      neurotransmitters appear to play a key role in the regulation of emotions, and
      antagonists of their receptors may be novel psychotropic drugs of the future.

PMID- 10084633
TI  - A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients
      with bipolar I depression. Lamictal 602 Study Group.
AB  - BACKGROUND: More treatment options for bipolar depression are needed. Currently
      available antidepressants may increase the risk of mania and rapid cycling, and
      mood stabilizers appear to be less effective in treating depression than mania.
      Preliminary data suggest that lamotrigine, an established antiepileptic drug, may
      be effective for both the depression and mania associated with bipolar disorder.
      This is the first controlled multicenter study evaluating lamotrigine monotherapy
      in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I
      disorder experiencing a major depressive episode (DSM-IV, N = 195) received
      lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric
      evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the
      Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the
      Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I)
      were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated
      significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS,
      CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week
      3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on
      several measures. The proportions of patients exhibiting a response on CGI-I were
      51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo
      groups, respectively. Adverse events and other safety results were similar across
      treatment groups, except for a higher rate of headache in the lamotrigine groups.
      CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment
      for bipolar depression.

PMID- 10084634
TI  - Paroxetine in the treatment of primary insomnia: preliminary clinical and
      electroencephalogram sleep data.
AB  - BACKGROUND: Primary insomnia is a persistent and recurrent disorder as well as a
      risk factor for depression. The goal of this study was to determine whether
      paroxetine, a nonsedating antidepressant, would be effective in the treatment of
      patients with primary insomnia. METHOD: Fifteen patients meeting DSM-IV criteria
      for primary insomnia received paroxetine at bedtime for 6 weeks in an open,
      flexible-dose trial (median dose = 20 mg). Patients were assessed with daily
      sleep diaries, baseline and treatment polysomnography, and weekly standardized
      clinical evaluations. RESULTS: Of the 14 patients who completed the study (1
      dropped out owing to side effects), 11 improved with treatment, and 7 of these 11
      no longer met diagnostic criteria for insomnia. Although self-reported sleep
      quality (measured by the Pittsburgh Sleep Quality Index) and daytime well-being
      (measured by the Profile of Mood States) improved with treatment, the quantity of
      sleep, measured by diary and by polysomnography, did not change consistently with
      these improvements. Power spectral analysis suggested that paroxetine treatment
      may be associated with decreases in power in frequencies within the delta and
      alpha frequency ranges. CONCLUSION: These results support the effectiveness of
      paroxetine in the acute treatment of primary insomnia. Further evaluation with
      controlled and longitudinal designs is warranted.

PMID- 10084635
TI  - Nefazodone in social phobia.
AB  - BACKGROUND: A variety of drug treatments have been shown to be effective in the
      treatment of social phobia. This study attempted to assess the efficacy of
      nefazodone, a new novel serotonergic drug, in the treatment of social phobia.
      METHOD: Nefazodone was administered to 23 patients who had a primary DSM-IV
      diagnosis of social phobia, generalized type (diagnosed by the Structured
      Clinical Interview for DSM-IV), in a 12-week open clinical trial. Treatment began
      at 100 mg of nefazodone daily and was increased according to clinical response
      and side effects. Patients completed self-report measures at baseline and at
      weeks 4, 8, and 12. These measures included the Fear of Negative Evaluation
      scale, the Social Avoidance and Distress scale, the Social Anxiety Thoughts
      Questionnaire, the Fear Questionnaire, the State-Trait Anxiety Inventory, the
      Beck Depression Inventory, the Social Adjustment Scale Self-Report, and the
      Sheehan Disability Scale. Clinicians completed the Liebowitz Panic and Social
      Phobic Disorders rating form and the Brief Social Phobia Scale. RESULTS: Twenty
      one of the 23 patients completed the 12-week trial. Sixteen (69.6%) were
      considered responders (moderate or marked improvement), and 7 (30.4%) were
      considered to be nonresponders (minimal improvement or no change in symptoms).
      Measures of social anxiety, social phobic avoidance, depression, and social
      functioning showed a statistically significant change at endpoint. CONCLUSION:
      These findings support a role for nefazodone in the treatment of social phobia,
      generalized type. Controlled studies will be required to further investigate this
      preliminary finding as well as to compare nefazodone with other pharmacologic
      treatments of social phobia.

PMID- 10084636
TI  - A review of the efficacy of selective serotonin reuptake inhibitors in obsessive
      compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic illness associated
      with substantial morbidity; it often requires long-term medication. The best
      studied therapeutic agent in the treatment of this disorder is the tricyclic
      antidepressant clomipramine. Since other tricyclic antidepressants appear to lack
      efficacy in OCD, that of clomipramine has been linked to its potent effects on
      serotonin. Consequently, agents that selectively inhibit serotonin reuptake have
      been the focus of several large-scale, placebo-controlled studies of OCD. Their
      efficacy in OCD is the focus of our review. DATA SOURCES: MEDLINE search (1966 to
      present) of OCD treatment with clomipramine or SSRI antidepressant medication
      using the key words obsessive-compulsive disorder, serotonin reuptake inhibitors,
      clomipramine, and pharmacology. STUDY FINDINGS: The selective serotonin reuptake
      inhibitors fluoxetine, sertraline, fluvoxamine, and paroxetine have, in separate
      multicenter trials, demonstrated efficacy and tolerability in the treatment of
      OCD. In contrast, clomipramine, though efficacious, is often associated with
      substantial adverse events, particularly anticholinergic side effects. While 2
      recent meta-analyses support the superior efficacy of clomipramine over selective
      serotonin reuptake inhibitors in the treatment of OCD, 5 of 6 head-to-head
      comparisons of either fluoxetine or fluvoxamine versus clomipramine have found
      similar efficacy but a lower incidence of side effects with the selective
      serotonin reuptake inhibitor. A recently completed multicenter, 12-week, double
      blind trial of paroxetine versus clomipramine versus placebo showed paroxetine to
      be as effective as clomipramine. With significantly fewer dropouts due to adverse
      effects than clomipramine, paroxetine was also associated with superior
      tolerability. CONCLUSION: The suggestion that selective serotonin reuptake
      inhibitors possess efficacy similar to that of clomipramine, but have a superior
      side effect profile, may have important implications for patients with OCD who
      require long-term treatment.

PMID- 10084637
TI  - Comparison of risperidone and placebo for psychosis and behavioral disturbances
      associated with dementia: a randomized, double-blind trial. Risperidone Study
      Group.
AB  - BACKGROUND: We report the findings from the first large, double-blind, placebo
      controlled study conducted to evaluate the efficacy and safety of risperidone in
      the treatment of psychotic and behavioral symptoms in institutionalized elderly
      patients with dementia. METHOD: 625 patients (67.8% women; mean age = 82.7 years)
      with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or
      mixed dementia (12%) and significant psychotic and behavioral symptoms were
      included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1
      mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was
      the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD).
      RESULTS: The study was completed by 70% of the patients. Baseline Functional
      Assessment Staging scores were 6 or 7 in more than 95% of the patients,
      indicating severe dementia. At endpoint, significantly greater reductions in
      BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen
      in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p =
      .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was
      superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More
      adverse events were reported by patients receiving 2 mg/day of risperidone than 1
      mg/day. The most common dose-related adverse events were extrapyramidal symptoms,
      somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms
      in patients receiving 1 mg/day of risperidone was not significantly greater than
      in placebo patients. CONCLUSION: Risperidone significantly improved symptoms of
      psychosis and aggressive behavior in patients with severe dementia. Results show
      that 1 mg/day of risperidone is an appropriate dose for most elderly patients
      with dementia.

PMID- 10084638
TI  - Olanzapine response in psychotic depression.
AB  - BACKGROUND: Psychotic depression is more common than is generally realized,
      occurring in an estimated 16% to 54% of depressed patients. In controlled studies
      of patients with schizophrenia, the atypical antipsychotic olanzapine has been
      shown to be superior in efficacy to haloperidol at doses of 10 mg/day. Since
      olanzapine may have antidepressant effects in addition to its antipsychotic
      properties, the purpose of this study was to assess the safety and efficacy of
      olanzapine in the treatment of psychotic depression. METHOD: Hospitalized
      patients with the discharge diagnosis of DSM-IV psychotic depression (major
      depression with psychotic features or bipolar I disorder, depressed phase...with
      psychotic features) who had been treated with olanzapine during the first 9
      months of its availability in the United States were identified. An age- and sex
      matched sample of hospitalized patients with psychotic depression treated with
      other antipsychotics during the same time period was also identified. The medical
      records were expunged of all references to medication treatment and then reviewed
      and scored in a blind fashion for indications, doses, response, and side effects.
      RESULTS: Fifteen psychotic depression patients (10 women, 5 men), aged 36.9 +/-
      10.1 years, who were treated with olanzapine were retrospectively compared with
      15 psychotic depression patients (10 women, 5 men), aged 35.0 +/- 8.2 years,
      treated with other antipsychotics. Ten (67%) of 15 patients taking olanzapine
      were much or very much improved upon discharge compared with only 4 (27%) of 15
      patients taking other antipsychotics (Fisher exact test, p = .037). Olanzapine
      was well tolerated: no patient discontinued the medication because of side
      effects. Twelve (80%) of 15 patients in each group were taking antidepressants in
      addition to the antipsychotic. Of the 3 patients taking olanzapine but not taking
      an antidepressant, 2 were much or very much improved (1 patient taking olanzapine
      alone, 1 taking olanzapine plus valproate sodium). CONCLUSION: Olanzapine appears
      to be effective and safe for patients with psychotic depression. Further
      prospective studies are warranted to ascertain whether olanzapine's unique
      pharmacologic profile may make it particularly useful for the treatment of
      psychotic depression either alone or in combination with antidepressants.

PMID- 10084639
TI  - Olanzapine treatment after clozapine-induced granulocytopenia in 3 patients.
AB  - BACKGROUND: How to best treat psychotic patients who have had past clozapine
      induced agranulocytosis or granulocytopenia remains a problem. CASE REPORTS: We
      report 3 patients with chronic schizophrenia who had previously stopped clozapine
      due to hematologic side effects. The patients evidenced improvement with
      olanzapine that equated to 16- to 31-point decreases in rating scale scores
      during 1-year follow-up without any hematologic abnormalities. CONCLUSION: The
      results suggest that olanzapine may be useful in treating patients with clozapine
      induced granulocytopenia without the risk of recurrence of hematologic side
      effects.

PMID- 10084640
TI  - Manufacturer support and outcome.

PMID- 10084641
TI  - Early augmentation of sertraline with methylphenidate.

PMID- 10084642
TI  - Visual field "shimmering" associated with nefazodone.

PMID- 10084643
TI  - Pharmacists lack knowledge of antidepressant discontinuation symptoms.

PMID- 10084644
TI  - Hyperprolactinemia and male sexual dysfunction.

PMID- 10084645
TI  - Fertility and reproduction in women with anorexia nervosa: a controlled study.
AB  - BACKGROUND: Women who have anorexia nervosa may experience difficulties with
      fertility and reproduction. METHOD: We examined fertility and reproductive
      history in 66 women who had a history of anorexia nervosa (DSM-III-R) and 98
      randomly selected community controls as part of a follow-up investigation
      examining the course of anorexia nervosa. RESULTS: Although women with a history
      of anorexia nervosa and controls did not differ on rate of pregnancy, mean number
      of pregnancies per woman, or age at first pregnancy, women with anorexia nervosa
      had significantly more miscarriages and cesarean deliveries, and the offspring of
      women with anorexia nervosa were significantly more likely to be born prematurely
      and were of lower birth weight than offspring of controls. There were no
      differences between women with active versus remitted anorexia nervosa on any of
      these measures; however, offspring of anorexic women with no history of bulimia
      nervosa had significantly lower body weight than offspring of anorexic women with
      a lifetime history of bulimia nervosa. CONCLUSION: Our results argue for
      intensive prenatal care for women with both active and remitted anorexia nervosa
      to ensure adequate prenatal nutrition and fetal development.

PMID- 10084646
TI  - Is cryosurgery appropriate treatment for hepatic malignancies?

PMID- 10084647
TI  - 30 Gy may be an adequate dose in patients with anal cancer treated with
      excisional biopsy followed by combined-modality therapy.
AB  - BACKGROUND AND OBJECTIVES: There are a subset of patients with invasive anal
      cancers who undergo an excisional biopsy either before or after combined-modality
      therapy (CMT). The objective of this study is to determine whether these patients
      can be adequately treated with a lower dose of pelvic radiation therapy. METHODS:
      A total of 25 patients were treated with CMT either before or after an excisional
      biopsy. The four subsets included 8 patients with initial excision followed by
      CMT with 30-34 Gy (EX/30), 6 patients with initial excision followed by CMT with
      45-50.4 Gy (EX/45), 10 patients treated by CMT with 30 Gy followed by an excision
      (30/EX), and 1 patient by CMT with 45 Gy followed by an excision (45/EX).
      RESULTS: For the total group, the actuarial 5-year disease-free survival was 78%,
      overall survival was 86%, colostomy-free survival was 91%, and local control was
      82%. When patients received CMT either before or following an excision, the
      actuarial local control and survival results with 30-34 Gy vs. 45-50.4 Gy were
      similar. In contrast to radiation dose, in patients who received 30-34 Gy, the
      sequence of the excision (before or after CMT) did appear to have a borderline
      significant impact on local control. Actuarial 5-year local control was 100% for
      EX/30 vs. 67% for 30/EX (P = 0.08). CONCLUSIONS: Because of the small number of
      patients in each group and the retrospective nature of the analysis, it is
      difficult to draw definitive conclusions from this study. However, our data
      suggest that in patients who are selected to undergo an initial excisional biopsy
      followed by CMT, 30 Gy may be an adequate radiation dose. Local control may be
      higher in patients who undergo an excisional biopsy followed by CMT compared with
      the converse.

PMID- 10084648
TI  - Clinicopathological features of primary gastric lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Surgery has been the mainstay of the treatment of
      primary gastric lymphoma, but the value of surgical treatment needs reevaluation.
      METHODS: Thirty-two patients with primary non-Hodgkin B-cell lymphoma of the
      stomach were examined retrospectively to evaluate prognostic factors and their
      impact on survival. All patients had undergone abdominal exploration for radical
      surgery between 1979 and 1992. The prognostic factors in view of survival after
      treatment were determined with both univariate and multivariate analyses.
      RESULTS: The resectability rate was 66% (21/32) and radical resections had been
      performed on 53% (17/32). The overall median survival was 65 months and the
      overall 5-year survival was 56%. The 5-year survival rates related to a modified
      Ann Arbor classification as follows: I 1E, 86%; I 2E, 100%; II 1E, 44%; II 2E,
      37%; IIIE, 20%; and IVE, 0%. Univariate analysis using Kaplan-Meier estimates
      showed that radical surgery, Ann Arbor stage, patient's age, and lymph node
      involvement were significant prognostic factors. According to Cox proportional
      regression analysis, only Ann Arbor stage, radical surgery, and age were
      significant independent variables. CONCLUSIONS: According to our experience,
      surgery is still needed for the treatment of primary gastric lymphomas, but the
      benefits of primary chemotherapy or adjuvant chemotherapy using cytotoxic drugs
      must be determined in large prospective controlled trials.

PMID- 10084649
TI  - Tyrosine kinase inhibitors as antiproliferative agents against an estrogen
      dependent breast cancer cell line in vitro.
AB  - BACKGROUND AND OBJECTIVES: Receptor tyrosine kinase (RTK) activation is critical
      for growth factor-mediated cell proliferation. Blockade of RTK activation
      inhibits growth factor-induced cell proliferation. A panel of RTK inhibitors
      (tyrphostins) have been tested and compared for their antiproliferative effects
      on the hormone-dependent human breast cancer cell line, MCF-7, in vitro. METHODS:
      MCF-7 cells (10(4)/well) were seeded into 96 well plates and maintained in DMEM
      with 1% bovine serum albumin (BSA), 200-pg/mL estrogen, or 10% fetal bovine
      serum. After a defined time interval, the cells were exposed to RTK inhibitors
      and a non-RTK-inhibitory analog of tyrphostins (0 to 400 microM). After 3 days,
      the number of viable cells in each well was estimated by an MTT assay and the
      results expressed as percent of controls. Using a representative tyrphostin, A47,
      the validity of MTT assay as a measure of cell proliferation was tested by a
      colony formation assay and by immunostaining with Ki-67 antibodies. RESULTS: MCF
      7 cells maintained in DMEM containing 1% BSA without E2 or serum showed a minimal
      increase in cell number. Supplementation with E2 stimulated cell proliferation in
      a dose-dependent manner. This E2-mediated growth stimulation was completely
      inhibited (cytostatic effects) by the epidermal growth factor receptor (EGFR)
      selective tyrphostins A47, B48, RG13022, and B50. These same tyrphostins also
      decreased the cell numbers to below control numbers in cultures maintained in 1%
      BSA or in serum containing medium (cytostatic/cytotoxic effects). B44 (EGFR
      selective tyrphostin), AG1295 (platelet-derived growth factor receptor [PDGFR]
      selective tyrphostin), and A1 had no inhibitory effects on cells with or without
      E2 treatments. However, A1 inhibited cell growth under serum supplementation.
      Genistein, a phytoestrogen, stimulated the autonomous, E2-induced as well as
      serum-induced growth of MCF-7 cells. Cell proliferation results derived from the
      MTT assay were corroborated by both the colony formation assay as well as the Ki
      67 assay. CONCLUSIONS: Of the agents tested, only EGFR-selective tyrphostins
      blocked E2-stimulated tumor cell proliferation, as opposed to the PDGFR-selective
      tyrphostin, RTK noninhibitory agent, or the phytoestrogen, genistein, which did
      not exert such an effect. These findings suggest that epidermal growth factor
      (EGF) is an important mediator of E2-induced proliferation of MCF-7 cells. Thus,
      tyrphostins may be selectively used to prevent the growth of hormone-dependent
      breast cancers, particularly regrowth of residual tumor in postmenopausal breast
      cancer survivors receiving estrogen replacement therapy.

PMID- 10084650
TI  - Free-to-total prostate-specific antigen ratios 18-24 months following external
      beam radiation for adenocarcinoma of the prostate.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate free-to
      total prostate-specific antigen (PSA) ratios after definitive external beam
      radiation therapy for men with adenocarcinoma of the prostate (CaP). METHODS: A
      prospective evaluation of percent free PSA in men following definitive external
      beam radiation therapy for CaP was compared to men with untreated CaP and men at
      very low risk for CaP. Statistical comparison of clinical and pathologic
      parameters was performed. RESULTS: There was no statistically significant
      difference in free-to-total PSA ratios for men with newly diagnosed CaP and men
      with detectable PSA who were treated with external beam radiation therapy.
      CONCLUSIONS: Free-to-total PSA ratios after definitive external beam radiation
      therapy for CaP are consistent with percent free PSA in patients with newly
      diagnosed CaP. This supports the theory that PSA from in situ prostate tissue
      following external beam radiation therapy is produced by malignant cells.

PMID- 10084651
TI  - Primary tumors of the mediastinum.
AB  - BACKGROUND AND OBJECTIVES: Diagnostic and therapeutic approaches to mediastinal
      tumors have changed over the past three decades. We reviewed our recent
      experience with these tumors and assessed the role of a multidisciplinary
      treatment approach. METHODS: A retrospective review of 124 patients with primary
      mediastinal tumors over a 25-year period. RESULTS: Median age was 35 years.
      Symptoms were present in 86 of 124 (69%) patients. One hundred and eleven of 124
      (90%) tumors were malignant. Distant metastases were present at diagnosis in 14
      of 124 (11%) patients. The most common tumor was thymoma (38/124, 31%), followed
      by germ-cell tumor (29/124, 23%), lymphoma (24/124, 19%), and neurogenic tumors
      (15/124, 12%). Seventy-four of 124 (60%) patients underwent resection, 88 (71%)
      received chemotherapy, and 97 (78%) received radiation therapy. Tumor recurrence
      occurred in 52% (47/91) of patients who initially had a complete resection or
      response to treatment. Median time to recurrence was 10 months. Overall median
      survival was 44 months. Metastatic disease at presentation (P = 0.02) and tumor
      recurrence (P = 0.00001) were the only significant independent predictors of
      survival on multivariate analysis. CONCLUSIONS: Malignant primary mediastinal
      tumors often require multimodality treatment. Despite improvements in survival
      with multimodality treatment, death from recurrent disease remains a problem.

PMID- 10084652
TI  - Potential utility of sentinel node biopsy in the original surgical assessment of
      Hurthle cell tumors of the thyroid: 23-year institutional review of Hurthle cell
      neoplasms.
AB  - BACKGROUND AND OBJECTIVES: Great difficulty still exists in determining the
      potential malignancy of Hurthle cell tumors of the thyroid gland. Indications for
      the extent of resection vary greatly in the reported literature. Sentinel node
      biopsy has shown its usefulness as a prognostic indicator in both melanoma and
      breast cancer. The feasibility of using it as an integral part of Hurthle cell
      tumor surgery was investigated and is discussed. METHODS: Eleven patients
      diagnosed with Hurthle cell tumors between the years of 1975 and 1998 were
      reviewed. The last three patients had sentinel node biopsy with isosulfan blue
      dye as an integral part of their procedure. RESULTS: Sentinel node biopsy was
      accomplished without difficulty or complication in our last three patients. Two
      patients were considered to be benign by frozen section and final pathology.
      Their sentinel nodes were benign. One patient was considered malignant on both
      frozen and final pathology. His sentinel nodes as well as central node dissection
      revealed no lymphatic spread. CONCLUSIONS: Malignancy of Hurthle cell tumors of
      the thyroid is difficult to determine even on final pathological examination. The
      addition of nodal sampling may add valuable prognostic information. Sentinel node
      biopsy with isosulfan blue dye, although not previously reported for these
      tumors, appears to be a logical next step in the evolution of surgical
      management.

PMID- 10084653
TI  - Immunohistochemical expression of cytokeratins in intrahepatic cholangiocarcinoma
      and metastatic adenocarcinoma of the liver.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to identify a difference in
      immunostaining that might help to distinguish between primary and metastatic
      liver neoplasms. METHODS: We examined immunohistochemical expression of
      cytokeratins (CKs) 7, 8, 19, and 20 in 12 intrahepatic cholangiocarcinomas (ICCs;
      9 of the mass-forming and 3 of the infiltrating type), 25 metastatic colorectal
      carcinomas (MCCs), and 7 metastatic gastric carcinomas (MGCs) of the liver.
      RESULTS: CKs 7 and 19 were expressed in all ICCs of infiltrating type, while each
      was seen in 7/9 (77.8%) of mass-forming type. CK 7-positive/CK 20-negative was
      seen in 9/12 (75.0%) of ICCs and in none of the 25 MCCs, while CK 7-negative/CK
      20-positive was seen in 1/12 (8.3%) of ICCs and 20/25 (80.0%) of MCCs. No
      differences were observed between MGCs and ICCs. CONCLUSIONS: These results
      suggest that immunohistochemical staining for both CKs 7 and 20 is useful for the
      differential diagnosis of ICCs and MCCs, whereas phenotypic expression of CKs
      appears to be different between mass-forming and infiltrating types of ICCs.

PMID- 10084654
TI  - Relationship between magnitude of resection, complication, and prosthetic
      survival after prosthetic knee reconstructions for distal femoral tumors.
AB  - BACKGROUND AND OBJECTIVES: Limb-sparing surgery has become the preferred surgical
      treatment of malignant bone tumors. The objective of this study was to evaluate
      factors that influence the morbidity and outcome of prosthetic knee replacement
      after resection of malignant tumors of the distal femur. METHODS: Eighty-two
      patients who had a resection of malignant tumor of the distal femur and
      implantation of a segmental knee prosthesis (minimum follow-up, 2 years) were
      retrospectively reviewed. RESULTS: Twenty-nine patients (35%) underwent 32
      prosthetic revisions, 6 from perioperative wound complications, 13 from aseptic
      loosening, and 13 from other complications. The 3-, 5-, and 10-year Kaplan-Meier
      prosthetic survival rates were 82%, 71%, and 50%, respectively. On univariate
      analysis, patients who had more than 40% resection of the distal femur (P =
      0.010) and those who had all their vasti muscles resected (P = 0.011) had
      significantly worse prosthetic survivals than the others. On multivariate
      analysis, resection of more than 40% of the distal femur was a significant
      negative prognostic factor for prosthetic survival (P = 0.017). Aseptic loosening
      was the primary cause of late prosthetic failure. Differences in the magnitude of
      resection influenced prosthetic survivorship more than prosthetic design.
      CONCLUSIONS: In the distal femoral endoprosthetic replacement, higher short- and
      long-term complications were found after extensive resections. Aseptic loosening
      was the primary cause of prosthetic failure.

PMID- 10084655
TI  - Laparoscopic splenectomy for non-Hodgkin lymphoma.
AB  - BACKGROUND AND OBJECTIVES: The spleen is frequently involved in patients with non
      Hodgkin lymphoma (NHL). The indications for splenectomy in this disease include
      amelioration of symptoms from splenomegaly, correction of cytopenias, and the
      need to establish the diagnosis. The aim of this study was to determine the
      feasibility of laparoscopic splenectomy for patients with splenomegaly and NHL.
      METHODS: Retrospective review was made of patients who underwent laparoscopic
      splenectomy for suspected NHL. RESULTS: A total of 57 laparoscopic splenectomies
      have been performed in the lateral position; 9 of these patients had NHL. All
      patients had splenomegaly with a mean craniocaudal length of 17.8 cm and mean
      morcellated splenic weight of 765 gm. The mean operating-room time was 185 min,
      with a mean blood loss of 108 cc. None were converted to open splenectomy, and
      there was no mortality. The mean postoperative stay was 2-4 days. At a mean
      follow-up of 6.7 months, there have been no major complications or sepsis.
      CONCLUSIONS: Laparoscopic splenectomy is indicated in the setting of splenomegaly
      and suspected lymphoma. The operation is best performed in the lateral position,
      which is successful in patients with massive splenomegaly.

PMID- 10084656
TI  - Revision hip arthroplasty in patients with a history of previous malignancy.
AB  - BACKGROUND AND OBJECTIVES: The potential association between implants and
      malignancy has been discussed in the literature, but never as a cause of
      loosening of joint arthroplasty. METHODS: The records of all patients who
      underwent revision arthroplasty at our institution between 1992 and 1995 were
      reviewed. RESULTS: Among 93 patients who underwent revision hip arthroplasties,
      11 (11.8%) had a history of previous malignancy. At surgery, in 2 of these
      patients, metastasis was found to be the cause of loosening in the affected hip.
      CONCLUSIONS: When revision hip arthroplasty is considered, patients with a
      history of malignancy require attenuated pre-, intra-, and postoperative workup.
      Management algorithm in such cases is proposed.

PMID- 10084657
TI  - Unexplained decrease in measured oxygen saturation by pulse oximetry following
      injection of Lymphazurin 1% (isosulfan blue) during a lymphatic mapping
      procedure.
AB  - A rare case of alteration in measured pulse oximetry during a lymphatic mapping
      procedure for cervical carcinoma is reported. Over a 5-min period following
      injection of perilesional Lymphazurin 1% dye (3 ml total), a profound pulse
      oximetry desaturation was observed. Concomitant arterial blood gas determinations
      confirmed patient's well-being. Interaction of this agent's absorptive
      spectroscopy and wavelengths used to measure oxygen saturation by commercial
      pulse oximetry devices is suspected.

PMID- 10084658
TI  - Modeling of the parenchymous vascularization and perfusion.
AB  - RATIONALE AND OBJECTIVES: The authors sought to create a realistic model of the
      parenchymous vascularization and perfusion. METHODS: A three-dimensional vascular
      model has been developed that reproduces the growth process of a vascular tree
      (angiogenesis). This model follows physical laws related to blood flow in vessels
      (Poiseuille's law), takes into account anatomic constraints, and optimizes a cost
      function related to the blood volume. RESULTS: Vascular trees, the ramifications
      of which go from main arteries to small arterioles, were simulated. Vascular
      structures corresponding to either a normal tissue perfusion or an abnormal
      perfusion (for example, a local hypervascularization) were presented in three
      dimensions (volume rendering). Geometric and hemodynamic characteristics computed
      on these trees were consistent with those of real data found in the literature.
      The vascular model is also a good tool for studying the propagation of the
      contrast product in normal and abnormal vessels. CONCLUSIONS: The three
      dimensional vascular model presented in this article provides insight into the
      simulation and the understanding of anatomic or physiologic vascular
      modifications.

PMID- 10084659
TI  - Segmented 5 versus nonsegmented flow quantitation: comparison of portal vein flow
      measurements.
AB  - RATIONALE AND OBJECTIVES: Times of acquisition, mean velocities, mean flows, and
      their respective standard deviations provided by segmented and nonsegmented flow
      quantifications (FQ) were compared in the main portal veins of ten healthy
      adults. METHODS: The segmented FQ performed five phase-encoding lines per
      segment. The authors successively applied the two electrocardiogram-triggered
      techniques in the same slice perpendicular to the portal flow direction. Their
      measurements were compared in particular by means of the statistical analysis
      proposed by Bland and Altman. RESULTS: The segmented 5 FQ reduced the acquisition
      time by two compared with the nonsegmented FQ. The mean velocity and mean flow
      values of the two techniques were not significantly different. The standard
      deviations were similar. CONCLUSIONS: The segmented 5 FQ showed its major
      advantage in the portal vein: the acquisition time was reduced without any loss
      of accuracy or any uncertainty enhancement.

PMID- 10084660
TI  - Slice simulation from a model of the parenchymous vascularization to evaluate
      texture features: work in progress.
AB  - RATIONALE AND OBJECTIVES: To demonstrate the usefulness of a model of the
      parenchymous vascularization to evaluate texture analysis methods. METHODS:
      Slices with thickness varying from 1 to 4 mm were reformatted from a 3D vascular
      model corresponding to either normal tissue perfusion or local
      hypervascularization. Parameters of statistical methods were measured on
      16128x128 regions of interest, and mean values and standard deviation were
      calculated. For each parameter, the performances (discrimination power and
      stability) were evaluated. RESULTS: Among 11 calculated statistical parameters,
      three (homogeneity, entropy, mean of gradients) were found to have a good
      discriminating power to differentiate normal perfusion from hypervascularization,
      but only the gradient mean was found to have a good stability with respect to the
      thickness. Five parameters (run percentage, run length distribution, long run
      emphasis, contrast, and gray level distribution) were found to have intermediate
      results. In the remaining three, curtosis and correlation was found to have
      little discrimination power, skewness none. CONCLUSION: This 3D vascular model,
      which allows the generation of various examples of vascular textures, is a
      powerful tool to assess the performance of texture analysis methods. This
      improves our knowledge of the methods and should contribute to their a priori
      choice when designing clinical studies.

PMID- 10084661
TI  - In vivo tissue extracellular volume fraction measurement by dynamic spin-lattice
      MRI relaxometry: application to the characterization of muscle fiber types.
AB  - RATIONALE AND OBJECTIVES: The extracellular volume fraction (v) was estimated in
      leg rabbit muscles by MRI dynamic longitudinal relaxation rate (R1) relaxometry
      to distinguish between slow- and fast-twitch muscle fiber types. METHOD: The
      extracellular volume fraction was calculated from the dynamic increase of the
      longitudinal relaxation rate after intravenous administration of a gadolinium (Gd
      DTPA) contrast bolus, assuming a biexponential plasma concentration model.
      RESULTS: It has been shown that the extracellular volume fraction increases with
      the slow fiber content (oxidative type I); the maximal value (v = 0.186+/-0,018)
      was obtained in pure slow-twitch muscle fiber (100% type I). CONCLUSION: NMR
      extracellular volume estimates closely agree with those obtained using the more
      classic invasive isotopic method (99mTc-DTPA) carried out on the same rabbit
      strain and with data reported in the literature. The method has potential
      applications to characterize the pathophysiologic status of tissues. It is also
      applicable to a wide range of tissues and pathologies, in particular for the
      characterization of malignant tissues and their response to therapies.

PMID- 10084662
TI  - Real-time control of focused ultrasound heating based on rapid MR thermometry.
AB  - RATIONALE AND OBJECTIVES: Real-time control of the heating procedure is essential
      for hyperthermia applications of focused ultrasound (FUS). The objective of this
      study is to demonstrate the feasibility of MRI-controlled FUS. METHODS: An
      automatic control system was developed using a dedicated interface between the MR
      system control computer and the FUS wave generator. Two algorithms were used to
      regulate FUS power to maintain the focal point temperature at a desired level.
      RESULTS: Automatic control of FUS power level was demonstrated ex vivo at three
      target temperature levels (increase of 5 degrees C, 10 degrees C, and 30 degrees
      C above room temperature) during 30-minute hyperthermic periods. Preliminary in
      vivo results on rat leg muscle confirm that necrosis estimate, calculated on-line
      during FUS sonication, allows prediction of tissue damage. CONCLUSIONS. The
      feasibility of fully automatic FUS control based on MRI thermometry has been
      demonstrated.

PMID- 10084663
TI  - New hemodynamic approach to angiogenesis: color and pulsed Doppler
      ultrasonography.
AB  - RATIONALE AND OBJECTIVES: To determine the capacity of color and spectral Doppler
      ultrasonography (US) to quantify angiogenesis in vivo and to characterize low
      resistance intratumor blood flow. METHODS: Thirty-two tumors, xenografted into
      mice, were studied with Doppler US. The number of intratumor vessels visualized
      with color Doppler US was compared with the density of microvessels and the
      number of vessels >100 microm determined by histologic examination. The
      resistance index and the peak systolic velocities were evaluated. RESULTS: The
      number of intratumor vessels visualized by color Doppler US was correlated with
      the number of vessels >100 microm (P<0.001) determined histologically. When
      vessel density was >30, intratumor vessels were always detected by color Dopper
      US. The resistance index and peak systolic velocities were significantly lower in
      intratumor than in peritumor vessels. CONCLUSIONS: Color Doppler US evaluated
      tumor angiogenesis accurately. Spectral analysis confirmed the low resistance of
      intratumor blood flow.

PMID- 10084664
TI  - Global left ventricular cardiac function: comparison between magnetic resonance
      imaging, radionuclide angiography, and contrast angiography.
AB  - RATIONALE AND OBJECTIVES: Cardiac magnetic resonance imaging (MRI) has been shown
      to be a robust and noninvasive method to assess left ventricular (LV) cardiac
      function. This study sought to assess volumes and mass calculated with MRI using
      fast techniques for acquisition and postprocessing, and to compare results in
      terms of cost-effectiveness with those of radionuclide angiography (RNA) or
      contrast angiography (CA). METHODS: Thirty-five patients and 15 healthy
      volunteers were studied. All patients underwent an MRI examination during the
      same period that they underwent ventriculography (26 patients) or radiography (25
      patients). From 7 to 11 short-axis slices were acquired with a breath-hold fast
      gradient echo-segmented sequence from apex to base. Contours were drawn with an
      automated border detection software. RESULTS: Ejection fraction (EF) correlated
      well between modalities (r = 0.77, P<0.001, for MRI and RNA; r = 0.72, P< 0.001,
      for MRI and CA). CONCLUSIONS: Cardiac MRI is a fast and accurate technique for
      estimation of LV volumes, EF, and mass.

PMID- 10084665
TI  - Gadolinium-enhanced fast three-dimensional angiography of the neck: technical
      aspect.
AB  - RATIONAL AND OBJECTIVES: This study sought to assess the feasibility of a
      contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiographic
      sequence for imaging the cervical arteries. METHODS: Ninety-eight consecutive
      patients underwent contrast MR angiography using a 3D sequence in the coronal
      plane, including both carotid and vertebral arteries. Gadolinium was injected at
      the beginning of the sequence. When the contrast was not optimal, a second
      injection was performed 5 to 10 minutes later. Qualitative assessment was
      performed for each arterial portion in a consensus manner by three radiologists
      who judged contrast enhancement, imaging coverage, and artifacts. RESULTS: A
      second injection was required in 11 patients, and two examinations were not
      assessable because of motion artifacts. Among the vessels analyzed, 19% were not
      assessable owing to the limited coverage in 11% and to the low contrast in 9%.
      Carotid bifurcations were assessable in 95%, whereas vertebral arteries were
      visualized from their origins to their intradural portions in only 82% of cases.
      A longitudinal signal-void artifact was found in the center of the arterial lumen
      of carotid arteries in six patients. CONCLUSIONS: Contrast MR angiography
      constitutes a promising tool to assess cervical arteries. Some limitations
      including spatial resolution, timing of injection, and imaging coverage should be
      overcome in the near future.

PMID- 10084666
TI  - Automatic detection of left ventricular contours from cardiac cine magnetic
      resonance imaging using fuzzy logic.
AB  - RATIONALE AND OBJECTIVES: Gated cardiac cine magnetic resonance imaging provides
      accurate dynamic data of the left ventricular function. However, the manual
      extraction of important physiologic parameters such as myocardium wall thickness
      and left ventricular volumes is invariably time consuming and subjective. To
      reduce the variability and time constraints inherent in observer contour tracing,
      the authors developed an automatic left ventricle contour-detection method.
      METHODS: The purpose was to apply fuzzy logic-based automatic contour detection
      to identification of endocardial and epicardial borders in short-axis magnetic
      resonance images. The automatic contouring was compared with manual tracing using
      the calculated ejection fraction as the comparison criterion. RESULTS: A good
      correlation was found between the two approaches (r2 = 0.98). CONCLUSIONS: The
      ejection fraction can be obtained using this automatic contouring method.

PMID- 10084667
TI  - Failing arteriovenous hemodialysis fistulas: assessment with magnetic resonance
      angiography.
AB  - RATIONALE AND OBJECTIVES: The authors sought to evaluate prospectively magnetic
      resonance angiography (MRA) versus fistulography in the detection and
      characterization of complications associated with malfunctioning hemodialysis
      access fistulas (arteriovenous fistulas [AVF]). METHODS: Nineteen patients with
      clinical AVF dysfunction were studied by MRA and fistulography. Data from each
      study were collected prospectively and analyzed in a blinded manner. RESULTS: The
      main diagnosis was stenosis in eight patients, thrombosis in five patients (mural
      thrombosis with preserved flow in one), aneurysm without stenosis in two
      patients, and normal AVF in four patients. A hazy flow void, assumed to be
      related to turbulence, was observed in normal arterial anastomoses. When flow
      void was considered as a criterion of stenosis or thrombosis, one false-positive
      and one false-negative MRA study were determined, yielding a sensitivity and
      specificity of 92% and 86%, respectively. CONCLUSIONS: Magnetic resonance
      angiography is a feasible and sensitive technique with which to portray suspected
      malfunctioning hemodialysis access fistulas.

PMID- 10084668
TI  - Cortical intraoperative stimulation in brain tumors as a tool to evaluate spatial
      data from motor functional MRI.
AB  - RATIONALE AND OBJECTIVE: The purpose of this prospective, double-blind study was
      to correlate motor functional MRI (fMRI) with cortical brain mapping by
      intraoperative stimulation using 3D reconstructed images of the surface of the
      brain, and to validate the spatial data of fMRI in patients with brain tumors.
      METHODS: Fourteen patients with tumors of the rolandic region underwent
      functional MR mapping of the hand region and subsequently cortical mapping before
      tumor resection. Data obtained with fMRI and brain mapping were not known
      previously by the neurosurgeon and by the neuroradiologist, respectively (double
      blind study). RESULTS: In each case, the results of direct cortical mapping
      matched those obtained with fMRI, both positively and negatively, although the
      extent of the functional activations was larger than the area required to elicit
      the corresponding movement during intraoperative brain mapping. CONCLUSION: fMRI
      can be used before surgery to assess motor functional area in patients with
      rolandic tumors. More studies are needed to validate during surgery the real
      extent of fMRI activations.

PMID- 10084669
TI  - Characterization of choline compounds with in vitro 1H magnetic resonance
      spectroscopy for the discrimination of primary brain tumors.
AB  - RATIONALE AND OBJECTIVES: The authors sought to compare 1H magnetic resonance
      spectroscopy (MRS) spectra from extracts of low-grade and high-grade gliomas,
      especially with respect to the signals of choline-containing compounds. METHODS:
      Perchloric acid extracts of six high-grade and six low-grade gliomas were
      analyzed by 1H MRS at 9.4 Tesla. RESULTS: The signals of glycerophosphocholine
      (GPC) at 3.23 ppm, phosphocholine (PC) at 3.22 ppm, and choline (Cho) at 3.21 ppm
      were identified in both types of tumors. The absolute concentrations of all Cho
      containing compounds (GPC + PC + Cho) in high-grade and low-grade gliomas were
      significantly different. The relative contributions of each of the Cho-containing
      compounds to the total choline signal were also statistically different. For high
      grade gliomas, the choline signal is composed of GPC, PC, and Cho in a well
      balanced contribution, whereas in low-grade gliomas, the signal is largely due to
      GPC with a small involvement of PC and Cho. CONCLUSIONS: The differences in the
      concentration and the repartition of Cho-containing compounds seem to be a marker
      of high-grade gliomas. They could also help to discriminate between high- and low
      grade gliomas in some difficult cases, especially if there is histologic
      uncertainty between anaplastic astrocytomas and low-grade oligodendrogliomas.

PMID- 10084670
TI  - MRI dosimetry: a fast quantitative MRI method to determine 3D absorbed dose
      distributions.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) techniques seem to be
      very promising for 3D dosimetry studies, but long imaging acquisition time limits
      their use. A new fast T1 mapping protocol, easy to implement on a conventional MR
      imager, has been used to determine dose distributions on Fricke gels. METHODS:
      The method has been tested on manganese chloride (MnCl2) doped ferrous gelatin
      gels. The T1 measuring times range from 1 minute 40 seconds to 3 minutes 30
      seconds for a 256x256 matrix image. RESULTS: The two- and three-dimensional
      profiles agree with those obtained with conventional dosimetry techniques (ion
      chambers). The precision and the spatial resolution principally depend on the
      signal-to-noise ratio of the used imaging RF coil. For example, for a surface
      coil, the accuracy is about 2.5% with a 1.56 mm spatial resolution. CONCLUSION:
      These preliminary results support the feasibility of the proposed technique for
      accurate MRI dosimetry studies and also have potential for various clinical
      quantitative MRI applications.

PMID- 10084671
TI  - The beneficial influence of prior knowledge on the quantitation of in vivo
      magnetic resonance spectroscopy signals.
AB  - RATIONALE AND OBJECTIVES: This work concerns quantitation of in vivo magnetic
      resonance spectroscopy signals and the influence of prior knowledge on the
      precision of parameter estimates. The authors point out how prior knowledge can
      be used for experiments. METHODS: The Cramer-Rao lower bounds formulae of the
      noise-related standard deviations on spectral parameters for doublets and
      triplets were derived. Chemical prior knowledge of the multiplet structures was
      used. RESULTS: The benefit of chemical prior knowledge was estimated for doublet
      and triplet structures of arbitrary shape. Then, it was used to quantify in vivo
      31P time-series signals of rat brain. CONCLUSIONS: Analytic expressions of errors
      on parameter estimates were derived, enabling prediction of the benefit of prior
      knowledge on quantitation results. These formulae allow us to state, for a given
      noise level, if the quantitation of strongly overlapping peaks such as adenosine
      triphosphate multiplets can be performed successfully.

PMID- 10084672
TI  - Ferdinand Sauerbruch (1875-1951).

PMID- 10084673
TI  - Surgical techniques tested in humans are used to treat our pets.

PMID- 10084674
TI  - Common laparoscopic procedures in swine: a review.
AB  - Swine serve as excellent models for many laparoscopic procedures. As more
      operations are being performed laparoscopically, it is essential for the surgeon
      to have a good understanding of laparoscopic techniques. This manuscript reviews
      some commonly performed laparoscopic operations with an emphasis on models in
      swine. Porcine anatomy is generally similar to human anatomy with some minor
      differences. Practice on porcine models can help refine techniques and increase
      efficiency and skill.

PMID- 10084675
TI  - Vascular endothelial growth factor in porcine coronary arteries following balloon
      angioplasty.
AB  - The present study was a preliminary inquiry into the presence of vascular
      endothelial growth factor (VEGF) in a model of coronary artery response to
      injury. We examined domestic pigs who had received a diet enriched in saturated
      fat and cholesterol and undergone balloon angioplasty of one or more coronary
      arteries. Immunohistochemical analysis of the coronary arteries 2 months after
      injury revealed the presence of VEGF distributed throughout the media and
      neointima of the angioplasty lesions and in association with blood vessels in the
      adventitia and those vessels growing into the base of the neointima. VEGF was
      also detected in areas of dietary-induced intimal proliferation. This study
      provided the first immunochemical demonstration of VEGF occuring naturally in a
      pig model of coronary response to injury.

PMID- 10084676
TI  - Should colon-penetrating small missiles be removed? An experimental study of
      retrocolic wound tracks.
AB  - Small-fragment injury to the colon may occur in approximately 5% of battlefield
      casualties. The surgical management aims to reduce the risk of retrocolic
      infection and provide optimal conditions for colonic wound healing. This study
      aimed to quantify the risk of retrocolic infection. Steel fragments were fired
      through exteriorized porcine colon and caught in 20% gelatin. The fragments, and
      resultant tracks, were extracted and subjected to quantitative bacteriological
      examination to determine the extent of contamination. The median bacterial count
      for complete tracks was 1.2 x 10(4) CFU/g (interquartile range 1.8 x 10(3) to 2.7
      x 10(4)). Counts were highest in the initial 1 cm of the track and reduced along
      its length. This study does not support wound track excision or missile fragment
      removal in cases of retrocolic trauma following penetrating colonic injury.
      Either or both procedures will increase local trauma and are likely to prejudice
      colonic wound repair.

PMID- 10084677
TI  - Increased levels of surgical adhesions in TGFbeta1 heterozygous mice.
AB  - Adhesion formation and fibrosis represent a major complication of surgical
      intervention. Reducing the morbidity associated with adhesions requires an
      understanding of the mechanisms underlying their formation. Since increased
      levels of transforming growth factor-beta1 (TGFbeta1) have been associated with
      inflammation and adhesion production, we investigated the requirement of TGFbeta1
      in peritoneal adhesion formation utilizing mice carrying a targeted disruption of
      the TGFbeta1 allele. Mice that were either wild-type (+/+), containing two normal
      alleles of TGFbeta1, or heterozygous (+/-) for the TGFbeta1 null allele received
      injections of magnesium silicate (talc), and the extent of abdominal adhesions
      was determined utilizing a standard grading score. Wild-type (+/+) animals had at
      least twofold more TGFbeta1 protein in peritoneal fluids at 2 h posttrauma
      compared to heterozygous (+/-) mice (727 vs. 243 pg TGFbeta1/mg protein by enzyme
      linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had
      significantly less scar and adhesion formation (p < .05) at 7 days posttrauma
      (1.8 +/- 0.8 vs. 3.4 +/- 1.4, graded from 0 to 5, in +/+ and +/- mice,
      respectively). These results demonstrate that haploid insufficiency in TGFbeta1
      levels can lead to inappropriate matrix and adhesion production during
      inflammation, and together with previous studies suggest that any perturbation of
      normal TGFbeta1 levels can modulate the injury response that regulates the extent
      of adhesion formation.

PMID- 10084678
TI  - Beta-glucan reflects liver injury after preservation and transplantation in dogs.
AB  - Graft failure and extrahepatic organ complications, which frequently develop
      after transplantation, may be related to inflammatory mediators stimulated by
      endotoxin (ET). The role of endotoxemia after liver transplantation is
      controversial and may depend upon differences in the ET assay method used in the
      various contradicting studies. While the standard Limulus amebocyte lysate (LAL)
      is reactive for ET and beta-glucan, a novel turbidimetric assay method enables
      separate determinations of ET and beta-glucan. Beagle dogs undergoing orthotopic
      liver transplantation were divided into two groups. In Group I (n = 6) the grafts
      were transplanted immediately and in Group II (n = 6) grafts were preserved for
      48 h in University of Wisconsin (UW) solution. Animals received cyclosporine
      immunosuppression and were followed for 14 days. Daily measurements of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase
      (LDH) were performed. Samples for ET and beta-glucan measurement were collected
      serially and processed using the turbidimetric assay method. While no graft
      failure was seen in Group I, three of six Group II animals died from graft
      failure within 1 day after transplantation. Preservation and reperfusion injury
      was much more severe in the Group II grafts than in Group I grafts. While
      endotoxemia could not be detected, postoperative beta-glucan levels (undetectable
      pretransplant) were seen in both groups. Beta-glucan levels were much higher in
      Group II grafts than in Group I grafts, and correlated with the severity of liver
      damage. In conclusion, this study shows that beta-glucan, instead of ET, appears
      during the early posttransplant period. We believe that posttransplant elevation
      of beta-glucan is related to liver damage, especially endothelial damage by
      preservation and reperfusion.

PMID- 10084679
TI  - Anastomotic and regional blood flow following esophagogastrectomy in an opossum
      model.
AB  - Adenocarcinoma of the esophagus is increasing in incidence. The primary treatment
      is surgical resection, which is associated with considerable risk of anastomotic
      dehiscence and stricture. Decreased blood flow has been suggested as one of the
      factors contributing to these anastomotic failures. Our hypothesis was that
      anastomotic blood flow was decreased secondary to gastric and esophageal
      mobilization and would be increased by endogenous nitric oxide. Five opossums
      underwent esophagogastrectomy. Gastric and esophageal blood flow was measured
      following laparotomy, esophageal and gastric mobilization, esophagogastric
      resection and anastomosis, and L-arginine infusion. Radioactive microspheres were
      used to measure blood flow in the mucosa and muscularis of the esophagogastric
      anastomosis, esophagus, and stomach. Contrary to our hypothesis, blood flow in
      the anastomosis was maintained if not increased following esophagogastrectomy.
      However, the blood flow to the gastric mucosa adjacent to the anastomosis may be
      decreased. This suggests a possible redistribution of gastric blood flow to
      supply the anastomosis. If prolonged, this may contribute to poor anastomotic
      healing. L-Arginine infusion had no effect on blood flow at the anastomosis.

PMID- 10084680
TI  - Weaver cerebellar granule neurons show altered expression of NMDA receptor
      subunits both in vivo and in vitro.
AB  - Biochemical, immunocytochemical, and molecular biological techniques were used to
      investigate the expression of N-methyl-D-aspartate (NMDA) receptor subunits in
      migration-deficient weaver mouse cerebellum in vivo and in primary cultures of
      the vermal weaver granule neurons with or without a rescue by verapamil. We found
      that both NMDAR1(zeta1) message and protein were expressed by the weaver granule
      neurons in situ. Immunocytochemical and biochemical analyses indicated that
      granule neurons of the weaver cerebellum expressed R1(zeta1) and R2A(epsilon1)
      subunits but showed little expression of the R2B(epsilon2) subunit. In weaver
      cerebellum, the R2B(epsilon2) subunit was primarily expressed in nerve fibers of
      the internal granule cell layer and white matter. Reverse-transcriptase
      polymerase chain reaction followed by sequence analysis of the R1(zeta1) subunit
      indicated that the zeta1 subunit amplicons of both normal and weaver cerebella
      were identical, and that splice variants with exon 22 (1-2) and with or without
      exon 5 (a/b) or exon 21 (1-4) were detectable. The R2A(epsilon1), and
      R2B(epsilon2) subunits of the normal and weaver mouse cerebellum revealed no
      primary structural differences between the normal and weaver NMDA receptor
      subunits or the cloned mouse NMDA receptor subunits. In vermal cultures, normal
      granule neurons expressed all three NMDA receptor subunits (zeta1, epsilon1, and
      epsilon2), whereas the weaver neurons failed to express the epsilon2 subunit.
      Rescue of the weaver neurons by verapamil induced expression of the epsilon2
      protein along the granule neuronal surfaces. The present results suggest that
      lack of the epsilon2 subunit in the weaver cerebellum may relate to the lack of
      functional NMDA receptors and/or to the migratory failure of the weaver granule
      neurons. Our data further suggest that NMDA receptor-mediated neurotoxicity is an
      unlikely mediator of neuronal death of the weaver granule neurons. In fact, down
      regulation of the NMDA receptor expression and function may be a protective
      measure of the weaver granule neurons to reduce calcium entry via these
      receptors.

PMID- 10084681
TI  - Genetic and hormonal regulation of the death of peptidergic neurons in the
      Drosophila central nervous system.
AB  - To understand the role apoptosis plays in nervous system development and to gain
      insight into the mechanisms by which steroid hormones regulate neuronal
      apoptosis, we investigated the death of a set of peptidergic neurons in the CNS
      of the fruitfly Drosophila melanogaster. Typically, apoptosis in Drosophila is
      induced by the expression of the genes reaper, grim, or head involution defective
      (hid). We provide genetic evidence that the death of these neurons requires
      reaper and grim gene function. Consistent with this genetic analysis, we
      demonstrate that these doomed neurons accumulate reaper and grim transcripts
      prior to the onset of apoptosis. These neurons also accumulate low levels of hid,
      although the genetic analysis suggests that hid may not play a major role in the
      induction of apoptosis in these neurons. We show that the death of these neurons
      is dependent upon the fall in the titer of the steroid hormone 20-hydroxyecdysone
      that occurs at the end of metamorphosis, and demonstrate that the accumulation of
      both reaper and grim transcripts is inhibited by this steroid hormone. These
      observations support the notion that 20E controls apoptosis by regulating the
      expression of genes that induce apoptosis.

PMID- 10084682
TI  - A role for inwardly rectifying K+ channels in differentiation of NG108-15
      neuroblastoma x glioma cells.
AB  - The whole-cell patch-clamp technique was used to assess the current carried by
      inwardly rectifying K+ channels (K(ir)) and the resting membrane potential (RMP)
      during long-term culture of NG108-15 cells. Culture of this cell line in serum
      free medium triggers differentiation of a type I, neuron-like cell type followed
      by an eventual predominance of a type II, proliferative cell type. NG108-15 K(ir)
      currents, which strongly resemble currents carried by human ether-a-go-go related
      gene (HERG) K+ channels, exhibited significantly smaller current density for the
      more depolarized undifferentiated cells in growth media (GM) and type II cells
      compared to the neuron-like type I cells. Detailed examination of the transition
      from undifferentiated GM cells to type I cells revealed a shift in the voltage
      dependence of K(ir) activation which paralleled the more hyperpolarized RMP,
      neurite outgrowth, and biochemical differentiation characteristic of type I
      cells. Reverse-transcription polymerase chain reaction experiments using primers
      for the rat variant of HERG, RERG, revealed a a nearly twofold increase in RERG
      mRNA as cells differentiate from GM to type I, a finding entirely consistent with
      the increased K(ir) current density derived from patch-clamp recordings.
      Administration of CsCl(5 mM) blocked K(ir) currents and depolarized the RMP of
      type I cells. Furthermore, culture of NG108-15 cells in serum-free medium but
      with CsCl added significantly prevented neurite extension, an effect which was
      entirely reversible upon subsequent removal of CsCl. In contrast, other K+
      channel inhibitors (4-aminopyridine and tetraethylammonium), at concentrations
      without marked effects on K(ir), failed to affect neurite extension. These
      results suggest an important role of the K(ir) channels in determining the RMP
      and triggering morphological differentiation of the cell line.

PMID- 10084683
TI  - Early development of the motor and premotor circuitry of a sexually dimorphic
      vocal pathway in a teleost fish.
AB  - The plainfin midshipman fish (Porichthys notatus) has a caudal hindbrain vocal
      motor circuit that has been proposed to share a common embryonic origin with the
      hindbrain vocal networks of other vertebrates. In midshipman, this vocal circuit
      includes three groups of neurons: sonic motor, pacemaker, and ventral medullary.
      Here, transneuronal transport of biocytin or neurobiotin was used to delineate
      the early ontogeny of the three hindbrain vocal nuclei and their pattern of
      connectivity. The organization of the vocal nuclei was studied in animals
      beginning soon after hatching until the nuclei have the adult phenotype at the
      time fish become free-swimming. There is a clear sequence of events whereby
      motoneurons establish their connections with the sonic muscle prior to
      establishing connections with premotor neurons; developmental milestones of the
      vocal pathway parallel those of the sonic muscle. The results also indicate that
      sexual differentiation of the vocal motor system in midshipman begins early in
      development, well before any evidence of sexual maturation. Embryonic males and
      females differ in the relationship between soma size and body length for the
      three hindbrain nuclei. Males are also more variable than females in body mass,
      volume of the sonic motor nucleus, and motoneuron cell size.

PMID- 10084684
TI  - Neurogenesis of galanin cells in the bed nucleus of the stria terminalis and
      centromedial amygdala in rats: a model for sexual differentiation of neuronal
      phenotype.
AB  - Male rats possess twice as many cells that express arginine-vasopressin (AVP) in
      the bed nucleus of the stria terminalis (BST) and centromedial amygdala (CMA) as
      do females. This sex difference may arise from sex differences in the induction
      of AVP expression in galanin (GAL)-expressing cells, which themselves do not
      differ in number between males and females. To test whether AVP expression could
      arise from a single pool of galaninergic cells, we determined whether the cell
      birth profile of GAL-immunoreactive (ir) cells was similar to that of AVP-ir
      cells. Dams were injected with the cell birth marker bromodeoxyuridine (BrdU) on
      one of seven gestational dates, ranging from embryonic day 11 (E11) to E17. The
      resulting offspring were sacrificed at 3 months of age. Processing their brains
      for the presence of either GAL and BrdU, or AVP and BrdU immunoreactivity
      revealed that in both the BST and CMA, the majority of GAL-ir and AVP-ir cells
      were labeled with BrdU on E12 and E13. In contrast, most other cells in the same
      region were labeled on E14 and E15. The similarity in the timing of cell birth of
      the GAL-ir and AVP-ir cells is consistent with the idea that GAL-ir cells in the
      BST/CMA constitute a single pool of cells that may be induced to express AVP
      during development.

PMID- 10084685
TI  - Localization and regulation of basic fibroblast growth factor (FGF-2) and FGF
      receptor-1 in rat superior cervical ganglion after axotomy.
AB  - In response to peripheral nerve lesion, synthesis of basic fibroblast growth
      factor (FGF-2) increases in sensory ganglia and motoneurons. Here, we
      investigated the axotomy-induced regulation of FGF-2 and FGF receptor-1 (FGFR-1)
      expression in the autonomic nervous system using the sympathetic superior
      cervical ganglion of the adult rat as a model. Transcripts for both proteins were
      detected by ribonuclease protection assay. Western blotting indicated the
      presence of all three FGF-2 isoforms (18, 21, and 23 kD) in the superior cervical
      ganglion. Immunohistochemical analysis revealed FGF-2 localization in nuclei of
      satellite cells surrounding postganglionic perikarya. After transection of the
      carotid nerves, the number of FGF-2-immunoreactive glial cells increased. FGF-2
      mRNA was up-regulated within 6 h and remained elevated for 3 weeks. The 18-, 21-,
      and 23-kD isoforms were all increased 7 days after axotomy. FGFR-1
      immunoreactivity was observed in neuronal and nonneuronal nuclei in the normal
      rat superior cervical ganglion. In contrast to FGF-2, expression of FGFR-1 was
      unchanged in ganglia after axotomy. Taken together, the present results suggest
      that FGF-2 participates in neuron-glial interactions of sympathetic ganglia and
      may be involved in sympathetic neuron survival or nerve regeneration after nerve
      lesion.

PMID- 10084686
TI  - Cell type-specific regulatory sequences control expression of the Drosophila FMRF
      NH2 neuropeptide gene.
AB  - The FMRFamide (dFMRFa) neuropeptide gene is expressed in about 17 diverse cell
      types in the Drosophila central nervous system. This expression pattern is
      generated by transcriptional control elements that are distributed over 8
      kilobases of dFMRFa DNA. Previous studies identified one enhancer within the
      dFMRFa 5' region that is both necessary and sufficient to drive reporter
      transgene expression in one of the 17 dFMRFa cell types, the OL2 neurons. We now
      report the presence of two additional, non-overlapping enhancers within the gene:
      One drives expression by the six Tv neuroendocrine cells, and another in the four
      X and X2 interneurons. We also show that the Tv neuron-specific enhancer itself
      has complex organization, with several positively and negatively acting cis
      elements. Together, these results describe the organization of what is likely to
      be a prototypic neuronal gene promoter: an assemblage of multiple, independent,
      cell type-specific enhancers, each consisting of multiple quantitative elements.

PMID- 10084687
TI  - Axons of olfactory receptor cells of transsexually grafted antennae induce
      development of sexually dimorphic glomeruli in Manduca sexta.
AB  - The influence of olfactory receptor cell (ORC) axons from transsexually grafted
      antennae on the development of glomeruli in the antennal lobes (ALs), the primary
      olfactory centers, was studied in the moth Manduca sexta. Normally during
      metamorphic adult development, the pheromone-specific macroglomerular complex
      (MGC) forms only in the ALs of males, whereas two lateral female-specific
      glomeruli (LFGs) develop exclusively in females. A female AL innervated by ORC
      axons from a grafted male antenna developed an MGC with three glomeruli, like the
      MGC of a normal male AL. Conversely, a male AL innervated by ORC axons from a
      grafted female antenna lacked the MGC but exhibited LFGs. ORC axons from grafted
      male antenna terminated in the MGC-specific target area, even in cases when the
      antennal nerve (AN) entered the AL via an abnormal route. Within ectopic neuromas
      formed by ANs that had become misrouted and failed to enter the brain, male
      specific axons were not organized and formed terminal branches in many areas. The
      results suggest the presence of guidance cues within the AL for male-specific ORC
      axons. Depending on the sex of the antennal innervation, glial borders formed in
      a pattern characteristic of the MGC or LFGs. The sex-specific number of
      projection neurons (PNs) in the medial group of AL neurons remained unaffected by
      the antennal graft, but significant changes occurred in the organization of PN
      arborizations. In gynandromorphic females, LFG-specific PNs extended processes
      into the induced MGC, whereas in gynandromorphic males, PNs became restricted to
      the LFGs. The results indicate that male-and female-specific ORC axons play
      important roles in determining the position, anatomical features, and innervation
      of sexually dimorphic glomeruli.

PMID- 10084688
TI  - NCAM stimulates the Ras-MAPK pathway and CREB phosphorylation in neuronal cells.
AB  - The neural cell adhesion molecule NCAM plays an important role in axonal growth,
      learning, and memory. A signaling pathway has been elucidated in which clustering
      of the NCAM140 isoform in the neural plasma membrane stimulated the activating
      phosphorylation of mitogen-activated protein kinases (MAPKs) and the
      transcription factor cyclic AMP response-element binding protein (CREB). NCAM
      clustering transiently induced dual phosphorylation (activation) of the MAPKs
      ERK1 and ERK2 (extracellular signal-regulated kinases) by a pathway regulated by
      the focal adhesion kinase p125fak, p59fyn, Ras, and MAPK kinase. CREB
      phosphorylation at serine 133 induced by NCAM was dependent in part on an intact
      MAPK pathway. c-Jun N-terminal kinase, which is associated with apoptosis and
      cellular stress, was not activated by NCAM. Inhibition of the MAPK pathway in rat
      cerebellar neuron cultures selectively reduced NCAM-stimulated neurite outgrowth.
      These results define an NCAM signal transduction mechanism with the potential for
      modulating the expression of genes needed for axonal growth, survival, and
      synaptic plasticity.

PMID- 10084689
TI  - Immature granule neurons from cerebella of different ages exhibit distinct
      developmental potentials.
AB  - Cultured cerebellar granule neurons exhibit different developmental potentials in
      culture dependent on cerebellar age at plating. In cultures prepared at postnatal
      days (P)2-6, when all granule neurons reside in the external germinal layer (EGL)
      in vivo, levels of the GABA(A) receptor beta2 and gamma2 subunit mRNAs are
      constant. In contrast, in cultures prepared at P8-10, when neurons have begun to
      migrate into the internal granule cell layer (IGL), the mRNAs increase several
      fold in a pattern mimicking that found in vivo. To determine the relationship
      between neuronal differentiation in culture and potential to express GABA(A)
      receptor beta2 and gamma2 subunit transcripts in the mature pattern, neuronal
      maturity in P6 and P10 cultures was compared. Bromodeoxyuridine labeling studies
      demonstrated that P10 as well as P6 cultures contained neurons only from the EGL.
      Moreover, the maturation of cultured P10 and P6 neurons appeared virtually
      identical. Cells dissociated at both ages expressed mRNAs encoding the EGL
      markers MATH-1 and TAG-1. The MATH-1 transcript disappeared from cultures
      maintained 4 days when expression of the GABA(A) receptor alpha6 subunit, a
      marker of mature cells, was initiated. Thus, although cultured P6 and P10 granule
      neurons exhibit the same maturation markers, P10 neurons presumably have been
      modulated by environmental cues specifying increases in GABA(A) receptor beta2
      and gamma2 subunit expression. This possibility is supported by the finding that
      extracts of dissociated P10 cells but not P6 cells induce increases in GABA(A)
      receptor subunit expression in P6 cultures.

PMID- 10084690
TI  - Prevention of thrombin-induced motoneuron degeneration with different
      neurotrophic factors in highly enriched cultures.
AB  - Previous reports have shown that neuronal and glial cells express functionally
      active thrombin receptors. The thrombin receptor (PAR-1), a member of a growing
      family of protease activated receptors (PARs), requires cleavage of the
      extracellular amino-terminus domain by thrombin to induce signal transduction.
      Studies from our laboratory have shown that PAR-1 activation following the
      addition of thrombin or a synthetic thrombin receptor activating peptide (TRAP)
      induces motoneuron cell death both in vitro and in vivo. In addition to
      increasing motoneuron cell death, PAR- 1 activation leads to decreases in the
      mean neurite length and side branching in highly enriched motoneuron cultures. It
      has been suggested that motoneuron survival depends on access to sufficient
      target-derived neurotrophic factors through axonal branching and synaptic
      contacts. However, whether the thrombininduced effects on motoneurons can be
      prevented by neurotrophic factors is still unknown. Using highly enriched avian
      motoneuron cultures, we show here that alone, soluble chick skeletal muscle
      extracts (CMX), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic
      factor (CNTF), and glial cell line-derived neurotrophic factor (GDNF)
      significantly increased motoneuron survival compared to controls, whereas nerve
      growth factor (NGF) did not have a significant effect on motoneuron survival.
      Furthermore, cotreatment with muscle-derived agents (i.e., CMX, BDNF, GDNF)
      significantly prevented the death of motoneurons induced by alpha-thrombin. Yet,
      non-muscle-derived agents (CNTF and NGF) had little or no significant effect in
      reversing thrombin-induced motoneuron death. CMX and CNTF significantly increased
      the mean length of neurites, whereas NGF, BDNF, and GDNF failed to enhance
      neurite outgrowth compared to controls. Furthermore, CMX and CNTF significantly
      prevented thrombin-induced inhibition of neurite outgrowth, whereas BDNF and GDNF
      only partially reversed thrombin-induced inhibition of neurite outgrowth. These
      findings show differential effects of neurotrophic factors on thrombin-induced
      motoneuron degeneration and suggest specific overlaps between the trophic and
      stress pathways activated by some neurotrophic agents and thrombin, respectively.

PMID- 10084691
TI  - Cloning and characterization of AASPs: novel axon-associated SH3 binding-like
      proteins.
AB  - Two cDNAs encoding closely related proteins were isolated from a crayfish nervous
      system lambdagtl0 cDNA library with a rat synapsin Ia cDNA probe. These proteins
      were expressed exclusively in neurons, were highly enriched in axons of the
      crayfish, and contained multiple, overlapping, putative Src homology 3 (SH3)
      binding sites. In concert with other proteins containing Src homology domains,
      SH3 binding proteins are thought to mediate protein-protein interactions in
      receptor signaling processes and with the cytoskeleton. We have named these
      proteins axon-associated SH3 binding-like proteins (AASPs). Except for these SH3
      binding regions, which are also found in synapsins, AASPs were unlike any
      proteins in the database. AASPs were differentially expressed among motoneuron
      populations in crayfish and were found in growing axons and growth cones in
      culture. Affinity purified polyclonal antibodies to AASP-168 recognized
      immunoreactive proteins in rat and Xenopus, suggesting that AASPs may be
      conserved across species. Although the cellular function of AASPs is unclear at
      this time, they appear to be novel members of a neuron-specific SH3 binding
      protein family, which includes the synapsins.

PMID- 10084692
TI  - Monomorphic HLA class I-(non-A, non-B) expression on Ewing's tumor cell lines,
      modulation by TNF-alpha and IFN-gamma.
AB  - In this study, the expression of polymorphic and non-polymorphic MHC antigens in
      Ewing's tumor (ET) cells was examined by surface staining, Western blots and
      transcriptional analysis. Cell lines derived from Ewing's tumors largely lack
      polymorphic HLA class Ia antigens of both the HLA-A and the HLA-B loci but
      binding of monomorphic HLA antibodies indicates significant expression of HLA-C
      locus antigens and/or HLA class Ib molecules. HLA Ib molecules encoded by the HLA
      E, -F or -G loci with a molecular mass of less than 44 kDa were not detected in
      lysates of either constitutive or TNF-alpha plus IFN-gamma treated ET cells. Two
      representative ET cell lines with either detectable HLA-A, -B antigens (A673) or
      absolutely non-detectable HLA-A, -B antigens (SK-ES-1) were further subjected to
      transcriptional analysis. A673 mRNA hybridized with HLA-A, -B, -C and HLA-E
      specific probes in Northern blots. By contrast, mRNA specific for HLA-A, -B, -C
      was negative in SK-ES-1 but TNF-alpha plus IFN-gamma reconstituted HLA-A, -B, -C
      transcription in this cell line. HLA-E was transcribed in A673 but not in SK-ES
      1. Combining mRNA and surface expression of HLA class Ia molecules results in a
      highly variable pattern of defective HLA class I expression in this type of
      neuroectodermal tumor. The involvement of the ET-specific fusion transcript
      EWS/Fli-1 in modulating the HLA-A and -B locus antigens is likely to occur by the
      upregulation of c-myc in these tumors. The exceptionally constant expression of
      HLA-C or some other non-A, non-B antigens (reactive with defined monoclonal
      antibodies) implies important consequences on tumor-cell resistance against
      specific CTL and NK activity in vivo.

PMID- 10084693
TI  - Enhancement of mucosal immune responses to the influenza virus HA protein by
      alternative approaches to DNA immunization.
AB  - DNA immunization provides many advantages as an approach to prevent infectious
      diseases. However, although previous studies using this approach have
      demonstrated immune responses in serum, they were not successful in inducing
      significant levels of antibodies in secretions. In this study, plasmid DNAs
      expressing the influenza virus hemagglutinin glycoprotein have been evaluated for
      their ability to induce antibody responses in serum and saliva when used alone or
      along with either liposomes or bioadhesive polymers as mucosal delivery vehicles.
      Significant levels of virus-specific Ig in serum as well as secretory IgA in
      saliva were detected in mice following mucosal DNA immunization. These antibodies
      were found to block the infectivity of the virus using a plaque reduction assay.
      Our findings thus indicate that mucosal DNA immunization with specific delivery
      systems can elicit virus-specific antibody responses in serum as well as IgA
      responses at mucosal surfaces.

PMID- 10084694
TI  - The development of a bi-specific anti-CD161A x anti-tumor antibody for rat NK
      cell targeting.
AB  - In order to improve the therapeutic efficacy of adoptive immunotherapy of cancer
      using IL-2-activated NK (A-NK) cells, we developed a bi-specific monoclonal
      antibody (BimAb) 3.2.3xCC52. One specificity of the BimAb (mAb 3.2.3) was
      directed against rat CD161A (NKR-P1A) which has been shown to be an activation
      structure on rat NK cells involved in lysis of target cells and cytokine
      secretion. The other specificity (mAb CC52) was directed against a tumor
      associated antigen on the rat colon adenocarcinoma cell line CC531. The
      hybridomas producing 3.2.3 and CC52 were fused, resulting in a quadroma producing
      the desired 3.2.3xCC52 BimAb. The hybridomas produced antibodies of different
      isotypes (IgG2b and IgG1 respectively) which enabled us to pre-select quadromas
      with a high likelihood for production of BimAb, through testing for the
      production of bi-isotypic antibodies. Production of functional BimAb by the
      selected quadromas was demonstrated in an assay showing enhanced conjugate
      formation between CD161A+ cells and CC531 tumor cells. We also tested the
      3.2.3xCC52 BimAb for its capacity to enhance NK cell-mediated lysis of CC531
      tumor cells in 4 h and 19 h 51Cr release assays; in a prolonged (2 day) tumor
      neutralization assay using a tetrazolium salt (MTT)-based assay; and in tests for
      apoptosis using Annexin V-FITC. Although this BimAb was not demonstrated to cause
      enhanced lysis of CC531 cells by CD161A+ effector cells in vitro, it might be a
      useful tool to enhance the number of NK cells at the tumor site and/or prolong
      contact between tumor cells and NK cells in vivo, thereby probably enhancing the
      therapeutic efficacy of NK cells.

PMID- 10084695
TI  - A novel 26 kilodalton antigen expressed on the surface membrane of activated T
      cells.
AB  - We have identified and characterized the tissue distribution of the antigen
      recognized by a novel monoclonal antibody (mAb) 1B10, raised against an activated
      gammadelta T cell clone. Immunohistochemistry of tissue sections, and analysis of
      single cell suspensions by flow cytometry revealed that mAb 1B10 weakly reacted
      with <6% of normal human peripheral blood mononuclear cells (PBMC). After 5-6
      days of in vitro culture of PBMC activated with phytohemagglutinin (PHA), 55% of
      the CD4+ and 25% of the CD8+ T cells became 1B10+. 1B10 expression was maintained
      on long term cultured interleukin 2 (IL-2)-dependent T cell receptor (TCR)
      alphabeta+ and gammadelta+ clones, and importantly, in contrast to resting T
      cells, the majority of in vivo activated synovial T lymphocytes from a patient
      with rheumatoid arthritis were 1B10+. In addition, myelo-monocytic U927 cells,
      tissue macrophages and some epithelia and fibroblasts were found to react with
      mAb 1B10. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of
      molecules immuno-precipitated by mAb 1B10 from radio-iodinated cell surface
      membrane lysates of T lymphocyte and U937 cells revealed 26 and 29 kiloDalton
      (kDa) glycoproteins respectively. In conclusion, mAb 1B10 recognizes a novel
      <<late>> appearing 26 kDa T cell activation antigen that may be useful for
      further studies of activated T cells in health and disease.

PMID- 10084696
TI  - In vitro differentiation and characterization of human peritoneal macrophages
      from CAPD-peritonitis patients.
AB  - Studies on human macrophages are restricted due to difficulties in isolating
      significant numbers of human macrophages. High numbers of monocytes/macrophages
      can be obtained from peritonitis effluents of patients treated with peritoneal
      dialysis. To determine whether these cells might be useful for functional
      studies, we characterized peritoneal macrophages (PM) immediately after isolation
      from the dialysate effluents and their subsequent differentiation. During a 10
      days culture period they differentiated morphologically and phenotypically (FACS
      analysis) from monocyte-like cells to macrophages. Reflecting the intraperitoneal
      inflammation we found protein- and mRNA-synthesis of IL-8 and monocyte
      chemoattractant-protein-1 (MCP-1) to be upregulated in PM after isolation from
      the effluents. In contrast, TNF-alpha was downregulated and could not be
      stimulated by LPS and/or IFN-gamma, reflecting the phenomenon of desensitization.
      After 10 days in culture, cytokine production normalized to a constitutive level
      and the TNF-alpha responsiveness to LPS was restored. These data suggest the
      recovery of PM from the inflammatory prestimulation. Therefore PM harvested from
      peritoneal dialysis effluents might provide a useful tool for further studies on
      the role of human macrophages in inflammation.

PMID- 10084697
TI  - Reduced catecholamine response of lymphocytes from patients with rheumatoid
      arthritis.
AB  - Catecholamines modulate lymphocyte function via stimulation of beta2-adrenergic
      receptors (beta2R). Previous investigations revealed a decreased density of
      beta2R on peripheral blood mononuclear cells (PBMC) in patients with chronic
      rheumatic diseases. Aim of the present study was to determine the impact of this
      decrease on catecholamine response of PBMC from patients with rheumatoid
      arthritis (RA) in vitro. PBMC from 17 patients with RA and 12 healthy blood
      donors (HD) were investigated. Beta2R were determined by a radioligand binding
      assay. The effects of epinephrine (E) and norepinephrine (NE) on PBMC
      proliferation were studied using cells activated with pokeweed mitogen (PWM) and
      monoclonal anti-CD3-antibodies (OKT3), respectively. In parallel, alpha1- or beta
      receptor antagonist were added to the culture to determine the specificity of the
      catecholaminergic effects. The results showed that depending on the stimulus and
      the catecholamine concentration employed E and NE exert inhibitory (OKT3) or
      stimulatory signals (PWM) on lymphocyte proliferation. Inhibitory effects could
      be abolished by adding beta-antagonist, while stimulatory signals were diminished
      after addition of alpha1- of beta-antagonist. Patients with RA showed a
      significantly reduced density of beta2R compared to HD paralleled by a
      significantly reduced influence of catecholamines on lymphocyte function. The
      study demonstrates the intricate relationship between PBMC reactivity and
      catecholamine effects that are mediated via alpha1- and beta-adrenergic
      receptors. In this respect the reduced catecholamine response of PBMC from RA
      patients may contribute to the pathogenic process of RA.

PMID- 10084698
TI  - C3 molecules internalize and enhance the growth of Lewis lung carcinoma cells.
AB  - C3 molecules from normal murine serum are mainly bound to Lewis lung carcinoma
      cells (3LL) that do not express CRs, mainly through covalent binding as
      determined by the appearance of bands stained with anti-C3 and larger than 190 kD
      in immunoblots of proteins in whole cell extracts. Methylamine-treated, or
      zymosan-treated normal mouse serum, heat inactivated, or EDTA-treated murine
      serum resulted in low C3 deposition on 3LL cells, as indicated by fluorescence
      tests and immunoblotting. Cytofluorimetric studies showed that C3 molecules bound
      to 3LL cells were internalized in a time- and temperature-dependent process. This
      was confirmed by electronmicroscopic studies. The conditions allowing C3 fixation
      to acceptor sites and subsequent internalization increased cell proliferation.
      This was also true, when serum from mice genetically deficient in C5 was used
      which stresses the role of C3 in contrast to effects of membrane attack complex
      formation.

PMID- 10084699
TI  - Immunostimulatory properties of genomic DNA from different bacterial species.
AB  - Bacterial DNA has potent immunological properties because of its content of
      immunostimulatory sequences centering on CpG motifs. To investigate whether DNA
      from various bacterial species differ in these properties, the activity of a
      panel of DNA was assessed in in vitro cultures of murine spleen cells. This panel
      varied in base composition and included DNA from Clostridium perfringens (CP),
      Escherichia coli (EC), Micrococcus lysodeikticus (MC), Staphylococcus aureus
      (SA), and, as a mammalian DNA control, calf thymus (CT) DNA. In assays of IL-12
      and IFN-gamma production as well as B cell mitogenesis, these DNA showed marked
      differences in their immunostimulatory activity. For both cytokine and B cell
      responses, EC DNA demonstrated the highest activity while CP DNA had the lowest
      activity among the bacterial DNA. To determine whether differences in stimulatory
      capacity resulted from differences in cell uptake, the activity of DNA complexed
      with lipofectin was tested. While the addition of lipofectin to DNA increased
      stimulation by all DNA, it did not change the relative potency of the DNA tested.
      These results indicate that bacterial DNA differ in their immunostimulatory
      capacity, most likely reflecting their content of CpG motifs. These differences
      could affect the induction of innate immunity as well as the consequences of
      infection.

PMID- 10084700
TI  - Effect of fetal calf serum on cytokine release by bone marrow-derived macrophages
      during infection with intracellular bacteria.
AB  - Bone marrow-derived macrophages (BMM) comprise a population of quiescent cells
      which can be activated by defined signals. Here, we directly compare the release
      of chemokines and monokines by BMM raised either in serum-supplemented or in
      serum-free medium in response to Listeria monocytogenes EGD or Mycobacterium
      bovis BCG infection. We focused on this issue because there have been several
      controversial reports on the production of cytokines by BMM due to different in
      vitro culture conditions. Culture in serum-supplemented medium primed BMM for
      release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL
      12, but had no effect on macrophage inflammatory protein (MIP)-1alpha and tumor
      necrosis factor (TNF)-alpha production in response to L. monocytogenes infection.
      After challenge infection with M. bovis, BMM raised and stimulated in serum
      supplemented medium secreted higher levels of MCP-1, MIP-1alpha, IL-6, and TNF
      alpha but not of IL-12 as compared to BMM cultured and infected in a serum-free
      medium. The effects of serum could be partially mimicked by interferon-gamma.
      Because the serum components responsible for BMM priming are undefined, BMM
      cultured under serum-free conditions provide an appropriate cell population for
      defining macrophage activating signals.

PMID- 10084701
TI  - Autocrine transforming growth factor-beta from chronic lymphocytic leukemia-B
      cells interferes with proliferative T cell signals.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of
      noncycling B cells in lymphatic and extralymphatic tissues. In the present study
      we investigated the possible contribution of TGF-beta, as secreted by CLL-B
      cells, on this low proliferative state. CLL-B cells were shown to express TGF
      beta RNA and to release bioactive TGF-beta into culture supernatants. Antibody
      neutralization of endogenously secreted TGF-beta increased the proliferation of
      CLL-B cells as cultured in the presence of IL-2 or IL-4 or in direct contact with
      activated CD4+ T cells. In these culture systems, addition of exogenous TGF-beta
      downregulated basal and cytokineinduced proliferation of CLL-B cells. In
      contrast, neither neutralization of endogeneous TGF-beta, nor addition of
      exogeneous TGF-beta changed the proliferation of CLL-B cells as cultured in the
      CD40 system. In order to further explore this differential antiproliferative
      effect of TGF-beta, cytokine secretion of B cells and of CD4+ T cells as well as
      surface marker expression of CD4+ T cells were assessed in relation to TGF-beta:
      There was no negative effect of TGF-beta on autocrine secretion of TNF-alpha or
      sCD23 by CLL-B cells. Unlike tonsillar B cells, CLL-B cells cultured alone or in
      the CD40 system did no release significant amounts of IL-6 or IL-8 into
      supernatants. Secretion of IL-2 or IL-4 by activated CD4+ T cells was higher,
      when T cells were cocultured with normal tonsillar B cells than with CLL-B cells.
      The amount of IL-2 or IL-4 released by CD4+ T cells cocultured in direct contact
      with tonsillar or CLL-B cells was not consistently influenced either by
      neutralization of endogenous TGF-beta or by addition of TGF-beta. Exogenous TGF
      beta did not downregulate expression of CD40L, CD27, CD28, CD54 or mTNF-alpha by
      T helper cells activated with anti-CD3 or PHA. In conclusion, autocrine secretion
      of TGF-beta exhibits an antiproliferative effect on CLL-B cells. This effect is
      most relevant in B cells cultured in direct contact with activated CD4+ T cells
      suggesting an indirect mode of action.

PMID- 10084702
TI  - Ubiquitin-like polypeptide inhibits the proliferative response of T cells in
      vivo.
AB  - The monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by
      murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressive
      functions. Recently, we demonstrated that the recombinant form of the ubiquitin
      like segment (rUbi-L) of MNSFbeta, a 15.6 kDa-protein consisting of a polypeptide
      with 36% homology with ubiquitin fused to the ribosomal protein S30, presented an
      antigen-nonspecific immunoregulatory action in a manner similar to native MNSF.
      Although this cytokine has been characterized in vitro, little is known about its
      effects in vivo. Thus, we investigated whether rUbi-L shows a suppressor activity
      in vivo. The proliferative response of Con A (5 microg/ml)-stimulated splenocytes
      of mice treated with rUbi-L (500 ng/body) was notably decreased in a dose
      dependent manner (max. 57+/-20%). In contrast, administration of high dose
      ubiquitin (50 microg/body) showed a little, but significant, effect (30+/-7%).
      Interestingly, concomitant addition of ubiquitin inhibited Ubi-L-induced
      suppression. Mice injected with rUbi-L without gelatin did not show any
      suppressive effect. NA4 (1microg/body), a neutralizing monoclonal antibody
      against rUbi-L, abolished the Ubi-L-mediated suppression. Therefore, ubiquitin
      like polypeptide may be implicated in the immune responses in vivo.

PMID- 10084703
TI  - Apparent trans-chromosomal antibody class switch in mice bearing an Igh(a) mu
      chain transgene on an Igh(b) genetic background.
AB  - Native high molecular weight dextran induces a thymus-independent response in
      BALB/c mice. When the dextran epitope is linked to a protein carrier the response
      becomes thymus-dependent. IgG antibodies produced after secondary immunization
      had epitope specificity and idiotope of myeloma M104E. The antibody of M104E (mu,
      lambda1) is representative for antibodies produced by mice with immunoglobulin
      haplotype Igh(a) in response to immunization with dextran B1355S. Myeloma product
      and physiological antibodies share specificity for the alpha(1-3) glucosidic
      linkage and have idiotopes in common. Mice with haplotypes other than Igh(a)
      (e.g. Igh(b)) are unable to yield this type of response. A complete rearranged
      immunoglobulin mu-chain gene with a VDJ-region from BALB/c (Igh(a)) myeloma
      protein M104E had been introduced into the genome of BALB/c congenic mice having
      the haplotype Igh(b). As was shown previously in our laboratory the M104E mu
      chain transgene confers Igh(a)-type reactivity to Igh(b) mice. In experiments
      described in this report we used the thymus-dependent form of the antigen to
      immunize mice bearing the M104E mu-chain, either alone or together with the
      lambda1-chain, as a transgene on an Igh(b) genetic background. Serological
      analysis revealed a class switch to IgG very similar to that seen in BALB/c mice
      with respect to magnitude, kinetics, epitope and idiotope specificity. The
      pattern of IgG subclass expression was indistinguishable in mu-chain transgenic
      Igh(b) and normal BALB/c mice. The class switch occurred even though, as is shown
      here, the transgene had become incorporated in a site not linked to the Igh locus
      on chromosome 12. We propose a model for this apparent trans-chromosomal class
      switch recombination which is based on mechanisms known for conventional switch
      recombination.

PMID- 10084704
TI  - Electrophysiological and morphological properties of neurons in the ventral horn
      of the turtle spinal cord.
AB  - In this report, we present recent findings on the electrophysiological and
      morphological properties of spinal motoneurons (MNs) and interneurons (INs) of
      the adult turtle which were studied in slices of the spinal cord. The range of
      values for the measured electrophysiological parameters in 96 tested cells
      included: resting potential, -57 to -83 mV; input resistance, 2.5-344 M omega;
      time constant, 2.5-63 ms; rheobase current, 0.04-5.3 nA; after-hyperpolarization
      (AHP) duration, 72-426 ms; AHP half-decay time; 11-212 ms; and, slope of the
      stimulus current-spike frequency relationship, 3.4-235 Hz/nA. For another 20
      cells, we made both morphological and electrophysiological measurements (the
      latter values within the above ranges). Their ranges in morphological properties
      included: soma diameter, 20-54 microm; soma surface area, 299-2045 microm2; soma
      volume, 2.3-45 microm3 x 10(4); rostro-caudal dendritic projection distance, 150
      1200 microm; and, sum of dendritic lengths, 1.5-16 microm x 10(3). The emphasized
      findings include: 1) the quality and robustness of the intracellular recordings,
      which enabled accurate measurement of the action potential's shape parameters
      (spike, afterhyperpolarization [AHP]); 2) the substantial AHP of the INs' AP; 3)
      no single action-potential shape parameter (nor combination of parameters) being
      cardinal for its (or their combined) changes matching the profile of the initial
      and later phases of spike-frequency adaptation; 4) the utility and flexibility of
      a cluster analysis (using varying combinations of passive, transitional and
      active cell properties) for providing a provisional classification of low (like
      cat S) and high (like cat F) threshold MNs, and groups of INs with non
      spontaneous versus spontaneous discharge; 5) the clear-cut morphological
      confirmation of the provisional classification strategy; 6) the basis for testing
      the possibility that one of the provisionally classified MN types innervates non
      twitch muscle fibers; and 7) the heuristic value of comparing the properties of
      MNs versus INs across vertebrate species, with an emphasis on the lamprey,
      turtle, and cat.

PMID- 10084705
TI  - Functional implications of dendritic voltage-dependent conductances.
AB  - Layer five pyramidal neurons of rat and cat neocortex have numerous ionic
      conductance mechanisms. The presence of these voltage-dependent conductances in
      the dendrites has a significant effect on the transmission of current from
      synaptic sites to the spike generating region in the proximal axon. Here we show
      such threshold activation of persistent sodium channels markedly amplifies
      current flowing through glutamate activated dendritic channels.

PMID- 10084706
TI  - Modulation of motoneuron N-methyl-D-aspartate receptors by the inhibitory
      neurotransmitter glycine.
AB  - Previous studies in the central nervous system have shown that glycine is a co
      agonist with glutamate at central N-methyl-D-aspartate receptors (NMDA-Rs).
      However, there is considerable controversy as to whether the glycine site on NMDA
      Rs is saturated. If this site were not saturated then glycine released from
      glycinergic synaptic terminals might 'spill-over' and activate NMDA-Rs. Since
      motoneurons have both NMDA and glycine synapses these neurons present an optimal
      substrate for testing whether the glycine binding site of NMDA-Rs is activated by
      transmitter released from glycine synaptic terminals. Using an in vitro brainstem
      slice preparation we report on initial experiments to investigate whether the
      glycine binding site of NMDA-Rs is saturated in motoneurons. Specifically, we
      investigated the question of whether the response of neonatal rat hypoglossal
      motoneurons (HMs) to a brief application of NMDA is enhanced by the presence of
      exogenous glycine. We found that exogenously applied glycine (1 mM) enhanced the
      NMDA activated membrane current. We conclude that in brainstem slices the glycine
      site at motoneuronal NMDA-Rs is not saturated, and that synaptically-released
      glycine may modulate NMDA-Rs mediated responses.

PMID- 10084707
TI  - Functional identification of the input-output transforms of mammalian
      motoneurones.
AB  - We studied the responses of rat hypoglossal and cat lumbar motoneurones to a
      variety of excitatory and inhibitory injected current transients during
      repetitive discharge. The amplitudes and time courses of the transients were
      comparable to those of the synaptic currents underlying postsynaptic potentials
      (PSPs) recorded in these cells. Poisson trains of these current transients were
      combined with an additional independent, high frequency random waveform to
      approximate band-limited white noise. The composite, white noise waveform was
      then superimposed on long duration suprathreshold current steps. We used the
      responses of the motoneurones to the white noise stimulus to derive zero-, first-
      and second-order Wiener kernels, which provide a quantitative description of the
      relation between injected current and discharge probability. The convolution
      integral computed for an injected current waveform and the first-order Wiener
      kernel provides the best linear prediction of the associated peristimulus time
      histogram (PSTH). This linear model provided good matches to most of the PSTHs
      compiled between the times of occurrence of individual current transients and
      motoneurone discharges. However, for the largest amplitude current transients, a
      significant improvement in the PSTH match was often achieved by expanding the
      model to include the convolution of the second-order Wiener kernel with the
      input. The overall transformation of current inputs into firing rate could be
      approximated by a second-order Wiener Model, i.e., a cascade of a dynamic, linear
      filter followed by a static non-linearity. At a given mean firing rate, the non
      linear component of the motoneurone's response could be described by the square
      of the linear component multiplied by a constant coefficient. The amplitude of
      the response of the linear component increased with the average firing rate,
      whereas the value of the multiplicative coefficient in the nonlinear component
      decreased. As a result, the overall transform could be predicted from the mean
      firing rate and the linear impulse response, yielding a relatively simple,
      general description of the motoneurone's input-output function.

PMID- 10084708
TI  - A comparison of human motoneuron data to simulated data using cat motoneuron
      models.
AB  - The response of repetitively firing human motoneurons to a composite excitatory
      input was evaluated. It was clearly shown that the response of the motoneurons to
      the transient input decreased with an increase in the background firing rate of
      the cell. The current model of repetitively firing human motoneurons could not
      account for this experimental result. Therefore, a compartmental modelling
      approach was used to simulate the repetitive firing properties of anaesthetised
      cat motoneurons under current clamp conditions. The modelled motoneurons were
      used in simulations similar to the experimental paradigms where the response to a
      composite excitatory input was evaluated at different background firing rates.
      The motoneuron models also showed a decrease in response to the excitatory input
      at faster background firing rates. The results suggest that human motoneurons are
      more comparable to motoneurons in the anaesthetised cat preparation than formerly
      thought. The results also demonstrate that the apparent efficacy of a synaptic
      input may be modulated by changes in background firing rate of the postsynaptic
      neuron.

PMID- 10084709
TI  - Studies of stimulus-evoked responses in single motoneurones in humans.
AB  - Surface electromyography (EMG) has been a powerful technique for studying reflex
      and other stimulus-evoked responses in the human nervous system. However,
      important additional insights can be gained into the operation of neural circuits
      by studying the responses of single motor units to various stimuli. In this
      paper, some of the advantages of single motor unit recording will be canvassed,
      and some examples of the application to this method to the study of reflex
      responses to sensory stimuli and brain stimulation will be presented.

PMID- 10084710
TI  - Synaptic integration in spinal motoneurones.
AB  - Spinal motoneurones receive thousands of presynaptic excitatory and inhibitory
      synaptic contacts distributed throughout their dendritic trees. Despite this
      extensive convergence, there have been very few studies of how synaptic inputs
      interact in mammalian motoneurones when they are activated concurrently. In the
      experiments reported here, we measured the effective synaptic currents and the
      changes in firing rate evoked in cat spinal motoneurones by concurrent repetitive
      activation of two separate sets of presynaptic neurons. We compared these effects
      to those predicted by a linear sum of the effects produced by activating each set
      of presynaptic neurons separately. We generally found that when two inputs were
      activated concurrently, both the effective synaptic currents and the synaptically
      evoked changes in firing rate they produced in motoneurones were generally
      linear, or slightly less than the linear sum of the effects produced by
      activating each input alone. The results suggest that the spatial distribution
      synaptic terminals on the dendritic trees of motoneurones may help isolate
      synapses from one another, minimizing non-linear interactions.

PMID- 10084711
TI  - Orderly recruitment among motoneurons supplying different muscles.
AB  - Virtually all movements involve the recruitment of motor units from multiple
      muscles. Given the functional diversity of motor units (motoneurons and the
      muscle fibers they supply), the effective production of specific movements
      undoubtedly depends upon some principle(s) to organize the ensemble of active
      motor units. The principle acting to organize the recruitment of motor units
      within muscles is the size principle, whereby the first motor units to be
      recruited have the smallest values for axonal conduction velocity and contractile
      force, and are the slowest to contract and fatigue. Here we consider the
      possibility that the size principle applies in the recruitment of motor units
      across muscles, i.e., that regardless of their muscles of origin, active motor
      units are recruited in rank order, for example, from low to high conduction
      velocity. The benefits of orderly recruitment across muscles could be similar to
      the acknowledged advantages of orderly recruitment within muscles. One benefit is
      that the neural process involved in organizing active motor units would be
      simplified. In a muscle-based scheme, the size principle would organize only
      those motor units within individual muscles, leaving the nervous system with the
      additional task of coordinating the relative activities of motor units from
      different muscles. By contrast, in an ensemble-based scheme, orderly recruitment
      of all motor units according to the size principle would automatically coordinate
      motor units both within and across motor nuclei. Another potential benefit is the
      provision for movements with smooth trajectory, the result of interleaving the
      divergent torque contributions made by motor units from muscles that differ in
      their orientations about joints. Otherwise, if order were restricted within
      muscles, the torque trajectory of a joint would change unevenly as participating
      muscles begin contracting at different times and grade activity at different
      rates. These considerations support speculation that motor units recruited from
      co-contracting muscles are collectively recruited according to the size
      principle.

PMID- 10084712
TI  - Discharge properties of motoneurones: how are they matched to the properties and
      use of their muscle units?
AB  - A general survey is given of old as well as more recent findings concerning
      matches between electrophysiological properties of motoneurones and contractile
      properties of their muscle fibres. Mechanisms for creating and maintaining such
      matches are discussed. It is pointed out that it is not sufficient to describe
      the variation of functional motoneurone characteristics simply in terms of 'fast'
      or 'slow': all properties seem continuously graded and there is cytochemical
      evidence for several, seemingly independent parameters of functional
      specialisation.

PMID- 10084713
TI  - The role of voltage-sensitive dendritic conductances in generating bistable
      firing patterns in motoneurons.
AB  - Motoneurons receive a dense innervation from fibers that descend from the
      brainstem and release the monoamines serotonin and noradrenalin. When monoamines
      are present, motoneurons can produce plateau potentials, which are sustained
      depolarizations that outlast a brief excitatory input. During voltage clamp,
      steady monosynaptic input from Ia afferents produced a current that persisted
      after the Ia input ceased. The likely origin of this current was in dendritic
      regions, where plateau potential channels were probably activated due to the lack
      of voltage clamp control during the synaptic input. The functional significance
      of these data is discussed.

PMID- 10084714
TI  - Multiple mechanisms of spike-frequency adaptation in motoneurones.
AB  - Spike-frequency adaptation is the continuous decline in discharge rate in
      response to a constant stimulus. We have described three distinct phases of
      adaptation in rat hypoglossal motoneurones: initial, early and late. The initial
      phase of adaptation is over in one or two intervals, and is primarily due to
      summation of the calcium-activated potassium conductance underlying the medium
      duration afterhyperpolarization (mAHP). The biophysical mechanisms underlying the
      later phases of adaptation are not well understood. Two of the previously
      proposed mechanisms for adaptation are an increase in outward current flowing
      through calcium-activated potassium channels and increasing outward current
      produced by the electrogenic sodium-potassium pump. We found that neither of
      these mechanisms are necessary for the expression of the early and late phases of
      adaptation. The magnitude of the initial phase of adaptation was reduced when the
      calcium in the external solution was replaced with manganese, but the magnitudes
      of the early and late phases were consistently increased under these conditions.
      Partial blockade of the sodium-potassium pump with ouabain had no significant
      effect on any of the three phases of adaptation. Our current working hypothesis
      is that the magnitude of late adaptation depends upon the interplay between slow
      inactivation of sodium currents, that tends to decrease discharge rate, and the
      slow activation or facilitation of a calcium current that tends to increase
      discharge rate. Adaptation is often associated with a progressive decrease in the
      peak amplitude and rate of rise of action potentials, and a computer model that
      incorporated slow inactivation of sodium channels reproduced this phenomenon.
      However, the time course of adaptation does not always parallel changes in spike
      shape, indicating that the progressive activation of another inward current might
      oppose the decline in frequency caused by slow sodium inactivation.

PMID- 10084715
TI  - Analysis of firing behaviour of human motoneurones within 'subprimary range'.
AB  - Firing behaviour of human motoneurones within a low range of frequencies was
      studied during voluntary muscle contraction. It was found that, in contrast to
      the higher 'primary range', both excitability and inhibitibility of these
      motoneurones were significantly higher. As to their minimal firing rates, no
      correlation between them and the reciprocal values of afterhyperpolarization
      (AHP) duration was found. This suggests that AHP can hardly be regarded as the
      main factor controlling the behaviour of human motoneurones within the low
      frequency range of firing and that this range (termed here 'subprimary range')
      should be kept apart from the 'primary range'.

PMID- 10084716
TI  - An influence of afterhyperpolarization on the pattern of motoneuronal rhythmic
      activity.
AB  - Motoneuronal spike trains were generated according to a simple model assuming
      algebraical summation of the afterhyperpolarization (AHP) curve and noisy
      synaptic inflow. An influence of various model parameters on the relationship
      between standard deviation (SD), sigma, of interspike intervals (ISIs) and their
      mean value, Tm, was studied. A typical sigma(Tm) relationship resembled those
      obtained experimentally and consisted of two parts: a short-interval part with
      constant sigma and a long-interval part where sigma increased linearly with
      increasing ISI. It is concluded that the placement of the range of transition
      between short- and long-interval parts of the plot depends on the properties of
      the motoneuron and not on those of the synaptic inflow. The break-point interval
      of the plot is correlated with the AHP duration but is shorter than it. Further,
      not only are the curves for shorter AHP durations shifted towards shorter ISIs,
      but they also have lower SDs at their short-interval parts.

PMID- 10084717
TI  - Properties of human motoneurones and their synaptic noise deduced from motor unit
      recordings with the aid of computer modelling.
AB  - This paper reviews two new facets of the behaviour of human motoneurones; these
      were demonstrated by modelling combined with analysis of long periods of low
      frequency tonic motor unit firing (sub-primary range). 1) A novel transformation
      of the interval histogram has shown that the effective part of the membrane's
      post-spike voltage trajectory is a segment of an exponential (rather than
      linear), with most spikes being triggered by synaptic noise before the mean
      potential reaches threshold. The curvature of the motoneurone's trajectory
      affects virtually all measures of its behaviour and response to stimulation. The
      'trajectory' is measured from threshold, and so includes any changes in threshold
      during the interspike interval. 2) A novel rhythmic stimulus (amplitude-modulated
      pulsed vibration) has been used to show that the motoneurone produces appreciable
      phase-advance during sinusoidal excitation. At low frequencies, the advance
      increases with rising stimulus frequency but then, slightly below the
      motoneurones mean firing rate, it suddenly becomes smaller. The gain has a
      maximum for stimuli at the mean firing rate (the 'carrier'). Such behaviour is
      functionally important since it affects the motoneurone's response to any
      rhythmic input, whether generated peripherally by the receptors (as in tremor) or
      by the CNS (as with cortical oscillations). Low mean firing rates favour tremor,
      since the high gain and reduced phase advance at the 'carrier' reduce the
      stability of the stretch reflex.

PMID- 10084718
TI  - An EMG study of functional cortico-motoneuronal connections in humans.
AB  - We set out to decompose the EMG signal into its constituent motor unit action
      potential components to track motor unit firing rates with a high degree of
      accuracy and extract their average firing rate. We were able to show that this
      average firing rate tracks the subject's force trajectory from beginning to end.
      We propose that this average firing rate is a volitional control signal pointing
      to the existence of a 'volitional unit'. This volitional unit has to do with the
      projection of a group of functionally related cortico-motoneurons on a group of
      spinal motoneurons in the motoneuronal pool of a muscle. Our study of motor unit
      firing patterns during their steady state showed that spinal motoneurons respond
      to a descending central input in a Gaussian manner. We have further shown that
      the central drive itself, as represented by the average firing rate of the active
      motor units, also displays a Gaussian firing behavior. We have also described the
      existence of a 'translation factor', highly correlated to the motor unit size,
      which is unique to each spinal motoneuron and determines the motoneuronal
      response, and its resulting firing rate, to the descending inputs. As for force
      generation, we have shown that expressing the twitch force of a motor unit in a
      dynamic fashion using the 'electrotwitch' concept of firing rate x macro area,
      approximates motor unit force output better and accounts for firing rate related
      force changes more effectively than force estimates based on the mechanical
      twitch.

PMID- 10084719
TI  - End plate spikes in the human electromyogram. Revision of the fusimotor theory.
AB  - 'End plate spike' (EPS) is a spontaneous action potential of a normal striated
      muscle. EPSs are found in local 'active spots' of the muscle. The prevailing
      hypothesis about the origin of EPSs states that when a needle electrode affects a
      motor nerve branch near the neuromuscular junction at the end plate zone, an
      increased leakage of acetylcholine to the synaptic cleft ensues. This elicits
      postsynaptic action potentials of the muscle fibre which can be recorded as EPSs
      with the same needle electrode. Thus EPSs are thought to be caused by needle
      injury or irritation of the motor axon. We suggest that EPSs are action
      potentials of intrafusal muscle fibres and that 'active spots' are in fact muscle
      spindles. Waveform analysis reveals three types of EPSs: small EPSs, not
      propagated outside the active spot either: i) with negative onset; or ii) with
      short positive initial deflection; and iii) large EPSs resembling propagated
      motor unit potentials (MUPs) but with a typical EPS firing pattern, distinctly
      different from that of the MUPs. Study of EPS activation in different manoeuvres
      associates small EPSs with intrafusal gamma motor units and large MUP-like EPSs
      with beta motor units.

PMID- 10084720
TI  - Motoneurons are altered in muscular dystrophy.
AB  - The activity of motoneurons supplying the brachial biceps muscle was examined in
      eight control subjects and 26 patients affected by Duchenne muscular dystrophy.
      The patients were subdivided into two groups: one whose motor units (MU) fired
      with normal rates (N group) and the other whose MU firing rates were higher as
      compared to controls (I group). Firing rates of motoneurons of patients from
      group I increased more rapidly with increasing force level. The relationship
      between the standard deviation of interspike intervals and their mean value,
      sigma(Tm), was shifted towards the shorter intervals and lower standard
      deviations in both groups of patients. The numerical values describing these
      changes correlated with the severity of disease. The MU recruitment was
      comparable for control subjects and for patients. Experimental results as well as
      computer simulations indicate that the break-point of the function sigma(Tm) is
      correlated with motoneuronal properties, and in particular with the
      afterhyperpolarization (AHP) duration. In muscular dystrophy this break-point
      corresponds to the shorter interspike intervals. Therefore, we propose that the
      motoneurons in muscular dystrophy are altered either in response to the muscle
      degeneration or as a result of the disease itself.

PMID- 10084721
TI  - Double discharges of motor units in neuromuscular disorders.
AB  - Repetitive discharges (RDs) are observed in electromyograms recorded from healthy
      as well as diseased muscles. We have evaluated the prevalence of RDs in some
      neuromuscular diseases and analysed the time parameters of recordings displaying
      RDs as well as shapes of the potentials. In our clinical material, RDs have been
      observed exclusively in lower motor neuron lesions, never in healthy or in
      myopathic muscles. The prevalence index of RDs in amyotrophic lateral sclerosis
      (0.06) was found to be different from that in chronic spinal muscle atrophy
      (0.004). The types of double potential shape have been categorised. The
      relationships between the amplitude of the second component and the interspike
      duration and that between the interspike duration and the jitter were calculated.
      The amplitude of the second component diminished and jitter of the components
      increased with the shortening of the interval between components. The authors
      suggest that in lower motor neuron lesions, the RDs of the motorunit (MU) may be
      one of the first signs of the MU's dysfunction.

PMID- 10084722
TI  - Travails of organizing an International Congress.

PMID- 10084723
TI  - The need for the IPTA (International Pediatric Transplant Association)

PMID- 10084724
TI  - Neuropsychological development in children with Hurler syndrome following
      hematopoietic stem cell transplantation.

PMID- 10084725
TI  - Early acute rejection and kidney allograft outcome in children.

PMID- 10084726
TI  - Developments in the clinical science of transplantation during the 20th century.
AB  - Transplantation has become the treatment of choice for end-stage organ failure in
      the four and a half decades since the first successful kidney transplant
      procedure was performed in 1954. The achievements of solid organ transplantation
      can be gauged by the progressive increase in the number of kidney, liver, heart,
      pancreas and lung transplants that are performed annually. Advances in surgical
      technique, immunotherapy, control of opportunistic infections and tissue typing
      have collectively contributed to current 1-year patient survival rates that
      exceed 95% and current 1-year graft survival rates in excess of 85%. This paper
      will review some of the major advances that have lead to the current state of
      transplant immunobiology.

PMID- 10084727
TI  - Recommended immunization practices for pediatric renal transplant recipients.
AB  - To reduce the risk of morbidity and mortality from vaccine preventable disease,
      it is imperative that physicians caring for pediatric renal transplant recipients
      monitor the immunization status of their patients and keep abreast of changes in
      the recommended immunization guidelines. An update of the standard immunization
      guidelines of the AAP, ACIP and AAFP is provided, as well as the necessary
      modifications for and additional vaccines recommended for immunocompromised
      individuals. Where available, data regarding the safety of and response to the
      various vaccines in pediatric transplant patients are provided.

PMID- 10084728
TI  - Tacrolimus in pediatric renal transplantation: a review.
AB  - Tacrolimus is a T cell-specific immunosuppressive agent that has been used in a
      relatively small number of pediatric kidney transplant recipients. It has been
      used as a primary immunosuppressive agent, with patient survival rates of over
      95%, and graft survival rates of over 90%. In the largest series reported, some
      two-thirds of the successfully transplanted recipients have been taken off
      steroids, with substantial catch-up growth, and over 80% have been taken off
      antihypertensive medications. Important complications have included EBV-related
      post-transplant lymphoproliferative disorder and post-transplant diabetes
      mellitus, both reversible. Tacrolimus has also been used to rescue patients with
      refractory acute rejection, with a success rate of 70%-75%. This review
      summarizes the current world experience with tacrolimus in pediatric renal
      transplantation, and describes the details of tacrolimus dosing and the treatment
      of tacrolimus-related complications. On balance, tacrolimus is an effective
      immunosuppressive agent and offers important advantages in the management of
      pediatric renal transplant recipients.

PMID- 10084729
TI  - Adenovirus enterocolitis in human small bowel transplants.
AB  - This report describes two cases of pediatric small bowel transplant patients who
      developed diffuse adenovirus enterocolitis of their allografts. Based upon the
      presenting symptoms for this complication, in both patients a differential
      diagnosis of allograft rejection versus viral infection was clinically
      entertained. The clinical condition in both instances rapidly deteriorated and
      both patients died shortly after the development of the symptoms of fulminant
      septicemia. Autopsies were performed and histologic examination revealed
      extensive denudation of the gastrointestinal mucosa with edema and a marked acute
      and chronic inflammatory infiltrate involving the entire wall of the grafts.
      Numerous viral intranuclear and intracytoplasmic inclusions were evident and an
      immunohistochemical stain specific for adenovirus was strongly positive in the
      infected cells. In addition, while in the first case the adenovirus appeared
      confined to the GI tract, the second patient displayed numerous viral inclusions
      in the lung as well as within multiple liver abscesses. At this point, the
      incidence of adenovirus as a cause of gastroenteritis in small bowel transplant
      patients remains to be determined. We believe that the importance of recognizing
      this particular type of viral infection in this group of patients lies primarily
      in differentiating it from other viral organisms (e.g., CMV) that require a
      specific antiviral therapy. Moreover, an identification of this entity could help
      avoid a misdiagnosis of rejection which could lead to an unnecessary increase in
      immunosuppressive therapy and a possible exacerbation of the underlying
      condition.

PMID- 10084730
TI  - Pleural disease in patients undergoing lung transplantation for cystic fibrosis.
AB  - Cystic fibrosis (CF) is associated with varying degrees of pleural inflammatory
      reaction that occurs as a result of chronic pulmonary infections and intervention
      to pleural space. The amount of pleural reaction is associated with the
      difficulty involved when performing the pneumonectomy at the time of lung
      replacement. The aim of this study is to identify possible pre-transplantation
      parameters that may predict the extent of pleural adhesion density. The charts of
      the 32 CF patients who underwent lung transplantation were reviewed. The degree
      of pleural adhesions was graded as none, minimal, moderate or severe, by
      extensive retrospective chart review of the operative and pathology reports.
      Available Brasfield radiographic scores, chest computerized tomographic (CT) scan
      scores, and pulmonary function test results were correlated to the pleural
      density grades. CT scans were scored by one radiologist as none, mild focal,
      moderate focal, diffuse mild or severe pleural disease. The presence of severe
      adhesions was associated with lower diffusion capacity corrected for volume
      (DL(CO)/VA) (p=0.0022) and older age (p<0.05) at the time of transplant. The
      typical radiographic and pulmonary function findings of airway obstruction,
      parenchymal nodularity and air trapping did not correlate with pleural adhesion
      density. The eleven patients with severe pleural adhesions had a longer ICU
      course and remained intubated longer than the thirteen patients with none or
      minimal adhesions. The extent of severe adhesions associated with CF cannot be
      predicted by preoperative Brasfield radiographic scores of parenchymal disease or
      spirometry data. However, chest CT imaging and DL(CO)/VA measurements may be
      useful in predicting the extent of pleural adhesions and the degree of dissection
      difficulty associated with the pneumonectomies for lung transplantation in the CF
      recipients.

PMID- 10084731
TI  - Primary BK virus (BKV) infection due to possible BKV transmission during bone
      marrow transplantation is not the major cause of hemorrhagic cystitis in
      transplanted children.
AB  - In allogeneic bone marrow transplanted (BMT) patients BK virus (BKV) reactivation
      has been associated with haemorrhagic cystitis (HC). However, it is far from
      obvious which patients will develop HC, since BKV, a human polyomavirus, is
      ubiquitious and infects children at an early age. To investigate if a primary BKV
      infection, as such or possibly due to transmission of BKV by the marrow graft
      during BMT, was correlated to the development of HC, 45 children were followed
      for possible BKV seroconversion and development of HC at different time points
      after BMT. Serum samples were collected from the 45 allogeneic BMT children and
      their donors before transplantation, and from the patients at 3, 6 and 12 months
      after BMT. These sera were analysed for the presence of specific antibodies
      towards BKV by hemagglutination inhibition (HAI) and by IgG- and IgM-class
      specific enzyme linked immunosorbent (ELISA) assays. Twelve of the 45 BMT
      children had a documented episode of HC or hematuria. All patients and 98% of the
      donors were HAI positive before BMT, while with ELISA 87% of the patients and 84%
      of the donors were positive. Moreover, most HC and hematuria children (11/12)
      were seropositive with both assays before BMT, making it impossible to
      investigate possible BKV transmission through the bone marrow graft during BMT by
      serology. Still, serological changes such as ELISA seroconversion, IgM antibodies
      and/or HAI titer increases were significantly (p=0.016) more common in patients
      with HC (58%) than without HC (24%), but these changes occured mainly after HC
      symptomatology had already resolved. However, there was a near significant
      difference (p=0.053) in BKV seroprevalence by ELISA among the donors of patients
      with HC or hematuria (67%) as compared to the donors (91%) of patients without
      HC.

PMID- 10084732
TI  - Renal graft survival in children with early acute rejection.
AB  - Acute rejection episodes (AREs) are an important cause of morbidity and mortality
      in children following renal transplantation. For the purpose of this study, the
      diagnosis of early rejection was established when it developed within the first 6
      months post-transplantation. The impact of an early ARE on patient and graft
      survival areas was studied in 44 patients who received their grafts between
      January 1987 and December 1995. Group I (GI) was comprised of 25 patients who
      developed 30 ARE. They were compared to 19 age- and sex-matched controls without
      ARE, group II (GII), who were transplanted during the same time-period and
      received similar long-term immunosuppressive triple therapy, oral prednisone,
      azathioprine and cyclosporine A. The ARE was confirmed by renal biopsy in 83% of
      the cases. Morbidity, mortality and graft function were assessed statistically at
      baseline, 12 and 24 months after transplantation. Seven GI patients lost their
      grafts during an ARE; in 4 cases death that was related to opportunistic
      infections presenting during or soon after anti-rejection therapy, whereas 3
      patients who survived lost their grafts due to thromboses or infections, also as
      a consequence of ARE. The GI graft survival rates were 76% and 72% at 12 and 24
      months post-transplant, respectively, whereas the graft survival rate of GII
      patients was 100% at both evaluation periods. The patient survival rate was 84%
      in GI and 100% in GII patients at 24 months. No statistically significant
      differences of renal function were found between and/or within groups at 12 and
      24 months. Recipients of living related donor (LRD) and cadaveric donor (CD)
      kidneys were evaluated independently of the group to which they were allocated.
      The acute rejection ratio (number of AREs/number of transplants) was 0.61 in LRD
      and 0.38 in CD (differences non-significant). This study concludes that AREs are
      an important cause of patient and graft loss, with opportunistic infections being
      a major threat to be considered during aggressive anti-rejection therapy. The
      renal function was normal after long-term follow-up in both groups of patients,
      regardless of ARE.

PMID- 10084733
TI  - The use of partially HLA-mismatched donors for allogeneic transplantation in
      patients with mucopolysaccharidosis-I.
AB  - Allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling appears
      to improve survival and diminish some of the physiologic derangements seen in
      children with mucopolysaccharidosis (MPS)-I (Hurler Syndrome), an inherited
      metabolic storage disease resulting from the lack of alpha-L-iduronidase enzyme
      activity. Death is usually expected in the first decade of life. Unfortunately,
      most patients lack an HLA-matched sibling donor and alternative donors have been
      identified for transplant. This study reports on a five-year median follow-up
      (range: 985-2,355 days) in 11 Hurler Syndrome patients who underwent allogeneic
      BMT from partially mismatched related donors (PMRDs). The median age was 20
      months (range: 11-44 months). The overall survival rate was 64% (95% CI 34-94%).
      The overall graft failure rate (36%) was higher than reported with matched
      sibling BMT. All patients with sustained engraftment experienced improvement in
      physical manifestations, such as corneal opacity, gum and tongue hypertrophy,
      hepatosplenomegaly and joint mobility. Skeletal abnormalities, such as dysostosis
      multiplex, were stabilized but not reversed. Some patients have continued to show
      decline in neuropsychometric testing, while others appear to stabilize and one
      has demonstrated improvement. Until better methods for replacing enzyme activity
      are developed, BMT from a matched sibling of alternative donors can be considered
      a viable intervention for Hurler Syndrome patients to achieve partial improvement
      or stabilization from the deterioration caused by substrate storage, particularly
      in minimally affected patients early in life.

PMID- 10084734
TI  - Renal transplantation in children with congenital nephrotic syndrome: a report of
      the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - The database of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) was examined to identify factors that contribute to the poor transplant
      outcome rate seen in patients with Congenital Nephrotic Syndrome (CNS) (1).
      Between January 1, 1987 and January, 1997, 132 transplant recipients with the
      primary diagnosis of CNS were registered. Analysis of the index renal transplants
      for 78 living donor transplants (LDTx) and 54 cadaver transplants (CADTx)
      revealed a graft failure rate of 20.5% and 50.0%, respectively. A proportional
      hazards regression analysis of the CNS patients indicated that cadaver donor
      source (relative risk increase of 3.9, p<0.001) and recipient age less than 2
      years of age (relative risk increase of 2.6, p=0.002) were simultaneous
      significant predictors of poor graft survival. Patients with CNS demonstrated
      decreased graft survival compared to the remainder of the registry adjusted for
      age and donor source (p=0.04). Graft failures were attributed to vascular
      thrombosis (26%), patient death with functioning graft (23%), chronic rejection
      (21%) and acute rejection (19%). Graft failure attributed to thrombosis occurred
      more frequently in CNS patients than in patients with other primary diseases
      (8.3% vs. 2.9%, p=0.002). Graft failure due to patient death with a functioning
      graft also occurred more frequently in CNS patients than in patients with other
      primary diseases (7.5% vs. 2.6%, p<0.003). Infections were the causes of death in
      50% (5 of 10) of CNS patients with a functioning graft. Infection as a cause of
      death with functioning grafts was significantly greater in CNS patients (3.8%)
      than the rest of the registry (0.8%, p<0.006). We conclude that there is a high
      rate of renal graft failure in pediatric patients with CNS. Vascular thrombosis
      and death with a functioning graft were more frequent in patients with CNS
      compared to patients with other primary diseases. Care should be taken to
      eliminate risk factors for hypercoagulability and infections prior to
      transplantation in children with CNS.

PMID- 10084735
TI  - Effect of parental donor sex on rejection in pediatric renal transplantation: a
      report of the North American Pediatric Renal Transplant Cooperative Study.
AB  - Using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)
      database, we performed a retrospective cohort study of 1,552 pediatric renal
      transplant patients who had received a graft from a biological parent to
      determine if parental donor sex influences the development of rejection. There
      were 102/675 (15.1%) graft failures in paternal grafts compared to 144/877
      (16.4%) graft failures in maternal grafts. Overall graft survival (p=0.48) and
      time to first rejection (p>0.9) were not different in patients receiving paternal
      versus maternal grafts. The overall frequency of graft loss to rejection was also
      not different. However, maternal donation was associated with a significantly
      longer time to first rejection in patients less than one year of age at the time
      of transplantation (p=0.01). Time to first rejection was not different between
      maternal and paternal grafts in older recipients. In summary, the present study
      did not demonstrate a difference in graft survival between maternal and paternal
      donations, but the youngest patients may experience a longer time to first
      rejection with maternal donation. The number of young patients is small, however,
      and further data are necessary to confirm this observation.

PMID- 10084736
TI  - Probable false positive coccidioidal serologic results in patients with cystic
      fibrosis.
AB  - Coccidioidomycosis is an acquired fungal infection that afflicts primarily the
      respiratory tract. Cystic fibrosis patients who are being treated with
      glucocorticoids and immunosuppressed organ recipients may be at risk for
      infection with Coccidiodes immitis or reactivation of latent infection. The
      diagnosis is best made by demonstration of the organism in pathologic specimens
      or by culture. Serologic screening is another method that is reliable in most
      patients. We studied 98 patients who had serologic screening for Coccidiodes
      immitis performed as part of their evaluation for lung transplantation. This
      study revealed that approximately 15% of the cystic fibrosis patients screened
      had putative coccidioidal IgM, in the absence of an IgG response. None of the
      patients studied had a positive fungal culture for the organism. None of the non
      cystic fibrosis patients screened had detectable coccidioidal IgG or IgM. We
      hypothesize that cystic fibrosis patients may have hyperimmune sera which
      interferes with serologic screening tests. We would recommend repeat serologic
      testing and attempts to identify the organism in tissue or by culture to confirm
      the diagnosis in these patients.

PMID- 10084737
TI  - The impact of donor source, recipient age, pre-operative immunotherapy and
      induction therapy on early and late acute rejections in children: a report of the
      North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Acute rejection is a frequent event in pediatric transplantation. In addition to
      graft loss, acute rejection episodes stimulate the development of chronic
      rejection and inhibit growth in children post-transplantation. In this study, we
      analyzed our data from 1987 through 1996 to identify acute rejection episodes in
      children. In 2,520 living donor (LD) transplants there were 2,540 rejection
      episodes (rejection ratio: 1.1), and in 2,579 cadaver donor (CD) transplants
      3,653 episodes were observed (rejection ratio: 1.32). For LD recipients the first
      rejection occurred sooner when there was at least one HLA-DR mismatch (RR=1.6,
      p<0.001) and prophylactic T-cell antibody was not used (RR=1.4, p<0.001). For CD
      transplants absence of prophylactic T-cell antibody (RR=1.2, p<0.001) and donor
      age below five years were risk factors (RR=1.5, p<0.001). Late initial acute
      rejections were seen in 327 of 1,471 patients (22.2%) who were rejection free at
      one year. At risk for the development of late rejections were children over the
      age of six years at transplantation (RR=1.7, p<0.001) and children of non-white
      origin (RR=1.5, p <0.002). For LD transplant recipients in the age range of 0-5
      years, irreversible rejection was observed in 8.7% compared to 4.1% for older
      children (RR=1.46, p<0.001). Similar results for CD transplants were 12.6% versus
      6.6% (RR=1.5, p<0.00). The high frequency of rejection episodes in children and
      the greater irreversibility in younger children suggest pediatric patients may
      have a more robust immune response. Current ongoing studies in the molecular
      mechanisms of the pathogenesis of rejection in surveillance biopsies of children
      may help determine if this hypothesis is valid.

PMID- 10084738
TI  - Chimerism after allogeneic hematopoietic cell transplantation: time for a
      paradigm shift?

PMID- 10084739
TI  - Renal transplantation in children with Down syndrome.

PMID- 10084740
TI  - Living donor lobar lung transplantation: the pediatric experience.
AB  - Living donor (LD) lobar lung transplantation is now an accepted alternative to
      cadaveric lung transplantation in selected patients with end-stage lung disease.
      This study reviews the Childrens Hospital Los Angeles LD experience of 17
      patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end
      stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had
      bronchiolitis obliterans. LD candidates must meet the same criteria as for
      cadaveric lung transplant candidates. Donor candidates are rigorously screened
      (physically and psychologically) prior to acceptance for lobectomy. LD patients
      receive the same triple immunosuppression regimen as our cadaveric recipients
      (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of
      rejection episodes, incidence of bronchiolitis obliterans, pulmonary function
      tests, exercise stress tests, and cardiac catheterization data was made between
      LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes
      were also reviewed. In our pediatric program, the 1-year survival rate for LD
      recipients is currently 81%, which compares favorably with the ISHLT average of
      70% for pediatric transplant patients. The incidence of rejection is about the
      same for LD and CL recipients, but the episodes are less severe for pediatric LD
      patients. There have been no histological cases of bronchiolitis obliterans
      syndrome in our LD recipients. Although there have been questions as to whether
      transplanted lobes can supply comparable pulmonary reserve to whole cadaveric
      lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise
      stress tests, and pulmonary artery pressures (no evidence of pulmonary
      hypertension) in LD patients are not significantly different to CL recipients in
      our institution. Besides pain from the thoracotomy, the donors have a decrease of
      16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital
      capacity. Otherwise, there have been no major complications to the donors and
      most have resumed their usual activities. Based on outcomes, pulmonary function
      tests, exercise stress tests, and hemodynamic studies as well as low donor
      morbidity, living donor double lobar lung transplantation is a viable alternative
      to cadaveric lung transplantation in selected pediatric patients with end-stage
      lung disease.

PMID- 10084741
TI  - Peripheral blood stem cell transplantation in young children: experience with
      harvesting, mobilization and engraftment.
AB  - The purpose of this study was to determine the feasibility and assess optimal
      timing of harvesting peripheral blood stem cells (PBSC) for transplantation in
      young children. Thirteen children with body weight less than 25 kg, mean age of
      3.9 years (1-9 yrs) who had recurrent solid tumors and leukemia were given tumor
      specific chemotherapy followed by i.v. rhG-CSF (5 microg/kg/d) for stem cell
      mobilization. Cytaphereses were done through a central venous line (CVL) during
      the marrow recovery phase (WBC >0.5 x 10(9)/l). The phereses were analyzed
      separately and assigned to three groups depending on the WBC at the time of the
      pheresis: Group I (WBC <1.0 x 10(9)/l), Group II [WBC in the range 1.0-3.0 x
      10(9)/l] and Group III (WBC >3.0 x 10(9)/l). Samples from each harvest were
      assayed for cell count, CFU-GM, BFU-E, CD34+ cell count, and tumor cell
      immunocytology in patients with neuroblastoma (NBL). A median of 3.2 x 10(8)
      mononuclear cells per kg (MNC/kg), [mean 2.8 x 10(8) MNC/kg, standard error of
      the mean (SEM) +/- 0.74 (1.1-4.7)] were infused following myeloablative therapy.
      78 phereses were performed in 13 children with a median weight of 18 kg (10-25
      kg). A median of 5 phereses were performed per patient. There were no significant
      differences in the percentage and number of CD34+ cells, CFU-GM or BFU-E colonies
      assayed by plating 0.5 x 10(5) cells. Differences could be found in the total
      number of MNC (p<0.008) and the number of MNC/kg (p<0.001) between Groups II and
      III. No tumor cell contamination was detected in the NBL patients by
      immunocytology. All patients were rescued with PBSC and achieved sustained white
      cell engraftment (ANC >0.5 x 10(9)/l) at a median of 13.5 d (10-25 d) and
      platelet engraftment (untransfused platelet count >20.0 x 10(9)/l) at a median of
      29 d (12-63 d). The only toxicity encountered during the phereses was
      thrombocytopenia in 4 patients whose median post-pheresis platelet count was 6.0
      x 10(9)/l (3.0-9.01). It is concluded that collection of PBSC in young children
      is feasible and safe and can be performed through a cuffed CVL at the time of WBC
      recovery post mobilization with chemotherapy and G-CSF. Cytopheresis can be
      effectively performed when the peripheral WBC count approaches 1.0 x 10(9)/l.
      Following stem cell infusion, engraftment was prompt and durable.

PMID- 10084742
TI  - Benign transient hyperphosphatasemia of infancy and early childhood following
      cardiac transplantation.
AB  - The phenomenon of a transient very high rise in serum alkaline phosphatase,
      associated with either trivial illness or no symptoms, in early childhood has
      been described previously in otherwise normal children. We describe here what we
      believe are the first published reports in two children who have previously
      undergone orthotopic cardiac transplantation. They were found to have a very high
      serum alkaline phosphatase, with features consistent with a diagnosis of
      transient hyperphosphatasemia of infancy and early childhood. The importance of
      early recognition and avoidance of overinvestigation are discussed.

PMID- 10084743
TI  - Clinical relevance of in vitro propagation of activated lymphocytes from
      endomyocardial biopsy samples of pediatric heart transplant recipients.
AB  - In vivo activated T-lymphocytes can be cultured from endomyocardial biopsy
      samples of human cardiac allografts, sometimes even in the absence of
      histological rejection. We investigated the clinical relevance of this
      "lymphocyte growth assay" in pediatric heart transplant recipients. Specifically,
      we wished to determine if: (i) positive lymphocyte growth from EMB samples in the
      absence of significant rejection identifies a patient as being at increased risk
      for the development of acute rejection; (ii) withdrawal or major dose reduction
      of corticosteroids in the presence of lymphocyte growth results in high risk of
      rebound rejection; and (iii) presence of lymphocyte growth during acute rejection
      helps predict the response to treatment. Cultures were performed on 789
      consecutive EMB samples from 65 pediatric heart transplant recipients in media
      containing 30 U/ml of recombinant IL-2. T-lymphocytes were cultured from 16% of
      EMB samples with low grade rejection (grade 0-1b) and from 34% of EMB samples
      with grade 2-4 rejection. EMB samples obtained early post-transplant (<180 days)
      were significantly more likely to yield positive lymphocyte growth compared to
      biopsies obtained late for any given rejection grade. Lymphocyte growth was
      comparable between patients managed with cyclosporine or tacrolimus based
      immunosuppression. For 227 EMB samples without rejection, a subsequent EMB sample
      was obtained within 12 weeks. Lymphocyte cultures were positive in 47 of these
      227 EMB samples (21%), and in 19 out of 47 (40%) cases acute rejection (grade 2
      4) was present on the follow-up EMB sample. By contrast, of 180 biopsies without
      growth, only 29 (16%) showed rejection at the next EMB (p<0.0001). When a follow
      up biopsy was performed within 12 weeks of corticosteroid withdrawal, "rebound
      rejection" was observed in 3 out of 10 (30%) cases where the previous EMB sample
      yielded positive lymphocyte growth and in 4 out of 38 (11%) cases when it did not
      (p=0.29). The presence of lymphocyte growth in association with rejection was
      also predictive of whether rejection would resolve following high dose
      intravenous corticosteroid therapy (persistent rejection in 33 out of 50 (66%)
      cases with positive growth, versus 25 out of 80 (31%) cases without growth
      (p<0.0001)). Thus, positive lymphocyte growth is strongly associated with higher
      grade of rejection and earlier time from transplantation. Lymphocyte growth in
      the absence of rejection indicates high risk for rejection within the next 12
      weeks. Growth in association with acute rejection indicates high probability of
      persistence of rejection following treatment with high dose corticosteroids.

PMID- 10084744
TI  - Transplanted small bowel and expression of the insulin-like growth factor binding
      proteins.
AB  - The insulin-like growth factor binding proteins (IGFBPs) act to modulate the
      growth and differentiation of the gastrointestinal mucosa by regulating cellular
      responses to the important mitogens, the insulin-like growth factors (IGFs). The
      transplanted small bowel must maintain the normal growth factor
      interrelationships and signaling pathways despite the potential of host
      rejection. Ostomy effluent of patients after small bowel or combined liver/small
      bowel transplantation was assayed for IGFBPs to investigate the effect of
      rejection on the IGF-IGFBP axis. Seventeen patients were studied over an 18-month
      period. The transplanted small bowel produced no measurable IGFBPs in the ostomy
      effluent under normal circumstances. However, when rejection was taking place the
      ostomy effluent was found to have measurable IGFBP levels in 6 of 12 episodes,
      the 6 episodes occurring in 6 different patients. Mostly, the IGFBPs present did
      not exhibit a serum-like pattern indicating the secretion of IGFBPs into the
      effluent was not the result of loss of mucosal barrier integrity. There were no
      statistically significant differences in protein content of the ostomy fluids in
      the presence or absence of rejection. Our results suggest that the
      gastrointestinal IGF axis is altered during some instances of transplanted small
      bowel rejection, with increased secretion of IGFBPs.

PMID- 10084745
TI  - Renal transplantation in Down syndrome: a report of the North American Pediatric
      Renal Transplant Cooperative Study.
AB  - There are few published reports on renal transplantation in patients with Down
      syndrome and renal failure. By means of a questionnaire sent to participating
      renal centers of the North American Pediatric Renal Transplant Cooperative Study,
      this study identified 14 Down syndrome patients who received renal transplants
      between January 1987 and November 1995. There were 6 males and 8 females between
      the ages of 6 and 21 years. Of the group, 8 patients were Caucasian and 6 were of
      African American ethnicity. Four patients had a primary diagnosis of obstructive
      uropathy, two had hypoplastic/dysplastic renal disease, two had focal segmental
      glomerulosclerosis, two had a diagnosis of chronic glomerulonephritis and four
      patients had unspecified diagnoses. Eight patients received cadaver kidneys
      whilst the other six had a living related transplant from a parent or sibling.
      Only one patient had received a prior kidney transplant, ten patients were on
      dialysis at the time they were transplanted and 4 patients were preemptively
      transplanted. Standard immunosuppression with Cyclosporine, Imuran and Prednisone
      was used. In addition, nine patients received induction therapy at the time of
      transplantation. Follow-up data revealed that 5 grafts (35.7%) had failed, two as
      a result of rejection and three due to patient death. At the time of data cutoff
      there were 3 deaths, one due to viral infection and the other two secondary to
      cardio-pulmonary complications.

PMID- 10084746
TI  - Sequential analysis of the lipid profile of children post-renal transplantation.
AB  - Persistent hyperlipidemia and hypercholesterolemia post-transplantation are risk
      factors for accelerated atherosclerosis. To evaluate the natural history of lipid
      abnormalities in children post-transplantation, this study utilized a cohort of
      29 patients who were all treated with the same three- drug maintenance
      immunosuppression (cyclosporine, azathioprine, and prednisone) and whose dosing
      regimen was rigidly controlled. Fasting blood samples were taken monthly to
      determine lipid profiles measuring total cholesterol (CHOL), triglycerides (TG),
      high-density lipoprotein cholesterol (HDL), very low density lipoprotein
      cholesterol (VLDL), and levels of lipoprotein (a) (LP(a)). A mean value was
      determined for each of five time periods: 0-3 months, 3-6 months, 6-9 months, 9
      12 months and 12-15 months post-transplant. A single specimen of fasting lipid
      profile was drawn from 21 non-immunosuppressed children attending an ambulatory
      pediatric clinic and used as control. Despite significant reductions in the
      cyclosporine and prednisone doses post-transplantation, significant reduction in
      any of the lipid parameters was only noted after the first year. Reductions in
      the HDL fraction and in the TG level were noted during the 12-15 month period,
      however the values obtained in the patient population were significantly elevated
      for CHOL, TG, LDL and VLDL compared to controls. This study, using a fixed
      protocol, suggests that the lipid profile should be measured at one year post
      transplant in all transplant patients, and if subsequent follow-up continues to
      exhibit abnormally elevated levels of CHOL and LDL, interventional therapy should
      be considered.

PMID- 10084747
TI  - Recovery of ceftazidime-resistant Klebsiella pneumoniae from pediatric liver and
      intestinal transplant recipients.
AB  - The purpose of this report was to determine the frequency of colonization and
      bacteremia with ceftazidime-resistant Klebsiella pneumoniae among pediatric
      candidates for and recipients of liver (LTx) and/or intestinal (ITx)
      transplantation. Between January and December 1994, surveillance stool cultures
      obtained from 51 children on the abdominal transplant service were planted on a
      selective medium containing 2 microg/ml of ceftazidime. Isolates of K. pneumoniae
      which grew on the selective medium were screened for extended-spectrum beta
      lactamase (ESBL) production by the double-disk synergy test and underwent
      microdilutional susceptibility testing. Strain relatedness of ceftazidime
      resistant K. pneumoniae was analyzed by field inversion gel electrophoresis
      (FIGE). Sixteen of 51 patients had > or = 1 positive stool cultures for
      ceftazidime-resistant K. pneumoniae; 9 out of 16 on the first culture obtained 1
      23 days (median = 5) after admission. All 9 had been in hospital prior to this
      admission. Four others were positive on their first culture but were in our
      hospital for > 1 month at the onset of the study. Three patients became colonized
      after admission. Colonization with ceftazidime-resistant K. pneumoniae was more
      frequent among recipients of ITx (including combined LTx-ITx) compared to LTx
      alone (7/13 vs. 7/32, p<0.05). All of the ceftazidime-resistant isolates
      recovered from surveillance stool cultures had positive double-disk diffusion
      tests suggesting the presence of ESBL production as the mechanism of resistance.
      Ceftazidime resistance was identified in 7/8 episodes of bacteremia due to K.
      pneumoniae in patients on the abdominal transplant service compared with 0/17
      episodes in other children in the Children's Hospital of Pittsburgh during the
      study. During this same time period, 69/312 clinical isolates of K. pneumoniae
      evaluated in the hospital laboratory were ceftazidime-resistant; 67/69 came from
      patients on this service. In none of the 312 isolates was resistance to
      cefotaxime found in the absence of ceftazidime resistance. Unique clones were
      identified for 10/19 isolates of ceftazidime-resistant strains of K. pneumoniae
      analyzed by FIGE. Colonization and bacteremia with ceftazidime-resistant K.
      pneumoniae were commonly identified among recipients of LTx & ITx at the
      Children's Hospital of Pittsburgh. The mechanism of resistance appeared to be due
      to the presence of ESBL production by resistant strains. Although resistant
      strains were frequently recovered from patients on the abdominal transplant
      service, recovery of ceftazidime-resistant strains from patients outside of this
      service was rare even in the intensive care setting.

PMID- 10084748
TI  - Glomerular filtration rate in children following renal transplantation.
AB  - Most studies evaluating renal function post-renal transplantation in children
      have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When
      renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular
      filtration rate (GFR), especially during cyclosporine therapy. This study
      measured GFR in 64 children (age range: 4-19 years) with stable renal function
      who received renal allografts at the Childrens Medical Center of Dallas, 31 from
      live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate
      clearance (C(IO)) was used as the reference standard for measuring GFR. Data from
      100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO)
      performed during the first year after renal transplantation in 23 children who
      received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/
      7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05).
      Beyond the first year post-renal transplantation there was no difference in C(IO)
      between LRD and CAD allografts. When S(Cr) was compared to C(IO), the
      relationship was nonlinear. C(IO) was also compared to the simultaneous
      estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH)
      was inversely proportional to the level of renal function. When renal function
      was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely
      approximated C(IO). When renal function was moderately to severely curtailed
      (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%.
      The study concludes that in children with renal transplant: 1) C(IO) is higher in
      allografts from LRD compared to CAD kidneys only in the first 12 months following
      renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH)
      consistently overestimates GFR children following renal transplantation unless
      renal function is normal or only mildly decreased.

PMID- 10084749
TI  - Allogeneic bone marrow transplantation in Fanconi anemia from Turkey: a report of
      four cases.
AB  - Bone marrow transplantation (BMT) is currently the treatment of choice for
      patients with Fanconi anemia (FA) if a suitable donor is available. Four children
      with FA underwent allogeneic BMT from HLA-identical siblings during the period
      from 1995 to 1996. Pretransplant conditioning was Cyclophosphamide (Cy) (20
      mg/kg) + Thoracoabdominal irradiation (TAI) (500 cGy) +/- Antithymocyte globulin
      (ATG) (2 mg/kg/day x 3). Cyclosporin A (CsA) was used as GvHD prophylaxis. The
      time of neutrophil (ANC>500) and platelet (>50,000) recovery were at 11-14 and 17
      25 days, respectively. One patient with a pretransplant history of multiple
      transfusions experienced graft rejection and died at day +29 with infection and
      bleeding. Although three patients sustained engraftment one developed donor
      originated acute lymphoblastic leukemia (ALL) 18 months after BMT and died with
      CNS hemorrhage and infection at +25 months following 7 months of chemotherapy.
      None of the patients developed grade 3-4 acute GvHD. Cytotoxicity included grade
      II mucositis in all and severe gastroenteritis in one patient. During a follow-up
      period of 10 months and 2 years, two patients are well with normal blood count,
      recovering immune function and have a Karnofsky score of 90%.

PMID- 10084750
TI  - Pediatric renal transplantation in the Nordic countries: a report of the Nordic
      Pediatric Renal Transplant Study Group.
AB  - The Nordic Pediatric Renal Transplant Study Group was organized in 1994 to
      register and follow children under 16 years of age who receive renal allografts
      in the Nordic countries. It comprises all transplant centers in Scandinavia, four
      in Sweden, three in Denmark and one each in Norway and Finland. The following
      report is based on 430 transplantations performed in 1982-1996. 343 were first
      transplants and 57 were retransplants. The mean annual incidence of renal
      transplantations per million children below 16 years of age was 7.4. The mean
      incidence of retransplantations was 1.0 and therefore the mean incidence of
      primary transplantations was 6.5 per million children below 16 years of age. 12%
      of the children were less than 2 years of age, 20% 2-5 years of age and 68% 6-15
      years of age. 231 (54%) of the transplants were performed with grafts from living
      related donors (LD) and 199 (46%) with cadaveric grafts (CD). 72% of the children
      had congenital renal disorders and 28% acquired diseases. Cyclosporine-based
      immunosuppressive protocols were used in all centers. Antibody induction therapy
      (polyclonal or monoclonal) was used by only three of the nine participating
      centers. The mean 1-year graft survival rate for all age groups was 88% for
      recipients of living-donor grafts and 78% for recipients of cadaveric donor
      grafts.

PMID- 10084751
TI  - Varicella after kidney transplantation.

PMID- 10084752
TI  - Future of living-related small bowel transplantation in children.

PMID- 10084753
TI  - Corticosteroid elimination in pediatric solid organ transplantation.

PMID- 10084754
TI  - Central role for CD40/CD40 ligand (CD154) interactions in transplant rejection.
AB  - Major advances have been made in understanding the expression and function of
      CD40 and its ligand CD154. It is now clear that CD40/CD154 interactions are
      critical in many aspects of the immune response, including T cell activation, T
      cell-dependent macrophage activation, T cell-B cell interactions and endothelial
      activation. Moreover, increasing evidence supports a central role for CD40/CD154
      interactions in the immune processes of allograft rejection. Functional studies
      using blocking monoclonal antibodies have revealed beneficial effects of
      interupting CD40/CD154 co-stimulation in animal models of transplantation,
      particularly in association with interuption of the CD28/B7 pathway. A next step
      is to develop new therapeutic approaches to interrupting this pathway in humans,
      either through the development of receptor antagonists or through the
      understanding of intracellular signaling pathways utilized by these molecules.

PMID- 10084755
TI  - Current status of living-related liver transplantation.
AB  - Living-related liver transplantation has come of age. This manuscript addresses
      the most important facets of the living-related liver transplant procedure
      including selection of the donor, the recipient operation, immunosuppression and
      rejection as well as the most common surgical complications. It also describes
      the results in terms of patient and graft survival, retransplantation and quality
      of life. Although living-related liver transplantation has not solved the problem
      of organ shortage, it has provided many children with an opportunity to live and
      enjoy life.

PMID- 10084756
TI  - ABO-mismatched renal transplantation in children: a report of the North American
      Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the Midwest Organ Bank
      (MOB).
AB  - Successful ABO-mismatched renal transplantation (RT) (blood group A2 donor to
      blood group B or O recipient) has occurred in adults in the setting of a low
      titer (< or =4) natural isoagglutinin (anti-A) level in the recipient of the
      mismatched organ. Similar experiences have rarely occurred in children. Between
      1986-1996, 11 pediatric patients (6 male and 5 female) received 11 ABO-mismatched
      kidneys [7 cadaveric (CAD) and 4 living related donor (LRD)]. There were 8 O
      recipients/A2 donor pairs, 2 B recipients/A2 donor pairs and 1 B recipient/A2B
      donor pair. Recipient age at the time of RT was 14.7+/-3.0 yr (mean +/- SD).
      Prior to RT, 2 recipients underwent splenectomy and none received donor-specific
      transfusions. Induction and early maintenance immunosuppression consisted of
      corticosteroids (11 pts), ALG/ATG (6 pts), OKT3 (3 pts), azathioprine (11 pts)
      and cyclosporine (8 pts). The mean 30-d cyclosporine dosage was 10.6+/-4.0
      mg/kg/d. Eight patients suffered > or =1 acute rejection episodes, the initial
      episode occurring within the first 31 d post-transplant in 7 of them. Five grafts
      (45.4%) failed secondary to vascular thrombosis (1), acute rejection (2) and
      chronic rejection (2). The remaining grafts (54.5%) all functioned for >1000 d
      (range: 1023-3746 d). The pre-transplant anti-A titer was determined in 6 pts; in
      4 it was low (2) and in 2 it was high (8). Graft survival in all but one of these
      patients (whose titer was 8 and who suffered a non-rejection-related vascular
      thrombosis) was > or =2 yr. In summary, ABO-mismatched RT in pediatric patients
      is an uncommon practice. However, the adult experience and our preliminary
      pediatric experience suggests that evaluation of recipient isoagglutinin levels
      in this setting may be helpful in the selection of donor/recipient pairs in whom
      mismatched transplantation can be successful.

PMID- 10084757
TI  - Somatic growth in infant heart transplant recipients.
AB  - Infant heart transplantation is now entering its second decade of clinical
      experience. To understand better issues relating to somatic growth, this
      retrospective study will describe growth patterns in a group of infant heart
      transplant recipients. Early growth: growth velocity from birth to
      transplantation in 77 infants transplanted before 6 months of age was compared
      with growth velocity from transplant to 3 months. Growth from 3 to 6 months and
      from 6 to 12 months after transplantation is described. Growth velocities (mean
      +/- SD) for weight (g/d) and length (cm/yr) for these 4 time periods respectively
      were: 7+/-14 and 27+/-22, 32+/-9 and 35+/-14, 17+/-7 and 24+/-10, 12+/-6 and 17+/
      8. Growth velocities for both weight (p<0.01) and length (p = 0.04) were
      significantly improved in the first 3 months after transplantation. Late growth:
      Growth beyond 5 yr post-transplantation was described in a group of 51 infants
      transplanted in the first year of life and who survived at least 5 yr (median 6.8
      yr, range 5.0 to 10.9). Most recent growth parameters (z-score; mean +/- SD)
      were: weight -0.55+/-1.2, height -0.48+/-0.97 and weight for height -0.16+/-0.96.
      Factors (with significant p-values) evaluated for their possible influence on
      late height (<5th percentile vs. > or =5th percentile) were: age at transplant,
      hospital days from transplant to discharge, hospital days 1st year after
      transplantation (p = 0.019), hospital days after 1st year, rejection episodes 1st
      year, rejection episodes 1-5 yr (p = 0.02) mid-parental height (p = 0.008) and
      isotopic glomerular filtration rate (p = 0.055). CONCLUSION: Growth while
      awaiting infant heart transplantation is poor, but adequate catch-up growth does
      occur. Beyond 5 yr most (88%) infant heart transplant recipients have weight and
      height in the normal range. Early illness, late rejection and genetic growth
      potential may play the largest role in later height attainment.

PMID- 10084758
TI  - Cyclosporin A (Neoral) in pediatric organ transplantation. Neoral Pediatric Study
      Group.
AB  - At an international meeting held in Madrid, Spain, experience with a new
      microemulsion formulation of cyclosporin A, CyA, (Neoral) in pediatric renal and
      hepatic transplantation was reviewed, with a view to reaching a consensus on
      optimizing its use in these surgical indications. The management of children
      receiving CyA as a post-transplant immunosuppressant is often problematic,
      because CyA absorption from the conventional oral formulation, Sandimmune (SIM),
      is highly variable, bioavailability is low and clearance is particularly rapid in
      this patient population. Key discussion issues included improved absorption
      (reduced variability and greater bioavailability) with Neoral, compared with SIM,
      the suitability of pharmacokinetic parameters and time points for CyA monitoring,
      conversion from SIM to Neoral, twice- vs. three-times-daily therapy and the
      potential to reduce intravenous use of CyA in de novo transplant recipients. It
      was concluded that the favorable pharmacokinetic characteristics of Neoral,
      compared with SIM, are likely to simplify the clinical management of young graft
      recipients and that the consistency of these pharmacokinetic characteristics may
      provide a tool by which immunosuppressive therapy might be improved.

PMID- 10084759
TI  - Living-related small bowel transplantation: the first case in Japan.
AB  - Intestinal failure has been managed with total parenteral nutrition (TPN), but
      occasionally complications such as obliteration of venous access or liver
      dysfunction occur. To overcome such complications, small bowel transplantation
      (SBT) was introduced. Since the introduction of tacrolimus in 1990, successful
      SBT cases have been reported. We performed SBT by using a living donor for a
      child with short bowel syndrome. The recipient (2.5 years old, male) was born
      with intestinal necrosis secondary to midgut volvulus. The length of the
      remaining small bowel was 30 cm. While being managed with TPN, his venous access
      gradually obliterated. Long-term survival could not be expected because of the
      difficulty in securing TPN access. The donor was his mother, whose distal ileum
      (100 cm) was used as a graft. The immunosuppression regimen consisted of
      tacrolimus, steroids and azathioprine. Three episodes of severe rejection and
      subsequent episodes of viral (EBV, CMV) infection were managed with steroid pulse
      therapy and antiviral drugs, respectively. The recipient suffered from
      anastomotic stenosis, and an operation was performed 13 months after
      transplantation to resect the stenotic segment. However, the patient died of
      Pneumocystis carinii pneumonia 16 months after transplantation. We conclude that
      organ retrieval from a living donor can be performed safely for SBT, but further
      study of the management of rejection as well as of viral infection is necessary,
      as it is for non-living-related SBT.

PMID- 10084760
TI  - Cyclosporine-induced white and grey matter central nervous system lesions in a
      pediatric renal transplant patient.
AB  - Major neurologic complications secondary to cyclosporine are well documented and
      are known to include confusion, cortical blindness, seizure, spasticity, paresis,
      ataxia and coma. Most previous reports attribute these to white matter central
      nervous system (CNS) lesions or white/grey matter border lesions. Many
      predisposing factors have been identified, including: elevated levels of
      cyclosporine, hypomagnesemia, hypocholesterolemia, aluminium toxicity, high dose
      steroids, hypertension and infection. However CNS events attributed to
      cyclosporine have been reported without any of these risk factors. We report a
      case of a child developing multiple white and grey matter thalamic and cortical
      lesions along with acute neurologic deterioration, and then review cyclosporine
      mediated CNS injury, including the roles of P-glycoprotein and cyclophilin.

PMID- 10084761
TI  - Does sleep promote recovery after bone marrow transplantation?--A hypothesis.
AB  - Bone marrow transplantation is increasingly being used for treatment of patients
      with malignant and hematologic disorders. The process requires 4-6 wk of waiting
      for recovery from conditioning regimens and for engraftment. Patients undergo
      intensive monitoring and supportive care, yet their requirements for deep
      uninterrupted sleep often go unrecognized. We suggest that deep sleep may promote
      recovery and stem cell proliferation through production of growth hormone and
      melatonin, and through other mechanisms. Growth hormone production occurs
      primarily during deep, rapid-eye-movement (REM) sleep. Growth hormone promotes
      nutritional recovery, mucosal healing, cellular uptake of amino acids, and
      promotes proliferation of bone marrow cell lines in animal models. Melatonin is
      also secreted during nighttime and during sleep. Melatonin increases immune
      response, inhibits tumor growth, counteracts stress-induced immunosuppression,
      protects against viral infections, stimulates GM-CSF, salivary IgA, antioxidant
      properties and enhances sleep. In our preliminary studies, we have found that
      most patients undergoing bone marrow transplantation complain of sleep
      disturbances related to laminar air flow noise-beepers, and lights. We recommend
      several simple methods of enhancing sleep and for more research in the
      pathophysiology of sleep and bone marrow transplantation.

PMID- 10084762
TI  - De novo malignances in pediatric organ transplant recipients.
AB  - A study of 10813 types of cancer that occurred in 10151 organ transplant
      recipients showed that the pattern of malignancies that occurred in pediatric
      recipients was very different from the general pediatric population and from
      adult recipients. Tumors (527) occurred in 512 pediatric patients (aged 18 years
      or less), and 9639 adults developed 10286 neoplasms. Post-transplant
      lymphoproliferative disease (PTLD) was the predominant neoplasm in pediatric
      recipients and comprised 52% of all tumors compared with 15% in adult recipients.
      Eighty-four percent of PTLD in the former patients presented during childhood.
      There was a disproportionately high incidence among nonrenal allograft recipients
      compared with renal recipients (81% vs. 31% of all tumors). The second most
      common malignancy in pediatric patients was skin cancer (19% of tumors), but this
      was less frequent than in adult recipients, in whom it comprised 39% of
      neoplasms. Only 16 pediatric patients (16%) with skin cancers developed their
      tumors during childhood (6 had malignant melanomas), with an average time of
      appearance after transplantation of 126 months (range 5.5-292). Malignant
      melanomas were more common in pediatric than adult recipients (12% vs. 5% of skin
      cancers), as were lip cancers (23% vs. 12%). Spread to lymph nodes was also more
      common in pediatric than in adult recipients (9% vs. 6%). Sarcomas comprised 4%
      of tumors compared with 1% in adults. Carcinomas of the vulva and perineum also
      comprised 4% of tumors. Females outnumbered males in a ratio of 8.5:1. These
      tumors appeared beyond childhood at an average of 142 months (range 42-262
      months) post-transplantation. Other cancers observed in recipients transplanted
      during childhood were thyroid carcinomas (15), Kaposi's sarcomas (15), carcinomas
      of the liver (13), leukemias (13), carcinomas of the cervix (10), brain tumors
      (7), renal carcinomas (7), ovarian carcinomas (5), and miscellaneous tumors (19).
      Of all 527 malignancies, 314 (60%) appeared during childhood and 213 (40%)
      manifested themselves between the ages of 19 and 40 years. By far the most common
      tumor diagnosed during childhood was PTLD, which comprised 230 of the 314 (73%)
      malignancies.

PMID- 10084763
TI  - Growth and quality of life after living-related liver transplantation in
      children.
AB  - Fifty-six consecutive pediatric recipients surviving more than 3 yr after living
      related liver transplantation (LRLT) were evaluated in terms of growth, quality
      of life (QOL) and need for maintenance immunosuppression. Significant improvement
      in Z-score for height and weight were observed at last follow-up, ranging from 3
      to 6 yr after transplantation, although catchup height gain lagged behind
      recovery in weight (height: -1.77 pre-transplant to -0.77 post-transplant,
      p<0.001; weight: -1.12 pre-transplant to -0.18 post-transplant, p<0.0001). 82%
      (46) recipients have remained in good health and have an excellent QOL as
      assessed in the most recent 6 months; these children lead similar daily lives to
      normal healthy children, with daily school attendance and full participation in
      activities including gymnastics and hiking. 3.6% (2) recipients attended school
      regularly but were unable to participate in sporting activities. 14% (8)
      recipients remain home or hospital-bound due to persistent complications in the
      past 6 months, with only minimal school attendance. Less than 10% of recipients
      were taking steroids by 2 yr post-transplantation, although approximately half of
      the children were receiving low-dose maintenance steroids at 1 yr. The mainstay
      immunosuppressant was tacrolimus, with 68% (38) recipients receiving daily
      therapy, 8.9% (5) alternate-day, 8.9% (5) twice a week, and 5.4% (3) a single
      dose weekly or alternate weeks. 7.1% (4) recipients were withdrawn completely
      from all immunosuppressants, including tacrolimus, for various reasons. 8.9% (5)
      patients have needed multiple immunosuppressive agents over the last 6 months. In
      conclusion, LRLT restores growth and offers excellent quality of life in
      pediatric recipients. The majority of recipients require minimal, steroid-free,
      immunosuppression by 2 yr post-transplant, but the occasional recipient still
      needs intensive longterm immunosuppression.

PMID- 10084764
TI  - Growth in children following liver transplantation.
AB  - Although liver transplantation (OLT) has become standard therapy for end-stage
      liver disease in children, growth after OLT remains an area of concern. We
      reviewed our experience with growth after OLT at the Hospital for Sick Children
      in 83 patients who survived at least 1 yr post-transplant. Our aims were to
      describe the success rate in steroid cessation in patients after transplantation,
      to examine the effect of transplantation on subsequent growth, to see if steroid
      reduction had a beneficial effect on growth, and to quantify the risk of stopping
      steroids on rejection. Patients below age 5 yr were weaned off steroids more
      easily than those over age 5: 19.2% vs. 0% (p<0.05), 65.9% vs. 50%, and 79.5% vs.
      37.5% (p<0.05) at post-transplant years 1, 2, and 3, respectively. Pre
      transplant, 30% of patients were below the third percentiles for height and
      weight. Post-transplant, there was a steady improvement in the distribution of
      patients above the 3rd percentile, so that by post-transplant year 6, only 5%
      were below the 3rd percentile. Height and height velocity percentiles were found
      to correlate inversely with total yearly steroid dose (mg/kg) at post-transplant
      years 2, 3 and 6 (p<0.05). In 60% of patients, steroids were successfully
      discontinued. In these patients, height and height velocity percentiles have
      achieved a near normal distribution with 40% and 46% of patients above the 50th
      percentile for height and height velocity percentiles, respectively. No grafts
      were lost to rejection in those off steroids, and all rejection episodes were
      easily reversed. We conclude that the majority of children can be weaned off
      steroids successfully after OLT and that growth in those children in the presence
      of good graft function is near normal.

PMID- 10084765
TI  - The insulin-like growth factor and binding protein axis in children with end
      stage liver disease before and after orthotopic liver transplantation.
AB  - Over 50% of children with established cirrhosis have evidence of growth failure
      and malnutrition. Orthotopic liver transplantation (OLT) is a successful
      treatment for many children and leads to improved growth and nutrition. Most of
      the anabolic actions of GH are mediated through the generation of the mitogenic
      polypeptide insulin-like growth factor-I (IGF-I). Although this is synthesised
      ubiquitously, the bulk of circulating IGF-I is derived from the liver. The
      actions of IGF-I are modulated by a family of at least six high-affinity binding
      proteins (IGFBPs). Growth failure in end-stage liver disease, both before and
      after OLT, may result from abnormalities in the IGF-IGFBP axis. Children who had
      undergone successful OLT were studied before and after OLT. Anthropometry was
      measured by standard techniques. Serum IGFs, IGFBPs and acid labile subunit (ALS)
      were measured by RIA, IRMA, ELISA, Western ligand and immunoblotting. The most
      severely affected anthropometric parameters were skin fold thickness and mid-arm
      circumference. After OLT there was a marked improvement in these parameters.
      Chronic liver disease was characterised by low serum IGF-I, IGF-II, IGFBP-3 and
      ALS levels with raised IGFBP-1 and -2 levels. Serum IGFBP-1 and -2 were
      negatively correlated with pre-OLT anthropometric parameters. After OLT, there
      was a rapid normalisation of serum IGF-I, while IGF-II and IGFBP-3 overshot to
      supranormal levels. ALS levels post-OLT remained below control levels. By 3 years
      post-OLT, IGFBP-3 had fallen to levels which were insignificantly different from
      controls. IGFBP-1 fell but remained above normal, while there was no significant
      change in IGFBP-2. Growth post-OLT correlated positively with serum IGF-I and
      negatively with IGFBP-1. In conclusion, chronic liver disease is associated with
      marked changes in body composition. These changes are associated with and may be
      caused by an impaired generation of IGF-I and altered production of IGFBPs. After
      OLT there is a marked improvement in growth associated with partial normalisation
      of the IGF-IGFBP axis. However, there are persistent abnormalities in this axis
      which may explain growth failure post-OLT.

PMID- 10084766
TI  - Health-related quality of life after organ transplantation in childhood.

PMID- 10084767
TI  - Young cadaver donors should not be used for young recipients!

PMID- 10084768
TI  - Should pediatric kidneys be used for pediatric patients?

PMID- 10084769
TI  - Cancers after stem cell transplantation in children: a cost of cure?
AB  - There have been many advances in the field of stem cell transplantation over the
      past few years. Newer preparative regimens and better supportive care measures
      are allowing more children to survive and lead long lives after stem cell
      transplantation. We are only now beginning to see what the cost of this success
      may be in regard to the long-term effects of this treatment. Most long-term
      follow up studies have been reported in the adult literature and there is very
      little information on the pediatric population. Children who undergo stem cell
      transplantation will have a long period of observation in which new and different
      complications can occur. This article looks at the current literature on
      secondary malignancies and lymphoproliferative disorders after stem cell
      transplantation in children, with particular focus on risk factors, possible
      strategies for prevention, and treatment.

PMID- 10084770
TI  - Small bowel transplantation in children.
AB  - Small bowel transplantation has become a life-saving procedure for selected
      adults and children with intestinal failure who are intolerant to parental
      nutrition. There are few pediatric data available on the results of this
      procedure. In this article we review the background of intestinal
      transplantation, present the results from the University of Western Ontario in
      London, Ontario and the University of Miami in Miami, Florida, and discuss some
      future directions. The majority of successful transplants are fully functional,
      and these children are able to assume a normal diet.

PMID- 10084771
TI  - Renal transplantation from donors aged < 6 years into children yields equal graft
      survival when compared to older donors.
AB  - Several articles have shown inferior renal allograft survival in patients
      receiving kidneys from young cadaver donors. We therefore assessed the survival
      and function of the first cadaveric graft from donors aged under 6 years of age,
      transplanted after 1983. The results were compared with the outcome of children
      receiving kidneys from older donors. Graft survival and serum creatinine were
      analyzed retrospectively at various time intervals after first cadaveric
      transplantation in 35 pediatric recipients of renal transplants grafted between
      1983 and 1996 from donors < 6 years of age. Their data were compared with those
      of 167 pediatric recipients of renal transplants grafted from older donors. The
      proportion of young donors remained constant throughout the observation period.
      Mean recipient age was 10.4 years (range 3.2-17.5 years) in the patients grafted
      from donors < 6 years of age, not much different from the mean age of the donors
      in the 6+ years group (12.5 years, range 2.3-18.6 years). Five-year patient
      survival did not differ between the two groups (89 vs. 90%). In 1983-1996, graft
      survival rate of kidneys from donors aged < 6 years after one year was 77%
      (donors aged 6+ years=76%), after 2 years 66% (donors aged 6+ years=68%), after 3
      years 62% (donors aged 6+ years=66%), and after 5 years 55% (donors aged 6+
      years=60%, n.s., Log-rank test). In 1994-1996, 2-year graft survival was 88%
      (controls 91%, n.s.). In children receiving a cadaveric graft from a donor aged <
      6 years, mean serum creatinine fell from 132+/-101 (SD) micromol/l after 3 months
      to 101+/-66 micromol/l after 12 months, and was 110+/-52 micromol/l after 5
      years. This compared with a serum creatinine of 131+/-108 micromol/l after 3
      months, 132+/-97 micromol/l after 12 months and 143+/-81 micromol/l after 5 years
      in children receiving grafts from older donors. When transplanting renal
      allografts from young donors into children, there was no significant difference
      in graft survival between donors aged < 6 years and older donors or in graft
      function. We conclude that good results from young donors can be obtained in a
      specialized center, and therefore the restriction of kidney selection to donors
      aged > 6 years may not be justified.

PMID- 10084772
TI  - Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive
      fungal infections in children undergoing organ or allogeneic bone-marrow
      transplantation.
AB  - Sixty-one children with a median age of 6 years (range 1-16) were given
      prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin
      (AmBisome) and were reviewed retrospectively. Thirty-six received allogeneic bone
      marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney. AmBisome was
      given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal
      infections (IFI) in 33 and for a verified IFI in 15. AmBisome prophylaxis was
      given for a median of 14 days in a dose of 1 mg/kg/day. The median dose of
      AmBisome was 2.1 mg/kg/day (range 0.9-5.0). The median duration of therapy was 10
      days in children with suspected IFI and 20 days in children with verified IFI.
      The total dose ranged from 0.025 g up to a maximum of 3.95 g. Proven and probable
      side effects of AmBisome were a decrease in the level of serum potassium (30/78
      cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back
      pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in
      the bilirubin level (1), nausea (1), chest pain (1) and fever (1). Of 31 children
      with suspected IFI, fever disappeared in 21 (68%). In 14 verified or suspected
      IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%).
      Eradication of fungi from a deep site was verified in 8/10 and the survival rate
      from 1 1/2 years to more than 7 years was 7/12 (58%). We conclude that AmBisome
      was well tolerated as prophylaxis and therapy in transplanted children, few acute
      toxic side effects were seen and the cure rate in verified IFI was high.

PMID- 10084773
TI  - Health-related quality of life after organ transplantation in childhood.
AB  - While sophisticated data on patient and graft survival are available, very little
      is known about the overall health-related quality of life (HRQOL) after organ
      transplantation (Tx) in childhood. We examined the perceived HRQOL of survivors
      of heart, liver and kidney Tx. A previously validated, age-appropriate,
      multidimensional questionnaire was completed by 59 survivors, currently aged 8-23
      years, who had received an organ transplant in 1983-1994, at least 6 months prior
      to the study. The overall HRQOL score of the patients aged 8-11 was lower than
      that of the normal controls, while the HRQOL scores of the patients aged 12-15
      and 16-23 were similar to those of the controls. However, the younger patients
      had more complex diseases. Compared to the controls, the patients reported more
      problems regarding their mobility, usual activities, and school and hobbies. In
      addition, the patients aged 8-11 reported more problems with eating, elimination,
      friends and ability to concentrate than the controls. There was an association
      between age at Tx and HRQOL, but no association between the type of Tx or time
      since Tx and HRQOL. The perceived emotional status of the patients was better
      than that of the controls, especially during and after adolescence. We conclude
      that to provide optimal care, patients HRQOL should be assessed. Although the
      survivors report problems, the overall HRQOL after Tx is good. The occurrence of
      complications before Tx appears to be a crucial factor as regards the long-term
      HRQOL of the survivors. Attention should be paid to treatment prior to Tx and to
      the timing of Tx in order to improve the HRQOL after Tx.

PMID- 10084774
TI  - Psychological and social adjustment after pediatric liver transplantation as a
      function of age at surgery and of time elapsed since transplantation.
AB  - The study assessed psychological and social adjustment to pediatric liver
      transplantation in 101 patients aged 4-16 years who had undergone transplantation
      2-10 years earlier. Each parent completed the Child Behavior Check List (CBCL)
      independently and answered a transplantation questionnaire assessing psychosocial
      issues. Most children scored within the normal range for both parts of the CBCL
      (i.e. Behavioral Problems and Social Competences). The impact of age at
      transplantation and of time elapsed since transplantation were examined. Earlier
      transplantation was associated with subsequent higher scores for Aggressive
      Behavior and Sex Problems, with lower scores for Activities and Competences, and
      with more parental anxiety concerning their child's health. The longer the time
      elapsed since transplantation, the more mothers rated high levels on the Somatic
      complaints, Anxiety/depression, Competence, and Social activity CBCL scales for
      their child. Parents reported talking more about the transplantation with their
      children with increasing time following transplantation. This suggests that
      transplantation remains an important event even after long periods of time from
      the transplant event. Finally, despite the difficulties encountered, more than
      80% of the parents considered the transplantation had been beneficial to their
      child.

PMID- 10084775
TI  - Renal transplantation in children from 1987-1996: the 1996 Annual Report of the
      North American Pediatric Renal Transplant Cooperative Study.
AB  - The 1996 Annual Report of the North American Pediatric Renal Transplant
      Cooperative Study (NAPRTCS) summarizes data voluntarily collected from 130
      centers on 4329 children and adolescent patients who received renal transplants
      on or after January 1, 1987. This report updates information on transplants; data
      on dialysis and chronic renal insufficiency have, for the first time, been
      reported separately (in submission). The NAPRTCS registry shows that the majority
      of pediatric renal transplants are performed in children above 6 years of age
      (73%). The most frequent diagnoses include obstructive uropathy (16%),
      aplastic/hypoplastic/dysplastic kidneys (16%), and focal segmental
      glomerulosclerosis (12%). Pre-emptive transplantation was performed in 24% of
      patients. Triple drug maintenance therapy with prednisone, cyclosporine and
      azathioprine was used by >70% of all transplant recipients throughout 7 years of
      follow-up. Fifty-six per cent of transplant recipients were rehospitalized during
      months 1-5 (51% live donor (LD), 62% cadaver donor (CD)), with rejection and
      infection as the main causes. In the period 30-35 months post-transplant, 19-22%
      of patients (163 LD, 185 CD) were rehospitalized. The median time to the first
      rejection was 46 days for CD transplants and 377 days for LD grafts (p<.001). Six
      year graft survival rates were 73% and 56% for LD grafts and CD grafts,
      respectively (p<.001). The overall growth deficit was constant over a period of
      60 months. However, children transplanted under 5 years of age reduce their
      height deficit by about one-third compared to an increase in height deficit of up
      to 22% for older children. The NAPRTCS data analysis also demonstrates a delay in
      first rejection episodes in LD compared to CD transplants, and a steady
      improvement in CD graft survival over the past 5 years in pediatric transplant
      recipients.

PMID- 10084776
TI  - Pediatric transplant grand rounds. A case presentation: skin lesions in a post
      lung transplant patient.

PMID- 10084777
TI  - Growth factors in children with end-stage liver disease before and after liver
      transplantation: a review.
AB  - Growth failure is a common observation in children with end-stage liver disease
      (ESLD). The liver is an important endocrine organ producing potent anabolic
      growth factors such as IGF-I (insulin-like growth factor-I) and its major binding
      proteins, called IGFBP-1, -2 and -3. Circulating IGF-I and IGFBP-3 levels are low
      in children with chronic liver failure despite increased GH secretion. This
      discrepancy suggests that GH resistance is present in chronic liver failure and
      is mainly due to the associated malnutrition. The advent of orthotopic liver
      transplantation (OLT) has dramatically improved the life expectancy of children
      with ESLD. Nevertheless, the growth of 15-20% of the children in recent studies
      remains poor after successful transplantation. Several factors such as age and
      height deficit at the time of OLT, etiology of the liver disease and graft
      function as well as the dose and mode of administration of glucocorticoids have
      been implicated in the lack of complete catch-up growth following surgery. Few
      studies have explored the possibility that anomalies in the GH-IGF-I cascade
      could explain growth retardation. However, it is unlikely that major anomalies of
      the GH-IGF-I axis contribute to impaired growth. Treatment with GH alone or in
      combination with IGF-I before or after OLT may improve the growth of children.
      Randomized multi-center studies are needed to address this issue.

PMID- 10084778
TI  - Factors affecting growth and strategies for treatment in children after renal
      transplantation.
AB  - Growth failure is a frequent side effect of long-term high-dose glucocorticoid
      therapy in children. Pharmacological doses of glucocorticoids interfere at
      different levels with the integrity of the somatotropic hormone axis. The
      majority of patients on chronic corticosteroid medication present with overt GH
      hyposecretion, apparently due to enhancement of hypothalamic somatostatin
      release. Glucocorticoids also inhibit IGF bioactivity by the induction of IGF
      inhibitors and stimulate the production of certain IGFBPs. In addition,
      glucocorticoids inhibit growth directly at the tissue level by suppressing local
      growth factors and skeletal tissue matrix production. In children post renal
      transplantation, concomitant treatment with cyclosporin A for immunosuppression
      allows low-dose glucocorticoid medication. Reduction of glucocorticoids, in
      particular when given as alternate-day therapy, improves growth in some but not
      all children. The new glucocorticoid deflazacort appears to have fewer side
      effects regarding steroid-induced osteopenia and cushingoid appearance. A
      beneficial effect on longitudinal growth has not been clearly established. Recent
      experimental and clinical data indicate that the catabolic and growth-depressing
      effects of glucocorticoids can be counterbalanced by concomitant anabolic
      treatment with rhGH. The potential role of rhIGF-I is less well investigated.
      Treatment with rhGH is able to antagonize several side effects of long-term
      glucocorticoid administration, such as growth failure, protein-wasting and
      osteoporosis. If catch-up growth cannot be achieved by an alternate-day steroid
      regimen and discontinuation of glucocorticoids appears to be an intolerable risk
      for graft survival, rhGH therapy may be initiated. However, rhGH therapy in this
      setting must still be considered experimental, because the possible interference
      of rhGH with the immunosuppressive action of glucocorticoids in children after
      organ transplantation is still incompletely defined.

PMID- 10084779
TI  - Interactions between glucocorticoids and the growth hormone-insulin-like growth
      factor axis.
AB  - Glucocorticoids in pharmacological doses interfere with the integrity of the
      somatotropics hormone axis. However, the apparent discrepancies between the in
      vitro and in vivo studies, short-term vs. long-term exposure, and species
      specific changes complicate a clear assessment of these interactions. The growth
      depressing effects of glucocorticoids are multifactorial and involve suppression
      of pituitary GH release by stimulating hypothalamic somatostatin tone, down
      regulation of hepatic GH receptors, inhibition of GH bioactivity by the induction
      of IGF inhibitors, complex alteration of the IGFBP serum profile, and a direct
      suppressive effect on tissue matrix production and synthesis of local growth
      factors.

PMID- 10084780
TI  - Impact of growth hormone treatment on a Belgian population of short children with
      renal allografts.
AB  - We retrospectively analyzed the effects of recombinant human growth hormone
      (rhGH) in a Belgian population of 36 short children with renal allografts. Seven
      children were dropped from the growth study: 1 had skeletal dysplasia and in 6
      cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were
      non-compliant and 2 grafts deteriorated). Final height was reached in 17
      patients, and 12 children were still growing at the end of the study. Median
      height standard deviation score (SDS) in the 29 patients was -2.3 at the time of
      transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy
      (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4
      per year, and bone maturation was not accelerated. Final height reached was 162.7
      (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median
      SDS -1.9) in females. Final height is significantly greater in males than females
      compared with a historical control group of untreated patients. Final height is
      within the parental target height range in 6 out of the 17 patients. The increase
      in height SDS in patients who were at an advanced stage of puberty (Tanner stages
      4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain
      14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients
      developed an acute allograft rejection, all of whom had an underlying chronic
      rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that
      rhGH treatment has a positive effect in short children with renal allografts,
      even if it is started in late puberty. In the presence of underlying chronic
      rejection, rhGH treatment needs careful monitoring to minimize the risk of graft
      loss.

PMID- 10084781
TI  - Optimal management of renal failure in primary hyperoxaluria in infancy, and the
      use of combined kidney/liver transplantation.

PMID- 10084782
TI  - 15 years of pediatric heart transplantation at the University of Pittsburgh:
      lessons learned and future prospects.
AB  - Credit for the first pediatric heart transplant is given to Kantrowitz and
      colleagues who, in 1967, transplanted the heart of an anencephalic infant into a
      3-week-old with tricuspid atresia (1). Although the infant only survived a few
      hours after surgery, this pioneering procedure emphasized the technical
      feasibility of heart transplantation in childhood. Over the next decade,
      enthusiasm for heart transplantation declined in both adults and children, as it
      became apparent that the therapeutic armamentarium for controlling acute
      allograft rejection was inadequate for achieving graft and patient survival.
      Towards the end of the 1970s, several advances led to renewed interest in human
      heart transplantation. These included topical cooling of the donor heart to
      protect the myocardium from ischemia (and enabling distant procurement), the
      technique and interpretation of endomyocardial biopsy for the diagnosis of
      allograft rejection (2) and, most importantly, the introduction of cyclosporine
      into human clinical trials (3). Cyclosporine was the first oral agent
      specifically to inhibit T lymphocytes, the principal mediators of allograft
      rejection. The favorable impact on survival of adult heart transplant recipients
      was immediately apparent (4) and led to renewed interest in pediatric heart
      transplantation. The pediatric heart transplant program at the University of
      Pittsburgh commenced in 1982, drawing on the experience of the adult program
      which had begun two years earlier. It rapidly became apparent that children
      present unique problems for the transplant physician and surgeon. This review
      draws on many of the lessons learned in our program over the last 15 years and
      reviews some of the prospects for the future of pediatric thoracic organ
      transplantation.

PMID- 10084783
TI  - Pre-transplant blood transfusion and renal allograft outcome: a report of the
      North American Pediatric Renal Transplant Cooperative Study.
AB  - Data from the North American Pediatric Renal Transplant Cooperative Study were
      analyzed to determine the effect of pre-transplant blood transfusions on graft
      survival and acute rejection for pediatric renal transplant recipients. Between
      January 1, 1987 and November 11, 1995, 4015 renal transplants in children <18
      years of age (2007 living donor, 2008 cadaver) were registered in the study.
      Recipients were grouped by number of pre-transplant blood transfusions (0,
      n=1171; 1-5, n=1796; >5, n=1048). The risks of graft failure and acute rejection
      were related to number of pre-transplant transfusions by proportional hazards
      regression analysis. Models were adjusted for recipient age, sex, race, induction
      therapy, prior dialysis, prior transplant, HLA-DR mismatching, and transplant
      year. Additionally, the living donor (LD) model was adjusted for the use of donor
      specific blood transfusion, and the cadaver donor (CAD) model was adjusted for
      donor age and cold storage time. The risk of graft failure was increased in LD
      (p<0.001) and CAD (p=0.001) recipients who received >5 pre-transplant
      transfusions. There was no significant difference in the causes of graft loss
      between groups. The risk of a first acute rejection decreased in LD recipients
      who received 1-5 blood transfusions compared with 0 (p=0.04) or >5 (p=0.003) and
      in CAD recipients who received 1-5 compared with 0 (p=0.05). We conclude that
      multiple (>5) pre-transplant blood transfusions are a risk factor for graft
      failure in pediatric recipients and should be avoided. However, limited blood
      transfusions (1-5) are associated with a decreased risk of acute rejection. Our
      data show that for pediatric recipients the number of pre-transplant blood
      transfusions is an important factor in transplant outcome.

PMID- 10084784
TI  - A prospective trial of steroid cessation after renal transplantation in pediatric
      patients treated with cyclosporine and mizoribine.
AB  - We conducted a multi-center prospective study to evaluate the safety and efficacy
      of steroid withdrawal after renal transplantation in children. In 52 children (51
      living-related donor transplants and 1 cadaver donor transplant),
      immunosuppressive therapy was started with cyclosporine (CyA), mizoribine (MZ),
      methylprednisolone (MPL) and anti-lymphocyte globulin. Administration of MPL was
      reduced to alternate days more than 6 months after transplantation, and attempts
      were made to withdraw it. Acute rejection was noted in 19 patients (36.5%) by 1
      month after transplantation. The whole-blood CyA trough level using monoclonal
      antibody was 175.0+/-17.0 ng/ml in patients who developed acute rejection and
      282.0+/-25.3 ng/ml in those who did not show acute rejection (p<0.01). During the
      37 attempts at alternate-day MPL administration, clinical acute rejection was
      observed in only 1 patient and chronic rejection in 3. During 10 attempts to
      withdraw MPL, acute rejection was noted in 3 patients, but graft function
      recovered to the pre-rejection level after treatment of the acute rejection. At
      the last observation, graft function was lost in 3 patients, 22 were receiving
      MPL on alternate days, and MPL had been withdrawn from 7 for a mean period of
      16.7 months. The survival rate of the patients and the grafts was 100% and 94%
      after an average follow-up period of 4 years. Evaluation of growth showed catch
      up growth in all patients during the withdrawal period.

PMID- 10084785
TI  - Varicella in the first year after renal transplantation: a report of the North
      American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Prior reports document that children with renal transplants are at risk of severe
      varicella, with a 5-25% mortality rate. We have examined the current incidence
      and mortality of varicella requiring hospitalization in pediatric patients in the
      first year after kidney transplantation through a multi-center retrospective
      cohort study. Data from the North American Pediatric Renal Transplant Cooperative
      Study (NAPRTCS) for 2320 pediatric patients who received renal transplants
      between 1987 and 1993 and were followed until 1995 were examined. Varicella
      requiring hospitalization in the first post-transplant year occurred in 44
      children. Characteristics of the patients who developed varicella were compared
      to the rest of the NAPRTCS cohort using chi-square analysis. Kaplan-Meier
      estimates of graft survival were used to compare graft survival in varicella
      patients and other NAPRTCS patients. Varicella patients tended to be younger
      (p=0.09) and more often male (p=0.07, chi-square) than other NAPRTCS patients.
      None of the 44 patients with varicella in their first post-transplant year died
      from this infection. The number of episodes of acute rejection per transplant and
      the time to first rejection was not different in patients with varicella compared
      to the other NAPRTCS patients. Five-year graft survival was not different for
      varicella cases when compared to other NAPRTCS patients with grafts surviving at
      least 6 months post-transplant. We conclude that the mortality rate of patients
      hospitalized with varicella in the first post-transplant year and the risk of
      subsequent graft dysfunction may be significantly lower than previously
      described. However, varicella remains a significant cause of potentially
      avoidable hospitalization in the first post-transplant year. Further study of the
      safety and efficacy of varicella vaccination in children with renal insufficiency
      and those post-transplant is warranted.

PMID- 10084786
TI  - Primary vascular thrombosis after renal transplantation in children.
AB  - The aim of the study was to assess the incidence, causes, diagnostic and
      treatment modalities, and outcome of vascular thrombosis after kidney
      transplantation in children. Between 1984 and 1995 we performed 176 kidney
      transplants in pediatric recipients aged 1 to 18 years. Vascular thrombosis
      followed 7 transplants, 4 were renal vein and 3 arterial thromboses. Venous
      thromboses occurred 2 to 12 days after transplantation. All of the patients with
      a renal vein thrombosis lost their grafts. Arterial thrombosis developed in 2
      cases of double renal arteries which were separately anastomosed into the
      recipient vessels. One graft was lost, but the other was saved by thrombolytic
      therapy (streptokinase). One child experienced intrarenal segmental artery
      thrombosis during acute vascular rejection, which resolved following combined
      anti-rejection and thrombolytic (intra-arterial streptokinase) treatment with
      full recovery of graft function. In all, vascular thrombosis complicated 7 out of
      176 transplants (4.0%), and was the cause of 5 graft losses (2.8%). The incidence
      of vascular thrombosis was not increased in grafts with vascular anomalies (3/34
      v. 4/142; p>0.05, chi sq.). We conclude that acute tubular necrosis, rejection
      and unstable volemia may predispose to vascular thrombosis. In selected cases,
      early diagnosis of vascular thrombosis may enable graft salvage by surgical or
      thrombolytic treatment.

PMID- 10084787
TI  - Diagnosis and management of primary hyperoxaluria type 1 in infancy.
AB  - We report a case of a 6-month-old infant who presented with failure to thrive due
      to end-stage renal disease as a result of primary hyperoxaluria type 1. The
      infant was managed with a combined daily hemodialysis and peritoneal dialysis
      prescription in order to manage the total body oxalate burden. Medical management
      included oral pyridoxine, aggressive hydration and nutritional supplementation
      via an enteral feeding tube. At one year of age the infant underwent a combined
      liver/kidney transplantation with intra- and daily post-operative hemodialysis to
      prevent oxalate deposition in the newly transplanted organs. The post-operative
      course was complicated by gross hematuria and increased hyperoxaluria, requiring
      an increase in hydration and thiazide diuretics. This infant received a
      combination of dialysis modalities which was designed to lower the potential
      oxalate burden prior to transplantation. This case illustrates the difficulty in
      medical management of an infant pre- and post-combined liver/kidney
      transplantation.

PMID- 10084788
TI  - Pediatric renal transplantation: a review of the UNOS data. United Network for
      Organ Sharing.
AB  - The UNOS Scientific Renal Transplant Registry data from October 1987 to December
      1996, including information on transplants to 537 patients aged 0-2, 2399
      patients aged 3-12 and 5986 patients aged 13-21, were used to examine the results
      of pediatric transplantation by both univariate and multivariate methods. One
      year and long-term graft survival rates were adjusted for 9 covariates including
      donor source and age, recipient sex, race and disease, and transplant year, HLA
      mismatches, and transplant center. The adjusted 1- and 5-year graft survival
      rates were 71% and 60% for ages 0-2, 83% and 64% for ages 3-12 and 85% and 57%
      for ages 13-21. Except for the youngest recipients, these results compared
      favorably at 1 year with 86% graft survival among 78,418 adults. The projected
      graft half-life was highest in patients under age 2 (18 years) and lowest among
      teenagers (7 years) compared with adults and children (11 years). Univariate
      analyses revealed a significant 10% graft survival advantage with living donor
      kidneys for all age groups, but especially for those aged 0-2 in whom survival
      was 66% with a cadaver donor and 84% with a living donor. The youngest recipients
      experienced early rejection of the mother's kidney less often than the father's
      (47% vs 28% in the first 6 months, p<0.007). Results in blacks were similar to
      those in whites during the first year, but the 3.8 year half-life for black
      teenagers was the lowest among all groups. We conclude that with the exception of
      very young (age 2 or under) patients, 1-year pediatric renal transplant survival
      rates are comparable to those in adults, but in the long term, non-compliance and
      late acute rejection result in an accelerated graft failure rate among teenagers.

PMID- 10084789
TI  - Pediatric transplant grand rounds.

PMID- 10084790
TI  - Resistance to growth hormone in children with chronic liver disease.
AB  - Malnutrition adversely affects mortality and morbidity before and after liver
      transplantation. Outcome might be improved if liver transplant recipients were in
      a better nutritional state at the time of transplantation. In this review, we
      will examine the potential use of GH and IGF-I to improve nutritional status in
      patients with cirrhosis. Patients with cirrhosis have low circulating IGF-I
      levels in the face of elevated serum GH concentrations. IGFBP-3 levels are low
      while IGFBP-1 levels are high. In patients with cirrhosis, IGF-I levels do not
      increase in response to treatment with GH. Patients with cirrhosis are
      insensitive to GH, and rhGH treatment is not likely to reverse malnutrition. The
      pathobiology of GH insentivity may reflect decreased nutritional intake, low GH
      receptor density, decreased IGF-I half-life and hepatic insensitivity to insulin.

PMID- 10084791
TI  - Nutritional factors affecting growth before and after liver transplantation.
AB  - Malnutrition is present in approximately 60% of children at the time of liver
      transplantation. The pathogenesis of malnutrition is complex and includes reduced
      calorie intake, fat malabsorption, abnormal nitrogen metabolism, and increased
      energy expenditure leading to increased calorie requirements. As nutritional
      status at transplantation is a significant factor in both morbidity and mortality
      post liver transplantation, intensive nutritional support pre-transplant is vital
      and may be achieved with a modular feed providing 120-150% estimated average
      requirement (EAR). Approximately 80% of children who survive liver
      transplantation will achieve normal growth and nutritional status within 12
      months post-transplant. Significant factors responsible for growth failure post
      transplant include pre-operative nutritional status (height SDS score <-2),
      continued glucocorticoid administration, recurrent hepatic dysfunction or chronic
      rejection and reduced calorie intake due to behavioural feeding problems.
      Effective future strategies include intensive pre- and post-operative nutritional
      support and early reduction of glucocorticoid administration.

PMID- 10084792
TI  - Growth post renal-transplantation in children: lessons from the North American
      Pediatric Renal Transplant Cooperative Study (NAPRTCS).
AB  - Growth retardation following successful transplantation has been noted since the
      availability of ESRD care for children more than a quarter of a century ago.
      During the past decade, data collection and analysis of the NAPRTCS data base
      have detailed the factors which have an impact on growth in renal allograft
      recipients transplanted in the cyclosporine era. These analyses have led to the
      following conclusions. 1. Standardized height (z score) worsens in the majority
      of pediatric recipients following renal transplantation. 2. Catch-up growth
      (improvement in standardized height) occurs primarily in recipients <6 years of
      age at transplantation. Therefore, age at transplantation is a significant factor
      determining the magnitude of post-transplant growth. 3. Reduced allograft
      function has a profound negative impact on growth following transplantation. 4.
      Height deficit at the time of transplantation correlates with increment in height
      following transplantation. The most profoundly growth-retarded recipients exhibit
      the greatest increase in standardized height. 5. Race has been identified by
      NAPRTCS as a factor affecting post-transplant growth. Caucasian recipients
      exhibit a greater improvement in standardized height compared to African-American
      and Hispanic recipients. 6. Since serial evaluation of NAPRTCS data indicates
      that catch-up growth is unlikely to occur in 75% of renal allograft recipients,
      strategies such as the use of growth hormone would be advantageous in the future.

PMID- 10084793
TI  - The effect of rhGH in vitro on donor-specific hyporesponsiveness in pediatric
      transplantation.
AB  - Recombinant human growth hormone (rhGH) improves growth in children after renal
      transplantation, but may be associated with augmented immune responses. To
      understand the effect of rhGH in transplantation, we evaluated the role of rhGH
      in a mixed leukocyte culture (MLC) in vitro. We demonstrated that PBMC isolated
      from normal adult volunteers cultured in an MLC in the presence of rhGH develop
      an augmented proliferative (25-400%) and cytotoxic (50-600%) response. Using in
      situ hybridization (ISH), we demonstrated that the frequency of cells expressing
      mRNA for IFNgamma increased in the presence of rhGH (100-800%). In vitro
      responses of PBMC from adults in an MLC may only loosely reflect responses in
      vivo during pediatric transplantation. After transplantation, adults develop
      decreased responses to donor-specific antigens in an MLC (donor-specific
      hyporesponsiveness - DSH). We evaluated the donor-specific responses of 20
      pediatric patients who had each received a renal allograft from one parent.
      Pediatric patients developed DSH similarly to adults; however, no correlation was
      seen between the amount of DSH and graft function. We also evaluated the
      expression/production of IFNgamma and IL4 in response to donor-specific
      alloantigens. Patients exhibit marked DSH of IFNgamma expression and production.
      However, IL4 production was seen in 8 out of 10 patients with normal renal
      function, but only 1 out of 7 patients with biopsy proven chronic rejection.
      Finally, we evaluated the effect of rhGH in vitro on DSH. Only 3 out of 20
      patients developed augmented donor-specific responses in the presence of rhGH in
      vitro. rhGH augments proliferation, cytotoxicity and IFNgamma expression during
      an MLC. After renal transplantation, rhGH augments donor-specific responses
      during an MLC in some pediatric patients.

PMID- 10084794
TI  - Antigen recognition.

PMID- 10084795
TI  - Cytoskeleton. Web alert.

PMID- 10084797
TI  - Off the record.

PMID- 10084796
TI  - Belief and behavior.

PMID- 10084798
TI  - Improving intra-oral radiography.

PMID- 10084799
TI  - James E. Oldfield. Recipient of the Klaus Schwarz Award for 1998.

PMID- 10084800
TI  - World transplant records--1997.

PMID- 10084801
TI  - Worldwide Transplant Center directory. Kidney transplants.

PMID- 10084802
TI  - Worldwide Transplant Center directory. Bone marrow transplants.

PMID- 10084803
TI  - Worldwide Transplant Center directory. Peripheral blood stem cell transplants.

PMID- 10084805
TI  - Worldwide Transplant Center directory. Heart/lung transplants.

PMID- 10084804
TI  - Worldwide Transplant Center directory. Heart transplants.

PMID- 10084806
TI  - Worldwide Transplant Center directory. Lung transplants.

PMID- 10084807
TI  - Worldwide Transplant Center directory. Liver transplants.

PMID- 10084808
TI  - Worldwide Transplant Center directory. Pancreas transplants.

PMID- 10084809
TI  - Worldwide Transplant Center directory. Kidney/pancreas transplants.

PMID- 10084811
TI  - Worldwide Transplant Center directory. Small bowel transplants.

PMID- 10084810
TI  - Worldwide Transplant Center directory. Multiorgan transplants.

PMID- 10084812
TI  - Worldwide Transplant Center directory. Islet transplants.

PMID- 10084813
TI  - Worldwide Organ Procurement Organization directory.

PMID- 10084814
TI  - Mitochondrial disorders.

PMID- 10084815
TI  - Hepatitis C virus infection in patients with overt B-cell non-Hodgkin's lymphoma
      in a French center.

PMID- 10084816
TI  - The adverse influence of pretransplant interferon-alpha (IFN-alpha) on transplant
      outcome after marrow transplantation for chronic phrase chronic myelogenous
      leukemia increases with the duration of IFN-alpha exposure.

PMID- 10084817
TI  - Successful modification of a pp65 antigenemia-based early treatment strategy for
      prevention of cytomegalovirus disease in allogeneic marrow transplant recipients.

PMID- 10084818
TI  - Cimetidine activates interleukin-12, which enhances cellular immunity.

PMID- 10084819
TI  - Analytical biotechnology. Web alert.

PMID- 10084820
TI  - Distribution and functional anatomy of amine-containing neurons in decapod
      crustaceans.
AB  - One of the lessons learned from studying the nervous systems of phylogenetically
      distant species is that many features are conserved. Indeed, aminergic neurons in
      invertebrate and vertebrate systems share a multitude of common characteristics.
      In this review, the varied roles of serotonin, octopamine, dopamine, and
      histamine in decapod crustaceans are considered, and the distributions of the
      amine-containing cells are described. The anatomy of these systems reinforces the
      idea that amine neurons are involved in widespread modulation and coordination
      within the nervous system. Many aminergic neurons have long projections, linking
      multiple regions with a common input, and therefore are anatomically perfected as
      "gain setters." The developmental patterns of appearance of each amine in the
      crustacean nervous system are described and compared. The developmental picture
      suggests that transmitter acquisition is distinctive for each amine, and that the
      pace of acquisition may be co-regulated with target maturation. The distinctive
      roles that transmitters play during specific developmental periods may,
      ultimately, provide important clues to their functional contributions in the
      mature organism.

PMID- 10084821
TI  - Histamine in the brain of insects: a review.
AB  - Histamine is the neurotransmitter of photoreceptors in insects and other
      arthropods. As a photoreceptor transmitter, histamine acts on ligand-gated
      chloride channels. Another type of histamine receptor has been indicated in the
      insect central nervous system by binding pharmacology. This receptor is similar
      to the mammalian H1 receptors, which are G-protein coupled and thus utilize a
      second messenger system. The distribution of histamine-immunoreactive (HAIR)
      neurons has been studied in a few insect species: cockroaches, locust, crickets,
      honey bee, blowflies, and in Drosophila. In addition to its presence in
      photoreceptor cells, histamine is distributed in a rather small number of neurons
      in the insect brain. Many of these neurons have extensive bilateral arborizations
      that innervate several distinct neuropil regions, notably in the protocerebrum.
      Some patterns of histamine distribution are seen in all the species. On the other
      hand, the number and morphology of neurons differ between the studied species,
      and several major neuropils (central body, antennal lobes, mushroom bodies) are
      supplied by HAIR neurons in some species, but not in others. Thus it appears that
      there are some species-specific functions of histamine and on others that are
      preserved between species. Some of the histaminergic neurons may constitute wide
      field inhibitory systems with functions distinct from those of neurons containing
      gamma-amino butyric acid (GABA). Novel data are presented for Drosophila and the
      cockroach Leucophaea maderae and a comparison is made with published data on
      other insects.

PMID- 10084822
TI  - Cytoarchitecture of histamine-, dopamine-, serotonin- and octopamine-containing
      neurons in the cricket ventral nerve cord.
AB  - The present article provides a comparative neuroanatomical description of the
      cellular localization of the biogenic amines histamine, dopamine, serotonin and
      octopamine in the ventral nerve cord of an insect, namely the cricket, Gryllus
      bimaculatus. Generally, different immunocytochemical staining techniques reveal a
      small number of segmentally distributed immunoreactive (-IR) amine-containing
      neurons allowing single cell reconstruction of prominent elements. Aminergic
      neurons share common morphological features in that they innervate large portions
      of neurophil and often connect different neuromeres by intersegmental 'wide
      field' projections of varicose appearance. In many cases aminergic terminals are
      also found on the surface of peripheral nerves suggesting additional neurohemal
      release sites. Despite such morphological similarities histological analysis
      demonstrates for any given amine functionally distinct neuron types with specific
      innervation patterns establishing discrete pathways. Histamine-IR interneurons
      are characterized by both ascending and descending projections forming central
      and peripheral terminals. The descending branches from dopamine-IR cells mainly
      converge within the terminal ganglion, whereas serotonin-IR interneurons with
      ascending projections often terminate within the brain. Serotonin is also present
      in sensory and motor neurons. In contrast to other aminergic neurons, most
      octopamine-IR cells represent unpaired neurons projecting through motor nerves of
      the soma-containing neuromere. Octopamine-IR cells with intersegmental branches
      are only rarely found. Based on these findings, a colocalization of different
      amines within the same neuron seems to be unlikely to occur in the cricket
      ventral nerve cord. With respect to the neuroanatomical description of amine
      containing neurons known physiological effects of biogenic amines and their
      possible neuromodulatory functions in insects are discussed.

PMID- 10084823
TI  - Biogenic amines in the brain of the honeybee: cellular distribution, development,
      and behavioral functions.
AB  - This review provides a summary of the cellular distribution of amine-containing
      neurons and the organization of aminergic pathways in the brain and
      suboesophageal ganglion of the honeybee. Neurons synthesizing the biogenic amines
      serotonin, dopamine, octopamine, and histamine are stained with well-defined
      polyclonal antisera. Since some of these aminergic neurons are uniquely
      identifiable, it is possible to follow their morphogenesis during brain
      development. Pharmacological studies show that aminergic mechanisms are involved
      in various behavioral modifications including associative learning. The
      immunocytochemical approach resolves at a single cell level the neural pathways
      that mediate adaptive behavioral changes.

PMID- 10084824
TI  - Distribution of dopamine receptors and dopamine receptor homologs in the brain of
      the honey bee, Apis mellifera L.
AB  - In the brain of the honey bee, Apis mellifera, the radioligands [3H]-SCH23390 and
      [3H]-spiperone recognise D1- and D2-like receptors, respectively. In addition to
      being pharmacologically distinct and exhibiting significantly different
      expression profiles during the lifetime of the bee, [3H]-SCH23390- and [3H]
      spiperone-binding sites differ markedly in their distribution within the brain.
      Estimates of [3H]-SCH23390-binding site density are highest in the somatal rind,
      whereas [3H]-spiperone-binding sites are most concentrated in the beta lobe
      neuropil of the mushroom bodies. Molecular cloning techniques have been used to
      identify two honey bee genes encoding dopamine receptor homologs. The first is
      the honey bee counterpart of a Drosophila D1-like dopamine receptor and is
      expressed in the mushroom bodies of both workers and drones. The second is
      related to D2-like dopamine receptors from vertebrates and is expressed in the
      brain of the bee, but the precise distribution of expression is not yet known.

PMID- 10084825
TI  - Stereological estimation of number and volume of pulmonary neuroepithelial bodies
      (NEBs) in neonatal hamster lungs.
AB  - The number and volume of pulmonary neuroepithelial bodies (NEBs) of 1- and 4-week
      old hamsters were estimated using unbiased stereological principles and
      systematic sampling techniques. For comparative purposes, volume estimations were
      also made in the carotid body, the parathyroid gland, and the adrenal medulla. A
      significant decrease was found in the total number of NEBs, immunoreactive for
      CGRP, between 1 and 4 weeks. Individual as well as cumulative NEB volume also
      decreased significantly. The cumulative NEB volume in 1-week-old hamsters was in
      the same range as the volumes of the carotids and parathyroids in the same
      animals. The postnatal decrease of the NEB number suggests that the NEBs are of
      primary potential importance in the neonatal stage, when they may complement the
      chemoreceptor function of the carotid bodies, which are relatively inactive at
      birth. Since the cumulative NEB volume (at least at the age of 1 week) is equal
      to that of the carotid bodies and the parathyroids, their physiological function
      may be of similar importance.

PMID- 10084826
TI  - Simple apparatus for plunge-freezing biological material: Some design
      considerations.

PMID- 10084827
TI  - Cellular distributions and functions of histamine, octopamine, and serotonin in
      the peripheral visual system, brain, and circumesophageal ring of the horseshoe
      crab Limulus polyphemus.
AB  - The data reviewed here show that histamine, octopamine, and serotonin are
      abundant in the visual system of the horseshoe crab Limulus polyphemus.
      Anatomical and biochemical evidence, including new biochemical data presented
      here, indicates that histamine is a neurotransmitter in primary retinal
      afferents, and that it may be involved in visual information processing within
      the lateral eye. The presence of histamine in neurons of the central nervous
      system outside of the visual centers suggests that this amine also has functions
      unrelated to vision. However, the physiological actions of histamine in the
      Limulus nervous system are not yet known. Octopamine is present in and released
      from the axons of neurons that transmit circadian information from the brain to
      the eyes, and octopamine mimics the actions of circadian input on many retinal
      functions. In addition, octopamine probably has major functions in other parts of
      the nervous system as octopamine immunoreactive processes are widely distributed
      in the central nervous system and in peripheral motor nerves. Indeed, octopamine
      modulates functions of the heart and exoskeletal muscles as well as the eyes. A
      surprising finding is that although octopamine is a circulating neurohormone in
      Limulus, there is no structural evidence for its release into the hemolymph from
      central sites. The distribution of serotonin in Limulus brain suggests this amine
      modulates the central processing of visual information. Serotonin modulates
      cholinergic synapses in the central nervous system, but nothing further is known
      about its physiological actions.

PMID- 10084828
TI  - Distribution of histamine in the CNS of different spiders.
AB  - Immunohistochemistry is used to demonstrate histamine-immunoreactivity in the CNS
      of spiders. We found histamine-immunoreactivity in the photoreceptors of
      different spiders. Therefore, we suggest that histamine is a neurotransmitter of
      photoreceptors in all arthropods, since it is also known to occur in the
      photoreceptors of the other main arthropod taxa (Merostomata, Crustacea, and
      Insecta). We also describe a system of only six omnisegmental histamine
      immunoreactive neurons within the central nervous system. These histamine
      immunoreactive neurons can be divided into two subgroups: a dorsal system with
      two cells per hemisphere and a ventral system with only one cell per hemisphere.
      All six cells have extended arborizations in both the motor and the sensory areas
      of all neuromeres in the suboesophageal ganglionic mass. In contrast to
      araneomorph spiders, two additional sets of histamine-immunoreactive neurons were
      detected in mygalomorph spiders. The first set consists of seventeen cells with
      their cell bodies located in the cheliceral ganglion and projecting to central
      areas of the protocerebrum. The second set contains many if not all sensory
      projections from the tarsal organs on all eight legs and the pedipalps to the
      Blumenthal neuropil.

PMID- 10084829
TI  - The distribution of histamine and serotonin in the barnacle's nervous system.
AB  - The use of antisera directed against conjugates of histamine and serotonin has
      revealed the locations of neurons labeling for these transmitters in the nervous
      system of barnacles. Photoreceptors label for histamine but not serotonin and
      also satisfy a number of other criteria indicating that histamine is their
      neurotransmitter. Photoreceptors also take up radioactively labeled histamine but
      not serotonin. Within the barnacle's brain no somata are consistently found that
      label with antiserum against histamine, but one to three pairs of small cells,
      depending on species, label with antiserum against serotonin. The most impressive
      serotonin-like immunoreactivity in the brain, however, is in a pair of large
      fibers ascending through the circumesophageal connectives and ramifying
      extensively. Within the ventral ganglion, the only other ganglion in the
      barnacle, ten pairs of cells label with antiserum against histamine. These
      neurons are confined to the posterior portion of the ganglion but ramify
      extensively throughout the ganglion. Antiserum against serotonin labels about 15
      cell pairs, depending on species, located throughout the ganglion. The positions
      of the arbors of many of these cells suggest that these amines have a role in
      modulating either the motor pathways underlying feeding or the visual pathways
      responsible for the detection of shadows.

PMID- 10084830
TI  - In memoriam: Georg Springer, M.A., M.D., D.Sc. (Hon).

PMID- 10084831
TI  - Prenatal and perinatal and perinatal risk factors for early onset schizophrenia,
      affective psychosis, and reactive psychosis.

PMID- 10084832
TI  - Commentary: there must be limits to the medicalisation of human distress.

PMID- 10084833
TI  - Meta-analysis of diabetes care in general practice. Like was not compared with
      like.

PMID- 10084834
TI  - Evidence based patient information. Computers can be used to tailor information
      to patients.

PMID- 10084835
TI  - Evidence based patient information. Differing standards of literacy are better
      catered for with computers.

PMID- 10084836
TI  - Evidence based patient information. Local policies would be better than a
      national strategy.

PMID- 10084837
TI  - Diagnosing serious child abuse. All healthcare team members should be alert to
      indicators of child abuse.

PMID- 10084838
TI  - Vitamin B-6. Many found relief for disorders for which no effective treatment
      exists.

PMID- 10084839
TI  - Vitamin B-6. Government guidelines are not based on scientific evidence.

PMID- 10084840
TI  - Albumin controversy continues. Lack of efficacy shows that treatments de not
      work.

PMID- 10084841
TI  - Beyond conflict of interest. BMJ's editors should publish their own conflicts of
      interests regularly.

PMID- 10084842
TI  - Beyond conflict of interest. Sponsored drug trials show more-favourable outcomes.

PMID- 10084843
TI  - Beyond conflict of interest. Biomedical journals need a concerted response
      against influence of tobacco industry.

PMID- 10084844
TI  - Beyond conflict of interest. Non-financial conflicts of interest are more serious
      than financial conflicts.

PMID- 10084845
TI  - A tribute to Yoshio Masui.

PMID- 10084846
TI  - Yoshio Masui and cell cycle control, past, present and future.

PMID- 10084847
TI  - Behavior of cyclin B and cyclin B-dependent kinase during starfish oocyte meiosis
      reinitiation: evidence for non-identity with MPF.
AB  - We reconsider the notion of MPF initiation, which is generally viewed as the
      prerequisite production of a small cdc2-cyclin B kinase activity sufficient to
      trigger its own self-amplification. Using starfish oocytes as a tool, we show
      that H1 kinase activation is not explosive, but rather is a gradual process in
      both time and space. We show further that the production of even a large H1
      kinase activity, either in MPF-microinjected or in hormone-stimulated oocytes, is
      not sufficient to trigger MPF amplification.

PMID- 10084848
TI  - [Cardiac hypertrophy and coronary reserve in endurance athletes].
AB  - Impaired coronary reserve (CR) with angiographic coronary arteries has been
      demonstrated in patients with left ventricular hypertrophy (LVH) in response to
      valvular heart disease or hypertension. To determine if adaptive LVH induced by
      intensive training may alter myocardial blood flow (MBF) and CR, 8 highly trained
      endurance tri- athletes (29.6 +/- 4.0 yrs, with echographic LVH) were compared
      with 6 control subjects (33.0 +/- 7.9 yrs, with a normal echographic
      examination). Triathletes entered the study if they had a left ventricular mass
      >120 g/m2 at 2-D echocardiographic measurements (mean = 148.6 +/- 19.8 g/m2). MBF
      was assessed using positron emission tomography (PET) with H2O15. Subjects
      underwent an intravenous bolus of 17- 25 mCi of H2)15 at baseline and after
      intravenous infusion of 0.80 mg/kg of dipyridimole; H2O15 examination was
      followed by an F18-fluorodeoxyglucose (FDG) myocardial imaging. CR was determined
      as the ration of maximal to basal myocardial blood flow. In comparison with
      controls, triathletes with LVH showed normal MBF values (0.74 +/- 0.1 vs 0.8 +/-
      0.2 ml/ml/min, p = 0.2), but an increased CR (3.8 +/- 0.7 vs 6.1 +/-1.9, p <
      0.05). In contrast with other forms of LVH, CR is not altered in LVH due intense
      physical training. These results suggest that LVH due to intensive physical
      training is associated with an increase in coronary blood flow capacity.

PMID- 10084849
TI  - Proceedings of the 8th International Symposium on Antiphospholipid Antibodies.
      Sapporo, Japan, 6-9 October 1998.

PMID- 10084850
TI  - [The 51st Seminar of Kostlivy. The Slovak Surgical Society, the 1st Surgical
      Clinic of the Medical School Hospital and the Medical School of Comenius
      University in Bratislava. Work presented on 5 December 1997 in Bratislava].

PMID- 10084851
TI  - [Disorders of liver function in complicated surgical procedures].

PMID- 10084852
TI  - [Eventration after laparotomy].

PMID- 10084853
TI  - [Complications after esophageal resection and its reconstruction].

PMID- 10084854
TI  - [Complications of anastomoses in esophageal resection in the neck versus the
      thorax].

PMID- 10084855
TI  - [Life-threatening hemorrhage in the thoracic region].

PMID- 10084856
TI  - [Complications after pulmonary resection].
AB  - This retrospective study analyses the postoperative complications of the 587 lung
      resections performed at our department in the period of 1993--1996. Of 587
      resections 435 ones were performed for bronchogenic cancer. The mean age of the
      patient at the time of operation was 53.3 years ranging from 9 to 79. 30 patients
      were 70 years old and older. In that group there were 452 men and 135 women. The
      most frequent resection procedure was lobectomy (61.2%) followed by pneumonectomy
      (19.8%), wedge resection (11%), bilobectomy (6.1%) and segmentectomy (1.9%).
      Bronchoplastic procedures made up 6.5% of all procedures. 5 patients died within
      30 days of the surgery (mortality 0.85%). 3 of them had undergone pneumonectomy
      (mortality 2.6%) and 2 of them lobectomy and bilobectomy (mortality 0.5%).
      Postoperative complications occurred in 89 patients (15.2%). In this group the
      mortality was significantly higher for the patients after pneumonectomy. The
      morbidity was significantly higher for patients 70 years or older (23.3%). The
      morbidity after pneumonectomy (9.5%) was not higher than the morbidity after less
      extensive resections. We conclude, that low incidence of mortality and major
      morbidity reflects careful preoperative management, selection of appropriate
      surgical procedure and anesthestesia and postoperative care.

PMID- 10084857
TI  - [Surgical complications of tracheal intubation--tracheal rupture].
AB  - Authors present case report of 47-year-old woman with a rupture of trachea in its
      lower part after an intubation with a double-lumen tube without any problems.
      Tracheal lesion was discovered at the end of operation after an extirpation of
      mediastinal tumor and wedge resection of lung during the examination of
      hermeticity of lung mechanical suture. Rupture was cured by suture resorbable
      monofilamental material. Development after operation wasn't any different than a
      common lung resection. In the lecture authors discuss the possible causes of
      tracheal rupture, different kinds of therapy, and complications.

PMID- 10084858
TI  - [Carcinoma of the rectum--stapling--pitfalls and complications].

PMID- 10084859
TI  - [Complications in acute pancreatitis].
AB  - Acute pancreatitis is discussed from the point of view her complications. The
      survey of local, organ and system complication is demonstrated, and the Atlanta
      classification is recalled. The complications are demonstrated at the mild acute
      pancreatitis and also at the severe acute pancreatitis. The complications are
      demonstrated on the own group of patients (period 1995-1997). Severe respiratory
      failure came later, but the letality was high. The renale or hepatorenale failure
      came formerly and equally as DIC were combined with practically absolutely
      letality.

PMID- 10084860
TI  - [Local complications of severe necrotizing pancreatitis and its surgical
      treatment].

PMID- 10084861
TI  - [Aortoduodenal fistulae after vascular reconstructive surgery].

PMID- 10084862
TI  - [Injuries of the aorta and inferior vena cava in laparoscopy].

PMID- 10084863
TI  - [Reoperation after osteosynthesis of fractures of the upper femoral bone].

PMID- 10084864
TI  - [Treatment of splenic hemorrhage by intervention on the splenic artery].

PMID- 10084865
TI  - [An unusual septic state with multiorgan involvement].

PMID- 10084866
TI  - [Complications of splenectomy].
AB  - The authors describe the problematic of postsplenectomy complications. The main
      group of complications came in the group of haematological indication to
      splenectomy. The high risk of complications present the haematological
      malignancy. The most serious illness complications came only in this group.

PMID- 10084867
TI  - [Treatment of iatrogenic injuries of the biliary tract during laparoscopic
      cholecystectomy].

PMID- 10084868
TI  - [Complications of low rectal anastomoses after mechanical suturing].

PMID- 10084869
TI  - [The 50th anniversary of the St. Petersburg Scientific Society of Historians of
      Medicine].

PMID- 10084870
TI  - [Organization of training and curriculum at the Medical Department of the Moscow
      University after introduction of the Code of 1835. 2. Introduction of the General
      Code of the Imperial Russian Universities of 1835 at the Medical Department of
      the Moscow University].

PMID- 10084871
TI  - Elizabeth Blackwell.

PMID- 10084872
TI  - Synthesis and pharmacokinetics of a novel macromolecular prodrug of Tacrolimus
      (FK506), FK506-dextran conjugate.
AB  - A novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate,
      was developed and its physico-chemical, biological and pharmacokinetic
      characteristics were studied. The conjugate was estimated to contain 0.45% of
      FK506 and the coupling molar ratio was approximately 1:1 (dextran-FK-506).
      Adsorption experiments using ion exchangers indicated that FK506-dextran
      conjugate acted as a weakly negatively charged macromolecule. Low molecular
      weight radioactive compound(s), which was eluted in the same fractions as
      [(3)H]FK506, was released from [(3)H]FK506-dextran conjugate by chemical
      hydrolysis with a half-life of 150 h in phosphate buffer. In vitro
      immunosuppressive activity of the conjugate, as assessed by the rat lymphocyte
      stimulation test, was almost comparable to that of free FK506, suggesting that
      biologically active FK506 could be liberated from the conjugate. In vitro
      biodistribution studies demonstrated that conjugation with the dextran derivative
      dramatically changed the pharmacokinetic properties of FK506 after intravenous
      injection in rats. AUC of the FK506-dextran conjugate was almost 2000 times
      higher than that of free FK506 and organ uptake clearances of the conjugate were
      significantly smaller than those of the free drug. Thus, the present study has
      demonstrated that the FK506-dextran conjugate behaves as a prodrug of FK506 with
      an extended blood circulating time and can be expected to have an improved
      therapeutic potency.

PMID- 10084873
TI  - Proceedings of the 4th annual Margaret E Mahoney Symposium on the State of the
      Nation's Health.

PMID- 10084874
TI  - The Fourth Annual Margaret E. Mahoney Symposium on the State of the Nation's
      Health. Keynote address.

PMID- 10084875
TI  - Presentation of the 1998 Margaret E. Mahoney Award to Marian Wright Edelman.

PMID- 10084876
TI  - Summary and next steps in achieving universal access.

PMID- 10084877
TI  - Accessing Useful Information: Challenges in Health Policy and Public Health.
      Proceedings of a national forum. March 23, 1998.

PMID- 10084879
TI  - 39th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.
      Orlando, Florida, USA. March 24-27, 1999. Abstracts.

PMID- 10084878
TI  - Challenges to accessing useful information in health policy and public health: an
      introduction to a national forum held at the New York Academy of Medicine, March
      23, 1998.

PMID- 10084880
TI  - 1st International Symposium on the Molecular Pathology and Clinical Aspects of
      Inflamed Liver: Alcohol and Cytokines. Toronto, Ontario, Canada. June 7-9, 1998.
      Abstracts.

PMID- 10084881
TI  - [Recommendations for organizational and structural changes to safeguard a
      preclinical medical treatment system].

PMID- 10084882
TI  - Value of magnetic-resonance cholangiopancreatography (MRCP) after unsuccessful
      endoscopic-retrograde cholangiopancreatography (ERCP).

PMID- 10084883
TI  - Family history of colorectal adenomatous polyps and increased risk of colorectal
      cancer.

PMID- 10084884
TI  - Differences in diagnostic criteria for gastric carcinoma between Japanese and
      Western pathologists.

PMID- 10084885
TI  - Pediatric gastrointestinal endoscopy in Malaysia.

PMID- 10084886
TI  - On the origin of the olfactory receptor family: receptor genes of the jawless
      fish (Lampetra fluviatilis).
AB  - In vertebrates, recognition of odorous compounds is based on a large repertoire
      of receptor subtypes encoded by a multigene family. Towards an understanding of
      the phylogenetic origin of the vertebrate olfactory receptor family, attempts
      have been made to identify related receptor genes in the river lampreys (Lampetra
      fluviatilis), which are descendants of the earliest craniates and living
      representatives of the most ancient vertebrates. Employing molecular cloning
      approaches led to the discovery of four genes encoding heptahelical receptors,
      which share only a rather low overall sequence identity but several of the
      characteristic structural hallmarks with vertebrate olfactory receptors.
      Furthermore, in situ hybridization studies demonstrated that the identified genes
      are expressed in chemosensory cells of the singular lamprey olfactory organ.
      Molecular phylogenetic analysis confirmed a close relationship of the lamprey
      receptors to vertebrate olfactory receptors and in addition demonstrated that
      olfactory genes of the agnathostomes diverged from the gnathostome receptor genes
      before those split into class I and class II receptors. The data indicate that
      the lamprey receptors represent the most ancient family of the hitherto
      identified vertebrate olfactory receptors.

PMID- 10084887
TI  - Proceedings of a symposium on effects of medical interventions on suicidal
      behavior. Miami, Florida, USA, February 26-28, 1998.

PMID- 10084888
TI  - Plates are better than broth for recovery of fastidious organisms from some
      specimen material.

PMID- 10084889
TI  - Critical observations on computerized analysis of banding patterns with
      commercial software packages.

PMID- 10084890
TI  - Recovery of Kingella kingae from blood and synovial fluid of two pediatric
      patients by using the BacT/Alert system.

PMID- 10084891
TI  - Disc testing of meningococci.

PMID- 10084893
TI  - Proceedings of the 7th Taisho International Symposium on Gastroenterology.
      Lansdowne, Virginia, USA. May 10, 1997.

PMID- 10084892
TI  - Imidazoline Receptor Workshop. Melbourne, Australia, 10 September 1997.
      Proceedings.

PMID- 10084894
TI  - Commentary on McIntyre IM, King CV, Staikos V, Gall J, Drummer OH. A fatality
      involving moclobemide, sertraline and pimozide. J Forensic Sci 1997;42:951-53.

PMID- 10084895
TI  - The distinguished service award medal of the Society for Vascular Surgery:
      Richard Warren's legacy to vascular surgery.

PMID- 10084896
TI  - HIV vaccine trial in Africa.

PMID- 10084897
TI  - From endothelial dysfunction to cardiovascular disease. Proceedings of the 1st
      meeting of the International Science Faculty on Endothelial Function. Lucerne,
      Switzerland, March 3-4, 1998.

PMID- 10084898
TI  - Genealogies and weak purifying selection.
AB  - The assumption that selection alters the genealogical tree of a sample of alleles
      from a population relative to the neutral expectation underlies several "tests of
      neutrality." Two recent papers have studied the effect of purifying selection;
      their suggestive but incomplete results indicate that, in the single site case,
      the shape of a gene genealogy for a locus may differ only from the neutral
      expectation. We verify this finding for weak selection using the "ancestral
      selection graph." We consider a wider range of models, including both a four
      allele single-site model and an infinite-sites model. Our results confirm the
      previous claim for the symmetric-mutation single site model. We emphasize,
      however, that a neutral-seeming genealogy is consistent with detectable effects
      of selection on the distribution of allele frequences within the sample. With
      selection operating, the information about a sample cannot be reduced to the
      genealogy. As a result, a distinction needs to be made between the selected sites
      themselves, for which the genealogy offers insufficient information, and linked
      neutral variation. This distinction seems to have been overlooked in previous
      papers, yet it has significant implications for the interpretation of data on DNA
      sequence variation. In particular, it predicts that under purifying selection,
      the frequency spectrum of neutral mutations will not reflect the skew toward rare
      polymorphisms at replacement sites even if there is no recombination between
      them. We caution, however, that the effect of weak selection on the genealogy is
      specific to the model; a (more realistic) model of multiple linked sites could
      lead to a more distorted genealogy than is observed for a single site.

PMID- 10084899
TI  - Change in recommendation for meningococcal vaccine for travelers.

PMID- 10084900
TI  - Evaluation and management guidelines.

PMID- 10084901
TI  - Evaluation and management guidelines.

PMID- 10084902
TI  - Evaluation and management guidelines.

PMID- 10084903
TI  - Evaluation and management guidelines.

PMID- 10084904
TI  - Evaluation and management guidelines.

PMID- 10084905
TI  - Cow's milk and chronic constipation in children.

PMID- 10084906
TI  - Cow's milk and chronic constipation in children.

PMID- 10084907
TI  - Cow's milk and chronic constipation in children.

PMID- 10084908
TI  - Biliary sludge extruding into the duodenum.

PMID- 10084909
TI  - Aleukemic leukemia cutis in an adolescent boy.

PMID- 10084910
TI  - Clinical recovery from acute ischemic stroke after early reperfusion of the brain
      with intravenous thrombolysis.

PMID- 10084911
TI  - Risk factors for infant homicide.

PMID- 10084912
TI  - Risk factors for infant homicide.

PMID- 10084913
TI  - Risk factors for infant homicide.

PMID- 10084914
TI  - A moviemaker's malady.

PMID- 10084915
TI  - [Psoriasis treatment in family practice now closer in agreement with the
      guidelines of the Dutch Society of General Practitioners].

PMID- 10084916
TI  - Establishing an ergonomics program.

PMID- 10084917
TI  - Contemporary understanding of the elbow.

PMID- 10084918
TI  - Prenatal detection of a Wilms' tumor.

PMID- 10084919
TI  - The Macrophage in Human Pathology: Update on its Role in Induction of the Immune
      Response. Proceedings of the 1998 European Macrophage Conference. September 17
      19, 1998.

PMID- 10084920
TI  - Bioterror defense initiative injects shot of cash.

PMID- 10084921
TI  - Chlamydia protein linked to heart disease.

PMID- 10084922
TI  - Fruit fly odor receptors found.

PMID- 10084923
TI  - Kennewick man gets his day in the lab.

PMID- 10084924
TI  - Culture collections seek global help.

PMID- 10084925
TI  - Canadian budget. Health research gets fundamental overhaul.

PMID- 10084926
TI  - First food-borne pathogen sequenced.

PMID- 10084927
TI  - New clues to how proteins link up to run the cell.

PMID- 10084928
TI  - Behind the headlines of endostatin's ups and downs.

PMID- 10084929
TI  - Johns Hopkins plagiarism policies.

PMID- 10084930
TI  - Recovering Seveso.

PMID- 10084931
TI  - Communication goes multimodal.

PMID- 10084932
TI  - A gender gap in autoimmunity.

PMID- 10084933
TI  - Malaria Workshop. Tokyo, Japan, June 15-16, 1997. Abstracts.

PMID- 10084934
TI  - [Nephrotoxicity of pesticides].

PMID- 10084935
TI  - [Spontaneous ruptures of the kidney and retroperitoneal hematomas in hemorrhagic
      fever with renal syndrome].

PMID- 10084936
TI  - [The 100th anniversary of the Ia. R. Kovalenko All-Russian Research Institute of
      Experimental Veterinary Science].

PMID- 10084937
TI  - Recent activities in otorhinolaryngology. Commemoration of the retirement of
      Professor Yoshiaki Nakai from the Department of Otolaryngology, Osaka City
      University Medical School, Japan.

PMID- 10084938
TI  - Percutaneous overdrive pacing in the out-of-hospital treatment of torsades de
      pointes.

PMID- 10084939
TI  - Surviving the new workplace.

PMID- 10084940
TI  - [Long-chain fatty acids of Pasteurella multocida nad Pasteurella haemolytica].
AB  - The relative contents of long-chain fatty acids in P. multocida and P.
      haemolytica were investigated. A dependence on the composition of the broth was
      established. Accordingly, comparative quantitative studies on fatty acid contents
      have to be conducted using bacteria grown with the same lot of broth medium. As
      for P. multocida, there were significant differences between the serovars (C14 in
      TDHM and C16, delta 2C18 in BPL). These differences are, however, not significant
      to replace serotyping. Highly significant differences were also detected between
      P. multocida isolates from nasal swabs and pneumonic lungs (interims of C14,
      delta C16 on BPL and BRU). The largest differences were measured for strains
      grown on BRU, which is interpreted as an expression of virulence. Significant
      differences were found between biotypes A and T of P. haemolytica, namely for
      C14, C16 in TDHM, and C14, delta C16, C16, C18 in BPL medium.

PMID- 10084941
TI  - [In vitro studies of adhesion and invasion by Salmonella strains of bovine
      epithelial cells].
AB  - 24 Salmonella strains were divided into three groups according to the
      circumstances of isolation. The adhesion and invasion abilities of the strains
      were determined using two permanent cell lines (IEC-6, VERO) and an epithelial
      cell line from the small intestine of a calf fetus (pKD). Strains of different
      groups showed no differences in their ability to adhere to the cells tested.
      Significant differences were found for the invasion ability. Strains isolated
      from organs of calves suffering from salmonellosis showed a significant higher
      invasiveness for permanent cell lines and a considerable higher invasiveness for
      pKD cells than strains of the other groups.

PMID- 10084942
TI  - [Efficacy of maternal Salmonella antibodies and experimental oral infection of
      chicks with Salmonella enteritidis].
AB  - Distribution of maternally transmitted Salmonella antibodies and their protective
      effects were studied in the progeny of broiler breeder birds which had been
      vaccinated with live S. Typhimurium and inactivated S. Enteritidis vaccines.
      Vaccination resulted in a significant increase of the antibody concentration in
      yolk of hatching eggs and in serum and jejunum of the progeny of immunized
      breeder birds. Higher antibody titres for isotypes IgG and IgA were still seen on
      day 21 of age. Antibody production of isotypes IgA and IgM by the chickens
      themselves was found between 14 and 21 days of age. Two challenge models (10(2)
      cfu/bird on day 1 of age and a seeder bird model, respectively) were used to
      evaluate the efficacy of maternal antibodies against challenge with S.
      Enteritidis. Using both models numbers of challenge organisms were lower in the
      caeca of the progeny of immunized parent birds between day 7 and day 21 of age
      (maximum about 1.5 log10 units) compared with control chicks. The results
      indicate the efficacy of maternally transferred antibodies but it remains the
      question of their practical relevance. The effects of acquired maternal
      antibodies on an active immunization of the progeny of immunized breeder birds
      with live Salmonella vaccines are discussed.

PMID- 10084943
TI  - [Experimental affecting of pulmonary clearance of Pasteurella multocida induced
      pneumonia in swine].
AB  - The pulmonary clearance of Pasteurella multocida in weaner pigs was not affected
      by Carrageenan and Silica, two substances which block the function of
      monocytes/macrophages. Neutropenia, caused by the application of hydroxyurea,
      however, inhibit the pulmonary clearance markedly and reduced the severity of
      simultaneously induced pneumonias considerably. This indicates the importance of
      polymorphonuclear neutrophils for early clearance mechanisms and their
      inflammation inducing and maintaining effects.

PMID- 10084944
TI  - [LPS receptor expression and lps binding capacity of monocytes and macrophages in
      swine].
AB  - The expression of the lipopolysaccharide (LPS) receptor CD14, being of importance
      for an effective immune response, and the direct measurable binding of LPS
      molecules by alveolar macrophages (AM), peritoneal macrophages (PM) and
      peripheral blood mononuclear cells (PBMC) of swine were determined. Additionally,
      the influence of an experimental intrabronchial infection with Pasteurella
      multocida on these parameters was investigated. Whereas the AM and the PM
      differed only negligibly regarding their share of CD14 bearing and LPS binding
      cells, in contrast to AM the intensity of the LPS-binding of PM was significantly
      higher. Among the PBMC, two populations could be detected which expressed the
      CD14 with different intensity, whereas the LPS-binding of both populations was
      similarly pronounced. Following infection of the animals, AM showed an unchanged
      percentage of CD14 positive cells and simultaneously an increased CD14 receptor
      expression. On the other hand, the percentage of the LPS-binding cells rose,
      while no changes of the intensity of LPS-binding were observable. The studies
      revealed that intrabronchial infection results in local and systemic alterations
      of CD14 expression and LPS-binding capacity of different cell populations.
      However, a direct correlation between the appearance of CD14- and LPS-binding
      does not seem to inevitably exist, indicating probably CD14-independent LPS
      binding.

PMID- 10084945
TI  - [Investigation of outer membrane proteins of Pasteurella. 2: Iron-regulated outer
      membrane proteins of Pasteurella multocida and Pasteurella haemolytica].
AB  - Pasteurella multocida and Pasteurella haemolytica produce specific proteins in
      the outer membrane under iron-depleted conditions. Pasteurella multocida serovar
      A expresses these proteins of molecular masses of 76 and 96 kDa as determined by
      electrophoresis. The analogous serovar D produces a further iron-regulated
      protein of 85 kDa. The Pasteurella haemolytica strains of serovar A1, A6 and T
      contain iron-regulated outer membrane proteins of molecular masses of 71, 77 and
      100 kDa. These proteins possess binding positions for iron ions. Both Pasteurella
      multocida and Pasteurella haemolytica strains utilize iron from porcine and
      bovine transferrin, but not from haemin and haemoglobin.

PMID- 10084946
TI  - [Significance of motility of Salmonella enteritidis and Salmonella typhimurium as
      a virulence factor and on the expression of the inhibition phenomenon in vitro
      and in vivo in SPF chickens].
AB  - Methods of immunoprophylaxis for poultry using live Salmonella vaccines are
      increasingly gaining in importance. Methods of a simple and reliable
      bacteriological as well as serological differentiation between vaccine and field
      strains will be of decisive importance for the acceptance and use of live
      Salmonella vaccines. The absence of motility in Salmonella strains may be a
      marker fulfilling these criteria. The studies described served to examine whether
      virulence and the ability to inhibit other Salmonella strains could be influenced
      by the absence of motility in Salmonella (S.) Enteritidis and (S.) Typhimurium.
      In a cell-culture model (IEC 6) under in vitro conditions, non-motile transposon
      mutants (TnphoA) of S. Enteritidis and S. Typhimurium exhibited a clearly reduced
      invasion potential in comparison with the respective motile parental strain.
      Under in vitro conditions (nutrient broth culture), the inhibitory potential of
      these non-motile mutants was also reduced compared to the motile original
      strains. In contrast, in vivo studies in a-few-days-old chickens revealed that
      there was no reduction of the virulence of non-motile mutants of S. Enteritidis
      and S. Typhimurium in comparison with the motile parental strain. In day-old
      chicks, the inhibitory potential of non-motile strains was significantly reduced
      and in some cases, had even become completely lost.

PMID- 10084947
TI  - [Use of a fast test to detect rotavirus in feces].
AB  - The commercially available immunoassay "OnSite Rotavirus" was used for the
      detection of animal rotaviruses in 113 faecal samples. The sensitivity of the
      test was 88% and the specificity 96% compared with reference methods (EIA, EM).
      This test would detect approximately 4.4 x 10(6) to 1.8 x 10(7) virus particles
      per ml. The presence of virus could be demonstrated in fresh faecal samples from
      cattle, horses and pigs within a few minutes. The rotaviruses of group A were
      identified independently of the virus serotype. Further results and additional
      problems of using this test kit are described.

PMID- 10084948
TI  - Oxytocin-induced Ca2+ responses in human myometrial cells.
AB  - Complex spatiotemporal changes in intracellular Ca2+ were monitored in an
      immortalized human myometrial cell line (PHM1-41) and first-passage human
      myometrial cells after oxytocin stimulation (1. 0-1000 nM). Laser cytometry
      revealed intracellular Ca2+ oscillations in both culture systems starting at 1.0
      nM, which were followed by repetitive Ca2+ transients by 10-15 min that lasted
      for at least 90 min. The amplitude of the initial Ca2+ spike was dose dependent,
      while the frequency of Ca2+ oscillations identified by Fast Fourier Transform
      (FFT) tended to increase with dose. Removal of oxytocin resulted in termination
      of oscillations. Analysis of the sources of the Ca2+ involved in oscillations
      indicated that the major contribution to oscillation frequencies of </= 6 mHz in
      cells was from the inositol 1,4,5-trisphosphate-sensitive pool, accounting for
      about 60% of the frequencies. Most of the remaining frequencies were attributable
      to extracellular Ca2+, which presumably comes from plasma membrane channels other
      than L-type channels. When oscillation frequencies exceeded 6 mHz, a significant
      contribution from a ryanodine-sensitive Ca2+ pool was detected. Eight-bromo-cAMP
      suppressed both the initial Ca2+ spike and the long-term oscillations.
      Prostaglandin E1 and E2 caused a significant increase in the frequency of
      oxytocin-induced Ca2+ oscillations. FFT analysis may be of considerable value for
      study of the mechanisms of rhythmic Ca2+ transients and their function in
      myometrial cells, as well as the mechanisms by which uterotonins and tocolytic
      agents impact myometrial Ca2+ regulation.

PMID- 10084949
TI  - A monoclonal antibody against chorion proteins of the sea bass Dicentrarchus
      labrax (Linnaeus, 1758): studies of chorion precursors and applicability in
      immunoassays.
AB  - The monoclonal antibody DLE7 was obtained against 44- to 50-kDa polypeptides
      solubilized from the vitelline envelope of the Mediterranean sea bass
      Dicentrarchus labrax. In Western blot analysis of chorion lysates it recognized
      cross-reactive bands at 44 kDa, 48 kDa, and 110 kDa. Previous affinity blotting
      with concanavalin-A showed that most of solubilized bands were glycosylated.
      Enzymatic deglycosylation of chorion proteins followed by Western blot analysis
      with DLE7 showed that the 48-kDa and 110-kDa antigens were differentially
      affected by endoglycosidase-F treatment. When DLE7 was employed in
      immunofluorescence analysis, isolated chorions and ovarian cryosections stained
      intensely. Positivity was also observed in liver cryosections of spawning females
      but not in liver of males and nonspawning females. To study the origin and
      delivery of chorion proteins, DLE7 was used in Western blot analysis of liver
      homogenates and blood serum of spawning females. Cross-reacting bands were
      detected in liver (90 kDa) and serum (180 kDa, 50 kDa). DLE7 was also used for
      the first time to set up an indirect ELISA assay to detect egg antigens in the
      blood of egg-producing females, raising the possibility of using DLE7 as a female
      specific marker of spawning for sea bass.

PMID- 10084950
TI  - Gestational regulation of granulocyte-colony stimulating factor receptor
      expression in the human placenta.
AB  - A number of cytokines and their receptors are abundantly expressed at the materno
      fetal interface and are thought to have a function in the regulation of
      placentation. Granulocyte-colony stimulating factor (G-CSF) is expressed by
      stromal cells in both placental tissue and maternal decidua throughout
      placentation. In this study, we examined the expression of placental G-CSF
      receptor (G-CSFR) mRNA and protein throughout gestation by ribonuclease
      protection assays, Western blotting, and immunohistochemistry. The major
      placental form of G-CSFR mRNA, corresponding to a membrane-bound form of the
      protein, was present in first-trimester placental tissues; levels decreased in
      second- and were highest in third-trimester placental tissues. Two placental G
      CSFR molecules, 120 kDa and 150 kDa, were detected in first- and third-, but not
      second-, trimester tissues. The level of the 150-kDa G-CSFR was greater in the
      third- than in first-trimester samples. These differences were irrespective of
      whether or not the patients had received prostaglandin E1 analogues,
      prostaglandin E1 analogues and oxytocin, oxytocin alone, or mifepristone before
      labor. We demonstrated by immunohistochemistry that interstitial cytotrophoblast
      in first- and second-trimester decidual tissue and cytotrophoblast in term fetal
      membranes express G-CSFR. These data demonstrate that the expression of specific
      forms of placental G-CSFR is strictly cell type- and developmental stage
      specific, and they suggest that G-CSFR may be important in decidual invasion of
      cytotrophoblast and in trophoblast function during placentation.

PMID- 10084951
TI  - Fas and Fas ligand messenger ribonucleic acid and protein expression in the rat
      corpus luteum during apoptosis-mediated luteolysis.
AB  - Apoptosis has been found to occur during regression of the corpus luteum (CL) in
      many species. The Fas (APO-1/CD95) receptor, a transmembrane protein that induces
      apoptosis in the cell when bound to Fas ligand (FasL), may be involved. This
      study established and quantitated the presence and regulation of Fas receptor and
      FasL in the rat CL during pregnancy and postpartum. Using immunohistochemistry,
      FasL was localized in CL during pregnancy and postpartum. Fas was localized at
      Day 1 of pregnancy and at the time of luteolysis. Both Fas and FasL mRNA were
      found to be expressed throughout pregnancy and postpartum using reverse
      transcription-polymerase chain reaction (RT-PCR). Relative quantitative RT-PCR
      established that expression of FasL mRNA increased significantly at Day 22 of
      pregnancy and decreased by Day 3 postpartum. Spontaneous apoptosis of rat CL
      placed in an in vitro culture model with serum-free medium was examined by
      analysis of extracted DNA using 3' end-labeling. Treatment with an anti-rat Fas
      monoclonal antibody demonstrated a reduction in the occurrence of spontaneous
      apoptosis. These data support a role for Fas receptor and FasL in rat CL
      apoptosis during luteolysis.

PMID- 10084952
TI  - The negative effect of repeated equine chorionic gonadotropin treatment on
      subsequent fertility in Alpine goats is due to a humoral immune response
      involving the major histocompatibility complex.
AB  - In dairy goats, the use of eCG as a convenient hormone for the induction of
      ovulation is necessary for out-of-season breeding and artificial insemination.
      However, repeated eCG treatments are followed by decreased fertility in goats
      inseminated at a fixed time after treatment. In this report, we show the presence
      of anti-eCG antibodies in plasma of treated goats. A 500 IU eCG injection induces
      a humoral response, with variable concentrations of anti-eCG antibody being
      produced in individual goats. The analysis of successive anti-eCG immune
      responses over several years has demonstrated the existence of different
      populations of goats, defined as low, medium, and high responders. By the use of
      two caprine microsatellites located inside (OLADRB) and outside (BM1258) the
      major histocompatibility complex (MHC), a significant association (p < 0.05)
      between the anti-eCG antibody response and some MHC-DRB alleles was found. Goats
      with high antibody concentrations at the time of eCG injection (> 2.5 microg/ml)
      exhibited a much lower kidding rate than did other females (41.3% vs. 66.7%).
      Lower fertility of these goats, inseminated at a fixed time after eCG treatment,
      might be due to the observed delay in estrus occurrence and the preovulatory LH
      surge.

PMID- 10084953
TI  - Effect of labor induction on the expression of oxytocin receptor, cytochrome P450
      aromatase, and estradiol receptor in the reproductive tract of the late-pregnant
      ewe.
AB  - In this study, we investigated the timing of changes in aromatase, estradiol
      receptor, and oxytocin receptor expression in ovine uterine and placental tissues
      before parturition. Labor was induced by betamethasone injection into the fetus
      on Days 130-132 of pregnancy. Tissue samples were collected at injection and then
      every 14 h until labor (56 h) from four ewes at each time point. Samples were
      analyzed for aromatase, estradiol receptor, and oxytocin receptor expression by
      in situ hybridization; for oxytocin binding to its receptor using a specific
      antagonist; and for estradiol receptor quantitation by immunocytochemistry.
      Aromatase mRNA expression increased by 14 h postinjection (p < 0.02) in the fetal
      villi and remained high until labor. Expression of estradiol and oxytocin
      receptor mRNAs was unchanged in myometrium but increased in the endometrial
      luminal epithelium by 28 h (p < 0.05) and remained high until labor. Estradiol
      receptor protein concentration increased modestly at labor while oxytocin
      receptor binding in the luminal epithelium changed in parallel to the mRNA
      concentration. IN CONCLUSION: 1) induction of aromatase may facilitate the
      expression of endometrial estradiol and oxytocin receptors in the placentome, 2)
      changes in endometrial rather than myometrial oxytocin receptor may be important
      in inducing parturition, and 3) the transcription of estradiol receptor and
      oxytocin receptor in the uterine epithelium are positively correlated during
      parturition.

PMID- 10084954
TI  - Development of nuclear transfer and parthenogenetic rabbit embryos activated with
      inositol 1,4,5-trisphosphate.
AB  - The present study was carried out to evaluate the effects of different activation
      protocols, enucleation methods, and culture media on the development of
      parthenogenetic and nuclear transfer (NT) rabbit embryos. Electroporation of 25
      mM inositol 1,4, 5-trisphosphate (IP3) in calcium- and magnesium-free PBS
      immediately induced a single intracellular calcium transient in 6 out of 14
      metaphase II-stage rabbit oocytes evaluated during a 10-min recording period. The
      percentage of oocytes treated with IP3 followed by 6-dimethylaminopurine (IP3 +
      DMAP) that cleaved (83.9%) and reached the blastocyst stage (50%) was
      significantly higher (p < 0.05) than those activated with multiple pulses (61.6%
      and 30.1%, respectively) or treated with ionomycin + DMAP (52.9% and 5.7%,
      respectively). Development of IP3 + DMAP-activated rabbit oocytes and in vivo
      fertilized zygotes in different culture media was studied. Development of
      activated oocytes to the blastocyst stage in Earle's balanced salt solution
      (EBSS) supplemented with MEM nonessential amino acids, basal medium Eagle amino
      acids, 1 mM L-glutamine, 0.4 mM sodium pyruvate, and 10% fetal bovine serum (FBS)
      (EBSS-complete) (40.6%) was significantly higher (p < 0.05) than those that
      developed in either Dulbecco's Modified Eagle's medium (DMEM)/RPMI + 10% FBS
      (15.5%) or CR1aa + 10% FBS (4%) medium. In addition, 100% of in vivo-fertilized
      rabbit zygotes developed to the blastocyst stage in EBSS-complete. A third set of
      experiments was carried out to study the efficiency of blind versus stained
      (Hoechst 33342) enucleation of oocytes. Twenty-nine of 48 blind enucleated and
      IP3 + DMAP-activated oocytes cleaved (60.4%), and 15 (31.2%) subsequently reached
      the blastocyst stage, whereas 9 of 52 oocytes enucleated using epifluorescence
      (17.3%) cleaved, and none of these reached the blastocyst stage. When the above
      parameters that yielded the highest blastocysts were combined in an NT experiment
      using adult rabbit fibroblast nuclei, 72.2% (39 of 54) of the fused nuclear
      transplant embryos cleaved and 29.6% (16 of 54) reached the blastocyst stage.

PMID- 10084955
TI  - Development of cytotrophoblast columns from explanted first-trimester human
      placental villi: role of fibronectin and integrin alpha5beta1.
AB  - Human first-trimester floating mesenchymal villi explanted onto gels of collagen
      I or Matrigel were observed to undergo de novo development of anchoring sites.
      These consisted of cytotrophoblast columns that formed by proliferation of stem
      villous cytotrophoblast cells, as revealed by whole-mount and thin-section
      microscopy and incorporation of bromodeoxyuridine into DNA. Column formation
      occurred exclusively at the distal tips of the villi. No column formation was
      observed in tissue explanted onto agarose. On Matrigel, the developing columns
      penetrated downwards into the matrix, whereas on collagen I, cytotrophoblast
      sheets spread across the surface of the gel and merged to form a shell. The
      developing columnar cytotrophoblast up-regulated integrins alpha1beta1 and
      alpha5beta1 and produced an extracellular matrix containing oncofetal
      fibronectin, as in vivo. Function-blocking antibodies were used to investigate
      the role of the integrin-fibronectin interaction in anchoring villus development
      on collagen I. Antibodies to fibronectin and the integrin subunits alpha5 and
      beta1, added at 24 h, all changed the pattern of cytotrophoblast outgrowth. Anti
      fibronectin caused cell rounding within the cytotrophoblast sheet and increased
      the population of single cells at its periphery. Anti-integrin alpha5 caused
      rounding and redistribution of cells within the outgrowth. In the presence of
      anti-integrin beta1, cell-collagen interactions within the sheet were
      destabilized, often leading to the appearance of an annulus of aggregated cells
      at the periphery. These results show that 1) mesenchymal villi retain the
      potential to form anchoring sites until at least the end of the first trimester,
      2) adhesion to a permissive extracellular matrix stimulates cytotrophoblast
      proliferation and differentiation along the extravillous lineage, 3) integrin
      alpha5beta1-fibronectin interactions contribute significantly to anchorage of the
      placenta to uterine extracellular matrix. We suggest that as the developing
      placenta ramifies, new sites of anchorage form whenever peripheral villi contact
      decidua. This process is predicted to contribute to the stability of the
      placental-decidual interface.

PMID- 10084956
TI  - Stage-specific excitation of cannabinoid receptor exhibits differential effects
      on mouse embryonic development.
AB  - Anandamide (N-arachidonoylethanolamine), an arachidonic acid derivative, is an
      endogenous ligand for both the brain-type (CB1-R) and spleen-type (CB2-R)
      cannabinoid receptors. We have previously demonstrated that preimplantation mouse
      embryos express mRNA for these receptors and that the periimplantation uterus
      contains the highest level of anandamide yet discovered in a mammalian tissue. We
      further demonstrated that 2-cell mouse embryos exposed to low levels of
      anandamide (7 nM) or other known cannabinoid agonists in culture exhibit markedly
      compromised embryonic development to blastocysts and that this effect is mediated
      by CB1-R. In contrast, the present study demonstrates that blastocysts exposed in
      culture to the same low levels of cannabinoid agonists exhibited accelerated
      trophoblast differentiation with respect to fibronectin-binding activity and
      trophoblast outgrowth. Again, these effects resulted from activation of embryonic
      CB1-R. There was a differential concentration-dependent effect of cannabinoids on
      the trophoblast, with an observed inhibition of differentiation at higher doses.
      These results provide evidence for the first time that cannabinoid effects are
      differentially executed depending on the embryonic stage and cannabinoid levels
      in the environment. Since uterine anandamide levels are lowest at the sites of
      implantation and highest at the interimplantation sites, the new findings imply
      that site-specific levels of anandamide and/or other endogenous ligands in the
      uterus may regulate implantation spatially by promoting trophoblast
      differentiation at the sites of blastocyst implantation.

PMID- 10084957
TI  - Comparative expression of luteinizing hormone and follicle-stimulating hormone
      receptors in ovarian follicles from high and low prolific sheep breeds.
AB  - Expression of gonadotropin receptors and granulosa cell sensitivity to
      gonadotropin hormones by small (1-3 mm) and large (3.5-7 mm) follicles were
      compared in Romanov (ROM, ovulation rate = 3) and Ile-de-France (IF, ovulation
      rate = 1) ewes in the early and late follicular phase. In healthy follicles, LH
      receptor levels in granulosa cells increased with increasing follicular size (p <
      0. 001) while FSH receptor levels decreased (p < 0.05). In granulosa cells of
      large follicles, LH receptor (LHR) mRNA levels were greater in the late than in
      the early follicular phase (p < 0.001, p < 0.05, for ROM and IF, respectively).
      In the early follicular phase, LHR levels in granulosa (p < 0.001) and theca
      cells (p < 0.05) of small follicles were greater in ROM than in IF ewes. FSH
      receptor mRNA levels in granulosa cells of small and large ROM follicles were
      greater than in the corresponding IF follicles (p < 0.05). Finally, a greater
      responsiveness (increase in cAMP secretion) to both FSH and hCG was observed by
      granulosa cells collected during the early follicular phase from ROM vs. IF ewes.
      Data provide evidence that the greater ovulation rate in the ROM as compared to
      the IF breed is associated with a greater gonadotropin responsiveness during the
      early follicular phase.

PMID- 10084958
TI  - Opposing changes in 3alpha-hydroxysteroid dehydrogenase oxidative and reductive
      activities in rat leydig cells during pubertal development.
AB  - The enzyme 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) has an important role
      in androgen metabolism, catalyzing the interconversion of dihydrotestosterone
      (DHT) and 5alpha-androstane-3alpha,17beta-diol (3alpha-DIOL). The net direction
      of this interconversion will affect the amount of biologically active ligand
      available for androgen receptor binding. We hypothesize that in Leydig cells,
      differential expression of 3alpha-HSD enzymes favoring one of the two directions
      is a mechanism by which DHT levels are controlled. In order to characterize
      3alpha-HSD in rat Leydig cells, the following properties were analyzed: rates of
      oxidation (3alpha-DIOL to DHT) and reduction (DHT to 3alpha-DIOL) and preference
      for the cofactors NADP(H) and NAD(H) (i.e., the oxidized and reduced forms of
      both pyridine nucleotides) in Leydig cells isolated on Days 21, 35, and 90
      postpartum. Levels of 3alpha-HSD protein were measured by immunoblotting using an
      antibody directed against the liver type of the enzyme. Levels of 3alpha-HSD
      protein and rates of reduction were highest on Day 21 and lowest on Day 90. The
      opposite was true for the rate of 3alpha-HSD oxidation, which was barely
      detectable on Day 21 and highest on Day 90 (59.08 +/- 6.35 pmol/min per 10(6)
      cells, mean +/- SE). Therefore, the level of 3alpha-HSD protein detectable by
      liver enzyme was consistent with reduction but not with oxidation. There was a
      clear partitioning of NADP(H)-dependent activity into the cytosolic fraction of
      Leydig cells, whereas on Days 35 and 90, Leydig cells also contained a microsomal
      NAD(H)-activated 3alpha-HSD. We conclude that 1) the cytosolic 3alpha-HSD in
      Leydig cells on Day 21 behaves as a unidirectional NADPH-dependent reductase; 2)
      by Day 35, a microsomal NAD(H)-dependent enzyme activity is present and may
      account for predominance of 3alpha-HSD oxidation over reduction and the resultant
      high capacity of Leydig cells on Day 90 to synthesize DHT from 3alpha-DIOL.

PMID- 10084959
TI  - Expression of the erythropoietin receptor by trophoblast cellsin the human
      placenta.
AB  - Nonclassical sites of erythropoietin (EPO) and erythropoietin receptor (EPO-R)
      expression have been described that suggest new physiological roles for this
      hormone unrelated to erythropoiesis. The recent finding of EPO expression by
      trophoblast cells in the human placenta prompted us to consider whether these
      cells also express EPO-R. With use of immunocytochemistry, EPO-R was identified
      in villous and extravillous cytotrophoblast cells, as well as in the
      syncytiotrophoblast at all gestational ages. EPO-R was also expressed by cells
      within the villous core, including endothelial cells of fetoplacental blood
      vessels. Placental tissues and isolated and immunopurified trophoblast cells, as
      well as trophoblast-derived choriocarcinoma Jar cells, expressed immunoreactive
      EPO-R on Western blot. EPO-R mRNA was also detected in the same placental tissues
      and trophoblast cells by nested-primer reverse transcription-polymerase chain
      reaction. Finally, EPO-R was functional insofar as the receptor was
      phosphorylated on tyrosine residues in response to exogenous EPO treatment of
      cultured trophoblast or Jar cells. Thus, the present findings support the
      hypothesis that trophoblast cells of the human placenta express EPO-R. In view of
      these results, taken together with previous work demonstrating EPO expression by
      the same cells, an autocrine role for this hormone in the survival,
      proliferation, or differentiation of placental trophoblast cells is proposed.

PMID- 10084960
TI  - Phenotypic analysis and proliferative responses of human endometrial granulated
      lymphocytes during the menstrual cycle.
AB  - The in vivo function of the unusual population of CD56+ CD16- endometrial
      granulated lymphocytes (eGLs) in human endometrium is unknown; their increased
      numbers in the secretory phase of the menstrual cycle suggests that they may play
      a role in the immunobiology of nonpregnant endometrium. In the present study, the
      phenotype and proliferative responses of eGLs at various phases of the menstrual
      cycle were compared with those in early pregnancy. Endometrial GLs were highly
      purified (> 98% CD56+) using immunomagnetic separation, and the expression of
      cell surface antigens was examined in smears using a double immunohistochemical
      labeling technique. Proliferative responses to mitogens and interleukin 2 (IL-2)
      were assessed in hanging drops in 60-well Terasaki plates. There was low to no
      expression of CD3, CD8, CD16, HML-1, L-selectin, and CD25 (IL-2 receptor alpha)
      on CD56+ cells isolated from nonpregnant and pregnant endometrium. The expression
      of CD2, CD49a, and CD122 (IL-2 receptor beta, IL-2Rbeta), however, increased from
      the proliferative to the late secretory phase of the menstrual cycle. In
      contrast, CD11a, CD69, and CD49d expression was high and did not vary with
      menstrual cycle phase; CD49d levels were significantly reduced in early
      pregnancy. Unlike early-pregnancy eGLs, none of the CD56+ eGL cultures throughout
      the menstrual cycle displayed phytohaemagglutinin (PHA)-induced
      lymphoproliferation. In contrast, eGLs from nonpregnant endometrium in the
      presence of 5 or 100 U/ml IL-2 after 48- and 120-h incubation showed significant
      proliferative responses, as did eGL cultures from early pregnancy. A
      significantly reduced number of proliferative phase eGL cultures proliferated in
      response to IL-2 compared to secretory phase and early-pregnancy eGL cultures.
      The IL-2-induced proliferative responses of CD56+ eGLs were associated with
      increased IL-2Rbeta (CD122) expression. These findings demonstrate 1)
      differential eGL expression of CD2, CD49a, and CD122 during the menstrual cycle;
      2) differential IL-2-induced eGL proliferative responses during the menstrual
      cycle; and 3) differences between eGLs from nonpregnant and pregnant endometrium
      in CD49d expression and their ability to respond to PHA.

PMID- 10084961
TI  - Sperm-oviduct interaction: induction of capacitation and preferential binding of
      uncapacitated spermatozoa to oviductal epithelial cells in porcine species.
AB  - After mating, inseminated spermatozoa are transported to the oviduct. They attach
      to and interact with oviductal epithelial cells (OEC). To investigate sperm-OEC
      interactions, we used chlortetracycline to study the capacitation status of boar
      spermatozoa in coculture with homologous OEC and cells of nonreproductive origin
      (LLC-PK1, porcine kidney epithelial cell line). Boar spermatozoa were cocultured
      with OEC and LLC-PK1 cells for 15, 60, 120, or 240 min. The proportion of
      capacitated spermatozoa in coculture with the isthmic and ampullar cells
      increased significantly (p < 0.05) during incubation. However, most spermatozoa
      in coculture with LLC-PK1 cells or blank (medium only) remained uncapacitated. In
      addition, preferential binding of uncapacitated, capacitated, or acrosome-reacted
      boar spermatozoa to OEC and the other cell type was investigated. Our approach
      was to vary the proportions of uncapacitated, capacitated, or acrosome-reacted
      boar spermatozoa in suspension using long preincubation and
      lysophosphatidylcholine treatment of semen prior to a very short incubation with
      OEC or LLC-PK1 cells. The results showed that the majority of spermatozoa that
      were bound to OEC or LLC-PK1 cells were uncapacitated and that a significant
      relationship existed between the relative proportion of uncapacitated spermatozoa
      in the control samples and those bound to LLC-PK1 cells (r2 = 0.43, p < 0.005).
      However, there was no correlation between the proportion of uncapacitated
      spermatozoa in the control samples and the proportion of those bound to isthmic
      or ampullar cells. In conclusion, the results clearly demonstrated the specific
      nature of the sperm-OEC interaction in the porcine species. This interaction is
      initiated by uncapacitated spermatozoa binding to OEC and is continued by the
      induction of capacitation in cocultured spermatozoa.

PMID- 10084962
TI  - Signal transduction and biological function of placenta growth factor in primary
      human trophoblast.
AB  - Placenta growth factor (PlGF), a member of the vascular endothelial growth factor
      family of angiogenic factors, is prominently expressed by trophoblast. In
      addition to its role as a paracrine angiogenic factor within the placenta and
      endometrium, presence of its receptor, Flt-1, on trophoblast suggests that PlGF
      also may have an autocrine role(s) in regulating trophoblast function. To
      elucidate its role in trophoblast, we examined the signal transduction and
      functional responses of primary human trophoblast to PlGF. Exogenous PlGF induced
      specific activation of the stress-activated protein kinase (SAPK) pathways, c-Jun
      N terminal kinase (JNK) and p38 kinase, in primary term trophoblast with little
      to no induction of the extracellular signal regulated kinase (ERK-1 and -2)
      pathways. In contrast, PlGF induced significant ERK-1 and -2 activity in human
      umbilical vein endothelial cells but did not induce JNK or p38 activity. PlGF
      induced activation of the SAPK signaling pathways protected trophoblast from
      growth factor withdrawal-induced apoptosis, but it did not protect trophoblast
      from apoptosis induced by the pro-inflammatory cytokines, interferon gamma and
      tumor necrosis factor alpha. These results provide the first direct evidence of a
      biochemical and functional role for PlGF/Flt-1 in normal trophoblast and suggest
      that aberrant PlGF expression during pregnancy may impact upon trophoblast
      function as well as vascularity within the placental bed.

PMID- 10084963
TI  - Spatiotemporal expression of cyclooxygenase 1 and cyclooxygenase 2 during delayed
      implantation and the periimplantation period in the Western spotted skunk.
AB  - Embryonic development in the western spotted skunk is arrested after blastocyst
      formation for about 200 days. This developmental arrest is believed to be due to
      insufficiency of uterine conditions to support continuous development.
      Implantation and decidualization are defective in cyclooxygenase 2 (Cox2)-, but
      not Cox1-, deficient mice. We therefore used Northern and in situ hybridization
      to investigate changes in uterine expression of Cox1 and Cox2 genes during
      various stages of pregnancy in the spotted skunk. Cox1 was constitutively
      expressed at all stages of pregnancy examined, but it did exhibit localized up
      regulation in the trophoblast and necks of uterine glands at early implantation
      sites. Cox2 expression was highly regulated with little or no expression during
      delayed implantation. Cox2 expression was first detected in the uterus and
      trophoblast prior to blastocyst attachment and remained detectable for 5-6 days
      after blastocyst attachment. Cox2 expression was also localized in the luminal
      and glandular epithelia of uterine segments located between implantation
      chambers. Changes in Cox expression were not correlated with the abrupt increase
      in uterine weight that occurs simultaneously with renewed embryonic development
      but was correlated with an influx of serum proteins into the uterus observed in a
      previous study.

PMID- 10084964
TI  - A contraceptive peptide vaccine targeting sulfated glycoprotein ZP2 of the mouse
      zona pellucida.
AB  - In this study, we have mapped and characterized a B cell epitope of sulfated
      glycoprotein ZP2 (ZP2) as a step toward the development of a multi-epitope zona
      pellucida (ZP) vaccine. Recombinant polypeptides expressed by random
      deoxyribonuclease-digested fragments of ZP2 cDNA were screened for binding to IE
      3, a monoclonal antibody to murine ZP2. Positive clones contained cDNA inserts
      encoding polypeptide corresponding to ZP2(103-134). When normal or ovariectomized
      female mice were immunized with three overlapping peptides that span this region
      of ZP2 (101-120, 111-130, 121-140), only ZP2(121-140) elicited IgG antibodies
      that reacted with mouse ovarian ZP, indicative of the presence of native B
      epitope and helper T cell epitope in ZP2(121-140). To more finely map the ZP2 B
      cell epitope, a random peptide display library was screened with the IE-3
      antibody, and a consensus tetramer sequence VxYK that matched the ZP2(123-126)
      sequence VRYK was located. Competitive immunofluorescence analysis with single
      alanine-substituted VxYK peptides ranked the relative contribution of the three
      critical B cell epitope residues as Y > V > K. A chimeric peptide was constructed
      that contained the YRYK motif of ZP2 and a bovine RNase T cell epitope. Although
      (C57BL/6xA/J) F1 (B6AF1) female mice immunized with the chimeric peptide
      developed ZP antibody response, this peptide elicited antibody only in mice of
      the histocompatibility complex (MHC) H-2(k or b) haplotype. In contrast, ZP2(121
      140) peptide elicited antibody in inbred mice with three additional mouse MHC
      haplotypes. Moreover, although ZP2(121-140) contained a T cell epitope, no
      oophoritis was observed after immunization of B6AF1 mice with ZP2(121-140) in
      complete Freund's adjuvant (CFA). In a preliminary trial, female B6AF1 mice
      immunized with ZP2(121-140) in CFA had reduced litter sizes as compared with mice
      injected with CFA alone.

PMID- 10084965
TI  - Sperm migration into and through the oviduct following artificial insemination at
      different stages of the estrous cycle in the rat.
AB  - In order to examine whether sperm migration into and through the oviduct follows
      an invariable pattern or is subject to regulation, rats in proestrus, estrus,
      metestrus, or diestrus were inseminated in the upper third of each uterine horn
      with 10-20 million epididymal spermatozoa. Three or eight hours later, the
      numbers of spermatozoa free and adhering to the epithelium in the ampullary and
      isthmic segments were determined. A significantly higher number of spermatozoa
      were recovered in estrus than in other stages, at 3 h than at 8 h, and at all
      stages from the isthmus than from the ampulla. Spermatozoa adhering to the
      epithelium were observed only in proestrus and estrus and in the isthmus. The
      effect of exogenous estradiol-17beta (E2) and progesterone (P4) on sperm
      migration was investigated in rats in which the estrous cycle was inhibited
      pharmacologically. E2 facilitated sperm migration into the oviduct and P4
      antagonized this effect, whereas P4 alone had no effect. Concomitant treatment
      with E2+P4 induced adhesion of spermatozoa to the oviductal epithelium. In
      conclusion, the pattern of sperm migration into and through the rat oviduct
      varies with the stage of the cycle, being dependent on E2 and P4. The adhesion of
      spermatozoa to the rat oviductal epithelium is stage- and segment-specific and
      requires the combined action of both hormones.

PMID- 10084966
TI  - A quantitative study of changes in the human corpus luteum microvasculature
      during the menstrual cycle.
AB  - Endothelial cells are the most abundant cell type in the corpus luteum (CL), and
      changes in blood vessels have been proposed to play a pivotal role in CL
      regression. We have studied quantitatively the changes in the human granulosa
      luteal microvasculature in CL of various ages: young (Days 17-19 of the cycle),
      mature (Days 20-24), old (Days 25-27), early regressing (follicular phase of the
      following cycle), and late regressing (luteal phase of the following cycle).
      Blood vessels were identified by immunohistochemical staining for the endothelial
      cell marker CD34. Because of the anisotropy of blood vessels, both vertical and
      transverse sections of the granulosa-lutein layer (GLL) were used to estimate
      relative (volume, surface, and length densities) and absolute (mean cross
      sectional area) vascular variables. Full luteinization from young to mature CL
      was accompanied by a 61% increase in the mean cross-sectional area of vascular
      profiles and a 52% increase in the mean volume of granulosa-lutein cells, as an
      estimator of changes in the volume of the GLL. In old and early regressing CL,
      there was a progressive increase in relative structural vascular variables, due
      to the shrinkage of the GLL, whereas the mean cross-sectional area of capillaries
      showed a 53% decrease from mature to old CL. Finally, in late regressing CL,
      there was a decrease in most relative structural variables, in spite of the
      increasingly shrunken GLL. The decrease in the capillary diameter found at the
      late luteal phase most likely leads to a decreased blood flow, and early changes
      in blood vessels could initiate and/or accelerate CL regression.

PMID- 10084967
TI  - Localization of ubiquitin and ubiquitin cross-reactive protein in human and
      baboon endometrium and decidua during the menstrual cycle and early pregnancy.
AB  - We have examined the distribution of ubiquitin and the related ubiquitin cross
      reactive protein (UCRP) in paraffin-embedded sections of human and baboon
      endometrium and decidua by immunoperoxidase or immunofluorescence cytochemistry
      with antibodies raised against ubiquitin, UCRP, CD45, and insulin-like growth
      factor-binding protein-1. Anti-ubiquitin immunoreactivity was present in the
      nonpregnant endometrium, particularly in the glandular epithelial cells, and up
      regulated in endometrial stromal cells as they decidualized at the beginning of
      pregnancy. Anti-UCRP immunoreactivity was absent from nonpregnant tissue but
      accumulated to high levels in decidual cells during pregnancy. Western blotting
      indicated that immunoreactivity was primarily due to the presence of ubiquitin
      and UCRP conjugated to other proteins, and that although levels of ubiquitin
      protein conjugates do not change substantially during pregnancy, decidualization
      is accompanied by the appearance of conjugates of UCRP. Baboon uterine tissues
      demonstrated a similar distribution of the two proteins, which indicates that the
      baboon may be a useful model for study of the role of the ubiquitin system and
      UCRP in the establishment of pregnancy in humans.

PMID- 10084968
TI  - Effects of glucocorticoids on maturation of pig oocytes and their subsequent
      fertilizing capacity in vitro.
AB  - The aim of this study was to assess the possible role of glucocorticoids in the
      maturation of pig oocytes and their subsequent fertilizing capacity in vitro. Pig
      cumulus-enclosed oocytes collected from prepubertal gilts were cultured in
      Waymouth MB752/1 medium supplemented with sodium pyruvate (50 microg/ml), LH (0.5
      microg/ml), FSH (0.5 microg/ml), and estradiol-17beta (1 microg/ml) in the
      presence or absence of cortisol or dexamethasone (DEX) for 24 h; they then were
      cultured without hormonal supplements in the presence or absence of cortisol or
      DEX for an additional 16-24 h. Treatment of cumulus-enclosed or denuded oocytes
      with increasing concentrations of cortisol or DEX for 48 h resulted in a dose
      response inhibition of germinal vesicle breakdown (GVB). Increasing duration (12
      48 h) of treatment with DEX (10 microg/ml) led to a time-dependent inhibition of
      GVB, which achieved statistical significance by 12 h. The addition of DEX (10
      microg/ml) to maturation medium immediately after culture or at 12 h, 24 h, or 36
      h after culture also decreased the percentage of oocytes with GVB. When oocytes
      were exposed to DEX for 48 h, the maturation rate was reduced. The degree of this
      reduction was dependent on DEX, and a concentration of DEX higher than 0.1
      microg/ml was needed. The inhibitory effect of DEX on the maturation of oocytes
      was prevented by the glucocorticoid receptor antagonist RU-486. Exposure of
      oocytes to DEX for 40 h did not prevent sperm penetration, affect the incidence
      of polyspermy, or decrease the ability of oocytes to form a male pronucleus. The
      intracellular concentration of glutathione (GSH) in cumulus-enclosed oocytes was
      4.4 mM per oocyte. Exposure of oocytes to DEX (0.01-10 microg/ml) had no effect
      on GSH concentration. These results demonstrate that glucocorticoids directly
      inhibit the meiotic but not cytoplasmic maturation of pig oocytes in vitro. This
      inhibitory effect is not mediated through a decrease in the level of
      intracellular GSH.

PMID- 10084969
TI  - A 105- to 94-kilodalton protein in the epididymal fluids of domestic mammals is
      angiotensin I-converting enzyme (ACE); evidence that sperm are the source of this
      ACE.
AB  - SDS-PAGE analysis of luminal fluid from the ram testis and epididymis revealed a
      protein of about 105 kDa in the fluid in the caput epididymal region. The
      molecular mass of this fluid protein shifted from 105 kDa to 94 kDa in the distal
      caput epididymidis and remained at 94 kDa in the lower regions of the epididymis.
      The possible sperm origin of this protein was suggested by the decrease in
      intensity of a 105-kDa compound on the sperm plasma membrane extract and by its
      total disappearance from the fluid of animals with impaired sperm production
      caused by scrotal heating. The 94-kDa protein was purified from ram cauda
      epididymal fluid, and a rabbit polyclonal antiserum was obtained. This antiserum
      showed that membranes of testicular sperm and sperm from the initial caput were
      positive for the presence of an immunologically related antigen. The protein was
      immunolocalized mainly on the flagellar intermediate piece, whereas in some
      corpus and caudal sperm, only the apical ridge of the acrosomal vesicle was
      labeled. The purified protein was microsequenced: its N-terminal was not found in
      the sequence database, but its tryptic fragments matched the sequence of the
      angiotensin I-converting enzyme (ACE). Indeed, the purified 94-kDa protein
      exhibited a carboxypeptidase activity inhibited by specific blockers of ACE. All
      the soluble seminal plasma ACE activity in the ram was attributable to the 94-kDa
      epididymal fluid ACE. The polyclonal antiserum also showed that a soluble form of
      ACE appeared specifically in the caput epididymal fluid of the boar, stallion,
      and bull. This soluble form was responsible for all the ACE activity observed in
      the fluid from the distal caput to the cauda epididymidis in these species. Our
      results strongly suggest that the epididymal fluid ACE derives from the germinal
      form of ACE that is liberated from the testicular sperm in a specific epididymal
      area.

PMID- 10084970
TI  - Glucocorticoid receptor-mediated post-ceramide inhibition of the interleukin
      1beta-dependent induction of ovarian prostaglandin endoperoxide synthase-2 in
      rats.
AB  - Ovulation may constitute a cyclic, inflammatory-like process, wherein interleukin
      (IL)-1 induction and increased biosynthesis of prostanoids may feature
      prominently. In excess, glucocorticoids, potent anti-inflammatory agents, may
      exert an antiovulatory effect. This paper addresses the possibility that the
      antiovulatory action of glucocorticoids may be partly due to interference with
      ovarian prostanoid biosynthesis. Specifically, we examined the effect of
      treatment with dexamethasone, a synthetic glucocorticoid, on the IL-1-induced
      expression and activity of ovarian prostaglandin endoperoxide synthase (PGS)-2,
      the inducible variety of the rate-limiting enzyme in the prostaglandin cascade.
      Treatment of cultured whole ovarian dispersates from immature rats with
      dexamethasone for 48 h produced a significant decrease (98.9% inhibition) in the
      IL-1-supported expression of PGS-2 transcripts. Comparably marked inhibition was
      also noted for the corresponding immunoreactive protein. The dexamethasone effect
      was not limited to the IL-1-mediated induction of PGS-2 transcripts, comparable
      suppression being noted for the IL-1-mediated up-regulation of ovarian
      transcripts corresponding to IL-1beta, the IL-1 receptor antagonist, and the type
      I IL-1 receptor. The order of potency of the glucocorticoids studied was
      dexamethasone > prednisolone = cortisol. Dexamethasone proved equally effective
      in suppressing the induction of PGS-2 transcripts by congeners of the
      sphingomyelin-ceramide cycle (e.g., C-2 ceramide, sphingomyelinase, and
      sphingosine). The dexamethasone effect proved glucocorticoid-specific, as
      synthetic agonists representative of the progestin (R-5020), androgen (R-1881),
      and estrogen (diethylstilbestrol) steroid series proved to be without effect.
      Cotreatment with RU-486 resulted in reversal of the ability of dexamethasone to
      suppress PGS-2 activity or expression. Taken together, these observations suggest
      that dexamethasone is capable of glucocorticoid receptor-mediated/post-ceramide
      suppression of IL-1-supported ovarian PGS-2 transcript, protein, and activity.
      These findings are compatible with the view that the chronic anovulatory state
      associated with adrenal hyperactivity or glucocorticoid excess may be due in part
      to inhibition of ovarian prostaglandin biosynthesis.

PMID- 10084971
TI  - Effect of pelvic endometrial implants on overall reproductive functions of female
      rats.
AB  - The effects of pelvic endometrial implants on the overall reproductive potential
      of female rats were investigated. After homologous transplantation in the
      peritoneum, the ectopic endometrium developed into highly vascularized nodes that
      gradually increased in mass until the 9th week postsurgery and then plateaued. In
      the presence of these implants, overall reproductive function was adversely
      affected. The effect was of greatest magnitude during 50-70 days
      posttransplantation. As compared with values in corresponding controls, ovulation
      was reduced by 43% (6 of 14) (p < 0.05), mating rate was reduced by 44% (12 of
      27) (p < 0.025), and premature termination of pregnancy occurred in 34% (5 of 15)
      of rats. Wastage of pregnancy, which included complete termination or reduction
      of fetal number, occurred during the postimplantation course of gestation.
      Furthermore, 100% of the rats with transplants failed to respond to the
      copulomimetic stimulation for the induction of pseudopregnancy (p < 0.01,
      compared with corresponding controls). However, on exposure to vasectomized
      males, 46% (6 of 13) of these rats exhibited development of pseudopregnancy (p <
      0.05, compared with corresponding group receiving copulomimetic stimulation).
      Increased rate of mating failure and differential pseudopregnancy rates after
      copulomimetic and natural cervical stimulation suggest that the rats with
      endometrial explants possibly had an absence or a short appearance of behavioral
      estrus. Hormonal assessment during the preovulatory phase showed a tendency
      toward lower mean levels of preovulatory estradiol and significantly lower LH (p
      < 0.01) and progesterone (p < 0.01) concentrations. The adversely affected
      reproductive functions may be a secondary consequence of these altered endocrine
      milieus.

PMID- 10084972
TI  - Ovarian hormone secretory response to gonadotropins and nitric oxide following
      chronic nitric oxide deficiency in the rat.
AB  - Ovarian hormone secretion is regulated by gonadotropins, and it has been
      demonstrated that this response is modulated by nitric oxide (NO). The focus of
      this study was to determine the effect of chronic NO deficiency on the secretion
      of ovarian steroids. Female rats were given N-nitro-L-arginine (L-NNA; 0.6 g/L)
      in their drinking water, and vaginal smears were obtained daily. By 4 wk of
      treatment, all the rats were in constant estrus or proestrus. At 6-8 wk the
      animals were killed; the ovaries were removed and incubated in the presence of
      eCG (1 IU/ml) and hCG (1 IU/ml) and/or S-nitroso-L-acetyl penicillamine (an NO
      donor, S-NAP; 0.1 mM) for 4 h. Medium was collected at 30-min intervals, and
      estradiol, progesterone, and androstenedione were measured. Ovaries from
      proestrous rats served as controls. Ovaries from L-NNA-treated animals had a
      greater basal and gonadotropin-stimulated release of estradiol but not of
      androstenedione or progesterone in comparison to ovaries from untreated controls.
      S-NAP decreased the gonadotropin-stimulated estradiol, progesterone, and
      androstenedione in ovaries from NO-deficient rats. Steroid secretion in controls
      was not responsive to S-NAP. We conclude that chronic NO inhibition produces
      constant estrus due to increased estradiol production and that NO acts to inhibit
      estradiol and androstenedione production.

PMID- 10084973
TI  - Volume-regulated anion and organic osmolyte channels in mouse zygotes.
AB  - Whole-cell currents in mouse zygotes were measured using the patch-clamp
      technique in whole-cell mode. Upon exposure to hypotonic medium, patch-clamped
      zygotes increased in volume and developed a large swelling-activated current. The
      swelling-activated current was blocked by Cl- channel blockers, and the magnitude
      of the current and reversal potential were dependent on the Cl- gradient. Thus,
      the swelling-activated current had the properties of a current mediated by anion
      channels. However, in addition to being permeable to Cl- and I- (with I- having
      the greater permeability), there was also a significant swelling-activated
      conductance to aspartate and taurine, indicating that the swelling-activated
      channels in zygotes conduct not only inorganic anions but organic osmolytes as
      well. This swelling-activated anion and organic osmolyte pathway likely underlies
      the ability of zygotes to recover from an increase in volume, and it may function
      to regulate intracellular amino acid concentrations.

PMID- 10084974
TI  - Characterization of glycolysis and pentose phosphate pathway activity during
      sperm entry into the mouse oocyte.
AB  - Studying the events that occur during gamete fusion and sperm decondensation in
      the oocyte remains difficult because sperm-oocyte fusion and subsequent sperm
      decondensation represent a short part of the fertilization process, and their
      exact timing is difficult to determine. There is therefore a need for greater
      understanding of the events that occur during this period. The main purpose of
      this study was to examine the metabolic aspects of this time frame by
      characterizing glucose metabolism (glycolytic and pentose phosphate pathway [PPP]
      activities) during sperm fusion and decondensation into zona-free oocytes in
      mice. The metabolism of glucose through both glycolysis and the PPP was measured
      in ovulated MII oocytes, free of cumulus cells, and the levels of glucose
      metabolized were found to be low. Upon sperm entry, both glycolytic and PPP
      activity increased substantially. To determine whether this elevation in glucose
      metabolism was part of the activation process, the metabolism of
      parthenogenetically activated oocytes was measured, and no increase in metabolism
      was observed. The characterization of glucose metabolism during sperm fusion and
      decondensation into the oocyte, and comparison to parthenogenetically activated
      oocytes, showed that the fertilizing sperm is responsible for an increase in both
      glycolytic and PPP activity during fusion and/or decondensation. The significance
      of this observation during the fertilization process and for the developing
      embryo is as yet unclear and warrants further investigation.

PMID- 10084975
TI  - Modulation of calcium mobilization in aortic rings of pregnant rats: Contribution
      of extracellular calcium and of voltage-operated calcium channels.
AB  - Pregnancy is associated with decreased vascular responsiveness to vasopressor
      stimuli. We have tested the involvement of Ca2+ mobilization in myotropic
      responses of aortic rings obtained from pregnant and virgin rats. Contractions of
      the rings to phenylephrine, in the absence of calcium in the bathing medium, were
      lower in tissues from virgin than from pregnant rats. Concentration-response
      curves to CaCl2 that were measured after stimulation by phenylephrine in the
      absence of Ca2+ were shifted to higher levels of contraction. This was not
      observed when KCl was used to prestimulate the aorta. D-600, a phenylalkylamine
      calcium channel blocker, similarly inhibited these responses to CaCl2 in tissues
      from both pregnant and virgin animals. D-600 exerted a concentration-dependent
      inhibition of responses to phenylephrine and KCl. However, the calcium antagonist
      was less effective in aortic rings of pregnant than of virgin rats. Basal 45Ca2+
      uptake was lower in aortic rings from pregnant than from virgin rats, and Bay K
      8644 was unable to reverse this difference. The time course of basal and
      stimulated (KCl) 45Ca2+ influx was lower in aorta of pregnant rats at all times
      studied. Moreover, when the intracellular calcium pools were emptied with
      phenylephrine, the refilling of these pools was delayed in aortic rings of
      pregnant rats. These results indicate an altered extracellular calcium
      mobilization of aortic rings from pregnant rats. These changes may be due to a
      functional alteration of the voltage-operated calcium channels during pregnancy.

PMID- 10084976
TI  - Oviductin, the Xenopus laevis oviductal protease that processes egg envelope
      glycoprotein gp43, increases sperm binding to envelopes, and is translated as
      part of an unusual mosaic protein composed of two protease and several CUB
      domains.
AB  - The glycoprotein envelope surrounding the Xenopus laevis egg is converted from an
      unfertilizable to a fertilizable form during transit through the pars recta
      portion of the oviduct. Envelope conversion involves the pars recta protease
      oviductin, which selectively hydrolyzes envelope glycoprotein gp43 to gp41.
      Oviductin cDNA was cloned, and sequence analysis revealed that the protease is
      translated as the N terminus of an unusual mosaic protein. In addition to the
      oviductin protease domain, a protease domain with low identity to oviductin was
      present, possessing an apparent nonfunctional catalytic site. Three CUB domains
      were also present, which are related to the mammalian spermadhesin molecules
      implicated in mediating sperm-envelope interactions. We propose that during post
      translational proteolytic processing of the mosaic oviductin glycoprotein, the
      processed N-terminal protease domain is released coupled to two C-terminal CUB
      domains and constitutes the enzymatically active protease molecule. In functional
      studies, isolated coelomic egg envelopes treated with oviductin purified from the
      oviduct showed a dramatic increase in sperm binding. This observation established
      that oviductin alone was the oviductal factor responsible for converting the egg
      envelope to a sperm-penetrable form, via an increase in sperm binding. Trypsin
      mimicked oviductin's effect on envelope hydrolysis and sperm binding,
      demonstrating that gp43 processing is the only requirement for envelope
      conversion.

PMID- 10084977
TI  - Production of cloned calves following nuclear transfer with cultured adult mural
      granulosa cells.
AB  - Adult somatic cell nuclear transfer was used to determine the totipotent
      potential of cultured mural granulosa cells, obtained from a Friesian dairy cow
      of high genetic merit. Nuclei were exposed to oocyte cytoplasm for prolonged
      periods by electrically fusing quiescent cultured cells to enucleated metaphase
      II cytoplasts 4-6 h before activation (fusion before activation [FBA] treatment).
      Additionally, some first-generation morulae were recloned by fusing blastomeres
      to S-phase cytoplasts. A significantly higher proportion of fused embryos
      developed in vitro to grade 1-2 blastocysts on Day 7 with FBA (27.5 +/- 2.5%)
      than with recloning (13.0 +/- 3.6%; p < 0. 05). After the transfer of 100
      blastocysts from the FBA treatment, survival rates on Days 60, 100, 180, and term
      were 45%, 21%, 17%, and 10%, respectively. Ten heifer calves were delivered by
      elective cesarean section; all have survived. After the transfer of 16 recloned
      blastocysts, embryo survival on Day 60 was 38%; however, no fetuses survived to
      Day 100. DNA analyses confirmed that the calves are all genetically identical to
      the donor cow. It is suggested that the losses throughout gestation may in part
      be due to placental dysfunction at specific stages. The next advance in this
      technology will be to introduce specific genetic modifications of biomedical or
      agricultural interest.

PMID- 10084978
TI  - Tissue plasminogen activator and its receptor in the human amnion, chorion, and
      decidua at preterm and term.
AB  - The plasminogen activator system consists of two proteins: tissue plasminogen
      activator (tPA) and urokinase plasminogen activator (uPA), which act upon their
      specific receptors to generate plasmin from plasminogen located on the cell
      surface. Plasmin then acts directly and indirectly to degrade the components of
      the extracellular matrix (ECM). This process is likely to be important in the
      normal turnover of the ECM of fetal membranes and in its premature weakening in
      preterm premature rupture of the fetal membranes. Quantitative Northern analysis
      and in situ hybridization have shown that the decidua expresses mRNA for tPA.
      However, the immunolocalized tPA protein was most strongly associated with the
      amnion and chorion, as was its receptor annexin II, suggesting that the amnion
      and chorion are the targets for decidual tPA. At term, decidual tPA expression
      was unaffected by labor, and the tPA receptor was elevated both before and after
      labor. At preterm, the converse was found: decidual tPA expression was
      significantly (p < 0. 05) up-regulated by labor, but the tPA receptor was not.
      The results suggest that the generation of plasmin at term would be controlled by
      an increased concentration of the tPA receptor in the amnion and chorion, whereas
      at preterm a pathological increase in plasmin would be generated by an
      overexpression of tPA, initiated by labor.

PMID- 10084979
TI  - Flow cytometric cell cycle analysis of cultured porcine fetal fibroblast cells.
AB  - Normal development of nuclear transfer embryos is thought to be dependent on
      transferral of nuclei in G0 or G1 phases of the cell cycle. Therefore, we
      investigated the cell cycle characteristics of porcine fetal fibroblast cells
      cultured under a variety of cell cycle-arresting treatments. This was achieved by
      using flow cytometry to simultaneously measure cellular DNA and protein content,
      enabling the calculation of percentages of cells in G0, G1, S, and G2+M phases of
      the cell cycle. Cultures that were serum starved for 5 days contained higher (p <
      0.05) percentages of G0+G1 (87.5 +/- 0. 7) and G0 cells alone (48.3 +/- 9.7)
      compared with rapidly cycling cultures (G0+G1: 74.1 +/- 3.0; G0: 2.8 +/- 1.2).
      Growth to confluency increased (p < 0.05) G0+G1 percentages (85.1 +/- 2.8) but
      did not increase G0 percentages (6.0 +/- 5.3) compared to those in cycling
      cultures. Separate assessment of small-, medium-, and large-sized cells showed
      that as the cell size decreased from large to small, percentages of cells in
      G0+G1 and G0 alone increased (p < 0.05). We found 95.2 +/- 0.3% and 72.2 +/-
      12.0% of small serum-starved cells in G0+G1 and G0 alone, respectively. Cultures
      were also treated with cell cycle inhibitors. Treatment with dimethyl sulfoxide
      (1%) or colchicine (0.5 microM) increased percentages of cells in G0 (24.8 +/-
      20.0) or G2+M (37.4 +/- 4.6), respectively. However, cells were only slightly
      responsive to mimosine treatment. A more complete understanding of the cell cycle
      of donor cells should lead to improvements in the efficiency of nuclear transfer
      procedures.

PMID- 10084980
TI  - Morphologic evaluation and actin filament distribution in porcine embryos
      produced in vitro and in vivo.
AB  - Porcine embryos produced in vitro have a small number of cells and low viability.
      The present study was conducted to examine the morphological characteristics and
      the relationship between actin filament organization and morphology of porcine
      embryos produced in vitro and in vivo. In vitro-derived embryos were produced by
      in vitro maturation, in vitro fertilization (IVF), and in vitro development. In
      vivo-derived embryos were collected from inseminated gilts on Days 2-6 after
      estrus. In experiment 1, in vitro-derived embryos (</= 8-cell stage) collected 12
      48 h after IVF were separately fixed, stained by orcein, and examined under phase
      contrast microscopy. It was found that 27% of 2-cell, 74% of 3-cell, 51% of 4
      cell, and 74% of 5- to 8-cell-stage embryos were abnormal in morphology.
      Morphological anomalies included fragmentation (no nucleus in one or more than
      one blastomere) and/or binucleation (two nuclei in one or more than one
      blastomere). In experiment 2, actin filament distribution of the embryos at 2
      cell to blastocyst stages that were produced in vivo and in vitro were stained by
      rhodamine-phalloidin and examined by confocal microscopy. Actin filaments were
      distributed in all in vivo-derived embryos at the cell cortex, and at the joints
      of cells and perinucleus in 2- to 8-cell-stage embryos and in some cells of
      morulae and blastocysts. Actin filaments were also distributed in the cortex and
      at the joints of cells of all in vitro-produced embryos. However, only 20% of in
      vitro-produced embryos at 2- to 8-cell stages had perinuclear actin filaments in
      all blastomeres. Most in vitro-produced embryos had fewer perinuclear actin
      filaments or did not have perinuclear actin filaments in some blastomeres.
      Fragmentation and binucleate blastomeres were not observed in in vivo-derived
      embryos. In vivo-derived Day 5 (136.5 +/- 60.4 nuclei per blastocyst) and Day 6
      (164.5 +/- 51.9 nuclei per blastocyst) blastocysts had significantly (p < 0.001)
      more cells than in vitro-produced Day 6 blastocysts (37. 3 +/- 11.7 nuclei per
      blastocyst). In experiment 3, when cytochalasin D, an inhibitor of microfilament
      polymerization, was included in the culture medium, it prevented 2- to 4-cell
      stage embryos from developing to the blastocyst stage. These results indicate
      that abnormal actin filament distribution is one possible reason for abnormal
      embryo cleavage and small cell numbers in pig embryos produced in vitro. Culture
      conditions that mediate normal actin filament distribution may result in an
      improvement in embryo quality.

PMID- 10084981
TI  - Identification of progesterone-dependent messenger ribonucleic acid regulatory
      patterns in the rhesus monkey endometrium by differential-display reverse
      transcription-polymerase chain reaction.
AB  - We used differential-display reverse transcription-polymerase chain reaction
      (DDRT-PCR) to identify different patterns of progesterone (P4)-dependent gene
      regulation in rhesus monkey endometria. Complementary DNA populations
      representing the proliferative phase (estrogen dominant, EcDNA) and an inadequate
      secretory phase (low level of P4, IcDNA) were compared with a cDNA population
      representing an adequate secretory phase (normal level of P4, PcDNA). We were
      able to distinguish four different levels of mRNA regulation: 1) up-regulation by
      P4 during an adequate secretory phase, 2) autologous down-regulation (IcDNA
      versus PcDNA), 3) lower abundance in IcDNA compared to PcDNA, and 4) P4-dependent
      inhibition of EcDNA gene expression. We isolated and sequenced 16 fragments
      representing these different levels of P4 regulation. The sequence of three
      fragments that were autologously down-regulated (I1, I2, I4) matched previously
      entered GenBank mRNAs: I1 encodes serine/threonine protein phosphatase A; I2
      encodes oxobutanoate dehydrogenase E1b-beta; and I4 encodes line-1 reverse
      transcriptase homologue. Six other fragments exhibited homology to
      uncharacterized expressed sequence tags, sequence site tags, and cosmid clones.
      The remaining seven fragments exhibited no significant homology to GenBank
      entries at this time. The various patterns of P4-dependent gene regulation
      identified in the present study are likely to play roles in the temporal
      orchestration of events that lead to proper maturation of the endometrium.

PMID- 10084982
TI  - Spermatid translocation in the rat seminiferous epithelium: coupling membrane
      trafficking machinery to a junction plaque.
AB  - In this study, we demonstrate that specialized junction plaques that occur
      between Sertoli cells and spermatids in the rat testis support microtubule
      translocation in vitro. During spermatogenesis, Sertoli cells are attached to
      spermatids by specialized adhesion junctions termed ectoplasmic specializations
      (ESs). These structures consist of regions of the plasma membrane adherent to the
      spermatid head, a submembrane layer of tightly packed actin filaments, and an
      attached cistern of endoplasmic reticulum. It has been proposed that motor
      proteins on the endoplasmic reticulum interact with adjacent microtubules to
      translocate the junction plaques, and hence the attached spermatids, within the
      epithelium. If this hypothesis is true, then isolated junctions should support
      microtubule transport. To verify this prediction, we have mechanically isolated
      rat spermatids, together with their attached ESs, and tested them for their
      ability to transport microtubules in vitro. Most assays were done in the presence
      of 2 mg/ml testicular cytosol and at room temperature. ESs attached to spermatids
      supported microtubule translocation. In some cases in which motility events were
      detected, microtubules moved smoothly over the junction site. In others, the
      movement was slow but progressive, saltatory and "inch-worm-like." No motility
      was detected in the absence of exogenous ATP or in the presence of apyrase (an
      enzyme that catalyses the breakdown of ATP). Our results are consistent with the
      microtubule-based motility hypothesis of spermatid translocation.

PMID- 10084983
TI  - Rat testis motor proteins associated with spermatid translocation (dynein) and
      spermatid flagella (kinesin-II).
AB  - In this study, we report sites in the seminiferous epithelium of the rat testis
      that are immunoreactive with antibodies to the intermediate chain of cytoplasmic
      dynein and kinesin II. The study was done to determine whether or not microtubule
      dependent motor proteins are present in Sertoli cell regions involved with
      spermatid translocation. Sections and epithelial fragments of perfusion-fixed rat
      testis were probed with an antibody (clone 74.1) to the intermediate chain of
      cytoplasmic dynein (IC74) and to kinesin-II. Labeling with the antibody to
      cytoplasmic dynein was dramatically evident in Sertoli cell regions surrounding
      apical crypts containing attached spermatids and known to contain unique
      intercellular attachment plaques. The antibody to kinesin II reacted only with
      spermatid tails. The levels of cytoplasmic dynein visible on immunoblots of
      supernatants collected from spermatid/junction complexes treated with an actin
      severing enzyme (gelsolin) were greater than those of controls, indicating that
      at least some of the dynein may have been associated with Sertoli cell junction
      plaques attached to spermatids. Results are consistent with the conclusion that
      an isoform of cytoplasmic dynein may be responsible for the apical translocation
      of elongate spermatids that occurs before sperm release. Also, this is the first
      report of kinesin-II in mammalian spermatid tails.

PMID- 10084984
TI  - Febrile-range temperature modifies early systemic tumor necrosis factor alpha
      expression in mice challenged with bacterial endotoxin.
AB  - Fever improves survival in acute infections, but the effects of increased core
      temperature on host defenses are poorly understood. Tumor necrosis factor alpha
      (TNF-alpha) is an early activator of host defenses and a major endogenous
      pyrogen. TNF-alpha expression is essential for survival in bacterial infections
      but, if disregulated, can cause tissue injury. In this study, we show that
      passively increasing core temperature in mice from the basal (36.5 to 37.5
      degrees C) to the febrile (39.5 to 40 degrees C) range modifies systemic TNF
      alpha expression in response to bacterial endotoxin (lipopolysaccharide). The
      early TNF-alpha secretion rate is enhanced, but the duration of maximal TNF-alpha
      production is shortened. We identified Kupffer cells as the predominant source of
      the excess TNF-alpha production in the warmer animals. The enhanced early TNF
      alpha production observed at the higher temperature in vivo could not be
      demonstrated in isolated Kupffer cells or in precision-cut liver slices in vitro,
      indicating the participation of indirect pathways. Therefore, expression of the
      endogenous pyrogen TNF-alpha is regulated by increments in core temperature
      during fever, generating an enhanced early, self-limited TNF-alpha pulse.

PMID- 10084985
TI  - Chemokine secretion of human cells in response to Toxoplasma gondii infection.
AB  - The ubiquitous protozoan parasite Toxoplasma gondii is a major cause of morbidity
      and mortality in neonates and immunocompromised hosts. Both acute invasion and
      reactivation of latent infection result in an inflammatory reaction with
      lymphocytes, macrophages, and neutrophils. The mechanisms responsible for
      triggering the local host response to toxoplasmosis are not fully understood.
      Infection of monolayers of human HeLa epithelial cells and fibroblasts with T.
      gondii resulted in a marked increase in the expression of interleukin-8 (IL-8)
      specific mRNA and secretion of the proinflammatory and chemoattractant cytokines
      interleukin-8 (IL-8), GROalpha, and MCP-1. Host cell invasion and lysis were
      required for this response, as tachyzoite lysates alone had no effect on IL-8
      secretion. IL-8 release was dependent on the release of soluble host cell
      factors: IL-1alpha in HeLa cells and an additional mediator in fibroblasts. HT-29
      epithelial cells, which lack IL-1alpha or another IL-8-inducing activity, did not
      release IL-8 after infection, although they were efficiently infected with T.
      gondii and increased IL-8 secretion in response to added IL-1alpha. These data
      suggest that proinflammatory chemokine secretion is an important host cell
      response to toxoplasmosis and that the release of IL-1alpha and other mediators
      from lysed host cells is critical for this chemokine response.

PMID- 10084986
TI  - NF-kappaB1 (p50) is upregulated in lipopolysaccharide tolerance and can block
      tumor necrosis factor gene expression.
AB  - Monocytes respond to lipopolysaccharide (LPS) stimulation with a rapid expression
      of the tumor necrosis factor (TNF) gene. Upon repeated LPS stimulation there is,
      however, little production of TNF mRNA and protein; i.e., the cells are tolerant
      to LPS. Analysis of NF-kappaB proteins in gel shift assays demonstrated that the
      DNA binding activity that is induced by LPS stimulation in tolerant cells
      consists mainly of p50-p50 homodimers. Since p50 can bind to DNA but lacks a
      transactivation domain, this may explain the blockade of TNF gene expression. We
      now show that in the monocytic cell line Mono Mac 6, this inability to respond
      can be largely ascribed to NF-kappaB, since a reporter construct directed by a
      trimeric NF-kappaB motif is strongly transactivated by LPS stimulation of naive
      cells whereas LPS-tolerant cells exhibit only low activity. Also, Western blot
      analyses of proteins extracted from purified nuclei showed mobilization of
      threefold-higher levels of p50 protein in tolerant compared to naive cells, while
      mobilization of p65 was unaltered. Overexpression of p50 in HEK 293 cells
      resulted in a strong reduction of p65-driven TNF promoter activity at the levels
      of both luciferase mRNA and protein. These data support the concept that an
      upregulation of p50 is instrumental in LPS tolerance in human monocytes.

PMID- 10084987
TI  - The alternative sigma factor, sigmaE, is critically important for the virulence
      of Salmonella typhimurium.
AB  - In Escherichia coli, extracytoplasmic stress is partially controlled by the
      alternative sigma factor, RpoE (sigmaE). In response to environmental stress or
      alteration in the protein content of the cell envelope, sigmaE upregulates the
      expression of a number of genes, including htrA. It has been shown that htrA is
      required for intramacrophage survival and virulence in Salmonella typhimurium. To
      investigate whether sigmaE-regulated genes other than htrA are involved in
      salmonella virulence, we inactivated the rpoE gene of S. typhimurium SL1344 by
      allelic exchange and compared the phenotype of the mutant (GVB311) in vitro and
      in vivo with its parent and an isogenic htrA mutant (BRD915). Unlike E. coli,
      sigmaE is not required for the growth and survival of S. typhimurium at high
      temperatures. However, GVB311 did display a defect in its ability to utilize
      carbon sources other than glucose. GVB311 was more sensitive to hydrogen
      peroxide, superoxide, and antimicrobial peptides than SL1344 and BRD915. Although
      able to invade both macrophage and epithelial cell lines normally, the rpoE
      mutant was defective in its ability to survive and proliferate in both cell
      lines. The effect of the rpoE mutation on the intracellular behavior of S.
      typhimurium was greater than that of the htrA mutation. Both GVB311 and BRD915
      were highly attenuated in mice. Neither strain was able to kill mice via the oral
      route, and the 50% lethal dose (LD50) for both strains via the intravenous (i.v.)
      route was very high. The i.v. LD50s for SL1344, BRD915, and GVB311 were <10, 5.5
      x 10(5), and 1.24 x 10(7) CFU, respectively. Growth in murine tissues after oral
      and i.v. inoculation was impaired for both the htrA and rpoE mutant, with the
      latter mutant being more severely affected. Neither mutant was able to
      translocate successfully from the Peyer's patches to other organs after oral
      infection or to proliferate in the liver and spleen after i.v. inoculation.
      However, the htrA mutant efficiently colonized the livers and spleens of mice
      infected i.v., but the rpoE mutant did not. Previous studies have shown that
      salmonella htrA mutants are excellent live vaccines. In contrast, oral
      immunization of mice with GVB311 was unable to protect any of the mice from oral
      challenge with SL1344. Furthermore, i.v. immunization with a large dose (
      approximately 10(6) CFU) of GVB311 protected less than half of the orally
      challenged mice. Thus, our results indicate that genes in the sigmaE regulon
      other than htrA play a critical role in the virulence and immunogenicity of S.
      typhimurium.

PMID- 10084988
TI  - Phase variations of the Mycoplasma penetrans main surface lipoprotein increase
      antigenic diversity.
AB  - Mycoplasma penetrans is a recently identified mycoplasma, isolated from urine
      samples collected from human immunodeficiency virus (HIV)-infected patients. Its
      presence is significantly associated with HIV infection. The major antigen
      recognized during natural and experimental infections is an abundant P35
      lipoprotein which, upon extraction, segregates in the Triton X-114 detergent
      phase and is the basis of M. penetrans-specific serological assays. We report
      here that the P35 antigen undergoes spontaneous and reversible phase variation at
      high frequency, leading to heterogeneous populations of mycoplasmas, even when
      derived from a clonal lineage. This variation was found to be determined at the
      transcription level, and although this property is not unique among the members
      of the class Mollicutes, the mechanism by which it occurs in M. penetrans differs
      from those previously described for other Mycoplasma species. Indeed, the P35
      phase variation was due neither to a p35 gene rearrangement nor to point
      mutations within the gene itself or its promoter. The P35 phase variation in the
      different variants obtained was concomitant with modifications in the pattern of
      other expressed lipoproteins, probably due to regulated expression of selected
      members of a gene family which was found to potentially encode similar
      lipoproteins. M. penetrans variants could be selected on the basis of their lack
      of colony immunoreactivity with a polyclonal antiserum against a Triton X-114
      extract, strongly suggesting that the mechanisms involved in altering surface
      antigen expression might allow evasion of the humoral immune response of the
      infected host.

PMID- 10084989
TI  - Microbiological and inflammatory effects of murine recombinant interleukin-10 in
      two models of polymicrobial peritonitis in rats.
AB  - A protective effect of interleukin-10 (IL-10) against the development of lethal
      shock has been demonstrated in various animal models. In contrast, the
      immunosuppressant properties of this mediator have been minimally evaluated in
      low-mortality models of infections. The clinical, microbiological, and
      inflammatory effects of murine recombinant IL-10 (mrIL-10) therapy were evaluated
      in two models of peritonitis in rats, which differed in the degree of severity of
      peritoneal inflammation 3 days after inoculation of Escherichia coli and
      Bacteroides fragilis with or without Enterococcus faecalis. The severity of the
      disease remained unchanged compared to that in control animals. A dose-related
      decrease in the peritoneal phagocyte count was observed in the treated groups
      compared to the counts in control animals. The subsequent experiments were
      performed exclusively in the mixed gram-positive-gram negative model, which
      exhibits an intense and prolonged inflammatory response with similar criteria.
      The early effects of mrIL-10 (evaluated 6 h after inoculation), repeated
      injections of mrIL-10 (four doses injected from 0 to 9 h after bacterial
      challenge), and pretreatment (two doses injected 6 and 3 h before inoculation)
      were evaluated. The clinical and microbiological parameters remained unchanged in
      the treated animals. Decreases in the peritoneal phagocyte count and the
      peritoneal concentration of tumor necrosis factor were observed following
      repeated injections of mrIL-10. In summary, our data suggest that mrIL-10 does
      not worsen the manifestations of sepsis. However, these results need to be
      confirmed in clinical practice.

PMID- 10084990
TI  - Isolation of Enterococcus faecalis clinical isolates that efficiently adhere to
      human bladder carcinoma T24 cells and inhibition of adhesion by fibronectin and
      trypsin treatment.
AB  - The adherence of Enterococcus faecalis strains to human T24 cells was examined by
      scanning electron microscopy. Five highly adhesive strains were identified from
      30 strains isolated from the urine of patients with urinary tract infections. No
      efficiently adhesive strains were found among the 30 strains isolated from the
      feces of healthy students. The five isolated strains also adhered efficiently to
      human bladder epithelial cells. Analysis of restriction endonuclease-digested
      plasmid DNAs and chromosome DNAs showed that the five strains were different
      strains isolated from different patients. The adhesiveness of these strains was
      inhibited by treatment with fibronectin or trypsin, implying that a specific
      protein (adhesin) on the bacterial cell surface mediates adherence to fibronectin
      on the host cell surfaces, and the adhesin differs from the reported adhesins.

PMID- 10084991
TI  - Antigen-specific B-cell unresponsiveness induced by chronic Mycobacterium avium
      subsp. paratuberculosis infection of cattle.
AB  - Mycobacterium avium subsp. paratuberculosis infection of cattle results in a
      chronic granulomatous enteritis. Clinical disease (i.e., cachexia, diarrhea, and
      high fecal bacterial counts) is preceded by a lengthy subclinical stage of
      disease. The immunologic mechanisms associated with the progression of infected
      cattle from subclinical to clinical disease are unclear. In this study, a cell
      proliferation assay was used in combination with flow cytometry to compare
      peripheral blood lymphocyte responses of cattle with subclinical paratuberculosis
      to responses of cattle with clinical paratuberculosis. B cells from cattle with
      subclinical disease proliferated vigorously upon stimulation with M. avium subsp.
      paratuberculosis antigen, with up to 12.4% of the total B cells responding.
      However, B cells from cattle with clinical disease did not proliferate upon
      antigen stimulation despite good proliferation in response to concanavalin A
      stimulation. In addition, these animals had high percentages of peripheral blood
      B cells. B cells from noninfected animals did not proliferate upon M. avium
      subsp. paratuberculosis antigen stimulation. Thus, it appears that B-cell
      proliferation is a sensitive indicator of subclinical Johne's disease.
      Furthermore, the immunologic mechanisms responsible for the antigen-specific
      unresponsiveness of peripheral blood B cells may be significant in the eventual
      progression from subclinical to clinical Johne's disease in cattle.

PMID- 10084992
TI  - Interleukin-10 and antigen-presenting cells actively suppress Th1 cells in BALB/c
      mice infected with the filarial parasite Brugia pahangi.
AB  - Infection with the third-stage larvae (L3) of the filarial nematode Brugia
      results in a Th2-biased immune response in mice and humans. Previously we have
      shown that the production of interleukin 4 (IL-4) is critical for down-regulating
      polyclonal Th1 responses in L3-infected mice. However, the in vitro
      neutralization of IL-4 did not fully recover the defective polyclonal Th1
      responses, nor did it result in the production of any antigen (Ag)-specific Th1
      cytokines, suggesting that perhaps infection with L3 does not result in priming
      of Th1 cells in vivo. In this study, we analyzed the role of IL-10 and Ag
      presenting cells (APCs) in the spleen as additional factors controlling the Th2
      bias in infected mice. Our data show that IL-10 and APCs also contribute to the
      suppression of mitogen-driven Th1 responses of spleen cells from infected mice.
      In addition, the neutralization of IL-10 or the replacement of the resident APC
      population from spleen cell cultures resulted in the production of Ag-specific
      Th1 cytokines. Irradiated spleen cells from either L3-infected or uninfected mice
      were able to restore Ag-specific Th1 responses in vitro. Therefore, it appears
      that Brugia-reactive Th1 cells are primed following infection with L3, but are
      actively suppressed in vivo by a mechanism that involves IL-10 and the resident
      APC population, but not IL-4. These results indicate that a complex interplay of
      cytokines and cell populations underscores the Th2-polarized response in L3
      infected mice.

PMID- 10084993
TI  - Immunity to Chlamydia trachomatis mouse pneumonitis induced by vaccination with
      live organisms correlates with early granulocyte-macrophage colony-stimulating
      factor and interleukin-12 production and with dendritic cell-like maturation.
AB  - As is true for other intracellular pathogens, immunization with live Chlamydia
      trachomatis generally induces stronger protective immunity than does immunization
      with inactivated organism. To investigate the basis for such a difference, we
      studied immune responses in BALB/c mice immunized with viable or UV-killed C.
      trachomatis mouse pneumonitis (MoPn). Strong, acquired resistance to C.
      trachomatis infection was elicited by immunization with viable but not dead
      organisms. Immunization with viable organisms induced high levels of antigen
      specific delayed-type hypersensitivity (DTH), gamma interferon production, and
      immunoglobulin A (IgA) responses. Immunization with inactivated MoPn mainly
      induced interleukin-10 (IL-10) production and IgG1 antibody without IgA or DTH
      responses. Analysis of local early cytokine and cellular events at days 3, 5, and
      7 after peritoneal cavity immunization showed that high levels of granulocyte
      macrophage colony-stimulating factor and IL-12 were detected with viable but not
      inactivated organisms. Furthermore, enrichment of a dendritic cell (DC)-like
      population was detected in the peritoneal cavity only among mice immunized with
      viable organisms. The results suggest that early differences in inducing
      proinflammatory cytokines and activation and differentiation of DCs may be the
      key mechanism underlying the difference between viable and inactivated organisms
      in inducing active immunity to C. trachomatis infection.

PMID- 10084994
TI  - PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella
      spp.
AB  - As enteric pathogens, Salmonella spp. are resistant to the actions of bile.
      Salmonella typhimurium and Salmonella typhi strains were examined to better
      define the bile resistance phenotype. The MICs of bile for wild-type S.
      typhimurium and S. typhi were 18 and 12%, respectively, and pretreatment of log
      phase S. typhimurium with 15% bile dramatically increased bile resistance. Mutant
      strains of S. typhimurium and S. typhi lacking the virulence regulator PhoP-PhoQ
      were killed at significantly lower bile concentrations than wild-type strains,
      while strains with constitutively active PhoP were able to survive prolonged
      incubation with bile at concentrations of >60%. PhoP-PhoQ was shown to mediate
      resistance specifically to the bile components deoxycholate and conjugated forms
      of chenodeoxycholate, and the protective effect was not generalized to other
      membrane-active agents. Growth of both S. typhimurium and S. typhi in bile and in
      deoxycholate resulted in the induction or repression of a number of proteins,
      many of which appeared identical to PhoP-PhoQ-activated or -repressed products.
      The PhoP-PhoQ regulon was not induced by bile, nor did any of the 21 PhoP
      activated or -repressed genes tested play a role in bile resistance. However, of
      the PhoP-activated or -repressed genes tested, two (prgC and prgH) were
      transcriptionally repressed by bile in the medium independent of PhoP-PhoQ. These
      data suggest that salmonellae can sense and respond to bile to increase
      resistance and that this response likely includes proteins that are members of
      the PhoP regulon. These bile- and PhoP-PhoQ-regulated products may play an
      important role in the survival of Salmonella spp. in the intestine or
      gallbladder.

PMID- 10084995
TI  - Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide on
      human gingival fibroblasts and monocytes in a CD14-dependent manner.
AB  - CD14 has been implicated as a receptor of lipoteichoic acid (LTA) and other
      bacterial components as well as lipopolysaccharide (LPS). Since the structures of
      LTAs from various gram-positive bacteria are heterogeneous, we analyzed the
      effects of LTAs on the secretion of interleukin-8 (IL-8) by high- and low-CD14
      expressing (CD14(high) and CD14(low)) human gingival fibroblasts (HGF). While
      Bacillus subtilis LTA had an IL-8-inducing effect on CD14(high) HGF which was
      considerably weaker than that of LPS, Streptococcus sanguis and Streptococcus
      mutans LTAs had practically no effect on the cells. B. subtilis LTA had only a
      weak effect on CD14(low) HGF, as did LPS. S. sanguis and S. mutans LTAs at a
      1,000-fold excess each completely inhibited the IL-8-inducing activities of both
      LPS and a synthetic lipid A on CD14(high) HGF. The effect of LPS was also
      inhibited by the presence of an LPS antagonist, synthetic lipid A precursor IVA
      (LA-14-PP), with a 100-fold higher potency than S. sanguis and S. mutans LTAs and
      by anti-CD14 monoclonal antibody (MAb). S. sanguis and S. mutans LTAs, LA-14-PP,
      and anti-CD14 MAb had no significant effect on phorbol myristate acetate
      stimulated IL-8 secretion by HGF. These LTAs also inhibited the IL-8-inducing
      activity of B. subtilis LTA on CD14(high) HGF, as did LA-14-PP and anti-CD14 MAb.
      The antagonistic and agonistic functions of LTAs were also observed with human
      monocytes. Binding of fluorolabeled LPS to human monocytes was inhibited by S.
      sanguis LTA, although the inhibition was 100 times weaker than that of LPS
      itself, and anti-CD14 MAb inhibited fluorolabeled LPS and S. sanguis LTA binding.
      Binding of LTAs to CD14 was also observed with nondenaturing polyacrylamide gel
      electrophoresis. These results indicate that LTAs act as antagonists or agonists
      via a CD14-dependent mechanism, probably due to the heterogeneous structure of
      LTAs, and that an antagonistic LTA might be a useful agent for suppressing the
      periodontal disease caused by gram-negative bacteria.

PMID- 10084996
TI  - Lipopolysaccharide enhances the production of vascular endothelial growth factor
      by human pulp cells in culture.
AB  - We investigated whether vascular endothelial growth factor (VEGF) production by
      human pulp cells (HPC) is regulated by lipopolysaccharide (LPS) in relation to
      the pathogenesis of pulpitis. Although HPC incubated with medium alone only
      marginally expressed VEGF mRNA and produced a low level of VEGF as detected by
      enzyme-linked immunosorbent assay, the VEGF mRNA expression and VEGF production
      were markedly enhanced upon stimulation with LPS from Escherichia coli.
      Prevotella intermedia LPS, phorbol 12-myristate 13-acetate, and interleukin-6
      also induced VEGF mRNA expression in HPC. A simian virus 40-infected HPC line
      also exhibited increased VEGF mRNA expression in response to E. coli LPS, but
      lung and skin fibroblasts did not. Fetal bovine serum (FBS) increased the
      sensitivity of HPC to LPS in a dose-dependent manner. HPC did not express
      membrane CD14 on their surfaces. However, the anti-CD14 monoclonal antibody MY4
      inhibited VEGF induction upon stimulation with LPS in HPC cultures in the
      presence of 10% FBS but not in the absence of FBS. LPS augmented the VEGF
      production in HPC cultures in the presence of recombinant human soluble CD14
      (sCD14). To clarify the mechanisms of VEGF induction by LPS, we examined the
      possible activation of the transcription factor AP-1 in HPC stimulated with LPS,
      by a gel mobility shift assay. AP-1 activation in HPC was clearly observed,
      whereas that in skin fibroblasts was not. The AP-1 inhibitor curcumin strongly
      inhibited LPS-induced VEGF production in HPC cultures. In addition, a protein
      synthesis inhibitor, cycloheximide, inhibited VEGF mRNA accumulation in response
      to LPS. These results suggest that the enhanced production of VEGF in HPC induced
      by LPS takes place via an sCD14-dependent pathway which requires new protein
      synthesis and is mediated in part through AP-1 activation.

PMID- 10084997
TI  - Defensins impair phagocytic killing by neutrophils in biomaterial-related
      infection.
AB  - The implantation of foreign material carries a risk of infection which frequently
      is resistant to all treatment short of removing the implant. We have previously
      shown that these materials activate neutrophils by contact, leading to production
      of oxygen free radicals accompanied by release of granule products. Such
      activation further results in depletion of local host defenses, including the
      capacity of biomaterial-activated neutrophils to kill bacteria. Among the granule
      products released from neutrophils are small cationic antibacterial peptides
      (human neutrophil peptides [HNP]) known as defensins. Here we tested the
      hypothesis that defensins, released from activated neutrophils onto the surface
      of biomaterials, might play a role in the deactivation of subsequent neutrophil
      populations. Incubation of neutrophils with purified HNP resulted in a dose
      related impairment of stimulus-induced oxygen radical production and of
      phagocytic killing. Furthermore, fresh neutrophils added to biomaterial
      associated neutrophils exhibited impaired phagocytic killing. This impairment
      could be abrogated by antibody to HNP but not by an irrelevant antibody. Taken
      together, these observations support the idea that neutrophils activated at a
      material surface can create, by means of HNP release, an environment hostile to
      their microbicidal function and that of their infiltrating brethren.

PMID- 10084998
TI  - Immunological characterization of a protective antigen of Erysipelothrix
      rhusiopathiae: identification of the region responsible for protective immunity.
AB  - The gene encoding a protective protein antigen of the gram-positive bacterium
      Erysipelothrix rhusiopathiae, an important veterinary pathogen responsible for
      erysipelas in swine and a variety of diseases in animals, was cloned and
      sequenced. The gene encodes a polypeptide of 597 amino acids plus a putative
      signal sequence of 29 amino acids, resulting in a mature protein with a molecular
      mass of 69,017 Da. Sequence analysis of the gene product revealed a C-terminal
      region composed of nine tandem repeats of 20 amino acids and a total sequence
      that is nearly identical to that of the 64-kDa cell surface protein (SpaA) of the
      bacterium. Because of this similarity, the protein was designated SpaA.1. In this
      study, we examined whether the SpaA.1 protein could induce protective antibodies
      and whether we could identify the region involved in protective immunity. Both
      the mature SpaA.1 protein and its C-terminal repeat region, but not the N
      terminal segment, were expressed in Escherichia coli and purified as a histidine
      tagged fusion recombinant protein. Rabbit antiserum raised against the mature
      SpaA.1 protein passively protected mice from lethal challenge with a virulent
      homologous strain, Fujisawa-SmR, suggesting that protection is mediated by
      humoral antibodies. To determine which domain of the SpaA.1 protein is
      responsible for the observed protection, mice were actively immunized with either
      the mature SpaA. 1 protein or the C-terminal repeat region and then challenged
      with Fujisawa-SmR. The result showed that mice immunized with the mature SpaA.1
      protein, but not the C-terminal repeat region, were protected, suggesting that
      the protection-eliciting epitope(s) is located within the N-terminal two-thirds
      of the SpaA.1 molecule. This was confirmed by passive immunization experiments in
      which the protective activity of rabbit antiserum, raised against mature SpaA. 1
      protein, was not abolished by absorption with the purified recombinant C-terminal
      repeat region. In addition, antibodies specific for the C-terminal repeat region
      were unable to protect mice from lethal challenge. These results show that the N
      terminal two-thirds of the SpaA.1 molecule may constitute a good vaccine
      candidate against erysipelas.

PMID- 10084999
TI  - Molecular characterization of a Haemaphysalis longicornis tick salivary gland
      associated 29-kilodalton protein and its effect as a vaccine against tick
      infestation in rabbits.
AB  - The use of tick vaccines in mammalian hosts has been shown to be the most
      promising alternative tick control method to current use of acaricides, which
      suffers from a number of limitations. However, the success of this method is
      dependent on the identification, cloning, and in vitro expression of tick
      molecules involved in the mediation of key physiological roles with respect to
      the biological success of a tick as a vector and pest. We have sequenced and
      characterized a Haemaphysalis longicornis tick salivary gland-associated cDNA
      coding for a 29-kDa extracellular matrix-like protein. This protein is expressed
      in both unfed and fed immature and mature H. longicornis ticks. The predicted
      amino acid sequence of p29 shows high homology to sequences of some known
      extracellular matrix like-proteins with the structural conservation similar to
      all known collagen proteins. Immunization with the recombinant p29 conferred a
      significant protective immunity in rabbits, resulting in reduced engorgement
      weight for adult ticks and up to 40 and 56% mortality in larvae and nymphs that
      fed on the immunized rabbits. We speculate that this protein is associated with
      formation of tick cement, a chemical compound that enables the tick to remain
      attached to the host, and suggest a role for p29 as a candidate tick vaccine
      molecule for the control of ticks. We have discussed our findings with respect to
      the search of tick molecules for vaccine candidates.

PMID- 10085000
TI  - The p47(phox-/-) mouse model of chronic granulomatous disease has normal
      granuloma formation and cytokine responses to Mycobacterium avium and Schistosoma
      mansoni eggs.
AB  - Chronic granulomatous disease (CGD) is a genetic disorder of NADPH oxidase in
      which phagocytes are defective in generating reactive oxidants. CGD patients
      suffer from recurrent infections and exuberant and persistent tissue granuloma
      formation. We hypothesized that abnormal granulomata in CGD may result from
      aberrant T-cell-mediated cytokine responses. To assess Th-1-type cytokine
      responses and granulomata, we challenged p47(phox-/-) and wild-type mice with
      avirulent (SmD) or virulent (SmT) variants of Mycobacterium avium 2-151. To
      assess Th-2-type cytokine responses and granulomata, we used Schistosoma mansoni
      eggs (SME). Mononuclear cells were harvested, and cytokine responses were
      determined by enzyme-linked immunosorbent assay or reverse transcriptase PCR.
      Following SmD or SmT challenge, splenocytes from p47(phox-/-) and wild-type mice
      generated similar polar Th-1 responses (increased levels of gamma interferon and
      basal levels of interleukin 4 [IL-4] and IL-5). By 8 weeks after SmT challenge,
      exuberant splenic granulomata developed in p47(phox-/-) and wild-type mice. After
      SME challenge, thoracic lymph node mononuclear cells from p47(phox-/-) and wild
      type mice generated similar mixed Th-1 and Th-2 cytokine responses to SME antigen
      and concanavalin A. Peak lung granuloma sizes and rates of regression were
      similar in p47(phox-/-) and wild-type mice. These results suggest that exuberant
      granulomatous inflammation in CGD is probably not the result of skewing of T-cell
      responses toward the Th-1 or Th-2 pole. Appropriate regression of established
      tissue granulomata in p47(phox-/-) mice challenged with SME suggests that
      abnormal granuloma formation in CGD is stimulus dependent and is not an invariant
      feature of the disease.

PMID- 10085001
TI  - Intracellular tryptophan pool sizes may account for differences in gamma
      interferon-mediated inhibition and persistence of chlamydial growth in polarized
      and nonpolarized cells.
AB  - Gamma interferon (IFN-gamma) is an important factor in the modulating inhibition
      of intracellular chlamydial growth and persistence. In human epithelial cells and
      macrophages, this inhibition is the result of depletion of the essential amino
      acid tryptophan via the IFN-gamma-induced enzyme indoleamine 2, 3-dioxygenase.
      Under these conditions, chlamydiae must successfully compete with the host cell
      for limited resources in order to maintain viability. We provide evidence to
      support the hypothesis that the host cell polarization state influences the host
      pathogen interplay and outcome of IFN-gamma-mediated inhibition. In polarized
      cells, intracellular soluble tryptophan pools were larger than those in
      nonpolarized cells despite only small differences in the initial uptake rate of
      this amino acid compared to that in nonpolarized cells. Furthermore, in Chlamydia
      trachomatis-infected cells, the amounts of tryptophan consumed by the organisms
      were similar for cells grown in either state. We propose that intracellular
      tryptophan pool sizes can account for differences in IFN-gamma-mediated
      chlamydial persistence and growth inhibition in polarized and nonpolarized cells.
      Collectively, these results argue that polarized cell models, which more
      accurately reflect the conditions in vivo, may be more relevant than
      conventionally cultured cells in the study of intimate intracellular host
      parasite interactions.

PMID- 10085002
TI  - Construction and characterization of mutations within the Klebsiella mrkD1P gene
      that affect binding to collagen type V.
AB  - The fimbria-associated MrkD1P protein mediates adherence of type 3 fimbriate
      strains of Klebsiella pneumoniae to collagen type V. Currently, three different
      MrkD adhesins have been described in Klebsiella species, and each possesses a
      distinctive binding pattern. Therefore, the binding abilities of mutants
      possessing defined mutations within the mrkD1P gene were examined in order to
      determine whether specific regions of the adhesin molecule were responsible for
      collagen binding. Both site-directed and chemically induced mutations were
      constructed within mrkD1P, and the ability of the gene products to be
      incorporated into fimbrial appendages or bind to collagen was determined. Binding
      to type V collagen was not associated solely with one particular region of the
      MrkD1P protein, and two classes of nonadhesive mutants were isolated. In one
      class of mutants, the MrkD adhesin was not assembled into the fimbrial shaft,
      whereas in the second class of mutants, the adhesin was associated with fimbriae
      but did not bind to collagen. Both hemagglutinating and collagen-binding
      activities were associated with the MrkD1P molecule, since P pili and type 3
      fimbriae carrying adhesive MrkD proteins exhibited identical binding properties.

PMID- 10085003
TI  - Transformed Toxoplasma gondii tachyzoites expressing the circumsporozoite protein
      of Plasmodium knowlesi elicit a specific immune response in rhesus monkeys.
AB  - Toxoplasma gondii tachyzoites were transformed with the coding sequence of the
      circumsporozoite (CS) protein of the primate malaria parasite Plasmodium
      knowlesi. A single inoculation of live transformed tachyzoites elicited an
      antibody response directed against the immunodominant repeat epitope (EQPAAGAGG)2
      of the P. knowlesi CS protein in rhesus monkeys. Notably, these animals failed to
      show a positive serum conversion against T. gondii. Antibodies against Toxoplasma
      antigens were detected only after a second inoculation with a higher number of
      transformed tachyzoites. This boost induced an increased antibody response
      against the P. knowlesi CS protein associated with immunoglobulin class
      switching, thus demonstrating the establishment of immunological memory. These
      results indicate that the Toxoplasma-derived CS protein is efficiently recognized
      by the monkey immune system and represents an immunodominant antigen in
      transformed parasites.

PMID- 10085004
TI  - Identification of pneumococcal surface protein A as a lactoferrin-binding protein
      of Streptococcus pneumoniae.
AB  - Lactoferrin (Lf), an iron-sequestering glycoprotein, predominates in mucosal
      secretions, where the level of free extracellular iron (10(-18) M) is not
      sufficient for bacterial growth. This represents a mechanism of resistance to
      bacterial infections by prevention of colonization of the host by pathogens. In
      this study we were able to show that Streptococcus pneumoniae specifically
      recognizes and binds the iron carrier protein human Lf (hLf). Pretreatment of
      pneumococci with proteases reduced hLf binding significantly, indicating that the
      hLf receptor is proteinaceous. Binding assays performed with 63 clinical isolates
      belonging to different serotypes showed that 88% of the tested isolates
      interacted with hLf. Scatchard analysis showed the existence of two hLf-binding
      proteins with dissociation constants of 5.7 x 10(-8) and 2.74 x 10(-7) M. The
      receptors were purified by affinity chromatography, and internal sequence
      analysis revealed that one of the S. pneumoniae proteins was homologous to
      pneumococcal surface protein A (PspA). The function of PspA as an hLf-binding
      protein was confirmed by the ability of purified PspA to bind hLf and to
      competitively inhibit hLf binding to pneumococci. S. pneumoniae may use the hLf
      PspA interaction to overcome the iron limitation at mucosal surfaces, and this
      might represent a potential virulence mechanism.

PMID- 10085005
TI  - Immunization of mice with DNA-based Pfs25 elicits potent malaria transmission
      blocking antibodies.
AB  - Immunological intervention, in addition to vector control and malaria
      chemotherapy, will be needed to stop the resurgence of malaria, a disease with a
      devastating impact on the health of 300 to 500 million people annually. We have
      pursued a vaccination strategy, based on DNA immunization in mice with genes
      encoding two antigens present on the sexual stages of Plasmodium falciparum,
      Pfs25 and Pfg27, to induce biologically important antibodies that can block
      development of the parasite in the Anopheles mosquito and thus transmission of
      the disease. DNA encoding Pfs25 when administered by the intramuscular route,
      either alone or with DNA encoding Pfg27, had the most potent transmission
      blocking effects, resulting in up to a 97% decrease in oocyst numbers in mosquito
      midguts and a 75% decrease in rate of infection. Immunization with DNA encoding a
      Pfg27-Pfs25 fusion protein was less effective and DNA encoding Pfg27 elicited
      antibodies in sera that had only modest effects on the infectivity of the
      parasite. These results show for the first time that DNA vaccination can result
      in potent transmission-blocking antibodies in mice and suggest that the Pfs25
      gene should be included as part of a multicomponent DNA vaccine.

PMID- 10085006
TI  - In vivo expression and immunoadjuvancy of a mutant of heat-labile enterotoxin of
      Escherichia coli in vaccine and vector strains of Vibrio cholerae.
AB  - Vibrio cholerae secretes cholera toxin (CT) and the closely related heat-labile
      enterotoxin (LT) of Escherichia coli, the latter when expressed in V. cholerae.
      Both toxins are also potent immunoadjuvants. Mutant LT molecules that retain
      immunoadjuvant properties while possessing markedly diminished enterotoxic
      activities when expressed by E. coli have been developed. One such mutant LT
      molecule has the substitution of a glycine residue for arginine-192 [LT(R192G)].
      Live attenuated strains of V. cholerae that have been used both as V. cholerae
      vaccines and as vectors for inducing mucosal and systemic immune responses
      directed against expressed heterologous antigens have been developed. In order to
      ascertain whether LT(R192G) can act as an immunoadjuvant when expressed in vivo
      by V. cholerae, we introduced a plasmid (pCS95) expressing this molecule into
      three vaccine strains of V. cholerae, Peru2, ETR3, and JRB14; the latter two
      strains contain genes encoding different heterologous antigens in the chromosome
      of the vaccine vectors. We found that LT(R192G) was expressed from pCS95 in vitro
      by both E. coli and V. cholerae strains but that LT(R192G) was detectable in the
      supernatant fraction of V. cholerae cultures only. In order to assess potential
      immunoadjuvanticity, groups of germfree mice were inoculated with the three V.
      cholerae vaccine strains alone and compared to groups inoculated with the V.
      cholerae vaccine strains supplemented with purified CT as an oral immunoadjuvant
      or V. cholerae vaccine strains expressing LT(R192G) from pCS95. We found that
      mice continued to pass stool containing V. cholerae strains with pCS95 for at
      least 4 days after oral inoculation, the last day evaluated. We found that
      inoculation with V. cholerae vaccine strains containing pCS95 resulted in anti
      LT(R192G) immune responses, confirming in vivo expression. We were unable to
      detect immune responses directed against the heterologous antigens expressed at
      low levels in any group of animals, including animals that received purified CT
      as an immunoadjuvant. We were, however, able to measure increased vibriocidal
      immune responses against vaccine strains in animals that received V. cholerae
      vaccine strains expressing LT(R192G) from pCS95 compared to the responses in
      animals that received V. cholerae vaccine strains alone. These results
      demonstrate that mutant LT molecules can be expressed in vivo by attenuated
      vaccine strains of V. cholerae and that such expression can result in an
      immunoadjuvant effect.

PMID- 10085007
TI  - Differential protective efficacy of DNA vaccines expressing secreted proteins of
      Mycobacterium tuberculosis.
AB  - The development of more-effective antituberculosis vaccines would assist in the
      control of the global problem of infection with Mycobacterium tuberculosis. One
      recently devised vaccination strategy is immunization with DNA plasmids encoding
      individual microbial genes. Using the genes for the M. tuberculosis secreted
      proteins MPT64 (23 kDa), Ag85B (30 kDa), and ESAT-6 (6 kDa) as candidate
      antigens, DNA vaccines were prepared and tested for immunogenicity and protective
      efficacy in a murine model of aerosolized tuberculosis (TB). Intramuscular
      immunization with DNA-64 or DNA-85B resulted in the activation of CD4(+) T cells,
      which produce gamma interferon (IFN-gamma), and high titers of specific
      immunoglobulin G antibodies. Further, DNA-64 induced major histocompatibility
      complex class I-restricted CD8(+) cytotoxic T cells. The addition of a eukaryotic
      leader sequence to mpt64 did not significantly increase the T-cell or antibody
      response. Each of the three DNA vectors stimulated a significant reduction in the
      level of M. tuberculosis infection in the lungs of mice challenged 4 weeks after
      immunization, but not to the levels resulting after immunization with
      Mycobacterium bovis BCG. The vaccines showed a consistent hierarchy of
      protection, with the most effective being Ag85B, followed by ESAT-6 and then
      MPT64. Coimmunization with the three vectors resulted in a greater degree of
      protection than that induced by any single vector. This protective efficacy was
      associated with the emergence of IFN-gamma-secreting T cells earlier than in
      infected animals immunized with a control vector. The efficacy of these DNA
      vaccines suggests that multisubunit vaccination may contribute to future vaccine
      strategies against TB.

PMID- 10085008
TI  - Protein H, an antiphagocytic surface protein in Streptococcus pyogenes.
AB  - Surface-associated M protein is a major virulence factor in Streptococcus
      pyogenes which confers bacterial resistance to phagocytosis. However, many S.
      pyogenes strains also express additional structurally related so-called M-like
      proteins. The strain studied here is of the clinically important M1 serotype and
      expresses two structurally related surface proteins, the M1 protein and protein
      H. Mutants were generated that expressed only one or none of these proteins at
      the bacterial surface. For survival in human blood either protein H or M1 protein
      was sufficient, whereas the double mutant was rapidly killed. The protein-binding
      properties of protein H, M1 protein, and the mutants suggest that bacterial
      binding of immunoglobulin G and factor H or factor H-like protein 1, which are
      regulatory proteins in the complement system, contribute to the antiphagocytic
      property.

PMID- 10085009
TI  - The rgg gene of Streptococcus pyogenes NZ131 positively influences extracellular
      SPE B production.
AB  - Streptococcus pyogenes produces several extracellular proteins, including
      streptococcal erythrogenic toxin B (SPE B), also known as streptococcal pyrogenic
      exotoxin B and streptococcal proteinase. Several reports suggest that SPE B
      contributes to the virulence associated with S. pyogenes; however, little is
      known about its regulation. Nucleotide sequence data revealed the presence,
      upstream of the speB gene, of a gene, designated rgg, that was predicted to
      encode a polypeptide similar to previously described positive regulatory factors.
      The putative Rgg polypeptide of S. pyogenes NZ131 consisted of 280 amino acids
      and had a predicted molecular weight of 33,246. To assess the potential role of
      Rgg in the production of SPE B, the rgg gene was insertionally inactivated in S.
      pyogenes NZ131, which resulted in markedly decreased SPE B production, as
      determined both by immunoblotting and caseinolytic activity on agar plates.
      However, the production of other extracellular products, including streptolysin
      O, streptokinase, and DNase, was not affected. Complementation of the rgg mutant
      with an intact rgg gene copy in S. pyogenes NZ131 could restore SPE B production
      and confirmed that the rgg gene product is involved in the production of SPE B.

PMID- 10085010
TI  - An Arcanobacterium (Actinomyces) pyogenes mutant deficient in production of the
      pore-forming cytolysin pyolysin has reduced virulence.
AB  - Pyolysin (PLO), the hemolytic exotoxin expressed by Arcanobacterium (Actinomyces)
      pyogenes, is a member of the thiol-activated cytolysin family of bacterial
      toxins. Insertional inactivation of the plo gene results in loss of expression of
      PLO with a concomitant loss in hemolytic activity. The plo mutant, PLO-1, has an
      approximately 1. 8-log10 reduction in the 50% infectious dose compared to that
      for wild-type A. pyogenes in a mouse intraperitoneal infection model. Studies
      involving cochallenge of wild-type and PLO-1 bacteria resulted in recovery of
      similar numbers of both strains, suggesting that PLO production is required for
      survival in vivo. Recombinant, His-tagged PLO (His-PLO) is cytotoxic for mouse
      peritoneal macrophages and J774 cells in a dose-dependent manner. Protection
      against challenge with A. pyogenes could be afforded by vaccination with formalin
      inactivated His-PLO, suggesting that PLO is a host-protective antigen, as well as
      a virulence determinant.

PMID- 10085011
TI  - A novel 62-kilodalton egg antigen from Schistosoma mansoni induces a potent
      CD4(+) T helper cell response in the C57BL/6 mouse.
AB  - In infection with Schistosoma mansoni, hepatic granuloma formation is mediated by
      CD4(+) T helper (Th) cells sensitized to schistosomal egg antigens. There is
      considerable variation among infected individuals with respect to both severity
      of disease and the T-cell response to egg antigens. In the BL/6 mouse, the egg
      granulomas are relatively small and the relevant sensitizing egg antigens are
      largely unknown. We investigated the CD4(+) Th cell response of infected BL/6
      mice to egg antigens fractionated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and found a prominent lymphoproliferative response to be directed
      against a 62-kDa component. With the aid of a specific T-cell hybridoma, 4E6, the
      62-kDa antigen was isolated; following partial digestion with endoproteinase Glu
      C, an internal amino acid sequence was found to be identical with one present in
      the enzyme phosphoenolpyruvate carboxykinase (PEPCK) of the organisms
      Caenorhabditis elegans and Treponema pallidum and to differ by one residue from
      PEPCK of various other species. In CD4(+) Th cells from 7.5- 8.5-week-infected
      BL/6 mice, the purified 62-kDa molecule elicited a potent proliferative response
      which, based on cytokine analysis, was of a mixed Th-1 and Th-2 type. Our results
      reveal a novel egg antigen of particular prominence in the BL/6 mouse and suggest
      that the immune response in schistosomiasis is a product of sensitization to egg
      antigens that may vary considerably in immunogenicity from strain to strain.

PMID- 10085012
TI  - Lipopolysaccharides (LPS) of oral black-pigmented bacteria induce tumor necrosis
      factor production by LPS-refractory C3H/HeJ macrophages in a way different from
      that of Salmonella LPS.
AB  - Some lipopolysaccharide (LPS) preparations from S- or R-form members of the
      family Enterobacteriaceae and oral black-pigmented bacteria (Porphyromonas
      gingivalis and Prevotella intermedia) are known to activate LPS-refractory
      C3H/HeJ macrophages. When contaminating proteins are removed from R-form LPS of
      Enterobacteriaceae by repurification, however, this ability is lost. In the
      present study, we investigated the capacity of LPS from P. gingivalis, P.
      intermedia, Salmonella minnesota, and Salmonella abortusequi to induce production
      of tumor necrosis factor (TNF) in gamma interferon-primed C3H/HeJ macrophages
      before and after repurification. P. abortusequi S-LPS was fractionated by
      centrifugal partition chromatography into two LPS forms: SL-LPS, having
      homologous long O-polysaccharide chains, and SS-LPS having short oligosaccharide
      chains. Prior to repurification, all LPS forms except SL-LPS induced TNF
      production in both C3H/HeJ and C3H/HeN macrophages. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis showed that repurification removed
      contaminating protein from the preparations, and repurified SS-LPS and S.
      minnesota Ra-LPS no longer stimulated TNF production in C3H/HeJ macrophages,
      although C3H/HeN macrophages remained responsive. In contrast, repurified oral
      bacterial LPS retained the capacity to induce TNF production in C3H/HeJ
      macrophages. Oral bacterial LPS preparations also were not antagonized by excess
      inactive, repurified SL-LPS; Ra-LPS; Rhodobacter sphaeroides lipid A, a
      competitive LPS antagonist, or paclitaxel, an LPS agonist, and they were
      comparatively resistant to polymyxin B treatment. Nevertheless, oral bacterial
      LPS was less toxic to D-galactosamine-treated C3H/HeN mice than was LPS from
      Salmonella. These findings indicate that the active molecule(s) and mode of
      action of LPS from P. gingivalis and P. intermedia are quite different from those
      of LPS from Salmonella.

PMID- 10085013
TI  - Strain variation in glycosaminoglycan recognition influences cell-type-specific
      binding by lyme disease spirochetes.
AB  - Lyme disease, a chronic multisystemic disorder that can affect the skin, heart,
      joints, and nervous system is caused by Borrelia burgdorferi sensu lato. Lyme
      disease spirochetes were previously shown to bind glycosaminoglycans (GAGs). In
      the current study, the GAG-binding properties of eight Lyme disease strains were
      determined. Binding by two high-passage HB19 derivatives to Vero cells could not
      be inhibited by enzymatic removal of GAGs or by the addition of exogenous GAG.
      The other six strains, which included a different high-passage HB19 derivative
      (HB19 clone 1), were shown to recognize both heparan sulfate and dermatan sulfate
      in cell-binding assays, but the relative efficiency of binding to these two GAGs
      varied among the strains. Strains N40, CA20-2A, and PBi bound predominantly to
      heparan sulfate, PBo bound both heparan sulfate and dermatan sulfate roughly
      equally, and VS461 and HB19 clone 1 recognized primarily dermatan sulfate. Cell
      binding by strain HB19 clone 1 was inhibited better by exogenous dermatan sulfate
      than by heparin, whereas heparin was the better inhibitor of binding by strain
      N40. The GAG-binding preference of a Lyme disease strain was reflected in its
      cell-type-specific binding. Strains that recognized predominantly heparan sulfate
      bound efficiently to both C6 glioma cells and EA-Hy926 cells, whereas strains
      that recognized predominantly dermatan sulfate bound well only to the glial
      cells. The effect of lyase treatment of these cells on bacterial binding was
      consistent with the model that cell-type-specific binding was a reflection of the
      GAG-binding preference. We conclude that the GAG-binding preference varies with
      the strain of Lyme disease spirochete and that this variation influences cell
      type-specific binding in vitro.

PMID- 10085014
TI  - Identification and characterization of the cps locus of Streptococcus suis
      serotype 2: the capsule protects against phagocytosis and is an important
      virulence factor.
AB  - To study the role of the capsule of Streptococcus suis serotype 2 in virulence,
      we generated two isogenic mutants disturbed in capsule production. For that
      purpose, we first cloned and characterized a major part of the capsular
      polysaccharide biosynthesis (cps) locus of S. suis serotype 2. Based on the
      established sequence, 14 open reading frames (ORFs), designated Orf2Z, Orf2Y,
      Orf2X, and Cps2A to Cps2K, were identified. Twelve ORFs belonged to a single
      transcriptional unit. The gene products of 11 of these ORFs showed similarity to
      proteins involved in polysaccharide biosynthesis of other gram-positive
      microorganisms. Nonencapsulated isogenic mutants were generated in the cps2B and
      cps2EF genes by insertional mutagenesis. In contrast to the wild-type S. suis
      serotype 2 strain, the nonencapsulated strains were highly sensitive to ingestion
      by porcine alveolar lung macrophages in vitro. More importantly, the
      nonencapsulated mutant strains were completely avirulent in young germfree pigs
      after intranasal inoculation. These observations indicate that the capsule of S.
      suis serotype 2 plays an essential role in the pathogenesis of S. suis serotype 2
      infections.

PMID- 10085015
TI  - A novel urease-negative Helicobacter species associated with colitis and
      typhlitis in IL-10-deficient mice.
AB  - A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated
      from the intestines of IL-10 (interleukin-10)-deficient (IL-10(-/-)) mice with
      inflammatory bowel disease. The organism was microaerobic, grew at 37 and 42
      degrees C, and was oxidase and catalase positive but urease negative. On the
      basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria,
      the organism is classified as a novel helicobacter. Cesarean section-rederived IL
      10(-/-) mice without helicobacter infection did not have histological evidence of
      intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and
      A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter
      sp. developed variable degrees of inflammation in the lower intestine, and in
      immunocompetent mice, the experimental infection was accompanied by a
      corresponding elevated immunoglobulin G antibody response to the novel
      Helicobacter sp. antigen. These data support other recent studies which
      demonstrate that multiple Helicobacter spp. in both naturally and experimentally
      infected mice can induce inflammatory bowel disease. The mouse model of
      helicobacter-associated intestinal inflammation should prove valuable in
      understanding how specific microbial antigens influence a complex disease
      process.

PMID- 10085016
TI  - Interleukin-12 production is required for chlamydial antigen-pulsed dendritic
      cells to induce protection against live Chlamydia trachomatis infection.
AB  - Immunization with dendritic cells pulsed ex vivo with antigens has been
      successfully used to elicit primary antigen-specific immune responses. We report
      that mouse bone marrow-derived dendritic cells pulsed with inactivated chlamydial
      organisms induced strong protection against live chlamydial infection in a mouse
      lung infection model. Either the dendritic cells or chlamydial organisms alone or
      macrophages similarly pulsed with chlamydial organisms failed to induce any
      significant protection. These observations suggest that dendritic cells can
      efficiently process and present chlamydial antigens to naive T cells in vivo.
      Mice immunized with the chlamydia-pulsed dendritic cells preferentially developed
      a Th1 cell-dominant response while mice immunized with the other immunogens did
      not, suggesting a correlation between a Th1 cell-dominant response and protection
      against chlamydial infection. We further found that dendritic cells produced a
      large amount of interleukin 12 (IL-12) upon ex vivo pulsing with inactivated
      chlamydial organisms, which may allow the dendritic cells to direct a Th1 cell
      dominant response. Dendritic cells from mice deficient in the IL-12 p40 gene
      failed to produce IL-12 after a similar ex vivo pulse with chlamydial organisms,
      and more importantly, immunization with these dendritic cells failed to induce a
      Th1 cell-dominant response and did not induce strong protection against
      chlamydial infection. Thus, the ability of dendritic cells to efficiently process
      and present chlamydial antigens and to produce IL-12 upon chlamydial-organism
      stimulation are both required for the induction of protection against chlamydial
      infection. This information may be useful for the further design of effective
      chlamydial vaccines.

PMID- 10085017
TI  - Listeria monocytogenes phospholipase C-dependent calcium signaling modulates
      bacterial entry into J774 macrophage-like cells.
AB  - Listeria monocytogenes secretes several proteins that have been shown to
      contribute to virulence. Among these is listeriolysin O (LLO), a pore-forming
      hemolysin that is absolutely required for virulence. Two other virulence factors
      are phospholipases: a phosphatidylinositol-specific phospholipase C (PI-PLC
      [plcA]) and a broad-range PLC (plcB). Although mutations in plcA or plcB resulted
      in small increases in mouse 50% lethal dose (LD50), deletions in both genes
      resulted in a 500-fold increase in LD50. We have examined the role of these
      secreted proteins in host intracellular signaling in the J774 macrophage-like
      cell line. Measurements of cytosolic free calcium ([Ca2+]i) have revealed a rapid
      spike upon exposure of these cells to wild-type L. monocytogenes. This is
      followed by a second peak at 5 min and a third prolonged peak with a maximal
      [Ca2+]i of 800 to 1,000 nM. The pattern of calcium changes was greatly altered by
      deletion of any of the three virulence factors. An LLO mutant produced none of
      these elevations in [Ca2+]i; however, a transient elevation was observed whenever
      these bacteria entered the cell. A PI-PLC mutant produced a diminished single
      elevation in [Ca2+]i at 15 to 30 min. A broad-range PLC mutant produced only the
      first calcium spike. Studies with inhibitors suggested that the first elevation
      arises from influx of calcium from the extracellular medium through plasma
      membrane channels and that the second and third elevations come from release of
      Ca2+ from intracellular stores. We observed that internalization of wild-type
      bacteria and the broad-range PLC mutant was delayed for 5 to 10 min, but the LLO
      and PI-PLC mutants were internalized rapidly upon infection. Inhibitors that
      affected calcium signaling changed the kinetics of association of wild-type
      bacteria with J774 cells, the kinetics of entry, and the efficiency of escape
      from the primary phagosome.

PMID- 10085018
TI  - Extracellular cysteine protease produced by Streptococcus pyogenes participates
      in the pathogenesis of invasive skin infection and dissemination in mice.
AB  - The role of an extracellular cysteine protease encoded by the speB gene in group
      A Streptococcus (GAS) skin infection was studied with a mouse model. Mice were
      injected subcutaneously with a wild-type GAS serotype M3 strain or a cysteine
      protease-inactivated isogenic derivative grown to stationary phase. The mortality
      rate of mice injected with the M3 speB mutant strain was significantly decreased
      (P < 0.0008) compared to that of animals injected with the wild-type parental
      organism. The abscesses formed in animals infected with the cysteine protease
      mutant strain were significantly smaller (P < 0.0001) than those caused by the
      wild-type organism and slowly regressed over 3 to 4 weeks. In striking contrast,
      infection with the wild-type GAS isolate generated necrotic lesions, and in some
      animals the GAS disseminated widely from the injection site and produced
      extensive cutaneous damage. All of these animals developed bacteremia and died.
      GAS dissemination was accompanied by severe tissue and blood vessel necrosis.
      Cysteine protease expression in the infected tissue was identified by immunogold
      electron microscopy. These data demonstrate that cysteine protease expression
      contributes to soft tissue pathology, including necrosis, and is required for
      efficient systemic dissemination of the organism from the initial site of skin
      inoculation.

PMID- 10085019
TI  - Rapid local expression of interleukin-12, tumor necrosis factor alpha, and gamma
      interferon after cutaneous Francisella tularensis infection in tularemia-immune
      mice.
AB  - Francisella tularensis LVS is an effective live vaccine strain used for cutaneous
      vaccination against tularemia in man. In mice, injection of LVS causes invasive
      disease and subsequent development of immunity that is characterized by effective
      control of otherwise lethal doses of the organism. In the present investigation,
      it is shown that LVS-immune mice controlled an intradermal infection much more
      effectively than did naive mice; bacterial counts in skin samples were 1.5 to 2.0
      log10 lower 24 h after injection and 6 log10 lower 72 h after injection in immune
      mice. Moreover, in contrast to naive mice, no bacteria were demonstrated in
      samples from livers and spleens of immune mice. By immunohistochemistry, skin
      samples from immune mice showed an intense staining for interleukin-12 (IL-12)
      and a moderate staining for tumor necrosis factor alpha (TNF-alpha) at 24 h
      postinoculation, after which staining for both cytokines faded. In naive mice,
      the staining for IL-12 was weak at all time points and no staining for TNF-alpha
      was observed. No staining for gamma interferon (IFN-gamma) was observed in any
      group before 72 h. At that time point, skin samples from immune mice showed
      moderate staining and skin samples from naive mice showed weak staining. Reverse
      transcriptase PCR showed an induction of mRNA of the three cytokines in the skin
      within the first day after injection. A quantitative analysis demonstrated higher
      IFN-gamma and TNF-alpha mRNA levels in immune mice at 24 h postinoculation. In
      conclusion, immunization with F. tularensis LVS conferred a capability to respond
      to cutaneous reinfection, with rapid local expression of IL-12, TNF-alpha, and
      IFN-gamma, and this expression was paralleled by containment and mitigation of
      the infection. The cytokine response may be part of a local barrier function of
      the skin, important to host protection against tularemia.

PMID- 10085020
TI  - Human embryonic gastric xenografts in nude mice: a new model of Helicobacter
      pylori infection.
AB  - In vitro or animal models have been used to investigate the pathogenesis of
      Helicobacter pylori infection. However, extrapolation to humans of results
      obtained with these heterologous models remains difficult. We have developed a
      new model for the study of H. pylori infection that uses human entire embryonic
      stomachs engrafted in nude mice. At 80 days after implantation, 22 of these
      xenografts, which exhibited a mature gastric epithelium, were inoculated with
      10(7) to 10(8) CFU of either H. pylori LB1, a freshly isolated H. pylori strain
      (n = 12), or H. pylori ATCC 49503 (n = 10). After 12-week examination, H. pylori
      LB1 persistently colonized the antrum of all inoculated grafts, as assessed by
      culture (mucus and mucosa), immunohistochemistry (mucosa), and a rapid urease
      test (mucus). H. pylori ATCC 49503, either before or after in vivo passage,
      permitted only a transient 2-week colonization in one of the five inoculated
      grafts in both groups. Colonization was always associated with an increase of
      gastric juice pH. A mild neutrophil infiltration of the gastric mucosa was noted
      solely in infected grafts. Transmission electron microscopy showed adherence of
      H. pylori organisms to epithelial cell surface. In six animals, intracytoplasmic
      location of this bacterium was observed in the antrum or the fundus. These
      results allow us to propose this model as a new ex vivo model for the study of
      specific H. pylori-gastric cell interactions.

PMID- 10085021
TI  - Anion-coordinating residues at binding site 1 are essential for the biological
      activity of the diphtheria toxin repressor.
AB  - The homodimeric diphtheria toxin repressor (DtxR) uses Fe2+ as a corepressor,
      binds to iron-regulated promoters, and negatively regulates the syntheses of
      diphtheria toxin, corynebacterial siderophore, and several other Corynebacterium
      diphtheriae products. The crystal structure of DtxR shows that the second domain
      of each monomer has two binding sites for Fe2+ or certain other divalent metal
      ions. In addition, site 1 binds a sulfate or phosphate anion, suggesting that
      phosphate may function intracellularly as a co-corepressor. The effects of
      alanine substitutions for selected residues in sites 1 and 2 were determined by
      measuring the beta-galactosidase activities of a tox operator/promoter-lacZ
      reporter construct in Escherichia coli strains expressing each DtxR variant. Our
      studies demonstrated that single alanine substitutions for the anion-binding
      residues in site 1 (R80A, S126A, or N130A) caused severely decreased DtxR
      activity, similar to the effects of alanine substitutions for metal-binding
      residues in site 2 (C102A, E105A, or H106A) and greater than the effects of
      alanine substitutions for metal-binding residues in site 1 (H79A, E83A, or H98A)
      reported previously by other investigators. Various combinations of alanine
      substitutions for site 1 and site 2 residues were also analyzed to further
      elucidate the roles of these cation- and anion-binding ligands in DtxR activity.
      Furthermore, the interaction between residue E20 in the DNA binding domain and
      R80 in anion/cation binding site 1 was analyzed, and the E20A variant of DtxR was
      shown to have a phenotype indistinguishable from that of the R80A variant. Our
      data demonstrated for the first time that the anion-binding residues R80, S126,
      and N130 at site 1 are essential for DtxR activity. The data also showed that the
      interaction of E20 in domain 1 with R80 in domain 2, first revealed by X-ray
      crystallography in apo-DtxR and holo-DtxR, is a structural feature of DtxR that
      is important for its repressor activity.

PMID- 10085022
TI  - Cryptococcus neoformans differential gene expression detected in vitro and in
      vivo with green fluorescent protein.
AB  - Synthetic green fluorescent protein (GFP) was used as a reporter to detect
      differential gene expression in the pathogenic fungus Cryptococcus neoformans.
      Promoters from the C. neoformans actin, GAL7, or mating-type alpha pheromone
      (MFalpha1) genes were fused to GFP, and the resulting reporter genes were used to
      assess gene expression in serotype A C. neoformans. Yeast cells containing an
      integrated pACT::GFP construct demonstrated that the actin promoter was expressed
      during vegetative growth on yeast extract-peptone-dextrose medium. In contrast,
      yeast cells containing the inducible GAL7::GFP or MFalpha1::GFP reporter genes
      expressed significant GFP activity only during growth on galactose medium or V-8
      agar, respectively. These findings demonstrated that the GAL7 and MFalpha1
      promoters from a serotype D C. neoformans strain function when introduced into a
      serotype A strain. Because the MFalpha1 promoter is induced by nutrient
      deprivation and the MATalpha locus containing the MFalpha1 gene has been linked
      with virulence, yeast cells containing the pMFalpha1::GFP reporter gene were
      analyzed for GFP expression in the central nervous system (CNS) of
      immunosuppressed rabbits. In fact, significant GFP expression from the
      MFalpha1::GFP reporter gene was detected after the first week of a CNS infection.
      These findings suggest that there are temporal, host-specific cues that regulate
      gene expression during infection and that the MFalpha1 gene is induced during the
      proliferative stage of a CNS infection. In conclusion, GFP can be used as an
      effective and sensitive reporter to monitor specific C. neoformans gene
      expression in vitro, and GFP reporter constructs can be used as an approach to
      identify a novel gene(s) or to characterize known genes whose expression is
      regulated during infection.

PMID- 10085023
TI  - Antibodies reactive with the N-terminal domain of Plasmodium falciparum serine
      repeat antigen inhibit cell proliferation by agglutinating merozoites and
      schizonts.
AB  - The serine repeat antigen (SERA) is a vaccine candidate antigen of Plasmodium
      falciparum. Immunization of mice with Escherichia coli-produced recombinant
      protein of the SERA N-terminal domain (SE47') induced an antiserum that was
      inhibitory to parasite growth in vitro. Affinity-purified mouse antibodies
      specific to the recombinant protein inhibited parasite growth between the
      schizont and ring stages but not between the ring and schizont stages. When
      Percoll-purified schizonts were cultured with the affinity-purified SE47'
      specific antibodies, schizonts and merozoites were agglutinated. Indirect
      immunofluorescence assays with unfixed parasite cells showed that SE47'-specific
      immunoglobulin G (IgG) bound to SERA molecules on rupturing schizonts and
      merozoites but the IgG did not react with the schizont-infected erythrocytes
      (RBC). Furthermore, double-fluorescence staining against SE47'-specific IgG and
      anti-human RBC membrane IgG showed that the RBC membrane disappeared from SE47'
      specific-IgG-bound schizonts after cultivation. These observations suggest that
      the SE47'-specific antibodies inhibit parasite growth by cross-linking SERA
      molecules that are associated with merozoites in rupturing schizonts with partly
      broken RBC and parasitophorous vacuole membranes, blocking merozoite release.

PMID- 10085024
TI  - Severe impairment in early host defense against Candida albicans in mice
      deficient in myeloperoxidase.
AB  - Myeloperoxidase (MPO) catalyzes the reaction of hydrogen peroxide with chloride
      ion to produce hypochlorous acid (HOCl), which is used for microbial killing by
      phagocytic cells. Despite the important role of MPO in host defense, however, MPO
      deficiency is relatively common in humans, and most of these individuals are in
      good health. To define the in vivo role of MPO, we have generated by gene
      targeting mice having no MPO activity in their neutrophils and monocytes. The
      mice without MPO developed normally, were fertile, and showed normal clearance of
      intraperitoneal Staphylococcus aureus. However, they showed increased
      susceptibility to pneumonia and death following intratracheal infection with
      Candida albicans. Furthermore, the lack of MPO significantly enhanced the
      dissemination of intraperitoneally injected C. albicans into various organs
      during the first 7 days. Thus, MPO is important for early host defense against
      fungal infection, and the inability to generate HOCl cannot be compensated for by
      other oxygen-dependent systems in vivo in mice. The mutant mice serve as a model
      for studying pulmonary and systemic candidiasis.

PMID- 10085025
TI  - Targeted disruption of fibronectin-integrin interactions in human gingival
      fibroblasts by the RI protease of Porphyromonas gingivalis W50.
AB  - Cell surface integrins mediate interactions between cells and their extracellular
      matrix and are frequently exploited by a range of bacterial pathogens to
      facilitate adherence and/or invasion. In this study we examined the effects of
      Porphyromonas gingivalis proteases on human gingival fibroblast (HGF) integrins
      and their fibronectin matrix. Culture supernatant from the virulent strain W50
      caused considerably greater loss of the beta1 integrin subunit from HGF in vitro
      than did that of the beige-pigmented strain W50/BE1. Prior treatment of the W50
      culture supernatant with the protease inhibitor Nalpha-p-tosyl-L-lysine
      chloromethyl ketone (TLCK) blocked its effects on cultured cells, indicating that
      this process is proteolytically mediated. Purified arginine-specific proteases
      from P. gingivalis W50 were able to mimic the effects of the whole-culture
      supernatant on loss of beta1 integrin expression. However purified RI, an
      alpha/beta heterodimer in which the catalytic chain is associated with an adhesin
      chain, was 12 times more active than RIA, the catalytic monomer, in causing loss
      of the alpha5beta1 integrin (fibronectin receptor) from HGF. No effect was
      observed on the alphaVbeta3 integrin (vitronectin receptor). The sites of action
      of RI and RIA were investigated in cells exposed to proteases pretreated with
      TLCK to inactivate the catalytic component. Use of both monoclonal antibody 1A1,
      which recognizes only the adhesin chain of RI, and a rabbit antibody against P.
      gingivalis whole cells indicated localization of RI on the fibroblasts in a
      clear, linear pattern typical of that seen with fibronectin and alpha5beta1
      integrin. Exact colocalization of RI with fibronectin and its alpha5beta1
      receptor was confirmed by double labeling and multiple-exposure photomicroscopy.
      In contrast, RIA bound to fibroblasts in a weak, patchy manner, showing only fine
      linear or granular staining. It is concluded that the adhesin component of RI
      targets the P. gingivalis arginine-protease to sites of fibronectin deposition on
      HGF, contributing to the rapid loss of both fibronectin and its main alpha5beta1
      integrin receptor. Given the importance of integrin-ligand interactions in
      fibroblast function, their targeted disruption by RI may represent a novel
      mechanism of damage in periodontal disease.

PMID- 10085026
TI  - Examination of Listeria monocytogenes intracellular gene expression by using the
      green fluorescent protein of Aequorea victoria.
AB  - The ActA protein of Listeria monocytogenes is an essential virulence factor and
      is required for intracellular bacterial motility and cell-to-cell spread. plcB,
      cotranscribed with actA, encodes a broad-specificity phospholipase C that
      contributes to lysis of host cell vacuoles and cell-to-cell spread. Construction
      of a transcriptional fusion between actA-plcB and the green fluorescent protein
      gene of Aequorea victoria has facilitated the detailed examination of patterns of
      actA/plcB expression within infected tissue culture cells. actA/plcB expression
      began approximately 30 min postinfection and was dependent upon entry of L.
      monocytogenes into the host cytosol. L. monocytogenes Deltahly mutants, which are
      unable to escape from host cell vacuoles, did not express actA/plcB at detectable
      levels within infected tissue culture cells; however, complementation of the hly
      defect allowed entry of the bacteria into the host cytoplasm and subsequent
      actA/plcB expression. These results emphasize the ability of L. monocytogenes to
      sense the different host cell compartment environments encountered during the
      course of infection and to regulate virulence gene expression in response.

PMID- 10085027
TI  - Oligomerization of anthrax toxin protective antigen and binding of lethal factor
      during endocytic uptake into mammalian cells.
AB  - The protective antigen (PA) protein of anthrax toxin binds to a cellular receptor
      and is cleaved by cell surface furin to produce a 63-kDa fragment (PA63). The
      receptor-bound PA63 oligomerizes to a heptamer and acts to translocate the
      catalytic moieties of the toxin, lethal factor (LF) and edema factor (EF), from
      endosomes to the cytosol. In this report, we used nondenaturing gel
      electrophoresis to show that each PA63 subunit in the heptamer can bind one LF
      molecule. Studies using PA immobilized on a plastic surface showed that monomeric
      PA63 is also able to bind LF. The internalization of PA and LF by cells was
      studied with radiolabeled and biotinylated proteins. Uptake was relatively slow,
      with a half-time of 30 min. The number of moles of LF internalized was nearly
      equal to the number of moles of PA subunit internalized. The essential role of PA
      oligomerization in LF translocation was shown with PA protein cleaved at residues
      313-314. The oligomers formed by these proteins during uptake into cells were not
      as stable when subjected to heat and detergent as were those formed by native PA.
      The results show that the structure of the toxin proteins and the kinetics of
      proteolytic activation, LF binding, and internalization are balanced in a way
      that allows each PA63 subunit to internalize an LF molecule. This set of proteins
      has evolved to achieve highly efficient internalization and membrane
      translocation of the catalytic components, LF and EF.

PMID- 10085028
TI  - Identification of a receptor-binding region within domain 4 of the protective
      antigen component of anthrax toxin.
AB  - Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of
      lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are
      the catalytic components of the toxin, whereas PA is the receptor-binding
      component. To identify residues of PA that are involved in interaction with the
      cellular receptor, two solvent-exposed loops of domain 4 of PA (amino acids [aa]
      679 to 693 and 704 to 723) were mutagenized, and the altered proteins purified
      and tested for toxicity in the presence of LF. In addition to the intended
      substitutions, novel mutations were introduced by errors that occurred during
      PCR. Substitutions within the large loop (aa 704 to 723) had no effect on PA
      activity. A mutated protein, LST-35, with three substitutions in the small loop
      (aa 679 to 693), bound weakly to the receptor and was nontoxic. A mutated
      protein, LST-8, with changes in three separate regions did not bind to receptor
      and was nontoxic. Toxicity was greatly decreased by truncation of the C-terminal
      3 to 5 aa, but not by their substitution with nonnative residues or the extension
      of the terminus with nonnative sequences. Comparison of the 28 mutant proteins
      described here showed that the large loop (aa 704 to 722) is not involved in
      receptor binding, whereas residues in and near the small loop (aa 679 to 693)
      play an important role in receptor interaction. Other regions of domain 4, in
      particular residues at the extreme C terminus, appear to play a role in
      stabilizing a conformation needed for receptor-binding activity.

PMID- 10085029
TI  - Capsular sialic acid limits C5a production on type III group B streptococci.
AB  - The majority of type III group B streptococcus (GBS) human neonatal infections
      are caused by a genetically related subgroup called III-3. We have proposed that
      a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal
      infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory
      molecule, but many III-3 strains do not express C5a-ase. The amount of C5a
      produced in serum following incubation with representative type III strains was
      quantitated in order to better understand the relationship between C5a production
      and C5a-ase expression. C5a production following incubation of bacteria with
      serum depleted of antibody to the bacterial surface was inversely proportional to
      the sialic acid content of the bacterial capsule, with the more heavily
      sialylated III-3 strains generating less C5a than the less-virulent, less
      sialylated III-2 strains. The amount of C5a produced correlated significantly
      with C3 deposition on each bacterial strain. Repletion with type-specific
      antibody caused increased C3b deposition and C5a production through alternative
      pathway activation, but C5a was functionally inactivated by strains that
      expressed C5a-ase. The increased virulence of III-3 strains compared to that of
      III-2 strains results at least partially from the higher sialic acid content of
      III-3 strains, which inhibits both opsonophagocytic killing and C5a production in
      the absence of type-specific antibody. We propose that C5a-ase is not necessary
      for III-3 strains to cause invasive disease because the high sialic acid content
      of III-3 strains inhibits C5a production.

PMID- 10085030
TI  - Risk factors in the pathogenesis of invasive group A streptococcal infections:
      role of protective humoral immunity.
AB  - An impressive change in the epidemiology and severity of invasive group A
      streptococcal infections occurred in the 1980s, and the incidence of
      streptococcal toxic shock syndrome cases continues to rise. The reason for the
      resurgence of severe invasive cases remains a mystery-has there been a change in
      the pathogen or in host protective immunity? To address these questions, we have
      studied 33 patients with invasive infection caused by genotypically
      indistinguishable M1T1 strains of Streptococcus pyogenes who had different
      disease outcomes. Patients were classified as having severe (n = 21) and
      nonsevere (n = 12) invasive infections based on the presence or absence of shock
      and organ failure. Levels of anti-M1 bactericidal antibodies and of anti
      streptococcal superantigen neutralizing antibodies in plasma were significantly
      lower in both groups than in age- and geographically matched healthy controls (P
      < 0.01). Importantly, the levels of these protective antibodies in plasma samples
      from severe and nonsevere invasive cases were not different. Together the data
      suggest that low levels of protective antibodies may contribute to host
      susceptibility to invasive streptococcal infection but do not modulate disease
      outcome. Other immunogenetic factors that regulate superantigen responses may
      influence the severity of systemic manifestations associated with invasive
      streptococcal infection.

PMID- 10085031
TI  - Humoral immunity to commensal oral bacteria in human infants: salivary secretory
      immunoglobulin A antibodies reactive with Streptococcus mitis biovar 1,
      Streptococcus oralis, Streptococcus mutans, and Enterococcus faecalis during the
      first two years of life.
AB  - Secretory immunoglobulin A (SIgA) antibodies reactive with the pioneer oral
      streptococci Streptococcus mitis biovar 1 and Streptococcus oralis, the late oral
      colonizer Streptococcus mutans, and the pioneer enteric bacterium Enterococcus
      faecalis in saliva samples from 10 human infants from birth to age 2 years were
      analyzed. Low levels of salivary SIgA1 and SIgA2 antibodies reactive with whole
      cells of all four species were detected within the first month after birth, even
      though S. mutans and E. faecalis were not recovered from the mouths of the
      infants during the study period. Although there was a fivefold increase in the
      concentration of SIgA between birth and age 2 years, there were no differences
      between the concentrations of SIgA1 and SIgA2 antibodies reactive with the four
      species over this time period. When the concentrations of SIgA1 and SIgA2
      antibodies reactive with all four species were normalized to the concentrations
      of SIgA1 and SIgA2 in saliva, SIgA1 and SIgA2 antibodies reactive with these
      bacteria showed a significant decrease from birth to 2 years of age. Adsorption
      of each infant's saliva with cells of one species produced a dramatic reduction
      of antibodies recognizing the other three species. Sequential adsorption of
      saliva samples removed all SIgA antibody to the bacteria, indicating that the
      SIgA antibodies were directed to antigens shared by all four species. The
      induction by the host of a limited immune response to common antigens that are
      likely not involved in adherence may be among the mechanisms that commensal
      streptococci employ to persist in the oral cavity.

PMID- 10085032
TI  - Role of gamma interferon in cellular immune response against murine
      Encephalitozoon cuniculi infection.
AB  - Microsporidia are obligate intracellular protozoan parasites that cause a wide
      variety of opportunistic infection in patients with AIDS. Because it is able to
      grow in vitro, Encephalitozoon cuniculi is currently the best-studied
      microsporidian. T cells mediate protective immunity against this parasite.
      Splenocytes obtained from infected mice proliferate in vitro in response to
      irradiated parasites. A transient state of hyporesponsiveness to parasite antigen
      and mitogen was observed at day 17 postinfection. This downregulatory response
      could be partially reversed by addition of nitric oxide (NO) antagonist to the
      culture. Mice infected with E. cuniculi secrete significant levels of gamma
      interferon (IFN-gamma). Treatment with antibody to IFN-gamma or interleukin-2 (IL
      12) was able to neutralize the resistance to the parasite. Mutant animals lacking
      the IFN-gamma or IL-12 gene were highly susceptible to infection. However, mice
      unable to secrete NO withstood high doses of parasite challenge, similar to
      normal wild-type animals. These studies describe an IFN-gamma-mediated protection
      against E. cuniculi infection that is independent of NO production.

PMID- 10085033
TI  - Mapping of staphylococcal enterotoxin A functional binding sites and presentation
      by monoclonal antibodies and fusion proteins.
AB  - Staphylococal enterotoxins (SE) bind with high affinity to major
      histocompatibility complex (MHC) class II proteins and stimulate large number of
      T cells via the Vbeta region of the T-cell receptor (TCR). To map the epitopes of
      SE type A (SEA) involved in MHC binding and cell proliferation, 20 specific anti
      SEA monoclonal antibodies (MAbs) and two large glutathione S-transferase fusion
      proteins corresponding to the amino and carboxy termini, respectively, of SEA
      were used. The functionality of these antibodies was tested, by MHC binding
      inhibition, interleukin-2 production, and T-cell proliferation assays. Moreover,
      I studied the ability of the MAbs to present SEA in vitro to human and murine
      cells and their reactivity with the two fusion proteins. This study showed that
      all of the MAbs have a defined effect on one or both immunological properties of
      SEA and were able to present SEA to human and murine cells. However, one MAb
      (4H8) recognized SEA but without any interference with its biological activities.
      When the MAbs were tested to react with the two fusion proteins representing the
      SEA molecule, all of the MAbs were negative except for two. These results
      confirmed the presence of two functionally different binding sites of SEA with
      MHC class II molecules and the importance of the disulfide loop for the mitogenic
      activity of SEA. I further demonstrated that MAbs can present SEA to immune cells
      independent of the site recognized by the antibody and that the integrity of the
      SEA molecule is very important for its functions.

PMID- 10085034
TI  - Effects of interleukin-1 receptor antagonist overexpression on infection by
      Listeria monocytogenes.
AB  - Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring cytokine
      whose only known function is the inhibition of interleukin-1 (IL-1). Using a
      reverse genetic approach in mice, we previously showed that increasing IL-1ra
      gene dosage leads to reduced survival of a primary listerial infection. In this
      study, we characterize further the role of endogenously produced IL-1ra and, by
      inference, IL-1 in murine listeriosis. IL-1ra overexpression inhibits, but does
      not eliminate, primary immune responses, reducing survival and increasing
      bacterial loads in the target organs. We demonstrate that IL-1ra functions in the
      innate immune response to regulate the peak leukocyte levels in the blood, the
      accumulation of leukocytes at sites of infection, and the activation of
      macrophages during a primary infection. Reduced macrophage class II major
      histocompatibility complex expression was observed despite increased gamma
      interferon (IFN-gamma) levels, suggesting that IL-1 activity is essential along
      with IFN-gamma for macrophage activation in vivo. We also show that IL-1ra plays
      a more limited role during secondary listeriosis, blunting the strength of the
      delayed-type hypersensitivity response to listerial antigen while not
      significantly altering cellular immunity to a second infectious challenge. When
      these results are compared to those for other mutant mice, IL-1ra appears to be
      unique among the cytokines studied to date in its regulation of leukocyte
      migration during primary listeriosis.

PMID- 10085035
TI  - Characterization of a novel trypanosome lytic factor from human serum.
AB  - Natural resistance of humans to the cattle pathogen Trypanosoma brucei brucei has
      been attributed to the presence in human serum of nonimmune factors that lyse the
      parasite. Normal human serum contains two trypanosome lytic factors (TLFs). TLF1
      is a 500-kDa lipoprotein, which is reported to contain apolipoprotein A-I (apoA
      I), haptoglobin-related protein (Hpr), hemoglobin, paraoxonase, and apoA-II,
      whereas TLF2 is a larger, poorly characterized particle. We report here a new
      immunoaffinity-based purification procedure for TLF2 and TLF1, as well as further
      characterization of the components of each purified TLF. Immunoaffinity-purified
      TLF1 has a specific activity 10-fold higher than that of TLF1 purified by
      previously described methods. Moreover, we find that TLF1 is a lipoprotein
      particle that contains mainly apoA-I and Hpr, trace amounts of paraoxonase, apoA
      II, and haptoglobin, but no detectable hemoglobin. Characterization of TLF2
      reveals that it is a 1,000-kDa protein complex containing mainly immunoglobulin
      M, apoA-I, and Hpr but less than 1% detectable lipid.

PMID- 10085036
TI  - Effect of temperature on growth, hemagglutination, and protease activity of
      Porphyromonas gingivalis.
AB  - Bacteria persisting in periodontal pockets are exposed to elevated temperatures
      during periods of inflammation. Temperature is an environmental factor that can
      modulate gene expression. Consequently, in the present study we examined the
      effect of temperature on the expression of virulence determinants by the
      periodontopathogen, Porphyromonas gingivalis. P. gingivalis W50 was grown in a
      complex medium under hemin excess at pH 7.0 and at a constant temperature of
      either 37, 39, or 41 degrees C; cultures were monitored for protease and
      hemagglutinin activity. P. gingivalis grew well at all three temperatures. An
      increase in growth temperature from 37 to 39 degrees C resulted in a 65%
      reduction in both total arginine- and lysine-specific activities (P < 0.01). A
      further rise in growth temperature to 41 degrees C led to even greater reductions
      in arginine-specific (82%; P < 0.001) and lysine-specific (73%; P < 0. 01)
      activities. These reductions were also associated with an altered distribution of
      individual arginine-specific enzyme isoforms. At 41 degrees C, there was a
      disproportionate reduction in the level of the heterodimeric RI protease, which
      also contains adhesin domains. The reduction also correlated with a markedly
      diminished hemagglutination activity of cells, especially in those grown at 41
      degrees C, and a reduced immunoreactivity with a monoclonal antibody which
      recognizes gene products involved in hemagglutination. Thus, as the environmental
      temperature increased, P. gingivalis adopted a less aggressive phenotype, while
      retaining cell population levels. The coordinate down-regulation of virulence
      gene expression in response to an environmental cue linked to the intensity of
      the host inflammatory response is consistent with the clinically observed
      cyclical nature of disease progression in periodontal diseases.

PMID- 10085037
TI  - Immune response to Yersinia outer proteins and other Yersinia pestis antigens
      after experimental plague infection in mice.
AB  - There is limited information concerning the nature and extent of the immune
      response to the virulence determinants of Yersinia pestis during the course of
      plague infection. In this study, we evaluated the humoral immune response of mice
      that survived lethal Y. pestis aerosol challenge after antibiotic treatment. Such
      a model may replicate the clinical situation in humans and indicate which
      virulence determinants are expressed in vivo. Immunoglobulin G enzyme-linked
      immunosorbent assay and immunoblotting were performed by using purified,
      recombinant antigens including F1, V antigen, YpkA, YopH, YopM, YopB, YopD, YopN,
      YopE, YopK, plasminogen activator protease (Pla), and pH 6 antigen as well as
      purified lipopolysaccharide. The major antigens recognized by murine convalescent
      sera were F1, V antigen, YopH, YopM, YopD, and Pla. Early treatment with
      antibiotics tended to reduce the immune response and differences between
      antibiotic treatment regimens were noted. These results may indicate that only
      some virulence factors are expressed and/or immunogenic during infection. This
      information may prove useful for selecting potential vaccine candidates and for
      developing improved serologic diagnostic assays.

PMID- 10085038
TI  - CD40 ligation prevents Trypanosoma cruzi infection through interleukin-12
      upregulation.
AB  - Because of the critical role of the CD40-CD40 ligand (CD40L) pathway in the
      induction and effector phases of immune responses, we investigated the effects of
      CD40 ligation on the control of Trypanosoma cruzi infection. First, we observed
      that supernatants of murine spleen cells stimulated by CD40L-transfected 3T3
      fibroblasts (3T3-CD40L transfectants) prevent the infection of mouse peritoneal
      macrophages (MPM) by T. cruzi. This phenomenon depends on de novo production of
      nitric oxide (NO) as it is prevented by the addition of N-nitro-L-arginine methyl
      ester, a NO synthase inhibitor. NO production requires interleukin (IL)-12
      mediated gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha)
      synthesis as demonstrated by inhibition experiments using neutralizing anti-IL
      12, anti-IFN-gamma, and anti-TNF-alpha monoclonal antibodies (MAb). We found that
      an activating anti-CD40 MAb also directly stimulates IFN-gamma-activated MPM to
      produce NO and thereby to control T. cruzi infection. To determine the in vivo
      relevance of these in vitro findings, mice were injected with 3T3-CD40L
      transfectants or 3T3 control fibroblasts at the time of T. cruzi inoculation. We
      observed that in vivo CD40 ligation dramatically reduced both parasitemia and the
      mortality rate of T. cruzi-infected mice. A reduced parasitemia was still
      observed when the injection of 3T3-CD40L transfectants was delayed 8 days
      postinfection. It was abolished by injection of anti-IL-12 MAb. Taken together,
      these data establish that CD40 ligation facilitates the control of T. cruzi
      infection through a cascade involving IL-12, IFN-gamma, and NO.

PMID- 10085039
TI  - Characterization of the gene encoding a 26-kilodalton protein (OMP26) from
      nontypeable Haemophilus influenzae and immune responses to the recombinant
      protein.
AB  - A 26-kDa protein (OMP26) isolated and purified from nontypeable Haemophilus
      influenzae (NTHI) strain 289 has been shown to enhance clearance of infection
      following pulmonary challenge with NTHI in rats. DNA sequence analysis revealed
      that it was 99% identical to a gene encoding a cell envelope protein of the H.
      influenzae Rd strain (TIGR accession no. HI0916). The deduced amino acid sequence
      revealed a hydrophilic polypeptide rich in basic amino acids. Restriction
      fragment length polymorphism analysis suggested that the OMP26 gene was
      relatively conserved among isolates of NTHI. Analysis of the deduced amino acid
      sequence of the OMP26 gene from 20 different isolates showed that similarity with
      NTHI-289 ranged from 96.5% (1 isolate) to 99.5% (14 isolates). Two recombinant
      forms of OMP26, a full length 28-kDa protein (equivalent to preprotein) and a 26
      kDa protein lacking a 23-amino-acid leader peptide (equivalent to processed
      protein), were assessed in immunization studies for the ability to induce an
      immune response that would be as effective as the native protein in enhancing the
      clearance of NTHI following pulmonary challenge in rats. Immunization with the
      recombinant protein that included the leader peptide was more effective in
      enhancing pulmonary clearance, and it induced a better cell-mediated response and
      higher titers of systemic and mucosal antibody. This study has characterized a 26
      kDa protein from NTHI that shows significant potential as a vaccine candidate.

PMID- 10085040
TI  - Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis
      media model.
AB  - Streptococcus pneumoniae is the most frequent microbe causing middle ear
      infection. The pathophysiology of pneumococcal otitis media has been
      characterized by measurement of local inflammatory mediators such as inflammatory
      cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The
      role of cytokines in bacterial infection has been elucidated with animal models,
      and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF
      alpha) are recognized as being important local mediators in acute inflammation.
      We characterized middle ear inflammatory responses in the chinchilla otitis media
      model after injecting a very small number of viable pneumococci into the middle
      ear, similar to the natural course of infection. Middle ear fluid (MEF)
      concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti
      human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the
      earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha
      concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8,
      and TNF-alpha but not IL-1beta concentrations correlated significantly with total
      inflammatory cell numbers in MEF, and all four cytokines correlated significantly
      with MEF neutrophil concentration. Several intercytokine correlations were
      significant. Cytokines, therefore, participate in the early middle ear
      inflammatory response to S. pneumoniae.

PMID- 10085041
TI  - Molecular cloning, characterization, and expression of the M antigen of
      Histoplasma capsulatum.
AB  - The major diagnostic antigens of Histoplasma capsulatum are the H and M antigens,
      pluripotent glycoproteins that elicit both humoral and T-cell-mediated immune
      responses. These antigens may play a role in the pathogenesis of histoplasmosis.
      M antigen is considered immunodominant because antibodies against it are the
      first precipitins to arise in acute histoplasmosis and are commonly present
      during all phases of infection. The biological activity of monomolecular M
      antigen and its ability to elicit a protective immune response to H. capsulatum
      are largely unknown. A molecular approach was used to identify the biological
      nature of M antigen, including its purification from histoplasmin, partial
      digestion with proteinases, and reverse-phase high-performance liquid
      chromatography to separate the released peptides. The amino acid sequences of the
      purified peptides were obtained by Edman degradation, and using degenerate
      oligonucleotide primers for PCR, a 321-bp fragment of the gene encoding the M
      antigen was amplified from genomic H. capsulatum DNA. This fragment was used to
      screen an H. capsulatum genomic DNA library, leading to the isolation, cloning,
      and sequencing of the full-length gene. The M gene consists of 2, 187-bp DNA
      encoding a protein of 80,719 Da, which has significant homology to catalases from
      Aspergillus fumigatus, Aspergillus niger, and Eimericella nidulans. A cDNA was
      generated by reverse transcription-PCR and cloned into the expression vector
      pQE40. The identity of the cloned, expressed protein was confirmed by Western
      blotting. The recombinant fusion protein was immunoreactive with monoclonal
      antibodies raised against M antigen, with polyclonal mouse anti-M antiserum, and
      with a serum sample from a patient with histoplasmosis. The gene encoding the
      major immunodominant M antigen of H. capsulatum is a presumptive catalase, and
      the recombinant protein retains serodiagnostic activity.

PMID- 10085042
TI  - Vaccination with cathepsin L proteinases and with leucine aminopeptidase induces
      high levels of protection against fascioliasis in sheep.
AB  - The potential of different parasite proteinases for use as vaccine candidates
      against fascioliasis in sheep was studied by vaccinating animals with the
      cathepsin L proteinases CL1 and CL2 and with leucine aminopeptidase (LAP)
      purified from adult flukes. In the first trial, sheep were immunized with CL1 or
      CL2 and the mean protection levels obtained were 33 and 34%, respectively.
      Furthermore, a significant reduction in egg output was observed in sheep
      vaccinated either with CL1 (71%) or with CL2 (81%). The second trial was
      performed to determine the protective potential of the two cathepsin L
      proteinases assayed together, as well as in combination with LAP, and of LAP
      alone. The combination of CL1 and CL2 induced higher levels of protection (60%)
      than those produced when these enzymes were administered separately. Those sheep
      that received the cocktail vaccine including CL1, CL2, and LAP were significantly
      protected (78%) against metacercarial challenge, but vaccination with LAP alone
      elicited the highest level of protection (89%). All vaccine preparations induced
      high immunoglobulin G titers which were boosted after the challenge infection,
      but no correlations between antibody titers and worm burdens were found. However,
      the sera of those animals vaccinated with LAP contained LAP-neutralizing
      antibodies. Reduced liver damage, as assessed by the level of the liver enzyme
      gamma-glutamyl transferase, was observed in the groups vaccinated with CL1, CL2,
      and LAP or with LAP alone.

PMID- 10085043
TI  - Vaccination and protection of pigs against pleuropneumonia with a vaccine strain
      of Actinobacillus pleuropneumoniae produced by site-specific mutagenesis of the
      ApxII operon.
AB  - The production of toxin (Apx)-neutralizing antibodies during infection plays a
      major role in the induction of protective immunity to Actinobacillus
      pleuropneumoniae reinfection. In the present study, the gene encoding the ApxII
      activating protein, apxIIC, was insertionally inactivated on the chromosome of a
      serovar 7 strain, HS93. Expression of the structural toxin, ApxIIA, and of the
      two genes required for its secretion, apxIB and apxID, still occurs in this
      strain. The resulting mutant strain, HS93C- Ampr, was found to secrete the
      unactivated toxin. Pigs vaccinated with live HS93C- Ampr via the intranasal route
      were protected against a cross-serovar challenge with a virulent serovar 1 strain
      of A. pleuropneumoniae. This is the first reported vaccine strain of A.
      pleuropneumoniae which can be delivered live to pigs and offers cross-serovar
      protection against porcine pleuropneumonia.

PMID- 10085044
TI  - Genetic control of experimental lyme arthritis in the absence of specific
      immunity.
AB  - Host genetics play an important role in determining resistance or susceptibility
      to experimental Lyme arthritis. While specific immunity appears to regulate
      disease resolution, innate immunity appears to regulate disease severity.
      Intradermal infection with Borrelia burgdorferi yields severe arthritis in C3H/He
      (C3H) mice but only minimal arthritis in BALB/c mice. Intradermal infection of
      immunodeficient C3H SCID mice also results in severe arthritis, but arthritis of
      only moderate severity in BALB/c SCID mice. In the present study, we examined
      immunodeficient recombinase-activating gene-knockout (RAG-1(-/-)) (RAG-) mice
      from resistant C57BL/6 (B6) and DBA/2 (DBA) mouse strains. B. burgdorferi
      infected B6 RAG- and DBA RAG- mice had little or no ankle swelling, a low
      occurrence of inflammatory infiltrates in tibiotarsal joints, and low arthritis
      severity scores in comparison to RAG+ and RAG- BALB/c or C3H mice. Few
      differences in spirochete DNA levels in ankles of resistant and susceptible RAG-
      mice were seen. These data suggest that resistance to arthritis development
      following B. burgdorferi infection is not necessarily dependent on an acquired
      immune response and can occur despite the presence of high spirochete burden.
      Thus, genes expressed outside the specific immune response can be central
      regulators of experimental arthritis.

PMID- 10085045
TI  - Salmonella typhimurium encodes a putative iron transport system within the
      centisome 63 pathogenicity island.
AB  - Upon entry into the host, Salmonella enterica strains are presumed to encounter
      an iron-restricted environment. Consequently, these bacteria have evolved a
      variety of often-redundant high-affinity acquisition systems to obtain iron in
      this restricted environment. We have identified an iron transport system that is
      encoded within the centisome 63 pathogenicity island of Salmonella typhimurium.
      The nucleotide composition of this locus is significantly different from that of
      the rest of this pathogenicity island, suggesting a different ancestry and a
      mosaic structure for this region of the S. typhimurium chromosome. This locus,
      designated sit, consists of four open reading frames which encode polypeptides
      with extensive homology to the yfe ABC iron transport system of Yersinia pestis,
      as well as other ABC transporters. The sitA gene encodes a putative periplasmic
      binding protein, sitB encodes an ATP-binding protein, and sitC and sitD encode
      two putative permeases (integral membrane proteins). This operon is capable of
      complementing the growth defect of the enterobactin-deficient Escherichia coli
      strain SAB11 in iron-restricted minimal medium. Transcription of the sit operon
      is repressed under iron-rich growth conditions in a fur-dependent manner.
      Introduction of a sitBCD deletion into wild-type S. typhimurium resulted in no
      apparent growth defect in either nutrient-rich or minimal medium and no
      measurable virulence phenotype. These results further support the existence of
      redundant iron uptake systems in S. enterica.

PMID- 10085046
TI  - The mxi-Spa type III secretory pathway of Shigella flexneri requires an outer
      membrane lipoprotein, MxiM, for invasin translocation.
AB  - Invasion of epithelial cells by Shigella flexneri is mediated by a set of
      translocated bacterial invasins, the Ipa proteins, and its dedicated type III
      secretion system, called Mxi-Spa. We show here that mxiM, part of the mxi-spa
      locus in the S. flexneri virulence plasmid, encodes an indispensable type III
      secretion apparatus component, required for both Ipa translocation and tissue
      culture cell invasion. We demonstrated that mature MxiM, first identified as a
      putative lipoprotein, is lipidated in vivo. Consistent with features of known
      lipoproteins, MxiM (i) can be labeled with [3H]palmitate and [2-3H]glycerol, (ii)
      is associated with the cell envelope, (iii) is secreted independently of the type
      III pathway, and (iv) requires an intact lipoprotein modification and processing
      site for full activity. The lipidated form of MxiM was detected primarily in the
      outer membrane, where it establishes a peripheral association with the inner
      leaflet. Through analysis of subcellular Ipa distribution in a mxiM null mutant
      background, MxiM was found to be required for the assembly and/or function of
      outer, but not inner, membrane regions of Mxi-Spa. This function probably
      requires interactions with other Mxi-Spa subunits within the periplasmic space.
      We discuss implications of these findings with respect to the function of MxiM
      and the structure of Mxi-Spa as a whole.

PMID- 10085047
TI  - Segmented filamentous bacteria are potent stimuli of a physiologically normal
      state of the murine gut mucosal immune system.
AB  - Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the
      intestinal tracts of many species, including humans. We studied the effect of SFB
      on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice
      with SFB. At various time points during 190 days of colonization, fragment
      cultures of small intestine and Peyer's patches (PP) were analyzed for total
      immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes
      indicating germinal center reactions (GCRs) and the activation of CD4(+) T cells
      in PP were determined by using fluorescence-activated cell sorter analyses. A
      second group of SFB-monoassociated mice was colonized with a gram-negative
      commensal, Morganella morganii, to determine if the mucosal immune system was
      again stimulated and to evaluate the effect of prior colonization with SFB on the
      ability of M. morganii to translocate to the spleen and mesenteric lymph nodes.
      We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that
      GCRs only gradually waned over the entire length of colonization, that natural
      IgA production was increased to levels 24 to 63% of that of conventionally reared
      mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of
      total IgA. Also, the proportion of CD4(+), CD45RBlow T cells, indicative of
      activated cells, gradually increased in the PP to the level found in
      conventionally reared mice. Secondary colonization with M. morganii was able to
      stimulate GCRs anew, leading to a specific IgA antibody response. Previous
      stimulation of mucosal immunity by SFB did not prevent the translocation of M.
      morganii in the double-colonized mice. Our findings generally indicate that SFB
      are one of the single most potent microbial stimuli of the gut mucosal immune
      system.

PMID- 10085048
TI  - Adaptive immune response to Shigella flexneri 2a cydC in immunocompetent mice and
      mice lacking immunoglobulin A.
AB  - Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared
      from the lungs of intranasally inoculated mice and was Sereny negative, yet it
      induced 93% protection against challenge with wild-type S. flexneri. Mice that
      lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be
      required for adaptive immunity in this model system.

PMID- 10085049
TI  - Biological properties of structurally related alpha-helical cationic
      antimicrobial peptides.
AB  - A series of alpha-helical cationic antimicrobial peptide variants with small
      amino acid changes was designed. Alterations in the charge, hydrophobicity, or
      length of the variant peptides did not improve the antimicrobial activity, and
      there was no statistically significant correlation between any of these factors
      and the MIC for Pseudomonas aeruginosa, Escherichia coli, or Salmonella
      typhimurium. Individual peptides demonstrated synergy with conventional
      antibiotics against antibiotic-resistant strains of P. aeruginosa. The peptides
      varied considerably in the ability to bind E. coli O111:B4 lipopolysaccharide
      (LPS), and this correlated significantly with their antimicrobial activity and
      ability to block LPS-stimulated tumor necrosis factor and interleukin-6
      production. In general, the peptides studied here demonstrated a broad range of
      activities, including antimicrobial, antiendotoxin, and enhancer activities.

PMID- 10085050
TI  - Vaccinated mice remain more susceptible to Mycobacterium tuberculosis infection
      initiated via the respiratory route than via the intravenous route.
AB  - Mice given Mycobacterium tuberculosis bacilli via the respiratory route succumbed
      much sooner to infection than mice given 1,000 times more bacilli via the
      intravenous route. Vaccination provided increased protection to an M.
      tuberculosis challenge infection; however, mice infected via the respiratory
      route remained much more susceptible.

PMID- 10085051
TI  - Transformation and expression of a cloned fimA gene in Porphyromonas gingivalis.
AB  - The Porphyromonas gingivalis fimbria is an important virulence factor involved in
      the adherence and colonization of the organism in the oral cavity. In this study,
      we transformed this organism with a gene, fimA381, encoding the fimbrial subunit
      of P. gingivalis 381 (fimbrillin) by using the host-vector system that we
      developed previously and examined expression of the cloned fimA381 gene. The
      recombinant plasmid pYHF2 was constructed by ligating a fragment containing the
      fimA381 gene into the plasmid vector pYH420 and transformed into the restriction
      deficient P. gingivalis host YH522. pYHF2 was autonomously maintained in YH522
      cells, and the fimbrillin polypeptide (recombinant fimbrillin) was fully
      expressed. The molecular mass of the recombinant fimbrillin was evaluated by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 41 kDa, which was
      identical to that of the native fimbrillin of strain 381. The amino acid
      sequences of the 20 amino-terminal residues of the recombinant fimbrillin and the
      native fimbrillin of the strain 381 were identical. In addition, characteristic
      long and thin fimbrial structures (recombinant fimbriae) that were
      distinguishable from the host's native fimbriae when examined by immunogold
      electron microscopy were observed around the cell surface of the transformants
      containing the fimA381 gene. These results suggested that transformation of fimA
      gene from a different strain of P. gingivalis followed by accumulation of the
      mature fimbrial subunit protein was sufficient for production of fimbrial
      structures that were observable by electron microscopy.

PMID- 10085052
TI  - Alkaline conditions accelerate polymorphonuclear leukocyte apoptosis in vitro.
AB  - Apoptosis was monitored in polymorphonuclear leukocytes (PMNs) cultured under
      mildly acidic, neutral, and alkaline conditions. Within 3 h, 9.0% of the PMNs
      underwent apoptosis at pH 6.7, as did 12% at pH 7.2, 38% at pH 7.7, and 60% at pH
      8.2. Inhibitors of serine proteases, caspase-1, or caspase-3 significantly
      inhibited PMN apoptosis at pH 8.2, suggesting an involvement by these enzymes.

PMID- 10085053
TI  - Characterization of an immunogenic glycocalyx on the surfaces of Cryptosporidium
      parvum oocysts and sporozoites.
AB  - Ruthenium red staining of Cryptosporidium parvum oocysts revealed the presence of
      a carbohydrate matrix on their outer bilayers that is characteristic of a
      glycocalyx. Surface labeling of intact oocysts identified material of high
      molecular weight (>10(6)) that reacted positively with sera from cryptosporidium
      infected patients and with immunoglobulin A monoclonal antibodies.

PMID- 10085054
TI  - Clonal expansion of antigen-specific CD4 T cells following infection with
      Salmonella typhimurium is similar in susceptible (Itys) and resistant (Ityr)
      BALB/c mice.
AB  - The results show that CD4 T cells specific for a recombinant antigen expressed in
      Salmonella typhimurium proliferate normally in mice that express the susceptible
      form of the Ity gene at early times after infection but do not retain the
      capacity to produce gamma interferon later in the infection.

PMID- 10085055
TI  - Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera
      vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed
      in Panama.
AB  - To provide optimum protection against classical and El Tor biotypes of Vibrio
      cholerae O1, a single-dose, oral cholera vaccine was developed by combining two
      live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El
      Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber
      contained lyophilized bacteria, and the other contained buffer. A total of 170
      partially-immune American soldiers stationed in Panama received one of the
      following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7)
      CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR
      alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated
      Escherichia coli placebo. Among those who received CVD 111 at the high or low
      dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea,
      defined as three or more liquid stools. None of the 32 volunteers who received
      CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected
      in the stools of 46% of the 103 volunteers who received it. About 65% of all
      persons who received CVD 103-HgR either alone or in combination had a fourfold
      rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were
      comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were
      about twice as high in persons who received CVD 111 as in those who received CVD
      103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall
      seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting
      that the combination of an El Tor and a classical cholera strain is desirable.
      While CVD 111 was previously found to be well tolerated in semiimmune Peruvians,
      the adverse effects observed in this study indicate that this strain requires
      further attenuation before it can be safely used in nonimmune populations.

PMID- 10085056
TI  - Characterization of exochelins of the Mycobacterium bovis type strain and BCG
      substrains.
AB  - Pathogenic mycobacteria must acquire iron in the host in order to multiply and
      cause disease. To do so, they release abundant quantities of siderophores called
      exochelins, which have the capacity to scavenge iron from host iron-binding
      proteins and deliver it to the mycobacteria. In this study, we have characterized
      the exochelins of Mycobacterium bovis, the causative agent of bovine and
      occasionally of human tuberculosis, and the highly attenuated descendant of M.
      bovis, bacillus Calmette-Guerin (BCG), widely used as a vaccine against human
      tuberculosis. The M. bovis type strain, five substrains of M. bovis BCG
      (Copenhagen, Glaxo, Japanese, Pasteur, and Tice), and two strains of virulent
      Mycobacterium tuberculosis all produce the same set of exochelins, although the
      relative amounts of individual exochelins may differ. Among these mycobacteria,
      the total amount of exochelins produced is greatest in M. tuberculosis,
      intermediate in M. bovis, and smallest in M. bovis BCG.

PMID- 10085057
TI  - Biological effects of Pseudomonas aeruginosa type III-secreted proteins on CHO
      cells.
AB  - A strain of Pseudomonas aeruginosa that fails to express known type III-secreted
      effector proteins was constructed as an expression host. Individual effectors
      were expressed in trans, and their biological effects on CHO cells were assessed
      in an acute cellular infection model. Intoxication with ExoS, ExoT, or ExoY
      resulted in alterations in cell morphology. As shown in previous genetic studies,
      ExoU expression was linked to acute cytotoxicity.

PMID- 10085058
TI  - beta1-chain integrins are not essential for intimin-mediated host cell attachment
      and enteropathogenic Escherichia coli-induced actin condensation.
AB  - Intimin is a bacterial outer membrane protein required for intimate attachment of
      enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) to
      mammalian cells. beta1-chain integrins have been proposed as candidate receptors
      for intimin. We found that binding of mammalian cells to immobilized intimin was
      not detectable unless mammalian cells were preinfected with EPEC or EHEC. beta1
      chain integrin antagonists or inactivation of the gene encoding the beta1-chain
      did not affect binding of preinfected mammalian cells to intimin or the actin
      condensation associated with the attachment of EPEC. The results indicate that
      beta1-chain integrins are not essential for intimin-mediated cell attachment or
      EPEC-mediated actin polymerization.

PMID- 10085059
TI  - A thematic series on kinases and phosphatases that regulate lipid signaling.

PMID- 10085060
TI  - The role of phosphoinositide 3-kinase lipid products in cell function.

PMID- 10085061
TI  - A model of the transition state in the alkaline phosphatase reaction.
AB  - A high resolution crystal structure of Escherichia coli alkaline phosphatase in
      the presence of vanadate has been refined to 1.9 A resolution. The vanadate ion
      takes on a trigonal bipyramidal geometry and is covalently bound by the active
      site serine nucleophile. A coordinated water molecule occupies the axial position
      opposite the serine nucleophile, whereas the equatorial oxygen atoms of the
      vanadate ion are stabilized by interactions with both Arg-166 and the zinc metal
      ions of the active site. This structural complex supports the in-line
      displacement mechanism of phosphomonoester hydrolysis by alkaline phosphatase and
      provides a model for the proposed transition state in the enzyme-catalyzed
      reaction.

PMID- 10085062
TI  - Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear
      factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta.
AB  - Recent evidence indicates that nuclear factor-kappaB (NF-kappaB), a transcription
      factor critically important for immune and inflammatory responses, is activated
      by a protein kinase cascade. The essential features of this cascade are that a
      mitogen-activated protein kinase kinase kinase (MAP3K) activates an IkappaB
      kinase (IKK) that site-specifically phosphorylates IkappaB. The IkappaB protein,
      which ordinarily sequesters NF-kappaB in the cytoplasm, is subsequently degraded
      by the ubiquitin-proteasome pathway, thereby allowing the nuclear translocation
      of NF-kappaB. Thus far, only two MAP3Ks, NIK and MEKK1, have been identified that
      can activate this pathway. We now show that MEKK2 and MEKK3 can in vivo activate
      IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and,
      relatively modestly, activate an NF-kappaB reporter gene. In addition, dominant
      negative versions of either IKK-alpha or IKK-beta abolish NF-kappaB activation
      induced by MEKK2 or MEKK3, thereby providing evidence that these IKKs mediate the
      NF-kappaB-inducing activities of these MEKKs. In contrast, other MAP3Ks,
      including MEKK4, ASK1, and MLK3, fail to show evidence of activation of the NF
      kappaB pathway. We conclude that a distinct subset of MAP3Ks can activate NF
      kappaB.

PMID- 10085063
TI  - Caspase-9 can be activated without proteolytic processing.
AB  - The recombinant form of the proapoptotic caspase-9 purified following expression
      in Escherichia coli is processed at Asp315, but largely inactive; however, when
      added to cytosolic extracts of human 293 cells it is activated 2000-fold in the
      presence of cytochrome c and dATP. Thus, the characteristic activities of caspase
      9 are context-dependent, and its activation may not recapitulate conventional
      caspase activation mechanisms. To explore this hypothesis we produced recombinant
      forms of procaspase-9 containing mutations that disabled one or both of the
      interdomain processing sites of the zymogen. These mutants were able to activate
      downstream caspases, but only in the presence of cytosolic factors. The mutant
      with both processing sites abolished had 10% of the activity of wild-type, and
      was able to support apoptosis, with equal vigor to wild-type, when transiently
      expressed in 293 cells. Thus caspase-9 has an unusually active zymogen that does
      not require proteolytic processing, but instead is dependent on cytosolic factors
      for expression of its activity.

PMID- 10085064
TI  - DNA demethylase is a processive enzyme.
AB  - DNA methylation patterns are generated during development by a sequence of
      methylation and demethylation events. We have recently demonstrated that mammals
      bear a bona fide demethylase enzyme that removes methyl groups from methylated
      cytosines. A general genome wide demethylation occurs early in development and in
      differentiating cell lines. This manuscript tests the hypothesis that the
      demethylase enzyme is a processive enzyme. Using bisulfite mapping, this report
      demonstrates that demethylase is a processive enzyme and that the rate-limiting
      step in demethylation is the initiation of demethylation. Initiation of
      demethylation is determined by the properties of the sequence. Once initiated,
      demethylation progresses processively. We suggest that these data provide a
      molecular explanation for global hypomethylation.

PMID- 10085065
TI  - Chimeric receptors of the human C3a receptor and C5a receptor (CD88).
AB  - Chimeras were generated between the human anaphylatoxin C3a and C5a receptors
      (C3aR and C5aR, respectively) to define the structural requirements for ligand
      binding and discrimination. Chimeric receptors were generated by systematically
      exchanging between the two receptors four receptor modules (the N terminus,
      transmembrane regions 1 to 4, the second extracellular loop, and transmembrane
      region 5 to the C terminus). The mutants were transiently expressed in HEK-293
      cells (with or without Galpha-16) and analyzed for cell surface expression,
      binding of C3a and C5a, and functional responsiveness (calcium mobilization)
      toward C3a, C5a, and a C3a as well as a C5a analogue peptide. The data indicate
      that in both anaphylatoxin receptors the transmembrane regions and the second
      extracellular loop act as a functional unit that is disrupted by any reciprocal
      exchange. N-terminal substitution confirmed the two-binding site model for the
      human C5aR, in which the receptor N terminus is required for high affinity
      binding of the native ligand but not a C5a analogue peptide. In contrast, the
      human C3a receptor did not require the original N terminus for high affinity
      binding of and activation by C3a, a result that was confirmed by N-terminal
      deletion mutants. This indicates a completely different binding mode of the
      anaphylatoxins to their corresponding receptors. The C5a analogue peptide, but
      not C5a, was an agonist of the C3aR. Replacement of the C3aR N terminus by the
      C5aR sequence, however, lead to the generation of a true hybrid C3a/C5a receptor,
      which bound and functionally responded to both ligands, C3a and C5a.

PMID- 10085066
TI  - c-Abl neutralizes the inhibitory effect of Mdm2 on p53.
AB  - Upon exposure to stress signals, the p53 tumor suppressor protein is stabilized
      and induces growth suppression. p53 activities are efficiently inhibited by the
      Mdm2 oncoprotein through an autoregulatory feedback loop. In addition, Mdm2
      promotes p53 degradation, thereby terminating its growth inhibitory signal.
      Hence, p53 exerts its effects during the interval between p53 activation and the
      subsequent inhibition by Mdm2. Modulation of this interval by regulatory proteins
      may determine the extent and duration of p53 activity. Recent studies have shown
      that the c-Abl protein-tyrosine kinase binds p53 and enhances its transcriptional
      activity. Here we provide an explanation for the cooperation between these
      proteins. We demonstrate that c-Abl increases the expression level of the p53
      protein. The enhanced expression is achieved by inhibiting Mdm2-mediated
      degradation of p53. This provides a likely mechanistic explanation for the
      findings that c-Abl overcomes the inhibitory effects of Mdm2 on p53-mediated
      transcriptional activation and apoptosis. These results suggest that c-Abl
      modulates the time window within which p53 remains active. The ability of c-Abl
      to neutralize the inhibitory effects of Mdm2 on p53 may be important for its
      growth inhibitory function.

PMID- 10085067
TI  - Molecular identification of the apical Ca2+ channel in 1, 25-dihydroxyvitamin D3
      responsive epithelia.
AB  - In mammals, the extracellular calcium concentration is maintained within a narrow
      range despite large variations in daily dietary input and body demand. The small
      intestine and kidney constitute the influx pathways into the extracellular Ca2+
      pool and, therefore, play a primary role in Ca2+ homeostasis. We identified an
      apical Ca2+ influx channel, which is expressed in proximal small intestine, the
      distal part of the nephron and placenta. This novel epithelial Ca2+ channel
      (ECaC) of 730 amino acids contains six putative membrane-spanning domains with an
      additional hydrophobic stretch predicted to be the pore region. ECaC resembles
      the recently cloned capsaicin receptor and the transient receptor potential
      related ion channels with respect to its predicted topology but shares less than
      30% sequence homology with these channels. In kidney, ECaC is abundantly present
      in the apical membrane of Ca2+ transporting cells and colocalizes with 1,25
      dihydroxyvitamin D3-dependent calbindin-D28K. ECaC expression in Xenopus oocytes
      confers Ca2+ influx with properties identical to those observed in distal renal
      cells. Thus, ECaC has the expected properties for being the gatekeeper of 1,25
      dihydroxyvitamin D3-dependent active transepithelial Ca2+ transport.

PMID- 10085068
TI  - Cloning and characterization of a mammalian prenyl protein-specific protease.
AB  - Proteins containing C-terminal "CAAX" sequence motifs undergo three sequential
      post-translational processing steps: modification of the cysteine with either a
      15-carbon farnesyl or 20-carbon geranylgeranyl isoprenyl lipid, proteolysis of
      the C-terminal -AAX tripeptide, and methylation of the carboxyl group of the now
      C-terminal prenylcysteine. A putative prenyl protein protease in yeast,
      designated Rce1p, was recently identified. In this study, a portion of a putative
      human homologue of RCE1 (hRCE1) was identified in a human expressed sequence tag
      data base, and the corresponding cDNA was cloned. Expression of hRCE1 was
      detected in all tissues examined. Both yeast and human RCE1 proteins were
      produced in Sf9 insect cells by infection with a recombinant baculovirus;
      membrane preparations derived from the infected Sf9 cells exhibited a high level
      of prenyl protease activity. Recombinant hRCE1 so produced recognized both
      farnesylated and geranylgeranylated proteins as substrates, including farnesyl-Ki
      Ras, farnesyl-N-Ras, farnesyl-Ha-Ras, and the farnesylated heterotrimeric G
      protein Ggamma1 subunit, as well as geranylgeranyl-Ki-Ras and geranylgeranyl
      Rap1b. The protease activity of hRCE1 activity was specific for prenylated
      proteins, because unprenylated peptides did not compete for enzyme activity.
      hRCE1 activity was also exquisitely sensitive to a prenyl peptide analogue that
      had been previously described as a potent inhibitor of the prenyl protease
      activity in mammalian tissues. These data indicate that both the yeast and the
      human RCE1 gene products are bona fide prenyl protein proteases and suggest that
      they play a major role in the processing of CAAX-type prenylated proteins.

PMID- 10085069
TI  - Disruption of the mouse Rce1 gene results in defective Ras processing and
      mislocalization of Ras within cells.
AB  - Little is known about the enzyme(s) required for the endoproteolytic processing
      of mammalian Ras proteins. We identified a mouse gene (designated Rce1) that
      shares sequence homology with a yeast gene (RCE1) implicated in the proteolytic
      processing of Ras2p. To define the role of Rce1 in mammalian Ras processing, we
      generated and analyzed Rce1-deficient mice. Rce1 deficiency was lethal late in
      embryonic development (after embryonic day 15.5). Multiple lines of evidence
      revealed that Rce1-deficient embryos and cells lacked the ability to
      endoproteolytically process Ras proteins. First, Ras proteins from Rce1-deficient
      cells migrated more slowly on SDS-polyacrylamide gels than Ras proteins from wild
      type embryos and fibroblasts. Second, metabolic labeling of Rce1-deficient cells
      revealed that the Ras proteins were not carboxymethylated. Finally, membranes
      from Rce1-deficient fibroblasts lacked the capacity to proteolytically process
      farnesylated Ha-Ras, N-Ras, and Ki-Ras or geranylgeranylated Ki-Ras. The
      processing of two other prenylated proteins, the farnesylated Ggamma1 subunit of
      transducin and geranylgeranylated Rap1B, was also blocked. The absence of
      endoproteolytic processing and carboxymethylation caused Ras proteins to be
      mislocalized within cells. These studies indicate that Rce1 is responsible for
      the endoproteolytic processing of the Ras proteins in mammals and suggest a broad
      role for this gene in processing other prenylated CAAX proteins.

PMID- 10085070
TI  - Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation
      of cyclic AMP response element-dependent gene transcription.
AB  - The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response
      element (CRE)-dependent gene transcription was compared with that of cAMP
      dependent protein kinases (cAKs). Although both the type Ibeta cGMP-dependent
      protein kinase (cGKIbeta) and the type II cAMP-dependent protein kinase (cAKII)
      phosphorylated the cytoplasmic substrate VASP (vasodilator- and A kinase
      stimulated phosphoprotein) to a similar extent, cyclic nucleotide regulation of
      CRE-dependent transcription was at least 10-fold higher in cAKII-transfected
      cells than in cGKIbeta-transfected cells. Overexpression of each kinase in
      mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme.
      As reported previously, the catalytic (C) subunit of cAKII translocated to the
      nucleus following activation by 8-bromo-cyclic AMP. However, cGKIbeta did not
      translocate to the nucleus upon activation by 8-bromo-cyclic GMP. Replacement of
      an autophosphorylated serine (Ser79) of cGKIbeta with an aspartic acid resulted
      in a mutant kinase with constitutive kinase activity in vitro and in vivo. The
      cGKIbetaS79D mutant localized to the cytoplasm and was only a weak activator of
      CRE-dependent gene transcription. However, an amino-terminal deletion mutant of
      cGKIbeta was found in the nucleus as well as the cytoplasm and was a strong
      activator of CRE-dependent gene transcription. These data suggest that the
      inability of cGKs to translocate to the nucleus is responsible for the
      differential ability of cAKs and cGKs to activate CRE-dependent gene
      transcription and that nuclear redistribution of cGKs is not required for NO/cGMP
      regulation of gene transcription.

PMID- 10085071
TI  - Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to
      defensins, protegrins, and other antimicrobial peptides.
AB  - Positively charged antimicrobial peptides with membrane-damaging activity are
      produced by animals and humans as components of their innate immunity against
      bacterial infections and also by many bacteria to inhibit competing
      microorganisms. Staphylococcus aureus and Staphylococcus xylosus, which tolerate
      high concentrations of several antimicrobial peptides, were mutagenized to
      identify genes responsible for this insensitivity. Several mutants with increased
      sensitivity were obtained, which exhibited an altered structure of teichoic
      acids, major components of the Gram-positive cell wall. The mutant teichoic acids
      lacked D-alanine, as a result of which the cells carried an increased negative
      surface charge. The mutant cells bound fewer anionic, but more positively charged
      proteins. They were sensitive to human defensin HNP1-3, animal-derived
      protegrins, tachyplesins, and magainin II, and to the bacteria-derived peptides
      gallidermin and nisin. The mutated genes shared sequence similarity with the dlt
      genes involved in the transfer of D-alanine into teichoic acids from other Gram
      positive bacteria. Wild-type strains bearing additional copies of the dlt operon
      produced teichoic acids with higher amounts of D-alanine esters, bound cationic
      proteins less effectively and were less sensitive to antimicrobial peptides. We
      propose a role of the D-alanine-esterified teichoic acids which occur in many
      pathogenic bacteria in the protection against human and animal defense systems.

PMID- 10085072
TI  - Surface exposure of the methionine side chains of calmodulin in solution. A
      nitroxide spin label and two-dimensional NMR study.
AB  - Binding of calcium to calmodulin (CaM) causes a conformational change in this
      ubiquitous calcium regulatory protein that allows the activation of many target
      proteins. Met residues make up a large portion of its hydrophobic target binding
      surfaces. In this work, we have studied the surface exposure of the Met residues
      in the apo- and calcium-bound states of CaM in solution. Complexes of calcium-CaM
      with synthetic peptides derived from the CaM-binding domains of myosin light
      chain kinase, constitutive nitric-oxide synthase, and CaM-dependent protein
      kinase I were also studied. The surface exposure was measured by NMR by studying
      the effects of the soluble nitroxide spin label, 4-hydroxyl-2,2,6, 6
      tetramethylpiperidinyl-1-oxy, on the line widths and relaxation rates of the Met
      methyl resonances in samples of biosynthetically 13C-methyl-Met-labeled CaM. The
      Met residues move from an almost completely buried state in apo-CaM to an
      essentially fully exposed state in Ca2+4-CaM. Binding of two Ca2+ to the C
      terminal lobe of CaM causes full exposure of the C-terminal Met residues and a
      partial exposure of the N-terminal Met side chains. Binding of the three target
      peptides blocks the access of the nitroxide surface probe to nearly all Met
      residues, although the mode of binding is distinct for the three peptides
      studied. These data show that calcium binding to CaM controls the surface
      exposure of the Met residues, thereby providing the switch for target protein
      binding.

PMID- 10085073
TI  - Mutants in ABC10beta, a conserved subunit shared by all three yeast RNA
      polymerases, specifically affect RNA polymerase I assembly.
AB  - ABC10beta, a small polypeptide common to the three yeast RNA polymerases, has
      close homology to the N subunit of the archaeal enzyme and is remotely related to
      the smallest subunit of vaccinial RNA polymerase. The eucaryotic, archaeal, and
      viral polypeptides share an invariant motif CX2C. CC that is strictly essential
      for yeast growth, as shown by site-directed mutagenesis, whereas the rest of the
      ABC10beta sequence is fairly tolerant to amino acid replacements. ABC10beta has
      Zn2+ binding properties in vitro, and the CX2C. CC motif may therefore define an
      atypical metal-chelating site. Hybrid subunits that derive most of their amino
      acids from the archaeal subunit are functional in yeast, indicating that the
      archaeal and eucaryotic polypeptides have a largely equivalent role in the
      organization of their respective transcription complexes. However, all eucaryotic
      forms of ABC10beta harbor a HVDLIEK motif that, when mutated or replaced by its
      archaeal counterpart, leads to a polymerase I-specific lethal defect in vivo.
      This is accompanied by a specific lack in the largest subunit of RNA polymerase I
      (A190) in cell-free extracts, showing that the mutant enzyme is not properly
      assembled in vivo.

PMID- 10085074
TI  - Re-design of Rhodobacter sphaeroides dimethyl sulfoxide reductase. Enhancement of
      adenosine N1-oxide reductase activity.
AB  - The periplasmic DMSO reductase from Rhodobacter sphaeroides f. sp. denitrificans
      has been expressed in Escherichia coli BL21(DE3) cells in its mature form and
      with the R. sphaeroides or E. coli N-terminal signal sequence. Whereas the R.
      sphaeroides signal sequence prevents formation of active enzyme, addition of a 6x
      His-tag at the N terminus of the mature peptide maximizes production of active
      enzyme and allows for affinity purification. The recombinant protein contains 1.7
      1.9 guanines and greater than 0.7 molybdenum atoms per molecule and has a DMSO
      reductase activity of 3.4-3.7 units/nmol molybdenum, compared with 3.7 units/nmol
      molybdenum for enzyme purified from R. sphaeroides. The recombinant enzyme
      differs from the native enzyme in its color and spectrum but is indistinguishable
      from the native protein after redox cycling with reduced methyl viologen and
      Me2SO. Substitution of Cys for the molybdenum-ligating Ser-147 produced a protein
      with DMSO reductase activity of 1.4-1.5 units/nmol molybdenum. The mutant protein
      differs from wild type in its color and absorption spectrum in both the oxidized
      and reduced states. This substitution leads to losses of 61-99% of activity
      toward five substrates, but the adenosine N1-oxide reductase activity increases
      by over 400%.

PMID- 10085075
TI  - c-myc intron element-binding proteins are required for 1, 25-dihydroxyvitamin D3
      regulation of c-myc during HL-60 cell differentiation and the involvement of
      HOXB4.
AB  - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) suppresses c-myc expression during
      differentiation of HL-60 cells along the monocytic pathway by blocking
      transcriptional elongation at the first exon/intron border of the c-myc gene. In
      the present study, the physiological relevance of three putative regulatory
      protein binding sites found within a 280-base pair region in intron 1 of the c
      myc gene was explored. HL-60 promyelocytic leukemia cells were transiently
      transfected with three different c-myc promoter constructs cloned upstream of a
      chloramphenicol acetyltransferase (CAT) reporter gene. With the wild-type c-myc
      promoter construct (pMPCAT), which contains MIE1, MIE2, and MIE3 binding sites,
      1,25-(OH)2D3 was able to decrease CAT activity by 45.4 +/- 7.9% (mean +/- S.E., n
      = 8). The ability of 1, 25-(OH)2D3 to inhibit CAT activity was significantly
      decreased to 18. 5 +/- 4.3% (59.3% reversal, p < 0.02) when examined with a MIE1
      deletion construct (pMPCAT-MIE1). Moreover, 1,25-(OH)2D3 was completely
      ineffective at suppressing CAT activity in cells transfected with pMPCAT-287, a
      construct without MIE1, MIE2, and MIE3 binding sites (-6.5 +/- 10.9%, p < 0.002).
      MIE1- and MIE2-binding proteins induced by 1,25-(OH)2D3 had similar gel shift
      mobilities, while MIE3-binding proteins migrated differently. Furthermore,
      chelerythrine chloride, a selective protein kinase C (PKC) inhibitor, and a
      PKCbeta antisense oligonucleotide completely blocked the binding of nuclear
      proteins induced by 1,25-(OH)2D3 to MIE1, MIE2, and MIE3. A 1,25-(OH)2D3
      inducible MIE1-binding protein was identified to be HOXB4. HOXB4 levels were
      significantly increased in response to 1,25-(OH)2D3. Taken together, these
      results indicate that HOXB4 is one of the nuclear phosphoproteins involved in c
      myc transcription elongation block during HL-60 cell differentiation by 1,25
      (OH)2D3.

PMID- 10085076
TI  - Identification of D-proline reductase from Clostridium sticklandii as a
      selenoenzyme and indications for a catalytically active pyruvoyl group derived
      from a cysteine residue by cleavage of a proprotein.
AB  - Highly active D-proline reductase was obtained from Clostridium sticklandii by a
      modified purification scheme. The cytoplasmic enzyme had a molecular mass of
      about 870 kDa and was composed of three subunits with molecular masses of 23, 26,
      and 45 kDa. The 23-kDa subunit contained a carbonyl group at its N terminus,
      which could either be labeled with fluorescein thiosemicarbazide or removed by o
      phenylenediamine; thus, N-terminal sequencing became feasible for this subunit. L
      [14C]proline was covalently bound to the 23-kDa subunit if proline racemase and
      NaBH4 were added. Selenocysteine was detected in the 26-kDa subunit, which
      correlated with an observed selenium content of 10.6 g-atoms in D-proline
      reductase. No other non-proteinaceous cofactor was identified in the enzyme. A
      4.8-kilobase pair (kb) EcoRI fragment was isolated and sequenced containing the
      two genes prdA and prdB. prdA coding for a 68-kDa protein was most likely
      translated as a proprotein that was posttranslationally cleaved at a threonine
      cysteine site to give the 45-kDa subunit and most probably a pyruvoyl-containing
      23-kDa subunit. The gene prdB encoded the 26-kDa subunit and contained an in
      frame UGA codon for selenocysteine insertion. prdA and prdB were transcribed
      together on a transcript of 4.5 kb; prdB was additionally transcribed as
      indicated by a 0.8-kb mRNA species.

PMID- 10085077
TI  - TWEAK induces angiogenesis and proliferation of endothelial cells.
AB  - TWEAK is a recently described member of the Tumor Necrosis Factor (TNF) ligand
      family whose transcripts are present in a wide variety of human tissues
      (Chicheportiche, Y., Bourdon, P. R., Xu, H., Hsu Y. M., Scott, H., Hession, C.,
      Garcia, I., and Browning, J. L. (1997) J. Biol. Chem. 272, 32401-32410). TWEAK is
      a weak inducer of apoptosis in transformed cells when administered with
      interferon-gamma or cycloheximide (Chicheportiche, Y., Bourdon, P. R., Xu, H.,
      Hsu Y. M., Scott, H., Hession, C., Garcia, I., and Browning, J. L. (1997) J.
      Biol. Chem. 272, 32401-32410; Masters, S. A., Sheridan, J. P., Pitti, R. M.,
      Brush, A. G., and Ashkenazi, A. (1998) Curr. Biol. 8, 525-528) and also promotes
      IL-8 secretion in cultured cells. We report here that picomolar concentrations of
      recombinant soluble TWEAK induce proliferation in a variety of normal human
      endothelial cells and in aortic smooth muscle cells and reduce culture
      requirements for serum and growth factors. Blocking antibodies to Vascular
      Endothelial Growth Factor (VEGF) do not significantly inhibit TWEAK-induced
      proliferation, indicating that TWEAK does not function indirectly through up
      regulation of VEGF. Pellets containing TWEAK induce a strong angiogenic response
      when implanted in rat corneas, suggesting a role for TWEAK in vasculature
      formation in vivo.

PMID- 10085078
TI  - Xenopus cytosolic thyroid hormone-binding protein (xCTBP) is aldehyde
      dehydrogenase catalyzing the formation of retinoic acid.
AB  - Amino acid sequencing of an internal peptide fragment derived from purified
      Xenopus cytosolic thyroid hormone-binding protein (xCTBP) demonstrates high
      similarity to the corresponding sequence of mammalian aldehyde dehydrogenase 1
      (ALDH1) (Yamauchi, K., and Tata, J. R. (1994) Eur. J. Biochem. 225, 1105-1112).
      Here we show that xCTBP was co-purified with ALDH and 3,3',5-triiodo-L-thyronine
      (T3) binding activities. By photoaffinity labeling with [125I]T3, a T3-binding
      site in the xCTBP was estimated to reside in amino acid residues 93-114, which is
      distinct from the active site of the enzyme but present in the NAD+ binding
      domain. The amino acid sequences deduced from the two isolated xALDH1 cDNAs
      (xALDH1-I and xALDH1-II) were 94.6% identical to each other and very similar to
      those of mammalian ALDH1 enzymes. The two recombinant xALDH1 proteins exhibit
      both T3 binding activity and ALDH activity converting retinal to retinoic acid
      (RA), which are similar to those of xCTBP. The mRNAs were present abundantly in
      kidney and intestine of adult female Xenopus. Interestingly, their T3 binding
      activities were inhibited by NAD+ and NADH but not by NADP+ and NADPH, whereas
      NAD+ was required for their ALDH activities. Our results demonstrate that xCTBP
      is identical to ALDH1 and suggest that this protein might modulate RA synthesis
      and intracellular level of free T3.

PMID- 10085079
TI  - Isolation and expression of novel human glutamate carboxypeptidases with N
      acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity.
AB  - Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) by N
      acetylated alpha-linked acidic dipeptidase (NAALADase) to release glutamate may
      be important in a number of neurodegenerative disorders in which excitotoxic
      mechanisms are implicated. The gene coding for human prostate-specific membrane
      antigen, a marker of prostatic carcinomas, and its rat homologue glutamate
      carboxypeptidase II have recently been shown to possess such NAALADase activity.
      In contrast, a closely related member of this gene family, rat ileal 100-kDa
      protein, possesses a dipeptidyl peptidase IV activity. Here, we describe the
      cloning of human ileal 100-kDa protein, which we have called a NAALADase- "like"
      (NAALADase L) peptidase based on its sequence similarity to other members of this
      gene family, and its inability to hydrolyze NAAG in transient transfection
      experiments. Furthermore, we describe the cloning of a third novel member of this
      gene family, NAALADase II, which codes for a type II integral membrane protein
      and which we have localized to chromosome 11 by fluorescent in situ hybridization
      analysis. Transient transfection of NAALADase II cDNA confers both NAALADase and
      dipeptidyl peptidase IV activity to COS cells. Expression studies using reverse
      transcription-polymerase chain reaction and Northern blot hybridization show that
      NAALADase II is highly expressed in ovary and testis as well as within discrete
      brain areas.

PMID- 10085080
TI  - Membrane topology of the lactococcal bacteriocin ATP-binding cassette transporter
      protein LcnC. Involvement of LcnC in lactococcin a maturation.
AB  - Many non-lantibiotic bacteriocins of lactic acid bacteria are produced as
      precursors with N-terminal leader peptides different from those present in
      preproteins exported by the general sec-dependent (type II) secretion pathway.
      These bacteriocins utilize a dedicated (type I) secretion system for
      externalization. The secretion apparatus for the lactococcins A, B, and M/N
      (LcnA, B, and M/N) from Lactococcus lactis is composed of the two membrane
      proteins LcnC and LcnD. LcnC belongs to the ATP-binding cassette transporters,
      whereas LcnD is a protein with similarities to other accessory proteins of type I
      secretion systems. This paper shows that the N-terminal part of LcnC is involved
      in the processing of the precursor of LcnA. By making translational fusions of
      LcnC to the reporter proteins beta-galactosidase (LacZ) and alkaline phosphatase
      (PhoA*), it was shown that both the N- and C-terminal parts of LcnC are located
      in the cytoplasm. As the N terminus of LcnC is required for LcnA maturation and
      is localized in the cytoplasm, we conclude that the processing of the bacteriocin
      LcnA to its mature form takes place at the cytosolic side of the cytoplasmic
      membrane.

PMID- 10085081
TI  - Organophosphorylation of acetylcholinesterase in the presence of peripheral site
      ligands. Distinct effects of propidium and fasciculin.
AB  - Structural analysis of acetylcholinesterase (AChE) has revealed two sites of
      ligand interaction in the active site gorge: an acylation site at the base of the
      gorge and a peripheral site at its mouth. A goal of our studies is to understand
      how ligand binding to the peripheral site alters the reactivity of substrates and
      organophosphates at the acylation site. Kinetic rate constants were determined
      for the phosphorylation of AChE by two fluorogenic organophosphates, 7
      [(diethoxyphosphoryl)oxy]-1-methylquinolinium iodide (DEPQ) and 7
      [(methylethoxyphosphonyl)oxy]-4-methylcoumarin (EMPC), by monitoring release of
      the fluorescent leaving group. Rate constants obtained with human erythrocyte
      AChE were in good agreement with those obtained for recombinant human AChE
      produced from a high level Drosophila S2 cell expression system. First-order rate
      constants kOP were 1,600 +/- 300 min-1 for DEPQ and 150 +/- 11 min-1 for EMPC,
      and second-order rate constants kOP/KOP were 193 +/- 13 microM-1 min-1 for DEPQ
      and 0.7-1.0 +/- 0.1 microM-1 min-1 for EMPC. Binding of the small ligand
      propidium to the AChE peripheral site decreased kOP/KOP by factors of 2-20 for
      these organophosphates. Such modest inhibitory effects are consistent with our
      recently proposed steric blockade model (Szegletes, T., Mallender, W. D., and
      Rosenberry, T. L. (1998) Biochemistry 37, 4206-4216). Moreover, the binding of
      propidium resulted in a clear increase in kOP for EMPC, suggesting that molecular
      or electronic strain caused by the proximity of propidium to EMPC in the ternary
      complex may promote phosphorylation. In contrast, the binding of the polypeptide
      neurotoxin fasciculin to the peripheral site of AChE dramatically decreased
      phosphorylation rate constants. Values of kOP/KOP were decreased by factors of
      10(3) to 10(5), and kOP was decreased by factors of 300-4,000. Such pronounced
      inhibition suggested a conformational change in the acylation site induced by
      fasciculin binding. As a note of caution to other investigators, measurements of
      phosphorylation of the fasciculin-AChE complex by AChE inactivation gave
      misleading rate constants because a small fraction of the AChE was resistant to
      inhibition by fasciculin.

PMID- 10085082
TI  - Plasmin converts factor X from coagulation zymogen to fibrinolysis cofactor.
AB  - Known anticoagulant pathways have been shown to exclusively inhibit blood
      coagulation cofactors and enzymes. In the current work, we first investigated the
      possibility of a novel anticoagulant mechanism that functions at the level of
      zymogen inactivation. Utilizing both clotting and chromogenic assays, the
      fibrinolysis protease plasmin was found to irreversibly inhibit the pivotal
      function of factor X (FX) in coagulation. This was due to cleavage at several
      sites, the location of which were altered by association of FX with procoagulant
      phospholipid (proPL). The final products were approximately 28 and approximately
      47 kDa for proPL-bound and unbound FX, respectively, which did not have analogues
      when activated FX (FXa) was cleaved instead. We next investigated whether the FX
      derivatives could interact with the plasmin precursor plasminogen, and we found
      that plasmin exposed a binding site only on proPL-bound FX. The highest apparent
      affinity was for the 28-kDa fragment, which was identified as the light subunit
      disulfide linked to a small fragment of the heavy subunit (Met-296 to
      approximately Lys-330). After cleavage by plasmin, proPL-bound FX furthermore was
      observed to accelerate plasmin generation by tissue plasminogen activator. Thus,
      a feedback mechanism localized by proPL is suggested in which plasmin
      simultaneously inhibits FX clotting function and converts proPL-bound FX into a
      fibrinolysis cofactor. These data also provide the first evidence for an
      anticoagulant mechanism aimed directly at the zymogen FX.

PMID- 10085083
TI  - Activation of serum response factor by RhoA is mediated by the nuclear factor
      kappaB and C/EBP transcription factors.
AB  - The activity of the transcription factor NF-kappaB can be modulated by members of
      the Rho family of small GTPases (Perona, R., Montaner, S., Saniger, L., Sanchez
      Perez, I., Bravo, R., and Lacal, J. C. (1997) Genes Dev. 11, 463-475). Ectopic
      expression of RhoA, Rac1, and Cdc42Hs proteins induces the translocation of NF
      kappaB dimers to the nucleus, triggering the transactivation of the NF-kappaB
      dependent promoter from the human immunodeficiency virus. Here, we demonstrate
      that activation of NF-kappaB by RhoA does not exclusively promote its nuclear
      translocation and binding to the specific kappaB sequences. NF-kappaB is also
      involved in the regulation of the transcriptional activity of the c-fos serum
      response factor (SRF), since the activation of a SRE-dependent promoter by RhoA
      can be efficiently interfered by the double mutant IkappaBalphaS32A/S36A, an
      inhibitor of the NF-kappaB activity. We also present evidence that RelA and p50
      NF-kappaB subunits cooperate with the transcription factor C/EBPbeta in the
      transactivation of the 4 x SRE-CAT reporter. Furthermore, RhoA increases the
      levels of C/EBPbeta protein, facilitating the functional cooperation between NF
      kappaB, C/EBPbeta, and SRF proteins. These results strengthen the pivotal
      importance of the Rho family of small GTPases in signal transduction pathways
      which modulate gene expression and reveal that NF-kappaB and C/EBPbeta
      transcription factors are accessory proteins for the RhoA-linked regulation of
      the activity of the SRF.

PMID- 10085084
TI  - Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA
      containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5
      hydroxycytosine.
AB  - We recently showed that abasic sites, uracil mismatches, nicks, and gaps can trap
      DNA topoisomerase I (top1) when these lesions are introduced in the vicinity of a
      top1 cleavage site (Pourquier, P., Ueng, L.-M., Kohlhagen, G., Mazumder, A.,
      Gupta, M., Kohn, K. W., and Pommier, Y. (1997) J. Biol. Chem. 272, 7792-7796;
      Pourquier, P., Pilon, A. A., Kohlhagen, G., Mazumder, A., Sharma, A., and
      Pommier, Y. (1997) J. Biol. Chem. 26441-26447). In this study, we investigated
      the effects on top1 of an abundant base damage generated by various oxidative
      stresses: 7,8-dihydro-8-oxoguanine (8-oxoG). Using purified eukaryotic top1 and
      oligonucleotides containing the 8-oxoG modification, we found a 3-7-fold increase
      in top1-mediated DNA cleavage when 8-oxoG was present at the +1 or +2 position
      relative to the cleavage site. Another oxidative lesion, 5-hydroxycytosine, also
      enhanced top1 cleavage by 2-fold when incorporated at the +1 position of the
      scissile strand. 8-oxoG at the +1 position enhanced noncovalent top1 DNA binding
      and had no detectable effect on DNA religation or on the incision step. top1
      trapping by 8-oxoG was markedly enhanced when asparagine adjacent to the
      catalytic tyrosine was mutated to histidine, suggesting a direct interaction
      between this residue and the DNA major groove immediately downstream from the
      top1 cleavage site. Altogether, these results demonstrate that oxidative base
      lesions can increase top1 binding to DNA and induce top1 cleavage complexes.

PMID- 10085085
TI  - Activation of the Cdc42-associated tyrosine kinase-2 (ACK-2) by cell adhesion via
      integrin beta1.
AB  - Activated Cdc42-associated kinase-2 (ACK-2) is a non-receptor tyrosine kinase
      that appears to be a highly specific target for the Rho-related GTP-binding
      protein Cdc42. In order to understand better how ACK-2 activity is regulated in
      cells, we have expressed epitope-tagged forms of this tyrosine kinase in COS-7
      and NIH3T3 cells. We find that ACK-2 can be activated by cell adhesion in a Cdc42
      dependent manner. However, unlike the focal adhesion kinase, which also is
      activated by cell adhesion, the activation of ACK-2 is F-actin-independent and
      does not require cell spreading. In addition, overexpression of ACK-2 in COS-7
      cells did not result in the stimulation of extracellular signal-regulated kinase
      activity but rather activated the c-Jun kinase. Both anti-integrin beta1 antibody
      and RGD peptides inhibited the activation of ACK-2 by cell adhesion. In addition,
      ACK-2 was co-immunoprecipitated with integrin beta1. Overall, these findings
      suggest that ACK-2 interacts with integrin complexes and mediates cell adhesion
      signals in a Cdc42-dependent manner.

PMID- 10085086
TI  - Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB
      activation in primary hippocampal neurons.
AB  - Emerging data indicate that tumor necrosis factor (TNF) exerts a neuroprotective
      effect in response to brain injury. Here we examined the mechanism of TNF in
      preventing neuronal death in primary hippocampal neurons. TNF protected neurons
      against hypoxia- or nitric oxide-induced injury, with an increase in the anti
      apoptotic proteins Bcl-2 and Bcl-x as determined by Western blot and reverse
      transcriptase-polymerase chain reaction analysis. Treatment of neurons with an
      antisense oligonucleotide to bcl-2 mRNA or that to bcl-x mRNA blocked the up
      regulation of Bcl-2 or Bcl-x expression, respectively, and partially inhibited
      the neuroprotective effect induced by TNF. Moreover, adenovirus-mediated
      overexpression of Bcl-2 significantly inhibited hypoxia- or nitric oxide-induced
      neuronal death. To examine the possible involvement of a transcription factor,
      NFkappaB, in the regulation of Bcl-2 and Bcl-x expression in TNF-treated neurons,
      an adenoviral vector capable of expressing a mutated form of IkappaB was used to
      infect neurons prior to TNF treatment. Expression of the mutant NFkappaB
      completely inhibited NFkappaB DNA binding activity and inhibited both TNF-induced
      up-regulation of Bcl-2 and Bcl-x expression and neuroprotective effect. These
      findings indicate that induction of Bcl-2 and Bcl-x expression through NFkappaB
      activation is involved in the neuroprotective action of TNF against hypoxia- or
      nitric oxide-induced injury.

PMID- 10085087
TI  - Correlations in palmitoylation and multiple phosphorylation of rat bradykinin B2
      receptor in Chinese hamster ovary cells.
AB  - Rat bradykinin B2 receptor from unstimulated Chinese hamster ovary cells
      transfected with the corresponding cDNA has been isolated, and subsequent mass
      spectrometric analysis of multiple phosphorylated species and of the
      palmitoylation attachment site is described. Bradykinin B2 receptor was isolated
      on oligo(dT)-cellulose using N-(epsilon-maleimidocaproyloxy)succinimide-Met-Lys
      bradykinin coupled to a protected (dA)30-mer. This allowed a one-step isolation
      of the receptor on an oligo(dT)-cellulose column via variation solely of salt
      concentration. After enzymatic in-gel digestion, matrix-assisted laser desorption
      ionization and electrospray ion trap mass spectrometric analysis of the isolated
      rat bradykinin B2 receptor showed phosphorylation at Ser365, Ser371, Ser378,
      Ser380, and Thr374. Further phosphorylation at Tyr352 and Tyr161 was observed.
      Rat bradykinin receptor B2 receptor is also palmitoylated at Cys356. All of the
      phosphorylation sites except for Tyr161 cluster at the carboxyl-terminal domain
      of the receptor located on the cytoplasmic face of the cell membrane.
      Surprisingly, many of the post-translational modifications were shown by MSn mass
      spectroscopic analysis to be correlated pairwise, e.g. diphosphorylation at
      Ser365 and Ser371, at Ser378 and Ser380, and at Thr374 and Ser380 as well as
      mutually exclusive phosphorylation at Tyr352 and palmitoylation at Cys356. The
      last correlation may be involved in a receptor internalization motif. Pairwise
      correlations and mutual exclusion of phosphorylation and palmitoylation suggest
      critical roles of multiple post-translational modifications for the regulation of
      activity, coupling to intracelluar signaling pathways, and/or sequestration of
      the bradykinin receptor.

PMID- 10085088
TI  - Characterization of the p33 subunit of eukaryotic translation initiation factor-3
      from Saccharomyces cerevisiae.
AB  - Eukaryotic translation initiation factor-3 (eIF3) is a large multisubunit complex
      that binds to the 40 S ribosomal subunit and promotes the binding of methionyl
      tRNAi and mRNA. The molecular mechanism by which eIF3 exerts these functions is
      incompletely understood. We report here the cloning and characterization of
      TIF35, the Saccharomyces cerevisiae gene encoding the p33 subunit of eIF3. p33 is
      an essential protein of 30,501 Da that is required in vivo for initiation of
      protein synthesis. Glucose repression of TIF35 expressed from a GAL1 promoter
      results in depletion of both the p33 and p39 subunits. Expression of histidine
      tagged p33 in yeast in combination with Ni2+ affinity chromatography allows the
      isolation of a complex containing the p135, p110, p90, p39, and p33 subunits of
      eIF3. The p33 subunit binds both mRNA and rRNA fragments due to an RNA
      recognition motif near its C terminus. Deletion of the C-terminal 71 amino acid
      residues causes loss of RNA binding, but expression of the truncated form as the
      sole source of p33 nevertheless supports the slow growth of yeast. These results
      indicate that the p33 subunit of eIF3 plays an important role in the initiation
      phase of protein synthesis and that its RNA-binding domain is required for
      optimal activity.

PMID- 10085089
TI  - The thrombospondin receptor integrin-associated protein (CD47) functionally
      couples to heterotrimeric Gi.
AB  - Integrin-associated protein (IAP; CD47) is a thrombospondin receptor that forms a
      signaling complex with beta3 integrins resulting in enhanced alphavbeta3
      dependent cell spreading and chemotaxis and, in platelets, alphaIIbbeta3
      dependent spreading and aggregation. These actions of CD47 are all specifically
      abrogated by pertussis toxin treatment of cells. Here we report that CD47, its
      beta3 integrin partner, and Gi proteins form a stable, detergent-soluble complex
      that can be recovered by immunoprecipitation and affinity chromatography. Gialpha
      is released from this complex by treatment with GTP or AlF4. GTP and AlF4 also
      reduce the binding of CD47 to its agonist peptide (4N1K) derived from
      thrombospondin, indicating a direct association of CD47 with Gi. 4N1K peptide
      causes a rapid decrease in intraplatelet cyclic AMP levels, a Gi-dependent event
      necessary for aggregation. Finally, 4N1K stimulates the binding of GTPgamma35S to
      membranes from cells expressing IAP and alphavbeta3. This functional coupling of
      CD47 to heterotrimeric G proteins provides a mechanistic explanation for the
      biological effects of CD47 in a wide variety of systems.

PMID- 10085090
TI  - Oxidation regulates the inflammatory properties of the murine S100 protein
      S100A8.
AB  - The myeloid cell-derived calcium-binding murine protein, S100A8, is secreted to
      act as a chemotactic factor at picomolar concentrations, stimulating recruitment
      of myeloid cells to inflammatory sites. S100A8 may be exposed to oxygen
      metabolites, particularly hypochlorite, the major oxidant generated by activated
      neutrophils at inflammatory sites. Here we show that hypochlorite oxidizes the
      single Cys residue (Cys41) of S100A8. Electrospray mass spectrometry and SDS
      polyacrylamide gel electrophoresis analysis indicated that low concentrations of
      hypochlorite (40 microM) converted 70-80% of S100A8 to the disulfide-linked
      homodimer. The mass was 20,707 Da, 92 Da more than expected, indicating
      additional oxidation of susceptible amino acids (possibly methionine). Phorbol 12
      myristate 13-acetate activation of differentiated HL-60 granulocytic cells
      generated an oxidative burst that was sufficient to efficiently oxidize exogenous
      S100A8 within 10 min, and results implicate involvement of the myeloperoxidase
      system. Moreover, disulfide-linked dimer was identified in lung lavage fluid of
      mice with endotoxin-induced pulmonary injury. S100A8 dimer was inactive in
      chemotaxis and failed to recruit leukocytes in vivo. Positive chemotactic
      activity of recombinant Ala41S100A8 indicated that Cys41 was not essential for
      function and suggested that covalent dimerization may structurally modify
      accessibility of the chemotactic hinge domain. Disulfide-dependent dimerization
      may be a physiologically significant regulatory mechanism controlling S100A8
      provoked leukocyte recruitment.

PMID- 10085091
TI  - Cloning and characterization of human prostate coactivator ARA54, a novel protein
      that associates with the androgen receptor.
AB  - Androgen receptor (AR) is a member of the steroid receptor superfamily that may
      require coactivators for proper or maximal transactivation. Using a yeast two
      hybrid screening followed by mammalian cell analyses, we identified a novel
      ligand-dependent AR-associated protein, ARA54, which consists of 474 amino acids
      with a molecular mass of 54 kDa. We demonstrated that ARA54 might function as a
      preferential coactivator for AR-mediated transactivation in human prostate cancer
      DU145 cells. Interestingly, our data also showed that ARA54 could significantly
      enhance the transcriptional activity of LNCaP mutant AR (ARt877a) but not wild
      type AR or another mutant AR (ARe708k) in the presence of 10 nM 17beta-estradiol
      or 1 microM hydroxyflutamide. These results imply that both ARA54 and the
      positions of the AR mutation (877 versus 708) might contribute to the specificity
      of AR-mediated transactivation. Our findings further demonstrated that the C
      terminal domain of ARA54 can serve as a dominant negative inhibitor and exogenous
      full-length ARA54 can reverse this squelching effect on AR transcriptional
      activity. Co-expression of ARA54 with other AR coactivators, such as ARA70 or SRC
      1, showed additive stimulation of AR-mediated transactivation, which indicates
      that these cofactors may function individually as AR coactivators to induce AR
      target gene expression. Through our findings, we have identified and
      characterized a novel AR coactivator, ARA54, which may play an important role in
      the AR signaling pathway in human prostate.

PMID- 10085092
TI  - Preferential release of 11-cis-retinol from retinal pigment epithelial cells in
      the presence of cellular retinaldehyde-binding protein.
AB  - In photoreceptor cells of the retina, photoisomerization of 11-cis-retinal to all
      trans-retinal triggers phototransduction. Regeneration of 11-cis-retinal proceeds
      via a complex set of reactions in photoreceptors and in adjacent retinal pigment
      epithelial cells where all-trans-retinol is isomerized to 11-cis-retinol. Our
      results show that isomerization in vitro only occurs in the presence of apo
      cellular retinaldehyde-binding protein. This retinoid-binding protein may drive
      the reaction by mass action, overcoming the thermodynamically unfavorable
      isomerization. Furthermore, this 11-cis-retinol/11-cis-retinal-specific binding
      protein potently stimulates hydrolysis of endogenous 11-cis-retinyl esters but
      has no effect on hydrolysis of all-trans-retinyl esters. Apo-cellular
      retinaldehyde-binding protein probably exerts its effect by trapping the 11-cis
      retinol product. When retinoid-depleted retinal pigment epithelial microsomes
      were preincubated with different amounts of all-trans-retinol to form all-trans
      retinyl esters and then [3H]all-trans-retinol was added, as predicted, the
      specific radioactivity of [3H]all-trans-retinyl esters increased during
      subsequent reaction. However, the specific radioactivity of newly formed 11-cis
      retinol stayed constant during the course of the reaction, and it was largely
      unaffected by expansion of the all-trans-retinyl ester pool during the
      preincubation. The absence of dilution establishes that most of the ester pool
      does not participate in isomerization, which in turn suggests that a retinoid
      intermediate other than all-trans-retinyl ester is on the isomerization reaction
      pathway.

PMID- 10085093
TI  - Standard free energy for the hydrolysis of adenylylated T4 DNA ligase and the
      apparent pKa of lysine 159.
AB  - Equilibrium constants for the adenylylation of T4 DNA ligase have been measured
      at 10 pH values. The values, when plotted against pH, fit a titration curve
      corresponding to a pKa of 8.4 +/- 0.1. The simplest interpretation is that the
      apparent pKa is that of the 6-amino group of the AMP-accepting residue Lys159.
      Based on the pH dependence of the equilibrium constants, the value at pH 7.0 is
      0. 0213 at 25 degrees C, corresponding to DeltaG'o = +2.3 kcal mol-1. From this
      value and the standard free energy change of -10.9 kcal mol-1 for the hydrolysis
      of ATP to AMP and PPi, we calculate that DeltaG'o for the hydrolysis of the
      adenylyl-DNA ligase is -13.2 kcal mol-1. The presence of conserved basic amino
      acid residues in the catalytic domain, which are proximal to the active site in
      the homologous catalytic domain of T7 DNA ligase, suggests that the pKa of Lys159
      is perturbed downward by the electrostatic effects of nearby positively charged
      amino acid side chains. The lower than normal pKa 8.4 compared with 10.5 for the
      6-amino group of lysine and the high energy of the alpha,beta-phosphoanhydride
      linkage in ATP significantly facilitate adenylylation of the enzyme.

PMID- 10085094
TI  - Protein kinase Czeta is a negative regulator of protein kinase B activity.
AB  - Protein kinase B (PKB), also known as Akt or RAC-PK, is a serine/threonine kinase
      that can be activated by growth factors via phosphatidylinositol 3-kinase. In
      this article we show that PKCzeta but not PKCalpha and PKCdelta can co
      immunoprecipitate PKB from CHO cell lysates. Association of PKB with PKCzeta was
      also found in COS-1 cells transiently expressing PKB and PKCzeta, and moreover we
      found that this association is mediated by the AH domain of PKB. Stimulation of
      COS-1 cells with platelet-derived growth factor (PDGF) resulted in a decrease in
      the PKB-PKCzeta interaction. The use of kinase-inactive mutants of both kinases
      revealed that dissociation of the complex depends upon PKB activity. Analysis of
      the activities of the interacting kinases showed that PDGF-induced activation of
      PKCzeta was not affected by co-expression of PKB. However, both PDGF- and p110
      CAAX-induced activation of PKB were significantly abolished in cells co
      expressing PKCzeta. In contrast, co-expression of a kinase-dead PKCzeta mutant
      showed an increased induction of PKB activity upon PDGF treatment. Downstream
      signaling of PKB, such as the inhibition of glycogen synthase kinase-3, was also
      reduced by co-expression of PKCzeta. A clear inhibitory effect of PKCzeta was
      found on the constitutively active double PKB mutant (T308D/S473D). In summary,
      our results demonstrate that PKB interacts with PKCzeta in vivo and that PKCzeta
      acts as a negative regulator of PKB.

PMID- 10085095
TI  - Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse
      and human leukotriene B4 receptor-transfected cells.
AB  - The mouse leukotriene B4 receptor (m-BLTR) gene was cloned. Membrane fractions of
      human embryonic kidney 293 cells stably expressing m-BLTR demonstrated a high
      affinity and specific binding for leukotriene B4 (LTB4, Kd = 0.24 +/- 0.03 nM).
      In competition binding experiments, LTB4 was the most potent competitor (Ki =
      0.23 +/- 0.05 nM) followed by 20-hydroxy-LTB4 (Ki = 1.1 +/- 0.2 nM) and by 6
      trans-12-epi-LTB4 and LTD4 (Ki > 1 microM). In stably transfected Chinese hamster
      ovary cells, LTB4 inhibited forskolin-activated cAMP production and induced an
      increase of intracellular calcium, suggesting that this receptor is coupled to Gi
      and Go-like proteins. In Xenopus laevis melanophores transiently expressing m
      BLTR, LTB4 induced the aggregation of pigment granules, confirming the inhibition
      of cAMP production induced by LTB4. BLT receptors share significant sequence
      homology with chemokine receptors (CCR5 and CXCR4) that act as human
      immunodeficiency virus (HIV) coreceptors. However, among the 16 HIV/SIV strains
      tested, the human BLT receptor did not act as a coreceptor for virus entry into
      CD4-expressing cells based on infection and cell-cell fusion assays. In 5
      lipoxygenase-deficient mice, the absence of leukotriene B4 biosynthesis did not
      detectably alter m-BLT receptor binding in membranes obtained from glycogen
      elicited neutrophils. Isolation of the m-BLTR gene will form the basis of future
      experiments to elucidate the selective role of LTB4, as opposed to cysteinyl
      leukotrienes, in murine models of inflammation.

PMID- 10085096
TI  - The Saccharomyces cerevisiae YOR163w gene encodes a diadenosine 5', 5"'-P1,P6
      hexaphosphate (Ap6A) hydrolase member of the MutT motif (Nudix hydrolase) family.
AB  - The YOR163w open reading frame on chromosome XV of the Saccharomyces cerevisiae
      genome encodes a member of the MutT motif (nudix hydrolase) family of enzymes of
      Mr 21,443. By cloning and expressing this gene in Escherichia coli and S.
      cerevisiae, we have shown the product to be a (di)adenosine polyphosphate
      hydrolase with a previously undescribed substrate specificity. Diadenosine 5',5"'
      P1, P6-hexaphosphate is the preferred substrate, and hydrolysis in H218O shows
      that ADP and adenosine 5'-tetraphosphate are produced by attack at Pbeta and AMP
      and adenosine 5'-pentaphosphate are produced by attack at Palpha with a Km of 56
      microM and kcat of 0.4 s-1. Diadenosine 5',5"'-P1,P5-pentaphosphate, adenosine 5'
      pentaphosphate, and adenosine 5'-tetraphosphate are also substrates, but not
      diadenosine 5',5"'-P1,P4-tetraphosphate or other dinucleotides, mononucleotides,
      nucleotide sugars, or nucleotide alcohols. The enzyme, which was shown to be
      expressed in log phase yeast cells by immunoblotting, displays optimal activity
      at pH 6.9, 50 degrees C, and 4-10 mM Mg2+ (or 200 microM Mn2+). It has an
      absolute requirement for a reducing agent, such as dithiothreitol (1 mM), and is
      inhibited by Ca2+ with an IC50 of 3.3 mM and F- (noncompetitively) with a Ki of
      80 microM. Its function may be to eliminate potentially toxic dinucleoside
      polyphosphates during sporulation.

PMID- 10085097
TI  - Identification of multiple phosphoinositide-specific phospholipases D as new
      regulatory enzymes for phosphatidylinositol 3,4, 5-trisphosphate.
AB  - In the course of delineating the regulatory mechanism underlying
      phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) metabolism, we have
      discovered three distinct phosphoinositide-specific phospholipase D (PI-PLD)
      isozymes from rat brain, tentatively designated as PI-PLDa, PI-PLDb, and PI-PLDc.
      These enzymes convert [3H]PI(3,4,5)P3 to generate a novel inositol phosphate, D
      myo-[3H]inositol 3,4,5-trisphosphate ([3H]Ins(3,4,5)P3) and phosphatidic acid.
      These isozymes are predominantly associated with the cytosol, a notable
      difference from phosphatidylcholine PLDs. They are partially purified by a three
      step procedure consisting of DEAE, heparin, and Sephacryl S-200 chromatography.
      PI-PLDa and PI-PLDb display a high degree of substrate specificity for PI(3,4,
      5)P3, with a relative potency of PI(3,4,5)P3 >> phosphatidylinositol 3-phosphate
      (PI(3)P) or phosphatidylinositol 4-phosphate (PI(4)P) > phosphatidylinositol 4,5
      bisphosphate (PI(4,5)P2) > phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). In
      contrast, PI-PLDc preferentially utilizes PI(3)P as substrate, followed by, in
      sequence, PI(3,4,5)P3, PI(4)P, PI(3,4)P2, and PI(4,5)P2. Both PI(3, 4)P2 and
      PI(4,5)P2 are poor substrates for all three isozymes, indicating that the
      regulatory mechanisms underlying these phosphoinositides are different from that
      of PI(3,4,5)P3. None of these enzymes reacts with phosphatidylcholine,
      phosphatidylserine, or phosphatidylethanolamine. All three PI-PLDs are Ca2+
      dependent. Among them, PI-PLDb and PI-PLDc show maximum activities within a sub
      microM range (0.3 and 0.9 microM Ca2+, respectively), whereas PI-PLDa exhibits an
      optimal [Ca2+] at 20 microM. In contrast to PC-PLD, Mg2+ has no significant
      effect on the enzyme activity. All three enzymes require sodium deoxycholate for
      optimal activities; other detergents examined including Triton X-100 and Nonidet
      P-40 are, however, inhibitory. In addition, PI(4,5)P2 stimulates these isozymes
      in a dose-dependent manner. Enhancement in the enzyme activity is noted only when
      the molar ratio of PI(4,5)P2 to PI(3,4, 5)P3 is between 1:1 and 2:1.

PMID- 10085098
TI  - Bcl-xL blocks activation of related adhesion focal tyrosine kinase/proline-rich
      tyrosine kinase 2 and stress-activated protein kinase/c-Jun N-terminal protein
      kinase in the cellular response to methylmethane sulfonate.
AB  - The stress-activated protein kinase/c-Jun N-terminal protein kinase (JNK) is
      induced in response to ionizing radiation and other DNA-damaging agents. Recent
      studies indicate that activation of JNK is necessary for induction of apoptosis
      in response to diverse agents. Here we demonstrate that methylmethane sulfonate
      (MMS)-induced activation of JNK is inhibited by overexpression of the anti
      apoptotic protein Bcl-xL, but not by caspase inhibitors CrmA and p35. By
      contrast, UV-induced JNK activity is insensitive to Bcl-xL. The results
      demonstrate that treatment with MMS is associated with an increase in tyrosine
      phosphorylation of related adhesion focal tyrosine kinase (RAFTK)/proline-rich
      tyrosine kinase 2 (PYK2), an upstream effector of JNK and that this
      phosphorylation is inhibited by overexpression of Bcl-xL. Furthermore,
      overexpression of a dominant-negative mutant of RAFTK (RAFTK K-M) inhibits MMS
      induced JNK activation. The results indicate that inhibition of RAFTK
      phosphorylation by MMS in Bcl-xL cells is attributed to an increase in tyrosine
      phosphatase activity in these cells. Hence, treatment of Bcl-xL cells with sodium
      vanadate, a tyrosine phosphatase inhibitor, restores MMS-induced activation of
      RAFTK and JNK. These findings indicate that RAFTK-dependent induction of JNK in
      response to MMS is sensitive to Bcl-xL, but not to CrmA and p35, by a mechanism
      that inhibits tyrosine phosphorylation and thereby activation of RAFTK. Taken
      together, these findings support a novel role for Bcl-xL that is independent of
      the caspase cascade.

PMID- 10085099
TI  - Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a
      novel receptor.
AB  - Cripto-1 (CR-1) is a recently discovered protein of the epidermal growth factor
      family that fails to directly bind to any of the four known erb B type 1 receptor
      tyrosine kinases. The present study demonstrates that CR-1 indirectly induces
      tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor
      related receptors erb B-2 and erb B-3 in different mouse and human mammary
      epithelial cell lines. In addition, down-regulation of erb B-4 in NMuMG mouse
      mammary epithelial cells and in T47D human breast cancer cells, using an anti-erb
      B-4 blocking antibody or a hammerhead ribozyme vector targeted to erb B-4 mRNA,
      impairs the ability of CR-1 to fully activate mitogen-activated protein kinase.
      Finally, chemical cross-linking of 125I-CR-1 to mouse and human mammary
      epithelial cell membranes results in the labeling of two specific bands with a
      molecular weight of 130 and 60 kDa, suggesting that the CR-1 receptor represents
      a novel receptor structurally unrelated to any of the known type I receptor
      tyrosine kinases. In conclusion, these data demonstrate that CR-1, upon binding
      to an unknown receptor, can enhance the tyrosine kinase activity of erb B-4 and
      that a functional erb B-4 receptor is required for CR-1-induced MAPK activation.

PMID- 10085100
TI  - The interleukin-1 type 2 receptor gene displays immediate early gene
      responsiveness in glucocorticoid-stimulated human epidermal keratinocytes.
AB  - Human epidermal keratinocytes (HEKs) in primary culture (P2-P4) were used to
      study glucocorticoid (GC)-mediated transcription of the genes encoding the
      constitutively expressed interleukin-1 type 1 receptor (IL-1R1) and the inducible
      interleukin-1 type 2 receptor (IL-1R2). Utilizing Northern dot blot analysis and
      a quantitative reverse transcription-polymerase chain reaction protocol for IL
      1R1 and IL-1R2, dexamethasone and, in particular, the budesonide epimer R were
      shown to effectively and rapidly induce transcription from the IL-IR2 gene when
      compared with IL-1R1 or beta-actin RNA message levels in the same sample.
      Southern blot analysis of newly generated IL-1R2 reverse transcription-polymerase
      chain reaction products using end-labeled IL-1R2 intron probes suggested that GC
      enhancement of IL-1R2 expression was regulated primarily at the level of de novo
      transcription. GC-induced IL-1R2 gene transcription displayed features
      characteristic of a classical immediate early gene response, including a signal
      transduction function, a relatively low basal abundance, a rapid, transient
      induction, cycloheximide superinduction, actinomycin D suppression, and a rapid
      decay of IL-1R2 RNA message. Parallel time course kinetic analysis of IL-1R2 RNA
      message levels with Western immunoblotting revealed tight coupling of de novo IL
      IR2 gene transcription with translation of the IL-1R2 RNA message; a newly
      synthesized ( approximately 46-kDa) IL-1R2 protein was detected in the HEK growth
      medium as early as 1 h after budesonide epimer R treatment. These data indicate
      that different GC compounds can variably up-regulate the IL-1R2 response in HEKs
      through transcription-mediated mechanisms and, for the first time, suggest that a
      gene encoding a soluble cytokine receptor can respond like an immediate early
      gene.

PMID- 10085101
TI  - Molecular determinants for sodium-dependent activation of G protein-gated K+
      channels.
AB  - G protein-gated inwardly rectifying K+ channels (GIRKs) are activated by a direct
      interaction with Gbetagamma subunits and also by raised internal [Na+]. Both
      processes require the presence of phosphatidylinositol bisphosphate (PIP2). Here
      we show that the proximal C-terminal region of GIRK2 mediates the Na+-dependent
      activation of both the GIRK2 homomeric channels and the GIRK1/GIRK2 heteromeric
      channels. Within this region, GIRK2 has an aspartate at position 226, whereas
      GIRK1 has an asparagine at the equivalent position (217). A single point
      mutation, D226N, in GIRK2, abolished the Na+-dependent activation of both the
      homomeric and heteromeric channels. Neutralizing a nearby negative charge, E234S
      had no effect. The reverse mutation in GIRK1, N217D, was sufficient to restore
      Na+-dependent activation to the GIRK1N217D/GIRK2D226N heteromeric channels. The
      D226N mutation did not alter either the single channel properties or the ability
      of these channels to be activated via the m2-muscarinic receptor. PIP2
      dramatically increased the open probability of GIRK1/GIRK2 channels in the
      absence of Na+ or Gbetagamma but did not preclude further activation by Na+,
      suggesting that Na+ is not acting simply to promote PIP2 binding to GIRKs. We
      conclude that aspartate 226 in GIRK2 plays a crucial role in Na+-dependent gating
      of GIRK1/GIRK2 channels.

PMID- 10085102
TI  - Peptide-bound major histocompatibility complex class I molecules associate with
      tapasin before dissociation from transporter associated with antigen processing.
AB  - Major histocompatibility complex (MHC) class I molecules present antigenic
      peptides to CD8 T cells. The peptides are generated in the cytosol, then
      translocated across the membrane of the endoplasmic reticulum by the transporter
      associated with antigen processing (TAP). TAP is a trimeric complex consisting of
      TAP1, TAP2, and tapasin (TAP-A) as indicated for human cells by reciprocal
      coprecipitation with anti-TAP1/2 and anti-tapasin antibodies, respectively. TAP1
      and TAP2 are required for the peptide transport. Tapasin is involved in the
      association of class I with TAP and in the assembly of class I with peptide. The
      mechanisms of tapasin function are still unknown. Moreover, there has been no
      evidence for a murine tapasin analogue, which has led to the suggestion that
      murine MHC class I binds directly to TAP1/2. In this study, we have cloned the
      mouse analogue of tapasin. The predicted amino acid sequence showed 78% identity
      to human tapasin with identical consensus sequences of signal peptide, N-linked
      glycosylation site, transmembrane domain and double lysine motif. However, there
      was less homology (47%) found at the predicted cytosolic domain, and in addition,
      mouse tapasin is 14 amino acids longer than the human analogue at the C terminus.
      This part of the molecule may determine the species specificity for interaction
      with MHC class I or TAP1/2. Like human tapasin, mouse tapasin binds both to
      TAP1/2 and MHC class I. In TAP2-mutated RMA-S cells, both TAP1 and MHC class I
      were coprecipitated by anti-tapasin antiserum indicative of association of
      tapasin with TAP1 but not TAP2. With crosslinker-modified peptides and purified
      microsomes, anti-tapasin coprecipitated both peptide-bound MHC class I and
      TAP1/2. In contrast, anti-calreticulin only coprecipitated peptide-free MHC class
      I molecules. This difference in association with peptide-loaded class I suggests
      that tapasin functions later than calreticulin during MHC class I assembly, and
      controls peptide loading onto MHC class I molecules in the endoplasmic reticulum.

PMID- 10085103
TI  - Purification and characterization from rat kidney membranes of a novel platelet
      activating factor (PAF)-dependent transacetylase that catalyzes the hydrolysis of
      PAF, formation of PAF analogs, and C2-ceramide.
AB  - We have previously identified two enzyme activities that transfer the acetyl
      group from platelet-activating factor (PAF) in a CoA-independent manner to
      lysoplasmalogen or sphingosine in HL-60 cells, endothelial cells, and a variety
      of rat tissues. These were termed as PAF:lysoplasmalogen (lysophospholipid)
      transacetylase and PAF:sphingosine transacetylase, respectively. In the present
      study, we have solubilized and purified this PAF-dependent transacetylase 13,700
      fold from rat kidney membranes (mitochondrial plus microsomal membranes) based on
      the PAF:lysoplasmalogen transacetylase activity. The mitochondria and microsomes
      were prepared and washed three times, then solubilized with 0.04% Tween 20 at a
      detergent/protein (w/w) ratio of 0.1. The solubilized fractions from mitochondria
      and microsomes were combined and subjected to sequential column chromatographies
      on DEAE-Sepharose, hydroxyapatite, phenyl-Sepharose, and chromatofocusing. The
      enzyme was further purified by native-polyacrylamide gel electrophoresis (PAGE)
      and affinity gel matrix in which the competitive inhibitor of the enzyme, 1-O
      hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphoethanolamine was covalently
      attached to the CH-Sepharose. On SDS-PAGE, the purified enzyme showed a single
      homogeneous band with an apparent molecular mass of 40 kDa. The purified enzyme
      catalyzed transacetylation of the acetyl group not only from PAF to
      lysoplasmalogen forming plasmalogen analogs of PAF, but also to sphingosine
      producing N-acetylsphingosine (C2-ceramide). In addition, this enzyme acted as a
      PAF-acetylhydrolase in the absence of lipid acceptor molecules. These results
      suggest that PAF-dependent transacetylase is an enzyme that modifies the cellular
      functions of PAF through generation of other diverse lipid mediators.

PMID- 10085104
TI  - Growth hormone-dependent differentiation of 3T3-F442A preadipocytes requires
      Janus kinase/signal transducer and activator of transcription but not mitogen
      activated protein kinase or p70 S6 kinase signaling.
AB  - The signals mediating growth hormone (GH)-dependent differentiation of 3T3-F442A
      preadipocytes under serum-free conditions have been studied. GH priming of cells
      was required before the induction of terminal differentiation by a combination of
      epidermal growth factor, tri-iodothyronine, and insulin. Cellular depletion of
      Janus kinase-2 (JAK-2) using antisense oligodeoxynucleotides (ODNs) prevented GH
      stimulated JAK-2 and signal transducer and activator of transcription (STAT)-5
      tyrosine phosphorylation and severely attenuated the ability of GH to promote
      differentiation. Although p42(MAPK)/p44(MAPK) mitogen-activated protein kinases
      were activated during GH priming, treatment of cells with PD 098059, which
      prevented activation of these kinases, did not block GH priming. However,
      antisense ODN-mediated depletion of mitogen-activated protein kinases from the
      cells showed that their expression was necessary for terminal differentiation.
      Similarly, although p70(s6k) was activated during GH priming, pretreatment of
      cells with rapamycin, which prevented the activation of p70(s6k), had no effect
      on GH priming. However, rapamycin did partially block epidermal growth factor,
      tri-iodothyronine, and insulin-stimulated terminal differentiation. By contrast,
      cellular depletion of STAT-5 with antisense ODNs completely abolished the ability
      of GH to promote differentiation. These results indicate that JAK-2, acting
      specifically via STAT-5, is necessary for GH-dependent differentiation of 3T3
      F442A preadipocytes. Activation of p42(MAPK)/p44(MAPK) and p70(s6k) is not
      essential for the promotion of differentiation by GH, although these signals are
      required for GH-independent terminal differentiation.

PMID- 10085105
TI  - A cell type-specific constitutive point mutant of the common beta-subunit of the
      human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)
      3, and IL-5 receptors requires the GM-CSF receptor alpha-subunit for activation.
AB  - The high affinity receptor for human granulocyte-macrophage colony-stimulating
      factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMRalpha) and a
      common signal-transducing beta-subunit (hbetac) that is shared with the
      interleukin-3 and -5 receptors. We have previously identified a constitutively
      active extracellular point mutant of hbetac, I374N, that can confer factor
      independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B.
      J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287). This
      restricted activity suggested the involvement of cell type-specific signaling
      molecules in the activation of this mutant. We report here that one such molecule
      is the mouse GMRalpha (mGMRalpha) subunit, since introduction of mGMRalpha, but
      not hGMRalpha, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred
      factor independence. Experiments utilizing mouse/human chimeric GMRalpha subunits
      indicated that the species specificity lies in the extracellular domain of
      GMRalpha. Importantly, the requirement for mGMRalpha correlated with the ability
      of I374N (but not wild-type hbetac) to constitutively associate with mGMRalpha.
      Expression of I374N in human factor-dependent UT7 cells also led to factor
      independent proliferation, with concomitant up-regulation of hGMRalpha surface
      expression. Taken together, these findings suggest a critical role for
      association with GMRalpha in the constitutive activity of I374N.

PMID- 10085106
TI  - Intracellular trafficking pathways in the assembly of connexins into gap
      junctions.
AB  - Trafficking pathways underlying the assembly of connexins into gap junctions were
      examined using living COS-7 cells expressing a range of connexin-aequorin (Cx
      Aeq) chimeras. By measuring the chemiluminescence of the aequorin fusion partner,
      the translocation of oligomerized connexins from intracellular stores to the
      plasma membrane was shown to occur at different rates that depended on the
      connexin isoform. Treatment of COS-7 cells expressing Cx32-Aeq and Cx43-Aeq with
      brefeldin A inhibited the movement of these chimera to the plasma membrane by 84
      +/- 4 and 88 +/- 4%, respectively. Nocodazole treatment of the cells expressing
      Cx32-Aeq and Cx43-Aeq produced 29 +/- 16 and 4 +/- 7% inhibition, respectively.
      In contrast, the transport of Cx26 to the plasma membrane, studied using a
      construct (Cx26/43T-Aeq) in which the short cytoplasmic carboxyl-terminal tail of
      Cx26 was replaced with the extended carboxyl terminus of Cx43, was inhibited 89
      +/- 5% by nocodazole and was minimally affected by exposure of cells to brefeldin
      A (17 +/-11%). The transfer of Lucifer yellow across gap junctions between cells
      expressing wild-type Cx32, Cx43, and the corresponding Cx32-Aeq and Cx43-Aeq
      chimeras was reduced by nocodazole treatment and abolished by brefeldin A
      treatment. However, the extent of dye coupling between cells expressing wild-type
      Cx26 or the Cx26/43T-Aeq chimeras was not significantly affected by brefeldin A
      treatment, but after nocodazole treatment, transfer of dye to neighboring cells
      was greatly reduced. These contrasting effects of brefeldin A and nocodazole on
      the trafficking properties and intercellular dye transfer are interpreted to
      suggest that two pathways contribute to the routing of connexins to the gap
      junction.

PMID- 10085107
TI  - Altered ligand rebinding kinetics due to distal-side effects in hemoglobin chico
      (Lysbeta66(E10) --> thr).
AB  - Hb Chico is an unusual human hemoglobin variant that has lowered oxygen affinity,
      but unaltered cooperativity and anion sensitivity. Previous studies showed these
      features to be associated with distal-side heme pocket alterations that confer
      increased structural rigidity on the molecule and that increase water content in
      the beta-chain heme pocket. We report here that the extent of nanosecond geminate
      rebinding of oxygen to the variant and its isolated beta-chains is appreciably
      decreased. Structural alterations in this variant decrease its oxygen
      recombination rates without significantly altering rates of migration out of the
      heme pocket. Data analysis indicates that one or more barriers that impede
      rebinding of oxygen from docking sites in the heme pocket are increased, with
      less consequence for CO rebinding. Resonance Raman spectra show no significant
      alterations in spectral regions sensitive to interactions between the heme iron
      and the proximal histidine residue, confirming that the functional differences in
      the variant are due to distal-side heme pocket alterations. These effects are
      discussed in the context of a schematic representation of heme pocket wells and
      barriers that could aid the design of novel hemoglobins with altered ligand
      affinity without loss of the normal allosteric responses that facilitate
      unloading of oxygen to respiring tissues.

PMID- 10085108
TI  - Characterization of a novel, non-peptidyl antagonist of the human glucagon
      receptor.
AB  - We have identified a series of potent, orally bioavailable, non-peptidyl,
      triarylimidazole and triarylpyrrole glucagon receptor antagonists. 2-(4-Pyridyl)
      5-(4-chlorophenyl)-3-(5-bromo-2-propyloxyphenyl)p yrr ole (L-168,049), a
      prototypical member of this series, inhibits binding of labeled glucagon to the
      human glucagon receptor with an IC50 = 3. 7 +/- 3.4 nM (n = 7) but does not
      inhibit binding of labeled glucagon-like peptide to the highly homologous human
      glucagon-like peptide receptor at concentrations up to 10 microM. The binding
      affinity of L-168,049 for the human glucagon receptor is decreased 24-fold by the
      inclusion of divalent cations (5 mM). L-168,049 increases the apparent EC50 for
      glucagon stimulation of adenylyl cyclase in Chinese hamster ovary cells
      expressing the human glucagon receptor and decreases the maximal glucagon
      stimulation observed, with a Kb (concentration of antagonist that shifts the
      agonist dose-response 2-fold) of 25 nM. These data suggest that L-168,049 is a
      noncompetitive antagonist of glucagon action. Inclusion of L-168, 049 increases
      the rate of dissociation of labeled glucagon from the receptor 4-fold, confirming
      that the compound is a noncompetitive glucagon antagonist. In addition, we have
      identified two putative transmembrane domain residues, phenylalanine 184 in
      transmembrane domain 2 and tyrosine 239 in transmembrane domain 3, for which
      substitution by alanine reduces the affinity of L-168,049 46- and 4. 5-fold,
      respectively. These mutations do not alter the binding of labeled glucagon,
      suggesting that the binding sites for glucagon and L-168,049 are distinct.

PMID- 10085109
TI  - Phenylethanolamine N-methyltransferase gene expression. Sp1 and MAZ potential for
      tissue-specific expression.
AB  - Phenylethanolamine N-methyltransferase (PNMT) promoter-luciferase reporter gene
      constructs (pGL3RP863, pGL3RP444, and pGL3RP392) transfected into COS1, RS1,
      PC12, NIH/3T3, or Neuro2A cells showed the highest basal luciferase activity in
      the Neuro2A cells. DNase I footprinting with Neuro2A cell nuclear extract
      identified protected PNMT promoter regions spanning the -168/-165 and -48/-45
      base pair Sp1/Egr-1 binding sites. Gel mobility shift assays and transient
      transfection assays using site-directed mutant PNMT promoter-luciferase reporter
      gene constructs indicated that the elevated basal luciferase activity in the
      Neuro2A cells was mediated by Sp-1. Furthermore, activation of the PNMT promoter
      by Sp1 depends on both its binding affinity for its cognate target sequences and
      its intracellular concentrations. When Sp1 levels were increased through an
      expression plasmid, luciferase reporter gene expression rose well beyond basal
      wild-type levels, even with either Sp1 binding element mutated. Finally, another
      transcription factor expressed in the Neuro2A cells competes with Sp1 by
      interacting with DNA sequences 3' to the -48 base pair Sp1 site to prevent Sp1
      binding and induction of the PNMT promoter. The DNA consensus sequence,
      Southwestern analysis, and gel mobility shift assays with antibodies identify MAZ
      as the competitive factor. These findings suggest that Sp1 may potentially
      contribute to the tissue-specific expression of the PNMT gene, with the
      competition between Sp1 and MAZ conferring additional tissue-specific control.

PMID- 10085110
TI  - Overexpression of RelA causes G1 arrest and apoptosis in a pro-B cell line.
AB  - NF-kappaB/Rel family proteins form a network of post-translationally regulated
      transcription factors that respond to a variety of extracellular stimuli and
      mediate distinct cellular responses. These responses include cytokine gene
      expression, regulated cell cycle activation, and both the protection from and
      induction of the cell death program. To examine the function of individual Rel
      family proteins in B cell development and resolve their role in the signaling of
      apoptosis, we used a tetracycline-regulated gene expression system to overexpress
      either c-Rel or RelA in the transformed pro-B cell line 220-8. Elevated levels of
      RelA, but not c-Rel, induced a G1 cell cycle arrest followed by apoptosis. Both
      the DNA binding and transactivation domains of RelA were required for this
      effect. When RelA was overexpressed in the immature B cell line WEHI 231 or the
      mature B cell line M12, neither cell cycle arrest nor apoptosis was evident. The
      differential effects of elevated RelA levels in these cell lines suggests that
      susceptibility to NF-kappaB-induced apoptosis may reflect a relevant selection
      event during B cell development.

PMID- 10085111
TI  - Identification of quinone-binding and heme-ligating residues of the smallest
      membrane-anchoring subunit (QPs3) of bovine heart mitochondrial
      succinate:ubiquinone reductase.
AB  - The smallest membrane-anchoring subunit (QPs3) of bovine heart
      succinate:ubiquinone reductase was overexpressed in Escherichia coli JM109 as a
      glutathione S-transferase fusion protein using the expression vector pGEX2T/QPs3.
      The yield of soluble active recombinant glutathione S-transferase-QPs3 fusion
      protein was isopropyl-1-thio-beta-D-galactopyranoside concentration-, induction
      growth time-, temperature-, and medium-dependent. Maximum yield of soluble
      recombinant fusion protein was obtained from cells harvested 3.5 h post-isopropyl
      1-thio-beta-D-galactopyranoside (0.4 mM)-induction growth at 25 degrees C in 2.0%
      tryptone, 0.5% yeast extract, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl2, 20 mM glucose
      (SOC medium) containing 440 mM sorbitol and 2.5 mM betaine. QPs3 was released
      from the fusion protein by proteolytic cleavage with thrombin. Isolated
      recombinant QPs3 shows one protein band in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis that corresponds to subunit V of mitochondrial
      succinate:ubiquinone reductase. Although purified recombinant QPs3 is dispersed
      in 0.01% dodecylmaltoside, it is in a highly aggregated form, with an apparent
      molecular mass of more than 1 million. The recombinant QPs3 binds ubiquinone,
      causing a spectral blue shift. Upon titration of the recombinant protein with
      ubiquinone, a saturation behavior is observed, suggesting that the binding is
      specific and that recombinant QPs3 may be in the functionally active state. Two
      amino acid residues, serine 33 and tyrosine 37, in the putative ubiquinone
      binding domain of QPs3 are involved in ubiquinone binding because the S33A- or
      Y37A-substituted recombinant QPs3s do not cause the spectral blue shift of
      ubiquinone. Although recombinant QPs3 contains little cytochrome b560 heme, the
      spectral characteristics of cytochrome b560 are reconstituted upon addition of
      hemin chloride. Reconstituted cytochrome b560 in recombinant QPs3 shows a EPR
      signal at g = 2.92. Histidine residues at positions 46 and 60 are responsible for
      heme ligation because the H46N- or H60N-substituted QPs3 fail to restore
      cytochrome b560 upon addition of hemin chloride.

PMID- 10085112
TI  - Effect of buffer conditions on the position of tRNA on the 70 S ribosome as
      visualized by cryoelectron microscopy.
AB  - The effect of buffer conditions on the binding position of tRNA on the
      Escherichia coli 70 S ribosome have been studied by means of three-dimensional
      (3D) cryoelectron microscopy. Either deacylated tRNAfMet or fMet-tRNAfMet were
      bound to the 70 S ribosomes, which were programmed with a 46-nucleotide mRNA
      having AUG codon in the middle, under two different buffer conditions
      (conventional buffer: containing Tris and higher Mg2+ concentration [10-15 mM];
      and polyamine buffer: containing Hepes, lower Mg2+ concentration [6 mM], and
      polyamines). Difference maps, obtained by subtracting 3D maps of naked control
      ribosome in the corresponding buffer from the 3D maps of tRNA.ribosome complexes,
      reveal the distinct locations of tRNA on the ribosome. The position of deacylated
      tRNAfMet depends on the buffer condition used, whereas that of fMet-tRNAfMet
      remains the same in both buffer conditions. The acylated tRNA binds in the
      classical P site, whereas deacylated tRNA binds mostly in an intermediate P/E
      position under the conventional buffer condition and mostly in the position
      corresponding to the classical P site, i. e. in the P/P state, under the
      polyamine buffer conditions.

PMID- 10085113
TI  - Cleavage of atrophin-1 at caspase site aspartic acid 109 modulates cytotoxicity.
AB  - Dentatorubropallidoluysian atrophy (DRPLA) is one of eight autosomal dominant
      neurodegenerative disorders characterized by an abnormal CAG repeat expansion
      which results in the expression of a protein with a polyglutamine stretch of
      excessive length. We have reported recently that four of the gene products
      (huntingtin, atrophin-1 (DRPLA), ataxin-3, and androgen receptor) associated with
      these open reading frame triplet repeat expansions are substrates for the
      cysteine protease cell death executioners, the caspases. This led us to
      hypothesize that caspase cleavage of these proteins may represent a common step
      in the pathogenesis of each of these four neurodegenerative diseases. Here we
      present evidence that caspase cleavage of atrophin-1 modulates cytotoxicity and
      aggregate formation. Cleavage of atrophin-1 at Asp109 by caspases is critical for
      cytotoxicity because a mutant atrophin-1 that is resistant to caspase cleavage is
      associated with significantly decreased toxicity. Further, the altered cellular
      localization within the nucleus and aggregate formation associated with the
      expanded form of atrophin-1 are completely suppressed by mutation of the caspase
      cleavage site at Asp109. These results provide support for the toxic fragment
      hypothesis whereby cleavage of atrophin-1 by caspases may be an important step in
      the pathogenesis of DRPLA. Therefore, inhibiting caspase cleavage of the
      polyglutamine-containing proteins may be a feasible therapeutic strategy to
      prevent cell death.

PMID- 10085114
TI  - Identification and characterization of potential effector molecules of the Ras
      related GTPase Rap2.
AB  - In search for effectors of the Ras-related GTPase Rap2, we used the yeast two
      hybrid method and identified the C-terminal Ras/Rap interaction domain of the Ral
      exchange factors (RalGEFs) Ral GDP dissociation stimulator (RalGDS), RalGDS-like
      (RGL), and RalGDS-like factor (Rlf). These proteins, which also interact with
      activated Ras and Rap1, are effectors of Ras and mediate the activation of Ral in
      response to the activation of Ras. Here we show that the full-length RalGEFs
      interact with the GTP-bound form of Rap2 in the two-hybrid system as well as in
      vitro. When co-transfected in HeLa cells, an activated Rap2 mutant (Rap2Val-12)
      but not an inactive protein (Rap2Ala-35) co-immunoprecipitates with RalGDS and
      Rlf; moreover, Rap2-RalGEF complexes can be isolated from the particulate
      fraction of transfected cells and were localized by confocal microscopy to the
      resident compartment of Rap2, i.e. the endoplasmic reticulum. However, the
      overexpression of activated Rap2 neither leads to the activation of the Ral
      GTPase via RalGEFs nor inhibits Ras-dependent Ral activation in vivo. Several
      hypotheses that could explain these results, including compartmentalization of
      proteins involved in signal transduction, are discussed. Our results suggest that
      in cells, the interaction of Rap2 with RalGEFs might trigger other cellular
      responses than activation of the Ral GTPase.

PMID- 10085115
TI  - Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2
      structure and activity.
AB  - We have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for
      crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces
      cerevisiae and have grown crystals using microseeding techniques. Phosphorylation
      of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the
      binary CDK2-cyclin A complex. Phosphorylated CDK2 exhibits histone H1 kinase
      activity corresponding to approximately 0.3% of that observed with the fully
      activated phosphorylated CDK2-cyclin A complex. Fluorescence measurements have
      shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone
      substrate and ATP and decreases its affinity for ADP. By contrast,
      phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The
      crystal structures of the ATP-bound forms of phosphorylated CDK2 and
      unphosphorylated CDK2 have been solved at 2.1-A resolution. The structures are
      similar, with the major difference occurring in the activation segment, which is
      disordered in phosphorylated CDK2. The greater mobility of the activation segment
      in phosphorylated CDK2 and the absence of spontaneous crystallization suggest
      that phosphorylated CDK2 may adopt several different mobile states. The majority
      of these states are likely to correspond to inactive conformations, but a small
      fraction of phosphorylated CDK2 may be in an active conformation and hence
      explain the basal activity observed.

PMID- 10085116
TI  - Transcription initiation at the flagellin promoter by RNA polymerase carrying
      sigma28 from Salmonella typhimurium.
AB  - The sigma subunit of RNA polymerase is a critical factor in positive control of
      transcription initiation. Primary sigma factors are essential proteins required
      for vegetative growth, whereas alternative sigma factors mediate transcription in
      response to various stimuli. Late gene expression during flagellum biosynthesis
      in Salmonella typhimurium is dependent upon an alternative sigma factor, sigma28,
      the product of the fliA gene. We have characterized the intermediate complexes
      formed by sigma28 holoenzyme on the pathway to open complex formation.
      Interactions with the promoter for the flagellin gene fliC were analyzed using
      DNase I and KMnO4 footprinting over a range of temperatures. We propose a model
      in which closed complexes are established in the upstream region of the promoter,
      including the -35 element, but with little significant contact in the -10 element
      or downstream regions of the promoter. An isomerization event extends the DNA
      contacts into the -10 element and the start site, with loss of the most distal
      upstream contacts accompanied by DNA melting to form open complexes. Melting
      occurs efficiently even at 16 degrees C. Once open complexes have formed, they
      are unstable to heparin challenge even in the presence of nucleoside
      triphosphates, which have been observed to stabilize open complexes at rRNA
      promoters.

PMID- 10085117
TI  - Crystal structure of the B subunit of Escherichia coli heat-labile enterotoxin
      carrying peptides with anti-herpes simplex virus type 1 activity.
AB  - Two chimeric proteins, consisting of the B subunit of Escherichia coli heat
      labile enterotoxin with different peptides fused to the COOH-terminal ends, have
      been crystallized and their three-dimensional structure determined. The two
      extensions correspond to (a) a nonapeptide representing the COOH-terminal
      sequence of the small subunit of herpes simplex virus type 1 ribonucleotide
      reductase and (b) a 27-amino acid long peptide, corresponding to the COOH
      terminal end of the catalytic subunit (POL) of DNA polymerase from the same
      virus. Both proteins crystallize in the P41212 space group with one pentameric
      molecule per asymmetric unit, corresponding to a solvent content of about 75%.
      The overall conformation of the B subunit pentamer in the two chimeric proteins,
      which consists of five identical polypeptide chains, is very similar to that in
      the native AB complex and conforms strictly to 5-fold symmetry. On the contrary,
      the peptide extensions are essentially disordered: in the case of the
      nonapeptide, only 5 and 6 amino acids were, respectively, positioned in two
      monomers, while in the other three only 2 residues are ordered. The extension is
      fully confined to the surface of the pentamer opposite to the face that interacts
      with the membrane and consequently it does not interfere with the ability of the
      B subunit to interact with membrane receptors. Moreover, the conformational
      flexibility of the two peptide extensions could be correlated to their propensity
      for proteolytic processing and consequent release of a biologically active
      molecule into cultured cells.

PMID- 10085118
TI  - The alpha-helical domain of Galphat determines specific interaction with
      regulator of G protein signaling 9.
AB  - RGS proteins (regulators of G protein signaling) are potent accelerators of the
      intrinsic GTPase activity of G protein alpha subunits (GAPs), thus controlling
      the response kinetics of a variety of cell signaling processes. Most RGS domains
      that have been studied have relatively little GTPase activating specificity
      especially for G proteins within the Gi subfamily. Retinal RGS9 is unique in its
      ability to act synergistically with a downstream effector cGMP phosphodiesterase
      to stimulate the GTPase activity of the alpha subunit of transducin, Galphat.
      Here we report another unique property of RGS9: high specificity for Galphat. The
      core (RGS) domain of RGS9 (RGS9) stimulates Galphat GTPase activity by 10-fold
      and Galphai1 GTPase activity by only 2-fold at a concentration of 10 microM.
      Using chimeric Galphat/Galphai1 subunits we demonstrated that the alpha-helical
      domain of Galphat imparts this specificity. The functional effects of RGS9 were
      well correlated with its affinity for activated Galpha subunits as measured by a
      change in fluorescence of a mutant Galphat (Chi6b) selectively labeled at Cys
      210. Kd values for RGS9 complexes with Galphat and Galphai1 calculated from the
      direct binding and competition experiments were 185 nM and 2 microM,
      respectively. The gamma subunit of phosphodiesterase increases the GAP activity
      of RGS9. We demonstrate that this is because of the ability of Pgamma to increase
      the affinity of RGS9 for Galphat. A distinct, nonoverlapping pattern of RGS and
      Pgamma interaction with Galphat suggests a unique mechanism of effector-mediated
      GAP function of the RGS9.

PMID- 10085119
TI  - Membrane topology of the mammalian CMP-sialic acid transporter.
AB  - Nucleotide sugar transporters form a family of distantly related membrane
      proteins of the Golgi apparatus and the endoplasmic reticulum. The first
      transporter sequences have been identified within the last 2 years. However,
      information about the secondary and tertiary structure for these molecules has
      been limited to theoretical considerations. In the present study, an epitope
      insertion approach was used to investigate the membrane topology of the CMP
      sialic acid transporter. Immunofluorescence studies were carried out to analyze
      the orientation of the introduced epitopes in semipermeabilized cells. Both an
      amino-terminally introduced FLAG sequence and a carboxyl-terminal hemagglutinin
      tag were found to be oriented toward the cytosol. Results obtained with CMP
      sialic acid transporter variants that contained the hemagglutinin epitope in
      potential intermembrane loop structures were in good correlation with the
      presence of 10 transmembrane regions. This building concept seems to be preserved
      also in other mammalian and nonmammalian nucleotide sugar transporters. Moreover,
      the functional analysis of the generated mutants demonstrated that insertions in
      or very close to membrane-spanning regions inactivate the transport process,
      whereas those in hydrophilic loop structures have no detectable effect on the
      activity. This study points the way toward understanding structure-function
      relationships of nucleotide sugar transporters.

PMID- 10085120
TI  - The activation of the c-Jun N-terminal kinase and p38 mitogen-activated protein
      kinase signaling pathways protects HeLa cells from apoptosis following
      photodynamic therapy with hypericin.
AB  - In this study, we elucidate signaling pathways induced by photodynamic therapy
      (PDT) with hypericin. We show that PDT rapidly activates JNK1 while irreversibly
      inhibiting ERK2 in several cancer cell lines. In HeLa cells, sustained PDT
      induced JNK1 and p38 mitogen-activated protein kinase (MAPK) activations overlap
      the activation of a DEVD-directed caspase activity, poly(ADP-ribose) polymerase
      (PARP) cleavage, and the onset of apoptosis. The caspase inhibitors
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) and benzyloxycarbonyl
      Asp-Glu-Val-Asp-fluoromethylketone (zDEVD-fmk) protect cells against apoptosis
      and inhibit DEVD-specific caspase activity and PARP cleavage without affecting
      JNK1 and p38 MAPK activations. Conversely, stable overexpression of CrmA, the
      serpin-like inhibitor of caspase-1 and caspase-8, has no effect on PDT-induced
      PARP cleavage, apoptosis, or JNK1/p38 activations. Cell transfection with the
      dominant negative inhibitors of the c-Jun N-terminal kinase (JNK) pathway, SEK-AL
      and TAM-67, or pretreatment with the p38 MAPK inhibitor PD169316 enhances PDT
      induced apoptosis. A similar increase in PDT-induced apoptosis was observed by
      expression of the dual specificity phosphatase MKP-1. The simultaneous inhibition
      of both stress kinases by pretreating cells with PD169316 after transfection with
      either TAM-67 or SEK-AL produces a more pronounced sensitizing effect. Cell
      pretreatment with the p38 inhibitor PD169316 causes faster kinetics of DEVD
      caspase activation and PARP cleavage and strongly oversensitizes the cells to
      apoptosis following PDT. These observations indicate that the JNK1 and p38 MAPK
      pathways play an important role in cellular resistance against PDT-induced
      apoptosis with hypericin.

PMID- 10085121
TI  - MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N
      terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional
      activation in endothelial cells.
AB  - Smad proteins are essential components of the intracellular signaling pathways
      utilized by members of the transforming growth factor-beta (TGF-beta) superfamily
      of growth factors. Certain Smad proteins (e.g. Smad1, -2, and -3) can act as
      regulated transcriptional activators, a process that involves phosphorylation of
      these proteins by activated TGF-beta superfamily receptors. We demonstrate that
      the intracellular kinase mitogen-activated protein kinase kinase kinase-1 (MEKK
      1), an upstream activator of the stress-activated protein kinase/c-Jun N-terminal
      kinase pathway, can participate in Smad2-dependent transcriptional events in
      cultured endothelial cells. A constitutively active form of MEKK-1 but not
      mitogen-activated protein kinase kinase-1 (MEK-1) or TGF-beta-activated kinase-1,
      two distinct intracellular kinases, can specifically activate a Gal4-Smad2 fusion
      protein, and this effect correlates with an increase in the phosphorylation state
      of the Smad2 protein. These effects do not require the presence of the C-terminal
      SSXS motif of Smad2 that is the site of TGF-beta type 1 receptor-mediated
      phosphorylation. Activation of Smad2 by active MEKK-1 results in enhanced Smad2
      Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation
      of Smad protein-transcriptional coactivator interactions in endothelial cells.
      Overexpression of Smad7 can inhibit the MEKK-1-mediated stimulation of Smad2
      transcriptional activity. A physiological level of fluid shear stress, a known
      activator of endogenous MEKK-1 activity in endothelial cells, can stimulate Smad2
      mediated transcriptional activity. These data demonstrate a novel mechanism for
      activation of Smad protein-mediated signaling in endothelial cells and suggest
      that Smad2 may act as an integrator of diverse stimuli in these cells.

PMID- 10085122
TI  - Ca2+ sensitization and potentiation of the maximum level of myofibrillar ATPase
      activity caused by mutations of troponin T found in familial hypertrophic
      cardiomyopathy.
AB  - Human wild-type cardiac troponin T, I, C and five troponin T mutants (I79N, R92Q,
      F110I, E244D, and R278C) causing familial hypertrophic cardiomyopathy were
      expressed in Escherichia coli, and then were purified and incorporated into
      rabbit cardiac myofibrils using a troponin exchange technique. The Ca2+-sensitive
      ATPase activity of these myofibrillar preparations was measured in order to
      examine the functional consequences of these troponin mutations. An I79N troponin
      T mutation was found to cause a definite increase in Ca2+ sensitivity of the
      myofibrillar ATPase activity without inducing any significant change in the
      maximum level of ATPase activity. A detailed analysis indicated the inhibitory
      action of troponin I to be impaired by the I79N troponin T mutation. Two more
      troponin T mutations (R92Q and R278C) were also found to have a Ca2+-sensitizing
      effect without inducing any change in maximum ATPase activity. Two other troponin
      T mutations (F110I and E244D) had no Ca2+-sensitizing effects on the ATPase
      activity, but remarkably potentiated the maximum level of ATPase activity. These
      findings indicate that hypertrophic cardiomyopathy-linked troponin T mutations
      have at least two different effects on the Ca2+-sensitive ATPase activity, Ca2+
      sensitization and potentiation of the maximum level of the ATPase activity.

PMID- 10085123
TI  - CREB binding protein coordinates the function of multiple transcription factors
      including nuclear factor I to regulate phosphoenolpyruvate carboxykinase (GTP)
      gene transcription.
AB  - Nuclear factor I (NFI) binds to a region of the phosphoenolpyruvate carboxykinase
      (GTP) (PEPCK) gene promoter adjacent to the cAMP regulatory element (CRE) and
      inhibits the induction of transcription from the gene promoter caused by the
      catalytic subunit of protein kinase A. In vivo footprinting studies demonstrated
      that both the CRE and the NFI-binding site are occupied by transcription factors,
      regardless of the presence of factors that stimulate (dibutyryl cAMP or
      dexamethasone) or inhibit (insulin) transcription from the PEPCK gene promoter.
      The NFI effects on transcription from the PEPCK gene promoter were observed even
      in the absence of the NFI binding site, suggesting the possibility of other
      weaker binding sites on the promoter or an interaction of NFI with a
      transcriptional co-activator. A mammalian two-hybrid system was used to
      demonstrate direct interaction between the transactivation domain of NFI-C and
      the CREB binding domain of the CREB-binding protein (CBP). Overexpression of a
      gene fragment encoding the CREB binding domain of CBP stimulates transcription
      from the PEPCK gene promoter. The inhibitory effect of NFI on transcription of
      the PEPCK gene induced by the catalytic subunit of protein kinase A appears to be
      the result of an interaction between NFI and the CREB-binding protein in which
      NFI competes with CREB for binding to the CREB-binding site on CBP. In contrast,
      glucocorticoids and thyroid hormone use the steroid hormone receptor binding
      domain of CBP to stimulate transcription from the PEPCK gene promoter. NFI-A
      combines with dexamethasone or thyroid hormone in an additive manner to stimulate
      PEPCK gene transcription. We conclude that CBP coordinates the action of the
      multiple factors known to control transcription of the PEPCK gene.

PMID- 10085124
TI  - Molecular cloning of two new human paralogs of 85-kDa cytosolic phospholipase A2.
AB  - Two new cloned human cDNAs encode paralogs of the 85-kDa cytosolic phospholipase
      A2 (cPLA2). We propose to call these cPLA2beta (114 kDa) and cPLA2gamma (61 kDa),
      giving the name cPLA2alpha to the well known 85-kDa enzyme. cPLA2beta mRNA is
      expressed more highly in cerebellum and pancreas and cPLA2gamma more highly in
      cardiac and skeletal muscle. Sequence-tagged site mapping places cPLA2beta on
      chromosome 15 in a region near a phosphoinositol bisphosphate phosphatase. The
      mRNA for cPLA2beta is spliced only at a very low level, and Northern blots in 24
      tissues show exclusively the unspliced form. cPLA2beta has much lower activity on
      2-arachidonoyl-phosphatidylcholine liposomes than either of the other two
      enzymes. Its sequence contains a histidine motif characteristic of the catalytic
      center of caspase proteases of the apoptotic cascade but no region characteristic
      of the catalytic cysteine. Sequence-tagged site mapping places cPLA2gamma on
      chromosome 19 near calmodulin. cPLA2gamma lacks the C2 domain, which gives
      cPLA2alpha its Ca2+ sensitivity, and accordingly cPLA2gamma has no dependence
      upon calcium, although cPLA2beta does. cPLA2gamma contains a prenyl group-binding
      site motif and appears to be largely membrane-bound. cPLA2alpha residues
      activated by phosphorylation do not appear to be well conserved in either new
      enzyme. In contrast, all three previously known catalytic residues, as well as
      one additional essential arginine, Arg-566 in cPLA2alpha, are conserved in both
      new enzyme sequences. Mutagenesis shows strong dependence on these residues for
      catalytic activity of all three enzymes.

PMID- 10085125
TI  - Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein
      lipase.
AB  - Lipoprotein lipase and the receptor-associated protein (RAP) bind to overlapping
      sites on the low density lipoprotein receptor-related protein/alpha2
      macroglobulin receptor (LRP). We have investigated if lipoprotein lipase
      interacts with the RAP binding but structurally distinct receptor
      sortilin/neurotensin receptor-3. We show, by chemical cross-linking and surface
      plasmon resonance analysis, that soluble sortilin binds lipoprotein lipase with
      an affinity similar to that of LRP. The binding was inhibited by heparin and RAP
      and by the newly discovered sortilin ligand neurotensin. In 35S-labeled 3T3-L1
      adipocytes treated with the cross-linker dithiobis(succinimidyl propionate),
      lipoprotein lipase-containing complexes were isolated by anti-sortilin
      antibodies. To elucidate function in cells, sortilin-negative Chinese hamster
      ovary cells were transfected with full-length sortilin and shown to express about
      8% of the receptors on the cell surface. These cells degraded 125I-labeled
      lipoprotein lipase much faster than the wild-type cells. The degradation was
      inhibited by unlabeled lipoprotein lipase, indicating a saturable pathway, and by
      RAP and heparin. Moreover, inhibition by the weak base chloroquine suggested that
      degradation occurs in an acidic vesicle compartment. The results demonstrate that
      sortilin is a multifunctional receptor that binds lipoprotein lipase and, when
      expressed on the cell surface, mediates its endocytosis and degradation.

PMID- 10085126
TI  - Positive regulation of the BRCA1 promoter.
AB  - Inherited mutations in the BRCA1 gene, presumably leading to loss of function,
      confer susceptibility to breast and ovarian neoplasms and are thought to be
      responsible for approximately 2.5-5% of all breast cancers. It has been suggested
      that alternative mechanisms, such as disruption of transcription, may also be
      involved in the suppression of BRCA1 gene expression/function in breast cancers.
      Therefore, we initiated studies on the BRCA1 transcriptional promoter. Utilizing
      systematic promoter deletions and transient transfection assays, a 36-base pair
      region was determined to be important for the positive regulation of BRCA1
      transcription. Deletion of this positive regulatory region resulted in a
      significant loss of promoter activity. Utilizing DNA binding assays, proteins
      with specific affinities for the positive regulatory region were detected.
      Disruption of the DNA-protein complexes could affect normal BRCA1 transcription
      and may contribute to breast cancer susceptibility.

PMID- 10085127
TI  - Transcriptional activation following cerebral ischemia in mice of a promoter
      deleted nitric oxide synthase-2 gene.
AB  - Nitric oxide synthase (NOS)-2 is transcriptionally activated in a wide variety of
      injurious conditions, including cerebral ischemia, and the resulting nitric oxide
      is implicated both in tissue damage and recovery. Studies in vitro suggest that
      the proximal region of the NOS-2 promoter is obligatory for gene activation by
      proinflammatory cytokines. However, following cerebral ischemia in a NOS-2 gene
      deficient mouse in which this region and exons 1-4 have been deleted, we find
      temporal and spatial expression, identical to wild-type, from a previously
      unidentified promoter region. The resulting protein is predicted to lack the
      first 113 amino acids and is NOS-2-incompetent. Fortuitously, this gene-deficient
      mouse presents a unique opportunity to determine more about the mechanisms of NOS
      2 gene regulation in vivo.

PMID- 10085128
TI  - Mitochondrial telomere-binding protein from Candida parapsilosis suggests an
      evolutionary adaptation of a nonspecific single-stranded DNA-binding protein.
AB  - The mitochondrial genome in a number of organisms is represented by linear DNA
      molecules with defined terminal structures. The telomeres of linear mitochondrial
      DNA (mtDNA) of yeast Candida parapsilosis consist of tandem arrays of large
      repetitive units possessing single-stranded 5' extension of about 110
      nucleotides. Recently we identified the first mitochondrial telomere-binding
      protein (mtTBP) that specifically binds a sequence derived from the extreme end
      of C. parapsilosis linear mtDNA and protects it from attack by various DNA
      modifying enzymes (Tomaska, L'., Nosek, J., and Fukuhara, H. (1997) J. Biol.
      Chem. 272, 3049-3059). Here we report the isolation of MTP1, the gene encoding
      mtTBP of C. parapsilosis. Sequence analysis revealed that mtTBP shares homology
      with several bacterial and mitochondrial single-stranded DNA-binding proteins
      that nonspecifically bind to single-stranded DNA with high affinity. Recombinant
      mtTBP displays a preference for the telomeric 5' overhang of C. parapsilosis
      mtDNA. The heterologous expression of a mtTBP-GFP fusion protein resulted in its
      localization to the mitochondria but was unable to functionally substitute for
      the loss of the S. cerevisiae homologue Rimlp. Analysis of the MTP1 gene and its
      translation product mtTBP may provide an insight into the evolutionary origin of
      linear mitochondrial genomes and the role it plays in their replication and
      maintenance.

PMID- 10085129
TI  - Regulation of G protein-coupled receptor kinases by caveolin.
AB  - G protein-coupled receptor kinases (GRKs) have been principally characterized by
      their ability to phosphorylate and desensitize G protein-coupled receptors.
      However, recent studies suggest that GRKs may have more diverse protein/protein
      interactions in cells. Based on the identification of a consensus caveolin
      binding motif within the pleckstrin homology domain of GRK2, we tested the direct
      binding of purified full-length GRK2 to various glutathione S-transferase
      caveolin-1 fusion proteins, and we discovered a specific interaction of GRK2 with
      the caveolin scaffolding domain. Interestingly, analysis of GRK1 and GRK5, which
      lack a pleckstrin homology domain, revealed in vitro binding properties similar
      to those of GRK2. Maltose-binding protein caveolin and glutathione S-transferase
      GRK fusion proteins were used to map overlapping regions in the N termini of both
      GRK2 and GRK5 that appear to mediate conserved GRK/caveolin interactions. In vivo
      association of GRK2 and caveolin was suggested by co-fractionation of GRK2 with
      caveolin in A431 and NIH-3T3 cells and was further supported by co
      immunoprecipitation of GRK2 and caveolin in COS-1 cells. Functional significance
      for the GRK/caveolin interaction was demonstrated by the potent inhibition of GRK
      mediated phosphorylation of both receptor and peptide substrates by caveolin-1
      and -3 scaffolding domain peptides. These data reveal a novel mode for the
      regulation of GRKs that is likely to play an important role in their cellular
      function.

PMID- 10085130
TI  - ErbB-2 amplification inhibits down-regulation and induces constitutive activation
      of both ErbB-2 and epidermal growth factor receptors.
AB  - ErbB-2/HER2 is an important signaling partner for the epidermal growth factor
      receptor (EGFR). Overexpression of erbB-2 is also associated with poor prognosis
      in breast cancer. To investigate how erbB-2 amplification affects its
      interactions with the EGFR, we used a human mammary epithelial cell system in
      which erbB-2 expression was increased 7-20-fold by gene transfection. We found
      that amplification of erbB-2 caused constitutive activation of erbB-2 as well as
      ligand-independent activation of the EGFR. Overexpression of erbB-2 strongly
      inhibited erbB-2 down-regulation following transactivation by EGFR.
      Significantly, down-regulation of activated EGFR was also inhibited by erbB-2
      amplification, resulting in enhanced ligand-dependent activation of the EGFR. The
      rate of EGFR endocytosis was not affected by erbB-2 overexpression, but the rate
      of lysosomal targeting was significantly reduced. In addition, erbB-2
      overexpression promoted rapid recycling of activated EGFR back to the cell
      surface and decreased ligand dissociation from the EGFR. Our data suggest that
      overexpression of erbB-2 inhibits both its down-regulation and that of the EGFR.
      The net effect is increased signaling through the EGFR system.

PMID- 10085131
TI  - Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5)
      phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl
      terminus.
AB  - The binding of CC chemokines to CC chemokine receptor 5 (CCR5) triggers cellular
      responses that, generally, are only transient in nature. To explore the potential
      role of G protein-coupled receptor kinases (GRKs) in the regulation of CCR5, we
      performed phosphorylation experiments in a rat basophilic leukemia cell line
      stably expressing CCR5. The ability of various CCR5 ligands to stimulate calcium
      mobilization in these cells correlated with their ability to induce receptor
      phosphorylation, desensitization, internalization, and GRK association with the
      receptor. Aminooxypentane-RANTES, a potent inhibitor of human immunodeficiency
      virus infection, has been proposed to act through enhanced CCR5 internalization
      and inhibition of receptor recycling. Aminooxypentane-RANTES profoundly induced
      CCR5 phosphorylation, but had no effect on CCR1. In permeabilized rat basophilic
      leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited
      RANTES-induced receptor phosphorylation. Consistent with a role for these kinases
      in CCR5 regulation, 1-2 x 10(5) copies of GRK2 or GRK3 were found to be expressed
      in peripheral blood leukocytes. Phosphoamino acid analysis revealed that RANTES
      induced CCR5 phosphorylation selectively occurs on serine residues. Our findings
      with receptor mutants indicate that serine residues at positions 336, 337, 342,
      and 349 represent GRK phosphorylation sites on CCR5. This study demonstrates that
      chemokines differ in their ability to induce CCR5 phosphorylation and
      desensitization and provides a molecular mechanism for the agonist-induced
      attenuation of CCR5 signaling.

PMID- 10085132
TI  - Requirements of protein kinase cdelta for catalytic function. Role of glutamic
      acid 500 and autophosphorylation on serine 643.
AB  - Recently, we reported that, in contrast to protein kinase C (PKC)alpha and
      betaII, PKCdelta does not require phosphorylation of a specific threonine
      (Thr505) in the activation loop for catalytic competence (Stempka et al. (1997)
      J. Biol. Chem. 272, 6805-6811). Here, we show that the acidic residue glutamic
      acid 500 (Glu500) in the activation loop is important for the catalytic function
      of PKCdelta. A Glu500 to valine mutant shows 76 and 73% reduced kinase activity
      toward autophosphorylation and substrate phosphorylation, respectively. With
      regard to thermal stability and inhibition by the inhibitors Go6976 and Go6983
      the mutant does not differ from the wild type, indicating that the general
      conformation of the molecule is not altered by the site-directed mutagenesis.
      Thus, Glu500 in the activation loop of PKCdelta might take over at least part of
      the role of the phosphate groups on Thr497 and Thr500 of PKCalpha and betaII,
      respectively. Accordingly, PKCdelta exhibits kinase activity and is able to
      autophosphorylate probably without posttranslational modification.
      Autophosphorylation of PKCdelta in vitro occurs on Ser643, as demonstrated by
      matrix-assisted laser desorption ionization mass spectrometry of tryptic peptides
      of autophosphorylated PKCdelta wild type and mutants. A peptide containing this
      site is phosphorylated also in vivo, i.e. in recombinant PKCdelta purified from
      baculovirus-infected insect cells. A Ser643 to alanine mutation indicates that
      autophosphorylation of Ser643 is not essential for the kinase activity of
      PKCdelta. Probably additional (auto)phosphorylation site(s) exist that have not
      yet been identified.

PMID- 10085133
TI  - Scavenger receptor BI mediates the selective uptake of oxidized cholesterol
      esters by rat liver.
AB  - High density lipoprotein (HDL) can protect low density lipoprotein (LDL) against
      oxidation. Oxidized cholesterol esters from LDL can be transferred to HDL and
      efficiently and selectively removed from the blood circulation by the liver and
      adrenal in vivo. In the present study, we investigated whether scavenger receptor
      BI (SR-BI) is responsible for this process. At 30 min after injection, the
      selective uptake of oxidized cholesterol esters from HDL for liver and adrenal
      was 2.3- and 2.6-fold higher, respectively, than for native cholesterol esters,
      whereas other tissues showed no significant difference. The selective uptake of
      oxidized cholesterol esters from HDL by isolated liver parenchymal cells could be
      blocked for 75% by oxidized LDL and for 50% by phosphatidylserine liposomes, both
      of which are known substrates of SR-BI. In vivo uptake of oxidized cholesterol
      esters from HDL by parenchymal cells decreased by 64 and 81% when rats were
      treated with estradiol and a high cholesterol diet, respectively, whereas Kupffer
      cells showed 660 and 475% increases, respectively. These contrasting changes in
      oxidized cholesterol ester uptake were accompanied by similar contrasting changes
      in SR-BI expression of parenchymal and Kupffer cells. The rates of SR-BI-mediated
      selective uptake of oxidized and native cholesterol esters were analyzed in SR-BI
      transfected Chinese hamster ovary cells. SR-BI-mediated selective uptake was 3.4
      fold higher for oxidized than for native cholesterol esters (30 min of
      incubation). It is concluded that in addition to the selective uptake of native
      cholesterol esters, SR-BI is responsible for the highly efficient selective
      uptake of oxidized cholesterol esters from HDL and thus forms an essential
      mediator in the HDL-associated protection system for atherogenic oxidized
      cholesterol esters.

PMID- 10085134
TI  - A differential requirement for the COOH-terminal region of the epidermal growth
      factor (EGF) receptor in amphiregulin and EGF mitogenic signaling.
AB  - The epidermal growth factor receptor (EGFR) mediates the actions of a family of
      bioactive peptides that include epidermal growth factor (EGF) and amphiregulin
      (AR). Here we have studied AR and EGF mitogenic signaling in EGFR-devoid NR6
      fibroblasts that ectopically express either wild type EGFR (WT) or a truncated
      EGFR that lacks the three major sites of autophosphorylation (c'1000). COOH
      terminal truncation of the EGFR significantly impairs the ability of AR to (i)
      stimulate DNA synthesis, (ii) elicit Elk-1 transactivation, and (iii) generate
      sustained enzymatic activation of mitogen-activated protein kinase. EGFR
      truncation had no significant effect on AR binding to receptor but did result in
      defective GRB2 adaptor function. In contrast, EGFR truncation did not impair EGF
      mitogenic signaling, and in c'1000 cells EGF was able to stimulate the
      association of ErbB2 with GRB2 and SHC. Elk-1 transactivation was monitored when
      either ErbB2 or a truncated dominant-negative ErbB2 mutant (ErbB2-(1-813)) was
      overexpressed in cells. Overexpression of full-length ErbB2 resulted in a strong
      constitutive transactivation of Elk-1 in c'1000 but only slightly stimulated Elk
      1 in WT or parental NR6 cells. Conversely, overexpression of ErbB2-(1-813)
      inhibited EGF-stimulated Elk-1 transactivation in c'1000 but not in WT cells.
      Thus, the cytoplasmic tail of the EGFR plays a critical role in AR mitogenic
      signaling but is dispensable for EGF, since EGF-activated truncated EGFRs can
      signal through ErbB2.

PMID- 10085135
TI  - Angiostatin formation involves disulfide bond reduction and proteolysis in
      kringle 5 of plasmin.
AB  - Plasmin is processed in the conditioned medium of HT1080 fibrosarcoma cells
      producing fragments with the domain structures of the angiogenesis inhibitor,
      angiostatin, and microplasmin. Angiostatin consists of kringle domains 1-4 and
      part of kringle 5, while microplasmin consists of the remainder of kringle 5 and
      the serine proteinase domain. Our findings indicate that formation of
      angiostatin/microplasmin involves reduction of plasmin by a plasmin reductase
      followed by proteolysis of the reduced enzyme. We present evidence that the
      Cys461-Cys540 and Cys511-Cys535 disulfide bonds in kringle 5 of plasmin were
      reduced by plasmin reductase. Plasmin reductase activity was secreted by HT1080
      and Chinese hamster ovary cells and the human mammary carcinoma cell lines MCF-7,
      MDA231, and BT20 but not by the monocyte/macrophage cell line THP-1. Neither
      primary foreskin fibroblasts, blood monocyte/macrophages, nor macrovascular or
      microvascular endothelial cells secreted detectable plasmin reductase. In
      contrast, cultured bovine and rat vascular smooth muscle cells secreted small but
      reproducible levels of plasmin reductase. Reduction of the kringle 5 disulfide
      bonds triggered cleavage at either Arg529-Lys530 or two other positions C
      terminal of Cys461 in kringle 5 by a serine proteinase. Plasmin autoproteolysis
      could account for the cleavage, although another proteinase was mostly
      responsible in HT1080 conditioned medium. Three serine proteinases with apparent
      Mr of 70, 50, and 39 were purified from HT1080 conditioned medium, one or more of
      which could contribute to proteolysis of reduced plasmin.

PMID- 10085136
TI  - Interactions between two cytoskeleton-associated tyrosine kinases: calcium
      dependent tyrosine kinase and focal adhesion tyrosine kinase.
AB  - The calcium-dependent tyrosine kinase (CADTK), also known as
      Pyk2/RAFTK/CAKbeta/FAK2, is a cytoskeleton-associated tyrosine kinase. We
      compared CADTK regulation with that of the highly homologous focal adhesion
      tyrosine kinase (FAK). First, we generated site-specific CADTK mutants. Mutation
      of Tyr402 eliminated autophosphorylation and significantly decreased kinase
      activity. Mutation of Tyr881, a putative Src kinase phosphorylation site
      predicted to bind Grb2, had little effect on CADTK regulation. Src family
      tyrosine kinases resulted in CADTK tyrosine phosphorylation even when co
      expressed with the Tyr402/Tyr881 double mutant, suggesting that Src/Fyn etc.
      phosphorylate additional tyrosine residues. Interestingly, CADTK tyrosine
      phosphorylated FAK when both were transiently expressed, but FAK did not
      phosphorylate CADTK. Biochemical experiments confirmed direct CADTK
      phosphorylation of FAK. This phosphorylation utilized tyrosine residues other
      than Tyr397, Tyr925, or Tyr576/Tyr577, suggesting that new SH2-binding sites
      might be created by CADTK-dependent FAK phosphorylation. Last, expression of the
      CADTK carboxyl terminus (CRNK) abolished CADTK but not FAK autophosphorylation.
      In contrast, FAK carboxyl terminus overexpression inhibited both FAK and CADTK
      autophosphorylation, suggesting that a FAK-dependent cytoskeletal function may be
      necessary for CADTK activation. Thus, CADTK and FAK, which both bind to some, but
      not necessarily the same, cytoskeletal elements, may be involved in coordinate
      regulation of cytoskeletal structure and signaling.

PMID- 10085137
TI  - Identification and characterization of the fifth membrane-type matrix
      metalloproteinase MT5-MMP.
AB  - A new member of the membrane-type matrix metalloproteinase (MT-MMP) subfamily
      tentatively named MT5-MMP was isolated from mouse brain cDNA library. It is
      predicted to contain (i) a candidate signal sequence, (ii) a propeptide region
      with the highly conserved PRCGVPD sequence, (iii) a potential furin recognition
      motif RRRRNKR, (iv) a zinc-binding catalytic domain, (v) a hemopexin-like domain,
      (vi) a 24-residue hydrophobic domain as a potential transmembrane domain, and
      (vii) a short cytosolic domain. Reverse transcriptase-polymerase chain reaction
      analysis of its transcripts indicates that MT5-MMP is expressed in a brain
      specific manner consistent with the origin of its EST clone from cerebellum. It
      is also highly expressed during embryonic development at stages day 11 and 15.
      Like other MT-MMPs, MT5-MMP specifically activates progelatinase A when co
      expressed in Madin-Darby canine kidney cells. Its ability to activate
      progelatinase A is dependent on its proteolytic activity since a mutation
      converting Glu to Ala in the zinc binding motif HE255LGH renders MT5-MMP inactive
      against progelatinase A. In contrast to other MT-MMPs, MT5-MMP tends to shed from
      cell surface as soluble proteinases, thus offering flexibility as both a cell
      bound and soluble proteinase for extracellular matrix remodeling processes. Taken
      together, these properties serve to distinguish MT5-MMP as a versatile MT-MMP
      playing an important role in extracellular matrix remodeling events in the brain
      and during embryonic development.

PMID- 10085138
TI  - Processing of the fibrillin-1 carboxyl-terminal domain.
AB  - To investigate the processing and general properties of the fibrillin-1 carboxyl
      terminal domain, three protein expression constructs have been developed as
      follows: one without the domain, one with the domain, and one with a mutation
      near the putative proteolytic processing site. The constructs have been expressed
      in two eukaryotic model systems, baculoviral and CHO-K1. Post-translational
      modifications that normally occur in fibrillin-1, including glycosylation, signal
      peptide cleavage, and carboxyl-terminal processing, occur in the three constructs
      in both cell systems. Amino-terminal sequencing of secreted protein revealed
      leader sequence processing at two sites, a primary site between Gly-24/Ala-25 and
      a secondary site of Ala-27/Asn-28. Processing of the carboxyl-terminal domain
      could be observed by migration differences in SDS-polyacrylamide gel
      electrophoresis and was evident in both mammalian and insect cells. Immunological
      identification by Western blotting confirmed the loss of the expected region. The
      failure of both cell systems to process the mutant construct shows that the multi
      basic sequence is the site of proteolytic processing. Cleavage of the fibrillin-1
      carboxyl-terminal domain occurred intracellularly in CHO-K1 cells in an early
      secretory pathway compartment as demonstrated by studies with secretion blocking
      agents. This finding, taken with the multi-basic nature of the cleavage site and
      observed calcium sensitivity of cleavage, suggests that the processing enzyme is
      a secretory pathway resident furin-like protease.

PMID- 10085139
TI  - Internalization of the TXA2 receptor alpha and beta isoforms. Role of the
      differentially spliced cooh terminus in agonist-promoted receptor
      internalization.
AB  - Thromboxane A2 (TXA2) potently stimulates platelet aggregation and smooth muscle
      constriction and is thought to play a role in myocardial infarction,
      atherosclerosis, and bronchial asthma. The TXA2 receptor (TXA2R) is a member of
      the G protein-coupled receptor family and is found as two alternatively spliced
      isoforms, alpha (343 residues) and beta (407 residues), which share the first 328
      residues. In the present report, we demonstrate by enzyme-linked immunosorbent
      assay and immunofluorescence microscopy that the TXA2Rbeta, but not the
      TXA2Ralpha, undergoes agonist-induced internalization when expressed in HEK293
      cells as well as several other cell types. Various dominant negative mutants were
      used to demonstrate that the internalization of the TXA2Rbeta is dynamin-, GRK-,
      and arrestin-dependent in HEK293 cells, suggesting the involvement of receptor
      phosphorylation and clathrin-coated pits in this process. Interestingly, the
      agonist-stimulated internalization of both the alpha and beta isoforms, but not
      of a mutant truncated after residue 328, can be promoted by overexpression of
      arrestin-3, identifying the C-tails of both receptors as necessary in arrestin-3
      interaction. Simultaneous mutation of two dileucine motifs in the C-tail of
      TXA2Rbeta did not affect agonist-promoted internalization. Analysis of various C
      tail deletion mutants revealed that a region between residues 355 and 366 of the
      TXA2Rbeta is essential for agonist-promoted internalization. These data
      demonstrate that alternative splicing of the TXA2R plays a critical role in
      regulating arrestin binding and subsequent receptor internalization.

PMID- 10085140
TI  - ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth
      factor-beta signaling.
AB  - Upon transforming growth factor-beta (TGF-beta) binding to its cognate receptor,
      Smad3 and Smad4 form heterodimers and transduce the TGF-beta signal to the
      nucleus. In addition to the Smad pathway, another pathway involving a member of
      the mitogen-activated protein kinase kinase kinase family of kinases, TGF-beta
      activated kinase-1 (TAK1), is required for TGF-beta signaling. However, it is
      unknown how these pathways function together to synergistically amplify TGF-beta
      signaling. Here we report that the transcription factor ATF-2 (also called CRE
      BP1) is bound by a hetero-oligomer of Smad3 and Smad4 upon TGF-beta stimulation.
      ATF-2 is one member of the ATF/CREB family that binds to the cAMP response
      element, and its activity is enhanced after phosphorylation by stress-activated
      protein kinases such as c-Jun N-terminal kinase and p38. The binding between ATF
      2 and Smad3/4 is mediated via the MH1 region of the Smad proteins and the basic
      leucine zipper region of ATF-2. TGF-beta signaling also induces the
      phosphorylation of ATF-2 via TAK1 and p38. Both of these actions are shown to be
      responsible for the synergistic stimulation of ATF-2 trans-activating capacity.
      These results indicate that ATF-2 plays a central role in TGF-beta signaling by
      acting as a common nuclear target of both Smad and TAK1 pathways.

PMID- 10085141
TI  - Effect of epidermal growth factor receptor internalization on regulation of the
      phospholipase C-gamma1 signaling pathway.
AB  - The epidermal growth factor receptor (EGFR) ligands, epidermal growth factor
      (EGF), and transforming growth factor-alpha (TGFalpha) elicit differential
      postendocytic processing of ligand and receptor molecules, which impacts long
      term cell signaling outcomes. These differences arise from the higher affinity of
      the EGF-EGFR interaction versus that of TGFalpha-EGFR in the acidic conditions of
      sorting endosomes. To determine whether EGFR occupancy in endosomes might also
      affect short-term signaling events, we examined activation of the phospholipase C
      gamma1 (PLC-gamma1) pathway, an event shown to be essential for growth factor
      induced cell motility. We found that EGF continues to stimulate maximal tyrosine
      phosphorylation of EGFR following internalization, while, as expected, TGFalpha
      stimulates markedly less. The resulting higher level of receptor activation by
      EGF, however, did not yield higher levels of phosphatidylinositol (4,5)
      bisphosphate (PIP2) hydrolysis over those stimulated by TGFalpha. By altering the
      ratio of activated receptors between the cell surface and the internalized
      compartment, we found that only cell surface receptors effectively participate in
      PLC function. In contrast to PIP2 hydrolysis, PLC-gamma1 tyrosine phosphorylation
      correlated linearly with the total level of Tyr(P)-EGFR stimulated by either
      ligand, indicating that the functional deficiency of internal EGFR cannot be
      attributed to an inability to interact with and phosphorylate signaling proteins.
      We conclude that EGFR signaling through the PLC pathway is spatially restricted
      at a point between PLC-gamma1 phosphorylation and PIP2 hydrolysis, perhaps
      because of limited access of EGFR-bound PLC-gamma1 to its substrate in endocytic
      trafficking organelles.

PMID- 10085142
TI  - Calpain inhibitor I increases beta-amyloid peptide production by inhibiting the
      degradation of the substrate of gamma-secretase. Evidence that substrate
      availability limits beta-amyloid peptide production.
AB  - The calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) has been reported
      to have complex effects on the production of the beta-amyloid peptide (Abeta). In
      this study, the effects of ALLN on the processing of the amyloid precursor
      protein (APP) to Abeta were examined in 293 cells expressing APP or the C
      terminal 100 amino acids of APP (C100). In cells expressing APP or low levels of
      C100, ALLN increased Abeta40 and Abeta42 secretion at low concentrations,
      decreased Abeta40 and Abeta42 secretion at high concentrations, and increased
      cellular levels of C100 in a concentration-dependent manner by inhibiting C100
      degradation. Low concentrations of ALLN increased Abeta42 secretion more
      dramatically than Abeta40 secretion. ALLN treatment of cells expressing high
      levels of C100 did not alter cellular C100 levels and inhibited Abeta40 and
      Abeta42 secretion with similar IC50 values. These results suggest that C100 can
      be processed both by gamma-secretase and by a degradation pathway that is
      inhibited by low concentrations of ALLN. The data are consistent with inhibition
      of gamma-secretase by high concentrations of ALLN but do not support previous
      assertions that ALLN is a selective inhibitor of the gamma-secretase producing
      Abeta40. Rather, Abeta42 secretion may be more dependent on C100 substrate
      concentration than Abeta40 secretion.

PMID- 10085143
TI  - Ligand binding properties of the very low density lipoprotein receptor. Absence
      of the third complement-type repeat encoded by exon 4 is associated with reduced
      binding of Mr 40,000 receptor-associated protein.
AB  - The very low density lipoprotein receptor (VLDLR) binds, among other ligands, the
      Mr 40,000 receptor-associated protein (RAP) and a variety of serine proteinase
      serpin complexes, including complexes of the proteinase urokinase-type
      plasminogen activator (uPA) with the serpins plasminogen activator inhibitor-1
      (PAI-1) and protease nexin-1 (PN-1). We have analyzed the binding of RAP, uPA.PAI
      1, and uPA.PN-1 to two naturally occurring VLDLR variants, VLDLR-I, containing
      all eight complement-type repeats, and VLDLR-III, lacking the third complement
      type repeat, encoded by exon 4. VLDLR-III displayed approximately 4-fold lower
      binding of RAP than VLDLR-I and approximately 10-fold lower binding of the most C
      terminal one of the three domains of RAP. In contrast, the binding of uPA.PAI-1
      and uPA.PN-1 to the two VLDLR variants was indistinguishable. Surprisingly,
      uPA.PN-1, but not uPA.PAI-1, competed RAP binding to both VLDLR variants. These
      observations show that the third complement-type repeat plays a crucial role in
      maintaining the contact sites needed for optimal recognition of RAP, but does not
      affect the proteinase-serpin complex contact sites, and that two ligands can show
      full cross-competition without sharing the same contacts with the receptor. These
      results elucidate the mechanisms of molecular recognition of ligands by receptors
      of the low density lipoprotein receptor family.

PMID- 10085144
TI  - Regulation of intracellular ceramide content in B16 melanoma cells. Biological
      implications of ceramide glycosylation.
AB  - We previously reported that ceramide released from glycosphingolipids (GSLs) by
      endoglycoceramidase was directly metabolized to GSLs, and thus the content of
      GSLs was constantly maintained in B16 melanoma cells (Ito, M., and Komori, H.
      (1996) J. Biol. Chem. 271, 12655-12660). In this study, the metabolism of
      ceramide released from sphingomyelin (SM) by bacterial sphingomyelinase (SMase)
      was examined using B16 cells and their GSL-deficient mutant counterpart GM95
      cells. Treatment of B16 melanoma cells with bacterial SMase effectively
      hydrolyzed SM on the plasma membrane. Under these conditions,
      NeuAcalpha2,3Galbeta1, 4Glcbeta1,1ceramide was significantly increased.
      Interestingly, UDP-glucose:ceramide glucosyltransferase-1 (GlcT-1) activity and
      GSL synthesis, but not SM synthesis or sphingosine generation, were found to be
      up-regulated by SMase treatment. The up-regulation of GSL synthesis seemed to
      occur at both the transcriptional and post-translational steps of GlcT-1
      synthesis. Accumulation of ceramide by bacterial SMase was much higher in GM95
      cells than in the parental cells. When the enzyme was removed from the culture
      medium, the intracellular ceramide level in B16 cells, but not that in the mutant
      cells, normalized. No rapid restoration of SM in either of the cell lines was
      observed after removal of the enzyme. SMase treatment strongly inhibited DNA
      synthesis in GM95 cells but not that in B16 cells. In the presence of D-threo-1
      phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of GlcT-1, SMase
      treatment markedly increased the ceramide content and thus inhibited DNA
      synthesis in B16 cells. Our study provides the first evidence that GlcT-1
      functions to regulate the level of intracellular ceramide by glycosylation of the
      ceramide when it is present in excess.

PMID- 10085145
TI  - Recombinant human type II collagens with low and high levels of hydroxylysine and
      its glycosylated forms show marked differences in fibrillogenesis in vitro.
AB  - Type II collagen is the main structural component of hyaline cartilages where it
      forms networks of thin fibrils that differ in morphology from the much thicker
      fibrils of type I collagen. We studied here in vitro the formation of fibrils of
      pepsin-treated recombinant human type II collagen produced in insect cells. Two
      kinds of type II collagen preparation were used: low hydroxylysine collagen
      having 2.0 hydroxylysine residues/1,000 amino acids, including 1.3 glycosylated
      hydroxylysines; and high hydroxylysine collagen having 19 hydroxylysines/1,000
      amino acids, including 8.9 glycosylated hydroxylysines. A marked difference in
      fibril formation was found between these two kinds of collagen preparation, in
      that the maximal turbidity of the former was reached within 5 min under the
      standard assay conditions, whereas the absorbance of the latter increased until
      about 600 min. The critical concentration with the latter was about 10-fold, and
      the absorbance/microgram collagen incorporated into the fibrils was about one
      sixth. The morphology of the fibrils was also different, in that the high
      hydroxylysine collagen formed thin fibrils with essentially no interfibril
      interaction or aggregation, whereas the low hydroxylysine collagen formed thick
      fibrils on a background of thin ones. The data thus indicate that regulation of
      the extents of lysine hydroxylation and hydroxylysine glycosylation may play a
      major role in the regulation of collagen fibril formation and the morphology of
      the fibrils.

PMID- 10085146
TI  - SecA is required for the insertion of inner membrane proteins targeted by the
      Escherichia coli signal recognition particle.
AB  - Recent work has demonstrated that the signal recognition particle (SRP) is
      required for the efficient insertion of many proteins into the Escherichia coli
      inner membrane (IM). Based on an analogy to eukaryotic SRP, it is likely that
      bacterial SRP binds to inner membrane proteins (IMPs) co-translationally and then
      targets them to protein transport channels ("translocons"). Here we present
      evidence that SecA, which has previously been shown to facilitate the export of
      proteins targeted in a post-translational fashion, is also required for the
      membrane insertion of proteins targeted by SRP. The introduction of SecA
      mutations into strains that have modest SRP deficiencies produced a synthetic
      lethal effect, suggesting that SecA and SRP might function in the same
      biochemical pathway. Consistent with this explanation, depletion of SecA by
      inactivating a temperature-sensitive amber suppressor in a secAam strain
      completely blocked the membrane insertion of AcrB, a protein that is targeted by
      SRP. In the absence of substantial SecA, pulse-labeled AcrB was retained in the
      cytoplasm even after a prolonged chase period and was eventually degraded.
      Although protein export was also severely impaired by SecA depletion, the
      observation that more than 20% of the OmpA molecules were translocated properly
      showed that translocons were still active. Taken together, these results imply
      that SecA plays a much broader role in the transport of proteins across the E.
      coli IM than has been previously recognized.

PMID- 10085147
TI  - Nonvectorial surface transport, endocytosis via a Di-leucine-based motif, and
      bidirectional transcytosis of chimera encoding the cytosolic tail of rat FcRn
      expressed in Madin-Darby canine kidney cells.
AB  - Transfer of passive immunity from the mother to the fetus or newborn involves the
      transport of IgG across several epithelia. Depending on the species, IgG is
      transported prenatally across the placenta and yolk sac or is absorbed from
      colostrum and milk by the small intestine of the suckling newborn. In both cases
      apical to basolateral transepithelial transport of IgG is thought to be mediated
      by FcRn, an IgG Fc receptor with homology to major histocompatibility class I
      antigens. Here, we analyzed the intracellular routing of chimera encoding the rat
      FcRn tail fused to the ecto- and transmembrane domain of the macrophage
      FcgammaRIIb. Newly synthesized chimera were delivered in a nonvectorial manner to
      the apical and basolateral cell surface, from where the chimera were able to
      internalize and transcytose. Apical to basolateral and basolateral to apical
      transcytosis were differently regulated. This intracellular routing of the
      chimera is similar to that of the native FcRn, indicating that the cytosolic tail
      of the receptor is necessary and sufficient to endow an unrelated FcR with the
      intracellular transport behavior of FcRn. Furthermore, the di-leucine motif in
      the cytosolic domain of FcRn was required for rapid and efficient endocytosis but
      not for basolateral sorting of the chimera.

PMID- 10085148
TI  - Transcriptional activation of the glucose transporter GLUT1 in ventricular
      cardiac myocytes by hypertrophic agonists.
AB  - Myocardial hypertrophy is associated with increased basal glucose metabolism.
      Basal glucose transport into cardiac myocytes is mediated by the GLUT1 isoform of
      glucose transporters, whereas the GLUT4 isoform is responsible for regulatable
      glucose transport. Treatment of neonatal cardiac myocytes with the hypertrophic
      agonist 12-O-tetradecanoylphorbol-13-acetate or phenylephrine increased
      expression of Glut1 mRNA relative to Glut4 mRNA. To study the transcriptional
      regulation of GLUT1 expression, myocytes were transfected with luciferase
      reporter constructs under the control of the Glut1 promoter. Stimulation of the
      cells with 12-O-tetradecanoylphorbol-13-acetate or phenylephrine induced
      transcription from the Glut1 promoter, which was inhibited by cotransfection with
      the mitogen-activated protein kinase phosphatases CL100 and MKP-3. Cotransfection
      of the myocytes with constitutively active versions of Ras and MEK1 or an
      estrogen-inducible version of Raf1 also stimulated transcription from the Glut1
      promoter. Hypertrophic induction of the Glut1 promoter was also partially
      sensitive to inhibition of the phosphatidylinositol 3-kinase pathway and was
      strongly inhibited by cotransfection with dominant-negative Ras. Thus, Ras
      activation and pathways downstream of Ras mediate induction of the Glut1 promoter
      during myocardial hypertrophy.

PMID- 10085149
TI  - CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear
      factor-4 and enhances apolipoprotein gene expression.
AB  - Hepatocyte nuclear factor-4 (HNF-4) is a liver-enriched transcription factor that
      is crucial in the regulation of a large number of genes involved in glucose,
      cholesterol, and fatty acid metabolism and in determining the hepatic phenotype.
      We have previously shown that HNF-4 contains transcription activation functions
      at the N terminus (AF-1) and the C terminus (AF-2) which work synergistically to
      confer full HNF-4 activity. Here, we show that HNF-4 recruits the CREB-binding
      protein (CBP) coactivator on promoters of genes that contain functional HNF-4
      sites. HNF-4 interacts with the N-terminal region of CBP (amino acids 1-771) and
      the C-terminal region of CBP (amino acids 1812-2441). The two activating
      functions of HNF-4, AF-1 and AF-2, interact with the N terminus and the N and C
      terminus of CBP, respectively. In addition, we show that in contrast to the other
      nuclear hormone receptors the interaction between HNF-4 and CBP is ligand
      independent. Recruitment of CBP by HNF-4 results in an enhancement of the
      transcriptional activity of the latter. CBP does not activate gene expression in
      the absence of HNF-4, and dominant negative forms of HNF-4 prevent
      transcriptional activation by CBP, suggesting that the mere recruitment of CBP by
      HNF-4 is not sufficient for enhancement of gene expression. These findings
      demonstrate that CBP acts as a transcriptional coactivator for HNF-4 and provide
      new insights into the regulatory function of HNF-4.

PMID- 10085150
TI  - The hereditary hemochromatosis protein, HFE, specifically regulates transferrin
      mediated iron uptake in HeLa cells.
AB  - HFE is the protein product of the gene mutated in the autosomal recessive disease
      hereditary hemochromatosis (Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi,
      Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R. J., Ellis, M. C.,
      Fullan, A., Hinton, L. M., Jones, N. L., Kimmel, B. E., Kronmal, G. S., Lauer,
      P., Lee, V. K., Loeb, D. B., Mapa, F. A., McClelland, E., Meyer, N. C., Mintier,
      G. A., Moeller, N., Moore, T., Morikang, E., Prasss, C. E., Quintana, L.,
      Starnes, S. M., Schatzman, R. C., Brunke, K. J., Drayna, D. T., Risch, N. J.,
      Bacon, B. R., and Wolff, R. R. (1996) Nat. Genet. 13, 399-408). At the cell
      surface, HFE complexes with transferrin receptor (TfR), increasing the
      dissociation constant of transferrin (Tf) for its receptor 10-fold (Gross, C. N.,
      Irrinki, A., Feder, J. N., and Enns, C. A. (1998) J. Biol. Chem. 273, 22068
      22074; Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebron, J. A.,
      Watson, N. , Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., and Schatzman, R. C.
      (1998) Proc. Natl. Acad. Sci. U S A 95, 1472-1477). HFE does not remain at the
      cell surface, but traffics with TfR to Tf-positive internal compartments (Gross
      et al., 1998). Using a HeLa cell line in which the expression of HFE is
      controlled by tetracycline, we show that the expression of HFE reduces 55Fe
      uptake from Tf by 33% but does not affect the endocytic or exocytic rates of TfR
      cycling. Therefore, HFE appears to reduce cellular acquisition of iron from Tf
      within endocytic compartments. HFE specifically reduces iron uptake from Tf, as
      non-Tf-mediated iron uptake from Fe-nitrilotriacetic acid is not altered. These
      results explain the decreased ferritin levels seen in our HeLa cell system and
      demonstrate the specific control of HFE over the Tf-mediated pathway of iron
      uptake. These results also have implications for the understanding of cellular
      iron homeostasis in organs such as the liver, pancreas, heart, and spleen that
      are iron loaded in hereditary hemochromatotic individuals lacking functional HFE.

PMID- 10085151
TI  - Mutant vasopressin precursors that cause autosomal dominant neurohypophyseal
      diabetes insipidus retain dimerization and impair the secretion of wild-type
      proteins.
AB  - Autosomal dominant familial neurohypophyseal diabetes insipidus is caused by
      mutations in the arginine vasopressin (AVP) gene. We demonstrated recently that
      mutant AVP precursors accumulate within the endoplasmic reticulum of neuronal
      cells, leading to cellular toxicity. In this study, the possibility that mutant
      AVP precursors interact with wild-type (WT) proteins to alter their processing
      and function was explored. WT and mutant precursors were epitope-tagged to allow
      them to be distinguished in transfected cells. An in vivo cross-linking reaction
      revealed homo- and heterodimer formation between WT and mutant precursors. Mutant
      precursors were also shown to impair intracellular trafficking of WT precursors
      from the endoplasmic reticulum to the Golgi apparatus. In addition to the
      cytotoxicity caused by mutant AVP precursors, the interaction between the WT and
      mutant precursors suggests that a dominant-negative mechanism may also contribute
      to the pathogenesis of familial neurohypophyseal diabetes insipidus.

PMID- 10085152
TI  - Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric
      oxide. Implications for oxygen sensing and signaling.
AB  - It has been proposed that cells sense hypoxia by a heme protein, which transmits
      a signal that activates the heterodimeric transcription factor hypoxia-inducible
      factor 1 (HIF-1), thereby inducing a number of physiologically relevant genes
      such as erythropoietin (Epo). We have investigated the mechanism by which two
      heme-binding ligands, carbon monoxide and nitric oxide, affect oxygen sensing and
      signaling. Two concentrations of CO (10 and 80%) suppressed the activation of HIF
      1 and induction of Epo mRNA by hypoxia in a dose-dependent manner. In contrast,
      CO had no effect on the induction of HIF-1 activity and Epo expression by either
      cobalt chloride or the iron chelator desferrioxamine. The affinity of CO for the
      putative sensor was much lower than that of oxygen (Haldane coefficient,
      approximately 0.5). Parallel experiments were done with 100 microM sodium
      nitroprusside, a nitric oxide donor. Both NO and CO inhibited HIF-1 DNA binding
      by abrogating hypoxia-induced accumulation of HIF-1alpha protein. Moreover, both
      NO and CO specifically targeted the internal oxygen-dependent degradation domain
      of HIF-1alpha, and also repressed the C-terminal transactivation domain of HIF
      1alpha. Thus, NO and CO act proximally, presumably as heme ligands binding to the
      oxygen sensor, whereas desferrioxamine and perhaps cobalt appear to act at a site
      downstream.

PMID- 10085153
TI  - High mobility group-I(Y) protein facilitates nuclear factor-kappaB binding and
      transactivation of the inducible nitric-oxide synthase promoter/enhancer.
AB  - Nitric oxide (NO), a free radical gas whose production is catalyzed by the enzyme
      NO synthase, participates in the regulation of multiple organ systems. The
      inducible isoform of NO synthase (iNOS) is transcriptionally up-regulated by
      inflammatory stimuli; a critical mediator of this process is nuclear factor (NF)
      kappaB. Our objective was to determine which regulatory elements other than NF
      kappaB binding sites are important for activation of the iNOS promoter/enhancer.
      We also wanted to identify transcription factors that may be functioning in
      conjunction with NF-kappaB (subunits p50 and p65) to drive iNOS transcription.
      Deletion analysis of the iNOS promoter/enhancer revealed that an AT-rich sequence
      (-61 to -54) downstream of the NF-kappaB site (-85 to -76) in the 5'-flanking
      sequence was important for iNOS induction by interleukin-1beta and endotoxin in
      vascular smooth muscle cells. This AT-rich sequence, corresponding to an octamer
      (Oct) binding site, bound the architectural transcription factor high mobility
      group (HMG)-I(Y) protein. Electrophoretic mobility shift assays showed that HMG
      I(Y) and NF-kappaB subunit p50 bound to the iNOS promoter/enhancer to form a
      ternary complex. The formation of this complex required HMG-I(Y) binding at the
      Oct site. The location of an HMG-I(Y) binding site typically overlaps that of a
      recruited transcription factor. In the iNOS promoter/enhancer, however, HMG-I(Y)
      formed a complex with p50 while binding downstream of the NF-kappaB site.
      Furthermore, overexpression of HMG-I(Y) potentiated iNOS promoter/enhancer
      activity by p50 and p65 in transfection experiments, suggesting that HMG-I(Y)
      contributes to the transactivation of iNOS by NF-kappaB.

PMID- 10085154
TI  - Role of the cysteine-rich domain of the t-SNARE component, SYNDET, in membrane
      binding and subcellular localization.
AB  - Wild-type syndet is efficiently recruited at the plasma membrane in transfected
      AtT-20 cells. A deletion at the cysteine-rich domain abolishes palmitoylation,
      membrane binding, and plasma membrane distribution of syndet. Syndet, SNAP-25A,
      and SNAP-25B share four cysteine residues, of which three, Cys2, Cys4, and Cys5,
      are absolutely conserved in all three homologs. Mutations at any pair of
      cysteines within cysteines 2, 4, and 5 shift syndet from the cell surface into
      the cytoplasm. Thus, at least two cysteines within the conserved triplet are
      necessary for plasma membrane localization. Syndet C1S/C3S, with substitutions at
      the pair Cys1 and Cys3, distributes to the plasma membrane, a Golgi-like
      compartment, and the cytosol. We conclude that Cys1 and Cys3 are not absolutely
      necessary for membrane binding or plasma membrane localization. Our results show
      that the cysteine-rich domain of syndet plays a major role in its subcellular
      distribution.

PMID- 10085155
TI  - Differential effects of a calcineurin inhibitor on glutamate-induced
      phosphorylation of Ca2+/calmodulin-dependent protein kinases in cultured rat
      hippocampal neurons.
AB  - Calcium/calmodulin-dependent protein kinases (CaM kinases) are major
      multifunctional enzymes that play important roles in calcium-mediated signal
      transduction. To characterize their regulatory mechanisms in neurons, we compared
      glutamate-induced phosphorylation of CaM kinase IV and CaM kinase II in cultured
      rat hippocampal neurons. We observed that dephosphorylation of these kinases
      followed different time courses, suggesting different regulatory mechanisms for
      each kinase. Okadaic acid, an inhibitor of protein phosphatase (PP) 1 and PP2A,
      increased the phosphorylation of both kinases. In contrast, cyclosporin A, an
      inhibitor of calcineurin, showed different effects: the phosphorylation and
      activity of CaM kinase IV were significantly increased with this inhibitor, but
      those of CaM kinase II were not significantly increased. Cyclosporin A treatment
      of neurons increased phosphorylation of Thr196 of CaM kinase IV, the activated
      form with CaM kinase kinase, which was recognized with an anti-phospho-Thr196
      antibody. Moreover, recombinant CaM kinase IV was dephosphorylated and
      inactivated with calcineurin as well as with PP1, PP2A, and PP2C in vitro. These
      results suggest that CaM kinase IV, but not CaM kinase II, is directly regulated
      with calcineurin.

PMID- 10085156
TI  - Transmembrane topology of pmt1p, a member of an evolutionarily conserved family
      of protein O-mannosyltransferases.
AB  - The identification of the evolutionarily conserved family of dolichyl-phosphate-D
      mannose:protein O-mannosyltransferases (Pmts) revealed that protein O
      mannosylation plays an essential role in a number of physiologically important
      processes. Strikingly, all members of the Pmt protein family share almost
      identical hydropathy profiles; a central hydrophilic domain is flanked by amino-
      and carboxyl-terminal sequences containing several putative transmembrane
      helices. This pattern is of particular interest because it diverges from
      structural models of all glycosyltransferases characterized so far. Here, we
      examine the transmembrane topology of Pmt1p, an integral membrane protein of the
      endoplasmic reticulum, from Saccharomyces cerevisiae. Structural predictions were
      directly tested by site-directed mutagenesis of endogenous N-glycosylation sites,
      by fusing a topology-sensitive monitor protein domain to carboxyl-terminal
      truncated versions of the Pmt1 protein and, in addition, by N-glycosylation
      scanning. Based on our results we propose a seven-transmembrane helical model for
      the yeast Pmt1p mannosyltransferase. The Pmt1p amino terminus faces the
      cytoplasm, whereas the carboxyl terminus faces the lumen of the endoplasmic
      reticulum. A large hydrophilic segment that is oriented toward the lumen of the
      endoplasmic reticulum is flanked by five amino-terminal and two carboxyl-terminal
      membrane spanning domains. We could demonstrate that this central loop is
      essential for the function of Pmt1p.

PMID- 10085157
TI  - Two arylalkylamine N-acetyltransferase genes mediate melatonin synthesis in fish.
AB  - Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT, EC
      2.3.1.87) is the first enzyme in the conversion of serotonin to melatonin. Large
      changes in AANAT activity play an important role in the daily rhythms in
      melatonin production. Although a single AANAT gene has been found in mammals and
      the chicken, we have now identified two AANAT genes in fish. These genes are
      designated AANAT-1 and AANAT-2; all known AANATs belong to the AANAT-1 subfamily.
      Pike AANAT-1 is nearly exclusively expressed in the retina and AANAT-2 in the
      pineal gland. The abundance of each mRNA changes on a circadian basis, with
      retinal AANAT-1 mRNA peaking in late afternoon and pineal AANAT-2 mRNA peaking 6
      h later. The pike AANAT-1 and AANAT-2 enzymes (66% identical amino acids) exhibit
      marked differences in their affinity for serotonin, relative affinity for
      indoleethylamines versus phenylethylamines and temperature-activity
      relationships. Two AANAT genes also exist in another fish, the trout. The
      evolution of two AANATs may represent a strategy to optimally meet tissue-related
      requirements for synthesis of melatonin: pineal melatonin serves an endocrine
      role and retinal melatonin plays a paracrine role.

PMID- 10085158
TI  - Incorporation of Vpr into human immunodeficiency virus type 1 requires a direct
      interaction with the p6 domain of the p55 gag precursor.
AB  - The 96-amino acid Vpr protein is the major virion-associated accessory protein of
      the human immunodeficiency virus type 1 (HIV-1). As Vpr is not part of the p55
      Gag polyprotein precursor (Pr55(gag)), its incorporation requires an anchor to
      associate with the assembling viral particles. Although the molecular mechanism
      is presently unclear, the C-terminal region of the Pr55(gag) corresponding to the
      p6 domain appears to constitute such an anchor essential for the incorporation of
      the Vpr protein. In order to clarify the mechanism by which the Vpr accessory
      protein is trans-incorporated into progeny virion particles, we tested whether
      HIV-1 Vpr interacted with the Pr55(gag) using the yeast two-hybrid system and the
      maltose-binding protein pull-down assay. The present study provides genetic and
      biochemical evidence indicating that the Pr55(gag) can physically interact with
      the Vpr protein. Furthermore, point mutations affecting the integrity of the
      conserved L-X-S-L-F-G motif of p6(gag) completely abolish the interaction between
      Vpr and the Pr55(gag) and, as a consequence, prevent Vpr virion incorporation. In
      contrast to other studies, mutations affecting the integrity of the NCp7 zinc
      fingers impaired neither Vpr virion incorporation nor the binding between Vpr and
      the Pr55(gag). Conversely, amino acid substitutions in Vpr demonstrate that an
      intact N-terminal alpha-helical structure is essential for the Vpr-Pr55(gag)
      interaction. Vpr and the Pr55(gag) demonstrate a strong interaction in vitro as
      salt concentrations as high as 900 mM could not disrupt the interaction. Finally,
      the interaction is efficiently competed using anti-Vpr sera. Together, these
      results strongly suggest that Vpr trans-incorporation into HIV-1 particles
      requires a direct interaction between its N-terminal region and the C-terminal
      region of p6(gag). The development of Pr55(gag)-Vpr interaction assays may allow
      the screening of molecules that can prevent the incorporation of the Vpr
      accessory protein into HIV-1 virions, and thus inhibit its early functions.

PMID- 10085159
TI  - The Cdc6 protein is ubiquitinated in vivo for proteolysis in Saccharomyces
      cerevisiae.
AB  - The Saccharomyces cerevisiae Cdc6 protein is necessary for the formation of pre
      replicative complexes that are required for firing DNA replication at origins at
      the beginning of S phase. Cdc6p protein levels oscillate during the cell cycle.
      In a normal cell cycle the presence of this protein is restricted to G1, partly
      because the CDC6 gene is transcribed only during G1 and partly because the Cdc6p
      protein is rapidly degraded at late G1/early S phase. We report here that the
      Cdc6p protein is degraded in a Cdc4-dependent manner, suggesting that
      phosphorylated Cdc6 is specifically recognized by the ubiquitin-mediated
      proteolysis machinery. Indeed, we have found that Cdc6 is ubiquitinated in vivo
      and degraded by a Cdc4-dependent mechanism. Our data, together with previous
      observations regarding Cdc6 stability, suggest that under physiological
      conditions budding yeast cells degrade ubiquitinated Cdc6 every cell cycle at the
      beginning of S phase.

PMID- 10085160
TI  - PU.1 and USF are required for macrophage-specific mannose receptor promoter
      activity.
AB  - In the current study we report the isolation of 854 base pairs of the rat mannose
      receptor promoter. Analysis of the sequence revealed one Sp1 site, three PU.1
      sites, and a potential TATA box (TTTAAA) 33 base pairs 5' of the transcriptional
      start site. The tissue specificity of the promoter was determined using transient
      transfections. The promoter was most active in the mature macrophage cell line
      NR8383 although the promoter also showed activity in the monocytic cell line RAW.
      No activity was observed in pre-monocytic cell lines or epithelial cell lines.
      Mutation of the TTTAAA sequence to TTGGAA resulted in a 50% decrease in activity
      in transient transfection assays suggesting that the promoter contains a
      functional TATA box. Using electrophoretic mobility shift assays and mutagenesis
      we established that the transcription factors Sp1, PU.1, and USF bound to the
      mannose receptor promoter, but only PU.1 and USF contributed to activation.
      Transient transfections using a dominant negative construct of USF resulted in a
      50% decrease in mannose receptor promoter activity, further establishing the role
      of USF in activating the rat mannose receptor promoter. Comparison of the rat,
      mouse, and human sequence demonstrated that some binding sites are not conserved.
      Gel shifts were performed to investigate differences in protein binding between
      species. USF bound to the rat and human promoter but not to the mouse promoter,
      suggesting that different mechanisms are involved in regulation of mannose
      receptor expression in these species. From these results we conclude that,
      similar to other myeloid promoters, transcription of the rat mannose receptor is
      regulated by binding of PU.1 and a ubiquitous factor at an adjacent site.
      However, unlike other myeloid promoters, we have identified USF as the ubiquitous
      factor, and demonstrated that the promoter contains a functional TATA box.

PMID- 10085161
TI  - Nuclear retention of IkappaBalpha protects it from signal-induced degradation and
      inhibits nuclear factor kappaB transcriptional activation.
AB  - Transcriptional activation of nuclear factor kappaB (NF-kappaB) is mediated by
      signal-induced phosphorylation and degradation of its inhibitor, IkappaBalpha.
      However, NF-kappaB activation induces rapid resynthesis of IkappaBalpha, which is
      responsible for post-induction repression of transcription. Newly synthesized
      IkappaBalpha translocates to the nucleus, where it dissociates NF-kappaB from DNA
      and transports NF-kappaB from the nucleus to the cytoplasm in a nuclear export
      sequence-dependent process that is sensitive to leptomycin B (LMB). In the
      present study, LMB was used as a tool to inhibit nuclear export sequence-mediated
      nuclear protein export and evaluate the consequences for regulation of NF-kappaB
      dependent transcriptional activity. Pretreatment of cells with LMB inhibits NF
      kappaB-dependent transcriptional activation mediated by interleukin 1beta or
      tumor necrosis factor alpha. This is a consequence of the inhibition of signal
      induced degradation of IkappaBalpha. Although LMB treatment does not affect the
      signal transduction pathway leading to IkappaBalpha degradation, it blocks
      IkappaBalpha nuclear export. IkappaBalpha is thus accumulated in the nucleus, and
      in this compartment it is resistant to signal-induced degradation. These results
      indicate that the signal-induced degradation of IkappaBalpha is mainly, if not
      exclusively, a cytoplasmic process. An efficient nuclear export of IkappaBalpha
      is therefore essential for maintaining a low level of IkappaBalpha in the nucleus
      and allowing NF-kappaB to be transcriptionally active upon cell stimulation.

PMID- 10085162
TI  - Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of
      angiogenesis in vitro and in vivo.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that functions as a transcription factor to mediate ligand-dependent
      transcriptional regulation. Activation of PPARgamma by the naturally occurring
      ligand, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), or members of a new
      class of oral antidiabetic agents, e.g. BRL49653 and ciglitizone, has been linked
      to adipocyte differentiation, regulation of glucose homeostasis, inhibition of
      macrophage and monocyte activation, and inhibition of tumor cell proliferation.
      Here we report that human umbilical vein endothelial cells (HUVEC) express
      PPARgamma mRNA and protein. Activation of PPARgamma by the specific ligands 15d
      PGJ2, BRL49653, or ciglitizone, dose dependently suppresses HUVEC differentiation
      into tube-like structures in three-dimensional collagen gels. In contrast,
      specific PPARalpha and -beta ligands do not affect tube formation although mRNA
      for these receptors are expressed in HUVEC. PPARgamma ligands also inhibit the
      proliferative response of HUVEC to exogenous growth factors. Treatment of HUVEC
      with 15d-PGJ2 also reduced mRNA levels of vascular endothelial cell growth factor
      receptors 1 (Flt-1) and 2 (Flk/KDR) and urokinase plasminogen activator and
      increased plasminogen activator inhibitor-1 (PAI-1) mRNA. Finally, administration
      of 15d-PGJ2 inhibited vascular endothelial cell growth factor-induced
      angiogenesis in the rat cornea. These observations demonstrate that PPARgamma
      ligands are potent inhibitors of angiogenesis in vitro and in vivo, and suggest
      that PPARgamma may be an important molecular target for the development of small
      molecule inhibitors of angiogenesis.

PMID- 10085163
TI  - Role of protein kinase C in the translational regulation of lipoprotein lipase in
      adipocytes.
AB  - The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein
      lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is
      not known, elevated glucose is known to increase diacylglycerol, which activates
      protein kinase C (PKC). To determine whether PKC is involved in the regulation of
      LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on
      adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3
      F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity
      was observed after 6 h of treatment, and was observed at a concentration of 6 nM.
      100 nM TPA yielded maximal (80%) inhibition of LPL. No stimulation of LPL
      occurred after short term addition of TPA to cultures. To determine whether TPA
      treatment of adipocytes decreased LPL synthesis, cells were labeled with
      [35S]methionine and LPL protein was immunoprecipitated. LPL synthetic rate
      decreased after 6 h of TPA treatment. Western blot analysis of cell lysates
      indicated a decrease in LPL mass after TPA treatment. Despite this decrease in
      LPL synthesis, there was no change in LPL mRNA in the TPA-treated cells. Long
      term treatment of cells with TPA is known to down-regulate PKC. To assess the
      involvement of the different PKC isoforms, Western blotting was performed. TPA
      treatment of 3T3-F442A adipocytes decreased PKC alpha, beta, delta, and epsilon
      isoforms, whereas PKC lambda, theta, zeta, micro, iota, and gamma remained
      unchanged or decreased minimally. To directly assess the effect of PKC
      inhibition, PKC inhibitors (calphostin C and staurosporine) were added to
      cultures. The PKC inhibitors inhibited LPL activity rapidly (within 60 min).
      Thus, activation of PKC did not increase LPL, but inhibition of PKC resulted in
      decreased LPL synthesis by inhibition of translation, indicating a constitutive
      role of PKC in LPL gene expression.

PMID- 10085164
TI  - Polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran congener
      profiles in fish, crayfish, and sediment collected near a wood treating facility
      and a bleached kraft pulp mill.

PMID- 10085165
TI  - Acute toxicity bioassay using the freshwater luminescent bacterium Vibrio
      qinghaiensis sp. Nov.-Q67.

PMID- 10085166
TI  - Deltamethrin induced physiological changes in freshwater cat fish Heteropneustes
      fossilis.

PMID- 10085167
TI  - Parasitism, feeding rate, and hydrocarbon uptake of pink shrimp Pandalus borealis
      fed a crude oil contaminated diet.

PMID- 10085168
TI  - Sensitivity of the mysid Mysidopsis bahia to a weathered oils.

PMID- 10085169
TI  - Marine bacteria tolerant to chlorophenols.

PMID- 10085170
TI  - Determination of organochlorine pesticide residues in aquatic systems and
      organisms in upper Sakarya basin, Turkiye.

PMID- 10085171
TI  - Accumulation and loss of chromium by mussels (M. galloprovincialis).

PMID- 10085172
TI  - Trace metals in Lethrinus lentjan fish from the Arabian Gulf (Ras Al-Khaimah,
      United Arab Emirates): metal accumulation in kidney and heart tissues.

PMID- 10085173
TI  - Sequential extraction of copper, lead, cadmium, and zinc in sediments from Ebro
      river (Spain): relationship with levels detected in earthworms.

PMID- 10085174
TI  - Pesticides in homes in Western Australia.

PMID- 10085175
TI  - Reduction of norflurazon leaching in a sandy soil by adjuvants.

PMID- 10085176
TI  - Use of ozone to remove alachlor from surface water.

PMID- 10085177
TI  - Influence of dyeing and bleaching industries on ground water of Tirupur,
      Tamilnadu, India.

PMID- 10085178
TI  - Oxidation of 2-chlorophenol wastewater by hydrogen peroxide in the presence of
      basic oxygen furnace slag.

PMID- 10085179
TI  - Dissipation of phloxine B and uranine in protein bait sprayed in a coffee field
      for the suppression of Mediterranean fruit fly.

PMID- 10085180
TI  - Inhibition of 15-lipoxygenase by phthalate plasticizers.

PMID- 10085181
TI  - Teratogenicity of arecoline hydrobromide on developing chick embryos: a
      preliminary report.

PMID- 10085182
TI  - Developmental toxicity of triphenyltin chloride after administration on three
      consecutive days during organogenesis in rats.

PMID- 10085183
TI  - Influence of BHC and fenvalerate on mineralization and availability of some plant
      nutrients in soil.

PMID- 10085184
TI  - Introduction.

PMID- 10085185
TI  - Secondary Psychoses: An Overview.

PMID- 10085186
TI  - Psychosis Secondary to Encephalitis and Encephalopathies.
AB  - Psychosis due to encephalitis and encephalopathies is common and has been
      reported in multiple case reports or anecdotal observations. There are, however,
      few prospective studies or careful reviews summarizing this body of knowledge. In
      this review, we list a number of causes of psychosis that have been reported
      secondary to encephalitis and encephalopathies and focus in more detail on brain
      infections, inflammatory or demyelinating disease, temporal lobe epilepsy, and
      certain endocrine, metabolic, and nutritional deficiency states. Depending on the
      underlying etiology, the clinical features, course of illness, and treatment of
      these disturbances are quite variable. As systematic studies in these areas are
      lacking, there is a need for increased research to aid in the identification and
      management of psychotic conditions secondary to underlying encephalitis and
      encephalopathies.

PMID- 10085187
TI  - Psychosis Secondary to Brain Tumor.
AB  - Brain tumors may present with psychotic symptoms that resemble schizophrenia.
      Although psychosis secondary to brain tumor is relatively rare, the frequent lack
      of neurological findings can lead to misdiagnosis. Psychosis secondary to brain
      tumor is more common and also harder to accurately diagnose in the elderly. Key
      aspects of the epidemiology, clinical spectrum, diagnostic evaluation, and
      treatment are reviewed. The case of a 26-year old woman with psychosis secondary
      to a meningioma of the right lateral ventricle with extension into the corpus
      callosum and periventricular white matter is presented. Symptoms completely
      resolved after surgical excision of the tumor and remain in remission at 2(1/2)
      year follow-up on no medications. The clinician should maintain a high degree of
      vigilance for clinical features suggestive of this potentially reversible cause
      of psychosis.

PMID- 10085188
TI  - Posttraumatic Psychosis.
AB  - There are about three million cases of traumatic brain injury in the US each
      year. These patients have between two to five times greater risk of developing
      psychosis than the general population. In this report, we explore the limited
      number studies examining the incidence of psychosis in different populations.
      These studies were primarily retrospective and involved both veterans and
      civilians suffering from different types of injuries, penetrating or open and
      closed head injuries. Posttraumatic psychosis can occur several years after the
      head injury and the relationship between the injury and the psychosis is not
      always clear. In this report, we explore this relationship from the standpoint of
      risk factors for the development of psychosis. These may be lesion-specific such
      as the extent of the injury, laterality of lesion, as well as others such as
      genetic vulnerability and comorbid epilepsy, which actually may be an intervening
      variable between the brain injury and the onset of late-onset psychosis.
      Treatment is based on limited data and consists of both pharmacologic and
      nonpharmacologic approaches. Pharmacologic treatment of posttraumatic psychosis
      consists of symptomatic, functional, and hypothetical approaches. Specific
      pharmacologic treatment consists of antipsychotics, or antikindling
      anticonvulsants, or a combination thereof. Nonpharmacologic approaches such as
      cognitive retraining and behavioral treatment are oriented towards improving
      functioning and teaching adaptive coping strategies.

PMID- 10085189
TI  - Psychosis in Alzheimer's Disease.
AB  - The risk of psychotic symptoms in patients with Alzheimer's disease (AD) has been
      noted since the first case description of AD in 1907. Recent studies suggest that
      approximately a third of AD patients manifest psychosis at sometime during the
      course of their illness. Differentiating psychotic symptoms from the direct
      effects of cognitive dysfunction in AD can be challenging for clinicians and
      researchers. Nonetheless, the identification and treatment of such symptoms may
      be critical, as AD patients with psychosis may have a more rapid cognitive and
      functional decline, impose greater caregiver burden, and may be at increased risk
      of early institutionalization. Due to the potential side effects from neuroleptic
      medications, nonpharmacologic approaches to treatment should be considered,
      including environmental and behavioral modification and caregiver education. Some
      pharmacologic interventions may be necessary for symptoms not alleviated by these
      approaches, with specific elderly data for quetiapine and risperidone. Because
      there is no evidence for differential efficacy among the various neuroleptic
      medications, choice of an antipsychotic should be based on the side effect
      profiles of available medications weighed against the particular characteristics
      and situation of the individual patient.

PMID- 10085190
TI  - Psychoses in Parkinson's Disease.
AB  - Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD)
      and other degenerative parkinsonian disorders, usually but not exclusively in the
      context of their pharmacologic treatment. We describe the following six psychotic
      syndromes in PD based on existing literature: (1) hallucinations with preserved
      insight; (2) medication-induced psychotic disorders (in clear consciousness); (3)
      delirium; (4) schizophrenia-like psychotic disorders (in clear consciousness and
      in the absence of medication treatment); (5) schizophrenia with subsequent
      development of PD; and (6) other psychotic disorders. Psychosis in PD has been
      noted to be a marker for illness deterioration. Psychotic symptoms can profoundly
      affect the quality of life for PD patients and their families and may increase
      the economic burden of this illness. Various approaches have been used to treat
      psychotic symptoms in PD. We critically review this literature, which is limited,
      but includes studies indicating promise for "atypical" antipsychotics in these
      patients. Further elucidation of the phenomenology, course, pathophysiology, and
      treatment of the different psychotic disorders in PD is urgently needed.

PMID- 10085191
TI  - Psychosis in Dementia With Lewy Bodies.
AB  - Prominent psychotic symptoms, particularly hallucinations and delusions, have
      been estimated to occur in approximately 60% of patients with dementia with Lewy
      bodies (DLB). Many of these individuals experience psychotic symptoms before the
      onset of other features characteristic of DLB. To facilitate consistent diagnosis
      of DLB, an international consortium recently created consensus guidelines for the
      clinical and pathological diagnosis of this disease. Accurate diagnosis of DLB is
      particularly important as these patients may have greater neuroleptic sensitivity
      than other elderly patients. Currently there is no verified treatment
      specifically for psychotic symptoms in DLB. However, if neuroleptic treatment
      cannot be avoided, low doses of atypical antipsychotics may prove beneficial,
      while minimizing anticholinergic and extrapyramidal side effects.

PMID- 10085192
TI  - Iatrogenic Psychoses.
AB  - Iatrogenic psychoses can cause disability, worsen previous disability, and render
      clinical management extraordinarily difficult. In certain cases, psychosis
      precedes more severe and overt toxicity, which can lead to encephalopathy or
      coma. This article offers an overview of iatrogenic (ie, treatment-induced)
      psychoses. "Pure" psychoses (ie, without confusion or mood disturbance) are
      emphasized. Shortcomings of available data are highlighted. The epidemiology,
      definition, diagnosis, differential diagnoses, risk factors, and course are
      discussed. Therapeutic measures include discontinuation or decreasing the dose of
      the suspected medication and the administration of neuroleptics, antimanics, and
      antidepressants. Other general principles of clinical management are given. A
      brief review of etiopathogenic mechanisms is offered and areas for future
      research are emphasized.

PMID- 10085193
TI  - Substance-Induced Psychosis.
AB  - Intoxication and withdrawal from a variety of central nervous system depressants
      and stimulants may induce hallucinations or delusions, which, when unaccompanied
      by insight, are the hallmarks of psychosis. A substance-induced psychosis may, in
      many instances, present as an organic psychosis or as an independent mental
      disorder (eg, schizophrenia), complicating diagnostic efforts. Ramifications of a
      misdiagnosed psychotic illness are potentially long-lasting and harmful to a
      patient. It is, therefore, crucial that health care providers be aware of the
      complex relationship between substance abuse, psychotic symptoms, and independent
      psychotic disorders. This report addresses substance-induced psychosis, by
      describing those psychotic symptoms most commonly associated with the abuse of
      specific drugs and alcohol, detailing useful diagnostic techniques and outlining
      treatment recommendations.

PMID- 10085195
TI  - The Effect of Major Depression on Chronic Medical Illness.

PMID- 10085194
TI  - Introduction.

PMID- 10085196
TI  - Major Depression and Heart Disease: Treatment Trials.
AB  - Cardiac disease and depression affect a significant number of individuals every
      year, and developing effective treatment for depression in cardiac disease could
      have a substantial impact on public health. Several studies have shown that
      depression increases cardiac morbidity and mortality and total costs of care and
      is associated with a poor psychosocial outcome. Psychopharmacological treatment
      trials have shown that tricyclic antidepressants have antiarrhythmic effects,
      prolong cardiac conduction, and cause orthostatic hypotension, but do not impair
      left ventricular function, even in patients with underlying left ventricular
      impairment. Tricyclic antidepressants are efficacious in treating depression but
      have a higher rate of cardiovascular complications than other antidepressants,
      with orthostatic hypotension being the most common complication. Recent small
      clinical trials with bupropion and selective serotonin reuptake inhibitors
      (SSRIs) indicate that they are efficacious and have a more benign cardiovascular
      side-effect profile, although large studies need to be performed to establish
      their safety and efficacy. Most psychosocial studies have focused on cardiac
      patients in general and not specifically on depressed cardiac patients. Studies
      of cardiac patients have shown that stress, social isolation, and lower income
      and educational levels are associated with a poorer cardiac outcome. A large meta
      analysis of randomized, controlled trials of psychosocial interventions in
      nondepressed cardiac patients found that a diverse array of psychosocial
      interventions decreased morbidity and mortality. However, one recent psychosocial
      treatment trial of post-myocardial infarction (MI) patients has shown increased
      mortality in women in the intervention arm of the trial. There have been several
      recent studies showing that mental stress induces cardiac ischemia, that mental
      stress-induced cardiac ischemia is associated with a higher rate of adverse
      cardiac events than exercise-induced ischemia, and that with stress management
      training, patients show significant reductions in ischemic responses to mental
      stress. Currently, there are two large studies underway examining pharmacological
      and psychotherapeutic treatment of post-MI depressed and/or socially isolated
      patients. These large clinical trials are needed to determine if effective
      treatment of depression can modify the increased risk for mortality and morbidity
      associated with depression in cardiac disease. Hopefully, the development of
      effective treatment for depressed cardiac patients will decrease their morbidity
      and mortality and enhance their overall quality and enjoyment of life.

PMID- 10085197
TI  - Management of Major Depression in Adults With Diabetes: Implications of Recent
      Clinical Trials.
AB  - Major depressive disorder is present in 15%-20% of patients with diabetes and
      impairs functioning and quality of life. It has unique importance in diabetes
      because of its association with poor compliance with diabetes treatment, poor
      glycemic control, and an increased risk for micro- and macrovascular disease
      complications. These observations have inspired several recent clinical trials to
      determine whether these associations may be favorably influenced by depression
      treatment. The outcome data are scant but promising and suggest that
      psychotherapy and pharmacotherapy can have important positive effects on both
      mood and glycemic control. Unfortunately, even after successful treatment,
      recurrence of depression is the norm. Afflicted subjects are seldom asymptomatic
      for an entire year at a time. Factors related to the medical illness (eg,
      presence of diabetes complications, hyperglycemia) are associated with a poorer
      prognosis for recovery from depression, a finding that suggests that optimal
      relief of depression in diabetes may require vigorous, simultaneous management of
      the medical and psychiatric conditions. Whether maintenance antidepressant
      treatment is useful in preventing depression recurrence and promoting better
      glycemic control in diabetes is unknown, but this question is the focus of an
      ongoing clinical trial.

PMID- 10085198
TI  - Depression and Chronic Obstructive Pulmonary Disease: Treatment Trials.
AB  - Chronic obstructive pulmonary disease (COPD) affects over 16 million people in
      the United States and is a major cause of disability and death worldwide. Its
      prevalence and mortality are increasing disproportionately among the elderly,
      women, African-Americans, persons of lower socioeconomic status, and the
      populations of developing countries in which tobacco is aggressively marketed. In
      contrast to other major chronic diseases such as heart disease and cancer,
      medical treatments for COPD have not made decisive inroads into its morbidity or
      death rates over the last 20 years, resulting in continuing efforts to reduce
      disability in patients with established disease. Depression is a source of
      increased disability in COPD, and, as in other chronically ill patient
      populations, is often unrecognized and untreated in the primary and specialty
      care sectors. Nearly half of all patients experience some depressive symptoms and
      at least one-fifth have had one or more major depressive episodes, frequently of
      long duration. Evidence from randomized controlled trials supports the thesis
      that patients with mild depression improve with multidisciplinary rehabilitation,
      whereas patients with major depression may require specific pharmacotherapy to
      achieve significant improvement in mood disorder and day-to-day function. In
      addition to its impact on disability, depression may contribute indirectly to the
      etiology and progression of COPD through its relationship to addictive smoking.
      Mood disorder in adolescence and early adulthood contributes to early smoking and
      failure to quit, even after the onset of respiratory disease in later life.
      Patients with a history of major depression are more likely to fail in smoking
      cessation programs and to develop a major depressive episode when they do stop.
      This relationship calls for psychiatrically informed intervention models to
      improve long-term abstinence rates. The functional impairments associated with
      COPD are themselves potential promoters of depressive morbidity and chronicity,
      acting through complex causal pathways. Progressive hypoxia due to respiratory
      insufficiency leads to structural brain changes and neurocognitive deficits that
      impair day-to-day function and reduce adaptive potential; and oxygen therapy, as
      now practiced, offers minimal neurocognitive and mood benefits to most patients.
      Limited data from studies of experimental hypoxia in animals suggest that
      relatively mild lack of oxygen impairs the function and plasticity of critical
      neurotransmitter systems implicated in both cognition and mood, although current
      practice standards withhold oxygen therapy until late in the course of disease
      when the damaging effects of hypoxia on the brain have become well established.
      Neuropsychiatric approaches to the prevention, delay, and treatment of brain
      dysfunction should be a primary objective of research to improve patient
      outcomes. A comprehensive relational model that links pulmonary disease, hypoxia,
      neurocognitive impairment, and structural brain disease with depression provides
      a useful framework for the design of such studies. The near-term research agenda
      should include three components: (1) practical methods for improving physician
      and patient recognition of depression and neurocognitive impairment as targets
      for intervention; (2) additional trials of standard antidepressant treatment
      approaches for both major and minor depression; and (3) tests of the hypothesis
      that late-onset depression in patients with COPD is a marker for the presence of
      neurocognitive deficits and structural brain changes. The long-range research
      agenda must aim at preventive interventions designed to forestall brain
      deterioration. Controlled clinical trials of supplemental oxygen in patients with
      mild hypoxia and minimal cognitive deficits are needed to determine whether early
      treatment can reverse or moderate decline, reduce the incidence and chronicity of
      depression, and improve response to antidepressant treatment. Novel
      neuroprotective therapies such as antioxidant supplementation and modulation of
      monoaminergic neurotransmission, coupled with overall improvements in long-term
      respiratory disease management that minimize episodes of increased systemic
      oxidative stress, should be considered for multisite trials designed to define
      optimal treatment and prevention.

PMID- 10085199
TI  - Treatment of Depression in Individuals With Cancer: Implications of
      Antidepressant Pharmacotherapy.
AB  - Depression is frequently underdiagnosed and inadequately treated in individuals
      with cancer. A number of factors render cancer patients more vulnerable to
      depression. These include variables such as metabolic and endocrine alteration,
      chemotherapeutic and immune modifiers used to treat the cancer, steroids, and
      uncontrolled pain. Surprisingly, few controlled studies have examined the
      efficacy of antidepressant medications in depressed cancer patients. This report
      summarizes the available antidepressant medication treatment trials, the results
      of which suggest that antidepressant therapy can alleviate depression and improve
      quality of life in depressed individuals with cancer. Theoretical as well as
      practical issues guiding current research and pharmacotherapeutic treatment
      decisions are also discussed.

PMID- 10085200
TI  - Major Depressive Disorder and HIV-1 Infection: A Review of Treatment Trials.
AB  - Major depression is a common psychiatric presentation during the course of many
      chronic illnesses. Although estimates of its prevalence in people with human
      immunodeficiency virus (HIV) infection and acquired immunedeficiency syndrome
      have varied widely in the literature, it has become increasingly clear that
      people with HIV infection experience depression or depressive symptoms
      frequently, and that major depression may be the most common psychiatric
      disorder. This report reviewed the currently reported data and clinical trials
      for treatment of depression or depressive symptoms in the course of HIV
      infection. We have reviewed both psychopharmacologic and psychotherapy trials and
      although blinded efficacy studies are the gold standard, because there is often a
      lack of data, we have included noncontrolled (open) trials for comparison.
      Pharmacologic medication trials show that selective serotonin reuptake inhibitors
      (SSRIs), although not more efficacious, may be more tolerable and have greater
      overall effectiveness. Furthermore, when medications are used to treat
      depression, it may be essential to evaluate for tolerability and potential drug
      interactions to increase efficacy. Psychotherapy trials have investigated a
      variety of treatment modalities including group, individual, and stress reduction
      techniques. In treatment trials, all of these modalities have been associated
      with a reduction in distress and depressive symptoms. With the advances in
      therapy for HIV infection, treatment of a major depressive episode or depressive
      symptoms has become increasing important because untreated depression could both
      compromise medication adherence and potentiate the disabling effects of the
      illness.

PMID- 10085202
TI  - Introduction.

PMID- 10085201
TI  - Treatment of Depression at the End of Life: Clinical and Ethical Issues.
AB  - The issue of "treatable depression" in terminally ill patients has been raised in
      discussions of physician-assisted suicide. However, the role of psychiatry in
      palliative care remains largely undefined. Studies have documented a major
      depression prevalence in hospitalized patients with acquired immunodeficiency
      syndrome (AIDS) and cancer of 17% to 36% and in terminally ill patients from 9%
      to 17%. No randomized, controlled trials of depression treatment in the
      terminally ill have been completed. Tricyclic antidepressants and selective
      sertonin reuptake inhibitors (SSRIs) have been proven effective in randomized
      trials for major depression in patients with cancer or human immunodeficiency
      virus (HIV) infection. Psychostimulants have shown effectiveness by randomized
      trial in medical inpatients, but only by case series in the terminally ill.
      Randomized trials have shown the effectiveness of psychotherapies for depression
      in cancer (ie, cognitive behavioral) and HIV-infected patients (ie,
      interpersonal). An open trial suggests effectiveness for problem-solving therapy
      for terminally ill patients. In summary, the treatability of depression in the
      terminally ill remains to be proven by randomized trials.

PMID- 10085203
TI  - Traumatic Brain Injury: A Model of Acquired Psychiatric Illness?

PMID- 10085204
TI  - Neuropathology of the Head Injuries.
AB  - Structural abnormalities develop progressively after trauma to the central
      nervous system suggesting that injury is a process of events rather than a
      singular event. Thus, numerous types of neuropathologies can occur, depending on
      the exact nature of the processes of cellular damage that are set into motion
      after injury. Four general interrelated processes of delayed cellular damage
      occur in different amounts and in different locations to result in the numerous
      types of traumatic brain damage. These include direct damage caused by calcium
      influx into cells, free radical-mediated damage, receptor-mediated damage, and
      inflammation. By these mechanisms, the general response of the brain to
      mechanical energy causes damage to vascular or neural components of the brain,
      and results in principally focal or diffuse brain damage, respectively. These
      form the phenotypic types of damage to the brain and the resulting clinically
      associated traumatic syndromes. Focal brain damage consists principally of
      vascular injury that results in confusions and hemorrhages in various locations.
      Diffuse brain damage mainly involves scattered damage to axons in the white
      matter (diffuse axonal injury) or secondary damage attributable to raised
      intracranial pressure, hypoxia, or ischemia.

PMID- 10085205
TI  - Secondary Injury After Head Trauma: Subacute and Long-term Mechanisms.
AB  - Mechanisms of the secondary injuries associated with traumatic brain injury, and
      their long-term effects on behavior and on the possible development of
      neurodegenerative disease, represent major opportunities to understand the
      brain's efforts at self-repair. A multiplicity of endogenous factors and genetic
      predispositions interact to affect outcomes. More pragmatically, the elucidation
      of such mechanisms offer multiple opportunities to intervene therapeutically.

PMID- 10085206
TI  - Frontal Lobe Dysfunction in Traumatic Brain Injury.
AB  - The frontal lobes are responsible for many higher cognitive abilities, including
      executive, inhibitory, and motivational functions. The frontal lobes are
      particularly prone to damage in closed head injury because of direct contusion,
      as well as disruption of connections on which frontal systems depend for
      functioning. Three primary behavioral syndromes are described, associated with
      damage to dorsolateral, orbital, and mesial frontal subsystems. Two approaches to
      rehabilitation of frontal dysfunction are reviewed.

PMID- 10085207
TI  - Regulation of Affect.
AB  - Pathological crying is a frequent consequence of traumatic brain injury, and can
      easily be misconstrued as a symptom of major depressive disorder or an adjustment
      problem. First, this article discusses the neurobiological bases of pathological
      crying. The multiplicity of pathological entities and lesion locations that can
      produce this pathological affect are highlighted. The literature is reviewed with
      respect to the occurrence of pathological crying, specifically in traumatic brain
      injury. Consideration is then given to the clinical assessment of patients where
      crying is the chief complaint, and the traditional differential diagnostic
      approach is emphasized. Finally, psychological and somatic treatment
      considerations are addressed. Although psychopharmacological intervention can
      often provide significant relief, patient and family education about this
      clinical phenomenon is essential.

PMID- 10085208
TI  - Lack of Awareness of Deficits in Traumatic Brain Injury.
AB  - Lack of awareness of deficits is often seen in neurological and psychiatric
      disorders. Clues to the etiology of awareness deficits in these disorders can
      increase our understanding of the lack of awareness in traumatic brain injury
      (TBI). Research suggests that up to 45% of individuals with moderate to severe
      TBI have reduced awareness or complete lack of awareness of their deficits. The
      authors describe dimemsions and distinctions within the concept of lack of
      awareness-including whether an individual has knowledge of a specific deficit,
      the emotional response an individual manifests to a specific deficit, the ability
      to comprehend the impact or consequences of the deficit on day-to-day life, and
      how an individual explains or accounts for any deficits-and suggest that these
      discriminations have clinical, research, and theoretical value. These different
      aspects of lack of awareness have distinct neurological underpinnings as well as
      important treatment implications.

PMID- 10085209
TI  - Traumatic Brain Injury and Psychosis: What Is the Connection?
AB  - Psychotic syndromes occur more frequently in individuals who have had a traumatic
      brain injury (TBI) than in the general population. Psychotic syndromes following
      a TBI can present in the period of post-traumatic anmesia, in association with
      post-traumatic epilepsy, in association with TBI-related mood disorders, and as a
      chronic, schizophrenia-like syndrome. Individuals with schizophrenia (a chronic
      psychotic disorder) have a higher frequency of prior TBI than individuals with
      other psychiatric disorders. These observations suggest an intriguing link
      between psychosis and TBI. The study of the neuroanatomical and neuropathological
      substrate of schizophrenia, and of the core symptoms of the disorder ("negative"
      symptoms, hallucinations, delusions), suggests that abnormalities in the
      structure and function of certain brain regions play a role in the genesis and
      maintenance of these core symptoms. The key brain regions include the
      dorsolateral prefrontal cortex, temporal lobe structures, basal ganglia,
      thalamus, and cingulate gyrus. These brain regions are commonly injured in many
      patients with TBI, suggesting a possible mechanism underlying the observed link
      between TBI and psychosis. This article reviews the literature on TBI and
      psychosis, and suggests an approach to the evaluation and treatment of
      individuals with TBI and psychosis.

PMID- 10085210
TI  - Disorders of Mood After Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) of any severity can result in broad and persisting
      biopsychosocial sequelae. Post-TBI sequelae impact, to varying degrees, a
      person's ability to function at home and work, leading to added emotional
      distress. It is in the context of these biological, interpersonal, and social
      disruptions that mood disorders can arise. Mood disorders after TBI occur at a
      greater frequency than in the general population, with estimates approaching 25%
      to 50% for major depression, 15% to 30% for dysthymia, and 9% for mania. Post-TBI
      depression and mania appear to embrace a symptom presentation that is similar to
      non-TBI depression and mania, and the symptoms can be discerned from other
      neurobehavioral symptoms. TBI-related brain damage consistently involves regions
      of the brain that are increasingly recognized as important in the regulation of
      mood, including the frontal cortex, basal ganglia, and temporal lobes. However,
      there is insufficient information to postulate a specific neuroanatomic model for
      post-TBI depression and mania. It is the variable nature of TBI-related brain
      injury, occurring in the context of other relevant factors that limit the ability
      to make accurate models to predict who will develop a post-TBI mood disorder.

PMID- 10085211
TI  - Modulation of Anger and Aggression.
AB  - Traumatic brain injury commonly results in anger and aggressive behavior. The
      hypothalamus, limbic system, and prefrontal cortex mediate aggression, and
      frequently are injured during trauma. Many neurotransmitters that modulate
      aggressive behavior, including norepinephrine, serotonin, dopamine, and
      acetylcholine are affected by brain injury. The pharmacological treatment of
      aggression is divided into medications used for acute behavioral control, and
      those used for the prophylaxis of episodes. Specific recommendations are made for
      the choice of specific medications.

PMID- 10085212
TI  - Introduction.

PMID- 10085213
TI  - Biological and Environmental Factors in the Development of Early Psychopathology.

PMID- 10085214
TI  - The Importance of Brain Development for Understanding Early-Onset Psychiatric
      Disorders.
AB  - Developmental brain pathology is a risk factor for early-onset psychopathology.
      This article provides an overview of the contributions from the developmental
      neurosciences to our understanding of early-onset psychopathology. It reviews
      normal human brain development, the role of clinical observation to the
      development of animal models of early-onset psychopathology and, finally,
      corroborative studies in humans based upon findings from the animal experiments.
      These models permit study, at the mechanistic level, as to how a specific
      neurochemical lesion in a specific anatomic area at a specific developmental
      stage results in a characteristic behavioral phenotype. The models provide new
      insights into the concept of a critical period whether they are the result of the
      transient, developmental expression of a gene or whether they result from the
      unique anatomy of the brain at a particular age or stage. Animal models of early
      onset psychopathology provide important insights into the potential neuroanatomic
      substrates and developmental processes that are relevant to the emergence of a
      particular disorder. Ultimately, their study will lead to a generation of
      therapeutic tools to effectively address the actual disease process. More
      importantly, they are the first step in developing preventive interventions for
      early-onset, severe psychopathology. Thus, their value to advancing our
      understanding of these clinical conditions is inestimable.

PMID- 10085215
TI  - Development and Psychopathology: Fetal Alcohol Syndrome and Related Conditions.
AB  - Prenatal exposure to alcohol, which is a neurobehavioral teratogen, can cause
      defects in the structure and function of the developing central nervous system
      and can also impact growth and morphology. These wide-ranging effects occur along
      a continuum, with the most severe impact known as fetal alcohol syndrome (FAS).
      As the identified population of alcohol-affected patients grows, because of
      enhanced societal awareness and increased diagnostic capability, it has become
      clear that the continuum of fetal alcohol effects can mean lifelong disabilities
      with serious implications for function in adolescence and adulthood. Both
      "primary" cognitive, communication, and behavioral difficulties, and adverse life
      outcomes or "secondary" disabilities occur. Caregivers report that alcohol
      affected patients present an array of mental health concerns, suggesting that
      these patients will be seen in clinical practice. This review presents current
      information on diagnosis and incidence and overviews evidence that shows central
      nervous system dysfunction in this patient population. The basis for alcohol
      effects, and developmental influences on the expression of these effects, are
      discussed. Recent data on secondary disabilities and psychiatric conditions are
      provided, and clinical practice issues are discussed in detail, including
      conceptualizations of how secondary disabilities emerge, the diagnostic process,
      assessment, and intervention strategies.

PMID- 10085216
TI  - The Effects of Early Social Relationships on Neurotransmitter Development and the
      Vulnerability to Affective Disorders.
AB  - Recent evidence has shown that early exposure to stressful stimuli in the
      environment can impact the monoaminergic neurotransmitter systems, the structural
      development of the brain, and alter gene expression. In this article, we review
      data from animal studies, nonhuman primate studies, and human studies, which
      illustrate that environmental factors can influence brain chemistry and behavior.
      One important early social interaction is the mother-infant dyad. The nature of
      the infant-mother relationship appears to be important to exacerbating a
      potential vulnerability to affective disorders. Severe neglect, neglectful and/or
      emotionless parenting appears to have specific and long lasting biochemical and
      behavioral consequences. The exact interplay of genetic and environmental factors
      in affective disorders is unknown; however, we propose a model in which exposure
      to early adverse stimuli in an affective disorder susceptible or nonsusceptible
      individual during the first 3 years of life can alter gene expression leading to
      an increase of affective disorders.

PMID- 10085217
TI  - Early-Onset Oppositional Defiant Disorder: What Factors Predict Its Course?
AB  - Although the early onset of Oppositional Defiant Disorder (ODD) is associated
      with an elevated risk of later psychopathology (including but not limited to
      conduct disorder and antisocial personality disorder), little is known about the
      factors influencing the course of this disorder in early life. In this article we
      first review data and theory from four conceptually-distinct domains of risk
      factors for disruptive disorders (child characteristics reflecting biologic
      vulnerabilities, parent-child attachment, parenting practices, and family
      adversity). Then we describe an empirical study that examined the power of these
      four domains (representing 10 specific risk factors) to predict the prognosis of
      clinic-referred, preschool boys with ODD; risk factors were assessed when these
      youngsters were first evaluated in the clinic and outcomes were measured 2 years
      later. The primary goal was to determine the unique importance of risk factors in
      the context of others examined simultaneously, a strategy that few previous
      studies have used. We found that the four-factor risk model predicted significant
      variance in mother's reports of externalizing (disruptive) behavior problems at
      the 2-year follow-up; however, the model did not predict teacher externalizing
      scores or clinicians' assessments of Diagnostic and Statistical Manual (DSM)
      disorders, as hypothesized. Analyses of specific factors within domains suggested
      that three were most consistently related to the negative outcomes of ODD boys:
      greater use of physical discipline by parents, greater life stress for families,
      and a greater number of pre- and perinatal complications. Nearly a third of the
      variance in mothers' reports of internalizing (inhibited) problems was
      attributable to two of these risk factors (life events stress and birth history)
      and to a third factor, delayed child development.

PMID- 10085218
TI  - Neurodevelopmental Pathways in Schizophrenia.
AB  - We examined early-onset schizophrenia as a neurodevelopmental disorder. These
      data are from a 2-year longitudinal prospective study of youth with psychotic
      disorders. Standardized diagnostic and neuropsychological assessments include:
      Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV;
      Diagnostic Interview for Children and Adolescents, Revised; Premorbid Adjustment
      Scale; Wechsler Intelligence Scale for Children-III; the Wisconsin Card Sorting
      Test (WCST), and the California Verbal Learning Test. Pertinent family and
      developmental history are obtained via parent interviews and chart review. Forty
      eight subjects have been recruited to date; 17 with schizophrenia, 13 with
      bipolar disorder, 10 with psychosis nos, seven with schizoaffective disorder, and
      one with an organic psychosis. Subjects with schizophrenia had higher ratings of
      premorbid social withdrawal and dysfunctional peer relationships. All groups had
      high rates of cognitive impairment, prenatal/perinatal complications, and
      comorbid psychiatric disorders. Homotypic family psychiatric history was
      associated with diagnosis in youth. Our data are consistent with a
      neurodevelopmental model, whereby specific genetic/neurological risk factors and
      nonspecific biologic/environmental modulating factors interact in the development
      of schizophrenia and other psychotic disorders.

PMID- 10085219
TI  - Developmental Psychopathology Courts Developmental Neurobiology: Current Issues
      and Future Challenges.
AB  - The last decade has witnessed significant advances in theory and research in the
      fields of developmental psychopathology and developmental neurobiology. These two
      fields have much in common, sharing a number of guiding principles and
      assumptions. This article describes the research implications that these shared
      principles contain for the growing partnership between developmental
      psychopathology and developmental neurobiology. Based upon the methods
      successfully employed in the developmental neurosciences, the author emphasizes
      that developmental psychopathology must (A) construct more specific (even clever)
      research questions, (B) develop research tools more capable of examining time
      dependent brain-behavior relations, (C) outline and test particular causal
      mechanisms and their contextual dependencies, and (D) avoid formulaic,
      nonthinking statistics and design methods that often characterize mental health
      research.

PMID- 10085221
TI  - Gi-mediated tyrosine phosphorylation of Grb2 (growth-factor-receptor-bound
      protein 2)-bound dynamin-II by lysophosphatidic acid.
AB  - Lysophosphatidic acid (LPA) is the prototypic G-protein-coupled receptor agonist
      that activates the Ras-mitogen-activated protein (MAP) kinase cascade through
      pertussis toxin (PTX)-sensitive Gi and enhanced tyrosine kinase activity. We
      recently detected a 100 kDa protein (p100) that binds to the C-terminal SH3
      domain of growth-factor-receptor-bound protein 2 (Grb2) and becomes tyrosine
      phosphorylated in a PTX-sensitive manner in LPA-treated Rat-1 cells [Kranenburg,
      Verlaan, Hordijk and Moolenaar (1997) EMBO J. 16, 3097-3105]. Through glutathione
      S-transferase-Grb2 affinity purification and microsequencing, we have now
      identified p100 as dynamin-II, a GTPase that regulates clathrin-mediated
      endocytosis. We show that in Rat-1 cells, Grb2-bound dynamin-II is rapidly
      tyrosine phosphorylated in response to LPA in a PTX-sensitive manner. Thus,
      tyrosine phosphorylation of Grb2-bound dynamin-II may be a critical event in Gi
      mediated activation of the Ras-MAP kinase cascade in fibroblasts.

PMID- 10085220
TI  - The protein disulphide-isomerase family: unravelling a string of folds.
AB  - The mammalian protein disulphide-isomerase (PDI) family encompasses several
      highly divergent proteins that are involved in the processing and maturation of
      secretory proteins in the endoplasmic reticulum. These proteins are characterized
      by the presence of one or more domains of roughly 95-110 amino acids related to
      the cytoplasmic protein thioredoxin. All but the PDI-D subfamily are composed
      entirely of repeats of such domains, with at least one domain containing and one
      domain lacking a redox-active -Cys-Xaa-Xaa-Cys- tetrapeptide. In addition to
      their known roles as redox catalysts and isomerases, the last few years have
      revealed additional functions of the PDI proteins, including peptide binding,
      cell adhesion and perhaps chaperone activities. Attention is now turning to the
      non-redox-active domains of the PDIs, which may play an important role in all of
      the known activities of these proteins. Thus the presence of both redox-active
      and -inactive domains within these proteins portends a complexity of functions
      differentially accommodated by the various family members.

PMID- 10085222
TI  - Identification of a Leu-lle internalization motif within the cytoplasmic domain
      of the leukaemia inhibitory factor receptor.
AB  - Leukaemia inhibitory factor (LIF) signals via a heterodimeric receptor complex
      comprised of the LIF receptor (LIFR) and the interleukin (IL)-6 signal transducer
      gp130. Upon binding to its cognate receptor LIF is internalized. In this study,
      we show that the LIFR is endocytosed independently of gp130. By using a
      heterochimaeric receptor system we identified a dileucine-based internalization
      motif within the cytoplasmic domain of the LIFR. Our findings suggest that a
      heterodimeric LIFR/gp130 complex and homodimeric gp130/gp130 complex are
      endocytosed via distinct internalization signals.

PMID- 10085223
TI  - Functional production and reconstitution of the human equilibrative nucleoside
      transporter (hENT1) in Saccharomyces cerevisiae. Interaction of inhibitors of
      nucleoside transport with recombinant hENT1 and a glycosylation-defective
      derivative (hENT1/N48Q).
AB  - We have produced recombinant human equilibrative nucleoside transporter (hENT1)
      in the yeast Saccharomyces cerevisiae and have compared the binding of inhibitors
      of equilibrative nucleoside transport with the wild-type transporter and a N
      glycosylation-defective mutant transporter. Equilibrium binding of 3H-labelled
      nitrobenzylmercaptopurine ribonucleoside {6-[(4-nitrobenzyl)thio]-9-beta-d
      ribofuranosyl purine; NBMPR} to hENT1-producing yeast revealed a single class of
      high-affinity sites that were shown to be in membrane fractions by (1)
      equilibrium binding (means+/-S.D.) of [3H]NBMPR to intact yeast (Kd 1.2+/-0.2 nM;
      Bmax 5.0+/-0.5 pmol/mg of protein) and membranes (Kd 0.7+/-0.2 nM; Bmax 6.5+/-1
      pmol/mg of protein), and (2) reconstitution of hENT1-mediated [3H]thymidine
      transport into proteoliposomes that was potently inhibited by NBMPR. Dilazep and
      dipyridamole inhibited NBMPR binding to hENT1 with IC50 values of 130+/-10 and
      380+/-20 nM respectively. The role of N-linked glycosylation in the interaction
      of NBMPR with hENT1 was examined by the quantification of binding of [3H]NBMPR to
      yeast producing either wild-type hENT1 or a glycosylation-defective mutant
      (hENT1/N48Q) in which Asn-48 was converted into Gln. The Kd for binding of NBMPR
      to hENT1/N48Q was 10. 5+/-1.6 nM, indicating that the replacement of an Asn
      residue with Gln decreased the affinity of hENT1 for NBMPR. The decreased
      affinity of hENT1/N48Q for NBMPR was due to an increased rate of dissociation
      (koff) and a decreased rate of association (kon) of specifically bound [3H]NBMPR
      because the values for hENT1-producing and hENT1/N48Q-producing yeast were
      respectively 0.14+/-0.02 and 0. 36+/-0.05 min-1 for koff, and (1.2+/-0.1)x10(8)
      and (0.40+/-0. 04)x10(8) M-1.min-1 for kon. These results indicated that the
      conservative conversion of an Asn residue into Gln at position 48 of hENT1 and/or
      the loss of N-linked glycosylation capability altered the binding characteristics
      of the transporter for NBMPR, dilazep and dipyridamole.

PMID- 10085224
TI  - Position-independent and copy-number-related expression of a goat bacterial
      artificial chromosome alpha-lactalbumin gene in transgenic mice.
AB  - A bacterial artificial chromosome goat insert comprising the alpha-lactalbumin
      encoding transcription unit with approximately 150 and 10 kb of 5'- and 3'
      flanking sequences, respectively, was micro-injected into mouse eggs. In six out
      of seven transgenic lines, the level of mammary tissue- and stage-specific
      expression was position-independent and copy-number-dependent. The exogenous
      alpha-lactalbumin yield, about 0.8 mg/ml of milk per copy, compared favourably
      with the alpha-lactalbumin content of mouse and goat milks, about 0.8 and >1
      mg/ml, respectively. This suggests that the insert contains most if not all of
      the cis-acting elements involved in the full and specific expression of the goat
      alpha-lactalbumin gene and opens up opportunities to use this vector to target
      expression of foreign genes in the lactating mammary gland of transgenic animals.
      The transgene was silent in the seventh line for an unknown reason.

PMID- 10085225
TI  - Only one of the charged amino acids located in membrane-spanning regions is
      important for the function of the Saccharomyces cerevisiae uracil permease.
AB  - The transport of uracil into the yeast Saccharomyces cerevisiae is mediated by
      uracil permease, a specific co-transporter encoded by the FUR4 gene. Uracil
      permease is a multispan membrane protein that is delivered to the plasma membrane
      via the secretory pathway. Experimental results led to the proposal of a two
      dimensional model of the protein's topology. According to this model, the
      membrane domain of Fur4p contains three charged amino acid residues (Glu-243, Lys
      272 and Glu-539) that are conserved in the members of the FUR family of yeast
      transporters. We have previously shown that a mis-sense mutation leading to the
      replacement of Lys-272 by Glu severely impairs the function of uracil permease.
      In the present paper, the role of the three charged residues present in the
      membrane-spanning regions of Fur4p was further investigated by using site
      directed mutagenesis. The variant permeases were correctly targeted to the plasma
      membrane and their stabilities were similar to that of the wild-type permease.
      The effect of the mutations was studied by measuring the uptake constants for
      uracil on whole cells and equilibrium binding parameters on plasma membrane
      enriched fractions. We found no evidence for ionic interaction between either of
      the glutamic residues in transmembrane segments 3 and 9 and the lysine residue in
      transmembrane segment 4. Of the three charged residues, only Lys-272 was
      important for the transport activity of the transporter. Its replacement by Ala,
      Glu or even Arg strongly impaired both the binding and the translocation of
      uracil.

PMID- 10085226
TI  - Lignocellulose degradation by Phanerochaete chrysosporium: purification and
      characterization of the main alpha-galactosidase.
AB  - The main alpha-galactosidase was purified to homogeneity, in 30% yield, from a
      solid culture of Phanerochaete chrysosporium on 1 part wheat bran/2 parts
      thermomechanical softwood pulp. It is a glycosylated tetramer of 50 kDa peptide
      chains, which gives the N-terminal sequence
      ADNGLAITPQMG(?W)NT(?W)NHFG(?W)DIS(?W)DTI. It is remarkably stable, with crude
      extracts losing no activity over 3 h at 80 degrees C, and the purified enzyme
      retaining its activity over several months at 4 degrees C. The kinetics of
      hydrolysis at 25 degrees C of various substrates by this retaining enzyme were
      measured, absolute parameters being obtained by active-site titration with
      2',4',6'-trinitrophenyl 2-deoxy-2, 2-difluoro-alpha-D-galactopyranoside. The
      variation of kcat/Km for 1-naphthyl-alpha-D-galactopyranoside with pH is bell
      shaped, with pK1=1.91 and pK2=5.54. The alphaD(V/K) value for p-nitrophenyl-alpha
      D-glucopyranoside is 1.031+/-0.007 at the optimal pH of 3.75 and 1.114+/-0.006 at
      pH7.00, indicating masking of the intrinsic effect at optimal pH. There is no
      alpha-2H effect on binding galactose [alphaD(Ki)=0.994+/-0.013]. The enzyme
      hydrolyses p-nitrophenyl beta-L-arabinopyranoside approximately 510 times slower
      than the galactoside, but has no detectable activity on the alpha-D
      glucopyranoside or alpha-D-mannopyranoside. Hydrolysis of alpha-galactosides with
      poor leaving groups is Michaelian, but that of substrates with good leaving
      groups exhibits pronounced apparent substrate inhibition, with Kis values similar
      to Km values. We attribute this to the binding of the second substrate molecule
      to a beta-galactopyranosyl-enzyme intermediate, forming an E.betaGal. alphaGalX
      complex which turns over slowly, if at all. 1-Fluoro-alpha-D-galactopyranosyl
      fluoride, unlike alpha-D-galactopyranosyl fluoride, is a Michaelian substrate,
      indicating that the effect of 1-fluorine substitution is greater on the first
      than on the second step of the enzyme reaction.

PMID- 10085227
TI  - Conserved polar residues in the transmembrane domain of the human tachykinin NK2
      receptor: functional roles and structural implications.
AB  - We have studied the effects of agonist and antagonist binding, agonist-induced
      activation and agonist-induced desensitization of the human tachykinin NK2
      receptor mutated at polar residues Asn-51 [in transmembrane helix 1 (TM1)], Asp
      79 (TM2) and Asn-303 (TM7), which are highly conserved in the transmembrane
      domain in the rhodopsin family of G-protein-coupled receptors. Wild-type and
      mutant receptors were expressed in both COS-1 cells and Xenopus oocytes. The
      results show that the N51D mutation results in a receptor which, in contrast with
      the wild-type receptor, is desensitized by the application of a concentration of
      1 microM of the partial agonist GR64349, indicating that the mutant is more
      sensitive to agonist activation than is the wild-type receptor. In addition, we
      show that, whereas the D79E mutant displayed activation properties similar to
      those of the wild-type receptor, the D79N and D79A mutants displayed a severely
      impaired ability to activate the calcium-dependent chloride current. This
      suggests that it is the negative charge at Asn-79, rather than the ability of
      this residue to hydrogen-bond, that is critical for the activity of the receptor.
      Interestingly, the placement of a negative charge at position 303 could
      compensate for the removal of the negative charge at position 79, since the
      double mutant D79N/N303D displayed activation properties similar to those of the
      wild-type receptor. This suggests that these two residues are functionally
      coupled, and may even be in close proximity in the three-dimensional structure of
      the human tachykinin NK2 receptor. A three-dimensional model of the receptor
      displaying this putative interaction is presented.

PMID- 10085228
TI  - Mapping the active site of the Haemophilus influenzae methionyl-tRNA
      formyltransferase: residues important for catalysis and tRNA binding.
AB  - Formylation of the initiator methionyl-tRNA by methionyl-tRNA formyltransferase
      (MTF) is an essential step in initiation of protein synthesis in eubacteria.
      Here, site-directed mutagenesis was used to identify active site residues of the
      Haemophilus influenzae MTF. Of the nine residues investigated, only Arg-41, Asn
      107, His-109 and Asp-145 were important for the function of the H. influenzae
      MTF. Replacement of these residues with Ala resulted in a significant reduction
      in the efficiency of catalysis. Intrinsic fluorescence analysis indicated that
      this was not due to a defect in N10-formyltetrahydrofolate (fTHF) binding. The
      Asp-145 and Arg-41 mutations reduced the affinity of the enzyme for the initiator
      tRNA, whereas the Asn-107 and His-109 mutations affected catalysis but not tRNA
      binding. Replacement of Arg-41, His-109 and Asp-145 with functionally similar
      residues also affected the activity of the enzyme. The data suggest that Asn-107,
      His-109 and Asp-145 are catalytic residues, whereas Arg-41 is involved in tRNA
      recognition. In the Escherichia coli glycinamide ribonucleotide
      formyltransferase, which also uses fTHF as the formyl donor, Asn-106, His-108 and
      Asp-144 participate in the catalytic step. Together, these observations imply
      that this group of enzymes uses the same basic mechanism in formylating their
      substrates.

PMID- 10085229
TI  - 17beta-oestradiol increases intracellular Ca2+ concentration in rat enterocytes.
      Potential role of phospholipase C-dependent store-operated Ca2+ influx.
AB  - The involvement of the phospholipase C (PLC) pathway in the non-genomic
      regulation of duodenal cell Ca2+ concentration by 17beta-oestradiol was
      investigated. The PLC inhibitors neomycin (0.5 mM) and U-73122 (2 microM)
      suppressed the stimulatory effect of 0.1 nM 17beta-oestradiol on the 45Ca2+
      influx into enterocytes isolated from rat duodenum. The hormone (1 pM to 10 nM)
      increased the formation of 1,2-diacylglycerol in a biphasic pattern,
      characterized by an early peak at 45 s (+82%) and a later peak at 5 min (+46%).
      Both PLC inhibitors suppressed the first peak but were unable to block the 17beta
      oestradiol effect at 5 min. 17beta-Oestradiol also increased the generation of
      inositol 1,4,5-trisphosphate within 15 s, with maximal stimulation at 30 s.
      17beta-Oestradiol induced a rapid (30 s) and sustained (up to 5 min) increase in
      the intracellular Ca2+ concentration ([Ca2+]i) of fura 2-loaded enterocytes. The
      fast rise in [Ca2+]i was specific because other sex steroid hormones were without
      effect and could be blocked to a great extent by U-73122 (by 86% at 1 min). The
      effects of 17beta-oestradiol on enterocyte [Ca2+]i were decreased significantly
      (by 75%) in a Ca2+-free extracellular medium but a pronounced increase in [Ca2+]i
      was obtained after readmission of Ca2+ to the medium. The latter change was
      suppressed by 10 microM La3+, whereas nitrendipine (1 microM) and verapamil (10
      microM) separately were without effect. The permeability of the 17beta-oestradiol
      induced Ca2+ influx pathway to Mn2+ was increased 2.8-fold by treatment with
      oestrogen. These results suggest the operation of a PLC-dependent store-operated
      Ca2+ channel mechanism in 17beta-oestradiol regulation of enterocyte
      extracellular Ca2+ influx.

PMID- 10085230
TI  - Electron transfer reactions in the alkene mono-oxygenase complex from Nocardia
      corallina B-276.
AB  - Nocardia corallina B-276 possesses a multi-component enzyme, alkene mono
      oxygenase (AMO), that catalyses the stereoselective epoxygenation of alkenes. The
      reductase component of this system has been shown by EPR and fluorescence
      spectroscopy to contain two prosthetic groups, an FAD centre and a [2Fe-2S]
      cluster. The role of these centres in the epoxygenation reaction was determined
      by midpoint potential measurements and electron transfer kinetics. The order of
      potentials of the prosthetic groups of the reductase were FAD/FAD.=-216 mV, [2Fe
      2S]/[2Fe-2S].=-160 mV and FAD./FAD.=-134 mV. Combined, these data implied that
      the reductase component supplied the energy required for the epoxygenation
      reaction and allowed a prediction of the mechanism of electron transfer within
      the AMO complex. The FAD moiety was reduced by bound NADH in a two-electron
      reaction. The electrons were then transported to the [2Fe-2S] centre one at a
      time, which in turn reduced the di-iron centre of the epoxygenase. Reduction of
      the di-iron centre is required for oxygen binding and substrate oxidation.

PMID- 10085231
TI  - Characterization of the regulation of phospholipase D activity in the detergent
      insoluble fraction of HL60 cells by protein kinase C and small G-proteins.
AB  - Phospholipase D (PLD) activity has been shown to be GTP-dependent both in vivo
      and in vitro. One protein that confers GTP sensitivity to PLD activity in vitro
      is the low-molecular-mass G-protein ADP-ribosylation factor (Arf). However,
      members of the Rho family and protein kinase C (PKC) have also been reported to
      activate PLD in various cell systems. We have characterized the stimulation of
      PLD in HL60 cell membranes by these proteins. The results demonstrate that a
      considerable proportion of HL60 PLD activity is located in a detergent-insoluble
      fraction of the cell membrane that is unlikely to be a caveolae-like domain, but
      is probably cytoskeletal. This PLD activity required the presence of Arf1, a Rho
      family member and PKC for efficient catalysis of the lipid substrate, suggesting
      that the activity represents PLD1. We show that recombinant human PLD1b is
      regulated in a similar manner to HL60-membrane PLD, and that PKCalpha and
      PKCdelta are equally effective PLD activators. Therefore maximum PLD activity
      requires Arf, a Rho-family member and PKC, emphasizing the high degree of
      regulation of this enzyme.

PMID- 10085232
TI  - Determinants of specificity for aflatoxin B1-8,9-epoxide in alpha-class
      glutathione S-transferases.
AB  - We have used homology modelling, based on the crystal structure of the human
      glutathione S-transferase (GST) A1-1, to obtain the three-dimensional structures
      of rat GSTA3 and rat GSTA5 subunits bound to S-aflatoxinyl-glutathione. The
      resulting models highlight two residues, at positions 208 and 108, that could be
      important for determining, either directly or indirectly, substrate specificity
      for aflatoxin-exo-8,9-epoxide among the Alpha-class GSTs. Residues at these
      positions were mutated in human GSTA1-1 (Met-208, Leu-108), rat GSTA3-3 (Glu-208,
      His-108) and rat GSTA5-5 (Asp-208, Tyr-108): in the active rat GSTA5-5 to those
      in the inactive GSTA1-1; and in the inactive human GSTA1-1 and rat GSTA3-3 to
      those in the active rat GSTA5-5. These studies show clearly that, in all three
      GSTs, an aspartate residue at position 208 is a prerequisite for high activity in
      aflatoxin-exo-8,9-epoxide conjugation, although this alone is not sufficient;
      other residues in the vicinity, particularly residues 103-112, are important,
      perhaps for the optimal orientation of the aflatoxin-exo-8,9-epoxide in the
      active site for catalysis to occur.

PMID- 10085233
TI  - Nematode pyruvate dehydrogenase kinases: role of the C-terminus in binding to the
      dihydrolipoyl transacetylase core of the pyruvate dehydrogenase complex.
AB  - Pyruvate dehydrogenase kinases (PDKs) from the anaerobic parasitic nematode
      Ascaris suum and the free-living nematode Caenorhabditis elegans were
      functionally expressed with hexahistidine tags at their N-termini and purified to
      apparent homogeneity. Both recombinant PDKs (rPDKs) were dimers, were not
      autophosphorylated and exhibited similar specific activities with the A. suum
      pyruvate dehydrogenase (E1) as substrate. In addition, the activities of both
      PDKs were activated by incubation with PDK-depleted A. suum muscle pyruvate
      dehydrogenase complex (PDC) and were stimulated by NADH and acetyl-CoA. However,
      the recombinant A. suum PDK (rAPDK) required higher NADH/NAD+ ratios for half
      maximal stimulation than the recombinant C. elegans PDK (rCPDK) or values
      reported for mammalian PDKs, as might be predicted by the more reduced
      microaerobic mitochondrial environment of the APDK. Limited tryptic digestion of
      both rPDKs yielded stable fragments truncated at the C-termini (trPDKs). The
      trPDKs retained their dimeric structure and exhibited substantial PDK activity
      with the A. suum E1 as substrate, but PDK activity was not activated by
      incubation with PDK-depleted A. suum PDC or stimulated by elevated NADH/NAD+ or
      acetyl-CoA/CoA ratios. Direct-binding assays demonstrated that increasing amounts
      of rCPDK bound to the A. suum PDK-depleted PDC. No additional rCPDK binding was
      observed at ratios greater than 20 mol of rCPDK/mol of PDC. In contrast, the
      truncated rCPDK (trCPDK) did not exhibit significant binding to the PDC.
      Similarly, a truncated form of rCPDK, rCPDK1-334, generated by mutagenesis,
      exhibited properties similar to those observed for trCPDK. These results suggest
      that the C-terminus of the PDK is not required for subunit association of the
      homodimer or catalysis, but instead seems to be involved in the binding of the
      PDKs to the dihydrolipoyl transacetylase core of the complex.

PMID- 10085234
TI  - cDNA cloning and expression of rat homeobox gene, Hex, and functional
      characterization of the protein.
AB  - We isolated two cDNA clones of rat Hex, a homeobox protein, studied its
      expression in rat liver and various cells, and characterized the protein. The
      levels of Hex mRNA were only slightly increased in liver of rats refed with a
      high-carbohydrate diet or after partial hepatectomy. Whereas the expression of
      Hex mRNA was detected in hepatocytes isolated from adult rat liver and also in
      highly differentiated hepatoma cells, no Hex mRNA was detected in poorly
      differentiated hepatoma cells. Hex mRNA was also detected in liver from embryo
      aged 15 days. Expression of Hex was increased in F9 cells during differentiation
      into visceral endoderm cells by treatment with retinoic acid. This stimulation
      occurred prior to an increase in the level of alpha-fetoprotein mRNA. When fusion
      protein expression vectors of GAL4 DNA-binding domain and Hex were co-transfected
      with luciferase reporter plasmid, with or without five copies of the GAL4-binding
      site, into HepG2 cells, the luciferase activities were decreased in concentration
      and GAL4-binding site-dependent manners. This repression did not require the
      presence of the homeodomain, which is located between the amino acid residues 137
      and 196. Its repression domain was mapped between the residues 45 and 136 in the
      proline-rich N-terminal region. In addition, the homeodomain was responsible for
      DNA-binding of Hex. These results indicate that Hex functions as a
      transcriptional repressor and may be involved in the differentiation and/or
      maintenance of the differentiated state in hepatocytes.

PMID- 10085235
TI  - Characterization of beta2 (CD18) integrin phosphorylation in phorbol ester
      activated T lymphocytes.
AB  - Integrins are transmembrane proteins involved in cell-cell and cell-extracellular
      matrix interactions. The affinity and avidity of integrins for their ligands
      change in response to cytoplasmic signals. This 'inside-out' activation has been
      reported to occur also with beta2 integrins (CD18). The beta2 integrin subunit
      has previously been shown to become phosphorylated in T lymphocytes on
      cytoplasmic serine and the functionally important threonine residues after
      treatment with phorbol esters or on triggering of T-cell receptors. We have now
      characterized the phosphorylation of beta2 integrins in T-cells in more detail.
      When T-cells were activated by phorbol esters the phosphorylation was mainly on
      Ser756. After inhibition of serine/threonine phosphatases, phosphorylation was
      also found in two of the threonine residues in the threonine triplet 758-760 of
      the beta2 cytoplasmic domain. Activation of T-cells by phorbol esters resulted in
      phosphorylation in only approx. 10% of the integrin molecules. Okadaic acid
      increased this phosphorylation to approx. 30% of the beta2 molecules, assuming
      three phosphorylation sites. This indicates that a strong dynamic phosphorylation
      exists in serine and threonine residues of the beta2 integrins.

PMID- 10085236
TI  - ATPase activity associated with the magnesium-protoporphyrin IX chelatase enzyme
      of Synechocystis PCC6803: evidence for ATP hydrolysis during Mg2+ insertion, and
      the MgATP-dependent interaction of the ChlI and ChlD subunits.
AB  - Insertion of Mg2+ into protoporphyrin IX catalysed by the three-subunit enzyme
      magnesium-protoporphyrin IX chelatase (Mg chelatase) is thought to be a two-step
      reaction, consisting of activation followed by Mg2+ chelation. The activation
      step requires ATP and two of the subunits, ChlI and ChlD (I and D respectively),
      and it has been speculated that this step results in the formation of an I-D-ATP
      complex. The subsequent step, in which Mg2+ is inserted into protoporphyrin, also
      requires ATP and the third subunit, H, in addition to ATP-activated I-D complex.
      In the present study, we examine the interaction of the I and D subunits of the
      Mg chelatase from the cyanobacterium Synechocystis PCC 6803. We demonstrate the
      purification of an I-D complex, and show that ATP and Mg2+ are absolute
      requirements for the formation of this complex, probably as MgATP. However, ATP
      may be replaced by the slowly hydrolysable analogue, adenosine 5'-[gamma
      thio]triphosphate, and, to a minor extent, by ADP and the non-hydrolysable ATP
      analogue, adenosine 5'-[beta,gamma-imido]triphosphate, all of which suggests that
      ATP hydrolysis is not necessary for the formation of the ChlI-ChlD complex. A
      sensitive continuous assay was used to detect ATPase activity during Mg2+
      chelation, and it was found that the maximum rate of ATP hydrolysis coincided
      with the maximum rate of Mg2+ insertion. The rate of ATP hydrolysis depended on
      factors that determined the rate of Mg2+ chelation, such as increasing the
      concentration of the H subunit and the concentration of protoporphyrin. Thus ATP
      hydrolysis has been identified as an absolute requirement for the chelation step.
      The I subunit possessed strong ATPase activity when assayed on its own, whereas
      the D subunit had no detectable activity, and when the I and D subunits were
      assayed in combination, the ATPase activity of the I subunit was repressed.

PMID- 10085237
TI  - Complexes containing activating transcription factor (ATF)/cAMP-responsive
      element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein
      (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress
      response.
AB  - Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding
      protein (C/EBP) transcription factor family and is transcriptionally activated by
      cellular stress signals. We recently demonstrated that arsenite treatment of rat
      pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA
      expression, controlled in part through binding of C/EBPbeta and two
      uncharacterized protein complexes to the C/EBP-ATF (activating transcription
      factor) composite site in the Gadd153 promoter. In this report, we identified
      components of these additional complexes as two ATF/CREB (cAMP-responsive-element
      binding protein) transcription factors having differential binding activities
      dependent upon the time of arsenite exposure. During arsenite treatment of PC12
      cells, we observed enhanced binding of ATF4 to the C/EBP-ATF site at 2 h as
      Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as
      Gadd153 expression declined. We further demonstrated that ATF4 activates, while
      ATF3 represses, Gadd153 promoter activity through the C/EBP-ATF site. ATF3 also
      repressed ATF4-mediated transactivation and arsenite-induced activation of the
      Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB
      family are involved in the cellular stress response, and that regulation of
      stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered,
      sequential binding of multiple transcription factor complexes to the C/EBP-ATF
      composite site.

PMID- 10085238
TI  - Purified meningococcal transferrin-binding protein B interacts with a secondary,
      strain-specific, binding site in the N-terminal lobe of human transferrin.
AB  - Neisseria meningitidis, grown in iron-limited conditions, produces two
      transferrin-binding proteins (TbpA and TbpB) that independently and specifically
      bind human serum transferrin (hTF) but not bovine serum transferrin (bTF). We
      have used surface plasmon resonance to characterize the interaction between
      individual TbpA and TbpB and a series of full-length human-bovine chimaeric
      transferrins (hbTFs) under conditions of variable saturation with iron. A
      comparative analysis of hTF and hbTF chimaera-binding data confirmed that the
      major features involved in Tbp binding are located in the C-terminal lobe of hTF
      and that isolated TbpA can recognize distinct sites present in, or
      conformationally influenced by, residues 598-679. Binding by TbpB was maintained
      at a significant but decreased level after replacement of the entire hTF C
      terminal lobe by the equivalent bovine sequence. The extent of this binding
      difference was dependent on the meningococcal strain and on the presence of hTF
      residues 255-350. This indicated that TbpB from strain SD has a secondary, strain
      specific, binding site located within this region, whereas TbpB from strain B16B6
      does not share this recognition site. Binding of TbpA was influenced primarily by
      sequence substitutions in the hTF C-terminal lobe, and co-purified TbpA and TbpB
      (TbpA+B) was functionally distinct from either of its components. The limited
      divergence between hTF and bTF has been related to observed differences in
      binding by Tbps and has been used to delineate those regions of hTF that are
      important for such interactions.

PMID- 10085239
TI  - Transcriptional regulation of the human asparagine synthetase gene by
      carbohydrate availability.
AB  - Transcription of the asparagine synthetase (AS) gene is induced by amino acid
      deprivation. The present data illustrate that this gene is also under
      transcriptional control by carbohydrate availability. Incubation of human HepG2
      hepatoma cells in glucose-free medium resulted in an increased AS mRNA content,
      reaching a maximum of about 14-fold over control cells after approx. 12 h.
      Extracellular glucose caused the repression of the content of AS mRNA in a
      concentration-dependent manner, with a k1/2 (concentration causing a half-maximal
      repression) of 1 mM. Fructose, galactose, mannose, 2-deoxyglucose and xylitol
      were found to maintain the mRNA content of both AS and the glucose-regulated
      protein GRP78 in a state of repression, whereas 3-O-methylglucose did not.
      Incubation in either histidine-free or glucose-free medium also resulted in
      adaptive regulation of the AS gene in BNL-CL.2 mouse hepatocytes, rat C6 glioma
      cells and human MOLT4 lymphocytes, in addition to HepG2 cells. In contrast, the
      steady-state mRNA content of GRP78 was unaffected by amino acid availability.
      Transient transfection assays using a reporter gene construct documented that
      glucose deprivation increases AS gene transcription via elements within the
      proximal 3 kbp of the AS promoter. These results illustrate that human AS gene
      transcription is induced following glucose limitation of the cells.

PMID- 10085240
TI  - SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can
      function in insulin secretion.
AB  - The tSNARE (the target-membrane soluble NSF-attachment protein receptor, where
      NSF is N-ethylmaleimide-sensitive fusion protein) synaptosomal-associated protein
      of 25 kDa (SNAP-25) is expressed in pancreatic B-cells and its cleavage by
      botulinum neurotoxin E (BoNT/E) abolishes stimulated secretion of insulin. In the
      nervous system, two SNAP-25 isoforms (a and b) have been described that are
      produced by alternative splicing. Here it is shown, using reverse transcriptase
      PCR, that messages for both SNAP-25 isoforms are expressed in primary pancreatic
      B and non-B cells as well as in insulin-secreting cell lines. After transfection,
      both isoforms can be detected at the plasma membrane as well as in an
      intracellular perinuclear region in the insulin-secreting cell line, HIT. To test
      for the functional role of the two isoforms in insulin secretion, mutant forms of
      SNAP-25a and b resistant against cleavage by BoNT/E were generated. Such mutant
      SNAP-25, when expressed in HIT cells, is not inactivated by BoNT/E and its
      ability to restore insulin secretion can thus be investigated. To obtain the
      toxin-resistant mutant isoforms, the sequence around the BoNT/E cleavage site
      (R176QIDRIM182) was changed to P176QIKRIT182. This is the sequence of the
      equivalent region of human SNAP-23 (P187-T194), which has been shown to be
      resistant to BoNT/E. The mutant SNAP-25 was resistant to BoNT/E in vitro and in
      vivo and both mutant isoforms were able to reconstitute insulin secretion from
      toxin-treated HIT cells.

PMID- 10085241
TI  - Selective loss of PMA-stimulated expression of matrix metalloproteinase 1 in
      HaCaT keratinocytes is correlated with the inability to induce mitogen-activated
      protein family kinases.
AB  - Many cell types, including fibroblasts and primary keratinocytes, increase matrix
      metalloproteinase 1 (MMP-1) production in response to agonists such as growth
      factors and phorbol esters. However, the spontaneously transformed human
      keratinocyte cell line HaCaT, although it increases MMP-1 production in response
      to epidermal growth factor (EGF), does not respond similarly to stimulation with
      PMA. This phenomenon occurs even though HaCaT cells remain proliferatively
      responsive to both agonists, suggesting a HaCaT-specific defect in a PMA-mediated
      signal transduction pathway. Using an inside-out approach to elucidate the source
      of this defect, we found that EGF, but not PMA, stimulated MMP-1 promoter
      activity in transiently transfected HaCaT keratinocytes. In addition, an
      assessment of fibroblast and HaCaT c-fos and c-jun gene expression after exposure
      to EGF and PMA showed that although both agonists increased the expression of c
      fos and c-jun mRNA in fibroblasts, only EGF did so in HaCaT keratinocytes.
      Finally, we looked at the activation of mitogen-activated protein (MAP) family
      kinases after stimulation with EGF or PMA and found that both agonists increased
      the phosphorylation and activation of fibroblast extracellular signal-regulated
      protein kinase and c-Jun N-terminal kinase, but only EGF activated the same
      kinase activities in HaCaT cells. Further, the EGF-mediated increase in MMP-1
      gene expression was inhibited by the MAP kinase/ERK kinase (MEK)-specific
      inhibitor PD98059 and the p38 kinase-specific inhibitor SB203580. Our evidence
      indicates that although HaCaT MAP kinases are functional, they are not properly
      regulated in response to the activation of protein kinase C, and that the defect
      that bars HaCaT MMP-1 expression in response to stimulation with PMA lies before
      MAP kinase activation.

PMID- 10085242
TI  - Structure and chromosomal assignment of the human lectin-like oxidized low
      density-lipoprotein receptor-1 (LOX-1) gene.
AB  - We have reported the cDNA cloning of a modified low-density-lipoprotein (LDL)
      receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is
      postulated to be involved in endothelial dysfunction and the pathogenesis of
      atherosclerosis. Here, we determined the organization of the human LOX-1 gene,
      including the 5'-regulatory region. The 5'-regulatory region contained several
      potential cis-regulatory elements, such as GATA-2 binding element, c-ets-1
      binding element, 12-O-tetradecanoylphorbol 13-acetate-responsive element and
      shear-stress-responsive elements, which may mediate the endothelium-specific and
      inducible expression of LOX-1. The major transcription-initiation site was found
      to be located 29 nucleotides downstream of the TATA box and 61 nucleotides
      upstream from the translation-initiation codon. The minor initiation site was
      found to be 5 bp downstream from the major site. Most of the promoter activity of
      the LOX-1 gene was ascribed to the region (-150 to -90) containing the GC and
      CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first
      3 exons corresponded to the different functional domains of the protein
      (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded
      the carbohydrate-recognition domain similar to the case of other C-type lectin
      genes. The LOX-1 gene was a single-copy gene and assigned to the p12.3-p13.2
      region of chromosome 12. Since the locus for a familial hypertension has been
      mapped to the overlapping region, LOX-1 might be the gene responsible for the
      hypertension.

PMID- 10085243
TI  - Mammalian PIG-L and its yeast homologue Gpi12p are N
      acetylglucosaminylphosphatidylinositol de-N-acetylases essential in
      glycosylphosphatidylinositol biosynthesis.
AB  - Glycosylphosphatidylinositol (GPI) is used as a membrane anchor by many
      eukaryotic cell-surface proteins. The second step of GPI biosynthesis is de-N
      acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). We have
      previously cloned the rat PIG-L gene by expression cloning that complemented a
      mutant Chinese hamster ovary cell line defective in this step. Here we show that
      recombinant rat PIG-L protein purified from Escherichia coli as a complex with
      GroEL has GlcNAc-PI de-N-acetylase activity in vitro. The activity was not
      enhanced by GTP, which is known to enhance the de-N-acetylase activity of
      mammalian cell microsomes. As with other de-N-acetylases that act on the GlcNAc
      moiety, metal ions, in particular Mn2+ and Ni2+, enhanced the enzyme activity of
      PIG-L. The Saccharomyces cerevisiae YMR281W open reading frame encodes a protein
      (termed Gpi12p) with 24% amino acid identity with rat PIG-L. On transfection into
      mammalian PIG-L-deficient cells, this gene, GPI12, restored the cell-surface
      expression of GPI-anchored proteins and GlcNAc-PI de-N-acetylase activity. The
      disruption of the gene caused lethality in S. cerevisiae. These results indicate
      that GlcNAc-PI de-N-acetylase is conserved between mammals and yeasts and that
      the de-N-acetylation step is also indispensable in yeasts.

PMID- 10085244
TI  - High-affinity binding of very-long-chain fatty acyl-CoA esters to the peroxisomal
      non-specific lipid-transfer protein (sterol carrier protein-2).
AB  - Binding of fluorescent fatty acids to bovine liver non-specific lipid-transfer
      protein (nsL-TP) was assessed by measuring fluorescence resonance energy transfer
      (FRET) between the single tryptophan residue of nsL-TP and the fluorophore. Upon
      addition of pyrene dodecanoic acid (Pyr-C12) and cis-parinaric acid to nsL-TP,
      FRET was observed indicating that these fatty acids were accommodated in the
      lipid binding site closely positioned to the tryptophan residue. Substantial
      binding was observed only when these fatty acids were presented in the monomeric
      form complexed to beta-cyclodextrin. As shown by time-resolved fluorescence
      measurements, translocation of Pyr-C12 from the Pyr-C12-beta-cyclodextrin complex
      to nsL-TP changed dramatically the direct molecular environment of the pyrene
      moiety: i.e. the fluorescence lifetime of the directly excited pyrene increased
      at least by 25% and a distinct rotational correlation time of 7 ns was observed.
      In order to evaluate the affinity of nsL-TP for intermediates of the beta
      oxidation pathway, a binding assay was developed based on the ability of fatty
      acyl derivatives to displace Pyr-C12 from the lipid binding site as reflected by
      the reduction of FRET. Hexadecanoyl-CoA and 2-hexadecenoyl-CoA were found to bind
      readily to nsL-TP, whereas 3-hydroxyhexadecanoyl-CoA and 3-ketohexadecanoyl-CoA
      bound poorly. The highest affinities were observed for the very-long-chain fatty
      acyl-CoA esters (24:0-CoA, 26:0-CoA) and their enoyl derivatives (24:1-CoA, 26:1
      CoA). Binding of non-esterified hexadecanoic acid and tetracosanoic acid (24:0)
      was negligible.

PMID- 10085245
TI  - Kinetic properties and tissular distribution of mammalian phosphomannomutase
      isozymes.
AB  - Human tissues contain two types of phosphomannomutase, PMM1 and PMM2. Mutations
      in the PMM2 gene are responsible for the most common form of carbohydrate
      deficient glycoprotein syndrome [Matthijs, Schollen, Pardon, Veiga-da-Cunha,
      Jaeken, Cassiman and Van Schaftingen (1997) Nat. Genet. 19, 88-92]. The protein
      encoded by this gene has now been produced in Escherichia coli and purified to
      homogeneity, and its properties have been compared with those of recombinant
      human PMM1. PMM2 converts mannose 1-phosphate into mannose 6-phosphate about 20
      times more rapidly than glucose 1-phosphate to glucose 6-phosphate, whereas PMM1
      displays identical Vmax values with both substrates. The Ka values for both
      mannose 1,6-bisphosphate and glucose 1,6-bisphosphate are significantly lower in
      the case of PMM2 than in the case of PMM1. Like PMM1, PMM2 forms a phosphoenzyme
      with the chemical characteristics of an acyl-phosphate. PMM1 and PMM2 hydrolyse
      different hexose bisphosphates (glucose 1,6-bisphosphate, mannose 1,6
      bisphosphate, fructose 1,6-bisphosphate) at maximal rates of approximately 3.5
      and 0.3% of their PMM activity, respectively. Fructose 1,6-bisphosphate does not
      activate PMM2 but causes a time-dependent stimulation of PMM1 due to the
      progressive formation of mannose 1,6-bisphosphate from fructose 1,6-bisphosphate
      and mannose 1-phosphate. Experiments with specific antibodies, kinetic studies
      and Northern blots indicated that PMM2 is the only detectable isozyme in most rat
      tissues except brain and lung, where PMM1 accounts for about 66 and 13% of the
      total activities, respectively.

PMID- 10085246
TI  - Organization and alternative splicing of the Caenorhabditis elegans cAMP
      dependent protein kinase catalytic-subunit gene (kin-1).
AB  - The cAMP-dependent protein kinase (protein kinase A, PK-A) is multifunctional in
      nature, with key roles in the control of diverse aspects of eukaryotic cellular
      activity. In the case of the free-living nematode, Caenorhabditis elegans, a gene
      encoding the PK-A catalytic subunit has been identified and two isoforms of this
      subunit, arising from a C-terminal alternative-splicing event, have been
      characterized [Gross, Bagchi, Lu and Rubin (1990) J. Biol. Chem. 265, 6896-6907].
      Here we report the occurrence of N-terminal alternative-splicing events that, in
      addition to generating a multiplicity of non-myristoylatable isoforms, also
      generate the myristoylated variant(s) of the catalytic subunit that we have
      recently characterized [Aspbury, Fisher, Rees and Clegg (1997) Biochem. Biophys.
      Res. Commun. 238, 523-527]. The gene spans more than 36 kb and is divided into a
      total of 13 exons. Each of the mature transcripts contains only 7 exons. In
      addition to the already characterized exon 1, the 5'-untranslated region and
      first intron actually contain 5 other exons, any one of which may be
      alternatively spliced on to exon 2 at the 5' end of the pre-mRNA. This N-terminal
      alternative splicing occurs in combination with either of the already
      characterized C-terminal alternative exons. Thus, C. elegans expresses at least
      12 different isoforms of the catalytic subunit of PK-A. The significance of this
      unprecedented structural diversity in the family of PK-A catalytic subunits is
      discussed.

PMID- 10085247
TI  - Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle:
      evidence that thin filaments rearrange to form striated myofibrils.
AB  - Actin filament lengths in muscle and nonmuscle cells are believed to depend on
      the regulated activity of capping proteins at both the fast growing (barbed) and
      slow growing (pointed) filament ends. In striated muscle, the pointed end capping
      protein, tropomodulin, has been shown to maintain the lengths of thin filaments
      in mature myofibrils. To determine whether tropomodulin might also be involved in
      thin filament assembly, we investigated the assembly of tropomodulin into
      myofibrils during differentiation of primary cultures of chick skeletal muscle
      cells. Our results show that tropomodulin is expressed early in differentiation
      and is associated with the earliest premyofibrils which contain overlapping and
      misaligned actin filaments. In addition, tropomodulin can be found in actin
      filament bundles at the distal tips of growing myotubes, where sarcomeric alpha
      actinin is not always detected, suggesting that tropomodulin caps actin filament
      pointed ends even before the filaments are cross-linked into Z bodies by alpha
      actinin. Tropomodulin staining exhibits an irregular punctate pattern along the
      length of premyofibrils that demonstrate a smooth phalloidin staining pattern for
      F-actin. Strikingly, the tropomodulin dots often appear to be located between the
      closely spaced, dot-like Z bodies that are stained for (&agr;)-actinin. Thus, in
      the earliest premyofibrils, the pointed ends of the thin filaments are clustered
      and partially aligned with respect to the Z bodies (the location of the barbed
      filament ends). At later stages of differentiation, the tropomodulin dots become
      aligned into regular periodic striations concurrently with the appearance of
      striated phalloidin staining for F-actin and alignment of Z bodies into Z lines.
      Tropomodulin, together with the barbed end capping protein, CapZ, may function
      from the earliest stages of myofibrillogenesis to restrict the lengths of newly
      assembled thin filaments by capping their ends; thus, transitions from
      nonstriated to striated myofibrils in skeletal muscle are likely due principally
      to filament rearrangements rather than to filament polymerization or
      depolymerization. Rearrangements of actin filaments capped at their pointed and
      barbed ends may be a general mechanism by which cells restructure their actin
      cytoskeletal networks during cell growth and differentiation.

PMID- 10085248
TI  - An arrested late endosome-lysosome intermediate aggregate observed in a Chinese
      hamster ovary cell mutant isolated by novel three-step screening.
AB  - Chinese hamster ovary cell mutants defective in the post-uptake degradation of
      low-density lipoprotein (LDL) in lysosomes were selected from mutagenized cells
      by novel three-step screening. First, in the presence of LDL, clones sensitive to
      an inhibitor of the rate-limiting enzyme of the cholesterol biosynthetic pathway,
      3-hydroxy-3-methylglutaryl-CoA reductase, were isolated. Second, from the
      selected clones, those lacking in the degradation of a constituent of a
      fluorescent LDL were qualitatively screened by microscopy. Third, the clones were
      further screened by previously established quantitative analytical flow cytometry
      that detects the early-phase disintegration of LDL by lysosomal acid hydrolases.
      One of the isolated mutant clones, LEX1 (Lysosome-Endosome X 1), was a recessive
      mutant, and exhibited a specific disorder in the late endocytic pathway. LEX1
      cells showed an unusual perinuclear aggregate of vesicles, heterogeneously
      positive for lysosomal glycoprotein-B/cathepsin D and rab7, yet negative for the
      cation-independent mannose 6-phosphate receptor. The aggregate was formed around
      the microtubule organizing center, and was disrupted by nocodazole treatment.
      Internalized octadecyl rhodamine B-labeled LDL (R18-LDL) was accumulated in the
      perinuclear rab7-positive vesicles. In a Percoll density gradient, neither
      internalized R18-LDL nor internalized horseradish peroxidase was efficiently
      chased into heavy lysosomal fractions positive for beta-hexosaminidase. LEX1
      cells showed differences in the activity and subcellular distribution of
      lysosomal enzymes. These characteristics of LEX1 cells are consistent with the
      ideas that the perinuclear vesicle aggregate is an arrested intermediate of
      direct fusion or divergence between lysosomes and rab7-positive, cation
      independent mannose 6-phosphate receptor-negative late endosomes, and that
      equilibrium between the lysosomes and the late endosomes is shifted towards the
      late endosomes in LEX1 cells. Such fusion or divergence between the late
      endosomes and the lysosomes would determine an appropriate equilibrium between
      them, and might thereby play an important role for proper lysosomal digestive
      functions. LEX1 mutant cells would be helpful for the dissection of the as yet
      unrevealed details of the late endocytic membrane dynamics and for the
      identification of factors involved in the process arrested by the mutation.

PMID- 10085249
TI  - Nucleo-cytoplasmic interactions that control nuclear envelope breakdown and entry
      into mitosis in the sea urchin zygote.
AB  - In sea urchin zygotes and mammalian cells nuclear envelope breakdown (NEB) is not
      driven simply by a rise in cytoplasmic cyclin dependent kinase 1-cyclin B (Cdk1
      B) activity; the checkpoint monitoring DNA synthesis can prevent NEB in the face
      of mitotic levels of Cdk1-B. Using sea urchin zygotes we investigated whether
      this checkpoint prevents NEB by restricting import of regulatory proteins into
      the nucleus. We find that cyclin B1-GFP accumulates in nuclei that cannot
      complete DNA synthesis and do not break down. Thus, this checkpoint limits NEB
      downstream of both the cytoplasmic activation and nuclear accumulation of Cdk1
      B1. In separate experiments we fertilize sea urchin eggs with sperm whose DNA has
      been covalently cross-linked to inhibit replication. When the pronuclei fuse, the
      resulting zygote nucleus does not break down for >180 minutes (equivalent to
      three cell cycles), even though Cdk1-B activity rises to greater than mitotic
      levels. If pronuclear fusion is prevented, then the female pronucleus breaks down
      at the normal time (average 68 minutes) and the male pronucleus with cross-linked
      DNA breaks down 16 minutes later. This male pronucleus has a functional
      checkpoint because it does not break down for >120 minutes if the female
      pronucleus is removed just prior to NEB. These results reveal the existence of an
      activity released by the female pronucleus upon its breakdown, that overrides the
      checkpoint in the male pronucleus and induces NEB. Microinjecting wheat germ
      agglutinin into binucleate zygotes reveals that this activity involves molecules
      that must be actively translocated into the male pronucleus.

PMID- 10085250
TI  - Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their
      carboxyl-terminal threonine phosphorylated in cultured cells and tissues.
AB  - Ezrin/radixin/moesin (ERM) proteins are thought to play an important role in
      organizing cortical actin-based cytoskeletons through cross-linkage of actin
      filaments with integral membrane proteins. Recent in vitro biochemical studies
      have revealed that ERM proteins phosphorylated on their COOH-terminal threonine
      residue (CPERMs) are active in their cross-linking activity, but this has not yet
      been evaluated in vivo. To immunofluorescently visualize CPERMs in cultured cells
      as well as tissues using a mAb specific for CPERMs, we developed a new fixation
      protocol using trichloroacetic acid (TCA) as a fixative. Immunoblotting analyses
      in combination with immunofluorescence microscopy showed that TCA effectively
      inactivated soluble phosphatases, which maintained the phosphorylation level of
      CPERMs during sample processing for immunofluorescence staining.
      Immunofluorescence microscopy with TCA-fixed samples revealed that CPERMs were
      exclusively associated with plasma membranes in a variety of cells and tissues,
      whereas total ERM proteins were distributed in both the cytoplasm and plasma
      membranes. Furthermore, the amounts of CPERMs were shown to be regulated in a
      cell and tissue type-dependent manner. These findings favored the notion that
      phosphorylation of the COOH-terminal threonine plays a key role in the regulation
      of the cross-linking activity of ERM proteins in vivo.

PMID- 10085251
TI  - Cloning, sequencing, and nucleolar targeting of the basal-body-binding nucleolar
      protein BN46/51.
AB  - BN46/51 is an acidic protein found in the granular component of the nucleolus of
      the amebo-flagellate Naegleria gruberi. When Naegleria amebae differentiate into
      swimming flagellates, BN46/51 is found associated with the basal body complex at
      the base of the flagella. In order to determine the factors responsible for
      targeting BN46/51 to a specific subnucleolar region, cDNAs coding for both
      subunits were isolated and sequenced. Two clones, JG4.1 and JG12.1 representing
      the 46 kDa and 51 kDa subunits, respectively, were investigated in detail. JG12.1
      encoded a polypeptide of 263 amino acids with a predicted size of 30.1 kDa that
      co-migrated with the 51 kDa subunit of BN46/51 when expressed in yeast. JG4.1
      encoded a polypeptide of 249 amino acids with a predicted size of 28.8 kDa that
      co-migrated with the 46 kDa subunit of BN46/51. JG4.1 was identical to JG12.1
      except for the addition of an aspartic acid between positions 94 and 95 of the
      JG12.1 sequence and the absence of 45 amino acids beginning at position 113. The
      predicted amino acid sequences were not closely related to any previously
      reported. However, the sequences did have 26-31% identity to a group of FKPBs
      (FK506 binding proteins) but lacked the peptidyl-prolyl cis-trans isomerase
      domain of the FKBPs. Both subunits contained two KKE and three KKX repeats found
      in other nucleolar proteins and in some microtubule binding proteins. Using 'Far
      Western' blots of nucleolar proteins, BN46/51 bound to polypeptides of 44 kDa and
      74 kDa. The 44 kDa component was identified as the Naegleria homologue of
      fibrillarin. BN46/51 bound specifically to the nucleoli of fixed mammalian cells,
      cells which lack a BN46/51 related polypeptide. When the JG4.1 and JG12.1 cDNAs
      were expressed in yeast, each subunit was independently targeted to the yeast
      nucleolus. We conclude that BN46/51 represents a unique nucleolar protein that
      can form specific complexes with fibrillarin and other nucleolar proteins. We
      suggest that the association of BN46/51 with the MTOC of basal bodies may reflect
      its role in connecting the nucleolus with the MTOC activity for the mitotic
      spindle. This would provide a mechanism for nucleolar segregation during the
      closed mitosis of Naegleria amebae.

PMID- 10085252
TI  - Regulation of actin organisation by TGF-beta in H-ras-transformed fibroblasts.
AB  - The actin cytoskeleton undergoes architectural changes during the processes of
      cell transformation and tumourigenesis. Transforming growth factors beta arrest
      cell cycle progression, regulate differentiation and modulate the onset of
      oncogenesis and tumourigenesis. Here, we investigated the direct role of
      transforming growth factor beta-1 in altering the transformed phenotype and
      regulating the actin organisation of oncogenic fibroblasts that constitutively or
      inducibly express the H-ras oncogene. Following transforming growth factor beta-1
      treatment, these transformed fibroblasts undergo a dramatic morphological
      alteration that includes a discrete reorganisation of their actin cytoskeleton
      and focal adhesions. Quantitative biochemical analysis demonstrated that
      transforming growth factor beta-1 potently induced polymerisation of globular to
      filamentous actin, thus corroborating the morphological analysis. The effect of
      transforming growth factor beta-1 on the cytoskeleton correlates with the ability
      of this cytokine to suppress anchorage-independent growth of the transformed
      fibroblasts. Furthermore, transforming growth factor beta-1 upregulates
      considerably the levels of the RhoB small GTPase and less the RhoA levels.
      Finally, The beta GTPase inhibitor, C3 exotransferase, blocks the ability of TGF
      beta1 to induce cytoskeletal reorganisation. These findings indicate that
      transforming growth factor beta can regulate cell morphology and growth in a
      concerted manner possibly via mechanisms that control the actin cytoskeleton.

PMID- 10085253
TI  - Is arcA3 a possible mediator in the signal transduction pathway during agonist
      cell cycle arrest by salicylic acid and UV irradiation?
AB  - Progression of BY-2 tobacco cells through the cell cycle was followed after
      treatments with ultra violet (UV) and salicylic acid (SA) used as a potent
      inhibitor of the octadecanoid pathway which can mediate response to UV
      irradiation. Cells in S phase were more sensitive than G0/G1 or G2 cells to UV
      irradiation. Although SA efficiently blocked cells in G0/G1 or G2, it did not
      block S phase synchronized cells. UV and SA applied simultaneously to cells in
      G0/G1 delayed the cell cycle progression more than each one separately. Therefore
      UV irradiation and SA act as agonists to arrest BY-2 cells at cell cycle entry.
      To further investigate the signalling pathway mediating UV response, we
      complemented a UV-sensitive Escherichia coli strain with a Nicotiana xanthi cDNA
      expression library. A cDNA (arcA3) whose coding sequence is identical to the 2,4
      D induced arcA cDNA cloned by Ishida et al. (1993) was isolated. We show that
      arcA3 transcription is induced at cell cycle entry but not directly by the 2,4-D
      treatment. Moreover, arcA3 transcription is induced prior to the restriction
      point as shown with the CDK inhibitor roscovitine. The arcA3 transcription level
      is increased by UV irradiation but prevented by SA. Indeed, addition of SA prior
      to UV irradiation blocks the induction of arcA3 transcription. This suggests that
      arcA3 gene is modulated in both UV and SA responses, the SA effect preceding the
      UV step. Since arcA3 is 67% similar to RACK1 (functional homology), a rat
      intracellular receptor for protein kinase C, and possesses identical PKC fixation
      motifs, it is hypothesised that the arcA3 gene is involved in UV and SA cell
      cycle arrest.

PMID- 10085254
TI  - Myosin IB from Entamoeba histolytica is involved in phagocytosis of human
      erythrocytes.
AB  - Entamoeba histolytica is a protozoan parasite that causes amoebic dysentery in
      humans. The disease is prevalent worldwide. Infection with E. histolytica results
      in invasion of the intestine by the parasite, followed by tissue damage and
      inflammation. During this invasive process, parasites kill and phagocytose human
      epithelial cells, immune cells and erythrocytes. Expression of amoebic
      pathogenicity requires a dynamic cytoskeleton that allows movement, tissue
      penetration and changes in parasite morphology. Myosin IB is a member of the
      myosin I family of motor proteins. Studies conducted both with Dictyostelium
      discoideum, a non-pathogenic amoeba, and with the yeast Saccharomyces cerevisiae
      indicate the involvement of myosin IB in cellular processes including movement,
      phagocytosis and endocytosis. Recently, we isolated the gene encoding myosin IB
      from E. histolytica. Thus, we decided to analyze the role of myosin IB in
      pathogenesis of amoeba. Using a specific anti-myosin IB antibody, this protein
      was localized in cell regions including the pseudopod, vesicles and underneath
      the plasma membrane. When E. histolytica was activated for erythrophagocytosis,
      myosin IB was markedly recruited to both the phagocytic cup and around
      internalized phagosomes. To analyze the role of myosin IB in phagocytosis, a
      strain overexpressing the myosin IB gene was constructed. This strain synthesizes
      threefold more myosin IB than the wild-type strain. Challenge of the transfected
      cell line with erythrocytes showed that these amoebae were deficient in
      erythrophagocytosis mainly in the uptake step, suggesting a role for myosin IB in
      the pathogenic activity of a human parasite.

PMID- 10085255
TI  - Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1):
      heterodimerization with ARNT is not necessary for nuclear accumulation of HIF
      1alpha.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen
      homeostasis. HIF-1 consists of two subunits, HIF-1alpha and the aryl hydrocarbon
      receptor nuclear translocator (ARNT). Whereas hypoxia prevents proteasomal
      degradation of HIF-1alpha, ARNT expression is thought to be oxygen-independent.
      We and others previously showed that ARNT is indispensable for HIF-1 DNA-binding
      and transactivation function. Here, we have used ARNT-mutant mouse hepatoma and
      embryonic stem cells to examine the requirement of ARNT for accumulation and
      nuclear translocation of HIF-1alpha in hypoxia. As shown by immunofluorescence,
      HIF-1alpha accumulation in the nucleus of hypoxic cells was independent of the
      presence of ARNT, suggesting that nuclear translocation is intrinsic to HIF
      1alpha. Co-immunoprecipitation of HIF-1alpha together with ARNT could be
      performed in nuclear extracts but not in cytosolic fractions, implying that
      formation of the HIF-1 complex occurs in the nucleus. A proteasome inhibitor and
      a thiol-reducing agent could mimic hypoxia by inducing HIF-1alpha in the nucleus,
      indicating that escape from proteolytic degradation is sufficient for
      accumulation and nuclear translocation of HIF-1alpha. During biochemical
      separation, both HIF-1alpha and ARNT tend to leak from the nuclei in the absence
      of either subunit, suggesting that heterodimerization is required for stable
      association within the nuclear compartment. Nuclear stabilization of the
      heterodimer might also explain the hypoxically increased total cellular ARNT
      levels observed in some of the cell lines examined.

PMID- 10085256
TI  - Globular domains of agrin are functional units that collaborate to induce
      acetylcholine receptor clustering.
AB  - Agrin, an extracellular matrix protein involved in neuromuscular junction
      formation, directs clustering of postsynaptic molecules, including acetylcholine
      receptors (AChRs). This activity resides entirely in the C-terminal portion of
      the protein, which consists of three laminin-like globular domains (G-domains:
      G1, G2 and G3) and four EGF-like repeats. Additionally, alternate mRNA splicing
      yields G-domain variants G2(0,4) with 0- or 4-amino-acid inserts, and G3(0,
      8,11,19) with 0-, 8-, 11- or 19-amino-acid inserts. In order to better understand
      the contributions of individual domains and alternate splicing to agrin activity,
      single G-domains and covalently linked pairs of G-domains were expressed as
      soluble proteins and their AChR clustering activity measured on cultured C2
      myotubes. These analyses reveal the following: (1) While only G3(8) exhibits
      detectable activity by itself, all G-domains studied (G1, G2(0), G2(4), G3(0) and
      G3(8)) enhance G3(8) activity when physically linked to G3(8). This effect is
      most pronounced when G2(4) is linked to G3(8) and is independent of the order of
      the G-domains. (2) The deletion of EGF-like repeats enhances activity. (3)
      Increasing the physical separation between linked G1 and G3(8) domains produces a
      significant increase in activity; similar alterations to linked G2 and G3(8)
      domains are without effect. (4) Clusters induced by two concatenated G3(8)
      domains are significantly smaller than all other agrin forms studied. These data
      suggest that agrin G-domains are the functional units which interact
      independently of their specific organization to yield AChR clustering. G-domain
      synergism resulting in biological output could be due to physical interactions
      between G-domains or, alternatively, independent interactions of G-domains with
      cell surface receptors which require spatially localized coactivation for optimal
      signal transduction.

PMID- 10085257
TI  - Dcdc42 acts in TGF-beta signaling during Drosophila morphogenesis: distinct roles
      for the Drac1/JNK and Dcdc42/TGF-beta cascades in cytoskeletal regulation.
AB  - During Drosophila embryogenesis the two halves of the lateral epidermis migrate
      dorsally over a surface of flattened cells, the amnioserosa, and meet at the
      dorsal midline in order to form the continuous sheet of the larval epidermis.
      During this process of epithelial migration, known as dorsal closure, signaling
      from a Jun-amino-terminal-kinase cascade causes the production of the secreted
      transforming-growth-factor-beta-like ligand, Decapentaplegic. Binding of
      Decapentaplegic to the putative transforming-growth-factor-beta-like receptors
      Thickveins and Punt activates a transforming-growth-factor-beta-like pathway that
      is also required for dorsal closure. Mutations in genes involved in either the
      Jun-amino-terminal-kinase cascade or the transforming-growth-factor-beta-like
      signaling pathway can disrupt dorsal closure. Our findings show that although
      these pathways are linked they are not equivalent in function. Signaling by the
      Jun-amino-terminal-kinase cascade may be initiated by the small Ras-like GTPase
      Drac1 and acts to assemble the cytoskeleton and specify the identity of the first
      row of cells of the epidermis prior to the onset of dorsal closure. Signaling in
      the transforming-growth-factor-beta-like pathway is mediated by Dcdc42, and acts
      during the closure process to control the mechanics of the migration process,
      most likely via its putative effector kinase DPAK.

PMID- 10085258
TI  - E-cadherin binding prevents beta-catenin nuclear localization and beta
      catenin/LEF-1-mediated transactivation.
AB  - Beta-catenin is a multifunctional protein found in three cell compartments: the
      plasma membrane, the cytoplasm and the nucleus. The cell has developed elaborate
      ways of regulating the level and localization of beta-catenin to assure its
      specific function in each compartment. One aspect of this regulation is inherent
      in the structural organization of beta-catenin itself; most of its protein
      interacting motifs overlap so that interaction with one partner can block binding
      of another at the same time. Using recombinant proteins, we found that E-cadherin
      and lymphocyte-enhancer factor-1 (LEF-1) form mutually exclusive complexes with
      beta-catenin; the association of beta-catenin with LEF-1 was competed out by the
      E-cadherin cytoplasmic domain. Similarly, LEF-1 and adenomatous polyposis coli
      (APC) formed separate, mutually exclusive complexes with beta-catenin. In Wnt-1
      transfected C57MG cells, free beta-catenin accumulated and was able to associate
      with LEF-1. The absence of E-cadherin in E-cadherin-/- embryonic stem (ES) cells
      also led to an accumulation of free beta-catenin and its association with LEF-1,
      thereby mimicking Wnt signaling. beta-catenin/LEF-1-mediated transactivation in
      these cells was antagonized by transient expression of wild-type E-cadherin, but
      not of E-cadherin lacking the beta-catenin binding site. The potent ability of E
      cadherin to recruit beta-catenin to the cell membrane and prevent its nuclear
      localization and transactivation was also demonstrated using SW480 colon
      carcinoma cells.

PMID- 10085259
TI  - Polarized targeting of epithelial cell proteins in thyrocytes and MDCK cells.
AB  - Polarized trafficking signals may be interpreted differently in different cell
      types. In this study, we have compared the polarized trafficking of different
      proteins expressed endogenously in primary porcine thyroid epithelial cells to
      similar proteins expressed in MDCK cells. As in MDCK cells, NH4Cl treatment of
      filter-grown thyrocytes caused mis-sorted soluble proteins to exhibit enhanced
      secretion to the apical medium. In independent studies, thrombospondin 1 (a
      thyroid basolaterally secreted protein) was secreted basolaterally from MDCK
      cells. Likewise, the 5'-deiodinase (a thyroid basolateral membrane protein)
      encoded by the DIO1 gene was also distributed basolaterally in transfected MDCK
      cells. Consistent with previous reports, when the secretion of human growth
      hormone (an unglycosylated regulated secretory protein) was examined from
      transfected MDCK cells, the release was nonpolarized. However, transfected
      thyrocytes secreted growth hormone apically in a manner dependent upon zinc
      addition. Moreover, two additional regulated secretory proteins expressed in
      thyrocytes, thyroglobulin (the major endogenous glycoprotein) and parathyroid
      hormone (an unglycosylated protein expressed transiently), were secreted apically
      even in the absence of zinc. We hypothesize that while cellular mechanisms for
      interpreting polarity signals are generally similar between thyrocytes and MDCK
      cells, thyrocytes allow for specialized packaging of regulated secretory proteins
      for apical delivery, which does not require glycosylation but may involve
      availability of certain ions as well as appropriate intracellular
      compartmentation.

PMID- 10085260
TI  - The growth-related, translationally controlled protein P23 has properties of a
      tubulin binding protein and associates transiently with microtubules during the
      cell cycle.
AB  - The translationally controlled protein P23 was discovered by the early induction
      of its rate of synthesis after mitogenic stimulation of mouse fibroblasts. P23 is
      expressed in almost all mammalian tissues and it is highly conserved between
      animals, plants and yeast. Based on its amino acid sequence, P23 cannot be
      attributed to any known protein family, and its cellular function remains to be
      elucidated. Here, we present evidence that P23 has properties of a tubulin
      binding protein that associates with microtubules in a cell cycle-dependent
      manner. (1) P23 is a cytoplasmic protein that occurs in complexes of 100-150 kDa,
      and part of P23 can be immunoprecipitated from HeLa cell extracts with anti
      tubulin antibodies. (2) In immunolocalisation experiments we find P23 associated
      with microtubules during G1, S, G2 and early M phase of the cell cycle. At
      metaphase, P23 is also bound to the mitotic spindle, and it is detached from the
      spindle during metaphase-anaphase transition. (3) A GST-P23 fusion protein
      interacts with alpha- and beta-tubulin, and recombinant P23 binds to taxol
      stabilised microtubules in vitro. The tubulin binding domain of P23 was
      identified by mutational analysis; it shows similarity to part of the tubulin
      binding domain of the microtubule-associated protein MAP-1B. (4) Overexpression
      of P23 results in cell growth retardation and in alterations of cell morphology.
      Moreover, elevation of P23 levels leads to microtubule rearrangements and to an
      increase in microtubule mass and stability.

PMID- 10085261
TI  - Locomotory behaviour of epitheliocytes and fibroblasts on metallic grids.
AB  - Behaviour of epitheliocytes and fibroblasts on special discontinuous substrata
      (metallic grids with square openings of 45x45 microm2) was examined in order to
      compare the ability of these cells to spread in two mutually perpendicular
      directions and to stretch over the void spaces. Two cell types with typical
      fibroblastic morphology, the AGO 1523 line of human foreskin fibroblasts and
      secondary cultures of mouse embryo fibroblasts, and three cell types with typical
      epithelial morphology, primary mouse hepatocytes, the IAR-2 line of rat liver
      cells and the MDCK line of canine kidney epithelial cells (clone 20) were used.
      We also examined the epitheliocytes (MDCK cells, clone 20) transformed to
      fibroblast-like morphology by treatment with hepatocyte growth factor/scatter
      factor (HGF/SF). Time-lapse video microscopy, scanning electron microscopy and
      immunofluorescence microscopy were used to examine cell reorganizations at
      various stages of spreading. It was found that early stages of spreading of
      fibroblasts and epitheliocytes were similar: the cell spread along two bars,
      perpendicular to each other (bar and crossbar), with the formation of a small
      triangular lamellar cytoplasm stretched over the opening. Later central parts of
      the bodies of the fibroblasts retracted from the bars so that the cells remained
      attached only by their polar lamellae. Successive expansions and partial
      retractions of these lamellae led to elongation of the cell body crossing several
      openings of the grid. Epitheliocytes, in contrast to fibroblasts, at the late
      stages of spreading did not retract their bodies and did not contract polar
      lamellae. As a result, their central lamellae stretched progressively over the
      openings. As a result of the treatment of MDCK epitheliocytes with HGF/SF the
      behaviour of the cells on the grids became similar to that of fibroblasts. It is
      suggested that these distinct spreading patterns of epitheliocytes and
      fibroblasts are due to the type-specific differences in the actin-myosin cortex.
      Experiments with microtubule-specific drugs, colcemid and taxol, indicate that
      the organization of this cortex is under microtubular control.

PMID- 10085262
TI  - The case for light-dependent magnetic orientation in animals 
AB  - Light-dependent models of magnetoreception have been proposed which involve an
      interaction between the magnetic field and either magnetite particles located
      within a photoreceptor or excited states of photopigment molecules. Consistent
      with a photoreceptor-based magnetic compass mechanism, magnetic orientation
      responses in salamanders, flies and birds have been shown to be affected by the
      wavelength of light. In birds and flies, it is unclear whether the effects of
      light on magnetic orientation are due to a direct effect on a magnetoreception
      system or to a nonspecific (e.g. motivational) effect of light on orientation
      behavior. Evidence from shoreward-orienting salamanders, however, demonstrates
      that salamanders perceive a 90 degrees counterclockwise shift in the direction of
      the magnetic field under long-wavelength (>=500 nm) light. A simple physiological
      model based on the antagonistic interaction between two magnetically sensitive
      spectral mechanisms suggests one possible way in which the wavelength-dependent
      effects of light on the salamander's magnetic compass response might arise.
      Assuming that the wavelength-dependent characteristics of the avian magnetic
      response can be attributed to an underlying magnetoreception system, we discuss
      several hypotheses attempting to resolve the differences observed in the
      wavelength-dependent effects of light on magnetic orientation in birds and
      salamanders. By considering the evidence in the context of photoreceptor- and non
      photoreceptor-based mechanisms for magnetoreception, we hope to encourage future
      studies designed to distinguish between alternative hypotheses concerning the
      influence of light on magnetoreception.

PMID- 10085263
TI  - Hearing with the mouthparts: behavioural responses and the structural basis of
      ultrasound perception in acherontiine hawkmoths 
AB  - In contrast to previous assumptions, mouthparts form hearing organs not only in
      choerocampine hawkmoths but also in some distantly related acherontiine hawkmoth
      species. Four of the six acherontiine species studied revealed responses to
      ultrasonic sounds when stimulated during tethered flight. The responses included
      changes in flight speed and non-directional turns. Individuals from two species
      also responded by emitting sound. The minimum thresholds of the flight pattern
      changes were approximately 70 dB in all species studied, with species-specific
      best frequencies between 30 and 70 kHz. Some acherontiine species also move their
      tongue in a stereotyped way when stimulated acoustically. The activity of the
      muscles involved in this tongue reflex was characterized in the present study and
      used in combination with ablation experiments to localize the hearing organ.
      These experiments revealed auditory functions of the labial palps and the labral
      pilifers similar to those found in Choerocampina. The palp contributes a 20-25 dB
      rise in sensitivity, whereas the pilifer appears to contain the sensory organ.
      Structural differences suggest a convergent evolution of hearing in hawkmoths: in
      the place of the swollen palps of Choerocampina, acherontiine species capable of
      hearing possess a scale-plate of the palps that interacts with an articulating
      pilifer, while this modification is absent in closely related non-hearing
      species.

PMID- 10085264
TI  - Structure, fluorescent properties and proposed function in phototaxis of the
      stigma apparatus in the ciliate chlamydodon mnemosyne 
AB  - Chlamydodon mnemosyne, a brackish-water ciliate which feeds on cyanobacteria, is
      capable of sensing the direction of light. Cells are negatively phototactic in
      the well-fed state and tend to swim towards the light source when mildly starved.
      Severely starved cells normally fail to show phototactic responses. An
      autofluorescent substance, which is present in all life cycle stages, occurs in,
      or immediately beneath, the plasma membrane of this ciliate. It is located in the
      anterior left side of a cell, in the same region where mildly starved cells
      accumulate small orange globules that form a structure known as the stigma. The
      diameter of the whole area where the autofluorescent substance is located appears
      to be smaller than the stigma; typically, it consists of two rows of blue-green
      fluorescence, each row subdivided into 5-10 squares. Since the blue-green
      autofluorescence is excited by both blue (450-490 nm) and near-ultraviolet (340
      380 nm) light, it possibly originates from flavin- and/or pterin-like molecules.
      We suggest that the autofluorescent substance located in or beneath the plasma
      membrane of Chlamydodon mnemosyne acts as a photoreceptor pigment in phototaxis
      and that photo-orientation of this ciliate is triggered by a combined mechanism
      involving the photoreceptor and either the stigma or a number of light-absorbing
      food vacuoles as a shading device.

PMID- 10085265
TI  - Differential expression of mitochondrial genes between queens and workers during
      caste determination in the honeybee Apis mellifera.
AB  - The nourishment received by female honeybee larvae determines their
      differentiation into queens or workers. In this study, we report the first
      molecular analysis of differences that occur between queens and workers during
      the caste-determination process. RNA-differential display experiments identified
      a clone that encodes for a gene that is homologous to the nuclear-encoded
      mitochondrial translation initiation factor (AmIF-2mt). Semi-quantitative
      analysis by reverse transcriptase/polymerase chain reaction (RT-PCR) throughout
      honeybee development detected a higher level of expression of this gene in queen
      larvae than in worker larvae. Analysis of two other genes encoding mitochondrial
      proteins, cytochrome oxidase subunit 1 (COX-1; mitochondrial-encoded) and
      cytochrome c (cyt c; nuclear-encoded) also showed differential expression of
      these two genes between queens and workers. In particular, the cyt c transcript
      is more abundant in queen larvae and throughout the metamorphosis of the queen.
      These results indicate that the higher respiratory rate previously documented in
      queen larvae is accomplished through a higher level of expression of both nuclear
      and mitochondrial-encoded genes for mitochondrial proteins.

PMID- 10085266
TI  - Lack of glomerular intermittency in the river lamprey lampetra fluviatilis
      acclimated to sea water and following acute transfer to iso-osmotic brackish
      water 
AB  - Previous studies have suggested that in the lamprey Lampetra fluviatilis, in
      contrast to teleost fish, all glomeruli are actively filtering. In the present
      study, we have applied the ferrocyanide technique to obtain more definitive
      values for the population of filtering nephrons in the lamprey under conditions
      of high (in fresh water) and low (in sea water) glomerular filtration rate (GFR)
      and when the branchial osmotic gradient was eliminated by acute transfer of
      freshwater lampreys to iso-osmotic brackish water. These studies demonstrated
      that the renal antidiuresis in lampreys acclimated to full-strength sea water
      does not involve any reduction in the filtering population of glomeruli. Transfer
      to brackish water significantly reduced GFR and thereby urine flow rate (287+/-23
      ml kg-1 24 h-1 in fresh water; 6.9+/-2.5 ml kg-1 24 h-1 in brackish water). In
      four of the eight fish examined, 100 % of glomeruli remained filtering; in the
      other four fish, non-filtering glomeruli occurred in patches along the kidney,
      always associated with an absence of vascular perfusion, which implies possible
      endocrine/neural control of vascular tone. The numbers of non-filtering glomeruli
      were always small, and these glomeruli do not appear to make a major contribution
      to the overall decline in urine output. The results provide firm evidence that
      although lampreys, like teleosts, show considerable variations in urine output,
      the renal mechanisms by which lampreys and the teleosts achieve this differ
      fundamentally, with glomerular intermittency playing little or no part in the
      lamprey.

PMID- 10085267
TI  - Secretion of primary urine by glomeruli of the hagfish kidney 
AB  - Adrenaline and noradrenaline increased the perfusion pressure (Pperf) and single
      glomerulus filtration rate (SGFR) of perfused hagfish glomeruli. Small amounts
      (0.1 % or 0.5 %) of bovine serum albumin (BSA) in perfusion fluids containing
      Ficoll 70 did not diminish the loss of colloid from hagfish glomerular
      capillaries as has been reported for other perfused capillaries. However,
      replacement of Ficoll 70 with an osmotically equivalent amount (3 %) of BSA
      appreciably reduced colloid loss. It was concluded that adrenaline and colloids
      enhanced flow through the urine-forming capillaries. Whereas adrenaline elevated
      the SGFR, colloid lowered the SGFR probably by a direct effect on the fluid
      permeability of the capillary walls. The flow-enhancing effect of adrenaline was
      used to ensure the exposure of urine-forming capillaries to two inhibitors of
      active fluid transport, ouabain and 2,4-dinitrophenol (DNP). Both substances
      lowered the single glomerulus filtration fraction (SGFF), probably by affecting a
      fluid secretion mechanism. In addition, DNP diminished the flow-enhancing effect
      of adrenaline. This study provides relatively unequivocal evidence that fluid
      secretion underlies the formation of primary urine by the hagfish.

PMID- 10085268
TI  - Venom of a parasitoid wasp induces prolonged grooming in the cockroach 
AB  - The parasitoid wasp Ampulex compressa hunts cockroaches Periplaneta americana,
      stinging them first in the thorax and then in the head, the sting penetrating
      towards the subesophageal ganglion. After being stung the cockroach grooms almost
      continuously for approximately 30 min, performing all the normal components of
      grooming behavior. This excessive grooming is only seen after the head sting and
      cannot be attributed to stress, to contamination of the body surface or to
      systemic or peripheral effects. This suggests that the venom is activating a
      neural network for grooming. We suggest that the venom induces prolonged grooming
      by stimulating dopamine receptors in the cockroach, for the following reasons.
      (1) Reserpine, which causes massive release of monoamines, induces excessive
      grooming. (2) Dopamine injected into the hemocoel also induces excessive grooming
      and is significantly more effective than octopamine or serotonin. In addition,
      the dopamine agonist SKF 82958 induces excessive grooming when injected directly
      into the subesophageal ganglion. (3) Injection of the dopamine antagonist
      flupenthixol greatly reduces venom-induced grooming. (4) Dopamine, or a dopamine
      like substance, is present in the venom.

PMID- 10085269
TI  - CO2 excretion and postcapillary pH equilibration in blood-perfused turtle lungs 
AB  - Turtles possess a significant postcapillary CO2 partial pressure (PCO2)
      disequilibrium between arterial blood and alveolar gas. There are several
      possible explanations for this blood disequilibrium including a slow rate of
      erythrocyte physiological anion shift (Cl-/HCO3- exchange) or inaccessibility of
      plasma HCO3- to red blood cell or pulmonary carbonic anhydrase. The present study
      characterized the contribution of erythrocyte anion exchange and pulmonary and
      erythrocyte carbonic anhydrase to CO2 excretion and, hence, to postcapillary CO2
      HCO3--H+ equilibration in blood-perfused turtle (Pseudemys scripta) lungs. Turtle
      lungs perfused in situ with red cell suspensions containing inhibitors of
      erythrocyte anion exchange and/or pulmonary and red cell carbonic anhydrase
      produced significant postcapillary blood PCO2 and pH disequilibria, while no
      disequilibria were measured when lungs were perfused with control red cell
      suspensions. Erythrocyte anion exchange and pulmonary intravascular carbonic
      anhydrase contributed 11 % and 9 %, respectively, to CO2 excretion during single
      pass perfusion, whereas red cell and pulmonary carbonic anhydrase contributed 32
      % to the measured CO2 excretion. The lack of a measurable PCO2 disequilibrium
      during perfusion with control erythrocyte suspensions in this study suggests that
      alternative mechanisms may be responsible for the arterial-lung PCO2
      disequilibrium measured during breathing or diving episodes in turtles.

PMID- 10085270
TI  - Ionic mechanisms of phototransduction in photoreceptor cells from the epistellar
      body of the octopus eledone cirrhosa 
AB  - Intracellular recordings were made from extraocular photoreceptor cells within
      isolated epistellar bodies of the lesser or northern octopus Eledone cirrhosa.
      The cells had resting potentials around -41+/-5 mV (mean +/- s.d., N=60) and
      showed light-flash-induced membrane depolarisation. The evoked response to a
      brief light flash consisted of a transient peak depolarisation, followed by a
      plateau component. The magnitude of the light-induced peak depolarisation
      response was decreased by bathing the epistellar body in artificial sea water
      (ASW) low in Na+, where choline+ replaced Na+, or by passing steady depolarising
      current. Replacement of external Na+ by Li+ had no effect on the light-stimulated
      response. The external application of the Na+ channel blocker tetrodotoxin (3
      micromol l-1) increased the light-evoked response, but this was accompanied by a
      loss of action potential activity. The amplitude and duration of the response to
      a light flash was increased by bathing the epistellar body in ASW low in Ca2+, or
      in ASW containing 10 mmol l-1 Co2+, and after intracellular microinjection of the
      Ca2+ buffer EGTA. Intracellular microinjection of Ca2+ or inositol 1,4,5
      trisphosphate, or external application of the phospholipase C inhibitor U-73122,
      had no apparent effect on the light-evoked response. These results are consistent
      with the interpretation that (1) the majority of the light-induced inward current
      is carried by Na+, probably via a non-selective cation channel, and (2) an
      increase in the intracellular free Ca2+ concentration, mediated by the
      phototransduction process, is involved in regulating the light-induced inward
      photocurrent and thus, in effect, determines the amplitude, time course and
      sensitivity of the receptor potential.

PMID- 10085271
TI  - Responsiveness of gill Na+/K+-ATPase to cortisol is related to gill
      corticosteroid receptor concentration in juvenile rainbow trout 
AB  - A positive relationship between receptor concentration and tissue responsiveness
      is an often-assumed and rarely tested principle in endocrinology. In salmonids,
      seasonal changes in levels of plasma cortisol and gill corticosteroid receptors
      (CRs) during the spring indicate a potential role for this hormone in the parr
      smolt transformation. It is not known whether these seasonal changes result in
      alterations in gill responsiveness to cortisol. The relationship between CR
      concentration and tissue responsiveness was, therefore, examined in the gills of
      juvenile rainbow trout (Oncorhynchus mykiss). Gill CR concentration (Bmax) and
      affinity (Kd) were assessed using a radioligand binding assay with the synthetic
      glucocorticoid triamcinolone acetonide. Gill responsiveness to cortisol was
      quantified by measuring in vitro Na+/K+-ATPase activity. Gill CR concentration
      was manipulated by stress or hormonal treatments. Repeated handling stresses
      resulted in a significant reduction in CR numbers. The decrease in CR Bmax
      corresponded to a reduction in gill responsiveness to cortisol. Triiodothyronine,
      but not growth hormone, treatment was found to increase CR Bmax significantly.
      The increase in CR numbers was correlated with a marked increase in gill
      responsiveness to cortisol. A significant positive linear relationship exists
      between the in vitro gill Na+/K+-ATPase activity response to cortisol and CR Bmax
      (r2=0.614, P<0.001). We have demonstrated that binding sites for cortisol in the
      gills of rainbow trout have high affinity, high specificity and saturable binding
      and that the number of binding sites is correlated with the tissue response to
      cortisol.

PMID- 10085272
TI  - Inhibitory and excitatory responses of olfactory receptor neurons of xenopus
      laevis tadpoles to stimulation with amino acids 
AB  - Recordings were made from olfactory receptor neurons of Xenopus laevis tadpoles
      using the patch-clamp technique to investigate the responses of these cells to
      odorants. Four amino acids (glutamate, methionine, arginine and alanine) both
      individually and as a mixture were used as stimuli. Of the 156 olfactory neurons
      tested, 43 showed a response to at least one of the stimuli. Of the cells tested,
      19 % responded to glutamate, 16 % to methionine, 12 % to arginine and 10 % to
      alanine. Each amino acid was able to induce both excitatory and inhibitory
      responses, although these occurred in different cells. Each amino acid produced
      approximately equal numbers of inhibitory and excitatory responses. Inhibitory
      responses could best be observed in the perforated-patch configuration using
      gramicidin as an ionophore and a recording configuration that is a current-clamp
      for fast signals and a voltage-clamp for slow signals. The diversity of the
      odorant responses, in particular the existence of excitatory and inhibitory
      responses, is not consistent with a single transduction pathway in olfactory
      neurons of Xenopus laevis tadpoles.

PMID- 10085273
TI  - Vasodilation of swimbladder vessels in the european eel (Anguilla anguilla)
      induced by vasoactive intestinal polypeptide, nitric oxide, adenosine and protons
AB  - The effects of &bgr;-adrenergic stimulation, vasoactive intestinal polypeptide
      (VIP), adenosine, the nitric oxide (NO)-releasing agent sodium nitroprusside and
      of metabolic end-products of gas gland cell metabolism on swimbladder blood flow
      were investigated using saline- or blood-perfused swimbladder preparations of the
      freshwater European eel Anguilla anguilla. While &bgr;-adrenergic vasodilation
      was not detectable, a bolus injection of adenosine (100 microl, 10(-)7 mol l-1)
      and application of VIP (10(-)7 mol kg-1) caused a significant decrease in
      perfusion pressure in saline-perfused swimbladder preparations.
      Immunohistochemical analysis revealed the presence of VIP-immunoreactive nerve
      fibres in the swimbladder artery and in the swimbladder vein (seawater-adapted
      eels were used for immunohistochemical studies). Application of sodium
      nitroprusside also elicited a small, but significant, decrease in perfusion
      pressure in saline-perfused swimbladder preparations, while preincubation of
      swimbladder tissue with N(&ohgr;)nitro-l-arginine, a non-selective inhibitor of
      nitric oxide synthase, significantly enhanced the flow-induced increase in
      perfusion pressure. Lactate, the major metabolic end-product of gas gland cell
      metabolism, had no effect on perfusion pressure. In contrast, an increase in
      proton concentration in both saline- and blood-perfused preparations induced a
      vasodilation, as indicated by a significant decrease in perfusion pressure. The
      results demonstrate that VIP, NO, adenosine and protons may induce a vasodilation
      of swimbladder blood vessels. None of these effects, however, compares in time
      span with the previously described immediate, short-lasting vasodilation of
      swimbladder vessels elicited by pulse stimulation of the vagus nerve.

PMID- 10085274
TI  - Interleukin-10: effects on phagocytosis and adhesion molecule expression of
      granulocytes and monocytes in a comparison with prednisolone.
AB  - Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive
      properties. The potential therapeutic benefit may be compromised by the down
      regulation of the non-specific immune system and an increased risk of infection.
      We studied the effects of IL-10 on important functions of native and granulocyte
      macrophage colony-stimulating factor (GM-CSF) activated neutrophils and
      monocytes, namely phagocytosis and membrane expression of the beta superset2
      integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to
      simulate the in vivo situation closely, we used whole blood flowcytometric
      assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of
      prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive
      drug which is known to impair phagocyte function. - Incubation with IL-10 for
      three hours significantly attenuated the ability of neutrophils to phagocytose
      E.coli, particularly in lower concentrations. On the other hand, high IL-10
      concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis.
      Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes
      was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml
      and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of
      monocyte receptor expression. Neutrophil adhesion molecule expression was not
      affected. Prednisolone suppressed the phagocytosis of both cell types in a dose
      dependent fashion but hardly altered the receptor numbers. Our study indicates
      that IL-10 can behave as a de-activator as well as an activator on the non
      specific immune system, depending on the cell type and the concentration.

PMID- 10085275
TI  - Cytokine profile of HIV-positive Kaposi's sarcoma derived cells in vitro.
AB  - Kaposi's sarcoma (KS) is the most frequent neoplastic complication observed in
      HIV-infected patients. Cutaneous KS is the most common manifestation but visceral
      and lymph node involvement may occur. HIV-infection does not only lead to a
      decrease of certain cell types (CD4 T-lymphocytes), but also modifies the
      function of non-infected cells such as B-lymphocytes and NK-cells by upregulating
      cytokine release of IL-1, IL-6, GM-CSF, IFN-gamma and TNF-alpha. These
      multifunctional mediators show both autocrine and paracrine proliferative effects
      on normal endothelial cells and AIDS-related KS-cells. Using ELISA-, RIA- and
      IRMA-techniques we analysed the influence of seven cytokines (IL-1beta, IL-6, TNF
      alpha, GM-CSF, IFN-alpha, IFN-beta, IFN-gamma) and the soluble IL-2 receptor (sIL
      2R) on the growth of eight different KS-derived cell lines compared with eight
      fibroblast cell lines, established from skin biopsies of HIV-positive
      individuals. Furthermore, we analysed the dose-dependent effect of the above
      mentioned cytokines on KS-derived cells in vitro. The KS-derived cell culture
      medium demonstrated significantly higher concentrations than the fibroblast cell
      lines in view of the following cytokines: sIL-2R, IL-1beta, IL-6, TNF-alpha, GM
      CSF, IFN-gamma (p<0.05). The most pronounced differences between KS-cells and
      fibroblasts were observed for IL-1beta and IFN-gamma. The antiproliferative
      effect of IFN-beta and IFN-gamma began at a concentration of 20 and 50 IU/ml,
      respectively, whereas for IFN-alpha an antiproliferative effect was observed at a
      concentration of 100 U/ml. Furthermore we observed a proliferative effect in low
      concentrations (2-5 IU/ml) of IFN-gamma in our in vitro model

PMID- 10085276
TI  - Single daily doses of saquinavir achieve HIV-inhibitory concentrations when
      combined with baby-dose ritonavir.
AB  - Dual protease inhibitor (PI) therapy has been established either in order to
      increase plasma concentrations of one PI or to combine synergistic effects of two
      PI's on viral load. Studies with saquinavir (SQV) and small doses of ritonavir
      (RTV) as well as experiences from our therapeutic drug monitoring suggest that
      single daily doses may result in sufficient SQV serum levels throughout an
      interval of 24 h. A controlled, randomized trial with 20 healthy men was
      conducted for the comparison of serum levels with 1600 mg SQV (group 1) or 1600
      mg SQV/200 mg RTV (group 2). The dosages were selected in order to use RTV as an
      inhibitor of cytochrome P450 3A4 and SQV as protease inhibitor. The volunteers
      received single daily doses following a standardized breakfast on 3 consecutive
      days. Serum samples were analyzed for SQV and RTV employing LC-tandem mass
      spectrometry. The minimum concentration of saquinavir after 24 hours, the AUC,
      the maximum concentration and the serum half-lives on day 3 served as target
      parameters. The minimum SQV concentration amounted to 469.4 ng/ml, when combined
      with RTV and proved to be significantly higher (p <0.05) than the corresponding
      concentration with SQV alone (127.3 ng/ml). The SQV maximum concentration was
      raised approximately 6fold and the AUC 9fold when RTV was coadministered. In
      combination with 200 mg of RTV the predominant elimination half-life of SQV
      increased from 2.6 to 6.45 hours. These data prove that under single daily doses
      of 1600 mg SQV/200 mg RTV HIV-inhibitory concentrations of SQV can be achieved
      for 24 hours. Due to the high variability of the concentrations, which can be
      seen with all PI s, we recommend continuous therapeutic drug monitoring of serum
      trough levels.

PMID- 10085277
TI  - Proliferating cell nuclear antigen expression grossly over-estimates cellular
      proliferation in cardiac myxomas.
AB  - AIMS: Myxomas are thought to be slowly growing benign neoplasms. Presentation is
      often due to embolic phenomena, though rapid increase in size is sometimes seen.
      Such an increase may be due to proliferation of cellular components, an increase
      in matrix due to synthesis or oedema, haemorrhage into the lesion, or the
      addition of surface thrombus. Routine microscopy suggests a low proliferation
      rate. The aim of this study was to investigate cellular proliferation, and to
      assess its contribution to tumour growth. METHODS: The antibodies JC1, Ki67,
      PC10, and MIB1 were used to make an immunohistochemical assessment of
      proliferation in five cases of cardiac myxoma. RESULTS: A significant difference
      was seen between number and type of cells stained with PC10 and the other
      markers. Whilst PC10 stained the nuclei of most (60 - 95%) endothelial and
      stromal cells in all cases, the other markers stained far fewer cells (up to 5%).
      All markers stained varying numbers of lymphoid cells. CONCLUSIONS: Proliferation
      in cardiac myxomas is unlikely to be rapid. The widespread positivity for PC10
      suggests that PCNA is not a reliable marker in such tissues. Clinical cases in
      which myxomas have grown rapidly are probably due to changes in intercellular
      matrix rather than cellular proliferation.

PMID- 10085278
TI  - Trends in allergies among children in a region of former East Germany between
      1992-1993 and 1995-1996.
AB  - A lower prevalence of asthma and allergies has been reported among children and
      adults living in the area of former East Germany compared with those living in
      West Germany. After German reunification in 1990, the East German population
      rapidly adopted a western lifestyle. Therefore, this study examined if the
      prevalence rates of allergic diseases, symptoms, and sensitisation and asthma
      have increased among East German children since German reunification. - Children
      aged 5 to 7 years living in the region of Sachsen-Anhalt, East Germany were
      examined in two cross-sectional studies during 1992-93 (n = 769, response rate
      84.0%) and 1995-96 (n = 725, response rate 74.6%). Sensitisation was assessed by
      specific immunoglobulin E measurements against five common aeroallergens using
      the CAP-FEIA technique. After adjustment for sex, parental education, season of
      examination, day care attendance, breast feeding, environmental tobacco smoke
      exposure, cat dander exposure, and several indoor factors, an increase in the
      prevalence of self-reported, physician-diagnosed allergies (OR 1.44, 95% CI 1.01
      2. 06), but not in allergic sensitisation (OR 0.85, 95% CI 0.62-1.16) was found.
      The only evidence of an increase in allergies of the self-reported increase in
      the prevalence of physician-diagnosed allergies is likely due to changes in
      physician diagnostic patterns and the heightened public awareness of allergic
      diseases. - In conclusion, there were no significant changes in the prevalence of
      asthma, allergic rhinitis, or self-reported symptoms of allergic diseases.

PMID- 10085279
TI  - Late auditory evoked potentials (P300) do not discriminate between subgroups of
      alcohol-dependent patients defined by family history and antisocial personality
      traits.
AB  - Alcohol dependent patients with a family history of alcoholism and with
      antisocial personality traits were supposed to have frontal brain dysfunction.
      Late evoked potentials may be useful to discriminate these patients from patients
      without family history or antisocial behavior. We investigated 56 abstinent
      patients hypothesizing that four subgroups of abstinent alcoholics with regard to
      family history (FHP: family history positive, FHN: family history negative) and
      antisocial behavior (ASP: antisocial traits present, ASN: antisocial traits not
      present) would exhibit differences in P300, particularly when recorded by frontal
      electrodes. FHP/ASP patients were expected to show the lowest P300 amplitudes in
      frontal electrode sites. Beside single electrode recordings, a new method in
      analyzing P300 scalp data by dipole source analysis (BESA: Brain electric signal
      analysis) was used. No difference in the P300 values was observed between the
      FHP/FHN and ASP/ASN groups. Similar results were found by analyzing ASP/ASN and
      FHP/FHN groups separately. The findings of single electrode recordings were
      consistent with BESA-dipole results. In conclusion, auditory P300 had a low
      discriminative power with regards to subgroups of inpatient alcoholics defined by
      family history and antisocial personality traits. Reasons for the negative
      findings in this study are discussed.

PMID- 10085280
TI  - Cases of HIV-associated characteristic periodontal diseases.
AB  - In the course of infection by the Human Immunodeficiency Virus (HIV) typical
      changes of inflammatory periodontal diseases can arise. The prevalence of these
      illnesses may be up to 5%. The HIV-associated periodontal diseases include linear
      gingival erythema (LGE), necrotizing ulcerative gingivitis (NUG) and necrotizing
      ulcerative periodontitis (NUP). The necrotizing forms appear particularly in
      severe or advanced immunosuppression. It can be safely assumed that the HIV
      infection and the resulting immunological defects are responsible for these
      severe forms of destruction of the periodontal tissue. Periodontal therapy
      consists in the removal of necrotic tissues and removal of soft and hard plaque
      deposits. This is supported by a chlorhexidine digluconate mouthrinse and
      antibiotics. In the interest of further prophylactics a strict system of recall
      appointments is recommended.

PMID- 10085281
TI  - Effects of topical honey on post-operative wound infections due to gram positive
      and gram negative bacteria following caesarean sections and hysterectomies.
AB  - The possible therapeutic effect of topical crude undiluted honey in the treatment
      of severe acute postoperative wound infections was studied. Fifty patients having
      postoperative wound infections following caesarean sections or total abdominal
      hysterectomies with gram positive or gram negative bacterial infections were
      allocated in two groups. Twenty-six patients (group A) were treated with 12
      hourly application of crude honey and 24 patients (group B) were treated with
      local antiseptics: spirit (70% Ethanol) and povidone-iodine. Both groups received
      systemic antibiotics according to culture and sensitivity. Results showed that
      eradication of bacterial infections was obtained after 6 +/- 1.9 days (mean +/-
      SD) in group A and after 14.8 +/- 4.2 days in group B (p <0.05). Period for
      antibiotics use was 6.88 +/- 1.7 days in-group A and 15.45 +/- 4. 37 in-group B
      (p <0.05). Complete wound healing was evident after 10. 73 +/- 2.5 days in group
      A and after 22.04 +/- 7.33 in group B (p <0. 05). Size of postoperative scar was
      3.62 +/- 1.4 mm after using topical honey and was 8.62 +/- 3.8 mm after local
      antiseptics (p <0. 05). The mean hospital stay was 9.36 +/- 1.8 days in group A
      and 19. 91 +/- 7.35 days in group B (p <0.05). After using honey, 22/26 patients
      (84.4%) showed complete wound healing without wound disruption or need for re
      suturing and only 4 patients showed mild dehiscence. In group B, 12/24 patients
      (50%) showed complete wound healing and 12 patients showed wound dehiscence, six
      of them needed re-suturing under general anesthesia. We concluded that topical
      application of crude undiluted honey could (1) faster eradication of bacterial
      infections, (2) reduce period of antibiotic use and hospital stay, (3) accelerate
      wound healing, (4) prevent wound dehiscence and need for re-suturing and (5)
      result in minimal scar formation.

PMID- 10085282
TI  - Formin' the connection between microtubules and the cell cortex.

PMID- 10085283
TI  - Direct imaging of DNA in living cells reveals the dynamics of chromosome
      formation.
AB  - Individual chromosomes are not directly visible within the interphase nuclei of
      most somatic cells; they can only be seen during mitosis. We have developed a
      method that allows DNA strands to be observed directly in living cells, and we
      use it to analyze how mitotic chromosomes form. A fluorescent analogue (e.g., Cy5
      dUTP) of the natural precursor, thymidine triphosphate, is introduced into cells,
      which are then grown on the heated stage of a confocal microscope. The analogue
      is incorporated by the endogenous enzymes into DNA. As the mechanisms for
      recognizing and removing the unusual residues do not prevent subsequent progress
      around the cell cycle, the now fluorescent DNA strands can be followed as they
      assemble into chromosomes, and segregate to daughters and granddaughters. Movies
      of such strands in living cells suggest that chromosome axes follow simple
      recognizable paths through their territories during G2 phase, and that late
      replicating regions maintain their relative positions as prophase chromosomes
      form. Quantitative analysis confirms that individual regions move little during
      this stage of chromosome condensation. As a result, the gross structure of an
      interphase chromosome territory is directly related to that of the prophase
      chromosome.

PMID- 10085284
TI  - The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix
      protein involved in 60S ribosomal subunit assembly.
AB  - p27(BBP/eIF6) is an evolutionarily conserved protein that was originally
      identified as p27(BBP), an interactor of the cytoplasmic domain of integrin beta4
      and, independently, as the putative translation initiation factor eIF6. To
      establish the in vivo function of p27(BBP/eIF6), its topographical distribution
      was investigated in mammalian cells and the effects of disrupting the
      corresponding gene was studied in the budding yeast, Saccharomyces cerevisiae. In
      epithelial cells containing beta4 integrin, p27(BBP/eIF6) is present in the
      cytoplasm and enriched at hemidesmosomes with a pattern similar to that of beta4
      integrin. Surprisingly, in the absence and in the presence of the beta4 integrin
      subunit, p27(BBP/eIF6) is in the nucleolus and associated with the nuclear
      matrix. Deletion of the IIH S. cerevisiae gene, encoding the yeast p27(BBP/eIF6)
      homologue, is lethal, and depletion of the corresponding gene product is
      associated with a dramatic decrease of the level of free ribosomal 60S subunit.
      Furthermore, human p27(BBP/eIF6) can rescue the lethal effect of the iihDelta
      yeast mutation. The data obtained in vivo suggest an evolutionarily conserved
      function of p27(BBP/eIF6) in ribosome biogenesis or assembly rather than in
      translation. A further function related to the beta4 integrin subunit may have
      evolved specifically in higher eukaryotic cells.

PMID- 10085285
TI  - Proteins connecting the nuclear pore complex with the nuclear interior.
AB  - While much has been learned in recent years about the movement of soluble
      transport factors across the nuclear pore complex (NPC), comparatively little is
      known about intranuclear trafficking. We isolated the previously identified
      Saccharomyces protein Mlp1p (myosin-like protein) by an assay designed to find
      nuclear envelope (NE) associated proteins that are not nucleoporins. We localized
      both Mlp1p and a closely related protein that we termed Mlp2p to filamentous
      structures stretching from the nucleoplasmic face of the NE into the nucleoplasm,
      similar to the homologous vertebrate and Drosophila Tpr proteins. Mlp1p can be
      imported into the nucleus by virtue of a nuclear localization sequence (NLS)
      within its COOH-terminal domain. Overexpression experiments indicate that Mlp1p
      can form large structures within the nucleus which exclude chromatin but appear
      highly permeable to proteins. Remarkably, cells harboring a double deletion of
      MLP1 and MLP2 were viable, although they showed a slower net rate of active
      nuclear import and faster passive efflux of a reporter protein. Our data indicate
      that the Tpr homologues are not merely NPC-associated proteins but that they can
      be part of NPC-independent, peripheral intranuclear structures. In addition, we
      suggest that the Tpr filaments could provide chromatin-free conduits or tracks to
      guide the efficient translocation of macromolecules between the nucleoplasm and
      the NPC.

PMID- 10085286
TI  - Calreticulin is essential for cardiac development.
AB  - Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic
      reticulum lumen, which has been implicated in many diverse functions including:
      regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid
      mediated gene regulation, and cell adhesion. To understand the physiological
      function of calreticulin we used gene targeting to create a knockout mouse for
      calreticulin. Mice homozygous for the calreticulin gene disruption developed
      omphalocele (failure of absorption of the umbilical hernia) and showed a marked
      decrease in ventricular wall thickness and deep intertrabecular recesses in the
      ventricular walls. Transgenic mice expressing a green fluorescent protein
      reporter gene under the control of the calreticulin promoter were used to show
      that the calreticulin gene is highly activated in the cardiovascular system
      during the early stages of cardiac development. Calreticulin protein is also
      highly expressed in the developing heart, but it is only a minor component of the
      mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was
      inhibited in crt-/- cells, suggesting that calreticulin plays a role in Ca2+
      homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import
      of nuclear factor of activated T cell (NF-AT3) transcription factor indicating
      that calreticulin plays a role in cardiac development as a component of the
      Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.

PMID- 10085287
TI  - SNARE membrane trafficking dynamics in vivo.
AB  - The ER/Golgi soluble NSF attachment protein receptor (SNARE) membrin, rsec22b,
      and rbet1 are enriched in approximately 1-micrometer cytoplasmic structures that
      lie very close to the ER. These appear to be ER exit sites since secretory cargo
      concentrates in and exits from these structures. rsec22b and rbet1 fused to
      fluorescent proteins are enriched at approximately 1-micrometer ER exit sites
      that remained more or less stationary, but periodically emitted streaks of
      fluorescence that traveled generally in the direction of the Golgi complex. These
      exit sites were reused and subsequent tubules or streams of vesicles followed
      similar trajectories. Fluorescent membrin- enriched approximately 1-micrometer
      peripheral structures were more mobile and appeared to translocate through the
      cytoplasm back and forth, between the periphery and the Golgi area. These mobile
      structures could serve to collect secretory cargo by fusing with ER-derived
      vesicles and ferrying the cargo to the Golgi. The post-Golgi SNAREs, syntaxin 6
      and syntaxin 13, when fused to fluorescent proteins each displayed characteristic
      patterns of movement. However, syntaxin 13 was the only SNARE whose life cycle
      appeared to involve interactions with the plasma membrane. These studies reveal
      the in vivo spatiotemporal dynamics of SNARE proteins and provide new insight
      into their roles in membrane trafficking.

PMID- 10085288
TI  - The release of cytochrome c from mitochondria during apoptosis of NGF-deprived
      sympathetic neurons is a reversible event.
AB  - During apoptosis induced by various stimuli, cytochrome c is released from
      mitochondria into the cytosol where it participates in caspase activation. This
      process has been proposed to be an irreversible consequence of mitochondrial
      permeability transition pore opening, which leads to mitochondrial swelling and
      rupture of the outer mitochondrial membrane. Here we present data demonstrating
      that NGF-deprived sympathetic neurons protected from apoptosis by caspase
      inhibitors possess mitochondria which, though depleted of cytochrome c and
      reduced in size, remained structurally intact as viewed by electron microscopy.
      After re-exposure of neurons to NGF, mitochondria recovered their normal size and
      their cytochrome c content, by a process requiring de novo protein synthesis.
      Altogether, these data suggest that depletion of cytochrome c from mitochondria
      is a controlled process compatible with function recovery. The ability of
      sympathetic neurons to recover fully from trophic factor deprivation provided
      irreversible caspase inhibitors have been present during the insult period, has
      therapeutical implications for a number of acute neuropathologies.

PMID- 10085289
TI  - Bid-induced conformational change of Bax is responsible for mitochondrial
      cytochrome c release during apoptosis.
AB  - Here we report that in staurosporine-induced apoptosis of HeLa cells, Bid, a BH3
      domain containing protein, translocates from the cytosol to mitochondria. This
      event is associated with a change in conformation of Bax which leads to the
      unmasking of its NH2-terminal domain and is accompanied by the release of
      cytochrome c from mitochondria. A similar finding is reported for cerebellar
      granule cells undergoing apoptosis induced by serum and potassium deprivation.
      The Bax-conformational change is prevented by Bcl-2 and Bcl-xL but not by caspase
      inhibitors. Using isolated mitochondria and various BH3 mutants of Bid, we
      demonstrate that direct binding of Bid to Bax is a prerequisite for Bax
      structural change and cytochrome c release. Bcl-xL can inhibit the effect of Bid
      by interacting directly with Bax. Moreover, using mitochondria from Bax-deficient
      tumor cell lines, we show that Bid- induced release of cytochrome c is negligible
      when Bid is added alone, but dramatically increased when Bid and Bax are added
      together. Taken together, our results suggest that, during certain types of
      apoptosis, Bid translocates to mitochondria and binds to Bax, leading to a change
      in conformation of Bax and to cytochrome c release from mitochondria.

PMID- 10085290
TI  - Cell damage-induced conformational changes of the pro-apoptotic protein Bak in
      vivo precede the onset of apoptosis.
AB  - Investigation of events committing cells to death revealed that a concealed NH2
      terminal epitope of the pro-apoptotic protein Bak became exposed in vivo before
      apoptosis. This occurred after treatment of human Jurkat or CEM-C7A T-lymphoma
      cells with the mechanistically disparate agents staurosporine, etoposide or
      dexamethasone. The rapid, up to 10-fold increase in Bak-associated
      immunofluorescence was measured with epitope-specific monoclonal antibodies using
      flow cytometry and microscopy. In contrast, using a polyclonal antibody to Bak,
      immunofluorescence was detected both before and after treatment. There were no
      differences in Bak protein content nor in subcellular location before or after
      treatment. Immunofluorescence showed Bcl-xL and Bak were largely associated with
      mitochondria and in untreated cells they coimmunoprecipitated in the presence of
      nonioinic detergent. This association was significantly decreased after cell
      perturbation suggesting that Bcl-xL dissociation from Bak occurred on exposure of
      Bak's NH2 terminus. Multiple forms of Bak protein were observed by two
      dimensional electrophoresis but these were unchanged by inducers of apoptosis.
      This indicated that integration of cellular damage signals did not take place
      directly on the Bak protein. Release of proteins, including Bcl-xL, from Bak is
      suggested to be an important event in commitment to death.

PMID- 10085291
TI  - Activation of membrane-associated procaspase-3 is regulated by Bcl-2.
AB  - The mechanism by which membrane-bound Bcl-2 inhibits the activation of
      cytoplasmic procaspases is unknown. Here we characterize an intracellular,
      membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2.
      Heavy membranes isolated from control cells contained a spontaneously activatable
      caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the
      caspase-3 zymogen was still associated with heavy membranes, its spontaneous
      activation was blocked. However, Bcl-2 expression had little effect on the levels
      of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane
      associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to
      activation by exogenous cytochrome c. Our results demonstrate that intracellular
      membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and
      that control of caspase activation in membranes is distinct from that observed in
      the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in
      part by blocking the activation of membrane-associated procaspases.

PMID- 10085292
TI  - Dissection of cell division processes in the one cell stage Caenorhabditis
      elegans embryo by mutational analysis.
AB  - To identify novel components required for cell division processes in complex
      eukaryotes, we have undertaken an extensive mutational analysis in the one cell
      stage Caenorhabditis elegans embryo. The large size and optical properties of
      this cell permit observation of cell division processes with great detail in live
      specimens by simple differential interference contrast (DIC) microscopy. We have
      screened an extensive collection of maternal-effect embryonic lethal mutations on
      chromosome III with time-lapse DIC video microscopy. Using this assay, we have
      identified 48 mutations in 34 loci which are required for specific cell division
      processes in the one cell stage embryo. We show that mutations fall into distinct
      phenotypic classes which correspond, among others, to the processes of pronuclear
      migration, rotation of centrosomes and associated pronuclei, spindle assembly,
      chromosome segregation, anaphase spindle positioning, and cytokinesis. We have
      further analyzed pronuclear migration mutants by indirect immunofluorescence
      microscopy using antibodies against tubulin and ZYG-9, a centrosomal marker. This
      analysis revealed that two pronuclear migration loci are required for generating
      normal microtubule arrays and four for centrosome separation. All 34 loci have
      been mapped by deficiencies to distinct regions of chromosome III, thus paving
      the way for their rapid molecular characterization. Our work contributes to
      establishing the one cell stage C. elegans embryo as a powerful metazoan model
      system for dissecting cell division processes.

PMID- 10085293
TI  - Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p.
AB  - Alignment of the mitotic spindle with the axis of cell division is an essential
      process in Saccharomyces cerevisiae that is mediated by interactions between
      cytoplasmic microtubules and the cell cortex. We found that a cortical protein,
      the yeast formin Bni1p, was required for spindle orientation. Two striking
      abnormalities were observed in bni1Delta cells. First, the initial movement of
      the spindle pole body (SPB) toward the emerging bud was defective. This phenotype
      is similar to that previously observed in cells lacking the kinesin Kip3p and, in
      fact, BNI1 and KIP3 were found to be in the same genetic pathway. Second,
      abnormal pulling interactions between microtubules and the cortex appeared to
      cause preanaphase spindles in bni1Delta cells to transit back and forth between
      the mother and the bud. We therefore propose that Bni1p may localize or alter the
      function of cortical microtubule-binding sites in the bud. Additionally, we
      present evidence that other bipolar bud site determinants together with cortical
      actin are also required for spindle orientation.

PMID- 10085294
TI  - The cortical localization of the microtubule orientation protein, Kar9p, is
      dependent upon actin and proteins required for polarization.
AB  - In the yeast Saccharomyces cerevisiae, positioning of the mitotic spindle
      requires both the cytoplasmic microtubules and actin. Kar9p is a novel cortical
      protein that is required for the correct position of the mitotic spindle and the
      orientation of the cytoplasmic microtubules. Green fluorescent protein (GFP)-
      Kar9p localizes to a single spot at the tip of the growing bud and the mating
      projection. However, the cortical localization of Kar9p does not require
      microtubules (Miller, R.K., and M.D. Rose. 1998. J. Cell Biol. 140: 377),
      suggesting that Kar9p interacts with other proteins at the cortex. To investigate
      Kar9p's cortical interactions, we treated cells with the actin-depolymerizing
      drug, latrunculin-A. In both shmoos and mitotic cells, Kar9p's cortical
      localization was completely dependent on polymerized actin. Kar9p localization
      was also altered by mutations in four genes, spa2Delta, pea2Delta, bud6Delta, and
      bni1Delta, required for normal polarization and actin cytoskeleton functions and,
      of these, bni1Delta affected Kar9p localization most severely. Like kar9Delta,
      bni1Delta mutants exhibited nuclear positioning defects during mitosis and in
      shmoos. Furthermore, like kar9Delta, the bni1Delta mutant exhibited misoriented
      cytoplasmic microtubules in shmoos. Genetic analysis placed BNI1 in the KAR9
      pathway for nuclear migration. However, analysis of kar9Delta bni1Delta double
      mutants suggested that Kar9p retained some function in bni1Delta mitotic cells.
      Unlike the polarization mutants, kar9Delta shmoos had a normal morphology and
      diploids budded in the correct bipolar pattern. Furthermore, Bni1p localized
      normally in kar9Delta. We conclude that Kar9p's function is specific for
      cytoplasmic microtubule orientation and that Kar9p's role in nuclear positioning
      is to coordinate the interactions between the actin and microtubule networks.

PMID- 10085295
TI  - Microtubule dynamics from mating through the first zygotic division in the
      budding yeast Saccharomyces cerevisiae.
AB  - We have used time-lapse digital imaging microscopy to examine cytoplasmic astral
      microtubules (Mts) and spindle dynamics during the mating pathway in budding
      yeast Saccharomyces cerevisiae. Mating begins when two cells of opposite mating
      type come into proximity. The cells arrest in the G1 phase of the cell cycle and
      grow a projection towards one another forming a shmoo projection. Imaging of
      microtubule dynamics with green fluorescent protein (GFP) fusions to dynein or
      tubulin revealed that the nucleus and spindle pole body (SPB) became oriented and
      tethered to the shmoo tip by a Mt-dependent search and capture mechanism.
      Dynamically unstable astral Mts were captured at the shmoo tip forming a bundle
      of three or four astral Mts. This bundle changed length as the tethered nucleus
      and SPB oscillated toward and away from the shmoo tip at growth and shortening
      velocities typical of free plus end astral Mts (approximately 0.5
      micrometer/min). Fluorescent fiduciary marks in Mt bundles showed that Mt growth
      and shortening occurred primarily at the shmoo tip, not the SPB. This indicates
      that Mt plus end assembly/disassembly was coupled to pushing and pulling of the
      nucleus. Upon cell fusion, a fluorescent bar of Mts was formed between the two
      shmoo tip bundles, which slowly shortened (0.23 +/- 0.07 micrometer/min) as the
      two nuclei and their SPBs came together and fused (karyogamy). Bud emergence
      occurred adjacent to the fused SPB approximately 30 min after SPB fusion. During
      the first mitosis, the SPBs separated as the spindle elongated at a constant
      velocity (0.75 micrometer/min) into the zygotic bud. There was no indication of a
      temporal delay at the 2-micrometer stage of spindle morphogenesis or a lag in Mt
      nucleation by replicated SPBs as occurs in vegetative mitosis implying a lack of
      normal checkpoints. Thus, the shmoo tip appears to be a new model system for
      studying Mt plus end dynamic attachments and much like higher eukaryotes, the
      first mitosis after haploid cell fusion in budding yeast may forgo cell cycle
      checkpoints present in vegetative mitosis.

PMID- 10085296
TI  - Specific myosin heavy chain mutations suppress troponin I defects in Drosophila
      muscles.
AB  - We show that specific mutations in the head of the thick filament molecule myosin
      heavy chain prevent a degenerative muscle syndrome resulting from the hdp2
      mutation in the thin filament protein troponin I. One mutation deletes eight
      residues from the actin binding loop of myosin, while a second affects a residue
      at the base of this loop. Two other mutations affect amino acids near the site of
      nucleotide entry and exit in the motor domain. We document the degree of
      phenotypic rescue each suppressor permits and show that other point mutations in
      myosin, as well as null mutations, fail to suppress the hdp2 phenotype. We
      discuss mechanisms by which the hdp2 phenotypes are suppressed and conclude that
      the specific residues we identified in myosin are important in regulating thick
      and thin filament interactions. This in vivo approach to dissecting the
      contractile cycle defines novel molecular processes that may be difficult to
      uncover by biochemical and structural analysis. Our study illustrates how
      expression of genetic defects are dependent upon genetic background, and
      therefore could have implications for understanding gene interactions in human
      disease.

PMID- 10085297
TI  - Ponsin/SH3P12: an l-afadin- and vinculin-binding protein localized at cell-cell
      and cell-matrix adherens junctions.
AB  - We recently isolated a novel actin filament (F-actin)-binding protein, afadin,
      that has two isoforms, l- and s-afadins. l-Afadin is ubiquitously expressed and
      specifically localized at zonula adherens (ZA) in epithelial cells and at cell
      cell adherens junction (AJ) in nonepithelial cells, whereas s-afadin is
      abundantly expressed in neural tissue. l-Afadin has one PDZ domain, three proline
      rich regions, and one F-actin-binding domain, whereas s-afadin lacks the third
      proline-rich region and the F-actin-binding domain. To understand the molecular
      mechanism of the specific localization of l-afadin at ZA in epithelial cells and
      at cell-cell AJ in nonepithelial cells, we attempted here to identify an l-afadin
      binding protein(s) and isolated a protein, named ponsin. Ponsin had many splicing
      variants and the primary structures of two of them were determined. Both the two
      variants had three Src homology 3 (SH3) domains and turned out to be splicing
      variants of SH3P12. The third proline-rich region of l-afadin bound to the region
      of ponsin containing the second and third SH3 domains. Ponsin was ubiquitously
      expressed and localized at ZA in epithelial cells, at cell-cell AJ in
      nonepithelial cells, and at cell-matrix AJ in both types of cells. Ponsin
      furthermore directly bound vinculin, an F-actin-binding protein localized at ZA
      in epithelial cells, at cell-cell AJ in nonepithelial cells, and at cell-matrix
      AJ in both types of cells. Vinculin has one proline-rich region where two proline
      rich sequences are located. The proline-rich region bound to the region of ponsin
      containing the first and second SH3 domains. l-Afadin and vinculin bound to
      ponsin in a competitive manner and these three proteins hardly formed a ternary
      complex. These results indicate that ponsin is an l-afadin- and vinculin-binding
      protein localized at ZA in epithelial cells, at cell-cell AJ in nonepithelial
      cells, and at cell-matrix AJ in both types of cells.

PMID- 10085298
TI  - Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly,
      migration, and cytokinesis in fibroblasts.
AB  - In this article, we show that, in transfected COS-1 cells, protein tyrosine
      phosphatase (PTP)-PEST translocates to the membrane periphery following
      stimulation by the extracellular matrix protein fibronectin. When plated on
      fibronectin, PTP-PEST (-/-) fibroblasts display a strong defect in motility. 3 h
      after plating on fibronectin, the number and size of vinculin containing focal
      adhesions were greatly increased in the homozygous PTP-PEST mutant cells as
      compared with heterozygous cells. This phenomenon appears to be due in part to a
      constitutive increase in tyrosine phosphorylation of p130(CAS), a known PTP-PEST
      substrate, paxillin, which associates with PTP-PEST in vitro, and focal adhesion
      kinase (FAK). Another effect of this constitutive hyperphosphorylation,
      consistent with the focal adhesion regulation defect, is that (-/-) cells spread
      faster than the control cell line when plated on fibronectin. In the PTP-PEST (-/
      ) cells, an increase in affinity for the SH2 domains of Src and Crk towards
      p130(CAS) was also observed. In (-/-) cells, we found a significant increase in
      the level of tyrosine phosphorylation of PSTPIP, a cleavage furrow-associated
      protein that interacts physically with all PEST family members. An effect of
      PSTPIP hyperphosphorylation appears to be that some cells remain attached at the
      site of the cleavage furrow for an extended period of time. In conclusion, our
      data suggest PTP-PEST plays a dual role in cell cytoskeleton organization, by
      promoting the turnover of focal adhesions required for cell migration, and by
      directly or indirectly regulating the proline, serine, threonine phosphatase
      interacting protein (PSTPIP) tyrosine phosphorylation level which may be involved
      in regulating cleavage furrow formation or disassembly during normal cell
      division.

PMID- 10085299
TI  - Dissection of the molecular basis of pp60(v-src) induced gating of connexin 43
      gap junction channels.
AB  - Suppression of gap-junctional communication by various protein kinases, growth
      factors, and oncogenes frequently correlates with enhanced mitogenesis. The
      oncogene v-src appears to cause acute closure of gap junction channels. Tyr265 in
      the COOH-terminal tail of connexin 43 (Cx43) has been implicated as a potential
      target of v-src, although v-src action has also been associated with changes in
      serine phosphorylation. We have investigated the mechanism of this acute
      regulation through mutagenesis of Cx43 expressed in Xenopus laevis oocyte pairs.
      Truncations of the COOH-terminal domain led to an almost complete loss of
      response of Cx43 to v-src, but this was restored by coexpression of the
      independent COOH-terminal polypeptide. This suggests a ball and chain gating
      mechanism, similar to the mechanism proposed for pH gating of Cx43, and K+
      channel inactivation. Surprisingly, we found that v-src mediated gating of Cx43
      did not require the tyrosine site, but did seem to depend on the presence of two
      potential SH3 binding domains and the mitogen-activated protein (MAP) kinase
      phosphorylation sites within them. Further point mutagenesis and pharmacological
      studies in normal rat kidney (NRK) cells implicated MAP kinase in the gating
      response to v-src, while the stable binding of v-src to Cx43 (in part mediated by
      SH3 domains) did not correlate with its ability to mediate channel closure. This
      suggests a common link between closure of gap junctions by v-src and other
      mitogens, such as EGF and lysophosphatidic acid (LPA).

PMID- 10085300
TI  - Differential regulation of beta1 integrins by chemoattractants regulates
      neutrophil migration through fibrin.
AB  - Chemoattractants differ in their capacity to stimulate neutrophils to adhere to
      and to migrate through matrices containing fibrin. Formyl methionyl leucyl
      phenylalanine (fMLP) stimulates neutrophils to adhere closely to, but not to
      migrate into, fibrin gels. Leukotriene B4 (LTB4) stimulates neutrophils to adhere
      loosely to and to migrate through fibrin gels. We report that alpha5beta1
      integrins regulate the different migratory behaviors on fibrin gels of
      neutrophils in response to these chemoattractants. fMLP, but not LTB4, activated
      neutrophil beta1 integrins, as measured by binding of mAb 15/7 to an activation
      epitope on the beta1 integrins. Antibodies or peptides that block alpha5beta1
      integrins prevented fMLP-stimulated neutrophils from forming zones of close
      apposition on fibrin and reversed fMLP's inhibitory effect on neutrophil
      chemotaxis through fibrin. In contrast, neither peptides nor antibodies that
      block beta1 integrins affected the capacity of LTB4-stimulated neutrophils to
      form zones of loose apposition or to migrate through fibrin gels. These results
      suggest that chemoattractants generate at least two different messages that
      direct neutrophils, and perhaps other leukocytes, to accumulate at specific
      anatomic sites: a general message that induces neutrophils to crawl and a
      specific message that prepares neutrophils to stop when they contact appropriate
      matrix proteins for activated beta1 integrins.

PMID- 10085301
TI  - Hensin remodels the apical cytoskeleton and induces columnarization of
      intercalated epithelial cells: processes that resemble terminal differentiation.
AB  - Intercalated epithelial cells exist in a spectrum of phenotypes; at one extreme,
      beta cells secrete HCO3 by an apical Cl/HCO3 exchanger and a basolateral H+
      ATPase. When an immortalized beta cell line is seeded at high density it deposits
      in its extracellular matrix (ECM) a new protein, hensin, which can reverse the
      polarity of several proteins including the Cl/HCO3 exchanger (an alternately
      spliced form of band 3) and the proton translocating ATPase. When seeded at low
      density and allowed to form monolayers these polarized epithelial cells maintain
      the original distribution of these two proteins. Although these cells synthesize
      and secrete hensin, it is not retained in the ECM, but rather, hensin is present
      in a large number of intracellular vesicles. The apical cytoplasm of low density
      cells is devoid of actin, villin, and cytokeratin19. Scanning electron microscopy
      shows that these cells have sparse microvilli, whereas high density cells have
      exuberant apical surface infolding and microvilli. The apical cytoplasm of high
      density cells contains high levels of actin, cytokeratin19, and villin. The cell
      shape of these two phenotypes is different with high density cells being tall
      with a small cross-sectional area, whereas low density cells are low and flat.
      This columnarization and the remodeling of the apical cytoplasm is hensin
      dependent; it can be induced by seeding low density cells on filters conditioned
      by high density cells and prevented by an antibody to hensin. The changes in cell
      shape and apical cytoskeleton are reminiscent of the processes that occur in
      terminal differentiation of the intestine and other epithelia. Hensin is highly
      expressed in the intestine and prostate (two organs where there is a continuous
      process of differentiation). The expression of hensin in the less differentiated
      crypt cells of the intestine and the basal cells of the prostate is similar to
      that of low density cells; i.e., abundant intracellular vesicles but no
      localization in the ECM. On the other hand, as in high density cells hensin is
      located exclusively in the ECM of the terminally differentiated absorptive villus
      cells and the prostatic luminal cell. These studies suggest that hensin is a
      critical new molecule in the terminal differentiation of intercalated cell and
      perhaps other epithelial cells.

PMID- 10085302
TI  - Type IIA procollagen containing the cysteine-rich amino propeptide is deposited
      in the extracellular matrix of prechondrogenic tissue and binds to TGF-beta1 and
      BMP-2.
AB  - Type II procollagen is expressed as two splice forms. One form, type IIB, is
      synthesized by chondrocytes and is the major extracellular matrix component of
      cartilage. The other form, type IIA, contains an additional 69 amino acid
      cysteine-rich domain in the NH2-propeptide and is synthesized by chondrogenic
      mesenchyme and perichondrium. We have hypothesized that the additional protein
      domain of type IIA procollagen plays a role in chondrogenesis. The present study
      was designed to determine the localization of the type IIA NH2-propeptide and its
      function during chondrogenesis. Immunofluorescence histochemistry using
      antibodies to three domains of the type IIA procollagen molecule was used to
      localize the NH2-propeptide, fibrillar domain, and COOH-propeptides of the type
      IIA procollagen molecule during chondrogenesis in a developing human long bone
      (stage XXI). Before chondrogenesis, type IIA procollagen was synthesized by
      chondroprogenitor cells and deposited in the extracellular matrix. Immunoelectron
      microscopy revealed type IIA procollagen fibrils labeled with antibodies to NH2
      propeptide at approximately 70 nm interval suggesting that the NH2-propeptide
      remains attached to the collagen molecule in the extracellular matrix. As
      differentiation proceeds, the cells switch synthesis from type IIA to IIB
      procollagen, and the newly synthesized type IIB collagen displaces the type IIA
      procollagen into the interterritorial matrix. To initiate studies on the function
      of type IIA procollagen, binding was tested between recombinant NH2-propeptide
      and various growth factors known to be involved in chondrogenesis. A solid phase
      binding assay showed no reaction with bFGF or IGF-1, however, binding was
      observed with TGF-beta1 and BMP-2, both known to induce endochondral bone
      formation. BMP-2, but not IGF-1, coimmunoprecipitated with type IIA NH2
      propeptide. Recombinant type IIA NH2-propeptide and type IIA procollagen from
      media coimmunoprecipitated with BMP-2 while recombinant type IIB NH2-propeptide
      and all other forms of type II procollagens and mature collagen did not react
      with BMP-2. Taken together, these results suggest that the NH2-propeptide of type
      IIA procollagen could function in the extracellular matrix distribution of bone
      morphogenetic proteins in chondrogenic tissue.

PMID- 10085324
TI  - NOS inhibitor antagonism of PGE2-induced mechanical sensitization of cutaneous C
      fiber nociceptors in the rat.
AB  - Prostaglandins, metabolites of arachidonic acid, released during tissue injury
      and inflammation sensitize primary afferent nociceptors. While it has been
      suggested that this effect on nociceptors is mediated mainly via the cAMP second
      messenger system, recent evidence suggests that nitric oxide (NO) is also
      involved in peripheral pain mechanisms. To test the hypothesis that NO
      contributes to the sensitization of nociceptors to mechanical stimuli induced by
      hyperalgesic prostaglandins, we compared von Frey hair mechanical threshold as
      well as the response evoked by 10-s sustained threshold mechanical stimulation
      before and after injection of prostaglandin E2 (PGE2) alone, and NOS inhibitor NG
      methyl-L-arginine (L-NMA) or its inactive stereoisomer NG-methyl-D-arginine (D
      NMA) plus PGE2, adjacent to the receptive field of C-fiber nociceptors. The
      reduction of mechanical threshold and increase in number of action potentials to
      sustained mechanical stimulation induced by intradermal application of PGE2 was
      blocked by L-NMA, but not D-NMA. It is suggested that NO contributes to
      nociceptor sensitization induced by hyperalgesic prostaglandins.

PMID- 10085325
TI  - Dopamine modulation of membrane and synaptic properties of interneurons in rat
      cerebral cortex.
AB  - Dopamine (DA) is an endogenous neuromodulator in the mammalian brain. However, it
      is still controversial how DA modulates excitability and input-output relations
      in cortical neurons. It was suggested that DA innervation of dendritic spines
      regulates glutamatergic inputs to pyramidal neurons, but no experiments were done
      to test this idea. By recording individual neurons under direct visualization we
      found that DA enhances inhibitory neuron excitability but decreases pyramidal
      cell excitability, through depolarization and hyperpolarization, respectively.
      Accordingly, DA also increased the frequency and amplitude of spontaneous
      inhibitory postsynaptic currents (sIPSCs). In the presence of TTX, DA did not
      affect the frequency, amplitude, or kinetics of miniature IPSCs and excitatory
      postsynaptic currents in inhibitory interneurons or pyramidal cells. Our results
      suggest that DA can directly excite cortical interneurons, but there is no
      detectable DA gate to regulate spontaneous GABA and glutamate release or the
      properties of postsynaptic GABA and glutamate receptors in neocortical neurons.

PMID- 10085326
TI  - Blockade of SK-type Ca2+-activated K+ channels uncovers a Ca2+-dependent slow
      afterdepolarization in nigral dopamine neurons.
AB  - Sharp electrode current-clamp recording techniques were used to characterize the
      response of nigral dopamine (DA)-containing neurons in rat brain slices to
      injected current pulses applied in the presence of TTX (2 microM) and under
      conditions in which apamin-sensitive Ca2+-activated K+ channels were blocked.
      Addition of apamin (100-300 nM) to perfusion solutions containing TTX blocked the
      pacemaker oscillation in membrane voltage evoked by depolarizing current pulses
      and revealed an afterdepolarization (ADP) that appeared as a shoulder on the
      falling phase of the voltage response. ADP were preceded by a ramp-shaped slow
      depolarization and followed by an apamin-insensitive hyperpolarizing
      afterpotential (HAP). Although ADPs were observed in all apamin-treated cells,
      the duration of the response varied considerably between individual neurons and
      was strongly potentiated by the addition of TEA (2-3 mM). In the presence of TTX,
      TEA, and apamin, optimal stimulus parameters (0.1 nA, 200-ms duration at -55 to 
      68 mV) evoked ADP ranging from 80 to 1,020 ms in duration (355.3 +/- 56.5 ms, n =
      16). Both the ramp-shaped slow depolarization and the ensuing ADP were markedly
      voltage dependent but appeared to be mediated by separate conductance mechanisms.
      Thus, although bath application of nifedipine (10-30 microM) or low Ca2+, high
      Mg2+ Ringer blocked the ADP without affecting the ramp potential, equimolar
      substitution of Co2+ for Ca2+ blocked both components of the voltage response.
      Nominal Ca2+ Ringer containing Co2+ also blocked the HAP evoked between -55 and 
      68 mV. We conclude that the ADP elicited in DA neurons after blockade of apamin
      sensitive Ca2+-activated K+ channels is mediated by a voltage-dependent, L-type
      Ca2+ channel and represents a transient form of the regenerative plateau
      oscillation in membrane potential previously shown to underlie apamin-induced
      bursting activity. These data provide further support for the notion that
      modulation of apamin-sensitive Ca2+-activated K+ channels in DA neurons exerts a
      permissive effect on the conductances that are involved in the expression of
      phasic activity.

PMID- 10085327
TI  - Voltage-gated Ca2+ conductances in acutely isolated guinea pig dorsal cochlear
      nucleus neurons.
AB  - Although it is known that voltage-gated Ca2+ conductances (VGCCs) contribute to
      the responses of dorsal cochlear nucleus (DCN) neurons, little is known about the
      properties of VGCCs in the DCN. In this study, the whole cell voltage-clamp
      technique was used to examine the pharmacology and voltage dependence of VGCCs in
      unidentified DCN neurons acutely isolated from guinea pig brain stem. The
      majority of cells responded to depolarization with sustained inward currents that
      were enhanced when Ca2+ was replaced by Ba2+, were blocked partially by Ni2+ (100
      microM), and were blocked almost completely by Cd2+ (50 microM). Experiments
      using nifedipine (10 microM), omegaAga IVA (100 nM) and omegaCTX GVIA (500 nM)
      demonstrated that a variety of VGCC subtypes contributed to the Ba2+ current in
      most cells, including the L, N, and P/Q types and antagonist-insensitive R type.
      Although a large depolarization from rest was required to activate VGCCs in DCN
      neurons, VGCC activation was rapid at depolarized levels, having time constants
      <1 ms at 22 degrees C. No fast low-threshold inactivation was observed, and a
      slow high-threshold inactivation was observed at voltages more positive than -20
      mV, indicating that Ba2+ currents were carried by high-voltage activated VGCCs.
      The VGCC subtypes contributing to the overall Ba2+ current had similar voltage
      dependent properties, with the exception of the antagonist-insensitive R-type
      component, which had a slower activation and a more pronounced inactivation than
      the other components. These data suggest that a variety of VGCCs is present in
      DCN neurons, and these conductances generate a rapid Ca2+ influx in response to
      depolarizing stimuli.

PMID- 10085328
TI  - Synchronization of local neural networks in the somatosensory cortex: A
      comparison of stationary and moving stimuli.
AB  - Spontaneous and stimulus-induced responses were recorded from neighboring groups
      of neurons by an array of electrodes in the primary (SI) somatosensory cortex of
      intact, halothane-anesthetized cats. Cross-correlation analysis was used to
      characterize the coordination of spontaneous activity and the responses to
      peripheral stimulation with moving or stationary air jets. Although
      synchronization was detected in only 10% (88 of 880) of the pairs of single
      neurons that were recorded, cross-correlation analysis of multiunit responses
      revealed significant levels of synchronization in 64% of the 123 recorded
      electrode pairs. Compared with spontaneous activity, both stationary and moving
      air jets caused substantial increases in the rate, proportion, and temporal
      precision of synchronized activity in local regions of SI cortex. Among
      populations of neurons that were synchronized by both types of air-jet
      stimulation, the mean rate of synchronized activity was significantly higher
      during moving air-jet stimulation than during stationary air-jet stimulation.
      Moving air jets also produced significantly higher correlation coefficients than
      stationary air jets in the raw cross-correlograms (CCGs) but not in the shift
      corrected CCGs. The incidence and rate of stimulus-induced synchronization varied
      with the distance separating the recording sites. For sites separated by </=300
      microm, 80% of the multiunit responses displayed significant levels of
      synchronization during both types of air-jet stimulation. For sites separated by
      >/=500 microm, only 37% of the multiunit responses were synchronized by discrete
      stimulation with a single air jet. Measurements of the multiunit CCG peak half
      widths showed that the correlated activity produced by moving air jets had
      slightly less temporal variability than that produced by stationary air jets.
      These results indicate that moving stimuli produce greater levels of
      synchronization than stationary stimuli among local groups of SI neurons and
      suggest that neuronal synchronization may supplement the changes in firing rate
      which code intensity and other attributes of a cutaneous stimulus.

PMID- 10085329
TI  - Role of GABAB receptor-mediated inhibition in reciprocal interareal pathways of
      rat visual cortex.
AB  - In neocortex, synaptic inhibition is mediated by gamma-aminobutyric acid-A
      (GABAA) and GABAB receptors. By using intracellular and patch-clamp recordings in
      slices of rat visual cortex we studied the balance of excitation and inhibition
      in different intracortical pathways. The study was focused on the strength of
      fast GABAA- and slow GABAB-mediated inhibition in interareal forward and feedback
      connections between area 17 and the secondary, latero-medial visual area (LM).
      Our results demonstrate that in most layer 2/3 neurons forward inputs elicited
      excitatory postsynaptic potentials (EPSPs) that were followed by fast GABAA- and
      slow GABAB-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPs).
      These responses resembled those elicited by horizontal connections within area 17
      and those evoked by stimulation of the layer 6/white matter border. In contrast,
      in the feedback pathway hyperpolarizing fast and slow IPSPs were rare. However
      weak fast and slow IPSPs were unmasked by bath application of GABAB receptor
      antagonists. Because in the feedback pathway disynaptic fast and slow IPSPs were
      rare, polysynaptic EPSPs were more frequent than in forward, horizontal, and
      interlaminar circuits and were activated over a broader stimulus range. In
      addition, in the feedback pathway large-amplitude polysynaptic EPSPs were longer
      lasting and showed a late component whose onset coincided with that of slow
      IPSPs. In the forward pathway these late EPSPs were only seen with stimulus
      intensities that were below the activation threshold of slow IPSPs. Unlike strong
      forward inputs, feedback stimuli of a wide range of intensities increased the
      rate of ongoing neuronal firing. Thus, when forward and feedback inputs are
      simultaneously active, feedback inputs may provide late polysynaptic excitation
      that can offset slow IPSPs evoked by forward inputs and in turn may promote
      recurrent excitation through local intracolumnar circuits. This may provide a
      mechanism by which feedback inputs from higher cortical areas can amplify
      afferent signals in lower areas.

PMID- 10085330
TI  - Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in
      domestic chickens.
AB  - Avian auditory and vestibular hair cells regenerate after damage by ototoxic
      drugs, but until recently there was little evidence that regenerated vestibular
      hair cells function normally. In an earlier study we showed that the
      vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic
      treatment and recovers as hair cells regenerate. The VOR, which stabilizes the
      eye in the head, is an open-loop system that is thought to depend largely on
      regularly firing afferents. Recovery of the VOR is highly correlated with the
      regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR),
      which stabilizes the head in space, is a closed-loop, negative-feedback system
      that seems to depend more on irregularly firing afferent input and is thought to
      be subserved by different circuitry than the VOR. We examined whether this
      different reflex also of vestibular origin would show similar recovery after hair
      cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were
      created by a 5-day course of streptomycin sulfate. One day after completion of
      streptomycin treatment there was no measurable VCR gain, and total hair cell
      density was approximately 35% of that in untreated, age-matched controls. At 2 wk
      postlesion there was significant recovery of the VCR; at this time two subjects
      showed VCR gains within the range of control chicks. At 3 wk postlesion all
      subjects showed VCR gains and phase shifts within the normal range. These data
      show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain
      correlates equally well with the density of regenerating type I and type II
      vestibular hair cells, except at high frequencies. Several factors other than
      hair cell regeneration, such as length of stereocilia, reafferentation of hair
      cells, and compensation involving central neural pathways, may be involved in
      behavioral recovery. Our data suggest that one or more of these factors
      differentially affect the recovery of these two vestibular reflexes.

PMID- 10085331
TI  - Long-term depression of temporoammonic-CA1 hippocampal synaptic transmission.
AB  - The temporoammonic pathway, the direct projection from layer III of the
      entorhinal cortex to area CA1 of the hippocampus, includes both excitatory and
      inhibitory components that are positioned to be an important source of modulation
      of the hippocampal output. However, little is known about synaptic plasticity in
      this pathway. We used field recordings in hippocampal slices prepared from mature
      (6- to 8-wk old) rats to study long-term depression (LTD) in the temporoammonic
      pathway. Low-frequency (1 Hz) stimulation (LFS) for 10 min resulted in a
      depression of the field response that lasted for >/=1 h. This depression was
      saturable by multiple applications of LFS. LTD induction was unaffected by the
      blockade of either fast (GABAA) or slow (GABAB) inhibition. Temporoammonic LTD
      was inhibited by the presence of the N-methyl-D-aspartate (NMDA) receptor
      antagonist AP5, suggesting a dependence on calcium influx. Full recovery from
      depression could be induced by high-frequency (100 Hz) stimulation (HFS); in the
      presence of the GABAA antagonist bicuculline, HFS induced recovery above the
      original baseline level. Similarly, HFS or theta-burst stimulation (TBS) applied
      to naive slices caused little potentiation, whereas HFS or TBS applied in the
      presence of bicuculline resulted in significant potentiation of the
      temporoammonic response. Our results show that, unlike the Schaffer collateral
      input to CA1, the temporoammonic input in mature animals is easy to depress but
      difficult to potentiate.

PMID- 10085332
TI  - Intersegmental dynamics are controlled by sequential anticipatory, error
      correction, and postural mechanisms.
AB  - The purpose of this study is to examine the mechanisms underlying control of
      intersegmental dynamics during reaching movements. Two experiments were conducted
      to determine the relative contributions of anticipatory and somatosensory
      feedback mechanisms in controlling intersegmental dynamics and whether adaptation
      to novel intersegmental dynamics generalizes across a range of movement
      directions. The mechanisms used to control interaction torques were examined by
      altering the inertial load of the forearm. Movements were restricted to the
      shoulder and elbow and supported on a horizontal plane by a frictionless air-jet
      system. Subjects made rapid out-and-back movements over a target line presented
      on a computer screen. The screen cursor disappeared at movement onset, and hand
      paths were displayed after each movement. After subjects adapted to a novel
      inertial configuration, the position of an attached mass was changed on
      pseudorandom trials. During these "surprise" trials, movements were initiated
      with the torque patterns appropriate to the previously learned inertial
      condition. As a result, characteristic errors in initial movement direction were
      predicted by an open-looped forward simulation. After these errors occurred,
      feedback mediated changes in torque emerged that, surprisingly, further decreased
      the accuracy of movement reversals. Nevertheless at the end of movement, the hand
      consistently returned to the starting position. It is plausible that the final
      position was determined completely by feedback-mediated changes in torque. In a
      second experiment, adaptation to a novel inertial load during movements made in a
      single direction showed limited transfer across a range of directions. These
      findings support and extend those of previous reports, which indicated combined
      anticipatory and postural mechanisms to coordinate rapid reaching movements. The
      current results indicate a three-stage control system that sequentially links
      anticipatory, error correction, and postural mechanisms to control intersegmental
      dynamics. Our results, showing limited generalization across directions, are
      consistent with previous reports examining adaptation to externally applied
      forces and extend those findings to indicate that the nervous system uses sensory
      information to recalibrate internal representations of the musculoskeletal
      apparatus itself.

PMID- 10085333
TI  - Cross-correlation study of the temporal interactions between areas V1 and V2 of
      the macaque monkey.
AB  - Cross-correlation studies performed in cat visual cortex have shown that neurons
      in different cortical areas of the same hemisphere or in corresponding areas of
      opposite hemispheres tend to synchronize their activities. The presence of
      synchronization may be related to the parallel organization of the cat visual
      system, in which different cortical areas can be activated in parallel from the
      lateral geniculate nucleus. We wanted to determine whether interareal
      synchronization of firing can also be observed in the monkey, in which cortical
      areas are thought to be organized in a hierarchy spanning different levels. Cross
      correlation histograms (CCHs) were calculated from pairs of single or pairs of
      multiunit activities simultaneously recorded in areas V1 and V2 of paralyzed and
      anesthetized macaque monkeys. Moving bars and flashed bars were used as stimuli.
      The shift predictor was calculated and subtracted from the raw CCH to reveal
      interactions of neuronal origin in isolation. Significant CCH peaks, indicating
      interactions of neuronal origin, were obtained in 11% of the dual single-unit
      recordings and 46% of the dual multiunit recordings with moving bars. The
      incidence of nonflat CCHs with flashed bars was 29 and 78%, respectively. For the
      pairs of recording sites where both flashed and moving stimuli were used, the
      incidences of significant CCHs were very similar. Three types of peaks were
      distinguished on the basis of their width at half-height: T (<16 ms), C (between
      16 and 180 ms), and H peaks (>180 ms). T peaks were very rarely observed (<1% in
      single-unit recordings). H peaks were observed in 7-16% of the single-unit CCHs,
      and C peaks in 6-16%, depending on the stimulus used. C and H peaks were observed
      more often when the receptive fields were overlapping or distant by <2 degrees.
      To test for the presence of synchronization between neurons in areas V1 and V2,
      we measured the position of the CCH peak with respect to the origin of the time
      axis of the CCH. Only in the case of a few T peaks did we find displaced peaks,
      indicating a possible drive of the V2 neuron by the simultaneously recorded V1
      cell. All the other peaks were either centered on the origin or overlapped the
      origin of time with their upper halves. Thus similarly to what has been reported
      for the cat, neurons belonging to different cortical areas in the monkey tend to
      synchronize the time of emission of their action potentials with three different
      levels of temporal precision. For peaks calculated from flashed stimuli, we
      compared the peak position with the difference between latencies of V1 and V2
      neurons. There was a clear correlation for single-unit pairs in the case of C
      peaks. Thus the position of a C peak on the time axis appears to reflect the
      order of visual activation of the correlated neurons. The coupling strength for H
      peaks was smaller during visual drive compared with spontaneous activity. On the
      contrary, C peaks were seen more often and were stronger during visual
      stimulation than during spontaneous activity. This suggests that C-type
      synchronization is associated with the processing of visual information. The
      origin of synchronized activity in a serially organized system is discussed.

PMID- 10085334
TI  - Nitric oxide mediates the central sensitization of primate spinothalamic tract
      neurons.
AB  - Nitric oxide (NO) has been proposed to contribute to the development of
      hyperalgesia by activating the NO/guanosine 3',5'-cyclic monophosphate (cGMP)
      signal transduction pathway in the spinal cord. We have examined the effects of
      NO on the responses of primate spinothalamic tract (STT) neurons to peripheral
      cutaneous stimuli and on the sensitization of STT cells following intradermal
      injection of capsaicin. The NO level within the spinal dorsal horn was increased
      by microdialysis of a NO donor, 3-morpholinosydnonimine (SIN-1). SIN-1 enhanced
      the responses of STT cells to both weak and strong mechanical stimulation of the
      skin. This effect was preferentially on deep wide dynamic range STT neurons. The
      responses of none of the neurons tested to noxious heat stimuli were
      significantly changed when SIN-1 was administered. Intradermal injection of
      capsaicin increased dramatically the content of NO metabolites, NO-2/NO-3, within
      the dorsal horn. This effect was attenuated by pretreatment of the spinal cord
      with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME). Sensitization of STT cells induced by intradermal injection of capsaicin
      was also prevented by pretreatment of the dorsal horn with the NOS inhibitors, L
      NAME or 7-nitroindazole. Blockade of NOS did not significantly affect the
      responses of STT cells to peripheral stimulation in the absence of capsaicin
      injection. The data suggest that NO contributes to the development and
      maintenance of central sensitization of STT cells and the resultant mechanical
      hyperalgesia and allodynia after peripheral tissue damage or inflammation. NO
      seems to play little role in signaling peripheral stimuli under physiological
      conditions.

PMID- 10085335
TI  - Nitric oxide-mediated spinal disinhibition contributes to the sensitization of
      primate spinothalamic tract neurons.
AB  - This study concentrated on whether an increase in spinal nitric oxide (NO)
      diminishes inhibition of spinothalamic tract (STT) cells induced by activating
      the periaqueductal gray (PAG) or spinal glycinergic and GABAergic receptors, thus
      contributing to the sensitization of STT neurons. A reduction in inhibition of
      the responses to cutaneous mechanical stimuli induced by PAG stimulation was seen
      in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal
      horn when these neurons were sensitized during administration of a NO donor, 3
      morpholinosydnonimine (SIN-1), into the dorsal horn by microdialysis. In
      contrast, PAG-induced inhibition of the responses of high-threshold (HT) and
      superficial WDR STT cells was not significantly changed by spinal infusion of SIN
      1. A reduction in PAG inhibition when STT cells were sensitized after intradermal
      injection of capsaicin could be nearly completely blocked by pretreatment of the
      dorsal horn with a NO synthase inhibitor, 7-nitroindazole. Moreover, spinal
      inhibition of nociceptive activity of deep WDR STT neurons elicited by
      iontophoretic release of glycine and GABA agonists was attenuated by
      administration of SIN-1. This change paralleled the change in PAG-induced
      inhibition. However, the inhibition of HT and superficial WDR cells induced by
      glycine and GABA release did not show a significant change when SIN-1 was
      administered spinally. Combined with our recent results, these data show that the
      effectiveness of spinal inhibition can be reduced by the NO/cGMP pathway. Thus
      disinhibition may constitute one mechanism underlying central sensitization.

PMID- 10085336
TI  - Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is
      modulated by guanosine 3',5'-cyclic monophosphate.
AB  - Our recent work has suggested that the nitric oxide/guanosine 3', 5'-cyclic
      monophosphate (NO/cGMP) signal transduction system contributes to central
      sensitization of spinothalamic tract (STT) neurons in part by influencing the
      descending inhibition of nociception resulting from stimulation in the
      periaqueductal gray. This study was designed to examine further whether
      activation of the NO/cGMP cascade reduces the inhibition of the activity of STT
      neurons mediated by spinal inhibitory amino acid (IAA) receptors. Responses of
      STT cells to noxious cutaneous stimuli were inhibited by iontophoresis of glycine
      and GABA agonists in anesthetized monkeys. Administration of 8-bromoguanosine
      3',5'-cyclophosphate sodium (8-bromo-cGMP), a membrane permeable analogue of
      cGMP, either by microdialysis or by iontophoresis reduced significantly the IAA
      induced inhibition of wide dynamic range (WDR) STT cells in the deep layers of
      the dorsal horn. The reduction in inhibition lasted for up to 1-1.5 h after the
      cessation of drug infusion. In contrast, IAA-induced inhibition of WDR STT cells
      in the superficial dorsal horn and high-threshold (HT) cells in superficial or
      deep layers was not significantly changed during 8-bromo-cGMP infusion.
      Iontophoresis of 8-bromo-cGMP onto STT cells produced the same actions as
      produced by microdialysis of this agent, but the effect was not as long-lasting
      nor as potent. Finally, an attenuation of the IAA receptor-mediated inhibition of
      STT cells produced by iontophoretic release of a NO donor, 3
      morpholinosydnonimine, could be blocked by pretreatment of the spinal cord with a
      guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. These
      results suggest that an increased spinal cGMP level contributes to the
      sensitization of WDR STT neurons in the deep dorsal horn in part by down
      regulating spinal IAA receptors. However, no evidence is provided in this study
      that the NO/cGMP cascade regulates IAA receptors on HT and superficial WDR
      neurons. Combined with the preceding studies, our data support the view that NO
      and cGMP function in the same signal transduction cascade and play an important
      role in central sensitization.

PMID- 10085337
TI  - Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia
      and in vitro sensitization of rat nociceptors.
AB  - Hyperalgesic and nociceptor sensitizing effects mediated by the beta-adrenergic
      receptor were evaluated in the rat. Intradermal injection of epinephrine, the
      major endogenous ligand for the beta-adrenergic receptor, into the dorsum of the
      hindpaw of the rat produced a dose-dependent mechanical hyperalgesia, quantified
      by the Randall-Selitto paw-withdrawal test. Epinephrine-induced hyperalgesia was
      attenuated significantly by intradermal pretreatment with propranolol, a beta
      adrenergic receptor antagonist, but not by phentolamine, an alpha-adrenergic
      receptor antagonist. Epinephrine-induced hyperalgesia developed rapidly; it was
      statistically significant by 2 min after injection, reached a maximum effect
      within 5 min, and lasted 2 h. Injection of a more beta-adrenergic receptor
      selective agonist, isoproterenol, also produced dose-dependent hyperalgesia,
      which was attenuated by propranolol but not phentolamine. Epinephrine-induced
      hyperalgesia was not affected by indomethacin, an inhibitor of cyclo-oxygenase,
      or by surgical sympathectomy. It was attenuated significantly by inhibitors of
      the adenosine 3',5'-cyclic monophosphate signaling pathway (the adenylyl cyclase
      inhibitor, SQ 22536, and the protein kinase A inhibitors, Rp-adenosine 3',5'
      cyclic monophosphate and WIPTIDE), inhibitors of the protein kinase C signaling
      pathway (chelerythrine and bisindolylmaleimide) and a mu-opioid receptor agonist
      DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Consistent with the hypothesis
      that epinephrine produces hyperalgesia by a direct action on primary afferent
      nociceptors, it was found to sensitize small-diameter dorsal root ganglion
      neurons in culture, i. e., to produce an increase in number of spikes and a
      decrease in latency to firing during a ramped depolarizing stimulus. These
      effects were blocked by propranolol. Furthermore epinephrine, like several other
      direct-acting hyperalgesic agents, caused a potentiation of tetrodotoxin
      resistant sodium current, an effect that was abolished by Rp-adenosine 3',5'
      cyclic monophosphate and significantly attenuated by bisindolylmaleimide.
      Isoproterenol also potentiated tetrodotoxin-resistant sodium current. In
      conclusion, epinephrine produces cutaneous mechanical hyperalgesia and sensitizes
      cultured dorsal root ganglion neurons in the absence of nerve injury via an
      action at a beta-adrenergic receptor. These effects of epinephrine are mediated
      by both the protein kinase A and protein kinase C second-messenger pathways.

PMID- 10085338
TI  - Central processing of pulsed pheromone signals by antennal lobe neurons in the
      male moth Agrotis segetum.
AB  - Male moths use female-produced pheromones as orientation cues during the mate
      finding process. In addition to the needs of evaluating the quality and quantity
      of the pheromone signal, the male moth also needs to resolve the filamentous
      structure of the pheromone plume to proceed toward the releasing point
      successfully. To understand how a discontinuous olfactory signal is processed at
      the central level, we used intracellular recording methods to characterize the
      response patterns of antennal lobe (AL) neurons to pulsatile stimulation with the
      full female-produced pheromone blend and its single components in male turnip
      moths, Agrotis segetum. Air puffs delivered at frequencies of 1, 3, 5, 7, or 10
      Hz were used to carry the stimulus. Two types of AL neurons were characterized
      according to their capabilities to resolve stimulus pulses. The most common type
      could resolve at least 1-Hz pulses, thus termed fast neurons; another type could
      not resolve any pulses, thus termed slow neurons. When fast neurons were excited
      by stimuli, they always displayed biphasic response patterns, a depolarization
      phase followed by a hyperpolarization phase. This pattern could be evoked by
      stimulation with both the single pheromone components and the blend. The pulse
      resolving capability of the fast neurons correlated significantly with the size
      of the hyperpolarization phase. When the amplitude was higher and the fall time
      of the hyperpolarization faster, the neuron could follow more pulses per second.
      Moreover, interactions between different pheromone components eliciting different
      response patterns did not improve the pulse-resolving capability of fast neurons.

PMID- 10085339
TI  - Voltage-dependent sodium and calcium currents in acutely isolated adult rat
      trigeminal root ganglion neurons.
AB  - Voltage-dependent sodium (INa) and calcium (ICa) currents in small (<30 microM)
      neurons from adult rat trigeminal root ganglia were characterized with a standard
      whole cell patch-clamp technique. Two types of INa showing different sensitivity
      to tetrodotoxin (TTX) were recorded, which showed marked differences in their
      activating and inactivating time courses. The activation and the steady-state
      inactivation kinetics of TTX-resistant INa were more depolarized by about +20 and
      +30 mV, respectively, than those of TTX-sensitive INa. Voltage-dependent ICa was
      recorded under the condition that suppressed sodium and potassium currents with
      10 mM Ca2+ as a charge carrier. Depolarizing step pulses from a holding potential
      of -80 mV evoked two distinct inward ICa, low-voltage activated (LVA) and high
      voltage activated (HVA) ICa. LVA ICa was first observed at -60 to -50 mV and
      reached a peak at about -30 mV. Amiloride (0.5 mM) suppressed approximately 60%
      of the LVA ICa, whereas approximately 10% of HVA ICa was inhibited by the same
      concentration of the amiloride. LVA ICa was far less affected by the presence of
      external Cd2+ or the replacement of Ca2+ by 10 Ba2+ than HVA ICa. The omega
      conotoxin GVIA (omega-CgTx), an N-type ICa blocker, suppressed approximately 65%
      of the whole cell HVA ICa at the concentration of 1 microM. The omega-CgTx
      resistant HVA ICa was sensitive to nifedipine (10 microM), a dihydropyridine
      (DHP) calcium channel antagonist, which produced an additional blockade by
      approximately 25% of the drug-free control ( approximately 70% of the omega-CgTx
      resistant ICa). The combination of 10 microM nifedipine and 1 microM omega-CgTx
      left approximately 13% of the drug-free control ICa unblocked. The DHP agonist S(
      )-BayK8644 (5 microM) shifted the activation of the HVA ICa to more negative
      potentials and increased its maximal amplitude. Additionally, S(-)-BayK8644
      caused the appearance of a slowed component of the tail current. These results
      clearly demonstrate that the presence of two types of sodium channels, TTX
      sensitive and resistant, and three types of calcium channels, T, L, and N type,
      in the small-sized adult rat trigeminal ganglion neurons.

PMID- 10085340
TI  - Quantal secretion and nerve-terminal cable properties at neuromuscular junctions
      in an amphibian (Bufo marinus).
AB  - The effect of a conditioning depolarizing current pulse (80-200 micros) on
      quantal secretion evoked by a similar test pulse at another site was examined in
      visualized motor-nerve terminal branches of amphibian endplates (Bufo marinus).
      Tetrodotoxin (200 nM) and cadmium (50 microM) were used to block voltage
      dependent sodium and calcium conductances. Quantal release at the test electrode
      was depressed at different distances (28-135 microm) from the conditioning
      electrode when the conditioning and test pulses were delivered simultaneously.
      This depression decreased when the interval between conditioning and test current
      pulses was increased, until, at an interval of approximately 0.25 ms, it was
      negligible. At no time during several thousand test-conditioning pairs, for
      electrodes at different distances apart (28-135 microm) on the same or contiguous
      terminal branches, did the electrotonic effects of quantal release at one
      electrode produce quantal release at the other. Analytic and numerical solutions
      were obtained for the distribution of transmembrane potential at different sites
      along terminal branches of different lengths for current injection at a point on
      a terminal branch wrapped in Schwann cell, in the absence of active membrane
      conductances. Solutions were also obtained for the combined effects of two sites
      of current injection separated by different time delays. This cable model shows
      that depolarizing current injections of a few hundred microseconds duration
      produce hyperpolarizations at approximately 30 microm beyond the site of current
      injection, with these becoming larger and occurring at shorter distances the
      shorter the terminal branch. Thus the effect of a conditioning depolarizing pulse
      at one site on a subsequent test pulse at another more than approximately 30
      microm away is to substantially decrease the absolute depolarization produced by
      the latter, provided the interval between the pulses is less than a few hundred
      microseconds. It is concluded that the passive cable properties of motor nerve
      terminal branches are sufficient to explain the effects on quantal secretion by a
      test electrode depolarization of current injections from a spatially removed
      conditioning electrode.

PMID- 10085341
TI  - Increased intracellular calcium in rat anterior piriform cortex in response to
      threonine after threonine deprivation.
AB  - The anterior piriform cortex (APC) may serve as the chemosensor for amino acid
      (AA) deficiency in rats. To investigate the mechanism by which the APC recognizes
      a limiting indispensable AA (IAA), we examined changes in intracellular calcium
      ([Ca2+]i) in APC slices after culture in medium with or without threonine (Thr)
      or lysine (Lys). The addition of 1 or 10 mM Thr to slices previously incubated in
      Thr-devoid medium resulted in a significant and sustained increase in [Ca2+]i
      compared to control slices; an effect not seen when isoleucine, another IAA, was
      added. Similar results were seen when lysine, but not threonine, was added to
      slices incubated in lysine-devoid medium. The rise in [Ca2+]i resulting from the
      addition of the limiting IAA to deficient slices may be linked to enhanced
      activity of the appropriate AA transporter. This is suggested by preliminary
      findings that serine, a small neutral AA that uses the same transporter as
      threonine, gave rise to an enhanced response in the Thr-deficient slice.

PMID- 10085342
TI  - Patterns of phrenic motor output evoked by chemical stimulation of neurons
      located in the pre-Botzinger complex in vivo.
AB  - The pre-Botzinger complex (pre-BotC) has been proposed to be essential for
      respiratory rhythm generation from work in vitro. Much less, however, is known
      about its role in the generation and modulation of respiratory rhythm in vivo.
      Therefore we examined whether chemical stimulation of the in vivo pre-BotC
      manifests respiratory modulation consistent with a respiratory rhythm generator.
      In chloralose- or chloralose/urethan-anesthetized, vagotomized cats, we recorded
      phrenic nerve discharge and arterial blood pressure in response to chemical
      stimulation of neurons located in the pre-BotC with DL-homocysteic acid (DLH; 10
      mM; 21 nl). In 115 of the 122 sites examined in the pre-BotC, unilateral
      microinjection of DLH produced an increase in phrenic nerve discharge that was
      characterized by one of the following changes in cycle timing and pattern: 1) a
      rapid series of high-amplitude, rapid rate of rise, short-duration bursts, 2)
      tonic excitation (with or without respiratory oscillations), 3) an integration of
      the first two types of responses (i.e., tonic excitation with high-amplitude,
      short-duration bursts superimposed), or 4) augmented bursts in the phrenic
      neurogram (i.e., eupneic breath ending with a high-amplitude, short-duration
      burst). In 107 of these sites, the phrenic neurogram response was accompanied by
      an increase or decrease (>/=10 mmHg) in arterial blood pressure. Thus increases
      in respiratory burst frequency and production of tonic discharge of inspiratory
      output, both of which have been seen in vitro, as well as modulation of burst
      pattern can be produced by local perturbations of excitatory amino acid
      neurotransmission in the pre-BotC in vivo. These findings are consistent with the
      proposed role of this region as the locus for respiratory rhythm generation.

PMID- 10085343
TI  - Development of acetylcholine-induced responses in neonatal gerbil outer hair
      cells.
AB  - Cochlear outer hair cells (OHCs) are dominantly innervated by efferents, with
      acetylcholine (ACh) being their principal neurotransmitter. ACh activation of the
      cholinergic receptors on isolated OHCs induces calcium influx through the
      ionotropic receptors, followed by a large outward K+ current through nearby Ca2+
      activated K+ channels. The outward K+ current hyperpolarizes the cell, resulting
      in the fast inhibitory effects of efferent action. Although the ACh receptors
      (AChRs) in adult OHCs have been identified and the ACh-induced current responses
      have been characterized, it is unclear when the ACh-induced current responses
      occur during development. In this study we attempt to address this question by
      determining the time of onset of the ACh-induced currents in neonatal gerbil
      OHCs, using whole cell patch-clamp techniques. Developing gerbils ranging in age
      from 4 to 12 days were used in these experiments, because efferent synaptogenesis
      and functional maturation of OHCs occur after birth. Results show that the first
      detectable ACh-induced current occurred at 6 days after birth (DAB) in 12% of the
      basal turn cells with a small outward current. The fraction of responsive cells
      and the size of outward currents increased as development progressed. By 11 DAB,
      the fraction of responsive cells and the current size were comparable with those
      of adult OHCs. The results indicate that the maturation of the ACh-induced
      response begins around 6 DAB. It appears that the development of ACh-induced
      responses occur during the same time period when OHCs develop motility but before
      the onset of auditory function, which is around 12 DAB when cochlear microphonic
      potentials can first be evoked with acoustic stimulation in gerbils.

PMID- 10085344
TI  - Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the
      rat barrel cortex.
AB  - We have used whole cell recording in the anesthetized rat to study whisker-evoked
      synaptic and spiking responses of single neurons in the barrel cortex. On the
      basis of their intrinsic firing patterns, neurons could be classified as either
      regular-spiking (RS) cells, intrinsically burst-spiking (IB) cells, or fast
      spiking (FS) cells. Some recordings responded to current injection with a complex
      spike pattern characteristic of apical dendrites. All cell types had high rates
      of spontaneous postsynaptic potentials, both excitatory (EPSPs) and inhibitory
      (IPSPs). Some spontaneous EPSPs reached threshold, and these typically elicited
      only single action potentials in RS cells, bursts of action potentials in FS
      cells and IB cells, and a small, fast spike or a complex spike in dendrites.
      Deflection of single whiskers evoked a fast initial EPSP, a prolonged IPSP, and
      delayed EPSPs in all cell types. The intrinsic firing pattern of cells predicted
      their short-latency whisker-evoked spiking patterns. All cell types responded
      best to one or, occasionally, two primary whiskers, but typically 6-15
      surrounding whiskers also generated significant synaptic responses. The initial
      EPSP had a relatively fixed amplitude and latency, and its amplitude in response
      to first-order surrounding whiskers was approximately 55% of that induced by the
      primary whisker. Second- and third-order surrounding whiskers evoked responses of
      approximately 27 and 12%, respectively. The latency of the initial EPSP was
      shortest for the primary whiskers, longer for surrounding whiskers, and varied
      with the neurons' depth below the pia. EPSP latency was shortest in the granular
      layer, longer in supragranular layers, and longest in infragranular layers. The
      receptive field size, defined as the total number of fast EPSP-inducing whiskers,
      was independent of each cell's intrinsic firing type, its subpial depth, or the
      whisker stimulus parameters. On average, receptive fields included >10 whiskers.
      Our results show that single neurons integrate rapid synaptic responses from a
      large proportion of the mystacial vibrissae, and suggest that the whisker-evoked
      responses of barrel neurons are a function of both synaptic inputs and intrinsic
      membrane properties.

PMID- 10085345
TI  - Tonic activation of presynaptic GABAB receptors in the opener neuromuscular
      junction of crayfish.
AB  - Release of excitatory transmitter from boutons on crayfish nerve terminals was
      inhibited by (R,S)-baclofen, an agonist at GABAB receptors. Baclofen had no
      postsynaptic actions as it reduced quantal content without affecting quantal
      amplitude. The effect of baclofen increased with concentration producing 18%
      inhibition at 10 microM; EC50, 50% inhibition at 30 microM; maximal inhibition,
      85% at 100 microM and higher. There was no desensitization, even with 200 or 320
      microM baclofen. Phaclofen, an antagonist at GABAB receptors, competitively
      antagonized the inhibitory action of baclofen (KD = 50 microM, equivalent to a
      pA2 = 4.3 +/- 0.1). Phaclofen on its own at concentrations below 200 microM had
      no effect on release, whereas at 200 microM phaclofen itself increased the
      control level of release by 60%, as did 2-hydroxy-saclofen (200 microM), another
      antagonist at GABAB receptors. This increase was evidently due to antagonism of a
      persistent level of GABA in the synaptic cleft, since the effect was abolished by
      destruction of the presynaptic inhibitory fiber, using intra-axonal pronase. We
      conclude that presynaptic GABAB receptors, with a pharmacological profile similar
      to that of mammalian GABAB receptors, are involved in the control of transmitter
      release at the crayfish neuromuscular junction.

PMID- 10085346
TI  - Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing
      responses in hippocampal pyramidal cells.
AB  - Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant
      activity. GABA uptake inhibitors are believed to produce their anticonvulsant
      effects by prolonging the postsynaptic actions of GABA, released during episodes
      of neuronal hyperexcitability. However, tiagabine has recently been reported to
      facilitate the depolarizing actions of GABA in the CNS of adult rats following
      the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic
      interneuronal activation during epileptiform activity. In the present study, we
      performed extracellular and whole cell recordings from CA1 pyramidal neurons in
      rat hippocampal slices to examine the functional consequences of tiagabine
      augmented GABA-mediated depolarizing responses. Orthodromic population spikes
      (PSs), elicited from the stratum radiatum, were inhibited following the
      activation of recurrent inhibitory pathways by antidromic conditioning
      stimulation of the alveus, which consisted of either a single stimulus or a train
      of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of
      orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which
      was always of much greater strength and duration than that produced by a single
      conditioning stimulus, was greatly enhanced following the bath application of
      tiagabine (2-100 microM). Thus, in the presence of tiagabine (20 microM),
      orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 +/-
      2.6% (mean +/- SE) and 34.4 +/- 18.5% of their unconditioned amplitudes compared
      with only 35.4 +/- 12.7% and 98.8 +/- 12.4% in control. Whole cell recordings
      revealed that the bath application of tiagabine (20 microM) either caused the
      appearance or greatly enhanced the amplitude of GABA-mediated depolarizing
      responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum
      radiatum at time points that coincided with the DR were inhibited to below the
      threshold for action-potential firing. Independently of the stimulus intensity
      with which they were evoked, the charge transferred to the soma by excitatory
      postsynaptic currents (EPSCs), elicited in the presence of tiagabine (20 microM)
      during the large (1,428 +/- 331 pA) inward currents that underlie the DRs, was
      decreased on the average by 90.8 +/- 1.7%. Such inhibition occurred despite the
      presence of the GABAB receptor antagonist, CGP 52 432 (10 microM), indicating
      that GABAB heteroreceptors, located on glutamatergic terminals, do not mediate
      the observed reduction in the amplitude of excitatory postsynaptic responses. The
      present results suggest that despite facilitating the induction of GABA-mediated
      depolarizations, tiagabine application may nevertheless increase the
      effectiveness of synaptic inhibition during the synchronous high-frequency
      activation of inhibitory interneurons by enhanced shunting.

PMID- 10085347
TI  - Projections and firing properties of down eye-movement neurons in the
      interstitial nucleus of Cajal in the cat.
AB  - To clarify the role of the interstitial nucleus of Cajal (INC) in the control of
      vertical eye movements, projections of burst-tonic and tonic neurons in and
      around the INC were studied. This paper describes neurons with downward ON
      directions. We examined, by antidromic activation, whether these down INC (d-INC)
      neurons contribute to two pathways: a commissural pathway to the contralateral (c
      ) INC and a descending pathway to the ipsilateral vestibular nucleus (i-VN).
      Stimulation of the two pathways showed that as many as 74% of neurons were
      activated antidromically from one of the pathways. Of 113 d-INC neurons tested,
      44 were activated from the commissural pathway and 40 from the descending
      pathway. No neurons were activated from both pathways. We concluded that
      commissural and descending pathways from the INC originate from two separate
      groups of neurons. Tracking of antidromic microstimulation in the two nuclei
      revealed multiple low-threshold sites and varied latencies; this was interpreted
      as a sign of existence of axonal arborization. Neurons with commissural
      projections tended to be located more dorsally than those with descending
      projections. Neurons with descending projections had significantly greater eye
      position sensitivity and smaller saccadic sensitivity than neurons with
      commissural projections. The two groups of INC neurons increased their firing
      rate in nose-up head rotations and responded best to the rotation in the plane of
      contralateral posterior/ipsilateral anterior canal pair. Neurons with commissural
      projections showed a larger phase lag of response to sinusoidal rotation (54.6 +/
      7.6 degrees ) than neurons with descending projections (45.0 +/- 5.5 degrees ).
      Most neurons with descending projections received disynaptic excitation from the
      contralateral vestibular nerve. Neurons with commissural projections rarely
      received such disynaptic input. We suggest that downward-position-vestibular
      (DPV) neurons in the VN and VN-projecting d-INC neurons form a loop, together
      with possible commissural loops linking the bilateral VNs and the bilateral INCs.
      By comparing the quantitative measures of d-INC neurons with those of DPV
      neurons, we further suggest that integration of head velocity signals proceeds
      from DPV neurons to d-INC neurons with descending projections and then to d-INC
      neurons with commissural projections, whereas saccadic velocity signals are
      processed in the reverse order.

PMID- 10085348
TI  - Inhibitory contributions to spatiotemporal receptive-field structure and
      direction selectivity in simple cells of cat area 17.
AB  - Intracortical inhibition contributes to direction selectivity in primary visual
      cortex, but how it acts has been unclear. We investigated this problem in simple
      cells of cat area 17 by taking advantage of the link between spatiotemporal (S-T)
      receptive-field structure and direction selectivity. Most cells in layer 4 have S
      T-oriented receptive fields in which gradients of response timing across the
      field confer a preferred direction of motion. Linear summation of responses
      across the receptive field, followed by a static nonlinear amplification, has
      been shown previously to account for directional tuning in layer 4. We tested the
      hypotheses that inhibition acts by altering S-T structure or the static
      nonlinearity or both. Drifting and counterphasing sine wave gratings were used to
      measure direction selectivity and S-T structure, respectively, in 17 layer 4
      simple cells before and during iontophoresis of bicuculline methiodide (BMI), a
      GABAA antagonist. S-T orientation was quantified from fits to response temporal
      phase versus stimulus spatial phase data. Bicuculline reduced direction
      selectivity and S-T orientation in nearly all cells, and reductions in the two
      measures were well correlated (r = 0.81) and reversible. Using conventional
      linear predictions based on response phase and amplitude, we found that BMI
      induced changes in S-T structure also accounted well for absolute changes in the
      amplitude and phase of responses to gratings drifting in the preferred and
      nonpreferred direction. For each cell we also calculated an exponent used to
      estimate the static nonlinearity. Bicuculline reduced the exponent in most cells,
      but the changes were not correlated with reductions in direction selectivity. We
      conclude that GABAA-mediated inhibition influences directional tuning in layer 4
      primarily by sculpting S-T receptive-field structure. The source of the
      inhibition is likely to be other simple cells with certain spatiotemporal
      relationships to their target. Despite reductions in the two measures, most
      receptive fields maintained some directional tuning and S-T orientation during
      BMI. This suggests that their excitatory inputs, arising from the lateral
      geniculate nucleus and within area 17, are sufficient to create some S-T
      orientation and that inhibition accentuates it. Finally, BMI also reduced
      direction selectivity in 8 of 10 simple cells tested in layer 6, but the
      reductions were not accompanied by systematic changes in S-T structure. This
      reflects the fact that S-T orientation, as revealed by our first-order measures
      of the receptive field, is weak there normally. Inhibition likely affects layer 6
      cells via more complex, nonlinear interactions.

PMID- 10085349
TI  - Role of presynaptic L-type Ca2+ channels in GABAergic synaptic transmission in
      cultured hippocampal neurons.
AB  - Using dual whole cell patch-clamp recordings of monosynaptic GABAergic inhibitory
      postsynaptic currents (IPSCs) in cultured rat hippocampal neurons, we have
      previously demonstrated posttetanic potentiation (PTP) of IPSCs. Tetanic
      stimulation of the GABAergic neuron leads to accumulation of Ca2+ in the
      presynaptic terminals. This enhances the probability of GABA-vesicle release for
      up to 1 min, which underlies PTP. In the present study, we have examined the
      effect of altering the probability of release on PTP of IPSCs. Baclofen (10
      microM), which depresses presynaptic Ca2+ entry through N- and P/Q-type voltage
      dependent Ca2+ channels (VDCCs), caused a threefold greater enhancement of PTP
      than did reducing [Ca2+]o to 1.2 mM, which causes a nonspecific reduction in Ca2+
      entry. This finding prompted us to investigate whether presynaptic L-type VDCCs
      contribute to the Ca2+ accumulation in the boutons during spike activity. The L
      type VDCC antagonist, nifedipine (10 microM), had no effect on single IPSCs
      evoked at 0.2 Hz but reduced the PTP evoked by a train of 40 Hz for 2 s by 60%.
      Another L-type VDCC antagonist, isradipine (5 microM), similarly inhibited PTP by
      65%. Both L-type VDCC blockers also depressed IPSCs during the stimulation (i.e.,
      they increased tetanic depression). The L-type VDCC "agonist" (-)BayK 8644 (4
      microM) had no effect on PTP evoked by a train of 40 Hz for 2 s, which probably
      saturated the PTP process, but enhanced PTP evoked by a train of 1 s by 91%. In
      conclusion, the results indicate that L-type VDCCs do not participate in low
      frequency synchronous transmitter release, but contribute to presynaptic Ca2+
      accumulation during high-frequency activity. This helps maintain vesicle release
      during tetanic stimulation and also enhances the probability of transmitter
      release during the posttetanic period, which is manifest as PTP. Involvement of L
      type channels in these processes represents a novel presynaptic regulatory
      mechanism at fast CNS synapses.

PMID- 10085350
TI  - Coherent oscillations in membrane potential synchronize impulse bursts in central
      olfactory neurons of the crayfish.
AB  - Lateral protocerebral interneurons (LPIs) in the central olfactory pathway of the
      freshwater crayfish Procambarus clarkii reside within the lateral protocerebrum
      and receive direct input from projection neurons of the olfactory midbrain. The
      LPIs exhibit periodic (0.5 Hz) changes in membrane potential that are imposed on
      them synaptically. Acute surgical experiments indicate that the synaptic activity
      originates from a group of oscillatory neurons lying within the lateral
      protocerebrum. Simultaneous intracellular recordings from many LPI pairs indicate
      that this periodic synaptic input is synchronous and coherent among the
      population of approximately 200 LPIs on each side of the brain. In many LPIs,
      specific odors applied to antennules in isolated head preparations generate long
      lasting excitatory postsynaptic potentials and impulse bursts. The impulse bursts
      are generated only near the peaks of the ongoing depolarizations, approximately 1
      s after stimulus application, and so the periodic baseline activity is
      instrumental in timing burst generation. Simultaneous recordings from pairs of
      LPIs show that, when impulse bursts occur in both cells after an odorant
      stimulus, they are synchronized by the common periodic depolarizations. We
      conclude that the common, periodic activity in LPIs can synchronize impulse
      bursts in subsets of these neurons, possibly generating powerful long-lasting
      postsynaptic effects in downstream target neurons.

PMID- 10085351
TI  - Properties of conditioned abducens nerve responses in a highly reduced in vitro
      brain stem preparation from the turtle.
AB  - Previous work suggested that the cerebellum and red nucleus are not necessary for
      the acquisition, extinction, and reacquistion of the in vitro classically
      conditioned abducens nerve response in the turtle. These findings are extended in
      the present study by obtaining conditioned responses (CRs) in preparations that
      received a partial ablation of the brain stem circuitry. In addition to removing
      all tissue rostral to and including the midbrain and cerebellum, a transection
      was made just caudal to the emergence of the IXth nerve. Such ablations result in
      a 4-mm-thick section of brain stem tissue that functionally eliminates the
      sustained component of the unconditioned response (UR) while leaving only a
      phasic component. We refer to this region of brain stem tissue caudal to the IXth
      nerve as the "caudal premotor blink region." Neural discharge was recorded from
      the abducens nerve following a single shock unconditioned stimulus (US) applied
      to the ipsilateral trigeminal nerve. When the US was paired with a conditioned
      stimulus (CS) applied to the posterior eighth, or auditory, nerve using a delay
      conditioning paradigm, a positive slope of CR acquisition was recorded in the
      abducens nerve, and CR extinction was recorded when the stimuli were alternated.
      Resumption of paired stimuli resulted in reacquisition. Quantitative analysis of
      the CRs in preparations in which the caudal premotor blink region had been
      removed and those with cerebellar/red nucleus lesions showed that both types of
      preparations had abnormally short latency CR onsets compared with preparations in
      which these regions were intact. Preparations with brain stem transections had
      significantly earlier CR offsets as more CRs terminated as short bursts when
      compared with intact or cerebellar lesioned preparations. These data suggest that
      a highly reduced in vitro brain stem preparation from the turtle can be
      classically conditioned. Furthermore, the caudal brain stem is not a site of
      acquisition in this reduced preparation, but it contributes to the sustained
      activity of both the UR and CR. Finally, the unusually short CR onset latencies
      following lesions to the cerebellum are not further exacerbated by removal of the
      caudal brain stem. These studies suggest that convergence of CS and US synaptic
      inputs onto the abducens nerve reflex circuitry may underlie acquisition in this
      reduced preparation, but that mechanisms that control learned CR timing arise
      from the cerebellorubral system.

PMID- 10085352
TI  - Characterization of the Aplysia californica cerebral ganglion F cluster.
AB  - The cerebral ganglia neurons of Aplysia californica are involved in the
      development and modulation of many behaviors. The medially located F cluster has
      been characterized using morphological, electrophysiological and biochemical
      techniques and contains at least three previously uncharacterized neuronal
      population. As the three subtypes are located in three distinct layers, they are
      designated as top, middle, and bottom layer F-cluster neurons (CFT, CFM, and
      CFB). The CFT cells are large (92 +/- 25 microm), white, nonuniformly shaped, and
      located partially in the sheath surrounding the ganglion. These neurons exhibit
      weak electrical coupling, the presence of synchronized spontaneous changes in
      membrane potential, and a generalized inhibitory input upon electrical
      stimulation of the anterior tentacular (AT) nerve. Similar to the CFT neurons,
      the CFM neurons (46 +/- 12 microm) are mainly silent but do not show electrical
      coupling or synchronized changes in membrane potential. Unlike the CFT neurons,
      the CFM neurons exhibit weak action potential broadening during constant current
      injection. Comparison of the peptide profiles of CFT, CFM, and CFB (10-30 microm)
      neurons using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry demonstrates distinct peptide molecular weights for each neuronal
      subtype with the masses of these peptides not matching any previously
      characterized peptides from A. californica. The mass spectra obtained from the AT
      nerve are similar to the CFT neuron mass spectra, while upper labial nerve
      contains many peptides observed in the CFM neurons located in nongranular neuron
      region.

PMID- 10085353
TI  - Electrophysiological and behavioral analysis of lip touch as a component of the
      food stimulus in the snail Lymnaea.
AB  - Electrophysiological and video recording methods were used to investigate the
      function of lip touch in feeding ingestion behavior of the pond snail Lymnaea
      stagnalis. Although this stimulus was used successfully as a conditioning
      stimulus (CS) in appetitive learning experiments, the detailed role of lip touch
      as a component of the sensory stimulus provided by food in unconditioned feeding
      behavior was never ascertained. Synaptic responses to lip touch in identified
      feeding motoneurons, central pattern generator interneurons, and modulatory
      interneurons were recorded by intracellular electrodes in a semi-intact
      preparation. We showed that touch evoked a complex but characteristic sequence of
      synaptic inputs on each neuron type. Touch never simply activated feeding cycles
      but provided different types of synaptic input, determined by the feeding phase
      in which the neuron was normally active in the rhythmic feeding cycle. The
      tactile stimulus evoked mainly inhibitory synaptic inputs in protraction-phase
      neurons and excitation in rasp-phase neurons. Swallow-phase neurons were also
      excited after some delay, suggesting that touch first reinforces the rasp then
      swallow phase. Video analysis of freely feeding animals demonstrated that during
      normal ingestion of a solid food flake the food is drawn across the lips
      throughout the rasp phase and swallow phase and therefore provides a tactile
      stimulus during both these retraction phases of the feeding cycle. The tactile
      component of the food stimulus is strongest during the rasp phase when the lips
      are actively pressed onto the substrate that is being moved across them by the
      radula. By using a semi-intact preparation we demonstrated that application of
      touch to the lips during the rasp phase of a sucrose-driven fictive feeding
      rhythm increases both the regularity and frequency of rasp-phase motoneuron
      firing compared with sucrose applied alone.

PMID- 10085354
TI  - Bursting in inhibitory interneuronal networks: A role for gap-junctional
      coupling.
AB  - Much work now emphasizes the concept that interneuronal networks play critical
      roles in generating synchronized, oscillatory behavior. Experimental work has
      shown that functional inhibitory networks alone can produce synchronized
      activity, and theoretical work has demonstrated how synchrony could occur in
      mutually inhibitory networks. Even though gap junctions are known to exist
      between interneurons, their role is far from clear. We present a mechanism by
      which synchronized bursting can be produced in a minimal network of mutually
      inhibitory and gap-junctionally coupled neurons. The bursting relies on the
      presence of persistent sodium and slowly inactivating potassium currents in the
      individual neurons. Both GABAA inhibitory currents and gap-junctional coupling
      are required for stable bursting behavior to be obtained. Typically, the role of
      gap-junctional coupling is focused on synchronization mechanisms. However, these
      results suggest that a possible role of gap-junctional coupling may lie in the
      generation and stabilization of bursting oscillatory behavior.

PMID- 10085355
TI  - Action of the brain stem saccade generator during horizontal gaze shifts. I.
      Discharge patterns of omnidirectional pause neurons.
AB  - Omnidirectional pause neurons (OPNs) pause for the duration of a saccade in all
      directions because they are part of the neural mechanism that controls saccade
      duration. In the natural situation, however, large saccades are accompanied by
      head movements to produce rapid gaze shifts. To determine whether OPNs are part
      of the mechanism that controls the whole gaze shift rather than the eye saccade
      alone, we monitored the activity of 44 OPNs that paused for rightward and
      leftward gaze shifts but otherwise discharged at relatively constant average
      rates. Pause duration was well correlated with the duration of either eye or gaze
      movement but poorly correlated with the duration of head movement. The time of
      pause onset was aligned tightly with the onset of either eye or gaze movement but
      only loosely aligned with the onset of head movement. These data suggest that the
      OPN pause does not encode the duration of head movement. Further, the end of the
      OPN pause was often better aligned with the end of the eye movement than with the
      end of the gaze movement for individual gaze shifts. For most gaze shifts, the
      eye component ended with an immediate counterrotation owing to the
      vestibuloocular reflex (VOR), and gaze ended at variable times thereafter. In
      those gaze shifts where eye counterrotation was delayed, the end of the pause
      also was delayed. Taken together, these data suggest that the end of the pause
      influences the onset of eye counterrotation, not the end of the gaze shift. We
      suggest that OPN neurons act to control only that portion of the gaze movement
      that is commanded by the eye burst generator. This command is expressed by
      driving the saccadic eye movement directly and also by suppressing VOR eye
      counterrotation. Because gaze end is less well correlated with pause end and
      often occurs well after counterrotation onset, we conclude that elements of the
      burst generator typically are not active till gaze end, and that gaze end is
      determined by another mechanism independent of the OPNs.

PMID- 10085356
TI  - Intrinsic theta-frequency membrane potential oscillations in hippocampal CA1
      interneurons of stratum lacunosum-moleculare.
AB  - The ionic conductances underlying membrane potential oscillations of hippocampal
      CA1 interneurons located near the border between stratum lacunosum-moleculare and
      stratum radiatum (LM) were investigated using whole cell current-clamp recordings
      in rat hippocampal slices. At 22 degrees C, when LM cells were depolarized near
      spike threshold by current injection, 91% of cells displayed 2-5 Hz oscillations
      in membrane potential, which caused rhythmic firing. At 32 degrees C, mean
      oscillation frequency increased to 7.1 Hz. Oscillations were voltage dependent
      and were eliminated by hyperpolarizing cells 6-10 mV below spike threshold.
      Blockade of ionotropic glutamate and GABA synaptic transmission did not affect
      oscillations, indicating that they were not synaptically driven. Oscillations
      were eliminated by tetrodotoxin, suggesting that Na+ currents generate the
      depolarizing phase of oscillations. Oscillations were not affected by blocking
      Ca2+ currents with Cd2+ or Ca2+-free ACSF or by blocking the hyperpolarization
      activated current (Ih) with Cs+. Both Ba2+ and a low concentration of 4
      aminopyridine (4-AP) reduced oscillations but TEA did not. Theta-frequency
      oscillations were much less common in interneurons located in stratum oriens.
      Intrinsic membrane potential oscillations in LM cells of the CA1 region thus
      involve an interplay between inward Na+ currents and outward K+ currents
      sensitive to Ba2+ and 4-AP. These oscillations may participate in rhythmic
      inhibition and synchronization of pyramidal neurons during theta activity in
      vivo.

PMID- 10085357
TI  - Metabotropic glutamate receptor modulation of glutamate responses in the
      suprachiasmatic nucleus.
AB  - Glutamate is the primary excitatory transmitter in the suprachiasmatic nucleus
      (SCN). Ionotropic glutamate receptors (iGluRs) mediate transduction of light
      information from the retina to the SCN, an important circadian clock phase
      shifting pathway. Metabotropic glutamate receptors (mGluRs) may play a
      significant modulatory role. mGluR modulation of SCN responses to glutamate was
      investigated with fura-2 calcium imaging in SCN explant cultures. SCN neurons
      showed reproducible calcium responses to glutamate, kainate, and N-methyl-D
      aspartate (NMDA). Although the type I/II mGluR agonists L-CCG-I and t-ACPD did
      not evoke calcium responses, they did inhibit kainate- and NMDA-evoked calcium
      rises. This interaction was insensitive to pertussis toxin. Protein kinase A
      (PKA) activation by 8-bromo-cAMP significantly reduced iGluR inhibition by mGluR
      agonists. The inhibitory effect of mGluRs was enhanced by activating protein
      kinase C (PKC) and significantly reduced in the presence of the PKC inhibitor H7.
      Previous reports show that L-type calcium channels can be modulated by PKC and
      PKA. In SCN cells, about one-half of the calcium rise evoked by kainate or NMDA
      was blocked by the L-type calcium channel antagonist nimodipine. Calcium rises
      evoked by K+ were used to test whether mGluR inhibition of iGluR calcium rises
      involved calcium channel modulation. These calcium rises were primarily
      attributable to activation of voltage-activated calcium channels. PKC activation
      inhibited K+-evoked calcium rises, but PKC inhibition did not affect L-CCG-I
      inhibition of these rises. In contrast, 8Br-cAMP had no effect alone but blocked
      L-CCG-I inhibition. Taken together, these results suggest that activation of
      mGluRs, likely type II, modulates glutamate-evoked calcium responses in SCN
      neurons. mGluR inhibition of iGluR calcium rises can be differentially influenced
      by PKC or PKA activation. Regulation of glutamate-mediated calcium influx could
      occur at L-type calcium channels, K+ channels, or at GluRs. It is proposed that
      mGluRs may be important regulators of glutamate responsivity in the circadian
      system.

PMID- 10085358
TI  - Interactive effects of the GABABergic modulation of calcium channels and calcium
      dependent potassium channels in lamprey.
AB  - The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in
      this study. Activation of GABAB receptors reduces calcium currents through both
      low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently
      results in the reduction of the calcium-dependent potassium (KCa) current. This
      in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We
      used the modulatory effects of GABAB receptor activation on N-methyl-D-aspartate
      (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental
      model in which to separate the effects of GABAB receptor activation on LVA
      calcium channels from that on KCa channels. We show experimentally and by using
      simulations that a direct effect on LVA calcium channels can account for the
      effects of GABAB receptor activation on intrinsic membrane potential oscillations
      to a larger extent than indirect effects mediated via KCa channels. Furthermore,
      by conducting experiments and simulations on intrinsic membrane potential
      oscillations, we find that KCa channels may be activated by calcium entering
      through LVA calcium channels, providing that the decay kinetics of the calcium
      that enters through LVA calcium channels is not as slow as the calcium entering
      via NMDA receptors. A combined experimental and computational analysis revealed
      that the LVA calcium current also contributes to neuronal firing properties.

PMID- 10085359
TI  - Dopamine activates two different receptors to produce variability in sign at an
      identified synapse.
AB  - Chemical synaptic transmission was investigated at a central synapse between
      identified neurons in the freshwater snail, Lymnaea stagnalis. The presynaptic
      neuron was the dopaminergic cell, Right Pedal Dorsal one (RPeD1). The
      postsynaptic neuron was Visceral Dorsal four (VD4). These neurons are components
      of the respiratory central pattern generator. The synapse from RPeD1 to VD4
      showed variability of sign, i.e., it was either inhibitory (monophasic and
      hyperpolarizing), biphasic (depolarizing followed by hyperpolarizing phases), or
      undetectable. Both the inhibitory and biphasic synapse were eliminated by low
      Ca2+/high Mg2+ saline and maintained in high Ca2+/high Mg2+ saline, indicating
      that these two types of connections were chemical and monosynaptic. The latency
      of the inhibitory postsynaptic potential (IPSP) in high Ca2+/high Mg2+ saline was
      approximately 43 ms, whereas the biphasic postsynaptic potential (BPSP) had
      approximately 12-ms latency in either normal or high Ca2+/high Mg2+ saline. For a
      given preparation, when dopamine was pressured applied to the soma of VD4, it
      always elicited the same response as the synaptic input from RPeD1. Thus, for a
      VD4 neuron receiving an IPSP from RPeD1, pressure application of dopamine to the
      soma of VD4 produced an inhibitory response similar to the IPSP. The reversal
      potentials of the IPSP and the inhibitory dopamine response were both
      approximately -90 mV. For a VD4 neuron with a biphasic input from RPeD1, pressure
      applied dopamine produced a biphasic response similar to the BPSP. The reversal
      potentials of the depolarizing phase of the BPSP and the biphasic dopamine
      response were both approximately -44 mV, whereas the reversal potentials for the
      hyperpolarizing phases were both approximately -90 mV. The hyperpolarizing but
      not the depolarizing phase of the BPSP and the biphasic dopamine response was
      blocked by the D-2 dopaminergic antagonist (+/-) sulpiride. Previously, our
      laboratory demonstrated that both IPSP and the inhibitory dopamine response are
      blocked by (+/-) sulpiride. Conversely, the depolarizing phase of both the BPSP
      and the biphasic dopamine response was blocked by the Cl- channel antagonist
      picrotoxin. Finally, both phases of the BPSP and the biphasic dopamine response
      were desensitized by continuous bath application of dopamine. These results
      indicate that the biphasic RPeD1 --> VD4 synapse is dopaminergic. Collectively,
      these data suggest that the variability in sign (inhibitory vs. biphasic) at the
      RPeD1 --> VD4 synapse is due to activation of two different dopamine receptors on
      the postsynaptic neuron VD4. This demonstrates that two populations of receptors
      can produce two different forms of transmission, i.e., the inhibitory and
      biphasic forms of the single RPeD1 --> VD4 synapse.

PMID- 10085360
TI  - Mechanisms underlying burst and regular spiking evoked by dendritic
      depolarization in layer 5 cortical pyramidal neurons.
AB  - Apical dendrites of layer 5 pyramidal cells in a slice preparation of rat
      sensorimotor cortex were depolarized focally by long-lasting glutamate
      iontophoresis while recording intracellularly from their soma. In most cells the
      firing pattern evoked by the smallest dendritic depolarization that evoked spikes
      consisted of repetitive bursts of action potentials. During larger dendritic
      depolarizations initial burst firing was followed by regular spiking. As
      dendritic depolarization was increased further the duration (but not the firing
      rate) of the regular spiking increased, and the duration of burst firing
      decreased. Depolarization of the soma in most of the same cells evoked only
      regular spiking. When the dendrite was depolarized to a critical level below
      spike threshold, intrasomatic current pulses or excitatory postsynaptic
      potentials also triggered bursts instead of single spikes. The bursts were driven
      by a delayed depolarization (DD) that was triggered in an all-or-none manner
      along with the first Na+ spike of the burst. Somatic voltage-clamp experiments
      indicated that the action current underlying the DD was generated in the dendrite
      and was Ca2+ dependent. Thus the burst firing was caused by a Na+ spike-linked
      dendritic Ca2+ spike, a mechanism that was available only when the dendrite was
      adequately depolarized. Larger dendritic depolarization that evoked late,
      constant-frequency regular spiking also evoked a long-lasting, Ca2+-dependent
      action potential (a "plateau"). The duration of the plateau but not its amplitude
      was increased by stronger dendritic depolarization. Burst-generating dendritic
      Ca2+ spikes could not be elicited during this plateau. Thus plateau initiation
      was responsible for the termination of burst firing and the generation of the
      constant-frequency regular spiking. We conclude that somatic and dendritic
      depolarization can elicit quite different firing patterns in the same pyramidal
      neuron. The burst and regular spiking observed during dendritic depolarization
      are caused by two types of Ca2+-dependent dendritic action potentials. We discuss
      some functional implications of these observations.

PMID- 10085361
TI  - Integration of proprioceptive and visual position-information: An experimentally
      supported model.
AB  - To localize one's hand, i.e., to find out its position with respect to the body,
      humans may use proprioceptive information or visual information or both. It is
      still not known how the CNS combines simultaneous proprioceptive and visual
      information. In this study, we investigate in what position in a horizontal plane
      a hand is localized on the basis of simultaneous proprioceptive and visual
      information and compare this to the positions in which it is localized on the
      basis of proprioception only and vision only. Seated at a table, subjects matched
      target positions on the table top with their unseen left hand under the table.
      The experiment consisted of three series. In each of these series, the target
      positions were presented in three conditions: by vision only, by proprioception
      only, or by both vision and proprioception. In one of the three series, the
      visual information was veridical. In the other two, it was modified by prisms
      that displaced the visual field to the left and to the right, respectively. The
      results show that the mean of the positions indicated in the condition with both
      vision and proprioception generally lies off the straight line through the means
      of the other two conditions. In most cases the mean lies on the side predicted by
      a model describing the integration of multisensory information. According to this
      model, the visual information and the proprioceptive information are weighted
      with direction-dependent weights, the weights being related to the direction
      dependent precision of the information in such a way that the available
      information is used very efficiently. Because the proposed model also can explain
      the unexpectedly small sizes of the variable errors in the localization of a seen
      hand that were reported earlier, there is strong evidence to support this model.
      The results imply that the CNS has knowledge about the direction-dependent
      precision of the proprioceptive and visual information.

PMID- 10085362
TI  - Electrophysiological properties of rat phrenic motoneurons during perinatal
      development.
AB  - Past studies determined that there is a critical period at approximately
      embryonic day (E)17 during which phrenic motoneurons (PMNs) undergo a number of
      pivotal developmental events, including the inception of functional recruitment
      via synaptic drive from medullary respiratory centers, contact with spinal
      afferent terminals, the completion of diaphragm innervation, and a major
      transformation of PMN morphology. The objective of this study was to test the
      hypothesis that there would be a marked maturation of motoneuron
      electrophysiological properties occurring in conjunction with these developmental
      processes. PMN properties were measured via whole cell patch recordings with a
      cervical slice-phrenic nerve preparation isolated from perinatal rats. From E16
      to postnatal day 1, there was a considerable transformation in a number of
      motoneuron properties, including 1) 10-mV increase in the hyperpolarization of
      the resting membrane potential, 2) threefold reduction in the input resistance,
      3) 12-mV increase in amplitude and 50% decrease duration of action potential, 4)
      major changes in the shapes of potassium- and calcium-mediated afterpotentials,
      5) decline in the prominence of calcium-dependent rebound depolarizations, and 6)
      increases in rheobase current and steady-state firing rates. Electrical coupling
      among PMNs was detected in 15-25% of recordings at all ages studied.
      Collectively, these data and those from parallel studies of PMN-diaphragm
      ontogeny describe how a multitude of regulatory mechanisms operate in concert
      during the embryonic development of a single mammalian neuromuscular system.

PMID- 10085363
TI  - Primary afferent fibers that contribute to increased substance P receptor
      internalization in the spinal cord after injury.
AB  - Upon noxious stimulation, substance P (SP) is released from primary afferent
      fibers into the spinal cord where it interacts with the SP receptor (SPR). The
      SPR is located throughout the dorsal horn and undergoes endocytosis after agonist
      binding, which provides a spatial image of SPR-containing neurons that undergo
      agonist interaction. Under normal conditions, SPR internalization occurs only in
      SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious
      stimulation. After nerve transection and inflammation, SPR immunoreactivity
      increases, and both noxious as well as nonnoxious stimulation produces SPR
      internalization in the superficial and deep dorsal horn. We investigated the
      primary afferent fibers that contribute to enhanced SPR internalization in the
      spinal cord after nerve transection and inflammation. Internalization evoked by
      electrical stimulation of the sciatic nerve was examined in untreated animals, at
      14 days after sciatic nerve transection or sham surgery and at 3 days after
      hindpaw inflammation. Electrical stimulation was delivered at intensities to
      excite Abeta fibers only, Abeta and Adelta fibers or A and C fibers as determined
      by the compound action potential recorded from the tibial nerve. Electrical
      stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min.
      Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5%
      increase in SPR and immunoreactivity in lamina I, respectively. Under normal
      conditions, stimulation of Adelta or C fibers evoked internalization that was
      confined to the superficial dorsal horn. After transection or inflammation, there
      was a 20-24% increase in the proportion of SPR+ lamina I neurons that exhibited
      internalization evoked by stimulation of Adelta fibers. The proportion of lamina
      I SPR+ neurons that exhibited internalization after stimulation of C-fibers was
      not altered by transection or inflammation because this was nearly maximal under
      normal conditions. Moreover, electrical stimulation sufficient to excite C fibers
      evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve
      transection and in 32-36% of SPR+ neurons in lamina III and IV after
      inflammation. Stimulation of Abeta fibers alone never evoked internalization in
      the superficial or deep dorsal horn. These results indicate that activation of
      small-caliber afferent fibers contributes to the enhanced SPR internalization in
      the spinal cord after nerve transection and inflammation and suggest that
      recruitment of neurons that possess the SPR contributes to hyperalgesia.

PMID- 10085364
TI  - Multiple neuropeptide Y receptors regulate K+ and Ca2+ channels in acutely
      isolated neurons from the rat arcuate nucleus.
AB  - We examined the effects of neuropeptide Y (NPY) and related peptides on Ca2+ and
      K+ currents in acutely isolated neurons from the arcuate nucleus of the rat. NPY
      analogues that activated all of the known NPY receptors (Y1-Y5), produced voltage
      dependent inhibition of Ca2+ currents and activation of inwardly rectifying K+
      currents in arcuate neurons. Both of these effects could occur simultaneously in
      the same cells. In some cells, activation of Y4 NPY receptors also caused
      oscillations in [Ca2+]i. NPY hyperpolarized arcuate neurons through the
      activation of a K+ conductance and increased the spike threshold. Molecular
      biological studies indicated that arcuate neurons possessed all of the previously
      cloned NPY receptor types (Y1, Y2, Y4, and Y5). Thus activation of multiple types
      NPY receptors on arcuate neurons can regulate both Ca2+ and K+ conductances
      leading to a reduction in neuronal excitability and a suppression of
      neurotransmitter release.

PMID- 10085365
TI  - Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of
      CA1 pyramidal neurons from hippocampal slices.
AB  - To investigate the physiological consequences of the increase in spine density
      induced by estradiol in pyramidal neurons of the hippocampus, we performed
      simultaneous whole cell recordings and Ca2+ imaging in CA1 neuron spines and
      dendrites in hippocampal slices. Four- to eight-days in vitro slice cultures were
      exposed to 17beta-estradiol (EST) for an additional 4- to 8-day period, and spine
      density was assessed by confocal microscopy of DiI-labeled CA1 pyramidal neurons.
      Spine density was doubled in both apical and basal dendrites of the CA1 region in
      EST-treated slices; consistently, a reduction in cell input resistance was
      observed in EST-treated CA1 neurons. Double immunofluorescence staining of
      presynaptic (synaptophysin) and postsynaptic (alpha-subunit of CaMKII) proteins
      showed an increase in synaptic density after EST treatment. The slopes of the
      input/output curves of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) and N-methyl-D-aspartate (NMDA) postsynaptic currents were steeper in
      EST-treated CA1 neurons, consistent with the observed increase in synapse
      density. To characterize NMDA-dependent synaptic currents and dendritic Ca2+
      transients during Schaffer collaterals stimulation, neurons were maintained at
      +40 mV in the presence of nimodipine, picrotoxin, and 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX). No differences in resting spine or dendritic Ca2+ levels were
      observed between control and EST-treated CA1 neurons. Intracellular Ca2+
      transients during afferent stimulation exhibited a faster slope and reached
      higher levels in spines than in adjacent dendrites. Peak Ca2+ levels were larger
      in both spines and dendrites of EST-treated CA1 neurons. Ca2+ gradients between
      spine heads and dendrites during afferent stimulation were also larger in EST
      treated neurons. Both spine and dendritic Ca2+ transients during afferent
      stimulation were reversibly blocked by D, L-2-amino-5-phosphonovaleric acid (D,L
      APV). The increase in spine density and the enhanced NMDA-dependent Ca2+ signals
      in spines and dendrites induced by EST may underlie a threshold reduction for
      induction of NMDA-dependent synaptic plasticity in the hippocampus.

PMID- 10085366
TI  - Action potentials in the dendrites of retinal ganglion cells.
AB  - The somas and dendrites of intact retinal ganglion cells were exposed by
      enzymatic removal of the overlying endfeet of the Muller glia. Simultaneous whole
      cell patch recordings were made from a ganglion cell's dendrite and the cell's
      soma. When a dendrite was stimulated with depolarizing current, impulses often
      propagated to the soma, where they appeared as a mixture of small depolarizations
      and action potentials. When the soma was stimulated, action potentials always
      propagated back through the dendrite. The site of initiation of action
      potentials, as judged by their timing, could be shifted between soma and dendrite
      by changing the site of stimulation. Applying QX-314 to the soma could eliminate
      somatic action potentials while leaving dendritic impulses intact. The absolute
      amplitudes of the dendritic action potentials varied somewhat at different
      distances from the soma, and it is not clear whether these variations are real or
      technical. Nonetheless, the qualitative experiments clearly suggest that the
      dendrites of retinal ganglion cells generate regenerative Na+ action potentials,
      at least in response to large direct depolarizations.

PMID- 10085367
TI  - Muscarinic receptors differentially modulate the persistent potassium current in
      striatal spiny projection neurons.
AB  - Cholinergic regulation of striatal spiny projection neuron activity is
      predominantly mediated through muscarinic receptor modulation of several
      subclasses of ion channels. Because of its critical role in governing the
      recurring episodes of hyperpolarization and depolarization characteristic of
      spiny neurons in vivo, the 4-aminopyridine-resistant, persistent potassium (K+)
      current, IKrp, would be a strategic target for modulation. The present results
      show that IKrp can be either suppressed or enhanced by muscarinic receptor
      stimulation. Biophysical analysis demonstrated that the depression of IKrp was
      associated with a hyperpolarizing shift in the voltage dependence of inactivation
      and a reduction in maximal conductance. By contrast, the enhancement of IKrp was
      linked to hyperpolarizing shifts in both activation and inactivation voltage
      dependencies. Viewed in the context of the natural activity of spiny neurons,
      muscarinic depression of IKrp should uniformly increase excitability in both
      hyperpolarized and depolarized states. In the hyperpolarized state, the reduction
      in maximal conductance should bolster the efficacy of impending excitatory input.
      Likewise, in the depolarized state, the decreased availability of IKrp produced
      by the shift in inactivation should enhance ongoing synaptic input. The
      alterations associated with enhancement of IKrp are predicted to have a more
      dynamic influence on spiny cell excitability. In the hyperpolarized state, the
      negative shift in activation should increase the flow of IKrp and attenuate
      subsequent excitatory synpatic input; whereas once the cell has traversed into
      the depolarized state, the negative shift in inactivation should reduce the
      availability of this current and diminish its influence on the existing
      excitatory barrage.

PMID- 10085368
TI  - Local excitatory circuits in the intermediate gray layer of the superior
      colliculus.
AB  - We have used photostimulation and whole cell patch-clamp recording techniques to
      examine local synaptic interactions in slices from the superior colliculus of the
      tree shrew. Uncaging glutamate 10-75 microm from the somata of neurons in the
      intermediate gray layer elicited a long-lasting inward current, due to direct
      activation of glutamate receptors on these neurons, and brief inward currents
      caused by activation of presynaptic neurons. The synaptic responses occurred as
      individual currents or as clusters that lasted up to several hundred
      milliseconds. Excitatory synaptic responses, which reversed at membrane
      potentials near 0 mV, could be evoked by uncaging glutamate anywhere within 75
      microm of an intermediate layer neuron. Our results indicate the presence of
      extensive local excitatory circuits in the intermediate layer of the superior
      colliculus and support the hypothesis that such intrinsic circuitry contributes
      to the development of presaccadic command bursts.

PMID- 10085369
TI  - Effect of hypertonicity on augmentation and potentiation and on corresponding
      quantal parameters of transmitter release.
AB  - Augmentation and (posttetanic) potentiation are two of the four components
      comprising the enhanced release of transmitter following repetitive nerve
      stimulation. To examine the quantal basis of these components under isotonic and
      hypertonic conditions, we recorded miniature endplate potentials (MEPPs) from
      isolated frog (Rana pipiens) cutaneous pectoris muscles, before and after
      repetitive nerve stimulation (40 s at 80 Hz). Continuous recordings were made in
      low Ca2+ high Mg2+ isotonic Ringer solution, in Ringer that was made hypertonic
      with 100 mM sucrose, and in wash solution. Estimates were obtained of m (no. of
      quanta released), n (no. of functional release sites), p (mean probability of
      release), and vars p (spatial variance in p), using a method that employed MEPP
      counts. Hypertonicity abolished augmentation without affecting potentiation.
      There were prolonged poststimulation increases in m, n, and p and a marked but
      transient increase in vars p in the hypertonic solution. All effects were
      completely reversed with wash. The time constants of decay for potentiation and
      for vars p were virtually identical. The results are consistent with the notion
      that augmentation is caused by Ca2+ influx through voltage-gated calcium channels
      and that potentiation is due to Na+-induced Ca2+ release from mitochondria. The
      results also demonstrate the utility of this approach for analyzing the dynamics
      of quantal transmitter release.

PMID- 10085370
TI  - Active signaling of leg loading and unloading in the cockroach.
AB  - The ability to detect changes in load is important for effective use of a leg in
      posture and locomotion. While a number of limb receptors have been shown to
      encode increases in load, few afferents have been demonstrated to signal leg
      unloading, which occurs cyclically during walking and is indicative of slipping
      or perturbations. We applied mechanical forces to the cockroach leg at controlled
      rates and recorded activities of the tibial group of campaniform sensilla,
      mechanoreceptors that encode forces through the strains they produce in the
      exoskeleton. Discrete responses were elicited from the group to decreasing as
      well as increasing levels of leg loading. Discharges of individual afferents
      depended on the direction of force application, and unit responses were
      correlated morphologically with the orientation of the receptor's cuticular cap.
      No units responded bidirectionally. Although discharges to decreasing levels of
      load were phasic, we found that these bursts could effectively encode the rate of
      force decreases. These discharges may be important in indicating leg unloading in
      the step cycle during walking and could rapidly signal force decreases during
      perturbations or loss of ground support.

PMID- 10085371
TI  - Single cortical neurons serve both echolocation and passive sound localization.
AB  - The pallid bat uses passive listening at low frequencies to detect and locate
      terrestrial prey and reserves its high-frequency echolocation for general
      orientation. While hunting, this bat must attend to both streams of information.
      These streams are processed through two parallel, functionally specialized
      pathways that are segregated at the level of the inferior colliculus. This report
      describes functionally bimodal neurons in auditory cortex that receive converging
      input from these two pathways. Each brain stem pathway imposes its own suite of
      response properties on these cortical neurons. Consequently, the neurons are
      bimodally tuned to low and high frequencies, and respond selectively to both
      noise transients used in prey detection, and downward frequency modulation (FM)
      sweeps used in echolocation. A novel finding is that the monaural and binaural
      response properties of these neurons can change as a function of the sound
      presented. The majority of neurons appeared binaurally inhibited when presented
      with noise but monaural or binaurally facilitated when presented with the
      echolocation pulse. Consequently, their spatial sensitivity will change,
      depending on whether the bat is engaged in echolocation or passive listening.
      These results demonstrate that the response properties of single cortical neurons
      can change with behavioral context and suggest that they are capable of
      supporting more than one behavior.

PMID- 10085372
TI  - Microstimulation of the lateral wall of the intraparietal sulcus compared with
      the frontal eye field during oculomotor tasks.
AB  - We compared the effects of intracortical microstimulation (ICMS) of the lateral
      wall of the intraparietal sulcus (LIP) with those of ICMS of the frontal eye
      field (FEF) on monkeys performing oculomotor tasks. When ICMS was applied during
      a task that involved fixation, contraversive saccades evoked in the LIP and FEF
      appeared similar. When ICMS was applied to the FEF at the onset of voluntary
      saccades, the evoked saccades collided with the ongoing voluntary saccade so that
      the trajectory of voluntary saccade was compensated by the stimulus. Thus the
      resultant saccade was redirected and came close to the endpoint of saccades
      evoked from the fixation point before the start of voluntary saccade. In
      contrast, when ICMS was applied to the LIP at the onset of voluntary saccades,
      the resultant saccade followed a trajectory that was different from that evoked
      from the FEF. In that case, the colliding saccades were redirected toward an
      endpoint that was close to the endpoint of saccades evoked when animals were
      already fixating at the target of the voluntary saccade. This finding suggests
      that the colliding saccade was directed toward an endpoint calculated with
      reference to the target of the voluntary saccade. We hypothesize that, shortly
      before initiation of voluntary saccades, a dynamic process occurs in the LIP so
      that the reference point for calculating the saccade target shifts from the
      fixation point to the target of a voluntary saccade. Such predictive updating of
      reference points seems useful for immediate reprogramming of upcoming saccades
      that can occur in rapid succession.

PMID- 10085373
TI  - Intracellular Ca2+ concentrations in cultured chicken photoreceptor cells:
      sustained elevation in depolarized cells and the role of dihydropyridine
      sensitive Ca2+ channels.
AB  - PURPOSE: Retinal photoreceptor cells are tonically depolarized in darkness. Ca2+
      influx in darkness plays a critical role in the regulation of neurotransmitter
      release and melatonin synthesis in these sensory cells. The purpose of the
      present study was to examine the dynamic changes of intracellular Ca2+
      concentrations ([Ca2+]in ) in response to a tonic depolarizing stimulus and to
      determine the role of dihydropyridine-sensitive calcium channels in the response.
      METHODS: Photoreceptor cells were prepared from embryonic chick retina and
      cultured for 6-12 days. Cells were depolarized by exposure to 35 mM extracellular
      K+. [Ca2+]in of individual photoreceptor cell bodies/synaptic terminals was
      determined by ratiometric fura-2 image analysis. RESULTS: Chemical depolarization
      with 35 mM [K+]out greatly increased [Ca2+]in of inner segment/synaptic terminal
      regions of photoreceptors. The increase usually reached a plateau after the first
      few minutes of stimulation and was sustained for prolonged periods (>2 h) in the
      presence of high K+. When the extracellular K+ concentration was reduced, the
      [Ca2+]in rapidly returned to the basal level. Substitution of 1 mM CoCl2 for
      CaCl2 in the superfusion medium rapidly and reversibly reduced the [Ca2+]in of
      depolarized photoreceptor cells. Antagonists of L-type Ca2+ channels,
      nitrendipine and nifedipine, inhibited the K+-evoked increase of [Ca2+]in. Bay K
      8644, a dihydropyridine Ca2+ channel agonist, potentiated the increase of
      [Ca2+]in elicited by high K+. In some cells, Bay K 8644 alone increased [Ca2+]in
      under basal conditions. CONCLUSIONS: The increase of [Ca2+]in elicited by
      depolarization with 35 mM extracellular K+ is due to influx of calcium through
      the dihydropyridine-sensitive voltage-gated channels. Intracellular [Ca2+]
      remains elevated for extended periods of time during tonic depolarization. This
      sustained response requires continuous Ca2+ channel activity.

PMID- 10085374
TI  - Deamidation of alpha-A crystallin from nuclei of cataractous and normal human
      lenses.
AB  - PURPOSE: To quantitate the extent of deamidation of asparagine-101, glutamine-50,
      and glutamine-6 of alpha-A crystallin in the nucleus from human cataractous and
      normal lenses. METHODS: Reverse phase chromatography was used to prepare alpha-A
      crystallin from total proteins of the nucleus from cataractous and age-matched
      normal human lenses. Synthetic peptides were made corresponding to the expected
      amidated and deamidated tryptic fragments containing asparagine-101, glutamine
      50, and glutamine-6. The peptides were used to identify and quantitate amidated
      and deamidated forms of tryptic fragments from alpha-A crystallin eluting from a
      reverse phase column. RESULTS: Significant amounts of deamidation of asparagine
      101 and glutamine-50, but not glutamine-6, were present in alpha-A crystallin
      from nuclear sections of both cataractous and age-matched normal lenses.
      Quantitative analysis of tryptic peptides containing these residues indicated no
      statistical difference in deamidation in cataractous versus normal lenses.
      CONCLUSIONS: There was no significant difference in the extent of deamidation of
      asparagine-101, glutamine-50, and glutamine-6 for alpha-A crystallin, purified
      from the nucleus of cataractous versus age-matched normal lenses. These results
      strongly suggest that deamidation of these residues does not play a role in the
      biogenesis of human nuclear cataract.

PMID- 10085375
TI  - FORUM: Land Degradation Problems and Their Implications for Food Shortage in
      South Wello, Ethiopia.
AB  - / Understanding the problems of land degradation and seeking long-lasting
      solutions to these problems should be one of the central concerns of countries
      such as Ethiopia where agriculture is the mainstay of no less than 85% of the
      population. To this end, the collaboration of policy makers, researchers, donor
      agencies, and the local people is indispensable. In this paper an attempt is made
      to discuss the causes of land degradation and the reasons for the failure in the
      endeavors made to solve the problems. Possible solutions, which may help to
      ameliorate the situation, are also suggested. The study deals with South Wello (a
      region in northern Ethiopia), but the assessment is, by and large, a reflection
      of most of the highlands in the country. KEY WORDS: Agroforestry; Donor agencies;
      Food for work; Hillside closures; Land rehabilitation; Local participation;
      Population growth; Reforestation

PMID- 10085376
TI  - Environmental Management and the New Politics of Western Water: The Animas-La
      Plata Project and Implementation of the Endangered Species Act.
AB  - / This paper explores the new politics of western water policy through an
      examination of the Animas-La Plata water project and implementation of the
      Endangered Species Act. It is suggested that the focus of western water
      programming has shifted from the source of distributed funds, the United States
      Congress, to the agencies originally created to deliver federal benefits because
      funding for new project construction has not been forthcoming. Under this new
      system, members of Congress continue to excite their constituents with promises
      of money for new project starts, while the administrative agencies perform the
      myriad duties needed to keep these projects alive. The result is that political
      objectives have replaced operational/management objectives in administrative
      processes. In this case, the author demonstrates how resource managers in the
      Bureau of Reclamation manipulated hydrological analysis to control administrative
      process, why their manipulation was unfair, and perhaps illegal, and why
      biologists from the US Fish and Wildlife Service accepted the analysis. While
      ostensibly protecting all interests, the result is that none of the objectives of
      federal water programming are achieved. KEY WORDS: Environmental management;
      Administrative politics; Water policy; Endangered Species Act; Animas-La Plata,
      Bureau of Reclamation

PMID- 10085377
TI  - PROFILE: Management of Sedimentation in Tropical Watersheds.
AB  - / The sedimentation of reservoirs is a serious problem throughout the tropics,
      yet most attempts to control sedimentation in large river basins have not been
      very successful. Reliable information on erosion rates and sources of sediments
      has been lacking. In regions where geologically unstable terrain combines with
      high rainfall, natural erosion rates might be so high that the effects of human
      activity are limited. Estimates of natural erosion in these situations often have
      been poor because of the episodic nature of most erosion during large storms and
      because mass-wasting may supply much of the sediment. The predominance of mass
      wasting in some watersheds can result in an unexpectedly high ratio of bedload to
      suspended load, shifting sedimentation to "live" rather than "dead" storage
      within reservoirs. Furthermore, the inappropriate use of the Universal Soil Loss
      Equation to assess the effectiveness of erosion control measures has led to
      inaccurate estimates of the sediment reduction benefits that could accrue to
      watershed treatment efforts. Although reducing erosion from cultivated areas is
      desirable for other reasons, efforts aimed at reducing reservoir sedimentation by
      controlling agricultural sources of erosion may have limited benefits if the
      principal sources are of natural origin or are associated with construction of
      the dams and reservoirs and with rural roads and trails. Finally, the most
      appropriate locations for watershed rehabilitation depend on the magnitude of
      temporary storage of colluvium and alluvium within the river basin: Where storage
      volume is large and residence time of sediment very long, reducing agricultural
      erosion may have limited impacts on sedimentation within the expected life of a
      reservoir. Systematic development and analysis of sediment budgets for
      representative watersheds is needed to address these limitations and thereby
      improve both the planning of river basin development schemes and the allocation
      of resources towards reducing sedimentation. When sedimentation of reservoirs is
      the key issue, sediment budgets must focus especially on channel transport rates
      and sediment delivery from hillsides. Sediment budgets are especially critical
      for tropical areas where project funds and technical help are limited. Once
      sediment budgets are available, watershed managers will be able to direct erosion
      control programs towards locations where they will be most effective. KEY WORDS:
      Tropical watersheds; Sedimentation; Reservoirs; Erosion control

PMID- 10085378
TI  - Understanding Dispute Resolution Processes for American and Australian Public
      Wildlands: Towards a Conceptual Framework for Managers.
AB  - / The last 20 years have seen the successful application of environmental dispute
      resolution processes, where people voluntarily negotiate toward mutually
      acceptable solutions, to many environmental disputes. The effects of contextual
      influences, such as the number of parties and presence of deadlines, on outcomes
      are known and frequently described. Less well documented and understood are the
      interaction processes themselves. This paper draws on two case studies to develop
      a conceptual framework describing these processes. Disputes associated with
      management planning for the Bob Marshall Wilderness Complex in the United States
      and Fitzgerald River National Park in Australia provided the cases. The
      conceptual framework derived had eight sequential stages: (1) joint definition of
      problems, (2) uncertainty about what to do, (3) agreement on group procedures,
      (4) realization of interdependence, (5) enthusiasm about collective
      possibilities, (6) commitment to working together, (7) consolidation of the
      group, and (8) implementation of a resolution. The framework provides new
      insights for managers of public wildlands, especially the need for varying but
      ongoing managerial involvement in dispute resolution processes. High levels of
      involvement and influence are essential at the beginning in problem definition
      and group procedure design and at the end in implementing resolutions.
      Conversely, agency members must be willing to exert less influence, while still
      being involved and committed to collective purposes, during the middle stages.
      Also apparent from the conceptual framework is the importance of developing
      shared understandings and of allowing sufficient time for understanding to
      develop, if successful resolution is to be achieved. KEY WORDS: Environmental
      dispute resolution; Conceptual framework; Public wildlands; Shared
      understandings; Australia

PMID- 10085379
TI  - Guidelines and Techniques for Improving the NEPA Process.
AB  - / The Council on Environmental Quality's (CEQ's) principal aims in implementing
      the National Environmental Policy Act (NEPA) are (1) to reduce paperwork, (2) to
      avoid delay, and most importantly (3) to produce better decisions that protect,
      restore, and enhance the environment. This paper presents four strategies for
      improving the NEPA process along with tools that can be used to implement each
      strategy. The tools include guidelines for project management and problem
      definition, tips for acquiring existing information and identifying issues of
      public concern, worksheets on how to identify and analyze potential impacts on
      resources, ideas for enhancing NEPA documents, and a NEPA process checklist. The
      tools can be used at various stages of the NEPA process and provide a toolbox of
      guidelines and techniques to improve implementation of the NEPA process by
      focusing the pertinent information for decisionmakers and stakeholders. KEY
      WORDS: National Environmental Policy Act; NEPA; Environmental impact assessment;
      Ecosystem management

PMID- 10085380
TI  - Key Elements of Landscape Pattern Measures.
AB  - / Describing patterns in the landscape and interpreting the effects of these
      patterns on flora, fauna, and other factors has been of long-standing interest.
      Many descriptors have been developed, and these aggregate factors into a single
      index. The identical numerical result for a multifactor index can be attained by
      using an array of very different values. We list six important factors for
      describing a mapped area: the area, the classes, proportion of dominant class,
      number of polygons, polygon size variance, and elevation range and suggest that
      these and their map statistics will encompass most of the observed phenomena
      associated with things perceived as land pattern. KEY WORDS: Landscape ecology;
      Diversity; Spatial analyses; Forest; Indices

PMID- 10085381
TI  - RESEARCH: Environmental Priority-Setting Through Comparative Risk Assessment.
AB  - / More than three dozen states and communities in the United States have
      undertaken comparative risk projects to establish environmental priorities and,
      thus, to address their most important environmental problems. This trend has been
      supported by a growing consensus among subnational governments that they are
      increasingly encumbered with prescriptive, top-down environmental regulations and
      policies without regard to the policies' efficacy, benefit, or cost. Despite the
      rising use of comparative risk projects, few studies have systematically analyzed
      and compared them. The purpose of our research was to fill this void. Weexamined
      key elements of comparative risk projects including how they were administered;
      how they involved the public; how they characterized, ranked, and prioritized
      risks; whether and how they implemented ranking results; and whether and how they
      evaluated project results. The research team reviewed project reports and
      independent studies and undertook a survey of risk project participants. Results
      showed that while many priority-setting projects have successfully identified
      environmental problems and characterized and ranked their risks, few have
      developed risk-management strategies. Successes to date include increasing
      environmental awareness among participants; building consensus and establishing
      collaboration among diverse stakeholders; and establishing novel means of public
      involvement. However, no project that we evaluated has, as yet, documented
      achievement of a system for developing and implementing environmental priorities
      in order to mitigate their most significant environmental problems. Further, it
      may be difficult to know if and when this objective is met unless projects
      establish mechanisms for evaluating their results, a project element that was
      often missing or limited in scope. We also discuss the challenges to developing
      implementable risk-management strategies and conclude by citing future research
      needs. KEY WORDS: Comparative risk assessment; Environmental priorities; Risk
      ranking

PMID- 10085382
TI  - What Is Source Reduction? A Critique and Comparative Analysis of Polish and
      American Students.
AB  - / Source reduction is recognized as the preferred form of waste management, but
      its definition is ambiguous. This study proposes four underlying dimensions of
      the source reduction concept. Source reduction is foremost a preventive activity
      that reduces the number or extent of environmental impacts. Second, source
      reduction can prevent both resource consumption and pollution generation impacts.
      Third, source reduction may be viewed as both a producer and consumer activity.
      Lastly, it may include frugal and more efficient activities. In surveys exploring
      these fourdimensions, Polish and American university students evaluated whether
      20 activities were examples of source reduction. The American students gave
      higher ratings to preventive activities over adaptive activities. The Polish
      students most prominently rated efficient over frugal activities. Factor analysis
      indicated that both samples identified a group of consumer-based resource
      conservation activities, with the American students recognizing a cluster of
      recycling activities. In a separate ranking of environmental protection
      priorities, the Polish students endorsed pollution prevention, whereas the
      American students favored both efficient and frugal resource conservation. These
      findings suggest that the conceptualization of source reduction varies according
      to contextual factors and that prevention is still an obscure environmental
      management theme. KEY WORDS: Source reduction; Pollution prevention; Resource
      conservation; Frugality; Poland

PMID- 10085383
TI  - Water Level Effects on Growth of Melaleuca Seedlings from Lake Okeechobee
      (Florida, USA) Littoral Zone.
AB  - / The invasive exotic wetland tree, Melaleuca quinquenervia, is expanding rapidly
      throughout seasonally wet areas of southern Florida (USA), including the littoral
      zone of Lake Okeechobee. Natural resource managers are concerned that a lower
      lake level regulation schedule under consideration for Lake Okeechobee, while
      potentially beneficial to overall ecosystem health, might increase the rate of
      Melaleuca expansion. To investigate this possibility, Melaleuca saplings
      (harvested from the littoral zone) and 7-week-old seedlings (grown from harvested
      seeds) were subjected to various hydroperiod treatments in replicated mesocosms.
      Hydroperiod treatments were selected based on a simulation of historical water
      level variations. Saplings grew taller under longer hydroperiods with fluctuating
      water levels, including periods of submersion. Time since germination affected
      the response of seedlings to inundation. Submersed 7-week-old seedlings grew
      slower and had less biomass than submersed 12-week-old seedlings, yet mortality
      was low at both ages. Melaleuca's plasticity allows it to adapt to hypoxic,
      aquatic conditions by means of aquatic heterophylly and adventitious roots. Algae
      and drought also increased mortality. Based on faster growth of Melaleuca under
      longer hydroperiods and its adaptability to seasonal flooding, a lower lake
      regulation schedule may not stimulate its expansion. Therefore, water levels
      should not be manipulated only to control Melaleuca. Control of Melaleuca should
      continue using current practices such as manual removal or chemical treatment.
      KEY WORDS: Melaleuca; Lake Okeechobee; Littoral zone; Water level; Regulation
      schedule

PMID- 10085384
TI  - A Conceptual Model for Defining and Assessing Condition of Forest Stands.
AB  - / Determining what indicators can be used to measure forest health has been much
      discussed but largely unresolved in the forestry literature. A model is presented
      in which the condition of a stand is quantified relative to a suitable target
      condition based on a preselected set of stands that, in the opinions of the
      managers, meet management objectives. Each stand was characterized by a list of
      variables that were selected from the existing forest database. We termed these
      characterizations stand profiles. Profiles of inventory data for 28 stands, each
      managed for either wildlife habitat or timber production in the Wallowa-Whitman
      National Forest in eastern Oregon, USA, were used to develop this model. Healthy
      stands were represented by points in multidimensional scaling space that fell
      within the bounds of a 65% kernel density estimation of the distribution of
      stands preselected for each management objective. Stands falling outside these
      bounds were, by definition unhealthy, and the distance from the bounds is a
      measure of degree of unhealthiness. Operationally, the objectives of
      silvicultural manipulations would be to maintain or move points to within the
      target space by selectively manipulating the values composing stand profiles. The
      direction and length of the trajectory associated with manipulations is an
      indicator of the effect of management actions. More work needs to be done to
      develop and validate this method. KEY WORDS: Monitoring forest condition; Forest
      health; Decision making; Silviculture prescriptions; Forest management; Forest
      pests; Forest diseases; Forest insects

PMID- 10085385
TI  - Temperature, Salinity, and Fluorescence in Southern North Sea: High-Resolution
      Data Sampled from a Ferry.
AB  - / In 1991 and 1992, temperature, salinity, and fluorescence were measured by
      automatic continuous registration using instrumentation on a ferry crossing the
      southern North Sea daily along a transect between Zeebrugge, Belgium, and Hull,
      United Kingdom. The temperature ranged between 4 and 21 degrees C off the Belgian
      coast and between 6 and 17 degrees C in the middle of the transect. Salinity
      varied between 34 and 35.5 PSU in the offshore part of the transect, but showed
      much larger variation along the Belgian and UK estuarine coasts. Fluorescence,
      which was used as a measure of phytoplankton biomass, was highest at the
      continental coast and lowest near the English coast. Spring blooms of
      phytoplankton were found along the continental coast and in the channel
      influenced water; in 1991 the blooms were denser than in 1992. Some summer blooms
      were also recorded. Water masses could be distinguished on the basis of salinity
      and fluorescence patterns. The general patterns in the data are compared with the
      literature and discussed in relation to river discharge, light penetration, and
      wind speed and direction. Finally, the value of automatic and frequent
      measurements of fluorescence for monitoring phytoplankton is compared with less
      frequent observations at selected stations. It is concluded that accurate
      information about phytoplankton biomass can only be established from the high
      frequency data. KEY WORDS: Monitoring; Sampling; North Sea; Ferry; Fluorescence;
      Salinity; Temperature

PMID- 10085386
TI  - Relationships Between Landscape Characteristics and Nonpoint Source Pollution
      Inputs to Coastal Estuaries.
AB  - / Land-use activities affect water quality by altering sediment, chemical loads,
      and watershed hydrology. Some land uses may contribute to the maintenance of
      water quality due to a biogeochemical transformation process. These land-use/land
      cover types can serve as nutrient detention zones or as nutrient transformation
      zones as dissolved or suspended nutrients or sediments move downstream. Despite
      research on the effects of individual land-use/land-cover types, very little has
      been done to analyze the joint contributions of multiple land-use activities.
      This paper examines a methodology to assess the relationships between land-use
      complex and nitrate and sediment concentrations [nonpoint source (NPS)
      pollutants] in streams. In this process, selected basins of the Fish River,
      Alabama, USA, were delineated, land-use/land-cover types were classified, and
      contributing zones were identified using geographic information system (GIS) and
      remote sensing (RS) analysis tools. Water samples collected from these basins
      were analyzed for selected chemical and physical properties. Based on the
      contributions of the NPS pollutants, a linkage model was developed. This linkage
      model relates land use/land cover with the pollution levels in the stream.
      Linkage models were constructed and evaluated at three different scales: (1) the
      basin scale; (2) the contributing-zone scale; and (3) the stream-buffer/riparian
      zone scale. The contributing-zones linkage model suggests that forests act as a
      transformation zone, and as the proportion of forest inside a contributing zone
      increases (or agricultural land decreases), nitrate levels downstream will
      decrease. Residential/urban/built-up areas were identified as the strongest
      contributors of nitrate in the contributing-zones model and active agriculture
      was identified as the second largest contributor. The regression results for the
      streambank land-use/land-cover model (stream-buffer/riparian-zone scale) suggest
      that water quality is highest when passive land uses, such as forests and
      grasslands, are located adjacent to streams. Nonpassive land uses (agricultural
      lands or urban/built-up areas) located adjacent to streams have negative impacts
      on water quality. The model can help in examining the relative sensitivity of
      water-quality variables to alterations in land use made at varying distances from
      the stream channel. The model also shows the importance of streamside management
      zones, which are key to maintenance of stream water quality. The linkage model
      can be considered a first step in the integration of GIS and ecological models.
      The model can then be used by local and regional land managers in the formulation
      of plans for watershed-level management. KEY WORDS: Water quality; Land-use
      complex; Geographic information system; Nonpoint source pollution; Forested
      buffers

PMID- 10085387
TI  - ENVIRONMENTAL AUDITING: Integrating Environmental Characteristics and Fisheries
      Management in Northern Finland River Impoundments.
AB  - / Three large rivers in northern Finland, the Kemijoki, Iijoki, and Oulujoki
      rivers, were dammed for hydropower generation in the 1940s-1960s. Due to
      differences in environmental conditions, these impoundments require detailed
      study to produce guidelines for fisheries management.Water quality, hydrology,
      vegetation, and geomorphology data of 16 impoundments were gathered. Shoreline
      land-use data were derived from maps, and fish assemblage data were collected by
      exploratory fishing and from the annual fishery statistics. The relations among
      environmental variables were studied, and a classification of the impoundments
      was developed by hierarchical cluster analysis. Consequently, three impoundment
      groups with different environmental characteristics were formed. Significant
      differences among impoundment groups were also detected in fish yield. We
      conclude that the variation in environmental conditions, together with
      differences in fish communities in the impoundments were important enough to
      justify the claim that impoundments of different types require different
      management strategies. KEY WORDS: Impoundments; River regulation; Fish
      assemblage; Water quality; Aquatic vegetation; Finland

PMID- 10085388
TI  - Antibiotic administration in patients undergoing common surgical procedures in a
      community teaching hospital: the chaos continues.
AB  - The influence of recently published guidelines by the Surgical Infection Society
      (SIS) on current surgical practice are not well documented. The appropriateness
      of antibiotic administration in a cohort of surgical patients undergoing elective
      and emergency surgery in a department of surgery in an urban, community-based,
      private, 560-bed teaching hospital was retrospectively reviewed. The following
      were the criteria defining administration as appropriate as modified from SIS
      guidelines: Prophylactic use: (1) started prior to operation; (2) spectrum
      appropriate to the specific operation; (3) duration </= 24 hours. Therapeutic
      use: (1) started prior to operation; (2) spectrum appropriate to pathology; (3)
      Duration </= 24 hours for contamination or "resectable" infection and </= 5 days
      for established infection in the absence of clinical evidence of persisting
      infection. Any switchover from an appropriate agent to another appropriate or
      inappropriate agent in the same patient in the absence of microbiologic or
      clinical indication was considered inappropriate administration. We reviewed the
      charts of 211 randomly selected patients who underwent elective (n = 132) or
      emergency (n = 79) procedures during 1996. The operations included gastrectomy (n
      = 22), appendectomy (n = 27), open (n = 5) or laparoscopic (n = 27)
      cholecystectomy, colectomy (n = 28), hysterectomy (n = 8), laparotomy for
      intestinal obstruction (n = 11), mastectomy (n = 26), and ventral hernia repair
      (n = 37). A total of 17 antibiotics were used for prophylaxis and 21 for therapy.
      In 156 patients (74%) the administration was considered inappropriate. Eight
      patients in the inappropriate group developed diarrhea (two cases of Clostridium
      difficile-induced colitis) compared to two cases of diarrhea in the appropriate
      group (nonsignificant). The average duration of administration after elective and
      emergency operations was 3.3 and 5. 7 days, respectively. The total expense for
      excessive duration of administration was $18,533. Many surgeons are not familiar
      with the spectrum of antimicrobials and often do not distinguish between
      prophylactic and therapeutic administration. Antibiotic usage in current surgical
      practice is often inappropriate, excessive, and chaotic.

PMID- 10085389
TI  - Management of nonpalpable, mammographically detectable breast lesions.
AB  - A series of 151 women underwent 156 preoperative localizations of nonpalpable,
      mammographically detected breast lesions. Indications for biopsy were (1) a
      cluster of more than five fine microcalcifications; (2) a solid lump found by
      ultrasound investigation; and (3) a radiologic abnormality of the breast
      parenchyma. The lesions were localized preoperatively using the hook-wire method
      (Frank needle), and all biopsies were performed under general anesthesia.
      Carcinoma was discovered in 34 (21.8%) cases; in 22 (64.7%) it was a noninvasive
      cancer (9 with microinvasions) and in 12 (35.3%) an invasive carcinoma with a
      mean tumor diameter of 0.8 cm. The highest malignancy rate was found among those
      with microcalcifications (21 of 81 cancers, or 25.9%). Lymph node involvement was
      seen in 25% of patients with invasive carcinomas. In conclusion, the needle
      localization of nonpalpable breast lesions is a simple, accurate method for early
      detection of small cancers with favorable prognosis.

PMID- 10085390
TI  - Expression of pepsinogen C in gynecomastias and male breast carcinomas.
AB  - Pepsinogen C is a proteolytic enzyme involved in the digestion of proteins in the
      stomach; it is also synthesized by a significant percentage of female breast
      carcinomas. In addition, it has been demonstrated that pepsinogen C is one of the
      few proteins induced by androgens in breast carcinoma cells. Here we evaluate the
      expression of pepsinogen C by immunoperoxidase staining in normal breast tissue
      from 3 male patients, 15 gynecomastia tissues, 2 male in situ breast carcinomas,
      and 68 male invasive breast carcinomas. Pepsinogen C immunostaining values were
      quantified in male breast tumors using the HSCORE system, which considers both
      the intensity and the percentage of cells staining at each intensity. The results
      indicated positive immunohistochemical staining for pepsinogen C in all
      gynecomastia tissues, the two in situ ductal carcinomas, and 52 of 68 invasive
      breast carcinomas (76.4%). The three normal breast tissues analyzed showed
      negative staining for pepsinogen C, whereas invasive tumors showed clear
      differences among them with regard to the intensity and percentage of staining
      cells. In addition, pepsinogen C scores were significantly higher in well
      differentiated (grade I, 188.7) and moderately differentiated (grade II, 145.8)
      tumors than in poorly differentiated (grade III, 98.5) tumors (p = 0. 032).
      Similarly, significant differences in pepsinogen C content were found between
      estrogen receptor (ER)-positive tumors and ER-negative tumors (158.5 vs. 44.3,
      respectively; p = 0.009). Patients with pepsinogen C-positive tumors reached
      longer relapse-free and overall survival periods than did those with tumors with
      negative staining, but no statistical differences were observed between survival
      curves calculated for these two groups of patients. This results demonstrate
      expression of pepsinogen C by gynecomastias and by a high percentage of male
      breast carcinomas and may indicate an important role of pepsinogen C in the
      pathophysiology of male breast diseases.

PMID- 10085391
TI  - Regeneration of abdominal wall aponeurosis: new dimension in Marlex peritoneal
      sandwich repair of incisional hernia.
AB  - Loss of abdominal wall substance is a major cause of incisional hernia formation.
      It makes repair of this iatrogenic human ailment a difficult surgical problem.
      The abdominal wall substance loss has compelled the world's surgical community
      dealing with this condition to substantiate the repair with extra material such
      as skin, fascia, wire mesh, and lately biocompatible synthetic mesh. Even though
      the synthetic mesh is compatible and well tolerated by body tissues, it is not
      without complications. Regenerative repair in the region of the abdominal wall
      with substance loss is probably the best repair if it can be achieved. With
      reasonable success in animal experiments and the positive regenerative capacity
      of stem cells to transform the peritoneum into an aponeurotic layer, the new
      technique using a Marlex peritoneal sandwich for repair of large incisional
      hernias was attempted but was not reported in the article published in the World
      Journal of Surgery in 1991. The present study is based on experiments on seven
      mongrel dogs. A suitable embryonal segment of autogenous peritoneum was excised
      and transferred to the rectus sheath region. The gross appearance of the grafted
      membrane 3 months after operation revealed tough, thick tissue formation. The
      histology confirmed the presence of collagen fiber tissue in layers similar to
      the aponeurosis in the grafted peritoneal membrane. The use of this regeneration
      in the Marlex peritoneal sandwich technique of repair of large incisional hernias
      and the scientific rationale of tissue regeneration by desired metaplasia is
      discussed.

PMID- 10085392
TI  - Muscle force and bone mineral density after parathyroidectomy and subcutaneous
      autotransplantation for secondary hyperparathyroidism.
AB  - The object of this study was to determine the muscle force and bone mineral
      density (BMD) of patients with secondary hyperparathyroidism before and 3 months
      after operation. Thirty-nine patients with secondary hyperparathyroidism and
      regular dialysis were operated. Their ages were 47 +/- 12 (mean +/- SD) years and
      duration of dialysis was 70.5 +/- 35.8 months. The clinical symptoms included
      bone pain in 23 patients (59%), skin itching in 21 (53.8%), general weakness in
      13 (33.3%), conscious disturbance in 2, chest tightness in 1, and failure to
      thrive in 1. Total parathyroidectomy and autotransplantation of 60 mg of
      parathyroid gland into subcutaneous tissue was done routinely. BMD was measured
      in the lumbar spine (L2-L4) and left proximal femur, expressed as grams per
      square centimeter and as fracture risk. The extension force of the quadriceps
      muscle was measured at 60 degrees of right knee flexion, expressed as newtons (N)
      in a peak force and an average force. Three months after operation the BMD of the
      study group increased (in g/cm2) from 1.063 +/- 0.181 to 1.148 +/- 0.149 (p <
      0.001) in L2-4 (n = 25), from 0.792 +/- 0.14 to 0.875 +/- 0.161 (p < 0.001), in
      femoral neck (n = 25), from 0.672 +/- 0.171 to 0.754 +/- 0.21 (p < 0. 001) in
      Ward's triangle (n = 25), and from 0.69 +/- 0.149 to 0.738 +/- 0.143 (p < 0.001)
      in trochanter (n = 25). Fracture risk also was reduced significantly 3 months
      after operation at L2-4 (p = 0.003), femoral neck (p = 0.001), Ward's triangle
      (p= 0.003), and trochanter (p = 0.005). Muscle force (in newtons) increased from
      264.8 +/- 110. 5 to 326 +/- 110.9 (p = 0.023) in peak force (n = 18) and from
      195.3 +/- 90.4 to 258 +/- 99 (p = 0.012) in average force (n = 18). The patients
      with general weakness had improved muscle force more prominently than those
      without general weakness. In addition to skin itching, bone pain, and soft tissue
      calcification, general weakness that causes disability is an indication for
      surgery in secondary hyperparathyroidism. After parathyroidectomy and
      autotransplantation, the muscle force tends to increase, especially in those with
      general weakness. An increment of BMD and reduction of fracture risk are also
      found after surgery.

PMID- 10085393
TI  - Increased rate of cholecystectomy after introduction of laparoscopic
      cholecystectomy in Saudi Arabia.
AB  - A rapid increase in the rate of cholecystectomy was reported in eastern Saudi
      Arabia between 1977 and 1986. The aim of this study was to determine whether the
      rate of cholecystectomy in the same region was still rising after the
      introduction of laparoscopic cholecystectomy. From 1987 to 1995 a total of 24
      hospitals in eastern Saudi Arabia were surveyed using a questionnaire. During the
      9-year study period, the rate of total cholecystectomy (open and laparoscopic)
      increased by 91%. Whereas the cholecystectomy rate decreased by 4% per annum from
      1987 to 1990, it increased by 63.7% from 1991 to 1995 after the introduction of
      laparoscopic cholecystectomy. The increase in the rates of cholecystectomy was
      observed in all age groups and both sexes. Cholecystectomy was, however, most
      frequent among the age group 45-64 years followed by the age group 25-44 years.
      Young and female patients were more likely to undergo laparoscopic
      cholecystectomy than the open procedure. The rise in cholecystectomy rate
      deserves further evaluation with regard to the following: reasons for the
      increased rate of cholecystectomy, cholecystectomy-related morbidity and
      mortality, and the total costs of cholecystectomy.

PMID- 10085394
TI  - Prospective evaluation of selective defunctioning stoma for low anterior
      resection with total mesorectal excision.
AB  - Low anterior resection with total mesorectal excision for rectal carcinoma is
      associated with a high anastomotic leakage rate, and the effectiveness of a
      defunctioning stoma in preventing anastomotic leakage remains controversial. In
      this study a policy of selective defunctioning stoma for stapled colorectal
      anastomosis after low anterior resection with total mesorectal excision in 148
      consecutive patients was evaluated prospectively. A defunctioning stoma was
      performed in 61 patients (41%) considered at high risk of anastomotic leakage.
      Clinical leakage occurred in 2 patients (3.3%) with a stoma and 11 patients
      (12.6%) without a stoma (p = 0.047). Among those without a stoma, the leakage
      rate among male patients (20.9%) was significantly higher than that for female
      patients (4. 5%) (p = 0.022). Leakage subsided with conservative treatment in the
      two patients with a stoma, but seven patients without a stoma developed
      peritonitis requiring laparotomy. No deaths resulted from leakage, and there was
      one hospital death (0.6%) in the whole group. Median hospital stay was similar
      with and without a stoma (13.0 vs. 12.0 days) (p = 0.290). Closure of the stoma
      was associated with no mortality, a morbidity rate of 8.7%, and a median hospital
      stay of 6. 0 days. In conclusion, a defunctioning stoma is effective in
      preventing clinical anastomotic leakage after low anterior resection with total
      mesorectal excision. The relatively high incidence of leakage in the low risk
      group indicates the difficulty of predicting anastomotic leakage and hence the
      need for more liberal use of a defunctioning stoma especially in male patients.

PMID- 10085395
TI  - Intraabdominal nonvascular operations combined with abdominal aortic aneurysm
      repair.
AB  - The therapeutic approach to a patient who has an abdominal aortic aneurysm (AAA)
      and an intraabdominal nonvascular surgical disorder simultaneously remains
      controversial. To establish guidelines for the management of those patients, a
      retrospective review of patients who had concomitant AAA and intraabdominal
      nonvascular surgical disorders was undertaken. During the period January 1988 to
      December 1997 a series of 162 patients underwent surgical repairs of AAA in our
      hospital. Among them 16 patients (9.9%) had several kinds of intraabdominal
      nonvascular surgical disorders, and 13 underwent one-stage operation for both
      diseases. That is, cholelithiasis coexisted in five patients, inguinal hernia in
      four, gastric cancer in two, and retroperitoneal tumor and renal tumor in one
      each. All AAAs were the infrarenal type, and there were no inflammatory or
      ruptured aneurysms. In cases of cholelithiasis coexistent with AAA,
      aneurysmectomy was performed first. After tight closure of the retroperitoneum,
      cholecystectomy was done. In cases of cholelithiasis coexistent with AAA,
      aneurysmectomy was performed first. After tight closure of the retroperitoneum,
      cholecystectomy was done. In cases of inguinal hernia coexistent with AAA, the
      AAA was first replaced with a prosthetic vascular graft and a residual piece of
      the graft was used as a patch for hernioplasty. This procedure was similar to
      laparoscopic hernioplasty. In two cases of gastric cancer concomitant with AAA,
      the AAA was first replaced. Subtotal gastrectomy with D2 lymphatic dissection was
      done after tight closure of the retroperitoneum. A drain was inserted into the
      epiploic foramen to detect anastomotic leakage. A retroperitoneal tumor
      coexisting with AAA was dissected and resected en bloc with the aneurysmal wall
      because the tumor firmly adhered to the aneurysm. The abdominal aorta was then
      replaced with a prosthetic graft. In a case of renal tumor concomitant with AAA,
      nephrectomy was done first to perform a complete lymphatic dissection around the
      renal artery. Then AAA repair was performed with a conventional procedure. There
      were no fatal complications, such as pneumonitis, hemorrhage, anastomotic
      leakage, or graft infection. All 13 patients were discharged from our hospital
      and are currently free from recurrence of malignancy or hernia. In summary,
      properly selected one-stage operations for intraabdominal nonvascular surgical
      disorders and AAA may be safe and bring physical and economic benefit to the
      patient.

PMID- 10085396
TI  - New minimally invasive surgical technique using arterial T-grafts for treatment
      of double-vessel coronary artery disease: experimental study.
AB  - Minimally invasive surgery has been used successfully in patients with single
      vessel coronary artery disease (CAD), but there are no clinical reports of
      surgical techniques for the treatment of multivessel disease in this field using
      both internal mammary arteries (IMAs). Therefore a canine model has been
      established to demonstrate the feasibility of a minimally invasive surgical
      treatment of coronary artery double-vessel disease using both IMAs. Ten mongrel
      dogs underwent bilateral thoracoscopic preparation of both internal mammary
      arteries through small left lateral chest ports. Using the Port Access
      endovascular cardiopulmonary bypass system the right IMA (RIMA) was anastomosed
      as a free graft end-to-side to the left IMA (LIMA) as a T-graft. After induction
      of cardioplegic arrest the RIMA was anastomosed to the circumflex artery and the
      LIMA to the left anterior descending artery. All animals were weaned from
      cardiopulmonary bypass without inotropic support. The electrocardiogram showed
      sinus rhythm with no signs of ischemia. Intraoperative coronary angiography
      demonstrated patency of all anastomoses. The minimally invasive surgical
      treatment of double-vessel CAD using arterial T-grafts of both IMAs is thus
      feasible. Surgical trauma can be further reduced by harvesting the RIMA
      transmediastinally through the left lateral chest.

PMID- 10085397
TI  - Clinical experience with minimally invasive coronary artery and mitral valve
      surgery with the advantage of cardiopulmonary bypass and cardioplegic arrest
      using the Port Access technique.
AB  - To minimize surgical trauma, the use of Port Access cardiac surgery was initiated
      in patients (pts) with coronary artery disease (CAD) (42 pts) or mitral valve
      disease (MVD) (24 pts) in March 1996 at our institution. Altogether 42 pts (36
      men, 6 women; age 31-75 years, median 59.0 years) with isolated lesions of the
      left anterior descending (LAD) artery underwent Port Access coronary artery
      surgery (PACAS). A small (5-9 cm) incision was done parasternally on top on the
      fourth rib. The left internal mammary artery (LIMA) was dissected through the
      minithoracotomy or by using an additional thoracoscopic approach. A total of 24
      pts (12 men, 12 women; age 30-75 years, median 62 years) underwent Port Access
      mitral valve surgery (PAMVS). In these pts the procedure was performed through a
      small right thoracotomy (6-8 cm). In all cases, endovascular cardiopulmonary
      bypass (CPB) was instituted through femoral cannulation, and an additional
      endoaortic balloon catheter was introduced into the ascending aorta for aortic
      occlusion. In pts with PACAS the survival was 98% (41/42) and in the PAMVS group
      100%. All pts but one survived the PACAS and are well today. There were no deaths
      in the PAMVS group. The hospital stay was reduced by 1 day on average after PACAS
      and 3 days after PAMVS. Thus in well selected patients Port Access cardiac
      surgery represents a safe and feasible minimally invasive surgical approach that
      avoids the potential complications of a sternotomy while offering the advantages
      and safety of CPB and cardioplegic arrest. This minimally invasive approach
      offers a shortened hospital stay and earlier rehabilitation.

PMID- 10085398
TI  - Total esophagectomy versus proximal esophagectomy for esophageal cancer at the
      cervicothoracic junction.
AB  - To investigate the adequate extent of esophagectomy and lymphadenectomy for an
      esophageal cancer localized at the cervicothoracic junction, the mortality and
      morbidity rates, survival rates, and patterns of recurrence were retrospectively
      analyzed in two groups-14 patients who underwent total esophagectomy with or
      without laryngectomy and 15 patients who underwent proximal esophagectomy with or
      without laryngectomy-at Kurume University Hospital from 1981 to 1996. Proximal
      esophagectomy with or without laryngectomy resulted in a lower hospital mortality
      rate and better overall survival for patients who underwent curative
      esophagectomy compared with total esophagectomy with or without laryngectomy.
      Multivariate analysis indicated that the extent of esophagectomy (total
      esophagectomy versus proximal esophagectomy) was not a prognostic factor. The
      incidence of recurrence was not different between the two groups. Lymph node
      metastasis or recurrence from such esophageal cancers was localized to the neck
      and upper mediastinum. For an esophageal cancer localized at the cervicothoracic
      junction, therefore, proximal esophagectomy with or without laryngectomy and with
      cervical and upper mediastinal lymphadenectomy could be better indicated for
      preselected patients.

PMID- 10085399
TI  - Comparison of prognostic significance of nodal staging between old (4th edition)
      and new (5th edition) UICC TNM classification for gastric carcinoma.
      International Union Against Cancer.
AB  - The description of nodal staging for gastric cancer was changed in the new fifth
      edition of the International Union Against Cancer (UICC) TNM classification from
      the anatomic sites of metastatic lymph nodes to the number of metastatic lymph
      nodes, as pN1 is metastasis in 1 to 6 lymph nodes, pN2 is in 7 to 15 lymph nodes,
      and pN3 is in 16 or more lymph nodes. The purpose of this study was to
      investigate the prognostic significance of the new staging system based on the
      number of metastatic lymph nodes compared to the old staging system by anatomic
      site. From 1987 to 1994 a total of 2108 patients who underwent potentially
      curative resections with D2 or D3 lymph node dissection and with 15 or more lymph
      nodes retrieved were studied retrospectively. Lymph node metastases were found in
      1018 patients (48.3%). A mean of 37.9 lymph nodes were retrieved per patient, and
      a mean of 7.2 lymph nodes were invaded by tumor cells. We found that the new
      nodal staging based on the number of metastatic lymph nodes closely correlated
      with the depth of cancer invasion and with the old nodal staging based on the
      anatomic site of the metastatic nodes, with statistical significance. The 5-year
      survival rates after gastrectomy decreased significantly by increasing the extent
      of the pN classification in both nodal staging methods. In a subgroup analysis of
      survivals between the old and new nodal staging, the new classification showed
      more homogeneous survival at the same stage than the old one. With a multivariate
      analysis of prognostic factors, including the old and new nodal staging, the
      depth of invasion and the new nodal stage were the most significant prognostic
      factors, followed by the old nodal stage. Our data suggested that the new nodal
      staging based on the number of metastatic lymph nodes is not only a reliable and
      objective method for nodal classification, but it is also a significant
      prognostic determinant for gastric cancer that can be used in practice.

PMID- 10085400
TI  - Clinicopathologic study of gastric cancer based on Dukes' classification.
AB  - Dukes' classification is a useful staging system in patients with colorectal
      cancer. The aim of this study was to present clinicopathologic characteristics
      and survival of patients with gastric cancer based on Dukes' classification. A
      total of 273 patients with gastric cancer curatively treated by radical
      gastrectomy and lymph node dissection (D2, D3) were studied. With the modified
      Dukes' classification, A includes tumors limited to the mucosa, submucosa, or
      muscularis propria; B includes tumors extending into the subserosa or serosa; Ca
      includes tumors with one to six positive lymph nodes; and Cb includes tumors with
      seven or more positive lymph nodes. Dukes' classification modified by the number
      of positive lymph nodes well correlated with the tumor size (p < 0.01), depth of
      wall invasion (p < 0.01), level of lymph node metastasis (p < 0.01), and degree
      of lymphatic permeation (p < 0.01) and venous permeation (p< 0.01). The 5-year
      survival rate was significantly different among Dukes' A (98%), Dukes' B (90%),
      Dukes' Ca (75%), and Dukes' Cb (44%) cases. The results indicate that Dukes'
      classification modified by the number of positive lymph nodes (Dukes' A, B, Ca,
      an Cb) significantly correlates with tumor progression and patient survival; and
      it may be a simple and useful staging system for gastric cancer.

PMID- 10085401
TI  - Quality of life following radical surgical treatment of gastric carcinoma.
AB  - Quality of life (QOL) in patients with gastric cancer who underwent total
      gastrectomy has so far not been studied using the EORTC QLQ-C30 (Quality of Life
      Core Questionnaire of the European Organization for Research and Treatment of
      Cancer) as a standardized European QOL instrument. The aim of this study was to
      evaluate the effect of radical procedures such as extensive lymph node resection
      and combined resection of adjacent organs on patients' QOL. From 1992 to 1996,
      152 patients underwent total gastrectomy. All patients alive on July 1, 1996 were
      included in the study (77/152). For assessing QOL, the EORTC QOL questionnaire
      QLQ-C30 version 2.0 and a validated gastric cancer module were sent home to the
      patients for self-completion. The response rate was 91%. It was possible to
      evaluate the questionnaires of 62 patients who had undergone resection with
      curative intent including 13 extended gastrectomies (21%). Of the 62 resections,
      50 were combined with D2 lymphadenectomy (80.6%). The global health status was
      not negatively influenced by D2 lymphadenectomy and extended gastrectomy.
      Patients with splenectomy were more affected by treatment than patients without
      splenectomy. Radical gastrectomy combined with D2 lymphadenectomy is the
      treatment of choice for gastric cancer patients, concerning not just survival but
      QOL as well.

PMID- 10085402
TI  - Rectal cancer surgery in a district general hospital: controlled follow-up study.
AB  - Local recurrence after curative surgery of rectal cancer indicates failure of the
      initial treatment. In recent years reported local recurrence rates have steadily
      decreased. In this study 364 patients treated for rectal cancer were analyzed
      retrospectively to determine if it is still justified to treat this disease in
      small nonspecialized hospitals. An overall local recurrence rate of 9.7% was
      found for all operation methods used. Local recurrence rates were 11.6% for
      patients treated by low anterior resection, 8.4% for the patients who sustained
      an amputation of the rectum, and 7.1% for the patients treated by transanal tumor
      resection. None of the patients in whom we performed a total mesorectal excision
      has developed local recurrent disease during the observation period. Careful
      surgical technique and close follow-up of the patients being prerequisites, the
      results of this study justify continuing to treat rectal cancer in nonspecialized
      centers.

PMID- 10085403
TI  - Tribute to a triad: history of splenic anatomy, physiology, and surgery-part 2.

PMID- 10085404
TI  - Minimally invasive transcylindrical cholecystectomy.

PMID- 10085405
TI  - CD40-CD154 interaction in experimental and human disease (review).
AB  - Cell-to-cell signals between T lymphocytes and antigen-presenting cells strictly
      regulate the development of the immune response. It has clearly emerged that
      among these signals few cell surface receptor-ligand pairs, such as CD40 and its
      ligand, CD154, are mandatory for the induction of lymphocyte activation. The
      early observation that mutations of CD154 gene are responsible for a human severe
      immunodeficiency primed an impressive number of studies aimed to functionally
      characterize this receptorial system in view of therapeutically exploiting its
      properties. Indeed, various approaches aimed to disrupt natural CD40-CD154
      interaction were highly effective in the prevention and treatment of several
      experimental models of autoimmune disease and transplant rejection. In parallel,
      abnormalities of this pathway were constantly found in several immunologically
      mediated human diseases. Furthermore, a number of studies have dissected the role
      of CD40 and its ligand in the immune response against various microbial and viral
      pathogens. Since these molecules are often expressed by tumor cells, it is not
      surprising that great efforts have been made to address their function also in
      the development of cancer. Most recent data strongly suggest an involvement of
      endothelial CD40 in the vascular processes that lead to atherogenesis. This
      review focuses on the most significant advances in the understanding of the
      molecular regulatory events involving CD40 and its ligand in experimental and
      human disease.

PMID- 10085406
TI  - Vitamin D and retinoids in parathyroid glands (review).
AB  - Vitamin D and retinoids are important regulators of differentiation and
      proliferation in a number of tissues, and have been implicated as chemopreventive
      agents in several different tumors. While vitamin D is known to be important for
      regulation of parathyroid function and proliferation, it has recently been
      established that parathyroid cells also are targets for retinoids.
      Hyperparathyroidism (HPT) is a common disorder, and evaluation of the disease has
      indicated high prevalence of subclinical disease, as well as clear benefits of
      offering treatment for the disease. This review summarizes the data so far
      gathered concerning parathyroid cells, vitamin D and retinoids, with clear
      implication on prospects of possible medical treatment of hyperparathyroidism.

PMID- 10085407
TI  - Thrombin interaction with platelet GpIb: structural mapping and effects on
      platelet activation (review).
AB  - Platelet glycoprotein Ib (GpIb) is an integral platelet membrane glycoprotein
      which plays a major role in haemostasis, being involved in both von Willebrand
      factor (vWF) and alpha-thrombin high affinity binding. Such interactions
      contribute to the early adhesion of platelets to exposed subendothelium and to
      the process of platelet activation. Glycoprotein Ib belongs to the so called
      <leucine rich repeat> (LRR) family of proteins, characterized by a structural
      motif consisting of the presence of one or more tandem LRRs, flanked by conserved
      sequences. Several experimental strategies have recently documented the
      involvement of the thrombin domain referred to as 'heparin binding site' in the
      binding to GpIb. This review is aimed at reporting on the structural mapping of
      both alpha-thrombin and GpIb domains involved in such interaction and on possible
      roles of thrombin-GpIb binding on the mechanisms supporting the platelet
      activation.

PMID- 10085408
TI  - Proliferative fraction, bcl-1 gene translocation, and p53 mutation status as
      markers in mantle cell lymphoma.
AB  - The molecular genetic hallmark of mantle cell lymphomas (MCL) is the reciprocal
      translocation t(11;14)(q13;q32) which juxtaposes the bcl-1 proto-oncogene to one
      of the joining segments of the immunoglobulin heavy chain gene. This
      translocation is very common in MCL and occurs in up to 70% of these
      malignancies. Due to the aggressive nature of MCL, markers identifying tumor
      progression and clinical outcomes are necessary. In this study we examined
      whether a corroborative relation exists between p53 mutations, bcl-1
      translocation, and the proliferative fraction in MCL. We evaluated the
      proliferative fraction, p53 gene status, and bcl-1 translocation in 21 patients
      with confirmed MCL. Controls consisted of normal DNA and 7 B-cell lymphomas.
      Immunohistochemical detection of Ki-67 was used to assess proliferative activity
      while molecular techniques were used to detect p53 mutations and the bcl-1 gene
      translocation. Reactivity to the monoclonal antibody Ki-67 on neoplastic cells
      ranged from 5% to 40% in typical MCL cases. The bcl-1 gene translocation was
      detected by PCR in 48% (10/21) of MCLs while no rearrangements were detected by
      PCR in case control DNA. Screening exons 5-8 of the p53 gene for mutations did
      not identify a single mutation in any of the MCL cases. No correlation was found
      between p53 mutations, the presence of a bcl-1 translocation, and the
      proliferative activity of neoplastic MCL cells. We conclude that these markers
      may demonstrate independent events which occur during the pathogenesis of MCL.

PMID- 10085409
TI  - Application of preformed hammerhead ribozymes in the gene therapy of cancer
      (review).
AB  - Inhibition of gene expression is an important experimental method to determine
      the function of genes, and could have a great impact upon the treatment of
      diseases in which gene products are involved. Catalytic RNAs (ribozymes) with
      endoribonuclease activity are RNA molecules that site-specifically cleave other
      RNAs, and thus have tremendous potential as novel therapeutic agents. The
      capacity of these agents to suppress gene expression in a wide range of systems
      strengthens the importance of this novel gene-based therapy, and indicate that
      preformed ribozymes may be useful as pharmaceuticals.

PMID- 10085410
TI  - Cloning and functional analysis of anti-double strand DNA IgG autoantibodies
      using the phage-display method.
AB  - To examine the relationship between pathophysiological effects and molecular
      features of anti-double-stranded (ds)DNA autoantibodies (Abs), we isolated anti
      dsDNA Ab fragments by using the phage-display method. Fd c and light-chain DNA
      were PCR amplified from peripheral blood lymphocytes of a patient with systemic
      lupus erythematosus (SLE), complicated with lupus nephritis. They were then
      inserted into a phagemid vector, pComb3-H. We generated eight Fab fragments that
      specifically bound to solid-phase DNA. The Fab clones stained positively using
      Crithidia luciliae, indicating that they were anti-dsDNA antibodies. Nucleotide
      sequences of VH of Fab clones were very similar and appeared to be derived from
      VH26 germline gene. Differences in the activities of anti-dsDNA Ab of the Fab
      clones may be ascribed to the diversity of VL. Fab fragments with anti-dsDNA Ab
      activities exhibited a positive charge on isoelectric focusing, consistent with
      pathogenic features. Our results indicate that anti-dsDNA Ab Fab fragments
      obtained by the phage-display method in the present study may possess molecular
      and functional characteristics of pathogenic anti-dsDNA autoAbs in SLE.

PMID- 10085411
TI  - Damage to DNA purified from the radioresistant prokaryote, Deinococcus
      radiodurans, by acid heating.
AB  - Using a highly radioresistant bacterium, Deinococcus radiodurans, the mechanism
      of degradation of the purified DNA molecules by heating was examined under acidic
      conditions. Setting the treatment temperature at 55uC with a duration of 0 to 20
      min and adjusting the pH of the cell suspension to 3, 5 or 7, cell viabilities
      after the treatment were compared. The survival rate decreased in proportion to
      the reduction of pH. DNA purified from D. radiodurans was then damaged by
      irradiation with gamma-rays at 0.22 kGy or 1 kGy. It was considered that the
      radioresistance of D. radiodurans was due to its high repair capability, rather
      than any specificity of DNA structure. Purified D. radiodurans DNA was resistant
      to heating up to 90uC at neutral pH. However, marked DNA damage occurred when it
      was heated at pH values below 5.0. Then, DNA labeled with [3H]adenine was
      examined. Treatment at lower pH and higher temperature resulted in release of
      more adenine base, i.e., the purine ring, from the DNA molecules. Therefore, we
      assumed that the decrease in survival of D. radiodurans in vivo and damage to its
      DNA in vitro by acid heating were due to the release of adenine and guanine from
      the DNA, i.e., depurination.

PMID- 10085412
TI  - Enhanced HIV-1 envelope-tumor protection by a recombinant vaccinia virus
      expressing anchored HIV-1 gp120 lacking gp41.
AB  - A recombinant vaccinia virus (rvv) expressing, human immunodeficiency virus type
      1 (HIV-1) external envelope glycoprotein, gp120, fused to a non-cleavable
      transmembrane protein, vvE13, elicited protection against a tumor cell line
      expressing HIV-1 full length envelope glycoprotein, gp160, in mice. Mice
      vaccinated with vvE13 exhibited a decreased incidence of tumor development and
      significantly smaller tumors in comparison to mice vaccinated with rvv gp160,
      vvE1, or a thymidine kinase minus (TK-) rvv, vSC11, or phosphate-buffered saline
      (PBS) injected controls. vvE13 and vvE1 also delayed tumor development, compared
      to vSC11 and PBS-injected controls; however, a statistical correlation could not
      be demonstrated due to the development of tumors in so few animals. Specificity
      toward HIV-1 envelope glycoprotein, was shown, since HIV-1 envelope-tumor
      prevention (incidence for vvE13 and size for vvE1 and vvE13 and delay for vvE1
      and vvE13) was statistically superior with HIV-1 envelope expressing tumors
      compared to parenteral tumors. The vvE13 recombinant vaccinia virus expressing
      the HIV-1 envelope glycoprotein gp120 fused to a non-cleavable transmembrane
      protein elicits superior protection against tumors expressing the gp160 envelope
      glycoprotein, as compared to vvE1 expressing gp160.

PMID- 10085413
TI  - Expression of heat shock protein 70 in leukocytes of patients with sepsis.
AB  - The heat shock proteins are known to protect cells against diverse injuries such
      as cytotoxicity by TNFalpha acting mainly as chaperones for denatured proteins.
      Lipopolysaccharide stimulates the production and the release of numerous
      endogenous mediators of sepsis: tumor necrosis factor alpha, interleukin-1, and
      interleukin-6 that induce fever production. Moreover, temperature at 40 degrees C
      is sufficient to induce heat shock and attenuate both TNFalpha and IL-1
      expression. We demonstrate a distinct profile in gene expression of HSP 70 family
      in leukocytes obtained from different phases of septic patients. Our findings
      strongly suggest that HSP 70 may play a role in the outcome of septic shock
      patients.

PMID- 10085414
TI  - Plasticity-related serine proteases in the brain (review).
AB  - Serine proteases exert a variety of functions in the body; food digestion,
      regulation of other proteins and modification of extracellular matrix. Cumulative
      evidence has shown the importance of serine proteases in the nervous system as
      well. It has been shown that three serine proteases, thrombin, plasminogen
      activators and neuropsin, have functional roles in neural plasticity. Most of the
      actions of thrombin are thought to be mediated by its specific receptors.
      Thrombin reverses neurite outgrowth of serum-deprived neuroblastoma cells, and
      induces protective and apoptotic effects on neurons and glial cells depending on
      concentration and time. Tissue-type and urokinase-type plasminogen activators
      (tPA and uPA) distribute broadly in the brain. tPA and uPA exert a variety of
      functions during development. These proteases also function in long-term
      potentiation and kindling formation. Furthermore, tPA is essential to excitotoxic
      neuronal cell death. Neuropsin is a serine protease expressed in the limbic
      system of the brain. Kindling induced neuropsin mRNA and protein expression and
      anti-neuropsin antibody ameliorates kindling epilepsy. The possible roles of
      these proteases in neural plasticity are reviewed here.

PMID- 10085415
TI  - Abnormal binding pattern and composition of the NF-kappaB complex components are
      involved in increased TNF-alpha production by tumor bearer B cells.
AB  - B lymphocytes from mammary tumor bearers are cytotoxic against tumor targets and
      produce TNF-alpha. A greater stability of RNA and a decreased rate of RNA
      degradation was observed in B cells of tumor bearers compared to those of normal
      mice. The TNF-alpha promoter contains regions that bind NF-kappaB, which regulate
      the rate of transcription. Supershift assays for the NF-kappaB region showed that
      there are p50-p65 heterodimers and p50 homodimers in the nuclear extracts of the
      two types of B cells, while those from tumor bearers lack the c-Rel component
      that is present in normal B cells. These results indicate that abnormalities in
      binding and composition of the NF-kappaB complexes may be involved in the
      increased TNF-alpha production by B cells of tumor bearers.

PMID- 10085416
TI  - The role of the detection of hematogenous micrometastasis in prostate
      adenocarcinoma and malignant melanoma by RT-PCR.
AB  - Recent studies reported the possibility of detecting prostate adenocarcinoma and
      malignant melanoma cells in peripheral blood using RT-PCR of prostatic specific
      antigen (PSA), prostatic specific membrane antigen (PSMA) and Tyrosinase mRNAs.
      The PCR results showed high variability, ranging between 0% and 100% of
      positivity in patients with advanced disease. Our purpose was to evaluate the
      presence of tumor marker mRNAs in peripheral blood of prostate cancer and
      melanoma patients by means of RT-nested-PCR. We tested 70 and 36 peripheral blood
      samples from prostate carcinoma and malignant melanoma patients, respectively.
      The RT-PCR analysis showed the presence of PSA cDNA in 9 out of 70 (12.9%); PSMA
      cDNA in 14 out of 70 (20%); and Tyrosinase cDNA in 2 out of 36 (5.5%) peripheral
      blood samples from melanoma patients. Our study confirms the applicability of
      this sensitive method to monitor disease status. Although, the RT-nested-PCR of
      Tyrosinase is able to detect neoplastic cells in peripheral blood specimens, we
      suggest the necessity of a great caution in interpreting PCR results when the
      nested method has been used.

PMID- 10085417
TI  - Signaling pathway and pepsinogen secretion in Helicobacter pylori-infected human
      gastric adenocarcinoma.
AB  - Although in vitro studies have suggested that Helicobacter pylori not only
      attaches to cultured cells but also induces signal transduction events in host
      cells, the underlying mechanism of H. pylori action has yet to be fully
      investigated. In the present study, a cytotoxin-positive H. pylori was used to
      infect and examined for its effect on the stimulation of second messengers in
      human gastric adenocarcinoma (AGS). Results showed that H. pylori increased
      cytosolic free calcium concentration [Ca2+]i in host cells in a dose-dependent
      manner. The increase of [Ca2+]i was due to release from the intracellular Ca2+
      store as well as entry to the extracellular Ca2+. H. pylori infection on host
      cells was also found to induce the generations of inositol phosphates, adenosine
      3', 5'-cyclic monophosphate, and guanosine 3',5'-cyclic monophosphate, and to
      stimulate the secretion of pepsinogen.

PMID- 10085418
TI  - Cell-dependent functional roles of HIV-1 Nef for virus replication (review).
AB  - The stage in the human immunodeficiency virus type 1 (HIV-1) replication cycle
      that is affected by Nef has been investigated. Nef is dispensable during the
      transcription to virion production step. In contrast, Nef is critical in the
      early phase of the virus replication cycle, from virion adsorption to
      integration. Furthermore, virions produced in the absence of Nef have been
      demonstrated to be inefficient to complete the virus DNA synthesis. When virions
      are produced in particular cells without Nef, they exhibit a severe defect in the
      virus entry process into cells. Taken together, it is concluded that HIV-1 Nef
      acts via modulation of viral particles to enhance virus infectivity in a cell
      dependent manner.

PMID- 10085419
TI  - Apolipoprotein E genotype has no effect on the free intracellular Ca2+
      concentration of platelets from Alzheimer's disease patients.
AB  - The free intracellular Ca2+ concentration [Ca2+]i of platelets was investigated
      in Alzheimer's disease (AD) patients and age-matched control subjects with
      distinct Apo E genotypes. No significant differences were found between the Apo E
      genotype and the [Ca2+]i levels of platelets (basal and alpha-thrombin
      stimulated) from AD patients and age-matched control subjects, suggesting that
      [Ca2+]i homeostasis of platelets from AD patients is independent of the Apo E
      genotype. The results are discussed in terms of involvement of Apo E and [Ca2+]i
      changes in the etiopathogenesis of AD.

PMID- 10085420
TI  - Statistical analysis of the age-adjusted incidence rates of human neoplasias:
      changes in time and space from early 1960's to mid 1980's with special reference
      to the steroid criminal hypothesis of carcinogenesis.
AB  - Our earlier reports indicated that the changes of age-adjusted incidence rates
      (AAIRs) of any 2 tumors in time and space, as investigated by the sequential
      regression analysis, showed a good fitness to the equilibrium model under the
      control of the law of mass action. The purpose of this study is to investigate
      the problem of whether or not the changes of AAIRs of individual tumors in time
      and space show a similar fitness to the equilibrium model of the law of mass
      action. The cancer risk data set of: a) 20 neoplasias in scope; b) 6 cancer
      registration areas in space; and c) 5 sequential investigations from early 1960's
      to mid 1980's in time, were subjected to the sequential regression analysis - a
      modification of the least square method. Results obtained are as follows: a) out
      of 20 tumors tested, all tumors other than 5 tumor types showed a good fitness
      (P<0.05) to the equilibrium model of the law of mass action in their risk changes
      in space. The 5 tumor types that failed to fit to the equilibrium model were male
      gall-bladder cancer, male breast cancer, male thyroid cancer, female liver cancer
      and female laryngeal cancer. They were all classified as the members of low-risk
      gender in the cancer family with sex discrimination of cancer risk. b) All tumors
      other than male thyroid cancer of Birmingham-England showed a good fitness to the
      equilibrium model of the law of mass action in their risk changes in time. c) It
      is argued that the good fitness to the equilibrium model of the law of mass
      action and the poor fitness to the equilibrium model can be taken each as
      indication of the predominant expression of oncogene activation and the emergence
      of intervention of tumor suppressor gene inactivation to the full expression of
      oncogene activation in the mathematical structure of the cancer risk data set.
      The significance of the above findings as the supporting evidence of the steroid
      criminal hypothesis of carcinogenesis as well as the pertinence of the least
      square method to the mathematical analysis of cancer risk are discussed in the
      light of historical development of science from early 19th century to late 20th
      century.

PMID- 10085421
TI  - A cerebellar model of timing and prediction in the control of reaching.
AB  - A simplified model of the cerebellum was developed to explore its potential for
      adaptive, predictive control based on delayed feedback information. An abstract
      representation of a single Purkinje cell with multistable properties was
      interfaced, using a formalized premotor network, with a simulated single degree
      of-freedom limb. The limb actuator was a nonlinear spring-mass system based on
      the nonlinear velocity dependence of the stretch reflex. By including realistic
      mossy fiber signals, as well as realistic conduction delays in afferent and
      efferent pathways, the model allowed the investigation of timing and predictive
      processes relevant to cerebellar involvement in the control of movement. The
      model regulates movement by learning to react in an anticipatory fashion to
      sensory feedback. Learning depends on training information generated from
      corrective movements and uses a temporally asymmetric form of plasticity for the
      parallel fiber synapses on Purkinje cells.

PMID- 10085422
TI  - Improved multidimensional scaling analysis using neural networks with distance
      error backpropagation.
AB  - We show that neural networks, with a suitable error function for backpropagation,
      can be successfully used for metric multidimensional scaling (MDS) (i.e.,
      dimensional reduction while trying to preserve the original distances between
      patterns) and are in fact able to outdo the standard algebraic approach to MDS,
      known as classical scaling.

PMID- 10085423
TI  - Firing rate distributions and efficiency of information transmission of inferior
      temporal cortex neurons to natural visual stimuli.
AB  - The distribution of responses of sensory neurons to ecological stimulation has
      been proposed to be designed to maximize information transmission, which
      according to a simple model would imply an exponential distribution of spike
      counts in a given time window. We have used recordings from inferior temporal
      cortex neurons responding to quasi-natural visual stimulation (presented using a
      video of everyday lab scenes and a large number of static images of faces and
      natural scenes) to assess the validity of this exponential model and to develop
      an alternative simple model of spike count distributions. We find that the
      exponential model has to be rejected in 84% of cases (at the p < 0.01 level). A
      new model, which accounts for the firing rate distribution found in terms of slow
      and fast variability in the inputs that produce neuronal activation, is rejected
      statistically in only 16% of cases. Finally, we show that the neurons are
      moderately efficient at transmitting information but not optimally efficient.

PMID- 10085424
TI  - Collective behavior of networks with linear (VLSI) integrate-and-fire neurons.
AB  - We analyze in detail the statistical properties of the spike emission process of
      a canonical integrate-and-fire neuron, with a linear integrator and a lower bound
      for the depolarization, as often used in VLSI implementations (Mead, 1989). The
      spike statistics of such neurons appear to be qualitatively similar to
      conventional (exponential) integrate-and-fire neurons, which exhibit a wide
      variety of characteristics observed in cortical recordings. We also show that,
      contrary to current opinion, the dynamics of a network composed of such neurons
      has two stable fixed points, even in the purely excitatory network, corresponding
      to two different states of reverberating activity. The analytical results are
      compared with numerical simulations and are found to be in good agreement.

PMID- 10085425
TI  - Recurrent sampling models for the Helmholtz machine.
AB  - Many recent analysis-by-synthesis density estimation models of cortical learning
      and processing have made the crucial simplifying assumption that units within a
      single layer are mutually independent given the states of units in the layer
      below or the layer above. In this article, we suggest using either a Markov
      random field or an alternative stochastic sampling architecture to capture
      explicitly particular forms of dependence within each layer. We develop the
      architectures in the context of real and binary Helmholtz machines. Recurrent
      sampling can be used to capture correlations within layers in the generative or
      the recognition models, and we also show how these can be combined.

PMID- 10085426
TI  - Feature extraction through LOCOCODE.
AB  - Low-complexity coding and decoding (LOCOCODE) is a novel approach to sensory
      coding and unsupervised learning. Unlike previous methods, it explicitly takes
      into account the information-theoretic complexity of the code generator. It
      computes lococodes that convey information about the input data and can be
      computed and decoded by low-complexity mappings. We implement LOCOCODE by
      training autoassociators with flat minimum search, a recent, general method for
      discovering low-complexity neural nets. It turns out that this approach can unmix
      an unknown number of independent data sources by extracting a minimal number of
      low-complexity features necessary for representing the data. Experiments show
      that unlike codes obtained with standard autoencoders, lococodes are based on
      feature detectors, never unstructured, usually sparse, and sometimes factorial or
      local (depending on statistical properties of the data). Although LOCOCODE is not
      explicitly designed to enforce sparse or factorial codes, it extracts optimal
      codes for difficult versions of the "bars" benchmark problem, whereas independent
      component analysis (ICA) and principal component analysis (PCA) do not. It
      produces familiar, biologically plausible feature detectors when applied to real
      world images and codes with fewer bits per pixel than ICA and PCA. Unlike ICA, it
      does not need to know the number of independent sources. As a preprocessor for a
      vowel recognition benchmark problem, it sets the stage for excellent
      classification performance. Our results reveal an interesting, previously ignored
      connection between two important fields: regularizer research and ICA-related
      research. They may represent a first step toward unification of regularization
      and unsupervised learning.

PMID- 10085427
TI  - Discontinuities in recurrent neural networks.
AB  - This article studies the computational power of various discontinuous real
      computational models that are based on the classical analog recurrent neural
      network (ARNN). This ARNN consists of finite number of neurons; each neuron
      computes a polynomial net function and a sigmoid-like continuous activation
      function. We introduce arithmetic networks as ARNN augmented with a few simple
      discontinuous (e.g., threshold or zero test) neurons. We argue that even with
      weights restricted to polynomial time computable reals, arithmetic networks are
      able to compute arbitrarily complex recursive functions. We identify many types
      of neural networks that are at least as powerful as arithmetic nets, some of
      which are not in fact discontinuous, but they boost other arithmetic operations
      in the net function (e.g., neurons that can use divisions and polynomial net
      functions inside sigmoid-like continuous activation functions). These arithmetic
      networks are equivalent to the Blum-Shub-Smale model, when the latter is
      restricted to a bounded number of registers. With respect to implementation on
      digital computers, we show that arithmetic networks with rational weights can be
      simulated with exponential precision, but even with polynomial-time computable
      real weights, arithmetic networks are not subject to any fixed precision bounds.
      This is in contrast with the ARNN that are known to demand precision that is
      linear in the computation time. When nontrivial periodic functions (e.g.,
      fractional part, sine, tangent) are added to arithmetic networks, the resulting
      networks are computationally equivalent to a massively parallel machine. Thus,
      these highly discontinuous networks can solve the presumably intractable class of
      PSPACE-complete problems in polynomial time.

PMID- 10085428
TI  - Parameter convergence and learning curves for neural networks.
AB  - We revisit the oft-studied asymptotic (in sample size) behavior of the parameter
      or weight estimate returned by any member of a large family of neural network
      training algorithms. By properly accounting for the characteristic property of
      neural networks that their empirical and generalization errors possess multiple
      minima, we rigorously establish conditions under which the parameter estimate
      converges strongly into the set of minima of the generalization error.
      Convergence of the parameter estimate to a particular value cannot be guaranteed
      under our assumptions. We then evaluate the asymptotic distribution of the
      distance between the parameter estimate and its nearest neighbor among the set of
      minima of the generalization error. Results on this question have appeared
      numerous times and generally assert asymptotic normality, the conclusion expected
      from familiar statistical arguments concerned with maximum likelihood estimators.
      These conclusions are usually reached on the basis of somewhat informal
      calculations, although we shall see that the situation is somewhat delicate. The
      preceding results then provide a derivation of learning curves for generalization
      and empirical errors that leads to bounds on rates of convergence.

PMID- 10085429
TI  - Analog neural nets with gaussian or other common noise distribution cannot
      recognize arbitrary regular languages.
AB  - We consider recurrent analog neural nets where the output of each gate is subject
      to gaussian noise or any other common noise distribution that is nonzero on a
      sufficiently large part of the state-space. We show that many regular languages
      cannot be recognized by networks of this type, and we give a precise
      characterization of languages that can be recognized. This result implies severe
      constraints on possibilities for constructing recurrent analog neural nets that
      are robust against realistic types of analog noise. On the other hand, we present
      a method for constructing feedforward analog neural nets that are robust with
      regard to analog noise of this type.

PMID- 10085430
TI  - Discriminant component pruning. Regularization and interpretation of multi
      layered back-propagation networks.
AB  - Neural networks are often employed as tools in classification tasks. The use of
      large networks increases the likelihood of the task's being learned, although it
      may also lead to increased complexity. Pruning is an effective way of reducing
      the complexity of large networks. We present discriminant components pruning
      (DCP), a method of pruning matrices of summed contributions between layers of a
      neural network. Attempting to interpret the underlying functions learned by the
      network can be aided by pruning the network. Generalization performance should be
      maintained at its optimal level following pruning. We demonstrate DCP's
      effectiveness at maintaining generalization performance, applicability to a wider
      range of problems, and the usefulness of such pruning for network interpretation.
      Possible enhancements are discussed for the identification of the optimal reduced
      rank and inclusion of nonlinear neural activation functions in the pruning
      algorithm.

PMID- 10085431
TI  - Rheumatic manifestations preceding adult acute leukemia: characteristics and
      implication in course and prognosis.
AB  - The manifestations and outcome of adult patients with acute leukemia (AL) were
      examined to study the characteristics of the rheumatological prodrome of AL and
      to find whether it is a marker of a distinct clinical and laboratory course and
      whether it has any prognostic implication. During a 10-year period, 8/139 (5.8%)
      of AL patients presented with rheumatic manifestations. The average duration of
      the arthritis syndrome preceding the diagnosis of AL was 3.25 months. The most
      common pattern of presentation was a reactive arthritis-like syndrome involving
      the large joints asymmetrically and associated with low back pain. Distinctive
      features suggesting a paraneoplastic arthritis were severe pain disproportionate
      to physical findings, a poor response to conventional antirheumatic treatment,
      and early significant osteopenia or lytic bone lesions. The epidemiological,
      clinical and laboratory characteristics of patients with or without rheumatic
      manifestations were comparable, except for fever on presentation, the presence of
      transient metabolic derangement following chemotherapy, and the initial average
      hemoglobin, hematocrit and serum uric acid values. Moreover, the initial outcome
      of the two groups was similar, as the early mortality rates were comparable
      (42.8% vs. 45% for patients with or without arthritis, respectively). In
      conclusion, rheumatic syndrome presentation of adult AL is uncommon, and
      apparently has no deleterious effects on initial prognosis. A timely diagnosis
      requires an increased awareness to distinctive features.

PMID- 10085432
TI  - Storage of iron in bone marrow plasma cells. Ultrastructural characterization,
      mobilization, and diagnostic significance.
AB  - The physiological site of iron storage in the human bone marrow is the macrophage
      (orthotopic iron store). Iron-storing plasma cells, as bone marrow indicators of
      iron overload, and/or chronic alcoholism represent a pathological (heterotopic)
      iron store. They were demonstrated by light and electron microscopy in 23 iron
      overloaded patients: transfusional siderosis (n = 8), genetic haemochromatosis
      (GH; n = 11), iron-loading anaemias (n = 4) and in patients with bone marrow
      impairment due to chronic alcoholism (n = 6). The pattern of iron storage in bone
      marrow plasma cells was monitored during iron loading in patients receiving
      continuous transfusional therapy (n = 7) and also upon reversal of iron overload
      by repeated phlebotomies in GH (n = 9) and in iron-loading anaemias (n = 4). The
      first ultrastructural evidence of iron storage in plasma cells was the appearance
      of free ferritin molecules in the cytosol, thus indicating endogenous ferritin
      synthesis. Accumulation of iron proceeded with the additional formation of
      ferritin- and haemosiderin-containing lysosomes (siderosomes) in these cells.
      Lysosomal ferritin partially showed a paracrystalline array. The siderosomes
      originated from autophagocytosis of cytoplasmic areas containing free ferritin
      molecules. In addition, the formation of ferritin-containing vesicles in the
      proximity of the Golgi apparatus was observed. The heterotopic iron store of bone
      marrow plasma cells was less readily mobilizable by blood-letting than the
      orthotopic store of macrophages.

PMID- 10085433
TI  - Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic
      purpura.
AB  - 'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a
      well-known characteristic of patients with idiopathic thrombocytopenic purpura
      (ITP). Therefore, despite what may be severe thrombocytopenia these patients
      generally do not suffer from severe life-threatening hemorrhage. The plasma level
      of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet
      activation. Available data suggest that interleukin-6 (IL-6) may contribute to
      the regulation of megakaryocytopoiesis and platelet activity. The purpose of this
      study is to investigate the status and kinetics of IL-6 and selectins, which are
      involved in the platelet function, production, and immunologic functions, during
      the clinical course of ITP, that may be helpful for understanding the biology of
      the disease. Twenty-two ITP patients were studied prospectively in the course of
      their disease. Sixteen, 8 and 6 patients were available after platelet recovery,
      relapse and splenectomy, respectively. Fifteen healthy persons served as a
      control group. Higher levels of both sP-selectin and IL-6 were observed in all
      clinical stages of disease compared to the control group. However, more prominent
      elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001
      vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001
      vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin
      and soluble E-selectin levels were not different from the controls. Both sP
      selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely
      correlated with platelet count during disease course. There was a positive
      correlation between the sL-selectin level and leukocyte count (r = 0.60, p <
      0.001). These results suggest that residual platelets are activated in ITP, which
      offers a relatively benign clinical course compared to other thrombocytopenias.
      High IL-6 concentration during thrombocytopenia may be involved in compensatory
      megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.

PMID- 10085434
TI  - Familial aggregation of nonhematological malignancies in relatives of patients
      with hematological neoplasms.
AB  - Familial aggregation of nonhematological malignant disorders (NHMD) was compared
      in 189 families of patients with hematological neoplasms (HN) with a control
      group of 36 families of patients with benign hematological disorders and a second
      group of 33 families of patients with diabetes mellitus. A self-administered
      questionnaire was used requesting from each family a full list of first- and
      second-degree relatives, their vital status, current age or age at death, and a
      list of their chronic diseases, including all malignant disorders. There was no
      evidence of a significantly increased tendency for developing NHMD among
      relatives of patients with HN as compared to controls (adjusted odds ratio of
      0.88; 95% confidence interval 0.61-1.27). Moreover, in the HN group, no
      significant difference in the frequency of NHMD was found between the families
      with and without familial aggregation of HN. Based on the present analysis and
      our previous observations on familial aggregation of HN, we conclude that the
      increased aggregation of malignant disorders among relatives of patients with HN
      is unique to the hematopoietic system and might result from a genetic
      predisposition to HN in these families.

PMID- 10085435
TI  - Ultrastructural changes of erythrocyte membrane skeletons in chorea
      acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep
      etching method.
AB  - The shapes of acanthocytic erythrocytes have been thought to be related to
      changes of the organization of the membrane components. In this study,
      acanthocytes from a patient with chorea-acanthocytosis and a patient with McLeod
      syndrome were examined. These acanthocytes had a greater tendency to form spikes
      than normal erythrocytes in an incubation culture system, indicating their
      weakness against membrane tension. The membrane skeletons of erythrocytes from
      both patients were examined by our erythrocyte-splitting method followed by the
      quick-freezing and deep-etching method. The ultrastructural organization of the
      membrane skeletons was heterogeneous even in individual erythrocytes, indicating
      regional changes in the compactness of their meshworks. In the process of
      erythrocyte splitting, some erythrocyte membranes became reversed and protruded
      into the cytoplasmic side. In these regions, there were fewer filamentous
      structures. The focal membrane skeletal changes, which are probably one of the
      factors that induce the phenotype of an acanthocytic erythrocyte, were
      demonstrated for the first time by this method.

PMID- 10085436
TI  - Micronuclei and nuclear abnormalities observed in erythroblasts in
      myelodysplastic syndromes and in de novo acute leukemia after treatment.
AB  - The frequencies of erythroblasts with micronuclei (EBM) and erythroblasts with
      aberrant nuclear shapes (EBAN) in bone marrow were evaluated in 60 patients with
      untreated myelodysplastic syndrome (MDS), and also in 21 patients with acute
      leukemia before and after treatment, and the results were compared regarding
      cytogenetic patterns. In patients with acute leukemia, the frequencies of EBM and
      EBAN in bone marrow were 0.60 +/- 0.35% (mean +/- SD) and 1.2 +/- 1.1% before
      treatment, respectively, the former of which was higher than those obtained from
      93 patients with various nonmalignant diseases (p < 0.01). After treatment with
      antileukemic drugs, the mean values of them significantly increased 9.7 and 6.1
      times from the pretreatment ones, respectively. No correlation was found between
      the yields of EBM and EBAN and cytogenetic patterns, although regimens including
      administration of vincristine seemed to cause them more frequently. Most patients
      with MDS showed a consistent increase of EBM and EBAN at the time of diagnosis
      irrespective of the treatment; the mean frequencies were 7. 7 and 6.3 times
      higher than those obtained from patients with nonmalignant diseases,
      respectively. Furthermore, the numbers of EBM and EBAN were significantly higher
      in patients with an abnormal karyotype than those with a normal karyotype (p <
      0.05 for EBM and p < 0.001 for EBAN). In particular, 8 patients with a monosomy
      7q showed a marked increase of EBAN (4.7 +/- 4.4%) and EBAN (13 +/- 6. 5%). These
      findings revealed that drastic changes in the morphology of erythroblasts were
      characteristic features of MDS, and may reflect a disturbance in
      kinetochore/spindle microtubules, such as endoreduplication, c-mitosis or
      restitution, in addition to chromosome lagging.

PMID- 10085437
TI  - Responses to single-dose thrombopoietin decrease with higher platelet counts in
      mice.
AB  - Since the description of human thrombopoietin (TPO) we investigated the
      thrombocytosis-inducing capacity of human serum samples derived from individuals
      with altered thrombocytopoiesis. Several times the degree of thrombocytosis
      developing in recipient mice differed markedly even when applying the same human
      material. In the last 2 years, we applied single doses of recombinant human TPO
      (rHuTPO) to random-bred CFLP mice, and the same observation was made. Taken
      together with previous information (before 1970) it was possible to select cases
      in which the percent increases in circulating platelet counts inversely
      correlated with the starting levels. It appears, however, that apart from the
      known absorbing role of platelets and megakaryocytes, the response to single
      doses of exogenous rHuTPO in mice depends, at least partially, on an unknown
      endogenous homeostatic mechanism. Mixing thrombopoietically active human sera
      with platelet-free normal serum in a 1:1 ratio remarkably reduced the
      thrombocytosis-inducing capacity. Repeated pharmacological doses of TPO, applied
      in the majority of the reported trials, however, easily obscure the physiological
      control mechanism.

PMID- 10085438
TI  - Clinical outcome in three patients with myelodysplastic syndrome showing
      polyclonal hematopoiesis.
AB  - The clinical outcome of 3 myelodysplastic syndrome (MDS) patients with polyclonal
      hematopoiesis is reported. All patients were heterozygous for the
      phosphoglycerate kinase (PGK) gene. The presence of polyclonal hematopoiesis was
      determined by the X-chromosome-linked restriction fragment length polymorphism
      methylation method using the PGK gene as a marker. The patients were initially
      diagnosed as having refractory anemia (RA), RA with ring sideroblasts (RARS), and
      RA with an excess of blasts (RAEB), respectively. Their pancytopenia persisted
      during the follow-up period of 11.4 years for the RA patient, 19.5 years for the
      RARS patient and 0.8 years for the RAEB patient. Although the RARS patient
      continues to be in good health, leukemic transformation occurred in the other 2
      patients. A karyotype change from 46,XX to 45,XX,t(3;21),-7 was observed at the
      time of disease progression in the RA patient. The coexistence of a monoclonal
      MDS clone and normal bone marrow cells is thought to be the most probable reason
      for the polyclonal hematopoiesis of these patients.

PMID- 10085439
TI  - Spontaneous remission of anemia associated with a myelodysplastic syndrome with
      disease evolution into a myeloproliferative state.
AB  - A red cell transfusion-dependent patient with a myelodysplastic syndrome had
      progression into a myeloproliferative state with thrombocytosis. At the same
      time, the patient became transfusion independent, and a subsequent bone marrow
      examination revealed a previously undetected loss of chromosome 7. The patient
      remains well with control of thrombocytosis by anagrelide therapy.

PMID- 10085440
TI  - Anti-activated factor X profiles in pregnant women receiving antenatal
      thromboprophylaxis with enoxaparin.

PMID- 10085441
TI  - Oral and intravenous itraconazole for systemic fungal infections in neutropenic
      haematological patients: meeting report. London, United Kingdom, 20 June 1998.
AB  - Effective prevention, or treatment, of invasive fungal infection in the
      neutropenic patient has hitherto been unsatisfactory because of either an
      inadequate anti-fungal spectrum of the agent or important toxicity. Itraconazole
      is effective against a broad spectrum of the opportunistic pathogens seen in
      Europe and North America. Prior problems with absorption, e.g. in the marrow
      transplant recipient, have been overcome with the introduction of an oral
      solution and an i.v. preparation. The deliberations of an expert meeting held in
      June, 1998 include recommendations on which patient requires one of these new
      preparations based on clinical trials, the dose and route. Important drug
      interactions are also detailed.

PMID- 10085442
TI  - Combination ACE inhibitor and angiotensin II receptor antagonist therapy in
      diabetic nephropathy.
AB  - The benefit of angiotensin-converting enzyme (ACE) inhibitor (i) therapy in
      diabetic glomerulosclerosis is thought to be largely the result of attenuation of
      angiotensin II (AngII) effects on blood pressure, glomerular hemodynamics and
      hypertrophy, and tissue fibrosis. The present study was undertaken to determine
      whether the addition of AngII receptor antagonist therapy to ACEi therapy in
      diabetic nephropathy results in attenuation of AngII effects beyond that achieved
      by ACEi therapy alone. Seven patients were studied as inpatients on the General
      Clinical Research Center each for 3 consecutive weeks as follows: week 1, the
      patients' usual regimen which included daily oral moderate to high dose ACEi
      therapy; week 2, the patients' usual regimen plus oral losartan (an antagonist
      (a) of the angiotensin type 1 receptor, AT1) 50 mg (n = 3) or 100 mg (n = 4)
      daily; week 3, return to the patients' usual regimen. Diet, physical activity,
      and blood glucose were held as constant as possible during the three weeks of
      daily testing. We found that plasma renin levels increased significantly during
      combination therapy and then returned to baseline values with discontinuation of
      AT1a therapy: mean baseline renin values (week 1) 3.0 ng/ml/min +/- 1.1 SE, mean
      renin values during combination therapy (week 2) 7.0 ng/ml/min +/- 3.2 (p =
      0.0078 by Wilcoxon rank sum test), mean renin values after discontinuation of
      AT1a therapy (week 3) 3.9 ng/ml/min +/- 2.0 (NS compared to baseline values). In
      addition, 2 patients developed transient hypotension when losartan therapy was
      initiated. During this short-term study, 24-hour proteinuria, serum creatinine,
      serum potassium, and plasma aldosterone were not changed significantly by
      combination therapy. We conclude that in patients with diabetic nephropathy
      addition of AT1a therapy to ACEi therapy attenuates AngII effects better than
      ACEi therapy alone. We suggest that combination therapy for the management of
      diabetic glomerulosclerosis merits further investigation.

PMID- 10085443
TI  - Biochemical parameters, nutritional status and efficiency of dialysis in CAPD and
      CCPD patients.
AB  - BACKGROUND/AIMS: Several studies indicate that small solute transport is
      influenced by peritoneal dialysate volume and dwell time. This study focuses on
      the clinical impact of peritoneal dialysis modality, continuous ambulatory
      peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD).
      METHODS: We studied 18 patients on CAPD and 11 on CCPD for 18 months and assessed
      biochemical parameters, nutritional status and efficiency of dialysis at 6-month
      intervals. RESULTS: Four-hour D/P urea and creatinine ratios were similar in both
      CAPD and CCPD patients. However, 24-hour D/P urea and creatinine ratios were
      significantly higher in CAPD than in CCPD patients (0.9 +/- 0.1 vs. 0.8 +/- 0.2
      and 0.8 +/- 0.1 vs. 0.6 +/- 0.2, p < 0.05 and p < 0.01, respectively). The
      dialysate urea nitrogen concentration was significantly different between the two
      groups (65 +/- 14 mg/dl in CAPD, 48 +/- 13 mg/dl in CCPD; p < 0.05). Total weekly
      Kt/V and total weekly creatinine clearance were not significantly different
      between CAPD and CCPD patients at 18 months (1.6 +/- 0.4 vs. 1.7 +/- 0.3 and 52
      +/- 21 vs. 50 +/- 12 liters, respectively). Two-way ANOVA with a post-hoc
      Bonferroni-Dunn test showed serum potassium concentration was significantly lower
      in CCPD patients at 18 months (3.8 +/- 0.5 mEq/l, p < 0.05), and significant
      increases in triglyceride levels in the CAPD groups by 18 months (301 +/- 286
      mg/dl, p < 0.05). CONCLUSION: This study demonstrates that the mean serum
      triglyceride level increases in CAPD patients over time, and the mean serum
      potassium concentration decreases in CCPD patients at 18 months. Dialysis
      adequacy and nutritional status are not significantly different between the two
      peritoneal dialysis modalities, CAPD and CCPD. We suggest the peritoneal dialysis
      prescription for CAPD or CCPD with respect to volume and frequency of exchanges
      be individualized to achieve adequate of therapy.

PMID- 10085444
TI  - Prevalence of microalbuminuria and relationship to the risk of cardiovascular
      disease in the Japanese population.
AB  - The prevalence of microalbuminuria and its relationship to cardiovascular disease
      risk factors were examined in subjects participating in an annual physical and
      laboratory examination program. The urinary albumin concentration and the urinary
      albumin/creatinine ratio were determined in morning urine specimens. A
      turbidimetric immunoassay was used for the measurement of urinary albumin. Of the
      731 subjects, 41 (5.6%) who were weakly positive or positive on a routine
      dipstick test for protein were excluded from the final analysis of data.
      Microalbuminuria was present in 14.5% of the men, in 12.4% of the women, and in
      13.2% of the entire subject population when defined as a urinary albumin
      concentration of 30-299 microgram/ml. The prevalence of microalbuminuria was
      significantly higher in subjects with a high normal blood pressure (15.0%) or
      hypertension (26.2%) as compared with normotensive subjects (6.5%). Subjects with
      impaired glucose tolerance (24.3%) or hyperglycemic subjects (50.0%) had a
      significantly higher prevalence of microalbuminuria than normoglycemic subjects
      (11.3%). The prevalence of microalbuminuria was significantly higher in subjects
      with left ventricular hypertrophy (47.1%) as compared with those with normal
      electrocardiograms (11.3%). A good correlation was observed between urinary
      albumin concentration and albumin/creatinine ratio, and both showed a significant
      positive correlation with age, systolic and diastolic blood pressures, and
      fasting plasma glucose, total serum protein, albumin, and triglyceride levels,
      but not with angiotensin-converting enzyme activity. Multiple regression analysis
      demonstrated that both the urinary albumin concentration and the
      albumin/creatinine ratio show a significant positive correlation with systolic
      blood pressure and fasting plasma glucose. The prevalence of microalbuminuria was
      about 13% in this Japanese cohort, and the systolic blood pressure and the
      fasting plasma glucose level were demonstrated as independent risk indicators for
      both urinary microalbumin level and urinary microalbumin/creatinine ratio.

PMID- 10085445
TI  - Interleukin-4 cooperates with interleukin-10 to inhibit vascular permeability
      factor release by peripheral blood mononuclear cells from patients with minimal
      change nephrotic syndrome.
AB  - Increased production of a vascular permeability factor (VPF) from peripheral
      blood mononuclear cells (PBMC) in patients with minimal-change nephrotic syndrome
      (MCNS) has been reported. Interleukin-4 (IL-4) and interleukin-10 (IL-10), both
      produced by T-helper type-2 cells, are cytokines with the capacity to
      downregulate proinflammatory responses. To gain insight into the immunoregulatory
      properties of these cytokines, we analyzed the effects of recombinant human IL-4
      and IL-10 on VPF release in MCNS patients. In the present study we show that the
      regulatory cytokines IL-4 and IL-10 are potent inhibitors of the VPF activity of
      concanavalin A-activated MCNS PBMC. Each cytokine was found to suppress VPF
      release in a dose-dependent manner. Moreover, when used at suboptimal
      concentrations, a combination of the two cytokines resulted in enhanced
      suppression of VPF release. Neutralization of endogenously produced IL-4 and IL
      10 by both anti-IL-4 and anti-IL-10 antibodies resulted in an increased release
      of VPF. These data demonstrate that IL-4 acts in concert with IL-10 to inhibit
      VPF release and suggest that they are effective biologic regulators of the VPF
      responses in vitro.

PMID- 10085446
TI  - Plasma immunoreactive leptin and neuropeptide Y levels in kidney transplant
      patients.
AB  - Leptin and neuropeptide Y (NPY) seem to play an important role in food intake and
      energy expenditure. Leptin is secreted by adipose tissue in proportion fo fat
      stores and is presumed to be an important anorectic hormone. NPY is produced by
      the hypothalamus, and in contrast to leptin, is one of the most potent appetite
      stimulants yet demonstrated. On the other hand, in most patients increased
      appetite is present after successful kidney transplantation. Finally, a
      stimulatory effect of glucocorticoids on leptin secretion was reported. The
      present study aimed to assess the relationship between plasma leptin and NPY
      levels and body mass index (BMI) in haemodialyzed patients (HDP) with chronic
      renal failure and in kidney transplant patients (KTP). In both groups, BMI was of
      the same magnitude as in healthy controls. Despite the presence of a normal BMI,
      leptin levels in KTP (25.2 +/- 3.6 ng/ml) and in HDP with chronic renal failure
      (25.3 +/- 4.2 ng/ml) were higher than in controls (11.7 +/- 1.8 ng/ml). The mean
      plasma NPY level in KTP (168.0 +/- 10.3 pg/ml) was significantly higher (p < 0.
      01) than in controls (70.7 +/- 5.9 pg/ml) and in HDP (77.0 +/- 5.7 pg/ml). In all
      examined groups, a significant positive correlation was found between leptinaemia
      and BMI. CONCLUSIONS: (1) KTP are characterized by significantly elevated
      leptinaemia in spite of a normal BMI. In KTP this increased leptinaemia does not
      seem to be dependent only upon the fat mass and the kind and dosis of
      immunosuppressive therapy. (2) Similarly to healthy subjects, female KTP and HDP
      show markedly higher leptinaemia than males. (3) In contrast to healthy subjects
      and HDP, KTP are characterized by significantly elevated plasma NPY levels.

PMID- 10085447
TI  - Tuberculosis in active dialysis patients in Jeddah.
AB  - The incidence of tuberculosis in The Kingdom of Saudi Arabia remains high. The
      objective of this study is to determine the prevalence of Tuberculosis among
      haemodialysis patients, since they are highly susceptible to this infection. A
      retrospective study, over a 5-year period, was carried out in the Renal Units of
      two large hospitals in Jeddah. Diagnosis was established by Ziehl Neelsen
      microscopy and culture of specimens on Lowenstein-Jensen media, radiological and
      histological examinations. Tuberculosis was diagnosed in 17 of 210 patients on
      hemodialysis. Pulmonary tuberculosis was present in 10 cases and tuberculous
      lymphadenitis in 8 cases. One patient had both pulmonary and lymph node
      involvement while another one had both pulmonary and peritoneal tuberculosis.
      Mycobacterium tuberculosis was diagnosed in sputum in 5 cases, by lymph node
      histopathology in 5 cases, and combined radiological and clinical evidence in the
      remaining patients. The Mantoux test was positive in 9 (60%) cases. Eight
      patients were diabetics (47%) and there appears to be some association of
      tuberculosis with diabetes in patients on dialysis. Treatment with first-line
      anti-tuberculosis agents was continued for 6-18 months. Fourteen (82%) patients
      were completely cured while 3 showed clinical improvement only. The study showed
      that successful therapy of tuberculosis in this group of dialysis patients could
      be achieved but high index of suspicion is required to recognize the unusual
      presentation in this group of patients so that early diagnosis can be achieved
      and prompt treatment instituted. Diabetic patients presenting for dialysis, in
      areas with high endemicity for tuberculosis, chemoprophylaxis with anti
      tuberculosis agents should be considered.

PMID- 10085448
TI  - Efficacy of percutaneous transluminal coronary angioplasty for patients on
      hemodialysis. Comparison with those not on dialysis.
AB  - Ischemic heart disease has become more important in regard to mortality in
      hemodialysis (HD) patients. We examined the therapeutic outcome of initial
      percutaneous transluminal angioplasty (PTCA) in maintenance HD patients with
      angina pectoris. They consisted of 8 men and 4 women with a mean age of 56.3 +/-
      8.6 years and a mean duration of HD of 4.3 +/- 4.0 years. Thirty-six non-HD
      patients treated with initial PTCA were matched for age, sex and coronary risk
      factors, and used as a control. Angiographic lesion success was confirmed by
      angiography in 21 (84%) of the 25 stenotic sites attempted and clinical success
      was obtained in 9 (75%) of the 12 HD patients, while there were 40 (78%) lesions
      successfully removed out of the 51 stenotic sites and there were 26 (72%)
      clinically successful cases out of the 36 non-HD patients, respectively. Angina
      recurred in 4 (44%) of 9 HD patients, and in 10 (38%) of 26 non-HD patients after
      successful PTCA, where the follow-up periods were 23 +/- 20 and 28 +/- 25 months,
      respectively. There was no significant difference in cumulative lesion survival
      curve between the two groups. In conclusion, PTCA for chronic HD patients is as
      effective as that for non-HD patients, at least regarding initial PTCA.

PMID- 10085449
TI  - Plasma exchange in rapidly progressive renal failure due to multiple myeloma. A
      retrospective case series.
AB  - BACKGROUND/AIMS: To evaluate the effect of plasma exchange on renal function in
      patients with rapidly progressive renal failure secondary to multiple myeloma.
      METHODS: The study was done through a retrospective chart review using a
      standardized form at a tertiary care centre in southwestern Ontario. Patients
      were included in the study if they had a diagnosis of multiple myeloma and
      rapidly progressive renal failure. Multiple myeloma was defined by a bone marrow
      aspirate >15% plasma cells plus one of the following: serum monoclonal
      paraproteins, monoclonal light-chain excretion, or lytic lesions. Patients were
      excluded if they had evidence of chronic renal failure or failed to complete
      three plasma exchanges. Twenty-six patients were reviewed; of these 24 were
      followed up to 1 year. All patients received hydration, standard chemotherapy,
      and plasma exchange. The plasma exchange volume was 50 ml/kg of 50% normal saline
      and 50% human serum albumin. Primary outcome measures included (1) prevention of
      acute dialysis and (2) prevention of progression from acute to chronic dialysis;
      secondary end points included (1) a decrease in creatinine of 25% or more within
      3 months of the last plasma exchange and (2) survival at 1 year. RESULTS: Sixteen
      of 24 patients, followed up to 1 year, did not require dialysis. Two patients
      required dialysis initially, but were able to come off dialysis after 3 months.
      Fourteen patients were alive at 1 year, 13 of whom were dialysis independent.
      Twelve of 13 dialysis-independent patients had a >25% reduction in creatinine at
      3 months. Two patients were lost to follow-up after discharge and were not
      included in the analysis. CONCLUSIONS: This retrospective study suggests that
      plasma exchange may offer some benefit in preventing the initiation or
      continuation of dialysis in patients with rapidly progressive renal failure
      secondary to multiple myeloma. A randomized controlled prospective study is
      needed to determine whether plasma exchange should be recommended as a standard
      treatment for patients with rapidly progressive renal failure due to multiple
      myeloma.

PMID- 10085450
TI  - Percutaneous cuffed catheter insertion by nephrologists.
AB  - The use of Dacron cuff double-lumen permanent catheters for hemodialysis has
      become more common in the dialysis unit as patients await for creation or
      maturation of a permanent hemoaccess for various reasons. Placement of these
      catheters is often done by surgeons. Nephrologists skilled in the placement of
      temporary central vein accesses can extend their skill to placement of cuff
      catheters with the current available peel-away insertion technique. Data are
      presented on the percutaneous placement of 77 Dacron cuff permanent catheters by
      4 nephrologists in two medical centers in a nonoperating room setting with
      minimal complications.

PMID- 10085451
TI  - Living-related-donor kidney transplantation outcome in recipients with primary
      focal-segmental glomerulosclerosis.
AB  - We studied the outcome of renal transplantation in 30 patients with primary focal
      segmental glomerulosclerosis (FSGS) and in 30 controls in whom renal failure was
      secondary to nonglomerular renal diseases. All patients received living-related
      donor kidneys, and the majority had one-haplotype HLA matching. Within the follow
      up period, the mean serum creatinine values were significantly higher in FSGS
      recipients as compared with the control group (p = 0.02). However, the frequency
      of acute rejection episodes and the mean blood pressure values were not
      significantly different between the two groups. There was a tendency of a higher
      incidence of proteinuria among FSGS recipients in comparison with the controls.
      Moreover, nephrotic-range proteinuria occurred only in 3 recipients of the FSGS
      group. Recurrence of FSGS was morphologically documented in 2 recipients 7 and 18
      months, respectively, after transplantation. It is concluded that FSGS as the
      primary disease has a negligible impact on the living-related-donor kidney
      transplantation in the Egyptian population. Therefore, this disease should not
      discourage transplantation for this group of patients.

PMID- 10085452
TI  - Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing
      bowel regimen.
AB  - Phosphate intoxication, manifested by hypocalcemic tetany and acute renal
      failure, may complicate bowel-cleansing preparations which contain phosphate.
      These preparations are commonly used to prepare patients for various
      gastrointestinal procedures. Often, patients who receive these regimens are at
      increased risk of phosphate intoxication from diseases which slow
      gastrointestinal transit or decrease renal excretion (renal insufficiency). We
      present a patient who developed oliguric acute renal failure from severe
      phosphate intoxication associated with a phosphate-containing bowel-cleansing
      regimen.

PMID- 10085453
TI  - Oxalate kinetics and reversal of the complications after orthotopic liver
      transplantation in a patient with primary hyperoxalosis type 1 awaiting renal
      transplantation.
AB  - We present the case of a young woman with end-stage renal disease secondary to
      primary hyperoxaluria type 1, who after 3 years and 6 months of maintenance
      hemodialysis, and despite intensification of the dialytic treatment, developed
      severe livedo reticularis in her extremities leading to ischemic cutaneous
      ulcerations, necessitating continuous intravenous infusion of narcotics for pain
      control. She received a liver transplant after native hepatectomy. However, due
      to positive crossmatch, she could not receive a kidney from that donor. After
      transplantation, following serial serum oxalate levels, the hemodialysis regimen
      was safely reduced from 4 h daily to 3 h three times weekly. Over the course of 6
      weeks after liver transplantation, her livedo reticularis resolved, the ischemic
      ulcers markedly improved, she was weaned off all pain medications, and her
      erythropoietin-resistant anemia resolved. Our results suggest that in patients
      with primary hyperoxaluria type 1, who have received a liver transplant and are
      on maintenance hemodialysis, after serial serum oxalate determinations, some may
      safely be changed to a thrice-weekly maintenance hemodialysis regimen. Moreover,
      with this regimen the complications of systemic oxalosis can reverse.

PMID- 10085454
TI  - Nephrotic syndrome with mesangial proliferative glomerulonephritis induced by
      multiple wasp stings.
AB  - We report the case of a young male who developed severe nephrotic syndrome within
      2-3 weeks after being stung by 3 wasps. A percutaneous kidney biopsy specimen
      revealed mesangioproliferative glomerulonephritis with occasional subepithelial
      deposits suggestive of early membranous nephropathy. The patient was treated with
      oral prednisone 60 mg/day with no significant clinical response after 4 weeks, at
      which point he was started on oral cyclophosphamide, 100 mg/day, while the
      prednisone dose was tapered to 20 mg every other day over a 2-week period. Six
      months after initiation of cyclophosphamide, he still has severe nephrotic
      syndrome. We also briefly review the literature on Hymenoptera sting associated
      nephrotic syndrome.

PMID- 10085455
TI  - Nephrotic mice (ICGN strain): a model of diffuse mesangial sclerosis in infantile
      nephrotic syndrome.
AB  - The ICGN mouse strain is a unique model for naturally occurring nephrotic
      syndrome. In the present study, we examined the onset of the clinical
      manifestation of nephrotic syndrome and determined the sequence of
      intraglomerular events associated with progression of nephrotic conditions.
      Laboratory analysis revealed that homozygous (nep/nep) mice showed urinary
      albumin excretion during the suckling stage, rapidly leading to hypoalbuminemia
      accompanied by body growth failure. Renal pathology demonstrated that an initial
      intraglomerular event in the nephrotic mice was observed 3 weeks after birth in
      the form of mesangiolytic lesions, characterized by microaneurysm, platelet
      accumulation and capillary ballooning. In 6-week-old homozygous mice, mesangial
      sclerosis, characterized by mesangial expansion and glomerular hypertrophy, was
      observed in a diffuse fashion. Immunohistochemistry revealed that the glomerular
      cells in the 3-week-old homozygous suckling mice were positive for alpha-smooth
      muscle actin, suggesting a phenotypic change in the mesangial cells. Mesangial
      expansion, confirmed by the over-deposition of type I collagen, was evident until
      6 weeks after weaning, while it was of interest that fibrogenic cytokines such as
      platelet-derived growth factor and transforming growth factor-beta were not
      detected in the sclerotic glomeruli throughout the observations. Furthermore, the
      nephrotic features were shown to be resistant to steroid therapy with a high dose
      of prednisolone. Our results suggest that diffuse mesangial sclerosis, a
      hereditary glomerular disease, may be genetically generated through early
      myofibroblast formation, which occurs and develops probably independently of up
      regulation of these fibrogenic cytokines. In conclusion, the homozygous nephrotic
      mouse (ICGN strain) is believed to be a good model for investigating not only
      nephrotic conditions but also cellular and molecular pathogenesis of diffuse
      mesangial sclerosis in steroid-resistant infantile nephrotic syndrome.

PMID- 10085456
TI  - The concept of 'glomerulonephritis'. the fascinating history of evolution and
      emergence of a specialist's nosology focus on Italy and Torino.
AB  - Though the term 'nephritis' first appeared in the 19th century, this word did not
      bear the same meaning as it does today; indeed, for many years it was used to
      indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense.
      This review summarizes the long gestation of the concept of 'glomerulonephritis'
      from the prehistory of medicine up to the beginning of the second half of the
      20th century with emphasis on Italy and, in particular, on Torino, which was the
      capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge,
      this is the first study reporting an epidemiology survey of Bright's disease in
      Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease
      accounted for 26 deaths/year/10(5) population (in comparison with more than 200
      from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the
      beginning of the 20th century, Bright's disease was the seventh cause of death
      (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere,
      autopsy studies showed a higher percentage of deaths attributed to Bright's
      disease (5-7%) in comparison with those obtained from vital statistics. In 1960,
      just before the beginning of renal replacement therapy, Bright's disease
      accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly
      paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of
      deaths). Probably, it was difficult to recognize the real incidence of chronic
      renal diseases leading to death in the 1960s, and vital statistics were able to
      furnish only approximate estimates. However, noteworthy is the fact that these
      values were very close to those estimated as being the annual need for renal
      replacement therapy (10-20 cases/year/10(5) population).

PMID- 10085457
TI  - Melatonin receptors and signal transduction mechanisms.
AB  - The ovine pars tuberalis (PT) still offers the best model for the study of signal
      transduction pathways regulated by the melatonin receptor. From the evidence
      accumulated so far, it seems likely that the cAMP signal transduction pathway
      will be a major effector of a stimulatory signal to the PT which can be regulated
      by melatonin. Thus a principal action of melatonin in the PT may be the
      repression of biochemical processes driven by cAMP. However, through the
      phenomenon of sensitization, melatonin may also act to amplify a stimulatory
      input to the cAMP signal transduction pathway in the PT. These events are
      mediated via the melatonin receptor, which is itself a target for regulation by
      the melatonin signal. Studies using the PT have identified several signalling
      pathways that may serve to positively or negatively regulate the expression of
      the melatonin receptor. These and other studies in the PT have alluded to cAMP
      independent pathways regulated by the melatonin receptor.

PMID- 10085458
TI  - Structure-affinity relationships of indole-based melatonin analogs.
AB  - This paper reviews our progress made in characterizing structure-affinity
      relationships of indole-based melatonin analogs. Evidence is presented suggesting
      a preferred folded conformation for the amido side chain, almost orthogonal to
      the plane of indole. A 3D-QSAR comparative molecular field analysis (CoMFA)
      model, accounting for the observed differences in binding affinity within
      different classes of melatonergic ligands, and capable of quantitatively
      predicting the binding affinity of new compounds, is also reported.

PMID- 10085459
TI  - Indole melatonin agonists and antagonists derived by shifting the melatonin side
      chain from the C-3 to the N-1 or to the C-2 indole position.
AB  - This article reviews our efforts in the development of indole melatonin (MLT)
      agonist and antagonist compounds. Evidence is presented which indicates that high
      affinity melatonergic agonists were obtained by shifting the MLT amido side chain
      from the C-3 to the N-1 indole position. Conversely, by moving the side chain
      from the C-3 to the C-2 indole position it is possible to produce MLT antagonist
      compounds.

PMID- 10085460
TI  - Methods for the evaluation of drug action at the human melatonin receptor
      subtypes.
AB  - NIH3T3 fibroblast cells transfected with the full-length coding regions of the
      mt1 and MT2 human melatonin receptors stably expressed the receptor, coupled to a
      pertussis-toxin-sensitive G protein and exhibiting high affinity for melatonin.
      Both mt1 and MT2 melatonin receptors mediated the incorporation of [35S]GTPgammaS
      into isolated membranes via receptor-catalyzed exchange of [35S]GTPgammaS for
      GDP. The relative intrinsic activity and potency of the compounds were
      subsequently studied by using [35S]GTPgammaS incorporation. The order of potency
      was equal to the order of apparent affinity. Melatonin and full agonists
      increased [35S]GTPgammaS binding. Luzindole did not increase basal [35S]GTPgammaS
      binding but competitively inhibited melatonin-stimulated [35S]GTPgammaS binding,
      thus exhibiting antagonist action. Two other mt1 antagonists, 4P-PDOT and N-[(2
      phenyl-1H-indol-3-yl)ethyl]cyclobutanecarboxamide, behaved as partial agonists at
      the MT2 subtype, with relative intrinsic activities of 0.37 and 0.39,
      respectively. For the first time, these findings show important differences in
      analogue intrinsic activity between the human mt1 and MT2 melatonin receptor
      subtypes.

PMID- 10085461
TI  - Melatonin as a time-meaningful signal in circadian organization of immune
      response.
AB  - Melatonin is synthesized and secreted during the dark period of the light/dark
      cycle. The rhythmic nocturnal melatonin secretion is directly generated by the
      circadian clock, located within the suprachiasmatic nuclei in mammals and is
      entrained to a 24-hour period by the light-dark cycle. The periodic secretion of
      melatonin may be used as a circadian mediator to any system that can 'read' the
      message. Melatonin seems to act as an arm of the circadian clock, giving a time
      related signal to a number of body functions; one of these, the circadian
      organization of the defense of the organism, is discussed in some detail as an
      example.

PMID- 10085462
TI  - New actions of melatonin on tumor metabolism and growth.
AB  - Melatonin is an important inhibitor of cancer growth promotion while the
      essential polyunsaturated fatty acid, linoleic acid is an important promoter of
      cancer progression. Following its rapid uptake by tumor tissue, linoleic acid is
      oxidized via a lipoxygenase to the growth-signaling molecule, 13
      hydroxyoctadecadienoic acid (13-HODE) which stimulates epidermal growth factor
      (EGF)-dependent mitogenesis. The uptake of plasma linoleic acid and its
      metabolism to 13-HODE by rat hepatoma 7288CTC, which expresses both fatty acid
      transport protein and melatonin receptors, is inhibited by melatonin in a
      circadian-dependent manner. This inhibitory effect of melatonin is reversible
      with either pertussis toxin, forskolin or cAMP. While melatonin inhibits tumor
      linoleic acid uptake, metabolism and growth, pinealectomy or constant light
      exposure stimulates these processes. Thus, melatonin and linoleic acid represent
      two important environmental signals that interact in a unique manner to regulate
      tumor progression and ultimately the host-cancer balance.

PMID- 10085463
TI  - The oxidant/antioxidant network: role of melatonin.
AB  - Melatonin is now known to be a multifaceted free radical scavenger and
      antioxidant. It detoxifies a variety of free radicals and reactive oxygen
      intermediates including the hydroxyl radical, peroxynitrite anion, singlet oxygen
      and nitric oxide. Additionally, it reportedly stimulates several antioxidative
      enzymes including glutathione peroxidase, glutathione reductase, glucose-6
      phosphate dehydrogenase and superoxide dismutase; conversely, it inhibits a
      prooxidative enzyme, nitric oxide synthase. Melatonin also crosses all
      morphophysiological barriers, e.g., the blood-brain barrier, placenta, and
      distributes throughout the cell; these features increase the efficacy of
      melatonin as an antioxidant. Melatonin has been shown to markedly protect both
      membrane lipids and nuclear DNA from oxidative damage. In every experimental
      model in which melatonin has been tested, it has been found to resist
      macromolecular damage and the associated dysfunction associated with free
      radicals.

PMID- 10085464
TI  - Effects of near-ultraviolet (UV-A) light on melatonin biosynthesis in vertebrate
      pineal gland.
AB  - The effects of near-ultraviolet (UV-A) irradiation on nocturnal activity of
      serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin
      biosynthesis) in the pineal gland of the rat and chick were investigated.
      Exposure of the animals to UV-A during the 4th or 5th hour of the dark phase of
      the 12:12 h light-dark (LD) cycle suppressed the night-driven NAT activity in a
      time-dependent manner, the effects being generally more pronounced in rats than
      in chicks. The UV-A-evoked suppression of the nocturnal NAT activity was
      completely restored within 2 h (chicks) or 3 h (rats) in animals which, after
      irradiation, were returned to darkness. When a short UV-A pulse was applied to
      the animals after midnight, it induced a decrease in the enzyme activity in both
      species; yet, the effect was readily reversible only in chicks. The results
      presented here, as well as other data, demonstrate that UV-A light is a powerful
      signal affecting the pineal melatonin-generating system both in mammals and
      avians, and that the involved mechanisms may differ in the tested species.

PMID- 10085465
TI  - Cyclic 3-hydroxymelatonin: a melatonin metabolite generated as a result of
      hydroxyl radical scavenging.
AB  - The pineal secretory product, melatonin, is a potent, endogenous hydroxyl radical
      (HO.) scavenger. When melatonin was incubated in different in vitro cell-free HO.
      generating systems, a novel melatonin adduct was formed. The molecular weight of
      this new compound is 248. Its structure was found to be cyclic 3-hydroxymelatonin
      (3-OHM). A proposed reaction pathway suggests that 3-OHM is the footprint product
      of the interaction between melatonin with HO. 3-OHM was also detected in the
      urine of both rats and humans. This urinary metabolite is identical to the
      compound generated in the in vitro chemical reaction between HO. and melatonin.
      This provides direct evidence that melatonin, under physiological conditions,
      functions as an antioxidant to detoxify the most reactive and cytotoxic
      endogenous HO. When exogenous melatonin was administered to young rats, urinary 3
      OHM levels increased significantly in the treated rats compared to those in
      controls. This indicates that even in young animals there is insufficient
      endogenously produced melatonin to detoxify the basal levels of the toxic HO. The
      accumulated damage induced by the escaped HO. that results when the HO. avoids
      detoxification over the course of a life time may directly or indirectly
      accelerate aging and aging-related diseases.

PMID- 10085466
TI  - Antiproliferative effects of melatonin and CGP 52608.
AB  - The antiproliferative effects of melatonin and CGP 52608, an exogenous ligand for
      RZR/ROR receptors, are compared in the present paper. Both compounds exerted
      similar inhibitory effects on the proliferation of neoplastic cells in mouse
      colonic adenocarcinoma, DU 145 human prostate cancer, MCF-7 human breast
      carcinoma, and rat diethylstilbestrol-induced prolactinoma. Although it has been
      suggested that melatonin may influence the proliferation of tumor cells via
      RZR/ROR receptors, it cannot be excluded that the antiproliferative effects of
      melatonin and CGP 52608 are unrelated and mediated by different intracellular
      mechanisms.

PMID- 10085467
TI  - The dim light melatonin onset, melatonin assays and biological rhythm research in
      humans.
AB  - The most useful marker for human circadian phase position is the dim light
      melatonin onset (DLMO). This is optimally obtained by sampling blood or saliva in
      the evening at intervals of 30 min or less. Ambient light intensity should not
      exceed 30-50 lx. For many years, the DLMO was determined mainly with the 'gold
      standard' GCMS technique for measuring melatonin in human plasma. However, new
      and improved RIAs now provide the requisite sensitivity and accuracy
      (specificity) for detecting the time that low daytime levels begin to increase in
      the evening: the lower the operational threshold for the DLMO, the more reliable
      it is as a phase marker.

PMID- 10085468
TI  - The use of melatonin for the treatment of insomnia.
AB  - The pineal product melatonin is involved in the regulation of the sleep/wake
      cycle in humans. In blind individuals and in people travelling through time
      zones, melatonin rhythms are sometimes unsynchronized with the diel cycle, and
      nocturnal sleep may be disturbed. Low or distorted melatonin rhythms have
      repeatedly been reported in middle aged and elderly insomniacs. Melatonin
      administration effectively synchronized the sleep wake cycle in blind individuals
      and in subjects suffering from jet lag and advanced sleep onset in subjects
      suffering from delayed sleep phase syndrome. In elderly insomniacs, melatonin
      replacement therapy significantly decreased sleep latency, and/or increased sleep
      efficiency and decreased wake time after sleep onset. In addition, melatonin
      substitution facilitated benzodiazepine discontinuation in chronic users. These
      data show an association between melatonin rhythm disturbances and difficulties
      to promote or maintain sleep at night. Specific melatonin formulations may be
      useful to treat circadian-rhythm-related sleep disorders and age-related
      insomnia.

PMID- 10085469
TI  - Melatonin in circadian sleep disorders in the blind.
AB  - Assessment of sleep patterns in blind people demonstrates a high prevalence of
      sleep disorders. Our studies have shown that subjects with no conscious light
      perception (NPL) have a higher occurrence and more severe sleep disorders than
      those with some degree of light perception (LP). A detailed study of 49 blind
      individuals showed that those with NPL are likely to have free-running (FR)
      circadian rhythms (aMT6s, cortisol) including sleep. Non-24-hour (or FR) sleep
      wake disorder, characterised by periods of good and bad sleep is a condition that
      may benefit from melatonin treatment. Melatonin has been administered to NPL
      subjects with FR circadian rhythms and compared with placebo (or the no-treatment
      baseline) sleep parameters improved. The results suggest that prior knowledge of
      the subject's type of circadian rhythm, and timing of treatment in relation to
      the individual's circadian phase, may improve the efficacy of melatonin.

PMID- 10085470
TI  - A melatonin preparation with a pulsatile liberation pattern: a new form of
      melatonin in replacement therapy.
AB  - Using melatonin (MLT) as a circadian synchroniser in humans to treat rhythm
      disorders, it is desirable to have controlled-release dosage forms. Following in
      vitro liberation tests, one fast-release form containing 5 mg MLT (capsule A) and
      two oral pulsatile-dosage forms containing 10 mg MLT each (capsules B and C) were
      studied in a randomised, single-dose, threefold cross-over study in 15 healthy
      male volunteers after investigation of capsule B in dogs. Mean peak
      concentrations of MLT in serum (pmol/ml) were reached between 0.5 h and 0.75 h:
      Cmax1 20.7 (A), 16.4 (B), 9.7 (C). Capsules B and C released a second MLT pulse
      after about 3.5 h with Cmax2 of 13.0 and 17.5 pmol/ml, respectively. The time
      course of the renally excreted main metabolite 6-sulphatoxymelatonin (aMT6s)
      correlates with that of changes in MLT serum concentrations. The kinetic profile
      of the delivery system is adjusted to the pattern of sleep maintenance
      disturbances.

PMID- 10085471
TI  - Melatonin in epilepsy: first results of replacement therapy and first clinical
      results.
AB  - At a single evening dose of 5-10 mg, melatonin (MLT), the pineal gland hormone,
      can exert a positive effect on the frequency of epileptic attacks in children
      with sleep disturbances of various etiologies. We have shown that the sleep
      behavior can be normalized and an existing epilepsy can be favorably influenced.
      Pretherapeutic MLT secretion profiles can provide new information concerning the
      origin and treatment of these disturbances. In vitro experiments suggest that
      this effect might be the result of the interaction between MLT and MLT-specific
      receptors in the neocortex. Due to its favorable safety profile, MLT can be
      liberally administered in the specified doses and be considered as a useful
      antiepileptic drug.

PMID- 10085472
TI  - Melatonin influences human balance.
AB  - In order to evaluate a possible correlation between melatonin, the cerebellum
      and, consequently, human balance, a double-blind pilot study was performed in 5
      subjects with random administration of different doses of melatonin. Before and 1
      h after a single administration, a complete otoneurological examination was
      performed. This first pilot study revealed that melatonin had effects on human
      equilibrium although these effects were not dosage related and were different in
      individual subjects. On the basis of these results, a second study was performed.
      Fourteen healthy volunteers were investigated before and 1 h after administration
      of a single dose of 10 mg melatonin. The otoneurological examination was
      restricted to the evaluation of: horizontal saccades, horizontal sinusoidal
      smooth pursuit, eyes open, eyes closed and head retroflexed static posturography.
      All subjects showed a decrease in posturographic performances, especially in the
      simplest test (eyes open) and half of them (6 out of 13) showed also impairment
      of eye movements. These results confirm the role of melatonin in the control of
      sensorimotor performances, and the cerebellar receptors might be correlated with
      the control of human balance.

PMID- 10085473
TI  - Melatonin in psychiatric disorders - subtyping affective disorder.
AB  - Altered diurnal secretory patterns, i.e. altered phase and/or amplitude of
      melatonin have been reported in sleep and affective disorders. The alteration may
      depend on environmental factors which in vulnerable individuals may cause sleep
      and/or affective disorders. Early stress in conjunction with development of
      resistance to corticotropin-releasing hormone may be linked to the low melatonin
      syndrome in subgroups of depressed patients. Also the seasonal variation in
      melatonin as well as serotonin may be linked to the seasonal pattern seen in
      subgroups of affective disorders. Melatonin may be used as a combined marker for
      proneness to develop affective disorders especially in latent carriers of bipolar
      disorders.

PMID- 10085474
TI  - Effect of melatonin in selected populations of sleep-disturbed patients.
AB  - In an open pilot study on the efficacy of melatonin in the treatment of sleep
      disorders, patients with sleep disturbances alone, patients with sleep
      disturbances and signs of depression and patients with sleep disorders and
      dementia received 3 mg melatonin p.o. for 21 days, at bed time. After 2-3 days of
      treatment, melatonin significantly augmented sleep quality and decreased the
      number of awakening episodes in patients with sleep disturbances associated or
      not with depression. Estimates of next-day alertness improved significantly only
      in patients with primary insomnia. Agitated behavior at night (sundowning)
      decreased significantly in dementia patients. In a second retrospective study, 14
      Alzheimer's disease (AD) patients received 9 mg melatonin daily for 22-35 months.
      A significant improvement of sleep quality was found, while there were no
      significant differences between initial and final neuropsychological evaluation
      (Functional Assessment Tool for AD, Mini-Mental). The results indicate that
      melatonin can be useful to treat sleep disturbances in elderly insomniacs and AD
      patients.

PMID- 10085475
TI  - Suppression of UV-induced erythema by topical treatment with melatonin. Influence
      of the application time point.
AB  - The UV-suppressive effect of topical melatonin was assessed at different
      application time points in a double-blind randomized clinical trial. The lower
      back of 20 healthy volunteers was treated with 0.6 mg/cm2 melatonin or vehicle
      either 15 min before or 1, 30 or 240 min after UV irradiation. The erythema was
      evaluated visually and measured by chromametry 24 h after irradiation. UV
      absorbing effects of melatonin were measured at a concentration of 8 microg/ml
      with a spectrophotometer. Melatonin absorbs UV light at a wavelength of 225-275
      nm which is clearly below the wavelength of UVA and UVB (290-390 nm). The visual
      score showed that application of melatonin 15 min before irradiation
      significantly suppressed erythema compared to treatment with vehicle alone (p <
      0.001). Similar results were found by chromametry (p < 0.001). Treatment after
      irradiation showed no UV suppression. The erythema suppressive effect of
      melatonin might be explained by the radical-scavenging mechanism of quenching
      meanly hydroxyl radicals (.OH) which are known to be most present in sunburn
      reaction of the skin. The protective effect of the pre-irradiation treatment
      might be explained by penetration into the skin within 15 min and the presence in
      a local concentration at the irradiation time point.

PMID- 10085476
TI  - Protective effect of melatonin on zymosan-induced cellular damage.
AB  - We investigated whether in vivo melatonin treatment inhibits cellular injury
      induced by peroxynitrite production and PARS activation in macrophages collected
      from rats subjected to zymosan-induced shock. Macrophages harvested from the
      peritoneal cavity exhibited a significant production of peroxynitrite, as
      measured by the oxidation of the fluorescent dye dihydrorhodamine 123.
      Furthermore, zymosan-induced shock suppressed macrophage mitochondrial
      respiration, DNA strand breakage, activation of the nuclear enzyme poly(ADP
      ribose)synthetase (PARS) and reduction of cellular levels of NAD+. In vivo
      treatment with melatonin (25 and 50 mg/kg, i.p., 1 h after zymosan injection)
      significantly and dose-dependently reduced peroxynitrite formation and prevented
      the appearance of DNA damage, decrease in mitochondrial respiration, loss of
      cellular levels of NAD+ and PARS activation. Our study supports the view that the
      antioxidant and anti-inflammatoy effect of melatonin is also correlated with the
      inhibition of peroxynitrite production and PARS activation. In conclusion,
      melatonin may be a novel pharmacological approach to prevent cell injury in
      inflammation.

PMID- 10085477
TI  - Aspects of melatonin manufacturing and requirements for a reliable active
      component.
AB  - Commercially available melatonin was found to contain impurities associated with
      eosinophilia-myalgia syndrome (EMS). From sample analysis, remarkable differences
      in impurity profiles between the active ingredient from various suppliers could
      be found. An industrial process was developed which guarantees a high purity
      melatonin active ingredient. All potential impurities have been characterized and
      synthetized for analytical conformity with pharmaceutical regulations. To avoid
      any side effects from impurities, only high-purity melatonin should be utilized
      from the laboratory through to commercialization.

PMID- 10085478
TI  - Retinal structure and visual acuity in a polyprotodont marsupial, the fat-tailed
      dunnart (Sminthopsis crassicaudata).
AB  - The visual system of the fat-tailed dunnart (Sminthopsis crassicaudata), a small
      polyprotodont marsupial, has been examined both anatomically and behaviourally.
      The ganglion cell layer was examined in cresyl-violet stained wholemounts and
      found to contain a mean of 81,400 ganglion cells (SD +/- 3,360); the
      identification of ganglion cells was supported by a correspondence to optic axon
      counts. Ganglion cells were distributed as a mid-temporally situated area
      centralis, embedded in a pronounced visual streak. Localised implants of
      horseradish peroxidase into retinal wholemounts revealed both A-type and B-type
      horizontal cells. Sections of the outer retina showed it to be rod-dominated,
      with a rod-to-cone ratio of 40:1 at the area centralis; cones were found to
      contain oil droplets but double cones were not a prominent feature. The retinal
      pigment epithelium consisted of squamous cells. Visual acuity, estimated from
      counts of peak ganglion cell density (8,300/mm2, SD +/- 1,180) and measurements
      of posterior nodal distance (2.9 mm), was found to be 2.30 cycles per degree. The
      value was close to that of 2.36 cycles per degree estimated by behavioural tests
      using a Mitchell jumping stand; values were similar at low, intermediate and high
      light levels. Our findings are discussed in relation to the lifestyle of the
      dunnart.

PMID- 10085479
TI  - Retinal projections and retinal ganglion cell distribution patterns in a sturgeon
      (Acipenser transmontanus), a non-teleost actinopterygian fish.
AB  - Retinal projections in a sturgeon were studied by injecting biocytin or HRP into
      the optic nerve. The target areas are the preoptic area, thalamus, area
      pretectalis, nucleus of posterior commissure, optic tectum, and nuclei of the
      accessory optic tract. Furthermore, a few labeled fibers and terminals were found
      in a ventrolateral area of the caudal telencephalon. All retinal projections are
      bilateral, although contralateral projections were more heavily labeled.
      Retrogradely labeled neurons were found in the ventral thalamus bilaterally.
      Retinal projections in sturgeons are similar to those of other non-teleost
      actinopterygians and chondrichthyans (sharks), in terms of the targets and extent
      of bilateral projections. Distribution patterns of ganglion cells in the retina
      were examined in Nissl-stained retinal whole mount preparations. The highest
      density areas were found in the temporal and nasal retinas, and a dense band of
      ganglion cells was observed along the horizontal axis between the nasal and
      temporal areas of highest density. The density of ganglion cells in the dorsal
      retina is the lowest. The total number of ganglion cells was estimated to be
      about 5 x 10(4) in a retina. The existence of a low density area in the dorsal
      retina suggests reduced visual acuity in the ventral visual field.

PMID- 10085480
TI  - Tectal fiber connections in a non-teleost actinopterygian fish, the sturgeon
      Acipenser.
AB  - Tectal fiber connections were studied in members of an early branch of the
      actinopterygian lineage, the sturgeons Acipenser transmontanus and A. schrenkii,
      by means of biocytin, HRP, biotinylated dextran amine, and DiI tract tracing
      methods. The aim of this study is to elucidate the visual pathway via the optic
      tectum to the thalamus as a part of a series of studies on the visual pathways in
      sturgeons. After biocytin or biotinylated dextran amine injections to the optic
      tectum terminals are found bilaterally in the medial and lateral portions of both
      the dorsal thalamus and ventral thalamus. Ipsilateral projections are much more
      abundant. Tectal recipient areas in the thalamus overlap in part with the retinal
      recipient areas. After HRP or DiI injections to the dorsal or ventral thalamus,
      tectal neurons projecting to the thalamus were labeled in the ipsilateral or
      bilateral stratum periventriculare. Dendritic morphology of tectothalamic neurons
      suggests that they receive direct retinal input. These results suggest that
      visual information passes through the tectum to the thalamic areas which also
      receive direct retinal projections. In this regard, the visual system of
      Acipenser resembles that of chondrichthyans (sharks). Other fiber connections of
      the tectum are also described, which have not previously been studied by tracer
      methods in a sturgeon.

PMID- 10085481
TI  - Visual thalamotelencephalic pathways in the sturgeon Acipenser, a non-teleost
      actinopterygian fish.
AB  - Terrestrial vertebrates (amphibians, reptiles, birds, and mammals) possess two
      visual systems, the geniculate and extrageniculate pathways to the telencephalon.
      In cartilaginous fishes (e.g. sharks) both retinal and tectal neurons project to
      neurons in the thalamus, which themselves project to a single area in the
      telencephalon. The condition in ray-finned fishes (Actinopterygii) is ambiguous.
      In many teleosts there is a well developed extrageniculate pathway but no obvious
      geniculate system. This study reports on the thalamotelencephalic projections of
      a sturgeon, a non-teleost ray-finned fish. Several tract tracing methods (e.g.,
      HRP, WGA-HRP, biocytin, BDA, DiI) were employed in conjunction with normal
      techniques for identifying neural structures (e.g., Nissl, Golgi). After
      injections of tracer into retinal and tectal recipient areas of the thalamus,
      labeled terminals were observed in the ventrolateral region of the caudal
      telencephalon, an area referred to as the thalamic projection area. After
      injections of tracer into the telencephalon, populations of retrogradely filled
      neurons were located in both the dorsal and ventral thalamus. These data
      demonstrate that thalamic neurons in both retinal and tectal pathways project
      directly to the telencephalon. These results support the view that two visual
      pathways are a primitive feature of vertebrate brain organization. These results
      are also consistent with the hypothesis that the ancestor of Acipenser and
      Teleostei (Actinopteri) acquired a novel visual pathway to the telencephalon
      through the ventral portion of the thalamus.

PMID- 10085482
TI  - Heart rate variability as a marker of myocardial perfusion.
AB  - RR variability (HRV), an independent predictor of death following myocardial
      infarction, may also be related to other features of coronary artery disease. We
      evaluated its ability to differentiate among sedentary patients with chest pain
      >/=45 years of age demonstrating either normal or abnormal myocardial perfusion
      with rest and exercise thallium-210 tomographic imaging. The major HRV difference
      between 48 men and 50 women with normal perfusion was a significantly higher high
      frequency power in women. No significant differences in mean HRV values were
      found between the 57 men with abnormal perfusion scans and the 48 men with normal
      perfusion. In both men and women with normal perfusion scans, duration of
      exercise was significantly related to age. In men with abnormal scans, impaired
      myocardial perfusion alters the relationship between exercise duration and age,
      and a group of individuals with diminished HRV and low levels of physical
      fitness, regardless of age, can be identified. Despite these latter selective
      findings, we conclude that HRV is not a sensitive indicator to differentiate
      patients with normal and abnormal myocardial perfusion.

PMID- 10085483
TI  - Pacemaker-related endocarditis. Report of 7 cases and review of the literature.
AB  - We report on 7 patients with pacemaker endocarditis diagnosed during the workup
      of long-standing fever. Persistent positive blood cultures and echocardiography
      led to the diagnosis in 6 patients whereas autopsy was diagnostic in another.
      Causative microorganisms were Staphylococcus epidermidis (3), Staphylococcus
      lugdunensis (1), Pseudomonas aeruginosa (1), Streptococcus bovis (1), and
      Streptococcus mitis-Streptococcus sanguis (1). Pulmonary embolism was present in
      nearly 50% of the cases, a figure clearly higher than previously reported. In all
      but 1 case the initial medical approach was not successful, and thus the pacing
      system was finally removed. None of the cases relapsed after the removal. We have
      reviewed the literature regarding pacemaker endocarditis, particularly with
      respect to treatment.

PMID- 10085484
TI  - Evidence of excess hereditary predisposition in women with angiographically
      documented coronary artery disease.
AB  - In a hospital-based case-control study including women and men with
      angiographically documented coronary artery disease (CAD) admitted to a
      university hospital during a 6-month period, we observed an excessive hereditary
      predisposition in women. Clustering of risk factors was more pronounced in women
      than in men. Thus, the results suggest that hereditary factors as well as
      multiple risk factors are essential when CAD is expressed in women.

PMID- 10085485
TI  - Aortic sinotubular atherosclerotic debris associated with cerebral embolic events
      can be identified by transthoracic echocardiography.
AB  - OBJECTIVE: To evaluate the association between the presence of aortic sinotubular
      debris (STAD) identified by transthoracic echocardiography (TTE) and embolic
      strokes. BACKGROUND: The presence of atherosclerotic debris in the ascending
      aorta or aortic arch detected by transesophageal echocardiography or epiaortic
      echocardiography has been well established to be correlated with embolic stroke
      or other thromboembolic events. No data are available on the role of TTE in
      describing aortic pathology in thromboembolic events. METHODS: We identified 60
      transthoracic echocardiographic studies from 11,275 studies, in which STAD was
      diagnosed. The charts of these patients (group 1; mean age 67 +/- 10 years) were
      reviewed and compared with those of 57 patients (group 2) without STAD, matched
      for age, gender and risk factors for advanced atherosclerosis. The results of
      brain imaging procedures, carotid duplex and coronary angiography were also
      reviewed. RESULTS: Ischemic stroke was found in 15 of group 1 (25%) and 4
      patients of group 2 (7%, odds ratio = 4.4; 95% confidence interval, 1.3-19.4, p =
      0.008). The average thickness of STAD was 0.7 +/- 0.2 cm in stroke patients and
      0.6 +/- 0.2 cm in patients without stroke (p = n.s.). STAD was associated with
      </=40% carotid artery stenosis. CONCLUSION: STAD detected by TTE is strongly
      associated with embolic strokes. Our findings expand the role of TTE in the
      evaluation of patients with embolic strokes.

PMID- 10085486
TI  - Relationship between depressed baroreflex function and exaggerated sympathetic
      response to exercise in patients with heart failure.
AB  - The relationship between impaired baroreflex sensitivity (BS) and the degree of
      sympathetic activation during exercise in patients with heart failure (HF) has
      not been studied in detail. For this purpose, we studied BS and measured plasma
      norepinephrine (NE) at rest, and during and after treadmill exercise in 15
      patients and 10 controls. HF patients showed lower BS in comparison to controls
      (3. 51 +/- 3.62 vs. 9.74 +/- 4.56 ms/mm Hg; p < 0.001), and higher levels of
      plasma NE at rest (449.3 +/- 147.1 vs. 261.1 +/- 82.48 pg/ml; p < 0.001) and
      during exercise (1,542 +/- 361.2 vs. 524.6 +/- 92.61 pg/ml; p < 0.001). BS was
      directly related to pVO2 (r = 0.62; p = 0.0008) and inversely related to NE at
      peak exercise and to the increase in NE during exercise (r = 0.59, p = 0.005, and
      r = 0.53; p = 0.0058). Thus, during exercise, a marked sympathetic activation
      exists in patients with moderate HF. The relationship between increased plasma NE
      during exercise and decreased BS suggests that impaired baroreceptor function may
      be present in sympathetic activation in HF patients.

PMID- 10085487
TI  - Prior cytomegalovirus infection does not predict clinical outcome after
      percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: A direct association between human cytomegalovirus (HCMV) infection
      and the development of restenosis after coronary angioplasty has been suggested.
      The aim of this prospective study was to evaluate the value of HCMV serology in
      predicting the clinical outcome after percutaneous transluminal coronary
      angioplasty (PTCA). METHODS AND RESULTS: 112 patients undergoing elective PTCA
      were included in the study. HCMV antibody levels were measured by ELISA. Cardiac
      events within a follow-up period of 6 months after PTCA were defined as (1)
      progression or recurrence of anginal complaints and/or a positive exercise test;
      (2) restenosis that required repeat revascularization. 73% of PTCA patients were
      seropositive for HCMV. Successful PTCA was achieved in a total of 94 patients,
      who were followed for 6 months. In 31/94 patients (33%) cardiac events occurred
      and in 15/94 (16%), this could be related to restenosis. We found no
      statistically significant difference between seropositive and negative patients
      with respect to anginal complaints or the need for revascularization. There was
      no evidence of acute reactivation, since titers of anti-HCMV antibodies did not
      increase after PTCA. CONCLUSION: This study shows that the clinical outcome after
      PTCA is not related to the HCMV serostatus of the patient. Therefore, our data do
      not support the hypothesis that serological markers of HCMV infection are of
      clinical importance for the assessment of a patient's individual risk after PTCA.
      This does not preclude a role for local reactivation of HCMV at the site of
      angioplasty.

PMID- 10085488
TI  - Heart rate behavior in children with atrial septal defect.
AB  - The aim of this study was to assess heart rate variability, a noninvasive
      parameter for studying the neurohumoral control of heart rate, in children with
      atrial septal defect. We examined five time-domain and three frequency-domain
      indices of heart rate variability determined from 24-hour Holter recordings in 20
      children, aged 3-14 years, with secundum atrial septal defect who were about to
      undergo operation. The measures were compared to normal ranges and to the
      hemodynamic data of the preoperative cardiac catheterization. Most indices of
      heart rate variability were moderately depressed in children with atrial septal
      defect. Our data revealed negative correlations between indices and the mean
      right atrial pressure and the enddiastolic right ventricular pressure,
      respectively. The study demonstrates the importance of the right ventricular
      filling pressures for the autonomic control of the heart in children with atrial
      septal defect.

PMID- 10085489
TI  - Early development of high-degree atrioventricular block in inferior acute
      myocardial infarction is predicted by a J-point/R-wave ratio above 0.5 on
      admission.
AB  - This study assessed the ability of simple clinical and electrocardiographic (ECG)
      variables routinely obtained on admission to identify patients with inferior
      myocardial infarction who are at high risk of developing high-degree
      atrioventricular (AV) block within the first 24 h of hospitalization in 205
      patients. The admission ECGs were classified into two patterns based on the J
      point to R-wave amplitude ratio: pattern 1: those with J-point/R-wave ratio <0.5;
      pattern 2: patients with J-point/R-wave ratio >/=0.5 in >/=2 inferior leads (II,
      III and aVF). High-degree AV block was found in 10.2% of the patients (21 of 205
      patients; 5 and 16% of the patients with initial patterns 1 and 2, respectively,
      p = 0.014). Multivariate logistic regression analysis revealed that the only
      variables independently associated with high-degree AV block were the initial ECG
      pattern 2 versus 1 (odds ratio, OR, 4.47, 95% confidence interval, CI, 1.18-16.9;
      p = 0.0276), age (OR 1.06, 95% CI 1.01-1.12; p = 0.0254); Killip class >1 (OR
      2.33, CI 0.83-6. 54; p = 0.1065) and thrombolytic therapy (OR 0.32, 95% CI 0.11
      0.93; p = 0.037).

PMID- 10085490
TI  - Specificity of cardiac troponin I and creatine kinase-MB isoenzyme in
      asymptomatic long-term hemodialysis patients and effect of hemodialysis on these
      cardiac markers.
AB  - OBJECTIVES: The objectives of this study were: (1) to evaluate the specificity of
      cardiac troponin I and creatine kinase-MB isoenzyme in ambulatory asymptomatic
      chronic renal failure patients on long-term hemodialysis, and (2) to evaluate the
      effect of hemodialysis on the serum levels of cardiac troponin I and creatine
      kinase-MB isoenzyme. METHODS: One hundred and forty-four consecutive ambulatory
      asymptomatic chronic renal failure patients on hemodialysis for a minimum of 1
      year were evaluated clinically. Serum cardiac troponin I and creatine kinase-MB
      isoenzyme levels were measured with specific monoclonal antibodies before and
      after dialysis using ACCESS Troponin I and ACCESS CK-MB assays. RESULTS: The
      specificity of serum cardiac troponin I was 83% with a cutoff level of 0.03
      ng/ml, which is an expected level for healthy population, but it rose to 100%
      with a cutoff level of 0.15 ng/ml, which is a reference level for patients with
      acute myocardial infarction. Twenty-four (17%) patients had borderline elevation
      in cardiac troponin I (>0.03 to <0.15 ng/ml). A history of angina pectoris was
      more common in the borderline-elevated cardiac troponin I subgroup. In 28% of the
      patients, serum creatine kinase-MB isoenzyme levels were increased with a
      specificity of 72% at a cutoff level of 4 ng/ml, which is the upper limit of
      normal, but the specificity rose to 98% by increasing the cutoff level value to
      10 ng/ml. There were no statistically significant differences in serum levels of
      cardiac troponin I and creatine kinase-MB isoenzyme before and after dialysis.
      CONCLUSIONS: Cardiac troponin I is highly specific in ambulatory asymptomatic
      chronic renal failure patients on long-term hemodialysis; borderline elevations
      in cardiac troponin I may represent microinjury to the myocardium. A serum level
      of creatine kinase-MB isoenzyme >2.5 times of the normal upper limit may be
      highly specific in this patient population. Hemodialysis per se does not
      significantly change the serum levels of cardiac troponin I and creatine kinase
      MB isoenzyme.

PMID- 10085491
TI  - Superiority of combined CK-MB and troponin I measurements for the early risk
      stratification of unselected patients presenting with acute chest pain.
AB  - BACKGROUND: Recent studies have suggested that positive troponin I tests are
      associated with an increased risk of cardiac death during short-term follow-up.
      However, it is unknown if troponin I tests alone or in addition to CK-MB
      measurements are superior to predict unfavorable outcome during long-term follow
      up. PATIENTS AND METHODS: In a prospective, double-blind study we assessed the
      prevalence and prognostic value of combined troponin I and CK-MB tests in an
      unselected cohort of patients (n = 292) admitted to the emergency department for
      acute chest discomfort. Patients were grouped according to the diagnosis on
      discharge in those with acute myocardial infarction (1), unstable angina (2), and
      noncardiac chest pain (3). Six months after enrollment, death rates were obtained
      and follow-up interviews were performed with respect to survival, recurrence of
      chest pain, and myocardial infarction. RESULTS: In patients with evidence of
      coronary heart disease, the mortality rate for abnormal troponin I and normal CK
      MB levels was 5.0%. Baseline troponin I and elevated CK-MB levels were associated
      with a mortality rate of 4.0%. However, the mortality rate was significantly
      higher (11.1%) in patients presenting with elevated troponin I and CK-MB values.
      In patients without myocardial infarction on admission, 10.5% with positive
      troponin I tests died compared to 1.6% with negative tests. The mortality rate in
      patients without myocardial infarction was 2.7% for patients with elevated CK-MB
      but normal troponin I values. In patients with both markers elevated a
      significantly higher mortality rate (16.7%) was found, representing a 6-fold
      increase in the death event rate. With the additional knowledge of troponin I
      values, it could be demonstrated that certain cases were misclassified as having
      noncardiac chest pain. At least some of the latter patients with above-normal
      values of troponin I were retrospectively to be reclassified as unstable angina.
      Acute non-Q-wave myocardial infarctions were occasionally misdiagnosed as either
      angina pectoris or nonischemic chest pain. CONCLUSIONS: Our data suggest the
      superiority of combined CK-MB and troponin I measurements in clinical practice
      for the early risk stratification of patients presenting with acute chest pain.
      In nonmyocardial infarctions, both CK-MB and troponin I convey independent
      prognostic information with regard to fatal outcome. Troponin I tests in addition
      to CK-MB measurements contribute to a lower rate of misdiagnoses.

PMID- 10085492
TI  - Are there differences among patients with inferior acute myocardial infarction
      with ST depression in leads V2 and V3 and positive versus negative T waves in
      these leads on admission?
AB  - We assessed whether there are differences among patients with inferior acute
      myocardial infarction and ST segment depression in leads V2-V3 between those with
      positive versus negative T waves on admission. We found no differences in the
      prevalence of concomitant significant left anterior descending coronary artery
      stenosis and anterior or posterior wall motion abnormalities on echocardiography
      between the two groups. Precordial ST segment depression with negative T wave may
      be the early electrocardiographic pattern of posterior infarction, reflecting ST
      segment elevation with positive T waves that would have been detected by leads
      facing the posterior wall.

PMID- 10085493
TI  - Acute myocardial infarction induced by alternating exposure to heat in a sauna
      and rapid cooling in cold water.
AB  - We describe a patient with acute myocardial infarction, which was thought to
      result from plaque rupture or thrombosis because of coronary artery spasm. The
      vasospasm was most likely induced by stimulation of the alpha-adrenergic
      receptors during alternating heat exposure during sauna bathing and rapid cooling
      during cold water bathing. This report emphasizes the dangers of rapid cooling
      after sauna bathing in patients with coronary risk factors.

PMID- 10085494
TI  - Aortic stenosis and coronary artery disease caused by alkaptonuria, a rare
      genetic metabolic syndrome.
AB  - Alkaptonuria is a rare metabolic disease in which homogentisic acid deposits
      occur in various body tissues. We present a case of alkaptonuria which resulted
      in aortic stenosis and coronary artery disease due to homogentisic acid
      deposition.

PMID- 10085495
TI  - Subacute stent thrombosis occurring more than one month after implantation for
      acute myocardial infarction. Description of two cases successfully treated with
      angioplasty and further stenting.
AB  - Two patients are described with anterior acute myocardial infarction who had a
      successful recanalization of a totally occluded left anterior descending coronary
      artery by means of primary angioplasty and stenting. Reinfarction occurred more
      than 1 month after implantation. At angiography, a totally occluded left anterior
      descending coronary artery at the site of stenting was observed and was
      effectively reopened with angioplasty and stenting in both cases. This report
      aims to emphasize that acute myocardial infarction still represents a major risk
      factor for subacute stent thrombosis and that this potentially catastrophic event
      may occur late after implantation. Potential implications for revascularization
      strategies and medical treatment are discussed.

PMID- 10085496
TI  - Qualitative research on drug use in Europe.

PMID- 10085497
TI  - Synthesis of qualitative research on drug use in the European Union: report on an
      EMCDDA project. European Monitoring Centre for Drugs and Drug Addiction.
AB  - This paper is a synthesis of the information in the report Inventory,
      Bibliography and Synthesis of Qualitative Research in the European Union which
      was co-ordinated for the European Monitoring Centre for Drugs and Drug Addiction,
      Lisbon, Portugal, by the National Addiction Centre, London, UK. It is based on
      the work of a network of qualitative researchers from the European Union. The
      report includes detailed information from each member state on current
      qualitative projects, relevant publications from the last 10 years and a
      directory of those researchers active in this area. The paper introduces the
      project, outlines its future direction and discusses what can be defined as
      'qualitative research'. Historical developments and the role of qualitative
      methodology in relation to research into drug use are examined. A summary of the
      project's findings is presented, and the relevance of qualitative research for
      policy-making is discussed. Finally, the methodology used to collect data for the
      project is described.

PMID- 10085498
TI  - The design and effectiveness of therapeutic community research in Europe: an
      overview.
AB  - An overview of the state of the art of research on the treatment services of the
      therapeutic community for drug addicts in Europe is presented. This research
      tradition has largely been fragmented and local in its implementation. There has
      been a scientific gap concerning evaluation research and the treatment services
      offered by the therapeutic community. The American research antecedents to the
      European tradition are reviewed. The essential European groups, research designs
      and results are presented for each country with something greater than an ad hoc
      study experience. The strengths and weaknesses of the research designs, results
      and organizations are critically assessed. Recommendations for future research
      are presented and referenced to specific recommendations for therapeutic
      community research coming out of an American National Institute on Drug Abuse
      Technical Review. Among the conclusions of the overview is the need for more
      qualitative phenomenological research to complement the existing quantitative
      approach.

PMID- 10085499
TI  - Therapeutic drug monitoring for methadone: scanning the horizon.
AB  - The initial assessment and subsequent monitoring of compliance in methadone
      treatment programmes are excessively reliant on the accuracy of self-report from
      opiate addicts themselves. Given the central position of methadone treatment in
      the therapeutic options currently available and with the increasing number of
      opiate addicts requiring treatment, improved methods of judging optimal methadone
      treatment are required. This paper explores the possible future options for
      assessing the adequacy of methadone prescribing from the analysis of methadone
      levels in urine, blood, hair and saliva. The particular promise of plasma
      therapeutic drug monitoring for methadone is explored, accompanied by an account
      of the state of the art at the time of writing.

PMID- 10085500
TI  - The use of lofexidine by drug dependency units in the United Kingdom.
AB  - Data were collected on 1,074 opiate detoxifications conducted with lofexidine,
      from 40 drug dependency units in the United Kingdom. 671 patients (62.5%)
      attempted a detoxification in the community, with the remainder attempting an
      inpatient detoxification. Patients completing the detoxification started on a
      mean dose of 0.8 mg/day (median 0.6 mg/day), titrating to a mean dose of 2.2
      mg/day (median 1.6 mg/day) and detoxifying in a mean of 10 days (median 10 days).
      Overall 614 patients (60.4%) successfully completed the detoxification. The most
      frequently recorded adverse events were dry mouth (5.3%), dizziness (8.5%) and
      sedation (6.6%). In conclusion, lofexidine is widely and successfully used to
      rapidly detoxify patients from a range of opiates.

PMID- 10085501
TI  - Risk factors of hypoglycemia in premature infants.
AB  - Hypoglycemia is a frequent complication of preterm birth and may lead to later
      CNS damage. The hypoglycemia incidence and the relative risk factors for the
      affected preterm infants were assessed. We examined 1,500 preterm infants (<37
      weeks of gestational age) consecutively admitted between January 1994 and
      December 1996 at the Department of Pediatrics of Padua University, and screened
      for hypoglycemia by Dextrostix within the first hour of life. Hypoglycemia was
      defined as blood glucose levels <40 mg% at Dextrostix. Among study prematures,
      35% had hypoglycemia; while the incidence was 9% at levels of Dextrostix <20 mg%.
      The relative risk for hypoglycemia (odds ratio, OR) was computed assuming a 99%
      confidence interval (CI). We found 5 risk factors for hypoglycemia: cesarean
      section (OR 2.24, CI 1.66-3.03), intrauterine malnutrition (SGA) (OR 1.65, CI
      1.08-2.53), NICU hospitalization (OR 1.45, CI 1. 09-1.93), gestational age
      between 30 and 33 weeks (OR 1.93, CI 1. 34-2.78), and twinning (OR 2.49, CI 1.77
      3.56). At levels of Dextrostix <20 mg%, 3 more risk factors were found:
      cardiopulmonary resuscitation at birth (OR 4.06, CI 2.52-6.54), neonatal
      respiratory distress syndrome (OR 2.21, CI 1.34-3.36) and gestational age between
      26 and 29 weeks (OR 2.16, CI 1.02-4.25). The identification of relative risk
      factors could be useful in improving the hypoglycemia prophylaxis, and in
      reducing related later CNS abnormalities.

PMID- 10085502
TI  - Ontogeny of clenched-hand development in trisomy 18 fetuses: A serial
      transabdominal fetoscopic observation.
AB  - Malpositioning of the fingers is a characteristic anomaly in fetuses with trisomy
      18. The defect results in part from muscle variations along the radial margin of
      forearm and hand, absence of the thenar muscles, anomalous tendons and
      attachments among the forearm groups, and fusions among the arm flexor group.
      These variations result in radial or ulnar displacement of the tendons of
      extensor digitorum and digiti minimi, with overlapping of the fourth and fifth
      fingers radially and second finger in an ulnar direction. The ontogeny of these
      changes is unknown. We performed serial transabdominal thin-gauge fetoscopy in a
      patient with increased nuchal thickening at 12 weeks of pregnancy at the time of
      genetic testing and again at 14 weeks at the time of termination of pregnancy.
      Changes in the positioning of the fingers were not apparent at 12 weeks, but were
      evident at 14 weeks. The findings were beyond the resolution of ultrasound. We
      conclude that malpositioning of the fingers in trisomy 18 occurs some time
      between 12 and 14 weeks of gestation. Noninvasive confirmation of these findings
      may be possible with new and improved ultrasound imaging capabilities or perhaps
      with three-dimensional ultrasound.

PMID- 10085503
TI  - Participation in prenatal screening tests and intentions concerning selective
      termination in Finnish maternity care.
AB  - AIMS: The study examined how prenatal screening tests are presented to women,
      factors associated with women's participation in screening, their experience of
      decision-making and intentions concerning pregnancy termination, and hospital
      data on rates of selective terminations. METHODS: Questionnaires were given to
      pregnant women visiting maternity centres in two Finnish towns in which serum
      screening was offered (n = 1,035) and in one town where midtrimester ultrasound
      screening was offered (n = 497). Response rates to the questionnaires were 88 and
      85%, respectively. Other questionnaires asking about selective terminations
      following detected fetal disorders were sent in 1993 to all public hospitals with
      obstetrics or gynaecology departments (response rate 100%). RESULTS: The serum
      screening test had usually been offered to women as a free choice, but for 22% of
      them it was presented as a routine procedure. Most women (92%) underwent serum
      screening and most (86%) found the decision to participate or not easy. In almost
      every aspect of presentation and participation studied, serum and ultrasound
      screening differed from each other. 85% of respondents to ultrasound screening
      answered that it was offered as a routine procedure. Close acquaintance with a
      person with congenital disability was negatively associated with participation in
      serum screening and with the intention to terminate pregnancy in case of a
      detected disability. 27% of women in the serum screening survey and 22% in the
      ultrasound survey declared that they would have declined pregnancy termination if
      a fetal disorder had been detected. However, according to the hospitals' data,
      only 13% of pregnancies with a serious fetal disorder detected were continued.
      CONCLUSIONS: All prenatal screening tests, including ultrasound examinations,
      require an adequate process of informed consent. Because the aim of such tests is
      to detect fetal malformations and syndromes, health care professionals should
      discuss the implications with women before they decide. Because acquaintance with
      a disabled person was found to associate with participation in screening and with
      intentions about selective termination, women's perceptions of lives of the
      disabled should receive more attention in future studies.

PMID- 10085504
TI  - Equalization of amniotic fluid volumes after decompression amniocentesis for
      treatment of the twin oligohydramnios-polyhydramnios sequence.
AB  - OBJECTIVE: To measure acute and chronic changes in the placenta and amniotic
      fluid associated with performance of decompression amniocentesis in pregnancies
      with the twin oligohydramnios-polyhydramnios sequence (TOPS). METHODS: Amniotic
      fluid pressures, placental thickness, placental perfusion, and amniotic fluid
      volumes were measured in each sac of a monochorionic diamniotic twin gestation
      before and after decompression amniocentesis. Indigo carmine was injected into
      the polyhydramnic sac after decompression, and fluid from the oligohydramnic sac
      was sampled after equilibration. Spectrophotometric analysis of amniotic fluid
      specimens was performed for dye detection. Amniotic fluid volume and placental
      perfusion studies were repeated 1 week later. RESULTS: Three patients with TOPS
      were enrolled, and decompression amniocentesis was performed in the midtrimester.
      After decompression, amniotic fluid volume decreased in the polyhydramnic sac,
      amniotic fluid pressures decreased in both sacs, placental thickness increased,
      and umbilical artery Doppler velocimetry was unaffected. The amniotic fluid
      volume increased acutely in only one oligohydramnic sac after decompression, and
      ultrasonographic examination, amniotic fluid spectrophotometric analysis, and
      placental pathologic examination all identified interfetal membrane disruption as
      the etiology. CONCLUSIONS: Decompression amniocentesis as a treatment for TOPS
      does not result in acute or chronic changes in the amniotic fluid volume of the
      oligohydramnic sac in the absence of interfetal membrane disruption.

PMID- 10085505
TI  - Doppler study on pulmonary venous flow in the human fetus.
AB  - OBJECTIVES: The fetal pulmonary circulation is different from the postnatal
      circulation: the flow is small. The arterial pressure is almost systemic, and the
      vascular resistance is high. Moreover, lungs are collapsed in the fetus. However,
      the pulmonary venous flow in the fetus has not been studied. The aims of this
      study were to look at flow patterns of pulmonary venous system in the fetus and
      to see whether there are any changes in Doppler parameters with fetal growth.
      METHODS: The pulmonary venous flow velocity was analyzed in 56 normal human
      fetuses. The fetal gestational age ranged from 17 to 37 weeks. Pulsed-Doppler
      echocardiography was used to investigate the right upper pulmonary vein in four
      chamber view. After the pulmonary venous signal was obtained, by enlarging the
      sample size, the pulmonary arterial signal was superimposed for timing. Heart
      rate velocities at systolic peak (S), at diastolic peak (D), at nadir between S
      and D (O), and at nadir between D and the next S (X) and velocity-time integral
      were measured. RESULTS: The pulmonary venous signal showed basically continuous
      flow from pulmonary vein toward left atrium through all the cardiac cycles, and
      it had biphasic peaks: one during the systolic and the other during the diastolic
      phase. The systolic peak of pulmonary vein occurred slightly earlier or later
      than the systolic upstroke of pulmonary arterial waveforms. The systolic peak of
      pulmonary vein was higher than the diastolic peak in 45 out of 56 cases.
      Velocities of systolic and diastolic peaks and velocity-time integral of the
      pulmonary vein have significantly increased with fetal growth. CONCLUSIONS: In
      the fetus, the flow pattern of the pulmonary vein was similar to that of the
      postnatal pattern with the exception of absence of atrial reversal. Lower
      velocities may reflect a decreased pulmonary flow volume.

PMID- 10085506
TI  - Alteration in the low-frequency domain in power spectral analysis of fetal heart
      beat fluctuations.
AB  - OBJECTIVE: Spectral analysis was conducted on fetal heart rate fluctuations for
      the purpose of investigating the change in gestational age and examining the
      usefulness as a method of estimating fetal blood gas. STUDY DESIGN: Five hundred
      and twenty-nine pregnant women with a single normal fetus and 26 women with
      intrauterine growth restriction (IUGR) were studied during the 20th to 38th
      gestational weeks. In cases of IUGR, fetal blood gas levels were evaluated with
      percutaneous umbilical blood sampling. A time series of fetal heart rate
      fluctuation was obtained with a 1. 15-MHz ultrasonic transducer, and power
      spectral analysis of 200 consecutive stable beats was performed with an
      autoregression method. Integrated areas of 0.025-0.125 cycles/beat were defined
      as low-frequency areas (LFAs) and were examined in normal fetuses. In addition,
      the relation between LFA and fetal blood gas values was studied. RESULTS: As
      pregnancy progressed, LFA increased with a cubic regression equation (Y = 6.484 -
      0.764X + 0.029X2 - 0.00034X3). The correlation coefficient was 0.625 (p < 0.05).
      In the cases of IUGR, DeltaLFA was highly correlated with DeltapO2 and DeltapH
      (correlation coefficient, 0.650 and 0.618, respectively). CONCLUSIONS:
      Measurement of LFA provides insight into the development of fetal autonomic
      function and also may serve as a quantitative index of fetal well-being in mid
      pregnancy.

PMID- 10085507
TI  - Iatrogenic monoamniotic twin gestation with progressive twin-twin transfusion
      syndrome.
AB  - OBJECTIVE: Intentional puncture of the membrane has been reported to be a
      promising new method for the management of twin-twin transfusion syndrome. CASE
      REPORT: Treatment of twin-twin transfusion syndrome with serial amniocenteses
      resulted in unintentional puncture of the dividing membrane at 24 weeks of
      gestation. Fetal growth discordance increased, and twin-twin transfusion did not
      improve following the puncture. Intrauterine death of both fetuses at 27 weeks of
      gestation occurred. CONCLUSION: Amniotic septostomy for the treatment of twin
      twin transfusion syndrome should be performed with serious consideration.

PMID- 10085508
TI  - Hodgkin's disease during pregnancy: diagnostic and therapeutic management.
AB  - OBJECTIVES: To evaluate the possibility that women affected by Hodgkin's disease
      (HD) during their second or third trimester of pregnancy can safely carry their
      pregnancy to term. METHODS: From 1986 to 1997, 6 women came to our Center during
      the second trimester of pregnancy and were diagnosed as having HD. Three of these
      6 patients were treated with chemotherapy before delivery and 3 of them were kept
      under observation and started treatment after delivery. RESULTS: All 6 women gave
      birth to a healthy female. CONCLUSIONS: The pregnancy does not worsen the course
      of the illness and does not compromise long-term clinical remission and recovery.

PMID- 10085509
TI  - High levels of maternal serum human chorionic gonadotropin in Down syndrome
      pregnancies: the possible role of a transcription factor on chromosome 21.
AB  - Increased levels of human chorionic gonadotropin (hCG) are used as markers for
      Down syndrome (DS) screening of low-risk populations. The pathophysiology for
      increased hCG levels remains unknown. In general, hCG synthesis is limited by the
      rate of beta-chain formation. In the placenta, 2 of a total of 6 hCG beta-genes
      are expressed. We hypothesized that in DS, a transcriptional factor may
      upregulate beta-chain transcription by interacting with the beta5-promoter.
      Primary cell cultures of skin fibroblasts from both normal and DS midtrimester
      fetuses were established and transfected with the beta5-promoter linked to the
      chloramphenicol-acetyl-transferase reporter gene. The chloramphenicol-acetyl
      transferase activity was measured. Three of six DS-derived cell cultures showed a
      three-fold increase in acetylation. The increase in hCG promoter activity in DS
      derived fibroblasts suggests a possible role for a transcriptional factor located
      on the human chromosome 21 by either directly or indirectly interacting with the
      beta5-promoter.

PMID- 10085510
TI  - Efficiency of ultrasound and biochemical markers for Down's syndrome risk
      screening. A prospective study.
AB  - OBJECTIVE: To evaluate the sequential combination of ultrasound screening for
      fetal aneuploidy at 11-14 weeks with maternal biochemistry at 12-14 and 15-18
      weeks of gestation. METHODS: A prospective study including 1,656 women, with a
      singleton pregnancy booked before 13 weeks of gestation. Nuchal translucency (NT)
      thickness was measured by transabdominal ultrasound examination. alpha
      Fetoprotein, free betahCG and hCG were measured by immunoradiometric (12-14
      weeks) or immunometric (15-18 weeks) assays. Derived risks were then calculated.
      Cutoff risks were chosen first arbitrarily at 1/250 and then adjusted for a 5%
      false-positive rate. RESULTS: Seven fetal aneuploidies were diagnosed, including
      5 Down's syndromes, 1 trisomy 18 and 1 triploidy. Three Down's syndromes had
      concordant high risk with the 3 screenings. One was at low risk with NT, and
      another was at low risk by maternal serum screening, but sequential combination
      of screenings led to a 100% detection rate with cutoffs of 1/240, 1/160 and 1/250
      for NT, first- and second-trimester biochemistry, respectively (i.e. for a cutoff
      adjusted for a 5% false-positive rate). CONCLUSION: This preliminary study
      suggests a benefit in combining maternal age-related risk together with NT and
      biochemical markers in the first or the second trimester. The algorithm combining
      these risks needs to be established in a wide population.

PMID- 10085511
TI  - Fetoscopy in the pregnant rabbit at midgestation.
AB  - OBJECTIVE: To develop a small animal model for fetoscopy. METHODS: In 12 time
      dated pregnant rabbits at 22 days' gestational age (term 32 days) one amniotic
      sac in each uterine horn (n = 24) was used for a fetoscopic procedure. After
      laparotomy, a 2- to 3-mm microsurgical myometrial incision was made to expose the
      chorionic and amniotic membrane. Under microscopic control, a 2-mm needle was
      inserted into the amniotic sac. Through this a 1.2-mm endoscope was passed to
      carry out fetoscopy during maximally 10 min, using 5-10 ml saline amnioinfusion.
      Mean outcome measurements were ability to visualize the placenta, umbilical cord
      and the different fetal elements during fetoscopy, as well as fetal survival and
      weight at second-look operation at 30 days. The untreated amniotic sacs served as
      negative controls. RESULTS: In all cases, fetoscopy could be carried out
      successfully, and all fetuses survived till delivery without significant
      influence on fetal birth weight. CONCLUSION: The midgestational rabbit can be
      used to perform fetoscopy.

PMID- 10085512
TI  - Antenatal diagnosis of Bart's hydrops fetalis [correction of homozygous alpha
      thalassemia]. A case report.
AB  - OBJECTIVE: Diagnosis of the Bart's hydrops fetalis [corrected]. METHOD: Bart's
      hydrops fetalis [corrected] was discovered by chance in the fetus of a female
      Chinese patient. Major intrauterine growth retardation, oligohydramnios, an
      immobile fetus, and cardiomegaly were the principal echographic signs.
      Cordocentesis showed fetal anemia, and electrophoresis of fetal hemoglobin
      revealed the presence of Bart's hemoglobin. RESULT: As there is no known
      effective treatment, termination of pregnancy was proposed to the patient.
      CONCLUSIONS: Bart's hydrops fetallis [corrected] is a lethal condition. Early
      echographic signs (cardiothoracic index >0.50, placental thickening) can be
      screened during weeks 17-18 or even during weeks 13-14 of gestation. These signs
      would permit a reduction of invasive examinations in couples at risk.

PMID- 10085513
TI  - The psychosocial impact on high-risk pregnant women of a noninvasive prenatal
      diagnostic test.

PMID- 10085514
TI  - Anthropoid origins and the modern symphysis.
AB  - To highlight adaptive transformations in craniomandibular form during anthropoid
      origins, symphyseal character states and underlying masticatory loading regimes
      were investigated vis-a-vis shifts in diet and body size. A study of fossil
      anthropoids is possible because variation in symphyseal fusion is continuous and
      directly proportional to the amount of symphyseal stress and because such
      variation can be considered a series of discrete character states each with
      unique functional underpinnings. Using recent systematic renderings of Eocene and
      Oligocene taxa as a template with which to assess character evolution, this
      analysis indicates when, and in which clade(s), specific masticatory features
      became fixed and thus diagnostic. A general trend throughout early anthropoid
      evolution is for descendent taxa to be progressively larger than ancestral forms.
      Coupled with this pattern is the tendency for larger-bodied fossil anthropoids to
      have ingested tougher diets variably consisting of thick-coated, unripe fruits
      and/or leaves. Mastication of mechanically tougher foods entails greater
      repetitive loading of the mandible and requires relatively larger amounts of
      balancing-side muscle force, thus resulting in correspondingly greater symphyseal
      fusion due to elevated dorsoventral shear. With a single exception, these
      adaptive transformations characterize the evolutionary pathway leading both to
      parapithecines and a catarrhine:platyrrhine clade (crown anthropoids). While the
      ancestor of crown anthropoids would have possessed a body size, diet and
      masticatory adaptations similar to parapithecines, such a common suite of
      features evolved independently. Moreover, the evolution of an early-fusing
      symphysis and associated wishboning loading regime of catarrhines and
      platyrrhines is unique among all anthropoids. Lastly, the apparent lack of
      reversals in symphyseal fusion indicates the improbability of phylogenetic
      hypotheses in which a relationship is proposed between 'ancestral' taxa with a
      greater degree of symphyseal fusion and 'descendent' anthropoids with a lesser
      degree of ossification.

PMID- 10085515
TI  - Social structure and seasonal variation in the behaviour of Eulemur mongoz.
AB  - Data presented here were collected during a 10-month study carried out on the
      mongoose lemur, Eulemur mongoz, at Anjamena in northwestern Madagascar. Baseline
      information is provided on behaviour and assessed for seasonal variation. Given
      the highly seasonal nature of the environment, remarkably little behavioural
      variation was observed. This may be directly linked to the cathemeral activity
      pattern, where differential movement into either the diurnal or the nocturnal
      'niche' could reduce the effect of selective seasonal pressures, thus reducing
      behavioural and ecological adaptation to seasonal variation. The behavioural
      mechanisms of reinforcement of the pair bond through close proximity, mutual
      anogenital marking, paternal participation in the care of offspring and
      territoriality are all in accord with the general characteristics of monogamy in
      primates. The feature of mate monopolization by males, proposed as typical of
      monogamous social systems, seems to be more attributable to females in E. mongoz,
      as only they exhibit high levels of intrasexual aggression. Female dominance,
      characteristic of most species of lemur, may thus include more than just female
      feeding priority in E. mongoz.

PMID- 10085516
TI  - Development of the female great call in Hylobates gabriellae: A case study.
AB  - Although the structure of adult gibbon duet singing has been characterised in
      most species, little is known about the ontogeny of gibbon song. The present
      study describes the developmental trajectory of the female great call in a
      captive infant Hylobates gabriellae female, on the basis of periodic tape
      recordings made while she participated in the duetting of her parents. The major
      part of great call development is completed between 5 and 32 months of age, and a
      differential time course is apparent for different portions of the female great
      call, raising the question of the role of the protracted period of vocal
      development in this species.

PMID- 10085518
TI  - Expansion of the known distribution of Goeldi's monkey (Callimico goeldii) in
      south-western brazilian amazonia 

PMID- 10085517
TI  - Survey of Goeldi's monkeys (Callimico goeldii) in northern bolivia 

PMID- 10085519
TI  - A preliminary report on sichuan snub-nosed monkeys (Rhinopithecus roxellana) at
      baihe nature reserve 

PMID- 10085520
TI  - Scent marking and contact call production in ring-tailed Lemurs (Lemur catta).

PMID- 10085521
TI  - Liquid-stored red blood cells for transfusion. A status report.
AB  - Blood transfusion in a modern sense means the transfusion of red cells, when
      necessary supplemented by other components. The demand for plasma and plasma
      fractions and for platelets for therapeutic use has had an influence on the
      technique for preparing red cells. Automated devices have made it possible to
      perform collection as well as separation under more standardized conditions.
      Improved techniques for storage of red cells have prolonged the shelf life
      somewhat but most of the available methods disregard the rapid loss of 2,3
      diphosphoglycerate and the accompanying increase in oxygen affinity. Methods are
      available which reduce the number of contaminating leukocytes to low levels, but
      information is still incomplete as to the degree of depletion actually needed.

PMID- 10085522
TI  - Hepatitis E virus: relevance in blood donors and risk groups.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) infection usually causes acute
      self-limited disease. HEV is associated with faecal-contaminated drinking water,
      but other vectors, such as blood, are possible. The aim of this study was to
      investigate the prevalence of HEV in blood donors and in two groups at high risk
      for parenteral infections, namely, haemodialysis patients, and children infected
      with HCV via blood transfusion. MATERIALS AND METHODS: We investigated the
      prevalence of anti-HEV in 863 blood donors, 63 haemodialysis patients, and 42
      children infected post transfusion with HCV. RESULTS: The prevalence rates were
      2.8, 6.3%, and zero, respectively. CONCLUSIONS: (1) The incidence of HEV in Spain
      is similar to that in other Western European countries, and (2) HEV is probably
      not transmitted parenterally to children.

PMID- 10085523
TI  - GB virus type C viremia and envelope antibodies among population subsets in The
      Netherlands.
AB  - BACKGROUND AND OBJECTIVES: Two new flaviviruses, hepatitis G virus and GB virus
      type C (GBV-C), are possible causative agents for non-A-E hepatitis. In this
      study we established the prevalence of GBV-C markers in various population
      subsets in The Netherlands by assays for GBV-C antibodies and GBV-C nucleic acid.
      MATERIALS AND METHODS: We tested specimens from groups of patients with hepatitis
      of various causes, intravenous drug users (IVDUs), and blood donors for GBV-C RNA
      (LCx(R) GBV-C assay, Abbott Laboratories), and for antibodies to the GBV-C
      envelope E2 protein (GBV-C anti-E2) with an enzyme immunoassay (Abbott
      Laboratories). Patients and donors were represented in one group only. RESULTS:
      GBV-C RNA and GBV-C anti-E2 prevalence were, respectively, 2/34 (6%) and 3/34
      (9%) among patients with non-A-E hepatitis, 2/10 (20%) and 0/10 (0%) among
      hepatitis B virus patients, 10/40 (25%) and 19/40 (48%) among hepatitis C virus
      (HCV) patients, 1/8 (13%) and 0/8 (0%) among patients with autoimmune hepatitis
      (AIH), 24/102 (24%) and 72/102 (71%) among IVDUs, 1/34 (3%) and 2/34 (6%) among
      blood donors with indeterminate anti-HCV recombinant immunoblot assay reactivity,
      and 3/250 (1.2%) and 8/250 (3.2%) among first-time blood donors. The profile of
      simultaneous GBV-C RNA positivity plus GBV-C anti-E2 positivity was found in 2/40
      (5%) HCV patients, 4/102 (4%) IVDUs, and 1/250 (0.4%) first time blood donors.
      CONCLUSION: GBV-C infection appears not to be a major cause of non-A-E hepatitis
      and AIH, but is associated with parenteral risk. The prevalence of GBV-C viremia
      in first time blood donors is higher than that of HCV (1.2 vs. 0.04%), but GBV-C
      viremia in IVDUs is lower than HCV (24 vs. 59%). Most IVDUs have probably
      previously been exposed to GBV-C given the very high prevalence of GBV-C anti-E2
      (71%). Most persons with GBV-C markers are GBV-C RNA-negative and anti-E2
      confirmed positive, suggesting that GBV-C infection is transient.

PMID- 10085524
TI  - A very-high-purity von Willebrand factor preparation containing high-molecular
      weight multimers.
AB  - BACKGROUND AND OBJECTIVES: We investigated large-scale production of very-high
      purity von Willebrand factor (vWf) containing high-molecular-weight vWf
      multimers, using chromatography alone. MATERIALS AND METHODS: Factor VIII (FVIII)
      containing vWf was produced by initial separation of vWf from plasma by gel
      filtration followed by two ion exchange steps. Two virus inactivation steps were
      incorporated in the process. RESULTS: The process resulted in FVIII-containing
      vWf preparations with a mean specific activity of 82 U vWf: collagen-binding
      activity per milligram protein (excluding added albumin) and with almost intact
      vWf multimer distributions. CONCLUSIONS: Very-high-purity, double virus
      inactivated vWf preparations containing high molecular weight multimers were
      obtained on a production scale.

PMID- 10085525
TI  - Automated separation of whole blood in top and bottom bags into components using
      the Compomat G4.
AB  - BACKGROUND AND OBJECTIVES: Whole blood can be separated by hard spin
      centrifugation into layers of blood components according to their specific
      gravity. The aim was to develop a program for an automatic separator to
      subsequently express the various components into their respective satellite bags
      in top and bottom systems with the following requirements: a red cell concentrate
      with a low leukocyte and platelet contamination, a 'cell-free' plasma, and a
      buffy coat with a volume of about 50 ml with an acceptable loss of red cells.
      MATERIALS AND METHODS: The Compomat G4 possesses an independently moving upper
      and lower press, to automatically express plasma or red cells to satellite bags
      of top and bottom systems. The influence of the extension of the lower press was
      studied by pooling and dividing two units of whole blood, and separating these
      units after centrifugation (2,960 g, 10 min) either with a program where the
      lower press was completely extended (program C), or with a program that left
      approximately 1 mm between the door and the lower press (program D). RESULTS: The
      program (program D), where the lower press was not completely extended, yielded a
      buffy coat with a volume of 52+/-1 ml (mean +/- SD, n = 36), which contained >75%
      leukocytes and >90% platelets of the original whole blood unit, with a red cell
      loss in the buffy coat of 21+/-1 ml (10.8+/-0.8% of the original volume). The
      leukocyte content of the red cell concentrates was 775+/-379x10(6) per unit,
      whereas the plasma contained 3+/-3x10(6) leukocytes and 4+/-3x10(9) platelets per
      unit. The pooling experiment indicated that complete extension of the lower press
      (program C) resulted in a significantly higher leukocyte contamination of the red
      cell concentrate (788+/-431x10(6 ) vs. 658+/-419x10(6); n = 12; p = 0.03), while
      there was no difference in the yield of red cells or plasma. The buffy coat
      produced with program D contained significantly more leukocytes (2,242 +/
      396x10(6) vs. 2,065+/-327x10(6), p = 0.005) and more platelets (96+/-14x10(9) vs.
      92+/-17x10(9), p = 0.02) per unit than with program C, probably because buffy
      coat cells sticking to the container wall are not expressed to the red cell
      concentrate, and thus remain in the buffy coat bag. Therefore, program D met our
      specifications for blood products. CONCLUSIONS: The Compomat G4 warrants
      reproducible separation of whole blood in top and bottom bags into red cells,
      buffy coat and plasma meeting our specifications.

PMID- 10085526
TI  - Cytokine generation in whole blood, leukocyte-depleted and temporarily warmed red
      blood cell concentrates.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that inflammatory cytokines such
      as Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8
      might be responsible for a large number of non-antibody-mediated adverse
      reactions to the transfusion of blood components, especially of platelet
      concentrates (PCs). The aim of this study was to compare the levels of
      proinflammatory cytokines in different blood components containing red cells such
      as buffy-coat-free packed red cells (RBCs), filtered RBCs and whole blood (WB)
      during storage under several conditions. MATERIALS AND METHODS: WB (CPD-A1, n =
      16) was stored for 35 days at 2-6 degrees C; samples were taken on days 0, 21 and
      35. Buffy-coat-poor RBCs in additive solution PAGGS-M (n = 16) were divided into
      halves, one half was leukocyte (WBC)-depleted by filtration on day 0, both halves
      were stored for 49 days at 2-6 degrees C (samples: days 0, 21, 49). Furthermore,
      buffy-coat-poor, unfiltered SAG-M RBCs (n = 16) were halved immediately after
      production and stored at 2-6 degrees C until day 42 (samples: days 0, 21, 42).
      One half remained at room temperature for 24 h on day 3. Cytokine levels were
      determined with commercial enzyme-linked immunosorbent assays. RESULTS: Levels of
      IL-1beta and TNF-alpha rose during storage of WB and RBCs. IL-6 could be detected
      markedly above the detection threshold in WB only. At the end of storage, we
      detected IL-8 in 1 of 16 units of WB tested, in 10 of 16 standard PAGGS-M RBCs
      and in 15 of 16 temporarily warmed SAG-M RBCs. Prestorage filtration of RBCs
      prevented the accumulation of IL-1beta and TNF-alpha. Temporarily warming of RBCs
      for 24 h did not cause any substantial increase in cytokine levels other than IL
      8. RBCs stored in different additive solutions (PAGGS-M versus SAG-M) showed
      similar cytokine concentrations during storage. The cytokine content of WB was
      very similar to that of buffy-coat-poor RBCs. CONCLUSION: Cytokine levels
      measured in WB and buffy-coat-poor RBCs result in levels which are unlikely to
      cause febrile reactions even in the case of massive transfusion. We conclude
      that, according to present knowledge, there is no reason for prestorage
      filtration of buffy-coat-poor RBCs or WB to avoid febrile transfusion reactions
      due to cytokine accumulation during storage.

PMID- 10085527
TI  - Search for the sialic acid-independent receptor on red blood cells for invasion
      by Plasmodium falciparum.
AB  - BACKGROUND AND OBJECTIVES: Plasmodium falciparum uses multiple red blood cell
      (RBC) receptors and parasite ligands to invade RBCs. One pathway uses a sialic
      acid-independent protein or carbohydrate for invasion. The present study searches
      for this RBC receptor. MATERIALS AND METHODS: We determined whether antigen
      negative and null RBCs (including PNH cells that lack all glycosylphosphatidyl
      inositol-linked proteins) could be invaded after neuraminidase treatment. We used
      two P. falciparum clones for the study: one that requires sialic acid for
      invasion and was an indication of removal of sialic acid and a second clone that
      can invade neuraminidase-treated RBCs. RESULTS: All neuraminidase-treated variant
      RBCs in this study were invaded. CONCLUSION: This study indicates that some
      molecule other than those studied (e.g., a carbohydrate) is the receptor for the
      sialic acid-independent pathway. This powerful tool for the identification of
      receptors for microorganisms should be used more extensively.

PMID- 10085528
TI  - A newly identified nonsecretor allele of the human histo-blood group
      alpha(1,2)fucosyltransferase gene (FUT2).
AB  - BACKGROUND AND OBJECTIVES: The human Secretor alpha(1, 2)fucosyltransferase gene
      determines the ABH secretor status and influences the Lewis phenotype of an
      individual. Studies were carried out on the Lewis (a+b-) nonsecretors of
      different groups indigenous to Taiwan to demonstrate their se genotypes. METHODS:
      The Lewis phenotype of the blood samples was determined by a microplate method.
      The se genotypes of the individuals with the Lewis (a+b-) phenotype were analyzed
      by a polymerase chain reaction restriction fragment length polymorphism (PCR
      RFLP) method designed for the se alleles reported previously. PCR and cloning
      techniques were used to determine the coding sequence of the novel se gene.
      RESULTS: A new se allele, se685, with a three-nucleotide deletion of GTGGT to GT
      in the coding region of nucleotides 685 through 689 was identified in a Le (a+b-)
      nonsecretor from the Ami tribe indigenous to Taiwan. The deletion predicts the
      loss of the amino acid Val230 in the corresponding secretor enzyme's C-terminal
      segment. The distribution of the se685 allele in the Ami tribe was further
      verified by PCR-RFLP analysis. CONCLUSION: The Se gene exhibits heterogeneity
      with some Se alleles being common but others displaying a unique distribution in
      different ethnic populations. The newly identified se685 allele seems to exist
      only in the Ami tribe indigenous to Taiwan.

PMID- 10085529
TI  - Pan-reactive platelet antibodies in post-transfusion purpura.
AB  - BACKGROUND AND OBJECTIVES: The mechanism for the destruction of a patient's own
      platelets in post-transfusion purpura (PTP) is unknown. In order to test the
      hypothesis that the destruction of autologous platelets in PTP is related to the
      presence of platelet antibodies with pan-reactivity, we investigated sera from
      patients with PTP. MATERIALS AND METHODS: Sera from 12 patients with PTP were
      investigated for platelet antibodies by platelet-ELISA and monoclonal antibody
      specific immobilization of platelet antigen assay. RESULTS: During the
      thrombocytopenic phase, antibodies of IgG and IgM classes with pan-specificity
      against platelet GPIIb-IIIa, GPIb-IX and GPIa-IIa were found together with HPA
      alloantibodies. After recovery, the pan-specific antibodies disappeared or the
      extent of reactivity diminished, whereas the IgG HPA alloantibodies persisted.
      CONCLUSION: These findings provide evidence that transient panreactive antibodies
      may be responsible for the autologous platelet destruction in PTP.

PMID- 10085530
TI  - Hepatitis C virus stability: the issue!

PMID- 10085531
TI  - Ocular torticollis and facial asymmetry.
AB  - OBJECTIVE: Ocular torticollis secondary to congenital superior oblique palsy can
      be associated with facial asymmetry. The purpose of this study was to determine
      if other ocular causes of head tilting also carry the same association. DESIGN:
      The study design was clinical evaluation of patients. PARTICIPANTS: Fifteen
      patients with marked, moderate, or mild head tilts associated with dissociated
      vertical deviation (DVD), and 3 patients with nystagmus and a torsional null
      point. A control group was comprised of 3 patients with congenital superior
      oblique palsy, 3 with traumatic superior oblique palsy, and two normal patients.
      INTERVENTION: A masked observer analyzed full-face photographs of the subjects.
      MAIN OUTCOME MEASURE: The presence of facial asymmetry. RESULTS: Facial asymmetry
      due to bending in/of the sagittal plane of at least two degrees was found in 3 of
      4 patients with a marked head tilt from DVD, in 2 of 5 five patients with a
      moderate head tilt from DVD, in one of 3 patients with a head tilt due to
      nystagmus, and in one of 3 patients with a head tilt due to congenital superior
      oblique palsy. None of the patients with a mild head tilt from DVD, traumatic
      superior oblique palsy, or the normal controls had clinically noticeable facial
      asymmetry. CONCLUSION: Facial asymmetry can be associated with abnormal head
      postures, specifically, large head tilts from DVD or nystagmus.

PMID- 10085532
TI  - The immediate effect of bilateral superior obliuqe tenotomy on primary position
      horizontal binocular alignment.
AB  - PURPOSE: To evaluate the effect on primary position horizontal binocular
      alignment of superior oblique tenotomy for A-pattern exotropia with bilateral
      superior oblique overaction using new surgical and anesthesia techniques.
      SUBJECTS AND METHODS: We performed intraoperatively adjustable horizontal
      strabismus surgery under topical anesthesia in 6 cases of A-pattern exotropia.
      After adjusting the horizontal deviation nearly to orthotropia in primary
      position, we measured the angle of horizontal deviation in up-, primary, and
      downgaze positions. This was followed by bilateral superior oblique tenotomy and
      remeasurement of the horizontal deviation in the same 3 positions.
      Postoperatively we remeasured the deviation at one day, one month and three
      months. RESULTS: There was no immediate change in the horizontal deviation in
      primary position in 2 of the 6 patients, and 3-8 delta of immediate esotropic
      shift in 4 of the 6 patients (average 3.3 delta) after bilateral superior oblique
      tenotomy. At 3 months postop' the small esotropia noted at the immediate postop'
      measurement became orthotropic. There was a tendency of increased exotropic shift
      or becoming exotropic in those patients with slight exotropia or orthotropia at
      the immediate postop' measurement. But these shifts were minimal. CONCLUSION:
      When combined surgery of superior oblique and horizontal muscle is planned for A
      pattern exotropia, the effect of bilateral superior oblique tenotomy on the
      primary position horizontal binocular alignment can be disregarded.

PMID- 10085533
TI  - A case of divergent strabismus fixus.

PMID- 10085534
TI  - A survival analysis of communal-living, self-help, addiction recovery
      participants.
AB  - We examined individual and group characteristics associated with the duration of
      community involvement (i.e., length of residence) in 11 Illinois Oxford Houses
      for 129 male recovering addicts. Survival analyses indicated that the best
      predictor of duration of community involvement from demographic items was age
      (i.e., older age and older age of fellow residents were associated with being
      more likely to continue residence). Among psychological measures, the best
      survival predictor was lack of pessimism of the future. Although the relationship
      between longer length of residence and treatment outcomes are complex, because it
      is often difficult to keep people involved in treatment programs, knowledge that
      we can gain about those factors that might lead to greater lengths of stay are of
      importance.

PMID- 10085535
TI  - The Program Environment Scale: assessing client perceptions of community-based
      programs for the severely mentally ill.
AB  - The Program Environment Scale (PES) was developed for use with clients of
      community-based programs for the severely mentally ill. It is intended to fill
      the gap in available tools for assessing clients' perceptions of program
      functioning as it affects their "quality of life" in a program. Formal pretests
      were conducted with 121 clients at 12 randomly selected programs near Washington,
      DC. The final field test used a revised form (29 domains; 129 items) with 221
      clients in 22 programs selected randomly throughout the U.S., including
      Clubhouse, day treatment, psychosocial rehabilitation, and social club programs.
      Twenty-three subscales met at least five of eight psychometric criteria for
      internal consistency and discriminant validity. A 24th subscale was retained
      because of its substantive importance. Successful subscales cover program
      atmosphere and interactions (program cares about me, energy level, friendliness,
      openness, staff-client and client-client respect, reasonable rules, availability
      of positive physical contact, protection from bad touch, staff investment in
      their jobs, and confidentiality), client empowerment/staff-client equality
      (program and treatment empowerment, egalitarian space use), and service
      components (support for paid work, work importance, emergency access, family
      activities, housing, public benefits, community activities, medications,
      substance abuse, and continuity). Subscale validity is indicated by associations
      of specific service offerings with scores on scales measuring client perceptions
      of those services, and by an ability to differentiate among program models (i.e.,
      Clubhouses, day treatment programs, and psychosocial rehabilitation programs look
      different from each other). Subscale scores were not influenced by client
      characteristics (gender, race, age, diagnosis, number of hospitalizations, length
      of time in program). The final scale has 97 items and takes about 25 minutes to
      complete. The PES succeeds in measuring different aspects of programs as clients
      perceive them. In the programs we visited, directors felt the PES covers the
      important things they want to know about how clients perceive their program. The
      PES should become a useful tool both for researchers interested in how client
      responses to programs may influence their therapeutic outcomes, and for
      practitioners interested in improving their clients' program experiences and/or
      increasing convergence of staff and client views of their program.

PMID- 10085536
TI  - "Nothing about me, without me": participatory action research with self
      help/mutual aid organizations for psychiatric consumer/survivors.
AB  - Participatory action research with self-help/mutual aid organizations for
      psychiatric consumer/survivors is reviewed. We begin by tracing the origins of
      and defining both participatory action research and self-help/mutual aid. In so
      doing, the degree of correspondence between the assumptions/values of
      participatory action research and those of self-help/mutual aid for psychiatric
      consumer/survivors is examined. We argue that participatory action research and
      self-help/mutual aid share four values in common: (a) empowerment, (b) supportive
      relationships, (c) social change, and (d) learning as an ongoing process. Next,
      selected examples of participatory action research with psychiatric
      consumer/survivor-controlled self-help/mutual aid organizations which illustrate
      these shared values are provided. We conclude with recommendations of how the key
      values can be promoted in both the methodological and substantive aspects of
      future participatory action research with self-help/mutual aid organizations for
      psychiatric consumer/survivors.

PMID- 10085537
TI  - The complete sequence and expression patterns of the atrial myosin heavy chain in
      the developing chick.
AB  - We have earlier reported partial cloning of a cDNA of a chick atrial myosin heavy
      chain (MHC) gene, CCSV2 and its expression pattern in embryonic chick hearts
      (Oana et al (1995) Eur J Cell Biol 67, 42-49). In this study, five overlapping
      cDNA clones (including CCSV2) which together encode the entire open reading frame
      of the chick atrial MHC gene were characterized, and both the entire nucleotide
      sequence consisting of 5825 bases and the deduced amino acid sequence consisting
      of 1931 amino acids determined. Reinvestigation of the nucleotide sequence of the
      previously reported and presumably different chick atrial specific MHC cDNA
      clone, AMHC1 (Yutzey et al (1994) Development 120, 871-883), revealed that our
      clone and AMHC1 encoded the same MHC. The chick atrial MHC gene was strongly
      expressed in developing chick atria from a very early stage (Hamburger and
      Hamilton stage 9, 29-33 h) to the adult stage. This gene was also expressed,
      although weakly, in the ventricle, somite (the precursor to skeletal muscle) and
      skeletal muscle during embryonic stages but not in adults.

PMID- 10085538
TI  - Rescue of K562 cells from MDM2-modulated p53-dependent apoptosis by growth factor
      induced differentiation.
AB  - The wild-type human MDM2 protooncogene was tested for its ability to modulate
      apoptotic activity of the de novo expressed p53 tumor suppressor gene in K562
      cells. We also studied the role of some cytokines in this phenomenon. K562, a
      human myeloid leukemia cell line, does not express p53 at the mRNA or protein
      level. In this study, we stably transfected K562 with eukaryotic vectors
      containing either normal p53 cDNA (pC53-SN3) or mutated p53 (143Val-->Ala) cDNA
      (pC53-SCX3). Transfectants expressing WT p53 or those expressing mutant p53 are
      called K562 SN and K562 SM respectively. Many leukemic cell lines undergo
      apoptosis when de novo WT p53 is expressed alone. In contrast, while the
      resulting clones (K562 SN and K562 SM) expressed p53, they did not undergo
      apoptosis. However, when treated with MDM2 mRNA antisense (MDM2 AS)
      oligodeoxynucleotides (ODNs), K562 SN demonstrated apoptotic features at both
      molecular and morphological levels. No change was observed when the other clones
      (K562 and K562 SM) were treated with MDM2 AS. Apoptosis induced in this manner
      was associated with a relatively small increase in intracellular calcium [Ca2+]i.
      Cells cultured in medium previously supplemented with recombinant human (rh)
      interleukin (IL)-3 and rh-erythropoietin (Epo) did not undergo apoptosis.
      Moreover, K562 SN cells were induced to differentiate. This differentiation was
      evaluated by measuring hemoglobin (Hb) level in cellular extracted proteins and
      by analyzing erythroid colony number and morphology. High Hb synthesis was
      obtained when K562 SN cells were cultured with cytokines (IL-3 + Epo) combined
      with MDM2 AS. Our results are consistent with the hypothesis that the function of
      the proto-oncogene MDM2 is to provide a 'feedback' mechanism for the p53
      dependent pathway of apoptosis that could be shunted toward differentiation.

PMID- 10085539
TI  - The direct visualization of structural array from laminin to dystrophin in
      sarcolemmal vesicles prepared from rat skeletal muscles.
AB  - It has been biochemically shown that dystrophin and alpha- and beta-dystroglycan
      form an oligomeric complex which links laminin, a component of the basement
      membrane, to components of the subsarcolemmal cytoskeleton in skeletal muscle
      fibers. In the present study the dystrophin-glycoprotein complex and its
      structural relationships to laminin and subsarcolemmal cytoskeleton were
      ultrastructurally examined in crude surface membranes prepared from rat skeletal
      muscles. Sarcolemmal vesicles within crude surface membranes were identified and
      characterized by fine protrusions on their outer surface and electron-dense
      materials or patches associated with the inner surface. These two components were
      seen to be in register with each other across the sarcolemma. The fine
      protrusions were immunolabeled by anti-alpha-dystroglycan and reassociated with
      exogenous laminin. Immunolabeling in combination with laminin reassociation
      demonstrated that the electron-dense materials contained dystrophin at laminin
      binding domains of the membrane. In addition, they were often associated with
      very fine filaments. These results provide morphological evidence for the
      biochemically proposed model of molecular array of dystrophin complex from the
      basement membrane to the subsarcolemmal cytoskeleton.

PMID- 10085540
TI  - Maturation of the liver-specific peroxisome versus laminin, collagen IV and
      integrin expression.
AB  - The interaction of cells with extracellular matrix components contributes to
      their specific differentiation. We studied hepatic peroxisomes and their changing
      features during embryonic development, and we immunolocalized in the same tissue
      the extracellular matrix components laminin and collagen IV as well as the
      integrin receptor subunits alpha 1, alpha 2, beta 1, and beta 4. Rat and human
      embryonic liver peroxisome expression were studied at the light- and electron
      microscopic level by means of localizing catalase-, D-amino acid oxidase- and
      polyamine oxidase activities and by means of the immunocytochemistry of six
      peroxisomal proteins. The successive import of catalase and the peroxisomal beta
      oxidation enzymes, the late appearance of the other enzymes, and the gradual
      increase of peroxisomal size and number to adult values occurred as asynchronous
      events. Although still immature, peroxisomes were recognized at every stage
      examined and coexisted with laminin and collagen IV in both species. The beta 1
      integrin subunit was immunodetected as early as at 12.5 days in rat. It was
      concluded that these extracellular matrix factors may be important for the
      differentiation of liver parenchyma from the liverbud stage onwards. However, the
      stepwise maturation of the liver-specific peroxisome suggests the involvement of
      many other regulating factors.

PMID- 10085541
TI  - The pineal organ as a folded retina: immunocytochemical localization of opsins.
AB  - The most simple pineal complex (the pineal and parapineal organs of lampreys),
      consists of saccular evaginations of the diencephalic roof, and has a retina-like
      structure containing photoreceptor cells and secondary neurons. In more
      differentiated vertebrates, the successive folding of the pineal wall multiplies
      the cells and reduces the lumen of the organ, but the pattern of the histological
      organization remains similar to that of lampreys; therefore, we consider the
      histological structure of the pineal organ of higher vertebrates as a 'folded
      retina'. The cell membrane of several pineal photoreceptor outer-segments of
      vertebrates immunoreact with anti-retinal opsin antibodies supporting the view of
      retina-like organization of the pineal. Some other pineal outer segments do not
      react with retinal anti-opsin antibodies, a result suggesting the presence of
      special pineal photopigments in different types of pinealocytes that obviously
      developed during evolution. The chicken pinopsin, detected in the last years, may
      represent one of these unknown photopigments. Using antibodies against chicken
      pinopsin, we compared the immunoreactivity of different photoreceptors of the
      pineal organs from cyclostomes to birds at the light and electron microscopic
      levels. We found pinopsin immunoreaction on all pinealocytes of birds and on the
      rhodopsin-negative large reptilian pinealocytes. As the pinopsin has an
      absorption maximum at 470 nm, these avian and reptilian immunoreactive
      pinealocytes can be regarded as green-blue light-sensitive photoreceptors. Only a
      weak immunoreaction was observed on the frog and fish pinealocytes and no
      reaction was seen in cyclostomes and in the frontal organ of reptiles. Some
      photoreceptors of the retina of various species also reacted the pinopsin
      antibodies, therefore, pinopsin must have certain sequential similarity to
      individual retinal opsins of some vertebrates.

PMID- 10085542
TI  - The ability of odours to serve as state-dependent cues for real-world memories:
      can Viking smells aid the recall of Viking experiences?
AB  - This study determined the extent to which re-exposure to the unique combination
      of odours present in a museum (the Jorvik Viking Centre in York) aids the recall
      of a previous visit to the museum, which had typically taken place several years
      earlier. To test this, three groups of participants completed questionnaires
      about the contents of the museum, but in different conditions. One group
      completed the questionnaire in the presence of exactly the same distinctive
      odours as those present in the museum at the time of their original visit. Those
      in two other groups were given either a different (control) set of odours or no
      odours at all. After a brief delay, the same questionnaire was presented again to
      participants in all three groups. Those who had initially been given a novel
      (control) set of odours were now tested in the presence of the genuine Jorvik
      museum odours, while the group that had received the Jorvik odours were now
      tested with the control odours. The third group received no odours on either
      test. Only the novel odour-Jorvik odours condition led to a highly significant
      improvement in performance. This interaction showed that the museum odours could
      act as effective retrieval cues for this incidentally acquired, real-world
      episode.

PMID- 10085543
TI  - Experimental tests of prospective remembering: the influence of cue-event
      frequency on performance.
AB  - During recent years there has been an upsurge of interest in the processes
      underlying success or failure of intentions to perform an action in the future
      e.g. carry out an errand for a friend. Much of this research focuses on
      simulating these delayed-intention or prospective-memory tasks in the laboratory.
      A currently popular variant of these tasks is a repeated-instance event-based one
      in which the same action should be performed whenever a particular (repeated)
      event-cue occurs during an ongoing activity (e.g. a word in a running memory test
      of word recall). We report two experiments that investigated important dimensions
      of this task design, along which recent experimental tasks differ considerably,
      and explored their influence on prospective remembering. The results revealed
      that the variations in the event-cue frequencies explored here did not influence
      overall performance: relatively high event-cue frequency did not improve
      prospective remembering. However, performance was lower when event-cues were
      embedded in a general knowledge test than when a prose-reading task was used.
      Moreover, when remembering was compared for the first and final set of event-cues
      there was evidence for improvement over presentations during the general
      knowledge task and a contrasting decline using the prose task, under high event
      cue frequency conditions only. The results have important repercussions for
      current experimental design and the development of tests of prospective
      remembering skills in particular population subgroups.

PMID- 10085544
TI  - Collective memories, political violence and mental health in Northern Ireland.
AB  - In 1987 one of the most salient incidents in Northern Ireland, involving mass
      casualties, occurred when a bomb exploded in a building near the war memorial in
      the centre of Enniskillen. A total of 63 people were injured and 11 were killed.
      The main aim of the present study was to investigate how salient this event was
      in present day Enniskillen and in a neighbouring town, known here as Lowtown,
      some 8 years after the original incident. The second aim was to examine how
      memories of that particular bomb are related to current psychological well-being.
      Based on interviews with a quota sample of 282 people it was found that
      relatively few people (68) included the Enniskillen bomb when asked to mention
      two Northern Irish events or changes that had taken place over the past 50 years
      that 'come to mind as important to you'. The majority of those who did mention
      the Enniskillen bomb came from Enniskillen and were Protestants. In addition,
      Protestants who mentioned the bomb and those respondents who lived in Lowtown and
      mentioned the bomb scored at a significantly higher level on the General Health
      Questionnaire (indicating poorer mental health).

PMID- 10085545
TI  - An experimental investigation of the role of iconic gestures in lexical access
      using the tip-of-the-tongue phenomenon.
AB  - The tip-of-the-tongue (TOT) state was induced in participants to test Butterworth
      & Hadar's (1989) theory that iconic gestures have a functional role in lexical
      access. Participants were given rare word definitions from which they had to
      retrieve the appropriate lexical item, all of which had been rated high in
      imageability. Half were free to gesture and the other half were instructed to
      fold their arms. Butterworth & Hadar's theory (1989) would predict, first, that
      the TOT state should be associated with iconic gesture and, second, that such
      gestures should assist in this lexical retrieval function. In other words, those
      who were free to gesture should have less trouble in accessing the appropriate
      lexical items. The study found that gestures were associated with lexical search.
      Furthermore, these gestures were sometimes iconic and sufficiently complex and
      elaborate that naive judges could discriminate the lexical item the speaker was
      searching for from a set of five alternatives, at a level far above chance. But
      often the gestures associated with lexical search were not iconic in nature, and
      furthermore there was no evidence that the presence of the iconic gesture itself
      actually helped the speaker find the lexical item they were searching for. This
      experimental result has important implications for models of linguistic
      production, which posit an important processing role for iconic gestures in the
      processes of lexical selection.

PMID- 10085546
TI  - The mental model theory of spatial reasoning re-examined: the role of relevance
      in premise order.
AB  - The effect of premise order on spatial reasoning was investigated using a
      paradigm introduced by Byrne & Johnson-Laird in 1989. Three kinds of problems
      were developed: the first of these was expected to prompt one mental model,
      whereas the second and third were expected to prompt two mental models. The two
      model problems differed from each other by the position (first or last) of a
      premise which was responsible for an indeterminacy. On the basis of Sperber &
      Wilson's Relevance theory, published in 1986 and 1995, it was predicted and
      observed that a two-model problem with the crucial premise in the last position
      was easier than a two-model problem with the crucial premise in the first
      position. Moreover, it was predicted and observed that the two-model problem with
      the crucial premise in the last position was as easy as the one-model problem.
      Implications of these results for the standard mental model theory of spatial
      reasoning are discussed.

PMID- 10085547
TI  - Critical thinking and belief in the paranormal: a re-evaluation.
AB  - This paper evaluates the claim that believers in the paranormal exhibit poor
      critical thinking ability relative to disbelievers, as manifested in their
      inability to evaluate the competence of experimental abstracts. It is argued that
      such differences reported elsewhere (Alcock & Otis, 1980; Gray & Mill, 1990) may
      be accountable for in terms of the action of cognitive dissonance, or as due to
      experimental artifacts. A study was conducted which attempted to overcome earlier
      methodological shortcomings, and which assessed the cognitive dissonance account
      of differential performance. Altogether, 117 participants were characterized as
      believers, neutrals or disbelievers according to a pre-measure. Subsequently,
      each participant was asked to evaluate an abbreviated experimental report which
      was either sympathetic or unsympathetic to parapsychology. No differences in
      assessment ratings were found, failing to replicate the claimed effect and
      supporting an account in terms of artifact. There was a significant tendency for
      those participants who received a paper which was incongruent with their a priori
      beliefs to rate it as less competently conducted and analysed than those who
      rated the congruent paper, in keeping with the cognitive dissonance account.

PMID- 10085548
TI  - Occupational choice and patterns of cognitive abilities.
AB  - Previous studies by Govier and colleagues have shown dichotic listening
      performance to be related to occupation. The results of these studies were
      interpreted as supporting the view that both occupational choice and dichotic
      listening asymmetries depend upon biologically determined aspects of brain
      organization. The present study sought to test further the link between
      occupation and cognition by investigating the patterns of spatial and verbal
      abilities in males and females in male-dominated occupations and males and
      females in female-dominated occupations. It was hypothesized that occupational
      choice would be a salient marker for within-sex variation on cognitive tasks
      previously shown to differentiate performance in men and women. The results
      supported the hypothesis, and are interpreted as strengthening the view that
      occupational choice is, at least in part, a function of an individual's cognitive
      organization.

PMID- 10085549
TI  - Failure to support the right-shift theory's hypothesis of a 'heterozygote
      advantage' for cognitive abilities.
AB  - Annett's (1985) 'right-shift' theory of language dominance and handedness posits
      three genotypes, rs++, rs(+)- and rs(-)-, and Annett has hypothesized that there
      are cognitive ability correlates of these genotypes. The rs++ genotype person is
      held to be 'at risk' for maldevelopment of spatial or other right hemisphere
      based cognitive abilities, and the rs(-)- genotype individual is held to be at
      risk for maldevelopment of phonological abilities. Noting that there must be some
      adaptive advantage conferred by the heterozygous genotype for it to have survived
      over a presumably long period of evolution, Annett has hypothesized that
      heterozygotes are afforded an adaptive advantage over homozygotes because of
      their freedom from 'risks' to intelligence generally. Annett and colleagues have
      used two different indices, or markers, from which they have inferred differing
      concentrations of the three genotypes within groups of participants. One marker,
      based on responses to hand preference items of the Annett Handedness Inventory,
      was found by Annett (1992) to support her theory in that the least dextral of
      right-handed participants did best on spatial tests. The other marker Annett has
      used is based on the degree of right-hand advantage on a simple peg moving speed
      task. The present study utilized both methods and studied the performances of 259
      dextral college men and women on two tests of mental rotation ability and two
      tests of verbal abilities. Results were not supportive of the heterozygote
      advantage hypothesis, and suggested that visuospatial ability was modestly
      related to greater dextrality of participants.

PMID- 10085550
TI  - Using the Internet for psychological research: personality testing on the World
      Wide Web.
AB  - The Internet is increasingly being used as a medium for psychological research.
      To assess the validity of such efforts, an electronic version of Gangestad &
      Snyder's (1985) revised self-monitoring questionnaire was placed at a site on the
      World Wide Web. In all, 963 responses were obtained through the Internet and
      these were compared with those from a group of 224 undergraduates who completed a
      paper-and-pencil version. Comparison of model fit indices obtained through
      confirmatory factor analyses indicated that the Internet-mediated version had
      similar psychometric properties to its conventional equivalent and compared
      favourably as a measure of self-monitoring. Reasons for possible superiority of
      Internet data are discussed. Results support the notion that Web-based
      personality assessment is possible, but stringent validation of test instruments
      is urged.

PMID- 10085551
TI  - Gender differences in the reliability of the EPQ? A bootstrapping approach.
AB  - Reliability indicates the degree of stability or homogeneity of a measurement,
      but also places an upper limit on the degree of association with other variables.
      Various methods are available to estimate the reliability of a measurement scale.
      However, an issue that has rarely been examined is that the reliability of a
      measurement, as estimated by coefficient alpha, may differ between groups. If a
      measurement has a different reliability for groups within a sample, spurious
      moderator effects may occur. The present study examines the reliability of the
      four subscales of a widely used psychological measurement instrument, the Eysenck
      Personality Questionnaire-Revised (EPQ-R), across gender. A bootstrapping
      methodology is employed which allows empirically derived standard errors to be
      calculated, and therefore tests of significance of difference to be computed. No
      significant differences were found in the reliability of the EPQ-R across sexes.

PMID- 10085552
TI  - Human cts18.1 gene: chromosomal localization and PH-domain analysis.
AB  - The human cts18.1 gene has high homology with the cytohesin gene family. By PCR
      analysis of a human monochromosomal somatic cell hybrid DNA panel, the cts18.1
      gene was localized to chromosome 19. Diversity values of synonymous and
      nonsynonymous substitutions indicate that negative selection has occurred in the
      pleckstrin-homology (PH) domain of the cytohesin gene family. The phylogenetic
      tree calculated by the neighbor-joining method suggests that cts18.1 and
      cytohesin-2 genes are more closely related to each other than either of them is
      to the CLM-2 gene in the analysis of cDNA of the PH domain.

PMID- 10085553
TI  - Subfamily divergence in the multigene family of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (rbcS) in Triticeae and its relatives.
AB  - To investigate genetic mechanisms acting on multigene family in plants, we
      analyzed sequence variation in the rbcS gene of 13 species of Triticeae and one
      species each of related tribes (Bromeae and Aveneae). A total of 36 rbcS genes
      were analyzed. Based on dimorphism in the length of intron, the rbcSs of
      investigated species were classified into two subfamilies A and B. The difference
      in intron length was caused by an indel of about 200 bp in the middle of the
      intron. The two subfamilies of rbcS were present in the three tribes, indicating
      that the divergence of rbcS subfamilies occurred before the split of these
      tribes. Generally, variation between the two subfamilies of rbcS was larger than
      that within subfamily, but these two measures were about the same at the tribe
      level. This result suggested that divergence of the subfamilies of rbcS occurred
      at about the same time of tribe diversification. The level of nucleotide
      variation in the exon region between subfamilies was reduced in the Triticeae,
      but clear change was not detected in the intron sequence. This result suggested
      that the exon sequences between subfamilies of rbcS were homogenized without
      affecting the intron sequence in the Triticeae lineage.

PMID- 10085554
TI  - Nucleotide changes in mitochondrial 16S rRNA gene from different mammalian cell
      lines.
AB  - The partial nucleotide sequences of mitochondrial 16S rRNA gene were analyzed in
      five rodent cell lines, prior to the analysis of mutation spectrum in the gene.
      Total DNA was isolated from V79 and CHO-K1 cell lines from Chinese hamster and
      murine cell lines, Balb Y SV and PCC4 AG Cap, and the 3' terminal regions
      including the peptidyl transferase domain which is the target for
      chloramphenicol, a selective inhibitor of mitochondrial protein synthesis, were
      amplified by polymerase chain reaction (PCR) using two sets of primers and
      directly sequenced. In Chinese hamster cells, C to T transition at one site was
      observed in CHO-K1, and either A was deleted at the sequence of AA in all three
      cell lines, relative to the V79-cell sequence registered in GenBank. One G to A
      transition mutation in heteroplasmic state was observed in mouse PCC4 AG Cap
      cells which have chloramphenicol resistant phenotype, whereas there was no change
      in the Balb Y SV cell line, relative to the L-cell sequence. These mutation sites
      were located outside the peptidyl transferase domain.

PMID- 10085555
TI  - Convergence of multilocus systems under weak epistasis or weak selection.
AB  - The convergence of multilocus systems under viability selection with constant
      fitnesses is investigated. Generations are discrete and nonoverlapping; the
      monoecious population mates at random. The number of multiallelic loci, the
      linkage map, dominance, and epistasis are arbitrary. It is proved that if
      epistasis or selection is sufficiently weak (and satisfies a certain
      nondegeneracy assumption whose genericity we establish), then there is always
      convergence to some equilibrium point. In particular, cycling cannot occur. The
      behavior of the mean fitness and some other aspects of the dynamics are also
      analyzed.

PMID- 10085556
TI  - The unfolding of an auditory illusion.

PMID- 10085557
TI  - The dementia dilemma.

PMID- 10085558
TI  - Cloning of animals and humans: what should the policy response be?

PMID- 10085559
TI  - Contesting consent: the challenge to compulsory neonatal screening for PKU.

PMID- 10085560
TI  - Reconditis: a malignant variety of obscurantism associated with pathological
      deficit of common sense.

PMID- 10085561
TI  - Strange tales of small men: homunculi in reproduction.

PMID- 10085562
TI  - Fate and effects of linear alkylbenzene sulphonates (LAS) in the terrestrial
      environment.
AB  - Linear alkylbenzene sulphonates (LAS) are a group of anionic surfactants,
      characterised by having both a hydrophobic and a hydrophilic group. LAS is one of
      the major ingredients of synthetic detergents and surfactants and is used world
      wide for both domestic and industrial applications. LAS is relatively rapidly
      aerobically degraded, but only very slowly or not at all degraded under anaerobic
      conditions. Therefore, LAS can be found in very high concentrations in most
      sewage sludge and enter the soil compartment as a result of sludge application.
      LAS can be found in elevated concentrations in soil immediately after sludge
      amendment, but a half-life of approximately 1-3 weeks will generally prevent
      accumulation in soil and biota. The concentration in soils that have not received
      sewage sludge recently, is generally less than 1 mg kg-1 and not more than 5 mg
      LAS kg-1. This is below the lowest concentration of LAS where effects have been
      observed in the laboratory. The laboratory data is in accordance with field
      studies using aqueous solutions of the sodium salt of LAS. However, observations
      of the ecological impact of sewage sludge applications or application of LAS
      spiked into sludge indicates a lower toxicity of LAS when applied in sludge. On
      the basis of the information reviewed in this paper, it is concluded that LAS can
      be found in high concentrations in sewage sludge, but that the relatively rapid
      aerobic degradation and the reduced bioavailability when applied via sludge, most
      likely will prevent LAS from posing a threat to terrestrial ecosystems on a long
      term basis.

PMID- 10085563
TI  - Dental lead levels in residents from industrial and suburban areas of Kuwait.
AB  - The present study describes lead concentrations in whole incisor teeth (non
      carious) of 216 Kuwaiti resident's aged 3-74, collected from industrial and
      suburban areas of Kuwait. The mean concentration of lead in all age groups (3-74)
      showed a significant correlation between both the sexes. Statistical analysis
      showed a significant correlation between lead levels of males compared with
      industrial and suburban areas. A similar correlation was also noted in the case
      of females supporting that industrial residents were more exposed to lead levels
      than those in suburban areas. A further significant correlation was noted between
      males and females of industrial and suburban areas which showed that males
      accumulate more lead concentration than females. A significant correlation was
      not observed when each age group was compared with that of the respective sexes
      representing industrial and suburban areas. However, a significant correlation
      was noted when lead levels in each age group was compared with that of the other
      age groups except in age groups ranging 35-42. The mean lead levels of 216 teeth
      were in the range 2.21-2.50 micrograms/g which is less than the range indicated
      by other investigators in the recent past.

PMID- 10085564
TI  - Spatial and seasonal variation in heavy metals in the sediments and biota of two
      adjacent estuaries, the Orwell and the Stour, in eastern England.
AB  - A study was made of the concentrations of the elements As, Cd, Cu, Hg, Mn, Ni, Pb
      and Zn in the sediments and biota of two adjacent estuaries, the Orwell and
      Stour, in eastern England. The Orwell Estuary, with its urbanized head, was more
      contaminated with heavy metals than the Stour Estuary. Generally, in both
      estuaries, concentrations of metals were highest towards the head and the mouth.
      Saltmarsh sediments accumulated higher concentrations of most metals than mudflat
      sediments. Metal concentrations in the biota showed marked interspecific
      differences; Mytilus edulis had higher concentrations of Cd, Littorina littorea
      higher concentrations of Cu and Mn and Arenicola marina higher concentrations of
      Hg. Invertebrates from the Orwell had higher metal concentrations than those from
      the Stour. Algae had generally lower levels of metals than invertebrates. Metal
      concentrations were greatest and more variable in the top 10 cm of sediment.
      Metals were at greatest concentrations in winter and lowest in summer in
      sediments, algae and invertebrates. Mercury concentration increased with size in
      the three invertebrate species studied, but Cd and Zn generally were at higher
      concentrations in younger animals. Comparisons of sediments with average shale
      values indicated anthropogenic enrichment with several metals but it was
      considered that only Pb, at some sites, and possibly Hg posed potential threats
      to the ecology of the estuaries.

PMID- 10085565
TI  - Monitoring metals in the vicinity of a municipal waste incinerator: temporal
      variation in soils and vegetation.
AB  - The aim of this study was to determine the temporal variation in the
      concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr),
      manganese (Mn), mercury (Hg), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl),
      vanadium (V) and zinc (Zn) in soil and vegetation near an old municipal solid
      waste incinerator (MSWI). In October 1997, 24 soil and 24 herbage samples were
      collected at the same sampling points in which samples were also taken in October
      1996. With the exception of an increase in the levels of Be and Ni, no
      significant differences in soils between both surveys were found; only Cr and V
      (decreases) and Hg (increase) showed significant variations in herbage samples
      during the last year. The concentrations of most elements in soil and vegetation
      samples collected near the MSWI are within the ranges previously reported for
      soil and vegetation in the vicinity of MSWIs.

PMID- 10085566
TI  - Quality assurance in analysis of cryogenically stored liver tissue specimens from
      the NIST National Biomonitoring Specimen Bank (NBSB).
AB  - Portions of liver tissue specimens originally stored in the National
      Biomonitoring Specimen Bank (NBSB) and analyzed between 1980 and 1987 were re
      analyzed in 1997 using instrumental neutron activation analysis (INAA) for the
      determination of 17 trace elements. Duplicate portions of each specimen had been
      stored at two different temperatures. The first was stored in a liquid nitrogen
      vapor-cooled freezer at -150 degrees C, standard NBSB storage conditions, and the
      other in an electric freezer maintained at -80 degrees C. Two portions of seven
      livers from each storage temperature were re-analyzed for this work. Results
      showed no changes in trace element content as a function of storage temperature,
      within the uncertainty of the method used. Results from these analyses agreed
      with results of initial analyses for most analytes in most sub-samples. Of the
      exceptions, five were due, in part, to an incorrect basis mass for the initial
      sub-specimen of one tissue, five with variable Zn results were attributed to
      difficulties in peak fitting for this element during INAA data processing, and
      the remaining were isolated differences discussed in this paper. Results of this
      work indicate that specimen storage and processing protocols are adequate to
      prevent noticeable contamination of specimens with trace elements, with the
      exception of Cr. Variability in Cr content was observed for the liver tissues
      which may have been caused by Cr contamination of the samples by the Teflon mill.
      Analyses of portions of Standard Reference Material (SRM) 1566a Oyster Tissue
      (certified in 1989) and SRM 1577a Bovine Liver (certified in 1982) were also
      included in this study for the purpose of quality control and to assess the
      stability of these freeze-dried powders that were stored at room temperature. No
      changes were observed in these materials.

PMID- 10085567
TI  - Capsella bursa-pastoris (L.) Medic. as a biomonitor of heavy metals.
AB  - Capsella bursa-pastoris (L.) Medic. (shepherd's purse) has been tested as a
      possible biomonitor of heavy metals in the city of Bradford, UK and compared with
      Poa annua L. (annual meadow-grass), a species with a similar ecology that had
      previously been studied for biomonitoring potential. Forty-two sites (urban
      roadside, urban, urban park, suburban and rural) in and around Bradford were
      investigated. Concentrations of Pb, Cd, Zn and Cu have been determined in soils
      and in washed and unwashed plant leaves. Differences between the washed and
      unwashed samples, reflecting airborne and soil entry routes, respectively, varied
      according to the metal pollutant. There were significant relationships between
      the heavy metal concentration in samples of surface soil (depth 0-10 cm) and
      washed leaves, the concentrations being greater with progressively increased
      urbanisation of the sites. Capsella bursa-pastoris has been found to be a useful
      biomonitor of the four heavy metals studied, and it may be a particularly useful
      species since it could monitor short-term changes in pollution in urban areas.

PMID- 10085568
TI  - Zinc in primary teeth from children in Norway.
AB  - Human primary teeth have been used as indicators of exposure to several heavy
      metals both in Norway and elsewhere. Local dentists in all 19 counties of Norway
      collected 2747 primary teeth during 1990-1994. Samples of tooth powder from
      whole, ground teeth were analyzed for zinc concentration by flame atomic
      absorption spectrophotometry. The overall geometrical mean was 144.5 micrograms
      of Zn/g of tooth substance (S.D. = 1.6). The result represents a small increase
      (5.2%) compared with a similar investigation in the 1970s. However, the mean zinc
      concentrations in the geographically matching parts of the two materials did not
      differ significantly. The variation in tooth zinc concentrations between the
      different counties declined from the 1970s to the 1990s. We found no correlation
      between the tooth zinc concentration and available environmental data on zinc in
      drinking-water, discharge of zinc from industrial point sources or population
      density in the same geographical areas. The zinc concentrations varied
      significantly with caries status, tooth type and root length. Few samples had a
      zinc concentration below 90 micrograms/g, indicating that most children consume
      sufficient zinc. Some very high values could not immediately be explained, but
      may be caused by contamination from zinc-containing dental restorations.

PMID- 10085569
TI  - The PM2.5 and PM10 particles in urban areas of Taiwan.
AB  - This study conducted an atmospheric aerosol sampling to measure the PM10
      (particles < 10 microns in aerodynamic diameter) and PM2.5 (particles < 2.5
      microns in aerodynamic diameter) mass concentrations from October 1996 to June
      1997 in northern (Taipei), central (Taichung) and southern (Kaohsiung), the three
      largest cities of Taiwan. Seventy-eight samples were obtained to measure the mass
      concentrations of PM10 and PM2.5 from nine sampling sites. According to those
      results, the PM10 mass concentrations in Taipei, Taichung and Kaohsiung were
      42.19, 60.99 and 77.10 micrograms/m3, respectively. The corresponding PM2.5 mass
      concentrations were 23.09, 39.97 and 48.47 micrograms/m3, respectively. The PM2.5
      fraction accounted for 61-67% of the PM10 mass in central and southern Taiwan,
      but was lower (54-59%) in northern Taiwan. Some samples in which the PM2.5
      fraction was overwhelmingly dominant could reach as high as 80-95% of the PM10
      mass. In addition, the PM2.5, PM10 levels and PM2.5/PM10-2.5 (particles with
      aerodynamic diameters ranging from 2.5 to 10 microns) ratios in metropolitan
      Taiwan significantly fluctuated from site-to-site and over time. Moreover,
      ambient daily PM2.5 and PM10-2.5 mass concentrations did not correlate well with
      each other at most of the sampling sites, indicated that they originated from
      different kinds of sources and emitted variedly over time.

PMID- 10085570
TI  - Risk assessment of a former military base contaminated with organoarsenic-based
      warfare agents: uptake of arsenic by terrestrial plants.
AB  - Organoarsenic-based chemical warfare agents (CWAs) such as the sternutators
      diphenylchloroarsine (CLARK I), diphenylcyanoarsine (CLARK II) or
      phenyldichloroarsine (PFIFFIKUS) still pose a notable risk in countries where
      former military bases that have stored these weapons have not yet been reclaimed.
      In fact, this is the case for many countries of Eastern Europe and the CIS. One
      of the most important military bases of the former Third Reich, the
      Heeresmunitionsanstalt I and II, is situated close to the German-Polish border at
      Loecknitz (Fig. 1). The German army stored and decanted different compounds of
      CWAs at this military base until 1945. When the Soviet Army destroyed the base in
      1946, large amounts of CWAs and other organoarsenic compounds polluted the soil.
      Today up to 250 g (!) of arsenic may be found in 1 kg of soil at some places in
      this area. Since 1991, a Government Working Group has been working on the risk
      assessment in order to define the scope of reclamation measures. This study
      investigates the contamination and the uptake of arsenic by plants because little
      is known about the bioavailability and metabolism of sternutators and their
      constituents. The total arsenic concentration of nine different species of
      terrestrial plants with at least six samples per species is presented. In spite
      of the considerable arsenic contamination of the soil (mean value 923 mg
      arsenic/kg soil) the plant contamination remained comparably low. The median
      value of arsenic contamination of the above-ground organs of velvet grass, Holcus
      lanatus, was 0.7 mg/kg dry wt. and the mean value was 4.3 mg/kg dry wt. due to
      some highly contaminated samples. The highest arsenic concentration registered
      was 26 mg/kg dry wt. in a sample of H. lanatus, which was most probably caused by
      soil particles adhering to the plant. The chemical structure of the arsenic
      compounds carried by the above-ground plant organs has been determined by gas
      chromatographic investigations and showed an uptake of triphenyl arsine by the
      plants.

PMID- 10085571
TI  - Investigation of absolute metal uptake efficiency from precipitation in moss.
AB  - Bioaccumulation of metals in moss was studied by the absolute method using a
      specially designed 'moss bag' technique. Bulk deposition was collected in open
      areas along with bulk deposition collected under moss. An absolute uptake
      efficiency of approximately 60% was obtained, which is in good agreement with the
      value obtained by a relative method. The absolute uptake efficiency varied
      between 0 and 92%, hence uptake of metals depends very strongly on
      microenvironmental conditions which can even cause leaching of metals from moss.
      The best retained elements were Pb, Ni, Cu and V, while Cd, Cr, Fe and Zn
      exhibited significantly lower uptake efficiencies. Manganese in all cases showed
      leaching of the element from moss.

PMID- 10085572
TI  - Apparent bioaccumulation of Mn derived from paper-mill effluent by the freshwater
      crayfish Cherax destructor--the role of Mn oxidising bacteria.
AB  - Bioaccumulation studies of wastewater from a thermo-mechanical paper mill using
      the freshwater crayfish (Cherax destructor) consistently demonstrated elevated
      levels of manganese. Most of the Mn appeared to be associated with the carapace
      of the animals. It is suggested that the elevated Mn levels are the result of Mn
      oxidising bacteria forming biofilms on the carapace of the crayfish followed by
      Mn oxide precipitation rather than active uptake of Mn by the crayfish.

PMID- 10085575
TI  - Delineation of conformational and structural features of the amikacin-Cu(II)
      complex in water solution by 13C-NMR spectroscopy.
AB  - The copper (II) complex of amikacin in water solution at pH 5.5 was investigated
      by 13C-NMR. The temperature dependence of spin-lattice relaxation rates was
      measured and fast exchange conditions were shown to apply. The motional
      correlation time of the complex was approximated by the pseudo-isotropic
      rotational correlation time of free amikacin in water solution (tau c = 0.17 ns
      at 300 K). Formation of a pseudo-tetrahedral 1:1 complex was demonstrated by
      relaxation rates analysis and also by UV-Vis spectrophotometry. Two amino
      nitrogens of amikacin, together with the amide nitrogen and the hydroxyl in the
      hydroxyl-aminopropyl carbonyl side chain, were assigned as the copper-binding
      sites and a model of the complex was built by using copper-carbon distances
      obtained by NMR analysis as input parameters.

PMID- 10085576
TI  - Spectroscopic investigation of phenolic groups ionization in the vipoxin
      neurotoxic phospholipase A2: comparison with the X-ray structure in the region of
      the tyrosyl residues.
AB  - The neurotoxin vipoxin is the major lethal component of the venom of Vipera
      ammodites meridionalis, the most toxic snake in Europe. It is a complex between a
      toxic phospholipase A2 (PLA2) and a non-toxic protein inhibitor (Inh). Tyrosyl
      residues are involved in the catalytic site (Tyr 52 and 73) and in the substrate
      binding (Tyr 22). Spectroscopic studies demonstrated differences in the
      ionization behavior of the various phenolic hydroxyl groups in the toxic PLA2.
      The tyrosyl side chains of the enzyme can be classified into three groups: (a)
      three phenolic hydroxyls are accessible to the solvent and titrate normally, with
      a pKeff = 10.45; (b) three residues are partially 'buried' and participate in
      hydrogen bonds with neighboring functional groups. They titrate anomalously with
      a pKeff = 12.17; (c) two tyrosines with a pKeff = 13.23 are deeply 'buried' in
      the hydrophobic interior of PLA2. They became accessible to the titrating agent
      only after alkaline denaturation of the protein molecule. The spectroscopic data
      are related to the X-ray structure of the vipoxin PLA2. The refined model was
      investigated in the region of the tyrosyl side chains. The accessible surface
      area of each tyrosyl residue and each phenolic hydroxyl group was calculated. A
      good correlation between the spectrophotometric and the crystallographic data was
      observed. The ionization behavior of the phenolic groups is explained by
      peculiarities of the protein three-dimensional structure and the participation of
      tyrosines in the catalytic site hydrogen bond network. Attempts are made to
      assign the calculated pKeff values to individual residues. The high degree of
      'exposure' on the protein surface of Tyr 22 and 75 is probably important for
      their function as parts of the substrate binding and pharmacological sites.

PMID- 10085577
TI  - The interaction of the nitrate anion with cytochrome c peroxidase: a 15N-NMR
      study.
AB  - The interaction of the nitrate anion with cytochrome c peroxidase has been
      demonstrated by using 15N-NMR spectroscopy. The results indicate that the nitrate
      anion binds to the protein in a specific binding site and are consistent with the
      hypothesis of an interaction of this small anion in the active cavity of the
      enzyme, possibly in the proximity of the distal histidine and the distal
      arginine.

PMID- 10085578
TI  - [Use of tempered, particle-reinforced aluminum horse shoes in sport horses under
      field conditions].
AB  - The use of handmade particulate reinforced alloy horseshoes (MMC metal matrix
      composites) was tested in a field study on 15 riding and draught horses. All
      horseshoes have been tempered after having been manually forged and tested
      concerning their surface imperfection. Forging temperature ranged between 350
      degrees and 420 degrees C. Horseshoes in series A consisted of particulate
      reinforced wrought alloy (22% Al2O3 in alloy matrix). 11 shoeing periods with a
      duration of mean = 49.7 days (sd = 13.6) were evaluated. Horseshoes in series B
      consisted of particulate reinforced foundry alloy (20% SiC in alloy matrix), 5
      shoeing periods were evaluated with a duration of mean = 45.4 days (sd = 7.9).
      Series C tested horseshoes made of particulated reinforced coextruded wrought
      alloy evaluating 6 shoeing periods with a duration of mean = 49.2 days (sd =
      18.7). Service of the tempered particulate reinforced alloy horseshoes was
      significantly higher compared to untempered alloy horseshoes. Mechanical and
      forging properties of tempered particulate reinforced alloy are satisfactory.
      Service is only suitable for riding horses but not for draught horses.

PMID- 10085579
TI  - [Vaccination of ostriches (Struthio camelus, Linnaeus, 1758) against Newcastle
      disease: evidence for vaccine compatibility and seroconversion after vaccinations
      using the hemagglutination inhibition and virus neutralization tests].
AB  - Newcastle disease (ND) remains to be the worldwide most important infectious
      disease of poultry. This epizootic is in Germany and many other countries a
      notifiable disease. Prophylactic vaccination is the major tool for the control of
      ND in poultry and other birds. Eighty-three ostriches (Struthio camelus) which
      were kept on farms in Germany were checked for the presence of NDV-specific
      antibodies. Some of these birds are said to be vaccinated against Newcastle
      disease. Only some of these ostriches contained antibodies which were measurable
      in haemagglutination inhibition and virus neutralisation tests. Twenty-three
      previously unvaccinated ostriches were vaccinated with commercially available
      vaccines. Both the LaSota live and inactivated oil emulsion vaccines were well
      tolerated following conjunctival or subcutaneous application, respectively.
      Neither local nor systemic side reactions were observed. After the vaccinations
      high antibody titres were detected in hemagglutination inhibition and virus
      neutralisation tests. A strong correlation between both established methods (r =
      0.92; < 0.001) were noted.

PMID- 10085580
TI  - Update on footrot in south-west Germany.
AB  - 82 Dichelobacter nodosus strains isolated from 9 footrot affected sheep flocks in
      south west Germany were serotyped and tested for virulence. Serovar B was present
      in all flocks, representing 64.4% of all isolated D. nodosus field strains. Other
      serovares found were type A, C, E, G and H. Virulent strains were identified in 5
      flocks, while intermediate strains were isolated from all 9 flocks. All
      serological untypeable strains proved to be avirulent. Based on these
      epidemiological findings the use of currently available commercial footrot
      vaccines is appropriate in south west German sheep populations.

PMID- 10085581
TI  - Effect of pesticide water pollution on some haematological, biochemical and
      immunological parameters in Tilapia nilotica fish.
AB  - Nine groups of Tilapia nilotica fish each consisting of 50 fish were used to
      assess the effect of pesticides on the haematological, biochemical and
      immunological parameters in fish. Four groups were injected with 0.05 ml of
      Staphylococcus aureus antigen plus complete Freund's adjuvant, the first group
      (G1) was exposed to lindane treatment, the second (G2) was exposed to dialdrin,
      the third (G3) was exposed to diazinon and the forth group (G4) was exposed to
      malathion. Four other groups were not immunized, but injected with the adjuvant
      and exposed to the pesticides, the fifth group (G5) was exposed to lindane, the
      sixth (G6) was exposed to dialdrin, the seventh (G7) was exposed to diazinon and
      the eighth group (G8) was exposed to malathion. The ninth group (G9) was exposed
      to water without any pesticide treatment and served as controls. Both vaccinated
      and non-vaccinated groups were exposed to 1/10 LC50 of the tested pesticides for
      30 days. The results revealed that the mean total RBCs, WBCs counts, PCV, Hb,
      MCV, MCH, MCHC values were lower in vaccinated groups than in the groups exposed
      to the tested pesticides. The total protein, globulin and serum enzymes ALAT;
      ASAT values as well as macrophage phagocytic index and antibody titer were lower
      in vaccinated as compared to the non-vaccinated groups.

PMID- 10085582
TI  - Therapeutic effects of some antihaematozoal drugs against Haemoproteus columbae
      in domestic pigeons.
AB  - Three antihaematozoal drugs were tested for the treatment of pigeons naturally
      infected with Haemoproteus columbae. Butalex (Buparvaquone) was found effective
      against the parasite either by using the recommended dose (R. D.) or the double
      (D. D.) dosis. The R. D. of Berenil (Diminazene aceturate) was not effective
      while the D. D. reduced the number of gametocytes circulating in the infected
      blood. Triquine was found very toxic to the pigeons both the R. D. and the D. D.

PMID- 10085583
TI  - [Diagnosis of Clostridium botulinum intoxication].

PMID- 10085584
TI  - [Botulism in horses].

PMID- 10085585
TI  - [Clinical aspects of botulism in cattle].

PMID- 10085586
TI  - [Molecular biology of neurosecretion and its inhibition by botulinum and tetanus
      toxins].

PMID- 10085587
TI  - [Stomach ulcers in swine from the clinical viewpoint].

PMID- 10085588
TI  - [In vitro studies of the pathogenesis of ulcers in the pars proventricularis of
      swine].

PMID- 10085589
TI  - [Skeletal development disorders and nutrition--a clinical study].

PMID- 10085590
TI  - [New plate osteosynthesis methods. No-contact plate for limb fractures of dogs].

PMID- 10085591
TI  - [Skeletal diseases in young dogs: nutritionally determined pathogenesis].

PMID- 10085592
TI  - [Meeting report: recent advances of research on antinutritional factors in
      legumes and rapeseed].

PMID- 10085593
TI  - [Hereditary hemochromatosis: biochemical and genetic diagnosis].

PMID- 10085594
TI  - [Wilson's diseases].

PMID- 10085595
TI  - [Metabolic hepatopathies in infancy. Alpha 1-antitrypsin deficiency].

PMID- 10085596
TI  - [Nonalcoholic steatohepatitis].

PMID- 10085597
TI  - [Hepatic biopsy in storage hepatic diseases].

PMID- 10085598
TI  - [Imaging tests for the diagnosis of metabolic diseases].

PMID- 10085599
TI  - [Indications and results of liver transplant in type I familial amyloid
      polyneuropathy].

PMID- 10085600
TI  - [Hepatopathies in porphyria].

PMID- 10085601
TI  - [Heterotopic pregnancy following ovulation induction by clomiphene citrate and
      prednisone. Report of a case].
AB  - Heterotopic pregnancy (HP) is a very rare pathologic event. The incidence of
      ectopic pregnancy has increased as the consequence of assisted reproduction and
      the wider use of ovulation induction agents. The diagnosis of HP is frequently
      done not as earlier as it should be, and it has serious repercussions. The
      concept of screening, to find relevant rise factors and the correct diagnosis of
      HP should be pursued as early as possible. In this report we describe an unusual
      case of a female patient with therapeutic failure to clomiphene citrate. She was
      treated with two cycles of combined clomiphene citrate and prednisone, and
      ovulation induction assent. The after she developed HP. Overall, we conclude that
      the possible association observed could be an accident. The land of investigation
      is open, to fill cover. The holes on understanding that we still have.

PMID- 10085602
TI  - [Laparoscopy and hysteroscopy in Mullerian duct malformations: usefulness and
      reproductive results].
AB  - Determine the type and the possibility of corrective surgery, reproductive
      results of infertility patients with Mullerian malformations. The clinic and the
      laparoscopic and hysteroscopic evaluation were performed to 40 patients with
      Mullerian anomalies and infertility history analyzing the reproductive results.
      The uterine septum was present in 23/40 patients (57.5%), bicornual uterus in
      6/40 (15%), didelfus uterus 5/40 (12.5%), arcuate uterus 4/40 (10%), unicorn
      uterus 2/40 (5%). After septum resection we had 13 pregnancies (56.5%). 2
      abortions, 4 already delivered and 7 continue normal evolution with on twin case.
      Strassman metroplasty by laparotomy was performed in 4 cases of bicornual uterus
      achieving pregnancy in two cases. In one didelfus uterus, a salpingoclasy of the
      smaller horn was done as an alternative. Of the arcuated uterus, the small septum
      was removed. Of the unicorn uterus, one pregnancy was lost in the first trimester
      and the other one reach the term date. Our data show that the endoscopic
      procedures can perform the correct diagnosis of the Mullerian anomalies and of
      course the best surgical treatment improving the fertility rates.

PMID- 10085603
TI  - [Trends in cesarean section procedures in three locations of the Mexican Social
      Security Institute Medical Services during the period 1981-1995].
AB  - The trend of the cesarean section in three setting of the Instituto Mexicano del
      Seguro Social (IMSS); the local: Hospital Gineco-pediatrico No. 2, in Los Mochis,
      Sinaloa, was determined the state's: included all of the medical units of IMSS in
      the state of Sinaloa and the national, which included all of the medical units of
      IMSS in the country. It was an analytic, retrospective study medical units of
      IMSS cesarean deliveries in the three setting of IMSS, from 1981 to 1995. SOURCE
      OF INFORMATION: State Committee of the Information Processing of the State of
      Sinaloa retrospective measurement of the total of deliveries and cesarean
      sections to calculate frequency of this event for each year and setting. Lineal
      regress analysis was made to determine trend of cesarean sections and correlation
      coefficient (r). RESULTS: Local frequency: 24.3 +/- 6.1%, range 14.7-33.6%;
      state's: 21.6 +/- 5.8%, range 13.2-30.3, national 24.4 +/- 5.5%, range 16.6-33.6;
      r per setting: local: +0.98 (Cl 95% 0.8793 = 0.99), state's +0.99 (Cl 95% 0.94
      0.99) and national: +0.99 (Cl 95% 0.95-1.0). Positive trend in performance of
      cesarean sections in the three setting during the period of study; if no
      intervention on the matter at IMSS, the national trend will reach 39.2% in the
      2000 year, state's: 37.4% and the local: 39.4%.

PMID- 10085604
TI  - [Sacro-colpoplexy using mersilene: report of 12 cases at the General Hospital
      Zone 7, Monclova, Coahuila].
AB  - The purpose of this study was to describe our experience to be realizing Sacral
      colpopexia in patients with prolapso of cupola from March 1991 to August 1996 and
      to compare our results with the written in the National and International
      literature, cause at least in our country the reports and the number of patients
      that are included in thus kind of surgery are fex, even in hospitals with great
      concentration. Twelve women were attended which age were average 52 years old,
      multiparity in 83.3% of these cases and all of them with the story of
      hysterectomy. In the 58.3% the symptoms produced by the prolapse were presented
      was sensation of rare body and to give up the sexual activity in the patients
      that got in before of the prolapse was emerged. In 5 patients (41.6%) also this
      symptomatology was accompanied by incontinence urinary of stress because of were
      demonstrated in them the debility of the anterior vaginal wall and for this
      reason was realized Sacral colpopexy plus operation of Burch at the same surgical
      time. A mersilene No. 5 material was used in order to set the vaginal cupola to
      the anterior ligament of the sacral an a "bridge" of the additional reinforce
      with the same material. Were not emerged transoperatory complications. The
      following of our patients after surgery had been from 6 month to 6 years
      (depending on the year in which was the surgery) and sexual activity reset in the
      patients has been identified got it before the prolapse, and by the other side a
      new prolapse is not presented in the patients of the study. We establishes
      surgical preventive rules to avoid the prolapse of cupola in patients that are
      emerged to hysterectomy, vaginal or abdominal.

PMID- 10085605
TI  - [Clinical use of a quadruple biochemical marker in the prediction of obstetric
      complications].
AB  - The objective was to evaluate the association of an abnormal second trimester
      prenatal biochemical screening with the subsecuent development of pregnancy
      complications in women carrying chromosomally normal fetuses. A prospective study
      of 123 pregnant patients was performed. Specimens were assayed for alpha
      fetoprotein, unconjugated estriol, free alpha hCG, and total hCG. The study
      included the evaluation of the mean and standard desviation as well as multiple
      of the median. Six women (4.6%) had positive results. The frequency of pregnancy
      complications in this group was 33.3%, while in the group with negative screening
      was 11.1%. As conclusion, positive four marker screening is associated with a
      adverse pregnancy evolution. However the usefulness of four marker screening for
      to predict pregnancy complications needs more investigations.

PMID- 10085606
TI  - [Presence of fetal fibronectin in cervico-vaginal secretion as predictor of
      premature labor].
AB  - The objective of this article is to correlate a new biochemical method called
      fetal fibronectin (fFN) found in cervico-vaginal secretions (CVS) in pregnant
      woman with the presence or not of preterm labor. In this paper the patients
      studied had pregnancies of 24 up to 37 weeks of pregnancy. The were free of
      symptoms and without risk factors for preterm labor. The cervico-vaginal specimen
      was taken with special equipment designed for this purpose (Adeza Biomedical
      Collection Kit). The laboratory processed this for immunoassay. A positive fFN
      was considered above 0.05 microgram/dl. There were 263 patients enrolled for this
      study. Of these 232 had fFN negative (89%) and 31 were positive (12%). The weeks
      of gestation at birth were 38.6 for the negative group and 34.4 for the positive
      group (p < 0.0001). Only 5 neonates from the negative group were born before 37
      weeks of gestation (2.2%) and in the positive fFN group this occurred in 22 case
      (71%) (p < 0.0001). The average weight at birth for the negative fibronectin
      group was 3152 g. for the positive group (p < 0.0001). The neonatal morbidity was
      more frequent and respiratory distress syndrome was more severe in the positive
      fibronectin group in comparison with the negative fFN with a significant p. The
      same tendency was observe with the Apgar score < 7 at 1 and 5 minutes (more
      frequent in the positive group) (p < 0.0001). The was one neonatal death in the
      negative group (0.43%) and 5 in the positive group (16%) p = 0.0001. The
      sensibility and positive predicitive value of positive fFN for the prediction of
      preterm labor was 81.4 and 71 respectively and the specificity and negative
      predictive value for negative fFN was 96.1 and 97.8. Finally the RR for
      prematurity when the fFN was positive on SCV was 32.9. The presence fFN in
      cervical-vaginal secretion between 24 and 37 weeks of gestation seems to be a
      good indicator of preterm labor. In this study positive results correlate with
      less weeks of pregnancy and lees weight at birth. Also with higher with more
      morbidity and mortality. These findings give the obstetrician a better chance of
      an opportune diagnosis with adequate treatment and improve perinatal results.

PMID- 10085607
TI  - [Nitric oxide as a regulator of hemodynamic changes in pregnancy].
AB  - Nitric oxide (.NO) produced by the majority of animal cells, has been considered
      a second messenger, since it is the result of a transduction process induced by a
      first stimulus. Biochemically, .NO is produced during the conversion of L
      arginine to L-citruline by a reaction catalyzed by the enzyme nitric oxide
      synthetase. Two ixoenzymes have been characterized from this enzyme: a
      constitutive isoenzyme activated by hormones produced by the endothelial cells
      and acting on smooth muscle relaxing properties and the other, an inducible
      isoenzyme whose synthesis is stimulated by cytokines, and produced by
      macrophages. As pregnancy progresses, the concentrations of .NO, its metabolites,
      nitrates and nitrites, cGMP and the synthesizing enzyme, nitric oxide synthetase,
      increase parallelly until reaching a maximum peak before birth. It is considered
      that .NO is the molecule that maintains the typical vasodilated tone during
      pregnancy. During preeclampsia, this free radical, as well as its metabolites are
      found to be significantly decreased, in addition, the administration of .NO
      donors or of the precursor of L-arginine reverts the vascular abnormalities of
      this condition. The mechanism of action behind .NO on the vascular endothelium is
      by its stimulating effect on the enzyme cyclase guanilate, causing an increase in
      cGMP concentration and the relaxation of the smooth muscle. The nitric oxide
      generates by macrophages acts as a defense mechanism when linked with other
      radicals as the superoxide anion (O2).

PMID- 10085608
TI  - [Osseous metaplasia of the endometrium as a cause of infertility. Hysteroscopic
      approach].
AB  - The osseous metaplasia of the endometrium is very rare cause of infertility. The
      hysteroscopic approach is a effective method to recover the fertility in most of
      the cases in a short period. The case of a infertile woman who was previous
      studied and has indications for laparoscopic and hysteroscopic approach. The
      infertility workup showed a intracavitary calcification on ultrasonography.
      During the surgery, the diagnosis of endometriosis and osseous metaplasia of the
      endometrium were done and treated with histologic confirmation. The patient
      conceived in her second spontaneous cycle. The hysteroscopy is the first approach
      in the treatment and should be doing with laparoscopy for the detection of other
      causes of infertility.

PMID- 10085609
TI  - Outline of sport injuries in the V World Youth Championship for FIFA Cup in Saudi
      Arabia.
AB  - The V World Youth Championship for FIFA Cup was held for the first time in Saudi
      Arabia from 16-2-89 till 3-3-89. Sports injuries at this competitions was
      reported from the city of Jeddah, Saudi Arabia with eight matches taking place at
      different days. Out of 176 soccer players from group C (Brazil, Germany DR, Mali
      and USA) who participated in this competition, only six were injured and 7
      injuries were noted with an incidence of 3.98% (n = 7/176). Lower limb injuries
      predominated (ankle sprain: 28.57%; tibia fracture: 14.29%), whereas head,
      facial, radius and rib injuries had equal rates (14.29%). Also, fractures
      predominated (42.86%) due to the aggressive attitudes. Concussion (14.29%) and
      cut wound (14.29%) were less common. High skills, good physical fitness,
      compliance of rules and regulations, strict surveillance of violence and
      misbehaviour by the FIFA cup organizing team and allied offices led to the well
      performance, safer environment and low incidence of sports injuries.

PMID- 10085610
TI  - Study of 'at risk' factors in rural under five children.
AB  - 1. In the present hospital based cross sectional study, 64.97% under five
      children in rural area were found to be 'at risk'. 2. The most common 'at risk'
      factor found in these under five children was weight below 70% of the reference
      (39.1%) followed by acute gastroenteritis and respiratory infections (19.3%),
      spacing of less than 2 years (13.2%) and working mothers where the child was
      being looked after by a substitute (12.2%). 3. More than one 'at risk' factors
      were found in 43 (21.8%) children. 4. Statistically significant association was
      found between 'at risk' children and illiteracy and poverty.

PMID- 10085611
TI  - Chromogenic agar for rapid presumptive identification of yeast species:--a
      preliminary report.
AB  - A chromogenic medium for the rapid presumptive identification of yeasts was
      devised and studied. The medium was found to be effective in differentiating the
      yeast species studied on the basis of colony colour. With further modification
      the medium can be used as a primary isolation medium.

PMID- 10085612
TI  - Transthoracic needle biopsy in the diagnosis of pulmonary lesions.
AB  - Transthoracic needle biopsy therefore proved to be a minor, inexpensive and safe
      procedure, which with simple technique permits a direct approach to all kinds of
      localized pulmonary lesions with a high degree of accuracy.

PMID- 10085613
TI  - Nosocomial infection in gun-shot [correction of gut-shot] injury patient: a case
      report.

PMID- 10085614
TI  - Catamenial hemoptysis--a case report.
AB  - Thoracic endometriosis is rare. Its associated clinical syndromes should be
      considered in menstruating women with pneumothorax or hemoptysis. The
      availability of chest CT scanning and danazol provide new technique in diagnosis
      and therapy.

PMID- 10085615
TI  - Emerging and re-emerging infectious diseases.
AB  - A number of "new" infections are emerging in our midst and the medical
      practitioners should be aware of these. Suspected cases should be urgently
      investigated and treated to prevent further spread.

PMID- 10085616
TI  - Prevention of E.N.T. diseases.
AB  - World Health Organization has announced 'HEALTH FOR ALL BY YEAR 2000'.
      Unfortunately the emphasis at present is only on early diagnosis of a disease and
      its treatment. The modern investigations and treatment has become very costly
      which a poor man cannot afford. Preventive medicine is less costly. The
      developing countries have many socio-economic problems of population explosion,
      poverty, ignorance, illiteracy, shifting of population from rural to urban areas
      for employment and traffic jams in cities. Rapid industrialization has resulted
      in indiscriminate cutting of trees and forests and increasing pollution. Under
      the present circumstances one wonders whether it would be possible to achieve the
      WHO's object of health for all or will it remain a dream! The role of 'Yoga and
      Meditation' and vegetarian diet has been recognised world over for maintenance of
      normal physical and mental health; these help to lessen mental tension in the
      present competitive world full of stress and strain for all of us. 3-4% of people
      in the world avail the beneficial effects of alternative system of medicine is
      complete as each has its own merits and limitations. Hence our aim should be to
      choose an integrated system of medicine which would help in preventing diseases
      and treat them early by a safe and effective procedure. In the present political
      situation in our country none of the parties have announced any definite
      programme for population control, through it is a grave problem. We will not be
      able to fulfil our object of reaching our target of Health for all without strict
      population control major. Unless this programme is undertaken seriously as a
      priority in a co-ordinated disciplined manner by all of us and completed in a
      given period of time, the younger generation will not forgive us. We hope that as
      true citizens of India we will not spare any efforts on our part in attaining
      this objective for a bright future.

PMID- 10085617
TI  - Study of head injury victims in fatal road traffic accidents in Delhi.
AB  - The study revealed 31% were the victims of Head injury injury in this part of
      Delhi in vehicular accidents. Although majority of the fatalities were on the
      spot quite a number of such victims survived for a varied period. A multipronged
      approach including the preventive and curative measures for this man-made
      calamity is the need of the hour. Amongst various preventive measure are wearing
      helmet be made compulsory for both the driver and pillion riders of two-wheelers,
      development of a safe traffic sense amongst the road users. Traffic Police should
      be honest, exemplary punishment for the reckless driver, decongestion of Delhi
      roads etc. The curative measures are facilities of CT scanners and neurosurgeons
      in all the major hospitals, provision of first-aid in the PCR (Police control
      room) vans, to institute immediate treatment to the victim without waiting for
      the medico-legal formalities, opening of more fully equipped Accident and trauma
      centres. It is high time the concerned authorities gave some serious thought
      towards this avoidable epidemic on Delhi roads.

PMID- 10085618
TI  - Malaria immunity: an overview on B cell responses and assays for detection of
      humoral immune responses.

PMID- 10085619
TI  - Serum malondialdehyde levels in Indian women.
AB  - Mean MDA level in the fifty women was 3.41 +/- 0.75 nmol/ml [table: see text]

PMID- 10085620
TI  - Germ cell tumour of testis.
AB  - Germ cell tumour, though rare, represents most common malignancy among young men
      aged between 15 to 35 years. In 1990's dramatic improvement has taken place in
      survival rate of testicular tumours (from 10% in 1970's and 90% in 1990's). This
      has been possible because of effective diagnostic techniques, accurate monitoring
      with biological markers and use of effective platinum based combination
      chemotherapy in its management. The most significant improvement in survival rate
      has occurred in advanced stage germ-cell tumours. Seminomas are sensitive to
      radiation therapy and NSGCT (Non Seminomatous Germ Cell Tumours). are effectively
      treated by combination chemotherapy of 3 drugs of which Bleomycin is most
      expensive and many patient can not afford it and so compliance is poor. In the
      present series we have tried only 2 drug regimen consisting of Platinum and
      Etoposide (PE). Since January 1992 to December 1994, 40 cases of testicular
      tumours were treated. 16 cases received PEB regimen and 24 cases were treated by
      PE regimen of which only 6 cases in the former and 20 cases in the later group
      completed the scheduled course. Patients were given 6 cycles of PE regimen (inj.
      Platinum 20 mg/m2 D1-D5, VP-16 (ETOPOSIDE), 100 MG/M2 1.V. D1-D5) repeated every
      three weeks. Final evaluation was done in June 1996. 17/20 (85%) patients on PE
      regiment exhibited complete regression of the disease by the end of June 1996, I
      was lost to follow up, and 2 of them had the disease in progressive stage and
      were considered for another regimen. 18 months disease free survival was 85%.
      Table I. Royal Marsden Staging System Stage I: Disease econfined to testes Stage
      II: Intradiaphragmatic node involvement A: Less than 2 cm B: 2-5 cm C: Greater
      than 5 cm Stage III: Supradiaphragmatic node involvement Stage IV: Extralymphatic
      disease Lung, Liver, Bone etc.

PMID- 10085621
TI  - Gastric teratoma in an infant--a case report.
AB  - Gastric teratoma is an extremely rare tumour. We report a gastric teratoma in a
      four month old male infant who presented with a large abdominal mass. There is no
      evidence of recurrence 1 1/2 years after the tumour was excised. Our case is an
      addition to the few cases reported in the World literature.

PMID- 10085622
TI  - Lead poisoning in a schizophrenic.

PMID- 10085623
TI  - A global initiative for the elimination of avoidable blindness.

PMID- 10085624
TI  - Idiopathic central serous chorioretinopathy.
AB  - Idiopathic central serous chorioretinopathy (ICSC) is usually seen in young males
      with Type A personality. Clinical evaluation of the macula with fundoscopy and
      biomicroscopy, coupled with fluorescein angiography establishes the diagnosis.
      Indocyanine green angiographic studies have reinformed that the basic pathology
      lies in choriocapillaries and retinal pigment epithelium. Most of the ICSC
      resolve completely in four months, and some of them could resolve early with
      direct photocoagulation of the leaking site. Oral steroids have no role, and
      could even cause an adverse reaction.

PMID- 10085625
TI  - Management of phacolytic glaucoma: experience of 135 cases.
AB  - We retrospectively analyzed 135 eyes with phacolytic glaucoma. A trabeculectomy
      was added to standard cataract surgery if symptoms endured for more than seven
      days, or if preoperative control of intraocular pressure (IOP) with maximal
      medical treatment was inadequate. In the early postoperative period, IOP was
      significantly lower in the combined surgery group (89 eyes) compared to the
      cataract surgery group (46 eyes) (p < 0.001). At 6 months there was no difference
      in IOP or visual acuity between the two groups. There were no serious
      complications related to trabeculectomy. It is reasonable to conclude that in
      eyes with a long duration of phacolytic glaucoma, addition of a trabeculectomy to
      cataract surgery is safe, prevents postoperative rise in intraocular pressure and
      decreases the need for systemic hypotensive medications. A randomized trial is on
      to further address this question.

PMID- 10085626
TI  - Central corneal endothelial guttae and age-related macular degeneration: is there
      an association?
AB  - The similarities between the corneal endothelium and retinal pigment epithelium
      in terms of their embryology, barrier function and predilection to age-related
      degeneration prompted this investigation into a possible association between
      central corneal guttae (CCG) and age-related macular degeneration (ARMD). 50
      patients with clinically significant CCG were prospectively evaluated for the
      presence of ARMD. 51 age-matched patients attending for unrelated ailments who
      did not have CCG were also evaluated for the presence of drusen and other signs
      of ARMD. Of the 50 patients with CCG, 23 had bilateral ARMD and 4 had unilateral
      ARMD. In the control group, 9 patients had bilateral and 4 had unilateral ARMD.
      There was significant difference in the prevalence of ARMD between patients with
      CCG and those with no CCG (p = 0.017 and p < 0.001 for right and left eyes
      respectively). We found an association between CCG and ARMD. The presence of CCG
      in a patient may imply increased risk for the presence of ARMD. In a patient with
      CCG requiring cataract or corneal surgery, the successful outcome may be
      compromised by the presence of ARMD.

PMID- 10085627
TI  - Causes of corneal graft failure in India.
AB  - The success of corneal grafting in visual rehabilitation of the corneal blind in
      India depends on survival of the grafts. Understanding the causes of graft
      failure may help reduce the risk of failure. We studied these causes in a series
      of 638 graft failures at our institution. Multivariate logistic regression
      analysis was used to evaluate the association of particular causes of graft
      failure with indications for grafting, socioeconomic status, age, sex, host
      corneal vascularization, donor corneal quality, and experience of surgeon. The
      major causes of graft failure were allograft rejection (29.2%), increased
      intraocular pressure (16.9%), infection excluding endophthalmitis (15.4%), and
      surface problems (12.7%). The odds of infection causing graft failure were
      significantly higher in patients of lower socioeconomic status (odds ratio 2.45,
      95% CI 1.45-4.15). Surface problems as a cause of graft failure was significantly
      associated with grafts done for corneal scarring or for regrafts (odds ratio
      3.36, 95% CI 1.80-6.30). Increased intraocular pressure as a cause of graft
      failure had significant association with grafts done for aphakic or pseudophakic
      bullous keratopathy, congenital conditions or glaucoma, or regrafts (odds ratio
      2.19, 95% CI 1.25-3.84). Corneal dystrophy was the indication for grafting in 12
      of the 13 cases of graft failure due to recurrence of host disease. Surface
      problems, increased intraocular pressure, and infection are modifiable risk
      factors that are more likely to cause graft failure in certain categories of
      patients in India. Knowledge about these associations can be helpful in looking
      for and aggressively treating these modifiable risk factors in the at-risk
      categories of corneal graft patients. This can possibly reduce the chance of
      graft failure.

PMID- 10085628
TI  - Ultrasonic characterisation of malignant melanoma of choroid.
AB  - An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in
      order to differentiate histological subtypes of malignant melanoma. To obtain the
      backscattering coefficient for the tissues, we used a broadband focussed
      transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz.
      Experimental measurement of backscattering coefficient and attenuation
      coefficient at various frequencies was done by substitution techniques. The
      backscattering coefficient, scatterer size, and root mean square velocity
      fluctuation were derived by the numerical method, while the attenuation
      coefficient at 1 MHz was derived from attenuation coefficient at different
      frequencies. This study revealed that backscattering coefficient and attenuation
      coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle
      cell type compared to the mixed cell type of malignant melanoma. Particularly,
      the scatterer size was significantly higher in the spindle cell group (p = 0.013)
      in contrast to the mixed cell type. Spindle cells have uniform and compact
      histological pattern which contributes to an increase in scatterer size and root
      mean square velocity fluctuation. The ultrasonically obtained parameters have
      been shown to have a good correlation with the histology of malignant melanoma.

PMID- 10085629
TI  - Human lens epithelial layer in cortical cataract.
AB  - Normal and cataractous human eye lenses were studied by morphology and protein
      analysis. A marked decrease in protein sulfhydryl (PSH) and nonprotein sulfhydryl
      (NSPH) was observed in nuclear and cortical cataractous epithelia. Moreover,
      decrease in PSH contents and an increase in insoluble proteins were found to be
      correlated only in cortical cataractous epithelium which is also accompanied by
      various morphological abnormalities. In nuclear cataractous epithelium, however,
      there was very little insolubilisation of proteins. The epithelial morphology in
      nuclear cataracts was almost similar to normal lens epithelium. Hence, it is
      assumed that the protein insolubilisation and various morphological abnormalities
      are characteristics of cortical cataractous epithelium. This leads us to believe
      that opacification in cortical cataract might initiate in the epithelial layer.

PMID- 10085630
TI  - Computers in ophthalmology practice.
AB  - Computers are already in widespread use in medical practice throughout the world
      and their utility and popularity is increasing day by day. While future
      generations of medical professionals will be computer literate with a
      corresponding increase in use of computers in medical practice, the current
      generation finds itself in a dilemma of how best to adapt to the fast-evolving
      world of information technology. In addition to practice management, information
      technology has already had a substantial impact on diagnostic medicine,
      especially in imaging techniques and maintenance of medical records. This
      information technology is now poised to make a big impact on the way we deliver
      medical care in India. Ophthalmology is no exception to this, but at present very
      few practices are either fully or partially computerized. This article provides a
      practical account of the uses and advantages of computers in ophthalmic practice,
      as well as a step-by-step approach to the optimal utilization of available
      computer technology.

PMID- 10085631
TI  - Economic burden of blindness in India.
AB  - Economic analysis is one way to determine the allocation of scarce resources for
      health-care programs. The initial step in this process is to estimate in economic
      terms the burden of diseases and the benefit from interventions for prevention
      and treatment of these diseases. In this paper, the direct and indirect economic
      loss due to blindness in India is calculated on the basis of certain assumptions.
      The cost of treating cataract blindness in India is estimated at current prices.
      The economic burden of blindness in India for the year 1997 based on our
      assumptions is Rs. 159 billion (US$ 4.4 billion), and the cumulative loss over
      lifetime of the blind is Rs. 2,787 billion (US$ 77.4 billion). Childhood
      blindness accounts for 28.7% of this lifetime loss. The cost of treating all
      cases of cataract blindness in India is Rs. 5.3 billion (US$ 0.15 billion).
      Similar estimates for causes of blindness other than cataract have to be made in
      order to develop a comprehensive approach to deal with blindness in India.

PMID- 10085632
TI  - Contaminated Irrigasol solution.

PMID- 10085633
TI  - Early re-establishment of blood aqueous barrier after phacoemulsification.

PMID- 10085634
TI  - Efficacy of paraformaldehyde tablets in sterilization of polyvinyl-chloride
      tubing.

PMID- 10085635
TI  - Optometry and eye care in India.

PMID- 10085636
TI  - Immunodiagnosis of human hydatid disease.
AB  - A study was undertaken to evaluate the efficacy of Enzyme Linked Immunosorbent
      Assay using locally prepared antigens for immunodiagnosis of human hydatid
      disease. A total of 90 cases clinically suspected to be suffering from hydatid
      disease and 100 controls matched for age and sex were included in the study. Two
      types of ELISA were performed on detected specific antihydatid antibodies
      belonging to IgG/IgM/IgA classes and other type detected IgE class of antibodies.
      Antigen prepared from the human hydatid fluid was found to be unsuitable for
      diagnosis as it contained host proteins i.e. IgG. Sheep hydatid fluid obtained
      from the fertile hydatid cyst was used to prepare and standardize the antigen.
      ELISA test to detect anti hydatid antibodies belonging to either IgG, IgM and or
      IgA was found to be highly specific (98 per cent) in surgically confirmed hydatid
      disease and was negative in all the controls. The results of the study indicate
      that ELISA along with casoni test may provide the best results in diagnosis of
      hydatid disease.

PMID- 10085637
TI  - Epidemiology of HIV and AIDS in Bahrain.
AB  - Between 1986 and 1996, 378 HIV cases were identified in Bahrain, of whom 51% were
      foreign nationals. Intravenous drug abuse was a major risk factor (38.8%) among
      Bahraini nationals, while transmission through sexual contact was more common
      (45.7%) among foreigners. Other well known risk factors were also represented in
      the two communities. The male to female ratio for the two communities were very
      different with 10:1 for nationals compared to 1:1.4 for foreigners. Among the
      AIDS defining manifestations, Pneumocystis carinii pneumonia was the commonest
      (50%), followed by tuberculosis (21%), oro-esophageal candidiasis,
      cryptosporidiosis and toxoplasmosis. Transmission through sex and maternal-foetus
      route could emerge as significant contributors in the spread of AIDS in Bahrain
      unless appropriate preventive steps are taken.

PMID- 10085638
TI  - Value of faecal leucocyte count as an indicator of invasiveness in mucoid
      diarrhoea.
AB  - Importance of faecal leucocyte count as an indicator of invasiveness in mucoid
      diarrhoea was studied. A total of 290 faecal specimen, 170 from mucoid diarrhoea
      and 120 from watery diarrhoea were examined for faecal leucocyte count under high
      power field (hpf) from rural children below four years of age during the period
      from November 1992 to October 1995. Faecal leucocyte count > 10/hpf was noted in
      45.9% of mucoid diarrhoea as against 19.2% of watery diarrhoea (p < 0.0001)
      samples. From faecal samples with > 10 faecal leucocyte count, invasive pathogens
      could be recovered in 19 (24.5%) to none of 23 patients with watery diarrhoea (p
      < 0.006 Fisher exact test). This sample test appears to be of value as an
      indicator of invasiveness in mucoid diarrhoea in the absence of culture facility.

PMID- 10085639
TI  - Current status of filariasis in Chavakad taluk, Trichur district, Kerala.
AB  - A sample survey using parasitological, clinical and entomological indicators was
      carried out in all the 18 administrative units of Chavakad taluk, Trichur
      district, Kerala, India to assess the current filariasis situation. Cluster
      sampling procedure was followed to screen individuals. Both Wuchereria bancrofti
      and Brugia malayi species were found to be prevalent in this taluk. Microfilaria
      (mf) carriers with W. bancrofti were detected in eight areas while B. malayi was
      recorded only from one area. The two species were found to co-exist in another
      area. The highest infection rate registered for W. bancrofti was 1.51 while it
      was 0.3 for B. malayi. Infection due to W. bancrofti constituted 87.88% of the
      total 33 microfilaria cases. Prevalence of B. malayi was very low. Cases with
      clinical manifestation of filariasis were recorded in all the four areas
      surveyed. The present trend in the prevalence of infection (mf) and disease
      showed a decline in both the species when compared to earlier surveys of 1960s.
      At least 11 areas are still endemic for filariasis in this taluk. Although
      prevalence of mf was recorded for the first time in one of the areas viz.,
      Elavalli, the rate was only 0.16%. Entomological surveys revealed the presence of
      14 mosquito species, of which Culex quinquefasciatus contributed 84.85% and
      Mansonia 0.77%. While C. quinquefasciatus was recorded in all the 18 areas,
      Mansonia spp were found only in 8 areas. Only C. quinquefasciatus was found to
      harbour different developmental stages of W. bancrofti, with overall infection
      and infectivity rates of 1.94 and 0.97 respectively. The possible reason for the
      decline in vector density and infection in man are postulated.

PMID- 10085640
TI  - Effectiveness of Bacillus Calamette Guerin (BCG) vaccination against genital
      tuberculosis: a case-control study.
AB  - A hospital-based pair-matched case-control study was performed at Government
      Medical College Hospital, Nagpur, to estimate the effectiveness of Bacillus
      Calmette Guerin (BCG) vaccination against genital tuberculosis. The study
      included 48 cases of genital tuberculosis in the age group of 21-34 years and an
      equal number of controls, matched for age and socioeconomic status. The estimates
      of vaccine effectiveness and prevented fraction were higher for the subjects in
      the age group of 21-30 years and subjects from middle strata of socioeconomic
      class. The overall vaccine effectiveness and prevented fraction was estimated to
      be 75 (38.85-89.79) and 49.99 (17.46-74.55) per cent respectively. Results of
      this study thus indicate that BCG vaccination is effective against genital
      tuberculosis.

PMID- 10085641
TI  - A study on transferable R-plasmids among Shigella species at Lucknow.
AB  - A total of 500 Shigella strains were included in the present study out of which
      233 were isolated at National Shigella Centre of Postgraduate Department of
      Microbiology, K.G. Medical College, Lucknow during last 5 years and 267 strains
      were received from different parts of the country. Predominent serotypes were
      Sheigella flexneri 292 (48.4%) followed by Shigella dysenteriae 153 (30.6%),
      Shigella boydii 32 (6.4%) and Shigella sonnei 23 (4.6%). All the strains were
      sensitive to Nalidix acid, Gentamycin, Kanamycin, Neomycin and Furazolidine.
      Varying degree of resistance was shown to Streptomycin, Chloramphenicol,
      Tetracycline and Ampicillin. R. plasmid extraction was done and transfer was
      studied on E. Coli K-12.

PMID- 10085642
TI  - Role of macrophages in experimental malaria: V--Effect of ethyl palmitate on
      macrophages in Plasmodium berghei infected mice.
AB  - Ethyl palmitate (EP) was used as a macrophage cytotoxin. The response of P.
      berghei after exposing the macrophage to EP was opposite to what was seen with
      other agents like Silica, Antimacrophage serum and Freund's complete adjuvant. EP
      at dose of 5 mg and above decreased the survival period (SP), median survival day
      (MSD) and parasite density 24 hrs. before death (K values). Prepatent period (PP)
      was lower at doses 10 mg and 20 mg per day for 5 days before challenge compared
      to their corresponding controls. EP at a dose of 5 mg and above was found to be
      toxic to host, mice. EP in dosage of 3 mg per mouse administered 48 hrs. before
      challenge resulted in an increase in the mean survival period, survival rate
      (30%) and decrease in the mean parasitaemia per day when compared with the
      corresponding control. The interfering agents affected differently both the host
      and/or parasite. A proper modulation of the macrophage during the course of
      infection may help the host in surviving this lethal infection.

PMID- 10085643
TI  - Note on the fleas of small mammals in Beed district, Maharashtra State, India.

PMID- 10085644
TI  - Knowledge and practice of mothers regarding pulse polio immunization in National
      Capital Territory of Delhi.

PMID- 10085645
TI  - Studies on day-time resting habits of JE vector mosquitoes in upper Assam with a
      note on insecticide susceptibility status.

PMID- 10085646
TI  - Use of Gambusia affinis in different habitats as a mosquito control agent.

PMID- 10085647
TI  - El Nino and its health impacts from WHO fact sheet May, 1998.

PMID- 10085648
TI  - Outrageous.

PMID- 10085649
TI  - Traumatic dental injuries.

PMID- 10085650
TI  - Suspect amalgams.

PMID- 10085651
TI  - Dental care and lung function.

PMID- 10085652
TI  - Whiplash and TMD.

PMID- 10085653
TI  - More about TMD.

PMID- 10085654
TI  - Smoking behavior may be genetic.

PMID- 10085655
TI  - Soybeans may be linked to pain relief.

PMID- 10085656
TI  - Preventing sleep apnea.

PMID- 10085657
TI  - Fluorosis of the primary dentition: what does it mean for permanent teeth?
AB  - BACKGROUND: The prevalence of fluorosis of the permanent teeth has increased
      during the past few decades in the United States and Canada. However, primary
      tooth fluorosis has been largely overlooked, because it is often difficult to
      recognize. This article describes primary-tooth fluorosis, both as characterized
      in the literature and as seen clinically. METHODS: The authors review and
      summarize previous studies of primary-tooth fluorosis and discuss its etiology.
      In addition, the authors describe the condition, based on findings from the
      literature, and their own experiences in characterizing it as part of a
      longitudinal investigation of fluoride exposures, dental fluorosis and dental
      caries. RESULTS: Several studies indicate that primary-tooth fluorosis can be
      prevalent and severe in areas of very high water fluoride concentrations. In
      these areas, primary-tooth fluorosis is likely the result of both pre- and
      postnatal exposures. Studies have documented that primary-tooth fluorosis does
      occur in areas with optimal or suboptimal water fluoride concentrations, and that
      in these settings primary-tooth fluorosis is most likely caused by postnatal
      exposures and is seen most commonly in the primary molars. Primary-tooth
      fluorosis, however, is often more difficult to identify than fluorosis in
      permanent teeth, and clinicians may be unfamiliar with its characteristics and
      may not recognize its somewhat subtle appearance. CONCLUSIONS: Primary-tooth
      fluorosis may be related to occurrence of fluorosis in the permanent dentition,
      so that its recognition by the clinician should raise awareness of possible
      increased risk for the permanent dentition. CLINICAL IMPLICATIONS: The detection
      of primary-tooth fluorosis in a young child should prompt the clinician to
      carefully review the child's past fluoride exposures and current fluoride
      practices, as well as those of any younger siblings.

PMID- 10085658
TI  - Chief complaints of patients seeking treatment for periodontitis.
AB  - BACKGROUND: Hardly any data are available concerning the chief complaints, or
      CCs, of patients with periodontitis. The authors conducted a study to determine
      the most common CCs among a group of subjects with periodontitis. METHODS: The
      authors examined the dental records of 191 patients with periodontitis to
      determine what CCs they orally reported having at an initial examination.
      Patients were referred mainly by other members of the dental health team. Eighty
      percent of the patients were diagnosed with moderate or moderate-to-severe
      periodontitis. The authors recorded the frequency of different CCs to determine
      the most common complaints. RESULTS: The authors recorded 336 CCs from the
      records of 191 subjects with periodontitis. There were 21 different CCs. The most
      common CC reported was, "I was told I have gum disease." The second most common
      CC reported was, "I would like to save my teeth." Neither of these CCs are true
      periodontitis symptoms. Bleeding gums--a true periodontitis symptom--was the
      third most common CC. Only 6.2 percent of the subjects reported having painful
      gingiva, and only 29.3 percent of the subjects reported having dental-emergency
      related CCs. CONCLUSIONS: The authors found that the motivation to seek
      periodontal treatment was most commonly based on information given to the
      subjects by a member of the dental health team, rather than a periodontitis
      symptom. CLINICAL IMPLICATIONS: Renewed efforts and increased responsibility of
      the dental health team members to inform patients about the presence of
      periodontitis are needed, as well as emphasizing to the public the risk of losing
      teeth as a result of periodontitis.

PMID- 10085659
TI  - Improving access for Medicaid-insured children: focus on front-office personnel.
AB  - BACKGROUND: Access to dental services for low-income children is limited. Front
      office personnel play a role regarding dentists' participation in the Medicaid
      program. METHODS: Subjects (N = 24) represented general dental offices in Spokane
      County, Wash., and included participants and nonparticipants in the Access to
      Baby and Child Dentistry, or ABCD, program, a dental society/community program
      aimed at expanding dental services provided to Medicaid-insured children. The
      authors stratified the participants according to the number of claims their
      practices submitted to Medicaid for ABCD children: non-ABCD, low-ABCD and high
      ABCD. Five two-hour focus group sessions were conducted to determine
      participants' beliefs about, attitudes toward and experiences in serving this
      population. RESULTS: The authors' data analysis consisted of a comprehensive
      content review of participants' responses from transcripted audiotapes. They
      synthesized frequently mentioned concepts and ideas into relevant themes. The
      major factors affecting practices' participation in Medicaid were office policy
      on seeing Medicaid-insured patients; staff members' personal connection to
      Medicaid-insured patients; staff members' attitudes about Medicaid-insured
      patients; and staff members' perceptions of Medicaid-insured patients' barriers
      to care. CONCLUSIONS: The data suggest that factors affecting dentists'
      participation in the Medicaid program are more complex than the often-stated
      dissatisfactions with low reimbursement fees and hassles with paperwork. CLINICAL
      IMPLICATIONS: Efforts to increase dentist participation in serving Medicaid
      insured patients will continue to be relatively ineffective until many of the
      concerns raised by this study's subjects are better understood and addressed.

PMID- 10085660
TI  - Basal cell carcinoma: what dentists need to know.
AB  - BACKGROUND: Basal cell carcinoma, or BCC, is a malignant epithelial tumor of the
      skin, commonly seen in the head and neck. Because dentists routinely evaluate the
      head and neck, the authors present three examples of BCC of the face and jaw to
      help clinicians recognize the condition. They also provide a literature review
      regarding BCC's etiology, classification, treatment and prevention. DESCRIPTION
      OF THE DISEASE: Sun exposure plays an important role in the development of BCC.
      The most susceptible people are those with minimal skin pigmentation. BCC is more
      frequently seen in men than in women. The most common form of BCC is the nodular
      type, which, if untreated, eventually ulcerates and may result in extensive local
      tissue destruction. The three cases described in this article highlight the range
      of BCC severity. CLINICAL IMPLICATIONS: Oral health care providers may play an
      important role in the recognition and diagnosis of BCC involving the head and
      neck. Early recognition and diagnosis may lead to management that results in
      improved cure rates, with reduced morbidity and reduced treatment costs.

PMID- 10085661
TI  - Uprighting molars without extrusion.
AB  - BACKGROUND: Orthodontic molar uprighting often results in extrusion of the molar,
      which is not always beneficial. The authors present a strategy for accomplishing
      molar uprighting without extrusion. DESCRIPTION OF THE PROCEDURE: The authors
      review and compare the benefits of molar uprighting with and without extrusion.
      The helical uprighting spring is probably the most popular appliance used for
      molar uprighting. It exerts an extrusive force on the molar during uprighting.
      The authors explain why this appliance produces an extrusive force and present a
      strategy to modify the appliance so that it can be used to upright without
      extrusion. CLINICAL IMPLICATIONS: The information presented in this article
      should help the dental practitioner select a suitable appliance, understand how
      it works and use it appropriately so that molar uprighting can be achieved
      without extrusion of the molar.

PMID- 10085662
TI  - Prevalence of infective endocarditis in patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: Compared with the general population, patients with systemic lupus
      erythematosus, or SLE, have an increased prevalence of functionally impaired
      cardiac valves due to the presence of Libman-Sacks lesions. These lesions may
      place patients with SLE at risk of developing infective endocarditis, or IE.
      METHODS: The authors performed a retrospective chart review to determine the
      association between SLE with valvulopathy and IE. They reviewed the records of
      361 patients from two health care facilities who had the diagnostic code of SLE.
      RESULTS: Of the 275 records that met the 1982 revised American Rheumatism
      Association criteria for SLE, 51 (18.5 percent) were for patients who had a
      clinically detectable heart murmur that resulted in echocardiography being
      performed. Nine (3.3 percent) of the 275 patients had a clinically significant
      valvular abnormality, three (1.1 percent) had a potentially significant valvular
      abnormality, and one (0.4 percent) had a history of IE that was diagnosed two
      years before her diagnosis of SLE was made. CONCLUSIONS: The findings suggest
      that 18.5 percent of this cohort of patients with SLE had a clinically detectable
      heart murmur that would require further investigation to determine its
      significance. Furthermore, between 3.3 and 4.4 percent of the study population
      had cardiac valve abnormalities that potentially required antibiotic prophylaxis
      before certain dental procedures. However, the authors identified no cases that
      demonstrated an association between IE and diagnosed SLE. CLINICAL IMPLICATIONS:
      Dentists should query their patients with SLE about their cardiac status and
      consult with the patient's physician if the cardiac status is unknown. Patients
      with confirmed valvular abnormalities should receive antibiotic prophylaxis for
      designated bacteremia-producing dental procedures.

PMID- 10085663
TI  - Adverse drug interactions in dental practice: interactions associated with
      analgesics, Part III in a series.
AB  - BACKGROUND: Numerous reports of drug interactions exist, yet not all are valid in
      or pertinent to dentistry. This article provides an overview of drug interactions
      with analgesics and identifies those that are clinically relevant. METHODS: The
      author reviewed reports of drug interactions involving nonsteroidal anti
      inflammatory drugs, or NSAIDs (including aspirin), acetaminophen and opioids to
      determine the interactions' validity and clinical relevance. Consistent with the
      practice followed in other articles in this series, the author determined the
      significance of the proposed interaction by gauging its reported severity and the
      quality of the documentation. RESULTS AND CONCLUSIONS: NSAIDs should not be taken
      by patients taking high-dose methotrexate, anticoagulants or alcohol. They should
      be avoided in elderly or renally impaired patients taking digoxin, and avoided
      over the long term in those taking other NSAIDs. It is possible that NSAIDs
      should not be given to patients taking lithium, but future studies should be
      conducted to confirm this. Use of NSAIDs likely is appropriate in the short term
      with patients taking antihypertensives, unless they have severe congestive heart
      disease. Aspirin should not be given to patients taking oral hypoglycemics,
      valproic acid or carbonic anhydrase inhibitors. Acetaminophen may be given in the
      short term to any patient with a healthy liver, but it should not be given to a
      patient who has stopped drinking alcohol after chronic intake. Opioids should not
      be combined with alcohol, and meperidine must be avoided in the patient who has
      taken monoamine oxidase inhibitors in the previous 14 days. CLINICAL
      IMPLICATIONS: Drug interactions with analgesics are often reported, but only a
      small number have clinical relevance in dentistry. Awareness of the significance
      of these interactions will allow dentists to prescribe analgesics optimally and
      minimize the potential for adverse reactions.

PMID- 10085664
TI  - Porcelain-fused-to-metal vs. nonmetal crowns.

PMID- 10085665
TI  - Entering the era of molecular dentistry.

PMID- 10085667
TI  - Ask the experts. How do I select a commercial dental laboratory?

PMID- 10085666
TI  - Does the FTC have authority over nonprofit professional associations? Part I.

PMID- 10085668
TI  - Trend analysis of dental practice rent and mortgage expenses: 1989-1995.
AB  - BACKGROUND: The authors analyzed trends for rent and mortgage, as reported by
      independent active private practitioners, for the period of 1989-1995. Rent and
      mortgage were analyzed overall and by different characteristics. METHODS: In the
      ADA's annual "Survey of Dental Practice," dentists reported gross billings and
      net incomes, as well as itemized practice expenses. The authors tabulated survey
      responses over time to develop trends and compare rent and mortgage expenses for
      each year. If trends over time were not exhibited, the authors combined multiple
      years of data to develop more reliable statistics. RESULTS: Approximately three
      fourths of independent active private practitioners reported rent but no mortgage
      expenses. The percentages of practitioners who reported rent or mortgage was
      stable over time. The percentage reporting rent only as an expense increased with
      the number of dentists in the practice, the age of the reporting dentist and the
      number of office locations. In contrast, the opposite was true for dentists
      reporting mortgage only as an expense. CONCLUSIONS: The authors found that office
      rental is more common than is office ownership and that mortgages as a percentage
      of gross billings and in dollar amounts were similar to rents. They also found
      that because the cost of office space as a percentage of gross billings decreased
      as the number of dentists in the practice increased, limited economies of scale
      may be present in the cost of dental office space. PRACTICE IMPLICATIONS: There
      is not a large financial advantage to ownership, so renting is likely to remain
      an important way to acquire office space. As only limited economies of scale
      exist in office space expenses, many group practices may choose to rent office
      space.

PMID- 10085669
TI  - [Anesthesia and health economics].

PMID- 10085670
TI  - [Anesthesiologic and surgical problems in adenotonsillectomy in pediatric
      patients. Our current trend].
AB  - AIM: To verify, in dissection adenotonsillectomy (AT) performed in Rose position
      under general anaesthesia with oro-tracheal intubation, the following: 1) the
      ability of tramadol to produce an effective intra- and postoperative analgesia
      without any considerable side effects or interferences with the normal post
      surgical course of the operation; 2) the possibility of obtaining, thanks to
      mivacurium, a myoresolution closer both to surgical times of the operation and to
      the necessity of a fast recovering of the pharyngo-laryngeal reflexes.
      EXPERIMENTAL DESIGN: A perspective and retrospective clinical study. SETTING:
      University clinic department (operating room and facility). PATIENTS: 110
      patients submitted to adenotonsillectomy, aged 4-10, belonging to the I-II ASA
      categories and not taking any drug for at least 30 days. INTERVENTIONS:
      Intravenous pre-medication with tramadol 2 mg/kg; myoresolution with mivacurium
      0.2 mg/kg; postoperative analgesia with tramadol 2 mg/kg i.m. one hour after the
      first administration and, with an equivalent oral dose of tramadol, six hours
      later. MEASUREMENTS: During surgery: ECG, HR, Sat HbO2, non-invasive arterial
      blood pressure; after surgery: clinical evaluation of pain, through a three-point
      scale, and of the surgical course. RESULTS: Good analgesical level both during
      and after surgery; myoresolution especially suitable to adenotonsillectomy
      duration and characteristics; no considerable complications. CONCLUSIONS:
      Tramadol intra- and postoperative analgesia and mivacurium myoresolution
      represents, in personal opinion, an efficient approach to dissection
      adenotonsillectomy performed in children under general anaesthesia.

PMID- 10085671
TI  - Oral granisetron as prophylaxis for nausea and vomiting during fluorescein
      angiography. A multicentre, double-blind, randomised, parallel group, placebo
      controlled study.
AB  - BACKGROUND: Prophylaxis with oral Granisetron was assessed in patients undergoing
      fluorescein angiography (FAG) in order to evaluate its efficacy in reducing
      patients' discomfort due to nausea and vomiting (4% > 20%) and to ensure
      completion of the investigation. EXPERIMENTAL PLAN: Multicentre, randomised,
      double-blind, placebo-controlled study, with a follow-up visit performed 24 hrs
      after FAG. ENVIRONMENT: Five Anaesthesia/Resuscitation and Ophthalmology
      operational units participated in the study. PATIENTS: 120 patients (24 from each
      Centre) of both sexes and aged > 18 years, suffering from retinal disorders, were
      enrolled after informed consent. Pregnancy, lactation, anti-neoplastic treatment,
      ASA status IV/V were main exclusion criteria. All recruired patients completed
      the study. INTERVENTIONS: Ophthalmological evaluation was performed 30 days
      before and the same day as FAG. Anaesthesiological assessment on the same day as
      FAG, recording, BP, HR, ASA status, allergic diathesis, allergy to medications
      and contrast media, concomitant treatments. Oral Granisetrom 1 mg or placebo was
      given on an empty stomach 1 hr before the injection of 5 ml 20% fluorescein in 3
      sec. A follow-up examination was done 24 hrs after FAG. SURVEY: In both groups
      nausea, retching and vomiting were seen after fluorescein injection. RESULTS: The
      study demonstrated that Granisetron is more active than placebo in controlling
      nausea (3 cases vs 4), and retching (2 vs 6). It was significantly more effective
      than placebo in the prevention of vomiting (0 vs 3). Efficacy was evaluated with
      chi 2, p < or = 0.05). CONCLUSIONS: The results suggest that Granisetron may be
      indicated as prophylaxis in patients undergoing FAG in order to prevent or
      control emesis, improve patients' comfort and ensure successful outcome of the
      investigation.

PMID- 10085672
TI  - [Catheterization of the subclavian vein through the cannulation of the external
      jugular vein. Our experience].
AB  - The cannulation technique of the subclavian vein by the external jugular vein is
      described. OBJECTIVE: To point out this simple and safe method without
      complications deriving from the direct needle-prick of the subclavian vein.
      METHODS: Experimental plan. The comparative study includes 30 patients in the
      resuscitation department during the second half-year in 1996. Place.
      Resuscitation Department of the University Polyclinic in Palermo. Patients. 30%
      of these patients were male and 70% were female; coagulative serious disorders
      were present in some patients, in others the coagulative picture was unknown.
      Interventions and observations. The modified Seldinger technique has ben used,
      introducing a J wire through the needle cannula put in the external jugular vein,
      taking care not to exceed the length of the latter with the J wire. Less rigid
      and small catheters have been used which can fluctuate in the running blood and
      be carried in the superior vein cava. Once the subclavian vein has been
      cannulated, a Rx graph control of the thorax was made, showing the excellent
      position of the catheter. RESULTS: Only one failure, but this technique has not
      showed complications. CONCLUSIONS: This technique finds applications in all
      situations of extreme emergency, in which on the one hand it needs a central
      blood vessel, on the other there are hemorrhagic problems or there isn't any
      possibility to do a coagulative screening in short time.

PMID- 10085673
TI  - [Atropine poisoning. Importance of the clinical diagnosis].
AB  - A case of suspected high dose atropine poisoning is described. In a veterinarian
      good healthy young man the appearance of light coma with psychomotor agitation
      and the contemporary presence of evident symptoms of muscarinic peripheral block,
      suggesting an anticholinergic syndrome, an atropine-like intoxication in absence
      of toxicological analysis. The safely clinical course of the poisoning during
      observation in intensive care unit permitted the discharge of the patient without
      sequelae and without treatment with physostigmine as antidote.

PMID- 10085674
TI  - [Continuous cervical epidural with ropivacaine in carotid surgery. Description of
      a case].
AB  - In the light of the recent addition of ropivacaine as a local anesthetic to our
      pharmacopeia, its effects at the cervical level are examined. A patient
      undergoing TEAC was given continuous epidural anesthesia with ropivacaine 0.5%
      (total dose: 167.5 mg in three hours) at C6-C7. No supplementary i.v. anesthetic
      was administered intraoperatively. The results obtained were compared with those
      of a similar case as to type of pathology and anesthetic technique, who was
      anesthetised with bupivacaine 0.375% (total dose: 112.5 mg in three hours
      continuous epidural anesthesia) + fentanyl (0.18 mg), supplemented intravenously
      with ketoprophene (200 mg) + fentanyl (0.15 mg) for analgesic reasons. From this
      comparison, ropivacaine 0.5% was found to have greater anesthetic potential than
      bupivacaine 0.375%. However, it did not appear that ropivacaine exerted a
      protective effect on cardiovascular conditions in the course of carotid surgery.
      Further anesthesiologic experiences are needed to define the validity of
      ropivacaine in cervical surgery.

PMID- 10085675
TI  - [Iatrogenic rupture of the left mainstem bronchus in tracheobronchial
      intubation].
AB  - A 74-year-old woman underwent right thoracotomy to remove a lung neoplasm. After
      general anesthesia had been induced, a no. 37 Bronchocath (Mallinkrodt) left
      endobronchial tube (TDL) was inserted. The TDL was initially positioned in the
      right mainstem bronchus and then had to be removed and repositioned in the left
      mainstem bronchus. It was not deemed necessary to use a fibrobronchoscope at this
      stage. During surgery the reduced minute expiratory volume and signs of
      pneumomediastinum made it necessary to perform tracheobronchoscopy. This led to
      the diagnosis of a rectilinear rupture of the left mainstem bronchus starting
      immediately below the carina, at the level of the pars membranacea and extending
      as far as the origin of the superior lobar bronchus. The left TDL was replaced by
      a similar right TDL and emergency left thoracotomy was performed following
      surgical repair of the damage. No problems of note occurred during the
      postoperative period. The patient did not present any of the predisposing risk
      factors for rupture of the tracheo-bronchial tree, except for slight fragility of
      tracheal respiratory mucosa. The anesthetist did not use fibrobronchoscopy or any
      devices to control the pressure level of TDL sleevs during the intubation and
      selection of the bronchus. These aids might have prevented the occurrence of a
      potentially fatal complication.

PMID- 10085676
TI  - [Orthotopic liver transplant. Analysis of costs related to anesthesiologic and
      intensive care phases].
AB  - BACKGROUND: To evaluate anesthesia and Intensive Care Unit (ICU) costs for
      Orthotopic Liver Transplantation (OLT) through a point by point analysis of the
      entire process from anesthesia induction to ICU discharge. DESIGN: Retrospective
      analysis. SETTING: Regional Transplantation Centre participating to the Italian
      National Health Care System. METHODS: Anesthesia and ICU costs for each OLT
      performed during 1997 were estimated through the analysis of costs of the
      following categories: drugs, medical and nurse staff, blood bank, radiology,
      laboratory, haemoderivates. RESULTS: Forty OLTs were performed in 38 recipients
      during the study period. The total charges for the anesthesia and ICU management
      of these patients calculated in US dollars were 583.433,23 (considering the
      exchange rates valid in January 1998). ICU costs resulted approximately 2.5 times
      higher than those for anesthesia. Blood bank and drugs were the categories that
      had the greatest impact on the final expense whereas laboratory had the lowest.
      The charges referred to medical and nurse staff resulted higher in the ICU than
      for anesthesia. CONCLUSIONS: The Italian National Health Care System has to deal
      with limited resources; costs analysis of high-tech procedures as OLT is of basic
      importance to optimise resources allocation and to enforce money-saving actions.

PMID- 10085677
TI  - [From clinical study to daily practice: how much weight does the study design
      carry?].

PMID- 10085679
TI  - [Meeting report. The technologic importance of yeasts].

PMID- 10085678
TI  - [Peridural anesthesia under narcosis in children. The opinion of a group of
      experts on Bromage's article].

PMID- 10085680
TI  - Vulvovaginitis due to Candida glabrata. An emerging problem.
AB  - A review is presented of the emerging problem of resistant and chronic vaginitis
      due to Candida glabrata. Although accurate numbers are lacking, several
      investigators report encountering increased numbers of women with vaginitis due
      to C. glabrata. Possible reasons for this apparent increase are discussed. Risk
      factors and clinical manifestations of symptomatic C. glabrata vaginitis differ
      from those of C. albicans, C. glabrata being less susceptible to fungistatic
      azole agents is more difficult to eradicate. Successful management of chronic C.
      glabrata vaginitis constitutes a major challenge with currently available
      therapeutic agents.

PMID- 10085681
TI  - [Comparison of strain specificity of yeasts from various organs of women with
      vaginal candidiasis].
AB  - Sexual partners harbour often identical yeast strains in the vagina,
      orointestinal tract and sperm in cases of recurrent vulvovaginal candidoses.
      Mycologic cultures from the vagina, mouth and stool of the patient and from the
      mouth and sperm of her partner were cultured on Sabouraud-Glucose-Agar and, if
      positive, specified by Candida ID-Agar (Biomerieux), rice agar and the system
      Walk away (Dade). Equal species were compared by DNR-fingerprinting using PCR.
      The vagina of 22 women was in 21 cases infected by Candida albicans and in one
      case by Candida glabrata. The culture of mouth or stool of 18 women was in 11
      cases identical with those of the vagina. In 13 cases of 18 sexual male partners
      Candida albicans was found being identical with the strain of the female partner
      in 8 cases. 4 of the identical strains were grown from the sperm. Future
      prospective investigations shall prove whether a consequent treatment of both
      partners to eradicate all identical yeasts is able to improve the treatment
      results in such women.

PMID- 10085682
TI  - [Past and present of mycology in German gynecology and obstetrics].
AB  - After the detection of yeasts in 1839, German speaking mycology was first
      performed in obstetrics to find out the source of neonatal thrush. The authors
      are Berg (1846), Mayer (1862), Martin (1856), Winckel (1866), Haussmann (1870),
      Kehrer (1883), Epstein (1924), Ruther, Rieth and Koch (1958), Malicke (1963),
      Blaschke-Hellmessen (1968) and Schnell (1981) and others. In the gynecological
      field yeasts, vaginal mycoses and therapeutic problems had been investigated by
      the gynecologists Doderlein (1892), Spitzbart (1960), Lachenicht and Potel
      (1971), Neumann and Kaben (1971), Muller and Nold (1981) and Mendling (1987,
      1995). Many gynecological papers, however, had also been written by
      dermatologists and microbiologists.

PMID- 10085683
TI  - [Vertical transmission of Candida and its consequences].
AB  - The subpartal transmission of Candida albicans from the vagina of the mother to
      the newborn is an old and often discussed problem. Thereby the decrease of the
      infection rate and the prevention of systemic mycoses due to Candida--especially
      in newborns of risk--are the main objectives. At the end of pregnancy C. albicans
      is found in vaginal secretions in 25-30% of the women. 70-85% of these women
      subpartally contaminate their infants with this yeast. Thus 22-24% of all infants
      acquire C. albicans sub partus. From this situation the following conclusions may
      be drawn: 1. A prepartal prophylaxis for mycoses in pregnant women with vaginal
      Candida colonization is to obtain by an intravaginal treatment with polyene or
      azole antimycotics at the end of pregnancy. Recommendations are offered. 2. A
      prophylaxis for mycoses in newborns which are especially disposed for systemic
      candidosis by several factors of risk is to initiate. The oral application of
      polyene antimycoticas during the considerable endangering by mycoses has been
      proved to be useful. Referring to this recommendations are offered.

PMID- 10085684
TI  - [Is Candida septicemia in premature infants a nosocomial infection?].
AB  - Yeast colonization of the vagina is found in about 30% of all pregnant women.
      Premature infants are severely endangered by generalized fungal infections due to
      their immature immune system. The objective of this study was to elucidate the
      relationship between vaginal yeast colonization of the mothers and Candida
      septicemia in their premature babies. In a prospective study, running from
      12/1994 to 8/1996, 176 mothers, facing probable premature birth, were
      investigated, when hospitalized, for vaginal yeast colonization. 150 premature
      infants (birth weights ranging from 550 to 2390 g) of these mothers were
      culturally examined for yeasts in specimens from the mouth, ear, stool and urine
      immediately after birth as well as once weekly in the following weeks. The
      patients were divided into two groups. In group A, oral prophylaxis with nystatin
      was practiced only in infants with at least one positive yeast culture. In group
      B, all patients received nystatin prophylaxis. Candida septicemia developed one
      or two weeks after birth mainly in infants with birth weights below 1000 g.
      Primary oral prophylaxis with nystatin lowers considerably the risk of developing
      Candida infection.

PMID- 10085685
TI  - [Status of fluconazole in the therapy of endogenous Candida endophthalmitis].
AB  - During the clinical course of invasive candidosis, endogenous Candida
      endophthalmitis (ECE) is associated with a higher mortality. In patients with
      candidemia, an ECE-incidence of 28 to 37% was reported. In i.v.-drug users, the
      incidence of Candida infections was 21%. Besides surgical procedures including
      vitrectomy and enucleation, early initiation of systemic antifungal therapy is
      decisive for the outcome. The clinical use of fluconazole in ECE is documented in
      96 patients and in a minimum of 108 eyes. The mean duration of therapy was 6-8
      weeks (maximum duration: lifelong) with an average dosage of 200-400 mg/d
      (maximum dosage: 800 mg/d and 14 mg/kg BW, resp.). The results reported in the
      literature show a good clinical efficacy of fluconazole in ECE: 90% response rate
      (19/21) in patients with/without concomitant vitrectomy and with/without
      concomitant use of other antifungals, complete disappearance of all eye lesions
      in 94% (15/16) non-neutropenic patients with candidemia and in 86% (6/7) ECE
      patients addicted to heroin. With respect to these favorable results, fluconazole
      plays an important role in the standard therapy of ECE.

PMID- 10085686
TI  - [Fungal arthritis--a rare complication of systemic candidiasis or orthopedic
      intervention. Review of therapeutic experience with fluconazole].
AB  - The higher number of implanted artificial joints, the broader use of aggressive
      treatment regimen, e.g. high-dose chemotherapy and total parenteral nutrition,
      the increasing use of central venous catheters and a broader use of
      immunosuppressive drugs are likely to result in a higher incidence of fungal
      arthritis, especially caused by Candida spp. Therefore, a careful evaluation of
      the available therapeutic options is necessary. The published clinical data on
      the therapeutic use of fluconazole in the treatment of fungal arthritis were
      reviewed. A total of 24 publications report the use of fluconazole in fungal
      arthritis in 32 patients. The mean duration of therapy was 6 months (maximum
      duration: 2 years) with an average dosage of 200-400 mg/d (maximum dosage: 800
      mg/d). Native arthritis was diagnosed in 27 patients, prosthetic arthritis in 5
      patients. In all patients an isolated joint was infected, most frequently the
      knee joint. Fluconazole was effective and safe in acute therapy alone or in
      combination with surgery as well as in long term suppression therapy.

PMID- 10085687
TI  - [Psychosocial risk factors in vulvovaginal mycosis. A multivariate long-term
      study].
AB  - The results of a multivariate logit-analysis of n = 9098 (female) patients of a
      gynecologic practice (from 1991 to 1994) confirm the relevance of psycho-social
      factors like employment, being married, smoking etc. on the incidence of the
      vulvovaginal mycosis. By the statistical results the studied factors can be rank
      ordered from "smoking" as the most relevant to "virginity" as the most irrelevant
      factor. Surprisingly sexual contact and using oral contraception had no
      relevance. A check-list using factor-combinations enables to discriminate 48
      types of female with different risk of incidence. The results of the study are in
      accordance with the following hypothesis: In most cases stress, induced by the
      psycho-social situation of the female and weakening the immune system, is the
      only responsible factor for the incidence of vulvovaginal mycosis.

PMID- 10085688
TI  - [Systemic terbinafine treatment of dermatophytoses in children].
AB  - Terbinafine is the first orally active allylamine. Though it is available since
      several years, experience in children is rather limited. We report about five
      cases of dermatophytoses in children successfully treated with oral terbinafine.
      Five children (age: 10 month to 14 years) with a clinical and mycological
      diagnosis of dermatophytosis were treated with oral terbinafine according to
      their body weight: 250 mg/d (< 40 kg), 125 mg/d (20-40 kg) and 62.5 mg/d (< 20
      kg). The course of treatment was 2 to 4 weeks. In 2/5 patients previous systemic
      treatment with oral griseofulvin failed. Terbinafine therapy resulted in a
      complete clearance of mycotic infections (both clinical and mycological) in 5/5
      children. No unwanted side-effects were observed. During a nine month follow-up
      no relaps occurred. In our five cases tolerability, clinical and mycological
      response of terbinafin therapy were excellent. Its penetration into sebum and
      only slow release from skin glands may explain the efficacy even in short-time
      therapy.

PMID- 10085689
TI  - [Variability of Trichophyton cerrucosum isolates from vaccinated herds with
      cattle ringworm].
AB  - Twenty-seven strains of Trichophyton verrucosum from 14 cattle herds in the
      Federal States of Thuringia and Mecklenburg-Vorpommern were examined by culture
      morphological and molecular biological (PCR fingerprinting, AFLP analysis
      sequencing of ITS region) methods. Six reference strains of the same species,
      among them the so-called album and ochraceum varieties, were also included.
      Despite great variability in terms of culture morphology, which suggested their
      possible classification into 4 different colony types, all T. verrucosum isolates
      were genotypically almost identical. Even the 2 field isolates growing with
      yellow pigment, which could possibly be regarded as belonging to the ochraceum
      variety, could not be differentiated using molecular biological methods. The
      results do not provide indications of a separate taxonomic position of the 3 T.
      verrucosum varieties. Furthermore, there is no evidence confirming the suspected
      infection of cattle herds with ochraceum strains as the cause of the failure of
      immune prophylaxis using various T. verrucosum vaccines. The frequent occurrence
      of animals not responding to vaccination could not be explained either. It should
      be assumed that the main factors responsible for this situation include poor
      handling of the vaccine strains and errors in application, especially the absence
      of continuous and systematic immune prophylaxis in the herds.

PMID- 10085690
TI  - [Fungal nucleic acid detection for invasive aspergillosis].
AB  - A universal PCR-assay for the detection of fungal DNA was compared with
      microscopy and culture for the diagnosis of invasive aspergillosis using 78
      samples from 42 patients. Eighteen patients were suffering from invasive
      aspergillosis, 5 patients were colonized with Aspergillus in the respiratory
      tract, 19 patients did not show any sign of aspergillosis. Samples from 6 of the
      18 patients with invasive aspergillosis were microscopically positive with true
      mycelia, 15 of 18 grew Aspergillus in culture, 16 of 18 were PCR-positive. The
      combination of microscopy and culture led to the diagnosis in 17 of 18 patients,
      the combination of microscopy and PCR in 16 of 18 and the combination of culture
      and PCR in all the 18 patients. For 3 of 18 patients, PCR was the diagnostic key:
      in 2 biopsies the histologically detected fungal elements were identified as
      Aspergillus, in 3 bronchial lavages from 1 patients nothing but PCR was positive
      for Aspergillus. Four out of 5 culture positive patients with Aspergillus
      colonization were also PCR positive; one out of 19 patients without aspergillosis
      was culture positive, 3 out of 19 were falsely PCR positive. Candida colonization
      in the upper respiratory tract or Pneumocystis carinii pneumonia did not lead to
      false positive Aspergillus-PCR results. In conclusion, the evaluated fungal PCR
      assay can supplement conventional methods for the diagnosis of invasive
      aspergillosis.

PMID- 10085691
TI  - [Investigations on the regulation of secreted aspartyl proteases in a model of
      oral candidiasis in vivo].
AB  - By means of RT-PCR and specific primers the expression of SAP1-6 and SAP8 was
      investigated with respect to the time course in an in vitro candidosis model
      based on reconstituted human mucosal epithelium. Corresponding morphological
      alterations of the epithelium were documented by light microscopy. The detection
      of Sap was performed immunoelectron microscopically using a monoclonal antibody.
      In the oral candidosis model SAP1 and SAP3 transcripts were detected 42 h after
      inoculation corresponding to first histopathological changes. Additional SAP6
      expression was observed six hours later concomitantly with germ-tube formation.
      Later on SAP2 and SAP8 transcripts were found after 60 h. On protein level it was
      possible to demonstrate Sap antigens within Candida and markedly deteriorated
      epithelial cells. Initial experiments with proteinase mutants and proteinase
      inhibitors showed reduction of histological damage. In a clinical specimen
      obtained from a twenty nine-year-old female patient suffering from acute oral
      candidosis SAP1, 3 and 6 could be demonstrated corresponding to the findings in
      vitro after 48 h. Investigating a clinical specimen obtained from a lesion of
      chronic oral candidosis in an HIV-infected patient also showed SAP2 expression.
      On the basis of our results a relationship between the expression on of
      particular SAP genes and the turn up of lesions looks as probable as a relevant
      contribution to the in vivo infection.

PMID- 10085692
TI  - [Synthesis of fluorochromes and pigments in Malassezia furfur by using tryptophan
      as the single source of nitrogen].
AB  - A new minimal medium consisting only of L-tryptophan (L-trp) and a lipid source
      induced formation of brown pigmentation only in the species Malassezia furfur.
      Strains of the species M. sympodialis and M. pachydermatis failed to grow on this
      medium. Pigmentogenesis was already induced in M. furfur by 0.01 g% tryptophan,
      the pH optimum was pH = 5. Alternative amino nitrogen sources given concurrently
      with trp suppressed pigmentogenesis. The extract of the culture exhibited
      remarkable fluorescence, and several indole derivatives with a broad spectrum of
      colors were detected by means of mass spectroscopy and NMR. This finding may have
      an impact on the clinical appearance of pityriasis versicolor, a very common skin
      disease caused by lipophilic yeasts of the genus Malassezia. We hypothesize that
      in pityriasis versicolor metabolic adaptation of Malassezia yeasts to altered
      nitrogen conditions on superficial skin might be of pathophysiological
      importance. Tryptophan as inductor of pigmentogenesis probably cumulates during
      excessive sweating, a well known manifestation factor of pityriasis versicolor.

PMID- 10085693
TI  - [Leishmaniasis of the lips mimicking a mycotic infection].
AB  - A 24-year old German man was complaining of painful ulcers with infiltration of
      the lips without alteration of the oral mucosa and swelling of the regional lymph
      nodes. Three months earlier he had visited Israel, Italy, Romania and Bulgaria.
      He was treated with penicillin, doxycyclin, ciprofloxacin, itraconazole and
      prednisolone after detection of Candida spec. and staphylococci in another town
      without any effect. The smear and biopsy were sent to the Robert Koch Institute
      Berlin. Giemsa stain by phase contrast light microscopy with oil immersion showed
      extracellular amastigote leishmaniae with clearly stained kinetoplasts.
      Leishmania major could be detected by PCR investigation. The IgE was elevated,
      other investigations of the blood and from the lips were inconspicuous. The
      ulcers healed promptly under the treatment with Pentostam (antimony derivative)
      0,1 ml/kg body weight i.m. for 12 days and 15% Paromomycin ointment.

PMID- 10085694
TI  - [Incidence of endomycoses in the autopsy material of the Berlin Charite
      Hospital].
AB  - From 1970 to 1993, a total of 93 endomf1p4es confirmed by post-mortem examination
      was diagnosed in the autopsy material of the Berlin Charite, a large hospital
      with an average of 1,500 hospital beds and maximum medical care. These comprised
      51 candidoses (54.8%), 24 aspergilloses (36.6%), five cryptococcoses (5.4%), one
      zygomycosis, 1 trichosporosis and one coccidioidomycoses. This corresponded to
      0.7% of the 13,375 decreased persons autopsied during this period. The frequency
      of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain
      dissection was performed. An adequate clinical putative diagnosis was made in
      only six out of 28 patients (18 adults, 10 children) with histologically
      confirmed cerebral mycosis [11 candidoses (39.3%), 10 aspergilloses (35.7%), five
      cryptococcoses (17.9%), one trichosporosis and one coccidioidomycosis]. About 80%
      of the mycoses of the CNS thus remained undetected while the patients were alive.
      Against the background of the continuing reduction in the frequency of autopsy in
      the Federal Republic of Germany, the observations made in the present paper
      underscore the demand for improved efficiency of mycological in-vivo diagnoses in
      the hospital and laboratory.

PMID- 10085695
TI  - [Pharmacokinetics and dosage of fluconazole in continuous hemofiltration (CAVH,
      CVVH) and hemodialysis (CAVHD, CVVHD)].
AB  - Continuous haemofiltration (CAVH, CVVH) and haemodialysis (CAVHD, CVVHD) are
      increasingly used in patients with acute renal failure (ARF). The elimination
      rates of fluconazole vary considerably among the different procedures. In CVVHD,
      the elimination rate is, depending on the combined dialysate/ultrafiltrate flow
      rate, the most marked compared to CVVH and intermittent dialysis with a
      fluconazole clearance exceeding the values of healthy persons in CVVHD 2 L/h. To
      achieve therapeutic plasma levels during continuous renal replacement therapy,
      the same loading dose as in patients without renal failure should be applied,
      followed by the adjusted maintenance dose for anuric patients multiplied by a
      factor taking the extracorporeal elimination of the absorbed dose into account
      (CAVH, CVVH: x 2.2, ultrafiltrate flow 0.5 L/h; CAVHD, CVVHD: x 3.8, combined
      dialysate/ultrafiltrate flow 1.5 L/h). Despite the broad therapeutic margin of
      fluconazole, drug monitoring is recommended with respect to the very limited
      number of investigations with relatively low dosages up to 200 mg/day and--which
      is of paramount importance--to achieve therapeutic drug levels in vital
      indications.

PMID- 10085696
TI  - [Gerog Fresenius and the species Aspergillus fumigatus].
AB  - The species Aspergillus fumigatus was first extensively described by G.
      Fresenius. J. B. Georg W. Fresenius was born in Frankfurt/Main, Germany, in 1808
      and also died there in 1866. He studied medicine and finished his doctorate
      thesis (MD) in 1829. Afterwards he started his career as a physician and surgeon
      in Frankfurt/Main in the same year. In 1831 Fresenius became a university
      lecturer for botany at the "Senckenbergisches medicinisches Institut"; this
      institute specialized in botany. In this year Fresenius also became the director
      of the botanical gardens of Frankfurt/Main. Apart from his collaboration in the
      institute for agriculture he actively participated in the microscopical
      association of Frankfurt as well as the "Senckenbergische medicinische
      Gesellschaft". Almost over the whole period, Fresenius also worked as a physician
      taking care of miserable people. The outstanding publications of Fresenius are
      "Die Flora von Frankfurt" (Flora of Frankfurt) and "Beitrage zur Mykologie"
      (Contributions to Mycology). The monograph "Beitrage zur Mykologie" was published
      by Fresenius as a dedication for the centennial celebrations of the Senckenberg
      foundation ("Senckenbergische Stiftung"). It contains 132 pages and 13 excellent
      lithographic figures (Camera lucida). The third part of this monograph also
      contains the description of the species A. fumigatus. Fresenius was an engaged
      physician as well as an outstanding researcher and expert in natural sciences who
      described numerous new fungal species some of which are still accepted nowadays
      in accordance with the "International Code of Botanical Nomenclature".

PMID- 10085697
TI  - FASEB Federal Funding Consensus Conference FY 2000. Executive summary.

PMID- 10085698
TI  - [Short-term intensive insulin therapy as a method of overcoming secondary failure
      of sulfonylureas in patients with type 2 diabetes (non-insulin-dependent)].
AB  - The study group comprised 56 patients (25 males and 31 females) with type 2
      diabetes in whom the secondary failure to sulphonylurea derivates (SU) had
      developed. All patients were submitted for 14 days to therapy with 5 injections
      of insulin per day in total dose of insulin permitting to decrease the mean daily
      glycaemia below 8.8 mmol/l (160 mg/dl). After the termination of the intensive
      insulin therapy (IIT) the patients with insulin requirement below 44 U daily were
      alternatively qualified to treatment with SU (glybenclamide) alone or with this
      SU plus biguanide derivate (BG: phenformin), and those who needed more than 44 U
      daily continued conventional therapy with insulin alone or with insulin plus SU
      (glybenclamide). There was a marked reduction of fasting and postprandial blood
      glucose during the IIT and over the subsequent 15 months of the follow-up. The
      mean glycaemia which initially was in fasting state 12.5 +/- 2.4 mmol/l (225 +/-
      43 mg/dl) and 2 hours after breakfast 18.1 +/- 2.8 mmol/l (325 +/- 50 mg/dl)
      decreased significantly and was in four groups between 8.0 +/- 0.3 mmol/l (144 +/
      5 mg/dl) and 10.8 +/- 0.5 mmol/l (194 +/- 9 mg/dl) in fasting state and between
      10.5 +/- 0.3 (189 +/- 5 mg/dl) and 11.2 +/- 0.4 mmol/l (201 +/- 7 mg/dl) after
      breakfast. The least hypoglycaemic effect was found in patients who after IIT
      were treated exclusively with insulin (mean daily dose 53 +/- 2 IU) while the
      decrease of glycaemia was most evident in patients treated with SU given as a
      single drug or in combination with BG or with insulin (mean daily dose 19 +/- 1
      IU). In all studied patients basal and stimulated (1 mg glucagon i.v.) C-peptide
      secretion markedly decreased during IIT, and greatly increased after its
      termination, and this increase persisted over following 15 months of observation,
      correlating with the initial values. CONCLUSIONS: The short-term IIT in patients
      with NIDDM and secondary failure to SU is effective in reducing hyperglycaemia,
      and in most of them makes possible to continue the oral antidiabetic treatment
      with SU. The secretion of endogenous insulin seems to have only limited influence
      on the metabolic control of the patients treated with four different
      pharmacological regiments after IIT.

PMID- 10085699
TI  - [Uremic neuropathy--I. Is uremic neuropathy related to patient age, duration of
      nephropathy and dialysis treatment?].
AB  - The aim of the study was to analyse the relationship between clinical and
      electrophysiological features of uremic neuropathy and age of patients, duration
      of kidney disease, renal failure and dialysis treatment. 51 patients with end
      stage renal failure without diabetes were examined. Apart from a basic
      neurological examination, conduction velocities in the sural and tibial nerves
      were determined, and in order to assess the function of the autonomic nervous
      system, R-R interval variation and sympathetic skin response were tested. In
      majority of patients, symptoms and signs of sensorimotor neuropathy were found,
      and about 50% of them had dysautonomia. A negative correlation between age and R
      R interval variation was observed. No relationship was found between neuropathy
      and the duration of nephropathy, duration of renal nor dialysis treatment.

PMID- 10085700
TI  - [Uremic neuropathy--II. Is pruritus in dialyzed patients related to neuropathy?].
AB  - The problem of pruritus in dialyzed patients remains unsolved. The aim of this
      study was to analyse the relationship between pruritus and clinical symptoms and
      signs, and electrophysiological aspects of peripheral neuropathy, both somatic
      and autonomic. 51 patients with end-stage renal failure undergoing hemodialysis
      were examined. Diabetics were excluded. Apart from taking history and physical
      examination, conduction velocities in peripheral nerves were determined, and R-R
      interval variation (RRIV: assessment of vagal function) and sympathetic skin
      response (SSR) tests were performed. Pruritus was present in about 63% of
      patients. In majority of them, symptoms and sings of neuropathy were also found.
      A significant relationship between pruritus and paresthesia was noted. This
      indicates a possible relationship between pruritus and secondary neuropathy.

PMID- 10085701
TI  - [Levels of leptin in plasma of patients with type 2 diabetes].
AB  - Leptin, the product of ob gene is secreted by adipose tissue. It is believed that
      leptin plays an important role in energy balance. The secretion of leptin by
      adipose tissue is influenced by insulin. The aim of the present study was the
      estimation of plasma leptin concentrations in patients with type 2 diabetes
      mellitus. The study was carried out in 21 diabetic obese patients (BMI > 27.5), 8
      diabetic patients with BMI < 27.5, 24 obese patients with normal glucose
      tolerance (BMI > 27.5) and 10 patients from the control group (BMI < 27.5). The
      mean leptin concentration in obese diabetic patients was 22.5 + 6.5 ng/ml and was
      not significantly different from that in obese patients without diabetes (24.1 +
      10.3 ng/ml) but differed markedly in comparison to the normal weight diabetic
      patients (7.9 + 4.3 ng/ml, p < 0.01). Plasma leptin concentration correlated
      significantly and positively with BMI and fasting insulin in all studied groups.
      There was no significant correlation between leptin and glycated hemoglobin,
      total cholesterol and triglycerides. We conclude that serum leptin concentrations
      in patients with type 2 diabetes depends mainly on the amount of body fat.

PMID- 10085702
TI  - [Use of fourier row as a method for analyzing the course of circadian heart rate
      in patients with left ventricular ejection fraction impairment].
AB  - The circadian heart rate course was assessed in 3 groups of patients with left
      ventricular ejection fraction (LVEF) 10-15%, 20-25% and 30-35%. The study
      comprised 36 persons. In 9 patients heart failure was due to MI and in 17--to
      dilated cardiomyopathy. Those with atrial fibrillation, ventricular tachycardia,
      supraventricular tachycardia, diabetes, valvular heart diseases and with central
      system disorders were excluded from the study. Left ventricular ejection fraction
      was evaluated by echocardiography. Heart rate, calculated as a mean value every 5
      minutes, was taken in patients during 24 hour recordings. For each patient
      separately, mean value of all measurement was calculated. Then a ratio of each
      actual value to the mean value was calculated. This ratio was defined as relative
      heart rate; [formula: see text] Circadian heart rate courses were approximated by
      Fourier row: [formula: see text]. The 24 harmonics were analyzed. Statistically
      significant differences in circadian courses were closed to amplitudes of 1st,
      12th, 13th, 14th, 16th, 18th harmonics. Using test of variance homogeneity it has
      been demonstrated that variability of amplitudes of 12th and 17th harmonics as
      well as phase of 5th harmonic depend on left ventricular ejection fraction.

PMID- 10085703
TI  - [Therapeutic efficacy of low-dose alpha interferon therapy in liver cirrhosis
      associated with HBV].
AB  - The aim of this study was the assessment the efficacy and safety of therapy with
      interferon alpha (Intron A) administered s.c. 3 MU x 3/week for 12 weeks for
      patients with HBV related liver cirrhosis (Child's class A). Fifteen patients
      completed therapy and 12 months follow-up. At the end of follow-up sustained
      response to the therapy, defined by clearance of HBV-DNA, normalization of ALAT
      activity in serum and improvement in the liver histology was achieved in 46.6% of
      treated patients. Moreover, among few patients from group of nonresponders
      (patients without sustained clearance of HBV-DNA) decrease of HBV-DNA level, ALAT
      activity in serum and improvement in the liver histology were observed. Adverse
      effects of IFN alpha therapy were typical, but in any case were no necessity
      terminate the therapy.

PMID- 10085704
TI  - [Bone marrow aplasia and liver damage caused by methimazole].
AB  - We present a case of 52 years old woman with cutaneous lupus erythematosus and
      methimazole induced bone marrow aplasia with agranulocytosis and liver damage.

PMID- 10085705
TI  - [Inhibitors of platelet receptor GP IIb-IIIa--new possibilities of treatment for
      atherosclerosis complications].

PMID- 10085706
TI  - [Hypertension and atherosclerosis].

PMID- 10085707
TI  - [Examining the quality of life in patients with proliferative diseases of the
      hemopoietic system].

PMID- 10085708
TI  - [Metabolic differentiation of insulin resistance in type 2 diabetes mellitus (non
      insulin-dependent)].

PMID- 10085709
TI  - [Natural killer cell count in hemodialysis patients].
AB  - The patients with chronic renal failure present an immunodeficiency state
      manifested by prolonged tolerance to allografts, increased incidence of
      infections and abnormally high incidence of neoplasia. The present study aimed to
      assess the effect of chronic uraemia and haemodialysis treatment on the natural
      killer cells (NK cells) count. Peripheral blood NK cells (CD3-, CD16+), total
      lymphocytes, leukocytes, monocytes and granulocytes of 24 hemodialyzed patients
      with chronic renal failure and 32 healthy subjects were studied using flow
      cytometry. In the investigated group of patients with chronic renal failure
      treated with haemodialysis the count of NK cells (CD3-, CD16+) in the peripheral
      blood was significantly decreased in comparison to healthy subjects (137 +/- 11
      versus 229 +/- 13, p < 0.001) and a significant negative correlation (r = -0.391,
      p < 0.05) was observed between the duration of haemodialysis treatment and the
      count of NK cells (CD3-, CD16+). CONCLUSIONS: 1) Chronic uraemia and
      haemodialysis treatment exerts a negative effect on NK cells (CD3-, CD16+) count
      in the peripheral blood. 2) The count of NK cells (CD3-, CD16+) in the peripheral
      blood in patients with chronic renal failure treated with haemodialysis could be
      a prognostic marker of susceptibility to infections and malignancy.

PMID- 10085710
TI  - [Lack of relationship between angiotensinogen gene m235t polymorphism and gene
      insertion/deletion (I/D-intron 16) and Pst I RFLP (P/M-intron 7) polymorphisms of
      the angiotensin I converting enzyme(ACE) gene and the development of H-gestosis.
      Preliminary results].
AB  - Genetic and familial factors may predispose to H-gestosis. The aim of our study
      was to answer the question if angiotensinogen gene m235t polymorphism, and ACE
      gene I/D and Pst I RFLP polymorphisms may be markers of genetic predisposition to
      the H-gestosis. 246 pregnant women (median age 26 years) were studied (the
      studied group consisted of 116 women with H-gestosis and the control group
      consisted of 130 healthy pregnant women). Genotyping was performed using
      polymerase chain reaction method. Statistical analysis was done by means of
      Statistica for Windows. Genotype distribution was analyzed using chi 2 test. P <
      0.05 was considered as statistically significant. In our study we did not receive
      statistically significant differences in ACE and angiotensinogen genes genotype
      distributions and allele frequencies between the investigated groups. Based on
      results of the study we may suggest that I/D and Pst I RFLP ACE gene polymorphism
      and angiotensinogen gene m235t polymorphism do not play any significant role in
      the pathogenesis of H-gestosis.

PMID- 10085711
TI  - [Analysis of polymorphisms Sma (Hpa II) and Sca I gene precursors of atrial
      natriuretic peptide (ANP) in patients with essential hypertension].
AB  - Both environmental and genetic factors are implicated in the pathogenesis of
      essential hypertension. The defect of the ANP precursor gene leading to the
      decrease of ANP synthesis are a cause of the development of sodium-sensitive
      hypertension in animals. Recent findings in African-Americans who are a model of
      sodium-sensitive population, reveal a strong association between Sma I
      polymorphism at intron 2 (the polymorphic site is identical for Hpa II
      restriction enzyme) or both Sma I and Sca I polymorphism at exon 3 of ANP
      precursor gene and essential hypertension. The aim of our study was to optimize
      the methods for Sma I and Sca I analysis in the ANP precursor gene (PCR followed
      by digestion with restriction enzymes) and to determine the frequencies of Sma I
      or Sca I genotypes and alleles in patients with sodium-sensitive (SS) or sodium
      nonsensitive (SR) hypertension. The Sma I heterozygous mutation (WM genotype)
      were detected in 4 (8.9%) SS patients and in 2 (10%) patients in SR group. The
      frequency of Sca I M allele (allele with mutation) was significantly higher in SS
      group as compared to sodium-nonsensitive hypertensives. Our results suggest that,
      in contrast to Black hypertensives, in Caucasians with essential hypertension the
      Sma I polymorphism is very rare and the Sca I polymorphism of ANP precursor gene
      is associated with sodium-sensitivity of blood pressure.

PMID- 10085712
TI  - [Profile of liver diseases from personal observations].
AB  - In this paper a cohort study from Infectious Diseases Department in Szczecin the
      etiology and dynamics of liver diseases in hospitalized patients from 1994 to
      1996 are presented. The number of patients is increased during this period.
      Chronic liver diseases are common and predominately are cause of by hepatitis B
      virus. Men from urban environmental are most often stricken with sickness.

PMID- 10085713
TI  - [Surgical revascularization of the myocardium in patients with chronic coronary
      disease and depressed left ventricular function: 1-year observation].
AB  - Many reports confirm the importance and benefit of the surgical revascularization
      (CABG) in patients with ischemic heart disease and severely depressed left
      ventricular (LV) systolic function. This mode of treatment is better than medical
      therapy in patients with very low LV ejection fraction (LVEF) and can prolong the
      life. However, the effect of CABG on LV hemodynamics is still unclear. The aim of
      the study was: 1) to assess the effect of CABG on LV hemodynamics in patients
      with low LVEF and 2) to examine the influence of two types of cardioplegia
      crystalloid (CC) and blood (BC) cardioplegia--on LV function during 1 year follow
      up. 122 patients with stable angina pectoris qualified for CABG were included in
      the study. Patients were divided into two groups: group I-47 pts with LVEF < or =
      40% and group II--75 pts with LVEF > 40% and then patients were randomized for
      two types of antegrade-retrograde cardioplegia (CC--subgroups Ia, IIa and BC-
      subgroups Ib, IIb). Before operation and 4 times after CABG (after 2-6 weeks, 3
      months, 6 months and 1 year) echocardiographic examination was performed.
      Diameters of left atrium and ventricle, LVEF and wall motion score index (WMSI)
      were calculated. During 1 year 8 patients died (5 of them during perioperative
      period and 3 patients during follow-up). Patients in group I before operation
      were in higher NYHA and CCS class and had more often myocardial infarction.
      During each of the five echocardiographic examination the values of LVEF and WMSI
      did not differ between subgroups Ia vs Ib and IIa vs IIb. In group I, especially
      in patients with very low LVEF < or = 30%, the values of LVEF and WMSI improved
      significantly (p < 0.001) during 1 year of follow-up. But in group II a transient
      deterioration of LVEF (p < 0.05) 2-6 weeks after CABG was noted. We conclude that
      surgical revascularization in patients with severe depressed hemodynamics
      improves LV systolic function during 1 year follow-up. The use of CC or BC did
      not seem to make any difference to the early and long-term hemodynamic effect of
      the revascularization.

PMID- 10085714
TI  - [Survival of women and men after myocardial infarction does not differ. Results
      of several years' observation].
AB  - The contention that female gender is an independent factor that affects survival
      after acute myocardial infarction (AMI) is still controversial. The aim of this
      retrospective study was to assess whether or not early and late mortality after
      AMI is greater in women than in men. Data of 464 consecutive patients (130 women
      and 334 men) who had a documented acute myocardial infarction in our Department
      of Cardiology between 1990 and 1993 were eligible for the study. We excluded 48
      patients from the study for the following reasons: the location of infarct could
      not be determined in 18 patients: 16 patients refused to take part in the study
      and we were not able to contact 14 patients. The remaining 416 patients were
      analyzed in the study. The mean follow-up period was 36 months (from 1 to 72
      months). Women were significantly older than men (62.1 +/- 11.2 vs 58.1 +/- 11.6;
      p < 0.001), especially those who died in hospital (70.7 +/- 9.3 vs 64.4 +/- 8.7;
      p < 0.01). In hospital died 26 women (20%) and 39 men (11.7%)--p < 0.05. However,
      age-adjusted in-hospital mortality did not differ between women and men (p =
      0.256). We did not find any significant difference in 3-year survival after AMI
      between women and men (22% vs 20.7%; NS). Total mortality was also similar (38%
      vs 30.2%; NS). QMI was diagnosed in 85 women and 234 men (73% vs 78%; NS), NQMI
      in 31 women and 66 men (27% vs 22%; NS). The rate complications of acute phase of
      AMI (acute heart failure and/or rhythm disturbances) was similar in women and
      men. Fibrinolytic treatment was introduced in 27.2% of women and in 26.4% of men.
      Hypercholesterolemia and hypertension were more often associated with female
      gender. In multivariate analysis we found that age, acute heart failure, previous
      MI, hypercholesterolemia and diabetes mellitus were significant factors which
      affects survival after AMI. Of these only age and diabetes mellitus appeared to
      be significant in women.

PMID- 10085715
TI  - [Sporadic case of leptospirosis].
AB  - The flood disaster involves the danger of development of dangerous epidemic and
      episodic events on leptospirotic endemic area in the nearest spring and summer.
      The authors present a case of severe hemolytic leptospirosis as a results of
      gastrointestinal tract infection of 3 strains of leptospira. Polymorphism
      leptospirotic symptoms were discussed. The authors suggest the concept of the
      influence of plasma betaphospho-lipoprotein deficiency on cytoplasmatic
      respiration and substrate phosphorylation of morphologic elements of the blood,
      vessel endothelium and stroma cells.

PMID- 10085716
TI  - [Iatrogenic left main coronary artery stenosis after aortic and mitral valve
      replacement].
AB  - A case of 48-year old patient, who developed anginal symptoms 3 months after
      aortic and mitral valves replacement was presented. The patient underwent
      coronary angiography, which revealed severe left main coronary stenosis.
      Successful surgery was done with grafting of left anterior descending and
      circumflex arteries. Opinions on etiology, diagnosis and management of this rare
      complication are discussed.

PMID- 10085717
TI  - [Mechanisms of action of angiotensin II].

PMID- 10085718
TI  - [Amiodarone and the thyroid gland].

PMID- 10085719
TI  - [Idiopathic thrombocytopenic purpura in adults: diagnostic and therapeutic
      problems].

PMID- 10085720
TI  - [Occurrence of allergy in school-age children and their parents in relation to
      atmospheric air pollution. Prospective study in Cracow].
AB  - The main purpose of the study was to estimate unknown frequency of allergy in
      children and in their parents in Krakow and to check the hypothesis that allergy
      may be related to environmental urban factors. The three-year prospective study
      was carried out in two areas of the city with contrast air pollution levels and
      covered 1129 children. The occurrence of allergy in children was based on
      information from the parents that the disease had been diagnosed by a physician.
      Data on atopy in parents were supported by the information from parents that
      atopy-related diseases had been diagnosed by a physician. The prevalence of
      allergy in boys was much higher than in girls (28.1% vs 17.6%) but the inverse
      was observed in parents--more frequently it occurred in mothers (17.8%) than in
      fathers (12.9%). Among parents the prevalence and incidence of atopy was not
      related to air pollution levels in the place of residence. However, the
      prevalence odds ratio for allergy in children after accounting for potential
      confounders (parental atopy, environmental tobacco smoke, social class and
      household characteristics), was significantly higher among those who lived in
      streets with higher traffic (OR = 1.37, 95% CI: 1.0-1.9) or in vicinity of local
      industrial emission sources (OR = 1.70, 95% CI: 1.2-2.4) but it was not related
      to communal air pollutants (SO2/particulate matter). The similar analysis
      performed for new cases of allergy in children diagnosed over the three year
      period confirmed the conclusions gained from the prevalence data.

PMID- 10085721
TI  - [Calcification of allogenic aortic heart valves].
AB  - The material used for the studies consisted of allogenic aortic valves (AAV)
      collected from 14 individuals. The necessity of AAV replacement arose from
      growing circulation insufficiency and AAV dysfunction. The aim the study was the
      determination of the elemental composition and crystallographic structure of the
      inorganic deposits in AAV. Moreover, the results of the physicochemical
      investigations were correlated with clinical data (age of the patient, time
      between valve replacement surgeries, endomyocarditis, number of infections during
      last 12 months, arterial hypertension and disturbance of the lipid balance) and
      with echocardiographic examinations (cusp mineralization and perforation,
      vegetation, systolic and diastolic dimensions of the left ventricle, maximal and
      average gradient through allograft valve as well as range of the recoil wave to
      left ventricle). It was found that mineralization of the AAV cusps was a time
      dependent process and took place predominantly at the surface of the cusp. The
      elemental composition and crystallographic data revealed that the inorganic
      deposits in AAV were composed of hydroxyapatite crystals. However, the presence
      of other calcium salts was also found. The development of the mineralization
      process in AAV does not correlate with endomyocarditis, arterial hypertension and
      the disturbance of the lipid balance. Probably, endomyocarditis and arterial
      hypertension induce the pathologic alternations of AAV independently from the
      mineralization process. The echocardiographic estimations of the pathomorphologic
      changes of the aortic valve cups are not always consistent with the results of
      the physicochemical studies.

PMID- 10085722
TI  - [Remarks on injuries which were the source of tetanus and were based on
      observations from the Clinic of Infectious Diseases in Cracow].
AB  - From 1992 to 1996, 95 patients with tetanus were treated in the Chair and
      Department of Infectious Diseases in Cracow. Most of them came from rural area,
      and at old age (median 68 years). Small, trivial skin injuries were the most
      often identified portal of entry. Only few patients applied to doctor after
      injury for prophylaxis against tetanus. The authors emphasise that small skin
      injuries, which may be portal of entry for tetanus, should not be left abandoned.

PMID- 10085723
TI  - [Syndrome X--open problem of contemporary medicine].
AB  - Based on the present literature data we have confronted the clinical parameters
      and some pathogenetic mechanisms of the syndrome X. Especially we stressed the
      danger of the accelerated development of the atherosclerotic changes in the
      vessels and the cardiologic complications.

PMID- 10085724
TI  - [Autonomic neuropathy of the cardiovascular system in patients with diabetes. I].
AB  - In the paper, current opinion on diagnostics of cardiovascular autonomic
      neuropathy in diabetic patients was presented.

PMID- 10085725
TI  - [Hormonal islet cell tumors. Proposition of a diagnostic-therapeutic model].
AB  - Islet cell tumors make a serious therapeutic problem due to their specific
      clinical presentation and the necessity of applying a variety of
      multidisciplinary diagnostic and therapeutic methods. The authors present their
      own algorithm for diagnosing and treatment of islet-cell tumors worked out basing
      on many-year experience.

PMID- 10085726
TI  - [Intrahepatic portocaval shunt as a new method for treating and prevention of
      bleeding from esophageal varices in portal hypertension].
AB  - The aim of this study was the presentation of percutaneous transjugular
      intrahepatic porto-systemic shunt (TIPS) and its place among the other methods of
      the treatment of esophageal variceal bleedings. In the period from June 1992 to
      December 1997, 31 cirrhotic patients with portal hypertension and recurrent
      variceal bleedings were submitted for TIPS. This group consisted of 14 female and
      17 male patients, their age ranging from 17 to 68 years (average 52). According
      to Child-Pugh classification 4 patients represented group A, 11--group B and 16-
      group C. Each of these patient was admitted to our Department after recurrent
      bleeding, resistant to typical treatment: terlipressein infusion, balloon
      tamponade and endoscopic sclerotherapy. In 24 patients (78%) TIPS was performed
      successfully. In 7 cases TIPS was performed in candidates for orthotopic liver
      transplantation. CONCLUSIONS: TIPS is quite new, nearly 10 years old method for
      portal decompression. It is an effective and less invasive method than surgical
      procedures in the treatment of portal hypertension, especially in Child-Pugh
      group B and C patients if the sclerotherapy is not effective. It protects
      cirrhotic patients waiting for liver transplantation against the esophageal
      bleedings.

PMID- 10085727
TI  - [Antiproteases in the pathogenesis of neoplastic diseases].
AB  - The imbalance between proteases and their inhibitors has substantial significance
      for the pathogenesis of the neoplastic disease. Proteases have been shown to play
      multiple roles in carcinogenesis and tumor promotion, while antiproteases (PI)
      can be regarded as anticarcinogenic agents. Hypotheses concerning the mechanism
      of PI anticarcinogenic action were presented in this article. The estimation of
      the antiprotease level may be clinically and therapeutically useful in some cases
      of cancer disease.

PMID- 10085728
TI  - [Current diagnostic methods in normotensive hydrocephalus].
AB  - Based on literature of the last 30 years we present the current view concerning
      diagnosis of the communicating hydrocephalus. Till now various methods of the
      assessment of hydrocephalus have been used in order to select patients for shunt
      treatment. No single factor, considered apart from the other diagnostic criteria,
      is sufficient to undertake the decision of shunting. According to current opinion
      the lumbar infusion test is the most valuable in the assessment of hydrocephalus,
      supporting us with the data of pressure-volume relations in patient. Based on our
      own experience the infusion test is not only useful in the preoperative
      investigation, but also for the assessment of proper shunt function.

PMID- 10085729
TI  - [Urolithiasis].
AB  - Epidemiologic investigation did not show any special environmental combination
      causing urinary calculi creation. The disease concerns usually people between 25
      50 year old. Most of the urinary calculi are compound of calcium oxalate and
      phosphate. In contaminated urine more often ammonia-magnesium phosphate. General
      constitutional factors having influence on urinary stones creation are specific
      gravidity, crystallization inhibiting factors concentration, hypercalcuria, urine
      acidity, hyperoxaluria and urinary tract infection. Unilateral, single urine
      stone is usually the effect of the local factors. Bilateral and multiple urinary
      stones are usually the effect of the local factors. Bilateral and multiple
      urinary stones usually are the effect of general constitutional and environmental
      factors. Complaints depend on the stone localisation, its dimensions and period
      of the disease. Nowadays most of the urinary calculi localised in the kidneys and
      ureters are treated with ESWL, PCNL and URS. Staghorn calculi are treated with
      the combination of PCNL and ESWL or operatively. Urinary stones localised in the
      bladder can be the consequence of descending ureteral stones, but usually they
      are created in the bladder as a consequence of the subvesical obstruction. The
      treatment is based on transurethral lithotripsy with simultaneous obstruction
      treatment by electrosurgery of the prostate or bladder neck or visual
      urethrotomy. Large and hard stones can be removed by cysto-lithotomy. Metafilaxis
      is the recurrences prevention, based first of all on diminution of crystalloid
      concentration and their solubility in the urine and providing crystallization
      inhibiting factors. Calculi composed of urine acid can be treated conservatively
      by their dilution.

PMID- 10085730
TI  - [Encephalitis as a severe complication of rubella--case report].
AB  - The case of severe encephalitis in the course of rubeola in young woman was
      presented. The self-limited increased level of aminotransferases and
      hyperglycaemia were reported during the course of disease. Any late complications
      of the encephalitis were observed and the patient was discharge from the hospital
      in good condition.

PMID- 10085731
TI  - [Foreign bodies in the respiratory tract of infants and young children taken from
      personal material].
AB  - The paper presents problems related to the aspiration of foreign bodies to the
      respiratory tract of children aged 0-2 years. The authors analyze the most common
      symptoms corresponding to particular stages of changes in the respiratory tract
      following foreign body aspiration along with their radiological pictures.
      Approximately 65% of aspiration cases in children occur in the period between 6
      months and 3 years of life. The symptoms may suggest a misdiagnosis of chronic
      respiratory tract disease. Detailed analysis of the course of the disease in
      particular children may facilitate proper diagnostic and therapeutic management.

PMID- 10085732
TI  - Demographic, social, and economic effects on Mexican causes of death in 1990.

PMID- 10085733
TI  - Discrimination and Chinese fertility in Canada.
AB  - The study examines Chinese fertility in Canada in the context of minority-status
      and fertility. Chinese-Canadians are compared with British-Canadians, who are
      considered in this analysis as the majority group. The study is unique in three
      ways. First, we argue that discrimination brings a minority group not only
      psychological insecurity but also social-economic insecurity, which can be
      measured by Chinese husbands' economic status relative to the British. Second, we
      analyze the relationship between discrimination against the Chinese at the social
      class level and Chinese fertility behavior at the individual level, which has
      been ignored by most previous studies. Third, we describe "insecurities" effects
      to explain the fertility behavior of the Chinese across social classes, including
      the lower classes to which many researchers believe the minority status
      hypothesis is not applicable. We conclude that discrimination variations over
      social classes combined with normative influence are a major factor in causing
      class fertility differentials between the Chinese and the British in Canada.

PMID- 10085734
TI  - Education as policy: the impact of education on marriage, contraception, and
      fertility in Colombia, Peru, and Bolivia.
AB  - Using data from the World Fertility and Demographic and Health Surveys of
      Colombia, Peru, and Bolivia, we model the effects of education on three
      demographic outcomes: the timing of first sexual union, contraceptive use, and
      fertility. These effects are examined over time and across geographic areas using
      a multivariate framework. We find substantial improvements in female educational
      attainment over the last fifty years and a strong relationship between education
      and the demographic outcomes. Each successive increment in education is
      associated with declines in the marriage rate, increased contraceptive use, and
      lower fertility. Education accounts for some of the changes over time in the
      demographic outcomes, but the pattern varies by outcome, time period, and
      geographic area. In support of the social diffusion hypothesis, our results
      indicate that educational differences in reproductive behavior are reduced as the
      level of development increases and societies pass through their demographic
      transition.

PMID- 10085735
TI  - Relationship of prenatal alcohol use with maternal and prenatal factors in
      American Indian women.
AB  - Demographic factors and patterns of substance use among women who did not consume
      alcohol during pregnancy were compared to women who did consume alcohol during
      pregnancy. One-hundred seventy-seven Northern Plains Indian women who received
      prenatal care at an urban clinic in a rural state were screened for substance use
      as part of the validation study with a self-administered questionnaire. Women who
      drank during pregnancy were more likely to be single and have less education than
      women who did not drink. While most of the women in the study had available
      transportation resources, the women who drank during pregnancy were less likely
      to have transportation than the women who did not drink. Women who drank during
      pregnancy consumed more alcohol more frequently before pregnancy than did women
      who drank before but not during pregnancy. Compared to women who did not drink
      during pregnancy, women who drank during pregnancy were more likely to smoke
      cigarettes and use illicit drugs, to have parents who drank, to feel they drank
      the same or more than other pregnant women, or to have experienced more
      relationship breakups and physical and emotional abuse. Prenatal patients who
      drink alcohol during pregnancy need more intensive counseling regarding their
      multiple risk behaviors.

PMID- 10085736
TI  - Puerperal morbidity: a neglected area of maternal health in Sri Lanka.
AB  - Pregnancy is the period during which a mother prepares herself physically and
      psychologically for the delivery and care of the offspring. However, during this
      period the central concern is the welfare of the baby, but not the mother. When
      the mother and the child subsequently become two separate beings, the mother's
      health care is totally neglected unless she develops obvious symptoms of gross
      physiological and psychological abnormalities. This study, which was carried out
      in three MOH areas of the Kalutara District on maternal morbidity, had two main
      objectives. The first was to determine the prevalence of puerperal morbidity and
      the second was to identify characteristics of those with high levels of
      morbidity. Of the mothers who are registered by the PHM of the study area 600
      were selected for this study. Data were collected using structured interviews
      conducted within the first week after puerperium (43-50 days after delivery). The
      morbidity rate revealed by the study is much higher than expected. Excessive
      bleeding from the vagina was reported by 40 per cent of mothers, while minor
      symptoms like breast engorgement and chills were reported by many mothers. Only
      11 per cent of the mothers in the study did not have any symptoms or signs of ill
      health, and the rest reported one or more illnesses. Primae gravidae and those
      who experienced pregnancy wastage during an early pregnancy had a higher
      morbidity.

PMID- 10085737
TI  - Puberty and the family formation process in Sudan: age-at-menarche differential
      fecundity hypothesis revisited.
AB  - This paper revisits and extends an inquiry on the age-at-menarche differential
      fecundity hypothesis. Earlier studies have interpreted the difference in the
      onset of female pubertal maturation as indicative of biological differences in
      fecundity between early and late menarcheal women. Using the WFS data for Sudan,
      the authors address the entire reproductive life of the women in terms of their
      transition from one parity to the next, as well as the speed with which birth
      intervals are closed, as a way to infer biological fecundity among the women. The
      study concludes that there is little evidence that early menarcheal women are
      more fecund than their late puberty counterparts.

PMID- 10085738
TI  - Assessing the contribution of age-sex differentials in causes of death due to
      infectious and parasitic diseases to the trends in age-sex differentials in life
      expectancy in Mauritius.
AB  - This study applies two methodologies to Mauritian life tables and cause-of-death
      data: (1) the decomposition of sex differentials in life expectancy using
      Arriaga's approach and (2) the estimation of the effect of marginal reduction in
      deaths from infectious and parasitic diseases on life expectancy using Keyfitz's
      methodology on cause-specific entropy and that of Nanjo. The findings in this
      paper support earlier findings about the importance of the period 1969-1976 in
      the mortality transition in Mauritius, a period in which sex differentials in
      life expectancies reached a peak level. The results suggest that the driving
      force behind those sex differentials in life expectancy was the sex differential
      in mortality in infectious and parasitic diseases, first among the young (ages
      below 10 years) and second among the older population (ages above 50 years). If
      the decline in mortality due to infectious and parasitic diseases was
      differentially greater in the older ages compared to the younger ages, that
      difference would have gone a long way toward reducing the magnitude of the
      historic peak sex differential in life expectancy achieved in 1976.

PMID- 10085739
TI  - Maternal smoking in pregnancy and sex differences in perinatal death between boys
      and girls.
AB  - The sex difference in perinatal mortality in developed countries is largely
      unexplained. The current study evaluated the differences in the impact of
      maternal smoking during pregnancy on the risk of perinatal death between males
      and females. The analysis involved 11,469 and 9,404 newborns derived from two
      population-based birth cohorts in Northern Finland, for 1966 and 1985-86,
      respectively. The perinatal mortality rate was 23 per thousand in the 1966 cohort
      and 9 per thousand in the 1985-86 cohort. The rate ratio (RR) for mortality for
      males over females is 1.15 and 1.60 in the two cohorts, respectively. Among
      children whose mothers smoked during pregnancy, the RR was 2.2 (95% CI 1.0, 4.7)
      for the former cohort and 4.8 (95% CI 1.5, 15.2) for the later cohort; and among
      the children whose mothers did not smoke the corresponding RR was 1.2 (95% CI
      0.9, 1.6) and 1.1 (95% CI 0.6, 1.9). Maternal smoking during pregnancy could be
      an important determinant accounting for the excess perinatal death for males over
      females. Our results encourage evaluation of the findings among other
      populations.

PMID- 10085740
TI  - Induced abortion potential among Indian women.
AB  - Information on abortion is limited and inaccurate, especially in the developing
      world, which has led to speculation on the prevalence of abortion in these
      regions. A rise in prevalence of abortion is mostly counted in terms of increase
      in the prevalence of induced abortions which reflects on the reproductive health
      of women. With the growing concern for the reproductive health of women, the
      study of abortion has drawn the attention of researchers world-wide. This paper
      is an attempt to assess the induced abortion potential among Indian women by
      utilizing information on proportion of unwanted and ill-timed pregnancies
      obtained through National Family Health Survey, India. This exercise may
      facilitate a better understanding of the exact prevalence of induced abortion,
      which necessarily should be less than the estimated potential depending on the
      levels of unwanted and ill-timed fertility.

PMID- 10085741
TI  - Mate selection and its impact on female marriage age, pregnancy wastages, and
      first child survival in Tamil Nadu, India.
AB  - Marriage in Indian society is a religious duty. Consanguineous marriage is
      common, where individuals prefer to marry within their clan (a unilateral kin
      group based on either matrilineal or patrilineal descent). Keeping in mind that
      this form of marriage has certain disadvantages for social and biological as well
      as demographic aspects of individuals and families, the present study examines
      the influence of mate selection (i.e., close relatives, distant relatives, not
      related) on female age at marriage, pregnancy wastages, and survival status of
      the first child. The study was designed based on the information collected on a
      sample size of 3,948 married women aged 13-49 in Tamil Nadu, India, by the
      National Family Health Survey (NFHS), 1992. Results suggest that 48 per cent of
      women in Tamil Nadu marry their relatives. This practice of marrying relatives is
      high in rural areas, among Hindus, Scheduled Castes/tribes, and illiterate women
      as compared to urban areas, among non-Hindus, non-SC/ST, and educated women,
      respectively. The bivariate analysis reveals that women marrying their close
      relatives had low age at marriage and experienced a higher per cent of pregnancy
      wastage and child loss (first child) as compared to those women marrying their
      distant relatives or nonrelatives. The result is found to be consistent even
      after controlling for selected background variables through multivariate
      techniques (applied separately for age at marriage, pregnancy wastages, and the
      survival status of first child). Hence, this study suggests that steps should be
      taken to inform people about the problems of marrying close relatives through
      appropriate IEC programs in Tamil Nadu.

PMID- 10085742
TI  - Can the famous really postpone death?
AB  - David P. Phillips has reported evidence that famous people are often able to
      postpone their deaths until after a birthday. A reexamination of Phillips' data
      shows some aspects of his analysis to be questionable, including the lumping
      together of deaths that occur during the birthmonth, which does not distinguish
      deaths that occurred before the birthday from those that occurred afterward. A
      reanalysis of his data shows that there were actually a relatively large number
      of deaths in the month preceding and the months following the birthday. One
      explanation is that the anxiety associated with this milestone and the excesses
      associated with its celebration are sometimes fatal. Another explanation is that
      Phillips' results were a fluke created by a selective use of data.

PMID- 10085743
TI  - [Psychiatric research].

PMID- 10085744
TI  - [From sandbox to brainbox].

PMID- 10085745
TI  - [Transmitter dysfunction in patients with schizophrenia. Significance for
      cognitive functioning and treatment].
AB  - The great diversity of schizophrenic symptoms rules out one simple etiological
      explanation. However,impairment of information processing, including disruption
      of sensorimotor gating, is a consistent finding in schizophrenic patients.
      Dysfunction in sensorimotor gating is believed to be the result of different
      developmentally or environmentally caused disturbances involving the neural
      trajectories involved in information processing. Psychopathology and cognition
      will depend on the primary involvement of distinct parts of these circuits and on
      secondarily derived time-dependent disturbances of transmitter function. This
      review is focused on clinical and preclinical evidence for the impact of
      interactions between glutamatergic, dopaminergic, serotonergic and noradrenergic
      brain systems on cognitive performance. The hypothetical consequences of
      transmitter dysfunction for progressive development of impairment in sensorimotor
      gating are illustrated. Finally, the broad receptor profile of second generation
      antipsychotics is analysed to explain the clinical improvement in neurocognition
      that may occur during treatment with such drugs.

PMID- 10085746
TI  - [Psychiatric service in Denmark].
AB  - The aim of the study was to assess the present psychiatric services in somatic
      departments in Denmark. A questionnaire was sent to all psychiatric departments
      in Denmark. All questionnaires were returned. During 1996 11,602 adult
      psychiatric consultations covering 87% of all beds in general hospitals in
      Denmark were performed. Mean and SD of the consultancy frequency, i.e.
      consultations/somatic bed/year, were 0.62 (0.34). The consultancy frequency was
      significantly higher, when the service included somatic emergency rooms or
      outpatients, or if the consultant performed the consultation together with a team
      member. Furthermore, it was significantly higher, when the consultant attended
      treatment conferences at the somatic departments or yielded supervision. The
      frequency of the psychiatric consultations performed by the staff from the former
      State Mental Hospitals was half of the frequency of the psychiatric departments
      at General Hospitals.

PMID- 10085747
TI  - [The course of affective disorders--a registry study].
AB  - In recent years, studies of the risk of recurrence in affective disorder in
      relation to the number of prior episodes have given contradictory results.
      Survival analysis was used to calculate the rate of recurrence after successive
      episodes in a case register study including all hospital admissions with primary
      affective disorder in Denmark during 1971-1993. Totally, 20,350 first-admission
      patients were discharged with a diagnosis of affective disorder, depressive or
      manic/circular type. The rate of recurrence increased with the number of previous
      episodes in both unipolar and bipolar disorder. Initially, the two types of
      disorders followed markedly different courses, but later in the course of the
      illness the rate of recurrence was the same for the two disorders. The course of
      severe unipolar and bipolar disorder seems to be progressive in nature despite
      the effect of treatment.

PMID- 10085748
TI  - [Is the number of injuries following deliberate violence increasing?].
AB  - The purpose was to estimate the annual incidence of hospital-treated injuries
      related to violence in the city of Odense in the period of 1988 to 1996. The
      overall incidence was estimated to 0.57 (1996) per 100 persons per year, with the
      highest incidence among men between 15 to 25 years. The lifetime cumulative
      incidence proportion was estimated to 45% for men and 21% for women. During the
      period 1988-1996 the overall annual incidence showed a slight decrease.

PMID- 10085749
TI  - [Deaths among inmates in the institutions of the Prison Service. Deaths in
      prisons, county jails etc].
AB  - The purpose of the study is to investigate the number and the character of deaths
      during stays in prisons, county goals etc. During the study period from 1992-1996
      with approx. 38,000 imprisonments per year there were 74 deaths, 71 males and
      three females. The average age was 32.4 years. Approximately 16% had foreign
      citizenship. Twenty had leave, legal or illegal when death occurred. There were
      34 suicides, 22 accidents, 3 homicides and 15 cases of natural death. Several
      deaths took place relatively shortly after the arrival at the institution, one
      third within a week. The most frequently used suicidal method was hanging. The
      accidents were dominated by poisoning deaths, often with morphines, possibly in
      combination with alcohol or other drugs. Two of the three homicides took place
      during leave. Among natural deaths, heart death was the most frequent cause of
      death with six of 10 unexpected deaths. Among expected deaths in prison there
      were three AIDS patients. Fourteen of the fifteen natural deaths had a
      substantial alcohol consumption and/or drug abuse. There ought to be a central
      registration of deaths in prisons and similar institutions. The autopsy frequency
      should be high, and forensic chemical investigation should be used more often.
      Drug dependent inmates should be informed about reduced tolerance to drugs in
      relation to release and leave.

PMID- 10085750
TI  - [Puerperal psychoses. Clinical diagnoses and relative risk of admission after
      parturition].
AB  - Previous studies have suggested that the risk of psychosis, especially affective
      psychosis, is greatly increased during the first 30 days following delivery. The
      aim of our study was to replicate these findings. Linking The Danish Medical
      Birth Register and The Danish Psychiatric Central Register from January Ist 1973
      to December 31st 1993 has revealed 1253 admissions diagnosed as psychosis within
      91 days after delivery. The admission rate following delivery was compared to the
      admission rate among non-puerperal women in the general, Danish female
      population. The relative risk of all admissions was only slightly increased, RR =
      1.09 (CI, 1.03-1.16). The admission rate concerning first admissions was greatly
      increased, RR = 3.21 (CI, 2.96-3.49) whereas the admission rate concerning
      readmissions was reduced, RR = 0.66 (CI, 0.61-0.72. In conclusion, childbirth is
      a strong risk factor for first admission with psychosis, but the risk is less
      increased than previously assumed.

PMID- 10085751
TI  - [Neuropsychiatric disorders in insulinoma].
AB  - The case of a young female presenting severe mental problems and episodic
      neurological symptoms is described. Obsessive-compulsive disorder was diagnosed
      upon psychiatric treatment for eight months. No neurological condition was found.
      Hypoglycaemia was observed during an episode of long-lasting somnolescence and
      the patient referred for endocrinological examination. Reactive hypoglycaemia was
      ruled out in an oral glucose tolerance test. A test of prolonged starvation
      revealed hypoglycaemia associated with neuropsychiatric symptoms. Glucose
      abolished this condition, suggesting an insulinoma as the basis of the
      spontaneous hypoglycaemia. Subsequently, two insulinomas were resected from the
      tail of the pancreas. The patient has recovered completely after her surgery,
      with no signs of mental or neurological disease and blood glucose within normal
      limits. As insulinoma is often associated to the MEN1-syndrome, the patient and
      her relatives are now being investigated for this condition.

PMID- 10085752
TI  - [Long-lasting neuropsychiatric side-effects following mefloquine prophylaxis. A
      case after six weeks of initiating and lasting six months].
AB  - Neuropsychiatric side-effects from mefloquine are well known. When used for
      prophylaxis, the side-effects have been claimed to be relatively rare, mild and
      transient, most often arising within two to three weeks, and in patients with a
      previous history of neuropsychiatric disorders. We here describe a case of severe
      neuropsychiatric side-effects arising six weeks after initiating mefloquine
      prophylaxis, requiring repeated hospitalization, and not resolving completely
      after six months, in a previously healthy 30 year-old female.

PMID- 10085753
TI  - [Neuroleptic malignant syndrome after treatment with olanzapine].
AB  - A case of neuroleptic malignant syndrome (NMS) in a 23 year old male patient is
      reported. The symptoms were hyperthermia, muscle rigidity, change in mental
      status, sinus tachycardia, creatinine phosphokinase elevation and myoglobinuria.
      The patient suffered from severe muscle pain and compromised respiratory
      function. Treatment was cessation of neuroleptic medication and institution of
      intensive medical care focusing on symptomatic treatment. One week after
      admission clinical status and laboratory findings were normalized and the patient
      was readmitted to a psychiatric hospital. The neuroleptic medication of the
      reported patient had been olanzapine during seven months at a dose of 25 mg
      daily. The day before onset of NMS the pharmacological treatment was supplemented
      by 100 mg of clozapine. The cause of onset of NMS in this case is discussed.
      Clozapine, an atypical neuroleptic, is known to have reduced potential to cause
      NMS and in such cases without extrapyramidal symptoms. Olanzapine, however, has
      not yet been reported to cause NMS. Alternatively the cause of onset of NMS in
      this patient could be explained by the combination treatment and possible
      synergistic effect of the two antipsychotic drugs. Further research in this field
      is needed.

PMID- 10085754
TI  - [Breast cancer: improved survival in low-risk patients].

PMID- 10085755
TI  - [Continuous use of mercury manometers].

PMID- 10085756
TI  - [Distribution safety of common pharmaceuticals. A question to
      Laegemiddelstyrelsen and to Nycomed].

PMID- 10085757
TI  - [International research: a comment].

PMID- 10085758
TI  - [Insufficient guidelines on a public disease].

PMID- 10085759
TI  - [Treatment of amyotrophic lateral sclerosis (ALS)].

PMID- 10085760
TI  - ["Heart magnyl"].

PMID- 10085761
TI  - [Reevaluation of a discarded hypothesis of the 40's?].

PMID- 10085762
TI  - Culling policies in dairy herds. A review.
AB  - The culling decision is one of the most complex decisions in farm animal
      management. This article reviews concepts of culling, risk factors for cows to be
      culled, different culling policies and the present knowledge on how to develop an
      optimal culling policy. It is pointed out that there are major interactions
      between other management complexes and culling that influence the result of field
      research concerning risk factors for culling. The estimated importance of risk
      factors for culling varies widely in literature. Culling decisions are part of
      the overall herd management. They cannot be analysed independently. Future
      research should analyse the interactions between management practices, cow
      health, economy, and culling in more detail.

PMID- 10085763
TI  - Intrauterine infection with bovine virus diarrhoea virus on alpine communal
      pastures in Switzerland.
AB  - This study involved 13 calves, one to 50 days of age, born to first calf heifers
      that had been pastured on one of seven alpine communal pastures in the canton of
      St. Gallen during the summer of 1995. Of a total of 993 cattle pastured, 61 were
      pregnant heifers that were negative for bovine virus diarrhoea (BVD) antigen and
      for BVD antibodies at the start of pasturing. Seroconversion occurred in 26 of
      these pregnant heifers during the pasture period. Blood samples and skin biopsy
      specimens of calves born to 13 of these were examined for BVD antigen by antigen
      ELISA and by an immunohistochemical technique, respectively. Blood samples were
      positive for BVD antigen in four calves, questionable in one calf, negative in
      seven and missing in one prematurely born calf. The four calves that were
      positive for BVD antigen in the blood were also positive in skin biopsies. Of the
      seven calves with a negative or missing blood test, six had positive and two had
      negative skin samples. Based on the combined results of blood and skin testing,
      11 of 13 calves were positive for BVD antigen. Of the 11 infected calves, six
      were normal at birth, four were smaller than normal and one was premature and
      weak and was euthanized on humane grounds. Of the four small calves, two
      developed diarrhoea and died within the first month of life. The two calves that
      were negative for BVD antigen were clinically normal. The results of this study
      not only demonstrate the occurrence of in-utero infection with BVD virus, but
      also stress the importance of alpine communal pasturing in the spread of BVD
      virus. Because the prevention of infection with BVD virus on communal pastures
      does not seem feasible, it is recommended that all calves born to cows from such
      pastures be tested for BVD antigen.

PMID- 10085764
TI  - Characterization of a canine CD44 specific monoclonal antibody.
AB  - Monoclonal antibodies (mAbs) were generated against a CD44 mRNA expressing (RT
      PCR) macrophage/monocyte cell line (DH82) from a dog with malignant
      histiocytosis. The mAbs, that reacted with DH82 cells by FACS analysis were
      tested on formalin-fixed, paraffin-embedded tissues. Exclusively the incubation
      of DH82 cell pellets with mAbs from clone 2D10 resulted in a cell membrane
      associated immunoreaction. Immunoelectron microscopy specified, that the antibody
      bound exclusively to the cell membrane and processes of DH82 cells. The mAb was
      tested on a variety of normal canine tissues, including lymphoid, urinary,
      alimentary, respiratory, and endocrine organs, nervous tissues, liver, pancreas,
      skin, and muscles. Furthermore, tumour and inflamed tissues were tested for
      immunoreaction with the mAb. Immunohistologically, the 2D10 mAb reacted with
      macrophages/monocytes, subsets of lymphocytes, epithelial cells, and central
      nervous system white matter. FACS analysis of canine peripheral blood leukocytes
      showed, that a high proportion of lymphocytes and granulocytes were positive with
      this mAb. Western blot analysis revealed, that the 2D10 mAb bound to a protein
      with a molecular weight of about 85 kDa. The results of FACS and Western blot
      analyses, RT-PCR, immunohistology and immunoelectron microscopy strongly suggest
      that the antigen detected by the 2D10 mAb is most likely the canine equivalent of
      human CD44, a cell bound hyaluronan binding proteoglycan.

PMID- 10085765
TI  - Pregnancy rate after ultrasound-guided follicle aspiration in nonlactating cows
      from different breeds.
AB  - Thirty-six cows (21 Simmental, 5 Holstein-Frisian, 5 Brown Swiss and 5 Charolais)
      with high genetic superiority were punctured by ultrasound-guided follicle
      aspiration within the last 18 months for 503 times under equal conditions.
      Follicle aspiration was done twice per week. Most of the donor cows suffered from
      several disturbances of fertility. On average, 5 oocytes per session were
      collected. After in vitro maturation (IVM), fertilisation (IVF) and culture
      (IVC), 0.8 embryos per puncture session were transferred. After evaluation of the
      embryos by morphological criteria, these embryos were transferred to heifers that
      were oestrus synchronised (2.0 ml Estrumate i.m.) seven days after onset of
      oestrus. On day 21 after onset of oestrus the progesterone level in plasma was
      determined by radioimmunoassay. The pregnancy control was performed by ultrasound
      on day 35. After transfer of 397 embryos (to synchronised heifers), 125
      pregnancies were established. Comparison of the different breeds and donor cows
      revealed significant differences in the number of oocytes recovered, embryos
      produced and pregnancies established. Transfer of embryos with insufficient
      morphological quality resulted in increased rates of embryonic loss between day
      21 and day 35.

PMID- 10085766
TI  - Studies on equine lipid metabolism. 2. Lipolytic activities of plasma and tissue
      lipases in large horses and ponies.
AB  - The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly
      investigated at this point in time. It is still unclear why ponies in contrast to
      horses may become hyperlipaemic when coming negative energy balance. In this
      study, the activities of the triglyceride-cleaving key enzymes of ponies are
      large bred horses were investigated in order to obtain insight into the aetiology
      of the syndrome. The objective of the study was to measure the activities of
      hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride
      lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine
      (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 +/- 2.09
      nmol FFA.10(5) cells-1.min-1). This was not observed in horses. Lipolysis was
      significantly higher in fat cells of ponies than in horses when adenosine
      deaminase (ADA) and NE were added (12.71 +/- 3.12 vs. 1.96 +/- 1.22 nmol
      FFA.10(5) cells-1.min-1). Relative inhibition of lipolysis by the action of
      insulin was comparable in adipocytes of horses and ponies. However, absolute FFA
      release in pony fat cells was as high as the maximal NE and ADA stimulated
      lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and
      horses did not differ between the sub-species. This finding was supported by the
      results obtained from measurement of LPL activity in adipose and muscle tissue
      showing only a tendency of increased activities in pony explants when compared to
      horse tissue incubations. This study further supports the hypothesis that
      differences in regulation of TG release from fat stores rather than clearance of
      TG from plasma is causative for the development of hyperlipaemia in ponies.
      Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty
      acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL,
      lipoprotein lipase; NE, norepinephrine; SDS, sodium dodecyl sulfate; TG,
      triglyceride; VLDL, very low density lipoprotein.

PMID- 10085767
TI  - Comparative pharmacokinetics of diminazene in lactating goats and sheep.
AB  - The pharmacokinetic aspects of diminazene aceturate were studied in lactating
      goats and sheep after single intravenous and intramuscular administrations of 3.5
      mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed
      phase high-performance liquid chromatography (HPLC) after ion-pair extraction.
      Following intravenous injection, the disposition of diminazene in goats and sheep
      conformed to a two-compartment model with rapid distribution and slower
      elimination phases. Values of (t1/2 beta) were obtained indicating a slower final
      disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h).
      Diminazene concentrations were maintained for more than 4 days in the plasma of
      goats and sheep. In both species of animals, diminazene was rapidly absorbed
      following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma
      concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at
      (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half
      life (t1/2el) of diminazene after intramuscular administration was shorter in
      goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of
      diminazene after intramuscular administration were 94.94% and 82.64% in goats and
      sheep, respectively. Diminazene could be detected in milk of goats and sheep
      within 10 min post-injection. Milk concentrations of the drug were lower in goats
      than in sheep and were detected for 5 and 6 days following both routes of
      administration, respectively.

PMID- 10085768
TI  - Elimination half-lives of sulphadimethoxine and its N4-acetyl metabolite in
      tissues of laying hens.
AB  - The depletion rates of sulphadimethoxine (SDM) and its metabolite N4
      acetylsulphadimethoxine (N4-AcSDM) were estimated in blood and various tissues of
      laying hens. The tissue contents (ppm) of SDM and N4-AcSDM after the withdrawal
      of SDM, which was fed to hens at 400 ppm diet for 5 successive days, were
      determined by HPLC. The elimination half-life (t1/2) of N4-AcSDM in the liver,
      ovary and muscle was estimated to be 4.3 h with a 95% confidence interval from
      3.6 to 5.3 h. No significant difference between t1/2 of N4-AcSDM in the tissues
      and that of SDM (4.4 h) in the blood, kidney, muscle, ovary and adipose tissue
      was observed. On the other hand, the t1/2 of N4-AcSDM in the kidney (8.1 h) was
      significantly longer than that in the above 3 tissues.

PMID- 10085769
TI  - Simplified preparation of a specific S. enteritidis antigen for ELISA and other
      immunological techniques.
AB  - This study was conducted to prepare a specific S. enteritidis antigen (FG
      Antigen) for the serological detection of S. enteritidis infections in chicken
      flocks. This antigen (FG-Antigen) consistent mainly of the flagellar fraction H:g
      and partly of the fimbrial fraction SEF14 from a S. enteritidis-phage type 4
      strain. The initial steps followed in the preparation of this antigen were
      conducted based on a previously described procedure, which involved the
      application of heat at 60 degrees C. The purification process (filtration and
      concentration) enabled the exclusion of the cross-reaction causing LPS antigens
      from the preparation and allowed the retention of S. enteritidis-specific
      antigens composed of fimbria and H:g fractions. As a result, no cross-reaction
      with S. typhimurium nor with S. gallinarum was exhibited by the prepared FG
      antigen. To characterize and determine its specificity, the following laboratory
      tests were conducted: indirect ELISA, immunoblotting and a SEF14 agglutination
      test. In these examinations, rabbit and chicken reference sera as well as chicken
      field sera and absorbed hyperimmune sera against H:g-carrying serovars were used.

PMID- 10085770
TI  - Detection of antibodies to S. enteritidis in broilers by means of indirect ELISA
      and chemiluminescent immunoassay (CLIA).
AB  - This study was conducted to develop a serological detection system for the
      monitoring of broiler flocks for Salmonella enteritidis infections. A specific S.
      enteritidis antigen (FG-Antigen) was used to compare the sensitivity and the
      specificity of the chemiluminescent immunoassay (CLIA) with those of the indirect
      ELISA. This comparison was performed using a total of 578 sera, which, depending
      on the microbiological and vaccination history, were categorized into groups.
      Most of the serum samples which were classified as positive showed higher titers
      in CLIA than in ELISA. Using the prevalence of positive reactors, significant
      differences between Groups were additionally demonstrated. The absorbance values
      of the passively immunized group showed the highest and those of the Salmonella
      negative group the lowest correlation-coefficient. Using the mean net absorbance
      of the prevalence group, the ELISA system exhibited a sensitivity of 100% and a
      specificity of 96.2%, while CLIA had a sensitivity and a specificity of 85.7% and
      96.2%, respectively. ELISA and CLIA can be used in the examination of non
      vaccinated flocks for S. enteritidis-infections as alternative to the
      bacteriological culture method. CLIA is distinguished for its fast and convenient
      procedure as well as for its wider measurement spectrum, while the indirect ELISA
      is almost as efficient as CLIA and requires less investment.

PMID- 10085771
TI  - Efficacy of sustained release needle-less ceftiofur sodium implants in treating
      calves with bovine respiratory disease.
AB  - Three experiments were conducted to determine preliminary efficacy of sustained
      release needle-less implants in effecting cure in calves with bovine respiratory
      disease. One hundred and twenty beef calves with a rectal temperature > or = 40
      degrees C and shallow or labored respiration and coughing were used in these
      experiments. Four groups (1-ceftiofur sodium injections [days 1, 2, and 3], 2
      ceftiofur sodium needle-less implants [days 1, 2, and 3], 3-ceftiofur sodium
      needle-less implants [days 1 and 3], and 4-ceftiofur sodium needle-less implants
      [day 1] were included. All treatments contained 250 mg of ceftiofur sodium and
      were administered intramuscularly in the neck after diagnosis of bovine
      respiratory disease. Experiment 1 included 20 calves (group 1-10 calves and group
      3-10 calves; 213 to 255 kg) and calves were monitored for clinical efficacy.
      Experiment 2 included five calves per group (all four groups; 164 to 192 kg) and
      calves were bled frequently after treatment for desfuroylceftiofur (the primary
      ceftiofur metabolite) concentrations. Experiment 3 included 20 calves per group
      (all four groups; 160 to 205 kg) and calves were monitored for clinical efficacy.
      Blood desfuroylceftiofur concentrations remained above the minimum inhibitory
      concentration for Pasteurella haemolytica, Pasteurella multocida, and Haemophilus
      somnus for 24 hours after injection and 72 hours after implantation (P < 0.05).
      Mortalities and the number of calves with a positive response and relapse
      response were similar (P < 0.25) among the four groups. In summary, the
      administration of one-250 mg ceftiofur sodium needle-less sustained release
      implant was as efficacious in treating bovine respiratory disease as three daily
      250 mg injections of ceftiofur sodium.

PMID- 10085772
TI  - Measurement of the residual contamination of post-weaning facilities for pigs and
      related risk factors.
AB  - A survey was designed in France to assess residual contamination in post-weaning
      rooms within the 2 h prior to restocking when all the pigs of the previous batch
      had been removed (all in-all out) and after application of the 'in use' cleaning
      procedures. The protocol was based on the results of a pilot study and was
      considered 'a good compromise'. Special agar plates (Rodac plates) with a
      prominent agar medium surface were prepared and used to collect the bacteria.
      They were applied by impression onto the floors and the partitions between the
      pens. In all, 24 plates were applied per room. The culture medium was VRBG which
      mainly permits the growth of enterobacteria. The plates were incubated for 24 h
      (37 degrees C) and the Colony-Forming Units (CFU) counted. After sampling,
      measurements were made and information collected from the farmer to obtain
      potential explanations for the resulting microbiological data. The same scientist
      sampled 129 post-weaning rooms with slatted floors. Of the 3045 plates, 18.4%
      were negative and 12.8% were heavily colonized (> 300 CFU). A score combining six
      criteria based on the counts was produced, and indicated a wide spread of the
      rooms. The profile of circumstances associated with the different levels of the
      score was extracted. The following points should be respected to achieve low
      residual contamination: removal of the slurry from the pit below the slatted
      floor; damping to be started soon after pig removal; prolonged damping; thorough
      washing; disinfecting soon after washing; and attention to the recommended dosage
      of disinfectant. Smooth surfaces were found to be less contaminated than rough
      ones. It is concluded that cleaning and disinfecting operations must not be
      considered as minor tasks and should clearly be integrated into the process of
      pig production.

PMID- 10085773
TI  - Protective activity of the purified protein antigen of Erysipelothrix
      rhusiopathiae in pigs.
AB  - We purified the protein antigen (P64), which contains 66 and 64 kDa proteins,
      from the alkaline extract (AE) of whole cells of Erysipelothrix rhusiopathiae
      strain Agata (serovar 5) to determine the protective activity of the antigen
      against E. rhusiopathiae infection in pigs. The serum titre of antibody against
      P64 rapidly increased in pigs immunized with 500 and 100 micrograms of P64 and
      reached maximum values at 3 weeks after the first immunization (1 week after the
      second immunization). However, the serum antibody titres were not increased in
      pigs immunized with 20 micrograms of P64 and in nonimmunized pigs. In the pigs
      immunized with live cell vaccine (acriflavin-fast attenuated strain Koganei 65
      0.15), the serum titres of antibody against P64 also increased at 1-2 weeks after
      immunization. In a pig challenge test performed on immunized and nonimmunized
      pigs, all nonimmunized pigs showed typical clinical signs of swine erysipelas
      (fever, erysipeloid, arthritis), while all pigs immunized with 500 and 100
      micrograms of P64 and live cell vaccine showed no clinical signs of this disease.
      In Western blot analysis, sera from pigs immunized with P64 and live cell vaccine
      strongly reacted with the 64 kDa protein. In contrast, the serum from
      nonimmunized pigs did not react with any proteins. From these results, it was
      suggested that a specific antibody against the 64 kDa protein could be increased
      in pigs immunized with P64 or live cell vaccine and that this anti-P64 antibody
      has a strong protective effect against E. rhusiopathiae infection in pigs.

PMID- 10085774
TI  - Replication of reptilian paramyxovirus in avian host systems.
AB  - The reptilian paramyxovirus GOV replicated in chicken embryo fibroblasts, in
      embryonated chicken eggs and in explanted chorio-allantoic membrane with titres
      of up to 10(8.2) TCID50/ml at 28 degrees C. The virus did not multiply above 30
      degrees C. GOV re-isolated from the avian host systems was identified by
      immunofluorescence and by immunogold-electron microscopy.

PMID- 10085775
TI  - Incidence of classical swine fever (CSF) in wild boar in a densely populated area
      indicating CSF virus persistence as a mechanism for virus perpetuation.
AB  - A virological survey was carried out to establish the distribution of classical
      swine fever (CSF) virus among wild boar in the Federal State of Brandenburg,
      Germany. Organ materials and blood samples were collected from 11,670 wild boar
      shot or found dead during the period March 1995 to December 1997. In total 211
      (1.8%) wild boar were positive for CSF virus or antigen. The incidence of CSF
      positive animals decreased continuously from 4.6% at the beginning of the
      epidemic in 1995 to 0.7% in 1997. The highest incidence of positive animals (22%)
      was found in wild-boar piglets younger than 3 months of age in 1995. The findings
      were indicative for the decisive role which young wild boar play in the
      epidemiology of CSF. Following intrauterine transfer some of the wild-boar
      piglets were probably persistently infected with CSF virus as experienced
      experimentally. Such piglets can be held responsible for CSF virus perpetuation
      within the wild-boar population. No CSF virus was isolated from adult wild boar
      weighing more than 75 kg. During 3 years of monitoring a sufficient number of
      susceptible wild boar, in particular young animals, was available to maintain the
      infection chain in that area. It was concluded that persistently infected piglets
      and the high population density of wild boar in the Brandenburg region offered
      optimal conditions for the establishment of an CSF epidemic.

PMID- 10085777
TI  - Dr Yellapragada SubbaRow (1895-1948): the man and the method.

PMID- 10085778
TI  - Gastrin producing G-cells after chronic ethanol and low protein nutrition.
AB  - Male Wistar rats, (2 months old), randomly divided according to the diet offered
      to four groups (C-control; A- alcoholized, PD-protein-deprived, A-PD- alcoholized
      protein-deprived). In group A and A-PD rats, the number of gastrin producing G
      cells was significantly lower. The volume density of G-cells was significantly
      decreased in alcoholic rats. Fasting serum gastrin level (FSGL) significantly
      raised due to combined effect of alcohol consumption and protein malnutrition. In
      group A rats, the profile area of G-cells and their nuclei increased. In PD rats,
      the profile area of G cells also increased. There were no differences in
      nucleus/cell ratio due to alcohol ingestion alone, but it decreased significantly
      in PD and A-PD rats. Pale and lucent types of granules were predominantly seen in
      G-cells of animals of group A and A-PD. Mean diameter of granules increased in A,
      PD and A-PD rats. Other endocrine cells (ECL, D, EC) also decreased in number in
      A rats. Somatostatin producing D-cells decreased significantly in A-PD rats, both
      in fundic and pyloric mucosa.

PMID- 10085779
TI  - Behavioural alterations in rats induced by single prenatal exposure of
      haloperidol.
AB  - Haloperidol (50 mg/kg, i.p.) treatment was given once to two different groups of
      pregnant Charles Foster rats on gestational day 9 and 14, these being
      respectively the critical periods of neural morphogenesis and rapid neural cell
      proliferation in this species. Pregnant control rats were similarly treated with
      equal volume of vehicle. The pups born were subjected to open-field exploratory
      behaviour and elevated plus-maze behaviour tests of anxiety and learned
      helplessness test of depression at 9 weeks of age. The results indicate that
      prenatal haloperidol treatment on gestational day 14 induces a significant
      increase in open-field ambulation and faecal droppings whereas haloperidol
      treatment on gestational day 9 caused significantly decreased rearing and
      unaltered ambulation in rat offsprings. Rat offsprings treated with haloperidol
      on gestational day 9 and 14 also displayed significant anxiogenic behaviour
      pattern on elevated plus-maze. Significantly increased number of escape failures
      were observed in learned helplessness tests indicating presence of depression in
      haloperidol treated rat offsprings. These behavioural alterations were found to
      be more marked in rat offsprings treated with haloperidol on gestational day 14.
      The results suggest that prenatal single exposure of high dose of haloperidol
      during critical period of neural cell proliferation leaves a lasting imprint on
      offsprings resulting in abnormal emotional state.

PMID- 10085780
TI  - Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom prolongs
      repolarization time and refractoriness of the compound action potential of frog
      sciatic nerve in vitro through calcium dependent mechanism.
AB  - Effects of Indian red scorpion (M. tamulus concanesis; MBT) venom on the compound
      action potential (CAP) of sciatic nerve in vitro were examined. MBT venom (0.1
      6.0 micrograms/ml) prolonged the repolarization time and refractory period of the
      CAP in a concentration-dependent manner with maximal potentiation occurring at 6
      micrograms/ml (about 100-200 times of the initial). At 1 microgram/ml of venom
      the prolongations were 40-50 times the initial durations and this concentration
      was used for subsequent experiments. Rise time, threshold, and conduction
      velocity of CAP were not altered by MBT venom (1 microgram/ml). In Ca(2+)-free
      medium, the venom-induced prolongations were only 2-6 times the initial response
      but addition of Ca2+ in the same medium then prolonged than by 50-70 times. The
      Ca2+ channel antagonists (nifedipine, 10 microM or Mg2+ ions, 5 mM) attenuated
      the venom (1 microgram/ml)-induced prolongation of repolarization time and
      refractory period. However, venom-induced prolongation of CAP responses were
      still significantly greater than the control in presence of these antagonists.
      The results indicate that MBT venom-induced increases in repolarization time and
      refractory period of the action potential greatly depend upon the presence of
      Ca2+ ions in the medium. The Ca2+ influx was through the L-type of Ca2+ channels.

PMID- 10085781
TI  - Effect of 17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one on
      reproductive organs of the male laboratory mouse.
AB  - The effect of subcutaneous administration (10, 15 and 20 mg/kg body weight/day,
      for 21 days; and 20 mg/kg body weight/day, for 28 days) of 17 alpha-cyanomethyl
      17 beta-hydroxy- estra-4, 9-dien-3-one (STS 557) on the male reproductive organs
      of the Parkes strain mouse was investigated. The effect of the treatment on the
      testis was not uniform; both regressed and normal seminiferous tubules were
      observed in the same section of the organ. Furthermore, the histological changes
      observed in the seminiferous tubules in testes of STS 557--treated mice were not
      different in different dosage groups. In general, in moderately affected
      seminiferous tubules, the germinal epithelium was thin and consisted of Sertoli
      cells, spermatogonia, spermatocytes and spermatids; such tubules showed presence
      of many vacuoles in the epithelium. In severe cases, the tubules had collapsed
      and were lined by mainly Sertoli cells, spermatogonia and spermatocytes. The
      treatment also caused marked depression in motility and concentration of
      spermatozoa in cauda epididymidis, weight of accessory sex glands and in the
      levels of sialic acid and fructose in the epididymis and seminal vesicle,
      respectively. By 56 days of drug withdrawal, the alterations induced in the
      reproductive organs returned to control levels, suggesting that STS 557 treatment
      induces reversible alterations in the male reproductive organs of Parkes strain
      mouse.

PMID- 10085782
TI  - Bioinorganic study on [Fe(promethazine)2H2O Cl]2+ complex.
AB  - The coordination chemistry of iron (III) is the environment of an antihistaminic
      drug, promethazine has been explained to include a low spin, six-coordinate
      complex [Fe(Prometha)2(H2O) Cl] Cl2. Metaldrug interaction in vitro in aqueous
      KCl phase was studied polarographically at physiological pH and temperature. On
      the basis of elemental, magnetic, conductometric, IR, UV-visible, NMR
      spectroscopic analysis it is concluded that in solid phase two promethazine
      molecules with their N,N donor sites encompass the metal. Mass spectral study on
      the complex confirms that one of the three chlorides is involved in the
      coordination. The respective changes in the antihistaminic activity of the drug
      as a result of complexation has been determined and a possible mechanism is
      suggested.

PMID- 10085783
TI  - Temporal oscillations of phosphatases in N-phthaloyl gamma-aminobutyric acid
      treated rats.
AB  - N-pathaloyl gamma-aminobutyric acid (P-GABA) was administered to Wistar and 24 hr
      rhythms of acid and alkaline phosphatases were studied under light-dark
      conditions. P-GABA administration advanced the peak times of phosphatases. Since
      GABA is being involved in conveying dark information to the clock, exogenous
      administration of P-GABA might reduce the photic information received by the
      clock. The results could be explained by slight daily advances which would bring
      the peak times to the points 21 days after the start of administration.

PMID- 10085784
TI  - Effect of cigarette smoking on muscle strength of flexibility of athletes.
AB  - Kraus-Webber test which indicates muscle strength and flexibility of certain
      group of muscles showed significant decrease in cigarette smoking athletes in the
      age group of 19-30 years compared to nonsmoking athletes. The results indicate
      tobacco smoke inhalation affects muscle flexibility and strength required for
      athletes.

PMID- 10085785
TI  - Adaptive response to low dose of EMS or MMS in human peripheral blood
      lymphocytes.
AB  - Human peripheral blood lymphocytes stimulated in vitro for 6 hr were exposed to a
      low (conditioning) dose of ethyl methanesulfonate (EMS; 1.5 x 10(-4) M) or methyl
      methanesulfonate (MMS; 1.5 x 10(-5) M). After 6 hr, the cells were treated with a
      high (challenging) concentration of the same agent (1.5 x 10(-3) M EMS or 1.5 x
      10(-4) M MMS). The cells that received both conditioning and challenging doses
      became less sensitive to the induction of sister chromatid exchanges (SCEs) than
      those which did not receive the pretreatment with EMS or MMS. They responded with
      lower frequencies of SCEs. This suggests that conditioning dose of EMS or MMS has
      offered the lymphocytes to have decreased SCEs. This led to the realization that
      pre-exposure of lymphocytes to low dose can cause the induction of repair
      activity. This is a clear indication of the existence of adaptive response
      induced by alkylating agents whether it is ethylating or methylating in human
      lymphocytes in vitro.

PMID- 10085786
TI  - Immunopotentiating effects of Azadirachta indica (Neem) dry leaves powder in
      broilers, naturally infected with IBD virus.
AB  - Effects of feeding of powdered dry leaves of A. indica (AI) were investigated on
      humoral and cell mediated immune responses, in a flock of broilers which had
      survived an outbreak of infectious bursal disease (IBD). AI (2 g/kg) treatment
      significantly enhanced the antibody titres against new castle disease virus
      (NCDV) antigen and also potentiated the inflammatory reactions to 1. Chloro-2,4
      di- nitro benzene (DNCB) inskin contact test. The results indicate that AI could
      be beneficial in immunosuppressed condition like IBD, in poultry.

PMID- 10085787
TI  - Anti-oxidant effect of flavonoids on hemoglobin glycosylation.
AB  - A high glucose concentration has been found to lead to the glycosylation of amino
      groups of lysine residue in proteins. The addition of reducing agent not only
      prevents this reaction but also reverses it. On the other hand, flavonoids which
      found in plant sources have antioxidant properties. Since the glycosylation of
      protein is an oxidation reaction, therefore, antioxidants should be able to
      prevent this reaction. In this study, the best concentration and time to incubate
      glucose with hemoglobin was investigated. Then the glycosylation degree of
      hemoglobin in the presence of flavonoids and their absence was measured by means
      of a colorimetric method. Different concentration of flavonoids (Quercetin,
      Rutin, Kaempferol) were used. The preventing effect on hemoglobin glycosylation
      by the three concentrations; 0.5, 5, 10 micrograms/ml was estimated as follows:
      for Rutin; 11%, 27%, 42%, Quercetin; 3%, 37%, 52%, Kaempferol; 10%, 12%, 15%
      respectively. So, the in vivo effect should be investigated and then plants that
      containing flavonoids can be utilized to prevent or treat complication of
      diabetes.

PMID- 10085788
TI  - Lipid grafts of egg-box complex: a new supramolecular biovector for 5
      fluorouracil delivery.
AB  - An attempt was made to improve the pharmacokinetic behaviour of 5-fluorouracil (5
      FU) by incorporating it into lipoprotein imitating synthetic carrier
      'supramolecular biovector (SMBV)' which is an important prerequisite for
      achieving its better therapeutic performance against cancer. The polysaccharide
      core of SMBVs was prepared by ionotropic gelation technique by cross-linking
      polyguluronate units in the alginate molecules with calcium ions to form so
      called 'egg-box structure'. The formulation and process variables were optimized
      to obtain particles of nanometer size range. Hydrophobization was carried out by
      fatty-acylation on the surface followed by phospholipid coating. Palmitoyl
      polyethylene glycol (p-PEG) was anchored to impart stealth behaviour. The
      scanning electron microscopy showed discrete spheres of average diameter 748 nm.
      Polydispersity was estimated to be 0.37. Overall zeta potential was -21.3 mV. The
      drug loading capacity and encapsulation efficiency was found to be 10.0% and
      97.9%, respectively. The release from drug solution (AP) followed zero-order
      kinetics. Higuchi release pattern was obtained for egg-box complex cores (AP1)
      while first-order pattern was followed for fatty acylated (AP2) and lipid coated
      cores before (AP3) and after p-PEG anchoring (AP4). The amount of drug liberated
      in 24 h was in the order AP > AP1 > AP2 > AP4 > AP3. The release pattern obtained
      was a combined effect of drug diffusion through egg-box matrix as well as
      partitioning in hydrophobic layer and p-PEG layer around the SMBV. The stability
      study showed negligible leakage and no appreciable change in particle size upon
      storage at different temperatures which is an indication of good stability of
      SMBV formulation. The plasma clearance data revealed increase in circulation half
      life of drug and bioavailability. Tissue distribution data obtained was a result
      of competitive uptake of formulations from tissue macrophages and lymphatics
      depending upon its surface characteristics and residence period in vascular
      system. The enhanced delivery of drug to lymphatics and improvement in its half
      life render SMBVs useful for control of metastasis and tumour growth.

PMID- 10085789
TI  - In vitro study of the interaction between quinolones and polyvalent cations.
AB  - The aim of the present study was to evaluate the influence of aluminium and iron
      on the in vitro dissolution kinetics of ciprofloxacin and ofloxacin as well as
      the usefulness of this type of in vitro data to predict modifications in in vivo
      absorption processes as a consequence of different factors, such as the widely
      documented in vivo interaction between quinolones and cations. Fitting of
      experimental data to different theoretical in vitro dissolution profiles was
      performed by non-linear regression methods and the statistical moments were
      calculated from raw experimental data. Analysis of residuals applied to
      dissolution curves as well as statistical comparison of the estimated parameters
      were carried out to evaluate the in vitro interaction. The results reveal
      significative modifications of the dissolution profiles of these quinolones as a
      consequence of the presence of cations, especially for Fe2+ which decreases 34.7%
      the maximum amount dissolved for ciprofloxacin and 29.1% for ofloxacin. Al3+ also
      produces a decrease of the total amount of quinolone dissolved although less
      relevant than Fe2+. Analysis of residuals proved to be the best statistical
      method to evaluate differences between whole dissolution profiles, at least under
      the experimental conditions used.

PMID- 10085790
TI  - Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the
      rat.
AB  - The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week,
      was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po).
      Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from
      dosing, using a sensitive HPLC method. No significant changes were observed in
      the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0
      infinity) between the control and the pre-treated groups. The findings of this
      study suggest that OXC metabolism in the rat is apparently not affected by
      valproic acid, and the lack of effect may be attributed to the different pathways
      of biotransformation of the two drugs.

PMID- 10085791
TI  - Synthesis and pharmacological activity of thebaine-derived mu-opioid receptor
      agonists.
AB  - Thebaine-derived mu-opioid agonists were synthesized through the reaction of
      thebaine with N-aryl maleimide and tested for opioid activity. Morphine was used
      as reference compound. Our results show that an attachment of aryl succinimide
      group to thebaine produced series of compounds with mu-opioid agonist activity.
      The most active compound in smooth muscle preparation was compound 6 with an IC50
      ratio of delta/mu = 248.69 and was as potent as morphine with ED50 value 26.65 mg
      kg-1 i.p. in hot-plate test and showed good antinociceptive activity.

PMID- 10085792
TI  - The role of nebulized morphine in managing dyspnea.

PMID- 10085793
TI  - Jack Kevorkian: "too much"!

PMID- 10085794
TI  - The ABCs of bereavement volunteers: acquire, build, cherish.

PMID- 10085795
TI  - Minority access to hospice.
AB  - In recent decades, the hospice movement in America has experienced substantial
      growth, but there are still impediments preventing the majority of Americans from
      utilizing this type of care. Moreover, minority Americans experience greater
      barriers to the utilization of hospice care. Although there are positive trends
      to suggest utilization of hospice care by minorities may increase in the future,
      these factors need to be supported through strategies implemented by hospice
      administrators, providers, and volunteers.

PMID- 10085796
TI  - Issues and themes in the care of persons with Alzheimer's disease.

PMID- 10085797
TI  - Criteria for enrolling dementia patients in hospice: a replication.
AB  - Because survival time varies greatly in dementia, it is difficult for dementia
      patients to meet a key criterion for the Medicare Hospice Benefit, a six-month
      survival time. In a previous study, the authors examined guidelines for admitting
      dementia patients to hospice; the National Hospice Organization (NHO) guidelines
      were found to work well in identifying appropriate candidates for hospice among
      dementia patients. This was especially true for those patients whose deficits had
      progressed in an ordinal fashion consistent with Functional Assessment Staging
      (FAST) and who had reached stage 7C. The purpose of this study was to examine the
      utility of the NHO guidelines in identifying dementia patients who are
      appropriate for hospice; the limitations of these guidelines regarding non
      ordinal patients; and the importance of the actual care plans used--as opposed to
      our previous study, which only examined initial treatment plans. Forty-five
      dementia patients enrolled in Hospice of the Great Lakes in Illinois were studied
      longitudinally over two years; this included a follow-up period of at least six
      months for all patients. Measures included: survival time; FAST; a medical
      complications checklist, which consisted of common complications of end-stage
      dementia; and co-morbid medical conditions and aggressive care, which consisted
      of feeding tubes, antibiotics, and Foley catheters used during the course of the
      study. Patients who had reached Stage 7C at intake had a mean survival time of
      4.1 months; and the majority (71 percent) died within six months. Non-ordinal
      patients lived significantly longer at a mean of 10.9 months (p < .01), and and
      the minority (30 percent) died within six months. Foley catheters decreased
      survival time; and the use of antibiotics did not make a difference. This study
      echoed our previous findings regarding the usefulness of NHO guidelines in
      identifying dementia patients with a survival time of six months or less,
      specifically those at stage 7C or greater. The findings also suggest that the
      nature of the palliative care plan influences survival time.

PMID- 10085798
TI  - Breast cancer, colorectal cancer, and esophageal cancer.
AB  - This is the second of a six-part series on metastatic spread and natural history
      of 18 common tumors. Part one summarized symptom/problem anticipation, cancer
      metastasis, and the 18 tumors that each cause more than 6,000 deaths per year in
      the United States. Bladder and brain cancer were discussed, with information
      given on tumor types, metastatic spread and invasion, and common symptoms. Part
      two charts the natural histories of breast, colorectal, and esophageal cancers.
      Each of these cancers is presented separately, with information given on
      mortality rates, the most common tumor types, sites of metastases, common
      problems, and common oncologic emergencies. Sites of spread, resulting problems
      (including site-specific symptoms), and assessment parameters are presented as
      tables. Material is presented so that clinicians will be able to anticipate the
      spread of these cancers and thus identify problems early in their development so
      that the problems are more easily managed.

PMID- 10085799
TI  - Applying hospice principles in the palliative care debate.

PMID- 10085800
TI  - Nebulized opioids to treat dyspnea.
AB  - Breathlessness secondary to cancer and nonmalignant disease is very distressing
      and exhausting to patients and families. Patient quality of life and
      functionality can be greatly improved with effective management. The
      pathophysiology and treatment of dyspnea are where the science of pain management
      was 20 years ago. While the optimal therapy for dyspnea would be to treat the
      underlying cause, this is frequently not possible. Research results evaluating
      dosages and effectiveness of nebulized morphine are conflicting. Some researchers
      have reported dramatic benefit to patients in relieving the symptoms of dyspnea,
      increasing exercise endurance, and improving function. Other studies have
      reported no significant differences between nebulized morphine and saline with or
      without oxygen. Studies that administer single predetermined doses that are not
      titrated to relief in patients that do not have end-stage lung or cardiac disease
      may report false-negative results. Other factors such as the placebo effect of
      saline and oxygen, if not controlled, may cause false-positive results. The
      dramatic positive benefits documented warrant further investigation on the
      appropriate patient selection criteria and therapeutic potential. Clearly, large
      scale randomized trials on opioid nebulized treatments for patients with severe
      dyspnea need to be published to reach a clear consensus outlining efficacy and
      administration parameters. Until that time, we must rely on anecdotal reports for
      treatment options. Such reports of the effectiveness of nebulized morphine as an
      alternative to hospital or hospice admission are encouraging for patients and
      family members managing severe dyspnea in the home.

PMID- 10085801
TI  - Unlicensed assistive personnel: a key issue at the turn of the century.

PMID- 10085802
TI  - The new behaviors of innovation.

PMID- 10085803
TI  - Where will you be in the new millennium?

PMID- 10085804
TI  - A primer for nurse managers in managing those messy fluctuations in volume and
      intensity.

PMID- 10085805
TI  - Who owns a person's body organs after death?

PMID- 10085806
TI  - Facial surgery and children with Down's syndrome.

PMID- 10085807
TI  - Nursing assessment of patients with non-acute wounds.
AB  - Accurate and thorough assessment of patients with wounds is essential in order to
      provide correct treatment. In relation to patients with open, non-acute wounds,
      the areas that need assessing include general health and specific underlying
      disease process, care being given and local wound environment. This article
      outlines specific details of the assessment process. It includes a breakdown of
      factors affecting healing, a discussion of the importance of diagnosis of cause,
      an outline of factors within care provision that may have a negative effect on
      healing, and areas relevant to the wound itself that should be assessed.

PMID- 10085808
TI  - Inadvertent hypothermia prevention: the anaesthetic nurses' role.
AB  - Up to 90% of patients experience hypothermia perioperatively. Inadvertent
      hypothermia can have a profound physiological effect on the body, varying from
      mild vasoconstriction and feeling cold to cardiac arrest and death. Anaesthesia,
      general or regional, increases the risk as the normal protective reflexes such as
      shivering are absent, particularly when muscle relaxants are used. The very young
      and the elderly are particularly vulnerable. Preoperative assessment is
      essential. The greatest reduction in temperature occurs in the first hour of
      surgery, as a result of patient exposure, skin disinfection with cold fluids,
      inhalation of cold volatile gases and the administration of cold intravenous
      fluids, as well as exposure to cool theatre temperatures. If the theatre
      temperature drops below 21 degrees C, all patients will develop hypothermia.
      Patients lose heat through radiation, convention and conduction, with conduction
      having the greatest effect. Forced air warmers such as the Bair Hugger are the
      most effective means of preventing and treating heat loss. They should be used
      routinely although their contribution to infection also needs to be considered.
      Nurses should be aware of the risks of hypothermia so that modes of prevention
      can be employed to minimize the risks of inadvertent hypothermia.

PMID- 10085809
TI  - Update on clinical guidelines.

PMID- 10085810
TI  - Assessing children's spirituality: what is the way forward?
AB  - This article identifies the difficulties facing nurses working with the spiritual
      experiences of children. There is a lack of literature and education available in
      this field and as a consequence paediatric nurses are forced to use adult-based
      research. The benefits, as well as the drawbacks of this approach, are examined.
      In doing so it is hoped that the article might generate debate and discussion as
      to how to address this valued but under-investigated area of nursing practice.

PMID- 10085811
TI  - Should children with Down's syndrome have cosmetic surgery?
AB  - This article explores the rise in the uptake of cosmetic surgery for children
      with Down's syndrome. The pursuit of such surgical intervention is often a
      response to society's discriminatory attitude towards Down's syndrome and
      difference. Such an action raises many ethical concerns, e.g. should a child be
      subjected to cosmetic surgery when he/she does not understand what is happening
      to him/her? Much time, effort and resources are needed to work with children with
      Down's syndrome to ensure their full and active development through childhood.
      There have been changes in challenging discriminatory attitudes towards people
      with a disability in society. This, however, is the result of the public coming
      into contact and building relationships with people with disabilities in the
      wider community and not cosmetic surgery.

PMID- 10085812
TI  - HIV and combination therapy: meeting the challenge of a new era.
AB  - With the advent of combination therapy in the treatment of human immunodeficiency
      virus (HIV) infection, there has been a vast reduction in the number of people
      admitted to AIDS units as inpatients, and a marked improvement in the quality of
      life for people infected with HIV. Combination therapy comprises the combined
      administration of various powerful antiviral drugs to prevent CD4 cell
      destruction and minimize the chance of a rapidly replicating virus becoming
      resistant. This article presents an overview of the basic elements of this
      therapy, discussing some of the challenges that are a corollary of this new era.
      In particular, the implications of an extended period of survival and wellness
      for a group of people previously thought to be the victims of a strictly acute
      condition are addressed. These implications relate to therapeutic, psychological,
      employment, social and sexual issues. Finally, the issues facing carers (both lay
      and professional) are discussed.

PMID- 10085813
TI  - Brevet tx: anti-embolism stockings for prevention and treatment of DVT.
AB  - This article highlights the incidence and aetiology of thrombi, in particular
      deep vein thrombosis (DVT) before discussing the clinical features, diagnostic
      techniques and management of patients with suspected or confirmed DVT. The
      prophylactic use of anti-embolism stockings is then reviewed, including relevant
      clinical evidence, with particular reference to one of the leading brands of
      stocking currently available, that of Brevert tx (Seton Scholl Healthcare). The
      action, features, benefits and application of this type of anti-embolic stocking
      are detailed.

PMID- 10085814
TI  - Nurses in academic departments of general practice and primary care.
AB  - In 1997, the authors conducted a survey of registered nurses working in the
      academic departments of general practice and primary care in UK and Irish medical
      schools. The survey aimed to determine the number, demographic and professional
      profile of nurses employed in these academic departments, including their
      employment status and their views on their clinical work and professional
      development. The majority of nurses were professionally experienced, had higher
      degrees, worked in a research capacity, and were likely to have short-term
      contracts. Contrary to professional perceptions, the majority of nurses stated
      that clinical work is important to their current job and expressed a need for
      research support and recognition of their autonomy as healthcare professionals.

PMID- 10085815
TI  - A nursing 'peace' vs the medical 'war' model.

PMID- 10085816
TI  - Laparoscopic Swenson Pull-through Procedure for Hirschsprung's Disease.
AB  - The introduction of a new procedure into the operating room is always a challenge
      that requires careful planning and teamwork. This article describes the
      pathophysiology of Hirschsprung's Disease, the perioperative nursing care
      required and the operative technique of the Laparoscopic Swenson Pull-Through
      Procedure.

PMID- 10085818
TI  - Perioperative registered nurses are essential to quality patient care in the
      operating room. Mission statement. Operating Room Nurses Association of Canada.

PMID- 10085819
TI  - Strategies to deal with change. Saskatchewan Operating Room Nurses Group.

PMID- 10085820
TI  - Seeing the light in day surgery.

PMID- 10085821
TI  - Planned change in the evolution of cataract surgery.
AB  - The subject of this paper is a description of how perioperative nurses and other
      health care professionals worked together to meet the demands of change. New
      technologies and new techniques in cataract surgery with lens replacement has
      decreased dramatically the amount of operating room (OR) time required. With the
      reduction in OR time, the process of moving cataract patients through the
      perioperative experience became chaotic. Change was necessary. Planned change and
      teamwork made the change process less chaotic and more rewarding.

PMID- 10085822
TI  - Nurses, at the bedside and the ballot box.

PMID- 10085823
TI  - A call for nursing to be united.

PMID- 10085824
TI  - The origins of casualty evacuation and echelons of care: lessons learned from the
      American Civil War.
AB  - The American Civil War produced many victims of battle who challenged the medical
      community. Not long after the war started the medical community was forced to
      make rapid, significant changes in how soldiers were evacuated, how they were
      cared for both immediately and long-term, and how the spread of fatal infectious
      diseases was controlled. This was the era in which nurses proved their importance
      and became a permanent segment of trauma care.

PMID- 10085825
TI  - Youth Alternative Sentencing Program: a description and evaluation of an alcohol
      and marijuana intervention program.
AB  - An alternative program was designed for youth who were charged with an alcohol or
      marijuana offense in San Bernardino County, California. In place of a conviction,
      the youth could attend an extended educational program that emphasized their
      ability to change behavior and to understand the consequences of risk-taking
      behavior. An evaluation was completed by the participants, demonstrating that
      this population of youth began to experiment with alcohol and marijuana around 12
      and 13 years of age. A large number of youths were identified for nontraffic
      offenses, which offered an opportunity to intervene before members of this
      population become involved in a motor vehicle crash.

PMID- 10085826
TI  - Use of evidence-based practice management guidelines in trauma care.
AB  - A PMG is a tool developed by a consensus process, with the input of all trauma
      care practitioners who are involved in the care of a patient with a specific
      clinical issue. The group that develops the PMG uses current, evidence-based
      data, carefully introduces and monitors the PMG in the clinical setting, and
      evaluates the success of the PMG in accomplishing the goals identified at the
      beginning of the process. The ultimate goal of a PMG is to eliminate unnecessary
      practice variations, with the end point of achieving quality care. Participating
      in the development of a guideline with a review of the literature serves as an
      excellent educational process for all practitioners.

PMID- 10085827
TI  - Medical device adverse events and electromagnetic interference.

PMID- 10085828
TI  - An analysis of medication errors: look alike and sound alike names.

PMID- 10085829
TI  - DERMABOND topical skin adhesive.

PMID- 10085830
TI  - Just do it!

PMID- 10085831
TI  - The importance of pediatrics.

PMID- 10085832
TI  - Newborn hypoglycemia.
AB  - Neonatal hypoglycemia is a common problem encountered by both term and preterm
      infants. It can be either symptomatic or asymptomatic. Prolonged hypoglycemia may
      result in permanent neurologic impairment and death. Definitions of hypoglycemia
      vary and remain controversial. Underlying causes of hypoglycemia include (a)
      inadequate glucose production; (b) increased glucose utilization; (c)
      abnormalities of endocrine regulation; and (d) other causes. Nurse practitioners
      must be aware of infants at risk for hypoglycemia so they can provide appropriate
      interventions. In this article the clinical characteristics of hypoglycemia are
      reviewed, various causes for hypoglycemia are identified, and an infant with
      prolonged hypoglycemia is described. In addition, the role of the nurse
      practitioner in the care and management of these infants is addressed.

PMID- 10085833
TI  - Think of genetic hypercalciuria when a child has urinary tract findings.
AB  - Genetic hypercalciuria, one of the most common mineral disorders in childhood, is
      frequently associated with a variety of urinary tract problems. Identifying and
      treating genetic hypercalciuria alleviates urinary tract problems and optimizes
      peak bone mass growth in affected children. Advanced practice pediatric nurses
      play a key role in identifying and coordinating care for children with genetic
      hypercalciuria.

PMID- 10085834
TI  - Aberrant genital practices: an unrecognized form of child sexual abuse.
AB  - The sexual abuse of children in the United States is a problem of epidemic
      proportions. Sexual abuse is defined as any activity with a child that is
      conducted for the sexual gratification of the perpetrator. Common examples of
      sexual abuse include vaginal intercourse; oral-genital contact; anal-genital
      contact; fondling; finger manipulation; and stimulation of the offender. Sexual
      abuse may also occur in less typical patterns in which children are subjected to
      aberrant genital care practices, typically by their parents. Three case studies
      illustrate examples of aberrant genital practices. This type of abuse can be
      identified in primary care settings by asking specific questions of parents and
      children. Examples of such questions are provided.

PMID- 10085835
TI  - Children's responses to sequential versus simultaneous immunization injections.
AB  - INTRODUCTION: The purpose of this study was to compare distress behaviors and
      perceptions of distress in 4- to 6-year-old children who received two
      immunization injections simultaneously with those in children who received their
      immunizations sequentially. METHOD: This experimental study used a convenience
      sample of 46 children scheduled for pre-kindergarten examinations. The children
      were randomly assigned to either a sequential injection or a simultaneous
      injection group. Direct observation and videotapes were made of the children's
      behaviors before and after injection. Distress behaviors were analyzed with the
      Observation Scale of Behavioral Distress-Revised, and perceptions of distress
      were obtained from both children (with the Wong-Baker Pain Rating Scale [FACES])
      and parents (with the Visual Analog Scale). RESULTS: Results of the Observation
      Scale of Behavioral Distress-Revised showed no significant differences in
      children's distress behaviors between the two groups either before or after
      injection. The children's self-reports of distress also showed no group
      differences. Parents' perceptions of the children's distress before and after
      injection were lower for the sequential group but were judged to be unrelated to
      the intervention. Given the opportunity to state a preference, however, parents
      preferred the simultaneous method. DISCUSSION: The simultaneous procedure was not
      found to be associated with reduced distress behaviors; however, parents
      preferred the simultaneous method.

PMID- 10085836
TI  - School-age children's fears, anxiety, and human figure drawings.
AB  - INTRODUCTION: The purpose of this study was to identify the fears of school-age
      children and determine the relationship between fear and anxiety. METHOD: A
      descriptive, correlational, secondary analysis study was conducted using a
      convenience sample of 90 children between the ages of 8 and 12 years. Each child
      was instructed to complete the Revised Children's Anxiety Scale and then answer
      questions from a structured interview. On completion, each child was instructed
      to draw a human figure drawing. Frequency charts and correlational statistics
      were used to analyze the data. RESULTS: Findings indicated that the most
      significant fears of the boys were in the categories of animals, safety, school,
      and supernatural phenomena, whereas girls were more fearful of natural phenomena.
      High correlations existed between anxiety scores and the number of fears and
      emotional indicators on human figure drawings. DISCUSSION: Because human figure
      drawings are reliable tools for assessing anxiety and fears in children,
      practitioners should incorporate these drawings as part of their routine
      assessments of fearful children.

PMID- 10085837
TI  - Toddler's diarrhea.

PMID- 10085838
TI  - Growth and development: affectionate behavior.

PMID- 10085839
TI  - Management of asymptomatic term neonates born to mothers with group B
      streptococcus.

PMID- 10085840
TI  - Boy with a facial rash. Erysipelas.

PMID- 10085841
TI  - Nurse practitioners win protections in Nurse Education Act reauthorization.

PMID- 10085842
TI  - The "texture" of practice: a plea for more qualitative research.

PMID- 10085843
TI  - A 1996 NASN research award winner. Health services provided by school nurses for
      students with chronic health problems.
AB  - Increased numbers of students are entering schools with chronic health problems
      and in need of nursing and other health services. Some studies have been
      conducted in recent years describing nursing practice in schools. However,
      further study of school nursing practice was warranted owing to two major
      problems. The first was limited financial resources to provide needed nursing
      services. The second was inadequate documentation of both the health needs of
      students and current school nursing practice in meeting those needs. The purpose
      of this descriptive study was to examine the nature and extent of nursing
      services provided in the schools in the late 1990s and to identify potentially
      reimbursable nursing services being provided to students with chronic health
      problems. A survey was mailed to active members of the School Nurse Organization
      of Minnesota (SNOM). The findings indicated the considerable diversity in the
      practice setting as well as the large volume of nursing services being delivered
      in schools. Results will be essential in the acquisition of financial resources,
      including collaboration with third-party payors for reimbursement of nursing and
      other health services.

PMID- 10085844
TI  - The 1997 NASN research award winner. School nurses' perceptions of their
      interactions with nurse practitioners.
AB  - Relationships between traditional school nurses and nurse practitioners were
      studied using a descriptive research design. The study analyzed school nurses'
      perceptions of their professional interactions with nurse practitioners. A
      researcher-developed questionnaire was sent to 500 Missouri school nurses living
      in zip-code areas known to employ a high concentration of nurse practitioners. Of
      the 295 school nurses who responded, 148 had interacted professionally with a
      nurse practitioner in the previous 5 years. Analysis of the responses indicated
      an overall positive regard for the nurse practitioner role. Data from this study
      will be used to support and further improve working relationships between these
      two nursing specialty groups.

PMID- 10085845
TI  - Sickle cell disease: problem solving/coping methods among affected children and
      their non-affected siblings.
AB  - A small group of children with sickle cell disease and their non-affected
      siblings served as participants in a descriptive research project designed to
      describe how these children problem-solve and cope with social and academic
      stress at school. Data collection involved pictorial stimuli to evoke story
      telling. The study's results indicate that both problem-solving and coping
      methods were identical between affected and non-affected children in the sample:
      both groups utilized direct action in dealing with stressful situations. The
      study's generalizability is limited on account of small sample size.

PMID- 10085846
TI  - Medications for early onset bipolar illness: new drug update.
AB  - The diagnosis and treatment of children and adolescents with Early Onset Bipolar
      Disorder (EOBD) constitutes one of the more controversial areas of child
      psychiatry today. Diagnosis is problematic because of overlapping symptom
      profiles with other childhood psychiatric disorders, some of which may be
      occurring co-morbidly. Attempts to deal with problematic behavioral patterns
      often lead to students receiving multiple psychotropic medications in addition to
      the mainstays of bipolar treatment, namely, mood stabilizers or thymolytics. The
      school nurse plays an important role in helping to identify and record behaviors
      which can assist in clarifying diagnoses and in monitoring responses to
      medications. The nurse's participation in educating and assisting these students
      to understand and optimize their drug therapy is critical to positive therapeutic
      outcomes.

PMID- 10085847
TI  - Can this be what our forefathers had in mind? The Massachusetts experience.
AB  - Political action is foreign to most school nurses, but it becomes more and more
      important as school nursing and school health become more complex. Sufficiency of
      services must be aggressively pursued through the legislative process. This
      article is a description of efforts to date to fund a nurse in every school in
      the Commonwealth of Massachusetts.

PMID- 10085848
TI  - Highway to health: on-line health education.
AB  - The TeleHealth Project is a model telecommunications program that provides health
      education and consultation on the Internet. The TeleHealth Project delivers
      health information to rural ninth-grade students and their communities on the
      North Carolina Information Highway through interactive distance learning. The
      "trip" is a two-way adventure for students, educators, and health professionals.
      The Eastern Area Health Education Center (EAHEC), associated with East Carolina
      University (ECU) in Greenville, North Carolina, produces the TeleHealth Program.
      This collaborative model was built on prior successful relationships between the
      school system and EAHEC, and university faculty who had worked on
      interdisciplinary projects related to adolescents and the professional
      preparation of health providers in school settings.

PMID- 10085849
TI  - Nurse-physician collaboration.
AB  - The literature indicates that collaboration between nurses and physicians has
      become more sophisticated as these relationships have become collegial in nature
      and as nurses have become assertive, autonomous, and accountable. On an
      individual level, physicians and nurses now entering collaborative relationships
      are successful at minimizing the obstacles of turf and territoriality as well as
      at managing practice boundaries. However, both need to consciously examine their
      patterns of communication in order to effect clinical interaction styles that
      maintain unequal or hierarchical relationships. Studies of interprofessional
      communication, including style of clinical interaction, conflict resolution, use
      of humor, and negotiation, contribute support for nurses and physicians in
      collaborative relationships (Balzer, 1993; Campbell, Mauksch, Neikirk, &
      Hosokawa, 1990; Feiger & Schmitt, 1979; Lenkman & Gribbins, 1994; Pike, 1991).
      Research on differences in health outcomes of patients cared for in the
      traditional and collaborative models of health care delivery, identification of
      the unique product of collaborative practice models, and further identification
      of the type of attitudinal climate in which collaborative relationships can be
      nurtured should be undertaken if the elusive nature of collaboration is to be
      captured (Siegler, Whitney, & Schmitt, 1994). Providing collaborative,
      interdisciplinary clinical experiences for students, as well as role modeling of
      collaborative relationships in nurse-physician faculty practice, can contribute
      to a greater understanding and acceptance of each professional's role in health
      care delivery (Campbell, 1993; Forbes & Fitzsimons, 1993; Larson, 1995).
      Tradition and professionalism and progressive concern about practice boundaries
      continue to be obstacles to collaborative practice. These need to be addressed by
      medical and nursing professionals on the institutional level and in the political
      arena. Collaboration between nurses and physicians need not remain only a
      researchable issue; its viability and vitality are crucial to the changing health
      care scene. Understanding the issues that affect collaboration, as well as the
      historical background in which it has developed, can help nurses and physicians
      in their joint effort to improve health care delivery.

PMID- 10085850
TI  - Smoking cessation tips: family system and addiction perspectives.

PMID- 10085851
TI  - Emerging roles for the gerontological nurse practitioner.

PMID- 10085852
TI  - Pharmacologic management of migraine.

PMID- 10085853
TI  - Disability information on the Internet.

PMID- 10085854
TI  - Differentiating prostate disorders.

PMID- 10085856
TI  - 1998 research and clinical presentation awards: American Academy of Nurse
      Practitioners.

PMID- 10085855
TI  - Virginia Trotter Betts, MSN, JD, RN, FAAN, Senior Advisor on Nursing and Policy
      to the Secretary and Assistant Secretary of Health and Human Services. Interview
      by Jan Towers and Carole Jennings.

PMID- 10085857
TI  - The readability of printed education materials regarding hormone replacement
      therapy.
AB  - In summary, HRT is a preventative medication that has been shown to decrease the
      incidence of heart disease and osteoporosis. It also has been shown to reduce
      symptoms of menopause and to increase the quality of life of users. Choosing to
      begin and maintain HRT is a personal and complicated decision. In evaluating the
      risks and benefits of HRT for any one woman, that woman and her primary care
      provider must individualize her past and current medical history, her family
      history, and her lifestyle. Together they must come to a decision that best
      represents the health, social needs, and desires of the patient. Individualizing
      HRT is difficult for a woman to do on her own, and it is time-consuming for a
      practitioner. Using PEMs to clarify the benefits and risks of HRT can be very
      beneficial to a woman considering such therapy. PEMs, however, are not a
      substitute for one-on-one education, and especially are not appropriate for
      teaching if their level of technical difficulty is beyond the scope of a
      patient's comprehension. This study suggests that many of the PEM's provided to
      women on the subject of HRT are failing to reach their target audiences because
      of their level of reading difficulty. A stated objective identified in the
      national initiative Healthy People 2000 (U.S. Department of Health and Human
      Services, 1997) is to "Increase to at least 90% the proportion of perimenopausal
      women who have been counseled about the benefits and risks of hormone replacement
      therapy for the prevention of osteoporosis." PEMs are one way to reach this
      objective, provided they are understandable to the clientele of focus.

PMID- 10085858
TI  - Validating a short acculturation scale for Filipino-Americans.

PMID- 10085859
TI  - Challenges of establishing a nursing center in rural eastern Oregon.
AB  - The success of the center, in fact its very existence, is the result of
      cooperation among many persons and agencies. Financial gifts, loans and grants
      have given the clinic a three-year time period to learn valuable lessons on how
      to organize for self-sufficiency. Staff have learned how to market to increase
      patient visit and have obtained Federal Rural Health Clinic status which will
      increase revenues substantially. Nurse Practitioners are learning appropriate
      visit coding and hold regular brainstorming meetings to develop creative business
      opportunities to assure financial stability. As a result of these experiences,
      the NP faculty have been able to design learning experiences for the nurse
      practitioner students which introduce them to entrepreneurial realities.
      Challenges are being met by the NPs in this rural practice which require vigor,
      creativity, and vigilance. Once the center reaches the level of self-sufficiency,
      it is the intent of the community to build a facility which can support a
      significant increase in patient load and still have room for other social and
      health services to operate within the facility. Bridges to the medical community
      are being strengthened through better communication and more community
      involvement. Educating the public and the medical community about the role of
      nurse practitioners and the broad base of nursing centers is a continual
      challenge for both faculty and students at the School of Nursing.

PMID- 10085860
TI  - Computer-based office messaging and fax.

PMID- 10085861
TI  - Diagnosis and management of acute pancreatitis.
AB  - Many aspects of acute pancreatitis treatment have been controversial, but with
      the refinement of contrast enhanced computed tomography, advances have been made
      towards quicker diagnosis and treatment of this condition. The management of this
      disease process for complication, and determination of cause so those future
      occurrences may be prevented.

PMID- 10085862
TI  - Clarifying nurse practitioners' unique contributions: application of the Shuler
      Nurse Practitioner Practice Model.
AB  - Even though nurse practitioners (NPs) have been widely accepted as members of the
      health care team for more than 30 years, their unique contributions in health
      care delivery are still unclear. It is critical that NPs collectively define
      their role, which is a blend of nursing and medicine, and consistently adhere to
      a model that defines practice parameters. This article proposes use of The Shuler
      Nurse Practitioner Practice Model as the critical missing link needed to guide
      NPs toward the demonstration of their unique contributions.

PMID- 10085863
TI  - Depression in the elderly: a review.
AB  - Although there is a plethora of literature regarding depression in the elderly,
      recognition of its existence remains a primary problem. Recognizing depression is
      paramount in the elderly. There is significant mortality and morbidity associated
      with elderly depression. The assumption that depression is a normal aging process
      must be changed. This should be done by educating the public and the
      practitioner. Appropriate screening tools should be administered on a regular
      basis regardless of the reason the elderly person is seeking care. These would
      include the Mini-Mental State Examination and a depression scale of the
      practitioner's choice. Baseline information should be gathered in order to
      provide data for further examination and continuity of care. This would be
      beneficial to determine the presence of a decline in either mental or cognitive
      states. There is evidence of gaps in the research related to depression in the
      elderly. Studies related to cognition and depression have contradictory results.
      Various limitations in the studies, such as sample size and the presence of
      cognitive impairment prior to the study, could account for this. Replication of
      these studies and further research in cognition and depression in the elderly is
      warranted.

PMID- 10085864
TI  - Alaska nurse practitioners' and physician assistants' perceptions of the
      collaboration process.
AB  - In summary, the findings suggest that NPs and PAs have a common perception of the
      collaboration process, and most participants engaged in more collaborative
      behaviors rather than less. The results can serve as an introduction to studying
      collaborative interactions between NPs and PAs. Such collaborative efforts have
      the potential to optimize patient care and increase respect, trust, and
      communication between the two professions.

PMID- 10085865
TI  - Voice recognition software for clinical use.
AB  - The current generation voice recognition products truly offer the promise of
      voice recognition systems, that are financially and operationally acceptable for
      use in a health care facility. Although the initial capital outlay for the
      purchase of such equipment may be substantial, the long-term benefit is felt to
      outweigh the expense. The ability to utilize computer equipment for educational
      purposes and information management alone helps to rationalize the cost. In
      addition, it is important to remember that the Internet has become a substantial
      source of information which provides another functional use for this equipment.
      Although one can readily see the implication for such a program in clinical
      practice, other uses for the program should not be overlooked. Uses far beyond
      the writing of clinic notes and correspondence can be easily envisioned.
      Utilization of voice recognition software offers clinical practices the ability
      to produce quality printed records in a timely and cost-effective manner. After
      learning procedures for the selected product and appropriately formatting word
      processing software and printers, printed progress notes should be able to be
      produced in less time than traditional dictation and transcription methods.
      Although certain procedures and practices may need to be altered, or may preclude
      optimal utilization of this type of system, many advantages are apparent. It is
      recommended that facilities consider utilization of Voice Recognition products
      such as Dragon Systems Naturally Speaking Software, or at least consider a trial
      of this method with one of the limited-feature products, if current dictation
      practices are unsatisfactory or excessively costly. Free downloadable trial
      software or single user software can provide a reduced-cost method for trial
      evaluation of such products if a major commitment is not felt to be desired. A
      list of voice recognition software manufacturer web sites may be accessed through
      the following: http://www.dragonsys.com/
      http://www.software.ibm/com/is/voicetype/ http://www.lhs.com/

PMID- 10085866
TI  - Differential diagnosis of headache.

PMID- 10085867
TI  - Integrative therapies in primary care practice.

PMID- 10085868
TI  - Herniated lumbar discs: diagnosis and management.

PMID- 10085869
TI  - Acute ischemic stroke.
AB  - To optimize the recovery outcome of those with acute ischemic stroke, several
      steps need to be taken and strengthened by the public and medical personnel.
      These include immediate identification of stroke symptoms and appropriate
      actions, quick access to EMS, rapid EMS response, treatment and evacuation, early
      communication to the medical facility, rapid diagnosis and interventions,
      specialized treatment, evaluation of complications, precipitating and
      accompanying factors, and appropriate rehabilitation when applicable.

PMID- 10085870
TI  - Factor V Leiden mutation: a nursing perspective.
AB  - The factor V Leiden mutation is a recently described autosomal dominant genetic
      risk factor for venous thromboembolism (VTE). Persons who are heterozygous or
      homozygous for this disorder are at 4 to 7 times and 50 to 100 times increased
      risk, respectively, for VTE. In particular, women have unique challenges because
      the presence of the Leiden mutation in combination with pregnancy or use of oral
      contraceptives results in an even greater increased risk for VTE. This article
      will review the factor V Leiden mutation, its association with VTE, and the
      genetic inheritance pattern and ethnic distribution. Oral contraceptive use,
      pregnancy, and hormone replacement therapy in women with the Leiden mutation will
      be discussed. Screening issues and management for all patients, and women in
      particular, will be addressed. Nursing implications for care management of this
      group of patients is complex and requires evaluation of the significance of newly
      defined genetic disorders such as the factor V Leiden mutation. Nurses need to be
      knowledgeable about genetic screening, risk factors, risk-reduction counseling,
      and considerations for long-term therapy, which include quality of life issues.
      Two case studies exemplify many of the issues that will be discussed.

PMID- 10085871
TI  - Alternative imaging techniques in vascular surgery.
AB  - Progress in vascular surgery has led to the need for more sophisticated methods
      of imaging the vascular system. Although conventional contrast angiography is
      still the primary method of visualizing the vascular system, it has problems and
      limitations that occasionally render it unsafe or inadequate. When conventional
      angiography cannot provide the needed information, 3 newer imaging methods--3
      dimensional (3-D) spiral computed tomographic scanning, computed tomographic
      angiography, and magnetic resonance angiography--are being used more widely to
      supplement or replace contrast angiography. The advantages, disadvantages, and
      clinical application of each method will be described. These methods have
      fundamentally changed the practice of vascular surgery and a thorough knowledge
      of them is essential.

PMID- 10085872
TI  - Incidence of thrombosis in pregnancy and postpartum: a retrospective review in a
      large private hospital.
AB  - This article addresses a 10-year retrospective chart review that was conducted at
      St John's Mercy Medical Center in St Louis, Mo, to investigate the incidence and
      prevalence of deep vein thrombosis in pregnancy and during the postpartum period.
      A total of 65,912 deliveries occurred between 1985 and 1995, and 105 (0.2%)
      patients were diagnosed with a deep vein thrombosis or superficial vein
      thrombosis during pregnancy or during the postpartum period. The study compared
      specific demographic data of the patients, and the differences in diagnostic
      testing, obstetric and medical history, methods of treatment, and sequela of
      patients, as well as the nursing implications.

PMID- 10085874
TI  - Sending a different message.

PMID- 10085873
TI  - Vascular nurse practitioner: development of an innovative role for the 21st
      century.
AB  - In the current health care environment, innovative roles are emerging for acute
      care nurse practitioners to provide care to increasingly complex patients. The
      roles are characterized by the provision of unique care that is comprehensive,
      cost-effective, efficient, and accessible. In this article, the development of
      the role of the vascular nurse practitioner in the acute care setting is
      explored. Practice privileges, practice agreements, and a model for delivering
      care are discussed.

PMID- 10085875
TI  - Documenting an adverse incident.

PMID- 10085876
TI  - Choosing the right vascular access device, Part I.

PMID- 10085877
TI  - Exposure safety. When the eyes have it.

PMID- 10085878
TI  - Myths & facts ... about diabetes mellitus.

PMID- 10085879
TI  - Adverse drug reaction. Pemoline and dyskinesia.

PMID- 10085880
TI  - Actionstat. Ruptured diaphragm.

PMID- 10085881
TI  - Atrial fibrillation. Soothing the savage beat.

PMID- 10085882
TI  - Minimizing the threat of C. difficile.

PMID- 10085883
TI  - Sam was an emotional terrorist--and he victimized everyone within earshot.

PMID- 10085884
TI  - Nurses. Are we still eating our young?

PMID- 10085885
TI  - New drugs99, Part II.

PMID- 10085887
TI  - Multitasking made easy.

PMID- 10085886
TI  - A tip of the cap to intermittent infusions.

PMID- 10085888
TI  - Earning my stripes.

PMID- 10085889
TI  - Help the Aged thinks that your age can make a detrimental difference to your
      care.

PMID- 10085890
TI  - A matter of policy. Interview by Nick Lipley.

PMID- 10085891
TI  - Educating teacher.

PMID- 10085892
TI  - Do you know best?

PMID- 10085893
TI  - Weight watchers.

PMID- 10085894
TI  - Men's health: more than some of his parts.

PMID- 10085895
TI  - Happy homes.

PMID- 10085896
TI  - Old age provides new problems.

PMID- 10085898
TI  - A blueprint for Europe.

PMID- 10085897
TI  - Striking a chord.

PMID- 10085899
TI  - Bully off!

PMID- 10085900
TI  - The visit. Interview by Alan Powell.

PMID- 10085901
TI  - Developing nurse endoscopy through re-engineering.
AB  - Innovative developments in nursing roles have been one of the benefits of re
      engineering at The Leicester Royal Infirmary NHS Trust. In the third in a series
      of four reports, the author describes nursing innovation in endoscopy.

PMID- 10085902
TI  - Challenging discrimination against disabled patients.
AB  - This article explores disturbing evidence that health professionals sometimes
      discriminate against disabled people in their care. Definitions and models of
      disability are examined with underlying beliefs about what 'disability' is. The
      author highlights some good practice and suggests positive ways in which nurses
      can challenge discrimination on the grounds of disability.

PMID- 10085903
TI  - Preparing assessors for continuous assessment.
AB  - Student nurses are continuously assessed during their common foundation programme
      to establish their clinical competence. But, as this study shows, many
      practitioners feel ill-prepared to play the part of assessor; students also
      identify this inadequacy.

PMID- 10085904
TI  - Health promotion: ensuring the health of the nurse.
AB  - This article describes how health promotion to maintain the health of the nursing
      workforce is equally important as activities for patients.

PMID- 10085905
TI  - Paediatric nursing recruitment focus. Part 2. In the community.

PMID- 10085906
TI  - Nurses wanted.

PMID- 10085907
TI  - Hard lessons.

PMID- 10085908
TI  - A shift in the law.

PMID- 10085909
TI  - Why I left the NHS.

PMID- 10085910
TI  - Breast practice.

PMID- 10085911
TI  - Time for reflection.

PMID- 10085912
TI  - Pay attention.

PMID- 10085913
TI  - Fit to eat.

PMID- 10085914
TI  - Primary care groups--are nurses on board?

PMID- 10085915
TI  - Do you feel alright?

PMID- 10085916
TI  - Parrish counsel. Interview by Ian McMillan.

PMID- 10085917
TI  - Shared ethical principles for everybody in health care.
AB  - In this report the authors introduce the first step in discussing a shared code
      of ethics across all medical disciplines. The Tavistock Group has published a
      shared statement of ethical principles, and June Andrews, RCN Scottish secretary,
      provides a commentary.

PMID- 10085918
TI  - A shared statement of ethical principles.
AB  - A multidisciplinary group recently came together at Tavistock Square in London in
      an effort to prepare a shared code of ethics (pages 32-33), reproduced here in
      full with an accompanying commentary by June Andrews, RCN Scottish secretary.

PMID- 10085919
TI  - Nurse-led outpatient treatment of deep vein thrombosis.
AB  - Patients with a deep vein thrombosis (DVT) have, historically, been treated
      initially with intravenous, unfractionated heparin, necessitating inpatient care.
      The advent of low molecular weight heparin (LMWH) now allows treatment of these
      patients on an outpatient basis, as the authors explain here.

PMID- 10085920
TI  - Anorexia nervosa: a cognitive-behavioural approach.
AB  - People with anorexia nervosa can be resistant to treatment because they do not
      feel the therapist is on their side. This article focuses on the need to
      establish a therapeutic relationship before interventions can begin. The author
      also outlines important factors in the onset and maintenance of anorexia nervosa.

PMID- 10085921
TI  - Dehydration and electrolyte disturbance.
AB  - This article discusses the nurse's role in the treatment and prevention of
      dehydration and electrolyte imbalance.

PMID- 10085922
TI  - Intensive care.

PMID- 10085923
TI  - Speak for yourself.

PMID- 10085924
TI  - Past, present and future.

PMID- 10085925
TI  - Blowing the whistle.

PMID- 10085926
TI  - Surprise, surprise.

PMID- 10085927
TI  - Degree of success.

PMID- 10085928
TI  - Power to the people.

PMID- 10085929
TI  - Good vibrations.

PMID- 10085930
TI  - The reunion.

PMID- 10085931
TI  - War and peace.

PMID- 10085932
TI  - A new start in Estonia.

PMID- 10085933
TI  - Issues in training and development.
AB  - In the last report in this series describing re-engineering at The Leicester
      Royal Infirmary NHS Trust, the implications of a re-engineered patient process on
      the training and development of staff are discussed.

PMID- 10085934
TI  - A review of 100 applications of section 5(4) Mental Health Act.
AB  - Section 5(4) of the Mental Health Act (1983) allows nurses to detain a
      psychiatric inpatient for up to six hours before a doctor arrives. This article
      reviews the use of Section 5(4) in 100 cases in North Cheshire between 1985 and
      1992. Doctors supported every nurse's decision to detain a patient. Patients
      detained under Section 5(4) were more likely to be converted to other sections.
      This suggests that the nurse's decision to detain the patient is a useful
      predictor of outcome.

PMID- 10085935
TI  - A nurse-led clinic for managing venous leg ulcers.
AB  - There is no shortage of research on wound care, particularly the care and
      management of venous leg ulcers. However, care is often fragmented and patients
      do not always receive treatment based on the latest evidence. This paper
      describes the establishment of a nurse-led leg ulcer clinic in a day hospital.
      The author has found reflective practice helpful in setting up this service.

PMID- 10085936
TI  - Compression bandaging.
AB  - This article discusses the different techniques that should be used for
      compression bandaging.

PMID- 10085937
TI  - New opportunities in community mental health.

PMID- 10085938
TI  - A pay rise of 11%.

PMID- 10085939
TI  - Not time to celebrate.

PMID- 10085940
TI  - Lifestyles of the famously not so rich.

PMID- 10085941
TI  - Is a single spine chilling?

PMID- 10085942
TI  - The knives are out for P2000.

PMID- 10085943
TI  - Too clever to care?

PMID- 10085944
TI  - A room of your own.

PMID- 10085946
TI  - Obsession with class is holding us back.

PMID- 10085945
TI  - Why nurses are more at risk than these bouncers.

PMID- 10085947
TI  - Bedside manner misses the point.

PMID- 10085948
TI  - Mother's pride.

PMID- 10085949
TI  - Trailblazers.

PMID- 10085950
TI  - Outlook sunny.

PMID- 10085951
TI  - Derided we fall....

PMID- 10085952
TI  - Mass immunisation: for and against.

PMID- 10085953
TI  - Mass immunisation: for and against.

PMID- 10085954
TI  - The battler of Hastings. Interview by Robert Munro.

PMID- 10085955
TI  - Mortgages.

PMID- 10085956
TI  - Ok computer.

PMID- 10085957
TI  - NT/3M National Nursing Awards. Home advantage.

PMID- 10085958
TI  - Giving a blanket bath--2.

PMID- 10085959
TI  - Confidence tips.

PMID- 10085960
TI  - Brain tumours.

PMID- 10085961
TI  - Helping the grieving process: a nurse's story.

PMID- 10085962
TI  - Nursing care for jaundice.

PMID- 10085964
TI  - The innovation game. Interview by Robert Munro.

PMID- 10085963
TI  - Practice nurses' use of evidence--based research.
AB  - Practice nurses are involved in activities related to the prevention of
      cardiovascular disease and stroke. But the degree to which they use evidence
      based practice in this area varies considerably. A Department of Health-funded
      study of 1,187 practice nurses in 11 health authorities identified significant
      links between individual and organisational factors and the use of research to
      guide practice. The study's authors discuss issues surrounding educational
      preparation, accessibility of research findings, the use of protocols and
      organisational influences.

PMID- 10085965
TI  - Donkey work.

PMID- 10085966
TI  - It's good to talk.

PMID- 10085967
TI  - Does age bring wisdom? The coming of age of managed care.

PMID- 10085968
TI  - Exploring wound care in Spain.

PMID- 10085969
TI  - MDS+ items not contained in the pressure ulcer RAP associated with pressure ulcer
      prevalence in newly institutionalized elderly.
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). The
      purpose of this study was to determine if MDS+ items not included in the pressure
      ulcer RAP correlated with pressure ulcer prevalence in newly institutionalized
      elderly. Additionally, this study examined whether the addition of nutritional
      status information to the correlated items increased association with pressure
      ulcer prevalence. Data were collected through a retrospective chart review of 990
      residents over age 65 at eight nursing homes. Pressure ulcer prevalence was
      33.2%. Nineteen of 59 non-RAP MDS+ items were correlated with pressure ulcer
      prevalence. Logistic regression determined that 10 MDS+ items predicted pressure
      ulcer prevalence in 28.88% of the subjects. Including serum albumin in the
      logistic model increased the predictability for pressure ulcer prevalence to
      36.3%. Results of this study demonstrate the strong association between nutrition
      and pressure ulcer prevalence and the need to revise the pressure ulcer RAP.

PMID- 10085970
TI  - The role of Apligraf in the treatment of venous leg ulcers.
AB  - A cultured, allogeneic, bi-layered human skin equivalent has recently become
      available to help clinicians manage difficult-to-heal venous ulcers. This skin
      equivalent has an epidermis and dermis similar to human skin. Its living
      keratinocytes and fibroblasts are from cultured cell banks derived from human
      neonatal foreskin. Because the skin equivalent is made up of viable human cells,
      it cannot be terminally sterilized. Safety concerns, which have been addressed,
      include the risk of possible transmission of infection, immunogenicity,
      immunological graft rejection, and tumor formation. However, the maternal blood
      of the neonatal donor and the master cell banks are screened for infectious
      agents. Additionally, the human skin equivalent is produced under strict aseptic
      control, with sterility continuously monitored by the Good Manufacturing
      Processes. This paper reviews the characteristics of this human skin equivalent
      and provides practice guidelines.

PMID- 10085971
TI  - Stress urinary incontinence: issues and answers for women.
AB  - Women's healthcare issues have become increasingly important. Specific healthcare
      issues, including management of high blood pressure, obesity, and menopause have
      been on the forefront for years. Today, urinary incontinence in women of all ages
      is seen as a major healthcare concern. The impetus for this increased awareness
      began in 1988 at the National Institutes of Health Consensus Conference on Adult
      Urinary Incontinence, which was followed by the publication of the Guideline for
      Adult Urinary Incontinence by the Agency for Health Care Policy and Research in
      1992. Since that time, there has been an increased focus on the problem of
      urinary incontinence. Many hope that more women will seek professional guidance
      for the evaluation and management of urinary incontinence as a result of this
      increased awareness. Healthcare professionals need to be current on the various
      options available for the management of urinary incontinence, particularly stress
      urinary incontinence, as it commonly affects women.

PMID- 10085972
TI  - The diabetic neuropathic ulcer: an overview.
AB  - The leading cause of amputation in patients with diabetes is the nonhealing foot
      wound and its complications. The effects of peripheral neuropathy, peripheral
      vascular disease, and infection often combine to facilitate ulcer development
      that can lead to gangrene and amputation. In many instances, foot ulcers and
      amputation can be prevented. The literature over the past 5 years has included
      information on the infrared thermometry in the diagnosis of infection and acute
      Charcot change. Pressure downloading has been facilitated by computerized foot
      scanning systems and the use of prefabricated pneumatic walkers as an alternative
      to the contact cast. Local wound care is enforced by repeated sharp debridement.
      Nonhealing ulcers can benefit from biologicals: platelet-derived growth factors
      and a human dermal replacement containing viable fibroblasts. The most successful
      outcomes are achieved when interdisciplinary teams are formed to provide
      coordinated care. The goal of this article is to provide healthcare professionals
      with an overview of the risks of neuropathic foot injury and to offer strategies
      for prevention, protection, and reduction of recurrences of the diabetic foot
      ulcer.

PMID- 10085973
TI  - Ostomy care: foundation for teaching and practice.
AB  - Current approaches to ostomy management evolved from the extensive experience of
      surgeons, enterostomal therapy nurses, staff nurses, patients, and manufacturers.
      Advances in surgical techniques in the 1950's led to decreased morbidity and
      mortality previously associated with ostomy surgery. With these advances, a
      corresponding demand emerged to meet the rehabilitative needs of these patients
      by providing significant physical and psychological support. The birth of
      enterostomal therapy in 1958 focused interest, energy, and resources on this
      important area of patient care. Today's tradition-based practice continues to go
      a long way in meeting the physical and psychological needs of individuals
      undergoing ostomy surgery. However, in this era of managed care, shrinking
      healthcare dollars, and standardized guidelines, care practices not derived from
      evidence or consensus may jeopardize a patient's access to appropriate
      interventions and supplies. An exhaustive review of the literature revealed a
      paucity of ostomy-related research. The effectiveness of preoperative stoma site
      selection, prevention, care, and treatment of peristomal skin problems; and pouch
      selection and wearing times revealed a wealth of empirical evidence, but little
      or no objective data supporting commonly accepted interventions. The care of
      individuals with urinary and fecal diversions is both an art and a science.
      Evidence-based practice is needed to provide a firm foundation from which the art
      of individualized patient care can flourish. Research related to pre- and
      postoperative care and rehabilitation of individuals with ostomies can only serve
      to improve education, continuity of care, reimbursement, and most importantly,
      optimize patient care.

PMID- 10085974
TI  - Care of venous leg ulcers.
AB  - For many decades, few advances occurred in the treatment of venous ulcers.
      Clinicians mainly relied on compression using gauze impregnated with zinc oxide-
      the Unna boot. During the past few years, however, much has changed in favor of
      clinicians. A variety of compression bandages are now available along with
      effective wound dressings that take advantage of moist wound healing, better
      topical agents, new systemic therapies, and living bioengineered skin. In fact,
      the problem facing clinicians today may be in deciding what treatments to use in
      addition to compression therapy, which remains the accepted standard of care for
      venous ulcers. This paper discusses advances that have occurred during the past
      several years in the understanding and treatment of venous leg ulcers, and their
      implications for clinical practice, education, and future research.

PMID- 10085975
TI  - Clinical practice guidelines: moving into the 21st century.
AB  - Clinical practice guidelines affect every aspect of healthcare. Practitioners,
      third-party payors, regulatory bodies, governments, and accrediting agencies
      increasingly use these guidelines, which are developed by a wide variety of
      organizations. The majority of guidelines are based on consensus and a
      nonsystematic literature review, but some, including those developed by the
      Agency for Health Care Policy and Research, are evidence based. Both types of
      guidelines have distinct advantages and limitations. Consensus-based guidelines
      are less time consuming to develop but may lack crucial information and result in
      a wide variety of outcomes; whereas, the type of evidence used to develop
      strength-of-evidence ratings for evidence-based guidelines may result in
      ambiguous recommendations and cause ethical concerns. Outcomes research on the
      use of guidelines and issues related to their timeliness need to be addressed.
      Studies that include a wide variety of outcome indicators and care variables and
      contributions of clinicians are needed to develop practice guidelines that are
      clinically useful and improve patient care.

PMID- 10085976
TI  - Pressure ulcer patient and wound assessment: an AHCPR clinical practice guideline
      update.
AB  - The Agency for Health Care Policy and Research (AHCPR) clinical practice
      guidelines on the treatment of pressure ulcers are based on the literature
      published before 1994. For the patient and wound assessment recommendations, a
      review of the literature from 1993 to 1998 was conducted in an effort to update
      this section of the guideline. In addition, the strength-of-evidence rating
      system used was critiqued for its narrow definitions, particularly as it pertains
      to recommendations related to assessment practices. Studies to determine the
      prospective validity of the entire guideline, as well as further research to
      assess the validity of individual recommendations, is needed.

PMID- 10085977
TI  - An update on horizontal patient support surfaces.
AB  - Horizontal patient support surfaces play an important role in the prevention and
      development of pressure ulcers. This article reviews the literature published on
      these support surfaces since the release of the Agency for Health Care Policy and
      Research (AHCPR) Clinical Practice Guideline Number 15: Treatment of Pressure
      Ulcers. The purpose of this review is twofold: One, to see if any new evidence is
      available to assist the clinician in making scientifically based decisions in the
      use of support surfaces, and two, to determine if new knowledge about support
      surfaces would change the AHCPR recommendation.

PMID- 10085978
TI  - Pressure ulcer debridement and cleansing: a review of current literature.
AB  - Optimal wound healing can only occur in a clean wound. Cleaning the wound of
      inflammatory stimuli such as devitalized tissue, reactive chemicals, and bacteria
      involves the procedures of debridement and cleansing. Debridement can be
      accomplished surgically, mechanically (wet-to-dry gauze), or chemically
      (autolysis or topical enzymes). Several recent studies are summarized that
      document the benefits of each of these techniques. Cleansing is the process of
      using fluid to remove loosely adherent foreign material. Numerous wound cleansing
      solutions and novel irrigation systems have been introduced in recent years. The
      potential benefits and harms of these products are discussed.

PMID- 10085979
TI  - The AHCPR pressure ulcer infection control recommendations revisited.
AB  - The 1994 AHCPR Pressure Ulcer Treatment Guideline had five recommendations on
      infection control topics. A review of the literature since mid-1993 when the
      evidence to support these recommendations was undertaken is reported on here. The
      author suggests that the recommendations be revisited in light of two recent
      quasi-experimental studies, but since no randomized controlled trials were found,
      the strength-of-evidence ratings should remain at C for all five recommendations.
      Infection control for chronic wound care is a complex issue and is clearly in
      need of further research. In the meantime, common-sense, reasonably prudent, do
      no-harm interventions should be considered best practice.

PMID- 10085980
TI  - Dressings and ajunctive therapies: AHCPR guidelines revisited.
AB  - The Agency for Health Care Policy and Research Pressure Ulcer Treatment
      Guidelines released in 1994 offered 11 recommendations relating to the use of
      dressings and adjunctive therapies. These recommendations were based on evidence
      gleaned from the medical literature from 1966 to mid-1993 as well as the
      accumulated expertise of a multidisciplinary advisory panel. As the
      recommendations are now 5 years old, a review of the literature published since
      1993 was undertaken in order to determine additional evidence for their continued
      validity or disapproval. The review focused on evidence at the level of
      controlled clinical trials of dressings and adjunctive therapies in the treatment
      of pressure ulcers.

PMID- 10085982
TI  - Holistic child protection.

PMID- 10085981
TI  - Bacterial colonization/infection and the surgical management of pressure ulcers.
AB  - The purpose of this paper is to review the current recommendations and guidelines
      for the care and treatment of pressure ulcers with specific reference to the
      control of infection within these wounds and surgical management. After reviewing
      the literature published between May 1993 and April 1998, it is our contention
      that no significant changes in the clinical management of this problem are
      warranted. This may signal the need for further study in this area.
      Recommendations for the optimal care of clean and infected pressure ulcers are
      included.

PMID- 10085983
TI  - A sharing, caring experience.

PMID- 10085984
TI  - Improving advocacy and partnership: reflection on a critical incident.

PMID- 10085985
TI  - Nebulisation: techniques and care.

PMID- 10085986
TI  - Assessment of growth & development.

PMID- 10085987
TI  - Diet following tonsillectomy.

PMID- 10085988
TI  - Working in harmony: the role of a musician in residence.

PMID- 10085989
TI  - Advanced practice in the US: Part One: The paediatric nurse practitioner.

PMID- 10085990
TI  - Skin cleansing and infection control in peripheral venepuncture and cannulation.

PMID- 10085991
TI  - Poster presentation: how to tell a story.

PMID- 10085992
TI  - New pediatric dosage rules: information and testing.

PMID- 10085993
TI  - The COPE program: a strategy to improve outcomes of critically ill young children
      and their parents.
AB  - Critically ill young children and their parents are subjected to multiple
      stressors during hospitalization, which may predispose them to short- and long
      term negative outcomes. Nurses who care for children who are critically ill and
      their families during and following their intensive care unit stay must be
      knowledgeable of the impact of a child's critical illness on the family and
      factors influencing adjustment to the stressful experience. Knowledge of these
      issues is essential in planning effective intervention strategies to enhance
      coping outcomes in this population. This article (a) discusses how young children
      and their parents are affected by critical illness; (b) outlines major sources of
      stress for families; (c) identifies factors influencing coping outcomes; and (d)
      describes the COPE program, a newly devised early intervention program for
      critically ill young children and their parents.

PMID- 10085994
TI  - Co-bedding of twins in the neonatal intensive care unit.
AB  - The increased incidence of multiple gestations has raised many questions
      regarding the differences in the care of twins versus singletons. The concept of
      co-bedding twins in the neonatal intensive care unit (NICU) has drawn increased
      attention in recent years. A NICU in a children's hospital in the Mid-Atlantic
      region of the United States explored the benefits and risks to this practice, and
      developed a guideline for double bunking twins. The guideline provides health
      care professionals with a safe and efficient means to arrange a physical
      environment that will simulate the environment many parents will use at home.
      Research is needed to determine the potential physical, psychologic, or
      psychosocial benefits of co-bedding multiple-gestation infants.

PMID- 10085995
TI  - The effect of music and multimodal stimulation on responses of premature infants
      in neonatal intensive care.
AB  - To assess the benefits of lullaby singing and multimodal stimulation on premature
      infants in neonatal intensive care, 40 infants in a Level III Newborn
      Intermediate Care Unit were divided into control (n = 20) and experimental (n =
      20) groups by pair matching on the basis of gender, birthweight, gestational age
      at birth and severity of medical complications. Participants met these project
      criteria: (a) corrected gestational age > 32 weeks; (b) age since birth > 10
      days; and (c) weight > 1700 g. All participants had been referred for
      developmental stimulation by the medical staff. Experimental infants received
      reciprocal, multimodal (ATVV) stimulation paired with line singing of Brahms'
      Lullaby. Stimulation was provided for 15-30 minutes, one or two times per week
      from referral to discharge. Dependent variables were (a) days to discharge, (b)
      weight gain/day, and (c) experimental infants' tolerance for stimulation. Results
      showed that music and multimodal stimulation significantly benefited females'
      days to discharge and increased weight gain/day for both males and females. Both
      male and female infants' tolerance for stimulation showed marked and steady
      increase across the stimulation intervals with females' tolerance increasing more
      rapidly than males.

PMID- 10085996
TI  - Routine meconium screening versus drug screening per physician order: detecting
      the true incidence of drug-exposed infants.
AB  - National statistics indicate that 11% of newborns are exposed to drugs of abuse
      in utero (Chasnoff, Burns, Schnoll, & Burns, 1985). From July through November of
      1993, 0.2% (1/583) of infants in our hospital screened positive for exposure to
      drugs of abuse in utero, by blood and urine screens collected per physician's
      order. During the same 4 months in 1995, 0.2% (1/574) screened positive. In
      contrast, from July through November 1994, all newborns born at our institution
      were screened for in utero drug exposure using meconium samples; approximately
      4.5% (22/493) were positive. Meconium screening of all infants, not just those
      per physician order, produced a dramatic increase in positive drug results. Of
      great concern in this study was that only two of the 22 mothers identified as
      having drug-screen positive babies during the 1994 meconium screening agreed to
      use rehabilitative services. This highlights the necessity of intervention
      through early educational programs stressing prevention.

PMID- 10085997
TI  - Evaluating children's literature as a source for patient education.
AB  - Children's literature can be used to educate patients about illness, surgery, and
      hospitalization. However, nurses must evaluate popular literature for
      developmental appropriateness and content accuracy. Developmental considerations
      for selecting appropriate children's literature as patient education material
      include cognitive abilities, language development, and children's literary
      preferences. Content accuracy is judged based on current practice. Twenty-three
      children's books addressing surgery and hospitalization were reviewed by the
      senior author. A seven-step process was utilized to determine the appropriateness
      of each piece of children's literature reviewed. Based on the review, four common
      content inaccuracies were identified: (a) the depiction of nurses and their
      roles, (b) parental visitation policies, (c) preoperative preparation
      requirements, and (d) the depiction of inpatient surgeries that are currently
      performed on an outpatient basis. Only four of the 23 books reviewed were
      recommended to prepare children for surgery in the authors' community. The
      process of reviewing a book is demonstrated using the example of Curious George
      Goes to the Hospital.

PMID- 10085998
TI  - Review and commentary: two studies regarding giving "bad news".
AB  - Informing parents of the diagnosis of a chronic illness or disability in their
      child can be a difficult task. At the same time it is critical that the informing
      is done well. Two studies examining parental reactions to the "informing
      interview" (Krahn, Hallum, & Kime, 1993; Garwick, Patterson, Bennett, & Blum,
      1995) support the conventional considerations that both parents, in a two-parent
      family, should be together when told of their child's diagnosis; parents should
      be informed early on; simple, direct language without medical jargon should be
      used; and the informing professional should be both empathetic and supportive of
      parental emotional expression. These studies raise additional considerations
      including the importance of meeting with parents in person, informing parents in
      a private setting, pointing out the child's strengths as well as limitations, and
      individualizing both the communication style and information shared. Cross
      cultural considerations, while not addressed in either of these studies, require
      attention to language interpretation, meaning assigned to the diagnosis, and
      potentially differing treatment preferences. In all cases, nurses should evaluate
      the effectiveness of the informing interview in relation to the family's
      affective and information needs. Each of these considerations should be part of
      the process of an informing interview.

PMID- 10085999
TI  - Developing a pediatric diabetes critical pathway.

PMID- 10086000
TI  - "Waiting in Araf" research without consent: a Turkish mother's experience.
AB  - In this article, a nurse author from Turkey relates the anxiety and struggle that
      she experienced with the birth of her first baby when, for unknown reasons, the
      baby experienced acute rectal bleeding after birth. Unsatisfactory doctor-patient
      relations, abolishment of patient rights, suspicion of research without
      permission, and clinical iatrogenesis are discussed. The mother describes the 10
      days she spent with her child in the hospital as "waiting in Araf." According to
      Middle Eastern culture, "Araf" is defined in the Koran as a place between Eden
      and Hell where people who have sinned are required to wait. Though anticipating
      acceptance into Eden, they wait with fear as they watch Hell on one side, and
      with hope while watching the happiness of Eden on the other side. The author's
      story depicts such an experience.

PMID- 10086001
TI  - Commentary on "Waiting in Araf". Informed consent: issues and regulations.
AB  - Children have the right to safety and appropriate consideration of their
      physical, emotional, and psychological needs in regards to treatment or research
      decisions. Parents have an equal right to be honored in their parenthood and
      respected for what they would want as the best thing for their child as a member
      of the family. When children are mature enough, they should be offered the
      opportunity of assenting or dissenting to research participation. Until such
      time, parents may make what they feel to be the best decisions. If a nurse feels
      that these principles are being violated, he or she should attempt to seek
      further clarification. In order to obtain information about an ongoing research
      project, it would be appropriate to contact the IRB or a member of the hospital
      ethics committee. In most cases, a satisfactory explanation will be found. In the
      rare case that patient's rights are truly being violated, the American Nurses
      Association Code of Ethics requires that nurses report incompetent, unethical, or
      illegal practices (ANA, 1994). Nurses who "whistle-blow" may or may not be
      protected against retaliation. Some states in the U.S. have developed laws that
      prohibit the discharge of an employee who reports unethical practices. One might
      expect that in some countries a nurse might not only endanger her position for
      such reporting but endanger his or her life as well. Ulusoy reports on research
      done on children without knowledge or consent of parents. Although this case took
      place long ago, it is certain that there are still countries in which informed
      consent is undeveloped and such practices continue. Nurses in developed countries
      with established consent policies can be hopeful that such activity is no longer
      seen here. As international collaboration in nursing research grows, nurses in
      developed nations can work to provide educational opportunities regarding the
      consent process for colleagues across the globe.

PMID- 10086002
TI  - International adoption: a primer for pediatric nurses.
AB  - Immigrant visas issued to orphans entering the United States (a proxy measure for
      international adoptions) totaled 13,620 in 1997, more than double the amount in
      1992. As international adoption numbers rise, pediatric nurses encounter more
      adopted children and adoptive families. Among the many adoption-related issues
      confronting pediatric health care providers, the one most frequently voiced is:
      "Should we do or look for anything differently in adopted children? And, if so,
      what?" To address this issue, a three-fold approach is suggested: (a) recognize
      the physical conditions and medical problems prevalent in the international
      countries with high adoption rates; (b) identify the unique adoption-related
      tasks encountered by children according to their current developmental stage; and
      (c) determine recommendations for providers, parents, and children to
      successfully address or cope with these adoption-related tasks and conditions.

PMID- 10086003
TI  - Pediatric management problems. Hirschsprung's disease.

PMID- 10086004
TI  - University affiliated programs: a network of nursing resources for children and
      youth with disabilities.

PMID- 10086005
TI  - Do not resuscitate (DNR): state policies for at-home and in-school.

PMID- 10086006
TI  - Pediatric nursing Humanitarian Award recipient offers hope to children with AIDS.

PMID- 10086007
TI  - Court upholds license suspension for forged Rxs.

PMID- 10086008
TI  - Male charge nurse sexually assaults nurse.

PMID- 10086009
TI  - OH: aged agitated pt. with dementia falls: expert testimony-no deviation from
      standards.

PMID- 10086010
TI  - LA: cardiac post-op patient falls twice: suit brought vs. hospital physicians &
      nurses.

PMID- 10086012
TI  - Back to the future: the year 2000 problem.

PMID- 10086011
TI  - SIDS--Discontinuance of CPR results in suit.

PMID- 10086013
TI  - Ethics on the job: a survey. Staffing issues.
AB  - In this fourth installment of our series on ethical issues, we'll examine how
      patient care is affected when there just aren't enough nurses to go around. We'll
      look at how nurses are coping with that situation, and how UAPs now factor into
      the mix.

PMID- 10086014
TI  - Strangulation.
AB  - This final installment in our series focuses on survivors of hangings and other
      forms of strangulation. We'll cover neck anatomy, the four types of
      strangulation, and the interventions that can keep patients' injuries from
      turning deadly.

PMID- 10086015
TI  - Love songs.
AB  - The demands of medical technology, of tubes and meds, often overshadow the caring
      and giving that are the very core of nursing. Patients like Alice--and her
      husband--help reaffirm the values that led me into the profession.

PMID- 10086016
TI  - What's wrong with this patient?

PMID- 10086017
TI  - A TEAM approach to NICU care.
AB  - The NICU can be a very stressful place not only for the infants who need
      intensive care, but also for their parents. By implementing family-centered care
      using the TEAM model described here, nurses can make baby's stay less upsetting,
      promote bonding between parents and child, and help improve postpartum care.

PMID- 10086018
TI  - G-tube site care: a practical guide.
AB  - Effective care of your patient's gastrostomy site is key to her recovery--even
      after she's been discharged. Here we'll zero in on the prevention and treatment
      of skin problems and tube dislodgement, and review which anchoring device best
      suits your particular patient's needs.

PMID- 10086019
TI  - Tai chi: a martial art turns therapeutic.

PMID- 10086020
TI  - When information must be revealed.

PMID- 10086021
TI  - When your patient experiences "too much" pain.

PMID- 10086022
TI  - Warning signs of elder abuse.

PMID- 10086023
TI  - Geriatrics photo quiz. Chronic constrictive pericarditis.

PMID- 10086024
TI  - Yellow lesions with a central depression. Location of the eruption provides clue
      to diagnosis.

PMID- 10086025
TI  - Delirium: making the diagnosis, improving the prognosis.
AB  - Delirium is a common development in at-risk older patients hospitalized for acute
      illness or postoperative care. Although delirium's risk factors are well
      documented, less is known about its pathophysiology and long-term prognosis or
      about the relationship between delirium, dementia, and depression. Evaluation and
      management of delirium is a medical emergency. Diagnostic tools include the
      Confusion Assessment Method rating scale, patient history from capable
      informants, and physical/mental examinations. Management consists of prevention,
      treatment of underlying causes or associated factors, supportive care, and
      pharmacologic intervention (as indicated). Studies that have looked at the
      reversibility of delirium suggest that patients often are slow to recover their
      previous level of function.

PMID- 10086026
TI  - Leg ulcers: a common problem with sometimes uncommon etiologies.
AB  - In the U.S., leg ulcers present a significant clinical problem, occurring at a
      rate of approximately 600,000 new cases per year. In most cases, the cause of
      ulceration is venous or arterial in nature. One uncommon but significant cause of
      leg ulcers is sqaumous cell carcinoma (SCC). Although the incidence of SCC is
      higher in white than black populations, blacks with SCC typically exhibit
      involvement of areas of the skin that are not chronically sun-exposed, especially
      the lower extremeties. Predisposing factors include burn scars, chronic infection
      or ulceration, and chronic discoid lupus erythematosus. Leg ulcers of atypical
      presentation or those that fail to heal should alert the clinician to consider
      uncommon etiologies.

PMID- 10086027
TI  - Cardiovascular disease: tomorrow is the reason for today's therapeutics. An
      interview with Jerome D. Chen.
AB  - The prevalence and magnitude of cardiovascular disease in the United States make
      it the leading cause of mortality, far surpassing deaths from all cancers. More
      than 900,000 Americans die each year from cardiovascular causes, including
      stroke, hypertension, congestive heart failure, atherosclerosis, and congenital
      heart defects, according to American Heart Association estimates. Coronary heart
      disease alone accounts for 50% of all cardiovascular deaths. A host of agents
      designed to help manage cardiovascular disorders and related conditions (eg,
      hypertension, diabetes, and hypercholesterolemia) are available to physicians who
      treat patients at high risk. In this interview, Jerome D. Cohen, MD, explains why
      more aggressive use of these drug treatments today could significantly improve
      older patients' quality of life and reduce the risk of a disabling or fatal
      cardiovascular event in the next millennium.

PMID- 10086028
TI  - Magnesium deficiency and dizziness: a case of electrolyte imbalance.

PMID- 10086029
TI  - How good could it get? Improving clinical practice and patient outcomes.

PMID- 10086030
TI  - The costs of being first. Can you afford to be a technology pioneer?

PMID- 10086031
TI  - What is a complete physical?

PMID- 10086032
TI  - Sorting through the hype about RDAs.

PMID- 10086033
TI  - How to manage primary pulmonary hypertension. Giving hope to patients with a life
      threatening illness.
AB  - Primary pulmonary hypertension presents a challenge to practicing physicians, in
      both diagnosis and management. Exposure to anorexigens and complaints of dyspnea
      and fatigue should prompt careful physical examination and Doppler
      echocardiography to assess patients for pulmonary hypertension. The burden on
      office practitioners is heavy, considering how often fatigue and dyspnea are
      reported, but the key is recognizing when these findings are out of proportion to
      the patient's well appearance. The discovery of epoprostenol therapy has
      revolutionized the approach to primary pulmonary hypertension. It has markedly
      improved quality of life and extended survival in patients with the condition,
      and it has changed the physician's role from providing emotional support to dying
      patients to providing management of a chronic disease.

PMID- 10086034
TI  - How to help patients with restless legs syndrome. Discerning the indescribable
      and relaxing the restless.
AB  - Restless legs syndrome is a common, potentially disabling condition that affects
      about 10% to 15% of the general population and yet is often unrecognized and
      misdiagnosed. It is mainly diagnosed clinically and only rarely requires
      polysomnography. The condition is usually primary and treatable. First, however,
      secondary causes should be sought, especially iron deficiency and peripheral
      neuropathy, because when the source is an accompanying factor or condition, the
      syndrome may be curable. The most effective drugs are dopaminergic agents,
      clonazepam, opioids, gabapentin, and clonidine. Additional agents are available
      that may be beneficial as add-on or alternative therapy.

PMID- 10086035
TI  - Steroid-induced osteoporosis. Are your asthmatic patients at risk?
AB  - Asthmatic patients who rely on long-term, high-dose corticosteroid therapy are at
      increased risk for osteoporosis. The use of low-dose inhaled corticosteroids may
      be safe enough not to require special assessment of bone loss or preventive
      measures. However, evidence is lacking on the risks of long-term use of higher
      doses. Regardless of dose, all patients given long-term systemic corticosteroids
      should be carefully examined and, if necessary, treated for bone loss.

PMID- 10086036
TI  - Scope and consequences of peptic ulcer disease. How important is asymptomatic
      Helicobacter pylori infection?
AB  - H pylori infection is so common as to seem ubiquitous in many areas of the world.
      Transmission is believed to be primarily person to person. The pathogen
      invariably damages the gastric mucosa, resulting in both structural and
      functional abnormalities. It causes histologic gastritis and is critical in the
      pathogenesis of the gastritis-associated diseases, namely, gastric ulcer,
      duodenal ulcer, gastric adenocarcinoma, and primary gastric lymphoma. Elimination
      of the infection results in healing of gastritis and cure of peptic ulcer
      disease.

PMID- 10086037
TI  - Recognizing peptic ulcer disease. Keys to clinical and laboratory diagnosis.
AB  - An algorithmic approach to evaluation of dyspepsia or abdominal discomfort begins
      with differentiation between peptic ulcer disease and gastroesophageal reflux
      disease as well as recognition of alarm signs and symptoms for gastric cancer,
      which are indications for early endoscopy. In the absence of alarm symptoms, most
      patients should undergo noninvasive testing for H pylori infection with a
      serologic, urea breath, or stool antigen test. Factors to consider in selection
      of appropriate testing include reliability, specificity, sensitivity, cost, and
      local access and expertise. As a general rule, physicians should choose a test
      that has the best accuracy for the level of testing expertise available. The
      basic principle underlying testing for H pylori is that patients should not
      undergo testing unless the physician is willing to treat on the basis of a
      positive test result. In patients who receive treatment, confirmation of cure is
      important for preventing further morbidity and reducing risk of transmission of
      infection.

PMID- 10086038
TI  - Practical advice on eradicating Helicobacter pylori infection.
AB  - Peptic ulcer disease associated with H pylori infection is curable. The important
      factors in selecting therapy are efficacy of eradication, prevention of
      resistance, avoidance or minimization of adverse effects, patient compliance, and
      cost. The most effective regimens include a bismuth preparation or antisecretory
      drug (proton pump inhibitor or H2 receptor antagonist) plus two antibiotics
      administered for 14 days. Dual-drug therapies are not recommended. Triple-drug
      regimens are more likely to eradicate H pylori and less likely to generate
      resistant strains among surviving organisms. In general, cure of the infection
      should be confirmed 4 weeks after completion of the treatment. Antibiotic
      resistance is an important consideration in choosing therapy, and patients should
      be taught the importance of compliance. When treatment fails, antibiotic
      combinations should not be repeated. Considerations for anti-H pylori treatment
      in a managed care environment mirror those for good medical practice in general,
      with special attention to stringent cost-control or outcomes-driven measures.

PMID- 10086039
TI  - Skin commotion from repetitive devotion. Prayer callus.

PMID- 10086040
TI  - Lower extremity compartment syndrome. When to suspect acute or chronic pressure
      buildup.
AB  - Acute compartment syndrome is a surgical emergency. A high index of suspicion is
      needed in cases of severe contusion, especially if patient complaints seem to
      outweigh physical findings. Acute surgical fasciotomy is an effective treatment
      and should be carried out expeditiously if compartment pressures are elevated
      over 70 mm Hg in order to avoid complications such as chronic disability due to
      contractures or rhabdomyolysis with acute renal failure. Chronic exertional
      compartment syndrome most often occurs in the anterior or the lateral
      compartment. Patients have only exercise-related symptoms and recover quickly
      after resting from the inciting activity. Diagnosis is difficult, but the
      anterior compartment pressure may be checked fairly readily with a handheld
      pressure catheter. Deep posterior compartment problems are harder to check
      because of the difficulty in reaching this area. Thallium stress testing appears
      promising for diagnosing both anterior and posterior problems and may augment, or
      even replace, the catheter measurement in the deep posterior and perhaps even the
      anterior compartment. Thallium stress testing is noninvasive and may be a more
      physiologic measurement. Fasciotomy may be indicated if conservative treatment
      lacks efficacy. For unknown reasons, the deep posterior compartment does not
      respond as quickly, or as well, to fasciotomy as the anterior compartment.

PMID- 10086041
TI  - Common allergic and allergic-like reactions to medications. When the cure becomes
      the curse.
AB  - Adverse drug events are the leading cause of medical injury in hospitalized
      patients in the United States. The number of persons affected is roughly four
      times the total number killed in automobile accidents every year. The good news
      is that most adverse drug events are preventable through careful and thorough
      management. In the spirit of "First, do no harm," the authors of this article
      discuss common anaphylactic and allergic-like reactions to medications and what
      you can do to minimize the risks.

PMID- 10086042
TI  - Helping your patients beat cocaine addiction. The four dimensions of treatment.
AB  - Despite public health efforts aimed at curbing the steady increase of drug abuse
      in this country, many patients continue to require treatment for cocaine
      addiction. A comprehensive treatment approach requires integration of
      pharmacologic, psychological, social, and spiritual dimensions, although research
      is needed to demonstrate the efficacy of such an approach in maintaining
      abstinence. Primary care physicians' assessment and treatment of their cocaine
      addicted patients is a critical initial step on the way to specialized
      psychiatric and/or other specialized care for addiction and, hopefully, to
      sustained recovery.

PMID- 10086043
TI  - A practical workup for eosinophilia. You can investigate the most likely causes
      right in your office.
AB  - The vast majority of cases of eosinophilia in North America are caused by
      allergic processes. In individual cases, a short differential diagnosis of the
      most likely causes can be formulated on the basis of the absolute eosinophil
      count. The extensive laboratory workup previously recommended by some authorities
      is probably not justified unless detailed history taking and physical examination
      indicate a need for specific investigations. Although the possibility of missing
      an occult neoplasm has been used to justify extensive investigation, this is
      usually not necessary because most tumor-associated eosinophilia is accompanied
      by widely metastatic disease. History taking should emphasize the possibility of
      drug-induced or helminth-associated eosinophilia. If the history indicates
      travel, dietary, or other exposure risks, stool examination for ova and parasites
      is worthwhile. If a possible allergic cause is suspected, testing for evidence of
      atopy may be performed concomitantly with testing for parasitic infection. A
      follow-up white blood cell count with differential is recommended to ascertain
      whether eosinophilia has resolved. When an absolute eosinophil count of more than
      1.5 x 10(9)/L persists for longer than 6 months, idiopathic hypereosinophilic
      syndrome must be ruled out.

PMID- 10086044
TI  - Is 'routine' laboratory testing a thing of the past? Current recommendations
      regarding screening.
AB  - A 55-year-old man comes to you for a routine physical examination. He is a
      nonsmoker who takes no medications and has no signs of acute or chronic disease,
      and he has not seen a doctor in years. What blood work should you order for this
      patient? The authors of this article help you answer this question in light of
      recent advances in technology, restrictions in healthcare reimbursement, and
      increased sophistication in cost-benefit analysis for laboratory testing.

PMID- 10086045
TI  - A palpable clue to vasculitis.
AB  - A 57-year-old woman presented with a rash on her legs that had recurred several
      times over the last 2 weeks. Initial treatment had consisted of prednisone, 30
      mg/day, for 5 days, but the rash had recurred when therapy was discontinued.
      Laboratory findings at that time revealed an elevated antistreptolysin O titer,
      but a complete blood cell (CBC) count, electrolyte levels, erythrocyte
      sedimentation rate (ESR), and complement fixation test all were normal. The
      patient was subsequently given amoxicillin, which she discontinued after a few
      days when the rash worsened. Findings on physical examination were normal except
      for a palpable purpuric rash on the lower legs (figure 1). A 4-mm punch biopsy
      was performed, and histopathologic examination confirmed a diagnosis of
      leukocytoclastic vasculitis. The patient was given prednisone, 60 mg/day orally,
      tapered over 2 weeks. Erythromycin was also prescribed for the possible
      persistence of a streptococcal carrier state. The rash cleared within 2 to 3
      weeks, with no recurrence during the following year.

PMID- 10086046
TI  - New treatment for peptic ulcer disease.
AB  - The news for America's 25 million ulcer sufferers is good. It's usually not
      lifestyle that causes that gnawing pain. Most likely it's a bacterial infection.
      And the infection can be treated and permanently eliminated in most people. All
      it usually takes is 2 weeks of treatment with a combination of antibiotics and a
      drug that blocks acid production in the stomach.

PMID- 10086047
TI  - Penile reconstruction, phallic construction, and urethral reconstruction.
AB  - Penile reconstruction, phallic construction, and urethral reconstruction require
      tissue transfer in the majority of cases. This article discusses the techniques
      of tissue transfer and presents illustrative cases of penile reconstruction,
      total phallic construction, and urethral reconstruction. The modified forearm
      flaps for penile reconstruction, the ulnar forearm flap as used for total phallic
      construction, and the dartos fascial flap and penile skin islands for urethral
      reconstruction are illustrated. Graft onlay techniques also are shown.

PMID- 10086048
TI  - Current trends in hypospadias repair.
AB  - There is no single, universally applicable technique for hypospadias repair.
      Command of a technically straightforward repair with few complications and proven
      success and versatility in a reasonable range of hypospadias defects are desired
      goals. Several well-established techniques exist for the repair of all
      hypospadias defects. The Snodgrass tubularized incised plate urethroplasty, a
      recent contribution with exemplary early results, has become a popular technique
      for primary and preoperative repair of middle and anterior hypospadias. Other
      innovative modifications, and technical advances, such as the use of laser and
      tissue solder, continue to emerge. With time, these may herald improvements to
      even the most basic of sound principles involved in all hypospadias repair.

PMID- 10086049
TI  - Vaginal reconstruction.
AB  - Absence of the vagina presents a challenging problem for the reconstructive
      urologist. This article reviews the pertinent diagnostic and pretreatment
      considerations and the surgical options, in particular, bowel vaginoplasty, for
      these patients.

PMID- 10086050
TI  - Reconstructive surgery for trauma of the lower urinary tract.
AB  - Blunt external trauma is the most common cause of injuries of the lower urinary
      tract. Minor injuries often heal uneventfully with catheter drainage. Penetrating
      traumas are best treated with primary repair. Delayed reconstruction of urethral
      disruption injuries is safe and effective in the majority of cases, but immediate
      realignment is an attractive, minimally invasive alternative. Pelvic MR imaging
      and urethral ultrasound are important ancillary staging studies for evaluating
      patients who require complex urethral reconstruction.

PMID- 10086051
TI  - Reconstructive surgery for urinary incontinence.
AB  - The clinical urologist often is faced with the referral of a patient with urinary
      incontinence refractory to conservative measures. Given the broad spectrum of
      causes of urinary incontinence, the clinician must base evaluation and
      therapeutic management on current principles of urinary tract pathophysiology.
      This article organizes the pertinent diagnostic considerations that must be
      addressed in guiding the clinician to the appropriate surgical treatment option.

PMID- 10086052
TI  - New advances in injectable therapies for the treatment of incontinence and
      vesicoureteral reflux.
AB  - Clinical experience over the last two decades has demonstrated that the
      endoscopic correction of primary vesicoureteral reflux and urinary incontinence
      caused by intrinsic sphincteric dysfunction is both possible and effective. The
      ideal material for use in these regards has yet to be developed. As a result,
      there has been a continuing research effort directed towards the development of
      new injectable substances. Nonautologous substances, such as Teflon, collagen,
      and Deflux, and autologous substances such as fat, chondrocytes and muscle, have
      been used either clinically or are under investigation. Although the ideal
      substance has yet to be determined, many of the substances currently under
      development appear promising. The use of a particular substance may best be
      determined by the clinical circumstance involving each individual patient.

PMID- 10086053
TI  - Complete primary closure of bladder exstrophy. Epispadias and bladder exstrophy
      repair.
AB  - Bladder exstrophy remains one of the most challenging problems in pediatric
      urology. Recent efforts have focused on primary reconstruction rather than
      urinary diversion to treat exstrophy. Complete primary closure appears to offer
      improved continence and decreases the number of surgical procedures required to
      treat exstrophy.

PMID- 10086054
TI  - Bladder augmentation. Options, outcomes, future.
AB  - Remarkable progress has been made in lower urinary tract reconstruction in
      children. Nowhere is this more valuable than in augmentation cystoplasty, where
      there are several available options. This article discusses the current
      techniques and the benefits and limitations of these procedures. A section on
      tissue regeneration techniques and the author's current recommendations are
      included.

PMID- 10086055
TI  - Continent urinary diversion.
AB  - Continent urinary diversion has evolved from an investigational method of urinary
      tract reconstruction to an accepted, and in many instances preferred, option for
      men and women facing radical cystectomy. Over the last 15 years, we have learned
      much about the different procedures, their durability, and their success rates.
      This article reports on the procedures that the authors believe are associated
      with the highest success rates and the lowest complication rates. At this time,
      continent diversion should be offered to all appropriate candidates, and these
      procedures should be considered a part of the standard urologic armamentarium.

PMID- 10086056
TI  - Orthotopic ileocolic neobladder reconstruction following radical cystectomy:
      history, technique and results of the Johns Hopkins experience, 1986-1998.
AB  - Reconstruction of the lower urinary tract using intestinal segments has become a
      standard component of the treatment of patients with bladder cancer. A variety of
      intestinal segments can be successfully used for this purpose. Between 1986 and
      1998, the authors have used a composite ileocolic segment for neobladder
      reconstruction in patients desiring orthotopic reconstruction of the lower
      urinary tract. The early and late complication rates are 11% and 30%,
      respectively. Forty-five percent of men are potent postoperatively. Seventy-six
      percent of patients are continent both day and night. Three percent of our
      patients experience nocturnal enuresis, and 15% perform clean intermittent
      catheterization. Bothersome daytime stress urinary incontinence occurs in 3% of
      patients evaluated for this report. Although no contemporary studies demonstrate
      the superiority of a particular bowel segment for lower urinary tract
      reconstruction, the authors' long-term experience with the ileocolic neobladder
      suggests that this composite segment provides excellent results for lower urinary
      tract reconstruction after radical cystectomy.

PMID- 10086057
TI  - Future perspectives in reconstructive surgery using tissue engineering.
AB  - Whenever there is a lack of native urologic tissue, reconstruction usually is
      performed with native nonurologic tissues, such as gastrointestinal segments,
      skin, or mucosa from multiple body sites. The use of native nonurologic tissues
      in the genitourinary tract is associated with adverse effects. Tissue engineering
      efforts currently are underway for almost every type of tissue and organ within
      the urinary system including bladder, ureter, urethra, and genitalia. Most of the
      efforts expended to engineer genitourinary tissues have occurred within the last
      decade. Tissue engineering techniques require a cell culture facility designed
      for human application. Personnel who have mastered the techniques of cell
      harvest, culture and expansion, and polymer design are essential for the
      successful application of this technology. The first human application of cell
      based tissue engineering technology for urologic applications recently occurred
      with the injection of autologous cells for the correction of vesicoureteral
      reflux in children and urinary incontinence in adults. Trials involving bladder
      replacement using tissue engineering techniques currently are being arranged.
      Recent progress suggests that engineered urologic tissues may have clinical
      applicability.

PMID- 10086058
TI  - Lower ureteral reconstruction.
AB  - Lower ureteral reconstruction is commonly performed in instances of congenital
      anomalies and ureteral injury. Keys to a successful outcome are an understanding
      of ureteral anatomy, familiarity with the principles of tissue handling, and the
      knowledge of various techniques of repair. This article presents some important
      and useful reconstructive techniques that can be considered in the management of
      patients with congenital anomaly or lower ureteral injury.

PMID- 10086059
TI  - Upper ureteral reconstructive surgery.
AB  - Upper ureteral reconstructive surgery encompasses a wide variety of procedures
      directed at the correction of abnormal processes and structural defects in the
      proximal ureter. Although some of these techniques have strict indications for
      specific causes, technical innovations have led to development of numerous
      alternatives in upper ureteral reconstructive surgery. These innovations provide
      the practicing urologist with various options from which to choose for the
      management of upper ureteral disease.

PMID- 10086060
TI  - Reconstructive surgery for trauma of the upper urinary tract.
AB  - In general, the authors surgically reconstruct kidneys with major parenchymal
      lacerations or vascular injuries, particularly when intra-abdominal injuries are
      present. Regardless of the mechanism of injury, roughly 90% of explored kidneys
      can be successfully reconstructed. Adherence to the principles of early proximal
      vascular control, debridement of devitalized tissue, hemostasis, closure of the
      collecting system, and coverage of the defect maximizes the salvage of renal
      function while minimizing potential complications. As to ureteral injuries, a
      high index of suspicion is crucial, especially because urinalysis and imaging
      studies can be unreliable. The majority of ureteral injuries can be successfully
      reconstructed by primary repair, ureteroureterostomy, or ureteral
      reimplantations, with or without a psoas bladder hitch.

PMID- 10086061
TI  - Complex renal reconstruction.
AB  - This article provides a complete review of current renal reconstructive
      techniques. The techniques described include partial nephrectomy, intrasinusal
      surgery, anatrophic nephrolithotomy, nonvascular bench procedures with
      autotransplantation, and allograft partial nephrectomy in renal transplantation.
      A detailed discussion on renovascular and collecting system anatomy and current
      indications for these procedures is presented.

PMID- 10086062
TI  - Vascular reconstruction in urology.
AB  - Vascular reconstructive surgery in urology includes techniques of
      revascularization of the renal artery for renovascular hypertension or ischemic
      nephropathy in situ or extracorporeal renal artery reconstruction. The
      indications for aortorenal bypass, extra-anatomic bypass, or simultaneous aortic
      substitution and renal revascularization are based on the cause, location, and
      extent of the vascular lesion. Techniques of bench surgery mainly depend on
      location of the renal artery disease and availability of autologous graft
      material.

PMID- 10086063
TI  - Current and future modalities for functional renal replacement.
AB  - Approximately 310,000 Americans suffer from end-stage renal disease, with more
      than 70,000 new cases reported each year. Advances in immunosuppressive therapy
      for transplanted patients, in addition to the refined care of patients who are
      dependent on dialysis, have led to an improved survival for patients with renal
      failure. Structural, molecular, and pharmacologic developments continue to
      enhance the efficacy and safety of dialysis in the future. In addition,
      progressive improvements in the past 2 decades in organ transplantation, a
      greater insight into the immunobiology of graft rejection, and better surgical
      and medical management have resulted in improved outcomes. Although renal
      xenotransplantation is still in its early stages of development, additional
      research is leading this technology forward. Recent successes in harvesting and
      expanding renal cells in vitro and the development of biologically active
      synthetic materials allow for the creation of three-dimensional functioning renal
      units, which, in the future, may be applied ex vivo or in vivo for partial or
      full replacement of kidney function.

PMID- 10086064
TI  - Laparoscopic live donor nephrectomy.
AB  - Live donor renal transplantation has many advantages including greater graft and
      patient survival, shorter waiting periods, improved human leukocyte antigen
      matching, and less cold ischemia. Until recently, disincentives from the
      operation, such as prolonged hospitalization, postoperative pain, and significant
      convalescence, have deterred live donor renal transplantation. This article
      describes the technique of laparoscopic live donor nephrectomy and briefly
      reports the results. The procedure has resulted in improved postoperative
      recovery and shorter convalescence, with no effect on recipient renal function.

PMID- 10086065
TI  - Growth factors in preimplantation development: role of insulin and insulin-like
      growth factors.
AB  - In vitro studies of preimplantation embryos from a number of mammalian species
      have shown that the oviduct and uterus contain growth factors that stimulate
      cellular proliferation and differentiation of preimplantation embryos. The
      mammalian preimplantation embryo was first viewed as an autonomous entity, due to
      the ease with which mouse embryos could be cultured from the two-cell stage on to
      the blastocyst. This view changed following studies in other species, notably
      domestic animals, which revealed the presence of 'blocks' to development, when
      embryos were cultured in vitro. Another line of evidence leading to the view that
      the maternal environment is crucial for optimal development, was the finding that
      embryos cultured in vitro lag developmentally behind their in vivo counterparts.
      This developmental retardation could be ameliorated when washings from the
      reproductive tract or specific growth factors were added to the media. The
      expression of genes for growth factors and their receptors is regulated in a
      tissue-specific manner as well as temporally and spatially during mammalian
      development. In this review, information regarding the expression and role of
      polypeptide growth factors of the insulin family during preimplantation mammalian
      development is summarized.

PMID- 10086066
TI  - Genetic risk in natural and medically assisted procreation.
AB  - Current in vitro fertilization techniques (IVF) including intracytoplasmic sperm
      injection (ICSI), microepididymal sperm aspiration (MESA) or testicular sperm
      extraction (TESE) clearly prevent any spontaneous choice of ova or spermatozoa.
      According to the widely admitted concept of gamete selection, pregnancies
      following IVF, when compared to natural fertilization, could therefore present a
      higher risk of genetic anomalies. However, no increased fetal or newborn
      abnormalities are noticed with IVF, except perhaps for sex chromosome
      aneuploidies. Data from the literature support the view that the uterus is,
      indeed, the organ where selection mechanisms occur (when they do so), as
      suggested by Carr in 1971. This selection concerns mainly autosome imbalances;
      unbalanced conceptuses are aborted. Sex chromosome aneuploidies, apparently, are
      less prone to natural abortion, but their higher rate of occurrence, as reported
      in a few series of studies, does not seem to be associated with the IVF
      procedures.

PMID- 10086067
TI  - Glucose transporter (Glut1, Glut3) mRNA in human placenta of diabetic and non
      diabetic pregnancies.
AB  - Transport of glucose into the cell is catalyzed by glucose transporters (Glut).
      Glut1 and Glut3 are expressed at various levels in many human tissues, including
      the placenta. It has been reported that ambient glucose can affect both glucose
      transport activity and expression of the Glut genes, and protein. To date, very
      few studies concerning Glut in the placenta have been published, and studies in
      vivo in human diabetic pregnancy are lacking. We therefore investigated placental
      Glut1 and Glut3 mRNA by Northern blot analysis in ten diabetic (five insulin
      dependent diabetes mellitus (IDDM), two non-insulin dependent diabetes mellitus
      (NIDDM) and three gestational diabetes mellitus (GDM)) and nine non-diabetic
      women. The quantitative results of specific mRNA/beta-actin ratios were expressed
      as arbitrary units. The results were evaluated according to metabolic and
      clinical findings. Glut1 and Glut3 mRNA values in diabetic and non-diabetic
      pregnant women were similar. The metabolic environment seems to affect the Glut3
      mRNA levels in IDDM pregnant women but not the control women. In addition, Glut3
      mRNA decreased in late pregnancy in the diabetic but not in the control women.
      Moreover, Glut1 mRNA levels were correlated with maternal age in the diabetic as
      well as in the control women (significantly). Finally, an inverse correlation was
      found between Glut1 mRNA levels and placental weight (in both diabetic and non
      diabetic women). These results, although preliminary, shed some light on the
      function of these glucose transporters in normal as well as in diabetic
      pregnancies and prompt us to carry out a further investigation to better
      elucidate fetomaternal metabolic correlation at the placental level.

PMID- 10086068
TI  - 11 beta-Hydroxysteroid dehydrogenase enzyme activity in granulosa cells derived
      from ovarian follicles of in vitro fertilization patients.
AB  - 11 beta-Hydroxysteroid dehydrogenase (HSD) activity was measured in freshly
      frozen granulosa cells isolated from follicles of twenty-one infertility patients
      undergoing in vitro fertilization-embryo transfer (IVF-ET). A total of 213
      follicles were analyzed for 11 beta-HSD activity. Both nicotinamide-adenine
      dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP)
      dependent 11 beta-dehydrogenase activities were measured in granulosa cells. The
      activity in reductive direction (11-oxoreductase activity) was not measurable
      either with NADH or NADPH as cofactors. NAD- and NADP-dependent dehydrogenase
      activities are in comparable levels at 100 nmol/l and 1 mumol/l corticosteroid
      concentrations. For comparing enzyme activities of individual follicles,
      significant enzyme activity was considered to be a level of > 2 nmol/l/min/mg.
      41.3% of the follicles demonstrated enzyme activity, 58.7% did not. The mean 11
      beta-dehydrogenase (11 beta-DH) activity was calculated for each patient. Those
      patients with levels > 2 nmol/l/min/mg were considered enzyme positive; those
      with mean levels < 2 nmol/l/min/mg were considered negative. No significant
      association was noted between follicle size, oocyte maturity or fertilization
      rates and 11 beta-DH activity. This study noted the presence of 11 beta-DH
      activity in granulosa cells, however, no association with oocyte maturity and
      fertilization was found.

PMID- 10086069
TI  - Expression and production of interleukin-10 by human trophoblast: relationship to
      pregnancy immunotolerance.
AB  - Interleukin-10 (IL-10) is a T-helper type-2 (Th2) cytokine noted for its ability
      to suppress cytokine synthesis by T-helper type-1 (Th1) cells. IL-10 may play a
      role in pregnancy immunotolerance through the establishment of a Th2 cytokine
      bias at the maternal-fetal interface. This study examines the expression and
      production of IL-10 by normal and malignant human trophoblast. Term placental
      biopsies, cloned choriocarcinoma cell lines and isolated human trophoblast were
      utilized for the study of IL-10 expression. Choriocarcinoma cells (BeWo, JEG-3,
      JAR) were maintained in T-flask culture until confluence and then harvested by
      enzymatic dispersion. Purified term trophoblast were obtained by sequential
      trypsin/DNAse digests and CD9 immunoaffinity chromatography. Amplified IL-10 mRNA
      was detected by a reverse transcriptase polymerase chain reaction (RTPCR)
      technique. BeWo cells were maintained in artificial capillary culture (ACC) and
      conditioned media assayed for IL-10. Granulocyte macrophage-colony stimulating
      factor (GM-CSF; 1.0, 10.0 and 100.0 ng/ml) was added to the BeWo cultures to
      examine its effects on trophoblast IL-10 production. IL-10 determinations were
      performed using a human ELISA system. IL-10 mRNA was detected in each trophoblast
      cell type examined with the exception of the JEG-3 choriocarcinoma cell line. IL
      10 protein was also detected (range 6-22 pg/ml) in BeWo media on days 8 to 11 of
      culture. When serum was reduced in the culture media, IL-10 levels fell below the
      sensitivity of the assay (5 pg/ml). Subsequent addition of GM-CSF stimulated BeWo
      IL-10 secretion in a dose-related fashion. These results support the concept IL
      10 is expressed at the human maternal-fetal interface, and production of this
      important immunoregulatory molecule may be regulated, in part, by GM-CSF.

PMID- 10086070
TI  - Cell microchimerism in patients with recurrent spontaneous abortion: preliminary
      results.
AB  - The goal of this study was to determine the prevalence of non-host male cell
      microchimerism in a group of women with a history of recurrent spontaneous
      abortion (RSA). The detection of male cell microchimerism was based upon
      amplification of a fragment of Y chromosome DNA obtained from peripheral blood
      mononuclear cells from the mother. The amplification products were
      electrophoresed, transferred onto nylon membranes and hybridized with a specific
      32P-labelled probe. The products were visualized by autoradiography. Seventy
      seven patients with RSA were studied. Some patients (42.8%) had received
      immunotherapy for RSA using live mononuclear cells from male donors. Of the 77
      patients 46 (59.7%) were positive for the selected Y chromosome sequence, 22
      (28.6%) had no evidence of Y chromosome DNA and in nine (11.7%) cases the
      chimeric status could not be defined since the amplified band was too faint to be
      clearly assigned as positive. Twenty patients were pregnant at the time of
      sampling. There were no statistically significant differences among the different
      variables studied: age of the mother, number of previous pregnancies, number of
      previous immunotherapeutic inoculations or period of time between the last
      inoculation and sampling. Male cell microchimerism has been reported in some but
      not all women who have given birth to male children. The dynamics for the
      establishment of this chimeric status and its persistence have not been defined.
      We found that most patients with RSA (59.7%) were positive for microchimerism but
      that this could not be correlated with abortion, current pregnancy or leukocyte
      immunotherapy. A prospective study is being undertaken to determine if there is a
      subset of patients negative for chimerism who become positive after
      alloimmunotherapy with male lymphocytes and have an improved prognosis for
      successful pregnancy.

PMID- 10086071
TI  - Characterization of human chorionic gonadotropin peptide variants with a radio
      receptor assay using recombinant human luteinizing hormone/chorionic gonadotropin
      receptors.
AB  - There are potential interactions between various human chorionic gonadotropin
      (hCG) isoforms at the level of luteinizing hormone/chorionic gonadotropin (LH/CG)
      receptor. The objective of this study was to characterize the receptor-binding
      activities of the primary peptide variants of hCG including intact hCG, free beta
      subunit, beta-core fragment and nicked hCG, and to test the effects of these hCG
      variants on the binding of intact hCG. A radio-receptor assay based on cell
      membranes expressing recombinant human LH/CG receptors was validated and used in
      this study to avoid species differences in the receptor-binding specificity. The
      results showed that none of the hCG variants that we studied had sufficient
      binding affinity to compete with binding of intact hCG, nor were they able to
      antagonize the binding of intact hCG. These results suggest that hCG variants
      with either abbreviated polypeptide structures or incomplete peptide linkage are
      products or metabolites which do not have the tropic biological activity of the
      whole hormone, the intact heterodimeric hCG.

PMID- 10086072
TI  - Characterization of human chorionic gonadotropin in normal and abnormal
      pregnancies.
AB  - In this study circulating human chorionic gonadotropin (hCG) levels in the peri
      implantation period of natural cycles of normal women were characterized. The
      hypothesis that the bioactivity of hCG in abnormal pregnancies is different from
      that in normal pregnancies was tested daily through serum hCG measurements in two
      immunoenzymometric assays, a radioreceptor assay and a human luteinizing
      hormone/human chorionic gonadotropin--cyclic adenosine monophosphate--luciferase
      bioassay. In normal pregnancies, the levels of immunoreactive and bioactive hCG
      were higher than in abnormal pregnancies (p < 0.05). In addition, the slopes of
      the rise in concentration of hCG as measured in all four assays were
      significantly greater for normal pregnancies than for abnormal pregnancies (p <
      0.01). The rate of rise of hCG bioactivity was significantly greater than the
      rise of immunoreactivity or receptor-binding activity in normal pregnancies, but
      this difference was not observed in abnormal pregnancies. These results indicate
      that: (1) A steep rise of bioactive hCG is a consistent feature of the peri
      implantation period of normal pregnancies. (2) Abnormal pregnancies had a
      deficiency in the production of hCG, which was reflected in both the hCG levels
      and the rate of increase, even in the first week of implantation. (3) Some
      abnormal pregnancies produced hCG with lower biological activity than the hCG of
      normal pregnancies.

PMID- 10086073
TI  - Is the endometrial suction curette useful in the detection of chorionic villi
      during the first trimester?
AB  - OBJECTIVE: Early diagnosis of ectopic pregnancy is important for its medical
      management. Algorithms used for the diagnosis of ectopic pregnancy recommend
      obtaining a tissue diagnosis to rule out an intrauterine pregnancy when it is
      clear that a pregnancy is abnormal, but a stage of sonographic visualization has
      not been attained. The ability of an endometrial suction curette to identify
      products of conception early in pregnancy has not been documented. The purpose of
      this study was to determine the efficacy of an endometrial suction curette in
      detecting products of conception during the first trimester. METHODS: Twenty
      patients scheduled for termination of pregnancy via D&C agreed to endometrial
      sampling prior to dilatation of the cervix. All patients had transvaginal
      sonography which verified the gestational age. The specimen was evaluated
      microscopically after staining. RESULTS: Chorionic villi were identified in 14 of
      20 (70 per cent) specimens as seen with light microscopy. CONCLUSION: An
      endometrial suction curette identifies chorionic villi from an intrauterine
      gestation in the first trimester with a sensitivity of 70 per cent. While most
      patients with an intrauterine gestation can be identified using an endometrial
      suction curette to obtain trophoblastic tissue, the absence of this tissue does
      not definitively identify an ectopic pregnancy. Therefore, the routine use of the
      endometrial biopsy in the algorithms for the diagnosis and treatment of ectopic
      pregnancy should be approached with caution.

PMID- 10086074
TI  - Current progress in early pregnancy investigation.

PMID- 10086075
TI  - Insights into the mechanisms of vertical transmission of HIV-1. BIOMED2 Working
      Group on the in utero transmission of HIV-1.
AB  - This paper is a summary of three oral presentations, as well as the ensuing
      discussion, at the Rijeka/Opatija 3rd Alps Adria Immunology meeting by three
      members of the European Biomed group on vertical transmission of HIV (G. Chaouat,
      F. Barre-Sinoussi, G. Scarlatti). This group also involves the laboratories of D.
      Dormont (CEA, Fontenay aux roses, France), P. Gounon (Electron Microscopy, the
      Pasteur Institute, France; Irene Athanassakis, University of Crete, Greece; Eva
      Maria Fenyo, Karolinska Institute, Sweden; and Larry Guilbert, Canada). As such,
      this paper intends to be neither a review, nor an original article, but rather is
      an opinion paper discussing the working hypothesis of this network, as well as
      some of their recent results, which were presented at this meeting. The paper was
      issued at the request of the organizers of the meeting.

PMID- 10086076
TI  - Human endometrial decidual cell-associated 11 beta-hydroxysteroid dehydrogenase
      expression: its potential role in implantation.
AB  - During pregnancy excess corticosteroid exposure can disturb the normal pattern of
      growth and differentiation of the primate fetus. This is normally prevented by
      the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts
      cortisol to its biologically inactive 11-oxo form, thereby ensuring that little
      or no cortisol is transferred to the fetus. During implantation, extravillous
      trophoblasts breech uterine vessels that are embedded in a decidual cell matrix.
      Through this invasive process the embryo gains requisite access to the maternal
      blood supply, while risking exposure to high circulating glucocorticoid levels.
      Thus, the expression of 11 beta-HSD by the decidual cell layer may be essential
      in regulating cortisol exposure of the developing embryo prior to placentation.
      In order to investigate the potential contribution of decidual cells to
      glucocorticoid metabolism, we evaluated the expression of both known 11 beta-HSD
      isoforms, 11 beta-HSD1, whose catalytic activity is NADP(+)-dependent, and NAD(+)
      dependent 11 beta-HSD2, during decidualization of monolayers of human endometrial
      stromal cells. The differential actions of ovarian steroids on human endometrium
      are simulated in this in vitro model. Thus, progestins induce the expression of
      several decidualization markers in the cultured stromal cells, and consistent
      with its priming action in vivo, estradiol augments this expression. The results
      of our studies established a link between in vitro decidualization and enhanced
      glucocorticoid metabolizing capacity. Accordingly, the catalytic activities of
      both 11 beta-HSD isoforms were enhanced by incubation of the precursor stromal
      cells with medroxyprogesterone acetate, and further enhanced by estradiol,
      despite a lack of response to estradiol alone. This differential response to
      estradiol and progestin was reflected in parallel changes in steady state levels
      of 11 beta-HSD1 messenger RNA. The role of glucocorticoid metabolizing activity
      of the decidual cell is discussed in terms of its implications in determining the
      exposure of the implanting embryo to biologically active glucocorticoids.

PMID- 10086077
TI  - Localization of fos, jun, kit and SCF mRNA in human placenta throughout gestation
      using in situ RT-PCR.
AB  - The expression pattern of c-fos, c-jun, c-kit and stem cell factor (SCF) has been
      investigated in developing human placenta using the highly sensitive technique of
      in situ reverse transcriptase-polymerase chain reaction (RT-PCR). Specific
      transcripts of all genes under study were observed in first-trimester placenta
      sections. c-fos, c-jun, c-kit and SCF transcripts were localized in cells of the
      villous stroma; fos, jun and kit-specific mRNAs were also found in endothelial
      cells; fos, kit and SCF mRNAs were detected in villous trophoblast cells. In mid
      trimester and term placenta specimens only SCF transcripts were observed,
      restricted to trophoblast cells. The lack of c-fos transcripts in placenta from
      the second and third trimesters is a finding that contrasts with data from the
      literature obtained using extractive techniques. Parallel immunocytochemistry of
      placenta specimens from the three pregnancy stages under study revealed the fos
      protein only in first-trimester placenta, in agreement with the in situ RT-PCR
      findings. We conclude that the in situ RT-PCR technique is most suitable for gene
      expression studies because of its high level of sensitivity in correctly
      assigning the signal to specific cell types in complex tissues.

PMID- 10086078
TI  - Augmentation of DNA synthesis in placental and fetal tissues in utero by maternal
      growth hormone treatment.
AB  - The influence of maternal exogenous growth hormone treatment on in utero
      conceptus development was evaluated in the rat. The periods of response and
      stimulation of DNA synthesis on embryo/fetal and placental tissues were assessed
      by subcutaneous injections of ovine growth hormone (oGH) preparations during
      pregnancy days 11-15, autopsied on day 16; and during pregnancy days 11-20 and 16
      20, autopsied on day 21. To determine DNA biosynthesis potential, thymidine
      (methyl-3H) was administered through the jugular vein 14-16 h prior to sacrifice.
      DNA content and uptake of radiolabeled thymidine into DNA were analyzed for whole
      embryos on day 16, and for fetal liver, brain and remaining body tissues on day
      21 of pregnancy. Placental tissues from oGH-treated mother and controls were also
      quantified for DNA content and radiolabeled thymidine uptake. oGH treatment
      produced a significant increase (p < 0.05) in radiolabeled thymidine uptake into
      DNAs of different fetal organs compared to saline-treated controls matched for
      weight and litter number during the latter part of gestation (fetal histogenesis
      period; pregnancy days 16-20). The stimulatory influence of maternal growth
      hormone treatment on DNA contents and radiolabled thymidine uptake on placental
      tissues at this period of gestation was also significantly different from that of
      the controls. Rat conceptus tissues (embryos and placentas) during the
      organogenesis period of early gestation (days 11-15) appeared to be unresponsive
      to such treatment. Thus, these results suggest that maternal growth hormone
      influences conceptus growth during the latter part of gestation and activation of
      placental functions may be an important aspect of stimulation of cell
      proliferation in the rat fetus.

PMID- 10086079
TI  - Pregnancy detection by ultrasound and chorionic gonadotropin during the peri
      implantation period in the macaque (Macaca fascicularis).
AB  - The goal of these studies was to correlate sonographic evidence of pregnancy
      during the peri-implantation period with the timing of the rise in monkey
      chorionic gonadotropin (mCG) as measured with an enzyme-linked immunosorbent
      assay. Animals were time-mated at mid-cycle, and ultrasound examinations were
      performed on postovulation days 12-15 (n = 77). Pregnancy was sonographically
      identified in 48 of 77 animals (62.3%), of which 28 had correlative
      ultrasound/endocrine data collected. For these animals, blood samples were
      obtained on postovulation days 12-15 for mCG assay. Pregnancy was identified by
      ultrasound on postovulation days 12 (6/28; 21.4%), 13 (6/28; 21.4%), 14 (8/28;
      28.6%) or 15 (8/28; 28.6%). Seven of the 28 (25.0%) were found to have mCG levels
      consistent with pregnancy (> or = 1 ng/ml) on the same day as ultrasound
      confirmation, 12 of 28 (42.9%) were sonographically detected as pregnant 1 (n =
      6), 2 (n = 3) or 3 (n = 3) days earlier than by mCG, and nine of 28 (32.1%) were
      found to have elevated mCG levels 1 (n = 7), 2 (n = 1) or 3 (n = 1) days earlier
      than ultrasound confirmation of pregnancy. The results of these studies have
      demonstrated (1) the utility of anatomical and endocrine techniques for detecting
      pregnancy approximately 3 days after the onset of implantation, and (2) the
      variation in the timing of implantation and the rise in circulating mCG in
      individual animals.

PMID- 10086080
TI  - The relationship between trophoblast differentiation and the production of
      bioactive hCG.
AB  - We previously showed that a significant number of failing pregnancies are
      associated with production of human chorionic gonadotropin (hCG) having
      relatively low bioactivity. The present study was designed to compare the
      secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during
      trophoblast differentiation, and to test the hypothesis that the lower bioactive:
      immunoreactive hCG ratios in failing pregnancies are related to reduced or
      impaired trophoblast differentiation. Cytotrophoblast cells were isolated from
      term placentas and cultured under conditions that induced or did not induce
      syncytiotrophoblast formation. Culture media were collected at regular intervals
      up to 72 h and levels of immunoreactive and bioactive hCG were measured. The
      differentiation of cytotrophoblast cells to multinucleated syncytiotrophoblast
      was monitored by immunocytochemistry and electron microscopy. During the 72 h
      culture period, concentrations of immunoreactive and bioactive hCG increased in
      both differentiating and non-differentiating cells. However, the concentrations
      of immunoreactive and bioactive hCG were higher under culture conditions that
      promoted trophoblast differentiation. Furthermore, the ratio of bioactive hCG to
      immunoreactive hCG was higher in differentiating cultures. When differentiation
      was inhibited by dimethyl sulfoxide, the secretion of bioactive hCG was reduced
      and the bioactive: immunoreactive hCG ratio did not change. These findings are
      consistent with the idea that production of bioactive hCG accompanies
      syncytiotrophoblast formation.

PMID- 10086081
TI  - Less miscarriage in pregnancy following Tamoxifen treatment of infertile patients
      with luteal phase dysfunction as compared to clomiphene treatment.
AB  - OBJECTIVES: To compare the efficacy and the reproductive outcomes of Tamoxifen
      (TMX) vs. clomiphene citrate (CC) treatment in infertile women with luteal phase
      dysfunction. METHODS: Eighty-seven consecutive infertile women with luteal phase
      dysfunction were randomly assigned to two treatment groups as: group 1 (TMX
      followed by CC) and group 2 (CC followed by TMX). The medications administered in
      the initial and the subsequent cross-over phase were given for 4 to 6 cycles
      except in those patients who achieved pregnancy within the first three cycles of
      treatment. The rates of pregnancy, spontaneous abortion and live-birth were
      calculated for comparison. Demographic profile and the frequency of other
      infertility factors between the two groups were comparable. RESULTS: The
      pregnancy rates were similar between TMX and CC treatment (initial treatment
      phase: TMX, 50.0% vs. CC, 56.4%; subsequent treatment phase: CC, 33.3% vs. TMX,
      47.1%), but the abortion rates were significantly lower (p < 0.05) in TMX
      treatments (initial treatment phase: 8.3% and subsequent treatment phase: 12.5%)
      than that of CC treatments (initial treatment phase: 22.7% and subsequent
      treatment phase: 62.5%). When the rates were calculated by pooling the patients
      according to the medication they received, the miscarriage rate was significantly
      lower (p < 0.05) if the patients conceived during the TMX treatment (9.4% vs. CC,
      33.3%). CONCLUSIONS: Tamoxifen and clomiphene citrate seem to be similarly
      effective in achieving pregnancy in patients with luteal phase dysfunction.
      However, Tamoxifen therapy is associated with a lower incidence of spontaneous
      abortion; thus Tamoxifen may be the better choice for the therapy of infertile
      women with luteal phase dysfunction.

PMID- 10086082
TI  - The long-term effects of pregnancy and bromocriptine treatment on prolactinomas-
      the value of radiologic studies.
AB  - OBJECTIVE: To evaluate the long-term effects of pregnancy and bromocriptine
      treatment on prolactin-secreting pituitary tumors in women undergoing infertility
      treatment for prolactinomas. METHODS: The records of 17 patients with
      prolactinomas were reviewed. Data regarding age, prepregnancy baseline and
      postpartum serum prolactin levels, and radiologic studies including CT or MRI
      were assessed. 16 patients were treated with bromocriptine before achieving
      pregnancy. Bromocriptine therapy was resumed after delivery for the duration of 1
      to 14 years. RESULTS: 45% of pregnancies did not affect the size of
      prolactinomas, 27% of pregnancies showed a decrease in size of prolactinomas or
      radiologic evidence of resolution of the tumor and 27% of pregnancies
      demonstrated radiologic increase in the size of prolactinomas. CONCLUSIONS: It is
      safe for patients with prolactinomas to achieve pregnancy following bromocriptine
      treatment. Pregnancy may lead to a slight decrease in the size of prolactinomas,
      increase in size, no change, and in some cases, complete resolution. There were
      no visual field changes during the pregnancies. Pregnancy and long-term
      bromocriptine treatment may be helpful in reduction of the size of the tumor.

PMID- 10086083
TI  - A re-examination of the association of 'early pregnancy factor' activity with
      fractions of heterogeneous molecular weight distribution in pregnancy sera.
AB  - The association of 'early pregnancy factor' ('EPF') activity in early pregnancy
      sera with multiple fractions of heterogeneous molecular mass was re-examined to
      test whether previously perplexing observations could be explained by a new multi
      factorial model of the serum components required for this activity expression.
      Gel permeation fractionation of human pregnancy sera revealed 'EPF' activity
      associated with fractions containing components ranging in MW from < or = 1 kDa
      to > or = 500 kDa. A significant activity peak was observed eluting on the total
      volume (Vt) of the column, indicating the presence of active molecules of very
      low molecular mass. Multiple activity peaks were also observed in the
      macromolecular fractionation region ranging in apparent molecular weight from 12
      kDa, through 25, 70 and 250 to > or = 500 kDa. Analysis of these fractions
      revealed that they all contained thioredoxin and active moieties of low molecular
      mass, with the latter probably directly associated with the former. Adsorption
      with specific anti-thioredoxin antibodies removed from these fractions the
      capacity to display 'EPF' activity. Further analyses revealed that in these
      fractions thioredoxin played a permissive role allowing the low molecular mass
      active moieties to express activity in the bioassay in the presence of otherwise
      counteracting substances. The results of these studies are consistent with the
      proposal that 'EPF' activity expression in pregnancy sera is due to the presence
      of a multi-factorial system in which thioredoxin plays an essential permissive
      role in concert with active moieties of low molecular mass.

PMID- 10086084
TI  - Fetal rat brains contain luteinizing hormone/human chorionic gonadotropin
      receptors.
AB  - The reverse transcription-polymerase chain reaction/Southern, Northern and
      Western blottings demonstrated that 19-day-old fetal rat brains contained the
      luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor transcripts
      and receptor protein. Further investigation with Western blotting demonstrated
      that diencephalon, mesencephalon, rhombencephalon and telencephalon and several
      areas in each of these regions contained the LH/hCG receptor protein. The
      receptor protein levels in different regions were somewhat variable but they were
      not different from each other or from the whole brain. The 15-day-old fetal rat
      brains contained lower receptor protein levels which increased by 3-fold in 17
      day-old and by 12-fold in 19-day-old fetal rat brains with no further significant
      increase in 21-day-old fetal, neonatal or adult rat brains. In summary, fetal rat
      brains contained LH/hCG receptors and these receptors were developmentally
      regulated. These findings suggest that the gonadotropins LH and hCG may regulate
      growth, development and differentiation in fetal brain.

PMID- 10086085
TI  - Can luteal phase serum estradiol concentrations predict karyotypes of spontaneous
      abortions?
AB  - Low serum estradiol concentrations during pregnancy have been associated with
      spontaneous abortions. A large proportion of abortuses have chromosomal
      abnormalities. To determine whether serum estradiol during the luteal phase of
      conception cycles can predict the karyotype of spontaneous abortions, serum
      estradiol samples were drawn 11 days after embryo transfer from 52 women who
      subsequently had spontaneous abortions and chromosomal analysis was performed on
      the products of conception. The frequency of estradiol levels < 100 pg/ml was
      compared between normal and abnormal karyotypic spontaneous abortions.
      Chromosomal analyses among 52 spontaneous abortions revealed 14 (27%) to be
      normal and 38 (73%) abnormal. Among the 38 karyotypic abnormalities 30 were
      aneuploidy and eight were polyploidy. Serum estradiol levels were < 100 pg/ml in
      eight women (15%) and > 100 pg/ml in 44 women (85%). The frequencies of estradiol
      < 100 pg/ml in spontaneous abortions with normal (7%) and abnormal (18%)
      karyotypes were not significantly different. Thus, serum estradiol cannot predict
      the karyotype of spontaneous abortions.

PMID- 10086087
TI  - [50 years of clinical trials; a new direction in medicine].
AB  - In 1998 the medical community commemorated the completion of the first truly
      randomised trial, the Medical Research Council Streptomycin Study. This invention
      is at least as important as Harrison's clocks, which in the 18th century solved
      the problem of measuring longitude at sea. Naturally the idea of randomised
      controls had evolved from previous notions. Obtaining informed consent remains
      essentially a matter between patient and physician, but in the meantime four
      other interested parties have joined in: governing bodies, the pharmaceutical
      industry, medical journals, and the mass media. In order to keep all these forces
      in check, lawmakers should protect the weakest parties against the more powerful
      ones. There is a great deal to be done in the next 50 years.

PMID- 10086088
TI  - [Parvovirus B19 infection in pregnancy: a cause of non-immune hydrops fetalis].
AB  - Four pregnancies, in two women aged 39 and two women aged 34 years respectively,
      were complicated by foetal parvovirus B19 infection. First-trimester intrauterine
      death resulting from multiple congenital anomalies was diagnosed in one patient
      with proven foetal parvovirus B19 infection. In three patients foetal hydrops was
      found in the second trimester with variable clinical course. In one of them,
      foetal hydrops resulted in second-trimester foetal death; in another, foetal
      hydrops resolved following intrauterine blood transfusion and in a third foetal
      hydrops resolved spontaneously. Foetal parvovirus B19 infection was diagnosed by
      polymerase chain reaction (PCR) using foetal cells obtained by amnioscentesis. It
      is concluded that maternal parvovirus B19 infection is mostly asymptomatic.
      However, the clinical impact of maternal infection on the foetus is diverse, i.e.
      infection may result in foetal death or--transient--foetal morbidity, in
      particular foetal anaemia. In mothers with proven foetal parvovirus B19 infection
      close monitoring of the foetus by ultrasound is warranted. Occasionally
      intrauterine transfusion is required. From the literature to date, the estimated
      incidence of maternal parvovirus B19 infection in pregnancy is 3-7%. The vertical
      transmission rate approximates 30%. When pregnancy is complicated by foetal
      hydrops foetal parvovirus B19 infection should be kept in mind.

PMID- 10086089
TI  - [Supervision of medical scientific research with mentally competent subjects is
      impossible without reviewing].
AB  - The object of reviewing medical scientific research in humans is to offer
      guarantees against, especially, violations of physical integrity and privacy.
      Since the scientific interest is a matter of first importance, the research has
      to be checked for its reasonableness and for the test subject's consent. Omission
      of these checks in case the risk or stress to be expected is slight is contrary
      to these criteria. Reversion of the sequence of informed consent and
      randomization is contrary to the requirement of consent. Free, informed consent
      may be assumed if in a trial with a control group the test subject is informed
      beforehand about the study design and the risks, but is not told if he is to
      receive a standard therapy, a placebo or a test medication.

PMID- 10086090
TI  - [Preeclampsia not (yet) predictable from the blood platelet count].
AB  - Platelet activation plays an important role in the pathogenesis of pre-eclampsia
      as demonstrated by reduced platelet count, increased mean platelet volume and
      elevated plasma concentrations of beta-thromboglobulin and platelet factor 4 in
      pre-eclamptic patients. Thrombocytopenia precedes the onset of clinical symptoms
      of pre-eclampsia. Possibly an enhanced activation state of the platelets in the
      circulation is present some time before the onset of pre-eclampsia: platelet
      activation might then be used to predict pre-eclampsia. Flow cytometry is
      considered the most sensitive technique at this moment to measure the activation
      of platelets. Fluorescent-labelled antibodies are used to detect antigens that
      appear on the platelet surface or change their conformation upon activation.
      During the first and second trimester of pregnancy pre-eclamptic patients have an
      increased expression of some antigens on the surface of their platelets, such as
      CD63. There is no reliable platelet test yet to predict the onset of pre
      eclampsia.

PMID- 10086091
TI  - [The treatment of chronic fissure in ano with nitrate ointment].
AB  - A chronic anal fissure may be regarded as an ischaemic ulcer. Until recently, its
      treatment necessitated surgical intervention to lower the tension of the internal
      sphincter (lateral internal sphincterotomy), or manual dilatation of the anus. A
      disadvantage of both methods is the risk of permanent sphincter injury resulting
      in reduced continence. Local application of ointment containing nitroglycerin
      (glyceryltrinitrate) or isosorbide dinitrate reduces the pressure at rest in the
      anal canal and increases the anodermal blood circulation. Both ointments in most
      patients lead to healing of the chronic anal fissure. Nitroglycerin ointment in a
      prospective, randomized trial brought about better healing than placebo
      treatment. The advantage of the ointment treatment, the needlessness of
      sphincterotomy, is particularly important in cases of existing sphincter
      abnormalities. It has the disadvantage that it takes longer for the fissure pain
      to abate. The principal side effect is headache. In over 50% of the patients the
      treatment has to be continued for longer than 6 weeks. Little is known as yet
      about the risk of recurrence. Before surgical interventions as the treatment of
      first choice can be definitely replaced by treatment with nitrate ointment the
      good results of the ointment treatment have to be confirmed. Also, more has to be
      found out about the risk of recurrence, the optimal duration of the treatment and
      the choice of the type of nitrate ointment.

PMID- 10086092
TI  - [Clinical thinking and decision-making in practice. A child with dyspnea and
      excess pleural fluid].
AB  - Pleural fluid was diagnosed on an X-ray in a 9-month-old boy with acute dyspnoea
      without fever. Thoracentesis showed exudate and the patient was diagnosed as
      having empyema and was treated with continuous chest tube drainage and
      antibiotics. The culture of the pleural fluid was negative. A month after
      discharge the boy developed recurrent pleural effusion with dyspnoea. A mass in
      the right hemithorax was found upon additional diagnostic evaluation. Microscopic
      evaluation of tumour biopsy specimen showed a malignancy. Infantile fibromatosis
      was diagnosed in a surgical specimen. The patient died after having developed a
      recurrent tumour. Infectious causes are not likely in a child with pleural fluid
      without fever. Pleural fluid has to be analysed in transudate or exudate. Exudate
      requires a complete diagnostic evaluation.

PMID- 10086093
TI  - [Prevalence of osteoporosis in postmenopausal women in family practice].
AB  - OBJECTIVE: To assess the prevalence of osteopenia, osteoporosis and severe
      vertebral deformities in general practice. DESIGN: Cross-sectional study.
      METHODS: Of a randomly selected group of 712 women aged 55 to 84 years in a
      general practice in Noordwijk, the Netherlands, 449 (63%) participated in a study
      in 1996, in which Dual Energy X-ray Absorptiometry (DXA) of the femoral neck was
      performed: in 428 women vertebral morphometry of lateral radiographs of the spine
      was also done. The World Health Organization definitions of osteopenia and
      osteoporosis were used. RESULTS: The mean bone mineral density (BMD) was 0.866
      g/cm2 (SD: 0.135). With increasing age the BMD decreased statistically
      significantly by 0.0073 g/cm2/year. There were 189 women with osteopenia (42%).
      33 (7%) with osteoporosis and 44 (10%) with one or more severe vertebral
      deformities. A significantly lower mean BMD was found in those with severe
      vertebral deformities than in those without.

PMID- 10086094
TI  - [Tinea capitis in primary school age children in southeastern Amsterdam:
      primarily due to Trichophyton tonsurans].
AB  - OBJECTIVE: To establish prevalence and aetiology of tinea capitis in children
      attending primary school in Amsterdam South-East. DESIGN: Prevalence survey.
      METHODS: The Municipal Health Service Amsterdam, the Netherlands, selected
      classes of four primary schools in a survey with children clinically suspected of
      having tinea capitis as well as classes without clinical cases. Per school at
      least one class with a notified case was included. Written information was
      provided to all parents; the parents of three children refused participation.
      After clinical examination by a team of physicians and nursing staff scalp
      cultures were taken using the brush method from 315 children (aged 4-12 years) in
      16 classes. RESULTS: The clinical diagnosis 'tinea capitis' was established in 25
      children, significantly more in boys than in girls (relative risk (RR) = 2.92:
      95% confidence interval (95% CI) 1.20-7.11). Of all children 7% had positive
      cultures, more boys than girls (RR = 3.13: 95% CI: 1.18-8.28). Symptomatic cases
      (confirmed by culture) amounted to 3.2% of all children. The carrier rate was
      3.8%. Trichophyton tonsurans was the most frequently isolated dermatophyte both
      in symptomatic children and in carriers. CONCLUSION: In 7% of all children (3.2%
      with symptoms of tinea capitis, 3.8% without) dermatophytes were cultured from
      scalp samples, the main aetiologic agent being T. tonsurans.

PMID- 10086095
TI  - [Pregnancy outcome after ecstasy use; 43 cases followed by the Teratology
      Information Service of the National Institute for Public Health and Environment
      (RIVM)].
AB  - OBJECTIVE: To determine if use of ecstacy during pregnancy has any harmful
      effects on pregnancy and the (unborn) child. DESIGN: Prospective, descriptive.
      METHODS: After the Teratology Information Service of the National Institute of
      Public Health and the Environment. Bilthoven, the Netherlands, was approached by
      a physician or midwife for information, the pregnancies that involved the use of
      ecstacy were followed by a follow-up questionnaire one month after the estimated
      date of birth. RESULTS: A total of 49 pregnancies were followed. For 43 women,
      exposed early in pregnancy, data on course of pregnancy and health of baby are
      known. There were 3 elective terminations of pregnancy and 2 spontaneous
      abortions. There were 40 live-born babies (including one set of triplets); one of
      them had a congenital cardiac malformation. Beside ecstacy the mothers frequently
      also used other substances potentially harmful to pregnancy and child. The
      pregnancies were often unplanned; previous pregnancies had frequently been
      terminated. CONCLUSION: The sample size was too small to draw conclusions. As yet
      spontaneous abortions and congenital malformations did not appear to occur more
      frequently in pregnancies with use of ecstacy. The lifestyle of the ecstacy users
      seemed to be potentially harmful for pregnancy and child.

PMID- 10086096
TI  - [The use of an implantable ECG recorder in the diagnosis of puzzling sporadic
      syncopes].
AB  - A 70-year-old man had passed out three times in six years, and was suspected of
      having a rhythm or conduction disturbance. Repeated hospitalization with
      telemetric monitoring had not revealed any disease. An implantable ECG recorder
      finally revealed the occurrence of symptomatic sinus arrest (Adams-Stokes
      attack), a month after discharge from the hospital. The patient was treated with
      a pacemaker. The cause of recurrent syncope can be difficult to diagnose. There
      is always a danger of overdiagnosis or under-treatment. Prospective study and
      cost effectiveness analysis are needed to determine the proper place of the
      implantable ECG recorder in the diagnosis of this disease.

PMID- 10086097
TI  - [Emphasizing of ethical criteria for medical scientific reporting and the
      Declaration of Helsinki].
AB  - The 'Bill on Medical Scientific Research with Humans' is about to be introduced
      in the Netherlands. Clinicians who have scientific interests when carrying out
      diagnostic and therapeutic procedures and who are not solely motivated by the
      well-being of their patients are subject to a potential conflict of interests.
      The Declaration of Helsinki, of which a Dutch integral version is presented,
      deals with the pertinent ethical guidelines. The 'Uniform requirements for
      manuscripts submitted to biomedical journals' (so-called Vancouver rules)
      stipulate that research should be in accordance with the Helsinki statements.
      Journal editors may ask authors to produce the written approval of their research
      by an ethical committee. With respect to the disclosure of patient data in
      scientific articles, which in principle requires informed consent of the patients
      concerned, it is the policy of this journal to anonymize the data when the paper
      is edited in such a way that people other than the patients themselves are
      unlikely to recognize the patients. If this is not possible explicit written
      consent of the patients is required.

PMID- 10086098
TI  - [The SGO Health Research Promotion Program. XIII. Evaluation of the section
      'Addiction Research'].
AB  - As a part of the SGO Health Research Promotion Programme a research programme on
      addiction research was realized. Aim of the programme was to strengthen and
      concentrate the Dutch research into addiction. Within the Amsterdam Institute for
      Addiction Research (AIAR), a structural collaboration between the Jellinek
      Treatment Centre for Addiction, the University of Amsterdam and the Academic
      Hospital of the University of Amsterdam, strategic research programmes were
      developed on the borderland of addiction and psychiatry, notably 'Clinical
      epidemiology addiction' and 'Developmental disorders, addiction and
      psychotraumas'. The institution of a co-ordinating platform of research groups
      conducting socio-epidemiological addiction research improved the co-ordination of
      research lines in this field.

PMID- 10086099
TI  - [The SGO Health Research Promotion Program. XIV. Final evaluation].
AB  - In the Netherlands, the SGO Health Research Promotion Programme was carried out
      from 1986 until 1997. The aim of the programme was to strengthen patient-oriented
      clinical research in specific fields of medicine. Some of the programme sections
      certainly produced a number of good publications in established national and
      international journals, but the programme advisory committee's main objective was
      to bring about a cultural change in the field of health care investigation:
      awareness of the principle that scientific and notably patient-centred
      investigation has a place in its own right in research, education and care. This
      resulted in a large diversity of methods of stimulation ranging from stimulation
      of co-operation between researchers, training of physician researchers, support
      of methodology development, stimulation of education and postgraduate training,
      to establishment of actual institutes for clinical scientific research. Patient
      oriented research is the necessary link within the continuum of health research,
      medical education and care. Changing social and demographic developments ask for
      continuous innovation of this type of research. Top-down steering, as practised
      by the SGO, can be necessary and effective to reach this innovation.

PMID- 10086100
TI  - [Medical scientific research with people: what the law does not regulate].
AB  - The 'Bill on Medical Scientific Research with Humans' fail to state clearly which
      research may and which research may not be carried out without previous approval
      from a review committee. This is a problem especially with regard to studies
      using human body material and studies involving questioning people to collect
      study data. For the sake of clarity in practice it would be advisable if
      researchers and review committees would observe the following rules: every
      planned research project which involves patients or other persons having to do or
      to undergo something for the special purpose of the study must be submitted by
      the researchers to a review committee. However, actual reviewing is only
      necessary in the case of studies which, in the review committee's opinion, entail
      a real health risk or cause significant physical inconvenience or mental stress.
      Research involving persons who are vulnerable with respect to self-determination,
      such as the mentally incompetent, should always be reviewed, even if it does not
      seriously threaten the subjects' physical or mental well-being.

PMID- 10086101
TI  - [The risk of ingestion of cleaning tablets for dentures and dental prostheses].

PMID- 10086102
TI  - [The risks from ingestion of cleaning tablets for dentures and dental
      prostheses].

PMID- 10086103
TI  - [Chemotherapy in metastasized breast cancer].

PMID- 10086104
TI  - [Elective cesarean section preferably after completion of a minimum of 38 weeks
      of pregnancy].

PMID- 10086105
TI  - [Vascular brain damage: an important and recognizable cause of cognitive and
      behavioral disorders].
AB  - Four patients presented symptoms of a dementia syndrome. A man aged 67 showed
      gradual aggravation of disorders of memory and gait, as well as subcortical
      infarctions. A man aged 65 had disorders of concentration non compatible with the
      infarctions on the MRI scan, which disappeared after discontinuation of use of
      flunarizine. A woman aged 55 and a man aged 52 had changes of character and
      infarctions in the frontal lobe. Vascular dementia is, contrary to what most
      criteria suggest, often a subcortical syndrome. The relationship between
      cerebrovascular pathology on CT and MRI scans and cognitive and behavioural
      disorders is often hard to establish. If the criteria for vascular dementia are
      applied blindly, other causes of the subcortical dementia syndrome can be missed.
      The present criteria offer almost no room for detecting the subtle cognitive and
      behavioural disorders of cerebrovascular pathology. It is important to recognize
      the early changes of a threatened brain, because treatment and prevention might
      be effective in preventing further damage.

PMID- 10086106
TI  - [Locoregional radiotherapy after mastectomy and chemotherapy for breast cancer:
      prolonged survival and better local tumor control].
AB  - In two recent randomized clinical trials from Denmark and Canada the usefulness
      of radiotherapy was evaluated in premenopausal patients with breast cancer who
      had been operated and in whom the findings indicated a poor prognosis. Over 2000
      patients participated. After follow-up periods of 10 and 15 years, respectively,
      addition of locoregional therapy to mastectomy and chemotherapy with
      cyclophosphamide, methotrexate and fluorouracil (CMF) was found to result in
      better locoregional control and a better disease-free survival. These studies
      also demonstrated, for the first time, that the overall survival was increased
      after postoperative radiotherapy. In view of these findings, the indication for
      postoperative locoregional radiotherapy in breast cancer in the Netherlands
      should be reconsidered.

PMID- 10086107
TI  - [Locoregional radiotherapy after mastectomy not useful for all Dutch breast
      cancer patients].
AB  - Two recent randomized clinical trials from Denmark and Canada show that
      postoperative radiotherapy of breast cancer patients in whom the findings
      revealed a high risk of dying from the disease not only causes improvement of the
      locoregional tumour control but also prolongs survival. However, this does not
      establish definitely which patients belong to this 'high risk category'. Results
      of retrospective studies from Leiden suggest that selective withholding of
      postoperative radiotherapy in the Netherlands is justified for large groups of
      breast cancer patients. Both clinically manifest parasternal recurrences and
      axillary recurrences are rare among these patients. The condition is, however,
      that the axillary dissection is radical and performed properly.

PMID- 10086108
TI  - [Hyperthermia in combination with radiotherapy].
AB  - The clinical application of hyperthermia in the treatment of oncological patients
      is based on a strong biological rationale: hyperthermia is an effective cell
      killing agent, the effects of which can be induced selectively in tumour tissue.
      The mechanism of action of hyperthermia is complementary to that of radiotherapy
      (and chemotherapy). Furthermore, hyperthermia enhances the effects of
      radiotherapy (and of chemotherapy). In the approximately 20 years that
      hyperthermia was clinically investigated, much progress was made in the
      techniques of application. The clinical results achieved so far show that the
      therapeutic gain by adding hyperthermia can indeed be substantial.

PMID- 10086109
TI  - [Re-irradiation with hyperthermia in patients with recurrent breast cancer].
AB  - In the Daniel den Hoed Cancer Centre in Rotterdam, the Netherlands, patients with
      recurrent breast cancer within a previously irradiated area, are treated by
      application of hyperthermia in addition to reirradiation. In this development,
      the following issues are important: (a) the choice of an effective and tolerable
      reirradiation schedule; (b) the establishment of the limitations of the
      hyperthermia techniques available; (c) the finding that additional hyperthermia
      has to be applied to the total tissue volume at risk for tumour recurrence; (d)
      the assessment of the value of additional hyperthermia by a randomised study.
      With the reirradiation schedule of 8 x 4 Gy and the hyperthermia application
      technique at present available, local control is achieved in 76% of the patients
      for a median duration of 32 months. The probability of local control is related
      to tumour size. The treatment is tolerated well, with acceptable toxicity. In
      patients with recurrent breast cancer in a previously irradiated area, combined
      reirradiation and hyperthermia is very effective, well tolerated and little
      toxic.

PMID- 10086110
TI  - [Hyperthermia in combination with chemotherapy in gynecological cancers].
AB  - Hyperthermia in combination with chemotherapy has a strong biological rationale
      based on thermal enhancement of cytotoxicity and partial circumvention of
      resistance. Weekly locoregional hyperthermia in combination with cisplatin is an
      effective treatment (response rate: 52%) for patients with a recurrence of a
      previously irradiated carcinoma of the uterine cervix. A comparative trial versus
      cisplatin alone was recently started. Hyperthermic intraperitoneal chemotherapy
      is aimed at situations after optimal cytoreductive surgery in patients with
      carcinomatous peritonitis. The warmth enhances the penetration of the oncolytic
      agent. Whole-body hyperthermia using the Aquatherm apparatus in combination with
      chemotherapy is feasible: results in patients with metastatic sarcomas are
      promising. Trials with whole-body hyperthermia are in progress in patients with
      platinum refractory ovarian cancer and in patients with a metastatic carcinoma of
      the uterine cervix.

PMID- 10086111
TI  - [Towards an accreditation system for the Dutch hospitals].
AB  - The development of the Netherlands system for accreditation of hospitals started
      in 1989 in the Pilotproject Accreditation (PACE). This resulted in the
      establishment of the Netherlands Institute for Accreditation of Hospitals (NAIH)
      early 1999, by the Dutch Association of Hospitals, the Dutch Association of
      University Hospitals, the Dutch Organisation of Medical Specialists and the PACE
      foundation. Dutch hospitals may request (voluntary) for an accredition for their
      whole organisation or for parts of it, independent of the used quality system. An
      accreditation assesses whether organizational requirements are available for
      quality assurance. Accreditation is not primarily aimed to account for
      organizational quality, but rather to find points for improvement. The survey is
      carried out by peers: experts from other Dutch hospitals. The frame of reference
      used in accreditation is composed of 35 departmentwise standards and a
      hospitalwide standard 'Quality system'. All standards are developed by people in
      Dutch hospitals. NIAH can accept certificates for parts of the hospital (e.g.
      laboratoria) issues by organisations. The system is complementary to the
      'visitities' which are organized by the medical specialist societies in the
      Netherlands. From 1996-1998 trial accreditations were carried out in 19 Dutch
      hospitals. These showed that the accreditation system has an added value for
      Dutch hospitals.

PMID- 10086112
TI  - [Chronic polypharmacy in one-third of the elderly in family practice].
AB  - OBJECTIVE: Description of the extent and nature of polypharmacy in the elderly in
      general practice. DESIGN: Retrospective cross-sectional study. METHOD: Medication
      and morbidity data were collected over July-December 1994 on all 2197 patients >
      or = 65 years registered in 3 family practices connected with the Medication and
      Morbidity Registration Network Groningen, the Netherlands. Special attention was
      paid to the simultaneous use of > or = 2 drugs during > or = 120 days in the
      study period ('chronic use'). Three categories of polypharmacy were
      distinguished: mild (2-3 drugs), moderate (4-5) and extensive (> 5). RESULTS:
      Forty per cent of the study group were males; 54% were 65-74 years, 34% were 75
      84 years and 12% were > or = 85 years. The mean number of drugs used was 3.9 per
      person (SD: 3.6), of which 1.4 (SD: 1.8) chronically. Polypharmacy occurred in
      35%: mild in 23%, moderate in 8% and extensive in 4%. All occurred mostly in the
      group between 75 and 84 years old. Cardiovascular drugs, in particular diuretics,
      and psycholeptics were mostly prescribed concomitantly with each other and with
      other drugs. The prevalence of concomitant use of drugs with potential
      interactions was low (< 3%). The indications for psycholeptic drugs were quite
      often not clear. Congestive heart failure, chronic obstructive pulmonary disease
      (COPD)/asthma and diabetes mellitus were mainly responsible for extensive
      polypharmacy.

PMID- 10086113
TI  - [Prophylactic total thyroidectomy in childhood for multiple endocrine neoplasia
      type 2A: preliminary results].
AB  - OBJECTIVE: Evaluation of prophylactic total thyroidectomy in childhood in case of
      MEN2A gene carriership. DESIGN: Retrospective. METHOD: Prophylactic thyroidectomy
      was performed in 14 MEN2A gene carriers (7 boys, 7 girls; median age 9.1 year
      (range: 4.8-14.7)), in June 1993-July 1997 at the department Pediatric Surgery of
      the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Median time
      between genetic investigation and operation was 5.5 months (range: 2-35). Lymph
      node dissection was not performed. The parathyroids were identified and left
      untouched as far as possible, autotransplantation was performed twice because of
      doubt about viability. Outpatient follow-up took place every 3-6 months. RESULTS:
      One patient (13.4 year) showed macroscopic, the other 13 microscopic multifocal
      medullary thyroid carcinoma, 11 bilateral and 3 unilateral. In 1 child (6.2 year)
      neuroinvasive growth existed already. Surgical sections were free of tumour.
      After the operation temporary hoarseness occurred once, temporary hypocalcaemia
      three times and permanent hypoparathyroidism twice; after autotransplantation no
      hypocalcaemia occurred. Median follow-up was 3.2 year (range: 1 month-4.0 year).
      Mild psychological problems were observed in 4 patients, psychiatric problems in
      1. CONCLUSION: Prophylactic total thyroidectomy during the first decade is
      recommended. Additional lymph node dissection and total parathyroidectomy are
      unnecessary than. In order to prevent postoperative hypoparathyroidism,
      autotransplantation of at least one parathyroid is advisable.

PMID- 10086114
TI  - [Pleural amyloidosis as a cause of excessive pleural effusions].
AB  - A 83-year-old woman known with a stable disease multiple myeloma was hospitalized
      frequently with dyspnoea caused by copious bilateral pleural effusions.
      Thoracentesis was performed repeatedly but pleural effusions returned. Extensive
      laboratory and radiological examinations failed to reveal the cause of the
      pleural effusions. Finally, after pleural biopsy the diagnosis of amyloidosis of
      the pleura could be made. The patient died in hospital from a stroke. Pleural
      amyloidosis is rarely reported and is accompanied by large uni- or bilateral
      pleural effusions even without amyloidosis of the heart.

PMID- 10086115
TI  - [Foot-and-mouth disease of cattle is not a zoonosis].
AB  - In 1997 there was an outbreak of foot-and-mouth disease (FMD) among cattle in
      Turkey. People visiting that country were warned against importing animal
      products into the Netherlands. This had nothing to do with hazards to human
      health, as FMD virus is not a zoonotic virus, but with the risk of spread of the
      disease to livestock in the Netherlands, notably to cattle and pigs. A disease
      with similar clinical symptoms in pigs is swine vesicular disease (SVD), which is
      not a zoonosis either. FMD virus is an aphtovirus, SVD virus is an enterovirus.
      Hand-foot-and-mouth disease in humans is caused by other enteroviruses, i.e.
      Coxsackie virus and enterovirus 71.

PMID- 10086116
TI  - [The Law on (Re)integration of Disabled Persons].
AB  - In spite of the growing economy, with diminishing unemployment and increasing
      scarcity of manpower, many people with chronic health problems remain unemployed.
      To promote their participation in the labour progress, the Law on (Re)integration
      of Incapacitated Persons (REA) was enacted on 1 July 1998. This law provides a
      number of facilities for those classified as 'unable to work'; These are persons
      impaired by chronic health problems in participating in the labour process. The
      existing allowances have been liberalized and simplified considerably. Employers
      in certain cases can expect substantial subsidies. In addition, there are more
      facilities like vocational re-education and psychological and other training
      courses. The concept of 'incapability' is rather vague. Fortunately, the Law
      makes it immediately clear who may be regarded as incapable. In other cases,
      physicians employed by Factories Act organizations, employment policy offices and
      social insurance will have to take part in the evaluation. The new law has a few
      paradoxical starting points, those incapable for work are given hardly any voice
      and there is a clear risk of stigmatization. On the other hand, failure of the
      (re)integration of handicapped persons into the labour process may lead to
      further encroaching upon the welfare state.

PMID- 10086117
TI  - [Transanal endoscopic microsurgery: a good possibility for local resection of
      rectal tumors].

PMID- 10086118
TI  - [Transanal endoscopic microsurgery: a good possibility for local resection of
      rectal tumors].

PMID- 10086119
TI  - [Thalidomide once more in the spotlight].

PMID- 10086120
TI  - [Cholinesterase inhibitors in Alzheimer disease: preliminary recommendations for
      the practice].

PMID- 10086121
TI  - [Non-cardiac chest pain of unknown origin: prevalence and natural course].

PMID- 10086122
TI  - [Non-cardiac chest pain of unknown origin: prevalence and natural course].

PMID- 10086123
TI  - [A very severe course of psittacosis in pregnancy].

PMID- 10086124
TI  - [Mechanical complications due to ischemic damage after an acute myocardial
      infarct].
AB  - Three patients, two women aged 61 and 60 years and one man aged 78 years, who had
      sustained a myocardial infarction shortly before, developed acute dyspnoea, shock
      and (or) chest pain, and a holosystolic souffle. They suffered from rupture of
      the interventricular septum, acute mitral valve incompetence due to rupture of
      the papillary muscles, and rupture of the free wall of the ventricle, and died in
      spite of attempts at surgical repair. In these relatively infrequent mechanical
      complications of myocardial infarction the interval between the initial
      myocardial infarction and the onset of dyspnoea or profound shock is
      characteristic. With the current thrombolytic therapy and beta-blockade,
      reduction of the mechanical complications of myocardial infarction is possible,
      in particular of rupture of the free wall of the ventricle.

PMID- 10086125
TI  - [Lung damage due to mechanical ventilation].
AB  - Mechanical ventilation in both children and adults is still associated with
      development of lung injury, both short term and long term. In particular,
      ventilation with high tidal volumes and low positive end-expiratory pressures
      (PEEP) contributes significantly to development of lung injury. Suggested
      preventive measures consist of limiting peak inflation pressures, preventing high
      tidal volumes, and applying high PEEP to prevent alveolar collapse. Recent
      studies have demonstrated that mechanical ventilation, via stretch of lung
      tissue, results in an inflammatory reaction in the lungs. This is known as
      biotrauma. The degree of inflammation depends on the ventilator settings and mode
      of ventilation. This inflammatory reaction may not be limited to the lungs but,
      via inflammatory mediators, may cause multiple organ dysfunction as well. Future
      research needs to be concentrated on how to modify this ventilator induced
      inflammatory reaction in order to prevent lung injury as well as systemic injury.

PMID- 10086126
TI  - [The place of long-acting beta 2 adrenergic agonists in the treatment of asthma
      and chronic obstructive lung disease (COPD)].
AB  - At the introduction of long-acting beta 2-adrenergic agonists physicians were
      reluctant to prescribe them for prolonged use, as they might increase mortality
      due to asthma. In national and international guidelines beta 2-agonists are
      reserved for moderate to severe asthma. Well-controlled studies have shown,
      however, that long-acting beta 2-agonists are effective bronchodilators, able to
      improve symptoms and lung function and to decrease the number of exacerbations.
      As long as these bronchodilators are combined with inhaled steroids, they may be
      beneficial in early stages of asthma of low severity. In the treatment of COPD
      the place of long-acting beta 2-agonists is not clear yet. First experiences
      show, however, that these drugs deserve a place in the treatment of COPD, notably
      against nocturnal dyspnoea. Use of long-acting beta 2-agonists is often
      associated with clear improvement in quality of life and walking distance of COPD
      patients, which does not appear to be accompanied by distinct improvement in
      pulmonary function (FEV1), however.

PMID- 10086127
TI  - [A series of articles on the usefulness and uselessness of physical diagnostics;
      comment].
AB  - The sensitivity, specificity and reproducibility (especially the interassessor
      variation) of many physical diagnostic tests taught in the medical curricula
      appear not to have been established. Nevertheless, many of these tests are
      mentioned as end terms in the General plan 1994 medical education. A series of
      articles in this journal will be concerned with tests from physical diagnostics,
      with reference to usefulness and uselessness: sensitivity, specificity and
      reproducibility.

PMID- 10086128
TI  - [Physical diagnosis--plantar reflex].
AB  - On stimulation of the plantar surface an extensor response of the toes
      (especially the big toe; Babinski sign) indicates a disorder of the corticospinal
      system: disinhibition of reflex activity causes the big toe to be recruited into
      the synergistic flexion reflex of the leg (toe extensors are flexors in a
      physiological sense). Proper assessment of the plantar reflex therefore involves
      not only rating toe movements, but also observing simultaneous contraction of
      flexor muscles in the thigh. Disregard of the association with the flexion
      synergy has given rise to some misunderstandings.

PMID- 10086129
TI  - [Abstention: arguments for stopping or withholding of life-sustaining treatment.
      Task Force Ethics, Philosophy and History of Medicine, Catholic University].
AB  - A decision to withhold or withdraw life-sustaining treatment can only be
      justified if one (or more) of three arguments apply: (a) the patient refuses the
      treatment concerned, (b) the therapy cannot produce the intended medical effect,
      or (c) the therapy may be effective, but the effects are not meaningful.
      Assessment of effectiveness is a medical professional judgement. This assessment
      should take into account the proportionality of medical (technological) means and
      ends. Treatment is meaningful if (a) it serves a reasonable purpose for the
      patient, and (b) the benefits outweigh the burdens for the patient. The patient's
      own view determines the meaningfulness of treatment. Physicians should talk with
      patients about the meaningfulness of life-sustaining treatment while there is
      time, to avoid the situation that such questions come up just when a patient has
      lost his capacity to communicate. In case a patient is incompetent, physicians
      should try to infer from previous utterances of the patient what he or she would
      have wished in this situation. If it is impossible to reconstruct the patient's
      view, there is no basis for withdrawing or withholding medically effective life
      sustaining treatment.

PMID- 10086130
TI  - [Findings in children with psoriasis].
AB  - OBJECTIVE: To describe the clinical characteristics and treatments of children
      with psoriasis. DESIGN: Retrospective, descriptive. METHODS: The medical records
      were studied of all 38 children with psoriasis who visited the outpatient clinic
      for Dermatology of the University Hospital/Wilhelmina Children's Hospital
      Utrecht, the Netherlands, for the first time between 1 January 1995 and 31
      December 1997. RESULTS: The 38 children accounted for 3.6% of all children in
      whom a diagnosis was made. There were 19 boys and 19 girls. 79% had psoriasis
      vulgaris and 11% psoriasis guttata. Average age of onset was 6.8 years for girls
      and 9.3 years for boys. Family history was positive in 42%. The limbs were
      affected most. Nail changes were seen in 11%. Provoking factors were stress,
      infections, summertime and injuries of the skin. In almost all patients in the
      outpatient department local mono- and/or combination therapy of corticosteroids
      in cream or ointment with salicylic acid and tar was given.

PMID- 10086131
TI  - [Perinatal mortality in Delft and surrounds, 1983-1992: further reduction is
      possible by targeting lethal congenital abnormalities and placental
      insufficiency].
AB  - OBJECTIVE: To establish the distribution of perinatal mortality over the various
      levels of obstetrical care, taking into account the various causes of perinatal
      mortality. DESIGN: Prospective, descriptive. METHODS: Data were collected on all
      parturitions of women living in the region Delft-Westland-Oostland (DWO), the
      Netherlands, during the period 1983-1992, regardless of the ultimate setting of
      the parturition. A prospective regional registration system for perinatal
      mortality in the region was matched with the registration by the Central
      Statistics Office (CBS). With anonymous linking, duplicatures could be excluded.
      The causes of death were assessed by a gynaecologist, a paediatrician and a child
      pathologist. It was determined for all cases of perinatal mortality whether the
      antenatal care had been under the final responsibility of a midwife or a general
      practitioner (primary care), either at home or in the outpatient clinic, or under
      the final responsibility of a gynaecologist (secondary care). RESULTS: In the
      decade studied, 28,983 children were born in the DWO region; 51% under primary
      care management. The actual perinatal mortality of the region was calculated as
      amounting to at least 247 cases (0.85%). In 26% (n = 64) of these, the childbirth
      was managed under primary care responsibility, in 43% (n = 106) after risk
      selection from primary to secondary care, in 14% (n = 34) under the exclusive
      responsibility of secondary care and in 17% (n = 43) after risk selection from
      secondary to tertiary care. The most frequent causes of death were progressive
      placental insufficiency and lethal congenital anomalies. CONCLUSIONS: The results
      show that further decrease of perinatal mortality may be achieved by risk
      selection (in primary care) with regard to lethal congenital anomalies and acute
      or progressive placental abnormalities. The perinatal mortality is so low (0.85%)
      that further medicalization of childbirth may be expected to contribute only
      little to a further decrease of the perinatal mortality figures.

PMID- 10086132
TI  - [The percentage of articles which were accepted or rejected for publication in
      the Dutch Journal of Medicine in 1997].
AB  - OBJECTIVE: To determine the acceptance and rejection percentages of articles
      submitted to the editors of the Nederlands Tijdschrift voor Geneeskunde (NTvG) in
      1997. DESIGN: Retrospective. METHOD: The data on all articles reviewed by the
      editors of the NTvG in 1997 were extracted from the registration system in April
      1998. These included the outcome of the review process (rejection or acceptance
      for publication or no definite decision yet), the article category (e.g.,
      original article, review article), and whether the article had been solicited by
      the editors or was a spontaneous submission. RESULTS: In 1997, 845 articles were
      received. Of these 28% (240) were rejected and 59% (497) were accepted for
      publication. On 13% (108) no decision had been made (in April 1998). Of the
      articles decided upon 36% were rejected (extrapolated). 705/845 (83%) articles
      were unsolicited: of these 33% (235) were rejected and 54% (382) accepted; on 13%
      (88) the decision was pending. The solicited articles numbered 140 (17%); of
      these 4% (5) were rejected and 82% (115) were accepted; on 14% (20) no decision
      had been made yet. CONCLUSION: The rejection of articles submitted to NTvG in
      1997 was 36% (in 1990 38%). Solicited articles were rejected less frequently than
      unsolicited ones. The yearly number of articles submitted and the rejection
      percentage have not changed drastically during the last eight years.

PMID- 10086133
TI  - [Epiploic appendicitis].
AB  - A 50-year-old woman presented with sudden onset of localised pain in the right
      and later the left lower abdomen, without other complaints. Only tenderness in
      the left lower abdomen was noted at physical examination. The ESR (25 mm/1st hr)
      and C-reactive protein (25 mg/l) were slightly elevated. The ultrasound (US)
      revealed a solid ovoid non-compressible hyperechoic mass (diameter 26 mm) at the
      point of maximum tenderness. The CT scan confirmed the presence of this lesion
      which appeared to be an infarction of an epiploic appendix with subsequent
      inflammation, called primary epiploic appendagitis. On conservative therapy the
      pain resolved in four weeks. The follow-up US and CT showed disappearance of the
      lesion after 35 days. When epiploic appendagitis is suspected, an US followed by
      CT is helpful to confirm the diagnosis and to avoid unnecessary treatment with
      antibiotics or operation.

PMID- 10086134
TI  - [Memisa and home care for AIDS patients in Zambia].
AB  - Health care in Zambia has since long been receiving support from non-governmental
      organizations (NGOs) like Memisa. Church organizations bear responsibility for a
      considerable part of the national health services. During the last 15 years,
      growing attention has been given to improvement of basic services in the villages
      and to recruitment and organization of groups in the community active in the
      field of health care. The combat against AIDS is a major focus. Many NGOs give
      health education on HIV and AIDS, are coaching HIV-positive individuals and are
      trying to organize support for AIDS patients and their relatives and relief for
      women and children after the death of husband or father. The community home care
      projects established in the urban areas of Copperbelt province in Zambia provide
      a decent terminal phase for AIDS patients and assist the surviving families in
      maintaining a certain socioeconomic level of existence.

PMID- 10086135
TI  - [Results of laparoscopically assisted vaginal hysterectomies in the Ikazia
      Ziekenhuis, Rotterdam, 1993-1997].

PMID- 10086136
TI  - [Behcet's disease].
AB  - Three women aged 30, 38 and 34 years, originating from Morocco, the Dominican
      Republic and Turkey, had been suffering since several years from, among other
      things, oral aphthae, vaginal ulcers and skin lesions without specific
      abnormalities at examination of blood and biopsies. The diagnosis of Behcet's
      disease was made and immunomodulating treatment instituted, following which the
      patients improved. Behcet's disease is a chronic inflammatory multisystemic
      disorder of unknown aetiology. Originally it was characterised as a triad of
      recurrent oral aphthae, genital ulcers and inflammatory eye disease. Because
      symptoms manifest themselves over many years the disease can be missed or
      misdiagnosed easily. There is no laboratory test available to support the
      diagnosis, so that the diagnosis is based on clinical symptomatology. The
      incidence is increasing due to migration from areas with higher prevalence.

PMID- 10086137
TI  - ['Authority-based' versus 'evidence-based' blood pressure measurements in
      pregnancy].
AB  - Recent evidence suggests that the fifth Korotkoff sound (K5) is a much more
      reliable point of measurement to determine diastolic blood pressure in pregnant
      women than the fourth one (K4). The guidelines for obstetricians and midwives
      should be corrected without delay to reflect this new knowledge. In non-pregnant
      people K5 already is the point of reference.

PMID- 10086138
TI  - ['Acute abdomen' in children].
AB  - A child is said to have an 'acute abdomen' in case of severe abdominal pain of
      sudden onset. Further investigations are necessary if the pain is very bad,
      persists for longer than 3-4 hours or is accompanied by vomiting. Failure to make
      the correct diagnosis may result in severe complications. The principal cause in
      an older child is acute appendicitis. This diagnosis is to be based on the
      anamnesis, physical examination and laboratory tests. If one of these is typical,
      active observation is indicated; if two or three are typical, appendectomy is
      indicated. Differential diagnoses can only be made during laparotomy.
      Intussusception occurs more frequently in toddlers. In a child with possible
      intussusception, observation is not justified: the diagnosis should be excluded
      by a contrast colonic X-ray, or operation should be performed either immediately
      or, if the symptoms persist, after the X-ray. Rest and patience, careful and
      child-adapted approach, and correct evaluation of aberrant symptoms may minimize
      unnecessary intervention.

PMID- 10086139
TI  - [Fever of unknown origin in a young child: diagnosis and treatment].
AB  - In children with fever without focus, evaluation should be aimed at recognition
      of children with an increased risk of bacteraemia or of major bacterial
      infections, while young children in particular will show few typical symptoms of
      bacterial infections. A child younger than 1 month with fever (> or = 38.0
      degrees C) or hypothermia (< 36.0 degrees C) needs clinical evaluation and
      additional diagnostic investigations. In children aged from 1 to 36 months
      referral to hospital should be based on presence of age specific clinical
      characteristics, i.e. toxic appearance, high fever, diarrhoea, decreased urine
      production, tachypnoea, or bulging fontanelle. Presence of clinical
      characteristics as judged by a paediatrician or abnormal laboratory findings
      indicates hospitalisation and treatment with parenteral antibiotics. Absence of
      alarming clinical characteristics with normal laboratory values justifies
      outpatient follow-up without treatment or additional diagnostic procedures.
      Careful instructions to parents regarding observation, parents' ability to detect
      clinical changes and facilities for rapid medical re-evaluation are crucial.

PMID- 10086140
TI  - [Epileptic seizures in children].
AB  - There exist various types of epilepsy in children, which can be classified on the
      basis of nature and severity of the impairment of consciousness and the motor
      phenomena. The anamnesis is the main aid in distinguishing a seizure from a non
      epileptic convulsion. Convulsions may have a number of causes, which may or may
      not be acute, while several factors may provoke attacks. The extent and necessity
      of supplementary investigation depend mostly on the child's clinical condition at
      presentation and on the nature of the seizure(s). The electro-encephalogram is
      important for the classification of the type of seizure. Anti-epileptic
      medication should not be started after a single epileptic seizure; whether it
      will be started after several attacks depends on the frequency and severity of
      the seizures, and on the syndrome diagnosis made. The long-term prognosis depends
      mostly on the syndrome diagnosis.

PMID- 10086141
TI  - [Dehydration due to gastro-enteritis in children].
AB  - Gastroenteritis is the commonest cause of dehydration in children. Infants and
      young children dehydrate more easily than adults if fluid intake is insufficient
      or fluid loss too high because of the combination of a large extracellular
      volume, a large insensible loss and a mediocre concentrating capacity of the
      kidney. Fluid loss due to gastroenteritis is often accompanied by electrolyte and
      acid-base disturbances. Oral rehydration with oral rehydration salts (ORS) is
      nearly always possible. Re-evaluation after 6 hours is advised especially in
      young children. Early (< 6-24 hours) resumption of feeding is important. If
      rehydration with frequent small amounts of ORS at home fails, continuous
      nasogastric tube feeding in the hospital is a good alternative. In dehydration
      exceeding 10% of body weight intravenous rehydration is necessary.

PMID- 10086142
TI  - [Acute respiratory insufficiency in children].
AB  - Acute respiratory distress in children is often a consequence of asthma. Other
      causes are subglottic laryngitis, epiglottitis, aspiration of a foreign body,
      acute bacterial pneumonia or pneumothorax. History and physical examination
      should differentiate between the various diseases. Asthma is characterized by
      recurrent symptoms and signs, while this is not the case with the other causes of
      acute breathlessness described. An asthma exacerbation is often preceded by one
      or more prodromes. In case of aspiration of a foreign body, like a peanut,
      immediate action is needed to prevent irreversible damage to the airways.
      Subglottic laryngitis and epiglottitis are both characterized by an inspiratory
      stridor; in case of epiglottitis immediate action is needed, while in case of
      subglottic laryngitis observation time is available in most cases. Pneumothorax
      as a cause of acute breathlessness is rare in childhood; it should be considered
      in male smoking leptosomic asthmatic adolescents.

PMID- 10086143
TI  - [Secondary infection with methacillin resistant Staphylococcus aureus in Dutch
      hospitals (July 1997-June 1996].
AB  - OBJECTIVE: To study the spread of methicillin-resistant Staphylococcus aureus
      (MRSA) in hospitals, especially secondary MRSA infections in relation to the
      origin of the MRSA strain and the measures taken regarding contact isolation.
      DESIGN: Secondary data analysis. METHODS: As part of the national MRSA
      surveillance of the National Institute of Public Health and the Environment, data
      were collected using questionnaires. The analysis covered the period July 1994
      June 1996 and was performed for index cases of secondary infections versus
      sporadic cases. Possible risk factors were determined. RESULTS: In the study
      period 30 index cases of (clusters of) secondary infections and 191 sporadic
      cases were found. The size of the clusters was limited. Strict contact isolation
      as described in the guidelines of the Dutch Working Group on Infection Prevention
      prevented secondary infections in most cases. Patients for whom no relation could
      be found between the MRSA infection and a stay abroad were found to have caused
      more secondary infections, even when the data were corrected for contact
      isolation measures.

PMID- 10086144
TI  - [Priapism caused by simultaneous use of zuclopentixol and paroxetine].
AB  - A man aged 32 with psychotic and depressive symptoms was treated with
      zuclopentixol and paroxetine, following which priapism developed. After puncture
      of coagulated blood from the corpora cavernosa urine retention developed and a
      suprapubic catheter had to be introduced temporarily for urine drainage.
      Zuclopentixol is an alpha 1-receptor blocker and paroxetine inhibits the hepatic
      enzyme P450-2D6 required for conversion of the two substances. Separately, and
      especially in combination, these substances cause a disturbance of the drainage
      from the corpora cavernosa leading to ischaemia and complications such as
      dysuria, urine retention, impotence, fibrosis of the corpora cavernosa and
      gangrene. Consequently, timely treatment is indicated.

PMID- 10086145
TI  - [Alternative therapies after enactment of the Individual Health Care
      Professionals Act (Wet BIG)].
AB  - Alternative therapies, i.e. methods of treatment which cannot be considered to
      form part of the regular medical professional standard, are practised not only by
      alternative practitioners, but to some extent by qualified physicians, also. The
      Individual Health Care Professionals Act recently enacted in the Netherlands
      concerns the freedom to practise this complementary medicine. Whereas for
      physicians the decisions of the disciplinary courts will remain the determining
      factor, the new law--recognising the right and responsibility of individuals to
      seek health care wherever they wish--provides more room for alternative
      practitioners. This does not imply that the law does no longer protect the public
      from irresponsible forms of alternative medicine. However, it remains to be seen
      whether the instruments provided by the law to repress such practices are
      sufficient.

PMID- 10086146
TI  - [The ear thermometer: not a good replacement for the rectal thermometer].

PMID- 10086147
TI  - [The ear thermometer: not a good replacement for the rectal thermometer].

PMID- 10086148
TI  - [Palliative treatment of bone metastasis with bone seeking radionuclides].

PMID- 10086149
TI  - [Fever due to antithyroid agents].
AB  - Three patients, females aged 62, 67 and 32 years, were presented with fever and
      sore throat and had severe agranulocytosis (granulocyte count < 100/microliter).
      All had Graves' disease and were being treated with thiamazole 30 mg once a day.
      Thiamazole was discontinued and treatment with antibiotics initiated. None of the
      patients received granulocyte-colony stimulating factor (G-CSF). The mean
      recovery time of granulocytes was 9 days and there were no fatalities. Patients
      who receive antithyroid agents should be warned against the serious and
      potentially lethal side effect of agranulocytosis.

PMID- 10086150
TI  - [Hypertension in the Negro patient].
AB  - Essential hypertension appears to be more prevalent among blacks than among
      whites and has an earlier onset in blacks. Many data in this field come from
      studies in the African-American population. Hypertension-related complications,
      e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular
      disease, are encountered more often among blacks and frequently run a more severe
      course. Factors that might explain the racial difference in prevalence of
      hypertension and hypertensive complications include both genetic and
      environmental variables. Hypertension in blacks is characterized by salt
      sensitivity, a tendency towards expanded plasma volume and low plasma renin
      levels. Socioeconomic factors, the higher prevalence of obesity and insulin
      resistance may contribute to the high prevalence of hypertension in blacks.
      Aggressive antihypertensive therapy appears mandatory in the black hypertensive,
      possibly with lower goal blood pressures than the 140/90 mmHg generally
      recommended. Diuretic monotherapy proves to be the first-line therapy, calcium
      channel blockers are an attractive alternative. Black patients are frequently
      less responsive to monotherapy with angiotensin-converting enzyme (ACE)
      inhibitors and beta-blocking agents. This black/white difference in therapeutic
      response can, however, be eliminated by addition of a diuretic.

PMID- 10086151
TI  - [Drug therapy in Parkinson's disease].
AB  - Levodopa is still the mainstay of the treatment of Parkinson's disease.
      Limitations of levodopa therapy have led to development of numerous therapeutic
      approaches at the level of levodopa/dopamine metabolism, dopamine receptors,
      dopamine transporter, and other neurotransmitter systems. New insights into the
      pathophysiology of Parkinson's disease have led to the promising concepts of
      neuroprotection and neurorestoration. In daily practice therapeutic management of
      Parkinson's disease is still symptomatic.

PMID- 10086152
TI  - [Clinical thinking and decision-making in the practice. A young man in shock].
AB  - A previously healthy male aged 32 years with noticeably long extremities went
      into shock whilst straining to defaecate. He did not lose consciousness and
      reported pain high in the back and in the abdomen. Transoesophageal
      echocardiography revealed no abnormalities. Ultrasonography of the abdomen showed
      blood in the abdominal cavity, following which laparotomy was performed. An
      aneurysm of the splenic artery was found to have ruptured. The aneurysm and the
      spleen were removed. Morbid-anatomical examination showed no vascular
      abnormalities. The postoperative course was uneventful.

PMID- 10086153
TI  - [No adverse effects on intelligence 6 years after surgery for epilepsy].
AB  - OBJECTIVE: To evaluate the long-term effects of epilepsy surgery on intelligence.
      DESIGN: Prospective descriptive. METHOD: The group included 20 patients of the
      Instituut voor Epilepsiebestrijding, Heemstede, and the Epilepsiecentrum
      Kempenhaeghe, Heeze, the Netherlands, who suffered from medication-resistant
      epilepsy originating from the temporal lobe, in 9 patients from the left lobe
      (mean age: 33.1 years), in 11 from the right one (34.6 years). The epilepsy focus
      was removed surgically (Academic Hospital, Utrecht). The scores on the 'Wechsler
      adult intelligence scale' (WAIS) were determined before the operation and 6
      months, 2 years and 6 years after operation. RESULTS: The mean WAIS IQs before
      operation were: verbal IQ (VIQ): 111.8 and performance IQ (PIQ): 117.7 in the
      group treated on the left and VIQ: 113.5 and PIQ: 112.4 in the group treated on
      the right. The mean gains 6 years after operation were 0.8 and 2.6 VIQ-points and
      8.7 and 8.5 PIQ-points respectively. In the patients operated on the left the
      difference between VIQ and PIQ was significant 2 and 6 years after operation. The
      increase in IQs remained within what could be expected in retests. Only for the
      VIQ of patients treated on the left was a smaller retest effect found.
      CONCLUSION: These figures show that in the long term epilepsy surgery does not
      have an adverse outcome on the intelligence.

PMID- 10086154
TI  - [Pleural empyema in mechanically ventilated patients with pneumonia].
AB  - Two males aged 41 and 32 years developed pneumonia which responded inadequately
      to antibiotic treatment and necessitated mechanical ventilation. It was only
      after surgical and digital opening, drainage of pus pockets and daily pleural
      lavage that the clinical picture improved. The microorganisms cultured from both
      patients included Streptococcus milleri, probably acquired by aspiration.
      Thoracic empyema as a complication of pneumonia is clinically recognised by lack
      of response to antimicrobial agents. For the diagnosis, ultrasonographic and CT
      imaging, followed by pleural puncture are used. Simple parapneumonic effusions
      are managed by drainage with or without rinsing with normal saline, while in
      advanced empyema, instillations with fibrinolytic agents have proved safe and
      effective. Sometimes, video-assisted thoracoscopic or conventional surgery is
      necessary to clear the pleural space, while in complicated cases, extensive
      surgical procedures are warranted.

PMID- 10086155
TI  - [Memisa in Afganistan: reconstruction of primary health care in a country during
      civil war and with restricted freedom of movement for women].
AB  - Afghanistan has the number five position in the world with regard to child
      mortality and ranks number two with regard to child mortality and ranks number
      two with regard to maternal death. Towards the end of 1994 Memisa agreed to
      assist IbnSina, an Afghan non-governmental organization which had been asked to
      rehabilitate basic health services in 4 regions via their existing immunization
      programme. After the withdrawal of the Russian army, the country is being torn
      apart by fighting bands of extremists. The rapid and successful rise of the
      Taliban, a movement of armed islamic fundamentalist students, puts severe
      restrictions on public life and on the rights of women, and makes it even more
      difficult to set up a health care system which is equally accessible to men and
      women. IbnSina-Memisa strives to revive health care in 4 regions and to cope with
      the logistic and cultural constraints which have to be faced.

PMID- 10086156
TI  - [Convulsions during prophylactic use of mefloquine].

PMID- 10086157
TI  - [Hyperammonemia in hydronephrosis].

PMID- 10086158
TI  - [Pilomatrixoma often not identified as such].

PMID- 10086159
TI  - [Four new drugs for glaucoma: apraclonidine, brimonidine, dorzolamide and
      latanoprost].

PMID- 10086160
TI  - [Addisonian crisis precipitated by levothyroxine replacement therapy].

PMID- 10086161
TI  - [Benign paroxysmal positional vertigo].

PMID- 10086162
TI  - Adolescent development: setting the stage for influencing health behaviors.
AB  - Adolescent development is viewed as the overarching framework for approaching
      disease prevention and health promotion. This chapter is a review of salient
      developmental issues in adolescence, identification of the potential effects of
      adolescent development on health behaviors, identification of conceptual and
      theoretical frameworks to address the behaviors, and suggestions for the timing
      and tailoring of interventions to prevent health risk behaviors and promote
      health.

PMID- 10086163
TI  - The psychological basis of health promotion for adolescents.
AB  - Temporal trends in adolescent morbidity and mortality and the psychological
      factors that underlie adolescents' risk-taking behavior are reviewed in this
      chapter. Theoretical models useful for understanding risk-taking behavior and
      developing effective preventive interventions are described. Finally,
      intervention strategies, both on individual and community level, are identified
      that may enhance adolescent health promotion efforts.

PMID- 10086164
TI  - How legislation and health systems can promote adolescent health.
AB  - This chapter focuses on some of the laws and regulations that could make it
      easier for adolescents to adopt health-promoting and disease-preventing
      behaviors, or that have minimized the dangers that might be caused by their
      behaviors. It also reviews some of the aspects of health care systems that may
      present barriers to health-promoting behaviors and suggests how they might be
      changed.

PMID- 10086165
TI  - The social environments of adolescents: associations between socioenvironmental
      factors and health behaviors during adolescence.
AB  - The social worlds of the adolescent and their potential effect on health behavior
      are the focus of this chapter. Social cognitive theory, resiliency theories, and
      the theoretical implications of focusing on lifestyle patterns of adolescents are
      discussed in order to provide a theoretical frame of reference for viewing the
      complex interactions between individual factors, socioenvironmental factors, and
      health-related behaviors among adolescents. Factors within the different social
      environments (family, school, peers, and community) are discussed and some
      general recommendations based upon empirical research findings and theories about
      adolescent health behavior are made.

PMID- 10086166
TI  - Cross-cultural issues in prevention, health promotion, and risk reduction in
      adolescence.
AB  - The important roles that culture, race, and poverty play in contributing to
      health beliefs and health behaviors are reviewed in this chapter. It also
      outlines strategies for working with young people, their parents, and their
      communities in order to deliver "culturally effective" health care services, with
      an emphasis on prevention, health promotion, and risk reduction.

PMID- 10086167
TI  - Adolescent health assessment and promotion in office and school settings.
AB  - Issues of health assessment and health promotion for adolescents have received
      increased attention during the past decade with the publication of several
      national and international guidelines for health assessment and a more intense
      examination of "what works and what doesn't work" in the area of health
      promotion. In this chapter, history and definitions of adolescent health
      assessment are reviewed, a synopsis of currently available office guidelines is
      provided, data regarding health screening and promotion in clinical practice are
      presented, and issues of health screening and education in school settings are
      discussed.

PMID- 10086168
TI  - Sexually transmitted diseases, unintended pregnancy, and adolescent health
      promotion.
AB  - Adolescence is a critical period in the development of sexual behaviors that may
      lead to acquiring sexually transmitted diseases (STDs), including human
      immunodeficiency virus (HIV), and to unintended pregnancy. Understanding
      adolescent sexual behavior is essential for understanding adolescents' risk of
      pregnancy and STD/HIV infection and for planning and evaluating health promotion
      activities. This chapter reviews the sexual behaviors and psychosocial factors
      associated with STDs and unintended pregnancy among adolescents as well as school
      , community-, and clinic-based interventions designed to reduce risk behaviors
      and promote adolescent sexual health.

PMID- 10086169
TI  - Promoting healthy eating and physical activity in adolescents.
AB  - The purpose of this article is to provide an update on promoting healthy dietary
      and physical activity behaviors in adolescents. In the first part of the article
      the authors discuss the importance of healthy eating and physical activity during
      adolescence, present national recommendations and guidelines for diet and
      activity, and briefly review major nutrition and physical activity concerns of
      adolescents today. The second part presents a review of diet- and activity
      related health promotion and risk reduction factors in a variety of settings and
      provides recommendations for practitioners. Future research needs are also
      addressed.

PMID- 10086170
TI  - Injuries and violence: risk factors and opportunities for prevention during
      adolescence.
AB  - More adolescent in the United States die from injuries than from any other cause.
      This chapter describes the three leading causes of death among adolescents
      interpersonal violence, suicide, and motor vehicle-related injuries. The authors
      examine risks associated with alcohol use and access to firearms as well as
      injuries that occur at work and while playing sports, and end with
      recommendations for preventing adolescent injuries for health care providers,
      schools and communities.

PMID- 10086171
TI  - Long-term consequences of adolescent health behaviors: implications for
      adolescent health services.
AB  - The authors discuss the evidence supporting the effectiveness of adolescent
      preventive services to influence health outcomes, the magnitude of the long-term
      consequences of adolescent health-compromising behaviors, and their implications
      for health policies. Particular attention is given to the contribution that
      behaviors participated in or begun during adolescence have on long-term health,
      including cancer and heart disease. They postulate the health benefits that might
      accrue from the widespread implementation of comprehensive adolescent preventive
      services, assuming a conservative estimate of effectiveness, could be
      significant.

PMID- 10086172
TI  - Adolescent tobacco, alcohol, and drug use: current findings.
AB  - The authors provide assessment of prevalence of adolescent substance use, along
      with a description of risk and protective factors and process-oriented conceptual
      approach to prevention of substance use among teens. They present selected
      adolescent substance use prevention programs and results from evaluation studies.
      Limitations of existing prevention programs and suggestions for future prevention
      efforts are also discussed.

PMID- 10086173
TI  - Progress in adolescent mental health.
AB  - This chapter reviews the status of emotional and behavioral problems in
      adolescents and current issues in their assessment and treatment. The authors
      emphasize the need for the development of mental health programs for adolescents
      in natural settings such as schools, and present a conceptual framework for
      intervention based on provider knowledge of risk and protective factors.

PMID- 10086174
TI  - Red blood cell enzymes and their clinical application.
AB  - Red blood cell enzyme activities are measured mainly to diagnose hereditary
      nonspherocytic hemolytic anemia associated with enzyme anomalies. At least 15
      enzyme anomalies associated with hereditary hemolytic anemia have been reported.
      Some nonhematologic disease can also be diagnosed by the measurement of red blood
      cell enzyme activities in the case in which enzymes of red blood cells and the
      other organs are under the same genetic control. Progress in molecular biology
      has provided a new perspective. Techniques such as the polymerase chain reaction
      and single-strand conformation polymorphism analysis have greatly facilitated the
      molecular analysis of erythroenzymopathies. These studies have clarified the
      correlation between the functional and structural abnormalities of the variant
      enzymes. In general, the mutations that induce an alteration of substrate binding
      site and/or enzyme instability might result in markedly altered enzyme properties
      and severe clinical symptoms.

PMID- 10086175
TI  - Endogenous mediators in sepsis and septic shock.

PMID- 10086176
TI  - Current concepts of coagulation and fibrinolysis.

PMID- 10086177
TI  - Tumor markers: reclassification and new approaches to evaluation.

PMID- 10086178
TI  - Branched DNA signal amplification for direct quantitation of nucleic acid
      sequences in clinical specimens.
AB  - In this chapter I have reviewed the development of bDNA as a method for
      quantitation of nucleic acid targets and the application of this technology to
      the study of infectious diseases and cell biology. The ability to quantify viral
      nucleic acids in clinical specimens has led to a better understanding of the
      pathogenesis of chronic viral infections such as HIV-1, HCV, and HBV. The
      information provided by these methods can also be important in the management of
      patients with these infections. The prognostic value of a single baseline HIV-1
      RNA level rivals that surgical staging procedures for cancer, which are among the
      most powerfully predictive tests in medicine (Mellors et al., 1996). These
      methods have been used to assess rapidly the effects of antiviral therapy, which
      has both expedited the development of antiviral drugs and improved the management
      of patients with HIV-1 and HCV infections. bDNA has several characteristics that
      distinguish it from the quantitative target amplification systems, including
      better tolerance of target sequence variability, more direct measurement of
      target, simpler sample preparation, and less sample-to-sample variation. However,
      the first- and second-generation bDNA assays lacked sensitivity compared with the
      target amplifications systems. The changes incorporated into the third-generation
      assays have effectively increased the signal-to-noise ratio to such a high level
      that the analytical sensitivity of system 8 bDNA approaches that of PCR. In
      theory, bDNA can be made even more sensitive by increasing both the sample volume
      and the signal-to-noise ratio. Nonspecific hybridization can be further reduced
      by finding more effective blockers for the solid phase or by redesigning the
      amplifier molecule or the solid phase itself. The increased sensitivity may
      create new applications for the technology in filter and in situ hybridization
      assays.

PMID- 10086179
TI  - Mammalian 15-lipoxygenases. Enzymatic properties and biological implications.

PMID- 10086180
TI  - Molecular cloning of a second human 15S-lipoxygenase and its murine homologue, an
      8S-lipoxygenase. Their relationship to other mammalian lipoxygenases.

PMID- 10086181
TI  - Arachidonate 12-lipoxygenase isozymes.

PMID- 10086182
TI  - Expression of leukocyte-type 12-lipoxygenase and reticulocyte-type 15
      lipoxygenase in rabbits.
AB  - From a rabbit reticulocyte library a full length cDNA was isolated which
      predicted a novel lipoxygenase (LOX) sharing 99% identical amino acids with the
      rabbit 15-lipoxygenase. HPLC product analysis of the bacterially expressed
      protein identified it as a leukocyte-type 12-lipoxygenase (1.12-LOX). This proves
      the co-expression of a 15-lipoxygenase and a 1.12-lipoxygenase in one mammalian
      species. Among the six amino acids that are different to rabbit 15-lipoxygenase,
      leucine 353 is shown to be the primary determinant for 12-positional specificity.
      In the 3'-untranslated region of the 12-LOX-mRNA a CU-rich, 20-fold repetitive
      element has been found, closely related to the differentiation control element
      (DICE) of the rabbit 15-LOX-mRNA which is organized by ten repeats of 19 bases.
      By genomic PCR the 3'-terminal part of the gene for the novel 12-lipoxygenase
      containing the introns 10-13 has been amplified and sequenced. The introns were
      very similar in length to the corresponding 15-lipoxygenase introns with 89% to
      95% identical nucleotide sequences. By screening a rabbit reticulocyte library an
      alternative 15-lipoxygenase transcript of 3.6 kb has been detected containing a
      1019 nucleotides longer 3'-untranslated region (UTR2) than the main 2.6 kb mRNA.
      The determination of the tissue distribution by Northern blotting showed that the
      3.6 kb mRNA2 was only expressed in non-erythroid tissues, whereas the 2.6 kb
      mRNA1 was exclusively expressed in reticulocytes. The only cell type which has
      been found to express the 1.12-lipoxygenase abundantly are monocytes. The results
      indicate that the expression of 1.12-lipoxygenase and 15-lipoxygenase is highly
      regulated. The UTR2 of the 15-LOX-mRNA2 contained a novel eight-fold repetitive
      CU-rich motif of 23 bases length which is related but not identical to the DICE
      of 19 bases in the UTR1. The analysis of a genomic recombinant of the complete
      9.0 kb Alox15 gene confirmed that UTR1 and UTR2 are not interrupted by an
      additional intron.

PMID- 10086183
TI  - Lipoxygenase gene disruption studies. Status and applications.

PMID- 10086184
TI  - The release of polyunsaturated fatty acids and their lipoxygenation in the brain.
AB  - Stimulation of neuronal tissues with neurotransmitters results in the release of
      the polyunsaturated fatty acids 20:4n6 and 22:6n3. Astroglial cells hydrolyze
      20:4n6 and 22:6n3 equally well under both stimulated and basal conditions.
      Despite the high abundance of 22:6n3 in neuronal membranes, 20:4n6 is
      preferentially hydrolyzed from neuronal cells. These results suggest that 22:6n3
      may be of more physiological importance in neuronal membranes as a membrane
      component rather than as a released free fatty acid while in astroglia, release
      of 22:6n3 may also be a significant step involved in receptor-stimulated
      signaling processes. Oxygenation of these polyunsaturated fatty acids occurs in
      the brain. However, in contrast to the prevailing belief, lipid peroxidation
      rather than lipoxygenation is primarily responsible for their formation. In
      rodent brains, any significant lipoxygenation appears to occur only in the
      pineal. The production of hydroxylated polyunsaturated fatty acids in pineal may
      play a role in the pineal function especially in relation to melatonin synthesis.

PMID- 10086185
TI  - Biological relevance of the 12-lipoxygenase pathway for platelet and lymphocyte
      functions.

PMID- 10086186
TI  - Effect of 15-HETE on the 5-lipoxygenase pathway in neutrophils. Genuine inhibitor
      or alternative substrate?

PMID- 10086187
TI  - Adenosine. An endogenous inhibitor of arachidonic acid release and leukotriene
      biosynthesis in human neutrophils.
AB  - Insufficient arachidonic acid availability limits the biosynthesis of leukotriene
      B2 (LTB4) in polymorphonuclear leukocytes (PMN) stimulated with soluble agonists.
      We report that endogenous adenosine (Ado) present in human PMN suspensions
      suppresses LTB4 biosynthesis induced by platelet-activating factor (PAF). The
      blockade of the effects of Ado with an antagonist, theophylline, during the
      incubation of PMN resulted in significant enhancement of arachidonic acid release
      and LTB4 biosynthesis upon PAF stimulation. The enhancement of LTB4 biosynthesis
      in theophylline-treated PMN was reversed upon addition of exogenous Ado and
      analogues of Ado; 5'(N-ethyl)caboxamidoadenosine (IC50 = 6 nM) was more potent
      than Ado (IC50 = 60 nM) which was more potent than N6-cyclopentyladenosine (IC50
      = 330 nM) in inhibiting LTB4 biosynthesis, a pharmacological profile which is
      consistent with the involvement of the Ado A2 receptor type. The mechanism of
      inhibition of arachidonic acid release by Ado was investigated. Immunoblot
      analysis of cytosolic phospholipase A2 (cPLA2) in PMN fractions demonstrated that
      theophylline failed to further increase the translocation of the enzyme to
      particulate fractions (12,000 x g and 180,000 x g pellets) upon PAF stimulation.
      Moreover, the stimulation of intact PMN with PAF caused a decreased
      electrophoretic mobility of the cPLA2 and the presence of theophylline did not
      alter this mobility shift. Together, these results demonstrate that elevated
      endogenous Ado, acting through A2 receptors, suppresses arachidonic acid release
      and LTB4 biosynthesis induced by PAF. These data provide an explanation for the
      relative inability of soluble agonists to trigger leukotriene biosynthesis in
      human PMN suspensions and support the concept that Ado, by suppressing PMN
      functions, acts as a physiological anti-inflammatory agent.

PMID- 10086188
TI  - Pharmacological aspects of 5-lipoxygenase inhibition.

PMID- 10086189
TI  - The hepoxilins. A review.
AB  - This manuscript reviews the literature on hepoxilins to date. It affords a review
      of the structures, nomenclature, biosynthesis, catabolism and biological actions
      of the hepoxilins and some of their chemical analogs. Some unpublished data are
      also presented. The primary biological action of the hepoxilins appears to relate
      to their ability to release calcium from intracellular stores through a receptor
      mediated action. The receptor is intracellular, and appears to be G-protein
      coupled. The conversion of hepoxilin into its omega-hydroxy catabolite has
      recently been demonstrated through the action of an omega-hydroxylase. This
      enzyme is different from that which oxidizes leukotriene B4, as the former
      activity is lost when the cell is disrupted, while leukotriene B4-catabolic
      activity is recovered in both the intact and disrupted cell. Additionally,
      hepoxilin catabolism is inhibited by CCCP, a mitochondrial uncoupler, while
      leukotriene catabolism is unaffected. As hepoxilins cause the translocation of
      calcium from intracellular stores in the endoplasmic reticulum to the
      mitochondria, it is speculated that hepoxilin omega-oxidation takes place in the
      mitochondria, and the omega-oxidation product facilitates accumulation of the
      elevated cytosolic calcium by the mitochondria. The biological activity of stable
      analogs of the hepoxilins is also described which inhibit the calcium-releasing
      actions of neutrophil inflammatory mediators.

PMID- 10086190
TI  - Aspirin-triggered 15-epi-lipoxin A4 and stable analogs on lipoxin A4 are potent
      inhibitors of acute inflammation. Receptors and pathways.

PMID- 10086191
TI  - Modulation of LTB4 receptor in T-lymphocytes by lipoxin A4 (LXA4) and its role in
      delayed-type hypersensitivity.

PMID- 10086192
TI  - Receptors for cysteinyl-leukotrienes in human cells.

PMID- 10086193
TI  - Cysteinyl-leukotrienes and the human lung.

PMID- 10086194
TI  - 12(S)-HETE in cancer metastasis.

PMID- 10086195
TI  - A 12(S)-HETE receptor in Lewis lung carcinoma cells.

PMID- 10086196
TI  - Fatty acids, eicosanoids, and hypolipidemic agents regulate gene expression
      through direct binding to peroxisome proliferator-activated receptors.

PMID- 10086197
TI  - Biogenesis and biological function of marine algal oxylipins.
AB  - The biogenetic source of most marine algal oxylipins, which are many and of
      diverse structure, can logically be unified through a common lipoxygenase-derived
      hydroperoxide to epoxy allylic carbocation transformation. The biological role of
      oxylipins in algae remains an enigma, although numerous ideas have been put
      forth. Herein, we hypothesize and provide some evidence for an osmoregulatory
      role for these metabolites.

PMID- 10086198
TI  - Mortality and cancer incidence in biomedical laboratory personnel in Sweden.
AB  - BACKGROUND: The work in biomedical laboratories is associated with exposure to a
      mixture of known and potential chemical carcinogens, mutagens, and teratogens.
      Previous studies have suggested an excess of brain tumors and hematopoietic
      system malignancies as well as breast cancers in women. METHODS: This
      retrospective cohort study investigated the standardized mortality ratio (SMR)
      and the standardized incidence ratio (SIR) for cancer in biomedical research
      laboratory personnel in Swedish universities 1970-1992. The cohort comprised
      5,035 laboratory and, as an internal reference group, 2,923 nonlaboratory
      employees. RESULTS: The overall death rate was lower in both groups than in the
      general population. The SIR for brain tumors among male laboratory workers was
      1.69 (0.62-3.68) and among male laboratory scientists, after more than 10 years
      of work (4 cases), it was 3.11 (0.85-7.56). There was an elevated SIR for
      malignant melanoma among female scientists in laboratories (3.51, 0.96-8.98) and
      for male scientists in nonlaboratory departments (2.86, 1.05-6.22). The SIR for
      breast cancer among female laboratory scientists was 1.62 (0.78-2.98).
      CONCLUSIONS: The present findings lend some support to an excess of brain tumors
      among male scientists and of breast cancer in female scientists in biomedical
      research laboratories.

PMID- 10086199
TI  - Respiratory protective devices: rates of medical clearance and causes for work
      restrictions.
AB  - BACKGROUND: There are no published data on the outcomes and benefits of medical
      evaluations for the use of respiratory protective devices. We, therefore,
      conducted a retrospective database and chart review to assess the rates of
      medical clearance and causes for work restrictions at a Department of Energy
      complex. METHODS: All workers with work restrictions or denied clearance over a
      one-year period were identified and their medical records abstracted. RESULTS: Of
      the 5,569 workers who received medical evaluation, only 71 (1.3%) received
      limitations on respirator use documented in their medical record. Of the 65
      workers with sufficient medical records for additional analysis, 9 of the 5,569
      workers (0.2%) were denied medical clearance, while 56 workers (1.1%) received
      work restrictions. Pregnancy was the most common cause for denying medical
      clearance for respirator use. Lung disease, cardiovascular disease, and
      claustrophobia were the most common causes for work restrictions. Physical
      examination and spirometry added little to the detection of relevant medical
      conditions. CONCLUSIONS: We conclude that few workers fail medical clearance for
      respirator use or receive work restrictions. Data on adverse events from
      respirator use are needed to help design appropriate medical evaluations and
      uniform criteria for work restrictions or denial of medical clearance.

PMID- 10086200
TI  - Medical clearance for respirator use: sensitivity and specificity of a
      questionnaire.
AB  - BACKGROUND: OSHA regulations require that workers receive medical clearance prior
      to respirator use, and recently, a detailed questionnaire has been provided to
      assist with this purpose. However, there are limited published data on the
      sensitivity and specificity of self-administered questionnaires for identifying
      individuals who may safely wear a respirator. METHODS: We tested 474 consecutive
      workers at a Department of Energy complex. After completing the self-administered
      questionnaire, all workers received a standardized physician evaluation including
      interview, physical examination, and spirometry. The outcomes of the
      questionnaire assessment were compared to the outcomes of physician evaluation.
      RESULTS: Data for analysis were available from 413 of workers (87%). All workers
      received medical clearance; only 10 workers (2.4%) received work restrictions.
      The questionnaire demonstrated 100% sensitivity in identifying workers who
      required work restrictions, but had specificity of only 19%. Compared to
      physician evaluation, the questionnaire had modest sensitivity to the detection
      of chronic medical conditions. CONCLUSIONS: These data suggest that the rates of
      medical clearance for respirator use are very high, and that a self-administered
      questionnaire may be appropriate for medical clearance in certain settings. It is
      recommended that the policy of routine physician evaluation and spirometry for
      respirator clearance be re-examined.

PMID- 10086201
TI  - Inferences on the kinetics of asbestos deposition and clearance among chrysotile
      miners and millers.
AB  - BACKGROUND: The health effects of asbestos are intimately related to the fate of
      inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied
      primarily in rodents. The objective of this study was to explore the application
      of these kinetic models to human autopsy data. METHODS: We analyzed the asbestos
      fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49
      control subjects using analytical transmission electron microscopy. Statistical
      methods included standard multivariate linear regression and locally weighted
      regression methods. RESULTS: The lung burdens of asbestos bodies and chrysotile
      and tremolite fibers were correlated, as were the concentrations of short,
      medium, and long fibers of each asbestos variety. There were significant
      associations between the duration of occupational exposure and the burdens of
      chrysotile and tremolite. The concentration of chrysotile decreased with the time
      since last exposure but the concentration of tremolite did not. The clearance
      rate varied inversely with the length of chrysotile fibers. For fibers greater
      than 10 mu in length the clearance half-time was estimated to be 8 years.
      CONCLUSIONS: The patterns in our data are compatible with both of the hypotheses
      suggested from rodent experiments; the existence of a long-term sequestration
      compartment and overload of clearance mechanisms in this compartment.

PMID- 10086202
TI  - Latex allergy in Polish nurses.
AB  - BACKGROUND: Reports on the studies conducted in Western Europe and North America
      revealed that from 2.8 to 16.9% of the health care personnel were allergic to
      latex. No respective data are available from Eastern European countries. METHODS:
      A postal questionnaire inquiring about the history of latex-induced allergic
      reactions was distributed among 3,750 nurses. The participation rate was 77.3%.
      To verify the results of the survey, in randomly selected nurses, skin prick
      tests with latex and tropical fruit allergens, evaluation of total IgE, and
      specific anti-latex IgE, skin and nasal provocation with latex were performed.
      RESULTS: Allergic symptoms in the workplace were reported by 1,016 subjects
      (35%); out of this group 847 (29.2%) persons associated the symptoms with latex
      exposure. The group of cases with self-reported latex allergy revealed a
      significantly increased frequency of history of atopy, allergy to beta-lactam
      antibiotics and tropical fruits. Allergy to latex was confirmed in 33.3% of
      randomly selected nurses with a positive history of occupational allergy. It was
      found that 18.6% of nurses working at hospital wards were allergic to latex. The
      95% CI was estimated to be 13.5-23.6%. CONCLUSIONS: Latex allergy is an important
      health problem among nurses in Poland. Atopy, allergy to beta-lactam antibiotics
      and tropical fruits, are the risk factors for latex allergy.

PMID- 10086203
TI  - Nasal challenge with histamine decreases nonspecific bronchial reactivity in
      workers exposed to respiratory irritants.
AB  - BACKGROUND: A link ("naso-bronchial reflex") between nasal and bronchial
      reactivity seems to exist. The effect of nonspecific nasal challenge (standing
      for the exposure to irritative stimuli at the workplace) on lung function indices
      and nonspecific bronchial reactivity is not known. METHODS: In 80 healthy workers
      (age: 36.0 +/- 8.6 years) continuously exposed to acceptable levels of different
      respiratory irritants (for more than 2 years) nasal challenge was performed by
      spraying doubling concentrations of histamine (0.0625-16.0 mg/mL, doses of
      histamine: 7.8 micrograms-2.08 mg) into each nostril. Before and immediately
      after nasal challenge spirometry and the bronchoprovocation test with histamine
      (0.5-128 mg/mL) was performed. RESULTS: Although nasal challenge with histamine
      had not reduced airway caliber (before nasal challenge vs. following nasal
      challenge: FEV1 3.8 +/- 0.8 vs. 3.7 +/- 0.8 L, and MEF50 4.3 +/- 1.4 vs. 4.3 +/-
      1.4 L/s, mean +/- SD, respectively), it had significantly reduced nonspecific
      bronchial reactivity in 30.2% of the irritant-exposed subjects. CONCLUSIONS:
      Nasal challenge with histamine decreases nonspecific bronchial reactivity in
      workers occupationally exposed to respiratory irritants. Thus, a methodological
      implication would be that these two tests should not be performed consecutively
      in less than 2 hr in the same subjects.

PMID- 10086204
TI  - Non-specific nasal and bronchial reactivity are not correlated in non-asthmatic
      subjects occupationally exposed to irritants and in healthy subjects.
AB  - BACKGROUND: Non-specific nasal and bronchial reactivity are frequently correlated
      in disease (rhinitis and asthma). It is not known whether such a correlation
      exists in subjects exposed to irritants and in healthy subjects. In order to test
      the hypothesis that a correlation between non-specific nasal and bronchial
      reactivity exists in non-asthmatic subjects, two groups of subjects were studied:
      110 workers occupationally exposed to respiratory irritants, and 86 non-exposed
      healthy controls. METHODS: Allergy, non-specific nasal, and non-specific
      bronchial reactivity were tested, and smoking habits were categorized in each
      subject. RESULTS: Respiratory irritants cause a substantial increase in nasal and
      bronchial reactivity when compared with the group of healthy, non-exposed
      subjects (33.6% nasal hyperreactors and 20.0% bronchial hyperreactors vs. 4.7%
      nasal hyperreactors and 2.3% bronchial hyperreactors, respectively). But,
      occupational exposure to respiratory irritants does not induce a correlation
      between non-specific nasal and bronchial reactivity frequently found in asthmatic
      and rhinitic subjects. CONCLUSIONS: We found no correlation between non-specific
      nasal and bronchial reactivity either in subjects occupationally exposed to
      respiratory irritants or in the group of healthy subjects. This lack of
      correlation in both studied groups seems to be a feature of non-diseased airways.
      Smoking as an additional factor does not increase nasal and bronchial reactivity
      either in workers exposed to irritants or in healthy subjects. Smoking also does
      not strengthen the correlation between upper and lower airways' reactivity in
      both groups.

PMID- 10086205
TI  - Toward a positive contribution to understanding cost-effectiveness issues in the
      surveillance and prevention of occupational disease.

PMID- 10086206
TI  - What is the most cost-effective way to identify silica problem worksites?

PMID- 10086207
TI  - Cotton dust and endotoxin exposure and long-term decline in lung function:
      results of a longitudinal study.
AB  - BACKGROUND: To evaluate the relationship between long-term exposure to cotton
      dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11
      year follow-up study of cotton textile workers in Shanghai, China. METHODS:
      Workers at a nearby silk-thread manufacturing mill were used as a referent
      population. Ninety percent of the original cohort of 445 cotton and 467 silk
      textile workers--both active and retired--were identified for testing in the 11th
      year. Questionnaires and spirometric testing were performed, as well as cotton
      dust and endotoxin sampling at three points over the 11-year follow-up period: at
      baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick
      leave, 84% of the original cohort had complete health and environmental data.
      RESULTS: The data were reanalyzed using generalized estimating equations feedback
      model which allow for subject transfer over time between work areas, various
      exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss
      of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the
      second 6 years of follow-up (-18 mls/yr). During the same periods, the average
      decline among silk workers was slightly higher in the first period, but was more
      consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be
      explained by worker selection or dropout. When cumulative exposure to dust and
      endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss,
      cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1
      after adjustments for confounders. There was evidence of feedback between dust
      exposure levels and FEV1, indicating the existence of a healthy-worker survivor
      effect. After accounting for a healthy-worker survivor effect, we found a
      significant relationship between dust exposure and FEV1 decline. CONCLUSIONS: Our
      results suggest that cotton dust is more strongly associated with chronic airflow
      limitation than associated endotoxins. Further work is needed to clarify
      potential reversibility after cessation of exposure, and the relative
      contributions of dust, endotoxin, and tobacco to chronic respiratory impairment
      in cotton and other vegetable-exposed workers.

PMID- 10086208
TI  - Organic dust toxic syndrome in swine confinement farming.
AB  - BACKGROUND: Pig farmers are exposed to organic dust with pro-inflammatory
      capacities. This makes it likely that they suffer from organic dust toxic
      syndrome (ODTS). No studies that included unexposed control populations are
      available so far. METHODS: The prevalence of ODTS was established by the use of
      questionnaires in a group of 239 pig farmers and 311 rural controls working in
      nonagricultural occupations. RESULTS: Pig farmers suffered more often from ODTS
      than controls (6.4% vs. 2.6%, P < 0.05). Organic dust toxic syndrome was
      associated with symptoms of atopy (prevalence odds ratio (POR) 3.1, 95%
      confidence interval (CI) 1.2-8.0) and with the use of wood-shavings as bedding
      (POR 4.3, 95% CI 1.2-15.6). An inverse association with the number of years
      worked as pig farmer was found (up to 5 years vs. more than 5 years; POR 5.0, 95%
      CI 0.8-32.9). CONCLUSIONS: The prevalence of ODTS was elevated among pig farmers
      when compared to nonfarming, rural controls.

PMID- 10086209
TI  - Carpal tunnel syndrome and workers' compensation among an occupational clinic
      population in New York State.
AB  - BACKGROUND: This study evaluated the experience in the New York State workers'
      compensation (WC) system of 135 patients with work-related carpal tunnel syndrome
      diagnosed at an academic occupational medicine clinic between 1991-1994. METHODS:
      Worker's Compensation Board (WCB) records were reviewed to ascertain: (1) the
      proportion of WC claims that were not initially accepted (i.e., that were
      challenged) by the WC insurer, (2) the proportion of challenged claims ultimately
      decided in the claimant's favor, (3) the length of the period between case filing
      and claim adjudication, and (4) risk factors for claim challenge. RESULTS:
      Seventy-nine percent of the claims were not initially accepted by the WC insurer
      (challenged/no response). Of the 81 challenged/no response cases adjudicated
      (ruled on) at the time of the study, 96.3% were accepted as work-related. Mean
      time from claim initiation to adjudication was 429 days (range 58-1,617). Mean
      time from physician request for any treatment and WCB authorization was 226 days
      (range 0-1,296). Mean time from physician request for surgery authorization and
      WCB authorization was 318 days (range 7-595). Claims filed by non-whites, low
      wage workers, and union members were significantly more likely than others to be
      challenged. CONCLUSIONS: Patients with work-related carpal tunnel syndrome face
      frequent claim challenge by WC insurers in NY State, with attendant prolonged
      delays in adjudication and treatment authorization. Likelihood of claim rejection
      was strongly related to ethnicity and socio-economic status.

PMID- 10086210
TI  - Characteristics of the healthy survivor effect among male and female Hanford
      workers.
AB  - BACKGROUND: The healthy survivor effect is a selection process whereby healthy
      workers are selectively retained in the work force while unhealthy workers are
      removed. Understanding this phenomenon is integral to the accurate assessment of
      exposure effects in occupational cohorts. To date, scarce information has been
      published on the descriptive characteristics of the healthy survivor effect.
      METHODS: Follow-up mortality data on 44,154 employees from the Hanford nuclear
      facility for the period of 1944-1986 were used to estimate the healthy survivor
      effect according to frequently measured sociodemographic characteristics.
      RESULTS: While Hanford employees did not exhibit a stepwise decline in
      standardized mortality ratios according to duration of employment, workers in the
      longest employment duration category demonstrated a substantial survival
      advantage compared to the rest of the cohort. This effect was present in both
      males and females, and in all but the following subgroups: males hired at or
      after age 40, females hired before age 40, and females classified as both
      professional and nonprofessional. CONCLUSION: The findings of the present study
      suggest that investigators should consider the potential confounding role of the
      healthy survivor effect when relying on SMRs, or other methods, to assess the
      adverse health effects of exposure in occupational cohorts. Further studies
      should be conducted, however, to assess variation in the healthy survivor effect
      according to sociodemographic characteristics.

PMID- 10086211
TI  - Maternal occupational exposure to electromagnetic fields before, during, and
      after pregnancy in relation to risks of childhood cancers: findings from the
      Oxford Survey of Childhood Cancers, 1953-1981 deaths.
AB  - BACKGROUND: The concern that maternal exposure to electromagnetic fields (EMF)
      might be related to childhood cancer risks, particularly leukemia risks. METHODS:
      Maternal occupational data already collected as part of the Oxford Survey of
      Childhood Cancers have been reviewed. Information on occupations held before,
      during, and after the pregnancy was sought for 15,041 children dying of cancer in
      Great Britain in the period 1953-1981, and for an equal number of matched
      controls. Each period of working was classified under one of five headings: (1)
      sewing machinist; (2) textile industry workers (other than sewing machinists)
      with likely exposures to EMF; (3) other machinists and other jobs with likely
      "higher" EMF exposure; (4) other jobs with likely exposure to some EMF, and (5)
      jobs with little potential for EMF exposure. RESULTS: Relative to risks in the
      children of mothers who held occupations with little potential for EMF exposure
      during pregnancy (a category that included housewives), risks of all childhood
      cancers were close to unity both for the children of sewing machinists (22 case
      and 31 control mothers, RR 0.72, 95% CI 0.42 to 1.25) and for the children of
      other machinists with likely "higher" EMF exposures (44 case and 47 control
      mothers, RR 0.93, 95% CI 0.61 to 1.41). Corresponding risks for all childhood
      leukemias and for all childhood brain cancers were similarly unexceptional.
      Simultaneous adjustment for social class, maternal age at birth of child, and
      sibship position had little effect. CONCLUSIONS: The study findings did not
      indicate that maternal occupational exposure to EMF during pregnancy is a risk
      factor for childhood leukemias, childhood brain cancers, or the generality of all
      childhood cancers.

PMID- 10086212
TI  - Effects of a participatory ergonomics team among hospital orderlies.
AB  - BACKGROUND: High rates of work-related injuries are seen among health care
      workers involved in lifting and transferring patients. We studied the effects of
      a participatory worker-management ergonomics team among hospital orderlies.
      METHODS: This prospective intervention trial examined work injuries and other
      outcomes before and after the intervention, with other hospital employees used as
      a concurrent control. All orderlies in a 1,200-bed urban hospital were studied
      using passively collected data (mean employment during study period 100-110
      orderlies); 67 orderlies (preintervention) and 88 orderlies (postintervention)
      also completed a questionnaire. The intervention was the formation of a
      participatory ergonomics team with three orderlies, one supervisor, and technical
      advisors. This team designed and implemented changes in training and work
      practices. RESULTS: The 2-year postintervention period was marked by decreased
      risks of work injury (RR = 0.50, 95% CI 0.35-0.72), lost time injury (RR = 0.26,
      95% CI 0.14-0.48), and injury with three or more days of time loss (RR = 0.19,
      95% CI 0.07-0.53). Total lost days declined from 136.2 to 23.0 annually per 100
      full-time worker equivalents (FTE). Annual workers' compensation costs declined
      from $237/FTE to $139/FTE. The proportion of workers with musculoskeletal
      symptoms declined and there were statistically significant improvements in job
      satisfaction, perceived psychosocial stressors, and social support among the
      orderlies. CONCLUSION: Substantial improvements in health and safety were seen
      following implementation of a participatory ergonomics program.

PMID- 10086213
TI  - Asthma and chemical bronchitis in vanadium plant workers.
AB  - BACKGROUND: Whether vanadium induces bronchial hyperresponsiveness and asthma in
      previously normal subjects is unresolved: the two reported series addressing this
      question both have shortcomings. OBJECTIVE: To determine the cause of cough and
      breathlessness in vanadium plant workers after variable periods of exposure.
      DESIGN: Case series of employees presenting with persistent symptoms over a 24
      month study period. PATIENTS AND METHODS: Forty of an estimated 1,440 patients
      were investigated by 1) blood count and serum IgE, 2) intracutaneous allergen
      skin tests, 3) spirometry, and 4) bronchoprovocation by histamine inhalation or
      exercise challenge. Exposure was assessed by measurement of 1) ambient V2O5, NH3
      and SO2 over 7 days during the 24-month study period, 2) urine vanadium
      concentration at time of first presentation. RESULTS: Twelve of 40 subjects had
      bronchial hyperreactivity (BHR), and these were compared to 12 age-matched
      companion subjects whose BHR was normal. In 10, BHR was diagnosed by histamine
      inhalation (PC20 0.25-1.82 mg/ml, nl > 8.0 mg/ml), and in six of these the
      abnormality was severe (PC20 < 0.5 mg/ml). A further two had BHR by exercise
      challenge (FEV1, 600 ml/30% and 770 ml/18% pre/post exercise). After removal from
      exposure, 9 of the 12 subjects returned for follow-up 5 to 23 months later. BHR
      was worse in one, still present although less severe in five, and was no longer
      found in one subject. Baseline spirometry measurements were normal in seven
      subjects and only mildly impaired in the remaining five of the 12 subjects with
      BHR. CONCLUSION: This study provides strong supporting evidence that inhaled V2O5
      induces BHR and asthma in subjects previously free of lung disease; the
      abnormality may persist for up to 23 months following exposure; routine
      spirometry will not detect affected subjects.

PMID- 10086214
TI  - Connective tissue disease and silicosis.
AB  - BACKGROUND: To determine the prevalence of connective tissue disease in a cohort
      of individuals with silicosis, we reviewed the medical records and questionnaires
      from individuals reported from 1987 to 1995 to a state surveillance system for
      silicosis. Reporting of individuals with silicosis is required by state law.
      Cases were reported by hospitals, physicians, the state workers' compensation
      bureau, or from death certificates. Only individuals who met the criteria for
      silicosis developed by the National Institute for Occupational Safety and Health
      (NIOSH) were included in the analysis. RESULTS: A questionnaire was completed for
      all 583 cases. Medical records were available for 463. There were 24 people with
      rheumatoid arthritis, one with scleroderma, and one with systemic lupus
      erythematosus. All were men. The prevalence of rheumatoid arthritis was 5.2%
      (relative risk (RR) 2.73, 95% confidence limit (CL) 1.75-4.06). The prevalence of
      scleroderma was 0.2% (RR 15.65, 95% CL 0.21-87.03) and the prevalence of systemic
      lupus erythematosus was 0.2% (RR 11.37, 95% CL 0.15-63.23). This is an
      approximately 2.5-15-fold increased risk for these connective tissue diseases
      compared to estimated prevalences in the general population. Individuals with
      silicosis and connective tissue disease did not differ from individuals with
      silicosis but without connective tissue disease by race, age, type of industry
      where exposed to silica, history of tuberculosis, whether or not they had applied
      for workers' compensation, and whether or not they had progressive massive
      fibrosis on chest x-ray. CONCLUSION: Although the association between scleroderma
      and silicosis has been more widely reported in the literature, the prevalence of
      rheumatoid arthritis was greater than the prevalence of scleroderma or systemic
      lupus erythematosus among a cohort of individuals with silicosis.

PMID- 10086215
TI  - Environmental concerns regarding the use of the ivermectin sustained-release
      bolus in cattle.

PMID- 10086216
TI  - An ethicist's commentary on the client who owes $800 and sends in an animal with
      porcupine quills.

PMID- 10086217
TI  - Synchronization of estrus in beef cattle with norgestomet and estradiol valerate.
AB  - Fifty-six cows received a norgestomet implant and an injection of norgestomet and
      estradiol valerate; half (n = 28) received 500 IU equine chorionic gonadotrophin
      (eCG) at implant removal, 9 d later. A third group (n = 25) received 2 doses of
      cloprostenol (500 micrograms) 11 d apart. Estrous rate was higher (P < 0.05) for
      cows given norgestomet and estradiol plus 500 IU eCG (75.0%) than for those
      receiving cloprostenol (44.0%); for those receiving norgestomet and estradiol
      alone, it was intermediate (67.8%). Pregnancy rates to artificial insemination
      (after estrus or timed) were higher (P < 0.05) for cows given norgestomet and
      estradiol than for those given cloprostenol (23 of 28, 82.1% vs 13 of 25, 52.0%),
      and intermediate (67.8%) for those given norgestomet and estradiol plus eCG. In a
      second experiment, for heifers treated with norgestomet and estradiol plus eCG (n
      = 15) or with 2 doses of cloprostenol (n = 16), estrous rates were 66.7% vs 56.2%
      (P > 0.5), ovulation rates were 100.0% vs 81.2% (P = 0.08), intervals from
      implant removal or cloprostenol treatment to estrus were 48.0 +/- 4.4 hours vs
      61.3 +/- 7.0 hours (P = 0.12) and to ovulation were 70.4 +/- 4.4 hours vs 93.2 +/
      7.5 hours (P < 0.01), respectively; pregnancy rates were 41.7 and 35.7%,
      respectively (P > 0.5). Norgestomet and estradiol were as good as (heifers) or
      superior to (cows) a 2-dose cloprostenol regimen. In cows given norgestomet and
      estradiol, injecting eCG at implant removal did not significantly improve estrous
      or pregnancy rates.

PMID- 10086218
TI  - A comparison of florfenicol and tilmicosin for the treatment of undifferentiated
      fever in feedlot calves in western Canada.
AB  - A field trial was performed under commercial feedlot conditions in western Canada
      to compare the efficacy of florfenicol and tilmicosin for the treatment of
      undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon
      arrival at the feedlot. One thousand and eighty recently weaned, auction market
      derived, crossbred beef calves suffering from UF were allocated to one of 2
      experimental groups as follows: florfenicol, which was intramuscular (i.m.)
      florfenicol administered at the rate of 20 mg/kg body weight (BW) at the time of
      allocation (Day 0) and again 48 h later, or tilmicosin, which was subcutaneous
      (s.c.) tilmicosin administered once at the rate of 10 mg/kg BW on day 0. Five
      hundred and forty-four animals were allocated to the florfenicol group and 536
      animals were allocated to the tilmicosin group. The chronicity, wastage, overall
      mortality, and bovine respiratory disease (BRD) mortality rates were
      significantly (P < 0.05) lower in the florfenicol group than in the tilmicosin
      group. There were no significant (P > or = 0.05) differences in first UF relapse,
      second UF relapse, hemophilosis mortality, or miscellaneous mortality rates
      between the florfenicol and tilmicosin groups. Average daily gain (ADG) from
      arrival at the feedlot to the time of implanting and ADG from allocation to the
      time of implanting were significantly (P < 0.05) lower in the florfenicol group
      as compared with the tilmicosin group. There were no significant (P > or = 0.05)
      differences in arrival weight, allocation weight, implanting weight, or ADG from
      arrival to allocation between the experimental groups. In the economic analysis,
      there was an advantage of $18.83 CDN per animal in the florfenicol group. The
      results of this study indicate that florfenicol is superior to tilmicosin for the
      treatment of UF because of lower chronicity, wastage, overall mortality, and BRD
      mortality rates. However, interpretation of these observations must take into
      consideration the fact that these calves received meta-phylactic tilmicosin upon
      arrival at the feedlot, which is a standard, cost-effective, management procedure
      utilized by feedlots in western Canada.

PMID- 10086219
TI  - Ballistic shock wave lithotripsy in an 18-year-old thoroughbred gelding.
AB  - Prolonged postoperative recuperation time and restricted exercise were
      circumvented by using ballistic shock wave lithotripsy to break up an 8-cm
      diameter vesical calculus and by flushing out the sand-like residue under
      epidural anesthesia with the horse standing. Recovery was uneventful.

PMID- 10086220
TI  - Three cases of canine leptospirosis in Quebec.
AB  - Three dogs from different locations with acute renal failure were hospitalized in
      autumn 1996 and 1997. Leptospira interrogans serovar pomona was detected by the
      microscopic agglutination test. All dogs recovered after antibiotic treatment.
      The importance of the development of vaccines adapted to emerging serovars in
      dogs should be addressed.

PMID- 10086221
TI  - Selenium toxicosis in a flock of Katahdin hair sheep.
AB  - Selenium supplementation by injection is a common practice. Acute toxicosis from
      dosaging errors may occur. In this report, 23 of 56 ewes and all 24 lambs
      injected with selenium died. Tissue, whole blood, and serum concentrations aided
      in the diagnosis. Caution should be taken when supplementing selenium by
      injection.

PMID- 10086222
TI  - Fracture-luxation of the central tarsal bone in a dog.

PMID- 10086223
TI  - Chronic intermittent vomiting in a cat: a case of chronic lymphocytic-plasmacytic
      gastritis.
AB  - A 3-year-old cat presented for chronic intermittent vomiting was diagnosed with
      chronic lymphocytic-plasmacytic gastritis via histological examination of an
      endoscopic gastric biopsy. The condition was effectively managed with prednisone.
      The author cautions against missing a diagnosis of alimentary lymphosarcoma
      without a full-thickness gastric biopsy.

PMID- 10086224
TI  - Understanding airway disease in infants.
AB  - Large airway diseases manifest in ways distinct from those of small airway
      diseases. Noisy breathing that begins early in life suggests a congenital lesion
      of the large airways. The findings of elevated respiratory rate, in conjunction
      with subcostal retractions, hyperinflation to percussion, and musical wheezes,
      are diagnostic of small airway obstruction. Differentiating large from small
      airway disease is crucial, because each disease has a distinct diagnosis, and
      treatment of the 2 disease types can be quite different. When these principles
      are applied to a patient with wheezing or other signs of airway compromise, it
      becomes fairly easy to differentiate large from small airway disease. The
      treatment of patients with large airway disease can be substantially different
      from that of patients with small airway disease. Being able to differentiate the
      two is critically important. With the use of the history, physical examination,
      and radiographic evaluations described earlier, nearly every patient can be given
      an accurate diagnosis and treated appropriately.

PMID- 10086225
TI  - Stressors and concerns in teen asthma.
AB  - Adolescents are uniquely susceptible to poor outcome with asthma because of their
      desire for autonomy, denial of disease, preference for immediate gain rather than
      prophylaxis, restricted ability to control their psychosocial and physical
      environment, and difficult transition to health care. Tobacco smoking as well as
      related drug abuse and passive exposure to tobacco is a major obstacle to
      managing adolescent asthma, together with atopy and psychosocial problems. Recent
      investigations indicate that adolescents are uniquely susceptible to tobacco
      industry promotions and logos because of these developmental characteristics. By
      understanding adolescent development, behavior and peer group impact, with its
      spectrum from early to late adolescence, clinicians can target their educational
      interventions more successfully in asthma. Health care provision for the
      adolescent with asthma requires a multidisciplinary team spearheaded by a primary
      care provider with the expert guidance of an allergist, outreach nurse, mental
      health worker, and social service representative. This care must be negotiated
      with an appropriate educational plan on the basis of NHLBI guidelines to be
      successful. Medications should be prescribed no more than twice a day, whenever
      possible, in conjunction with an action plan on the basis of peak flow readings
      to warn the adolescent when to use more medication and when to call the
      clinician. The plan should empower adolescents by recognizing their need for
      autonomy with self-management, enabling them to have a safe and comfortable
      lifestyle, and being physically and mentally at ease with their peers, family,
      school, and work environments.

PMID- 10086226
TI  - Ontogenetic adaptation and learning: a developmental constraint in learning for a
      thermal reinforcer.
AB  - Hoffman, Flory, and Alberts (1999) demonstrated that 1-, 5-, and 11-day-old rats
      in a cool environment (25 degrees C) acquired an operant head-turning response
      when rewarded with a 20-s warming of the platform on which they lay. In the
      current experiment 5- and 11-day-old rats in a hot environment (40 degrees C)
      acquired the head-turning response when rewarded with a 20-s cooling of the
      platform on which they lay, but 1-day-olds did not. The concept of ontogenetic
      adaptation helps us interpret these results: Neonatal thermotaxis constrains the
      1-day-olds from learning a novel operant response for a cool reinforcer in a hot
      environment. Because the thermotaxis wanes from birth, it is not as strong in 5-
      and 11-day-old pups that are thus able to learn the operant for a cool
      reinforcer.

PMID- 10086227
TI  - Neonatal thermotaxis improves reversal of a thermally reinforced operant
      response.
AB  - One-, 5-, and 11-day-old rats in a cool environment (25 degrees C) acquired an
      operant response when rewarded with a 20-s-long warming of the platform (from 25
      to 36 degrees C) on which they lay. In Experiment 1, the head-turning response
      was learned by pups at all ages. When the contingency was reversed so that pups
      were reinforced for turning to the side opposite that correct during training,
      the original response extinguished for 1-day-olds, but not for 5- or 11-day-olds.
      In Experiment 2, the rewarded side was randomly selected for each trial. One-day
      olds perseverated in turning to the side correct on that trial while the
      reinforcer remained on, but 5- and 11-day-old rat pups did not. We conclude that
      1-day-old pups were more responsive to the change in experimental contingency in
      Experiment 1 due to this thermotaxic behavior.

PMID- 10086228
TI  - Behavioral specificity of effects of 2-mercaptoacetate on independent ingestion
      in developing rats.
AB  - Blockade of fatty acid oxidation in rat pups using 2-Mercaptoacetate (MA)
      produces increases in independent ingestion by 12 days of age. In the present
      experiments, the behavioral specificity of the effects of MA on ingestion were
      examined. In the first experiment, administration of MA to pups aged 9 and 12
      days of age failed to increase intake of an oral infusion of a milk diet. In the
      second experiment, administration of MA did enhance intake of a milk diet in a
      short-term test of consuming from the floor of a test container and the level of
      gastric fill appeared to determine intake during the test. Finally,
      administration of MA did not affect intake of water in 9- or 12-day-old pups.
      These results suggest that MA produces increases in intake through specific
      effects on selective ingestive responses and not through nonspecific behavioral
      arousal.

PMID- 10086229
TI  - The effects of 8-OH-DPAT and (+/-)-pindolol on isolation-induced ultrasonic
      vocalizations in 3-, 10-, and 14-day-old rats.
AB  - It has been established that administration of 5-HT1A agonists attenuates the
      rate of isolation-induced ultrasonic vocalizations (USV) in 10-day-old rat pups.
      In this study we extended these findings by examining the effects of
      administration of the serotonergic 1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT), and mixed 5-HT1A antagonist/beta adrenergic
      antagonist, (+/-)-pindolol, in 3-, 10-, and 14-day-old rat pups in order to
      assess the effect of these drugs from a developmental perspective. At all three
      ages, 8-OH-DPAT significantly reduced the rate of isolation-induced USV. While
      only the highest dose (1.0 mg/kg) of 8-OH-DPAT administered to the 10- and 14-day
      olds significantly reduced the rate of vocalization, both the 0.1- and 1.0-mg/kg
      doses significantly attenuated the vocalization rate in the 3-day-olds. Pindolol
      administration did not alter the rate of USV at any age nor did it block the
      quieting effect that generally occurs when an anesthetized littermate is placed
      with the isolated pup. We conclude that 8-OH-DPAT is effective as early as 3 days
      of age in the quieting of isolation-induced USV and that the regional age
      dependent development of 5-HT1A receptors and projections are important factors
      in the observed differential sensitivity to 8-OH-DPAT administration during
      development.

PMID- 10086230
TI  - Delay of gratification in chimpanzees (Pan troglodytes).
AB  - Delay of gratification in 3 chimpanzees (Pan troglodytes) was examined by using a
      paradigm based on research with children. The chimpanzees either pressed a door
      bell button during a trial and received one reward (the immediate reward) or did
      not press the doorbell and received another reward (the delayed reward). Two
      chimpanzees were language-trained, and a 3rd was non-language-trained. Foods (one
      more-preferred and one less-preferred), photographs of those foods, or lexigrams
      representing those foods were presented to the chimpanzees. All 3 chimpanzees
      delayed gratification when foods were physically present. One language-trained
      chimpanzee also delayed gratification with lexigrams present, and the 2nd
      language-trained chimpanzee delayed gratification in all three conditions.
      Language competence and early rearing are proposed as explanations for the
      different performances of these chimpanzees.

PMID- 10086231
TI  - Play is indispensable for an adequate development of coping with social
      challenges in the rat.
AB  - In this study, young rats were deprived of early social interactions during weeks
      4 and 5 of life. Different behavioral tests were conducted in adulthood to study
      the behavioral responses of rats lacking early social experiences. Juvenile
      deprivation resulted in decreased social activity and an altered sexual pattern,
      but did not affect locomotor activity or the performance in the elevated plus
      maze. Furthermore, behavioral and neuroendocrine responses of juvenile isolated
      rats were dramatically altered when they were confronted with territorial
      aggression. Juvenile deprived rats did not readily display a submissive posture
      in response to the resident and showed no immobility behavior after being
      returned to the resident's territory, while their plasma corticosterone and
      adrenaline concentrations were significantly increased compared to nonisolated
      controls. In contrast, behavioral responses in the shock prod test were not
      affected by previous isolation. The results suggest that early social experiences
      are vital for interactions with conspecifics later in life, i.e., aggression,
      sexual, and social interactions.

PMID- 10086232
TI  - Preweanling sensorial and motor development in laboratory mice: quantitative
      trait loci mapping.
AB  - Chromosomal mapping of genes linked with 19 measures of sensorial, motor, and
      body weight development were investigated. Chromosomal mapping is the first step
      towards gene identification. When a genomic region is shown to be linked to a
      trait, it is possible to select a reduced number of candidate genes that have
      been previously mapped on this region. The involvement of every gene can be
      individually tested either by molecular (transgenesis, homologous recombination)
      or traditional methods (congenicity). Mapping was performed using 389 males and
      females from two inbred strains of laboratory mice C57BL/6By and NZB/BlNJ, their
      reciprocal F1s and F2s. Thirty-six Quantitative Trait Loci (QTL) were mapped, 12
      reached the 3.13 lod score, being thus considered as confirmed. These QTL were
      tentatively labeled: Cliff Drop Aversion (Cliff Qtl), Geotaxia (Geot Qtl),
      Vertical Clinging (VertCling Qtl), Bar Holding with the 4 paws (BH4P Qtl), Age at
      Eyelid Opening (Aeyo Qtl), Visual Placing (Vispl Qtl), Startle Response (Start
      Qtl1, Start Qtl2), Body Weight at Day 10 in Males pooled with Females (Bwefmd10
      Qtl), and Body Weight at Day 30 in males (Bwemd30 Qtl). For the majority of the
      developmental measures, the QTL that were mapped contributed little to the
      phenotypic variance, even when mitochondrial DNA contribution was included:
      Righting Response (12.7%), Cliff Drop Aversion (10%), Crossed Extensor Response
      (18.1%), Geotaxia (16.2%), Bar Holding Response for 10 s (12.1%), Bar Holding
      Response with 4 paws (8.1%), Vertical Clinging (9.3%), Vertical Climbing (5%),
      Startle Response (21.2%), Eyelid Opening (14.6%), Visual Placing (22%), Body
      Weight at Day 10 (27%), Body Weight at Day 15 in Females (52.5%), Body Weight at
      Day 15 in Males (17%), Body Weight at Day 30 in Females (42%), and Body Weight at
      Day 30 in Males (48%). A factorial analysis of the correlations between the
      measures of development did not provide evidence of a general factor. A general
      genetic factor of development was also rejected because few common genetic
      correlates were discovered for the 19 measures of development (Body Weight at
      Days 15 and 30 in Females on Chromosome 2, Eyelid Opening and Body Weight at Day
      10 on Chromosome 5 and mitochondrial genome for five measures). Co-identification
      of genes, the function of which were previously known thanks to newly discovered
      QTL, should help to explain the function of QTL. Present data help to highlight
      candidate regions including several genes that could be candidates for the QTL
      function. Large confidence intervals were obtained as usual from the F2
      intercrossed population. More stringent methods are suggested for more efficient
      co-identification.

PMID- 10086233
TI  - Occurrence of intercellular spaces (windows) in metastatic adenocarcinoma in
      serous fluids: a cytomorphologic, histochemical, and ultrastructural study.
AB  - The application of cytomorphologic criteria to the examination of serous
      effusions allows the reliable diagnosis of malignancy in the majority of cases.
      One feature observed in tissue fragments previously thought to be indicative of
      mesothelial origin is the presence of intercellular windows, presumably due to
      long surface microvilli. In this study, however, we examined cytologic
      preparations of 143 effusion and body-cavity washing specimens and noted distinct
      intercellular window formation within tissue fragments of adenocarcinoma in 13%
      of the cases studied. Stains for mucicarmine, Alcian blue with hyaluronidase
      pretreatment, and periodic acid-Schiff following diastase digestion on
      corresponding cell block material demonstrated that intercellular mucin
      contributes to such window formation in greater than half of these cases. Thus
      the presence of intercellular windows within tissue fragments does not, in
      isolation, preclude the diagnosis of malignancy in serous effusions.

PMID- 10086234
TI  - Fine-needle aspiration cytology and immunocytochemistry of soft-tissue
      extramedullary plasma-cell neoplasms.
AB  - This study presents 19 patients with extramedullary plasma-cell tumors diagnosed
      by fine-needle aspiration (FNA) cytology together with immunocytochemistry. Eight
      patients had primary extramedullary plasmacytoma, while 11 patients had tumors
      secondary to myeloma. The most common localization was soft tissue (9 cases),
      followed by lymph nodes (5), scalp (3), and oral and nasal mucosa (2). All FNA
      smears were cellular, and 12 cases showed dissociated monomorphic plasma cells.
      Seven cases showed a dominance of immature bare nuclei, which made then difficult
      to diagnose conclusively using cytomorphology only. Immunocytochemistry
      demonstrated monoclonal expression of light immunoglobulin chains in all cases
      which, together with demonstration of CD 38 positivity and cytomorphology,
      allowed a conclusive diagnosis of plasmacytoma.

PMID- 10086235
TI  - E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad,
      the worthless.
AB  - The distinction between reactive mesothelial cells (RMC), malignant mesothelioma
      (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible
      based on morphology alone. E-cadherin, N-cadherin, and calretinin are newly
      described immunocytochemical markers which can potentially be utilized for
      facilitating this distinction. E-cadherin and N-cadherin are calcium-dependent
      intercellular adhesion molecules expressed in epithelial cells and
      mesenchymal/mesothelial cells, respectively. The differential expression of E
      cadherins in epithelial cells and N-cadherins in mesothelial cells has been
      utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is
      a calcium-binding protein within the family of EF-hand proteins. It is abundantly
      expressed in peripheral and central nervous tissues, and has been shown to
      consistently immunoreact with mesothelial cells. We studied cell block sections
      from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the
      potential immunocytochemical use of anti-E-cadherin, anti-N-cadherin, and anti
      calretinin antibodies for differentiating between RMC, MM, and ACA in pleural
      effusions. A modified avidin-biotin peroxidase complex (ABC) method was used. E
      cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs.
      A distinct membrane staining pattern was seen in ACAs. The pattern of staining
      was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in
      MMs. Anti-N-cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs.
      Twenty-seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti
      calretinin. Based on these results, we conclude that anti-E-cadherin is a
      potentially useful marker in the distinction of ACA cells from RMC. However, it
      is not as useful for the distinction of ACA and MM. Anti-N-cadherin and anti
      calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA
      cells in pleural effusions.

PMID- 10086236
TI  - Fine-needle aspiration cytology and immunocytochemistry of soft-tissue tumors and
      osteo/chondrosarcomas of the head and neck.
AB  - The purpose of the study was to present the clinical and cytological findings of
      28 cases of malignant or borderline mesenchymal tumors of the head and neck, of
      which 22 originated from soft tissue and 6 were found in bone or cartilage. The
      basic procedures employed involved a cytologic review and subclassification of
      fine-needle aspiration (FNA) smears from the tumors, which were diagnosed as:
      pleomorphic sarcomas (5 poorly differentiated, 1 angiosarcoma, and 1 epithelioid
      sarcoma), spindle-cell sarcomas (2 leiomyosarcomas, 2 malignant mesenchymal
      tumors, and 1 malignant schwannoma), myxoid sarcomas (2 liposarcomas and 1 high
      grade tumor), round-cell tumors (1 malignant histiocytic tumor and 1 chloroma),
      osteosarcomas (3), chondrosarcomas (3), and borderline tumors (2 pleomorphic
      lipoma, 1 myxolipoma, 1 cranial fasciitis, and 1 fibromatosis). Histological
      correlation and problems in subtyping on both cytologic and histological material
      are discussed. It is concluded that FNA cytology can be used with high accuracy
      to diagnose musculoskeletal tumors in rare sites such as the head and neck.

PMID- 10086237
TI  - Intraoperative cytologic diagnosis of suprasellar and sellar cystic lesions.
AB  - The intraoperative distinction of craniopharyngiomas (CP) and cystic pituitary
      adenomas (PA) from other intracranial parasellar cystic lesions can significantly
      modify the extent of surgery and reduce postoperative morbidity. Frozen-section
      diagnosis may be limited by the scant tissue available for examination. The
      imprint cytology of six parasellar cystic lesions is examined, along with their
      radiologic and histologic findings. These include two Rathke's cleft cysts (RCC),
      three CP, and one cystic PA. RCC showed scattered clusters of cuboidal cells with
      prominent cilia. Cystic PA demonstrated clusters of monomorphic round cells with
      minimal cytoplasm. CP displayed "wet" keratin and clusters of squamous cells with
      a palisaded border. In all six cases, cytology supported the final histologic
      diagnosis. In one case, the intraoperative diagnosis was based solely on
      cytologic examination. Cytology can contribute significantly to an accurate
      intraoperative diagnosis of parasellar cystic lesions and potentially modify
      surgical management.

PMID- 10086238
TI  - Papillary formations in metastatic melanoma.
AB  - Cytomorphologic features of melanoma can be extremely variable, in that they can
      mimic other poorly differentiated neoplasms. Ten cases of metastatic melanoma
      with distinct, cohesive, papillary tissue fragments observed in fine-needle
      aspiration (FNA) specimens are reported. These papillary fragments exhibited a
      central fibrovascular core with attached tumor cells, in a background of single
      scattered malignant cells, macrophages, and focal necrosis. The aspiration sites
      included regional or distant palpable lymph nodes, pancreas, bone, and skin. Nine
      cases had a histologic diagnosis of primary cutaneous melanoma, and in one case
      the primary skin tumor was detected after the diagnosis was established by FNA of
      the metastasis. Immunohistochemical studies (S-100 protein, HMB-45 antigen, and
      factor VIII) were performed in four cases, and electron microscopy in one,
      confirming the diagnosis of melanoma. An awareness of this cytomorphologic
      variation of papillary formations in cytology preparations from metastatic
      melanoma is important and can prevent potential inaccurate interpretation.

PMID- 10086239
TI  - Metastatic melanoma of the vulva identified by peritoneal fluid cytology.
AB  - Malignant melanoma of the vulva is an uncommon disease, with a significant
      portion of cases demonstrating metastasis to inguinal lymph nodes with potential
      distal spread. Identification of such metastases often requires fine-needle
      aspiration or biopsy. The cytologic diagnosis of metastatic vulvar melanoma from
      peritoneal effusions has not been previously described. We present the case of a
      54-yr-old woman who underwent en bloc radical vulvectomy with bilateral inguinal
      lymphadenectomy for melanoma of the right labium minora. No evidence of
      metastatic disease was identified, and all surgical margins were free of tumor.
      Despite chemotherapy, the patient returned approximately 2 yr later with
      abdominal pain and distention. Computed tomography revealed marked ascites and
      three hepatic lesions. Cytologic examination of the ascites revealed recurrent,
      metastatic melanoma. Although very rare, metastatic melanoma of the vulva may
      present as a malignant effusion. In such an event, the diagnosis may be rendered
      by exfoliative cytology.

PMID- 10086240
TI  - Cytologic diagnosis of metastatic ovarian adenocarcinoma in the urinary bladder:
      a case report and review of the literature.
AB  - A 53-yr-old woman with a 13-mo history of recurrent ovarian papillary serous
      adenocarcinoma presented with persistent microscopic hematuria. The patient was
      undergoing chemotherapy for her recurrent ovarian tumor when she was referred to
      the urology service for microscopic hematuria. An intravenous pyelogram was
      normal. Cystoscopy was performed, as well as a urinary bladder washing and
      mucosal biopsies for examination. Adenocarcinoma similar to the patient's primary
      ovarian tumor was detected in both cytology and histopathology specimens. Ovarian
      carcinoma comprises 1.3-4.0% of all metastatic neoplasms to the urinary bladder
      and is an important consideration in the differential diagnosis of a cytologic
      finding of adenocarcinoma in urine specimens of female patients, where it
      accounts for an even higher percentage of cases (1 of 3 adenocarcinoma diagnoses
      in a series of 4,677 urine specimens from female patients).

PMID- 10086241
TI  - Fine-needle aspiration cytology of cystic hypersecretory ductal carcinoma in situ
      of the breast: a case report.
AB  - Cystic hypersecretory intraductal carcinoma is an unusual, cystic form of
      intraductal breast carcinoma affecting middle-aged women. Cytopathologists have
      rarely encountered this lesion, with only 2 other cases having been previously
      reported (Colandrea et al., Arch Pathol Lab Med 1988:112:560-563; Kim et al.,
      Acta Cytol 1997;41:892-896). In our cases, the cytologic findings of both air
      dried, Diff-Quick-stained and ethanol-fixed, Papanicolaou-stained smears are
      presented. The cytologic hallmarks of this entity include the presence of a few
      scattered epithelial cells with bland nuclear morphology in a background of
      extensive, amorphous, pink-staining material. Cytomorphologically, the
      differential diagnosis includes other entities containing pink-staining material
      such as colloid carcinoma, mucocele-like lesion of the breast, and benign
      fibrocystic change.

PMID- 10086242
TI  - Atypical chondroma of the cricoid cartilage: fine-needle aspiration cytologic and
      histopathologic findings.
AB  - Chondroma of the laryngeal skeleton is a rare, benign neoplasm manifested either
      as a neck mass or, if situated within the airway, as slowly progressive
      obstruction, hoarseness, or dyspnea. The most common site is the posterior plate
      of the cricoid cartilage. An atypical perichondrial chondroma arising from the
      anterior plate of the cricoid cartilage membrane as a neck mass in a young female
      is presented. The diagnosis was made on a fine-needle aspiration of the mass and
      subsequently confirmed by histologic examination of the excised mass. Although
      rare, cartilaginous tumors of the laryngeal skeleton can manifest as a neck mass,
      and the diagnosis can be made by fine-needle aspiration biopsy in combination
      with radiographic and clinical examinations. Therefore, the existence and
      inclusion of these tumors in the differential diagnosis of neck masses by
      aspiration biopsy should be considered by clinicians and pathologists, and
      especially cytopathologists, when cartilaginous components are encountered.

PMID- 10086243
TI  - Fine-needle aspiration cytology of polymorphous low-grade adenocarcinoma of the
      tongue.
AB  - The cytologic features derived from a fine-needle aspiration of polymorphous low
      grade adenocarcinoma (PLGA) of the base of the tongue are described. The tumor
      cells were composed of cuboidal epithelial cells and short, spindle-shaped
      myoepithelial-like cells, and they formed large cell clusters. In the central
      portion of the clusters, myxoid materials were present, and palisading tumor
      cells occasionally surrounded them. Histological examination revealed solid
      proliferation of the epithelial cuboidal and spindle cells. The former frequently
      formed tubular and papillary structures. The tumor was not encapsulated, and
      invasion of adjacent muscle tissue was noted. Although the cytologic
      differentiation from cellular variants of pleomorphic adenoma and myoepithelioma
      is difficult, the feature of palisading tumor cells may be useful in the
      differential diagnosis.

PMID- 10086244
TI  - Improved quality-control detection of false-negative Pap smears using the Autopap
      300 QC system.
AB  - Federally-mandated quality control (QC) in Papanicolaou (Pap) smear testing
      requires rescreening of 10% of negative smears, to include cases selected
      randomly as well as smears from patients that may have a higher risk for
      developing cervical cancer based on clinical information. FDA approval of
      NeoPath's AutoPap 300 QC system (NeoPath, Inc., Redmond, WA) allows practical QC
      rescreening of all negatives. We tested the ability of AutoPap to help increase
      identification of detection errors compared to random 10%/high-risk selection.
      From March 1-August 30, 1997, we utilized AutoPap/high-risk status to select
      cases for manual rescreen, and compared the rate of identification of primary
      screening errors to that for the preceding year using 10% random selection/high
      risk status. Of 35,027 smears accessioned, 31,240 (89.1%) were screened as
      negative and 7,965 were selected for manual rescreen. Of these, 353 were
      determined to be abnormal. Most abnormals identified by this protocol were
      classified as atypical squamous or glandular cells of undetermined significance
      (ASCUS or AGUS). However, 59 low-grade squamous intraepithelial lesions (LSIL)
      and 13 high-grade squamous intraepithelial lesions (HSIL), many with few abnormal
      cells, were also identified. These results represented an increase in pickup rate
      of false negative due to detection errors of 2.3-, 2.8- and 5.6-fold for atypical
      squamous or glandular cells of undetermined significance, LSIL, and HSIL,
      respectively, when accounting for the volume differences over the time period
      measured. Our findings strongly support the conclusions drawn from clinical
      trials of the AutoPap that false negatives due to detection error can be
      significantly reduced when using AutoPap as part of a routine quality control
      program.

PMID- 10086245
TI  - Fine-needle aspiration biopsy of malignant testicular Leydig (interstitial) cell
      tumor.

PMID- 10086246
TI  - Cytologic detection of endometrial pathology by Pap smears.

PMID- 10086247
TI  - Reporting a series of fine needle aspirations.

PMID- 10086248
TI  - Thinking versus knowing is questioned.

PMID- 10086249
TI  - Evaluating without fear.

PMID- 10086250
TI  - "Sparkle:" a case for primary care and psychiatry.

PMID- 10086251
TI  - A cost construction model to assess the cost of a family practice residency
      program.
AB  - BACKGROUND AND OBJECTIVES: This study uses a cost construction approach to
      evaluate the cost of training family practice residents in a university-based
      residency program. The approach calculates the cost of the educational program
      from a global institutional perspective, including all monetary and nonmonetary
      costs, independently of how they are financed. METHODS: Cost construction
      analysis is used to compute the instructional cost, which includes the cost of
      faculty and resident time directly related to teaching and the support of the
      teaching program. The value of the clinical care and supervision provided by the
      family practice residents is assessed as a replacement cost. Sensitivity analysis
      examines a range of assumptions concerning residents' productivity, replacement
      costs, and the cost allocation of activities that jointly produce clinical care
      and education. RESULTS: For a junior resident, the instructional cost is $94,835
      per year, and the replacement cost is $65,052 per year. The value of the teaching
      and clinical services provided by senior residents, $124,247 per year, exceeds
      the cost of the resources used to educate them, $98,364 per year. CONCLUSIONS:
      The cost construction model can be used as a tool to allocate resources,
      negotiate for funding, and estimate variations in cost due to changes in
      curriculum and in the health care environment.

PMID- 10086252
TI  - Student and faculty perceptions of problem-based learning on a family medicine
      clerkship.
AB  - BACKGROUND AND OBJECTIVES: The value of problem-based learning (PBL) in the
      preclinical years of medical school has been described widely in the literature.
      This study evaluates student and faculty perceptions of PBL during the clinical
      years of medical school, on a family medicine clerkship. METHODS: Students used a
      4-point scale to rate clerkship educational components on how well learning was
      facilitated. Faculty narratives of their perceptions of PBL were reviewed.
      RESULTS: Educational components that involved active learning by students-
      clinical activity, independent learning, and PBL tutorials--were ranked highest
      by students. Faculty perceived that PBL on the clerkship simulated "real-life"
      learning, included more behavioral and population issues, and provided
      substantial blocks of student contact time for improved student evaluation.
      CONCLUSIONS: Students and faculty in a family medicine clerkship ranked PBL
      sessions higher than any other nonclinical component of the clerkship. In
      addition to providing students with opportunities for self-directed learning, the
      PBL sessions provide faculty with more contact time with students, thereby
      enhancing the assessment of students' learning and progress.

PMID- 10086253
TI  - Right from the start: the family practice orientation study.
AB  - BACKGROUND AND OBJECTIVES: Orientation to a residency program introduces
      residents to the essential functions of their duties, clarifies expectations, and
      acclimates them to a new social group. This study identified the orientation
      goals of family practice residency directors and compared those goals to the
      perceived needs of first-year family practice residents. METHODS: We surveyed
      program directors and PGY-1 residents at 100 accredited family practice residency
      programs. Questionnaires obtained descriptive information about orientation
      programs and resident demographics and assessed directors' goals and residents'
      needs from orientations. RESULTS: The orientation goal ranked most highly by
      directors was development of group cohesion. The need ranked most highly by
      residents was introduction to call duties and inpatient problems. Ranked
      responses of each group were not well associated. CONCLUSIONS: The orientation
      goals of program directors and the reported orientation needs of residents were
      poorly associated. Most directors chose nonclinical areas as their most important
      goals for orientation. In contrast, most residents valued clinically related
      information during orientation to residency.

PMID- 10086254
TI  - Balint seminar leaders: what do they do?
AB  - BACKGROUND: Balint seminars are part of the education of family practice
      residents in an estimated 30% of programs. Balint leaders are family physicians,
      psychiatrists, psychologists, and social workers with apprenticeship-type
      training. Balint leaders or Balint groups have never been formally evaluated.
      METHODS: We used multiple qualitative methods, including field observations,
      interviews, and focus groups. Field observations involved 12 Balint groups in 3
      family practice residency programs. For comparison, we used videotaped seminars
      of 2 groups from the most recent Balint International meeting. In-person or
      telephone interviews were conducted with Balint leaders in a number of sites. We
      conducted focus groups with resident participants at each of the local sites.
      RESULTS: Although differences were seen among groups influenced by the group
      leader and the makeup of the group, there were consistencies across all of the
      groups. Contrary to the usual description of Balint leadership, these residency
      groups functioned partially as support groups, attempted to relieve or dampen
      anxiety, had a hierarchical system with the leader as the teacher/controller, and
      served an educational and a developmental purpose. CONCLUSIONS: Balint leaders
      and their groups in the program studied did not function as traditionally
      described by Balint. Further observations of more groups are needed to determine
      if this variation is unique to the programs studied or is a manifestation of the
      transfer of the Balint method from experienced practitioners to physicians in
      training. This information will be of benefit to the development of appropriate
      training for future Balint leaders and for the credentialing process now being
      developed by the American Balint Society.

PMID- 10086255
TI  - Physician practice style patterns with established patients: determinants and
      differences between family practice and general internal medicine residents.
AB  - BACKGROUND AND OBJECTIVES: This paper examines the practice style patterns of
      family practice and internal medicine residents for established patient visits.
      METHODS: New adult patients (n = 509) were prospectively and randomly assigned to
      family practice or internal medicine clinics at a university medical center and
      followed for 1 year of care by resident physicians. Initial and return visits
      were videotaped, and physician practice styles were analyzed using the Davis
      Observation Code (DOC). RESULTS: Resident physicians' practice styles with
      established patients during return visits were associated with various factors,
      depending on the DOC cluster of behaviors studied. These factors include patient
      gender, age, income, physical and mental health status, level of pain, number of
      return visits, and physician practice style displayed during the initial
      encounter. Family practice return visits had a greater emphasis on preventive
      services and counseling, compared with internal medicine return visits.
      Internists spent more visit time using technically oriented behaviors.
      CONCLUSIONS: Patient variables, as well as baseline physician behavior, have an
      important influence on physician practice styles during return patient visits.
      There are measurable differences in the established practice styles between
      family practice and internal medicine resident physicians, which may reflect
      differences in professional training programs.

PMID- 10086256
TI  - Medical students' attitudes toward abortion and other reproductive health
      services.
AB  - BACKGROUND AND OBJECTIVES: The continued availability of legal abortions in the
      United States depends on the willingness of future physicians to provide this
      procedure. This paper explores the attitudes toward abortion issues of first- and
      second-year medical students at a large regional primary care-oriented medical
      school. METHODS: We anonymously surveyed 286 first- and second-year medical
      students at the University of Washington. RESULTS: The response rate to the
      written survey was 76.6%. Women were slightly overrepresented among the
      respondents. The majority of students supported the broad provision of
      reproductive health services; 58.1% felt that first-trimester abortions should be
      available to patients under most circumstances. Of the 43.4% of students who
      anticipated a career in family practice, most expected to provide abortions in
      their future practices. Older students and women were more likely to support the
      provision of abortion services. CONCLUSIONS: Despite continuing pressure on
      abortion providers, most first- and second-year medical students at a fairly
      typical state-supported medical school intend to incorporate this procedure into
      their future practices.

PMID- 10086257
TI  - Teaching medical students cancer risk reduction nutrition counseling using a
      multimedia program.
AB  - BACKGROUND AND OBJECTIVES: There are many barriers to medical students receiving
      education about the linkage between nutrition and cancer, including the lack of
      role models and teachers and insufficient curricular time. We tested the use of a
      multimedia program as a possible solution to teaching diet-risk assessment and
      counseling skills. METHODS: Images of Cancer Prevention, The Nutrition Link is a
      CD-ROM multimedia program that was developed and evaluated by 147 medical
      students. Pre-use and post-use surveys, computer log files, and recorded response
      sessions were used to determine the learner's 1) ease in using the program, 2)
      attitudes about the treatment of the content, 3) knowledge gain, and 4) attitudes
      about the role of physicians in nutrition assessment and counseling for cancer
      risk reduction. RESULTS: Students improved their knowledge of dietary guidelines
      for cancer risk reduction and made positive changes in their attitudes toward the
      role of physicians in dietary counseling. However, most students reported that
      they would not use the program unless it was required that they do so.
      CONCLUSIONS: The multimedia program was successful; it affected students'
      knowledge and attitudes concerning nutrition as a modifiable risk factor for some
      cancers. In addition, the design and delivery of the multimedia product was
      positively reviewed by the students for ease of access, message design,
      individualized instruction, and flexibility. Despite these favorable ratings, it
      was not clear that students would use the program unless required to do so.

PMID- 10086258
TI  - Family medicine training grants as a method of faculty development: are we doing
      it right?

PMID- 10086259
TI  - [Bladder carcinogenesis].

PMID- 10086260
TI  - [Tubeless cutaneous ureterostomy through a single stoma with new extraperitoneal
      ureteral route up to stoma].
AB  - Tubeless cutaneous ureterostomy through a single stoma has been said to be
      difficult to establish in patients with normal ureters or normal ureters combined
      with thick fatty abdominal wall, because of the poor blood supply at the end of
      the ureters. The technical improvements observed were as follows: 1) The
      peritoneal fold and the upward traction of the gonadal vessels decrease the
      ureteral tension and keep the blood supply to the ureters in the extraperitoneal
      approach. 2) The gonadal vessels and its surrounding tissue, covering the
      subcutaneous fatty tissue, help the ureteral adhesion at the anastomotic site. 3)
      Full diminution of the skin defect caused by flap formation, decreases the
      horizontal tension of the side-to-side anastomized ureters. Sixteen patients with
      normal ureters underwent this procedure. In a short-term (4-37 months)
      observation, 4 of the patients, including one with thick abdominal fat, showed
      unilateral hydronephrosis and 2 patients unilateral non-function kidney. The
      remaining 10 patients had no complications. Moreover, all the patients have kept
      their ureterostomies tubeless and their serum blood urea nitrogen and creatinine
      levels were within normal limits except for one patient. It is reasonably
      concluded that the new method will result in success clinically even in patients
      with normal ureters and thick abdominal fatty tissue.

PMID- 10086261
TI  - [Clinical study of radical cystectomy and urinary reconstruction in elderly
      patients with bladder cancer].
AB  - We compared the clinical and functional results of radical cystectomy and urinary
      reconstructions performed on 19 elderly bladder cancer patients over 75 years old
      to those on 22 younger patients to determine whether age was one of the critical
      points for the application of this type of surgery. Between January 1992 and
      January 1998, bladder substitution was performed after cystectomy using either
      the Hautmann, Studer or Reddy procedure in 9 of the 19 elderly patients. Urinary
      diversion was performed after cystectomy using ileal conduit and
      ureterocutaneostomy procedures in the rest of the patients. On the other hand,
      bladder substitutions were performed in 11; urinary diversions with continent
      urinary reservoir in 6 and with ileal conduit in 4 of the 22 younger patients.
      Neither prolongation of the operation time, nor increase in the amount of
      bleeding or prolongation of the post-operative hospitalization period was
      observed in any procedure used for elderly patients in comparison with younger
      ones. In elderly patients, the average operation time of radical cystectomy with
      bladder substitution was slightly longer than that of total cystectomy with ileal
      conduit or ureterocutaneostomy. The post-operative hospitalization period in the
      case of bladder substitution was similar to that for ileal conduit and
      ureterocutaneostomy with the difference of only 5 days on average. There were no
      peri-operative deaths, and early post-operative complications were observed in 3
      of 9 cases of the bladder substitution, in 4 of 10 cases of ileal conduit or
      ureterocutaneostomy. Five cases of bladder substitution maintained their
      comfortable voiding urine comfortably, while 4 had dysuria and/or urinary
      incontinence. Over all, late complications occurred in 10 of the elderly
      patients. The rate and types of complications in the elderly patients were not
      different from those in the younger patients. The cause-specific survival rate
      and overall survival rates of the elderly patients were similar to those of the
      younger patients. In conclusion, indication of cystectomy and selection of
      urinary reconstruction procedure are not dependent on patient's age, Orthotopic
      urinary reservoir was found to be useful for even an elderly patient.

PMID- 10086262
TI  - [RT-PCR assay for detecting PSA mRNA in peripheral blood of prostate cancer
      patients].
AB  - A sensitive technique using reverse transcription and polymerase chain reaction
      (RT-PCR) has been used to detect circulating tumor cells in the peripheral blood
      of men with prostate cancer. We evaluated the clinical utility of this method for
      staging and monitoring for prostate cancer. Peripheral blood from 39 patients
      with prostate cancer and 7 non-prostate cancer controls was analyzed for prostate
      specific antigen (PSA) messenger RNA (mRNA) using RT-PCR. In 8 among 22 patients
      (36.4%) with clinically localized prostate cancer (T2 or T3), PSA mRNA was
      detected by RT-PCR (RT-PCR positive). Five out of 8 patients (62.5%) with
      regional lymph node and/or bone metastases were RT-PCR positive. The number of
      patients with RT-PCR positive was more frequent in a higher clinical stage. In 22
      patients with clinically localized prostate cancer, 2 of the 9 patients who
      underwent radical prostatectomy had positive surgical margins and both patients
      were RT-PCR positive. Six of the 7 patients with negative surgical margin were RT
      PCR negative. In the 9 cases that had been treated by combined antiandrogen
      blockade for metastatic prostate cancer, 4 patients whose serum PSA level were
      less than 4 ng/ml were all RT-PCR negative. More over 4 of 5 patients with more
      than 4 ng/ml of serum PSA level were RT-PCR positive. All control samples were RT
      PCR negative. This study suggested that this technique using RT-PCR may provide
      useful information in treating patients with prostate cancer, especially for
      candidates for radical prostatectomy. The value of this modality as a prognostic
      factor awaits for further follow-up.

PMID- 10086263
TI  - [Dynamics of prostate-specific antigen as prognostic factors in endocrine
      treatment for prostate cancer].
AB  - Prostate-specific antigen values provide important and unique information about
      prostate cancer to clinicians. However, there is conflicting information about
      the prognostic significance of the dynamics of PSA decline and elevation after
      treatment. To provide further insight into the dynamics of PSA as prognostic
      factors, we herein studied various PSA values as possible prognostic factors in
      93 patients with prostate cancer treated with endocrine therapy. Thirteen (14.0%)
      had stage B tumors, 20 (21.5%) had stage C tumors, and 60 (64.5%) had stage D
      tumors. The overall 5-year survival rate was 41.2%. Relapse was observed in 32
      (34.4%) patients. The influence of pre- and post-treatment PSA (both absolute and
      percentage values) on survival was analyzed. Normalization of PSA value was
      associated with prolonged survival regardless of interval to reach the lowest PSA
      level. The absolute value of PSA at 3 or 6 months following treatment was a
      significant discriminator, while the pre-treatment PSA level and percentage
      values of post-treatment PSA were not. These data show that the PSA nadir and PSA
      value at 3 or 6 months following treatment provide important prognostic
      information.

PMID- 10086264
TI  - [A case of retroperitoneal teratoma in an adult resembling adrenal tumors].
AB  - A retroperitoneal teratoma arising from the vicinity of the upper pole of the
      right kidney in a 61-year-old woman is described. Computed tomographic (CT) scan
      showed well marginated fat density mass with calcification. Magnetic resonance
      imaging (MRI) on T1 weighted image and T2 weighted image showed a high-intensity
      mass above the upper pole of the right kidney. Needle biopsy under computed
      tomography was performed, but no specimen was obtained. The preoperative
      diagnosis was retroperitoneal teratoma or right adrenal myelolipoma. The tumor
      was resected and the histological diagnosis was benign retroperitoneal cystic
      teratoma.

PMID- 10086265
TI  - [Retroperitoneal schwannoma: a case report].
AB  - A 67-year-old man was admitted for a complaint of lumbago. The patient had had
      the three operations for the schwannoma in spinal cord at the Neurosurgical
      Department of our hospital. Magnetic resonance imaging (MRI) revealed a right
      infrarenal tumor by chance. The tumor compressed the right kidney and measured 6
      x 5 cm in size. On the tentative diagnosis of the retroperitoneal tumor, the
      patient was referred to the department of urology in our hospital and the tumor
      was excised. The histological diagnosis of the removed retroperitoneal tumor was
      schwannoma, and was thought to be heterotopic recurrent schwannoma.

PMID- 10086266
TI  - [A case of retroperitoneal hemangiopericytoma].
AB  - We report a case of a huge retroperitoneal tumor in a 67-year-old woman. When the
      patient was taken to another hospital by ambulance, she had lost consciousness
      because of hypertension and hypoglycemia and abdominal CT revealed a huge
      retroperitoneal tumor with deviation of the right kidney and inferior vena cava.
      After further examinations including ultrasonography, MRI and angiography in our
      hospital, the tumor was extirpated. The tumor, 22 x 17 x 10 cm in size and 2,580
      g in weight was diagnosed as hemangiopericytoma histologically. She has remained
      well with no evidence of recurrence for 9 months since the operation.

PMID- 10086267
TI  - [A case of sudden death by pulmonary embolism after angio-embolization of renal
      cell carcinoma extending into the inferior vena cava].
AB  - We report a 42-year-old renal-transplanted man with renal cell carcinoma (RCC) in
      the native kidney. He was admitted with gross hematuria and general fatigue as
      the chief complaint. Ultrasonography, computed tomography, magnetic resonance
      imaging and angiography, revealed a right RCC with intracaval tumor thrombus
      extending to the level of hepatic veins. Since selective renal angiography
      demonstrated a hypervascular tumor, angio-embolization was performed
      preoperatively. However, he died suddenly the next morning despite aggressive
      resuscitative measures. Autopsy revealed bilateral pulmonary arteries obstructed
      by the tumor thrombus. Renal arterial embolization is useful for advanced RCC,
      and side effects are mostly transient and well tolerated by the patients.
      However, indications for angio-embolization should be selected carefully with
      such a fatal case as this patient kept in mind.

PMID- 10086268
TI  - [Spontaneous peripelvic urine extravasation associated with ileocecal cancer: a
      case report].
AB  - A case of spontaneous peripelvic extravasation with ileocecal cancer is reported.
      A 60-year-old man with right flank pain was referred to our department.
      Dripinfusion pyelography showed right peripelvic extravasation. Neither computed
      tomography (CT) nor retrograde pyelography revealed any ureteral stones or
      tumors. Urinary cytology was negative. One month later, right retrograde
      pyelography demonstrated the filling defect in the right ureter, but no stones,
      ureteral tumors or other tumors related to the ureter were detected by CT. An
      exploratory laparotomy was done. We found an ileocecal tumor invading to the
      right ureter and disseminated to the peritoneum. Histological diagnosis was
      mucinous carcinoma.

PMID- 10086269
TI  - [Two cases of bladder tumor producing granulocyte colony stimulating factor].
AB  - Two cases of bladder tumor producing granulocyte colony-stimulating factor (G
      CSF) are reported. The first case was in a 79-year-old female patient. A large
      bladder tumor was diagnosed as right-sided hydronephrosis. The tumor consisted
      mostly of squamous cell carcinoma with a few transitional cells. Total cystectomy
      could not be performed because of direct invasion by the tumor into the pelvis.
      The patient died without aggressive treatment about 7 months after admission. Her
      leukocyte count consistently increased up to 76,200/mm3. The serum G-CSF levels
      were not analyzed. However, immunohistochemical examination revealed a high
      concentration of G-CSF in the tumor specimen. The other case was in an 80-year
      old male patient. The patient, who had refused total cystectomy for bladder tumor
      (transitional cell carcinoma, grade 2, T2N0M0) 2 years earlier, underwent
      ureterocutaneostomy for obstructive renal insufficiency. Total cystectomy was not
      performed at this admission because of tumor invasion into the rectum and his
      advanced age. Radiotherapy was administered. However, he developed ileus caused
      by direct tumor invasion into the ileum. He died about 10 months after the
      urinary diversion. Leukocytosis, which improved transiently following
      radiotherapy, became more severe. The maximum leukocyte count was 49,500/mm3 just
      before death. The serum G-CSF levels during and after radiotherapy were 54 pg/ml
      and < 30 pg/ml, respectively. Immunohistochemical examination revealed the
      presence of G-CSF in the tumor. These findings suggest the production of G-CSF by
      the bladder tumor.

PMID- 10086270
TI  - [Two cases of interstitial cystitis complicated with migraine].
AB  - Two cases of interstitial cystitis complicated with migraine and atopic tendency
      are reported. In the bladder tissue of the two cases, mast cells were increased
      and in one case which was observed with immunohistochemical staining, most of the
      mast cells among muscle layers were chymase-positive mast cells. We considered
      that the degranulation of mast cells was related with the cause of interstitial
      cystitis and migraine.

PMID- 10086271
TI  - Post-traumatic arterial priapism evaluation with color Doppler ultrasonography: a
      case report.
AB  - The patient was a 19-year-old man who was examined due to persistent penile
      erection, which appeared following a blow to the perineal region during work.
      Color Doppler ultrasonography of the corpora cavernosa revealed a cavity in one
      part of the cavernous artery that suggested a blood leak, and a diagnosis of high
      flow type priapism due to trauma was made. Bilateral internal pudendal
      arteriography demonstrated dilation and extravasation in one part of the right
      cavernous artery, then transarterial embolization was performed superselectively
      in the right cavernous artery using an autologous clot. However, 2 weeks after
      treatment, slight penile erection reoccurred. Color Doppler ultrasonography
      revealed reformation of the cavity at the treated lesion, and embolization was
      again performed using a gelatin sponge. Following embolization, the course
      proceeded satisfactorily without any relapse. Color Doppler ultrasonography,
      which is non-invasive and can be easily performed, is considered to be an
      effective means for diagnosis and follow up of arterial high flow priapism.

PMID- 10086272
TI  - [Aggressive angiomyxoma in the scrotum: a case report].
AB  - A case of aggressive angiomyxoma occurring in the scrotum is reported. A 57-year
      old Japanese man presented with a 2-year history of non-tender soft mass in the
      scrotum. Computed tomography and magnetic resonance imaging revealed a well
      defined mass 8 cm in diameter extending from the medial aspect of the left
      ischium. Angiography revealed faint vascularity fed by the left internal pudendal
      artery. Excision was performed by a scrotal approach, and histological
      examination confirmed an aggressive angiomyxoma. The patient showed no recurrence
      at 3 months follow-up.

PMID- 10086273
TI  - [Cancer chemo-endocrine therapy and its cell biological basis].
AB  - The aim of our cell kinetic studies is to better understand the effects of chemo
      endocrine therapy at the cell biological and molecular level. Cancer cell growth
      is characterized by uncontrolled proliferation, resulting in DNA distribution
      pattern in which, at any time, more cells are not G1 phase but in S, G2 and M
      phase of a shortened cycle. In a recent progress, flow cytometry (FCM) has become
      a powerful tool for the quantitative analysis of cell cycle parameters by
      measuring nuclear DNA content in large cell population with high speed. With the
      aid of FCM in earlier work about 60-80% of ovarian cancers were found to contain
      aneuploid cells. Now, multi-parameter FCM linked to a computer is available to
      measure fluorescent intensities not only no base total DNA (Propidium iodide) but
      also A-T (Hoechst 33342) and G-C (Mithramycin) base pairs in solid cancer nuclei.
      Since cisplatinum (CDDP) is the most important drug in the treatment of ovarian
      cancer, we have studied the relationship of CDDP cytotoxicity, pertubations cell
      cycle kinetis and DNA damage in ovarian adenocarcinoma cells in vitro & in vivo.
      We employed both CDDP sensitive cell line (KFt) and resistant cell line (KFr)
      derived from human serous cystoadenocarcinoma of the ovary by Kikuchi et al (JNCI
      1986). Comparing cell kinetic pertubations of experimental cells demonstrates a
      decrease in G1 phase cells concomitant increase in S phase cells. The KFr cells
      had distinctly a shorter S-phase block up to 24 hrs not A-T but G-C preference in
      a quick response followed repairing of DNA damage to 48 hrs. However, some
      fractions of CDDP resistant cell population showed a later onset of G2, M phase
      accumulation. Comparison with the increase in early S phase cells of KFr in
      detailed analysis suggests only those damaged cells that are not killed
      immediately may proceed to G1 phase and start into DNA synthesis in S phase.
      Measurement of labeling index (L. I.) with Bromodeoxyuridine (BrdU) support our
      interpretation of differences between sensitivity and resistance to anti-cancer
      drug. Additionally, we discuss a targeting chemotherapy by coupling cytotoxic
      drugs with estrogen based on increasing DNA damage into apoptosis and interfares
      with DNA repair process.

PMID- 10086274
TI  - Molecular basis of spontaneous regression of neuroblastoma: role of neurotrophic
      signals and genetic abnormalities.
AB  - Neuroblastoma is one of the most common pediatric solid tumors originating from
      the sympathoadrenal lineage of the neural crest. The tumors found in infants very
      frequently regress spontaneously by differentiating and/or undergoing programmed
      cell death, while those in children over one year of age are very aggressive and
      eventually kill the patients. The recent advances in neuroblastoma research have
      revealed that the neurotrophin signals, especially those through nerve growth
      factor and its receptor, TrkA, play an important role in regulating the
      regression of neuroblastoma. The genetic abnormalities such as allelic loss of
      the distal region of chromosome 1p, gain of chromosome 17q21-q25, and MYCN
      amplification, all of which are associated with the tumor aggressiveness, inhibit
      the regression of neuroblastoma. In the regressing tumor cells, caspases are
      induced and surviving, which is mapped to 17q25 and is overexpressed in the
      advanced stage tumors, is down-regulated. Thus, the molecular mechanism of
      spontaneous regression of neuroblastoma is now being unveiled. However, many more
      questions including the developmental machinery to trigger regression still
      remain to be clarified.

PMID- 10086275
TI  - [Apoptosis-inducing and -preventing signal transduction pathways in cultured
      cerebellar granule neurons].
AB  - 1. Cultured cerebellar granule neurons maintained in medium containing 26 mM
      potassium (high K+ or HK+) undergo cell death when switched to medium with 5 mM
      potassium (low K+ or LK+). This low K(+)-induced cell death has typical features
      of apoptosis. The intracellular signaling pathway of low K(+)-induced apoptosis
      has been investigated. 2. Cerebellar granule neurons become committed to undergo
      apoptosis between 2 and 5 h after K+ deprivation, judging from the inability of
      high K+ to rescue them after this time. Although the levels of most mRNAs
      decrease markedly concomitant with commitment, expression of c-jun mRNA increases
      2-3 h after K+ deprivation. Among the family of caspases, a caspase-3-like
      protease is activated within 4 h of lowering the K+ concentration. A caspase-1
      like protease is also activated within 2 h of K+ deprivation. 3. Inhibition of
      phosphatidylinositol 3-kinase (PI3-K) activity by LY294002 or wortmannin also
      induces apoptosis in cerebellar granule neurons. The intracellular signaling
      pathway of LY294002-induced apoptosis has been investigated. The activity of c
      Jun N-terminal kinase (JNK) increases 8 h after addition of LY294002 to high K+
      medium or low K+ medium containing BDNF. Expression of c-Jun protein also
      increases almost simultaneously. 4. The low K(+)-induced apoptosis of cerebellar
      granule neurons is prevented by high K+ (membrane depolarization by high K+),
      BDNF, IGF-1, bFGF or cAMP. The intracellular signaling pathways by which these
      agents prevent low K(+)-induced apoptosis have been investigated. Agents other
      than cAMP prevent apoptosis through PI3-K and a Ser/Thr kinase, Akt/PKB. The
      survival-promoting effect of cAMP does not depend on the PI3-K-Akt pathway.

PMID- 10086276
TI  - Functional roles of microglia in the central nervous system.
AB  - Microglia, a type of perineuronal glial cells in the central nervous system, have
      been suggested to play various important roles in normal and pathologic brains.
      In this article, first, we described the association or roles of activated
      microglia in injury and various brain diseases, and subsequently, summarized
      microglia-derived physiologically active molecules which will affect the neuronal
      survival and neuronal growth, and glial function, and finally, discussed the
      molecular mechanism of microglial activation.

PMID- 10086277
TI  - Roles of neurotrophins on synaptic development and functions in the central
      nervous system.
AB  - Evidence is emerging to suggest that in addition to their "classical"
      neurotrophic involvement in the regulation of the differentiation, maturation and
      survival of neurons, neurotrophins play crucial roles in neural transmission and
      succeeding activity-dependent plasticity of synapses. Here we discuss: 1) the
      regulated synthesis and secretion of neurotrophins in response to neural
      activity, 2) the short- and long-term effects of neurotrophins on neural
      transmission, and 3) the neurotrophin-induced rearrangement of synaptic networks.

PMID- 10086278
TI  - [Anti-proliferative effects of heating on the human prostatic carcinoma cells in
      culture].
AB  - Prostatic cancers are well-known to be sensitive to heat stress. However, the
      mechanism by which the cancer cells are killed by high temperature remains poorly
      understood. The present study was undertaken to determine the anti-proliferative
      effects of heat stress on the prostatic cancer cells in culture. Heat shock at 43
      degrees C inhibited the cell growth of three different prostatic cell lines. Flow
      cytometrical analysis using BrdU and PI showed a decrease in the proportion of
      cells in an S phase, accompanied by cell accumulation in G1 and G2, in both JCA-1
      and PC-3 but not in LNcap. Both JCA-1 and PC-3 presented a strong expression of
      hsp70 at 37 degrees C. The heat shock caused apparent enhancement of the
      expression of hsp70 through the cell cycle. A treatment at 43 degrees C for 8
      hours resulted in not only an apparent increment of positive hsp70 cells, but
      cells with subdiploid DNA content in LNcap. Flow cytometrical analysis by FITC
      labeled Annexin V showed increment of apoptotic cells at 43 degrees C for 8 hours
      in LNcap cells. The results suggest that apoptosis is an important pathway of
      heat-induced killing of these cells. In conclusion, the cell growth of prostatic
      cancers may be affected by the temperature through relationship of the cell cycle
      and hsp70.

PMID- 10086279
TI  - [Anticancer susceptibility test method using general-purpose dissolved oxygen
      meter].
AB  - Drug susceptibility of cell can be rapidly measured by continuously monitoring
      its metabolic changes. We focused on respiration volume as a signal of metabolic
      change, and developed a new dissolved oxygen measuring system which can detect
      respiration volume of cells. The main feature of the system is the use of a new
      type bare oxygen electrode which can easily detect the changing rate of dissolved
      oxygen concentration. In this study, single type electrode was used to evaluate
      this rapid anticancer drug susceptibility test. The result obtained was almost
      equivalent to that with MTT method, which is a conventional method for
      susceptibility test of HL-60 to various kinds of anticancer drugs. We have also
      developed multi-type electrode plate with oxygen electrodes embedded in the
      bottom of 96-well plate, with which clinical evaluation of this method can be
      easily made.

PMID- 10086280
TI  - Intensive therapy: background and development. 1966.

PMID- 10086281
TI  - The assisted respiration unit. 1964.

PMID- 10086282
TI  - pH and acid-base balance measurements. 1987.

PMID- 10086283
TI  - The development of cardiac resuscitation. 1963.

PMID- 10086284
TI  - Cardiac deterioration in shock: I. Its progressive nature. 1964.

PMID- 10086285
TI  - Septic shock. 1964.

PMID- 10086286
TI  - Hyperbaric oxygenation. 1965.

PMID- 10086287
TI  - Pornography, rape, and sex crimes in Japan.

PMID- 10086288
TI  - Police officer attitudes and use of discretion in situations involving the
      mentally ill. The need to narrow the focus.
AB  - Research to date has very effectively highlighted the fact that the mentally ill
      are vulnerable to systematic criminalization. The reasons cited for this range
      from decreasing mental health resources, to restrictive civil commitment
      statutes, to increased numbers of mentally ill citizens in the community as a
      result of deinstitutionalization. However, the research has also shown that the
      presence of a criminalization phenomenon is not yet generalizable. The prevailing
      research emphasizes a macro-level approach, using either archival data or large
      groups of police-citizen contacts without regard for factors intrinsic to the
      police-citizen exchange. This article examined two such variables (police-citizen
      contact type and police officer type) to illustrate the need to narrow the focus
      in the research. We contend that our emphasis moves the criminalization debate
      forward and helps provide a more comprehensive understanding of the interaction
      between the police and the mentally ill. Further, we submit that by controlling
      for these two variables, research findings will more likely be generalizable and
      replicable.

PMID- 10086289
TI  - A comparison between legal and psychiatric statements regarding complaints about
      commitment. A study carried out in a Danish County 1990-1994.
AB  - The object of this retrospective descriptive investigation was to illustrate how
      compulsory committed or detained patients are evaluated in psychiatric statements
      from the hospital, Forensic Medical Council, and court under the Danish Mental
      Health Legislation of 1989. The cases were evaluated using topics and areas
      dealing with the previous and present medical history, legal topics, and legal
      premises. The investigation examines a 5-year period with 40 cases involving 30
      patients, 22 cases of which were presented to the Forensic Medical Council. The
      investigation reveals that in dealing with the medical history only, symptoms and
      treatment are of interest to the court, whereas the legal grounds are of very
      high interest both to the court and the hospital. This investigation raises the
      question as to whether the form of the psychiatric statement faces reality and
      whether the judiciary and psychiatry view the patient from very different angles.
      This requires that the instrument of communication, that is, the psychiatric
      statement, should be accurate.

PMID- 10086290
TI  - Image of psychiatric patients' competency to give informed consent to treatment
      in Japan. I. A factor analytic study.

PMID- 10086291
TI  - Clinical assessment of competency to consent to psychiatric hospitalization.

PMID- 10086292
TI  - The medical model of mental illness. Its application to the insanity defense.

PMID- 10086293
TI  - Workers' compensation and stress. Gender and access to compensation.

PMID- 10086294
TI  - Personality disorders, psychopathy, and crime in a Norwegian prison population.

PMID- 10086295
TI  - Accuracy and confidence in clinical assessment of psychiatric inpatients risk of
      violence.

PMID- 10086296
TI  - [Indications for and selection of dialysis methods in acute and chronic renal
      failure including continuous methods].

PMID- 10086297
TI  - [Dialysis approach for hemo- and peritoneal dialysis].

PMID- 10086298
TI  - [Adequate dialysis treatment in hemodialysis and peritoneal dialysis patients].

PMID- 10086299
TI  - [Biocompatibility of renal replacement therapy].

PMID- 10086300
TI  - [Nutrition in acute and chronic kidney replacement therapy].

PMID- 10086301
TI  - [Long-term management of dialysis patients. I. Hypertension and anemia].

PMID- 10086302
TI  - [Long-term management of dialysis patients. II. Beta 2-microglobulin associated
      amyloidosis and acquired cystic kidney disease].

PMID- 10086303
TI  - [Renal osteopathy (ROP)].

PMID- 10086304
TI  - [Gait disorders].

PMID- 10086305
TI  - [Fever and lumbalgia in a 22-year-old patient. Vertebral osteomyelitis mit
      epidural abscess].

PMID- 10086306
TI  - [Bone pain in the last pregnancy trimester].

PMID- 10086307
TI  - [Increased CK, LDH and alpha-HBDH without myoglobin or CK-MB increase].

PMID- 10086308
TI  - [ACC in liver failure].

PMID- 10086309
TI  - [Possibilities for basic therapy of Bechterew disease].

PMID- 10086310
TI  - [Diagnosis of latent hyperthyroidism].

PMID- 10086311
TI  - [Various HMG-CoA reductase inhibitors].

PMID- 10086312
TI  - [Inhalational anticholinergic versus inhaled beta-mimetic drugs in COPD].

PMID- 10086313
TI  - [Can milk also be harmful?].

PMID- 10086314
TI  - [Risk of infection by needle-stick injury].

PMID- 10086315
TI  - [Successful treatment of multiple sclerosis with beta-interferon].

PMID- 10086316
TI  - Molecular mechanisms of Fyn-tyrosine kinase for regulating mammalian behaviors
      and ethanol sensitivity.
AB  - Mice lacking Fyn, a Src-related non-receptor tyrosine kinase, show impairment of
      various behaviors, such as spatial learning, suckling, emotional behaviors, and
      ethanol sensitivity. These mice also display both morphological defects and
      impairment of synaptic function. Fyn is highly expressed in the mammalian CNS
      from embryonic day 8.5 to adulthood. Pharmacological and electrophysiological
      analyses of mice lacking Fyn reveal gamma-aminobutyric acid and glutamatergic
      defects. We propose here the hypothesis that these defects are caused separately
      by developmental disorganization and impairment of synapse function by a deficit
      in Fyn. Regarding the glutamatergic defect, in particular, after ethanol
      administration the N-methyl-D-aspartate (NMDA)-dependent function is recovered by
      Fyn, paralleled with tyrosine phosphorylation of NMDA receptor 2B subtype. Thus,
      modulation of the NMDA receptor function by Fyn may have a significant role in
      building and regulating sophisticated neural circuits and behavior. In addition,
      the cadherin-related neural receptor (CNR) family is isolated by binding activity
      for Fyn. The CNR-Fyn complex will also open a new angle for gaining insight into
      the molecular mechanisms for regulating mammalian behavior.

PMID- 10086317
TI  - ADP-induced platelet aggregation and inhibition of adenylyl cyclase activity
      stimulated by prostaglandins: signal transduction mechanisms.
AB  - ADP is the oldest and one of the most important agonists of platelet activation.
      ADP induces platelet shape change, exposure of fibrinogen binding sites,
      aggregation, and influx and intracellular mobilization of Ca2+. ADP-induced
      platelet aggregation is important for maintaining normal hemostasis, but aberrant
      platelet aggregation manifests itself pathophysiologically in myocardial
      ischemia, stroke, and atherosclerosis. Another important aspect of ADP-induced
      platelet activation is the ability of ADP to antagonize adenylyl cyclase
      activated by prostaglandins. ADP-induced inhibition of the stimulated adenylyl
      cyclase activity does not appear to play a role in ADP-induced platelet
      aggregation in vitro or in vivo. It is believed that a single ADP receptor
      mediates the above two ADP-induced platelet responses in platelets. The ADP
      receptor mediating ADP-induced platelet aggregation and inhibition of the
      stimulated adenylyl cyclase activity has not been purified. Therefore, the nature
      of molecular mechanisms underlying the two seemingly unrelated ADP-induced
      platelet responses remains either unclear or less well understood. The purpose of
      this commentary is to examine and make suggestions concerning the role of
      phospholipases and G-proteins in the molecular mechanisms of signal transduction
      underlying the two ADP-induced platelet responses. It is hoped that such
      discussion would stimulate thinking and invite future debates on this subject,
      and energize investigators in their efforts to advance our knowledge of the
      details of the molecular mechanisms of ADP-induced platelet activation.

PMID- 10086318
TI  - Decreased cisplatin damage-dependent DNA synthesis in cellular extracts of
      mismatch repair deficient cells.
AB  - The proficiency of both nucleotide excision repair (NER) and DNA mismatch repair
      (MMR) influences cellular sensitivity to cisplatin (cis
      diamminedichloroplatinum). To gain further insight into how MMR may influence
      platinum drug sensitivity, the effect of loss of MMR on repair synthesis was
      measured in vitro by a commonly used method that relies on whole-cell extracts to
      drive [alpha-32P]dATP incorporation into cisplatin-damaged plasmid DNA. Extracts
      evaluated include those from cells with or without functional hMLH1 (HCT116+ch2
      versus HCT116+ch3, respectively) and hMSH2 (HEC59 versus HEC59+ch2,
      respectively). Loss of MMR in the HCT116 system was associated with a 2.8-fold
      reduction in cisplatin damage-specific DNA synthesis, whereas it was associated
      with a 3.0-fold reduction in the HEC59 system, suggesting that a decrease in the
      ability to repair cisplatin-damaged DNA accompanies loss of MMR. An in vitro DNA
      excision assay that utilized a substrate containing a site-specific cisplatin
      adduct was performed. Using this highly NER-specific assay, no significant
      difference was apparent between the extracts derived from NER-proficient versus 
      deficient cells. These and other data lead us to suggest that the increase in
      apparent repair synthesis in platinum-damaged plasmids by extracts from MMR
      proficient versus -deficient cellular extracts may reflect a distinct and
      possibly adverse DNA synthetic process rather than productive NER.

PMID- 10086319
TI  - Effects of tiadenol and di-(2-ethylhexyl)phthalate on the metabolism of
      phosphatidylcholine and phosphatidylethanolamine in the liver of rats: comparison
      with clofibric acid.
AB  - Metabolic changes induced by 2,2'-(decamethylenedithio)diethanol (tiadenol) and
      di-(2-ethylhexyl)phthalate (DEHP) in the biosynthesis of phosphatidylcholine
      (PtdCho) and phosphatidylethanolamine (PtdEtn) in rat liver were compared with
      changes induced by p-chlorophenoxyisobutyric acid (clofibric acid). Treatment of
      rats with either tiadenol or DEHP increased the hepatic contents of PtdCho and
      PtdEtn, as was observed with clofibric acid treatment. The administration of
      tiadenol, DEHP, or clofibric acid slightly, but significantly, increased, in
      common, the activity of CTP:phosphocholine cytidylyltransferase, a key enzyme for
      the synthesis de novo of PtdCho, and suppressed the activity of PtdEtn N
      methyltransferase. With regard to the enzymes involved in the synthesis of
      PtdEtn, the three peroxisome proliferators enhanced the activity of
      phosphatidylserine (PtdSer) decarboxylase and markedly decreased the activity of
      CTP:phosphoethanolamine cytidylyltransferase. Treatment of rats with the three
      compounds markedly increased, in common, the content and the proportion of the
      molecular species of PtdCho containing oleic acid (18:1), but considerably
      decreased the proportion of the molecular species of PtdCho containing linoleic
      acid (18:2) in the liver, resulting in a striking decrease in the concentration
      of the molecular species of PtdCho containing 18:2 in the serum. The present
      study suggests that the administration of peroxisome proliferators to rats
      increases the contents of hepatic PtdCho and PtdEtn for hepatomegaly and
      proliferation of organelles by the same mechanism, irrespective of their chemical
      structures.

PMID- 10086320
TI  - Selectivity of the molecular chaperone-specific immunosuppressive agent 15
      deoxyspergualin: modulation of Hsc70 ATPase activity without compromising DnaJ
      chaperone interactions.
AB  - The immunosuppressive and cytostatic agent 15-deoxyspergualin (DSG) binds to the
      Hsc70 class of molecular chaperones with a K(D) = 4 microM. Because Hsc70s
      represent a diverse group of cellular effectors and because Hsc70 function
      frequently requires a DnaJ molecular chaperone, the specificity of DSG for
      different Hsc70s and the ability of DSG to block the productive interaction
      between an Hsc70 and its DnaJ partner were examined. DSG stimulated the ATPase
      activity of a mammalian and yeast cytosolic Hsc70 from 20 to 40%, but was unable
      to elicit such a response in a homologous Hsc70, Binding Protein (BiP), that
      resides in the lumen of the endoplasmic reticulum. In addition, the DnaJ
      stimulated Hsc70 ATPase activity and the DnaJ-mediated release of an unfolded
      polypeptide from an Hsc70 were unaffected by DSG. These results indicate that
      Hsc70s exhibit substrate selectivity for DSG and that DSG does not compromise
      Hsc70 functions that require DnaJs. Thus, the immunosuppressive and cytostatic
      effects of DSG may be specific for a subset of cellular Hsc70s and confined to
      DnaJ-independent Hsc70-mediated activities.

PMID- 10086321
TI  - Site-specific DNA methylation and apoptosis: induction by diabetogenic
      streptozotocin.
AB  - Streptozotocin (STZ) is known to induce insulin-dependent diabetes mellitus via
      DNA damage in experimental animals. The mechanism of induction of DNA damage by
      STZ was investigated in vitro, using a human cell line and 32P-labeled DNA
      fragments isolated from human genes. STZ induced cellular DNA damage and
      apoptosis, and frequently initiated DNA modification at guanines, especially at
      the middle guanine in runs of three and at the guanine at the 3'-end of runs of
      two guanines, similar to N-methyl-N-nitrosourea, a typical methylating agent.
      Scavengers for reactive oxygen species or nitric oxide did not inhibit the
      induction of DNA damage by STZ. On the other hand, damage induction was inhibited
      by sodium acetate and sodium chloride, which can reduce the reactivity of
      methylating agents to DNA via the sodium cation. These results suggest that STZ
      induces DNA damage by methylation of guanines via methyl cations. This alkylation
      may be responsible for triggering apoptosis, and subsequently diabetes.

PMID- 10086322
TI  - Mechanism of anti-HIV activity of succinylated human serum albumin.
AB  - In the present study, we described the interaction of succinylated human serum
      albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1
      gp120 and in detail with the third variable domain of gp120 (V3 loop). To this
      end, different assay formats were tested in which gp120- and V3-related peptides
      were presented in various configurations in order to investigate the effect of
      the conformational structure of the V3 loop on the interaction with negatively
      charged albumins. When gp120 presented via a lectin was used, it was observed
      that Suc-HSA bound to native gp120. The binding site appeared to be located at or
      near the thrombin digestion site (GPGRAF sequence) in the V3 loop of gp120, since
      the cleavage of the loop resulted in decreased binding of Suc-HSA. In addition,
      Suc-HSA was able to protect the V3 region of gp120 from cleaving with thrombin.
      In contrast, significant binding of Suc-HSA to V3 loop or gp120 peptides was not
      observed when both were presented in a fluid phase system, suggesting the
      involvement of a monovalent-low affinity binding of Suc-HSA. Using overlapping
      peptides delineating the whole V3 loop immobilized to CNBr-Sepharose, we noticed
      that the interaction of the V3 loop with Suc-HSA was predominantly induced by
      electrostatic interactions between positively charged linearized peptide
      fragments and Suc-HSA and was positively influenced by the presence of
      hydrophobic amino in the V3 loop fragments as well. Moreover, the highest
      affinity site was located at sites near the GPGRAF sequence. These observations
      add to the evidence, collected earlier, that Suc-HSA interferes at the level of
      virus entry, independent of interaction with the CD4 receptor. Since the recently
      discovered chemokine receptors are negatively charged, we can hypothesize that
      Suc-HSA is able to prevent the positively charged V3 loop from interacting with
      these types of receptors, thereby inhibiting virus entry.

PMID- 10086323
TI  - Defects of tyrosine289phenylalanine mutation on binding and functional properties
      of the human tachykinin NK2 receptor stably expressed in chinese hamster ovary
      cells.
AB  - A point mutation was made at position 289 in the transmembrane segment 7 of the
      human tachykinin NK2 receptor to yield a tyrosine/phenylalanine (Tyr/Phe)
      substitution. Chinese hamster ovary cells stably transfected with the wild-type
      or Tyr289Phe mutant NK2 receptor both bound neurokinin A (NKA) and the synthetic
      NK2 receptor-selective agonists, GR 64349 and [betaAla8]NKA(4-10), with high and
      even affinities. Neurokinin B (NKB) and substance P (SP) also displayed sizeable
      binding affinities, albeit with lower affinity as compared to NKA. In a
      functional assay (production of inositol-1,4,5-trisphosphate, IP3), NKA, GR
      64349, and [betaAla8]INKA(4-10) stimulated IP3 accumulation via the wild-type and
      mutant receptors with similar potencies. On the other hand, NKB and SP exhibited
      a dramatic reduction in their agonist efficacies at the mutant receptor, NKB
      acting as a partial agonist (maximum effect = 50% of the response to NKA) and SP
      being totally inactive. The results obtained with phenoxybenzamine inactivation
      experiments indicated that a large and similar receptor reserve existed for both
      the wild-type and the mutant receptor. SP, which displayed sizeable binding
      affinity for the mutant receptor but did not stimulate IP3 accumulation,
      antagonized the agonist effect of NKA. The antagonist action of SP at the mutant
      NK2 receptor cannot be ascribed to receptor internalization. The Tyr/Phe
      replacement at position 289 markedly reduced the binding affinity and antagonist
      potency of the non-peptide ligand, SR 48968, without affecting the binding
      affinity and antagonist potency of the bicyclic peptide antagonist MEN 11420. The
      results indicate that the hydroxyl radical function of Tyr289 in transmembrane
      segment 7 of the human NK2 receptor is, directly or indirectly, involved in
      stimulus transduction when the NK2 receptor is occupied by NKB or SP, but not
      when using NKA or NK2 receptor-selective agonists.

PMID- 10086324
TI  - Effect of chronic chloroquine administration on iron loading in the liver and
      reticuloendothelial system and on oxidative responses by the alveolar
      macrophages.
AB  - The ability of chloroquine to alter iron loading in the liver, spleen, and
      alveolar macrophages was investigated in iron-loaded or -depleted rats.
      Chloroquine significantly reduced incorporation of iron into the liver, spleen,
      and alveolar macrophages of animals loaded in vivo with iron dextran. The ability
      of these macrophages to respond to oxidative stress was assayed by their capacity
      to release reactive nitrogen intermediates after lipopolysaccharide (LPS)
      stimulation. A significant reduction in nitrite release was observed in primary
      cultures of macrophages isolated from chloroquine/iron dextran-administered rats
      in comparison to macrophages lavaged from rats iron-loaded alone. Macrophages
      isolated from iron-deficient rats showed a significant increase in nitrite after
      LPS stimulation, whereas nitrite release in the macrophages lavaged from the rats
      which had also received chloroquine during the iron depletion regime was much
      lower. These results indicate that the use of agents which decrease the iron
      content and diminish the oxidative response of the cell to altered iron status
      may be of therapeutic value in patients with iron loading, particularly of the
      reticuloendothelial system.

PMID- 10086325
TI  - Efficacy of isatin analogues as antagonists of rat brain and heart atrial
      natriuretic peptide receptors coupled to particulate guanylyl cyclase.
AB  - Isatin is an endogenous indole and an inhibitor of atrial natriuretic peptide
      (ANP) receptors coupled with particulate guanylyl cyclase (GC). In this study,
      several isatin analogues were tested as inhibitors of ANP-stimulated GC in rat
      brain and heart membranes. None of these analogues affected activity in the
      absence of ANP, or stimulated ANP-induced activity. In both tissues, some 5
      substituted isatins (5-hydroxyisatin, 5-methylisatin, and 5-aminoisatin)
      exhibited more effective inhibitory activity than isatin itself, with IC50 values
      in the range 1.3-20 microM. The efficacy of other analogues varied and was not
      consistent between the two tissues, raising the possibility of receptor
      heterogeneity and relative selectivity of inhibition. Some substituted isatins
      may have a role as pharmacological tools for investigating the physiological
      roles of natriuretic peptides and their receptors.

PMID- 10086326
TI  - Irreversible inhibition of epidermal growth factor receptor tyrosine kinase with
      in vivo activity by N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide (CL
      387,785).
AB  - It has been shown previously that 4-anilino quinazolines compete with the ability
      of ATP to bind the epidermal growth factor receptor (EGF-R), inhibit EGF
      stimulated autophosphorylation of tyrosine residues in EGF-R, and block EGF
      mediated growth. Since millimolar concentrations of ATP in cells could reduce the
      efficacy of 4-anilino quinazolines in cells and the activity of these compounds
      would not be sustained once they were removed from the body, we reasoned that
      irreversible inhibitors of EGF-R might improve the activity of this series of
      compounds in animals. Molecular modeling of the EGF-R kinase domain was used to
      design irreversible inhibitors. We herein describe one such inhibitor: N-[4-[(3
      bromophenyl)amino]-6-quinazolinyl]2-butynamide, known as CL-387,785. This
      compound covalently bound to EGF-R. It also specifically inhibited kinase
      activity of the protein (IC50 = 370+/-120 pM), blocked EGF-stimulated
      autophosphorylation of the receptor in cells (ic50 approximately 5 nM), inhibited
      cell proliferation (IC50 = 31-125 nM) primarily in a cytostatic manner in cell
      lines that overexpress EGF-R or c-erbB-2, and profoundly blocked the growth of a
      tumor that overexpresses EGF-R in nude mice (when given orally at 80 mg/kg/day
      for 10 days, daily). We conclude that CL-387,785 is useful for studying the
      interaction of small molecules with EGF-R and may have clinical utility.

PMID- 10086327
TI  - Lowering of trichosanthin immunogenicity by site-specific coupling to dextran.
AB  - Trichosanthin is a type I ribosome-inactivating protein possessing a broad
      spectrum of biological and pharmacological activities. Therapeutic use of this
      compound is hampered by its immunogenicity. It was shown earlier that coupling of
      dextran to trichosanthin can increase plasma half-life and reduce antigenicity.
      However, the site where dextran attaches to trichosanthin cannot be controlled;
      ideally, it should be at or near the antigenic determinant. The present study
      attempted to couple dextran to trichosanthin at a potential antigenic site. By
      site-directed mutagenesis, two sites, R29 and K173, were replaced by cysteine,
      and dextran was coupled to the newly created cysteine residues. The dextran
      trichosanthin complex retained 50% of abortifacient activity and had a mean
      residence time in rats 27-fold longer than natural trichosanthin. Acute
      hypersensitivity reaction in guinea pigs was reduced greatly after coupling of
      K173C (a trichosanthin mutant with lysine-173 replaced by cysteine) to dextran.
      Compared with natural trichosanthin, dextran-K173C had a decrease in IgG and IgE
      response, whereas the coupling of R29C (a trichosanthin mutant with arginine-29
      replaced by cysteine) to dextran did not show significant reduction of
      immunogenicity. This suggests that K173 but not R29 is located at or near an
      antigenic determinant. This study has demonstrated an alternative approach for
      mapping of antigenic determinants. The information obtained is also useful in
      producing an improved trichosanthin derivative for therapeutic use.

PMID- 10086328
TI  - No ethnic difference between Caucasian and Japanese hepatic samples in the
      expression frequency of CYP3A5 and CYP3A7 proteins.
AB  - Ethnic differences in the pharmacokinetics of nifedipine, a substrate of CYP3A,
      and in CYP3A7 expression have been reported. The aim of the present study was to
      measure the protein levels of CYP3A4, CYP3A5, and CYP3A7 and nifedipine oxidation
      activity in hepatic microsomes from 15 Caucasian and 15 Japanese patients for
      comparison between the two ethnic groups. Nifedipine oxidation activity and
      CYP3A4 protein level were well correlated. No significant difference between
      Caucasian and Japanese microsomal samples was found in nifedipine oxidation
      activity or in the CYP3A4 protein level. CYP3A5 was detected in 6 of 15 Caucasian
      samples and in 5 of 15 Japanese samples, but no ethnic difference was found in
      either the frequency of expression or its protein level. CYP3A7 was found in 10
      of 15 Caucasian samples and in 14 of 15 Japanese samples. Although the estimated
      CYP3A7 protein level was higher in the Japanese than in the Caucasian samples,
      its protein level was much lower than that of CYP3A4. These results imply that
      the contribution of CYP3A5 or CYP3A7 to the purported Caucasian-Japanese ethnic
      difference in the overall CYP3A activity seems to be small.

PMID- 10086329
TI  - Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory
      cytokine expression in RAW 264.7 macrophages.
AB  - The beneficial effects of moderate red wine consumption have been attributed, in
      part, to the presence of antioxidant components. Oxidant stress is an activating
      stimulus for the NF (nuclear factor)-KB/Rel family of transcription factors,
      which have binding sites in the promoter regions of many genes involved in
      inflammatory and immune responses. The effect of lipopolysaccharide (LPS)
      stimulated activation of NF-KB and the subsequent production of tumor necrosis
      factor alpha (TNF-alpha) and NO was determined in the macrophage cell line RAW
      264.7. Unexpectedly, the wine polyphenolics quercetin and resveratrol and the
      antioxidant N-acetylcysteine (NAC) did not inhibit LPS-induced activation of the
      NF-KB complex p50/65, as determined by mobility shift. Quercetin inhibited LPS
      induced p50/50. Northern blot analysis indicated that quercetin (0.1 and 0.2 mM)
      inhibited LPS-dependent production of inducible nitric oxide synthase (iNOS) mRNA
      and decreased NO release, as measured by the Griess reaction. This flavonoid had
      no effect on LPS-induced TNF-alpha mRNA, but decreased LPS-stimulated TNF-alpha
      release, as measured by ELISA. Resveratrol (0.05 and 0.1 mM)
      posttranscriptionally decreased LPS-induced nitrite release. It increased basal
      levels of TNF-alpha mRNA and protein and enhanced LPS-induced TNF-alpha mRNA and
      cytokine release. Our results do not support the view that wine antioxidants
      inhibit LPS-induced NF-KB activation but instead that they have a more selective
      action on genes activated by LPS.

PMID- 10086330
TI  - Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.
AB  - Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and
      proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in
      rats. Although high doses of IL-2 are administered to cancer patients, the effect
      on human CYPs has not yet been determined. Patients with hepatic metastases from
      colon or rectum carcinomas were randomly allocated to various daily doses of
      human recombinant IL-2 (from 0 to 12.10(6) units/m(2)). IL-2 was infused from day
      7 to day 3 before hepatectomy and the conservation of a non-tumorous liver
      fragment in liquid nitrogen. Hepatic CYPs and monooxygenase activities were not
      significantly decreased in 5 patients receiving daily doses of 3 or 6 10(6) IL-2
      units/m2, compared to 7 patients who did not receive IL-2. In contrast, in 6
      patients receiving daily doses of 9 or 12 x 10(6) IL-2 units/m2, the mean values
      for immunoreactive CYP1A2, CYP2C, CYP2E1, and CYP3A4 were 37, 45, 60 and 39%,
      respectively, of those in controls; total CYP was significantly decreased by 34%,
      methoxyresorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%.
      These observations suggest that high doses of IL-2 may decrease total CYP and
      monooxygenase activities in man.

PMID- 10086331
TI  - Protective effect of gamma-glutamylcysteinylethyl ester on dysfunction of the
      selenium-deficient rat heart.
AB  - We investigated the protective effect of intracellular GSH against cardiac
      dysfunction in selenium (Se)-deficient neonatal rats and cultured fetal rat
      myocytes. A Se-deficient diet with or without daily subcutaneous injections of
      gamma-glutamylcysteinylethyl ester (gammay-GCE) (a membrane-permeating GSH
      precursor) was given to rats from gestation day 4 via the dam to postnatal day
      14. Se deficiency induced a 62% incidence of electrocardiographic abnormalities
      such as sinus arrhythmias or extrasystole, a 63% reduction in dP/dt in the left
      ventricle, and an increase in thiobarbituric acid reacting substances (TBARS),
      but no ultrastructural cardiac lesions were observed. Administration of gamma-GCE
      increased the intracellular GSH concentration ([GSH]i) of both neonatal rat
      hearts and cultured fetal rat cardiac myocytes. gamma-GCE-like sodium selenite
      prevented the cardiac dysfunction and the TBARS increment. gamma-GCE also
      prevented H2O2 toxicity in the cultured myocytes. The Vmax, but not the Km, for
      GSH of Se-dependent GSH peroxidase (Se-Gpx) activity in Se-deficient rat heart
      homogenates was one-third that of normal rat heart homogenates. Although gamma
      GCE did not affect the Se-Gpx Vmax and Km for GSH, it did induce a substantial
      and significant increase in [GSH]i, which was postulated to increase the velocity
      of H2O2 decomposition by Se-Gpx activity 1.6-fold. These data suggest that the
      increase in [GSH]i may have played a role in preventing the TBARS increase and
      cardiac dysfunction in Se-deficient rats.

PMID- 10086332
TI  - Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts.
AB  - Apoptosis is accompanied by the activation of a number of apoptotic proteases
      (caspases) which selectively cleave specific cellular substrates. Caspases
      themselves are zymogens which are activated by proteolysis. It is widely believed
      that 'initiator' caspases are recruited to and activated within apoptotic
      signalling complexes, and then cleave and activate downstream 'effector'
      caspases. While activation of the effector caspase, caspase-3, has indeed been
      observed as distal to activation of several different initiator caspases,
      evidence for a further downstream proteolytic cascade is limited. In particular,
      there is little evidence that cellular levels of caspase-3 that are activated via
      one pathway are sufficient to cleave and activate other initiator caspases. To
      address this issue, the ability of caspase-3, activated upon addition to
      cytosolic extracts of cytochrome c, to cause cleavage of caspase-2 was
      investigated. It was demonstrated that cleavage of caspase-2 follows, and is
      dependent upon, activation of caspase-3. Moreover, the activation of both
      caspases was inhibited by Bcl-2. Together, these data indicate that Bcl-2 can
      protect cells from apoptosis by acting at a point downstream from release of
      mitochondrial cytochrome c, thereby preventing a caspase-3 dependent proteolytic
      cascade.

PMID- 10086333
TI  - Posttranslational regulation of the retinoblastoma gene family member p107 by
      calpain protease.
AB  - The retinoblastoma protein plays a critical role in regulating the G1/S
      transition. Less is known about the function and regulation of the homologous
      pocket protein p107. Here we present evidence for the posttranslational
      regulation of p107 by the Ca2+-activated protease calpain. Three negative growth
      regulators, the HMG-CoA reductase inhibitor lovastatin, the antimetabolite 5
      fluorouracil, and the cyclic nucleotide dibutyryl cAMP were found to induce cell
      type-specific loss of p107 protein which was reversible by the calpain inhibitor
      leucyl-leucyl-norleucinal but not by the serine protease inhibitor
      phenylmethylsulfonylfluoride, caspase inhibitors, or lactacystin, a specific
      inhibitor of the 26S proteasome. Purified calpain induced Ca2+-dependent p107
      degradation in cell lysates. Transient expression of the specific calpain
      inhibitor calpastatin blocked the loss of p107 protein in lovastatin-treated
      cells, and the half-life of p107 was markedly lengthened in lovastatian-treated
      cells stably transfected with a calpastatin expression vector versus cells
      transfected with vector alone. The data presented here demonstrate down
      regulation of p107 protein in response to various antiproliferative signals, and
      implicate calpain in p107 posttranslational regulation.

PMID- 10086334
TI  - Overexpression of D-type cyclins, E2F-1, SV40 large T antigen and HPV16 E7 rescue
      cell cycle arrest of tsBN462 cells caused by the CCG1/TAF(II)250 mutation.
AB  - tsBN462 cells, which have a point mutation in CCG1/TAF(II)250, a component of
      TFIID complex, arrest in G1 at the nonpermissive temperature of 39.5 degrees C.
      Overexpression of D-type cyclins rescued the cell cycle arrest of tsBN462 cells,
      suggesting that the cell cycle arrest was through Rb. Consistent with this,
      overexpression of E2F-1, whose function is repressed by the hypophosphorylated
      form of Rb, also rescued the cell cycle arrest. Moreover, expression of the viral
      oncoproteins SV40 large T antigen and HPV16 E7, which both bind Rb and inactivate
      its function, rescued the cell cycle arrest, whereas HPV16 E6 did not. Mutation
      of the Rb-binding motif in E7 abrogated its ability to rescue the cell cycle
      arrest. Expression of exogenous cyclin D1, SV40 large T antigen or
      CCG1/TAF(II)250 increased cyclin A expression at 39.5 degrees C. Coexpression of
      HPV16 E7 and adenovirus E1b19K, which blocks apoptosis, rescued the proliferation
      of tsBN462 cells at 38.5 degrees C. To investigate the mechanism underlying the
      lack of cyclin D1 expression, deletion analysis of cyclin D1 promoter was
      performed. The 0.15 kbp cyclin D1 core promoter region, which lacks any
      transcription factor binding motifs, still exhibited a temperature-sensitive
      phenotype in tsBN462 cells suggesting that CCG1/TAF(II)250 is critical for the
      function of the cyclin D1 core promoter.

PMID- 10086335
TI  - Differential contribution of the ERK and JNK mitogen-activated protein kinase
      cascades to Ras transformation of HT1080 fibrosarcoma and DLD-1 colon carcinoma
      cells.
AB  - Although an important contribution of ERK and JNK mitogen-activated protein
      kinase (MAPK) activation in Ras transformation of rodent fibroblasts has been
      determined, their role in mediating oncogenic Ras transformation of human tumor
      cells remains to be established. We have utilized the human HT1080 fibrosarcoma
      and DLD-1 colon carcinoma cell lines, which contain endogenous mutated and
      oncogenic N- and K-ras alleles, respectively, to address this role. Study of
      these cells is advantageous over Ras-transformed rodent model cell systems for
      two key reasons. First, the ras mutations occurred naturally in the progression
      of the tumors from which the cell lines were derived, rather than due to
      overexpression of an exogenously introduced gene. Second, although these tumor
      cells possess defects in multiple genetic loci, it has been established that
      mutated Ras contributes significantly to the transformed phenotype of these
      cells. Clonal variant lines of HT1080 and DLD-1 have been isolated which have
      lost the oncogenic ras allele and exhibit a corresponding impairment in growth
      transformation in vitro and in vivo. We found that upregulation of Raf/MEK/ERK
      and JNK correlated with expression of oncogenic Ras in HT1080, but not DLD-1
      cells. Furthermore, inhibition of ERK activation in parental HT1080 cells caused
      the same changes in cell morphology and actin stress fiber organization seen with
      loss of expression of activated N-Ras(61K). Thus, we suggest that constitutive
      activation of the Raf/MEK/ERK and JNK pathways is necessary for Ras-induced
      transformation of HT1080 but not DLD-1 cells. These results emphasize that cell
      type differences exist in the signaling pathways by which oncogenic Ras causes
      transformation.

PMID- 10086336
TI  - Anchorage-dependent expression of cyclin A in primary cells requires a negative
      DNA regulatory element and a functional Rb.
AB  - Many cells, when cultured in suspension, fail to express cyclin A, a regulatory
      component of cell cycle kinases cdc2 and cdk2 and as a consequence, do not enter
      S phase. However, many cell type-specific differences are disclosed between not
      only normal and transformed cells, but also between cell lines whose
      proliferation is strictly anchorage-dependent. These apparent discrepancies are
      seen in established cell lines most probably because of adaptative events that
      have occurred during cell culture. We have therefore used primary cells to
      understand how cyclin A transcription is controlled by cell anchorage properties.
      To this aim, we have used embryonic fibroblasts from either wild type, Rb(-/-) or
      p107(-/-)/p130(-/-) mice and tested the effect of an ectopic expression of Rb
      mutants. In the experiments reported here, we show that anchorage-dependent
      expression of cyclin A (i) is reflected by the in vivo occupancy of a negative
      DNA regulatory element previously shown to be instrumental in the down regulation
      of cyclin A transcription in quiescent cells (Cell Cycle Responsive Element:
      CCRE) (ii) requires a functional Rb but neither p107 nor p130 (iii) mutation of
      the CCRE abolishes both adhesion-dependent regulation and response to Rb.

PMID- 10086337
TI  - Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of
      matrix adhesion.
AB  - The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells
      from a variety of apoptotic injuries. In several instances, the anti-apoptotic
      effect of the wild type IGF-IR is more evident under conditions of anchorage
      independence than in cells in monolayer cultures. We have investigated IGF-IR
      signaling in cells in anoikis, a form of apoptosis that occurs when cells are
      denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo
      fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival
      is dependent on the concentration of IGF-I and a sufficient number of functional
      IGF-I receptors. In this model, IGF-I protection correlates best with ras
      activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases
      seem to play a lesser, alternative role.

PMID- 10086338
TI  - Cooperation between SMAD and NF-kappaB in growth factor regulated type VII
      collagen gene expression.
AB  - We have previously demonstrated that transforming growth factor-beta (TGF-beta)
      and pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha)
      or interleukin-1beta, synergistically enhance the expression of type VII collagen
      gene (COL7A1) in human dermal fibroblasts in culture (Mauviel et al., 1994).
      Recently, we identified a SMAD-containing complex, rapidly induced by TGF-beta
      and binding the region [-496/-444] of the COL7A1 promoter, responsible for COL7A1
      gene transactivation (Vindevoghel et al., 1998a). In this report, we demonstrate
      that TGF-beta and TNF-alpha response elements are distinct entities within the
      COL7A1 promoter. In particular, we demonstrate that the TNF-alpha effect is
      mediated by NF-kappaB1/RelA (p50/p65) and RelA/RelA (p65/p65) NF-kappaB complexes
      binding the TNF-alpha response element (TaRE) located in the region [-252/-230],
      with RelA acting as the transcriptional activator. Finally, we provide definitive
      evidence for the role of both TGF-beta and TNF-alpha response elements as
      enhancer sequences, functioning in the context of a heterologous promoter in an
      additive manner in response to TGF-beta and TNF-alpha. This study provides the
      first identification of a functional interaction between the two immediate-early
      transcription factors, SMAD and NF-kappaB, to activate the expression of an
      extracellular matrix-related gene, COL7A1.

PMID- 10086339
TI  - The cyclin B2 promoter depends on NF-Y, a trimer whose CCAAT-binding activity is
      cell-cycle regulated.
AB  - Cyclin B2 is a regulator of p34cdc2 kinase, involved in G2/M progression of the
      cell cycle, whose gene is strictly regulated at the transcriptional level in
      cycling cells. The mouse promoter was cloned and three conserved CCAAT boxes were
      found. In this study, we analysed the mechanisms leading to activation of the
      cyclin B2 CCAAT boxes: a combination of (i) genomic footprinting, (ii)
      transfections with single, double and triple mutants, (iii) EMSAs with nuclear
      extracts, antibodies and NF-Y recombinant proteins and (iv) transfections with an
      NF-YA dominant negative mutant established the positive role of the three CCAAT
      sequences and proved that NF-Y plays a crucial role in their activation. NF-Y, an
      ubiquitous trimer containing histone fold subunits, activates several other
      promoters regulated during the cell cycle. To analyse the levels of NF-Y subunits
      in the different phases of the cycle, we separated MEL cells by elutriation,
      obtaining fractions >80% pure. The mRNA and protein levels of the histone-fold
      containing NF-YB and NF-YC were invariant, whereas the NF-YA protein, but not its
      mRNA, was maximal in mid-S and decreased in G2/M. EMSA confirmed that the CCAAT
      binding activity followed the amount of NF-YA, indicating that this subunit is
      limiting within the NF-Y complex, and suggesting that post-transcriptional
      mechanisms regulate NF-YA levels. Our results support a model whereby fine tuning
      of this activator is important for phase-specific transcription of CCAAT
      containing promoters.

PMID- 10086340
TI  - cbl-b inhibits epidermal growth factor receptor signaling.
AB  - The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR) was
      studied and compared with c-cbl. We demonstrate in vivo, that cbl-b, like c-cbl,
      is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl
      proteins can bind to the Grb2 adaptor protein. To investigate the functional role
      of cbl proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells
      overexpressing the EGFR (32D/EGFR). This cell line is absolutely dependent on
      exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b
      showed markedly inhibited growth in EGF compared to c-cbl transfectants and
      vector controls. This growth inhibition by cbl-b was the result of a dramatic
      increase in the number of cells undergoing apoptosis. Consistent with this
      finding, cbl-b overexpression markedly decreased the amplitude and duration of
      AKT activation upon EGF stimulation compared to either vector controls or c-cbl
      overexpressing cells. In addition, the duration of EGF mediated MAP kinase and
      Jun kinase activation in cells overexpressing cbl-b is shortened. These data
      demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl
      have distinct roles in EGF mediated signaling.

PMID- 10086341
TI  - Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein
      expressed in proliferating cells.
AB  - Shc adaptor proteins play a role in linking activated cell surface receptors to
      the Ras signaling pathway in response to receptor mediated tyrosine kinase
      activation. While the function of Shc in the activation of the Ras pathway via
      binding to Grb2 has been well characterized, it is becoming increasingly apparent
      that Shc participates in additional signaling pathways through interactions with
      other cytoplasmic proteins. Using the yeast two-hybrid system, we have identified
      a unique Shc binding protein designated PAL (Protein expressed in Activated
      Lymphocytes) with no similarity to other known proteins. mPAL binds specifically
      to the Shc SH2 domain and unlike previously described Shc SH2 domain-protein
      interactions, the association of mPAL and Shc is phosphotyrosine-independent.
      Both mPAL RNA and protein expression are restricted to tissues containing
      actively dividing cells and proliferating cells in culture. mPAL expression is
      induced upon growth factor stimulation and is down-regulated upon growth
      inhibition. This pattern, and timing of mPAL expression and its association with
      the Shc adaptor molecule suggests a role for this protein in signaling pathways
      governing cell cycle progression.

PMID- 10086342
TI  - Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and
      tumour-derived cell lines.
AB  - We identified CAVEOLIN-1 as a candidate for a tumour suppressor gene mapping to
      human chromosome 7q31.1. A number of studies suggest that caveolin could function
      as a tumour suppressor. Expression of caveolin, and in turn the number of
      caveolae within a cell, are inversely correlated with the transforming ability of
      numerous oncoproteins, including H-ras, v-abl, and bcr-abl, and caveolin is a
      major transformation-dependent substrate of v-src. Heterologous expression of
      caveolin has been shown to abrogate anchorage-independent growth and induce
      apoptosis in transformed fibroblasts and also to suppress anchorage-independent
      growth in human mammary carcinoma cells. We have analysed the status and
      expression of the human CAVEOLIN-1 gene in primary tumours and tumour-derived
      cell lines. We found no evidence for mutation of CAVEOLIN-1 in human cancers.
      Additionally, we found that while the first two exons of CAVEOLIN-1 are
      associated with a CpG island, this is not methylated in either primary tumours or
      in tumour-derived cell lines in which Caveolin-1 expression is low or
      undetectable. The level of expression of Caveolin-1 does not correlate with loss
      of heterozygosity at the CAVEOLIN-1 locus in these same cell lines. Contrary to
      other published studies, we have shown that CAVEOLIN-1 is not expressed in normal
      breast ductal epithelial cells in vivo. CAVEOLIN-1 is however highly expressed in
      breast myoepithelial cells and its expression is retained in tumours derived from
      breast myoepithelium. Together our data refute a role for CAVEOLIN-1 as a breast
      tumour suppressor gene in vivo.

PMID- 10086343
TI  - Involvement of retinoblastoma (Rb) and E2F transcription factors during
      photodynamic therapy of human epidermoid carcinoma cells A431.
AB  - Photodynamic therapy (PDT), a promising new therapeutic modality for the
      management of a variety of solid malignancies and many non-malignant diseases, is
      a bimodal therapy using a porphyrin based photosensitizing chemical and visible
      light. The proper understanding of the mechanism of PDT-mediated cancer cell-kill
      may result in improving the efficacy of this treatment modality. Earlier we have
      shown (Proc. Natl. Acad. Sci. USA; 95: 6977-6982, 1998) that silicon
      phthalocyanine (Pc4)-PDT results in an induction of the cyclin kinase inhibitor
      WAF1/CIP1/p21 which, by inhibiting cyclins (E and D1) and cyclin dependent
      kinases (cdk2 and cdk6), results in a G0/G1-phase arrest followed by apoptosis in
      human epidermoid carcinoma cells A431. We have also demonstrated the generation
      of nitric oxide during PDT-mediated apoptosis (Cancer Res.; 58: 1785-1788, 1998).
      Retinoblastoma (pRb) and E2F family transcription factors are important proteins,
      which regulate the G1-->S transition in the cell cycle. Here, we provide evidence
      for the involvement of pRb-E2F/DP machinery as an important contributor of PDT
      mediated cell cycle arrest and apoptosis. Western blot analysis demonstrated a
      decrease in the hyper-phosphorylated form of pRb at 3, 6 and 12 h post-PDT with a
      relative increase in hypo-phosphorylated pRb. Western blot analysis also revealed
      that PDT-caused decrease in phosphorylation of pRb occurs at serine-780. The
      ELISA data demonstrated a time dependent accumulation of hypo-phosphorylated pRb
      by PDT. This response was accompanied with down-regulation in the protein
      expression of all five E2F (1-5) family transcription factors, and their
      heterodimeric partners DP1 and DP2. These results suggest that Pc4-PDT of A431
      cells results in a down regulation of hyper-phosphorylated pRb protein with a
      relative increase in hypo-phosphorylated pRb that, in turn, compromises with the
      availability of free E2F. We suggest that these events result in a stoppage of
      the cell cycle progression at G1-->S transition thereby leading to a G0/G1 phase
      arrest and a subsequent apoptotic cell death. These data provide an evidence for
      the involvement of pRb-E2F/DP machinery in PDT-mediated cell cycle arrest leading
      to apoptosis.

PMID- 10086344
TI  - Mutations of c-kit JM domain are found in a minority of human gastrointestinal
      stromal tumors.
AB  - The c-kit gene encodes a transmembrane receptor kinase (KIT) which is expressed
      in the majority of human gastrointestinal stromal tumors (GISTs), a subtype of
      gastrointestinal mesenchymal neoplasms. A previous study identified mutations in
      the juxtamembrane (JM) domain of c-kit in five of six GISTs (Science 279: 577,
      1998). To better define the frequency and spectrum of c-kit gene mutations in
      mesenchymal neoplasms of the GI tract that had been characterized for KIT protein
      expression, we examined archived tissue samples for mutations in the JM domain by
      PCR amplification and DNA sequencing. c-kit JM domain mutations were found in
      nine of 56 mesenchymal tumors (46 GISTs, eight leiomyomas, two leiomyosarcomas)
      and occurred exclusively in GISTs (21%). Seven of the nine mutations consisted of
      intragenic deletions of one to 19 codons. There was one insertion mutation that
      added 12 codons and one missense mutation (Val560Asp). None of the mutations
      disrupted the downstream reading frame of the gene. The single missense mutation
      (Val560Asp) is very similar to the only other missense mutation reported in GISTs
      (Val599Asp). Of the 46 GISTs, 43 were strongly positive for KIT protein
      expression and negative for diffuse expression of desmin. Neither KIT expression
      nor gene mutations were found in gastrointestinal leiomyomas or leiomyosarcomas.
      We conclude that mutation of the c-kit JM domain does not occur in
      gastrointestinal mesenchymal neoplasms with well developed-smooth muscle
      differentiation, and is restricted to GISTs. However, since these mutations are
      only found in a minority of GISTs, further investigation into the mechanisms of c
      kit gene activation in this group of neoplasms is warranted.

PMID- 10086345
TI  - Differential expression assay of chromosome arm 8p genes identifies Frizzled
      related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate
      breast cancer genes.
AB  - Deletions and amplifications are frequent alterations of the short arm of
      chromosome 8 associated with various types of cancers, including breast cancers.
      This indicates the likely presence of tumor suppressor genes and oncogenes. In
      the present study, we have used the expressed sequence tag (EST) map of 8p11-21
      to assemble a set of available cDNAs representing genes from this region. DNA
      arrays were prepared for expression analysis and search for genes potentially
      involved in breast cancer. Underexpresion in tumoral breast cells (versus normal
      breast) was observed for 15 transcripts. Among these, the Frizzled-related gene
      FRP1/FRZB, was turned off in 78% of breast carcinomas, suggesting that the lack
      of its product may be associated with malignant transformation. Overexpression in
      tumoral breast cells was observed for 13 genes. The FGFR1 gene, that encodes a
      tyrosine kinase receptor for members of the fibroblast growth factor family, was
      identified as a good candidate for one amplification unit. Taken together, our
      results demonstrate that such a strategy can rapidly identify genes with an
      altered pattern of expression and provide candidate genes for malignancies.

PMID- 10086346
TI  - Biologists make plea to NIH to invest in supercomputer centre.

PMID- 10086347
TI  - US Nobel winners back stem-cell research.

PMID- 10086348
TI  - Japan's transplant law 'is too stringent'...but the pill may be legalized at
      last.

PMID- 10086349
TI  - Food scientist in GMO row defends 'premature' warning.

PMID- 10086350
TI  - Call for research and education to tackle 'environmental injustice'.

PMID- 10086351
TI  - It's time to 'out' the selfish researchers.

PMID- 10086353
TI  - Retroshuffling the genomic deck.

PMID- 10086352
TI  - Moving protein heads for breakdown.

PMID- 10086354
TI  - Genetic flexibility of plant chloroplasts.

PMID- 10086355
TI  - The mahogany protein is a receptor involved in suppression of obesity.
AB  - Genetic studies have shown that mutations within the mahogany locus suppress the
      pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant.
      Here we identify the mahogany gene and its product; this study, to our knowledge,
      represents the first positional cloning of a suppressor gene in the mouse.
      Expression of the mahogany gene is broad; however, in situ hybridization analysis
      emphasizes the importance of its expression in the ventromedial hypothalamic
      nucleus, a region that is intimately involved in the regulation of body weight
      and feeding. We present new genetic studies that indicate that the mahogany locus
      does not suppress the obese phenotype of the melanocortin-4-receptor null allele
      or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However,
      mahogany can suppress diet-induced obesity, the mechanism of which is likely to
      have implications for therapeutic intervention in common human obesity. The amino
      acid sequence of the mahogany protein suggests that it is a large, single
      transmembrane-domain receptor-like molecule, with a short cytoplasmic tail
      containing a site that is conserved between Caenorhabditis elegans and mammals.
      We propose two potential, alternative modes of action for mahogany: one draws
      parallels with the mechanism of action of low-affinity proteoglycan receptors
      such as fibroblast growth factor and transforming growth factor-beta, and the
      other suggests that mahogany itself is a signalling receptor.

PMID- 10086356
TI  - The mouse mahogany locus encodes a transmembrane form of human attractin.
AB  - Agouti protein and agouti-related protein are homologous paracrine signalling
      molecules that normally regulate hair colour and body weight, respectively, by
      antagonizing signalling through melanocortin receptors. Expression of Agouti is
      normally limited to the skin, but rare alleles from which Agouti is expressed
      ubiquitously, such as lethal yellow, have pleiotropic effects that include a
      yellow coat, obesity, increased linear growth, and immune defects. The mahogany
      (mg) mutation suppresses the effects of lethal yellow on pigmentation and body
      weight, and results of our previous genetic studies place mg downstream of
      transcription of Agouti but upstream of melanocortin receptors. Here we use
      positional cloning to identify a candidate gene for mahogany, Mgca. The predicted
      protein encoded by Mgca is a 1,428-amino-acid, single-transmembrane-domain
      protein that is expressed in many tissues, including pigment cells and the
      hypothalamus. The extracellular domain of the Mgca protein is the orthologue of
      human attractin, a circulating molecule produced by activated T cells that has
      been implicated in immune-cell interactions. These observations provide new
      insight into the regulation of energy metabolism and indicate a molecular basis
      for crosstalk between melanocortin-receptor signalling and immune function.

PMID- 10086357
TI  - A protective role for protease-activated receptors in the airways.
AB  - The protection of cells in the upper intestine against digestion by pancreatic
      trypsin depends on the prostanoid prostaglandin E2 (PGE2) and is mediated by
      protease-activated receptors in the epithelium. As the airway epithelium is
      morphologically similar and also expresses one of these receptors, PAR2, and is a
      major source of PGE2, we reasoned that bronchial epithelial PAR2 might also
      participate in prostanoid-dependent cytoprotection in the airways. Here we show
      that activation of PAR2, which co-localizes immunohistochemically with
      trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations
      from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product
      from the epithelium. This physiological protective response in isolated airways
      also occurred in anaesthetized rats, where activation of PAR2 caused a marked and
      prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the
      response to trypsin recovered rapidly by mechanisms dependent on de novo
      synthesis and trafficking of proteins. Our results indicate that trypsin released
      from the epithelium can initiate powerful bronchoprotection in the airways by
      activation of epithelial PAR2.

PMID- 10086358
TI  - Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by
      Jab1.
AB  - The proliferation of mammalian cells is under strict control, and the cyclin
      dependent-kinase inhibitory protein p27Kip1 is an essential participant in this
      regulation both in vitro and in vivo. Although mutations in p27Kip1 are rarely
      found in human tumours, reduced expression of the protein correlates well with
      poor survival among patients with breast or colorectal carcinomas, suggesting
      that disruption of the p27Kip1 regulatory mechanisms contributes to neoplasia.
      The abundance of p27Kip1 in the cell is determined either at or after
      translation, for example as a result of phosphorylation by cyclinE/Cdk2
      complexes, degradation by the ubiquitin/proteasome pathway, sequestration by
      unknown Myc-inducible proteins, binding to cyclinD/Cdk4 complexes, or
      inactivation by the viral E1A oncoprotein. We have found that a mouse 38K protein
      (p38) encoded by the Jab1 gene interacts specifically with p27Kip1 and show here
      that overexpression of p38 in mammalian cells causes the translocation of p27Kip1
      from the nucleus to the cytoplasm, decreasing the amount of p27Kip1 in the cell
      by accelerating its degradation. Ectopic expression of p38 in mouse fibroblasts
      partially overcomes p27Kip1-mediated arrest in the G1 phase of the cell cycle and
      markedly reduces their dependence on serum. Our findings indicate that p38
      functions as a negative regulator of p27Kip1 by promoting its degradation.

PMID- 10086359
TI  - CBP-independent activation of CREM and CREB by the LIM-only protein ACT.
AB  - Transcriptional activation by CREB and CREM requires phosphorylation of a serine
      residue within the activation domain (Ser 133 in CREB; Ser 117 in CREM) which as
      a result interacts with the coactivator CBP. The activator CREM is highly
      expressed in male germ cells and is required for post-meiotic gene expression.
      Using a two-hybrid screen, we have isolated a testis-derived complementary DNA
      encoding a protein that we term ACT (for activator of CREM in testis), a LIM-only
      protein which specifically associates with CREM. ACT is expressed coordinately
      with CREM in a tissue- and developmentally regulated manner. It strongly
      stimulates CREM transcriptional activity in yeast and mammalian cells and
      contains an intrinsic activation function. As ACT bypasses the classical
      requirements for activation, namely phosphorylation of Ser 117 and interaction
      with CBP, it represents a new route for transcriptional activation by CREM and
      CREB. ACT may define a previously undiscovered class of tissue-specific
      coactivators whose function could be specific for distinct cellular
      differentiation programmes.

PMID- 10086360
TI  - Gene therapy and the germline.

PMID- 10086361
TI  - Calcineurin and human heart failure.

PMID- 10086362
TI  - Chinese genetics and ethics.

PMID- 10086364
TI  - Bruntland makes waves in her first six months at the WHO.

PMID- 10086365
TI  - Novo Nordisk invests in academic diabetes research.

PMID- 10086366
TI  - No-consent trials raise concern.

PMID- 10086367
TI  - South Africa plans home-grown HIV vaccine.

PMID- 10086368
TI  - Roslin Institute upset by human cloning suggestions.

PMID- 10086369
TI  - NCI defends research involving minority groups.

PMID- 10086370
TI  - In utero gene therapy: the case against.

PMID- 10086371
TI  - In utero gene therapy: the case for.

PMID- 10086372
TI  - Brain stem cells change their identity.

PMID- 10086373
TI  - Mesenchymal stem cells: no longer second class marrow citizens.

PMID- 10086374
TI  - New pieces to the prostate cancer puzzle.

PMID- 10086375
TI  - Etiologies of cardiomyopathy and heart failure.

PMID- 10086376
TI  - Fas counter-attack--the best form of tumor defense?

PMID- 10086377
TI  - Implicating PARP and NAD+ depletion in type I diabetes.

PMID- 10086378
TI  - Shakespeare in love--with NMDA receptors?

PMID- 10086379
TI  - Malaria from Africa blows hot and cold.

PMID- 10086380
TI  - NOS: modulator, not mediator of cardiac performance.

PMID- 10086381
TI  - Modulation of oncogenic potential by alternative gene use in human prostate
      cancer.
AB  - Only a small percentage of primary prostate cancers have genetic changes. In
      contrast, nearly 90% of clinically significant human prostate cancers seems to
      express high levels of the nuclear phosphoprotein pp32 by in situ hybridization.
      Because pp32 inhibits oncogene-mediated transformation, we investigated its
      paradoxical expression in cancer by comparing the sequence and function of pp32
      species from paired benign prostate tissue and adjacent prostatic carcinoma from
      three patients. Here we demonstrate that pp32 is expressed in benign prostatic
      tissue, but pp32r1 and pp32r2, closely-related genes located on different
      chromosomes, are expressed in prostate cancer. Although pp32 is a tumor
      suppressor, pp32r1 and pp32r2 are tumorigenic. Alternative use of the pp32,
      pp32r1 and pp32r2 genes may modulate the oncogenic potential of human prostate
      cancer.

PMID- 10086382
TI  - A mechanism for hormone-independent prostate cancer through modulation of
      androgen receptor signaling by the HER-2/neu tyrosine kinase.
AB  - Prostate cancer progresses from a hormone-sensitive, androgen-dependent stage to
      a hormone-refractory, androgen-independent tumor. The androgen receptor pathway
      functions in these androgen-independent tumors despite anti-androgen therapy. In
      our LAPC-4 prostate cancer model, androgen-independent sublines expressed higher
      levels of the HER-2/neu receptor tyrosine kinase than their androgen-dependent
      counterparts. Forced overexpression of HER-2/neu in androgen-dependent prostate
      cancer cells allowed ligand-independent growth. HER-2/neu activated the androgen
      receptor pathway in the absence of ligand and synergized with low levels of
      androgen to 'superactivate' the pathway. By modulating the response to low doses
      of androgen, a tyrosine kinase receptor can restore androgen receptor function to
      prostate cancer cells, a finding directly related to the clinical progression of
      prostate cancer.

PMID- 10086383
TI  - Reduced expression of neural cell adhesion molecule induces metastatic
      dissemination of pancreatic beta tumor cells.
AB  - As in the development of many human cancers, in a transgenic mouse model of beta
      cell carcinogenesis (Rip1Tag2), expression of neural cell adhesion molecule
      (NCAM) changes from the 120-kDa isoform in normal tissue to the 140/180-kDa
      isoforms in tumors. NCAM-deficient RiplTag2 mice, generated by crossing Rip1Tag2
      mice with NCAM knockout mice, develop metastases, a tumor stage that is not seen
      in normal Rip1Tag2 mice. In contrast, overexpression of NCAM 120 in NCAM
      deficient Rip1Tag2 mice prevents tumor metastasis. The results indicate that the
      loss of NCAM-mediated cell adhesion is one rate-limiting step in the actual
      metastatic dissemination of beta tumor cells.

PMID- 10086384
TI  - Fas ligand (CD95 ligand) controls angiogenesis beneath the retina.
AB  - A principal cause of blindness is subretinal neovascularization associated with
      age-related macular degeneration. Excised neovascular membranes from patients
      with age-related macular degeneration demonstrated a pattern of Fas+ new vessels
      in the center of the vascular complex, surrounded by FasL+ retinal pigment
      epithelial cells. In a murine model, Fas (CD95)-deficient (Ipr) and FasL
      defective (gld) mice had a significantly increased incidence of
      neovascularization compared with normal mice. Furthermore, in gld mice there is
      massive subretinal neovascularization with uncontrolled growth of vessels. We
      found that cultured choroidal endothelial cells were induced to undergo apoptosis
      by retinal pigment epithelial cells through a Fas-FasL interaction. In addition,
      antibody against Fas prevented vascular tube formation of choroidal endothelial
      cells derived from the eye in a three-dimensional in vitro assay. Thus, FasL
      expressed on retinal pigment epithelial cells may control the growth and
      development of new subretinal vessels that can damage vision.

PMID- 10086385
TI  - Neuroprotection by a caspase inhibitor in acute bacterial meningitis.
AB  - Half of the survivors of bacterial meningitis experience motor deficits,
      seizures, hearing loss or cognitive impairment, despite adequate bacterial
      killing by antibiotics. We demonstrate that the broad-spectrum caspase inhibitor
      N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevented
      hippocampal neuronal cell death and white blood cell influx into the
      cerebrospinal fluid compartment in experimental pneumococcal meningitis.
      Hippocampal neuronal death was due to apoptosis derived from the inflammatory
      response in the cerebrospinal fluid. Apoptosis was induced in vitro in human
      neurons by inflamed cerebrospinal fluid and was blocked by z-VAD-fmk. As
      apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors
      might provide a new therapeutic option directed specifically at reducing brain
      damage.

PMID- 10086386
TI  - Fusion of monocytes and macrophages with HIV-1 correlates with biochemical
      properties of CXCR4 and CCR5.
AB  - Human macrophages can be infected more efficiently by M-tropic than by T-tropic
      HIV-1 strains, despite surface expression of both CXCR4 and CCR5 co-receptors.
      Western blot analyses of total cell extracts and surface proteins from multiple
      sets of monocytes and macrophages demonstrated substantial differences between
      CXCR4 molecules. CXCR4 was mainly a monomer in monocytes, but was mainly a
      species of higher molecular weight (90 kDa) on the surface of macrophages. CCR5
      was monomeric in both cell types. A constitutive association between CD4 and the
      co-receptors was seen in monocytes and macrophages. However, CD4 co-precipitated
      with CCR5 and CXCR4 monomers, but not with the high-molecular-weight forms of
      CXCR4, indicating that the high-molecular-weight CXCR4 species in macrophages are
      not available for association with CD4, which may contribute to the inefficient
      entry of T-tropic strains into mature macrophages.

PMID- 10086387
TI  - Transplantability and therapeutic effects of bone marrow-derived mesenchymal
      cells in children with osteogenesis imperfecta.
AB  - In principle, transplantation of mesenchymal progenitor cells would attenuate or
      possibly correct genetic disorders of bone, cartilage and muscle, but clinical
      support for this concept is lacking. Here we describe the initial results of
      allogeneic bone marrow transplantation in three children with osteogenesis
      imperfecta, a genetic disorder in which osteoblasts produce defective type I
      collagen, leading to osteopenia, multiple fractures, severe bony deformities and
      considerably shortened stature. Three months after osteoblast engraftment (1.5
      2.0% donor cells), representative specimens of trabecular bone showed histologic
      changes indicative of new dense bone formation. All patients had increases in
      total body bone mineral content ranging from 21 to 29 grams (median, 28),
      compared with predicted values of 0 to 4 grams (median, 0) for healthy children
      with similar changes in weight. These improvements were associated with increases
      in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic
      bone marrow transplantation can lead to engraftment of functional mesenchymal
      progenitor cells, indicating the feasibility of this strategy in the treatment of
      osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as
      well.

PMID- 10086388
TI  - Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic
      beta-cell destruction and diabetes development induced by streptozocin.
AB  - Human type 1 diabetes results from the selective destruction of insulin-producing
      pancreatic beta cells during islet inflammation. Cytokines and reactive radicals
      released during this process contribute to beta-cell death. Here we show that
      mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP-/- mice)
      are completely resistant to the development of diabetes induced by the beta-cell
      toxin streptozocin. The mice remained normoglycemic and maintained normal levels
      of total pancreatic insulin content and normal islet ultrastructure. Cultivated
      PARP-/- islet cells resisted streptozocin-induced lysis and maintained
      intracellular NAD+ levels. Our results identify NAD+ depletion caused by PARP
      activation as the dominant metabolic event in islet-cell destruction, and provide
      information for the development of strategies to prevent the progression or
      manifestation of the disease in individuals at risk of developing type 1
      diabetes.

PMID- 10086389
TI  - Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption
      in an acquired cardiomyopathy.
AB  - Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, but the
      mechanism of this pathology is unknown. Mutations in cytoskeletal proteins such
      as dystrophin cause hereditary dilated cardiomyopathy, but it is unclear if
      similar mechanisms underlie acquired forms of heart failure. We demonstrate here
      that purified Coxsackievirus protease 2A cleaves dystrophin in vitro as predicted
      by computer analysis. Dystrophin is also cleaved during Coxsackievirus infection
      of cultured myocytes and in infected mouse hearts, leading to impaired dystrophin
      function. In vivo, dystrophin and the dystrophin-associated glycoproteins alpha
      sarcoglycan and beta-dystroglycan are morphologically disrupted in infected
      myocytes. We suggest a molecular mechanism through which enteroviral infection
      contributes to the pathogenesis of acquired forms of dilated cardiomyopathy.

PMID- 10086390
TI  - The pathogenesis of familial hypertrophic cardiomyopathy: early and evolving
      effects from an alpha-cardiac myosin heavy chain missense mutation.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder resulting from
      mutations in genes encoding sarcomeric proteins. This typically induces
      hyperdynamic ejection, impaired relaxation, delayed early filling, myocyte
      disarray and fibrosis, and increased chamber end-systolic stiffness. To better
      understand the disease pathogenesis, early (primary) abnormalities must be
      distinguished from evolving responses to the genetic defect. We did in vivo
      analysis using a mouse model of FHC with an Arg403Gln alpha-cardiac myosin heavy
      chain missense mutation, and used newly developed methods for assessing in situ
      pressure-volume relations. Hearts of young mutant mice (6 weeks old), which show
      no chamber morphologic or gross histologic abnormalities, had altered contraction
      kinetics, with considerably delayed pressure relaxation and chamber filling, yet
      accelerated systolic pressure rise. Older mutant mice (20 weeks old), which
      develop fiber disarray and fibrosis, had diastolic and systolic kinetic changes
      similar to if not slightly less than those of younger mice. However, the hearts
      of older mutant mice also showed hyperdynamic contraction, with increased end
      systolic chamber stiffness, outflow tract pressure gradients and a lower cardiac
      index due to reduced chamber filling; all 'hallmarks' of human disease. These
      data provide new insights into the temporal evolution of FHC. Such data may help
      direct new therapeutic strategies to diminish disease progression.

PMID- 10086391
TI  - Muscarinic and beta-adrenergic regulation of heart rate, force of contraction and
      calcium current is preserved in mice lacking endothelial nitric oxide synthase.
AB  - Nitric oxide (NO) is an ubiquitous signaling molecule produced from L-arginine by
      NO synthase (NOS). In the vasculature, NO mediates parasympathetic endothelium
      dependent vasodilation. NO may also mediate the parasympathetic control of
      myocardial function. This is supported by the observations that NOS3, the
      endothelial constitutive NOS, is expressed in normal cardiac myocytes from
      rodents and human, and NOS and/or guanylyl cyclase inhibitors antagonize the
      effect of muscarinic agonists on heart rate, atrio-ventricular conduction,
      contractility and L-type calcium current. Here we examine the autonomic
      regulation of the heart in genetically engineered mice deficient in NOS3 (NOS3
      KO). We show that the chronotropic and inotropic responses to both beta
      adrenergic and muscarinic agonists were unaltered in isolated cardiac tissue
      preparations from NOS3-KO mice, although these mice have a defective
      parasympathetic regulation of vascular tone. Similarly, beta-adrenergic
      stimulation and muscarinic inhibition of the calcium current did not differ in
      cardiac myocytes from NOS3-KO mice and those from wild-type mice. RT-PCR did not
      demonstrate upregulation of other NOS isoforms. Similarly, Gi/Go proteins and
      muscarinic receptor density were unaltered. These data refute the idea that NOS3
      is obligatory for the normal autonomic control of cardiac muscle function.

PMID- 10086392
TI  - The absence of p53 accelerates atherosclerosis by increasing cell proliferation
      in vivo.
AB  - The tumor suppressor protein p53 is an essential molecule in cell proliferation
      and programmed cell death (apoptosis), and has been postulated to play a
      principal part in the development of atherosclerosis. We have examined the effect
      of p53 inactivation on atherogenesis in apoE-knockout mice, an animal model for
      atherosclerosis. We found that, compared with p53+/+/apoE-/- mice, p53-/-/apoE-/-
      mice developed considerably accelerated aortic atherosclerosis in the presence of
      a similar serum cholesterol in response to a high-fat diet. Furthermore, the
      atherosclerotic lesions in p53-/-/apoE-/- mice had a significant (approximately
      280%) increase in cell proliferation rate and an insignificant (approximately
      180%) increase in apoptosis compared with those in p53+/+/apoE-/- mice. Our
      observations indicate that the role of p53 in atherosclerotic lesion development
      might be associated with its function in cell replication control, and that p53
      independent mechanisms can mediate the apoptotic response in atherosclerosis.

PMID- 10086393
TI  - Immunity to non-cerebral severe malaria is acquired after one or two infections.
AB  - In areas of stable transmission, clinical immunity to mild malaria is acquired
      slowly, so it is not usually effective until early adolescence. Life-threatening
      disease is, however, restricted to a much younger age group, indicating that
      resistance to the severe clinical consequences of infection is acquired more
      quickly. Understanding how rapidly immunity develops to severe malaria is
      essential, as severe malaria should be the primary target of intervention
      strategies, and predicting the result of interventions that reduce host exposure
      will require consideration of these dynamics. Severe disease in childhood is less
      frequent in areas where transmission is the greatest. One explanation for this is
      that infants experience increased exposure to infection while they are protected
      from disease, possibly by maternal antibody. They therefore emerge from this
      period of clinical protection with considerably more immunity than those who
      experience lower transmission intensities. Here we use this data, assuming a
      period of clinical protection, to estimate the number of prior infections needed
      to reduce the risk of severe disease to negligible levels. Contrary to
      expectations, one or two successful infective bites seem to be all that is
      necessary across a broad range of transmission intensities.

PMID- 10086394
TI  - CCR5- and CXCR4-tropic HIV-1 are equally cytopathic for their T-cell targets in
      human lymphoid tissue.
AB  - A rapid decline in T-cell counts and the progression to AIDS is often associated
      with a switch from CCR5-tropic (R5) HIV-1 to CXCR4-tropic (X4) HIV-1 or R5/X4 HIV
      1 variants. Experimental infection with R5 HIV-1 causes less T-cell depletion
      than infection with X4 or R5/X4 variants in T-cell cultures, in ex vivo infected
      human lymphoid tissue and in SCID/hu mice, despite similar replication levels.
      Experimental genetic changes in those sequences in gp120 that transform R5 HIV-1
      variants into otherwise isogenic X4 viruses make them highly cytopathic. Thus, it
      is now believed that R5 variants are less cytopathic for T cells than are X4
      variants. However, it is not known why CCR5-mediated HIV-1 infection does not
      lead to a massive CD4+ T-cell depletion, as occurs in CXCR4-mediated HIV-1
      infection. Here we demonstrate that R5 HIV-1 isolates are indeed highly
      cytopathic, but only for CCR5+/CD4+ T cells. Because these cells constitute only
      a small fraction of CD4+ T cells, their depletion does not substantially change
      the total CD4+ T-cell count. These results may explain why the clinical stage of
      HIV disease correlates with viral tropism.

PMID- 10086395
TI  - Neuroprotective effects of creatine in a transgenic animal model of amyotrophic
      lateral sclerosis.
AB  - Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial
      swelling and vacuolization are among the earliest pathologic features found in
      two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1
      mutations. Mice with the G93A human SOD1 mutation have altered electron transport
      enzymes, and expression of the mutant enzyme in vitro results in a loss of
      mitochondrial membrane potential and elevated cytosolic calcium concentration.
      Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell
      death. If this is true, then buffering intracellular energy levels could exert
      neuroprotective effects. Creatine kinase and its substrates creatine and
      phosphocreatine constitute an intricate cellular energy buffering and transport
      system connecting sites of energy production (mitochondria) with sites of energy
      consumption, and creatine administration stabilizes the mitochondrial creatine
      kinase and inhibits opening of the mitochondrial transition pore. We found that
      oral administration of creatine produced a dose-dependent improvement in motor
      performance and extended survival in G93A transgenic mice, and it protected mice
      from loss of both motor neurons and substantia nigra neurons at 120 days of age.
      Creatine administration protected G93A transgenic mice from increases in
      biochemical indices of oxidative damage. Therefore, creatine administration may
      be a new therapeutic strategy for ALS.

PMID- 10086396
TI  - Monitoring simultaneous subcellular events in vitro by means of coherent
      multiprobe fluorescence.

PMID- 10086397
TI  - Pediatric medical student education: new and deja vu.

PMID- 10086398
TI  - Preventing adolescent health-risk behaviors by strengthening protection during
      childhood.
AB  - OBJECTIVE: To examine the long-term effects of an intervention combining teacher
      training, parent education, and social competence training for children during
      the elementary grades on adolescent health-risk behaviors at age 18 years.
      DESIGN: Nonrandomized controlled trial with follow-up 6 years after intervention.
      SETTING: Public elementary schools serving high-crime areas in Seattle, Wash.
      PARTICIPANTS: Of the fifth-grade students enrolled in participating schools, 643
      (76%) were given written parental consent for the longitudinal study and 598
      (93%) were followed up and interviewed at age 18 years. INTERVENTIONS: A full
      intervention provided in grades 1 through 6 of 5 days of in-service training for
      teachers each intervention year, developmentally appropriate parenting classes
      offered to parents when children were in grades 1 through 3 and 5 through 6, and
      developmentally adjusted social competence training for children in grades 1 and
      6. A late intervention, provided in grades 5 and 6 only, paralleled the full
      intervention at these grades. MAIN OUTCOME MEASURES: Self-reported violent and
      nonviolent crime, substance use, sexual activity, pregnancy, bonding to school,
      school achievement, grade repetition and school dropout, suspension and/or
      expulsion, and school misbehavior; delinquency charges from court records; grade
      point average; California Achievement Test scores: and disciplinary action
      reports from school records. RESULTS: Fewer students receiving full intervention
      than control students reported violent delinquent acts (48.3% vs 59.7%; P=.04),
      heavy drinking (15.4% vs 25.6%; P=.04), sexual intercourse (72.1% vs 83.0%;
      P=.02), having multiple sex partners (49.7% vs 61.5%; P=.04), and pregnancy or
      causing pregnancy (17.1% vs 26.4%; P=.06) by age 18 years. The full intervention
      student group reported more commitment (P=.03) and attachment (P=.006) to school,
      better academic achievement (P=.01), and less school misbehavior (P=.02) than
      control students. Late intervention in grades 5 and 6 only did not significantly
      affect health-risk behaviors in adolescence. CONCLUSIONS: A package of
      interventions with teachers, parents, and children provided throughout the
      elementary grades can have enduring effects in reducing violent behavior, heavy
      drinking, and sexual intercourse by age 18 years among multiethnic urban
      children. Results are consistent with the theoretical model guiding the
      intervention and support efforts to reduce health-risk behaviors through
      universal interventions in selected communities or schools serving high-crime
      neighborhoods.

PMID- 10086399
TI  - A comparison study of an elementary school-based health center: effects on health
      care access and use.
AB  - OBJECTIVE: To assess the effects of an elementary school-based health center
      (SBHC) on access to and the use of physical and mental health services by
      children aged 4 to 13 years. STUDY DESIGN: A retrospective cohort analysis of
      parent surveys from a comparable intervention (SBHC) and a comparison of urban
      elementary schools. INTERVENTION: Elementary SBHC services, including preventive
      physical health care; the care of minor short-term illnesses, injuries, and
      stable ongoing medical conditions, dental screenings; and mental health
      counseling. PARTICIPANTS: All parents of students at both schools were asked to
      complete a survey. Return rates on the survey were 78.3% (570/728) and 77.0%
      (440/571) at the intervention and comparison schools, respectively. MAIN OUTCOME
      MEASURES: The use of health services, access to health services, and health
      service satisfaction. RESULTS: Compared with respondents at comparison schools,
      respondents whose children had access to an SBHC had less difficulty (P = .01)
      receiving physical health care for their children, ie, treatment of illnesses and
      injuries, immunizations, and physical examinations (odds ratio, 0.66; 95%
      confidence interval, 0.48-0.91). Access to an SBHC was independently and
      significantly related to less emergency department use (odds ratio, 0.63; 95%
      confidence interval, 0.40-0.99; P<.05), a greater likelihood of having had a
      physician's visit since the school year began (odds ratio, 1.92; 95% confidence
      interval, 1.39-2.65; P<.01), and a greater likelihood of having had an annual
      dental examination (odds ratio, 1.36; 95% confidence interval, 1.01-1.83; P<.05).
      Measured by a 12-item scale, respondents who reported the SBHC as their most-used
      health service were significantly more satisfied with their service than
      respondents who mostly used community clinics (z=-5.21; P<.01) or hospital
      clinics (z=-4.03; P<.01). CONCLUSIONS: Independent of insurance status and other
      confounding variables, underserved minority children with SBHC access have better
      health care access and use than children without SBHC access, signifying that
      SBHCs can be an effective component of health delivery systems for these
      children.

PMID- 10086400
TI  - Psychiatric features of children and adolescents with pseudoseizures.
AB  - BACKGROUND: Pseudoseizures may occur as a somatoform disorder in children and
      adolescents as well as adults. However, few data are available about psychiatric
      features or outcome in pediatric patients. PATIENTS AND METHODS: We studied 34
      patients (25 girls [74%]) who were evaluated by a child psychiatrist at our
      institution immediately after diagnosis of pseudoseizures by ictal video
      electroencephalogram (EEG) at ages 9 to 18 years (mean age, 14 years). Each
      patient had at least 1 pseudoseizure recorded by video EEG that was judged by the
      patient and family as typical, characterized by unresponsiveness plus limb
      twitching or limpness and other features, with EEG showing persistence of normal
      cortical background rhythms. RESULTS: In addition to conversion disorder, 11
      patients (32%) had mood disorders including major depression, bipolar disorder,
      or dysthymic disorder, usually with severe psychosocial stressors. Eight children
      (24%) had separation anxiety and school refusal with moderate psychosocial
      stressors. Two patients (6%) had brief reactive psychosis or schizophreniform
      disorder. A few (1-3) patients each had panic disorder, overanxious disorder,
      adjustment disorder, oppositional/defiant disorder, or impulse control disorder.
      Four patients (12%) also had personality disorders. Eleven patients (32%) had a
      history of sexual abuse. This was especially frequent in the subgroup with mood
      disorders (7 [64%] of 11 patients). Fifteen patients (44%) had severe family
      stressors including recent parental divorce, parental discord, or death of a
      close family member. Two patients (6%) had a history of physical abuse. Freedom
      from pseudoseizures for the preceding 9 to 55 months (mean, 30 months) was
      achieved for 15 (72%) of the 21 patients who could be reached for telephone
      follow-up. For 8 (53%) of these 15 patients, the last pseudoseizure was within 1
      month of diagnosis by video EEG. CONCLUSIONS: Major mood disorders and severe
      environmental stress, especially sexual abuse, are common among children and
      adolescents with pseudoseizures and should be considered in every case. A
      subgroup of children with separation anxiety and school refusal had less severe
      psychiatric problems and moderate psychosocial stressors. Clear diagnosis by
      video EEG, together with prompt psychiatric evaluation and treatment, may result
      in freedom from pseudoseizures for most children and adolescents.

PMID- 10086401
TI  - Sleep fragmentation in children with atopic dermatitis.
AB  - OBJECTIVE: To characterize the sleep pattern of children with atopic dermatitis
      in clinical remission. METHODS: Fourteen children with atopic dermatitis, with a
      mean+/-SD age of 6+/-2 years, were recruited consecutively from a pediatric
      dermatology clinic. No participant had any other medical or psychiatric illness.
      The control group (n = 9, mean age 7+/-1.8 years) was composed of children with
      mild "benign" snoring and no evidence of respiratory disturbance during sleep.
      All participating children were evaluated by formal all-night polysomnography,
      scratch electrodes, and self-reported questionnaires filled in by their parents.
      RESULTS: The patients were studied when their skin condition was in remission.
      Sleep latency, total sleep time, and sleep efficiency were similar to the control
      group. The atopic dermatitis group had an average of 24.1+/-8.1 events per hour
      of arousals and awakenings, compared with 15.4+/-6.2 events per hour in the
      control group (P<.001). Direct observation, video monitoring, and scratch
      electrodes provided evidence of between 1 to 19 bouts of scratching per night,
      accounting for only 15% of the arousals and awakenings. The rest of the arousals
      and awakenings were not associated with any specific, identifiable
      polysomnographic event, such as apnea or jerks. CONCLUSION: Children with atopic
      dermatitis in clinical remission have sleep disturbances that are not related to
      scratching per se.

PMID- 10086402
TI  - Use of the Pediatric Symptom Checklist to screen for psychosocial problems in
      pediatric primary care: a national feasibility study.
AB  - BACKGROUND: Routine use of a brief psychosocial screening instrument has been
      proposed as a means of improving recognition, management, and referral of
      children's psychosocial morbidity in primary care. OBJECTIVE: To assess the
      feasibility of routine psychosocial screening using the Pediatric Symptom
      Checklist (PSC) in pediatrics by using a brief version of the checklist in a
      large sample representative of the full range of pediatric practice settings in
      the United States and Canada. We evaluated large-scale screening and the
      performance of the PSC in detecting psychosocial problems by (1) determining
      whether the prevalence of psychosocial dysfunction identified by the PSC was
      consistent with findings in previous, smaller samples; (2) assessing whether the
      prevalence of positive PSC screening scores varied by population subgroups; and
      (3) determining whether the PSC was completed by a significant proportion of
      parents from all subgroups and settings. PATIENTS AND METHODS: Twenty-one
      thousand sixty-five children between the ages of 4 and 15 years were seen in 2
      large primary care networks: the Ambulatory Sentinel Practice Network and the
      Pediatric Research in Office Settings network, involving 395 pediatric and family
      practice clinicians in 44 states, Puerto Rico, and 4 Canadian provinces. Parents
      were asked to complete a brief questionnaire that included demographic
      information, history of mental health services, the 35-item PSC, and the number
      of pediatric visits within the past 6 months. RESULTS: The overall prevalence
      rates of psychosocial dysfunction as measured by the PSC in school-aged and
      preschool-aged pediatric outpatients (13% and 10%, respectively) were nearly
      identical to the rates that had been reported in several smaller samples (12%-14%
      among school-aged children and 7%-14% among preschoolers). Consistent with
      previous findings, children from low-income families were twice as likely to be
      scored as dysfunctional on the PSC than were children from higher-income
      families. Similarly, children from single-parent as opposed to those from 2
      parent families and children with a past history of mental health services showed
      an elevated risk of psychosocial impairment. The current study was the first to
      demonstrate a 50% increase in risk of impairment for male children. The overall
      rate of completed forms was 97%, well within an acceptable range, and at least
      94% of the parents in each sociodemographic subgroup completed the PSC form.
      CONCLUSIONS: Use of the PSC offers an approach to the recognition of psychosocial
      dysfunction that is sufficiently consistent across groups and locales to become
      part of comprehensive pediatric care in virtually all outpatient settings. In
      addition to its clinical utility, the consistency and widespread acceptability of
      the PSC make it well suited for the next generation of pediatric mental health
      services research, which can address whether earlier recognition of and
      intervention for psychosocial problems in pediatrics will lead to cost-effective
      outcomes.

PMID- 10086403
TI  - Immature neutrophils in the blood smears of young febrile children.
AB  - OBJECTIVE: To determine whether the immature neutrophil (band) count in the
      peripheral blood smear helps to distinguish young febrile children with bacterial
      or respiratory viral infections. DESIGN AND SETTING: A prospective cohort study
      in 3 pediatric emergency departments. PATIENTS: A convenience sample of 100
      febrile children aged 2 years or younger with either laboratory-documented
      bacterial infections (n = 31; 24 with urinary tract infections, 7 with
      bacteremia) or laboratory-documented respiratory viral infections (n = 69). Each
      patient received a clinical appearance score using the Yale Observation Scale
      prior to laboratory evaluation. A complete blood cell count was obtained from all
      patients and manual differential count of the peripheral blood smear was
      performed by 1 senior technician masked to clinical information. MAIN OUTCOME
      MEASURE: Band counts, represented as a percentage of white blood cells in the
      peripheral blood smear, the absolute band count, and band-neutrophil ratio.
      Logistic regression analysis was performed to determine whether the band count
      helps to distinguish bacterial infections from viral infections after adjusting
      for age, temperature, Yale Observation Scale score, and absolute neutrophil
      count. RESULTS: Patients with bacterial infections had a higher mean absolute
      neutrophil count (11.3 vs 5.9 x 10(9)/L; P<.01) than patients with respiratory
      viral infections. There was no difference, however, in percentage band count
      (13.5% vs 13.3%; P = .90), absolute band count (2.2 vs 1.9 X 10(9)/L; P= .31), or
      band-neutrophil ratio (0.24 vs 0.33; P = .08, bacterial vs viral, respectively);
      the band count did not help to distinguish bacterial and viral infections after
      adjusting for age, temperature, Yale Observation Scale score, and absolute
      neutrophil count in the regression analysis. CONCLUSION: The band count in the
      peripheral blood smear does not routinely help to distinguish bacterial
      infections from respiratory viral infections in young febrile children.

PMID- 10086404
TI  - Supraventricular tachycardia in infancy: evaluation, management, and follow-up.
AB  - BACKGROUND: Supraventricular tachycardia (SVT) occurs frequently in infancy.
      However, some infants have no recurrences after the initial presentation of SVT,
      and approximately 30% of infants lose SVT inducibility by 1 year of age.
      OBJECTIVE: To determine whether features at presentation, tachycardia
      characteristics, or data from an esophageal electrophysiology (EP) study could
      predict which infants will not require antiarrhythmic medication and which
      infants will not have inducible SVT at 1 year. DESIGN: Clinical and tachycardia
      characteristics at presentation of SVT and data obtained from an esophageal EP
      study were evaluated prospectively. Patients were followed up for 1 year, and an
      esophageal EP study was performed to evaluate for continued SVT inducibility.
      SETTING: Primary Children's Medical Center is a tertiary care hospital affiliated
      with the University of Utah that provides primary care to local patients and is a
      referral center for a 4-state region. PATIENTS: All infants aged 3 months or
      younger who presented with SVT between August 1995 and October 1997 were
      evaluated. INTERVENTIONS: An esophageal EP study was performed at diagnosis and
      at 1 year. RESULTS: The SVT was controlled in all 33 infants. At the initial
      esophageal EP study, the mechanism of SVT was atrioventricular node reentry in 5
      patients (15%) and orthodromic reciprocating tachycardia via an accessory
      atrioventricular connection in 28 patients (85%). One infant was lost to follow
      up, 5 never required medication, 11 had SVT controlled with propranolol
      hydrochloride, 10 had SVT controlled with amiodarone, and 6 required more than 1
      medication. Of the 21 patients who have reached 1 year of age, 16 (76%) were not
      taking any medication and were free of SVT at the time of follow-up. All 16
      patients without clinical SVT have undergone a follow-up esophageal EP study, and
      11 of 16 had inducible SVT on esophageal EP study. Thus, of the 21 one-year-old
      patients, 5 (24%) no longer had clinical or inducible SVT. CONCLUSIONS: Control
      of SVT was possible in all patients. Clinical episodes of SVT were uncommon after
      discharge, yet most still had inducible SVT at 1 year of age. No data at
      presentation or initial esophageal EP study were predictive of the clinical
      course or of continued SVT.

PMID- 10086405
TI  - Provider-reported illness and absence due to illness among children attending
      child-care homes and centers in San Diego, Calif.
AB  - PURPOSE: To compare the incidence of provider-reported illness and absence due to
      illness among children attending small child-care homes, large child-care homes,
      and child care centers in a large metropolitan area. METHODS: From July 6, 1992,
      through January 28, 1994, we collected information from child-care providers on
      illness and absence due to illness at 64 small and 58 large child-care homes and
      41 child-care centers. This included 113 446 child-weeks of information on 5360
      children. RESULTS: Providers reported 14 474 illness episodes (6.6 episodes per
      child-year) and 8593 days of absence due to illness (3.9 days per child-year).
      The incidence of illness episodes was greatest in children who were younger than
      1 year, white, or enrolled in small child-care homes. The incidence of absence
      due to illness was greatest in children who were 1 year of age, Hispanic, or
      enrolled in child-care centers. Respiratory symptoms were most commonly
      associated with illness episodes and absence due to illness. CONCLUSIONS:
      Children in child-care homes had a greater incidence of provider-reported illness
      than did those in centers. This risk varied by the type of facility and was
      greatest in small child-care homes. The increased risk for absence due to illness
      among children in child-care centers reflects exclusion and attendance patterns.
      It may be possible to reduce the incidence of absence due to illness and
      subsequent economic impact of child-care-associated illness by educating
      providers on exclusion guidelines.

PMID- 10086406
TI  - Bridging the emergency medical services for children information gap.
AB  - OBJECTIVE: To determine the epidemiological features of pediatric usage of
      prehospital emergency medical services (EMS) in a defined urban population.
      METHODS: Residents of Kansas City, Mo, younger than 15 years who used EMS during
      the calendar years 1993-1995 were included. In this geographic area there is a
      single provider of prehospital care; all numerator data were taken from this
      single source. Denominator data were provided by 1995 intercensal estimates based
      on the 1990 US Census. Rates were calculated as an annual average and reported as
      the number of children transported per 1 000 persons per year. RESULTS: There
      were a total of 7296 pediatric EMS transports during the study period, for an
      annual rate of 21.9. Infants younger than 1 year had the highest rate (47.4),
      followed by those aged 1 to 4 years (26.2), 10 to 14 years (17.5), and 5 to 9
      years (17.3). Medicaid was the insurer for half and 27% were uninsured. One
      quarter of the patients used EMS more than once. Children living in ZIP codes in
      the lowest median income tertile were 5.8 times more likely to use EMS than those
      in the upper income tertile (95% confidence interval, 5.4-6.3). One third of all
      transports occurred between the hours of 4 and 8 PM. CONCLUSIONS: Children using
      the Kansas City EMS were more likely to be infants, insured by Medicaid or
      uninsured, and live in low-income ZIP codes. Further study is needed to determine
      if this increased usage is due to greater incidence and severity of illness and
      injury, lack of transportation, lack of education, or other factors.

PMID- 10086407
TI  - The relationship between early age of onset of initial substance use and engaging
      in multiple health risk behaviors among young adolescents.
AB  - BACKGROUND: Previous research based on problem-behavior theory has found that
      early age of onset of substance use is associated with engaging in multiple
      health risk behaviors among high school students. It is unknown whether these
      relationships begin during early adolescence. OBJECTIVE: To examine the
      relationships between early age of onset of cigarette, alcohol, marijuana, and
      cocaine use and engaging in multiple risk behaviors among middle school students.
      METHODS: A modified version of the Centers for Disease Control and Prevention
      Youth Risk Behavior Survey was administered to 2227 sixth through eighth grade
      students attending 53 randomly selected middle schools in North Carolina. A
      Health Risk Behavior Scale was constructed from 16 behaviors, including
      indicators of violence and weapon carrying; current substance use; nonuse of
      helmets when biking, in-line skating or skateboarding; not wearing a seat belt;
      riding with a driver who had been drinking; and suicide plans. Among this sample
      of middle school students, the scale had a mean (SD) of 4.1 (2.7) (range=O-15),
      and had a high internal reliability coefficient (alpha(=0.74). The independent
      variables included first time use of cigarettes, alcohol, marijuana, and cocaine
      at age 11 years or earlier; actual age of onset of each substance; race and
      ethnicity; family composition; sex; school grade; academic ranking; and older age
      for school grade. These data were analyzed with analysis of variance, Spearman r,
      and multiple linear regression. RESULTS: All the independent variables were found
      to be associated (P<.005) with the Health Risk Behavior Scale during the
      bivariate analyses. When each of these significant variables were entered into a
      multiple regression model, having smoked at age 11 years or younger accounted for
      21.9% of the variation in the Health Risk Behavior Scale. Male sex, early
      marijuana or cocaine use, older age, lower academic rank, white race, and living
      in a 1-parent family explained an additional 19.1% of variation in the model
      (adjusted R2=0.41, P<.001). When the actual ages of onset of the use of
      substances were analyzed, in order of magnitude; age of onset of smoking; male
      sex; age of onset of alcohol and marijuana use; age; lower academic ranking; age
      of onset of cocaine use; white race; and lower academic rating accounted for
      52.8% (P<.001) of the variation in the Health Risk Behavior Scale. CONCLUSION:
      Even when considering sociodemographic factors, early age of onset of cigarette
      use was the strongest correlate of the number of health risk behaviors in which
      these young adolescents had engaged. Early onset of use of other substances was
      also associated with a clustering of health risk behaviors among this sample of
      middle school students. The findings suggest that screening for early
      experimentation with tobacco and other substance use will help identify young
      adolescents at increased risk for engaging in multiple health risk behaviors.

PMID- 10086408
TI  - After-hours telephone triage and advice in private and nonprivate pediatric
      populations.
AB  - OBJECTIVES: To compare the content of after-hours medical triage and advice calls
      regarding private practice patients vs nonprivate practice patients and to assess
      caregiver compliance with advice resulting from these calls. DESIGN: Survey of
      after-hours medical triage and advice calls during a 2-week period (September 1
      through 15, 1996). SETTING: Three private practices (serving approximately 24 000
      patients) and 1 urban hospital-based, non-private practice (serving approximately
      12 000 patients). SUBJECTS: After-hours medical triage and advice calls from
      caregivers of patients receiving their primary care in these settings. MAIN
      OUTCOME MEASURE: Compliance with recommended emergency department (ED) or office
      visit referrals. RESULTS: A total of 286 calls regarding private practice
      patients and 377 calls regarding nonprivate practice patients were received
      (P<.001). Eighty-one calls were referred by the nurse directly to the physician.
      Fifty-nine private practice patients and 59 nonprivate practice patients were
      referred to the ED. Caregivers of 94 private practice patients and 132 nonprivate
      practice patients were given home treatment advice. Appointments to be seen at
      their primary care source were given for 78 private practice patients and 160
      nonprivate practice patients. Non-private practice patients were more likely to
      be referred for office care (P=.005); private practice patients were more likely
      to be referred to the ED (P=.01). Compliance with ED referrals was 42% for
      patients of nonprivate practice and 46% for private practice; for office visit
      referrals, compliance was 64% for nonprivate practice and 69% private practice
      patients (P=.71 for compliance with ED referrals and P=.40 for compliance with
      office referrals). CONCLUSIONS: Compliance with recommended physician encounters
      was not significantly different (and lower than expected) in both groups of
      patients. Private practice patients are more likely to be referred to the ED.
      Calls for nonprivate practice patients are more frequent and these patients are
      more likely to be referred to their primary care source. This difference may be
      due to caregivers of patients from nonprivate practices seeking advice for less
      serious conditions. Physicians should address telephone medicine with caregivers
      proactively during health maintenance visits.

PMID- 10086409
TI  - Trends in clinical education of medical students: implications for pediatrics.
AB  - OBJECTIVES: To describe current educational imperatives and trends for curricular
      changes in the clinical education of medical students and to delineate the nature
      and extent of participation in these curricular trends by departments of
      pediatrics. METHODS: Site visits to 26 representative US medical schools and a
      review of detailed information from 12 additional schools. Evaluation of the core
      curriculum was developed by the Council on Medical Student Education in
      Pediatrics within the context of the major curricular trends observed. RESULTS:
      The major observed curricular trends emphasized community-based ambulatory
      experiences, continuity of care, integration, and population-based experiences.
      Supporting educational principles included student-directed learning and
      performance-based assessments. The 3 major curricular changes were early clinical
      experiences (longitudinal preceptorships), community-oriented/ population-based
      experiences, and multispecialty clerkships. The focus of the Council on Medical
      Student Education in Pediatrics objectives was the year 3 clerkship, and
      substantive participation by pediatric faculty in the overall curriculum was
      primarily related to the pediatric clerkship. CONCLUSIONS: Revising the clerkship
      based Council on Medical Student Education in Pediatrics guidelines according to
      the new educational trends will extend clinical curricular opportunities for
      pediatrics beyond the traditional boundaries of the clerkship. The discipline of
      pediatrics will, as a consequence, be able to achieve enhanced partnership in the
      planning, conduct, and evaluation of a clinical curriculum for medical students
      that is relevant to child health issues and that extends across all 4 years.

PMID- 10086410
TI  - Radiological case of the month. Superior mesenteric artery syndrome.

PMID- 10086411
TI  - Picture of the month. Tinea nigra.

PMID- 10086412
TI  - Pathological case of the month. Epidermal nevi.

PMID- 10086413
TI  - Sleep terrors in a 5-year-old girl.

PMID- 10086414
TI  - Foreign body in the esophagus as a result of reusing a disposable nipple.

PMID- 10086415
TI  - Immunization refusal and physician responsibility.

PMID- 10086416
TI  - Substance abuse prevention and the media.

PMID- 10086417
TI  - Internet resources in otolaryngology-head and neck surgery.

PMID- 10086418
TI  - Ovarian cancer investigators aim at cell signaling pathways.

PMID- 10086419
TI  - Several groups attempting regulation of Internet Rx.

PMID- 10086420
TI  - "Epidemic!" exhibits infectious disease world.

PMID- 10086421
TI  - Confidential Spanish registry of HIV-infected individuals.

PMID- 10086422
TI  - From the Centers for Disease Control and Prevention. Adverse events associated
      with ingestion of gamma-butyrolactone--Minnesota, New Mexico, and Texas, 1998
      1999.

PMID- 10086423
TI  - From the Centers for Disease Control and Prevention. Farm worker illness
      following exposure to carbofuran and other pesticides--Fresno County, California,
      1998.

PMID- 10086424
TI  - From the Centers for Disease Control and Prevention. Recall of Tripedia vaccine.

PMID- 10086425
TI  - Putting babies "back to sleep".

PMID- 10086426
TI  - Defining and improving health care quality.

PMID- 10086427
TI  - Defining and improving health care quality.

PMID- 10086428
TI  - Clinical crossroads: a 29-year-old man with multiple sclerosis.

PMID- 10086429
TI  - Clinical crossroads: a 29-year-old man with multiple sclerosis.

PMID- 10086430
TI  - Ergotism related to concurrent administration of ergotamine tartrate and
      indinavir.

PMID- 10086431
TI  - Powder-free protein-poor natural rubber latex gloves and latex sensitization.

PMID- 10086432
TI  - Internet access and use among disadvantaged inner-city patients.

PMID- 10086433
TI  - Behavioral and pharmacological therapies for late-life insomnia: a randomized
      controlled trial.
AB  - CONTEXT: Insomnia is a prevalent health complaint in older adults. Behavioral and
      pharmacological treatments have their benefits and limitations, but no placebo
      controlled study has compared their separate and combined effects for late-life
      insomnia. OBJECTIVE: To evaluate the clinical efficacy of behavioral and
      pharmacological therapies, singly and combined, for late-life insomnia. DESIGN
      AND SETTING: Randomized, placebo-controlled clinical trial, at a single academic
      medical center. Outpatient treatment lasted 8 weeks with follow-ups conducted at
      3, 12, and 24 months. SUBJECTS: Seventy-eight adults (50 women, 28 men; mean age,
      65 years) with chronic and primary insomnia. INTERVENTIONS: Cognitive-behavior
      therapy (stimulus control, sleep restriction, sleep hygiene, and cognitive
      therapy) (n = 18), pharmacotherapy (temazepam) (n = 20), or both (n = 20)
      compared with placebo (n = 20). MAIN OUTCOME MEASURES: Time awake after sleep
      onset and sleep efficiency as measured by sleep diaries and polysomnography;
      clinical ratings from subjects, significant others, and clinicians. RESULTS: The
      3 active treatments were more effective than placebo at posttreatment assessment;
      there was a trend for the combined approach to improve sleep more than either of
      its 2 single components (shorter time awake after sleep onset by sleep diary and
      polysomnography). For example, the percentage reductions of time awake after
      sleep onset was highest for the combined condition (63.5%), followed by cognitive
      behavior therapy (55%), pharmacotherapy (46.5%), and placebo (16.9%). Subjects
      treated with behavior therapy sustained their clinical gains at follow-up,
      whereas those treated with drug therapy alone did not. Long-term outcome of the
      combined intervention was more variable. Behavioral treatment, singly or
      combined, was rated by subjects, significant others, and clinicians as more
      effective than drug therapy alone. Subjects were also more satisfied with the
      behavioral approach. CONCLUSIONS: Behavioral and pharmacological approaches are
      effective for the short-term management of insomnia in late life; sleep
      improvements are better sustained over time with behavioral treatment.

PMID- 10086434
TI  - Moderate- vs high-dose methadone in the treatment of opioid dependence: a
      randomized trial.
AB  - CONTEXT: Methadone hydrochloride treatment is the most common pharmacological
      intervention for opioid dependence, and recent interest has focused on expanding
      methadone treatment availability beyond traditional specially licensed clinics.
      However, despite recommendations regarding effective dosing of methadone,
      controlled clinical trials of higher-dose methadone have not been conducted.
      OBJECTIVE: To compare the relative clinical efficacy of moderate- vs high-dose
      methadone in the treatment of opioid dependence. DESIGN: A 40-week randomized,
      double-blind clinical trial starting in June 1992 and ending in October 1995.
      SETTING: Outpatient substance abuse treatment research clinic at the Johns
      Hopkins University Bayview Campus, Baltimore, Md. PARTICIPANTS: One hundred
      ninety-two eligible clinic patients. INTERVENTION: Daily oral methadone
      hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95),
      with concurrent substance abuse counseling. MAIN OUTCOME MEASURES: Opioid
      positive urinalysis results and retention in treatment. RESULTS: By intent-to
      treat analysis through week 30 patients in the high-dose group had significantly
      lower rates of opioid-positive urine samples compared with patients in the
      moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9%
      [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal
      from methadone. Through day 210 no significant difference was evident between
      dose groups in treatment retention (high-dose group mean retention, 159 days;
      moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in
      the high-dose group and 11 (20%) of 54 patients in the moderate-dose group
      completed detoxification. CONCLUSIONS: Both moderate- and high-dose methadone
      treatment resulted in decreased illicit opioid use during methadone maintenance
      and detoxification. The high-dose group had significantly greater decreases in
      illicit opioid use.

PMID- 10086435
TI  - Ethnic variation in cardiovascular disease risk factors among children and young
      adults: findings from the Third National Health and Nutrition Examination Survey,
      1988-1994.
AB  - CONTEXT: Knowledge about ethnic differences in cardiovascular disease (CVD) risk
      factors among children and young adults from national samples is limited.
      OBJECTIVE: To evaluate ethnic differences in CVD risk factors, the age at which
      differences were first apparent, and whether differences remained after
      accounting for socioeconomic status (SES). DESIGN: Third National Health and
      Nutrition Examination Survey, 1988-1994. SETTING: Eighty-nine mobile examination
      centers. PARTICIPANTS: A total of 2769 black, 2854 Mexican American, and 2063
      white (non-Hispanic) children and young adults aged 6 to 24 years. MAIN OUTCOME
      MEASURES: Ethnicity and household level of education (SES) in relation to body
      mass index (BMI), percentage of energy from dietary fat, cigarette smoking,
      systolic blood pressure, glycosylated hemoglobin (HbA1c), and non-high-density
      lipoprotein cholesterol (non-HDL-C [the difference between total cholesterol and
      HDL-C]). RESULTS: The BMI levels were significantly higher for black and Mexican
      American girls than for white girls, with ethnic differences evident by the age
      of 6 to 9 years (a difference of approximately 0.5 BMI units) and widening
      thereafter (a difference of >2 BMI units among 18- to 24-year-olds). Percentages
      of energy from dietary fat paralleled these findings and were also significantly
      higher for black than for white boys. Blood pressure levels were higher for black
      girls than for white girls in every age group, and glycosylated hemoglobin levels
      were highest for black and Mexican American girls and boys in every age group. In
      contrast, smoking prevalence was highest for white girls and boys, especially for
      those from low-SES homes (77% of young men and 61% of young women, aged 18-24
      years, from low-SES homes were current smokers). All ethnic differences remained
      significant after accounting for SES and age. CONCLUSION: These findings show
      strong ethnic differences in CVD risk factors among youths of comparable age and
      SES from a large national sample. The differences highlight the need for heart
      disease prevention programs to begin early in childhood and continue throughout
      young adulthood to reduce the risk of atherosclerosis.

PMID- 10086436
TI  - Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from
      a public health tuberculosis clinic.
AB  - CONTEXT: Isoniazid preventive therapy for latent tuberculosis (TB) infection has
      been debated because of the risk of hepatotoxicity. The frequency of
      hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new
      criteria for diagnosis and patient selection. OBJECTIVE: To determine the rate of
      isoniazid hepatotoxicity in patients managed according to current guidelines and
      practice standards. DESIGN: Prospective cohort study. SETTING: A public health
      clinic operated by the TB control program of a city-county public health agency.
      PATIENTS: A total of 11141 consecutive patients who started a regimen of
      isoniazid preventive therapy for latent TB infection from January 1989 through
      December 1995. MAIN OUTCOME MEASURES: The rate of developing symptoms and signs
      of hepatotoxicity among all persons starting isoniazid preventive therapy, among
      all those completing therapy, and by age, sex, and race. RESULTS: Eleven patients
      (0.10% of those starting, and 0.15% of those completing treatment) had
      hepatotoxic reactions to isoniazid during preventive treatment. The rate of
      hepatotoxicity in persons receiving preventive therapy increased with increasing
      age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased
      rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45;
      chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08;
      P=.08). CONCLUSIONS: The rate of isoniazid hepatotoxicity during clinically
      monitored preventive therapy was lower than has been reported previously.
      Clinicians should have greater confidence in the safety of isoniazid preventive
      therapy.

PMID- 10086437
TI  - Perceived risks of heart disease and cancer among cigarette smokers.
AB  - CONTEXT: Cigarette smoking causes more preventable deaths from cardiovascular
      disease and cancer than any other modifiable risk factor, but smokers may
      discount the increased personal risk they face from continued smoking. OBJECTIVE:
      To assess smokers' perceptions of their risks of heart disease and cancer. DESIGN
      AND SETTING: Telephone and self-administered survey in 1995 of a probability
      sample of US households with telephones. PARTICIPANTS: A total of 3031 adults
      aged 25 to 74 years, including 737 current smokers (24.3%). MAIN OUTCOME
      MEASURES: Respondents with no history of myocardial infarction (MI) (96.2 %) or
      cancer (92.9%) assessed their risk of these conditions relative to other people
      of the same age and sex. Among current smokers, perceived risks were analyzed by
      demographic and clinical factors using logistic regression. RESULTS: Only 29% and
      40% of current smokers believed they have a higher-than-average risk of MI or
      cancer, respectively, and only 39% and 49% of heavy smokers (> or =40 cigarettes
      per day) acknowledged these risks. Even among smokers with hypertension, angina,
      or a family history of MI, 48%, 49%, and 39%, respectively, perceived their risk
      of MI as higher than average. In multivariate analyses, older (> or =65 years),
      less educated (< high school graduate), and light smokers (1-19 cigarettes per
      day) were less likely than younger, more educated, and heavy smokers to perceive
      an increased personal risk of MI or cancer. CONCLUSIONS: Most smokers do not view
      themselves at increased risk of heart disease or cancer. As part of multifaceted
      approaches to smoking cessation, physicians and public health professionals
      should identify and educate smokers who are not aware of smoking-related health
      risks.

PMID- 10086438
TI  - The rational clinical examination. Is this patient hypovolemic?
AB  - OBJECTIVE: To review, systematically, the physical diagnosis of hypovolemia in
      adults. METHODS: We searched MEDLINE (January 1966-November 1997), personal
      files, and bibliographies of textbooks on physical diagnosis and identified 10
      studies investigating postural vital signs or the capillary refill time of
      healthy volunteers, some of whom underwent phlebotomy of up to 1150 mL of blood,
      and 4 studies of patients presenting to emergency departments with suspected
      hypovolemia, usually due to vomiting, diarrhea, or decreased oral intake.
      RESULTS: When clinicians evaluate adults with suspected blood loss, the most
      helpful physical findings are either severe postural dizziness (preventing
      measurement of upright vital signs) or a postural pulse increment of 30 beats/min
      or more. The presence of either finding has a sensitivity for moderate blood loss
      of only 22% (95% confidence interval [CI], 6%-48%) but a much greater sensitivity
      for large blood loss of 97% (95% CI, 91%-100%); the corresponding specificity is
      98% (95% CI, 97%-99%). Supine hypotension and tachycardia are frequently absent,
      even after up to 1150 mL of blood loss (sensitivity, 33%; 95% CI, 21%-47%, for
      supine hypotension). The finding of mild postural dizziness has no proven value.
      In patients with vomiting, diarrhea, or decreased oral intake, the presence of a
      dry axilla supports the diagnosis of hypovolemia (positive likelihood ratio, 2.8;
      95% CI, 1.4-5.4), and moist mucous membranes and a tongue without furrows argue
      against it (negative likelihood ratio, 0.3; 95% CI, 0.1-0.6 for both findings).
      In adults, the capillary refill time and poor skin turgor have no proven
      diagnostic value. CONCLUSIONS: A large postural pulse change (> or =30 beats/min)
      or severe postural dizziness is required to clinically diagnose hypovolemia due
      to blood loss, although these findings are often absent after moderate amounts of
      blood loss. In patients with vomiting, diarrhea, or decreased oral intake, few
      findings have proven utility, and clinicians should measure serum electrolytes,
      serum blood urea nitrogen, and creatinine levels when diagnostic certainty is
      required.

PMID- 10086439
TI  - From disease prevention to health promotion.

PMID- 10086440
TI  - Treating insomnia in older adults: taking a long-term view.

PMID- 10086441
TI  - Perils, pitfalls, and possibilities in talking about medical risk.
AB  - Virtually every course of medical action is associated with some adverse risk to
      the patient. Discussing these risks with patients is a fundamental duty of
      physicians both to fulfill a role as trusted adviser and to promote the ethical
      principle of autonomy (particularly as embodied in the doctrine of informed
      consent). Discussing medical risk is a difficult task to accomplish
      appropriately. Challenges stem from gaps in the physician's knowledge about
      pertinent risks, uncertainty about how much and what kind of information to
      communicate, and difficulties in communicating risk information in a format that
      is clearly understood by most patients. For example, a discussion of the risk of
      undergoing a procedure should be accompanied by a discussion of the risk of not
      undergoing a procedure. This article describes basic characteristics of risk
      information, outlines major challenges in communicating risk information, and
      suggests several ways to communicate risk information to patients in an
      understandable format. Ultimately, a combination of formats (eg, qualitative,
      quantitative, and graphic) may best accommodate the widely varying needs,
      preferences, and abilities of patients. Such communication will help the
      physician accomplish the fundamental duty of teaching the patient the information
      necessary to make an informed and appropriate decision.

PMID- 10086442
TI  - JAMA patient page: insomnia.

PMID- 10086443
TI  - Amiodarone-induced pigmentation resolves after treatment with the Q-switched ruby
      laser.

PMID- 10086444
TI  - Dermatologists should guard their patients' purse, not pick their pockets!

PMID- 10086445
TI  - Study of the Food and Drug Administration files on Propecia: dosages, side
      effects, and recommendations.

PMID- 10086446
TI  - Genetic and environmental influences in the development of multiple primary
      melanoma.
AB  - OBJECTIVES: To identify risk factors and the prognosis associated with the
      development of multiple primary melanoma (MPM). DESIGN: Case-comparison studies
      of subjects with MPM and single primary melanoma. Sequencing of CDKN2A in
      germline DNA. SETTING: Population-based study of patients with invasive melanoma
      in Scotland between 1979 and 1996. PATIENTS: For mortality studies, 108 patients
      with MPM and 216 single melanoma controls matched for age, sex, site, and tumor
      thickness. For risk factor studies, 48 patients with MPM and 48 single melanoma
      controls matched as above. For CDKN2A analysis, a sample of 23 subjects with MPM.
      RESULTS: The development of MPM was found not to be an independent prognostic
      factor. The risk of MPM was greatest in those with a family history of melanoma,
      with large numbers of benign nevi, and the presence of clinically or
      histologically atypical nevi. Germline mutations of CDKN2A were present in 6 of
      23 patients with MPM and in 5 cases consisted of the base pair substitution
      Met53Ile. CONCLUSIONS: The importance of MPM should be addressed in melanoma
      follow-up protocols. Those patients at greatest risk can be identified by a
      family history of melanoma and their mole pattern. Germline mutations in CDKN2A
      occur in both familial and sporadic MPM and further studies are required to
      determine the value of analysis of this gene in melanoma surveillance. Patients
      should be informed that the development of MPM does not adversely affect their
      prognosis.

PMID- 10086447
TI  - Melanoma and tumor thickness: challenges of early diagnosis.
AB  - OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of
      melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN:
      Prospective study of the correlation between delays to diagnosis, assessed using
      a questionnaire, and the Breslow thickness as a prognosis marker. SETTING:
      Dermatology departments in France. PATIENTS: Five hundred ninety consecutive
      patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN
      OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time
      the patients realized that they had a lesion until the resection of the melanoma,
      and results of the correlation between each time interval and tumor thickness
      (Breslow). RESULTS: There is a positive but weak correlation between tumor
      thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009).
      However, this delay tends to be short for the thickest tumors. There is a
      negative correlation between tumor thickness and the delay to seek medical
      attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No
      correlation is found between melanoma thickness and physicians' delays.
      CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing
      tumors rather than by delays. In well-informed populations, campaigns for early
      diagnosis of melanoma may thus no longer have a major impact on prognosis, unless
      they are focused on subgroups less accessible to information and medical care.

PMID- 10086448
TI  - Analysis of the melanoma epidemic, both apparent and real: data from the 1973
      through 1994 surveillance, epidemiology, and end results program registry.
AB  - BACKGROUND: The incidence of melanoma has been increasing faster than that of any
      other cancer in the United States. It is unclear whether the increase is related
      to increased surveillance or other changes in the disease. OBJECTIVE: To examine
      changes in melanoma rates by several measures of severity of disease and to
      review the ways in which increased surveillance may cause lead-time bias through
      early detection or length bias through detection of clinically insignificant
      lesions as a basis for interpreting these changing rates. DESIGN: Population
      based incidence rates for 1973 through 1994. SETTING: United States Surveillance,
      Epidemiology, and End Results Program tumor registries. PATIENTS: A total of
      47,638 cases of melanoma among white patients aged 20 years and older. MAIN
      OUTCOME MEASURES: Relative incidence rates for melanoma by stage, and tumor
      thickness adjusted for age and sex. RESULTS: Localized-stage melanoma increased,
      but no significant change for distant-stage melanomas was seen. Among those
      diagnosed from 1988 through 1994, there were 22%, 26%, and 31% increases for
      tumor thickness less than 1.0 mm, between 1.0 and 3.0 mm, and 3.0 mm or greater,
      respectively. The 2-year mortality rates also increased over time. CONCLUSIONS:
      While these data show large increases in early disease (localized stage, thin
      tumors), they also suggest some increase in advanced disease (thick tumors, 2
      year mortality). This indicates that the increasing incidence rates of melanoma
      are not solely caused by increased early detection and diagnosis of clinically
      insignificant melanomas, but may also represent a true increase in cancer rates.

PMID- 10086449
TI  - Spitz tumors in children: a grading system for risk stratification.
AB  - OBJECTIVE: To describe a grading system for risk stratification of atypical Spitz
      tumors in children and adolescents. In some circumstances, unequivocal
      distinction between Spitz nevus and melanoma is practically impossible. It is
      likely that these lesions for which we lack specific diagnostic criteria
      represent a broad histological continuum extending from benign to malignant
      tumors. Therefore, we propose that Spitz tumors be categorized into low-,
      intermediate-, or high-risk categories based on the accumulation of abnormal
      features. DESIGN: Retrospective study. SETTINGS: Institutional practice.
      PATIENTS: We present 30 cases of atypical Spitz tumors in patients younger than
      18 years evaluated for at least 3 years or in whom a metastatic event developed
      during this period. INTERVENTION: None. MAIN OUTCOME MEASURE: The grading system
      was formulated after data collection. RESULTS: Among the parameters studied, only
      diagnosis at age greater than 10 years, diameter of the lesion greater than 10
      mm, presence of ulceration, involvement of the subcutaneous fat (level V), and
      mitotic activity of at least 6/mm2 carried a likelihood ratio greater than 1.50
      and were therefore used for the grading system. CONCLUSION: The application of an
      objective grading system, such as the one described herein for the first time, is
      the first step in providing useful information for the management of atypical
      Spitz tumors.

PMID- 10086450
TI  - Treatment of benign and atypical nevi with the normal-mode ruby laser and the Q
      switched ruby laser: clinical improvement but failure to completely eliminate
      nevomelanocytes.
AB  - OBJECTIVE: To evaluate the effect of normal-mode and Q-switched ruby laser light
      (694 nm) on nevomelanocytes of benign, atypical, and congenital nevi. DESIGN:
      Half of the lesion of each of 31 nevi was treated with either the Q-switched ruby
      laser or the normal-mode ruby laser or both; the other half of the lesion was
      covered with aluminum foil and was not treated. SETTING: A university-affiliated,
      hospital-based laser center. PATIENTS: Sixteen patients with a total of 31
      melanocytic nevi were enrolled in the study. INTERVENTIONS: All nevi were
      evaluated by at least 2 dermatologists to assess the degree of clinical atypia.
      Photographs were taken before and immediately after treatment and at each follow
      up visit. The digital imaging system was used to evaluate the number of
      melanocytes in a measured length of basement membrane zone. MAIN OUTCOME MEASURE:
      Three individual readings (number of melanocytes per unit length) were taken on
      both the control and treated halves and then compared to quantitate treatment
      effect. All analyses used averages from 3 measurements. A Student paired t test
      was used to compare the treated and untreated sides. RESULTS: Sixteen (52%) of
      the nevi showed a clinically visible decrease in pigment on the treatment side at
      the 4-week follow-up visit. CONCLUSION: No lesions had complete histologic
      removal of all nevomelanocytes. Therefore, 1 or 2 laser treatments are not
      sufficient to cause complete removal of a lesion either clinically or
      histologically.

PMID- 10086451
TI  - Top cited authors in dermatology: a citation study from 24 journals: 1982-1996.
AB  - BACKGROUND: One measure of the impact of a medical article is how often it is
      cited in other articles. Many authors of articles published in dermatologic
      journals are seldom, if ever, cited while other authors are often cited.
      OBJECTIVE: To identify the 25 authors whose publications in the dermatology
      literature were most often cited. DESIGN: We obtained a citation database from
      the Institute for Scientific Information. From this database we separately
      quantified the total number of citations for each author and the total number of
      citations to first authors of original articles. SETTING: Dermatology journals.
      SUBJECTS: All authors of papers published in 24 dermatology journals between 1981
      and 1996. INTERVENTION: None. MAIN OUTCOME MEASURE: Number of citations. RESULTS:
      If all articles irrespective of the author's listing (eg, first or second) are
      counted, the top 25 cited authors in the dermatology literature from 1981 to 1996
      were cited between 1480 and 4706 times. If only citations and articles of which
      an author was the first listed author are counted, the top 25 authors were cited
      between 400 and 813 times. Only 4 authors were among the top 25 cited authors by
      both criteria. CONCLUSIONS: A relatively small proportion of all authors account
      for a high proportion of all citations of the dermatologic literature. The most
      frequently cited first authors of original articles were different in 84% of
      cases from the most often cited authors of all papers irrespective of the
      individuals placement in the authorship listing.

PMID- 10086452
TI  - Induction of hyperacute graft-vs-host disease after donor leukocyte infusions.
AB  - BACKGROUND: Infusions of leukocytes obtained from the original bone marrow donor
      is a new approach for treating patients who have a relapse of leukemia after
      allogeneic bone marrow transplantation. Up to 90% of patients who achieved
      remission developed graft-vs-host disease (GVHD). However, any description of the
      clinical and histologic features in these cases is lacking. OBSERVATIONS: We
      describe 2 patients in whom a severe, peculiar, hyperacute, fatal GVHD developed
      after treatment with donor leukocyte infusions and interferon alfa. The patients
      had not received any additional chemotherapy or GVHD prophylaxis. In both
      patients, the eruption started with the appearance of erythematous plaques at the
      interferon alfa injection sites, and a generalized maculopapular eruption
      subsequently developed. The clinical lesions evolved from acute to lichenoid
      within several days. The histologic examination also demonstrated unusual
      findings and showed features of both acute and chronic lichenoid GVHD.
      CONCLUSIONS: Donor leukocyte infusions without GVHD prophylaxis may provoke a
      severe fatal hyperacute GVHD. In the cases presented herein, we discuss the
      significance of the rapid clinical evolution from acute to lichenoid and the
      combination of histologic features of both acute and chronic GVHD in the biopsy
      specimens.

PMID- 10086453
TI  - Cutaneous manifestations of biological warfare and related threat agents.
AB  - The specter of biological warfare (BW) looms large in the minds of many
      Americans. The US government has required that emergency response teams in more
      than 100 American cities be trained by the year 2001 to recognize and contain a
      BW attack. The US military is requiring active duty soldiers to receive
      immunization against anthrax. Dermatologists need not feel helpless in the face
      of a potential BW attack. Many potential agents have cutaneous manifestations
      that the trained eye of a dermatologist can recognize. Through early recognition
      of a BW attack, dermatologists can aid public health authorities in diagnosing
      the cause so that preventive and containment measures can be instituted to
      mitigate morbidity and mortality. This article reviews bacterial, viral, and
      toxin threat agents and emphasizes those that would have cutaneous manifestations
      following an aerosol attack. We conclude with clues that can help one recognize a
      biological attack.

PMID- 10086454
TI  - JAMA and editorial independence.

PMID- 10086455
TI  - Multiple primary melanoma is not a distinct biological entity.

PMID- 10086456
TI  - The golden anniversary of the Spitz nevus.

PMID- 10086457
TI  - Thickness and delay in diagnosis of melanoma: how far can we go?

PMID- 10086458
TI  - Subscapular subcutaneous tumor.

PMID- 10086459
TI  - An erythematous noduloplaque on the trunk.

PMID- 10086460
TI  - Multiple nodules on the back.

PMID- 10086461
TI  - Multiple papular and nodular lesions on the extremities and trunk.

PMID- 10086462
TI  - Lymphedema-distichiasis syndrome: report of a case and review.

PMID- 10086463
TI  - UV-A1 for keloid.

PMID- 10086464
TI  - Mucosal denudation of the lips from isotretinoin therapy.

PMID- 10086465
TI  - High-dose trimethoprim-sulfamethoxazole therapy with corticosteroids in
      previously intolerant patients with AIDS-associated Pneumocystis carinii
      pneumonia.

PMID- 10086466
TI  - Ivermectin in elderly patients.

PMID- 10086467
TI  - Patient survey of trichloroacetic acid treatment of facial actinic keratoses.

PMID- 10086468
TI  - Soteria and the medical marketplace.

PMID- 10086469
TI  - Neuropsychology and the self-concept.
AB  - The biological basis of the self is discussed in relation to neuropsychological
      findings in cases with focal brain injury. This material demonstrates that the
      self is deposited at an early phase in the process of object realization and
      distributes into the private space of imagery and the external space of object
      perception. A disruption or truncation of this process results in an erosion of
      the self that is similar across the different perceptual modalities. From the
      pattern of pathological breakdown, it is concluded that the self is a
      categorical, relational entity that achieves autonomy in the context of an act of
      cognition that is fully derived, i.e., actualizes completely. The autonomy
      depends on the completeness of this derivation. The preliminary locus of the self
      in the mental state entails a holistic or multimodal phase of potential before
      perceptual individuation. The relation of the self-concept to antecedent phases
      in the microgenesis of a cognition, the relation to feeling, personal history,
      and the immediate past, points to a limbic transition in the outward development
      of the mental state.

PMID- 10086470
TI  - Soteria and other alternatives to acute psychiatric hospitalization: a personal
      and professional review.
AB  - The author reviews the clinical and special social environmental data from the
      Soteria Project and its direct successors. Two random assignment studies of the
      Soteria model and its modification for long-term system clients reveal that
      roughly 85% to 90% of acute and long-term clients deemed in need of acute
      hospitalization can be returned to the community without use of conventional
      hospital treatment. Soteria, designed as a drug-free treatment environment, was
      as successful as anti-psychotic drug treatment in reducing psychotic symptoms in
      6 weeks. In its modified form, in facilities called Crossing Place and McAuliffe
      House where so-called long-term "frequent flyers" were treated, alternative
      treated subjects were found to be as clinically improved as hospital-treated
      patients, at considerably lower cost. Taken as a body of scientific evidence, it
      is clear that alternatives to acute psychiatric hospitalization are as, or more,
      effective than traditional hospital care in short-term reduction of
      psychopathology and longer-term social adjustment. Data from the original drug
      free, home-like, nonprofessionally staffed Soteria Project and its Bern,
      Switzerland, replication indicate that persons without extensive hospitalizations
      (<30 days) are especially responsive to the positive therapeutic effects of the
      well-defined, replicable Soteria-type special social environments. Reviews of
      other studies of diversion of persons deemed in need of hospitalization to
      "alternative" programs have consistently shown equivalent or better program
      clinical results, at lower cost, from alternatives. Despite these clinical and
      cost data, alternatives to psychiatric hospitalization have not been widely
      implemented, indicative of a remarkable gap between available evidence and
      clinical practice.

PMID- 10086471
TI  - Long-term effects of childhood sexual abuse: objective and subjective
      characteristics of the abuse and psychopathology in later life.
AB  - This study investigates the association between objective and subjective
      characteristics of childhood sexual abuse and psychopathology in later life. The
      sample consists of 404 Dutch female adults who had been sexually abused in their
      childhood or adolescence. The participants were recruited by means of articles
      about childhood sexual abuse in major Dutch newspapers. The characteristics and
      severity of the sexual abuse were assessed with the Questionnaire Unwanted Sexual
      Experiences in the Past (QUSEP). General psychopathology was measured with the
      Symptom Checklist (SCL-90), the degree of dissociation was measured with the
      Dissociation Questionnaire (DIS-Q). Stepwise multiple regression analyses showed
      a moderate association between psychopathology and objective characteristics of
      the abuse, such as number of different types of abusive events and the duration
      of the abuse. However, more strongly associated with later psychopathology were
      variables reflecting coping style, such as the degree of self-blame, and
      circumstantial factors, such as the emotional atmosphere in the family of origin
      and the reactions after disclosure. Whether or not the abuse was incestuous did
      not explain additional variance in later psychopathology.

PMID- 10086472
TI  - The role of fear in delusions of the paranormal.
AB  - Based on an extended process model derived from attribution theory, we
      hypothesized that pervasive and persistent delusions of the paranormal are
      characterized by the existence of a positive (self-reinforcing), rather than a
      negative (self-correcting), feedback loop involving paranormal beliefs, fears,
      and experiences, as moderated by gender and tolerance of ambiguity. A cross
      cultural sample of "international" students who reported poltergeist-like
      experiences showing high fear of the paranormal was identified. As in earlier
      research, path analysis showed statistically significant and positive effects of
      belief on experience and/or fear on belief. However, paranormal experience now
      had a positive effect on fear as well. Thus, as predicted, increased fear removes
      the option of neutralizing ambiguous events by labeling them as "paranormal."
      Although female subjects showed significantly greater fear of the paranormal than
      male subjects, there is no evidence that the nature of the delusional process is
      gender specific.

PMID- 10086473
TI  - Diagnostic efficiency and hierarchical functioning of the DSM-IV borderline
      personality disorder criteria.
AB  - This study presents information regarding the diagnostic efficiency and
      hierarchical functioning of the newly revised DSM-IV borderline personality
      disorder (BPD) criteria. Past research using the DSM-III-R version of BPD showed
      that the individual BPD criteria differ greatly in their diagnostic utility and
      that in some clinical situations, fewer than five of eight criteria could
      efficiently make the diagnosis. Two groups of inpatients, a BPD group (N = 33)
      and a non-BPD group (N = 43), were rated on the DSM-IV BPD criteria. Acceptable
      interrater reliability (Kappa estimates) was obtained for the presence or absence
      of the nine individual BPD criteria. Diagnostic efficiency statistics,
      sensitivity, specificity, false positive and false negative rates, positive
      predictive power, negative predictive power, overall classification rate and
      Kappa with the clinical diagnosis were obtained for all nine BPD criteria. The
      diagnostic efficiency data indicated that BPD criteria 1 (abandonment) and 2
      (unstable relationships) functioned best in our inpatient sample, whereas
      criterion 9 (stress-related paranoia) performed the poorest. A stepwise logistic
      regression showed that the combination of BPD criteria 2, 1, 6 (unstable affect),
      and 3 (identity) (presented in their order of entry into the regression equation)
      provided the best prediction of group membership (BPD or non-BPD). The results
      suggest that a further refinement of both the BPD criteria set and the diagnostic
      decision rules may be needed.

PMID- 10086474
TI  - The three faces of the antidepressants: a critical commentary on the clinical
      economic context of diagnosis.
AB  - Depression was infrequently diagnosed before the advent of the antidepressants
      but has now apparently become a major public health problem. National campaigns
      are organized aimed at increasing recognition of the condition and at commencing
      treatment for sufferers. Implicit in these approaches is the premise that
      treatment will necessarily reduce disability and ultimately lower suicide rates.
      This is by no means certain. The treatment effect size of many antidepressants is
      modest, the burden of side effects they produce has never been established, and
      data on the quality of life during treatment is absent. It remains possible that
      mild depressive disorders confer a protective effect against suicide and that
      injudicious or unmonitored treatment may increase that risk. In their concern to
      help patients, physicians appear to have systematically overlooked the risks they
      expose patients to as part of their therapeutic effort to minimize the risks
      posed by the patient's condition. Their propensity to overlook the risks posed by
      therapy may stem in part from the availability of antidepressant treatments on
      prescription only. Remedying this situation will require first of all a
      recognition of the biases that prescription-only status introduces into
      therapeutics. Current pharmacological and neuroscientific developments have the
      potential to make alternative health care frameworks possible. Whether these
      alternatives are adopted will probably depend on the capacity of all interested
      parties to reform the present arrangements. Future concepts of depressive
      disorders will probably reflect the regulatory arrangements adopted.

PMID- 10086475
TI  - Polarity sequence, depression, and chronicity in bipolar I disorder.
AB  - Five independent studies show that polarity sequence is associated with prognosis
      in bipolar I disorder. Episodes in which major depression precedes mania (DMI)
      lead to higher morbidity than biphasic episodes which begin with mania (MDI).
      However, little is known about the prognostic significance of polarity sequence
      for long-term outcome. This study examined polarity sequence across multiple
      episodes among 165 bipolar I patients followed prospectively for up to 15 years
      as part of the NIMH Collaborative Study of Depression. Episodes beginning with
      major depression were significantly longer than those beginning with mania for
      the first three prospectively observed episodes when pooling all episode types
      monophasic, biphasic, and polyphasic. Furthermore, affective polarity at onset
      for the first prospectively observed episode was associated with polarity at
      onset for the remaining three episodes. Patients whose first prospectively
      observed episode began with depression had higher overall morbidity during the
      entire follow-up period.

PMID- 10086476
TI  - Social cognition and social skills in schizophrenia: the role of self-monitoring.

PMID- 10086477
TI  - Use of interpreters in Switzerland's psychiatric services.

PMID- 10086478
TI  - Mechanism of action of antidepressant medications.
AB  - The psychopharmacology of depression is a field that has evolved rapidly in just
      under 5 decades. Early antidepressant medications--tricyclic antidepressants
      (TCAs) and monoamine oxidase inhibitors (MAOIs)--were discovered through astute
      clinical observations. These first-generation medications were effective because
      they enhanced serotonergic or noradrenergic mechanisms or both. Unfortunately,
      the TCAs also blocked histaminic, cholinergic, and alpha1-adrenergic receptor
      sites, and this action brought about unwanted side effects such as weight gain,
      dry mouth, constipation, drowsiness, and dizziness. MAOIs can interact with
      tyramine to cause potentially lethal hypertension and present potentially
      dangerous interactions with a number of medications and over-the-counter drugs.
      The newest generation of antidepressants, including the single-receptor selective
      serotonin reuptake inhibitors (SSRIs) and multiple-receptor antidepressants
      venlafaxine, mirtazapine, bupropion, trazodone, and nefazodone, target one or
      more specific brain receptor sites without, in most cases, activating unwanted
      sites such as histamine and acetylcholine. This paper discusses the new
      antidepressants, particularly with regard to mechanism of action, and looks at
      future developments in the treatment of depression.

PMID- 10086479
TI  - Antidepressant effectiveness in severe depression and melancholia.
AB  - While outcome has improved in patients with depressive disorders since the
      introduction of the newer antidepressants, some physicians still treat severely
      depressed patients with the older tricyclic antidepressants because of
      conflicting reports about the efficacy of the newer agents, particularly the
      selective serotonin reuptake inhibitors, in severe depression. However, a
      standardized operational definition of severe depression is lacking, and
      treatment studies are difficult to evaluate due to variation in methodology.
      Remission rates are relatively low in many of the short-term clinical trials of
      the newer antidepressants in severe depression, but may improve if the research
      design were to include a longer trial and aggressive dosing. There is some
      evidence that venlafaxine, a serotonin-norepinephrine antidepressant, may offer
      some advantage for severely depressed patients.

PMID- 10086480
TI  - How should efficacy be evaluated in randomized clinical trials of treatments for
      depression?
AB  - The present system of conducting studies of promising antidepressant therapies
      has evolved through the collaborative efforts of government, industry, and
      academicians and is costly and inefficient. At least one third of the published
      clinical trials of approved antidepressants are negative for efficacy, which can
      be partly explained by the clinical and neurobiological heterogeneity of the
      depressive disorder and partly because of methodological inadequacies.
      Unfortunately, too little attention is given to ensuring the reliability of
      diagnoses and dependent measures, sample sizes are seldom large enough to detect
      modest yet honestly significant differences, and too many trials are pursued
      before dose-response characteristics are fully understood. At present, the only
      data beyond 1 year of treatment--and the only evidence about protection against
      recurrent depression--come during postmarketing or phase 4 of the drug
      development process. Moreover, efficacy data for depressed children and
      adolescents, bipolar depression, psychotic depression, dysthymia, and frail or
      medically ill elderly patients are rarely available at the time a drug is
      introduced. Thus, it is remarkable how little clinicians know about a new
      antidepressant at the time it is first approved for general use. Within a
      research strategy, tactics that ensure reliability, encourage attention to
      adherence, and lessen attrition at the outset of a study will increase the power
      and design sensitivity of a particular trial. Additionally, the issues of
      research funding-including division of the research pie-and the relationship of
      the Food and Drug Administration and investigators to the pharmaceutical industry
      and the National Institute of Mental Health need to be revisited. Finally,
      extension of a compound's patent life might be considered to expand the necessary
      postmarketing research. This article describes the process of conducting the
      clinical trials that support a New Drug Application, discusses issues in
      evaluating efficacy, and offers suggestions for modifying and improving the drug
      development process so that clinicians can better judge new drugs.

PMID- 10086481
TI  - SSRIs and SNRIs: broad spectrum of efficacy beyond major depression.
AB  - Originally studied and introduced for the treatment of depression, the selective
      serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake
      inhibitors (SNRIs) have proven effective for a broad range of psychiatric
      illnesses, including several anxiety disorders, bulimia, and dysthymia. These
      drugs have in common important effects on the serotonergic (5-HT)
      neurotransmission system, which is involved in mediating a substantial number of
      important functions, including mood, aggression, sexual behavior, and pain. In
      addition, some of the new antidepressants, like venlafaxine/venlafaxine XR, also
      have effects on the noradrenergic neurotransmission system, which also appears
      important in mood and anxiety disorders. These new drugs, because of their
      specificity for the serotonin and norepinephrine reuptake proteins, lack most of
      the adverse side effects of tricyclic antidepressants and monoamine oxidase
      inhibitors. Consequently, in addition to being the usual first-line treatments
      for major depression, they are also first-line for panic disorder, obsessive
      compulsive disorder, social phobia, posttraumatic stress disorder, and bulimia.
      They may also be the best medication treatments for dysthymia and generalized
      anxiety disorder. Further advances in psychopharmacology will be driven by
      discoveries from brain imaging and molecular biological research.

PMID- 10086482
TI  - Depression in the medical setting: biopsychological interactions and treatment
      considerations.
AB  - This article examines depression in 6 medical conditions: coronary artery disease
      (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease,
      pain, and the sex hormone changes of aging. Research is beginning to define
      specific biological and psychological mechanisms underlying the adverse
      interactions between depression and these medical conditions. Antidepressant
      medications, psychosocial therapies, and hormonal manipulations are effective in
      reducing depressive symptoms. Specific psychosocial interventions may increase
      longevity in CAD and cancer and may enhance quality of life in HIV infection.
      Newer antidepressants appear to be safer and better tolerated than older agents
      for medically ill patients, but do not appear to be as effective for neuropathic
      pain. Dopamine agonists may benefit depression associated with Parkinson's
      disease. Hormone replacement therapy may improve subsyndromal depressive symptoms
      in postmenopausal women and may enhance antidepressant response for older women
      with major depression.

PMID- 10086483
TI  - Treatment options for refractory depression.
AB  - A significant proportion of patients with depressive disorders do not experience
      a full response with antidepressant treatment. Fortunately, most eventually
      remit, even though the time to response may be significantly delayed in many
      patients. A variety of options exist to deal with these difficult clinical
      situations. Established strategies include switching to an antidepressant of an
      alternative class (e.g., tricyclic to a monoamine oxidase inhibitor [MAOI] or
      selective serotonin reuptake inhibitor [SSRI]), electroconvulsive therapy (ECT),
      and augmentation with lithium or thyroid hormone. Promising alternatives include
      combined serotonin and norepinephrine enhancement strategies (e.g., SSRI plus
      serotonin norepinephrine reuptake inhibitor [NSRI] or higher doses of venlafaxine
      or fluoxetine), steroid suppression therapy, augmentation with atypical
      antipsychotics, and psychotherapy.

PMID- 10086484
TI  - Anterior screw fixation of odontoid fractures.
AB  - BACKGROUND: Anterior screw fixation is the best treatment for odontoid fractures
      when the fracture line is horizontal or oblique downward and backward, as it
      preserves atlantoaxial mobility, especially axial rotation. Some details
      regarding patient positioning and operative technique need to be stressed to
      obtain the best results and avoid complications. METHODS: Between 1989 and 1997,
      we treated 17 cases of odontoid fracture by anterior screw fixation. Only two
      patients presented with motor neurologic deficit. Fracture line was horizontal in
      3 cases and oblique downward and backward in 14 cases. RESULTS: Adequate
      reduction and fixation was obtained in all cases except one, where posterior
      displacement of the screw occurred without neurologic complications. Functional
      result was satisfactory in all cases except two, where we noted significant
      limitation of cervical rotation. CONCLUSION: Successful anterior screw fixation
      gives the best anatomical and functional results for odontoid fractures. Correct
      installation is very important for operative success.

PMID- 10086485
TI  - Postoperative prognosis of Brown-Sequard-type myelopathy in patients with
      cervical lesions.
AB  - BACKGROUND: Postoperative prognosis of the hemihypalgesia in patients with Brown
      Sequard-type myelopathy (BSM) caused by cervical lesions is of great interest to
      surgeons. However, there are very few reports discussing the postoperative
      prognosis of BSM. METHODS: We evaluated the prognosis of BSM using the criteria
      of the Japanese Orthopaedic Association (JOA) score in 16 (seven ossification of
      the posterior longitudinal ligament [OPLL], 5 cervical spondylosis [CS], and 4
      disc herniation patients) out of 233 surgically treated patients with cervical
      diseases. The mean follow-up duration was 2 years and 11 months. RESULTS: After
      surgery, none of these patients showed complete resolution of hemihypalgesia,
      although the most rostral level of hemihypalgesia moved in a caudal direction in
      13 patients (81%), whose recovery ratios of JOA score were significantly better
      than those of hemihypalgesia-level-persisted patients. In our BSM series, OPLL
      occurred most frequently and the anterior element compressing the spinal cord
      existed most frequently in the central area of the vertebra (44%). Postoperative
      improvement in the motor function of the legs in the disc herniation group was
      significantly better than in the OPLL and CS groups (p < 0.05, respectively).
      There were no significant differences in the functional prognosis between the BSM
      and non-BSM patient groups. CONCLUSIONS: BSM patients can expect almost the same
      functional outcome as non-BSM patients, with the exception of the disappearance
      of hemihypalgesia.

PMID- 10086486
TI  - Successful treatment of traumatic acute posterior fossa subdural hematoma: report
      of two cases.
AB  - BACKGROUND: Acute traumatic subdural hematoma of the posterior cranial fossa
      after a closed-head injury, excluding those in newborns, is a very rare clinical
      event. Generally, the outcome is poor and the overall mortality rate is high.
      METHODS: Acute posttraumatic subdural hematomas of the posterior fossa associated
      with acute hydrocephalus in two patients were removed by standard suboccipital
      approach. Preoperatively, one patient was in a coma and the Glasgow Coma Score
      was 9 in another. CT scans showed obliterated mesencephalic cisterns in both
      cases. In the former there was a complex posterior fossa lesion, i.e., combined
      subdural and intracerebellar hematoma. The surgical decompression was completed 3
      and 11 hours after injury, respectively. Intraoperative tapping of the lateral
      ventricle through a burr hole in the occipital area was performed in the latter
      case. RESULTS: Both patients survived; one made a good recovery, (i.e., Glasgow
      Outcome Scale 4 in a patient who was comatose on admission), the other did not do
      as well (GOS 3). CONCLUSIONS: Our experience justifies the policy of mandatory
      early operation in cases of traumatic acute subdural hematoma of the posterior
      fossa associated with poor neurologic condition, even in patients of advanced
      age. In patients with obliterated mesencephalic cisterns and/or complex posterior
      fossa lesions the same approach must be followed. These clinical and CT features
      are not necessarily predictors of a poor outcome.

PMID- 10086487
TI  - Transcranial approach for transsphenoidal encephalocele: report of two cases.
AB  - BACKGROUND: Whereas the transcranial approach has been regarded as the therapy of
      choice for transethmoidal encephalocele, its feasibility for transsphenoidal
      encephalocele has remained controversial, particularly in neonates and infants.
      CASE REPORT: Two cases of transsphenoidal encephalocele operated transcranially
      are presented. In the first case, this 6-year-old boy underwent a transpalatal
      operation with repair of a cleft palate in another hospital before admission.
      Reoperation via the transcranial route was carried out because of postoperative
      recurrent meningitis. With partial resection of the anterior wall, the
      encephalocele could be separated from the underlying tissue, and the interspace
      was filled with the pericranial flap. He made an uneventful recovery and has been
      well for the past 3 years. The second was a 3-month-old baby with a large
      encephalocele filling the nasopharyngeal space. As the cleft palate was absent,
      the transcranial approach was employed. In this case, the herniated tissue was
      excised at the lowest level possible. Postoperatively, panhypopituitarism became
      manifest. Re-evaluation of the preoperative magnetic resonance imaging (MRI)
      disclosed a small mass far below the dorsum sellae, which turned out to be an
      anomalous pituitary gland on histologic examination. CONCLUSIONS: The
      transcranial approach is considered a valid alternative for the therapy of
      transsphenoidal encephalocele, particularly when the transpalatal approach is
      unfeasible. While the anterior wall of the herniated sac may be safely resected,
      the posterior wall should under no circumstances be sacrificed. The preoperative
      MRI is essential, as it may provide valuable information as to the location of
      vital structures within the herniated tissue.

PMID- 10086488
TI  - Exclusive CNS involvement by lymphomatoid granulomatosis in a 12-year-old boy: a
      case report.
AB  - BACKGROUND: Lymphomatoid granulomatosis [LYG] is an angiocentric,
      angiodestructive disease at the higher grade end of the spectrum of angiocentric
      immunoproliferative lesions. It primarily involves the lungs, but it may also
      involve several extrapulmonary sites including the central nervous system (CNS),
      skin, and kidneys. CASE DESCRIPTION: Clinical presentation, radiology and
      treatment of LYG in a 12-year-old male child with multiple intracranial
      extraaxial lesions is described. A 12-year-old boy presented with sudden onset of
      left focal motor seizures with associated history of headache and vomiting.
      Computerized tomographic scan of the brain suggested high-density, bilateral,
      parietal extraaxial lesions. On magnetic resonance imaging, the lesions were iso-
      to hyperintense on T1-weighted images and hyperintense on T2-weighted images. The
      lesions were excised in two stages and histopathological examination confirmed
      the diagnosis. CONCLUSION: LYG seldom involves the CNS exclusively. The present
      case demonstrates exclusive CNS involvement by LYG in a young boy.

PMID- 10086489
TI  - The surgical treatment of pituitary adenomas in the eighth decade.
AB  - BACKGROUND: The surgical treatment of pituitary adenomas in elderly patients
      (i.e., over 70 years of age) is a special problem because of the increased rate
      of perioperative complications and the reduced tolerance of postoperative fluid
      and electrolyte imbalance. Therefore, the unquestionable progress in the
      pharmacological and radiotherapy may not allow these patients the option of
      radical surgical treatment. We report our experience with the transsphenoidal
      procedure for pituitary adenomas in aged patients in an attempt to contribute to
      a better definition of the actual role of surgery. METHODS: Transsphenoidal
      surgery was performed in 11 patients over 70 years of age affected by various
      histological types of pituitary micro- and macroadenomas, ranging from Hardy
      Grade I through IIIc. Special care was dedicated to the postoperative treatment,
      in particular to water and electrolyte balances, and to the immediate treatment
      of any pathological variation of these parameters. RESULTS: We had no mortality
      and no postoperative adjunctive morbidity. All the patients recovered well from
      the operation with an average hospital stay of 20 days. The tumor removal was
      complete in six cases and partial in the remaining five. With an average follow
      up of 2 years, we did observe only one case of symptomatic recurrence of the
      disease. CONCLUSIONS: Transsphenoidal surgery in the elderly is feasible and
      quite safe in the hands of an experienced team, if special care is devoted to the
      preoperative selection of patients and to the postoperative treatment of fluid
      and electrolyte imbalance.

PMID- 10086490
TI  - Stereotactic radiosurgery for anterior foramen magnum meningiomas.
AB  - BACKGROUND: Total microsurgical resection is the procedure of choice for growing
      and symptomatic foramen magnum meningiomas. We hypothesized that for patients
      with advanced age, complicating medical conditions, or residual or recurrent
      meningiomas at the foramen magnum, stereotactic radiosurgery would be a useful
      adjunctive (n = 2) or alternative (n = 3) treatment. METHODS: We report our
      experience in five elderly patients (73-84 years) who underwent gamma knife
      radiosurgery. The median tumor volume was 10.5 ml and the tumor margin dose
      varied from 10 to 16 Gy. Because of the irregular tumor volumes along the
      inferior clivus, multiple isocenters of irradiation were required (range, 2-8;
      mean 4.4). RESULTS: During the follow-up interval of 1-5 years (median, 3 years),
      one patient died of an intercurrent illness, and all remaining patients were
      stable without any further deterioration in their clinical condition. Follow-up
      imaging studies revealed a reduction in tumor volume in one patient and no
      further growth in the remaining four. CONCLUSION: We believe that stereotactic
      radiosurgery provides safe and effective management for patients who are poor
      candidates for resection of their foramen magnum meningiomas.

PMID- 10086491
TI  - Multiple skull base meningioma: case report.
AB  - BACKGROUND: The incidence of multiple skull base meningiomas varies from 1 to 3%
      in different series. Skull base meningiomas are rare. The pathogenetic role of
      low-dose radiation seems to be fairly well established in the oncogenesis of
      meningiomas. Calvarial location and multiplicity seem to be among the distinctive
      features of radiation-induced meningiomas. Skull base location is a very rare
      occurrence, mainly because the path of irradiation does not significantly involve
      this region. CASE REPORT: We describe a rare case of simultaneous occurrence of
      two skull base meningiomas in a 66-year-old female. This patient underwent low
      dose irradiation for tinea capitis when she was 8 years old. The patient
      complained of nuchal pain, paresthesias in both hands, and progressive weakness
      on her right side. She was admitted to the hospital in September 1994. An MRI
      showed two masses, one located at the level of the tuberculum sellae and the
      other at the foramen magnum. These seemed very likely to be multiple meningiomas.
      The latter lesion, which was more symptomatic and dangerous, was operated on
      first. Six months later, elective treatment of the suprasellar meningioma was
      performed with success. CONCLUSION: The actual role of previous head irradiation
      in the oncogenesis of the present meningiomas remains somewhat unclear. Proper
      management and judicious use of skull base surgery techniques were key factors in
      the successful treatment of the patient.

PMID- 10086492
TI  - Cerebellar clear cell ependymoma mimicking hemangioblastoma: its clinical and
      pathological features.
AB  - BACKGROUND: As the clinical and pathological significance of cerebellar clear
      cell ependymoma (CCE) has not been recognized in the past, eight cases of
      cerebellar CCEs were studied. METHODS: Subjects were six men and two women, and
      their ages ranged from 23 to 64 years old. Their neuroradiological, operative,
      and pathological features were reviewed. RESULTS: The tumors frequently showed
      high vascularity on angiography and marked enhancement on computerized
      tomography. Grossly, six tumors exhibited a "cyst with mural nodule" and two were
      mostly solid containing small cysts. At operation, the tumor nodules were dark
      red in color and the cysts contained xanthochromic fluid. Microscopically, all
      tumors displayed mostly clear round cells and abundant blood vessels. Although
      they commonly lacked the characteristic features of ependymomas, immunostaining
      and electron microscopy confirmed their ependymal origin. CONCLUSIONS: The
      results indicate that cerebellar CCEs closely mimic hemangioblastoma both
      clinically and pathologically, which suggests CCE should be considered in the
      differential diagnosis of vascular tumors of the cerebellum. Some diagnostic
      clues to differentiate CCE from hemangioblastoma are discussed.

PMID- 10086493
TI  - Complete response of a large brain metastasis of renal cell cancer to interferon
      alpha: case report.
AB  - BACKGROUND: Interferon-alpha (IFNalpha) is a drug widely used in the treatment of
      metastatic renal cell cancers, especially lung lesions. Successful treatment
      using IFNalpha for histologically proven brain metastasis has not been reported.
      CASE REPORT: A large pineal tumor was found in a 51-year-old man with renal cell
      cancer in the left kidney. The histological diagnosis of biopsied specimens was a
      brain metastasis from renal cell cancer. The patient was treated with
      intramuscular injections of IFNalpha. The brain metastasis gradually decreased in
      size and disappeared completely 6 months after the initial injection of IFNalpha.
      The IFNalpha therapy was continued for 9 months. Fifteen months later, no
      recurrence was evident on brain magnetic resonance imaging. CONCLUSION: This is
      an extremely rare case in which the long-term use of IFNalpha induced a complete
      response of a brain metastasis from renal cell cancer.

PMID- 10086494
TI  - Graphic analysis of microscopic tumor cell infiltration, proliferative potential,
      and vascular endothelial growth factor expression in an autopsy brain with
      glioblastoma.
AB  - BACKGROUND: Growth of brain tumors requires tumor-cell attachment to adjacent
      structures, degradation of surrounding matrixes, migration of tumor cells,
      proliferation of vasculature, and tumor cell proliferation. Comparison of the
      findings on neuroimaging, degrees and patterns of tumor invasion, regional tumor
      cell viability detected by Ki-67 immunohistochemistry, and regional vascular
      endothelial growth factor (VEGF) expression in whole-brain specimen of
      glioblastoma therefore is of great interest, and will facilitate study of the
      host reaction against the glioblastoma. METHODS: We graphically analyzed
      microscopic tumor-cell infiltration, regional differences in Ki-67 labeling
      indices (LI), and immunohistochemical expression of VEGF in an autopsy brain with
      glioblastoma. RESULTS: Glioblastoma cells infiltrated the brain far beyond the
      gross limits of the tumor and the areas with high signal intensity on T2-weighted
      magnetic resonance images. A wide range of histologic malignancy was apparent
      from hematoxylin-eosin staining and the Ki-67 labeling indices. VEGF was highly
      expressed in normal astrocytes located outside the tumor. CONCLUSION: Graphic
      analysis of histologic and immunohistochemical patterns is a useful method of
      investigating the mechanisms of glioma growth, tumor cell infiltration in the
      brain, and the host reaction of the brain against neoplasms.

PMID- 10086495
TI  - Clinical usefulness of and problems with three-dimensional CT angiography for the
      evaluation of arteriosclerotic stenosis of the carotid artery: comparison with
      conventional angiography, MRA, and ultrasound sonography.
AB  - BACKGROUND: Prevention of stroke is aided by determination of the degree of
      carotid artery stenosis and progression of arterial sclerosis. Three-dimensional
      computed tomography (CT) angiography (3D-CTA) is a new method for evaluating the
      degree of arterial stenosis. The purpose of this study was to compare the
      accuracy of 3D-CTA with the "gold standard": conventional angiography, magnetic
      resonance angiography (MRA), and ultrasound sonography (US). METHODS: A total of
      128 carotid bifurcations in 64 patients (42 men and 22 women; mean age, 68.5
      years) were examined by 3D-CTA because of symptoms of cerebral infarction,
      carotid bruit, or findings suggestive of arteriosclerotic carotid artery stenosis
      on MRA screening. The following were used to compare 3D-CTA with conventional
      angiography, MRA and US: 1) estimation of the degree of stenosis; 2) depiction of
      irregularities in arterial walls, including calcification, intimal thickening,
      ulcers and plaque; and 3) surgical planning for carotid endarterectomy (CEA) and
      percutaneous transluminal angioplasty (PTA), and postoperative evaluation.
      RESULTS: A strong correlation was found between the degrees of stenosis estimated
      by conventional angiography and 3D-CTA MIP image (r = 0.987/p < 0.0001). On the
      other hand, stenosis was generally overestimated by MRA, which, however, has the
      advantage of being able to scan the carotid siphon to the middle cerebral artery
      at one time. Calcification and ulceration of the artery wall could be evaluated
      with 3D-CTA, whereas with US, progression of arterial sclerosis could be
      evaluated by differentiation of homogenous and heterogenous plaque. The
      anatomical relationships between the site of stenosis and the internal jugular
      vein and bony structures, which must be known before CEA, were confirmed by
      observation of rotated images using the shaded surface reconstruction (SSR)
      method. Because the hemodynamics of cross and collateral flows cannot be clearly
      imaged with 3D-CTA, standard angiography is needed to determine suitability for
      bypass surgery. CONCLUSIONS: The current method used in our hospital for the
      diagnosis of stenosis of the internal carotid artery includes MRA or US for
      initial screening, 3D-CTA for evaluation of the degree of stenosis and for
      preoperative and postoperative evaluation of CEA and PTA, and conventional
      angiography for evaluation of hemodynamics and determination of the indications
      for a bypass surgery.

PMID- 10086496
TI  - Severe stenosis of the internal carotid artery presenting as loss of
      consciousness due to the presence of a primitive hypoglossal artery: a case
      report.
AB  - BACKGROUND: Symptoms of ischemic attacks in the internal carotid system usually
      involve focal cerebral dysfunction, i.e., hemiparesis or aphasia. However, an
      ischemic attack in the vertebrobasilar artery system usually presents with
      combined symptoms. The variety of manifestations included in the vertebrobasilar
      profile makes the potential pattern of symptoms considerably more variable and
      complex than that in the carotid system. Manifestations can include syncope and
      also vertigo. METHOD AND RESULTS: A 42-year-old woman experienced frequent
      attacks of faintness with vertigo. Angiography demonstrated severe stenosis of
      the left internal carotid artery with a persistent primitive hypoglossal artery
      just distal to the stenosis. The right internal carotid artery was normal and
      cross circulation through the anterior communicating artery was not well
      developed. Both vertebral arteries were hypoplastic. The patient underwent
      carotid endarterectomy and, thereafter the episodes of syncope completely
      disappeared. CONCLUSION: It was supposed that global ischemia including the brain
      stem occurred because of stenosis of the left internal carotid artery
      attributable to the presence of a primitive hypoglossal artery.

PMID- 10086497
TI  - Embolectomy for acute embolic occlusion of the internal carotid artery
      bifurcation.
AB  - BACKGROUND: Acute occlusion of the distal intracranial segment of the internal
      carotid artery (ICA) causes sudden severe hemispheric ischemia. A low rate of
      recanalization and a high mortality rate for this condition have been noted, even
      with endovascular treatment. METHODS: We report the results of emergency
      embolectomy in six patients with acute embolic occlusion of the internal carotid
      artery (ICA) bifurcation. All six patients were admitted to our institute within
      2 h of the onset of symptoms. Computed tomography (CT) scans on admission
      revealed no low-density or high-density regions in any patients. The time between
      onset of symptoms and completion of angiography ranged from 2 to 4 h (2.8 +/- 0.7
      h). RESULTS: Emergency embolectomy was performed for each patient. Recanalization
      was confirmed angiographically in four of the patients. In the remaining two
      patients, massive infarction in the territory of the ICA was detected on the CT
      scans obtained the day of the operation, and postoperative angiography was not
      performed in these two cases. These two patients died of uncal herniation 6 days
      after onset. Two of the six patients were able to walk with a cane 2 months after
      surgery. The remaining two patients were unable to walk or attend to their own
      bodily needs without assistance. The time elapsed between onset of symptoms to
      reopening of the occluded vessel was within 6 h in the four surviving patients.
      The recanalization rate was 66.7% (4/6) for the embolectomy procedure,
      significantly higher than that (12.5%) of the thrombolytic therapy reported in a
      previous study. CONCLUSIONS: In summary, open embolectomy can be performed when
      the time after onset of symptoms is less than 6 h.

PMID- 10086498
TI  - Cerebrovascular reactivity before and after carotid endarterectomy.
AB  - BACKGROUND: The hemodynamic relevance of internal carotid artery (ICA) stenosis
      often does not correlate with anatomic features, as angiographically defined. The
      cerebrovascular reactivity (CVR) has been advocated as a means of defining the
      cerebral hemodynamic impairment. METHODS: We assessed the results of pre- and
      postoperative CVR evaluation, using the CO2 transcranial doppler method, in 25
      patients with high-grade ICA stenosis. The patients with history of stroke,
      evidence of cerebral CT infarction or symptoms from the contralateral circulation
      or the brain stem were excluded to avoid the effects of cerebral infarction on
      the hemodynamic studies. Statistical analysis was used to evaluate the CVR
      changes after carotid endarterectomy. RESULTS: Preoperative evaluation showed
      that CVR was generally well correlated with the degree of ICA stenosis and
      concomitant contralateral carotid steno-occlusion. Before endarterectomy the mean
      CVR value was 66.5% (moderately reduced). After surgery the overall mean value of
      CVR was 84.1% (normal), with a statistically significant improvement. CONCLUSION:
      The results of this study suggest that the CVR evaluation allows one to obtain
      hemodynamic information of clinical interest in the patients with ICA stenosis
      and that carotid endarterectomy is effective to restore the CVR in patients with
      cerebral hemodynamic impairment.

PMID- 10086499
TI  - Thyrocervical to vertebral artery transposition and ipsilateral carotid
      endarterectomy.
AB  - BACKGROUND: We report a new method for treating patients with symptomatic high
      grade stenosis of the proximal vertebral artery associated with high-grade
      stenosis of the ipsilateral carotid artery. METHODS: Our patient had high-grade
      stenosis of the proximal right vertebral artery as well as high-grade stenosis of
      the ipsilateral carotid artery and suffered continued posterior circulation
      ischemic neurological deficits despite anticoagulation. RESULTS: The patient was
      successfully treated with a carotid endarterectomy and thyrocervical-to-vertebral
      artery transposition in a single operation. CONCLUSION: This procedure has the
      advantage in this setting of avoiding additional cross clamping on the diseased
      carotid artery that would normally be required for the vertebral-to-carotid
      artery transposition with carotid endarterectomy. Also, thrombosis at one
      anastamosis site would not endanger the other site as well.

PMID- 10086500
TI  - The simple indicator for revascularization of acute middle cerebral artery
      occlusion using angiogram and ultra-early embolectomy.
AB  - BACKGROUND: The purpose of the study was: (1) to find a clinical indicator for
      revascularization of acute middle cerebral artery (MCA) occlusion using
      angiograms of 100 patients examined immediately after onset and treated medically
      and (2) to investigate 10 ultra-early MCA embolectomies. METHODS: Quantity of
      collateral circulation, based on time required for conduction of contrast media
      to the insular portion of the MCA from the anterior cerebral artery, MCA
      conduction time (MCT) was graded as: Grade 1: In the arterial phase, there was
      conduction not only to the insular portion of the MCA but also to proximal M2;
      Grade 2: Conduction to the insular portion was present in late arterial phase;
      Grade 3: Conduction was present in capillary phase; Grade 4: Conduction was
      present in venous phase; Grade 5: No conduction was seen. The results of
      embolectomy are discussed. RESULTS: MCT can predict the extent of resultant low
      density area on computed tomographic scan. For Grades 3, 4, or 5, embolectomy
      could be considered superior to medical treatment, if the low-density area was
      localized in the basal ganglia or centrum semiovale after surgery. Consequently,
      embolectomy was effective in four cases recanalized within 6 hours of onset.
      Except for one Grade 5 case, the remaining nine cases showed neither lethal
      hemorrhagic infarction nor brain edema. Overall outcome was significantly better
      than cases treated medically (p < 0.05), but some cases did not recover from
      hemiparesis due to infarcts in the area of the lenticulostriate arteries.
      CONCLUSIONS: MCT helps to predict the applicability of revascularization of acute
      MCA occlusion. Efficacy of embolectomy depends on revascularization within 6
      hours of onset. Even after complete MCA flow restoration, infarcts in the area of
      the lenticulostriate arteries cannot always be prevented.

PMID- 10086501
TI  - Omental transposition for cerebral infarction: a 13-year follow-up study.
AB  - BACKGROUND: During the past decade there has been increasing use of omental
      transposition to the brain of patients who experienced neurologic sequelae after
      a cerebral infarction. This paper reports the long-term neurologic effects seen
      in a patient who underwent omental transposition 31 months after a stroke. Her
      postoperative follow-up period has been 13 years. CASE DESCRIPTION: The patient
      had an expressive aphasia, a right hemiparesis and the inability to read which
      occurred immediately after her stroke. After surgery she demonstrated subjective
      and objective improvement in her speech and mobility. She also regained her
      ability to read shortly after surgery. CONCLUSION: The patient demonstrated that
      omental transposition to the brain can improve neurologic function in the
      presence of a long-standing cerebral infarction and that the clinical improvement
      can be maintained over an extended period.

PMID- 10086502
TI  - The business of surgery: operations management and strategic planning. Part II:
      Preoperative planning.

PMID- 10086503
TI  - Spinal epidural hematoma following MI.

PMID- 10086504
TI  - Fibrin glue for cranial defects.

PMID- 10086505
TI  - Hepatic mitochondrial toxicity from nucleoside analog therapy.

PMID- 10086506
TI  - The autopsy as a performance measurement tool--diagnostic discrepancies and
      unresolved clinical questions: a College of American Pathologists Q-Probes study
      of 2479 autopsies from 248 institutions.
AB  - OBJECTIVE: To develop a multi-institutional reference database for quality
      improvement purposes using the autopsy to define clinical diagnostic
      discrepancies and resolve clinical questions. DESIGN: Using the College of
      American Pathologists Q-Probes format, institutions prospectively assessed a
      maximum of 15 consecutive autopsies each, excluding forensic cases and stillborn
      infants, conducted over a 6-month period. They documented answers to clinical
      questions provided at autopsy and classified unexpected disease diagnoses
      according to a standardized system. SETTING AND PARTICIPANTS: Hospital-based
      autopsies performed at 248 institutions participating in the 1993 College of
      American Pathologists Q-Probes Quality Improvement Program. MAIN OUTCOME
      MEASURES: Percentages of clinical questions resolved by the autopsy and
      percentage of autopsies with unexpected findings of graded clinical impact.
      RESULTS: In the aggregate database of 6427 questions from 2479 autopsies, overall
      93.0% were answered by the autopsy. The 3 most common question categories were
      (1) identify pathology to account for clinical signs or symptoms (28.0%); (2)
      establish the cause of death (21.0%); and (3) confirm a clinical diagnosis
      (19.0%). At least one major unexpected disease finding that contributed to the
      patient's death was discovered in 39.7% of the total number of autopsies. There
      were no differences in the percentages of autopsies with these major unexpected
      findings when the data were stratified by institutional demographics or decedent
      characteristics. CONCLUSION: This multi-institutional study underscores the
      clinical relevance of postmortem examination in current medical practice by
      consistently providing answers to unresolved clinical questions and frequently
      revealing major unexpected findings that contributed to the patient's death. It
      is our strong belief that this postmortem-derived clinicopathologic information
      is a key indicator of effectiveness of care. Integration of this information into
      institutional quality improvement programs will improve system processes and
      clinician performance.

PMID- 10086507
TI  - A method for proficiency testing of small peer groups in the College of American
      Pathologists Coagulation Surveys.
AB  - OBJECTIVE: To develop a grading scheme for the proficiency testing of small peer
      groups of fewer than 10 members for the prothrombin time (PT) and activated
      partial thromboplastin time (APTT). METHODS: A modified target value for small
      peer groups was derived based on the assumption that measurement variability in
      the PT and APTT is more greatly influenced by variations in reagents than in
      instruments. Criteria for grading were established by statistical simulation to
      achieve misclassification errors of less than 5% for both incorrectly passing and
      failing participants. College of American Pathologists Coagulation Survey data
      were analyzed to determine the number of additional laboratories graded using the
      proposed scheme, as well as the failure rates among participants in the small
      peer groups. RESULTS: The modified target value for small peer groups is a
      weighted average between the mean of the peer group and the mean of all
      participants using the same reagent (reagent group). Peer groups with as few as 4
      members can be graded provided that specific criteria are satisfied: there must
      be at least 5 peer groups for the same reagent, at least 3 of these 5 peer groups
      must have more than 3 members, and the coefficient of variation for the reagent
      group must be less than 10%. This proposed grading scheme decreased the number of
      ungraded laboratories by 44% to 46% for the PT and 42% to 55% for the APTT. The
      percentage of failing grades among participants in the small peer groups ranged
      from 1.3% to 4.1% for the PT and 1.4% to 7.2% for the APTT. These failure rates
      were 2.8- to 13.0-fold higher than the failure rates in large peer groups (P < or
      = .05). CONCLUSIONS: The proposed small peer group grading scheme can improve the
      effectiveness of College of American Pathologists proficiency testing for the PT
      and APTT and may also be generally applicable to other test methods and analytes.

PMID- 10086508
TI  - Flow cytometric immunophenotyping of bone marrow core biopsies: report of 8
      patients with previously undiagnosed hematologic malignancy and failed bone
      marrow aspiration.
AB  - OBJECTIVE: To report a method for flow cytometric immunophenotyping (FCI) bone
      marrow (BM) core biopsies in patients with hematologic malignancies of the BM who
      present with a failed BM aspiration ("dry tap"). DESIGN AND SETTING: Core biopsy
      specimens of BM were obtained from 8 patients who presented with previously
      undiagnosed hematologic malignancies arising in (7 cases) or secondarily
      involving (1 case) the BM and a dry tap. Suspensions of the BM core biopsy
      specimens were prepared and analyzed by FCI methods. DATA EXTRACTION AND DATA
      SYNTHESIS: The FCI data were analyzed in conjunction with cytomorphologic,
      histologic, immunohistochemical, and cytogenetic findings in all cases to
      determine a final diagnosis. CONCLUSIONS: The prepared BM core suspensions were
      viable and allowed for a complete immunophenotype profile by FCI in all cases,
      resulting in a clear definition of the cell of origin of the hematologic
      malignancy. Because of lack of preservation of architectural features and the
      potential for artifactual alterations of the relative frequency of abnormal
      cells, the FCI data must always be correlated with histologic sections of the BM
      biopsy.

PMID- 10086509
TI  - Protease expression in dedifferentiated parosteal osteosarcoma.
AB  - BACKGROUND: Parosteal osteosarcoma with dedifferentiation provides a useful model
      to study tumor progression from an indolent locally aggressive neoplasm to highly
      lethal metastasizing malignancy. Up-regulation of the proteolytic enzymes
      participating in stromal degradation is known to promote invasive growth and
      metastasis of several human and experimental tumors. METHODS: The expression
      patterns of urokinasase plasminogen activator (u-PA), its cell-surface receptor
      (u-PAR), and cathepsin B were analyzed by immunohistochemical techniques in 11
      cases of parosteal osteosarcoma and in 4 cases of dedifferentiated parosteal
      osteosarcoma. RESULTS: Both enzymes and the receptor were coexpressed in most
      tumor cells of parosteal and dedifferentiated parosteal osteosarcoma. Their
      expression was strikingly enhanced in the dedifferentiated high-grade component
      of the tumors. Tumor cells involved in bone production (ie, those adjacent to
      tumor produced bone trabeculae) exhibited equally strong expression of u-PA, u
      PAR, and cathepsin B, regardless of their histologic grade. Expression of u-PA, u
      PAR, and cathepsin B was undetectable in the "normalized" cells embedded in the
      well-developed tumor bone trabeculae. CONCLUSION: These data indicate that u-PA
      and its interacting molecules, such as u-PAR and cathepsin B, may have some
      contributory effects on the metastatic potential of tumor cells in
      dedifferentiated parosteal osteosarcoma.

PMID- 10086510
TI  - Sessile polypoid gastric heterotopia of rectum: a report of 2 cases and review of
      the literature.
AB  - OBJECTIVE: The term heterotopia, a term derived from Greek, implies "other
      place." It refers to the finding of normal tissues at foreign sites. Heterotopic
      gastric tissue rarely involves the large bowel. We report 2 cases of this rare
      entity. DATA SOURCES: Case reports of 2 patients with sessile polypoid lesion in
      the rectum, with a review of the available literature, using both MEDLINE and
      relevant bibliographies of published articles. RESULTS: Biopsies of the rectal
      lesions in our 2 cases revealed the presence of gastric tissue. Only 27 other
      such cases have been reported in the English literature. CONCLUSIONS: Patients
      with rectal gastric heterotopia usually present with bleeding, but other
      presentations and complications are possible. Endoscopic or surgical excision is
      the treatment of choice, although the lesions also respond to histamine 2
      receptor blockers.

PMID- 10086511
TI  - Androgen insensitivity syndrome: an immunohistochemical, ultrastructural, and
      morphometric study.
AB  - OBJECTIVE: To evaluate the morphometric, immunohistochemical, and ultrastructural
      lesions of the testes in prepubertal and adult patients with androgen
      insensitivity syndrome. METHODS: We examined the testicular biopsy using
      immunohistochemistry for vimentin, smooth muscle actin, and collagen IV antigens.
      Quantification of seminiferous tubules and testicular interstitium was performed
      in prepubertal and adult patients with androgen insensitivity syndrome and
      results were compared with normal testes from both infants and adults. RESULTS:
      The adult testes presented nodular and diffuse lesions that consisted of Sertoli
      cell-only seminiferous tubules. Two types of Sertoli cells could be
      distinguished, namely, immature vimentin-positive Sertoli cells and nearly mature
      Sertoli cells. In the nodules, the lamina propria was thin and contained a scant
      number of actin-positive peritubular cells. Leydig cells were hyperplastic. The
      prepubertal patients showed only diffuse lesions characterized by Sertoli cell
      hyperplasia, decreased germ cell numbers, and a discontinuous immunoreaction to
      collagen IV. CONCLUSIONS: The testicular lesions in androgen insensitivity
      syndrome are probably caused by primary alterations that begin during gestation.
      These lesions become progressively more pronounced at puberty, when the nodular
      lesion pattern (adenomas) is completely developed.

PMID- 10086512
TI  - Determinants of plasma fibrin D-dimer sensitivity for acute pulmonary embolism as
      defined by pulmonary angiography.
AB  - BACKGROUND: The reported operating characteristics of the plasma fibrin D-dimer
      level for the diagnosis of acute pulmonary embolism vary widely. OBJECTIVE: To
      determine the sensitivity, specificity, predictive value, and clinical utility of
      the D-dimer for the diagnosis of pulmonary embolism, and to describe the effect
      of D-dimer assay method (enzyme-linked immunosorbent assay [ELISA], latex
      agglutination, membrane ELISA) and discriminate level, patient location at onset,
      comorbid disease, duration and intensity of concurrent heparin administration,
      and duration of symptoms on these operating characteristics. DESIGN: Prospective
      laboratory investigation. SETTING: Community and tertiary care teaching hospital.
      PATIENTS: Consecutive patients with suspected acute pulmonary embolism referred
      for pulmonary angiography from April 1993 through March 1996. MEASUREMENTS:
      Baseline characteristics, the duration and intensity of heparin anticoagulation,
      the time interval between symptom onset and plasma D-dimer testing, pulmonary
      angiography, and the D-dimer level on the day of pulmonary angiography. RESULTS:
      Of 105 consenting patients, 33 (31%) had a positive pulmonary angiogram. The D
      dimer sensitivity/ negative predictive value for the ELISA, latex agglutination
      (American Bioproducts Co/Diagnostica Stago and Biopool International), and
      membrane ELISA were 100%/100%, 94%/94%, 100%/100%, and 97%/96%, respectively, at
      a discriminate level of 250 microg/L or less. The clinical utility, defined as
      the prevalence of a negative test, ranged from 17% to 33%. D-dimer sensitivity
      was unaffected by patient location at onset, comorbid disease, or heparin therapy
      but was inversely related to the duration of symptoms. CONCLUSIONS: The
      sensitivity of the plasma fibrin D-dimer for the diagnosis of pulmonary embolism
      depends on the assay method, the assay-specific discriminate level, and the
      duration of symptoms. At the appropriate discriminate level, the plasma D-dimer
      is a sensitive but nonspecific test for the diagnosis of pulmonary embolism.

PMID- 10086513
TI  - Intrapericardial yolk sac tumor associated with acute myocarditis.
AB  - An occult intrapericardial yolk sac tumor occurred in a 3-year-old girl with a
      fatal outcome. At autopsy, a 5.5-cm mass surrounded the base of the heart and
      compressed the left atrium posteriorly. Histologically, the tumor was a pure yolk
      sac tumor. Postmortem chemical analyses of the blood revealed an alpha
      fetoprotein level greater than 7000 microg/L. Acute myocarditis of both
      ventricles was also found.

PMID- 10086514
TI  - Ossified intratesticular mucinous tumor.
AB  - We report a case of an ossified primary intratesticular mucinous tumor in a 69
      year-old man, which was discovered incidentally during a consultation for
      erectile dysfunction. The 7.5 x 4.8 x 4-cm, predominantly solid, and partially
      cystic mass completely replaced the testis with no extension to tunica albuginea
      and epididymis. The multiloculated area was mostly covered by a single layer of
      bland mucinous epithelium with few areas of epithelial tufting, stratification,
      and nuclear atypia. The solid areas consisted of mature bone and fibrous stroma
      with cholesterol clefts, some multinucleated giant cells, moderate infiltration
      of lymphocytes, and foamy vacuolated macrophages. The bone showed occasional
      rimming of osteoblasts and rare osteoclasts. Rare foci of mature bone were found
      in the nonfibrosed wall and lumen cysts. The patient is alive and well 3 years
      after right orchiectomy with spermatic cord resection.

PMID- 10086515
TI  - Composite ganglioglioma and dysembryoplastic neuroepithelial tumor.
AB  - Both ganglioglioma and dysembryoplastic neuroepithelial tumors are well
      recognized glial-neuronal neoplasms associated with chronic epilepsy and cortical
      dysplasia (neuronal migration abnormalities). The exact relationship between
      these 2 glial-neuronal tumors continues to be debated. This article reports a
      case of a composite ganglioglioma and dysembryoplastic neuroepithelial tumor
      occurring in a 36-year-old woman in the left temporal lobe region. The resection
      histologically demonstrated distinct areas of ganglioglioma and dysembryoplastic
      neuroepithelial tumor. A focal area of cortical dysplasia is also identified. The
      MIB-1 labeling indexes in both components were low (<1% of tumor cell nuclei).
      The coexistence of these 2 lesions and cortical dysplasia suggest a possible
      etiologic relationship between these 2 tumors.

PMID- 10086516
TI  - Severe intrahepatic cholestasis caused by amiodarone toxicity after withdrawal of
      the drug: a case report and review of the literature.
AB  - Cholestasis has been reported as a rare presentation among patients with severe
      liver injury secondary to amiodarone hepatic toxicity. We report an unusual case
      of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had
      been discontinued and the initial abnormal liver function findings had improved.
      The patient, without jaundice at the initial presentation, developed severe
      jaundice about 4 months after withdrawal of amiodarone. Light and transmission
      electron microscopic examination of a specimen secured by computed
      tomographically guided liver biopsy was consistent with amiodarone hepatic
      toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound,
      endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and
      computed tomographic scans of the abdomen all failed to demonstrate any other
      causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic
      toxicity may occur after drug withdrawal even if results of liver function tests
      improve. Histopathologic examination of a liver biopsy specimen is of value for
      diagnosis and prognosis. The liver biopsy findings, clinical course, and liver
      function test results are discussed, and the English-language literature on
      amiodarone cholestatic hepatotoxicity is reviewed.

PMID- 10086517
TI  - Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case
      with T-cell phenotype.
AB  - We describe a case of primary effusion lymphoma with T-cell phenotype, mixed
      genotype, and intranuclear herpesvirus inclusions visible with the light
      microscope. Cells were studied by immunohistochemical analysis, in situ
      hybridization, immunoglobulin and T-cell receptor gene rearrangement, and
      polymerase chain reaction. Primary effusion lymphoma cells with T-cell phenotype
      revealed herpesvirus 8 inclusions predominantly seen in apoptotic cells,
      suggesting that productive viral infection is associated with cell death.
      Clinical features were typical of primary effusion lymphoma. Cytologic, molecular
      genetic, and phenotypic features demonstrated a unique variant of primary
      effusion lymphoma.

PMID- 10086518
TI  - Klinefelter syndrome.

PMID- 10086519
TI  - Thymic neuroendocrine tumors: a commentary with current perspectives on
      neuroendocrine neoplasia.

PMID- 10086520
TI  - Carpentier-Edwards standard and supraannular porcine bioprostheses: comparison of
      technology.
AB  - BACKGROUND: Performance with regard to structural valve deterioration (SVD) with
      the Carpentier-Edwards standard (CE-S) and supraannular (CE-SAV) (Baxter
      Healthcare Corp, Irvine, CA) porcine bioprostheses was evaluated to determine
      whether progress in reduction of structural failure has been achieved with
      technological changes. METHODS: The CE-S was implanted during 567 aortic valve
      replacement (AVR) and 486 mitral valve replacement (MVR) procedures, and the CE
      SAV was implanted during 1,670 AVR and 1,096 MVR procedures. The failure mode of
      early stent dehiscence with the CE-SAV prosthesis, thought to be controlled by
      manufacturing changes in 1986 and 1987, supported comparison of the CE-SAV with
      censored cases of stent dehiscence. Stent dehiscence accounted for only 1.2% (1
      of 81) and 14.1% (29 of 205) of AVR and MVR CE-SAV failures, respectively.
      RESULTS: The only difference for AVR for freedom from SVD occurred in the 21- to
      40-year age group at 15 years and was 68% for the CE-SAV and 31% for the CE-S
      (p<0.05). In the 61- to 70-year age group, freedom from SVD at 15 years was 76%
      for the CE-S and 84% for the CE-SAV; for the 71-year or higher age group, freedom
      from SVD was 89% and 95%, respectively (p = NS). For MVR freedom from SVD was
      different only in the 71-year or higher age group and was 90% for the CE-S and
      59% for the CE-SAV (p<0.05). Freedom from SVD was reduced but was similar (p =
      NS) for the other age groups. For AVR the actual freedom from SVD at 15 years for
      the CE-S and CE-SAV was, respectively, 79% and 72% for the 51- to 60-year age
      group, 86% and 91% for the 61- to 70-year age group, and 98% and 98% for the 71
      year or higher age group. For MVR, these rates were, respectively, 69% and 75%
      for the 61- to 70-year age group and 96% and 89% for the 71-year and higher age
      group. CONCLUSIONS: The technologic advancements made in the second-generation CE
      SAV bioprosthesis to reduce the incidence of structural failure have not
      uniformly been successful. The actual freedom from SVD provides evidence for
      implantation of porcine bioprostheses for AVR in age groups 61 to 70 years and 71
      years or higher and for MVR in the age group 71 years or higher.

PMID- 10086521
TI  - Modulation of coronary perfusion pressure can reverse cardiac dysfunction after
      brain death.
AB  - BACKGROUND: Brain death results in a rapid decline in left ventricular function,
      which has clinical relevance for organ transplantation. The aim of the present
      study was to investigate coronary perfusion changes during brain death and their
      role in cardiac dysfunction. METHODS: In an in situ isolated canine heart model,
      brain death was induced by inflation of a subdural balloon catheter. The heart
      was perfused separately with the animal's own blood by a pressure-controlled
      roller pump that was coupled to the measured aortic pressure. Myocardial
      contractility was estimated by the slope of the end-systolic pressure-volume
      relation. RESULTS: Induction of brain death resulted in a transient hyperdynamic
      response, followed by a significant decrease in systemic vascular resistance,
      coronary blood flow, and the end-systolic pressure-volume relation (p<0.05).
      However, if coronary perfusion pressure was decoupled from aortic pressure and
      elevated to pre-brain death levels, coronary blood flow and the end-systolic
      pressure-volume relation were also restored to baseline levels. CONCLUSION:
      Severe impairment of coronary blood flow may contribute to decreased
      contractility after brain death that can be reversed by modulation of coronary
      perfusion pressure.

PMID- 10086522
TI  - Radial approach: a new concept in surgical treatment for atrial fibrillation I.
      Concept, anatomic and physiologic bases and development of a procedure.
AB  - BACKGROUND: The maze procedure cures atrial fibrillation; however, it isolates
      the pulmonary vein area and results in discordant activation in certain adjacent
      left atrial segments, which affects left atrial function. To preserve a more
      physiologic atrial transport function, we developed a new concept of surgical
      treatment for atrial fibrillation-the radial approach. The atrial incisions
      radiate from the sinus node toward the atrioventricular annular margins to allow
      a more physiologic atrial activation sequence and parallel the atrial coronary
      arteries to preserve blood supply to most atrial segments. METHODS: We examined
      the atrial coronary arteries and the activation sequence during sinus rhythm in
      normal canine hearts to design the atrial incisions according to the concept of a
      radial approach. RESULTS: The pattern of coronary artery distribution was
      centripetal, branching from the right coronary or left circumflex coronary artery
      at the right or left atrioventricular groove and spreading toward the sinus node.
      The endocardial mapping of the atria disclosed some important findings in
      designing the atrial incisions of the radial approach: the activation sequence at
      the left atrial septum and at the posterior left atrium between the pulmonary
      vein orifices. The atrial incisions were designed according to these findings.
      CONCLUSIONS: The radial approach may represent a more physiologic atrial
      transport function.

PMID- 10086523
TI  - Radial approach: a new concept in surgical treatment for atrial fibrillation. II.
      Electrophysiologic effects and atrial contribution to ventricular filling.
AB  - BACKGROUND: In a previous study the atrial incisions that follow the concept of
      the radial approach were designed according to the activation sequence during
      sinus rhythm and the atrial coronary artery anatomy in normal dogs. The purpose
      of the present study was to determine whether the radial approach provides a more
      physiologic activation sequence and atrial transport function than the maze
      procedure. METHODS: Ten dogs that had undergone the radial approach (n = 5) or
      the maze procedure (n = 5) were studied 6 weeks postoperatively. Sinus node
      function and inducibility of atrial fibrillation were examined before and after
      operation. The atria were mapped endocardially with 212 electrodes, and atrial
      activation sequences during sinus rhythm and right atrial pacing were examined.
      Atrial transport function was assessed by transepicardial Doppler
      echocardiography. RESULTS: No dogs developed sinus node dysfunction
      postoperatively. Both the radial approach and the maze procedure equally
      prevented sustained atrial fibrillation. The atrial activation sequence was more
      synchronous after the radial approach than after the maze procedure. There was no
      electrically isolated region after the radial approach. The total activation time
      of the left atrium was significantly shorter after the radial approach than after
      the maze procedure (53.6+/-9.8 versus 70.5+/-9.6 ms, p<0.05). The ratio of peak
      flow velocity of the E wave to the A wave (peak E/A) of the transmitral Doppler
      flow was significantly smaller after the radial approach than after the maze
      procedure (1.7+/-0.4 versus 3.5+/-1.7, p<0.05). The atrial filling fraction of
      the transmitral Doppler flow was significantly larger after the radial approach
      than after the maze procedure (29.9%+/-7.3% versus 14.8%+/-5.0%, p<0.01). There
      was no significant difference in peak E/A and atrial filling fraction of the
      transtricuspid Doppler flow between the two procedures. CONCLUSIONS: The radial
      approach provides a more synchronous activation sequence and atrial transport
      function, and thus may represent a more physiologic alternative to the maze
      procedure as a surgical treatment for atrial fibrillation.

PMID- 10086524
TI  - First report of the Port Access International Registry.
AB  - BACKGROUND: For minimally invasive cardiac operations to be widely applicable,
      the risks must be equivalent to those of standard open-chest operations. This
      study analyzed the outcomes of patients recorded in the multicenter Port Access
      (PA) International Registry to establish operative risks. METHODS: Data were
      analyzed for intent to treat in 583 patients who underwent PA coronary artery
      bypass grafting (CABG), 184 who underwent PA mitral valve replacement, and 137
      who underwent PA mitral valve repair at 121 centers. RESULTS: Port Access was
      attempted in 1,063 patients and completed in 1,004 (94%). The operative mortality
      rate was 1% for PA CABG, 3.3% for PA mitral valve replacement, and 1.5% for PA
      mitral valve repair. Perioperative morbidity was low in all categories: stroke =
      1.1% to 3.6%, myocardial infarction = 0 to 1%, primary procedure reoperation = 0
      to 0.7%, renal failure = 0.2% to 0.7%, multiorgan failure = 0 to 0.5%, and atrial
      fibrillation = 5% to 7.3%. CONCLUSIONS: Data on 1,063 patients from 121 centers
      demonstrate that PA CABG and PA mitral valve operations can be performed safely,
      with morbidity and mortality rates similar to those associated with open-chest
      operations. Further studies are indicated to establish the long-term efficacy of
      this method and to analyze its effect on recovery time.

PMID- 10086525
TI  - Does a focal neurologic deficit contraindicate operation in a patient with
      endocarditis?
AB  - BACKGROUND: As many as 40% of patients with left-sided bacterial endocarditis
      will sustain a neurologic insult. The importance of a neurologic change as an
      indication or a contraindication for valve replacement remains controversial.
      METHODS: We performed a retrospective analysis of the records of 33 patients
      admitted to the University of Virginia Health Sciences Center between January 1,
      1978, and June 30, 1996, with a diagnosis of endocarditis and a neurologic
      change. RESULTS: All 33 patients had echocardiographic or pathologic evidence of
      left-sided endocarditis; 23 were seen with focal neurologic findings and had a
      mortality rate of 22% (5 of 23), and 10 patients were seen with nonfocal, diffuse
      encephalopathy and had a mortality rate of 60% (6 of 10) (p<0.05). Of the 33
      patients, 14 underwent operation and 19 were treated medically. The mortality
      rate was 21.4% (3 of 14) in the surgical group and 42.1% (8 of 19) in the medical
      group (p = not significant). In 71% (10 of 14) of the surgical patients, the
      operation was done within 1 week of the neurologic event. Additional neurologic
      deterioration occurred in 18.2% (2 of 11) of survivors in the surgical group and
      9.1% (1 of 11) in the medical group (p = not significant). CONCLUSIONS: Choosing
      therapy for a patient with endocarditis and a neurologic change remains a
      difficult challenge. Initial findings of nonfocal, global dysfunction on
      examination are a predictor of a poor outcome. By comparing surgical and medical
      groups derived from the same series of patients, it is clear that patients with
      bacterial endocarditis and central nervous system changes face substantial
      mortality regardless of intervention. However, these data demonstrate that when
      compared with a similar group of medical patients, surgical patients who require
      and receive operation early in the course of their illness do comparatively well.
      Improving outcomes by delaying surgical intervention may serve to "select out"
      hardier patients but will lead to the death of patients who might benefit from
      such intervention.

PMID- 10086526
TI  - Nitric oxide mediates neurologic injury after hypothermic circulatory arrest.
AB  - BACKGROUND: Prolonged hypothermic circulatory arrest (HCA) causes neurologic
      injury. However, the mechanism of this injury is unknown. We hypothesized that
      HCA causes nitric oxide production to result in neuronal necrosis. This study was
      undertaken to determine whether the neuronal nitric oxide synthase inhibitor
      17477AR reduces necrosis after HCA. METHODS: Thirty-two dogs underwent 2 hours of
      HCA at 18 degrees C. Nitric oxide synthase catalytic assay and intracerebral
      microdialysis for nitric oxide production were performed in acute nonsurvival
      experiments (n = 16). Sixteen animals survived for 72 hours after HCA: Group 1 (n
      = 9) was treated with 17477AR (Astra Arcus), and group 2 (n = 7) received vehicle
      only. Animals were scored from 0 (normal) to 500 (coma) for neurologic function
      and from 0 (normal) to 100 (severe) for neuronal necrosis. RESULTS:
      Administration of 17477AR reduced nitric oxide production in the striatum by 94%
      (HCA alone), 3.65+/-2.42 micromol/L; HCA and 17477AR, 0.20+/-0.14 micromol/L
      citrulline). Dogs treated with 17477AR after HCA had superior neurologic function
      (62.22+/-29.82 for group 1 versus 141.86+/-61.53 for group 2, p = 0.019) and
      significantly reduced neuronal necrosis (9.33+/-4.67 for group 1 versus 38.14+/
      2.23 for group 2, p<0.00001) compared with untreated HCA dogs. CONCLUSIONS: Our
      results provide evidence that neuronal nitric oxide synthase mediates neuronal
      necrosis after HCA and plays a significant role in HCA-induced neurotoxicity.
      Pharmacologic strategies to inhibit neuronal nitric oxide synthase after the
      ischemic period of HCA may be clinically beneficial.

PMID- 10086527
TI  - Predictive factors for mortality and cerebral complications in arteriosclerotic
      aneurysm of the aortic arch.
AB  - BACKGROUND: The incidence of cerebral complications is high in patients with
      aortic arch aneurysm. METHODS: Between December 1977 and December 1995, 246
      patients with arteriosclerotic arch aneurysm underwent operation. Thirty-nine
      patients had an aneurysm involving the entire arch, 193 had only distal arch
      aneurysm, and 14 had arch aneurysm extending to the descending aorta. Eighty
      seven patients underwent replacement of the total arch, 85 had replacement of
      only the distal arch, 14 had simultaneous replacement of the descending aorta, 45
      had patch repair, and 15 had thromboexclusion. Selective cerebral perfusion was
      used in 112 patients and partial bypass in 58 in the earlier series of patients,
      but deep hypothermic circulatory arrest with retrograde cerebral perfusion
      technique was exclusively applied in the most recent 76 patients. RESULTS: There
      were 50 (20%) early deaths and 37 (19%) late deaths. Postoperative stroke was
      found in 26 (11%) patients of which 13 (50%) died. Mutual predictive factors for
      postoperative mortality and stroke were earlier series, preoperative chronic
      renal failure, ruptured aneurysm, arch clamping during procedure, and using
      partial cardiopulmonary bypass. Among 129 patients operated on during the most
      recent 5 years, early mortality and incidence of stroke decreased to 14.7% and
      6.9%, respectively. CONCLUSIONS: Results of operations for arteriosclerotic
      aneurysms of the transverse aortic arch in 246 patients during a period of 17
      years have been improving but are still not satisfactory.

PMID- 10086528
TI  - Platelet aggregation during cardiopulmonary bypass evaluated by a laser light
      scattering method.
AB  - BACKGROUND: In regard to postoperative bleeding, the most important consequence
      of cardiopulmonary bypass (CPB) is the loss of aggregability. However, the
      mechanism of platelet aggregation loss during CPB is unclear. Newly developed
      particle-counting methods that use light scattering can be used to quantify
      changes in the number of platelet aggregates of different sizes after application
      of an aggregating stimulus. Using a light-scattering method, we investigated
      changes in platelet aggregation during cardiac operation. METHODS: Nineteen
      patients undergoing CPB were evaluated. Blood samples were obtained before the
      operation, 1 hour after initiation of CPB, at the end of CPB, at the end of the
      operation, and on day 1 after the operation. Platelet aggregation after
      stimulation by 2.5 micromol/L adenosine diphosphate and 2.0 microg/mL collagen
      was determined; small (9 to 25 microm), medium (25 to 50 microm), and large (50
      to 70 microm) aggregates were counted. RESULTS: Generation of medium and large
      aggregates after stimulation with adenosine diphosphate and collagen were
      significantly decreased with CPB, whereas, in spite of hemodilution, the quantity
      of the small aggregates was maintained at the elevated level. CONCLUSIONS: These
      results reflect the fact that CPB does not affect the first phase of aggregation.
      It suggests that platelet dysfunction associated with CPB is mainly caused by an
      inhibition in the development of small aggregates into larger aggregates.

PMID- 10086529
TI  - Favorable scanning electron microscopic findings of stapled saphenous vein
      carotid artery anastomoses.
AB  - BACKGROUND: In the progress toward "off-pump" endoscopic coronary artery surgical
      procedures, new techniques for coronary artery anastomoses are being developed.
      One such approach is the use of nonpenetrating titanium clips. We evaluated the
      quality of anastomoses achieved using this technique in a porcine model of
      saphenous vein-carotid artery grafting using scanning electron microscopy.
      METHODS: Bilateral saphenous vein-carotid artery interposition grafts were
      implanted in 10 "white race" pigs, using the nonpenetrating clips in one side of
      the neck and conventional hand suturing on the opposite side. One week after
      operation, the grafts were harvested. RESULTS: All grafts were patent 7 days
      after operation, and 40 anastomoses underwent scanning electron microscopic
      study. In all samples, the luminal surfaces of both the carotid artery and vein
      graft were covered by a continuous layer of endothelial cells up to the
      anastomosis. Anastomotic sites in all clipped samples and most of the sutured
      anastomoses were completely endothelialized, and anastomotic clefts were
      indistinguishable. However, in 25% of sutured specimens, the suture material
      remained clearly visible inside the lumen of the vessel, and the subendothelial
      matrix remained exposed, with extensive fibrin, red blood cells, and platelet
      deposition on its surface. CONCLUSIONS: Because the endothelial coverage
      consistently appeared to be complete and the subendothelial matrix was not
      exposed, it is likely that the risk of early anastomotic thrombosis is reduced by
      using the nonpenetrating titanium clips.

PMID- 10086530
TI  - Intravalvular implantation technique for aortic valve replacement in aortitis
      syndrome.
AB  - BACKGROUND: Paravalvular leakage is one of the most serious complications of
      aortic valve replacement in patients with aortitis syndrome. The purpose of this
      study was to compare the effectiveness of the intravalvular implantation
      technique in preventing paravalvular leakage with that of the conventional
      technique. METHODS: Since 1982, 14 patients with aortic regurgitation caused by
      aortitis syndrome have undergone aortic valve replacement at our institute. An
      intravalvular implantation technique was applied in 7 of the 14 patients. The
      technique consists of suturing a prosthetic valve to the aortic annulus and
      sandwiching the leaflets between exogenous felt pledgets and the inflamed aortic
      annulus. RESULTS: Paravalvular leakage occurred in 3 of 7 patients in the
      conventionally treated group and in none of 7 in the intravalvular implantation
      group. CONCLUSIONS: The intravalvular implantation technique is effective in
      preventing paravalvular leakage in patients with aortitis syndrome.

PMID- 10086531
TI  - Cardiac reoperations in octogenarians: analysis of outcomes.
AB  - BACKGROUND: With the rapid growth of the elderly segment of the population, more
      octogenarians are referred for complex cardiac interventions, including
      reoperations. Data regarding the outcomes, quality of life, and long-term results
      after reoperative open-heart surgical procedures in octogenarians are scarce.
      METHODS: We retrospectively studied 113 consecutive octogenarians (mean age, 83+/
      2.6 years) who underwent reoperative cardiac procedures within a 13-year period.
      Coronary artery bypass grafting (CABG) was performed in 49 patients (CABG group),
      valvular procedures (aortic, mitral, or tricuspid valve, alone or in combination)
      in 35 (valve group), and combined CABG and valve intervention in 29 (combined
      CABG and valve group). RESULTS: The 30-day mortality rate was 8% (4 of 49) for
      the CABG group, 9% (3 of 35) for the valve group, and 17% (5 of 29) for the
      combined CABG and valve group. One- and 5-year actuarial survival rates were,
      respectively, 85%+/-5% and 58%+/-10% for the CABG group, 78%+/-7% and 53%+/-12%
      for the valve group, and 69%+/-9% and 63%+/-10% for the combined CABG and valve
      group. Sixty-one percent of patients in the CABG group, 40% in the valve group,
      and 38% in the combined CABG and valve group were in New York Heart Association
      class I or II postoperatively at a mean follow-up time of 2.1+/-2.4 years.
      Similarly, 91%, 85%, and 80%, respectively, thought that they had an improved
      quality of life and were satisfied with their functional status. CONCLUSIONS:
      Cardiac reoperations can be performed successfully in most octogenarians,
      although with an increased risk, particularly in the combined CABG and valve
      group. Long-term survival is acceptable with improved quality of life and
      functional status. However, it is possible that these results could be improved
      in this high-risk group of patients with earlier referral and surgical
      intervention, for the effective use of health care resources.

PMID- 10086532
TI  - Beating heart coronary surgery supported by an axial blood flow pump.
AB  - BACKGROUND: We have previously presented a method for performing coronary artery
      bypass graft operation on the beating heart without cardiopulmonary bypass (CPB).
      This method has now been explored. METHOD: Thirty-two patients were prospectively
      randomized. The study group was operated on using an axial blood flow pump
      (Hemopump; HP) as circulatory support. Operations were performed on the beating
      heart. The control group was operated on using CPB, aortic cross-clamping, and
      cardioplegic arrest. RESULTS: All patients went through the procedure without
      major complications, and were discharged from the hospital. No statistical
      differences were observed between the groups for time on support (HP, 60.5
      minutes; CPB, 70.5 minutes) or total operating time (HP, 178 minutes; CPB, 162
      minutes). The number of grafts was greater in the CPB group (HP, 1.8; range, 1 to
      3; CPB, 2.5; range, 1 to 4; p = 0.03). Statistical differences were found for
      intraoperative bleeding (HP mean, 312 mL; CPB mean, 582 mL; p = 0.0003) and
      myocardial trauma as measured by postoperative troponin-T values (HP, 0.23
      microg/L; CPB, 1.17 microg/L; p = 0.004). CONCLUSIONS: Hemopump-supported
      coronary artery bypass graft operation has been shown to be a safe and feasible
      procedure with the potential benefits of reduced operative bleeding and
      myocardial damage without prolonging intraoperative support or total operating
      time.

PMID- 10086533
TI  - Evaluation of a compressive-type skeletal muscle pump for cardiac assistance.
AB  - BACKGROUND: Recent investigations have focused on using the latissimus dorsi
      muscle for cardiac assistance. Although cardiomyoplasty has been applied
      clinically, other procedures remain experimental, but promising, modes of cardiac
      assistance. We assessed the latissimus dorsi muscle as an in situ energy source
      for circulatory assist devices. METHODS: We developed a pneumatic chamber as a
      compressive-type muscle actuator. The chamber was implanted under the latissimus
      dorsi muscle and converted contractile power into pneumatic pressure. The effect
      of chamber position and size and the influence on muscle blood flow were
      examined. After muscle conditioning, the pump performance of a circulatory assist
      device driven by the chamber was evaluated. RESULTS: The chamber functioned
      better when placed in the proximal position of the latissimus dorsi muscle. The
      size affected the generated pneumatic pressure, and the higher resting pressure
      of the chamber reduced the muscle blood flow. The maximum stroke work of the
      circulatory assist device was greater than that of the right ventricle but less
      than that of the left ventricle. The chamber could drive the circulatory assist
      device against the systemic range of afterload in which a high preload was
      available. Long-term adhesion surrounding the chamber reduced the pressure
      generation capability. CONCLUSIONS: The compressive-type muscle actuator using
      the latissimus dorsi muscle generated acceptable hemodynamic work for right
      ventricular bypass or aortic counterpulsation.

PMID- 10086534
TI  - Effect of sialyl Lewis(x) oligosaccharide on myocardial and cerebral injury in
      the pig.
AB  - BACKGROUND: Although administration of the sialyl Lewis(x) oligosaccharide may
      reduce myocardial injury after ischemia-reperfusion, its effect on coronary and
      cerebral microvascular regulation and its clinical application during cardiac
      operation have not been examined. METHODS: Pigs were placed on normothermic
      cardiopulmonary bypass after 30 minutes of left anterior descending coronary
      artery occlusion. The hearts were then arrested with cold high potassium
      cardioplegia. After 1 hour the cross-clamp was removed and the pigs were weaned
      from cardiopulmonary bypass and perfused for an additional 1 hour. CY-1503 (a
      sodium salt of the sialyl Lewis(x) oligosaccharide, n = 6) was administered
      before reperfusion. Six other pigs received saline vehicle. Endothelium-dependent
      relaxation of precontracted coronary and brain arterioles (70 to 180 microm) to
      adenosine 5'-diphosphate and endothelium-independent relaxation to sodium
      nitroprusside were studied in vitro with videomicroscopy. Control values were
      obtained from uninstrumented pigs. Myeloperoxidase activity in the myocardium and
      brain was measured to quantify neutrophil infiltration. Cardiac function and
      perfusion were assessed by left ventricular systolic pressure, maximum rate of
      increase of left ventricular pressure, left anterior descending coronary artery
      blood flow and percent segmental shortening, and cerebral vascular resistance,
      internal carotid artery blood flow, and the constitutively expressed and
      inducible isoform of nitric oxide synthase mRNA were measured. RESULTS: The
      impaired myocardial contractile function after ischemia and cardioplegia was not
      improved by administration of CY-1503. The reduced endothelium-dependent
      relaxation responses of coronary and brain arterioles during ischemia followed by
      cardioplegia and cardiopulmonary bypass were improved with CY-1503, but the
      altered pattern of organ perfusion was not improved. Myeloperoxidase activity was
      increased in the heart after ischemia-cardioplegia and in the brain after
      cardiopulmonary bypass. CY-1503 reduced myeloperoxidase activity in both the
      myocardium and in the brain. Expressions of myocardial inducible isoform or
      constitutively expressed nitric oxide synthase were not altered in the heart.
      CONCLUSIONS: Although the sialyl Lewis(x) oligosaccharide does reduce neutrophil
      infiltration and endothelial injury in the coronary and cerebral microcirculation
      after cardiopulmonary bypass, it does not have significant beneficial acute
      effects on organ perfusion or function in the myocardium or brain.

PMID- 10086535
TI  - Temporary luminal arteriotomy seal: III. Postmortem arteriosclerotic human
      coronary artery.
AB  - BACKGROUND: Recently, we described a temporary luminal arteriotomy seal that
      provided a bloodless arteriotomy without obstructing recipient artery blood flow
      during bypass grafting in nonarteriosclerotic porcine arteries. This postmortem
      study assessed the sealing properties in irregular arteriosclerotic human
      coronary arteries. METHODS: Three hearts were obtained from donated corpses
      within 24 hours of death. The coronary arteries were pressure-perfused at 60 mm
      Hg with citrated porcine blood. At 15 anastomosis sites in four different
      coronary arteries, an end-to-side anastomosis was created using a 200-microm
      thick polyurethane seal. Adequacy of sealing was determined at perfusion
      pressures of 60, 40, and 20 mm Hg. RESULTS: After insertion, the arteriotomy was
      sealed instantaneously in 10 of 15 anastomoses. After repositioning, complete
      sealing with a bloodless operative field was obtained in all cases. Low
      intracoronary transmural pressure did not impede sealing. In 8 of 15 anastomoses,
      minor leakage without obscuring the arteriotomy edges was observed during
      anastomotic suturing. Histologic examination revealed no intimal tear or
      dissection caused by the anastomotic procedure. CONCLUSIONS: In postmortem
      obtained arteriosclerotic human coronary arteries, the temporary luminal
      arteriotomy seal provided optimal visualization of the coronary anastomosis site
      in combination with persistent distal perfusion.

PMID- 10086536
TI  - Intracardiac transplantation of skeletal myoblasts yields two populations of
      striated cells in situ.
AB  - BACKGROUND: Adult heart lacks stem cells and cannot effectively regenerate. In
      contrast, skeletal muscle is constantly undergoing repair. We proposed to
      transplant immature skeletal myoblasts into injured myocardium. METHODS:
      Approximately 7x10(6) soleus skeletal myoblasts were expanded in vitro from adult
      New Zealand White rabbits (n = 23) whose posterior left ventricle was cryoinjured
      to create a transmural lesion. Autologous myoblasts (n = 18) or saline (n = 5)
      was transplanted into the central cryolesion at the time of injury (n = 6) or 1
      week later (n = 12). Hearts were harvested 2 weeks after injection. RESULTS:
      Myoblast transfer did not incur further morbidity. After cryolesion, grossly, a
      1.6-cm epicardial hemorrhagic lesion could be seen. Histologically, the
      transmural lesion contained inflammatory cells and active scarring but no viable
      cardiomyocytes. Electron microscopy demonstrated a predominance of collagen and
      fibroblasts. Nine hearts contained multinucleated cells within the cryolesion
      that covered approximately 75% of the central cryolesion in 17% of animals.
      Immunohistochemical analysis confirmed their skeletal muscle origin. At the
      periphery of the lesion, isolated clusters of nonskeletal muscle cells could be
      visualized (n = 12) that resembled immature cardiocytes. CONCLUSIONS: Autologous
      skeletal myoblasts can regenerate viable striated tissue within damaged
      myocardium. Myoblast transfer warrants further investigation as a new method for
      improving myocardial performance within infarcted myocardium.

PMID- 10086537
TI  - Progression of steroid-associated osteoporosis after heart transplantation.
AB  - BACKGROUND: Osteoporosis has been recognized as an important side effect of long
      term and of pulsed steroid application after heart transplantation. METHODS: In
      June 1989 a prospective clinical trial was started to study bone demineralization
      by quantitative computed tomographic scan. All patients received vitamin D and
      calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council
      Standard Units subcutaneously per day was administered in 14-day cycles, whereas
      group II patients (n = 31) received a placebo preparation. Repeat trabecular and
      cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar
      spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation.
      RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density
      decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart
      transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months
      in the calcitonin group. The values for cortical bone density decreased
      significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart
      transplantation. Comparable results were obtained in the placebo group. In both
      groups bone density remained stable thereafter. Intergroup differences were not
      of statistical significance. CONCLUSIONS: In heart transplant recipients
      progressive trabecular bone demineralization is limited to the first 3
      postoperative months. Thereafter, bone density remained stable. A positive effect
      of synthetic calcitonin in addition to prophylactic calcium and vitamin D
      application could not be proved by repeat quantitative computed tomography.

PMID- 10086538
TI  - Enhanced preoperative C-reactive protein plasma levels as a risk factor for
      postoperative infections after cardiac surgery.
AB  - BACKGROUND: We examined the possible predictive role of preoperative C-reactive
      protein (CRP) levels for postoperative infections in patients who have cardiac
      operations. METHODS: CRP levels were determined on the day before the operation
      and on postoperative days 1 to 4 and 6 in 593 consecutive patients. Furthermore,
      we documented infectious disease-related data. RESULTS: Patients in whom an
      infection developed during the postoperative course (n = 87) had significantly
      higher CRP levels on the day before operation (17.8+/-3.9 mg/L compared with
      7.7+/-0.7 mg/L; p<0.001) and on postoperative days 4 and 6. The incidence of
      postoperative infections was significantly higher in patients with increased
      preoperative CRP levels than in those with normal preoperative CRP levels (25.3%
      versus 11.2%, respectively; p<0.001). Furthermore, patients with higher
      preoperative CRP levels had a significantly longer postoperative hospital stay
      than those with normal preoperative CRP levels (10.8+/-1.2 days versus 7.8+/-0.3
      days; p<0.001). Multivariate analysis, including classic risk factors and
      increased preoperative CRP levels, demonstrated that higher preoperative CRP was
      the most important variable predicting postoperative infection (odds ratio = 2.7;
      95% confidence interval = 1.7 to 4.3; p<0.001). CONCLUSIONS: Patients with higher
      preoperative CRP levels are at increased risk for postoperative infections.
      Therefore, preoperative measurement of CRP might be a useful, predictive marker
      in risk stratification for postoperative infections in patients scheduled for
      cardiac operations.

PMID- 10086539
TI  - Early changes in the time course of myocardial contraction after correcting
      aortic regurgitation.
AB  - BACKGROUND: Correcting aortic regurgitation causes significant changes in left
      ventricular loading conditions, but few observations have been made
      intraoperatively of early effects on myocardial function. METHODS: We studied 18
      patients (mean age, 59+/-12 years; 14 men) in whom aortic regurgitation was
      corrected with a stentless biologic valve. Overall left ventricular function was
      studied by thermodilution cardiac output, ventricular filling pressure, and
      systemic arterial pressure. Regional myocardial function was assessed from
      intraoperative transesophageal M-mode echocardiography and high fidelity
      ventricular pressure recordings before cardiopulmonary bypass, and 0.5, 1, 3, 6,
      12, and 20 hours after operation. Time course of contraction, and magnitude of
      left ventricular systolic wall stress, dimensional shortening, myocardial power,
      and stroke work were measured. RESULTS: Global hemodynamics: there was an
      immediate decrease in left ventricular stroke volume (58+/-31 mL versus 80+/-30
      mL, p = 0.004) and stroke work index (250+/-86 mJ/m versus 401+/-198 mJ/m, p =
      0.005), but systemic arterial pressure (79+/-11 mm Hg versus 65+/-10 mm Hg, p =
      0.002), increased at constant heart rate and end-diastolic pressure. Regional
      myocardial function and timing: peak systolic wall stress, dimensional shortening
      rate, and myocardial power production were all unchanged with operation. However,
      myocardial stroke work decreased (3.0+/-1.3 mJ/cm versus 4.8+/-2.4 mJ/cm, p =
      0.009), attributable to shortening of the duration of systole (475+/-91 ms versus
      543+/-67 ms, p<0.001). Diastolic time increased from 34%+/-18% to 71%+/-33% of
      systolic pulse duration (p<0.001). CONCLUSIONS: Correcting aortic regurgitation
      causes an early decrease in regional and global stroke work and increases
      diastolic time, although systolic wall stress does not decrease immediately.
      These beneficial effects are achieved by reducing the duration rather than
      altering the peak intensity (power) of myocardial contraction.

PMID- 10086540
TI  - Use of transesophageal echocardiography for postoperative evaluation of right
      ventricular function.
AB  - BACKGROUND: No method has been available to assess the right ventricular (RV)
      pressure-volume relation in the operating room or intensive care unit. Left
      ventricular cross-sectional area measured by echocardiography using the
      technology of automated border detection has been used to construct left
      ventricular pressure-area (P-A) loops. In the human right ventricle, however,
      this approach has not been validated. METHODS: We recorded RV P-A loops in 14
      patients in the intensive care unit using transesophageal echocardiography.
      Multiple RV P-A loops were obtained by reducing preload with intravenous
      nitroglycerin, thereby elucidating the end-systolic P-A relation. RESULTS: With
      an incremental dose of dobutamine, the slope of the RV end-systolic P-A relation
      increased (from 4.56+/-2.42 to 7.34+/-3.62 mm Hg/cm2, p<0.01), with no change in
      the x-axis intercept, which implied increased contractility. Furthermore, in the
      operating room we validated the use of RV cross-sectional area as a surrogate for
      RV volume by demonstrating the close correlation between the stroke area (maximal
      RV area minus minimal RV area) and stroke volume (r = 0.962; p<0.0001).
      CONCLUSIONS: Transesophageal echocardiography with automated border detection is
      a promising tool for elucidating RV function through the analysis of RV P-A
      loops.

PMID- 10086541
TI  - Scimitar syndrome presenting in infancy.
AB  - BACKGROUND: Scimitar syndrome has a variable presentation based on the age at
      which the diagnosis is made. In general, infants presenting in heart failure have
      a greater number of associated anomalies and their prognosis is much worse.
      METHODS: We reviewed the records of all patients under our care at St. Louis
      Children's Hospital who presented with symptoms attributable to scimitar syndrome
      during their infancy. Twelve patients were identified. The average age at
      presentation was 6 weeks. RESULTS: The most common symptom at presentation was
      tachypnea. The chest roentgenogram demonstrated dextroposition of the heart and
      hypoplastic right lung. Only 1 patient had the classic "scimitar sign." Cardiac
      catheterization demonstrated pulmonary hypertension (pulmonary artery systolic
      pressure, 73.9+/-21.8 mm Hg). The Qp:Qs was 3.1+/-1.5:1. Two patients with severe
      associated anomalies were treated medically and both died. Two patients underwent
      occlusion of the systemic collaterals; one died and the other ultimately
      underwent complete repair due to persistence of the symptoms of heart failure.
      Two patients had primary right pneumonectomy and both are alive and well. Seven
      patients underwent complete repair (one after coil occlusion of the systemic
      arterial collaterals) and one died; three subsequently developed occlusion of the
      baffle from the orifice of the anomalous pulmonary vein and required
      pneumonectomy. Two patients required lung transplantation due to persistent
      pulmonary hypertension in one and recurrent bilateral pulmonary venous stenosis
      in the other. CONCLUSIONS: Infants presenting with scimitar syndrome generally
      have symptoms of tachypnea and chest roentgenograms showing dextrocardia and
      hypoplastic right lung. Although repair of the anomalous venous return and
      ligation of collaterals is generally recommended, right pneumonectomy (either as
      primary therapy or if repair failed) had similar early and late results.

PMID- 10086542
TI  - Phenoxybenzamine improves systemic oxygen delivery after the Norwood procedure.
AB  - BACKGROUND: Achieving adequate systemic oxygen delivery after the Norwood
      procedure frequently is complicated by excessive pulmonary blood flow at the
      expense of systemic blood. We hypothesized that phenoxybenzamine could achieve a
      balanced circulation through reduction of systemic vascular resistance. METHODS:
      In this prospective, nonrandomized study, oximetric catheters were placed in the
      superior vena cava for continuous monitoring of systemic venous oxygen
      saturation. Postoperative hemodynamic variables were compared between 7 control
      patients and 8 patients who received phenoxybenzamine. RESULTS: The hospital
      survival rate was 93% (14 of 15 patients). Improvements in postoperative
      hemodynamics in the phenoxybenzamine group included a higher systemic venous
      oxygen saturation, a narrower arteriovenous oxygen content difference, a lower
      ratio of pulmonary to systemic flow, and a lower indexed systemic vascular
      resistance. In the phenoxybenzamine group, mean arterial blood pressure was
      related directly to systemic oxygen delivery, in contrast to the control group,
      where mean arterial pressure was related directly to indexed systemic vascular
      resistance and the ratio of pulmonary to systemic circulation. CONCLUSIONS:
      Continuous postoperative monitoring of systemic venous oxygen saturation in a
      patient who has undergone the Norwood procedure provides early identification of
      low systemic oxygen delivery and an elevated ratio of pulmonary to systemic
      circulation. In this pilot study, phenoxybenzamine appeared to improve systemic
      oxygen delivery during the early postoperative period after the Norwood
      procedure. Further studies are indicated to confirm these results.

PMID- 10086543
TI  - Left ventricular assist device improves survival in children with left
      ventricular dysfunction after repair of anomalous origin of the left coronary
      artery from the pulmonary artery.
AB  - BACKGROUND: Repair of anomalous origin of the left coronary artery from the
      pulmonary artery (ALCAPA) in infants carries a high operative risk, particularly
      in infants with myocardial infarction and poor left ventricular function. The
      marked recovery of left ventricular function reported late after repair, however,
      suggests that an aggressive approach to repair should be undertaken. METHODS: Of
      31 children undergoing primary repair of ALCAPA at our institution from 1987 to
      1996, 26 were infants (6 weeks to 9 months old). All but 2 had severe left
      ventricular dysfunction, and 8 had moderate to severe mitral regurgitation. Seven
      children were unable to be weaned from cardiopulmonary bypass because of poor
      left ventricular function and elevated left atrial pressure. These 7 children
      were placed on mechanical left ventricular support using a centrifugal pump, with
      support ranging from 2.2 to 70.6 hours. RESULTS: One child died shortly after the
      start of left ventricular assist (2.2 hours), and another died of arrhythmia
      within 24 hours after successful decannulation. All 5 survivors had significant
      improvement in left ventricular function, with 2 requiring late mitral valve
      repair. CONCLUSIONS: Infants with ALCAPA who have severe left ventricular
      dysfunction represent a higher risk group for repair. However, with use of
      mechanical circulatory support in those unable to be weaned from cardiopulmonary
      bypass, a high survival rate can be achieved with good long-term recovery. We
      conclude that an aggressive approach to early repair in all children with ALCAPA
      is warranted, regardless of the degree of left ventricular dysfunction.

PMID- 10086544
TI  - Reduced inotropic support after aprotinin therapy during pediatric cardiac
      operations.
AB  - BACKGROUND: Several reports indicate that aprotinin treatment before and during
      cardiopulmonary bypass (CPB) might have a protective effect on the myocardium. We
      evaluated the hemodynamic effects of perioperative aprotinin treatment. METHODS:
      We conducted a randomized, double-blind, placebo-controlled trial in 34 infants
      (mean age, 2.5 years) who had cardiac operations. Half of the patients received
      high-dose aprotinin therapy. There were no significant differences between the
      aprotinin and placebo groups with respect to age, weight, sex, aortic cross-clamp
      time, and CPB time. The following data were recorded at arrival in the intensive
      care unit 6, 12, 24, and 48 hours after termination of CPB: heart rate, blood
      pressure, left atrial pressure, central-peripheral temperature difference,
      arterial-central venous oxygen saturation difference, urine output, serum
      creatinine, lactate and neutrophil elastase levels, the Doppler echocardiographic
      factors shortening fraction and preejection period/left-ventricular ejection
      time, and cumulative doses of catecholamines (epinephrine), enoximone, and
      furosemide. RESULTS: No hemodynamic variable showed any significant difference
      between aprotinin and placebo groups. Urine output, creatinine, lactate, and
      elastase levels, as well as the cumulative doses of furosemide and epinephrine
      were not significantly different. Twelve hours after CPB 10 patients in the
      placebo group and 4 in the aprotinin group had received enoximone (p<0.05). The
      placebo group had received significantly larger doses of enoximone than the
      aprotinin group at arrival in the intensive care unit (0.13+/-0.05 versus 0
      mg/kg), 12 hours after CPB (0.58+/-0.14 versus 0.18+/-0.09 mg/kg), 24 hours after
      CPB (1.11+/-0.24 versus 0.42+/-0.16 mg/kg), and 48 hours after CPB (1.61+/-0.40
      versus 0.86+/-0.28). At 6 hours the difference did not reach statistical
      significance. CONCLUSIONS: Clinical and hemodynamic status of the aprotinin
      treated patients was similar to that of the placebo-treated patients in the first
      48 hours after CPB. The placebo group, however, required significantly more
      inotropic support by enoximone than the aprotinin group to achieve this goal.

PMID- 10086545
TI  - Does left ventricular outflow tract obstruction influence outcome of interrupted
      aortic arch repair?
AB  - BACKGROUND: In previous studies left ventricular outflow tract obstruction
      (LVOTO) has been recognized as an important factor affecting survival and
      reoperation probability in patients having repair of an interrupted aortic arch
      (IAA). METHODS: All 72 patients who underwent operation for IAA from January 1,
      1985 to June 30, 1997 were reviewed. The presence or absence of LVOTO was noted
      and the immediate and long-term results were analyzed. RESULTS: Type A IAA was
      found in 23 patients and type B IAA in 49 patients. Anomalous right subclavian
      artery was noted in 15 patients, all of whom had type B IAA. LVOTO was identified
      in 36 patients before arch repair and was associated with the presence of type B
      IAA and anomalous right subclavian artery (p = 0.02 and 0.007, respectively).
      There were 2 hospital deaths (within 30 days) for a mortality of 2.8% (confidence
      limit [CL] = 0% to 6.6%). There were 7 late deaths over 3,737 patient-months of
      follow-up (9.7%, CL = 2.9% to 16.6%). Actuarial survival for the whole cohort was
      84.8% (CL = 73.2% to 94.4%) at 12 years. There was 87% 10-year survival (CL = 60%
      to 93%) for patients with LVOTO at presentation compared with 83% (CL = 62% to
      92%) for patients without LVOTO (p = 0.85, hazard function 0.87). Twenty-eight
      patients have required at least one reoperation. The use of conduits to restore
      right ventricular to pulmonary artery continuity predicted the need for
      reoperation (p = 0.0001). Patients with presence of a nonseptatable heart were
      also more likely to need reoperation (p = 0.027) when compared to the rest of the
      cohort. Freedom from reoperation was 47.3% (CL = 30% to 62%) at 12 years. In
      patients with LVOTO, freedom from reoperation (55% at 10 years, CL = 33% to 72%)
      was not significantly different from those patients without LVOTO at presentation
      (29% at 10 years, CL = 7% to 56%; p = 0.97, hazard function 0.7). Actuarial
      freedom from recurrent arch obstruction requiring reintervention was 82.7% (CL =
      66.7% to 98.7%) at 12 years. CONCLUSIONS: Neonatal complete repair of patients
      with IAA is possible with low mortality. LVOTO was not a significant risk factor
      for hospital or late death in patients having complete repair of IAA during this
      period. The use of conduits for right ventricular to pulmonary artery continuity
      and the presence of a nonseptatable heart are important risk factors for further
      operation and will continue to provide added morbidity to these patients.

PMID- 10086546
TI  - Propranolol for the prevention of postoperative arrhythmias in general thoracic
      surgery.
AB  - BACKGROUND: Prevention of postoperative arrhythmias in patients undergoing
      general thoracic surgery is desirable to prevent morbidity. METHODS: A
      randomized, double-blind, placebo controlled trial of propranolol (10 mg every 6
      hours) for 5 days was undertaken in patients undergoing major thoracic operations
      to determine whether arrhythmias requiring treatment could be reduced. Secondary
      outcomes included overall arrhythmia rate, adverse events, and length of stay.
      Arrhythmias were assessed by 72-hour Holter monitoring. Patients with a history
      of heart failure, asthma, advanced heart block, preexisting arrhythmias,
      sensitivity to propranolol, or use of antiarrhythmic drugs were excluded.
      RESULTS: Using the intention-to-treat principle there was a 70% relative risk
      reduction from 20% to 6% in the rate of treated arrhythmias with propranolol (p =
      0.071, 95% confidence interval 0.6% to 27.2%). Overall arrhythmias were common
      but usually benign. Adverse effects were common, although generally mild with
      hypotension and bradycardia being reported more often in the propranolol group.
      Length of stay was not different. CONCLUSIONS: There was a trend to a reduction
      in the risk of perioperative arrhythmias with propranolol. Moreover, propranolol
      was well tolerated showing a slight increase in minor adverse events.

PMID- 10086547
TI  - Induction immunosuppression for lung transplantation with OKT3.
AB  - BACKGROUND: The use of OKT3, an anti-CD3 monoclonal antibody, for
      immunosuppressive therapy for lung transplantation has been restricted because of
      concerns regarding infectious risk and cardiopulmonary instability after its
      administration. METHODS: Fifty-two patients received OKT3 (5 mg/d intravenously
      for 10 days) for induction of immunosuppressive therapy, along with azathioprine
      (1.5 mg x kg(-1) x d(-1) intravenously) and enteral cyclosporine (12 mg x kg(-1)
      x d(-1)). Maintenance steroid therapy was begun on postoperative day 8.
      Prophylactic antifungal therapy (fluconazole or amphotericin B) and ganciclovir
      was used in all patients. Serial transbronchial biopsy and measurements of
      pulmonary function were used to assess patients for evidence of infection or
      rejection. Cytomegalovirus infection was diagnosed by biopsy or the presence of
      cytomegalovirus antigenemia. RESULTS: The 30-day mortality rate was 4%; the in
      hospital mortality rate was 8%. Acute graft failure was seen in 6 patients. The
      median length of intubation was 5 days, and the median hospital stay was 30 days.
      Systemic and pulmonary artery systolic pressures, cardiac index, and ratio of
      arterial partial oxygen pressure to fraction of inspired oxygen showed no
      significant alteration after OKT3 dosage. Gram-negative pulmonary infections were
      identified in 12 patients. Aspergillus infection was seen in 7 patients.
      Cytomegalovirus infection in 8 patients responded to ganciclovir and did not
      affect mortality. Respiratory syncytial viral infection was seen in 7 patients.
      Acute rejection was never seen during OKT3 administration. No episodes of acute
      rejection were identified in 14 patients at any time postoperatively. In the
      remainder, episodes of acute rejection responded to steroid or antithymocyte
      globulin therapy. At a median length of follow-up of 31 months, freedom from
      obliterative bronchiolitis was 69%+/-9% at 36 months. The overall survival rate
      was 88%+/-5% at 12 months, 82%+/-6% at 24 months, and 74%+/-7% at 36 months after
      transplantation. CONCLUSIONS: OKT3 is a safe and effective agent for induction
      immunosuppressive therapy in lung transplant recipients that limits the incidence
      of acute rejection and may decrease the incidence of obliterative bronchiolitis.

PMID- 10086548
TI  - Reduced ischemia-reperfusion injury with rolipram in rat cadaver lung donors:
      effect of cyclic adenosine monophosphate.
AB  - BACKGROUND: The perfusion of rat lungs retrieved from cadavers with a solution
      containing isoproterenol has been shown to ameliorate the ischemia-reperfusion
      injury seen in lungs retrieved after death, and this protective effect parallels
      increases in tissue cyclic adenosine monophosphate levels. In this study, we
      investigated the effect of rolipram, a phosphodiesterase inhibitor, on capillary
      permeability and lung cyclic adenosine monophosphate levels in lungs retrieved
      from circulation-arrested rats. METHODS: Using an isolated perfused lung circuit,
      we retrieved lungs from circulation-arrested donor rats either ventilated with
      100% oxygen or not ventilated for varying postmortem times. The lungs were
      reperfused with or without rolipram (2 micromol/L). The capillary filtration
      coefficient and wet to dry weight ratio, indicators of pulmonary vascular
      integrity, were determined, and tissue levels of adenine nucleotides and cyclic
      adenosine monophosphate were measured by high-performance liquid chromatography.
      RESULTS: The capillary filtration coefficient was significantly reduced in
      nonventilated cadaver lungs reperfused with rolipram 120 minutes after death
      (p<0.05). Oxygen ventilation or reperfusion with rolipram had a similar effect on
      the capillary filtration coefficient. Cyclic adenosine monophosphate levels were
      significantly higher in rolipram-reperfused lungs retrieved 120 minutes after
      death in both oxygen-ventilated (p<0.01) and nonventilated (p<0.01) lungs.
      CONCLUSIONS: In lungs from nonventilated, circulation-arrested donors,
      reperfusion with rolipram reduces the ischemia-reperfusion injury that may be due
      to intracellular cyclic adenosine monophosphate. Alteration of perfusate may have
      an impact on capillary leak caused by antecedent ischemia. Thus, rolipram may be
      a useful adjunct in the preservation of donor lungs retrieved after death.

PMID- 10086549
TI  - Pulmonary dirofilariasis.
AB  - BACKGROUND: Pulmonary dirofilariasis is a rare entity caused by Dirofilaria
      immitis, the dog heartworm that is transmitted to humans by mosquitos. This
      filarial nematode enters the subcutaneous tissue, travels to the right ventricle
      where it dies, and then embolizes the pulmonary vasculature, causing a small
      pulmonary infarction, which subsequently appears as a solitary nodule. Although
      these nodules are usually identified incidentally by chest radiography in
      asymptomatic patients, the lesion is generally presumed to be neoplastic.
      Diagnosis is made by surgical excision. METHODS: We reviewed the pathology
      reports at Memorial Medical Center, Savannah, GA since 1990. RESULTS: There have
      been approximately 150 cases reported in the literature worldwide. We found 4
      patients with pulmonary dirofilariasis diagnosed at our hospital since 1992. A
      review of the pathogenesis of the disease and clinical manifestations, diagnosis,
      and treatment of this entity are presented. CONCLUSIONS: Pulmonary dirofilariasis
      is a benign condition, transmitted by mosquitos to humans that results in
      peripheral pulmonary nodules. Awareness of this entity is important in the
      differential diagnosis of pulmonary coin lesions.

PMID- 10086550
TI  - University of Wisconsin solution with butanedione monoxime and calcium improves
      rat lung preservation.
AB  - BACKGROUND: A limitation to fully using lung transplantation for patients with
      end-stage lung diseases is short, safe preservation time (4 to 6 hours). Our goal
      is to extend this to 24 hours or more, which would greatly improve clinical lung
      transplantation. METHODS: We used the isolated perfused rat lung to test how two
      preservation solutions (low potassium dextran and University of Wisconsin
      solution) affected quality of lungs after 6, 12, and 24 hours of preservation.
      Also, we tested modifications of the University of Wisconsin solution, including
      reversing the ratio of Na/K, the addition of 1.5 mmol/L calcium, and the
      combination of calcium and butanedione monoxime, agents that improve cardiac
      preservation. After preservation at 4 degrees C, lungs were reperfused at 37
      degrees C with a physiologically balanced solution. Pulmonary artery flow rate,
      airway peak inspiratory pressure, and tissue edema were used to assess degree of
      preservation and reperfusion injury. RESULTS: Low potassium dextran solution gave
      poor preservation (decreased pulmonary artery flow, tissue edema) after 12 hours
      of cold storage. There were no differences between regular and reversed Na/K
      ratio University of Wisconsin solutions at 12 or 24 hours of preservation.
      Addition of calcium had no beneficial effect on lung preservation. However,
      University of Wisconsin solution with calcium and butanedione monoxime gave
      excellent 24-hour cold storage, with pulmonary artery flow rate, tissue edema,
      and airway peak inspiratory pressure equal to control (0 hours of preservation)
      lungs. CONCLUSIONS: The University of Wisconsin solution appears capable of lung
      preservation for up to 24 hours if modified to contain calcium and butanedione
      monoxime. The mechanism of action of butanedione monoxime may be related to the
      suppression of smooth muscle contraction resulting in vasodilation of the cold
      stored lung on reperfusion.

PMID- 10086551
TI  - Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15
      patients.
AB  - BACKGROUND: Thymic neuroendocrine tumor (carcinoid tumor) is rare, and prognosis
      for patients with this tumor has been difficult to predict. METHODS: The medical
      records of 15 patients were reviewed, and the patients were classified according
      to tentative TNM classification and histologic grade. RESULTS: Ten (66.7%) of 15
      patients were male. Lymph node metastases were identified in 9 (60%) of 15
      patients at the time of resection. There were one grade 1, nine grade 2, and five
      grade 3 tumors. Total resection was possible in 13 patients. Distant metastases
      developed in 10 (76.9%) of these 13 patients, although no local recurrence
      developed. Of these 10 patients, 6 died of distant metastases 5 to 25 months
      after the recurrence. Three patients are still alive, with metastases to the
      bone, spleen, and pleura 1 to 24 months after the diagnosis of recurrence. Two
      patients are presently tumor free (T1N0, grade 3 and T3N2, grade 2), but only 1
      has survived beyond 5 years. CONCLUSIONS: Thymic neuroendocrine tumor must be
      regarded as a malignant neoplasm that is prone to metastasize to mediastinal
      lymph nodes and to distant sites, even after total excision. Neither T and N
      classification nor histologic grade has been successful in predicting the outcome
      of a patient with this tumor. More aggressive management, including adjuvant
      therapies and reexcision of subsequent tumors, may result in increased survival.

PMID- 10086552
TI  - Gelatin-resorcinol-formaldehyde-glutaraldehyde glue for sealing pulmonary air
      leaks during thoracoscopic operation.
AB  - BACKGROUND: Intraoperative pulmonary air leakage is one of the most troublesome
      complications in video-assisted thoracoscopic surgical procedures. We developed a
      sealing procedure using gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG)
      glue for pulmonary air leaks during such operations. METHODS: Formaldehyde
      glutaraldehyde (FG) jelly is prepared by mixing FG fluid with 2.5% sodium
      carboxymethyl cellulose to make the FG fluid viscous. We performed an adhesion
      strength test to determine the optimum ratio of gelatin-resorcinol mixture to FG
      jelly and then conducted an air leakage test on swine lung to compare the sealing
      effect between fibrin and GRFG glues. To study the histotoxicity of the GRFG
      glue, the sealant was applied to injured rabbit lung, and the rabbits were
      followed for 1 day to 188 days. For clinical studies, we developed an endosyringe
      to apply the GRFG glue on the target site during video-assisted thoracoscopic
      surgical procedures and used this technique in 21 patients with intraoperative
      air leaks. In addition, the side effects of GRFG glue application were studied in
      52 patients in whom glue was used in several ways during lung operations.
      RESULTS: The results of the adhesion-strength test favored a 2:1 gelatin
      resorcinol to FG ratio. The mean pressure required to produce air leakage was
      significantly higher with GRFG glue than with fibrin glue (p<0.001). No critical
      histologic damage was seen in the rabbit lung, and the glue persisted on the lung
      surface for 188 days after sealing. Clinical application of the glue in 21
      patients resulted in complete stoppage of air leakage during operation and long
      afterward, except in 1 patient with a late-onset lung fistula. The FG jelly
      helped prevent glue spillage at the target site, regardless of angle. A transient
      rise in temperature up to 38.60C was observed as a side effect 7 days after
      operation in 5 (9.6%) of the 52 patients. CONCLUSIONS: A GRFG glue using FG jelly
      seals pulmonary air leaks effectively, simply, and safely during video-assisted
      thoracoscopic surgical procedures.

PMID- 10086553
TI  - Recurrent and superior laryngeal nerves: a new look with implications for the
      esophageal surgeon.
AB  - BACKGROUND: Injury to the recurrent laryngeal nerve (RLN) is an unwelcome and not
      infrequent complication of operations on or near the upper thoracic or cervical
      esophagus. Because anatomic information useful to the surgeon is difficult to
      come by, the aim of this study was to reinvestigate and display the RLNs and
      superior laryngeal nerves in humans. METHODS: Postmortem en bloc specimens were
      studied: 23 by macroscopic dissection and 11 by large field serial histology. The
      nerves and their branches and supply areas were photographed at each step of
      dissection from the lateral (the surgeon's approach) and from the posterior
      aspect. RESULTS: The RLNs were 2- to 3-mm thick compact slack cords, sinuously
      passing upward within the lateral peritracheal, and less frequent periesophageal,
      loose connective tissue, the left RLN being closer to the tracheoesophageal
      groove than the right. Both RLNs gave off 8 to 14 branches, equally distributed
      to the esophagus and trachea. These were 2.5- to 1-cm long when stretched. The
      primarily identical pattern became unpredictable underneath the thyroid gland, an
      area that covered approximately 3 cm of the proximal esophagus. The RLN, still
      fairly robust (>1 mm) dipped, being firmly attached, into the larynx laterocaudad
      to the cricopharyngeus muscle. As the RLN and superior laryngeal nerves supply
      the same laryngeal muscles and mucosa, this twofold innervation may compensate
      for some sequelae of RLN injury. CONCLUSIONS: Displaying the RLNs, an important
      step in a variety of neck operations, dissection of the RLNs branches close to
      the esophagus and intestinocervical anastomosis as low as possible, will
      certainly reduce RLN injury.

PMID- 10086554
TI  - Unsuspected idiopathic mediastinal fibrosis complicating coronary bypass
      operation.
AB  - A 66-year-old woman was referred for coronary bypass operation to the left
      anterior descending and the circumflex arteries. She had a systemic inflammatory
      process of unknown origin. On opening the pericardium, fibrotic plaques
      encircling the entire ascending aorta were found. Aortic cannulation and proximal
      anastomosis of the planned vein graft were impossible. The right internal mammary
      was anastomosed to the left anterior descending artery, the left to the obtuse
      marginal after femoral arterial cannulation. Pathologic examination revealed
      idiopathic mediastinal fibrosis.

PMID- 10086555
TI  - Intracardiac tuberculoma.
AB  - We examined a case of endocardial tuberculoma at the proximal superior vena cava
      and the right atrium in a 17-year-old male patient. He had frequent palpitations
      and general weakness for about 7 months and was referred for evaluation of
      incessant atrial tachyarrhythmia. Results of echocardiography and magnetic
      resonance imaging showed an intracardiac mass, which was excised using
      cardiopulmonary bypass. Histology of the mass was consistent with the diagnosis
      of tuberculoma. The patient's postoperative course was uneventful and he was
      discharged with antituberculous medication. Five months after the operation, the
      patient was well without tachycardia, and follow-up echocardiography showed
      complete disappearance of the mass.

PMID- 10086556
TI  - Low cardiac output complicating pericardiectomy for pericardial tamponade.
AB  - Neoplastic involvement of the pericardium resulting in an effusion and subsequent
      tamponade is an emergency requiring prompt decompression, generally safely
      accomplished by subxiphoid pericardiectomy. However, the current case report
      describes a patient with florid pericardial tamponade who underwent surgical
      decompression with transient hemodynamic improvement, who then rapidly developed
      progressive, heart failure and death. This paradoxical response to pericardial
      decompression, similar to that seen occasionally with pericardiectomy in
      constrictive pericarditis, may be more frequent than currently appreciated. Its
      cause may relate to the sudden removal of the chronic external ventricular
      support from the effusion resulting in ventricular dilatation and failure.

PMID- 10086557
TI  - Surgical management of necrotizing Candida esophagitis.
AB  - Invasive esophageal candidiasis produced transmural necrosis leading to
      perforation in 2 patients aged 10 and 27 years. Both patients survived after
      esophageal resection and complete diversion. One patient with acute leukemia and
      neutropenia experienced systemic candidiasis, which resolved after esophagectomy.
      Esophagectomy and diversion for yeast-induced necrosis may lead to complete
      recovery and resolution of disseminated candidiasis when combined with systemic
      antifungal therapy.

PMID- 10086558
TI  - Aortopulmonary window with anomalous origin of the right coronary artery.
AB  - We report a case of an aortopulmonary window with a right coronary artery arising
      from the pulmonary trunk. This exceedingly rare anomaly with anomalous coronary
      artery presented without myocardial ischemia owing to the aortopulmonary window.
      The correct diagnosis was made by angiography and a successful surgical
      correction was performed.

PMID- 10086559
TI  - Reversal of protein-losing enteropathy after ligation of systemic-pulmonary
      shunt.
AB  - A 21-year-old white woman, born with a univentricular heart, had undergone staged
      procedures before Fontan correction. She then began to develop edema, protein
      losing enteropathy, and ascites refractory to diuretic therapy. Cardiac
      angiography showed a patent right Blalock-Taussig shunt, with turbulent
      cavopulmonary circulation. After undergoing an unsuccessful attempt at coil
      embolization she then underwent shunt ligation, with resolution of symptoms and
      normalization of protein levels. This report draws attention to the importance of
      cavopulmonary laminar flow to prevent the development of protein-losing
      enteropathy.

PMID- 10086560
TI  - Rescue revascularization for acute coronary occlusion late after radiotherapy.
AB  - Because radiation-induced coronary artery stenoses are frequently severe and
      located proximally, some patients are admitted in emergency. This report
      describes the case of a 47-year-old woman with radiation-induced stenosis of the
      left main coronary artery who presented with cardiac arrest during angiography.
      The patient was successfully treated using circulatory assistance and
      percutaneous transluminal coronary angioplasty as a bridge to coronary artery
      bypass grafting.

PMID- 10086561
TI  - Papillary endothelial hyperplasia presenting as a chest wall neoplasm.
AB  - Soft tissue hematomas generally resolve but may persist and develop into slow
      growing, organized masses. These chronic expanding hematomas are characterized by
      a pseudocapsule and a predominantly necrotic central cavity, with foci of newly
      formed capillaries. These have been called chronic expanding hematomas or
      Masson's papillary endothelial hyperplasia. These lesions can mimic vascular
      neoplasms and must be considered in the evaluation of expanding soft tissue
      vascular malformations.

PMID- 10086562
TI  - Chronic traumatic aortic pseudoaneurysm: resolution with observation.
AB  - Immediate operative repair is the most commonly recommended treatment for
      traumatic aortic ruptures, regardless of age or size of the lesion. We report a
      patient who presented with a large chronic aortic pseudoaneurysm and has been
      thus far managed nonoperatively with shrinkage of his lesion and no symptoms.

PMID- 10086563
TI  - An unusual combination of cardiovascular surgical disorders.
AB  - A 53-year-year-old man presented with aortic regurgitation, subvalvular and
      supravalvular aortic stenoses, and aneurysms involving the ascending aorta, the
      arch, and the innominate, right subclavian, and left common carotid arteries.
      Surgery consisted of resection of the obstructive lesions, replacement of the
      aortic valve, graft replacement of the ascending aorta, and the arch resection of
      innominate and subclavian artery aneurysms and reconstruction with a side limb to
      which the right carotid artery was anastomosed. The patient has remained
      asymptomatic with full employment.

PMID- 10086564
TI  - Repair of an aneurysm of the pulmonary trunk in a 65-year-old patient.
AB  - The case of a 65-year-old patient with asymptomaticaneurysm of the pulmonary
      trunk associated with severe insufficiency of the pulmonary valve and symptomatic
      coronary artery disease is presented. The surgical procedure included coronary
      artery bypass grafting, aneurysmectomy, and pulmonary artery replacement with
      implantation of a stentless bioprosthesis and lengthening of the root of the
      bioprosthesis with a reversed vascular Y prosthesis, which was anastomosed to the
      left and right pulmonary artery.

PMID- 10086565
TI  - Extracorporeal right to left atrial bypass to treat right ventricular failure.
AB  - Graft right ventricular failure after heart transplantation, secondary to
      preoperative functional pulmonary hypertension, was successfully managed in a 49
      year-old patient using an extracorporeal right to left atrial bypass. We comment
      on the case and discuss the type of mechanical assistance used.

PMID- 10086566
TI  - Cervical aortic arch with pseudocoarctation: presentation with spontaneous
      rupture.
AB  - A 23-year-old man presented with hypotension secondary to a left hemothorax.
      Diagnostic studies revealed a left cervical arch associated with a redundant
      tortuous pseudocoarctation in the proximal descending thoracic aorta. Operative
      exploration revealed an aortic rupture just proximal to the pseudocoarctation.
      Resection of the diseased aorta and tube graft replacement was performed under
      circulatory arrest. The patient was discharged home on the 12th postoperative
      day.

PMID- 10086567
TI  - Cardiac Whipple's disease without digestive symptoms.
AB  - Whipple's disease is a systemic illness that can affect the heart, causing
      pericarditis, myocarditis, and valvular endocarditis. We describe a 43-year-old
      man without gastrointestinal symptoms who underwent mitral and aortic valve
      replacement for endocarditis, in whom a diagnosis of Whipple's disease was made
      at operation.

PMID- 10086568
TI  - Penetrating trauma to the tricuspid valve and ventricular septum: delayed repair.
AB  - Penetrating cardiac trauma can result in a wide range of injuries to intracardiac
      structures. Missile injury, in particular, can cause damage in more than one
      cardiac chamber that may be difficult to identify at initial emergent operation.
      We report a case of late repair of traumatic ventricular septal defect and
      tricuspid valve perforation from gunshot wound. This case illustrates the
      importance of thorough examination of intracardiac anatomy during emergent and
      delayed repair for penetrating cardiac trauma.

PMID- 10086569
TI  - Incipient left ventricular rupture complicating anomalous left coronary artery.
AB  - A 4-month-old girl presented with 2 weeks of symptoms and physical signs of heart
      failure. Echocardiography demonstrated marked left ventricular dilation, thinning
      of the myocardium with anterolateral akinesis, mitral regurgitation, a moderate
      pericardial collection, and an anomalous left coronary artery from the pulmonary
      artery. At operation there was a tense hemopericardium and a site of imminent
      rupture through a transmural anterior infarction. The anomalous artery was
      reimplanted in the ascending aorta, and an extensive infarct resection and
      ventricular repair performed. Support with a left ventricular assist device was
      required for 3 days, but the infant subsequently made a satisfactory recovery.
      Left ventricular rupture is a very rare complication of this lesion, but should
      be considered if there is evidence of a pericardial collection.

PMID- 10086570
TI  - Saccular aneurysm of the aortic arch.

PMID- 10086571
TI  - Outpatient thoracoscopic limited sympathectomy for hyperhidrosis palmaris.
AB  - Thoracoscopic sympathectomy is considered the most effective treatment for
      hyperhidrosis palmaris. We have treated 1,043 cases of this disease by this
      method. We have developed an outpatient technique of thoracoscopic sympathectomy
      using electrocautery. This procedure has been used in 47 patients with
      hyperhidrosis palmaris. The early results have been favorable. We describe this
      fast, safe, economic, and effective method for the treatment of hyperhidrosis
      palmaris.

PMID- 10086572
TI  - Technique for repair of single-ventricle hearts with transposition of the great
      arteries and aortic arch hypoplasia.
AB  - We describe a modified technique of aortopulmonary anastomosis for palliative
      repair of hearts with a single left ventricle, a rudimentary right ventricle,
      transposition of the great vessels, and a hypoplastic aortic arch. This procedure
      creates an unobstructed left ventricular outflow tract and avoids the problems of
      spiral patch grafting and multiple patch enlargements of the ascending aorta and
      arch.

PMID- 10086573
TI  - Resection of anterior mediastinal masses through an infrasternal approach.
AB  - A video-assisted surgical technique for benign anterior mediastinal lesions is
      described. In 3 patients, the Laparolift system was used to lift the lower
      sternum before resection. This operation is less invasive and cosmetically more
      pleasing than median sternotomy. Unlike thoracoscopy, this procedure avoids
      opening the chest and can be performed in patients with pleural adhesions or
      pulmonary insufficiency in whom differential lung ventilation is impossible. At
      present, this technique is considered suitable only for benign lesions.

PMID- 10086574
TI  - The anatomical aspects of minimally invasive cardiac valve operations.
AB  - Cadaveric dissections were carried out to examine the relationship of the cardiac
      valve structures to the surface anatomy of the chest as it relates to our
      approaches to minimally invasive valvular operations. The techniques of upper
      hemisternotomy and lower hemisternotomy as used at our institution are described.

PMID- 10086575
TI  - Modified Blalock-Taussig shunt with compensatory properties.
AB  - Determination of the proper length of the tubular prosthesis is a major issue
      when performing a systemic-pulmonary artery shunt. The procedure is simplified by
      using a prosthesis with accordionlike properties. This was demonstrated in 7
      consecutive infants with complex congenital heart defects, in whom systemic
      pulmonary artery shunts were placed without early or late complications.

PMID- 10086576
TI  - A technique for insertion of self-expanding tracheal and bronchial stents.
AB  - We describe the use of skin markers, placed under radiologic control, to identify
      the limits of airway strictures as a reliable technique for the accurate
      placement of self-expanding stents. The technique has been used successfully in
      14 patients with extrinsic airway compression or bronchomalacia.

PMID- 10086577
TI  - Reminiscences of Vasilii I. Kolesov.
AB  - Vasilii I. Kolesov (1904-1992) as a military surgeon during the Siege of St.
      Petersburg (1941-1944) treated countless war casualties, and after the Siege, he
      also attended many survivors who suffered from coronary artery disease. It was
      probably this second mission that led him on February 25, 1964, to anastomose the
      left internal thoracic artery to a coronary. That operation ushered a new era in
      the modern treatment of coronary artery disease.

PMID- 10086578
TI  - Arterial grafts for coronary artery bypass grafting: biological characteristics,
      functional classification, and clinical choice.
AB  - Various arterial grafts have been used for coronary artery bypass grafting, but a
      unanimous opinion on how to best use these grafts has not been formed. Arterial
      grafts are not uniform in their biological characteristics. Differences between
      the perioperative behavior of the grafts and their long-term patency may be
      related to different characteristics. These characteristics should be taken into
      account in the use of arterial grafts, some of which are subject to more active
      pharmacologic intervention during and after operation to obtain satisfactory
      results. Clinical choice of grafts must be based on the general condition of the
      patient, the biological characteristics of the graft, the anatomy of the coronary
      artery, the match between the coronary artery and the graft, and technical
      considerations, including antispastic management.

PMID- 10086579
TI  - Arterial conduits.

PMID- 10086580
TI  - As originally published in 1992: Synchronous operation for ischemic cardiac and
      cerebrovascular disease: early results and long-term follow-up. Updated in 1998.

PMID- 10086581
TI  - Genesis of edema during orthograde and retrograde coronary perfusion.

PMID- 10086582
TI  - Simplified method for candidate selection for radial artery harvesting.

PMID- 10086583
TI  - Right ventricular infarction during left ventricular assist system support.

PMID- 10086584
TI  - Diagnosing upper plexus thoracic outlet syndrome with median motor nerve
      conduction studies.

PMID- 10086585
TI  - The "annular sandwich": a simple method of reinforcing a friable mitral valve
      annulus.

PMID- 10086586
TI  - Abciximab and the risk of bleeding during emergency cardiac operations.

PMID- 10086587
TI  - Leaflet preservation in mitral valve replacement with a tilting-disc valve.

PMID- 10086588
TI  - Arteriovenous fistula complicating chest tube insertion.

PMID- 10086589
TI  - Pericardial closure after intrapericardial pneumonectomy.

PMID- 10086590
TI  - Minimal incisions for aortic valve surgery.

PMID- 10086591
TI  - Defining neuropsychological deterioration after cardiac surgery.

PMID- 10086592
TI  - Additional maneuvers to improve mitral valve exposure through the conventional
      left atriotomy.

PMID- 10086593
TI  - Truncal valve repair in the neonate: fate of the valve.

PMID- 10086594
TI  - E-mail attachment problems.

PMID- 10086595
TI  - Proposed maximum permissible exposure limits for ultrashort laser pulses.
AB  - Recent studies have provided considerable ED50 data for both visible and near
      infrared wavelengths from single laser pulses below one nanosecond of exposure.
      The current ANSI Z136.1 standard does not offer an approved maximum permissible
      exposure limit for subnanosecond single laser pulses and the current suggested
      maximum permissible exposure limit may be overly conservative. Lacking an
      approved standard industrial, medical, educational, and military uses of these
      types of laser systems may be limited or prohibited. A new set of laser maximum
      permissible exposure limits for subnanosecond visible and near infrared single
      laser pulses is recommended, along with the steps taken to develop the proposed
      standard.

PMID- 10086596
TI  - A biosphere modeling methodology for dose assessments of the potential Yucca
      Mountain deep geological high level radioactive waste repository.
AB  - Recent developments in performance standards for proposed high level radioactive
      waste disposal at Yucca Mountain suggest that health risk or dose rate limits
      will likely be part of future standards. Approaches to the development of
      biosphere modeling and dose assessments for Yucca Mountain have been relatively
      lacking in previous performance assessments due to the absence of such a
      requirement. This paper describes a practical methodology used to develop a
      biosphere model appropriate for calculating doses from use of well water by
      hypothetical individuals due to discharges of contaminated groundwater into a
      deep well. The biosphere model methodology, developed in parallel with the
      BIOMOVS II international study, allows a transparent recording of the decisions
      at each step, from the specification of the biosphere assessment context through
      to model development and analysis of results. A list of features, events, and
      processes relevant to Yucca Mountain was recorded and an interaction matrix
      developed to help identify relationships between them. Special consideration was
      given to critical/potential exposure group issues and approaches. The conceptual
      model of the biosphere system was then developed, based on the interaction
      matrix, to show how radionuclides migrate and accumulate in the biosphere media
      and result in potential exposure pathways. A mathematical dose assessment model
      was specified using the flexible AMBER software application, which allows users
      to construct their own compartment models. The starting point for the biosphere
      calculations was a unit flux of each radionuclide from the groundwater in the
      geosphere into the drinking water in the well. For each of the 26 radionuclides
      considered, the most significant exposure pathways for hypothetical individuals
      were identified. For 14 of the radionuclides, the primary exposure pathways were
      identified as consumption of various crops and animal products following assumed
      agricultural use of the contaminated water derived from the deep well. Inhalation
      of dust (11 radionuclides) and external irradiation (1 radionuclide) were also
      identified as significant exposure modes. Contribution to the total flux to dose
      conversion factor from the drinking water pathway for each radionuclide was also
      assessed and for most radionuclides was found to be less than 10% of the total
      flux to dose conversion factor summed across all pathways. Some of the
      uncertainties related to the results were considered. The biosphere modeling
      results have been applied within an EPRI Total Systems Performance Assessment of
      Yucca Mountain. Conclusions and recommendations for future performance
      assessments are provided.

PMID- 10086597
TI  - Plutonium excretion in urine of residents living near the Rocky Flats
      Environmental Technology Site.
AB  - An assessment of current levels of 239Pu in individuals living near the Rocky
      Flats Environmental Technology Site was conducted. Long-term residents of areas
      adjacent to the Site, as well as people living well beyond any expected influence
      of the site, provided urine samples, which were analyzed by fission track
      analysis for the levels of 239Pu. The Rocky Flats Environmental Technology Site
      vicinity participants were selected for maximum possible exposure to
      environmental plutonium by virtue of residence location, length of residence,
      age, and outdoor lifestyle. The mean 239Pu excretion rate in urine estimated for
      the entire Rocky Flats group was 1.1 microBq d(-1), in contrast to that estimated
      for the background group (0.85 microBq d(-1)). The estimated median 239Pu
      excretion rate for the Rocky Flats group was 1.1 microBq d(-1), compared to 0.54
      microBq d(-1) for the background group. Both parametric and non-parametric tests
      indicated that these differences were not statistically significant (alpha =
      0.05). Measured levels of 239Pu in urine from the Rocky Flats group were low and
      well within the range of reported "background" values, indicating small doses and
      low health risks. The fission track analysis technique may not be sufficiently
      accurate or precise to allow definitive comparisons between two groups of
      subjects with near-background levels of 239Pu in urine.

PMID- 10086598
TI  - Lung exposure from inhalation of radon progeny: calculated from in vivo
      measurements of 210Pb in the skull.
AB  - To calculate the radiation dose to the lungs from the inhalation of radon and its
      short-lived progeny, an accurate estimate of cumulative exposure is necessary. In
      this preliminary study, the content of 210Pb in the skeleton is used to obtain a
      measure of integrated exposure to the lungs of people living in homes with above
      average concentrations of radon. Measurements of skeletal 210Pb made in vivo
      allow the exposed individuals to become, in effect, their own "samplers" and
      "dosimeters" through the normal physical and physiological processes of
      inhalation, deposition, and retention. 210Pb measurements have been made on 40
      subjects whose homes have above average levels of radon. These data are used to
      obtain their cumulative lung exposures, defined as RLM (Respiratory Level
      Months). RLM is calculated from the numbers of atoms of RaA, RaB, and RaC,C'
      deposited in their respiratory systems over the time periods lived in the
      surveyed homes. The RLM values obtained are not significantly different than
      conventional WLM exposures calculated for the same time periods.

PMID- 10086599
TI  - Monte Carlo estimation of absorbed dose to organs in diagnostic radiology.
AB  - A method to estimate the absorbed dose to organs in diagnostic radiology was
      developed. The method is based on Monte Carlo techniques and has been prepared as
      a tool that can be adapted to any type of examination or view and which is
      readily available since it is used in a personal computer and not as a list of
      numerical results. It has been developed with the EGS4 system for static
      examinations in diagnostic radiology. A study was made of the absorbed doses to
      different parts of the head during a conventional x-ray examination. Simulation
      was performed for different arrangements (monoenergetic beam, spectrum, different
      number of histories, different size of cells, etc.). The method is capable of
      estimating doses in agreement with those measured experimentally and those
      obtained by other authors.

PMID- 10086600
TI  - Implications of a two-stage clonal expansion model to indoor radon risk
      assessment.
AB  - Spreadsheet macro programs for calculations of exact hazard and probability of
      having contracted cancer were used to study the implications of the lung cancer
      model of Moolgavkar et al. Excess lifetime risk ELR and loss of life expectancy
      LLE were calculated from the annual values of hazard and probability, using
      published life tables. The influence of various factors on ELR and LLE was
      studied, as well as the lifetime risk projection in epidemiological studies. At
      indoor concentrations, ELR and LLE are coarsely proportional to lifetime
      exposure. The main factors determining the proportionality coefficient are 1.
      Smoking status, 2. General life expectancy, 3. Exposure schedule, and 4. Sex. For
      constant domestic exposure, the sex is less important, because the longer life of
      women is compensated by the lower hazard. ELR and LLE for a population with 30%
      smokers and life expectancies of 72.1 y and 79.5 y for men and women,
      respectively, are 56 per million per WLM and 860 y per million per WLM,
      respectively. For an exposure schedule with one high radon period, the mean age
      during the period becomes important, and the age-specific values for men and
      women differ from each other. Furthermore, the model predicts that case-control
      epidemiological studies overestimate the lifetime risk by an amount which may
      arise to several tens of percent.

PMID- 10086601
TI  - Occupational doses from radon in Spanish spas.
AB  - Recent international recommendations have included exposure to natural radiation
      as one of the sources to monitor in certain occupationally exposed groups. Among
      those mentioned are workers in thermal spas, who may be exposed to high radiation
      doses due to the high concentration of radon in the indoor air of the spa. This
      paper presents the methodology and the results of an evaluation of radiation
      doses to the staff in different thermal spas in Spain. Different series of
      samples were collected and measurements made for the radon concentrations in
      water in 54 spas and in air in 20 spas. In six of the latter group, the air radon
      concentration was studied in different working areas occupied by the employees.
      The radon concentrations in water were between <2 and 775 x 10(3) Bq m(-3). The
      radon concentrations in air were between <10 and 5,200 Bq m(-3). The latter were
      used to estimate the dose received by each occupational group in the spa by
      taking into account the radon concentration in their main working area. By means
      of an exposure-dose conversion factor of 1.43 Sv per J h m(-3), the estimated
      effective doses were found to lie between 1 and 44 mSv y(-1). This upper limit is
      higher than the recommended annual limit of 20 mSv y(-1) for an occupational
      dose.

PMID- 10086602
TI  - Some problems in the skeletal dosimetry of bone-seeking radionuclides.
AB  - There are fundamental problems with the calculation of radiation doses to the
      skeleton from internal emitters deposited in bone. Some of these include dose
      inhomogeneities, identity of cells at risk and their dynamics, changing
      deposition patterns of bone-seeking radionuclides with time after exposure,
      seemingly unique responses of the skeleton to each deposited radionuclide, the
      role of radioactive progeny produced by deposited emitters and their individual
      dynamics and effects, different responses of mammals of different ages at
      exposure to identical dosages, different responses to different chemical forms of
      a given radionuclide, and different responses to an identical dose from a given
      radionuclide at different dose-rates. This situation makes it necessary to choose
      some common dose parameter that will allow the overall effects of different
      radionuclides to be compared directly so that projected effects of each of them
      in humans can be estimated. For radiation protection purposes, it appears
      premature to abandon the concept of average skeletal dose (which appears to be a
      practical compromise for use) until an undelusive, non-artificial and uncontrived
      method of calculating absorbed dose to the appropriate cells in bone is developed
      that fulfills the requirement of equal cancer response for equal skeletal dose
      for all circumstances.

PMID- 10086603
TI  - A comparison of minimum detectable and proposed maximum allowable soil
      concentration cleanup levels for selected radionuclides.
AB  - Regulations on the release of a radioactively contaminated site for unrestricted
      use are currently being established by the Environmental Protection Agency. The
      effective dose equivalent rate limit for the reasonably maximally exposed
      individual was proposed at 0.15 mSv y(-1). The purpose of this study is to
      investigate whether or not maximum allowable soil concentrations of common
      radionuclides corresponding to 0.15 mSv y(-1) are readily detectable. These
      maximum allowable soil concentrations were estimated using RESRAD. The RESRAD
      estimates account for an effective dose equivalent rate from external radiation
      plus the committed effective dose equivalent rate from internal radiation
      delivering 0.15 mSv y(-1) to the reasonably maximally exposed individual. For
      Michigan and Arizona soil, the minimum detectable activities were calculated for
      a few radionuclides and compared to the RESRAD estimated maximum allowable
      concentrations. Considering only gamma-ray spectroscopy, this study found no
      evidence that concentrations of gamma-ray emitting radionuclides in soil
      contributing to 0.15 mSv y(-1) were undetectable.

PMID- 10086604
TI  - Continuous measurements of outdoor 222Rn concentrations for three years at one
      location in Colorado.
AB  - Measurements were made of 222Rn concentrations outdoors in Ft. Collins, Colorado,
      using a continuously sampling scintillation flask between January 1993 and
      December 1995. These data were analyzed for hourly, daily, and seasonal
      variations. The average 222Rn concentration at 1 m above the ground was 18 +/- 10
      Bq m(-3) with a geometric mean of 15 Bq m(-3) and a geometric standard deviation
      of 1.7. Hourly averaged data indicated a diurnal pattern with the outdoor 222Rn
      concentration reaching a maximum in the early morning between 4:00 a.m. and 6:00
      a.m. and a broad minimum between 1:00 p.m. and 4:00 p.m. in the afternoon. An
      analysis also indicated that the outdoor 222Rn concentrations were consistently
      lowest during the spring (March and April) and highest during the late summer
      (July-September).

PMID- 10086605
TI  - Decontamination in a Russian settlement.
AB  - Decontamination was carried out in an area with three houses in Novo Bobovichi,
      Bryansk region, Russia, in the autumn of 1995. It was demonstrated that
      significant reductions in the dose rate both indoor (DRF = 0.34) and outdoor (DRF
      = 0.20) can be achieved when a controlled cleaning is undertaken. This paper
      describes the decontamination work carried out and the results obtained. The
      roofs of the houses were swept and cleaned by special roof cleaning equipment.
      The soil around the houses was removed by hand while carefully monitoring the
      ground for residual contamination. By monitoring the decline in the dose rate
      during the different stages of the work the dose reducing effect of each action
      has been measured.

PMID- 10086606
TI  - Natural background radiation, altitude, and oxygen toxicity.

PMID- 10086607
TI  - Comments on "Threshold models in radiation carcinogenesis" by D.G. Hoel and P.
      Li.

PMID- 10086608
TI  - Thorotrast and calciphylactic scleroderma.

PMID- 10086609
TI  - Academic course selection.

PMID- 10086610
TI  - Response to the Lubin rejoinder.

PMID- 10086611
TI  - Response to "Rejoinder" by Field et al.

PMID- 10086612
TI  - Virtual laryngoscopy.
AB  - Virtual endoscopy enables computer-generated 3-dimensional visualization of a
      cavity by reconstructing 2-dimensional computed tomographic or magnetic resonance
      data. The technique has been used experimentally to study the colon, bronchi,
      ears, and other structures. Here, virtual laryngoscopies were created from the
      cross-sectional image data of 3 patients. The cases represented a normal airway,
      a squamous cell carcinoma of the glottic fold, and a posterior glottic stenosis.
      These reconstructions included extraluminal anatomy that is not typical of
      current virtual endoscopic techniques. The 2-dimensional computed tomographic and
      magnetic resonance images of the patients underwent post-processing for 3
      dimensional reconstruction. The resulting models were imported into an
      experimental virtual endoscopy program for 1) airway lumen generation and 2)
      interactive viewing. Though they could not be used for biopsy, the virtual
      laryngoscopies provided, in a noninvasive fashion, good simulation of endoscopy.
      Virtual endoscopy also gave the added benefits of the ability to assess the
      transmural extent of disease and view the airway distal to areas of luminal
      compromise. This technology may well provide clinical benefit in preoperative
      planning, staging, and intraprocedural guidance for head and neck disease and
      merits further study.

PMID- 10086613
TI  - Selective laryngeal adductor denervation-reinnervation: a new surgical treatment
      for adductor spasmodic dysphonia.
AB  - During the past decade, botulinum toxin (Botox) has emerged as the accepted
      treatment for adductor spasmodic dysphonia (ASD). This therapy, which produces
      bilateral weakness of the thyroarytenoid muscle, undoubtedly produces physiologic
      effects that are beneficial to patients with ASD. However, it also has important
      limitations, including the need for repeated injections, the unpredictable
      relationship between dosage and response, and the possibility of short-term
      swallowing and voice problems. In this study, we will report our preliminary
      experience with a new surgical treatment for ASD. In this new procedure, the
      adductor branch of the recurrent laryngeal nerve is selectively denervated
      bilaterally, and its distal nerve stumps are reinnervated with branches of the
      ansa cervicalis nerve. Each of the patients was followed for at least 12 months;
      the median follow-up is 36 months. The outcome of the operation in 21 consecutive
      patients is reported. Nineteen of the 21 patients were judged to have an overall
      severity of dysphonia that was "absent to mild" following the procedure. Only 1
      patient underwent further treatment with Botox postoperatively. The implications
      of this new procedure for ASD are discussed.

PMID- 10086614
TI  - Morphology of the human larynx during the first five years of life studied on
      whole organ serial sections.
AB  - The morphologic development of the human larynx during the first years of life is
      poorly understood to date. This study used plastinated whole organ serial
      sections to determine the growth and structure of the infant larynx. The larynges
      of 43 children 1 to 60 months old were plastinated. Whole organ serial sections
      were obtained by cutting the resulting specimen with a diamond band saw. The
      slices were then submitted to computer-assisted morphometric investigation. We
      found that the subglottic airway rapidly increases in size during the first 2
      years of life. Further growth follows a linear mode. The relative proportion of
      the mucosal lining decreases likewise. In contrast to that in adults, and
      comparable to that in most mammals, the cartilaginous glottis accounts for 60% to
      75% of the vocal folds' length at <2 years. No sexual dimorphism of the larynx
      exists during childhood. This study supplies detailed morphometric data on the
      growth and structure of the human larynx during the first years of life. It is
      the first to use plastinated whole organ serial sections for morphology of the
      pediatric larynx. Therefore, this study provides quantitative anatomic data of
      clinical interest that have not been available to date.

PMID- 10086615
TI  - Hypoglossal nerve transfer for laryngeal reinnervation: a preliminary study.
AB  - The hypoglossal nerve is a logical donor nerve for hemilaryngeal reinnervation
      because 1) its activity coincides with normal laryngeal adduction during speech
      and deglutition; 2) it is a large nerve with many axons; and 3) donor site
      morbidity is low. This method of laryngeal reinnervation has not been previously
      reported. Previous studies using the ansa cervicalis for reinnervation have
      failed to show spontaneous activity. Hypoglossal-to-recurrent laryngeal nerve
      anastomosis was performed on a series of 5 dogs. The vocal folds were viewed
      monthly, with the animals awake, by infraglottic examination through a permanent
      tracheostomy. One dog failed due to technical error. The remaining 4 dogs began
      to exhibit spontaneous vocal fold adduction within 2 to 4 months. Vocal fold
      motion was synchronous with spontaneous tongue motion. Complete glottic closure
      was seen during swallowing at 3 to 5 months. Intraglottic pressure measurements
      following reinnervation were normal. Hypoglossal nerve transfer appears to be
      capable of providing functional adduction to the paralyzed hemilarynx. The
      potential advantages and disadvantages of this new technique are discussed.

PMID- 10086616
TI  - Expression pattern of the plasminogen activator-plasmin system in human
      cholesteatoma.
AB  - The plasminogen activator-plasmin system plays a pivotal role in the delicately
      regulated process of extracellular matrix remodeling. Recent studies have shown
      that an imbalance of proteolytic enzymes over specific inhibitors in this system
      may lead to an aggressive, expanding, and infiltrating cellular phenotype. As
      cholesteatoma resembles a tumor in many ways, we investigated the pattern of
      expression for members of the plasminogen activator-plasmin system in 12 human
      cholesteatomas, using immunohistochemistry. As controls, 3 tympanic membranes and
      4 ear canal skin specimens were used. In contrast to the tympanic membranes, all
      cholesteatoma specimens showed a strong expression of plasminogen at the basal
      epithelial cell layers. In ear canal skin, only the basal surface of the most
      basal epithelia stained discretely positive. The urokinase-type plasminogen
      activator (uPA) could be detected in the basal stratum of the cholesteatoma
      matrix and in the surrounding granulation tissue, while tissue-type plasminogen
      activator (tPA) was not detectable at all. Plasminogen activator inhibitor-1 (PAI
      1) was expressed in both the granulation tissue and the granular cell layer of
      the matrix, but not in the basal epithelial cells; PAI-2 showed a pericellular
      expression pattern in the subbasal and granular cell layers. Neither uPA, tPA,
      nor the PAIs could be detected in tympanic membrane controls; ear canal skin
      showed the same staining pattern as cholesteatoma only for PAI-2. Our data
      demonstrate that there is a clear imbalance in favor of proteolytic activity in
      the basal epithelial layers of the cholesteatoma matrix, which might at least
      partly account for the aggressive behavior of this tumorlike lesion. Further, the
      pattern of expression resembles the pattern described for several epithelial
      malignancies.

PMID- 10086617
TI  - Rare middle ear anomaly in a patient with Turner's syndrome.
AB  - A patient with Turner's syndrome presented with a rare anomaly of absent oval
      window, inferiorly placed facial nerve, and abnormal stapes. To our knowledge,
      this is the first report of this combination of malformations.

PMID- 10086618
TI  - Murine model of autoimmune hearing loss induced by myelin protein P0.
AB  - Myelin protein P0 has been identified as an autoantigen in inner ear diseases. In
      order to study autoimmune hearing loss, we performed brain stem auditory-evoked
      potential (BAEP) studies on P0-sensitized mice. Two P0-sensitized mice showed
      hunched posture, poor coat, loss of body weight, and abnormal walking with a
      waddling gait. About 25% of the P0-sensitized mice developed hearing loss. In the
      BAEP study, peak latencies of waves I, III, and V and the interpeak latency I-III
      were prolonged in the P0-sensitized hearing loss group of mice. Hearing
      thresholds were elevated in this group of mice in comparison with the control
      mice. Inflammatory cell infiltration was observed in the cochlear nerve region,
      and a reduced number of spiral ganglion cells was also detected. These results
      suggest that P0-sensitized mice are a useful model for studying autoimmune
      inflammation of the peripheral portion of the auditory system.

PMID- 10086619
TI  - Three-dimensional quantification of "still" points during normal facial movement.
AB  - This study investigated the 3-dimensional displacement of points on the face that
      were thought to be still during facial movement. These points are currently used
      to measure displacement of moving facial regions during assessment of normal
      facial movement and treatment interventions following facial nerve paralysis. It
      is, however, unknown if these places are "still" points. The Expert Vision Motion
      Analysis System was used to collect and analyze data on 42 normal subjects during
      facial movement. No point on the face was found to be still during facial
      expression. However, several points were present with very small movements for
      each individual expression. These were termed "reference" points. These small
      movements may be the result of system noise, physiological tremor, skin movement,
      or head-holder movement during facial expressions. Future studies of the
      displacement of the markers during facial movement in both normal subjects and
      patients with facial nerve paralysis may take into account the contribution of
      the "reference" point displacements to the overall facial movement.

PMID- 10086620
TI  - Multifocal cholesteatoma of the external auditory canal following blast injury.
AB  - Posttraumatic cholesteatoma of the external auditory canal is a rare condition
      that may present years after the original injury. A unique case of multifocal
      cholesteatoma of the external auditory canal following blast injury is presented
      and discussed.

PMID- 10086621
TI  - Vestibular responses of normal and hydropic ears of the guinea pig to middle ear
      pressure application.
AB  - The pressure in the middle ears of normal and hydropic guinea pig ears was
      increased, and nystagmographic recordings were compared. Two-month unilateral
      hydropic guinea pigs and normal control guinea pigs underwent pressure treatments
      in which pressure was introduced into the middle ear. Significantly lower
      pressure was needed to elicit nystagmus in hydropic ears (mean 1.00 psi or 70.3
      cm H2O) compared with normal control ears (mean 1.27 psi or 89.3 cm H2O). All of
      the normal control guinea pigs showed fast phase nystagmus toward the pressure
      applied side, while hydropic guinea pigs showed nystagmus toward the normal ear.
      The duration of nystagmus was slightly longer in hydropic animals than in normal
      control animals. The slow phase velocity was slightly higher in the hydropic
      guinea pigs. Histologic examination revealed that the vestibular sensory cells
      remained normal and that changes in the organ of Corti were similar between the
      hydropic ears with and without pressure treatment at equal survival times.

PMID- 10086622
TI  - Rat eustachian tube and its musculature.
AB  - The objective of this study was to evaluate the anatomy of the eustachian tube
      (ET) of the rat and the paratubal musculature. Microdissection and serial
      sections were used. The ET consists of collapsible membranous and
      membranocartilaginous segments and a noncollapsible bony segment. Tubal muscles
      are attached to the collapsible part; the salpingopharyngeus muscle (SPM) is well
      developed and consists of 3 distinct groups of muscle fibers; the tensor veli
      palatini muscle (TVPM) consists of 2 functionally different groups of fibers, but
      only 1 group assists in opening the ET. Attachment of the fibers of the SPM and
      TVPM that are involved in tubal opening is confined to the dorsal portion of the
      ET. This finding, together with the earlier observation that this part is mainly
      lined by squamous epithelium, strongly suggests that the dorsal part has a
      ventilatory function. The ventral portion of the ET, which is lined by ciliated
      secretory epithelium and lacks the attachment of muscle fibers that can dilate
      the lumen, is assumed to serve clearance. The anatomic position of the levator
      veli palatini muscle suggests that this muscle contributes to the protective
      function of the ET. These findings are discussed with regard to the ET in humans.

PMID- 10086623
TI  - Effect of thyroplasty on laryngeal airflow.
AB  - Thyroplasty has virtually replaced Teflon injection as the procedure of choice
      for treatment of the unilateral paralyzed vocal cord. Previous studies have shown
      that Teflon injection, by stiffening the vocal cord, decreases the extrathoracic
      airway obstruction occasionally measured by pulmonary function testing in
      patients with unilateral vocal cord paralysis. We became interested in the effect
      of thyroplasty on extrathoracic airflow. In this prospective study, patients
      underwent prethyroplasty and postthyroplasty pulmonary function testing. Flow
      volume loops combined with traditional spirometry were used. Postoperative
      pulmonary function tests were performed at least 2 months after surgery to allow
      resolution of surgical edema. Our study results support the previous finding that
      vocal cord paralysis alone causes some degree of extrathoracic obstruction.
      However, in contrast to Teflon injection, thyroplasty decreased extrathoracic
      airflow in all but 1 patient, and by criteria based on the ratio of the
      midexpiratory flow to the midinspiratory flow, caused new postoperative
      extrathoracic obstruction in 27% of patients. Symptomatic evidence of this
      obstruction may be more evident in those active patients with more ventilatory
      demand.

PMID- 10086624
TI  - Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients
      with chronic maxillary sinusitis.
AB  - Our objective was to study the immune response to 2 anaerobic bacteria in
      patients with chronic maxillary sinusitis. Immunoglobulin G class antibody titers
      to Fusobacterium nucleatum and Prevotella intermedia were measured by enzyme
      linked immunosorbent assay. Serum levels in the patients were determined on the
      day sinus aspiration for culture was done, and 75 to 90 days later, after
      completion of antimicrobial therapy, Prevotella intermedia was isolated from 16
      aspirates, and F. nucleatum from 12. Median antibody levels at day 1 for F.
      nucleatum and P. intermedia were significantly higher in patients whose serum
      aspirates harbored these organisms than at days 75 to 90 in those who were cured
      (p < .05). However, the levels stayed elevated in the 5 patients who did not
      improve. The elevated antibody levels to F. nucleatum and P. intermedia, known
      oral pathogens, suggest a potential pathogenic role for these organisms in
      chronic maxillary sinusitis.

PMID- 10086625
TI  - The "sign of the rising tide" during swallowing fiberoscopy: a specific
      manifestation of Zenker's diverticulum.
AB  - Pooling of secretions in the hypopharynx is a common sign of an impaired upper
      esophageal sphincter. Until now, no specific manifestation, observed by flexible
      laryngoscopy, of Zenker's diverticulum has been reported. Direct visualization of
      the diverticulum can be missed during flexible laryngoscopic examination. In this
      series of 12 patients with hypopharyngeal diverticulum, we have described a
      manifestation of Zenker's diverticulum obtained on videofiberoscopy during cream
      swallowing. We have called it the "sign of the rising tide" because it describes
      the backup of cream visible in the hypopharynx as a wave after its complete
      disappearance. Barium swallow study is necessary to confirm the presumptive
      diagnosis. This relevant manifestation seems to be specific for Zenker's
      diverticulum, since it is not observed in other upper esophageal sphincter
      disorders, and it disappears when surgical treatment is successful.

PMID- 10086626
TI  - Localization of zinc in the rat submandibular gland and the effect of its
      deficiency on salivary secretion.
AB  - To clarify the role of zinc in the mechanism of salivary secretion, the effects
      of zinc deficiency on the morphologic findings and secretory function of the
      salivary gland were investigated with a rat model of chronic zinc deficiency,
      prepared by feeding a zinc-deficient diet, and a rat model of acute zinc
      deficiency, prepared by administration of a zinc chelator, dithizone. In rats
      with chronic zinc deficiency, the granule production in the granular duct cells
      was decreased, but the glandular epithelial cells and myoepithelial cells showed
      no degenerative or other destructive morphologic changes. The degranulation of
      the granular duct cells and acinar cells in response to acetylcholine
      hydrochloride seen in control rats was strongly inhibited in rats with acute and
      chronic zinc deficiency. The contractile response of the actin microfilament
      bundles in the myoepithelial cells to acetylcholine seen in the control rats was
      also absent in the zinc-deficient rats. Further, electron microscopy of the
      submandibular gland stained by Timm's method disclosed prominent zinc
      localization at the membrane surface, granules, and vesicles of the glandular
      epithelial cells and in the pits of the myoepithelial cells. These findings
      suggest that zinc, together with many zinc-dependent enzymes, is closely involved
      in the production and degranulation of secretory granules in the glandular
      epithelial cells, and also in the contraction of the myoepithelial cells in the
      submandibular gland.

PMID- 10086627
TI  - Effect of sleep state on the laryngeal chemoreflex in neonatal piglets.
AB  - The laryngeal chemoreflex (LCR) is a brain stem-mediated response that is a
      potential mechanism for sudden infant death syndrome. The vast majority of sudden
      infant death occurs during sleep, yet it remains to be established whether there
      is a particular sleep state that makes an infant animal more susceptible to
      apneic events via the LCR. The purpose of this study was to investigate the LCR
      during different sleep states in the neonatal piglet. In this study, continuous
      physiologic monitoring and electroencephalographic, electro-oculographic, and
      electromyographic techniques were utilized to study neonatal piglets during a
      hypnotic induced sleep model. Propofol drip anesthetic was utilized to provide an
      anesthetic state and was titrated for dose-dependent sedation. The LCR was
      initiated in 11 animals during quiet sleep, rapid eye movement sleep, and the
      anesthetic state. Baseline respiratory and cardiovascular responses were
      measured. Durations of apnea were recorded and compared. This study found that
      despite known physiologic differences in respiratory control during different
      sleep states as compared to the anesthetic state, there appears to be no
      increased risk of profound apnea in one state versus another in piglets 19 to 28
      days old.

PMID- 10086628
TI  - Microbial extracranial aneurysm of the internal carotid artery: complication of
      cervical lymphadenitis.

PMID- 10086629
TI  - Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the
      head and neck.
AB  - Papillary squamous cell carcinoma and verrucous squamous cell carcinoma of the
      head and neck may be confused. The clinicopathological profile of the two
      neoplasms is presented and the differential diagnosis is discussed. A correct
      diagnosis is imperative in order to institute the most appropriate treatment.

PMID- 10086630
TI  - Treatment of chronic hepatitis C virus infection: the end of an era.

PMID- 10086631
TI  - Endoscopic approach to HIV-associated diarrhea: how far is far enough?

PMID- 10086632
TI  - Budd-Chiari syndrome: is TIPS tops?

PMID- 10086633
TI  - Severe persistent constipation.

PMID- 10086634
TI  - Challenging problems presenting as constipation.
AB  - Patients who seek medical care for constipation present challenges which may
      involve communication problems, difficulties in diagnosis, lack of optimal
      therapy, uncorrectable underlying disorders, or psychiatric issues which
      complicated management. This review describes some of these challenges, and
      presents management approaches that may increase the likelihood of satisfactory
      treatment outcomes. Situations which are reviewed include the diagnostic
      evaluation of the new patient with constipation; syndromes of uncertain
      pathophysiology including irritable bowel syndrome, slow transit constipation,
      and pelvic floor dysfunction; constipation associated with neurologic disorders
      including spinal cord injury, Parkinson's disease, and multiple sclerosis; and
      psychiatric issues which complicate the management of constipation, including
      recognition of associated psychiatric diseases, unusual attitudes toward bowel
      function, eating disorders, and referral for psychiatric care.

PMID- 10086635
TI  - Colorectal cancer and the Muir-Torre syndrome in a Gypsy family: a review.
AB  - OBJECTIVES: The Muir-Torre syndrome (MTS) is characterized by an autosomal
      dominant predilection to sebaceous adenomas, sebaceous carcinomas, and multiple
      keratoacanthomas, in concert with the cancer phenotype of hereditary nonpolyposis
      colorectal cancer (HNPCC). Proof that patients showing a familial aggregation of
      MTS's cutaneous signs in combination with a specific pattern of visceral cancers
      which are consonant with an HNPCC diagnosis has been buttressed by the discovery
      of hMSH2 and hMLH1 germ-line mutations in such families. Our purpose in this
      investigation was to determine the germ-line mutation in a Gypsy family with MTS
      in concert with HNPCC cancer features, and to provide genetic counseling. An
      added objective for this paper is to review the literature on MTS. METHODS: We
      describe a Gypsy family with MTS in concert with HNPCC cancer features, as well
      as the molecular genetic and genetic counseling procedures used in the interest
      of improved compliance with cancer control recommendations. We review the
      clinical phenotype, natural history, and molecular genetics involved in the MTS
      variant HNPCC. RESULTS: An hMSH2 germ-line mutation was identified as the culprit
      germ-line mutation in this family. CONCLUSIONS: The presence of the hMSH2 germ
      line mutation in this family provides powerful predictability of colorectal and
      other HNPCC integral cancers. The gastroenterologist must assume an important
      role in the diagnosis and management of MTS.

PMID- 10086636
TI  - Chronic hepatitis C and interferon alpha: conventional and cumulative meta
      analyses of randomized controlled trials.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical usefulness of
      surrogate markers of the interferon effect (i.e., alanine aminotransferase levels
      and serum HCV-RNA status) as predictors of long term response, and to identify
      the optimal schedule of treatment for patients with chronic hepatitis C by means
      of meta-analysis. METHODS: Pertinent randomized clinical trials and prospective
      studies were selected using MEDLINE (1986-1996), a reference list from published
      articles or reviews. Twenty-six prospective studies reporting data on surrogate
      markers of interferon response were selected. Thirty-nine trials comparing
      interferon alpha to no treatment and 25 trials comparing different schedules of
      interferon were reviewed. Conventional meta-analysis according to the DerSimonian
      and Laird method was used for the pooling of results. RESULTS: The pooled
      probability of late relapse among sustained responders with negative serum HCV
      RNA 6 months after treatment was very low (8.7%; 95% confidence interval 5.8
      11.6%). The overall risk difference between treated and control groups was 16.63%
      (95% confidence interval 11.95-21.31%) for sustained aminotransferase
      normalization. Therapy with higher interferon dose compared with standard dose
      significantly improves the rate of sustained response (pooled risk difference
      10.56%, 95% CI 5.47-15.65%). Cumulative meta-analyses suggest that a clear dose
      response relationship exists across a wide range of interferon dosages. The
      multivariate meta-regression model confirms that the total interferon dose is an
      independent predictor of sustained response and that it seems more important than
      the length of treatment. CONCLUSIONS: Testing for serum HCV-RNA, 6 months after
      interferon therapy in sustained biochemical responders, is useful for predicting
      long term response. The current standard total interferon dose of 234 mega-units
      is suboptimal. Further trials that directly compare different schedules of
      treatment are needed.

PMID- 10086637
TI  - A prospective study of endoscopy in HIV-associated diarrhea.
AB  - OBJECTIVE: Diarrhea commonly occurs in persons with human immunodeficiency virus
      (HIV) infection. The optimal use of endoscopic procedures remains poorly studied
      for patients with HIV-related diarrhea. The purpose of this study is to compare
      the diagnostic yield of a complete endoscopic work-up including an
      esophagogastroduodenoscopy and colonoscopy to a more limited approach of biopsies
      obtainable by flexible sigmoidoscopy. METHODS: A prospective study of 79 patients
      with HIV-related diarrhea. Upper endoscopy and colonoscopy were performed with
      tissue biopsies labelled according to location within the colon or small
      intestine. RESULTS: A new infection was diagnosed in 22 of 79 patients (28%).
      Biopsy of the left colon yielded an enteric pathogen in 17 of 22 patients
      (sensitivity: 77%) and in 15 of 15 patients with cytomegalovirus colitis
      (sensitivity: 100%). Combined left and right colonic biopsies had a sensitivity
      of 82%. Combined colonic and terminal ileum biopsies missed no pathogens.
      Duodenal biopsies yielded no additional pathogens beyond those identified by
      colonoscopy and terminal ileal biopsy. Patients with a new pathogen diagnosed had
      significantly lower CD4 lymphocyte counts as compared to patients without a new
      pathogen (p = 0.001). CONCLUSIONS: For patients with CD4 counts < 100/mm3 and
      unexplained AIDS-related diarrhea, flexible sigmoidoscopy with biopsy is a
      sufficiently thorough endoscopic evaluation.

PMID- 10086638
TI  - Transjugular intrahepatic portosystemic shunt (TIPS) for Budd-Chiari syndrome or
      portal vein thrombosis: review of indications and problems.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of transjugular
      intrahepatic portosystemic shunt (TIPS) in patients who present with portal vein
      thrombosis (PVT) or Budd-Chiari Syndrome (BCS). METHODS: Nine patients with
      recent PVT and four patients with BCS underwent TIPS. The diagnosis was confirmed
      by color Doppler ultrasound and by angiogram in most patients. Patients were
      followed clinically and had TIPS checked periodically for patency. The end point
      was mortality, subsequent surgical shunting or orthotopic liver transplantation
      (OLT). RESULTS: TIPS was placed in 13 of 15 (87%) patients with BCS or PVT. The
      mean decrease in pressure gradient was 56%. Median and mean follow-up were 14
      months and 16.9 months. Procedure related complications occurred in two of 13
      (15%), both in the PVT group. Direct procedural mortality was one of 13 (8%). The
      majority of patients with PVT (five of eight) underwent OLT. Of the remaining
      three, one patient subsequently developed a cavernous transformation of portal
      vein but is stable, one patient is stable, without further variceal bleeding, and
      one patient died because of multiple organ failure. In patients with BCS, three
      of four (75%) did well with TIPS, but one patient required immediate surgical
      shunting after occlusion of the TIPS. Two patients underwent OLT and the fourth
      patient is stable 2 yr later but has cirrhosis on biopsy. CONCLUSIONS: In
      patients with BCS, TIPS placement is effective and can be used as a bridge to
      liver transplantation. TIPS in the noncavernous PVT group should only be
      recommended when cirrhosis and uncontrollable variceal bleeding are present.

PMID- 10086639
TI  - Physiology of refractory chronic constipation.
AB  - OBJECTIVE: Investigators suggest three distinct pathophysiologies for patients
      with constipation symptoms: 1) slow colon transit, 2) irritable bowel syndrome
      (IBS), and 3) pelvic floor dysfunction (PFD). Our aim was to determine the
      prevalence of the three types of constipation pathophysiology, the degree of
      overlap, and what interactions exist between pathophysiologies. METHODS:
      Constipated patients refractory to fiber (n = 131) underwent regional colon
      transit studies, anorectal manometry/EMG, measurement of rectal compliance, and
      rectal sensory testing. Correlations were performed examining interactions
      between the above measures. RESULTS: Visceral hypersensitivity (typical of IBS)
      was found in 58%, slow colonic transit in 47%, PFD in 59%, and no physiological
      abnormalities were detected in 24%. Slow transit and visceral hypersensitivity
      overlapped in half of each group. PFD physiology was found in approximately half
      of each of the subgroups. There was no correlation between PFD physiology and
      rectosigmoid transit, total colon transit, or any other physiology. There were no
      correlations between slow transit and visceral hypersensitivity. Visceral
      hypersensitivity did correlate with increased rectal compliance, suggestive of
      increased accommodation reflexes in IBS. CONCLUSIONS: At a tertiary center, slow
      transit physiology and visceral hypersensitivity typical of IBS are equally
      common and overlap heavily in constipated patients. PFD physiology does not
      correlate with slower rectosigmoid colon transit, and is seen equally in all
      subgroups. No abnormalities were found in 24% of patients. We therefore identify
      four subgroups in constipation: IBS, slow transit, both, and neither.

PMID- 10086640
TI  - The impact of open access 24-h pH-metry on the diagnosis and management of
      esophageal reflux disease.
AB  - OBJECTIVE: This study investigates whether the results of 24-h pH-metry can be
      predicted from clinical information and whether they affect patient management.
      METHODS: A total of 200 consecutive patients referred for 24-h pH-metry underwent
      structured interviews as well as endoscopic and manometric investigations. The
      most recent 53 patients were prospectively followed to determine the impact of pH
      monitoring on long term management. RESULTS: Among a variety of risk factors, the
      presence of lower esophageal sphincter hypotension (OR = 3.3) and erosive
      esophagitis (OR = 2.3) were highly predictive of a pathological pH test result.
      If both abnormalities were present, the risk for an abnormal 24-h pH study
      increased by a factor of seven. Twenty-four-hour pH monitoring led to an
      immediate change in management in 42% of all investigated patients. However, such
      alterations in therapy were maintained for prolonged periods in less than half of
      them and only 6% of all patients associated changes in management with an
      improvement of symptoms. CONCLUSIONS: The results of "open access" 24-h pH-metry
      are often predictable, and only a minority of patients benefit from this
      procedure in terms of a change in therapy and an improvement of symptoms.

PMID- 10086641
TI  - Characteristics of intestinal metaplasia in the gastric cardia.
AB  - OBJECTIVE: Intestinal metaplasia of the gastroesophageal junction is frequently
      grouped together with Barrett's esophagus. The area of the gastroesophageal
      junction is comprised of the distal esophagus and the gastric cardia. The aim of
      the present study was to assess whether intestinal metaplasia in the distal
      esophagus and gastric cardia represent two different entities with a different
      set of risk factors. METHODS: Patients presenting for elective upper endoscopy
      were enrolled into a prospective study. The presence of gastritis and intestinal
      metaplasia was evaluated in gastric biopsies taken from the antrum, corpus, and
      cardia. Barrett's esophagus was defined by the presence of any length of columnar
      mucosa above the gastroesophageal junction. RESULTS: Of 302 patients, 50 patients
      had intestinal metaplasia of the gastric cardia, 73 Barrett's esophagus, and 116
      erosive esophagitis. Men were more prone than women to develop Barrett's
      esophagus or erosive esophagitis. Both conditions were also more common among
      whites than nonwhites. Smoking was particularly common among patients with
      Barrett's esophagus. Patients with cardiac intestinal metaplasia did not share
      these demographic characteristics. The prevalence of daily reflux symptoms,
      erosive esophagitis, and Barrett's esophagus was similar among patients both with
      and without cardiac intestinal metaplasia. However, atrophy and intestinal
      metaplasia of the gastric antrum and corpus were found more frequently among
      patients with than without cardiac intestinal metaplasia. CONCLUSIONS: Intestinal
      metaplasia of the gastric cardia is different from Barrett's esophagus. Although
      cardiac intestinal metaplasia is closely associated with signs of gastritis in
      other parts of the stomach, gastroesophageal reflux disease does not seem to be a
      risk factor. A diagnosis of Barrett's esophagus should not be made based on the
      presence of intestinal metaplasia within the cardiac portion of the
      gastroesophageal junction.

PMID- 10086642
TI  - Esophageal hypersensitivity may be a major cause of heartburn.
AB  - OBJECTIVE: Little is known about esophageal nociceptive thresholds in chronic
      heartburn sufferers with normal clinical findings. The aim of this study was to
      evaluate and to characterize the pathogenesis of heartburn in subjects who
      chronically use antacids and had not sought medical attention. METHODS: Subjects
      (N = 152) with chronic heartburn of > or = 3 months duration underwent endoscopic
      grading of the esophagus, esophageal manometry, Bernstein testing,
      intraesophageal balloon distention (IEBD), and 24-h esophageal pH monitoring.
      RESULTS: Normal acid contact time (ACT < or = 6%) was observed in 43% of these
      subjects with recurrent heartburn. Of subjects with normal ACT, 64% had normal
      LES pressure (> or = 10 mm Hg), 79% had normal esophageal endoscopy, 89%
      developed heartburn during Bernstein acid infusion, and 52% perceived IEBD as
      painful. CONCLUSIONS: Approximately 30% of individuals chronically using antacids
      for heartburn had esophageal sensitivity to mechanical or chemical stimuli
      despite negative endoscopy and pH monitoring. Our findings suggest that a
      significant subset of typical heartburn sufferers have a lower threshold for
      esophageal sensation and pain, which may influence options for pharmacological
      intervention in such subjects.

PMID- 10086643
TI  - Laparoscopic antireflux surgery for the treatment of esophageal strictures
      refractory to medical therapy.
AB  - OBJECTIVE: The response of esophageal strictures to laparoscopic antireflux
      surgery remains controversial. The aim of this study was to examine the outcome
      of patients with medically refractory esophageal strictures caused by severe
      gastroesophageal reflux disease and treated surgically. METHODS: A prospective
      follow-up analysis was completed using data obtained from detailed specific
      questioning by an independent observer. Responses were rated for symptoms,
      dysphagia (range 1-19), satisfaction with treatment, well-being (1 = best, 10 =
      worst), and need for further therapy. RESULTS: Of 102 patients, 74 (72.5%)
      responded to follow-up. There were 31 women, mean age 59.6 yr, and 43 men, mean
      age 55.2 yr. Mean follow-up was 25 months (range 4-68 months). A total of 252
      dilations before surgery decreased to 29 after surgery (p < 0.0001) in the mean
      observation period of 26 months before and 25 months after surgery (mean/patient
      5.3 and 1.8, respectively, p < 0.001). The mean dysphagia score was 6.8 +/- 3.6
      preoperatively and 3.7 +/- 1.4 postoperatively (p < 0.0001). Nine (12%) patients
      required continuous postoperative H2-blockers or proton pump inhibitors. Seven of
      these had gastritis or peptic ulcer disease. Before antireflux surgery, 10
      (13.5%) had frequent pneumonia. No pneumonia was observed after surgery. Sixty
      eight (91.9%) patients were satisfied with their decision to have surgery. Among
      these, the well-being score was 1.8 +/- 0.4 postoperatively vs 5.5 +/- 1.2 (p <
      0.001) preoperatively. CONCLUSIONS: Laparoscopic surgery in patients with
      medically refractory esophageal strictures results in a good clinical outcome
      with minimal complications. Patients are very satisfied with relief of dysphagia,
      and there is a diminished need for further dilation, with good quality of life.

PMID- 10086644
TI  - Use of botulinum toxin as a diagnostic/therapeutic trial to help clarify an
      indication for definitive therapy in patients with achalasia.
AB  - OBJECTIVE: Intrasphincteric injection of botulinum toxin is useful in achalasia
      but is limited by its short term efficacy. The aim of this study was to evaluate
      the use of botulinum toxin in selected patients in whom its short duration of
      action may be useful in guiding therapy before considering more invasive
      procedures that might not be indicated. METHODS: Over a 3 yr period, botulinum
      toxin was injected into the lower esophageal sphincter in patients with: 1)
      symptoms consistent with achalasia but insufficient manometric criteria to make
      the diagnosis; 2) complex clinical situations in which there were factors in
      addition to achalasia that may be contributing to the patient's symptoms and that
      required different treatment; 3) atypical manifestations of achalasia; 4)
      advanced achalasia in which it was unclear that sphincter-directed therapy (vs
      esophagectomy) would be of benefit; and 5) after Heller myotomy. Clinical
      response was assessed mostly by symptom improvement, but in some patients follow
      up barium swallow or radioscintigraphy was available. RESULTS: Eleven patients
      were identified. Ten had complete symptomatic response to the injection. Two
      patients have undergone subsequent successful pneumatic dilation, one a
      successful laparoscopic myotomy, and another currently scheduled for surgical
      myotomy. The only patient without response had advanced achalasia requiring
      esophagectomy. CONCLUSIONS: Intrasphincteric injection of botulinum toxin into
      the lower esophageal sphincter is a useful and safe means of guiding therapy in
      those patients with a variant of achalasia, atypical achalasia, or complex
      achalasia in which it is unclear that more invasive procedures such as pneumatic
      dilation or surgical myotomy are the correct therapy.

PMID- 10086645
TI  - Balloon-occluded retrograde transvenous obliteration of high risk gastric fundal
      varices.
AB  - OBJECTIVE: Balloon-occluded retrograde transvenous obliteration is an effective
      new method for treating gastric fundal varices, but subsequent occurrence of
      esophageal varices creates a problem. The relationship between portal
      hemodynamics and the occurrence of esophageal varices after prophylactic balloon
      occluded retrograde transvenous obliteration was investigated. METHODS: Ten
      cirrhotic patients considered to have high risk gastric fundal varices underwent
      angiography. Six patients showed a communication between blood flow in gastric
      wall vessels and that in the gastrorenal shunt (type I), whereas the others (type
      II) did not. Depending on the flow direction in the left gastric vein, the two
      groups were further divided into hepatopetal (a) and hepatofugal (b) subgroups.
      The therapeutic effect on portal hemodynamics and the relationship between
      pretreatment portal hemodynamics and posttreatment occurrence of esophageal
      varices were investigated. RESULTS: Fundal varices disappeared endoscopically in
      all 10 patients and the gastrorenal shunt was also occluded after the procedure.
      No patient showed worsening of liver function or systemic complications during
      follow-up. The increase in portal blood flow was more significant in type Ib
      patients than in the others. Esophageal varices occurred in all type I patients,
      and as to those in type Ib, high risk varices developed within 6 months after
      treatment. On the other hand, esophageal varices did not occur in type II
      patients. CONCLUSIONS: This procedure was effective for treating gastric fundal
      varices. However, type Ib patients are likely to develop high risk esophageal
      varices after occlusion of the gastrorenal shunt.

PMID- 10086646
TI  - Serum des-gamma-carboxy prothrombin levels determined by a new generation of
      sensitive immunoassays in patients with small-sized hepatocellular carcinoma.
AB  - OBJECTIVE: Des-gamma-carboxy prothrombin (DCP), also called protein induced by
      vitamin K absence or antagonist II (PIVKA-II), is a tumor marker complementary to
      AFP for the diagnosis of hepatocellular carcinoma (HCC). Currently available
      immunoassays for DCP are not sensitive enough to detect HCC at an early stage.
      Recently, two new immunoassays with enhanced sensitivity were developed. The aim
      of this study was to assess the diagnostic values of the new methods in patients
      with small-sized HCC. METHODS: Coded serum samples obtained from 36 patients with
      small-sized and single-nodular HCC (< or = 3 cm in diameter) and 49 patients with
      posthepatitic cirrhosis not carrying HCC were analyzed. DCP levels were
      determined in three different ways: 1) conventional EIA; 2) a new immunoassay
      using the electrochemiluminescence (ECLIA) detection system; and 3) a new
      immunoradiometric assay (IRMA). Lectin-reactive profiles of AFP (AFP-L3) were
      also determined. RESULTS: In 36 patients with small-sized HCC, the rates of
      abnormal values obtained by the conventional, ECLIA, and IRMA methods were 2.7%,
      27.8%, and 16.7%, respectively. An ROC analysis of the two new methods (ECLIA vs
      IRMA) revealed a better performance by the ECLIA method (p < 0.05). The true
      positive rate of AFP-L3 was 22.2%, whereas a combination assay of ECLIA for DCP
      and AFP-L3 resulted in a 41.7% sensitivity with a specificity of 90%.
      CONCLUSIONS: Compared with the conventional method, the sensitivity in detecting
      small-sized HCC was increased in the two new DCP immunoassays (ECLIA and IRMA).
      The overall performance as evaluated by an ROC analysis was significantly better
      in ECLIA than in IRMA.

PMID- 10086647
TI  - Cardiovascular disease in cirrhosis--a point-prevalence study in relation to
      glucose tolerance.
AB  - OBJECTIVE: Impaired glucose tolerance or diabetes are frequently observed in
      cirrhosis. Overt diabetes was reported to affect long term survival of cirrhotic
      patients by increasing the risk of hepatocellular failure, without increasing the
      risk of diabetes-associated cardiovascular events. METHODS: We evaluated the
      prevalence of cardiovascular disease in 122 patients with cirrhosis, subdivided
      according to their glucose tolerance. The following parameters were considered:
      arterial pressure, peripheral vascular disease (ankle to brachial pressure
      ratio), ischemic heart disease, microalbuminuria, retinopathy. The prevalence of
      abnormal findings was compared with that observed in 60 randomly selected
      patients with noninsulin-dependent diabetes and in 40 controls. RESULTS:
      Noninsulin-dependent diabetic patients and patients with cirrhosis and diabetes
      were comparable for age, metabolic control, and smoking habits; the duration of
      diabetes was 5 yr longer for noninsulin-dependent diabetes. In cirrhosis, the
      prevalence of micro- and peripheral macroangiopathy, as well as coronary heart
      disease, was not different in relation to glucose tolerance, it was comparable to
      that of controls, and significantly lower than that observed in non-insulin
      dependent diabetes. CONCLUSIONS: Cirrhotic patients, even in the presence of
      overt diabetes, are at low risk of cardiovascular disease. The low prevalence may
      be related to shorter duration of diabetic disease, also in relation to reduced
      life expectancy, as well as to liver disease-induced abnormalities protecting the
      cardiovascular system from atherosclerosis.

PMID- 10086648
TI  - Efficacy of lamivudine in patients with hepatitis B virus precore mutant
      infection before and after liver transplantation.
AB  - OBJECTIVE: Hepatitis B virus (HBV) precore mutant infection is associated with a
      more severe liver disease and a poorer response to interferon. We evaluated the
      efficacy and tolerance of lamivudine to induce complete and sustained suppression
      of viral replication in seven patients infected with HBV precore mutant (HBeAg
      /HBeAb+/HBV DNA+) (in three patients mutation at codon 1896 was detected by
      direct sequencing). METHODS: Of the seven patients, five had decompensated HBV
      cirrhosis in a replicative phase and were liver transplant candidates (Group A)
      and two patients underwent orthotopic liver transplantation (OLT) for HBV liver
      cirrhosis and developed recurrent HBV infection in the grafted liver (Group B).
      Lamivudine 100 mg daily was administered orally for a period of 6-75 wk. RESULTS:
      After 6-8 wk lamivudine therapy was well tolerated and successfully suppressed
      HBV replication to an undetectable serum level of HBV DNA by polymerase chain
      reaction in six patients. In Group A, two patients underwent successful OLT with
      no evidence of HBV reinfection 2-14 months later. Lamivudine was continued after
      OLT with no episodes of rejection. Three patients died before a suitable liver
      could be found (one remained serum HBV DNA+ after 6 wk of lamivudine therapy). In
      Group B, 9-14 months after lamivudine therapy both patients developed lamivudine
      resistance (increased liver enzymes, reappearance of serum HBsAg and HBV DNA [by
      hybridization]). In both patients liver histology had progressed and in both,
      mutation at codon 552 of the HBV polymerase gene was detected. CONCLUSIONS:
      Lamivudine is well tolerated in patients with decompensated liver cirrhosis due
      to HBV precore mutant infection who are liver transplant candidates. In four
      patients (80%) potent suppression of viral replication was detected, allowing OLT
      to be performed. However, post-OLT, a resistant mutant developed under lamivudine
      therapy. Combination therapy with other antiviral agents should be evaluated to
      discourage the emergence of lamivudine-resistant mutants.

PMID- 10086649
TI  - A case-control study of the factors associated with spontaneous resolution of
      hepatitis C viremia.
AB  - OBJECTIVE: Infection with the hepatitis C virus (HCV) becomes chronic in 85% of
      the infected individuals. We studied risk factors that may predict clearance of
      HCV. METHODS: A case-control study compared the association between risk factors
      and viral clearance. Viral clearance was defined as presence of a positive HCV
      antibody test plus negative HCV test by polymerase chain reaction (PCR). Forty
      four cases and 214 controls with persistent viremia were identified in a database
      of patients evaluated at the Gastroenterology Clinic of the University of New
      Mexico. RESULTS: Of all 258 HCV-antibody-positive patients, 17% had a negative
      test by PCR. The multivariate logistic regression revealed that a history of
      parenteral exposure and a long time interval since the most recent exposure were
      both associated with an increased likelihood of persistent viremia, whereas
      subjects who had been monogamous for longer time periods were more likely to have
      cleared HCV from their serum. A low serum level of ferritin also conferred
      protection against persistent viremia. Case and control subjects did not differ
      with respect to their demographic characteristics, occurrence of comorbid
      disease, previous medical history, occurrence of sexually transmitted diseases,
      blood group, and risky health or sexual practices. CONCLUSIONS: These data
      suggest that route of exposure and time when exposure occurred are important in
      the development of persistent HCV infection.

PMID- 10086650
TI  - A controlled trial comparing ciprofloxacin with mesalazine for the treatment of
      active Crohn's disease. Groupe d'Etudes Therapeutiques des Affections
      Inflammatoires Digestives (GETAID).
AB  - OBJECTIVE: The aim of this randomized controlled study was to investigate the
      efficacy of ciprofloxacin compared with mesalazine in treating active Crohn's
      disease. METHODS: Patients with a mild to moderate flare-up of Crohn's disease
      (mean Crohn's Disease Activity Index [CDAI]; 217; range, 160-305) were randomized
      to receive ciprofloxacin 1 g/day or Pentasa 4 g/day for 6 wk. Complete remission
      was defined at wk 6 as a CDAI < or = 150 associated with a decrease (delta) in
      CDAI > 75. Partial remission was defined as a CDAI < or = 150 with 50 < delta
      CDAI < 75 or a CDAI > 150 with delta CDAI > 50 at wk 6. Group sequential
      procedure with triangular continuation regions was used to monitor the trial
      through the difference in complete remission rates, every 20 patients included.
      RESULTS: Inclusion of patients was stopped at the second step, i.e., after 40
      inclusions, with the conclusion of no difference in complete remission rates
      between ciprofloxacin- and Pentasa-treated groups. Among the 18 patients taking
      ciprofloxacin, two decided to stop treatment during the trial and three were
      considered as treatment failures because of deterioration at wk 3. Among the 22
      patients taking mesalazine, one patient was lost to follow-up and eight patients
      were considered as treatment failures. Complete remission was observed in 10
      patients (56%) treated with ciprofloxacin and 12 patients (55%) treated with
      mesalazine and partial remission was observed in three and one patient,
      respectively. CONCLUSIONS: This study suggests that ciprofloxacin 1 g/day is as
      effective as mesalazine 4 g/day in treating mild to moderate flare-up of Crohn's
      disease.

PMID- 10086651
TI  - Exposure to risk factors for ulcerative colitis occurs during an early period of
      life.
AB  - OBJECTIVE: It has been speculated that environmental factors play a role in the
      etiology of ulcerative colitis. A previous analysis revealed that the time trends
      of ulcerative colitis in England were shaped by an underlying birth-cohort
      pattern. We undertook this study to test whether the birth-cohort pattern was a
      unique feature of the English vital statistics or whether a similar phenomenon
      could also be ascertained in the mortality statistics from a different country,
      such as Switzerland. Besides comparing the data of ulcerative colitis from
      Switzerland and England, the trends of ulcerative colitis were compared with
      those of gastric and duodenal ulcer. METHODS: Death rates from ulcerative
      colitis, gastric ulcer, and duodenal ulcer were plotted against the period of
      death and period of birth. An age-standardized cohort mortality ratio was
      calculated as a summary statistic of the overall mortality associated with each
      consecutive birth-cohort. RESULTS: Mortality from ulcerative colitis increased
      among successive generations born throughout the 19th century. It peaked in
      individuals born around 1890 and has declined since then. Strikingly similar
      patterns were found in Switzerland and England. The birth-cohort pattern
      underlying the time trends of ulcerative colitis applied equally to the data for
      women and men. In comparison with peptic ulcer, the birth-cohort pattern of
      ulcerative colitis was almost identical to that of duodenal ulcer. It peaked in
      both countries 10-20 yr later than gastric ulcer. CONCLUSIONS: The birth-cohort
      pattern indicates that acquisition of ulcerative colitis is strongly influenced
      by environmental risk factors and that the exposure to these factors occurs
      during an early period of life. The similarity in the birth-cohort patterns of
      duodenal ulcer and ulcerative colitis could hint at a childhood infection or a
      related mode of transmission in both diseases.

PMID- 10086652
TI  - Thromboembolism and resistance to activated protein C in patients with
      inflammatory bowel disease.
AB  - OBJECTIVE: Thromboembolic events are serious complications in patients with
      inflammatory bowel disease (IBD). Resistance of factor V to degradation by
      activated protein C (APC) is a major cause for venous thrombosis and is found in
      approximately 30% of patients with thromboembolism. The aim of the present study
      was to assess the prevalence of APC resistance and clinical risk factors in
      patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38
      men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with
      ulcerative colitis) and 102 gender- and age-matched healthy control subjects were
      investigated prospectively for the presence of APC resistance. None of the
      healthy controls but 16 patients with IBD had a history of thromboembolism.
      RESULTS: Patients with IBD and thromboembolism were young, with a median age of
      37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more
      common than in patients with IBD without thromboembolism (7%) and in controls
      (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13
      each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most
      common thromboembolic complications (84.2%). Active disease, fistula, or bowel
      stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%)
      cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is
      not associated with IBD but, when present, increases the risk of thromboembolism.
      Patients with IBD and thromboembolism are mostly young and clinical risk factors
      can be found in one-half of cases.

PMID- 10086653
TI  - The clinical pattern of subclinical/silent celiac disease: an analysis on 1026
      consecutive cases.
AB  - OBJECTIVE: The demographic, clinical, and epidemiological features of
      subclinical/silent celiac disease in Italy were analyzed in a multicenter study
      carried out with the participation of 42 centers, in the years between 1990 and
      1994. METHODS: One thousand twenty-six subclinical/silent patients (644 children
      and 382 adults, 702 women and 324 men) were considered eligible for the study.
      RESULTS: The prevalence of the subclinical/silent form increased significantly
      during the study both in adults (p < 0.001) and in children (p < 0.005), but its
      prevalence was always lower (p < 0.001) in children than in adults. This increase
      appears more likely due to a greater diagnostic awareness and to a better use of
      screening than to a higher number of subclinical/silent cases. Whereas in 1990 a
      significantly higher proportion (p < 0.001) of subclinical/silent celiac patients
      was diagnosed in Northern Italy rather than in Southern-Insular Italy, both in
      adults (46.7% vs 17.2%) and in children (22.0% vs 9.0%), in 1994 such a
      difference was no longer conspicuous. Both in children and in adults, iron
      deficiency anemia appeared to be the most frequent extraintestinal symptom,
      followed by short stature in children and cutaneous lesions of dermatitis
      herpetiformis in adults. In 25.9% of the cases another disease was present, with
      a significantly higher frequency (p < 0.05) in adults (30.1%) than in children
      (20.7%). Diabetes and atopy appeared to be the most frequently associated
      conditions both in children and in adults. CONCLUSIONS: This study has provided
      an analysis of the largest series of subclinical/silent celiac disease reported
      to date. In Italy, this form is most frequently recognized in adults, and
      prospective studies will clarify whether the lower frequency observed in children
      is a real or apparent phenomenon.

PMID- 10086654
TI  - The effects of physical exercise on patients with Crohn's disease.
AB  - OBJECTIVE: Despite the suggested benefits of exercise training in the prevention
      and management of chronic diseases, few data exist regarding the safety of
      exercise in Crohn's disease and whether or not exercise may have beneficial
      effects on patients' health. We performed a pilot study to evaluate the effects
      of regular light-intensity exercise on sedentary patients with Crohn's disease.
      METHODS: Sedentary patients with inactive or mildly active Crohn's disease were
      eligible for the study. A thrice-weekly, 12-wk walking program was supervised,
      although if subjects could not attend the group walking sessions they were
      allowed to walk on their own. Logbooks of performance were maintained, and
      individual exercise heart rate goals were established. Measures performed at
      baseline and at study completion included the Inflammatory Bowel Disease Stress
      Index, the Inflammatory Bowel Disease Quality of Life Score, the Harvey and
      Bradshaw Simple Index, the Canadian Aerobic Fitness Test, VO2 Max, and body mass
      index (BMI). RESULTS: Twelve subjects completed the 12-wk exercise program.
      Subjects walked an average of 2.9 sessions/wk, at an average of 32.6 min/session,
      and for an average distance of 3.5 km/session. Statistically significant
      improvements at study end were seen by all measures, with a trend toward
      reduction in BMI. No patient's disease flared during the study. CONCLUSIONS:
      Sedentary patients with Crohn's disease can tolerate low-intensity exercise of
      moderate duration without an exacerbation of symptoms. Twelve weeks of walking
      was adequate to elicit psychological and physical improvements and did not
      adversely affect disease activity.

PMID- 10086655
TI  - Increased interleukin-8 (IL-8) in rectal dialysate from patients with ulcerative
      colitis: evidence for a biological role for IL-8 in inflammation of the colon.
AB  - OBJECTIVE: Infiltration of neutrophils and their release of toxic reactive oxygen
      species (ROS) in the colonic mucosa are associated with tissue damage in
      ulcerative colitis (UC). This neutrophil migration may be induced by
      chemoattractants, such as cytokines, in the colonic milieu. One such
      chemoattractant is interleukin-8 (IL-8), a neutrophil chemokine that is present
      at high concentrations in inflamed mucosa. However, the functional significance
      of IL-8 in neutrophil attraction and activation in UC has not been established.
      We hypothesized that IL-8 in the colonic lumen of patients with UC primes
      neutrophils, leading to their attraction and activation. METHODS: The colonic
      milieu was sampled by rectal dialysis. Using a semi-permeable membrane with a
      molecular weight cut-off of 12 kDa, dialysis solution was placed in the rectum
      and allowed to equilibrate over a 4-h period with the colonic milieu of controls
      or of patients with UC. IL-8 concentrations were measured by ELISA. Two functions
      of healthy neutrophils (PMN) were measured: expression of CD11-b surface adhesion
      molecules (by flow cytometry), and production of ROS (by both chemiluminescence
      and cytochrome C reduction assays). Neutrophil functions after exposure to rectal
      dialysates or n-formyl-methionyl-leucyl-phenylalanine (fMLP) were assessed before
      and after adding anti-IL-8 antibody or the fMLP blocker BMLP. RESULTS: IL-8
      concentrations in dialysates from patients with active UC were significantly
      higher than in controls and correlated with disease activity. UC dialysates
      significantly increased ROS production and CD11-b expression by neutrophils and
      anti-IL-8 antibody partially (50%) inhibited these stimulatory effects of UC
      dialysates. Preincubation of neutrophils with UC dialysates significantly
      potentiated the fMLP-induced rise in ROS and anti-IL-8 antibody completely
      abolished this priming effect. CONCLUSIONS: The colonic milieu, sampled by rectal
      dialysis, from patients with active UC can both activate and prime neutrophils in
      vitro. High concentrations of IL-8 in the colonic lumen of UC patients are
      partially responsible for the activating effects of rectal dialysates, and
      account for all of its priming effects. These findings provide direct evidence
      for a role for IL-8 in inflammatory bowel disease.

PMID- 10086656
TI  - Gene expression of group II phospholipase A2 in intestine in Crohn's disease.
AB  - OBJECTIVE: Phospholipase A2 (PLA2) has been suggested to play an important role
      in the pathogenesis of inflammatory bowel diseases. Our aim was to identify cells
      that express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein
      levels in the intestine in Crohn's disease. METHODS: Tissue samples were obtained
      from the intestine of 20 patients with Crohn's disease (seven operated and 13
      colonoscopied) and from eight control patients without inflammatory diseases. The
      samples were studied by immunohistochemistry for PLA2-II enzyme protein and in
      situ hybridization for PLA2-II mRNA. RESULTS: PLA2-II protein and mRNA were
      detected in the Paneth cells of the small intestinal mucosa in all patients and
      controls. PLA2-II protein and mRNA were found in the columnar epithelial cells of
      the small intestinal mucosa in six of eight and eight of eight patients with
      Crohn's ileitis, respectively. In the eight control patients PLA2-II protein and
      mRNA were not found in these cells (p = 0.007 and p < 0.001, respectively).
      Metaplastic Paneth cells, which consistently contained PLA2-II mRNA, were found
      in the colonic mucosa in five of six patients with Crohn's colitis and of one of
      eight control patients (p = 0.026). The columnar epithelial cells of the colonic
      mucosa contained PLA2-II protein in three of six and PLA2-II mRNA in six of six
      patients with Crohn's colitis, whereas the protein was found in these cells in
      none of eight of the controls (p = 0.055) and the mRNA in only one of eight (p =
      0.005) controls. CONCLUSIONS: In Crohn's disease, Paneth cells and columnar
      epithelial cells of the small and large intestinal mucosa synthesize PLA2-II at
      the site of active inflammation.

PMID- 10086657
TI  - One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based
      anti-Helicobacter triple therapy: a prospective randomized controlled trial.
AB  - OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by
      the presence of metronidazole resistance. In vitro studies suggest that
      ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity
      against metronidazole resistant strains of Helicobacter pylori (H. pylori).
      Whether this confers a superior clinical efficacy remains unproven. This study
      compared the efficacy of RBC-based triple therapy with bismuth triple therapy in
      eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease
      or gastritis were randomized to receive either 400/mg of RBC twice daily plus
      400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk
      (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and
      500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole
      susceptibility was determined by the E-test and pretreatment resistance was
      defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100
      consecutive patients randomized, two patients were lost to follow-up in each
      group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant.
      Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%),
      respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50
      and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher
      eradication of metronidazole resistant H. pylori was observed in the RMT group
      (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects
      observed in the two treatment groups were comparable. CONCLUSIONS: One week of
      RBC triple therapy with metronidazole and tetracycline is an effective anti
      Helicobacter therapy. This regimen is more appropriate in areas of high
      prevalence of metronidazole resistance.

PMID- 10086658
TI  - Costs of diagnosis and treatment of Helicobacter pylori infection: when does
      choosing the treatment regimen based on susceptibility testing become cost
      effective?
AB  - OBJECTIVE: Antibiotic-resistant Helicobacter pylori (H. pylori) strains are
      becoming increasingly prevalent. Currently, most physicians treat H. pylori
      infections without relying on antimicrobial susceptibility testing to choose the
      best regimen. This study was conducted to evaluate whether routine pretreatment
      susceptibility testing is cost effective from a third party payer point of view.
      METHODS: A decision model was devised to compare direct costs and outcome for
      diagnosis and treatment over 1 year for two different strategies. Strategy A:
      Endoscopy plus biopsy followed by an empirical antibiotic treatment of H. pylori
      positive ulcer patients. Treatment failure was followed by reendoscopy with
      biopsy and antibiotic susceptibility testing and a second treatment. Strategy B:
      Endoscopy as in strategy A now followed by antibiotic susceptibility testing and
      tailored antibiotic treatment. Treatment failure was handled as in strategy A.
      RESULTS: Following through with strategy A or B, the overall cure rate for both
      strategies was virtually identical. Therefore, cost effectiveness is defined as
      money saved per patient by using strategy B, while achieving similar
      effectiveness (cure rates). As an example we compared therapies for a population
      with known parameters for antibiotic resistance as well as cure rates.
      Pretreatment susceptibility testing would save $37,000 per 1,000 patients
      treated. According to our model (equal therapy-price assumption in strategy A and
      B), pretreatment susceptibility testing for metronidazole is less costly for all
      the reported populations worldwide. CONCLUSIONS: Our decision analysis suggests
      that routine pretreatment susceptibility testing can be cost effective under
      various settings. The model presented is easily transferable to any population as
      long as the following variables are known: 1) the proportion of H. pylori strains
      in the population that are resistant to the antibiotics of the initial regimen;
      2) the cure rate in sensitive H. pylori strains; 3) the cure rate in resistant H.
      pylori strains; and 4) the costs for diagnosis and treatment used.

PMID- 10086659
TI  - Measuring quality of life in dyspeptic patients: development and validation of a
      new specific health status questionnaire: final report from the Italian QPD
      project involving 4000 patients.
AB  - OBJECTIVE: Despite the fact that gastrointestinal disorders represent one of the
      most common reasons for medical consultations, formal assessment of patients'
      health-related quality of life (HRQOL) has been carried out only in a few
      studies, and in most cases generic questionnaires have been adopted. Because the
      specific issue of living with dyspeptic problems has been addressed in very few
      cases and no questionnaire has been shown to be appropriate for the Italian
      setting, a prospective project was launched to develop a specific HRQOL
      questionnaire for dyspepsia sufferers tailored to Italian patients but also
      appropriate in other cultural settings. METHODS: The project consisted in a 3-yr,
      three-phase survey, in which different versions of the quality of life in peptic
      disease questionnaire (QPD) were developed through expert and patient focus
      groups and empiric field studies and then administered to patients recruited in
      five multicenter studies. Standard psychometric techniques were used to evaluate
      the validity, reliability, responsiveness, and patient acceptability of the QPD.
      RESULTS: Three different versions of the QPD questionnaire were self-administered
      to more than 4000 patients. The final 30-item version, measuring three health
      concepts related to dyspeptic disease (anxiety induced by pain, social
      restriction, symptom perception), fulfilled the recommended psychometric criteria
      in terms of reliability and validity, correlated with health concepts measured
      with a well-known independent generic HRQOL instrument (the SF-36 Health Survey
      questionnaire) and was relatively invariant to diagnosis and sociodemographic
      variables; it also correlated with a measure of gastric pain frequency and was
      able to detect meaningful differences over time. CONCLUSIONS: Although further
      validation studies in different cultural and linguistic settings are mandatory
      before any firm conclusions can be drawn regarding the cross-cultural validity of
      the QPD, the data obtained provide evidence of the psychometric validity and
      robustness of the questionnaire when used in a fairly large, well-characterized
      population of Italian dyspeptic patients.

PMID- 10086660
TI  - Histopathological prognostic factors influencing long-term prognosis after
      surgical resection for hepatic metastases from colorectal cancer.
AB  - OBJECTIVE: We aimed to present new histopathological features of metastatic liver
      nodules as more reliable prognostic factors after surgical resection for
      colorectal metastatic cancer. METHODS: Clinicopathological features, including
      newly proposed histopathological ones, of 63 consecutive patients were reviewed
      retrospectively to determine which most strongly correlated with long-term
      prognosis after hepatectomy for metastatic tumors from colorectal cancers, using
      univariate and multivariate analysis. RESULTS: The 1-, 3-, and 5-year cancer
      related survival rates after hepatectomy were 87.8%, 55.2%, and 47.3%,
      respectively. New histopathological features we proposed, which are expansive
      growth, marginal fibrosis, and peritumorous lymphocytic infiltration of hepatic
      tumor, were significant prognostic factors for cancer-related survival after
      hepatectomy in an univariate analysis. Also in a multivariate analysis, i.e., a
      stepwise Cox regression analysis, infiltrative, i.e., not expansive, growth of
      hepatic tumor was one of significant and independent poor prognostic factors for
      survival after hepatectomy, with moderate to severe lymphatic vessel involvement
      of the primary colorectal lesion, microscopic cancer invasion at the surgical
      margin of hepatectomy, and extrahepatic distant metastases. CONCLUSIONS: Our
      results suggest that our proposed new histopathological features of hepatic
      metastases were good predictors of prognosis after surgical resection for hepatic
      metastases from colorectal cancer. Especially, infiltrative growth of hepatic
      tumor is strongly correlated with a poor prognosis after hepatectomy.

PMID- 10086661
TI  - Lectin binding to human colonocytes is predictive of colonic neoplasia.
AB  - OBJECTIVE: The aim of this study was to determine whether lectin binding to
      exfoliated human colonocytes could be used as a noninvasive test for colorectal
      polyps or cancer. METHODS: Colonocytes were harvested from 31 patients (10
      controls, 10 with adenomatous polyps, and 11 with cancer), incubated with a panel
      of fluorescent-labeled lectins, and assayed by flow cytometry. RESULTS: The
      lectins jacalin (JAC) and wheat germ agglutinin (WGA) were useful in predicting
      the presence of a colorectal neoplasm (p = 0.0018 for JAC and p = 0.0099 for
      WGA). For JAC, sensitivity reached 81% with a specificity of 80%, and for WGA the
      sensitivity and specificity were both 75%. CONCLUSIONS: Lectin binding to human
      colonocytes can predict the presence of malignant and premalignant lesions of the
      colon, and has potential as a noninvasive screening tool for colorectal
      neoplasms.

PMID- 10086662
TI  - The effects of biofeedback on rectal sensation and distal colonic motility in
      patients with disorders of rectal evacuation: evidence of an inhibitory
      rectocolonic reflex in humans?
AB  - OBJECTIVE: Abnormalities of descending colon motility reported in a subset of
      patients with rectal evacuation disorders are consistent with a rectocolonic
      inhibitory reflex. Our aims were to evaluate distal colon motor function and
      rectal sensation in such patients and assess effects of biofeedback (BF) training
      on these functions. METHODS: Seven patients (five women, two men; mean age 36 yr)
      with rectal evacuation disorders were studied before and after 10-days
      biofeedback training; six healthy volunteers (five women, one man; mean age 30
      yr) were studied once. Colonic compliance, motility, sensation thresholds, and
      perception scores during standardized rectal distentions were measured using two
      barostat-manometry assemblies inserted into the cleansed colon with the aid of
      flexible sigmoidoscopy. RESULTS: Sigmoid compliance, fasting, and postprandial
      motility index, and perception thresholds were similar in controls and patients
      before and after biofeedback training. Postprandial sigmoid tone tended (p =
      0.09) to be lower in patients than controls; after biofeedback, postprandial tone
      was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention
      were greater in patients than in controls (p = 0.02 for both). After biofeedback,
      there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm
      pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12
      mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05).
      CONCLUSIONS: Normalization of rectal evacuation and postprandial sigmoid tone in
      patients with evacuation disorders by biofeedback training supports the presence
      of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in
      these patients requires further study.

PMID- 10086663
TI  - Prognostic significance of perioperative blood transfusions in resectable
      thoracic esophageal cancer.
AB  - OBJECTIVE: The perioperative blood transfusions have been associated with tumor
      recurrence and decreased survival in various types of alimentary tract cancer.
      There exist, however, contradictory studies showing no relationship between blood
      transfusions and survival. For patients with esophageal cancer, only one report
      suggested that blood transfusions did not by itself decrease the chance of cure
      after esophagectomy. METHODS: Among 235 patients with primary squamous cell
      carcinoma of the thoracic esophagus between December 1979 and March 1998, 143
      patients (60.9%) underwent esophagectomy with curative intent (RO). To exclude
      the effects of surgery-related postoperative complications, 14 patients who died
      within 90 days during the hospital stay were excluded. Thus, clinicopathological
      characteristics and prognostic factors were retrospectively investigated between
      patients with no or few transfusions (< or = 2 units) (n = 58), and much
      transfused patients (> or = 3 units) (n = 71). RESULTS: Sixty-three patients are
      alive and free of cancer, and 66 patients are dead. A total of 98 patients (76%)
      received blood transfusions, whereas 31 patients (24%) had no transfusion. The
      amount of blood transfused was 1 or 2 units in 27 patients (27.6%), 3 or 4 units
      in 33 (33.7%), 5 or 6 units in 20 (20.4%), and > or = 7 units in 18 (18.4%). The
      5-yr survival rate for patients with no or few transfusions was 69%, whereas that
      for much transfused patients was 31.7% (p < 0.0001). The much transfused patients
      had more prominent ulcerative tumor, longer time of operation, more estimated
      blood loss, and more marked blood vessel invasion than the group with no or few
      transfusions. The factors influencing survival rate were tumor location, Borrmann
      classification, size of tumor, depth of invasion, number of lymph node
      metastases, time of operation, amount of blood transfusions, lymph vessel
      invasion, and blood vessel invasion. Among those nine significant variables
      verified by univariate analysis, independent prognostic factors for survival
      determined by multivariate analysis were number of lymph node metastasis (0 or 1
      vs > or = 2, p < 0.0001), amount of blood transfusions (< or = 2 units vs > or =
      3 units, p < 0.0001), and blood vessel invasion (marked vs non-marked, p =
      0.0207). CONCLUSIONS: There is an association between high amount of blood
      transfusions and decreased survival for patients with resectable esophageal
      cancer. To improve the prognosis, surgeons must be careful to reduce blood loss
      during esophagectomy with extensive lymph node dissection and subsequently must
      minimize blood transfusions.

PMID- 10086664
TI  - High prevalence of atrophic body gastritis in patients with unexplained
      microcytic and macrocytic anemia: a prospective screening study.
AB  - OBJECTIVE: Atrophic body gastritis (ABG) is characterized by atrophy of the
      gastric body mucosa, hypergastrinemia, and hypo/achlorhydria. Its association
      with pernicious anemia is well recognized. Gastric hypo/achlorhydria is known to
      affect iron absorption but ABG is rarely considered as a possible cause of iron
      deficiency (microcytic) anemia. The aims of this study were to validate a
      screening methodology for the detection of ABG in a consecutive series of
      patients with microcytic and macrocytic anemia and to investigate the clinical
      and gastric morphofunctional characteristics of the two hematological
      presentations of ABG. METHODS: A two-part prospective study was carried out. Part
      A aimed to validate the screening methodology to detect the presence of ABG in
      patients with macrocytic and microcytic anemia who have no specific GI symptoms,
      by measuring their gastrin levels and verified by performing gastroscopy with
      biopsy. Part B aimed to detect the presence of ABG in a larger sample of anemic
      patients by our validated method and, by pooling the data of ABG patients, to
      determine the clinical, gastric histological, and functional characteristics
      pertaining to the macrocytic and microcytic presentations of ABG. RESULTS: In
      part A, ABG was detected in 37.5% of patients with macrocytic and in 19.5% of
      those with microcytic anemia. Pooling the data of the ABG patients from part A
      and part B, microcytic ABG patients were on average 20 yr younger than those with
      macrocytic anemia. The majority of microcytic ABG patients were female, most of
      whom were premenopausal. H. pylori infection was widely represented in the
      microcytic ABG group (61.1%). They also had a lesser grade of body mucosal
      atrophy and lower hypergastrinemia levels, suggesting a less severe oxyntic
      damage of shorter duration. CONCLUSIONS: Macrocytic anemia is not the only
      hematological presentation of ABG. Physicians evaluating patients with
      unexplained iron deficiency anemia should consider ABG as a possible cause by
      determining fasting gastrin levels and performing gastroscopy with biopsies of
      the body mucosa.

PMID- 10086665
TI  - Manometric tests of anorectal function in healthy adults.
AB  - OBJECTIVE: Although tests of anorectal function are useful in the assessment of
      defecation disorders, there is inadequate and inconsistent information regarding
      normative data. Also, there are discrepancies in manometric techniques and data
      interpretation. Our aim was to perform a comprehensive evaluation of anorectal
      function in healthy adults. METHODS: We used a 6-mm diameter probe containing six
      radially arrayed microtransducers, and a 4-cm-long latex balloon for performing
      anorectal manometry in 45 healthy subjects who were controlled for gender and
      age. Sequentially, subjects were asked to squeeze, bear down, or blow up a party
      balloon. Subsequently, rectal sensation, rectal compliance, and rectoanal
      reflexes were assessed simultaneously by performing intermittent phasic balloon
      distentions. Additionally, balloon defecation, pudendal nerve latency, and saline
      continence tests were performed. RESULTS: In men, the anal sphincter was longer
      (p < 0.05) and squeeze sphincter pressure and squeeze duration were higher (p <
      0.01), but resting sphincter pressure was similar to that in women. When bearing
      down, although not significant, the defecation index was higher in men. Distinct
      thresholds for rectal sensation were identified but there was no gender
      difference. Likewise, rectal compliance and balloon expulsion time were similar.
      However, during saline infusion, the onset of first leak and total volume
      retained were higher (p < 0.001) and pudendal nerve latency was shorter (p <
      0.05) in men. Overall, parity or age did not influence anorectal function.
      CONCLUSIONS: This study represents the most comprehensive age- and gender
      controlled assessment of anorectal function using solid state technology. Gender
      influences some parameters of anorectal function. Our results could serve as a
      valuable resource of normative data.

PMID- 10086666
TI  - Prevalence and predictors of severe acute pancreatitis in patients with acquired
      immune deficiency syndrome (AIDS).
AB  - OBJECTIVE: Recent case control data suggested that a severe course of acute
      pancreatitis in HIV+ patients was 1) common (50% of cases), 2) poorly predicted
      by Ranson's criteria (sensitivity 41%), and 3) accurately predicted by a
      diagnosis of AIDS (positive predictive value 67%). However, the definition of
      severity included length of stay in hospital and excluded commonly accepted
      markers (local complications, systemic complications, and need for surgery). The
      aim of this study was to determine 1) the prevalence of severity and 2) the value
      of these predictors with regard to severity, as defined by commonly accepted
      standardized criteria in patients with AIDS and acute pancreatitis. METHODS: A
      retrospective review identified 50 patients with AIDS exhibiting clinical,
      laboratory, and/or radiological features of acute pancreatitis. RESULTS: Only
      five patients followed a severe course as defined by accepted markers. Of these
      patients, 29 had values available for at least nine of 11 of Ranson's criteria
      (sensitivity 80%, specificity 54%). Points were awarded most commonly for
      decreased serum Ca2+ (n = 14) and elevated serum LDH (n = 7). CONCLUSIONS: In
      patients with AIDS and acute pancreatitis at our institutions, 1) the prevalence
      of severity and 2) the sensitivity of Ranson's criteria with regard to severity
      is comparable to that reported in large historical case series of immunocompetent
      patients. Pseudohypocalcemia and/or elevation in LDH are frequent, likely due to
      the catabolic infectious disease state.

PMID- 10086667
TI  - Racial factors and the risk of chronic pancreatitis.
AB  - OBJECTIVE: It is unclear why some alcohol abusers develop alcoholic cirrhosis
      whereas others contract chronic pancreatitis. The aim of this study was to
      examine the importance of race as a risk factor for the development of chronic
      pancreatitis. METHODS: We compared the racial status of 1883 patients discharged
      with a first-listed diagnosis of two diseases strongly related to alcohol abuse:
      433 patients with chronic pancreatitis (ICD 5771) and 1450 patients with
      alcoholic cirrhosis (ICD 5712). Information came from discharge statistics
      maintained by two acute care hospitals in New York City and one acute care
      hospital in Lisbon, Portugal. The study period included the years 1989-1996 in
      the US and 1989-1994 in Portugal. RESULTS: A total of 215 (50%) of the 433
      chronic pancreatitis patients were black compared with 333 (23%) of the 1450
      patients with alcoholic cirrhosis. When adjusted for sex and hospital site,
      patients with pancreatitis were significantly more likely to be black than
      patients with cirrhosis (odds ratio 2.5, 95% confidence interval 1.9-3.2, p <
      0.001). CONCLUSIONS: In comparison with white patients, black patients are two to
      three times more likely to be hospitalized for chronic pancreatitis than
      alcoholic cirrhosis. This highly significant (p < 0.001) difference was observed
      in both men and women: in three different hospitals, and in two different
      countries. The explanation is unknown, but could be related to racial differences
      in diet, type or quantity of alcohol consumption, smoking, or ability to detoxify
      substances harmful to the liver or pancreas.

PMID- 10086668
TI  - Does endoscopic sphincterotomy cause prolonged pancreatobiliary reflux?
AB  - OBJECTIVE: Endoscopic sphincterotomy (ES) reduces sphincter function, which may
      allow reflux of pancreatic juice and intestinal contents into the common bile
      duct. The reflux, if present, may cause development of biliary tract carcinomas,
      as may anomalous pancreaticobiliary junction. We prospectively investigated
      pancreatobiliary and duodenobiliary reflux after ES. METHODS: In 15 patients with
      choledocholithiasis, ductal bile was sampled for amylase concentration and
      bacterial culture during endoscopic retrograde cholangiopancreatography, before
      and at 7 days to 5 yr after ES. To provide comparative data, ductal bile was
      sampled in 11 patients with gallbladder cholesterol polyps or anomalous
      pancreaticobiliary junction who did not undergo ES. RESULTS: Amylase
      concentration of ductal bile in patients with choledocholithiasis before ES was
      not different from that in patients with gallbladder polyps. Its concentration
      was increased 7 days after ES compared with that before ES, reaching the level of
      that in patients with anomalous pancreaticobiliary junction. Thereafter, amylase
      concentration gradually decreased, returning to that before ES by 1 yr. After ES,
      bactobilia occurred in 60-80% of patients, although none developed acute
      cholangitis. CONCLUSIONS: Although ES causes transient pancreatobiliary reflux,
      the reflux is abolished by 1 yr after ES. ES is unlikely to increase the risk for
      development of biliary tract carcinoma as long as cholangitis or bile duct stones
      do not recur.

PMID- 10086669
TI  - Effect of cisapride on secondary peristalsis in patients with gastroesophageal
      reflux disease.
AB  - OBJECTIVE: Improvement of esophageal acid clearance appears to be an important
      effect of cisapride in the treatment of reflux disease. The mechanism underlying
      this effect is not clear. Esophageal peristalsis is a major component of the acid
      clearance process. In normal subjects secondary peristalsis is an important
      mechanism of esophageal acid clearance during sleep, and this response appears to
      be impaired in patients with reflux esophagitis. The effects of cisapride on
      secondary peristalsis are not known. The aim of this study was to investigate the
      effects of cisapride on the triggering and characteristics of secondary
      peristalsis in patients with reflux esophagitis. METHODS: In 17 patients with
      reflux esophagitis and impaired secondary peristalsis cisapride, 10 mg q.i.d., or
      placebo were administered in a randomized double blind, crossover design for 4
      days separated by a 4-7 day washout period. On the fourth day of treatment,
      primary peristalsis and secondary peristalsis in response to 10- and 20-ml air
      boluses were assessed. RESULTS: Secondary peristaltic success and amplitude were
      greater with the 20-ml bolus than with the 10-ml bolus. However, cisapride had no
      effect on either secondary peristaltic success or amplitude. Cisapride also had
      no effect on primary peristalsis or basal LES pressure. CONCLUSIONS: The
      improvement in esophageal acid clearance by cisapride is not explainable by
      improvement in secondary peristalsis.

PMID- 10086670
TI  - The prevalence of gastroesophageal reflux disease in institutionalized
      intellectually disabled individuals.
AB  - OBJECTIVE: The prevalence of gastroesophageal reflux disease (GERD) was randomly
      investigated among Dutch and Belgian intellectually disabled individuals.
      METHODS: In six institutes including 1607 residents, 435 persons with IQ <50
      underwent 24-h esophageal pH-metry and were scored for possible predisposing
      factors and characteristic reflux symptoms. In 49 (11.2%) cases the test failed
      because of technical reasons. A pathological pH test was defined as a pH <4 for
      >4.5% of the measured time. Subjects with a pathological pH test (patients) were
      compared with those with a normal pH test (controls). RESULTS: Of the remaining
      individuals, 51.8% (200/386) showed a normal pH test, whereas 186 showed a
      pathological pH test (median duration pH <4: 14.2%, range: 4.5-78.4%). As
      possible predisposing factors scoliosis, cerebral palsy, use of anticonvulsant
      drugs or other benzodiazepines, and IQ <35 were found, whereas symptoms such as
      vomiting, hematemesis, rumination, and depressive symptoms were indicative for
      reflux. At endoscopy reflux esophagitis was diagnosed in 129 of the 186 patients
      (69.4%). In 61 (47.3%) of 129 patients, grade I, 43 (33.3%) grade II, 25 (19.4%)
      grade III/IV (Savary-Miller) were found. Barrett's esophagus was found in 18
      (14.0%) and peptic strictures in five (3.9%) cases. CONCLUSIONS: An abnormal 24-h
      pH-metry and symptoms suggestive for GERD were documented frequently in a large
      cohort of institutionalized intellectually disabled individuals. Further
      endoscopical evaluation confirmed the diagnosis of reflux esophagitis in the
      majority of these individuals.

PMID- 10086671
TI  - Enhancing compliance not a prerequisite for effective eradication of Helicobacter
      pylori: the HelP Study.
AB  - OBJECTIVE: The aim of this study was to compare cure rates of Helicobacter pylori
      (H. pylori) infection, compliance, and side effects in patients given 10 days of
      omeprazole 20 mg b.d., amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s.
      (OAM) or 10 days OAM plus compliance enhancing measures. METHODS: A total of 119
      H. pylori-positive patients were prospectively randomized to receive either 10
      days OAM or 10 days OAM plus compliance enhancing measures (medication in a dose
      dispensing unit, medication chart, an information sheet about H. pylori
      treatment, and phone call 2 days after starting therapy). H. pylori eradication
      was assessed by 13C-UBT at least 4 wk after cessation of therapy, compliance by
      phone interview on the last day of therapy and returned pill count, and side
      effects by phone interview and returned side effects form. RESULTS: In 113
      patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients (89.5%)
      after 10 days OAM and in 48 of 56 (85.7%) after 10 days OAM plus compliance
      enhancing measures (p = 0.54). In both groups 97% of medications were taken. Side
      effects were common (82% of patients). Both side effects (p = 0.001) and ulcer
      versus nonulcer at endoscopy (p = 0.016) were independent predictors of treatment
      failure; side effects also predicted noncompliance (p = 0.02). CONCLUSIONS: Ten
      days of OAM was effective for H. pylori eradication in our clinical population.
      Patient compliance was excellent and attempts to increase compliance had no
      impact on outcome or compliance. Side effects were very common and were
      significantly associated with treatment failure and decreased compliance.

PMID- 10086672
TI  - Characterization of autonomic dysfunction in patients with irritable bowel
      syndrome by means of heart rate variability studies.
AB  - OBJECTIVE: Our aim was to characterize autonomic dysfunction in patients with
      irritable bowel syndrome (IBS) using heart rate variability (HRV) studies.
      METHODS: EKG signals were obtained from 35 patients (mean age, 39.1 +/- 9.5 yr,
      M:F ratio = 2.9:1) and 18 healthy controls (mean age, 38.2 +/- 6.5 yr, M:F ratio
      = 2:1) in supine, standing, and deep-breathing modes. Fast Fourier transformation
      and autoregressive techniques were used to analyze the HRV power spectra in very
      low (VLF, 0.0078-0.04 Hz), low (LF, 0.04-0.14 Hz), and high (HF, 0.14-0.4 Hz)
      frequency bands. RESULTS: In the supine position, the VLF power spectral density
      (PSD) in IBS was significantly higher than normal (3 vs 1.3 beats per minute
      [bpm]2/Hz, p < 0.01). On changing from the supine to standing position, the
      normals (NC) had raised median PSDs in the VLF (1.3 vs 12.8 bpm2/Hz, p < 0.01)
      and LF (1.6 vs 6.1 bpm2/Hz, p < 0.01) bands, as a sign of increased sympathetic
      tone, whereas the median HF PSDs (parasympathetic tone) remained unchanged (1.8
      bpm2/Hz each, p = 0.8). Similarly, the IBS patients had increased VLF (3.04 vs
      14.93 bpm2/Hz, p < 0.01) and LF (2.8 vs 8.7 bpm2/Hz, p < 0.01) PSDs on standing
      up, but the HF PSD was also raised (from 2.4 to 5.7 bpm2/Hz, p = 0.04). On
      changing from standing to the deep-breathing mode, the normals had a significant
      increase in the HF (from 1.8 to 10.3 bpm2/Hz, p < 0.001) and a significant
      reduction of the VLF (from 12.8 to 2.2 bpm2/Hz, p < 0.01) PSDs. The reduction of
      the LF PSD was not significant (from 6.1 to 5.6 bpm2/Hz, p = 0.6). In IBS, HF PSD
      remained constant (5.7 bpm2/Hz each, p = 0.6), whereas the LF PSD increased from
      8.7 to 24.2 bpm2/Hz (p < 0.0001). The VLF PSD was reduced (from 14.9 to 4.1
      bpm2/Hz, p < 0.0001). In IBS, the median sympathovagal outflow ratio was
      significantly lower in the standing position (1.4 vs 2.8, p < 0.02) and higher in
      the deep-breathing mode (7.33 vs 0.42, p < 0.0001) than normal. CONCLUSIONS: IBS
      patients have reduced sympathetic influence on the heart period in response to
      orthostatic stress and diminished parasympathetic modulation during deep
      breathing.

PMID- 10086673
TI  - Gender, age, and body weight are the major predictive factors for bone mineral
      density in Crohn's disease: a case-control cross-sectional study of 113 patients.
AB  - OBJECTIVE: We conducted this study to assess bone mineral density and to evaluate
      conceivable predictive factors for bone loss in patients with Crohn's disease.
      METHODS: One hundred-thirteen patients with Crohn's disease and 113 healthy
      subjects, individually matched for gender, age, and body weight were
      investigated. The group consisted of 68 women and 45 men. The median duration of
      Crohn's disease was 6 yr. Two-thirds of the patients had been subjected to
      intestinal resection. Seventy-seven percent had at some time been treated with
      corticosteroids. Bone mineral density in the lumbar spine, the hip, and the total
      body skeleton was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS:
      In patients with Crohn's disease bone mineral density was not different from that
      of healthy controls except for a regional decrease in bone mineral density of the
      hip in female patients. The strongest predictors of bone mineral density were
      gender, age, and body weight. Corticosteroid use was only a weak predictor of
      diminished bone density. Duration of disease and intestinal resection had no
      predictive value for bone mineral density. CONCLUSIONS: Gender, age, and body
      weight are the major determinants of bone mineral density in patients with
      Crohn's disease. As in healthy individuals, the combined effect of these factors
      account for up to 50% of the variability in bone mineral density.

PMID- 10086674
TI  - To B or not to B: is tylosis B truly benign? Two North American genealogies.
AB  - Tylosis is a rare, autosomal dominant syndrome presenting with hyperkeratosis of
      the palms and soles of the feet. Two types have been identified. Late onset
      tylosis (type A) is reported to be associated with a high incidence of esophageal
      carcinoma, whereas early onset tylosis (type B) appears to be a benign disorder.
      This distinction has significant implications for surveillance and prognosis. We
      report two families exhibiting early onset type B tylosis, spanning five and
      seven generations, respectively, and believe these to be the first two extensive
      genealogies of tylosis type B reported in North America. They serve to verify the
      features of type B tylosis and its benign prognosis. The world literature is
      reviewed and clinical relevance is discussed. Recommendations for follow-up of
      afflicted individuals are proposed.

PMID- 10086675
TI  - Dysplastic gastroesophageal junction nodules--a precursor to junctional
      adenocarcinoma.
AB  - Adenocarcinoma of the gastroesophageal junction is a disease rapidly increasing
      in prevalence. The origin of these tumors is unclear. Barrett's esophagus,
      gastric cardia lesions, and mucus glands of the distal esophagus have been
      implicated. This case report presents two cases of patients who had chest pain
      leading to esophagogastroduodenoscopy. Both had small, benign-appearing nodules
      at the gastroesophageal junction in the absence of Barrett' s esophagus or
      gastric lesions. Biopsies revealed intestinal metaplasia with dysplasia in one
      patient and dysplasia of the mucus glands of the esophagus in the other. The
      first patient was followed for 8 months with serial biopsies, during which time
      the lesion became progressively more dysplastic, culminating in invasive cancer.
      These cases are presented to show that 1) benign-appearing gastroesophageal
      junction nodules may have malignant behavior, and 2) junctional cancer and high
      grade dysplasia can occur in the absence of Barrett's esophagus or gastric cardia
      lesions. Gastroesophageal junctional dysplasia/carcinoma may occur in small foci
      of intestinal metaplasia or in the mucus glands of the distal esophagus.

PMID- 10086676
TI  - Depression in adult untreated celiac subjects: diagnosis by the pediatrician.
AB  - Untreated celiac disease can lead to serious behavioral disorders. We describe
      three adult patients with undiagnosed or untreated celiac disease without
      particular intestinal signs, causing persistent depressive symptoms in three of
      the parents of our pediatric patients. In two of the three cases, the
      pediatrician suspected the diagnosis when taking the family history of the
      children. In fact, a diagnosis of celiac disease was made during childhood, when
      they had intestinal symptoms, but the gluten-free diet was spontaneously
      interrupted during the teenage period because of the disappearance of the typical
      intestinal signs. In the third case the mother was tested for antiendomysium
      antibodies (EmA), as she had a diagnosed celiac child. In all three patients, the
      depressive symptoms improved quickly with a gluten-free diet. In conclusion,
      celiac disease should be taken into consideration in the presence of behavioral
      and depressive disorders, particularly if they are not responsive to the usual
      antidepressive therapy.

PMID- 10086677
TI  - Recurrent subcutaneous abscess of the sternal region in ulcerative colitis.
AB  - An 18-yr-old female patient with extensive ulcerative colitis suffered from
      several episodes of recurrent aseptic subcutaneous abscesses of the sternal
      region with a course paralleling that of her colitis. The abscess seemed to occur
      secondarily to osteomyelitis of the sternum, which is a manifestation of the
      synovitis, acne, pustulosis, hyperostosis, and osteomyelitis (SAPHO) syndrome.

PMID- 10086678
TI  - Tension pneumothorax complicating diagnostic upper endoscopy: a case report.
AB  - Hypoxemia is common during various endoscopic procedures and may result from a
      variety of causes. These causes range from benign and otherwise easily reversible
      events like oversedation to potentially life threatening complications such as
      pneumothorax. Although pneumothorax has been reported secondary to
      gastrointestinal perforation as a complication of various therapeutic endoscopic
      procedures, there has been no report of pneumothorax without perforation. We
      report a case of a patient who developed severe hypoxemia and hemodynamic
      instability during diagnostic upper endoscopy as a result of pneumomediastinum
      and tension pneumothorax in the absence of any signs of gastrointestinal
      perforation and comment on various possible mechanisms. Immediate endotracheal
      intubation and bilateral chest tube placement resulted in prompt return of the
      patient's oxygenation and vital signs back to normal. This report enlarges the
      list of possible causes of hypoxemia during endoscopy and shows the importance of
      early and prompt recognition, which allowed directed therapy with a good outcome.

PMID- 10086679
TI  - Crohn's disease presenting as septic thrombophlebitis of the portal vein
      (pylephlebitis): case report and review of the literature.
AB  - Septic thrombophlebitis of the portal vein, or pylephlebitis, is an extremely
      rare complication of intraabdominal infection, most commonly caused by
      diverticulitis (1). The following case report describes a patient without
      previous significant medical history presenting with painless jaundice and
      presumed malignancy. Workup revealed pylephlebitis due to an ileal abscess
      secondary to Crohn's disease. The patient was successfully treated with broad
      spectrum antibiotics and terminal small bowel and right colon resection. To our
      knowledge, this is the first reported case of Crohn's disease diagnosed after
      presentation with pylephlebitis.

PMID- 10086680
TI  - Stress ulcer prophylaxis therapy: impact on gastric colonization.

PMID- 10086681
TI  - Functional MRI for the assessment of gastric motility--a better test?

PMID- 10086682
TI  - Helicobacter pylori and gastric cancer: proving the link.

PMID- 10086683
TI  - Nonorthodox therapeutic practices in inflammatory bowel disease.

PMID- 10086684
TI  - Omeprazole in asthma.

PMID- 10086685
TI  - A fatal case of paracentesis.

PMID- 10086686
TI  - Combination therapy with hepatitis B vaccine and interferon alfa in chronic
      hepatitis B.

PMID- 10086687
TI  - Intravenous vitamin complexes used in sporting activities and transmission of HCV
      in Brazil.

PMID- 10086688
TI  - Colorectal cancer presenting as Fournier's gangrene.

PMID- 10086689
TI  - Gastric metastases of breast carcinoma.

PMID- 10086690
TI  - Myoglobinuria in acute viral hepatitis.

PMID- 10086691
TI  - Obstructive jaundice as a recurrent symptom of small cell lung cancer.

PMID- 10086692
TI  - Correlation of histology, CLO, dental plaque, and saliva in patients undergoing
      upper GI endoscopy.

PMID- 10086693
TI  - Hepatitis C: does a healing state exist?

PMID- 10086694
TI  - New equipment in nuclear medicine, part 2: dual-head FDG coincidence detection
      cameras.

PMID- 10086695
TI  - U.S. Senator champions PET.

PMID- 10086696
TI  - Detecting myocardial salvage after primary PTCA: early myocardial contrast
      echocardiography versus delayed sestamibi perfusion imaging.
AB  - The extent of myocardial salvage after primary percutaneous transluminal coronary
      angioplasty (PTCA) in acute myocardial infarction (AMI) is variable and cannot be
      predicted on the basis of either vessel patency or early regional wall motion
      assessment. The aim of this study was to evaluate the reliability of
      microvascular integrity, as shown by myocardial contrast echocardiography (MCE),
      as an indicator of tissue salvage and a predictor of late functional recovery,
      and to compare MCE with the quantification of tracer activity in sestamibi
      perfusion imaging. METHODS: Twenty-six patients with AMI who received successful
      treatment with primary PTCA were examined with MCE during cardiac catheterization
      immediately before and after vessel recanalization. Myocardial contrast effect
      was scored as 0 (absent), 0.5 (partial) or 1 (normal). Wall motion was assessed
      by two-dimensional echocardiography on admission and 1 mo later with a 16-segment
      model and 4-point score. Resting sestamibi SPECT was collected within 1 wk after
      AMI. The risk area was defined by MCE as the sum of the segments with no
      perfusion (score 0) before PTCA. Myocardial viability was defined by MCE as an
      increase in contrast score in the same segments after PTCA and by sestamibi SPECT
      as a preserved tracer activity (>60% of peak activity). The functional recovery
      after 1 mo detected by two-dimensional echocardiography was the reference
      standard for viability. RESULTS: A total of 50 segments showed perfusion defects
      before PTCA (risk area). Immediately after PTCA, the MCE score increased in 44 of
      50 segments, whereas sestamibi SPECT showed preserved activity in 22 of 50
      segments. After 1 mo, the wall motion score decreased in 22 of 50 segments
      (viable segments) and was unchanged in the remaining 28 segments. Thus, MCE
      showed a sensitivity of 91% and a specificity of 14% in detecting viable
      myocardium, whereas sestamibi SPECT showed a lower sensitivity (68%) but a
      significantly higher specificity (75%; P < 0.00001). The positive predictive
      values were 45% and 68% for MCE and SPECT (P < 0.005), respectively, and the
      negative predictive values were 67% and 71%, respectively. On a patient basis,
      SPECT was more specific (79% versus 21%; P < 0.01) and showed a higher overall
      predictive accuracy (88% versus 50%; P < 0.01) than MCE. CONCLUSION: The
      demonstration of microvascular integrity by MCE performed immediately after
      primary PTCA has a limited diagnostic value in predicting salvaged myocardium.
      Conversely, tracer activity quantification in resting sestamibi SPECT performed
      in a later stage is confirmed to be a reliable approach for recognizing
      myocardial stunning and predicting functional recovery.

PMID- 10086697
TI  - Loss of 123I-MIBG uptake by the heart in Parkinson's disease: assessment of
      cardiac sympathetic denervation and diagnostic value.
AB  - Myocardial imaging with 123I-metaiodobenzylguanidine (MIBG) was performed on 35
      patients with Parkinson's disease and 24 control subjects to evaluate cardiac
      sympathetic function in patients with Parkinson's disease, verify this phenomenon
      and examine whether myocardial MIBG uptake and clearance are correlated with the
      clinical severity of Parkinson's disease. METHODS: We studied 35 patients with
      Parkinson's disease and 24 control subjects with other central nervous system
      diseases. The latter group consisted of 12 subjects with other neurodegenerative
      disorders (4 with spinocerebellar degeneration, 2 with amyotrophic lateral
      sclerosis, 3 with progressive supranuclear palsy and 3 with corticobasal
      degeneration and 12 patients with cerebral infarction (CI), 6 with vascular
      parkinsonism and 6 without it. Early and delayed images of the anterior view were
      obtained 15 min and 4 h after injection of 123I-MIBG, respectively. MIBG uptake
      was quantified by calculating a heart-to-mediastinum count (H/M) ratio. RESULTS:
      The H/M ratio was markedly reduced in the patients with Parkinson's disease (II
      to V on the Hoehn and Yahr scale) compared with the control subjects. None of the
      subjects with neurodegenerative diseases showed a marked decrease in myocardial
      MIBG uptake nor did any subject with CI. CONCLUSION: Our findings indicate that,
      in Parkinson's disease, a reduction in myocardial MIBG uptake is a very common,
      specific phenomenon that can be used to detect cardiac autonomic dysfunction to
      diagnose Parkinson's disease, particularly in patients without typical signs and
      symptoms.

PMID- 10086698
TI  - Double-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing
      breast cancer.
AB  - The goal of our study was to assess the value of both scintimammography with
      99mTc-sestamibi (SMM) and trans-scan (T-scan) in detecting breast cancer.
      METHODS: A total of 121 women were evaluated by palpation, mammography, SMM and T
      scan. SMM was performed in the prone, breast dependent position. Immediate and
      delayed views (double-phase) were obtained. T-scan is a new breast imaging method
      that maps noninvasively the distribution of tissue electrical impedance and
      capacitance. RESULTS: SMM had 88.9% sensitivity, 88.4% specificity and 88.4%
      accuracy in detecting breast cancer. SMM had 100% sensitivity in detecting breast
      tumors >1 cm and only 66% sensitivity in detecting tumors <1 cm. T-scan had 72.2%
      sensitivity and 67% specificity in detecting breast cancer. It detected one more
      breast cancer than SMM, at the expense of 27 additional false-positive results.
      CONCLUSION: Double-phase SMM was sensitive and specific in detecting breast
      cancer. This method may reduce the rate of negative breast biopsies in tumors >1
      cm. T-scan was only moderately accurate in detecting breast cancer. Its addition
      to SMM did not improve significantly the rate of breast cancer detection.
      However, because of its complete noninvasiveness, large-scale applicability and
      low cost, T-scan deserves further refining.

PMID- 10086699
TI  - FDG and L-[1-11C]-tyrosine imaging of soft-tissue tumors before and after
      therapy.
AB  - This study was undertaken to investigate the relationship of PET using
      fluorodeoxyglucose (FDG) or L-[1-11C]-tyrosine (TYR) with histopathologic
      findings in soft-tissue tumors, before and after therapy. Histopathologic
      parameters that were studied were tumor grade, mitotic rate, proliferation
      activity and amount of necrosis. METHODS: PET with either FDG or TYR was
      performed in 55 patients with a lesion suspected to be a malignant soft-tissue
      tumor. In 28 patients, a second PET study was performed after therapy. Metabolic
      rate of glucose consumption (MRglc) and protein synthesis rate (PSR) were
      calculated. Histologic parameters were obtained from a biopsy specimen that was
      taken just after the first PET study and from the tumor remnant that was resected
      after therapy. RESULTS: MRglc correlated with tumor grade (r = 0.71) and mitotic
      rate (r = 0.68) but not with proliferation or necrosis. After therapy, there was
      no longer a correlation with mitotic rate. PSR correlated with tumor grade (r =
      0.53), mitotic rate (r = 0.73) and proliferation (r = 0.66). After therapy,
      correlation with mitosis and proliferation had improved, and a negative
      correlation was found between PSR and necrosis (r = -0.74). CONCLUSION: These
      results validate the use of both FDG and TYR to give an in vivo indication of
      histologic tumor parameters. However, FDG gives a better indication of tumor
      grade, whereas TYR is more accurate in predicting mitotic rate and proliferation,
      especially after therapy. FDG may therefore not be the most suited tracer for
      monitoring therapy. TYR might be more appropriate for that purpose.

PMID- 10086700
TI  - Staging and monitoring of malignant lymphoma of the bone: comparison of 67Ga
      scintigraphy and MRI.
AB  - The aim of this study was two-fold: to compare 67Ga scintigraphy with MRI (a) for
      the staging of malignant lymphoma of the bone and (b) with regard to accuracy in
      detecting residual disease after first-line chemotherapy for restaging. METHODS:
      Twenty-one patients with 36 malignant osseous lesions were examined, including 7
      patients with primary or multifocal osseous lymphoma and 14 patients with
      malignant lymphoma and simultaneous or secondary involvement of the bone. After
      first-line therapy, MRI and 67Ga scintigraphy were performed on 13 patients. The
      remission status based on all clinical and radiological findings during the
      follow-up was used as the gold standard. RESULTS: The osseous lesions were
      located on the axial skeleton in 64% of patients and on the appendicular skeleton
      in 36%. 67Ga scintigraphy detected 77% of the osseous lesions examined by MRI.
      For restaging after first-line therapy, MRI had a sensitivity of 90% and a
      specificity of 80% when dynamic MRI information was included. There were several
      false-positive results as a result of the pathologic increase in signal intensity
      ratios of reactive hematopoietic regions after chemotherapy. For 67Ga
      scintigraphy, a sensitivity of 70% and a specificity of 93% were calculated.
      CONCLUSION: These data show that monitoring malignant lymphoma of the bone still
      presents diagnostic problems. Given the high sensitivity of MRI and the high
      specificity of 67Ga scintigraphy but the limited specificity of MRI and
      sensitivity of 67Ga scintigraphy, both methods are valuable but should be used as
      complementary diagnostic tools.

PMID- 10086701
TI  - Lobar decrease in 99mTc-GSA accumulation in hilar cholangiocarcinoma.
AB  - Hilar cholangiocarcinoma can obstruct hepatic ducts and involve the portal veins.
      Both biliary stasis and decrease in portal venous flow are known to reduce 99mTc
      diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA)
      accumulation. The specific relationship between these pathological conditions due
      to hilar cholangiocarcinomas and 99mTc-GSA accumulation has never been clarified.
      METHODS: Sixteen patients with hilar cholangiocarcinomas who underwent 99mTc-GSA
      liver scintigraphy were reviewed. The relationship between significant decrease
      in 99mTc-GSA accumulation and lobar biliary stasis, or decrease in the portal
      venous flow, was evaluated. Average counts of region of interest placed in both
      right and left lobes were compared in the same transaxial SPECT section. Count
      ratios of right and left lobes were calculated. RESULTS: Significant lobar
      decrease in 99mTc-GSA accumulation was observed in 6 of the 16 patients.
      Ipsilateral portal venous stenosis or obstruction was seen in all these 6
      patients, whereas ipsilateral portal venous stenosis or obstruction was seen in
      only 1 of the other 10 patients. Symmetric bile duct dilatation was seen in 13
      patients, and asymmetric bile duct dilatation was seen in 3. Lobar decrease in
      99mTc-GSA accumulation correlated well with decrease in ipsilateral portal venous
      flow (P < 0.0005). The count ratio was significantly reduced when unilateral
      portal venous flow decreased (P < 0.05). CONCLUSION: Using 99mTc-GSA liver
      scintigraphy, we can predict lobar decrease in ipsilateral portal venous flow and
      monitor hepatic functional lateralities in patients with hilar
      cholangiocarcinomas.

PMID- 10086702
TI  - 18F alpha-methyl tyrosine PET studies in patients with brain tumors.
AB  - We have developed 18F-labeled alpha-methyl tyrosine (FMT) for PET imaging. The
      aim of this study was to evaluate the clinical application potential of FMT for
      patients with brain tumors. METHODS: Eleven healthy volunteers and 20 patients
      with brain tumors were injected with 185 MBq (5 mCi) FMT. In 3 healthy
      volunteers, whole-body imaging and urinary and plasma analysis were conducted for
      the assessment of the biodistribution of FMT. The normal range of cortical
      standardized uptake value (SUV) as a reference for comparing tumor SUV of FMT was
      estimated by using PET data obtained at 30 min postinjection in 8 healthy
      volunteers. Dynamic PET scans were conducted for 100 min in 4 healthy volunteers
      and for 30 min in 15 patients with brain tumors. The 10-min static images in
      another 4 volunteers and all patients were obtained at 30 min postinjection. In
      13 patients, FMT uptake in the brain tumor was compared with 18F
      fluorodeoxyglucose (FDG). Tumor-to-normal cortex count (T/N) ratio and tumor-to
      white matter count (T/W) ratio and SUVs of brain tumors were determined on FMT
      and FDG PET images. RESULTS: Approximately 1480 MBq (40 mCi) FMT were produced in
      one radiosynthesis. Percentage injected dose (%ID) of FMT in the brain ranged
      from 2.8% to 4.9%, and approximately 50%ID of FMT was excreted in urine during 60
      min postinjection, of which 86.6% was unmetabolized FMT. A faint physiological
      brain uptake with SUV of 1.61 +/- 0.32 (mean +/- SD, n = 8) was observed in
      healthy volunteers. Tumor SUV of FMT ranged from 1.2 to 8.2, with mean value of
      2.83 +/- 1.57 (n = 23), which was significantly higher than that of the cortical
      area in healthy volunteers (P < 0.01). T/N and T/W ratios of FMT were
      significantly higher than those of FDG (2.53 +/- 1.31 versus 1.32 +/- 1.46, P <
      0.001; 3.99 +/- 2.10 versus 1.39 +/- 0.65, P < 0.0001, respectively). CONCLUSION:
      FMT, like other radiolabeled amino acids, can provide high-contrast PET images of
      brain tumors.

PMID- 10086703
TI  - Hypotensive response to captopril: a potential pitfall of scintigraphic
      assessment for renal artery stenosis.
AB  - A characteristic pattern seen on captopril renography is described that is due to
      systemic hypotensive response. Most patients with these findings on captopril
      renography do not receive renal artery angiograms in our clinic because it is
      usually recognized. However, this pattern has received little attention in the
      medical literature and may be misinterpreted as being due to physiologically
      significant renal artery hypertension. METHODS: Over the last 3 y, renal artery
      angiograms were performed on three patients with systemic hypotensive response
      pattern on captopril renography. This allowed a unique opportunity to correlate
      the results of the captopril renogram with the renal artery angiograms in this
      patient population. Captopril renography was performed with a glomerular
      filtration agent, diethylenetriamine pentaacetic acid (DTPA), and a tubular
      agent, o-iodohipurate (OIH). RESULTS: Renal artery angiograms showed no evidence
      of renal artery stenosis in three patients with systemic hypotensive response
      pattern on captopril renography. Systemic hypotension on captopril renograms
      results in preserved uptake of both DTPA and OIH and hyperconcentration in the
      cortex and collecting system. CONCLUSION: The systemic hypotensive response
      pattern seen on captopril renography is a distinctive pattern that does not
      represent physiologically significant renal artery stenosis.

PMID- 10086704
TI  - Value of captopril renal scintigraphy in hypertensive patients with renal
      failure.
AB  - The aims of this study were to show the value of captopril renal scintigraphy for
      detecting a renovascular cause in hypertensive patients with renal failure and to
      assess the ability to predict the beneficial effect of revascularization on renal
      function. METHODS: Thirty-eight patients with renal failure (mean glomerular
      filtration rate = 35 mL/min) underwent renal scintigraphy after injection of
      99mTc-mercaptoacetyltriglycine. Baseline scintigraphy was performed, and the test
      was repeated 24 h later after oral administration of 50 mg captopril given 60 min
      before the test. RESULTS: In 5 of 6 patients with a renovascular cause for renal
      failure, and 2 of 3 patients with a probable arterial pathology, scintigraphy had
      a high probability. The result was indeterminate in the other 2 patients. In 5 of
      11 patients with negative arteriography and 14 of 18 patients with probable
      absence of renovascular pathology, we found a low probability of functional renal
      artery stenosis. Six revascularization procedures were performed and were
      predictive of a beneficial effect in 5 patients. Time of peak activity was an
      effective predictor in each case. CONCLUSION: In hypertensive patients with renal
      failure, captopril renal scintigraphy can detect hemodynamic dysfunction
      downstream from a renal artery stenosis and can predict the beneficial effect of
      revascularization in some cases.

PMID- 10086705
TI  - Increased renal retention of 99mTc-methylene diphosphonate after nephron-sparing
      surgery.
AB  - Nephron-sparing surgery has become established as an effective treatment for
      localized renal cell carcinoma when preservation of renal function is necessary.
      The surgery usually requires temporary renal artery occlusion and may induce
      ischemic renal damage. In this study, we retrospectively evaluated renal activity
      on bone scintigraphy after nephron-sparing surgery. METHODS: Eleven patients who
      underwent nephron-sparing surgery for renal cell carcinoma and had a normal
      contralateral kidney were studied. A total of 12 bone scintigraphy images with
      99mTc-labeled methylene diphosphonate were obtained within 1 y after surgery in
      these patients to assess skeletal metastasis. Activity in the spared renal
      parenchyma was compared visually with that in the contralateral normal kidney.
      RESULTS: The tumor was successfully resected in every patient, and no clinically
      significant complications occurred. Activity in the spared renal parenchyma was
      elevated in six of seven examinations performed within 21 d after surgery. In
      three examinations, the increase in renal activity was heterogeneous, being
      relatively prominent near the surgical margin. Increased renal activity was not
      observed on five examinations performed 3 mo or more after surgery. CONCLUSION:
      Renal retention of bone-seeking agents is elevated in the early period after
      nephron-sparing surgery, probably as a result of ischemic insult during the
      surgical procedure. Bone scintigraphy may aid in evaluating the presence and
      degree of ischemic damage of the spared renal parenchyma.

PMID- 10086706
TI  - Effect of obesity on red cell mass results.
AB  - Measurement of red cell mass with isotope dilution remains an important
      diagnostic test in the evaluation of patients with suspected polycythemia vera
      (PCV). Results and reference ranges are typically expressed in units normalized
      for body weight (mL/kg). Obesity is common in polycythemic patients, and it is
      important to know how the various published normative ranges compare across a
      wide range of body weights. METHODS: We retrospectively reviewed 51 consecutive
      patients referred for red cell mass determination with 51Cr red blood cell
      dilution. Results were expressed in milliliters per kilogram (mL/kg) by using the
      actual patient weight and after adiposity adjustments using ideal body weight,
      body mass index (BMI) and combinations of height-weight, including body surface
      area. Results were classified as normal, elevated or PCV. RESULTS: There was a
      high prevalence of obesity in our population (28/51 [55%] with BMI > 27 kg/m2,
      BMI range 16.0-54.8 kg/m2). The method used to compensate for obesity had a
      dramatic effect on the derived red cell mass, the fraction of patients with
      elevated measurements and the fraction of patients meeting criteria for PCV.
      Concordance for categorization as normal, elevated or PCV by all methods was only
      47.1%. CONCLUSION: Obesity is a common confounding factor in the interpretation
      of red cell mass measurements. Currently published reference ranges generate
      inconsistent results when extrapolated to obese patients. Further normative data
      on obese subjects are needed to determine which method (if any) is optimal.

PMID- 10086707
TI  - Prospective validation of single plasma sample 99mTc-ethylenedicysteine clearance
      in adults.
AB  - 99mTc-L,L-ethylene, L, dicysteine (EC) clearance shows strong correlation with
      orthoiodohippurate clearance, and it is possible to estimate effective renal
      plasma flow from 99mTc-EC clearance. In routine clinical studies, it is practical
      to use the one or two plasma sample method instead of multiple plasma samples for
      clearance determination. A single-sample technique was developed for 99mTc-EC,
      and a regression formula was generated. A prospective study tested the validity
      of this regression formula. METHODS: The study population was composed of 26
      patients with a wide range of renal function. Multiple plasma sample 99mTc-EC
      clearances were calculated from all patients using the open two-compartment
      model. Single plasma sample clearances were also determined from the 54-min
      plasma sample using the regression formula published previously. RESULTS: The
      multiple-sample plasma clearance of 99mTc-EC ranged from 46 to 668 mL/min with a
      mean of 300.76 +/- 150.73 mL/min. The clearances obtained from the 54-min plasma
      sample ranged from 49 to 699 mL/min, with a mean of 297.39 +/- 152.23 mL/min.
      There was an excellent correlation between the clearances obtained by the two
      techniques (r = 0.99, slope = 0.9911). The standard error of estimation was found
      to be 25.9 mL/min. CONCLUSION: This study suggests that 99mTc-EC clearance can be
      estimated from 54-min plasma samples with an acceptable error of estimation for
      most routine clinical studies.

PMID- 10086708
TI  - Coincidence imaging with a dual-head scintillation camera.

PMID- 10086709
TI  - Frequency encoding for simultaneous display of multimodality images.
AB  - An original method for simultaneous display of functional and anatomic images,
      based on frequency encoding (FE), merges color PET with T1-weighted MR brain
      images, and grayscale PET with multispectral color MR images. A comparison with
      two other methods reported in the literature for image fusion (averaging and
      intensity modulation techniques) was performed. METHODS: For FE, the Fourier
      transform of the merged image was obtained summing the low frequencies of the PET
      image and the high frequencies of the MR image. For image averaging, the merged
      image was obtained as a weighted average of the intensities of the two images to
      be merged. For intensity modulation, the red, green and blue components of the
      color image were multiplied on a pixel-by-pixel basis by the grayscale image. A
      comparison of the performances of the three techniques was made by three
      independent observers assessing the conspicuity of specific MRI and PET
      information in the merged images. For evaluation purposes, images from seven
      patients and a computer-simulated MRI/PET phantom were used. Data were compared
      with a chi-square test applied to ranks. RESULTS: For the depiction of MRI and
      PET information when merging color PET and T1-weighted MR images, FE was rated
      superior to intensity modulation and averaging techniques in a significant number
      of comparisons. For merging grayscale PET with multispectral color MR images, FE
      and intensity modulation were rated superior to image averaging in terms of both
      MRI and PET information. CONCLUSION: The data suggest that improved simultaneous
      evaluation of MRI and PET information can be achieved with a method based on FE.

PMID- 10086710
TI  - Automatic three-dimensional multimodality registration using radionuclide
      transmission CT attenuation maps: a phantom study.
AB  - Coregistration of images from a single subject, acquired by different modalities,
      is important in clinical diagnosis, surgery and therapy planning. The purpose of
      this study was to evaluate, using a physical torso phantom, a novel, fully
      automated method for three-dimensional image registration of CT and SPECT, using
      radionuclide transmission (RNT) attenuation maps. METHODS: We obtained CT scans
      and SPECT scans paired with RNT maps of an anthropomorphic cardiac phantom. RNT
      attenuation maps were acquired using an uncollimated 99mTc-filled flood source.
      RNT and SPECT scans were acquired in the same spatial orientation (usual clinical
      practice in nonuniform attenuation correction). In addition, CT attenuation maps
      (CTMAPs) for 99mTc SPECT were generated from CT by linear energy scaling. RNT
      maps were registered to CT and CTMAPs by iterative simplex minimization of count
      difference and uniformity index (sum of RNT map intensity variances corresponding
      to each intensity level in the CT volume). In each iteration, three shifts and
      three angles were adjusted. To register SPECT to CT, we applied the RNT
      transformation parameters to SPECT. RESULTS: RNT maps could be registered to CT
      and CTMAP images using both criteria. The average three-dimensional distance
      between landmark and automated registration was 2.5 +/- 1.2 mm for count
      difference and 3.3 +/- 1.3 mm for uniformity index. The three-dimensional
      reproducibility errors were 1.2 +/- 0.7 mm for count difference, 2.1 +/- 0.5 mm
      for uniformity index and 2.3 +/- 1.0 mm for manual marker registration. The
      minimization of uniformity index was robust when up to 50% CT or RNT slices were
      missing and was not affected significantly (<2 mm) by realistic variation in CT
      values (+/- 12 Hounsfield units). CONCLUSION: In addition to typical use in
      nonuniform attenuation correction, RNT maps can be used for fully automated three
      dimensional registration of SPECT to CT. Such registration is not affected by
      features and quality of SPECT images and avoids difficulties associated with
      fiducial markers. Our method can be applied to SPECT-CT registration of various
      organs, such as brain, heart, lungs, breasts and abdomen, including oncological
      scans.

PMID- 10086711
TI  - Attenuation compensation in 99mTc SPECT brain imaging: a comparison of the use of
      attenuation maps derived from transmission versus emission data in normal scans.
AB  - Brain SPECT imaging using 99mTc lipophilic tracers such as hexamethyl
      propyleneamine oxime (HMPAO) attempts to estimate cerebral, cerebellar and
      subcortical perfusion by assessing the relative amount of tracer uptake among
      these regions. Most commonly, comparison is made with cerebellar activity.
      Because the assessment of relative tracer uptake may be rendered inaccurate by
      photon attenuation by the nonuniform attenuation properties of the head, brain
      SPECT reconstructions have been compared using attenuation correction (AC) with
      various methods for estimating the attenuation map. METHODS: Patients underwent
      99mTc-HMPAO brain SPECT with transmission line source AC hardware. In addition to
      the emission dataset, emission downscatter and transmission datasets were
      acquired. Iterative reconstructions using three different attenuation maps were
      investigated. These included: (a) that obtained from transmission imaging, (b)
      that obtained from segmentation of a reconstruction from a lower energy Compton
      scatter window and (c) a slice-independent, uniform, elliptical attenuation map.
      No AC was also compared. RESULTS: Count profiles in patients having brain
      perfusion SPECT scans showed a significant difference in region count estimates
      in the brain depending on whether AC is used as well as on the attenuation map
      used. Scatter-based AC is able to provide external contour detection and
      attenuation compensation based on that contour, whereas transmission-based AC
      provides external contour detection as well as internal, nonuniform attenuation
      estimation and AC. If one considers transmission AC to be the clinical "gold
      standard," non-attenuation-corrected as well as fixed-ellipsoid, uniform
      attenuation-corrected studies provided unreliable regional estimates of tracer
      activity. CONCLUSION: This study shows the significant difference in clinical
      brain SPECT count profiles depending on how and whether there is compensation for
      attenuation. Based on prior studies validating the improved quantitative accuracy
      of SPECT using transmission-based AC, this study suggests that clinical 99mTc
      brain perfusion SPECT would benefit from and, in situations demanding rigorous
      quantitative assessment, requires transmission-based AC. Estimating attenuation
      maps with scatter-based methods was the next most accurate (clinical) method
      tested and can be used if and when transmission imaging cannot be used.

PMID- 10086712
TI  - Biodistribution, radiation dosimetry and pharmacokinetics of 111In-antimyosin in
      idiopathic inflammatory myopathies.
AB  - In view of the established role of 111In-antimyosin in the detection of heart
      muscle pathology, radiation dose estimates were made for this substance.
      Biodistribution and biokinetic data were obtained from our studies, which failed
      to show abnormal uptake of 111In-antimyosin in localized sites of skeletal muscle
      involvement in patients with idiopathic inflammatory myopathies. METHODS: After
      intravenous administration of 74 MBq (2 mCi) 111In-antimyosin, gamma camera
      scintigraphy was performed in 12 adult patients with inflammatory muscle disease
      and in 2 control patients. Six whole-body scans were performed over 72 h, and
      uptake of 111In-antimyosin in organs was quantified using an attenuation
      corrected conjugate counting method. Residence times in source organs were used
      with MIRDOSE software to obtain radiation dose estimates. Pharmacokinetic
      parameters were derived from serial whole-blood and plasma 111In concentrations.
      RESULTS: The tracer cleared slowly from the circulation, and highest organ
      uptakes were found in the marrow and liver; kidneys showed the highest
      concentrations. Uptake was also evident in spleen, the facial image and male
      genitalia. CONCLUSION: For a typical administered activity of 74 MBq 111In
      antimyosin, the kidneys receive the highest dose (58 mSv), and the effective dose
      is 11 mSv. Radioactivity was cleared from plasma at an average rate of 136 mL/h,
      and the mean steady-state distribution was approximately 5 L plasma.

PMID- 10086713
TI  - Myocardial metabolism of 123I-BMIPP in a canine model with ischemia: implications
      of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart
      disease.
AB  - 123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid
      analog for SPECT imaging. This radiopharmaceutical possesses the unique property,
      that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic
      heart disease. However, the reason of this mechanism remains unclear. METHODS:
      Using open-chest dogs under anesthesia, we made a system to release all the blood
      of the great cardiac vein outside without recirculation, if necessary. Left
      anterior descending artery (LAD) was occluded for 30 min after reperfusion. After
      the injection of BMIPP into LAD, blood samplings from the cardiac vein and
      abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs)
      were performed, and then compared with the normal control. The catabolites of
      BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high
      performance liquid chromatography (HPLC) in the efflux study. Thin-layer
      chromatography (TLC) technique was introduced in the tissue analytical study.
      RESULTS: Although the rapid extraction of BMIPP from the plasma into the
      myocardium and the subsequent retention were unchanged, the early washout (8 min)
      of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05)
      with ischemia. The metabolites from the myocardium consisted of backdiffusion of
      nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among
      these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly
      increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early
      phase with ischemia. In tissue, the radioactivity was concentrated in the
      triglyceride pool even in the early phase, and in addition, BMIPP and alpha
      oxidized metabolite significantly decreased in the early phase with ischemia (t =
      1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2
      min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). CONCLUSION: These results show
      that backdiffusion of nonmetabolized BMIPP from the myocardium increased and
      BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting
      backdiffusion of nonmetabolized BMIPP might play an important role in myocardial
      perfusion-metabolism mismatch on SPECT images in patients with ischemic heart
      disease.

PMID- 10086714
TI  - The relationship of glycosylation and isoelectric point with tumor accumulation
      of avidin.
AB  - Radiolabeled avidin markedly accumulated in intraperitoneal tumors and was
      cleared rapidly from circulation when given intraperitoneally. This study
      investigated the mechanisms of the tumor localization of avidin. METHODS: Avidin
      was deglycosylated through endoglycosydase-H digestion and/or neutralized by
      acetylation of its lysine amino acids with acetic acid N-hydroxysuccinimide
      ester. Avidin and modified avidins were analyzed using sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS/PAGE) and isoelectric focusing. A tumor
      model was established by intraperitoneal injection of human colon cancer cells,
      LS180, in nude mice. Avidin and modified avidins were labeled with 111In using
      diethyleneamine pentaacetic acid-biotin and were administered intraperitoneally
      into the tumor-bearing mice. The biodistribution of radioactivity was examined 2
      and 24 h postinjection. RESULTS: Deglycosylated avidins revealed a major band of
      smaller molecules on SDS/PAGE. The isoelectric point of neutralized avidins was
      reduced to less than 5, whereas that of unneutralized avidins was more than 9.5.
      Biodistribution study demonstrated that liver uptake was decreased by
      deglycosylation and kidney accumulation was decreased by neutralization,
      respectively. The blood clearance was remarkably slowed by combined modification
      of deglycosylation and neutralization. The tumor uptake of radioactivity was
      reduced by either deglycosylation or neutralization and was further decreased
      with combined modification. CONCLUSION: Both high glycosylation and positive
      charge of avidin contributed to its accumulation in tumor. This study may
      facilitate development of a new vehicle for the delivery of therapeutic agents to
      intraperitoneal tumors.

PMID- 10086715
TI  - Pretargeting of bacterial endocarditis in rats with streptavidin and 111In
      labeled biotin.
AB  - A radioimaging approach for the detection of endocarditis has been investigated
      using two-step pretargeting with streptavidin and radiolabeled biotin. METHODS:
      Hemodynamic alterations within the rat heart were induced by placing an in
      dwelling catheter into the left ventricle through the aortic valves. The animals
      were subsequently infected with Staphylococcus aureus through a tail vein. After
      an incubation period, rats were first injected with streptavidin and, 2 h later,
      with 111In-labeled ethylene-diaminetetraacetic acid-biotin. Whole-body gamma
      camera images were taken 4-5 h postinjection of the radiolabeled biotin. Control
      animals consisted of catheterized but uninfected, infected but uncatheterized and
      normal untreated rats. As a further control, the labeled biotin was administered
      to a study animal without the preadministration of streptavidin. RESULTS:
      Histology showed typical endocarditic changes in the hearts of study animals with
      massive deposition of gram-positive cocci. Catheterized but uninfected animals
      showed alterations corresponding to nonbacterial thrombotic endocarditis.
      Macroautoradiography showed accumulation of radiolabel in the endocarditic
      vegetations of study animals. Whole-body gamma camera images showed important
      cardiac uptake in 7 of 8 catheterized and infected animals and in 3 of 6
      catheterized but uninfected animals. Normal rats and those infected but not
      catheterized showed negative results by histology, autoradiography and imaging.
      The percent uptake of the injected dose in the heart was 0.20 (SD = 0.13) in
      catheterized and infected animals, 0.12 (SD = 0.10) in catheterized but
      uninfected animals, 0.10 (SD = 0.04) in infected but uncatheterized animals and
      0.04 (SD = 0.01) in normal control animals. CONCLUSION: The two-step pretargeting
      approach using streptavidin and 111In-labeled biotin was used successfully to
      detect S. aureus-induced bacterial endocarditis in rats.

PMID- 10086716
TI  - In vivo distribution and identification of 11C-activity after injection of
      [methyl-11C]thymidine in Wistar rats.
AB  - [Methyl-11C]thymidine and PET offer an in vivo, noninvasive quantitative approach
      for studying nucleoside uptake in cells on the condition the fraction of [methyl
      11C]thymidine (in deoxyribonucleic acid [DNA] or as DNA precursors) versus the
      total accumulated activity is known. METHODS: In a group of normal (n = 6) and a
      group of tumor-bearing (n = 3) Wistar rats, the biodistribution of 11C-activity
      was studied dynamically. In a second group of rats (n = 6), the animals were
      killed at 20 min postinjection and the organs and tissues of interest (liver,
      heart, brain, duodenum and tumor) were measured for activity and then
      homogenized. 11C-activity in each fraction (cell debris, protein/ DNA-fraction,
      lipids and supernatant) was measured. The supernatant was analyzed by high
      performance liquid chromatography (HPLC)-radiochromatography for identification
      of different 11C-labeled compounds. RESULTS: After venous injection, most of the
      11C-activity was rapidly trapped in the liver and in fast-dividing tissue (e.g.,
      duodenum); minor activity was located in the bladder, kidneys, heart and brain.
      HPLC separation showed that the 11C-activity of the liver tissue consisted of
      metabolites only. For the duodenum and tumor, at least 55% of the 11C-activity
      was precipitated in the protein/DNA-fraction and about 60% as DNA precursors
      (thymidine, 2'-deoxythymidine 5'-monophosphate and 2'-deoxythymidine 5'-
      triphosphate ) in the supernatant. CONCLUSION: Despite the in vivo metabolism,
      major 11C-activity in rapidly dividing tissue consists of [methyl-11C]thymidine
      incorporated in the DNA. Catabolism takes place mainly in the liver where the
      degradation products are stored. PET quantification data using [methyl-11C]
      thymidine can give information about thymidine incorporation in DNA and cell
      proliferation of tumors.

PMID- 10086717
TI  - Oncogenes, cancer and imaging.
AB  - At the dawn of the 21st century, nuclear oncology is undergoing a formidable and
      rapid mutagenesis. The progress in radiochemistry, radiopharmacy and, foremost,
      the advances in molecular oncology are the determinant mutagenic factors.
      Mutation, amplification, deletion or translocation of deoxyribonucleic acid
      segments in proto-oncogenes and tumor suppressor genes also called anti-oncogenes
      account for the uncontrolled cell growth and proliferation resulting in cancer.
      The astonishing developments in peptide and nucleic acid chemistry have opened
      the door for the development of new, highly specific probes such as antisense,
      aptamer and peptidomimetic molecules to image the oncogenes and anti-oncogenes
      transcriptional (messenger ribonucleic acid) and translational (protein) products
      involved in carcinogenesis. In this article, I shall review the basic molecular
      mechanisms of carcinogenesis and describe the molecular probes that are currently
      being developed.

PMID- 10086718
TI  - Vocal cord paralysis after 131I therapy for solitary toxic nodule.

PMID- 10086719
TI  - MIRD Pamphlet No. 15: Radionuclide S values in a revised dosimetric model of the
      adult head and brain. Medical Internal Radiation Dose.
AB  - Current dosimetric models of the brain and head lack the anatomic detail needed
      to provide the physical data necessary for suborgan brain dosimetry. During the
      last decade, several new radiopharmaceuticals have been introduced for brain
      imaging. The marked differences of these tracers in tissue specificity within the
      brain and their increasing use for diagnostic studies support the need for a more
      anthropomorphic model of the human brain and head for use in estimating regional
      absorbed dose within the brain and its adjacent structures. METHODS: A new brain
      model has been developed that includes eight subregions: the caudate nuclei, the
      cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nuclei,
      the thalami, the third ventricle and the white matter. This brain model is
      incorporated within a total revision of the head model presented in MIRD Pamphlet
      No. 5 Revised. Modifications include the addition of the eyes, the teeth, the
      mandible, an upper facial region, a neck region and the cerebrospinal fluid
      within both the cranial and spinal regions. RESULTS: Absorbed fractions of energy
      for photon and electron sources located in 14 source regions within the new model
      were calculated using the EGS4 Monte Carlo radiation transport code for particles
      in the energy range 10 keV-4 MeV. These absorbed fractions were then used along
      with radionuclide decay data to generate S values for 24 radionuclides that are
      used in clinical or investigational studies of the brain, 12 radionuclides that
      localize within the cranium and spinal skeleton and 12 radionuclides that
      selectively localize in the thyroid gland. CONCLUSION: A substantial revision to
      the dosimetric model of the adult head and brain originally published in MIRD
      Pamphlet No. 5 Revised is presented. This revision supports suborgan brain
      dosimetry for a variety of radiopharmaceuticals used in neuroimaging. Dose
      calculations for the neuroimaging agent 1231-tropane provide an example of the
      new model and yield mean brain doses that are consistent with published values.
      However, the absorbed dose to subregions within the brain such as the caudate and
      lentiform nuclei may exceed the average brain dose by a factor of up to 5.

PMID- 10086720
TI  - Infantile leukemia and soybeans--a hypothesis.
AB  - Recent molecular-genetic studies have revealed that in the majority of patients
      with secondary leukemia induced by topoisomerase II (topo II) inhibitors and also
      with infantile acute leukemia (IAL), the breakpoints are clustered within
      scaffold attachment regions (SARs) of 3'-MLL-bcr near exon 9. Genistein, abundant
      in soybeans, is reported to be a potent nonintercalative topo II inhibitor. It
      interferes with the break-reseal reaction of topo II by stabilizing a cleavable
      complex, which in the presence of detergents, results in DNA strand breaks. The
      present study revealed that genistein induced chromatid-type aberrations, in
      which chromatid exchanges are often observed. Genistein seems to act in a manner
      very similar to that of VP-16, although the latter is reported to produce both
      chromatid- and chromosome-type aberrations. In view of this pharmacological
      similarity between genistein and VP-16, and also the similarity of breakpoint
      clustering regions within the MLL gene in reported cases with secondary leukemia
      and IAL, genistein may be largely responsible for the development of IAL.

PMID- 10086721
TI  - Post-transplant acute myeloid leukemia (PT-AML).
AB  - Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event
      with only a few published cases in the literature. We present three patients who
      developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation.
      Molecular analysis detected a t(9;11) in one patient and documented the recipient
      origin of AML in a second patient. All patients were treated with chemotherapy.
      Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two
      patients and to prednisone alone in one patient. Two patients achieved a complete
      remission (CR), with a remission duration of 4.6 months in one patient, the other
      patient died from septicemia after 15.2 months in CR. One patient was refractory
      to chemotherapy and died from septicemia. This report together with the
      documented cases in the literature suggests that PT-AML (1) develops after a
      median interval of 5 years after transplantation with variable latency (range, <1
      17 years); (2) is heterogeneous with respect to FAB classification; (3) shows
      chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8,
      11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of
      immunosuppression and produces a CR rate of 56% with a median remission duration
      of 4.6 months and an overall survival of 2.6 months; (5) the major complications
      are early death (25%), gram-negative septicemia, progressive disease or relapse.
      This review provides diagnostic and therapeutic experiences and guidelines for
      the management of this increasing group of post-transplant patients.

PMID- 10086722
TI  - Polycythemia vera megakaryocytes but not megakaryocytes from normal controls and
      patients with smokers polyglobuly spontaneously express IL-6 and IL-6R and
      secrete IL-6.
AB  - Polycythemia rubra vera (PV) represents a clonal hematological disorder defined
      by an abnormal expansion of erythroid precursors and megakaryopoiesis, in
      particular. Ample evidence has been provided that the IL-6/1L-6R complex may be
      responsible for the proliferation of normal and neoplastic megakaryocytes in
      vitro and this fact lead us to the hypothesis, that defects in the regulation of
      IL-6 synthesis take part in the pathogenesis of PV. The study was carried out to
      determine the IL-6 serum levels and the megakaryocytic IL-6 production in
      patients with PV and to compare these data with the situation in hematologically
      healthy donors as well as in patients suffering from spurious polycythemia-
      smokers polyglobuly (PG). For this purpose, IL-6 serum levels were measured by
      ELISA and the megakaryocytic production studied by immunohistochemistry, reverse
      hemolytic plaque assay (RHPA) together with reverse transcription/polymerase
      chain reaction (RT-PCR) in highly enriched megakaryocyte preparations. In
      additional experiments, the influence of IL-3 stimulation and the expression of
      IL-6R were tested. Serum levels of IL-6 did not differ between the three groups
      under study. In contrast, immunohistochemistry revealed a raised proportion of
      megakaryocytes expressing IL-6 in PV as compared to normal donors and patients
      suffering from PG. The percentage of megakaryocytes actively secreting this
      cytokine as detected by the RHPA was 20 times greater than in both the other
      groups. This phenomenon was further substantiated by the fact that IL-6 mRNA
      could only be shown in PV megakaryocyte preparations. The regulation of IL-6
      secretion appears to be abnormal in PV. Whereas in the normal and in the PG group
      IL-3 stimulation exerts a marked increase in megakaryocytic IL-6 secretion, PV
      megakaryocytes responded with a paradoxical down-regulation of IL-6 synthesis
      combined with the loss of IL-6R. Our data describe for the first time an
      abnormally raised IL-6 production by PV megakaryocytes and point towards
      fundamental regulatory alterations of the IL-6 synthesis in this disease.

PMID- 10086723
TI  - Intensive high-dose asparaginase consolidation improves survival for pediatric
      patients with T cell acute lymphoblastic leukemia and advanced stage
      lymphoblastic lymphoma: a Pediatric Oncology Group study.
AB  - This study was designed to test the hypothesis that high-dose asparaginase
      consolidation therapy improves survival in pediatric patients with T cell acute
      lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred
      and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia
      (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled
      in POG study 8704 (T-3). Treatment included rotating combinations of high-dose
      myelosuppressive chemotherapy agents proven to be effective in T cell ALL in
      other POG group-wide or local institutional protocols (including vincristine,
      doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine
      and mercaptopurine). After achieving a complete remission (CR), patients were
      randomized to receive or not receive high-dose intensive asparaginase
      consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular
      injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine)
      was given to prevent CNS disease, and CNS irradiation was used only for patients
      with leukemia and an initial WBC of >50,000/microl or patients with active CNS
      disease at diagnosis. CR was achieved in 96% of patients. The high-dose
      asparaginase regimen was significantly superior to the control regimen for both
      the leukemia and lymphoma subgroups. Four-year continuous complete remission rate
      (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared
      to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%)
      with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided
      logrank test had a P value <0.001 favoring asparaginase, while corresponding
      values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities
      were tolerable, but there were 18 failures due to secondary malignancies (16 with
      non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia
      patients) nor lymphoma stage were major prognostic factors. We conclude that when
      added to a backbone of effective rotating agents, repeated doses of asparaginase
      during early treatment improve the outcome for patients with T cell leukemia and
      advanced stage lymphoblastic lymphoma.

PMID- 10086724
TI  - Phase I trial of sequential topotecan followed by etoposide in adults with
      myeloid leukemia: a National Cancer Institute of Canada Clinical Trials Group
      Study.
AB  - Prolonged exposure to a topoisomerase I inhibitor may increase expression of
      topoisomerase II, making cells more susceptible inhibitors of that enzyme. This
      study was undertaken to establish the maximum tolerated dose (MTD) of a
      topotecan/topoisomerase II inhibitor sequential combination that may be active in
      acute leukemia, and to evaluate the effects of in vivo exposure to topotecan on
      topoisomerase II levels in leukemic blast cells as measured by image cytometry.
      Patients who were eligible for this phase I study had relapsed or refractory
      acute myeloid leukemia (< or = 2 prior regimens) or CML blast crisis (0 or 1
      prior regimen). Topotecan was given as a 5 day continuous i.v. infusion and was
      to be escalated through three levels (1.5, 1.75 and 2.0 mg/m2 day), followed by
      etoposide at two dose levels (100 and 150 mg/m2) i.v. bolus days 6, 7 and 8.
      Topoisomerase IIalpha levels in leukemic blasts from bone marrow were measured by
      image cytometry prior to starting treatment, on day 5 of topotecan infusion and
      on day 28; and daily during topotecan in peripheral blood blasts. Dose-limiting
      toxicity was seen in two of six patients at the first dose level (topotecan 1.5
      mg/m2/day, etoposide 100 mg/m2/day; > or = grade 3 mucositis in both cases). This
      cohort was expanded to 10 patients; no further non-hematologic dose-limiting
      toxicity was observed, but given the extent of toxicity seen, further dose
      escalation was judged not to be feasible. Topo IIalpha levels increased in
      peripheral blood blasts during the first 72 h of topotecan infusion and returned
      to near baseline by day 5, whereas levels appeared to decrease in bone marrow
      blasts by day 5 compared to pretreatment. One complete hematologic and
      cytogenetic remission in a patient with CML blast crisis was observed in the 10
      patients evaluable for response. The sequential administration of topotecan 1.5
      mg/m2/day continuous infusion for 5 days followed by etoposide 100 mg/m2/day x 3
      is the recommended phase II dose for this schedule. Topotecan increases topo
      IIalpha expression in vivo in leukemia cells, but levels of the enzyme are cell
      cycle dependent. Pharmacodynamic evaluation of the sequential or combination
      administration of novel antileukemic agents may help improve treatment strategies
      in acute leukemia.

PMID- 10086725
TI  - MDS1/EVI1 enhances TGF-beta1 signaling and strengthens its growth-inhibitory
      effect but the leukemia-associated fusion protein AML1/MDS1/EVI1, product of the
      t(3;21), abrogates growth-inhibition in response to TGF-beta1.
AB  - MDS1/EVI1, located on chromosome 3 band q26, encodes a zinc-finger DNA-binding
      transcription activator not detected in normal hematopoietic cells but expressed
      in several normal tissues. MDS1/EVI1 is inappropriately activated in myeloid
      leukemias following chromosomal rearrangements involving band 3q26. The
      rearrangements lead either to gene truncation, and to expression of the
      transcription repressor EVI1, as seen in the t(3;3)(q21;q26) and inv(3)(q21q26),
      or to gene fusion, as seen in the t(3;21)(q26;q22) which results in the fusion
      protein AML1/MDS1/EVI1. This fusion protein contains the DNA-binding domain of
      the transcription factor AML1 fused in-frame to the entire MDS1/EVI1 with the
      exclusion of its first 12 amino acids. In this report, we have analyzed the
      response of the hematopoietic precursor cell line 32Dcl3, expressing either the
      normal protein MDS1/EVI1 or the fusion protein AML1/MDS1/EVI1, to factors that
      control cell differentiation or cell replication. The 32Dcl3 cells are IL-3
      dependent for growth and they differentiate into granulocytes when exposed to G
      CSF. They are growth-inhibited by TGF-beta1. We show that whereas the expression
      of MDS1/EVI1 has no effect on granulocytic differentiation induced by G-CSF,
      expression of AML1/MDS1/EVI1 blocks differentiation resulting in cell death. This
      effect is similar to that previously described by others for 32Dcl3 cells that
      express transgenic Evil. Furthermore, we show that whereas the expression of the
      fusion protein AML1/MDS1/EVI1 completely abrogates the growth-inhibitory effect
      of TGF-beta1 and allows 32Dcl3 cells to proliferate, expression of the normal
      protein MDS1/EVI1 has the opposite effect, and it strengthens the response of
      cells to the growth-inhibitory effect of TGF-beta1. By using the yeast two-hybrid
      system, we also show that EVI1 (contained in its entirety in MDS1/EVI1 and
      AML1/MDS1/EVI1) physically interacts with SMAD3, which is an intracellular
      mediator of TGF-beta1 signaling. Finally, we have correlated the response of the
      cells to G-CSF or TGF-beta1 with the ability of the normal and fusion proteins to
      activate or repress promoters which they can directly regulate by binding to the
      promoter site. We propose that mutations of MDS1/EVI1 either by gene truncation
      resulting in the transcription repressor EVI1 or by gene fusion to AML1 lead to
      an altered cellular response to growth and differentiation factors that could
      result in leukemic transformation. The different response of myeloid cells
      ectopically expressing the normal or the fusion protein to G-CSF and TGF-beta1
      could depend on the different transactivation properties of these proteins
      resulting in divergent expression of downstream genes regulated by the two
      proteins.

PMID- 10086726
TI  - Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality.
AB  - In de novo t(8;21) AML which shows terminal neutrophilic differentiation, the BCL
      2 expression was found to be significantly lower than that in types of other AML
      regardless of the phenotypic differentiation status. An inverse correlation
      between BCL-2 expression and the S/G2/M population cells was observed in AML. The
      S/G2/M population in t(8;21)AML was larger than in the other types of AML. In
      t(8;21)AML, spontaneous apoptosis after a 12-h liquid culture was prominent, and
      the autonomous DNA synthesis after a 72-h liquid culture was low. G-CSF and IL-5
      promoted the colony formation of t(8;21)AML cells. The data suggest that, in
      vivo, the low BCL-2 in t(8;21)AML induced entry of cells from the G0/G1 phase to
      S phase, but the cells easily die by apoptosis, in vitro. The low BCL-2
      expression and the supportive effects of G-CSF and IL-5 in t(8;21)AML is thought
      to be a key phenomenon which might be related to the formation of the in vivo
      blood picture, such as prominent neutrophilic differentiation and eosinophilia.
      Cellular extracts from t(8;21)AML cell line Kasumi-1 bound to both the AML1 and
      CRE binding sites in the bcl-2 promoter, but none of the cellular extracts from
      de novo t(8;21)AML bound to either of these sites. The DNA binding activity of
      transactivators in de novo t(8;21)AML is different from that in Kasumi-1 cells
      probably due to the phosphorylation status.

PMID- 10086727
TI  - Identification of a novel molecular partner of the E2A gene in childhood
      leukemia.
AB  - The 'promiscuous' E2A gene, at 19p13.3, is fused with two different molecular
      partners, PBX1 and HLF, following two chromosome translocations recurrent in
      childhood pre-B ALL. We have identified a novel gene, FB1, by virtue of its
      fusion with E2A and by a combination of molecular techniques. FB1 was localized
      on 19q13.4, suggesting that the novel chimera originated by a cryptic
      rearrangement of chromosome 19. Two FB1 transcripts, of 1.2 kb and 1.1 kb, are
      differentially expressed at low level in a variety of human tissues, including
      hemopoietic cell lines from different lineages. Accordingly, FB1 cDNA displays
      high homology with a number of cDNA clones from different human tissues. High
      homology was found also with cDNA clones from mouse and rat, suggesting that the
      sequence might be conserved at least among mammals. The function of the putative
      FB1 protein, however, is currently unknown as database sequence comparisons have
      failed to reveal strong homology with known proteins. The E2A/FB1 fusion appears
      to be a recurrent feature of pre-B ALLs, suggesting that it might have a role in
      the development and/or progression of leukemogenesis.

PMID- 10086728
TI  - Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid
      leukemia associated with complete or partial monosomy 7. European Working Group
      on MDS in Childhood (EWOG-MDS).
AB  - We reviewed the clinical features, treatment, and outcome of 100 children with
      myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), and
      acute myeloid leukemia (AML) associated with complete monosomy 7 (-7) or deletion
      of the long arm of chromosome 7 (7q-). Patients with therapy-induced disease were
      excluded. The morphologic diagnoses according to modified FAB criteria were: MDS
      in 72 (refractory anemia (RA) in 11, RA with excess of blasts (RAEB) in eight,
      RAEB in transformation (RAEB-T) in 10, JMML in 43), and AML in 28. The median age
      at presentation was 2.8 years (range 2 months to 15 years), being lowest in JMML
      (1.1 year). Loss of chromosome 7 as the sole cytogenetic abnormality was observed
      in 75% of those with MDS compared with 32% of those with AML. Predisposing
      conditions (including familial MDS/AML) were found in 20%. Three-year survival
      was 82% in RA, 63% in RAEB, 45% in JMML, 34% in AML, and 8% in RAEB-T. Children
      with -7 alone had a superior survival than those with other cytogenetic
      abnormalities: this was solely due to a better survival in MDS (3-year survival
      56 vs 24%). The reverse was found in AML (3-year survival 13% in -7 alone vs 44%
      in other cytogenetic groups). Stable disease for several years was documented in
      more than half the patients with RA or RAEB. Patients with RA, RAEB or JMML
      treated with bone marrow transplantation (BMT) without prior chemotherapy had a 3
      year survival of 73%. The morphologic diagnosis was the strongest prognostic
      factor. Only patients with a diagnosis of JMML fitted what has previously been
      referred to as the monosomy 7 syndrome. Our data give no support to the concept
      of monosomy 7 as a distinct syndrome.

PMID- 10086729
TI  - Clonal chromosomal abnormalities in the stem cell compartment of patients with
      acute myeloid leukemia in morphological complete remission.
AB  - Acute myeloid leukemia arises from the clonal expansion of a malignant
      transformed progenitor cell. Despite intensive chemotherapy, final disease
      eradication is achieved by a small proportion of cases only and 50-70% of adults
      with AML will ultimately relapse and die from their disease. Hence residual
      disease below the level of morphological detectability must be assumed in
      clinical and morphological complete remission. CD34+/CD38- and CD34+/CD38+
      subpopulations of seven patients in morphological complete remission were
      isolated by FACS (purity >98%) and were analyzed by conventional cytogenetics or
      FISH for chromosomal aberrations. In five of seven patients, clonal chromosomal
      abnormalities were detected in the CD34+/CD38+ subpopulation and in one patient
      with AML M2 (add (2)(q37)) in the most immature CD34+/CD38- stem cell
      compartment. One patient with AML M4Eo (inv(16),+8), showed a normal karyotype by
      conventional cytogenetic analysis, whereas four of 15 metaphases of the sorted
      CD34+/CD38+ subpopulation revealed the inversion 16. These observations underline
      that leukemic cells can survive intensive chemotherapy in the niche of the stem
      cell compartment. In some patients the sensitivity for the detection of
      persistent leukemic cells seems to be higher in FACS-sorted subpopulations than
      conventional cytogenetic analysis of the unseparated bone marrow.
      Immunophenotyping revealed minimal residual disease in four of the patients.
      Functional analysis has to be performed to investigate the leukemogenic potential
      of these residual cells.

PMID- 10086730
TI  - The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression
      of myelodysplastic syndromes.
AB  - The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1
      expression levels were examined for 57 patients with myelodysplastic syndromes
      (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in
      transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with
      acute myeloid leukemia (AML) evolved from MDS. These levels significantly
      increased in proportion to the disease progression of MDS from RA to overt AML
      via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1
      expression levels in PB significantly correlated with the evolution of RAEB or
      RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were
      superior to those in BM for early prediction of the evolution to AML by means of
      quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of
      patients with overt AML evolved from MDS was significantly decreased by effective
      chemotherapy or allogeneic stem cell transplantation and became undetectable in
      long-term survivors. These results clearly showed that WT1 expression levels are
      a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect
      the disease progression of MDS. Therefore, monitoring of WT1 expression levels
      has made continuous assessment of the disease progression of MDS possible, as
      well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6
      months. The results also showed that quantitation of WT1 expression levels is
      useful for diagnosis of minimal residual disease of MDS with high sensitivity,
      thus making it possible to evaluate the efficacy of treatment for MDS.

PMID- 10086731
TI  - Chemotherapeutic drugs sensitize pre-B ALL cells for CD95- and cytotoxic T
      lymphocyte-mediated apoptosis.
AB  - The CD95 (APO-1/Fas) system plays an important role in lymphocyte homeostasis and
      contributes to anticancer drug-induced apoptosis in some tumor cells. Most
      childhood B-lineage ALL cells are constitutively resistant towards CD95-induced
      death. We report here that chemotherapeutic drugs, such as doxorubicin,
      cytarabine, methotrexate and 6-mercaptopurine, sensitize CD95-resistant pre-B-ALL
      cell lines for CD95- and lymphokine-activated killer (LAK)-induced cell death.
      Enhanced susceptibility in drug-treated cells was found to be associated with
      increased expression of CD95 mRNA and surface expression of CD95 protein, as well
      as loss of Bcl-xL protein and disturbance of mitochondrial function. Low level
      activation of caspases and cleavage of poly(ADP-ribose) polymerase following CD95
      triggering was strongly increased in drug pre-treated cells. Furthermore, drug
      pre-treated cells could be rescued from CD95-mediated apoptosis by blocking the
      CD95-signaling pathway with a FADD-dominant negative expression construct. Our
      data suggest that chemotherapeutic drugs may sensitize pre-B ALL cells by at
      least two mechanisms: (1) by increasing CD95 expression; and (2) by lowering the
      threshold for apoptotic signals. These findings may explain the effectiveness of
      low-dose chemotherapy and indicate an active role for key molecules of apoptosis
      and the immune system during chemotherapy of leukemia.

PMID- 10086732
TI  - Decreased sensitivity of drug-resistant cells towards T cell cytotoxicity.
AB  - Killing of target cells by cytotoxic T cells is mediated by induction of
      apoptosis requiring functional death pathways. Kill is mediated either by the
      CD95 or the perforin/granzyme pathway. We found that SH-EP neuroblastoma cells
      are preferentially killed via CD95, while in the T leukemia cell line CEM CD95
      and perforin/granzyme are involved. In both types of cell lines, cells resistant
      to CD95- and drug-induced apoptosis are crossresistant to cytotoxic T cell kill.
      Resistant cells show decreased apoptosis and deficient activation of caspases
      indicated by decreased cleavage of the prototype caspase substrate PARP.
      Preincubation with the caspase inhibitor zVAD-fmk strongly decreased LAK cell
      kill in sensitive cells. Although parental CEM cells could be sensitized for LAK
      kill by preincubation with doxorubicin, resistance could not be reverted in
      doxorubicin or CD95 resistant CEM cells. These data demonstrate the
      crossresistance in induction of apoptosis by different cytotoxic regimens in
      tumor cells and may have implications for the immunotherapy of tumors in which
      apoptosis resistance was induced by previous chemotherapy.

PMID- 10086733
TI  - Flow cytometric analysis of normal B cell differentiation: a frame of reference
      for the detection of minimal residual disease in precursor-B-ALL.
AB  - During the last two decades, major progress has been made in the technology of
      flow cytometry and in the availability of a large series of monoclonal antibodies
      against surface membrane and intracellular antigens. Flow cytometric
      immunophenotyping has become a diagnostic tool for the analysis of normal and
      malignant leukocytes and it has proven to be a reliable approach for the
      investigation of minimal residual disease (MRD) in leukemia patients during and
      after treatment. In order to standardize the flow cytometric detection of MRD in
      acute leukemia, a BIOMED-1 Concerted Action was initiated with the participation
      of six laboratories in five different European countries. This European co
      operative study included the immunophenotypic characterization and enumeration of
      different precursor and mature B cell subpopulations in normal bone marrow (BM).
      The phenotypic profiles in normal B cell differentiation may form a frame of
      reference for the identification of aberrant phenotypes of precursor-B cell acute
      lymphoblastic leukemias (precursor-B-ALL) and may therefore be helpful in MRD
      detection. Thirty-eight normal BM samples were analyzed with five different pre
      selected monoclonal antibody combinations: CD10/CD20/CD19, CD34/CD38/CD19,
      CD34/CD22/CD19, CD19/CD34/CD45 and TdT/CD10/CD19. Two CD19- immature
      subpopulations which coexpressed B cell-associated antigens were identified:
      CD34+/CD22+/CD19- and TdT+/CD10+/CD19-, which represented 0.11 +/- 0.09% and 0.04
      +/- 0.05% of the total BM nucleated cells, respectively. These immunophenotypes
      may correspond to the earliest stages of B cell differentiation. In addition to
      these minor subpopulations, three major CD19+ B cell subpopulations were
      identified, representing three consecutive maturation stages;
      CD19dim/CD34+/TdT+/CD10bright/CD22dim/CD45dim /CD38bright/CD20- (subpopulation
      1), CD19+/CD34-/TdT-/CD10+/CD22dim/CD45+/CD38bright/ CD20dim (subpopulation 2)
      and CD19+/CD34-/TdT-/CD10-/CD22bright/CD45bright/ CD38dim/CD20bright
      (subpopulation 3). The relative sizes of subpopulations 1 and 2 were found to be
      age related: at the age of 15 years, the phenotypic precursor-B cell profile in
      BM changed from the childhood 'immature' profile (large subpopulations 1 and
      2/small subpopulation 3) to the adult 'mature' profile (small subpopulation 1 and
      2/large subpopulation 3). When the immunophenotypically defined precursor-B cell
      subpopulations from normal BM samples are projected in fluorescence dot-plots,
      templates for the normal B cell differentiation pathways can be defined and so
      called 'empty spaces' where no cell populations are located become evident. This
      allows discrimination between normal and malignant precursor-B cells and can
      therefore be used for MRD detection.

PMID- 10086734
TI  - Bone morphogenetic protein 9 is a potent synergistic factor for murine
      hemopoietic progenitor cell generation and colony formation in serum-free
      cultures.
AB  - The effect of the recently cloned cytokine bone morphogenetic protein 9 (BMP-9)
      on colony formation and generation in vitro clonable hematopoietic progenitors
      (CFU-C) in serum-free liquid cultures (LC) of both normal and post-5-fluorouracil
      murine bone marrow cells was studied in the presence of various other cytokines.
      In LC, BMP-9 concentrations of 100 ng or more per ml led to complete inhibition
      of Steel Factor (SF) + interleukin-11 (IL-11) or IL-12 supported CFU-C
      generation, which was partly abrogated when IL-3 was additionally included. We
      found this inhibitory effect of BMP-9 to be mediated by an increased TGF-beta1
      elaboration and TGF-beta1 mRNA expression in bone marrow cells with increasing
      BMP-9 concentrations. In the presence of neutralizing antibodies (Ab) against TGF
      beta1, BMP-9 concentrations of 3 ng or higher synergized with IL-3, SF+IL-3,
      SF+IL-11/12, or IL-3+SF+IL-11/12 to increase CFU-C generation. Similarly, high
      BMP-9 concentrations dramatically inhibited primary colony formation induced by
      SF+IL-11/12, whereas in the presence of TGF-beta1 neutralizing Ab only 3 ng or
      more BMP-9 per ml stimulated both the time of colony appearance, the colony size
      and colony numbers in the presence of IL-3, M-CSF, GM-CSF, SF, SF+Flt3-L, SF+IL
      3, SF+IL-11/12 or IL-3+SF+IL-11/12. BMP-9 neither stimulated CFU-C generation nor
      colony formation as a single factor, nor did it synergize with thrombopoietin
      (Tpo), erythropoietin (Epo), Flt3-L, IL-11, IL-12 or G-CSF. The effect of BMP-9
      on its target cells was direct as demonstrated using single-sorted stem cells.
      These observations demonstrate that BMP-9 plays a dual role in regulating
      proliferation of primitive hemopoietic progenitor cells. Thus, in addition to its
      ability to enhance TGF-beta1 elaboration in bone marrow cells, it acts as a
      potent synergistic activity that is different from SF, Flt3-L, IL-11 or IL-12.
      BMP-9 mRNA was exclusively detected in the liver of adult mice, whilst no
      expression was found in stromal cell lines propagated from day-16 fetal liver or
      neonatal or adult bone marrow. 125I-BMP-9 bound specifically to a high percentage
      of blast cells in lineage-depleted post-fluorouracil bone marrow cells and to
      megakaryocytes in normal and post-fluorouracil bone marrow, indicating that BMP
      9R are expressed on these cells. The dissociation between the site of BMP-9
      production and its target cells in the bone marrow makes BMP-9 a hemopoietic
      hormone.

PMID- 10086735
TI  - Ex vivo manipulations alter the reconstitution potential of mobilized human CD34+
      peripheral blood progenitors.
AB  - The phenotype and functions of CD34+ cells isolated from peripheral blood (PB) of
      steady-state healthy volunteers (ssPB-CD34), and of patients or healthy
      volunteers after mobilization (mPB-CD34) were investigated. ssPB-CD34+ cells
      contain a lymphoid cell population that co-express T or B cell markers, while mPB
      CD34+ cells lack this population. After 5-day culture, significantly higher
      levels of expansion in cell, CD34+ cell, and HPP-CFC numbers were induced in ssPB
      CD34+ cells, as compared to mPB-CD34+ cells. Hematopoietic reconstitution
      potential of these ex vivo manipulated CD34+ PBPC was evaluated in SCID-hu mice.
      It was found that ssPB-CD34+ cells retained the potential to reconstitute human
      bone marrow (BM), as well as thymus implanted in SCID animals. In contrast, only
      very low levels of reconstitution were detected in human hematopoietic tissues
      injected with cultured mPB-CD34+ cells. Reconstitution was restricted to myeloid
      cells, and no B cell reconstitution in bone marrow, or T cell reconstitution in
      thymus was achieved by these cells. The loss of B cell reconstitution potential
      of mPB-CD34+ cells was shown to be induced in a time-dependent manner during
      culture. These results indicate that mPB-CD34+ cells have different phenotypic
      and functional properties from ssPB-CD34+ cells. This may affect the efficacy of
      cell and gene therapy with mobilized PBPC.

PMID- 10086736
TI  - Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent
      in diffuse large B cell lymphoma.
AB  - The two gene products of the CDKN2A gene, p16 and p19ARF, have recently been
      linked to each of two major tumour suppressor pathways in human carcinogenesis,
      the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the
      retinoblastoma gene product by cyclin D-dependent kinases, whereas p19ARF targets
      MDM2, a p53 inhibitory protein, for degradation. A deletion of CDKN2A would
      therefore disturb both pathways. To explore the p53 pathway genes as a functional
      unit in diffuse large B cell non-Hodgkin's lymphomas (DLCL), we wanted to see
      whether there exists mutually exclusiveness of aberrations of CDKN2A, MDM2 and
      p53, since this has not been analysed previously. We investigated 37 DLCL for
      aberrations of p15, p16, p19ARF, MDM2, and p53 at the epigenetic, genetic and/or
      protein levels. Homozygous deletion of CDKN2A was detected in seven (19%) of 37
      tumours, and another three cases were hypermethylated at the 5' CpG island of
      p16. No point mutations were found in CDKN2B or CDKN2A. Immunohistochemical
      staining of formalin-fixed, paraffin-embedded tissue for p16 confirmed these
      results, as all tumours with alterations of CDKN2A were p16 immunonegative. We
      found p53 mutations in eight (22%) cases and MDM2 overexpression in 16 (43%)
      tumours. Twenty-three (62%) tumours had alterations of one or more p53 pathway
      components (p53, p19ARF and MDM2). Furthermore, 7/9 (78%) p16-immunonegative
      tumours showed co-aberration of p53 and/or MDM2. The lack of correlation between
      these aberrations suggests that DLCL acquire additional growth advantage by
      inactivating both of these critical regulatory pathways.

PMID- 10086737
TI  - Translocations involving the short arm of chromosome 17 in chronic B-lymphoid
      disorders: frequent occurrence of dicentric rearrangements and possible
      association with adverse outcome.
AB  - Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor
      suppressor gene localizes, are rarely described in chronic lymphocytic leukemia
      and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic
      techniques have indicated a significant incidence of TP53 deletions, suggesting
      the involvement of chromosome 17p in these disorders. By conventional karyotype,
      we have identified unbalanced translocations involving 17p in 14 out of 123 (11%)
      CLL/SLL patients with clonal abnormalities. Cases were characterized by
      resistance to chemotherapy and a poor clinical outcome. The karyotypes presented
      a high incidence of complex rearrangements and 17p translocations were
      characterized by various partners. In 10 cases a centric fusion was assessed by
      fluorescent in situ hybridization (FISH) experiments using specific centromeric
      probes. The incidence of dicentric translocations in these series is therefore
      significantly higher than usually described, arising in up to 71% (10 out of 14
      cases). In all cases, translocations led to a monosomy 17p and to a TP53
      monoallelic deletion. The adverse clinical outcome confirms that structural
      abnormalities involving chromosome 17p are associated with disease progression in
      patients with chronic lymphoproliferative disorders.

PMID- 10086738
TI  - Bone marrow angiogenesis in patients achieving complete response after stem cell
      transplantation for multiple myeloma.
AB  - Although most of the initial studies in angiogenesis were done on solid tumors,
      there is now data suggesting the importance of angiogenesis in hematologic
      malignancies. We estimated bone marrow microvessel density before autologous stem
      cell transplantation and at the time of response in 13 patients with myeloma
      (seven complete and six partial responders) using an immunohistochemical stain
      for factor VIII-related antigen (von Willebrand factor). Baseline microvessel
      density was significantly different between bone marrow samples from patients
      with myeloma and morphologically normal, staging marrows from patients with
      limited stage Hodgkin's disease, mean (+/- s.d.) 294 (+/-115)/mm2 vs 93 (+/
      26/mm2, respectively, P = 0.001. After transplantation, microvessel density
      continued to be high in myeloma samples compared to samples from control patients
      with limited stage Hodgkin's disease, mean (+/- s.d.) 230 (+/-68)/mm2, P = 0.003.
      There was no difference in microvessel density at the time of complete or partial
      response compared to values prior to transplantation. This report confirms that
      increased angiogenesis is found in myeloma bone marrow prior to transplantation,
      and suggests that increased angiogenesis persists even after complete response.

PMID- 10086739
TI  - Interferon-alpha protects myeloma cell lines from dexamethasone-induced
      apoptosis.
AB  - Because of the increasing use of IFN-alpha in both induction and maintenance
      therapy for multiple myeloma (MM), its effect on growth and apoptosis of myeloma
      cells is important to consider. To investigate the role of IFN-alpha on the
      growth of myeloma cells, we have studied its effects on the response of
      interleukin 6 (IL-6)-dependent myeloma cell line (ANBL6) and IL-6-independent
      myeloma cell line (C2E3) in the presence of IL-6 and dexamethasone (Dex). We
      found that although IFN-alpha is a potent inhibitor of proliferation, it has only
      a minimal effect on induction of apoptosis. Moreover, we found IFN-alpha as well
      as IL-6 can significantly suppress dexamethasone-induced apoptosis. The
      suppression of apoptosis is concurrent with the induction of both AP-1 and STAT
      binding activity. We also found that IL-6 but not IFN-alpha up-regulates Bcl-X(L)
      expression. However, IL-6-mediated Bcl-X(L) expression is suppressed in the
      presence of Dex. Therefore, the expression of Bcl-X(L) does not account for the
      protection of Dex-induced apoptosis by IFN-alpha and IL-6. Taken together, our
      results suggest that IFN-alpha may counteract the beneficial effects of
      corticosteroids or perhaps other apoptosis inducing agents in the treatment of
      myeloma.

PMID- 10086740
TI  - TEL-AML1 fusion transcript designates a favorable outcome with an intensified
      protocol in childhood acute lymphoblastic leukemia.

PMID- 10086741
TI  - Low-grade MALT lymphoma mimicking Waldenstrom's macroglobulinemia.

PMID- 10086742
TI  - Immunoglobulin lambda chain gene rearrangement in a case of acute
      nonlymphoblastic leukemia.

PMID- 10086743
TI  - A novel t(Y;11) translocation with MLL gene rearrangement in a case of acute
      myelomonocytic leukemia (AML-M4)

PMID- 10086744
TI  - Ineffectiveness of pulmonary irradiation in the treatment of leukemic blast
      crisis.

PMID- 10086745
TI  - Lack of efficacy of clarithromycin in advanced multiple myeloma. Intergroupe
      Francais du Myelome (IFM)

PMID- 10086746
TI  - Trisomy 8 as a secondary genetic change in acute megakaryoblastic leukemia
      associated with Down's syndrome.

PMID- 10086747
TI  - Acute promyelocytic leukemia in a patient with idiopathic myelofibrosis.

PMID- 10086748
TI  - In vitro development of haemopoietic progenitors in myelodysplastic syndromes
      (MDS)

PMID- 10086749
TI  - Inaccuracy and vested interests--two threats to etiologic research.

PMID- 10086750
TI  - Persistent polyclonal lymphocytosis (PPLB)

PMID- 10086751
TI  - Behavior therapy for urge incontinence in older women.

PMID- 10086752
TI  - Aspirin and the risk of hemorrhagic stroke.

PMID- 10086753
TI  - Intranasal steroids or antihistamines for allergic rhinitis?

PMID- 10086754
TI  - Antibiotics for acute bronchitis: a meta-analysis.

PMID- 10086755
TI  - Horse-chestnut seed extract for chronic venous insufficiency.

PMID- 10086756
TI  - Treating Helicobacter pylori infection in nonulcer dyspepsia.

PMID- 10086757
TI  - Gabapentin for painful diabetic neuropathy.

PMID- 10086758
TI  - Comparing epidural and parenteral opioid analgesia during labor.

PMID- 10086759
TI  - Shared care: what mix of generalist and specialist care optimizes patient
      outcomes?

PMID- 10086760
TI  - Concurrent treatment of patients with depression in the community: provider
      practices, attitudes, and barriers to collaboration.
AB  - BACKGROUND: In randomized controlled trials, patients with major depression who
      receive broad-based collaborative treatment by both primary care physicians
      (PCPs) and mental health providers (MHPs) have better outcomes than patients who
      receive usual care. However, little is known about the concurrent treatment of
      patients with depression in the community. This study describes the perceptions
      of PCPs of the frequency of concurrent treatment in community settings, the
      degree of collaboration between co-treating providers, and factors associated
      with greater interaction and collaboration. METHODS: A survey was distributed to
      a stratified, random sample of 276 eligible family physicians in Michigan.
      Primary analyses were descriptive statistics (point estimation) of PCP practice
      patterns. Secondary analyses explored predictors of collaboration with
      multivariable regression. RESULTS: A total of 162 eligible PCPs (59%) returned
      the survey. PCPs reported that they co-treated approximately 30% of their
      depressed patients with MHPs. They made contact with co-treating MHPs in
      approximately 50% of shared cases; however, provider contact seldom included
      joint treatment planning. PCPs perceived collaborative treatments to be more
      problematic when patients were enrolled in managed care programs. In
      multivariable regression, co-location of MHP and PCP practices (in the same
      building) was strongly associated with increased interaction and collaboration (P
      <.001). CONCLUSIONS: Concurrent treatment of depressed patients is common in the
      community, but these treatments are less interactive and collaborative than the
      treatment models proven effective in randomized controlled trails. If concurrent
      treatments are to become more collaborative-with regular contact and effective
      communication-co-location of practices appears important.

PMID- 10086761
TI  - Comanagement of patients with congestive heart failure by family physicians and
      cardiologists: frequency, timing, and patient characteristics.
AB  - BACKGROUND: Many patients with congestive heart failure (CHF) receive care solely
      from a primary care physician, while some receive care from both a primary care
      physician and a cardiologist. Patients in the latter type of care relationships
      have not been described. The principal objectives of our study were to determine
      what percentage of patients with CHF are comanaged, the characteristics of
      comanaged CHF patients, and when in the natural history of CHF this relationship
      is initiated. METHODS: A retrospective record review was conducted of all
      patients who met the modified Framingham criteria for the diagnosis of CHF in a
      large community-based family practice office. Comanagement was defined as an
      ongoing relationship with a cardiologist characterized by a minimum of one visit
      to the cardiologist's office in the year of evaluation. We divided the natural
      history of CHF into 4 stages to describe the timing of the initial referral to
      the cardiologist: I Prediagnosis; II Diagnosis; III Progression; and IV Terminal.
      RESULTS: Of 151 patients identified with CHF, 36% of the patients were comanaged
      by a primary care physician and a cardiologist. The comanagement relationship
      often began early in the development of CHF, 20% at stage I and 54% at stage II.
      The patients who were comanaged were younger, predominately men, had a greater
      frequency of myocardial infarction, were more likely to have decreased systolic
      function, were on more cardiac medications, and had fewer hospitalizations for
      CHF exacerbations compared with CHF patients managed solely by family physicians.
      CONCLUSIONS: Comanagement of patients with CHF is a common occurrence, and
      comanaged CHF patients have distinct characteristics from those managed solely by
      family physicians. These results have implications for the quality and cost of
      caring for patients with CHF and suggest that more detailed study is required.

PMID- 10086762
TI  - Extending patient care office hours: what factors are important to consider?
AB  - BACKGROUND: Primary care physicians are feeling increasing pressure to see more
      ambulatory patients each day, and most practices are considering expanded hours.
      The goal of this study was to identify factors that physicians and office
      personnel felt were important to consider when deciding whether to extend patient
      care office hours. METHODS: We used a qualitative descriptive study design with
      focus groups to elicit responses from office personnel. We recorded and
      transcribed unstructured interviews and used an editing style of data analysis to
      identify important factors. We then categorized the factors and compared them
      with the transcripts to identify which personnel groups considered each category
      of factors important. RESULTS: Eight categories of factors emerged from the focus
      group discussions. Some factors were common to more than one category. The most
      important categories were: defining the purpose of this schedule change
      (addressing specific office needs); impact on the quality of resident education;
      disruption of complex office schedules; and impact on time outside the office,
      and the potential disruption of the balance between personal and professional
      commitments. CONCLUSIONS: A broad spectrum of office-specific characteristics and
      personal considerations has to be considered when deciding whether to extend
      office hours. These factors are interdependent, and their importance varies among
      office personnel groups. The factors can be considered in a systematic fashion,
      however, providing a practice with useful, objective data on which to base its
      decision.

PMID- 10086763
TI  - Commitment to a regular physician: how long will patients wait to see their own
      physician for acute illness?
AB  - BACKGROUND: Continuity of care with a physician is associated with better health
      outcomes and greater patient satisfaction. Having a "regular doctor" could lead
      to greater continuity of care, but only if the patient consistently seeks care
      from this physician. How long will a patient wait for care if their usual
      physician is not available? Our study explored factors related to a patient's
      decision to seek care from another professional. METHODS: We analyzed the results
      of a statewide random digit dialing telephone survey of 658 Kentucky adults. Our
      study focused on the 466 adults who indicated they usually seek care from the
      same physician. Respondents were asked about seeing an alternate provider if they
      had an acute, non-life-threatening condition and their usual physician was not
      available. RESULTS: Of the respondents, 48.6% indicated they would seek care from
      another professional the same day, 41.6% would wait 1 day or more, and 9.8% would
      not see another professional. Patients with asthma were significantly more likely
      to wait for care from their regular physician (P <.05), as were patients who
      usually visited a physician's office instead of a clinic (P <.05). In a
      multivariate model, seeking alternate care the same day was significantly more
      likely among patients who were older, nonwhite, and who would seek alternate care
      at their usual site of care (P <.05). CONCLUSIONS: Maintaining continuity of care
      with their usual physician is important to patients. Patient and practice
      characteristics may influence the decision to wait for care in an effort to
      maintain continuity.

PMID- 10086764
TI  - Determining a minimum wrestling weight for interscholastic wrestlers.
AB  - BACKGROUND: Junior high school and high school boys participating in
      interscholastic wrestling are at risk when allowed to compete in a weight class
      that is too low, which can adversely affect their growth and general health. This
      study compared 3 different methods that physicians may use to determine the
      minimum wrestling weight of junior high and high school wrestlers. METHODS: At an
      unannounced school visit, the minimum wrestling weight of the wrestlers was
      calculated on the basis of 3 different methods of estimating the percentage of
      body fat: (1) Lange calipers; (2) the Ross Laboratories Adipometer calipers; and
      (3) bioimpedance analysis. RESULTS: Over a 2-year period, 104 boys interested in
      interscholastic wrestling participated in this comparison. Correlation among all
      3 methods was very high (consistently more than 98%). However, the 2 caliper
      methods agreed most closely with each other, with the Ross caliper overestimating
      minimum wrestling weight by an average of 0.6 kg. As compared with the Lange
      caliper method, bioimpedance underestimated minimum wrestling weight by an
      average of 2 kg. CONCLUSIONS: The agreement between the 2 caliper methods was
      sufficient to allow the simple, inexpensive caliper to be used instead of the
      more expensive Lange caliper. The bioimpedance method, which overestimated the
      percentage of body fat compared with the other methods, would allow too much
      weight loss. Using 3 quick skinfold measurements obtained with the inexpensive
      plastic Ross calipers and a chart of values, physicians can accurately calculate
      minimum wrestling weight for interscholastic wrestlers.

PMID- 10086765
TI  - Is acupuncture effective in the treatment of fibromyalgia?
AB  - BACKGROUND: We conducted this study to assess the effectiveness of acupuncture in
      the treatment of fibromyalgia syndrome (FMS), report any adverse effects, and
      generate hypotheses for future investigation. METHODS: We searched MEDLINE,
      EMBASE, Manual Therapy Information System, the Cochrane registry, the University
      of Maryland Complementary and Alternative Medicine in Pain, the Centralized
      Information Service for Complementary Medicine, and the National Institutes of
      Health Office of Alternative Medicine databases for the key words "acupuncture"
      and "fibromyalgia." Conference abstracts, citation lists, and letters
      supplemented the search. We selected all randomized or quasi-randomized
      controlled trials, or cohort studies of patients with FMS who were treated with
      acupuncture. Methodologic quality, sample characteristics, type of acupuncture
      treatment, and outcomes were extracted. Statistical pooling was not performed
      because of the differences in control groups. RESULTS: Seven studies (3
      randomized controlled trials and 4 cohort studies) were included; only one was of
      high methodologic quality. The high-quality study suggests that real acupuncture
      is more effective than sham acupuncture for relieving pain, increasing pain
      thresholds, improving global ratings, and reducing morning stiffness of FMS, but
      the duration of benefit following the acupuncture treatment series is not known.
      Some patients report no benefit, and a few report an exacerbation of FMS-related
      pain. Lower-quality studies were consistent with these findings. Booster doses of
      acupuncture to maintain benefit once regular treatments have stopped have been
      described anecdotally but not investigated in controlled trials. CONCLUSIONS: The
      limited amount of high-quality evidence suggests that real acupuncture is more
      effective than sham acupuncture for improving symptoms of patients with FMS.
      However, because this conclusion is based on a single high-quality study, further
      high-quality randomized trials are needed to provide more robust data on
      effectiveness.

PMID- 10086766
TI  - Feasibility of autologous blood donation in patients with placenta previa.
AB  - BACKGROUND: Debate continues as to whether autologous blood donation is feasible
      in patients with placenta previa. A recent study in a university setting
      concluded that routine autologous donation in patients with placenta previa is
      not indicated. In our study we assessed the feasibility of autologous blood
      donation for patients with placenta previa in a community-hospital setting.
      METHODS: We performed a chart review over a 5-year period of all patients
      admitted with placenta previa. A theoretical model was then applied to this data.
      To be eligible for autologous donation, the patient would need to be asymptomatic
      and have a hemoglobin level of 11 gm/dL or higher at 32 weeks' gestation.
      RESULTS: Fifty-nine patients were admitted with uncomplicated placenta previa,
      34% (20) of whom were eligible for autologous donation. We found that 20% (4) of
      patients who met eligibility criteria for autologous blood donation would have
      benefitted from predonation, and 10% (2) of patients meeting eligibility criteria
      might have become anemic at delivery because of the donation. CONCLUSIONS:
      Autologous donation is not feasible in most patients with placenta previa.
      However, the proportion of patients eligible for autologous blood donation in a
      community-hospital setting is 2.5 times the proportion of eligible donors in a
      university hospital setting (P = .003). Asymptomatic patients with placenta
      previa diagnosed by 32 weeks, who have a hemoglobin level of 11 gm/dL or above,
      may be safely offered this option.

PMID- 10086767
TI  - Posttraumatic stress disorder in primary care.
AB  - BACKGROUND: Primary care providers are aware of the importance of identifying
      depression and anxiety in their patients. The diagnosis of posttraumatic stress
      disorder (PTSD), however, is less of a priority. METHODS: Primary care physicians
      and nurse practitioners in an outpatient facility of a large health maintenance
      organization administered a psychiatric screening questionnaire to patients whom
      they suspected had depression or anxiety. Patients with positive results were
      referred for immediate consultation with a clinical psychologist. RESULTS: One
      hundred fourteen (38.6%) of the 296 patients referred for consultation met
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic
      criteria for PTSD. The most frequent traumas associated with PTSD were adult
      domestic violence and childhood abuse. Patients with a diagnosis of PTSD were
      frequent users of medical services in the 12 months before diagnosis. The
      majority of patients sought treatment in primary care settings, not mental health
      settings. CONCLUSIONS: Patients with PTSD often visit outpatient primary care
      settings. Medical providers may identify symptoms of depression or anxiety but
      may not recognize PTSD because of the high degree of overlap between these
      conditions, and the lack of familiarity with PTSD diagnostic criteria. We provide
      screening questions that may help physicians detect PTSD in their practices.

PMID- 10086768
TI  - Second order versus second rate.

PMID- 10086769
TI  - Serum chemistry tests.

PMID- 10086770
TI  - Walking in labor.

PMID- 10086771
TI  - Ugly stepchildren?

PMID- 10086772
TI  - Not an ideal study.

PMID- 10086773
TI  - Images in haematology. Diagnosis of angiotropic large B-cell lymphoma from a
      peripheral blood film.

PMID- 10086774
TI  - Prevention of vitamin K deficiency bleeding in newborns.
AB  - Newborn babies are born vitamin K deficient; however, the deficiency is not
      sufficiently severe to cause a vitamin K deficiency coagulopathy and haemorrhagic
      disease of the newborn (HDN). Severe vitamin K deficiency can develop quickly in
      breast-fed newborns and can result in the appearance of classic HDN during the
      first week of life or late HDN during the first 2 months of life. Both forms of
      the disease can be severe, causing brain damage and death. Classic and late HDN
      are prevented by the intramuscular administration of vitamin K at birth. Oral
      prophylaxis prevents classic HDN but is ineffective in preventing late HDN.
      Despite proven effectiveness of intramuscular vitamin K prophylaxis there have
      been concerns about the need for, and safety of, this therapy. This review
      provides evidence that there is need for intramuscular vitamin K prophylaxis for
      all babies in order to eradicate haemorrhagic disease of the newborn and
      concludes that there is no evidence that this therapy is harmful.

PMID- 10086775
TI  - Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in
      thrombocythaemia: a rationale for the use of low-dose aspirin as an
      antithrombotic agent.
AB  - The clinical course of patients with polycythaemia vera (PV) and essential
      thrombocythaemia (ET) is frequently complicated by arterial thrombotic events.
      The pathogenesis is not clearly understood but attributed to abnormalities in
      platelet function. An increase in platelet thromboxane formation has been
      described in the majority of asymptomatic patients with thrombocythaemia,
      probably reflecting spontaneous platelet activation in vivo. In the present study
      we prospectively investigated whether an increase in platelet thromboxane
      formation actually precedes arterial microvascular thrombosis. In addition, we
      studied the effect of selective inhibition of platelet thromboxane formation on
      clinical outcome by reinstitution of low-dose aspirin (50 mg/ d). Six ET patients
      and one PV patient participated in this study. Within 10 d after withdrawal of
      aspirin, three patients developed arterial microvascular thrombosis of
      extremities (erythromelalgia), which was preceded by a 3-30-fold increase in
      urinary thromboxane excretion as compared with patients who remained
      asymptomatic. The increased urinary thromboxane excretion and clinical signs
      could be inhibited by a platelet-specific aspirin regimen of 50 mg/d without
      affecting vascular cyclooxygenase, indicating that platelets were the main source
      of the increased thromboxane generation. These data suggest that in symptomatic
      patients an enhanced formation of thromboxane by platelets, reflecting platelet
      activation in vivo, precedes the development of arterial microvascular
      thrombosis. These data provide a rationale for using low-dose aspirin as an
      antithrombotic agent in thrombocythaemia.

PMID- 10086776
TI  - A prospective study of protein-specific assays used to investigate idiopathic
      thrombocytopenic purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a disorder in which platelets,
      sensitized by autoantibodies, are destroyed by the reticuloendothelial system.
      The diagnosis of ITP has been a clinical one because assays measuring platelet
      associated IgG (PAIgG) have low specificity. The recently introduced assays that
      measure antibodies against specific platelet glycoproteins (GP) offer the
      possibility of improved specificity. In this report we describe two prospective
      studies. In the first study we compared two protein-specific assays (AC and
      MAIPA) looking for the presence of autoantibodies against GP IIb/IIIa in 81
      patient samples. These results were compared with an immunoradiometric assay for
      PAIgG. The second study investigated the enhanced sensitivity of measuring anti
      GP Ib/IX autoantibodies in 76 patient samples. The protein-specific assays were
      able to differentiate immune from non-immune thrombocytopenia (specificity 91%,
      sensitivity 39%), whereas the PAIgG assay could not (specificity 19%, sensitivity
      78%). The addition of the Ib/IX AC assay maintained a specificity of 92% while
      increasing the diagnostic sensitivity to 66%. In contrast to the PAIgG assay,
      there was no correlation between the platelet count and the likelihood or degree
      of positivity within the control samples using the glycoprotein assays. These
      studies confirm that glycoprotein assays can be used as diagnostic tests for ITP.

PMID- 10086777
TI  - Protein disulphide isomerase mediates platelet aggregation and secretion.
AB  - Platelet surface thiols and disulphides play an important role in platelet
      responses. Agents that reduce disulphide bonds expose the fibrinogen receptor in
      platelets and activate the purified glycoprotein (GP) IIbIIIa receptor. Protein
      disulphide isomerase (PDI), an enzyme that rearranges disulphides bonds, is found
      on the platelet surface where it is catalytically active. We investigated the
      role of PDI in platelet responses using (1) rabbit anti-PDI IgG specific for PDI,
      (2) a competing substrate (scrambled ribonuclease A), and (3) the PDI inhibitor,
      bacitracin. Fab fragments of the rabbit anti-PDI IgG inhibited platelet responses
      to the agonists tested (ADP and collagen), whereas Fab fragments prepared
      identically from normal rabbit IgG had no inhibitory effect. Scrambled
      ribonuclease A blocked platelet aggregation and secretion, but native
      ribonuclease A did not. When biphasic platelet aggregation was examined using
      platelets in citrated plasma, the principle effect of bacitracin was on second
      phase or irreversible aggregation responses and the accompanying secretion. Using
      flow cytometry and an antibody specific for activated GPIIbIIIa (PAC-1), the
      rabbit anti-PDI Fab fragments substantially inhibited activation of GPIIbIIIa
      when added before, but not after, platelet activation. In summary, we have
      demonstrated that protein disulphide isomerase mediates platelet aggregation and
      secretion, and that it activates GPIIbIIIa, suggesting this receptor as the
      target of the enzyme.

PMID- 10086778
TI  - An international collaborative study on the INR calibration of freeze-dried
      reference plasmas.
AB  - A study was carried out to calibrate potential European Reference Plasmas for
      prothrombin time (PT) standardization. The International Normalized Ratio (INR)
      values of three freeze-dried candidate plasmas (one pooled normal and two pools
      from anticoagulated patients) were determined in 20 laboratories using six
      thromboplastin reagents comprising three International Reference Thromboplastins
      (human, rabbit and bovine), two recombinant human reagents and one placental
      human reagent. Interlaboratory variability of INR estimation was low with
      geometric coefficients of variation (gcv) <10% except in one case. Significant
      differences in mean INR were found between the different thromboplastins with
      lowest INR values found with the bovine reagent. INR values from the
      International rabbit and human reagents differed by <6% and were combined to give
      proposed assigned INR values. Significant differences in INR estimates from four
      thromboplastins of human origin may indicate that single assigned INR values are
      not applicable for use with all thromboplastin reagents. Field trials to assess
      the validity of single assigned INR values in clinical practice are required.

PMID- 10086779
TI  - Central venous catheter-associated thrombosis in severe haemophilia.
AB  - Significant subclavian vein thromboses associated with indwelling fully implanted
      (port-a-cath) devices are described in two boys with severe haemophilia A and
      factor VIII inhibitors. Investigations were prompted by prominent chest wall
      veins in one case, whereas the thrombosis was a chance finding in the other case
      during investigation of mechanical dislocation of the catheter tubing. Extensive
      collateral venous circulations were demonstrated by venography in both instances
      indicating that the thrombus had been present for some time. Possible
      contributing factors to the thromboses included desensitization therapy (both
      patients), high-dose FEIBA (in one patient) and use of lower doses of heparin for
      line flush than that recommended by some authors. Neither patient had a familial
      or non-familial predisposition to thrombosis.

PMID- 10086780
TI  - Successful treatment of a non-haemophilic patient with inhibitor to factor VIII
      by double-filtration plasmapheresis.
AB  - Factor VIII (FVIII) inhibitors appear in 3-20% of haemophilia A patients after
      injection of FVIII concentrates. However, autoantibodies to FVIII are also
      reported in non-haemophiliacs. In these patients FVIII inhibitor disappears
      spontaneously or diminishes in response to immunosuppressive therapy. However, a
      few patients show resistance to immunosuppressive therapy. We describe a non
      haemophilic elderly patient with acquired FVIII inhibitor who failed to respond
      to prednisolone. He was treated with double-filtration plasmapheresis (DFPP)
      which resulted in a very rapid reduction in inhibitor levels and resolution of
      symptoms.

PMID- 10086781
TI  - Haemostatic and fibrinolytic responses to bone marrow transplantation.
AB  - Thrombin and plasmin activation markers were serially measured in 80 patients
      undergoing bone marrow transplantation (BMT). There were prothrombotic and
      fibrinolytic responses observed during autograft and allograft BMTs. Thrombin
      antithrombin and prothrombin fragment F1+2 levels increased from day -7 to -3
      (P<0.0001) from 3.7 to 7 ng/ml and 1.2 to 1.63 nmol/l, respectively. A rise in
      plasmin-antiplasmin levels occurred between days 4 and 14 (P< 0.0004), from 393
      ng/ml on day -7 to a peak of 795 ng/ml on day 11. No correlation between reduced
      protein C levels post-BMT and a prothrombotic state was observed.

PMID- 10086782
TI  - Efficient inhibition of macrophage TNF-alpha production upon targeted delivery of
      K48R ubiquitin.
AB  - K48R ubiquitin (K48R-Ub) is an analogue of native ubiquitin that does not form
      polyubiquitin chain conjugates. Targeted delivery of this recombinant mutant
      ubiquitin to human macrophages results in an intracellular increase in the
      ubiquitin analogue. IkappaBalpha polyubiquitination and degradation were
      significantly inhibited in K48R-Ub targeted macrophages upon stimulation with
      lipopolysaccharide. The ability to reduce IkappaBalpha degradation was also
      associated with a reduced production of TNF-alpha, the gene of which is under NF
      kappaB control. At a concentration of 0.1 microM, dexamethasone was less
      effective than K48R-Ub in preventing IkappaBalpha depletion and TNF-alpha
      release. These data suggest that ubiquitin analogues are potent suppressors of
      TNF-alpha release in macrophages.

PMID- 10086783
TI  - Expression of vascular endothelial growth factor in sera and lymph nodes of the
      plasma cell type of Castleman's disease.
AB  - To evaluate the possible involvement of vascular endothelial growth factor (VEGF)
      in the pathogenesis of Castleman's disease, we studied VEGF levels in sera and
      supernatants of cultured lymph nodes from two patients with the plasma cell type
      of Castleman's disease, and analysed the expression of VEGF immunohistochemically
      in the lymph nodes. Clinically, one patient was classified as the localized type
      and the other as the multicentric type. Histologically, mature plasma cells and
      hyalinized vessels were prominent in the interfollicular region. The VEGF levels
      of the sera and the supernatants of cultured lymph nodes of both patients were
      higher than those of normal controls. VEGF was strongly expressed in plasma cells
      in the interfollicular region of the lymph nodes of both patients, but rarely in
      normal lymph nodes. Our results suggest that VEGF may be involved in the marked
      vascular proliferation in the interfollicular region of the lymph nodes of the
      plasma cell type of Castleman's disease.

PMID- 10086784
TI  - Persistent polyclonal B lymphocytosis with binucleated lymphocytes: a study of 25
      cases. Groupe Francais d'Hematologie Cellulaire.
AB  - Persistent and polyclonal lymphocytosis of B lymphocytes (PPBL) with binucleated
      lymphocytes is an entity characterized by a polyclonal lymphocytosis. The
      lymphocytosis is stable for years and binucleated lymphocytes are detected on
      peripheral blood smears. We previously described +i(3q) as a recurrent
      chromosomal abnormality in seven PPBL patients. In this study we report a large
      series of 25 PPBL patients and demonstrated that PPBL was associated with +i(3q)
      in 77% of cases, premature chromosome condensation (PCC) in 50% and both
      abnormalities in 41% of cases. Furthermore, we demonstrated that i(3q) was
      present in a minority of B cells, restricted to B lymphocytes independently of
      the kappa or lambda light Ig chain expression, and exclusively observed in non
      binucleated cells. The benign clinical course of PPBL and the lack of biological
      evolution in the majority of cases suggest that recognition of these disorders is
      so important that aggressive therapy in PPBL has to be avoided. Whether this
      syndrome represents a premalignant or benign disease remains unclear. The
      persistence of cytogenetic abnormalities after stopping tobacco use suggests no
      association with cigarette smoking.

PMID- 10086785
TI  - Transferrin receptor on peripheral blood lymphocytes in iron deficiency anaemia.
AB  - The effect of iron deficiency anaemia (IDA) on CD71 expression by peripheral
      blood lymphocytes was studied in 43 children with iron deficiency anaemia. 18
      healthy age-matched children were selected as the control group. 11 children with
      beta-thalassaemia trait were also studied. Lymphocytes bearing CD71 were
      enumerated by flow cytometric analysis of peripheral blood. At diagnosis, CD71+
      peripheral lymphocytes (mean+/-SE) was 5.90+/-0-76% in patients with IDA and
      12.60+/-0.98% in healthy controls (P=0.000). In beta-thalassaemia trait patients
      the peripheral blood CD71+ lymphocytes were 7.80+/-1.20%. In IDA patients there
      was a statistically significant correlation between the levels of CD71+
      peripheral lymphocytes and haemoglobin value (P = 0.000). In 19 patients studied
      at days 0 and 30 of oral iron therapy, the number of peripheral blood CD71+
      lymphocytes was shown to be increased from 5.90+/-0.76% to 12.11+/-1.21%. In
      severe IDA presence of a limited number of CD71+ peripheral blood lymphocytes
      indicated that severe IDA should be borne in mind when considering conditions
      responsible for the suppression of lymphocyte proliferation.

PMID- 10086786
TI  - Automated malaria detection by depolarization of laser light.
AB  - Anecdotal experience with full blood count (FBC) technology incorporating
      analysis of depolarized laser light (DLL) for the enumeration of eosinophils
      showed that malaria infection generated unusual distributions in the white cell
      channels. The objective of this study was to identify and define criteria for a
      diagnosis of malaria using this technology. To determine sensitivity,
      specificity, and positive and negative predictive values, 224 directed samples
      referred specifically for malaria were used; true positives were defined as those
      in which malaria was identified by microscopic and/or immunological methods. For
      the DLL method, positive was defined as one or more large mononuclear cell(s) for
      which the 90 degrees depolarized signal exceeded the 90 degrees polarized signal.
      To determine possible utility in a routine haematology laboratory setting, 220
      random undirected FBC samples were evaluated for possible malaria infection by
      the DLL method. Of the 224 directed samples, 95 were malaria positive as
      determined by microscopic and/or immunological methods, and 129 were negative.
      For the DLL method, overall sensitivity was 72% (90% in the case of Black
      Africans), and specificity 96%. Positive and negative predictive values overall
      were 93% and 82% respectively. In the utility study a single positive result was
      identified among the 220 samples studied. This was found to be from a patient
      with malaria. The detection of unexpected malaria by automated screening FBC
      analysis could substantially lower the mortality and morbidity from unascertained
      infection, especially in indigenous African peoples.

PMID- 10086787
TI  - Metabolic indicators of oxidative stress correlate with haemichrome attachment to
      membrane, band 3 aggregation and erythrophagocytosis in beta-thalassaemia
      intermedia.
AB  - Haematological data, genotype, transfusion requirements, metabolic indicators of
      oxidative stress (flux via hexose-monophosphate shunt (HMPS); steady state level
      of GSH and GSSG, NADPH and NADP; activity of anti-oxidant enzymes), parameters of
      membrane damage (aggregated band 3; membrane-bound haemichromes, autologous
      immunoglobulins (Igs) and C3 complement fragments) and erythrophagocytosis were
      measured in erythrocytes (RBC) of 15 beta-thalassaemia intermedia patients (nine
      splenectomized) with low, if any, transfusion requirements. Patients presented
      increased aggregated band 3, bound haemichromes, Igs and C3 complement fragments,
      and increased erythrophagocytosis. Bound haemichromes strongly correlated with
      aggregated band 3. Anti-band 3 Igs were predominantly associated with aggregated
      band 3. Erythrophagocytosis positively correlated with aggregated band 3,
      haemichromes and Igs, suggesting the involvement of haemichrome-induced band 3
      aggregation in phagocytic removal of beta-thalassaemic RBC. Splenectomized
      patients showed higher degrees of membrane damage and phagocytosis, significantly
      higher numbers of circulating RBC precursors, and tendentially higher numbers of
      reticulocytes. Basal flux via HMPS was increased twofold, but HMPS stimulation by
      methylene blue was decreased, as was the glucose flux via HMPS. GSH was
      remarkably decreased, whereas NADPH was increased. Except for unchanged catalase
      and glutathione reductase, anti-oxidant enzymes had increased activity. Negative
      correlation between HMPS stimulation by methylene blue and bound haemichromes
      indicated that the ability to enhance HMPS may counteract haemichrome
      precipitation and limit consequent membrane damage leading to
      erythrophagocytosis.

PMID- 10086788
TI  - A reverse dot-blot method for rapid detection of non-deletion alpha thalassaemia.
AB  - A reverse dot blot method based on membrane-bound allele-specific
      oligonucleotides as hybridization targets for amplified alpha-gene fragments has
      been developed for the rapid detection of four non-deletion alpha thalassaemia
      defects found in the Chinese. Since these non-deletion defects account for 22 8%
      of haemoglobin H disease, a sensitive, specific and rapid screening method should
      be of value.

PMID- 10086789
TI  - The potential of human mast cell progenitors to differentiate into mature mast
      cells remains after prolonged culture with flt3 ligand, interleukin-3 or
      granulocyte-macrophage colony stimulating factor.
AB  - Stem cell factor (SCF) plays a key role in the development of mast cells from
      haemopoietic progenitor cells. In this study we have investigated the effect of
      the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the
      SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By
      using delayed addition of SCF, we examined the potential of mast cell progenitors
      to keep their capacity to differentiate into mast cells after exposure to factors
      signalling differentiation into other lineages. Culture with either cytokine for
      3 weeks before transfer to SCF-containing medium resulted in the development of
      mast cells in all cultures. The appearance of mast cells was attenuated when the
      cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared
      to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells
      had not lost the capacity to develop into mast cells. In contrast, in cultures
      initiated with FL and transferred to medium containing SCF, the same amount of
      mast cells developed as in the SCF cultures. Thus, cells committed to the mast
      cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF
      and keep their potential to differentiate into mature mast cells.

PMID- 10086790
TI  - CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with
      aplastic anaemia.
AB  - Patients with aplastic anaemia (AA) frequently develop paroxysmal nocturnal
      haemoglobinuria (PNH) as a late complication. We investigated the frequency of
      the development of PNH features including a glycosyl phosphatidylinositol (GPI)
      anchoring defect in 73 Japanese patients with AA. A deficient expression of CD59
      was found on erythrocytes and/or granulocytes in 21/73 (28.8%) of the patients. A
      Ham/sugar water test was positive in 13/21 patients. We also examined mutations
      of the PIG-A gene in 11 patients with CD59 deficiency. A heteroduplex analysis
      detected PIG-A gene abnormality in 10/11 patients tested. Nucleotide sequencing
      was performed in six patients and identified eight mutations including three
      mutations in one patient. The mutations of the PIG-A gene were all different and
      included two single-base insertions, one single-base deletion, two two-base
      deletions, and one each of eight-base insertion and nine- and ten-base deletions.
      All mutations but one caused frameshifts. Our findings indicate that a high
      proportion of Japanese patients with severe AA have a GPI-anchoring defect and
      that the PIG-A gene is mutated in the AA patients who had a GPI deficiency. We
      found no significant difference in the pattern of the PIG-A gene mutation between
      the AA patients with a GPI deficiency and those with de novo PNH.

PMID- 10086791
TI  - A rapid single-laser flow cytometric method for discrimination of early apoptotic
      cells in a heterogenous cell population.
AB  - A recently reported cytometric method described the possibility of discriminating
      apoptotic from necrotic cells using FITC-labelled annexin V and propidium iodide
      (PI). Nevertheless, the brightness of PI-staining and its extensive spectral
      emission overlap with phycoerythrin (PE) does not permit the study of a subset of
      a heterogenous cell population with single laser instrumentation. The surface
      staining of a subset with PE in a heterogenous cell population therefore requires
      another exclusion dye to detect necrotic cells. We used 7-amino-actinomycin D (7
      AAD) that can be excited by the 488 nm argon laser line. 7-AAD emits in the far
      red range of the spectrum and 7-AAD spectral emission can be separated from the
      emissions of FITC and PE. The fluorescence parameters allow characterization of
      necrotic (7-AAD+ annexin V-FITC+ cells), apoptotic (7-AAD-annexin V-FITC+ cells)
      and viable cells (7-AAD- annexin V-FITC- cells) in a subset of PE+ cells. The
      value of this method was demonstrated by measuring apoptosis and necrosis in a
      model of HL-60 cells exposed to different inducers of cell death. The method was
      validated by fluorescent cell sorting in combination with morphologic examination
      of the sorted cells. The technique we present is particularly valuable in a
      clinical setting because it enables rapid multiparameter analysis of necrosis and
      early apoptosis in combination with cell surface phenotyping with a single laser.
      We present the effects of haemopoietic growth factor deprivation on myeloid
      progenitor CD34+ cells as an example of its application.

PMID- 10086792
TI  - Normal primitive haemopoietic progenitors are more frequent than their leukaemic
      counterpart in newly diagnosed patients with chronic myeloid leukaemia but
      rapidly decline with time.
AB  - We carried out studies to quantify Ph-negative progenitors both in steady state
      and during regeneration after chemotherapy and G-CSF in 23 newly diagnosed
      chronic myeloid leukaemia (CML) patients (group A) and in 14 individuals more
      than a year from diagnosis (nine in chronic and five in accelerated phase, group
      B). In steady-state bone marrow, Ph-negative long-term culture initiating cells
      (LTC-IC) and Ph-negative colony-forming-cells (CFC) were detected in 18/23 and
      14/23 patients of group A versus 3/14 and 3/14 patients of group B (P<0.001 and
      P<0.02, respectively). The absolute number of mobilized Ph-negative progenitors
      was markedly higher in group A versus group B (P<0.02 for LTC-IC, P<0.003 for
      CFC). 12/16 newly diagnosed patients mobilized Ph-negative LTC-IC only and the
      yield was in the range of normal allogeneic donors. Overall the frequency of Ph
      negative LTC-IC in the bone marrow predicted the yield of Ph-negative LTC-IC
      mobilized into peripheral blood (P<0.001). The bone marrow frequency of Ph
      positive LTC-IC was considerably lower than the normal counterpart. Taken
      together, these findings suggest that normal progenitors are relatively well
      preserved in newly diagnosed CML patients, but tend to rapidly decline with time.
      This observation helps in the understanding of the pathogenesis of CML and has
      potential implications for autografting. The optimal time for a successful
      collection of Ph-negative circulating progenitors would appear to be soon after
      diagnosis.

PMID- 10086793
TI  - Linear reduction of clonal cells in stem cell enriched grafts in transplanted
      multiple myeloma.
AB  - In 30 patients with multiple myeloma who were scheduled for peripheral blood stem
      cell transplantation, a quantitative analysis of the stem cells following
      enrichment by anti-CD34 was carried out. To detect the cells of the specific
      myeloma clone, polymerase chain reaction (PCR) was performed using unique allele
      specific oligo primers for the immunoglobulin heavy chain rearrangement. The
      clonogenic cells before and after stem-cell enrichment, were quantified by a
      limiting dilution assay and a highly sensitive semi-nested PCR combined with a
      real-time quantitative PCR. In order to accomplish a statistically adequate end
      point analysis, a large number of PCR analyses (40 per sample) were performed. By
      this technique the lowest detection limit observed was one myeloma cell per 106
      cells. Myeloma cells were detected in 29/30 samples from the CD34-enriched
      fraction. The CD34 selection procedure resulted in a median 28-fold enrichment of
      CD34+ haemopoietic precursor cells. The stem-cell selection reduced the median
      concentration of clonal cells per million total cells by half, with a highly
      significant linear relationship between the number of myeloma cells before and
      after stem cell enrichment. The median depletion of clonal cells by the overall
      procedure was 2.15 log units, corresponding to a reduction of the total quantity
      of clonal cells reinfused into the patients by at least 99.3%. We conclude that
      CD34+ cell enrichment led to a reliable tumour cell depletion of the order of 2
      log, which may not be sufficient since the total number of tumour cells in the
      leukapheresis product was 7.2 log (median).

PMID- 10086794
TI  - Intermediate-dose intravenous melphalan and blood stem cells mobilized with
      sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis.
AB  - AL amyloidosis patients ineligible for dose-intensive melphalan (200 mg/m2) were
      enrolled on a phase 11 trial to be treated with two cycles of intermediate-dose
      melphalan (IDM 100 mg/m2) and mobilized blood stem cells (BSC). For mobilization
      patients were randomized to either GM-CSF 250 microg/m2 for 3 d followed by G-CSF
      10 microg/ kg for 3 d (GM+G), or G-CSF 10 microg/kg for 6 d (G-alone), with
      leukaphereses on days 5, 6 and 7. To minimize morbidity, we planned to support
      each cycle with 3 5 x 106 CD34+ cells/kg and had a collection target of 7 x 10(6)
      CD34+ cells/kg. Those who did not achieve the target were treated with one cycle
      of IDM. 30 patients, a median of 62 years old and 7 months from diagnosis, were
      enrolled. Both mobilization regimens were generally well tolerated, and similar
      in terms of CD34+ cells and CFU-GM collected, but only 6/28 patients achieved the
      collection target (GM+G four, G-alone two). Despite a 19% incidence of grade 4
      toxicities, IDM therapy was well tolerated. At a median follow-up of 24 months
      (19-36) 57% of patients had survived, 17% with durable complete haematological
      responses and 40% with improved or stable amyloid organ involvement, including
      3/9 patients with predominant cardiac amyloid who are alive 2-3 years after
      treatment. The 100 d mortality was 20%. In conclusion, no definitive differences
      were identified between the mobilization regimens and IDM was an active regimen
      in AL for selected patients.

PMID- 10086795
TI  - Infections in adults undergoing unrelated donor bone marrow transplantation.
AB  - This study retrospectively reviews infections over a 7-year period in 60
      consecutive adults (median age 25 years) undergoing their first unrelated donor
      bone marrow transplant (UD-BMT). T-cell depletion was employed in 93%. More than
      half the patients had one or more severe, potentially life-threatening,
      infections. There was a high incidence of invasive fungal infections (Aspergillus
      17, Candida four), despite the use of itraconazole or amphotericin prophylaxis.
      Ten Aspergillus infections occurred beyond 100 d. Two patients (11%) with
      invasive aspergillosis survived. Clustering of infections was noted, with
      invasive fungal infections significantly associated with bacteraemias (OR 3.73,
      P=0.06) and multiple viral infections (OR 4.25, P=0.05). There were 21 severe
      viral infections in 16 patients, with CMV disease occurring in four patients
      only; viral pneumonitis was predominantly due to 'community respiratory' viruses.
      Most early bacteraemias (68%) were due to Gram-positive organisms. The majority
      of episodes of Gram-negative sepsis were caused by non-fastidious non
      fermentative bacteria, such as Pseudomonas spp. and Acinetobacter spp.,
      historically regarded as organisms of low pathogenicity. In patients with
      successful engraftment and minimal graft-versus-host disease, late infections
      suggestive of continued immune dysfunction (shingles, recurrent lower respiratory
      infections, Salmonella enteritis and extensive warts) were common.

PMID- 10086796
TI  - Treatment of advanced myelodysplastic syndrome with a regimen including
      recombinant human granulocyte colony-stimulating factor preceding allogeneic bone
      marrow transplantation.
AB  - We treated 13 patients with morphologically advanced myelodysplastic syndrome
      using cytosine arabinoside and total body irradiation, followed by allogeneic
      marrow transplantation from HLA-identical sibling donors. Granulocyte colony
      stimulating factor (G-CSF) was added to the preparative regimen to selectively
      increase chemosensitivity of leukaemic cells and to improve transplant outcome.
      No regimen-related deaths occurred, and no side-effects related to the addition
      of G-CSF were observed except for transient mild bone pain. At a median follow-up
      time of 39 months the projected 5-year disease-free survival and 5-year overall
      survival were 67.7% and 75.5%, respectively, with only one case showing
      cytogenetic relapse. The preparative regimen including G-CSF is feasible, and
      preliminary results seem to be encouraging. However, a larger trial is clearly
      warranted to evaluate its efficacy.

PMID- 10086797
TI  - Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia:
      contribution to differential diagnosis.
AB  - To ascertain the value of magnetic resonance (MR) imaging in the differential
      diagnosis between myelofibrosis (MF) and essential thrombocythaemia (ET), 38
      patients were analysed. 20 patients had MF (idiopathic myelofibrosis, 15 cases;
      post-ET myelofibrosis, four cases; post-polycythaemic MF, one case) and 18 ET.
      Mean age was 61.5 years (range 30-89) for patients with MF and 60.9 years (range
      26-83) for ET patients. MR imaging was performed in the dorsal vertebrae in all
      cases, and also in both femurs in 2 5 of the patients. In most ET cases the MR
      signal of the dorsal vertebrae was not modified, whereas it was markedly reduced
      in MF (P=0.0000001). With regard to femoral marrow, it was usually fatty in ET,
      with an absent to moderate degree of reconversion seen in the 14 cases analysed,
      contrasting with the marked degree of reconversion noted in 10/11 patients with
      MF (P=0.000007). An inverse correlation was demonstrated between the vertebral
      signal and the degree of femoral reconversion. These differences were due to the
      fact that in ET the bone marrow adipose tissue is grossly preserved, whereas in
      MF it is usually markedly decreased or absent. The above results indicate that MR
      imaging is a useful tool for the differential diagnosis of ET and MF, with the
      usefulness of this technique increasing when vertebral and femoral bone marrow
      studies are combined.

PMID- 10086798
TI  - Chlorambucil resistance in B-cell chronic lymphocytic leukaemia is mediated
      through failed Bax induction and selection of high Bcl-2-expressing subclones.
AB  - Our previous data have shown that high Bct-2/ Bax ratios in chronic lymphocytic
      leukaemia (B-CLL) correlate with in vitro apoptosis and clinical resistance. We
      have now monitored the in vitro viability of B-CLL cells in relation to Bcl-2 and
      Bax expression over a 48 h time course following exposure to chlorambucil. The
      results showed that Bax up-regulation was essential for chlorambucil-induced
      apoptosis in B-CLL cells and a 3-fold increase in expression within 4 h of
      exposure to drug was typically observed in sensitive cells; resistant cells
      failed to up-regulate Bax at all. In contrast, the constitutively high levels of
      Bcl-2 found in B-CLL cells were found to be down-regulated in apoptotic cells but
      the mean Bcl-2 expression in viable cells was increased, probably as a result of
      the loss of lower Bcl-2-expressing cells into the apoptotic compartment. Taken
      together, these data add further weight to the suggestion that Bcl-2/Bax ratios
      may be pivotal in determining the fate of B-CLL cells. Furthermore, the Bcl-2/Bax
      ratios found in apoptotic B lymphocytes were remarkably similar in the treated,
      untreated and normal control cells, which suggests that there is a universal Bcl
      2/Bax ratio threshold for cell survival and cell death.

PMID- 10086799
TI  - IL4 production and increased CD30 expression by a unique CD8+ T-cell subset in B
      cell chronic lymphocytic leukaemia.
AB  - Phenotypic and functional abnormalities within the residual non-B-cell
      compartment of B-cell chronic lymphocytic leukaemia (CLL) suggest an interaction
      between tumour cells and host immune effectors. To explore the possibility of a
      polarized Th1/Th2 response we have studied CD30 antigen expression and the
      pattern of cytokine production by purified CLL T cells. Activated T cells from
      CLL patients showed a significant increase in the expression of CD30 compared to
      normal controls. Accordingly, high levels of soluble CD30 were detected in
      supernatants from activated T-cell cultures, as well as in CLL serum samples.
      Messenger RNA for IL4 was found in both resting and, to a greater extent, in
      activated CLL T lymphocytes. The latter cells were also capable of releasing IL4.
      Three-colour immunofluorescence analyses revealed a strong CD30 expression in the
      CD3+/CD8+/CD28- large granular lymphocyte subset, which is considerably expanded
      in CLL. Production of IL4, as well as expression and release of CD30 by these T
      cells, was conclusively demonstrated at the clonal level. These findings document
      an expansion of a peculiar subset of 'Th2-like' cells in CLL, with an increased
      IL4 production and CD30 expression and release, that are likely to contribute to
      both the B-cell accumulation and immune-defects characteristic of this disease.

PMID- 10086800
TI  - The incidence of trisomy 3 in splenic lymphoma with villous lymphocytes: a study
      by FISH.
AB  - Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade B-cell
      lymphoproliferative disorder characterized by splenomegaly and circulating
      villous lymphocytes. The relationship between SLVL and splenic marginal zone
      lymphoma (SMZL), a disorder with identical splenic histology to SLVL, is not
      clear. Previous studies have failed to show a consistent karyotypic abnormality
      in SLVL whereas trisomy 3 has been reported in patients with SMZL. The presence
      of trisomy 3 in SMZL and its absence in SLVL has been viewed as evidence that
      these are different diseases. However, it is possible that the frequency of
      trisomy 3 in SLVL has been underestimated because previous studies have relied on
      conventional cytogenetics. We have therefore used interphase fluorescence in situ
      hybridization (FISH) to re-assess the frequency of trisomy 3 in SLVL. We studied
      70 patients, who were stratified into four groups according to the percentage of
      circulating villous lymphocytes. Trisomy 3 was found overall in 17% of patients.
      In particular, trisomy 3 was detected in 13% of cases with >50% of villous
      lymphocytes and which were considered typical of SLVL. In conclusion, we have
      demonstrated that some patients with SLVL have circulating cells with trisomy 3,
      which does not support the view that SLVL and SMZL are different diseases on the
      basis of the incidence of trisomy 3.

PMID- 10086801
TI  - Development of an EORTC questionnaire module to be used in health-related quality
      of-life assessment for patients with multiple myeloma. European Organization for
      Research and Treatment of Cancer Study Group on Quality of Life.
AB  - A multiple myeloma-specific quality-of-life questionnaire module has been
      designed in collaboration with the EORTC Quality-of-Life Study Group to be used
      in clinical trials with the EORTC QLQ-C30, a general cancer questionnaire. Strict
      methodology was employed to ensure thorough and appropriate development of the
      module. An extensive literature review was performed to identify health-related
      quality-of-life issues relevant to patients with multiple myeloma. Semi
      structured interviews were then carried out in several European countries with
      health-care providers experienced in the treatment of patients with multiple
      myeloma, and with a group of patients with multiple myeloma, to identify the
      issues which were most important to patients. A questionnaire was devised from
      the list of issues, using a 1-week time-frame and response categories consistent
      with the EORTC QLQ-C30. The provisional questionnaire and the EORTC QLQ-C30 were
      administered to patients with multiple myeloma in each participating country with
      further semi-structured interviews to refine the content and design of the
      questionnaire. A review of the results obtained in each stage of development
      resulted in a 24-item myeloma-specific module, the EORTC QLQ-MY24, which assesses
      disease-specific symptoms and their impact on everyday life, treatment side
      effects, social support, and future perspective. The module is currently
      undergoing further international field-testing to assess its psychometric
      properties.

PMID- 10086802
TI  - Combination therapy with fludarabine and cyclophosphamide as salvage treatment in
      lymphoproliferative disorders.
AB  - Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's
      lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven
      patients) were treated with a combination of fludarabine 25 mg/m2/d and
      cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had
      previously received purine analogue therapy of which four had progressive disease
      during treatment. The overall response rate of patients with CLL was 71% (28% CR,
      43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and
      vomiting which was maximal in the 3 d after therapy, infections and
      haematological suppression which was prolonged in some patients. This
      combination, which is based on a rational prediction of synergistic activity, is
      highly effective but associated with significant problems with tolerance.

PMID- 10086803
TI  - Expression of PRAD1/cyclin D1 in plasma cell malignancy: incidence and prognostic
      aspects.
AB  - We analysed PRAD1/cyclin D1 expression in 20 patients with plasma cell malignancy
      by Northern analysis. 6/17 multiple myeloma patients and 3/3 plasma cell
      leukaemia patients showed PRAD1/cyclin D1 expression. This incidence appeared to
      be higher than the expected incidence based on previous studies. Southern
      analysis did not show rearrangement of the bcl-1 region. Although there was no
      statistical difference, the PRAD1/cyclin D1 negative group showed a 1-year
      survival of 81.8%, 3-year survival of 45.5% and 5-year survival of 22.7%, and
      those for the PRAD1/cyclin D1 positive group were 63.5%, 16.9% and 16.9%,
      respectively. Further study is required to determine whether PRAD1/cyclin D1
      expression is a prognostic factor.

PMID- 10086804
TI  - Identification of the inverted chromosome 16 using chromosome painting.
AB  - The inverted chromosome 16 is commonly associated with acute myelomonocytic
      leukaemia (AML) M4 with bone marrow eosinophilia. Cytogenetic identification of
      the inverted chromosome 16 can be difficult. To help identify the inversion in
      bone marrow samples from patients referred for the diagnosis of AML-M4, we
      applied the molecular cytogenetic technique of chromosome painting using
      chromosome 16 p-arm paint. The results were concordant with standard chromosome
      analyses and clearly allowed for the identification of a pericentric inversion
      within chromosome 16 even in poor-quality metaphase spreads.

PMID- 10086805
TI  - Detection of weak D and D(VI) red cells in D-negative mixtures by flow cytometry:
      implications for feto-maternal haemorrhage quantification and D typing policies
      for newborns.
AB  - Quantitation of feto-maternal haemorrhage (FMH) by flow cytometry (FC) has been
      shown to be more accurate than the Kleihauer-Bekte test. Fetal cells will be
      predominately of R1r or R2r phenotype, with antigen site numbers per cell (SPC)
      of between 9900 and 16000. If the fetus is of weak D or partial D(VI) phenotype,
      fewer SPC will be present. Red cells from 20 adult weak D samples were mixed with
      rr red cells to give 1% mixes. Mixtures were stained and analysed by FC, using
      two different monoclonal reagents. The SPC of each sample was measured using SOL
      ELSA with Scatchard plot analysis. 18 samples could not be distinguished and had
      <1000 SPC. Two samples that could be distinguished had 1350 and 3000 SPC. Red
      cells from seven samples of D(VI) were also analysed. None of these samples could
      be distinguished: SPC were all <1000. Although one of the reagents used reacts
      with D(VI) cells, quantitation of a D(VI) FMH would not be possible due to low
      SPC. The ability of fetal red cells with low Rh D SPC to cause immunization is
      questionable; failure to measure FMH in these cases is unlikely to cause clinical
      problems, as long as suitably sensitive serological reagents and techniques are
      used to type all weak D and D variant babies as Rh D positive, and thus ensure
      that the mother is given the appropriate dose of anti-D.

PMID- 10086806
TI  - Prevalence and persistence of a novel DNA TT virus (TTV) infection in Japanese
      haemophiliacs.
AB  - To clarify the clinical implication of a newly discovered 'TT virus (TTV)', we
      assayed TTV DNA in sera from 50 haemophiliacs by a seminested-PCR. TTV DNA was
      detected in 75% (35/50), which was a much higher prevalence than for HBV (HBc
      Ab), HCV RNA, or HGV RNA. In particular, TTV DNA was found in 44.4% (4/8) of
      patients who had been treated only with virally inactivated factor VIII
      concentrates. Elevated ALT levels were observed in patients with HCV RNA and TTV
      DNA; however, the elevation in TTV DNA was obtained from patients co-infected
      with HCV RNA (62.9%, 22/35). There was no significant difference in ALT levels
      between TTV DNA-positive and DNA-negative in patients without HCV RNA. 85.3%
      (35/41) of TTV DNA-positive sera in 1990 were again positive for TTV DNA in 1995.
      These findings suggest that many haemophiliacs have been infected with TTV.
      Although TTV infection was not associated with serum ALT elevation, persistent
      TTV infection may contribute to cryptogenic hepatic failure in haemophiliacs.

PMID- 10086807
TI  - Definition of a standard-risk group in children with AML.
AB  - To define paediatric AML patients with a favourable outcome in order to design a
      risk-adapted therapy, we analysed 489 children under 17 years of age treated
      similarly in studies AML-BFM 83 and 87. 369 patients (75.4%) achieved remission.
      Estimated probabilities of survival, event-free survival (EFS) and disease-free
      survival (DFS) at 5 years were 50% (SE 2%), 43% (SE 2%) and 58% (SE 3%),
      respectively. Multivariate analysis revealed bone marrow blasts on day 15,
      morphologically defined risk groups and hyperleucocytosis to be of prognostic
      value. EFS at 5 years estimated for patients with < or = 5% and >5% blasts on day
      15 were 56% (SE 3%) v 27% (SE 4%); for the favourable morphological subgroups
      (M1/M2 with Auer rods, M3 and M4eo) it was 60% (SE 4%) compared with other
      patients (33%, SE 3%), P (Kaplan-Meier) = 0.0001 each. Hyperleucocytosis proved
      to be an independent prognostic factor, indicating a high risk, especially for
      early failure. The specific karyotypes t(8;21), t(15;17) and inv16 were closely
      related to the favourable morphology and outcome was in the same range. We
      conclude that for the definition of a standard-risk group a combination of
      morphological and response criteria may be sufficient. The standard-risk group
      defined by favourable morphology and a blast cell reduction on day 15 (not
      required for M3) comprises 31% of all patients, P survival, pEFS and pDFS at 5
      years were 73% (SE 4%), 68% (SE 5%) and 76% (SE 4%), respectively.

PMID- 10086808
TI  - Update statement from the conference 'Autologous transfusion', 3 years on--what
      is new? what has happened?" held at the Royal College of Physicians of Edinburgh,
      10-11 November 1998.

PMID- 10086809
TI  - Adult refractory chronic idiopathic thrombocytopenic purpura: can dapsone be
      proposed as second-line therapy?

PMID- 10086810
TI  - False positive reactions for CD7 of blast cells in patients with acute
      myelogenous leukaemia.

PMID- 10086811
TI  - CD34+CD38-HLA-DR- correlate more closely than CD34+CD38- with engraftment post
      PBSC transplantation.

PMID- 10086812
TI  - Cerebellar toxicity following hyperCVAD regimen for acute lymphoblastic
      leukaemia.

PMID- 10086813
TI  - Learning from case reports: diagnostic issues in an epidemiologic study of
      pancreatic cancer.
AB  - Epidemiologic studies on exocrine pancreatic cancer show a large heterogeneity in
      diagnostic criteria applied to define "caseness." Reanalyses conducted after
      review of diagnostic information have yielded substantially different results
      than those based on more crude classifications of disease. During a multicenter
      prospective study on mutations in the K-ras gene in pancreatic and biliary
      diseases, hospital diagnoses from 602 patients were reviewed by a panel of
      experts. There were two main motivations to do so: a generic interest for the
      quality of the diagnostic data, and the anticipation that a firm diagnosis could
      be needed to assess whether patients whose tumors did not harbor the mutation
      were true negatives or false negatives. In addition, the review of diagnoses was
      helpful to minimize tissue misclassification, and it had a high educational value
      for clinicians and epidemiologists. This article illustrates why and how this was
      so through a brief presentation of the 10 most significant cases. With respect to
      selection and classification of subjects, the main issues that studies on
      pancreatic cancer need to address are the differential diagnosis of exocrine
      pancreatic cancer and pancreatitis, the differential diagnosis of exocrine
      pancreatic cancer and other abdominal tumors, and the use of survival as a
      hallmark of pancreatic cancer. In epidemiologic studies of pancreatic cancer, it
      is warranted that a panel of experts centrally reviews all the existing
      diagnostic evidence (cytohistological and other) of all patients, regardless of
      whether they have cytohistological confirmation and of their hospital discharge
      diagnosis.

PMID- 10086814
TI  - Statistical methods in epidemiology: a comparison of statistical methods to
      analyze dose-response and trend analysis in epidemiologic studies.
AB  - Evaluation of various statistical methods to describe accurately associations
      between exposures and disease are constantly being explored. Spline regression
      has been suggested as an alternative to using categorized variables in studies of
      disease etiology, as it uses all data points to estimate the shape of the
      association between a given exposure and disease outcome. It has been proposed
      that this method is especially beneficial when associations are concentrated in a
      small range of the overall distribution of the exposure. In this study, we use
      data from a large case-control study of colon cancer to evaluate associations
      obtained from logistic regression models that use spline regression for main
      exposure and confounder effects with those that use categorized variables for
      main exposure. Our results show that for variables for which the association
      appears to be linear, such as body size and dietary intake of calcium, fiber, and
      cholesterol, associations are similar when estimates are generated from spline or
      categorized variable models. For other variables, such as total energy intake,
      for which associations appear to be strongest in the upper end of the
      distribution, estimates of association appear to be conservative when using
      categorized variables. The data also suggest that selection of cut points for the
      categorized variables may have an impact on the associations observed. Spline
      regression appears to be useful to estimate the shape of the association between
      a given exposure and disease and may provide guidance as to the appropriateness
      of using categorized variables. The risk estimates from spline regression appear
      to be similar to those from traditional categorical methods. When effects are
      large or rapidly changing, spline models may more appropriately describe the
      association.

PMID- 10086815
TI  - The Delphi list: a criteria list for quality assessment of randomized clinical
      trials for conducting systematic reviews developed by Delphi consensus.
AB  - Most systematic reviews rely substantially on the assessment of the
      methodological quality of the individual trials. The aim of this study was to
      obtain consensus among experts about a set of generic core items for quality
      assessment of randomized clinical trials (RCTs). The invited participants were
      experts in the field of quality assessment of RCTs. The initial item pool
      contained all items from existing criteria lists. Subsequently, we reduced the
      number of items by using the Delphi consensus technique. Each Delphi round
      comprised a questionnaire, an analysis, and a feedback report. The feedback
      report included staff team decisions made on the basis of the analysis and their
      justification. A total of 33 international experts agreed to participate, of whom
      21 completed all questionnaires. The initial item pool of 206 items was reduced
      to 9 items in three Delphi rounds. The final criteria list (the Delphi list) was
      satisfactory to all participants. It is a starting point on the way to a minimum
      reference standard for RCTs on many different research topics. This list is not
      intended to replace, but rather to be used alongside, existing criteria lists.

PMID- 10086816
TI  - Self-reported and performance-based functional status and associated factors
      among elderly men: the Finnish cohorts of the Seven Countries Study.
AB  - Health and functional status were studied in 470 men aged 70-89, the survivors of
      the Finnish cohorts of the Seven Countries Study. We aimed to compare subjective
      (self-reported activity of daily living [ADL]) and objective methods (four
      physical performance tests) in the assessment of physical function and to
      identify which factors are related to physical function. Poor ADL and decreased
      physical performance were mainly explained by the same health-related factors.
      The strongest determinants of ADL were depressive symptomatology odds ratio [OR]
      4.8, 95% confidence interval [CI] 2.7-8.8), osteoarthritis (OR 3.3, 95% CI 1.8
      5.9), vertigo (OR 2.5, 95% CI 1.2-5.5) and diabetes (OR 2.3, 95% CI 1.2-4.6).
      Self-reported ADL and performance-based measures were in general strongly
      correlated with each other, although there was some discordance owing to the fact
      that these performance tests examine functional limitations, whereas the self
      reported ADL reflects disability. The choice of which measurement to use in
      assessing functional status should be based on research objectives and the type
      of population under study.

PMID- 10086817
TI  - Impact of joint impairment on disability-specific domains at four years.
AB  - The objective of this study was to assess the longitudinal impact of joint
      impairment on overall disability and crossing domain-specific thresholds for
      physical activity, mobility, dexterity, instrumental activities of daily living
      (IADL), and activities of daily living (ADL) that are associated with use of long
      term care. This 4-year longitudinal study observed 484 persons older than age 60.
      Logistic regression assessed the contribution of demographics, psychological
      mediators, lower- and upper-extremity joint impairment, and comorbidities to
      increased domain-specific self-reported disability above a threshold associated
      with use of long-term care. Lower-extremity joint impairment and age predicted
      crossing thresholds by year 4 in physical activity, mobility, IADL, and ADL
      disability that were associated with use of long-term care. Lower-extremity joint
      impairment is a strong risk factor for future disability that is associated with
      use of long-term care.

PMID- 10086818
TI  - Ankle-arm index as an indicator of atherosclerosis: its application as a
      screening method.
AB  - The ankle-arm blood pressure index (AAI) is seldom used to screen for
      atherosclerotic diseases other than lower extremity arterial disease. This study
      was conducted to investigate whether the AAI can be used as a screening test for
      atherosclerotic diseases in general. The subjects were 446 male workers in a
      copper smelter. Fundoscopic examinations, electrocardiograms, serum cholesterol
      and triglyceride measurements, and AAI measurements were conducted. Information
      on past medical histories of diabetes mellitus and ischemic heart disease,
      smoking, alcohol intake, duration of sleep and physical activity were collected.
      The AAI correlated well with the results of the fundoscopic examinations, and an
      AAI of 1.00 gave the maximum sensitivity specificity product. The same AAI value
      also gave the maximum products for ST segment depression in electrocardiograms
      and the past history of ischemic heart disease. Multiple logistic regression
      analysis showed that a low AAI value was related to higher systolic blood
      pressure and current smoking but was inversely related to alcohol intake. Our
      study validated the AAI in predicting persons with risk factors of
      atherosclerotic diseases. The AAI measurements can be conducted at low cost,
      using simple techniques, and are noninvasive. We propose that the AAI be widely
      used to screen for atherosclerotic diseases.

PMID- 10086819
TI  - Prospective study of factors influencing the onset of natural menopause.
AB  - Late or early menopause has been implicated in risk of several chronic diseases
      in women. To study factors influencing the onset of natural menopause, the
      authors analyzed the follow-up data of 4694 premenopausal women who enrolled in
      the New York University Women Study at ages 34-61. In an average of 5.4 years of
      observation, there were 2035 incidences of menopause, with the median age of 51.3
      years. Current smokers experienced menopause 0.75 years earlier than never
      smokers. Those who smoked more than 10 cigarettes per day had a 40% increase in
      risk of earlier menopause. In contrast, women who had three or more children
      experienced menopause 0.86 years later than nulliparous women, and Jewish women,
      0.66 years later than Catholic women. There was also a modest increase in the age
      at menopause with increasing body mass index. This prospective study provides
      solid epidemiologic evidence that several factors other than cigarette smoking
      have impact on the onset of natural menopause.

PMID- 10086820
TI  - Postmenopausal estrogen use and invasive versus in situ breast cancer risk.
AB  - To examine the effect of cancer histopathology on the relationship between
      estrogen-replacement therapy (ERT) use and breast cancer risk, we performed a
      case-control study of 109 postmenopausal women 45 years or older with in situ or
      invasive breast cancer matched to 545 controls. When in situ and invasive tumors
      were combined, the overall odds ratio (OR) describing the association between ERT
      use and breast cancer risk was not statistically significantly elevated (adjusted
      OR = 1.48, 95% confidence interval [CI] = 0.89-2.47). When the analyses were
      confined to women with invasive disease, risk estimates were uniformly higher
      (adjusted OR = 1.85, 95% CI = 1.00-3.45). In contrast, the overall estimate for
      the relationship between ERT use and in situ breast cancer was close to 1
      (adjusted OR = 1.08, 95% CI = 0.42-2.77). The positive association between ERT
      use and invasive breast cancer we observed, and the lack of association in women
      with in situ disease, may represent a distinct biological difference or may be
      related to the small sample size of our study.

PMID- 10086821
TI  - Postmastectomy/postlumpectomy pain in breast cancer survivors.
AB  - Few studies have focused on careful assessment of postmastectomy pain (PMP); a
      chronic neuropathic pain syndrome that can affect women postlumpectomy or
      postmastectomy for breast cancer (BC). Study aims were to determine the
      prevalence of PMP in an outpatient sample of breast cancer survivors (BCS),
      describe subjective and objective characteristics of PMP, and examine the
      relationship between PMP and quality of life. Breast cancer survivors (n = 134)
      participated in telephone interviews, and those reporting PMP (n = 36) were
      invited to a pain center for further evaluation and treatment. Results show PMP
      is a distinct, chronic, pain syndrome affecting 27% of BCS. Findings support the
      need for clinical trials evaluating the effectiveness of nonpharmacological or
      cognitive behavioral therapies in alleviating mild to moderate PMP.

PMID- 10086822
TI  - Evaluation of diagnostic imaging tests: diagnostic probability estimation.
AB  - In the evaluation of a diagnostic imaging test for the diagnosis of a particular
      illness in a particular category of patients, the test should be construed as
      leading to a test result in the sense of a set of descriptive readings from the
      image(s), not interpretation of these; and in the evaluation of the test,
      therefore, the first challenge is the translation of each test result (set of
      readings) into the corresponding probability that the illness is present. This
      interpretive translation should not be subjective, nor should it be based on an
      objective algorithm founded on clinical judgments. Instead, a suitable diagnostic
      probability function (of the elements in the test result) should be derived
      empirically by logistic regression analysis of suitable data. We illustrate this
      alternative outlook by reanalysis of the data from the Prospective Investigation
      of Pulmonary Embolism Diagnosis.

PMID- 10086823
TI  - Bias in the assessment of family history of melanoma and its association with
      dysplastic nevi in a case-control study.
AB  - Family history of melanoma is an important risk factor for both melanoma and, it
      is thought, dysplastic nevi. However, assessment of family history of melanoma in
      epidemiologic investigations has typically been limited to interview of the
      proband. As part of a case-control study of dysplastic nevi, we attempted to
      confirm family histories. We disproved about half of the reported family
      histories of melanoma among first-degree relatives, and confirmed them by medical
      records in only 17%. Few family histories pertaining to other relatives could be
      confirmed. We documented the association of melanoma family history with
      dysplastic nevus risk, and we further documented a substantially greater odds
      ratio for this association when history was based on confirmation by medical
      records, compared to confirmation by proband interview only. The bias thus
      documented must be considered in evaluating the many published epidemiologic
      studies of melanoma and related disorders. Future research should attempt to
      confirm family histories of melanoma whenever possible, despite the practical
      difficulties.

PMID- 10086824
TI  - The Gloucestershire Longitudinal Study of Disability: outcomes in nonresponders,
      responders, and subsequent defaulters.
AB  - Routine health checks of older adults (age > 75 years) are a potential source of
      disability data to inform general practitioners, trusts, and health authorities.
      The value of the data heavily depends on the representativeness of those agreeing
      to the checks. The aim of this study was to determine the outcomes of responders,
      subjects who refused the offer of a health check, and those who defaulted from
      regular health checks after the first year. A sample of 1815 subjects more than
      75 years old, drawn from seven general practices, who started an annual routine
      health check in 1990. All were interviewed by their practice nurse using the
      Elderly At Risk Rating Scale. Survival and hospital admission rates were
      ascertained for responders and refusers. The average age of the responders was
      81.1 (standard deviation [SD] 4.7); for refusers, 80.5 (SD = 7.7); and for
      dropouts, 80.2 (SD = 4.2). In women, the age-adjusted survival was 37.6 months
      (95% confidence interval [CI] 36.3-38.9) in refusers (70% survival) and 39.5
      months (95% CI 38.4-40.6) in responders (73% survival); the respective figures in
      men were 37.4 months (95% CI 35.6-39.1, 67% survival) and 36.8 months (95% CI
      34.9-38.7, 66% survival). Crude mortality rates of responders and the inhabitants
      of areas that matched the locations of the practices were similar. Hospital
      admission rates and mean length of stay were similar in responders and refusers.
      Similarly, those who defaulted did not differ from continued responders in their
      mortality or hospital admission rates. Nonresponders to elderly health checks and
      defaulters have similar health outcomes to responders.

PMID- 10086825
TI  - Serum lipids in postmenopausal or perimenopausal women using estrogen alone,
      estrogen with levonorgestrel, or estrogen with norethisterone, compared with
      nonusers: results from a cross-sectional study in two Norwegian counties 1985
      1988.
AB  - The aim of this study was to compare, in a population setting of postmenopausal
      or perimenopausal women aged 40 to 54, the levels of serum lipids in women using
      different hormone replacement therapy (HRT) regimens with women using no sex
      hormones. There was no unequivocal tendency of a more healthy lifestyle among
      those using HRT than among nonusers. Any type of regimen was associated with a
      lower mean level of total and calculated low-density lipoprotein cholesterol, and
      high-density lipoprotein cholesterol was 0.08 mmol/L (5.2%) higher in those using
      estrogen alone, 0.07 mmol/L (4.5%) higher in users of HRT with norethisterone,
      and 0.07 mmol/L (4.5%) lower in users of HRT with levonorgestrel, compared with
      nonusers. The ratio of total-to-HDL cholesterol was lower by 0.37 (6.1%) in those
      using estrogen alone, by 0.65 (12.3%) in those using HRT with norethisterone, and
      by 0.24 (5.3%) in those using estrogen with levonorgestrel. There was no
      association between body mass index and HDL-cholesterol among women who used HRT
      with norethisterone, whereas an inverse relationship was present in those using
      estrogen alone and in nonusers (P [interaction] < 0.05).

PMID- 10086826
TI  - Effects of multiple attempts to quit smoking and relapses to smoking on pulmonary
      function. Lung Health Study Research Group.
AB  - The effect of intermittent smoking on pulmonary function was assessed among
      participants in the Lung Health Study, 5887 adult smokers with evidence of early
      chronic obstructive pulmonary disease (COPD), followed up for 5 years. The mean
      annual rate of loss in FEV1% of predicted after year 1 was smallest for those who
      quit at some point during the first year of the study and stayed quit (
      0.33%/year, +/-0.05%), intermediate for those who smoked intermittently during
      the study (-0.58%/year, +/-0.05%) and greatest for those who continued to smoke
      throughout the study (-1.18%/year, +/-0.03%). Surprisingly, those who made
      several attempts to quit smoking had less loss of lung function at comparable
      cumulative doses of cigarettes than those who continued to smoke. Quitting
      smoking for an interval followed by relapse to smoking appeared to provide a
      measurable and lasting benefit in comparison to continuous smoking. In this early
      COPD population, not only quitting smoking but attempts to quit smoking can
      prevent some loss of lung function. These results provide some encouragement to
      exsmokers who relapse on their way to complete cessation.

PMID- 10086827
TI  - Estimating the proportion of unnecessary Cesarean sections in Ohio using birth
      certificate data.
AB  - The main objective of the study is to present a method that estimates the
      proportion of unnecessary Cesarean sections (C-sections) using birth certificate
      data. This population-based cross-sectional study uses two major databases--Ohio
      birth certificates and Medicaid eligibility files--and includes singleton infants
      born during the period July 1991 through June 1993 (n = 262,013). A total of 57
      variables indicative of adverse events, including maternal medical risk factors,
      complications of labor and delivery, and congenital anomalies that are available
      on the birth certificate, are examined to estimate the rate of unnecessary C
      sections. The results obtained through this method indicate that nearly 40% of
      the repeat C-sections had no documented abnormalities on the birth certificate to
      justify a C-section. Because studies using medical records have yielded similar
      results, we believe that using birth certificate data may be a reliable method to
      measure and monitor the rate of unnecessary C-sections.

PMID- 10086828
TI  - Health services utilization reporting in respiratory patients. Pharmacy
      Medication Monitoring Program Advisory Board.
AB  - Health services utilization information is important for outcomes research. This
      study assessed the reliability of self-reports of health services utilization in
      respiratory patients. Patients reported health services use and other information
      during three telephone interviews over 6 months. Reports of visits to general
      practitioners (GPs), specialists, emergency room (ER)/clinics, and hospital
      admissions were compared with corresponding fee service claims in the Ontario
      Health Insurance Plan administrative database in 83 subjects. Agreement between
      the two sources was calculated using observed agreement and estimated kappa.
      Substantial agreement was found for hospital admissions and visits to respiratory
      specialists. Agreement was moderate for GP visits and slight for ER/clinic
      visits. Patient self-report of ER use appeared unreliable and may be related to
      imprecise questionnaire wording and inadequately defined fee service codes. The
      findings emphasize the importance of the methods used to assess the reliability
      of patient self-reports used in outcomes research.

PMID- 10086829
TI  - Hospitalizations for aplastic anemia and agranulocytosis in Saskatchewan:
      incidence and associations with antecedent prescription drug use.
AB  - A population-based study to estimate the incidence of hospitalizations for
      aplastic anemia and agranulocytosis and to evaluate associations between these
      disorders and antecedent prescription drug use was performed using the
      Saskatchewan administrative health care databases. Hospital charts and cancer
      registration data were utilized to apply strict diagnostic criteria to case
      identification. Estimates of the annual incidence of aplastic anemia and
      agranulocytosis were 2.7 and 3.0 per million, which are similar to those from
      other recent population-based studies with comparable case identification
      criteria. Only a small number of cases were available to evaluate potential drug
      causes, leading to an analysis of limited power. Nevertheless, significant
      associations were found between aplastic anemia and tocainide, gold salts, and
      antidepressants; and between agranulocytosis and anti-thyroids, trimethoprim
      sulfamethoxazole, beta-lactams, sulfasalazine, chlorpromazine, carbamazepine,
      glyburide, and procainamide, although the associations with antibiotics may
      indicate a response to the disorders rather than a possible cause. These findings
      are generally consistent with the results of other case-control investigations.

PMID- 10086830
TI  - Comparative safety evaluation of non-narcotic analgesics.
AB  - Both spontaneous reports and single outcome studies may distort the overall
      safety evaluation of drugs. We identified epidemiologic studies, published from
      January 1970 to December 1995, that investigated the association of serious
      adverse effects with aspirin, diclofenac, acetaminophen, and dipyrone to
      determine and compare the excess mortality associated with short-term drug use.
      The estimated excess mortality due to community-acquired agranulocytosis,
      aplastic anemia, anaphylaxis, and serious upper gastrointestinal complications
      was 185 per 100 million for aspirin, 592 per 100 million for diclofenac, 20 per
      100 million for acetaminophen, and 25 per 100 million for dipyrone. The estimates
      were largely influenced by the excess mortality associated with upper
      gastrointestinal complications. A relative risk estimate of 300 or more for the
      association of dipyrone with agranulocytosis would have been necessary for the
      excess mortality of dipyrone to be comparable to that of aspirin or diclofenac.
      Based on published epidemiologic evidence used to determine the excess mortality
      associated with short-term use of these four non-narcotic analgesics, the current
      regulatory ranking of the drugs appears inappropriate.

PMID- 10086831
TI  - On subgroups and groping for significance.

PMID- 10086832
TI  - Use of mean residence time to determine the magnitude of difference between rate
      constants and to calculate tmax in the Bateman equation.
AB  - PURPOSE: The goal of this study was to develop a new method, based on robust
      pharmacokinetic (PK) parameters, for determining t(max) (time of peak plasma
      concentration) and the magnitude of difference between the absorption (k(a)) and
      elimination (k) rate constants in the one compartment body model with first order
      input and output. METHODS: The function F(X) that describes the ratio of the AUC
      (area under the curve) from MRT (mean residence time) to infinity and the AUC
      from zero to MRT as a function of ratio between the first-order absorption and
      elimination constants (X) was derived and its limits were determined. Similarly,
      the function G(X) that describes the ratio between MRT and t(max) was derived and
      its limits were determined. RESULTS: The functions F(X) and G(X) depend only on
      the ratio between k and k(a). Thus, the different values of the functions F(X) (a
      values) and G(X) (b-values) were calculated as a function of the ratio k/k(a). A
      table with 1% increments of the relevant b-value for every a-value was derived.
      The appropriate t(max) was thus calculated from the quotient MRT and the relevant
      b-value. A useful application of the new method to a drug product with prolonged
      absorption and long half life was presented. CONCLUSIONS: A new method that
      allows the calculation of t(max) and the k/k(a) ratio and derivation of a simple
      criterion of the equality between k and k(a) has been developed. This method is
      applicable to the one compartment open body model with first order absorption and
      elimination and is not based on single point parameters but on robust
      pharmacokinetic parameters such as AUC and MRT.

PMID- 10086833
TI  - Possible factor for nonlinear pharmacokinetics of TAK-603, a new antirheumatic
      agent, in rats.
AB  - A new antirheumatic, TAK-603, shows nonlinear pharmacokinetics in both animals
      and humans. To elucidate the mechanism of these nonlinear pharmacokinetics, in
      vivo and in vitro metabolism of 14C-labeled TAK-603 ([14C]TAK-603) was studied
      using rats as these resemble humans in their metabolic profiles. After
      intravenous injection of [14C]TAK-603 to rats at doses of 1, 5, and 15 mg kg(-1),
      the total body clearance of unchanged drug decreased significantly with
      increasing dose, whereas the apparent distribution volume did not alter
      remarkably. Thus, saturation in the elimination processes was considered to be a
      factor responsible for the nonlinear pharmacokinetics. The disappearance of
      unchanged drug from the circulation, however, followed a dose-dependent first
      order process, indicating that the nonlinearity observed was not merely due to
      saturation of the elimination capacity. In vitro studies using rat liver
      microsomes showed that TAK-603 competitively inhibited CYP-catalysed nifedipine
      oxidation and also that the demethylated metabolite M-I, the major metabolite in
      rats and humans, competitively inhibited the oxidation of nifedipine. These
      results suggested that inhibition by M-I of the metabolism of the parent drug
      (i.e. product-inhibition) may be the most likely factor responsible for the
      nonlinear pharmacokinetics of TAK-603.

PMID- 10086834
TI  - Bioavailability of carbamazepine from four different products and the occurrence
      of side effects.
AB  - The relative bioavailability of four different carbamazepine products, showing
      large differences in in vitro dissolution profiles, was studied in healthy
      volunteers to correlate the occurrence of side effects with a measure of the rate
      of absorption in vivo for bioequivalence testing. Two of the three generic
      products investigated showed bioequivalence with respect to the extent of
      absorption with Tegretol. In vivo, the differences found in absorption rate were
      reflected in the occurrence of side effects, especially dizziness. As a measure
      for the rate of absorption, the partial AUC did not seem to be a good
      characteristic to test bioequivalence, as the variability is very high and
      dependent on the AUC taken. The Cmax/AUCpart seems more promising, especially the
      partial AUC directly after completion of the absorption process. The variability
      is low in the case of carbamazepine after a single dose. However, as long as no
      consensus on the use of other metrics and the objective (clinical or quality
      control aspects) of bioequivalence testing is reached, and no other
      pharmacokinetic characteristic is validated, Cmax should be the characteristic of
      choice for the rate of absorption in single-dose studies with carbamazepine
      products.

PMID- 10086835
TI  - Intravenous pharmacokinetics and absolute oral bioavailability of dolasetron in
      healthy volunteers: part 1.
AB  - In this first part of a two-part investigation, the intravenous dose
      proportionality of dolasetron mesylate, a 5-HT3 receptor antagonist, and the
      absolute bioavailability of oral dolasetron mesylate were investigated. In an
      open-label, randomized, four-way crossover design, 24 healthy men between the
      ages of 19 and 45 years received the following doses: 50, 100, or 200 mg
      dolasetron mesylate administered by 10-min intravenous infusion or 200 mg
      dolasetron mesylate solution administered orally. Serial blood and urine samples
      were collected for 48 h after dosing. Following intravenous administration,
      dolasetron was rapidly eliminated from plasma, with a mean elimination half-life
      (t1/2) of less than 10 min. Dolasetron was rarely detected in plasma after oral
      administration of the 200 mg dose. Hydrodolasetron, the active primary metabolite
      of dolasetron, appeared rapidly in plasma following both oral and intravenous
      administration of dolasetron mesylate, with a mean time to maximum concentration
      (t(max)) of less than 1 h. The mean t1/2 of hydrodolasetron ranged from 6.6-8.8
      h. The plasma area under the concentration-time curve (AUC0-infinity)) for both
      dolasetron and hydrodolasetron increased proportionally with dose over the
      intravenous dose range of 50-200 mg dolasetron mesylate. Approximately 29-33%)
      and 22% of the dose was excreted in urine as hydrodolasetron following
      intravenous and oral administration of dolasetron, respectively. For dolasetron
      as well as hydrodolasetron, mean systemic clearance (C1), volume of distribution
      (Vd), and t1/2 were similar at each dolasetron dose. The mean 'apparent'
      bioavailability of dolasetron calculated using plasma concentrations of
      hydrodolasetron was 76%. The R(+) enantiomer of hydrodolasetron represented the
      majority of drug in plasma (> 75%) and urine (> 86%). Dolasetron was well
      tolerated following both oral and intravenous administration.

PMID- 10086836
TI  - Single- and multiple-dose pharmacokinetics of oral dolasetron and its active
      metabolites in healthy volunteers: part 2.
AB  - The single- and multiple-dose pharmacokinetics and dose-proportionality of oral
      dolasetron and its active metabolites over the therapeutic dose range was
      investigated in 18 healthy men. In an open-label, randomized, complete three-way
      crossover design, each subject received three separate doses: 50, 100, and 200 mg
      doses of dolasetron mesylate solution given orally. Each dose was administered on
      the morning of Days 1 and 3-7 during each of the three treatment periods. Serial
      blood and urine samples were collected for 48 h after the first and last doses.
      Blood was analysed for dolasetron and hydrodolasetron concentrations; urine was
      analysed for dolasetron, the R(+) and S(-)-enantiomers of hydrodolasetron, and
      the 5'-hydroxy and 6'-hydroxy metabolites of hydrodolasetron. Dolasetron was
      rarely detected in plasma. Hydrodolasetron was formed rapidly, with a time to
      maximum concentration (t(max)) of less than 1 h. Steady-state conditions for
      hydrodolasetron were reached 2-3 days after starting once-daily dosing. Although
      statistical significance was found for hydrodolasetron AUC(0->infinity) and
      C(max) between dose groups after both single and multiple doses of dolasetron,
      the differences were small and unlikely to be of clinical significance. About 17
      22% of the dose was excreted in urine as hydrodolasetron, with the majority (>
      83%) as the R(+) enantiomer.

PMID- 10086837
TI  - Pharmacokinetics and electroencephalographic effects of ketoconazole in the rat.
AB  - To evaluate methodology for in vivo interaction studies of benzodiazepines (BZs)
      and ketoconazole (KCZ) in animal models, this study assessed the pharmacokinetics
      and electroencephalographic (EEG) effect of KCZ, and suitable dosage regimens of
      KCZ to maintain sufficiently high KCZ concentrations to inhibit metabolism of BZs
      in rats. Rats were injected intraperitoneally (i.p.) with KCZ 10 mg kg(-2). No
      significant EEG change was detected regardless of serum KCZ concentration,
      indicating that the EEG changes after both BZ and KCZ administration can be
      attributed entirely to BZ. Serum KCZ concentrations showed an apparent nonlinear
      pattern of decline with a short half-life (1.38 h). An additional dose of 5 mg
      kg(-1) i.p. given 180 min after the initial dose sustained KCZ concentrations
      above 2 pg mL(-1) until at least 500 min after the initial dose. These results
      provide the basis for design of animal models for in vivo assessment of
      interactions of BZs and KCZ.

PMID- 10086838
TI  - Absolute bioavailability of reboxetine enantiomers and effect of gender on
      pharmacokinetics.
AB  - The absolute bioavailability of reboxetine enantiomers was assessed in six male
      and six female volunteers. In a two-way crossover study, subjects received 1.0 mg
      reboxetine orally and 0.3 mg reboxetine as an intravenous bolus. The R,R(-) and
      S,S(+) enantiomers in serial plasma and urine samples were determined by a
      validated LC-MS-MS method. There were no significant differences between
      treatments for clearance or dose-corrected AUC(0-infinity) values. The absolute
      bioavailability was 0.919 and 1.02 for R,R(-) reboxetine and S,S(+) reboxetine,
      respectively. A secondary objective of the study was to assess gender effects on
      pharmacokinetics of the enantiomers. Significant differences in volume of
      distribution between genders were observed, but differences in weight-corrected
      volumes were not significant. Weight-corrected systemic clearance and oral
      clearance tended to be lower in males, but this difference reached statistical
      significance only for weight-corrected oral clearance of R,R(-) reboxetine.
      C(max) after oral administration was 40 and 48% higher in women than men for R,R(
      ) reboxetine and S,S(+) reboxetine, respectively. These results indicate that
      reboxetine enantiomers are well absorbed after oral administration and that
      little first-pass metabolism occurs. There are no clinically significant effects
      of gender on the pharmacokinetics of reboxetine enantiomers.

PMID- 10086839
TI  - Purification and characterization of an intracellular heat-stable proteinase
      (pernilase) from the marine hyperthermophilic archaeon Aeropyrum pernix K1.
AB  - A novel intracellular serine proteinase from the marine aerobic hyperthermophilic
      archaeon Aeropyrum pernix K1 (JCM 9820) that we designated pernilase was purified
      by ammonium sulfate precipitation, anionic-exchange chromatography, affinity
      chromatography, and gel filtration chromatography. The purified enzyme was
      composed of a single polypeptide chain with a molecular mass of 50 kDa as
      determined by SDS-PAGE. The proteinase had a broad pH profile (pH 5-10) with an
      optimum pH of 9.0 for peptide hydrolysis. The optimum temperature for enzyme
      activity was 90 degrees C. The enzyme was strongly inhibited by diisopropyl
      fluorophosphate (DFP) and phenylmethyl sulfonylfluoride (PMSF), suggesting that
      it corresponds to a serine proteinase. The enzyme was highly resistant to the
      reducing agents dithiothreitol and 2-mercaptoethanol but sensitive to the
      denaturing reagents guanidine-HCl and urea and also to the detergent sodium
      dodecyl sulfate (SDS). Pernilase showed high substrate specificity for Boc-Leu
      Gly-Arg-MCA peptide. Thermostability of this enzyme showed half-lives of 85min at
      100 degrees C and 12 min at 110 degrees C.

PMID- 10086840
TI  - Heterologous expression in the Archaea: transcription from Pyrococcus furiosus
      gdh and mlrA promoters in Haloferax volcanii.
AB  - Multicopy plasmids containing the promoter regions for gdh and mlrA genes from
      Pyrococcus furiosus were propagated in Haloferax volcanii. High-level expression
      was detected from gdh promoter sequences, with transcription initiating at the
      same start-site as that found in P. furiosus. For mlrA, several transcripts were
      detected, with one initiating at the P. furiosus start-site; removal or
      disruption of the likely P. furiosus boxA element resulted in the disappearance
      of this transcript, indicating that these sequences were utilized by the H.
      volcanii RNA polymerase for initiation. This is the first demonstration of the
      utilization of promoters from a hyperthermophilic archaeon in a mesophilic
      haloarchaeon and provides further evidence for the unity of transcription
      processes in the domain Archaea.

PMID- 10086841
TI  - An improved physical and genetic map of the genome of alkaliphilic Bacillus sp. C
      125.
AB  - Among alkaliphilic bacteria reported so far, Bacillus sp. C-125 is the strain
      most thoroughly characterized physiologically, biochemically, and genetically. A
      physical map of the chromosome of this strain was constructed to facilitate
      further genome analysis, and the genome size was revised from 3.7 to 4.25Mb.
      Complete digestion of the chromosomal DNA with two rare cut restriction
      endonucleases, AscI and Sse8387I, each yielded 20 fragments ranging in size from
      20 to 600 kb. Seventeen linking clones were isolated in each instance to join the
      adjacent AscI or Sse8387I fragments in the chromosomal map. All AscI linking
      clones isolated were sequenced and analyzed by comparison with the BSORF database
      to map the genes in the chromosome of strain C-125. Several ORFs showing
      significant similarities to those of B. subtilis in the AscI linking clones were
      positioned on the physical map. The oriC region of the C-125 chromosome was
      identified by southern blot analysis with a DNA probe containing the gyrB region.

PMID- 10086842
TI  - Sequencing of three lambda clones from the genome of alkaliphilic Bacillus sp.
      strain C-125.
AB  - The nucleotide sequences of three independent fragments (designated no. 3, 4, and
      9; each 15-20 kb in size) of the genome of alkaliphilic Bacillus sp. C-125 cloned
      in a lambda phage vector have been determined. Thirteen putative open reading
      frames (ORFs) were identified in sequenced fragment no. 3 and 11 ORFs were
      identified in no. 4. Twenty ORFs were also identified in fragment no. 9. All
      putative ORFs were analyzed in comparison with the BSORF database and non
      redundant protein databases. The functions of 5 ORFs in fragment no. 3 and 3 ORFs
      in fragment no. 4 were suggested by their significant similarities to known
      proteins in the database. Among the 20 ORFs in fragment no. 9, the functions of
      11 ORFs were similarly suggested. Most of the annotated ORFs in the DNA fragments
      of the genome of alkaliphilic Bacillus sp. C-125 were conserved in the Bacillus
      subtilis genome. The organization of ORFs in the genome of strain C-125 was found
      to differ from the order of genes in the chromosome of B. subtilis, although some
      gene clusters (ydh, yqi, yer, and yts) were conserved as operon units the same as
      in B. subtilis.

PMID- 10086843
TI  - The mer operon of the acidophilic bacterium Thiobacillus T3.2 diverges from its
      Thiobacillus ferrooxidans counterpart.
AB  - The chromosomal mercury resistance (mer) region of the acidophilic bacterium
      Thiobacillus T3.2 was cloned, characterized, and compared to reported homologous
      sequences. The Thiobacillus T3.2 mer resistance system is organized as an operon
      that transcribes into a polycistronic mRNA encoding the Hg2+ ion transport MerT
      and MerP proteins and the mercuric reductase MerA. In contrast to the
      Thiobacillus ferrooxidans mer determinant, no merC gene was detected.
      Transcription of structural genes is regulated by the product of the regulatory
      merR gene. On the basis of sequence data and expression experiments in E. coli,
      both merTPA and merR transcription units could be located close to each other and
      in different strands, with their promoters (PTPA and PR, respectively)
      overlapping the putative MerR binding site in the intergenic operator/promoter
      (O/P) region. Amino acid sequences of mer gene products were compared to their
      homologs. Some sequence features, such as the number and position of cysteine
      residues, are unique for the Mer proteins of this bacterium. Similarities (-10
      and -35 boxes are 19bp apart in both PR and PTPA promoters) and differences
      (inverted repeats in the Thiobacillus T3.2 MerR-binding site are 2bp shorter than
      in Thiobacillus ferrooxidans) exist between the O/P intergenic regions of both
      Thiobacilli. In vivo experiments showed inducible expression of mercury
      resistance in E. coli cells transformed with the entire Thiobacillus T3.2 mer
      genetic determinant (structural plus regulatory genes), and little or no
      expression in clones containing only the structural merT, merP, and merA genes.

PMID- 10086844
TI  - Degradation of 3-phenylpropionic acid by Haloferax sp. D1227.
AB  - Haloferax sp. D1227, isolated from soil contaminated with highly saline oil
      brine, is the first halophilic archaeon to demonstrate the utilization of
      aromatic compounds (i.e., benzoic acid, cinnamic acid, and 3-phenylpropionic
      acid) as sole carbon and energy sources for growth. The degradation of 3
      phenylpropionic acid in this strain was studied to examine the strategies
      utilized by Archaea to metabolize aromatic compounds. Based on our findings of
      (1) the extracellular accumulation of cinnamic acid, benzoic acid, 3
      hydroxybenzoic acid, and gentisic acid in cultures of Haloferax D 1227 grown on 3
      phenylpropionic acid, (2) the presence of an 3-phenylpropionylCoA dehydrogenase,
      (3) the ATP, CoA, and NAD-dependent conversion of cinnamic acid to benzoylCoA,
      and (4) the presence of gentisate 1,2-dioxygenase, we propose that Haloferax
      D1227 metabolizes 3-phenylpropionic acid by initial 2-carbon shortening of the
      side chain to benzoylCoA via a mechanism similar to fatty acid beta-oxidation,
      followed by aromatic degradation using a gentisate pathway. The upper aliphatic
      pathway from 3-phenylpropionic acid to benzoic acid is regulated separately from
      the lower gentisate pathway.

PMID- 10086845
TI  - Thermococcus siculi sp. nov., a novel hyperthermophilic archaeon isolated from a
      deep-sea hydrothermal vent at the Mid-Okinawa Trough.
AB  - A novel coccoid-shaped, hyperthermophilic, anaerobic archaeon, strain RG-20, was
      isolated from a deep-sea hydrothermal vent fluid sample taken at 1394-m depth at
      the Mid-Okinawa Trough (27 degrees 32.7'N, 126 degrees 58.5'E). Cells of this
      isolate occur singly or in pairs and are about 0.8 to 2 microm in diameter.
      Growth was observed at temperatures between 50 degrees and 93 degrees C, with an
      optimum at 85 degrees C. The pH range for growth is 5.0-9.0, with an optimum
      around 7.0. Strain RG-20 requires 1%-4% of NaCl for growth, and cell lysis occurs
      at concentrations below 1%. The newly isolated strain grows preferentially in the
      presence of elemental sulfur on proteinaceous substrates such as yeast extract,
      peptone, or tryptone, and no growth was observed on carbohydrates, carboxylic
      acids, alcohols, or lipids. This microorganism is resistant to streptomycin,
      chloramphenicol, ampicillin, and kanamycin at concentrations up to 150 microg/
      ml, but is susceptible to rifampicin. Analysis of the hydrolyzed core lipids by
      thin-layer chromatography (TLC) revealed the presence of archaeol and
      caldarchaeol. The mol% G+C content of the DNA is 55.8. Partial sequencing of the
      16S rDNA indicates that strain RG-20 belongs to the genus Thermococcus.
      Considering these data and on the basis of the results from DNA-DNA hybridization
      studies, we propose that this strain should be classified as a new species named
      Thermococcus siculi (si'cu.li. L. gen. n. siculi, of the deep-sea [siculum, deep
      sea in literature of Ovid], referring to the location of the sample site, a deep
      sea hydrothermal vent). The type strain is isolate RG-20 (DSM No. 12349).

PMID- 10086846
TI  - Dissimilatory sulfite reductase from Archaeoglobus profundus and Desulfotomaculum
      thermocisternum: phylogenetic and structural implications from gene sequences.
AB  - The genes encoding the alpha- and beta-subunits of dissimilatory sulfite
      reductase, dsrAB, from the hyperthermophilic archaeon Archaeoglobus profundus and
      the thermophilic gram-positive bacterium Desulfotomaculum thermocisternum were
      cloned and sequenced. The dsrAB genes are contiguous, and most probably comprise
      an operon also including a dsrD homolog, a conserved gene of unknown function
      located downstream of dsrAB in all four sulfate reducers so far sequenced.
      Sequence comparison confirms that dissimilatory sulfite reductase, Dsr, is a
      highly conserved enzyme. A phylogenetic analysis using the available Dsr
      sequences, including Dsr-like proteins from nonsulfate reducers, suggests a
      paralogous origin of the alpha- and beta-subunits. Furthermore, the Dsr from
      sulfate reducers forms a separate cluster, with Dsr from the bacterial sulfate
      reducers Desulfotomaculum thermocisternum and Desulfovibrio vulgaris branching
      together, next to Dsr from Archaeoglobus profundus and Archaeoglobus fulgidus.
      Based on an alignment with the assimilatory sulfite reductase from Escherichia
      coli, the amino acid residues involved in binding of sulfite, siroheme, and
      [Fe4S4]-clusters have been tentatively identified, which is consistent with the
      binding of two sirohemes and four [Fe4S4]-clusters per alpha2beta2 structure. The
      evolution of Dsr and the structural basis for the binding of substrate and
      cofactors are discussed.

PMID- 10086847
TI  - Taxonomic studies of extremely barophilic bacteria isolated from the Mariana
      Trench and description of Moritella yayanosii sp. nov., a new barophilic
      bacterial isolate.
AB  - We have isolated two strains of extremely barophilic bacteria from sediment
      collected from the world's deepest ocean floor in the Mariana Trench, Challenger
      Deep, at a depth of 10898m [Kato C, Li L, Nogi Y, Nakamura Y, Tamaoka J,
      Horikoshi K (1998) Appl Environ Microbiol 64:1510-1513]. One strain, DB21MT-2,
      was identified as a strain of Shewanella benthica, and the other strain, DB21MT
      5, is closely affiliated with members of the genus Moritella on the basis of 16S
      rDNA sequence analysis. The hybridization values for DNA-DNA relatedness between
      DB21MT-5 and the Moritella reference strains were significantly lower than that
      accepted as the phylogenetic definition of a species. Based on this and other
      taxonomic differences, strain DB21MT-5 appears to represent a novel obligately
      barophilic deep-sea Moritella species. The name Moritella yaynanosii (JCM 10263)
      is proposed. This is the first proposed species of obligately barophilic bacteria
      of the genus Moritella.

PMID- 10086848
TI  - The case against micrographically controlled skin surgery.

PMID- 10086849
TI  - Interleukin-8 plays its role at local level in psoriasis vulgaris.
AB  - The pro-inflammatory properties of interleukin-8 (IL-8) suggest a major role of
      this peptide in inflammatory processes of skin and other organs. Both biochemical
      and immunohistochemical studies from our group have demonstrated IL-8 peptide
      within psoriatic scales and epidermis. So far, however, the relevance of
      circulating IL-8 and its relation to locally produced IL-8 in this disease remain
      unclear. Serum IL-8 levels of psoriatic patients were determined in sandwich
      ELISA prior to therapy as well as during therapy. Using either the assay from our
      laboratory or three commercial ELISAs, no correlation was found between serum IL
      8 levels and disease severity at any stage of the disease. Similarly, epidermal
      IL-8-immunoreactivity was monitored immunohistochemically in sequential biopsies
      from individual psoriatic lesions as they resolved during the course of therapy.
      Initially, decreased epidermal IL-8 immunoreactivity shifted to a homogeneous
      staining comparable to normal or non-diseased skin as lesions resolved under
      treatment. These results indicate a role of IL-8 at local level in psoriatic
      skin. In contrast to hyperinflammatory diseases like sepsis, where increased
      serum IL-8 levels are found, in psoriasis either circulating IL-8 is absent or
      potent mechanisms are operative effectively binding and/or inactivating IL-8 as
      it enters circulation.

PMID- 10086850
TI  - Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic
      mechanism for psoriasis.
AB  - Intraepidermal collections of neutrophils and lymphocytes are unique features of
      the inflammatory reaction of psoriasis. Migration of leukocytes from dermis to
      the epidermis suggests a role for chemotactic agent(s). In recent years,
      increased levels of chemokines such as IL-8 , GRO-a and MCP-1 have been reported
      in the keratinocytes of psoriatic tissue. IL-8 and GRO-alpha belong to a
      subfamily (C x C) class and MCP-1 is a beta chemokine. In this study, we
      investigated RANTES, which is a beta chemokine (C-C class); RANTES has been found
      to be associated with various cell-mediated hypersensitive disorders. We obtained
      eight skin biopsies from chronic psoriatic plaques, and five biopsies each from
      non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from
      healthy controls. Snap-frozen samples were cut into 7 microm cryosections and
      stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA).
      Standard immunohistochemistry techniques were applied. RANTES was detected only
      in the keratinocytes. The number of keratinocytes in per mm2 of epidermis stained
      for RANTES were 116.79+/-98.42 in psoriatic tissues compared to 32.00+/-46.05
      (p<0.05), 6.39+/-3.59 (p<0.01), 2.64 +/-1.15 (p<0.01) and 3.53+/-5.26 (p<0.01),
      respectively, in the non-lesional, lichen planus, eczematous lesions and normal
      skin. This is the first study to report that the keratinocytes of psoriatic
      tissue express high levels of RANTES compared to the controls. IL-8 and related
      molecules (C x C class) are predominantly chemotactic for neutrophils and MCP-1
      is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic
      for memory T cells and activated naive T cells. Increased amounts of RANTES as
      reported here provide an explanation for migration of the activated T cells to
      the epidermis of the psoriatic lesions. In addition, RANTES activates T cells.
      These results suggest that RANTES may have a significant role in the inflammatory
      process of psoriasis. Our findings further substantiate a regulatory role for
      keratinocytes in the inflammatory process of psoriasis.

PMID- 10086851
TI  - Elemental analysis mirrors epidermal differentiation.
AB  - Using a scanning nuclear microprobe, the distribution of elements and trace
      elements of skin cross sections of normal skin, non-lesional psoriatic skin and
      in dry atopic skin have been mapped. In non-lesional psoriatic skin and in dry
      atopic skin the epidermal Ca-gradient is higher than that of normal skin. In
      addition, abnormally high Fe and Zn levels were recorded in the stratum
      granulosum and corneum regions in the pathological skin. It is suggested that
      these findings correlate to an increased cell turnover in the basal cell layer of
      the psoriatic and atopic skins. The ratio of Ca/Zn in stratum corneum of
      paralesional psoriatic skin is approximately 8:1 compared to 12: 1 in normal skin
      and 15: 1 in atopic skin. This suggests that the differentiation process in
      paralesional psoriatic skin may actually be an example of disturbed programmed
      cell death.

PMID- 10086852
TI  - In vitro release of interferon-gamma and macrophage migration inhibition factor
      in drug-induced urticaria and angioedema.
AB  - T-cells are involved in the pathogenesis of cutaneous drug reactions. T-cell
      phenotype and cytokine release pattern in rivo and in vitro might correlate with
      the type of immune response involved in cutaneous drug reactions. In vitro
      release of interferon-gamma and macrophage migration inhibition factor (MIF) from
      peripheral blood lymphocytes, following in vitro challenge with the suspected
      unmodified drugs, was studied in 12 patients with drug-induced urticaria and/or
      angioedema and in two group-matched controls. The occurrence of positive
      interferon-gamma and MIF responses was significantly higher in patients with drug
      induced urticaria and/or angioedema than in controls. The sensitivity and
      specificity of the interferon-gamma test (50% and 92%, respectively) were similar
      to that of the MIF test (58% and 96%, respectively). Percentage agreement between
      both tests was 80.9 (kappa = 0.76). In vitro release of interferon-gamma and MIF
      in drug-induced urticaria and/or angioedema suggests a drug-specific immune
      response, and may implicate the drug as a possible inducer of the reaction.

PMID- 10086853
TI  - Effect of intradermal injection of methionine-enkephalin on human skin.
AB  - Methionine-enkephalin (met-enk) detected in monocytes in psoriatic skin can
      modulate inflammatory processes and keratinocyte differentiation/proliferation in
      vitro. The purpose of the present study was to determine the effect of
      intradermal injection of met-enk on normal human skin and on the development of a
      delayed type skin hypersensitivity reaction. In 6 healthy volunteers, 50 microl
      of met-enk (16, 30, and 45 nmol) was injected once in the forearm and the
      reaction was evaluated clinically and by video-optical recording for 120 min.
      Compared to vehicle (0.9% saline), met-enk induced a time- and dose-dependent
      flare reaction, but no significant stimulation of a weal reaction. The flare
      reaction was maximal after 1 min and disappeared within 45 min. Pre-treatment
      with the antihistamine cetirizine reduced the flare reaction. Furthermore, the
      effect of met-enk on lymphocyte/monocyte infiltration and epidermal proliferation
      in normal skin and on a delayed type skin hypersensitivity reaction was assessed.
      Met-enk (45 nmol/ 50 microl) was injected at 0, 24 and 48 h. In normal skin, met
      enk increased the number of dermal lymphocytes/monocytes (CD3/CD68 positive
      cells) and the degree of epidermal proliferation (MIBI-Ki67). In a delayed type
      hypersensitivity reaction induced by tuberculin (PPD), the degree of epidermal
      proliferation and the number of infiltrating lymphocytes/monocytes were reduced
      compared to PPD alone. Our study suggests that intradermal injection of met-enk
      in normal human skin induces an inflammatory reaction that may involve the
      release of histamine. In contrast, met-enk seems to down-regulate the development
      of a delayed type skin hypersensitivity reaction. These results may indicate that
      the direction of the effect of the opioid peptide met-enk on human skin depends
      on the rate of epidermal proliferation and the activity of immunocompetent cells.

PMID- 10086854
TI  - Expression of the adhesion molecules ICAM-1, VCAM-1, LFA-1 and VLA-4 in the skin
      is modulated in progressing stages of chronic venous insufficiency.
AB  - In inflammation and wound healing, dynamic changes in cell adhesion and migration
      are fundamental properties of the cells involved. Disturbed interaction of
      leukocytes with microvascular endothelial cells has been proposed to be a central
      pathogenic factor in chronic venous insufficiency. This disease may therefore
      serve to elucidate dysregulated modulation of adhesion molecule expression in
      conditions of chronic inflammation and impaired wound healing. In this study, we
      determined how the expression of ICAM-1/VCAM-1 on endothelial cells and their
      ligands LFA-1/VLA-4 on leukocytes is modulated in skin of progressing stages of
      chronic venous insufficiency. Immunohistochemical staining of skin biopsies
      revealed an increase in the expression of ICAM-1 and VCAM-1 on endothelial cells
      in an early stage of venous disease such as stasis dermatitis. Such protein
      expression correlated with an increase of corresponding mRNA in skin biopsies.
      Expression of these CAMs on endothelial cells was accompanied by the occurrence
      of a marked perivascular infiltration of leukocytes, which expressed increased
      levels of LFA-1 and VLA-4. In progressing stages of chronic venous insufficiency,
      characterized by hyperpigmentation and lipodermatosclerosis, which precede skin
      ulceration, all these CAMs remained upregulated on endothelial cells and
      infiltrating leukocytes. Our findings indicate that following an initial peak
      expression during stasis dermatitis, vascular ICAM-1 and VCAM-1 expression is not
      downmodulated to baseline levels, but remains upregulated. This possibly promotes
      tissue damage by a perpetuated, upregulated influx of activated leukocytes,
      finally leading to skin ulceration.

PMID- 10086855
TI  - Thermophysical effects of ointments in cold: an experimental study with a skin
      model.
AB  - The use of emollients on the face is a traditional way to protect the skin
      against cold injuries in cold climate countries like Finland, but their
      preventive effect against frostbite has been questioned. The purpose of this
      investigation was to define the thermal insulation and occlusivity of ointments
      in cold by using a skin model with a sweating hot plate. The properties of four
      different emollients were studied in both dry and humid conditions simulating
      transepidermal water loss, sweating, and a combination of sweating and drying.
      The thermal insulation of ointments applied on a dry surface was minimal.
      Evaporation of water from an oil-in-water cream caused significant cooling for 40
      min after its application. The diffusion of water through the applied emollients
      changed their thermal effects depending on their composition and on the amount of
      water. Low input of water increased and high input diminished slightly the
      thermal resistance of ointments. The minimal or even negative thermal insulation
      of emollients in varying conditions gives them at best only a negligible and at
      worst a disadvantageous physical effect against cold.

PMID- 10086856
TI  - Interleukin-15 is not a constitutive cytokine in the epidermis, but is inducible
      in culture or inflammatory conditions.
AB  - The regulation in the skin of interleukin-15 (IL-15), a potent modulator of T
      cell-mediated immune responses, is not fully understood. We investigated the
      levels of IL-15 and its mRNA produced by epidermal and cultured keratinocytes and
      found that normal keratinocytes did not constitutively express IL-15 in the
      epidermis, but in culture began to produce the cytokine. Some epidermal
      keratinocytes expressed IL-15 in inflammatory conditions associated with
      infiltration of neutrophils and eosinophils. IL-15 was detected only in the cell
      lysates, not in the supernatants of cultured keratinocytes. Dexamethasone (10(-5)
      10(-6) M) markedly inhibited IL-15 mRNA expression by normal and transformed
      keratinocytes in a range of pharmacological concentrations. IFN-gamma (200 and
      400 U/ml) slightly increased the IL-15 message level in a squamous cell carcinoma
      cell line, HSC-5, in a dose-dependent fashion, whereas no significant change was
      observed in cultured normal human keratinocytes. Our data indicate that IL-15 is
      not a constitutive cytokine in epidermal keratinocytes but is inducible.

PMID- 10086857
TI  - Further evidence of genetic homogeneity in Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by
      congenital ichthyosis, spastic di- or tetraplegia and mental retardation. In 1994
      Sjogren-Larsson syndrome was mapped to chromosome 17, close to the genetic marker
      D17S805 in a study of 24 Swedish families. We have analysed 12 microsatellite
      markers in 10 additional non-Swedish families with Sjogren-Larsson syndrome
      originating from Germany, Lebanon, Spain and Canada. The results are consistent
      with earlier data and give further evidence of Sjogren-Larsson syndrome being a
      homogeneous disorder. Swedish soldiers were bivouacking in Germany during the 30
      year war in the 17th century and it has been suggested that they could have
      introduced the Sjogren-Larsson syndrome gene to the German population. Haplotypes
      from 7 German families with Sjogren-Larsson syndrome were compared with earlier
      analysed Swedish haplotypes. No evidence of all German patients carrying the same
      mutation or the major "Swedish Sjogren-Larsson syndrome gene" was found.

PMID- 10086858
TI  - Somatostatin- and factor XIIIa-immunoreactive cells in psoriasis during
      clobetasol propionate and calciprotriol treatment.
AB  - This study describes the changes in number and distribution of somatostatin- and
      factor XIIIa-immunoreactive dendritic cells in the epidermis and dermis of
      psoriatic lesional skin during topical treatment with clobetasol propionate or
      calcipotriol. Immunohistochemical analysis showed that the number of each cell
      type was increased in lesional skin as compared to normal skin. Investigation of
      serial biopsies from psoriasis lesions revealed a significant reduction in the
      number of somatostatin- and factor XIIIa-positive dendritic cells during the
      treatments. The reduction rate of the somatostatin-positive cells differed
      between the two groups and closely paralleled the healing process induced by the
      two treatments. These findings and the fact that somatostatin has been used in
      several studies as treatment for psoriasis may indicate that the somatostatin
      positive cells are specifically involved in the healing process of psoriasis. The
      reduction of the factor XIIIa-positive cells was associated with the healing
      process as a whole, but showed no relation to either treatment.

PMID- 10086859
TI  - Effect of long-term use of moisturizer on skin hydration, barrier function and
      susceptibility to irritants.
AB  - Moisturizers are often used in the prevention and treatment of irritant contact
      dermatitis. The present study was to determine whether long-term daily use of a
      moisturizer on normal skin would affect skin barrier function, hydration state,
      or susceptibility to sodium lauryl sulphate. Healthy volunteers used a
      moisturizer on one forearm 3 times daily for 4 weeks. The other forearm served as
      a control. Afterwards both forearms were challenged with a patch-test of sodium
      lauryl sulphate. Skin barrier function was evaluated by measuring trans-epidermal
      water loss and skin hydration by measuring electrical capacitance. Electrical
      capacitance was significantly increased on the treated arm during the treatment
      period. After challenge with sodium lauryl sulphate, transepidermal water loss
      was significantly higher on the arm treated with moisturizer than on the control
      arm. The results suggest that long-term treatment with moisturizers on normal
      skin may increase skin susceptibility to irritants.

PMID- 10086860
TI  - "Endonyx" onychomycosis: a new modality of nail invasion by dermatophytes.
AB  - Three patients with onychomycosis due to Trichophyton soudanense with an
      "endonyx" type of nail invasion are presented. Endonyx onychomycosis is
      clinically characterized by a diffuse milky-white discolouration of the affected
      nail, in the absence of nail bed hyperkeratosis or onycholysis. Nail plate
      surface and nail thickness are normal. The pathology shows a contrast between the
      great number of fungal hyphae visible in the nail plate and the absence of fungal
      elements in the nail bed. The nail bed does not show inflammatory changes or
      hyperkeratosis and adheres strictly to the lowermost layers of the nail plate.
      The hyponychium is normal and does not contain hyphae. The endonyx pattern of
      nail infection appears to be specific to T. soudanense nail invasion and may
      possibly reflect the high affinity of T. soudanense to hard keratins.

PMID- 10086861
TI  - In vivo detection of basal cell carcinoma using imaging spectroscopy.
AB  - Photodynamic therapy has become an interesting alternative to conventional
      therapy for basal cell carcinomas. Delta-aminolevulinic acid is a precursor in
      the biosynthesis of protoporphyrin IX that accumulates to a large extent in
      tumour tissue. We have compared in vivo protoporphyrin IX fluorescence with the
      extent of basal cell carcinomas on the face, trunk and thigh determined by
      histological mapping in 30 lesions in 22 patients. A new non-laser based set-up
      was used to record the fluorescence images. Delta-aminolevulinic acid was applied
      for 4 h inducing high concentrations of protoporphyrin IX. Routine vertical
      histological sections and Mohs micrographic surgery were used to map the extent
      of the tumours. In 50% of lesions we found a good correlation between the
      fluorescence imaging and histological mapping. In 23% the correlation was
      partial. In the other lesions we found no correlation at all. This method may be
      used to delineate basal cell carcinomas more accurately than current methods.

PMID- 10086862
TI  - Fibromyalgia in lupus erythematosus.
AB  - Fibromyalgia has been reported to occur with high prevalence in systemic lupus
      erythematosus. Data on fibromyalgia in other subsets of lupus erythematosus are
      not available. Risk factors for fibromyalgia have not been defined. We
      investigated 60 patients with different subsets of lupus erythematosus for the
      presence of fibromyalgia, association with clinical and laboratory parameters and
      disease activity. Our data were compared with the multicentre lupus erythematosus
      registry at the Free University of Berlin. Ten out of 60 patients with more than
      11 tender points and widespread pain for more than 3 months were classified as
      positive for fibromyalgia. All of them were female. Fibromyalgia-positive
      patients suffered significantly more often from headache, morning stiffness,
      diffuse alopecia, muscle pain, arthralgia, renal involvement, and disclosed
      peripheral blood cell cytopenia, rheumatoid factor, hypergammaglobulinaemia and
      intake of corticosteroids and azathioprine. Fibromyalgia was more frequent in
      systemic lupus than in other lupus subsets. Evaluation of fibromyalgia symptoms
      and lupus disease activity was performed in 30 patients in a 1-year (range 9-13
      months) follow-up. These 30 patients consisted of 9 fibromyalgia-positive and 21
      fibromyalgia-negative patients. Both groups were characterized by stable clinical
      features such as number of tender points and ECLAM index. Fibromyalgia did not
      show a correlation with lupus activity. We suggest that fibromyalgia and lupus
      erythematosus are distinct complaints. Patients with lupus are at risk of
      developing secondary fibromyalgia. The clinical features of fibromyalgia-positive
      patients may contribute to misinterpretation of lupus activity.

PMID- 10086863
TI  - Erythrosis pigmentosa mediofacialis (Brocq) and erythromelanosis follicularis
      faciei et colli in the same patient.
AB  - Erythrosis pigmentosa peribuccalis (Brocq) (or erythrosis pigmentosa
      mediofacialis) and erythromelanosis follicularis faciei et colli, have been
      regarded as different disorders, mainly because the first occurs on the
      mediofacial area and is common in women and the second mostly occurs pre
      auricularly in men. Both conditions show histological signs of abnormal
      follicular keratinization with teleangiectasia and round cell infiltrate. An
      increase in the level of melanin has been seen in some patients. We describe here
      a woman in whom lesions started in the middle of the face and later became
      evident in the pre-auricular area. This suggests that the two conditions are in
      fact the same disease. As a neutral term for this not uncommon disorder we
      propose erythrosis pigmentosa faciei et colli.

PMID- 10086864
TI  - Cold protecting ointments and frostbite. A questionnaire study of 830 conscripts
      in Finland.
AB  - Application of ointments to the face is one of many measures used to avoid
      frostbite of the head in cold climates. A recent epidemiological study indicated,
      however, that the use of ointments in the cold may be a considerable risk factor
      in development of frostbite of the face and ears. A questionnaire on the use of
      protective ointments was completed by 830 young male conscripts divided into 4
      groups by climatic home region on the south - north axis of Finland. Personal
      estimates of cold exposure, sensitivity to cold, smoking, and cumulative
      incidence of frostbite to the face and ears were reported. Twenty-one percent of
      the conscripts had used cold protective ointments, mostly at school age or
      earlier. In 25% of the conscripts' families some other member (mostly women and
      children) had used emollients in order to prevent cold injuries. Both the
      conscripts and their families living in southern Finland used protective
      ointments more often than those in northern Finland. Almost half (47%) of the
      conscripts had had frostbites of the head, 42% of the ears and 23% of the face.
      Those who had used ointments in the cold had a significantly higher cumulative
      incidence of frostbites on the face (p=0.0031), especially on the cheeks and
      chin. Their subjective experience concerning the protective effect of ointments
      in the cold was somewhat or clearly positive in 84% of respondents. The
      controversy between subjective experience and increased incidence of facial
      frostbite in ointment users needs further investigation.

PMID- 10086865
TI  - Percutaneous and combined percutaneous and intralesional Nd:YAG-laser therapy for
      vascular malformations.
AB  - The numerous types of vascular abnormality are classified in groups according to
      their pathological and anatomical features. We present case histories of 2
      patients who had vascular malformations of the face since birth or early
      childhood. Application methods, side-effects and complications of percutaneous
      and intra-lesional Nd:YAG-laser therapy are reviewed for these patients. A 54
      year-old woman was treated percutaneously with the Nd: YAG-laser at 1064 nm, with
      20 30 W, cw 1-5 s pulses and 2 - 3 mm spot size. A 59-year-old woman was treated
      with the combined percutaneous and intralesional laser therapy with 30 W, cw 1-5
      s pulses and 2-3 mm spot size. In both cases, percutaneous or combined
      percutaneous and intra-lesional Nd: YAG-laser application resulted in a
      significant shrinking of the lesion. The Nd:YAG-laser radiation at 1064 nm
      presents an effective treatment of vascular malformations due to its deep
      penetration into the tissue. No standardized guidelines for Nd: YAG-laser therapy
      exist and the treatment parameters should be chosen individually according to the
      type of vascular malformation.

PMID- 10086866
TI  - Eye and hair colour, skin type and constitutive skin pigmentation as risk factors
      for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control
      study.
AB  - To assess the importance of hair and eye colour, skin type and constitutive skin
      pigmentation as risk factors for basal cell carcinoma and cutaneous malignant
      melanoma in fair-skinned Caucasians, we conducted two identical case-control
      studies in Denmark. We studied 145 cases with basal cell carcinoma and 174
      matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched
      controls. Controls were matched on age, gender and place of residence. Subjects
      indicated their hair colour before 7 years of age, and at 25 years of age and
      their skin phototype. Interviewers assessed the present hair colour and eye
      colour, and the constitutive skin pigmentation was measured objectively by skin
      reflectance of UV unexposed buttock skin. There were no differences between basal
      cell carcinoma cases and controls in hair colour or eye colour or constitutive
      skin pigmentation, but more cases were of skin type II than skin type IV; skin
      type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of
      2.3. For cutaneous malignant melanoma, more cases than controls were red-haired
      or blond and of skin type II, but there was no difference in constitutive skin
      pigmentation. Hair colour and skin type were found to be independent risk factors
      for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair
      vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no
      gender-related differences in risk factors for basal cell carcinoma and cutaneous
      malignant melanoma.

PMID- 10086867
TI  - Proximal white subungual onychomycosis in the immunocompetent patient: report of
      two cases and review of the literature.

PMID- 10086868
TI  - Ring-induced nail pitting?

PMID- 10086869
TI  - Fox-Fordyce disease: two cases in patients with Turner syndrome.

PMID- 10086870
TI  - Successful treatment of generalized granuloma annulare with polyethylene sheet
      bath PUVA.

PMID- 10086871
TI  - Hypercalcaemia and hypercalciuria after topical treatment of psoriasis with
      excessive amounts of calcipotriol.

PMID- 10086872
TI  - Low dose cyclosporin A and methotrexate in the treatment of psoriasis.

PMID- 10086873
TI  - Epidermal inclusion cyst with melanoma-like melanophagic proliferation.

PMID- 10086874
TI  - Histamine intolerance imitated a fish allergy.

PMID- 10086875
TI  - Zosteriform cutaneous metastases arising from adenocarcinoma of the colon:
      diagnostic smear cytology from cutaneous lesions.

PMID- 10086876
TI  - Erythema elevatum diutinum in a patient with human herpesvirus 6 infection.

PMID- 10086877
TI  - Graham Little-Piccardi-Lasseur syndrome following HBV vaccination.

PMID- 10086878
TI  - Discordance between DNA analysis and the clinical picture in a case of xeroderma
      pigmentosum.

PMID- 10086879
TI  - Post-herpes zoster scar sarcoidosis.

PMID- 10086880
TI  - Alkaline phosphatase activity in human periodontal ligament: age effect and
      relation to cementum growth rate.
AB  - Recently, a relationship was demonstrated between the thickness of the cementum
      layer in rat molars and the activity of alkaline phosphatase (ALP) in the
      adjoining periodontal ligament (PDL). It was the aim of the present study to
      investigate whether such a relationship also exists in the periodontium of man.
      Healthy deciduous and permanent teeth free from periodontitis were obtained from
      74 patients, varying in age from 3 to 78 yr, and their PDL dissected from the
      middle one-third of the roots. ALP activity was measured in PDL extracts and
      expressed per hydroxyproline content. It was shown that ALP activity was
      relatively high in children. After puberty its concentration decreased to level
      off at about half the concentration found in the younger age groups. The activity
      of the enzyme in the PDL correlated positively with the yearly cementum thickness
      increment as calculated from data published previously.

PMID- 10086881
TI  - Cyclosporin A-induced gingival overgrowth in the rat: a histological,
      ultrastructural and histomorphometric evaluation.
AB  - This investigation was undertaken to further study cyclosporin A (CsA)-induced
      gingival overgrowth. Thirty mg/kg/d of vehicle or CsA solutions were given orally
      to 6-wk-old male Sprague-Dawley rats. After 4, 9, 14 and 19 wk 2 control and 2
      experimental rats were anaesthetized, tissues fixed by intracardiac perfusion of
      fixative solution and jaws processed for Epon inclusion. Histological and
      ultrastructural studies conducted in a gingival portion (free gingiva) revealed
      the presence of hyalinization areas and of multinucleated cells (MCs) containing
      collagen fibrils (connective tissue), of amorphous areas and disorders of
      keratinization (epithelia). Histomorphometric evaluation indicated that in the
      CsA rats the mean cross-sectional area of the free gingiva was 2.52-fold
      increased compared to the controls. The connective tissue comprised 41.43% of
      this area (instead of 31.49% in controls). Additional histomorphometric
      evaluation was performed in 3 groups of free gingival portions: control (C
      group), CsA-non-respondent (CsA-nR) and CsA-respondent (CsA-R). The cross
      sectional gingival areas studied were slightly lower than the mean area of all
      the control sites previously defined (groups C and CsA-nR) or showed the higher
      degrees of enlargement (CsA-R). In the CsA-R group the mean cross-sectioned area
      of the vessel profiles was increased and the number of fibroblast profiles
      decreased. In the CsA-nR group the number of vessel profiles and that of MCs
      profiles were increased. In the epithelia of the CsA-R group were increased (a)
      keratinized epithelia: thickness; thickness of the inner and of the outer
      compartments; surface area of spinous cell profiles; (b) oral gingival
      epithelium: number of cell layers (inner compartment); (c) oral sulcular
      epithelium: surface area of granular cell profiles; (d) junctional epithelium:
      thickness; number of cell layers. These results indicate that (a) the CsA induced
      modifications are not limited to enlarged gingiva (b) the overgrowth of the GCT
      is the result of a vasodilatation and of an increase in the volume of the
      extracellular matrix and (c) the increase of the epithelial thickness is mainly
      the result of a cell hypertrophy in the keratinized epithelia and of a cell
      hyperplasia in the junctional epithelium.

PMID- 10086882
TI  - Evidence that laminin-5 is a component of the tooth surface internal basal
      lamina, supporting epithelial cell adhesion.
AB  - Laminin-5 (Ln-5) is an extracellular matrix (ECM) glycoprotein found in
      epithelial basal laminae. We studied its expression on the surface of rat molars,
      in relationship to the location of the internal basal lamina (IBL) of the
      junctional epithelium (JE). In order to avoid disruption of the JE-tooth
      interface as much as possible, the surface of molars was prepared by mechanical
      removal of tissue debris and detergent/osmotic lysis of epithelial cell layers,
      and directly stained by immunohistochemistry, without sectioning. Antibodies to
      Ln-5 specifically stained a narrow band in the region of the cemento-enamel
      junction (CEJ), consistent with the expected location of the IBL. Western
      blotting of ECM material detergent--solubilized from the prepared tooth surfaces
      confirmed the molecular nature of Ln-5 identified by immunohistochemistry. By the
      use of a high-definition 3-D microscope, it appeared that Ln-5 coated the most
      apical part of the enamel and the most coronal portion of the cementum, on either
      side of the CEJ. In adhesion assays performed directly on tooth surfaces,
      epithelial cells adhered preferentially to the Ln-5 coated area of the tooth
      compared to the root surface, which is coated by other ECM components. Adhesion
      to the Ln-5 coated surface was specifically inhibited by a function-blocking
      monoclonal antibody to Ln-5. These results suggest that Ln-5 is a component of
      the IBL, and that it may be important in promoting adhesion of JE cells onto the
      tooth surface.

PMID- 10086883
TI  - Clinical and microbiological characteristics of smokers with early onset
      periodontitis.
AB  - Cigarette smoking is a potential risk factor which has recently been associated
      with periodontal disease progression. The objective of this study was to compare
      the microbial profile of smokers and non-smokers in a group of patients with
      early onset periodontitis. The study population consisted of 60 healthy
      individuals, 40 males and 20 females aged 22 to 35 yr, exhibiting early onset
      periodontitis. Thirty patients were smokers (30.9 cigarettes/d) and 30 non
      smokers. Smokers had a higher proportion of deep pockets (PD >5 mm), especially
      in the maxilla anterior and premolar regions (p < 0.001) and presented a
      significantly greater mean probing depth and attachment loss (p <0.05) in
      diseased sites and a significantly greater alveolar bone loss (p <0.01) compared
      to non-smokers. Two pooled bacterial samples were obtained from each patient.
      Samples were collected from the deepest periodontal pockets of each quadrant. The
      samples were cultured anaerobically and in 10% CO2 plus air for bacterial
      isolation using selective and non-selective media. Isolates were characterized to
      species level by conventional biochemical tests and various identification kits.
      Smokers harboured a greater number of bacteria in total. Analysis of bacterial
      counts using the ANOVA (Mann-Whitney U-test) showed that Staphylococcus aureus,
      Peptostreptococcus micros, Campylobacter concisus, Escherichia coli, Bacteroides
      forsythus, C. gracilis, C. rectus, Porphyromonas gingivalis, Selenomonas
      sputigena, Candida albicans and Aspergillus fumigatus were found in significantly
      higher numbers and more frequently in smokers while Streptococcus intermedius, A.
      naeslundii, A. israelii and Eubacterium lentum were detected more frequently and
      in significantly higher proportions in non-smokers. The isolation of bacteria
      belonging to the exogenous flora such as E. coli, C. albicans, A. fumigatus and
      S. aureus in smokers' microbiota underscores the importance of the host that is
      adversely affected by cigarette smoking.

PMID- 10086884
TI  - Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates
      production of interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and
      interleukin-1 receptor antagonist in human whole blood.
AB  - Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) is supposed to be
      an important etiological agent in localized juvenile periodontitis (LJP). We have
      studied the effect of lipopolysaccharide (LPS) extracted from these
      periodontopathogenic bacteria on synthesis of the proinflammatory cytokines,
      interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin
      6 (IL-6) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) in
      human whole blood. LPS from A. actinomycetemcomitans in concentrations > or =1
      ng/ml induced a significant production of all these proinflammatory cytokines,
      whereas LPS from Escherichia coli (E. coli), strain 026:B6 had to be added in
      concentrations > or =1 microg/ml to obtain a similar effect. Similarly, LPS from
      A. actinomycetemcomitans > or =0.1 ng/ml resulted in production of IL-1ra, while
      LPS from E. coli 026:B6 had to be added at > or =10 ng/ml to obtain similar
      effects. It has been suggested that the ratio between production of
      proinflammatory and anti-inflammatory cytokines may influence the outcome of
      periodontal diseases. Other in vitro and in vivo studies have, however, indicated
      that very large excesses (100-1000 times) of IL-1ra compared to IL-1beta are
      required to shift the IL-1ra:IL-1beta ratio in favor of an inhibition of IL-1
      bioactivity. In our ex vivo system, we found that stimulation with extremely low
      doses of A. actinomycetemcomitans LPS (0.1-1 ng/ml) resulted in IL-1ra production
      solely, without concomitant production of IL-1beta, the excess of IL-1ra over IL
      1beta peaking at 1 ng/ml, which accordingly should suggest that LPS from A.
      actinomycetemcomitans primarily has proinflammatory effects.

PMID- 10086885
TI  - Lectins inhibit periodontal ligament fibroblast attachment, spreading and
      migration on laminin substrates.
AB  - The ways in which carbohydrate signals from the extracellular matrix influence
      the responses of periodontal ligament (PDL) fibroblasts are essentially unknown.
      The purpose of this study, using video digital image analysis, was to examine the
      effects of lectins on the attachment, spreading and migrational responses of rat
      periodontal ligament fibroblasts on the highly glycosylated glycoprotein laminin
      (LN) in vitro. PDL fibroblasts were isolated from rat molar teeth and grown in
      culture. Bound LN and control substrates (bovine serum albumin and untreated
      plastic) were incubated with solutions of either wheatgerm agglutinin (WGA),
      specific for N-acetylglucosamine, or concanavalin A (ConA), specific for mannose,
      in 96-well plates. Unbound lectin was rinsed away and 10.0 x 10(3) cells were
      seeded per well and allowed to attach for 1.5 h. Incubation of LN substrates with
      WGA, prior to the addition of any cells, inhibited PDL fibroblast binding more
      than 5-fold. ConA, however, had no effect on cell binding but inhibited mean
      individual cell spreading nearly 3-fold under similar assay conditions. The
      effects could be prevented by adding each lectin's respective specific sugar. The
      lectins had no effects on the control substrates. In a 24-h cell migration assay
      WGA and ConA both significantly inhibited migration of PDL fibroblasts. It is
      likely that WGA inhibited cell attachment and cell migration, by binding to
      oligosaccharides and blocking access to adjacent polypeptide cell recognition
      sequences on LN. The results from the ConA experiments, where binding was allowed
      but spreading was severely inhibited, suggest a possible informational role for
      the carbohydrates present on LN.

PMID- 10086886
TI  - Effect of microbial siderophores on matrix metalloproteinase-2 activity.
AB  - Matrix metalloproteinases (MMPs) are capable of cleaving almost all
      macromolecules of the extracellular connective tissue matrix and are thought to
      play a major role in tissue destructive inflammatory diseases such as
      periodontitis. The aim of this study was to determine the effects of
      siderophores, which are iron-chelating molecules produced by a variety of
      microorganisms, on the activity of MMP-2. Heat-denatured type I collagen
      (gelatin) was incubated with p-aminophenylmercuric acetate-activated MMP-2 and
      siderophores. Degradation of gelatin was monitored by SDS-PAGE and Coomassie blue
      staining. Ferrichrome, rhodotorulic acid, desferoxamine mesylate and 2,3
      dihydroxybenzoic acid were found to inhibit the MMP-2 activity whereas beta
      phenylpyruvic acid had no effect. The inhibition could be reversed by adding an
      excess calcium chloride or ferric chloride to the assay mixtures. Our study
      suggests that microbial siderophores may represent new-potential therapeutic
      molecules for the treatment of destructive inflammatory diseases involving excess
      MMP-2 activity, such as periodontitis.

PMID- 10086887
TI  - Periodontal immune responses of human lymphocytes in Actinobacillus
      actinomycetemcomitans-inoculated NOD/SCID mice engrafted with peripheral blood
      leukocytes of periodontitis patients.

PMID- 10086888
TI  - Periodontal probing depths of adolescent sickle cell anaemic (SCA) Nigerians.

PMID- 10086889
TI  - Corticomotoneuronal PSTH studies.

PMID- 10086890
TI  - Assessment of upper and lower motor neurons in Kennedy's disease: implications
      for corticomotoneuronal PSTH studies.
AB  - We used peristimulus time histograms (PSTHs) to estimate characteristics of the
      composite excitatory postsynaptic potentials (EPSPs) generated at the anterior
      horn cell by a descending cortical volley induced by subthreshold transcranial
      magnetic stimuli in 11 normal subjects, 9 patients with DNA-confirmed Kennedy's
      disease, and 10 patients with amyotrophic lateral sclerosis (ALS). In Kennedy's
      disease the mean of the estimated EPSP amplitude (3.5 +/- 1.6 mV), as well as the
      means of duration (4.1 +/- 1.3 ms) and onset latency (20.4 +/- 2.7 ms) of the
      primary peak of 35 different motor units were not significantly different from
      normal subjects, in whom corresponding values of 49 motor units measured 2.9 +/-
      1.6 mV (EPSP amplitude), 3.5 +/- 1.4 ms (duration) and 19.3 +/- 2.8 ms (onset
      latency). In 48 motor units of patients with ALS the mean of the estimated EPSP
      amplitude, duration, and latency measured 2.7 +/- 1.8 mV, 7.8 +/- 5.7 ms, and
      24.0 +/- 6.5 ms, respectively, differing significantly from normal subjects and
      patients with Kennedy's disease. The normal cortically induced EPSP in Kennedy's
      disease is very different from the range of EPSP abnormalities in ALS, indicating
      that lower motor neuron disease per se does not result in an abnormal cortically
      induced EPSP derived from PSTHs. The normal findings in Kennedy's disease support
      our previous suggestions that the EPSP abnormalities in ALS are supraspinal in
      origin.

PMID- 10086891
TI  - Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic
      muscle.
AB  - We hypothesized that inactivity-induced remodeling of neuromuscular junctions
      (NMJs) depends on fiber type and the match between muscle fiber and motoneuron
      (MN) activities. Two inactivity models were studied in rat diaphragmatic muscle:
      spinal hemisection at C2 (SH), where both diaphragmatic muscle fibers and phrenic
      MNs were inactive, and tetrodotoxin (TTX) nerve blockade, where only muscle
      fibers were inactive. After 2 weeks of inactivity, there was increased number of
      pre- and postsynaptic branches (fragmentation) of NMJs at type IIx/b fibers in
      both models. In addition, planar NMJ areas at type IIx/b fibers in the SH model
      were enlarged. In contrast, NMJs at type I and IIa fibers were unaffected in both
      SH and TTX models. Functionally, neuromuscular transmission in diaphragmatic
      muscle fibers improved in the SH model, but worsened in the TTX model, compared
      to controls. These results suggest that NMJ remodeling depends on the level of MN
      activity. The relative preservation of NMJs at type I and IIa fibers suggests a
      potential for recovery from diaphragmatic paralysis in the clinical setting, at
      least for respiratory behaviors.

PMID- 10086892
TI  - The mixed nerve silent period is prolonged during a submaximal contraction
      sustained to failure.
AB  - The purpose of this study was to determine the effect of a sustained contraction
      of vastus lateralis on the silent period (SP) in the surface electromyogram (EMG)
      following direct neural stimulation. Five men and 5 women performed isometric
      knee extension at 30% maximal voluntary contraction (MVC) to the limit of
      endurance. During the contraction, EMG increased, and superimposed twitch
      amplitude and time to peak tension decreased, but the SP duration did not change.
      After 10 min of recovery, MVC had returned to its initial value, and the
      potentiated twitch amplitude was 70% of initial value, but the SP was now 11%
      shorter. Based on these results, we hypothesize that during a sustained
      contraction of 30% MVC, the increase in central drive may have been offset by
      inhibitory input from the periphery, but after 10 min of recovery the SP was
      shortened because of increased central drive. This aspect of the SP's behavior
      should be taken into account whenever it is employed as a diagnostic tool.

PMID- 10086893
TI  - Physiological and immunohistochemical characterization of cisplatin-induced
      neuropathy in mice.
AB  - We investigated the neuropathic effects of cisplatin in two groups of mice
      treated with 5 or 10 mg/kg/week of cisplatin for 7 or 8 weeks. Peripheral nerve
      functions were evaluated by sweat imprints, and electrophysiological, rotarod,
      and nociceptive tests. Protein gene product 9.5 (PGP), calcitonin gene-related
      peptide (CGRP), and vasoactive intestinal peptide (VIP) were
      immunohistochemically localized in footpads. Tibial nerves were analyzed
      morphometrically. Functional deficits developed progressively with higher
      cumulative doses, more markedly in mice treated with high than in those with low
      doses. From cumulative doses of 10 mg/kg, significant declines in sensory nerve
      conduction velocity and sudomotor responses were found, whereas motor and
      nociceptive functions were involved later. There were no morphometrical changes
      in tibial nerves. A marked decrease of CGRP- and VIP-immunoreactive nerves
      occurred in samples from treated mice, whereas PGP-labeled profiles decreased
      mildly at late stages. Impairment of the content of neuropeptides with
      neurosecretor role was detectable earlier than functional abnormalities.
      Immunohistochemical analysis of skin biopsies offers a useful diagnostic tool for
      peripheral neuropathies.

PMID- 10086894
TI  - Observations on the variability of the H reflex in human soleus.
AB  - H reflexes were evoked in human soleus by stimulating the tibial nerve at a
      constant intensity. Each trial was then assigned to one of three groups on the
      basis of the amplitude of its H reflex; all trials in each group were then full
      wave rectified and reaveraged. There was a strong positive relationship between
      the amplitude of the H reflex and the level of electromyographic activity in the
      muscle at the time of onset of the H reflex, which reflects the activity of the
      motoneuronal pool when the afferent volley arrived. Thus, much of the variability
      of the H reflex is due to small changes in the level of activation of the
      motoneuronal pool during repeated trials. The steady torque preceding the H
      reflex was a poor predictor of the H-reflex amplitude, presumably because of the
      delay between the changes in the electrical activity of motoneurons and the
      mechanical outcome thereof.

PMID- 10086895
TI  - Association of IGF-I and IGF-II with myofiber regeneration in vivo.
AB  - This study examined expression of insulinlike growth factor (IGF) in the
      myofibers and nonmyofibrillar structures of murine soleus muscle following
      contraction-induced damage. Identifying the cellular sources of this myogenic
      growth factor could improve muscle rehabilitation strategies. Immunohistochemical
      analysis of muscle sections indicated that the number of myofibers expressing
      both IGF-I and IGF-II increased significantly at 4, 7, and 10 days following
      injury, compared with control. Muscle spindles and vascular tissue expressed only
      IGF-II, and staining intensity did not change following injury. The number of
      fibers expressing developmental myosin heavy chain increased significantly at 7
      and 10 days postinjury, and these usually coexpressed IGF. No IGF-specific
      staining of interstitial/inflammatory cells was observed. Therefore, expression
      of IGF after mechanically induced fiber damage occurs exclusively within
      regenerating fibers without supplemental delivery of IGF to the tissue by
      inflammatory cells or changes in constitutive expression of IGF-II in vascular
      tissue.

PMID- 10086896
TI  - Electrophysiologic findings in amyloid myopathy.
AB  - Myopathy is an uncommon manifestation of systemic amyloidosis. A retrospective
      chart review of 17 patients seen between 1975 and 1997 with biopsy-proven amyloid
      myopathy was performed to characterize the electrophysiologic features. Nerve
      conduction study abnormalities occurred in 14 of 17 patients (82%). The most
      common abnormality was a low peroneal and/or tibial compound muscle action
      potential amplitude (n = 9). Mild abnormalities also occurred in seven other
      nerves. Repetitive stimulation at 2 Hz in 10 nerves was normal. Electromyography
      demonstrated fibrillation potentials in 69% of muscles, most frequently in the
      gluteus medius (90%) and paraspinals (87%). The fibrillation potentials were
      sparse in 60%. Short-duration, low-amplitude motor unit potentials (MUPs) were
      found in 72% of the muscles examined, were mild in 81%, and were more common in
      proximal muscles. Long-duration MUPs were found in 19% of muscles and a mixed
      population of MUPs in 4%. These findings are similar to those of common chronic,
      inflammatory myopathies.

PMID- 10086897
TI  - A skin blister method to study epidermal nerves in peripheral nerve disease.
AB  - Skin is a reservoir of sensory and autonomic nerve fibers that are potential
      indicators of peripheral nerve disease. Biopsies of skin have shown that sensory
      nerves in the most superficial layer of skin, the epidermal nerve fibers (ENFs),
      are reduced in patients with polyneuropathy. This report describes a minimally
      invasive skin blister method to isolate, image, and obtain quantitative analysis
      of ENFs. Blisters are made by applying a suction capsule to skin. The epidermal
      roof of the blister is excised, immunostained, whole mounted, and analyzed for
      ENF number and distribution. A reduction in number and abnormal distribution of
      ENFs are early indicators of peripheral nerve disease. Illustrations of skin
      blister and skin biopsy specimens from patients with different types of
      peripheral nerve disorders are included. These patients were chosen because their
      findings demonstrate the complementary information obtained by the blister and
      biopsy methods and the potential of the blister procedure to evaluate single
      nerve lesions and polyneuropathy and to follow the progress of ENF degeneration
      and regeneration.

PMID- 10086898
TI  - Motor nerve conduction velocity in very preterm infants.
AB  - Sufficient reference values for motor nerve conduction velocity (MNCV) in very
      preterm infants are not yet available. In the placebo infants within an L
      thyroxine supplementation trial, born at less than 30 weeks' gestation, ulnar and
      posterior tibial MNCV measurements were performed shortly after birth. Repeated
      measurements were done at 2 weeks, at term, and at 6 months corrected age. Cross
      sectional MNCV values obtained in 50 infants and longitudinal MNCV values
      obtained in 15 infants were analyzed in relation to postmenstrual age (PMA). Mean
      ulnar MNCV increased from 13 to 44 m/s and mean tibial MNCV from 11 to 37 m/s.
      Motor nerve conduction velocity was clearly related to PMA. Longitudinal MNCV
      values were consistent with cross-sectional MNCV values. Possible confounding
      factors did not have any significant effect on MNCV. In the ulnar nerve,
      extrauterine maturation during the first 2 weeks of life was delayed compared
      with intrauterine maturation.

PMID- 10086899
TI  - CMAP amplitude cartography of muscles innervated by the median, ulnar, peroneal,
      and tibial nerves.
AB  - The spatial and temporal distribution of compound muscle action potential (CMAP)
      amplitudes was mapped using 1 x 1-cm grids over thenar, hypothenar, dorsal foot,
      and foot sole muscles (seven maps each). The high-amplitude zone (HAZ, area where
      amplitudes were over 80% of the maximum amplitude) denoted susceptibility to
      changes in recording site. Thenar maps had one peak (spatially and temporally)
      with a HAZ of 3.5 +/- 2.3 cm2. Hypothenar maps had two peaks (spatially and
      temporally) with a HAZ of 7.7 +/- 3.6 cm2. Dorsal foot maps had one temporal
      peak, which could be split up spatially; the HAZ was smallest, at 1.7 +/- 1.7
      cm2. Foot sole muscles had one peak (spatially and temporally), with the largest
      HAZ at 18.4 +/- 6.1 cm2. Wave-form differences were ascribed to differences in
      muscle anatomy, architecture, and variability. These explain differences in
      amplitude reproducibility between nerves and the differing effect that increasing
      electrode size has on reproducibility.

PMID- 10086900
TI  - Induction of heat-shock protein 72 in rat skeletal muscle does not increase
      tolerance to ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury is implicated in the failure of free flap and replant
      surgeries and is associated with the pathogenesis of a wide variety of clinical
      diseases including stroke, myocardial infarction, spinal injury, and compartment
      syndromes. We used a skeletal muscle flap model to test if the induction of heat
      shock protein 72 (HSP72) by mild hyperthermia provides tolerance against ischemia
      reperfusion injury. Immunocytochemistry and Western blot analysis verified
      increased production of HSP72 in the gracilis muscle of globally heated rats.
      Neutrophil accumulation in the microvasculature and postischemic muscle survival
      after ischemia-reperfusion were unaltered by preischemic hyperthermia, indicating
      HSP72 induction is not sufficient to provide resistance against severe injury in
      skeletal muscle.

PMID- 10086901
TI  - Multiple A waves in Guillain-Barre syndrome.
AB  - In 13 of 14 patients with Guillain-Barre syndrome (GBS), we observed multiple A
      waves in at least one limb nerve on routine electroneurographic studies within 7
      days after onset of symptoms. The patient without A waves had a severe axonal
      type of GBS with tetraplegia and almost complete loss of M responses following
      electrical stimulation of limb nerves. In the remaining 13 patients, on average 8
      +/- 2 (mean +/- SD) A waves were present in each tibial nerve (n = 24) and 4 +/-
      1 A waves in each peroneal nerve (n = 26). About half of the A waves were below
      50 microV in amplitude, whereas amplitudes were higher than 120 microV in only 22
      of 299 A waves. Of these A waves, 68 were not constantly elicitable. There was a
      significant correlation between the number of A waves up to 50 ms poststimulus
      and the reduction in amplitude of the compound muscle action potential when
      elicited with proximal compared to distal stimulation in the peroneal (n = 26, P
      < 0.0005; Kendall's tau) and tibial nerves (n = 24, P < 0.002). Therefore, in GBS
      both conduction block and A waves are presumably signs of inflammatory nerve
      lesions. The existence of multiple A waves soon after onset of symptoms seems to
      be a sensitive sign of GBS.

PMID- 10086902
TI  - Standardization of anal sphincter EMG: technique of needle examination.
AB  - The external anal sphincter (EAS) anatomy is complex, and no exact technique of
      needle electrode insertion into it for electromyography (EMG) has been described.
      To define optimal positions for needle electrode insertions, EAS muscle
      topography was studied by concentric needle EMG. Fifteen women without
      uroneurological disorders were examined. Perpendicular insertions were made
      superficially (just under the mucosa) at the mucocutaneous junction, 5 and 10 mm
      more proximally (toward the anus), and at the anal orifice. In addition, at the
      anal orifice, deeper insertions were made. Superficially, EMG activity was
      detected at the mucocutaneous junction in 9 (60%) subjects. In the remaining 6,
      the muscle was found either 5 mm (in 5) or 10 mm (in 1) more centrally. At the
      anal orifice, superficial EMG activity was present in 67% of women. On deep
      insertion (15-25 mm) at the anal orifice, muscle was always present. It is
      suggested that, in further studies, the portions of the EAS muscle examined
      should be specified.

PMID- 10086903
TI  - Multisystem neuronal involvement and sicca complex: broadening the spectrum of
      complications.
AB  - We report two patients with multisystem neuronal involvement associated with
      sicca complex. One had a lower motor neuron syndrome combined with a flaccid
      bladder and rectum. The second patient had unilateral hearing loss, sensory
      neuronopathy, Adie's pupils, upper motor neuron signs, and autopsy-proven
      anterior horn cell degeneration. Our cases lead us to propose that the spectrum
      of neuronal involvement occurring with sicca syndrome may be wider than is
      currently appreciated.

PMID- 10086904
TI  - Practice parameter for electrodiagnostic studies in ulnar neuropathy at the
      elbow: summary statement. American Association of Electrodiagnostic Medicine,
      American Academy of Neurology, American Academy of Physical Medicine and
      Rehabilitation.

PMID- 10086905
TI  - AAEM case report 33: costoclavicular mass syndrome. American Association of
      Electrodiagnostic Medicine.
AB  - A true costoclavicular mass syndrome associated with a brachial plexopathy is
      rare. We report the occurrence of a severe brachial plexopathy as a late
      complication of a displaced midclavicular fracture. An exuberant callus
      associated with the clavicular fracture acted as a mass lesion to compress the
      brachial plexus within the costoclavicular space (i.e., between the clavicle and
      the first rib). The clinical features and the electrodiagnostic findings in this
      patient were crucial in suggesting the diagnosis, which was subsequently
      confirmed by radiographic studies and surgical exploration. Surgical excision of
      the hyperabundant callus and freeing of the entrapped brachial plexus resulted in
      marked improvement of the patient's neurological symptoms. Recognition of this
      uncommon complication of a clavicular fracture is important for the timely
      diagnosis of this treatable problem.

PMID- 10086906
TI  - Critical illness polyneuropathy.

PMID- 10086907
TI  - Focal conduction block in n-hexane polyneuropathy.

PMID- 10086908
TI  - F waves.

PMID- 10086909
TI  - The electromyogram in obstetric brachial palsy is too optimistic: fiber size or
      another explanation?

PMID- 10086910
TI  - Effects of a low-dose L-carnitine supplement on an adult patient with
      mitochondrial trifunctional protein deficiency.

PMID- 10086911
TI  - Muscular necrotizing vasculitis as the initial manifestation of Behcet's disease.

PMID- 10086912
TI  - As You Like It, Part 2: A critique and historical review of the electron
      microscopy literature.
AB  - As You Like It, Part 2, is a continuation of the lecture given at UltraPath VIII
      in 1996. It is meant to be a critical historical review of some topics of
      interest to electron microscopists that will show what went wrong and perhaps
      also why. Topics are presented under the following headings : (1) Amianthoid
      Fibers and Giant Collagen Fibrils, (2) Ribosome-Lamella Complex, (3) Globular
      Filamentous Bodies, and (4) Siderosomes, Hemosiderin vs. Ferritin.

PMID- 10086913
TI  - Comparative ultrastructural studies on mitochondrial pathology in the liver of
      AIDS patients: clusters of mitochondria, protuberances, "minimitochondria,"
      vacuoles, and virus-like particles.
AB  - The present comparative conventional electron microscopic studies of the liver
      biopsy in 20 AIDS patients revealed numerous disintegrated mitochondria in
      hepatocytes, Kupffer cells lymphocytes, and eosinophile leukocytes. It was
      observed that (1) AIDS mitochondria are clustered, disorganized, and with
      protuberances; (2) the number of cristae is reduced and they are branched
      dichotomously; (3) vacuoles are located both within the mitochondria and, in
      their vicinity, (4) " minimitochondria" are within the ordinary mitochondria; (5)
      virus-like particles are at the periphery of electron-dense mitochondrial
      remains.

PMID- 10086914
TI  - Immunohistochemical and ultrastructural study of microvessels in diabetic veins.
AB  - The aim of this study was to examine the localization and features of the
      intramural microvessels in the wall of inferior limb veins in diabetic patients.
      The study was conducted in a group of 10 insulin-dependent diabetic patients, who
      had suffered inferior limb amputation as a consequence of chronic limb ischemia.
      Sections of long saphenous and posterior tibial veins were investigated by light
      and transmission electron microscope. The von Willebrand factor and albumin were
      detected by immunohistochemical techniques. The results show the presence of
      numerous microvessels in the intima and inner third of the media layer of the
      venous wall of the sections studied. These microvessels present morphological and
      functional modifications in relation to those observed in the control veins. They
      also showed the presence of endothelial cells migrating from the lumen. The
      authors conclude that the venous wall of inferior limbs in amputated diabetic
      patients presents a neovascularization process. Some of the endothelial cells of
      the venous lumen can also have a role in the angiogenesis.

PMID- 10086915
TI  - Granuloma annulare: an elastic tissue disease? Case report and literature review.
AB  - Granuloma annulare (GA) is a condition characterized by the presence of
      palisading granulomas usually in the dermis. Traditionally, the histopathological
      changes are described as consisting of focal degeneration of dermal collagen
      fibers. However, no convincing evidence for such alteration is found in the
      literature. A histopathological study was done to ascertain the nature of the
      dermal abnormality. Ten skin biopsies showing lesions of GA were studied by light
      and electron microscopy. On light microscopy, all lesions showed focal dermal
      degeneration with near total loss of elastic fibers. Ultrastructural examination
      in nine cases demonstrated degenerated elastic fibers with loss of peripheral
      microfibrils and abnormal elastic matrix. The degenerated elastic fibers were
      surrounded by intact collagen fibers. These findings show that the main
      alteration in GA is elastic fiber degeneration and strongly suggest that the
      primary target leading to the development of this disorder is injury to the
      elastic tissue.

PMID- 10086916
TI  - Wilson's disease coexisting with viral hepatitis type C: a case report with
      histological and ultrastructural studies of the liver.
AB  - Histopathological and ultrastructural findings in the liver of a female patient
      who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are
      reported. Light and electron microscopy examinations demonstrated a variety of
      morphological alterations--many of them frequently seen in livers of patients
      with WD and others that can be found in cases presenting HCV infection. The
      influence of coexistence of these two diseases on morphological changes is
      discussed.

PMID- 10086917
TI  - Signet ring epithelioid stromal tumor of the small intestine.
AB  - Cells having a signet ring appearance can occur in mesenchymal, lymphoid, and
      other nonepithelial neoplasms. We report the case of an intestinal stromal tumor
      with smooth muscle differentiation and a prominent signet ring cell component.
      The presence of signet ring forms of smooth muscle cells in sections of paraffin
      embedded tissue often contrasts with a lack of cytoplasmic spaces by electron
      microscopy, and the ultrastructural finding of signet ring-like areas in the
      present case can be attributed to the fact that the tissue for electron
      microscopy was retrieved from paraffin blocks where this peculiar artifact
      already existed. Ultrastructural examination of the signet ring-like areas
      suggests that they originated as retraction spaces which may have resulted from
      variations in intracellular tension forces related to the distribution of actin
      filaments.

PMID- 10086918
TI  - Clear cell meningioma of the lumbo-sacral spine with chordoid features.
AB  - Clear cell meningioma (CCM) is a peculiar variant that differs from conventional
      meningioma in affecting younger patients, arising more often in spinal or
      cerebellopontine locations, and showing a higher recurrence rate. Classical
      meningothelial areas are scarce in these tumors and the differential diagnosis
      with other neoplasms, particularly metastatic carcinoma, is often difficult. We
      report a case of clear cell meningioma from the lumbosacral spine in which
      location, radiologic presentation, light microscopic appearance in initial
      sampling, and some of the ultrastructural findings were reminiscent of chordoma.
      The tumor cells were diffusely positive for vimentin and very focally positive
      for epithelial membrane antigen. Ultrastructural demonstration of interdigitating
      cell processes joined by numerous desmosomes confirmed the diagnosis of CCM.

PMID- 10086919
TI  - Fibrous long-spacing collagen in Kaposi's sarcoma.

PMID- 10086920
TI  - A global view of oral diseases: today and tomorrow.

PMID- 10086921
TI  - Caries conditions among 2-5-year-old immigrant Latino children related to
      parents' oral health knowledge, opinions and practices.
AB  - OBJECTIVES: To collect baseline data prior to initiating a community-based, oral
      health promotion program in an inner city Latino community in Washington DC,
      populated by Central American immigrants. METHODS: In 1995, an oral survey of a
      convenience sample of children 2-5 years of age (n = 142) and a survey of the
      knowledge, opinions and practices (KOP) of their parents (n = 121) were
      completed. Clinical data of children were matched with parent respondents of the
      KOP survey. Data were analyzed for statistical associations using univariate odds
      ratios, Fisher's exact tests, and multiple logistic regression. RESULTS: Only 53%
      of the children were caries free. Eighteen percent of all children were in need
      of immediate dental care and 26% were in need of early or non-urgent dental care.
      Only 7% of the parents knew the purpose of sealants and 52% knew the purpose of
      fluorides. Further, only 9% thought that brushing with toothpaste can prevent
      tooth decay The strongest predictors of dental caries in this population, after
      adjusting for child's age and mother's education, were recency of mother's
      residence in the United States and report of an uncooperative child when
      attempting toothbrushing. CONCLUSIONS: Regimens of caries prevention have been
      successful in reducing dental decay for a large segment of the US population, yet
      this disease remains prevalent especially among low socioeconomic groups. The
      oral health status of the children and the oral health KOP of the parents in this
      community are disturbingly deficient.

PMID- 10086922
TI  - Cigarette smoking and periodontitis: methodology to assess the strength of
      evidence in support of a causal association.
AB  - Identification of the cause of the development and progression of periodontitis
      has received extensive attention, with notable advances over the past decade in
      clinical, microbiological, immunological, biochemical, and behavioral knowledge.
      However, it is still largely unknown which factors lead to the conversion of non
      destructive forms of periodontal disease into destructive forms and disease
      progression. Chronic adult periodontitis is believed to be influenced by an
      interaction of host defense and environmental factors. Although these variables
      have been studied extensively, no study has employed randomized controlled
      prospective human or randomized controlled community intervention designs,
      methodologies necessary to prove a variable to be a cause of periodontitis. Owing
      to the absence of literature employing rigorous experimental design, this article
      assesses systematically observational, cross-sectional and longitudinal studies
      to examine the potential causal association between cigarette smoking and
      periodontitis. The methodology of Sir Bradford Hill's criteria for causation was
      used as the framework. Results suggest that cigarette smoking is causally
      associated with periodontitis. That is, cigarette smoking is consistently
      associated with an increased prevalence/severity of periodontitis and is
      suspected on theoretical grounds of playing a causal role. Hill's criteria
      provide a useful methodology to better understand the pathogenesis of periodontal
      diseases and may be applied to study the pathogenesis of other dental diseases as
      well.

PMID- 10086923
TI  - Appropriate use of fluoride supplements for the prevention of dental caries.
      Consensus Conference of the Canadian Dental Association. Toronto, Canada, 28-29
      November 1997. Introduction.

PMID- 10086924
TI  - Prevention and reversal of dental caries: role of low level fluoride.
AB  - Dental caries is a bacterially based disease that progresses when acid produced
      by bacterial action on dietary fermentable carbohydrates diffuses into the tooth
      and dissolves the mineral, that is, demineralization. Pathological factors
      including acidogenic bacteria (mutans streptococci and lactobacilli), salivary
      dysfunction, and dietary carbohydrates are related to caries progression.
      Protective factors which include salivary calcium, phosphate and proteins,
      salivary flow, and fluoride in saliva can balance, prevent or reverse dental
      caries. Fluoride works primarily via topical mechanisms which include (1)
      inhibition of demineralization at the crystal surfaces inside the tooth, (2)
      enhancement of remineralization at the crystal surfaces (the resulting
      remineralized layer is very resistant to acid attack), and (3) inhibition of
      bacterial enzymes. Fluoride in drinking water and in fluoride-containing products
      reduces tooth decay via these mechanisms. Low but slightly elevated levels of
      fluoride in saliva and plaque provided from these sources help prevent and
      reverse caries by inhibiting demineralization and enhancing remineralization. The
      level of fluoride incorporated into dental mineral by systemic ingestion is
      insufficient to play a significant role in caries prevention. The effect of
      systemically ingested fluoride on caries is minimal. Fluoride "supplements" can
      be best used as a topical delivery system by sucking or chewing tablets or
      lozenges prior to ingestion.

PMID- 10086925
TI  - Biological mechanisms of dental fluorosis relevant to the use of fluoride
      supplements.
AB  - Fluorosis occurs when fluoride interacts with mineralizing tissues, causing
      alterations in the mineralization process. In dental enamel, fluorosis causes
      subsurface hypomineralizations or porosity, which extend toward the dentinal
      enamel junction as severity increases. This subsurface porosity is most likely
      caused by a delay in the hydrolysis and removal of enamel proteins, particularly
      amelogenins, as the enamel matures. This delay could be due to the direct effect
      of fluoride on the ameloblasts or to an interaction of fluoride with the proteins
      or proteinases in the mineralizing matrix. The specific mechanisms by which
      fluoride causes the changes leading to enamel fluorosis are not well defined;
      though the early-maturation stage of enamel formation appears to be particularly
      sensitive to fluoride exposure. The development of fluorosis is highly dependent
      on the dose, duration, and timing of fluoride exposure. The risk of enamel
      fluorosis is lowest when exposure takes place only during the secretory stage,
      but highest when exposure occurs in both secretory and maturation stages. The
      incidence of dental fluorosis is best correlated with the total cumulative
      fluoride exposure to the developing dentition. Fluoride supplements can
      contribute to the total fluoride exposure of children, and if the total fluoride
      exposure to the developing teeth is excessive, fluorosis will result.

PMID- 10086926
TI  - Fluoride supplements and fluorosis: a meta-analysis.
AB  - This paper presents a systematic review of the dental literature that was carried
      out to investigate whether the regular use of fluoride supplements in non
      fluoridated communities during the period of tooth development increases the risk
      of dental fluorosis. A MEDLINE search was organized for all documents published,
      in English, between January 1966 and September 1997 using the following key
      words: fluorosis, dental, fluoride, fluoride supplement or supplements, drop or
      drops, and tablet or tablets. Twenty-four studies that assessed the development
      of dental fluorosis in children who had used fluoride supplements earlier in
      their life were included in this review. Of the 24 studies, 10 were cross
      sectional/case control studies and four were follow-up studies. These studies had
      data that allowed a quantitative estimation of the risk of developing dental
      fluorosis in users of fluoride supplements. The other 10 studies were excluded
      because they either did not present enough data or had other methodological
      problems. A qualitative review of the studies found a consistent and strong
      association between the use of fluoride supplements and dental fluorosis. The
      meta-analyses of the cross-sectional/case-control studies estimated that the odds
      ratio of dental fluorosis in users of fluoride supplements compared with non
      users ranged between 2.4 and 2.6. The meta-analyses of the follow-up studies
      estimated that the relative risk in long-term users was between 5.5 and 12.2.
      This review confirmed that in non-fluoridated communities the use of fluoride
      supplements during the first 6 years of life is associated with a significant
      increase in the risk of developing dental fluorosis.

PMID- 10086927
TI  - International fluoride supplement recommendations.
AB  - A telefax survey was conducted to determine the current and past recommended
      schedules for fluoride supplementation using tablets, salt or milk. Twenty-one of
      90 countries listed in the 1997 FDI directory responded. Information on
      additional countries was gathered from a recent textbook on fluoride and a dental
      health survey report. The summary table provided is far from comprehensive but it
      represents the best data available at this time. The conclusions are limited to
      the information received but there is a clear trend to lower dosage
      recommendations and no fluoride supplementation to very young children. Several
      issues are identified which should be addressed whenever fluoride tablet
      supplementation schedules are being considered.

PMID- 10086928
TI  - A re-examination of the pre-eruptive and post-eruptive mechanism of the anti
      caries effects of fluoride: is there any anti-caries benefit from swallowing
      fluoride?
AB  - The belief that fluoridated water reduces caries incidence by half stems from
      years of fluoridation studies where the caries rates of people in various
      fluoridated and non-fluoridated communities were compared. By their nature, the
      water fluoridation trials were not able to distinguish between the topical
      effects of the fluoride in the water and the systemic effects of the fluoride
      that is inevitably swallowed and incorporated into developing teeth. Some
      attempts have been made to estimate the contribution of systemic fluoride to the
      control of dental caries but researchers are discovering that the topical effects
      of fluoride are likely to mask any benefits that ingesting fluoride might have.
      In this updated review of the pre-eruptive vs. post-eruptive benefits of fluoride
      in the prevention of dental caries, a re-examination of the literature, which is
      often cited to support the notion that swallowing fluoride, either in water or in
      pill form, was done in recognition of the mounting evidence for the topical
      mechanism as being the primary mechanism for the prevention of dental caries.
      Maximum benefits from exposing newly erupted teeth to topical fluoride in the
      oral cavity may have been seriously under-estimated. This has obvious
      implications for the use of systemic fluorides to prevent dental caries and
      forces everyone working in the field to examine more closely the risks and
      benefits of fluoride in all its delivery forms.

PMID- 10086929
TI  - Fluoride supplements for young children: an analysis of the literature focusing
      on benefits and risks.
AB  - The use of fluoride supplements to prevent caries has been advised for more than
      100 years, but serious promotion of this strategy occurred only after the
      effectiveness of water fluoridation was established, in the late 1950s and 1960s.
      Although the effectiveness of fluoride supplements was apparently endorsed by
      many small clinical studies, closer examination of the experimental conditions of
      these, their methods and the analysis of their results undermined confidence in
      their findings. It is likely that confounding resulted in spurious conclusions in
      many of them. More modern, well-conducted clinical trials of supplements suggest
      that today, in children also exposed to fluoride from other sources such as
      toothpaste, the marginal effect of fluoride supplements is very small. There is
      evidence that fluoride lozenges, designed to maximise any local effect, may have
      a small caries preventive effect, particularly in deciduous teeth. Overall, poor
      compliance makes fluoride supplements a poor public health measure. Supplement
      use by young children is associated with a substantial risk of dental fluorosis.
      Fluorosis is an issue about which the public is becoming concerned in several
      countries and this concern, if translated into opposition to all fluoride use,
      could jeopardise the most successful caries preventive aid we have. The potential
      for dental fluorosis, concern about the public's reaction to this, the poor
      effectiveness of supplements and the public's poor compliance with their use are
      persuasive arguments for a radical reduction in the use of supplements by young
      children. Recent changes in fluoride dosage schedules and deferment of the age of
      commencing the use of supplements, implemented in many countries, have followed
      from these concerns. Supplements formulated as lozenges maximise topical exposure
      of enamel to fluoride and such products may offer older children and some adults
      a way of maintaining an elevated fluoride level in saliva at times when
      toothbrushing is not practical.

PMID- 10086930
TI  - Early growth and cardiovascular disease.

PMID- 10086931
TI  - Evidence for using nebulised antibiotics in cystic fibrosis.

PMID- 10086932
TI  - Is prolonged rotavirus infection a common cause of protracted diarrhoea?

PMID- 10086933
TI  - Survival after acute lymphocytic leukaemia: effects of socioeconomic status and
      geographic region.
AB  - National cancer registry data, linked to an areal measure of material
      deprivation, were used to explore possible socioeconomic and regional variation
      in the survival of children (0-14 years) diagnosed with acute lymphocytic
      leukaemia (ALL) in England and Wales from 1971 to 1990. Survival analysis and
      Poisson regression were used to estimate observed (crude) survival probabilities
      and the adjusted hazard of death. There was little evidence of a socioeconomic
      gradient in survival. Regional differences in survival were observed over time.
      These differences were most pronounced in the first six months after diagnosis,
      and may be attributable to differential access to centralised paediatric oncology
      services or treatment protocols, or to the artefact of variations in regional
      cancer registry practice. Similar analyses should be repeated for other, less
      treatable childhood cancers. The results of this study can be used to help
      identify ways of reducing regional variation in survival.

PMID- 10086934
TI  - Attentional ability among survivors of leukaemia.
AB  - Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19
      sibling controls was assessed using a neuropsychological model of attention.
      Analysis revealed that children who had received treatment for leukaemia
      exhibited significantly poorer performance on measures of the "focus encode" and
      "focus execute" elements of attention and on measures of the ability to respond
      to external cues and feedback. No significant differences in performance were
      found for measures of sustained attention and the ability to shift attention.
      These results indicate that children who have received treatment for leukaemia
      may experience highly specific attentional deficits that could have an impact on
      academic performance, particularly mathematical and reading skills. It is
      suggested that this underlying attentional deficit might be the source of the
      neuropsychological sequelae associated with the disease. Future attempts at
      remediation should incorporate activities specifically designed to ameliorate
      focusing difficulties.

PMID- 10086935
TI  - Ethology and cortical visual impairment 

PMID- 10086936
TI  - Assessment of the gonadotrophin-gonadal axis in androgen insensitivity syndrome.
AB  - OBJECTIVE: To study the value of measuring serum luteinising hormone (LH),
      follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT)
      in androgen insensitivity syndrome (AIS). DESIGN: Retrospective study of patients
      on a nationwide register of AIS. PATIENTS: Sixty one cases of AIS with androgen
      receptor (AR) dysfunction (abnormalities of the AR gene and/or abnormal AR
      binding) were divided into three age groups: infants, < 1 year old; children, 1
      13 years old; and postpubertal, > 13 years old. MEASUREMENTS: Age, dose of human
      chorionic gonadotrophin (hCG) stimulation, pre-hCG and post-hCG serum
      testosterone values, serum DHT values, and serum LH and FSH values before and
      after LH releasing hormone (LHRH) stimulation. RESULTS: In 23 of 30 infants
      testosterone was within age related reference ranges; six were above this range.
      The median testosterone rise following variable dosage of hCG was 9.5 times the
      basal value. The increment was not related to the hCG dose, age, or basal
      concentration of testosterone. The median basal and stimulated testosterone:DHT
      ratios were 2.5 and 6.1, respectively. The median increment in DHT was 2.2-fold.
      Seventeen of 18 FSH and 11 of 19 LH measurements were within age related ranges
      in infants; in seven patients LH values were above the range. LHRH stimulation
      performed in 39 patients showed an exaggerated LH in all age groups. The FSH
      response was not exaggerated in children. CONCLUSION: Although a positive hCG
      test excludes biosynthetic defects of testosterone, an inadequate response does
      not exclude AIS. Basal LH and testosterone may not be raised during early
      infancy. An LHRH stimulation test might be useful for evaluating cases of
      suspected AIS presenting in mid-childhood.

PMID- 10086937
TI  - Tests of adrenal insufficiency.
AB  - AIM: In suspected adrenal insufficiency, the ideal test for assessing the
      hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were
      compared in patients presenting with symptoms suggestive of adrenal
      insufficiency. METHOD: Responses to the standard short Synacthen test (SSST), the
      low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration
      were measured in 32 patients. A normal response to the synacthen test was defined
      as a peak serum cortisol of >/= 500 nmol/l and/or incremental concentration of
      >/= 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol
      concentration compared with other tests was calculated. RESULTS: Three patients
      had neither an adequate peak nor increment after the SSST and LDST. All had a
      serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had
      abnormal responses by both criteria to the LDST but had normal responses to the
      SSST. Three reported amelioration of their symptoms on hydrocortisone
      replacement. Twenty one patients had a normal response to both tests (of these,
      14 achieved adequate peak and increment after both tests and seven did not have
      an adequate peak after the LDST but had a normal increment). The lowest 08:00
      hour serum cortisol concentration above which patients achieved normal responses
      to both the LDST and SSST was 500 nmol/l. At this cut off value (compared with
      the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100%
      but specificity was only 33%. CONCLUSION: The LDST revealed mild degrees of
      adrenal insufficiency not detected by the SSST. The value of a single 08:00 hour
      serum cortisol concentration is limited.

PMID- 10086938
TI  - Growth hormone treatment in young children with Down's syndrome: effects on
      growth and psychomotor development.
AB  - BACKGROUND: Learning disability and short stature are cardinal signs of Down's
      syndrome. Insulin-like growth factor I (IGF-I), regulated by growth hormone (GH)
      from about 6 months of age, may be involved in brain development. AIMS: To study
      long term effects of GH on linear growth and psychomotor development in young
      children with Down's syndrome. Study design-Fifteen children with Down's syndrome
      were treated with GH for three years from the age of 6 to 9 months (mean, 7.4).
      Linear growth, psychomotor development, skeletal maturation, serum concentrations
      of IGF-I and its binding proteins (BPs), and cerebrospinal fluid (CSF)
      concentrations of IGF-II were studied. RESULTS: The mean height of the study
      group increased from -1.8 to -0.8 SDS (Swedish standard) during treatment,
      whereas that of a Down's syndrome control group fell from -1.7 to -2.2 SDS.
      Growth velocity declined after treatment stopped. Head growth did not accelerate
      during treatment. No significant difference in mental or gross motor development
      was found. The low concentrations of serum IGF-I and IGFBP-3 became normal during
      GH treatment. CONCLUSIONS: GH treatment results in normal growth velocity in
      Down's syndrome but does not affect head circumference or mental or gross motor
      development. Growth velocity declines after treatment stops.

PMID- 10086939
TI  - Growth in Sotos syndrome.
AB  - Although there are several reports on infant and childhood growth in patients
      with Sotos syndrome, there is little information on the final height achieved and
      puberty. Growth data on 40 patients (20 female and 20 male) aged 2-31 years were
      collected. These showed that patients with Sotos syndrome are excessively tall at
      birth, during infancy, and during childhood. Disproportionately long limbs
      constitute much of the increase in stature. However, the combination of advanced
      bone age and early onset of menarche led to a mean (SD) final height of 172.9
      (5.7) cm in women. This is within the normal range for the population. Most of
      the men also attained a final height (mean, 184.3 cm; SD, 6.0) within the normal
      range, although exceptions were more likely in men than in women. Therefore,
      these results show that most patients with Sotos syndrome do not require
      intervention to limit their adult height.

PMID- 10086940
TI  - Lorenzo's oil: the sequel 

PMID- 10086941
TI  - Randomised controlled trial of budesonide for the prevention of post
      bronchiolitis wheezing.
AB  - BACKGROUND: Previous studies suggest that recurrent episodes of coughing and
      wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To
      assess the efficacy of budesonide given by means of a metered dose inhaler,
      spacer, and face mask in reducing the incidence of coughing and wheezing episodes
      up to 12 months after acute viral bronchiolitis. METHODS: Children under the age
      of 12 months admitted to hospital with acute viral bronchiolitis were randomised
      to receive either budesonide or placebo (200 microg or one puff twice daily) for
      the next eight weeks. Parents kept a diary card record of all episodes of
      coughing and wheezing over the next 12 months. RESULTS: Full follow up data were
      collected for 49 infants. There were no significant differences between the two
      study groups for the number of infants with symptom episodes up to six months
      after hospital discharge. At 12 months, 21 infants in the budesonide group had
      symptom episodes compared with 12 of 24 in the placebo group. The median number
      of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1
      (range, 0-11) in those who received placebo. Because there is no pharmacological
      explanation for these results, they are likely to be caused by a type 1 error,
      possibly exacerbated by there being more boys in the treatment group. CONCLUSION:
      Routine administration of budesonide by means of a metered dose inhaler, spacer,
      and face mask system immediately after acute viral bronchiolitis cannot be
      recommended.

PMID- 10086942
TI  - Improvement of nebulised antibiotic delivery in cystic fibrosis.
AB  - AIM: To investigate deposition patterns and to assess the delivery rate of two
      nebuliser systems in children with cystic fibrosis (CF). METHODS: Thirty three
      children with CF on regular treatment with nebulised antibiotics had radioisotope
      scans performed using technetium-99m labelled aerosol antibiotic generated by a
      Ventstream nebuliser (median mass diameter (MMD), 3.3 microm; delivery rate, 0.
      075 ml/min) under conditions similar to their routine home practice. The
      inhomogeneity of the images was scored on a 1-10 rating scale (a low score
      indicating even distribution of the antibiotic), and stomach deposition was
      measured as a percentage of overall deposition. Twenty patients had a repeat scan
      using an Optimist nebuliser (MMD, 1.8 microm; delivery rate, 0.02 ml/min).
      RESULTS: The mean inhomogeneity scores were 5.4 in the Ventstream group and 3. 5
      in the Optimist group. Mean stomach deposition was 17.3% in the 33 patients using
      the Ventstream nebuliser. There was an inverse relation between height and
      stomach deposition (r = 0.69). In the 20 patients who had both nebulisers, the
      mean percentages of stomach deposition for the Ventstream and Optimist nebulisers
      were 11.8% and 1.6%, respectively. The Ventstream nebuliser delivered antibiotic
      at an average 2.8 times faster rate than the Optimist nebuliser. IMPLICATIONS: A
      smaller particle size results in a more homogenous distribution of the antibiotic
      in the lungs with decreased stomach deposition. This should not be seen as a
      recommendation to use the Optimist nebuliser because more antibiotic was
      delivered to most parts of the lung with the Ventstream because of its increased
      delivery rate.

PMID- 10086943
TI  - Rheumatic chorea in northern Australia: a clinical and epidemiological study.
AB  - To describe the epidemiology and clinical features of Sydenham's chorea in the
      Aboriginal population of northern Australia a review was conducted of 158
      episodes in 108 people: 106 were Aborigines, 79 were female, and the mean age was
      10.9 years at first episode. Chorea occurred in 28% of cases of acute rheumatic
      fever, carditis occurred in 25% of episodes of chorea, and arthritis in 8%.
      Patients with carditis or arthritis tended to have raised acute phase reactants
      and streptococcal serology. Two episodes lasted at least 30 months. Mean time to
      first recurrence of chorea was 2.1 years compared with 1.2 years to second
      recurrence. Established rheumatic heart disease developed in 58% of cases and was
      more likely in those presenting with acute carditis, although most people who
      developed rheumatic heart disease did not have evidence of acute carditis with
      chorea. Differences in the patterns of chorea and other manifestations of acute
      rheumatic fever in different populations may hold clues to its pathogenesis. Long
      term adherence to secondary prophylaxis is crucial following all episodes of
      acute rheumatic fever, including chorea, to prevent recurrence.

PMID- 10086944
TI  - Mothering to death.
AB  - Three families are described in which the healthy only child was, from early
      childhood, put to bed and treated as if ill, dependent, and incapable. This
      abnormal mothering continued for 28, 45, and 48 years, respectively, and the
      children died as disabled adults. In each case, the three mothers evaded medical,
      educational, and social services. The origins of their behaviour are examined,
      and the links with more common forms of separation anxiety, school refusal, and
      perceived and factitious illness are discussed.

PMID- 10086945
TI  - The prevalence and distribution of bruising in babies.
AB  - AIM: To obtain a prevalence rate and determine the distribution of accidental
      bruising in babies. METHODS: 177 babies aged 6-12 months were examined naked to
      look for bruises. They were seen in health visitor hearing test clinics and child
      health surveillance clinics. The site, size, shape, and colour of bruises were
      recorded on a skin map, and the parent's explanation noted. Any other injury was
      recorded. Data collection included the baby's age, mobility and weight,
      demographic details, and health visitor concerns. RESULTS: Twenty two babies had
      bruises, giving a prevalence rate of 12%. There was a total of 32 bruises, 15
      babies had one bruise. All bruises were found on the front of the body and were
      located over bony prominences. Twenty five of the bruises were on the face and
      head, and seven were on the shin. The babies with bruises on the shin were
      mobile. There was a highly significant increase in bruises with increase in
      mobility. CONCLUSIONS: The study has produced a prevalence and distribution of
      bruising in babies and sets a baseline from which to work when assessing bruises.
      It also tested out the methodology, which could be used in further research,
      particularly of younger babies. Clinicians need to assess a baby's level of
      development when considering whether a bruise is accidental.

PMID- 10086946
TI  - Partial remission phase of diabetes in children younger than age 10 years.
AB  - There is renewed interest in the phase of partial remission in recently diagnosed
      diabetes because of the potential for pharmacological and immune intervention to
      preserve beta cell function. 95 children younger than 10 years were investigated
      to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at
      diagnosis, and ethnicity on the frequency of remission and insulin requirements
      during the first two years after diagnosis. Partial remission was defined as a
      requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in
      41 patients, with no differences for children aged 2-4 years and those aged 5-9
      years. None of the five children aged < 2 years remitted. Forty five of 95
      children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood
      pH < 7.25). In this number of children we were unable to show a statistical
      difference in the rate of remission with respect to DKA, admission to hospital at
      diagnosis, sex, or South Asian ethnic background. There were no differences in
      insulin requirements between the different groups by the end of two years and at
      that time seven of the children required insulin < 0.5 U/kg/day. The results
      suggest that even in preschool children there is potential for attempting to
      preserve beta cell function.

PMID- 10086947
TI  - Urinary excretion of pyridinium crosslinks in healthy 4-10 year olds.
AB  - Urinary pyridinoline and deoxypyridinoline, pyridinium crosslinks released during
      breakdown of mature collagen, might serve as useful markers of bone resorption.
      Before their role can be identified, reference values must be established. In
      this study, free pyridinoline (f-Pyr), free deoxypyridinoline (f-DPyr), and
      creatinine (Cr) were measured in first morning void urine samples from 250 girls
      and 265 boys between the ages of 4 and 10 years. Overall, there was a decrease in
      f-Pyr:Cr and f-DPyr:Cr ratios with increasing age in both sexes, but there was a
      wide range of values for individuals of similar ages. Further studies are
      required to assess whether urinary pyridinium crosslink excretion is sufficiently
      deranged in conditions affecting bone metabolism for the measurement of these
      compounds to be of clinical value.

PMID- 10086949
TI  - Xylitol and acute otitis media 

PMID- 10086948
TI  - Generalised uridine diphosphate galactose-4-epimerase deficiency.
AB  - The generalised form of epimerase deficiency galactosaemia has been described in
      only two children from unrelated families. Their progress is reported and three
      other affected children from these families are described. The initial
      presentation was similar to classic galactosaemia. Despite treatment all have
      shown poor growth and moderate learning difficulties. Three have sensorineural
      deafness and four have pronounced dysmorphic features. The two older female
      patients have normal pubertal development.

PMID- 10086950
TI  - Differential avian and human tuberculin skin testing in non-tuberculous
      mycobacterial infection.
AB  - OBJECTIVE: To determine the sensitivity of differential avian and human delayed
      type hypersensitivity skin testing in the diagnosis of non-tuberculous
      mycobacterial lymphadenitis. METHOD: Retrospective review of all patients with
      culture proved non-tuberculous mycobacterial lymph node infections who also had
      differential avian and human skin testing performed over a 10 year period from
      1986 to 1996. RESULTS: One hundred and twenty four patients had non-tuberculous
      mycobacteria isolated from lymph nodes over this period, 59 of whom had
      differential skin testing performed. The sensitivity of a response of >/= 10 mm
      to the avian precipitin was 58 of 59. No patient had both a negative human and
      avian Mantoux. The sensitivity of the human Mantoux alone for diagnosing non
      tuberculous mycobacterial infection was 81% for a response of >/= 5 mm and 66%
      for >/= 10 mm. Ten patients had a 0 human response. Fifty five of the 59 patients
      had an avian response at least 2 mm greater than the human response. CONCLUSION:
      The avian Mantoux is a very sensitive method of diagnosing non-tuberculous
      mycobacterial infection in children. The human Mantoux is not sensitive enough to
      be used alone as a surrogate to diagnose non-tuberculous mycobacterial infection.

PMID- 10086951
TI  - Henoch-Schonlein purpura.

PMID- 10086952
TI  - Recent insights into hyperventilation from the study of Rett syndrome.

PMID- 10086953
TI  - Antimicrobial prophylaxis.

PMID- 10086954
TI  - Who needs chest physiotherapy? Moving from anecdote to evidence.

PMID- 10086955
TI  - Notes on paediatrics: cardiorespiratory disease 

PMID- 10086956
TI  - Pediatric skeletal scintigraphy with multimodality imaging correlations 

PMID- 10086957
TI  - Supportive care of children with cancer 

PMID- 10086958
TI  - AMPD1 gene mutation in congestive heart failure: new insights into the
      pathobiology of disease progression.

PMID- 10086959
TI  - Minimally invasive coronary artery bypass grafting: an experimental perspective.

PMID- 10086960
TI  - Inertia of success. A response to minimally invasive coronary bypass: a
      dissenting opinion.

PMID- 10086961
TI  - Genome-wide linkage analyses of systolic blood pressure using highly discordant
      siblings.
AB  - BACKGROUND: Elevated blood pressure is a risk factor for cardiovascular,
      cerebrovascular, and renal diseases. Complex mechanisms of blood pressure
      regulation pose a challenge to identifying genetic factors that influence
      interindividual blood pressure variation in the population at large. METHODS AND
      RESULTS: We performed a genome-wide linkage analysis of systolic blood pressure
      in humans using an efficient, highly discordant, full-sibling design. We
      identified 4 regions of the human genome that show statistical significant
      linkage to genes that influence interindividual systolic blood pressure variation
      (2p22.1 to 2p21, 5q33.3 to 5q34, 6q23.1 to 6q24.1, and 15q25.1 to 15q26.1). These
      regions contain a number of candidate genes that are involved in physiological
      mechanisms of blood pressure regulation. CONCLUSIONS: These results provide both
      novel information about genome regions in humans that influence interindividual
      blood pressure variation and a basis for identifying the contributing genes.
      Identification of the functional mutations in these genes may uncover novel
      mechanisms for blood pressure regulation and suggest new therapies and prevention
      strategies.

PMID- 10086962
TI  - Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking:
      a mechanism for arterial thrombosis and myocardial infarction.
AB  - BACKGROUND: Effective endogenous fibrinolysis requires rapid release of tissue
      plasminogen activator (tPA) from the vascular endothelium. Smoking is a known
      risk factor for arterial thrombosis and myocardial infarction, and it causes
      endothelial dysfunction. We therefore examined the effects of cigarette smoking
      on substance P-induced tPA release in vivo in humans. METHODS AND RESULTS: Blood
      flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers
      and 12 age- and sex-matched nonsmokers who received unilateral brachial artery
      infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers,
      substance P caused dose-dependent increases in blood flow and local release of
      plasma tPA antigen and activity (P<0.001 for all) but had no effect on the local
      release of plasminogen activator inhibitor type 1. Compared with nonsmokers,
      increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and
      activity (P<0.001) caused by substance P were reduced in smokers. The area under
      the curve for release of tPA antigen and activity decreased by 51% and 53%,
      respectively. CONCLUSIONS: Cigarette smoking causes marked inhibition of
      substance P-induced tPA release in vivo in humans. This provides an important
      mechanism whereby endothelial dysfunction may increase the risk of
      atherothrombosis through a reduction in the acute fibrinolytic capacity.

PMID- 10086963
TI  - Mechanisms of death in the CABG Patch trial: a randomized trial of implantable
      cardiac defibrillator prophylaxis in patients at high risk of death after
      coronary artery bypass graft surgery.
AB  - BACKGROUND: The CABG Patch trial compared prophylactic implantable cardiac
      defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary
      bypass surgery patients who had a left ventricular ejection fraction <0.36 and an
      abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group
      patients and 96 deaths among the 454 control group patients, a hazard ratio of
      1.07 (P=0.63). The mechanisms of death were classified, and hypotheses were
      tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac
      deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator
      Implantation Trial (MADIT). METHODS AND RESULTS: The 198 deaths in the trial were
      reviewed by an independent Events Committee and classified by the method of
      Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths
      (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group
      and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes.
      Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and
      4.0% in the ICD group (P=0. 057). Cumulative nonarrhythmic cardiac mortality at
      42 months was 12. 4% in the control group and 13.0% in the ICD group (P=0.275).
      Death due to pump failure was significantly associated with death >1 hour from
      the onset of symptoms, dyspnea within 7 days of death, and overt heart failure
      within 7 days of death. CONCLUSIONS: In the CABG Patch Trial, ICD therapy reduced
      arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because
      71% of the deaths were nonarrhythmic, total mortality was not significantly
      reduced.

PMID- 10086964
TI  - Common variant in AMPD1 gene predicts improved clinical outcome in patients with
      heart failure.
AB  - BACKGROUND: This study was undertaken to identify gene(s) that may be associated
      with improved clinical outcome in patients with congestive heart failure (CHF).
      The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We
      hypothesized that inheritance of the mutant AMPD1 allele is associated with
      increased probability of survival without cardiac transplantation in patients
      with CHF. METHODS AND RESULTS: AMPD1 genotype was determined in 132 patients with
      advanced CHF and 91 control reference subjects by use of a polymerase chain
      reaction-based, allele-specific oligonucleotide detection assay. In patients with
      CHF, those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1 allele
      (AMPD1 +/- or -/-, respectively) experienced a significantly longer duration of
      heart failure symptoms before referral for transplantation evaluation than CHF
      patients homozygous for the wild-type allele (AMPD1 +/+; n=111; 7.6+/-6.5 versus
      3.2+/-3.6 years; P<0.001). The OR of surviving without cardiac transplantation
      >/=5 years after initial hospitalization for CHF symptoms was 8.6 times greater
      (95% CI: 3.05, 23.87) in those patients carrying >/=1 mutant AMPD1 allele than in
      those carrying 2 wild-type AMPD1 +/+ alleles. CONCLUSIONS: After the onset of CHF
      symptoms, the mutant AMPD1 allele is associated with prolonged probability of
      survival without cardiac transplantation. The mechanism by which the presence of
      the mutant AMPD1 allele may modify the clinical phenotype of heart failure
      remains to be determined.

PMID- 10086965
TI  - Cell death in acromegalic cardiomyopathy.
AB  - BACKGROUND: Prolonged untreated acromegaly leads to a nonspecific myopathy
      characterized by ventricular dysfunction and failure. However, the mechanisms
      responsible for the alterations of cardiac pump function remain to be defined.
      Because cell death is implicated in most cardiac disease processes, the
      possibility has been raised that myocyte apoptosis may occur in the acromegalic
      heart, contributing to the deterioration of ventricular hemodynamics. METHODS AND
      RESULTS: Ten acromegalic patients with diastolic dysfunction and 4 also with
      systolic dysfunction were subjected to electrocardiography, Holter monitoring, 2
      dimensional echocardiography, cardiac catheterization, and biventricular and
      coronary angiography before surgical removal of a growth hormone-secreting
      pituitary adenoma. Endomyocardial biopsies were obtained and analyzed
      quantitatively in terms of tissue scarring and myocyte and nonmyocyte apoptosis.
      Myocardial samples from papillary muscles of patients who underwent valve
      replacement for mitral stenosis were used for comparison. The presence of
      apoptosis in myocytes and interstitial cells was determined by confocal
      microscopy with the use of 2 histochemical methods, consisting of terminal
      deoxynucleotidyl transferase (TdT) assay and Taq probe in situ ligation.
      Acromegaly was characterized by a 495-fold and 305-fold increase in apoptosis of
      myocytes and nonmyocytes, respectively. The magnitude of myocyte apoptosis
      correlated with the extent of impairment in ejection fraction and the duration of
      the disease. A similar correlation was found with the magnitude of collagen
      accumulation, indicative of previous myocyte necrosis. Myocyte death was
      independent from the hormonal levels of growth hormone and insulin-like growth
      factor-1. Apoptosis of interstitial cells did not correlate with ejection
      fraction. CONCLUSIONS: Myocyte cell death, apoptotic and necrotic in nature, may
      be critical for the development of ventricular dysfunction and its progression to
      cardiac failure with acromegaly.

PMID- 10086966
TI  - Prognostic value of nocturnal Cheyne-Stokes respiration in chronic heart failure.
AB  - BACKGROUND: Nocturnal Cheyne-Stokes respiration (CSR) occurs frequently in
      patients with chronic heart failure (CHF), and it may be associated with
      sympathetic activation. The aim of the present study was to evaluate whether CSR
      could affect prognosis in patients with CHF. METHODS AND RESULTS: Sixty-two CHF
      patients with left ventricular ejection fraction </=35%, in NYHA class II to III,
      underwent clinical evaluation, Doppler echocardiography, ergospirometry,
      phenylephrine test, Holter recording, and a sleep study to evaluate the
      occurrence of CSR, expressed as percentage of periodic breathing, and
      apnea/hypopnea index (AHI) (ie, the number of apneas and hypopneas per hour of
      recording). During a mean follow-up of 28+/-13 months, 15 patients died of
      cardiac causes. Nonsurvivors were in a higher NYHA functional class than
      survivors (P<0.001) and had a more depressed left ventricular ejection fraction
      (P<0.03), a shorter deceleration time of early filling (P<0. 05), larger left and
      right atria (P<0.05 and P<0.02, respectively) and a lower peak V(O2) (P<0.05).
      Nonsurvivors also spent a greater percentage of the night in periodic breathing
      (P<0.01) with a greater AHI (P<0.03) and showed lower values of diurnal
      baroreflex sensitivity (P<0.05) and of heart rate variability (sdNN: P<0.01).
      Multivariate analysis revealed the AHI (chi2, 10.4; P<0.01), followed by left
      atrial area (chi2, 5.7; P<0.01), as the only independent and additional
      predictors of subsequent cardiac death. Patients at very high risk for fatal
      outcome could be identified by an AHI >/=30/h and left atria >/=25 cm2.
      CONCLUSIONS: The AHI is a powerful independent predictor of poor prognosis in
      clinically stable patients with CHF. The presence of an AHI >/=30/h adds
      prognostic information compared with other clinical, echocardiographic, and
      autonomic data and identifies patients at very high risk for subsequent cardiac
      death.

PMID- 10086967
TI  - Effect of right atrial isthmus ablation on the occurrence of atrial fibrillation:
      observations in four patient groups having type I atrial flutter with or without
      associated atrial fibrillation.
AB  - BACKGROUND: The goal of this study was to test the hypothesis that the occurrence
      of atrial fibrillation (AF), in at least some patients with coexisting type I
      atrial flutter (AFL), is based on macro-reentry around the tricuspid valve
      orifice, including the right atrial (RA) isthmus, by evaluation of AF recurrences
      after successful ablation of AFL. METHODS AND RESULTS: Eighty-two consecutive
      patients with type I AFL, with or without concomitant AF, underwent
      radiofrequency ablation (RFA) of the RA isthmus by an anatomical approach. The
      results were analyzed in 4 groups of patients: group 1 (only AFL; 29 patients),
      group 2 (AFL >AF; 22 patients), group 3 (AF >AFL; 15 patients), and group 4
      (developing AFL while receiving class IC antiarrhythmic drug therapy for AF, the
      "class IC atrial flutter"; 16 patients). In all groups, RFA of type I AFL was
      performed with a high (>/=93%) procedural success rate. In group 1, only 2
      patients (8%) had AF after (18+/-14 months) AFL ablation. These figures were 38%
      (20+/-14 months) and 86% (13+/-8 months) in groups 2 and 3, respectively. Group 4
      patients (4+/-2 months) had a 73% freedom of AF recurrences with continuation of
      the class IC agent. CONCLUSIONS: The low incidence of new AF during long-term
      follow-up after RFA of type I AFL makes it unlikely that radiofrequency lesions
      promote the development of AF. The impact of isthmus ablation on AF recurrences
      differs according to the clinically predominant atrial arrhythmia and suggests a
      possible role of the RA isthmus in the occurrence of AF in some patients.
      Ablation of class IC atrial flutter in patients with therapy-resistant AF is a
      novel approach to management of this patient subset. Careful classification of AF
      patients plays a role in the selection of the site of ablation therapy.

PMID- 10086968
TI  - Atrial fibrillation detection and R-wave synchronization by Metrix implantable
      atrial defibrillator: implications for long-term efficacy and safety. The Metrix
      Investigators.
AB  - BACKGROUND: The long-term efficacy of atrial fibrillation (AF) detection and R
      wave synchronization are critical safety requirements for the development of an
      implantable atrial defibrillator (IAD) for treatment of AF. METHODS AND RESULTS:
      The long-term efficacy of the Metrix IAD for AF detection and R-wave
      synchronization was tested in 51 patients. The mean duration of follow-up was
      259+/-138 days (72 to 613 days). AF detection tests were performed 2240 times
      during observed operation with 100% specificity and 92.3% sensitivity for
      differentiation between sinus rhythm and AF; 2219 episodes and their electrograms
      stored in the device during AF detection were analyzed. The positive predictive
      value of the AF detection algorithm was 97.4% (lower 95% confidence limit [CL],
      94.5%) in the out-of-hospital setting. A total of 242 435 R waves were analyzed
      for R-wave synchronization. Of these, 49% were marked for synchronized shock
      delivery, 82% of sinus rhythm and 36% of AF R waves, respectively. All shock
      markers were properly synchronized and within the R wave (overall synchronization
      accuracy, 100%; lower 95% CL, 99.999%). Overall, 3719 shocks have been delivered
      via the IAD with no instance of unsynchronized shock delivery or any episode of
      proarrhythmia. The observed proarrhythmic risk was 0%, with an estimated maximum
      proarrhythmic risk of 0.084% per shock (95% upper CL). CONCLUSIONS: The Metrix
      IAD can appropriately detect AF with a high specificity and sensitivity and
      reliably synchronize within a suitable R wave for shock delivery to minimize the
      risk of ventricular proarrhythmia.

PMID- 10086969
TI  - Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal
      syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal
      Syncope International Study.
AB  - BACKGROUND: Etilefrine is an alpha-agonist agent with a potent vasoconstrictor
      effect, which is potentially useful in preventing vasovagal syncope by reducing
      venous pooling and/or by counteracting reflex arteriolar vasodilatation. The
      present multicenter, randomized, placebo-controlled study was designed to
      evaluate the efficacy of this drug for the long-term management of patients with
      recurrent vasovagal syncope. METHODS AND RESULTS: In the 20 participating
      centers, 126 patients with recurrent vasovagal syncope (at least 3 episodes in
      the last 2 years) and a positive baseline head-up tilt response were randomly
      assigned to placebo (63 patients) or etilefrine at a dosage of 75 mg/d (63
      patients) and were followed up for 1 year or until syncope recurred. The primary
      end-point of the study was the first recurrence of syncope. There were no
      differences between the 2 study groups in the patients' baseline characteristics.
      During follow-up, the group treated with etilefrine had a similar incidence of
      first syncopal recurrence to that of placebo group both in the intention-to-treat
      analysis (24% versus 24%) and in on- treatment analysis (26% versus 24%).
      Moreover, the median time to the first syncopal recurrence did not significantly
      differ between the 2 study groups (106 days in the etilefrine arm and 112 days in
      the placebo arm). CONCLUSIONS: Oral etilefrine is not superior to placebo in
      preventing spontaneous episodes of vasovagal syncope. Randomized controlled
      studies are essential to assess the real usefulness of any proposed therapy for
      patients with vasovagal syncope.

PMID- 10086970
TI  - QT dispersion as an attribute of T-loop morphology.
AB  - BACKGROUND: The suggestion that increased QT dispersion (QTD) is due to increased
      differences in local action potential durations within the myocardium is wanting.
      An alternative explanation was sought by relating QTD to vectorcardiographic T
      loop morphology. METHODS AND RESULTS: The T loop is characterized by its
      amplitude and width (defined as the spatial angle between the mean vectors of the
      first and second halves of the loop). We reasoned that small, wide
      ("pathological") T loops produce larger QTD than large, narrow ("normal") loops.
      To quantify the relationship between QTD and T-loop morphology, we used a program
      for automated analysis of ECGs and a database of 1220 standard simultaneous 12
      lead ECGs. For each ECG, QT durations, QTD, and T-loop parameters were computed.
      T-loop amplitude and width were dichotomized, with 250 microV (small versus large
      amplitudes) and 30 degrees (narrow versus wide loops) taken as thresholds. Over
      all 1220 ECGs, QTDs were smallest for large, narrow T loops (54.2+/-27.1 ms) and
      largest for small, wide loops (69. 5+/-33.5 ms; P<0.001). CONCLUSIONS: QTD is an
      attribute of T-loop morphology, as expressed by T-loop amplitude and width.

PMID- 10086971
TI  - C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated
      mutation in cardiac event occurrence.
AB  - BACKGROUND: The long-QT syndrome (LQTS) is a genetically heterogeneous disease in
      which 4 genes encoding ion-channel subunits have been identified. Most of the
      mutations have been determined in the transmembrane domains of the cardiac
      potassium channel genes KCNQ1 and HERG. In this study, we investigated the 3'
      part of HERG for mutations. METHODS AND RESULTS: New specific primers allowed the
      amplification of the 3' part of HERG, the identification of 2 missense mutations,
      S818L and V822 M, in the putative cyclic nucleotide binding domain, and a 1-bp
      insertion, 3108+1G. Hypokalemia was a triggering factor for torsade de pointes in
      2 of the probands of these families. Lastly, in a large family, a maternally
      inherited G to A transition was found in the splicing donor consensus site of
      HERG, 2592+1G-A, and a paternally inherited mutation, A341E, was identified in
      KCNQ1. The 2 more severely affected sisters bore both mutations. CONCLUSIONS: The
      discovery of mutations in the C-terminal part of HERG emphasizes that this region
      plays a significant role in cardiac repolarization. Clinical data suggests that
      these mutations may be less malignant than mutations occurring in the pore
      region, but they can become clinically significant in cases of hypokalemia. The
      first description of 2 patients with double heterozygosity associated with a
      dramatic malignant phenotype implies that genetic analysis of severely affected
      young patients should include an investigation for >1 mutation in the LQT genes.

PMID- 10086972
TI  - Relation of weight and rate of increase in weight during childhood and
      adolescence to body size, blood pressure, fasting insulin, and lipids in young
      adults. The Minneapolis Children's Blood Pressure Study.
AB  - BACKGROUND: Weight gain is of concern during early development because adult
      obesity and its cardiovascular consequences appear to have their origins during
      childhood. Insulin resistance is known to be related to obesity. Thus, weight
      gain beginning in childhood may influence the development of insulin-induced
      cardiovascular risk during adulthood. METHODS AND RESULTS: We monitored 679
      individuals from 7.7+/-0.1 years of age with repeated measures of height, weight,
      and systolic blood pressure (SBP) until 23.6+/-0.2 years of age, when blood
      samples were obtained for measurements of insulin and lipids. Initial childhood
      weight, body mass index (BMI), and height were significantly correlated with
      young adult weight, BMI, and height and with fasting insulin, lipids, and SBP.
      The increases in weight and BMI but not height during childhood were
      significantly related to the young adult levels of insulin, lipids, and SBP.
      CONCLUSIONS: These data suggest that weight gain in excess of normal growth
      during childhood is a determinant of adult cardiovascular risk. The finding in
      multiple linear regression analysis that weight gain during childhood rather than
      the childhood weight at 7.7 years of age is significantly related to young adult
      risk factors suggests that a reduction in weight gain could reduce subsequent
      levels of cardiovascular risk.

PMID- 10086973
TI  - Cellular effects of beta-particle delivery on vascular smooth muscle cells and
      endothelial cells: a dose-response study.
AB  - BACKGROUND: Although endovascular radiotherapy inhibits neointimal hyperplasia,
      the exact cellular alterations induced by beta irradiation remain to be
      elucidated. METHODS AND RESULTS: We investigated in vitro the ability of 32P
      labeled oligonucleotides to alter (1) proliferation of human and porcine vascular
      smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs),
      (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration,
      and (5) cell phenotype and morphological features. beta radiation significantly
      reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2.15 Gy) in a dose
      dependent manner. Exposure to beta emission interfered with cell cycle
      progression, with induction of G0/G1 arrest in VSMCs, without evidence of cell
      viability alteration, apoptosis, or ultrastructural changes. This strategy also
      proved to efficiently inhibit VSMC migration by 80% and induce contractile
      phenotype appearance, as shown by the predominance of alpha-actin immunostaining
      in beta-irradiated cells compared with control cells. CONCLUSIONS: 32P-labeled
      oligonucleotide was highly effective in inhibiting proliferation of both VSMCs
      and ECs in a dose-dependent fashion, with ECs showing a higher resistance to
      these effects. beta irradiation-induced G1 arrest was not associated with
      cytotoxicity and apoptosis, thus demonstrating a potent cytostatic effect of beta
      based therapy. This effect, coupled to that on VSMC migration inhibition and the
      appearance of a contractile phenotype, reinforced the potential of ionizing
      radiation to prevent neointima formation after angioplasty.

PMID- 10086974
TI  - Aldosterone, not estradiol, is the physiological agonist for rapid increases in
      cAMP in vascular smooth muscle cells.
AB  - BACKGROUND: Steroid-induced gene regulation in the endocrine tissues and vascular
      wall is achieved through the interaction of specific receptor proteins and
      promoters of target genes. In addition to these delayed steroid actions, rapid
      effects of steroids have been reported in various tissues that were clearly
      incompatible with the classic theory of genomic steroid action. METHODS AND
      RESULTS: Because high doses of 17beta-estradiol have been shown to modulate
      intracellular cAMP levels in vascular smooth muscle cells, steroid-induced
      stimulation of adenylate cyclase stimulation and phosphorylation of cAMP response
      element binding protein was investigated in porcine coronary artery vascular
      smooth muscle cells. Aldosterone induces a approximately 1.5- to 2.5-fold
      increase in intracellular cAMP levels (EC50 approximately 0.01 to 0.1 nmol/L)
      within 1 minute, whereas 17beta-estradiol and hydrocortisone act only at
      supraphysiological concentrations (10 micromol/L). Aldosterone-induced changes in
      intracellular cAMP are calcium dependent; they are not blocked by inhibitors of
      mineralocorticoid receptors, transcription, or protein synthesis. In addition,
      aldosterone induces a time-dependent phosphorylation of cAMP response element
      binding protein with potential transcriptional importance. CONCLUSIONS: A
      nongenomic modulation of vascular smooth muscle cells by aldosterone is
      consistent with the data that aldosterone, not estrogen, is the physiological
      stimulus for cAMP.

PMID- 10086975
TI  - Tissue expression and immunolocalization of tumor necrosis factor-alpha in
      postinfarction dysfunctional myocardium.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is markedly elevated in
      advanced heart failure. It is not known whether tissue TNF-alpha is elevated in
      the common setting of myocardial infarction leading to heart failure and what the
      source of TNF-alpha is. To determine this, we studied the expression and protein
      localization of TNF-alpha and its 2 main receptors (TNF-R1/R2) in a rat model of
      large infarction. METHODS AND RESULTS: Male rats were randomized to proximal left
      anterior descending ligation. The animals were killed on days 1, 3, 10, and 35
      after ligation to examine gene expression and protein production of TNF-alpha and
      TNF-R1/R2 from the infarct, peri-infarct, and contralateral zones of infarcted
      heart. There was increased TNF-alpha mRNA production throughout the myocardium at
      day 1, and detectable expression persisted to day 35 after myocardial infarction.
      The expression of this cytokine is not confined strictly to the infarct or peri
      infarct zones but is expressed by cardiac myocytes within the myocardium in the
      contralateral normal zone. Changes in gene expression are mirrored initially by
      augmented protein production within the myocytes. Levels of TNF-alpha protein in
      the infarct and peri-infarct zones rose early to 8- to 10-fold above normal
      levels and rose to 4- to 5-fold in the contralateral zone. Finally, expression of
      the TNF-R1 mRNA transcripts was upregulated at days 3 and 10 after ligation in
      the infarct and peri-infarct zones, suggesting that the signal transduction
      pathways necessary for TNF-alpha in the heart remain intact as TNF-alpha
      biosynthesis increases. CONCLUSIONS: TNF-alpha is present early in a model of
      large myocardial infarction and is sustained into the later stage within the
      myocardium. Expression of this cytokine is not only confined strictly to the
      infarct or peri-infarct zone but is expressed by cardiac myocytes within the
      myocardium contralateral to the infarct. Therefore TNF-alpha production forms a
      part of an important intrinsic myocardial stress response system to injury.

PMID- 10086976
TI  - Cellular and ionic basis for T-wave alternans under long-QT conditions.
AB  - BACKGROUND: T-wave alternans (TWA), an ECG phenomenon characterized by beat-to
      beat alternation of the morphology, amplitude, and/or polarity of the T wave, is
      commonly observed in the acquired and congenital long-QT syndromes (LQTS). This
      study examines the cellular and ionic basis for TWA induced by rapid pacing under
      conditions mimicking the LQT3 form of the congenital LQTS in an arterially
      perfused canine left ventricular wedge preparation. METHODS AND RESULTS:
      Transmembrane action potentials from epicardial, M, and endocardial cells and 6
      to 8 intramural unipolar electrograms were simultaneously recorded together with
      a transmural ECG and isometric tension development. In the presence of sea
      anemone toxin (ATX-II; 20 nmol/L), an increase in pacing rate (from a cycle
      length [CL] of 500 to 400 to 250 ms) produced a wide spectrum of T-wave and
      mechanical alternans. Acceleration to CLs of 400 to 300 ms produced mild to
      moderate TWA principally due to beat-to-beat alternation of repolarization of
      cells in the M region. Transmural dispersion of repolarization during alternans
      was exaggerated during alternate beats. Acceleration to CLs of 300 to 250 ms
      caused more pronounced beat-to-beat alternation of action potential duration
      (APD) of the M cell, resulting in a reversal of repolarization sequence across
      the ventricular wall, leading to alternation in the polarity of the T wave. The
      peak of the negative T waves coincided with repolarization of the M region,
      whereas the end of the negative T wave coincided with the repolarization of
      epicardium. In almost all cases, electrical alternans was concordant with
      mechanical alternans. Torsade de pointes occurred after an abrupt acceleration of
      CL, which was associated with marked TWA. Both ryanodine and low [Ca2+]o
      completely suppressed alternans of the T wave, APD, and contraction, suggesting a
      critical role for intracellular Ca2+ cycling in the maintenance of TWA.
      CONCLUSIONS: Our results suggest that TWA observed at rapid rates under long-QT
      conditions is largely the result of alternation of the M-cell APD, leading to
      exaggeration of transmural dispersion of repolarization during alternate beats,
      and thus the potential for development of torsade de pointes. Our data also
      suggest that unlike transient forms of TWA that damp out quickly and depend on
      electrical restitution factors, the steady-state electrical and mechanical
      alternans demonstrated in this study appears to be largely the result of beat-to
      beat alternans of [Ca2+]i.

PMID- 10086977
TI  - Conduction disturbances and increased atrial vulnerability in Connexin40
      deficient mice analyzed by transesophageal stimulation.
AB  - BACKGROUND: Recently, it has been reported that connexin40 (Cx40) deficiency in
      targeted mouse mutants is associated with a prolongation of P-wave and QRS
      complex duration on surface electrograms. The specific effects of Cx40 deficiency
      on sinus node function, sinoatrial, and atrioventricular conduction properties as
      well as on atrial vulnerability have not yet been investigated systematically by
      electrophysiological analysis. METHODS AND RESULTS: Fifty-two mice (18 Cx40(+/+),
      15 Cx40(+/-), and 19 Cx40(-/-) mice) were subjected to rapid atrial
      transesophageal stimulation after anesthesia with avertin. A significant
      prolongation of sinus node recovery time was noticed in Cx40(-/-) mice compared
      with Cx40(+/-) and Cx40(+/+) mice (287.8+/-109.0 vs 211.1+/-61.8 vs 204.4+/-60.9
      ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer
      atrial pacing cycle lengths in Cx40(-/-) mice than in Cx40(+/-) or Cx40(+/+) mice
      (93. 3+/-11.8 vs 83.9+/-9.7 vs 82.8+/-8.0 ms, P<0.05). Analysis of 27 Cx40(-/-)
      mice showed a significant increase in intra-atrial conduction time and
      atrioventricular conduction time compared with 52 Cx40(+/-) and 31 wild-type
      (Cx40(+/+)) mice. Furthermore, in Cx40(-/-) mice, atrial tachyarrhythmias could
      be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were
      inducible in heterozygous or wild-type mice. CONCLUSIONS: This study demonstrates
      that Cx40 deficiency is associated with sinoatrial, intra-atrial, and
      atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40
      deficiency results in increased atrial vulnerability and might contribute to
      arrhythmogenesis.

PMID- 10086978
TI  - Effect of biphasic shock duration on defibrillation threshold with different
      electrode configurations and phase 2 capacitances: prediction by upper-limit-of
      vulnerability determination.
AB  - BACKGROUND: The defibrillation threshold (DFT) may be affected by biphasic shock
      duration (BSD), electrode configuration, and capacitance. The upper limit of
      vulnerability (ULV) may be used to estimate the DFT. For different lead
      configurations and phase 2 capacitances, we investigated in 18 pigs whether the
      use of ULV may predict waveforms with lowest DFT. METHODS AND RESULTS: -DFT and
      ULV were determined by up-down protocols for 10 BSDs. ULVs were measured by T
      wave scanning during ventricular pacing (cycle length 500 ms). In protocol 1
      (n=6), a pectoral "active can" was combined with an electrode in the superior
      vena cava as common cathode and a right ventricle electrode as anode (AC+SVC). In
      protocol 2 and protocol 3 (n=6 each), only the "active can" was used as proximal
      electrode (AC). Capacitance was 150 microF during both phases in protocol 1 and
      protocol 3 but 150 microF (phase 1) and 300 microF (phase 2) in protocol 2. ULV
      and DFT demonstrated a linear correlation in each protocol (r=0.78 to 0.84).
      Lowest DFTs were found at 10 ms for AC+SVC and at 14 ms for AC (P<0.001). At
      optimal BSDs, voltage DFTs did not differ significantly between AC (527+/-57 V)
      and AC+SVC (520+/-70 V). Switching capacitors for phase 2 in a way that reduced
      leading-edge voltage by 50% while doubling capacity did not change BSD for
      optimal voltage DFT but increased minimum DFT from 527+/-57 V to 653+/-133 V
      (P=0.04). CONCLUSIONS: The BSD with lowest DFT is shorter for AC+SVC than for AC.
      There is no significant difference in voltage DFT between both at optimal BSD. A
      lower phase 2 capacitance reduces DFTs irrespective of BSD. Because strength
      duration curves for DFT and ULV correlate for different BSDs, lead systems, and
      phase 2 capacitances, ULV determination may allow the prediction of waveforms
      with lowest DFT.

PMID- 10086979
TI  - LAD stenosis detected by subsecond spiral CT.

PMID- 10086980
TI  - Stable incorporation of a lipophilic daunorubicin prodrug into apolipoprotein E
      exposing liposomes induces uptake of prodrug via low-density lipoprotein receptor
      in vivo.
AB  - Many tumors express elevated levels of low-density lipoprotein (LDL) receptors.
      Therefore, native LDL and synthetic LDL-like particles have been proposed as
      carriers for antineoplastic drugs. We demonstrated earlier that small
      apolipoprotein E (apoE)-exposing liposomes were specifically recognized by the
      LDL receptor. In this study, we incorporated a lipophilic derivative of
      daunorubicin (LAD) into the apoE liposomes. Up to 11 molecules of LAD could be
      incorporated per particle without significantly changing the size, lipid
      composition, and ability to bind apoE of the liposomes. The biological fate of
      the prodrug was largely determined by its carrier (70% of the initially
      incorporated LAD was still associated to the liposomes after 4 h of circulation
      in mice). Compared with free daunorubicin, the circulation half-life of the
      liposome-associated prodrug was substantially prolonged and undesired tissue
      disposition was reduced. The role of the LDL receptor in the metabolism of LAD
      loaded apoE liposomes was demonstrated in rats with up-regulated hepatic LDL
      receptors. In these rats, the liver uptake of the prodrug and carrier was
      increased 5-fold. The addition of apoE was essential for LDL receptor-mediated
      uptake of the drug-carrier complex. In LDL receptor-deficient mice, the
      circulation time of both the prodrug and the carrier increased approximately 2
      fold compared with wild-type mice. We conclude that LAD-loaded apoE liposomes
      constitute a stable drug-carrier complex that is well suited for LDL receptor
      mediated selective drug delivery to tumors.

PMID- 10086981
TI  - Response surface analysis of synergism between morphine and clonidine.
AB  - Graded doses of morphine sulfate and clonidine hydrochloride were administered
      intrathecally to mice that were then tested for antinociception in the 55 degrees
      C tail immersion test. The dose-effect relations of each compound were used in
      calculations that permitted the construction of a three-dimensional plot of the
      expected additive effect (vertical scale) against the planar domain of dose pairs
      representing combinations administered simultaneously. This additive response
      surface became the reference surface for viewing the actual effects produced by
      three different fixed-ratio combinations of the drugs that were used in our
      tests. Each combination produced effects significantly greater than indicated by
      the additive surface, thereby illustrating marked synergism and a method for
      quantifying the synergism. This quantification, measured by the value of the
      interaction index (alpha), was found to be dependent on the fixed-ratio
      combination; accordingly, the actual response surface could not be described by a
      single value of the index alpha. Furthermore, we found that application of the
      common method of isoboles gave estimates of the index that agreed well with those
      obtained from the more extensive surface analysis. These results confirm earlier
      studies, which found synergism for these drugs while also providing surface views
      of additivity and synergism that form the basis of isobolographic analysis.

PMID- 10086982
TI  - Comparison of effects of haloperidol administration on amphetamine-stimulated
      dopamine release in the rat medial prefrontal cortex and dorsal striatum.
AB  - Research has shown that there are important neurochemical differences between the
      mesocortical and mesostriatal dopamine systems. The work reported in this paper
      has sought to compare the regulation of dopamine release in the medial prefrontal
      cortex and the anterior caudate-putamen. In vivo microdialysis was used to
      recover dialysate fluid for subsequent assay for dopamine concentrations. The
      responses to D2 antagonist (haloperidol) administration, which has been shown to
      increase impulse-dependent dopamine release, were compared. Results demonstrated
      a diminished effect of systemic haloperidol administration on dopamine efflux in
      the prefrontal cortex. The responses to systemic administration of a nonimpulse
      dependent, transporter-mediated, dopamine releaser (d-amphetamine) were also
      contrasted. Results again demonstrated a diminished pharmacological effect in the
      cortex. The potential interaction of stimulation of these two types of dopamine
      release was examined by coadministration of these compounds. Haloperidol
      pretreatment dramatically potentiated the dopamine-releasing effect of
      amphetamine administration. This effect was observed in both the cortex and the
      striatum. Subsequent work demonstrated that this effect of haloperidol was
      mediated by D2-like receptors in the prefrontal cortex. These results are
      discussed in relation to other neurochemical and neuroanatomical studies
      demonstrating sparse densities of dopamine transporter sites and dopamine D2
      receptors in the cortex compared with the striatum. They demonstrate a functional
      correlate to the recently reported, largely extrasynaptic localization of
      dopamine transporter sites in the prefrontal cortex. Furthermore, they
      demonstrate the existence of cortical D2-like autoreceptors that may normally be
      "silent" under basal conditions.

PMID- 10086983
TI  - Glucocorticoid enhances interleukin-1-induced pressor response in freely moving
      rats through its effect on nitric oxide release.
AB  - We investigated whether changes in nitric oxide (NO) release might be responsible
      for the modulation by glucocorticoids of the pressor response to i.p. injection
      of interleukin-1beta (IL-1beta) in freely moving rats. In such rats, IL-1beta (10
      microgram/kg) induced a biphasic pressor response, with a rise in the plasma
      concentration of NOx (NO2(-) and NO3(-): metabolites of NO) during the second
      phase. Systemic pretreatment with an exogenous glucocorticoid, dexamethasone (0.5
      mg/kg), enhanced the second phase of the pressor response and completely
      suppressed the increase in plasma NOx. Treatment with Nomega-nitro-L-arginine
      methyl ester (L-NAME, a nonspecific NO synthase inhibitor), enhanced the pressor
      response while attenuating the increase in plasma NOx. After bilateral
      adrenalectomy, IL-1beta induced a smaller pressor response, but a larger increase
      in plasma NOx; dexamethasone reversed these changes. Our results suggest that
      endogenous NO moderates the pressor response to IL-1beta in freely moving rats,
      and that glucocorticoids enhance the IL-1beta-induced pressor response at least
      in part by reducing endogenous NO release.

PMID- 10086984
TI  - In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a
      specific marker reaction for cytochrome P-4503A4 activity in human liver
      microsomes.
AB  - The aim of this study was to evaluate the (3S)-3-hydroxylation and the N
      oxidation of quinidine as biomarkers for cytochrome P-450 (CYP)3A4 activity in
      human liver microsome preparations. An HPLC method was developed to assay the
      metabolites (3S)-3-hydroxyquinidine (3-OH-Q) and quinidine N-oxide (Q-N-OX)
      formed during incubation with microsomes from human liver and from Saccharomyces
      cerevisiae strains expressing 10 human CYPs. 3-OH-Q formation complied with
      Michaelis-Menten kinetics (mean values of Vmax and Km: 74.4 nmol/mg/h and 74.2
      microM, respectively). Q-N-OX formation followed two-site kinetics with mean
      values of Vmax, Km and Vmax/Km for the low affinity isozyme of 15.9 nmol/mg/h,
      76.1 microM and 0.03 ml/mg/h, respectively. 3-OH-Q and Q-N-OX formations were
      potently inhibited by ketoconazole, itraconazole, and triacetyloleandomycin.
      Isozyme specific inhibitors of CYP1A2, -2C9, -2C19, -2D6, and -2E1 did not
      inhibit 3-OH-Q or Q-N-OX formation, with Ki values comparable with previously
      reported values. Statistically significant correlations were observed between
      CYP3A4 content and formations of 3-OH-Q and Q-N-OX in 12 human liver microsome
      preparations. Studies with yeast-expressed isozymes revealed that only CYP3A4
      actively catalyzed the (3S)-3-hydroxylation. CYP3A4 was the most active enzyme in
      Q-N-OX formation, but CYP2C9 and 2E1 also catalyzed minor proportions of the N
      oxidation. In conclusion, our studies demonstrate that only CYP3A4 is actively
      involved in the formation of 3-OH-Q. Hence, the (3S)-3-hydroxylation of quinidine
      is a specific probe for CYP3A4 activity in human liver microsome preparations,
      whereas the N-oxidation of quinidine is a somewhat less specific marker reaction
      for CYP3A4 activity, because the presence of a low affinity enzyme is
      demonstrated by different approaches.

PMID- 10086985
TI  - Necessary role for ventral tegmental area adenylate cyclase and protein kinase A
      in induction of behavioral sensitization to intraventral tegmental area
      amphetamine.
AB  - In the present study, we investigated the effects of selective activation or
      inhibition of ventral tegmental area (VTA) adenylate cyclase (AC) and protein
      kinase A (PKA) on long-term sensitization induced by repeated intra-VTA or
      peripheral amphetamine (AMPH). Selective inhibition of AC by SQ 22,536 (9
      (tetrahydro-2-furanyl)-9H-purin-6-amine; 100 nmol/side bilateral into VTA) had no
      effect on acute basal locomotion but attenuated the locomotor stimulation induced
      by acute i.p. AMPH (1.5 mg/kg). Coinjection of SQ 22,536 (100 nmol/side) fully
      blocked the sensitization induced by repeated intra-VTA AMPH (15 nmol/side) but
      had no detectable effect on the sensitization induced by repeated i. p. AMPH.
      Persistent activation of AC by intra-VTA cholera toxin (500 ng/side) modestly
      increased acute locomotion and induced a robust sensitization to i.p. AMPH
      challenge 10 days after the last of three repeated VTA microinjections. Selective
      inhibition of PKA by Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine
      (Rp-cAMPS; 25 nmol/side) had no effect on acute basal or AMPH-stimulated
      locomotion. Coinjection of Rp-cAMPS (25 nmol/side) fully blocked the
      sensitization induced by repeated intra-VTA AMPH but had no effect on
      sensitization induced by repeated i.p. AMPH. Intra-VTA microinjection of the
      selective PKA activator Sp-adenosine-3',5'-cyclic monophosphothioate
      triethylamine (Sp-cAMPS; 25-100 nmol/side) dose-dependently stimulated acute
      locomotion and exerted synergistic effects on locomotor activity when coinfused
      into the VTA with AMPH but had no detectable effect on acute i.p. AMPH-induced
      locomotion. Repeated intra-VTA Sp-cAMPS did not induce sensitization to AMPH
      challenge but potentiated the sensitization induced by repeated i.p. AMPH. These
      results suggest that VTA cAMP signal transduction is necessary for the induction
      of persistent sensitization to intra-VTA amphetamine and that peripheral and
      intra-VTA AMPH may not induce behavioral sensitization by identical mechanisms.

PMID- 10086986
TI  - In vitro and in vivo characterization of intrinsic sympathomimetic activity in
      normal and heart failure rats.
AB  - Clinical studies conducted with carvedilol suggest that beta-adrenoceptor
      antagonism is an effective therapeutic approach to the treatment of heart
      failure. However, many beta-adrenoceptor antagonists are weak partial agonists
      and possess significant intrinsic sympathomimetic activity (ISA), which may be
      problematic in the treatment of heart failure. In the present study, the ISAs of
      bucindolol, xamoterol, bisoprolol, and carvedilol were evaluated and compared in
      normal rats [Sprague-Dawley (SD)], in rats with confirmed heart failure
      [spontaneously hypertensive heart failure (SHHF)], and in isolated neonatal rat
      cardiomyocytes. At equieffective beta1-adrenolytic doses, the administration of
      xamoterol and bucindolol produced a prolonged, equieffective, and dose-related
      increase in heart rate in both pithed SD rats (ED50 = 5 and 40 microgram/kg,
      respectively) and SHHF rats (ED50 = 6 and 30 microgram/kg, respectively). The
      maximum effect of both compounds in SHHF rats was approximately 50% of that
      observed in SD rats. In contrast, carvedilol and bisoprolol had no significant
      effect on resting heart rate in the pithed SD or SHHF rat. The maximum increase
      in heart rate elicited by xamoterol and bucindolol was inhibited by treatment
      with propranolol, carvedilol, and betaxolol (beta1-adrenoceptor antagonist) but
      not by ICI 118551 (beta2-adrenoceptor antagonist) in neonatal rat. When the beta
      adrenoceptor-mediated cAMP response was examined in cardiomyocytes, an identical
      partial agonist/antagonist response profile was observed for all compounds,
      demonstrating a strong correlation with the in vivo results. In contrast, GTP
      sensitive ligand binding and tissue adenylate cyclase activity were not sensitive
      methods for detecting beta-adrenoceptor partial agonist activity in the heart. In
      summary, xamoterol and bucindolol, but not carvedilol and bisoprolol, exhibited
      direct beta1-adrenoceptor-mediated ISA in normal and heart failure rats.

PMID- 10086987
TI  - Female gonadal hormones differentially modulate cocaine-induced behavioral
      sensitization in Fischer, Lewis, and Sprague-Dawley rats.
AB  - Evidence suggests the existence of genetic differences in cocaine sensitization
      in male rats. The present study was undertaken to investigate cocaine
      sensitization in female rats of genetically distinct inbred (Fischer 344 and
      Lewis) and outbred (Sprague-Dawley) strains. All female rats were bilaterally
      ovariectomized and randomly assigned to one of four experimental groups: 1)
      estradiol benzoate group, 2) progesterone group, 3) estradiol benzoate-plus
      progesterone group, and 4) ovariectomized group. Additional controls included
      sham-operated female rats, female rats that received a single oil injection, and
      female rats that received repeated oil injections. To determine gender-related
      differences in the acute and chronic effects of cocaine, data obtained from
      female rats were compared with those from strain- and weight-matched male rats.
      Estradiol benzoate-plus-progesterone female rats showed greater locomotor effect
      in response to an acute dose of cocaine and had more robust sensitization in
      response to repeated cocaine than did male rats. The bilateral removal of ovaries
      abolished cocaine sensitization. In all strains of rats studied, progesterone
      alone did not alter the ovariectomy-induced attenuation of cocaine behavior, but
      estrogen alone restored cocaine-induced behavioral sensitization. There were
      significant strain effects on the degree of gonadal hormonal-induced modulation
      of cocaine sensitization in female rats. Female Lewis rats were extremely
      sensitive to repeated-cocaine effects, whereas the Fischer 344 female rats showed
      only marginal effects. The Sprague-Dawley rats ranked intermediate in their
      behavioral sensitivity. The present study strongly supports the hypothesis that
      female rats are more sensitive to both acute and chronic behavioral effects of
      cocaine than are male rats and that the effects are strain dependent. It also
      shows that estrogen plays an important role in the increased sensitivity of
      female rats to cocaine sensitization. Together, these data indicate significant
      interactions between ovarian steroid hormones and genetic factors in cocaine
      induced behavioral effects.

PMID- 10086988
TI  - Multiplicity of the H+-dependent transport mechanism of dipeptide and anionic
      beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane.
AB  - To elucidate the transport characteristics of the H+/dipeptide carrier that
      recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake
      behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border
      membrane vesicles. The results show that 1) both the uptake of ceftibuten and
      that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic
      compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten
      uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar
      uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even
      in the presence of 20 mM Gly-Sar. The results provide an evidence that several
      transporters with different features are potentially responsible for the uptake
      of beta-lactam antibiotics into the intestinal cells. It is suggested that the
      dianionic beta-lactam antibiotics that carry a net negative charge such as
      ceftibuten use multiple H+-dependent transport systems for absorption.

PMID- 10086989
TI  - Anti-herpes simplex virus activity of moronic acid purified from Rhus javanica in
      vitro and in vivo.
AB  - Rhus javanica, a medicinal herb, has been shown to exhibit oral therapeutic anti
      herpes simplex virus (HSV) activity in mice. We purified two major anti-HSV
      compounds, moronic acid and betulonic acid, from the herbal extract by extraction
      with ethyl acetate at pH 10 followed by chromatographic separations and examined
      their anti-HSV activity in vitro and in vivo. Moronic acid was quantitatively a
      major anti-HSV compound in the ethyl acetate-soluble fraction. The effective
      concentrations for 50% plaque reduction of moronic acid and betulonic acid for
      wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 microgram/ml, respectively. The
      therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic
      acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1,
      thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to moronic acid was
      similar to that of the wild-type HSV-1. When this compound was administered
      orally to mice infected cutaneously with HSV-1 three times daily, it
      significantly retarded the development of skin lesions and/or prolonged the mean
      survival times of infected mice without toxicity compared with the control.
      Moronic acid suppressed virus yields in the brain more efficiently than those in
      the skin. This was consistent with the prolongation of mean survival times. Thus,
      moronic acid was purified as a major anti-HSV compound from the herbal extract of
      Rhus javanica. Mode of the anti-HSV activity was different from that of ACV.
      Moronic acid showed oral therapeutic efficacy in HSV-infected mice and possessed
      novel anti-HSV activity that was consistent with that of the extract.

PMID- 10086990
TI  - Carrier-mediated lung distribution of HSR-903, a new quinolone antibacterial
      agent.
AB  - HSR-903 [(S)-(-)-5-amino-7-(7-amino-5-azaspiro[2. 4]hept-5-yl)-1-cyclopropyl-6
      fluoro-1, 4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid methanesulfonate]
      is a newly synthesized quinolone with a potent antibacterial activity and a low
      toxicity. The lung concentration of unchanged HSR-903 was about nine times higher
      than that in plasma after oral administration (5 mg/kg) in rats. In comparative
      studies, HSR-903 was accumulated more efficiently than levofloxacin,
      ciprofloxacin, and lomefloxacin in rat lung. To clarify the mechanism of the
      specific distribution of HSR-903 into the lung, the uptake of [14C]HSR-903 was
      studied using isolated rat lung cells and an isolated rat lung perfusion
      technique. Initial uptake of HSR-903 by isolated lung cells was temperature
      dependent, saturable, stereospecific, and Na+ and Cl- dependent. The Hill
      coefficients (1. 90 for Na+ and 1.13 for Cl-) suggest that two Na+ and one Cl-
      are associated with the transport of one HSR-903 molecule. The uptake of HSR-903
      was inhibited by other quinolone antibacterial agents, grepafloxacin, and
      sparfloxacin. The extraction ratio of HSR-903 in isolated lung perfusion was
      temperature dependent and saturable. These findings suggest that HSR-903 is taken
      up by the lung cells via a carrier-mediated transport mechanism, resulting in a
      concentrative distribution into the lung.

PMID- 10086991
TI  - Effects of LY295427, a low-density lipoprotein (LDL) receptor up-regulator, on
      LDL receptor gene transcription and cholesterol metabolism in normal and
      hypercholesterolemic hamsters.
AB  - The action of LY295427 [(3alpha,4alpha, 5alpha)-4-(2-propenylcholestan-3-ol)], a
      compound that derepresses low-density lipoprotein receptor (LDL-R) expression in
      a cell-based model, was examined in hamsters. It was found that the compound does
      not have an effect in normal chow-fed hamsters, in which LDL-R levels are not
      repressed, but exerts a marked hypocholesterolemic effect (>70% decrease) in
      cholesterol-coconut oil-fed hamsters, in which LDL-R is repressed. In this model,
      there is a dose-response for cholesterol lowering with an approximate ED50 value
      of 40 mg/kg/day and an inverse relationship between serum cholesterol and serum
      LY295427 levels. LDL-R mRNA is increased (2-fold) and liver cholesterol ester
      content is decreased (>90%). Unlike the 3-hydroxy-3-methylglutarylcoenzyme A
      reductase inhibitor lovastatin, the decreased serum cholesterol is confined to
      the non-high-density lipoprotein fraction. Furthermore, LY295427 does not affect
      cholesterol biosynthesis, and it does not have a significant effect on
      cholesterol absorption. These data suggest that LY295427 acts in the
      hypercholesterolemic hamster by derepressing LDL-R transcription, thereby
      enhancing cholesterol clearance from the blood. The results with LY295427 suggest
      that compounds that act to increase LDL-R may represent a novel approach in the
      pharmacotherapy for hypercholesterolemia.

PMID- 10086992
TI  - Pharmacokinetic analysis of the cardioprotective effect of 3-(2,2, 2
      trimethylhydrazinium) propionate in mice: inhibition of carnitine transport in
      kidney.
AB  - The site of action of 3-(2,2,2-trimethylhydrazinium) propionate (THP), a new
      cardioprotective agent, was investigated in mice and rats. I.p. administration of
      THP decreased the concentrations of free carnitine and long-chain acylcarnitine
      in heart tissue. In isolated myocytes, THP inhibited free carnitine transport
      with a Ki of 1340 microM, which is considerably higher than the observed serum
      concentration of THP. The major cause of the decreased free carnitine
      concentration in heart was found to be the decreased serum concentration of free
      carnitine that resulted from the increased renal clearance of carnitine by THP.
      The estimated Ki of THP for inhibiting the reabsorption of free carnitine in
      kidneys was 52.2 microM, which is consistent with the serum THP concentration
      range. No inhibition of THP on the carnitine palmitoyltransferase activity in
      isolated mitochondrial fractions was observed. These results indicate that the
      principal site of action of THP as a cardioprotective agent is the carnitine
      transport carrier in the kidney, but not the carrier in the heart.

PMID- 10086993
TI  - Role of antioxidant defenses against ethanol-induced damage in cultured rat
      gastric epithelial cells.
AB  - Reactive oxygen species appears to be involved in the pathogenesis of ethanol
      induced gastric mucosal injury in vivo. Because ingested ethanol diffuses into
      the gastric mucosa, targeting both epithelium and endothelium, in the present
      study we examined the possible protective effect of antioxidants on ethanol
      damage in gastric epithelial cells and endothelial cells in vitro. Cytotoxicity
      by ethanol was quantified by measuring 51Cr release. The effects of impairment of
      the glutathione redox cycle and of inhibition of cellular catalase were examined.
      The generation of superoxide was assessed by the reduction in cytochrome c.
      Ethanol caused a time- and dose-dependent increase in 51Cr release from
      epithelial cells. Incubation of cells with DL-buthionine-(S,R)-sulfoximine, while
      reducing glutathione production, dose dependently enhanced ethanol-induced
      injury. 1,3-Bis(chloroethyl)-nitrosourea, while inhibiting glutathione reductase
      activity, also sensitized cells to ethanol. In contrast, the inhibition of
      catalase with 3-amino-1,2, 4-triazole did not alter the susceptibility of
      epithelial cells to ethanol. Ethanol induced damage to endothelial cells in a
      similar fashion. In endothelial cells, however, neither impairment of the
      glutathione cycle nor inhibition of catalase influenced ethanol-induced damage.
      Epithelial cells, when exposed to ethanol, increased superoxide production as a
      function of ethanol concentration, whereas endothelial cells did not. The
      glutathione redox cycle, but not cellular catalase, plays a critical role in
      protecting epithelial cells against ethanol damage, whereas neither antioxidant
      seems to play a role in protection of endothelial cells. The distinct difference
      in antioxidant protection against ethanol appears to depend on the capability of
      each cell to produce cytotoxic oxygen species in response to ethanol exposure.

PMID- 10086994
TI  - Behavioral and neurochemical effects of the dopamine transporter ligand 4
      chlorobenztropine alone and in combination with cocaine in vivo.
AB  - The current studies evaluated the novel diphenylmethoxytropane analog 4
      chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for
      their abilities to stimulate locomotor activity, produce cocaine-like
      discriminative stimulus effects, and elevate extracellular dopamine (DA) in the
      nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally
      administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a
      locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl
      BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative
      stimulus effects in rats trained to discriminate i.p. injections of 10 mg/kg
      cocaine from saline. The time course of behavioral activation differed markedly
      between the two drugs, with much shorter onset and duration of locomotor
      stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10
      and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the
      NAc, whereas i.p. 4-Cl-BZT was effective only at the higher dose and produced a
      more gradual, modest, and sustained (>/=2 h) elevation in accumbens DA. In
      contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 microM) into
      the NAc through the microdialysis probe elevated extracellular DA to a much
      greater extent than did local cocaine (nearly 2000% of baseline maximally for 4
      Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration
      of action than cocaine. However, when microinjected bilaterally into the NAc at
      30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulant than
      4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the
      locomotor stimulant, discriminative stimulus effects, and NAc DA response to a
      subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog
      also facilitated the emergence of stereotyped behavior and convulsions induced by
      high-dose cocaine. The current results demonstrate that DA transporter ligands
      that do not share the neurochemical and behavioral profiles of cocaine
      nevertheless may enhance the effects of cocaine in vivo.

PMID- 10086995
TI  - Tretinoin prevents age-related renal changes and stimulates antioxidant defenses
      in cultured renal mesangial cells.
AB  - Age-related progressive glomerular sclerosis in the rat is associated with
      increased expression of tumor necrosis factor-beta1 and increased protein content
      in the renal cortex, enhanced production of H2O2, in both renal glomeruli and
      mesangial cells (MCs) cultured from them, as well as augmented glomerular
      oxidative damage. We have previously shown that tretinoin-treated old male
      Fischer 344 rats have 30% lower protein content in the renal cortex than control
      old rats. Here, we report that this effect may depend on the inhibition of the
      expression of tumor necrosis factor-beta1, a matrigenic cytokine, and
      osteopontin, a protein with cell adhesive and chemotactic properties. In
      addition, we show that tretinoin prevents the cytotoxicity of H2O2 in cultured
      human MCs by increasing both the catalase activity and the reduced glutathione
      content, which are dose- and time-dependent changes. These increases were not
      dependent on each other: when these effects were previously inhibited with 3
      amino-1,2,4-atriazole or L-buthionine-(S, R)-sulfoximine, respectively, tretinoin
      still induced the increase of the other noninhibited antioxidant defense. An
      enhanced gene transcription is the most likely mechanism involved in the
      tretinoin-induced stimulation of MC antioxidant defense systems because 1)
      preincubation of MCs with actinomycin D or cycloheximide fully abolished it; 2)
      tretinoin-incubated MCs showed increased levels of catalase mRNA and gamma
      glutamyl-cysteine synthetase (catalytic subunit) mRNA, the latter being the rate
      limiting step in de novo reduced glutathione synthesis; and 3) the stability of
      both mRNA was unchanged by tretinoin. These results show one strategy of
      protecting renal cells from H2O2-mediated injury based on increasing their
      antioxidant defenses.

PMID- 10086996
TI  - Local alpha-bungarotoxin-sensitive nicotinic receptors modulate hippocampal
      norepinephrine release by systemic nicotine.
AB  - Previous studies have shown that nicotinic receptors (NAChRs) accessible from the
      cerebral aqueduct of the brainstem mediate the hippocampal norepinephrine (NE)
      release induced by i.v. nicotine. The present study was designed to investigate
      the role of hippocampal NAChRs in this process. Nicotinic antagonists were
      microinjected or microdialyzed into the hippocampus (HP) before administering
      nicotine (0.09 mg/kg over 60 s, i.v.) to freely moving rats. alpha-Bungarotoxin
      (0.3 nmol by microinjection) blocked nicotine-induced hippocampal NE release by
      47% (p <.05) and abolished the effect of 0.065 mg/kg nicotine. Methyllycaconitine
      (1.4-5.6 mM in the dialysate) inhibited the stimulatory effect of nicotine 0.09
      mg/kg by 48 to 75% (p <.05). In contrast, mecamylamine (2.9-5.8 mM) and dihydro
      beta-erythroidine (7-14 mM) were completely ineffective. The role of hippocampal
      NAChRs was demonstrated further by selectively desensitizing these receptors
      before the systemic infusion of nicotine. To do so, the HP was pretreated with
      nicotine (0.1 mM) delivered through the microdialysis probe; this concentration
      was calculated to yield tissue concentrations similar to those produced by the
      systemic infusions of nicotine. Dialyzing this concentration of nicotine into the
      HP inhibited the NE response to i.v. nicotine by 34% (p <.05), and 1.0 mM
      nicotine reduced the response by 40%. These studies indicate that alpha
      bungarotoxin-sensitive hippocampal NAChRs, probably containing alpha7 subunits,
      modulate hippocampal NE release because of systemic nicotine.

PMID- 10086997
TI  - Prostaglandin E-prostanoid-3 receptor activation of cyclic AMP response element
      mediated gene transcription.
AB  - The prostaglandin E-prostanoid (EP)3 receptor signals primarily through the
      inhibitory G protein Gi, thereby decreasing intracellular cAMP levels. To study
      the signal transduction properties of the rabbit EP3 receptor, five splice
      variants were expressed in HEK293tsA201 cells: 72A, 74A, 77A, 80A and the novel
      splice variant NT, which lacks the C-terminal sequence. The ability of the EP3
      receptor splice variants to modulate expression of a beta-galactosidase reporter
      gene under the control of a promoter containing cAMP response elements (CRE) was
      assessed. Each splice variant induced sulprostone-mediated increase in beta
      galactosidase enzymatic activity with EC50 ranging from 0.8 nM for the NT splice
      variant to 3.1 nM for the 77A splice variant. Substitution of either Asp338 with
      Ala, or Arg329 with Ala or Glu in the 77A splice variant resulted in a loss of
      receptor-evoked increases in beta-galactosidase activity, whereas substitution of
      Lys300 with alanine had no effect on signal transduction. These phenotypes
      correlate with the inhibition of cAMP generation by direct cAMP measurement.
      Signal transduction was insensitive to pretreatment of cells with pertussis
      toxin, suggesting that a nonGi/Go pathway is activated by the EP3 receptor.
      Direct measurement of second messenger levels confirmed that there was no
      increase in cAMP levels mediated by the 77A splice variant, however, there was a
      modest increase in intracellular Ca2+. Partial blockade of the reporter activity
      with kinase inhibitors demonstrates that CRE activation is mediated in part by a
      Ca2+-dependent kinase pathway. These data suggest that the EP3 receptor signals
      through a novel cAMP response element binding protein/CRE pathway.

PMID- 10086998
TI  - Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and
      Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds.
AB  - Effects of cytochrome P-450 3A- and P-glycoprotein (P-gp)-related compounds,
      erythromycin, midazolam, ketoconazole, verapamil, and quinidine, on transport of
      rhodamine 123 (Rho-123), a P-gp substrate, were studied in rat intestine and in
      Caco-2 cells. Ileum was mainly used in rat studies because this segment showed
      greater P-gp-mediated Rho-123 transport. In an in vitro everted rat ileum, all
      the compounds examined significantly inhibited the transport of Rho-123 from
      serosal to mucosal surfaces across the intestine, with different inhibitory
      potencies among these compounds. In an in vivo rat study, the exsorption of Rho
      123 from blood to the intestinal lumen, which was evaluated as exsorption
      clearance of Rho-123 under a steady-state plasma concentration of Rho-123, was
      also inhibited when these compounds were added to the intestinal lumen.
      Similarly, transepithelial transport of Rho-123 from the basolateral to apical
      side across Caco-2 cell monolayers was inhibited by these compounds. A linear
      relationship was observed in their inhibitory potencies on Rho-123 transport
      between in vitro and in vivo studies using rat ileum and between studies with rat
      ileum and Caco-2 cells. P-gp-mediated transport across the intestine was found to
      be inhibited not only by P-gp-related but also by all the cytochrome P-450 3A
      related compounds examined. Within experimental error, the relative inhibitory
      potencies were the same between the studies with rat ileum (in vivo, in vitro)
      and those with Caco-2 cells. Thus, it is suggested that the function of P-gp and
      its sensitivity to these drugs may be similar in rat intestine and Caco-2 cells.

PMID- 10086999
TI  - Electrophysiologic effects of chronic amiodarone therapy and hypothyroidism,
      alone and in combination, on guinea pig ventricular myocytes.
AB  - Amiodarone is a widely used antiarrhythmic drug, the mechanisms of action of
      which remain incompletely understood. Indirect evidence suggests that the class
      III properties of amiodarone may be mediated by cardiac antithyroid effects. We
      sought to determine whether the effects of chronic amiodarone on repolarization
      in guinea pig hearts can be attributed to an antithyroid action by studying the
      changes in dofetilide-sensitive rapid (IKr) and dofetilide-resistant slow (IKs)
      delayed rectifier currents, inward rectifier K+ current (IK1), and action
      potentials of ventricular myocytes from five groups of guinea pigs: control,
      hypothyroid, amiodarone-treated for 7 days, hypothyroid plus amiodarone, and
      vehicle (dimethyl sulfoxide) treated. IKs was reduced by amiodarone (to 61% of
      control, P <.05, at 50 mV) but was more strongly reduced by hypothyroidism (to
      35% of control, P <.01, 50 mV). Amiodarone significantly reduced IKr and IK1 (by
      55 and 64% at 10 mV and -50 mV, respectively), which were unaffected by
      hypothyroidism. Amiodarone alone and hypothyroidism alone had similar action
      potential-prolonging actions. Hypothyroid animals treated with amiodarone showed
      a combination of ionic effects (strong IKs reduction, similar to hypothyroidism
      alone; reduced IKr and IK1, similar to amiodarone alone), along with action
      potential prolongation significantly greater than that caused by either
      intervention alone. We conclude that chronic amiodarone and hypothyroidism have
      different effects on ionic currents and that their combination prolongs action
      potential duration to a greater extent than either alone in guinea pig hearts,
      suggesting that the class III actions of amiodarone are not mediated by a cardiac
      hypothyroid state.

PMID- 10087000
TI  - Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and
      chronic inflammation.
AB  - The marine product petrosaspongiolide M is a novel inhibitor of phospholipase A2
      (PLA2), showing selectivity for secretory PLA2 versus cytosolic PLA2, with a
      potency on the human synovial enzyme (group II) similar to that of manoalide.
      This compound was more potent than manoalide on bee venom PLA2 (group III) and
      had no effect on group I enzymes (Naja naja and porcine pancreatic PLA2).
      Inhibition of PLA2 was also observed in vivo in the zymosan-injected rat air
      pouch, on the secretory enzyme accumulated in the pouch exudate.
      Petrosaspongiolide M decreased carrageenan paw edema in mice after the oral
      administration of 5, 10, or 20 mg/kg. This marine metabolite (0.01-1.0
      micromol/pouch) induced a dose-dependent reduction in the levels of prostaglandin
      (PG)E2, leukotriene B4, and tumor necrosis factor-alpha in the mouse air pouch
      injected with zymosan 4 h after the stimulus. It also had a weaker effect on cell
      migration. The inflammatory response of adjuvant arthritis was reduced by
      petrosaspongiolide M, which also inhibited leukotriene B4 levels in serum and
      PGE2 levels in paw homogenates. In contrast with indomethacin, this marine
      compound did not reduce PGE2 levels in stomach homogenates. Petrosaspongiolide M
      is a new inhibitor of secretory PLA2 in vitro and in vivo, with anti-inflammatory
      properties in acute and chronic inflammation.

PMID- 10087001
TI  - Central administration of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)-NH2 and orphanin
      FQ/nociceptin (OFQ/N) produce similar cardiovascular and renal responses in
      conscious rats.
AB  - In vitro studies have shown that [Phe1Psi(CH2-NH)Gly2]OFQ/N(1-13)-NH2 (referred
      to as [FG]OFQ/N(1-13)-NH2) is the first selective antagonist to prevent the
      binding of the endogenous ligand orphanin FQ/Nociceptin (OFQ/N) at the orphan
      opioid-like receptor. In the present study, we examined the potential changes in
      cardiovascular and renal function produced by the i.c.v. injection of [FG]OFQ/N(1
      13)-NH2 in conscious Sprague-Dawley rats. In conscious rats, i.c.v. injection of
      [FG]OFQ/N(1-13)-NH2 produced a marked and sustained decrease in heart rate, mean
      arterial pressure, and urinary sodium excretion and a profound increase in urine
      flow rate (i.e., a water diuresis). The cardiovascular and renal excretory
      responses produced by i.c.v. [FG]OFQ/N(1-13)-NH2 were dose dependent and were
      similar in pattern but of longer duration than responses evoked by i.c.v. OFQ/N.
      In other animals, the i.c.v. injection of OFQ/N(1-13)-NH2, a potential metabolite
      of [FG]OFQ/N(1-13)-NH2, produced changes in cardiovascular and renal function
      that were comparable to those evoked by i.c.v. [FG]OFQ/N(1-13)-NH2. In contrast,
      OFQ/N(2-17), a fragment of OFQ/N [OFQ/N(1-17)], was inactive when administered
      centrally. Finally, studies were performed to determine whether [FG]OFQ/N(1-13)
      NH2 may be an antagonist at the orphan opioid-like receptor receptor when
      administered centrally at a dose that alone was inactive. In these studies,
      i.c.v. pretreatment of animals with low-dose [FG]OFQ/N(1-13)-NH2 failed to
      prevent the cardiovascular and renal excretory response to i.c.v. OFQ/N. Although
      [FG]OFQ/N(1-13)-NH2 is reported to be an antagonist of the OFQ/N receptor in
      vitro, these findings indicate that this compound has agonist activity similar to
      that of the endogenous ligand OFQ/N when administered centrally in vivo.

PMID- 10087002
TI  - Effects of BAY 10-6734 (Embusartan), a new angiotensin II type I receptor
      antagonist, on vascular smooth muscle cell growth.
AB  - Angiotensin II (AII), an important hypertrophic factor in the cardiovascular
      system, exerts most of its known effects in vivo through the AII receptor type 1
      (AT1) subclass of AII receptors. These receptors are also responsible for the
      growth-related effects of AII in cultured vascular smooth muscle cells (VSMCs).
      We presently investigated the effects of BAY 10-6734 (Embusartan), a new orally
      active AT1 antagonist, on VSMC growth and proliferation of cultured VSMCs
      isolated from the aortae of Wistar Kyoto rats and spontaneously hypertensive
      rats. BAY 10-6734 and losartan (considered as AT1 receptor antagonist of
      reference), as well as their respective active metabolites, were studied for
      their inhibition of: 1) [125I]AII binding to its receptors, 2) AII-induced DNA
      and protein synthesis (by measuring the incorporation of 5-bromo-2'-deoxyuridine
      and [3H]L-leucine, respectively), and 3) AII-induced variations in intracellular
      Ca2+ concentration, using cells labeled with Fura-2. All of the tested compounds
      inhibited the aforementioned parameters in a concentration-dependent manner. Half
      maximal inhibitory concentration values indicated that BAY 10-6734 was
      significantly more potent than losartan and that spontaneously hypertensive rat
      derived VSMCs were more sensitive than Wistar Kyoto rat-derived ones. Neither BAY
      10-6734 nor losartan affected the intracellular Ca2+ concentration of
      unstimulated VSMCs but both compounds inhibited both AII-induced Ca2+
      mobilization from internal stores and Ca2+ influx. Neither compound affected
      arginine-vasopressin-, basic fibroblast growth factor-, or serum-induced DNA and
      protein synthesis. BAY 10-6734 appears therefore as a potent and specific new
      inhibitor of AII-induced growth-related events in VSMCs.

PMID- 10087003
TI  - Pharmacological characterization of protein phosphatase activities in
      preparations from failing human hearts.
AB  - beta-Adrenoceptor stimulation acts in the heart in part by increasing the
      phosphorylation state of phospholamban and phospholemman. There is evidence that
      the beta-adrenoceptor-mediated increase in phospholamban phosphorylation is in
      part due to inhibition of type 1 phosphatases. The aim of the present study was
      to elucidate which phosphatases dephosphorylate phospholamban and phospholemman
      in the human heart. In the past, cardiac serine/threonine phosphatases have been
      studied using phosphorylase a as substrate. Here, type 1 and type 2A phosphatase
      activities were studied in preparations from failing human hearts using
      phosphorylated phospholamban and phospholemman as substrates. Phospholamban and
      phospholemman phosphatase activity was detectable in human cardiac homogenates.
      Moreover, using a heparin-Sepharose column, the catalytic subunits of type 1 and
      type 2A phosphatases could be separated from human ventricles. Okadaic acid and
      cantharidin inhibited phosphatase activities dephosphorylating phospholamban,
      phospholemman, and phosphorylase a in homogenates in a concentration-dependent
      manner. However, okadaic acid was more potent. Cantharidin inhibited type 2A and
      type 1 activities against all substrates studied with IC50 values <15 nM and >290
      nM, respectively. Okadaic acid inhibited type 1 and type 2A phosphatase
      activities as effectively but 10-30 times more potently than cantharidin. This
      work provides evidence that in the human heart, type 1 and 2A phosphatases are
      involved in the dephosphorylation of phospholamban and phospholemman and could
      play a role in the effects of beta-adrenergic stimulation in the heart.

PMID- 10087004
TI  - Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats
      with ascites and water retention.
AB  - kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone
      (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in
      cirrhosis; however, there is no information concerning the effects induced by the
      chronic administration of these drugs under this condition. To compare the renal
      and hormonal effects induced by the long-term oral administration of niravoline,
      OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and
      urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions
      and for 10 days after the daily oral administration of niravoline, OPC-31260, or
      vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance,
      serum osmolality, ADH mRNA expression, and systemic hemodynamics were also
      measured at the end of the study. Niravoline increased water excretion,
      peripheral resistance, serum osmolality, and sodium excretion and reduced
      creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC
      31260 also increased water metabolism and sodium excretion and reduced urinary
      ALD, although the aquaretic effect was only evident during the first 2 days, and
      no effects on serum osmolality, renal filtration, and systemic hemodynamics were
      observed. Therefore, both agents have aquaretic efficacy, but the beneficial
      therapeutic effects of the long-term oral administration of niravoline are more
      consistent than those of OPC-31260 in cirrhotic rats with ascites and water
      retention.

PMID- 10087005
TI  - Both the antioxidant and D3 agonist actions of pramipexole mediate its
      neuroprotective actions in mesencephalic cultures.
AB  - Pramipexole (PPX) is a full intrinsic activity, direct-acting dopamine (DA)
      agonist possessing 7-fold higher affinity for D3 than for D2 receptors. It also
      is a potent antioxidant. PPX was previously shown to be neuroprotective because
      it dose dependently attenuated the DA neuron loss produced by levodopa in
      mesencephalic cultures. Several different drugs with properties similar to PPX
      were studied here to better understand the mechanism or mechanisms responsible
      for this neuroprotective effect. The D3-preferring agonist 7-hydroxy
      diphenylaminotetralin (7-OH-DPAT) and the D3 antagonist U99194, respectively,
      increased and decreased the neuroprotective effects of PPX in a dose-dependent
      fashion. Addition of the selective D2 agonist U95666 or the D2/D3 antagonists
      domperidone or raclopride did not affect PPX's neuroprotective effect.
      Interestingly, 7-OH-DPAT by itself did not attenuate the DA neuron loss produced
      by levodopa. However, when 7-OH-DPAT was combined with a low dose of the
      antioxidants U101033E or alpha-tocopherol, the toxic effects of levodopa were
      attenuated. Similar results were observed when the D3-preferring agonist PD128,
      907 was studied. In addition, media conditioned by exposure of mesencephalic
      cultures incubated with all D3-preferring agonists studied was shown to enhance
      the growth of DA neurons in freshly harvested recipient cultures implicating a D3
      mediated trophic activity in the neuroprotective effect. These data suggest that
      PPX's neuroprotective actions in the levodopa toxicity model are a consequence of
      its combined actions as a D3 receptor agonist and an antioxidant.

PMID- 10087006
TI  - Effects of pirfenidone on procollagen gene expression at the transcriptional
      level in bleomycin hamster model of lung fibrosis.
AB  - A time course study was carried out to elucidate the mechanisms for antifibrotic
      effect of pirfenidone (PD). Hamsters were intratracheally (i.t.) instilled with
      saline (SA) or bleomycin (BL) (7.5 units/kg/5 ml). The animals were fed a diet
      containing 0.5% PD or the same control diet (CD) without the drug 2 days before
      and throughout the study. The animals were sacrificed at various times after
      instillation. The lung hydroxyproline level in BL + CD groups was gradually
      increased and peaked at 21 days to 181% of the SA + CD control. The BL + PD
      treated groups showed a gradual decrease in their lung collagen content, showing
      a maximum reduction of 40% at day 21. The lung malondialdehyde levels of the BL +
      CD groups were increased by several-fold of the corresponding SA + CD groups at
      various times. The lung prolyl hydroxylase (PH) activities in the BL + CD groups
      were also increased by several-fold of the corresponding SA + CD groups at these
      time points. The hamsters in the BL + PD showed a gradual decrease in the lung
      malondialdehyde levels from 10 to 21days compared with their corresponding BL +
      CD groups. Treatment with PD also reduced the lung PH activities in the BL + PD
      groups compared with the corresponding BL + CD groups. However, PD failed to
      manifest any direct inhibitory effect on PH activity in vitro. BL treatment
      increased the lung procollagen I and III gene expressions in the BL + CD groups
      by several-fold at varying times compared with the corresponding SA + CD, and
      treatment with PD in the BL + PD groups significantly down-regulated the BL
      induced overexpression of these genes. Studies evaluating the regulation of these
      genes at the transcriptional level revealed PD significantly reduced the
      transcription of PC I at 14 days. Our results indicate that the antifibrotic
      effect of PD was partly due to suppression of the BL-induced inflammatory events
      and partly due to down-regulation of BL-induced overexpression of lung
      procollagen I and III genes.

PMID- 10087007
TI  - Orexin A but not orexin B rapidly enters brain from blood by simple diffusion.
AB  - We determined the ability of orexin A and orexin B, recently discovered
      endogenous appetite enhancers, to cross the blood-brain barrier (BBB) of mice.
      Multiple time-regression analysis showed that an i.v. bolus of 125I-orexin A
      rapidly entered the brain from the blood, with an influx rate (Ki = 2.5 +/- 0.3 x
      10(-4) ml/g.min) many times faster than that of the 99mTc-albumin control. This
      relatively rapid rate of entry was not reduced by administration of excess orexin
      A (or leptin) or by fasting for 22 h, even when penetration into only the
      hypothalamus was measured. Lack of saturability also was shown by perfusion in
      blood-free buffer. HPLC revealed that most of the injected 125I-orexin A reached
      the brain as intact peptide. Capillary depletion studies showed that the
      administered peptide did not remain bound to the endothelial cells comprising the
      BBB but reached the brain parenchyma. Efflux of 125I-orexin A from the brain
      occurred at the same rate as 99mTc-albumin. The octanol/buffer partition
      coefficient of 0.232 showed that orexin A was highly lipophilic, whereas the
      value for orexin B was only 0.030. Orexin B, moreover, was rapidly degraded in
      blood, so no 125I-orexin B could be detected in intact form in brain when
      injected peripherally. Thus, although orexin B is rapidly metabolized in blood
      and has low lipophilicity, orexin A rapidly crosses the BBB from blood to reach
      brain tissue by the process of simple diffusion.

PMID- 10087008
TI  - Decreased tissue distribution of L-carnitine in juvenile visceral steatosis mice.
AB  - We kinetically analyzed the disposition of L-carnitine of juvenile visceral
      steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism
      of the systemic L-carnitine deficiency of JVS mice. There were significant
      differences in the plasma concentration-time course of total radioactive
      carnitine (L-[3H]carnitine, [acetyl-3H]carnitine, and other [acyl-3H]carnitines)
      between normal and JVS mice after a single i.v. or p.o. administration of L
      [3H]carnitine (250 ng/kg). The oral bioavailability of L-[3H]carnitine in JVS
      mice (0.341) was about half of that in normal mice (0.675). The cumulative
      urinary excretion of total radioactive carnitine in JVS mice was about 10-fold
      more than that in normal mice, and the total clearance of unchanged L
      [3H]carnitine for JVS mice (6.70 ml/min) was significantly higher than that for
      normal mice (2.45 ml/min). The distribution volume at the steady state of
      unchanged L-[3H]carnitine in JVS mice (1.10 liters/kg) was significantly smaller
      than that in normal mice (8.16 liters/kg). At 4 h after an i.v. administration,
      the apparent tissue-to-plasma concentration ratios of unchanged L-[3H]carnitine
      for various tissues of JVS mice, except for brain, were about one half to one
      20th of those in normal mice. In conclusion, this in vivo disposition kinetic
      study of L-carnitine supports the previous in vitro finding that the L-carnitine
      transporter is absent or functionally deficient in JVS mice because the renal
      reabsorption, the intestinal absorption, and the apparent tissue-to-plasma
      concentration ratios in JVS mice are significantly lower than those in normal
      mice. The JVS mouse should be a useful experimental model for studying carnitine
      deficiency diseases.

PMID- 10087009
TI  - Relationship between circadian rhythm of vinorelbine toxicity and efficacy in
      P388-bearing mice.
AB  - The relevance of chronopharmacology for improving tolerability and antitumor
      efficacy of the antimitotic drug vinorelbine was investigated in female B6D2F1
      mice standardized with 12 h of light and 12 h of darkness. A single i.v.
      vinorelbine dose (26 mg/kg) was given to 279 mice at 7, 11, 19, or 23 hours after
      light onset (HALO). Bone marrow necrosis and leukopenia were nearly twice as
      large in the mice injected at 7 HALO as compared with those treated at 19 HALO
      (ANOVA: p <.001 and p = 0.004, respectively). The relevance of vinorelbine dosing
      time for antitumor efficacy was assessed in 672 P388 leukemia-bearing mice.
      Vinorelbine was injected as a single dose (20, 24, 26, or 30 mg/kg) or weekly
      (20, 24, 26, or 28 mg/kg/injection x 3) at one of six circadian times, 4 h apart.
      A significant correlation between single dose and median survival time was
      limited to vinorelbine administration at 19 or 23 HALO. An increase in the
      vinorelbine weekly dose shortened median survival time in the mice treated at 7
      HALO (20 mg/kg: 29 days; 24 mg/kg: 17 days; and 26 mg/kg: 6 days) but
      significantly improved it in those treated at 19 HALO (20 mg/kg: 28.5 days; 24
      mg/kg: 32 days; and 26 mg/kg: 36 days). The study demonstrates the circadian
      rhythm dependence of maximum tolerated dose and the need to deliver maximum
      tolerated dose at the least toxic time to achieve survival improvement through
      chronotherapy. This may be obtained with an evening administration of vinorelbine
      in cancer patients.

PMID- 10087010
TI  - RSD1000: a novel antiarrhythmic agent with increased potency under acidic and
      high-potassium conditions.
AB  - This study reports the use of a novel agent, RSD1000 [(+/-)-trans-[2-(4
      morpholinyl)cyclohexyl]naphthalene-1-acetate mono hydrochloride], to test the
      hypothesis that a drug with pKa close to the pH found in ischemic tissue may have
      selective antiarrhythmic actions against ischemia-induced arrhythmias. The
      antiarrhythmic ED50 for RSD1000 against ischemic arrhythmias was 2.5 +/- 0.1
      micromol/kg/min in rats. This value was significantly lower than doses that
      suppressed electrically induced arrhythmias. In isolated rat hearts, RSD1000 was
      approximately 40 times more potent in producing ECG changes (i.e., P-R and QRS
      prolongation) in acid (pHo = 6.4) and high [K+]o (10.8 mM) buffer than in normal
      buffer (pHo = 7.4; [K+]o = 3.4 mM). In patch-clamped, whole-cell rat cardiac
      myocytes, inhibition of sodium (INa) currents by RSD1000 was pH- and use
      dependent. The IC50 for INa blockade was lower (P <.05) in acid (0.8 +/- 0.1
      microM) than in pH 7.3 (2.9 +/- 0.3 microM), respectively, whereas the IC50 for
      blockade of transient outward potassium current (ITO) at pH = 6.4 and 7.3 was 3.3
      +/- 0.4 and 2.8 +/- 0.1 microM, respectively. Mixed ion channel block in ischemic
      myocardium with minimal effects on normal cardiac tissue, as governed by the low
      pKa of RSD1000, may account for its antiarrhythmic activity against ischemia
      induced arrhythmias.

PMID- 10087011
TI  - A role for N-arachidonylethanolamine (anandamide) as the mediator of sensory
      nerve-dependent Ca2+-induced relaxation.
AB  - We tested the hypothesis that an endogenous cannabinoid (CB) receptor agonist,
      such as N-arachidonylethanolamine (anandamide), is the transmitter that mediates
      perivascular sensory nerve-dependent Ca2+-induced relaxation. Rat mesenteric
      branch arteries were studied using wire myography; relaxation was determined
      after inducing contraction with norepinephrine. Cumulative addition of Ca2+
      caused dose-dependent relaxation (ED50 = 2.2 +/- 0.09 mM). The relaxation was
      inhibited by 10 mM TEA and 100 nM iberiotoxin, a blocker of large conductance
      Ca2+-activated K+ channels, but not by 5 microM glibenclamide, 1 mM 4
      aminopyridine, or 30 nM apamin. Ca2+-induced relaxation was also blocked by the
      selective CB receptor antagonist SR141716A and was enhanced by pretreatment with
      4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (pefabloc; 30 microM), an
      inhibitor of anandamide metabolism. Anandamide also caused dose-dependent
      relaxation (ED50 =.72 +/- 0.3 microM). The relaxation was not inhibited by
      endothelial denudation, 10 microM indomethacin, or 1 microM miconazole, but was
      blocked by 3 microM SR141716A, 10 mM TEA, precontraction with 100 mM K+, and 100
      nM iberiotoxin, and was enhanced by treatment with 30 microM pefabloc. Mesenteric
      branch arteries were 200-fold more sensitive to the relaxing action of anandamide
      than arachidonic acid (ED50 = 160 +/- 7 microM). These data show that: 1) Ca2+
      and anandamide cause hyperpolarization-mediated relaxation of mesenteric branch
      arteries, which is dependent on an iberiotoxin-sensitive Ca2+-activated K+
      channel, 2) relaxation induced by both Ca2+ and anandamide is inhibited by CB
      receptor blockade, and 3) relaxation induced by anandamide is not dependent on
      its breakdown to arachidonic acid and subsequent metabolism. These findings
      support the hypothesis that anandamide, or a similar cannabinoid receptor
      agonist, mediates nerve-dependent Ca2+-induced relaxation in the rat.

PMID- 10087012
TI  - Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat
      human T lymphocyte cell line.
AB  - The sigma binding site present in the Jurkat human T lymphocyte cell line was
      investigated. Jurkat cell membranes were found to have a single saturable binding
      site for [3H]haloperidol, a sigma ligand (dissociation constant, 3.9 +/- 0.3 nM).
      The binding of [3H]haloperidol was inhibited by several sigma ligands. Northern
      analysis and reverse transcription-polymerase chain reaction provided evidence
      for the expression of the recently cloned type 1 sigma-receptor (sigma-R1) in
      Jurkat cells. The sigma-R1 cDNA cloned from these cells was functional in
      heterologous expression systems. When expressed in mammalian cells, the cDNA
      induced binding was saturable with dissociation constants of 1.9 +/- 0.3 nM for
      [3H]haloperidol and 12 +/- 2 nM for (+)-pentazocine. The binding of
      [3H]progesterone, a putative endogenous ligand to sigma-R1, to the Jurkat cell
      sigma-receptor could be directly demonstrated by using heterologously expressed
      sigma-R1 cDNA. The binding of [3H]progesterone was saturable, with a dissociation
      constant of 88 +/- 7 nM. Progesterone and haloperidol interacted with the
      receptor competitively. Reverse transcription-polymerase chain reaction also
      produced evidence for the existence of an alternatively spliced sigma-R1 variant
      in Jurkat cells. This splice variant was found to be nonfunctional in ligand
      binding assays. This constitutes the first report on the molecular
      characterization of the sigma-receptor in immune cells.

PMID- 10087013
TI  - Human endothelin-1 clearance kinetics revealed by a radiotracer technique.
AB  - Levels of endothelin-1 (ET-1) are elevated in many disease states, although its
      total body kinetics of elimination are poorly understood. Therefore, it remains
      uncertain whether the presence of elevated levels of ET-1 in the setting of
      disease are secondary to changes in production or clearance or some combination
      thereof. Using a 125I-labeled ET-1 infusion technique, the volume of distribution
      and kinetics of clearance of endothelin were described in five normal volunteers.
      Heart rate, blood pressure, right atrial pressure, and arterial blood samples for
      the counting of 125I and the measurement of ET-1 were obtained at multiple time
      points before and up to 45 h after the start of the infusion. The radiotracer
      infusion had no effect on heart rate, blood pressure, right atrial pressure, or
      endogenous ET-1 levels. ET-1 clearance was best described by a three-compartment
      model, which revealed that ET-1 has a much longer terminal half-life and volume
      of distribution than was previously reported. This suggests extensive uptake of
      ET-1 in various organ systems and slow clearance. These new findings have
      important implications for the understanding of the pathophysiology of ET-1 in
      disease states as well as for the understanding and development of ET-1 receptor
      blockers and endothelin-converting enzyme inhibitors.

PMID- 10087014
TI  - In vivo dopamine clearance rate in rat striatum: regulation by extracellular
      dopamine concentration and dopamine transporter inhibitors.
AB  - Dopamine transporter (DAT) inhibitors are expected to decrease dopamine (DA)
      clearance from the extracellular space of the brain. However, mazindol and
      cocaine have been reported to "anomalously" increase DA clearance rate. To better
      understand in vivo DAT activity both in the absence and presence of DAT
      inhibitors, clearance of exogenously applied DA was measured in dorsal striata of
      urethane-anesthetized rats using high-speed chronoamperometry. As higher amounts
      of DA were ejected, DA signal amplitudes, but not time courses, increased.
      Clearance rates increased until near maximal rates of 0.3 to 0.5 microM/s were
      attained. Provided baseline clearance rates were relatively low (< 0.1 microM/s),
      local application of either nomifensine or cocaine markedly increased exogenous
      DA signal amplitudes and time courses. Relative to the low baseline group,
      locally applied nomifensine decreased clearance rate when baseline clearance was
      high ( approximately 0.4 microM/s). However, even when baseline clearance rates
      were high, systemic injection of nomifensine, mazindol, GBR 12909, or benztropine
      increased DA signal amplitudes to a greater extent than time courses, consistent
      with the observed increases in clearance rates. In contrast, despite low baseline
      clearance rates, systemic injection of cocaine, WIN 35,428, or d-amphetamine
      preferentially increased DA signal time course, consistent with the observed
      decreases in clearance rates. Our results emphasize that as extracellular DA
      concentrations increase, DAT velocity increases to a maximum, partially
      explaining the ability of DAT inhibitors to increase DA clearance rates. However,
      by itself, kinetic activation is not sufficient to explain the ability of certain
      systemically administered DAT inhibitors to anomalously increase DA clearance.

PMID- 10087015
TI  - Modulation of amphetamine-stimulated [3H]dopamine release from rat
      pheochromocytoma (PC12) cells by sigma type 2 receptors.
AB  - An important regulatory mechanism of synaptic dopamine (DA) levels is activation
      of the dopamine transporter (DAT), which is a target for many drugs of abuse,
      including amphetamine (AMPH). sigma receptors are located in dopaminergic brain
      areas critical to reinforcement. We found previously that agonists at sigma2
      receptors enhanced the AMPH-stimulated release of [3H]DA from slices of rat
      caudate-putamen. In the present study, we modeled this response in
      undifferentiated pheochromocytoma-12 (PC12) cells, which contain both the DAT and
      sigma2 receptors but not neural networks that can complicate investigation of
      individual neuronal mechanisms. We found that enhancement of AMPH-stimulated
      [3H]DA release by the sigma agonist (+)-pentazocine was blocked by sigma2
      receptor antagonists. Additionally, the reduction in the effect of (+)
      pentazocine by the inclusion of ethylene glycol bis(beta-aminoethyl ether)
      N,N,N', N'-tetraacetic acid led us to hypothesize that sigma2 receptor activation
      initiated a Ca2+-dependent process that resulted in enhancing the outward flow of
      DA via the DAT. The source of Ca2+ required for the enhancement of reverse
      transport did not appear to be via N- or L-type voltage-dependent Ca2+ channels,
      because it was not affected by nitrendipine or omega-conotoxin. However, two
      inhibitors of Ca2+/calmodulin-dependent protein kinase II blocked enhancement in
      AMPH-stimulated release by (+)-pentazocine. Our findings suggest that sigma2
      receptors are coupled to the DAT via a Ca2+/calmodulin-dependent protein kinase
      II transduction system in PC12 cells, and that sigma2 receptor antagonists might
      be useful in the treatment of drug abuse by blocking elevation of DA levels via
      reversal of the DAT.

PMID- 10087016
TI  - Caffeine withdrawal: a parametric analysis of caffeine dosing conditions.
AB  - Although caffeine is the most widely used behaviorally active drug in the world,
      caffeine physical dependence has been only moderately well characterized in
      humans. Four double-blind experiments were conducted in independent groups of
      healthy participants to assess the conditions under which withdrawal symptoms
      occur upon cessation of low to moderate doses of caffeine. In experiment 1, there
      was no evidence that the range or magnitude of caffeine withdrawal symptoms
      differed when 300 mg of caffeine was consumed as a single dose in the morning
      versus 100 mg at three time points across the day. In experiment 2, both the
      range and severity of withdrawal increased as a function of caffeine maintenance
      dose (100, 300, and 600 mg/day), with even the lowest dose (100 mg) producing
      significant caffeine withdrawal. Experiment 3 showed that when individuals were
      maintained on 300 mg caffeine/day and tested with a range of lower doses (200,
      100, 50, 25, and 0 mg/day), a substantial reduction in caffeine consumption
      (</=100 mg/day) was necessary for the manifestation of caffeine withdrawal.
      Experiment 4 manipulated duration of exposure to caffeine (1, 3, 7, or 14 days of
      300 mg/day) and showed that caffeine withdrawal occurred after as little as 3
      days of caffeine exposure, with a somewhat increased severity of withdrawal
      observed after 7 or 14 days of exposure. As a whole, this set of experiments
      provides the most complete parametric characterization of caffeine withdrawal to
      date and suggests that caffeine physical dependence can occur under more modest
      conditions (i.e., fewer doses per day, lower daily dose, shorter duration of
      exposure) than previously recognized.

PMID- 10087017
TI  - Interaction between neutral endopeptidase and angiotensin converting enzyme
      inhibition in rats with myocardial infarction: effects on cardiac hypertrophy and
      angiotensin and bradykinin peptide levels.
AB  - Combined inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin
      converting enzyme (ACE) is a candidate therapy for hypertension and cardiac
      failure. Given that NEP and ACE metabolize angiotensin (Ang) and bradykinin (BK)
      peptides, we investigated the effects of NEP inhibition and combined NEP and ACE
      inhibition on Ang and BK levels in rats with myocardial infarction. We
      administered the NEP inhibitor ecadotril (0, 0.1, 1, 10, and 100 mg/kg/day),
      either alone or together with the ACE inhibitor perindopril (0.2 mg/kg/day) by 12
      hourly gavage from day 2 to 28 after infarction. Ecadotril increased urine cyclic
      GMP and BK-(1-9) excretion. Perindopril potentiated the effect of ecadotril on
      urine cyclic GMP excretion. Neither perindopril nor ecadotril reduced cardiac
      hypertrophy when administered separately, whereas the combination of perindopril
      and 10 or 100 mg/kg/day ecadotril reduced heart weight/body weight ratio by 10%.
      Administration of ecadotril to perindopril-treated rats decreased plasma Ang-(1
      7) levels, increased cardiac BK-(1-9) levels, and increased Ang II levels in
      plasma, kidney, aorta, and lung. These data demonstrate interactions between the
      effects of NEP and ACE inhibition on remodeling of the infarcted heart and on Ang
      and BK peptide levels. Whereas increased cardiac BK-(1-9) levels may contribute
      to the reduction of cardiac hypertrophy, the reduction in plasma Ang-(1-7) levels
      and increase in Ang II levels in plasma and tissues may compromise the
      therapeutic effects of combined NEP/ACE inhibition.

PMID- 10087018
TI  - Nitrocinnamoyl and chlorocinnamoyl derivatives of dihydrocodeinone: in vivo and
      in vitro characterization of mu-selective agonist and antagonist activity.
AB  - Two 14beta-p-nitrocinnamoyl derivatives of dihydrocodeinone, 14beta-(p
      nitrocinnamoylamino)-7,8-dihydrocodeinone (CACO) and N-cyclopropylmethylnor
      14beta-(p-nitrocinnamoylamino)- 7, 8-dihydrocodeinone (N-CPM-CACO), and the
      corresponding chlorocinnamoylamino analogs, 14beta-(p-chlorocinnamoylamino)-7, 8
      dihydrocodeinone (CAM) and N-cyclopropylmethylnor-14beta-(p-chlorocinnamoylamino)
      -7, 8-dihydrocodeinone (MC-CAM), were tested in opioid receptor binding assays
      and the mouse tail-flick test to characterize the opioid affinity, selectivity,
      and antinociceptive properties of these compounds. In competition binding assays,
      all four compounds bound to the mu opioid receptor with high affinity. When
      bovine striatal membranes were incubated with any of the four dihydrocodeinones,
      binding to the mu receptor was inhibited in a concentration-dependent, wash
      resistant manner. Saturation binding experiments demonstrated that the wash
      resistant inhibition of mu binding was due to a decrease in the Bmax value for
      the binding of the mu-selective peptide [3H][D-Ala2, MePhe4,Gly(ol)5] enkephalin
      and not a change in the Kd value, suggesting an irreversible interaction of the
      compounds with the mu receptor. In the mouse 55 degrees C warm water tail-flick
      test, both CACO and N-CPM-CACO acted as short-term mu-selective agonists when
      administered by i. c.v. injection, whereas CAM and MC-CAM produced no measurable
      antinociception at doses up to 30 nmol. Pretreatment of mice for 24 h with any of
      the four dihydrocodeinone derivatives produced a dose-dependent antagonism of
      antinociception mediated by the mu but not the delta or kappa receptors. Long
      term antagonism of morphine-induced antinociception lasted for at least 48 h
      after i.c. v. administration. Finally, shifts in the morphine dose-response lines
      after 24-h pretreatment with the four dihydrocodeinone compounds suggest that the
      nitrocinnamoylamino derivatives may produce a greater magnitude long-term
      antagonism of morphine-induced antinociception than the chlorocinnamoylamino
      analogs.

PMID- 10087019
TI  - kappa- and mu-Opioid inhibition of N-type calcium currents is attenuated by 4beta
      phorbol 12-myristate 13-acetate and protein kinase C in rat dorsal root ganglion
      neurons.
AB  - In rat dorsal root ganglion neurons, activation of kappa- and mu-opioid receptors
      decreases N-type calcium current, whereas a constitutively active form of protein
      kinase C (PKC; i.e., PKM, a PKC catalytic subunit fragment) increases N-type
      calcium current. PKC also attenuates inhibition of calcium current by several G
      protein-linked neurotransmitter systems. We examined the effects of activation of
      endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) and dialysis of
      cells with PKM and a pseudosubstrate inhibitor PKC(19-31) (PKC-I) on kappa- and
      mu-opioid-mediated inhibition of calcium current, calcium current amplitude, and
      rundown. PMA modestly increased peak calcium current and substantially reduced
      calcium current "rundown," effects blocked by PKC-I. In contrast, PKC-I decreased
      calcium current and increased current rundown. PMA attenuated morphine-,
      dynorphin A-, and U50, 488- but not pentobarbitol-related inhibition of calcium
      current. Similar effects were seen with intracellular dialysis of PKM.
      Intracellular PKC-I did not block opioid inhibition of calcium current but did
      reverse PMA and PKM effects on opioid receptor coupling to calcium channels.
      Because neither PMA nor PKM changed the proportion of omega-CgTX-inhibited
      current, their effects were not due to a decrease in the proportion of N-type
      current. After omega-CgTX treatment, there were no differences in the dynorphin A
      effects on control and PMA- or PKM-treated neurons, suggesting that PKC primarily
      affected coupling to N-type calcium channels. These data suggest that in acutely
      dissociated rat dorsal root ganglion neurons, endogenous PKC is required for
      maintenance of calcium current, may play a role in regulation of neuronal calcium
      channels, and could be involved in tolerance and/or cross-talk inhibition of
      opioid responsiveness.

PMID- 10087020
TI  - A-Current down-modulated by sigma receptor in frog pituitary melanotrope cells
      through a G protein-dependent pathway.
AB  - Gramicidin perforated patch-clamp recordings were used to study the effects of
      two sigma 1 receptor ligands, (+)-N-cyclopropylmethyl-N-methyl-1, 4-diphenyl-1
      ethyl-but-3-en-1-ylamine hydrochloride (JO 1784) and (+)-pentazocine, on the
      transient outward potassium current (IA) in cultured frog melanotrope cells. (+)
      Pentazocine reversibly decreased the current amplitude in a dose-dependent
      manner. The effects of (+)-pentazocine were mimicked by JO 1784 and were markedly
      reduced by the sigma 1 receptor antagonist, N, N-dipropyl-2-[4-methoxy-3-2(2
      phenylethoxy)phenyl]-ethylamine monohydrochloride (NE 100). Inactivation rate of
      IA was best fitted with a double exponential function, yielding time constants of
      23.7 and 112.5 ms. (+)-Pentazocine (20 microM) accelerated the current decay,
      decreasing the time constants to 10.7 and 59 ms, respectively. Current-voltage
      experiments revealed that (+)-pentazocine (20 microM) did neither modify the open
      state I/V curves nor the voltage dependence of IA. However, (+)-pentazocine (20
      microM) shifted the steady-state inactivation curve toward more negative
      potentials and increased the time constant of the time-dependent removal of
      inactivation. In whole-cell experiments, internal dialysis of guanosine-5'-O-(3
      thiophosphate) (100 microM) irreversibly prolonged the response to (+)
      pentazocine. In addition, cholera toxin pretreatment (1 microgram. ml-1; 12 h)
      suppressed the inhibition of IA by (+)-pentazocine (20 microM). It is concluded
      that in frog melanotrope cells, a cholera toxin-sensitive, G protein-dependent
      inhibition of IA through a sigma 1 receptor activation, at least partially,
      underlies the excitatory effect of sigma ligands.

PMID- 10087021
TI  - Comparative pharmacokinetics of vinblastine after a 96-hour continuous infusion
      in wild-type mice and mice lacking mdr1a P-glycoprotein.
AB  - To determine the tissue-specific impact of P-glycoprotein on the accumulation of
      a substrate drug, we have studied the tissue distribution of vinblastine in
      mdr1a(-/-) and wild-type mice at approximately similar, relatively low plasma
      levels. Vinblastine was administered as a 96-h continuous infusion at dose rates
      of 1 to 10 microgram/h, which were delivered by a s.c.-implanted osmotic pump.
      Drug concentrations were determined in plasma and tissues by HPLC. In comparison
      to wild-type mice, 4.4- to 9.6-fold higher drug concentrations were observed in
      the brains of mdr1a(-/-) mice (p </=. 014), whereas a 2-fold increase was found
      in the heart (p =.014) and the intestinal tissues (p </=.028). No or only slight
      differences were observed in all other tissues. These results indicate that,
      except for the brain and, to a lesser extent, the heart and the intestinal
      tissues, P-glycoprotein does not protect individual organs against vinblastine.
      Given its polarized cell-specific and organ-specific distribution and its
      affinity for a broad range of compounds, it is suggested that P-glycoprotein has
      mainly evolved to provide a general protection of the complete organism against
      potentially toxic substrates by inhibiting their uptake and by mediating their
      transport from the internal to the external environment. For the clinical
      application of reversal agents, these data indicate that, in general, a blockade
      of endogenous P-glycoprotein will probably not result in an increased
      accumulation of the coadministered anticancer drug in complete organs, but,
      possibly, only in classes of cells making up a fraction of an organ.

PMID- 10087022
TI  - Modeling geriatric depression in animals: biochemical and behavioral effects of
      olfactory bulbectomy in young versus aged rats.
AB  - Geriatric depression exhibits biological and therapeutic differences relative to
      early-onset depression. We studied olfactory bulbectomy (OBX), a paradigm that
      shares major features of human depression, in young versus aged rats to determine
      mechanisms underlying these differences. Young OBX rats showed locomotor
      hyperactivity and a loss of passive avoidance and tactile startle. In contrast,
      aged OBX animals maintained avoidance and startle responses but showed greater
      locomotor stimulation; the aged group also exhibited decreased grooming and
      suppressed feeding with novel presentation of chocolate milk, effects which were
      not seen in young OBX. These behavioral contrasts were accompanied by greater
      atrophy of the frontal/parietal cortex and midbrain in aged OBX. Serotonin
      transporter sites were increased in the cortex and hippocampus of young OBX rats,
      but were decreased in the aged OBX group. Cell signaling cascades also showed age
      dependent effects, with increased adenylyl cyclase responses to monoaminergic
      stimulation in young OBX but no change or a decrease in aged OBX. These data
      indicate that there are biological distinctions in effects of OBX in young and
      aged animals, which, if present in geriatric depression, provide a mechanistic
      basis for differences in biological markers and drug responses. OBX may provide a
      useful animal model with which to test therapeutic interventions for geriatric
      depression.

PMID- 10087023
TI  - Cimetidine transport in brush-border membrane vesicles from rat small intestine.
AB  - In previous studies, sulfoxide metabolite was observed in animal and human
      intestinal perfusions of cimetidine and other H2-antagonists. A sequence of
      follow-up studies is ongoing to assess the intestinal contributions of drug
      metabolism and drug and metabolite transport to variable drug absorption. An
      evaluation of these contributions to absorption variability is carried out in
      isolated fractions of the absorptive cells to uncouple the processes involved. In
      this report, data is presented on the drug entry step from a study on
      [3H]cimetidine uptake into isolated brush-border membrane vesicles from rat small
      intestine. A saturable component for cimetidine uptake was characterized with a
      Vmax and Km (mean +/- S.E.M.) of 6.1 +/- 1.5 nmol/30s/mg protein and 8.4 +/- 2.0
      mM, respectively. Initial binding, and possibly intravesicular uptake, was
      inhibited by other cationic compounds including ranitidine, procainamide,
      imipramine, erythromycin, and cysteamine but not by TEA or by the organic anion,
      probenecid. Initial uptake was not inhibited by amino acids methionine, cysteine,
      or histidine, by the metabolite cimetidine sulfoxide, or by inhibitors of
      cimetidine sulfoxidation, methimazole, and diisothiocyanostilbene-2,2'-disulfonic
      acid. Equilibrium uptake was inhibited by ranitidine, procainamide, and
      cysteamine but not by erythromycin or imipramine. Initial cimetidine uptake was
      stimulated by an outwardly directed H+ gradient, and efflux was enhanced by an
      inwardly directed H+ gradient. Collapse of the H+ gradient as well as voltage
      clamping potential difference to zero significantly reduced initial cimetidine
      uptake. The data is supportive of both a cimetidine/H+ exchange mechanism and a
      driving-force contribution from an inside negative proton or cation diffusion
      potential.

PMID- 10087024
TI  - Precontraction with elevated concentrations of extracellular potassium enables
      both 5-HT1B and 5-HT2A "silent" receptors in rabbit ear artery.
AB  - The present study was conducted to determine the effect of a small (<10%) K+
      induced precontraction on the response to vasoconstrictors in the rabbit aorta
      and ear artery rings. In both tissues, 15 mM K+ shifted the methoxamine
      concentration response curve (CRC) approximately 2.4-fold to the left. There was
      no change in the sensitivity of the control and amplified CRCs to the alpha1
      adrenoceptor antagonist prazosin (100 nM). In the aorta, the CRC for serotonin
      was shifted 4.5-fold to the left in the presence of 15 mM K+, and both the
      control and amplified CRCs were antagonized equally by the 5-HT2A antagonist
      ketanserin (10 nM). In contrast, 16 and 20 mM K+ caused up to an approximately 60
      fold leftward shift of the serotonin CRC in the rabbit ear artery. This effect of
      16 mM K+ was not altered by mechanical removal of the endothelium or by in vitro
      denervation using 6-hydroxydopamine. The K+-amplified CRC was insensitive to 100
      nM prazosin at serotonin concentrations below 3 microM, but was significantly
      antagonized by 10 nM ketanserin, suggesting that 5-HT2A receptors are involved in
      the K+-amplified response. The 5-HT1B-selective antagonist, GR 127935, did not
      affect control responses to serotonin, but significantly blocked the K+-amplified
      response. Furthermore, the combination of ketanserin and GR 127935 produced a
      significantly greater blockade of the amplified response than either antagonist
      alone, supporting the conclusion that both 5-HT2A and 5-HT1B receptors mediate
      the K+-amplified response to serotonin in the rabbit ear artery.

PMID- 10087025
TI  - Formate-induced inhibition of photoreceptor function in methanol intoxication.
AB  - Formic acid is the toxic metabolite responsible for the retinal and optic nerve
      toxicity produced in methanol intoxication. Previous studies in our laboratory
      have documented formate-induced retinal dysfunction and histopathology in a
      rodent model of methanol intoxication. The present studies define the time and
      concentration dependence of formate-induced retinal toxicity in methanol
      intoxicated rats. Retinal function was assessed 24, 48, and 72 h after the
      initial dose of methanol by flicker electroretinographic measurements. Retinal
      histopathology was assessed at the same time intervals. Rod- and cone-mediated
      electroretinogram (ERG) responses were attenuated in a formate concentration- and
      time-dependent manner, and both retinal sensitivity and maximal responsiveness to
      light were diminished. Attenuation of UV-cone-mediated responses was temporally
      delayed in comparison to the functional deficits observed in the 15 Hz/510 nm
      responses, which have a rod-mediated component and occurred at significantly
      higher formate concentrations. Both 15 Hz/510 nm and UV-cone-mediated ERG
      responses were undetectable by 72 h; however, if light intensity was increased, a
      retinal ERG response could be recorded, indicating that photoreceptor function
      was profoundly attenuated, but not abolished, under these intoxication
      conditions. Functional changes preceded structural alterations. Histopathological
      changes were most pronounced in the outer retina with evidence of inner segment
      swelling, photoreceptor mitochondrial disruption, and the appearance of
      fragmented photoreceptor nuclei in the outer nuclear layer. The nature of both
      the functional and structural alterations observed are consistent with formate
      induced inhibition of mitochondrial energy production, resulting in photoreceptor
      dysfunction and pathology.

PMID- 10087026
TI  - Down-regulation models and modeling of testosterone production induced by
      recombinant human choriogonadotropin.
AB  - Chorionic gonadotropin (CG) is a glycoprotein hormone, whose action is mediated
      by the luteinizing hormone/CG receptor. Testosterone concentrations from six
      pituitary-desensitized, healthy male volunteers were obtained after four
      different administrations of recombinant-human CG (rhCG). We present a modeling
      study to provide a possible explanation for the observations that increased
      exposure to rhCG induces higher and then lower testosterone concentrations and
      that marked rebound effects are observed at the end of repeated administration of
      rhCG. We used semimechanistic models (in which flexible functions represent
      unknown parts of the models) to identify the relationship of rhCG concentrations
      to the testosterone levels. Based on the results obtained with the
      semimechanistic models, different mechanistic down-regulation models were devised
      and tested. The final model uses a one-compartment model to describe the
      endogenous production rate of testosterone; rhCG affects the production rate with
      a mechanism consistent with a two-site binding site, with effect proportional to
      one-site bound concentration. The modeling results indicate that when rhCG
      concentration increases, the testosterone production rate increases to 45 times
      the baseline value. However, at an rhCG concentration of more than about 30
      IU/liter, the production rate decreases. Simulations showed that both dose and
      dosing interval profoundly influence testosterone response to rhCG.

PMID- 10087027
TI  - Activation of peripheral kappa opioid receptors inhibits capsaicin-induced
      thermal nociception in rhesus monkeys.
AB  - 8-Methyl-N-vanillyl-6-nonenamide (capsaicin) was locally applied in the tail of
      rhesus monkeys to evoke a nociceptive response, thermal allodynia, which was
      manifested as reduced tail-withdrawal latencies in normally innocuous 46 degrees
      C water. Coadministration of three kappa opioid ligands, U50,488 (3.2-100
      microgram), bremazocine (0.1-3.2 microgram), and dynorphin A(1-13) (3.2-100
      microgram), with capsaicin in the tail dose-dependently inhibited capsaicin
      induced allodynia. This local antinociception was antagonized by a small dose of
      an opioid antagonist, quadazocine; (0.32 mg), applied in the tail; however, this
      dose of quadazocine injected s.c. in the back did not antagonize local U50,488.
      Comparing the relative potency of either agonist or antagonist after local and
      systemic administration confirmed that the site of action of locally applied
      kappa opioid agonists is in the tail. In addition, local nor-binaltorphimine
      (0.32 mg) and oxilorphan (0.1-10 microgram) antagonist studies raised the
      possibility of kappa opioid receptor subtypes in the periphery, which indicated
      that U50,488 produced local antinociception by acting on kappa1 receptors, but
      bremazocine acted probably on non-kappa1 receptors. These results provide
      functional evidence that activation of peripheral kappa opioid receptors can
      diminish capsaicin-induced allodynia in primates. This experimental pain model is
      a useful tool for evaluating peripherally antinociceptive actions of kappa
      agonists without central side effects and suggests new approaches for opioid pain
      management.

PMID- 10087028
TI  - Fatty acid block of the transient outward current in adult human atrium.
AB  - Fatty acids represent an essential source of fuel for the heart and play an
      important role in the mechanical, electrical, and synthetic activities of cardiac
      cells. Under pathological conditions, such as ischemia followed by reperfusion,
      the myocardium is exposed to very high levels of fatty acids, in particular the
      monounsaturated fatty acid, oleic acid. Elevated plasma fatty acids have been
      linked to an increased risk for cardiac arrhythmias. In other species, fatty
      acids have been shown to modulate several cardiac ion channels, most notably
      potassium channels. Virtually nothing is known about the actions of oleic acid on
      potassium channels in human heart. We therefore characterized the effects of
      oleic acid on the transient outward current, sustained current, and inwardly
      rectifying current, some of the major potassium channels present in human atrium,
      using the whole-cell patch clamp method. Exposure of cells to oleic acid (5
      microM) reduced the transient outward potassium current to 3.7 +/- 0.8 pA/pF (n =
      4) compared with 7.0 +/- 0.7 pA/pF (n = 4) (P <. 05) for cells not exposed. In
      contrast, oleic acid had little effect on either the sustained current (4.3 +/-
      0.3 pA/pF, n = 4 for oleic acid versus 4.8 +/- 0.5, n = 5 for control) present
      after the decay of the transient outward current or on the amplitude of IK1
      measured at -100 mV (1.4 +/- 0.4 pA/pF, n = 4 for oleic acid versus 1.3 +/- 0. 4
      pA/pF, n = 6 for control). In addition, oleic acid significantly slowed the rate
      of recovery of the transient outward current, which is predicted to result in a
      use-dependent reduction in current amplitude in the beating heart. These results
      suggest a possible contributing role for oleic acid block of the transient
      outward current in the pathological consequences of myocardial ischemia.

PMID- 10087029
TI  - Synergistic interactions between ampakines and antipsychotic drugs.
AB  - Tests were made for interactions between antipsychotic drugs and compounds that
      enhance synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid-type glutamate receptors ("ampakines"). Typical and atypical
      antipsychotic drugs decreased methamphetamine-induced hyperactivity in rats; the
      effects of near or even subthreshold doses of the antipsychotics were greatly
      enhanced by the ampakines. Interactions between the ampakine CX516 and low doses
      of different antipsychotics were generally additive and often synergistic. The
      ampakine did not exacerbate neuroleptic-induced catalepsy, indicating that the
      interaction between the different pharmacological classes was selective. These
      results suggest that positive modulators of cortical glutamatergic systems may be
      useful adjuncts in treating schizophrenia.

PMID- 10087030
TI  - Nitric oxide is the predominant mediator for neurogenic vasodilation in porcine
      pial veins.
AB  - The innervation pattern and the vasomotor response of the potential transmitters
      in the porcine pial veins were investigated morphologically and
      pharmacologically. The porcine pial veins were more densely innervated by
      vasoactive intestinal polypeptide (VIP)- and neuropeptide Y-immunoreactive (I)
      fibers than were calcitonin gene-related peptide (CGRP)-I, choline
      acetyltransferase-I, Substance P (SP)-I, and NADPH diaphorase fibers. Serotonin
      (5-HT)-I fibers, which were not detected in normal control pial veins, were
      observed in isolated pial veins after incubation with 5-HT (1 microM). 5-HT-I
      fibers, however, were not observed when incubation with 5-HT was performed in the
      presence of guanethidine (1 microM), suggesting that 5-HT was taken up into the
      sympathetic nerves. In vitro tissue bath studies demonstrated that porcine pial
      veins in the presence of active muscle tone relaxed on applications of exogenous
      5-HT, CGRP, SP, VIP, and sodium nitroprusside, whereas exogenous norepinephrine
      and neuropeptide Y induced only constrictions. Transmural nerve stimulation (TNS)
      did not elicit any response in pial veins in the absence of active muscle tone.
      However, in the presence of active muscle tone, pial veins relaxed exclusively on
      TNS. This tetrodotoxin-sensitive relaxation was not affected by receptor
      antagonists for VIP, CGRP, 5-HT, or SP but was blocked by L-glutamine (1 mM) and
      abolished by Nomega-nitro-L-arginine (10 microM) and Nomega-nitro-L-arginine
      methyl ester (10 microM). The inhibition by L-glutamine, Nomega-nitro-L-arginine,
      and Nomega-nitro-L-arginine methyl ester was reversed by L-arginine and L
      citrulline but not by their D-enantiomers. These results demonstrate that the
      vasomotor effect of all potential transmitters except 5-HT in the pial veins
      examined resembles that in cerebral arteries. Although porcine pial veins receive
      vasodilator and constrictor nerves, a lack of constriction on TNS suggests that
      the dilator nerves that release nitric oxide may play a predominant role in
      regulating porcine pial venous tone.

PMID- 10087031
TI  - Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids:
      effect of ethanol training dose and dosing procedure.
AB  - A number of endogenous steroids exhibit rapid, nongenomic effects on the central
      nervous system and are called neuroactive steroids. The rapid mechanisms of
      action include modulation of gamma-aminobutyric acid type A (GABAA) and N-methyl
      D-aspartate (NMDA) receptors, which are two receptors implicated in the
      behavioral effects of ethanol. It was hypothesized that neuroactive steroids that
      positively modulate GABAA receptors or negatively modulate NMDA receptors,
      analogous to the actions of ethanol, would produce discriminative stimulus
      effects similar to ethanol. Two groups of male Long-Evans rats (n = 6-8/group)
      were trained to discriminate between 1.0 or 2.0 g/kg ethanol (i.g.) and water
      (i.g.). The neuroactive steroids allopregnanolone, pregnanolone, epipregnanolone,
      allotetrahydrodeoxycorticosterone, pregnanolone sulfate, epipregnanolone sulfate,
      dehydroepiandrosterone, dehydroepiandrosterone sulfate, pregnenolone, and
      pregnenolone sulfate (PS), all administered i.p., were tested for substitution
      with acute and cumulative dosing procedures (n = 4-8/steroid). The GABAA-positive
      modulatory steroids allopregnanolone, pregnanolone, and
      allotetrahydrodeoxycorticosterone substituted for ethanol, as did the low
      efficacy steroid 3beta,5beta-P. GABAA-negative modulators, such as
      dehydroepiandrosterone sulfate and PS, and all of the NMDA modulators tested,
      including PS, pregnanolone sulfate, and epipregnanolone sulfate, did not
      substitute for ethanol. These results show that certain endogenously occurring
      neuroactive steroids produce discriminative stimulus effects similar to those of
      ethanol.

PMID- 10087032
TI  - The regulation of dopamine transmission by metabotropic glutamate receptors.
AB  - Receptor subtype nonselective metabotropic glutamate receptor (mGluR) agonists
      have been shown to regulate the release of dopamine. The eight mGluR subtypes
      have been pharmacologically categorized into three groups, and the present study
      used in vivo microdialysis to examine the capacity of mGluR subgroup-selective
      drugs to modulate the extracellular levels of dopamine in the nucleus accumbens.
      By administering the drugs in the dialysis buffer, it was found that the group 3
      mGluR agonist L-amino-4-phosphonobutyrate produced a dose-dependent reduction in
      extracellular dopamine, whereas the group 1 agonist 3,5-dihydroxyphenylglycine
      was ineffective. The group 2 agonist (2S,1'R,2'R,3'R)-2-(2, 3
      dicarboxycyclopropyl)glycine produced a reduction that was biphasic with respect
      to dose. The group 2/3 antagonist alpha-methyl-4-phosphnophenylglycine elicited a
      dose-dependent increase in extracellular dopamine that was antagonized by
      coperfusion with either the L-type calcium channel blocker diltiazem or the group
      3 agonist L-amino-4-phosphonobutyrate. These data demonstrate that group 3 and to
      a lesser extent group 2 mGluR may presynaptically regulate dopamine release or
      reuptake. Moreover, there exists significant in vivo glutamatergic tone on group
      2/3 mGluRs to suppress extracellular dopamine levels.

PMID- 10087033
TI  - Antinociceptive properties of the new alkaloid, cis-8, 10-di-N-propyllobelidiol
      hydrochloride dihydrate isolated from Siphocampylus verticillatus: evidence for
      the mechanism of action.
AB  - The antinociceptive action of the alkaloid cis-8, 10-di-n-propyllobelidiol
      hydrochloride dehydrate (DPHD), isolated from Siphocampylus verticillatus, given
      i.p., p.o., i.t., or i.c.v., was assessed in chemical and thermal models of
      nociception in mice, such as acetic acid-induced abdominal constriction, formalin
      and capsaicin-induced licking, and hot-plate and tail-flick tests. DPHD given by
      i.p., p.o., i.t., or i.c.v. elicited significant and dose-related
      antinociception. At the ID50 level, DPHD was about 2- to 39-fold more potent than
      aspirin and dipyrone, but it was about 14- to 119-fold less potent than morphine.
      Its analgesic action was reversed by treatment of animals with p
      chlorophenylalanine, naloxone, cyprodime, naltrindole, nor-binaltrorphimine, L
      arginine, or pertussis toxin. Its action was also modulated by adrenal-gland
      hormones but was not affected by gamma-aminobutyric acid type A or type B
      antagonist, bicuculine, or phaclofen, nor was it affected by glibenclamide. DPHD,
      given daily for up to 7 days, did not develop tolerance to itself nor did it
      induce cross-tolerance to morphine. However, animals rendered tolerant to
      morphine presented cross-tolerance to DPHD. The antinociception of DPHD was not
      secondary to its anti-inflammatory effect, nor was it associated with nonspecific
      effects such as muscle relaxation or sedation. DPHD, in contrast to morphine, did
      not decrease charcoal meal transit in mice, nor did it inhibit electrical field
      stimulation of the guinea pig ileum or mouse vas deferens in vitro. Thus, DPHD
      produces dose-dependent and pronounced systemic, spinal, and supraspinal
      antinociception in mice, including against the neurogenic nociception induced by
      formalin and capsaicin. Its antinociceptive effect involves multiple mechanisms
      of action, namely interaction with mu, delta, or kappa opioid systems, L-arginine
      nitric oxide and serotonin pathways, activation of Gi protein sensitive to
      pertussis toxin, and modulation by endogenous glucocorticoids.

PMID- 10087034
TI  - S-16924, a novel, potential antipsychotic with marked serotonin1A agonist
      properties. IV. A drug discrimination comparison with clozapine.
AB  - The novel benzodioxopyrrolidine (S-16924) displays a clozapine-like profile of
      interaction with multiple monoaminergic receptors, in addition to potent agonist
      activity at serotonin (5-HT)1A receptors. S-16924 (2.5 mg/kg i.p.) and clozapine
      (5.0 mg/kg i.p.) generated robust discriminative stimuli (DS) and displayed full
      mutual generalization. The D4 antagonists L-745,870 and S-18126, the D1/D5
      antagonist SCH-39166, and the D3 antagonist S-14297 showed at most partial
      generalization to S-16924 and clozapine. The D2/D3 antagonist raclopride fully
      generalized to S-16924, but only partially generalized to clozapine. The 5-HT2A
      antagonist MDL-100, 907 fully generalized to S-16924 and two further 5-HT2A
      antagonists, fananserin and SR-46349, showed partial generalization. However, MDL
      100,907, fananserin, and SR-46349 showed less pronounced generalization to
      clozapine. Similarly, the 5-HT2C antagonists SB-200,646 and SB-206,553 more
      markedly generalized to S-16924 than to clozapine. The 5-HT1A receptor agonist
      (+/-)-8-dihydroxy-2-(di-n-propylamino) tetralin generalized fully to S-16924 but
      not to clozapine. Full generalization was obtained to both S-16924 and clozapine
      for the clozapine congeners, olanzapine and quetiapine. In distinction, the
      benzisoxazole, risperidone, and the phenylindole, sertindole, weakly generalized
      to S-16924 and clozapine. However, the benzisoxazole ziprasidone, which possesses
      5-HT1A agonist properties, generalized fully to S-16924 but not to clozapine.
      Finally, the muscarinic antagonist scopolamine generalized fully to clozapine and
      partially to S-16924. In conclusion, S-16924 and clozapine display both
      communalities and differences in their "compound" DS; this likely reflects their
      respective complex patterns of interaction with multiple monoaminergic receptors.
      Although no specific receptor was identified as underlying the clozapine DS, 5
      HT1A agonist as well as D2 and 5-HT2A/2C antagonist properties contribute to the
      S-16924 DS.

PMID- 10087035
TI  - A new CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of
      (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride in humans.
AB  - (+)-Cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) is a
      newly developed drug as a platelet-activating factor receptor antagonist. The
      disposition of SM-12502 was investigated in plasma from 28 healthy Japanese
      volunteers after a single i.v. administration of SM-12502. Three of 28 subjects
      were phenotyped as poor metabolizers (PMs). Genomic DNAs from three extensive
      metabolizers or three PMs of SM-12502 were analyzed by Southern blot analysis
      with CYP2A6 cDNA as a probe. DNAs from three PMs digested with SacI and SphI
      showed novel restriction fragment length polymorphisms (RFLPs); one type without
      4.5- and 2.6-kb fragments and a weak density of a 6.4-kb fragment (E-type), and
      the other type without 7.1- and 5.5-kb restriction fragments (C'-type) as
      compared with three extensive metabolizers, respectively. The deletional
      restriction fragments specific to three PMs in SacI- and SphI-RFLPs were
      identified as CYP2A6. Using polymerase chain reaction-RFLP analyses of the gene
      from the three PMs, we found that the exon 1, exon 8, and exon 9 in CYP2A6 were
      absent. A new RFLP characterized by SacI and SphI was found to be due to the
      entire gene deletion of the three exons and was associated with the decreased
      metabolism of SM-12502. This study demonstrates a new deletional allele in the
      human CYP2A6 gene responsible for the poor metabolic phenotype of SM-12502.

PMID- 10087036
TI  - Chronic lithium treatment inhibits amiloride-sensitive sodium transport in the
      rat distal nephron.
AB  - Chronic treatment of rats with lithium leads to Na+ loss and a reduced
      antinatriuretic response to aldosterone, suggesting that lithium reduces
      conductive Na+ transport in the distal nephron. This was investigated in the
      present study by measuring the renal response to aldosterone infusion followed by
      amiloride in chronically instrumented conscious rats given lithium for 3 to 4
      weeks to achieve plasma Li+ concentrations of approximately 0.5 mM. A servo
      controlled infusion system was used to maintain sodium and water homeostasis,
      thereby preventing misinterpretation of the findings as a consequence of drug
      induced changes in Na+ balance. In a control group of rats, Na+ excretion
      decreased in response to aldosterone (p <.01) and subsequent amiloride
      administration led to a marked increase in Na+ excretion (p <.001). In contrast,
      in the lithium-treated group, there was no significant response to either
      aldosterone or amiloride. It is concluded that long-term treatment with lithium,
      even when plasma Li+ concentrations are below 1 mM, reduces aldosterone
      stimulated Na+ transport through the amiloride-sensitive Na+ channels in the
      principal cells of the distal nephron.

PMID- 10087037
TI  - Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal
      peptide transporter (hPEPT1) expressed in a mammalian cell line.
AB  - The results of previous work performed in our laboratory using an in situ
      perfusion technique in rats and rabbit apical brush border membrane vesicles have
      suggested that the intestinal uptake of valacyclovir (VACV) appears to be
      mediated by multiple membrane transporters. Using these techniques, it is
      difficult to characterize the transport kinetics of VACV with each individual
      transporter in the presence of multiple known or unknown transporters. The
      purpose of this study was to characterize the interaction of VACV and the human
      intestinal peptide transporter using Chinese hamster ovary (CHO) cells that
      overexpress the human intestinal peptide transporter (hPEPT1) gene. VACV uptake
      was significantly greater in CHO cells transfected with hPEPT1 than in cells
      transfected with only the vector, pcDNA3. The optimum pH for VACV uptake was
      determined to occur at pH 7.5. Proton cotransport was not observed in hPEPT1/CHO
      cells, consistent with previously observed results in tissues and Caco-2 cells.
      VACV uptake was concentration dependent and saturable with a Michaelis-Menten
      constant and maximum velocity of 1.64 +/- 0.06 mM and 23.34 +/- 0.36 nmol/mg
      protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO
      cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1
      dominates the intestinal transport properties of VACV in vitro. VACV uptake was
      markedly inhibited by various dipeptides and beta-lactam antibiotics, and Ki
      values of 12.8 +/- 2.7 and 9.1 +/- 1.2 mM were obtained for Gly-Sar and
      cefadroxil at pH 7.5, respectively. The present results demonstrate that VACV is
      a substrate for the human intestinal peptide transporter in hPEPT1/CHO cells and
      that although transport is pH dependent, proton cotransport is not apparent.
      Also, the results demonstrate that the hPEPT1/CHO cell system has use in
      investigating the transport kinetics of drugs with the human intestinal peptide
      transporter hPEPT1; however, the extrapolation of these transport properties to
      the in vivo situation requires further investigation.

PMID- 10087038
TI  - Differences in pharmacological properties of dopamine release between the
      substantia nigra and striatum: an in vivo electrochemical study.
AB  - The properties of dopamine (DA) release in the rat substantia nigra (SN) and
      striatum were investigated using high-speed chronoamperometric recordings in
      brain slices. In both brain regions, a 2-min bath superfusion with 30 mM KCl
      produced robust DA-like electrochemical signals, with the mean amplitude of the
      signal being >10-fold greater in the striatum than the SN. The reproducibility of
      the response was confirmed by a second stimulus (S2)/first-stimulus (S1) ratio of
      >0.8 in both regions. The bath application of tetrodotoxin significantly reduced
      the S2/S1 ratio in both the striatum and SN, implicating the requirement for
      voltage-sensitive sodium channels in the DA-release process. However, the
      application of cadmium chloride, a nonselective blocker of voltage-sensitive
      calcium channels, reduced the S2/S1 ratio only in the striatum and not within the
      SN. Moreover, removal of Ca2+ from the buffer did not significantly affect
      release within the SN, despite a >85% reduction in release within the striatum.
      In addition, although the D2 receptor antagonist sulpiride enhanced the S2/S1
      ratio in the striatum, no effect of this agent was seen in the SN. Finally, the
      application of d-amphetamine produced DA-like electrochemical signals in both the
      striatum and SN. However, the amplitude of the d-amphetamine-evoked response,
      relative to the KCl-evoked release, was much smaller in the striatum than in the
      SN. Taken together, these data support the hypothesis that differences in the
      mechanism or mechanisms of release exist between somatodendritic and axonal
      elements within the nigrostriatal pathway.

PMID- 10087039
TI  - Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive
      contractile response in the guinea pig colon: evidence for M2/M3 receptor
      interactions.
AB  - The role of M2 and M3 receptors in the contractile and phosphoinositide responses
      elicited to oxotremorine-M was investigated in the guinea pig colon. Under
      standard conditions, both the contractile and phosphoinositide responses were
      insensitive to pertussis toxin and irreversibly antagonized by alkylation of M3
      receptors with N-(2-chloroethyl)-4-piperidinyl diphenylacetate. After treatment
      with N-(2-chloroethyl)-4-piperidinyl diphenylacetate, the remaining contractile
      response was sensitive to pertussis toxin and weakly antagonized by the M2- and
      M4-selective antagonist AF-DX 116. In contrast, the residual phosphoinositide
      response was unaffected by pertussis toxin. The pertussis toxin sensitivity of
      the remaining contractile response suggests that the M2 receptor is mediating the
      contraction, whereas its weak antagonism by AF-DX 116 suggests that an alternate
      muscarinic subtype mediates the response. To explain this enigma, we investigated
      a mathematical model for receptor action based on an interaction between two
      receptor subtypes (M2 and M3). This model predicts that a response mediated by
      both the M2 and M3 receptor can be pertussis toxin sensitive yet exhibit an
      antagonistic profile indicative of an M3 response.

PMID- 10087040
TI  - Mechanisms of delta-hexachlorocyclohexane toxicity: I. Relationship between
      altered ventricular myocyte contractility and ryanodine receptor function.
AB  - Several isomers of hexachlorocyclohexanes (HCHs) have been shown to be toxic to
      mammals. Previous studies have revealed that the delta isomer (delta-HCH) was
      particularly potent toward disrupting Ca2+ homeostasis in a variety of excitable
      and nonexcitable cells and altering contractility of cardiac muscle. The effects
      of the delta and gamma isomers of HCH were further investigated on isolated
      ventricular myocytes from guinea pig and on single cardiac ryanodine receptor
      (RyR2) Ca2+-release channels from cardiac SR vesicles. Intracellular Ca2+
      transients were examined in electrically stimulated cells using the fluorescent
      dye indo-1, and twitch contractions of myocytes were analyzed using a video-based
      edge motion detection system. Exposure of myocytes to delta- but not gamma-HCH
      depressed the peak of intracellular Ca2+ transients and prolonged recovery time.
      These effects were correlated with the ability of delta-HCH to inhibit the
      binding of [3H]ryanodine, a conformationally sensitive probe for RyR2 function,
      to SR preparations (IC50 = 2 and 18 microM for high- and low-affinity
      interactions, respectively). Measurements of single-channel gating kinetics under
      voltage-clamp provided direct evidence of a potent isoform-selective activation
      of RyR2 by delta-HCH. Results from these studies revealed that delta-HCH alters
      Ca2+ homeostasis and contractility in cardiac myocytes and that the mechanism can
      be ascribed, at least in part, to a direct interaction with the RyR2 channel
      complex.

PMID- 10087041
TI  - Mechanisms of delta-hexachlorocyclohexane toxicity: II. Evidence for Ca2+
      dependent K+-selective ionophore activity.
AB  - delta-Hexachlorocyclohexane (delta-HCH) interacts with cardiac ryanodine
      sensitive Ca2+ channels (RyR2), accounting in part for altered Ca2+ transients
      and contractility (reported in companion report). Analysis of channel gating
      kinetics in the presence of delta-HCH also revealed a nonfluctuating membrane
      current that remained even after RyR2 channels were blocked. We further
      elucidated the nature of a direct interaction between delta-HCH and biological
      membranes by measuring ionic currents across planar lipid bilayers made from
      defined lipids lacking cellular protein using voltage-clamp. Dimethyl sulfoxide,
      in the presence or absence of 50 microM gamma-HCH (lindane) or delta-HCH,
      produced negligible steady-state current with symmetric 100 mM CsCl in the range
      of +/-50 mV. However, the addition of 50 microM Ca2+ to the bilayer chamber in
      the presence of delta-HCH induced a profound increase in ionic permeability that
      was not seen in the presence of gamma-HCH or dimethyl sulfoxide control.
      Significantly, the permeability increase 1) was proportional with increasing Ca2+
      to approximately 600 microM and saturated between 1 and 2 mM Ca2+ regardless of
      holding potential, 2) occurred only when delta-HCH and Ca2+ were added to the
      same side of the membrane, and 3) was independent of the order of addition or of
      the side of the membrane to which delta-HCH and Ca2+ was added. The Ca2+
      dependent current produced by delta-HCH was highly selective for monovalent
      cations (K+ >> Cs+ > Na+), with negligible conductance for Ca2+ or Cl-. In
      symmetric 100 mM K+, the conductance induced with 50 microM concentration each of
      delta-HCH and Ca2+ was 4.25 pA/mV. The results show that delta-HCH increases the
      ionic permeability of phospholipid membranes by two distinct Ca2+-dependent
      mechanisms: one mediated through RyR and the other mediated by a unique ionophore
      activity.

PMID- 10087042
TI  - Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral
      selectivity.
AB  - The antihyperalgesic properties of the opiate antidiarrheal agent loperamide (ADL
      2-1294) were investigated in a variety of inflammatory pain models in rodents.
      Loperamide exhibited potent affinity and selectivity for the cloned micro (Ki = 3
      nM) compared with the delta (Ki = 48 nM) and kappa (Ki = 1156 nM) human opioid
      receptors. Loperamide potently stimulated [35S]guanosine-5'-O-(3
      thio)triphosphate binding (EC50 = 56 nM), and inhibited forskolin-stimulated cAMP
      accumulation (IC50 = 25 nM) in Chinese hamster ovary cells transfected with the
      human mu opioid receptor. The injection of 0.3 mg of loperamide into the intra
      articular space of the inflamed rat knee joint resulted in potent antinociception
      to knee compression that was antagonized by naloxone, whereas injection into the
      contralateral knee joint or via the i.m. route failed to inhibit compression
      induced changes in blood pressure. Loperamide potently inhibited late-phase
      formalin-induced flinching after intrapaw injection (A50 = 6 microgram) but was
      ineffective against early-phase flinching or after injection into the paw
      contralateral to the formalin-treated paw. Local injection of loperamide also
      produced antinociception against Freund's adjuvant- (ED50 = 21 microgram) or tape
      stripping- (ED50 = 71 microgram) induced hyperalgesia as demonstrated by
      increased paw pressure thresholds in the inflamed paw. In all animal models
      examined, the potency of loperamide after local administration was comparable to
      or better than that of morphine. Loperamide has potential therapeutic use as a
      peripherally selective opiate antihyperalgesic agent that lacks many of the side
      effects generally associated with administration of centrally acting opiates.

PMID- 10087043
TI  - Antithrombotic efficacy of thrombin inhibitor L-374,087: intravenous activity in
      a primate model of venous thrombus extension and oral activity in a canine model
      of primary venous and coronary artery thrombosis.
AB  - The small molecule direct thrombin inhibitor L-374,087 was characterized across
      species in an in vitro activated partial thromboplastin clotting time (aPTT)
      assay and in vivo in rhesus monkey and dog thrombosis models. In vitro in rhesus,
      dog, and human plasma, L-374,087 concentrations eliciting 2-fold increases in
      aPTT were 0.25, 1.9, and 0.28 microM, respectively. In anesthetized rhesus
      monkeys, 300 microgram/kg bolus plus 12 microgram/kg/min and 300 microgram/kg
      bolus plus 30 microgram/kg/min L-374,087 i.v. infusions significantly reduced
      jugular vein thrombus extension, with both regimens limiting venous thrombus
      extension to 2-fold that of baseline thrombus mass compared with a 5-fold
      extension observed in the vehicle control group. Antithrombotic efficacy in the
      rhesus with the lower-dose regimen was achieved with 2.3- to 2.4-fold increases
      in aPTT and prothrombin time. In a conscious instrumented dog model of
      electrolytic vessel injury, the oral administration of two 10 mg/kg L-374,087
      doses 12 h apart significantly reduced jugular vein thrombus mass, reduced the
      incidence of and delayed time to occlusive coronary artery thrombosis, and
      significantly reduced coronary artery thrombus mass and ensuing posterolateral
      myocardial infarct size. Antithrombotic efficacy in the dog was achieved with 1.6
      to 2.0-fold increases in aPTT at 1 to 6 h after oral dosing with L-374,087.
      These results indicate significant antithrombotic efficacy against both venous
      and coronary arterial thrombosis with L-374,087 with only moderate elevations in
      aPTT or prothrombin time. The oral efficacy of L-374,087 characterizes this
      compound as a prototype for the further development of orally active direct
      thrombin inhibitors.

PMID- 10087044
TI  - Metabolism of the antimalarial endoperoxide Ro 42-1611 (arteflene) in the rat:
      evidence for endoperoxide bioactivation.
AB  - Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial
      activity of endoperoxides is attributed to iron(II)-mediated generation of carbon
      centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4'
      bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction
      with iron(II), was identified previously as the stable product of a reaction
      that, by inference, also yields a cyclohexyl radical. The activation of arteflene
      in vivo has been characterized with particular reference to enone formation.
      [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated
      male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered
      in bile over 5 h. In the majority of rats, the principal biliary metabolites were
      8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans
      isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/-
      1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h.
      The principal urinary metabolite appeared to be a glycine conjugate of a
      derivative of the enone. Biliary excretion of the glucuronide, but not of the
      enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively
      by rat and human liver microsomes but no enone was found. Bioactivation is a
      major pathway of arteflene's metabolism in the rat. Although the mechanism of in
      vivo bioactivation is unclear, the reaction is not catalyzed by microsomal
      cytochrome P-450 enzymes.

PMID- 10087045
TI  - Effects of (+)-HA-966, CGS-19755, phencyclidine, and dizocilpine on repeated
      acquisition of response chains in pigeons: systemic manipulation of central
      glycine sites.
AB  - The effects of i.m. injections of (+)-HA-966, a glycine-site antagonist at the N
      methyl-D-aspartate (NMDA) subtype of the glutamate receptor, its enantiomer (-)
      HA-966, the competitive glutamate antagonist CGS-19755, the uncompetitive
      glutamate antagonists phencyclidine and dizocilpine, and the micro opioid agonist
      morphine were evaluated in a repeated acquisition task in pigeons. All of the
      drugs produced dose-dependent decreases in rates of responding. The NMDA receptor
      and channel blockers and (+)-HA-966 appeared to have a greater effect on
      acquisition than did morphine at doses that did not fully suppress responding.
      The rate suppression and learning impairment produced by a large dose of (+)-HA
      966 (100 mg/kg) were completely prevented by coadministration of the glycine-site
      agonist D-serine (560 mg/kg) but not by its enantiomer, L-serine (1000 mg/kg). D
      Serine, however, produced incomplete antagonism of the effects of dizocilpine and
      phencyclidine and failed to alter those of CGS-19755. These findings provide
      evidence that reducing the activity of the NMDA subtype of the glutamate receptor
      through pharmacological action at any of three sites produces similar decrements
      in acquisition, and those produced through antagonism of the glycine site are
      differentially sensitive to the glycine-site agonist D-serine.

PMID- 10087046
TI  - Oxidized low-density lipoprotein as a delivery system for photosensitizers:
      implications for photodynamic therapy of atherosclerosis.
AB  - Photodynamic therapy is a promising new strategy in the treatment of
      cardiovascular diseases. Photodynamic therapy for vascular diseases may be
      improved by the specific delivery of photosensitizers to the atherosclerotic
      lesion. In this study, we studied whether oxidatively modified low-density
      lipoprotein (OxLDL) could be used as a specific carrier for photosensitizers,
      thereby using the scavenger receptor expressed on macrophages as a target. The
      photosensitizer aluminum phthalocyanine chloride (AlPc) was incorporated into
      OxLDL, and its photodynamic effects were studied. Macrophages (RAW 264.7) were
      incubated with various concentrations of OxLDL-AlPc for different periods. After
      illumination of the cells with red light, cytotoxicity was observed that was
      dependent on the time of illumination and incubation. Macrophages incubated with
      OxLDL-AlPc that were not illuminated revealed no cytotoxicity. The uptake of the
      OxLDL-AlPc complexes was mediated by scavenger receptors expressed on
      macrophages. In the presence of the polyanion polyinosinic acid, a specific
      ligand for scavenger receptors, no cytotoxicity could be observed. Serum
      incubations of the OxLDL-AlPc complexes revealed that these complexes stay intact
      after incubation. No redistribution of AlPc to other plasma (lipo-) proteins
      could be detected, and 80-90% of the AlPc remained associated with the OxLDL
      particle. These results indicate that OxLDL may function as a specific delivery
      system for photosensitizers to the scavenger receptors expressed on the
      macrophages in the atherosclerotic lesion, increasing the beneficial effects of
      photodynamic therapy for cardiovascular diseases.

PMID- 10087047
TI  - Cyclosporin exerts a direct fibrogenic effect on human tubulointerstitial cells:
      roles of insulin-like growth factor I, transforming growth factor beta1, and
      platelet-derived growth factor.
AB  - To assess the direct fibrogenic effects of cyclosporin A (CyA) on the human
      tubulointerstitium, primary cultures of human renal proximal tubule cells (PTC)
      and renal cortical fibroblasts (CF) were incubated for 24 h with various
      concentrations of CyA. Cytotoxicity was confirmed in both cell populations by
      dose-dependent inhibition of thymidine incorporation, viability, and PTC apical
      sodium-hydrogen exchange activity (ethylisopropylamiloride-sensitive apical 22Na+
      uptake). Compared with controls, both 500 and 1000 ng/ml CyA significantly
      stimulated CF collagen synthesis (proline incorporation 4.6 +/- 0.4, 6.5 +/- 0.8,
      and 7.1 +/- 1.0%, respectively; p <.05) and inhibited matrix metalloproteinase-2
      (100%, 85.7 +/- 10.0%, and 38.8 +/- 9.2%) and matrix metalloproteinase-9 activity
      (100%, 110.6 +/- 19.0%, and 49.9 +/- 12.8%). CyA did not affect CF secretion of
      transforming growth factor beta1, but markedly stimulated insulin-like growth
      factor-I (IGF-I) secretion and inhibited secretion of both IGF-I binding protein
      (IGFBP)-3 and IGFBP-2. CyA-induced CF collagen synthesis was abrogated by 5
      microgram/ml anti-IGF-I receptor antibody, but not by 5 microgram/ml murine
      nonimmune globulin. Increasing concentrations of CyA progressively augmented PTC
      secretion of the fibrogenic cytokines transforming growth factor-beta1 and
      platelet-derived growth factor. These results indicate that clinically relevant
      concentrations of CyA are directly toxic to PTC and CF, irrespective of
      hemodynamic effects, and promote interstitial fibrosis by inhibiting matrix
      degradation and stimulating cortical fibroblast collagen synthesis via induction
      of autocrine IGF-I action. The latter effect may be further accentuated by the
      ability of CyA to augment secretion of transforming growth factor beta1 and
      platelet-derived growth factor by PTCs.

PMID- 10087048
TI  - Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic
      acetylcholine receptor.
AB  - Neonatal mice resist the lethal effect of Waglerin-1. Because Waglerin-1 blocks
      the nicotinic acetylcholine receptor of mature end-plates, the appearance of
      lethality may result from the epsilon- for gamma-subunit substitution. In support
      of this hypothesis, adult knockout (KO) mice lacking the gene coding for the
      epsilon-subunit resist the lethal effect of Waglerin-1. In contrast, heterozygous
      litter mates respond to Waglerin-1 like adult wild-type mice. In vitro
      application of 1 microM Waglerin-1 inhibited spontaneous miniature end-plate
      potentials and evoked end-plate potentials of adult wild-type and heterozygous KO
      mice. Both miniature end-plate potentials and end-plate potentials of neonatal
      wild-type and adult homozygous KO mice resisted Waglerin-1. Waglerin-1 decreased
      the end-plate response of adult wild-type mice to iontophoretically applied
      acetylcholine (ACh) with an IC50 value of 50 nM; 1 microM Waglerin-1 decreased
      the ACh response to 4 +/- 1% of control for adult heterozygous KO mice. In
      contrast, 1 microM Waglerin-1 decreased the ACh response to 73 +/- 2% of control
      for wild-type mice less than 11 days old and had no effect on the ACh response of
      adult homozygous KO mice. Between 11 and 12 days after birth, the suppressant
      effect of Waglerin-1 on wild-type end-plate responses to ACh dramatically
      increased. Waglerin-1 reduced binding of alpha-bungarotoxin to end-plates of
      adult but not neonatal wild-type mice. These data demonstrate that Waglerin-1
      selectively blocks the mouse muscle nicotinic acetylcholine receptor containing
      the epsilon-subunit.

PMID- 10087049
TI  - Characterization of the ATP-sensitive potassium channels (KATP) expressed in
      guinea pig bladder smooth muscle cells.
AB  - ATP-sensitive K+ (KATP) channels play an important role in the regulation of
      smooth muscle membrane potential. To investigate the properties of KATP channels
      in guinea pig urinary bladder smooth muscle cells, fluorescence-based assays were
      carried out with the membrane potential-sensitive probe bis-(1,3
      dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)]. The prototypical channel
      openers, including pinacidil, (-)-cromakalim, and diazoxide, elicited
      concentration-dependent decreases in membrane potential that were attenuated by
      glyburide. Similar responses were evoked by a reduction in intracellular ATP
      levels by metabolic inhibition. The observed rank order potency (EC50) for
      evoking membrane potential changes by potassium channel openers, P1075 (53 nM)
      approximately Bay X 9228 > (-)-cromakalim approximately ZD6169 approximately
      pinacidil > Bay X 9227 approximately ZM244085 > diazoxide (59 microM), showed a
      good correlation with that of bladder smooth muscle relaxation, as assessed by
      isolated tissue bath studies. The maximal efficacies of (-)-cromakalim,
      pinacidil, Bay X 9228, and ZD6169 were comparable with the response achieved by
      the reference activator P1075. Whole cell currents in bladder smooth muscle cells
      were increased in both inward and outward directions by P1075 and were reversed
      by glyburide to control levels. The molecular composition assessed by reverse
      transcriptase-polymerase chain reaction analysis using subunit-specific primers
      revealed the presence of mRNA for inward rectifying potassium channel (KIR6.2)
      and sulfonylurea receptors (SUR)2B and SUR1. The subunit profile together with
      pharmacological properties suggests that the KATP channel in bladder smooth
      muscle cells could be composed of SUR2B associated with a single inward
      rectifier, KIR6.2. In summary, these studies have characterized the
      pharmacological profile using fluorescent imaging plate reader-based membrane
      potential techniques and provide evidence for the molecular identity of KATP
      channels expressed in guinea pig bladder smooth muscle cells.

PMID- 10087050
TI  - In vitro cell cycle arrest, in vivo action on solid metastasizing tumors, and
      host toxicity of the antimetastatic drug NAMI-A and cisplatin.
AB  - The effects of NAMI-A (imidazolium trans-imidazoledimethyl sulfoxide
      tetrachlororuthenate) are compared with cisplatin on tumor cells cultured in
      vitro at doses of 1 to 100 microM and on tumor metastases in vivo at maximum
      tolerated doses. Using mouse tumors that metastasize to the lungs, NAMI-A given
      i.p. for 6 consecutive days at 35 mg/kg/day, was effective independently of the
      tumor line being treated and of the stage of metastasis growth. Conversely,
      cisplatin (2 mg/kg/day for 6 days) was as effective as NAMI-A on MCa mammary
      carcinoma and TS/A adenocarcinoma and less effective than NAMI-A on Lewis lung
      carcinoma. Cisplatin reduced body weight gain and spleen weight during treatment
      and was much more toxic than NAMI-A on liver sinusoids, kidney tubules, and lung
      epithelium. In vitro NAMI-A caused a transient cell cycle arrest of tumor cells
      in the premitotic G2/M phase, whereas cisplatin caused a progressive dose
      dependent disruption of cell cycle phases. Correspondingly, NAMI-A did not modify
      cell growth, whereas cisplatin caused a dose-dependent reduction of cell
      proliferation, as determined by sulforhodamine B test. Thus, NAMI-A, unlike
      cisplatin, is a potent agent for the treatment of solid tumor metastases as well
      as when these tumor lesions are in an advanced stage of growth. NAMI-A is endowed
      with a mechanism of action unrelated to direct tumor cell cytotoxicity, and such
      mechanism of action is responsible for a reduced host toxicity.

PMID- 10087051
TI  - Plasma levels of enalaprilat in chronic therapy of heart failure: relationship to
      adverse events.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are established as first-line
      therapy in chronic heart failure (CHF). However, little is known about the dosage
      plasma-level relationship of ACE inhibitors in CHF and its relation to drug
      induced adverse effects. We investigated 45 patients (age 55 +/- 10 years) with
      stable CHF who presented with a maintenance dosage of enalapril of either 5 mg
      b.i.d. (E10, n = 16), 10 mg b.i.d. (E20, n = 18), or 20 mg b.i.d. (E40, n = 11).
      This dosage was changed three times to treat all patients with lower, higher,
      and, finally, the initial dosage for 4 weeks each. Patients were examined
      clinically, by questionnaire, and by spiroergometry. In addition, neurohormones
      (atrial and brain natriuretic peptide and norepinephrine), enalaprilat trough
      levels, and serum potassium and creatinine were measured. Enalaprilat trough
      levels differed significantly between the three groups at study entry but also
      varied markedly within each group. In addition to the dose of enalapril, serum
      creatinine, severity of CHF, basal metabolic rate, and body weight significantly
      influenced enalaprilat trough levels (R2 =.84, p <.001). Within-patient
      comparisons revealed that serum creatinine (107 +/- 26 versus 102 +/- 20
      micromol/liter) and potassium (3.8 +/- 0.4 versus 3.7 +/- 0. 3mmol/liter) were
      higher, cough was more common (scored on a scale of 0-8: 1.7 +/- 2.1 versus 1.4
      +/- 1.8), and blood pressure was lower (systolic, 112 +/- 14 versus 117 +/- 13 mm
      Hg; diastolic, 66 +/- 9 versus 69 +/- 11 mm Hg) on the highest than on the lowest
      enalaprilat trough level (all p <.05). Highly variable enalaprilat trough levels
      and the fact that adverse effects were more common on high enalaprilat trough
      levels provide a rationale for individually adjusting ACE-inhibitor dose in case
      of adverse effects.

PMID- 10087052
TI  - Lovastatin-induced proliferation inhibition and apoptosis in C6 glial cells.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the rate-limiting
      enzyme in cholesterol biosynthesis. HMG-CoA reductase converts HMG-CoA to
      mevalonate, which is then converted into cholesterol or various isoprenoids
      through multiple enzymatic steps. In this study, we examined the cytotoxic
      effects of lovastatin, an HMG-CoA reductase inhibitor, in C6 glial cells.
      Lovastatin at concentrations higher than 10 microM suppressed cell proliferation
      and induced cell death, which were prevented completely by mevalonate (300
      microM). The data from lactate dehydrogenase assay and fluorescence microscopic
      assay using Hoechst 33342 and propidium iodide showed that mevalonate at a
      concentration of 100 microM could prevent lovastatin-induced cell death, whereas
      it could not prevent lovastatin-induced inhibition of cell proliferation. These
      data suggest that the lovastatin-induced interruption of cell cycle transition
      was not sufficient to induce cell death in C6 glial cells. In the presence of
      lovastatin at concentrations higher than 10 microM, DNA laddering, the typical
      finding of apoptosis, was identified. Lovastatin-induced apoptosis was prevented
      by mevalonate (100 microM). Both cycloheximide (0.5 microgram/ml) and actinomycin
      D (0.1 microgram/ml) prevented lovastatin-induced DNA laddering. In this study,
      we demonstrated that the cytotoxic effects of lovastatin fall into two
      categories: suppression of cell growth and induction of apoptosis in C6 glial
      cells.

PMID- 10087053
TI  - Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced
      hepatotoxicity.
AB  - The purpose of this study was to examine whether intracellular metallothionein
      (MT) protects against acetaminophen hepatotoxicity. MT-I/II knockout (MT-null)
      and control mice were given acetaminophen (150-500 mg/kg i.p.), and liver injury
      was assessed 24 h later. MT-null mice were more susceptible than controls to
      acetaminophen-induced lethality and hepatotoxicity, as evidenced by elevated
      serum enzyme activities and histopathology. Zinc pretreatment, a method of MT
      induction, protected against acetaminophen hepatotoxicity in control mice, but
      not in MT-null mice. The susceptibility of MT-null mice to acetaminophen
      hepatotoxicity was not due to the increased acetaminophen bioactivation, as
      cytochrome P-450 enzymes, and acetaminophen-reactive metabolites in bile and
      urine were not increased in MT-null mice. Western blots of liver cytosol
      indicated that acetaminophen covalent binding at 4 h increased with acetaminophen
      dose, but there was no consistent difference between control and MT-null mice.
      Acetaminophen injection depleted cellular glutathione similarly in both control
      and MT-null mice, but produced more lipid peroxidation in MT-null mice, as
      evidenced by the abundance of thiobarbiturate-reactive substances, and by
      immunohistochemical localization of 4-hydroxynonenal and malondialdehyde protein
      adducts. MT-null hepatocytes were more susceptible than control cells to
      oxidative stress and cytotoxicity produced by N-acetylbenzoquinoneimine, a
      reactive metabolite of acetaminophen, as determined by oxidation of 2', 7'
      dichlorofluorescin diacetate and lactate dehydrogenase leakage. In summary, this
      study demonstrated that MT deficiency renders animals more vulnerable to
      acetaminophen-induced hepatotoxicity. The increased sensitivity does not appear
      to be due to increased acetaminophen activation, glutathione depletion, or
      covalent binding, but appears to be associated with the antioxidant role of MT.

PMID- 10087054
TI  - Developmental regulation of expression of the D3 dopamine receptor in rat nucleus
      accumbens and islands of Calleja.
AB  - The dopamine D3 receptor (D3R) belongs to the D2 subfamily and is expressed in
      the rat brain in targets of the mesolimbic dopaminergic system. Little is known
      about its normal development and control by dopaminergic innervation. We studied
      developmental expression of D3R in the rat nucleus accumbens (NAC) and islands of
      Calleja (ISC). At postnatal day (P) 7, D3 binding sites and mRNA were low in both
      areas. By P14, D3R and mRNA concentrations were close to adult levels in the ISC,
      whereas, in the NAC, binding increased until 3 months after birth. Cellular
      concentrations of D3 mRNA in the ISC increased with age in conjunction with a
      decrease in the number of D3 positive cells. In the NAC, the number of positive
      cells increased, whereas cellular levels of expression remained unchanged.
      Neonatal 6-hydroxydopamine lesion caused age-dependent changes in D3R expression.
      D3 binding sites did not change at P7 or P14, but there was a reduction in the
      number of D3 mRNA positive neurons accompanied by an increase in cellular levels
      of D3 mRNA at P14, suggesting that changes occurred in a subset of neurons. Up
      regulation of D3 binding sites in NAC and ISC occurred 1 month after the lesion
      (P35) concomitant with a decrease in cellular levels of D3 mRNA and the number of
      D3 mRNA positive cells. At 3 months (P90) after the lesion, an increase in D3
      mRNA occurred with no change in D3 binding sites. D3R shows region-specific
      dynamics in receptor/mRNA expression during development and is sensitive to loss
      of dopamine in early postnatal development.

PMID- 10087055
TI  - Effect of phosducin on opioid receptor function.
AB  - Phosducin (Phd) regulates the function of G proteins by its ability to tightly
      bind Gbetagamma subunits. Because the internalization of opioid receptors as well
      as the activity of adenylyl cyclase (AC) activity depends on G proteins, we
      tested Phd on these parameters. NG 108-15 hybrid cells stably expressing the
      phosphoprotein were challenged with [D-penicillamine2,D-penicillamine5]enkephalin
      to inhibit cAMP generation, demonstrating an increased efficacy of the opioid on
      AC. Studying the binding of [35S]guanosine-5'-O-(gamma-thio)-triphosphate to
      membranes from Phd overexpressing cells, we found that [D-penicillamine2, D
      penicillamine5 ]enkephalin failed, in the presence of Phd (0.1 nM), to elevate
      incorporation of the nucleotide. Phd also strongly inhibited opioid-stimulated
      GTPase activity. NG 108-15 cells were also employed to investigate the effect of
      Phd on opioid receptor internalization. Control cells and cells overexpressing
      Phd were transiently transfected to express mu-opioid receptors fused to green
      fluorescence protein. In controls and in Phd overexpressing cells confocal
      microscopy identified fluorescence associated with the membrane. Time-lapse
      series microscopy of living control cells challenged with etorphine (1 microM)
      revealed receptor internalization within 30 min. In contrast, Phd overexpressing
      cells largely failed to respond to the opioid. Thus, in Phd overexpressing cells,
      opioids exhibit an increased efficacy despite the inhibitory action of the
      phosphoprotein on opioid-stimulated incorporation of [35S]guanosine-5'-O-(gamma
      thio)-triphosphate. We suggest that inhibition of GTPase stabilizes the opioid
      induced G protein Gi-GTP complex, which is believed to enhance AC inhibition.
      Finally, scavenging of Gbetagamma by Phd attenuates internalization of opioid
      receptors, which may contribute to the efficacy of opioids.

PMID- 10087056
TI  - Role of phosphatidylinositol 3-kinase in angiotensin II regulation of
      norepinephrine neuromodulation in brain neurons of the spontaneously hypertensive
      rat.
AB  - Chronic stimulation of norepinephrine (NE) neuromodulation by angiotensin II (Ang
      II) involves activation of the Ras-Raf-MAP kinase signal transduction pathway in
      Wistar Kyoto (WKY) rat brain neurons. This pathway is only partially responsible
      for this heightened action of Ang II in the spontaneously hypertensive rat (SHR)
      brain neurons. In this study, we demonstrate that the MAP kinase-independent
      signaling pathway in the SHR neuron involves activation of PI3-kinase and protein
      kinase B (PKB/Akt). Ang II stimulated PI3-kinase activity in both WKY and SHR
      brain neurons and was accompanied by its translocation from the cytoplasmic to
      the nuclear compartment. Although the magnitude of stimulation by Ang II was
      comparable, the stimulation was more persistent in the SHR neuron compared with
      the WKY rat neuron. Inhibition of PI3-kinase had no significant effect in the WKY
      rat neuron. However, it caused a 40-50% attenuation of the Ang II-induced
      increase in norepinephrine transporter (NET) and tyrosine hydroxylase (TH) mRNAs
      and [3H]-NE uptake in the SHR neuron. In contrast, inhibition of MAP kinase
      completely attenuated Ang II stimulation of NET and TH mRNA levels in the WKY rat
      neuron, whereas it caused only a 45% decrease in the SHR neuron. However, an
      additive attenuation was observed when both kinases of the SHR neurons were
      inhibited. Ang II also stimulated PKB/Akt activity in both WKY and SHR neurons.
      This stimulation was 30% higher and lasted longer in the SHR neuron compared with
      the WKY rat neuron. In conclusion, these observations demonstrate an exclusive
      involvement of PI3-kinase-PKB-dependent signaling pathway in a heightened NE
      neuromodulatory action of Ang II in the SHR neuron. Thus, this study offers an
      excellent potential for the development of new therapies for the treatment of
      centrally mediated hypertension.

PMID- 10087057
TI  - Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine
      transporter 2 knock-out mice.
AB  - Methamphetamine (METH) is a powerful psychostimulant that is increasingly abused
      worldwide. Although it is commonly accepted that the dopaminergic system and
      oxidation of dopamine (DA) play pivotal roles in the neurotoxicity produced by
      this phenylethylamine, the primary source of DA responsible for this effect has
      remained elusive. In this study, we used mice heterozygous for vesicular
      monoamine transporter 2 (VMAT2 +/- mice) to determine whether impaired vesicular
      function alters the effects of METH. METH-induced dopaminergic neurotoxicity was
      increased in striatum of VMAT2 +/- mice compared with wild-type mice as revealed
      by a more consistent DA and metabolite depletion and a greater decrease in
      dopamine transporter expression. Interestingly, increased METH neurotoxicity in
      VMAT2 +/- mice was accompanied by less pronounced increase in extracellular DA
      and indices of free radical formation compared with wild-type mice. These results
      indicate that disruption of vesicular monoamine transport potentiates METH
      induced neurotoxicity in vivo and point, albeit indirectly, to a greater
      contribution of intraneuronal DA redistribution rather than extraneuronal
      overflow on mediating this effect.

PMID- 10087058
TI  - Selective effects of neuronal-synaptobrevin mutations on transmitter release
      evoked by sustained versus transient Ca2+ increases and by cAMP.
AB  - Synaptobrevin is a key constituent of the synaptic vesicle membrane. The neuronal
      synaptobrevin (n-syb) gene in Drosophila is essential for nerve-evoked synaptic
      currents, but miniature excitatory synaptic currents (mESCs) remain even in the
      complete absence of this gene. To further characterize the defect in these
      mutants, we have examined conditions that stimulate secretion. Despite the
      inability of an action potential to trigger fusion, high K+ saline could increase
      the frequency of mESCs 4- to 17-fold in a Ca2+-dependent manner, and the rate of
      fusion approached 25% of that seen in wild-type synapses under the same
      conditions. Similarly, the mESC frequency in n-syb null mutants could be
      increased by a Ca2+ ionophore, A23187, and by black widow spider venom. Thus, the
      ability of the vesicles to fuse in response to sustained increases in cytosolic
      Ca2+ persisted in the absence of this protein. Tetanic stimulation could also
      increase the frequency of mESCs, particularly toward the end of a train and after
      the train of stimuli. In contrast, these mutants did not respond to an elevation
      of cAMP induced by an activator of adenylyl cyclase, forskolin, or a membrane
      permeable analog of cAMP, dibutyryl cAMP, which in wild-type synapses causes a
      marked increase in the mESC frequency even in the absence of external Ca2+. These
      results are discussed in the context of models that invoke a special role for n
      syb in coupling fusion to the transient, local changes in Ca2+ and an as yet
      unidentified target of cAMP.

PMID- 10087059
TI  - Rapid induction of functional and morphological continuity between severed ends
      of mammalian or earthworm myelinated axons.
AB  - The inability to rapidly restore the loss of function that results from severance
      (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a
      novel strategy to help alleviate this problem, we have developed in vitro
      procedures using Ca2+-free solutions of polyethylene glycol (PEG solutions),
      which within minutes induce functional and morphological continuity (PEG-induced
      fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in
      rats. Using a PEG-based hydrogel that binds to connective tissue to provide
      mechanical strength at the lesion site and is nontoxic to nerve tissues in
      earthworms and mammals, we have also developed in vivo procedures that
      permanently maintain earthworm myelinated medial giant axons whose functional and
      morphological integrity has been restored by PEG-induced fusion after axonal
      severance. In all these in vitro or in vivo procedures, the success of PEG
      induced fusion of sciatic or spinal axons and myelinated medial giant axons is
      measured by the restored conduction of action potentials through the lesion site,
      the presence of intact axonal profiles in electron micrographs taken at the
      lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the
      lesion site. These and other data suggest that the application of polymeric
      fusiogens (such as our PEG solutions), possibly combined with a tissue adherent
      (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and
      permanently repair cut or crushed axons in the PNS and CNS of adult mammals,
      including humans.

PMID- 10087060
TI  - The mitogen-activated protein kinase pathway mediates estrogen neuroprotection
      after glutamate toxicity in primary cortical neurons.
AB  - Pharmacological and biochemical approaches were used to elucidate the involvement
      of growth factor signaling pathways mediating estrogen neuroprotection in primary
      cortical neurons after glutamate excitotoxicity. We addressed the activation of
      mitogen-activated protein kinase (MAPK) signaling pathways, which are activated
      by growth factors such as nerve growth factor (NGF). Inhibition of MAPK signaling
      with the MAPK kinase inhibitor PD98059 blocks both NGF and estrogen
      neuroprotection in these neurons. These results correlate with a rapid and
      sustained increase in MAPK activity within 30 min of estrogen exposure. The
      involvement of signaling molecules upstream from MAPK was also examined to
      determine whether activation of MAPK by estrogen is mediated by tyrosine kinase
      activity. Estrogen produces a rapid, transient activation of src-family tyrosine
      kinases and tyrosine phosphorylation of p21(ras)-guanine nucleotide activating
      protein. Effects of estrogen on neuroprotection, as well as rapid activation of
      tyrosine kinase and MAPK activity, are blocked by the anti-estrogen ICI 182,780.
      This provides evidence that activation of the MAPK pathway by estrogen
      participates in mediating neuroprotection via an estrogen receptor. These results
      describe a novel mechanism by which cytoplasmic actions of the estrogen receptor
      may activate the MAPK pathway, thus broadening the understanding of effects of
      estrogen in neurons.

PMID- 10087061
TI  - A test of the cytosolic apolipoprotein E hypothesis fails to detect the escape of
      apolipoprotein E from the endocytic pathway into the cytosol and shows that
      direct expression of apolipoprotein E in the cytosol is cytotoxic.
AB  - Genetic evidence indicates that apolipoprotein E4 (apoE4) is a risk factor for
      the development of Alzheimer's disease. A controversial hypothesis proposes that
      apoE, a typical secretory protein, accesses the neuronal cytosol in which apoE3,
      but not apoE4, protects tau from hyperphosphorylation. However, no conclusive
      evidence for the presence of apoE in the cytosolic compartment has been
      presented. We designed a novel assay to test whether apoE can access the cytosol
      via escape from the endocytic pathway by incorporating a nuclear localization
      signal (NLS) into apoE. Control experiments demonstrated that apoE plus NLS
      (apoE+NLS) is chaperoned to the nucleus if it reaches the cytosolic compartment.
      When exogenous apoE+NLS was endocytosed by neuronal cells, no nuclear apoE was
      detected, indicating that apoE remains within the endocytic pathway and does not
      escape into the cytosol. Furthermore, we show that direct cytosolic expression of
      apoE is cytotoxic. These data argue that effects of apoE on the neuronal
      cytoskeleton and on neurite outgrowth are not mediated via cytosolic interactions
      but rather by actions originating at the cell surface.

PMID- 10087062
TI  - Chlorpromazine inhibits miniature GABAergic currents by reducing the binding and
      by increasing the unbinding rate of GABAA receptors.
AB  - Recent studies have emphasized that nonequilibrium conditions of postsynaptic
      GABAA receptor (GABAAR) activation is a key factor in shaping the time course of
      IPSCs (Puia et al., 1994; Jones and Westbrook, 1995). Such nonequilibrium,
      resulting from extremely fast agonist time course, may affect the interaction
      between pharmacological agents and postsynaptic GABAARs. In the present study we
      found that chlorpromazine (CPZ), a widely used antipsychotic drug known to
      interfere with several ligand and voltage-gated channels, reduces the amplitude
      and accelerates the decay of miniature IPSCs (mIPSCs). A good qualitative
      reproduction of the effects of CPZ on mIPSCs was obtained when mIPSCs were
      mimicked by responses to ultrafast GABA applications to excised patches. Our
      experimental data and model simulations indicate that CPZ affects mIPSCs by
      decreasing the binding (kon) and by increasing the unbinding (koff) rates of
      GABAARs. Because of reduction of kon by CPZ, the binding reaction becomes rate
      limiting, and agonist exposure of GABAARs during mIPSC is too short to activate
      the receptors to the same extent as in control conditions. The increase in
      unbinding rate is implicated as the mechanism underlying the acceleration of
      mIPSC decaying phase. The effect of CPZ on GABAAR binding rate, resulting in
      slower onset of GABA-evoked currents, provides a tool to estimate the speed of
      synaptic clearance of GABA. Moreover, the onset kinetics of recorded responses
      allowed the estimate the peak synaptic GABA concentration.

PMID- 10087063
TI  - A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term
      depression.
AB  - High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces
      long-term depression (LTD) of excitatory synaptic potentials recorded from
      striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a
      selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows
      that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited
      by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic
      stimulation and vice versa. Both forms of synaptic plasticity are blocked by
      intracellular 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), a selective
      inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP
      production in the spiny neuron is a key step. Accordingly, intracellular cGMP,
      activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS)
      inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7
      nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or
      zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S
      nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes
      further depression by HFS or zaprinast, and it is blocked by intracellular ODQ
      but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced
      by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the
      presence of NOS-positive terminals of striatal interneurons forming synaptic
      contacts with dendrites of spiny neurons. These findings represent the first
      demonstration that the NO/cGMP pathway exerts a feed-forward control on the
      corticostriatal synaptic plasticity.

PMID- 10087064
TI  - Adenylyl cyclase activation modulates activity-dependent changes in synaptic
      strength and Ca2+/calmodulin-dependent kinase II autophosphorylation.
AB  - Activation of the Ca2+- and calmodulin-dependent protein kinase II (CaMKII) and
      its conversion into a persistently activated form by autophosphorylation are
      thought to be crucial events underlying the induction of long-term potentiation
      (LTP) by increases in postsynaptic Ca2+. Because increases in Ca2+ can also
      activate protein phosphatases that oppose persistent CaMKII activation, LTP
      induction may also require activation of signaling pathways that suppress protein
      phosphatase activation. Because the adenylyl cyclase (AC)-protein kinase A
      signaling pathway may provide a mechanism for suppressing protein phosphatase
      activation, we investigated the effects of AC activators on activity-dependent
      changes in synaptic strength and on levels of autophosphorylated alphaCaMKII
      (Thr286). In the CA1 region of hippocampal slices, briefly elevating
      extracellular Ca2+ induced an activity-dependent, transient potentiation of
      synaptic transmission that could be converted into a persistent potentiation by
      the addition of phosphatase inhibitors or AC activators. To examine activity
      dependent changes in alphaCaMKII autophosphorylation, we replaced electrical
      presynaptic fiber stimulation with an increase in extracellular K+ to achieve a
      more global synaptic activation during perfusion of high Ca2+ solutions. In the
      presence of the AC activator forskolin or the protein phosphatase inhibitor
      calyculin A, this treatment induced a LTP-like synaptic potentiation and a
      persistent increase in autophosphorylated alphaCaMKII levels. In the absence of
      forskolin or calyculin A, it had no lasting effect on synaptic strength and
      induced a persistent decrease in autophosphorylated alphaCaMKII levels. Our
      results suggest that AC activation facilitates LTP induction by suppressing
      protein phosphatases and enabling a persistent increase in the levels of
      autophosphorylated CaMKII.

PMID- 10087065
TI  - Synaptic vesicle dynamics in rat fast and slow motor nerve terminals.
AB  - We have investigated whether rat motor nerve terminals with different in vivo
      activity patterns also have different vesicle trafficking characteristics. To do
      this, we monitored, using combined optical and electrical techniques, the rate of
      exocytosis (during different frequencies and patterns of activity), the
      releasable pool size, and the recycle time of synaptic vesicles in terminals on
      soleus (slow-twitch) and extensor digitorum longus [(EDL); fast-twitch] muscle
      fibers. EDL terminals had a higher initial quantal content (QC) than soleus, but
      during tonic or phasic stimulation at 20-80 Hz, EDL QC ran down to a greater
      extent than soleus QC. By recording loss of fluorescence from exocytosing
      vesicles labeled with the dye FM1-43, EDL terminals were found to destain faster
      than those in soleus. Simultaneous intracellular recording of end plate
      potentials, to count the number of vesicles released, permitted estimation of the
      total vesicle pool (VP) size and the recycle time by combining the optical and
      electrophysiological data. Soleus vesicle pool was larger than EDL, but recycle
      time was not significantly different. These terminals, therefore, are adapted to
      their in vivo activity patterns by alterations in QC and VP size but not recycle
      time.

PMID- 10087066
TI  - Nuclear and neuropil aggregates in Huntington's disease: relationship to
      neuropathology.
AB  - The data we report in this study concern the types, location, numbers, forms, and
      composition of microscopic huntingtin aggregates in brain tissues from humans
      with different grades of Huntington's disease (HD). We have developed a fusion
      protein antibody against the first 256 amino acids that preferentially recognizes
      aggregated huntingtin and labels many more aggregates in neuronal nuclei,
      perikarya, and processes in human brain than have been described previously.
      Using this antibody and human brain tissue ranging from presymptomatic to grade
      4, we have compared the numbers and locations of nuclear and neuropil aggregates
      with the known patterns of neuronal death in HD. We show that neuropil aggregates
      are much more common than nuclear aggregates and can be present in large numbers
      before the onset of clinical symptoms. There are also many more aggregates in
      cortex than in striatum, where they are actually uncommon. Although the striatum
      is the most affected region in HD, only 1-4% of striatal neurons in all grades of
      HD have nuclear aggregates. Neuropil aggregates, which we have identified by
      electron microscopy to occur in dendrites and dendritic spines, could play a role
      in the known dendritic pathology that occurs in HD. Aggregates increase in size
      in advanced grades, suggesting that they may persist in neurons that are more
      likely to survive. Ubiquitination is apparent in only a subset of aggregates,
      suggesting that ubiquitin-mediated proteolysis of aggregates may be late or
      variable.

PMID- 10087067
TI  - CNS wound healing is severely depressed in metallothionein I- and II-deficient
      mice.
AB  - To characterize the physiological role of metallothioneins I and II (MT-I+II) in
      the brain, we have examined the chronological effects of a freeze injury to the
      cortex in normal and MT-I+II null mice. In normal mice, microglia/macrophage
      activation and astrocytosis were observed in the areas surrounding the lesion
      site, peaking at approximately 1 and 3 d postlesion (dpl), respectively. At 20
      dpl, the parenchyma had regenerated. Both brain macrophages and astrocytes
      surrounding the lesion increased the MT-I+II immunoreactivity, peaking at
      approximately 3 dpl, and at 20 dpl it was similar to that of unlesioned mice. In
      situ hybridization analysis indicates that MT-I+II immunoreactivity reflects
      changes in the messenger levels. In MT-I+II null mice, microglia/macrophages
      infiltrated the lesion heavily, and at 20 dpl they were still present. Reactive
      astrocytosis was delayed and persisted at 20 dpl. In contrast to normal mice, at
      20 dpl no wound healing had occurred. The rate of apoptosis, as determined by
      using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling, was drastically increased in neurons of ipsilateral cortex of the MT
      I+II null mice. Our results demonstrate that MT-I+II are essential for a normal
      wound repair in the CNS, and that their deficiency impairs neuronal survival.

PMID- 10087068
TI  - Noninvasive measurements of the membrane potential and GABAergic action in
      hippocampal interneurons.
AB  - Neurotransmitters affect the membrane potential (Vm) of target cells by
      modulating the activity of receptor-linked ion channels. The direction and
      amplitude of the resulting transmembrane current depend on the resting level of
      Vm and the gradient across the membrane of permeant ion species. Vm, in addition,
      governs the activation state of voltage-gated channels. Knowledge of the exact
      level of Vm is therefore crucial to evaluate the nature of the neurotransmitter
      effect. However, the traditional methods to measure Vm, with microelectrodes or
      the whole-cell current-clamp technique, have the drawback that the recording
      pipette is in contact with the cytoplasm, and dialysis with the pipette solution
      alters the ionic composition of the interior of the cell. Here we describe a
      novel technique to determine the Vm of an intact cell from the reversal potential
      of K+ currents through a cell-attached patch. Applying the method to interneurons
      in hippocampal brain slices yielded more negative values for Vm than subsequent
      whole-cell current-clamp measurements from the same cell, presumably reflecting
      the development of a Donnan potential between cytoplasm and pipette solution in
      the whole-cell mode. Cell-attached Vm measurements were used to study GABAergic
      actions in intact CA1 interneurons. In 1- to 3-week-old rats, bath-applied GABA
      inhibited these cells by stabilizing Vm at a level depending on contributions
      from both GABAA and GABAB components. In contrast, in 1- to 4-d-old animals, only
      GABAA receptors were activated resulting in a depolarizing GABA response.

PMID- 10087069
TI  - Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid
      lipofuscinosis: evidence for partial response to insulin-like growth factor-1
      treatment.
AB  - The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative
      disorders with onset from infancy to adulthood that are manifested by blindness,
      seizures, and dementia. In NCL, lysosomes accumulate autofluorescent proteolipid
      in the brain and other tissues. The mnd/mnd mutant mouse was first characterized
      as exhibiting adult-onset upper and lower motor neuron degeneration, but closer
      examination revealed early, widespread pathology similar to that seen in NCL. We
      used the autofluorescent properties of accumulated storage material to map which
      CNS neuronal populations in the mnd/mnd mouse show NCL-like pathological changes.
      Pronounced, early accumulation of autofluorescent lipopigment was found in
      subpopulations of GABAergic neurons, including interneurons in the cortex and
      hippocampus. Staining for phenotypic markers normally present in these neurons
      revealed progressive loss of staining in the cortex and hippocampus of mnd/mnd
      mice, with pronounced hypertrophy of remaining detectable interneurons. In
      contrast, even in aged mutant mice, many hippocampal interneurons retained
      staining for glutamic acid decarboxylase. Treatment with insulin-like growth
      factor-1 partially restored interneuronal number and reduced hypertrophy in some
      subregions. These results provide the first evidence for the involvement of
      interneurons in a mouse model of NCL. Moreover, our findings suggest that at
      least some populations of these neurons persist in a growth factor-responsive
      state.

PMID- 10087070
TI  - Immunohistological studies of metabotropic glutamate receptor subtype 6-deficient
      mice show no abnormality of retinal cell organization and ganglion cell
      maturation.
AB  - Immature retinal ganglion cells (RGCs) initially show a multistratified dendritic
      pattern, and, during the postnatal period, these dendrites gradually monostratify
      into ON and OFF sublaminae. The selective agonist of group III metabotropic
      glutamate receptors (mGluR), L-2-amino-4-phosphonobutyrate (L-AP-4),
      hyperpolarizes ON bipolar cells and reduces glutamate release. On the basis of L
      AP-4-evoked inhibitory effects on ON-OFF segregation of developing RGCs, it has
      been hypothesized that glutamate-mediated synaptic activity is crucial for
      formation of the ON-OFF network. Gene-targeted ablation of mGluR6 specifically
      expressed in ON bipolar cells blocks normal ON responses but has been predicted
      to enhance glutamate release from ON bipolar cells. The mGluR6 knock-out mouse
      therefore provides a unique opportunity to investigate whether glutamate release
      and ON responses are important factors in the development of ON-OFF segregation.
      The combination of several different morphological analyses indicates that ON
      bipolar cells, as well as several distinct amacrine cells, in mGluR6 knock-out
      mice are normally distributed and correctly extend their terminals to defined
      retinal laminae. Importantly, both alpha and delta RGCs in adult mGluR6 knock-out
      mice are found monostratified into cell type-specific layers. Furthermore, no
      difference between wild-type and mGluR6 knock-out mice is observed in the
      maturation and dendritic stratification of developing RGCs. Hence, despite a
      deficit in normal ON responses, mGluR6 deficiency causes no abnormality in the
      retinal cellular organization nor in the stratifications of both ON bipolar cells
      and developing and mature RGCs. Based on these findings, we discuss several
      possible mechanisms that may underlie ON-OFF segregation of RGCs.

PMID- 10087071
TI  - Optical detection of synaptically induced glutamate transport in hippocampal
      slices.
AB  - Although it has long been believed that glial cells play a major role in
      transmitter uptake at synapses in the CNS, the relative contribution of glial and
      neuronal cells to reuptake of synaptically released glutamate has been unclear.
      Recent identification of the diverse glutamate transporter subtypes provides an
      opportunity to examine this issue. To monitor glutamate transporter activity, we
      optically detected synaptically induced changes of membrane potential from
      hippocampal CA1 field in slice preparations using a voltage-sensitive dye, RH155.
      In the presence of ionotropic glutamate-receptor blockers, synaptic inputs gave
      rise to a slow depolarizing response (SDR) in the dendritic field. The amplitude
      of SDR correlated well with presynaptic activities, suggesting that it was
      related to transmitter release. The SDR was found to be caused by the activities
      of glutamate transporters because it was not affected by blockers for GABAA,
      nACh, 5-HT3, P2X, or metabotropic glutamate receptors but was greatly reduced by
      dihydrokainate (DHK), a specific blocker for GLT-1 transporter, and by D, L-threo
      beta-hydroxyaspartate (THA), a blocker for EAAC, GLAST, and GLT-1 transporters.
      When SDR was detected with RH482 dye, which stains both glial and neuronal cells,
      1 mM DHK and 1 mM THA were equally effective in suppressing SDR. The SDR was very
      small in GLT-1 knockout mice but was maintained in gerbil hippocampi in which
      postsynaptic neurons were absent because of ischemia. Because GLT-1 transporters
      are exclusively expressed in astrocytes, our results provide direct evidence that
      astrocytes play the dominant role in sequestering synaptically released
      glutamate.

PMID- 10087072
TI  - Filopodial adhesion does not predict growth cone steering events in vivo.
AB  - Migration of growth cones is in part mediated by adhesive interactions between
      filopodia and the extracellular environment, transmitting forces and signals
      necessary for pathfinding. To elucidate the role of substrate adhesivity in
      growth cone pathfinding, we developed an in vivo assay for measuring filopodial
      substrate adhesivity using the well-characterized Ti pioneer neuron pathway of
      the embryonic grasshopper limb. Using time-lapse imaging and a combination of
      rhodamine-phalloidin injections and DiI labeling, we demonstrate that the
      filopodial retraction rate after treatment with cytochalasin D or elastase
      reflects the degree of filopodial-substrate adhesivity. Measurements of
      filopodial retraction rates along regions of known differing substrate
      adhesivities confirmed the use of this assay to examine filopodial-substrate
      adhesion during in vivo pathfinding events. We analyzed 359 filopodia from 22 Ti
      growth cones and found that there is no difference between the retraction rates
      of filopodia extending toward the correct target (on-axis) and filopodia
      extending away from the correct target (off-axis). These results indicate on-axis
      and off-axis filopodia have similar substrate adherence. Interestingly, we
      observed a 300% increase in the extension rates of on-axis filopodia during Ti
      growth cone turning events. Therefore, in addition to providing filopodia with
      important guidance information, regional cues are capable of modulating the
      filopodial extension rate. The homogeneity in filopodial retraction rates, even
      among these turning growth cones in which differential adhesivity might be
      expected to be greatest, strongly establishes that differential adhesion does not
      govern Ti pioneer neuron migration rate or pathfinding. We propose that the
      presence of local differences in receptor-mediated second messenger cascades and
      the resulting assembly of force-generating machinery may underlie the ability of
      filopodial contacts to regulate growth cone steering in vivo.

PMID- 10087073
TI  - Sonic hedgehog promotes neuronal differentiation of murine spinal cord precursors
      and collaborates with neurotrophin 3 to induce Islet-1.
AB  - Sonic hedgehog (Shh) is strongly implicated in the development of ventral
      structures in the nervous system. Addition of Sonic hedgehog protein to chick
      spinal cord explants induces floor plate and motoneuron development. Whether Shh
      acts directly to induce these cell types or whether their induction is mediated
      by additional factors is unknown. To further investigate the role of Shh in
      spinal neuron development, we have used low-density cultures of murine spinal
      cord precursor cells. Shh stimulated neuronal differentiation; however, it did
      not increase the proportion of neurons expressing the first postmitotic
      motoneuron marker Islet-1. Moreover, Shh did induce Islet-1 expression in neural
      tube explants, suggesting that it acts in combination with neural tube factors to
      induce motoneurons. Another factor implicated in motoneuron development is
      neurotrophin 3 (NT3), and when assayed in isolated precursor cultures, it had no
      effect on Islet-1 expression. However, the combination of N-terminal Shh and NT3
      induced Islet-1 expression in the majority of neurons in low-density cultures of
      caudal intermediate neural plate. Furthermore, in explant cultures, Shh-mediated
      Islet-1 expression was blocked by an anti-NT3 antibody. Previous studies have
      shown expression of NT3 in the region of motoneuron differentiation and that
      spinal fusimotor neurons are lost in NT3 knock-out animals. Taken together, these
      findings suggest that Shh can act directly on spinal cord precursors to promote
      neuronal differentiation, but induction of Islet-1 expression is regulated by
      factors additional to Shh, including NT3.

PMID- 10087074
TI  - Differential effects of apamin- and charybdotoxin-sensitive K+ conductances on
      spontaneous discharge patterns of developing retinal ganglion cells.
AB  - The spontaneous discharge patterns of developing retinal ganglion cells are
      thought to play a crucial role in the refinement of early retinofugal
      projections. To investigate the contributions of intrinsic membrane properties to
      the spontaneous activity of developing ganglion cells, we assessed the effects of
      blocking large and small calcium-activated potassium conductances on the temporal
      pattern of such discharges by means of patch-clamp recordings from the intact
      retina of developing ferrets. Application of apamin and charybdotoxin (CTX),
      which selectively block the small and large calcium-activated potassium channels,
      respectively, resulted in significant changes in spontaneous firings. In cells
      recorded from the oldest animals [postnatal day 30 (P30)-P45], which manifested
      relatively sustained discharge patterns, application of either blocker induced
      bursting activity. With CTX the bursts were highly periodic, short in duration,
      and of high frequency. In contrast, with apamin the interburst intervals were
      longer, less regular, and lower in overall spike frequency. These differences
      between the effects of the two blockers on spontaneous activity were documented
      by spectral analysis of discharge patterns. Filling cells from which recordings
      were made with Lucifer yellow revealed that these effects were obtained in all
      three morphological classes of cells: alpha, beta, and gamma. These findings
      provide the first evidence that apamin- and CTX-sensitive K+ conductances can
      have differential effects on the spontaneous discharge patterns of retinal
      ganglion cells. Remarkably, the bursts of activity obtained after apamin
      application in more mature neurons appeared very similar to the spontaneous
      bursting patterns observed in developing neurons. These findings suggest that the
      maturation of calcium-activated potassium channels, particularly the apamin
      sensitive conductance, may contribute to the changes in spontaneous firings
      exhibited by retinal ganglion cells during the course of normal development.

PMID- 10087075
TI  - Topographic organization of human visual areas in the absence of input from
      primary cortex.
AB  - Recently, there has been evidence for considerable plasticity in primary sensory
      areas of adult cortex. In this study, we asked to what extent topographical maps
      in human extrastriate areas reorganize after damage to a portion of primary
      visual (striate) cortex, V1. Functional magnetic resonance imaging signals were
      measured in a subject (G.Y.) with a large calcarine lesion that includes most of
      primary visual cortex but spares the foveal representation. When foveal
      stimulation was present, intact cortex in the lesioned occipital lobe exhibited
      conventional retinotopic organization. Several visual areas could be identified
      (V1, V2, V3, V3 accessory, and V4 ventral). However, when stimuli were restricted
      to the blind portion of the visual field, responses were found primarily in
      dorsal extrastriate areas. Furthermore, cortex that had formerly shown normal
      topography now represented only the visual field around the lower vertical
      meridian. Several possible sources for this reorganized activity are considered,
      including transcallosal connections, direct subcortical projections to
      extrastriate cortex, and residual inputs from V1 near the margin of the lesion. A
      scheme is described to explain how the reorganized signals could occur based on
      changes in the local neural connections.

PMID- 10087076
TI  - The sexually dimorphic expression of androgen receptors in the song nucleus
      hyperstriatalis ventrale pars caudale of the zebra finch develops independently
      of gonadal steroids.
AB  - The development of sex differences in brain structure and brain chemistry ("brain
      sex") of vertebrates is frequently thought to depend entirely on gonadal steroids
      such as androgens and estrogens, which act on the brain at the genomic level by
      binding to intracellular transcription factors, the androgen receptors (ARs) and
      estrogen receptors (ERs). These hormone actions are thought to shift the brain
      from a monomorphic to a dimorphic phenotype. One prominent such example is the
      nucleus hyperstriatalis ventrale pars caudale (HVc) of the zebra finch (Poephila
      guttata), a set of cells in the caudal forebrain involved in the control of
      singing. In contrast with previous studies using nonspecific cell staining
      techniques, the size and neuron number of the HVc measured by the distribution of
      AR mRNA is already sexually dimorphic on posthatching day (P)9. No ARs or ERs are
      expressed in the HVc before day 9. Slice cultures of the caudal forebrain of P5
      animals show that the sexually dimorphic expression of AR mRNA in HVc is
      independent of the direct action of steroids on this nucleus or any of its
      immediate presynaptic or postsynaptic partners. Therefore, gonadal steroids do
      not appear to be directly involved in the initial sex difference in the
      expression pattern of AR mRNA, size, and neuron number of the HVc. Furthermore,
      we demonstrate that the initial steroid-independent size and its subsequent
      steroid-independent growth by extension linearly with the extension of the
      forebrain explains 60-70% of the masculine development of the HVc. Thus, we
      suggest that epigenetic factors such as the gonadal steroids modify but cannot
      overwrite the sex difference in HVc volume determined autonomously in the brain.

PMID- 10087077
TI  - GABAergic neurons that contain neuropeptide Y selectively target cells with the
      neurokinin 1 receptor in laminae III and IV of the rat spinal cord.
AB  - Neuropeptide Y (NPY) is contained in a population of GABAergic interneurons in
      the spinal dorsal horn and, when administered intrathecally, can produce
      analgesia. We previously identified a strong monosynaptic link between substance
      P-containing primary afferents and cells in lamina III or IV with the neurokinin
      1 (NK1) receptor. Because some of these cells belong to the spinothalamic tract,
      they are likely to have an important role in pain mechanisms. In this study, we
      used confocal microscopy to examine the input to lamina III/IV NK1 receptor
      immunoreactive neurons from NPY-containing axons. All of the cells studied
      received a dense innervation from NPY-immunoreactive axons, and electron
      microscopy revealed that synapses were often present at points of contact. Most
      NPY-immunoreactive boutons were also GABAergic, which supports the suggestion
      that they are derived from local neurons. The association between NPY-containing
      axons and NK1 receptor-immunoreactive neurons was specific, because postsynaptic
      dorsal column neurons (which were located in laminae III-V but did not possess
      NK1 receptors) and lamina I neurons with the NK1 receptor received significantly
      fewer contacts from NPY-immunoreactive axons. In addition, the NK1 receptor
      immunoreactive lamina III/IV cells received few contacts from nitric oxide
      synthase-containing axons (which belong to a different population of GABAergic
      dorsal horn neurons). The NPY-containing axons appeared to be targeted to the NK1
      receptor-immunoreactive neurons themselves rather than to their associated
      substance P-immunoreactive inputs. The dense innervation of these cells by NPY
      containing axons suggests that they may possess receptors for NPY and that
      activation of these receptors may contribute to NPY-mediated analgesia.

PMID- 10087078
TI  - Cortical visuomotor integration during eye pursuit and eye-finger pursuit.
AB  - To elucidate cortical mechanisms of visuomotor integration, we recorded whole
      scalp neuromagnetic signals from six normal volunteers while they were viewing a
      black dot moving linearly at the speed of 4 degrees /sec within a virtual
      rectangle. The dot changed its direction randomly once every 0.3-2 sec. The
      subject either (1) fixated a cross in the center of the screen (eye fixation
      task), (2) followed the moving dot with the eyes (eye pursuit task), or (3)
      followed the dot with both the eyes and the right index finger (eye-finger
      pursuit task). Prominent magnetic signals, triggered by the changes of the
      direction of the dot, were seen in all conditions, but they were clearly enhanced
      by the tasks and were strongest during the eye-finger pursuit task and over the
      anterior inferior parietal lobule (aIPL). Source modeling indicated activation of
      aIPL [Brodmann's area (BA) 40], the posterosuperior parietal lobule (SPL; BA 7),
      the dorsolateral frontal cortex (DLF; BA 6), and the occipital cortex (BA 18/19).
      The activation first peaked in the occipital areas, then in the aIPL and DLF, and
      some 50 msec later in the SPL. Our results suggest that all these areas are
      involved in visuomotor transformation, with aIPL playing a crucial role in this
      process.

PMID- 10087079
TI  - Stimulus-dependent translocation of kappa opioid receptors to the plasma
      membrane.
AB  - We examined the cellular and subcellular distribution of the cloned kappa opioid
      receptor (KOR1) and its trafficking to the presynaptic plasma membrane in
      vasopressin magnocellular neurosecretory neurons. We used immunohistochemistry to
      show that KOR1 immunoreactivity (IR) colocalized with vasopressin-containing cell
      bodies, axons, and axon terminals within the posterior pituitary. Ultrastructural
      analysis revealed that a major fraction of KOR1-IR was associated with the
      membrane of peptide-containing large secretory vesicles. KOR1-IR was rarely
      associated with the plasma membrane in unstimulated nerve terminals within the
      posterior pituitary. A physiological stimulus (salt-loading) that elicits
      vasopressin release also caused KOR1-IR to translocate from these vesicles to the
      plasma membrane. After stimulation, there was a significant decrease in KOR1-IR
      associated with peptide-containing vesicles and a significant increase in KOR1-IR
      associated with the plasma membrane. This stimulus-dependent translocation of
      receptors to the presynaptic plasma membrane provides a novel mechanism for
      regulation of transmitter release.

PMID- 10087080
TI  - Functionally independent components of the late positive event-related potential
      during visual spatial attention.
AB  - Human event-related potentials (ERPs) were recorded from 10 subjects presented
      with visual target and nontarget stimuli at five screen locations and responding
      to targets presented at one of the locations. The late positive response
      complexes of 25-75 ERP average waveforms from the two task conditions were
      simultaneously analyzed with Independent Component Analysis, a new computational
      method for blindly separating linearly mixed signals. Three spatially fixed,
      temporally independent, behaviorally relevant, and physiologically plausible
      components were identified without reference to peaks in single-channel
      waveforms. A novel frontoparietal component (P3f) began at approximately 140 msec
      and peaked, in faster responders, at the onset of the motor command. The scalp
      distribution of P3f appeared consistent with brain regions activated during
      spatial orienting in functional imaging experiments. A longer-latency large
      component (P3b), positive over parietal cortex, was followed by a postmotor
      potential (Pmp) component that peaked 200 msec after the button press and
      reversed polarity near the central sulcus. A fourth component associated with a
      left frontocentral nontarget positivity (Pnt) was evoked primarily by target-like
      distractors presented in the attended location. When no distractors were
      presented, responses of five faster-responding subjects contained largest P3f and
      smallest Pmp components; when distractors were included, a Pmp component appeared
      only in responses of the five slower-responding subjects. Direct relationships
      between component amplitudes, latencies, and behavioral responses, plus
      similarities between component scalp distributions and regional activations
      reported in functional brain imaging experiments suggest that P3f, Pmp, and Pnt
      measure the time course and strength of functionally distinct brain processes.

PMID- 10087081
TI  - Optic flow selectivity in the anterior superior temporal polysensory area, STPa,
      of the behaving monkey.
AB  - Earlier studies of neurons in the anterior region of the superior temporal
      polysensory area (STPa) have demonstrated selectivity for visual motion using
      stimuli contaminated by nonmotion cues, including texture, luminance, and form.
      The present experiments investigated the motion selectivity of neurons in STPa in
      the absence of form cues using random dot optic flow displays. The responses of
      neurons were tested with translation, rotation, radial, and spiral optic flow
      displays designed to mimic the types of motion that occur during locomotion. Over
      half of the neurons tested responded significantly to at least one of these
      displays. On a cell by cell basis, 60% of the neurons tested responded
      selectively to rotation, radial, and spiral motion, whereas 20% responded
      selectively to translation motion. The majority of neurons responded maximally to
      single-component optic flow displays but was also significantly activated by the
      spiral displays that contained their preferred component. Moreover, there was a
      bias in the selectivity of the neurons for radial expansion motion. These results
      suggest that neurons within STPa are contributing to the analysis of optic flow.
      Furthermore, the preponderance of cells selective for radial expansion provides
      evidence that this area may be specifically involved in the processing of forward
      locomotion and/or looming stimuli. Finally, these results provide carefully
      controlled physiological evidence for an extension and specialization of the
      motion-processing pathway into the anterior temporal lobe.

PMID- 10087082
TI  - Choline and selective antagonists identify two subtypes of nicotinic
      acetylcholine receptors that modulate GABA release from CA1 interneurons in rat
      hippocampal slices.
AB  - Neuronal nicotinic receptors (nAChR) are known to control transmitter release in
      the CNS. Thus, this study was aimed at exploring the diversity and localization
      of nAChRs present in CA1 interneurons in rat hippocampal slices. The use of a U
      tube as the agonist delivery system was critical for the reliable detection of
      nicotinic responses induced by brief exposure of the neurons to ACh or to the
      alpha7 nAChR-selective agonist choline. The present study demonstrated that CA1
      interneurons, in addition to expressing functional alpha7 nAChRs, also express
      functional alpha4beta2-like nAChRs and that activation of both receptors
      facilitates an action potential-dependent release of GABA. Depending on the
      experimental condition, one of the following nicotinic responses was recorded
      from the interneurons by means of the patch-clamp technique: a nicotinic whole
      cell current, depolarization accompanied by action potentials, or GABA-mediated
      postsynaptic currents (PSCs). Responses mediated by alpha7 nAChRs were short
      lasting, whereas those mediated by alpha4beta2 nAChRs were long-lasting. Thus,
      phasic or tonic inhibition of CA1 interneurons may be achieved by selective
      activation of alpha7 or alpha4beta2 nAChRs, respectively. It can also be
      suggested that synaptic levels of choline generated by hydrolysis of ACh in vivo
      may be sufficient to control the activity of the alpha7 nAChRs. The finding that
      methyllycaconitine and dihydro-beta-erythroidine (antagonists of alpha7 and
      alpha4beta2 nAChRs, respectively) increased the frequency and amplitude of
      GABAergic PSCs suggests that there is an intrinsic cholinergic activity that
      sustains a basal level of nAChR activity in these interneurons.

PMID- 10087083
TI  - Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in
      transgenic mice carrying mutated presenilin-1 and amyloid precursor protein
      transgenes.
AB  - Cholinergic deficits are one of the most consistent neuropathological landmarks
      in Alzheimer's disease (AD). We have examined transgenic mouse models (PS1M146L,
      APPK670N,M671L) and a doubly transgenic line (APPK670N,M671L + PS1M146L) that
      overexpress mutated AD-related genes [presenilin-1 (PS1) and the amyloid
      precursor protein (APP)] to investigate the effect of AD-related gene
      overexpression and/or amyloidosis on cholinergic parameters. The size of the
      basal forebrain cholinergic neurons and the pattern of cholinergic synapses in
      the hippocampus and cerebral cortex were revealed by immunohistochemical staining
      for choline acetyltransferase and the vesicular acetylcholine transporter,
      respectively. At the time point studied (8 months), no apparent changes in either
      the size or density of cholinergic synapses were found in the PS1M146L mutant
      relative to the nontransgenic controls. However, the APPK670N,M671L mutant showed
      a significant elevation in the density of cholinergic synapses in the frontal and
      parietal cortices. Most importantly, the double mutant (APPK670N,M671L +
      PS1M146L), which had extensive amyloidosis, demonstrated a prominent diminution
      in the density of cholinergic synapses in the frontal cortex and a reduction in
      the size of these synapses in the frontal cortex and hippocampus. Nonetheless, no
      significant changes in the size of basal forebrain cholinergic neurons were
      observed in these three mutants. This study shows a novel role of APP and a
      synergistic effect of APP and PS1 that correlates with amyloid load on the
      reorganization of the cholinergic network in the cerebral cortex and hippocampus
      at the time point studied.

PMID- 10087084
TI  - Multifunctional laryngeal motoneurons: an intracellular study in the cat.
AB  - We studied the patterns of membrane potential changes in laryngeal motoneurons
      (LMs) during vocalization, coughing, swallowing, sneezing, and the aspiration
      reflex in decerebrate paralyzed cats. LMs, identified by antidromic activation
      from the recurrent laryngeal nerve, were expiratory (ELMs) or inspiratory (ILMs)
      cells that depolarized during their respective phases in eupnea. During
      vocalization, most ELMs depolarized and most ILMs hyperpolarized. Some ILMs
      depolarized slightly during vocalization. During coughing, ELMs depolarized
      abruptly at the transition from the inspiratory to the expiratory phase. In one
      third of ELMs, this depolarization persisted throughout the abdominal burst. In
      the remainder ("type A"), it was interrupted by a transient repolarization. ILMs
      exhibited a membrane potential trajectory opposite to that of type A ELMs during
      coughing. During swallowing, the membrane potential of ELMs decreased transiently
      at the onset of the hypoglossal burst and then depolarized strongly during the
      burst. ILMs hyperpolarized sharply at the onset of the burst and depolarized as
      hypoglossal activity ceased. During sneezing, ELMs and ILMs exhibited membrane
      potential changes similar to those of type A ELMs and ILMs during coughing.
      During the aspiration reflex, ELMs and ILMs exhibited bell-shaped
      hyperpolarization and depolarization trajectories, respectively. We conclude that
      central drives to LMs, consisting of complex combinations of excitation and
      inhibition, vary during vocalization and upper airway defensive reflexes. This
      study provides data for analysis of the neuronal networks that produce these
      various behaviors and analysis of network reorganization caused by changes in
      dynamic connections between the respiratory and nonrespiratory neuronal networks.

PMID- 10087085
TI  - Patterns of spontaneous purkinje cell complex spike activity in the awake rat.
AB  - The olivocerebellar system is known to generate periodic synchronous discharges
      that result in synchronous (to within 1 msec) climbing fiber activation of
      Purkinje cells (complex spikes) organized in parasagittally oriented strips.
      These results have been obtained primarily in anesthetized animals, and so the
      question remains whether the olivocerebellar system generates such patterns in
      the awake animal. To this end, multiple electrode recordings of crus 2a complex
      spike activity were obtained in awake rats conditioned to execute tongue
      movements in response to a tone. After removal of all movement- and tone-related
      activity, the remaining data were examined to characterize spontaneous complex
      spike activity in the alert animal. Spontaneous complex spikes occurred at an
      average firing rate of 1 Hz and a clear approximately 10 Hz rhythmicity. Analysis
      of the autocorrelograms using a rhythm index indicated that the large majority of
      Purkinje cells displayed rhythmicity, similar to that in the anesthetized
      preparation. In addition, the patterns of synchronous complex spike activity were
      also similar to those observed in the anesthetized preparation (i.e.,
      simultaneous activity was found predominantly among Purkinje cells located within
      the same parasagittally oriented strip of cortex). The results provide
      unequivocal evidence that the olivocerebellar system is capable of generating
      periodic patterns of synchronous activity in the awake animal. These findings
      support the extrapolation of previous results obtained in the anesthetized
      preparation to the waking state and are consistent with the timing hypothesis
      concerning the role of the olivocerebellar system in motor coordination.

PMID- 10087086
TI  - Role of primate superior colliculus in preparation and execution of anti-saccades
      and pro-saccades.
AB  - We investigated how the brain switches between the preparation of a movement
      where a stimulus is the target of the movement, and a movement where a stimulus
      serves as a landmark for an instructed movement elsewhere. Monkeys were trained
      on a pro-/anti-saccade paradigm in which they either had to generate a pro
      saccade toward a visual stimulus or an anti-saccade away from the stimulus to its
      mirror position, depending on the color of an initial fixation point. Neural
      activity was recorded in the superior colliculus (SC), a structure that is known
      to be involved in the generation of fast saccades, to determine whether it was
      also involved in the generation of anti-saccades. On anti-saccade trials,
      fixation during the instruction period was associated with an increased activity
      of collicular fixation-related neurons and a decreased activity of saccade
      related neurons. Stimulus-related and saccade-related activity was reduced on
      anti-saccade trials. Our results demonstrate that the anti-saccade task involves
      (and may require) the attenuation of preparatory and stimulus-related activity in
      the SC to avoid unwanted pro-saccades. Because the attenuated pre-saccade
      activity that we found in the SC may be insufficient by itself to elicit correct
      anti-saccades, additional movement signals from other brain areas are presumably
      required.

PMID- 10087087
TI  - Immediate-early gene expression in the inferior mesenteric ganglion and colonic
      myenteric plexus of the guinea pig.
AB  - Activation of neurons in the inferior mesenteric ganglion (IMG) was assessed
      using c-fos, JunB, and c-Jun expression in the guinea pig IMG and colonic
      myenteric plexus during mechanosensory stimulation and acute colitis in normal
      and capsaicin-treated animals. Intracolonic saline or 2% acetic acid was
      administered, and mechanosensory stimulation was performed by passage of a small
      (0.5 cm) balloon either 4 or 24 hr later. Lower doses of capsaicin or vehicle
      were used to activate primary afferent fibers during balloon passage. c-Jun did
      not respond to any of the stimuli in the study. c-fos and JunB were absent from
      the IMG and myenteric plexus of untreated and saline-treated animals. Acetic acid
      induced acute colitis by 4 hr, which persisted for 24 hr, but c-fos was found
      only in enteric glia in the myenteric plexus and was absent from the IMG. Balloon
      passage induced c-fos and JunB in only a small subset of IMG neurons and no
      myenteric neurons. However, balloon passage induced c-fos and JunB in IMG neurons
      (notably those containing somatostatin) and the myenteric plexus of acetic acid
      treated animals. After capsaicin treatment, c-fos and JunB induction by balloon
      passage was inhibited in the IMG, but there was enhanced c-fos expression in the
      myenteric plexus. c-fos and JunB induction by balloon stimulation was also
      mimicked by acute activation of capsaicin-sensitive nerves. These data suggest
      that colitis enhances reflex activity of the IMG by a mechanism that involves
      activation of both primary afferent fibers and the myenteric plexus.

PMID- 10087088
TI  - Network oscillations generated by balancing graded asymmetric reciprocal
      inhibition in passive neurons.
AB  - We describe a novel mechanism by which network oscillations can arise from
      reciprocal inhibitory connections between two entirely passive neurons. The model
      was inspired by the activation of the gastric mill rhythm in the crab
      stomatogastric ganglion by the modulatory commissural ganglion neuron 1 (MCN1),
      but it is studied here in general terms. One model neuron has a linear current
      voltage (I-V) curve with a low (L) resting potential, and the second model neuron
      has a linear current-voltage curve with a high (H) resting potential. The
      inhibitory connections between them are graded. There is an extrinsic modulatory
      excitatory input to the L neuron, and the L neuron presynaptically inhibits the
      modulatory neuron. Activation of the extrinsic modulatory neuron elicits stable
      network oscillations in which the L and H neurons are active in alternation. The
      oscillations arise because the graded reciprocal synapses create the equivalent
      of a negative-slope conductance region in the I-V curves for the cells.
      Geometrical methods are used to analyze the properties of and the mechanism
      underlying these network oscillations.

PMID- 10087089
TI  - The magnitude and phase of temporal modulation transfer functions in cat auditory
      cortex.
AB  - Temporal modulation transfer functions (tMTFs) in response to periodic click
      trains are presented for simultaneous recordings from primary auditory cortex,
      anterior auditory field, and secondary auditory cortex in 21 cats. The multiunit
      records could be separated in to 215 single-unit spike trains that allowed a
      reliable estimate of a group delay, which represents the cumulative delay for
      responses to repetitive stimuli. For approximately two-thirds of the 215 single
      units the group delay was within 7.5 msec of the response latency to the first
      clicks in the trains. For the remaining units, the group delay was on average
      approximately 14 msec higher, and this may result from differences in synaptic
      properties. These findings were similar in the three cortical areas studied. The
      findings are modeled based on presynaptic facilitation and depression and
      pyramidal cell calcium kinetics, and a quantitative description of the magnitude
      of the tMTF was obtained that resulted in substantially shorter depression time
      constants (20 msec) than reported for visual cortex (300 msec). A small amount (0
      5.5%) of facilitation that decayed with a time constant of 60 msec was obtained.
      Auditory cortical cells apparently have much faster recovery mechanisms than
      visual cortical cells. This allows for the ability of the auditory cortex to
      reliably track the rhythms that occur in natural sounds.

PMID- 10087090
TI  - Parallel information processing in the dorsal striatum: relation to hippocampal
      function.
AB  - We investigated the effects of localized medial and lateral CPu lesions and
      fornix/fimbria lesions on responses to a local cue and to behavior based on
      cognitive-spatial information in the water maze. Rats were trained concurrently
      on the cue (visible platform) and spatial (submerged platform) components of the
      task, followed by a test in which responses to the two types of information were
      dissociated by a measure of competing response tendencies. Bilateral lesions of
      lateral CPu did not affect acquisition of either cue or spatial responding but
      produced a preference for the spatial response on the competition test. Bilateral
      lesions of the medial CPu retarded but did not prevent learning both components
      and produced a preference for the cue response on the competition test. The
      latter effect was accompanied by increased thigmotaxis (swimming in the periphery
      of the pool), primarily during the early acquisition trials, which was attributed
      to an impaired ability to respond to learned spatial information. Fornix/fimbria
      lesions prevented spatial but not cue learning and produced a preference for the
      cue response on the competition test. Asymmetric lesions (unilateral hippocampus
      and contralateral medial CPu) produced mild retardation of acquisition of both
      the cue and spatial tasks and a preference for the cue response on the
      competition test. These findings dissociate the functions of the lateral and
      medial CPu and suggest that the hippocampus and medial CPu may be parts of a
      system that promotes responding based on learned cognitive-spatial information,
      particularly in competitive cue-place response situations.

PMID- 10087091
TI  - Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between
      the immune and nervous systems?
AB  - Intraperitoneal administration of the cytokine interleukin-1beta (IL-1beta)
      induces brain-mediated sickness symptoms that can be blocked by subdiaphragmatic
      vagotomy. Intraperitoneal IL-1beta also induces expression of the activation
      marker c-fos in vagal primary afferent neurons, suggesting that IL-1beta is a key
      component of vagally mediated immune-to-brain communication. The cellular sources
      of IL-1beta activating the vagus are unknown, but may reside in either blood or
      in the vagus nerve itself. We assayed IL-1beta protein after intraperitoneal
      endotoxin [lipopolysaccharide (LPS)] injection in abdominal vagus nerve, using
      both an ELISA and immunohistochemistry, and in blood plasma using ELISA. IL-1beta
      levels in abdominal vagus nerve increased by 45 min after LPS administration and
      were robust by 60 min. Plasma IL-1beta levels increased by 60 min, whereas little
      IL-1beta was detected in cervical vagus or sciatic nerve. IL-1beta
      immunoreactivity (IR) was expressed in dendritic cells and macrophages within
      connective tissues associated with the abdominal vagus by 45 min after
      intraperitoneal LPS injection. By 60 min, some immune cells located within the
      nerve and vagal paraganglia also expressed IL-1beta-IR. Thus, intraperitoneal LPS
      induced IL-1beta protein within the vagus in a time-frame consistent with
      signaling of immune activation. These results suggest a novel mechanism by which
      IL-1beta may serve as a molecular link between the immune system and vagus nerve,
      and thus the CNS.

PMID- 10087092
TI  - A neurocomputational theory of the dopaminergic modulation of working memory
      functions.
AB  - The dopaminergic modulation of neural activity in the prefrontal cortex (PFC) is
      essential for working memory. Delay-activity in the PFC in working memory tasks
      persists even if interfering stimuli intervene between the presentation of the
      sample and the target stimulus. Here, the hypothesis is put forward that the
      functional role of dopamine in working memory processing is to stabilize active
      neural representations in the PFC network and thereby to protect goal-related
      delay-activity against interfering stimuli. To test this hypothesis, we examined
      the reported dopamine-induced changes in several biophysical properties of PFC
      neurons to determine whether they could fulfill this function. An attractor
      network model consisting of model neurons was devised in which the empirically
      observed effects of dopamine on synaptic and voltage-gated membrane conductances
      could be represented in a biophysically realistic manner. In the model, the
      dopamine-induced enhancement of the persistent Na+ and reduction of the slowly
      inactivating K+ current increased firing of the delay-active neurons, thereby
      increasing inhibitory feedback and thus reducing activity of the "background"
      neurons. Furthermore, the dopamine-induced reduction of EPSP sizes and a
      dendritic Ca2+ current diminished the impact of intervening stimuli on current
      network activity. In this manner, dopaminergic effects indeed acted to stabilize
      current delay-activity. Working memory deficits observed after supranormal D1
      receptor stimulation could also be explained within this framework. Thus, the
      model offers a mechanistic explanation for the behavioral deficits observed after
      blockade or after supranormal stimulation of dopamine receptors in the PFC and,
      in addition, makes some specific empirical predictions.

PMID- 10087093
TI  - Central neuronal circuit innervating the lordosis-producing muscles defined by
      transneuronal transport of pseudorabies virus.
AB  - The lordosis reflex is a hormone-dependent behavior displayed by female rats
      during mating. This study used the transneuronal tracer pseudorabies virus (PRV)
      to investigate the CNS network that controls the lumbar epaxial muscles that
      produce this posture. After PRV was injected into lumbar epaxial muscles, the
      time course analysis of CNS viral infection showed progressively more PRV-labeled
      neurons in higher brain structures after longer survival times. In particular,
      the medullary reticular formation, periaqueductal gray (PAG), and ventromedial
      nucleus of the hypothalamus (VMN) were sequentially labeled with PRV, which
      supports the proposed hierarchical network of lordosis control. Closer inspection
      of the PRV-immunoreactive neurons in the PAG revealed a marked preponderance of
      spheroid neurons, rather than fusiform or triangular morphologies. Furthermore,
      PRV-immunoreactive neurons were concentrated in the ventrolateral column, rather
      than the dorsal, dorsolateral, or lateral columns of the PAG. Localization of the
      PRV-labeled neurons in the VMN indicated that the majority were located in the
      ventrolateral subdivision, although some were also in other subdivisions of the
      VMN. As expected, labeled cells also were found in areas traditionally associated
      with sympathetic outflow to blood vessels and motor pathways, including the
      intermediolateral nucleus of the spinal cord, the paraventricular hypothalamic
      nucleus, the red nucleus, and the motor cortex. These results suggest that the
      various brain regions along the neuraxis previously implicated in the lordosis
      reflex are indeed serially connected.

PMID- 10087094
TI  - Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and
      autonomic stress responses in rats.
AB  - The medial prefrontal cortex (mPFC) is highly activated by stress and modulates
      neuroendocrine and autonomic function. Dopaminergic inputs to mPFC facilitate
      coping ability and demonstrate considerable hemispheric functional
      lateralization. The present study investigated the potentially lateralized
      regulation of stress responses at the level of mPFC output neurons, using
      ibotenic acid lesions. Neuroendocrine function was assessed by plasma
      corticosterone increases in response to acute or repeated 20 min restraint
      stress. The primary index of autonomic activation was gastric ulcer development
      during a separate cold restraint stress. Restraint-induced defecation was also
      monitored. Plasma corticosterone levels were markedly lower in response to
      repeated versus acute restraint stress. In acutely restrained animals, right or
      bilateral, but not left mPFC lesions, decreased prestress corticosterone levels,
      whereas in repeatedly restrained rats, the same lesions significantly reduced the
      peak stress-induced corticosterone response. Stress ulcer development (after a
      single cold restraint stress) was greatly reduced by either right or bilateral
      mPFC lesions but was unaffected by left lesions. Restraint-induced defecation was
      elevated in animals with left mPFC lesions. Finally, a left-biased asymmetry in
      adrenal gland weights was observed across animals, which was unaffected by mPFC
      lesions. The results suggest that mPFC output neurons demonstrate an intrinsic
      right brain specialization in both neuroendocrine and autonomic activation. Such
      findings may be particularly relevant to clinical depression which is associated
      with both disturbances in stress regulatory systems and hemispheric imbalances in
      prefrontal function.

PMID- 10087096
TI  - Management of skull base chordoma.
AB  - Two management modal-ities appear to be important in treating skull base
      chordomas: surgery and radiation therapy. Radical resection of lesions of the
      distal sacrum (S3-S5) and coccyx may be curative, as total removal is often
      achieved. In contrast, complete resection of chordomas of the base of the skull
      is rarely successful because of the inability to achieve a true complete surgical
      resection. On the other hand, treatment of skull base chordomas by radiation
      therapy alone is often difficult owing to the large size of the lesion and the
      dose limitation imposed by the sensitivity of the adjacent structures. Local
      relapse is the predominant type of treatment failure of skull base chordoma.
      Skull base surgery and radiation therapy have significantly improved over the
      last 20 years. The following papers review the most significant recent analyses
      of therapeutic options in treating skull base chordomas. It seems that the
      combination of aggressive surgery followed by combined proton-photon radiation
      therapy offers the best chance of long-term local control to patients harboring
      cranial chordomas.

PMID- 10087097
TI  - Technological advances in the surgical management of trigeminal neuralgia.
AB  - For years, many controversies have arisen on the surgical management of
      trigeminal neuralgia and neuropathy. The purpose of this paper is to review most
      of the current surgical techniques for the management of trigeminal neuralgia and
      present our position on the current management of these situations.

PMID- 10087098
TI  - Epidemiological features and diagnostic evaluation of intracranial aneurysms.
AB  - Female gender and cigarette smoking appear to be risk factors for the development
      of multiple intracranial aneurysms. An acquired nature is likely in this form.
      The mechanism of aneurysm formation in patients with sickle cell anemia is
      apparently different. These patients also present multiple aneurysms that show
      propensity for vertebrobasilar territory and appear at a younger age. Familial
      cerebral aneurysms are diagnosed once heritable connective tissue disorders have
      been excluded. The age of patients tends to be lower and the size of aneurysm to
      be smaller at the time of rupture in the familial form. These aneurysms are less
      frequently found in the anterior communicating artery than the sporadic
      aneurysms. A high incidence of asymptomatic familial aneurysms was detected in
      people with family histories of intracranial aneurysms studied by means of
      magnetic resonance angiography. Furthermore, familial aneurysms are more likely
      to rupture in families having members with aneurysmal subarachnoid hemorrhage
      (SAH) than in those without. The results of an interesting study using color
      "power" transcranial Doppler ultrasound in patients with aneurysmal SAH suggest
      that as the intracranial pressure diminished, the size of the aneurysm increased,
      and there was relatively little change between maximum and minimum dimensions
      during the cardiac cycle, i.e., the pulsatility is reduced. The use of
      postoperative angiography after clipping is a matter of debate. The indication
      more widely accepted is in large aneurysms with a wide neck, in which incomplete
      clipping can be suspected. Taking into account the current low risk of
      angiography in centers of excellence, its routine use may be recommended.
      Aneurysm remnants, vessel occlusion, vasospasm, and newly identified aneurysms
      are the main findings that were reported.

PMID- 10087099
TI  - What determines the risk of hemorrhage from cerebral arteriovenous malformations?
AB  - We reviewed seven recent articles that discuss the risk factors associated with
      the hemorrhagic presentation of cerebral arteriovenous malformations (AVMs).
      Although several such factors have been identified, only nine have been shown to
      be independent predictors of AVM hemorrhage by multiple logistic regression. All
      of the studies reviewed are subject to biases that compromise their ability to
      identify risk factors for hemorrhage confidently. A prospective, multicenter,
      controlled trial would be necessary to identify such risk factors with certainty.

PMID- 10087100
TI  - Lesion-making surgery versus brain stimulation for treatment of Parkinson's
      disease.
AB  - With the resurgence of interest in neurosurgical intervention for the treatment
      of drug-resistant Parkinson's disease, posteroventral pallidotomy (internal
      globus pallidus) has become a procedure widely applied by neurosurgeons. In
      chronic deep brain stimulation, the stimulation target is the same area as the
      above lesion-making point: the ventralis intermedius thalamic nucleus,
      subthalamic nucleus, and internal globus pallidus, since deep brain stimulation
      does not induce brain damage, and it is possible to control the stimulation
      (frequency and strength). There is also no recurrence. This procedure has the
      reversibility, selectivity, and adjustability that is ideal for functional
      neurosurgery. Such chronic stimulation therapy has thus now become an alternative
      to lesion-making stereotactic surgery. However, stimulation therapy directed at a
      particular target has more specific effects on particular symptoms of Parkinson's
      disease, so that an effective stimulation target needs to be selected depending
      on the nature of the syndrome to be improved. This article presents a review of
      the most recent reports on how to perform safer and more effective pallidotomy,
      and of recent basic and clinical reports concerning pallidal stimulation. Some
      answers to the question of whether or not stimulation therapy is an alternative
      to lesion-making surgery at the internal globus pallidus to improve parkinsonian
      syndrome and levodopa-induced dyskinesias are discussed.

PMID- 10087101
TI  - Radiosurgery: an effective treatment for cavernous sinus meningiomas?
AB  - Meningiomas involving the cavernous sinus present the neurosurgeon with different
      choices: observation, microsurgery, or radiosurgery. During the last decade,
      advances in microsurgical techniques have significantly lowered the treatment
      related morbidity, and some neurosurgeons have reported long-term follow-up
      results. Recently, several radiosurgical series have reported excellent tumor
      control and good functional preservation for tumors in this area. Most of these
      series do not provide complete information about the patient's cranial nerve
      function, and objective and subjective outcome data. The follow-up provided has
      also been short, considering that meningiomas have a tendency to recur or regrow
      up to 20 years postoperatively. There is also the concern about those patients
      who fail radiosurgical treatment, since microsurgery does not yield good results
      in such cases. In this paper, several radiosurgical series are critically
      reviewed, with a discussion about the pros and cons of microsurgery versus
      radiosurgery. The authors suggest that a uniform reporting strategy be adopted by
      all surgeons treating tumors of this area, which will allow comparative studies
      to be conducted. Additionally, we suggest a treatment algorithm for cavernous
      sinus meningiomas, based on the patients age, occupation and preference,
      preoperative binocular function, and curability of the tumor.

PMID- 10087104
TI  - Papers reviewed in this issue.

PMID- 10087105
TI  - Publications scanned for pertinent articles.

PMID- 10087102
TI  - Dysembryoplastic neuroepithelial tumor.
AB  - Dysembryoplastic neuroepithelial tumors (DNTs) were first described in 1988. A
      DNT is a cortical tumor that produces enlargement of a gyrus, forming a megagyrus
      that exceeds the normal thickness of the cortex. This tumor is generally seen in
      young patients with a long-standing history of drug-resistant and disabling
      seizures mostly of the complex partial type. No neurological deficits are found
      between the interictal periods in the majority of the reported cases. A general
      agreement exists over the clinical and radiological manifestations of a DNT as
      well as the benign biological behavior. Two pathological variants of DNT have
      been recognized: the single form, composed only of the so-called specific
      glioneuronal element, and the complex form that additionally shows glial nodules
      and foci of cortical dysplasia. Nevertheless, and despite the benign biological
      course, nuclear atypias, cellular monstruosities, foci of necrosis and mitosis
      can also be found. Surgical eradication of the tumor will usuallly have a good
      prognosis, without recurrences and with a positive control to seizure-free
      clinical outcome. Controversy continues to exist over a hamartomatous or a
      neoplastic origin of this lesion. The DNT has been placed among the neuronal and
      mixed neuronal-glial neoplasms in the revised World Health Organization (WHO)
      brain tumor classification, a category that includes the gangliogliomas and the
      central neurocytomas. Ultrastructural studies and immunostaining techniques may
      suggest that these three lesions represent different spectrums of the same
      condition. This paper reviews the most recent publications to offer a better
      understanding of DNTs and their implications in diagnosis and management.

PMID- 10087106
TI  - Imaging pulmonary disease in AIDS: state of the art.
AB  - The spectrum of pulmonary diseases in AIDS including infections and neoplasms
      that affect the lungs are reviewed. Characteristic plain film and CT findings are
      illustrated.

PMID- 10087107
TI  - Usefulness of morphological characteristics for the differentiation of benign
      from malignant solitary pulmonary lesions using HRCT.
AB  - The aim of this study was to analyze different characteristics on high-resolution
      computed tomography (HRCT) that help differentiate benign solitary pulmonary
      lesions (BSPLs) from malignant solitary pulmonary lesions (MSPLs). High
      resolution computed tomography was performed on 104 consecutive patients with
      SPLs. The whole lesion was examined with a slice thickness of 1 mm and a 12-cm
      field of view. All lesions were surgically excised within 24 h of the CT
      examination. Satellite nodules, cavitations, and necrosis were found only in
      MSPLs. Useful characteristics for the differentiation of BSPLs from MSPLs were
      the presence of spicules (p < 0.00005), spicules extending to the visceral pleura
      (p < 0.0005), the vessel sign (p < 0.0005), pleural retraction (p < 0.001),
      circumscribed pleural thickening (p < 0.001), the bronchus sign (p < 0.005), the
      presence of ground-glass attenuation adjacent to the SPL (p < 0.01), the density
      of the lesion (p < 0.05), and the length of spicules (p < 0.05). Using the
      significant characteristics p < 0.01 for the identification of MSPLs, a
      sensitivity of 91.4 % and a specificity of 56.5 % (accuracy of 83.7 %) was found.
      A precise morphological assessment of the periphery of the pulmonary lesion is
      necessary. The HRCT technique is useful in differentiation of BSPLs from MSPLs.
      However, metastases strongly resembled benign lesions in terms of size and edge
      type, and chronic inflammatory pseudotumors as a group mimic MSPLs.

PMID- 10087108
TI  - Time-resolved MR angiography of the upper abdomen: initial clinical experience.
AB  - In this study, thirty-eight patients with a variety of upper abdominal diseases
      were examined with three-dimensional time-resolved MR angiography (7 sec/data
      set). Visualisation of arterial and venous anatomy was excellent in the majority
      of patients. Moreover, subtraction images could be calculated and organ perfusion
      could be assessed. It is concluded that this technique opens new perspectives for
      a comprehensive evaluation of vascular and parenchymal disease.

PMID- 10087109
TI  - Pseudoaneurysm of the superficial femoral artery following accidental trauma:
      result of treatment by percutaneous stent-graft placement.
AB  - Accidental trauma frequently involves the extremities, and can extend to involve
      their blood supply, causing exsanguinating hemorrhage and pseudoaneurysm in the
      involved blood vessel. This is traditionally managed by surgical repair. We
      report a case in which control of life-threatening hemorrhage and exclusion of a
      large, post-traumatic pseudoaneurysm in the superficial femoral artery was
      performed by a commercially available stent-graft, without complication. This
      treatment method may be a safe and effective alternative to surgery in selected
      patients.

PMID- 10087110
TI  - Scrotal arteriovenous malformation and its preoperative embolization.
AB  - Arteriovenous malformations of the scrotum are extremely rare. A case of scrotal
      arteriovenous malformation and its preoperative embolization in a child is
      presented.

PMID- 10087111
TI  - Focal liver lesions: Doppler ultrasound.
AB  - Echo patterns of focal liver lesions as well as other morphological criteria do
      not suffice for differential diagnosis. In an attempt to increase the specificity
      of ultrasound of focal liver lesions, several years of Doppler-flow information
      was evaluated. Recent advances in ultrasound technology (power Doppler imaging,
      second harmonic imaging) as well as commercial availability of an intravenous
      signal enhancer (contrast agent) have additionally improved results of this
      technique.

PMID- 10087112
TI  - High-resolution magnetic resonance imaging of the anal sphincter using a
      dedicated endoanal receiver coil.
AB  - The use of a surface coil in MR imaging improves signal-to-noise ratio of
      adjacent tissues of interest. We therefore devised an endoanal receiver coil for
      imaging the anal sphincter. The probe is solid and re-usable: it comprises a
      saddle geometry receiver with integral tuning, matching and decoupling. It is
      placed in the anal canal and immobilised externally. Both in vitro and in vivo
      normal anatomy is identified. The mucosa is high signal intensity, the submucosa
      low signal intensity, the internal sphincter uniformly high signal intensity and
      the external sphincter low signal intensity on T1- and T2-weighted images. In
      females, the transverse perineal muscle bridges the inferior part of the external
      sphincter anteriorly. In perianal sepsis, collections and the site of the
      endoanal opening are identified. In early-onset fecal incontinence following
      obstetric trauma/surgery, focal sphincter defects are demonstrated; in late-onset
      fecal incontinence external sphincter atrophy is seen. In fecally incontinent
      patients with scleroderma, forward deviation of the anterior sphincter
      musculature with descent of rectal air and feces into the anal canal is noted.
      The extent of sphincter invasion is assessed in low rectal tumours. In children
      with congenital anorectal anomalies, abnormalities of the muscle components are
      defined using smaller-diameter coils. Such information is invaluable in the
      assessment and surgical planning of patients with a variety of anorectal
      pathologies.

PMID- 10087113
TI  - Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement
      after mangafodipir trisodium injection on MR imaging.
AB  - The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)
      enhanced MR imaging in differentiating malignant from benign hepatocellular
      tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six
      with focal nodular hyperplasias, and one with a single hepatocellular adenoma
      were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h
      after, and 24 h after intravenous injection of Mn-DPDP (5 micromol/kg).
      Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise
      ratio, and qualitative analysis including the presence of a central area and a
      capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was
      observed in all the tumors with significant improvement (p < 0.05) in contrast-to
      noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There
      were no significant differences in the mean enhancement and the mean contrast-to
      noise ratio (CNR) between benign and malignant tumors. No enhancement was seen
      within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal
      nodular hyperplasias, and within capsules which were observed in 9 hepatocellular
      carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant
      tumors but did not enable differentiation between benign and malignant tumors of
      hepatocellular nature.

PMID- 10087114
TI  - Defecography: does parity play a role in the development of rectal prolapse?
AB  - Few studies related to parity address the changes in anorectal function in women.
      Since the majority of patients with rectal prolapse are women, we undertook this
      study to assess the role of parity in the development of rectal prolapse. We
      retrospectively reviewed defecography studies performed on 354 female patients
      over a 10-year period. Studies noting the presence of intra-anal and external
      rectal prolapse (full thickness protrusion of the rectum into and through the
      anal sphincter) were reviewed. Cases with intrarectal or hidden rectal prolapse,
      a condition of lesser clinical importance, were excluded. The obstetric histories
      of the patients with rectal prolapse (n = 27) were compared to those of patients
      without rectal prolapse (n = 88). There was a larger proportion of nulliparous
      women in the rectal prolapse group than in the group without rectal prolapse,
      suggesting that factors in addition to parity play a role in the development of
      rectal prolapse. However, parous women with rectal prolapse had delivered
      significantly more children (3.3) than parous women without prolapse (2.5) (P =
      0.03). The exact cause of rectal prolapse remains unclear. Childbearing appears
      to play a limited role in its pathogenesis since nulliparous women are also at
      risk of developing rectal prolapse.

PMID- 10087115
TI  - Hemorrhagic necrosis due to peliosis hepatis: imaging findings and pathological
      correlation.
AB  - Peliosis hepatis is an uncommon liver condition characterized by blood-filled
      cavities. We report the CT, angiographic and MR features of a case of peliosis
      hepatis with no obvious etiology and spontaneously regressing hemorrhagic
      necrosis. Helical CT showed multiple peripheral low-density regions with foci of
      spontaneous high density suggesting the presence of blood component. On MR
      imaging, the multiple peripheral lesions were hypointense on T1-weighted and
      hyperdense on T2-weighted images, with bright foci on all sequences suggesting
      subacute blood. Angiography showed no evidence of tumor or vascular malformation;
      multiple nodular vascular lesions filling in the parenchymal phase and persisting
      in the venous phase suggested blood-filled cavities. Pathological examination
      showed blood-filled spaces with no endothelial lining, characteristic of the
      parenchymal type of peliosis. Knowledge of the imaging features of hemorrhagic
      necrosis due to peliosis hepatis is important since it can be responsive to
      antibiotic therapy. Furthermore, differentiating hemorrhagic necrosis from
      hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

PMID- 10087116
TI  - Pseudomyxoma retroperitonei.
AB  - We report a rare case of pseudomyxoma retroperitonei in a 58-year-old woman with
      a past history of severe appendicitis. The imaging showed a multicystic mass
      similar to pseudomyxoma peritonei, but the tumor was located in the
      retroperitoneal space.

PMID- 10087117
TI  - Tumour characteristics and survival in patients with invasive interval breast
      cancer classified according to mammographic findings at the latest screening: a
      comparison of true interval and missed interval cancers.
AB  - The aim of this study was to investigate whether different mammographic
      categories of interval cancer classified according to findings at the latest
      screening are associated with different distributions of prognostic factors or
      with different survival rates. The series consisted of all patients with invasive
      interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were
      evaluated with regard to age, radiological category, interval between the latest
      screen and diagnosis and tumour characteristics at the time of diagnosis. We
      investigated possible relationships between the survival rate of patients with
      interval cancer and the interval between the latest screen and diagnosis, tumour
      characteristics and radiological category of the interval tumours. The study
      focused on comparison of patients with true interval and missed interval cancer.
      Women with mammographically occult tumours were younger than those in the other
      radiological categories. Comparisons of true interval cancers with overlooked or
      misinterpreted tumours showed equal distributions of age, tumour size, TNM stage
      and lymph node status. The overlooked or misinterpreted tumours showed
      significantly higher proportions of grade-I tumours (22 vs 11 %), tumours with
      low S-phase fraction (SPF; 44 vs 24 %) and oestrogen receptor (ER) positive
      tumours (72 vs 57 %). However, analyses of survival rates disclosed no clear
      differences between the two radiological categories. Radiological category and
      interval between the latest screen and diagnosis were not genuine predictors of
      the prognosis in patients with invasive interval breast cancer. No certain
      prognostic difference existed between true interval cancers and overlooked or
      misinterpreted interval breast cancers, despite higher proportions of grade-I
      tumours, ER positive tumours and tumours with low SPF in the latter group.

PMID- 10087118
TI  - MRI of the breast in patients with metastatic disease of unknown primary.
AB  - The objective of this study was to assess the value of contrast-enhanced dynamic
      breast imaging in patients with carcinoma of unknown primary (CUP). Fourteen
      patients presenting with metastatic disease compatible with breast cancer
      (axillary lymph node metastasis: n = 6; supraclavicular lymph node metastasis: n
      = 1; bone metastasis: n = 3; liver metastasis: n = 3; lung metastasis: n = 1),
      who had no evidence of tumor in X-ray mammograms and ultrasound, underwent
      bilateral dynamic breast MR imaging. Suspicious lesions were localized
      preoperatively using a stereotactic device for MR-guided localization procedures.
      Magnetic resonance imaging revealed suspicious lesions in 9 of 14 patients.
      Histopathology revealed invasive carcinoma of the breast in 6 of these patients.
      Two enhancing lesions were fibroadenomas; one proved to be sclerosing adenosis.
      In 5 patients MR imaging showed no abnormality. Follow-ups performed up to 1 year
      after initial treatment revealed no breast cancers in these 5 patients. In
      patients with metastatic disease of unknown primary, MRI of the breast depicts
      the primary in a considerable number of cases with normal conventional
      evaluation.

PMID- 10087119
TI  - Abdominal ultrasound findings in children with hemophagocytic
      lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis, a variant of histiocytosis, is characterized
      by an uncontrolled activation of the cellular immune system, including hepatic
      mononuclear phagocytic cells. Abdominal ultrasound findings in children are
      evaluated in this disease. We present six pediatric cases, two with familial and
      four with sporadic hemophagocytic lymphohistiocytosis, examined by abdominal
      sonography. Three signs were frequently observed: thickening of the gallbladder
      wall (all cases), increased periportal echogenicity (four cases), and enlarged
      lymph nodes in the porta hepatis (four cases). Hepatomegaly, splenomegaly, and
      ascitic fluid may also be found. These imaging findings are not specific and may
      be seen in viral hepatitis. However, once hepatitis is excluded, they may suggest
      the diagnosis of hemophagocytic lymphohistiocytosis in a critically ill child. A
      bone smear must be done to establish the diagnosis.

PMID- 10087120
TI  - Esophageal duplication cyst coexisting with Bochdalek's hernia and polysplenia.
AB  - Esophageal duplication cyst, Bochdalek's hernia and polysplenia are uncommon
      congenital anomalies which have not been reported to be associated with each
      other. We present the radiological aspects of an unusual coexistence of these
      three congenital anomalies in a 4-month-old girl.

PMID- 10087121
TI  - An accessory ossification centre in the calcaneus with talonavicular and second
      metatarsocuneiform coalitions.
AB  - We present the case of an 11-year-old girl with an accessory ossification centre
      of the calcaneus with talonavicular and second metatarsocuneiform coalitions, and
      bilateral os tibiale externum.

PMID- 10087122
TI  - Bilateral extra tarsal bones in Rubinstein-Taybi syndrome: the fourth cuneiform
      bones.
AB  - Rubinstein-Taybi syndrome is a syndrome of mental retardation associated with
      digital changes, consisting mainly of broad thumbs and large toes. This paper
      deals with pedal changes in a patient with this syndrome in whom bilateral,
      large, extra tarsal bones occurred between the medial cuneiform and intermediate
      cuneiform bones. They articulated with these bones, as well as with the first and
      the second metatarsals. It is suggested that these extra tarsal bones be labelled
      as the fourth cuneiform bones (os cuneiformis IV). To the best of the author's
      knowledge, such an extra tarsal bone has never been reported in humans or other
      mammalians. One could speculate that they originated from bilateral extra
      ossification centers or from an isolated, accelerated ossification and extreme
      enlargement of the so-called os intercuneiforme, a supernumerary ossicle, in this
      patient with Rubinstein-Taybi syndrome.

PMID- 10087123
TI  - Pulmonary anthracosis in children.
AB  - We report two cases of children with malignancies and subpleural nodules found on
      computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This
      pathologic condition has never been reported in children. Causes of anthracosis
      include a smoking environment, living in urban areas and air pollution.

PMID- 10087124
TI  - Interactive MR-guided biopsies of maxillary and skull-base lesions in an open-MR
      system: first clinical results.
AB  - The purpose of this study was to explore the potential of interactive MR-guided
      biopsies in the maxillary and skull base region using a 0.5-T open-configuration
      scanner in patients with tumours affecting the maxilla or skull base. Ten
      patients with cystic or solid tumours affecting the maxillary and skull base
      regions underwent MR-guided biopsy in a superconducting, open 0.5-T MR system
      equipped with an optical frameless stereotaxic system. T2-weighted spin-echo
      images were acquired prior to and following biopsy, which was performed with 18-
      or 22-G needles using an enoral or percutaneous approach following infiltration
      of the skin, mucosa and periosteum with local anaesthetics. The position of the
      needle tip was continuously updated on fast T1-weighted gradient-recalled-echo
      images (TR 19 ms, TE 7.1 ms, flip angle 30 degrees, slice thickness 1 cm, field
      of view 24 x 24 cm) using the frameless stereotaxic system. In addition, the
      needle was identified based on the associated susceptibility artefact in all
      three planes. Once the target lesion had been reached, cytology material was
      aspirated. All ten patients tolerated the interactive MR-guided biopsies well
      without complications. Vital structures, including the brain, neurovascular
      bundles, vessels and eyes, were visualized on MR imaging and could be spared.
      There was no difference in the use of 18- or 22-G non-ferromagnetic needles
      concerning the susceptibility artefact. Sufficient material for cytological
      analysis was obtained in nine of ten cases. The mean biopsy time was 15 min.
      Interactive MR-guided biopsies of the head and neck in an open system are
      technically feasible and safe. Monitoring of the needle path in multiple planes
      permits the interactive adjustment of the needle course in near real time.
      Interactive MR-guided biopsies may well replace open surgical procedures in the
      maxillary region in selected patients.

PMID- 10087125
TI  - MR contribution in surgery of epilepsy.
AB  - The contribution of MR imaging in patients with drug-resistant epilepsy
      considered for surgical therapy is discussed. In this review we focus on: (a)
      focal abnormalities (mesial temporal sclerosis, focal migration disorders,
      hamartomatous lesions and low-grade tumours, phakomatosis and vascular
      malformations) associated with therapy-resistant partial epilepsy, requiring
      resective surgery; (b) abnormalities leading to generalized seizures that require
      more drastic surgical procedures, such as callosotomy and functional
      hemispherectomy; and (c) localisation of implanted depth-electrodes.

PMID- 10087126
TI  - Kinematic CT and MR imaging of the patellofemoral joint.
AB  - Anterior knee pain is a frequently encountered orthopedic symptom and is often
      associated with patellofemoral malalignment, which may cause chondromalacia of
      the patella. The difficulty in determining the patellar position between 0
      degrees and 30 degrees of knee flexion with a conventional axial radiographic
      examination is well known. The introduction of computed tomography (CT) and
      magnetic resonance (MR) imaging for the diagnosis of knee joint abnormalities has
      enabled assessment of the patellar position in this critical range. More
      recently, emphasis has been placed on dynamic visualization of patellar motion to
      detect an abnormal tracking pattern. The important influence of the quadriceps
      muscle on the patellar tracking pattern is well known and has been examined
      during active knee extension by the use of ultrafast CT, and motion-triggered and
      ultrafast MR imaging. This article provides an overview of the current status of
      kinematic CT and MR imaging in the diagnosis of patellofemoral alignment, its
      clinical implications, and future directions.

PMID- 10087127
TI  - Injuries of the lateral collateral ligaments of the ankle: assessment with MR
      imaging.
AB  - The aim of this study was to evaluate the ability of MRI to display injuries of
      the lateral collateral ligamentous complex in patients with an acute ankle
      distorsion trauma. The MR examinations of 36 patients with ankle pain after ankle
      distorsion were evaluated retrospectively without knowledge of clinical history,
      outcome and/or operative findings. The examinations were performed on a 1. 5-T
      whole-body imager using a flexible surface coil. The signs for ligamentous
      abnormality were as follows: complete or partial discontinuity, increased signal
      within, and irregularity and waviness of the ligament. The results were compared
      with operative findings in 18 patients with subsequent surgical repair. Eighteen
      patients with conservative therapy had a follow-up MR examination after 3 months.
      There was 1 sprain, 3 partial and 32 complete tears of the anterior talofibular
      ligament, and 5 sprains, 5 partial, and 7 complete tears of the calcaneofibular
      ligament. There were no lesions of the posterior talofibular ligament. Compared
      with surgery, MRI demonstrated in 18 of 18 cases the exact extent of anterior
      talofibular ligament injuries and underestimated the extent in 2 of 8 cases of
      calcaneofibular ligament injury. In patients with follow-up MRI after
      conservative therapy, a thickened band-like structure was found along the course
      of the injured ligament in 17 of 18 cases. The absence of ligament repair after
      conservative treatment was confirmed during operative revision in one case. The
      MRI technique allows for grading of the extent of injury of the lateral
      collateral ligamentous complex after acute ankle strain. It seems to be suitable
      for monitoring the healing process after conservative-functional treatment of
      ligament tears.

PMID- 10087128
TI  - MRI findings of muscle involvement in idiopathic hypereosinophilic syndrome.
AB  - A 40-year-old white man presented with fever, muscle pain, skin nodules and
      persistent hypereosinophilia over a period of 1 year. In addition, he had
      ventricular arrhythmias with episodes of tachycardia. Besides a lack of response
      to antiparasitic therapy, laboratory and pathological data excluded the diagnosis
      of trichinosis or any other parasitic infection. The patient's course of the
      disease over the previous 1(1)/2 years was compatible with hypereosinophilic
      syndrome. In a muscle biopsy several eosinophilic perivascular and leucocytic
      intravascular infiltrates were found, indicative of muscle involvement by the
      disease. This is a report on the MRI findings of muscle involvement in idiopathic
      hypereosinophilic syndrome.

PMID- 10087129
TI  - Prostate specific antigen: an opinion on its value to the radiologist.
AB  - Screening for prostate cancer is controversial. There is currently enormous
      pressure from the public and media to test men for early prostate cancer, in a
      manner similar to the screening of women for breast cancer. Unfortunately,
      however, the two cancers do not behave in a similar biological manner; breast
      cancer screening has been shown to reduce mortality, but prostate cancer
      screening has not yet been proven to reduce mortality. Prostate-specific antigen
      (PSA) is currently the best single test for prostate cancer diagnosis, but it
      cannot identify whether the detected cancer will cause clinically significant
      disease. PSA can be used as an aid to the diagnosis, staging, prognosis and
      follow-up of patients with prostate cancer, and its use has transformed the
      diagnosis of cancer and has markedly improved the detection of organ-confined
      prostate cancer in Europe and North America. PSA is, however, an imperfect
      diagnostic marker, and a variety of approaches have been investigated in recent
      years to improve its specificity in the diagnosis of prostate cancer. These new
      approaches have been developed by urologists, radiologists and biochemists, and
      can be confusing for the clinician without special knowledge in this field. This
      article aims to review current knowledge of PSA from the viewpoint of the
      radiologist.

PMID- 10087130
TI  - Varicocele: strategies in diagnosis and treatment.
AB  - Varicocele can be very easily diagnosed by physical examination and subsequently
      treated when it is painful or associated with testicular hypotrophy. However,
      palpability of the spermatic vein and reflux in low grade or even questionable
      varicoceles can be difficult to assess without imaging modalities. This can be a
      common problem for all physicians treating hypofertile men to decide whether the
      varicele needs to be treated or not. However, a gold standard that defines the
      presence of a subclinical varicocele has not yet been established. The different
      diagnostic tools based on ultrasonography investigated these past years to define
      a flow reversal in incontinent spermatic veins are presented in the first part of
      this review, with emphasis on subclinical varicocele. In the second part, we
      present our experience, together with a review of the literature concerning
      embolization of the spermatic veins as an alternative to surgery to treat
      varicoceles.

PMID- 10087131
TI  - Spiral CT angiography of renal arteries: comparison with angiography.
AB  - A prospective study was carried out to determine the accuracy of spiral CT
      angiography (CTA) in the detection of renal artery stenosis (RAS). Eighty-two
      patients with arterial hypertension underwent CTA and digital subtraction
      angiography (DSA) to exclude RAS. For CTA a contrast medium bolus of 100-150 ml
      (flow rate 3 ml/s) was injected. A 24 or 40 s CTA was started at the origin of
      the superior mesenteric artery after a delay time determined by test bolus
      injection (collimation = 2 mm, pitch = 1/1.5). For stenosis detection transverse
      images supported by maximum intensity projections (MIP) or multiplanar
      reconstruction projections were used. Of 197 renal arteries examined (including
      33 accessory arteries), 34 RAS were visualized using DSA. With CTA, one
      hemodynamic RAS was missed and one additional hemodynamic RAS was found.
      Sensitivity/specificity was calculated to be 94 %/98 %. For hemodynamically
      relevant RAS (> 50 %) the sensitivity/specificity was 96 %/99 %. CTA additionally
      depicted five adrenal masses. The high accuracy rate of RAS detection thus allows
      the use of CTA as a screening method in patients with arterial hypertension to
      exclude a renovascular cause.

PMID- 10087132
TI  - MR imaging of a case of adenomatoid tumor of the adrenal gland.
AB  - The aim of this case report is to describe the appearance on magnetic resonance
      imaging (MRI) of an incidentally found adenomatoid tumor of the adrenal gland,
      and to evaluate the utility of MRI in characterizing this type of tumor. The
      appearance of the tumor was nonspecific on T1-weighted in-phase, opposed-phase,
      and T2-weighted images, as well as its behavior after paramagnetic contrast
      administration, outlining the differential diagnosis among carcinoma, metastatic
      tumors, and pheochromocytoma. After surgery, the pathologic diagnosis was
      adenomatoid benign tumor of mesothelial origin. Although MRI enables the
      characterization of most benign lesions of the adrenal gland, the appearance of
      other lesions is nonspecific. In our case, MRI did not assist in preoperative
      diagnosis, guiding us towards a diagnosis of malignancy.

PMID- 10087133
TI  - A PC program for estimating organ dose and effective dose values in computed
      tomography.
AB  - Dose values in CT are specified by the manufacturers for all CT systems and
      operating conditions in phantoms. It is not trivial, however, to derive dose
      values in patients from this information. Therefore, we have developed a PC-based
      program which calculates organ dose and effective dose values for arbitrary scan
      parameters and anatomical ranges. Values for primary radiation are derived from
      measurements or manufacturer specifications; values for scattered radiation are
      derived from Monte Carlo calculations tabulated for standard anthropomorphic
      phantoms. Based on these values, organ doses can be computed by the program for
      arbitrary scan protocols in conventional and in spiral CT. Effective dose values
      are also provided, both with ICRP 26 and ICRP 60 tissue-weighting coefficients.
      Results for several standard CT protocols are presented in tabular form in this
      paper. In addition, potential for dose reduction is demonstrated, for example, in
      spiral CT and in quantitative CT. Providing realistic patient dose estimates for
      arbitrary CT protocols is relevant both for the physician and the patient, and it
      is particularly useful for educational and training purposes. The program, called
      WinDose, is now in use at the Erlangen University hospitals (Germany) as an
      information tool for radiologists and patients. Further extensions are planned.

PMID- 10087134
TI  - Efficient object scatter correction algorithm for third and fourth generation CT
      scanners.
AB  - X-ray photons which are scattered inside the object slice and reach the detector
      array increase the detected signal and produce image artifacts as "cupping"
      effects in large objects and dark bands between regions of high attenuation. The
      artifact amplitudes increase with scanned volume or slice width. Object scatter
      can be reduced in third generation computed tomography (CT) geometry by
      collimating the detector elements. However, a correction can still improve image
      quality. For fourth generation CT geometry, only poor anti-scatter collimation is
      possible and a numeric correction is necessary. This paper presents a correction
      algorithm which can be parameterized for third and fourth generation CT geometry.
      The method requires low computational effort and allows flexible application to
      different body regions by simple parameter adjustments. The object scatter
      intensity which is subtracted from the measured signal is calculated with
      convolution of the weighted and windowed projection data with a spatially
      invariant "scatter convolution function". The scatter convolution function is
      approximated for the desired scanner geometry from pencil beam simulations and
      measurements using coherent and incoherent differential scatter cross section
      data. Several examples of phantom and medical objects scanned with third and
      fourth generation CT systems are discussed. In third generation scanners, scatter
      artifacts are effectively corrected. For fourth generation geometry with poor
      anti-scatter collimation, object scatter artifacts are strongly reduced.

PMID- 10087135
TI  - EUFORA mailing list: a European forum for radiologists.

PMID- 10087136
TI  - Spontaneous transethmoidal cerebrospinal fluid fistula associated with empty
      sella.

PMID- 10087137
TI  - Sacroiliac joint pneumatocysts: prevalence on CT examinations.

PMID- 10087138
TI  - Quiz case of the month. Lymphatic cyst of the mediastinum.

PMID- 10087139
TI  - On the mechanism of the enhancement of delayed rectifier K+ current by
      extracellular ATP in guinea-pig ventricular myocytes.
AB  - The effects of extracellular adenosine 5'-triphosphate (ATP) on the delayed
      rectifier K+ current (IK) were studied in guinea-pig ventricular myocytes using
      the whole-cell voltage-clamp technique. ATP increased IK concentration
      dependently with a concentration eliciting a half-maximal response of 1.86 microM
      and a maximal increase of about 1.8-fold. The enhancement of IK developed slowly,
      the effect reaching a maximum in about 1.6 min after application of ATP. The rank
      order of agonist potency in enhancing IK was 2-methylthio-ATP>/= ATP>>alpha,beta
      methylene-ATP. The ATP response was attenuated in guanosine 5'-O-(2
      thiodiphosphate) (GDPbetaS)- loaded cells, but was not affected by pertussis
      toxin (PTX)-pre-treatment, indicating that a PTX-insensitive G protein is
      involved in the response. These features are consistent with operation of P2Y
      type purinoceptors. ATP produced a further increase in IK stimulated maximally
      either by isoprenaline (1 microM) through protein kinase A (PKA) or by 12-O
      tetradecanoylphorbol 13-acetate (TPA, 100 nM) through protein kinase C (PKC),
      while 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 10
      microM) did not affect the ATP response, suggesting that PKA and PKC do not
      mediate the response. ATP irreversibly enhanced IK in cells loaded with adenosine
      5'-O-(3-thiotriphosphate) (ATPgammaS, 5 mM) or okadaic acid (10 microM), a
      phosphatase inhibitor, suggesting that a phosphorylation step is present after
      the receptor stimulation. Genistein, an inhibitor of tyrosine phosphorylation,
      suppressed the ATP response significantly, while daidzein, an inactive analogue
      of genistein, had little effect on it, although both genistein or daidzein alone
      decreased IK. It is hypothesized that tyrosine phosphorylation plays a role in
      the signalling pathway involved in the enhancement of cardiac IK by P2Y
      purinergic stimulation.

PMID- 10087140
TI  - Activation of PKC increases Na+-K+ pump current in ventricular myocytes from
      guinea pig heart.
AB  - We have previously shown activation of alpha1-adrenergic receptors increases Na+
      K+ pump current (Ip) in guinea pig ventricular myocytes, and the increase is
      eliminated by blockers of phosphokinase C (PKC). In this study we examined the
      effect of activators of PKC on Ip. Phorbol 12-myristate 13-acetate (PMA), a PKC
      activator, increased IP at each test potential without shifting its voltage
      dependence. The concentration required for a half-maximal response (K0.5) was 6
      microM at 15 nM cytosolic [Ca2+] ([Ca2+]i) and 13 nM at 314 nM [Ca2+]i. The
      maximal increase at either [Ca2+]i was about 30%. Another activator of PKC, 1, 2
      dioctanoyl-sn-glycerol (diC8), increased Ip similarly. The effect of PMA on IP
      was eliminated by the PKC inhibitor staurosporine, but not by the peptide PKI, an
      inhibitor of protein kinase A (PKA). PMA and alpha1-adrenergic agonist effects
      both were sensitive to [Ca2+]i, blocked by PKC inhibitors, unaffected by PKA
      inhibition, and increased Ip uniformly at all voltages. However, they differed in
      that alpha1-activation caused a maximum increase of 15% vs 30% via PMA, and
      alpha1-effects were less sensitive to [Ca2+]i than PMA effects. These results
      demonstrate that activation of PKC causes an increase in Ip in guinea pig
      ventricular myocytes. Moreover, they suggest that the coupling of alpha1
      adrenergic activation to Ip is entirely through PKC, however alpha1-activation
      may be coupled to a specific population of PKC whereas PMA is a more global
      agonist.

PMID- 10087141
TI  - P-glycoprotein inhibition by glibenclamide and related compounds.
AB  - Glibenclamide is well known to interact with the sulphonylurea receptor (SUR) and
      has been shown more recently to inhibit the cystic fibrosis transmembrane
      conductance regulator protein (CFTR), both proteins that are members of the ABC
      [adenosine 5'-triphosphate (ATP)-binding cassette] transporters. The effect of
      glibenclamide and two synthetic sulphonylcyanoguanidine derivatives (dubbed BM
      208 and BM-223) was examined on P-glycoprotein, the major ABC transporter
      responsible for multidrug resistance (MDR) in cancer cells. To this end, we
      employed different cell lines that do or do not express P-glycoprotein, as
      confirmed by Western blotting: first, a tumour cell line (VBL600) selected from a
      human T-cell line (CEM) derived from an acute leukaemia; second, an epithelial
      cell line derived from a rat colonic adenocarcinoma (CC531(mdr+)) and finally, a
      non tumour epithelial cell line derived from the proximal tubule of the opossum
      kidney (OK). Glibenclamide and the two related derivatives inhibited P
      glycoprotein because firstly, they acutely increased [3H]colchicine accumulation
      in P-glycoprotein-expressing cell lines only; secondly BM-223 reversed the MDR
      phenomenon, quite similarly to verapamil, by enhancing the cytotoxicity of
      colchicine, taxol and vinblastine and thirdly, BM-208 and BM-223 blocked the
      photoaffinity-labelling of P-glycoprotein by [3H]azidopine. Furthermore,
      glibenclamide is itself a substrate for P-glycoprotein, since the cellular
      accumulation of [3H]glibenclamide was low and substantially increased by addition
      of P-glycoprotein substrates (e. g., vinblastine and cyclosporine) only in the P
      glycoprotein-expressing cell lines. We conclude that glibenclamide and two
      sulphonylcyanoguanidine derivatives inhibit P-glycoprotein and that sulphonylurea
      drugs would appear to be general inhibitors of ABC transporters, suggesting an
      interaction with some conserved motif.

PMID- 10087142
TI  - Inactivated state dependence of sodium channel modulation by beta-scorpion toxin.
AB  - We have examined the effects of a beta-scorpion toxin purified from the venom of
      the Venezuelan scorpion Tityus discrepans, TdVIII, on heterologously expressed
      rat skeletal muscle Na+ channels (rSkM1). TdVIII (100 nM) produced a leftward
      shift in the voltage dependence of activation and reduced the peak Na+
      conductance of rSkM1 channels coexpressed with the rat brain beta1 subunit in
      Xenopus laevis oocytes, suggesting that TdVIII is a beta-scorpion toxin. These
      effects did not depend on the presence of the beta1 subunit. Modification of
      rSkM1 activation by TdVIII could be augmented by increasing the rate of
      stimulation (enhanced use-dependence). Shifts in channel activation were also
      enhanced by introducing conditioning pulses to -10 mV, and this enhancement
      increased with conditioning pulse duration. On the other hand, TdVIII did not
      affect the activation of fast-inactivation deficient mutant Na+ channels, I1303Q/
      F1304Q/M1305Q. These results suggest that modulation of rSkM1 Na+ channel gating
      by TdVIII depends on the toxin interacting with the inactivated state of the
      alpha subunit.

PMID- 10087143
TI  - Action potential propagation failures in long-term recordings from embryonic stem
      cell-derived cardiomyocytes in tissue culture.
AB  - Three-dimensional cell aggregates (embryoid bodies, EBs) containing clusters of
      spontaneously beating cardiomyocytes were derived from permanent mouse embryonic
      stem (ES) cells. Extracellular recordings of the population action potentials of
      cardiomyocyte clusters were made using permanently mounted silver wire electrodes
      and microelectrode arrays integrated into the bottom of the culture dish. These
      techniques allowed long-term recordings (for up to several weeks) from individual
      EBs under cell culture conditions. The normal electrical activity consisted of
      regular spiking with a frequency of 0.5-5 Hz. However, most EBs (87%)
      spontaneously developed temporary or persistent complex activity patterns because
      of intermittent block of action potential propagation at narrow pathways
      connecting larger beating areas. Similar propagation blocks could also be
      reversibly induced in regularly spiking EBs by nimodipine (NDP). In addition to a
      slowing of pacemaker activity, NDP (20-200 nM) induced a stepwise decrease of the
      action potential frequency at the recording site. Perforated patch-clamp
      recordings from enzymatically isolated ES-cell-derived cardiomyocytes showed that
      similar activity patterns do not occur at the single-cell level. We suggest that
      this novel approach may provide a useful tool for in vitro studies of chronotropy
      and phenomena of propagation failure similar to AV block.

PMID- 10087144
TI  - Transepithelial capacitance decrease reveals closure of lateral interspace in A6
      epithelia.
AB  - A sine wave method was used to measure transepithelial capacitance (CT) at 4.1
      kHz (CHFT ). Model calculations show that CHFT reflects the equivalent
      capacitance of the series arrangement of apical and basolateral membrane
      capacitance. Cell swelling induced by reducing the basolateral osmolality from
      260 to 140 mosmol/kg H2O (NaCl or sucrose removal) transiently decreased CHFT.
      The decrease in CHFT (DeltaCHFT ) reached its maximum 30 s after the onset of
      cell swelling and a complete recovery of CHFT was attained within 3-4 min.
      DeltaCHFT could be diminished by manoeuvres that reduced the rate or amplitude of
      cell swelling, i.e. lowering the temperature or treatment with low concentrations
      of glutaraldehyde (0.025%). DeltaCHFT increased with the magnitude of the osmotic
      perturbation but saturated at large volume expansions. DeltaCHFT increased with
      culture time. Electron micrographs showed a clear correlation between time course
      of CHFT changes and the closure of the lateral interspace (LIS). A striking
      correlation between the occurrence of CHFT recovery and the ability of the cells
      to develop a regulatory volume decrease (RVD) was found: Gd3+ (0.5 mM) inhibited
      both phenomena. The frequency dependence of CT was obtained from impedance
      spectra recorded over the range of 4 Hz to 22 kHz. These data agree with model
      calculations in which the contribution of the access resistance to the lateral
      membrane was included. All observations are consistent with the idea that
      DeltaCHFT originates from the closure of the LIS during cell swelling. The latter
      phenomenon increases the access resistance to the lateral membrane, which results
      in a marked reduction of the basolateral membrane area detected at high
      frequencies with capacitance measurements.

PMID- 10087145
TI  - IP3-induced Ca2+ release in A7r5 vascular smooth-muscle cells represents a
      partial emptying of the stores and not an all-or-none Ca2+ release of separate
      quanta.
AB  - There is still no agreement on the mechanism of the intracellular action of low
      concentrations of inositol 1,4,5-trisphosphate (IP3). Intracellular Ca2+ stores
      may transiently release some Ca2+ before they become insensitive to IP3.
      Alternatively, stores with a low IP3 threshold may lose all their Ca2+ and the
      others none. We now report that the IP3 threshold was not correlated with the
      extent of Ca2+ release in permeabilized A7r5 smooth-muscle cells. In contrast,
      the maximum rate of release, which was changed either by varying the level of IP3
      receptor (IP3R) activation, or by changing the concentration of IP3R at a
      constant level of IP3R activation, was directly related to the extent of Ca2+
      release. We conclude that IP3-induced Ca2+ release reflects partial emptying of
      the stores and not all-or-none Ca2+ release of separate quanta.

PMID- 10087146
TI  - A novel method of extraction of TnC from skeletal muscle myofibrils.
AB  - Incubation of mechanically skinned barnacle myofibrillar bundles in 10 mM
      orthovanadate (pH 6.6) results in the loss of Ca2+-dependent force generation,
      which reduces to 0.98+/-0.006% (mean +/-SEM, n=25) of control levels. Analysis of
      myofibrillar bundles by gel electrophoresis showed that tension loss is primarily
      due to the extraction of troponin C (TnC) (65.4+/-5.04% mean +/-SEM, n=5). This
      is a novel finding, since treating cardiac fibres with orthovanadate results in
      the removal of both TnC and troponin I (TnI) (28). Ca2+ dependence was restored
      to the myofibrillar bundles following reconstitution with either native isoform
      of barnacle TnC (BTnC1: 78. 72+/-12.8%, n=9, BTnC2: 82.73+/-20.3%, n=3). The
      reversible loss of Ca2+-dependent tension generation following the removal and
      replacement of TnC indicates that the regulation of contraction in the barnacle
      is controlled by thin-filament regulatory proteins.

PMID- 10087147
TI  - Adrenoceptor-mediated regulation of myofibrillar Ca2+ sensitivity through the GTP
      binding protein-related mechanisms: tension recording in beta-escin-skinned
      single rat cardiac cells with preserved receptor functions.
AB  - To investigate the mechanisms of receptor-mediated regulation of heart muscle
      contraction, we developed a tension-recording system using beta-escin-skinned
      single cardiac cells of rats and studied the effects of agonists on myofibrillar
      Ca2+ sensitivity and Ca2+ release from the sarcoplasmic reticulum (SR). In
      pCa/tension relations, 1 microM isoproterenol plus 100 microM guanosine 5'
      triphosphate (GTP) decreased the myofibrillar Ca2+ sensitivity (pCa50, the [Ca2+]
      required for half-maximal tension, as an indicator of the sensitivity; from 6.07
      to 5.92); this effect was blocked by 1 microM metoprolol or 1 mM guanosine 5'-O
      (2-thiodiphosphate) (GDPbetaS). Phenylephrine (10 microM) plus 100 microM GTP
      increased the Ca2+ sensitivity (pCa50; from 6.12 to 6. 28), and this effect was
      blocked by 1 microM phentolamine or 1 mM GDPbetaS. After Ca2+ loading into the
      SR, 10 microM phenylephrine plus 100 microM GTP in a low-ethylene- glycol
      bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, 0. 1 mM) relaxing
      solution induced oscillatory contractions that were attenuated by either 1 microM
      phentolamine or pre-treatment with 10 microM inositol 1,4,5-trisphosphate. Our
      results demonstrate that beta1-adrenergic stimulation decreases myofibrillar Ca2+
      sensitivity and that alpha1-adrenergic stimulation both increases the Ca2+
      sensitivity and activates Ca2+ release from the agonist-sensitive SR through GTP
      binding protein-related mechanisms.

PMID- 10087148
TI  - A T-type calcium channel from mouse brain.
AB  - A member of the low-voltage-activated calcium channel family was identified in
      mouse brain by taking advantage of amino acid sequences that have been
      evolutionary conserved. The identified sequence is similar to that of the
      recently cloned rat alpha1G T-type calcium channel, but there are differences in
      two insertions in the intracellular connecting loops. Northern blot analysis
      indicates that its expression is strong in the brain. In situ hybridization
      revealed that, in mouse brain, the alpha1G mRNA is found in the cerebellum,
      hippocampus, thalamus and olfactory bulb. In contrast to L-type calcium channel
      currents, IBa and ICa through the alpha1G channel expressed in HEK293 cells did
      not differ in terms of current density, voltage dependence of current activation,
      inactivation and deactivation, and speed of recovery from voltage-dependent
      inactivation. The kinetics of ICa inactivation were significantly slower than
      those of IBa. The expressed alpha1G channel has a relatively high sensitivity to
      mibefradil, but is only slightly affected by Ni2+.

PMID- 10087149
TI  - The Ca2+-sensing receptor in the rabbit cortical thick ascending limb (CTAL) is
      functionally not coupled to phospholipase C.
AB  - The recently cloned rabbit kidney Ca2+-sensing receptor (RabCaR) was functionally
      characterized in microperfused rabbit cortical thick ascending limb (CTAL)
      segments. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that
      this nephron segment contains mRNAs coding for the RabCaR. Elevation of the
      extracellular Ca2+ concentration ([Ca2+]e) from 1 to 5 mmol l-1 induced an
      increase in the fluorescence emission ratio (R), thus reflecting an increase in
      intracellular Ca2+ activity ([Ca2+]i). This increase was inhibited by verapamil,
      nifedipine and SKF 96365, and potentiated by a previous application of Bay K
      8644. Neither verapamil nor Bay K 8644 modified the resting [Ca2+]i. This
      suggests that the basolateral Ca2+ influx induced by a high [Ca2+]e occurs via
      verapamil- and dihydropyridine-sensitive Ca2+ channels, which are not open under
      resting conditions. In contrast to that evoked by antidiuretic hormone (ADH), the
      [Ca2+]i increase induced by a high [Ca2+]e did not result from an accumulation of
      inositol phosphates. Neomycin, Gd3+, Mg2+, commonly used agonists of the Ca2+
      sensing receptor, did not increase the [Ca2+]i. In the presence of verapamil, ADH
      still produced a transient [Ca2+]i increase that was not observed in the presence
      of an increased [Ca2+]e. These results suggest that the RabCaR in rabbit CTAL
      cells is not functionally coupled to phospholipase C. In conclusion, the high
      [Ca2+]e-induced [Ca2+]i increase involves verapamil- and dihydropyridine
      sensitive Ca2+ channels and is independent of phosphoinositide metabolism.
      Whether these channels are activated by the RabCaR remains to be elucidated.

PMID- 10087150
TI  - Chloride conductance in HT29 cells: investigations with apical membrane vesicles
      and RT-PCR.
AB  - Vesicles enriched in a marker enzyme for apical membranes were isolated from HT29
      cells. These vesicles contain an anion conductance with the selectivity gluconate
      approximately sulphate<F-<Cl-<Br-<NO3-<I-<SCN-. K+ diffusion potential-driven
      36Cl- uptake was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB)>4,
      4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS)>glibenclamide. The Cl-
      conductance was insensitive to Ca2+ and to extravesicular cyclic adenosine
      monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and inosine 5'
      triphosphate (ITP). Using the reverse transcription polymerase chain reaction (RT
      PCR) technique and sequencing of the amplified products we detected messenger
      ribonucleic acid (mRNA) for the cystic fibrosis transmembrane conductance
      regulator (CFTR), the putative Cl- channel or Cl- channel regulator pICln, and
      the Cl- channels ClC-2, ClC-3, ClC-5 and ClC-6 in HT29 cells. The properties of
      the vesicles' Cl- conductance resemble those of the intermediate conductance
      outwardly rectifying Cl- channel and tentatively exclude contributions of CFTR,
      pICln and ClC-2. Whether ClC-3, ClC-5, ClC-6 are involved in Cl- conductance
      remains to be determined.

PMID- 10087151
TI  - Strophanthidin-induced gain of Ca2+ occurs during diastole and not systole in
      guinea-pig ventricular myocytes.
AB  - We have investigated the effects of inhibiting the Na-K pump with strophanthidin
      on the intracellular Ca2+ concentration ([Ca2+]i), sarcoplasmic reticulum (s.r.)
      Ca2+ content and membrane currents. s. r. Ca2+ content was measured by
      integrating the Na-Ca exchange current resulting from application of 10 mM
      caffeine. The application of strophanthidin increased both diastolic and systolic
      [Ca2+]i. This was accompanied by an increase of s.r. Ca2+ content from a resting
      value of 17.9+/-1.5 micromol/l to 36.9+/-3.3 micromol/l (n=16) after 5 min.
      Systolic fluxes of Ca2+ into and out of the cell before and during strophanthidin
      application were also measured. Ca2+ efflux (measured as the integral of the Na
      Ca exchange tail current) rose steadily in the presence of strophanthidin, while
      Ca2+ influx (the integral of the L-type Ca2+ current) was reduced. In spite of
      this, s.r. Ca2+ content rose substantially. In the presence of Cd2+ (100 microM),
      which inhibits the L-type Ca2+ current, strophanthidin had negligible effects on
      current suggesting that Ca2+ influx via Na-Ca exchange during depolarization does
      not account for the increase of s.r. Ca2+ content. This suggests that changes of
      Ca2+ flux during systole are not responsible for the strophanthidin-induced
      increase of s.r. Ca2+. We conclude that the primary mechanism by which the
      cardiac cell gains Ca2+ when the Na-K pump is inhibited is by a net influx during
      diastole.

PMID- 10087152
TI  - Xenon-induced inhibition of Ca2+-regulated transitions in the cell cycle of human
      endothelial cells.
AB  - Xenon is an anesthetic with very few side-effects, yet its targets at the
      cellular level are still unclear. It interferes with many aspects of
      intracellular Ca2+ homeostasis, but so far no specific event or defined
      regulatory complex of the Ca2+-signaling system has been identified. Specific
      effects of xenon were found by investigating its effects on the cell cycle in
      human endothelial cells: there is a relationship between two cell cycle
      transition points, their regulation by Ca2+, and specific blocks induced by
      xenon. Within the group of substances studied (xenon, isoflurane, desflurane,
      helium, and N2), only xenon blocks the cells almost completely at the G2-M
      transition after a 2-h treatment; those cells that slip through this block are
      then arrested at metaphase. If xenon is removed, cells that have been
      accumulating at the G2-M boundary move into mitosis, and cells blocked at
      metaphase complete their mitosis normally. No such specific block of the cell
      cycle was found with the other substances studied. An artificial increase of
      intracellular Ca2+ in the submicromolar range, using a very low dose of the Ca2+
      ionophore ionomycin, or a threefold increase of the external Ca2+ concentration
      suffices to lift the xenon-induced metaphase block; the cells enter anaphase
      despite the presence of xenon and complete cell division. Thus, the specific but
      completely reversible inhibition by xenon of the G2-M transition and the block at
      metaphase suggest an interaction with a Ca2+-dependent event involved in the
      control of these processes. The results are consistent with the hypothesis that
      suppression of Ca2+ signals can be considered as a common denominator of the
      effects of xenon on the cell cycle and on the neuronal system during anesthesia.

PMID- 10087153
TI  - ATP acting on P2Y receptors triggers calcium mobilization in primary cultures of
      rat neurohypophysial astrocytes (pituicytes).
AB  - The effect of adenosine triphosphate (ATP) on the intracellular Ca2+
      concentration ([Ca2+]i) of cultured neurohypophysial astrocytes (pituicytes) was
      studied by fluorescence videomicroscopy. ATP evoked a [Ca2+]i increase, which was
      dose dependent in the 2.5-50 microM range (EC50=4.3 microM). The ATP-evoked
      [Ca2+]i rise was not modified during the first minute following the removal of
      external Ca2+. Application of 500 nM thapsigargin inhibited the ATP-dependent
      [Ca2+]i increase. Caffeine (10 mM) and ryanodine (1 microM) did not affect the
      ATP-induced [Ca2+]i rise. The pituicytes responded to various P2 purinoceptor
      agonists with the following order of potency: ATP=ATP[gamma-S]=2-MeSATP>/=ADP,
      where ATP[gamma-S] is adenosine 5'-O-(3-thiotriphosphate) and 2-MeSATP is 2
      methylthio-adenosine-5'-triphosphate. Adenosine, AMP, alpha, beta-methylene
      adenosine-5'-triphosphate (alpha,beta-MeATP), beta, gamma methylene adenosine-5'
      triphosphate (beta,gamma-MeATP) and uridine 5'-triphosphate (UTP) were
      ineffective. The P2 purinoceptor antagonists blocked the ATP-evoked [Ca2+]i
      increase with the following selectivity: RB-2>suramin>PPADS, where RB-2 is
      Reactive Blue 2 and PPADS is pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic
      acid. The ATP-evoked [Ca2+]i increase was substantially blocked by pertussis
      toxin treatment, suggesting that it might be mediated by a pertussis-toxin
      sensitive G protein. The phospholipase C (PLC) inhibitor U-73122 (0.5 microM)
      abolished the ATP-evoked [Ca2+]i rise, whereas its inactive stereoisomer U-73343
      (0.5 microM) remained ineffective. Our results indicate that, in rat cultured
      pituicytes, ATP stimulation induces an increase in [Ca2+]i due to PLC-mediated
      release from intracellular stores through activation of a pertussis-toxin
      sensitive, G-protein-linked P2Y receptor.

PMID- 10087154
TI  - The effect of transfection with Botulinum neurotoxin C1 light chain on exocytosis
      measured in cell populations and by single-cell amperometry in PC12 cells.
AB  - We examined the effect on exocytosis in PC12 neuroendocrine cells of transient
      transfection with the specific endoprotease Botulinum neurotoxin C1 light chain
      (BoNT/C1), which cleaves syntaxin and SNAP-25. The effects of toxin expression on
      basal and evoked exocytosis were determined in cell population measurements and
      also in a single-cell transfection-amperometry assay. Co-expression of BoNT/C1
      with human growth hormone (hGH) as a marker of secretory granules in transfected
      cells resulted in a 95% inhibition of hGH release evoked either by the purinergic
      agonist ATP or by depolarization with 55 mM K+. In addition, basal hGH release
      was also inhibited to the same extent. The high level of co-transfection
      efficiency revealed by this extent of inhibition was exploited in a high
      resolution single-cell assay based on cell detection by expression of enhanced
      green fluorescent protein (EGFP) and analysis of evoked dopamine release by
      amperometry using a carbon fibre microelectrode. Cells expressing EGFP alone
      showed population responses and single-cell amperometric responses
      indistinguishable from those of control non-transfected cells. In contrast, co
      expression of BoNT/C1 with EGFP resulted in an almost complete inhibition of
      current transients due to exocytosis evoked by ATP. These results establish and
      validate a single-cell assay of transfection-amperometry for analysing the
      effects of specific proteins on exocytosis.

PMID- 10087155
TI  - Measurement of sugar transport in single living cells.
AB  - A fluorometric method that allows repeatable measurement of sugar transport rates
      and parameters in single living cells is presented. Intracellular sugar
      concentrations were estimated in real time from changes in cell volume that occur
      secondary to permeation of sugars across the plasma membrane. In turn, the cell
      volume changes were estimated from variations of intracellular calcein
      fluorescence measured by confocal microscopy. Using HeLa cells, the assay allowed
      reproducible measurement of the uptake and exit of D-galactose and 3-O-methyl-D
      glucose. The rate of zero-trans uptake (i.e. at an intracellular concentration of
      zero) of galactose at an extracellular concentration of 200 mM was 0.34+/-0.05
      mM/s (n=8). Apparent Vmax and Km for galactose exit were 0.32+/-0.05 mM/s (n=9)
      and 30+/-7.2 mM (n=9), respectively. The apparent affinity of infinite-trans
      (i.e. at a very high intracellular concentration) uptake of 3-O-methyl-D-glucose
      was 3.8+/-0.47 mM (n=8). Galactose uptake was 93+/-8% (n=8) inhibited in the
      presence of 50 microM phloretin, whereas galactose exit was 96+/-6% (n=5) trans
      inhibited by 100 mM 4,6-ethylidine-D-glucose. This technique may help to
      characterize sugar transport in freshly isolated cells, co-cultures and
      heterogeneous cell explants. It may also allow available cell microinjection
      technology to be used to study the regulation of sugar transporters' intrinsic
      activity. In principle, similar approaches might also be applied in functional
      studies of other transporters for which non-metabolized substrates are available.

PMID- 10087156
TI  - Real-time visual detection of Pi released by flagellar dynein ATPase.
AB  - Using a novel fluorescent probe for Pi, a method for the direct visualization of
      Pi release from reactivated flagellar dynein ATPase has been developed. The probe
      undergoes a fluorescence increase when it binds Pi. The technique involves
      simultaneous imaging of demembranated sperm tails by epi-fluorescence and dark
      field microscopy, and the use of the caged ATP technique for axoneme
      reactivation. To limit diffusion and thus maintain the released Pi within the
      observed field of view, the assay is carried out within a minute droplet under
      oil (volume 5-15 pl). The video output of a recursively filtered ICCD camera is
      used to visualize the fluorescence signal, which is subsequently digitized and
      automatically analysed on a PC. A major advantage of this technique is that it
      enables simultaneous analysis of the ATP-utilization rate and the motility of the
      reactivated axonemes.

PMID- 10087157
TI  - Regulatory volume response of erythrocytes exposed to a gradual and slow decrease
      in medium osmolality.
AB  - A sudden decrease in external medium osmolality (90 mosmol/kg) causes an
      immediate swelling of trout erythrocytes, followed by a regulatory volume
      decrease (RVD) due to activation of both a KCl cotransporter and a taurine
      transport pathway. Here, we determined how trout red cells respond when they are
      exposed to a gradual and slow decrease in medium osmolality (80 mosmol/kg at a
      rate of 0.7 mosmol/kg per min). Erythrocytes were unable to regulate their volume
      efficiently when swollen gradually and it increased continuously throughout the
      experimental period (120 min). As long as volume was increased slowly by 15-25%,
      regulatory pathways remained essentially inactivated, erythrocytes losing no
      significant amount of intracellular osmotically active solutes. Above this
      swelling threshold, a response was triggered but the quantity of solutes lost via
      the regulatory pathways was still not sufficient to counterbalance the continuous
      entry of water due to the slow and gradual decrease in medium tonicity.

PMID- 10087158
TI  - Cyclic AMP but not phosphorylation of phospholamban contributes to the slow
      inotropic response to stretch in ferret papillary muscle.
AB  - cAMP has been suggested to mediate the increased intracellular Ca2+ transient and
      contraction seen during the slow response to stretch in cardiac muscle. We
      measured cAMP in ferret papillary muscles stretched from 80-85% to 98% of their
      length at which maximum active tension is produced (Lmax) for 15 min. cAMP was
      significantly (P<0. 05) increased by 53% in muscles at the longer length which
      showed the slow response compared with controls. By contrast, in a population of
      muscles that were stretched but did not show the slow response, cAMP was not
      significantly different from that in muscles at the short length. Although cAMP
      can increase sarcoplasmic reticulum (SR) Ca2+ uptake by phosphorylation of
      phospholamban, we found no significant effect of stretch on phosphorylation of
      phospholamban at either Ser16 or Thr17. Further support for the hypothesis that
      cAMP is a mediator of the slow response was obtained by exposure of some muscles
      to the cell-permeable cAMP antagonist 8-bromo, adenosine 3',5'-cyclic
      monophosphorothioate, Rp isomer (Rp-8-Br-cAMPS, (2.5-10 microM). The slow
      response was reduced by 30% (P<0.05) in the presence of this antagonist. Our
      results not only provide evidence for the mediation of the slow response to
      stretch by cAMP, they also suggest that cAMP may rise in an intracellular
      compartment inaccessible to the SR.

PMID- 10087159
TI  - Cis-acting elements in the 5'-flanking DNA of the malic enzyme gene regulate
      tissue-specific T3-responsiveness in chick embryo fibroblasts.
AB  - Triiodothyronine (T3) stimulates transcription of the malic enzyme gene in chick
      embryo hepatocytes (CEH), but not in chick embryo fibroblasts (CEF), even though
      the two cell types contain similar nuclear T3 binding activities (F. B.
      Hillgartner, W. Chen, and A. G. Goodridge, J. Biol. Chem. 267, 12299-12306,
      1992). Based on Western blot analyses and gel electrophoretic mobility-shift
      assays, differences in mass of thyroid hormone receptor (TR)alpha or binding of
      TRalpha to T3 response element (T3RE) are not responsible for tissue-specific T3
      responsiveness. Using transfection assays, we show that the primary T3RE in RCAS
      TRalpha-CEF, cells that constitutively over-express TRalpha, is located
      downstream of the T3REs that are primarily responsible for T3 responsiveness in
      CEH and is only weakly functional in CEH. T3RE 2, the major T3RE of the malic
      enzyme gene in CEH is active in CEF when the construct does not contain
      additional malic enzyme DNA, but not in constructs containing DNA from -3858 to 
      3541 bp. Responsiveness conferred by T3RE 2 is inhibited in CEF and RCAS-TRalpha
      CEF by three or more cis-acting elements downstream from T3RE 2. One element each
      was localized to fragments from -3622 to -3595 and -3561 to -3541 bp. The
      inhibitory effect of these elements was not observed in CEH and, although they
      cannot explain all of the difference in responsiveness in the two cell types, may
      contribute to the tissue-specific T3 responsiveness of the malic enzyme gene.

PMID- 10087160
TI  - Kinetics of S-adenosylmethionine cellular transport and protein methylation in
      Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense.
AB  - African trypanosomes of the Trypanosoma brucei group are agents of disease in man
      and animals. They present unique biochemical characteristics such as the need for
      preformed purines and have extensive salvage mechanisms for nucleoside recovery.
      In this regard we have shown that trypanosomes have a dedicated transporter for S
      adenosylmethionine (AdoMet), a key metabolite in transmethylation reactions and
      polyamine synthesis. In this study we compared the apparent kinetics of AdoMet
      transport, cytosolic AdoMet pool formation, and utilization of AdoMet in protein
      methylation reactions using two isolates: Trypanosoma brucei brucei, a veterinary
      parasite, and Trypanosoma brucei rhodesiense, a human pathogen that is highly
      refractory and has greatly reduced susceptibility to standard trypanocidal agents
      active against T. b. brucei. The apparent Km values for [methyl-3H]AdoMet
      transport, derived by Hanes-Woolf analysis, for T. b. brucei was 4.2 and 10 mM
      for T. b. rhodesiense, and the Vmax values were 124 and 400 micromol/liter/min,
      respectively. Both strains formed substantial cytosolic pools of AdoMet, 1600
      nmol/10(9) T. b. brucei and 3500 nmol/10(9) T. b. rhodesiense after 10 min
      incubation with 25 mM exogenous AdoMet. Data obtained from washed trichloroacetic
      acid precipitates of cells incubated with [methyl-3H]AdoMet indicated that the
      rate of protein methylation in T. b. brucei was fourfold greater than in T. b.
      rhodesiense. These results demonstrate that the unique rapid uptake and
      utilization of AdoMet by African trypanosomes is an important consideration in
      the design and development of new agents of potential use in chemotherapy.

PMID- 10087161
TI  - Inhibition of p56(lck) tyrosine kinase by isothiazolones.
AB  - Lck encodes a 56-kDa protein-tyrosine kinase, predominantly expressed in T
      lymphocytes, crucial for initiating T cell antigen receptor (TCR) signal
      transduction pathways, culminating in T cell cytokine gene expression and
      effector functions. As a consequence of a high-throughput screen for selective,
      novel inhibitors of p56(lck), an isothiazolone compound was identified, methyl-3
      (N-isothiazolone)-2-thiophenecarboxylate(A-125800), which inhibits p56(lck)
      kinase activity with IC50 = 1-7 microM. Under similar assay conditions, the
      isothiazolone compound was equipotent in blocking the ZAP-70 tyrosine kinase
      activity but was 50 to 100 times less potent against the catalytic activities of
      p38 MAP kinase and c-Jun N-terminal kinase 2alpha. A-125800 blocked activation
      dependent TCR tyrosine phosphorylation and intracellular calcium mobilization in
      Jurkat T cells (IC50 = 35 microM) and blocked T cell proliferation in response to
      alloantigen (IC50 = 14 microM) and CD3/CD28-induced IL-2 secretion (IC50 = 2.2
      microM) in primary T cell cultures. Inhibition of p56(lck )by A-125800 was dose-
      and time-dependent and was irreversible. A substitution of methylene for the
      sulfur atom in the isothiazolone ring of the compound completely abrogated the
      ability to inhibit p56(lck) kinase activity and TCR-dependent signal
      transduction. Incubation with thiols such as beta-ME or DTT also blocked the
      ability of the isothiazolone to inhibit p56(lck) kinase activity. LC/MS analysis
      established the covalent modification of p56(lck) at cysteine residues 378, 465,
      and 476. Together these data support an inhibitory mechanism, whereby cysteine 
      SH groups within the p56(lck) catalytic domain react with the isothiazolone ring,
      leading to ring opening and disulfide bond formation with the p56(lck) enzyme.
      Loss of p56(lck) activity due to -SH oxidation has been suggested to play a role
      in the pathology of AIDS. Consequently, a similar mechanism of sulfhydryl
      oxidation leading to p56(lck) inhibition, described in this report, may occur in
      the intact T cell and may underlie certain T cell pathologies.

PMID- 10087162
TI  - Effect of the CCAAT/enhancer binding protein on expression of the gene for
      chicken malic enzyme.
AB  - The gene for malic enzyme is expressed at a high level in chick embryo
      hepatocytes (CEH) treated with triiodothyronine (T3) and at a low level in the
      absence of T3. In chick-embryo fibroblasts (CEF), expression of the malic enzyme
      gene is low and not regulated by T3. Specific nuclear proteins from both CEH and
      CEF bound to a consensus CCAAT/enhancer binding protein (C/EBP) site at -335 to 
      327 bp of the malic enzyme gene. The level of binding was much higher in extracts
      from CEH than in extracts of CEF, and the complexes formed had different
      mobilities. C/EBPalpha was present in the complex that bound to the C/EBP site in
      nuclear extracts from CEH but not in those from CEF. The C/EBP element was
      necessary and sufficient to bestow full T3 responsiveness to 5800 bp of 5'
      flanking DNA of the malic enzyme gene in CEH. C/EBPalpha was not detectable in
      wild-type CEF, and deletion of the C/EBP binding site had no effect on expression
      of transgenes containing 5800 bp of 5'-flanking DNA of the malic enzyme gene. In
      CEF, overexpression of C/EBPalpha stimulated promoter activity of constructs that
      contained the C/EBP site linked to the malic enzyme promoter or a heterologous
      reporter. The results suggest that C/EBPalpha or a closely related isoform is
      involved in the tissue-specific expression of the malic enzyme gene.

PMID- 10087163
TI  - Bacterial expression and characterization of the ligand-binding domain of the
      vitamin D receptor.
AB  - The ligand-binding domain of the rat vitamin D receptor (amino acids 115-423) was
      expressed as an amino-terminal His-tagged protein in a bacterial expression
      system and purified over Ni-nitrilotriacetic acid resin and a Mono S column. The
      purified protein bound its ligand, 1,25-dihydroxyvitamin D3, with high affinity,
      similar to that of the full-length protein. Saturation of the protein with ligand
      quenched 90% of the tryptophan fluorescence, consistent with the purified protein
      being uniformly able to bind ligand. Addition of ligand produced no change in the
      tryptophan fluorescence lifetime, suggesting static quenching as the mechanism of
      fluorescence decrease. The near-UV circular dichroism spectrum showed a large
      increase in signal following the addition of ligand, consistent with a change in
      the environment of aromatic amino acid side chains. The far-UV circular dichroism
      spectrum was consistent with a protein of high alpha-helical content.
      Sedimentation equilibrium experiments demonstrated that the protein formed higher
      order complexes, and the distribution of the protein among these complexes was
      significantly shifted by addition of ligand.

PMID- 10087164
TI  - Thermodynamic properties of an intramolecular DNA four-way junction.
AB  - We have investigated the thermodynamic properties of two homologous DNA four-way
      junctions, J4 and J4M, based on 46-mer linear DNA molecules. J4 and J4M have the
      same base sequence with the only difference that the latter contains an uncharged
      methylene-acetal linkage, -O3'-CH2-O5', instead of the phosphodiester linkage, 
      O3'-PO2-O5'-, between the residues T18 and C19. The comparison of the thermal
      unfolding of the J4 junction and J4M junction serves to investigate the effect of
      the uncharged methylene-acetal linkage on the stability of the junction. Our
      analysis is based on CD, UV absorbance spectroscopy, DSC, and chemical
      footprinting. The aim is to characterize in detail the structure and stability of
      the junctions. As demonstrated before by NMR, in the presence of 5 mM MgCl2 +/-
      50 mM NaCl, both J4 and J4M form a complete four-way junction. This is now
      evidenced by protection from OsO4 cleavage (chemical footprinting). We can assume
      that full base pairing occurs throughout the arms even at the center of the
      junction. CD spectra suggest that the helices within the junctions adopt the
      regular B-DNA conformation. Almost identical melting temperatures and unfolding
      enthalpies are obtained for J4 and J4M both by UV and DSC. Furthermore, the Van't
      Hoff enthalpy (DeltaHVH) derived from UV melting equals the calorimetric enthalpy
      (DeltaHcal), which means that the melting process of the structures proceeds in a
      two-state manner. All results taken together support the conclusion that there
      are no major conformational and energetic differences between J4 and J4M. The
      inclusion of the uncharged methylene-acetal group into the junction has no effect
      on its stability.

PMID- 10087165
TI  - Purification and mode of action of an alkali-resistant endo-1, 4-beta-glucanase
      from Bacillus pumilus.
AB  - Alkaline endo-1,4-beta-d-glucanase was secreted by Bacillus pumilus grown in
      submerged culture on a combination of oat spelt xylan and corn starch as carbon
      sources. The enzyme was purified to homogeneity by Sephacryl S-200 and Q
      Sepharose column chromatography. The protein corresponded to molecular mass and
      pI values of 67 kDa and 3.7, respectively. The enzyme was optimally active at pH
      7.0-8.0 and 60 degrees C and retained 50% of its optimum activity at pH 12. The
      most notable characteristic of the endoglucanase was its high stability up to pH
      12 for 20 h at 30 degrees C. The enzyme hydrolyzed carboxymethylcellulose (CMC)
      and cello-oligosaccharides but was inactive on cellobiose, cellotriose, Avicel,
      xylan, 4-nitrophenyl-beta-d-glucoside, 4-nitrophenyl-beta-d-cellobioside, and 4
      nitrophenyl-beta-d-xyloside. Analysis of reaction mixtures by HPLC revealed that
      the enzyme produced almost exclusively cellotriose when acted on CMC and appeared
      to hydrolyze cello-oligosaccharides by successively releasing cellotriose. The
      use of 4-methylumbelliferyl cello-oligosaccharides and the determination of bond
      cleavage frequency revealed that the enzyme preferentially hydrolyzed the third
      glycosidic bond adjacent to the glycon. The enzyme mediated a decrease in the
      viscosity of CMC associated with a release of only small amounts of reducing
      sugar. The enzyme activity was not inhibited by metal ions, surfactants, and
      chelating agents used as components of laundry detergents.

PMID- 10087166
TI  - Effects of docosahexaenoic and arachidonic acids on the synthesis and
      distribution of aminophospholipids during neuronal differentiation of PC12 cells.
AB  - We have shown previously that docosahexaenoic acid (DHA) promotes and arachidonic
      acid (AA) suppresses neurite outgrowth of PC12 cells induced by nerve growth
      factor (NGF) and that incorporation of [3H]ethanolamine into
      phosphatidylethanolamine (PE) is suppressed in PC12 cells by AA while DHA has no
      effect. In the present study, the effects of these fatty acids on PE synthesis
      via decarboxylation of phosphatidylserine (PS), another pathway of PE synthesis,
      and distribution of aminophospholipids were examined. Incorporation of [3H]serine
      into PS and PE was elevated in the course of NGF-induced differentiation and was
      further stimulated significantly by DHA, but not by AA. [3H]Ethanolamine uptake
      by PC12 cells was significantly suppressed by AA but not by DHA while these fatty
      acids did not affect [3H]serine uptake, indicating that the suppression by AA of
      [3H]ethanolamine incorporation into phosphatidylethanolamine is attributable, at
      least in part, to a reduction in [3H]ethanolamine uptake. The distribution of PE
      in the outer leaflet of plasma membrane decreased during differentiation, which
      is known to be accompanied by an increase in the surface area of plasma membrane.
      Supplementation of PC12 cells with DHA or AA did not affect the distribution of
      aminophospholipids. Thus, DHA and AA affected aminophospholipid synthesis and
      neurite outgrowth differently, but not the transport and distribution of
      aminophospholipids, while the PE concentration in the outer leaflet of the plasma
      membrane decreased in association with morphological changes in PC12 cells
      induced by NGF.

PMID- 10087167
TI  - Extracellular iron reductases: identification of a new class of enzymes by
      siderophore-producing microorganisms.
AB  - This study identifies extracellular iron reductases in culture supernatant fluids
      of the siderophore-producing microorganisms Escherichia coli and Pseudomonas
      aeruginosa. These enzymes were constitutively produced and reduced and released
      iron from a variety of ferric chelators. Dialyzable cofactors, necessary for the
      transfer of electrons in the enzymatic reduction of iron, were identified. The
      reductases were sensitive to treatment with proteinase K and guanidine-HCl, were
      not associated with siderophore activity, and were apparently released from the
      cell as extracellular enzymes. The acquisition of 59Fe2+ by cell suspensions of
      E. coli and P. aeruginosa was saturable, suggesting that the ferrous iron
      generated by these reductases can be bound and transported. Salmonella
      typhimurium mutants feoB, tonB, entB, and entBfeoB, deficient in numerous known
      iron uptake pathways, were found to exhibit substantial extracellular iron
      reducing activities over that of the parent. A hypothesis is proposed in which
      the extracellular iron reductases excreted by siderophore-producing
      microorganisms may be responsible for the mobilization of iron during conditions
      of iron repletion when siderophores are repressed and may also function in
      concert with siderophores during periods of iron starvation.

PMID- 10087168
TI  - Role of glycosylation in the functional expression of an Aspergillus niger
      phytase (phyA) in Pichia pastoris.
AB  - Economical and thermostable phytase enzymes are needed to release phytate
      phosphorus in plant foods for human and animal nutrition and to reduce phosphorus
      pollution of animal waste. Our objectives were to determine if a methylotrophic
      yeast, Pichia pastoris, was able to express a phytase gene (phyA) from
      Aspergillus niger efficiently and if suppression of glycosylation by tunicamycin
      affected its functional expression. The gene (1.4 kb) was inserted into an
      expression vector pPICZalphaA with a signal peptide alpha-factor, under the
      control of AOX1 promoter. The resulting plasmid was transformed into two P.
      pastoris strains: KM71 (methanol utilization slow) and X33 (wild-type). Both host
      strains produced high levels of active phytase (25-65 units/ml of medium) that
      were largely secreted into the medium. The expressed enzyme was cross-reacted
      with the polyclonal antibody raised against the wild-type enzyme and showed two
      pH optima, 2.5 and 5.5, and an optimal temperature at 60 degrees C. Compared with
      the phyA phytase overexpressed by A. niger, this phytase had identical capacity
      in hydrolyzing phytate-phosphorus from soybean meal and slightly better
      thermostability. Deglycosylation of the secreted phytase resulted in reduction in
      the size from 95 to 55 kDa and in thermostability by 34%. Tunicamycin (20
      microg/ml of medium) resulted in significant reductions of both intracellular and
      extracellular phytase activity expression. Because there was no accumulation of
      intracellular phytase protein, the impairment did not seem to occur at the level
      of translocation of phytase. In conclusion, glycosylation was vital to the
      biosynthesis of the phyA phytase in P. pastoris and the thermostability of the
      expressed enzyme.

PMID- 10087169
TI  - Transient peaks in zinc and metallothionein levels during differentiation of
      3T3L1 cells.
AB  - A novel role for zinc mediated by metallothionein (MT) is found in the process of
      differentiation of 3T3L1 mouse fibroblasts to adipocytes. Twenty-four hours after
      the stimulation of differentiation by hormones, the cells enter into a phase of
      synchronous proliferation. In this phase the cellular contents of zinc and
      metallothionein rise rapidly to fivefold and threefold levels, respectively.
      Simultaneously MT is translocated from the cytoplasm to the nucleus. The rise of
      intracellular zinc is essential for the transition from G0/G1- to S-phase of the
      cell cycle. Deprivation of zinc with N,N,N', N'-tetrakis[2
      pyridyl]ethylenediamine, a membrane-permeable zinc chelator, inhibited hormonal
      induced proliferation. After the short phase of proliferation a slower stage of
      actual differentiation to adipocytes begins. The elevated levels of MT and zinc
      decline quickly to start levels, and a rapid redistribution of MT to the
      cytoplasm occurs. We propose that the nuclear translocation of MT mediates the
      transfer of zinc to nuclear factors in the mitogenic process. The redistribution
      of MT to the cytoplasm and the decrease of the zinc content are postulated to be
      required for the start of the actual differentiation.

PMID- 10087170
TI  - Functional characterization of the carnitine transporter defective in primary
      carnitine deficiency.
AB  - Primary carnitine deficiency is an autosomal recessive disorder caused by
      defective carnitine transport which impairs fatty acid oxidation and manifests as
      nonketotic hypoglycemia or skeletal or heart myopathy. Here we report the
      functional characterization of this transporter in human fibroblasts. Carnitine
      enters normal cells by saturable and unsaturable routes, the latter corresponding
      to Na+-independent uptake. Saturable carnitine transport was absent in cells from
      patients with primary carnitine deficiency. In control cells, saturable carnitine
      transport was energized by the electrochemical gradient of Na+. Carnitine uptake
      was not inhibited by amino acid substrates of transport systems A, ASC, and X-AG,
      but was inhibited competitively (in potency order) by butyrobetaine > carnitine >
      palmitoylcarnitine = acetylcarnitine > betaine. Carnitine uptake was also
      noncompetitively inhibited by verapamil and quinidine, inhibitors of the
      multidrug resistance family of membrane transporters, suggesting that the
      carnitine transporter may share a functional motif with this class of
      transporters. A high-affinity carnitine transporter was present in kidney 293
      cells, but not in HepG2 liver cells, whose carnitine transporter had a Km in the
      millimolar range. These result indicate the presence of multiple types of
      carnitine transporters in human cells.

PMID- 10087171
TI  - Affinity labeling of pig lung glutathione S-transferase pi by 4
      (fluorosulfonyl)benzoic acid.
AB  - The compound 4-(fluorosulfonyl)benzoic acid (4-FSB) functions as an affinity
      label of the dimeric pig lung pi class glutathione S-transferase yielding a
      completely inactive enzyme. Protection against inactivation is provided by
      glutathione-based ligands, suggesting that the reaction target is near or part of
      the glutathione binding site. Radioactive 4-FSB is incorporated to the extent of
      1 mol per mole of enzyme subunit. Peptide mapping revealed that 4-FSB reacts with
      two tyrosine residues in the ratio 69% Tyr7 and 31% Tyr106. The ratio is not
      changed by the addition of ligands. The results suggest that only one of the
      tyrosine residues can be labeled in the active site of a given subunit; i.e.,
      reactions with Tyr7 and Tyr106 are mutually exclusive. We propose that the
      difference in labeling of these tyrosine residues is related to their pKa values,
      with Tyr7 exhibiting the lower pKa. The modified enzyme no longer binds to a S
      hexylglutathione-agarose affinity column, even when only one of the active sites
      contains 4-FSB; these results may reflect interaction between the subunits. We
      conclude that Tyr7 and Tyr106 of the pig lung class pi glutathione S-transferase
      are important for function and are located at or close to the substrate binding
      site of the enzyme.

PMID- 10087172
TI  - Permeability and stability properties of membranes formed by lipids extracted
      from Lactobacillus acidophilus grown at different temperatures.
AB  - Lactobacillus acidophilus CRL 640 grown at 25 and 37 degrees C showed a high
      content of cardiolipin, phosphatidylglycerol, and glycolipids. Cultures grown at
      25 degrees C showed a twofold increase in glycolipids in relation to
      phospholipids, a twofold increase in the C16:0 and a fourfold increase in the
      C18:2 fatty acids. In contrast, the C19-cyc and the 10-hydroxy acid (C18:0-10 OH)
      species showed a noticeable decrease. Extracts of total lipids of bacteria grown
      at 25 and 37 degrees C dispersed in water yielded particles having a high
      negative surface potential as measured by electrophoretic mobility. Vesicles
      prepared by extrusion of these dispersions through polycarbonate membranes of 100
      nm pore diameter showed high trapping of carboxyfluorescein (CF), which remained
      unchanged for at least 20 h. The fluorescence anisotropy measured with
      diphenylhexatriene (DPH) and the generalized polarization of Laurdan were
      significantly lower in vesicles prepared with lipids containing the highest
      glycolipid ratio, in comparison to those of bacteria grown at 37 degrees C. No
      phase transition was detected between 5 and 50 degrees C as measured with both
      probes. In accordance with these results, no significant release of the trapped
      CF in this range of temperature was detected. Bile salts and NaCl promoted an
      increase in the fluorescence, which is interpreted as a change in the
      permeability properties of the membrane. This effect was lower with KCl, while
      CaCl2 did not cause any change. The greater permeability change was observed in
      vesicles with a low glycolipid/phospholipid ratio. NaCl did not affect the
      packing of the interface as measured with Laurdan, in contrast to CaCl2. The
      action of Ca+2 may be ascribed to the binding to the negatively charged lipids,
      such as phosphatidyl glycerol and cardiolipin. It is concluded that the higher
      glycolipid/phospholipid ratio and the fatty acids C18:2 and C16:0 enhance the
      lipid membrane stability and decrease the organization in the interfacial and
      hydrocarbon zones. These results are congruent with the behavior of entire
      bacteria subject to osmotic and freeze/thaw stresses.

PMID- 10087173
TI  - Rho-associated kinase: involvement in the cytoskeleton regulation.

PMID- 10087174
TI  - An AMP-dependent (ATP-forming) kinase in the hyperthermophilic archaeon
      Pyrococcus furiosus: characterization and novel physiological role.

PMID- 10087175
TI  - Polycations. 5. Inducement of psi-DNA circular dichroism signals for duplex
      deoxyribonucleotide homopolymers by polycationic strings.
AB  - Atypical circular dichroism intensity enhancements previously associated with Psi
      DNA condensates are reported for poly(dG-dC):poly(dG-dC) and poly(dA-dT):poly(dA
      dT) upon addition to them of a polycationic string salt. Polycationic strings are
      organic species incorporating several cationic sites in a linear array through
      the molecule. The effect observed herein with a small molecule model system holds
      promise for elucidation of the structural details associated with Psi-DNA
      condensate formation.

PMID- 10087176
TI  - A specific inhibitor of the p38 mitogen activated protein kinase affects
      differentially the production of various cytokines by activated human T cells:
      dependence on CD28 signaling and preferential inhibition of IL-10 production.
AB  - Cytokine production upon T cell activation results from the integration of
      multiple signaling pathways from TCR/CD3 and from costimulatory molecules such as
      CD28. Among these pathways, the possible role of p38 mitogen activated protein
      kinase (MAPK) is the least understood. Here, we used a highly specific p38 MAPK
      inhibitor, the SB203580 compound, to examine the role of this enzyme in the
      induction of various cytokines in human T cells stimulated with anti-CD3 and anti
      CD28 mAb together or in combination with PMA. Cytokine induction was monitored by
      ELISA and at the mRNA level. While SB203580 had little effect on IL-2 production
      and proliferation, it significantly reduced the production of several other
      cytokines. The secretion of IL-4, IL-5, IL-13, and TNF-alpha was inhibited by 20
      50% with modes of T cell activation involving the CD28 pathway, whereas their
      mRNA expression was little affected. In contrast, IFN-gamma induction via
      CD28/PMA or CD3/CD28, but not CD3/PMA, was markedly diminished both at the
      protein and at the mRNA levels. Most interestingly, SB203580 also suppressed IL
      10 secretion and mRNA induction via CD28-dependent activation by 75-85% (IC50
      approximately 0.2 microM). Subset analysis suggested that this inhibition did not
      reflect a differential effect on T cell subsets. Therefore, p38 MAPK activity
      appears to contribute to cytokine production, mostly via CD28-dependent
      signaling. Moreover, IL-10 seems to rely more on this activity than other
      cytokines for its induction in T cells.

PMID- 10087177
TI  - Generated single point-mutations can considerably dismantle the lymphocyte
      overstimulation induced by Yersinia pseudotuberculosis superantigen.
AB  - The superantigenic Yersinia pseudotuberculosis-derived mitogen (YPM) may
      contribute to severe complications in Y. pseudotuberculosis infections. Since the
      pathogenic mechanism of a superantigen (SAg) is based on its capability for T
      cell overstimulation, by introducing point mutations into YPM an attempt was made
      to abrogate this effect. Six mutants studied exhibited a variety of T-cell
      proliferating responses. Two had activity reduced by 80-90%, three had activity
      reduced by approximately 50%, and one mutant showed almost no attenuation. The
      SAg-associated in vitro pathogenic functions, cytotoxic activation and the
      production of proinflammatory cytokines, were also diminished, in parallel. Since
      these mutants were confirmed to be defective in TCR Vbeta binding, it was
      possible to compare them with native YPM. Our results suggested that the
      intensity of TCR Vbeta binding is a crucial factor determining the severity of
      pathogenesis and that single amino acid alterations might be useful for producing
      immunotherapeautical agents from native YPM.

PMID- 10087178
TI  - Single cell analysis of antigen-specific T cell responses in HIV-infected
      individuals.
AB  - Antigen-specific and polyclonally induced T cell responses were analyzed in 10
      HIV-infected individuals and in 14 controls by enumerating the numbers of tetanus
      toxoid (TT)-specific and phytohemagglutinin (PHA)-induced IFN-gamma-secreting
      cells (SC) and IL-4-SC using an enzyme-linked immunospot assay. Whereas the
      numbers of IFN-gamma-SC in HIV-infected patients were not different from those of
      the controls in response to an in vitro stimulation with PHA, they were
      significantly decreased in response to an in vitro stimulation with TT, both
      before and after a TT booster. Cell depletion experiments indicated that this
      difference was related to an impairment of CD4(+) T-cell-mediated TT-specific IFN
      gamma secretion. Concerning IL-4, the numbers of both polyclonally induced IL-4
      SC and TT-specific IL-4-SC were significantly lower in HIV-infected patients than
      in the controls. It is concluded that secretion of antigen-specific cytokines of
      both Th1 and Th2 types is depressed in HIV-infected patients.

PMID- 10087179
TI  - Both CD4(+) T cells and CD8(+) T cells are required for iodine accelerated
      thyroiditis in NOD mice.
AB  - The nonobese diabetic (NOD) mouse, a spontaneous animal model for insulin
      dependent diabetes mellitus, displays a tendency in common with human diabetic
      populations to develop autoimmune thyroiditis although incidence and severity of
      thyroid lesions vary widely among different colonies around the world. A congenic
      strain of NOD mice bearing I-Ak on a NOD background (NOD-H2(h4)) has recently
      been derived and displays a much greater tendency to develop thyroiditis and
      autoantibodies to mouse thyroglobulin (MTg) although it is free of diabetes. Both
      thyroid infiltrates and autoantibody formation are accelerated and enhanced in
      NOD-H2(h4) mice by increased iodine intake. The effect of increased iodine intake
      on NOD mice themselves has not been directly investigated although a recent study
      of these animals given high or low doses of iodine showed no follicular
      destruction unless the mice were first rendered goitrous by iodine deprivation.
      We found that dietary iodine increased both the incidence and the severity of
      thyroid lesions in our NOD mice although autoantibodies to MTg were absent. NOD
      background genes appear to be essential for the development of these lesions,
      which were maximal after 4 weeks of iodine administration and showed no
      significant regression when the iodine was stopped. Furthermore, our studies show
      for the first time that both CD4(+) and CD8(+) T cells are necessary for the
      development of this accelerated but essentially spontaneous murine thyroid
      disease.

PMID- 10087180
TI  - Critical role of CD11a (LFA-1) in therapeutic efficacy of systemically
      transferred antitumor effector T cells.
AB  - The systemic adoptive transfer of activated T cells, derived from tumor-draining
      lymph nodes (LNs), mediates the regression of established tumors. In this study,
      the requirement of cell adhesion molecules, CD11a/CD18 (LFA-1), CD54 (ICAM-1),
      CD49d/CD29 (VLA-4), and CD106 (VCAM-1), for T cell infiltration into tumors and
      antitumor function was investigated. Administration of anti-CD11a mAb completely
      abrogated the efficacy of adoptive immunotherapy for both intracranial and
      pulmonary metastatic MCA 205 fibrosarcomas. In contrast, adoptive immunotherapy
      was effective in animals treated with anti-CD49d mAb, anti-CD106 mAb, anti-CD54
      mAb, or in CD54 knockout recipients. Trafficking of transferred cells to the
      intracranial tumor was not affected by any of the mAb. However, the tumor
      specific secretion of IFN-gamma by activated LN T cells was suppressed by anti
      CD11a mAb or anti-CD54 mAb. To account for the different effects of CD11a and
      CD54 blockade in vivo, an additional CD11a/CD18 ligand, CD102 (ICAM-2), was
      demonstrated on tumor-associated macrophages but not on tumor cells. These
      results show that CD11a mediates a critical function in interactions between
      effector T cells, tumor cells, and host accessory cells in situ leading to tumor
      regression.

PMID- 10087181
TI  - Interferon-alpha induction of STATs1, -3 DNA binding and growth arrest is
      independent of Lck and active mitogen-activated kinase in T cells.
AB  - Type I interferons (IFNs) are a family of cytokines that have antiviral and
      antiproliferative effects. Data regarding the processes by which these cytokines
      transduce signals from the cell membrane to the nucleus are becoming increasingly
      complex. The most characterized pathway is via JAK-STAT signaling. Previous
      studies established a potential role for the Src-family kinase Lck in JAK-STAT
      signaling. Therefore, this study was designed to analyze the role of Lck in IFN
      alpha signaling by using the Jurkat, JCam (an Lck-defective cell line derived
      from Jurkat), and JCam/Lck (JCam cells with Lck restored). The results show that
      IFN-alpha can induce MAPK activity, but only in cells containing Lck.
      Furthermore, STATs1 and -3 are effectively phosphorylated and activated to bind
      DNA in the absence of Lck expression in IFN-alpha-treated cells. Finally, the
      results demonstrate that IFN-alpha exerts an antiproliferative effect in all
      three cell lines. These data indicate that Lck and active MAPK do not affect IFN
      alpha-induced growth arrest or induction of STAT1s1 and -3 DNA binding ability.

PMID- 10087182
TI  - Dextran sulfate inhibits IFN-gamma-induced Jak-Stat pathway in human vascular
      endothelial cells.
AB  - Human vascular endothelial cells can be induced by IFN-gamma to express class II
      MHC proteins. Previously, dextran sulfate was shown to selectively inhibit
      expression of class II MHC by preventing transcription of the gene encoding
      CIITA, a transactivator protein required for IFN-gamma-inducible expression of
      class II genes. In this study we characterized the effects of dextran sulfate on
      the intracellular events occurring prior to CIITA activation. Immunoprecipitation
      and Western blot analyses indicated that IFN-gamma-induced phosphorylation of
      Stat1 and Jak2 was blocked by dextran sulfate. In addition, electron micrographs
      showing the large accumulation of dextran sulfate particles in the cytoplasms of
      endothelial cells demonstrated that Stat and Jak proteins may directly interact
      with dextran sulfate. Binding of radiolabeled IFN-gamma to cells indicated that
      dextran sulfate may also modulate IFN-gamma interactions with the cell surface.
      Thus, dextran sulfate is capable of interfering with the IFN-gamma-induced
      expression of class II MHC genes at multiple sites.

PMID- 10087183
TI  - Abundance of NKT cells in the salivary glands but absence thereof in the liver
      and thymus of aly/aly mice with Sjogren syndrome.
AB  - It is known that ALY/Nsc Jcl-aly/aly (aly/aly) mice that congenitally lack lymph
      nodes fall victim to Sjogren syndrome as a function of age. We investigated how
      TCRint cells of extrathymic origin and TCRhigh cells of thymic origin are
      distributed in various organs of these mice. Although the distribution of T-cell
      subsets was not different between control aly/+ and aly/aly mice in youth in any
      of the tested organs, the proportion of TCRint cells in the liver and spleen of
      aly/aly mice increased with aging. Usually, TCRint cells in the liver comprise a
      half-and-half mixture of a NK1. 1(+) subset (i.e., NKT cells) and a NK1.1(-)
      subset. In constrast, almost all expanding TCRint cells in various immune organs
      of aly/aly mice were found to be NK1.1(-). A large proportion of lymphocytes,
      including NK cells and TCRint cells, were also present in the salivary glands of
      aly/aly mice. Interestingly, these TCRint cells in the salivary glands contained
      an NK1.1(+) subset (i.e., NKT cells) that used an invariant chain of
      Valpha14Jalpha281 for TCRalphabeta (>50%). Moreover, gammadeltaT cells that used
      Vgamma 1, 2, 4/Vdelta 1, 4, 6 mRNAs, different from those of gammadeltaT cells in
      the liver and intestine, were abundant. Possibly reflecting the in situ
      generation of these T cells in the salivary glands, the expression of RAG-2 mRNA
      was evident by the RT-RCR method. These results suggest that (i) inflammatory
      lymphocytes that evoke Sjogren syndrome in aly/aly mice are NK cells or TCRint
      cells (both NK1.1(+) and NK1.1(-) subsets) and (ii) TCRint cells in the salivary
      glands might be generated in situ.

PMID- 10087184
TI  - Neuroendocrine-induced synthesis of bone marrow-derived cytokines with
      inflammatory immunomodulating properties.
AB  - Although cytokines and other soluble regulators of immunity are known to be
      involved in hematopoiesis, little is known about the signals that induce the
      synthesis of those mediators locally. Based on recent studies linking the
      neuroendocrine hormone thyrotropin [thyroid-stimulating hormone (TSH)] to immune
      cell function in other tissues, we investigated the capacity of TSH to activate
      cytokine responses from bone marrow cells. These studies reveal that stimulation
      of the TSH receptor on bone marrow cells-using highly purified or recombinant TSH
      or by direct stimulation with anti-TSH receptor antibodies-rapidly induces the
      synthesis of cytokines from bone marrow cells that are classically used in the
      regulation of inflammatory responses. Of 13 cytokines screened for activity by
      ELISA or by RNase protection assays for gene expression, IL-6, IFN-beta,
      TNFalpha, TNFbeta, TGFbeta2, and lymphotoxin-beta responses were reproducibly
      induced by TSH within 2-3 h of stimulation. Intracellularly, TSH stimulation of
      bone marrow cells caused rapid increases in cAMP levels and induced the
      phosphorylation of the Jak2 protein kinase, thereby defining a novel G-protein
      coupled receptor/cytokine synthesis pathway. These findings demonstrate that TSH
      can serve as a primary inductive signal of cytokine production by bone marrow
      cells.

PMID- 10087185
TI  - Decreased proteasome-mediated degradation in T cells from the elderly: A role in
      immune senescence.
AB  - Induction of NFkappaB is a highly regulated process requiring phosphorylation,
      ubiquitination, and proteasome-mediated degradation of the cytosolic inhibitor
      IkappaBalpha. Analyses of the regulation of IkappaBalpha in TNF-alpha-treated T
      lymphocytes from young and elderly donors revealed severely compromised
      degradation of IkappaBalpha in T cells from the elderly. Examination of
      activation-induced phosphorylation and ubiquitination of IkappaBalpha did not
      demonstrate any significant age-related alterations. However, examination of
      proteasome activity in these T cells using fluorogenic peptide assays revealed a
      significant age-related decline in chymotryptic activity. These results suggest
      that a decline in proteasome activity results in a failure to fully degrade
      IkappaBalpha in the elderly. This failure to degrade IkappaBalpha may underlie
      both the observed decrease in NFkappaB induction and the IL-2 receptor expression
      in TNF-treated T cells during aging. Thus, decreased proteasome-mediated
      degradation may be central to immune dysfunction that accompanies aging.

PMID- 10087186
TI  - Soluble, high-affinity dimers of T-cell receptors and class II major
      histocompatibility complexes: biochemical probes for analysis and modulation of
      immune responses.
AB  - T cell receptors (TCR) and major histocompatibility complex (MHC) molecules are
      integral membrane proteins that have central roles in cell-mediated immune
      recognition. Therefore, soluble analogs of these molecules would be useful for
      analyzing and possibly modulating antigen-specific immune responses. However, due
      to the intrinsic low-affinity and inherent solubility problems, it has been
      difficult to produce soluble high-affinity analogs of TCR and class II MHC
      molecules. This report describes a general approach which solves this intrinsic
      low-affinity by constructing soluble divalent analogs using IgG as a molecular
      scaffold. The divalent nature of the complexes increases the avidity of the
      chimeric molecules for cognate ligands. The generality of this approach was
      studied by making soluble divalent analogs of two different classes of proteins,
      a TCR (2C TCR2Ig) and a class II MHC (MCCI-Ek2Ig) molecule. Direct flow cytometry
      assays demonstrate that the divalent 2C TCR2Ig chimera retained the specificity
      of the native 2C TCR, while displaying increased avidity for cognate peptide/MHC
      ligands, resulting in a high-affinity probe capable of detecting interactions
      that heretofore have only been detected using surface plasmon resonance. TCR2IgG
      was also used in immunofluorescence studies to show ER localization of
      intracellular peptide-MHC complexes after peptide feeding. MCCI-Ek2Ig chimeras
      were able to both stain and activate an MCC-specific T cell hybridoma.
      Construction and expression of these two diverse heterodimers demonstrate the
      generality of this approach. Furthermore, the increased avidity of these soluble
      divalent proteins makes these chimeric molecules potentially useful in clinical
      settings for probing and modulating in vivo cellular responses.

PMID- 10087187
TI  - Induction of allergic reactions in guinea pigs with purified house dust mite
      allergens.
AB  - To establish a guinea pig model for house dust mite allergy with purified mite
      allergens, we studied the immune response to two major mite allergens, native Der
      f 1 (nDer f 1) and recombinant Der f 2 (rDer f 2) and crude mite extract in
      Hartley guinea pigs. Animals were immunized with either mite extract, nDer f 1 or
      rDer f 2, four times at 2- to 3-week intervals. Then the guinea pigs were
      examined as to the status of sensitization to the sensitizing antigen.
      Intradermal injection of mite antigens to mite extract-, nDer f 1-, and rDer f 2
      sensitized animals induced both immediate and late-phase cutaneous reactions.
      Allergic airway disease was also provoked by the intranasal instillation of rDer
      f 2 or mite extract. Anti-nDer f 1 and -rDer f 2 IgE as well as anti-mite extract
      IgE were produced in the sensitized guinea pigs and IgE titer for three mite
      antigens were comparable. We concluded that immunization of Hartley guinea pigs
      with nDer f 1 and rDer f 2 achieved sensitization to mite allergens, which was
      comparable to that obtained by the immunization with mite extract. A mite
      allergic model suitable for immunological and pharmacological studies was
      established from rDer f 2-sensitized guinea pigs.

PMID- 10087188
TI  - Facilitated antigen presentation by B cells expressing IgD when responding T
      cells express IgD-receptors.
AB  - In vitro studies have confirmed that cognate interactions between T and B cells
      are required to demonstrate enhanced helper activity using T cells with
      upregulated IgD-receptors (IgD-Rs). We studied the mechanism by which IgD-R+ T
      cells facilitate antibody responses by examining whether T cells also benefit
      from their expression of IgD-R. Experiments were designed to determine whether
      upregulation of IgD-R on T cells facilitates antigen presentation by IgD+ B
      cells. Goat Ig-primed splenic T cells from BALB/c mice were tested for their
      ability to respond to antigen-presenting B cells treated with goat anti-mouse
      (GAM) IgM or GAM IgD. T cell responses to GAM IgM and GAM IgD presented by B
      cells were significantly higher when goat Ig-primed cells were induced to express
      IgD-R by exposure to oligomeric IgD compared with goat Ig-primed control T cells.
      This effect was inhibited when monomeric IgD was added to the cultures. No
      differences in T and IgD-R+ T cell responses were seen using adherent cells as
      APCs. B cells from IgD-/- mice were also tested. Such B cells present antigen to
      IgD-R+ T cells without promoting enhanced responses compared with B cells from
      heterozygous IgD+/- mice. These studies suggest that IgD may play a costimulatory
      role during antigen presentation. We conclude that when T cells are induced to
      express IgD-R, these lectin-like receptors can ligate B cell membrane IgD during
      antigen presentation to facilitate responses of each of the cells engaged in
      cognate interaction, yielding enhanced antigen-specific T cell and B cell
      responses.

PMID- 10087189
TI  - Regulation of CD40L expression by cyclic AMP: contrasting proinflammatory and
      inhibitory actions.
AB  - CD40L expression is well recognized to be of critical importance in initiation of
      the immune response. Because cAMP mediates actions of bronchodilators commonly
      used in asthma, the effects of cAMP in regulating the immune response are of
      major importance. Cyclic AMP was found to either inhibit or markedly increase
      CD40L expression dependent upon the mechanisms of T cell activation. Cyclic AMP
      inhibited CD40L expression induced by TCR activation. In contrast, cAMP enhanced
      CD40L induced by CD2-mediated T cell activation or by calcium-dependent
      mechanisms. While neither CD28 costimulation nor exogenous IL-2 or IL-4 prevented
      cAMP inhibition in TCR activated cells, addition of calcium ionophore to TCR
      activation prevented any inhibitory effects and caused cAMP to increase CD40L
      expression. Actions of cAMP to increase CD40L expression appeared independent of
      PKC and were not a reflection of generalized cellular activation since neither
      CD25 nor CD69 expression was affected. The markedly contrasting actions of cAMP
      to decrease or increase CD40L expression, an important control point in the
      immune response, could be relevant to actions of commonly used medications
      including bronchodilators.

PMID- 10087190
TI  - Contig assembly of bacterial artificial chromosome clones through multiplexed
      fluorescence-labeled fingerprinting.
AB  - A rapid multiplexed fingerprinting method has been developed for bacterial
      artificial chromosome (BAC) contig assembly. Defined subsets of BAC DNA fragments
      that result from digestion by three paired restriction endonucleases are labeled
      with unique fluorescent F-ddATP for each subset. Lists of the labeled fragment
      size are generated by an ABI 377 DNA sequencer and the GeneScan analysis software
      and then processed by an assembly program, FPC (Fingerprinted Contigs), to
      produce contig maps. Data obtained from the multiplexed labeling permit detection
      of smaller overlaps than is observed when data from a single double-digest are
      analyzed. The method has been tested on 98 BACs from chromosome 22 regions where
      large-scale sequencing is under way and also through simulation, using randomly
      generated BAC clones derived from existing DNA sequence data. In each case,
      contig assembly results demonstrated the advantages of multiplexed
      fingerprinting.

PMID- 10087191
TI  - Identification by denaturing high-performance liquid chromatography of numerous
      polymorphisms in a candidate region for multiple sclerosis susceptibility.
AB  - Genetic association analysis of candidate regions where evidence of linkage has
      accumulated is becoming a key issue in the study of complex diseases. A high
      density of markers, at least one per centimorgan, is required to improve the
      chances of observing linkage disequilibrium with disease alleles. A recently
      available single nucleotide polymorphism (SNP) map designed to cover the whole
      genome provides an average density of one marker per 2 cM. In the present study
      we show that the number of markers can be approximately doubled in a selected
      region, thus reaching a density suitable for association studies, by applying a
      completely automated technique for polymorphism detection, denaturing high
      performance liquid chromatography (DHPLC). A systematic search for SNPs was
      performed in the region 5ptel-q13, where weak but convergent evidence for linkage
      with multiple sclerosis has accumulated. Screening for polymorphisms was
      performed on 124 sequence tagged sites (STSs) in the 3'UTR ends of expressed
      sequence tags totaling about 30,000 bp. Thirty SNPs in 28 STSs were found with
      less than 10% overlap with the markers already detected in the same region. The
      data confirm the validity of the approach using DHPLC on expressed gene sequences
      tagged by a set of standard commercially available primers.

PMID- 10087192
TI  - A novel putative transporter maps to the osteosclerosis (oc) mutation and is not
      expressed in the oc mutant mouse.
AB  - The phenotype of mice homozygous for the osteosclerosis (oc) mutation includes
      osteopetrosis, and a variety of studies demonstrate that osteoclasts in these
      mice are present but nonfunctional. We have identified a novel gene that has
      homology to a family of 12-transmembrane domain proteins with transport functions
      and maps to proximal mouse chromosome 19, in a region to which the oc mutation
      has been previously assigned. The putative transporter is abundant in normal
      kidney, but its expression is markedly reduced in kidneys from oc/oc mice when
      tested using Northern and Western analyses. Southern analysis of this gene, which
      we call Roct (reduced in oc transporter), demonstrates that it is intact and
      unrearranged in oc/oc mice. In situ studies show that Roct is expressed in
      developing bone. We propose that the absence of Roct expression results in an
      osteopetrosis phenotype in mice.

PMID- 10087193
TI  - Integrity of human YACs during propagation in recombination-deficient yeast
      strains.
AB  - Several isogenic strains with defects in recombination/repair genes (RAD1, RAD50,
      RAD51, RAD52, RAD54, and RAD55) were examined for their ability to propagate
      accurately a variety of linear and circular yeast artificial chromosomes (YACs)
      containing human DNA inserts. To assess YAC stability, the human DNA inserts were
      internally marked by an ADE2-pBR-URA3 cassette. Following selection for Ura-
      clones on 5-fluoroorotic acid containing medium, the following types of YAC
      deletions were identified: (i) those caused by homologous recombination with a
      telomeric pBR sequence; (ii) internal deletions, presumed to occur by
      recombination between commonly occurring DNA repeats such as Alu and LINE
      sequences; and (iii) deletions leading to loss of part of a YAC arm. rad52 host
      strains, but not other recombination-deficient strains, decreased the rate of all
      types of YAC deletions 25- to 400-fold. We have also developed and tested kar1
      strains with a conditional RAD52 gene that allow transfer of a YAC from any host
      into a recombination-deficient background. These strains provide an efficient
      tool for stabilization of YACs and are useful for allowing additional
      recombinational modification of YACs.

PMID- 10087194
TI  - Genetic and physical analyses of the centromeric and pericentromeric regions of
      human chromosome 5: recombination across 5cen.
AB  - Human centromeres are poorly understood at both the genetic and the physical
      level. In this paper, we have been able to distinguish the alphoid centromeric
      sequences of chromosome 5 from those of chromosome 19. This result was obtained
      by pulsed-field gel electrophoresis after cutting genomic DNA with restriction
      endonucleases NcoI (chromosome 5) and BamHI (chromosome 19). We could thus define
      a highly polymorphic marker, representing length variations of the D5Z1 domain
      located at the q arm boundary of the chromosome 5 centromere. The centromeric
      region of chromosome 5 was then analyzed in full detail. We established an
      approximately 4.6-Mb physical map of the whole region with five rare-cutting
      enzymes by using nonchimeric YACs, two of which were shown to contain the very
      ends of 5cen on both sides. The p-arm side of 5cen was shown to contain an
      alphoid subset (D5Z12) different from those described thus far. Two genes and
      several putative cDNAs could be precisely located close to the centromere.
      Several L1 elements were shown to be present within alpha satellites at the
      boundary between alphoid and nonalphoid sequences on both sides of 5cen. They
      were used to define STSs that could serve as physical anchor points at the
      junction of 5cen with the p and q arms. Some STSs were placed on a radiation
      hybrid map. One was polymorphic and could therefore be used as a second
      centromeric genetic marker at the p arm boundary of 5cen. We could thus estimate
      recombination rates within and around the centromeric region of chromosome 5.
      Recombination is highly reduced within 5cen, with zero recombinants in 58 meioses
      being detected between the two markers located at the two extremities of the
      centromere. In its immediate vicinity, 5cen indeed exerts a direct negative
      effect on meiotic recombination within the proximal chromosomal DNA. This effect
      is, however, less important than expected and is polarized, as different rates
      are observed on both arms if one compares the 0 cM/Mb of the p proximal first 5.5
      Mb and the 0.64 cM/Mb of the q proximal first 5 Mb to the sex-average 1.02 cM/Mb
      found throughout the entire chromosome 5. Rates then become close to the average
      when one goes further within the arms. Finally, most recombinants (21/22),
      irrespective of the arm, are of female origin, thus showing that recombination
      around 5cen is essentially occurring in the female lineage.

PMID- 10087195
TI  - Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors
      expressed predominantly in nervous tissues and mapped proximal to the hereditary
      sensory neuropathy type 1 locus on chromosome 9.
AB  - Query of the expressed sequence tag database with the rat metabotropic GABABR1A
      receptor amino acid sequence using the TFASTA algorithm revealed two partial cDNA
      fragments whose sequence information was then used to isolate by PCR a novel full
      length human cDNA encoding a putative G-protein-coupled receptor (GPCR), termed
      GPR 51. Sequence analysis revealed that it encoded a protein of 941 amino acids,
      similar in size and homology to GABAB receptors followed by metabotropic
      glutamate receptors but not other GPCRs. GPR 51 expressed in COS-1 cells showed
      no specific binding for [3H](+)baclofen and when expressed in Xenopus oocyte and
      Xenopus melanophore functional assays showed no activity to GABA, (-)baclofen,
      and glutamic acid. Northern blot analysis and in situ hybridization revealed that
      GPR 51 transcripts were predominantly expressed in the central nervous system
      with highest abundance in the cortex, thalamus, hippocampus, amygdala,
      cerebellum, and spinal cord. In contrast, GPR 51 receptor transcripts were almost
      not detected in the peripheral tissues. Gene GPR 51 was localized by radiation
      hybrid mapping to chromosome 9, 4.81 cR from the WI-8684 marker, and proximal to
      the hereditary sensory neuropathy type 1 locus.

PMID- 10087196
TI  - Genomic organization and biological characterization of the novel human CC
      chemokine DC-CK-1/PARC/MIP-4/SCYA18.
AB  - The chemokines are a group of chemotactic molecules that appear to regulate the
      directed movement of white blood cells in vitro and in vivo and may therefore
      play important roles in inflammation and immunity. The genes encoding the
      chemokines are clustered in close physical proximity to each other. A large
      cluster of human CC chemokine genes resides on chromosome 17. We have used this
      information in a positional cloning approach to identify novel chemokine genes
      within this cluster. We constructed a YAC contig encompassing the MIP-1alpha
      (HGMW-approved symbol SCYA3) gene region and used exon trapping and sequence
      analysis to isolate novel chemokine genes. Using this approach, a gene encoding a
      chemokine named MIP-4, based on its homology with MIP-1alpha (49.5% identity at
      the nucleotide level and 59.6% at the predicted amino acid level), was found. The
      MIP-4 gene (HGMW-approved symbol SCYA18) consists of three exons spread over 7.1
      kb and is separated from the MIP-1alpha gene by 16 kb. The MIP-4 gene encodes a
      750-bp mRNA that is expressed in lung and macrophages but not in brain or muscle.
      The mRNA encodes an 89-amino-acid protein and includes a predicted signal peptide
      of 21 amino acids. Recombinant or synthetic MIP-4 induced calcium mobilization in
      naive and activated T lymphocyte subpopulations in vitro. Injection of synthetic
      MIP-4 into the peritoneal cavity of mice led to the accumulation of both CD4(+)
      and CD8(+) T lymphocytes, but not monocytes or granulocytes. These observations
      provide new information concerning the arrangement of the CC chemokine gene
      cluster on human chromosome 17 and indicate that the MIP-4 gene product is
      chemotactic in vivo for both CD4(+) and CD8(+) T lymphocytes and may therefore be
      implicated in both humoral and cell-mediated immunity.

PMID- 10087197
TI  - The genomic organization of type I keratin genes in mice.
AB  - We isolated two new keratin cDNAs by screening a cDNA library constructed from
      poly(A)+ RNA of the dorsal and abdominal skin of C57BL/10J mice with a probe of
      human KRT14. Due to its high sequence homology to human keratin 17 cDNA, one full
      length cDNA is most likely to be mouse keratin 17 (Krt1-17) cDNA. The other is
      the putative full-length cDNA of a novel type I keratin gene, designated Krt1
      c29. These two keratin genes were mapped to the distal portion of Chromosome 11,
      where the mouse keratin gene complex-1 (Krt1) is localized. To elucidate the
      genomic organization of Krt1 in mice, we carried out genetic and physical
      analyses of Krt1. A large-scale linkage analysis using intersubspecific
      backcrosses suggested that there are two major clusters in Krt1, one containing
      Krt1-c29, Krt1-10, and Krt1-12 and the other containing Krt1-14, -15, -17, and 
      19. Truncation experiments with two yeast artificial chromosome clones containing
      the two clusters above have revealed that the gene order of Krt1 is centromere
      Krt1-c29-Krt1-10-Krt1-12-Krt1-13-K rt1-15-Krt1-19-Krt1-14-K rt1-17-telomere.
      Finally, we analyzed sequence divergence between the genes belonging to the Krt1
      complex. The results clearly indicated that genes are classified into two major
      groups with respect to phylogenetic relationship. Each group consists of the
      respective gene cluster demonstrated by genetic and physical analyses in this
      study, suggesting that the physical organization of the Krt1 complex reflects the
      evolutionary process of gene duplication of this complex.

PMID- 10087198
TI  - Coding sequence, genomic organization, chromosomal localization, and expression
      pattern of the signalosome component Cops2: the mouse homologue of Drosophila
      alien.
AB  - The Drosophila alien gene is highly homologous to the human thyroid receptor
      interacting protein, TRIP15/COPS2, which is a component of the recently
      identified signalosome protein complex. We identified the mouse homologue of
      Drosophila alien through homology searches of the EST database. We found that the
      mouse cDNA encodes a predicted 443-amino-acid protein, which migrates at
      approximately 50 kDa. The gene for the mouse alien homologue, named Cops2,
      includes 12 coding exons spanning approximately 30 kb of genomic DNA on the
      central portion of mouse chromosome 2. Mouse Cops2 is widely expressed in
      embryonic, fetal, and adult tissues beginning as early as E7.5. Mouse Cops2 cDNA
      hybridizes to two mRNA bands in all tissues at approximately 2.3 and
      approximately 4 kb, with an additional approximately 1.9-kb band in liver.
      Immunostaining of native and epitope tagged proteins localized the mouse Cops2
      protein in both the cytoplasm and the nucleus, with larger amounts in the nucleus
      in some cells.

PMID- 10087199
TI  - Analysis of the promoter from an expanding mouse retrotransposon subfamily.
AB  - The mouse genome contains several subfamilies of the retrotransposon L1. One
      subfamily, TF, contains 4000-5000 full-length members and is expanding due to
      retrotransposition of a large number of active elements. Here we studied the TF
      5' untranslated region (UTR), which contains promoter activity required for
      subfamily expression. Using reporter assays, we show that promoter activity is
      derived from TF-specific monomer sequences and is proportional to the number of
      monomers in the 5' UTR. These data suggest that nearly all full-length TF
      elements in the mouse genome are currently competent for expression. We aligned
      the sequences of 53 monomers to generate a consensus TF monomer and determined
      that most TF elements are truncated near a potential binding site for a
      transcription initiation factor. We also determined that much of the sequence
      variation among TF monomers results from transition mutations at CpG
      dinucleotides, suggesting that genomic TF 5' UTRs are methylated at CpGs.

PMID- 10087200
TI  - Multiple inositol polyphosphate phosphatase: evolution as a distinct group within
      the histidine phosphatase family and chromosomal localization of the human and
      mouse genes to chromosomes 10q23 and 19.
AB  - Multiple inositol polyphosphate phosphatase is the only enzyme known to hydrolyze
      the abundant metabolites inositol pentakisphosphate and inositol
      hexakisphosphate. We have previously demonstrated that the chick homolog of
      multiple inositol polyphosphate phosphatase, designated HiPER1, has a role in
      growth plate chondrocyte differentiation. The relationship of these enzymes to
      intracellular signaling is obscure, and as part of our investigation we have
      examined the murine ((MMU)Minpp1) and human ((HSA)MINPP1) homologs. Northern blot
      analysis demonstrated expression of ((MMU)Minpp1 in a variety of mouse tissues,
      comparable to the expression of other mammalian homologs, but less restricted
      than the expression of HiPER1 in chick. A purified (MMU)Minpp1 fusion protein
      cleaved phosphate from inositol (1,3,4,5)-tetrakisphosphate and para-nitrophenyl
      phosphate. When the presumptive active site histidine was altered to alanine by
      site-directed mutagenesis, enzyme activity was abolished, confirming the
      classification of (MMU)Minpp1 as a histidine phosphatase. The amino acid
      sequences of the murine and human MINPP proteins share >80% identity with the rat
      enzyme and >56% identity with HiPER1, with conservation of the C-terminal
      consensus sequence that retains proteins in the endoplasmic reticulum. The
      intron/exon structure of the mammalian (MMU)Minpp1 and (HSA)MINPP1 genes is also
      conserved compared to the chick HiPER1 gene. Sequence analysis of plant and fruit
      fly MINPP homologs supports the hypothesis that the MINPP enzymes constitute a
      distinct evolutionary group within the histidine phosphatase family. We have
      mapped (HSA)MINPP1 to human chromosome 10q23 by fluorescence in situ
      hybridization, YAC screening, and radiation hybrid mapping. This assignment
      places (HSA)MINPP1 in a region of chromosome 10 that is frequently mutated in
      human cancers and places (HSA)MINPP1 proximal to the tumor suppressor PTEN, which
      maps to 10q23.3. Using a radiation hybrid panel, we localized (MMU)Minpp1 to a
      region of mouse chromosome 19 that includes the murine homolog of Pten. The
      evolutionary conservation of this novel enzyme within the inositol polyphosphate
      pathway suggests a significant role for multiple inositol polyphosphate
      phosphatase throughout higher eukaryotes.

PMID- 10087201
TI  - pPAC-ResQ: A yeast-bacterial shuttle vector for capturing inserts from P1 and PAC
      clones by recombinogenic targeted cloning.
AB  - We have developed a method to capture inserts from P1 and P1 artificial
      chromosome (PAC) clones into a yeast-bacteria shuttle vector by using
      recombinogenic targeting. We have engineered a vector, pPAC-ResQ, a derivative of
      pClasper, which was previously used to capture inserts from yeast artificial
      chromosome clones. pPAC-ResQ contains DNA fragments flanking the inserts in P1
      and PAC vectors as recombinogenic ends. When linearized pPAC-ResQ vector and P1
      or PAC DNA are cotransformed into yeast, recombination between the two leads to
      the transfer of inserts into pPAC-ResQ. pPAC-ResQ clones thus obtained can be
      further modified in yeast for functional analysis and shuttled to Escherichia
      coli to produce large quantities of cloned DNA. This approach provides a rapid
      method to modify P1/PAC clones for functional analysis.

PMID- 10087202
TI  - Cloning and characterization of UXT, a novel gene in human Xp11, which is widely
      and abundantly expressed in tumor tissue.
AB  - Several different disease loci with unknown genetic background map to human Xp11.
      In a systematic search for novel genes, we identified a novel transcript, UXT
      (HGMW-approved symbol), close to the ELK1 locus in Xp11.23-p11.22. The gene is
      composed of seven exons and encodes a protein of 157 amino acids, which is highly
      conserved in mouse. We showed that UXT is ubiquitously expressed and subject to X
      inactivation. No homology to any known genes was found. Database surveys indicate
      an abundant expression in tumor tissues.

PMID- 10087203
TI  - Radiation hybrid mapping of chromosomal region 2p15-p16: integration of expressed
      and polymorphic sequences maps at the Carney complex (CNC) and Doyne honeycomb
      retinal dystrophy (DHRD) loci.
AB  - Chromosomal region 2p15-p16, which corresponds to the genetic interval flanked by
      polymorphic markers D2S119 and D2S378 and covers a genetic distance of
      approximately 16 cM, is underrepresented in the existing maps of chromosome 2.
      This is primarily due to two large gaps of unknown physical distance within the
      known yeast and bacterial artificial chromosome (YAC and BAC, respectively) maps.
      In constructing a YAC/BAC contig covering 2p15-p16, a total of 55 sequence-tagged
      sites (25 of which are polymorphic), including new sequences derived from
      chromosomal walking, and 38 expressed sequence tags were screened by a
      commercially available RH panel (Stanford G3). A total of 45 of these sequences
      were placed; 32 of them were assigned at unique sites. The high-resolution TNG3
      RH panel was then used to define further the chromosomal order of markers
      contained in the region flanked by D2S391 and D2S2153. This region harbors the
      genes for two autosomal dominant disorders, Carney complex (CNC), a multiple
      neoplasia syndrome, and Doyne honeycomb retinal dystrophy (DHRD), a disease
      leading to blindness at a young age. This is the first attempt to order cloned
      sequences in chromosomal region 2p15-p16, an area apparently resistant to YAC
      cloning. Construction of the 2p15-p16 RH map is critical for identifying the
      genes responsible for CNC and DHRD, as well as for the molecular elucidation of a
      chromosomal region that is frequently rearranged in tumors.

PMID- 10087204
TI  - Mapping of the KHSRP gene to a region of conserved synteny on human chromosome
      19p13.3 and mouse chromosome 17.
AB  - The K homology-type splicing regulatory protein, KSRP, activates splicing through
      intronic splicing enhancer sequences. It is highly expressed in neural cells and
      is required for the neural-specific splicing of the c-src N1 exon. In this study,
      we mapped the gene (gene symbols KHSRP and Khsrp) to human chromosome 19 by using
      radiation hybrid panels and to mouse chromosome 17 by studying an interspecific
      backcross panel. Human KHSRP is a positional candidate gene for familial febrile
      convulsion and Cayman type cerebellar ataxia. Comparative analysis of the human
      and mouse genomes indicates that the KHSRP gene is located in regions of
      conserved synteny between the two species.

PMID- 10087205
TI  - Assembly of a BAC contig of the complementation group B cell senescence gene
      candidate region at 4q33-q34.1 and identification of expressed sequences.

PMID- 10087206
TI  - Human caveolin-1 and caveolin-2 are closely linked genes colocalized with WI-5336
      in a region of 7q31 frequently deleted in tumors.

PMID- 10087207
TI  - The mouse Fubp gene maps near the distal end of chromosome 3.

PMID- 10087208
TI  - Genetic mapping of mouse heat shock protein genes Hsc4a to chromosome 11 and
      Hsc74 to chromosome 18 and two Hsc74 pseudogenes to chromosomes X and 8.

PMID- 10087209
TI  - Chromosomal mapping of the potassium channel genes Kcnq2 and Kcnq3 in mouse.

PMID- 10087210
TI  - Puromycin-sensitive aminopeptidase gene (Psa) maps to mouse chromosome 11.

PMID- 10087211
TI  - The human 2',5'-oligoadenylate synthetase-like gene (OASL) encoding the
      interferon-induced 56-kDa protein maps to chromosome 12q24.2 in the proximity of
      the 2',5'-OAS locus.

PMID- 10087212
TI  - Dgp1 and Dfp1 are closely related plasmids in the Dictyostelium Ddp2 plasmid
      family.
AB  - Dictyostelium plasmids Dgp1 and Dfp1, two members of the Ddp2 plasmid family, are
      86% identical in nucleotide sequence. These small (4481 and 5015 bp), high copy
      number, nuclear plasmids carry both a gene homologous to the Ddp2 rep gene and a
      long 0.47- to 0. 48-kb inverted repeat region. Their Rep proteins are 82.8%
      identical in amino acid sequence and carry all 10 of the conserved peptide
      sequence motifs found in the Ddp2 family Rep proteins. Unlike other members of
      this family, Dgp1 carries two copies and Dfp1 carries four copies of a 162- to
      166-bp direct repeat element. Both the direct and inverted repeat elements, as
      well as the promoter of the rep gene, are highly conserved (81 to 90% identical)
      between Dgp1 and Dfp1. In contrast, these regions are not highly conserved and
      the Rep proteins are only about 40% identical among the other known members of
      the plasmid family.

PMID- 10087213
TI  - Molecular characterization and interstrain variability of pHPS1, a plasmid
      isolated from the Sydney strain (SS1) of Helicobacter pylori.
AB  - The 5846-bp circular plasmid pHPS1 of Helicobacter pylori Sydney strain, SS1, was
      cloned, sequenced, and structurally characterized. The SS1 strain is widely used
      in animal studies of H. pylori infection. The sequence of pHPS1 revealed three
      open reading frames (ORFs), all of which are transcribed. Two ORFs encode
      putative plasmid replication proteins, RepA and RepB, similar to replicases
      resident on theta plasmids. In contrast, the function of ORF2 remains cryptic due
      to the absence of sequence similarity with any known protein in sequence
      databases. In addition, species specificity of these three coding regions was
      shown using DNA dot blot hybridization in 57 diverse clinical H. pylori isolates
      and 32 Helicobacter and Campylobacter strains. RepA appears to be the predominant
      plasmid replication protein of H. pylori and the deduced amino acid sequence was
      highly conserved (76-96%) in 8 H. pylori isolates, including SS1. RepB was
      detected in 3 H. pylori isolates examined in this study, 2 of which possess only
      the repB gene. Analysis of the protein sequences of these two replicases,
      together with previously characterized H. pylori plasmid replication proteins,
      supports the formation of a distinct class of H. pylori plasmid proteins.
      Moreover, comprehensive analysis of the whole genome sequence of H. pylori strain
      26695, pHPS1, and other H. pylori plasmid sequences that are available revealed
      interesting insights as to the occurrence of plasmid-mediated recombination
      within H. pylori. Common regions between plasmids and chromosome sequences of H.
      pylori were identified in this study which could only have arisen by genetic
      recombination, thus providing the first line of evidence, albeit indirectly, of
      the contribution of H. pylori plasmids in generating an extensive genetic
      heterogeneity characteristic of this important gastroduodenal pathogen.

PMID- 10087214
TI  - Role of the rom protein in copy number control of plasmid pBR322 at different
      growth rates in Escherichia coli K-12.
AB  - The copy number per cell mass of plasmid pBR322 and a rom- derivative was
      measured as a function of generation time. In fast growing cells the copy number
      per cell mass was virtually identical for rom+ and rom- derivatives. However, the
      copy number of pBR322 only increased 3- to 4-fold from a 20- to 80-min generation
      time, whereas the copy number of the rom- derivative increased 7- to 10-fold. The
      copy number stayed constant for the rom+ and rom- plasmids at generation times
      longer than 80-100 min. Thus, the presence of the rom gene decreased the copy
      number of plasmid pBR322 in slowly growing cells at least 2-fold when compared
      with the rom- plasmid. To study the effect of the rom gene in trans we cloned the
      gene into the compatible P15A-derived rom- plasmid pACYC184. In cells carrying
      both pACYC184 rom+ and pBR322 rom- the presence of the rom gene in trans had
      little effect on the copy number of pBR322 rom- at fast growth, but it decreased
      its copy number at slow growth to the same level as found for pBR322, i.e.,
      complemented the pBR322 rom- plasmid. The pACYC184 plasmid and its rom+
      derivatives showed copy numbers similar to those of pBR322 rom- and pBR322
      itself, respectively, at fast and slow growth. We conclude that the rom gene
      product-the Rom protein-is an important element in copy number control of ColE1
      type plasmids especially in slowly growing cells.

PMID- 10087215
TI  - Construction and analysis of a modified Tn4001 conferring chloramphenicol
      resistance in Mycoplasma pneumoniae.
AB  - The Staphylococcus aureus transposon Tn4001 and derivatives thereof have been
      transformed successfully in several mycoplasma species. In order to expand the
      versatility of Tn4001 for other genetic manipulations and for use in mycoplasma
      species resistant to gentamicin (Gm), chloramphenicol acetyltransferase (Cat)
      from S. aureus was evaluated as a selectable marker. The cat gene was cloned in
      both orientations into a modified Tn4001 and transformed into Mycoplasma
      pneumoniae, conferring resistance to Cm and Gm. Replacement of the gene for GmR
      in Tn4001 with cat likewise conferred CmR when transformed into M. pneumoniae.
      The minimum inhibitory concentration to Cm in transformants with cat derivatives
      of Tn4001 was 300-500 microg/ml, and Cat enzyme activity was demonstrated by
      using a fluorescent substrate.

PMID- 10087216
TI  - The putative Orf4 of broad-host-range conjugative plasmid R446 could Be related
      to the H-NS family of bacterial nucleoid-associated proteins.
AB  - The iml determinant of IncM plasmid R446 was described initially as a short
      fragment of DNA causing (when cloned in multicopy plasmids) insensitivity to
      pilus-dependent bacteriophage lysis in bacteria harboring coresident IncM
      plasmids. We have performed a computational analysis of the iml determinant of
      IncM plasmid R446 and found that a potential polypeptide (Orf4) shows similarity
      to the H-NS family of nucleoid-associated modulators of gene expression. The
      predicted protein has a molecular weight of 16.3 kDa and an isoelectric point of
      5.50. Orf4 is adjacent and upstream of Orf5, a potential polypeptide related to
      the Hha/YmoA/RmoA family of proteins which modulate bacterial virulence
      expression (Hha and YmoA) and R100 transfer (RmoA) in response to environmental
      conditions.

PMID- 10087217
TI  - Nucleotide sequence analysis of pRS1, a cryptic plasmid from Oenococcus oeni.
AB  - A new cryptic plasmid, pRS1, from an Oenococcus oeni strain isolated from Spanish
      wines is reported. Nucleotide sequence analysis (2523 bp) revealed the presence
      of three major open reading frames (ORFs) whose nucleotide sequence and encoded
      proteins exhibit high homology with those of pOg32, a previously described
      plasmid of O. oeni. Common features in other plasmids from O. oeni (i.e., pLo13
      and pOg32) have been found in pRS1. They have three major ORFs in the same
      strand; the putative encoded proteins by two of these ORFs exhibit homology with
      the replication (Rep) and the recombination (Pre) proteins, respectively, of the
      pT181 plasmid family and related gram-positive bacteria plasmids; these plasmids
      contain the DNA sequences required for plasmid replication by the rolling circle
      mechanism and for recombination (i.e., double-strand origin, DSO; single-strand
      origin, SSO; recombination-specific sites, RSA and RSB); and finally, all these
      plasmids have a third ORF of unknown function. These features suggest that pRS1
      could constitute together with pLo13 and pOg32 a family of small cryptic plasmids
      of O. oeni.

PMID- 10087218
TI  - Transposition-induced structural instability of Escherichia coli-mycobacteria
      shuttle vectors.
AB  - Escherichia coli-mycobacteria shuttle vectors, derived from pAL5000 (a
      mycobacterial plasmid) and pUC19, were frequently found to undergo structural
      alterations due to transposition of IS1096, a Mycobacterium smegmatis
      transposable element, at a cluster of sites located within a small region of 60
      bp, immediately upstream of a kanamycin resistance gene present in these vectors.
      The structural alterations led to deletion of large regions of the vector which,
      in several cases, were found to extend into the ORF2 (RepB) coding sequences of
      the pAL5000 replication region without affecting its replication capability. This
      suggests that the entire ORF2 coding sequences of the pAL5000 replication region
      may not be essential for replication of pAL5000-derived vectors. The deletion
      derivatives, which contain the minimal sequences required for replication and
      selection in mycobacteria, were found to be structurally stable and therefore
      these could be potentially used as stable vector systems for the transformation
      of mycobacteria.

PMID- 10087219
TI  - Plasmid biology 98: international symposium on plasmid biology 

PMID- 10087220
TI  - U937 cells overexpressing bcl-xl are resistant to human immunodeficiency virus-1
      induced apoptosis and human immunodeficiency virus-1 replication.
AB  - Many viruses, including human immunodeficiency virus type 1 (HIV-1), induce
      apoptosis and are affected by cellular expression of antiapoptotic genes. We
      sought to examine the effect of antiapoptotic gene expression on HIV replication
      by transfecting the promyelomonocytic cell line U937 with the bcl-xl gene to
      obtain clones of U937 cells that overexpressed bcl-xl (designated U937bcl-xl), a
      negative control U937 clone transfected with vector alone (designated U937neo)
      and a clone overexpressing bcl-2 (designated U937bcl-2). After infection with HIV
      1, U937neo cells underwent apoptosis four times as frequently as the U937bcl-xl
      cells. Furthermore, U937bcl-xl cells produced 5-fold less HIV-1 protein than
      U937neo, whereas U937bcl-2 produced at least 2-fold more p24 than the U937neo
      control. Transient coexpression of bcl-2 or bcl-xl decreased HIV production and
      transcription from the HIV LTR. To define the mechanism by which bcl-xl, but not
      bcl-2, inhibits HIV expression, we examined bcl-2 and bcl-xl expression after HIV
      infection and CD4 cross-linking. Although HIV-1 infection or cross-linking CD4
      led to a decrease in expression of bcl-2, it had no effect on bcl-xl expression.
      These results provide a mechanism for the resistance of U937bcl-xl transfectants,
      but not U937bcl-2 transfectants, to HIV-1 replication in monocytic cells in
      vitro. Therapies that up-regulate bcl-xl expression potentially provide a novel
      means to decrease the destructiveness of HIV-1.

PMID- 10087221
TI  - Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral
      effect against vesicular stomatitis virus and encephalomyocarditis virus.
AB  - A cDNA encoding the human guanylate binding protein-1 (hGBP-1) was expressed in
      HeLa cells using a constitutive expression vector. Stably transfected clones
      expressing hGBP-1 exhibited resistance to the cytopathic effect mediated by both
      vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) and
      produced less viral progeny than control cells following infection with these
      viruses. To study the role hGBP-1 plays in the IFN-mediated antiviral effect,
      cells were stably transfected with a construct expressing antisense RNA for hGBP
      1. VSV infection of IFN-alpha-treated antisense RNA-expressing cells produced an
      amount of virus comparable to that produced in the parental cell line, while EMCV
      infection of the IFN-alpha-treated transfected cells and VSV and EMCV infection
      of the IFN-gamma-treated transfected cells produced far more virus than was
      produced in the parental cell line. These results demonstrate that GBP-1 mediates
      an antiviral effect against VSV and EMCV and plays a role in the IFN-mediated
      antiviral response against these viruses.

PMID- 10087222
TI  - Viral burden and disease progression in rhesus monkeys infected with chimeric
      simian-human immunodeficiency viruses.
AB  - To determine the role of viral burden in simian-human immunodeficiency virus
      (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were
      measured after inoculation of rhesus monkeys with four different SHIVs. These
      SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu
      derived from either cell line-passaged or primary patient isolates of human
      immunodeficiency virus type 1; the viral quasispecies SHIV-89.6P derived after in
      vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV
      89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P
      and SHIV-KB9 cause rapid CD4(+) T cell depletion and an immunodeficiency
      syndrome. Relative SHIV provirus levels were highest during primary infection in
      monkeys infected with SHIV-89.6P, the virus that caused the most rapid and
      dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus
      levels were similar in monkeys infected with the pathogenic and nonpathogenic
      chimeric viruses. The virus infections that resulted in the highest peak and
      chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KB9.
      SHIV-89. 6P uniformly caused rapid and profound CD4(+) T cell depletion and
      immunodeficiency. Infection with the SHIV-KB9 resulted in very low CD4(+) T cell
      counts without seroconversion in some monkeys and a substantial but less profound
      CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the
      level of plasma viremia did not differ between SHIV-KB9-infected animals
      exhibiting these contrasting outcomes, suggesting that host factors may play an
      important role in AIDS virus pathogenesis.

PMID- 10087223
TI  - Characterization of human MMTV-like (HML) elements similar to a sequence that was
      highly expressed in a human breast cancer: further definition of the HML-6 group.
AB  - Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high
      levels in a multifocal ductal breast cancer from a 41-year-old woman who also
      developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28)
      selected by high-stringency hybridization with HML-6.2BC1 is reported here. It
      was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total
      DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two
      similar genomic clones and sequences found in GenBank are also reported. Overlaps
      between them gave a rather complete picture of the HML-6.2BC1-like human
      endogenous retroviral elements. Work with somatic cell hybrids and FISH localized
      HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of
      HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6
      sequences enabled the definition of common and unique features of type A, B, and
      D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix
      and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral
      feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but
      gave a phylogenetic tree different from trees made from other ABD genes,
      indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the
      amino terminus of some ABD envelope genes suggested a conserved function.

PMID- 10087224
TI  - Generation of transmissible hepatitis C virions from a molecular clone in
      chimpanzees.
AB  - Multiple alignments of hepatitis C virus (HCV) polyproteins from six different
      genotypes identified a total of 22 nonconsensus mutations in a clone derived from
      the Hutchinson (H77) isolate. These mutations, collectively, may have contributed
      to the failure in generating a "functionally correct" or "infectious" clone in
      earlier attempts. A consensus clone was constructed after systematic repair of
      these mutations, which yielded infectious virions in a chimpanzee after direct
      intrahepatic inoculation of in vitro transcribed RNAs. This RNA-infected
      chimpanzee has developed hepatitis and remained HCV positive for more than 11
      months. To further verify this RNA-derived infectivity, a second naive chimpanzee
      was injected intravenously with serum collected from the first chimpanzee.
      Infectivity analysis of the second chimpanzee demonstrated that the HCV infection
      was successfully transmitted, which validated unequivocally the infectivity of
      our repaired molecular clone. Amino acid sequence comparisons revealed that our
      repaired infectious clone had 4 mismatches with the isogenic clone reported by
      Kolykhalov et al. (1997, Science 277, 570-574) and 8 mismatches with that
      reported by Yanagi et al. (1997, Proc. Natl. Acad. Sci. USA 94, 8738-8743). At
      the RNA level, more mismatches (43 and 67, respectively) were identified; most of
      them were synonymous substitutions. Further comparisons with 16 isolates from
      different genotypes demonstrated that our repaired clone shares greater consensus
      than the reported isogenic clones. This approach of generating infectious HCV RNA
      validates the importance of amino acid sequence consensus in relation to the
      biology of HCV.

PMID- 10087225
TI  - Genetic and antigenic characterization of a serotype P[6]G9 human rotavirus
      strain isolated in the United States.
AB  - During an epidemiologic survey of rotavirus infections established to monitor the
      prevalent G serotypes circulating in the United States, human P[6]G9, subgroup I
      rotavirus strains causing symptomatic infections were identified as the fourth
      most common serotype. In this report we describe the molecular and antigenic
      characterization of one of these P[6]G9 isolates (US1205). Neutralization and
      sequencing studies have demonstrated that both outer capsid proteins, VP7 and
      VP4, of US1205 are closely related to but genetically and antigenically
      distinguishable from those of standard G9 strains (e.g., F45, WI61) and standard
      P2A[6] strains (e. g., ST3, M37). Thus the complete antigenic type of US1205 is
      P2A[6]G9, subgroup I. Sequence analysis of the VP6 and NSP4 genes of US1205
      indicates that strain US1205 possessed VP6 subgroup I and NSP4A genotype
      specificities. Finally, Northern hybridization studies suggest that the P[6]G9
      strains are closely related to members of the DS-1 genogroup except for their
      P[6] VP4 gene, which has been commonly identified in strains of both major human
      genogroups, and their G9 VP7 gene, which may have been derived by reassortment
      with a Wa genogroup strain. Examination of historic collections and prospective
      surveillance of strains will be needed to determine whether this strain has been
      present for some time or if it is emerging to compete with the other common
      serotypes of rotavirus.

PMID- 10087226
TI  - Characterization of a neutralization-escape variant of SHIVKU-1, a virus that
      causes acquired immune deficiency syndrome in pig-tailed macaques.
AB  - A chimeric simian-human immunodeficiency virus (SHIV-4) containing the tat, rev,
      vpu, and env genes of HIV type 1 (HIV-1) in a genetic background of SIVmac239 was
      used to develop an animal model in which a primate lentivirus expressing the HIV
      1 envelope glycoprotein caused acquired immune deficiency syndrome (AIDS) in
      macaques. An SHIV-infected pig-tailed macaque that died from AIDS at 24 weeks
      postinoculation experienced two waves of viremia: one extending from weeks 2-8
      and the second extending from week 18 until death. Virus (SHIVKU-1) isolated
      during the first wave was neutralized by antibodies appearing at the end of the
      first viremic phase, but the virus (SHIVKU-1b) isolated during the second viremic
      phase was not neutralized by these antibodies. Inoculation of SHIVKU-1b into 4
      pig-tailed macaques resulted in severe CD4(+) T cell loss by 2 weeks
      postinoculation, and all 4 macaques died from AIDS at 23-34 weeks
      postinoculation. Because this virus had a neutralization-resistant phenotype, we
      sequenced the env gene and compared these sequences with those of the env gene of
      SHIVKU-1 and parental SHIV-4. With reference to SHIV-4, SHIVKU-1b had 18 and 6
      consensus amino acid substitutions in the gp120 and gp41 regions of Env,
      respectively. These compared with 10 and 3 amino acid substitutions in the gp120
      and gp41 regions of SHIVKU-1. Our data suggested that SHIVKU-1 and SHIVKU-1b
      probably evolved from a common ancestor but that SHIVKU-1b did not evolve from
      SHIVKU-1. A chimeric virus, SHIVKU-1bMC17, constructed with the consensus env
      from the SHIVKU-1b on a background of SHIV-4, confirmed that amino acid
      substitutions in Env were responsible for the neutralization-resistant phenotype.
      These results are consistent with the hypothesis that neutralizing antibodies
      induced by SHIVKU-1 in pig-tailed macaque resulted in the selection of a
      neutralization-resistant virus that was responsible for the second wave of
      viremia.

PMID- 10087227
TI  - The host-cell architectural protein HMG I(Y) modulates binding of herpes simplex
      virus type 1 ICP4 to its cognate promoter.
AB  - The productive infection cycle of herpes simplex virus is controlled in part by
      the action of ICP4, an immediate-early gene product that acts as both an
      activator and repressor of transcription. ICP4 is autoregulatory, and IE-3, the
      gene that encodes it, contains a high-affinity binding site for the protein at
      its cap site. Previously, we had demonstrated that this site could be occupied by
      proteins found in nuclear extracts from uninfected cells. A HeLa cell cDNA
      expression library was screened with a DNA probe containing the IE-3 gene cap
      site, and clones expressing the architectural chromatin proteins HMG I and HMG Y
      were identified by this technique. HMG I is shown to augment binding of ICP4 to
      its cognate site in in vitro assays and to enhance the activity of this protein
      in short-term transient expression assays.

PMID- 10087228
TI  - A GroEL homologue from endosymbiotic bacteria of the whitefly Bemisia tabaci is
      implicated in the circulative transmission of tomato yellow leaf curl virus.
AB  - Evidence for the involvement of a Bemisia tabaci GroEL homologue in the
      transmission of tomato yellow leaf curl geminivirus (TYLCV) is presented. A
      approximately 63-kDa protein was identified in B. tabaci whole-body extracts
      using an antiserum raised against aphid Buchnera GroEL. The GroEL homologue was
      immunolocalized to a coccoid-shaped whitefly endosymbiont. The 30 N-terminal
      amino acids of the whitefly GroEL homologue showed 80% homology with that from
      different aphid species and GroEL from Escherichia coli. Purified GroEL from B.
      tabaci exhibited ultrastructural similarities to that of the endosymbiont from
      aphids and E. coli. In vitro ligand assays showed that tomato yellow leaf curl
      virus (TYLCV) particles displayed a specific affinity for the B. tabaci 63-kDa
      GroEL homologue. Feeding whiteflies anti-Buchnera GroEL antiserum before the
      acquisition of virions reduced TYLCV transmission to tomato test plants by >80%.
      In the haemolymph of these whiteflies, TYLCV DNA was reduced to amounts below the
      threshold of detection by Southern blot hybridization. Active antibodies were
      recovered from the insect haemolymph suggesting that by complexing the GoEL
      homologue, the antibody disturbed interaction with TYLCV, leading to degradation
      of the virus. We propose that GroEL of B. tabaci protects the virus from
      destruction during its passage through the haemolymph.

PMID- 10087229
TI  - Protective effects of type I and type II interferons toward Rous sarcoma virus
      induced tumors in chickens.
AB  - Growth of tumors induced by Rous sarcoma virus (RSV) is controlled by alleles at
      the major histocompatibility complex locus in chickens, indicating that
      immunological host defense mechanisms play a major role. We show here that the
      resistance phenotype of CB regressor chickens can be partially reverted by
      treating the animals with a monoclonal antibody that neutralizes the major
      serotype of chicken type I interferon, ChIFN-alpha. Injection of recombinant
      ChIFN-alpha into susceptible CC progressor chickens resulted in a dose-dependent
      inhibition of RSV-induced tumor development. This treatment was not effective,
      however, in CC chickens challenged with a DNA construct expressing the v-src
      oncogene, suggesting that the beneficial effect of type I interferon in this
      system resulted from its intrinsic antiviral activity and probably not from
      indirect immunmodulatory effects. By contrast, recombinant chicken interferon
      gamma strongly inhibited tumor growth when given to CC chickens that were
      challenged with the v-src oncogene, indicating that the two cytokines target
      different steps of tumor development.

PMID- 10087230
TI  - Strict conservation of the retroviral nucleocapsid protein zinc finger is
      strongly influenced by its role in viral infection processes: characterization of
      HIV-1 particles containing mutant nucleocapsid zinc-coordinating sequences.
AB  - The retroviral nucleocapsid (NC) protein contains highly conserved amino acid
      sequences (-Cys-X2-Cys-X4-His-X4-Cys-) designated retroviral (CCHC) Zn2+ fingers.
      The NC protein of murine leukemia viruses contains one NC Zn2+ finger and mutants
      that were competent in metal binding (CCCC and CCHH) packaged wild-type levels of
      full-length viral RNA but were not infectious. These studies were extended to
      human immunodeficiency virus type 1 (HIV-1), a virus with two NC Zn2+ fingers.
      Viruses with combinations of CCHC, CCCC, and CCHH Zn2+ fingers in each position
      of HIV-1 NC were characterized. Mutant particles contained the normal complement
      of processed viral proteins. Four mutants packaged roughly wild-type levels of
      genomic RNA, whereas the remaining mutants packaged reduced levels. Virions with
      mutated C-terminal position NC fingers were replication competent. One
      interesting mutant, containing a CCCC Zn2+ finger in the N-terminal position of
      NC, packaged wild-type levels of viral RNA and showed approximately 5% wild-type
      levels of infectivity when examined in CD4-expressing HeLa cells containing an
      HIV-1 LTR/beta-galactosidase construct. However, this particular mutant was
      replication defective in H9 cells; all other mutants were replication defective
      over the 8-week course of the assay. Two long terminal repeat viral DNA species
      could be detected in the CCCC mutant but not in any of the other replication
      defective mutants. These studies show that the N-terminal Zn2+ finger position is
      more sensitive to alterations than the C-terminal position with respect to
      replication. Additionally, the retroviral (CCHC) NC Zn2+ finger is required for
      early infection processes. The evolutionary pressure to maintain CCHC NC Zn2+
      fingers depends mainly on its function in infection processes, in addition to its
      function in genome packaging.

PMID- 10087231
TI  - Cellular proteins bind to the poly(U) tract of the 3' untranslated region of
      hepatitis C virus RNA genome.
AB  - UV cross-linking analyses were performed in an attempt to determine cellular
      protein-viral RNA interactions with the 3' untranslated region (3' UTR) of the
      hepatitis C virus RNA genome. Two cellular proteins, with estimated molecular
      masses of 58 kDa (p58) and 35 kDa (p35), respectively, were found to specifically
      bind to the 3' UTR. The p58 protein was determined to be the polypyrimidine tract
      binding protein. In addition to binding to the conserved 98 nucleotides (nt) of
      the 3' UTR, p58 also binds to the poly(U) tract of the 3' UTR. The p35 protein
      was found to interact only with the poly(U) tract of the 3' UTR. These
      conclusions are supported by the following findings: (1) p58, and not p35, binds
      to the 3' end conserved 98 nt, (2) both p58 and p35 bind to a 3' UTR RNA with a
      deletion of the conserved 98 nt, (3) the 98-nt deletion mutant 3' UTR competed
      out both p58 and p35 binding, (4) a poly(U) homopolymer competed out both p58 and
      p35 binding, (5) a 3' UTR RNA with deletion of the poly(U) tract competed out
      only p58 binding but not p35 binding, and (6) an RNA containing the variable
      region of the 3' UTR with a deletion of both poly(U) tract and 98 nt failed to
      compete for binding of either p58 or p35. Interaction of these cellular proteins
      with the HCV 3' UTR is probably involved in regulation of translation and/or
      replication of the HCV RNA genome.

PMID- 10087232
TI  - Effects of double-site mutations of vesicular stomatitis virus glycoprotein G on
      membrane fusion activity.
AB  - Site-directed mutagenesis of specific amino acids within a conserved amino
      terminal region (H2) and a conserved carboxyl-terminal region (H10/A4) of the
      fusion protein G of vesicular stomatitis virus have previously identified these
      two segments as an internal fusion peptide and a region influencing low-pH
      induced conformational change, respectively. Here, we combined a number of the
      substitution mutants in the H2 and H10/A4 regions to produce a series of double
      site mutants and determined the effect of these mutations on membrane fusion
      activity at acid pH and on pH-dependent conformational change. The results show
      that most of the double-site mutants have decreased cell-cell fusion activity and
      that the effects appeared to be additive in terms of inhibition of fusion, except
      for one mutant, which appeared to be a revertant. The double-site mutants also
      had pH optima for fusion that were lower than those observed with wild-type G but
      same as the pH optima for the parent fusion peptide (H2) mutants. The results
      suggest that although the H2 and H10/A4 sites may affect membrane fusion
      independently, a possible interaction between these two sites cannot be ruled
      out.

PMID- 10087233
TI  - Molecular mapping of influenza virus RNA polymerase by site-specific antibodies.
AB  - Influenza virus RNA polymerase with the subunit structure PB1-PB2-PA is involved
      in both transcription and replication of the RNA genome, including the unique cap
      I-dependent RNase activity. To map the important domains for RNA polymerization,
      cap-I-dependent RNase, and cap-I-binding activity, we generated site-specific
      antibodies against overlapping 150-amino-acid peptides that cover each entire
      subunit. Monospecific antibodies against each subunit inhibited RNA synthesis in
      vitro. Those against PB1 and PB2 inhibited the cap-I-dependent RNase activity,
      but those against PB2 alone slightly inhibited the cap-I-binding activity.
      Antibodies against the N-terminal amino acids 1-159 of PB2 that overlap the PB1
      binding site on PB2 and the C-terminal amino acids 501-617 of PA that overlap the
      putative nucleotide-binding site and PB1-binding site on PA inhibited RNA
      polymerizing activity as well as monospecific antibodies. Those against the N
      terminal (amino acids 1-159); the central region (amino acids 305-559) of PB2,
      where a part of the cap-binding domain predicted previously is localized; the N
      terminal (amino acids 1-222) of PB1; and amino acids 301-517 and 601-716 of PA
      inhibited the cap-I-dependent RNase activity. The cap-binding domain on PB2 could
      be mapped in amino acids 402-559, where one of the cap-binding domains mapped
      previously overlapped.

PMID- 10087234
TI  - Structural and functional studies of the measles virus hemagglutinin:
      identification of a novel site required for CD46 interaction.
AB  - The entry of measles virus (MV) into human cells is mediated by the initial
      attachment of the viral hemagglutinin (HA) to the complement regulatory protein
      CD46. Two subdomains, one each within CD46 short consensus repeats (SCRs) 1 and
      2, are responsible for this interaction. However, little is known about the
      regions within MV HA needed for a high-affinity CD46 interaction. To better
      define the HA-CD46 interaction, we took three approaches: chimeric domain
      swapping, peptide scanning, and alanine scanning mutagenesis. Chimeras of MV HA
      and the closely related rinderpest virus (RPV) HA were generated and tested for
      cell surface expression and the ability to hemadsorb CD46+ red blood cells (RBC).
      Exchanges with the N terminus of RPV were tolerated as MV HA could be replaced
      with RPV HA up to amino-acid position 154. However, both larger swaps with RPV
      and a small RPV HA replacement at the C terminus aborted cell-surface expression.
      Peptide scanning with 51 overlapping peptides derived from three MV HA regions
      showed one peptide, corresponding to MV HA amino acids 468-487, blocked
      hemagglutination of African green monkey (AGM) RBCs and inhibited MV infection of
      Chinese hamster ovary cells (CHO) expressing human CD46. Alanine scanning mutants
      mapped sites on the MV HA that were not required for trafficking to the cell
      surface or function in hemagglutination as well as a novel site required for CD46
      interaction, amino acids 473-477.

PMID- 10087235
TI  - The major product of porcine transmissible gastroenteritis coronavirus gene 3b is
      an integral membrane glycoprotein of 31 kDa.
AB  - The open reading frame potentially encoding a polypeptide of 27.7 kDa and located
      as the second of three ORFs (gene 3b) between the S and M genes in the genome of
      the Purdue strain of porcine transmissible gastroenteritis coronavirus (TGEV) was
      cloned and expressed in vitro to examine properties of the protein. Gene 3b has a
      postulated role in pathogenesis, but its truncated form in some laboratory
      passaged strains of TGEV has led to the suggestion that it is not essential for
      virus replication. During synthesis in vitro in the presence of microsomes, the
      27.7-kDa polypeptide became an integral membrane protein, retained its postulated
      hydrophobic N-terminal signal sequence, and underwent glycosylation on apparently
      two asparagine linkage sites to attain a final molecular mass of 31 kDa. A 20-kDa
      N-terminally truncated, nonglycosylated, nonanchored form of the protein was also
      made via an unknown mechanism. The existence of both transmembrane and soluble
      forms of the gene 3 product in the cell is suggested by immunofluorescence
      patterns showing both a punctuated perinuclear and diffuse intracytoplasmic
      distribution. No gene 3b product was found on gradient-purified Purdue TGEV by a
      Western blotting procedure that would have detected as few as 4 molecules/virion,
      indicating the protein probably is not a structural component of the virion.

PMID- 10087236
TI  - Enhancer-like properties of an RNA element that modulates Tombusvirus RNA
      accumulation.
AB  - Prototypical defective interfering (DI) RNAs of the plus-strand RNA virus tomato
      bushy stunt virus contain four noncontiguous segments (regions I-IV) derived from
      the viral genome. Region I corresponds to 5'-noncoding sequence, regions II and
      III are derived from internal positions, and region IV represents a 3'-terminal
      segment. We analyzed the internally located region III in a prototypical DI RNA
      to understand better its role in DI RNA accumulation. Our results indicate that
      (1) region III is not essential for DI RNA accumulation, but molecules that lack
      it accumulate at significantly reduced levels ( approximately 10-fold lower), (2)
      region III is able to function at different positions and in opposite
      orientations, (3) a single copy of region III is favored over multiple copies,
      (4) the stimulatory effect observed on DI RNA accumulation is not due to region
      III-mediated RNA stabilization, (5) DI RNAs lacking region III permit the
      efficient accumulation of head-to-tail dimers and are less effective at
      suppressing helper RNA accumulation, and (6) negative-strand accumulation is also
      significantly depressed for DI RNAs lacking region III. Collectively, these
      results support a role for region III as an enhancer-like element that
      facilitates DI RNA replication. A scanning-type mutagenesis strategy was used to
      define portions of region III important for its stimulatory effect on DI RNA
      accumulation. Interestingly, the results revealed several differences in the
      requirements for activity when region III was in the forward versus the reverse
      orientation. In the context of the viral genome, region III was found to be
      essential for biological activity. This latter finding defines a critical role
      for this element in the reproductive cycle of the virus.

PMID- 10087237
TI  - The myogenic response: established facts and attractive hypotheses.
AB  - The myogenic response of small arteries and arterioles has been shown to
      contribute significantly to autoregulation in different vascular beds. It is
      characterized by a constriction of the vessel after an increase of transmural
      pressure and a dilation of the vessel after a decrease of transmural pressure.
      This review examines the evidence for the mechanisms of the myogenic response,
      with the aim of distinguishing between facts and hypotheses. It appears to be
      established that the myogenic response is stimulated by an alteration of vessel
      wall tension, that it does not require the presence of the endothelium and, for
      pressure increases, that it is accompanied by a membrane depolarization and an
      increase of the intracellular Ca2+ concentration, which depends largely on an
      influx of extracellular calcium via voltage-operated calcium channels. Under in
      vitro conditions, it may further be considered an established fact that the
      myogenic response can be modulated by transmitters, like noradrenaline, and
      factors released from the endothelium upon its activation. In contrast, many
      other aspects of the myogenic response remain hypothetical. Thus, the mechanism
      of the depolarization, its importance for the development of the myogenic
      response, the participation of other pathways for calcium influx, and the role of
      an intracellular calcium release in the myogenic response are still under debate.
      Furthermore, the participation of a variety of intracellular second messenger
      systems in the myogenic response, i.e. inositol trisphosphate, diacylglycerol,
      phospholipase A2, protein kinase C or 20-hydroxyeicosatetraenoic acid, is still
      unclear. Additionally, the roles of the pulsatility of the blood pressure and of
      remote signals from neighbouring vessel segments as well as of different
      metabolites are not clarified. This review suggests that while the primary
      mechanisms of the myogenic response are well understood, the details of the
      signalling pathways are still undefined. The clinical significance of the
      myogenic response remains to be determined.

PMID- 10087238
TI  - Effects of acute prolonged exposure to high-altitude hypoxia on exercise-induced
      breathlessness.
AB  - The direct effects of hypoxia on exercise-induced breathlessness are unclear.
      Increased breathlessness on exercise is known to occur at high altitude, but it
      is not known whether this is related to the hypoxia per se, or to other
      ventilatory parameters. To examine the role of high-altitude hypoxia in exercise
      induced breathlessness, studies were performed in 10 healthy, normal subjects at
      sea level and after acute exposure to an altitude of 4450 m. Although the
      perception of hand weights did not alter between sea level and high altitude, the
      intensity of exercise-induced breathlessness increased significantly at high
      altitude. This was associated with a higher minute ventilation and respiratory
      frequency for any given exercise level, whereas tidal volume was not
      significantly altered from sea level values. The increased intensity of
      breathlessness with exercise did not change significantly over the 5 days at high
      altitude. These results suggest that the increased intensity of exercise-induced
      breathlessness at high altitude is not related to peripheral mechanisms or the
      pattern of ventilation, or to the level of hypoxia per se, but to the level of
      reflexly increased ventilation.

PMID- 10087239
TI  - Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7-36)amide secretion
      by circulating non-esterified fatty acids.
AB  - Two studies were performed to assess the entero-insular axis in simple obesity
      and the possible effect of variations in the level of circulating non-esterified
      fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon
      like peptide-1 [(7-36) amide]. In the first study, we compared the entero
      pancreatic hormone response to oral carbohydrate in obese and lean women. Obese
      subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this
      was not associated with an increased secretion of either glucose-dependent
      insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings
      therefore provide no support for the hypothesis that overactivity of the entero
      insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the
      plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects,
      confirming previous observations. In the second study, in which carbohydrate
      stimulated GLP-1 responses were again evaluated in obese and lean women,
      circulating NEFA levels were modulated using either heparin (to increase serum
      NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in
      complete suppression of NEFA levels and in a markedly higher GLP-1 response than
      the response to carbohydrate alone or to carbohydrate plus heparin. We suggest
      that higher fasting and postprandial NEFA levels in obesity may tonically inhibit
      nutrient-mediated GLP-1 secretion, and that this results in attenuation of the
      GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox
      were similarly suppressed in both lean and obese subjects, the GLP-1 response was
      again significantly lower in obese subjects, suggesting the possibility of an
      intrinsic defect of GLP-1 secretion in obesity. The reduction of GLP-1 levels in
      obesity may be important both in relation to its insulinotropic effect and to its
      postulated role as a satiety factor.

PMID- 10087240
TI  - Serum leptin is associated with the perception of palatability during a
      standardized high-carbohydrate breakfast test.
AB  - Leptin is an adipocyte-derived signalling molecule which plays a key role in the
      regulation of body weight and energy expenditure. Since its involvement in human
      eating behaviour is still poorly understood, we investigated whether the
      perception of palatability of food was related to fasting serum leptin levels.
      Twenty-six non-diabetic subjects, six men and twenty women of widely ranging age
      and body mass index, performed a standardized high-carbohydrate breakfast test.
      Palatability was evaluated with a visual analogue scale, body composition by
      bioelectrical impedance, serum leptin and plasma insulin by radioimmunoassay.
      Palatability was correlated to fasting serum leptin levels independently of body
      mass index, body fat mass and percentage of body fat (P<0.01). No significant
      relation was observed with peaks of insulinaemia, integrated concentrations of
      insulin or insulin resistance indices. A stepwise regression analysis indicated
      that serum leptin gave the strongest predictive association with palatability.
      These results suggest that the leptin system may be involved in the regulation of
      human eating behaviour in relation to the perception of palatability of food.

PMID- 10087241
TI  - Adenosine induces histamine release from human bronchoalveolar lavage mast cells.
AB  - Previous studies have shown that in vitro adenosine enhances histamine release
      from activated human lung mast cells obtained by enzymic dispersion of lung
      parenchyma. However, adenosine alone has no effect on histamine release from
      these cells. Given the evidence for direct activation of mast cells after
      endobronchial challenge with adenosine and previous studies indicating that mast
      cells obtained at bronchoalveolar lavage are a better model for asthma studies
      than those obtained by enzymic dispersion of lung tissue, the histamine-releasing
      effect of adenosine was examined on lavage mast cells. Bronchoalveolar lavage
      fluid was obtained from patients attending hospital for routine bronchoscopy
      (n=54). Lavage cells were challenged with adenosine or adenosine receptor
      agonists (20 min, 37 degrees C) and histamine release determined using an
      automated fluorometric assay. Endogenous adenosine levels were also measured in
      lavage fluid (n=9) via an HPLC method. Adenosine alone caused histamine release
      from lavage mast cells in 37 of 54 patients with a maximal histamine release of
      20.56+/-2.52% (range 5.2-61%). The adenosine receptor agonists (R)-N6-(2
      phenylisopropyl)adenosine, 5'-N-ethylcarboxamidoadenosine and CGS21680 also
      induced histamine release from lavage mast cells. Preincubation of lavage mast
      cells with the adenosine receptor antagonist xanthine amine congener caused
      significant inhibition of the response to adenosine (P=0.007). There was an
      inverse correlation between endogenous adenosine levels in the lavage fluid and
      the maximal response to in vitro adenosine challenge of the lavage cells. The
      findings of the present study indicate a means by which adenosine challenge of
      the airways can induce bronchoconstriction and support a role for adenosine in
      the pathophysiology of asthma. The results also suggest that cells obtained from
      bronchoalveolar lavage fluid may provide the ideal model for the testing of
      novel, adenosine receptor, targeted therapies for asthma.

PMID- 10087242
TI  - Hormone replacement therapy increases isometric muscle strength of adductor
      pollicis in post-menopausal women.
AB  - A randomized open trial of hormone replacement therapy was used to assess changes
      in adductor pollicis muscle strength during 6-12 months of treatment with Prempak
      C 0.625(R) in comparison with an untreated control group. Muscle strength
      (maximal voluntary force; MVF), muscle cross-sectional area and bone mineral
      density were measured. Women entering the trial had oestrogen levels below 150
      pmol.l-1, confirming their post-menopausal hormonal status. In the treated group,
      MVF increased by 12.4+/-1.0% (mean+/-S.E.M.) of initial MVF over the duration of
      treatment, while it declined slightly (2.9+/-0.9%) in the control group. This
      increase in strength could not be explained by an increase in muscle bulk, there
      being no significant increase in cross-sectional area during the study. Those
      subjects who were weakest at enrolment showed the greatest increases in muscle
      strength after treatment. Bone mineral density in total hip, Ward's triangle and
      total spine increased in the treated group, in agreement with previous studies.
      There was no correlation between the individual increases in bone mineral density
      and those in MVF.

PMID- 10087243
TI  - Nitric oxide and penile erection in streptozotocin-diabetic rats.
AB  - The purpose of this investigation was to study the time course, response to
      insulin and characteristics of erectile dysfunction in streptozotocin (STZ)
      diabetic Sprague-Dawley rats, and the function of the NO-generating system in
      these animals. Copulation-induced and reflex erection were quantified in
      conscious Sprague-Dawley rats at different times after injection of STZ. The
      corporal vasodilatation response to nerve stimulation was studied by measuring
      the rise in corporal pressure in pithed rats following electrical stimulation of
      sacral spinal nerve roots. The activity of NO synthase was determined in corporal
      tissue by measuring the generation of [3H]citrulline from [3H]arginine.
      Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment,
      but this could be prevented by a short (2-week) pretreatment with insulin. Reflex
      erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this
      inhibition was also reversible by insulin pretreatment. Following pithing, the
      basal corporal pressure was elevated in diabetic rats. At 4 months after STZ,
      this increase was normalized by a 2-week, but not by a 1-week, pretreatment with
      insulin; however, at 9 months after STZ, insulin pretreatment did not normalize
      corporal pressure. The increase in corporal pressure caused by stimulation of
      sacral nerve roots in pithed rats was enhanced in diabetic animals. This
      enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of
      insulin treatment. The inhibition of the stimulation-induced increase in corporal
      pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9
      months of diabetes, although NO synthase activity was normal in cavernosal tissue
      following 6-8 months of diabetes. In conclusion, STZ-induced diabetes caused
      changes in the erectile system that were initially reversible by a short insulin
      treatment, but which with time (more than 6 months) became irreversible. NO
      synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L
      arginine methyl ester was inhibited in long-term diabetes (9 months).

PMID- 10087244
TI  - An immunoluminometric assay for N-terminal pro-brain natriuretic peptide:
      development of a test for left ventricular dysfunction.
AB  - Measurement of plasma levels of brain natriuretic peptide (BNP) has been used to
      assess left ventricular dysfunction and prognosis. Levels of the N-terminus of
      the precursor of BNP (NT-proBNP) have been reported to be elevated to a greater
      extent than BNP in left ventricular dysfunction. We have devised a non
      radioactive sensitive and specific assay for NT-proBNP based on a competitive
      ligand binding principle. The chemiluminescent label 4-(2
      succinimidyloxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate
      fluorosulphonate was used to label peptides representing domains in the middle
      and C-terminal sections of NT-proBNP. Assay of the C-terminal section of NT
      proBNP (amino acids 65-76) in patients with proven left ventricular dysfunction
      [left ventricular wall motion index median 0.9 (range 0.3-1.4)] revealed elevated
      values [median 639 (386-911) fmol/ml] compared with normal controls [left
      ventricular wall motion index of 2 in all, NT-proBNP median 159 (120-245)
      fmol/ml, P<0.001]. Measurement of the middle section of NT-proBNP (amino acids 37
      49) was not a discriminating test. It is thus possible to derivatize small
      peptides with a methyl acridinium label and preserve immunodetection with
      specific antibodies. Such methodology may allow non-radioactive
      immunoluminometric assays to be devised.

PMID- 10087245
TI  - Soccer players under regular training show oxidative stress but an improved
      plasma antioxidant status.
AB  - Physical activity is known to induce oxidative stress in individuals subjected to
      intense exercise. In this study, we investigated the lipoprotein profile and the
      plasma antioxidant status in a group of soccer players engaged in a regular
      training programme. As was expected for aerobic exercise, high-density
      lipoprotein-cholesterol (HDL-C) and HDL3-C levels were significantly increased in
      the sportsmen (P<0.05). Total plasma antioxidant capacity was 25% higher in
      sportsmen than in controls (P<0.005). Accordingly, plasma hydrosoluble
      antioxidant levels (ascorbic acid and uric acid) were found to be significantly
      elevated in the soccer players (P<0.005). In addition, these subjects showed high
      concentrations of alpha-tocopherol in plasma compared with controls (P<0.005).
      Furthermore, an increase in plasma superoxide dismutase activity was also
      observed in relation to exercise (P<0.01). The elevation in plasma activities of
      antioxidant enzymes and the higher levels of free radical scavengers of low
      molecular mass may compensate the oxidative stress caused by physical activity.
      High levels of high-density lipoprotein in plasma may offer additional protection
      by inhibiting low-density lipoprotein oxidation and thus liposoluble antioxidant
      consumption. Therefore, soccer players under regular training show an improved
      plasma antioxidant status in comparison to sedentary controls.

PMID- 10087246
TI  - Serial changes in sarcoplasmic reticulum gene expression in volume-overloaded
      cardiac hypertrophy in the rat: effect of an angiotensin II receptor antagonist.
AB  - This study was designed to clarify whether gene expression in the cardiac
      sarcoplasmic reticulum [sarcoplasmic reticulum Ca2+-ATPase (SERCA),
      phospholamban, ryanodine receptor and calsequestrin] changes in accordance with
      left ventricular functional alterations in the volume-overloaded heart. Further,
      the effect of the angiotensin II type 1 receptor antagonist, TCV-116, on the
      expression of these genes was also evaluated. Left ventricular fractional
      shortening was significantly increased at 7 days, had returned to control levels
      at 21 days, and had significantly decreased at 35 days after the shunt operation,
      compared with sham-operated rats. The level of SERCA mRNA was significantly
      decreased at both 21 days and 35 days after the shunt operation. The levels of
      ryanodine receptor and phospholamban mRNAs were significantly decreased at 35
      days in shunt-operated rats. The decrease in the SERCA mRNA level preceded the
      development of cardiac dysfunction. The levels of SERCA and ryanodine receptor
      mRNAs were correlated positively with left ventricular fractional shortening
      (r=0.73, P<0.0001 and r=0.61, P<0.01 respectively). Attenuation of the decrease
      in left ventricular fractional shortening occurred on treatment with TCV-116.
      After the treatment with TCV-116, the levels of SERCA and phospholamban mRNAs
      were restored to the respective values in sham-operated rats. Ryanodine receptor
      mRNA levels remained unchanged after treatment with TCV-116. These results
      indicate that the down-regulation of SERCA and ryanodine receptor mRNA levels may
      be related to cardiac dysfunction in the volume-overloaded heart. In addition,
      treatment with an angiotensin II receptor antagonist may restore the altered
      sarcoplasmic reticulum mRNA levels to control levels, and this may result in
      attenuation of the functional impairment in the volume-overloaded heart.

PMID- 10087247
TI  - Pharmacological and molecular biological evidence for ETA endothelin receptor
      subtype mediating mechanical responses in the detrusor smooth muscle of the human
      urinary bladder.
AB  - The aim of this study was to characterize endothelin receptor subtypes of the
      detrusor muscle of the human urinary bladder. The receptor subtypes mediating
      endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been
      characterized using isometric contraction and reverse transcription-polymerase
      chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10(-10) M to
      10(-6) M) exhibited concentration-dependent contractions in human urinary bladder
      with a plateau at concentrations above 3x10(-7) M. Neither IRL1620 nor
      sarafotoxin S6c (both ETB-selective agonists; 10(-10) M to 10(-6) M) elicited
      contractile activity in the human urinary bladder detrusor smooth muscle.
      FR139317 (an ETA-selective antagonist; 10(-7) M to 10(-5) M) produced a marked
      shift to the right of the ET-1 concentration-response curve in human urinary
      bladder detrusor smooth muscle (from the Schild plot TpA2=7.96; slope=0.95). In
      contrast, RES701-1 (an ETB-selective antagonist; 10(-7) M to 10(-5) M) had no
      effect on the ET-1 concentration-response curve. RT-PCR revealed positive
      amplification of ETA receptor mRNA fragment, but not ETB. These results indicate
      that the ET-1-induced contractile effects of urinary bladder detrusor smooth
      muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

PMID- 10087248
TI  - Influence of posture and handgrip on the QT interval in left ventricular
      hypertrophy and in chronic heart failure.
AB  - In certain disease states prolongation of the QT interval has been shown to be
      arrhythmogenic. Whether QTc interval changes with position and thus whether
      certain positions are more arrhythmogenic than others is not known for different
      diseases that predispose to arrhythmias, and was therefore studied. Patients with
      left ventricular hypertrophy and heart failure, and the appropriate matched
      controls, were recruited. Subjects were studied in the lying, sitting, standing
      and squatting positions and had QT intervals determined by computer algorithm 2
      min after each position change. After resting, QT interval was determined while
      the subjects performed maximum handgrip exercise with their dominant hand. QT
      intervals were rate-corrected using Bazett's method. QTc interval is prolonged in
      heart failure patients compared with either left ventricular hypertrophy or
      control subjects in the lying and sitting position, but not in the standing or
      squatting position. The QTc intervals for heart failure and control subjects
      were, respectively, 443+/-7 ms versus 421+/-6 ms when lying (P<0.05), 451+/-10 ms
      versus 419+/-6 ms when sitting (P<0.05), 429+/-10 versus 414+/-7 ms when standing
      (P not significant) and 437+/-10 versus 419+/-8 ms when squatting (P not
      significant). The values for patients with hypertrophy did not differ from
      control values. Maximum handgrip does not affect the QTc interval in heart
      failure, but prolongs it in both the hypertrophy and control groups. Position and
      static exercise are important modifiers of QTc interval and their effect depends
      on the condition of the left ventricle.

PMID- 10087249
TI  - Relationship between mucosal levels of Helicobacter pylori-specific IgA,
      interleukin-8 and gastric inflammation.
AB  - Mucosal IgA is important in local immune defence. Helicobacter pylori induces a
      specific IgA response in antral mucosa, but its immunopathology is unknown.
      Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced
      inflammation. Current information on the relationship between H. pylori-induced
      IgA and mucosal inflammation is limited. To investigate possible associations
      between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of
      IL-8 and gastric inflammation, 52 endoscoped patients were studied. These
      comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these
      patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer
      dyspepsia. Antral biopsies were taken for histology, H. pylori culture and
      measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by
      ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H.
      pylori infection, with a median (interquartile) level of 220 (147, 531) units.
      There was no significant difference in mucosal levels of the IgA antibodies
      between patients infected with cytotoxin-positive or cagA-positive strains of H.
      pylori and those with toxin-negative or cagA-negative strains. The IgA levels in
      those patients with severe neutrophil infiltration were lower than in those with
      mild or moderate infiltration (P<0.05). There was a weak inverse correlation
      between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H.
      pylori infection induced a significant local mucosal IgA response in most
      infected patients. The level of IgA antibodies does not appear to be correlated
      with the toxinogenicity of H. pylori. However, patients with severe active
      inflammation appear to have decreased levels of IgA. An inverse correlation
      between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation
      compromises the mucosal IgA defence and renders the mucosa susceptible to further
      damage.

PMID- 10087250
TI  - Coronary sinus adrenomedullin rises in response to myocardial injury.
AB  - Human adrenomedullin (ADM), a peptide comprising 52 amino acids, is a circulating
      hormone with vasodilator properties. We have evaluated its release by the heart
      following ischaemic myocardial damage, as indicated by elevated levels of the
      cardiospecific protein troponin-T (Tn-T) during cardiopulmonary bypass. ADM
      (pg/ml) and Tn-T (ng/ml) were measured in coronary sinus blood before and after
      aortic cross-clamp and in venous blood 6 h after surgery in 22 coronary-bypass
      patients. Based on the pre- and post-clamp Tn-T levels in the coronary sinus, the
      patients were divided into group I (no change; n=10) and group II (two times
      increase; n=12). Baseline ADM (362.7+/-106.2 and 303+/-58.7 pg/ml in groups I and
      II respectively; means+/-S.D.) and Tn-T (0.66+/-0.14 and 0.57+/-0.13 ng/ml
      respectively) levels were similar in both groups. In group I, the post-clamp ADM
      (317.6+/-80.8 pg/ml) and Tn-T (0.68+/-0.15 ng/ml) levels did not change
      significantly. In group II, the post-clamp ADM levels rose significantly above
      the baseline, mimicking the change in Tn-T (ADM, 541.4+/-89.4 pg/ml; Tn-T, 1.37+/
      0.31 ng/ml; P=0.009). After 6 h, the systemic Tn-T levels were similar in both
      groups (2. 09+/-0.44 and 1.95+/-0.52 ng/ml in groups I and II respectively). We
      suggest that: (1) minor degrees of myocardial ischaemic damage result in release
      of ADM by the heart, and (2) ADM may play a protective role in the myocardium
      during an ischaemic insult. This suggests a possible therapeutic role for ADM in
      the management of intra-operative myocardial ischaemia.

PMID- 10087251
TI  - Is normal pregnancy atherogenic?
AB  - Serum cholesterol, triacylglycerols and low-density lipoprotein (LDL)
      subfractions were determined in 120 primagravid women during normal gestation (40
      in each trimester) and in 20 non-pregnant age-matched controls. LDL subfractions
      were determined by PAGE, and an LDL score was calculated. The higher the score,
      the smaller the subfractions. The objective of the study was to determine the
      effects of the hyperlipidaemia, high oestrogen concentrations and insulin
      resistance known to exist in normal pregnancy on LDL subfraction formation.
      Pregnant women had an increased mean serum cholesterol concentration [5.78 (S.D.
      1.09) mmol/l] in the first trimester compared with the non-pregnant controls
      [5.11 (0.77) mmol/l; P<0.01]. The serum cholesterol concentration increased
      progressively throughout gestation to a mean of 8.14 (1.39) mmol/l in the third
      trimester (P<0.001 compared with the second trimester). Triacylglycerol
      concentrations in the first trimester were similar to those of controls, and
      there was a non-significant increase by the second trimester to 1.32 (0.44)
      mmol/l. However, by the third trimester the mean triacylglycerol concentration
      had doubled [2.58 (0.98) mmol/l; P<0.001 compared with the first and second
      trimester]. During gestation the LDL score increased dramatically, from 1.17
      (0.39) during the first trimester to 2.01 (0.37) in the second trimester
      (P<0.001) to 2.73 (0.48) in the third trimester (P<0.001 compared with the second
      trimester). Thus an atherogenic lipid profile develops during normal gestation.
      The significance of these changes remains unclear, but thay may have important
      implications for mother and foetus.

PMID- 10087252
TI  - Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic
      renal failure.
AB  - Normal pregnancy is associated with an increase in serum parathyroid hormone and
      1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones
      in chronic renal failure (CRF) is unknown. The present work was undertaken to
      study the changes of serum immunoreactive parathyroid hormone (iPTH) and
      calcitriol in pregnant rats with CRF. The following experimental groups were
      studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized
      pregnant rats at day 20-21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks
      after delivery) and their respective sham-operated control groups: N1, N2 and N3.
      The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH
      (100+/-18 pg/ml) and low calcitriol levels (10.6+/-4.3 pg/ml) compared with
      normal rats [N1: 14+/-2.5 pg/ml (P<0.001) and 18.2+/-4.2 pg/ml (P<0.01)
      respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of
      serum iPTH levels (18.2+/-5.41 pg/ml), which was associated with a parallel
      increase in serum calcitriol (29.4+/-8.0 pg/ml) similar to that in pregnancy of
      normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had
      high serum iPTH (87+/-17 pg/ml) and low calcitriol levels (9.3+/-1.2 pg/ml),
      similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded
      that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably
      by the increased level of calcitriol synthesized by the feto-placental unit.

PMID- 10087253
TI  - Lysophosphatidic acid and mesangial cells: implications for renal diseases.
AB  - The last decade has witnessed a phenomenal increase in our understanding of the
      biological role of lysophosphatidic acid (LPA) and has led to an appreciation of
      this critical serum-derived growth factor released from platelets. We herein
      summarize recent observations that collectively support the hypothesis that LPA
      may play a key role in the pathogenesis of initiation and progression of
      proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell
      proliferation in combination with platelet-derived growth factor in primary
      culture. The mechanism of co-mitogenesis is likely to be mediated by the
      prolonged activation of mitogen-activated protein kinase which is stimulated by
      platelet-derived growth factor and LPA through different mechanisms. LPA
      contracts cultured mesangial cells and has properties in common with other
      pressor molecules including mobilization of intracellular Ca2+ and promotion of
      Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA
      has been identified in isolated glomeruli dissected from renal biopsy samples of
      patients with IgA nephropathy. All of these facts have led us to postulate that
      LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic
      action contribute to the pathological process of mesangial proliferative
      glomerulonephritis. The possible production of LPA as an autocrine factor from
      mesangial cells themselves has also been discussed.

PMID- 10087254
TI  - Reproducibility of baroreflex sensitivity measured by a neck suction method.

PMID- 10087255
TI  - Roles of LAP2 proteins in nuclear assembly and DNA replication: truncated
      LAP2beta proteins alter lamina assembly, envelope formation, nuclear size, and
      DNA replication efficiency in Xenopus laevis extracts.
AB  - Humans express three major splicing isoforms of LAP2, a lamin- and chromatin
      binding nuclear protein. LAP2beta and gamma are integral membrane proteins,
      whereas alpha is intranuclear. When truncated recombinant human LAP2beta proteins
      were added to cell-free Xenopus laevis nuclear assembly reactions at high
      concentrations, a domain common to all LAP2 isoforms (residues 1-187) inhibited
      membrane binding to chromatin, whereas the chromatin- and lamin-binding region
      (residues 1-408) inhibited chromatin expansion. At lower concentrations of the
      common domain, membranes attached to chromatin with a unique scalloped
      morphology, but these nuclei neither accumulated lamins nor replicated. At lower
      concentrations of the chromatin- and lamin-binding region, nuclear envelopes and
      lamins assembled, but nuclei failed to enlarge and replicated on average 2. 5
      fold better than controls. This enhancement was not due to rereplication, as
      shown by density substitution experiments, suggesting the hypothesis that
      LAP2beta is a downstream effector of lamina assembly in promoting replication
      competence. Overall, our findings suggest that LAP2 proteins mediate membrane
      chromatin attachment and lamina assembly, and may promote replication by
      influencing chromatin structure.

PMID- 10087256
TI  - A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186
      kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.
AB  - The mammalian nuclear pore complex (NPC) is comprised of approximately 50 unique
      proteins, collectively known as nucleoporins. Through fractionation of rat liver
      nuclei, we have isolated >30 potentially novel nucleoporins and have begun a
      systematic characterization of these proteins. Here, we present the
      characterization of Nup96, a novel nucleoporin with a predicted molecular mass of
      96 kD. Nup96 is generated through an unusual biogenesis pathway that involves
      synthesis of a 186-kD precursor protein. Proteolytic cleavage of the precursor
      yields two nucleoporins: Nup98, a previously characterized GLFG-repeat containing
      nucleoporin, and Nup96. Mutational and functional analyses demonstrate that both
      the Nup98-Nup96 precursor and the previously characterized Nup98 (synthesized
      independently from an alternatively spliced mRNA) are proteolytically cleaved in
      vivo. This biogenesis pathway for Nup98 and Nup96 is evolutionarily conserved, as
      the putative Saccharomyces cerevisiae homologues, N-Nup145p and C-Nup145p, are
      also produced through proteolytic cleavage of a precursor protein. Using
      immunoelectron microscopy, Nup96 was localized to the nucleoplasmic side of the
      NPC, at or near the nucleoplasmic basket. The correct targeting of both Nup96 and
      Nup98 to the nucleoplasmic side of the NPC was found to be dependent on
      proteolytic cleavage, suggesting that the cleavage process may regulate NPC
      assembly. Finally, by biochemical fractionation, a complex containing Nup96,
      Nup107, and at least two Sec13- related proteins was identified, revealing that a
      major sub-complex of the NPC is conserved between yeast and mammals.

PMID- 10087257
TI  - Dynamics of myoblast transplantation reveal a discrete minority of precursors
      with stem cell-like properties as the myogenic source.
AB  - Myoblasts, the precursors of skeletal muscle fibers, can be induced to withdraw
      from the cell cycle and differentiate in vitro. Recent studies have also
      identified undifferentiated subpopulations that can self-renew and generate
      myogenic cells (Baroffio, A., M. Hamann, L. Bernheim, M.-L. Bochaton-Pillat, G.
      Gabbiani, and C.R. Bader. 1996. Differentiation. 60:47-57; Yoshida, N., S.
      Yoshida, K. Koishi, K. Masuda, and Y. Nabeshima. 1998. J. Cell Sci. 111:769-779).
      Cultured myoblasts can also differentiate and contribute to repair and new muscle
      formation in vivo, a capacity exploited in attempts to develop myoblast
      transplantation (MT) for genetic modification of adult muscle. Our studies of the
      dynamics of MT demonstrate that cultures of myoblasts contain distinct
      subpopulations defined by their behavior in vitro and divergent responses to
      grafting. By comparing a genomic and a semiconserved marker, we have followed the
      fate of myoblasts transplanted into muscles of dystrophic mice, finding that the
      majority of the grafted cells quickly die and only a minority are responsible for
      new muscle formation. This minority is behaviorally distinct, slowly dividing in
      tissue culture, but rapidly proliferative after grafting, suggesting a
      subpopulation with stem cell-like characteristics.

PMID- 10087258
TI  - minifly, a Drosophila gene required for ribosome biogenesis.
AB  - We report here the genetic, molecular, and functional characterization of the
      Drosophila melanogaster minifly (mfl) gene. Genetic analysis shows that mfl is
      essential for Drosophila viability and fertility. While P-element induced total
      loss-of-function mutations cause lethality, mfl partial loss-of-function
      mutations cause pleiotropic defects, such as extreme reduction of body size,
      developmental delay, hatched abdominal cuticle, and reduced female fertility.
      Morphological abnormalities characteristic of apoptosis are found in the ovaries,
      and a proportion of eggs laid by mfl mutant females degenerates during
      embryogenesis. We show that mfl encodes an ubiquitous nucleolar protein that
      plays a central role in ribosomal RNA processing and pseudouridylation, whose
      known eukaryotic homologues are yeast Cfb5p, rat NAP57 and human dyskerin,
      encoded by the gene responsible for the X-linked dyskeratosis congenita disease.
      mfl genetic analysis represents the first in vivo functional characterization of
      a member of this highly conserved gene family from higher eukaryotes. In
      addition, we report that mfl hosts an intron encoded box H/ACA snoRNA gene, the
      first member of this class of snoRNAs identified so far from Drosophila.

PMID- 10087259
TI  - Golgi structure in three dimensions: functional insights from the normal rat
      kidney cell.
AB  - Three-dimensional reconstructions of portions of the Golgi complex from
      cryofixed, freeze-substituted normal rat kidney cells have been made by dual
      axis, high-voltage EM tomography at approximately 7-nm resolution. The
      reconstruction shown here ( approximately 1 x 1 x 4 microm3) contains two stacks
      of seven cisternae separated by a noncompact region across which bridges connect
      some cisternae at equivalent levels, but none at nonequivalent levels. The rest
      of the noncompact region is filled with both vesicles and polymorphic membranous
      elements. All cisternae are fenestrated and display coated buds. They all have
      about the same surface area, but they differ in volume by as much as 50%. The
      trans-most cisterna produces exclusively clathrin-coated buds, whereas the others
      display only nonclathrin coated buds. This finding challenges traditional views
      of where sorting occurs within the Golgi complex. Tubules with budding profiles
      extend from the margins of both cis and trans cisternae. They pass beyond
      neighboring cisternae, suggesting that these tubules contribute to traffic to
      and/or from the Golgi. Vesicle-filled "wells" open to both the cis and lateral
      sides of the stacks. The stacks of cisternae are positioned between two types of
      ER, cis and trans. The cis ER lies adjacent to the ER-Golgi intermediate
      compartment, which consists of discrete polymorphic membranous elements layered
      in front of the cis-most Golgi cisterna. The extensive trans ER forms close
      contacts with the two trans-most cisternae; this apposition may permit direct
      transfer of lipids between ER and Golgi membranes. Within 0.2 microm of the
      cisternae studied, there are 394 vesicles (8 clathrin coated, 190 nonclathrin
      coated, and 196 noncoated), indicating considerable vesicular traffic in this
      Golgi region. Our data place structural constraints on models of trafficking to,
      through, and from the Golgi complex.

PMID- 10087260
TI  - Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2
      dependent protein import into peroxisomes.
AB  - Pex13p is the putative docking protein for peroxisomal targeting signal 1 (PTS1)
      dependent protein import into peroxisomes. Pex14p interacts with both the PTS1-
      and PTS2-receptor and may represent the point of convergence of the PTS1- and
      PTS2-dependent protein import pathways. We report the involvement of Pex13p in
      peroxisomal import of PTS2-containing proteins. Like Pex14p, Pex13p not only
      interacts with the PTS1-receptor Pex5p, but also with the PTS2-receptor Pex7p;
      however, this association may be direct or indirect. In support of distinct
      peroxisomal binding sites for Pex7p, the Pex7p/Pex13p and Pex7p/ Pex14p complexes
      can form independently. Genetic evidence for the interaction of Pex7p and Pex13p
      is provided by the observation that overexpression of Pex13p suppresses a loss of
      function mutant of Pex7p. Accordingly, we conclude that Pex7p and Pex13p
      functionally interact during PTS2-dependent protein import into peroxisomes. NH2
      terminal regions of Pex13p are required for its interaction with the PTS2
      receptor while the COOH-terminal SH3 domain alone is sufficient to mediate its
      interaction with the PTS1-receptor. Reinvestigation of the topology revealed both
      termini of Pex13p to be oriented towards the cytosol. We also found Pex13p to be
      required for peroxisomal association of Pex14p, yet the SH3 domain of Pex13p may
      not provide the only binding site for Pex14p at the peroxisomal membrane.

PMID- 10087261
TI  - Recombinant major vault protein is targeted to neuritic tips of PC12 cells.
AB  - The major vault protein (MVP) is the predominant constituent of ubiquitous,
      evolutionarily conserved large cytoplasmic ribonucleoprotein particles of unknown
      function. Vaults are multimeric protein complexes with several copies of an
      untranslated RNA. Double labeling employing laser-assisted confocal microscopy
      and indirect immunofluorescence demonstrates partial colocalization of vaults
      with cytoskeletal elements in Chinese hamster ovary (CHO) and nerve growth factor
      (NGF)-treated neuronlike PC12 cells. Transfection of CHO and PC12 cells with a
      cDNA encoding the rat major vault protein containing a vesicular stomatitis virus
      glycoprotein epitope tag demonstrates that the recombinant protein is sorted into
      vault particles and targeted like endogenous MVPs. In neuritic extensions of
      differentiated PC12 cells, there is an almost complete overlap of the
      distribution of microtubules and vaults. A pronounced colocalization of vaults
      with filamentous actin can be seen in the tips of neurites. Moreover, in NGF
      treated PC12 cells the location of vaults partially coincides with vesicular
      markers. Within the terminal tips of neurites vaults are located near secretory
      organelles. Our observations suggest that the vault particles are transported
      along cytoskeletal-based cellular tracks.

PMID- 10087262
TI  - Fission yeast alpha-glucan synthase Mok1 requires the actin cytoskeleton to
      localize the sites of growth and plays an essential role in cell morphogenesis
      downstream of protein kinase C function.
AB  - In fission yeast protein kinase C homologues (Pck1 and Pck2) are essential for
      cell morphogenesis. We have isolated mok1(+) in a genetic screen to identify
      downstream effectors for Pck1/2. mok1(+) is essential for viability and encodes a
      protein that has several membrane-spanning domains and regions homologous to
      glucan metabolic enzymes. mok1 mutant shows abnormal cell shape, randomization of
      F-actin and weak cell wall. Biochemical analysis shows that Mok1 appears to have
      alpha-glucan synthase activity. Mok1 localization undergoes dramatic alteration
      during the cell cycle. It localizes to the growing tips in interphase, the medial
      ring upon mitosis, a double ring before and dense dot during cytokinesis. Double
      immunofluorescence staining shows that Mok1 exists in close proximity to actin.
      The subcellular localization of Mok1 is dependent upon the integrity of the F
      actin cytoskeleton. Conversely, overexpression of mok1(+) blocks the
      translocation of cortical actin from one end of the cell to the other. pck2
      mutant is synthetically lethal with mok1 mutant, delocalizes Mok1 and shows a
      lower level of alpha-glucan. These results indicate that Mok1 plays a crucial
      role in cell morphogenesis interdependently of the actin cytoskeleton and works
      as one of downstream effectors for Pck1/2.

PMID- 10087263
TI  - A Cdc24p-Far1p-Gbetagamma protein complex required for yeast orientation during
      mating.
AB  - Oriented cell growth requires the specification of a site for polarized growth
      and subsequent orientation of the cytoskeleton towards this site. During mating,
      haploid Saccharomyces cerevisiae cells orient their growth in response to a
      pheromone gradient overriding an internal landmark for polarized growth, the bud
      site. This response requires Cdc24p, Far1p, and a heterotrimeric G-protein. Here
      we show that a two- hybrid interaction between Cdc24p and Gbeta requires Far1p
      but not pheromone-dependent MAP-kinase signaling, indicating Far1p has a role in
      regulating the association of Cdc24p and Gbeta. Binding experiments demonstrate
      that Cdc24p, Far1p, and Gbeta form a complex in which pairwise interactions can
      occur in the absence of the third protein. Cdc24p localizes to sites of polarized
      growth suggesting that this complex is localized. In the absence of CDC24-FAR1
      mediated chemotropism, a bud site selection protein, Bud1p/Rsr1p, is essential
      for morphological changes in response to pheromone. These results suggest that
      formation of a Cdc24p-Far1p-Gbetagamma complex functions as a landmark for
      orientation of the cytoskeleton during growth towards an external signal.

PMID- 10087264
TI  - Novel protein kinases Ark1p and Prk1p associate with and regulate the cortical
      actin cytoskeleton in budding yeast.
AB  - Ark1p (actin regulating kinase 1) was identified as a yeast protein that binds to
      Sla2p, an evolutionarily conserved cortical actin cytoskeleton protein. Ark1p and
      a second yeast protein, Prk1p, contain NH2-terminal kinase domains that are 70%
      identical. Together with six other putative kinases from a number of organisms,
      these proteins define a new protein kinase family that we have named the Ark
      family. Lack of both Ark1p and Prk1p resulted in the formation of large
      cytoplasmic actin clumps and severe defects in cell growth. These defects were
      rescued by wild-type, but not by kinase-dead versions of the proteins. Elevated
      levels of either Ark1p or Prk1p caused a number of actin and cell morphological
      defects that were not observed when the kinase-dead versions were overexpressed
      instead. Ark1p and Prk1p were shown to localize to actin cortical patches, making
      these two kinases the first signaling proteins demonstrated to be patch
      components. These results suggest that Ark1p and Prk1p may be downstream
      effectors of signaling pathways that control actin patch organization and
      function. Furthermore, results of double-mutant analyses suggest that Ark1p and
      Prk1p function in overlapping but distinct pathways that regulate the cortical
      actin cytoskeleton.

PMID- 10087265
TI  - Differential regulation of the Kar3p kinesin-related protein by two associated
      proteins, Cik1p and Vik1p.
AB  - The mechanisms by which kinesin-related proteins interact with other proteins to
      carry out specific cellular processes is poorly understood. The kinesin-related
      protein, Kar3p, has been implicated in many microtubule functions in yeast. Some
      of these functions require interaction with the Cik1 protein (Page, B.D., L.L.
      Satterwhite, M.D. Rose, and M. Snyder. 1994. J. Cell Biol. 124:507-519). We have
      identified a Saccharomyces cerevisiae gene, named VIK1, encoding a protein with
      sequence and structural similarity to Cik1p. The Vik1 protein is detected in
      vegetatively growing cells but not in mating pheromone-treated cells. Vik1p
      physically associates with Kar3p in a complex separate from that of the Kar3p
      Cik1p complex. Vik1p localizes to the spindle-pole body region in a Kar3p
      dependent manner. Reciprocally, concentration of Kar3p at the spindle poles
      during vegetative growth requires the presence of Vik1p, but not Cik1p.
      Phenotypic analysis suggests that Cik1p and Vik1p are involved in different Kar3p
      functions. Disruption of VIK1 causes increased resistance to the microtubule
      depolymerizing drug benomyl and partially suppresses growth defects of cik1Delta
      mutants. The vik1Delta and kar3Delta mutations, but not cik1Delta, partially
      suppresses the temperature-sensitive growth defect of strains lacking the
      function of two other yeast kinesin-related proteins, Cin8p and Kip1p. Our
      results indicate that Kar3p forms functionally distinct complexes with Cik1p and
      Vik1p to participate in different microtubule-mediated events within the same
      cell.

PMID- 10087266
TI  - Rho GTPases control polarity, protrusion, and adhesion during cell movement.
AB  - Cell movement is essential during embryogenesis to establish tissue patterns and
      to drive morphogenetic pathways and in the adult for tissue repair and to direct
      cells to sites of infection. Animal cells move by crawling and the driving force
      is derived primarily from the coordinated assembly and disassembly of actin
      filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of
      actin filaments and we have analyzed their contributions to the movement of
      primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential
      for the protrusion of lamellipodia and for forward movement. Cdc42 is required to
      maintain cell polarity, which includes the localization of lamellipodial activity
      to the leading edge and the reorientation of the Golgi apparatus in the direction
      of movement. Rho is required to maintain cell adhesion during movement, but
      stress fibers and focal adhesions are not required. Finally, Ras regulates focal
      adhesion and stress fiber turnover and this is essential for cell movement. We
      conclude that the signal transduction pathways controlled by the four small
      GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.

PMID- 10087267
TI  - Role of proteins of the Ena/VASP family in actin-based motility of Listeria
      monocytogenes.
AB  - Intracellular propulsion of Listeria monocytogenes is the best understood form of
      motility dependent on actin polymerization. We have used in vitro motility assays
      of Listeria in platelet and brain extracts to elucidate the function of the focal
      adhesion proteins of the Ena (Drosophila Enabled)/VASP (vasodilator-stimulated
      phosphoprotein) family in actin-based motility. Immunodepletion of VASP from
      platelet extracts and of Evl (Ena/VASP-like protein) from brain extracts of Mena
      knockout (-/-) mice combined with add-back of recombinant (bacterial or
      eukaryotic) VASP and Evl show that VASP, Mena, and Evl play interchangeable roles
      and are required to transform actin polymerization into active movement and
      propulsive force. The EVH1 (Ena/VASP homology 1) domain of VASP is in slow
      association-dissociation equilibrium high-affinity binding to the zyxin
      homologous, proline-rich region of ActA. VASP also interacts with F-actin via its
      COOH-terminal EVH2 domain. Hence VASP/ Ena/Evl link the bacterium to the actin
      tail, which is required for movement. The affinity of VASP for F-actin is
      controlled by phosphorylation of serine 157 by cAMP-dependent protein kinase.
      Phospho-VASP binds with high affinity (0.5 x 10(8) M-1); dephospho-VASP binds 40
      fold less tightly. We propose a molecular ratchet model for insertional
      polymerization of actin, within which frequent attachment-detachment of VASP to F
      actin allows its sliding along the growing filament.

PMID- 10087268
TI  - Extensive but coordinated reorganization of the membrane skeleton in myofibers of
      dystrophic (mdx) mice.
AB  - We used immunofluorescence techniques and confocal imaging to study the
      organization of the membrane skeleton of skeletal muscle fibers of mdx mice,
      which lack dystrophin. beta-Spectrin is normally found at the sarcolemma in
      costameres, a rectilinear array of longitudinal strands and elements overlying Z
      and M lines. However, in the skeletal muscle of mdx mice, beta-spectrin tends to
      be absent from the sarcolemma over M lines and the longitudinal strands may be
      disrupted or missing. Other proteins of the membrane and associated cytoskeleton,
      including syntrophin, beta-dystroglycan, vinculin, and Na,K-ATPase are also
      concentrated in costameres, in control myofibers, and mdx muscle. They also
      distribute into the same altered sarcolemmal arrays that contain beta-spectrin.
      Utrophin, which is expressed in mdx muscle, also codistributes with beta-spectrin
      at the mutant sarcolemma. By contrast, the distribution of structural and
      intracellular membrane proteins, including alpha-actinin, the Ca-ATPase and
      dihydropyridine receptors, is not affected, even at sites close to the
      sarcolemma. Our results suggest that in myofibers of the mdx mouse, the membrane-
      associated cytoskeleton, but not the nearby myoplasm, undergoes widespread
      coordinated changes in organization. These changes may contribute to the
      fragility of the sarcolemma of dystrophic muscle.

PMID- 10087269
TI  - Endocytic sorting of lipid analogues differing solely in the chemistry of their
      hydrophobic tails.
AB  - To understand the mechanisms for endocytic sorting of lipids, we investigated the
      trafficking of three lipid-mimetic dialkylindocarbocyanine (DiI) derivatives,
      DiIC16(3) (1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate),
      DiIC12(3) (1,1'- didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate),
      and FAST DiI (1,1'-dilinoleyl-3,3,3', 3'-tetramethylindocarbocyanine
      perchlorate), in CHO cells by quantitative fluorescence microscopy. All three
      DiIs have the same head group, but differ in their alkyl tail length or
      unsaturation; these differences are expected to affect their distribution in
      membrane domains of varying fluidity or curvature. All three DiIs initially enter
      sorting endosomes containing endocytosed transferrin. DiIC16(3), with two long 16
      carbon saturated tails is then delivered to late endosomes, whereas FAST DiI,
      with two cis double bonds in each tail, and DiIC12(3), with saturated but shorter
      (12-carbon) tails, are mainly found in the endocytic recycling compartment. We
      also find that DiOC16(3) (3,3'- dihexadecyloxacarbocyanine perchlorate) and FAST
      DiO (3, 3'-dilinoleyloxacarbocyanine perchlorate) behave similarly to their DiI
      counterparts. Furthermore, whereas a phosphatidylcholine analogue with a BODIPY
      (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophore attached at the end of a
      5-carbon acyl chain is delivered efficiently to the endocytic recycling
      compartment, a significant fraction of another derivative with BODIPY attached to
      a 12-carbon acyl chain entered late endosomes. Our results thus suggest that
      endocytic organelles can sort membrane components efficiently based on their
      preference for association with domains of varying characteristics.

PMID- 10087270
TI  - A role for caveolin and the urokinase receptor in integrin-mediated adhesion and
      signaling.
AB  - The assembly of signaling molecules surrounding the integrin family of adhesion
      receptors remains poorly understood. Recently, the membrane protein caveolin was
      found in complexes with beta1 integrins. Caveolin binds cholesterol and several
      signaling molecules potentially linked to integrin function, e.g., Src family
      kinases, although caveolin has not been directly implicated in integrin-dependent
      adhesion. Here we report that depletion of caveolin by antisense methodology in
      kidney 293 cells disrupts the association of Src kinases with beta1 integrins
      resulting in loss of focal adhesion sites, ligand-induced focal adhesion kinase
      (FAK) phosphorylation, and adhesion. The nonintegrin urokinase receptor (uPAR)
      associates with and stabilizes beta1 integrin/caveolin complexes. Depletion of
      caveolin in uPAR-expressing 293 cells also disrupts uPAR/integrin complexes and
      uPAR-dependent adhesion. Further, beta1 integrin/caveolin complexes could be
      disassociated by uPAR-binding peptides in both uPAR-transfected 293 cells and
      human vascular smooth muscle cells. Disruption of complexes by peptides in intact
      smooth muscle cells blocks the association of Src family kinases with beta1
      integrins and markedly impairs their migration on fibronectin. We conclude that
      ligand-induced signaling necessary for normal beta1 integrin function requires
      caveolin and is regulated by uPAR. Caveolin and uPAR may operate within adhesion
      sites to organize kinase-rich lipid domains in proximity to integrins, promoting
      efficient signal transduction.

PMID- 10087271
TI  - Quantitative changes in integrin and focal adhesion signaling regulate myoblast
      cell cycle withdrawal.
AB  - We previously demonstrated contrasting roles for integrin alpha subunits and
      their cytoplasmic domains in controlling cell cycle withdrawal and the onset of
      terminal differentiation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and
      A.F. Horwitz. 1996. J. Cell Biol. 133:169-184). Ectopic expression of the
      integrin alpha5 or alpha6A subunit in primary quail myoblasts either decreases or
      enhances the probability of cell cycle withdrawal, respectively. In this study,
      we addressed the mechanisms by which changes in integrin alpha subunit ratios
      regulate this decision. Ectopic expression of truncated alpha5 or alpha6A
      indicate that the alpha5 cytoplasmic domain is permissive for the proliferative
      pathway whereas the COOH-terminal 11 amino acids of alpha6A cytoplasmic domain
      inhibit proliferation and promote differentiation. The alpha5 and alpha6A
      cytoplasmic domains do not appear to initiate these signals directly, but instead
      regulate beta1 signaling. Ectopically expressed IL2R-alpha5 or IL2R-alpha6A have
      no detectable effect on the myoblast phenotype. However, ectopic expression of
      the beta1A integrin subunit or IL2R-beta1A, autonomously inhibits differentiation
      and maintains a proliferative state. Perturbing alpha5 or alpha6A ratios also
      significantly affects activation of beta1 integrin signaling pathways. Ectopic
      alpha5 expression enhances expression and activation of paxillin as well as
      mitogen-activated protein (MAP) kinase with little effect on focal adhesion
      kinase (FAK). In contrast, ectopic alpha6A expression suppresses FAK and MAP
      kinase activation with a lesser effect on paxillin. Ectopic expression of wild
      type and mutant forms of FAK, paxillin, and MAP/erk kinase (MEK) confirm these
      correlations. These data demonstrate that (a) proliferative signaling (i.e.,
      inhibition of cell cycle withdrawal and the onset of terminal differentiation)
      occurs through the beta1A subunit and is modulated by the alpha subunit
      cytoplasmic domains; (b) perturbing alpha subunit ratios alters paxillin
      expression and phosphorylation and FAK and MAP kinase activation; (c)
      quantitative changes in the level of adhesive signaling through integrins and
      focal adhesion components regulate the decision of myoblasts to withdraw from the
      cell cycle, in part via MAP kinase.

PMID- 10087272
TI  - Functional domains of alpha-catenin required for the strong state of cadherin
      based cell adhesion.
AB  - The interaction of cadherin-catenin complex with the actin-based cytoskeleton
      through alpha-catenin is indispensable for cadherin-based cell adhesion activity.
      We reported previously that E-cadherin-alpha-catenin fusion molecules showed cell
      adhesion and cytoskeleton binding activities when expressed in nonepithelial L
      cells. Here, we constructed deletion mutants of E-cadherin-alpha-catenin fusion
      molecules lacking various domains of alpha-catenin and introduced them into L
      cells. Detailed analysis identified three distinct functional domains of alpha
      catenin: a vinculin/alpha-actinin-binding domain, a ZO-1-binding domain, and an
      adhesion-modulation domain. Furthermore, cell dissociation assay revealed that
      the fusion molecules containing the ZO-1-binding domain in addition to the
      adhesion-modulation domain conferred the strong state of cell adhesion activity
      on transfectants, although those lacking the ZO-1-binding domain conferred only
      the weak state. The disorganization of actin-based cytoskeleton by cytochalasin D
      treatment shifted the cadherin-based cell adhesion from the strong to the weak
      state. In the epithelial cells, where alpha-catenin was not precisely colocalized
      with ZO-1, the ZO-1-binding domain did not completely support the strong state of
      cell adhesion activity. Our studies showed that the interaction of alpha-catenin
      with the actin-based cytoskeleton through the ZO-1-binding domain is required for
      the strong state of E-cadherin-based cell adhesion activity.

PMID- 10087273
TI  - PTPmu regulates N-cadherin-dependent neurite outgrowth.
AB  - Cell adhesion is critical to the establishment of proper connections in the
      nervous system. Some receptor-type protein tyrosine phosphatases (RPTPs) have
      adhesion molecule-like extracellular segments with intracellular tyrosine
      phosphatase domains that may transduce signals in response to adhesion. PTPmu is
      a RPTP that mediates cell aggregation and is expressed at high levels in the
      nervous system. In this study, we demonstrate that PTPmu promotes neurite
      outgrowth of retinal ganglion cells when used as a culture substrate. In
      addition, PTPmu was found in a complex with N-cadherin in retinal cells. To
      determine the physiological significance of the association between PTPmu and N
      cadherin, the expression level and enzymatic activity of PTPmu were perturbed in
      retinal explant cultures. Downregulation of PTPmu expression through antisense
      techniques resulted in a significant decrease in neurite outgrowth on an N
      cadherin substrate, whereas there was no effect on laminin or L1-dependent
      neurite outgrowth. The overexpression of a catalytically inactive form of PTPmu
      significantly decreased neurite outgrowth on N-cadherin. These data indicate that
      PTPmu specifically regulates signals required for neurites to extend on an N
      cadherin substrate, implicating reversible tyrosine phosphorylation in the
      control of N-cadherin function. Together, these results suggest that PTPmu plays
      a dual role in the regulation of neurite outgrowth.

PMID- 10087274
TI  - Extracellular matrix regulates apoptosis in mammary epithelium through a control
      on insulin signaling.
AB  - Adherent epithelial cells require interactions with the extracellular matrix for
      their survival, though the mechanism is ill-defined. In long term cultures of
      primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not
      collagen I suppresses apoptosis, indicating that adhesion survival signals are
      specific in their response (. J. Cell Sci. 109:631-642). We now demonstrate that
      the signal from BM is mediated by integrins and requires both the alpha6 and
      beta1 subunits. In addition, a hormonal signal from insulin or insulin-like
      growth factors, but not hydrocortisone or prolactin, is necessary to suppress
      mammary cell apoptosis, indicating that BM and soluble factors cooperate in
      survival signaling. Insulin induced autophosphorylation of its receptor whether
      mammary cells were cultured on collagen I or BM substrata. However, both the
      tyrosine phosphorylation of insulin receptor substrate-1 and its association with
      phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the
      phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B.
      These results suggest a novel extracellular matrix-dependent restriction point in
      insulin signaling in mammary epithelial cells. The proximal signal transduction
      event of insulin receptor phosphorylation is not dependent on extracellular
      matrix, but the activation of downstream effectors requires adhesion to BM. Since
      phosphatidylinositol 3-kinase was required for mammary epithelial cell survival,
      we propose that a possible mechanism for BM-mediated suppression of apoptosis is
      through its facilitative effects on insulin signaling.

PMID- 10087276
TI  - Thirty Years of Energy-Dispersive Spectrometry in Microanalysis: Introduction.

PMID- 10087275
TI  - Genetic analysis of collagen Q: roles in acetylcholinesterase and
      butyrylcholinesterase assembly and in synaptic structure and function.
AB  - Acetylcholinesterase (AChE) occurs in both asymmetric forms, covalently
      associated with a collagenous subunit called Q (ColQ), and globular forms that
      may be either soluble or membrane associated. At the skeletal neuromuscular
      junction, asymmetric AChE is anchored to the basal lamina of the synaptic cleft,
      where it hydrolyzes acetylcholine to terminate synaptic transmission. AChE has
      also been hypothesized to play developmental roles in the nervous system, and
      ColQ is also expressed in some AChE-poor tissues. To seek roles of ColQ and AChE
      at synapses and elsewhere, we generated ColQ-deficient mutant mice. ColQ-/- mice
      completely lacked asymmetric AChE in skeletal and cardiac muscles and brain; they
      also lacked asymmetric forms of the AChE homologue, butyrylcholinesterase. Thus,
      products of the ColQ gene are required for assembly of all detectable asymmetric
      AChE and butyrylcholinesterase. Surprisingly, globular AChE tetramers were also
      absent from neonatal ColQ-/- muscles, suggesting a role for the ColQ gene in
      assembly or stabilization of AChE forms that do not themselves contain a
      collagenous subunit. Histochemical, immunohistochemical, toxicological, and
      electrophysiological assays all indicated absence of AChE at ColQ-/-
      neuromuscular junctions. Nonetheless, neuromuscular function was initially
      robust, demonstrating that AChE and ColQ do not play obligatory roles in early
      phases of synaptogenesis. Moreover, because acute inhibition of synaptic AChE is
      fatal to normal animals, there must be compensatory mechanisms in the mutant that
      allow the synapse to function in the chronic absence of AChE. One structural
      mechanism appears to be a partial ensheathment of nerve terminals by Schwann
      cells. Compensation was incomplete, however, as animals lacking ColQ and synaptic
      AChE failed to thrive and most died before they reached maturity.

PMID- 10087277
TI  - Going Nondispersive.
AB  - : The energy-dispersive Si(Li) X-ray spectrometer, introduced 30 years ago into
      electron probe microanalysis (EPMA) by R. Fitzgerald et al., has profoundly
      affected the development of microanalysis. It offers many advantages over the
      wavelength-dispersive crystal spectrometer. It has no moving parts and covers the
      full energy range of interest in EPMA. There is no defocusing over large
      distances on the specimen, the efficiency of the device is high, varies slowly
      and continuously with atomic number, and can be predicted fairly accurately, and,
      most importantly, all emission lines are detected and can be observed
      simultaneously. The one remaining disadvantage of the Si(Li) spectrometer is its
      poorer energy resolution. Solid-state detection devices now under development
      promise to achieve resolution comparable to that of the crystal spectrometer.

PMID- 10087278
TI  - Energy-Dispersive Spectrometry from Then until Now: A Chronology of Innovation.
AB  - : As part of the Microbeam Analysis Society (MAS) symposium marking 30 years of
      energy-dispersive spectrometry (EDS), this article reviews many innovations in
      the field over those years. Innovations that added a capability previously not
      available to the microanalyst are chosen for further description. Included are
      innovations in both X-ray microanalysis and digital imaging using the EDS
      analyzer.

PMID- 10087279
TI  - Impact of Energy-Dispersive Spectrometry in Materials Science Microanalysis.
AB  - : X-ray microanalysis of materials using energy-dispersive spectrometry (EDS) has
      made the greatest impact in studies of compositional changes at atomic-level
      interfaces. The small physical dimensions of the silicon detector make EDS the X
      ray analyzer of choice for analytical transmission electron microscopy (AEM). X
      ray analysis of thin foils in the AEM has contributed to our understanding of
      elemental segregation to interphase interfaces and grain boundaries, as well as
      other planar defects. Measurement of atomic diffusion on a small scale close to
      interphase interfaces has permitted determination of substitutional atomic
      diffusivities several orders of magnitude smaller than previously possible and
      has also led to the determination of low-temperature equilibrium phase diagrams
      through the measurement of local interface compositions. Elemental segregation to
      grain boundaries is responsible for such deleterious behavior as temper
      embrittlement, stress-corrosion cracking, and other forms of intergranular
      failure. On the other hand, segregation can bring about improvement in behavior:
      sintering aids in ceramics and de-embrittlement of intermetallics. EDS in the AEM
      has been responsible for quantitative analysis of all aspects of the segregation
      process and, more recently, in combination with electron energy-loss spectrometry
      (EELS) has given insight into why boundary segregation results in such
      significant macroscopic changes in properties.

PMID- 10087280
TI  - Low-Voltage Energy-Dispersive X-ray Microanalysis of Bulk Biological Materials.
AB  - : Low-voltage energy-dispersive X-ray microanalysis has a number of distinct
      advantages for measuring the concentration of light elements (Z = 11-20) in a
      largely organic matrix. Between 10 and 4 kV, there is a 50-fold decrease in the
      size of the incident beam-specimen interaction volume which enables discrete
      subcellular compartments to be analyzed. Experiments with mineral and organic
      samples of known chemical composition show that two of the most widely used
      analytical algorithms are capable of providing quantitative data at accelerating
      voltages as low as 5 kV. This technique is used at 5 kV to analyze frozen
      hydrated fracture faces of leaves of the tea plant which are known to contain
      aluminium. Higher levels of aluminium are found in the cell walls and are
      associated with increased levels of silicon and magnesium. The advantages and
      disadvantages of the experimental approach are discussed in relation to analysis
      carried out at higher voltages.

PMID- 10087281
TI  - Standardless Quantitative Electron-Excited X-ray Microanalysis by Energy
      Dispersive Spectrometry: What Is Its Proper Role?
AB  - : Electron beam X-ray microanalysis with semiconductor energy-dispersive
      spectrometry (EDS) performed with standards and calculated matrix corrections can
      yield quantitative results with a distribution such that 95% of analyses fall
      within +/-5% relative for major and minor constituents. Standardless methods
      substitute calculations for the standard intensities, based either on physical
      models of X-ray generation and propagation (first principles) or on mathematical
      fits to remotely measured standards (fitted standards). Error distributions have
      been measured for three different standardless analysis procedures with a suite
      of microanalysis standards including metal alloys, glasses, minerals, ceramics,
      and stoichiometric compounds. For the first-principles standardless procedure,
      the error distribution placed 95% of analyses within +/-50% relative, whereas for
      two commercial fitted standards procedures, the error distributions placed 95% of
      analyses within +/-25% relative. The implication of these error distributions for
      the accuracy of analytical results is considered, and recommendations for the use
      of standardless analysis are given.

PMID- 10087282
TI  - Statistical Considerations in Microanalysis by Energy-Dispersive Spectrometry.
AB  - : X-ray counting statistics plays a key role in establishing confidence limits in
      composition determination by X-ray microanalysis. The process starts with
      measurements of intensity on one or more samples and standards as well as related
      background determinations. Since each individual measurement is subject to
      variability associated with counting statistics, it is necessary to combine all
      of the counting variability according to established mathematical procedures. The
      next step is to apply propagation of error calculations to equations for
      quantitative analysis and determine confidence limits in reported composition.
      Similar concepts can also be applied to trace element determination. This
      approach can then be combined with spectral simulation modeling, making it
      possible to predict detectability limits without additional measurements.

PMID- 10087283
TI  - Measuring Performance of Energy-Dispersive X-ray Systems.
AB  - : As Si(Li) detector technology has matured, many of the fundamental problems
      have been addressed in the competition among manufacturers and there is now an
      expectation, implied by many textbooks, that all energy-dispersive X-ray (EDX)
      detectors are made and will perform in the same way. Although there has been some
      convergence in Si(Li) systems and these are still the most common, manufacturing
      recipes still differ and there are many alternative EDX devices, such as
      microcalorimeters and room temperature detectors, that have both advantages and
      disadvantages over Si(Li). Rather than emphasizing differences in technologies,
      performance measures should reveal benefits relevant to the intended application.
      The instrument is inevitably going to be a "black box" of integrated components;
      this article reviews some of the methods that have been applied and introduces
      some new techniques that can be used to assess performance without resorting to
      complex software or sophisticated mathematical algorithms. Sensitivity,
      resolution, artefacts, and stability are discussed with particular application to
      compositional analysis using electron beam excitation of X-rays in the 100-eV to
      10-keV energy region.

PMID- 10087284
TI  - Superconducting Tunnel Junction Array Development for High-Resolution Energy
      Dispersive X-ray Spectroscopy.
AB  - : Cryogenic energy-dispersive X-ray detectors are being developed because of
      their superior energy resolution (10 eV FWHM for keV X-rays) compared to that
      achieved in semiconductor energy-dispersive spectrometry (EDS) systems. So far,
      their range of application is limited because of their comparably small size and
      low count rate. We present data on the development of superconducting tunnel
      junction (STJ) detector arrays to address both of these issues. A single STJ
      detector has a resolution of around 10 eV below 1 keV and can be operated at
      count rates of the order 10,000 counts/sec. We show that the simultaneous
      operation of several STJ detectors does not dimish their energy resolution
      significantly, and it increases the detector area and the maximum count rate by a
      factor given by the total number of independent channels.

PMID- 10087285
TI  - High-Resolution X-ray Spectroscopy Close to Room Temperature.
AB  - : Originally designed as position-sensitive detectors for particle tracking,
      silicon drift detectors (SDDs) are now used for high-count rate X-ray
      spectroscopy, operating close to room temperature. Their low-capacitance read
      node concept places them among the fastest high-resolution detector systems. They
      have been used in a new spectrum of experiments in the wide field of X-ray
      spectroscopy: fluorescent analysis, diffractometry, materials analysis, and
      synchrotron experiments such as X-ray holography and element imaging in scanning
      electron microscopes. The fact that the detector system can be used at room
      temperature with good spectroscopic performance and at -10 degrees C with
      excellent energy resolution, avoiding liquid nitrogen for cooling and high
      quality vacuum, guarantees a large variety of new applications, independent of
      the laboratory environment. A brief description of the device principles is
      followed by basics on low noise amplification. The performance results of a
      complete detector system are presented as well as some dedicated applications
      already realized, including use in a surface mapping instrument and use of a
      "mini-spectrometer" for the analysis of works of art. Fully depleted pn-charge
      coupled devices (pn-CCDs) have been fabricated for the European X-ray Multi
      Mirror mission (XMM) and the German X-ray satellite ABRIXAS, enabling high-speed,
      low-noise, position-resolving X-ray spectroscopy. The detector was designed and
      fabricated with a homogeneously sensitive area of 36 cm2. At -70 degrees C it has
      a noise of 4 e- rms, with a readout time of the total focal plane array of 4
      msec. The maximum count rate for single photon counting was 10(5) cps under flat
      field conditions. In the integration mode, more than 10(9) cps can be detected at
      6 keV. Its position resolution is on the order of 100 um. The quantum efficiency
      is higher than 90%, ranging from carbon K X-rays (277 eV) up to 10 keV.

PMID- 10087287
TI  - News and Commentary.

PMID- 10087286
TI  - Application of X-ray Optics to Energy-Dispersive Spectroscopy.
AB  - : X-ray optics have been used in X-ray analytical instruments for several years.
      Applications of X-ray optics have been reported in X-ray diffraction, X-ray
      fluorescence, and wavelength dispersive spectroscopy. X-ray optics have been used
      to increase the X-ray flux incident on the sample or to direct and focus emitted
      X-rays from a sample. We report here the use of a grazing incidence optic (GIO)
      as a flux-enhancing collimator for use with an energy-dispersive (ED) detector
      used to perform electron beam microanalysis. We found that the GIO in combination
      with an ED spectrometer (EDS) provides substantial intensity gain for X-ray lines
      with energy below 1 keV. The GIO is also found to provide a modest focus effect,
      and introduces minimal spectral artifacts.

PMID- 10087288
TI  - Overview of QTL mapping software and introduction to map manager QT.
AB  - At least ten software packages are available for marker-based detection and
      localization of loci contributing to quantitative traits in experimental animals
      and plants. Many of these have unique strengths or situations in which they are
      particularly useful. Six were developed by or in collaboration with plant
      geneticists and may not be well known to mammalian geneticists. These software
      packages are reviewed here and compared with a previously undescribed program,
      Map Manager QT, a Mac OS microcomputer program for mapping quantitative trait
      loci in populations derived from backcrosses, intercrosses, and recombinant
      inbred lines. Map Manager QT is an enhanced version of Map Manager Classic (Map
      Manager v2.6.5, Manly 1993), designed for mapping Mendelian loci. This review
      describes the methods Map Manager QT uses for mapping quantitative trait loci and
      describes other features that differ from those in Map Manager Classic. A
      complete description of both Map Manager Classic and Map Manager QT is available
      in the user manual, the on-line version of which can be found at
      http://mcbio.med.buffalo.edu/MMM/MMM.ht ml.

PMID- 10087289
TI  - Genotyping new BXD recombinant inbred mouse strains and comparison of BXD and
      consensus maps.
AB  - Nine additional BXD recombinant inbred (RI) strains have been developed from the
      F2 cross of C57BL/6J and DBA/2J mouse strains. A tenth line stopped breeding in
      the F12 generation. F20 generation breeding pairs from the nine surviving strains
      and an F12 pair from the extinct line were genotyped at 319 genetic markers
      (primarily microsatellites) spanning most of the genome. Where typing data were
      lacking, the established set of 26 BXD strains also were genotyped at these same
      loci. The availability of these additional nine strains enhances the value of the
      BXD RI set for analysis of complex phenotypic traits. The proportion of loci
      still segregating at the F20 generation was found to closely approximate
      expectation, suggesting that selection favoring the retention of heterozygosity
      is not a strong factor. However, the number of crossovers between adjacent
      markers was frequently less than predicted from consensus map distances. A
      significant deficiency of recombinants was observed on Chrs 3, 4, 14, and X. On
      Chr 14, the estimated cumulative BXD map distance between the most proximal and
      distal markers was only 30.2 cM, compared with a distance of 60.0 cM in the
      consensus map. On the X Chr, the estimated and predicted cumulative distances
      were 38.8 and 69.5 cM, respectively. Over all chromosomes, the BXD RI map is
      14.5% shorter than predicted from the consensus map. It is suggested that
      distances in some of the consensus maps are inflated. Alternatively, recombinant
      genotypes could be selected against during inbreeding owing to allelic
      interactions affecting fitness. The latter interpretation implies that relatively
      strong intrachromosomal epistasis is common.

PMID- 10087290
TI  - LAMS(TM)--a laboratory animal management system.
AB  - The LAMStrade mark database stores data on a colony of breeding animals. Forms
      are hierarchial and show details of internal codes, matings, litters, and
      offspring. The identifier given to each animal can be subdivided as such. Each
      form shows an abbreviated list of the related data from the form one level down,
      and some special fields, when double-clicked, cause the related record to be
      displayed. The print button allows the user to print the current record and its
      related records. Other buttons on each form allow the user to amend, delete,
      find, and add records within certain rules. User-defined lists are created to
      allow the selection of various characteristics during data entry. The offspring
      form contains a section where the user can define the label of a comment and/or a
      text field. This name is then always subsequently available as an option in a
      list of user-defined labels. Reports are available for tailtipping dates (if
      applicable) and calculation of genetic ratios. A queryform allows the user to
      filter the records in the offspring form to the criteria specified, and a display
      of the actual query submitted is shown. An integrated HELP is available. The
      LAMStrade mark database is available at http://www.hgu.mrc.ac.uk/Softdata/Lams

PMID- 10087291
TI  - Spontaneously hyperlipidemic (SHL) mice: Japanese wild mice with apolipoprotein E
      deficiency.
AB  - During inbreeding of Japanese wild mice (Mus musculus molossinus), we established
      a strain of mice with severe cutaneous xanthomatous lesions. Since those mice
      showed high plasma cholesterol values, we named them spontaneously hyperlipidemic
      (SHL) mice; total cholesterol values of these mice (even when fed on conventional
      low-fat diet) are unusually high throughout the life span. The xanthomatous
      lesions appear in palms and distal extremities of forelimbs as early as 4 weeks
      after birth, and continue to expand to chest, abdomen, and face until the mice
      die before 14 months of age. Histological examination of these lesions revealed
      cholesterol crystal deposits, an infiltration of foam cells or macrophages, while
      that of the vascular system revealed atherosclerosis in the aortic sinus.
      Immunoblot and Northern blot analyses failed to detect apolipoprotein E (APOE)
      expression in these animals. Consistent with these findings, Southern blot
      analysis found disruption of the Apoe gene in SHL mice. Phenotypes of SHL mice,
      however, were distinct from those of Apoetm1Unc (hereafter Apoe-/-) mice, whose
      Apoe gene was disrupted by homologous recombination; hypercholesterolemia and
      xanthoma were more severe in SHL mice than in Apoe-/- mice, while atherosclerosis
      was milder in SHL mice. These distinctions suggest that there are modifier genes
      for the phenotypes. Alternatively, other gene(s), besides the Apoe gene, may be
      mutated in SHL mice. In either case, comparative genetic and molecular dissection
      of SHL mice will provide a good opportunity to understand the genetic basis for
      hyperlipidemia and atherosclerosis.

PMID- 10087292
TI  - RasGRP, a Ras activator: mouse and human cDNA sequences and chromosomal
      positions.
AB  - We recently reported the molecular cloning of a novel transforming rat brain
      cDNA, rbc7, that encodes a Ras activator (Ebinu et al. Science 280, p. 1082,
      1998). We proposed that this cDNA is a 5' and 3' truncated version of a larger
      normal transcript that encodes a predicted 90-kDa protein which we called RasGRP
      (Ras guanyl nucleotide releasing protein). We have now studied the structure of
      the mouse and human sequences and confirmed our conclusions about the nature of
      the 5' truncation. The human gene has been localized to 15q15 by an in situ
      hybridization technique, while the mouse gene has been positioned on Chr 2 near
      thrombospondin by linkage analysis. The relatedness of RasGRP to another human
      sequence and a hypothetical nematode protein are also discussed.

PMID- 10087293
TI  - Identification of a novel inflammation-protective locus in the Fischer rat.
AB  - Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N
      rats are relatively resistant to development of a wide variety of inflammatory
      diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs.
      F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10
      that protects in a dominant fashion against the exudate volume component of
      innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near
      the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be
      similar to one of the multiple regions found to link to inflammatory arthritis
      phenotypes in other crosses. The suggestive linkage on Chr 2 has not been
      previously reported and does not seem to contribute to this phenotype in the same
      manner as the QTL on Chr 10. These findings are consistent with the hypothesis
      that the innate exudate volume trait is a sub-phenotype of more complex
      inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage
      region could account for differences in this non-specific acute phase component
      of the inflammatory response. Since the rat Chr 10 exudate volume linkage region
      we have identified is syntenic with a region of human Chr 17 that has been shown
      to link to a variety of autoimmune/inflammatory diseases, including insulin
      dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of
      genes within this linkage region will shed light on genes relevant to the
      earliest inflammatory component and to susceptibility and resistance to such
      human autoimmune/inflammatory diseases.

PMID- 10087294
TI  - Rat osteotesticular phosphatase gene (Esp): genomic structure and chromosome
      location.
AB  - Osteotesticular phosphatase (OST-PTPase) is a class III receptor-type tyrosine
      phosphatase (RPTPase). It has 10 tandem fibronectin III-like (FN-III) repeats in
      the extracellular region and two phosphatase domains in the intracellular region.
      The expression of the rat OST-PTPase gene, Esp, is restricted to osteoblasts and
      Sertoli cells, and the transcript level in osteoblasts is highly up-regulated by
      parathyroid hormone and cAMP treatment. We report here the cloning and
      characterization of the rat Esp gene, including a 2.9-kb 5' flanking region
      sequence. Two potential binding sites for Osf2/Cbfa1, an osteoblast-specific
      transcription factor, are present in the promoter. Esp is composed of 35 exons,
      but spans merely 20 kb, making it the most compact RPTPase gene identified. Each
      FN-III repeat is encoded by a single exon flanked with phase 1 introns. Two
      phosphatase domains are encoded by 16 exons in a genomic organization similar to
      those in RPRPalpha, RPTPgamma, and Ptprc genes. Esp was mapped by fluorescence in
      situ hybridization to rat chromosome 13q1. These results represent the first
      genomic structure of a mammalian class III RPTPase gene.

PMID- 10087295
TI  - Chromosomal localization of acidic and basic keratin genes of the domestic dog.
AB  - Our laboratories are interested in characterizing genes involved in the myriad of
      heritable diseases affecting the domestic dog, Canis lupus familiaris, and in
      development of detailed genetic and physical maps of the canine genome. Included
      in these efforts is examination of conservation of the genetic organization,
      structure, and function of gene families involved in diseases of the canine skin,
      skeleton, and eye. To that end, study of the highly conserved keratin gene family
      was undertaken. Keratins belong to the superfamily of intermediate filaments and
      are the major structural proteins of the epidermis, hair, and nail. The keratins
      are highly conserved throughout vertebrate evolution both at the DNA and amino
      acid sequence levels. Mutations in genes encoding epithelial keratins are known
      to cause various diseases in humans, and similar histopathological presentations
      have been reported in the dog. The keratins are divided into two groups, type I
      (acidic) and type II (basic). In the human, the genes encoding the acidic and
      basic keratins are clustered on Chrs 17 and 12, respectively. The same genetic
      arrangement is seen in the mouse with the acidic and basic keratin gene clusters
      found on Chrs 11 and 15, respectively. Reported here are the chromosomal
      localization of acidic and basic canine keratin genes as well as supportive
      sequence data. Fluorescence in situ hybridization (FISH) experiments with clones
      isolated from a canine genomic library suggest that the acidic keratin gene
      cluster resides on CFA9 and the basic keratin gene cluster is located on CFA27.

PMID- 10087296
TI  - Characterization and chromosomal localization of the human insulin-like growth
      factor-binding protein 6 gene.
AB  - Insulin-like growth factor-binding protein 6 (IGFBP6), an extracellular protein
      with preferential affinity for insulin-like growth factor (IGF) II, belongs to a
      family of binding proteins with at least six members. We have characterized the
      genomic structure and the chromosomal location of the human IGFBP6, which is
      present in the human genome as a single-copy gene spanning 4.7 kb. It consists of
      four exons, encoding the translated regions, with sizes of 334, 146, 120, and 123
      bp, while the intervening introns are 2661, 182, and 844 bp. Three mRNA cap sites
      were localized 101, 100, and 96 bp upstream of the ATG translation start codon as
      determined by S1 nuclease analysis. The proximal 5'-flanking region does not have
      any TATA or CAAT consensus sequences. The IGFBP6 was localized to Chr 12 by
      analysis of somatic cell hybrids and regionalized to 12q13 by fluorescence DNA in
      situ hybridization.

PMID- 10087297
TI  - Embryonic stem cells can be used to construct hybrid cell lines containing a
      single, selectable murine chromosome.
AB  - Microcell-mediated chromosome transfer is a useful technique for the study of
      gene function, gene regulation, gene mapping, and functional cloning in mammalian
      cells. Complete panels of donor cell lines, each containing a different human
      chromosome, have been developed. These donor cell lines contain a single human
      chromosome marked with a dominant selectable gene in a rodent cell background.
      However, a similar panel does not exist for murine chromosomes. To produce mouse
      monochromosomal donor hybrids, we have utilized embryonic stem (ES) cells with
      targeted gene disruptions of known chromosomal location as starting material. ES
      cells with mutations in aprt, fyn, and myc were utilized to generate
      monochromosomal hybrids with neomycin phosphotransferase-marked murine Chr 8, 10,
      or 15 respectively in a hamster or rat background. This same methodology can be
      used to generate a complete panel of marked mouse chromosomes for somatic cell
      genetic experimentaion.

PMID- 10087298
TI  - Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia.
AB  - Mutations in the PHEX gene (phosphate-regulating gene with homology to
      endopeptidases on the X-chromosome) are responsible for X-linked hypophosphatemia
      (HYP). We previously reported the full-length coding sequence of murine Phex cDNA
      and provided evidence of Phex expression in bone and tooth. Here, we report the
      cloning of the entire 3.5-kb 3'UTR of the Phex gene, yielding a total of 6248 bp
      for the Phex transcript. Southern blot and RT-PCR analyses revealed that the 3'
      end of the coding sequence and the 3'UTR of the Phex gene, spanning exons 16 to
      22, are deleted in Hyp, the mouse model for HYP. Northern blot analysis of bone
      revealed lack of expression of stable Phex mRNA from the mutant allele and
      expression of Phex transcripts from the wild-type allele in Hyp heterozygous
      females. Expression of the Phex protein in heterozygotes was confirmed by Western
      analysis with antibodies raised against a COOH-terminal peptide of the mouse Phex
      protein. Taken together, these results indicate that the dominant pattern of Hyp
      inheritance in mice is due to Phex haploinsufficiency.

PMID- 10087299
TI  - Exon structure of the nuclear factor I DNA-binding domain from C. elegans to
      mammals.
AB  - The Nuclear Factor I (NFI) family of DNA-binding proteins is essential for
      adenovirus DNA replication and the transcription of many cellular genes. Mammals
      have four genes encoding NFI proteins, C. elegans has only a single NFI gene, and
      prokaryotes have none. To assess the relationship between members of this
      unusually small family of transcription/replication factors, we mapped the
      chromosomal locations of the four murine NFI genes and analyzed the exons
      encoding the DNA-binding domains of the mouse, Amphioxus, and C. elegans NFI
      genes. The four murine NFI genes are on Chrs 4 (Nfia and Nfib), 8 (Nfix), and 10
      (Nfic), suggesting early duplication of the genes and dispersal throughout the
      genome. The DNA-binding domains of all four NFI genes are encoded by large (532
      bp) exons with identical splice acceptor and donor sites in each. In contrast,
      the C. elegans nfi-1 gene has four phased introns interrupting this DNA-binding,
      domain-encoding exon, and the last exon extends 213 bp past the splice site used
      in all four murine genes. In addition, the introns present in C. elegans nfi-1
      are missing from the NFI genes of Amphioxus and all mammalian genomes examined.
      This analysis of the exon structure of the C. elegans and murine NFI genes
      indicates that the murine genes were probably generated by duplication of a C.
      elegans-like ancestral gene, but that significant changes have occurred in the
      genomic organization of either the C. elegans or murine NFI genes during
      evolution.

PMID- 10087300
TI  - Chromosomal localization of the Huntingtin associated protein (HAP-1) gene in
      mouse and humans with radiation hybrid and interspecific backcross mapping.

PMID- 10087301
TI  - Identification of genes within the Krd deletion on mouse chromosome 19.

PMID- 10087302
TI  - Genetic mapping of eight SH3 domain genes on seven mouse chromosomes.

PMID- 10087303
TI  - Linkage and physical mapping of rat microsatellites derived from minisatellite
      loci.

PMID- 10087304
TI  - Determination of the genomic organization of human presenilin 1 by fiber-FISH
      analysis and restriction mapping of cloned DNA.

PMID- 10087305
TI  - Cloning, expression, and promoter structure of a mammalian inner centromere
      protein (INCENP).

PMID- 10087306
TI  - Regulation and expression of the murine PMP22 gene.

PMID- 10087307
TI  - Alternative splicing of hMSH4: two isoforms in testis and abnormal transcripts in
      somatic tissues.

PMID- 10087309
TI  - Kaposi's sarcoma: breeding ground of herpesviridae - A tour de force over viral
      evolution (review).
AB  - After reviewing the molecular biological basis of prominent theories for the
      integration of viruses into the earliest forms of living matter, an account is
      given on the immunoevasive strategies viruses have had to acquire in order to
      secure their existence against the most sophisticated anti-viral defensive
      mechanisms evolving in their hosts. Herpes-viridae and Kaposi's sarcoma
      illustrate the complexity of host-virus relationship. In following the
      evolutionary steps of simians and hominoids to Homo, it becomes evident that: a)
      Epstein-Barr virus evolved in Africa and its ancestral viruses are present in
      cercopithecines and hominoids; b) human herpes-virus-8-related viruses are
      present in macaques, in S. American primates and in Homo but such isolates from
      the great apes are missing. Thus interspecies transfer occurred from lower
      monkeys to Homo but when and at what geographical location? The human
      retrolentiviruses also jumped species barriers: this occurred recently in Africa,
      from great apes (chimpanzee and bonobo) to Homo sapiens (except when HIV-2 was
      transferred to mankind from sooty mangabeys). The matter is further complicated
      by the long coevolutionary cooperative interactions between herpes- and
      retrolentiviruses. Of pathological entities suspected to be etiologically
      affected by such complex viral cooperation, the origin of Reed-Sternberg cells of
      Hodgkin's disease is singled out for critical analysis. In this article the
      senior author summarizes his own 52 years of studentship in virology.

PMID- 10087310
TI  - Primary intracerebral lymphoma: A clinicopathological study of 28 patients.
AB  - Primary intracerebral lymphoma is an uncommon presenting site for non-Hodgkin's
      lymphoma. The authors review 28 histopathologically confirmed, consecutive cases,
      presenting over a 15-year period. The cohort included 20 males and 8 females with
      a mean age at diagnosis of 54 years (range 27-75 years). Subtotal resection was
      performed in 8 patients. Radical whole brain irradiation was given to 27
      patients. One patient was too unwell to receive treatment and quickly died. Three
      patients also had chemotherapy. Clinical remission was achieved in 19 patients.
      Of these, 9 relapsed after a median interval of 18 months. Nine patients (32%
      total cohort) are still alive and in remission after a median follow-up of 2
      years and 10 months (range 11 months to 11 years and 5 months). Cause of death
      was intracerebral lymphoma in 13 of the 19 patients who died. Median survival was
      12 months in this group (range 1 week to 4 years and 9 months). Actuarial 5-year
      survival for all patients was 19%. The prognosis for patients with primary
      intracerebral lymphoma treated with radiotherapy alone is poor.

PMID- 10087311
TI  - Subcellular localization of BRCA1 protein in sporadic breast carcinoma with or
      without allelic loss of BRCA1 gene.
AB  - The localization of BRCA1 protein was studied in 49 sporadic breast carcinomas
      for which allelic losses of BRCA1 have been investigated. One group consisted of
      15 breast carcinomas having one allelic loss of BRCA1 and the other group of 34
      breast carcinomas with no allelic loss of BRCA1. The localization of BRCA1 in the
      2 groups was performed using polyclonal antibodies (K-18; C-20; D-20; I-20)
      raised against BRCA1 and by comparing frozen and paraffin-embedded tissues. We
      show that no correlation was found between the expression of BRCA1 protein and
      allelic loss of BRCA1. But, the nuclear detection of BRCA1 in frozen samples was
      improved when compared to paraffinized ones.

PMID- 10087312
TI  - HER-2/neu gene amplification by fluorescence in situ hybridization allows risk
      group assessment in node-negative breast cancer.
AB  - In a collective of 112 node-negative breast cancer patients, we compared the
      prognostic impact of HER-2/neu gene amplification (AMP) determined by
      fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression
      (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors
      (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor
      invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI
      1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still
      alive at time of analysis was 7 years. Automated FISH and IHC were performed on
      parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was
      detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the
      cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results
      were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu
      AMP significantly predicted both disease-free (DFS) and overall survival (OS).
      HER-2/neu EXP was significant for OS, only. In multivariate analysis of all
      analyzed prognostic factors, HER-2/neu AMP was the only independent predictive
      factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together
      with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7
      year median follow-up: patients with low levels of both uPA and PAI-1 and no HER
      2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining
      patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a
      more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC.
      Combining the HER-2/neu gene status measured by FISH with levels of tumor
      invasion markers uPA and PAI-1 improves clinically relevant risk-group
      assessment. In addition to its prognostic strength, the significant impact of HER
      2/neu AMP on OS may reflect its ability to predict resistance to systemic
      therapy.

PMID- 10087313
TI  - Effects of granisetron in children undergoing high-dose chemotherapy: a multi
      institutional, cross-over study.
AB  - The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were
      compared using a cross-over method to determine the optimal dose in children with
      solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset
      of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of
      granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20
      microg/kg group. The average frequency of vomiting was 7.22 times in the 20
      microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems
      were associated with either dose. The 40 microg/kg dose of granisetron appears to
      be more optimal.

PMID- 10087314
TI  - Analysis of antibodies to p16INK4A tumor suppressor gene products in lung cancer
      patients.
AB  - We examined by immunoblotting antibodies that bind to p16INK4A tumor suppressor
      gene products in the sera of patients with lung cancer. Sera from 15 to 102
      patients, including 6 with adenocarcinoma, 3 with squamous cell carcinoma, 2 with
      large cell carcinoma and 4 with small cell carcinoma, reacted with a glutathione
      S-transferase (GST) fusion protein containing whole human anti-p16INK4A, produced
      by Escherichia coli. However, sera from 30 normal volunteers did not react with
      the GST-p16INK4A fusion protein. The background such as age, gender, performance
      status, histology, stage, smoking history, and prior treatment was not
      significantly different between the patients with and without anti-GST-p16INK4A
      antibodies. Circulating p16INK4A tumor suppressor products were not detected in
      any individuals with lung cancer or in the normal controls.

PMID- 10087315
TI  - Apoptotic cell death of human gastric tumor induced by nucleosides from CD57+HLA
      DRbright natural suppressor cell line.
AB  - CD57+HLA-DRbright natural suppressor (57.DR-NS) cell line derived from human
      decidual tissue generated apoptosis in a human gastric carcinoma cell line (GCIY)
      but not in a human diploid normal cell line (WI-38). The factors released from
      57.DR-NS cells were purified by thin-layer-chromatography (TLC) and separated by
      high performance liquid chromatography (HPLC) into six components. The
      physicochemical structures of the six components were determined as a series of
      nucleosides and their modified forms collectively termed <apoptosis inducing
      nucleosides (AINs)> in a previous study. They could generate apoptotic cell death
      of GCIY malignant target cells, but not disturb the viability of WI-38 normal
      target cells. The administration of AINs into GCIY tumor bearing SCID mice
      resulted in drastic suppression of tumor growth followed by the decrease in tumor
      size due to the occurrence of apoptosis in tumor tissues.

PMID- 10087316
TI  - Bone marrow-derived dendritic cells incorporate and process hydrophobized
      polysaccharide/oncoprotein complex as antigen presenting cells.
AB  - We have previously shown that a novel hydrophobized polysaccharide/oncoprotein
      complex vaccine can induce immune responses against the HER2/neu/c-erbB2 (HER2)
      expressing tumors. Bone marrow-derived dendritic cells (DCs), as antigen
      presenting cells (APCs), are the first candidates for presentation of tumor
      antigens. The aim of this study was to see whether DCs are able to elicit antigen
      specific host immune responses by stimulating the proliferation of T cells after
      exposure to cholesteryl group bearing pullulan (CHP) and HER2 protein complex.
      Vaccination by CHP-HER2 complex was as effective as cholesteryl group bearing
      mannan (CHM) and HER2 complex on which we reported previously. Immunization of
      mice with HER2 expressing CMS17HE tumor cells generated both CD4+ T cells and
      CD8+ T cells reactive with CHP-HER2 complex pretreated DCs. In addition,
      immunization with either CHP-HER2 complex or HER2 protein alone could also
      generate both CD4+ T cells and CD8+ T cells specifically reactive with CHP-HER2
      complex pretreated DCs. The complete rejection of tumors occurred when
      immunization with CHP-HER2 complex pretreated DCs was started 10 days after tumor
      inoculation. Therefore, bone marrow-derived DCs pretreated with hydrophobized
      polysaccharide/oncoprotein complex are a powerful tool for enhancing the
      effectiveness of oncoprotein for anti-tumor vaccination, opening new options for
      immune cell therapy.

PMID- 10087317
TI  - HUB1 is an autoantigen frequently eliciting humoral immune response in patients
      with adult T cell leukemia.
AB  - The immunological screening of a cDNA phage expression library prepared from an
      adult T cell leukemia (ATL) cell line, ST1, was performed with IgG class
      antibodies in the serum of an ATL patient by the SEREX method to analyze the
      repertoire of antigen molecules in ATL. Ten different cDNAs, 7 previously
      reported and 3 newly identified, were isolated. One of the identified cDNAs was
      homologous to the recently reported gene, HTLV-I U5RE binding protein 1 (HUB1)
      encoding a protein binding to a possible repressor element of the long terminal
      repeat of the human T lymphotropic virus type I (HTLV-I). The obtained cDNA was
      expressed as a fusion protein with glutathione S-transferase. HUB1 protein was
      prepared by subsequent treatment of the fusion protein with thrombin. Reactivity
      of IgG serum samples from ATL patients, asymptomatic HTLV-I carriers and normal
      donors against the purified protein was examined by Western blot analysis. Twenty
      one out of 30 samples (70.0%) from ATL patients, 10/24 samples (41.7%) from HTLV
      I carriers and 9/24 samples (37.5%) from healthy donors showed positive
      reactivity, indicating the autoantigenicity of HUB1. The development of ATL may
      be related to higher production of antibodies against HUB1.

PMID- 10087318
TI  - Improvement in detecting telomerase activity using silica-based resin treatment:
      An experience of urine in bladder carcinoma.
AB  - To improve the telomeric repeat amplification protocol (TRAP) assay to detect
      telomerase activity using a small amount of sample, we used a resin-column to
      purify and to concentrate the TS extension DNA sequence. We used 14 samples of
      naturally voided urine (10 ml) from patients with bladder carcinoma and 9 urine
      samples from patients with non-malignant urological neoplasias. We used
      ethylenediamine tetraacetic acid (EDTA) to stabilize telomerase activity and
      resin treatment to concentrate TS-extended DNA and to exclude PCR inhibitor(s),
      and then performed extract-based fluorescence TRAP to detect telomerase activity.
      None of the urinary samples without resin-column treatment had detectable
      telomerase activity, whereas, in resin-column treated samples, 4/9 (44%) urine
      samples without EDTA and 9/14 (64%) with EDTA treatment had detectable telomerase
      activity. A combination of EDTA treatment and resin-column thus may be available
      to detect telomerase activity using a relatively small amount of secretion
      fluids, including exfoliated urinary cells.

PMID- 10087319
TI  - Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer.
AB  - Prostate cancer is the most common cancer amongst males in developed countries.
      Surgical removal of the prostate effectively cures the primary disease but the
      metastatic disease is refractory to most forms of chemotherapy. There is a
      clinical need to develop novel treatment strategies that exploit the mode of
      action of both conventional and alternative drugs/medicinal plants. We have been
      investigating the anti-proliferative and anti-tumor effects of an herbal
      preparation termed PC-SPES (patent pending, US serial number 08/697, 920) which
      is a refined powder of eight different medicinal plants. PC-SPES administered as
      a food supplement caused a dramatic decrease in prostate specific antigen levels
      in some prostate cancer patients with advanced disease. These preliminary
      clinical findings laid the foundation for a program to examine the in vitro and
      in vivo effects of PC-SPES, and identify the active component in this mixture so
      that a standardized treatment regimen can be formulated. In this communication,
      we report the anti-tumor effects of PC-SPES incorporated in the diet utilizing a
      well studied Dunning R3327 rat prostate cancer model. Dietary PC-SPES at levels
      of 0.05% and 0.025% did not exhibit any toxicity and no significant difference in
      food intake was noted at the end of six weeks. Dose dependent inhibitory effect
      of dietary PC-SPES was observed on both tumor incidence (P=0. 01) and rate of
      tumor growth when tumors were induced in syngeneic Copenhagen rats by intradermal
      injections of MAT-LyLu cells that are known to metastasize in the lung and lymph
      nodes. The number of pulmonary metastases in animals on PC-SPES that showed no
      primary tumor growth had no metastatic lesions in the lung, however, in animals
      that did not respond to PC-SPES, the number of pulmonary metastases was not
      significantly different from the non-treated controls. The significant anti-tumor
      effects of PC-SPES on MAT-LyLu induced tumorigenesis and metastasis in Copenhagen
      rats, in general refractory to most conventional therapy, suggests a therapeutic
      benefit of this herbal food supplement and may be a useful adjuvant to
      conventional therapeutic modalities.

PMID- 10087320
TI  - No microsatellite instability, but frequent LOH in liposarcomas.
AB  - To evaluate the significance of microsatellite instability (MI) and loss of
      heterozygosity (LOH) in the development of different histological subgroups of
      liposarcomas, we examined 28 tissue-samples from 21 patients and the
      corresponding non-neoplastic reference tissues. We investigated nine
      microsatellite loci and detected no MI. LOH for at least one marker was observed
      in 11 of 28 tumours (39%). Widespread allelic losses were a common characteristic
      of pleomorphic liposarcomas. Well-differentiated variants did not show LOH
      (p<0.003). Our findings support the idea that liposarcoma subgroups are defined
      by different spectra of genetic alterations. Inefficient DNA mismatch repair does
      not seem to be involved in the oncogenesis of liposarcomas.

PMID- 10087321
TI  - Levels of telomerase catalytic subunit mRNA as a predictor of potential
      malignancy.
AB  - This study investigated the relationship between the levels of human telomerase
      reverse transcriptase (hTERT) mRNA and that of telomerase activity in
      hepatocellular carcinoma (HCC). A significant correlation between hTERT mRNA
      expression and telomerase activity by transfecting the gene encoding hTERT into
      telomerase-negative human fibroblast cells has clearly been demonstrated.
      However, the relationship between levels of telomerase activity and that of hTERT
      mRNA has yet to be elucidated. In this study, the levels of hTERT mRNA were
      analyzed in 24 HCC patients by real-time PCR. And the intensity of telomerase
      activity was analyzed by fluorescence-based TRAP method. The difference of hTERT
      mRNA level was highly significant between tumor tissues and non-cancerous liver
      tissues. And there were significant correlations between the levels of hTERT mRNA
      and that of telomerase activity (r=0.751) in tumor tissues. We observed a strong
      correlation between levels of hTERT mRNA and that of telomerase activity in HCC.
      Our results suggest that the levels of hTERT mRNA would be useful in genetic
      diagnostic tests, instead of telomerase activity, to screen at-risk patients of
      HCC in human liver tissues.

PMID- 10087322
TI  - Hyaluronan activates mitogen-activated protein kinase via Ras-signaling pathway.
AB  - Hyaluronan (HA) triggers a wide variety of cellular functions, yet its signaling
      pathway remains largely unclear. We found that HA-treatment of 3Y1 cells
      activated tyrosine phosphorylation of cellular proteins and mitogen-activated
      protein (MAP) kinase in a time- and dose-dependent manner, and, subsequently,
      stimulated cell growth. This HA-activity was resistant to boiling at 100 degrees
      C but completely abolished by treatment with hyaluronidase, suggesting that HA
      itself, but not any HA-associated proteins, has the activity. In addition, we
      found that HA-dependent activation of MAP kinase was strongly suppressed by the
      expression of dominant negative ras (S17N ras). These results suggest that Ras
      MAP kinase pathway is activated by HA and may play an important role in HA
      dependent signaling.

PMID- 10087323
TI  - Growth inhibition by dehydrothyrsiferol - a non-Pgp modulator, derived from a
      marine red alga - in human breast cancer cell lines.
AB  - The novel marine terpenoid dehydrothyrsiferol (DHT) has been isolated from a
      Canarian red alga Laurencia viridis sp. nov (Ceramiales, Rhodomelaceae) (1). Its
      cytotoxicity against three human breast cancer cell lines, namely T47D, ZR-75-1,
      and Hs578T was examined and compared with the chemotherapeutic compound
      doxorubicin and the mitosis-inhibitor colchicine. Primary breast carcinomas
      exhibit MDR1 gene expression (3). As the investigated mammary cell lines did not
      exhibit rhodamine 123 efflux we proved in a P-glycoprotein (Pgp) overexpressing
      human epidermoid cancer cell line that the marine metabolite does not modulate
      Pgp mediated drug transport. Therefore, it could be used in Pgp expressing cancer
      cells without interference.

PMID- 10087324
TI  - Acyclic nucleotide analogues suppress growth and induce apoptosis in human
      leukemia cell lines.
AB  - Acyclic nucleotide analogues perturb DNA replication by terminating the growing
      DNA chain. The analogues selected for testing on human leukemia cell lines,
      namely 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), 9-[2-(phosphonomethoxy)ethyl]
      2,6-diaminopurine (PMEDAP), and 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG)
      exhibited growth-inhibiting activity at low concentrations, and apoptosis
      inducing activity at high concentrations. A common feature was a reduction of the
      proportion of G1 cell cycle phase. Activities of the analogues increased in the
      order PMEA<PMEDAP<PMEG. The lymphoid cell line MOLT-4 was more susceptible to the
      agents than the myelogenous cell lines HL-60 and ML-1. In semicontinuous cultures
      in the presence of low-concentration PMEG the steady-state viable cell
      concentration was lower and the proportion of G1 phase cells was suppressed. Upon
      gradual removal of PMEG from the medium, the cell concentration and the DNA
      profile returned to values characteristic for the control culture. It is
      concluded that low concentrations of the analogues cause reversible slowdown of
      growth, due to continuous repairing of damaged DNA, while high-concentrations
      induce apoptosis in irreparably damaged cells.

PMID- 10087325
TI  - Detection of mutation(s) or polymorphic loci in the genome of experimental animal
      and human cancer tissues by RAPD/AP-PCR depend on DNA polymerase.
AB  - Examination of mutations by random amplified polymorphic DNA (RAPD) (also called
      arbitrarily primed PCR = AP-PCR) in the breast and Wilm's human cancer tissues as
      well as in estrogen-induced hamster kidney cancer tissues revealed a gain or loss
      of amplified fragments sizes in breast and Wilm's tumors compared to their
      respective controls. We also observed changes in the intensity of amplified
      fragments in tumor DNA compared to control DNA. Most importantly, we found that
      detection of mutation in the genome of cancer tissue compared to normal tissue by
      RAPD/AP-PCR depends upon the type of DNA polymerases used. This is the first
      report showing that polymerase ability to extend a particular locus of the gene
      is influenced by mutation in the primer binding sites in the competitive
      environment where several genomic sequences flanked to a random primer are co
      amplified by RAPD/AP-PCR. Findings of this study suggest that: i) instead of
      directly adopting published RAPD protocol it is essential to optimize RAPD
      reaction conditions by varying magnesium chloride and polymerase concentration
      with different amounts of DNA templates in order to observe reproducible
      fingerprints of randomly amplified polymorphic DNA fragments, ii) alterations in
      the genome as a loss, gain, or decrease and increase in amplification intensity
      of loci were observed in human tumors as well as in an experimental animal tumor,
      and iii) before concluding that a mutation is not present when using RAPD/AP-PCR,
      different polymerases should be used to amplify the genome of the same control or
      tumor tissues.

PMID- 10087326
TI  - Confluence dependent resistance to photo-activated hypericin in HeLa cells.
AB  - Hypericin is a natural photo-active pigment produced by plants of the genus
      Hypericum. The compound exhibits a potent photocytotoxic activity in vitro and in
      vivo. Using HeLa cells we further investigated whether the photocytotoxic in
      vitro effect of hypericin is influenced by the cell density. It was demonstrated
      that hypericin-induced photocytotoxicity in HeLa cells depends significantly on
      the amount of cells in culture, as low cell density cultures were more responsive
      to photodynamic therapy (PDT) than confluent or hyperconfluent cell cultures.
      This confluence dependent resistance (CDR) can be explained in terms of a
      decrease in hypericin cellular uptake. The phenomenon is not caused by the
      depletion of hypericin from the medium by high-density cell cultures since the
      extra-cellular availability of the drug is not altered by the increase in cell
      density and does not appear to be a limiting factor. Importantly, since confluent
      or hyperconfluent cell cultures can better mimic the high cell density of the
      solid tumour, CDR should be taken into consideration whenever resistance of solid
      tumours to PDT with hypericin is observed.

PMID- 10087327
TI  - Expression and function of Flt3/flk2 in human tumor cell lines.
AB  - The receptor tyrosine kinase Flt3 is expressed on the blasts of a high proportion
      of AML cases. We were interested in the expression and function of Flt3 on
      various human tumors. human tumor cell lines were tested for Flt3 expression by
      northern blot analysis and RT-PCR using head/neck (n=3), breast (n=4), ovarian
      (n=4), small cell lung (n=2), non-small cell lung (n=2), gastric (n=1), colon
      (n=3), pancreatic (n=1) and prostate carcinoma (n=1), choriocarcinoma (n=1),
      glioblastoma (n=5), neuroblastoma (n=1), melanoma (n=3), lymphoma (n=1),
      Hodgkin's disease (n=2), and leukemic (n=6) cell lines. With no expression on the
      other cell samples, 3 of 6 leukemic cell lines showed expression of Flt3 mRNA.
      The cDNA region corresponding to the juxtamembrane domain did not show any
      mutation as determined by sequence analysis. In all 3 positive cell lines,
      protein expression was verified by immunoprecipitation followed by immunoblot
      analysis. Although Flt3 is functional in these cell lines, as judged by ligand
      dependent receptor autophosphorylation, it only mediates a proliferative response
      in 2 of the 3 cell lines. In conclusion, Flt3 is expressed exclusively in
      hematopoietic malignancies. Although early signalling events are detectable in
      all Flt3-positive cell lines tested, the expression of Flt3 does not predict a
      proliferative response of the cell lines. No internal tandem duplication of the
      juxtamembrane domain can be observed.

PMID- 10087328
TI  - Murine dendritic cells transduced with an adenoviral vector expressing a defined
      tumor antigen can overcome anti-adenovirus neutralizing immunity and induce
      effective tumor regression.
AB  - In this study transduced dendritic cells (DCs) were used to enhance
      immunogenecity of a specific tumor antigen. Using a polyoma middle T (PyMT)
      transgenic mammary carcinoma model we found that injections of DCs transduced
      with an adenoviral (Ad) vector expressing PyMT (DCAd-PymT) led to potent specific
      anti-tumor immunity. Efficacy was not affected by neutralizing Abs (high or low
      titers) and naive animals did not produce detectable anti-Ad Abs following two
      injections of transduced DCs. Repeated injections of transduced DCs significantly
      improved therapeutic efficacy in mice with established lung metastases. These
      data emphasize the ability of Ad-infected DCs to: i) minimize anti-Ad Ab
      production, ii) overcome pre-existing anti-Ad humoral immunity, and iii) improve
      vaccination efficacy when injected more than once.

PMID- 10087329
TI  - Notch-1 expression levels in 3T3-L1 cells influence ras signaling and
      transformation by oncogenic ras.
AB  - Notch proteins participate in interactions between several cell types involved on
      the specification of numerous cell fates during development. We previously showed
      that enforced downregulation of Notch-1 expression prevented adipogenesis of 3T3
      L1 cells. Since adipogenesis of 3T3-L1 cells can be induced by oncogenic ras, we
      studied whether this was also the case in 3T3-L1 cells with decreased levels of
      Notch-1 expression. We found that oncogenic ras induces transformation and not
      differentiation of 3T3-L1 cells with diminished levels of Notch-1. This result
      suggests that Notch-1 is implicated in the interpretation of signals leading to
      activation of p21 Ras.

PMID- 10087330
TI  - Prognostic markers in clinically localised prostate cancer.
AB  - The prognostic value of immunohistochemical staining of P53, BCL-2, p27kip1, PSA,
      AR and MIB-1 was compared with that of established prognostic variables (Gleason
      score, surgical margins, tumour volume) following radical prostatectomy. Five
      groups were selected: negative margins with stable serum PSA (n=11), negative
      margins with rising serum PSA (n=7), positive margins with stable serum PSA
      (n=7), positive margins with rising serum PSA (6) and patients with
      micrometastatic disease diagnosed in lymph nodes removed during radical
      prostatectomy (n=8). Gleason score and tumour volume were of prognostic
      significance and immunohistochemical staining for MIB-1 and BCL-2 showed added
      independent prognostic significance in multivariate analysis.

PMID- 10087331
TI  - NO-dependent regulation of lectin- and menadione-induced H2O2 production by cells
      from pleural effusions of lung cancer patients and by immune cells.
AB  - Molecular mechanisms of interplay between reactive oxygen (superoxide, hydroxyl
      radical, H2O2 etc.) and nitrogen (nitric oxide - NO, ONOO-, NO2-, NO3- etc.)
      forms are proposed to be of key importance for cell and tumor biology.
      Considering NO as a signal molecule we have studied the impact of NO release on
      processes of generation of H2O2 in different experimental systems including
      pleural effusions (PE) of lung cancer patients, human polymorphonuclear
      leukocytes (PMNs), and rat thymocytes. It was found that PE of lung cancer
      patients contain a high level of [NO2-+NO3-], i.e. 43.4 25.6 microM (n=15), and
      PE cells could effectively generate H2O2 in response to lectins from Viscum album
      (VAA), Phaseolus vulgaris (PHA), and Pisum sativum (PSA) as well as to menadione.
      A positive correlation between the [NO2-+NO3-] concentration and menadione
      induced H2O2 generation (r=0.1964) was found, whereas the [NO2-+NO3-]
      concentration and lectin-induced H2O2 generation (PHA, r=-0.4099; PSA, r=-0.3949;
      VAA, r=-0.3225) were negatively correlated. Notably, an increase of H2O2
      generation by PE cells was determined in the range of 20-35 microM [NO2-+NO3-].
      When PMNs and rat thymocytes were treated with a donor of NO (sodium
      nitroprusside), the release of H2O2 in response to lectins or menadione was
      decreased in a dose-dependent manner. The end products of NO biochemistry,
      assayed as KNO2 and KNO3, were not able to affect significantly the H2O2
      generation processes. In conclusion, the data indicate that the potential for
      triggered H2O2-generation of cells is modulated markedly by the presence of NO or
      derived reaction compounds. This relation may play an important role in the
      pathogenesis of PE malignancies with potential relevance for therapeutic
      strategies.

PMID- 10087332
TI  - Copper-nitrilotriacetate (Cu-NTA) is a potent inducer of proliferative response
      both in liver and kidney but is a complete renal carcinogen.
AB  - Earlier we have shown that ferric-nitrilotriacetate (Fe-NTA) is a hepatic as well
      as renal tumor promoter and acts by elaborating oxidative stress. In this study
      we show that copper-nitrilotriacetate (Cu-NTA) is a potent inducer of
      proliferative response both in liver and kidney but is a complete renal
      carcinogen. Similar to Fe-NTA, Cu-NTA has an ability to induce hepatic ornithine
      decarboxylase (ODC) activity dose-dependently. The maximum induction in hepatic
      ODC activity was observed 12 h after Cu-NTA treatment. However, renal ODC
      activity showed no significant changes at any time point and dose regimen
      studied. Similarly, hepatic and renal DNA synthesis which are measured as
      [3H]thymidine incorporation were increased dose-dependently in both the organs
      after Cu-NTA treatment. Unlike Fe-NTA, Cu-NTA administration had no significant
      effect on hepatic and renal glutathione, and on the activities of glutathione
      reductase, glutathione-S-transferase and catalase. In liver, saline-alone, DEN
      alone, Cu-NTA-alone or DEN + Cu-NTA treated animals showed no hepatic tumors.
      Liver histology from only DEN-initiated and saline-treated control animals showed
      occasional appearance of a typical cell with large nucleus. Treatment of Cu-NTA
      to uninitiated and initiated animals showed more or less similar hepatic
      histology. Treatment of Cu-NTA to DEN-initiated animals resulted in the
      proliferative changes characterized by extensive hepatocellular hyperplasia. In
      case of kidney, the treatment of Cu-NTA to both the DEN-initiated and uninitiated
      animals led to the development of renal cell tumors. Treatment of Cu-NTA to the
      uninitiated animals produced renal cell tumors in about 18.7% animals. However,
      treatment of Cu-NTA to the DEN-initiated animals led to the development of renal
      cell tumors in 77.7% animals, of which most of the tumors were bilateral.
      However, DEN-initiated and saline-treated control animals showed no evidence of
      tumors. Our data indicate that Cu-NTA is a potent inducer of proliferative
      response both in liver and kidney but is a complete renal carcinogen.

PMID- 10087333
TI  - A re-examination of adult mouse nicotinic acetylcholine receptor channel
      activation kinetics.
AB  - 1. During routine sequencing of our mouse muscle alpha subunit acetylcholine
      receptor channel (AChR) cDNA clones, we detected a discrepancy with the GenBank
      database entry (accession X03986). At nucleotides 1305-7 (residue 433, in the M4
      domain) the database lists GTC which encodes a valine, while our putative 'wild
      type' cDNA had the nucleotides GCC, which encodes an alanine. No other sequence
      differences were found. 2. PCR amplification of genomic DNA confirmed that the
      BALB/C mouse alpha subunit gene has a T nucleotide at position 1306, and,
      therefore, that the protein has a V at position 433 in the M4 segment. 3. In
      order to determine the functional consequences of this difference, either wild
      type (V433) or mutant (A433) alpha subunits were co-expressed in HEK cells with
      mouse beta, epsilon and delta subunits. Single-channel currents were recorded in
      cell-attached patches, and rate and equilibrium constants were estimated from
      open and closed durations obtained from a range of ACh concentrations. No
      significant differences were found between the activation rate constants or
      equilibrium constants of the V433 and A433 variants. 4. Kinetic modelling of
      alphaV433 AChR suggests that the two transmitter binding sites have similar
      dissociation equilibrium constants for acetylcholine ( approximately 160 microM
      in 142 mM extracellular KCl). 5. Diliganded AChRs occupy a closed state that has
      a lifetime of approximately 1 ms. The rate constants for entering and leaving
      this state do not vary with the ACh concentration. 6. The kinetics of a mutant
      AChR that causes a slow channel congenital myaesthenic syndrome, alphaG153S, was
      re-examined. The properties of this mutant were similar with a V or an A at
      position alpha433.

PMID- 10087334
TI  - Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L
      type Ca2+ channel gene expression.
AB  - 1. We investigated whether insulin-like growth factor-1 (IGF-1), an endogenous
      potent activator of skeletal muscle proliferation and differentiation, enhances L
      type Ca2+ channel gene expression resulting in increased functional voltage
      sensors in single skeletal muscle cells. 2. Charge movement and inward Ca2+
      current were recorded in primary cultured rat myoballs using the whole-cell
      configuration of the patch-clamp technique. Ca2+ current and maximum charge
      movement (Qmax) were potentiated in cells treated with IGF-1 without significant
      changes in their voltage dependence. Peak Ca2+ current in control and IGF-1
      treated cells was -7.8 +/- 0.44 and -10. 5 +/- 0.37 pA pF-1, respectively (P <
      0.01), whilst Qmax was 12.9 +/- 0.4 and 22.0 +/- 0.3 nC microF-1, respectively (P
      < 0.01). 3. The number of L-type Ca2+ channels was found to increase in the same
      preparation. The maximum binding capacity (Bmax) of the high-affinity radioligand
      [3H]PN200-110 in control and IGF-1-treated cells was 1.21 +/- 0.25 and 3.15 +/-
      0.5 pmol (mg protein)-1, respectively (P < 0.01). No significant change in the
      dissociation constant for [3H]PN200-110 was found. 4. Antisense RNA amplification
      showed a significant increase in the level of mRNA encoding the L-type Ca2+
      channel alpha1-subunit in IGF-1-treated cells. 5. This study demonstrates that
      IGF-1 regulates charge movement and the level of L-type Ca2+ channel alpha1
      subunits through activation of gene expression in skeletal muscle cells.

PMID- 10087335
TI  - Erythropoietin modulates intracellular calcium in a human neuroblastoma cell
      line.
AB  - 1. Recent investigations have shown that the glycoprotein erythropoietin (Epo)
      and its specific receptor (EpoR) are present in the mammalian brain including
      human, monkey and mouse. These findings suggest a local action of Epo in the
      nervous system. The aim of this study was to elucidate a possible functional
      interaction of Epo with neuronal cells. 2. To examine the influence of externally
      applied Epo on Ca2+ homeostasis the human neuroblastoma cell line SK-N-MC was
      chosen as a suitable in vitro model for undifferentiated neuronal cells. 3.
      Expression of the EpoR in SK-N-MC cells was detected by reverse transcription
      PCR, Western blot and immunofluorescence analysis. 4. Patch-clamp studies of SK-N
      MC cells confirmed the expression of T-type Ca2+ channels, whose peak macroscopic
      current was increased by the addition of recombinant human Epo (rhEpo) to the
      bathing medium. 5. Confocal laser scanning microscopy analysis of SK-N-MC cells
      confirmed a transient increase in intracellular free [Ca2+] in response to
      externally applied rhEpo. 6. The transient response to Epo was dependent on
      external Ca2+ and remained even after depletion of internal Ca2+ stores by
      caffeine or thapsigargin. However, after depletion the response to Epo was absent
      when cells were superfused with the T-type Ca2+ channel blocker flunarizine. 7.
      This study demonstrates that Epo can interact with neuronal cells by affecting
      Ca2+ homeostasis through an increase in Ca2+ influx via plasma membrane T-type
      voltage-dependent Ca2+ channels.

PMID- 10087336
TI  - Regulation of Cl- secretion in seawater fish (Dicentrarchus labrax) gill
      respiratory cells in primary culture.
AB  - 1. Primary cultures of sea bass (Dicentrarchus labrax) gill cells grown on
      permeable membranes form a highly differentiated tight epithelium composed of
      respiratory-like cells. This preparation was also found to provide a functional
      model for investigating the hormonal regulation of Cl- secretion. 2. In control
      conditions, i.e. in the absence of hormones or other stimuli, the cultured
      epithelium showed a short-circuit current (Isc) of 8.8 +/- 0.4 microA cm-2, a
      transepithelial potential (Vt) of 28.6 +/- 0.6 mV (serosal side positive), and a
      transepithelial resistance (Rt) of 5026 +/- 127 Omega cm2. Addition of 50 nM PGE2
      caused a stimulation of Isc, Vt and transepithelial conductance, Gt. The increase
      in Isc was probably due to the elevation in Cl- secretion, since it could be
      correlated with the stimulation of serosal to mucosal 36Cl- flux. Application of
      the neurohypophyseal peptide arginine vasotocin (AVT; 50 nM) or the beta
      adrenergic agonist isoproterenol (isoprenaline; 0. 5 microM) evoked a stimulation
      in Cl- secretion, as was shown by the increases in Isc and Gt. The excitatory
      effect of isoproterenol followed by the inhibitory action of propranolol, a beta
      adrenergic antagonist, suggested the presence of beta-adrenergic receptors.
      Noradrenaline (0.1 microM) elicited a reduction in Isc, Vt and Gt, which was
      counterbalanced by the addition of phentolamine, an alpha-adrenergic antagonist.
      This suggested an activation of alpha-adrenergic receptors. 3. This study
      provides evidence for hormonal control of the Cl- secretion in sea bass gill
      respiratory cells in culture, involving AVT, prostaglandin (PGE2), and beta- and
      alpha-adrenergic receptors.

PMID- 10087337
TI  - Modulation of the decay of Ca2+-activated Cl- currents in rabbit portal vein
      smooth muscle cells by external anions.
AB  - 1. The effects of external anions on the decay kinetics of Ca2+-activated Cl-
      currents (ICl(Ca)) were studied in smooth muscle cells isolated from rabbit
      portal vein using the perforated patch whole-cell voltage clamp technique. 2. In
      normal NaCl-containing external solution the decay of spontaneous Ca2+-activated
      Cl- currents (STICs) and Ca2+-activated Cl- 'tail' currents (Itail) was described
      by a single exponential with a time constant (tau) that was prolonged by external
      anions which are more permeable than Cl- (Br-, I- and SCN-) and accelerated by
      less permeant anions. However, intracellular I- did not affect the tau of STICs
      and Itail. 3. There was a positive correlation between the ability of an external
      anion to affect the decay tau of ICl(Ca) and its permeability relative to Cl-. 4.
      The voltage dependence of STIC and Itail decay was not affected by external or
      internal anions. 5. External permeating anions were not obligatory for activation
      of ICl(Ca) and STIC tau was not altered in Cl--free external solution. 6.
      Modulation of tau by mole fractions of SCN- and Cl- ions was fitted by a logistic
      curve, suggesting competition between SCN- and Cl- ions for a binding site. 7. In
      conclusion, external anions affect the decay of ICl(Ca) by a mechanism compatible
      with an interaction with a binding site which modulates Cl- channel kinetics.

PMID- 10087338
TI  - Isoform-specific regulation of the sodium pump by alpha- and beta-adrenergic
      agonists in the guinea-pig ventricle.
AB  - 1. Guinea-pig ventricle was used in the RNase protection assays to determine
      which alpha-isoforms of the Na+-K+ pumps are present, and ventricular myocytes
      were used in whole cell patch clamp studies to investigate the actions of alpha-
      and beta-adrenergic agonists on Na+-K+ pump current. 2. RNase protection assays
      showed that two isoforms of the alpha-subunit of the Na+-K+-ATPase are present in
      guinea-pig ventricle. The mRNA for the alpha1-isoform comprises 82 % of the total
      pump message, the rest being the alpha2-isoform. 3. We have previously shown that
      beta-adrenergic agonists affect Na+-K+ pump current (Ip) through a protein kinase
      A (PKA)-dependent pathway. We now show that these beta-effects are targeted to
      the alpha1-isoform of the Na+-K+ pumps. 4. We have also previously shown that
      alpha-adrenergic agonists increase Ip through a protein kinase C (PKC)-dependent
      pathway. We now show that these alpha-isoform effects are targeted to the alpha2
      isoform of the Na+-K+ pumps. 5. These results suggest the effects of adrenergic
      activation on Na+-K+ pump activity in the heart can be regionally specific,
      depending on which alpha-isoform of the Na+-K+ pump is expressed.

PMID- 10087339
TI  - Adrenergic control of the ultrarapid delayed rectifier current in canine atrial
      myocytes.
AB  - 1. The effects of adrenergic stimulation on the ultrarapid delayed rectifier K+
      current (IKur,d) of dog atrial myocytes was studied with patch-clamp methods. 2.
      Isoproterenol (isoprenaline) increased IKur,d in a concentration-dependent
      fashion with an EC50 of 7.3 +/- 0.8 nM. The effect of isoproterenol was blocked
      by propranolol, mimicked by forskolin and 8-bromo-cAMP, and prevented by
      inhibition of protein kinase A. 3. Phenylephrine (in the presence of propranolol)
      increased IKur,d with an EC50 of 0.49 +/- 0.06 microM. The effect of
      phenylephrine was blocked by prazosin, prevented by inhibition of protein kinase
      C, and mimicked by activation of protein kinase C with phorbol ester. 4.
      Phenylephrine significantly abbreviated canine atrial action potential duration
      in the absence of tetraethylammonium (TEA). When TEA was present under both
      control conditions and in the presence of phenylephrine, phenylephrine failed to
      alter canine atrial repolarization. 5. We conclude that beta- and alpha
      adrenergic stimulation increase IKur,d via protein kinase A and C, respectively,
      and that the induced changes in IKur,d may play a role in adrenergic control of
      canine atrial repolarization.

PMID- 10087340
TI  - Sequential activation of different Ca2+ entry pathways upon cholinergic
      stimulation in mouse pancreatic acinar cells.
AB  - 1. We have studied capacitative calcium entry (CCE) under different experimental
      conditions in fura-2-loaded mouse pancreatic acinar cells by digital microscopic
      fluorimetry. CCE was investigated during [Ca2+]i decay after cell stimulation
      with a supramaximal concentration of ACh (10 microM) or during Ca2+ readmission
      in Ca2+-depleted cells (pretreated with thapsigargin or ACh). 2. La3+ and Zn2+
      (100 microM) inhibited CCE during Ca2+ readmission but had negligible effects
      during ACh decay. In contrast flufenamic acid (100 microM), an inhibitor of non
      selective cation channels, genistein (10 microM), a broad-range tyrosine kinase
      inhibitor, and piceatannol (10 microM), an inhibitor specific for non-receptor
      Syk tyrosine kinase, inhibited CCE during ACh decay but not during Ca2+
      reintroduction. 3. Simultaneous detection of Mn2+ entry and [Ca2+]i measurement
      showed that, in the presence of extracellular calcium, application of 100 microM
      Mn2+ during ACh decay resulted in manganese influx without alteration of calcium
      influx, whilst when applied during Ca2+ readmission, Mn2+ entry was significantly
      smaller and induced a clear inhibition of CCE. 4. Application of the specific
      protein kinase C inhibitor GF109293X (3 microM) reduced CCE in Ca2+-depleted
      cells, whereas the activator phorbol 12-myristate, 13-acetate (3 microM)
      increased Ca2+ entry. 5. Based on these results we propose that cholinergic
      stimulation of mouse pancreatic acinar cells induces Ca2+ influx with an initial
      phase operated by a non-specific cation channel, sensitive to flufenamic acid and
      tyrosine kinase inhibitors but insensitive to lanthanum and divalent cations,
      followed by a moderately Ca2+-selective conductance inhibited by lanthanum and
      divalent cations.

PMID- 10087341
TI  - Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient
      and L-type Ca2+ current in rat ventricular myocytes.
AB  - 1. Microtubules form part of the cytoskeleton. Their role in adult ventricular
      myocytes is not well understood although microtubule proliferation has previously
      been linked with reduced contractile function. 2. We investigated the effect of
      the anti-tumour drug taxol, a known microtubule polymerizing agent, on Ca2+
      handling in adult rat ventricular myocytes. 3. Treatment of cells with taxol
      caused proliferation of microtubules. 4. In taxol-treated cells there was a
      reduction in the amplitude of contraction, no significant effect on the amplitude
      of L-type Ca2+ current, but a significant reduction in the amplitude of the Ca2+
      transient. 5. Caffeine was used to release Ca2+ from the sarcoplasmic reticulum
      (SR). There was a significant reduction in the ratio of electrically stimulated :
      caffeine-induced Ca2+ transients in taxol-treated cells. This observation is
      consistent with the hypothesis that taxol reduces fractional SR Ca2+ release. 6.
      We suggest that the negative inotropic effect of taxol may, at least in part, be
      the result of reduced release of Ca2+ from the SR. Microtubules may be important
      regulators of Ca2+ handling in the heart.

PMID- 10087342
TI  - Voltage inactivation of Ca2+ entry and secretion associated with N- and P/Q-type
      but not L-type Ca2+ channels of bovine chromaffin cells.
AB  - 1. In this study we pose the question of why the bovine adrenal medullary
      chromaffin cell needs various subtypes (L, N, P, Q) of the neuronal high-voltage
      activated Ca2+ channels to control a given physiological function, i.e. the
      exocytotic release of catecholamines. One plausible hypothesis is that Ca2+
      channel subtypes undergo different patterns of inactivation during cell
      depolarization. 2. The net Ca2+ uptake (measured using 45Ca2+) into
      hyperpolarized cells (bathed in a nominally Ca2+-free solution containing 1.2 mM
      K+) after application of a Ca2+ pulse (5 s exposure to 100 mM K+ and 2 mM Ca2+),
      amounted to 0.65 +/- 0.02 fmol cell-1; in depolarized cells (bathed in nominally
      Ca2+-free solution containing 100 mM K+) the net Ca2+ uptake was 0.16 +/- 0.01
      fmol cell-1. 3. This was paralleled by a dramatic reduction of the increase in
      the cytosolic Ca2+ concentration, [Ca2+]i, caused by Ca2+ pulses applied to fura
      2-loaded single cells, from 1181 +/- 104 nM in hyperpolarized cells to 115 +/- 9
      nM in depolarized cells. 4. A similar decrease was observed when studying
      catecholamine release. Secretion was decreased when K+ concentration was
      increased from 1.2 to 100 mM; the Ca2+ pulse caused, when comparing the extreme
      conditions, the secretion of 807 +/- 35 nA of catecholamines in hyperpolarized
      cells and 220 +/- 19 nA in depolarized cells. 5. The inactivation by
      depolarization of Ca2+ entry and secretion occluded the blocking effects of
      combined omega-conotoxin GVIA (1 microM) and omega-agatoxin IVA (2 microM), thus
      suggesting that depolarization caused a selective inactivation of the N- and P/Q
      type Ca2+ channels. 6. This was strengthened by two additional findings: (i)
      nifedipine (3 microM), an L-type Ca2+ channel blocker, suppressed the fraction of
      Ca2+ entry (24 %) and secretion (27 %) left unblocked by depolarization; (ii)
      FPL64176 (3 microM), an L-type Ca2+ channel 'activator', dramatically enhanced
      the entry of Ca2+ and the secretory response in depolarized cells. 7. In voltage
      clamped cells, switching the holding potential from -80 to -40 mV promoted the
      loss of 80 % of the whole-cell inward Ca2+ channel current carried by 10 mM Ba2+
      (IBa). The residual current was blocked by 80 % upon addition of 3 microM
      nifedipine and dramatically enhanced by 3 microM FPL64176. 8. Thus, it seems that
      the N- and P/Q-subtypes of calcium channels are more prone to inactivation at
      depolarizing voltages than the L-subtype. We propose that this different
      inactivation might occur physiologically during different patterns of action
      potential firing, triggered by endogenously released acetylcholine under various
      stressful conditions.

PMID- 10087343
TI  - cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent
      sodium channel SNS.
AB  - 1. Protein kinase A (PKA) modulation of tetrodotoxin-resistant (TTX-r) voltage
      gated sodium channels may underly the hyperalgesic responses of mammalian sensory
      neurones. We have therefore examined PKA phosphorylation of the cloned alpha
      subunit of the rat sensory neurone-specific TTX-r channel SNS. Phosphorylation of
      SNS was compared with that of a mutant channel, SNS(SA), in which all five PKA
      consensus sites (RXXS) within the intracellular I-II loop had been eliminated by
      site-directed mutagenesis (serine to alanine). 2. In vitro PKA phosphorylation
      and tryptic peptide mapping of SNS and mutant SNS(SA) I-II loops expressed as
      glutathione-S-transferase (GST) fusion proteins confirmed that the five mutated
      serines were the major PKA substrates within the SNS I-II loop. 3. SNS and
      SNS(SA) channels were transiently expressed in COS-7 cells and their
      electrophysiological properties compared. In wild-type SNS channels, forskolin
      and 8-bromo cAMP produced effects consistent with PKA phosphorylation. Mutant
      SNS(SA) currents, however, were not significantly affected by either agent. Thus,
      elimination of the I-II loop PKA consensus sites caused a marked reduction in PKA
      modulation of wild-type channels. 4. Under control conditions, the voltage
      dependence of activation of SNS(SA) current was shifted to depolarized potentials
      compared with SNS. This was associated with a slowing of SNS(SA) current
      inactivation at hyperpolarized potentials and suggested a tonic PKA
      phosphorylation of wild-type channels under basal conditions.5. We conclude that
      the major substrates involved in functional PKA modulation of the SNS channel are
      located within the intracellular I-II loop.

PMID- 10087344
TI  - ATP counteracts the rundown of gap junctional channels of rat ventricular
      myocytes by promoting protein phosphorylation.
AB  - 1. The degree of cell-to-cell coupling between ventricular myocytes of neonatal
      rats appeared well preserved when studied in the perforated version of the patch
      clamp technique or, in double whole-cell conditions, when ATP was present in the
      patch pipette solution. In contrast, when ATP was omitted, the amplitude of
      junctional current rapidly declined (rundown). 2. To examine the mechanism(s) of
      ATP action, an 'internal perfusion technique' was adapted to dual patch clamp
      conditions, and reintroduction of ATP partially reversed the rundown of
      junctional channels. 3. Cell-to-cell communication was not preserved by a non
      hydrolysable ATP analogue (5'-adenylimidodiphosphate, AMP-PNP), indicating that
      the effect most probably did not involve direct interaction of ATP with the
      channel-forming proteins. 4. An ATP analogue supporting protein phosphorylation
      but not active transport processes (adenosine 5'-O-(3-thiotriphosphate),
      ATPgammaS) maintained normal intercellular communication, suggesting that the
      effect was due to kinase activity rather than to altered intracellular Ca2+. 5. A
      broad spectrum inhibitor of endogenous serine/threonine protein kinases (H7)
      reversibly reduced the intercellular coupling. A non-specific exogenous protein
      phosphatase (alkaline phosphatase) mimicked the effects of ATP deprivation. The
      non-specific inhibition of endogenous protein phosphatases resulted in the
      preservation of substantial cell-to-cell communication in ATP-free conditions. 6.
      The activity of gap junctional channels appears to require both the presence of
      ATP and protein kinase activity to counteract the tonic activity of endogenous
      phosphatase(s).

PMID- 10087345
TI  - Two components of transmitter release from the chick ciliary presynaptic terminal
      and their regulation by protein kinase C.
AB  - 1. A study was made of the effects of phorbol ester (phorbol 12-myristate 13
      acetate, PMA, 0.1 microM) on the two components of evoked transmitter release,
      namely the fast synchronous and the slow asynchronous components, from the giant
      presynaptic terminal of the chick ciliary ganglion. The excitatory postsynaptic
      currents (EPSCs) were recorded under whole-cell voltage clamp of the postsynaptic
      neuron. 2. The decay time constant of the slow component was prolonged by
      replacing Ca2+ with Sr2+. In 5 mM [Sr2+]o the fast component decayed with a time
      constant of 2.6 +/- 1.4 ms whereas the slow component decayed with a time
      constant of 19 +/- 7 ms. 3. When stimulated with twin pulses with a short
      interpulse interval, the fast component of the second EPSC was often depressed
      whereas the slow component was usually facilitated. Both components were
      positively dependent on [Sr2+]o in a saturable manner, but the fast component
      approached its maximum at a lower [Sr2+]o than the slow component. 4. PMA
      potentiated both the fast and slow components to a similar extent and with a
      similar time course. For each component, the effect of PMA was less potent at
      high [Sr2+]o than at low [Sr2+]o. For either the fast or the slow component the
      PMA-induced potentiation was accompanied by a reduction in the paired-pulse ratio
      (PPR). 5. Despite the different dissociation constant for dextran-conjugated fura
      2, the fluorescent ratio for intraterminal [Sr2+] ([Sr2+]i) decayed to the
      baseline after the nerve-evoked increment with a time course similar to that for
      [Ca2+]i, suggesting that intraterminal Sr2+ is buffered less efficiently than
      Ca2+. PMA did not increase the [Sr2+]i transients produced by stimulation of the
      presynaptic oculomotor nerve. 6. It is suggested that protein kinase C (PKC)
      modulates both the fast and slow components through common molecular mechanisms
      that upregulate the Sr2+ sensitivity of the vesicle fusion probability.

PMID- 10087346
TI  - The rostral ventrolateral medulla mediates the sympathoactivation produced by
      chemical stimulation of the rat nasal mucosa.
AB  - 1. We sought to outline the brainstem circuit responsible for the increase in
      sympathetic tone caused by chemical stimulation of the nasal passages with
      ammonia vapour. Experiments were performed in alpha-chloralose-anaesthetized,
      paralysed and artificially ventilated rats. 2. Stimulation of the nasal mucosa
      increased splanchnic sympathetic nerve discharge (SND), elevated arterial blood
      pressure (ABP), raised heart rate slightly and inhibited phrenic nerve discharge.
      3. Bilateral injections of the broad-spectrum excitatory amino acid receptor
      antagonist kynurenate (Kyn) into the rostral part of the ventrolateral medulla
      (RVLM; rostral C1 area) greatly reduced the effects of nasal mucosa stimulation
      on SND (-80 %). These injections had no effect on resting ABP, resting SND or the
      sympathetic baroreflex. 4. Bilateral injections of Kyn into the ventrolateral
      medulla at the level of the obex (caudal C1 area) or into the nucleus tractus
      solitarii (NTS) greatly attenuated the baroreflex and significantly increased the
      baseline levels of both SND and ABP. However they did not reduce the effect of
      nasal mucosa stimulation on SND. 5. Single-unit recordings were made from 39
      putative sympathoexcitatory neurons within the rostral C1 area. Most neurons (24
      of 39) were activated by nasal mucosa stimulation (+65.8 % rise in discharge
      rate). Responding neurons had a wide range of conduction velocities and included
      slow-conducting neurons identified previously as C1 cells. The remaining putative
      sympathoexcitatory neurons were either unaffected (n = 8 neurons) or inhibited (n
      = 7) during nasal stimulation. We also recorded from ten respiratory-related
      neurons, all of which were silenced by nasal stimulation. 6. In conclusion, the
      sympathoexcitatory response to nasal stimulation is largely due to activation of
      bulbospinal presympathetic neurons within the RVLM. We suggest that these neurons
      receive convergent and directionally opposite polysynaptic inputs from arterial
      baroreceptors and trigeminal afferents. These inputs are integrated within the
      rostral C1 area as opposed to the NTS or the caudal C1 area.

PMID- 10087347
TI  - Temporal overlap of excitatory and inhibitory afferent input in guinea-pig CA1
      pyramidal cells.
AB  - 1. The temporal interaction of evoked synaptic excitation and GABAA-mediated
      inhibition was examined in CA1 pyramidal cells. Single and paired intracellular
      recordings were carried out in pyramidal cell dendrites and somata, and
      interneurons of the guinea-pig hippocampal slice. Current-clamp, sharp electrode
      and whole-cell voltage-clamp recordings were made. 2. Kinetics of dendritic and
      somatic inhibitory responses were similar. Notably, kinetics of dendritic unitary
      IPSPs were as fast as kinetics of somatic unitary IPSPs. 3. GABAA-mediated
      influences were present throughout the orthodromic pyramidal cell EPSP/EPSC.
      Comparison of the kinetics of pharmacologically isolated monosynaptic IPSPs,
      IPSCs and inhibitory conductances (g GABAA), showed fastest kinetics for g GABAA.
      Close temporal overlap was observed between monosynaptic g GABAA and the rising
      phase of the evoked EPSP/EPSC. The onset of g GABAA coincided with or preceded
      onset of the EPSP/EPSC. 4. Onsets of feedforward IPSPs coincided with the rising
      phase of the pyramidal cell EPSP in > 80 % of paired recordings. Fastest
      feedforward inhibitory responses exerted near complete overlap with evoked
      excitation. 5. Onsets of recurrent IPSPs did not occur during the rising phase of
      the evoked EPSP, but > 3.0 ms after the peak of the pyramidal cell EPSP. 6.
      Orthodromically evoked interneuron spikes were observed at stimulation
      intensities that were below the threshold for eliciting EPSPs in concomitantly
      recorded pyramidal cells. The activation of feedforward inhibitory responses by
      weakest excitatory input, and the large temporal overlap between feedforward
      inhibition and evoked excitation, suggest that in situ any excitatory input in
      CA1 is effectively controlled by fast synaptic inhibition.

PMID- 10087348
TI  - Quantal size is correlated with receptor cluster area at glycinergic synapses in
      the rat brainstem.
AB  - 1. Whole-cell patch electrode recordings of glycinergic miniature inhibitory
      postsynaptic currents (mIPSCs) were obtained in neurons of the rat anteroventral
      cochlear nucleus (AVCN). Mean mIPSC peak amplitude was found to vary considerably
      between AVCN neurons (range, -19.1 to -317.9 pA; mean +/- s.d., -159.1 +/- 100.7
      pA; 14 cells). 2. Immunolabelling of glycinergic receptor clusters in AVCN
      neurons was performed using antibodies against the glycine receptor clustering
      protein gephyrin. Measurements of the area of gephyrin immunoreactive clusters
      were obtained using confocal fluorescence microscopy. These measurements showed a
      large variability in cluster area, not only in the same cell (mean coefficient of
      variation, c.v., 0.66 +/- 0.18; 16 cells), but also in mean cluster area between
      cells (range, 0.21-0.84 microm2; 16 cells). 3. A possible relationship between
      mIPSC amplitude and receptor cluster area was investigated in a further series of
      experiments, in which mIPSCs recordings and immunolabelling of glycine receptor
      clusters were obtained for the same cells. In these experiments, AVCN neurons
      were identified using intracellular labelling with neurobiotin. Successful
      results using a combination of whole-cell recordings, neurobiotin identification
      and immunolabelling were obtained for a total of 10 AVCN neurons. Analysis of the
      results revealed a positive, statistically significant correlation between mean
      receptor cluster size and mean mIPSC amplitude (P < 0.05, 10 cells, Spearman's
      correlation test). 4. These results provide direct experimental evidence
      supporting a hypothesis of central glycinergic transmission in which synaptic
      strength may be regulated by changes in the size of the postsynaptic receptor
      region.

PMID- 10087349
TI  - Changes in properties and neurosteroid regulation of GABAergic synapses in the
      supraoptic nucleus during the mammalian female reproductive cycle.
AB  - 1. GABAA receptor-mediated synaptic innervation of oxytocin neurones in the
      supraoptic nucleus (SON) was analysed in adult female rats going through their
      first reproductive cycle by recording the spontaneous inhibitory postsynaptic
      currents (sIPSCs) at six stages of female reproduction. 2. During pregnancy we
      observed a reduction in the interval between monoquantal sIPSCs. The synaptic
      current amplitude, current decay and neurosteroid sensitivity of postsynaptic
      GABAA receptors observed at this stage were not distinguishable from those
      measured in virgin stage SON. 3. Upon parturition an increase in monoquantal
      synaptic current decay occurred, whereas potentiation by the progesterone
      metabolite allopregnanolone (3alpha-OH-DHP) was suppressed. 4. Throughout a
      substantial part of the lactation period the decay of synaptic currents remained
      attenuated, whilst the potentiation by 3alpha-OH-DHP remained suppressed. 5.
      Several weeks after the end of lactation sIPSC intervals, their current decay
      velocity as well as the potentiation by 3alpha-OH-DHP were restored to pre
      pregnancy levels, which is indicative of the cyclical nature of synaptic
      plasticity in the adult SON. 6. Competitive polymerase chain reaction (PCR)
      analysis showed that virgin animals expressed alpha1 and alpha2 GABAA receptor
      subunit mRNA at a relative ratio of 2 : 1 compared with beta-actin. After
      pregnancy both alpha1 and alpha2 subunit mRNA levels were transiently increased,
      although at a relative ratio of 1 : 4, in line with the hypothesis that alpha2
      plays a large role in postsynaptic receptor functioning. During post-lactation
      both alpha subunits were downregulated. 7. We propose that synaptic remodelling
      in the SON during pregnancy includes changes in the putative number of GABA
      release sites per neurone. At parturition, and during the two consecutive weeks
      of lactation, a subtype of postsynaptic GABAA receptors was observed, distinct
      from the one being expressed before and during pregnancy. Synaptic current
      densities, calculated in order to compare the impact of synaptic inhibition,
      showed that, in particular, the differences in 3alpha-OH-DHP potentiation of
      these two distinct GABAA receptor subtypes produce robust shifts in the impact of
      synaptic inhibition of oxytocin neurones at the different stages of female
      reproduction.

PMID- 10087350
TI  - Initiation of peristalsis by circumferential stretch of flat sheets of guinea-pig
      ileum.
AB  - 1. Segments of isolated guinea-pig intestine, 12 mm long, were distended slowly
      by intraluminal fluid infusion or by mechanical stretch as either a tube or flat
      sheet. In all cases, at a constant threshold length, a sudden, large amplitude
      contraction of the circular muscle occurred orally, corresponding to the
      initiation of peristalsis. 2. Circumferential stretch of flat sheet preparations
      evoked graded contractions of the longitudinal muscle (the 'preparatory phase'),
      which were maintained during circular muscle contraction. This suggests that the
      lengthening reported during the emptying phase of peristalsis is due to
      mechanical interactions. 3. The threshold for peristalsis was lower with more
      rapid stretches and was also lower in long preparations (25 mm) compared with
      short preparations (5-10 mm), indicating that ascending excitatory pathways play
      a significant role in triggering peristalsis. 4. Stretching a preparation beyond
      the threshold for peristalsis evoked contractions of increasing amplitude; thus
      peristalsis is graded above its threshold. However, during suprathreshold stretch
      maintained at a constant length, contractions of the circular muscle quickly
      declined in amplitude and frequency. 5. Circular muscle cells had a resting
      membrane potential approximately 6 mV more negative than the threshold for action
      potentials. During slow circumferential stretch, subthreshold graded excitatory
      motor input to the circular muscle occurred, prior to the initiation of
      peristalsis. However, peristalsis was initiated by a discrete large excitatory
      junction potential (12 +/- 2 mV) which evoked bursts of smooth muscle action
      potentials and which probably arose from synchronized firing of ascending
      excitatory neuronal pathways.

PMID- 10087351
TI  - Preserved arterial flow secures hepatic oxygenation during haemorrhage in the
      pig.
AB  - 1. This study examined the extent of liver perfusion and its oxygenation during
      progressive haemorrhage. We examined hepatic arterial flow and hepatic
      oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The
      hepatic surface oxygenation was assessed by near-infrared spectroscopy and the
      hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy
      of the hepatic flow. 2. Stepwise haemorrhage until circulatory collapse resulted
      in proportional reductions in cardiac output and in arterial, central venous and
      pulmonary wedge pressures. While heart rate increased, pulmonary arterial
      pressure remained stable. In addition, renal blood flow decreased, renal vascular
      resistance increased and there was elevated noradrenaline spill-over. Further,
      renal surface oxygenation was lowered from the onset of haemorrhage. 3.
      Similarly, the portal blood flow was reduced in response to haemorrhage, and, as
      for the renal flow, the reduced splanchnic blood flow was associated with an
      elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was
      only slightly reduced by haemorrhage, and surface oxygenation did not change. The
      hepatic oxygen uptake was maintained until the blood loss represented more than
      30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic
      catecholamine uptake was reduced, and the lactate uptake approached zero. 4.
      Subsequent reduction of cardiac output and portal blood flow elicited a selective
      dilatation of the hepatic arterial vascular bed. Due to this dilatation liver
      blood flow and hepatic cell oxygenation and metabolism were preserved prior to
      circulatory collapse.

PMID- 10087353
TI  - Task-dependent modulation of 15-30 Hz coherence between rectified EMGs from human
      hand and forearm muscles.
AB  - 1. Recent reports have shown task-related changes in oscillatory activity in the
      15-30 Hz range in the sensorimotor cortex of human subjects and monkeys during
      skilled hand movements. In the monkey these oscillations have been shown to be
      coherent with oscillatory activity in the electromyographic activity of hand and
      forearm muscles. 2. In this study we investigated the modulation of oscillations
      in the electromyogram (EMG) of human volunteers during tasks requiring precision
      grip of two spring-loaded levers. 3. Two tasks were investigated: in the 'hold'
      task, subjects were required to maintain a steady grip force (ca 2.1 N or 2.6 N)
      for 8 s. In the 'ramp' task, there was an initial hold period for 3 s (force ca
      2.1 N) followed by a linear increase in grip force over a 2 s period. The task
      ended with a further steady hold for 3 s at the higher force level (ca 2.6 N). 4.
      Surface EMGs were recorded from five hand and forearm muscles in 12 subjects. The
      coherence of oscillatory activity was calculated between each muscle pair.
      Frequencies between 1 and 100 Hz were analysed. 5. Each subject showed a peak in
      the coherence spectra in the 15-30 Hz bandwidth during the hold task. This
      coherence was absent during the initial movement of the levers. During the ramp
      task the coherence in the 15-30 Hz range was also significantly reduced during
      the movement phase, and significantly increased during the second hold period,
      relative to the initial hold. 6. There was coherence between the simultaneously
      recorded magnetoencephalogram (MEG) and EMG during steady grip in the hold task;
      this coherence disappeared during the initial lever movement. Using a single
      equivalent current dipole source model, the coherent cortical activity was
      localized to the hand region of the contralateral motor cortex. This suggests
      that the EMG-EMG coherence was, therefore, at least in part, of cortical origin.
      7. The results are discussed in terms of a possible role for synchrony in the
      efficient recruitment of motor units during maintained grip.

PMID- 10087352
TI  - Role of nitric oxide in the regulation of microvascular perfusion in human skin
      in vivo.
AB  - 1. Nitric oxide (NO) concentrations were measured in dialysate from healthy human
      skin, in vivo, both at rest and during the inflammatory response to intradermal
      histamine or bradykinin. Changes in dialysate NO concentration, measured by
      electrochemical detection, were related to changes in dermal vascular perfusion,
      measured using scanning laser Doppler imaging. 2. Basal NO concentration in
      dermal microdialysate was 0.60 +/- 0.14 microM (mean +/- s.e.m.). Following the
      intradermal injection of histamine, a transient, time-dependent increase in NO
      concentration was measured in areas of skin incorporating the weal and in others
      incorporating the flare. The increase in NO concentration was associated with an
      increase in dialysate cGMP concentration in both the weal and flare areas. 3.
      Addition of N G-nitro-l-arginine-methyl ester (L-NAME, 5 mM) to the probe
      perfusate resulted in an inhibition of the histamine-induced increase in NO and
      cGMP. Moreover, the reduction in dialysate NO concentration was associated with a
      reduction in dermal vascular flux, both under basal conditions and within the
      weal and flare response. 4. These results demonstrate, by the use of
      microdialysis, that vasoactive mediators can be measured in healthy human skin in
      vivo. They provide direct evidence that endogenous concentration of NO increases
      during the inflammatory weal and flare response to histamine and that the
      increase in dermal NO concentration is associated with increases in cGMP
      concentration and dermal vascular perfusion, thus confirming a role for NO in
      vasoregulation in human skin.

PMID- 10087354
TI  - Inspiration-promoting vagal reflex under NMDA receptor blockade in anaesthetized
      rabbits.
AB  - 1. This study describes a novel vagal respiratory reflex in anaesthetized
      rabbits. In contrast to the well-known inspiratory (I) off-switching by vagal
      afferent excitation, this vagal reflex initiates and maintains the central I
      activity of phrenic nerve discharges in rabbits pre-treated with antagonists of N
      methyl-D-aspartate-type excitatory amino acid receptors (NMDA-Rs). 2. Under NMDA
      R blockade with either dizocilpine (0.025-0.3 mg kg-1), D-2-amino-5
      phosphonopentanoic acid (AP5, 0.5-1 mg, i.c.v.) or ketamine (10 mg kg-1), vagal
      stimulation at low frequencies (5-40 Hz) during the I phase prevented or markedly
      delayed the spontaneous I termination. In contrast, stimulation of the same vagal
      afferent at the same intensity but at a higher frequency (100-160 Hz) during the
      I phase immediately terminated the I phase. 3. In non-vagotomized rabbits,
      maintaining the tidal volume at end-expiratory levels during the I phase
      prevented spontaneous I termination and maintained apneusis after NMDA-R blockade
      with dizocilpine. 4. Brief stimulation of vagal afferents at low frequency (5-40
      Hz) during the expiratory (E) phase constantly initiated phrenic I discharge
      after NMDA-R block. 5. We conclude that low-frequency discharge of vagal
      pulmonary stretch receptor afferents, as when lung volume is near functional
      residual capacity, promotes central I activity under NMDA-R blockade.

PMID- 10087355
TI  - Expression of insulin growth factor-1 splice variants and structural genes in
      rabbit skeletal muscle induced by stretch and stimulation.
AB  - 1. Skeletal muscle is a major source of circulating insulin growth factor-1 (IGF
      1), particularly during exercise. It expresses two main isoforms. One of the
      muscle IGF-1 isoforms (muscle L.IGF-1) is similar to the main liver IGF-1 and
      presumably has an endocrine action. The other muscle isoform as a result of
      alternative splicing has a different 3' exon sequence and is apparently designed
      for an autocrine/paracrine action (mechano-growth factor, MGF). Using RNase
      protection assays with a probe that distinguishes these differently spliced forms
      of IGF-1, their expression and also the expression of two structural genes was
      measured in rabbit extensor digitorum longus muscles subjected to different
      mechanical signals. 2. Within 4 days, stretch using plaster cast immobilization
      with the limb in the plantar flexed position resulted in marked upregulation of
      both forms of IGF-1 mRNA. Electrical stimulation at 10 Hz combined with stretch
      (overload) resulted in an even greater increase of both types of IGF-1
      transcript, whereas electrical stimulation alone, i.e. without stretch, resulted
      in no significant increase over muscle from sham-operated controls. Previously,
      it was shown that stretch combined with electrical stimulation of the dorsiflexor
      muscles in the adult rabbit results in a marked increase in muscle mass involving
      increases in both length and girth, within a few days. The expression of both
      systemic and autocrine IGF-1 growth factors provides a link between the
      mechanical signal and the marked increase in the structural gene expression
      involved in tissue remodelling and repair. 3. The expression of the beta actin
      gene was seen to be markedly upregulated in the stretched and
      stretched/stimulated muscles. It was concluded that the increased expression of
      this cytoskeletal protein gene is an indication that the production of IGF-1 may
      initially be a response to local damage. 4. Switches in muscle fibre phenotype
      were studied using a specific gene probe for the 2X myosin heavy chain gene. Type
      2X expression was found to decrease markedly with stimulation alone and when
      electrical stimulation was combined with stretch. Unlike the induction of IGF-1
      and beta actin, the decreased expression of the 2X myosin mRNA was less marked in
      the 'stretch only' muscles. This indicates that the interconversion of fibre type
      2X to 2A may in some situations be commensurate with, but not under the control
      of IGF-1.

PMID- 10087356
TI  - Sensitivity and kinetics of mouse rod flash responses determined in vivo from
      paired-flash electroretinograms.
AB  - 1. Electroretinograms (ERGs) were recorded corneally from C57BL/6J mice using a
      paired-flash procedure in which a brief test flash at time zero was followed at
      time tprobe by a bright probe flash of fixed strength, and in which the probe
      response amplitude was determined at time t = tprobe + 6 ms. Probe responses
      obtained in a series of paired-flash trials were analysed to derive A(t), a
      family of amplitudes that putatively represents the massed response of the rod
      photoreceptors to the test flash. A central aim was to obtain a mathematical
      description of the normalized derived response A(t)/Amo as a function of Itest,
      the test flash strength. 2. With fixed tprobe (80 <= tprobe <= 1200 ms), A(t)/Amo
      was described by the saturating exponential function [1 - exp(-ktItest)], where
      kt is a time-dependent sensitivity parameter. For t = 86 ms, a time near the peak
      of A(t), k86 was 7.0 +/- 1.2 (scotopic cd s m-2)-1 (mean +/- s. d.; n = 4). 3.
      A(t)/Amo data were analysed in relation to the equation below, a time-generalized
      form of the above exponential function in which (k86Itest) is replaced by the
      product [k86Itestu(t)], and where u(t) is independent of the test flash strength.
      The function u(t) was modelled as the product of a scaling factor gamma, an
      activation term 1 - exp[-alpha(t - td)2]), and a decay term exp(-t/tauomega):
      A(t)/Amo = 1 - exp[-k86Itestu(t)]; u(t) = gamma(1 - exp[-alpha(t - td)2](exp(
      t/tauomega) where td is a brief delay, tauomega is an exponential time constant,
      and alpha characterizes the acceleration of the activation term. For Itest up to
      approximately 2.57 scotopic cd s m-2, the overall time course of A(t) was well
      described by the above equation with gamma = 2.21, td = 3.1 ms, tauomega = 132 ms
      and alpha = 2.32 x 10-4 ms-2. An approximate halving of alpha improved the fit of
      the above equation to ERG a-wave and A(t)/Amo data obtained at t about 0-20 ms.
      4. Kinetic and sensitivity properties of A(t) suggest that it approximates the in
      vivo massed photocurrent response of the rods to a test flash, and imply that
      u(t) in the above equation is the approximate kinetic description of a unit, i.e.
      single photon, response.

PMID- 10087357
TI  - Ageing and the circadian and homeostatic regulation of human sleep during forced
      desynchrony of rest, melatonin and temperature rhythms.
AB  - 1. The circadian timing system has been implicated in age-related changes in
      sleep structure, timing and consolidation in humans. 2. We investigated the
      circadian regulation of sleep in 13 older men and women and 11 young men by
      forced desynchrony of polysomnographically recorded sleep episodes (total, 482; 9
      h 20 min each) and the circadian rhythms of plasma melatonin and core body
      temperature. 3. Stage 4 sleep was reduced in older people. Overall levels of
      rapid eye movement (REM) sleep were not significantly affected by age. The
      latencies to REM sleep were shorter in older people when sleep coincided with the
      melatonin rhythm. REM sleep was increased in the first quarter of the sleep
      episode and the increase of REM sleep in the course of sleep was diminished in
      older people. 4. Sleep propensity co-varied with the circadian rhythms of body
      temperature and plasma melatonin in both age groups. Sleep latencies were longest
      just before the onset of melatonin secretion and short sleep latencies were
      observed close to the temperature nadir. In older people sleep latencies were
      longer close to the crest of the melatonin rhythm. 5. In older people sleep
      duration was reduced at all circadian phases and sleep consolidation deteriorated
      more rapidly during the course of sleep, especially when the second half of the
      sleep episode occurred after the crest of the melatonin rhythm. 6. The data
      demonstrate age-related decrements in sleep consolidation and increased
      susceptibility to circadian phase misalignment in older people. These changes,
      and the associated internal phase advance of the propensity to awaken from sleep,
      appear to be related to the interaction between a reduction in the homeostatic
      drive for sleep and a reduced strength of the circadian signal promoting sleep in
      the early morning.

PMID- 10087358
TI  - Coming to term with GABA 
AB  - Oxytocin, the most powerful uterotonic agent known, is released from the
      pituitary gland in large amounts during parturition in all placental mammals
      studied so far, including humans. Although parturition can proceed in its
      absence, oxytocin is thought to play an important role (see Russell & Leng,
      1998). In the rat, pregnancy normally lasts for 21 days. About 24 h before the
      pups are born, increased production of prostaglandins by the uterus induces
      luteolysis, and ovarian progesterone production falls dramatically. This fall is
      an essential prelude to parturition; if prevented, then the rat pups will remain
      unborn. The fall leads to a further increase in prostaglandin production, and,
      directly or indirectly, to a host of changes that prepare the uterus and birth
      canal for parturition. In the last few hours of pregnancy, oxytocin receptors
      appear in high concentrations in the uterus, and establish a positive-feedback
      loop between the uterus and the hypothalamic oxytocin system. Uterine
      contractions, triggered by prostaglandins, excite the oxytocin cells, and
      oxytocin release triggers further prostaglandin production and further uterine
      contraction. Thus progesterone plays a critical role in the timing of parturition
      through its peripheral actions (see Leng & Brown, 1997). A paper in this issue of
      The Journal of Physiology (Brussaard et al. 1999) suggests that actions of
      progesterone at the oxytocin cells in the hypothalamus may also be important for
      parturition. Classically, progesterone acts through specific intracellular
      receptors to regulate gene expression. However, metabolites of progesterone can
      also have membrane actions, and in particular, allopregnanolone can act at GABAA
      receptors to potentiate the actions of GABA, depending upon the particular
      subunit composition of the receptor. GABA is an important neurotransmitter for
      oxytocin cells about 45 % of all synapses onto them contain GABA, and the total
      number of GABA synapses in the supraoptic nucleus is substantially higher in
      lactating animals than in virgins (El Majdoubi et al. 1997). The GABA innervation
      appears to play a role in patterning the pulsatile discharge of oxytocin cells
      that is observed both during parturition and during suckling-induced reflex milk
      ejection (Moos, 1995; Voisin et al. 1995). Brussaard et al. (1999) recorded GABAA
      receptor-mediated spontaneous monoquantal inhibitory postsynaptic currents
      (sIPSCs) from rat supraoptic neurones in hypothalamic slices in vitro. They found
      a higher incidence of sIPSCs in pregnant rats than in virgin rats, consistent
      with the observations of an increase in the density of GABA-containing synaptic
      boutons. Importantly, the sIPSCs were markedly prolonged in the presence of
      allopregnanolone. Taking into account the frequency and amplitude of sIPSCs, the
      action of allopregnanolone and the hypertrophy of oxytocin neurones in lactation
      (reflected in increased capacitance), Brussaard et al. (1999) inferred that the
      effective GABAA receptor-mediated synaptic current density was much greater in
      pregnant rats than in virgin or lactating rats. Thus the collapse of progesterone
      production at term may abruptly reduce the effectiveness of GABA inhibition, and
      thereby enhance the excitability of oxytocin cells. Clearly this may be important
      during parturition, but the effect may not persist for long. Indeed, within a day
      the duration of sIPSCs is significantly longer in the absence of
      allopregnanolone, which now has no significant effect. This seems to be due to a
      rapid switch in the types of a subunits inserted into the GABAA receptors. By mid
      lactation, a massive change in expression of GABAA receptor subunit mRNAs is
      apparent. With competitive polymerase chain reaction Brussaard and colleagues
      found that, while the expression of both a1 and a2 subunit mRNAs was increased,
      the ratio of a1 : a2 subunit mRNA expression was changed 8-fold in favour of a2
      subunit mRNA. (ABSTRACT TRUNCATED)

PMID- 10087359
TI  - 8th European Stroke Conference. Venice, Italy, April 7-10, 1999. Abstracts.

PMID- 10087361
TI  - Poster session I: risk factors and etiology 

PMID- 10087360
TI  - Poster session I: epidemiology 

PMID- 10087362
TI  - Poster session I: clotting and coagulation 

PMID- 10087363
TI  - Poster session I: recovery and rehabilitation 

PMID- 10087364
TI  - Poster session I: stroke outcome (Predictors) 

PMID- 10087365
TI  - Poster session I: interesting case 

PMID- 10087366
TI  - Poster session I: surgical aspects 

PMID- 10087367
TI  - Poster session I: hemorrhage 

PMID- 10087368
TI  - Poster session I: small vessel Disease/Vascular dementia 

PMID- 10087369
TI  - Platform session II A: neuroimaging 

PMID- 10087371
TI  - Platform session III A: vascular physiology CBF 

PMID- 10087370
TI  - Platform session II B: experimental 

PMID- 10087372
TI  - Platform session III B: epidemiology and risk factors I 

PMID- 10087373
TI  - Platform session IV: prevention 

PMID- 10087374
TI  - Poster session II: diagnosis neuroimaging 

PMID- 10087375
TI  - Poster session II: diagnosis ultrasound 

PMID- 10087376
TI  - Poster session II: acute stroke (Diagnosis and monitoring) 

PMID- 10087377
TI  - Poster session II: acute stroke (Symptoms and complications) 

PMID- 10087379
TI  - Poster session II: acute stroke (Treatment) 

PMID- 10087378
TI  - Poster session II: acute stroke (Clinical physiology) 

PMID- 10087381
TI  - Poster session II: management 

PMID- 10087380
TI  - Poster session II: ongoing trials 

PMID- 10087383
TI  - Platform session V A: Recovery/Physical therapy 

PMID- 10087382
TI  - Poster session II: experimental 

PMID- 10087384
TI  - Platform session V B: acute treatment - thrombolysis 

PMID- 10087385
TI  - Platform session VI: large trials - acute stroke 

PMID- 10087386
TI  - The artificial bladder.
AB  - An artificial bladder should provide adequate urine storage, allow volitional
      complete evacuation of urine and preserve renal function. Moreover, its structure
      has to be biocompatible, resistant to urinary encrustation and tolerant to
      bacterial infection. Various solutions have been proposed over the years to
      achieve these multiple requirements. However, most of these solutions and their
      corresponding prototypes did not advance beyond the stage of a preliminary report
      of experimental data. This review will bring out the 'proof of principal' in
      alloplastic prosthetic bladder, including type of alloplast and design concept
      and the recent development in tissue engineering approaches.

PMID- 10087387
TI  - Real indications for adrenalectomy in renal cell carcinoma.
AB  - OBJECTIVES: Adrenalectomy is a part of radical nephrectomy because of the
      surgical oncology principle of a 'wide margin beyond the malignancy' and due to
      concern over possible metastases to the ipsilateral adrenal gland, especially in
      upper pole tumors. But, neither the frequency, predisposing factors of the renal
      cell carcinoma nor mechanisms of involvement of the adrenal gland are well
      defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma
      to determine whether ipsilateral adrenalectomy during radical nephrectomy is
      essential. MATERIAL AND METHOD: In a series of 15,347 autopsies in Jena from 1985
      through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In
      the same period 9 adrenal metastases were found in 639 radical nephrectomies.
      Contralateral and bilateral metastases were seen in 15 cases of the autopsy
      series and in 2 cases of the operative series. RESULTS: The risk of adrenal
      metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic
      growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell
      carcinomas with adrenal metastases in the autopsy series, 23 had evidence of
      widespread disease and 22 had lymph node metastases. A preoperative abdominal
      computerized tomography was performed in all 9 patients of the operative series
      with renal cell carcinoma and adrenal involvement. The adrenal gland was
      considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the
      computerized tomography incorrectly interpreted as negative. CONCLUSION: We think
      adrenalectomy should only be performed if there is radiographic evidence of
      metastases in the adrenal gland or adrenal infiltration by a large upper-pole
      tumor is possible. Macroscopically normal adrenal glands should not be removed
      during tumor nephrectomy because the need and benefit of routine adrenalectomy
      are extremely limited.

PMID- 10087388
TI  - Association of health-related quality of life and benign prostatic enlargement.
AB  - OBJECTIVE: To investigate the association of benign prostatic enlargement and
      health-related quality of life (HRQoL) assessed by validated questionnaires.
      METHOD: Randomly selected men (n = 471) aged 40-79 years from Olmsted County,
      Minn. (USA) without prior prostate surgery or prostate cancer had a full urologic
      workup, including transrectal ultrasonography, in addition to completing
      questionnaires soliciting information about urinary symptom frequency, bother,
      degree of interference with daily activities and other measures of HRQoL.
      RESULTS: Disease-specific HRQoL was worse in older men, and men with more severe
      symptoms. Age-adjusted mean scores for symptom severity, bother and activity
      interference were about 50% worse for men with enlarged prostates (volume > 40
      cm3). After adjusting for age, men with enlarged prostates were nearly 3 times
      (95% CI 1.6, 5.1) as likely to have moderate to severe symptoms, and about twice
      as likely to have bother (odds ratio 2.4; 95% CI 1.3, 4.2) or activity
      interference (odds ratio 1.8; 95% CI 1. 0, 3.2) relative to men with smaller
      prostates. CONCLUSION: HRQoL measures are worse in men who are older and, after
      adjusting for age, in men with increased urinary symptom frequency and enlarged
      prostate. The broader spectrum of patients provided by the community-based random
      sampling allows elucidation of these important relationships.

PMID- 10087389
TI  - Laser prostatectomy. Long-term follow-up of 303 patients.
AB  - OBJECTIVE: This retrospective study was undertaken to evaluate results and
      complications in 303 patients with symptomatic bladder outlet obstruction due to
      benign prostatic hyperplasia (BPH) who underwent laser prostatectomy focusing on
      the long-term follow-up, 57 patients had a follow-up of more than 3 years.
      MATERIALS AND METHODS: A total of 303 patients were treated with the
      neodymium:YAG laser system for 1993 to 1997, of whom 57 patients were followed up
      for at least 3 years. All of the patients have been evaluated after 3 months, 6
      months and 2 years. 57 patients were evaluated after 3 years. Pre- and
      postoperative American Urological Association (AUA) symptom score, uroflowmetry
      (UF), and immediate and long-term complications were assessed. RESULTS: The mean
      AUA symptom scores of 303 patients decreased over the 24 months follow-up from
      16.9 to 7.6. In 57 patients after 36 months the mean AUA symptom score was 7.1.
      The mean maximal UF increased over the 24 months from 9 to 14.1 cm3/s in 303
      patients. In 57 patients at 3 years the mean UF was 13. 9 cm3/s. The overall
      complications of 303 patients included two perforations of the bladder wall and
      two perforations of the prostatic capsule. Six (1.9%) patients had postoperative
      febrile UTI and 28 (9.2%) patients had acute urinary retention after catheter
      removal. Early bleeding occurred in 3 (0.9%) patients, late bleeding in 8 (2.4%),
      4 (1.2%) had urethral stricture, and 1 had stricture of the bladder neck. The
      overall reoperation rate for symptomatic residual tissue was 1.9% (6 patients).
      CONCLUSION: Neodymium:YAG laser ablation of prostate represents an efficacious
      surgical intervention for symptomatic bladder outlet obstruction due to BPH with
      minimal associated morbidity.

PMID- 10087390
TI  - Value of ultrasound-guided systematic sextant biopsies in prostate tumor mapping.
AB  - OBJECTIVE: To determine the value of positive sextant biopsies in assessing the
      location of prostate tumors within radical prostatectomy specimens and to
      determine if prostate weight influences the results. METHODS: From 1988 to 1996,
      166 radical prostatectomies were performed for localized prostate cancer
      diagnosed by means of ultrasound-guided sextant biopsies. The location of the
      biopsies was compared with that of tumor tissue within the radical prostatectomy
      specimen. RESULTS: Of the 996 biopsies, 331 (33%) were positive. The
      correspondence between the location of the biopsies and that of tumor tissue in
      the surgical specimen was found to have a sensitivity of 39.4%, a specificity of
      81.5%, a positive predictive value of 83.3%, negative predictive value of 36.4%
      and an accuracy of 52%. For prostates weighing < and >/= 45 g, the sensitivity
      was 39.9 and 38.9%, the specificity was 88 and 77.2%, the positive predictive
      value was 90.8 and 76.1%, the negative predictive value was 34.9 and 39.8%, and
      the accuracy was 52 and 52%, respectively. CONCLUSION: Negative biopsies do not
      predict a lack of tumor tissue in the corresponding prostate site after radical
      prostatectomy, and had less value than positive biopsies for prognostic staging
      before radical prostatectomy. Results of sextant biopsies are more significant
      for prognosis before radical prostatectomy when positive. Prostate weight
      influences the interpretation of the results of sextant biopsies.

PMID- 10087391
TI  - Value of routine transition zone biopsies in patients undergoing ultrasound
      guided sextant biopsies for the first time.
AB  - OBJECTIVE: To analyze the efficacy of routine transition zone biopsies in
      patients undergoing ultrasound-guided sextant biopsies for the first time because
      of a suspicious digital rectal examination (DRE) or an elevated serum prostate
      specific antigen (PSA) level. PATIENTS AND METHODS: During sextant prostatic
      biopsy two additional transition zone biopsies were performed in 164 consecutive
      patients: in 98 because of a serum PSA of >4.0 ng/ml, and in 66 because of a
      suspicious DRE. RESULTS: The overall cancer detection rate was 46.9% (77/164). In
      28 patients (36.4%) cancer was only detected in the peripheral zone, in 2 (2.6%)
      only in the transition zone and in 47 (61%) in both zones. CONCLUSION: Routine
      transition zone biopsies performed at the time of a first sextant biopsy seem to
      have low efficacy.

PMID- 10087392
TI  - Diagnostic value of ten systematic TRUS-guided prostate biopsies.
AB  - OBJECTIVE: To evaluate the improvement in the rate of detection of prostate
      cancer using an extensive protocol involving ten transrectal biopsies. METHODS: A
      total of 162 patients submitted to transrectal ultrasound-guided biopsy for
      elevated prostate-specific antigen (PSA) and/or abnormality on digital rectal
      examination were studied consecutively and prospectively. Five biopsies were
      performed in each lobe: between the three standard biopsies on each side, two
      additional biopsy specimens were taken in the same plane and at the same 45
      degrees angle. RESULTS: The complication rate with the ten-biopsy protocol was
      1.85%. Prostate cancer was detected in 40.1% of the patients. In the overall
      series, the percentage of diagnostic improvement brought about by this ten-biopsy
      protocol was +3.1%. The percentage improvement was greatest (+4.9%) in patients
      with PSA </=10 ng/ml. CONCLUSION: Increasing the number of biopsy cores without
      altering the angle of biopsy and/or the zone sampled does not lead to a
      significant improvement in the detection of prostate cancer.

PMID- 10087393
TI  - Reconstruction of large soft tissue defects in the inguinal and suprapubic region
      using a variety of flaps.
AB  - OBJECTIVES: To review a variety of optional reconstructive procedures for the
      surgical management of extensive soft tissue defects after radically curative or
      palliative resection of tumors, scars or damaged tissue in the inguinal and
      suprapubic region. METHODS: Clinical experience with 24 pedicled or free flaps
      applied in 20 patients to cover extensive defects with exposed underlying
      structures are presented. The proper selection of flap was based on the
      individual requirements of each patient taking into consideration age, cause,
      size, shape and deepness of the defect, donor site morbidity, the patient's
      general condition and the situation of vascular supply of the adjacent regions.
      RESULTS: A high success rate with a moderate rate of only minor complications
      leads to a reasonably short hospital stay with a definitive defect cover. In the
      cases of palliation a distinct improvement in quality of survival could be
      achieved. CONCLUSIONS: After extensive or radical resection almost every defect
      may be sufficiently covered in a single stage. The inferior epigastric flap
      serves as the most versatile flap, but nevertheless appropriate selection of the
      reconstructive technique must be adapted considering the complexity of the
      illness and defect in each individual case.

PMID- 10087394
TI  - Reasons of dropout from short- and long-term self-injection therapy for
      impotence.
AB  - OBJECTIVE: To define the satisfaction rate and the dropout causes of
      intracavernous self-injection therapy in impotent patients. METHODS: A total of
      250 impotent patients treated with intracavernous injection of drugs from 1991 to
      1997 were mailed a questionnaire about their experience with this method. If the
      patient discontinued therapy, eight possible explanations for discontinuation
      were tested to identify reasons for terminating therapy (multiple choices were
      allowed). The causes of impotence were correlated with the rates of patients
      continuing or discontinuing therapy. RESULTS: 144 of 250 patients (57.6%)
      returned the questionnaire. Of the 106 non-responding patients, 50% could not be
      reached due to relocation. The patients were divided into three groups according
      to the duration of injection use. In group I, 35 of 144 patients (24%) did not
      continue therapy at home because either they felt it was unnatural (20%), they
      were dissatisfied (20%), or they experienced improvement of spontaneous erections
      (15%). In group II, 57 of 144 patients (40%) continued therapy at home and
      dropped out after a mean duration of 6.9 (range 0.5-48) months due to
      dissatisfaction (22%), cost reasons (20%), or insufficient erection for
      penetration (19.4%). In group III, 52 of 144 patients (36%) were continuing
      therapy with a mean follow-up period of 19.8 (range 2-72) months. The mean ages
      were not statistically different in the three groups. Also the aetiologies of
      impotence were similar: 35% psychogenic, 25% organic, and 40% mixed
      psychogenic/organic. Patients with psychogenic aetiology seem to continue therapy
      more frequently than others. CONCLUSIONS: The long-term follow-up revealed a high
      attrition rate of intracavernous self-injection therapy. Patient dissatisfaction,
      cost, and insufficient erection for penetration were the major causes of dropout.

PMID- 10087395
TI  - Conventional CT signs in staging transitional cell tumors of the upper urinary
      tract.
AB  - OBJECTIVES: To determine conventional computed tomography (CT) signs in the
      diagnosis and staging of upper urinary tract tumors (UUTTs). METHODS:
      Retrospective study was made of the CTs of 82 patients diagnosed with UUTTs. Nine
      CT signs were defined and compared with the pathology of the surgical specimen. A
      chi2 test was used for statistical analyses. RESULTS: We reviewed the CTs of 93
      UUTTs in 82 patients, of which 36% were invasive and 12% had positive lymph
      nodes. Renal parenchymal invasion was found in 82% of high-grade and in 18% of
      low-grade tumors (p = 0.001). 94% of the tumors with signs of renal parenchymal
      invasion were invasive (p < 0.001), as well as 88% of those appearing as renal
      masses (p = 0.005), with a global sensitivity of 64% and specificity of 97%. The
      CT sensitivity and specificity of detecting infiltration of the ureter was 67 and
      77%, respectively, and no sign was statistically significant. The detection of
      lymph node involvement had a sensitivity of 87.5% and a specificity of 98%.
      CONCLUSIONS: CT offers good sensitivity (87.5%) and specificity (98%) in the
      detection of lymph node involvement, and 64% sensitivity and 97% specificity for
      the detection of renal tumor invasion.

PMID- 10087396
TI  - Small cell carcinoma of the urinary bladder treated with chemotherapy and
      radiotherapy: results in five cases.
AB  - Small cell carcinoma of the bladder is a rare and highly aggressive tumor. We
      report our experience with 5 consecutive patients treated with systemic
      chemotherapy and adjuvant radiotherapy. TNM stages were T2N0M0 (1 patient),
      T3aN0M0 (3 patients) and T3bN1M0 (1 patient). The chemotherapy protocol was the
      one used with small cell lung cancer patients at our hospital: six cycles of
      alternating PE/CAV (PE: cisplatin, etoposide; CAV: cyclophosphamide, doxorubicin,
      vincristine). Cystoscopy was performed after the third cycle. Four out of 5
      patients were free of macroscopic disease. The fifth patient had persistent
      lesions and was treated by cystectomy. This patient developed a local-regional
      recurrence 4 months later and died shortly afterwards. Four patients completed
      the planned six cycles. Cystoscopy with bladder biopsy was then performed on
      each, and all had complete remission. They were treated with external
      radiotherapy (45 Gy pelvis, 60 Gy bladder). One patient had invasive bladder
      recurrence 12 months later and cystectomy was performed. At the last follow-up 42
      months later, he was alive and well. The other 3 patients were alive and free of
      disease 60, 48 and 27 months after diagnosis, respectively. These results are
      clearly more favorable than previous reports. Cystectomy might, therefore, be
      unnecessary in some patients.

PMID- 10087397
TI  - Estramustine reversal of resistance to intravesical epirubicin chemotherapy.
AB  - OBJECTIVE: Failure of epirubicin treatment of superficial bladder cancer implies
      multidrug resistance (MDR) which is common. MDR is characterised by decreased
      cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to
      both epirubicin and mitomycin C were used to investigate augmented therapy by
      adding the MDR reversing agent estramustine to an in vitro model. METHODS: Cells
      were cultured as monolayers. Fluorescence analysis was performed by flow
      cytometry and confocal microscopy. Cells were exposed to epirubicin 20 microg/ml
      for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under
      similar exposure conditions and MTT culture (dye reduction by live cells) allowed
      viable biomass to be read optically. RESULTS: Resistant cells accumulated eight
      times less epirubicin than sensitive cells. Confocal microscopy confirmed this
      for nuclear uptake. Accumulation in resistant cells can be increased to near
      sensitive cell levels using 40 microg/ml estramustine. Image analysis of confocal
      fluorescence showed a shift from cytoplasm to nucleus. This correlated with
      increased cytotoxicity. CONCLUSION: Estramustine plus epirubicin chemotherapy can
      overcome MDR and may achieve more successful tumour killing in vivo. It may also
      prevent emergence of resistance. Primary TCC culture examination permits
      detection of sensitive and resistant cells and may predict outcome allowing a
      more logical treatment selection.

PMID- 10087398
TI  - Congenital urine flow impairments of the upper urinary tract 

PMID- 10087399
TI  - Rheumatoid arthritis--a gene transfer disease.
AB  - Sera from patients with rheumatoid arthritis (RA) were from the very start
      instrumental in detecting and delineating the human immunoglobulin (Ig) allotypes
      in the Gm system. Knowledge that human Ig production is under Mendelian control
      and not determined by templates of antigen would not have come to the fore if it
      were not for RA patients. Worldwide experience shows that RA patients are prone
      to mount an immune response to human Ig allotypes. Major Gm allotypes are defined
      at the amino acid and nucleotide levels. Gene technology has been developed for
      defining these allotypes. Studies of the Gm allotypes and anti-Gms have led to
      two apparently paradoxical findings: (1) In conflict with Mendelian law, non
      nominal or hidden allotypes have been observed and recently documented at the DNA
      level. (2) In RA, an immune response to other individuals' Mendelian allotypes is
      prevalent, although RA is generally considered an autoimmune disease. These
      findings led us to conclude that RA is not initially an autoimmune disease but a
      gene transfer disease. A brief review of viral high-jacking and transfer of human
      genes is given along with reasons for considering the herpesvirus family in
      particular. Genes determining incompatible Ig allotypes are transferred. We have
      shown that these genes are expressed in RA synovia. Ig-anti-Ig complexes arise
      and may have arthritogenic potential, as observed in serum sickness.

PMID- 10087400
TI  - Nucleotide sequences specific for nonnominal immunoglobulin allotypes in
      rheumatoid arthritis patients and in normal individuals and their expression in
      synovial tissue of rheumatoid arthritis patients.
AB  - The production of antibodies against nonnominal immunoglobulin allotypes in
      rheumatoid arthritis (RA) patients suggests that the immune system of these
      patients has been exposed to such foreign allotypes. The presence of nonnominal
      allotypes is, however, a genetic enigma. We searched for nucleotide sequences
      specific for nonnominal G3mg and G3mb copies in individuals homozygous for these
      alleles. Using a sensitive and specific nested polymerase chain reaction (PCR)
      method with genomic DNA from blood of 18 RA patients and 5 normal controls, we
      found G3mg sequences in 18 of 18 tested G3mb homozygous persons. The allele
      specificity of the PCR fragments was confirmed by sequencing and RFLP analysis.
      The PCR products contained genomic nonspliced parts of the nonnominal sequences.
      An analysis of cDNA from inflammatory tissue of 5 RA patients detected nonnominal
      G3mb sequences in 1 of 3 tested G3mg homozygotes and G3mg sequences in 2 of 2
      tested G3mb homozygotes. The cDNA-derived PCR products contained sequences from
      normally spliced nonnominal Ig fragments. The results also showed that the
      nonnominal Ig sequences were present in very low copy numbers, lower than the
      Mendelian 1-2 copies per cell. The origin of such a low copy number of Ig gene
      fragments may be explained by a virus-mediated capture and transfer mechanism of
      Ig gene fragments generated by the normal Ig switch-associated gene excision
      process.

PMID- 10087402
TI  - A dinucleotide repeat polymorphism located in the IFN-alpha/beta gene cluster at
      chromosome 9p22 is not associated with multiple sclerosis in Sardinia.

PMID- 10087401
TI  - HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 polymorphism detected by PCR-SSP
      in a semi-urban HIV-positive Ugandan population.
AB  - PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The
      results represent a more comprehensive description of HLA in an African
      population than previously described and are in concordance with data from a
      general Black population. Substantial differences exist between this population
      and Caucasoid populations in which immunological responses to HIV have been
      investigated; this emphasises that the main HLA-restrictive elements for HIV
      specific cytotoxic T lymphocytes will most likely be different for each
      population.

PMID- 10087403
TI  - Genetic polymorphism of human complement factor I (C3b inactivator) in the
      Chinese Han population.
AB  - The human complement factor I (IF) polymorphism has been analysed by
      polyacrylamide gel isoelectric focusing electrophoresis of neuraminidase-treated
      EDTA plasma samples followed by immunoblotting and enzymatic detection. In a
      population study among 121 random individuals from Chengdu, PR China, three
      different common phenotypes were observed. The results show that IF is
      polymorphic in the Chinese population. The allele frequencies were as follows:
      FI*A = 0.153, FI*B = 0.847. The distribution of observed phenotypes was in
      accordance with the Hardy-Weinberg equilibrium. In comparison to other Asian
      population studies, the frequency of the IF*A allele was the highest in the
      Chinese population studied here.

PMID- 10087404
TI  - Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic
      subjects.
AB  - The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central
      role in driving the inflammatory immune responses which are present in atopic
      airway disease. This study examined the distribution of two putative IL-4
      promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe
      and moderate asthma, non-asthmatic atopy and control subjects. Neither
      polymorphism was identified in any of the samples tested. The data suggest that
      either the polymorphisms are present at very low frequencies or are artefacts of
      the B cell lines from which they were identified.

PMID- 10087405
TI  - The human immunoglobulin heavy variable genes.
AB  - 'Human Immunoglobulin Heavy Variable Genes', the fourth report of the 'IMGT Locus
      on Focus' section, comprises five tables entitled: (1) 'Number of human germline
      IGHV genes at 14q32.33 and potential repertoire'; (2) 'Human germline IGHV genes
      at 14q32.33'; (3) 'Human IGHV orphons on chromosome 15 (15q11.2)'; (4) 'Human
      IGHV orphons on chromosome 16 (16p11.2)', and (5) 'Human IGHV allele table'.
      These tables are available at the IMGT Marie-Paule page from IMGT, the
      international ImMunoGeneTics database (http://imgt.cnusc.fr:8104) created by
      Marie-Paule Lefranc, Universite Montpellier II, CNRS, France.

PMID- 10087406
TI  - Fertility potential of individual sperm donors.
AB  - OBJECTIVE: To study the fertility potential of individual semen donors with
      ejaculates of optimal as compared to suboptimal quality. METHODS: 363 semen
      donations were obtained from 11 donors between January 1993 and September 1997.
      270 samples were cryopreserved and 1,399 straws obtained from 120 ejaculates were
      used in 495 insemination cycles. RESULTS: 52 pregnancies were achieved in 128
      recipients (40.6%). No significant differences were found between donors of high
      fecundability and those of low fecundability regarding sperm parameters. The mean
      donor fecundability index was 10.5%. The optimal and suboptimal samples yielded
      similar results. Donors with suboptimal semen quality had an increased number of
      samples rejected after thawing. CONCLUSION: Traditional semen analysis parameters
      do not differentiate high from low fecundability donors. Suboptimal results of
      the semen analysis should not exclude potential donors from an artificial
      insemination donor (AID) program.

PMID- 10087407
TI  - Endometrial morphology and ultrasound vascular findings. A randomized trial after
      intramuscular and vaginal progesterone supplementation in IVF.
AB  - Luteal-phase supplementation has proved necessary in Gn-RH analog and human
      gonadotropin-stimulated cycles. We studied the effects of vaginally and
      intramuscularly delivered progesterone on the endometrium. Thirty patients
      enrolled in an IVF program without embryo transfer due to absence of
      fertilization were included in the study. Patients were randomly allocated to two
      treatment groups. Group A (n = 15) was administered 200 mg progesterone b.i.d. by
      the vaginal route (Esolut, Angelini) starting on the day of oocyte pick up and
      group B (n = 15) was given 100 mg intramuscular progesterone once daily
      (Prontogest, Amsa). Six days after HCG administration, biopsies were obtained for
      endometrial histological maturation and estrogen (ER) and progesterone (PR)
      receptor analyses. In addition, ultrasound measurements of endometrial thickness
      were made and uterine and myometrial artery flow was determined. Serum
      concentrations of estriol and progesterone were measured on the day of HCG, at
      oocyte pick up and at endometrial biopsy. The two treatment groups were similar
      in terms of follicular phase parameters during superovulation with Gn-RH analog
      and gonadotropin. Histologic, receptor and ultrasonographic analyses showed no
      significant differences between the two treatment groups. Our results indicate
      that both intramuscular and vaginal progesterone are equally effective on the
      endometrium.

PMID- 10087408
TI  - Emergency cervical cerclage: relation between its success, preoperative serum
      level of C-reactive protein and WBC count, and degree of cervical dilatation.
AB  - OBJECTIVE: To assess the relation between the preoperative serum level of C
      reactive protein (CRP) and the WBC count and the efficacy of emergency cervical
      cerclage. STUDY DESIGN: We retrospectively reviewed the medical records of 17
      women (16 singleton pregnancies and 1 twin pregnancy) who underwent emergency
      cervical cerclage (McDonald technique) between 21 and 26 weeks of gestation. The
      uterine cervix was dilated >/=3.0 cm and the intact (not ruptured) fetal
      membranes were visible or protruded into the vagina in all patients. The serum
      level of CRP and the WBC count were determined preoperatively and
      postoperatively. Emergency cervical cerclage was considered successful if
      delivery occurred >/=14 days after the procedure. RESULTS: Emergency cervical
      cerclage was successful in 12 women, including the woman with a twin pregnancy,
      but failed in 5 women. The preoperative serum level of CRP and the WBC count were
      significantly lower and dilatation of the cervix was significantly less in the
      success group than in the failure group. Cerclage was successful in all eight
      patients with cervical dilatation </=4.0 cm, but in only 4 of 9 patients with
      cervical dilatation >4.0 cm (p < 0. 05). Cerclage was successful in all 11 women
      with a preoperative serum level of CRP </=4.0 mg/dl and a WBC count </=14,000/
      microl compared with 1 of 6 women with either a CRP level >4.0 mg/dl or a WBC
      count >14,000/ microl (p < 0.01). CONCLUSION: A preoperative CRP value </=4.0
      mg/dl, a WBC count </=14,000/ microl, and cervical dilatation </=4.0 cm were
      significantly associated with prolongation of pregnancy after emergency cervical
      cerclage.

PMID- 10087409
TI  - Detection of small-for-gestational-age infants with poor perinatal outcomes using
      individualized growth assessment.
AB  - OBJECTIVE: Our objective was to evaluate individualized growth assessment using
      the Rossavik growth model for detection of small-for-gestational-age (SGA)
      infants with a poor perinatal outcome. METHODS: Rossavik growth models derived
      from second-trimester ultrasound measurements were used to predict birth
      characteristics of 47 singleton SGA infants. Individual fetal growth curve
      standards for head and abdominal circumference, and weight were determined from
      the data of two scans obtained before 25 weeks' menstrual age and separated by an
      interval of at least 5 weeks. Comparisons between actual and predicted birth
      characteristics were expressed by the Growth Potential Realization Index (GPRI)
      and Neonatal Growth Assessment Score (NGAS). The proportions of perinatal
      outcomes [mechanical delivery, low Apgar score, abnormal fetal heart rate (FHR)
      patterns, neonatal acidosis, meconium staining of amniotic fluid, neonatal
      intensive care unit (NICU) admission and maternal complications] were compared
      between SGA infants with normal NGAS and those with abnormal NGAS. RESULTS: Of
      the 47 fetuses studied, 27 had normal growth outcomes at birth and 20 showed
      evidence of intrauterine growth restriction, based on NGAS. There were
      significant increases in mechanical deliveries, abnormal FHR patterns and
      meconium staining of amniotic fluid in cases of growth-restricted neonates,
      determined using the NGAS classification, when compared with events related to
      normally grown infants. However, there were no significant differences in low
      Apgar score, neonatal acidosis, NICU admission and maternal complications between
      the 2 groups. CONCLUSION: Individualized growth assessment should be useful for
      detection of SGA infants with poor perinatal outcomes.

PMID- 10087410
TI  - Low myometrial glycogen content compared with rectus muscle in term pregnant
      women before labor.
AB  - Glycogen, glucose, some nucleosides and purine base derivatives were determined
      in biopsies from 10 term pregnant women undergoing elective cesarean sections
      before labor. The concentrations were compared in the biopsies which were cut
      from isthmus and fundus of the uterus and m. rectus abdominis. M. rectus biopsies
      had 1.5 and 2 times higher concentration of glycogen than the isthmic and fundal
      uterine biopsies, respectively. The glucose concentration in the striated muscle
      was on the other hand only half that in the myometrium. The uterus displayed
      regional differences in concentrations of glycogen (higher in isthmus). A
      relatively low glycogen content in term pregnant uterine smooth muscle compared
      with striated muscle signifies the restricted energy demands of pregnant
      myometrium.

PMID- 10087411
TI  - Fetal size as a determinant of obstetrical outcome of post-term pregnancy.
AB  - HYPOTHESIS: We hypothesized that there might be differences in the outcomes of
      post-term pregnancy according to fetal size. METHODS: A retrospective analysis of
      143 women with uncomplicated pregnancy that persisted beyond 42 weeks was
      conducted. Ultrasound dating was performed between 8 and 14 weeks in all cases.
      The obstetrical outcomes were compared between the cases in which neonatal birth
      weight was <3,600 g (non-large group) and >/= 3,600 g (large group). RESULTS: In
      primiparous women, there was no significant difference between the non-large and
      large groups in terms of the rate of cesarean section, but the rate of cesarean
      section for fetal distress in the non-large group was significantly higher than
      that found in the large group. In addition, the non-large group showed a
      significantly higher incidence of low pH (<7.20) compared with the large group
      (14/58 vs. 0/22, p < 0.01). In contrast, the rate of prolonged labor (>24 h) and
      induction failure in the non-large group were significantly lower than that in
      the large group. In multiparous women, there was no significant difference in
      obstetrical outcomes between the non-large and large groups. CONCLUSIONS:
      Primiparous women who were delivered of fetuses weighing not less than 3,600 g at
      post-term periods were at lower risk of fetal distress on the one hand and at
      higher risk of induction failure associated with infavorable cervix on the other.
      This study suggests that post-term pregnancy should be dealt with differently
      based on fetal weight.

PMID- 10087412
TI  - The staffs' views regarding young men involved in decisions on abortion:
      preliminary information from a study of outpatient clinics for adolescents in
      Sweden.
AB  - The purpose of this study was to obtain knowledge about the opportunities
      available to Swedish teenage boys and young men for obtaining advice and support
      during the process involved in making decisions on abortion. The study was
      carried out at Swedish Outpatient Clinics for Adolescents. We also wanted to
      obtain knowledge about the staffs' views of male attitudes and feelings regarding
      abortion. This knowledge is intended for use in developing models for advice and
      support in this difficult situation. A questionnaire focused on current
      management routines and staff experiences of questions and problems taken up by
      the male partner concerning abortion. Questionnaire answers indicated that the
      potential father, as well as the mother, requires active care and information
      together with the partner. There was also a need for individual support and
      information for male partners requiring engagement of health care professionals
      who are familiar with the problems involved.

PMID- 10087414
TI  - Influence of cigarette-smoking on the result of the triple test.
AB  - The aim was to establish whether the risk of trisomy 21 in women smokers
      undergoing triple test differs to women nonsmokers, whether increased smoking
      changes the hormonal values, and if the cessation of smoking at the beginning of
      pregnancy has any influence on the triple test. 1,854 pregnant women were
      interviewed regarding their smoking habits at the time of the triple test. They
      were divided into 5 groups: (a) nonsmokers; (b) smokers before pregnancy; (c) 1-5
      cigarettes; (d) 6-10; (e) 11 or more. MOM values of AFP, E3 and beta-HCG and Down
      risk calculated by the triple test were compared within the 5 groups. Increasing
      smoking was associated with a reduction in MOM values of beta-HCG. Smokers were
      significantly less likely to be counseled for karyotyping (cut-off level 1:250)
      than nonsmokers. The values of women who stopped smoking at the beginning of
      pregnancy were not different to nonsmokers. The results suggest the benefits of
      inclusion of smoking habits for the calculation of the triple test.

PMID- 10087413
TI  - 25 mg or 50 mg of oral methotrexate followed by vaginal misoprostol 7 days after
      for early abortion: a randomized trial.
AB  - BACKGROUND: Several combinations of oral or intravenous methotrexate plus vaginal
      misoprostol have been used for early abortion with success rates varying widely.
      So far, any study has evaluated the efficacy and safety of lower doses of oral
      methotrexate followed by vaginal misoprostol for early abortion. OBJECTIVES: To
      evaluate the efficacy and safety of methotrexate 25 or 50 mg orally and 800
      micrograms of misoprostol vaginally 7 days after the methotrexate for abortion at
      </=56 days of gestation. STUDY DESIGN: Three-hundred and ten pregnant women
      seeking elective abortion were randomly allocated to receive 25 mg (group I) or
      50 mg (group II) of methotrexate orally and 800 micrograms of misoprostol
      vaginally 7 days after the methotrexate. The misoprostol dose was repeated 48 and
      96 h later if the abortion did not occur. Outcome measures included successful
      abortion (complete abortion without requiring a surgical procedure), side effects
      and vaginal bleeding. Relative risks were used for the comparison between the
      outcomes from both treatment regimens. RESULTS: In group I aborted 135/148 cases
      (91%, 95% CI 85, 95%), and 139/154 cases (90%, 95% CI 84, 94%) aborted in group
      II (relative risk [RR] = 1.01, RR 95% CI 0.94, 1.09). CONCLUSIONS: The two
      treatment regimens showed the same efficacy and safety, so it would be advisable
      at least to use the smaller methotrexate dose, i.e. 25 mg.

PMID- 10087415
TI  - Patient's acceptance of outpatient hysteroscopy.
AB  - There is a trend towards performing hysteroscopy and endometrial biopsy on an
      outpatient basis, as this alleviates the need for both an inpatient stay and a
      general anesthesia. Despite the wide acceptance by medical staff, there are few
      publications on how patients actually tolerate and accept these procedures. We
      performed a survey on 185 patients attending the outpatient hysteroscopy clinic
      at a teaching hospital to assess the degree of pain and their acceptance to those
      procedures using a visual analogue scale. All procedures were successfully
      performed under no anesthesia without complications. The mean age of the patients
      was 48 (range 24-78) and 9.4% were nulliparas. The mean pain experienced was 4.7
      (SD 2.7) during hysteroscopy and 5.0 (SD 2.9) during endometrial biopsy. The
      overall preference scores for the procedure to be done under was 3.1 (SD 3.7).
      About 7% of patients expressed a preference for an overnight stay in hospital
      after the procedure, but the preference score was low (2.5, SD 3.6). The
      procedure was well accepted (8.3, SD 2.4) and highly recommended by the patients
      (8.4, SD 2.9). Outpatient hysteroscopy is well accepted and tolerated by
      patients.

PMID- 10087416
TI  - Effect of treatment with GnRH agonists on new markers of bone metabolism.
AB  - To assess the utility of new markers in monitoring bone turnover during treatment
      with GnRH agonists, alkaline phosphatase (total and bone specific) and urinary N
      telopeptides were measured. 16 women undergoing treatment with GnRH agonists for
      endometriosis or leiomyomas were studied before and 3 months after the onset of
      treatment. N-telopeptide levels increased significantly (44% of baseline, p <
      0.05). Bone specific alkaline phosphatase (BALP), measured with a new ELISA
      assay, was more elevated (40% of baseline, p = 0.001) than total ALP (15% of
      baseline, p < 0.001). In conclusion, in estrogen deficiency states, urinary N
      telopeptide measurements provide a quantitative measure of bone resoption. In the
      assessment of bone formation, BALP determination is move sensitive than total ALP
      and this may be clinically useful.

PMID- 10087417
TI  - Fibrogenesis in peritoneal endometriosis. A semi-quantitative analysis of type-I
      collagen.
AB  - OBJECTIVE: To evaluate the degree of fibrosis in the stroma of peritoneal
      endometriosis, according to the macroscopic appearance. METHODS: Red and black
      lesions of peritoneal endometriosis were collected and type-I collagen was
      immunohistochemically identified. The percentage of the stained area in the
      stroma was measured using a computerized image analysis system. RESULTS: There
      was a significant difference in the mean percentage of the total stained area
      between red and black lesions. CONCLUSION: The amount of type-I collagen is
      significantly higher in the stroma of black peritoneal lesions than in red
      peritoneal lesions.

PMID- 10087418
TI  - Transforming growth factor-alpha levels in the serum and ascites of patients with
      advanced epithelial ovarian cancer.
AB  - A variety of cytokines have been identified to play a role in ovarian cancer. In
      this pilot study, we sought to determine whether transforming growth factor-alpha
      (TGF-alpha) was detectable in the serum and ascites of women with advanced stage
      epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked
      immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment
      for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum
      levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The
      group with undetectable levels had a 6-month greater median survival; detectable
      TGF-alpha might be a negative prognostic indicator. In a separate group
      undergoing second-look laparotomy, differences in median TGF-alpha values versus
      controls and the primary study group approached significance. TGF-alpha was
      detected in significantly more control peritoneal fluid samples than in patient
      ascites. A larger study is warranted.

PMID- 10087419
TI  - Nucleolar organizer regions in differentiated preneoplastic and neoplastic
      endometrial lesions.
AB  - The aim of the study was the quantitative assessment of nucleolar organizer
      regions (NORs) in the cells of preneoplastic and neoplastic endometrial lesions.
      Retrospective analysis included tissue material obtained from 87 patients with
      simple and complex hyperplasia with or without atypia and well-differentiated
      stage-I endometrial adenocarcinoma. Sections were made from routine paraffin
      blocks and stained with AgNO3. The mean number of AgNORs per cell was determined.
      The results obtained indicate that the evaluation of proliferative activity of
      cells expressed by AgNOR count can help in the distinction between atypical
      hyperplasia and well-differentiated adenocarcinoma, and thus can serve as a
      useful pathological criterion.

PMID- 10087420
TI  - Calcium dobesilate lowers the blood pressure in mild to moderate midtrimester
      hypertension: a pilot study.
AB  - To test the effects of calcium dobesilate (Doxium) in pregnancies complicated
      with pregnancy-induced hypertension or mild/moderate pre-eclampsia a double
      blind, placebo-controlled pilot study was carried out. Primigravida patients
      (gestational age </=34 weeks) daily took 2 g Doxium or placebo until delivery.
      Twelve patients received placebo for 53 days, and 11 patients took the drug for
      57 days on average. At the start of the study 2 patients in the placebo group
      (PG) and 8 in the Doxium group (DG) had pre-eclampsia. The mean arterial pressure
      (mean +/- SD) significantly decreased from 118 +/- 7 to 99 +/- 9 mm Hg in the DG
      (p = 0.003), while in the PG it had slightly increased by the end of the study.
      Proteinuria was higher in the DG at the start but not at the end; however,
      significant changes of this parameter were detected in neither of the groups
      throughout the study. Fibronectin decreased significantly in both groups but it
      was more pronounced in the DG (23.8 vs. 9.4%). Changes of platelet count, plasma
      and blood viscosity, and erythrocyte deformability were favourable in the DG but
      in the PG these parameters had deteriorated although the alterations were not
      significant. No marked differences were found between the two groups regarding
      fetal well-being, courses of deliveries, and the neonatal period. Neither
      maternal nor fetal/neonatal side effects were noticed. It seems that Doxium
      favourably influences the blood pressure and consequently decreases the
      requirement for medication and hospitalisation in cases of mild to moderate
      midtrimester hypertension.

PMID- 10087421
TI  - Failure of high-dose chemotherapy with peripheral blood stem cell support for
      refractory placental site trophoblastic tumor.
AB  - Placental site trophoblastic tumor (PSTT) is a rare form of gestational
      trophoblastic disease. The metastatic and refractory cases have a very poor
      prognosis. To our knowledge, this is the first report of the application of high
      dose chemotherapy with autologous peripheral blood stem cell transplantation
      (PBSCT) for the treatment of refractory metastatic PSTT. A 36-year-old woman had
      a metastatic PSTT refractory to several lines of chemotherapy. She was treated
      with high dose of carboplatin and etoposide with autologous PBSCT. She showed
      only a temporary response to high-dose chemotherapy with PBSCT support and died
      of disease.

PMID- 10087422
TI  - Implantation versus infiltration: the Sampson versus the endometriotic disease
      theory.
AB  - It has been assumed that endometriosis is a progressive disease, with growth and
      development of lesions being inevitable once the disease has started. The
      implantation and the metaplasia theories describe the mechanism of initiation of
      endometriotic lesions, but do not explain the different clinical manifestations
      of endometriosis. To explain the variable expression, growth and development of
      lesions into severe disease, a new endometriotic disease theory is proposed. This
      theory suggests that progression of endometriosis to endometriotic disease is
      considered similar to the onset and progression of a benign tumour. In this
      theory, the most important factor in the development of endometriotic disease is
      not the initial implantation/metaplasia, but cellular changes such as mutations.
      According to this theory, endometriotic disease develops from endometriotic cells
      that have 'escaped' the influence of protective and regulatory factors in the
      peritoneal fluid.

PMID- 10087423
TI  - Intercellular adhesion molecule-1 and hepatocyte growth factor in human
      endometriosis: original investigation and a review of literature.
AB  - Defects in the cell-mediated immune system may play a role in the pathogenesis or
      progression of pelvic endometriosis. Possible mediators include macrophages,
      interleukins-1 and -6, and tumor necrosis factor-alpha. More recent work points
      to the involvement of adhesion molecules and growth factors. To clarify the
      pathogenesis of endometriosis, we compared the characteristics of soluble
      intercellular adhesion molecule-1 (soluble ICAM-1) and hepatocyte growth factor
      (HGF) in women with and without endometriosis. We found that, in patients with
      endometriosis, the concentrations of soluble ICAM-1 in peritoneal fluid increased
      and interfered with the activity of natural killer cells. We also found that HGF
      secretion was significantly increased in cultured endometrial stromal cells, and
      that HGF stimulated the proliferation and migration of, and morphogenic changes
      in, endometrial epithelial cells. HGF and ICAM-1 play important roles in the
      initiation and regulation of endometriotic lesions on the microenvironment level.
      The increased secretion of HGF by eutopic endometrial stromal cells may
      contribute to the pathogenesis of endometriosis, whereas the increased levels of
      soluble ICAM-1 may impair natural killer cell activity and accelerate the
      progression of the disease.

PMID- 10087424
TI  - Coelomic metaplasia theory of endometriosis: evidence from in vivo studies and an
      in vitro experimental model.
AB  - Ultrastructure studies of pelvic peritoneal tissue from women undergoing
      laparotomy suggest that before endometriosis has become established in the
      peritoneum, there might be a metaplastic change by peritoneal mesothelial cells
      into endometrial glandular cells. A new in vitro experimental model of
      endometriosis using human ovarian surface epithelium cells has shown evidence
      that endometriotic lesions can arise by a process of metaplasia from the ovarian
      surface epithelium. In this model, when both ovarian surface epithelium and
      ovarian stromal cells were cocultured with 17beta estradiol in a three
      dimensional collagen gel lattice, the ovarian surface epithelium cells formed a
      lumen structure, surrounded by endometrial stromal cells with an epithelial
      mesenchymal structure. Immunoreactivity for epithelial membrane antigen and
      cytokeratin was shown in the glandular cells and cilia, as well as in the
      microvilli. Electron microscopy showed evidence of tight junctions on cell
      surfaces. These findings suggest that endometriosis may manifest as a serial
      change from the adjacent mesothelial cells.

PMID- 10087425
TI  - Pathogenesis of endometriosis: the role of peritoneal fluid.
AB  - Peritoneal fluid is a specific microenvironment. It originates mainly as an
      ovarian exudation product due to increased vascular permeability, and contains
      large amounts of macrophages and their secretion products, which include growth
      factors, cytokines and angiogenic factors. Similarly, within the ovary, there is
      also a specific microenvironment, best characterised by the follicular milieu
      with steroid hormone concentrations that are 1,000 times higher than in plasma.
      Since endometrial cells in peritoneal fluid and superficially implanted cells
      will be influenced by peritoneal fluid concentrations, any differences found
      between minimal endometriosis and eutopic endometrium could be the consequence of
      their different local environments, rather than inherent cellular differences.
      Superficial endometrial implants may be regulated by factors in peritoneal fluid,
      while deep endometriosis and cystic ovarian endometriosis may be under the
      influence of factors in blood and within the ovary, in which case minimal
      endometriosis may be physiologic only, while deep endometriosis and cystic
      ovarian endometriosis, both associated with pelvic pain and infertility, may be a
      pathological state. In conclusion, the local endocrine environment, that is, in
      blood, peritoneal fluid, and within the ovary, should be taken into account to
      explain the differences between superficial, deep and cystic ovarian
      endometriosis, together with inherent differences in the endometrial cells of
      women with and without endometriosis.

PMID- 10087426
TI  - Role of cytokines in progression of endometriosis.
AB  - Peritoneal fluid in women with endometriosis contains an increased number of
      activated macrophages that secrete a variety of cytokines, including interleukin
      (IL)-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor-alpha
      (TNF-alpha). Cytokines may be involved in the control of implantation and the
      growth of endometrial cells outside the uterus. In addition, several cytokines
      have been implicated in or directly associated with angiogenic activity in
      endometriosis. There could be a relationship between the levels of cytokines in
      the peritoneal fluid of patients with endometriosis and the status of the lesions
      in such patients. Peritoneal endometriosis can be classified as having red,
      black, or white lesions. Red lesions are known to be an active form of early
      endometriosis, because vascularization and mitotic activity are shown to be most
      prominent in these lesions. We found that the peritoneal fluid levels of TNF
      alpha and IL-8 were significantly higher in patients with endometriosis, and
      correlated with the size and number of active lesions. In addition, TNF-alpha and
      IL-8 stimulated the growth of ectopic endometrial stromal cells. These cytokines
      with angiogenic activity may therefore have significant roles in the pathogenesis
      of endometriosis.

PMID- 10087427
TI  - Molecular analysis of clonality in ovarian endometrial cysts.
AB  - Ovarian endometrial cysts, one of the typical manifestations of endometriosis,
      are classified as tumor-like lesions rather than as neoplasms. Clonality analysis
      provides important information on the histogenesis and progression of neoplastic
      diseases. It is generally accepted that most neoplasms are monoclonal in origin,
      while the clonality of endometrial cysts remains uncertain. In our study, the
      clonality of endometrial cysts was analyzed by means of polymerase chain reaction
      (PCR) based on restriction fragment length polymorphism of the X chromosome
      linked human androgen receptor gene (HUMARA) and on random inactivation of the
      gene by methylation. We separated 21 fresh epithelial cell samples from 11
      endometrial cysts and found that all were monoclonal in the methylation pattern
      of the human androgen receptor alleles. Moreover, in each of the five cysts where
      epithelial cells were sampled from multiple areas, the methylation patterns of
      all samples from a single cyst were identical. These data indicate that
      endometrial cysts are monoclonal in origin and suggest their neoplastic
      potential.

PMID- 10087428
TI  - The physiopathology of endometriosis: pollution and dioxin.
AB  - Reports in the literature of an increasing incidence of endometriosis in
      industrialized countries and increasing problems with pollution in these
      countries leads to speculation about a possible link between one of the most
      harmful components of pollution, dioxin, and endometriosis. To establish this
      link, we need to examine three issues more closely: What are the effects of
      dioxin, what is the true incidence of endometriosis, and what is the nature of
      the association between endometriosis and dioxin. This report reviews current
      thinking on these issues.

PMID- 10087429
TI  - Low-dose vitamin K1 versus short-term with holding of acenocoumarol in the
      treatment of excessive anticoagulation episodes induced by acenocoumarol. A
      retrospective comparative study.
AB  - BACKGROUND: No consensus exists about the management of iatrogenically induced
      excessive hypocoagulability episodes. OBJECTIVE: To compare the two most common
      therapeutic approaches in such situations (discontinuation of the oral
      anticoagulant vs. low-dose subcutaneous vitamin K1) when acenocoumarol is the
      normally used anticoagulant. PATIENTS AND METHODS: The study was retrospective
      and comparative. Patients received antithrombotic therapy using acenocoumarol.
      Anticoagulant plasmatic activity was assessed through the international
      normalized ratio (INR) recorded from December 1994 to December 1997 at two
      medical centers. RESULTS: INR is brought faster to a safe range in patients
      treated with low-dose vitamin K1 (p = 0.01). Their long-term behavior is also
      more stable and predictable and no resistance to the oral anticoagulant was
      found. CONCLUSION: Low-dose vitamin K1 is a safer therapeutic option compared to
      simply withholding the oral anticoagulant. Its best scheme of administration,
      however, has yet to be defined.

PMID- 10087430
TI  - Randomized assessment of a warfarin nomogram for initial oral anticoagulation
      after venous thromboembolic disease.
AB  - Standard treatment for venous thromboembolism is parenteral heparin followed by
      warfarin. In this study we assess whether a standardized method of ordering
      warfarin reduces the duration of hospitalization. Consecutive patients were
      randomized to receive warfarin managed by attending physicians or by a nomogram.
      Patients were stratified according to primary or secondary venous
      thromboembolism. Prothrombin times were measured daily and heparin was given for
      a minimum of 5 days and stopped when the International Normalized Ratio was >1.9.
      Patients were followed for 3 months. There were 111 patients, 80 with primary and
      31 with secondary venous thromboembolism. Overall there were no differences
      between the two warfarin groups with respect to length of admission. Given the
      prolonged duration of admission in many patients with secondary venous
      thromboembolism, a subset analysis was conducted on the 80 patients with primary
      venous thromboembolism. Patients in the standard group stayed significantly
      longer than patients in the nomogram group (6.0 vs. 5.6 days, p = 0.02). The
      warfarin nomogram as tested is safe and leads to a significantly shorter length
      of stay for patients with primary venous thromboembolism as compared to standard
      practice.

PMID- 10087431
TI  - Early versus delayed introduction of oral vitamin K antagonists in combination
      with low-molecular-weight heparin in the treatment of deep vein thrombosis. a
      randomized clinical trial. The ANTENOX Study Group.
AB  - OBJECTIVE: To compare oral anticoagulant treatment (fluindione) started on either
      the 1st or the 10th day of a low-molecular-weight heparin (enoxaparin) treatment
      for deep vein thrombosis confirmed by venography. DESIGN: An open, multicenter,
      randomized study in two parallel treatment groups. INTERVENTIONS: All patients
      received enoxaparin, 1 mg/kg s.c. twice daily, and oral fluindione, 20 mg once
      daily, either beginning on day 1 or on day 10 of the enoxaparin treatment.
      Enoxaparin was discontinued once the international normalized ratio under
      fluindione was stable between 2.0 and 3.0 over 2 days. Fluindione treatment was
      maintained during a 3-month follow-up period. OUTCOME MEASUREMENTS: Specific
      examinations (venography and/or V/Q lung scanning and/or angiography) were
      performed only in the event of a clinically suspected recurrence of venous
      thromboembolism during the 3-month follow-up period. All cases were blindly
      assessed by an independent Reading Committee. RESULTS: A clinically suspected
      venous thromboembolism was confirmed by objective tests in 1 of 223 patients
      (group of delayed introduction of fluindione; n = 111). Equivalence was
      demonstrated between the two treatment schedules (p < 0.0001) for a maximal
      difference of 10% (90% confidence interval: -2.42 to 0.58). The mean duration of
      hospitalization was significantly reduced (p = 0.0001) in the group with early
      introduction of fluindione. The incidence of hemorrhage was comparable between
      the two treatment groups. CONCLUSION: Early and delayed introduction of oral
      anticoagulant treatment in association with subcutaneous enoxaparin in patients
      with deep vein thrombosis was shown to be equivalent in preventing the recurrence
      of venous thromboembolism. In patients with early introduction of oral
      anticoagulant, hospitalization was significantly reduced.

PMID- 10087432
TI  - Enoxaparin reduces cerebral edemaafter photothrombotic injury in the rat.
AB  - This study investigates the effect of enoxaparin (Lovenox, Klexane), a low
      molecular-weight heparin, on edema following a photothrombotic lesion using rose
      bengal dye in the rat. An area of cerebral ischemia was provoked in the right
      hemisphere of rats. Edema developed over 24 h after the lesion, as seen comparing
      water content of a core sample from the right hemisphere to that of a similar
      sample from the left hemisphere of each rat. Enoxaparin at 0. 5 mg/kg i.v. plus 2
      mg/kg s.c. reduced edema 24 h after lesion induction by 32% (p < 0.01) when the
      treatment was started 2 h after photothrombotic insult, with maintenance doses of
      2 mg/kg s.c. enoxaparin at 6 and 18 h. When the same initial treatment with
      enoxaparin was started 18 h after insult, there was still a significant reduction
      of 20% (p < 0.01) in cerebral edema. Administration of enoxaparin 18 h after
      insult reduced cerebral edema in a dose-dependent manner. There was no evidence
      of intracranial hemorrhages in any of the animal groups and when the hemoglobin
      content of the brain samples was assayed by the method of Drabkin, no increase in
      hemoglobin content was seen compared to sham-operated animals.

PMID- 10087433
TI  - Effects of polysulfonate derivative (GL 522-Y-1) on coagulation in vitro and
      thrombosis in vivo.
AB  - We have investigated the influence of a polysulfonate derivative - GL 522-Y-1 -
      on platelet-induced thrombin generation time, platelet adhesion to siliconized
      glass, platelet aggregation induced by collagen and ADP, on aPTT, PT and TT in
      vitro and studied its antithrombotic effect in an animal model of thrombosis in
      vivo. In vitro, GL 522-Y-1 caused inhibition of ADP- and collagen-induced
      aggregation. In a dose-dependent manner this compound inhibited PITT, aPTT, and
      PT. GL 522-Y-1 did not prolong thrombin time. GL 522-Y-1 inhibited in vivo the
      laser-induced thrombus formation after intravenous and oral administration. On
      the basis of its unique antithrombotic properties, GL 522-Y-1 seems to open a new
      pathway in the field of antithrombotics.

PMID- 10087434
TI  - Activated recombinant human coagulation factor VII therapy for intracranial
      hemorrhage in patients with hemophilia A or B with inhibitors. Results of the
      novoseven emergency-use program.
AB  - Activated recombinant human coagulation factor VII (rFVIIa) is a promising new
      therapeutic agent for patients with hemophilia A or B with inhibitors who
      experience serious bleeding episodes or who need coverage during surgical
      procedures. This open-label, uncontrolled, emergency-use study evaluated the
      efficacy and safety of rFVIIa in 11 hemophiliac patients and 1 FVII-deficient
      patient with life-threatening intracranial hemorrhage previously unresponsive to
      one or more alternative therapies. rFVIIa effectively controlled intracranial
      hemorrhage in 10 of the 12 patients. Patients with hemophilia A or B received an
      average of 96.9 rFVIIa injections over 14.7 days with a mean total administration
      of 153.3 mg, corresponding to 8.1 mg/kg. Most reported adverse events were
      considered to be unrelated to rFVIIa therapy. These findings suggest that rFVIIa
      is an effective and well-tolerated therapeutic option in the management of
      central nervous system bleeding in patients with hemophilia A or B with
      inhibitors.

PMID- 10087435
TI  - Increase in thrombin generation after coronary thrombolysis with rt-PA or
      streptokinase with simultaneous heparin versus heparin alone.
AB  - This study compares the extent of inhibition of thrombin generation and activity
      achieved in patients with acute myocardial infarction receiving fibrinolytic
      treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin
      treatment adjusted to the patients' weight with that achieved with the same
      heparin regimen but without fibrinolytic therapy. The study involved 90 patients,
      grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin
      without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin
      antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial
      thromboplastin time were measured. Patients treated with SK+heparin or rt
      PA+heparin and higher F1+2 plasma levels than the patients treated with heparin
      alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in
      that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were
      decreased in the three treatment groups at 24-48 h. There were no significant
      changes in TAT and FPA plasma levels among the three treatment groups at the
      different times. After thrombolytic therapy with both SK and rt-PA, there was an
      increase in thrombin generation, although high-dose intravenous heparin inhibited
      the different increases in thrombin associated with the thrombolytic agents to
      the same extent.

PMID- 10087436
TI  - Influence of HIV-infection on the Karnofsky score and general social functioning
      in patients with hemophilia.
AB  - Quality of live, defined by different models, has become a major focus of
      research in chronic disorders. Patients with hemophilia have been found to suffer
      seriously from the impact of HIV infection. To compare the impact of HIV
      infection on HIV-positive and HIV-negative patients, we evaluated a group of 60
      patients, 30 being positive and 30 negative, suffering from hemophilia, using the
      Karnofsky index of functioning besides more general social and clinical data.
      Most patients (n = 53) suffered from hemophilia A. The mean Karnofsky score
      decreased from 65.22 to 63.43 in the HIV-infected group between 1988 and 1991,
      but increased from 77.7 to 82.2 in the HIV-negative group; differences were not
      significant, though differences were significant between the HIV-infected and HIV
      negative groups. The Karnofsky score remained constant or increased in 26 (86.6%)
      of the HIV-negative patients, in contrast to 50% in the infected group. Seven
      patients, all from the infected group, had died in 1991. The initial Karnofsky
      score was not a prognosticator of survival. The group as a whole was socially
      well integrated. Consequently, the Karnofsky score can be a useful instrument in
      evaluating the global quality of live in HIV-infected patients, though a careful
      evaluation of results is necessary and a low initial score does not predict
      survival.

PMID- 10087437
TI  - Recent advances in understanding thyroid hormone receptor coregulators.
AB  - Thyroid hormones (L-triiodothyronine, T3; L-tetraiodothyronine, T4) regulate
      normal cellular growth and development, and general metabolism as well. Their
      various actions are mediated by the thyroid hormone receptor, a ligand-dependent
      transcriptional factor belonging to the nuclear hormone receptor superfamily. The
      recent discovery of coregulators (coactivators, corepressors, and cointegrators)
      has greatly enhanced our understanding of thyroid hormone receptor functions.
      Hence we review and discuss, in brief, the potential role of thyroid hormone
      receptor coregulators involved in diverse cellular activities.

PMID- 10087438
TI  - Trophic interactions between sensory nerves and their targets.
AB  - Neurotrophins are target-derived trophic factors essential for the survival and
      maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3
      (NT-3) are particularly important for sensory neurons. The actions of
      neurotrophins are through the p75 low-affinity receptor and the high-affinity
      receptor tyrosine kinase (trk). Each neurotrophin has its preferred receptor,
      i.e. trkA for NGF, and trkC for NT-3. The primary sensory neurons in the dorsal
      root ganglion are classified into two categories, namely, the large and small
      sensory neurons based on their size. The large sensory neurons with the
      expression of trkC depend on NT-3 for development and subserve the function of
      position sensations. Some of the small sensory neurons express trkA and are NGF
      dependent. They are responsible for nociceptive sensation, the detection of
      painful and thermal stimuli. A more intriguing observation is the bidirectional
      interactions between nociceptive nerves and their target, the skin. The
      peripheral processes of small sensory neurons innervate the epidermis of the skin
      as 'free nerve endings'. In denervated skin, there is a drastic reduction in the
      epidermal thickness, a finding corroborated by the phenomenon of trophic change,
      the shining and thinning of the skin, in the disorders of peripheral nerves. The
      performance of animals with peripheral nerve disorders improved after
      administration of neurotrophic factors. Based on these results, the therapeutic
      potentials of neurotrophic factors in human are under investigation.

PMID- 10087439
TI  - Anticonvulsants for soman-induced seizure activity.
AB  - This report describes studies of anticonvulsants for the organophosphorus (OP)
      nerve agent soman: a basic research effort to understand how different
      pharmacological classes of compounds influence the expression of seizure produced
      by soman in rats, and a drug screening effort to determine whether clinically
      useful antiepileptics can modulate soman-induced seizures in rats.
      Electroencephalographic (EEG) recordings were used in these studies. Basic
      studies were conducted in rats pretreated with HI-6 and challenged with 1.6 x
      LD50 soman. Antimuscarinic compounds were extremely effective in blocking
      (pretreatment) or terminating soman seizures when given 5 min after seizure
      onset. However, significantly higher doses were required when treatment was
      delayed for more than 10 min, and some antimuscarinic compounds lost
      anticonvulsant efficacy when treatment was delayed for more than 40 min. Diazepam
      blocked seizure onset, yet seizures could recur after an initial period of
      anticonvulsant effect at doses </=2.5 mg/kg. Diazepam could terminate ongoing
      seizures when given 5 min after seizure onset, but doses up to 20 mg/kg were
      ineffective when treatment was delayed for 40 min. The GABA uptake inhibitor,
      tiagabine, was ineffective in blocking or terminating soman motor convulsions or
      seizures. The glutamate receptor antagonists, NBQX, GYKI 52466, and memantine,
      had weak or minimal antiseizure activity, even at doses that virtually eliminated
      signs of motor convulsions. The antinicotinic, mecamylamine, was ineffective in
      blocking or stopping seizure activity. Pretreatment with a narrow range of doses
      of alpha2-adrenergic agonist, clonidine, produced variable protection (40-60%)
      against seizure onset; treatment after seizure onset with clonidine was not
      effective. Screening studies in rats, using HI-6 pretreatment, showed that
      benzodiazepines (diazepam, midazolam and lorazepam) were quite effective when
      given 5 min after seizure onset, but lost their efficacy when given 40 min after
      onset. The barbiturate, pentobarbital, was modestly effective in terminating
      seizures when given 5 or 40 min after seizure onset, while other clinically
      effective antiepileptic drugs, trimethadione and valproic acid, were only
      slightly effective when given 5 min after onset. In contrast, phenytoin,
      carbamazepine, ethosuximide, magnesium sulfate, lamotrigine, primidone,
      felbamate, acetazolamide, and ketamine were ineffective.

PMID- 10087440
TI  - Activation of muscarinic receptors in porcine airway smooth muscle elicits a
      transient increase in phospholipase D activity.
AB  - Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of
      phosphatidylcholine to produce phosphatidic acid and choline. In the presence of
      ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a
      unique characteristic of this enzyme. Muscarinic receptor-induced changes in the
      activity of PLD were investigated in porcine tracheal smooth muscle by measuring
      the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol
      ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The
      cholinergic receptor agonist acetylcholine (Ach) significantly but transiently
      increased formation of both [3H]PA and [3H]PEth in a concentration-dependent
      manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when
      pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD
      activity was inhibited by atropine (10(-6) M), indicating that activation of PLD
      occurred via muscarinic receptors. Activation of protein kinase C (PKC) by
      phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively
      blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8)
      to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but
      incompletely, inhibited by both GFX and calphostin C. From the present data, we
      conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor
      induced PLD activation is transient in nature and coupled to these receptors via
      PKC. However, PKC activation is not solely responsible for Ach-induced activation
      of PLD in porcine tracheal smooth muscle.

PMID- 10087441
TI  - Amino acid conservation and clinical severity of human glucose-6-phosphate
      dehydrogenase mutations.
AB  - More than a hundred naturally occurring mutations of human glucose-6-phosphate
      dehydrogenase (G6PD) have been identified at the amino acid level. The abundance
      of distinct mutation sites and their clinical manifestations make this enzyme
      ideal for structure-function analysis studies. We present here a sequence and
      structure combined analysis by which the severity of clinical symptoms resulting
      from point mutations of this enzyme is correlated with quantified degrees of
      amino acid conservation within 23 G6PD sequences from different organisms. Our
      analysis verifies, on a quantitative basis, a widely held notion that clinically
      severer mutations of G6PD usually occur at conserved amino acids. However, marked
      exceptions to this general trend exist which are most notably revealed by a
      number of mutations associated with chronic nonspherocytic hemolytic anemia
      (class I variants). When mapped onto a homology-derived structural model of human
      G6PD, these class I mutational sites of low amino acid conservation appear to
      localize in two spatially distinct clusters, both of which are populated with
      mutations consisting mainly of clinically severer variants (i.e. class I and
      class II). These results of computer-assisted analyses contribute to a further
      understanding of the structure-function relationships of human G6PD deficiency.

PMID- 10087442
TI  - Isolation of full-length cDNA and chromosomal localization of human NF-kappaB
      modulator NEMO to Xq28.
AB  - NEMO is an essential component of the IkappaB kinase complex. Others have shown
      that expression of mouse NEMO can complement the lack of responsiveness to NF
      kappaB stimuli in two NEMO-deficient cell lines. Here we report the isolation of
      a full-length human NEMO cDNA. Virtual translation of human NEMO cDNA predicts a
      48-kD coiled-coil protein which shares 87.9% identity and 90.5% similarity with
      the mouse homolog. By sequence alignment, we mapped the human NEMO gene to
      chromosome Xq28. We note that the NEMO and the G6PD (glucose-6-phosphate
      dehydrogenase) loci are arranged in a head-to-head orientation separated by no
      more than 800 bp. This map location is further supported by the sequence of an
      alternatively spliced variant of human NEMO mRNA. Thus, human NEMO is an X-linked
      gene closely adjacent to the G6PD locus.

PMID- 10087443
TI  - The fidelity of reverse transcription differs in reactions primed with RNA versus
      DNA primers.
AB  - Reverse transcriptase enzymes (RT) convert single-stranded retroviral RNA genomes
      into double-stranded DNA. The RT enzyme can use both RNA and DNA primers, the
      former being used exclusively during initiation of minus- and plus-strand
      synthesis. Initiation of minus-strand DNA synthesis occurs by extension of a tRNA
      primer that is associated with the viral genome, and plus-strand DNA synthesis is
      initiated from an RNase H- resistant polypurine tract of the genomic RNA that
      remains bound to the newly synthesized minus-strand DNA. All other phases of
      reverse transcription represent elongation of a DNA primer. We demonstrate that
      the polymerase fidelity of RT enzymes is significantly higher in tRNA-primed
      reverse transcription compared with DNA-primed reactions. Two mechanistic
      explanations can be proposed. First, the type of template-primer (T- P) duplex
      (RNA-RNA versus RNA-DNA) may affect the RT enzyme conformation such that the
      discrimination against incorrect nucleotides is affected. Second, the tRNA primer
      may act as a fidelity co-factor through specific association with the RT enzyme.
      According to the latter hypothesis, the increased fidelity observed for an RNA
      RNA T-P should persist at a distance from the initiation site, where the enzyme
      bound nucleic acid duplex will consist of RNA-cDNA. However, we measured that the
      effect of tRNA on the fidelity is detectable only at a short distance from the
      initiation site. These results indicate that the type of T-P duplex influences
      the fidelity of reverse transcription, suggesting that two small segments of the
      viral genome downstream of the initiation sites for minus- and plus-strand DNA
      synthesis are copied with a fidelity that is greater than average.

PMID- 10087444
TI  - Studies on the mechanisms responsible for inhibition of experimental metastasis
      of B16-F10 murine melanoma by pentoxifylline.
AB  - Pentoxifylline (PTX), a methylxanthine derivative widely used as a
      hemorheological agent in the treatment of peripheral vascular disease, was
      studied to unveil the mechanisms responsible for its inhibitory action on B16-F10
      experimental metastasis. In vitro pretreatment of B16-F10 cells with noncytotoxic
      concentrations of PTX significantly inhibited their adhesion to reconstituted
      basement membrane Matrigel(R) and type IV collagen as well as the relative
      activity of secreted 92 kD metalloproteinase. However, PTX pretreatment of B16
      F10 cells did not affect their in vitro invasiveness. Heterotypic organ adhesion
      assays carried out with B16-F10 cells and suspended organ tissues demonstrated
      that pretreatment with noncytotoxic concentrations of PTX of both, tumor cells or
      lung tissue, brought about a dose-dependent inhibition of melanoma cell adhesion
      to lung. Immunohistochemical studies using antibodies against CD31 adhesion
      molecule (PECAM-1) revealed that B16-F10 cells adhere to lung endothelial cells.
      Our results suggest that PTX may exert its inhibitory effect on tumor lodgment,
      and as a consequence of that on experimental metastases, through an inhibitory
      action on cell adhesion molecules.

PMID- 10087445
TI  - Antitumor effects of IL-6 on murine liver tumor cells in vivo.
AB  - IL-6 is a pleiotropic cytokine that is capable of modulating the diverse
      functions of hepatocytes such as acute phase responses and inflammation in the
      liver. To learn its antitumor effects in vivo, the cDNA of IL-6 was transfected
      into murine liver cells, TIB cells. IL-6-transfected TIB cells (TIB73-IL-6 or
      TIB75-IL-6) produced much higher levels of IL-6 compared with vector-transfected
      TIB cells (TIB73-vec or TIB75-vec). To investigate the effects of IL-6 on TIB
      tumor growth in vivo, IL-6-transfected TIB cells or vector-transfected TIB cells
      were injected subcutaneously into syngeneic mice. Vector-transfected TIB cells
      grew rapidly 3 weeks after injection, but IL-6-transfected TIB cells did not grow
      at all for up to 6 weeks. Pathologically, IL-6-transfected TIB cells demonstrated
      a severe necrosis and apoptotic pattern. Taken together, these results indicate
      that IL-6 functions as a growth inhibiting factor in vivo, and another biological
      role of IL-6 in the liver is suggested.

PMID- 10087446
TI  - Effects of leptin on melanin-concentrating hormone expression in the brain of
      lean and obese Lep(ob)/Lep(ob) mice.
AB  - The effect of leptin on the expression of melanin-concentrating hormone (MCH) was
      investigated in lean and genetically obese Lepob/Lepob mice. Murine leptin was
      subcutaneously infused using osmotic minipumps. The treatment period extended to
      7 days and the daily dose of leptin delivered was 100 microgram/kg of body
      weight. In situ hybridization was used to assess the effects of leptin infusion
      on the expression of MCH mRNA. MCH levels in the brain (hypothalamus/thalamus and
      the remaining part), spleen and testis were measured by radioimmunoassay coupled
      to HPLC of selected tissue extracts. Leptin significantly reduced final body
      weight, weight of brown adipose tissue, daily food intake in obese mice but not
      in lean animals. In obese mice, leptin led to a rapid reduction in food intake
      which reached statistical significance after only 24 h and which led to a
      significant reduction in the body weight after 3 days of treatment. Leptin
      restored the normal circulating levels of glucose and insulin in obese mice. The
      present results mainly provide evidence for a stimulating effect of leptin
      infusion on the MCH neuronal system. The hypothalamic/thalamic levels of MCH mRNA
      and peptide were higher in mice treated with leptin than in mice infused with
      phosphate-buffered saline. The stimulation of MCH neurons appeared particularly
      intense in obese mice, in which the effects of leptin infusion led to the
      reduction in MCH content of neuron fibers and terminals. Leptin did not affect
      spleen and testis MCH contents. In the light of the acknowledged orexigenic
      effects of MCH, the results of this study questioned the direct role of MCH in
      the action of leptin on energy balance. The increase in MCH expression following
      leptin could occur as a mechanism to compensate the decrease in energy deposition
      led to by leptin. It may also indicate that MCH mediates the metabolic actions of
      leptin indirectly or else that leptin influences actions of MCH other than those
      related to the regulation of energy balance.

PMID- 10087447
TI  - Serum leptin and regional cerebral blood flow during exposure to food in obese
      and normal-weight women.
AB  - Leptin is an adipocyte-derived product of the ob gene thought to be involved in
      the regulation of eating. Receptors for leptin have been found in multiple
      regions in the brain. In particular, hypothalamic receptors seem to be of
      fundamental importance for the biological effects of leptin. However, the
      association of leptin with cerebral function in humans has not been studied.
      Therefore, in order to assess the possible functional relationships between
      leptin and cerebral activity in humans, simultaneous serum leptin and regional
      cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3
      39.1) kg/m2] and 12 normal-weight [BMI 22.2 (20.3-24.6) kg/m2] women during
      exposure to food. The rCBF measurements were performed by 99mTc-ethyl-cysteine
      dimer single photon emission computed tomography. A strong inverse association
      was observed between the leptin and rCBF of hypothalamus during the exposure to
      food in the obese (r = -0.73, p = 0.02, n = 10), but not in the normal-weight
      subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of
      leptin with cerebral activity could be different in obese and normal-weight
      women; depressed activity of hypothalamic neurones in response to the high
      peripheral leptin concentration could be postulated to occur in obese women
      during exposure to food.

PMID- 10087448
TI  - Intracerebroventricular administration of bromocriptine ameliorates the insulin
      resistant/glucose-intolerant state in hamsters.
AB  - Bromocriptine, a potent dopamine D2 receptor agonist, suppresses lipogenesis and
      improves glucose intolerance and insulin resistance. Recent evidence suggests
      that bromocriptine may produce these effects by altering central nervous system
      (CNS) regulation of metabolism. To determine whether or not the CNS plays a
      critical role in these bromocriptine-mediated effects on peripheral metabolism,
      we compared the metabolic responses to bromocriptine when administered
      peripherally versus centrally in naturally obese and glucose intolerant Syrian
      hamsters. Male hamsters (BW 194 +/- 5 g) were treated with bromocriptine or
      vehicle either intraperitoneally (i.p., 800 microgram/animal) or
      intracerebroventricularly (i.c.v., 1 microgram/animal) daily at 1 h after light
      onset for 14 days while held on 14-hour daily photoperiods. Glucose tolerance
      tests (GTTs, 3 g glucose/kg BW) were conducted after treatment. Compared to
      control animals, bromocriptine i.p. significantly reduced weight gain (11.7 vs. 
      2.4 g) and the areas under the glucose and insulin GTT curves by 29 and 48%,
      respectively. Similarly, compared with vehicle-treated controls, bromocriptine
      i.c.v. at 1 microgram/animal substantially reduced weight gain (8.7 vs. -6.3 g),
      the areas under the glucose and insulin GTT curves by 31 and 44% respectively,
      and the basal plasma insulin concentration by 41% (p < 0.05). Furthermore, both
      treatments significantly improved insulin-mediated suppression of hepatic glucose
      production during a hyperinsulinemic-euglycemic clamp. Thus, daily administration
      of bromocriptine at a very low dose i.c.v. replicates the metabolic effects of
      bromocriptine administered i.p. at a much higher dose. This finding demonstrates
      for the first time that the CNS is a critical target of bromocriptine's metabolic
      effects.

PMID- 10087449
TI  - Effects of centrally administered pituitary adenylate cyclase-activating
      polypeptide on c-fos gene expression and heteronuclear RNA for vasopressin in rat
      paraventricular and supraoptic nuclei.
AB  - The effects of intracerebroventricular (i.c.v.) administration of pituitary
      adenylate cyclase-activating polypeptide (PACAP) on the expression of c-fos gene
      as well as heteronuclear (hn) RNA for arginine vasopressin (AVP) in
      paraventricular (PVN) and supraoptic nuclei (SON) of rats were investigated by
      immunohistochemistry for c-fos protein (Fos) and in situ hybridization
      histochemistry for c-fos mRNA and AVP hnRNA. The i.c.v. administration of PACAP
      (200 pmol/rat) caused a marked induction of Fos-like immunoreactivity (LI) in PVN
      and SON. The nuclear Fos-LI existed in AVP-LI containing cells in the PVN and
      SON. The expression of the c-fos gene in the PVN and SON was increased in a dose
      related manner 30 min after i.c. v. administration of PACAP. PACAP-induced
      expression of the c-fos gene was significantly reduced by pretreatment with a
      PACAP receptor antagonist, PACAP-(6-38)-NH2. In addition, Fos-LI and the
      expression of the c-fos gene were also observed in the periventricular region of
      the third ventricle after i.c.v. administration of PACAP. The induction of c-fos
      gene expression in the PVN and SON reached a maximum 30 min after PACAP
      administration. The expression of c-fos gene in the PVN and SON induced by i.c.v.
      administration of vasoactive intestinal peptide (200 pmol/rat) was weaker than
      that induced by PACAP. The hnRNA for AVP in the PVN and SON was significantly
      increased 30 min after i.c.v. administration of PACAP (200 pmol/rat). Our results
      suggest that PACAP activates PVN and SON neurons via PACAP receptors and, in
      parallel, transcription of the AVP gene in the PVN and SON.

PMID- 10087450
TI  - Site-specific induction of Fos immunoreactivity in preoptic and hypothalamic
      NADPH-positive neurons during glucoprivation.
AB  - Neuronal nitric oxide synthase, e.g. NADPH diaphorase (NADPH-d), catalyzes
      formation of the free radical, nitric oxide (NO), and occurs within brain
      structures that have functional significance for energy fuel homeostasis. The
      following studies examined whether populations of NADPH-d-positive neurons in the
      hypothalamus and nearby preoptic area express immunoreactivity for the nuclear
      transcription factor, Fos, in response to glucose substrate imbalance. Eight days
      after bilateral ovariectomy (OVX) and subcutaneous implantation of silastic
      capsules containing 30 microgram estradiol benzoate/ml, female rats were injected
      i.p. with the glucose antimetabolite, 2-deoxy-D-glucose (2DG; 400 mg/kg), or the
      vehicle, saline. The animals were sacrificed by transcardial perfusion 2 h after
      these treatments. Sections at 150-micrometer intervals throughout preoptic area
      and anterior and tuberal regions of the hypothalamus were processed for dual
      cytoplasmic NADPH-d enzyme activity and nuclear Fos-immunoreactivity (-ir). The
      glucose antimetabolite elicited expression of nuclear Fos-ir by NADPH-d-positive
      neurons in several neural structures, including the medial preoptic area, median
      preoptic nucleus, anterior commissural, periventricular magnocellular supraoptic
      nucleus, paraventricular nucleus, and medial part of the bed nucleus of the stria
      terminalis. In contrast, the extensive populations of NADPH-d-positive neurons in
      the ventromedial hypothalamic nucleus and lateral hypothalamic area showed very
      little immunolabeling for Fos in response to glucoprivation. This demonstration
      of nuclear immunoreactivity for Fos suggests that cellular glucopenia elicits the
      transcriptional activation, via AP-1 regulatory sites, of multiple populations of
      hypothalamic neurons characterized by the functional capacity to generate NO, and
      thus that this gaseous neurotransmitter may fulfill a role(s) in central neural
      mechanisms governing regulation of compensatory motor responses to metabolic
      imbalance.

PMID- 10087451
TI  - Differential gene expression response to gonadal hormones by preoptic regulatory
      factors-1 and -2 in the female rat brain.
AB  - Steroids and neuropeptides interact in the central nervous system (CNS) to
      regulate reproductive function and behavior. The preoptic regulatory factors,
      PORF-1 and PORF-2, are unique neuropeptides for which roles in gender-related
      brain development and function have been proposed. PORF-1 and PORF-2 expression
      in rat brain are age, region and gender dependent, and castration or
      hypophysectomy alter the metabolism of the PORF-1 and PORF-2 mRNAs in male rat
      brain and testes. If these two peptides have a role in gender-dependent brain
      function, then gonadal steroids might well affect their expression. The present
      study was designed to investigate the response of the PORF-1 and PORF-2 mRNAs to
      sex steroids in the female rat brain and to compare this response to that of two
      peptides whose roles in the neuroendocrinology of reproduction are well
      established, gonadotropin-releasing hormone (GnRH) and neuropeptide Y (NPY). Rats
      were ovariectomized and treated with placebo, estradiol (E2), progesterone (P4)
      or a combination of the two (E2/P4) and NPY, PORF-2, GnRH and PORF-1 mRNAs were
      quantified by nuclease protection assays. PORF-1, PORF-2 and GnRH mRNAs were also
      measured in intact rats during estrus and proestrus. Responses were compared in
      the preoptic anterior hypothalamus (POA), medial basal hypothalamus (MBH),
      cerebral cortex (CC) and hippocampus (HIPP). Expression of PORF-1 and PORF-2 was
      also confirmed in the female rat hypothalamus by in situ hybridization analysis.
      PORF-1 and PORF-2 mRNAs were detected in the adult female rat brain by both in
      situ hybridization and ribonuclease protection analyses. In situ hybridization
      analysis demonstrated that PORF-1 and PORF-2 mRNAs are expressed in hypothalamic
      neurons. RNase protection analysis showed that PORF-1, PORF-2 and NPY mRNAs were
      present in all four brain regions examined while GnRH expression was detected
      only in the MBH and POA. Estradiol alone upregulated expression of the PORF-1 and
      PORF-2 mRNAs in the ovariectomized rat in the POA and HIPP, and of NPY mRNA in
      the MBH and HIPP. Progesterone alone had a stimulatory effect on NPY mRNA in the
      MBH and HIPP. Treatment with a combination of E2/P4 downregulated PORF-2 mRNA in
      the POA as well as PORF-1, PORF-2 and NPY mRNAs in the CC. In contrast, E2/P4
      upregulated the PORF-2 and NPY mRNAs in the HIPP and NPY mRNA in the MBH. In the
      cycling rat, PORF-1 mRNA levels were higher during proestrus than estrus in both
      the MBH and POA, while PORF-2 mRNA levels did not change. In contrast GnRH mRNA
      was lower in the POA and higher in the MBH during proestrus compared with estrus.
      Thus, intrinsic factors, most likely both ovarian and neuroendocrine, regulate
      PORF-1 and GnRH expression in the intact cycling rat CNS in a region-dependent
      manner. In the ovariectomized rat, PORF-1, PORF-2, NPY and GnRH mRNAs all respond
      in a region-specific manner to sex steroid treatment. These data support the role
      of PORF-1 and PORF-2 in gender-dependent brain function in the adult female rat.

PMID- 10087452
TI  - Long-term changes in gastrin, cholecystokinin and insulin in response to oxytocin
      treatment.
AB  - The present study was designed to investigate how repeated injections of oxytocin
      influence plasma levels of vagally controlled hormones such as gastrin,
      cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous
      oxytocin and glucose. Since oxytocin may enhance the activity of centrally
      located alpha2-adrenoreceptors, a second aim of this study was to explore whether
      these receptors are involved in the effects. For this purpose, oxytocin (1.0
      mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male
      rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was
      collected and hormone levels were radioimmunoassayed. The oxytocin treatment
      caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and
      10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA;
      p < 0.01). In addition, both insulin and CCK levels were decreased in response to
      the oxytocin treatment when measured 3 and 10 days after the last injection
      (ANOVA; insulin p < 0.01, CCK p < 0.05). When the alpha2-adrenoreceptor agonist
      clonidine (2.5 microgram/kg intracerebroventricularly) was administered 3 days
      after the 5-day treatment period with oxytocin or saline, plasma levels of
      insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats,
      when compared to saline-treated controls receiving clonidine only. No change in
      glucose or somatostatin levels was found in response to the oxytocin treatment.
      In conclusion, these results show that oxytocin induces long-lasting changes in
      plasma levels of gastrin, CCK and insulin, without affecting somatostatin or
      glucose levels. These effects may be mediated by changes in vagal nerve activity.

PMID- 10087453
TI  - Inhibition of hormonally induced inositol trisphosphate production in Transfected
      GH4</ sup>C1 cells: A novel role for the D5 subtype of the dopamine receptor.
AB  - We have previously found that the D5 dopamine receptor couples to a G-protein
      other than Gsalpha, and could be involved in signaling pathways other than
      regulation of adenylyl cyclase. To describe interactions of the D5 receptor with
      cellular effectors, we used GH4C1 cells transfected with cDNA for the human D5
      receptor. Thyrotropin-releasing hormone (TRH, 100 nM) stimulated accumulation of
      inositol phosphates (IPs) fivefold in D5GH4C1 cells. Dopamine (DA, 10 microM)
      inhibited TRH-stimulated IP values by 29%; at higher concentrations (100 microM),
      maximal inhibition of 61% was observed. The D5 agonist SKF R-38393 (10 microM)
      mimicked this effect (28% inhibition). SCH 23390, a D5 antagonist, blocked the
      inhibition caused by both DA and SKF R-38393. Spiperone, a D2 receptor
      antagonist, did not block the inhibition. The D2 agonist (+/-)-2-(N-phenylethyl-N
      propyl)amino-5-hydroxytetralin (PPHT) did not inhibit TRH-stimulated IP
      production, nor did it augment the effect of D5 agonists. The DA-mediated
      suppression of IP levels was not sensitive to pertussis toxin; cholera toxin
      blocked both TRH stimulation and DA suppression of IP accumulation in response to
      100 nM TRH. Neither dibutyryl cAMP nor forskolin lowered IP formation in response
      to TRH. Phorbol ester decreased TRH-stimulated IP accumulation in D5GH4C1 cells;
      however, an inhibitor of protein kinase C (PKC) did not block the effect of DA.

PMID- 10087454
TI  - Prohormone convertases 1 and 2 process ProPACAP and generate matured, bioactive
      PACAP38 and PACAP27 in transfected rat pituitary GH4C1 cells.
AB  - Pituitary adenylate cyclase-activating polypetide (PACAP) exists in two amidated
      forms, PACAP38 and PACAP27, which are expressed in the magnocellular and
      parvocellular neurons of the paraventricular nucleus (PVN) and the magnocellular
      neurons of the supraoptic nucleus (SON) of the hypothalamus. The prohormone
      convertases PC1 and PC2, subtilisin-like PCs of the Kex2 family, are expressed in
      neuroendocrine cells. Immunocytochemistry and in situ hybridization of PC1 and
      PC2 in the hypothalamus have shown that PC1 and PC2 are also present in the PVN
      and SON. Therefore, it is possible that the precursor of PACAP is processed by
      PC1 and/or PC2 in the hypothalamic nuclei and then converted to its mature forms.
      To test this hypothesis, rat pituitary GH4C1 cells were supertransfected with
      human PACAP cDNA and either rat PC1 or PC2 cDNA. The acid extracts of these cells
      were analyzed by reversed-phase HPLC for proPACAP, PACAP38 and/or PACAP27
      radioimmunoassays using three antibodies with different recognition sites, and
      then bioassayed for the ability to stimulate adenylate cyclase. The cells
      transfected with PACAP cDNA alone yielded PACAP-like immunoreactivity (PACAP-li)
      corresponding to molecular weights between 15 and 20 kDa without PACAP
      bioactivity. Cotransfection of these cells with PC1 or PC2 generated PACAP-li,
      which coeluted with synthetic PACAP38 and PACAP27, respectively. Western blot
      also revealed 4.5- and 3.0-kDa PACAP-li bands, which correspond to the molecular
      weights of PACAP38 and PACAP27, respectively. The HPLC fractions containing PACAP
      li, which were coeluted with synthetic PACAP38 and PACAP27, showed marked
      bioactivities. These findings suggest that the precursor of PACAP expressed in
      the PVN and SON of the hypothalamus could be efficiently processed by PC1 and
      PC2, and then converted to mature, bioactive PACAP38 and PACAP27.

PMID- 10087455
TI  - Regional cerebral blood flow in schizophrenia using stable xenon-enhanced
      computed tomography.
AB  - To investigate the regional cerebral blood flow (rCBF) and the factors affecting
      the rCBF in schizophrenia, we measured the rCBF using stable xenon-enhanced
      computed tomography in 118 schizophrenic patients and 21 healthy subjects. A
      multiple regression analysis was applied to assess the potential affecting
      factors, i.e. age, gender, duration of illness, dose of antipsychotics and usage
      of antiparkinsonism and antianxiety drugs. The rCBF of the schizophrenic patients
      was significantly lower than that of the healthy subjects in all regions except
      for the occipital region. The rCBF was decreased with increasing age in both
      groups to the same extent. The dosage of antipsychotic drugs taken had a
      significant regression relationship with the rCBF in the bilateral thalamus.

PMID- 10087456
TI  - Pituitary-adrenal and parasympathetic function in chronic schizophrenic patients
      with postoperative ileus or hypotension.
AB  - We studied the relationship between parasympathetic, sympathetic and pituitary
      adrenal functions in chronic schizophrenic patients with complications such as
      postoperative paralytic ileus and hypotension during anaesthesia. Plasma
      epinephrine, norepinephrine (NE), adrenocorticotropin (ACTH), cortisol and the
      coefficient of variation (CV) of the R-R intervals on the electrocardiogram (ECG)
      as parasympathetic parameter were measured in schizophrenic and control patients.
      The CV value of the R-R interval on the ECG before the start of anaesthesia was
      significantly decreased to 2.3 +/- 0.2 in the schizophrenic patients as compared
      with 3.5 +/- 0.3 of the control patients. The CV value of the R-R interval on the
      ECG in schizophrenic patients with postoperative paralytic ileus was more
      diminished to 1.6 +/- 0.2. The CV values in schizophrenic patients with and
      without hypotension during anaesthesia were similar and we could not find any
      significant difference. Chronic schizophrenic patients developed a decrease in
      NE, ACTH and cortisol responses to surgical stress, while there were no
      significant differences in these hormonal changes between those patients with and
      without paralytic ileus and hypotension during anaesthesia. In conclusion, the CV
      value of the ECG R-R interval may be correlated inversely with the expectancy of
      postoperative ileus in chronic schizophrenic patients. Their suppressed pituitary
      adrenal function and sympathetic system may be indirectly associated with the
      paralytic ileus and hypotension.

PMID- 10087457
TI  - Contingent negative variation and attention in schizophrenic and depressed
      patients.
AB  - Contingent negative variation (CNV) is supposed to be a psychophysiological
      indicator of attention and arousal. Both have been reported to be deteriorated in
      schizophrenic and depressed patients. Thirty-four patients with major depression,
      43 patients with schizophrenia and 49 healthy subjects were investigated during
      acute illness with a complex three-stimulus go/no-go task which requires
      different states of attention: trials consisted of three complex figures that
      were tachistoscopically presented. Three identical figures had to be confirmed by
      pressing a button (target condition). CNV was measured: (1) after the first
      figure waiting for the second (baseline condition), (2) after two identical
      figures waiting for the third (response-relevant condition), (3) after two
      different figures waiting for the third (response-irrelevant condition). The
      response-relevant condition compared to baseline significantly intensified CNV in
      healthy controls and to a minor extent in depressed patients but not in
      schizophrenics. In the response-relevant conditions in healthy controls, CNV was
      significantly reduced compared to the response-relevant condition. This clear
      discrimination between response-relevant and response-irrelevant conditions was
      not observed in either group of patients. Thus, the applied CNV paradigm was able
      to discriminate schizophrenic and depressed patients from healthy controls.
      Furthermore, subtle differences between schizophrenic and depressed patients were
      detected, reflected by the different CNV development across experimental
      conditions.

PMID- 10087458
TI  - Apolipoprotein E genotype and schizophrenia.
AB  - Schizophrenic disorders are complex genetic disorders and may involve multiple
      genes of small effect. The presence of apolipoprotein E (apoE) is associated with
      several neuropsychiatric disorders. Previous studies on apoE genotype
      distribution in schizophrenia have reported conflicting findings. We studied the
      genotype frequencies in a large group of schizophrenic patients. The genotype
      distribution was significantly different between the schizophrenic patients and
      the control subjects. Persons who were sigma3 carriers have an increased risk of
      schizophrenia. This result suggests that apoE isoforms may play a functional role
      in the pathogenesis of schizophrenic disorders. Some possible mechanisms
      regarding the effect of apoE on the development of schizophrenia are discussed.

PMID- 10087459
TI  - Lower serum zinc in relation to serum albumin and proinflammatory cytokines in
      detoxified alcohol-dependent patients without apparent liver disease.
AB  - Recently, it was reported that there may be an activation of the inflammatory
      response system in detoxified alcohol-dependent patients without apparent liver
      disease (AWLD). The aims of the present study were to examine serum zinc (Zn)
      concentrations, total serum protein (TSP) and patterns obtained in the
      electrophoretically separated protein fractions in relation to serum interleukin
      6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP
      electrophoresis, and serum IL-6 and IL-8 concentrations were determined in
      detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and
      the serum concentrations of albumin (Alb) and the beta fraction were
      significantly lower in detoxified AWLD patients than in healthy volunteers. The
      percentage of the alpha2 fraction was significantly higher in detoxified AWLD
      patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered
      serum Alb. Lower serum Alb was significantly and negatively correlated to
      increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were
      significantly and positively related to serum IL-6 and IL-8. The results show
      that there is an in vivo activation of the inflammatory response system in
      detoxified AWLD patients and that lower serum Zn may be causally related to lower
      serum Alb.

PMID- 10087460
TI  - Efficiency of continuous positive airway pressure versus theophylline therapy in
      sleep apnea: comparative sleep laboratory studies on objective and subjective
      sleep and awakening quality.
AB  - Sleep apnea is the most common sleep-related breathing disorder characterized by
      repetitive episodes of hypoxemia. Therapies include behavioral, surgical,
      orthodontic, pneumological, and pharmacological interventions. The aim of the
      present study was to compare the efficiency of pneumological therapy by nasal
      continuous positive airway pressure (CPAP) versus a pharmacological approach with
      theophylline (Respicur retard(R) 400 mg) on respiratory variables as well as
      objective and subjective sleep and awakening quality in patients with moderate
      sleep apnea measured by polysomnography and psychometry. Under CPAP therapy all
      respiratory variables improved and normalized, while under theophylline only the
      apnea-hypopnea index and the desaturation index improved but still did not return
      to normal values. Regarding sleep initiation and maintenance, CPAP therapy
      prolonged sleep latency and reduced movement time, while patients treated with
      theophylline showed reduced total sleep period, total sleep time and sleep
      efficiency. Sleep architecture demonstrated an increase in deep sleep and REM
      stages under CPAP therapy, and remained unchanged under theophylline. Concerning
      subjective sleep and awakening quality, both treatments improved well-being in
      the morning. Regarding objective awakening quality, reaction time performance was
      improved in both groups. In conclusion, CPAP treatment is more effective than
      theophylline regarding respiratory variables as well as the normalization of
      sleep maintenance and sleep architecture in sleep apnea patients.

PMID- 10087461
TI  - Olfaction and hemispheric asymmetry: unilateral stimulation and bilateral
      electrodermal recordings.
AB  - The study of hemispheric asymmetry in olfaction in human subjects has given rise
      to many publications, but the findings have often been contradictory. This study
      used bilateral electrodermal activity recordings with unilateral stimulation as a
      measure of functional hemispheric asymmetry. A specific odorant (lavender) was
      used by monorhinic (single nostril) stimulation on 30 dextral subjects (20
      females and 10 males). Intraindividually, the results showed no difference
      between the two nostrils, but all subjects exhibited a constant direction of
      electrodermal asymmetry: 20 subjects systematically showed a greater response
      amplitude for the right hand and 10 subjects systematically showed a greater
      response amplitude for the left hand, whatever hemisphere stimulated.

PMID- 10087462
TI  - Association between delta waves during sleep and negative symptoms in
      schizophrenia. Pharmaco-eeg studies by using structurally different hypnotics.
AB  - We examined the effects of benzodiazepine (BZD) hypnotics and zopiclone (ZPC), a
      nonbenzodiazepine hypnotic, on sleep and psychiatric symptoms in schizophrenia,
      as well as the clinical correlates of these variables. Seven male schizophrenic
      patients chronically taking neuroleptics together with BZD were studied. We
      replaced BZD with ZPC and performed polysomnography (PSG) and Brief Psychiatric
      Rating Scale (BRPS) scoring before and after an 8-week ZPC treatment. The
      replacement of BZD with ZPC increased the mean amplitude of high-amplitude low
      frequency delta waves on the frontal derivation recognized by period-amplitude
      analysis, and it decreased the BPRS negative-symptom score. Under the BZD
      treatment, the negative-symptom score correlated inversely with the mean
      amplitude of high-amplitude low-frequency delta waves. This correlation was weak
      and not significant under the ZPC treatment. Therefore, delta waves during sleep
      have a close correlation to negative symptoms in schizophrenia, and such a
      correlation could be influenced by hypnotics. Although these are preliminary
      findings, it was suggested that, compared with BZD, ZPC might be a beneficial
      hypnotic in regard to both sleep and negative symptoms of chronic schizophrenic
      patients.

PMID- 10087463
TI  - Binding and functional potency of neurokinin A analogues in the rat fundus: A
      structure-activity study.
AB  - Structure-activity relationships of neurokinin A (NKA) and the two analogues
      NKA(4-10) and [Nle10]NKA(4-10) were investigated at the rat fundus NK-2 receptor,
      using selected amino acid substitutions. Both radioligand binding with
      [125I][Lys5,Tyr(I2)7,MeLeu9, Nle10] NKA(4-10) and functional studies were
      performed and correlated. In membrane binding experiments loss of His1 and Lys2,
      or replacement of Lys2 with Ala did not substantially alter binding affinity of
      NKA. NKA(4-10) free acid was unable to compete with the radioligand. [Nle10]NKA(4
      10) binding affinity to rat fundus membrane preparations was decreased when
      substituting Asp4 with Gln or Asn, or Val7 with either Tyr or Ile. Replacement of
      Ser5 with the negatively charged Glu also decreased the binding affinity, but
      substitution with the positively charged Lys substantially increased the affinity
      of [Nle10] NKA(4-10) for the NK-2 receptor. Lengthening NKA(4-10) or [Nle10]NKA(4
      10) with Ala11 or Nle11, respectively, decreased the binding affinity of the
      peptide. In both binding and functional studies, replacement of any of the
      residues of NKA(4-10), except for Ser5, with alanine decreased the affinity of
      the peptide for the NK-2 receptor. Ala substitutions at positions 4, 6, and very
      obviously at 8, 9 and 10 of NKA(4-10) yielded peptides unable to achieve a
      maximum contractile response, although they did not demonstrate antagonist
      activity. These data confirm the importance of the NKA carboxyl terminus, and the
      requirement for Phe6, Val7, Gly8, Leu9 and Met10 integrity for interaction with
      the NK-2 receptor. They also suggest that Ser5 is a good site to target
      modifications leading to the design of new potential drugs.

PMID- 10087464
TI  - Junctional transmissions in smooth muscle of the guinea pig duodenum and their
      modulation by the prokinetic agent DQ-2511.
AB  - Junctional transmissions and their modulation by DQ-2511, a novel prokinetic
      agent, were investigated in smooth muscle of the guinea pig duodenum. Transmural
      nerve stimulation evoked a cholinergic excitatory junction potential, a
      nonadrenergic, noncholinergic inhibitory junction potential, and a substance P
      mediated slow depolarization. DQ-2511 showed dual effects on the slow
      depolarization: a low concentration (10(-9) mol/l) enhanced and high
      concentrations (>10(-6) mol/l) tended to inhibit. The depolarization produced by
      exogenously applied substance P was enhanced by low concentrations of DQ-2511.
      The results suggest that the prokinetic actions of DQ-2511 involve an enhancement
      of transmission from substance P neurons due to an increase in sensitivity of
      postjunctional receptors to substance P.

PMID- 10087465
TI  - Inhaled nitric oxide potentiates actions of adenosine but not of sodium
      nitroprusside in experimental pulmonary hypertension.
AB  - Inhaled nitric oxide (NO), a selective pulmonary vasodilator, increases
      intracellular cyclic guanosine monophosphate. In contrast, adenosine, another
      selective pulmonary vasodilator, increases intracellular cyclic adenosine
      monophosphate. There has been only limited study on effects of inhaled NO
      combined with other pulmonary vasodilators. The current study examined the
      hypothesis that inhaled NO would potentiate in vivo pulmonary vasodilator effects
      of adenosine, but not those of sodium nitroprusside (SNP). Like inhaled NO, SNP
      acts via cyclic guanosine monophosphate. Rabbits were anesthetized and
      mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl
      ester was administered. U46619, a thromboxane A2 mimetic, was infused to produce
      pulmonary hypertension. Rabbits then received either SNP at doses of 0.5, 1, 2,
      4, 8, 16, and 32 microg/kg/min or adenosine at doses of 12.5, 25, 50, 100, 150,
      and 300 microg/kg/min. Hemodynamic measurements were obtained with or without
      inhaled NO (40 ppm) at each dose of SNP or adenosine. During U46619-induced
      pulmonary hypertension, inhaled NO decreased pulmonary artery pressure and
      pulmonary vascular resistance. Adenosine and SNP produced dose-related decreases
      in pulmonary artery pressure and pulmonary vascular resistance and increases in
      cardiac output. Inhaled NO decreased pulmonary artery pressure and pulmonary
      vascular resistance at all doses of adenosine, but had no significant pulmonary
      vasodilator effects at doses of SNP >0.5 microg/kg/min. We conclude that inhaled
      NO does not produce additional pulmonary vasodilation over that achieved at
      higher doses of SNP, but does produce additional vasodilation when combined with
      a vasodilator having different mechanisms of action. Since both inhaled NO and
      adenosine produce selective pulmonary vasodilation, such combination therapy may
      be effective in patients with pulmonary hypertension.

PMID- 10087466
TI  - Correlation between the in vivo efficacy of GPIIb/IIIa receptor antagonists
      (m7E3, MK-383 and DMP-728) and ex vivo platelet inhibition.
AB  - In vivo antithrombotic efficacy of GPIIb/IIIa receptor antagonists (m7E3, MK-383
      and DMP-728) was studied with respect to their ex vivo platelet inhibition in
      heparinized platelet-rich plasma (hPRP) and citrated platelet-rich plasma (cPRP)
      using a canine model of carotid artery thrombosis. For each drug group (n = 6),
      the right carotid artery was used as control vessel and resulting occlusive
      thrombus was kept in situ to examine the direct thrombolytic efficacy of the
      antagonists. Thirty minutes after occlusion of control vessel, a low or high dose
      of each antagonist was administered and the left carotid artery was used as test
      vessel. All control vessels occluded within 86-96 min in response to electrolytic
      injury. The incidence of occlusion with lower doses of m7E3, DMP-728, and MK-383
      was 100, 33 and 100%, respectively; corresponding times to occlusion were 174,
      220 and 118 min. Lower doses inhibited ADP- or AA-induced platelet aggregation in
      cPRP (>80%). Incidence of occlusion with high doses of m7E3, DMP-728 and MK-383
      was 33, 0 and 0%, respectively; corresponding times to occlusion were 209, >240
      and >240 min. Higher doses inhibited aggregation in cPRP (>80%), but only
      partially in hPRP (45-66%). Dose-dependent prolongation of bleeding time occurred
      with all antagonists. None of the antagonists lyzed preformed thrombi in control
      vessels. The results indicate that ex vivo platelet aggregation conducted in
      hPRP, as opposed to conventional cPRP, provides a better assessment of the in
      vivo efficacy of GPIIb/IIIa receptor antagonists.

PMID- 10087467
TI  - Misoprostol-inhibited rat gastric emptying is independent of gastric inhibitory
      polypeptide release.
AB  - We studied the effects of orally or intraperitoneally administrated misoprostol
      on rat gastric emptying and looked what was the role of gastric inhibitory
      polypeptide (GIP) in this emptying. The rats initially received oral misoprostol
      at doses of 1, 10, 50, and 100 microg/kg. Another group of rats received
      misoprostol intraperitonally at doses of 10, 50, 250, and 500 microg/kg. Using an
      oral radiochromium motility marker, the liquid gastric emptying was measurement
      30 min after misoprostol treatment. The plasma GIP levels were measured by a home
      made radioimmunoassay kit. Oral treatments at the doses of 1 and 10 microg/kg did
      not influence emptying, whereas other doses delayed emptying (p < 0.01). Except
      the 10- microg/kg injection, other doses exhibited a dose-dependent inhibition in
      emptying (p < 0.01). Neither oral feeding nor intraperitoneal injection changed
      plasma GIP levels. We conclude that liquid gastric emptying is disturbed after
      various routes of misoprostol treatment; GIP appears less important in the
      misoprostol-mediated gastric emptying.

PMID- 10087468
TI  - Captopril inhibits peptidylglycine- alpha-hydroxylating monooxygenase:
      implications for therapeutic effects.
AB  - The therapeutic actions of captopril are facilitated by its sulfhydryl moiety
      which interacts with the metal (Zn2+) prosthetic groups of angiotensin-converting
      enzyme (ACE; EC 3.4.15.1). This study focused on captopril as an inhibitor of
      another metal-dependent (Cu2+) enzyme, peptidylglycine-alpha-hydroxylating
      monooxygenase (PHM; EC 1.14.17.3). PHM is rate limiting in alpha-amidation, a
      COOH-terminal modification that bioactivates several pressor peptides. Captopril
      inhibited PHM in vitro in a dose-dependent manner with an IC50 of approximately
      100 micromol/l. This inhibition was partially reversed by increased
      concentrations of Cu2+. Structurally similar nonsulfhydryl ACE inhibitors did not
      affect the activity of PHM. The present findings indicate that the therapeutic
      effectiveness of captopril may result from actions on a range of metalloenzymes
      including ACE and PHM.

PMID- 10087469
TI  - The effect of LINAC stereotactic radiosurgery on epilepsy associated with
      arteriovenous malformations.
AB  - Reduction of seizures associated with arteriovenous malformations (AVMs)
      following radiosurgery has been reported. This investigation assessed the effect
      of LINAC radiosurgical treatment of AVMs on the associated epilepsies correlated
      to AVM location, size, seizure type, and postradiosurgical thrombosis. Of 100
      patients with AVMs, 33 presented with seizures (11 generalized tonic-clonic
      seizures, 8 simple partial seizures, and 14 complex partial seizures with or
      without secondary generalization). Patients with AVMs >/=25.0 mm were more likely
      to have seizures. Patients with frontal lobe AVMs were the most likely to have
      associated epilepsy (72.7%). Following radiosurgery, 59% were seizure-free and
      19% had marked reduction of seizure frequency. Seizure remission was most
      frequent for AVMs of the centrum (83.3%). Of 14 patients with 2-year follow-up
      angiography, 9 had complete thrombosis and 6 became seizure-free. Four of 5
      patients without thrombosis also became seizure-free. We conclude that LINAC
      radiosurgery is effective for epilepsies associated with AVMs. Radiosurgery was
      most effective for generalized tonic-clonic and complex partial seizures. There
      was no statistically significant correlation between reduction in epilepsy and
      original AVM size. Four of 5 patients without thrombosis became seizure-free,
      suggesting that structural or biochemical alterations of epileptogenic neurons
      following radiosurgery may reduce epileptogenicity.

PMID- 10087470
TI  - Frameless laser-guided stereotaxis: A system for CT-monitored neurosurgical
      interventions.
AB  - OBJECTIVE: Since a simple, rapid and accurate stereotactic system allowing CT
      monitoring would offer the neurosurgeon several advantages, the feasibility and
      application accuracy of frameless laser-guided freehand point stereotaxis for
      neurosurgical interventions was studied. METHODS: A Cartesian coordinate grid
      mounted upon the far wall of a CT scan room defined a plane. The scanner
      isocenter defined the origin of a three-dimensional coordinate system. Phantom
      entry point and target point coordinates were determined by the positional CT
      cursor. These coordinates were entered into a computer which determined the
      coordinates of the grid intersection point with a line passing through the entry
      and target points. A tripod-mounted laser assembly comprising two encased lasers
      oriented retrograde and antegrade along opposite vectors, was positioned near the
      grid. The retrograde laser was positioned to illuminate the marked grid
      intersection point while the antegrade laser simultaneously illuminated the entry
      point; the beams were thereby aligned along the line of trajectory. The tip of a
      probe was placed on the entry point; the hub was then moved into the path of the
      antegrade laser, thereby aligning the probe with the line of trajectory. The
      probe was then inserted to the target at a trigonometrically calculated distance.
      RESULTS: Ten consecutive phantom tests averaged 17.5 min. Phantom test
      application accuracy averaged +/-2 mm at an average insertion distance of 7.1 cm.
      CONCLUSION: Phantom tests indicate that simple, rapid and accurate CT-monitored
      frameless laser-guided freehand point stereotaxis is feasible. Clinical
      investigation is warranted.

PMID- 10087471
TI  - Results and complications from the use of a frameless stereotactic microscopic
      navigator system.
AB  - We present a series of 21 patients, 12 males and 9 females, aged 41-76 years,
      with the preoperative diagnosis of a brain tumor. Both preoperatively and
      postoperatively, all of our patients underwent either a brain computed tomography
      (CT) or magnetic resonance imaging (MRI). All the radiographic studies were taped
      and loaded preoperatively in the Stereotactic Microscopic Navigator (SMN)
      workstation (Zeiss, Germany). The mean duration of this procedure was 25 +/- 6
      min. All our patients were operated on in our institute with the use of the SMN
      system. The specificity of tumor localization using CT scan was 2.20 +/- 0.25 mm
      and for the MRI scan 2.6 +/- 0.25 mm. As assessed by postoperative radiographic
      studies, total gross tumor resection was possible in 20 patients (95.23%). No
      major intraoperative or early postoperative complications were noted in our
      series. We believe that the SMN system is a safe, well-tolerated by the patients
      and simple method with extremely high accuracy and specificity.

PMID- 10087472
TI  - Balloon compression of the Gasserian ganglion for the treatment of trigeminal
      neuralgia.
AB  - The authors describe the results of the treatment of trigeminal neuralgia by
      balloon microcompression of the Gasserian ganglion. One hundred and eighty-seven
      procedures were performed in 158 patients. There were no deaths or complications
      of clinical importance and pain was relieved in all patients. It was concluded
      that the treatment of trigeminal neuralgia by the microcompression method is
      safe, simple, cheap, and is especially recommended in cases of pain affecting the
      first division of the trigeminal nerve and in clinically ill or non-cooperative
      patients.

PMID- 10087473
TI  - Effect of fentanyl and naloxone on a thalamic induced painful response in
      intractable epileptic patients.
AB  - Acute high-frequency (60/s) high-intensity (2,100-2,300 microA) stimulation of
      the mesial, caudal and inferior portion of the centromedian thalamic region
      within or close to the parafascicular nucleus produced a sharp, intense, cramp
      like painful response localized to the face and shoulder (medial stimulation) or
      arm and hand (lateral stimulation) contralateral to the stimulation site in 4
      intractable epileptic patients in whom depth electrodes had been implanted as a
      part of a neuroaugmentive procedure for seizure control. This thalamic induced
      painful response was always accompanied by objective clinical signs (facial
      gesticulation and contraction of the corresponding muscles) during thalamic
      stimulation and significant increments in EEG, EKG and respiratory frequencies
      and EMG muscular tonus from 10 s before to 10 s after thalamic stimulation.
      Opioid agonists (fentanyl 5.0 microg/kg) and antagonists (naloxone 3.5 microg/kg)
      were administered to induce and regulate a state of neuroleptanalgesia used for
      the subcutaneous internalization of the chronic stimulation systems. Under these
      conditions, we observed that fentanyl greatly attenuated and naloxone increased
      the intensity of the painful response, as well as the EEG, somatic and vegetative
      parameters evaluating such a painful response. Differences were significant when
      one compares the changes in response to electrical stimulation in EEG, EKG,
      respiration and EMG after the administration of fentanyl (decrease p = 0.001) and
      naloxone (increase p = 0.01) compared to those obtained after the administration
      of saline or no drugs during baseline recordings. These data suggest that this
      thalamic induced painful response is mediated by inhibition or activation of the
      morphine receptors of the thalamic cells primarily related to the pain process.

PMID- 10087474
TI  - [Clinical significance of improved persistent defect by thallium-201 reinjection
      imaging in the subacute phase of myocardial infarction].
AB  - The clinical significance of new fill-in observed by thallium-201 (201Tl)
      reinjection in myocardial segments with persistent defect in the subacute phase
      of myocardial infarction was investigated. Seventy-five patients with subacute
      phase (mean 20th day) of first myocardial infarction underwent stress
      redistribution-reinjection 201Tl single photon emission computed tomography
      (SPECT) imaging. Percentage 201Tl uptake was calculated and classified as
      persistent defect without fill-in even after reinjection (PD group, n = 26, 35%),
      persistent defect with new fill-in after reinjection [REINJ (+) group, n = 19,
      25%] and reversible defect [RD (+) group, n = 24, 32%]. The clinical features and
      angiographic findings were assessed in the same phase in each group. Diameter
      stenosis of the infarction-related arteries by coronary angiography was 68 +/-
      34% in the PD group, 31 +/- 23% in the REINJ (+) group and 83 +/- 27% in the RD
      (+) group [p < 0.01, REINJ (+) group vs PD group and RD (+) group]. Wall motion
      of the infarcted myocardial segments significantly improved and the mean left
      ventricular ejection fraction (EF) was higher in the REINJ (+) group than in the
      PD group (mean EF 51% vs 43%, p < 0.01). Post infarction angina was more frequent
      in the RD (+) group than in the REINJ (+) group (38% vs 5%, p < 0.05). Although
      new fill-in-after 201Tl reinjection has been considered to indicate severe
      myocardial ischemia in chronic coronary disease, these results indicate that this
      phenomenon in viable myocardium in patients with subacute phase of myocardial
      infarction is not always related to residual ischemia in the infarcted myocardial
      area.

PMID- 10087475
TI  - [Usefulness of exercise echocardiography in ischemic heart disease: comparison
      with exercise cardiac scintigraphy].
AB  - Exercise echocardiography and exercise thallium-201 (201Tl) single photon
      emission computed tomography (SPECT) were performed in 152 patients with
      suspected coronary artery disease, including 61 patients with old myocardial
      infarction. All patients underwent coronary arteriography, and coronary artery
      disease was defined as > or = 75% diameter stenosis. Digital two-dimensional
      echocardiography was performed before and after the treadmill exercise test, and
      wall motion abnormality was evaluated using quad-screen. Sensitivity and
      specificity for the diagnosis of coronary artery disease were similar for the 2
      exercise tests (77% and 80% for echocardiography and 75%, and 83% for SPECT,
      respectively). Diagnoses for one-vessel disease, 2-vessel disease and 3-vessel
      disease were similar for echocardiography (79%, 72% and 77%, respectively) and
      SPECT (74%, 75% and 77%, respectively). Sensitivity for the diagnosis of ischemia
      at the area remote from infarct area was low for both exercise echocardiography
      and exercise SPECT (45% and 48%, respectively). Exercise echocardiography has
      comparable diagnostic value to SPECT for the detection of coronary artery
      disease. However, both exercise tests have limitations for the diagnosis of
      ischemia at the area remote from infarct area.

PMID- 10087476
TI  - [Preventive mechanisms and effects of pemirolast potassium on restenosis after
      percutaneous transluminal coronary angioplasty: serial coronary angiography and
      intravascular ultrasound studies].
AB  - Pemirolast potassium, an antiallergic agent, has preventive effects against
      restenosis after percutaneous transluminal coronary angioplasty (PTCA). This
      study investigated the mechanism of the preventive effects of pemirolast on
      restenosis using serial intravascular ultrasound (IVUS). Initial elective PTCA
      was performed in consecutive 106 patients from March 1996 through August 1997.
      Patients with type C lesions or graft stenosis were excluded from the study. A
      total of 97 patients with 110 lesions, 48 patients (56 lesions) in the pemirolast
      treated group and 49 patients (54 lesions) in the control group were analyzed.
      Restenosis was defined as a diameter stenosis of > or = 50% at follow-up study.
      Patients in the pemirolast group received 20 mg/day from the morning after
      angioplasty until the time of follow-up (mean 6 months). The lumen cross
      sectional area, vessel area, plaque area, and % plaque area were measured by
      quantitative coronary ultrasound and compared after PTCA and at follow-up between
      the patients without restenosis in the pemirolast (28 lesions) and control (27
      lesions) groups. There was no significant change in baseline characteristics
      between the 2 groups. Restenosis rate per lesion was significantly lower in the
      pemirolast group than in the control group (23.2% vs 44.4%, p < 0.05,
      respectively). After angioplasty and at follow-up study, there was no difference
      in lumen and vessel cross-sectional areas between the 2 groups. However, plaque
      and % plaque area in the pemirolast group were smaller than in the control group
      at follow-up study (8.9 +/- 2.3 vs 11.8 +/- 3.5 mm2, p < 0.005, 56.0 +/- 9.0% vs
      64.0 +/- 10.4%, p < 0.005, respectively). These results suggest that suppression
      of neointimal hyperplasia is the preventive mechanism of pemirolast against
      restenosis after angioplasty. Pemirolast may be more effective against restenosis
      after coronary stenting.

PMID- 10087477
TI  - [Unruptured aneurysm of the right sinus of Valsalva: a case report].
AB  - A previously healthy and asymptomatic 45-year-old woman was referred for
      evaluation of a heart murmur and an unusual dilatation in the aortic root.
      Transthoracic and transesophageal echocardiography, computed tomography, magnetic
      resonance imaging, and cardiac catheterization revealed an aneurysm with a
      maximum diameter of 6.0 cm in the right sinus of Valsalva. Aortic regurgitation
      and stenosis at the right ventricle outflow tract were associated with the
      aneurysm. Surgery and histological study demonstrated that the sinus of Valsalva
      aneurysm was enormously dilated with idiopathic degenerative change in the aortic
      media. The aneurysm was tremendously large compared to any previously reported.
      Decrease in pressure load during diastole caused by aortic regurgitation probably
      resulted in the growth of this huge aneurysm without rupture.

PMID- 10087478
TI  - [Usefulness of tissue harmonic imaging for the detection of left ventricular
      endocardial border].
AB  - Assessment of segmental wall motion is one of the most challenging tasks in
      echocardiography. One major limitation is impairment of echocardiographic
      regional wall motion by incomplete endocardial definition. The newly developed
      tissue harmonic imaging method may improve the detection of left ventricular
      endocardial border. This study examined the impact of native tissue harmonic
      imaging on endocardial border definition. Fundamental and harmonic imaging were
      compared for detecting the endocardial border in 96 segments of 16 patients (age
      54 +/- 8 years). Visualization of endocardial border was better with harmonic
      imaging than with fundamental mode in 49% (47 of 96 segments). Thus, tissue
      harmonic imaging has a significant impact on endocardial border definition.

PMID- 10087479
TI  - [Endothelium-dependent relaxation of collateral microvessels following
      intramuscular gene transfer of vascular endothelial growth factor in a rat model
      of hindlimb ischemia].

PMID- 10087480
TI  - [Enhanced shear-induced platelet aggregation in acute myocardial infarction].

PMID- 10087481
TI  - [Increased expression of P-selectin on platelets is a risk factor for silent
      cerebral infarction in patients with atrial fibrillation: role of nitric oxide].

PMID- 10087482
TI  - [Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis].

PMID- 10087483
TI  - [Genetic polymorphisms of methylenetetrahydrofolate reductase and methionine
      synthase: association with homocysteine metabolism and late-onset vascular
      diseases in the Japanese population].

PMID- 10087484
TI  - [A 56-year-old woman complaining of faintness].

PMID- 10087485
TI  - A 68-year-old man with complete atrioventricular block and congestive heart
      failure.

PMID- 10087486
TI  - Distribution of T-lymphocyte subpopulation in blood and spleen of normal cattle
      and cattle with enzootic bovine leukosis.
AB  - Immunocytochemical and flow cytometry techniques were used to examine T
      lymphocyte subpopulations in peripheral blood lymphocytes (PBLs) and spleen from
      cases of enzootic bovine leukosis (EBL) in adult cattle, and from normal cattle
      (adult and young), with a panel of monoclonal antibodies against bovine leucocyte
      differentiation molecules. Both in PBLs and spleen, the percentages of T
      lymphocyte subpopulations (CD3+, CD4+, CD8+, and WC1 + gamma delta T lymphocytes)
      of EBL-affected and normal adult cattle were significantly lower than those of
      normal young cattle. The percentages of these T-lymphocyte subpopulations in the
      PBLs of adult cattle with EBL were lower than those of normal adult cattle, but
      the converse was true in the spleen. It is suggested that tumour immunity
      occurred in the spleen. Histological examination revealed no follicular
      hyperplasia in the spleen, and the proliferation of neoplastic cells began in the
      red pulp. It is concluded that the spleen is not the organ initially responsible
      for the transformation of EBL lymphoma and that neoplastic cells migrating from
      peripheral blood are metastatic.

PMID- 10087487
TI  - Analysis of leucocyte subsets in the canine intestine.
AB  - Immunohistochemistry and computer-aided morphometric analysis were used to define
      populations of leucocyte subsets in the intestinal tract of an outbred population
      of dogs with no evidence of gastrointestinal disease. In the small intestinal
      lamina propria, B cells and plasma cells (IgA+, IgM+ and IgG+) were prominent in
      peri-crypt regions, with a significant trend for a reduction in the number of
      cells towards the villous tip (P < 0.0001). By contrast, lamina propria T cells
      (CD3+) and T-cell subsets (CD4+ and CD8+) were present in greatest numbers at the
      tip of the villus, with significantly decreasing numbers towards the crypt
      regions (P < 0.0001). In the lamina propria, CD4+ cells outnumbered CD8+ cells (P
      = 0.05), but the opposite was true of the epithelial compartment (P < 0.001). The
      distribution of CD5+ lymphocytes was similar to that of CD3+ cells, in both the
      lamina propria and epithelial compartments. The numbers and distribution of cells
      expressing MHC class II, L1 and CD45 were recorded. Numerous eosinophils were
      present in the lamina propria, and an intra-epithelial population was also noted,
      especially in the crypt epithelium. Mast cells, which were mainly found in the
      subepithelial lamina propria, were also present within muscle layers, and cells
      expressing IgE had a similar distribution. Similar populations of cells were
      recorded in the colonic lamina propria and epithelium. The quantitative and
      qualitative data from this study will enable comparisons to be made with dogs
      suffering from inflammatory bowel diseases.

PMID- 10087488
TI  - Experimental lead toxicosis of raccoons (Procyon lotor).
AB  - Four pairs of raccoons were treated orally with the following doses of lead
      acetate (mg/kg; 5 days/week, for 8 weeks): 0 (control), 1, 2 and 4. In the six
      experimental animals, this treatment produced dose-dependent increases in blood
      lead, without clinical signs or changes in haematological parameters. After 8
      weeks, the liver and kidney of all lead-treated animals and the calvarium and
      radius of those receiving doses of 2 and 4 mg/kg contained elevated
      concentrations of lead. Acid-fast inclusions were observed by light and electron
      microscopy in the kidneys of all raccoons receiving the two highest doses and in
      one animal receiving the lowest dose. Hepatic acid-fast inclusions were seen in
      only one animal (dose 4 mg/kg). No inclusions were seen in osteoclasts of the
      radius. It is suggested that the findings, which support earlier observations
      that raccoons are fairly resistant to lead, may be of value in studying
      interactions between lead exposure and oral vaccination of wildlife against
      rabies.

PMID- 10087489
TI  - T-cell-rich B-cell lymphoma in the cat.
AB  - The clinical and pathological features of eight cases of feline T-cell-rich B
      cell lymphoma are described. The disease occurred in older cats (mean age 11.4 +/
      3.9 years), which on initial examination generally showed enlargement of a
      single submandibular or cervical lymph node. After excision, there was no
      recurrence of the lesions at 6 months in three cats. In one further case,
      however, the lesion had recurred 6 months later; it was again excised but
      recurred after an additional 6 months. Microscopically, there was effacement of
      normal lymph node architecture by a nodular (n = 4) or diffuse (n = 4)
      proliferation of small to blastic lymphocytes, accompanied by a characteristic
      population of bizarre giant, or multinucleate, cells. The mitotic rate was low
      and mitoses were restricted to the atypical population. Immunophenotyping
      revealed the smaller lymphocytes to be a mixture of CD3+ MHC Class II+ T
      lymphocytes and BLA36+CD79variable MHC Class IIvariable B lymphocytes. The
      atypical cells were of the B-cell lineage (BLA36+MHC Class IIvariable).
      Polymerase chain reaction analysis revealed no proviral DNA products of feline
      leukaemia virus or feline immunodeficiency virus in tissue from any tumour,
      confirming that these neoplasms were not associated with either virus. The
      clinical, histological and immunophenotypic findings in these cats were identical
      with those of "nodular lymphocyte predominance (lymphocytic and histiocytic/L&H)
      Hodgkin's disease" in man.

PMID- 10087490
TI  - Immunohistochemical detection of p53 and c-myc proteins in canine mammary
      tumours.
AB  - The objectives of this study were to detect by immunohistochemical means, nuclear
      accumulations of p53 and c-myc proteins in mammary tumours of dogs. Moderate or
      intense p53 protein nuclear labelling was shown by each of five osteosarcomas. In
      contrast, focal immunoreactivity was shown by three of five adenocarcinomas and
      two of three malignant myoepitheliomas. Six benign mixed tumours and three
      myoepitheliomas showed no detectable immunoreactivity. On the other hand, three
      patterns of c-myc protein nuclear reactivity were observed in these tumours.
      Osteosarcomas, adenocarcinomas, malignant myoepitheliomas and myoepitheliomas
      showed intense or moderate reactivity. In benign mixed tumours, the epithelial
      component showed moderate or intense reactivity, and the myoepithelial component
      showed focal or moderate reactivity. These results demonstrated that p53 protein
      was expressed only in the osteosarcomas, but that c-myc expression was detectable
      in both the epithelial and myoepithelial components.

PMID- 10087491
TI  - Phenotypic characterization of histiocytes infiltrating a leiomyofibrosarcoma.
AB  - We described previously a unique cutaneous tumour in a young pig, which was
      characterized by several criteria as a histiocytic leiomyofibrosarcoma. The lipid
      laden macrophages (histiocytes) which permeated the tumour were CD2+/CD18+/CD49d+
      but MAC387 (L1 antigen) and CD15 negative. The present study compared the
      phenotypes of histiocytes in tumour metastases in the liver with resident liver
      macrophages, revealing differential expression of certain macrophage activation
      markers. After repeated subcutaneous passage of the tumour in athymic (nu/nu)
      mice, flow cytometry demonstrated a rapid loss of porcine MHC Class II, but a
      more prolonged expression of porcine MHC Class I, consistent with our
      immunohistological observations. Mouse macrophages (CD2+/F4.80+) infiltrated the
      later-passage tumours, suggesting that the histiocytes were not of neoplastic
      origin.

PMID- 10087492
TI  - Mast cell density and subtypes in the skin of dogs with atopic dermatitis.
AB  - Skin biopsies from seven dogs with atopic dermatitis and 13 dogs with no clinical
      or histological evidence of skin diseases were examined. The study of the atopic
      dogs included 11 biopsy samples of nonlesional skin and 15 samples of lesional
      skin. One section of each tissue sample was stained with haematoxylin and eosin
      and another with toluidine blue to demonstrate the sulphated acid
      glycosaminoglycans in mast cell (MC) granules. To investigate MC subtypes, the MC
      specific proteases tryptase and chymase were examined by a double enzyme
      immunohistochemical staining technique. With the double labelling technique a
      significantly lower mast cell density was demonstrated in lesional (P = 0.0023)
      and nonlesional (P = 0.0004) skin samples of the atopic dogs than in the skin of
      control dogs. In the dermis of control dogs, a median mast cell density of 31.2
      MC/mm2 was detected with the toluidine blue staining method and of 27.5 MC/mm2
      with the double labelling technique. In lesional dermis of atopic dogs 29.8
      MC/mm2 were seen with toluidine blue while only 12.4 MC/mm2 were stained with the
      double labelling method (P = 0.0027). A similar difference was observed in
      nonlesional dermis samples, in which a mast cell density of 23.3 MC/mm2 was
      detected with toluidine blue but only 6.4 MC/mm2 with the double labelling method
      (P = 0.0127). The data provide evidence that mast cell granule heterogeneity
      exists in the dog and suggests that degranulation occurs selectively, depending
      on the pathological condition of the canine skin. Further investigations on the
      pathophysiological role of mast cell subtypes may help to elucidate the
      pathogenesis of atopic dermatitis.

PMID- 10087493
TI  - Pathological and immunohistochemical study of the liver and hepatic lymph nodes
      in goats infected with one or more doses of Fasciola hepatica.
AB  - Lesions produced by Fasciola hepatica in the liver, gall-bladder and hepatic
      lymph nodes (HLNs) of four groups of five goats are described; in addition, the
      distribution of CD3+ T lymphocytes and IgG-lambda light chain-bearing cells was
      analysed in the hepatic lesions and HLNs. One group of goats received a single
      oral dose of metacercariae, but the other four groups received four or five doses
      at different intervals over a period of 11 weeks. Animals that survived were
      killed 53-55 weeks after the first infective dose. Goats were more susceptible to
      multiple doses than to a single dose, even when the total number of metacercariae
      was the same. This greater susceptibility was manifested by the occurrence of
      deaths and the severity of hepatic lesions. CD3+ lymphocytes were sparse in the
      infiltrate surrounding the acute migratory tracts, suggesting inhibition of the
      local cell-mediated immune response. Goats with numerous hepatic calcareous
      granulomas showed the most severe hepatic damage, including marked cirrhosis,
      with a striking infiltrate of CD3+ T lymphocytes and lambda IgG- plasma cells,
      replacing extensive areas of hepatic parenchyma, in which hypertrophy of the
      smooth endoplasmic reticulum of hepatocytes was evident. These findings were
      observed mainly in the goats given more than one infective dose.

PMID- 10087494
TI  - Hypereosinophilic syndrome with Hodgkin's-like lymphoma in a ferret.
AB  - Hodgkin's-like lymphoma involving the lung, mediastinum, liver, kidneys and
      mesenteric lymph nodes was diagnosed in a ferret. The diagnosis was based on the
      presence of an admixture of CD3+ small lymphocytes with smaller numbers of
      macrophages, eosinophils, and large, pleomorphic, frequently multinucleated, Reed
      Sternberg-like cells which were immunoreactive to BLA.36 monoclonal antibody. In
      addition, the liver, pancreas, small intestine and lungs were infiltrated with
      moderate to large numbers of eosinophils, forming eosinophilic granulomas with
      occasional deposition of Splendore-Hoeppli material, supporting a diagnosis of
      hypereosinophilic syndrome. The concurrent diagnosis of hypereosinophilic
      syndrome and Hodgkin's-like lymphoma in this ferret provides further support to
      the concept that, in animals, multisystemic eosinophilic infiltrates may be
      caused by the abnormal proliferation of T lymphocytes, as has been demonstrated
      in man.

PMID- 10087495
TI  - Comparative molecular similarity index analysis (CoMSIA) to study hydrogen
      bonding properties and to score combinatorial libraries.
AB  - Comparative molecular field analysis has been applied to a data set of
      thermolysin inhibitors. Fields expressed in terms of molecular similarity indices
      (CoMSIA) have been used instead of the usually applied Lennard-Jones- and Coulomb
      type potentials (CoMFA). Five different properties, assumed to cover the major
      contributions responsible for ligand binding, have been considered: steric,
      electrostatic, hydrophobic, and hydrogen-bond donor or acceptor properties. The
      statistical evaluation of the field properties by PLS analysis reveals a similar
      predictive potential to CoMFA. However, significantly improved and easily
      interpretable contour maps are obtained. The features in these maps intuitively
      suggest where to modify a molecular structure in terms of physicochemical
      properties and functional groups in order to improve its binding affinity. They
      can also be interpreted with respect to the known structural protein environment
      of thermolysin. Most of the highlighted regions in the maps are mirrored by
      features in the surrounding environment required for binding. Using the derived
      correlation model, different members of a combinatorial library designed for
      thermolysin inhibition have been scored for affinity. The results obtained
      demonstrate the prediction power of the CoMSIA method.

PMID- 10087496
TI  - Functional concerted motions in the bovine serum retinol-binding protein.
AB  - The large concerted motions in the apo/holo bovine serum retinol-binding protein
      were studied using molecular dynamics simulation and 'essential dynamics'
      analysis. Initially, concerted motions were calculated from conformational
      differences between various crystal structures. The dynamic behaviour of the
      protein in the configurational space directions, described by these concerted
      motions, is analysed. This reveals that the large backbone dynamics of the
      protein is not influenced by the presence of retinol. Study of free retinol
      dynamics and retinol in the retinol binding site reveals that the protein binds
      retinol in a favourable conformation, as opposed to what has been previously
      described for the bovine cellular retinol-binding protein.

PMID- 10087497
TI  - Essential dynamics/factor analysis for the interpretation of molecular dynamics
      trajectories.
AB  - Subject of this work is the analysis of molecular dynamics (MD) trajectories of
      neurophysins I (NPI) and II (NPII) and their complexes with the neurophyseal
      nonapeptide hormones oxytocin (OT) and vasopresssin (VP), respectively, simulated
      in water. NPs serve in the neurosecretory granules as carrier proteins for the
      hormones before their release to the blood. The starting data consisted of two
      pairs of different trajectories for each of the (NPII/VP)2 and (NPI/OT)2
      heterotetramers and two more trajectories for the NPII2 and NPI2 homodimers (six
      trajectories in total). Using essential dynamics which, to our judgement, is
      equivalent to factor analysis, we found that only about 10 degrees of freedom per
      trajectory are necessary and sufficient to describe in full the motions relevant
      for the function of the protein. This is consistent with these motions to explain
      about 90% of the total variance of the system. These principal degrees of freedom
      represent slow anharmonic motional modes, clearly pointing at distinguished
      mobility of the atoms involved in the protein's functionality.

PMID- 10087498
TI  - Methodological developments and strategies for a fast flexible superposition of
      drug-size molecules.
AB  - An alternative to experimental high through-put screening is the virtual
      screening of compound libraries on the computer. In absence of a detailed
      structure of the receptor protein, candidate molecules are compared with a known
      reference by mutually superimposing their skeletons and scoring their similarity.
      Since molecular shape highly depends on the adopted conformation, an efficient
      conformational screening is performed using a knowledge-based approach. A
      comprehensive torsion library has been compiled from crystal data stored in the
      Cambridge Structural Database. For molecular comparison a strategy is followed
      considering shape associated physicochemical properties in space such as steric
      occupancy, electrostatics, lipophilicity and potential hydrogen-bonding.
      Molecular shape is approximated by a set of Gaussian functions not necessarily
      located at the atomic positions. The superposition is performed in two steps:
      first by a global alignment search operating on multiple rigid conformations and
      then by conformationally relaxing the best scored hits of the global search. A
      normalized similarity scoring is used to allow for a comparison of molecules with
      rather different shape and size. The approach has been implemented on a cluster
      of parallel processors. As a case study, the search for ligands binding to the
      dopamine receptor is given.

PMID- 10087499
TI  - Combinatorial docking and combinatorial chemistry: design of potent non-peptide
      thrombin inhibitors.
AB  - A computational algorithm was used to design automatically novel thrombin
      inhibitors that are available from a single-step chemical reaction. The compounds
      do not contain amide bonds, are achiral and have a molecular weight below 400. Of
      the 10 compounds that were synthesized, five bind to thrombin with a Ki in the
      nanomolar range. Subsequent X-ray structure determination of the thrombin
      inhibitor complex for the best compound (Ki = 95 nM) confirms the predicted
      binding mode. The novel algorithm is applicable to a broad range of chemical
      reactions.

PMID- 10087500
TI  - A computational model of the nicotinic acetylcholine binding site.
AB  - We have derived a model of the nicotinic acetylcholine binding site. This was
      accomplished by using three known agonists (acetylcholine, nicotine and
      epibatidine) as templates around which polypeptide side chains, found to be part
      of the receptor cavity from published molecular biology studies, are allowed to
      flow freely in molecular dynamics simulations and mold themselves around these
      templates. The resulting supramolecular complex should thus be a complement, both
      in terms of steric effects as well as electronic effects, to the agonists and it
      should be a good estimation of the true receptor cavity structure. The shapes of
      those minireceptor cavities equilibrated rapidly on the simulation time scale and
      their structural congruence is very high, implying that a satisfactory model of
      the nicotinic acetylcholine binding site has been achieved. The computational
      methodology was internally tested against two rigid and specific antagonists
      (dihydro-beta-erytroidine and erysoidine), that are expected to give rise to a
      somewhat differently shaped binding site compared to that derived from the
      agonists. Using these antagonists as templates there were structural
      reorganizations of the initial receptor cavities leading to distinctly different
      cavities compared to agonists. This indicates that adequate times and
      temperatures were used in our computational protocols to achieve equilibrium
      structures for the agonists. Overall, both minireceptor geometries for agonists
      and antagonists are similar with the exception of one amino acid (ARG209).

PMID- 10087501
TI  - Modelling of adrenoceptor ligand targets based on novel medium- or macro-sized
      fused nitrogen heterocyclic systems.
AB  - Novel medium- and macro-sized heterocyclic compounds were assessed for their
      potential as subtype-selective adrenergic ligands. Their conformational
      flexibilities were investigated and their geometric shapes were compared to rigid
      lead compounds of known selectivity. In the case of alpha 1A selective
      antagonists, interesting potential targets for synthesis and evaluation were
      identified by 'opening up' various rings of the fused-ring lead compound 1 by
      shared-bond cleavage. For alpha 2 selective ligands, compound 6 was the lead
      compound and the possibility of mimicking the fused-ring system via
      intramolecular hydrogen bonding was investigated. None of the potential targets
      were closely enough related in this case to the lead compound to warrant
      synthesis.

PMID- 10087502
TI  - A molecular-field-based similarity study of non-nucleoside HIV-1 reverse
      transcriptase inhibitors.
AB  - This article describes a molecular-field-based similarity method for aligning
      molecules by matching their steric and electrostatic fields and an application of
      the method to the alignment of three structurally diverse non-nucleoside HIV-1
      reverse transcriptase inhibitors. A brief description of the method, as
      implemented in the program MIMIC, is presented, including a discussion of
      pairwise and multi-molecule similarity-based matching. The application provides
      an example that illustrates how relative binding orientations of molecules can be
      determined in the absence of detailed structural information on their target
      protein. In the particular system studied here, availability of the X-ray crystal
      structures of the respective ligand-protein complexes provides a means for
      constructing an 'experimental model' of the relative binding orientations of the
      three inhibitors. The experimental model is derived by using MIMIC to align the
      steric fields of the three protein P66 subunit main chains, producing an overlay
      with a 1.41 A average rms distance between the corresponding C alpha's in the
      three chains. The inter-chain residue similarities for the backbone structures
      show that the main-chain conformations are conserved in the region of the
      inhibitor-binding site, with the major deviations located primarily in the
      'finger' and RNase H regions. The resulting inhibitor structure overlay provides
      an experimental-based model that can be used to evaluate the quality of the
      direct a priori inhibitor alignment obtained using MIMIC. It is found that the
      'best' pairwise alignments do not always correspond to the experimental model
      alignments. Therefore, simply combining the best pairwise alignments will not
      necessarily produce the optimal multi-molecule alignment. However, the best
      simultaneous three-molecule alignment was found to reproduce the experimental
      inhibitor alignment model. A pairwise consistency index has been derived which
      gauges the quality of combining the pairwise alignments and aids in efficiently
      forming the optimal multi-molecule alignment analysis. Two post-alignment
      procedures are described that provide information on feature-based and field
      based pharmacophoric patterns. The former corresponds to traditional
      pharmacophore models and is derived from the contribution of individual atoms to
      the total similarity. The latter is based on molecular regions rather than atoms
      and is constructed by computing the percent contribution to the similarity of
      individual points in a regular lattice surrounding the molecules, which when
      contoured and colored visually depict regions of highly conserved similarity. A
      discussion of how the information provided by each of the procedures is useful in
      drug design is also presented.

PMID- 10087503
TI  - Cell adhesion: more than just glue (review).
AB  - The ability of cells to interact with each other and their surroundings in a co
      ordinated manner depends on multiple adhesive interactions between neighbouring
      cells and their extracellular environment. These adhesive interactions are
      mediated by a family of cell surface proteins, termed cell adhesion molecules.
      Fortunately these adhesion molecules fall into distinct families with adhesive
      interactions varying in strength from strong binding involved in the maintenance
      of tissue architecture to more transient, less avid, dynamic interactions
      observed in leukocyte biology. Adhesion molecules are extremely versatile cell
      surface receptors which not only stick cells together but provide biochemical and
      physical signals that regulate a range of diverse functions, such as cell
      proliferation, gene expression, differentiation, apoptosis and migration. In
      addition, like many other cell surface molecules, they have been usurped as
      portals of entry for pathogens, including prions. How the mechanical and chemical
      messages generated from adhesion molecules are integrated with other signalling
      pathways (such as receptor tyrosine kinases and phosphatases) and the role that
      aberrant cell adhesion plays in developmental defects and disease pathology are
      currently very active areas of research. This review focuses on the biochemical
      features that define whether a cell surface molecule can act as an adhesion
      molecule, and discusses five specific examples of how cell adhesion molecules
      function as more than just 'sticky' receptors. The discussion is confined to the
      signalling events mediated by members of the integrin, cadherin and
      immunoglobulin gene superfamilies. It is suggested that, by controlling the
      membrane organization of signalling receptors, by imposing spatial organization,
      and by regulating the local concentration of cytosolic adapter proteins,
      intercellular and cell-matrix adhesion is more than just glue holding cells
      together. Rather dynamic 'conversations' and the formation of multi-protein
      complexes between adhesion molecules, growth factor receptors and matrix
      macromolecules can now provide a molecular explanation for the long-observed but
      poorly understood requirement for a number of seemingly distinct cell surface
      molecules to be engaged for efficient cell function to occur.

PMID- 10087504
TI  - Preliminary characterization of the protein encoded by human testis-enhanced gene
      transcript (TEGT).
AB  - TEGT is a conserved, widely expressed gene transcript of unknown function that
      has been studied previously only at the nucleic acid level. The deduced amino
      acid sequence predicts a highly hydrophobic, 26.5 kDa integral membrane protein
      with seven potential transmembrane domains. Little else is known about TEGT
      protein because of the lack of definitive homology to other known sequences and
      the absence of informative consensus motifs. The present report details a
      preliminary study of human TEGT (hTEGT) protein. (i) In vitro translation of
      hTEGT in reticulocyte lysates required the presence of microsomes for efficient
      synthesis, suggesting that hTEGT must target to the endoplasmic reticulum to be
      translated. Immunofluorescence of cells transiently expressing haemagglutinin
      tagged hTEGT localized the protein mainly to the endoplasmic reticulum. The
      protein demonstrated no obvious post-translational modifications such as signal
      peptide cleavage, N-linked glycosylation or O-linked glycosylation. (ii) Both
      hTEGT and haemagglutinin-tagged hTEGT appeared to retain partial secondary and
      tertiary structure in the presence of SDS. Both electrophoresed as a broad band
      or doublet with apparent molecular weights of 22-24.5 kDa on SDS-PAGE, aggregated
      either homotypically or heterotypically when boiled in SDS, and were toxic after
      24 h when highly overexpressed in 293 T cells. These properties are believed to
      be caused by the protein's hydrophobicity. (iii) The protein appeared to
      associate strongly with other intracellular molecules since haemagglutinin-tagged
      hTEGT was extracted poorly from transiently transfected HeLa cells. Further study
      will be required to determine the cellular function of TEGT.

PMID- 10087505
TI  - Short-term regulation of endothelial Na(+)-K(+)-pump activity by cGMP: a 133Cs
      magnetic resonance study.
AB  - The effect of nitric oxide radicals (NO) on the activity of porcine aortic
      endothelial Na(+)-K(+)-ATPase is reported. Measurements were made using an in
      vitro cell system and 133Cs magnetic resonance (NMR). It is shown that NO,
      through stimulation of guanylate cyclase, results in a reduction of pump
      activity. Similar observations were made using 8-Br-cGMP. Measurement of the
      cytosolic volume indicated no changes in volume during incubation with 8-Br-cGMP.
      Our measurements indicate a continuous regulation of endothelial Na(+)-K(+)
      ATPase activity by endogenous NO. This regulation could be removed by L-NAME,
      resulting in a small increase in pump activity.

PMID- 10087506
TI  - Characteristics of the osmotically induced membrane rupture.
AB  - The phenomenon of reciprocating mechanical oscillations of electrofused
      erythrocytes was used to investigate the mechanical characteristics of ruptures
      induced in erythrocyte membranes by colloid osmotic pressure. The rupture
      characteristics follow an exponentially decaying time function. Time constants
      determined for opening times of ruptures decreased from 5.5 ms at 10 degrees C to
      3.8 ms and 2.0 ms at 40 degrees C for the first and the last observable rupture,
      respectively. Evidence is given that the diameter of the membrane rupture exceeds
      the size of a haemoglobin molecule. With repetitive membrane rupturing, the
      ability of the membrane bilayer and associated structures to heal decreases,
      owing to the reduced ability to withstand pressure gradients. This change allows
      oscillating doublets to be classified according to one of three groups: group A
      showing no development in response to swell times, group B showing a continuous
      decrease in response to swell times, and group C showing a spontaneous decrease
      in response to swell times. These results suggest that oscillations cease as a
      result of defects of membrane healing. Calculations of respective temperature
      ranges are in agreement with temperature ranges for spectrin denaturation. Thus,
      conclusions obtained from this study suggest that the spectrin network plays a
      key role in membrane healing processes after mechanical membrane rupture.

PMID- 10087507
TI  - Molecular cloning, functional expression and chromosomal localization of a cDNA
      encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine
      nucleosides and uridine.
AB  - Two Na(+)-dependent nucleoside transporters implicated in adenosine and uridine
      transport in mammalian cells are distinguished functionally on the basis of
      substrate specificity: CNT1 is selective for pyrimidine nucleosides but also
      transports adenosine; CNT2 (also termed SPNT) is selective for purine nucleosides
      but also transports uridine. Both proteins belong to a gene family that includes
      the NupC proton/nucleoside symporter of E. coli. cDNAs encoding members of the
      CNT family have been isolated from rat tissues (jejunum, brain, liver; rCNT1 and
      rCNT2/SPNT) and, most recently, human kidney (hCNT1 and hSPNT1). Here, the
      molecular cloning and functional characterization of a CNT2/SPNT-type transporter
      from human small intestine are described. The encoded 658-residue protein (hCNT2
      in the nomenclature) had the same predicted amino acid sequence as human kidney
      hSPNT1, except for a polymorphism at residue 75 (Arg substituted by Ser), and was
      83 and 72% identical to rCNT2 and hCNT1, respectively. Sequence differences
      between hCNT2 and rCNT2 were greatest at the N-terminus. In Xenopus oocytes,
      recombinant hCNT2 exhibited the functional characteristics of a Na(+)-dependent
      nucleoside transporter with selectivity for adenosine, other purine nucleosides
      and uridine (adenosine and uridine K(m) app values 8 and 40 microM,
      respectively). hCNT2 transcripts were found in kidney and small intestine but,
      unlike rCNT2, were not detected in liver. Deoxyadenosine, which undergoes net
      renal secretion in humans, was less readily transported than adenosine. hCNT2
      also mediated small, but significant, fluxes of the antiviral purine nucleoside
      analogue 2',3'-dideoxyinosine. hCNT2 is, therefore potentially involved in both
      the intestinal absorption and renal handling of purine nucleosides (including
      adenosine), uridine and purine nucleoside drugs. The gene encoding hCNT2 was
      mapped to chromosome 15q15.

PMID- 10087508
TI  - Compensating lipid fluxes generated by the aminophospholipid translocase.
AB  - By a combined kinetic and thermodynamic model on the transbilayer dynamics and
      asymmetric distribution of lipids in the red blood cell, compensating lipid
      fluxes to the exoplasmic leaflet have been analysed, counterbalancing the active
      transport of aminophospholipids to the cytoplasmic monolayer by the
      aminophospholipid translocase. The compensating fluxes are assumed to be of
      passive nature generated by forces of lateral mechanical stress and of lipid
      concentration differences between the two monolayers. These forces are shown to
      be caused and maintained by the operation of the aminophospholipid translocase.
      Simulations reveal that a reduction of the compensating fluxes upon ATP-depletion
      can be attributed to the inhibition of the aminophospholipid translocase. Thus, a
      Mg(2+)- and ATP-dependence of the outward movement of phospholipid analogues in
      the plasma membrane of red blood cells can be expected independent of the
      existence and operation of an ATP-dependent 'floppase' activity.

PMID- 10087509
TI  - Amino acid sequences which promote and prevent the binding and membrane insertion
      of surface-active peptides: comparison of melittin and promelittin.
AB  - The temporal sequence of molecular events involved in the interactions of a
      number of related peptides with membranes are revealed using two complementary
      fluorescence techniques. Comparative studies are reported of the interactions of
      melittin, promelittin and a melittin analogue with trp-19 replaced with Ile and
      the n-terminal gly replaced with a trp residue, with phosphatidylcholine
      membranes. It is shown that the interaction of the n-terminal region of melittin
      rapidly binds and inserts into the body of the membrane with a rate constant of
      around 367 s-1. This is followed by a slightly slower membrane insertion of the
      trp-19 region with a rate constant of around 112 s-1. The positive charges of the
      melittin molecule then come into close proximity with the membrane with rate
      constants around 27 s-1. Finally, these charged regions insert into the
      hydrophobic core of the membrane with rate constants of about 0.3 s-1. The effect
      of incorporating net negative charge onto the membrane surface in the form of 15
      mole % phosphatidylserine, augments by about threefold, the binding of the
      charged domains of the melittin molecule. The observations of the melittin
      interactions are compared with the melittin-precursor protein, promelittin.
      Sections of the promelittin molecule are also found to bind and insert into the
      body of the phospholipid membrane, although nearly 30 times less rapidly than
      melittin. No charged sections of promelittin are found to insert into the
      membrane.

PMID- 10087510
TI  - Repair of BHK cell surface ganglioside GM3 after its degradation by extracellular
      sialidase.
AB  - Treatment of BHK fibroblasts with V. cholerae sialidase for 20 min caused the
      breakdown of about 70% of total cellular ganglioside GM3 and the production of an
      approximately equivalent amount of lactosylceramide. On removal of the enzyme, a
      slow resynthesis of GM3 from lactosylceramide was observed, equivalent to about 5
      6%/h of the degraded GM3. Resynthesis of degraded surface ganglioside has not
      previously been observed, but its magnitude is similar to previous measurements
      of the rate of protein resialylation after sialidase treatment. This suggests
      that resialylation of both lipid and protein is limited by vesicular transport of
      plasma membrane components through the trans-Golgi network [TGN] where
      sialyltransferase is thought to be localized. In contrast, resynthesis of
      sphingomyelin which has been degraded at the cell surface by exogenous
      sphinogomyelinase is about five times faster than resynthesis of GM3 and may
      involve non-vesicular transport of ceramide.

PMID- 10087511
TI  - The L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2): expression and
      regulation in rat lactating mammary gland.
AB  - The Na(+)-dependent L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2),
      were expressed in rat lactating mammary gland, but EAAC1 (EAAT3) was not. GLT-1
      expression in rat lactating mammary gland was constant in all the physiological
      situations studied; however, the GLAST expression is under tight regulation.
      Fasting for 24 h decreased the GLAST expression which returned to control values
      after refeeding. Weaning for 24 h produced a decrease in GLAST expression through
      a mechanism independent of prolactin deficiency. Resuckling for 6 h returned the
      expression of this transporter to control values. There is a correlation between
      the levels of GLAST (mRNA and protein) and the in vivo uptake of L-glutamate by
      the lactating mammary gland during the starvation/refeeding cycle and milk
      accumulation process.

PMID- 10087512
TI  - [Relationship between tics and compulsion].
AB  - In children and adolescents motor/vocal tics and obsessive-compulsive behavior
      are known to be closely related. Thereby, a continuum of symptoms ranging from
      single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to
      clinically relevant obsessions and compulsions could be described. As
      neurobiological substrates dysfunctions in corresponding cortico-striato
      thalamocortical circuits (sensorimotor circuit in tic symptomatology,
      orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both
      disturbances behavioral therapy can be used to improve control mechanisms to
      counterregulate tics and obsessive-compulsive behavior, respectively, and
      psychopharmacological agents can be administered to compensate dysbalances in
      neurotransmitter systems. In case of a mixed symptomatologic picture it is
      necessary to include interventions for both pols of the symptom-continuum in the
      therapeutic programme to achieve extensive improvement as a basis for a further
      positive development of the patient.

PMID- 10087513
TI  - [Current developments in the treatment of obsessive-compulsive disorders in
      children and adolescents].
AB  - For the treatment of obsessive-compulsive disorders during childhood and
      adolescence, multidimensional therapeutical approaches have proven useful in
      clinical practice. First controlled studies have demonstrated the efficacy of
      both psychotherapeutical and pharmacological strategies. Exposure and response
      prevention are considered the most efficient psychotherapeutical methods. On the
      basis of the available data, the question of the pharmacological dose can not be
      answered definitely. For Clomipramin, the dose most probably is between 75 mg and
      150 mg, where as for Fluoxetine and Fluvoxamine 20 mg-60 mg and 100 mg-250 mg
      respectively. However, it has to be kept in mind that sometimes improvement of
      symptoms is not seen after 8-10 weeks of treatment. Basically it can be stated
      that to date there is an urgent need for therapeutical studies of obsessive
      compulsive disorders in the childhood and adolescence. Most relevant would be
      studies evaluating pharmacological treatment versus a placebo control groups and
      carefully designed controlled psychotherapeutical treatment studies as well
      studies comparing pharmacological and psychotherapeutical approaches.

PMID- 10087514
TI  - [Assessment of the attention-deficit hyperactivity disorder in adults].
AB  - The attention-deficit hyperactivity disorder (ADHD) is one of the most common
      disorders in childhood and adolescence with a prevalence of app. 5%. The
      importance of ADHD in childhood as a factor of vulnerability for psychiatric
      disorders in adults is becoming a focus of discussion. It was shown that there is
      a comorbidity in adults with substance abuse, delinquency and personality
      disorders. There is a growing evidence that ADHD will persist in a significant
      number of patients during adulthood. This is the first german study to evaluate
      this interdependence. We examined 164 adult inpatients and 48 healthy volunteers
      with the Wender Utah Rating Scale (WURS), a retrospective self-evaluation scale
      for the diagnosis of ADHD in childhood, and the Eysenck impulsiveness
      questionnaire I7. It could be shown that the WURS and the I7 are suitable
      instruments for the evaluation of the ADHD in adults especially concerning the
      aspects of attention deficits and impulsiveness.

PMID- 10087515
TI  - [Stability and variability of catatonic symptoms in the longitudinal course of
      illness. Videotape documentation in catatonic schizophrenia].
AB  - The symptomatology of a female patient with catatonic schizophrenia is presented
      with respect to its longitudinal course. The stability and variability of
      catatonic symptoms are investigated using videotape technique. It is demonstrated
      that catatonic symptoms are stable in the longitudinal course but due to unsteady
      arousal the severity of the catatonic symptoms varies markedly. There are
      fluctuating symptom patterns that dominate the clinical picture: a hyperkinetic
      form with prevailing restlessness or excitement, with abnormal involuntary
      movements, stereotypies, and parakinetic movements, and a hypokinetic form with
      various inhibition phenomena, mutism and stupor. The clinical impression of the
      catatonic syndrome changes according to the dominating symptom patterns at
      different times, whereas the less severe symptoms recede into the background and
      thus, may be overlooked. Considering this finding the problem of a 'diagnostic
      threshold' is discussed. The authors intend to emphasize videotape documentation
      of catatonic motor disturbances as most useful. This technique may contribute to
      differentiating illness related from neuroleptic induced movement disorders.

PMID- 10087516
TI  - [Body weight regulation in anorexia nervosa with special attention to leptin
      secretion].
AB  - Underweight is a key symptom in anorexia nervosa. In this review we summarize
      recent findings pertaining to weight regulation in this eating disorder. The
      observation that a body mass index below 13 kg/m2 upon admission for inpatient
      treatment is associated with a high mortality rate and chronic persistence of
      underweight is of obvious clinical relevance. A lowered leptin secretion, which
      results from the weight loss, is presumably of major importance for the
      development of amenorrhea. We discuss findings pertaining to a reduced body
      weight in other psychiatric disorders during adolescence in the light of
      Kretschmer's findings related to body frame and psychopathology.

PMID- 10087517
TI  - [Quality of life. Construct validation and the development of a modular system].
AB  - The construct Quality of Life (QoL) is investigated by metaanalysis of eight
      (inter)nationally validated questionnaires in a multicenter study. Data have been
      collected in a mentally healthy (n = 479), a depressed (n = 171) and a
      schizophrenic (n = 139) sample. Conventional psychometric criteria and a facet
      analytical methodology have been applied. The resulting questionnaire "Modular
      System for Quality of Life" (MSQoL) consists of a core module with 47 items (one
      "G-factor" and six subdimensions), which is sufficiently valid for all three
      samples. Additionally, there are four specific modules (demography, family,
      partnership, profession). No specific modules can be identified for the
      psychopathological subgroups. The validated radex structure for subjective QoL
      offers the opportunity for a cumulative research design and for adaptations to
      the actual setting.

PMID- 10087518
TI  - [Management of mental health and primary care. Development and evaluation of a
      training program based on the PLISSIT approach].
AB  - Deficits in current approaches of psychosomatic and psychiatric education for
      general practitioners are reviewed. A skill-based training was developed in line
      with the four step counseling approach of the "PLISSIT" approach: The GP helps in
      first step ("permission") the patient to accept his problem and assesses
      informations about causing and maintaining factors of his symptomatology. In the
      second step he should provide information about the disorder and reverse
      misunderstanding and passivity (Limited Information). The GP's should develop
      preliminary strategies for change in the third step ("coping strategies",
      "symptom management", "special suggestions") and preparate the intensive phase of
      therapy as the last step. First results of the evaluation of the training program
      are presented demonstrate the effectiveness and acceptance of the education
      program.

PMID- 10087519
TI  - [Clozapine and obsessive-compulsive symptoms in schizophrenia. A case history of
      one patient].
AB  - In the examination in question, the case history of a patient who had exhibited
      serious obsessive-compulsive symptoms since the age of 14 is described. It is not
      an independent obsessive-compulsive disorder, but a case of schizophrenia masked
      by obsessive-compulsive symptoms. During therapy for the schizophrenic symptoms
      with clozapine, which set in at the age of 31, neither psychotic symptoms nor
      obsessive-compulsive symptoms worth mentioning can be found at the 1-year
      catamnesis. Whereas the literature increasingly points to obsessive-compulsive
      symptoms being a side-effect of clozapine medication, usually in the clinical
      indication area of chronic schizophrenic psychoses, as far as the author knows,
      this describes a rare case of improvement of obsessive-compulsive symptoms using
      clozapine after first suffering from a schizophrenic disorder. The meaning of
      differential diagnostics of obsessive-compulsive phenomena for adequate
      pharmacotherapy is discussed using the example of the individual case.

PMID- 10087520
TI  - [Olanzapine in the treatment of depressive disorders with psychotic symptoms].
AB  - We report on the successful treatment of two female patients with psychotic
      depression with the new atypical neuroleptic drug olanzapine. A 75-year-old
      female inpatient suffering from recurrent endogenous depression with tactile
      hallucinations and coenesthesia was refractory to a systematic sequential
      antidepressant treatment strategy during a 39-week period. After addition of the
      new atypical neuroleptic olanzapine to the SSRI citalopram, she showed immediate
      and ongoing symptom relief. In the second case of a 57-year-old female inpatient
      suffering from delusional depression, we observed marked symptom relief and
      correction of the delusions of impoverishment. Olanzapine is discussed with
      regard to its receptor-binding profile (antagonism to 5-HT2A- and D1-D4
      receptors) as a potential neuroleptic drug in the treatment of affective
      disorders with psychotic symptoms.

PMID- 10087521
TI  - [Dependency of non-benzodiazepine hypnotics. Two case reports].
AB  - With the introduction of the non-benzodiazepine hypnotics zopiclone and zolpidem
      it was expected to have hypnotics without side effects and risks
      characteristically seen with benzodiazepines. We report two cases with high-dose
      usage and dependency of non-benzodiazepine hypnotics. Both patients were
      prescribed the drugs to treat sleep disturbances occurring during a depressive
      episode. While one patient had a polysubstance abuse there was no evidence for an
      abuse history in the other patient. To reduce withdrawal symptoms long-acting
      benzodiazepines were given to both patients. Thus, it seems that not only
      patients with a history of substance abuse but also patients with a psychiatric
      disorder are at risk for abuse of non-benzodiazepine hypnotics. Considering the
      increasing number of case reports with abuse and dependence of zopiclone and
      zolpidem it seems necessary to reevaluate the dependency risk of the currently
      available non-benzodiazepine hypnotics.

PMID- 10087522
TI  - [Psychiatry and psychotherapy on the internet. Current overview].
AB  - The Internet is a fast growing medium, which is about to alter our all day life.
      Most impact is given to advantages of telemedicine to psychiatrists and
      psychotherapists as well as patients. After introduction of the essential
      features of the Internet practical aspects of medicine in Cyberspace for
      psychotherapists, psychiatrists and their patients are shown. Then, the general
      prohibition of advertisement for physicians is discussed on the bases of actual
      laws related to Internet activities. Relevant resources of medical information
      are shown with regard to the detailed facilities of using search engines.
      Highlighting opportunities and possible resources of medicine in cyberspace, it
      is made clear, that the rising interest in telemedicine on Internet is more than
      justified. Finally, some risks of virtual communication are visible. Important
      and mentioned Web-sites are listed at the end.

PMID- 10087524
TI  - [Value of functional imaging in Parkinson's disease and related movement
      disorders].
AB  - Modalities for imaging morphology do not contribute significantly to the
      differential diagnosis of movement disorders. In contrast, functional imaging as
      PET or SPECT can differentiate among Parkinson's disease (PD), vascular or toxic
      Parkinsonism and movement disorders within multi system degeneration. Especially
      the decreased DOPA uptake--detected by 18F-DOPA or 123I-beta CIT--within the
      striate with accentuation in the posterior putamen is typical for PD, where
      initially D2-receptor activity--imaged by 11C-raclopride or 123I-iodobenzamide-
      is increased. In contrast to this typical pattern dopaminergic terminals as well
      as D2-receptors are diffusely reduced in multi system degeneration, where often
      energy metabolism is additionally disturbed. In Parkinson syndrome of vascular
      origin focal disturbances of pre- and postsynaptic dopaminergic sites and energy
      metabolism are found, movement disorders after intoxication are accompanied by
      selective loss of dopaminergic neurons (MPTP) or by widespread neuronal damage in
      the basal ganglia as well as in the cortex (Cyanide, solvents). Functional
      studies additionally permit the follow-up of disease progression, by which also
      the efficacy of therapeutic strategies can be assessed.

PMID- 10087523
TI  - [Comments on the work of K. H. Krause et al. The hyperactive syndrome (attention
      deficit hyperactivity disorders) in adulthood. Nervenarzt (1998) 69: 543-556].

PMID- 10087525
TI  - [Treatment strategies for de novo Parkinson patients].

PMID- 10087526
TI  - [Combination therapy with lisuride and L-dopa in the early stages of Parkinson's
      disease decreases and delays the development of motor fluctuations. Long-term
      study over 10 years in comparison with L-dopa monotherapy].
AB  - A randomized, prospective study was carried out in order to investigate the
      efficacy of a dopamine agonist, lisuride, alone or in combination with levodopa,
      to minimize or postpone the development of motor fluctuations, compared with
      levodopa alone during 10 years' treatment of 90 patients with early Parkinson's
      disease. Only a small, and with time gradually decreasing number of patients
      obtained enough therapeutic benefit during long-term treatment with lisuride
      alone. Consequently, levodopa had to be added to the patients' regimen. During
      combined treatment with lisuride and levodopa the daily dose of levodopa needed
      for optimal therapeutic response was significantly lower than when using levodopa
      alone. The addition of levodopa to the lisuride regimen either from the beginning
      or at any time during long-term treatment according to clinical need, resulted in
      a therapeutic response in parkinsonian disability equal to that achieved with
      levodopa alone, but significantly decreased and postponed the development of
      motor fluctuations, end-of-dose failure and dyskinesias. Severe dopaminergic
      adverse events leading to withdrawal of the treatment were more frequent during
      treatment with lisuride and levodopa than with levodopa alone, but the lower
      mortality rate did not reach the level of statistical significance. In
      conclusion, according to the results obtained, it seems reasonable to consider a
      treatment strategy in early Parkinson's disease using a dopamine agonist, like
      lisuride, as the primary treatment and to delay the addition of levodopa until
      parkinsonian disability cannot be adequately controlled by a dopamine agonist.

PMID- 10087527
TI  - [Autonomic disturbances in Parkinson's disease and their treatment].
AB  - Disturbances of autonomic functions are, without a doubt, part of the
      symptomatology of Parkinson's disease, but do have little importance as initial
      symptoms. They are more prominent in the advanced stages of the disease, when
      they then have an impact on the kind of patients' complaints and on the effects
      of the therapeutic measures. For example, pollakisuria and urge incontinence are
      restrictive for social activities and, simultaneously, nighttime akinesia
      disturbs sleep and recovery. Dysfunction of gastrointestinal mobility brings
      about a retardation in drug transport from the stomach to the upper intestine and
      thereby in drug absorption with the sequel of an inadequate response of the
      parkinsonian symptomatology. Detailed registration--there is a large number of
      methods--of autonomic functions provides insight into the extent of the
      degenerative process, but mainly helps to find ways to improve the resulting
      dysfunctions. Whereas some signs like thermoregulation, sebaceous secretion and
      sleep disturbances caused by night-time akinesia do improve under drug treatment,
      others like cardiovascular dysregulation and delayed colon transit-time may even
      be worsened.

PMID- 10087528
TI  - [Multisystem degenerative diseases with Parkinsom syndrome. Differential
      diagnosis and differential therapeutic aspects].

PMID- 10087529
TI  - Serotonin stimulates migrating myoelectric complex via 5-HT3-receptors dependent
      on cholinergic pathways in rat small intestine.
AB  - We have investigated the effect of 5-hydroxytryptamine (5-HT) and different 5-HT
      receptor antagonists and atropine on the migrating myoelectric complex in the rat
      small intestine. Infusion of 5-HT dose-dependently shortened the interval between
      phase III of the migrating myoelectric complex (MMC). In untreated animals the
      interval in upper jejunum was 19.1 (16.0-22.1) min. At doses of 10 and 20 nmol kg
      1 min-1, the interval decreased to 15.2 (12.0-18.4) and 10.2 (9.4-11.0) min,
      respectively. The 5-HT3-receptor antagonist ondansetron (0.5 mg kg-1) alone
      increased the MMC interval from 20.8 (15.1-26.5) to 33.9 (19.4-48.4) min. Neither
      methiothepin (0.5 mg kg-1) nor ketanserin (0.5 mg kg-1), selective for 5-HT1/5
      HT2- and 5-HT2-receptors, respectively, changed the MMC interval. The 5-HT4
      receptor antagonist GR 113808 (0.5 mg kg-1) disrupted the MMC and induced
      irregular spiking activity. Ondansetron and atropine antagonized the 5-HT-induced
      shortening of the MMC interval. Neither methiothepin nor ketanserin affected the
      response to 5-HT. GR 113808 did not block the response to 5-HT in half of the
      animals; however, in the remaining ones MMC was disrupted and irregular spiking
      induced. In conclusion, these results show that 5-HT dose-dependently stimulates
      the cycling of the MMC in the small intestine via 5-HT3-receptors and a
      cholinergic final pathway. Our findings encourage further studies on the role of
      the 5-HT3-receptor in the control of gastrointestinal motility.

PMID- 10087530
TI  - Dysmotility of the small intestine in achalasia.
AB  - During recent years there has been increasing evidence for extraoesophageal
      dysfunction in achalasia. The aim was to investigate whether motility of the
      small intestine is abnormal in achalasia. Thirteen patients (eight men, five
      women) aged 52 (33-85) years were studied. They had all previously undergone
      treatment with pneumatic balloon dilatation and were free of dysphagia when
      examined. Ambulatory 24-h motility was recorded in the upper jejunum under
      standardized caloric intake with a digital datalogger and catheter-mounted
      pressure transducers located beyond the ligament of Treitz. Visual analysis was
      performed by two observers and data underwent quantitative analysis of phasic
      contractile events using a computer program. Normal values were obtained from 50
      healthy controls. In the fasting state, a complete loss of cyclic MMC activity (n
      = 2), an abnormally prolonged phase II (n = 2) and disturbances in the aboral
      migration of phase III (n = 5) were observed. Postprandial motor response was
      absent (n = 2) or frequently showed a contraction frequency below the normal
      range (n = 5). Further abnormalities consisted in hypomotility during phase II (n
      = 3) and in a reduced frequency of migrating clustered contractions in the
      fasting (n = 2) or postprandial state (n = 2). In addition, motor events not
      present in any healthy subject, giant migrating contractions (n = 5), retrograde
      clustered contractions (n = 6) and repetitive retrograde contractions (n = 3)
      were identified. Each patient exhibited findings out of the range of normal.
      Dysmotility of the proximal small intestine is present in achalasia.

PMID- 10087531
TI  - Validation of antroduodenal motility measurements made by echo-planar magnetic
      resonance imaging.
AB  - Echo planar imaging, a development of magnetic resonance imaging, can produce
      snapshot images of the stomach and antroduodenal segment in as little as 64 msec
      and can be more useful than conventional techniques when assessing motility. The
      aim of this study was to compare antroduodenal motility measured by simultaneous
      perfused tube manometry and echo planar imaging. Ten volunteers were studied
      following the ingestion of 500 mL water or 500 mL porridge. Antroduodenal images,
      with acquisition times of 130 msec, were taken at 3-sec intervals, synchronized
      with motility traces and presented as a split-screen video. This allowed direct
      visual comparison of gastric wall movement and motility to be made. Contractions
      were confined to either the stomach or the duodenum or propagated across the
      antroduodenal segment. Over 4550 images were available for analysis. A larger
      number of propagated contractions were recorded with echo planar imaging in both
      water (P = 0.03) and food (P = 0.02) groups, whereas manometry detected a greater
      number of isolated duodenal pressure waves (P = 0.005). The contraction rate for
      water and food studies was similar, but direct visualization indicated that the
      manometric technique under-detected propagated events. The ability of echo planar
      imaging to record antroduodenal contractile activity provides a new insight into
      the role of occlusive and nonocclusive contractions during gastric emptying.

PMID- 10087532
TI  - Fat delays emptying but increases forward and backward antral flow as assessed by
      flow-sensitive magnetic resonance imaging.
AB  - Flow has been assessed in the gastric antrum using a velocity-sensitive version
      of the high-speed magnetic resonance imaging technique, echo planar imaging
      (EPI). Eight healthy volunteers attended fasted on three separate days and
      consumed 800 mL of either a 5% glucose (0.2 kcal mL-1), 10% glucose (0.4 kcal mL
      1) or an isotonic mixed nutrient meal, Fresubin (1 kcal mL-1, 27.2 g fat).
      Gastric volumes were obtained at 10-min intervals for 1 h. Flow measurements were
      performed on a single slice through the antropyloric region 5 and 35 min after
      meal ingestion. Gastric volumes at 45 min were inversely proportional to the
      calorie density of the meal with (mean +/- SEM) 89 +/- 10%* of the Fresubin, 64
      +/- 5%* of the 10% glucose and 41 +/- 5% of the 5% glucose remaining (*P < 0.005
      vs 5% glucose). Substantial forward and backward antral flow was observed after
      all three meals in the initial 5-min imaging period. AT 35 min flow activity was
      significantly greater after both the high-calorie meals relative to the 5% meal
      (total number of flow events: Fresubin = 6.6 +/- 1.7,[symbol: see text] 10%
      glucose = 9.9 +/- 2.2, [symbol: see text] 5% glucose = 2.5 +/- 0.9,[symbol: see
      text] P < 0.03,[symbol: see text] P < 0.007 vs 5% glucose, n = 8). Peak forward
      velocities for the initial phase of emptying tended to be greater for the rapidly
      emptying 5% meal (5.9 +/- 0.8 cm-1) compared with the Fresubin (3.3 +/- 0.6 cm-1,
      P < 0.069, n = 8) and the 10% glucose (2.9 +/- 1.0 cm-1, P < 0.068, n = 8) meals.
      In spite of delayed gastric emptying, high-calorie meals were associated with
      substantial to and fro movements which may be important for meal tritruration and
      fat emulsification.

PMID- 10087533
TI  - Cognitive evoked potentials to anticipated oesophageal stimulus in humans:
      quantitative assessment of the cognitive aspects of visceral perception.
AB  - Evoked potential studies provide an objective measure of the neural pathways
      involved with perception. The effects of cognitive factors, such as anticipation
      or awareness, on evoked potentials are not known. The aim was to compare the
      evoked potential response to oesophageal stimulation with the cortical activity
      associated with anticipation of the same stimulus. In 12 healthy men (23.5 +/- 4
      years), oesophageal electrical stimulation (15 mA, 0.2 Hz, 0.2 msec) was applied,
      and the evoked potentials recorded using scalp electrodes. A computerized model
      of randomly skipped stimuli (4:1 ratio) was used to separately record the evoked
      potentials associated with stimulation and those associated with an anticipated
      stimulus. The electrical stimulus represented the nontarget stimulus and the
      skipped impulse the target (anticipatory) stimulus. This anticipatory evoked
      potential was also compared to auditory P300 evoked potentials. Reproducible
      evoked potentials and auditory P300 responses were elicited in all subjects.
      Anticipatory evoked potentials (peak latency 282.1 +/- 7.9 msec, amplitude 8.2 +/
      0.7 microV, P < 0.05 vs auditory P300 evoked potential) were obtained with the
      skipped stimulus. This anticipatory evoked potential was located frontocentrally,
      while the auditory P300 potential was located in the centro-parietal cortex. The
      anticipatory evoked potential associated with expectation of an oesophageal
      stimulus, although of similar latency to that of the auditory P300 evoked
      response, originates from a different cortical location. The recording of
      cognitive evoked potentials to an expected oesophageal stimulus depends on
      attention to, and awareness of, the actual stimulus. Anticipatory evoked
      potentials to GI stimuli may provide an objective electrophysiological tool for
      the assessment of the cognitive factors associated with visceral perception.

PMID- 10087534
TI  - Effect of somatostatin on human gallbladder motility: an in vitro study.
AB  - In vivo studies have demonstrated that somatostatin induces human gallbladder
      relaxation. To determine whether this polypeptide acts directly on the
      gallbladder muscle, its effect on strips of human gallbladder was studied in
      vitro. Strips of gallbladder were set up isometrically in an organ bath
      containing oxygenated Krebs' solution. Dose-response curves to cholecystokinin
      octapeptide and carbachol were first established. The ability of somatostatin to
      cause relaxation under basal conditions and during 50% maximal stimulation by
      cholecystokinin-octapeptide (7.2 x 10(-8) M) and carbachol (3.5 x 10(-6) M) was
      assessed in 32 strips at 4.3 x 10(-6) M concentration which mimics the plasma
      concentrations found in patients with somatostatinoma and in 12 additional strips
      at 4.3 x 10(-8) M concentration. Somatostatin action on the intrinsic innervation
      by using electrical field stimulation (EFS) (200 mA 5 msec in duration, 30 Hz;
      400 mA, 1 msec in duration, 10 Hz) was also evaluated in 39 strips. Somatostatin
      had no effect on the basal or carbachol-generated tensions. On the contrary,
      somatostatin (4.3 x 10(-6) M) reduced cholecystokinin-octapeptide-generated
      tensions by 8% (P < 0.001) and reduced EFS-generated tensions at 30 Hz by 7.7% (P
      < 0.01) and those at 10 Hz by 41.2% (P < 0.01). All responses to cholecystokinin
      octapeptide and carbachol were abolished by dibutyryl-guanosine 3', 5'-cyclic
      monophosphate (5 x 10(-3) M) and atropine (10(-5) M), respectively (P < 0.0002
      and P < 0.0002). All responses to electrical field stimulation were reduced or
      abolished by tetrodotoxin (2 x 10(-6) M) (P < 0.001 and P < 0.0001,
      respectively). Our findings show that somatostatin exerts its inhibitory action
      on the response to cholecystokinin-octapeptide and on the intrinsic innervation
      of the gallbladder smooth muscle. The probable neurotransmitter is the
      acetylcholine.

PMID- 10087535
TI  - Altered myoelectrical activity in noninflamed ileum of rats with colitis induced
      by trinitrobenzene sulphonic acid.
AB  - Changes in gastric emptying and orocaecal transit time in patients with
      ulcerative colitis suggest that disturbances in gut motility may not be
      restricted to inflamed sites. This study sought to characterize changes in the
      motility of noninflamed ileum in a rat colitis model and to explore the
      mechanism(s) potentially involved. The myoelectrical activity of the ileum was
      recorded in rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis. The
      degree of ileal and colonic inflammation was assessed by quantification of
      macroscopic damage and myeloperoxidase activity (MPO). The effect on ileal
      motility of pretreatment with atropine, indomethacin and NG-nitro-L-arginine
      methyl ester (L-NAME) was investigated. TNBS-induced inflammation was restricted
      to the distal colon, as evidenced by morphological scores and MPO. Colitis was
      associated with increased frequency of ileal migrating motor complexes,
      characterized mainly by a decrease in the duration of phases I and III. The
      occurrence of ileal giant migrating complexes remained unchanged. The
      myoelectrical changes observed in the ileum persisted after treatment with
      atropine, indomethacin and L-NAME. Distal colitis is associated with abnormal
      myoelectrical activity in the noninflamed ileum of rats. Neither acetylcholine
      nor prostaglandins and nitric oxide seem to be involved.

PMID- 10087536
TI  - Alteration of swallowing and oesophageal peristalsis by different initiators of
      deglutition.
AB  - It has long been believed that once initiated, the involuntary phase of
      deglutition follows a stereotypical pattern, that is modified only by ongoing
      sensory input from the transported bolus. To test the hypothesis that the mode of
      sensory activation of deglutition can modify the motor response irrespective of
      bolus characteristics, the mylohyoid, lower oesophageal sphincter (LES) and
      oesophageal body response to swallows induced in anaesthetized opossums by
      pharyngeal stroking or superior laryngeal nerve (SLN) stimulation (unilateral and
      bilateral) were compared. In comparison with unilateral SLN stimulation, swallows
      triggered by pharyngeal stroking resulted in a greater mylohyoid spike burst and
      LES relaxation. There was no significant difference in the oesophageal and LES
      motor response to pharyngeal stroking vs bilateral SLN stimulation, although the
      mylohyoid response was of greater magnitude with pharyngeal stroking. These
      studies demonstrate that the motor component of deglutition can be altered by
      different sensory initiators of swallowing, and provides a possible link between
      oropharyngeal and oesophageal motor disorders.

PMID- 10087537
TI  - Hyperthermia prevents functional, histological and biochemical abnormalities
      induced during ileitis.
AB  - Inflammatory bowel disease is associated with altered intestinal motility and
      epithelial damage. Hyperthermia induces heat shock protein expression, components
      of a basic cellular defence mechanism, and consequently prevents ischaemic
      damage. Here we investigate whether hyperthermia may prevent altered smooth
      muscle function as well as underlying inflammation in a model of inflammatory
      bowel disease. Ileal heat shock protein expression was induced in rats by
      hyperthermic shock (41.5 degrees C; 5 min). Two hours after heating or sham
      treatment, ileitis was evoked by TNBS. Ileal samples were taken 4 h later to
      determine the contractile response of circular muscle strips, and to measure heat
      shock protein expression, LTB4 generation and damage/inflammation. Ileitis was
      associated with an increase in the contractile response of circular muscle to
      substance P but not neurokinin A or nerve stimulation. Hyperthermia induced heat
      shock protein expression and also prevented this functional change as well as
      TNBS-induced LTB4 production, subsequent infiltration of neutrophils and
      epithelial damage. Thus, intestinal inflammation is associated with alterations
      in tachykinergic control of smooth muscle as well as inflammatory changes.
      Hyperthermia prevents these changes and induces heat shock protein expression.
      Pharmacological induction of these proteins may offer a novel clinical strategy
      in treating both of these aspects of disease.

PMID- 10087538
TI  - AVNRT: "what goes around, comes around"--but where?

PMID- 10087539
TI  - Modification of antegrade slow pathway is not crucial for successful catheter
      ablation of common atrioventricular nodal reentrant tachycardia.
AB  - We tested the hypothesis that in some patients affected by typical AVNRT,
      successful catheter ablation treatment may be achieved independently of specific
      measurable electrophysiological modifications of antegrade AV node conducting
      properties. Standard electrophysiological parameters and comparable antegrade AV
      node function curves were obtained, before and after successful ablation, in 104
      patients (mean age 52 +/- 16 years; 69 women and 35 men) affected by the common
      form of AVNRT. The end point of the ablation procedure was noninducibility of
      AVNRT and of no more than one echo beat. For the purpose of this study, AV node
      duality was defined as an increase of > or = 50 ms in the A2H2 interval in
      response to a 10 ms decrease of the A1A2 coupling interval. Before ablation, AV
      node duality was present in 65 patients (62%) and absent in 39 patients (37%).
      Ablation caused measurable modifications of electrophysiological properties of
      the AV node in most patients with elicited AV node duality, but not in most
      patients without demonstrable AV node duality. After ablation, AV node duality
      persisted in 20 patients who had it before, whereas a new duality that could not
      be elicited before appeared in 5 patients. During 19 +/- 6 months of follow-up,
      clinical AVNRT recurred in 1 of 45 patients who had disappearance of AV node
      duality after ablation, in 1 of 34 patients who did not show AV node duality
      before and after ablation, and in 1 of 20 patients who had persistence of AV node
      duality after ablation. In conclusion, modifications of antegrade conduction
      properties of the AV node are not crucial for the cure of AVNRT in many patients.

PMID- 10087540
TI  - Isoproterenol induced cardiovascular hypersensitiviy in nonpheochromocytoma
      patients with paroxysmal hyperadrenergic symptoms.
AB  - The objective of this study was to determine whether graded isoproterenol
      infusion test identifies a specific hypersensitivity response of the LV diastolic
      relaxation properties in nonpheochromocytoma patients with paroxysmal symptoms of
      hyperadrenergic surges. We hypothesized that patients with hyperadrenergic
      surges, not due to pheochromocytoma, have hypersensitivity of cardiac beta
      adrenergic receptor responses to exogenous catecholamines, resulting in
      enhancement of LV relaxation. We assessed the physiological beta 1 and beta 2
      receptor responsiveness to graded isoproterenol infusion (0.01, 0.02, 0.03 and
      0.04 microgram/kg per min) in 32 patients presented with hyperadrenergic surges
      not due to pheochromocytoma. Two major observations were made. First, systemic
      hemodynamic evaluation using 99m Technetium first pass method revealed
      hyperkinetic state only in 21 patients (20 females and 1 male; aged 31 +/- 9
      years); the other 11 patients were without hyperkinetic circulatory state (10
      females and 1 male; aged 41 +/- 9 years). At baseline, plasma catecholamines were
      not significantly different between the two groups. The baseline corrected LV
      peak filling and ejection rates (cPFR and cPER) were significantly higher in
      hyperkinetic group (cPFR: 10 +/- 2 vs 8 +/- 2 x 10(-2) Hz/ms, P = 0.03; cPER: 11
      +/- 2 vs 8 +/- 1 x 10(-2) Hz/ms, P = 0.002) and their baseline HR was faster (85
      +/- 16 vs 70 +/- 9 beats/min, P = 0.006). Second, the cardiac and vascular
      responses to isoproterenol infusion were compared between these two groups.
      During the graded isoproterenol infusion, the response of HR, systolic, and
      diastolic BP were not significantly different between the two groups at all doses
      of isoproterenol, but cPFR and cPER had a more marked response to the lowest dose
      of 0.01 mg/kg per min in the hyperkinetic group. Thus, the graded isoproterenol
      infusion test can differentiate between two groups of nonpheochromocytoma
      patients presenting with paroxysmal symptoms of hyperadrenergic surges. Only
      patients with baseline hyperkinetic hemodynamic profile had accentuated cardiac
      hyperresponsiveness to a low dose of isoproterenol. We concluded that cPFR and
      cPER is a more sensitive index to assess the response to isoproterenol, because
      of metabolic determinants affecting the rate of change in LV volume.

PMID- 10087541
TI  - Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic
      syncope: midodrine as second line treatment in patients refractory to beta
      blockers.
AB  - Pharmacological therapy of neurocardiogenic syncope is often limited by the
      relatively low response rate to such treatment. In particular, response to beta
      blocker treatment has been reported to average 50%. Therefore, a two-step
      protocol, with metoprolol being the drug of first choice, was developed and
      prospectively evaluated in consecutive patients with a history of repeated
      syncopal attacks and a positive tilt table test indicative of neurocardiogenic
      syncope. Patients not responding to the beta-blocker were switched to the alpha
      adrenoceptoragonist midodrine. Acute drug efficacy was assessed by repeated tilt
      table testing. The incidence of syncope recurrence rate was determined during a 7
      month follow-up. In 16 of 30 (53%) patients, metoprolol was primarily effective;
      this was also the case in 7 of 11 patients receiving midodrine. Thus, the overall
      efficacy rate could be increased to 77% by the treatment protocol (P = 0.009, as
      compared to beta-blocker treatment alone). During follow-up, only 1 of 27
      patients (4%) had a syncopal event. Thus, the two-step treatment protocol
      presented in this study proved to be safe and to improve significantly patients
      clinical symptoms, as well as results of repeated tilt table testing as compared
      to beta-blocker treatment alone.

PMID- 10087542
TI  - Plasma brain natriuretic peptide as a biochemical marker for atrioventricular
      sequence in patients with pacemakers.
AB  - We hypothesized that plasma brain natriuretic peptide, like plasma atrial
      natriuretic peptide, may reflect hemodynamic changes elicited by different
      cardiac pacing modes. The aim of this study was to investigate whether plasma
      brain natriuretic peptide could be influenced by different pacing modes or
      electrical stimulation. The subjects consisted of 164 patients with permanent
      pacemakers (52 VVI, 30 AAI, 82 DDD pacemakers) and unimpaired heart function.
      Patients with atrial fibrillation or spontaneous beats were excluded. Plasma
      atrial natriuretic peptide and brain natriuretic peptide levels were measured at
      a rate of 70 beats/min after 45 minutes in the supine position. Under ECG
      monitoring, the pacing mode was switched from DDD to VVI in 12 patients and from
      DDD to AAI in 4 patients with a dual chamber pacemaker. Plasma atrial natriuretic
      peptide and brain natriuretic peptide levels were also measured 30 minutes, 60
      minutes, and 1 week after mode switching. Plasma atrial natriuretic peptide and
      brain natriuretic peptide levels were significantly higher in the
      nonphysiological pacing group than in the physiological pacing group, whereas
      these values were similar in the DDD and AAI pacing groups. One week after
      switching from DDD to VVI, plasma atrial natriuretic peptide and brain
      natriuretic peptide levels were significantly increased, however no significant
      changes were observed after switching to AAI. Based on a multivariate regression
      analysis of noninvasive clinical parameters, only a low plasma brain natriuretic
      peptide was significantly correlated with physiological pacing. We conclude that:
      (1) plasma brain natriuretic peptide, like atrial natriuretic peptide, is
      influenced by the pacing mode, but is not influenced by electrical stimulation;
      and (2) low plasma brain natriuretic peptide is important in relation to
      physiological pacing.

PMID- 10087544
TI  - Is ventricular fibrillation interval an indicator of electrical defibrillation
      threshold?
AB  - To clarify whether peak-to-peak interval of the fibrillation wave (VF interval)
      during VF is an independent indicator of defibrillation efficacy, we measured the
      transcardiac DFT, VF intervals of the surface and local ECGs (lead II and the
      right ventricle), and the ERP in 82 open-chest dogs. Both VF intervals showed a
      negative correlation with heart weight (surface: r = -0.358 [P < 0.005]; local; r
      = -0.349 [P < 0.005]). DFT was 2.0 +/- 0.7 A and positively correlated with heart
      weight (r = 0.453 [P < 0.0001]). ERP did not show a significant correlation with
      heart weight. DFT was negatively correlated with VF interval (vs surface VF
      interval: r = -0.568 [P < 0.0001]; vs local VF interval: r = -0.504 [P <
      0.0001]), but showed only a weak negative correlation with ERP (r = -0.314 [P <
      0.005]). Even after allowing for the dependency of DFT and VF intervals on heart
      weight (normalized to a 100-g heart), the correlation between VF interval and DFT
      was still significant (vs surface VF interval: r = -0.487 [P < 0.0001]; vs local
      VF interval: r = -0.414 [P < 0.0002]). These results suggest that VF interval is
      an indicator of DFT in intact hearts that have not received pharmacological
      intervention.

PMID- 10087543
TI  - Rate dependent effects of procainamide on the threshold current for pacing in the
      setting of postrepolarization refractoriness in dogs.
AB  - Normally, ventricular APD exceeds the VERP. However, under specific circumstances
      this relation may change and can become inverse. This phenomenon of
      postrepolarization refractoriness may be caused by a decrease in excitability.
      The threshold current (TC) for pacing has never been quantified as a possible
      explanation for these observations. Using a MAP pacing catheter in the right
      ventricular apex, the rate dependent behavior of TC, VERP, and APD before and
      after procainamide (dose 20 mg/kg in 10 min + 5 mg/min infusion) was determined
      in 17 dogs with chronic complete AV block. Initially, TC was determined with 0.1
      mA accuracy. Using a pacing current of at least twice TC, VERP and APD showed a
      similar, rate dependent shortening for PCLs 800, 575, and 350 ms. Procainamide
      treatment led to an equal, rate independent VERP and APD increase: no post
      repolarization refractoriness. Subsequently, accuracy for TC determination was
      increased to 0.01 mA. Comparing PCLs 800 and 250 ms, TC doubled from 0.05 +/-
      0.01 to 0.10 +/- 0.09 mA during control and almost tripled from 0.06 +/- 0.02 to
      0.17 +/- 0.10 mA (P < 0.05) after procainamide. Using a fixed pacing current of
      exactly twice TC found at 800 ms PCL during control, VERP exceeded APD after
      procainamide treatment at 300 and 250 ms PCL: postrepolarization refractoriness.
      Increasing the pacing current to twice the rate dependent TC, the relation
      between VERP and APD normalized: no postrepolarization refractoriness. We
      conclude that after procainamide, rate dependent TC increase is of major
      importance for the phenomenon of postrepolarization refractoriness.

PMID- 10087545
TI  - Efficacy and safety of clonazepam in refractory neurally mediated syncope.
AB  - Neurally mediated syncope is a complex syndrome that is often difficult to manage
      using currently available treatment strategies. The efficacy and safety of
      clonazepam was evaluated in 35 patients with refractory neurally mediated
      syncope. All patients had syncope (n = 33) or disabling presyncope (n = 2) and a
      positive head-up tilt table test (HUTT) despite treatment with one or more of the
      following therapies: beta-blocker, high-salt diet, fludrocortisone, elastic
      compression stockings, and disopyramide. Clonazepam was initiated at 0.5 mg/day
      and titrated in 0.25-0.5 mg/day increments for symptom control. Early (first 8
      weeks) symptomatic response was achieved in 31 of 35 (89%) patients. Early HUTT
      reverted to negative in 29 of 35 (83%) patients. Two patients discontinued
      clonazepam during early follow-up due to side effects. Thirty-three patients
      received long-term clonazepam therapy. Twenty-five patients had late HUTT with 21
      remaining negative. Of the eight patients who did not have late HUTT, one patient
      discontinued clonazepam prior to HUTT due to side effects. Seven patients refused
      late HUTT. All seven patients achieved symptomatic control on clonazepam with two
      requiring dose titration. Of the 21 patients with a negative late HUTT, 18
      achieved symptomatic control with two of these patients requiring dose titration.
      Two patients who had only partial symptom control despite dose titration achieved
      total symptomatic control with the addition of disopyramide and beta-blockers.
      Two patients with a negative late HUTT discontinued clonazepam due to side
      effects. One patient had been symptomatically controlled while the other had
      recurrent symptoms with dose limiting side effects occurring after clonazepam
      dose titration. In the 4 patients with a positive late HUTT, 2 patients were
      symptomatically controlled, 1 patients required combination therapy with a beta
      blocker to achieve symptomatic control, and 1 patient discontinued therapy due to
      side effects. Overall, 29 of 35 (83%) patients continue to receive clonazepam
      with symptom control. Based on intention-to-treat HUTT results, 21 of 35 (60%)
      patients were responders. Four patients required clonazepam dose titration and
      three required combination therapy with clonazepam plus disopyramide and/or a
      beta-blocker to achieve control. Clonazepam was discontinued in 6 patients, 5 for
      side effects and 1 following a transient ischemic attack. Clonazepam appears to
      be an effective therapeutic alternative in patients with refractory neurally
      mediated syncope. Based on our preliminary findings, a placebo controlled
      evaluation of clonazepam in neurally mediated syncope is warranted.

PMID- 10087546
TI  - Performance of temporary epicardial stainless steel wire electrodes used to treat
      atrial fibrillation: a study in patients following open heart surgery.
AB  - AF is the most common arrhythmia following open heart surgery. Transthoracic
      cardioversion is used when pharmacological treatment fails to restore SR, or is
      ineffective in controlling ventricular response rate. We report on the
      performance of temporary atrial defibrillation wire electrodes implanted on the
      epicardium of patients undergoing open heart surgery. Epicardial stainless steel
      wire electrodes for both pacing/sensing and atrial defibrillation were placed at
      the left and right atrium during open heart surgery in 100 consecutive patients
      (age 65 +/- 9 years; male/female 77/23). Electrophysiological studies performed
      postoperatively revealed a test shock (0.3 J) impedance of 96 +/- 12 omega
      (monophasic) and 97 +/- 13 omega (biphasic). AF was induced by burst stimulation
      in 84 patients. All patients were successfully converted to SR. The mean energy
      of successful shocks was 3.1 +/- 1.9 J. Atrial pacing and sensing were
      accomplished in all patients. Pacing threshold was 1.9 +/- 1.7 V (0.5 ms) in the
      left atrium and 2.1 +/- 2 V in the right atrium. P wave sensing was 2.5 +/- 1.6
      mV in the left atrium and 2.3 +/- 1.4 mV in the right atrium. No complications
      were observed with shock application, nor with lead extraction. Atrial
      defibrillation using temporary epicardial wire electrodes can be performed
      successfully and safely in patients following cardiac operations. The shock
      energy required to restore SR is low. Electrical cardioversion in the absence of
      anesthesia should be feasible.

PMID- 10087547
TI  - Hemodynamic effect of rapid atrial pacing in fetal lambs.
AB  - To determine the threshold at which rapid atrial pacing brings on fetal
      circulatory failure, we made a fetal supraventricular tachyarrhythmia model and
      measured the central venous pressure, aortic pressure, and right and left
      ventricular outputs in five fetal lambs. Under maternal anesthesia, the uterus
      was opened, and under local anesthesia, polyvinyl catheters were inserted into
      the fetal superior vena cava and ascending aorta through a neck incision. Pacing
      leads (Medtronic model 6492) were then sutured onto the fetal right atrial
      appendage via right thoracotomy. Ventricular output was estimated using a Toshiba
      SSH-65A echocardiography by a transuterine approach. Fetal hemodynamics were
      observed without pacing (control), and at the atrial pacing rates of 200, 300,
      350, and 400/min. Central venous pressure (CVP) increased and the aortic pressure
      decreased when the right atrium was paced at 350/min or more. Right ventricular
      output decreased when the right atrium was paced at 300/min or more. The left
      ventricular output, however, remained constant. The right ventricular output was
      382 +/- 106 mL/kg/min at control, and 391 +/- 117 mL/kg/min when paced at
      200/min, but decreased to 210 +/- 138 mL/kg/min when paced at 300/min, to 223 +/-
      102 mL/kg/min when paced at 350/min, and to 186 +/- 86 mL/kg/min when paced at
      400/min. Fetal circulatory failure occurred when the right atrium was paced at
      300/min or more.

PMID- 10087548
TI  - High impedance low energy pacing leads: long-term results with a very small
      surface area steroid-eluting lead compared to three conventional electrodes.
AB  - We evaluated the handling performance at implant, and the long-term atrial and
      ventricular electrical performance of a new generation using a very small surface
      area (1.2 mm2) steroid-eluting electrode (Medtronic CapSure Z). We compared the
      performance of CapSure Z to that of traditional passive fixation leads, with and
      without steroid elution. The study was conducted during 2 years of follow-up. We
      studied 188 patients (105 males and 83 females; mean age 71 +/- 7 years). All of
      the patients were implanted with a dual chamber pacemaker and the same type of
      lead in both chambers. Forty-one patients received CapSure Z leads, 25 patients
      received Target Tip leads (8-mm2 surface area; no steroid elution), 63 patients
      received CapSure leads (8-mm2 surface area; steroid elution), and 59 patients
      received CapSure SP leads (5.8-mm2 surface area; steroid elution). The four
      groups were homogeneous in regards to sex, age, cardiac disease, and reason for
      implant. At follow-up, the CapSure Z lead showed sensing values comparable to the
      other leads, with lower pacing thresholds and higher pacing impedance in both
      chambers. We evaluated the mean current drained from the pacemaker by the
      different types of leads when using safe, low energy output settings. We found
      that by using CapSure Z leads, the mean current was significantly lower than that
      of the other types of leads (0.42 microA for CapSure Z ventricular lead vs 0.85
      for CapSure SP, 1.42 for CapSure, and 1.54 for Target Tip). Thus, the use of the
      CapSure Z lead, combined with low energy output programming, will increase
      pacemaker longevity compared to the use of traditional leads and standard output
      programming.

PMID- 10087549
TI  - QT dispersion in children with ventricular arrhythmia and a structurally normal
      heart.
AB  - In adults, increased QT dispersion has been shown to predict arrhythmic risk as
      well as risk of sudden death in several clinical settings. It is not known
      whether or not QT dispersion is increased in children with idiopathic ventricular
      arrhythmia. We studied three groups of children: (1) 20 patients with idiopathic
      VT (aged 3-18 years; mean 11.2 years); (2) 30 patients with benign PVCs (aged 1
      20 years; mean 10.5 years); and (3) 30 control subjects (aged 4-17 years; mean 12
      years). Standard ECGs were reviewed and the dispersion of both QT and JT
      intervals was compared. No patient had structural heart disease or long QT
      syndrome. The QT and QTc dispersion (QT delta, QTc delta) among the three groups
      did not differ: QTc delta of the VT group was 70 ms +/- 30 ms, QTc delta of PVC
      patients was 60 ms +/- 30 ms, and the QTc delta of the control group was 65 ms +/
      30 ms. The JTc delta among the three groups did not differ as well: JTc delta of
      the VT group was 70 ms +/- 30 ms, the JTc delta of the PVC group was 60 msec +/-
      25 msec, and the JTc delta of the control group was 70 ms +/- 30 ms. We conclude
      that QT and JT dispersion are not significantly altered in children with
      idiopathic VT or benign PVCs when compared to control subjects. QT dispersion is
      not a reliable marker for arrhythmic risk in children with idiopathic ventricular
      arrhythmias and structurally normal hearts.

PMID- 10087550
TI  - Temperature response following nontraumatic low power radiofrequency application.
AB  - A marker for the efficiency of heating would be helpful in radiofrequency
      ablation of tachyarrhythmias. We hypothesized that changes of the catheter tip
      temperature during nontraumatic, very low power radiofrequency exposure would
      correlate with the temperature achieved during radiofrequency ablation, and
      therefore, could be used as a marker for heating efficiency. In 71 ablation
      attempts for drug refractory supraventricular tachycardias, the catheter tip
      temperature response to a 1-W-5-second test pulse was measured. Subsequently at
      the same site, radiofrequency current was delivered with a target temperature of
      70 degrees C and a power limit of 50 W. The test pulse, with a measured power
      level of 1.62 +/- 0.28 W, resulted in a heating efficiency of 0.78 +/- 0.60
      degree C/W. During ablation, the achieved tip temperature was 52.9 +/- 7.5
      degrees C, requiring a power output of 40.7 +/- 10.9 W. The heating efficiency
      was 0.57 +/- 0.74 degree C/W. The correlation between heating efficiency at low
      power and during radiofrequency ablation was linear with a correlation
      coefficient of 0.88. Regression analysis demonstrated that a heating efficiency
      above 1 degree C/W predicts a mean ablation temperature above 50 degrees C with
      more than 95% confidence interval. The temperature response to a very low power
      radiofrequency application correlates with the temperature rise achieved during
      radiofrequency ablation. It is suggested that delivery of low power
      radiofrequency current could be used to determine and monitor efficiency of
      heating during catheter mapping and ablation procedures.

PMID- 10087551
TI  - Atrial flutter: contemporary electrophysiology and catheter ablation.

PMID- 10087552
TI  - Focal radiofrequency catheter ablation of an irregularly irregular
      supraventricular tachycardia.

PMID- 10087553
TI  - Supporting high technology medicine through insurer-provider partnership.

PMID- 10087554
TI  - "Sagging heart syndrome": a cause of acute lead dislodgment in two patients.
AB  - Acute passive fixation atrial lead dislodgment occurred due to an unexpected and
      marked postural descent of the heart after permanent pacemaker implantation in
      two patients. Sagging of the heart in these two individuals may have been related
      to a history of morbid obesity followed by weight loss of over 100 pounds. Lead
      replacement with active fixation leads was required in both cases. The term
      "sagging heart syndrome" is proposed to describe this clinical entity. In certain
      adult populations, such as in patients with a history of significant weight loss,
      the "sagging heart syndrome" may represent a previously unrecognized cause of
      acute lead dislodgment.

PMID- 10087555
TI  - Sagging body parts.

PMID- 10087556
TI  - Supraventricular tachycardia terminated by external mechanical stimulation: a
      case of "pothole conversion".
AB  - Supraventricular tachycardia requires atrial or AV junctional tissue for its
      initiation and maintenance. Acute management of supraventricular tachycardias
      include vagal maneuvers, pharmacological treatment, and electrical cardioversion.
      We describe a case of a supraventricular tachycardias cardioverted by the jolt of
      the ambulance hitting a pothole. The proposed mechanism of cardioversion is an
      external mechanical one similar to the precordial thump.

PMID- 10087557
TI  - Impaired cardiac performance relating to delayed left atrial activation after
      atrial compartment operation for chronic atrial fibrillation.
AB  - In the presence of a normal atrial systole and optimal AV delay, atrial kick
      contributes to a significant fraction of the stroke volume. This atrial
      contribution may be lost during atrial asystole or mismatch in the timing of
      atrial and ventricular contraction. A patient received atrial compartment
      operation for his chronic AF. Although the AF was successfully converted to sinus
      rhythm, the conduction from the right to left atrium was markedly delayed so that
      the left atrial and ventricular activations occurred almost simultaneously. This
      delay in left atrial activation resulted in impaired cardiac performance.

PMID- 10087558
TI  - Catheter ablation in a patient with a congenital giant right atrial diverticulum
      presented as Wolff-Parkinson-White syndrome.
AB  - A young woman symptomatic for tachycardia showed right ventricular preexcitation
      on the surface ECG with a pattern during induced atrial fibrillation suggestive
      of multiple APs. Noninvasive imaging techniques performed prior to catheter
      ablation demonstrated the presence of a giant right atrial diverticulum confirmed
      by hemodynamic procedure. This structure functioned as an enormous accessory AP.
      We performed catheter ablation of this pathway using a special 4-mm multipolar
      catheter inside the diverticulum. This is the first case of such as anomaly being
      successfully treated with catheter ablation.

PMID- 10087559
TI  - Antidromic reciprocating tachycardia in patients with paraseptal accessory
      pathways: importance of critical delay in the reentry circuit.
AB  - Previous studies in patients with antidromic reciprocating tachycardia (ART) have
      observed a critical anatomic requirement (> 4 cm) between an antegrade bypass
      tract limb and a retrograde AV nodal limb. We report two patients with ART
      utilizing a paraseptal accessory pathway. In both cases, a critical degree of
      slow conduction within the circuit provides unusual electrophysiologic substrate
      to overcome the expected anatomical constraints.

PMID- 10087560
TI  - Atypical AV nodal reentry with bystander accessory pathway: an unusual mechanism
      of preexcited tachycardia.
AB  - We present an unusual mechanism of preexcited tachycardia--atypical AV nodal
      reentry with bystander AP. It can be differentiated from other preexcited
      tachycardias by its variable degree of preexcitation (either spontaneous or in
      response to atrial pacing), higher degree of preexcitation with pacing near the
      origin of the AP than during tachycardia, inability to preexcite the tachycardia
      by either late atrial or ventricular premature beats, the presence of
      nonpreexcited atypical AV nodal reentry tachycardia following successful AP
      ablation, and by exclusion of atrial tachycardia.

PMID- 10087561
TI  - Predominant tricuspid stenosis secondary to bacterial endocarditis in a patient
      with permanent pacemaker and balloon dilatation of the stenosis.
AB  - In a 49-year-old woman with sick sinus syndrome and a permanent VVI pacemaker,
      severe tricuspid stenosis and its clinical consequences developed 4 years after
      the attack of endocarditis. Besides the quite unusual occurrence of lead related
      tricuspid stenosis, successful treatment with balloon dilatation is the unique
      feature of this case.

PMID- 10087562
TI  - Torsade de pointes ventricular tachycardia during low dose intermittent
      dobutamine treatment in a patient with dilated cardiomyopathy and congestive
      heart failure.
AB  - The authors describe the case of a 56-year-old woman with chronic, severe heart
      failure secondary to dilated cardiomyopathy and absence of significant
      ventricular arrhythmias who developed QT prolongation and torsade de pointes
      ventricular tachycardia during one cycle of intermittent low dose (2.5 mcg/kg per
      min) dobutamine. This report of torsade de pointes ventricular tachycardia during
      intermittent dobutamine supports the hypothesis that unpredictable fatal
      arrhythmias may occur even with low doses and in patients with no history of
      significant rhythm disturbances. The mechanisms of proarrhythmic effects of
      Dubutamine are discussed.

PMID- 10087563
TI  - Disruption of pacemaker and defibrillator operation.

PMID- 10087564
TI  - Study of pacemaker and implantable cardioverter defibrillator triggering by
      electronic article surveillance devices.

PMID- 10087566
TI  - Safety alert on the ACCUFIX atrial "J" pacemaker.

PMID- 10087565
TI  - Four types of interaction between pacemakers and EAS systems.

PMID- 10087567
TI  - Internal phylogeny of the Chilopoda (Myriapoda, Arthropoda) using complete 18S
      rDNA and partial 28S rDNA sequences.
AB  - The internal phylogeny of the 'myriapod' class Chilopoda is evaluated for 12
      species belonging to the five extant centipede orders, using 18S rDNA complete
      gene sequence and 28S rDNA partial gene sequence data. Equally and differentially
      weighted parsimony, neighbour-joining and maximum-likelihood were used for
      phylogenetic reconstruction, and bootstrapping and branch support analyses were
      performed to evaluate tree topology stability. The results show that the
      Chilopoda constitute a monophyletic group that is divided into two lines,
      Notostigmophora (= Scutigeromorpha) and Pleurostigmophora, as found in previous
      morphological analyses. The Notostigmophora are markedly modified for their
      epigenic mode of life. The first offshoot of the Pleurostigmophora are the
      Lithobiomorpha, followed by the Craterostigmomorpha and by the Epimorpha s. str.
      (= Scolopendromorpha + Geophilomorpha), although strong support for the monophyly
      of the Epimorpha s. lat. (= Craterostigmomorpha + Epimorpha s. str.) is only
      found in the differentially weighted parsimony analysis.

PMID- 10087568
TI  - [Psychiatric Practice after a quarter of a century].

PMID- 10087569
TI  - ["Ideal" inpatient psychiatric treatment from the viewpoint of the patients].
AB  - PURPOSE: In this study "ideal" psychiatric inpatient care from the patient's
      point of view was examined. METHODS: Based upon a content analysis of 38
      interviews a questionnaire containing 39 items was developed to evaluate
      attributes of ideal psychiatric inpatient care from the patient's viewpoint. 58
      of 116 patients completed the questionnaire; the analysis group was
      representative for acute psychiatric inpatients. RESULTS: The patients ranked
      highly: successful treatment, upholding of human rights, privacy, empathic
      doctors, competent doctors, free exit, friendly staff. Factor analysis identified
      four factors that may be called Psychiatric Treatment, Patient Autonomy. Staff
      Competence, Appointment. The ratings were not associated with sociodemographic or
      disease-related variables. Therapists' ratings were mostly in agreement with
      those of the patients', but therapists underestimated the importance of the items
      free exit, patients' co-influence in treatment planning, respect among the
      patients. The aspect of patient autonomy was also rarely found in other
      professionals' questionnaires. CONCLUSIONS: Findings reflecting patients'
      expectations regarding "ideal" psychiatric inpatient care vary. Validity of
      former questionnaires is reduced if important aspects of patient satisfaction are
      disregarded.

PMID- 10087570
TI  - [Subjective quality of life of schizophrenic patients. Effect of treatment
      setting, psychopathology and extrapyramidal motor drug effects].
AB  - OBJECTIVE: In a cross-sectional study in 79 schizophrenic patients the quality of
      life (QOL) of a group of community-based patients under supervision of an
      outpatient unit (n = 47) and a group of long-stay patients in an inpatient
      rehabilitation centre in the same area (n = 32) was compared. METHODS: The
      patients' QOL was evaluated using the Lancashire Quality of Life Profile.
      Moreover psychopathology and extrapyramidal-motoric side-effects were assessed.
      RESULTS: Long-stay patients had a more distinct psychopathological symptomatology
      and more severe side-effects than community-based patients. After adjustment for
      psychopathology and side-effects, the subjective QOL of long-stay patients was
      significantly reduced in two out of eight life domains: housing and leisure
      activities. While psychopathology was negatively correlated with QOL, a subgroup
      with very marked psychopathology showed unexpectedly high QOL ratings.
      CONCLUSIONS: Results suggest that psychopathology is a stronger predictor of
      subjective QOL than side-effects and treatment setting. Patients with very
      distinct psychopathology probably use lower standards than others when evaluating
      their QOL which should be taken into consideration when analysing this type of
      data.

PMID- 10087571
TI  - [Acceptance of community psychiatry reform in the population. Results of a
      representative study in new German federal lands].
AB  - In 1993, a representative survey on the acceptance of community psychiatric
      services was conducted in the New German Lander. Its results show that the
      prospect of a hostel or group home for psychiatric patients to be established in
      their neighbourhood led to a predominantly negative reaction. On the other hand,
      the announcement that a day centre or a sheltered workshop should be opened was
      met with a more positive response. Only one quarter of those questioned supported
      the establishment of psychiatric units at general hospitals. Hence the acceptance
      of community psychiatric services in the east was clearly lower that in the
      western part of Germany. There was a clear association between the acceptance of
      community psychiatry and the general attitude towards the mentally ill. When
      respondents had personal experience with mental disorder, they were more open
      minded as regards the establishment of complementary psychiatric services.

PMID- 10087572
TI  - [Discharge in inpatient care. Results of a survey. Postscript to part III of the
      Berlin Deinstitutionalization Study].
AB  - PURPOSE: 42 percent long-term patients from the Berlin Deinstitutionalization
      Study sample have been discharged to full-time institutional settings. METHODS:
      The questionnaires of a mail-survey covered features of 58 different non-hospital
      full-time institutional settings and care for a group of 125 long-term mental
      patients. RESULTS: The return rate was more than 70 percent. For 78 percent of
      the discharged former long-term inpatients the political goal of complete
      psychiatric care in the patient's home area has been reached, but only 20 percent
      live in smaller institutions of up to 40 places. CONCLUSIONS: The significance of
      other data of the survey does not exceed that of stock-taking and certain
      indications because of the selective data and the limitations of the method.
      There is an urgent need for further research in examining the quality of non
      hospital institutional care for psychiatric long-term patients.

PMID- 10087573
TI  - [Admission status of alcohol and drug-dependent patients in "high threshold"
      access to withdrawal treatment].
AB  - OBJECTIVE AND METHODS: 106 patients (64.2% male and 35.8% female) who applied for
      a withdrawal treatment by phone call, were interviewed concerning the admission
      context with the aim to find out whether the admission regulations prevent
      patients from undergoing treatment. RESULTS: 72.6% of all patients were admitted
      as inpatients. The average waiting period was 8 days. 15.1% were known to have
      previously suffered from conclusions and 4.7% from delirium tremens; for these
      patients, the waiting period was significantly shorter. CONCLUSIONS: High
      threshold admission is not an insurmountable difficulty. Waiting periods and
      soberness at admission are accepted. Setting up admission conditions is, on the
      one hand, justified, whereas on the other hand chronic patients are often not
      reached. Telephone contacts with patients willing to undergo treatment should be
      replaced by contacts in an outpatient setting.

PMID- 10087574
TI  - [Organization of telephone counseling for psychosocial emergencies. An evaluation
      after 12 months].
AB  - OBJECTIVE: To improve the community-based health care in the area of Bonn a
      telephone consulting service and a mobile crisis intervention service have been
      established during a two year pilot project. The regional needs and structural
      demands have been assessed. RESULTS: During the first 12 months the number of
      calls increased from 15 in November 1996 to 76 in October 1997. In all, 432 calls
      were received. Most calls lasted from 10 to 30 minutes. 89% of the callers were
      female, 77% were in the age range between 30 and 45 years. Two-thirds of the
      callers had prior psychiatric treatments. Most callers suffered from loneliness
      and deficient coping strategies. CONCLUSION: The prove regional demands have led
      to a continuation of the project and an extension of the mobile crisis
      intervention service.

PMID- 10087575
TI  - [Suicide in the psychiatric clinic: weekend leave as risk factor. A qualitative
      analysis].
AB  - OBJECTIVE: The study focuses on biographic and social aspects including illness
      behaviour of psychiatric in-patients who committed suicide in weekend leave.
      METHOD: The authors undertake a retrospective qualitative analysis of 14 cases of
      inpatient suicide. RESULTS: 11 of 14 patients had been confronted during their
      weekend leaves with a milieu full of emotional conflicts with their spouses,
      parents or children. These conflicts had been of considerable subjective
      significance for the patients, who often experienced feelings of guilt and
      failure in their relations. CONCLUSION: Weekend leave of psychiatric inpatients
      is to be considered as a risk factor for suicide, a risk that must be taken into
      account before sending a patient home for the weekend.

PMID- 10087576
TI  - [The "Werther effect". Historical origin and background of a phenomenon].
AB  - OBJECTIVE: Ever so often one can read about the "Werther effect" in psychiatric
      literature. Until now this term has not lost its imaginative power, and still has
      its impact as well as being the subject of controversial discussion. METHOD: In
      order to clarify the "Werther effect", it seemed first of all necessary to
      illuminate the real biographical background of Goethe's "The sorrows of young
      Werther" and the extraordinarily eventful history of its reception. RESULTS: This
      essay also cites comments on this novel made by various personalities and
      authorities in an attempt to provide some hints on the real impact that Goethe's
      novel had at its time and showing the quarrels it brought about. CONCLUSIONS:
      Here the author comes to the conclusion that considering the ideologies
      prevailing at that time (late enlightenment and sentimentalism) the dispute about
      Goethe's work only aims at hiding the actual discussion about the people's right
      of self-determination.

PMID- 10087577
TI  - [A zoocentric Capgras syndrome].
AB  - Capgras syndrome is a delusional misidentification, a phenomenon where a person
      believes delusionally that another person (in most cases closely related) has
      been replaced by a double or impostor of identical appearance. It is usually a
      symptom of a functional psychosis but sometimes it is also associated with
      organic cerebral dysfunction. We present a case of a 23-year old women who had
      the delusional belief that her cat had been replaced by the cat of her former boy
      friend. Reviewing the literature we found that such a case is very rare. The
      association between Capgras syndrome and depersonalisation-derealisation
      phenomena is also pointed out.

PMID- 10087578
TI  - [Severe therapy refractory depression as initial manifestation of Parkinson
      disease].
AB  - A 60-year old female patient was referred to our University hospital with the
      diagnosis of severe treatment-resistant major depression to perform
      electroconvulsive therapy (ECT). For almost two years the patient had been
      treated with several antidepressants and, temporarily, neuroleptics. After
      showing no favourable response to ECT, the diagnosis of idiopathic Parkinson's
      disease was made and the patient was treated with L-dopa plus benserazide and
      pergolide in combination with the monoamine oxidase inhibitor moclobemide. Both
      depressed mood and motor symptoms showed dramatic improvement under this therapy.

PMID- 10087579
TI  - [Uncertain diabetes insipidus in a patient with affective psychosis].

PMID- 10087580
TI  - Bisphosphonates in clinical oncology. The development of pamidronate.

PMID- 10087585
TI  - [The economic evaluation of group examination for gastrointestinal disease in an
      electronics corporation--the cost-benefit analysis of follow-up study for peptic
      ulcer].
AB  - To investigate the usefulness of gastrointestinal fiberscope examination (GIF)
      for peptic ulcer in the health care station (station), a cost-benefit analysis
      was performed from the standpoint of the company, the health insurance society
      (insurance society), and workers. Before the analysis, the clinical course of the
      peptic ulcer, direct cost of the examination, and indirect cost due to time taken
      for the examination at the station were compared with those in a private hospital
      (hospital). In 1994, 202 cases of gastric ulcer (GU) (194 male cases, 8 female
      cases) and 199 cases of duodenal ulcer (DU) (195 male cases, 4 female cases)
      underwent GIF examination at the station. Cases of admission and emergency
      operation due to GU and DU at the station were less than those at the hospital.
      The benefits obtained for the company, the insurance society and the workers were
      as follows: we saw a decrease in the loss of working time, a decrease in the
      medical care cost, a decrease in patient cost sharing and a prevention of income
      loss due to admission (or prevention of the loss of a paid holiday). The time
      spent for GIF at the station was also less than at the hospital. This was a
      direct benefit for the company (a decrease in the loss of working time) and for
      the workers (prevention of the loss of a paid holiday). A further benefit for the
      company was a decrease in the cost of the miniature gastrointestinal mass survey
      of the workers who were followed up by GIF examination at the station. Total of
      more than 30 million yen in cost benefits was obtained. The economic evaluation
      of follow-up studies at the station was necessary to demonstrate the importance
      of health care to the company, and to the workers. A cost-benefit analysis was
      suited to this purpose, creating easily understandable results even if
      productivity did not count.

PMID- 10087586
TI  - [Generation of hydrogen peroxide during reduction of 2,4,6-trinitrotoluene and
      its related compounds].

PMID- 10087587
TI  - [Tobacco: ashes, smoke and carbon].
AB  - This review discusses the epidemiology, health effects and economic aspects of
      the tobacco epidemic. Smoking-related disorders have been known for decades and
      adverse effects of cigarette smoking are well documented. Nevertheless, tobacco
      use has increased dramatically in our century to become a global pandemic.
      Tobacco advertising attracts teenagers and encourages them to experiment with an
      addictive drug. To decrease uptake of smoking by adolescents, tobacco opponents
      propose advertising bans. They demand better protection for both active and
      passive smokers. These demands are in obvious contrast to the interests of the
      tobacco companies. Restriction of tobacco production and marketing could result
      in a substantial decrease in profits for tobacco manufacturers. Therefore, bills
      or regulations to control nicotine products are resisted by a strong tobacco
      lobby, especially in the USA. This article explains the marketing strategies of
      the tobacco industry and cost calculations of smoking. We describe preventive
      measures not only to stop adolescents taking up smoking but also to promote
      successful nicotine cessation.

PMID- 10087588
TI  - [Endovascular treatment of the abdominal aortic aneurysm: assessment,
      implantation technique, after-care and results].
AB  - BACKGROUND: Endovascular treatment of abdominal aortic aneurysm (AAA) is a new
      minimally invasive alternative to surgical repair. Patient selection,
      perioperative management, the procedure itself and postoperative follow-up are
      new aspects. PATIENTS: From June 1997 to June 1998, 37/70 patients (53%) with AAA
      were treated by the endovascular method. There were 35 males and two females,
      mean age 74 +/- 7 years, with a mean ASA class of 3.5 +/- 0.5. Graft repair was
      performed in 33 patients, due to inappropriate aortic anatomy for the
      endovascular technique in 24 and leaking aneurysm in 9. METHODS: Feasibility is
      based upon computed tomography and angiography. The procedure was performed in
      the operating room, under general, regional and local anaesthesia in 14, 3 and 20
      patients, respectively. 36 bifurcated and one tube endoprosthesis were implanted.
      An open access on one femoral or iliac artery and, in case of bifurcated
      prosthesis, usually a percutaneous access (10 Fr) on the other side were
      performed. Positioning and delivery were monitored under fluoroscopy. RESULTS:
      All the AAA could be sealed by the endovascular technique. In one patient, an
      iliac limb was removed surgically because of proximal misplacement, but the
      procedure was completed by the endovascular technique. Mean operation time was
      140 +/- 67 minutes. ICU stay was 1.4 +/- 1.6 days and patients were discharged
      after 6.5 +/- 3.5 days. Postoperative radiological follow-up showed totally
      sealed aneurysms in 34/37 patients (91%). In 3 patients a residual perfusion
      originating from a lumbar artery was observed. In 7/14 patients with AAA diameter
      > 6 cm and without residual leakage on the control CT scan, aneurysm pulsation
      remained after endovascular treatment. There was no early or late death after
      endovascular repair. During the follow-up period of 4 +/- 3 months patients are
      doing well. One patient needed balloon dilatation of an iliac limb. CONCLUSIONS:
      Endovascular treatment of AAA is a minimally invasive technique with short
      recovery time. This technique seems to be particularly advantageous in elderly or
      severely ill patients. Long-term controls are mandatory to identify potential
      complications, particularly when residual perfusion or aneurysm pulsation
      persists.

PMID- 10087589
TI  - [Pseudomonas pneumonia--an important differential pulmonary infiltration
      diagnosis in AIDS].
AB  - Bacterial pneumonias are the most common pulmonary complication in HIV-infected
      patients. Up to now, H. influenzae and S. pneumoniae have been described as the
      most important germs. Within a period of 4 years we diagnosed 15 cases of
      pneumonia caused by P. aeruginosa. All patients were in HIV stage C3; 3F, 12M;
      median age 34 (24-54) years; median CD4 count 10 (0-130) microliters. Except for
      3 nosocomial pneumonias, all others were community-acquired. Only 3 patients had
      neutropenia < 1000/microliter; 7 were intravenous drug abusers. Morphologically
      there were 6 cases of abscess pneumonia, in 3 of which pleural drainage was
      necessary because of pyopneumothorax. 4 patients showed bilateral infiltrates
      that could not be differentiated from those of P. carinii pneumonia. Our
      diagnosis was based on quantitative cultures of broncho-alveolar lavage fluid (9
      cases, two of them with concurrent positive blood cultures/positive cultures of
      the pleural fluid), pleural puncture (one case), sputum in pneumonias responding
      only to antipseudomonas therapy (3 cases), and autopsy (2 cases). 8 patients died
      of pseudomonas pneumonia within 1-3 months despite therapy. 7 patients received
      pseudomonas-specific combination therapy, but all died after median 9 (4-15)
      months of the underlying illness. In 3 cases recurrent pseudomonas pneumonia
      could be documented bacteriologically. We conclude that in HIV-infected patients
      pneumonia caused by P. aeruginosa is a significant and severe pulmonary
      complication.

PMID- 10087590
TI  - [Costs and benefits of heart failure treatment].
AB  - Congestive heart failure constitutes an important public health problem, because
      of its prevalence and mortality, and also its morbidity and significant resource
      utilization. It is the main cause of hospitalization for patients aged 65 or
      over, and it absorbs 2% of the health care budget in industrialized countries.
      With the aging of the population and the advancing age of the baby boom
      generation, the situation will worsen: the prevalence of congestive heart failure
      in Europe may increase by 70% by the year 2010. To favourably alter these
      economic consequences, treatment must not only prolong life but also slow down or
      even prevent disease progression towards more severe stages and decrease resource
      utilization, mainly in reducing the need for hospital admissions. To date, the
      most convincing results of economic analyses concern vasodilators: the
      hydralazine-isosorbide dinitrate combination and angiotensin converting enzyme
      inhibitors (ACE). Even if all these studies do not come to the same conclusions
      in terms of numbers, they agree in showing that costs per year of life saved by
      vasodilators, and particularly by ACE, are very favourable (< $10,000 per year of
      life saved) and much lower than those of most other well accepted medical
      strategies.

PMID- 10087591
TI  - [An unusual eye injury].

PMID- 10087592
TI  - [General trust and judgments of trustworthiness].
AB  - Contrary to the common sense idea that trustful people are gullible and easily
      believe whatever other people may say, past research reviewed by Rotter (1980a)
      indicated the idea was not necessarily valid. Two experiments of this paper
      further demonstrated that trustful people are more sensitive to information that
      indicates lack of trustworthiness in other people. In the experiments, subjects
      read a series of stories in which a person was about to make a choice between a
      trustworthy action and an untrustworthy one. Some of them were also given pieces
      of information regarding trustworthiness of the person. They were then asked to
      predict the likelihood of the person taking a trustworthy action. When no
      information was given, high trusters predicted with higher probability than low
      trusters that the person would take a trustworthy action. On the other hand, the
      high trusters lowered the predicted likelihood more steeply than the low when
      negative information was provided.

PMID- 10087593
TI  - [The role of local conjunction in the integration process of shape and color].
AB  - It is an open question how simple features are integrated in the attention
      spotlight. In this paper, we examined two opposing models for the integration
      process of shape and color. One is a local conjunction model in which simple
      features of shape and color are combined directly. The other is a whole
      conjunction model in which simple features of shape are integrated into the whole
      shape and then it is combined with color. In Experiment 1, we measured the time
      required to search for a target defined by a conjunction of shape and color for
      five subjects with changing coloring of the figures. The slope of the search
      function was gentler when corners of figures were colored (p < 0.01). In
      Experiment 2, we measured the time required to integrate shape and color of
      figures presented in rapid serial visual presentation (RSVP) for five subjects.
      The presentation time required to answer the correct combination was shorter when
      corners were colored (p < 0.01). These results support the local conjunction
      model.

PMID- 10087594
TI  - [Phonological priming and auditory event-related brain potentials].
AB  - Phonological priming effects on auditory event-related brain potentials were
      compared across different numbers of syllables shared between target words and
      preceding prime words or pseudowords. All items of words and pseudowords
      consisted of 3 syllables, and the subject's task was to make a judgment whether
      the item belonged to a designated category. A large negative wave (N400),
      commencing at about 250 ms poststimulus and lasting for about 700 ms, was
      observed irrespective of primes and targets. When targets were preceded by word
      primes that shared the first one or two syllables, the onset of N400 at the
      frontal site was earlier and the initial negative-going phase was steeper than in
      other conditions. In contrast, the magnitude of N400 to targets was reduced, when
      the primes were pseudowords that shared the first two syllables. These two types
      of early and later phonological priming effects were interpreted to reflect
      facilitations during spoken word recognition at the pre-lexical (phonological)
      and post-lexical (semantic or contextual integration) levels, respectively.

PMID- 10087595
TI  - [Effects of affective intensity and pleasantness on memory of dialogues].
AB  - This study was conducted to investigate the effects of affective intensity and
      pleasantness on memory. One hundred and nineteen undergraduates read 15
      dialogues, taking one speaker's position, and then rated each dialogue on two
      emotional dimensions. One hour later, subjects were given an incidental memory
      test about the dialogues. In agreement with most research done so far, recall for
      affectively intense dialogues was better than recall less intense dialogues. More
      importantly, it was indicated that recall for pleasant dialogues was better than
      that for unpleasant dialogues when the intensity level was high. It is necessary
      to consider not only affective intensity but also pleasantness when the relation
      between affective nature of stimuli and recall is discussed.

PMID- 10087596
TI  - [An investigation of age related slowing in cognitive processing speed in a
      mental rotation task].
AB  - The age related slowing in cognitive processing speed was investigated with a
      mental rotation task. Slope of regression line predicting reaction time from
      rotation angle was assumed to be an index of mental rotation speed, and the
      intercept increase when the task was changed standard to mirror image, an index
      of decision process speed. Three groups were compared: young control (mean age =
      19.1), younger elderly (M = 69.5) and older elderly (M = 79.0). In the mental
      rotation speed, an age difference between the control and older groups, but not
      between the older groups, was found. However, the decision process speed differed
      no only between the control and older groups, but also between the two older
      groups. These findings indicated that the effect of aging was larger on decision
      process than on mental rotation.

PMID- 10087598
TI  - [The effect of interviewer distance on eyeblinks and heart rates of interviewee].
AB  - The purpose of the present study was to investigate the effect of interviewer
      distance on interviewee eyeblinks and heart rates. The interviewer was a 22 year
      old woman, and 21 undergraduates, eight men and 13 women, participated in the
      study as interviewees. Interviews were conducted under three distance conditions:
      close (0.8 m), middle (2.0 m), and distant (4.0 m). A polygraph recorded the
      interviewee's eyeblinks and heart rates during the interview. After the
      interview, the interviewee rated his/her own psychological state during the
      interview, and reported impressions of the interviewer. Results showed that
      interviewees blinked more frequently in the close condition than the other
      conditions. No significant effect was found on heart rate. Interviewees rated
      their psychological state as more negative in the close condition, but impression
      to the interviewer remained the same across the conditions. These results
      indicated that eyeblink is a useful physiological index of effects that
      interpersonal situations have.

PMID- 10087599
TI  - [Self-reference effect on implicit and explicit memory tasks].
AB  - Judging whether words refer to oneself results in better memory than judging
      words on a semantic or physical basis. This phenomenon is known as self-reference
      effect. It is assumed that people encode more attribute when they are engaged in
      self-referent processing than when they are engaged in other types of processing,
      but it is not clear what kinds of attributes are encoded. In this study, the
      performance patterns of three judgment types (self, semantic, and physical) were
      measured in two conditions: A perceptual implicit memory test (the word-stem
      completion condition) and a conceptual explicit memory test (the word-stem cued
      recall condition). The results showed that in the explicit condition, both the
      self-reference effect and the levels-of-processing effect were obtained, but in
      the implicit condition, all judgments produced the same memory performance. This
      finding suggests that self-referent judgment produces a perceptual encoding that
      is similar to a perceptual encoding in semantic or physical judgment, and, that
      self-referent judgment produces more semantic and conceptual encoding than
      semantic or physical judgment.

PMID- 10087600
TI  - Xenoestrogens and phytoestrogens: bioremediation or biomonitoring?

PMID- 10087601
TI  - The maturation of nucleic acid technologies.

PMID- 10087603
TI  - The development of microfabricated biocatalytic fuel cells.
AB  - The production of electricity by biocatalytic fuel cells has been feasible for
      almost two decades and can produce electric power at a practical level. These
      fuel cells use immobilized microorganisms or enzymes as catalysts, and glucose as
      a fuel. A microfabricated enzyme battery has recently been made that is designed
      to function as a power supply for microsurgery robots or artificial organs.

PMID- 10087604
TI  - Detection of elementary flux modes in biochemical networks: a promising tool for
      pathway analysis and metabolic engineering.
AB  - Rational metabolic engineering requires powerful theoretical methods such as
      pathway analysis, in which the topology of metabolic networks is considered. All
      metabolic capabilities in steady states are composed of elementary flux modes,
      which are minimal sets of enzymes that can each generate valid steady states. The
      modes of the fructose-2,6-bisphosphate cycle, the combined tricarboxylic-acid
      glyoxylate-shunt system and tryptophan synthesis are used here for illustration.
      This approach can be used for many biotechnological applications such as
      increasing the yield of a product, channelling a product into desired pathways
      and in functional reconstruction from genomic data.

PMID- 10087605
TI  - Future prospects for artificial blood.
AB  - Concern about potential infective agents in donated blood has stimulated the
      recent development of blood substitutes. Chemically cross-linked hemoglobins are
      already undergoing clinical trials and might soon be ready for routine use. New
      generations of modified hemoglobin are being prepared to modulate the effects of
      nitric oxide and oxygen radicals, and artificial red blood cells are also under
      development.

PMID- 10087606
TI  - Enzymatic synthesis and modification of polymers in nonaqueous solvents.
AB  - Enzymes catalyse several reactions that are difficult to perform with chemical
      catalysts and that are important in the synthesis and modification of different
      polymers in organic solvents. In enzyme-based synthesis, alteration of the
      reaction medium can have a significant influence on the molecular weight,
      polydispersity, yield and architecture of the polymers that are produced.
      Modification of these macromolecules for industrial applications requires an
      understanding of the different reaction strategies involved.

PMID- 10087607
TI  - Comparative gene-expression analysis.
AB  - The study of differences in gene-expression patterns is one of the most promising
      approaches for understanding mechanisms of differentiation and development. In
      addition, the identification of disease-related target molecules opens new
      avenues for rational pharmaceutical intervention. Recent technical advances and
      improvements are accelerating the analysis of gene-expression profiles at the
      transcript level. The knowledge and comprehension of currently applied methods is
      one of the central criteria for an efficient and successful gene-screening
      approach.

PMID- 10087608
TI  - The in vivo delivery of heterologous proteins by microencapsulated recombinant
      cells.
AB  - The microencapsulation of recombinant cells is a novel and potentially cost
      effective method of heterologous protein delivery. A 'universal' cell line,
      genetically modified to secrete any desired protein, is immunologically protected
      from tissue rejection by enclosure in microcapsules. The microcapsule can then be
      implanted in different recipients to deliver recombinant proteins in vivo.

PMID- 10087609
TI  - Versatility in signalling: multiple responses to EGF receptor activation during
      Drosophila oogenesis.
AB  - The Drosophila epidermal growth factor receptor (EGFR) is active in different
      tissues and is involved in diverse processes such as patterning of the embryonic
      ectoderm, growth and differentiation of imaginal discs and cell survival. During
      oogenesis, the EGFR is expressed in the somatic follicle cells that surround
      individual oocyte-nurse cell complexes. In response to germline signals, the
      follicle cells differentiate in a complex pattern, which in turn leads to the
      establishment of the egg axes. Two recent reports have shown that the strategies
      used to pattern posterior follicle cells are different from those used to pattern
      dorsal follicle cells. In posterior follicle cells, EGFR activity is translated
      into an on-off response, whereas, in dorsal follicle cells, patterning mechanisms
      are initiated and refined by feedback that modulates receptor activity over time.

PMID- 10087610
TI  - Out of the ER--outfitters, escorts and guides.
AB  - The endoplasmic reticulum (ER) contains a variety of specialized proteins that
      interact with secretory proteins and facilitate their uptake into transport
      vesicles destined for the Golgi apparatus. These accessory proteins might induce
      and/or stabilize a conformation that is required for secretion competence or they
      might be directly involved in the sorting and uptake of secretory proteins into
      Golgi-bound vesicles. Recent efforts have aimed to identify and characterize the
      role of several of these substrate-specific accessory proteins.

PMID- 10087611
TI  - Putting E. coli on a pedestal: a unique system to study signal transduction and
      the actin cytoskeleton.
AB  - Enteropathogenic Escherichia coli (EPEC) subverts host signalling pathways and
      the cytoskeleton during infection, resulting in disease characterized by
      diarrhoea. Recent studies have revolutionized our understanding of the infection
      process by showing that this bacterium inserts its own receptor into the plasma
      membrane overlying the host actin cytoskeleton. The reorganized actin forms a
      pedestal-like structure with the bacterium at the tip. This review discusses the
      mechanism of infection and pedestal formation and how this system might be a
      powerful tool for studying actin dynamics at the plasma membrane.

PMID- 10087612
TI  - Waltzing with WASP.
AB  - Wiskott-Aldrich syndrome (WAS) is an inherited immune deficiency that is marked
      by eczema, bleeding and recurrent infections. The lymphocytes and platelets of
      WAS patients display cytoskeletal abnormalities, and their T lymphocytes show a
      diminished proliferative response to stimulation through the T-cell receptor-CD3
      complex (TCR-CD3). The product of the WAS gene, WAS protein (WASP), binds to the
      small GTPase Cdc42. Small GTPases of the Rho family are crucial for the
      regulation of the actin-based cytoskeleton. WASP and its relative NWASP might
      play an important role in regulating the actin cytoskeleton. Since both WASP and
      NWASP have the potential to bind to multiple proteins, they might serve as a hub
      to coordinate the redistribution of many cellular signals to the actin
      cytoskeleton. In this review, the authors discuss the possible role of WASP/NWASP
      and of the newly described protein WIP, which interacts with WASP and NWASP, in
      coupling signals from the T-cell receptor to the actin-based cytoskeleton.

PMID- 10087613
TI  - Responding to attraction: chemotaxis and chemotropism in Dictyostelium and yeast.
AB  - Polarized growth in response to external signals is essential for both the
      internal organization of cells and generation of complex multicellular structures
      during development. Oriented growth or movement requires specific detection of an
      external cue, reorganization of the cytoskeleton and subsequent growth or
      movement. Genetic approaches in both the budding yeast Saccharomyces cerevisiae
      and the social amoeba Dictyostelium discoideum have shed light on the molecular
      and cellular aspects of growth or movement towards an external signal. This
      review discusses the mechanisms and signalling pathways that enable yeast and
      Dictyostelium cells to translate external signals into directed growth and
      movement, respectively.

PMID- 10087614
TI  - Bi-cycling the furin pathway: from TGN localization to pathogen activation and
      embryogenesis.
AB  - Furin is a secretory pathway endoprotease that catalyses the maturation of a
      strikingly diverse group of proprotein substrates, ranging from growth factors
      and receptors to pathogen proteins, in multiple compartments within the trans
      Golgi network (TGN)/endosomal system. This review focuses on recent developments
      in the biochemistry and cell biology of the endoprotease, including the mechanism
      of TGN localization, phosphorylation-dependent regulation of protein traffic, and
      novel insights into early embryogenesis, extracellular matrix formation and
      pathogen virulence.

PMID- 10087615
TI  - 100 years of Golgi complexities.

PMID- 10087616
TI  - Soft x-ray microscopy.
AB  - Soft x-ray microscopes are beginning to provide information to complement that
      obtained from optical and electron microscopy. Soft x-ray microscopy can deliver
      30-nm resolution images of hydrated cells up to approximately 10 microns thick,
      and efforts towards obtaining higher resolution are under way. Although living
      specimens cannot be studied readily except in single exposures, fixed samples can
      be imaged at high resolution, and flash-frozen specimens can be studied without
      chemical modification and without significant radiation damage. Tomography is
      being developed for 3-D imaging, and spectromicroscopy offers unique capabilities
      for biochemical mapping of unlabelled structures beyond those of gold and
      fluorescent labels. Currently, most soft x-ray microscopes operate at synchrotron
      radiation facilities, but laboratory-scale microscopes are being developed too.

PMID- 10087617
TI  - Fluorescence lifetime imaging microscopy: spatial resolution of biochemical
      processes in the cell.
AB  - Fluorescence lifetime imaging microscopy (FLIM) is a technique in which the mean
      fluorescence lifetime of a chromophore is measured at each spatially resolvable
      element of a microscope image. The nanosecond excited-state lifetime is
      independent of probe concentration or light path length but dependent upon
      excited-state reactions such as fluorescence resonance energy transfer (FRET).
      These properties of fluorescence lifetimes allow exploration of the molecular
      environment of labelled macromolecules in the interior of cells. Imaging of
      fluorescence lifetimes enables biochemical reactions to be followed at each
      microscopically resolvable location within the cell.

PMID- 10087618
TI  - Dual-colour imaging with GFP variants.
AB  - Green fluorescent protein (GFP) has become an important tool in cell biology and
      is widely used as a reporter for imaging intracellular proteins and structures in
      live cells. Recently, spectral variants of GFP with red- and blue-shifted
      fluorescence emissions have been characterized, opening the possibility of double
      labelling with two different-coloured GFP fusion proteins. This article reviews
      recent advances in this technique, with special emphasis on time-lapse imaging
      applications in living cells.

PMID- 10087619
TI  - Using GFP in FRET-based applications.
AB  - The use of green fluorescent protein (GFP) is a powerful technology that has
      recently enabled investigators to study dynamic molecular events within living
      cells. One method for detecting molecular interactions involves fluorescence
      resonance energy transfer (FRET) between two GFPs or between GFP and a second
      fluorophore. This review summarizes the use of GFP for FRET and illustrates the
      theme with specific examples on how GFP has been employed as an intracellular
      molecular sensor.

PMID- 10087620
TI  - Photobleaching GFP reveals protein dynamics inside live cells.
AB  - Cell biologists have used photobleaching to investigate the lateral mobility of
      fluorophores on the cell surface since the 1970s. Fusions of green fluorescent
      protein (GFP) to specific proteins extend photobleaching techniques to the
      investigation of protein dynamics within the cell, leading to renewed interest in
      photobleaching experiments. This article revisits general photobleaching
      concepts, reviews what can be learned from them and discusses applications
      illustrating the potential of photobleaching GFP fusion proteins inside living
      cells.

PMID- 10087621
TI  - Imaging living cells and tissues by two-photon excitation microscopy.
AB  - Two-photon excitation microscopy provides attractive advantages over confocal
      microscopy for three-dimensionally resolved fluorescence imaging. Since two
      photon excitation occurs only at the focal point of the microscope, it inherently
      provides three-dimensional resolution. This localization of excitation also
      minimizes photobleaching and photodamage, which are the ultimate limiting factors
      in imaging living cells. Furthermore, no pinhole is required to attain three
      dimensional discrimination, so the efficiency of fluorescence collection is
      increased. These advantages allow experiments on thick living samples that would
      not be possible with other imaging techniques. The cost and complexity of the
      lasers required for two-photon excitation microscopy have limited its use, but
      appropriate turn-key lasers have now been introduced, and their cost should
      decrease. Finally, the recent introduction of commercial two-photon excitation
      laser-scanning microscope systems allows a much larger group of researchers
      access to this state-of-the-art methodology.

PMID- 10087622
TI  - Near-field scanning optical microscopy in cell biology.
AB  - Near-field optics has produced the highest optical resolution that has ever been
      achieved. The methods involved lie at the interface of far-field optical
      microscopy and scanned probe microscopy. This article describes the principles
      behind near-field scanning optical microscopy (NSOM) and highlights its potential
      in cell biology.

PMID- 10087623
TI  - Looking deeper into vertebrate development.
AB  - Magnetic resonance imaging (MRI) is a non-invasive imaging method that provides
      three-dimensional (3-D) images of the internal structure of opaque objects, such
      as humans and mice. In optimal situations, spatial resolution can approach the
      micron level. Arbitrarily oriented single-slice images can be obtained in
      seconds, with full 3-D volume images taking tens of minutes to collect. The
      exquisite sensitivity of MRI to the local physical and chemical environment
      provides a wide range of mechanisms giving rise to intrinsic contrast in the MR
      experiment, thus providing images with dramatic differences between different
      tissue types (e.g. white vs grey matter, myelinated vs unmyelinated fibres, and
      brain parenchyma vs ventricles). The recent advent of physiologically sensitive
      MRI contrast agents opens up a wealth of new avenues of study, even including the
      in vivo imaging of gene expression.

PMID- 10087624
TI  - Atomic force microscopy: a powerful tool to observe biomolecules at work.
AB  - Atomic force microscopes (AFMs) move a sharp tip attached to a soft cantilever in
      a TV-raster-like pattern over a surface and record deflections of the tip that
      correspond to the surface topography. When operated in physiological solutions,
      an AFM allows biomolecules to be observed in their native environment. Progress
      in instrumentation, sample-preparation methods and recording conditions has
      provided images of biomolecules and their assemblies that reveal submolecular
      details. In addition, the AFM allows conformational changes to be observed
      directly. This article discusses these points and illustrates them with some
      pertinent examples.

PMID- 10087625
TI  - Electron tomography of molecules and cells.

PMID- 10087626
TI  - A model for population growth of laboratory animals subjected to marker-assisted
      introgression: how many animals do we need?
AB  - This study provides methods for calculating the mean and variance of the number
      of animals with the desired genotype in each backcross generation for a marker
      assisted introgression experiment. The ultimate goal is to produce animals which
      are homozygous for the desired loci. The methods have been developed specifically
      for experiments with inbred lines. The model assumes a Poisson distribution for
      litter size, and is similar to that used in stochastic versions of population
      dynamics models. Certain biological parameters must be specified as well as
      parameters under the control of the breeder. These methods can be utilized in
      designing an experiment to determine the number of founder animals required,
      given the number of animals required at the completion of the backcross process
      and vice versa. Consideration is given to minimizing the total amount of
      genotyping over the entire experiment, by varying the number of times each
      backcrossed male is used. In addition, an outline is given for an adaptive design
      that allows for changes in male usage to be made during the experiment.

PMID- 10087627
TI  - Homoeologous chromosome pairing in the distant hybrid Alstroemeria aurea x A.
      inodora and the genome composition of its backcross derivatives determined by
      fluorescence in situ hybridization with species-specific probes.
AB  - A distant hybrid between two diploid species (2n = 2x = 16), Alstroemeria aurea
      and A. inodora, was investigated for homoeologous chromosome pairing,
      crossability with A. inodora and chromosome transmission to its BC1 offspring.
      Fluorescence in situ hybridization (FISH) with two species-specific probes, A001
      I (A. aurea specific) and D32-13 (A. inodora specific), was used to analyse
      chromosome pairing in the hybrid and the genome constitution of its BC1 progeny
      plants. High frequencies of associated chromosomes were observed in both
      genotypes of the F1 hybrid, A1P2-2 and A1P4. In the former, both univalents and
      bivalents were found at metaphase I, whereas the latter plant also showed tri-
      and quadrivalents. Based on the hybridization sites of DNA probes on the
      chromosomes of both parental species, it was established that hybrid A1P4
      contains a reciprocal translocation between the short arm of chromosome 1 and the
      long arm of chromosome 8 of A. inodora. Despite regular homoeologous chromosome
      pairing in 30% of the pollen mother cells, both hybrids were highly sterile. They
      were backcrossed reciprocally with one of the parental species, A. inodora. Two
      days after pollination, embryo rescue was applied and, eventually, six BC1
      progeny plants were obtained. Among these, two were aneuploids (2n = 2x + 1 = 17)
      and four were triploids (2n = 3x = 24). The aneuploid plants had originated when
      the interspecific hybrid was used as a female parent, indicating that n eggs were
      functional in the hybrid. In addition, 2n gametes were also functional in the
      hybrid, resulting in the four triploid BC1 plants. Of these four plants, three
      had received 2n pollen grains from the hybrid and one a 2n egg. Using FISH,
      homoeologous crossing over between the chromosomes of the two parental species in
      the hybrid was clearly detected in all BC1 plants. The relevance of these results
      for the process of introgression and the origin of n and 2n gametes are
      discussed.

PMID- 10087628
TI  - Wing-size heritability in a natural population of Drosophila subobscura.
AB  - Heritability of wing size was determined in a natural population of Drosophila
      subobscura for two consecutive year samples. In the 1988 sample, heritability in
      the laboratory environment was around 15%, whereas the lower bound in nature was
      around 0.1%. On the other hand, in the 1989 sample, heritability in the
      laboratory was around 90% and in nature around 15%. Differences between the two
      years could be caused by the more variable climate in which the males used as
      fathers of the 1988 sample developed. This indicates the importance of
      determining the environment in which parents developed in nature before
      discussing the heritability values obtained.

PMID- 10087629
TI  - [It is time tu bury those ancient trumpets in the basement].

PMID- 10087630
TI  - [Antibiotics, that only "disarm" the pathogen. Complex action mechanisms of
      modern antimicrobial substances].

PMID- 10087631
TI  - [Post-exposure prophylaxis. What to do when nosocomial infection by HBV, HCV or
      HIV is suspected?].

PMID- 10087632
TI  - [Action in cases of puncture injury by infected material].

PMID- 10087633
TI  - [Acute therapy of stroke].
AB  - Stroke is a neurological emergency that makes immediate hospitalization
      mandatory. Basic medical management includes maintenance of arterial blood
      pressure at an adequately high level, provision of an optimal supply of oxygen,
      and correction of hyperglycemia, hyperthermia and hypovolemia. Systemic
      thrombolytic therapy with rt-PA can be applied only within the first three hours
      after onset of symptoms and when hemorrhage has been excluded by a cranial CT
      scan. Heparin and aspirin have no proven therapeutic action, and are used only
      for early secondary prophylaxis.

PMID- 10087634
TI  - [Hemorrhage or ischemia, that is the question! Differential diagnostic signs for
      the practitioner].

PMID- 10087635
TI  - [From acute gastroenteritis to celiac disease. Pediatric gastroenterology].

PMID- 10087636
TI  - [Tumescent technique for local anesthesia. Use and prospectives of aa new
      anesthetic method].
AB  - The tumescent technique for local anesthesia (TLA) involves the infiltration of
      the subcutaneous fatty tissue with a large volume of a diluted local anesthetic.
      This large added volume increases the tension in the tissue, creating more
      favorable conditions for the action of the analgesic and for dermatological
      operative measures. Originally developed for use in the area of liposuction, TLA
      has since proved to have advantages over other forms of analgesia in numerous
      other dermatological indications. Overall, TLA is an effective and practical
      analgesic technique associated with comparatively few side effects that has been
      shown to be very useful in surgery of the skin.

PMID- 10087637
TI  - [The role of the family physician in the diagnosis of multiple sclerosis].

PMID- 10087638
TI  - [Building confidence through plain talk. How to talk about sexuality? Series:
      Medicine of Sexuality, 3: Free therapeutic talk].

PMID- 10087639
TI  - Intrusive memories in depression and posttraumatic stress disorder.
AB  - This study compared the stressors and consequent intrusive memories reported by
      matched samples of patients with posttraumatic stress disorder (PTSD) and major
      depression. Although intrusive memories were slightly more common among PTSD
      patients, both quantitative and qualitative measures revealed few differences
      between the groups. PTSD patients were more likely to have experienced personal
      illness or assault, and depressed patients family deaths and illness, and
      interpersonal events. Factor analysis of the associated emotions and memory
      characteristics suggested the existence of specific links between fear and
      reliving, and helplessness and out-of-body experiences. Possible inhibitory
      relationships between fear and sadness, and between guilt and anger, were also
      noted.

PMID- 10087640
TI  - Adolescent problem behavior: the influence of parents and peers.
AB  - This paper presents evidence that the Patterson et al. (1992) model of
      development of antisocial behavior in children generalizes to the development of
      a wide array of problem behaviors during later adolescence and that youth
      antisocial behavior, high-risk sexual behavior, academic failure and substance
      use form a single problem behavior construct. Structural equation modeling
      methods were applied to 24-month longitudinal data from 204 adolescents and
      parents. The model fit the data well, accounting for 52% of the variance in
      adolescent problem behavior. Specifically, families experiencing high levels of
      conflict were more likely to have low levels of parent-child involvement. These
      family conditions were related to poor parental monitoring and association with
      deviant peers one year later. Poor parental monitoring and associations with
      deviant peers were strong proximal predictors of engagement in an array of
      problem behaviors at two-year follow-up.

PMID- 10087641
TI  - Thought-action fusion as a causal factor in the development of intrusions.
AB  - Thought-action fusion refers to the tendency to treat thoughts and actions as
      equivalents. Some authors (e.g., Rachman, 1997; Behaviour Research and Therapy,
      35, 793-802) have suggested that thought-action fusion plays a role in the
      etiology of obsessive intrusions. The present study sought to test this idea.
      Subjects (n = 19) in the experimental condition underwent a bogus EEG recording
      session. They were informed that the apparatus was able to pick up the word
      'apple' and that thoughts of that word could result in the administration of
      electrical shocks to another person. After having spent 15 minutes in the EEG
      laboratory, experimental subjects and controls (n = 26) completed a short
      questionnaire containing items about characteristics of the target thought (e.g.,
      frequency, aversiveness). Results indicate that thought-action fusion, indeed,
      promotes intrusive thinking in that it results in a higher frequency of target
      thoughts, more discomfort, and more resistance. Thus, the current findings
      support the idea that thought-action fusion may contribute to the development of
      obsessive intrusions.

PMID- 10087642
TI  - Responsibility and perfectionism in OCD: an experimental study.
AB  - Cognitive models of obsessive-compulsive disorder (OCD) suggest a number of
      different variables that may play a role in the development and maintenance of
      obsessive compulsive symptoms [Freeston, M. H., Rheaume, J., & Ladouceur, R.
      (1996) Correcting faulty appraisals of obsessional thoughts. Behaviour Research
      and Therapy, 34, 433-446]. This study's aim was to verify the effect of
      perfectionism and excessive responsibility on checking behaviors and related
      variables. Twenty-four moderately perfectionistic subjects (MP) and 27 highly
      perfectionistic subjects (HP) were submitted to a manipulation of responsibility
      (low and high). After each manipulation, they had to perform a classification
      task during which checking behaviors were observed. Results indicate that more
      checking behaviors (hesitations, checking) occurred in the high responsibility
      condition than in the low responsibility condition for subjects of both groups.
      After executing the task in the high responsibility condition, HP subjects
      reported more influence over and responsibility for negative consequences than MP
      subjects. These results suggest that high perfectionistic tendencies could
      predispose individuals to overestimate their perceived responsibility for
      negative events. Furthermore, perfectionism could be conceived as playing a
      catalytic role in the perception of responsibility. Results are discussed
      according to cognitive models of OCD.

PMID- 10087643
TI  - Exposure to disgust-evoking imagery and information processing biases in blood
      injection-injury phobia.
AB  - Biased processing of threat-relevant information is a central construct among
      contemporary theories of anxiety. However, biases in attentional and memory
      processes have not been systematically investigated in blood-injection-injury
      (BII) phobia. Theory has suggested that disgust rather than fear characterizes
      BII phobia and may mediate processing biases differently. We investigated the
      effects of a disgust mood induction on attention and memory in BII phobic and
      nonphobic participants. The Stroop task failed to demonstrate an attentional bias
      toward medical and disgust words, even under conditions of disgust provocation.
      However, an implicit memory task showed that BII phobics completed more medical
      and disgust word stems than nonphobics. These results suggest that BII phobia may
      be characterized by a similar implicit memory, but not an attentional, bias found
      in other anxiety disorders. As such, information processing in BII phobia may be
      qualitatively different from other anxiety disorders. Implications for further
      research regarding information processing biases in BII phobia are discussed.

PMID- 10087644
TI  - The psychosocial effects of rheumatoid arthritis on the patient and the well
      partner.
AB  - Rheumatoid arthritis (RA) is a chronic disorder that can have a severe impact on
      patient's lives. This present study investigated four questions regarding the
      psychosocial effects on patients and their well partners. First we found that
      depression for both patients and partners were slightly elevated and 35.7% of
      patients and 23.3% of well partners had scores above the cut-off for possible
      clinical depression on the Center for Epidemiological Studies Depression Scale.
      Second, there was no significant difference between the patients' level of
      distress and that of the partners. Third, there were moderate positive
      correlations between patients' and partners' scores on measure of psychological
      functioning. Fourth, there were no differences in either the patients' or
      partners' well-being based on the gender of the patient. Finally, an exploratory
      analysis was conducted to examine the factors which influence the patients' and
      partners' depression and their view of the relationship.

PMID- 10087645
TI  - Disgust sensitivity and the sex difference in fears to common indigenous animals.
AB  - Davey's mediational hypothesis [Davey, G. C. L. (1994). Self-reported fears to
      common indigenous animals in an adult UK population: the role of disgust
      sensitivity. British Journal of Psychology, 85, 541-554.] suggests that the sex
      difference in self-assessed animal fears can be accounted for by the sex
      difference in disgust sensitivity. An empirical test failed to support this
      hypothesis in a non-clinical sample (N = 214). Holding constant the influences of
      confounders such as age, fear of contamination, sex roles, neuroticism,
      psychoticism and disgust sensitivity, biological sex kept emerging as a
      significant predictor in relation to four types of animal fears (fear-relevant
      animals, dry or non-slimy invertebrates, slimy or wet looking animals and farm
      animals). Other things being equal, high disgust sensitivity either lost its
      predictive capability (in relation to dry or non-slimy invertebrates and slimy or
      wet looking animals) or predicted high fear of fear-relevant animals and of farm
      animals inequivalently across, respectively, the sexes (high in females only) and
      age groups (high in the old only). A multifactorial, interactionist approach
      should be advocated in the study of the aetiology of animal fears if progress in
      this area is to be achieved.

PMID- 10087646
TI  - Schizophrenia: refining the phenotype, resolving endophenotypes.
AB  - The conceptual history of the diagnosis of schizophrenia is reviewed and the
      current definition of the illness is examined (e.g. DSM-IV). A dimensional
      alternative to the traditional categorical model of diagnosis is discussed with a
      specific emphasis on the four dimensions of psychopathology represented by
      reality distortion (hallucinations, delusions), disorganization (positive formal
      thought disorder, bizarre behavior), negative symptoms (flattened affect,
      avolition, alogia, asociality), and premorbid social functioning. Also discussed
      is the development of structured psychiatric interviews that emerged from the
      clinical/research context that gave rise to explicit (i.e. operational)
      diagnostic criteria for schizophrenia. The general methodological approach used
      to detect valid endophenotypes for schizophrenia liability--i.e. indicators of
      liability not visible to the unaided naked eye--as well as their potential
      diagnostic and research utility is presented in overview. The rationale for
      linking such indicators to schizophrenia liability, which is conceptualized as a
      latent construct, is also reviewed. Future directions in the development and
      refinement of the diagnostic approach to schizophrenia and schizophrenia
      liability are highlighted.

PMID- 10087647
TI  - The stability and reversibility of Th1 and Th2 populations.

PMID- 10087648
TI  - T helper differentiation proceeds through Stat1-dependent, Stat4-dependent and
      Stat4-independent phases.
AB  - Much of our focus in understanding Th1/Th2 development has been on the signals
      delivered by IL-12 and IL-4 as final determinants of terminal T cell
      differentiation. Because extinction of IL-12 signaling in early Th2 development
      could potentially be important in imprinting a more permanent Th2 phenotype on a
      population of T cells, we have also examined various parameters regulating the IL
      12 signaling pathway. Whereas IL-4 appears to repress functional IL-12 signaling
      through inhibition of IL-12R beta 2 expression, IFN-gamma in the mouse, and IFN
      alpha in the human appear to induce IL-12R beta 2 expression and promote IL-12
      responsiveness. We propose that Th1 development can be considered in two stages,
      capacitance and development. Capacitance would simply involve expression of IL
      12R beta 1 and beta 2 subunits, regulated by TCR, IL-4 and IFNs. The second
      stage, development, we propose is the true IL-12 induced developmental stage,
      involving expression of Stat4 inducible proteins. In the human, this may also
      occur via IFN-alpha, which is able to activate Stat4. It is perhaps possible that
      all of Stat4 actions on Th1 development may be exert directly by Stat4 at the IFN
      gamma gene, however we suggest that, more likely, Stat4 may act to induce Th1
      development through the induction of other non-cytokine genes, whose stable
      expression maintains the transcriptional state of a Th1 cell.

PMID- 10087649
TI  - Redirecting Th2 responses in allergy.

PMID- 10087650
TI  - Interleukin-12: basic principles and clinical applications.

PMID- 10087651
TI  - Redirecting Th1 and Th2 responses in autoimmune disease.

PMID- 10087652
TI  - Manipulation of Th responses by oral tolerance.

PMID- 10087653
TI  - The discovery of Campylobacter-like organisms.

PMID- 10087654
TI  - The epidemiology of Helicobacter pylori.

PMID- 10087655
TI  - Chronic gastritis and nonulcer dyspepsia.

PMID- 10087656
TI  - The role of Helicobacter pylori infection in duodenal and gastric ulcer.

PMID- 10087657
TI  - Gastric cancer and lymphoma.

PMID- 10087658
TI  - Pediatric Helicobacter pylori infection: clinical manifestations, diagnosis, and
      therapy.

PMID- 10087659
TI  - Microbiology of Helicobacter pylori.

PMID- 10087660
TI  - Animal models of Helicobacter gastritis.

PMID- 10087661
TI  - Mechanisms of Helicobacter pylori infection: bacterial factors.
AB  - Since the discovery of H. pylori in 1982 (MARSHALL 1983; WARREN 1983), research
      on the mechanisms of virulence of H. pylori has advanced substantially. It is now
      well established that urease and flagella are virulence factors of H. pylori.
      Although known for some time to be toxic to epithelial cells in vitro, VacA has
      only recently been established as a virulence factor. The cag pathogenicity
      island has also emerged as another virulence contender, although the specific
      genes involved in virulence are still being determined. Other possible virulence
      factors, not yet confirmed by gene disruptions, are hapA, katA, sodA, cagA, and
      iron-regulated genes. As of yet, no adhesins have been confirmed as being
      important for in vivo survival of H. pylori. With the sequence of the H. pylori
      genome in hand, it should be possible to more easily determine the role of
      specific genes in virulence. Genes of immediate interest are the OMPs, which may
      under go phase and antigenic variation and may represent adhesins. Additionally,
      virulence-related orthologs and vacA-related genes may provide some interesting
      findings. Once we define the genes that contribute to H. pylori virulence, we may
      be able to more easily develop novel therapeutic drugs or vaccines to treat and
      prevent H. pylori infection.

PMID- 10087662
TI  - Host response and vaccine development to Helicobacter pylori infection.
AB  - Studies in both humans and animals demonstrate that H. pylori is capable of
      illiciting an innate response that in part is regulated by the genetic makeup of
      the host. These innate responses includes stimulating immune effector mechanisms
      at the cellular and biochemical level resulting in the influx of neutrophils into
      the lamina propria and have even been shown to modify gastric acid secretion. The
      availability of good animal models of chronic Helicobacter infection has also
      allowed investigators to begin to examine how the adaptive host immune response
      prevents and/or exacerbates Helicobacter-induced gastroduodenal disease. The
      experimental H. felis/mouse model has been utilized by a number of laboratories
      to investigate mechanisms of host defense against chronic Helicobacter infection.
      This model and the more recently developed H. pylori rodent model has not only
      allowed investigators to confirm the feasibility of immunotherapy to prevent
      and/or cure Helicobacter infection but also to begin to examine how the host
      immune response prevents and/or exacerbates Helicobacter-induced gastroduodenal
      disease. Based on these studies a hypothesis is emerging that suggests that
      protection and/or cure from Helicobacter infection is mediated primarily by an
      upregulated cellular immune response which may act via an antibody independent
      mechanism. Paradoxically, following natural infection with H. pylori, a component
      of the cellular immune response also promotes chronic gastric inflammation
      without clearance of the organism. The recent development of reliable and
      reproducible H. pylori/rodent models of disease and the availability of numerous
      inbred strains, transgenic and knockout animals, will allow investigators to
      continue to explore the role the host cellular and humoral immune response plays
      in promoting or preventing this infection.

PMID- 10087663
TI  - Diagnosis of Helicobacter pylori infection.

PMID- 10087664
TI  - Economic perspectives in the management of Helicobacter pylori infections.

PMID- 10087665
TI  - Antibiotic treatment of Helicobacter pylori infection.

PMID- 10087666
TI  - Helicobacter pylori and the future: an afterword.

PMID- 10087667
TI  - [Pathophysiology and therapy of patients with Budd-Chiari syndrome].

PMID- 10087669
TI  - Impaired oxygen utilization during rapid cooling on cardiopulmonary bypass.
AB  - Little attention has been paid to oxygen demand/supply balance during the cooling
      phase of cardiopulmonary bypass (CPB). We examined the changes in systemic oxygen
      utilization caused by the initiation of deep hypothermic CPB. METHODS: We
      calculated the changes in systemic oxygen consumption (VO2) and its related
      parameters in 5 patients who underwent reconstruction of the aortic arch using
      deep hypothermic CPB. Rectal temperature was decreased to 18 centigrade on
      average. RESULTS: VO2 decreased immediately after the initiation of hypothermic
      CPB. VO2 decreased by an average of 50% and 64%, while rectal temperatures
      decreased from 35 to 34 and 32 centigrade, respectively. Hemoglobin-bound oxygen
      accounted for 68% of VO2 just before CPB and 28% after the rectal temperature
      decreased to 32 centigrade. This decrease in VO2 correlated with the maximum
      temperature gradient between the venous and the arterial blood during the cooling
      phase. The abrupt decrease in VO2 by initiating CPB was associated with an
      increase in mixed venous oxygen saturation and a decrease in oxygen extraction
      ratio. VO2 values during the cooling phase were much lower than those during the
      rewarming phase at any given rectal temperatures. VO2 values at rectal
      temperatures of 34 and 32 centigrade during the cooling phase of CPB were 40% and
      29% of those during the rewarming phase of CPB, respectively. This difference was
      caused by the changes in VO2 derived from hemoglobin-bound oxygen, and VO2
      derived from dissolved oxygen did not show any significant changes during the
      cooling and the rewarming phase. Hysteresis of VO2 was also observed as a
      function of the nasopharyngeal temperature. The arterial lactate concentration
      showed an insignificant but gradual increase during the cooling phase.
      CONCLUSION: These observations suggested that an immediate decrease in VO2 and
      the following low values of VO2 caused by the initiation of deep hypothermic CPB
      could not be simply due to a decrease in the metabolic rate for oxygen but rather
      due to disturbances in oxygen utilization, one of which seemed to be caused by
      the impaired oxygen release from hemoglobin. It was also suggested that an
      increase in mixed venous oxygen saturation by initiating hypothermic CPB did not
      necessarily indicate an adequate oxygen/demand supply balance.

PMID- 10087668
TI  - The expression of proliferating cell nuclear antigen (PCNA) and p 53 protein
      correlate with prognosis of patients with oral squamous cell carcinoma.
AB  - Few Data are available regarding expression of proliferating cell nuclear antigen
      (PCNA) versus overexpression of p 53 protein and prognosis for oral squamous cell
      carcinoma (O-SCC). This study evaluated the relationship between expression of
      PCNA and p 53 protein and certain clinical and pathologic parameters to prognosis
      in O-SCC. Scattered PCNA immunoreactive cells were found in 50 of 51 (98.0%)
      tumors. The mean PCNA-labelling index (PCNA-LI) of O-SCC was 34.7 +/- 12.0% (n =
      50). The PCNA-LI was significantly high in O-SCC when compared to normal squamous
      epithelium (3.9 +/- 2.1%, n = 10). Altogether, 28 of 51 (54.9%) tumors showed
      nuclear immunoreactive for the p 53 protein. p 53-positive nuclei were clearly
      stained as granular or reticular in O-SCC. Microscopically, it appeared that the
      staining patterns of PCNA- and p 53-positive cells were quite similar. The mean
      value of PCNA-LI for the p 53-positive cases was 37.9 +/- 11.9% (n = 28), which
      was significantly higher than the 30.8 +/- 11.1% of the 23 negative cases. The
      survival rates at 3-year and 5-year for patients with p 53-negative O-SCC were
      78.3% and 73.4%, respectively, while those for patients with p 53-positive O-SCC
      were 51.9% and 43.2%, respectively. No significant correlation could be found
      between PCNA-LI and T classification, N classification and Stage classification.
      The expression of p 53 was detected in 48.5% (16/33) of cases without regional
      lymph node metastasis, and 66.7% (12/18) with regional lymph node metastasis.
      There was a significant difference between PCNA-LI and p 53-positive cases, and
      prognosis. In PCNA-LI, the Grade 4 by mode of invasion was significantly higher
      than Grade 1, 2 and 3. The PCNA-LI and p 53-positive cases were significantly
      correlated with histological grading of malignancy. The present study shows a
      relationship between PCNA and p 53 protein. It also suggests that both PCNA and p
      53 positive rates are the malignant potential of the O-SCC.

PMID- 10087670
TI  - On time savers.

PMID- 10087671
TI  - Videotapes in evaluating work-related upper extremity symptoms.
AB  - Thirteen patients with upper extremity symptoms that were claimed to have
      occurred in the course of employment were evaluated to determine the role of
      videotapes in their evaluation and management. Videotapes were of two types: work
      demonstration by patient or coworker (8 tapes) and surveillance tapes obtained by
      a private investigator (5 tapes). Four of eight work station videotapes
      demonstrated significant repetitive motion that could have contributed to their
      symptoms. Four of eight work station videotapes demonstrated that the tasks were
      neither forceful nor repetitive in nature. Return to work recommendations were
      made based on both clinical grounds and job site information provided on tape.
      After viewing five surveillance videotapes, two fraudulent claims were settled
      soon after medical opinions were rendered. Two patients were declared able to
      return to work; one returned to work and the other was dismissed. The videotape
      of patient No. 13 was not crucial for the decision and he was authorized to have
      surgery. The opinions formed concerning the causality of alleged claims of injury
      were often altered by viewing the content of the videotapes. Videotapes are a
      valuable tool and useful adjunct in the overall management of the workers with
      upper extremity symptoms.

PMID- 10087672
TI  - Leptospirosis.

PMID- 10087673
TI  - A practical approach to managing community dwellers with Alzheimer's disease.
AB  - This article will review multiple strategies and treatment options that can be
      utilized by clinicians to address the ever-changing and varied needs of community
      dwelling elders with Alzheimer's disease and those of their families.
      Comprehensive assessment and the judicious use of medications, together with
      other nonpharmacological interventions, may lessen the burden of care on families
      and decrease the likelihood of institutionalization.

PMID- 10087674
TI  - Juvenile delinquency in American Indian youths: historical and cultural factors.
AB  - This paper addresses health aspects of juvenile delinquency in American Indian
      youths. Comorbid conditions such as substance abuse and depression often
      complicate diagnosis and treatment. A survey of the literature and an examination
      of cultural, family, and school issues that influence the presentation and
      management of conduct problems in Native American youths are included. Cases are
      presented to emphasize the importance of cultural sensitivity in clinical
      assessment and intervention.

PMID- 10087675
TI  - Squamous cell carcinoma of the breast following silicone injection of the
      breasts.
AB  - During the 1960s, injecting liquid silicone into the breasts for augmentation
      purposes was a common practice. Many women suffered complications, usually
      developing silicone mastopathy, but there have been reports of carcinoma as well.
      A case of squamous cell carcinoma of the breast is reported in a patient who had
      previously undergone injection of silicone into the breasts. Upon review of the
      literature, this is only the second reported case of squamous cell carcinoma of
      the breast following silicone injection. Squamous cell carcinoma of the breast is
      a very rare tumor comprising 0.04 to 0.075 percent of all breast malignancies.
      The tumor appears to develop from metaplasia of benign epithelial cells within
      the breast. Many theories are presented for the development of this metaplastic
      process. The clinical presentation, evaluation, and treatment of squamous cell
      carcinoma of the breast is quite similar to that of infiltrating ductal carcinoma
      of the breast of comparable stage and size.

PMID- 10087676
TI  - Reflections of thrombosis research in Oklahoma City--1975 to the present.

PMID- 10087677
TI  - Diphtheria vaccine recalled by FDA.

PMID- 10087678
TI  - Anorexia, OCD, and streptococcus.

PMID- 10087679
TI  - PDD-NOS.

PMID- 10087680
TI  - Risperdal and parkinsonian tremor.

PMID- 10087681
TI  - Citalopram and fluvoxamine in Tourette's disorder.

PMID- 10087682
TI  - Violence and related psychopathology.

PMID- 10087683
TI  - Violent behavior in children and youth: preventive intervention from a
      psychiatric perspective. Group for the Advancement of Psychiatry, Committee on
      Preventive Psychiatry.
AB  - OBJECTIVE: To outline causative factors for the epidemic of violence among
      children and youth in North America and suggest roles for child and adolescent
      psychiatry in preventive intervention. METHOD: The committee used literature
      searches to identify biological, psychological, and sociocultural factors
      associated with violent behavior. RESULTS: Children and youth are both victims
      and perpetrators of violence. Risk factors include socioeconomic status,
      difficult temperament, chronic illness, psychiatric comorbidity, and parental
      psychopathology. Access to firearms in a culture of violence presents a
      particularly serious risk. Protective factors include intact family structures,
      prosocial peer groups, and supportive communities. Preventive interventions
      include the following: universal, addressed to total population groups;
      selective, for at-risk populations; and indicated, for children and youth
      developing violent behavior. Universal interventions including gun control and
      improved perinatal care are helpful, and selective interventions such as gun-free
      zones around schools may be successful. Indicated programs such as gun
      confiscation and conflict resolution for youth at serious risk may be useful, but
      only when embedded within well-funded, clinically based, and community-focused
      programs. Single-emphasis programs such as "Boot Camps" have intuitive appeal,
      but their utility is doubtful. CONCLUSIONS: Violent behavior can be prevented,
      and child and adolescent psychiatrists must be more active in community
      preventive interventions.

PMID- 10087684
TI  - Multisystemic treatment of criminality and violence in adolescents.
AB  - OBJECTIVE: To discuss the emergent success of multisystemic therapy (MST), a
      family-based therapeutic approach that has been viewed as a promising treatment
      for violence and other serious antisocial behaviors in adolescents. METHOD: The
      empirical underpinnings, theoretical foundation, and clinical features of MST are
      described, followed by a brief review of studies of MST effectiveness with
      serious juvenile offenders. RESULTS: The theoretical foundation and clinical
      features of MST draw upon empirical findings regarding the multidetermined nature
      of serious antisocial behavior as well as upon social-ecological models of
      behavior in which the youth and family's school, work, peers, and neighborhood
      are viewed as interconnected systems with dynamic and reciprocal influences on
      the behavior of family members. In controlled studies with serious juvenile
      offenders, MST has demonstrated long-term reductions in criminal activity,
      violent offenses, drug-related arrests, and incarceration. CONCLUSIONS: The
      success of MST can be attributed primarily to (1) the match between MST
      intervention foci and empirically identified correlates/causes of criminality and
      violence in adolescents (e.g., parental discipline, family affective relations,
      peer associations, school performance) and (2) the flexible use of well-validated
      intervention strategies in the natural environment.

PMID- 10087685
TI  - Suicide and violence prevention: parent education in the emergency department.
AB  - OBJECTIVE: To determine prospectively whether parental receipt of injury
      prevention education is associated with new action limiting access to lethal
      means and if so, what action was taken for which means. METHOD: Prospective
      follow-up of 103 adults whose children made an emergency department visit for
      mental health assessment or treatment. Record review assessed whether hospital
      staff provided injury prevention education. Logistic regression was used to
      determine the likelihood of new caretaker action limiting access to the following
      potentially lethal means: firearms, alcohol, prescription medications, and over
      the-counter medications. RESULTS: Significant associations were found between
      exposure to injury prevention education and action to limit access (adjusted odds
      ratio = 3.6, 95% confidence interval = 1.1-12.1, p = .04). Five of 8 adults whose
      households contained firearms took new action to limit access after injury
      prevention education, whereas none of the 7 firearm-owning families who did not
      receive injury prevention education took new action to limit firearm access.
      Similar patterns were seen for other means. Adults more often chose to lock up
      rather than dispose of lethal means. CONCLUSIONS: Injury prevention education
      should be provided to parents during child/adolescent emergency department mental
      health-related visits. Potential for violence prevention is real because parents
      do take new action to limit access to lethal means when means restriction
      education is provided.

PMID- 10087686
TI  - Personality traits in juvenile delinquents: relation to criminal behavior and
      recidivism.
AB  - OBJECTIVE: To examine the relation between personality traits and criminal
      behavior and to determine whether such factors are predictive of future
      recidivism. METHOD: A sample of 481 incarcerated males (mean age = 16 years)
      completed questionnaires assessing distress and restraint relating to personality
      characteristics. In addition, official criminological data were gathered from
      subjects' records. A subsample of 148 juveniles was followed up to 4.5 years
      after release and examined for rearrests and time out of prison since last
      incarceration. RESULTS: Results indicate a significant association between self
      reported levels of distress and restraint and prior criminal behavior as well as
      behavior during incarceration. Furthermore, of the sample surveyed, 67% were
      rearrested. Personality traits measured during incarceration were predictive of
      recidivism rates, above and beyond the effects of such criminological factors as
      age and number of prior offenses. CONCLUSIONS: The results support the view that
      juvenile delinquents are a heterogeneous population in terms of personality
      features. These traits have discriminant and predictive validity. Adding
      personality measures to the assessment of delinquents may further our
      understanding of how personality influences criminal activity and future
      recidivism. We may be able to use this understanding to target specific domains
      of functioning to develop more effective intervention strategies.

PMID- 10087687
TI  - A clinical trial for adolescent depression: predictors of additional treatment in
      the acute and follow-up phases of the trial.
AB  - OBJECTIVE: To examine the predictors of additional service use among participants
      in a clinical trial for depression. METHOD: 107 adolescents with DSM-III-R
      depression were randomly assigned to receive either cognitive-behavioral therapy,
      systemic behavioral family therapy, or nondirective supportive therapy for 12 to
      16 weeks of acute treatment and followed up periodically for 24 months after the
      termination of acute treatment. RESULTS: More than half (53.3%) of the 107
      randomized adolescents received additional treatment beyond that provided in the
      clinical trial, with a median time to additional treatment from intake of 7.2
      months. The rates and times to additional treatment were similar in the 3
      treatment groups, despite the superior efficacy of cognitive-behavioral therapy
      in the acute phase. The severity of the index depressive episode and comorbid
      dysthymia were a predictor of additional treatment in the acute phase, whereas in
      the follow-up period the severity of depressive symptomatology, the presence of
      disruptive disorders, and family problems predicted additional treatment.
      CONCLUSIONS: Subsequent clinical trials for early-onset depression must focus on
      the entire depressive episode, rather than just the acute phase, to prevent
      depressive relapse. In addition, attendant family difficulties and comorbid
      behavioral problems must be addressed.

PMID- 10087688
TI  - Cognitive-behavioral treatment of adolescent depression: efficacy of acute group
      treatment and booster sessions.
AB  - OBJECTIVE: This trial examined the effects of both acute and maintenance
      cognitive-behavioral therapy (CBT) for depressed adolescents. METHOD: Adolescents
      with major depression or dysthymia (N = 123) were randomly assigned to 1 of 3
      eight-week acute conditions: adolescent group CBT (16 two-hour sessions);
      adolescent group CBT with a separate parent group; or waitlist control.
      Subsequently, participants completing the acute CBT groups were randomly
      reassigned to 1 of 3 conditions for the 24-month follow-up period: assessments
      every 4 months with booster sessions; assessments only every 4 months; or
      assessments only every 12 months. RESULTS: Acute CBT groups yielded higher
      depression recovery rates (66.7%) than the waitlist (48.1%), and greater
      reduction in self-reported depression. Outcomes for the adolescent-only and
      adolescent + parent conditions were not significantly different. Rates of
      recurrence during the 2-year follow-up were lower than found with treated adult
      depression. The booster sessions did not reduce the rate of recurrence in the
      follow-up period but appeared to accelerate recovery among participants who were
      still depressed at the end of the acute phase. CONCLUSIONS: The findings, which
      replicate and expand upon a previous study, support the growing evidence that CBT
      is an effective intervention for adolescent depression.

PMID- 10087689
TI  - Influence of parental concordance for psychiatric disorders on psychopathology in
      offspring.
AB  - OBJECTIVE: To examine the influence of parental mating types for substance abuse
      and anxiety/affective disorders on the risk of psychopathology among child and
      adolescent offspring. METHOD: Emotional and behavioral disorders were assessed in
      offspring, aged 7 to 17 years, of male and female parents who served as probands
      from a family study of comorbidity of substance abuse and anxiety disorders.
      RESULTS: The findings indicated that (1) patterns of psychopathology among
      offspring were similar for mothers and fathers; (2) spouse concordance for
      psychopathology was greater among parents with substance abuse than among those
      with anxiety, particularly among female substance abusers; (3) there was a direct
      relationship between the number of affected parents and the magnitude of
      psychopathology in children, particularly with respect to the anxiety disorders;
      and (4) by contrast, rates of conduct disorder were elevated only among offspring
      of dually affected parents, irrespective of the specific parental disorders.
      CONCLUSIONS: These findings underscore the importance of the contribution of both
      mothers and fathers, particularly those with concordance for psychiatric
      disorders, to the development of psychopathology in offspring.

PMID- 10087690
TI  - Grandparents, parents, and grandchildren at high risk for depression: a three
      generation study.
AB  - OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring
      that include 3 generations are uncommon. Multigenerational studies can be
      clinically useful as they can provide information for risk prediction from one
      generation to another for the development of empirically based interventions.
      Using a high-risk design, this study examines the association of grandparent
      major depressive disorder (MDD) and parent MDD with psychopathology in
      grandchildren. METHOD: Using Cox proportional hazards in a sample of 90
      grandchildren at high and low risk for depression by virtue of their
      grandparents' and parents' depression status, the authors examined the risk for
      offspring depression and anxiety. RESULTS: Grandparent and parent MDD were
      associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09,
      respectively). Grandchildren with both a depressed parent and grandparent had the
      highest risk for anxiety. Parental MDD is associated with an increased risk for
      grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the
      grandchildren in families in which both the parent and grandparent were depressed
      had some form of psychopathology. The grandchildren from those families were the
      most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor
      for the later development of clinically significant recurrent MDD across several
      generations of families at high risk for depression. Parental impaired
      functioning increases the risk for disruptive disorders. Children in families
      with multiple generations of depression are at particularly high risk for some
      form of psychopathology.

PMID- 10087691
TI  - Gay, lesbian, and bisexual youth risks for emotional, physical, and social
      problems: results from a community-based survey.
AB  - OBJECTIVE: Health problems of gay, lesbian, and bisexual (GLB) youth are reported
      as differing from those of heterosexual youth. Increased depression, suicide,
      substance use, homelessness, and school dropout have been reported. Most studies
      of GLB youth use clinical or convenience samples. The authors conducted a
      community school-based health survey that included an opportunity to self
      identify as GLB. METHOD: An anonymous self-report health care questionnaire was
      used during a community-based survey in 2 high schools in an upper middle class
      district. RESULTS: Significantly increased health risks for self-identified GLB
      youth were found in mental health, sexual risk-taking, and general health risks
      compared with self-identified heterosexuals, but not in health domains associated
      with substance abuse, homelessness, or truancy. CONCLUSIONS: Self-identified GLB
      youth in community settings are at greater risk for mental health, sexual risk
      taking, and poorer general health maintenance than their heterosexual peers.

PMID- 10087692
TI  - Psychiatric hospital service utilization of children and adolescents in state
      custody.
AB  - OBJECTIVE: To examine factors related to psychiatric hospitalization decision and
      length of stay of wards of the illinois Department of Child and Family Services.
      METHOD: A prospective design was implemented using the Childhood Severity of
      Psychiatric Illness (CSPI), a reliable, quantitative measure of psychiatric
      severity and its mediating factors. The CSPI was completed by hospital screeners
      upon conclusion of their crisis interviews. In addition to completing the CSPI,
      workers reported on demographic information, DSM-IV diagnoses, prescreening
      living arrangements, and length of hospital stay. RESULTS: CSPI variables could
      effectively predict decision to admit versus deflect. The overall accuracy of
      this statistically significant prediction model was 77.9%, which was replicated
      on a new sample. Factors associated with decision to hospitalize are clinical in
      nature; ratings of suicidality, dangerousness, and impulsivity contributed the
      most to the model. Predicting length of stay was only moderately successful.
      Despite achieving significance, the model accounted for just 15.1% of length of
      stay variance using a multiple regression. Factors associated with length of stay
      were largely nonclinical in nature: living arrangement stability, region of the
      hospitalization, and age. CONCLUSIONS: These results can be used to assess how
      decisions regarding level and duration of care are currently being made as a
      point of departure for quality improvement efforts.

PMID- 10087693
TI  - Deficient social problem-solving in boys with ODD/CD, with ADHD, and with both
      disorders.
AB  - OBJECTIVE: To study social problem-solving skills in psychiatrically defined
      aggressive boys, starting from Dodge's social information-processing model.
      METHOD: Videotaped stimuli of problematic social situations and questions were
      presented to elicit responses that indicate boys' social problem-solving skills
      (encoding and interpretation of social cues, generation of possible responses,
      evaluation of responses, self-efficacy evaluation, and response selection). Boys
      aged 7 to 12 years with oppositional defiant or conduct disorder (ODD/CD) (n =
      48), attention-deficit hyperactivity disorder (ADHD) (n = 27), and both disorders
      (ODD/CD + ADHD) (n = 29) were involved as well as a normal control group (n = 37)
      and a psychiatric control group with internalizing disorders (n = 23). RESULTS:
      When compared with normal controls, boys with ADHD, with ODD/CD, and with ODD/CD
      + ADHD encoded fewer social cues and generated fewer responses. Boys with ODD/CD
      and with ODD/CD + ADHD moreover were more confident in their ability to enact an
      aggressive response than normal controls. When ODD/CD boys and ODD/CD + ADHD boys
      were given the opportunity to select a response from various types of responses
      shown, they selected an aggressive response more often than normal controls.
      Thus, in ADHD boys social problem-solving was affected only in encoding and in
      the generation of responses, whereas in ODD/CD and ODD/CD + ADHD boys social
      problem-solving was affected throughout the process. CONCLUSION: For the further
      study of social problem-solving in aggressive children, it is essential to
      differentiate between children with ADHD and children with ODD/CD and ODD/CD +
      ADHD.

PMID- 10087694
TI  - The third factor of the WISC-III: it's (probably) not freedom from
      distractibility.
AB  - OBJECTIVE: This study examined the ecological validity, construct validity, and
      diagnostic utility of the third factor of the WISC-III, heuristically labeled
      "Freedom From Distractibility" (FFD). METHOD: A sample of 200 children, aged 6 to
      11 years, with attention-deficit hyperactivity disorder (ADHD) completed the WISC
      III, the Wide Range Achievement Test-Revised, and the Test of Variables of
      Attention. Objective parent and teacher report measures of attention and
      hyperactivity were completed. RESULTS: Mean FFD scores were significantly lower
      than other WISC-III factor scores. The diagnostic utility of FFD is limited,
      however, as the majority of these children did not show a significant relative
      weakness on this index. Correlational analyses failed to support the concurrent,
      ecological, or construct validity of the FFD. FFD scores were not correlated with
      a measure of sustained visual attention. Findings suggest that among children
      with ADHD, a low FFD score may be associated with the presence of a learning
      disability or poor academic performance. This finding was maintained after level
      of general intelligence was statistically controlled. CONCLUSIONS: Clinicians and
      researchers should not view FFD as a reliable or valid index of attention or as a
      diagnostic screening measure for identifying children with ADHD.

PMID- 10087695
TI  - Obsessive-compulsive symptoms in Prader-Willi and "Prader-Willi-Like" patients.
AB  - OBJECTIVE: To compare obsessive-compulsive (OC) symptoms in patients with Prader
      Willi syndrome (PWS) and symptoms in a group of patients presenting with "Prader
      Willi-like" features but without the genetic abnormalities associated with PWS.
      METHOD: 16 patients aged 4 through 20 years were evaluated in a clinic
      specializing in the assessment and management of behavioral and food-related
      problems in PWS. Eight patients were found to have key features of the syndrome
      but did not have a PWS genotype. These PWS-like subjects were matched to 8 clinic
      patients with a confirmed deletion of the PWS critical region of the paternally
      derived chromosome 15. All subjects were evaluated for obesity, IQ, food-related
      problems, maladaptive behaviors, and non-food-related OC symptoms. RESULTS: There
      were no differences between the 2 groups with respect to measures of obesity, IQ,
      food-related difficulties, or overall maladaptive behaviors. The PWS group showed
      significantly greater numbers of OC symptoms and greater symptom severity.
      CONCLUSIONS: Patients with PWS have elevated numbers of OC symptoms and
      significant symptom-related impairment which are not explained by developmental
      delay, food-related difficulties, or obesity. OC symptoms are part of a
      behavioral phenotype that accompanies deletions on the proximal long arm of
      chromosome 15 in PWS.

PMID- 10087696
TI  - Case study: carbamazepine treatment of juvenile-onset bipolar disorder.
AB  - The literature devoted to juvenile-onset bipolar disorder has rapidly expanded in
      the past 5 years with an emphasis on new concepts of prevalence and comorbid
      conditions. In the process of enlarging the knowledge base about the
      phenomenology of juvenile-onset bipolar disorder, this new literature has
      generated considerable controversy but has provided little information about
      pharmacotherapy. In the following case series, carbamazepine appeared to be a
      safe and effective treatment for juvenile-onset bipolar disorder. Controlled
      studies are necessary before any definitive conclusions can be reached about the
      efficacy of carbamazepine in the treatment of this form of bipolar disorder.

PMID- 10087697
TI  - The 3 R's of school consultation.

PMID- 10087698
TI  - A tale of two paradigms.

PMID- 10087699
TI  - Development of the cerebral cortex: XV. Sexual differentiation of the central
      nervous system.

PMID- 10087700
TI  - Flying Doctors of America--a volunteer's experience.

PMID- 10087701
TI  - Madison physicians give of their time and of their mind.

PMID- 10087702
TI  - How Hospice Atlanta, Inc. came into its own.

PMID- 10087704
TI  - Ministry in your own backyard.

PMID- 10087703
TI  - A community of caring.

PMID- 10087705
TI  - Healing without housing: the Open Door Community's medical clinic.

PMID- 10087706
TI  - Tremendous benefits.

PMID- 10087707
TI  - Charity programs at the Center for Craniofacial Disorders Scottish Rite
      Children's Medical Center.

PMID- 10087708
TI  - The physician volunteer.

PMID- 10087709
TI  - Medical missions.

PMID- 10087710
TI  - Savannah doctors lead nation in United Way giving.

PMID- 10087711
TI  - Mercy Mobile Health Care.

PMID- 10087712
TI  - Tifton physicians volunteer at home and abroad.

PMID- 10087713
TI  - Mission focused. How Egleston Children's Health Care System and Scottish Rite
      Children's Medical Center work to provide charity care for children.

PMID- 10087714
TI  - Epidemiology of persistent tuberculosis in DeKalb County, Georgia, 1990-1996.
AB  - BACKGROUND: In DeKalb County, Georgia, during 1990 to 1996, tuberculosis
      incidence rates fluctuated between 15.3 cases/100,000 person-years (PY) and 19.2
      cases/100,000 PY. These rates are approximately 1.5 to 2 times higher than those
      measured for the United States as a whole, and do not reflect the decline
      observed nationally since 1993. We reviewed DeKalb tuberculosis registry to
      investigate risk factors for tuberculosis and describe trends of tuberculosis
      incidence over time. METHODS: We compared average annual tuberculosis case counts
      and incidence rates in DeKalb before and after 1993. We calculated rates of
      tuberculosis incidence using race, age and sex stratified population estimates
      from the U.S. Bureau of the Census. We compared these rates for the periods 1990
      1992 and 1993-1996 using Poisson regressions. RESULTS: Between both time periods,
      tuberculosis case counts decreased by 6% among whites, by 2% among blacks, and
      increased by 34% among Asians. Despite this large increase in case numbers,
      tuberculosis incidence rates among Asians only increased by 4%. For all three
      race groups, tuberculosis incidence almost doubled for those younger than 15
      years of age. CONCLUSIONS: Trends of tuberculosis incidence in DeKalb County
      varied between different population groups. Migration from countries with a high
      prevalence of tuberculosis accounted for a larger number of foreign-born cases in
      recent years. However, increasing tuberculosis incidence rates found among the
      youngest age groups suggest that active transmission of Mycobacterium
      tuberculosis also took place.

PMID- 10087715
TI  - Screening for depression.

PMID- 10087716
TI  - Atrial myxoma: a review of clinical experience at Srinagarind Hospital.
AB  - Thirty-two intracardiac myxoma patients who underwent tumor excision in
      Srinagarind Hospital between January 1, 1983 and January 30, 1997 were
      retrospectively reviewed. Clinical presentations, diagnostic method, operative
      findings, and postoperative course were also analysed. There were 20 female and
      12 male patients, age range 10 to 60 years (mean 37.9). Clinical presentations
      included congestive heart failure (56.2%), atypical chest pain (25.0%), syncope
      (18.9), and constitutional symptoms (9.3%). In six patients, there was clinical
      evidence of systemic embolism. One patient was essentially asymptomatic and
      incidentally detected during clinical check-up. Diagnosis was all made by two
      dimensional (2-D) echocardiographic study. There were 29 left atrial, 2 right
      atrial and 1 combined right atrial and right ventricular myxomas. There were 3
      postoperative deaths, two due to septicemia and the other due to cerebral
      embolism. One patient developed postoperative severe mitral regurgitation and
      complete heart block needed mitral valve replacement and permanent pacemaker
      insertion. One patient developed localized seizure 6 years after resection and
      was suspected of brain metastasis. The other was found to have two high echogenic
      liver masses, 2 years after resection, suggestive of hepatic metastasis.
      Unfortunately, we could not obtain the histologic confirmation from any of those
      suspected lesions. Because of the non-specific and various manifestations of
      atrial myxoma, a high index of suspicion is needed. The diagnostic method of
      choice is 2D-echocardiography. Clinical follow-up for at least 10 years may be
      needed to rule out recurrence or metastasis.

PMID- 10087717
TI  - Estradiol and follicle-stimulating hormone levels in oophorectomized women
      applying percutaneous 17 beta-estradiol over the medial surface of the left arm.
AB  - To assess the changing estradiol (E2) and follicle stimulating hormone (FSH)
      level in oophorectomized women applying percutaneous 17 beta estradiol over the
      medial surface of the left arm. Thirty-nine women, who had undergone total
      abdominal hysterectomy and bilateral oophorectomy after 4 weeks, were enrolled
      into the study. All subjects received a daily dose of 1.5 mg percutaneous 17 beta
      estradiol in 2.5 g of the gel, applied over the medial surface of the left arm in
      the limited area of 150 cm2. Serum E2 and FSH were measured before and after
      commencing the study at weeks 4, 8 and 12. The measurement was performed 12-14
      hours after the gel application, using time-resolved fluoroimmunoassay (FIA)
      method. Serum E2 significantly increased from the baseline value at weeks 4, 8
      and 12 (Median of E2 value at weeks 0, 4, 8 and 12 = 47.30, 86.78, 128.00 and
      163.15 pmol/L, respectively, P < 0.05). While the serum FSH level significantly
      decreased. (Median of FSH value at weeks 0, 4, 8 and 12 = 66.05, 60.40, 53.35 and
      48.40 IU/L, respectively, P < 0.05). In conclusion, this dose, duration and route
      of estrogen administration increased the serum E2 level close to the early to mid
      follicular phase of the normal menstrual cycle. While FSH level significantly
      decreased but did not reach the premenopausal range.

PMID- 10087718
TI  - Histologic types, staging, resectability, and smoking among Thai patients with
      lung cancer.
AB  - AIM: To examine the prevalence of cigarette smoking, histological types, staging
      at presentation and resectability among Thai patients with lung cancer. SETTING:
      A 500-bed referral cardiothoracic centre. METHOD: Prospective study with pre
      defined outcome data, from January to December 1996. RESULTS: A total of 349
      patients were histologically proved to have lung cancer. The mean age was 60
      years (SD 12.5). There were 264 males and 85 females. 269 patients (77%) were
      smokers. Percentage of histopathologic types were 39 per cent adenocarcinoma, 30
      per cent squamous cell carcinoma, 20 per cent undifferentiated cell carcinoma,
      and 11 per cent small cell carcinoma. The association with smoking is stronger in
      squamous cell carcinoma and small cell carcinoma and weaker in adenocarcinoma.
      Most patients (82%) were in advanced stages, stage 3B and 4.18 per cent of the
      patients were in stages eligible for surgery, i.e. stage 1, 2 and 3A. However,
      only 9.7 per cent of the patients were operable and 9.1 per cent were resectable.
      CONCLUSIONS: On reaching the diagnosis, most patients with lung cancer were in
      advanced stages of the disease, rendering a low resectability. The results
      emphasise the need for early diagnostic intervention in patients presenting with
      lung mass. Furthermore, preventive measures including a campaign against
      cigarette smoking, research into other possible aetiological factors should be
      more encouraged.

PMID- 10087719
TI  - Mandibular reconstruction: free flap vs AO plate.
AB  - The purpose of this study was to compare the use of the AO reconstruction plate
      with immediate free vascularized bone graft mandibular reconstruction. From April
      1989 to December 1993 we performed 13 cases of mandibular reconstruction.
      Reconstruction plates were used in 4 and immediate free bone grafts were used in
      9 patients. The overall success rate for use of the plate was 2 of 4 (50%). In
      one of the plate failure patients, the plate was removed eight months
      postoperatively. She was able to wear a dental prosthesis. Cancer destruction and
      microvascular anastomosis of the first seven free flaps were performed by one
      surgical team. Only 4 free flaps were successful (success rate was 44%). We found
      that the use of AO plate with flap for lateral defect was relatively safe,
      simple, functional, time-saving, cosmetically acceptable and could be used
      successfully in post-operative irradiated patients. Success rate of the free flap
      was better with two surgical teams. The long-term result of the free flap was
      more reliable than the AO plate.

PMID- 10087720
TI  - Screening assessment of persons 40-59 years of age in rural Thailand by a mobile
      health unit.
AB  - This paper reports a screening survey using a mobile unit to determine the
      prevalence of chronic disorders among persons aged 40-59 years in rural Thailand.
      A total of 4,812 persons from all the 54 rural villages in Mae Sot District, Tak
      Province, northern Thailand, were interviewed and examined in 1995. A higher
      proportion (59.3%) of men were current tobacco smokers than among women (40.4%).
      A higher proportion (69.6%) of men were current alcohol drinkers compared with
      women (38.6%). Cutting/piercing was the most frequently reported injury, followed
      by falls. About half (47.9%) of the persons surveyed had a body mass index (BMI)
      between 20 and 24.9 and only 2.6 per cent had a BMI of 30 or over. The overall
      prevalence rates of hypertension and diabetes in the persons surveyed were 13.3
      per cent and 2.4 per cent respectively. Of the persons screened, 28.8 per cent
      had borderline-high blood cholesterol (200-239 mg/dl) and 12.9 per cent had high
      blood cholesterol (> or = 240 mg/dl). About 61 per cent of hypertensive persons,
      92 per cent of diabetic persons, and nearly all of those with dyslipidaemia were
      first detected during this screening programme. Five women with breast cancer and
      22 with benign breast disorders were also identified during the survey. A
      screening programme using a mobile unit may be useful in identifying treatable
      disorders in rural areas, where existing screening services cannot effectively
      cover the population at risk.

PMID- 10087721
TI  - Frequency of angina pectoris and coronary artery disease in severe isolated
      valvular aortic stenosis.
AB  - Angina pectoris is a frequent symptom of severe valvular aortic stenosis (AS),
      even in the presence of normal coronary arteries. To determine the prevalence of
      angiographically significant coronary artery disease (CAD) and its relation to
      angina pectoris and coronary risk factors in severe isolated valvular AS
      patients. All cases of symptomatic AS patients who underwent aortic valve
      replacement and preoperative cardiac catheterization at the Central Chest
      Hospital between January 1, 1986 and December 31, 1996 were retrospectively
      analyzed. Excluded were those with multiple valvular disease, aortic
      regurgitation of grade 2 or more, and prior coronary or valve surgery. A total of
      ninety consecutive patients with severe AS (64 men and 26 women, mean age 58.94
      years, range 38 to 71) were studied. Significant CAD (coronary diameter stenoses
      > or = 50%) was found in 15 patients (16.7%). Typical angina was present in 66.7
      per cent of them but it was also found in 46.7 per cent of the non-CAD patients.
      This symptom had low positive predictive value (22%). Of the patients without
      angina (n = 45) 11.1 per cent had significant CAD, The negative predictive value
      of angina alone was thus 89 per cent. By univariate logistic regression, the
      statistically significant variables to discriminate those with or without
      significant CAD were age, history of hypertension, positive familial history of
      premature CAD, and cholesterol level. However, only age and hypertension were
      statistically significant by multivariate logistic regression analysis. Coronary
      arteriography can probably be omitted in severe valvular AS, especially those
      without a history of hypertension and < 40 years of age in men and < 50 years in
      women. For all other cases, coronary arteriography is recommended. In our study,
      angina pectoris is not a significant predictor for associated CAD.

PMID- 10087722
TI  - Possible thermogenesis with dexfenfluramine.
AB  - Fifty obese patients with a body mass index greater than 25 kg/m2 were randomized
      into 3 groups: control (C = 19), placebo (P = 18) and dexfenfluramine (D = 18). A
      behavioral modification program which included eating habits, exercise,
      attitudes, social relationships and six steps to lifetime weight control was
      taught every week. All patients strictly followed the food manual and recorded
      their behavior, physical activity and food intake every day through 12 weeks.
      Placebo and dexfenfluramine 30 mg/day were given in a double blind placebo
      controlled study. The results showed that all 3 groups had significant decreases
      in rest times and increased activity times (p < 0.05) and significant reductions
      of the average total daily energy, carbohydrate and fat intake (p < 0.05). They
      all lost weight. Mean +/- SEM cumulative weight loss was 8.3 +/- 0.7 kg in group
      D, 3.3 +/- 1 kg, in group P and 2.9 +/- 0.7 kg, in group C. The mean additional
      weight loss of 5 kg, and 5.4 kg seen with dexfenfluramine being highly
      significant (p < 0.001) from group P and C most likely due to increased
      thermogenesis. Significant (p < 0.05) and gradual reduction of biceps, triceps
      skinfold and per cent body fat were constantly observed only in the
      dexfenfluramine group. There were no significant differences among the 3 groups
      regarding blood pressure, heart rate, hematologic, lipids and biochemical
      profiles.

PMID- 10087723
TI  - Structural shared care (long-term continuity of care) for patients with chronic
      diseases.
AB  - The long-term management of patients with chronic disease is the main problems of
      care. Structural shared care is one of the health care schemes whose purposes are
      the continuity of care for chronic disease by systematic approach that is
      integration of services with primary and secondary care.

PMID- 10087724
TI  - The expression of cyclooxygenase-2 in human umbilical vein endothelial cell
      culture from preeclampsia.
AB  - We have shown the HUVEC from normal pregnancy contained COX-1 protein but not COX
      2 protein and released 6-keto-PGF1 alpha 277 +/- 5 ng/ml (for 24 h). In contrast,
      HUVEC from preeclampsia contained both COX-1 and COX-2 protein and released
      significantly lesser amounts of 6-keto-PGF1 alpha (159 +/- 8 ng/ml for 24 h; p <
      0.05). Thus, COX-2 is expressed in HUVEC from preeclampsia but not in normal
      pregnancy and affects the release of prostacyclin suggesting the involvement of
      COX-2 in the pathogenesis of preeclampsia. The development of selective
      inhibitors of COX-2 may have a potential role in prevention and treatment of
      preeclampsia.

PMID- 10087725
TI  - Comparison of ondansetron and placebo for preventing postoperative nausea and
      emesis in gastrointestinal tract surgery: a multicenter randomized controlled
      trial.
AB  - BACKGROUND: Nausea and emesis are undesirable events that may cause discomfort
      and suffering in the postoperative period. This study was carried out to evaluate
      the efficacy and safety of ondansetron for preventing postoperative nausea and
      vomiting in patients undergoing gastrointestinal tract surgery. METHODS: Using a
      randomized double-blind study design, 408 surgical patients (163 male and 245
      female) receiving general endotracheal anesthesia were studied at five medical
      centers in Bangkok. Ondansetron (4 mg) or placebo was administered prior to
      induction of anesthesia. Episodes of nausea and vomiting, adverse events and
      laboratory tests (complete blood count and liver function test) were evaluated
      during 24 hours after study drug administration. RESULTS: The incidence of
      postoperative nausea and vomiting in the placebo group (42.7 and 35.2%) were
      significantly higher than the ondansetron group (23.9 and 15.4%). However, no
      significant differences occurred in the incidence of adverse events or changes in
      laboratory tests in the ondansetron group compared to the placebo group.
      CONCLUSIONS: Ondansetron 4 mg given intravenously before surgery is safe and
      effective for preventing postoperative nausea and emesis following
      gastrointestinal tract surgery.

PMID- 10087726
TI  - Plasma zinc level and intrauterine growth retardation: a study in pregnant women
      in Ramathibodi Hospital.
AB  - The study was designed to establish the relationship between plasma zinc level
      and intrauterine growth retardation in 405 normal pregnant women with an age
      range from 20 to 35 years, who attended and delivered at Ramathibodi Hospital The
      data were gathered from October 1994 to April 1995. The zinc levels were obtained
      from blood plasma collection and the assessment of fetal status was made after
      birth. Using criteria of babies with a birthweight of less than the 10th centile
      at delivery. Plasma zinc level in mother was collected during antenatal care and
      labour. Plasma zinc level was determined by Atomic Absorption Spectrophotometry.
      The plasma zinc levels in mothers during antenatal care, labour and infant
      birthweight were 66.73 micrograms/dl, 69.91 micrograms/dl and 3152.25 g
      respectively. Maternal plasma zinc levels during antenatal care, labour and
      infant birthweight in the intrauterine growth retardation infant group were
      significantly lower than that in normal growth infants (P < 0.05). In conclusion,
      our study shows that measurement of maternal plasma zinc concentration in the
      third trimester would highly suggest mothers at risk of delivering intrauterine
      growth retardation babies. Mothers selected in this way might benefit from
      dietary advice and zinc supplementation during the remaining pregnancy.

PMID- 10087727
TI  - The relationship between body mass index and the number of sides of carpal tunnel
      syndrome.
AB  - The prospective study was performed in 250 patients with carpal tunnel syndrome.
      The mean body mass index (BMI) of patients with bilateral carpal tunnel syndrome
      was more than that of patients with unilateral carpal tunnel syndrome (t = 6.84,
      p < 0.001). There was no statistically significant difference between the mean
      BMI of patients with right carpal tunnel syndrome and that of patients with left
      carpal tunnel syndrome. In conclusion, BMI may be used to predict the number of
      sides of carpal tunnel syndrome.

PMID- 10087728
TI  - Anatomical landmark for internal jugular vein catheterization for detection of
      jugular venous O2 saturation (SjvO2) in Thai people.
AB  - Thirty-two (32) cadavers were dissected to find the anatomical landmark for
      puncturing the internal jugular vein. The point for the right internal jugular
      vein was 2 cm above and 2.17 cm lateral to the right clavicular head, and that
      for the left internal jugular vein was 2 cm above and 2.08 cm lateral to the left
      clavicular head. The right internal jugular vein was found to dominate eighty
      eight per cent (88%) of the cadavers. The anatomical point 2 cm above and 2 cm
      lateral to the head of the clavicle was appropriate for puncturing the internal
      jugular vein. After puncturing the internal jugular vein, a catheter was inserted
      ascending to the jugular bulb where jugular venous O2 saturation (Sjv O2) related
      to the cerebral metabolism was detected.

PMID- 10087729
TI  - Hormonal ablation therapy for metastatic prostatic carcinoma: a review.
AB  - Hormonal therapy is the standard treatment for metastatic prostatic carcinoma.
      The conventional surgical or medical androgen ablation therapy seems to have a
      similar response. Despite a higher response of CAB compared to conventional
      castration in metastatic disease, the controversy of survival benefit remains
      unsolved. Immediate treatment should be given in metastatic disease particularly
      in patients who have minimal metastases. In patients who have progression after
      CAB, antiandrogens should be withdrawn. The choices of optimal therapies for
      prostate cancer depend not only on the survival but also the quality of life and
      cost effect. Thus, the critical factors for approaching prostate cancer are
      appropriate patient selection and stratification. Implicit with this approach
      should maximize benefit from maximal androgen ablation therapy for patients who
      are likely to profit from it. Finally, the development of experiments, clinical
      trials, and novel therapeutic strategies may provide better management for
      prostate cancer in the future.

PMID- 10087730
TI  - "Lack of ethics" petition against physicians through the Council of State Act.

PMID- 10087731
TI  - Exchange transfusion in severe falciparum malaria.
AB  - Malaria associated with complications or a fatal outcome is caused by Plasmodium
      falciparum. The mortality due to this disease is parallel to the degree of
      parasitemia. Successful use of exchange blood transfusion as a therapeutic
      adjunct for this infection was reported. The rationale for this form of therapy
      is based on (1) rapid reduction in parasite load by exchange transfusion, (2)
      removal of toxic substances and (3) reducing microcirculatory sludging. We
      describe here thirteen cases of severe falciparum malaria treated with infusion
      of quinine dihydrochloride and exchange transfusion 2,320-8,000 ml of whole
      blood. We observed that the greatest reduction in the average circulating
      infected red blood cells, from 20.7 per cent to 9.3 per cent, seemed to occur
      early in the first 2,000 ml of blood exchange and the parasitemia often reduced
      to 5.1 per cent in patients who had 4,000 ml of blood exchange. In order to
      reduce the initial parasitemia to 5 per cent by exchange transfusion, we suggest
      the volume of exchange transfusion should be 2,000 ml for average parasitemia 10
      per cent, 4,000 ml for parasitemia > 20 per cent and 2,000-4,000 ml for
      parasitemia 10-20 per cent.

PMID- 10087732
TI  - Clinical effects of gestrinone for the treatment of pelvic endometriosis in
      infertile patients.
AB  - The clinical efficacy and side effects of oral gestrinone, 2.5 mg twice weekly,
      were evaluated in this prospective study involving 22 patients with
      laparoscopically confirmed endometriosis. All patients came to the hospital with
      infertility problem. After 6 months of treatment, 81 per cent of patients had
      amenorrhea. Dysmenorrhea and pelvic pain were reduced from 90.9 per cent to 14.3
      per cent and 81.8 per cent to 9.5 per cent respectively. Pelvic tenderness and
      induration were improved from 55.6 per cent and 50.0 per cent to 15.8 per cent
      and 10.5 per cent respectively. Androgenic effects such as acne was founded in
      18.2 per cent of the patients. Return of fertility was observed in 25 per cent (5
      patients) after 30-254 days post treatment. No serious side effect was detected
      during the treatment. The results suggest that gestrinone may be considered an
      option for the treatment of endometriosis related infertility.

PMID- 10087733
TI  - Malignant ascites in female patients: a seven-year review.
AB  - Malignant ascites is common in various types of advanced cancer. Our objective
      was to determine the primary site and the clinical characteristics of female
      patients presenting with malignant ascites as well as evaluating the outcome. The
      authors carried out a retrospective study of 118 cases of malignant ascites
      diagnosed from January 1986 to December 1992 in female patients. Of the 118
      cases, the primary site of the neoplasms was gynecologic in 65 cases (cervix 4,
      endometrium 6, ovary 52, fallopian tube 3) = 55.1 per cent, non-gynecologic 29
      cases (GI 18, lymphoma 8, breast 2, kidney 1) = 24.6 per cent, and unknown 24
      cases = 20.3 per cent. The mean age of patients in the gynecologic, non
      gynecologic and unknown primary site was 50.4, 45.5 and 59.3 years respectively.
      Surgery combined with chemotherapy was the main treatment in the gynecologic
      group, whereas, supportive and symptomatic management was the main treatment in
      the unknown primary group. Treatments in non-gynecologic group were supportive
      and symptomatic, surgery and chemotherapy. Survival was longer in gynecologic
      than in the nongynecologic and the unknown primary groups. The most common
      primary site of malignant ascites in females was ovarian cancer. In malignant
      ascites in females caused by gynecologic neoplasms, the prognosis as measured by
      survival was better than in the non-gynecologic and the unknown primary groups.

PMID- 10087734
TI  - Endoscopic third ventriculostomy.
AB  - We prospectively studied 8 patients who had an endoscopic third ventriculostomy
      performed between 1996 and 1997 in Songkhlanagarind Hospital. The surgical
      technique was described. Seven operations were successful and one operation
      failed. Success was found in cases of pure aqueductal stenosis, aqueductal
      stenosis with Dandy Walker malformation, and posterior fossa tumor. In a patient
      where an endoscopic third ventriculostomy failed, aqueductal stenosis with marked
      hydrocephalus was found. Marked dilation of the third ventricle could compress
      the aqueduct of Sylvius. Although there was communicating hydrocephalus, it
      looked like non-communicating hydrocephalus. To avoid a valvular shunting
      complication, we suggest performance of an endoscopic third ventriculostomy in
      selected non-communicating hydrocephalus patients.

PMID- 10087735
TI  - Female genital tuberculosis: clinical features and trend.
AB  - A retrospective study of genital tuberculosis in women attending the Department
      of Obstetrics and Gynecology between January 1986 and December 1997 revealed 11
      patients with a mean age of 38 years (range 23-77). Two patients had genital
      tuberculosis and tuberculous peritonitis. The incidence was 0.01 per cent of
      outpatients and 0.05 per cent of inpatients. Eight cases occurred during the last
      six years. Although the incidence was quite low, a rising trend was observed. Of
      the clinical features, infertility was the commonest initial symptom (3 cases).
      The most common site of infection was the endometrium (5 cases) followed by
      fallopian tube and ovary (3 cases). Chest X-ray of all patients showed no lung
      infiltration while AFB staining and PCR for tuberculosis were positive in two out
      of five and one out of two respectively. Six patients received medical treatment
      only, and three were treated with antituberculous drugs after surgery; all with
      good results. Tubal reconstructive surgery was performed in two patients without
      medical treatment. Gynecologists should be aware of this disease to facilitate
      early diagnosis and treatment.

PMID- 10087736
TI  - Management of endometrial hyperplasia: a retrospective analysis.
AB  - OBJECTIVE: To determine the incidence of endometrial hyperplasia and to analyse
      the management of patients with this disorder. METHOD: Retrospective descriptive
      study at the Department of Obstetrics and Gynecology, Ramathibodi Hospital. The
      medical records of patients with endometrial hyperplasia from 1990 to 1995 were
      analysed. Descriptive statistic was used. RESULT: Medical records could be
      obtained in 87 per cent of cases. Incidence of endometrial hyperplasia was 1 per
      cent of gynecological out-patients and 11 per cent of uterine curettage. Half of
      the patients had cystic hyperplasia. Main treatment options of patients with
      cystic hyperplasia were expectant and progestogen therapy. The major treatments
      of adenomatous hyperplasia were progestogen and hysterectomy. Most patients with
      atypical hyperplasia underwent hysterectomy. Most of the patients with expectant
      or hormonal therapy have recurrence of abnormal uterine bleeding. CONCLUSION:
      Endometrial hyperplasia is not uncommon in gynecological practice. All
      gynecologists should be familiar with the pathophysiology and the natural history
      of this disorder. The unopposed estrogen stimulation should be investigated and
      corrected. Treatment options should be tailored to individuals according to
      disease grading, age of the patient and desire of pregnancy. Long-term follow-up
      until menopause is mandatory to prevent the excessive uterine blood loss and the
      progression to carcinoma.

PMID- 10087737
TI  - Effects of general and regional anesthesia on the neonate (a prospective,
      randomized trial).
AB  - Anesthetic methods used during cesarean section have advantages and disadvantages
      to both mothers and infants and may result in short and long term neonatal
      effects. OBJECTIVE: To determine the effects of general and regional anesthesia
      on the infants, a prospective, randomized trial was performed in Siriraj
      Hospital, Mahidol University. MATERIAL AND METHOD: 341 uncomplicated pregnant
      women who were to be delivered at term by Cesarean section were recruited and
      randomized to receive general anesthesia, GA (103); epidural anesthesia, EA (120)
      and spinal anesthesia, SA (118). The immediate fetal and neonatal effects were
      assessed by cord blood gas analysis and the infant's Apgar scores. The Neurologic
      and Adaptive Capacity Scores (NACS) was performed within 4 hours after birth by
      two pediatricians who were blind to the anesthetic method. RESULT: Maternal age,
      weight, height, duration of the operation and infants' birth weight were not
      different among the study groups. In the EA and SA group, maternal systolic blood
      pressure decreased more than 20 per cent from the baseline in more than half. The
      infants' Apgar scores at 1 and 5 minutes were 8.3 +/- 1.9; 8.2 +/- 1.6; 6.7 +/-
      2.8, and 9.7 +/- 0.9; 9.8 +/- 0.7; 9.2 +/- 1.6 in EA, SA and GA group
      respectively. The adaptive capacity, active tone, passive tone, general
      assessment and primary reflexes of the NACS were not statistically different.
      CONCLUSION: Apgar scores of the infants whose mothers received general anesthesia
      were lower than infants whose mothers received regional anesthesia but the NACS
      were not statistically different among the three study groups.

PMID- 10087738
TI  - Post-traumatic hydrocephalus: experience in 17 consecutive cases.
AB  - BACKGROUND: Ventriculomegaly after head injury is one of controversial debate.
      Currently there is no definite way to distinguish post-traumatic hydrocephalus
      (PTH) from cerebral atrophy. The favourable outcome is only from CSF shunting in
      patients with true post-traumatic hydrocephalus, not hydrocephalus exvacuo.
      METHOD: 17 patients with post-traumatic hydrocephalus were retrospectively
      reviewed from January 1993 to February 1996 to determine risk factors and
      guidelines for the management of this problem. RESULTS: These 17 patients
      represented 1.6 per cent of the 1080 head-injured patients seen at
      Songklanagarind Hospital during that period. 385 patients were classified as
      severe head injury in whom 7 were complicated with post-traumatic hydrocephalus.
      Our study found a high incidence of correlation between PTH and decompressive
      craniectomy. The late effect of decompressive craniectomy may cause CSF blockage
      around the convexities and hydrocephalus. The diagnoses were based on clinical
      manifestations and CT scan appearances. The outcome was related closely to the
      initial GCS score and the method used for diagnosis. CONCLUSION: Post-traumatic
      hydrocephalus was 1.8 per cent in patients with severe head injury. Late
      neurological deterioration confirmed by CT scan findings was more useful than CT
      scan findings alone. CSF shunting was effective in patients with ventriculomegaly
      who had clinical signs and symptoms of increased intracranial pressure from post
      traumatic hydrocephalus.

PMID- 10087739
TI  - Comparison of pronuclear stage embryo transfer and in vitro fertilization-embryo
      transfer following intracytoplasmic sperm injection.
AB  - To determine whether the mode of embryo transfer (PROST vs IVF) affected the
      outcome in intracytoplasmic sperm injection (ICSI) cycles, 237 ICSI cycles (106
      PROST and 131 IVF) were analyzed. Several parameters, including patient age,
      duration of infertility, amounts of hMG used, number of mature eggs retrieved and
      injected, fertilization rate, number of embryos transferred, and clinical
      pregnancy rate, were compared. Most of the variable factors were not
      significantly different, except the mean numbers of transferred embryos which
      were significantly higher in the PROST group. The clinical pregnancy rate showed
      no statistical difference between PROST and IVF cycles (25.5 and 16.8%; p =
      0.139). This study suggests that even the pregnancy rate in PROST cycles was
      slightly higher than IVF cycles, but there was no statistically significant
      difference between the two groups.

PMID- 10087740
TI  - Leber's hereditary optic neuropathy (LHON) with mitochondrial ND4 gene mutation
      (11778) in a Thai patient.
AB  - Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease,
      characterized by bilateral optic atrophy predominantly in healthy young males.
      This disorder has shown to be associated with DNA mutation in mitochondrial
      genome of the patients. We report here a young man who came to the hospital with
      subacute visual loss in one eye, followed by the other eye within two months. His
      echocardiogram was normal. A G-->A base substitution at nucleotide position
      11,778 which changes a conserved arginine to histidine at amino acid position 340
      of ND4, a protein subunit of respiratory chain enzyme complex I in oxidative
      phosphorylation system, was detected in his leucocyte mitochondrial genome.

PMID- 10087741
TI  - Serum cyrptococcal antigen: diagnostic value in the diagnosis of AIDS-related
      cryptococcal meningitis.
AB  - RATIONALE: The incidences of HIV-AIDS patients with opportunistic infections of
      the central nervous system are increasing. Of these, cryptococcal meningitis is
      the most important and serious. A simple method for the diagnosis of cryptococcal
      meningitis is needed despite its variable clinical features and the lack of a
      capacity in most health facilities in Thailand to exclude it from other diseases
      especially mass lesions in the brain. OBJECTIVE: To identify the capability and
      cut off point of serum cryptococcal antigen for diagnosis and screening of
      cryptococcal meningitis in HIV-AIDS patients. METHODS: One hundred consecutive
      cases of HIV-AIDS patients suspected of having central nervous system infections
      were prospectively recruited for the study. The serum of all patients were
      examined for cryptococcal antigen by latex agglutination test, the Pastorex
      Cryptococcus manufactured by Sanofi Diagnostic Pasteur, France. If a test was
      positive, the serum dilution was carried out using 10-fold serial dilution. Every
      patient went through pre-defined standard investigations to derive at a definite
      diagnosis. The gold standard for diagnosis of cryptococcal meningitis was the
      presence of encapsulated yeast forms in the cerebrospinal fluid or a positive
      culture for cryptococcal neoformans from the cerebrospinal fluid. RESULTS: Of 100
      patients enrolled in this study, 58 patients had cryptococcal meningitis and
      serum cryptococcal antigen was detectable in 60 patients. If the cut-off point
      for a positive test was when the serum cryptococcal antigen titer was more than
      zero, then, the sensitivity of the test was 91.4 per cent, the specificity was
      83.3 per cent, likelihood ratio if test positive (LR+) was 5.47, likelihood ratio
      if test negative (LR-) was 0.1, false positive was 16.7 per cent, false negative
      was 8.6 per cent. CONCLUSION: We conclude that serum cryptococcal antigen is a
      simple and rapid screening method for diagnosis of cryptococcal meningitis.

PMID- 10087742
TI  - Anterior stabilization in the pubic symphysis separation: a mechanical testing.
AB  - Four types of commonly used instruments, 1) external fixation, 2) tension wiring,
      3) tension band wiring, and 4) single superior plating, for anterior
      stabilization of the diastasis pubic symphysis were tested for their mechanical
      properties under single load to failure in cadaveric pelvis by a universal
      testing machine. Three directions of loading, transverse tension, vertical
      tension and saggital compression, were used to test each type of instrumentation.
      Five specimens of each fixation were used for each direction of testing. The
      strongest instrumentation was single superior plating. Early mobilization can be
      advocated in the patient after fixation with this instrument. External fixation
      could resist transverse and saggital compression load at an acceptable level but
      not the vertical load. Tension band wiring could better resist vertical load than
      the other directions. Tensions wiring was the weakest instrumentation and early
      ambulation should be avoided.

PMID- 10087743
TI  - Salivary antiepileptic drug levels in Thai children.
AB  - A total of 123 patients were enrolled in this study. 88 patients were enrolled in
      the first stage of the study, which was to evaluate the commercial salivary
      collecting devices: Orasure and Omnisol. 35 patients were enrolled in the second
      stage of the study and were asked to spit whole saliva samples for further
      analysis of AED levels. Serum AED levels and corresponding saliva AED levels were
      paired and analyzed for the correlation coefficients with the linear regression
      model. None of the commercial salivary collecting devices can provide the linear
      regression correlation between the serum AED level and saliva AED level in all
      three AEDs studied. The correlation coefficients of serum and whole saliva AED
      levels of phenobarbital, phenytoin, and carbamazepine were highly correlated (r
      squared were 0.981, 0.976, and 0.888, respectively). Saliva samples can be used
      clinically to monitor the AEDs level in phenobarbital, phenytoin and
      carbamazepine. This would be another alternative method of therapeutic drug
      monitoring that can be done painlessly and is easier in children than the blood
      sampling method.

PMID- 10087744
TI  - Hemophiliacs bone pseudotumors.
AB  - Four cases of proved hemophiliac pseudotumors caused by intraosseous bleeding are
      reported. Five lesions were found at the uncommon locations involving the cranial
      vault, mandible, phalanx, distal femur and distal tibia. The conventional
      radiographic and computed tomographic findings are expansile osteolytic
      destruction, cortical thinning, partial breaking cortex or pathological fracture,
      and sometimes associated soft tissue mass. Ultrasonographic feature of one case
      at the phalanx shows cortical expansion and thinning contained mixed echogenicity
      in the medullary canal with soft tissue extension. T99m DTPA of one case at the
      distal femur shows increased vascular flow and uptake at right distal tibia and
      left distal femur.

PMID- 10087746
TI  - Credibility of our profession. "Therefore trust the physician and drink his
      remedy in silence and tranquillity" Kahlil Gibran 1893-1931.

PMID- 10087745
TI  - Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome is an extremely rare condition of premature
      aging. It is characterized by growth retardation and accelerated degenerative
      changes of cutaneous, musculoskeletal and cardiovascular systems. The
      pathogenesis of the disease is unknown. The patients usually appear normal at
      birth. Typical manifestations develop gradually and are evident by the first or
      second year of life. They have a remarkably similar physical appearance
      consisting of short stature, alopecia, craniofacial disproportion, micrognathia,
      hypoplastic mandible, beak-like nose, decreased subcutaneous fat, atrophic skin,
      sclerodermoid lesion, mottling hyperpigmentation, prominent scalp veins,
      prominent eyes, protruding ears with absence of earlobes, faint midfacial
      cyanosis, delayed closure of fontanelles and sutures, delayed dentition, horse
      riding stance, thin limbs with prominent stiff joints, coxa valga, skeletal
      hypoplasia and dysplasia, dystrophic nails and high-pitched voice. Laboratory
      investigations are unremarkable. Metabolic, endocrine, serum lipid and
      immunologic studies show no uniform abnormalities. Typical radiographs
      demonstrate evidence of resorption of the distal ends of clavicles, attenuation
      of the terminal phalanges, diffuse osteopenia, and fishmouth vertebral bodies. In
      this report, a 3-year-old Thai girl with typical characteristics of Hutchinson
      Gilford progeria syndrome is described.

PMID- 10087747
TI  - Suicide and parasuicide in Pakistan: time for a change?

PMID- 10087748
TI  - Benzodiazepine self-poisoning in Pakistan: implications for prevention and harm
      reduction.
AB  - The pattern of all index admissions for benzodiazepine self-poisoning to a
      university hospital in Karachi, Pakistan are described. Of the 329 medication
      self-poisoning cases, 84% were benzodiazepine overdoses. Diazepam was the
      preferred drug in 69% of these cases, with majority ingesting between 20-30
      tablets of 5 mg each, 44% bought the benzodiazepine over the counter (OTC) for
      the purpose of overdose. The preference for benzodiazepines over analgesics (as
      freely available) may be related to the motives underlying parasuicide acts and
      their popularity as 'sleeping pills' in Pakistan. Educating the 'chemist' and
      limiting the number of tablets dispensed at a time are areas to consider in
      reducing the incidence and harmful effects of benzodiazepine overdoses in
      Pakistan.

PMID- 10087749
TI  - The pattern of benign gestational trophoblastic disease in Karachi.
AB  - A hospital based epidemiological study of benign gestational trophoblastic
      disease i.e., both complete and partial hydatidiform mole was undertaken at 8
      hospitals. The frequency of the disease was found to be 3.89/1000 pregnancies and
      was found to be higher--1 in 237 deliveries in the economically deprived women
      admitted to a free Government Hospital, compared to only 1 in 471 deliveries in a
      Private, fee-for-service hospital. Risk factors identified, were: age above 35
      years (OR = 7.39, CL 5.54-9.87); or under 20 years (OR = 2.14, CL = 1.60-2.85),
      history of previous molar pregnancy (OR = 18.44, CL = 49.4-74.09), past history
      of abortions (OR = 1.96, CL = 1.49-2.57) and recurrent abortions (OR = 3.26, CL =
      1.82-5.77). Blood group A was also found to be a significant risk factor (OR =
      1.6, CL = 1.01-2.53). Progression to gestational trophoblastic tumor was found in
      3% patients with hydatidiform mole. A plea is made for earlier diagnosis at
      asymptomatic stage, to reduce morbidity; histopathological examination of all
      abortuses will help identify complete and partial moles which would otherwise be
      overlooked. Finally, improvement in follow-up system and establishment of a data
      base is recommended.

PMID- 10087750
TI  - Treatment of pemphigus: a local experience.
AB  - A clinical study was conducted to evaluate the efficacy and safety of three
      currently used treatment modalities for pemphigus. Seventy-two patients of
      pemphigus (pemphigus vulgaris and severe cases of pemphigus vegetans, pemphigus
      foliaceous and pemphigus erythematosus) were divided into three groups. Forty
      patients were treated with prednisolone, 15 with a combination of prednisolone
      plus azathioprine and 17 patients with betamethasone-cyclophosphamide pulse (BCP)
      therapy. All patients were followed from 9 to 21 months (mean 16 months). There
      was no statistical difference between steroid and azathioprine-corticosteroid
      therapy groups in terms of time taken to achieve initial control of the disease
      but the frequency of relapses and the incidence of complications were higher in
      patients treated with corticosteroids alone (p < 0.05). A marginally increased
      susceptibility to infections was seen in patients treated with BCP therapy as
      compared with azathioprine-corticosteroid group (p = 0.07). Seventy percent
      patients treated with BCP therapy required additional steroids in between the
      monthly pulses, indicating failure of BCP as sole therapy. It was concluded that
      azathioprine-corticosteroid treatment of pemphigus was more effective and
      comparatively safer than steroid alone or BCP therapy.

PMID- 10087751
TI  - Cutaneous manifestations of diabetes mellitus.
AB  - Of 100 cases of diabetes mellitus examined for cutaneous findings 82% showed
      cutaneous lesions. Infection (49%) was the most common finding followed by
      involvement of foot (30%). High incidence of vitiligo (10%) and localized
      anogenital pruritus (19%) was an unusual feature. Some of the cutaneous markers
      of diabetes mellitus like necrobiosis lipoidica diabeticorum, diabetic bullae,
      acquired perforating dermatoses and scleredema were not seen in this study.

PMID- 10087752
TI  - Snake bite in the Thar Desert.
AB  - Snake bite remains a common injury in endemic areas of Pakistan. A facility based
      observational study was undertaken to ascertain the incidence of snake bite, its
      mortality and the management in public health facilities located in the Thar
      Desert of Province of Sindh, Pakistan. A total of 771 cases of snake bite were
      reported to seven randomly selected health facilities during a one-year period.
      Most (75%) occurred during nighttime in summer, affecting primarily males (70%)
      who were bitten mostly on the lower extremities (83%). Five hundred and thirteen
      bites (66%) were identified as poisonous and 4 deaths were reported. Seventy two
      percent of patients reached the health facility within 24 hours and twenty
      percent within 6 hours and of being bitten. Snake bite remains an important
      problem in endemic areas of Pakistan. People do seek assistance at public health
      facilities, where appropriate treatment including anti snake venom is given.

PMID- 10087753
TI  - Snake bite experience at Pakistan Institute of Medical Sciences.
AB  - We reviewed 40 cases of snake bite seen from January, 1996 to December, 1996.
      Most of the cases survived uneventfully but many developed complications which
      were either haematologic, (23 patients) or neurological (5 patients). Appropriate
      treatment was offered in every case. Polyvalent antisnake venom was administered
      to 30 patients (75%). Premedication used was steroids and antihistamines to
      prevent anaphylactic reactions. Antifibrinolytic therapy (tranxemic acid) was
      given to every bleeding patient. The species of offending snake could be
      recognized in one patient while in all others, it was not possible due to night
      time incidence and poor description by the patient.

PMID- 10087754
TI  - Role of fibreoptic bronchoscopy in the management of immunocompromised patients
      with pulmonary infiltrates.
AB  - Immunocompromised patients are prone to develop various pulmonary complications.
      The range of diagnostic possibilities is wide, infection being the commonest
      cause. Non-invasive diagnostic tests are often unrewarding. In this study, we
      have evaluated the diagnostic efficacy and safety of fibreoptic bronchoscopy in
      immunocompromised patients with pulmonary infiltrates. Patients tolerated the
      procedure well. This technique identified the etiology in up tp 75% of cases.
      After treatment based on the result of bronchoscopy, 63% patients improved and
      were discharged.

PMID- 10087755
TI  - Two years' study of pattern and frequency of fatal injuries.

PMID- 10087756
TI  - Presentation and management of talon cusp.

PMID- 10087757
TI  - Fixed drug eruption with albendazole and it's cross-sensitivity with
      metronidazole--a case report.

PMID- 10087758
TI  - From Yac-1, back to square one.

PMID- 10087759
TI  - [Present status and progress of endocrine nuclear medicine].
AB  - The author reviewed present status and progress of endocrine nuclear medicine
      including thyroid, parathyroid, adrenocortical, adrenomedullary and somatostatin
      receptor imaging and also radionuclide therapy of Basedow's disease, metastatic
      foci of post-operative thyroid cancer and malignant neural crest tumor.
      Relatively new imaging agents include 99mTc-MIBI and 99mTc-tetrofosmin for
      parathyroid imaging and 111In-pentetreotide for somatostatin receptor imaging. It
      is hoped that therapy of malignant neural crest tumors such as metastatic
      pheochromocytoma and neuroblastoma with 131I-MIBG and somatostatin receptor
      imaging will be available in Japan as soon as possible.

PMID- 10087760
TI  - [Nuclear medicine of bone].
AB  - Bone scintigraphy using 99mTc-labeled phosphorous compounds was found to be the
      most frequently ordered nuclear medicine examination in a nationwide survey in
      Japan, and has been used for the detection of lesions and the evaluation of
      disease progression and response to therapy in various skeletal diseases. In this
      article, we review improvement of the diagnostic sensitivity and specificity for
      bone metastasis of not only nuclear medicine techniques, such as planar imaging,
      SPECT, early flow phase imaging and quantification of bone scintigraphy, and bone
      marrow scintigraphy but also such recently developed methods as bone mineral
      measurement, and bone metabolic marker assays. In addition, radionuclide therapy
      of intractable bone pain due to bone metastasis is also addressed.

PMID- 10087761
TI  - [Evaluation of 99mTc-MAG3 (mercaptoacetyltriglycine) renography for pediatric
      patients].
AB  - It is difficult to evaluate renal function with 99mTc-MAG3 renography in both
      adult and pediatric patients. We examined 109 pediatric patients with various
      renal diseases using 99mTc-MAG3 renography. Tenal diseases were classified as
      follows: 9 vesicoureteral reflux, 4 ureteropelvic junctional stenosis, 3 double
      pelvis, 23 hydronephrosis, 4 glomerulonephritis, 4 nephrotic syndrome, 24
      hemolytic uremic syndrome, 10 others; and 24 patients without abnormal findings
      on other examinations. After hydration and sedation, 100-200 MBq of 99mTe-MAG3
      was injected intravenously. All patients were placed in the supine position, and
      dynamic data acquisition at 12 sec/frame x 100 frames was performed from the
      back. The renograms were prepared with the ROIs (regions of interest) set to
      include the entire kidney. Tmax and T1/2 of renograms were measured for 26
      kidneys with no abnormal findings. The correlations between Tmax or T1/2 and age
      (days after birth) were determined by a linear or logarithmic function. The
      logarithmic function (Y = 7.49 - 0.56 logeX, r2 = 0.134) yielded a higher
      correlation than did the linear function (Y = 5.16 - 0.00194X, r2 = 0.089)
      between Tmax and age. For T1/2 and age (days after birth), the linear function (Y
      = 8.07 - 0.00451X, r2 = 0.222) yielded a higher correlation than the logarithmic
      function (Y = 11.9 - 0.986 logeX, r2 = 0.192). Our findings suggest that
      prolonged Tmax is normalized more rapidly than T1/2 after birth in infants. A
      delayed excretion phase is not suggestive of renal dysfunction, but is
      characteristic of renograms in pediatric patients. Abnormality was detected in
      all patients with hydronephrosis using 99mTc-MAG3 renography. On the other hand,
      a quantitative study was required because renography detected no abnormality for
      some of patients with disorders of renal parenchyma.

PMID- 10087762
TI  - [Assessment of left ventricular function by 201Tl ECG-gated myocardial SPECT].
AB  - We applied the QGS program for LV function analysis (described by Germano, 1995)
      to a 201Tl SPECT study at rest, and estimated its accuracy. We performed 201Tl
      ECG-gated myocardial SPECT in 25 patients with ischemic heart disease under an
      acquisition time used in the routine 99mTc ECG-gated SPECT study. The quality of
      the gated images was visually assessed with a 4-point grading system. LVEDV,
      LVESV, LVEF determined by the QGS program were compared with those by Simpson's
      method on biplane LVG in 25 patients. Regional wall motion scores in 7 myocardial
      segments were assessed on the three-dimensional display created by the QGS
      program and the cine display of biplane LVG with a 5-point grading system. Wall
      motion scores obtained by the QGS program were compared with those by LVG.
      Although 72.0% of 201Tl ECG-gated SPECT images were fair or poor in image
      quality, there were good correlations between the values obtained by the QGS
      program and LVG (LVEDV: r = 0.82, LVESV: r = 0.88, LVEF: r = 0.89). In addition,
      wall motion scores by the QGS program were correspondent to those by LVG in 77.1%
      of all 175 myocardial segments. We conclude that the QGS program provides high
      accuracy in evaluating left ventricular function even from 201Tl ECG-gated
      myocardial SPECT data.

PMID- 10087763
TI  - [99mTc-DTPA-HSA lymphoscintigraphy in lymphedema of the lower extremities:
      diagnostic significance of dynamic study and muscular exercise].
AB  - The efficacy of lymphoscintigraphy was evaluated in 25 cases to clarify the
      diagnostic significance of dynamic study and muscular exercise in the diagnosis
      of lymphedema. 99mTc-diethylene triamine pentaacetic acid-human serum albumin
      (DTPA-HSA) was injected subcutaneously, and dynamic imaging was performed in 18
      cases. Thirteen patients were asked to walk for 3 minutes. Qualitative evaluation
      of static images had sensitivity of 90% and specificity of 97%. Diagnostic
      criteria including qualitative evaluation of dynamic images were less specific
      (sensitivity 95%, specificity 76%). Interpretation of static images obtained at
      one hour after injection in the patients without muscular exercise had
      sensitivity of 89% and specificity of 67%, whereas sensitivity was 92% and
      specificity was 100% in the patients with muscular exercise. Lympho-scintigraphy
      was reliable in diagnosis of lymphedema. Dynamic study was limited usefulness
      because of some false-positive cases. Muscular exercise accelerated migration of
      the tracer in normal extremities, and improved positive predictive value.

PMID- 10087764
TI  - [Evaluation of the liver uptake rate measured by 99mTc-GSA SPECT to assess liver
      function].
AB  - Whether the global liver uptake rate of 99mTc-GSA directly measured by SPECT is
      useful as a new index of liver function was evaluated in comparison with
      biochemical test results (PT%, ChE, Alb, ICG R15, KICG) and Child classification.
      99mTc-GSA SPECT was performed in 157 patients with diffuse hepatic disease or
      hepatobiliary tumor, and two indices, namely the global liver uptake rate
      measured by SPECT 15 minutes after intravenous injection of 99mTc-GSA (LUS 15)
      and liver uptake per volume (liver uptake density) were examined. Both LUS 15 and
      liver uptake density were significantly correlated with biochemical test results
      and Child classification. In particular, close relationships between LUS 15 and
      ICGR15 (r = -0.720, p < 0.0001), LUS 15 and KICG (r = -0.750, p < 0.0001), and
      between LUS 15 and ChE (r = 0.720, p < 0.0001), indicate that LUS 15 is a useful
      index to evaluate liver function. Moreover, the local liver uptake rate measured
      by SPECT represented regional liver function and was considered a useful index to
      predict the function of the remnant liver after invasive treatment such as
      surgery.

PMID- 10087765
TI  - [The usefulness of 123I-BMIPP myocardial SPECT in diagnosis for silent myocardial
      ischemia induced by vasospasm].
AB  - This study was designed to evaluate the clinical usefulness of 123I-BMIPP
      myocardial SPECT in patients with silent myocardial ischemia induced by
      vasospasm. Ultrasonic echocardiography (UCG), Holter electrocardiogram recording
      (Holter ECG), exercise 201Tl myocardial SPECT (EX-Tl) and rest 123I-BMIPP
      myocardial SPECT (BMIPP) were performed in 8 patients with asymptomatic vasospasm
      without history of myocardial infarction. The sensitivity of each modality in
      detecting coronary artery spasm was 37.5% (3 of 8 cases) for UCG, 37.5% (3 of 8
      cases) in Holter ECG, 25.0% (2 of 8 cases) in Ex-Tl, 62.5% (5 of 8 cases) on
      initial BMIPP images and 75.0% (6 of 8 cases) on delayed BMIPP images. Severity
      of regional left ventricular wall motion abnormality in UCG correlated with the
      severity of regionally decreased tracer uptake in BMIPP. The washout rate of
      BMIPP was 18.7 +/- 2.4 in normal controls, 32.4 +/- 5.9 in asymptomatic
      vasospasm, and 38.2 +/- 4.0 in asymptomatic vasospasm with abnormal left
      ventricular wall motion. It was suggested that 123I-BMIPP myocardial SPECT might
      be useful for assessing asymptomatic vasospasm.

PMID- 10087766
TI  - [Measurement of cerebral blood flow the blood sampling method using 99mTc-ECD:
      simultaneous scintigram scanning of arterial blood samples and the brain with a
      gamma camera].
AB  - To measure regional cerebral blood flow (rCBF) by blood sampling using 99mTc-ECD
      we devised a method of measuring the radioactive concentration in arterial blood
      sample with a gamma camera. In this method the head and a blood sample are placed
      within the same visual field to record the SPECT data of both specimens
      simultaneously. The results of an evaluation of the counting rate performance,
      applying the 30 hours decaying method using 99mTc solution showed that this
      method is not comparable to the well-type scintillation counter and in clinical
      cases the active concentration in arterial blood sample remained well within the
      dynamic range. In addition, examination of the influence of scattered radiation
      from the brain by the dilution method showed that it was negligible at a distance
      of more than 7.5 cm between the brain and the arterial blood sample. In the
      present study we placed a head-shaped phantom next to the sample. The results of
      the examinations suggested that this method is suitable for clinical application,
      and because it does not require a well-type scintillation counter, it is expected
      to find wide application.

PMID- 10087767
TI  - [A SBU study of indications for interventions in coronary arteries can be
      questioned. Debatable methods give misleading results].

PMID- 10087768
TI  - [Physicians' responsibility in the health care crisis].

PMID- 10087770
TI  - [Suitability as head physician requires more than medical education].

PMID- 10087769
TI  - [The development of andrology must have a scientific basis].

PMID- 10087772
TI  - [Incorrect marketing].

PMID- 10087771
TI  - [Risk of wrong analytic results in specimen collection from subcutaneous
      injection port].

PMID- 10087773
TI  - [Goya's "Diphtheria" in reality was an eaten sausage].

PMID- 10087774
TI  - [Promising experiments with DNA vaccine against HIV. A complete eradication of
      the virus is a formidable task].
AB  - The past few years have witnessed encouraging progress in experimental HIV
      vaccination. Several new vaccine candidates have been shown to elicit immune
      response and provide protection in animals, and the first immunotherapy trials in
      humans have been reported. Difficulties remain to be overcome, however. No
      consensus exists regarding trials in humans. Some researchers and clinicians
      believe that we must await a vaccine demonstrably and reproducibly effective in
      animals. Immunogenicity alone is considered insufficient to ensure clinical
      protection. Others consider animal experiments valuable, but believe that actual
      trials should be made in humans in the target population. Trials are urgently
      needed in countries with high transmission rates, even if optimal efficacy cannot
      be guaranteed.

PMID- 10087775
TI  - [Clinical assessment of critical ischemia is always to be done prior to
      amputation].
AB  - Patients with critical limb ischemia (rest pain and/or ulcer/gangrene, together
      with low ankle pressure) are at risk of amputation, and should therefore undergo
      arterial reconstruction if that is at all technically possible. Thorough clinical
      investigation will usually distinguish patients in need of further evaluation by
      a vascular surgeon. No amputation should be undertaken without such evaluation.
      Diabetic patients belong to a special category, in that neuropathy makes it
      difficult to evaluate pain, and ankle pressure is often falsely high due to
      medial arterios sclerosis.

PMID- 10087776
TI  - [Indications for coronary vessel interventions - 1. Swedish application of an
      American model is scrutinized].

PMID- 10087777
TI  - [Indications for interventions in coronary vessels - 2. Patients' perception in
      focus for the assessment].

PMID- 10087778
TI  - [Hallucinogenic mushrooms popular again--sale via Internet].

PMID- 10087779
TI  - [Medical aspects of diving--a sport for both women and men].
AB  - As interest in scuba diving is increasing in both sexes, doctors need to be aware
      of the risks encountered when diving and about gender-related differences in
      these risks. Individuals prone to panic attacks, claustrophobia or reckless risk
      taking should avoid diving. In tolerating cold, muscle mass is more important
      than the amount of subcutaneous fat. The risk of decompression disease seems to
      be slightly greater among women, probably due to their fat distribution. Pregnant
      women are recommended not to dive, because the risk of birth defects seems to be
      greater among those who do, and there is a serious risk of fetal decompression
      disease. All participants in the sport must be responsible for their own diving
      safety.

PMID- 10087780
TI  - [A course in gynecology makes the gender perspective more obvious].

PMID- 10087781
TI  - [SBU Alert evaluates new medical technology. A tool on the net will update the
      health care administrators responsible for decisions].

PMID- 10087782
TI  - [Thrombolysis in stroke. An evaluation by the SBU Alert].

PMID- 10087783
TI  - [Most of the women with early miscarriage do not need curettage].

PMID- 10087784
TI  - [Unsolicited medical interventions cause ethical conflicts. This is the opinion
      of physicians, medical students and the public in Europe].

PMID- 10087785
TI  - [Asthma inhaler ejected a foreign body into the airways].

PMID- 10087786
TI  - [High price for cheap powdered gloves].

PMID- 10087787
TI  - ["Clinicians must evaluate Internet". A top-list made by a group of general
      practitioners].

PMID- 10087788
TI  - [Have we lost the battle against antibiotic resistance? Irreversible damage to
      the microbial environment may be seen already].

PMID- 10087789
TI  - [Multidisciplinary medical ethics].

PMID- 10087790
TI  - [Increased equality of health is the aim of Infomedica].

PMID- 10087791
TI  - [The concept of natural science must be elucidated].

PMID- 10087792
TI  - [We don't want to rub the New Age philosophies the right way--on the contrary!].

PMID- 10087793
TI  - [Better knowledge of transcultural psychiatry and migration medicine is
      required].

PMID- 10087794
TI  - [Management of errors by the National Board of Health and Welfare seem to be
      directed against the law on quality of health care].

PMID- 10087795
TI  - [Down's or Down syndrome?].

PMID- 10087796
TI  - [Development of resistant Helicobacter pylori in Sweden. Tendency toward
      increasing resistance to clarithromycin].
AB  - This study was designed to investigate the development of antibiotic resistance
      in Swedish H pylori isolated 1990-96. A total of 415 isolates collected from 10
      clinical microbiology laboratories were examined. Three different methods of
      susceptibility testing were compared: agar dilution, the E-test and disc
      diffusion. None of the isolates was resistant to ampicillin or tetracycline, but
      approximately 30 per cent were resistant to metronidazole. An increase in
      resistance to clarithromycin was noted during 1996 (9% resistant strains), though
      the significance of this finding needs further investigation. The comparison of
      susceptibility tests suggested disc diffusion to be of doubtful value, but the E
      test to be appropriate for testing H pylori. However, the number of isolates
      resistant to metronidazole was higher with the E-test than with agar dilution.
      The value of testing susceptibility to metronidazole is discussed.

PMID- 10087797
TI  - [30 years of successful mycobacteriology research, The AHRI in Addis Abeba--a
      unique research environment in a developing country].
AB  - The Armauer Hansen Research Institute (AHRI) in Addis Abeba, Ethiopia, was
      established by the Swedish and Norwegian Save the Children organisations in
      collaboration with the University of Bergen, with the principal objective of
      pursuing basic research in leprosy. The institute has a commendable record of
      achievement, and has made significant contributions to our understanding of
      leprosy and its control, and to the training of scientists from Ethiopia and
      other African countries. Recently, the Ethiopian, Swedish and Norwegian
      governments agreed to continue supporting the AHRI as an autonomous research
      centre. Its main objectives will be to conduct research in mycobacterial
      diseases, particularly tuberculosis, and to promote the enhancement of human
      resources in health research through instruction, supervision, and scientific
      collaboration.

PMID- 10087798
TI  - [Free from stress by autogenic therapy. Relaxation technique yielding peace of
      mind and self-insight].
AB  - The utilisation of self-regulatory capacity is one of the purposes of autogenic
      therapy, a method consisting of exercises focused on the limbs, lungs, heart,
      diaphragm and head. The physiological response is muscle relaxation, increased
      peripheral blood flow, lower heart rate and blood pressure, slower and deeper
      breathing, and reduced oxygen consumption. Autogenic training is applicable in
      most pathological conditions associated with stress, and can be used preventively
      or as a complement to conventional treatment.

PMID- 10087799
TI  - [Laparoscopy in acute abdomen as diagnostic and surgical aid].
AB  - In cases of acute abdomen, the preoperative diagnostic options are limited.
      Diagnostic laparoscopy offers a superior overview of the abdominal cavity with
      minimal trauma to the patient. If further surgery is needed, it may take the form
      of either laparoscopic procedures or conversion to open surgery, the incision
      being guided by laparoscopy findings. Complications associated to laparoscopy are
      few and can be minimized further by using minilaparotomy techniques. Intensive
      educational programmes for all categories of staff are required to make a 24
      hours-a-day laparoscopy service available.

PMID- 10087800
TI  - [The museum of medical history in Linkoping welcomes visitors. Exciting and
      "sensual" experiences are waiting].

PMID- 10087801
TI  - [Jimmie, the bulldog, was a patient assistant at the first ECG registration].

PMID- 10087802
TI  - [Are all diseases infectious? New findings on bacteria in relation to kidney
      stones].

PMID- 10087803
TI  - [Three cases of abdominal pregnancy. A condition difficult to diagnose even with
      modern equipment].

PMID- 10087804
TI  - [To make right things or to make things right? Difficult balancing of clinical
      audit of psychiatric care].

PMID- 10087805
TI  - [Why was primary computer tomography not performed?].

PMID- 10087806
TI  - [Normal findings by computer tomography do not exclude CNS injury].

PMID- 10087807
TI  - [Infertile men, wherever they live, should have a chance to become genetic
      fathers].

PMID- 10087808
TI  - [Prevention--illusion or hope for the future?].

PMID- 10087809
TI  - [The care of diabetes can be assured by the DRP (Diabetes Responsible
      Physicians)].

PMID- 10087810
TI  - [A study of Creutzfeldt-Jakob disease during 1985-96. No indication of cases of
      the "mad cow disease" in Sweden].
AB  - A retrospective study of Creutzfeldt-Jakob disease (CJD) in Sweden during the
      period 1985-96 yielded an annual incidence of 1.18 per million. Data for
      incidence, age distribution (at onset and at death), and duration of illness were
      similar to those of other countries, with the exception of new variant CJD
      (nvCJD) cases in the UK, and as far as can be judged the symptomatology was also
      similar. So far, there is no indication of the occurrence of any cases of nvCJD
      in Sweden.

PMID- 10087811
TI  - [Bodily evidence can reveal torture. 5-year experience of torture documentation].
AB  - At the Centre for Torture and Trauma Survivors in Stockholm, 201 subjects from 34
      countries were documented during a period of five years. Torture reports differed
      little between individuals from the same countries or regions, regarding methods
      and circumstances. Africans from Uganda (n = 22) reported brutal torture and
      manifested extensive scarring (mean number of scars, 20; range 4-65), whereas
      subjects from Syria (n = 28) reported falaka (i.e., bastinade), whipping and
      suspension, but manifested few or no scars (mean number 5, range 0-17). Of the
      subjects examined, 17% were women, of whom 79% reported having been raped during
      torture. Chronic back pain was the most common complaint at the time of
      examination. Correlation was found to exist between sexual torture and genito
      urinary symptoms, bastinade and neural symptoms, and electrical torture and
      symptoms from the joints and gastro-intestinal tract. Severity of physical
      torture was a correlate of post-traumatic stress disorder. However, the forensic
      report had no effect on the verdict of immigration authorities regarding
      individual asylum applications.

PMID- 10087812
TI  - ["Torture has become an epidemic": Turkish physicians organize to help their
      countrymen].

PMID- 10087813
TI  - [How could Linne be so wrong when it comes to malaria? Yesterday's knowledge is
      not always correct--but neither is today's].

PMID- 10087814
TI  - [Increasing infant mortality and tuberculosis in China. A dark picture of public
      health and health care in China].

PMID- 10087815
TI  - [The new debate on cholesterol: is the lowest level the best?].

PMID- 10087816
TI  - [Expressive sound language. Reflections on music and psychosocial medicine].

PMID- 10087817
TI  - [Correlation between intraoperative hemodynamic variability and postoperative
      arrhythmias in patients with pulmonary surgery].
AB  - Multivariate analyses were performed by logistic regression procedure to identify
      the significant risk factors for postoperative arrhythmias. The 29 variables
      included in the analyses were as follows: age, sex, hemodynamic variability,
      preoperative complication (hypertension, myocardial ischemia, and diabetes
      mellitus et al), surgical staging for lung cancer, anesthetic method, surgical
      procedure, intraoperative complications (hypoxemia, arrhythmia and myocardial
      ischemia), and so on. We evaluated intraoperative hemodynamic variability using
      mean value and coefficient of variation (CV) of heart rate and blood pressure
      computed from anesthetic records. Supraventricular tachyarrhythmias occurred in
      27 (22.3%) of 121 consecutive patients undergoing pulmonary resection. Increases
      in mean heart rate and CV of heart rate, older patients, intraoperative blood
      transfusion, and left thoracotomy were associated with arrhythmias (P < 0.05).
      There was no correlation of arrhythmia with preoperative complications, surgical
      staging for lung cancer, anesthetic method, or surgical procedure. It is
      suggested that impairment of cardiac autonomic nervous system function associated
      with possible injury to the cardiac autonomic nerves during pulmonary resection
      is one of the risk factors for arrhythmias after thoracotomy.

PMID- 10087818
TI  - [Continuous total intravenous anesthesia is useful for postoperative pain
      management].
AB  - We compared postoperative pain in two groups. All anesthetic agents were
      continuously administered intravenously in a continuous PKF (propofol 2-10 mg.kg
      1.h-1, ketamine 240 micrograms.kg-1.h-1 and fentanyl 0.4 microgram.kg-1.h-1)
      group. In a control group, anesthesia was maintained by GOI (N2O-oxygen
      isoflurane). Twenty-two patients scheduled for gynecological lower abdominal
      surgeries were divided into the continuous PKF group (n = 11) and the GOI group
      (n = 11). Epidural anesthesia was employed in both groups, using local anesthetic
      agents and fentanyl during surgeries and for 24 hrs postoperatively. To evaluate
      pain, VAS and Prince Henry Score on rest, cough and movement were taken 2 hrs and
      5 hrs postoperatively, and in the morning and afternoon of the 1st as well as 2nd
      postoperative days. The continuous PKF group showed lower scores than the GOI
      group. It is a great advantage to use continuous PKF for postoperative pain
      management, and our data indicate that low dose ketamine may induce pre-emptive
      analgesia.

PMID- 10087819
TI  - [Influences of chest deformation by upper abdominal retractor on respiratory
      system impedance during abdominal surgery].
AB  - The present study was carried out to clarify the effects of chest deformation by
      upper abdominal retractor on respiratory system impedance during abdominal
      surgery. We measured the impedances of respiratory system (RS), lung, and chest
      wall (CW) in nine anesthetized paralyzed subjects employing a pseudorandom noise
      forced volume oscillation technique. These measurements were performed before and
      after the lifting chest wall by upper abdominal retractor. The effects of chest
      deformation was significant on the impedances of RS, lung, while no discernible
      effect was found in CW impedance. Lifting chest wall decreased RS resistance
      which was totally accounted for by the decrease in lung resistance, whereas the
      lifting did not affect reactance in either RS or lung. The mathematical modeling
      showed the significant lifting effect on the resistance of the parenchyma. In
      conclusion, change in RS mechanics produced by chest deformation by upper
      abdominal retractor is dominated in lung but not in CW. Among the lung mechanical
      components, parenchyma is the primary site of the lifting effect.

PMID- 10087820
TI  - [Changes in ionized magnesium concentrations during general anesthesia].
AB  - The change in ionized magnesium (Mg) was investigated during isoflurane-nitrous
      oxide-oxygen anesthesia. The patients were divided into two groups by induction
      method of anesthesia. Group 1 was induced with thiamylal 4 mg.kg-1 and Group 2
      was induced with ketamine 1 mg.kg-1. The ionized Mg concentration was recorded by
      NOVA 8 analyzer and observed during anesthesia. We also recorded the serum
      concentration of total Mg after administration of thiamylal. During induction of
      anesthesia and surgery, ionized Mg concentration decreased significantly in both
      groups. The ionized Mg concentration after administration of thiamylal was
      significantly lower than that after administration of ketamine. The serum total
      Mg concentration did not decrease throughout the anesthesia course. The ionized
      calcium concentration decreased, but the concentration of Na and K remained
      essentially unchanged. We conclude, therefore, that ionized Mg concentration
      decreases during surgery under general anesthesia, in part, possibly by the
      effect of anesthetic agent on the cell membrane itself.

PMID- 10087821
TI  - [Prolonged antinociceptive effect of poly (DL-lactic acid)-fentanyl composites
      after their intrathecal injection in rats].
AB  - We synthesized poly (DL-lactic acid)-fentanyl composites and compared the
      duration of analgesia after the administration of a single intrathecal dose of
      these agents in rats. The drug was injected with an intrathecal catheter into the
      intrathecal space. Fentanyl composites or plain fentanyl in doses of 2.5 or 25
      micrograms were administered, respectively. Animals were then tested for
      analgesia using the tail-flick test. The release rate of fentanyl from fentanyl
      composites in vitro was also evaluated. The antinociceptive effect of fentanyl
      composites (25 micrograms) was significantly longer than that of plain fentanyl.
      Administration of poly (DL-lactic acid) alone did not induce the antinociceptive
      effect. Four of 7 animals given plain fentanyl (25 micrograms) exhibited
      temporary respiratory depression, but none of the animals given fentanyl
      composites showed this response. In vitro experiments demonstrated a slow release
      of fentanyl from the fentanyl composites. We conclude that the antinociceptive
      effect of fentanyl can be prolonged when administered as a poly (DL-lactic acid)
      fentanyl composite in the intrathecal space with decreased systemic side effects
      compared with the plain formulation.

PMID- 10087822
TI  - [Current topics in the regulation of prostanoids--4. The feedback regulation by
      PPAR-gamma].
AB  - Recently, it has become known that lipophilic hormones such as steroids and
      thyroid hormones, or fat-soluble vitamins (vitamins A and D) pass through the
      cellular membrane and bind to the nuclear receptor superfamily to act as
      transcription factors. The metabolite of prostaglandin (PG) D2, 15-deoxy
      D12,14PGJ2, has been identified as the ligand for peroxisome proliferator
      activated receptor gamma (PPAR-gamma), a member of the nuclear receptor
      superfamily. It forms a transcription factor and is responsible not only for the
      differentiation of fibroblasts to adipocytes, but also for the regulation of
      activated macrophages. It is now known that thiazolidinediones and non-steroidal
      anti-inflammatory drugs classified as cyclooxygenase blockers such as
      indomethacine and ibuprofen also act as PPAR-gamma agonists and inhibit cytokine
      production from activated macrophages. PPAR-gamma has become recognized as a new
      therapeutic target for inflammation control.

PMID- 10087823
TI  - [Anesthetic management for pericardial fenestration in a hypertrophic
      cardiomyopathy (HCM) patient with massive pericardial effusion].
AB  - A 65 year-old male with HCM had progressively increased pericardial effusion. He
      also had atrial fibrillation (af), cardiac systolic dysfunction and chronic renal
      failure needing hemofiltration. Pericardial fenestration was carried out to
      improve diastolic function. Anesthetic management with fentanyl plus low-dose
      propofol infusion and postoperative analgesia with epidural morphine were
      effective for hemodynamic stability to prevent myocardial depression and to
      control ventricular response to atrial fibrillation. Intraoperative trans
      esophageal echocardiography (TEE) monitoring was very useful for fluid therapy,
      inotropic support and estimation of systolic and diastolic function.

PMID- 10087824
TI  - [Cesarean section in a patient with severe diabetic ketoacidosis associated with
      intracranial hemorrhage of the fetus].
AB  - A patient at 33 weeks of pregnancy with diabetic ketoacidosis was transferred to
      our hospital. Despite intensive medical treatment, fetal state deteriorated and
      fetal distress was documented. A decision was made to deliver the fetus
      immediately. An asphyxial neonate was delivered by cesarean section under spinal
      anesthesia. The neonate was resuscitated in the operating room and intensively
      managed at the pediatric ward. CT scan revealed the multiple intracranial
      hemorrhage in the neonate on the fifth day of the birth. Stringent glucose
      control during pregnancy is crucial for the health of both the mother and fetus.

PMID- 10087825
TI  - [General anesthesia with propofol and fentanyl for adult cardiac surgery].
AB  - We employed propofol anesthesia with a restricted dose of fentanyl in adult
      cardiac surgery with the aim of early tracheal extubation and evaluated its
      effects on the intraoperative factors and postoperative recovery compared with
      those of a previous benzodiazepine-fentanyl regimen. During surgery, control
      group patients (n = 17) received intermittent bolus of benzodiazepines and
      fentanyl without restriction, whereas propofol group patients (n = 17) received
      continuous administration of propofol and the restricted dose of fentanyl (20
      micrograms.kg-1). There were no significant differences in the times to eye
      opening (average 2.4 hr vs 1.6 hr, respectively, P = 0.30) and tracheal
      extubation (average 5.4 hr vs 4.0 hr, P = 0.25) between the groups. Both groups
      had similar postanesthetic circulatory status: cardiac index (average 3.6 l.min
      1.m-2 vs 3.4 l.min-1.m-2, P = 0.46). The propofol group patients required smaller
      doses of vasodilators during cardiopulmonary bypass (average PGE1: 0.096
      microgram.kg-1.min-1 vs 0.047 microgram.kg-1.min-1, P = 0.046, NTG: 0.69
      microgram.kg-1.min-1 vs 0.31 microgram.kg-1.min-1, P = 0.009). It is suggested
      that propofol-based anesthesia could replace the previous regimen with no adverse
      hemodynamic effects and might have a potential to provide faster recovery and
      improve peripheral circulatory status in adult cardiac surgery.

PMID- 10087826
TI  - [Arterial oxygenation during one lung ventilation in obese patients].
AB  - To test the hypothesis that arterial oxygenation during one lung ventilation
      (OLV) is impaired more in obese patients than in non-obese control patients, we
      performed consecutive measurements of arterial oxygen tension (PaO2) during OLV
      in 48 patients scheduled for pulmonary lobectomy. Minimum value of PaO2 during
      OLV was significantly less in 16 obese patients [body mass index (BMI) > 25]
      compared to 32 control patients (BMI < 25). Moreover, PaO2 value of left lung
      ventilation was significantly less than the value of right lung ventilation in
      obese patients while the difference was not statistically significant in the
      control group.

PMID- 10087827
TI  - [The blood sugar levels after hypothermic cardiopulmonary bypass in diabetic
      patients: their relation to preoperative values of hemoglobin-A1c and
      medication].
AB  - We studied the blood sugar levels after hypothermic cardiopulmonary bypass (CPB)
      in diabetics and non-diabetics. Twenty eight patients were divided to the
      following four groups by the preoperative value of hemoglobin-A1c (HbA1c) and
      medication; (1) HbA1c < 6.0 and given oral anti-diabetic medication, (2) HbA1c >
      6.0 and given oral anti-diabetic medication, (3) HbA1c > 6.0 and given insulin
      injection, and (4) non-diabetics. Both in diabetics and non-diabetics, the blood
      sugar levels were higher than 300 mg.dl-1 during cardiopulmonary bypass. In group
      (1) and (4), the blood sugar levels went down lower than 250 mg.dl-1 at 60
      minutes after CPB, without any treatment. In group (2) and (3), the blood sugar
      levels after 60 minutes of CPB were higher than 250 mg.dl-1, and insulin 8 units
      were given. After 30 minutes of insulin injection, the blood sugar levels of
      group (2) were lower than 250 mg.dl-1, but those in group (3), the blood sugar
      levels were still higher than 250 mg.dl-1, and another 8 units of insulin were
      given. The diabetic patients whose HbA1c levels were higher than 6.0 and given
      anti-diabetic medication before operation, need insulin after CPB.

PMID- 10087828
TI  - [Persistent neurological deficit and adhesive arachnoiditis following spinal
      anesthesia with bupivacaine containing preservatives].
AB  - A 75 year-old female with osteoarthritis of bilateral knee joints was scheduled
      for right total knee replacement. Her medical history included coronary artery
      disease, bronchial asthma, and previous surgery of lumbar laminectomy, but she
      had no neurological deficit before the operation. A 22-gauge spinal needle was
      inserted at the L 4-5 level and 4 ml of 0.5% bupivacaine with preservatives
      (Marcain 0.5%) was administered. The sensory block level was noted to L 1 and
      motor blockade of bilateral feet was achieved within 10 minutes. Anesthesia and
      operative courses were uneventful for 1.5 hours, and she complained severe low
      back pain but she could not move her thigh. Eight hours after administration of
      the anesthetic, her low back pain improved but the anesthetic effects showed no
      improvement. MRI showed no abnormality of the spinal cord on the following day,
      but her sensory loss level to L 1 and flaccid paralysis of bilateral lower
      extremities continued. Myelogram showed inflammation of cauda equina on the
      fourth day after the operation. She suffered from hydrocephalus two months later
      and MRI utilizing gadolinium as a contrast medium was consistent with a diagnosis
      of adhesive arachnoiditis of thoracolumbar region. Her neurological deficit
      showed no improvement for two years.

PMID- 10087829
TI  - [Total intravenous anesthesia for two patients complicated with myotonic
      dystrophy].
AB  - Total intravenous anesthesia with propofol, fentanyl and ketamine (PFK) was given
      to two patients complicated with myotonic dystrophy. Case-1: A 42-year-old female
      underwent a hemithyroidectomy. Anesthesia was induced slowly with intravenous
      ketamine 20 mg and propofol 60 mg. Her tracheal intubation was performed smoothly
      without any muscle relaxants. Anesthesia was maintained with propofol infusion of
      5 mg.kg-1.h-1, ketamine infusion of 0.3 mg.kg-1.h-1 and fentanyl 200 micrograms
      in total. She regained consciousness 20 minutes after the end of propofol
      infusion, and 15 minutes later, her trachea was extubated without any troubles.
      Case-2: A 41-year-old female underwent a removal of left parotid tumor.
      Anesthesia was induced slowly with ketamine 40 mg and propofol 100 mg
      intravenously. Anesthesia was maintained with propofol infusion of 5-10 mg.kg-1.h
      1, ketamine infusion of 0.5 mg.kg-1.h-1 and fentanyl 350 micrograms in total. No
      muscle relaxant was used through the surgical procedure. Emergence from
      anesthesia was observed 10 minutes after the end of propofol infusion and her
      trachea was extubated. When a nasogastric tube was pulled out, her respiration
      stopped suddenly and she was intubated again only for two hours without any
      troubles. In both cases their serum CPK levels and rectal temperatures were very
      stable. PFK method would be a choice for patients with myotonic dystrophy.

PMID- 10087830
TI  - [Differential epidural block for definitive diagnosis of snapping hip joint].
AB  - Snapping hip joint syndrome is defined as snapping phenomenon accompanied by
      motion of the hip joint. It occurs from various causes, and its diagnosis and
      treatment are often difficult. We gave anesthesia for surgery against snapping
      hip joint under patient's active motion for definitive regional diagnosis.
      Differential epidural block, which precludes pain while maintaining motor
      function, was performed by 0.25% bupivacaine, 0.5% lidocaine, and additional
      administration of fentanyl by 25 micrograms. Although the mechanism of
      differential nerve block remains to be unknown, the case suggests that effective
      pain block preserving motor function may be achieved by differential epidural
      block in combination with low concentration of local anesthetics and small dose
      of opioid.

PMID- 10087831
TI  - [Unexpected hyperkalemia during general anesthesia in three patients undergoing
      hepatic, cholangioler or pancreatic surgery].
AB  - Three patients developed unaccountable hyperkalemia during general anesthesia for
      pancreatectomy, hepatectomy, and cholangio-jejunostomy. The patients had normal
      preoperative renal function, serum potassium values, and intraoperative urine
      output. The surgical manipulations might have reduced portal venous and/or
      hepatic arterial blood flow resulting in the hepatic ischemia. Consequently,
      hepatic intra-cellular potassium might have leaked into the blood causing
      hyperkalemia. Anesthesiologists should be aware of the potential risk of
      hyperkalemia caused by surgical interventions on the liver and/or pancreas.

PMID- 10087832
TI  - [Hyperkalemia after irradiated blood transfusion].
AB  - A 70-yr-old woman was scheduled for hepatectomy and colectomy. We gave general
      anesthesia with N2O-O2-Isoflurane and continuous epidural block. About 4.5 hours
      after the start of the operation, 8 units of irradiated RBC-MAP were transfused.
      Then elevated T waves were noted and serum potassium was increased to 5.4 mmol.l
      1. The transfusion of RBC-MAP was stopped and calcium gluconate was administered
      immediately. Then serum potassium decreased to 4.3 mmol.l-1 and ECG returned to
      normal. During the operation, 10 units of irradiated RBC-MAP were transfused and
      8 units of them had been stored more than 1 week after the irradiation. We
      suspect that hyperkalemia was induced by high concentration of potassium in RBC
      MAP. Irradiation of blood products is an effective way to prevent post
      transfusion graft versus host disease. However, the increase in potassium is
      greater in the irradiated than nonirradiated RBC-MAP. We must pay attention to
      the high concentration of potassium in th eplasma of RBC-MAP stored after
      irradiation.

PMID- 10087833
TI  - [Anesthetic management of cesarean section for conjoined twins].
AB  - A 31-year-old female patient underwent cesarean section for conjoined twins under
      general anesthesia. In the 33rd week of pregnancy, MRI showed the twins to be a
      thoracopagus, whose hearts and livers are combined. The patient was not informed
      that her fetus combined. General anesthesia was induced with thiamylal 200 mg and
      vecuronium 8 mg in the presence of two pediatricians. Anesthesia was maintained
      with 66% nitrous oxide in oxygen until the delivery. Just after the delivery,
      methylergometrine maleate 0.2 mg, midazolam 5 mg, and fentanyl 100 micrograms
      were administered intravenously. PGF2 alpha was administered in the uterus
      because of inadequate contraction of the uterus. Apgar score was 0 point at both
      1 minute and 5 minutes. Autopsy showed their hearts and livers combined.
      Conjoined twins tend to die early after birth because of abnormality in their
      hearts. We selected general anesthesia for this case considering mother's
      feeling, and we successfully held intraoperative bleeding down with
      methylergometrine maleate and extra PGF2 alpha.

PMID- 10087834
TI  - [A case of Guillain-Barre syndrome with severe sciatica preceding motor paralysis
      in the lower extremities].
AB  - A 62-year-old man was referred to our clinic for a three-day history of
      intractable sciatic pain. The pain was so severe that he could not sleep for
      days. Initially there was no neuronal sign except for the pain, nor any
      abnormality in lumbar CT and MRI. Cerebrospinal fluid sampled on the third
      hospital day revealed elevated protein (192 mg.dl-1) with minimal cells. On the
      4th hospital day motor weakness of lower extremities appeared and he developed
      complete flaccid paraplegia in a week without loss of sensation. He was diagnosed
      as Guillain-Barre syndrome. For the relief of this pain, intermittent injection
      of 4 ml 0.25% bupivacaine from lumbar epidural catheter was started on the
      admission day. By using patient controlled analgesia system, we could treat his
      repetitive demand timely and well control the pain. The leg weakness started to
      recover slowly from the 13th hospital day and at the same time the pain started
      to diminish rapidly in a few days. From the 20th hospital day he started to have
      rehabilitation in walking and recovered completely in two months without
      complication. We should remember that sudden onset of severe pain is one of early
      symptoms of Guillain-Barre syndrome.

PMID- 10087835
TI  - [Effects of human atrial natriuretic polypeptide in a patient with acute
      pulmonary edema during living-related kidney transplantation].
AB  - A 19-year-old female was scheduled for living-related kidney transplantation
      under general anesthesia. Eight units of fresh frozen plasma were infused in 30
      minutes before the recanalization of renal vessels. Twenty minutes after the
      first urination, end-tidal-CO2 suddenly increased showing CVP of 18 mmHg. We
      considered that she had developed acute pulmonary edema. Continuous hANP infusion
      was initiated at the rate of 0.1 microgram.kg-1.min-1. By this infusion, end
      tidal-CO2 and CVP gradually decreased and operation was concluded successfully.
      This case demonstrates that hANP works also on the transplanted kidney.

PMID- 10087836
TI  - [The assessment of end-systolic pressure volume relationship in patients
      undergoing coronary artery bypass graft surgery].
AB  - Using transesophageal echocardiography (TEE) we assessed left ventricular end
      systolic elastance (Ees) during the pre- and post-cardiopulmonary bypass (CPB)
      periods in 10 patients undergoing an elective coronary artery bypass graft
      surgery. The end systolic volume of the left ventricle was obtained by TEE, and
      the end systolic pressure was obtained by the femoral artery pressure wave form.
      LVSWI decreased at post-CPB compared to the value at pre-CPB. There were no
      significant differences in cardiac output, ejection fraction and Ees between pre
      CPB and post-CPB period. Intraoperative end-systolic pressure-volume relationship
      may be clinically useful to assess left ventricular function and also useful to
      confirm anesthetic management in patients who has undergone an coronary artery
      bypass graft surgery.

PMID- 10087837
TI  - To what extent can the law control human cloning?
AB  - This paper explores the legal ramifications of human reproductive cloning in
      response to 'Dolly'--the first animal cloned from an adult cell. No attempt is
      made to address the complex moral and ethical dilemmas that will inevitably be
      consequential on future successes in human reproductive cloning. Some of the
      potential benefits of cloning are briefly summarized but discussion is focused
      primarily on the current state of the law in the UK and some other European
      jurisdictions. Attempts to legislate on human cloning in the US, the emerging
      role of the EU and amendments to the European Convention on Human Rights are
      outlined. The potential problems likely to be encountered in the enforcement of
      any global treaties or international regulations are highlighted. It is argued
      that attempting to control human cloning by imposing legal prohibition is futile
      and a pragmatic solution to this impending problem is required forthwith.

PMID- 10087838
TI  - The medical expert witness: time to regulate conflicts of interest.
AB  - Doctors are often asked to provide expert evidence for the courts. Whilst there
      is a considerable body of work in the legal literature, there is relatively
      little discussion and guidance in general medical literature. This is important
      as more doctors are drawn into the legal arena, and their ability to assist the
      court is a matter of consequence. The potential adverse effects in terms of the
      human, psychological and financial costs to the litigant parties, and the speed
      of access to justice, are considerable if the work is not done properly. Possible
      solutions to the present system are discussed and a set of guiding principles for
      acting as an expert witness is proposed.

PMID- 10087839
TI  - Assessing the expert: a call for reciprocal disclosure in Canada.
AB  - The requirement that the state disclose to an accused person all evidence in its
      possession which is not clearly irrelevant is a tenet fundamental to contemporary
      criminal law in Canada. In essence, the right to full answer and defence implies
      that the individual be allowed to completely understand the case which has been
      brought against him or her. This paper examines the concept of reciprocal
      disclosure, whereby the defence is obligated to provide evidence to the state.
      The confines of the ensuing discussion are limited to expert evidence and, more
      particularly, to psychiatric and psychological testimony. By arguing that early
      production of an expert's opinion advances rather than retards the interests of
      justice, the author attempts to debunk some of the myths which are used in
      Canadian legal circles to justify the suppression of opinion evidence by the
      defence until the last possible moment.

PMID- 10087840
TI  - Does psychiatric disorder affect the likelihood of violent offending? A critique
      of the major findings.
AB  - This paper reviews major studies that have examined a possible relationship
      between mental disorder and violent offending. Such studies have either examined
      (a) the prevalence of violence in the mentally disordered or (b) the prevalence
      of mental disorder among the violent. Indices of violence used include (a) arrest
      rate, (b) conviction rate and (c) prevalence of violent behaviour in psychiatric
      inpatients, representative community samples and birth cohorts. It is concluded
      that although the mentally disordered do face an elevated risk of violent
      behaviour/offending, this risk is largely confined to those suffering from severe
      or long-term psychotic symptoms or psychopathic disorders.

PMID- 10087841
TI  - A follow-up study of mentally disordered offenders after a court diversion
      scheme: six-month and one-year comparison.
AB  - The aim of this study was to investigate offenders' living patterns, quality of
      life, types of aftercare received and psychological well-being, following their
      diversion from one court diversion scheme in England. Sixty-five offenders were
      followed up after six months, 22 of whom were also followed up after one year.
      Their transient living patterns throughout these two periods were described.
      Their quality of life was found to be poor in that most did not have an
      occupation, nor did they receive education, and the life experiences during both
      periods were lower than that of standardized urban samples. There were no
      significant changes in their poor life experiences over the two periods. Over 55%
      of the 22 offenders still contacted their GPs regularly but there was a
      significant drop in those consulting hospital doctors. Only a small number of
      offenders had contact with the social services in these two periods and no
      significant differences were found between them. Their GHQ total scores went
      above cutoff point and the level of psychiatric conditions was similar in both
      periods.

PMID- 10087842
TI  - A controlled evaluation of assessments by doctors and nurses in a magistrates'
      court mental health assessment and diversion scheme.
AB  - In this study, assessments of prisoners by doctors and nurses were compared in a
      provincial magistrates' court mental health assessment and diversion scheme, and
      outcomes were compared with the outcomes of those for whom no assessments were
      available during a control period. Substance misuse was relatively common and
      psychosis uncommon in the prisoners referred. Assessment by doctors enabled
      magistrates to reduce remands in custody of persons suspected of suffering from
      mental disorder and to grant bail in more cases. Only a small proportion of
      prisoners were admitted to hospital and although doctors and nurses recommended
      out-patient treatment in many cases, the attendance rate was low. Doctors were
      more likely than nurses to identify prisoners with medical needs that needed to
      be brought to the attention of the prison health care service, and to recommend
      out-patient psychiatric treatment and identify relevant medicolegal issues.
      Prisoners assessed by nurses were less likely than those assessed by doctors to
      attend alcohol or drug treatment services if recommended to do so. Prisoners who
      were admitted to hospital after a remand in custody spent longer on remand if
      assessed by nurses compared with those assessed by doctors.

PMID- 10087843
TI  - Facial reconstruction: a case report and review of development of techniques.

PMID- 10087844
TI  - Biomechanics of judicial hanging: a case report.
AB  - A prisoner in Washington State in the United States of America appealed against
      sentence of death by hanging on the grounds that it was 'cruel and unusual' and
      hence contravened the Eighth Amendment of the US Constitution. The man weighed
      184 kg (406 lb) and it was suggested that the 'drop' proposed to effect judicial
      hanging might result in decapitation. This hypothesis was tested by applying
      simple biodynamic principles to the available data from past hangings. It was
      concluded that decapitation was a significant possibility.

PMID- 10087845
TI  - The place of bigamy in the pantheon of crime?
AB  - Bigamy is officially classified as a 'sex offence'. The offence is rare and
      attracts little criminological attention, and the reaction of the courts has
      become more lenient in recent years, yet the media coverage of bigamy remains
      quite pervasive. An analysis of the criminal career profile over 32 years (1963
      94) of the 42 bigamists convicted in 1973 indicates that they had no other
      convictions for bigamy and only two had convictions for a sex offence. Among the
      25 persons with other convictions, the crimes of theft/handling stolen goods and
      fraud and forgery predominate. In fact, the criminal careers of these bigamists
      are more similar to the criminal careers of white collar offenders than of other
      sex offenders. It is suggested that by looking at convicted bigamists' criminal
      careers one can more appropriately categorize the crime as deception, and in this
      context we need to consider how to respond to its perpetrators and victims.

PMID- 10087846
TI  - Trivial injuries, associated congenital anomaly and medicolegal interpretation of
      death.
AB  - Congenital hypoplasia of the odontoid process is a relatively rare phenomenon. A
      case is presented of a 12-year-old girl who was admitted to hospital with a
      history of having sustained trivial external injuries when falling after an
      alleged push. Later, she developed signs of compression of the spinal cord in the
      cervical region, resulting in quadriplegia and muscle wasting. A laminectomy was
      performed to relieve the symptoms but the child died 2 1/2 months later. Autopsy
      revealed a congenital anomaly of the atlas and axis vertebrae in the form of
      hypoplasia of the dens. The case being associated with a criminal assault, the
      post-mortem analysis and autopsy were significant in resolving medicolegal issues
      pertaining to the assailant, the operating surgeon and the law-enforcement
      agencies.

PMID- 10087847
TI  - Vitreous humor as an alternative sample to blood for the supercritical fluid
      extraction of morphine and 6-monoacetylmorphine.
AB  - The use of vitreous humor as an alternative sample to blood was investigated for
      the detection of heroin abuse by quantifying levels of morphine and 6
      monoacetylmorphine (6-MAM) in post-mortem samples. The levels achieved in each of
      the two toxicological specimens were compared on a case-to-case basis to
      determine if a correlation existed. A total of 20 positive morphine cases were
      examined. In general, the levels of morphine in blood were higher than in the
      corresponding vitreous humor samples, with some correlation existing. 6-MAM was
      found in 15 blood samples and 17 vitreous humor samples. Although no correlation
      was found between the levels of 6-MAM in blood and vitreous humor, the latter may
      still be used for verification of heroin abuse.

PMID- 10087848
TI  - Accidental decapitation: an unusual injury to a passenger in a vehicle.
AB  - A case of decapitation of a vehicle passenger in an accident on a highway is
      reported. Evaluation of roadside evidence and the deceased's injuries revealed
      that the victim was partially ejected from a broken passenger-side window as the
      vehicle spun out of control, decapitation being due to the impact of his head
      against a barrier stanchion on the shoulder of the road. An unfastened seat-belt,
      high-speed driving and the construction of the road barrier were contributory
      factors.

PMID- 10087849
TI  - A change of direction in the disposal of mentally disordered offenders: the
      impact of the Crime (Sentences) Act 1977.

PMID- 10087850
TI  - Intoximeter 3000 and the four minute fallacy.

PMID- 10087851
TI  - Implicit memory for phonological processes in visual stem completion.
AB  - Four experiments were conducted investigating the role of phonology in repetition
      priming. Experiment 1 used a cross-modal priming paradigm in which participants
      made semantic judgments about spoken words and then performed a visual stem
      completion task. In Experiments 2-4, both the primes and the test stems were
      presented visually. The results of the first three experiments revealed that
      priming transfers across interpretations of a homophone. That is, seeing or
      hearing week primes both week and weak. The results of Experiment 4 showed that
      homophone priming cannot be attributed to the orthographic similarity of
      homophonic words. Together, these results indicate that repetition priming on a
      visual word completion task includes a phonological component.

PMID- 10087852
TI  - Manipulation of familiarity reveals a necessary lexical component of the word
      stem completion priming effect.
AB  - These experiments were motivated by the idea that many types of nondeclarative
      memory are by-products arising from the plasticity that is inherent in much of
      the nervous system. We hypothesized that two types of repetition priming, word
      stem completion (WSC) priming and perceptual identification (PI) priming, rely on
      different mechanisms because the WSC task and the PI task engage different
      cognitive and brain processes. We tested this hypothesis by manipulating word
      familiarity. The results, impaired WSC priming but intact PI priming with
      unfamiliar words, indicate that WSC priming relies primarily on a modification
      mechanism, whereas PI priming relies primarily on an acquisition mechanism. Our
      conclusions are consistent with component processes theories of nondeclarative
      memory.

PMID- 10087853
TI  - Nonstrategic subjective threshold effects in phonemic masking.
AB  - Three backward-masking experiments demonstrated that the magnitude of the
      phonemic mask reduction effect (MRE) is a function of subjective threshold and
      that the magnitude is also independent of stimulus-based response strategies. In
      all three experiments, a target word (e.g., bake) was backward masked by a
      graphemically similar nonword (e.g., BAWK), a phonemically similar nonword (e.g.,
      BAIK), or an unrelated control (e.g., CRUG). Experiments 1 and 2 had a low
      percentage (9%) of trials with phonemic masks and differed only in baseline
      identification rate. Experiment 3 controlled baseline identification rate at
      below and above subjective threshold levels, with 9% phonemic trials. The results
      were that identification rates were higher with phonemic masks than with
      graphemic masks, irrespective of the low percentage of phonemic trials. However,
      the magnitude of the phonemic MRE became large only when the baseline
      identification rate was below subjective threshold. The pattern of the phonemic
      MRE was interpreted as a result of rapid automatic phonological activation,
      independent of stimulus-based processing strategies.

PMID- 10087854
TI  - The importance of semantic similarity to the irrelevant speech effect.
AB  - Irrelevant speech disrupts immediate recall of a short sequence of items. Salame
      and Baddeley (1982) found a very small and nonsignificant increase in the
      irrelevant speech effect when the speech comprised items semantically identical
      to the to-be-remembered items, leading subsequent researchers to conclude that
      semantic similarity plays no role in the irrelevant speech effect. Experiment 1
      showed that strong free associates of the to-be-remembered items disrupted serial
      recall to a greater extent than words that were dissimilar to the to-be
      remembered items. Experiment 2 showed that this same pattern of disruption in a
      free recall task. Theoretical implications of these findings are discussed.

PMID- 10087855
TI  - Reversing the phonological similarity effect.
AB  - The phonological similarity effect--poor retention of order for lists of similar
      sounding items--is a benchmark finding in the short-term memory literature. In
      our first two experiments, we show that the effect actually reverses following
      relatively brief periods of distraction, yielding better order retention for
      similar than for dissimilar lists, provided that different items are used on
      every trial. In Experiment 3, the same items were used on every trial and similar
      lists produced poorer performance across all three retention intervals. The
      results are interpreted from a general discrimination framework: Items are viewed
      as occupying positions in a multidimensional space defined by list and within
      list dimensions.

PMID- 10087856
TI  - Order information in short-term memory and time estimation.
AB  - In previous experiments, the amount of interference between time production and
      visual or memory search tasks was shown not to be related to the level of
      difficulty of the search task per se, but instead to the amount of processing in
      short-term memory required in the search task. The first experiment of the
      present study verified whether the amount of interference between time production
      and a short-term memory task may be related to the level of difficulty of the
      short-term memory task. Two versions of a memory task, with and without
      processing of order information, were combined with a temporal interval
      production task in a concurrent processing condition. As is shown in a control
      reaction time task, processing order information increased the level of
      difficulty of the memory search task. In the concurrent processing condition, the
      interference between short-term memory processing and time production was
      stronger when the level of difficulty of the short-term memory search task was
      increased by requiring that order information be processed. The results of
      Experiment 2 showed that the amount of interference between a similar short-term
      memory task and time production seems not to be related to the amount of order
      information that must be maintained during the time production task. This
      dissociation between the effects of processing and the maintenance of order
      information is compatible with a similar dissociation, observed in previous
      experiments, between the effects of processing and those of maintaining item
      information in short-term memory on concurrent time production.

PMID- 10087857
TI  - Processing irrelevant location information: practice and transfer effects in
      choice-reaction tasks.
AB  - Left or right keypresses to a relevant stimulus dimension are faster when the
      stimulus location, although irrelevant, corresponds with that of the response
      than when it does not. This phenomenon, called the Simon effect, persisted across
      1,800 trials of practice, although its magnitude was reduced. Practice with the
      relevant stimulus dimension presented at a centered location had little influence
      on the magnitude of the Simon effect when irrelevant location was varied
      subsequently, and practice with location irrelevant prior to performing with
      location relevant slowed responses. After practice responding to stimulus
      location with an incompatible spatial mapping, the Simon effect was reversed
      (i.e., responses were slower when stimulus location corresponded with response
      location) when location was made irrelevant. When the response keys were labeled
      according to the relevant stimulus dimension (the Hedge and Marsh [1975] task
      variation), this reversal from practice with a spatially incompatible mapping was
      found for both the congruent and the incongruent relevant stimulus-response
      mappings. Thus, task-defined associations between stimulus location and response
      location affect performance when location is changed from relevant to irrelevant,
      apparently through producing automatic activation of the previously associated
      response.

PMID- 10087858
TI  - Effects of similarity and practice on speeded classification response times and
      accuracies: further tests of an exemplar-retrieval model.
AB  - Observers were tested in a perceptual category-learning experiment in which they
      were instructed to make classification decisions as rapidly as possible without
      making errors. Nosofsky and Palmeri's (1997b) exemplar-based random walk (EBRW)
      model of speeded classification was tested for its ability to fit the
      classification response times and accuracies. The authors demonstrated that the
      EBRW model provided good quantitative fits to the mean response times and
      accuracies associated with individual objects as a function of their locations in
      a multidimensional similarity space and as a function of practice in the task.
      Preliminary evidence was also obtained that stimulus-specific adjustments in the
      random walk response criteria may have occurred during the course of learning.

PMID- 10087859
TI  - The inadvertent use of prior knowledge in a generative cognitive task.
AB  - In four experiments with 332 participants, participants were asked to generate
      novel nonwords for English categories. When participants were shown examples
      embedded with regular orthographic structures, participants' nonwords tended to
      conform orthographically to the examples, despite instructions to avoid using
      features of the examples. The effect was found with immediate testing
      (Experiments 1) and delayed testing (Experiment 2). The effect was also found
      with arbitrary features (Experiments 1-4), as well as with naturally occurring
      orthographic regularities (Experiment 4). Participants had difficulty avoiding
      the use of this prior knowledge, despite being able to list the features they
      were asked to avoid (Experiment 3). The results are discussed in terms of the
      inadvertent use of prior knowledge in generative cognitive tasks.

PMID- 10087860
TI  - A beautiful day in the neighborhood: what factors determine the generation effect
      for simple multiplication problems?
AB  - In four experiments, we examined the generation effect for the free recall of
      simple multiplication answers. Large-product-size problems showed a consistent
      generation-effect advantage over small-product-size problems, except when each
      answer was generated twice, via two different sets of operands (Experiment 2).
      Also, measures of problem-solution time and strategy use accounted for the large
      product-size advantage. Across experiments, however, small-product-size problems
      (but not large-product-size problems) showed considerable variation in the size
      of their generation effect. We discovered that solving small-product-size
      problems via direct memory retrieval increased the episodic recall probability of
      other problems that were near neighbors to the generated answer, and we attribute
      this result to a spreading activation mechanism in semantic memory. A measure of
      neighbor activations, combined with RT to solve each problem, accounted for 51%
      of the observed generation-effect variance.

PMID- 10087861
TI  - Repetition priming in simple addition depends on surface form and typicality.
AB  - Repetition priming and recognition memory for numbers were measured in four
      experiments using single-digit addition. Results of the first two experiments
      indicate that when numbers were presented as number words and dot configurations,
      preexposure of the same problem in the same notation produced greater reaction
      time benefit than did preexposure of the same problem in Arabic-digit notation.
      In contrast, when numbers were presented as Arabic digits, preexposure of the
      same problem in Arabic digit, number word, and dot notation produced the same
      amount of priming. In the third experiment, priming was shown to be greatest, for
      all three notations, when the task performed on preexposure trials (addition or
      multiplication) matched the task performed on repetition trials (addition).
      Results of the fourth experiment, measuring recognition memory, were comparable
      to the priming results in the sense that memory was superior when notation
      matched across repetitions if the test involved number words and dot
      configurations but not Arabic digits. These data are interpreted in terms of
      models of numerical cognition, and they support the hypothesis that the influence
      of surface form on repetition priming depends on the typicality of the input for
      the task.

PMID- 10087862
TI  - Shades of the mirror effect: recognition of faces with and without sunglasses.
AB  - A mirror effect was found for a stimulus manipulation introduced at test. When
      subjects studied a set of normal faces and then were tested with new and old
      faces that were normal or wearing sunglasses, the hit rate was higher and the
      false alarm rate was lower for normal faces. Hit rate differences were reflected
      in remember and sure recognition responses, whereas differences in false alarm
      rates were largely seen in know and unsure judgments. In contrast, when subjects
      studied faces wearing sunglasses, the hit rate was greater for test faces with
      sunglasses than for normal faces, but there was no difference in false alarm
      rates. These findings are problematic for single-factor theories of the mirror
      effect, but can be accommodated within a two-factor account.

PMID- 10087863
TI  - The prototype effect in face recognition: extension and limits.
AB  - The prototype effect in face recognition refers to a tendency to recognize the
      face corresponding to the central value of a series of seen faces, even when this
      central value or prototype has not been seen. Five experiments investigated the
      extension and limits of this phenomenon. In all the experiments, participants saw
      a series of faces, each one in two or more different versions or exemplars, and
      then performed a recognition test, including seen and unseen exemplars and the
      unseen prototype face. In Experiment 1, a strong prototype effect for variations
      in feature location was demonstrated in oldness ratings and in a standard old/new
      recognition test. Experiments 2A and 2B compared the prototype effect for
      variations in feature location and variations in head angle and showed that, for
      the latter, the prototype effect was weaker and more dependent on similarity than
      for the former. These results suggest that recognition across feature variations
      is based on an averaging mechanism, whereas recognition across viewpoint
      variations is based on an approximation mechanism. Experiments 3A and 3B examined
      the limits of the prototype effect using a face morphing technique that allows a
      systematic manipulation of face similarity. The results indicated that, as the
      similarity between face exemplars decreases to the level of similarity between
      the faces of different individuals, the prototype effect starts to disappear. At
      the same time, the prototype effect may originate false memories of faces that
      were never seen.

PMID- 10087864
TI  - (Non)complementary updating of belief in two hypotheses.
AB  - Past research has led to the conclusion that two competing hypotheses are
      represented dependently, and confidence in them is updated in a complementary
      manner. It is argued here that confidence in two hypotheses can be represented
      either dependently or independently. Changes in confidence in the former case are
      always complementary, but changes in the latter case are complementary only under
      certain conditions. In three simulated medical diagnosis experiments, subjects
      learned about two illnesses in a manner expected to lead to either dependent or
      independent confidence. They were then presented with two symptoms sequentially
      (for each of several patients), updating confidence after each. Experiment 1
      demonstrated that changes in confidence in the two illnesses were largely
      complementary for subjects with dependent, but not independent, confidence.
      Experiment 2 showed that encouraging consideration of the alternative led to more
      complementary changes for subjects with independent confidence. Experiment 3
      succeeded in producing complementary changes from these subjects. Thus,
      complementarity does not imply dependent confidence, nor does independent
      confidence imply non-complementarity.

PMID- 10087865
TI  - Source of arousal and memory for detail.
AB  - Two questions about the relationship between arousal and memory were
      investigated: First, does the source of arousal influence memory, and, second,
      what impact does arousal have on memory for detail? In Experiment 1,
      physiological arousal (running or not running in place) was factorially combined
      with emotional arousal (viewing a neutral or an emotional slide sequence).
      Recognition memory was tested for gist, central detail, and background detail.
      Experiments 2 and 3 were similar to Experiment 1, with the exception that a cued
      recall task was used in Experiment 2 and physiological arousal was manipulated
      with stationary biking in Experiment 3. The results of these experiments
      indicated that physiological arousal had little impact on memory and that
      emotional arousal led to improvements in memory for both central and background
      detail. Overall, these results supported the notions that the source of arousal
      is an important determinant of an event's memorability (Christianson, 1992a) and
      that emotional arousal serves to enhance the scope of memory (i.e., flashbulb
      memory; Brown & Kulik, 1977).

PMID- 10087866
TI  - The 1997 amendments to the IDEA: improving the quality of special education for
      children with disabilities.

PMID- 10087868
TI  - [Airway autonomic nervous system dysfunction and asthma].
AB  - Airways are richly innervated by 4 nervous systems, namely adrenergic,
      cholinergic, inhibitory nonadrenergic noncholinergic (i-NANC), and excitatory
      NANC (e-NANC) nervous systems. Dysfunction or hyperfunction of these systems may
      be involved in the inflammation or airway hyperresponsiveness observed in
      asthmatic patients. The cholinergic nervous system is the predominant neural
      bronchoconstrictor pathway in humans. Airway inflammation shows exaggerated
      acetylcholine release from cholinergic nerves via dysfunction of the
      autoreceptor, muscarinic M2, which is possibly caused by major basic protein or
      IgE. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) released from i
      NANC nerves act as an airway smooth muscle dilator. The effects of VIP and NO are
      diminished after allergic reaction by inflammatory cell-mediated tryptase and
      reactive oxygen species. Thus, in asthmatic airways, the inflammatory change
      mediated neural imbalance may result in airway hyperresponsiveness. Tachykinins
      derived from e-NANC nerves have a variety of actions including airway smooth
      muscle contraction, mucus secretion, vascular leakage, and neutrophil attachment,
      and may be involved in the pathogenesis of asthma. Since tachykinin receptor
      antagonists are effective for bradykinin- and exercise-induced
      bronchoconstriction in asthmatic patients, these drugs may be useful for asthma
      therapy.

PMID- 10087869
TI  - [Influence of beclomethasone dipropionate inhalation therapy on respiratory
      bacterial infection in patients with an acute exacerbation of COPD].
AB  - The aim of this clinical study was to investigate the influence of beclomethasone
      dipropionate (BDP) inhalation therapy on respiratory bacterial infections in
      patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).
      We studied 30 patients who had been admitted twice, (before and after the
      beginning BDP inhalation therapy) to our hospital because of an exacerbation of
      COPD by respiratory tract infection. No differences were observed before and
      after BDP inhalation therapy in values for PaO2, PaCO2, body temperature, CRP,
      WBC count, number of admission days, and bacterial culture of sputum on
      admission. These results suggest that BDP inhalation therapy has little influence
      on respiratory bacterial infection during exacerbation of COPD.

PMID- 10087870
TI  - [Usefulness of power Doppler sonography for the assessment of subpleural
      lesions].
AB  - We investigated the usefulness of color Doppler power mode imaging for the
      assessment of subpleural lesions in 48 patients (27 with pneumonia, 4 with
      pulmonary abscesses, 12 with primary lung cancer, and 5 with metastatic lung
      cancer). We classified the patterns obtained by color flow imaging of subpleural
      lesions into six groups: type 0, no color flow; type I, spotty color flow; type
      II, linear color flow; type III, branchy color flow; and type IV, tortuous color
      flow, with type IV-A, for partial tortuous flow and type IV-B, for general
      tortuous flow. The color Doppler power mode proved better than velocity mode in
      terms of ability to generate clear color flow patterns. Color flow patterns
      obtained in power mode on the patients with pneumonia differed significantly from
      the patterns obtained on the lung cancer patients. Although the color flow
      patterns observed in power mode differed significantly for the benign and
      malignant groups, no statistically significant differences were observed in
      velocity mode. These findings illustrated the usefulness of color Doppler power
      mode imaging as a means of diagnosing benign and malignant subpleural lesions.

PMID- 10087871
TI  - [Clinical study of 8 patients with round atelectasis associated with asbestos
      exposure].
AB  - Matsubase town (where our hospital is located) has a history of environmental
      exposure to asbestos. We reviewed the clinical and radiological features of 8
      patients with round atelectasis associated with asbestos exposure who had been
      examined at our hospital between 1988 and 1997. The subjects were followed up
      over a period ranging from 6 months to 10 years (mean: 54 months). Round tumors
      were detected in 6 of the patients by chest CT scans but not by chest X-ray
      films. Five of those patients underwent transbronchial lung biopsies, and 1 was
      examined by bronchography. Two patients had a history of pleural effusion. Seven
      of the patients exhibited round atelectasis in their lower lung fields. The
      clinical course of round atelectasis was unchanged in all patients. Although
      round atelectasis is sometimes suspected of being bronchial carcinoma, it can be
      diagnosed without thoracotomy, on the basis of the patient's medical history and
      a careful examination of radiological findings.

PMID- 10087872
TI  - [Expression of hepatocyte growth factor by activated eosinophiles in inflammatory
      lung tissue].
AB  - Hepatocyte growth factor (HGF) plays a multifunctional role in the regeneration
      of alveolar type-II and other epithelial cells. HGF is produced by various kinds
      of mesenchymal cells, including polymorphonuclear granulocytes. However, it was
      not evident that eosinophiles produce HGF. In this investigation, we utilized
      immunohistochemical techniques to show that Eol-1 cells, an eosinophilic leukemia
      cell line, as well as activated eosinophiles in inflammatory lung tissue, produce
      HGF. It was also shown that IL-5 induced the production of HGF by peripheral
      eosinophiles in vitro. These findings suggest that, in inflammatory lung
      diseases, eosinophiles activated in the presence of IL-5 produce not only tissue
      injurious substances (e.g., eosinophilic cationic protein, major basic protein,
      and peroxidase) but also HGF; and that eosinophiles may play a role in the
      regeneration of injured lung tissue through the production of HGF.

PMID- 10087873
TI  - [Effectiveness of isoniazid inhalation in patients with endobronchial
      tuberculosis].
AB  - The clinical effectiveness of isoniazid (INH) inhalation was studied
      retrospectively in 34 patients with endobronchial tuberculosis. Diagnoses of
      endobronchial tuberculosis and assessments of bronchial stenosis were based on
      bronchoscopic examinations. We divided the patients into 2 groups: 13 who
      received systemic chemotherapy for lung tuberculosis only, and 21 who received
      systemic chemotherapy combined with INH inhalation (200 mg/day). No significant
      differences distinguished the groups with respect to duration of positive sputum
      culture or ESR normalization. However, a significant alleviation of bronchial
      stenosis and earlier reduction of respiratory symptoms were observed in the
      patients who received systemic chemotherapy with INH inhalation. We concluded
      that INH inhalation in addition to standard therapy for lung tuberculosis is
      effective in patients with endobronchial tuberculosis.

PMID- 10087874
TI  - [Itraconazole-induced hypokalemia in a patient with pulmonary aspergilloma].
AB  - An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary
      aspergilloma. A new azole antifungal agent, D 0870, was administered to the
      patient for 7 days orally, and itraconazole (400 mg/day) was started on March 5,
      1997. After 1 month of chemotherapy, facial and pretibial edema were observed and
      the patient's serum potassium concentration decreased to 2.5 mEq/l. A chest
      radiograph disclosed cardiomegaly with cardiac effusion and right pleural
      effusion on admission. The serum potassium concentration rose after the cessation
      of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks
      after admission. Although reports of hypopotassemia induced by ITCZ are rare, we
      concluded that blood concentrations should be monitored more carefully when
      treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.

PMID- 10087875
TI  - [Acute empyema caused by Streptococcus milleri in early pregnancy].
AB  - A 40-year-old woman was admitted to our department complaining of left lateral
      chest pain and fever. She smoked 10 cigarettes per day. Chest radiographs
      revealed increased density in the upper left lung field and air-fluid level in
      the lower left lung field. A diagnosis of acute empyema was made, because pus was
      aspirated by thoracentesis. Streptococcus intermedius (Streptococcus milleri
      group) was isolated from samples of pleural effusion. The patient was
      successfully treated with a combination of antibiotics and surgical drainage. It
      became clear after discharge that she was in her 6th week of pregnancy.
      Laboratory findings showed decreased lymphocyte transformation in the PHA and Con
      A tests. We reasoned, therefore, that smoking and decreased cellular immunity due
      to pregnancy might be causes of bacterial infections such as empyema.

PMID- 10087876
TI  - [Holter electrocardiogram monitoring as an indicator of cardiac involvement of
      sarcoidosis].
AB  - Sarcoidosis was diagnosed in a 55-year-old non-smoking woman because biopsy
      specimens of a subcutaneous tumor in her right cheek disclosed a noncaseating
      epithelioid granuloma. The patient had experienced exertional dyspnea and
      palpitation. Two months later, she was admitted because a Holter
      electrocardiogram (ECG) revealed bradycardia, 2:1 atrioventricular block (Mobitz
      II type) and ventricular premature beat (1.091 beats/day). ECG findings on
      admission changed from 2nd-degree to 3rd-degree atrioventricular block. A
      permanent pacemaker was implanted and the patient's symptoms subsided.
      Mediastinal uptake of Gallium-67 was observed and a defect of the cardiac septum
      was disclosed by Thalium-201 scintigram. Closer examination of the first Holter
      ECG revealed a Mobitz II type 2:1 atrioventricular block for about 3 minutes a
      day. Although the findings of the first Holter ECG initially disclosed a 2nd
      degree atrioventricular block in our patient, a complete block developed within
      about 2 months after admission. In the follow-up of sarcoidosis patients, it
      therefore seems important to not only evaluate Holter ECG findings carefully, but
      repeat the examination at regular intervals.

PMID- 10087877
TI  - [Lung cancer detected in a patient under age 40 treated for pneumothorax].
AB  - We report a case of lung cancer in a relatively young patient who presented
      pneumothorax. A 31-year-old man complaining of pressure in his left chest was
      admitted with left pneumothorax disclosed on X-ray film. Although pleural
      drainage was performed for a week, the left lung did not expand well, and
      surgical treatment was required. During surgery, a tumor (1.5 x 1.0 cm in size)
      was discovered in the upper lobe of the left lung (S3). Histopathological
      examination revealed that it was a large cell carcinoma. People under the age of
      40 account for only a small fraction of the entire lung cancer patient
      population. Pneumothorax occurs together with lung cancer, especially in people
      under age 40. We reasoned that lung cancer should be considered a possible
      complication in patients under 40 who experience recurrent or prolonged bouts of
      pneumothorax.

PMID- 10087878
TI  - [An autopsy case of Goodpasture's syndrome with P-ANCA and systemic vasculitis].
AB  - A 72-year-old woman was admitted because of anorexia and dyspnea. She was given a
      diagnosis of pulmonary hemorrhage and renal failure. Despite treatment with high
      dose steroid and hemodialysis, the patient died of disseminated intravascular
      coagulation on the 9th hospital day. Autopsy revealed intra-alveolar hemorrhage,
      crescentic glomerulonephritis, and systemic vasculitis with fibrinoid necrosis. A
      direct immunofluorescence study demonstrated linear deposition of IgG along the
      glomerular basement membrane (GBM). Both anti-GBM antibody and anti-neutrophil
      cytoplasmic antibody with perinuclear pattern (P-ANCA) were detected in the
      patient's serum by enzyme immunoassay. Goodpasture's syndrome with P-ANCA was
      diagnosed. There has been some controversy as to whether vasculitis occurs in
      patients with Goodpasture's syndrome. This was a rare example of well-documented
      Goodpasture's syndrome with P-ANCA and systemic vasculitis, the exact etiologic
      relationships among which remain to be clarified.

PMID- 10087879
TI  - [Pulmonary metastatic malignant phyllodes tumor showing multiple thin walled
      cavities].
AB  - A 52-year-old woman who had undergone a partial mastectomy 1 year earlier because
      of benign phyllodes tumor was admitted because of dry cough and abnormal chest
      radiograph findings. Chest computed tomograms demonstrated multiple thin-walled
      cavities and nodules. Clinical examinations and transbronchial biopsy specimens
      failed to provide a conclusive diagnosis. However, the pulmonary thin-walled
      cavities enlarged, and a nodular shadow revealed cavitary formation. An open lung
      biopsy was performed to diagnose the pulmonary lesions. Although biopsy specimens
      disclosed the infiltration of poorly differentiated adenocarcinoma cells in
      pleura and pulmonary parenchyma, no primary site was detected. The patient did
      not respond to systemic chemotherapy (CDDP and VP-16), and died of respiratory
      failure due to advanced pulmonary metastasis. Autopsy demonstrated marked tumor
      invasion of the lungs, myocardium, and bone. We analyzed malignant cells in lung
      tissues at autopsy by immunohistochemistry, and found identical malignant cells
      in surgical samples obtained during the patients earlier mastectomy. A diagnosis
      of pulmonary metastasis from malignant phyllodes tumor of the breast was made.
      Thin walled cavitary lesions from malignant phyllodes tumor are rare; however,
      pulmonary metastasis of malignant phyllodes tumor should be considered one
      disease that exhibits thin-walled cavities as a radiographic manifestation.

PMID- 10087880
TI  - [Primary racemose hemangioma of bronchial artery].
AB  - A 38-year-old woman was admitted to the hospital because of massive hemoptysis. A
      chest X-ray film disclosed an infiltrative shadow. A bronchoscopic examination
      revealed a small, pulsatile, papillary protrusion in the orifice of the middle
      lobe bronchus, and massive bleeding from the protrusion was observed during the
      examination. Bronchial arteriography showed convolution and mild
      hypervascularization of the right bronchial artery. A middle lobectomy was
      performed, and the protrusion was histologically shown to be a primary racemose
      hemangioma of the bronchial artery.

PMID- 10087881
TI  - [Mediastinal and hilar lymph node of cancer unknown origin: 3 case reports].
AB  - We encountered three rare cases of cancer of unknown origin affecting the
      mediastinal and hilar lymph nodes. Patient 1 was a 63 year-old man. Chest X-ray
      and CT films revealed an enlarged right hilar lymph node. A right mediastinal and
      hilar lymphadenectomy was performed. The histological diagnosis was metastatic
      squamous cell carcinoma (SCC). SCC of the right upper lobe appeared 34 months
      after the operation, requiring a right pneumonectomy. Patient 1 was alive 43
      months after his first operation. Patient 2 was a 73 year-old man in whom left
      mediastinal and hilar lymph node swelling had been detected. A mediastinoscopy
      and lymph node biopsy were performed. The histological findings resulted in a
      diagnosis of metastatic small cell carcinoma. Chemotherapy was initiated, and the
      patient was alive 5 months after the biopsy procedure, Patient 3 was a 57 year
      old man in whom right mediastinal and hilar lymph node swelling had been
      disclosed by chest CT scans. We performed a medianosternotomy and mediastinal and
      right hilar lymphadenectomy. Histologically, the diagnosis was metastatic
      adenocarcinoma. After the operation, radiation therapy was performed on the
      patient's mediastinum. Patient 3 was alive 5 months after the initial operation.
      The patients were given diagnoses of T0N1 or T0N2 lung cancer.

PMID- 10087882
TI  - [Undiagnosed lung cancer complicated by intracavitary aspergillosis].
AB  - A 54-year-old man was treated with an antifungal agent (itraconazole) for post
      tuberculous intracavitary aspergillosis. Though clinical and radiological
      findings indicated that the patient's symptoms had gone into remission,
      aspergillosis recurred 4 months after the cessation of antifungal chemotherapy,
      requiring that the patient undergo an operation. Intraoperative and pathological
      findings revealed a squamous cell carcinoma contiguous to the cavity containing
      the aspergilloma. Though a few cases of aspergilloma within cavitating pulmonary
      carcinomas have been reported in the literature, the case of lung cancer we
      report was thought to arise from preformed lung scars surrounding a post
      tuberculous cavity that contained an aspergilloma. Although conclusive
      distinctions between neoplasms and fungal infections are difficult to make,
      careful observation of the radiographic features is necessary when treating
      patients with fungus ball-type aspergillosis.

PMID- 10087883
TI  - [Genetic diagnosis of familial colorectal tumor by using a budding yeast cells].

PMID- 10087884
TI  - [The affect of Helicobacter pylori and bile acids as the pathogenesis of
      gastritis of the remnant stomach after distal partial gastrectomy].
AB  - AIMS: After distal partial gastrectomy with Billroth I reconstruction, gastritis
      of the remnant stomach was previously considered to be caused by bile reflux.
      However, since in 1982, Helicobacter pylori (HP) was discovered and it was found
      that this organism caused for many types of stomach diseases. The affect of HP
      must also be examined in the remnant stomach. In a current study, we examined the
      existence of HP and explored bile reflux as a pathogenesis of gastritis of the
      remnant stomach after distal partial gastrectomy. PATIENTS AND METHODS: The
      subjects were 56 patients who underwent gastrectomy. The existence of HP was
      investigated before and after gastrectomy. At postoperative gastroscopy, we
      examined histological findings of remnant gastritis and total bile acid (TBA)
      concentration in the gastric juice. Then we assessed the effect of HP and TBA on
      gastritis regarding the time after gastrectomy. RESULT: HP was positive in 75% of
      the patients before the operation and in 37.5% after the operation. The HP
      positive ratio was significantly lower in patients more than 5 years after
      gastrectomy than in those within 5 years. Inflammatory cell infiltration of the
      remnant gastric mucosa was more prominent in HP positive patients than in HP
      negative patients. In HP positive remnant stomachs, the TBA concentration of the
      gastric juice was lower than in HP negative remnant stomachs. CONCLUSION: Within
      5 years after distal partial gastrectomy, gastritis of the remnant stomach was
      mainly caused by HP.

PMID- 10087885
TI  - [The efficacy and prognosis of transcatheter chemoembolization for hepatocellular
      carcinoma in the elderly].
AB  - Four hundred and twenty-one patients with hepatocellular carcinoma who firstly
      underwent transcatheter arterial chemoembolization were divided into three groups
      as "younger" (32-69yr-old, n = 340), "elderly" (70-79yr-old, n = 74) and "super
      elderly" (80-89yr-old, n = 7). Between "younger" and "elderly," clinical stage of
      underlying liver disease, stage of hepatocellular carcinoma and tumor necrosis
      rate at first treatment did not differ significantly. In these two groups, the
      first year survival rates were 83.2, 79.7%, the third year survival rates were
      47.2, 36.5% and the fifth year survival rates were 22.9, 14.5% respectively.
      Cumulative survival rate of the "elderly" was similar to the "younger". Factors
      significantly affecting the survival period included advanced clinical stage of
      underlying liver disease and hepatocellular carcinoma, poor tumor necrosis at the
      first treatment and high serum alpha-fetoprotein level in the "younger" and high
      alpha-fetoprotein, advanced stage of hepatocellular carcinoma and presence of
      other than liver disease in "elderly". Transarterial chemoembolization is useful
      for the treatment of hepatocellular carcinoma in the "elderly" with the attention
      for their underlying diseases.

PMID- 10087886
TI  - [Serial hepatic and splenic volumetry in acute severe hepatitis].
AB  - In this study, we elucidate a relationship between final outcome and changes in
      hepatic and splenic volume in patients with acute severe hepatitis. The subjects
      were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30
      with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver
      and spleen volume were measured by CT initially on hospitalization and
      subsequently 1 to 40 days after hospitalization, and the scans were analyzed
      retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non
      survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased,
      spleen volume increased in none of the survivors, whereas it increased in 11 of
      the 14 non-survivors. In survivors there was a close parallelism between changing
      rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001).
      These observations suggest that the decrease of liver volume accompanied by that
      of spleen volume implies a good prognosis, while the decrease without such
      accompaniment implies a bad prognosis.

PMID- 10087887
TI  - [A case of tailgut cyst].

PMID- 10087888
TI  - [A case of intraabdominal abscess leading to the discovery of intestinal
      tuberculosis].

PMID- 10087889
TI  - [A case of ulcerative colitis associated with interstitial pneumonitis during
      administration of 5-aminosalicylic acid].

PMID- 10087890
TI  - [Gastric antral vascular ectasia (GAVE) in a patient with primary biliary
      cirrhosis: seven-year follow-up].

PMID- 10087891
TI  - [A case of mediastinal pancreatic pseudocysts successfully treated with
      somatostatin analogue].

PMID- 10087892
TI  - [A case of adenosquamous pancreatic cancer with high serum level of parathyroid
      related protein in which both primary and liver metastatic lesions showed
      remarkable cystic changes].

PMID- 10087893
TI  - [A case of non-functioning malignant islet cell tumor with egg-shaped
      calcification].

PMID- 10087894
TI  - [A case of biliary ascariasis removed by endoscopic procedure].

PMID- 10087895
TI  - [Parental assessment of a psycho-oncologic treatment concept in pediatrics].
AB  - Treatment-accompanied psychosocial care of pediatric cancer patients and their
      families is quite established nowadays. In this study a family-oriented
      psychosocial intervention program was evaluated. 76 parents filled out an
      questionnaire about the utilization and efficiency of different parts of the
      program. The results show that the efficiency of the intervention program is very
      high. Nationality of the families, socioeconomic status und the presence of a
      relapse of the cancer were the most important predictors of taking part in the
      different parts of the program. Parents reported that the most positive effects
      of the psychosocial intervention program consisted in a gain of information and a
      better intrafamiliar communication. In conclusion the evaluation showed a high
      acceptance of the family-oriented psychosocial intervention program and positive
      effects on the whole family.

PMID- 10087896
TI  - [Abbreviated Psychopathological Scale in basic documentation in child and
      adolescent psychiatry--results of a multicenter study].
AB  - The short form of the Clinical Assessment Scale of Child and Adolescent
      Psychopathology (CASCAP) assesses psychopathological features only on the level
      of symptom domains and not on the level of single symptoms. The instrument is
      part of the basic documentation of child and adolescent psychiatry. Based on the
      multicenter study sample of CASCAP the ratings of the symptom domains in the
      different centers were analysed. Inpatients receive higher ratings than
      outpatients on nearly all symptom domains. Only minor differences could be found
      between the centres. Advantages and disadvantages of this short version are
      discussed.

PMID- 10087897
TI  - [The desire for attachment with the culture of origin--migrant families in
      psychodynamic therapy].
AB  - The way migration is worked through will be largely influenced by two aspects:
      the wish for continuity in the personal identity one had build up before
      migrating, as well as the longing for staying interwoven with the social group
      and the cultural life world one had left. Only when these wishes for continuity
      and interwovenness are safeguarded, the loss that migration also has become, can
      be experienced and mourned. The element of discontinuity inherent in the
      migration process, then becomes less threatening. Thereby, aspects of "new
      encountered culture" will become woven into "brought with culture". To describe
      this process of intercultural encounter in a migrant family, Winnicott's concept
      of "potential space" or "transitional space" proves to be very apt. We illustrate
      this with a clinical vignette of a Moroccan family wherein adolescence brings
      about intergenerational conflicts, shaped by as well as influencing cultural
      identities. This article references to some earlier work of Lanfranchi (1988,
      1993) and of Lanfranchi and Molinari (1995) in this journal.

PMID- 10087898
TI  - [Developmentally encouraging relations--transfer of psychotherapeutic concepts
      and methods to pedagogic healing of learning disabled and mentally handicapped
      children].
AB  - The authors how the possibility of integrating psychotherapeutic methods into the
      therapeutic pedagogical work day by describing the therapy progress of a slightly
      mentally handicapped boy who suffered under a narcissistic disorder with
      depressive parts. In this process the authors oriented themselves primarily on
      depth psychology and client-centered play therapy but also included therapeutic
      elements. The counselling accompanying the therapy ensures integration into
      everyday life. On this basis it is possible to reduce the boy's overdimensional
      self and to build up object constancy. In conclusion, it is shown how individual
      therapeutic interventions can be integrated additionally into the pedagogical day
      to-day life.

PMID- 10087899
TI  - Computer aided design and fabrication of models for in vitro studies of vascular
      fluid dynamics.
AB  - An integrated computer aided design/computer aided manufacture system has been
      used to model the complex geometry of blood vessel anastomoses. Computer models
      are first constructed with key dimensions derived from radiological images of
      bypass grafts, and from casts of actual blood vessel anastomoses. Physical models
      are then fabricated in one of two ways: the surface geometry data can be used to
      control the movement of a three-axis milling machine; alternatively, the same
      data can be exported in a form that can be interpreted by a stereolithography
      apparatus. Both methods produce geometrically defined solid investments that can
      be used in a multistep casting process that yields high-quality physical models
      for vascular fluid dynamic studies. This technique is useful for parametric
      studies.

PMID- 10087900
TI  - Effect of phospholipidic boundary lubrication in rigid and compliant
      hemiarthroplasty models.
AB  - Hemiarthroplasty may benefit from materials which produce lower friction and
      improved boundary lubrication protection during start-up conditions. The purpose
      of this study was to evaluate the effect of phospholipidic boundary lubrication
      in both rigid and compliant hemiarthroplasty. An in vitro model was designed to
      dissociate the relative contribution of implant material compliance and the
      presence of phospholipid to the overall friction of a hemiarthroplasty contact
      using bovine articular cartilage. Normal bovine articular cartilage was
      articulated against four flat materials using reciprocating motion: (a)
      borosilicate glass: (b) borosilicate glass coated with
      dipalmitoylphosphatidylcholine (DPPC); (c) polyurethane (PU) elastomer (Tecoflex
      SG93A, a medical-grade aliphatic thermoplastic PU, Thermedics Incorporated.
      Woburn, Massachusetts); and (d) surface-coated PU (Tecoflex SG93A substrate
      coated with lipid-attracting copolymer poly[methacryloyloxyethyl
      phosphorylcholine (MPC)-co-butyl methacrylate (BMA)]. Tests were conducted in
      physiologically simulated tribological conditions for a non-conformal point
      contact. Friction and lubrication analysis was performed using both static and
      kinetic coefficients of friction mu measured for each group as a function of time
      for a sliding distance of up to 60 m. Results showed that the inclusion of
      supplemental phospholipid, DPPC, on a rigid substrate significantly decreased mu
      in comparison with the control (cartilage-glass). Additionally, removal of
      phospholipid components from the articular cartilage surface produced a
      significantly greater start-up mu in comparison with normal cartilage at the test
      onset. The use of a material with a lower modulus resulted in lower mu for the
      entire duration of the test. Polyurethane elastomer coated with the lipid
      attracting copolymer, poly(MPC-co-BMA), resulted in the lowest frictional
      response. As seen in this study, the improvement of low-modulus hemiarthroplasty
      may involve the optimization of chemical modification and incorporation of lipid
      attracting MPC copolymers onto compliant materials. However, further tests are
      warranted to determine whether lipid-attracting MPC copolymers perform as well
      during long-time, in vivo wear studies.

PMID- 10087901
TI  - The effect of cartilage deformation on the laxity of the knee joint.
AB  - In this paper, deformation of the articular cartilage layers is incorporated into
      an existing two-dimensional quasi-static model of the knee joint. The new model
      relates the applied force and the joint displacement, as measured in the Lachmann
      drawer test, and allows the effect of cartilage deformation on the knee joint
      laxity to be determined. The new model augments the previous knee model by
      calculating the tibio-femoral contact force subject to an approximate 'thin
      layer' constitutive equation, and a method is described for finding the
      configuration of the knee under a specified load, in terms of a displacement from
      a zero-load reference configuration. The results show that inclusion of
      deformable cartilage layers can cause a reduction of between 10 and 35 per cent
      in the force required to produce a given tibial displacement, over the range of
      flexion angles considered. The presence of cartilage deformation was found to be
      an important modifier of the loading response but is secondary to the effect of
      ligamentous extension. The flexion angle dependence of passive joint laxity is
      much more strongly influenced by fibre recruitment in the ligaments than by
      cartilage deformation.

PMID- 10087902
TI  - Press-fit acetabular cup fixation: principles and testing.
AB  - Pre-clinical testing of the fixation of press-fit acetabular components of total
      hip prostheses relies on cadaver or synthetic bone, but the properties and
      geometry of bone models differ from those of physiological bone. Cup designs use
      varied mechanisms for initial stability in bone; therefore, using different
      analogues and tests is appropriate. Press-fit cup stability was tested in the
      following: firstly, polyurethane (PU) foam modelling cancellous support;
      secondly, glass-fibre reinforced epoxide (GFRE) tubes modelling acetabular
      cortical support; thirdly, cadaveric acetabula. Three commercial cups [Harris
      Galante II (H-G-II), Zimmer; Optifix, Smith & Nephew, Richards; porous coated
      anatomic (PCA), Howmedica] and an experimental cup with enhanced rim fixation
      were tested in three modes: direct pull-out, lever-out and axial torque. The
      fixation stabilities measured in the PU and the GFRE models showed trends
      consistent with those in cadaver bone, differing in the oversizing and cup
      geometry. The experimental cup was significantly more secure in most modes than
      other cups; the H-G II and Optifix cups showed similar stabilities, lower than
      that of the experimental cup but greater than that of the PCA cup (analysis of
      variance and Tukey's highly significant test; p < 0.001). The stabilities
      measured in cadaver bone more closely approximated those in GFRE. The use of
      several bone analogues enables separation of fixation mechanisms, allowing more
      accurate prediction of in vivo performance.

PMID- 10087903
TI  - Non-destructive and non-invasive observation of friction and wear of human joints
      and of fracture initiation by acoustic emission.
AB  - Quality control in orthopaedic diagnostics according to DIN EN ISO 9000ff
      requires methods of non-destructive process control, which do not harm the
      patient by radiation or by invasive examinations. To obtain an improvement in
      health economy, quality-controlled and non-destructive measurements have to be
      introduced into the diagnostics and therapy of human joints and bones. A non
      invasive evaluation of the state of wear of human joints and of the cracking
      tendency of bones is, as of today's point of knowledge, not established. The
      analysis of acoustic emission signals allows the prediction of bone rupture far
      below the fracture load. The evaluation of dry and wet bone samples revealed that
      it is possible to conclude from crack initiation to the bone strength and thus to
      predict the probability of bone rupture.

PMID- 10087904
TI  - Three-dimensional surface characterization for orthopaedic joint prostheses.
AB  - This study attempts to investigate a range of 'better' methods for the
      characterization of the three-dimensional (3D) surface topography of orthopaedic
      joint prostheses. In this paper, a new characterization tool for the
      comprehensive identification and evaluation of functional features of these
      surface topographies is presented. For identification, the surface topography is
      investigated in a space-scale space, by employing wavelet analysis. The
      roughness, waviness and form involved in surface topography are consequently
      separated and recovered respectively. The multiscalar topographical features are
      identified and captured. The errors caused as a consequence of three-dimensional
      measurement methods can be reduced. After identification, the three-dimensional
      surface assessment techniques previously reported by Stout and co-workers are
      used for the quantitative evaluation of various surface roughness features of the
      orthopaedic joint prostheses. Moreover, the functional properties, such as
      bearing area, material volume and void volume which are significantly effected by
      large peaks, pits and scratches are studied and the location of isolated peaks,
      pits and scratches in the different scales is also clearly characterized. In this
      work, measurement of the femoral heads and acetabular cups is carried out to
      demonstrate the applicability of the characterization technique for the three
      dimensional surface topography of orthopaedic joint prostheses.

PMID- 10087905
TI  - On-line computer system to minimize laser injuries during surgery: preliminary
      system layout and proposal of the key features.
AB  - The aim of this paper is to investigate some new user interface ideas and related
      application packages which aim to improve the degree of safety in an operating
      room during surgical operations in which an invasive laser beam is deployed. The
      overall value of the proposition is that a means is provided which ensures the
      successful completion of the surgical case while minimizing the risk of thermal
      and mechanical injuries to healthy tissues adjacent to the surgical field.
      According to surgeons operating with a variety of CO2 lasers available at both
      the National Cancer Institute in Milan, Italy, and the Sackler School of
      Medicine, Tel Aviv University, Israel, each laser device presents different
      cutting and coagulation properties. In order to identify which 'ideal' procedure
      might corroborate the subjective impression of each surgeon and also to provide
      one common tool to ensure procedures with a high level of safety, the author has
      worked for several months with surgeons and technicians of both Institutions to
      define the general design of a new on-line surgical operation planning and design
      system to be used during the pre-operative briefing activities and also as a
      consultation tool during operation. This software package will be developed and
      tested on both 'C' and FORTRAN compilers running on a commercially available PC
      which is driving a continuous wave (CW) CO2 laser device via its Instrument Bus
      interface. The present proposal describes the details of a software package
      called LCA (Laser-beam Controller and Adviser) which performs several controls in
      parallel on the key output parameters of a laser beam device during its
      utilization in delicate surgical operations. The required performances of this
      device needed during a given surgical operation are pre-simulated and compared
      against the well-known safety limits, which are stored in the computer's mass
      storage. If the surgeon's decision about the laser device set-up are considered
      to be too close to the required physiological safety limits, then the SW alerts
      the surgeon and proposes alternatives based on other combinations of both HW and
      SW configurations. An additional application of LCA uses this SW as a warning
      tool during the operation itself. If a wrong set-up of the laser device is
      accidentally used, an alarm will be generated and the laser beam automatically
      switched-off prior to an 'incident report' printout. The operation will continue
      only when the surgeon validates the choices that the SW suggests for
      implementation. If necessary, the surgeon can switch off the device and continue
      to operate it manually. In this case, the surveillance mode will be totally
      excluded.

PMID- 10087906
TI  - Signal transduction and regulation in smooth muscle: problems and progress.

PMID- 10087907
TI  - Applicability of the sliding filament/crossbridge paradigm to smooth muscle.

PMID- 10087908
TI  - Regulation of cross-bridge cycling by Ca2+ in smooth muscle.

PMID- 10087909
TI  - Calcium permeant ion channels in smooth muscle.

PMID- 10087910
TI  - Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and
      phosphatases.
AB  - The concept of pharmacomechanical coupling, introduced 30 years ago to account
      for physiological mechanisms that can regulate contraction of smooth muscle
      independently of the membrane potential, has since been transformed from a
      definition into what we now recognize as a complex of well-defined, molecular
      mechanisms. The release of Ca2+ from the SR by a chemical messenger, InsP3, is
      well known to be initiated not by depolarization, but by agonist-receptor
      interaction. Furthermore, this G-protein-coupled phosphatidylinositol cascade,
      one of many processes covered by the umbrella of pharmacomechanical coupling, is
      part of complex and general signal transduction mechanisms also operating in many
      non-muscle cells of diverse organisms. It is also clear that, although the major
      contractile regulatory mechanism of smooth muscle,
      phosphorylation/dephosphorylation of MLC20, is [Ca2+]-dependent, the activity of
      both the kinase and the phosphatase can also be modulated independently of
      [Ca2+]i. Sensitization to Ca2+ is attributed to inhibition of SMPP-1M, a process
      most likely dominated by activation of the monomeric GTP-binding protein RhoA
      that, in turn, activates Rho-kinase that phosphorylates the regulatory subunit of
      SMPP-1M and inhibits its myosin phosphatase activity. It is likely that the tonic
      phase of contraction activated by a variety of excitatory agonists is, at least
      in part, mediated by this Ca(2+)-sensitizing mechanism. Desensitization to Ca2+
      can occur either through inhibitory phosphorylation of MLCK by other kinases or
      autophosphorylation and by activation of SMPP-1M by cyclic nucleotide-activated
      kinases, probably involving phosphorylation of a phosphatase activator. Based on
      our current understanding of the complexity of the many cross-talking signal
      transduction mechanisms that operate in cells, it is likely that, in the future,
      our current concepts will be refined, additional mechanisms of pharmacomechanical
      coupling will be recognized, and those contributing to the pathologenesis
      diseases, such as hypertension and asthma, will be identified.

PMID- 10087911
TI  - Molecular and cellular phenotypes and their regulation in smooth muscle.

PMID- 10087912
TI  - Prodomains--adaptors--oligomerization: the pursuit of caspase activation in
      apoptosis.

PMID- 10087913
TI  - The location of the linker histone on the nucleosome.

PMID- 10087914
TI  - Moonlighting proteins.
AB  - The idea of one gene--one protein--one function has become too simple because
      increasing numbers of proteins are found to have two or more different functions.
      The multiple functions of such moonlighting proteins add another dimension to
      cellular complexity and benefit cells in several ways. However, cells have had to
      develop sophisticated mechanisms for switching between the distinct functions of
      these proteins.

PMID- 10087915
TI  - Integrin alpha- and beta 4-subunit-domain homologues in cyanobacterial proteins.

PMID- 10087916
TI  - A novel family of DNA-polymerase-associated B subunits.

PMID- 10087917
TI  - Protein translocation into and across the bacterial plasma membrane and the plant
      thylakoid membrane.
AB  - Over the past decade, some familiar themes have emerged on how proteins are
      inserted into or translocated across the plant chloroplast thylakoid membrane and
      bacterial inner membranes. In the SecA and signal recognition particle (SRP)
      pathways, nucleotides and soluble factors are used to translocate proteins across
      the membrane bilayer in the unfolded state. However, the delta pH-dependent
      pathway in thylakoids uses a radically different mechanism: transport of proteins
      across the membrane is driven by the transmembrane pH gradient, and neither
      stromal factors nor nucleotide triphosphates are needed. In addition, this
      pathway, which requires the membrane-bound protein Hcf106, appears to translocate
      proteins in a tightly folded form. Recently, a similar pathway has been shown to
      operate in eubacteria, and several of its components have been identified.

PMID- 10087918
TI  - Dealing with energy demand: the AMP-activated protein kinase.
AB  - The AMP-activated protein kinase (AMPK) is a member of a metabolite-sensing
      protein kinase family that is found in all eukaryotes. AMPK activity is regulated
      by vigorous exercise, nutrient starvation and ischemia/hypoxia, and modulates
      many aspects of mammalian cell metabolism. The AMPK yeast homolog, Snf1p, plays a
      major role in adaption to glucose deprivation. In mammals, AMPK also has diverse
      roles that extend from energy metabolism through to transcriptional control.

PMID- 10087919
TI  - Is protein folding hierarchic? I. Local structure and peptide folding.
AB  - The folding reactions of some small proteins show clear evidence of a hierarchic
      process, whereas others, lacking detectable intermediates, do not. Nevertheless,
      we argue that both classes fold hierarchically and that folding begins locally.
      If this is the case, then the secondary structure of a protein is determined
      largely by local sequence information. Experimental data and theoretical
      considerations support this argument. Part I of this article reviews the
      relationship between secondary structures in proteins and their counterparts in
      peptides.

PMID- 10087920
TI  - PSORT: a program for detecting sorting signals in proteins and predicting their
      subcellular localization.

PMID- 10087921
TI  - The elusive branch-point compound of aromatic amino acid biosynthesis.

PMID- 10087922
TI  - WNT targets. Repression and activation.
AB  - Several puzzling observations made previously suggested that target genes that
      are activated by WNT signaling during development were actively repressed in the
      absence of the signal. Recent work sheds light on how this switch between
      repression and activation is regulated.

PMID- 10087923
TI  - TGF beta inhibitors. New and unexpected requirements in vertebrate development.
AB  - Analysis of embryonic induction has pointed to the importance of the antagonistic
      roles played by secreted inducing factors and their soluble inhibitory binding
      proteins. These interactions have been particularly well characterized in
      patterning the primary axes of insects and vertebrates. New results implicate
      similar antagonistic relationships in numerous later events of embryogenesis.

PMID- 10087924
TI  - From complex traits to complex alleles.
AB  - Several recent studies using natural populations of Drosophila show that one must
      be very careful when sorting among the large number of molecular polymorphisms
      found at most loci to identify the nucleotide changes responsible for phenotypic
      variation in complex traits. Indeed, several mutations within a single allele can
      interact to generate the overall observed effect. The results are instructive
      both for those interested in the genetics of evolutionary change and for those
      attempting to ferret out the genetic basis of complex human diseases.

PMID- 10087925
TI  - Bioinformatics in Siberia. First International Conference on Bioinformatics of
      Genome Regulation and Structure, Novosibirsk, Siberia, Russia, 24-27 August 1998.

PMID- 10087926
TI  - Gene regulation and cancer. Gene regulation and cancer: 10th anniversary meeting
      of the American Association of Cancer Research Special Conferences in Cancer
      Research, the Homestead, Hot Springs, Virginia, USA, 14-18 October 1998.

PMID- 10087927
TI  - Do unintended antisense transcripts contribute to sense cosuppression in plants?

PMID- 10087928
TI  - Taking the plunge. Terminal differentiation in Dictyostelium.
AB  - During the last stage of Dictyostelium development a motile, cylindrical slug
      transforms into an immotile, stalked fruiting body and the constituent cells
      change from amoebae to either refractile spores or vacuolated stalk cells.
      Analysis of this process using genetics and simple culture techniques is becoming
      a powerful way of investigating a number of conserved signal transduction
      processes. A common pathway activating cAMP-dependent protein kinase (PKA)
      triggers the maturation of spore cells and those stalk cells forming the stalk.
      It uses a eukaryotic version of the 'bacterial' two-component phospho-relay
      system to control cAMP breakdown. A second pathway, inhibiting the GSK3 protein
      kinase, might control the maturation of a distinct set of stalk cells at the base
      of the fruiting body.

PMID- 10087929
TI  - Neural induction. A bird's eye view.
AB  - Since the discovery of the phenomenon of neural induction by Spemann and Mangold
      in 1924, considerable effort has been invested in identifying the signals
      produced by the organizer that are responsible for diverting the fate of cells
      from epidermal to neural. Substantial progress has been made only recently by the
      finding in amphibians that BMP4 is a neural inhibitor and epidermal inducer, and
      that endogenous antagonists of BMPs are secreted by the organizer. However,
      recent results in the chick point to the existence of other, upstream events
      required before BMP inhibition stabilizes neural fates. Here we take a critical
      view of the evidence for and against the view that BMP inhibition is a sufficient
      trigger for neural induction in different vertebrates.

PMID- 10087930
TI  - mRNA degradation. A tale of poly(A) and multiprotein machines.
AB  - The Escherichia coli RNA degradosome is a multiprotein complex containing an
      endoribonuclease, polynucleotide phosphorylase and a DEAD-box RNA helicase. A
      related complex has been described in the spinach chloroplast. The exosome and
      the mtEXO complex have recently been described in yeast and it is likely that
      related complexes also exist in animal cells. This research suggests the
      widespread existence of sophisticated machines for the efficient degradation of
      messenger RNA. The DEAD-box helicase in the degradosome can unwind regions of RNA
      structure that interfere with 3'-5' degradation. The polyadenylation of RNA 3'
      ends is also known to promote degradation by creating a 'toehold' for the
      degradation machinery. Much remains to be learned about the regulation of mRNA
      stability. The complexity of the degradation process, both in the eubacteria and
      in the eukaryotes, suggests that many steps are possible points of control.

PMID- 10087931
TI  - Feasting, fasting and fermenting. Glucose sensing in yeast and other cells.
AB  - Glucose is the primary fuel for most cells. Because the amount of available
      glucose can fluctuate wildly, organisms must sense the amount available to them
      and respond appropriately. Altering gene expression is one of the major effects
      glucose has on cells. Two different glucose sensing and signal transduction
      pathways in the yeast S. cerevisiae--one for repression, and one for induction of
      gene expression--have recently come into focus. What we have learned about these
      glucose sensing and signaling mechanisms might shed light on how other cells
      sense and respond to glucose.

PMID- 10087932
TI  - The DNA methylation paradox.
AB  - The methylation of CpG islands is often equated with transcriptional inactivity
      and there is overwhelming evidence that this is the case for islands located in
      gene promoters. Such methylation is probably part of a mechanism to permanently
      silence the activities of genes, including those on the inactive X chromosome.
      Not all CpG islands and methylation sites are located in known promoters; several
      tissue-specific and imprinted genes have CpG islands located at considerable
      distances downstream of transcription initiation sites, and many genes have
      multiple promoters. Methylation of CpG islands downstream of transcription
      initiation does not block elongation in mammalian cells. This has given rise to
      an interesting paradox in which methylation in the transcribed region is often
      correlated with expression, in contrast to the inverse correlation seen at the
      site of transcriptional initiation. The methylation paradox might be resolved if
      it is hypothesized that transcription through a CpG island facilitates de novo
      methylation.

PMID- 10087933
TI  - The Genome Channel: a browser to a uniform first-pass annotation of genomic DNA.

PMID- 10087934
TI  - Stimulus generalization, context change, and forgetting.
AB  - Forgetting is often attributed to retrieval failure caused by background
      contextual cues changing over time. However, generalization between stimuli may
      increase over time and make them increasingly interchangeable. If this effect
      occurs with contextual cues, it might cancel any effect of a changing context.
      The authors review the evidence and suggest a resolution of this paradox.
      Although generalization gradients can change over time, the effect is not always
      strong. Increased responding to nontarget stimuli is not often shown, and few
      studies have demonstrated such changes with contextual cues in a way that rules
      out other interpretations. Even this example of forgetting may be caused by
      retrieval failure. The physical contexts manipulated in learning and memory
      experiments themselves occur within a superordinate temporal context and can thus
      be forgotten with no inherent challenge to a context-change account of
      forgetting.

PMID- 10087935
TI  - The contextual change paradox is still unresolved: comment on Bouton, Nelson, and
      Rosas (1999)
AB  - According to the contextual change theory of memory loss, spontaneous forgetting
      reflects a retrieval impairment due to subtle and unprogrammed shifts in
      environmental cues over a retention interval. However, Riccio, Richardson, and
      Ebner (1984) noted an apparent paradox in this model; specifically, laboratory
      studies inducing explicit shifts in contextual cues found less disruption of
      performance as retention intervals increased. Bouton, Nelson, and Rosas (1999)
      critiqued several of the claims made by Riccio et al. and concluded that the
      contextual cue theory is still a valid account of spontaneous forgetting. In this
      comment, the authors address the 3 major criticisms offered by Bouton et al.,
      point out an inconsistency in their argument, and conclude that the original
      paradox still poses problems for the contextual change theory of forgetting.

PMID- 10087936
TI  - Cognitive integration of language and memory in bilinguals: semantic
      representation.
AB  - Understanding cognitive research on the integration of 2 languages in bilingual
      memory is difficult because of the different terminology, methodology, analysis,
      and interpretation strategies that scholars with different backgrounds bring to
      the research. These studies can be usefully categorized on 2 dimensions: memory
      for verbal experience versus linguistic knowledge, and systemwise versus pairwise
      issues. Experimental findings in this area converge on the conclusion that at the
      word meaning/conceptual level, both episodic and linguistic memory can be
      characterized as shared at the systems level and at least partly shared at the
      pairwise translation-equivalent level. Interpretation problems that stem from
      weak hypothesis testing structure and from covert translation can be minimized by
      using appropriate design and analysis techniques.

PMID- 10087937
TI  - Enduring and different: a meta-analysis of the similarity in parents' child
      rearing.
AB  - The assessment of child-rearing beliefs and behavior has predominantly focused on
      qualities and characteristics believed to reflect consistent, enduring qualities
      of parenting--the similarity in child rearing. This review evaluates the evidence
      for similarity and differences among 3 types of child-rearing data and includes
      comparisons across time, children, and situations. Both relative stability and
      mean level differences were found in all 3 domains. The most similarity was found
      in the across-time and across-children domains, although it depended on the child
      rearing construct and methodology used. It is argued that attention to the
      variability and change in child rearing must be incorporated into theoretical
      models of parenting to better understand the nature of child rearing and, in
      turn, parental influence on children's development.

PMID- 10087938
TI  - Accounting for the effects of accountability.
AB  - This article reviews the now extensive research literature addressing the impact
      of accountability on a wide range of social judgments and choices. It focuses on
      4 issues: (a) What impact do various accountability ground rules have on
      thoughts, feelings, and action? (b) Under what conditions will accountability
      attenuate, have no effect on, or amplify cognitive biases? (c) Does
      accountability alter how people think or merely what people say they think? and
      (d) What goals do accountable decision makers seek to achieve? In addition, this
      review explores the broader implications of accountability research. It
      highlights the utility of treating thought as a process of internalized dialogue;
      the importance of documenting social and institutional boundary conditions on
      putative cognitive biases; and the potential to craft empirical answers to such
      applied problems as how to structure accountability relationships in
      organizations.

PMID- 10087939
TI  - An update on DNA-based BRCA1/BRCA2 genetic counseling in hereditary breast
      cancer.
AB  - The identification of BRCA1 and BRCA2 mutations has enabled physicians to
      identify persons at high risk for carcinoma of the breast and ovary in hereditary
      breast-ovarian cancer (HBOC) families. Many physicians have limited knowledge
      about the effective translation of these new discoveries into clinical practice
      settings. This problem is further confounded by the limited number of genetic
      counselors who have experience with cancer genetics. Genetic counseling about DNA
      test results was provided to 420 patients from 37 HBC/HBOC families. Descriptive
      data were collected and recorded about their responses to questions posed
      immediately before and after test results were disclosed. Findings disclosed a
      significant tendency of patients to overestimate rather than underestimate their
      risk (P < .001) prior to receiving results. The chief reason for declining to
      receive results was fear of insurance discrimination. The primary reason that
      patients sought test results was for their children. Most women reported that, if
      testing identified them as mutation carriers, they would consider lifetime
      surveillance and prophylactic surgery. Responses to DNA test results were varied
      and often unpredictable. Counseling by an appropriately educated and skilled
      professional is essential to assist people in making decisions regarding testing
      and health management.

PMID- 10087940
TI  - Fluorescence in situ hybridization analysis shows the frequent occurrence of
      14q32.3 rearrangements with involvement of immunoglobulin switch regions in
      myeloma cell lines.
AB  - In many B-cell malignancies, 14q32.3 chromosomal rearrangements involving the
      immunoglobulin heavy chain (IgH) locus have been shown to be pathognomonic for
      the disease. Although in myeloma heterogeneous and complex karyotypes are found,
      14q32.3 translocations are prominent. However, owing to the telomeric position of
      the IgH locus, 14q32.3 translocations may be easily missed. We established
      fluorescence in situ hybridization (FISH) assays on chromosomes and DNA fibers to
      determine both the occurrence of 14q32.3 rearrangements in myeloma cell lines and
      the precise localization of the breakpoints in the IgH locus. Our results show
      that 14q32.3 chromosomal rearrangements are present in almost every myeloma cell
      line analyzed (17 of 19, 89%). Breakpoint analysis of the lines harboring one or
      more 14q32.3 rearrangements with the use of fiber-FISH revealed the involvement
      of switch regions in the IgH locus in 11 of 17 cell lines. Remarkably,
      pseudogamma genes without switch regions were involved in 3 of 17 cell lines, all
      derived from IgA myelomas. Three of 17 cell lines contained breakpoints outside a
      switch or immunoglobulin heavy chain constant region. The almost ubiquitous
      presence of 14q32.3 rearrangements suggests an obligatory role in the development
      of myeloma. The high incidence of breakpoints involving switch regions indicates
      an oncogenic event in a late stage of B-cell differentiation.

PMID- 10087941
TI  - Cumulation of TP53 mutations and p16INK4A/p15INK4B homozygous deletions in human
      papilloma virus type 16 positive scrotal cancer.
AB  - Scrotal cancer is the first described occupational cancer. The frequency of
      occupation-related scrotal cancer is very rare because of better hygiene and
      protective clothing. Human papilloma viruses (oncogenic types 16 and 18) were
      reported as the causative agents in the pathogenesis of scrotal cancers. E5, E6,
      and E7 proteins, expressed by human papilloma virus type 16, affect the cell
      cycle at the G1 checkpoint. TP53, p16INK4A, and p15INK4B were reported as the
      transcription factors that regulate the cell cycle on the same pathway. Here, the
      mutation pattern of TP53, p16INK4A, and p15INK4B genes and the homo/hemizygous
      deletion patterns of p16INK4A/p15INK4B genes are presented in four scrotal
      carcinoma cases. The results were correlated with the findings of oncogenic human
      papilloma viruses (types 16 and 18) in this panel. In two of four case, human
      papilloma virus type 16 was observed. Homozygous deletion in p16INK4A/p15INK4B
      genes and a codon 259 missense point mutation (GAC-->TAC; Asp-->Tyr) in the TP53
      gene were observed in one human papilloma positive scrotal carcinoma case. The
      homozygous deletion in p16INK4A/p15INK4B genes was observed in another human
      papilloma positive scrotal carcinoma case. The cumulation of TP53 mutations and
      p16INK4A/p15INK4B homozygous deletions in human papilloma virus type 16 positive
      scrotal carcinoma cases indicate that the alterations of TP53, p16INK4A, and
      p15INK4B genes have an important role in the progression of scrotal cancers, as
      well as other factors. The survival rate for the two human papilloma virus type
      16 positive patients who had a TP53 mutation or p16INK4A/p15INK4B homozygous
      deletion or both was lower than that for the human papilloma virus type 16
      negative cases who had no TP53, p16INK4A, and p15INK4B mutation. The molecular
      alteration of TP53, p16INK4A, and p15INK4B genes may be useful as a prognostic
      marker in scrotal cancer.

PMID- 10087942
TI  - Involvement of chromosome losses in the progression and metastasis formation of a
      human malignant melanoma.
AB  - To characterize the possible cytogenetic link between a primary tumor and its
      metastasis, interphase cytogenetic analysis was performed on tumor cells and
      cutaneous metastasis from a male patient with malignant melanoma by using
      fluorescence in situ hybridization. The numbers of distinct hybridization domains
      specific for ten different pericentromeric sequences were used as indicators of
      copy numbers of these chromosomes. In the primary tumor, the majority of cells
      had two copies of these chromosomes, but significant numbers of nuclei also were
      present with one and three copies. In addition, in almost all cells, both sex
      chromosomes were abnormal; nullisomy of the Y chromosome was associated with X
      disomy. The corresponding metastatic tumor cells were predominantly monosomic;
      only the distribution of chromosomes 11 and 7 was similar to the primary tumor.
      In the metastatic tumor, the sex chromosomes had a normal copy number; that is,
      one Y and one X were detected. These data indicate that both the initiation and
      the progression of this melanoma are associated with chromosome losses.

PMID- 10087943
TI  - Ring chromosomes in a malignant mesenchymoma.
AB  - We report, for the first time, the cytogenetic and molecular genetic constitution
      of a human mesenchymoma. As in several other soft tissue sarcomas, supernumerary
      ring and rod-shaped marker chromosomes were observed next to an otherwise normal
      diploid karyotype. Comparative genomic in situ hybridization and whole chromosome
      painting experiments revealed that chromosome 1q21-q25 and 12q14-q15 sequences
      were amplified, and that these sequences resided on the supernumerary marker
      chromosomes. We assume that, in this malignant mesenchymoma, the observed
      chromosomal anomalies may be associated with its well differentiated
      liposarcomatous component.

PMID- 10087944
TI  - MYC amplification in two further cases of acute myeloid leukemia with trisomy 4
      and double minute chromosomes.
AB  - We report two cases of trisomy 4 with double minute chromosomes (dmin): one in a
      woman with acute myeloid leukemia (AML), French-American-British subtype M2, the
      other in a man with chronic myelomonocytic leukemia. In the former case, many
      cells without trisomy 4 but with dmin were present, a finding not observed in
      previously reported cases. In both cases, fluorescence in situ hybridization
      studies demonstrated the double minutes to be MYC amplicons. Ten cases of AML
      with trisomy 4 and dmin have now been described; in the five cases investigated,
      the dmin have been shown to be amplified MYC gene sequences.

PMID- 10087945
TI  - Neuroblastoma in two siblings supports the role of 1p36 deletion in tumor
      development.
AB  - Familial neuroblastoma occurs rarely. We studied a family with three children;
      one of them has a disseminated (stage 4) and another has a localized (stage 2)
      neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors
      by using double-color fluorescence in situ hybridization. The MYNC gene was found
      in single copy in both tumors. Loss of heterozygosity (LOH) and restriction
      fragment length polymorphism analyses were performed by using DNA from frozen
      tumor cells and from microdissected tumor areas excised from paraffin-embedded
      sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell
      population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the
      stage-4 patient were diploid and showed allelic loss at the following loci:
      D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study
      showed that the siblings inherited the same paternal 1p36-->pter chromosome
      region by homologous recombination and that, in the two tumors, arm 1p of
      different chromosomes of maternal origin was damaged. Our results suggest that
      the siblings inherited the predisposition to neuroblastoma associated with
      paternal 1p36 region and that tumors developed as a consequence of somatic loss
      of the maternal 1p36 allele.

PMID- 10087946
TI  - Trisomy 22 in acute myeloid leukemia: a marker for myeloid leukemia with
      monocytic features and cytogenetically cryptic inversion 16.
AB  - Trisomy 22 is an uncommon chromosomal abnormality in acute myeloid leukemia.
      Recent studies, however, have shown an association between trisomy 22 and acute
      myeloid leukemia with a monocytic component, and in particular, acute
      myelomonocytic leukemia with marrow eosinophilia. Furthermore, it has also been
      suggested that trisomy 22 was in fact only a secondary chromosomal change
      occurring in acute myeloid leukemia with inv(16). In this report, we analyze the
      morphological, cytogenetic, and molecular findings of three cases of acute
      myeloid leukemia with trisomy 22 but without cytogenetic evidence of inv(16). The
      results indicate a consistent association between trisomy 22 and inv(16), the
      latter being cytogenetically cryptic in some cases. This finding is of potential
      diagnostic and therapeutic significance.

PMID- 10087947
TI  - PHA/IL2: an efficient mitogen cocktail for cytogenetic studies of non-Hodgkin
      lymphoma and chronic lymphocytic leukemia.
AB  - This study documents the utility of a mitogen/cytokine cocktail composed of
      phytohemagglutinin and Interleukin 2 (PHA/IL2) used to stimulate cultures from
      patients with chronic lymphoproliferative disorders. We report the results of a
      selected series of 57 patients with non-Hodgkin lymphoma (NHL) or chronic
      lymphocytic leukemia (CLL), in which only the culture stimulated with PHA/IL2
      demonstrated the presence of an abnormal clone. On average, cells in the abnormal
      clone comprised 40% of the mitotic cells in this culture. The most common
      abnormalities observed in these patients were trisomy 12, present in 39% of the
      cases, and t(14;18), seen in 14% of cases.

PMID- 10087948
TI  - Premature centromere division in patients with multiple endocrine neoplasia type
      1.
AB  - Frequency of mitoses with premature centromere division (PCD) was examined in
      lymphocytes from subjects with multiple endocrine neoplasia type 1 (MEN 1). An
      increase in PCD after exposure to an alkylating agent was observed in subjects
      with MEN 1 who carry a heterozygous MEN1 gene mutation but not in normal controls
      or in affected subjects without the MEN1 gene mutation. These findings support
      the inclusion of MEN 1 as a chromosome instability syndrome and recognition of
      PCD as a manifestation of chromosome instability. Furthermore, these results
      suggest that the MEN1 gene product may function to maintain the integrity of DNA.

PMID- 10087949
TI  - Development of acute promyelocytic leukemia with isochromosome 17q after BCR/ABL
      positive chronic myeloid leukemia.
AB  - We describe a pediatric case of acute promyelocytic leukemia with an i(17q) after
      treatment of BCR/ABL positive chronic myeloid leukemia (CML) for 3.5 years. The
      patient was treated with Busulphan, alpha-2a interferon, hydroxyurea, and
      cytosine arabinoside at various times in the course of the chronic phase of CML,
      because he had no HLA-identical donor for bone marrow transplantation.
      Hematologic remission was achieved for a short time, but cytogenetic remission
      was never possible. When promyelocytic blast crisis was diagnosed according to
      the French-American-British classification, cytogenetic studies revealed an
      i(17q) as a new feature in our patient. The promyelocytic transformation was
      associated with the appearance of an i(17q) preceding CML are discussed in the
      light of recent literature.

PMID- 10087950
TI  - Jumping translocations involving chromosome 1q in a patient with Crohn disease
      and acute monocytic leukemia: a review of the literature on jumping
      translocations in hematological malignancies and Crohn disease.
AB  - A 36-year-old man with a 10-year history of Crohn disease (CD) presented with
      gross hematuria and blasts in his peripheral blood. A chromosome analysis
      revealed one normal cell and 33 abnormal cells. The stem line was 47,XY,+8. The
      multiple side lines also had a jumping translocation between chromosome 1q31-32
      and 4, 8, 10, 17, and 18 terminal regions. A cytogenetic, morphologic, and
      immunophenotypic analysis of a bone marrow aspirate and biopsy demonstrated acute
      myeloid leukemia of monocytic lineage, AML-M5b. In this paper are reviewed (a)
      the unusual and rare phenomenon of jumping translocations in hematological
      malignancies and (b) leukemia in CD.

PMID- 10087951
TI  - Cytogenetic study of a spindle-cell rhabdomyosarcoma of the parotid gland.
AB  - The cytogenetic analysis of a spindle-cell rhabdomyosarcoma of the parotid gland
      in a 6-year-old boy is reported. The tumor cells showed an abnormal karyotype
      with a hypotriploid modal chromosome number and clonal structural rearrangements
      affecting chromosomes 1, 8, 12, 21, and 22. The tumor karyotype was: 59, XY, -1, 
      3, -4, -5, -6, +8, +8, +del(8)(q22q24), -9, -10, del(12)(q13), -15, -16, -17, 
      18, der(21)t(12;21)(p11;p11), -22, der(22)t(1;22)(q12;p11).

PMID- 10087952
TI  - Detection of monosomy 7 in bone marrow by fluorescence in situ hybridization. A
      study of Fanconi anemia patients and review of the literature.
AB  - Monosomy 7 is frequently found in the bone marrow of patients with Fanconi anemia
      (FA), marrow myelodysplasia, or acute myelogenous leukemia and is associated with
      poor prognosis. In our laboratory, cytogenetic analysis of bone marrow from an FA
      patient found 2 of 30 cells with monosomy 7, but the results of fluorescence in
      situ hybridization (FISH) indicated that 83 of 207 cells (40%) had monosomy 7.
      FISH was then used to analyze two earlier samples from the index case, neither of
      which had monosomy 7 as determined by standard cytogenetics. The FISH analysis
      determined that the first sample, taken 19 months earlier, had 8 of 200 cells
      (4%) with monosomy 7 and the second sample. taken 7 months later, contained 43 of
      200 cells (21.5%) with monosomy 7. These results indicate a slow evolution toward
      monosomy 7 in the patient's bone marrow. Standard metaphase chromosome analysis
      represents only spontaneously dividing cells, leading us to hypothesize that FISH
      was detecting monosomy 7 in nondividing cells and that it might be useful in the
      early detection of abnormal clones. To test this hypothesis, FISH was performed
      on 13 bone marrow samples from nine patients with FA who did not exhibit monosomy
      7 by cytogenetic analysis. Monosomy 7 was detected in 3.44% of nuclei in FA
      patients and in 3% of nuclei in normal controls. To date, none of these nine FA
      patients have developed monosomy 7 or leukemia. They are being monitored by
      standard cytogenetics and by FISH to determine whether monosomy 7 develops and
      whether it can be detected by FISH prior to its detection by standard
      cytogenetics. As standard practice, we have adopted FISH analysis for monosomy 7
      in all patients with FA.

PMID- 10087953
TI  - Embryonal rhabdomyosarcoma with only numerical chromosome changes. Case report
      and review of the literature.
AB  - An embryonal rhabdomyosarcoma, presenting as a retroperitoneal mass in a 15-year
      old girl, is reported. The histological and immunohistochemical picture was
      typical, except for the presence of focal chondroid differentiation.
      Interestingly, expression of the "muscle markers" desmin and alpha-sarcomeric
      actin was present in the latter areas. Cytogenetic analysis showed a hyperdiploid
      karyotype without structural chromosome changes. The pertinent literature on the
      subject is reviewed. Hyperdiploidy of the clonal type seems to occur frequently,
      but no characteristic karyotype is so far emerging.

PMID- 10087954
TI  - Effect of conditioned medium, nutritive elements and mitotic synchronization on
      the accuracy of the cytogenetic analysis in patients with chronic myeloid
      leukemia at diagnosis and during alpha-interferon therapy.
AB  - To improve the yield of the cytogenetic analysis in patients with CML at
      presentation and during alpha-interferon therapy, three culture conditions for
      bone marrow or peripheral blood cells were tested in parallel. The effects of
      5637 conditioned medium (CM), nutritive elements (NE), and methotrexate (MTX)
      cell synchronization were investigated in 10 Ph-positive (Ph+) CML patients at
      diagnosis (group 1), and in 13 Ph+ CML patients receiving treatment with alpha
      interferon (group 2). In the presence of 5637 CM and NE with or without MTX, the
      mitotic index values were significantly improved in both groups. In group 2, the
      morphological index was significantly increased when using 5637 NE, and
      percentages of abnormal cells did not differ in 5637 NE and 5637 NE MTX compared
      to the control condition. Although cessation of interferon administration before
      sampling may improve the yield of the technique, it does not seem necessary when
      using 5637 CM and NE. The variability of the response of leukemic cells to
      different culture conditions further supports the recommendation that, in
      addition to the control condition, supplementations with 5637 CM and NE with or
      without cell synchronization be used in parallel in all CML patients. Results
      suggest that, when the number of cells available is not sufficient for several
      cultures, 5637 NE with or without MTX should replace the control condition.

PMID- 10087955
TI  - Tumor necrosis factor microsatellite polymorphisms in Italian glioblastoma
      patients.
AB  - Tumor necrosis factor (TNF) genes map on the short arm of chromosome 6 and have
      been described to contain several polymorphic regions, the most informative of
      which are TNFa (13 alleles) and TNFb (8 alleles) microsatellites. We analyze TNFa
      and TNFb microsatellite polymorphisms in 58 Italian patients with glioblastoma
      (GBL) and 95 unrelated healthy controls. At the TNFb locus, we detected a
      statistically significant decrease in the TNFb4 allele in GBL patients compared
      with the controls (P = 0.002; Pcorr = 0.015). Among the patients, 8 were
      homozygous TNFb4 (+/+), 23 were TNFb4 heterozygous (+/-), and 27 were negative
      for TNFb4 (-/-). In a comparison with the controls, we detected a statistically
      significant difference (P = 0.017). In fact, although no difference was detected
      in +/-, statistically significant differences were detected both for an increase
      in -/- and for a decrease in +/+ in the patient groups (P = 0.006 and P = 0.047,
      respectively). These data suggest that TNFb4-negative individuals might
      preferentially develop a Th2-type immune response that could lead to a reduction
      in antitumor activity.

PMID- 10087956
TI  - Isochromosome (12p) and peritriploidy in a highly malignant extrarenal rhabdoid
      tumor.

PMID- 10087957
TI  - Pancreatoblastoma: a second report on cytogenetic findings.

PMID- 10087958
TI  - [Problems in oncologic pharmacology].

PMID- 10087959
TI  - [Epidemiologic aspects of hepatocellular cancer in an environmentally unsafe
      area].

PMID- 10087960
TI  - [Damage to the transforming growth factor TGF-beta type II receptor gene and
      microsatellite instability in carcinoma cells of the gastrointestinal tract].
AB  - In order to compare the frequency of damage to the transforming growth factor TGF
      beta receptor type II gene (RII gene) and microsatellite instability (MIN) in
      oncogenesis of sporadic and hereditary cancer of gastrointestinal tract (GIT), 4
      groups of carcinomas were analyzed. They included sporadic gastric (GC), family
      gastric (FGC), sporadic colorectal (CC) and hereditary nonpolyposis colorectal
      (HNPCC) carcinomas having appropriate clinical and pathological characteristics.
      Each group consisted of two types of carcinomas, one of them showing MIN. The RII
      gene damage occurred in 89% of GC (8 cases out of 9), 86% of CC (6 out of 7), 71%
      of FGC (5 out of 7), 50% of HNPCC (3 out of 6) for carcinomas coupled with MIN,
      whereas only in 6% (1 out of 18) of GC and 5% (1 out of 22) of CC for carcinomas
      without MIN. No damage to RII gene was found in the cases of hereditary
      carcinomas which did not show MIN though the number of cases analyzed was not
      sufficient for final conclusions (3 cases of FGC and 3 HNPCC). The data revealed
      a correlation between the MIN phenotype and mutations in RII gene both for
      sporadic (p < 0.001) and for hereditary (p < 0.02) cases. For all 4 groups the
      frequency of RII gene damage was found for early and advanced carcinomas. This
      suggests that the deficiency of TGF-beta receptor complex in both sporadic and
      hereditary carcinomas of GIT is revealed at early stages of tumor development and
      consequently may be responsible for tumor progression. The correlation between
      RII gene damages and MIN in GIT carcinoma cells suggests that genetic change
      predetermined the neoplasia of colorectal and gastric epithelium and partially
      overlapped for both sporadic and hereditary cases.

PMID- 10087961
TI  - [Microcirculation in gastrointestinal cancer and some possibilities of its
      correction].
AB  - Microcirculation and blood rheology were studied in 348 patients with tumors of
      the gastrointestinal tract. Such disorders as increased blood and plasma
      viscosity, aggregates of erythrocytes and their increased stability of shape were
      recorded in conjunction with hypo- and dysproteinemia, endogenous intoxication
      syndrome and microvascular disturbances. Microcirculation significantly improved
      and endoxemia was alleviated following photomodification of the blood by use of
      helium-neon laser radiation and application of an original procedure of infusion.

PMID- 10087962
TI  - [Correlation between the count of the various intraepithelial mononuclear
      leukocytes and tumor progression in the stomach].
AB  - A study of 35 gastrobioptates sampled from benign epithelial proliferates,
      adenomas with advanced epithelial dysplasia and adenocarcinomas was conducted
      using standard original procedures of staining and DNA identification. Also, the
      method of direct immunoluminescence using fluoroesceinisothiocymate-labeled
      monoclonal antibodies against human antigens CD4, CD8, CD25 and CD45 was
      employed. It was found that, among microscopic intraepithelial mononuclear
      leukocytes, only few bear the immunohistochemical markers of activity. The
      distribution of intraepithelial mononuclear leukocytes in the stomach of a cancer
      patient is changed.

PMID- 10087963
TI  - [Aromatase activity and its gene expression in tumor tissue of smokers and non
      smokers with breast cancer].
AB  - Tissue was sampled from 121 tumors of the breast. The activity of aromatase
      (estrogen synthetase) was assessed by radiobiochemical means in 61 cases; gene
      expression was evaluated with the aid of polymerase chain reaction in 14 and the
      same--by the dot-blot procedure in 46 patients. Inveterate smokers (15 years and
      more) made up 16.5%. The smokers revealed a distinct tendency towards aromatase
      activity decreasing in tumor tissue (chiefly in menopausal patients) as well as
      lower intensity of aromatase gene expression assessed in terms of polymerase
      chain reaction. Alongside with other evidence, our finding point to long-term
      smoking-related sensitivity of intratissular estrogen synthesis being higher than
      in general circulation. It also demonstrated local aromatization inhibition in
      tumor tissue, the latter being a possible mechanism which causes tumor tissue
      hormone sensitivity to change in smokers and affects course of disease.

PMID- 10087964
TI  - [The role radiography in assessing the stage of renal cancer].
AB  - The investigation included 421 cases of renal cell carcinoma with metastases of
      different localization. Tumor advancement was assessed by application of general
      view imaging, X-ray, computed and magnetic resonance tomography, ultrasound and
      osteoscintigraphy. Alterations in the lung were registered in 271 patients
      (64.4%); metastases into bones--244 (57.9%). Tumor dissemination to
      retroperitoneal lymph nodes was detected in 166, liver--96 and the brain--6
      patients.

PMID- 10087965
TI  - [C-cells in malignant epithelial tumors of the thyroid gland].
AB  - An original procedure using points to evaluate the degree of tumor cell
      differentiation was employed in examining patients with papillary (42),
      follicular (33), medullary (19) and anaplastic (2) thyroid cancer. C-cell
      hyperplasia was detected in 26 out of the total of 94 cases (27.6%). It was the
      backdrop for each form of thyroid cancer and increased as tumor cell
      differentiation decreased. Three grades of C-cell hyperplasia were identified: I-
      11-20; II--21-49 and III--over 50 cells. According to anaplastic degree, it was
      typical and atypical; according to spreading pattern--focal, diffuse and nodular.
      Typical or diffuse hyperplasia was detected in well-differentiated cell tumor,
      while the atypical pattern prevailed in poorly- and moderately-differentiated
      ones. Most attention should be given to cases of subcapsular atypical hyperplasia
      of small C-cells showing initial well-differentiated cells of medullar thyroid
      cancer (C-cell microcarcinoma).

PMID- 10087966
TI  - [Morphologic and functional features of hemopoietic microenvironment in acute
      lymphoblastic leukemia].
AB  - Data of the histological, ultrastructural and culture cell investigations of bone
      marrow microenvironment in 20 patients with acute lymphoblastic leukemia (ALL)
      are presented. Morphological and functional peculiarities of the patients' bone
      marrow stroma different from that in healthy subjects were identified. They
      included distorted histotopographic patterns of stroma-hemopoietic cell-to-cell
      interaction, obliteration of sinusoid counts, resorption on the sites of internal
      bone support structures, a changed stromal cells ratio, formation of reticular
      cell clusters in the subendosteal and perivascular bone marrow areas, fibroid
      centers, the presence of nuclear bodies in stromal cell nuclei and an intensified
      proliferation of stromal cell precursors in organ tissue cultures. Morphological
      and functional changes in bone marrow microenvironment were detected in ALL
      patients, which could have been caused both by malignant cell clones and stromal
      defects.

PMID- 10087967
TI  - [The use of fludarabine phosphate (Fludara) to treat chronic B-cell lymphocytic
      leukemia and non-Hodgkin's lymphoma resistant to standard chemotherapy].
AB  - Following monochemotherapy with fludarabin phosphate (fludara), complete (18%),
      and partial remission (27%) with stabilization (45%) was recorded in patients
      with B-cell chronic lymphocytic leukemia, most of whom were resistant to
      alkylating cytostatic drugs and their combinations containing anthracyclines.
      Long-term remission was registered in patients with low and moderate grade non
      Hodgkin's lymphoma, resistant to standard cytostatic treatment, due to the
      therapeutic synergism of fludara and cytosinarabinoside (FAVAMP).

PMID- 10087968
TI  - [Modification of the sensitivity of Ehrlich ascitic carcinoma to apoptosis by
      transfection of thymocyte DNA].
AB  - We have demonstrated earlier that the replacement of the plasma membrane
      components of Erlich adenocarcinoma cells by the ones of thymocytes facilitates
      induced apoptosis in the tumor cells. Here we questioned whether similar effect
      can be achieved by transfection of thymocyte DNA. Lyposome transfer of normal DNA
      did not change the basal level of the programmed cell death. However,
      transfection activated apoptosis induced by Roentgen irragiation or
      glucocorticoids. Probably, this effect was due to restoration suppressor genes,
      which had been lost during the process malignant transformation. These
      experiments may be useful for the development of gene therapy approaches for
      tumor sensibilisation.

PMID- 10087969
TI  - [Endovascular laser irradiation of blood in the comprehensive treatment of
      stomach cancer].
AB  - The data on the treatment of 35 patients with gastric cancer (two groups) are
      presented. In group I, surgery and chemotherapy were given; in group II-
      intravenous helium-neon laser therapy as a component of complex treatment.
      Dynamic changes in hematological and immunological indices were investigated. The
      immunological and hemopoietic indices improved after laser therapy.

PMID- 10087970
TI  - [Intraoperative colonic sorption dialysis in colonic cancer complicated with
      colonic obstruction].
AB  - The data on treatment 84 patients with large bowel carcinoma aggravated by
      occlusion ileus are discussed. The study group included 49 patients who received
      intraoperative sorption dialysis of large bowel (ISDLB). Intraoperative lavage of
      large bowel (ILLB) was given to 35 patients who were in control. A significantly
      higher detoxication effect of ISDLB was recorded by hematological and biochemical
      index dynamics analysis. Lethality dropped to 6% in the group receiving ISDLB
      (11%). The latter patients spent 15 +/- 4 days in hospital as compared to 25 +/-
      4 days in control. The postoperative complication rates were 14 and 29%,
      respectively. ISDLB should be indicated in complex therapy of bowel carcinoma
      aggravated by occlusion ileus because of its cleansing effect which significantly
      reduces end-genuous intoxication.

PMID- 10087971
TI  - [Results of endovascular interventions (embolization and chemoembolization) in
      the treatment of operable and extensive kidney cancer].
AB  - The results of an all-round examination and complex treatment of 323 patients
      with renal cell carcinoma were evaluated. Locally advanced tumors were diagnosed
      in 143 (44.3%) and extended ones--in 180 (66.7%). In patients with locally
      advanced tumor who had undergone nephrectomy after embolization or
      chemoembolization, 12-, 24- and 36-month survival rates showed no significant
      difference. In patients with extended renal carcinoma, 2- and 3-year survival was
      significantly higher after chemoembolization than after standard embolization of
      the renal artery.

PMID- 10087972
TI  - [The use of dioxadet in chemoembolization of the hepatic artery in primary and
      metastatic cancer of the liver].
AB  - An evaluation of the treatment of 42 patients with extended primary hepatic
      tumors and multiple intrahepatic metastases of colorectal carcinoma established
      the effectiveness of a newly-developed fat-soluble cytostatic drug--dioxadet,
      used for chemoembolization particularly, when foci fed from small arterial
      vessels were located along the periphery.

PMID- 10087973
TI  - [The role of cardioxane (ICRF-187) in the prevention of cardiotoxicity of
      anthracyclines in the combined drug therapy of extensive ovarian cancer].
AB  - The investigation was concerned with clinical application of cardioxane
      (dexrazoxan, ICRF-187) which is intended to counteract the cardiotoxic effect of
      anthracycline drugs. It was tested in 24 courses of combination chemotherapy
      (CAP) in 48 cases of extended ovarian tumor. The "threshold" total dose of
      doxorubin (500 mg/m2) which caused persistent cardiomyopathy in such patients as
      well as cases of relapse was practically never reached due to the absence of
      therapeutic effect. The total dose of doxorubicin of 120 mg/m2 raised the
      likelihood of acute cardiac intoxication. With prophylactic administration of
      cardioxane, clinical signs of acute cardiointoxication were slight; irreversible
      intoxication was recorded in 0.8%. The drug improved tolerance; it neither
      increased the overall toxicity of combination chemotherapy nor affected the
      results.

PMID- 10087974
TI  - [The use of Tantum Rosa in the prevention and treatment of radiation-induced
      vaginitis and proctitis].

PMID- 10087975
TI  - [Trial of the clinical use of Tantum Rosa after uterine extirpation for
      gynecologic malignancies].
AB  - A new non-steroid antiphlogistic medicine--tantum rosae--was tested in the course
      of treatment of 12 patients with gynecological malignancies. No postoperative
      complications in the area of the vaginal stump were reported. Good tolerance,
      primary adhesion of the stump and shorter admission period were recorded.

PMID- 10087976
TI  - [Randomized trial of two administration schedule of bonephos (Clodronate) in
      patients with painful bone metastasis].
AB  - A randomized study of two intravenous schedules of Clodronate showed that a
      single 4-hour infusion of 1500 mg Clodronate proved significantly more effective
      than the traditional 2 hours infusion of 300 mg during 5 days. The regimen may
      prove preferable in therapy of patients with painful bone metastases.

PMID- 10087977
TI  - [Computer diagnosis of postmenopausal osteoporosis].

PMID- 10087978
TI  - [Cancer of the major duodenal papilla (autopsy data)].

PMID- 10087979
TI  - [A giant-cell tumor-like formation in the parietal bone].

PMID- 10087980
TI  - [A case of splenic hamartoma].

PMID- 10087981
TI  - [Fallo-urethroplasty after amputation of the penis for malignant disease].

PMID- 10087982
TI  - [Adjuvant therapy for colon cancer].

PMID- 10087983
TI  - [International statistical classification of neoplasms, 10th revision: structural
      features and continuity in code comparison].

PMID- 10087984
TI  - [Quality of life of oncologic patients].

PMID- 10087985
TI  - Hematologically important mutations: red cell pyruvate kinase (2nd update).

PMID- 10087986
TI  - Two mechanisms for toxic effects of hydroxylamines in human erythrocytes:
      involvement of free radicals and risk of potentiation.
AB  - The toxic potency of three industrially used hydroxylamines was studied in human
      blood cells in vitro. The parent compound hydroxylamine and the O-ethyl
      derivative gave very similar results. Both compounds induced a high degree of
      methemoglobin formation and glutathione depletion. Cytotoxicity was visible as
      Heinz body formation and hemolysis. High levels of lipid peroxidation occurred,
      in this respect O-ethyl hydroxylamine was more active than hydroxylamine. In
      contrast H2O2 induced lipid peroxidation was lowered after O-ethyl hydroxylamine
      or hydroxylamine treatment, this is explained by the ferrohemoglobin dependence
      of H2O2 induced radical species formation. Glutathione S-transferase (GST) and
      NADPH methemoglobin reductase (NADPH-HbR) activities were also impaired, probably
      as a result of the radical stress occurring. The riboflavin availability was
      decreased. Other enzyme activities glutathione reductase (GR), glucose 6
      phosphate dehydrogenase (G6PDH), glucose phosphate isomerase and NADH
      methemoglobin reductase, were not or only slightly impaired by hydroxylamine or O
      ethyl hydroxylamine treatment. A different scheme of reactivity was found for N,O
      dimethyl hydroxylamine. This compound gave much less methemoglobin formation and
      no hemolysis or Heinz body formation at concentrations up to and including 7 mM.
      Lipid peroxidase induction was not detectable, but could be induced by subsequent
      H2O2 treatment. GST and NADPH-HbR activities and riboflavin availability were not
      decreased. On the other hand GR and G6PDH activities were inhibited. These
      results combined with literature data indicate the existence of two different
      routes of hematotoxicity induced by hydroxylamines. Hydroxylamine as well as O
      alkylated derivatives primarily induce methemoglobin, a process involving radical
      formation. The radical stress occurring is probably responsible for most other
      effects. N-alkylated species like N,O-dimethyl hydroxylamine primarily lead to
      inhibition of the protective enzymes G6PDH and GR. Since these enzymes play a key
      role in the protection of erythrocytes against oxidative stress a risk of
      potentiation during mixed exposure does exist.

PMID- 10087987
TI  - Low-dose high-frequency enzyme replacement therapy prevents fractures without
      complete suppression of painful bone crises in patients with severe juvenile
      onset type I Gaucher disease.
AB  - Patients with type I Gaucher disease often present as adults with a mild disease
      and with less severe genetic mutations, especially 1226G/1226G (N370S/N370S).
      Patients presenting as children have an excess of compound heterozygotes of N370S
      and other mutations, such as 84GG, 1448C (L444P) and IVS2 + 1 in whom bone
      disease is common. We report our experience with low-dose high-frequency enzyme
      replacement therapy in such severely affected children. Ten patients (with severe
      juvenile onset type I Gaucher disease) were treated. Alglucerase (Ceredase) was
      infused at 30 units/kg/month in 13 fractions/month for more than one year. Bone
      disease was used as the main criterion for evaluating treatment results. No
      fractures occurred in spite of the fact that bone crises occurred in four
      patients after 12 to 24 months of treatment, in two during the third year, and in
      one during the fifth year. Nonosseous manifestations improved with treatment. The
      ability of low-dose high frequency alglucerase to prevent fractures in the
      presence of continuing bone crises was demonstrated.

PMID- 10087989
TI  - Splenic "regeneration" after partial splenectomy for Gaucher disease:
      histological features.
AB  - Partial splenectomy for Gaucher disease is often followed by reenlargement of the
      splenic remnant. It remains unclear if this process is due to tissue regeneration
      or to continued deposition of glucocerebroside in the reticuloendothelial system
      or both. We compared the splenic architecture before and after reenlargement in
      three cases of failed repeated partial splenectomy after two, six and five years.
      Using the number of lymphoid follicles per hundred low power fields (LF/LPF) as
      an arbitrary index, we found that prior to the first operation 18, 20 and 27
      lymphoid follicles were present per one hundred low power fields, while at the
      second operation, the corresponding rates were 11, 15 and 17; in control spleens,
      an average of 712.5 lymphoid follicles were present in one hundred low power
      fields. The difference in the LF/LPF ratio before and after reenlargement, led us
      to speculate that splenic re-enlargement in Gaucher disease is mainly the result
      of the continued deposition of the glucocerebroside in the reticuloendothelial
      system of the splenic remnant, though some degree of true regeneration as well
      cannot be completely ruled out. These findings are compared with animal studies
      and results for partial splenectomy on humans, performed for trauma. Further
      studies in patients with Gaucher disease are warranted to better define the
      underlying mechanism of splenic reenlargement.

PMID- 10087988
TI  - Commentary: low-dose high-frequency enzyme replacement therapy prevents fractures
      without complete suppression of painful bone crises in patients with severe
      juvenile onset type I Gaucher disease.

PMID- 10087990
TI  - Transferrin receptor mutation analysis in hereditary hemochromatosis patients.
AB  - The Cys282-->Tyr mutation in the HFE gene is carried by the majority of
      hereditary hemochromatosis patient chromosomes, yet some patients do not seem to
      harbor any mutation in this gene. This suggests a possibility that these patients
      may have a mutation in other genes in the same pathway as HFE. We analyzed the
      cDNA sequences of transferrin receptor (TFR), which was recently shown to
      interact with HFE, in twenty-one hereditary hemochromatosis patients including
      sixteen individuals who did not carry a Cys282-->Tyr mutation. A nucleotide
      substitution (424A-->G), which resulted in the Ser142-->Gly amino acid
      substitution, was the only amino acid polymorphism detected in the open reading
      frame of the TFR gene in these patients. This amino acid substitution was a
      rather common polymorphism in the general population (49%) and its frequency did
      not significantly differ in the hereditary hemochromatosis (HH) patients
      regardless of the HFE genotype. Thus, amino acid changes in the TFR gene do not
      appear to play a role in HH even when the patients do not have a HFE mutation.
      However, this study does not rule out the possibility of the involvement of
      mutations in non-coding regions.

PMID- 10087991
TI  - Development of a condensed locus control region cassette and testing in
      retrovirus vectors for A gamma-globin.
AB  - Retrovirus vectors for A gamma-globin are being developed for the treatment of
      beta chain hemoglobinopathies. Toward the goal of achieving therapeutic
      expression levels, core elements of the beta-globin locus control region (LCR)
      hypersensitive sites (HS) were screened for enhancer activity in erythroid MEL
      and K562 cell lines using a drug-resistant colony assay. When used alone, core
      elements of HS1, HS3, and HS4 showed no activity and a fragment for HS2 showed
      only modest activity in the colony assay. However, a 1.1 kb combination of
      fragments for HS2, HS3, and HS4 (termed a nLCR) enhanced colony formation 17-fold
      in K562 cells and 94-fold in MEL cells. Addition of an HS1 fragment enhanced nLCR
      activity only modestly in MEL cells. When linked to a beta-globin gene, the 1.1
      kb nLCR enhanced globin mRNA expression to 82% per copy of mouse alpha-globin in
      transfected MEL cells. Inclusion of a nLCR in retrovirus vectors containing a
      beta-globin promoter and various A gamma-globin gene expression cassettes
      resulted in extreme genetic instability and reduced titers. Specific deletions
      were abrogated by removing homologous sequences, but random recombinations were
      still observed at significant frequencies. In MEL cells containing intact
      provirus, A gamma-globin mRNA produced by an optimal vector containing the nLCR
      was only 2-fold higher (8.5% vs. 3.9% per copy of mouse alpha-globin) compared to
      the same vector without the nLCR. These data suggest that vector elements detract
      from the ability of the nLCR to enhance expression of the beta pr.A gamma
      cassettes.

PMID- 10087992
TI  - Genetic and physical mapping of the Lps locus: identification of the toll-4
      receptor as a candidate gene in the critical region.
AB  - On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses,
      the location of the mouse Lpsd mutation was circumscribed to a genetic interval
      0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the
      mutation were examined in mapping. Most of these were previously unpublished
      polymorphic microsatellites, identified by fragmentation of YAC and BAC clones
      spanning the region of interest. Lpsd was found to be inseparable from the
      microsatellite marker D4MIT178, and from three novel polymorphic microsatellites
      identified near D4MIT178. The mutation was confined between two novel
      microsatellite markers, herein designated "B" and "83.3." B lies centromeric to
      the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3
      lies distal to the mutation and was separated by three crossovers in a panel of
      493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the
      critical region. Estimates based on pulsed field gel electrophoresis and
      fluorescence in situ hybridization indicate that the The B-->83.3 interval is
      about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd
      was also assigned, and found to occupy approximately 1.2 Mb of physical size. To
      identify gene candidates, nearly 40,000 sequencing runs were performed across the
      critical region. Selective hybridization and exon trapping were also employed to
      identify genes throughout the "zero" region. Only a single intact gene was
      identified within the entire critical region. This gene encodes the Toll-4
      receptor, a member of the IL-1 receptor family.

PMID- 10087993
TI  - Identification of upstream regulatory elements that repress expression of adult
      beta-like globin genes in a primitive erythroid environment.
AB  - Our investigations have focused on localizing cis-elements responsible for the
      down regulation of the adult beta-like globin genes (delta and beta) in immature,
      or primitive erythroid tissues. We studied their activity after transfection into
      K562 cells, an erythroleukemia cell line with an embryonic-fetal phenotype.
      Analyzed DNA sequences included delta and beta 5' flanking regions extending from
      approximately -500 to +50bp (promoter regions), truncated delta and beta 5'
      flanking regions extending from approximately -250 to +50 bp, and chimeric
      promoter constructions, which consisted of a distal delta or beta fragment fused
      to a proximal beta or delta sequence. In CAT reporter constructions no
      appreciable level of CAT activity was supported by the beta globin promoter, and
      only low level activity by the delta promoter. Truncation of the beta globin
      promoter led to a 2-3 fold increase in promoter activity. In contrast, deletion
      of the upstream portion of the delta promoter led to a 10 fold decrease in
      expression. Coupling of the upstream beta globin sequence from approximately -500
      to -250 bp to the truncated delta promoter fragment led to complete extinction of
      transcription activity, consistent with a negative regulatory effect of the beta
      globin gene upstream element(s). Fusion of the upstream portion of the delta
      promoter to the truncated beta globin promoter yielded a modest increase in
      promoter strength relative to the truncated beta gene promoter, indicating the
      presence of a positive transcriptional element(s) in the upstream delta globin
      regulatory region. Site-directed mutagenesis of binding sites for the repressor
      proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking
      region led to a 4-6 fold increase in promoter activity. DNase I footprinting of
      the upstream delta-globin region revealed protected sequences corresponding to
      consensus binding sites for GATA-1 and BP2. These results confirm that sequences
      in the upstream promoter region of the adult beta globin gene contribute to its
      factor-mediated suppression early in development and then may modulate its
      expression at a later stage.

PMID- 10087994
TI  - The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal
      hemoglobinuria includes large deletions and small duplications.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder
      characterized by chronic hemolysis with hemoglobinuria and venous thrombosis. PNH
      clones arise through somatic mutations in the X-linked PIG-A gene that occur in
      early hematopoietic stem cells. Here we report 28 previously undescribed
      mutations; we confirm that somatic mutations are spread throughout the entire
      coding region of the PIG-A gene and that the majority are frameshift mutations
      producing a non-functional PIG-A protein (PIG-A(o)). In addition, we found 1
      total deletion of the PIG-A gene, and 2 short nucleotide duplications. Although
      mutations are spread throughout the entire coding region, we observe more
      missense mutations in exon 2 than in the other exons. The increasing number of
      identified missense PIG-A mutations should help elucidate structure-function
      relationships in the PIG-A protein.

PMID- 10087995
TI  - Blood cell damage after in vitro irradiation of fresh whole blood with 630 nm
      laser light.
AB  - A study on blood cell damage after irradiation of fresh whole blood with 630 nm
      laser light was carried out in vitro. Various fluence rates of laser light were
      used with and without cooling of blood. Damage to the blood was assessed by blood
      cell counts, osmotic fragility measurements and examination of blood films.
      Exposure of a 1 mm blood layer to 630 nm laser light without cooling led to
      changes in blood counts first detected at fluence rates of 130 mW/cm2. Changes in
      osmotic fragility first became evident at 210 mW/cm2. Increasing cell damage with
      increasing fluence rates was evident in blood films. Using the cooling device
      changes in whole blood after irradiation first occurred at a fluence rate of 293
      mW/cm2. Measurement of the fluence rates at which cell damage begins is important
      in laser induced fluorescence diagnostics and photodynamic therapy applications
      in blood or blood products using photosensitizers.

PMID- 10087997
TI  - Controversy over relevancy of LGVMA continues.

PMID- 10087998
TI  - Controversy over relevancy of LGVMA continues.

PMID- 10087999
TI  - Controversy over relevancy of LGVMA continues.

PMID- 10088000
TI  - Controversy over relevancy of LGVMA continues.

PMID- 10088001
TI  - Controversy over relevancy of LGVMA continues.

PMID- 10088002
TI  - Acupuncture resuscitation techniques questioned.

PMID- 10088003
TI  - Acupuncture resuscitation techniques questioned.

PMID- 10088004
TI  - Acupuncture resuscitation techniques questioned.

PMID- 10088005
TI  - Risks and benefits of modified-live versus killed virus vaccines in multiple-cat
      situations.

PMID- 10088006
TI  - Questions timing of publicity on new drug.

PMID- 10088007
TI  - What is your diagnosis? Primary splenic tumor and suppurative peritonitis due to
      gallbladder rupture.

PMID- 10088008
TI  - Anesthesia case of the month. Laryngeal stridor in a horse caused by an
      epiglottic cyst.

PMID- 10088009
TI  - Cachexia and nutritional issues in animals with cancer.

PMID- 10088010
TI  - Practice standards--by law, by regulation, by codes of ethics, by association's
      guidelines, or not at all?

PMID- 10088011
TI  - Compendium of chlamydiosis (psittacosis) control, 1999. Psittacosis Compendium
      Committee, National Association of State Public Health Veterinarians.

PMID- 10088012
TI  - Development of a scale to evaluate postoperative pain in dogs.
AB  - OBJECTIVE: To design and evaluate a scale for measurement of postoperative pain
      in dogs. DESIGN: Randomized, blinded, prospective study, with positive- and
      negative-control groups. ANIMALS: 36 dogs undergoing general anesthesia for
      ovariohysterectomy and 12 dogs undergoing general anesthesia without surgery.
      PROCEDURE: A pain assessment scale was developed for dogs, which incorporated
      physiologic data (heart and respiratory rates) and behavioral responses (response
      to palpation, activity, mental status, posture, and vocalization). This pain
      scale was then applied to a study in which dogs were allocated to 2 groups,
      depending on the type of medication administered (acepromazine maleate only or
      acepromazine and butorphanol) before induction of general anesthesia. The 36 dogs
      that had ovariohysterectomy were allocated to 3 groups, members of which received
      butorphanol, carprofen, or no analgesic after surgery. Dogs were scored for signs
      of pain and videotaped at 0, 1, 2, 4, 6, 8, 12, and 18 hours after surgery by an
      assessor who was blinded to the groups. Results were analyzed for significant
      differences in pain scores for single categories and total pain scores among
      groups. Video segments were scrambled and then scored by a second external
      assessor to test the repeatability of the results, using the pain assessment
      scale. RESULTS: Mean total pain scores were significantly different between the
      group of dogs that underwent general anesthesia only and each group of dogs that
      underwent general anesthesia and surgery. Pain scores for the analgesic-treatment
      groups reflected the known onset and duration of action of the analgesic used.
      Agreement between the internal and external assessors was excellent and indicated
      high precision between the 2 assessors for the population of dogs as a whole.
      CLINICAL IMPLICATIONS: Behavioral and physiologic measurements can be used
      reliably to evaluate degree of pain in dogs during the postoperative period and
      their response to analgesics.

PMID- 10088013
TI  - Brow suspension for treatment of ptosis and entropion in dogs with redundant
      facial skin folds.
AB  - Brow suspension surgery was performed on 7 dogs with redundant facial skin folds,
      associated ptosis, and entropion. The surgical technique involved subcutaneous
      placement of polyester mesh strips to suspend the upper eyelid from the dorsal
      frontalis muscle and the underlying periosteum of the skull. Visual impairment
      associated with ptosis was resolved in all dogs at the 2 week reevaluation
      period. Upper eyelid position was maintained in 4 of 7 dogs available for long
      term follow-up. One dog developed persistent draining tracts in the region of the
      implant, and removal of part of the implanted mesh was eventually required. Upper
      eyelid height in this dog, however, was maintained following mesh removal,
      probably because of fibrosis around the implant. Brow suspension is an option for
      surgical management of upper eyelid ptosis and entropion in dogs with redundant
      skin folds and avoids the need for facial skin fold excision.

PMID- 10088014
TI  - Use of ocular compression to induce vagal stimulation and aid in controlling
      seizures in seven dogs.
AB  - Ocular compression (OC) was used to treat 7 dogs with seizures. Treatment was
      accomplished by use of digital pressure applied to one or both eyes by
      veterinarians, hospital staff, or owners. The OC was believed to exert an effect
      through stimulation of the vagus nerve. Use of OC appeared to be efficacious for
      aborting seizures in 3 dogs, decreasing heart rate and causing muscle relaxation
      in 1 dog, and preventing onset of seizures in 2 other dogs. In 1 dog, rhythmic
      application of OC caused onset of rhythmic facial twitches. Administration of OC
      may be beneficial in treating seizuring dogs.

PMID- 10088015
TI  - Progesterone secreting adrenal mass in a cat with clinical signs of
      hyperadrenocorticism.
AB  - A 7-year-old 7-kg (16-lb) neutered male Himalayan cat had nonpruritic progressive
      alopecia of 9 months' duration. The cat had hyperglycemia and glucosuria.
      Physical examination revealed complete alopecia along the abdomen, inguinal area,
      medial and caudal areas of the thighs, ventral area of the thorax, and axilla.
      Clinical signs were consistent with endocrine-induced alopecia and
      hyperadrenocorticism, however, results of diagnostic tests (ACTH stimulation and
      low-dose dexamethasone suppression) were not supportive of hyperadrenocorticism.
      Abdominal ultrasonography revealed a mass cranial to the left kidney. Blood
      samples were obtained before and after ACTH stimulation to measure sex hormone
      concentrations. Analysis revealed markedly high blood progesterone concentrations
      before and after ACTH stimulation. An adrenalectomy was performed and histologic
      examination of the mass revealed a well-differentiated adrenocortical carcinoma.
      The right adrenal gland could not be viewed during surgery and was assumed to be
      atrophic. Following surgery, the hyperglycemia and glucosuria resolved. Within 4
      months of surgery, the hyperprogesteronemia had resolved, and at 12 months the
      cat's coat quality appeared normal. Findings suggest that cats with signs of
      hyperadrenocorticism should be evaluated not only for abnormal cortisol
      concentrations, but also for sex hormone abnormalities.

PMID- 10088016
TI  - Unusual metastatic behavior and clinicopathologic findings in eight cats with
      cutaneous or visceral hemangiosarcoma.
AB  - Eight cats with visceral or cutaneous hemangiosarcoma were evaluated, and unusual
      metastatic and clinicopathologic behavior was evident in each. Cutaneous
      hemangiosarcoma is generally believed to be locally aggressive and slow to
      metastasize. These 8 cats with cutaneous hemangiosarcoma, however, developed
      metastatic disease after initial surgical resection; only 1 had local regrowth of
      the tumor. All cats with visceral hemangiosarcoma had metastasis at the time of
      diagnosis, which is consistent with cats of other reports. Three of 8 cats had
      evidence of disseminated intravascular coagulation, including increased
      prothrombin time and partial thromboplastin time, decreased number of platelets,
      and anemia. These potential complications need to be considered when planning
      diagnostic and treatment protocols.

PMID- 10088017
TI  - Cytologic examination of specimens obtained by means of tracheal washes performed
      before and after high-speed treadmill exercise in horses with a history of poor
      performance.
AB  - OBJECTIVE: To evaluate results of cytologic examination of specimens obtained by
      means of tracheal washes (TW) in 42 horses with a history of poor performance.
      DESIGN: Cross-sectional case series. ANIMALS: 42 horses with a history of poor
      performance. PROCEDURE: A TW was performed via endoscopy before and after horses
      exercised on a high-speed treadmill, and specimens were evaluated microscopically
      and graded. RESULTS: Ten (24%) horses were considered to be clinically normal
      before and after exercise. Pulmonary hemorrhage was diagnosed in 8 (19%) horses.
      One horse had evidence of exercise-induced pulmonary hemorrhage (EIPH) before
      exercise and pulmonary hemorrhage and allergic or inflammatory airway disease
      (IAD) after exercise. Five (12%) horses had IAD, and 1 had IAD and pulmonary
      hemorrhage after exercise. Seven (17%) horses had evidence of EIPH and IAD in
      both specimens. Four (10%) horses with EIPH had an increase in the proportion of
      hemosiderophages in the specimen obtained after exercise. Specimens obtained
      before exercise in 6 (14%) horses were not representative of the respiratory
      tract and could not be compared with specimens obtained after exercise. CLINICAL
      IMPLICATIONS: Interpretation of TW specimens obtained before and after exercise
      differed for only 5 of 36 (14%) horses. Specimens obtained after exercise were
      more likely to reveal airway disease. All specimens obtained after exercise
      adequately represented the respiratory tract, whereas 6 specimens obtained before
      exercise did not. Specimens obtained after exercise contained more airway
      secretions and had less cytologic evidence of pharyngeal contamination.
      Therefore, we recommend that TW samples be obtained after exercise in horses.

PMID- 10088018
TI  - Presumed moxidectin toxicosis in three foals.
AB  - Outcome and complications associated with administration of moxidectin gel to 3
      foals < 4 months old are described. Two foals became comatose but survived
      following supportive treatment. One foal died following loss of consciousness
      associated with moxidectin administration. Risk of moxidectin overdose exists,
      because horse owners often fail to read or comprehend the package insert
      instructions pertaining to use of the syringe-locking mechanism. In addition,
      moxidectin should not be administered to foals < 4 months old, because it is
      likely that treated foals will become comatose.

PMID- 10088019
TI  - Dental wear and growth performance in steers fed sweetpotato cannery waste.
AB  - OBJECTIVE: To determine whether feeding sweetpotato cannery waste (SPCW) to
      cattle had adverse effects on dental wear, growth performance, or ruminal
      tissues. DESIGN: Clinical trial. ANIMALS: 36 Holstein steers. PROCEDURE: Steers
      were assigned to 1 of 3 groups. All steers received ryegrass hay ad libitum. In
      addition, steers in group 1 were fed 3.2 kg of corn and soybean meal/steer/d,
      steers in group 2 were fed 0.45 kg of soybean meal/steer/d and SPCW ad libitum,
      and steers in group 3 were fed a mixture of SPCW and broiler litter ad libitum.
      Samples of rumen fluid were collected on day 56. Steers were slaughtered on day
      84, and samples of rumen were submitted for histologic examination. Teeth from
      control steers were removed, and calcium ion loss in response to etching with
      2.28% lactic acid solutions buffered to pH of 3.75, 4.0, 4.25, 4.5, and 4.75 was
      determined. RESULTS: Average daily gain was lower for steers fed SPCW than for
      steers in the other 2 groups. Steers fed the SPCW-broiler litter mixture had only
      mild increases in tooth wear and tooth color scores, compared with control
      steers, whereas steers fed unbuffered SPCW had substantial increases in tooth
      wear and tooth color scores. Histologic abnormalities were detected in rumens
      from steers fed diets containing SPCW. Calcium ion loss decreased as pH of the
      etching solution increased. CLINICAL IMPLICATIONS: Results indicate that feeding
      cattle unbuffered SPCW can cause dental erosion, ruminal epithelial changes, and
      poor growth; however, SPCW buffered with broiler litter can be used as a cattle
      feed.

PMID- 10088020
TI  - Comparison of topical application of oxytetracycline and four nonantibiotic
      solutions for treatment of papillomatous digital dermatitis in dairy cows.
AB  - OBJECTIVE: To compare efficacy of topical treatment with oxytetracycline solution
      or 1 of 4 nonantibiotic solutions among dairy cows with papillomatous digital
      dermatitis (PDD). DESIGN: Randomized field trial. ANIMALS: 66 cows in a single
      herd. PROCEDURE: Cows were randomly assigned to be treated with oxytetracycline
      solution; a commercial formulation of soluble copper, peroxide compound, and a
      cationic agent; 5% copper sulfate solution; acidified ionized copper solution;
      hydrogen peroxide-peroxyacetic acid solution; or tap water. Cows were examined 14
      and 30 days after initial treatment. During each examination, pain and lesion
      scores were recorded. RESULTS: On the basis of pain and lesion scores,
      oxytetracycline and the commercial formulation appeared equally effective for
      treatment of PDD and significantly more effective than 5% copper sulfate
      solution, acidified ionized copper solution, hydrogen peroxide-peroxyacetic acid
      solution, and tap water. Proportions of cows with signs of pain or visible
      lesions after treatment were significantly lower for cows treated with
      oxytetracycline or the commercial formulation than for cows in the other groups.
      CLINICAL IMPLICATIONS: Oxytetracycline and a commercial formulation of soluble
      copper, peroxide compound, and a cationic agent appeared to be effective for
      treatment of PDD in dairy cows.

PMID- 10088021
TI  - Studies of spontaneous fluctuations in congestion and nasal mucosal
      microcirculation and the effects of oxymetazoline using rhinostereometry and
      micromanipulator guided laser Doppler flowmetry.
AB  - The mucosa of the inferior turbinate was studied using rhinostereometry and
      micromanipulator-guided laser Doppler flowmetry in 10 healthy volunteers. First,
      spontaneous fluctuations were studied measuring congestion and multiple
      microcirculatory parameters simultaneously every 2 minutes. The subjects were
      then challenged with oxymetazoline using the same measuring technique studying
      the effects of the challenge during 12 minutes. There were spontaneous variations
      in congestion of up to 2.1 mm and variations in perfusion from 38% to 175% of
      average. There was no correlation between congestion in itself, or change in
      congestion, to perfusion or any other microcirculatory parameter. After challenge
      with oxymetazoline there was a rapid decrease in perfusion at 3 minutes after
      which there were no significant changes. The congestion decreased gradually
      throughout the procedure. Because congestion reflects the filling of the venous
      sinusoids and the flowmetry the state of the superficial vessels, we conclude
      that there are spontaneous short-term fluctuations in the sympathetic tone with
      independent actions on the different vessels. After challenge with a
      sympathomimetic drug, there was a decrease in both swelling and flow, but not
      synchronized. The combination of rhinostereometry and micromanipulator-guided
      laser Doppler flowmetry is a useful tool to study the dynamics of intranasal
      challenge reactions.

PMID- 10088022
TI  - Video-endoscope versus endoscope for paranasal sinus surgery: influence on visual
      acuity and color discrimination.
AB  - Endoscopic and video-endoscopic visual acuity and color discrimination were
      investigated using a standard disk for testing visual acuity and a color
      discrimination test. A 1-chip-CCD-Camera (CCC) or 3-chip-CCD-Camera plus digital
      image processing (digivideo) on the endoscope and a 15 inch high resolution video
      monitor were used. Color discrimination was investigated by comparing the ability
      to sort colored disks of low chromatic saturation (desaturated Panel D-15 Test),
      ranging from yellow to red, under direct vision or via monitor using the same 1
      CCC- and 3-CCC-system. Visual acuity deteriorated by 1.58 +/- 0.16 steps (+/-
      SEM) for the 1-CCC and 1.21 +/- 0.16 steps for the 3-CCC plus digivideo compared
      to vision through the endoscope (p < 0.001 and p < 0.001). Visual acuity was
      significantly better for the 3-CCC-video-endoscope compared to the 1-CCC-video
      endoscope (p = 0.0045). The difference in color discrimination between the naked
      eye and the 1-CCC-monitor system was not significant. More mistakes were made
      with the 3-CCC-monitor system. The impairment of image quality with the video
      endoscope, which is experienced by many surgeons, is reflected in a marked loss
      of visual acuity in our experiments. Sharpness and contrast of the video-image
      are significantly enhanced by the 3-CCC plus digital image processing, compared
      to the 1-CCC. Color discrimination, however, was not impaired by the 1-CCC,
      indicating that color perception with the video-endoscope can be very good and
      may not contribute significantly to the loss of image quality.

PMID- 10088023
TI  - Endoscopic resection of fibro-osseous lesions of the paranasal sinuses.
AB  - Fibro-osseous tumors, including osteomas, ossifying fibromas, and fibrous
      dysplasia, are not uncommon benign lesions arising in the paranasal sinuses.
      Conventional wisdom advocates resection when these lesions are symptomatic, or
      when they exhibit rapid growth. Traditionally, resection has been performed via a
      variety of open approaches. With the advent of sinonasal endoscopy in the mid
      1980s, and subsequent advances in technology and surgical techniques, endoscopic
      management of some of these lesions is now feasible. To date, a search of the
      literature reveals only three case reports of osteomas resected with endoscopic
      guidance. We present a series of 10 symptomatic fibro-osseous lesions (nine
      osteomas and one fibrous dysplasia) occurring in nine patients in which
      endoscopic techniques were used. Seven ethmoid and frontal recess osteomas were
      resected transnasally and one sphenoid sinus fibrous dysplasia was resected using
      a transseptal transsphenoidal approach with the assistance of direct endoscopic
      visualization. There were two anticipated CSF leaks that were recognized and
      repaired at the time of surgery. There were no other complications and no tumor
      recurrence. All patients noted improvement in preoperative symptoms. We discuss
      patient selection, operative techniques and strategies, and the advantages and
      disadvantages of the endoscopic approach in the management of paranasal sinus
      fibro-osseous lesions.

PMID- 10088024
TI  - Endoscopic transsphenoidal biopsy of the sphenoid and clival mass.
AB  - Abnormalities of the clivus/skull base occur most commonly as a result of disease
      spread from adjacent structures, but can also occur from primary involvement of
      the clivus. Traditionally, definitive diagnosis was made by CT guided biopsy or
      craniotomy. However, lesions can occur in this area that are not amenable to CT
      guided biopsy or craniotomy. Endoscopic transsphenoidal surgery can provide a
      safe method for obtaining a clival biopsy, debulking of tumor tissue, or
      definitive treatment without the morbidity and mortality of a craniotomy. This
      study was designed to describe our experience with the endoscopic approach to the
      skull base and clivus via the sphenoid sinus. A series of seven patients
      underwent endoscopic transsphenoidal biopsy of a sphenoid clival lesion. All
      patients avoided anticipated craniotomy, and definitive pathology was obtained in
      five of six patients. In two cases, excisional biopsy proved to be therapeutic.
      There were no deaths, and major complications included one CSF leak and one
      intraoperative hemorrhage, both of which were controlled immediately. The
      experience gained with these patients demonstrates the feasibility and safety of
      this new application of endoscopic sinus surgery for the diagnosis and possible
      treatment of lesions of the sphenoid and clivus.

PMID- 10088025
TI  - Development of the paranasal sinuses in children with sinus disease.
AB  - In a previous report, the authors defined the normal development of the paranasal
      sinuses. Landmarks and dimensions relevant to functional endoscopic sinus surgery
      were measured on the computed-tomography images of 145 children who were free of
      significant sinusitis. The present study compares those normal values to the same
      measurements in 235 cases of sinus disease. No significant difference was found
      between normal and diseased groups in any of the 10 dimensions originally
      reported or in six derived measures. There appears to be no association between
      sinus disease and any of these dimensions. The previously reported norms are
      applicable to cases of pediatric sinus disease.

PMID- 10088026
TI  - Effects of IL-1 beta, TNF-alpha, and TGF-beta on ciliary beat frequency of human
      nasal ciliated epithelial cells in vitro.
AB  - Previous reports suggested that several cytokines may influence the ciliary beat
      of the airway ciliated epithelial cells. The aim of this study is to determine
      the effects of cytokines including IL-1 beta, TNF-alpha, and TGF-beta on ciliary
      beat frequency (CBF) of human nasal ciliated epithelial cells. CBF of cultured
      human nasal ciliated epithelial cells was measured 24 hours after incubating with
      concentrations of 0.01 ng/mL, 0.1 ng/mL, 1 ng/mL, 10 ng/mL, and 100 ng/mL of each
      recombinant human (rh) cytokine including rhIL-1 beta, rhTNF-alpha, and rhTGF
      beta. CBF was measured with time at concentrations of 1 ng/mL of rhIL-1 beta, 10
      ng/mL of TNF-alpha, and 1 ng/mL of TGF-beta solutions. CBF of the human nasal
      ciliated epithelial cells increased after addition of rhIL-1 beta and rhTNF
      alpha. Maximum CBF was observed at 1 ng/mL of rhIL-1 beta and at 10 ng/mL of
      rhTNF-alpha. CBF increased progressively to 4 hours after addition of rhIL-1 beta
      and rhTNF-alpha. Increased CBF sustained for 24 hours and decreased by 2 days.
      However, no variation of CBF was observed after addition of rhTGF-beta,
      regardless of concentrations and time. The results of this study suggest that
      during acute inflammation, IL-1 beta and TNF-alpha may have a potential role in
      defense mechanism of human nasal epithelium by regulating CBF of the nasal
      ciliated epithelial cells.

PMID- 10088027
TI  - Diagnostic significance of impression cytology in allergic rhinoconjunctivitis.
AB  - Impression Cytology (IC) is a noninvasive and easily repeated technique for
      investigating many pathologies of the conjunctiva such as dry eye, drug
      toxicities, and melanoma. In addition to skin tests and determination of serum
      IgE levels, the presence of eosinophilia in the nasal mucosa and the conjunctiva
      is an important diagnostic factor in allergic rhinoconjunctivitis. Eosinophilia
      can classically be shown by the nasal smear technique as well as IC. The nasal
      smear is a difficult test to carry out and does not always give adequate results.
      With this in mind, we collected cells from the nasal mucosa and superior
      palpebral conjunctiva from 27 patients with allergic rhinoconjunctivitis (17
      female, 10 male) using 5 x 5 mm, 0.22 micron pore-sized cellulose acetate paper.
      The specimens were fixed in 95% alcohol and were then stained with hematoxylin
      eosin and periodic acid-Schiff stain for examination by light microscopy. Taking
      the free and intraepithelial eosinophilia into consideration, the specimens were
      grouped. Of all patients, 92.6% and 85.2% had nasal and conjunctival
      eosinophilia, whereas 44.4% and 25.9% had nasal and conjunctival mononuclear
      cells, respectively. Our study has shown that IC is a very reliable and practical
      technique that offers a valuable alternative test for investigating both the
      intraepithelial and free eosinophilia in allergic rhinoconjunctivitis and other
      pathologies that cause cytologic changes.

PMID- 10088028
TI  - Monoclonal antibody-detectable carbohydrate epitopes of human nasal secretions
      are differentially expressed in tissue and diseases.
AB  - To study the differential carbohydrate expression of airway secretions, we have
      produced a series of monoclonal antibodies that recognize human nasal secretory
      cell products. Mice were immunized with purified nasal secretion from patients
      with chronic sinusitis (CS) and hybridomas were selected by ELISA and
      immunohistochemical staining of the maxillary sinus mucosa from patients with CS.
      Eighteen antibodies were obtained. Antibody HCS 18 reacted with epithelial goblet
      cells, antibody HCS 4, 5, 6, and 16 stained submucosal gland cells, and antibody
      HCS 13 and 15 reacted with epithelial goblet cells, submucosal gland cells, and
      endothelial cells of vessels. The other eleven antibodies recognized epithelial
      goblet cells and submucosal gland cells. Cross-reactivity of these antibodies
      with secretory cells in other organs and in other species was determined and the
      different staining pattern was observed between upper and lower airway tissue,
      suggesting that secretory products from upper and lower airways may be different.
      Reactivity of the antibodies with nasal secretory cells was also examined in
      patients with perennial allergic rhinitis (AR) and normal subjects. Antibody HCS
      18 weakly reacted with nasal glands in the tissue from CS and AR patients, but
      minimally reacted with gland cells in normal tissue. Antibody HCS 1 and 7
      partially lost their reactivity with nasal epithelium of inferior turbinate from
      normal subjects and AR patients. These antibodies may be useful to study nasal
      secretions.

PMID- 10088029
TI  - Nasal airway resistance and olfactory acuity following transsphenoidal pituitary
      surgery.
AB  - Rhinological problems after a transseptal transsphenoidal approach for pituitary
      tumors were prospectively investigated in 25 patients with special reference to
      nasal airway resistance and olfactory acuity. Five patients showed a significant
      increase in the unilateral and/or total nasal airway resistance. Endoscopic
      observation of the nasal cavity revealed the presence of crust formation,
      hypertrophy of the inferior turbinate, or synechiae. Three patients showed a
      significant deterioration in olfactory acuity. Coronal CT views with good
      visualization of the olfactory cleft were helpful in evaluating causes of
      hyposmia postoperatively.

PMID- 10088030
TI  - Ultrastructural localization of NADPH-diaphorase activity in the endothelial
      cells of human nasal respiratory mucosa.
AB  - The cavernous sinuses are the most peculiar feature of the nasal
      angioarchitecture, due to their ability to retain a large quantity of blood in
      reply to a variety of topical and systemic stimuli. Recently, nitric oxide (NO)
      has seemed to be crucially involved in the nasal vascular regulation. The
      distribution of NO-synthase (NOS), the enzyme that catalyzes the formation of NO,
      was studied in the endothelium of nasal blood vessels by the ultracytochemical
      detection of reduced nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPH-d) enzymic activity. The endothelium of the cavernous sinuses appeared
      strongly positive, whereas the endothelium of arterioles was occasionally
      labeled. The endothelial cells of capillaries and venules were found to be NADPH
      d negative. The strong enzymic activity observed in the cavernous sinuses
      suggests a major role of NO in the capacitance vessels compared to the resistance
      vessels. The hypothesis of a reciprocal inhibition between the NOS enzymic
      pathways present in the respiratory epithelium and in the endothelium of
      cavernous sinuses is put forward. The nasal disorders characterized by anomalous
      vasomotility and vascular permeability could be caused in part by the irregular
      control of these complex interactions.

PMID- 10088031
TI  - Efficacy and safety of levocabastine nasal spray for seasonal allergic rhinitis.
AB  - This multicenter, double-blind, placebo-controlled trial evaluated the efficacy
      and safety of levocabastine nasal spray, a potent and selective H1-receptor
      antagonist, in the control of histamine-mediated symptoms of seasonal allergic
      rhinitis. Adults with > or = 2 year history of allergic rhinitis due to Mountain
      Cedar were randomized to treatment with levocabastine nasal spray (0.2 mg twice
      daily) or placebo for 28 days during the 1994-1995 Mountain Cedar allergy season.
      Patients assessed the severity of their rhinitis symptoms on a four-point scale
      twice daily. At the end of the trial, patients also performed a global evaluation
      of treatment efficacy on a five-point scale. Overall for the 4-week treatment
      period, levocabastine nasal spray significantly reduced major nasal (runny nose
      and sneezing) and primary rhinitis (runny nose, sneezing, and itchy/gritty eyes)
      symptoms compared with placebo on both repeated measures (p = 0.023; p = 0.01)
      and ANOVA (p = 0.003; p < 0.001) analyses. Global evaluations of treatment
      efficacy at the end of the trial significantly favored levocabastine over placebo
      (p = 0.002). Overall, the incidence of adverse events was similar for both
      treatment groups. In general, most adverse events were mild in intensity, with
      sinusitis (17% each group), headache (17% placebo, 14% levocabastine), and
      rhinitis (8% placebo, 2% levocabastine) most commonly reported. Levocabastine
      nasal spray 0.2 mg twice daily was significantly more effective than placebo in
      the relief of histamine-mediated symptoms in patients with seasonal allergic
      rhinitis and was well tolerated over the 28-day treatment period.

PMID- 10088032
TI  - Clinical value of olfactory function tests after endoscopic sinus surgery: a
      short-term result.
AB  - Functional endoscopic sinus surgery (FESS) is now the surgical procedure of
      choice for treating chronic sinusitis in patients of all ages. We performed the
      olfactory function test before and after FESS and assessed its clinical value.
      From February 1996 through July 1996, 50 bilateral sinusitis patients had
      received FESS, butanol threshold test, and odor identification test, performed
      preoperatively, at postoperative 1 month, and at postoperative 2 months. We
      analyzed preoperative computed tomography to determine the grade of sinusitis and
      status of the olfactory cleft. The status of the olfactory cleft significantly
      influenced the preoperative olfactory threshold score (p < 0.001). At 2 months
      postoperatively, the subjective symptoms of the patients were improved in 96% and
      objective olfactory threshold were improved in 68% of patients. There was no
      correlation between subjective symptoms and olfactory threshold improvement. Our
      study suggests that the olfactory threshold test may help predict the result of
      FESS, but for more accurate and reliable assessment, we should consider other
      objective methods like anterior rhinomanometry, acoustic rhinometry, ciliary beat
      frequency, and postoperative endoscopic findings.

PMID- 10088033
TI  - Acoustic rhinometry evaluation of nasal response to histamine and antigen in
      guinea pigs.
AB  - The effects of antigen and histamine on the changes of nasal passage patency in
      112 guinea pigs with or without allergic rhinitis were evaluated by acoustic
      rhinometry. The percent change of volume from the nostril to 2 cm into the nasal
      cavity showed significant reduction of 31.10 +/- 4.11% at 10 minutes and 31.10 +/
      4.11% at 30 minutes after antigen challenge in sensitized guinea pigs. The
      pretreatment with ketotifen, an H1-histamine receptor antagonist as well as mast
      cell stabilizing drug, blocked dose-dependently the effects of antigen on those
      changes in volume. Furthermore, instillation of 10(4) micrograms/mL histamine
      reduced significantly nasal passage patency to 33.77 +/- 4.63% at 10 minutes and
      42.76 +/- 3.32% at 30 minutes after challenge compared with that before challenge
      and ketotifen inhibited the effects of histamine, which indicated that histamine
      is an important mediator of allergic upper airway responses in guinea pigs. These
      results show that acoustic rhinometry is a useful technique to assess the nasal
      blockade in allergic guinea pigs.

PMID- 10088034
TI  - Penrose and sib-pairs.
AB  - Penrose's sib-pair papers (1935-1953) are discussed in relation to recent
      applications. His essential contribution that parental typing was an inefficient
      addition to sib-pair data for linkage detection remains. Parents now have even
      less to offer with contemporary markers in the detection of linkage, although not
      the enumeration of haplotypes. Attention is drawn to two little known papers by
      Penrose on multifactorial disease, and it is suggested that this term should
      replace polygenic in relation to family analyses. The convention established by
      Penrose, both as author and editor, of raw data being published alongside its
      analysis, which later fell into disuse on grounds of sheer bulk, can now be
      remedied by the Internet, and has been for the largest set of sib-pair data on
      diabetes (Davies et al. Nature 371 (1994), 130-136). This is essential if the
      contributions to the identity and location of alleles possibly relevant to common
      disorders, none of which are likely to be more than suggestive in any single
      study, can be combined to assess consistency and joint evidence. Attention is
      drawn to a third little known paper by Penrose of high relevance to the strategy
      of familial investigations in multifactorial disorders. All five of the Penrose
      papers discussed here can be viewed at http:/(/)www.gene.ucl.ac.uk/anhumgen/.

PMID- 10088035
TI  - Susceptibility to spina bifida; an association study of five candidate genes.
AB  - Clues regarding candidate genes which influence susceptibility to spina bifida
      and anencephaly come from the identification of folate-associated risk factors
      and from studies of mouse mutants showing neural tube anomalies. On this basis we
      selected five candidate genes; CBS, MS, MTHFR, T (Brachyury) and BRCA1 for
      genetic analysis in 31 Dutch and 48 British NTD families. Ten polymorphisms, two
      for each gene, were used in transmission tests for disequilibrium (TDT). In six
      instances more than 50 transmissions from heterozygous parents could be examined.
      Using TDT we find evidence for an association between an allele at the T gene and
      liability to NTD in the embryo. Data from British and Dutch populations showed
      the same trend and in combination gave a chi 2TDT = 4.89, P = 0.03 (OR 2.39, CI
      95% 1.02-5.61). No association, in either population group, was found for CBS, MS
      and MTHFR, the enzymes most directly associated with the known risk factors in
      folate metabolism. The possibility of complex genetic interactions was explored;
      the data show that a Gly919 MS variant occurs more frequently in combination with
      the MTHFR thermolabile variant in mothers of NTD offspring (OR 3.94, CI 95% 1.0
      16.3).

PMID- 10088036
TI  - Mutation analysis of a putative sialyltransferase gene, the SFRS2 splicing factor
      gene and the c-myb ET-locus in two families with hereditary neuralgic amyotrophy
      (HNA).
AB  - HNA is an autosomal dominant recurrent focal neuropathy involving the brachial
      plexus. The etiology of HNA is unknown but the genetic defect most likely affects
      a non-neuronal tissue. We previously described linkage to chromosome 17q24-q25 in
      two HNA-families. Here we report the mutation analysis of two candidate genes: a
      cDNA encoding a putative sialyltransferase and the SFRS2 splicing factor
      including the c-myb ET-locus which is encoded on the opposite strand of the SFRS2
      gene. The complete protein coding regions of both genes were studied by direct
      DNA sequencing. We did not find a disease associated mutation indicating that
      these genes are most likely not involved in the pathogenesis of HNA. However, we
      identified and characterized a rare AvaII polymorphism in the SFRS2 gene and
      detected a sequencing error, leading to an amino acid change (Val11Leu) in the
      published sequence of the putative sialyltransferase.

PMID- 10088037
TI  - Construction of a bacterial artificial chromosome (BAC) contig across the
      minimally deleted region in 13q14.3 in B-cell chronic lymphocytic leukemia.
AB  - Loss of heterozygosity (LOH) analysis in B-cell chronic lymphocytic leukemia
      (BCLL) has indicated that a frequent genetic event is loss of alleles from an
      approximately 500 kb region in 13q14.3, distal to the retinoblastoma gene. We
      have used DNA markers from this region to isolate and characterize a series of
      bacterial artificial chromosomes (BACs) which span the region between markers
      D13S319 and D13S25, which represents the common region of LOH. This entire region
      appears to be contained within only two minimally overlapping BACs, representing
      a maximum distance of approximately 350 kb. This BAC contig has been used to
      position known STS, EST and gene markers within the region. We have also used a
      modified differential display/RNA fingerprinting procedure designed to isolated
      transcribed sequences from YACs to isolate two transcribed units from the region
      which have also been positioned within the contig. The construction of a BAC
      contig with minimal redundancy provides the ideal resources from which to begin
      to identify candidate genes related to BCLL.

PMID- 10088038
TI  - Major congenital malformations in United Arab Emirates (UAE): need for genetic
      counselling.
AB  - Between January 1992 and January 1995 a total of 24,233 babies born consecutively
      in Corniche Hospital which is the only maternity hospital in Abu Dhabi, the
      capital of UAE, were surveyed for the presence of major congenital malformations.
      A total of 401 infants (16.6/1000) had a major defect. Of these malformations,
      267 (67%) were associated with an estimated recurrence risk greater than 1%, and
      95 (24%) carried an estimated recurrence risk greater than 10%. This included a
      total of 91 cases of single gene disorders and 4 cases of cleft lip and palate
      where a mother and another sibling were affected putting their estimated
      recurrence risk in the high category group. When antenatal diagnosis is feasible,
      this should be considered in 60% of mothers (a total of 242). In 59% (a total of
      237) the estimated recurrence risk was > 1% and the antenatal diagnosis of the
      disorder was possible. The importance of Genetic Counselling is revealed in our
      study since more than three quarters of mothers were under 36 years old, and may
      well plan future pregnancies.

PMID- 10088039
TI  - Optimization of genome search strategies for homozygosity mapping: influence of
      marker spacing on power and threshold criteria for identification of candidate
      regions.
AB  - Mapping of genes involved in rare recessive diseases is usually difficult because
      of the lack of families with more than one affected progeny. The problem may be
      avoided by using inbred affected individuals and the strategy of homozygosity
      mapping. In practice, the use of homozygosity mapping in a genome-wide scan
      requires that a set of markers regularly spaced and spanning the whole genome are
      tested. Investigators are then faced to the problem of choosing the spacing of
      markers. To help solve this problem, we give some useful clues by computing (1)
      the expected length of the region of identity by descent around the disease
      locus, (2) the distribution, given the spacing of markers, of the number of
      affected individuals expected not to be homozygous at the marker closest to the
      disease locus and, (3) the expected type-one error. We show that even if the
      markers are very closely spaced, it is not unlikely that some affected
      individuals in the sample will not be homozygous at the marker closest to the
      disease locus. Excluding a region by the criterion that all affected individuals
      in the sample are not homozygous may then dramatically increase the rate of false
      negatives. We thus propose to relax the criterion to declare a region candidate,
      based on the sample size and the spacing of markers.

PMID- 10088040
TI  - TDT statistics for mapping quantitative trait loci.
AB  - The original transmission disequilibrium test (TDT), was introduced to test for
      linkage between a marker and a disease-susceptibility locus (Spielman et al.
      1993). Allison (1997) extended the TDT procedure to quantitative traits.
      Allison's test, however, is restrictive in that it requires family trios
      consisting of one heterozygous parent, one homozygous parent and one child, and
      considers only the situation where the marker locus is analogous to the
      quantitative trait locus itself. In this paper, we propose, investigate and apply
      a general TDT for quantitative traits that permits more than one child per
      family, does not require only one parent to be heterozygous, and allows for the
      fact that the various alleles at the marker and trait loci may be at varying
      degree of linkage disequilibrium. We also show that this TDT for quantitative
      traits is still a valid test of linkage in the presence of population
      substructure. To provide guidelines for study design, we develop analytic
      formulae for calculation of the power of the TDT for mapping quantitative trait
      loci and investigate the impact of various factors on the power. Power
      calculations show that the proposed TDT for quantitative traits is more powerful
      than Allison's basic test statistic and the extreme discordant sib pair linkage
      method. The proposed TDT statistic for quantitative traits is applied to systolic
      blood pressure variation in the Rochester Family Heart Study using an extremely
      discordant sibling pair design.

PMID- 10088041
TI  - Introduction to the complex genetics of mental disorders.

PMID- 10088042
TI  - Basic concepts in the study of diseases with complex genetics.
AB  - Most diseases run in families--this is also true of virtually all psychiatric
      disorders. Twin and adoption studies have shown that most psychiatric disorders
      have a genetic component, yet very few genetic factors are known, as is true for
      most disorders with a complex genetic origin. Here I review, for nongeneticists,
      some of the basic terminology and concepts used when studying complex genetic
      diseases, with examples from psychiatric genetics. This review is intended to
      help in the understanding and critical evaluation of reports on genetics of
      psychiatric illnesses in the literature.

PMID- 10088043
TI  - Gene chips and arrays revealed: a primer on their power and their uses.
AB  - This article provides an overview and general explanation of the rapidly
      developing area of gene chips and expression array technology. These are methods
      targeted at allowing the simultaneous study of thousands of genes or messenger
      RNAs under various physiological and pathological states. Their technical basis
      grows from the Human Genome Project. Both methods place DNA strands on glass
      computer chips (or microscope slides). Expression arrays start with complementary
      DNA (cDNA) clones derived from the EST data base, whereas Gene Chips synthesize
      oligonucleotides directly on the chip itself. Both are analyzed using image
      analysis systems, are capable of reading values from two different individuals at
      any one site, and can yield quantitative data for thousands of genes or mRNAs per
      slide. These methods promise to revolutionize molecular biology, cell biology,
      neuroscience and psychiatry. It is likely that this technology will radically
      open up our ability to study the actions and structure of the multiple genes
      involved in the complex genetics of brain disorders.

PMID- 10088044
TI  - Benefits and pitfalls encountered in psychiatric genetic association studies.
AB  - The genetic association strategy is currently being applied to a number of
      psychiatric phenotypes including disease vulnerability, personality variation and
      clinical response to psychotropic drugs. Association studies offer the prospect
      of identification of the specific alleles that confer significant effects on
      clinical phenotype. However, it should be noted that this strategy has additional
      advantages as well as unique drawbacks. In this paper, we review the basic
      methodology utilized in each step of a typical psychiatric genetic association
      study and discuss their potential benefits and pitfalls with particular emphasis
      on the selection of clinical phenotype, the identification of a candidate gene,
      the selection of a candidate variant, clinical data set design, and the
      statistical analysis of association data. With appropriate design and execution,
      it is hoped that the association strategy will prove to be as successful in
      psychiatry as it has proven to be in other branches of medicine.

PMID- 10088045
TI  - Alternative phenotypes for the complex genetics of schizophrenia.
AB  - The complexity of the genetics of schizophrenia has been described by many
      investigators. In the absence of simple Mendelian inheritance, genetic linkage
      has not achieved the definitive results found in other illnesses, where such
      methods have led to the identification of responsible genes. Alternative
      phenotypes for linkage analysis are proposed as one solution to this problem.
      These phenotypes, representative of discrete biological deficits in
      schizophrenia, may more closely reflect the effect of a single gene than the
      illness itself. The Mendelian inheritance of one alternative phenotypes, failure
      to inhibit the P50 auditory evoked response to repeated stimuli, has resulted in
      successful linkage of the deficit to the locus of a candidate gene, the alpha 7
      nicotinic acetylcholine receptor on chromosome 15q14. Further support for this
      linkage has recently been found in families from the NIMH Schizophrenia Genetics
      Initiative, using schizophrenia as the phenotype. Alternative phenotypes based on
      discrete biological deficits in schizophrenia have enhanced power for linkage
      analysis. Such analyses can not only facilitate understanding of the genetic
      transmission of schizophrenia, but they also provide further support for
      neurobiological characterizations of the pathophysiology of schizophrenia;
      however, identification of responsible genetic mutations is necessary before
      definitive conclusions can be reached.

PMID- 10088046
TI  - Genetics and mental disorders. National Institute of Mental Health's Genetics
      Workgroup.

PMID- 10088047
TI  - Aggression and anger-related traits associated with a polymorphism of the
      tryptophan hydroxylase gene.
AB  - BACKGROUND: Central nervous system (CNS) serotonergic activity correlates
      inversely with human aggressive behavior, and individual differences in
      aggressive disposition are at least partially heritable. This study was conducted
      to evaluate the possible association between measures of antagonistic behavior
      and an intronic polymorphism of the gene coding for tryptophan hydroxylase (TPH),
      the rate-limiting enzyme in serotonin biosynthesis. METHODS: Locally recruited
      men and women (n = 251) were genotyped for the A218C polymorphism located in
      intron 7 of the TPH gene. All subjects were administered standard interview and
      questionnaire indices of aggression and anger-related traits of personality; in a
      portion of subjects, CNS serotonergic activity was assessed by
      neuropsychopharmacologic challenge (prolactin response to fenfluramine
      hydrochloride). RESULTS: Persons having any TPH U allele scored significantly
      higher on measures of aggression and tendency to experience unprovoked anger and
      were more likely to report expressing their anger outwardly than individuals
      homozygous for the alternate L allele. In men, but not women, peak prolactin
      response to fenfluramine was also attenuated among subjects having any U allele,
      relative to LL homozygotes. CONCLUSIONS: Individual differences in aggressive
      disposition are associated with an intronic polymorphism of the TPH gene in a
      nonpatient sample of community-derived volunteers.

PMID- 10088048
TI  - No coding variant of the tryptophan hydroxylase gene detected in seasonal
      affective disorder, obsessive-compulsive disorder, anorexia nervosa, and
      alcoholism.
AB  - BACKGROUND: The goal of this study was to evaluate the role of genetic variation
      in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of
      several psychiatric diseases in which altered serotonin function has been
      implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD),
      anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD),
      and alcoholism (Alc). METHODS: Ninety-three percent of the TPH coding sequence
      was screened by polymerase chain reaction single-strand conformation polymorphism
      (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP
      patients and 142 normal volunteers. Also included in the screening were 61 Alc
      randomly selected from a Finnish alcoholic population in which an association of
      a TPH intron 7 polymorphism with suicidality was previously observed.
      Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele
      specific restriction enzyme digestion. Genotyping was then performed in 34
      Finnish alcoholic suicide attempters. RESULTS: A rare silent mutation was
      identified in exon 10 and is designated T1095C. The C1095 allele was found in 1
      OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for
      the variant allele. No association was observed between this TPH T1095C variant
      with either OCD, AN, Alc, or suicidality. CONCLUSION: These results suggest that
      the coding sequence of the TPH gene does not contain abundant variants, and may
      not play a major role in vulnerability to several psychopathologies in which
      reduced serotonin turnover has been implicated.

PMID- 10088049
TI  - No association between D2 dopamine receptor (DRD2) "A" system alleles, or DRD2
      haplotypes, and posttraumatic stress disorder.
AB  - BACKGROUND: Association studies between marker alleles at the D2 dopamine
      receptor gene (DRD2) and various psychiatric illnesses have produced conflicting
      results. Reports of allelic associations were originally made with alcoholism,
      but were then extended to other psychiatric disorders, including posttraumatic
      stress disorder (PTSD). METHODS: We studied allele frequency of the DRD2 TaqI
      "A," "B," and "D" system markers in 52 European-American subjects with diagnoses
      of PTSD (based on structured interviews). RESULTS: Frequency of the A1 allele in
      this sample was .15, not significantly different from the .19 allele frequency
      seen in 87 control subjects. We were thus unable to replicate the previous
      reports of allelic association between the DRD2 TaqI "A1" allele and PTSD. There
      were also no significant differences in allele frequency for the "B" or "D"
      systems. We then computed three marker (TaqI "A," "B," and "D" system) haplotypes
      for the sample; DRD2 haplotype frequencies also did not differ between control
      subjects and subjects with PTSD. CONCLUSIONS: We conclude that DRD2 alleles are
      not associated with PTSD in this sample, and that genetic variation at the DRD2
      locus is not likely to be an important contributor to risk for this disorder.

PMID- 10088050
TI  - Family psychiatric history, cerebrospinal fluid monoamine metabolites, and
      temperament in infants.
AB  - BACKGROUND: Variations in cerebrospinal fluid (CSF) levels of the monoamine
      metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, and
      homovanillic acid have been associated with behavioral abnormalities in nonhuman
      primates, and with psychopathology in studies of children and adults. METHODS: We
      assayed monoamine metabolites in "left-over" spinal fluid from 167 neurologically
      normal newborn infants (0-3 months of age), and later (at age 18-21 months of
      age) obtained their family psychiatric histories and assessed their temperament
      using the Colorado Childhood Temperament Inventory (CCTI). RESULTS: Family
      history of antisocial personality disorder predicted significantly lower scores
      for soothability (p = .003) at 18-21 months. There were no statistically
      significant associations between newborn monoamine metabolite levels and any
      aspect of temperament on the CCTI. CONCLUSIONS: These findings suggest complex
      relationships between genetic liability for psychiatric disorders and CSF
      monoamine metabolite levels; those relationships do not seem to be mediated by
      infant temperament. It appears likely that interindividual differences in
      monoamine metabolite levels change over the course of development in humans.

PMID- 10088051
TI  - Apolipoprotein E epsilon 4, other risk factors, and course of Alzheimer's
      disease.
AB  - BACKGROUND: The epsilon 4 allele of apolipoprotein E (apoE epsilon 4) is
      associated with late-onset Alzheimer's disease (AD), but its relationship to
      various aspects of AD has become increasingly unclear. We studied the
      relationship of apoE genotype in AD to educational attainment, history of heart
      disease or head injury, age of onset, gender, severity of illness, depression,
      psychotic symptoms, rate of dementia progression, and time from initial
      evaluation to nursing home placement. METHODS: ApoE epsilon 4 genotype was
      determined for 97 clinically diagnosed AD patients and 61 neuropathologically
      confirmed cases of AD. RESULTS: Presence of one or more epsilon 4 alleles
      occurred in 66% of AD cases as compared with 27% in control subjects (allele
      frequency was .40 for AD, .15 for control subjects). Among AD subjects there was
      no significant relationship between epsilon 4 alleles and educational attainment,
      history of heart disease, head injury, age of onset, severity of illness,
      depression, history of depression, rate of dementia progression, or time to
      nursing home placement. Marginal correlations emerged between number of epsilon 4
      alleles, and delusions (p = .05) and hallucinations (p = .05). There was a trend
      toward increased epsilon 4 homozygosity in patients with onset between ages 65
      and 70 years. CONCLUSIONS: We did not find that individuals with one or two apoE
      epsilon 4 alleles differed significantly in clinical course of AD from those
      without epsilon 4 except for a trend toward increased psychotic symptoms in the
      group as a whole and an increase in epsilon 4 homozygosity in patients with
      reported symptom onset in the late 60s.

PMID- 10088052
TI  - Neuropsychological performance of monozygotic twins discordant for bipolar
      disorder.
AB  - BACKGROUND: A paradigm that involves cognitive assessment of monozygotic (MZ)
      twins discordant for a neuropsychiatric disorder (here bipolar illness) allows
      for the examination of both disease-specific impairments (in the comparison of
      affected to unaffected twins) and risk factors (in the comparison of unaffected
      twins to normal twins). METHODS: Neuropsychological functions were evaluated in
      seven MZ twin pairs discordant for bipolar illness and seven pairs of normal MZ
      twins in an attempt to highlight cognitive abilities associated with
      manifestations of disease and genetic risk factors. At the time of testing, 3 of
      the affected twins were euthymic, 2 had depressive symptoms, and 2 had manic
      symptoms; all were receiving medication. All twins receive neuropsychological
      tests to evaluate intelligence, attention, visuospatial skills, language,
      learning and memory, and problem solving. RESULTS: Statistical analyses revealed
      that the affected twins were significantly impaired as compared to the unaffected
      (and normal) twins on some measures of visuospatial functioning and some verbal
      memory measures. In contrast to a sample of MZ twins discordant for schizophrenia
      studied previously, the cognitive impairments we observed in bipolar twins were
      mild in nature and fairly circumscribed. The unaffected twins performed
      significantly worse than normal controls on a Brown-Petersen memory task, verbal
      list learning, and overall Wechsler Memory Quotient. CONCLUSIONS: These data
      suggest that while some visuospatial deficits and verbal memory deficits may be
      features of bipolar disorder related to disease parameters, mild attenuations in
      overall memory or retrieval function may be related to genetic factors associated
      with the illness.

PMID- 10088053
TI  - Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors
      and the serotonin transporter in the level of response to alcohol: a pilot study.
AB  - BACKGROUND: The vulnerability to alcohol dependence appears to be genetically
      influenced through a variety of mechanisms. One potentially genetically mediated
      channel may be a low level of response (LR) to alcohol, which has been seen in
      children of alcoholics and noted to predict future alcohol abuse and dependence.
      This pilot study uses a case and control genetic association approach to evaluate
      the possible role of five genotypes in both LR and alcoholism in informative
      subgroups of men with high and low LR scores documented 15 years earlier.
      METHODS: As part of a larger study, 41 men, about 39 years old, were selected
      from among the first 113, completed 15-year follow-ups in a prospective study.
      The 17 subjects whose LRs at age 20 were in the lower third were compared on five
      polymorphisms of four genes with 24 men whose reactions to alcohol had been above
      the median. RESULTS: The 14 men with the LL genotype of the serotonin transporter
      (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GABAA alpha 6
      polymorphism had demonstrated lower LR scores at about age 20, and had
      significantly higher proportions of alcoholics than the other genotypes for those
      loci. All four subjects with combined LL and Pro/Ser genotypes had developed
      alcoholism and demonstrated the lowest LR scores overall. There was no evidence
      that two polymorphisms of the 5-HT2A receptor gene and one of the 5-HT2C receptor
      gene were related to LR or alcoholism in this sample. CONCLUSIONS: These results
      are consistent with animal and human studies suggesting a possible role for
      genetic variation in the GABAA alpha 6 and the serotonin transporter in the
      reaction to alcohol and the alcoholism risk.

PMID- 10088054
TI  - DAT1 gene polymorphism in alcoholism: a family-based association study.
AB  - BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of
      the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol
      dependent probands--and in particular those with severe withdrawal symptoms
      (seizures and/or delirium)--compared to nonalcoholics. METHODS: To avoid
      stratification effects, the family-based association approach of Falk and
      Rubinstein was used in our sample of 87 alcohol-dependent probands and their
      biological parents. RESULTS: By applying a family-based association approach, we
      were not able to detect significant association between allele 9 at DAT1 (SLC6A3)
      and alcoholism as well as between patients with or without severe withdrawal
      symptoms. CONCLUSIONS: Based on our data, the impact of the 9-repeat allele of
      the dopamine transporter gene in alcoholism and the severity of alcohol
      withdrawal symptoms is putatively not substantial.

PMID- 10088055
TI  - Triplets with schizophrenia.

PMID- 10088056
TI  - The Collaborative Normal-Tension Glaucoma Study and some of its lessons.

PMID- 10088057
TI  - Photorefractive keratectomy with an ablatable mask and rail system for
      simultaneous correction of myopia and astigmatism: preliminary results.
AB  - BACKGROUND: Alternative methods to correct myopic astigmatism with excimer laser
      surgery are being examined in an attempt to increase efficacy and reliability.
      One approach that is developing interest is the incorporation of a
      polymethylmethacrylate mask into the laser procedure. We examined the efficacy
      and safety of the Summit Apex Plus laser using a new ablatable mask and rail
      system. METHODS: Retrospective study based on follow-up of patients at 1 month
      (59 eyes), 3 months (37 eyes) and 6 months (24 eyes) at an eye laser centre in
      southern Ontario. Patients were recruited from 19 ophthalmic practices located
      primarily in the Niagara region and in western New York. Selected patients with
      naturally occurring myopia and astigmatism were treated with the Summit Apex Plus
      laser with the mask and rail system. Patients were evaluated for changes in
      refraction and visual acuity, and complications (including glare, haloes, haze
      and lines lost of best corrected visual acuity) were assessed. We calculated the
      surgically induced refractive change using the Holladay 10-step method. RESULTS:
      At 6 months the average residual sphere for the low myopia group (-7.00 dioptres
      or less) was -0.60 D and for the high myopia group (greater than -7.00 D) -0.61
      D. This result was found to be both stable and accurate over the follow-up
      period. The cylinder component was reduced irrespective of the amount of
      preoperative myopia. Vector analysis showed that in most patients the correction
      of astigmatism was accurate, although slight undercorrection was observed.
      Complications were minimal, with few residual adverse effects at 6 months.
      INTERPRETATION: We found the mask and rail technique to be both effective and
      safe. Refractive change was stable and accurate, although astigmatism was
      slightly undercorrected. The procedure resulted in few complications, most of
      which resolved by 6 months.

PMID- 10088058
TI  - Neurologic abnormalities associated with persistent hyperplastic primary
      vitreous.
AB  - BACKGROUND: Persistent hyperplastic primary vitreous (PHPV) is usually a
      unilateral ocular abnormality not associated with other systemic findings. We
      describe 16 patients, 7 with unilateral and 9 with bilateral PHPV, in whom
      significant neurologic abnormalities were identified. METHODS: The clinical
      records of 16 children referred to the Visually Impaired Program at a university
      affiliated children's hospital in Vancouver were studied from 1970 to 1996.
      Further investigations, including electroencephalography, computed tomography and
      pediatric neurologic evaluation, were performed to ascertain neurologic deficits.
      RESULTS: Neurologic abnormalities were identified in three of the children with
      unilateral PHPV (hemiparesis, impaired coordination and homonymous hemianopia)
      and seven of the children with bilateral PHPV (ataxia, impaired coordination,
      hypotonia, spastic quadriplegia, microcephaly and deafness). INTERPRETATION: The
      possibility of underlying neurologic abnormality should be considered in patients
      with PHPV, particularly those with bilateral disease. Referral to a pediatric
      neurologist may be appropriate.

PMID- 10088059
TI  - Management of posterior segment intraocular foreign bodies: 14 years' experience.
AB  - BACKGROUND: Penetrating ocular injuries with retained posterior segment foreign
      bodies are challenging cases requiring urgent attention by vitreoretinal
      surgeons. Posteriorly located injuries can result in serious immediate and
      delayed vitreoretinal sequelae, such as retinal detachment and endophthalmitis.
      We report our experience with posterior segment intraocular foreign bodies.
      METHODS: We reviewed the records of all patients with penetrating ocular injury
      with retained intraocular foreign bodies treated at a university-based referral
      practice in Toronto between April 1981 and December 1995. We noted the pre- and
      postoperative Snellen visual acuity, type and volume of foreign body, diagnostic
      technique, surgical management, and pre- and postoperative complications.
      RESULTS: Forty-one patients (all male with a mean age of 38 [range 8 to 78]
      years) were treated during the study period. The length of follow-up ranged from
      1 to 118 (mean 20) months. Eighteen patients (44%) experienced a delay in
      diagnosis or management, or both, of 1 day to 3 years. The rates of retinal
      detachment and endophthalmitis were 41% (17/41) and 17% (7/41) respectively;
      culture gave positive results in 5 cases. Two of the eyes required enucleation. A
      final visual acuity of 6/60 or better was obtained in 33 eyes (80%) and of 6/12
      or better in 21 eyes (51%). Multiple linear regression analysis showed that only
      immediate retinal detachment and the presence of a relative afferent pupillary
      defect had a significant independent effect on final visual acuity. In our
      previous series (1971-81) the retinal detachment rate was 14% (4/28), and there
      were no cases of culture-positive endophthalmitis; final visual acuities of 6/60
      or better and of 6/12 or better were obtained in 46% and 32% of the eyes
      respectively. INTERPRETATION: Reasons for the better outcomes in our more recent
      series may include improved localization of posterior segment foreign bodies with
      computed tomography, more frequent intravitreal surgery with improved vitrectomy
      techniques and the use of the intraocular magnet.

PMID- 10088060
TI  - Drilling the synthetic hydroxyapatite orbital implant.

PMID- 10088061
TI  - Postoperative orbital hemorrhage following thrombolysis for acute myocardial
      infarction.

PMID- 10088062
TI  - Branch retinal artery occlusion: angiographic demonstration of increased retinal
      blood flow after external carotid endarterectomy.

PMID- 10088063
TI  - Determining the clinical significance of randomized clinical trials: a review of
      the efficacy of laser photocoagulation.

PMID- 10088064
TI  - Magnetic resonance imaging of musculoskeletal tumors: skeletal and soft tissue
      masses.
AB  - The purpose of this article is to review the MRI characteristics of
      musculoskeletal tumors, including skeletal and soft tissue masses. MRI has become
      the premier imaging modality for the evaluation of musculoskeletal tumors because
      of its excellent soft tissue contrast, its sensitivity to bone marrow and soft
      tissue edema, and its multiple imaging planes. In a substantial subset of cases,
      MRI can provide a diagnosis or a short differential diagnosis, while certain
      tumors have no distinguishing signal characteristics. MRI of musculoskeletal
      tumors can also be challenging, because the MRI appearance of certain lesions can
      be misleading, and a knowledge of the instances in which MRI over- and
      underestimates the malignancy of lesions is invaluable. The importance of correct
      protocols for tumor evaluation, both in diagnosis and in pre-operative
      evaluation, are discussed. Common pitfalls that may over- or underestimate the
      aggresivity of lesions will be highlighted, as will the role of gadolinium
      enhancement in the evaluation of lesions. The MRI appearance of common benign and
      malignant muculoskeletal lesions will be illustrated.

PMID- 10088065
TI  - Spatial extension of local pacing capture in the lateral free wall of the right
      atrium during clinical chronic atrial fibrillation.
AB  - OBJECTIVES: The aims of our study were to define the spatial extension of local
      atrial pacing capture (LAPC) in the right lateral atrial wall and to verify the
      effects of antiarrhythmic drugs on capture extension. BACKGROUND: Recently, LAPC
      during spontaneous chronic atrial fibrillation (AF) has been demonstrated
      directly in humans, but no systematic attempt has been made to evaluate its
      spatial extension. METHODS: The study was conducted in 14 consecutive patients
      with chronic AF, nine of whom were taking antiarrhythmic drugs. A Franz catheter
      for pacing and monophasic action potential recording was positioned in the
      lateral right atrial wall. An octopolar recording lead was positioned about 10 mm
      apart. The presence of atrial capture and its extension (number of captured
      bipolar pairs) were evaluated during decremental pacing. RESULTS: Forty-eight
      atrial capture attempts were made. LAPC was achieved in all the performed
      attempts. The AF types immediately before capture were type 1 in 35 (73%) and
      type 2 in 13 (27%) episodes. In 32 episodes, the capture was lost within 15
      seconds and in the remaining 16 pacing was stopped after 15 seconds of stable
      capture. In 26 episodes, capture extended radially up to 4 cm from the pacing
      site, in 18 up to 3 cm, in 3 up 1 cm and in 1 up 1 cm. The mean extension in
      patients being treated with antiarrhythmic drugs was significantly greater than
      what was seen in untreated patients (3.8 +/- 0.4 vs 2.9 +/- 0.7 cm, p < 0.00001).
      Capture loss was less frequently observed when all four of the bipolar recording
      sites had been captured (13/25, 52% vs 19/23, 82%, respectively, p = 0.05).
      CONCLUSIONS: LAPC in the lateral right atrial wall extends over a radius of 30-40
      mm in the majority of capture episodes and is greater in patients treated with
      antiarrhythmic drugs. Our results suggest that, at least theoretically,
      simultaneous multisite pacing could be used to terminate AF. Moreover, a
      reduction in the atrial defibrillation threshold could be expected performing low
      energy internal cardioversion during LPC.

PMID- 10088066
TI  - Effects of early treatment with captopril and metoprolol singly or together on
      six-month mortality and morbidity after acute myocardial infarction. Results of
      the RIMA (Rimodellamento Infarto Miocardico Acuto) study. The RIMA researchers.
AB  - The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess
      the relative effects of angiotensin-converting enzyme (ACE) inhibition by
      captopril, beta-blocker therapy by metoprolol, and their combination in patients
      with a first acute myocardial infarction on: 1. echocardiographically detected
      left ventricular remodeling; 2. prognosis. The second goal will be the argument
      of the present paper. Two-hundred fifty < or = 75 years consecutive patients
      (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly
      allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1),
      metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3)
      starting in the first 24 hours after the onset of symptoms. Intravenous beta
      blockers in the acute phase of myocardial infarction and all other cardioactive
      drugs were allowed. The effect of the randomized therapy at six months from
      admission to the coronary care unit was considered in relation to: 1. recurrence
      of spontaneous cardiac events and of elective revascularization procedures; 2.
      adverse reactions (hypotension, atrioventricular block, cough, allergy, need of
      beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment
      modification based on physician's decision. RESULTS: Definite follow-up data were
      available in 226 patients and 195/226 patients (86%) had a complete treatment
      period. In these patients (per protocol analysis), 37 spontaneous cardiac events
      occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina
      requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven
      patients received a coronary revascularization procedure. Events occurred in
      11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from
      Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis
      demonstrated an increased odds ratio (OR) for spontaneous cardiac events in
      patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective
      revascularization procedures were statistically less frequent in patients treated
      with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2
      and 3; p = 0.03). The intention-to-treat analysis on the overall population (226
      patients) confirmed the presence of a trend towards a higher risk in patients
      from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were
      observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients
      from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the
      multivariate regression analysis, a trend towards less adverse reactions in
      patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95%
      Cl: 0.15-1.13; p = 0.07). CONCLUSIONS: In a randomized early post-infarction
      treatment strategy, ACE inhibition with captopril alone or in combination with
      metoprolol demonstrated an increased protection against spontaneous cardiac
      events at six months in comparison with metoprolol alone. On the other hand, the
      beta-blocker treatment was associated with a lower number of elective
      revascularization procedures and appeared better tolerated than ACE inhibition.

PMID- 10088067
TI  - Effectiveness of in-ward management of femoral access after invasive procedures
      using large sheaths.
AB  - BACKGROUND: The cost-effectiveness of expensive suture mediation devices for the
      management of femoral access is currently under investigation, while the
      effectiveness of in-ward femoral access management by standard care has not yet
      been assessed. METHODS: To determine whether a logistic model that includes
      management of femoral access by the cardiology ward staff is effective, 945
      consecutive invasive procedures using > or = 8 Fr sheaths were prospectively
      screened over a 6-month study period. Vascular complications included: any need
      for surgical or endovascular repair, ultrasound-guided compression, any femoral
      or iliac bleeding requiring blood transfusion. RESULTS: During the study period
      there were 581 diagnostic procedures, and 364 interventional procedures.
      Interventional procedures included 98 primary PTCA, 42 coronary atherectomies,
      and 39 intraaortic balloon pump supported PTCA. Vascular complication rate was
      1.6% (surgical repair 0.2%, ultrasound-guided compression 1.1%, blood transfusion
      0.3%). CONCLUSIONS: The vascular access management by the cardiology ward staff
      was associated with a very low rate of vascular complications. This policy may
      play a role in reducing costs and improving logistics.

PMID- 10088068
TI  - [The radial artery in coronary surgery: the midterm clinical and angiographic
      results and the variation in vasoreactivity over time].
AB  - OBJECTIVE: To evaluate the mid-term angiographic results of radial artery grafts
      used for myocardial revascularization. METHODS: The first 68 consecutive
      surviving patients who received a radial artery graft proximally anastomosed to
      the aorta at our institution were restudied in a five-year follow-up (mean 59 +/-
      6.5 months); 48 of these patients had already undergone an early angiographic
      examination. The response of the radial artery to the endovascular infusion of
      serotonin was evaluated one and five years after surgery and the mid-term status
      of the radial artery grafts was correlated with the degree of stenosis of the
      target vessel and with the Ca(++)-channel-blocker therapy. RESULTS: The patency
      and perfect patency rates of the radial artery five years after the operation
      were 91.9 and 87.0% respectively. All radial artery grafts that were patent early
      after surgery remained patent at mid-term follow-up and in seven patients early
      parietal irregularities disappeared after five years. The early propensity to
      graft spasm after serotonin challenge decreased markedly at mid-term follow-up.
      The continued use of Ca(++)-antagonists after the first postoperative year did
      not affect the status of the radial artery graft, whereas the severity of target
      vessel stenosis markedly influenced the angiographic results. CONCLUSIONS: The
      mid-term angiographic results of RA grafts used for myocardial revascularization
      are excellent. A correct surgical indication is essential, whereas continued
      therapy with Ca(++)-antagonists after the first year does not influence the mid
      term angiographic results.

PMID- 10088069
TI  - [Myocardial scintigraphy by the gated SPECT method in coronary disease patients
      with postischemic stunning].
AB  - Gated SPECT using Tc-99m-labeled flow tracers provides simultaneous assessment of
      global and regional myocardial perfusion and function. The aim of this study was
      to evaluate whether regional wall thickening (WT) obtained after stress and at
      rest makes it possible to identify and analyze a subgroup of post-ischemic
      stunned patients. METHODS: We studied 20 patients (18 males) who underwent
      conventional diagnostic dual-day stress/rest Gated SPECT following injection of
      925 MBq of 99mTc-tetrofosmin using a dual-head SPECT camera (Vertex ADAC). The
      mean age of these patients was 59 years (38-71) and 10 of them had a history of
      previous acute myocardial infarction (AMI). Perfusion was analyzed on ungated
      images using 20 segments scored on a 5-point scale (0 = normal, 4 = no uptake),
      while WT and motion were assessed visually on stress/rest end-systolic images
      using a 4-point score (0 = normal, 3 = absence of WT/motion). Left ventricular
      ejection fraction (LVEF) and volumes were calculated. All patients underwent
      coronary angiography. RESULTS: All patients showed at least one reversible defect
      with post-stress WT reduction and normal rest WT. The stunned group showed a
      significant post-stress reduction of LVEF and a statistically non-significant
      increase of end systolic volume (ESV). A good correlation was observed between
      global perfusion and WT score both at stress and rest conditions; LVEF showed a
      significant inverse correlation with global post-stress and rest perfusion and WT
      score. ESV and the global perfusion stress/rest score showed a good correlation,
      while end-diastolic volume did not correlate. In 44% of the segments with fixed
      defects, there was a normal WT and normal coronary-related vessel (false
      positives); 28% of reversible segments showed a post-stress pathological WT and
      five of them a rest pathological WT. CONCLUSIONS: The gated SPECT myocardial
      perfusion evaluation allowed us to analyze a subgroup of post-stress stunned
      coronary artery disease patients. The post-stress LVEF reduction in this
      population seems to be due to the increase of end-systolic volume caused by
      endocardial ischemia. The stunned segments showed severe perfusion defects.

PMID- 10088070
TI  - Stenting of a stenotic radial artery coronary graft: a new therapeutic scenario
      in coronary artery disease.
AB  - With the increasing application of arterial coronary revascularization, a number
      of patients may develop arterial graft obstructive disease. In addition, the
      predominantly muscular structure of the radial artery wall may predispose radial
      artery coronary grafts to spasm. For the first time, we describe a case of
      stenting of a stenotic free radial artery graft and discuss the technical and
      pathophysiological aspects of the procedure.

PMID- 10088071
TI  - Dual-chamber pacemaker implantation in a young woman with Ebstein's anomaly.
AB  - A case of 28-year-old woman with Ebstein's anomaly and complete AV block,
      requiring a permanent dual-chamber pacemaker implantation, is described. The
      ventricular lead was successfully placed in the right ventricular outflow tract
      and there was no problem associated with positioning of the atrial electrode in
      the right atrial appendage, with good sensing and threshold. The subsequent
      clinical course was uncomplicated and the patient has remained asymptomatic
      throughout the eight-month follow-up. This experience allows us to state that
      even in the presence of the marked structural abnormalities of Ebstein's anomaly,
      dual-chamber pacing is indeed feasible and successful, enabling the disappearance
      of symptoms related to the AV block.

PMID- 10088072
TI  - [Percutaneous coronary angioplasty in the elderly: a report of 2 cases in
      patients over 90].
AB  - Percutaneous transluminal coronary angioplasty is a validated method for coronary
      revascularization over coronary surgery in elderly patients. We describe two
      cases in patients in their nineties. Case n. 1: a 95-year-old patient with post
      infarction angina that was not controlled well by medical therapy. On admission
      to our department, the patient was in good hemodynamic condition and a
      transthoracic echocardiographic examination confirmed normal left ventricular
      systolic function. Coronary angiography showed a severe calcified stenosis of the
      left anterior descending coronary artery, which was successfully treated with
      coronary angioplasty and stenting. After three months, the patient was readmitted
      because of angina. A new coronary angiogram showed diffuse in-stent restenosis,
      which was successfully treated with rotational atherectomy and angioplasty. The
      patient was asymptomatic at follow-up after 6 months. Case n. 2: a 91-year-old
      patient was admitted for an unstable angina. On admission to our department the
      patient was in good hemodynamic condition. Coronary angiography showed a severe
      stenosis of the left anterior descending coronary artery that was successfully
      treated with angioplasty and stenting. The patient was asymptomatic at 6-month
      follow-up. These cases show that coronary revascularization can successfully be
      performed even in patients in their nineties when medical therapy is unsuccessful
      and the patients are considered at high risk for surgery.

PMID- 10088073
TI  - [Syncopal vasospastic angina in a patient with familial nonobstructive
      hypertrophic cardiomyopathy].
AB  - We describe an unusual case of a 51-year-old woman affected with familial non
      obstructive cardiomyopathy and syncopal vasospastic angina. The use of
      hyperventilation stress-echo testing, recommended by the authors because of its
      simplicity and safety, was decisive in showing the causal role of coronary spasm
      of the left anterior descending artery. The coronarography had not shown
      obstructive lesions of the coronary arteries, but during the procedure the
      patient had refused ergonovine or acetylcholine injections.

PMID- 10088074
TI  - Subacute left ventricular free-wall rupture in early course of acute myocardial
      infarction. Clinical report of two cases and review of the literature.
AB  - Left ventricular free wall rupture (LVFWR) may complicate an acute myocardial
      infarction (AMI); its frequency ranges from 1 to 6 percent. In the era of
      coronary care units, LVFWR is the second cause of in-hospital death, after pump
      failure. The subacute presentation accounts for 2-3 percent of total hospital
      admissions for AMI. Heart rupture may not be suddenly fatal and sometimes there
      is enough time for surgical repair. Electromechanical dissociation is neither the
      only nor the main clinical presentation. More subtle symptoms occurring hours or
      days before the final event include unexplained hypotension and transient
      bradycardia and some ECG features such as persistent ST-segment elevation with T
      waves failing to invert in the same leads. On echocardiographic subcostal view,
      pericardial effusion of more than 5-10 mm, with echo-dense masses overlying the
      heart independently of cardiac tamponade, is highly suggestive of heart rupture.
      If pericardiocentesis yields hemorrhagic fluid, surgical intervention is
      mandatory, providing both diagnostic confirmation and definitive treatment.
      Medical management strategies (prolonged bed rest, beta-blockade therapy) are
      still experimental but could become suitable for particular subsets of patients
      (elderly patients and patients at a high surgical risk). We report two cases of
      subacute LVFWR and review the currently available literature.

PMID- 10088075
TI  - [The treatment of familial hypercholesterolemia and of the dyslipidemias
      responsible for cardiovascular disease].

PMID- 10088076
TI  - Beyond morphology: new coronary physiologic approaches to interventions.

PMID- 10088077
TI  - [The embolic risk and oral anticoagulant therapy in chronic heart failure].

PMID- 10088078
TI  - [The assessment of the thromboembolic risk and the role of antithrombotic
      prophylaxis in nonrheumatic atrial fibrillation].

PMID- 10088079
TI  - Exercise capacity and skeletal muscle myosin heavy chains in CHF.

PMID- 10088081
TI  - [To be or not to be].

PMID- 10088080
TI  - Right coronary artery aneurysm simulating right intraatrial mass.

PMID- 10088082
TI  - Practice standards and clinical competence.

PMID- 10088083
TI  - What is your diagnosis? Laryngeal lymphosarcoma.

PMID- 10088084
TI  - Short form of Demodex species mite in the dog: occurrence and measurements.
AB  - A form of Demodex species mite shorter in length than Demodex canis was found in
      six consecutive cases of canine demodicosis. The mean length of the parasite was
      122.6 microns (SD 12.0 microns, 39 mites counted), significantly shorter than
      either male or female forms of D canis (P < 0.0001). The proportion of short to
      long mites in each case varied from 0.5 to 22 per 100. In young dogs, skin signs
      associated with the presence of mites were first noted after about seven months,
      while in the oldest subject the disease became apparent at 10 years of age. This
      form of mite has now been found in four countries over three continents, the
      findings suggesting that it is not uncommon and is acquired in puppyhood,
      although it may be carried unnoticed for many years.

PMID- 10088085
TI  - Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in
      the cat.
AB  - Twenty-three cats with stable chronic renal failure (CRF) were examined in a
      prospective study of the effects of feeding a veterinary diet restricted in
      phosphorus and protein with or without an intestinal phosphate binding agent
      (aluminium hydroxide) on plasma phosphate and parathyroid hormone (PTH)
      concentrations. Fifteen cats accepted the veterinary diet; compliance was not
      achieved in the remaining eight (due to limited intake by the cats or owner
      resistance to diet change). Feeding the veterinary diet was associated with a
      significant fall in plasma phosphate and PTH concentrations by five months, with
      only two cats requiring aluminium hydroxide therapy. The maximum decrease in
      plasma PTH concentration was not associated with a significant change in plasma
      1,25 dihydroxycholecalciferol concentration. Euparathyroidism was achieved in
      eight cats. Conversely, in cats with CRF fed proprietary diets over the same time
      period, mean plasma PTH concentrations did not change significantly; indeed, in
      seven of the eight cats, PTH concentrations increased. Dietary therapy alone or
      in combination with intestinal phosphate binders does reduce PTH concentrations
      in cats with CRF and, when effective control of phosphate intake is achieved,
      plasma PTH can be normalised.

PMID- 10088086
TI  - Evaluation of serum free thyroxine and thyrotropin concentrations in the
      diagnosis of canine hypothyroidism.
AB  - Canine thyroid-stimulating hormone (cTSH), total thyroxine (T4) and free T4 by
      equilibrium dialysis (fT4d) were measured in serum samples from 107 dogs with
      clinical signs suggestive of hypothyroidism in which the diagnosis was either
      confirmed (n = 30) or excluded (n = 77) by exogenous TSH response testing. Median
      serum total T4 and fT4d concentrations were significantly lower and cTSH
      significantly higher (P < 0.001) in hypothyroid compared with euthyroid dogs.
      Differential positive rate analysis determined optimal cut-off values of less
      than 14.9 nmol/litre (total T4), less than 5.42 pmol/litre (fT4d), greater than
      0.68 ng/ml (cTSH), less than 17.3 (T4 to cTSH ratio), and less than 7.5 (fT4d to
      cTSH ratio) for hypothyroidism. These had a sensitivity and specificity of 100
      and 75.3 per cent, 80 and 93.5 per cent, 86.7 and 81.8 per cent, 86.7 and 92.2
      per cent, and 80 and 97.4 per cent, respectively, for diagnosing hypothyroidism.
      Corresponding areas under the receiver operating characteristic curves were 0.92,
      0.93, 0.87, 0.93 and 0.93. Unexpectedly low cTSH values in hypothyroid dogs may
      have resulted from concurrent non-thyroidal illness. Unexpectedly high serum cTSH
      values in the euthyroid dogs might have resulted from recovery from illness or
      concurrent potentiated sulphonamide therapy. Measurement of endogenous cTSH
      concentration is a valuable diagnostic tool for canine hypothyroidism if used in
      association with assessment of T4. Estimation of fT4d added only limited
      additional information over total T4 measurement.

PMID- 10088087
TI  - Oesophageal squamous cell carcinoma in two cats.
AB  - Two cases of feline oesophageal squamous cell carcinoma are described. In both
      cases, diagnosis was achieved by radiography, endoscopy and cytology, and later
      confirmed by histology. One cat underwent oesophagectomy followed by end-to-end
      anastomosis, but died three days postsurgery; the second cat was euthanased after
      diagnosis.

PMID- 10088088
TI  - Management of a proximal pelvic limb skin laceration in a dog using a skin flap
      and an external fixator.
AB  - A nine-year-old, spayed female crossbred dog sustained a traumatic skin lesion to
      the right proximal pelvic limb, extending to the extensor surface of the stifle.
      Surgical management of the wound included primary closure using a body skin flap
      fashioned from the right caudolateral abdominal wall. To achieve closure and
      prevent tension on the wound, the coxofemoral and stifle joints on the affected
      side needed to be immobilised in flexion. Flexion immobilisation of the stifle
      was achieved using the anatomical principle of muscle reciprocation. The
      ipsilateral tarsal joint was immobilised in flexion using a uniplanar-bilateral
      (type II) transarticular external skeletal fixator and this resulted in the
      automatic flexion of the stifle. The fixator was removed six weeks
      postoperatively when the wound had healed. There were no apparent complications
      associated with the fixator either during its use or in the longer term following
      its removal.

PMID- 10088089
TI  - Pulmonary embolism and cor pulmonale in a cat.
AB  - A 14-year-old male neutered cat experienced pulmonary embolism 15 days following
      surgical debridement of a recurrent dorsolumbar abscess. Clinical signs were
      dominated by respiratory distress. Pulmonary embolism was suggested from the
      lateral thoracic radiograph by the presence of an abruptly attenuated lobar
      artery and a contiguous oligaemic area in the caudal lung lobe. Pulmonary
      hypertension was demonstrated on Doppler echocardiography by right pulmonary
      artery dilation and tricuspid regurgitation raising the pulmonary arterial
      pressure to 56 mmHg. Chronic pulmonary hypertension, assumed from right
      ventricular wall hypertrophy, and hypokinesia, indicating chronic cor pulmonale,
      was suggestive of chronic rather than acute pulmonary embolism. Postmortem
      histological evidence of pulmonary arteriolar occlusion confirmed the diagnosis
      of pulmonary embolism.

PMID- 10088090
TI  - Perineal hernia with bladder retroflexion in a female cocker spaniel.
AB  - Perineal herniation in the bitch is rare and its complication by bladder
      retroflexion in the bitch has not been previously reported in the literature.
      This case report describes a multigravid, five-year-old female cocker spaniel
      with bilateral perineal hernias, complicated by marked rectal sacculation and
      ventral bladder retroflexion. The case was managed initially by cystopexy and
      colopexy, followed seven days later by bilateral perineal herniorrhaphy. There
      was no recurrence of the problem by 12 months postsurgery.

PMID- 10088091
TI  - Two new manuals--on emergency medicine, and anaesthesia.

PMID- 10088092
TI  - [Humanism and development].

PMID- 10088093
TI  - [Systems of geographic information and the campaign against tropical diseases].

PMID- 10088094
TI  - [Image...vertebral hydatidosis].

PMID- 10088095
TI  - [Rifampicin].

PMID- 10088096
TI  - [Diagnosis of pruritus in a traveller].

PMID- 10088097
TI  - [Burkina Faso--a multitude of public health emergencies].

PMID- 10088098
TI  - [Emergency medicine and resuscitation in a tropical environment-- a new challenge
      for Africa].

PMID- 10088099
TI  - [Impregnated mosquitoes and malaria].

PMID- 10088100
TI  - [Perineal gangrene: report of 30 cases observed at Abidjan].
AB  - Perineal gangrene may be classified as primary, e.g. Fournier's gangrene of the
      external genitals, or secondary due to locoregional injury. Perineal gangrene is
      still a topic of interest in tropical zones where mortality remains high despite
      current therapeutic modalities. The purpose of this retrospective study was to
      analyze etiologic, bacteriologic, and therapeutic data in 30 cases observed over
      a one-year period in a surgical setting in the Ivory Coast. There were 26 men and
      4 women with a mean age of 43 years. All were treated by extensive removal of
      necrotic tissue in association with antimicrobial therapy for the likeliest agent
      and appropriate supportive measures. Colostomy was performed in 6 cases and
      drainage of the urinary tract was required in 11 cases. Anti-tetanus treatment
      was administered in all cases. Thirteen patients were HIV-positive, five were
      diabetic, and two presented chronic renal insufficiency. Perineal gangrene was
      classified as secondary in 17 cases and primary (Fournier's gangrene) in 13
      cases. Bacteriologic study of puss and tissue specimens collected from necrotic
      areas demonstrated a mixed population of microbial organisms predominated by
      streptococcus A (n = 19) and Escherichia coli (n = 13). Positive diagnostic
      results were obtained in 5 of 20 hemocultures and in 8 of 11 cystobacteriologic
      tests. Eight patients died and nine presented complications including necrosis of
      the testicles, atrophy of the testicles, shock, and coma. Healing was obtained
      without skin grafting in 22 survival cases but 5 of them required secondary
      suturing. The mean duration of hospitalization was 45 days. In our experience,
      perineal gangrene led to severe consequences despite adequate management
      especially in HIV-infected patients. The treatment of choice is still extensive
      emergency surgical removal (repeated, if necessary) of necrotic tissue in
      association with adequate supportive measures and wide spectrum antimicrobial
      therapy.

PMID- 10088101
TI  - [Sexual abuse in children in Cameroon].
AB  - The purpose of this study was to determine the incidence and socio-demographic
      features of child sexual abuse in an African setting. The files of 5082 children
      seen between August 1, 1992 and July 31, 1997 at the Center for Mother and Child
      Protection in Yaounde, Cameroon, were retrospectively reviewed. Sexual abuse was
      recognized in a cohort of 104 children of both sexes. The incidence of sexual
      abuse in the studied population was 2.05%. The victims were more often girls than
      boys: 95.2% vs 4.8%. Assault usually occurred during prepuberty (41.4%) and
      puberty (20.2%). However a non-negligible number of cases, all involving girls,
      occurred before the age of 10 years (29.8%). Assaults by women occurred but were
      uncommon (7.8%). Rape was the most frequent form of abuse (97.1%). About 25% of
      cases occurred within the family. These findings confirm the existence and
      incidence of child sexual abuse in an African setting and raise the taboo on the
      absolute phallocratic power of fathers and uncles over young girls and women in
      general. This study also provides new evidence of the vulnerability of women in
      Africa as a result of their traditional status in society.

PMID- 10088102
TI  - [Use of a questionnaire for quick identification of the principal foci of urinary
      bilharziasis in central Ivory Coast].
AB  - Simple questionnaires designed for use in schools have been used to identify
      communities at high risk for urinary schistosomiasis in several African countries
      but not in the Cote d'Ivoire. The primary purpose of this study was to assess the
      acceptance and feasibility of the school questionnaire approach in the Cote
      d'Ivoire. Questionnaires were distributed to 136 schools in central Cote
      d'Ivoire. Responses were obtained within 6 weeks from 124 schools (91.2%). A
      total of 12,479 school children were interviewed. At 60 schools, reagent stick
      tests were performed within two weeks to detect microhematuria by trained
      teachers. A biomedical team was sent to 14 selected schools to check results by
      reagent stick testing and urine filtration. Reagent stick tests showed high
      specificity (97%) and moderate sensitivity (67%). A strong statistical
      correlation was observed between responses to two key questions concerning "blood
      in urine" and "having had schistosomiasis" and the results of reagent stick
      testing (Spearman rank correlation, p < 0.0001). Our findings are in good
      agreement with previous reports. Using the data obtained, we were able to
      accurately map the distribution of urinary schistosomiasis in the study area. Use
      of this questionnaire for quick identification of high risk communities for
      urinary schistosomiasis was recommended as a preliminary step in the planned
      national control program and should allow better targeted of scarce resources.

PMID- 10088103
TI  - [Drug resistance of Plasmodium falciparum along the borders of the highlands in
      Madagascar: outlook for a national control program].
AB  - Resistance of Plasmodium falciparum to chloroquine was first suspected in
      Madagascar in 1975 and later confirmed in vivo and in vitro. During the period
      from 1985 and 1990, the network of public health monitoring stations reported
      that 1% of the population living on the central Highlands of Madagascar died of
      malaria. Thereafter the National Malaria Control Program achieved good success by
      spraying homes with insecticide and reorganizing distribution of chloroquine in
      all villages. However data recorded between 1996 and 1998 indicates that, after
      four years of widespread chloroquine use, resistance to amino-4-quinolones is
      progressing in Madagascar. The tests described in this report were performed on
      patients with documented malaria included in cohorts and followed year round by a
      physician. The three villages studied were located along the borders of the
      highlands between the plateaus and coastal areas. In vivo tests showed that the
      incidence of chloroquine resistance was 0% in Mahakary, 32% in Ankazobe and 30%
      in Saharivo. Clinically, however, treatment was unsuccessful in only 16% and 8%
      of cases respectively. In vitro tests demonstrated chloroquine sensitivity in 79%
      of the 153 strains tested. No resistance to quinine or halofantrine was observed.
      In vitro tests indicated an onset of resistance to mefloquine. Although the
      success rate of chloroquine treatment is nearly 80%, spread of strongly
      chloroquine-resistant strains is a risk especially in subjects with mild immunity
      to malaria.

PMID- 10088104
TI  - [Hypertensive effects of qat].
AB  - Chewing of Qat leaves which contain amphetamine alkaloids is a traditional drug
      practice in the horn of Africa. Cathine and cathinone are responsible for the
      desired psychogenic (suppression of hunger, mind stimulation, euphoria) and
      sympathicomimetic effects. In this study, we monitored seven volunteers during a
      traditional qat ritual. An increase in systolic and diastolic pressure was
      observed in three patients including one presenting predisposing chronic arterial
      hypertension. Peak pressure was observed approximately seven hours after
      beginning the ritual. The three patients presenting pressure changes were not
      significantly different from the four unaffected patients with regard to age or
      duration of qat use. These findings suggest that qat use by untreated
      hypertensive patients who react strongly to vasoconstrictive effects can lead to
      hypertension and resulting cardiovascular complications.

PMID- 10088105
TI  - [A case of cross infection by Onchocerca volvulus and Onchocerca ochengi in
      Simulium damnosum S.L].
AB  - During a routine entomological survey conducted within the framework of the
      Program to Control Onchocerciasis in West Africa, a female simulium forest fly
      was found to be contaminated by 13 Onchocerca volvulus larvae and 7 Onchocerca
      ochengi larvae. The two Onchocerca species were identified using specific DNA
      probes. We speculate that cross infection could be related either to behavioral
      factors, e.g. interruption of blood meals on two different hosts, or
      developmental factors, e.g. asynchronous development of parasites of the same
      species or specific differences in the duration of parasite cycles. Further study
      will be needed to determine the incidence and scope of cross infection in areas
      where accurate assessment of the impact of vector control on transmission of
      onchocerciasis in man is required.

PMID- 10088106
TI  - [Intracranial subdural hematoma during spinal anesthesia].
AB  - Spinal anesthesia (SA) is frequently used in tropical zones. Intracranial
      subdural hematoma is an uncommon complication of SA. The purpose of this report
      was to describe a case of intracranial subdural hematoma observed during SA
      performed for cesarean section in a 22-year-old women in Senegal. After one month
      of persistent intense headache, diagnosis was confirmed by computerized
      tomography. The hematoma was successfully treated by drainage under general
      anesthesia. Intracranial subdural hematoma has been attributed to cerebrospinal
      fluid hypotension due to leakage through the dural puncture site. Diagnosis,
      which may be difficult in Africa, should be suspected in patients with persistent
      headaches after SA. Confirmation requires computerized tomography of the brain.
      Prevention of this complication depends on the use of fine beveled-tipped
      puncture needle which are rarely available in the African setting.

PMID- 10088107
TI  - [Difficulties in the management of supracondylar fractures of the humerus in
      children living in Central African Republic].
AB  - Like many developing countries, the Central African Republic lacks the technology
      and skills to perform certain medical procedures. One example of this situation
      can be found in the Pediatric Surgery Department of Bangui with regard to first
      intention management of supracondylar fractures of the humerus (SCF). Due to a
      lack of proper technological facilities (e.g. absence of brightness enhancement)
      and to insufficient staff training, management of SCF must be limited to
      orthopedic reduction followed cast application and brachio-anti-brachio-palmar
      traction such problems. This retrospective study describes management of 119
      cases of SCF involving children between the ages of 0 and 15 years. Special
      emphasis was placed on factors impairing outcome, namely, inadequate staff
      training, availability of brightness enhancement, and poor awareness on the part
      of the parents concerning the seriousness of SCF. The quality of reduction was
      compared according to whether reduction was done with or without brightness
      enhancement (reduction without brightness enhancement was imperfect in most
      cases: 78/119) and according to fracture grade (high number of imperfect
      reductions in grade 3 and 4:69%). Assessment of outcome at one month showed a
      high incidence of poor results due to severe fracture or imperfect reduction. A
      prospective study including 35 cases with a follow-up of three years showed poor
      results for the same reasons. Comparison of these results with those reported by
      previous authors showed a large gap which must be filled by upgrading technical
      facilities and training staff.

PMID- 10088108
TI  - [Guidelines for evaluating the viability of health care centers: test in northern
      Cameroon].
AB  - A working group has developed a manual of practical guidelines for evaluating the
      viability of health care centers (HCC). These guidelines were tested in 1996 at
      the HCC in Badjouma, Cameroon. Viability is assessed in three dimensions, i.e.
      quality of care, cost-effectiveness, and institutional efficacy on the basis of
      the demand for services, staff requirements, cash flow, and supply costs. Regular
      evaluation of these parameters allows identification of areas requiring
      improvement to enhance the viability of the HCC. With only 0.29 visits per year
      per inhabitant, the attendance rate at the Badjouma facility is low. Public
      appeal is adversely affected by an under-qualified staff and poor equipment.
      Overall operating expenses are 6.8 million CFA francs per year and depreciation
      costs are 1.7 million CFA francs per year. Direct proceeds related to health care
      services (mainly sale of medication) are 4.1 million CFA francs. The remaining
      sources of revenue are state subsidies (2.5 million CFA francs) and international
      aid (0.4 million CFA francs). The deficit is 1.5 million CFA francs corresponding
      mainly to depreciation costs. Evaluation of the financial viability based on
      service-generated revenues alone (49%) and on combined domestic revenues, i.e.
      service revenues and state subsidies (79%), shows that the HCC depends mainly on
      depreciation costs. Analysis of institutional efficacy by comparing real activity
      with activity defined in official texts showed that the state was the main
      decision-maker but also revealed a tendency to pass off responsibility due to
      poorly defined command structure. The results of this test validate the proposed
      manual as a tool for global analysis of the activity and relevance of a HCC.
      Findings can be used to draw conclusions on the effects of national health
      policies at the local level.

PMID- 10088109
TI  - [The campaign against onchocerciasis in Africa: update].
AB  - Two methods are being used to control onchocerciasis. The first has a delayed
      effect and consists in reducing or interrupting transmission of Onchocerca
      volvulus by eradication of the vector at its most vulnerable developmental stage,
      i.e. the larval stage. The second method has more immediate effects and consists
      in mass treatment using ivermectin, the only widely available drug, to reduce the
      density of microfilariae (the pathogenic stage of the parasite) in the
      population. Both strategies have been implemented within the framework of two
      international programs: the Onchocerciasis Control Program (OCP) in West Africa,
      which started in 1974 and will continue until the end of 2002, and the African
      Program for Onchocerciasis Control (APOC), which was launched in 1995 and will
      last for 12 years. This article presents an overview of the efficacy of available
      control tools, as well as the objectives, strategies, organization, and results
      of the two ongoing control programs. Also dealt with are future perspectives of
      onchocerciasis control including monitoring techniques to maintain OCP gains, and
      research to develop new control tools and optimize the program efficacy.

PMID- 10088110
TI  - [Tropical myositis].
AB  - Tropical pyomyositis (TP) is a microbial infection involving one or more skeletal
      muscles that rapidly leads to abscess. The most common infectious agent is
      Staphylococcus aureus. Since muscle tissue is highly resistant to infection,
      occurrence of TP is contingent upon one or more compromising factors such as
      trauma, skin lesions, parasitosis, or malnutrition. HIV infection is currently a
      major factor in the occurrence of TP. While Staphylococcus aureus accounts for
      80% of cases, other microbial agents have been identified including gram-positive
      cocci and gram-negative bacilli. TP is endemic in intertropical zones of Africa
      and Latin America and in island areas of the Pacific Ocean. However a growing
      number of non-tropical cases have been reported in association with AIDS. The
      most frequent presentation is single-muscle involvement in the thighs, calves,
      and buttocks. The symptomatic phase or suppurative phase is almost always
      associated with hyperthermia. The infected muscle indurates prior to development
      of characteristic fluctuance. Hemocultures are seldom positive but needle
      aspiration may confirm diagnosis. Ultrasound imaging can allow early detection.
      Severe sepsis or cardiovascular, renal, or pleuropulmonary complications are
      observed in 10% of cases. Treatment is antibiotic therapy with penicillin M and
      surgical drainage or needle puncture of abscess cavities. Prognosis is generally
      favorable even in HIV-infected patients.

PMID- 10088111
TI  - [Blood transfusion in Ethiopia].
AB  - Nearly 30,000 bags of blood are collected per year in Ethiopia for a population
      of 56 million people. Eighty percent of this volume is obtained from family
      donors at the ten blood banks run by the National Transfusion Blood Service
      (NTBS) under the auspices of the International Red Cross. The remaining 20% are
      collected in hospital laboratories not affiliated with the NTBS but where blood
      bank procedures are used including the ability to screen for HIV contamination.
      Transfusion is thus a safe procedure in the major towns of Ethiopia. Screening
      for hepatitis B is performed only on blood to be administered to children and
      foreigners.

PMID- 10088112
TI  - [Frequency and causes of maternal mortality in a hospital environment in
      Ouagadougou, Burkina Faso].

PMID- 10088113
TI  - [Frequency of malaria in adult expatriates consulting for a fever in 4 medical
      social centers in Africa].

PMID- 10088114
TI  - [Antibiotic resistance of strains of Neisseria gonorrhoeae isolated in Dijibouti
      from 1995 to 1997].

PMID- 10088115
TI  - [Identification of a focus of bejel in Mauritania].

PMID- 10088116
TI  - Hope, not hype, for the future of stem-cell-based therapies.

PMID- 10088117
TI  - DNA vaccine shows promise for malaria.

PMID- 10088118
TI  - Tackling the molecular basis of preterm birth.

PMID- 10088119
TI  - A breath of fresh air for patients with lung disease?

PMID- 10088120
TI  - Is Tourette's syndrome one of the PANDAS?

PMID- 10088121
TI  - Nuclear inclusions in CAG repeat diseases: toxic or protective?

PMID- 10088122
TI  - Charting the genome.

PMID- 10088123
TI  - Vitamin E: blocking the beginnings of atherosclerosis?

PMID- 10088124
TI  - Sperm conceive cues in surprising ways.

PMID- 10088125
TI  - Papilloma virus: tools and vectors.

PMID- 10088126
TI  - Parasite genomes: drugs and vaccines up for grabs.

PMID- 10088127
TI  - Why are dendritic cells central to cancer immunotherapy?
AB  - Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable
      alternative to radiation or chemotherapy in the treatment of cancer. The
      resurgence of interest in cancer immunotherapy reflects the promising results
      that have been obtained in both animal models and early clinical trials with the
      DC-based approach. Here I suggest that this optimism is justified because the
      efficient capture and presentation of antigens by DCs is central to the induction
      of an immune response. I argue that the mechanism by which DCs capture antigen
      suggests that the immune system might actually be 'blind' to tumours, thereby
      challenging the theory of immune surveillance.

PMID- 10088128
TI  - Expanded-capacity adenoviral vectors--the helper-dependent vectors.
AB  - Significant advances have recently been made in the development of vectors and
      gene-delivery systems for gene therapy. Experiments performed over the past
      decade have revealed how vectors will have to be modified to make them a
      clinically viable treatment option. In the case of adenovirus (Ad) vectors, which
      have been particularly useful as gene delivery vehicles, the main drawback
      associated with their use is vector-mediated immunogenicity. Recent modifications
      of the Ad backbone have led to the development of helper-dependent (HD) Ad
      vectors, which are completely devoid of all viral protein-coding sequences. These
      modifications have significantly reduced the immunogenicity of Ad vectors and
      have enhanced their safety. It is expected that HD vectors will become important
      tools for future clinical gene therapy.

PMID- 10088129
TI  - Chimeric viral vectors--the best of both worlds?
AB  - Gene therapy to correct defective genes requires efficient gene delivery and long
      term gene expression. The vector systems currently available have not allowed the
      simultaneous provision of both of these goals. Several groups are now developing
      chimeric viral vector systems that incorporate the favorable attributes of two
      different viral vectors. These chimeric vectors might allow the goals for
      specific gene therapy applications to be realized.

PMID- 10088130
TI  - Virulence factors of Helicobacter pylori: implications for vaccine development.
AB  - Helicobacter pylori is one of the most common infectious diseases in humans and
      causes gastritis, peptic ulcer disease and malignant tumours of the stomach. This
      review discusses how H. pylori can colonize the human stomach, an ecological
      niche that is protected against all other bacteria. Knowledge about the virulence
      factors of H. pylori has accumulated rapidly over the last decade. Together with
      the information contained in the complete H. pylori genome sequence, this
      knowledge is now being applied in the search for a vaccine against this global
      pathogen.

PMID- 10088131
TI  - Blood flow and vascular gene expression: fluid shear stress as a modulator of
      endothelial phenotype.
AB  - Vascular endothelium, the cellular monolayer lining the entire cardiovascular
      system, is exposed to a variety of biochemical and biomechanical stimuli. Fluid
      shear stresses generated by blood flow in the vasculature can profoundly
      influence the phenotype of the endothelium by regulating the activity of certain
      flow-sensitive proteins (for example, enzymes), as well as by modulating gene
      expression. The finding that specific fluid mechanical forces can alter
      endothelial structure and function has provided a framework for a mechanistic
      understanding of flow-dependent processes, ranging from vascular remodeling in
      response to hemodynamic changes, to the initiation and localization of chronic
      vascular diseases such as atherosclerosis.

PMID- 10088132
TI  - M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic,
      blocks dizocilpine-induced prepulse inhibition deficits in Sprague-Dawley and
      Wistar rats.
AB  - In a recent study using Wistar rats, the serotonergic 5-HT2 receptor antagonists
      ketanserin and risperidone reduced the disruptive effects of the noncompetitive N
      methyl-D-aspartate (NMDA) antagonist dizocilpine on prepulse inhibition (PPI),
      suggesting that there is an interaction between serotonin and glutamate in the
      modulation of PPI. In contrast, studies using the noncompetitive NMDA antagonist
      phencyclidine (PCP) in Sprague-Dawley rats found no effect with 5-HT2
      antagonists. To test the hypothesis that strain differences might explain the
      discrepancy in these findings, risperidone was tested for its ability to reduce
      the PPI-disruptive effects of dizocilpine in Wistar and Sprague-Dawley rats.
      Furthermore, to determine which serotonergic receptor subtype may mediate this
      effect, the 5-HT2A receptor antagonist M100907 (formerly MDL 100,907) and the 5
      HT2C receptor antagonist SDZ SER 082 were tested against dizocilpine. Recent
      studies have found that the PPI-disruptive effects of PCP are reduced by the
      alpha 1 adrenergic receptor antagonist prazosin. Furthermore, the alpha 1
      receptor agonist cirazoline disrupts PPI. As risperidone and M100907 have
      affinity at the alpha 1 receptor, a final study examined whether M100907 would
      block the effects of cirazoline on PPI. Risperidone partially, but
      nonsignificantly, reduced the effects of dizocilpine in Wistar rats, although
      this effect was smaller than previously reported. Consistent with previous
      studies, risperidone did not alter the effects of dizocilpine in Sprague-Dawley
      rats. Most importantly, M100907 pretreatment fully blocked the effect of
      dizocilpine in both strains; whereas SDZ SER 082 had no effect. M100907 had no
      influence on PPI by itself and did not reduce the effects of cirazoline on PPI.
      These studies confirm the suggestion that serotonin and glutamate interact in
      modulating PPI and indicate that the 5-HT2A receptor subtype mediates this
      interaction. Furthermore, this interaction occurs in at least two rat strains.

PMID- 10088133
TI  - Dissociable deficits in the decision-making cognition of chronic amphetamine
      abusers, opiate abusers, patients with focal damage to prefrontal cortex, and
      tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.
AB  - We used a novel computerized decision-making task to compare the decision-making
      behavior of chronic amphetamine abusers, chronic opiate abusers, and patients
      with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC.
      We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT)
      activity using a tryptophan-depleting amino acid drink in normal volunteers.
      Chronic amphetamine abusers showed suboptimal decisions (correlated with years of
      abuse), and deliberated for significantly longer before making their choices. The
      opiate abusers exhibited only the second of these behavioral changes.
      Importantly, both sub-optimal choices and increased deliberation times were
      evident in the patients with damage to orbitofrontal PFC but not other sectors of
      PFC. Qualitatively, the performance of the subjects with lowered plasma
      tryptophan was similar to that associated with amphetamine abuse, consistent with
      recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine
      abusers. Overall, these data suggest that chronic amphetamine abusers show
      similar decision-making deficits to those seen after focal damage to
      orbitofrontal PFC. These deficits may reflect altered neuromodulation of the
      orbitofrontal PFC and interconnected limbic-striatal systems by both the
      ascending 5-HT and mesocortical dopamine (DA) projections.

PMID- 10088134
TI  - Effects of atypical antipsychotic drug treatment on amphetamine-induced striatal
      dopamine release in patients with psychotic disorders.
AB  - Clozapine, risperidone, and other new "atypical" antipsychotic agents are
      distinguished from traditional neuroleptic drugs by having clinical efficacy with
      either no or low levels of extrapyramidal symptoms (EPS). Preclinical models have
      focused on striatal dopamine systems to account for their atypical profile. In
      this study, we examined the effects of clozapine and risperidone on amphetamine
      induced striatal dopamine release in patients with psychotic disorders. A novel
      11C-raclopride/PET paradigm was used to derive estimates of amphetamine-induced
      changes in striatal synaptic dopamine concentrations and patients were scanned
      while antipsychotic drug-free and during chronic treatment with either clozapine
      or risperidone. We found that amphetamine produced significant reductions in
      striatal 11C-raclopride binding during the drug-free and antipsychotic drug
      treatment phases of the study which reflects enhanced dopamine release in both
      conditions. There were no significant differences in % 11C-raclopride changes
      between the two conditions indicating that these atypical agents do not effect
      amphetamine-related striatal dopamine release. The implications for these data
      for antipsychotic drug action are discussed.

PMID- 10088135
TI  - The vigilance promoting drug modafinil increases extracellular glutamate levels
      in the medial preoptic area and the posterior hypothalamus of the conscious rat:
      prevention by local GABAA receptor blockade.
AB  - The effects of modafinil on glutamatergic and GABAergic transmission in the rat
      medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed.
      Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA
      and PH. Local perfusion with the GABAA agonist muscimol (10 microM), reduced,
      while the GABAA antagonist bicuculline (1 microM and 10 microM) increased
      glutamate levels. The modafinil (100 mg/kg)-induced increase of glutamate levels
      was antagonized by local perfusion with bicuculline (1 microM). When glutamate
      levels were increased by the local perfusion with the glutamate uptake inhibitor
      L-trans-PDC (0.5 mM), modafinil produced an additional enhancement of glutamate
      levels. Modafinil (1-33 microM) failed to affect [3H]glutamate uptake in
      hypothalamic synaptosomes and slices. These findings show that modafinil
      increases glutamate and decreases GABA levels in MPA and PH. The evidence that
      bicuculline counteracts the modafinil-induced increase of glutamate levels
      strengthens the evidence for an inhibitory GABA/glutamate interaction in the
      above regions controlling the sleep-wakefulness cycle.

PMID- 10088136
TI  - THA improves word priming and clonidine enhances fluency and working memory in
      Alzheimer's disease.
AB  - We investigated the effects of a single administration of a cholinesterase
      inhibitor, tetrahydroaminoacridine (THA, 25 and 50 mg, orally), and an alpha 2
      agonist, clonidine (0.5 and 2 micrograms/kg, orally), on neuropsychologic
      performance in two groups of patients with Alzheimer's disease (AD). Clonidine
      enhanced a spatial working memory and verbal fluency, but had no effect on
      spatial span or word priming. THA enhanced word priming, but had no effect on
      other performance measures. Our data suggests that degeneration of the LC
      noradrenergic system and the cholinergic cells of the basal forebrain have
      different functional consequences during the progression of AD. Finally, a
      combined treatment with noradrenergic and cholinergic drugs might produce a
      qualitatively broader effect on cognitive functions than either of the treatments
      alone, and more effectively attenuate clinical dementia.

PMID- 10088137
TI  - Differential effects of mental stress on plasma homovanillic acid in
      schizophrenia and normal controls.
AB  - We previously reported that mental stress by Kraepelin's arithmetic test
      decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal
      healthy human subjects. The present study was undertaken to determine whether
      this pattern of changes in pHVA concentrations resulting from mental stress is
      altered in patients with schizophrenia. Fourteen male patients with schizophrenia
      including those under ongoing neuroleptic treatment and 14 normal male volunteers
      participated in the study. Following overnight fast and restricted physical
      activity, the subjects performed Kraepelin's arithmetic test for 30 minutes.
      Plasma samples were collected immediately before and after the test for
      measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect
      was observed due to a decrease in pHVA levels by the Kraepelin test in control
      subjects but not in patients with schizophrenia. Changes in pHVA levels during
      the Kraepelin test positively correlated with pre-test pHVA levels in control
      subjects, while this correlation was not observed in patients with schizophrenia.
      These results may be further support for the presence of a dopamine-dependent
      restitutive system in the brain. The absence of response of pHVA levels to mental
      stress in patients with schizophrenia may indicate that the dopamine restitutive
      system in these patients is disrupted or already down-regulated, as previously
      predicted.

PMID- 10088138
TI  - Negative immunoregulatory effects of antidepressants: inhibition of interferon
      gamma and stimulation of interleukin-10 secretion.
AB  - There is now some evidence that major depression is accompanied by activation of
      the inflammatory response system. There is also some evidence that
      antidepressants may suppress the release of cytokines, such as interleukin-1 beta
      (IL-1 beta) and IL-6 by activated monocytes and IL-2 and interferon-gamma (IFN
      gamma) by activated T cells. This study was carried out to examine the effects of
      clomipramine, sertraline, and trazodone on the stimulated production of IFN
      gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory
      cytokine. Whole blood of nine healthy volunteers was stimulated with PHA, 5
      micrograms/mL and LPS, 25 micrograms/mL for 72 hr with and without incubation
      with clomipramine, 10(-6) and 10(-9) M, sertraline, 10(-6) and 10(-8) M, and
      trazodone, 10(-6) and 10(-8) M. All three antidepressants significantly reduced
      IFN gamma secretion, whereas clomipramine and sertraline significantly increased
      IL-10 secretion in culture supernatant. All three antidepressants significantly
      reduced the IFN gamma/IL-10 ratio. The results suggest that antidepressants, at
      concentrations in the therapeutical range, have negative immunoregulatory effects
      through inhibition of IFN gamma and stimulation of IL-10 release.

PMID- 10088139
TI  - Sustained antidepressant effect of sleep deprivation combined with pindolol in
      bipolar depression. A placebo-controlled trial.
AB  - Total sleep deprivation (TSD) shows powerful but transient clinical effects in
      patients affected by bipolar depression. Pindolol blocks the serotonergic 5-HT1A
      autoreceptor, thus improving the antidepressant effect of selective serotonin
      reuptake inhibitors. We evaluated the interaction of TSD and pindolol in the
      treatment of acute episodes of bipolar depression. Forty bipolar depressed
      inpatients were randomized to receive pindolol 7.5 mg/day or placebo for nine
      days in combination with three consecutive TSD cycles. Pindolol significantly
      improved the antidepressant effect of TSD, and prevented the short-term relapse
      after treatment. The response rate (HDRS scores < 8) at the end of treatment was
      15/20 for pindolol, and 3/20 for placebo. Coadministration of pindolol and TSD
      resulted in a complete response, which could be sustained for six months with
      lithium salts alone, in 65% of cases. This results suggest a major role for
      serotonergic transmission in the mechanism of action of TSD, and makes TSD
      treatment more effective in the treatment of bipolar depression.

PMID- 10088140
TI  - Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in
      panic disorder.
AB  - The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations
      within brain stress systems that secondarily influence the immune system have
      been documented. A recent report indicated elevations of serotonin (5-HT) and
      ganglioside antibodies in patients with primary fibromyalgia, a condition with
      documented associations with panic disorder. In line with our interest in
      dysregulated 5-HT systems in panic disorder (PD), we wished to assess if
      antibodies directed at the 5-HT system were elevated in patients with PD in
      comparison to healthy volunteers. Sixty-three patients with panic disorder and 26
      healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti
      5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors).
      To include all subjects in one experiment, three different batches were run
      during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a
      significant group effect [patients > controls (p = .007)] and batch effect but no
      interaction. The mean effect size for the three batches was .76. Following Z
      score transformation of each separate batch and then combining all scores,
      patients demonstrated significantly elevated levels of plasma serotonin anti
      idiotypic antibodies. Neither sex nor age as covariates affected the significance
      of the results. There was a strong correlation between anti-serotonin antibody
      and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies:
      there was a significant diagnosis effect [patients > controls (p = .037)]. Mean
      effect size for the three batches was .52. Upon Z-score transformation, there was
      a diagnosis effect with antibody elevations in patients. Covaried for sex and
      age, the result falls below significance to trend levels. The data raise the
      possibility that psychoimmune dysfunction, specifically related to the 5-HT
      system, may be present in PD. Potential interruption of 5-HT neurotransmission
      through autoimmune mechanisms may be of pathophysiologic significance in certain
      patients with panic disorder. It remains to be demonstrated if the peripheral
      autoimmunity is representative of CNS 5-HT neuronal alterations. Replication
      appears warranted.

PMID- 10088141
TI  - Schizophrenia, monoamine oxidase activity, and cigarette smoking.
AB  - Reduced monoamine oxidase activity has been proposed as a marker for
      vulnerability to schizophrenia. Reduced monamine oxidase activity has also been
      shown to occur in cigarette smokers. This study compared monamine oxidase
      activity level in a matched group of patients with schizophrenia who smoked with
      a group who did not. Lower levels of monoamine oxidase activity were found in the
      smokers and this is the likely explanation for the low levels hypothesized as a
      marker for schizophrenia.

PMID- 10088142
TI  - Cocaine withdrawal and the cerebral influx of [18F]fluoro-L-DOPA (FDOPA)

PMID- 10088143
TI  - The spatial organization of the cortical projection system of the nucleus
      accumbens of the dog brain.

PMID- 10088144
TI  - Chronic remitting experimental allergic encephalomyelitis in Lewis rats as a
      model of multiple sclerosis.

PMID- 10088145
TI  - Changes in the physiological roles of neurotransmitters during individual
      development.
AB  - The classical neurotransmitters (acetylcholine and biogenic monoamines) are
      multifunctional substances involved in intra- and intercellular signaling at all
      stages of ontogenesis in multicellular animals. A cyclical scheme is proposed to
      describe age-related changes in neurotransmitter functions at different stages of
      development from oocyte maturation to neuron formation. This may reflect not only
      the temporospatial organization of neurotransmitter processes, but also the
      origin of the functions of acetylcholine and biogenic monoamines from the
      protosynapses of the cleaved embryo to neuronal synapses.

PMID- 10088146
TI  - Specific characteristics of cholinergic mechanisms of short-term memory in
      monkeys for different types of visual information: the effects of amizil.
AB  - Experiments on rhesus macaques were used to study the relationship between the
      characteristics of delayed visual differentiation and stimulus properties in
      conditions of pharmacological treatment with the m-cholinoreceptor blocker
      amizil, with the aim of identifying how modification of cholinergic structures
      affects different types of information. Disturbances to short-term memory for all
      stimuli consisted of reductions in the duration of retention and increases in
      motor reaction times, but occurred at different doses of the blocker: amizil at a
      dose of 0.3 mg/kg significantly decreased the retention duration for information
      relating to spatial relationships. Delayed discrimination of shape, contrast, and
      size worsened after treatment with amizil at a dose of 0.45-0.50 mg/kg, while
      decreases in the duration of short-term storage of information relating to color
      started after amizil doses of 0.6-0.8 mg/kg. It is suggested that the short-term
      memory system includes a set of neurophysiological mechanisms in which the
      cholinergic structures are organized differently and whose specific properties
      result in differences in the characteristics of short-term storage of different
      types of visual information.

PMID- 10088147
TI  - Recovery of memory in chicks after disruption during learning: the reversibility
      of amnesia induced by protein synthesis inhibitors.
AB  - Protein synthesis inhibitors given during learning are known to disrupt memory in
      various animal species in several models of learning. However, there are
      suggestions that amnesia induced by protein synthesis inhibitors is not permanent
      -memory can be recovered by a reminder procedure, i.e., by presenting the animal
      with one of the components of the external environment which was part of the
      learning situation. The aim of the present work was to determine the existence of
      the reminder phenomenon in a well-studied model of single-session training to
      passive avoidance in chicks. Cycloheximide and anisomycin were used to induce
      amnesia. Reminder was performed using the aversive taste of methylanthranilate 24
      h after training, and testing was conducted 48 h after training. The results
      obtained provide evidence that memory disrupted by protein synthesis inhibitors
      in chicks can be recovered by the reminder procedure.

PMID- 10088148
TI  - Systems analysis of the neuroimmunological mechanisms of memory.
AB  - Experimental data on the role of immunomodulators in the mechanisms of
      neurological memory are presented and assessed from the point of view of
      functional systems theory. It is demonstrated that the immunomodulator
      interleukin-1 beta and the alpha-2-interferon fragment RITLY improve the
      processes of learning and reproduction of an active defensive habit. These
      substances were found to have effects on the productivity of behavior, on
      orientational-investigative reactions, and on vocalization in response to a
      conditioned signal. A positive correlation between intersignal activity and
      productivity is demonstrated as a reflection of the mechanisms of anticipatory
      reorganization of behavior during learning. However, interleukin has a selective
      action depending on the ethological conditions obtained during learning.

PMID- 10088149
TI  - Restoration of emotional stress reactions in rats following disruption of the
      limbic structures of the brain by delta-sleep-inducing peptide.
AB  - This report describes studies of delta-sleep-inducing peptide in the mechanism of
      compensating emotional behavior following disruption of a number of structures of
      the limbic complex (the septum and amygdala). Studies were performed in male
      Wistar rats. Peptide was given i.p. at a dose of 60 nmol/kg. The
      individual/typological characteristics of the rats' behavior and their resistance
      to stress was predicted using an open field test. Emotional stress was modeled by
      immobilizing the animals and applying electric shocks to the skin. Stress was
      assessed in terms of survival, adrenal hypertrophy, and thymic involution in
      stress conditions. Bilateral lesioning to brain structures was carried out by
      anodic polarization. The results obtained showed that the septum and amygdala
      play a significant role in the mechanisms of resistance to emotional stress.
      Bilateral disruption of these structures significantly decreased the animals'
      resistance to emotional stress, producing alterations in behavior in the open
      field test, increasing the lethality of acute emotional stress, and inducing
      changes in stress marker organs (the adrenals and thymus) in stress conditions,
      as compared to controls. Administration of peptide to animals with lesions to the
      septum or amygdala increased their resistance to emotional stress, as indicated
      by open field test behavior, survival, and adrenal and thymus weight in stress
      conditions. Thus, doses of delta-sleep-inducing peptide partially reverse
      reductions in stress resistance in animals with lesions to structures of the
      limbic complex.

PMID- 10088150
TI  - Correlates of sequential elements of bimanual behavior in the neuronal activity
      of the neostriatum in monkeys.
AB  - Neuron spike activity was recorded in the putamen of monkeys trained to perform
      bimanual operant behavior consisting of nine separate steps. Neuronal reactions
      were present at all steps: in 52-62% of cases during movement, and in 27-36% of
      cases during responses to the trigger and conditioned signals and as the monkeys
      decided which was the working hand. The proportion of inhibitory responses to the
      trigger stimulus was 9%, while inhibitory reactions accounted for 68% of
      reactions during hand movement in response to the conditioned signal, 33% of
      reactions when this same hand was used to collect food reinforcement, and 33% of
      reactions during simultaneous movement of both hands. Reactions significantly
      differentiating between right- and left-sided tasks were seen at all stages of
      working-hand decision-taking and in reactions to the signal indicating the
      correctness of the selection, but were not seen for reactions to the conditioned
      signal or for activity accompanying movements of one of the animal's hands. These
      data provide evidence indicating that each step of the complex operant behavior,
      individual systems of putamen neuronal reactions were created with qualitatively
      different integral sensitivity to instantaneous behavior.

PMID- 10088151
TI  - Responses of hypothalamic neurons to stimulation of the vestibular nerve and
      lateral vestibular nucleus in the rabbit.
AB  - Acute experiments were performed on rabbits to study the responses of neurons in
      the anterior, ventromedial, and posterior nuclei of the hypothalamus to single,
      paired, and rhythmic stimulation of the vestibular nerve and lateral vestibular
      nucleus of Deiters. The data obtained showed that neurons of the posterior
      nucleus of the hypothalamus were the most sensitive. Three types of response were
      seen from hypothalamic neurons, with short, long, and intermediate latent
      periods. This provides evidence that ascending afferent spike activity from the
      lateral vestibular nucleus of Deiters to the hypothalamus is mediated by mono-,
      oligo-, and polysynaptic pathways.

PMID- 10088152
TI  - Calcium currents and GABAB receptors in the dorsal sensory cells of the lamprey
      spinal cord.
AB  - Patch-clamp studies were performed on the isolated dorsal sensory cells of the
      spinal cords of three species of lamprey, Ichthyomyzon unicuspis, Petromyzon
      marinus, and Lampetra fluviatilis, to measure changes in the amplitudes of
      calcium current induced by GABA and its specific antagonists and agonists. The
      experiments showed that GABA (4 mM) reduced the peak amplitude of the calcium
      current by 28.5 +/- 4.9%, with subsequent recovery to 96.2 +/- 9.2% of control (n
      = 45). The GABAB agonist baclofen had similar effects. The GABAA agonists glycine
      and taurine had no effect on the Ca2+ current. The inhibitory effect of GABA was
      blocked by 2-hydroxysaclofen (a GABAB antagonist), but persisted in the presence
      of bicuculline (a GABAA antagonist). These results are evidence that the
      membranes of dorsal sensory cells contain GABAB receptors, which significantly
      increases our understanding of the mechanisms of presynaptic inhibition in the
      spinal cords of the cyclostomata.

PMID- 10088153
TI  - The effects of baclofen on calcium channel currents in dorsal sensory cells of
      the spinal cord in the lamprey.
AB  - Dorsal sensory cells isolated from the spinal cord of the lamprey species
      Ichthyomyzon unicuspis and Lampetra fluviatilis were used for whole-cell patch
      clamp studies of the effects of baclofen on calcium channel currents, evoked in
      conditions in which Na+, K+ currents were blocked, by depolarizing membranes from
      constant holding potentials of -100 or -80 mV to +30 mV. Ba ions were used as
      carriers of currents through calcium channels. These studies demonstrated that
      baclofen (0.5 mM) decreased the peak amplitude of the Ba2+ current by an average
      of 22.5 +/- 4.2% (n = 12) in dorsal sensory cells of the lamprey Ichthyomyzon
      unicuspis and by 28.4 +/- 3.3% in the dorsal sensory cells of Lampetra
      fluviatilis (n = 25). The conductivity of dorsal sensory cell membranes in the
      presence of baclofen (and GABA) did not change. The blocking action of baclofen
      persisted in the presence of bicuculline (100 microM) and was lifted by addition
      of delta-aminovaleric acid and 2-hydroxysaclofen to the perfusing solution. These
      results are interpreted as evidence for the presence of GABAB receptors in dorsal
      sensory cell membranes. The data were compared with published results, and the
      question of the functional significance of GABAB receptors in the dorsal sensory
      cells (primary afferent cells) of cyclostomata is discussed.

PMID- 10088154
TI  - The selective effects of a monoclonal antibody against neural growth-related
      protein A3G7 on central mechanisms of several types of defensive behavior in
      adult rats.
AB  - Studies were carried out into the effects of monoclonal antibodies to protein
      A3G7, which is associated with the differentiation of cerebellar and hippocampal
      neurons, on the development, retention, and reproduction of a habituated acoustic
      startle response and freezing behavior in rats. Application of monoclonal
      antibody (50 ng) to the vermis of the cerebellum selectively disrupted the
      retention of long-term habituation of the acoustic startle response, while a
      higher dose (5 micrograms) inhibited both retention of long-term habituation of
      the acoustic startle response and conditioned freezing behavior. Monoclonal
      antibody (10 micrograms) disrupted the development and retention of short-term
      and long-term extinction of the acoustic startle response, as well as conditioned
      freezing behavior. These data provide experimental support for the systemogenesis
      hypothesis of behavioral acts and for the concept that there is a single
      molecular basis for development and learning.

PMID- 10088155
TI  - Integrative activity of cortical neurons in the systems organization of food
      behavior.
AB  - The spike activity of neurons in the visual and parietal areas of the cerebral
      cortex was studied in cats at sequential steps of operant food-procuring
      behavior. Cells had individual patterns of spike activity, and changes in
      different areas of the cortex were associated with the modality of the
      conditioned stimulus, the level of food motivation, and the effectiveness of
      achieving the step-by-step results of behavior. The distribution of spike
      activity on the axon of a neuron reflected the dynamics of its integrative
      activity and depended on the pre-existing functional state of the cell and the
      ongoing synaptic activation during the development of key mechanisms of the
      central architecture of the functional system for the behavioral act.

PMID- 10088156
TI  - The dynamics of pain perception in conditions of purposive activity.
AB  - Pain threshold sensitivity determination and recording of somatosensory evoked
      potentials in response to electrical skin stimulation were used to study the
      dynamics of pain sensitivity in medical students in mid-semester before blood
      donor and examination procedures and in the post-procedure period during
      performance of an editing test. Increases in pain sensitivity thresholds were
      seen in all subjects during the examination period and on performance of the
      editing test. Differences in changes in evoked potential amplitudes were found,
      depending on the individual-typological characteristics of the nervous system and
      the quality of motivationally determined states. Subjects with different
      individual-typological characteristics had different subjective pain sensation
      dynamics in test conditions.

PMID- 10088157
TI  - The effects of phototherapy on psychoautonomic neurotic disorders.
AB  - Bright white light therapy (two-week courses of daily morning sessions lasting 1
      h; distance from lamp 60 cm; light intensity 3300 lux) was used in 51 patients
      with neurotic autonomic dystonia syndrome. Improvements were obtained in 59% of
      patients (group 1), while treatment was not effective in 41% (group 2). Changes
      in virtually all neuroendocrine, motivational, psychoautonomic, pain, and
      psychopathological symptomatology were obtained. At the end of treatment,
      patients in group 1 had increases in the EEG power spectrum, increases in slow
      activity and reductions in rapid activity on both sides; coefficients of
      asymmetry approached those in controls, and there were increases in urinary
      excretion of catecholamine and serotonin metabolites. In group 2, initially
      increased EEG power spectra increased further, because of increases in theta and
      beta rhythms bilaterally, and the coefficient of asymmetry decreased sharply;
      total excretory activity decreased. Symptoms and psychophysiological measures
      positively and negatively affected by phototherapy were identified.

PMID- 10088158
TI  - Amiodarone and thyroid disease.

PMID- 10088159
TI  - 99Tcm-sestamibi imaging of inhibition of the multidrug resistance transporter in
      a mouse xenograft model of human breast cancer.
AB  - Sestamibi is known to be a substrate for P-glycoprotein, the membrane transporter
      which confers multidrug resistance by pumping certain chemotherapeutic agents out
      of tumour cells. In this study, the utility of sestamibi imaging for detecting
      inhibition of P-glycoprotein (Pgp) function by two potent, second-generation
      chemosensitizers, PSC833 and GG918, was assessed in a mouse xenograft model of
      multidrug-resistant human breast cancer, MCF7-AdrR. Preliminary in vitro studies
      confirmed that MCF7-AdrR cells accumulate only low levels of sestamibi and that
      both sensitizers inhibit transporter function to a similar extent, resulting in
      20-fold higher accumulation of sestamibi. MCF7-AdrR cells were grown as a
      xenograft in SCID mice and sestamibi kinetics in the tumour were analysed by
      dynamic imaging (30 frames at a rate of one frame per minute). Administration of
      either chemosensitizer produced a dose-dependent slowing of the efflux rate of
      sestamibi compared to untreated tumours. The same effect was evident in two
      additional parameters: percent activity remaining at 30 min determined by imaging
      and sestamibi levels measured in excised tissues. These results show that
      sestamibi imaging can detect inhibition of Pgp function and suggest that this
      approach could be used clinically to document effective delivery of
      chemosensitizers.

PMID- 10088160
TI  - Radioimmunoguided surgery of colorectal carcinoma with an 111In-labelled anti
      TAG72 monoclonal antibody.
AB  - Radioimmunoscintigraphy (RIS) and radioimmunoguided surgery (RIGS) were assessed
      for their usefulness in patients with colorectal carcinoma. Twenty-nine patients
      (18 primary tumours, 10 with a suspicion of recurrence and one colonic
      diverticulitis) were studied. Radioimmunoscintigraphy was performed 48 and 72 h
      after the injection of an anti-TAG72 monoclonal antibody (CYT-103) labelled with
      111In. Radioimmunoguided surgery was performed between 72 and 96 h post
      injection. During surgery, a systematic screening was performed with a hand-held
      gamma detecting probe and a surgical index (tumour-to-normal tissue) was
      obtained. There were statistically significant differences between counts in
      normal tissue versus tumour (P < 0.001) and RIGS was considered positive for the
      detection of tumour if the ratio between the counts in the area suspicious of
      tumour and the counts in the normal tissue was greater than 1.5. The overall
      sensitivity for RIS and RIGS was 71.4% (55.6% in primary tumours and 100% in
      recurrences) and 82.1% (83.3% in primary tumours and 80% in recurrences),
      respectively. Radioimmunoguided surgery changed the surgical procedure in two
      cases with small tumour deposits. Occult regional lymph node involvement in
      primary tumours was not found; therefore, RIGS, as a complementary technique to
      RIS, is particularly useful in recurrences and can help the surgeon in the
      resection of small tumour deposits which are difficult to localize.

PMID- 10088161
TI  - 11C-acetate clearance in nasopharyngeal carcinoma.
AB  - This study assessed 11C-acetate turnover (clearance) in nasopharyngeal carcinoma
      (NPC). Data were acquired by dynamic PET after the intravenous injection of 4.625
      MBq.kg-1 body weight of 11C-acetate for 30 min. Tomograms were reconstructed and
      evaluated visually. A time-activity curve of the nasopharynx and neck was
      generated and the clearance rate of 11C-acetate from the nasopharynx in the slow
      phase and from NPC was calculated using 0.693/T1/2. Ten patients with
      nasopharyngeal carcinoma and nine normal subjects were studied. The clearance of
      11C-acetate from the normal nasopharynx was rapid and biexponential, in contrast
      to the rapid uptake followed by extremely slow clearance in patients with NPC.
      The clearance rate (mean +/- S.D.) was 0.0074 +/- 0.0042 in NPC and 0.0263 +/-
      0.0152 in controls in the slow phase, being significantly different between the
      two groups with no overlap. All nasopharyngeal carcinomas were clearly
      visualized, in contrast to no obvious retention in the normal nasopharynx. Our
      initial results indicate that 11C-acetate clearance can be used to differentiate
      nasopharyngeal carcinoma from a normal nasopharynx. This finding may lead to new
      applications of 11C-acetate in oncology.

PMID- 10088162
TI  - Bone marrow immunoscintigraphy for the detection of skeletal metastases in
      patients with breast cancer.
AB  - In this study, we evaluated the efficacy of bone marrow immunoscintigraphy (BMIS)
      for the detection of skeletal metastases in 23 patients with histologically
      confirmed breast cancer. All patients underwent whole-body BMIS 3-6 h after the
      intravenous injection of 0.20-0.33 mg of the intact anti-NCA 95 MAb BW 250/183
      labelled with 259-555 MBq 99Tcm and a whole-body 99Tcm-MDP bone scan. In four
      patients, BMIS SPET of the lumbar spine was also performed. Serum alkaline
      phosphatase was determined in all patients and the level of human anti-mouse
      antibody (HAMA) in 16. Final diagnosis was confirmed by radiology and 2 years
      follow-up. Compared with the 99Tcm-MDP bone scan, BMIS demonstrated better
      specificity (88% vs 75%) and a better positive predictive value (92% vs 85%).
      There were no significant differences between BMIS and the bone scan in the
      detection of skeletal metastases (P > 0.05). In one patient with normal planar
      BMIS of the lumbar spine, SPET disclosed a metastatic lesion in the bone marrow.
      The correlation coefficient between BMIS and bone scan and between BMIS and serum
      alkaline phosphatase was r = 0.688 and r = 0.483 respectively. One patient
      developed a minor HAMA response after BMIS. Patients with diffuse increased
      activity of the skull on the bone scan had a significantly higher skull to whole
      body ratio on BMIS (P < 0.01). Thus BMIS can improve the specificity and positive
      predictive value of bone scanning in the detection of skeletal metastases, with a
      low HAMA response. Diffuse increased activity of the skull on bone scans could be
      explained by bone marrow extension. SPET scanning of the spine may improve the
      sensitivity of BMIS.

PMID- 10088163
TI  - 111In-labelled bleomycin complex for the differentiation of high- and low-grade
      gliomas.
AB  - The aim of this study was to evaluate 111In-labelled bleomycin complex (111In
      BLMC) SPET in the differentiation of high- and low-grade gliomas. Nineteen glioma
      patients, 14 with high-grade and five with low-grade tumours, were studied 1, 4
      and 24 h after the injection of 111In-BLMC. In the high-grade glioma group, there
      was significant uptake of 111In-BLMC in 12 patients and no uptake in two patients
      based on the visual classification of SPET images at 4 and 24 h. In the low-grade
      glioma group, one patient had low uptake at 4 and 24 h, but the other four
      patients showed no visible uptake. The mean tumour to extracerebral circulation
      activity ratio (T/Cr) at 4 h was 0.13 +/- 0.10 (n = 5) in low-grade gliomas and
      1.7 +/- 1.0 (n = 14) in high-grade gliomas. At 24 h the T/Cr ratios were 0.56 +/-
      0.21 and 3.4 +/- 1.7, respectively. The mean tumour to contralateral normal brain
      activity ratios (T/Br) were 5.0 +/- 3.9 (4 h) and 3.0 +/- 2.8 (24 h) in low-grade
      gliomas, and 37.2 +/- 37.3 (4 h) and 8.3 +/- 8.2 (24 h) in high-grade gliomas.
      These higher T/Br ratios did not, however, result in improved differentiation
      between the two groups of gliomas; at 4 h the T/Cr and T/Br ratios were of equal
      value, as two high-grade gliomas would have been misclassified as low-grade, but
      at 24 h the T/Br ratio resulted in more misclassifications. Our results show that
      111In-BLMC can be used in the differentiation of high- and low-grade gliomas and
      that the selection of the reference area for calculating tumour to non-tumour
      ratios is important.

PMID- 10088164
TI  - Brain uptake of iodinated L-meta-tyrosine, a metabolically stable amino acid
      derivative.
AB  - The possibility of using L-meta-tyrosine (L-mTyr) with high metabolic stability
      and amino acid transport affinity was evaluated. mTyr was first separated into D-
      and L-isomers with high-performance liquid chromatography and both were labelled
      with non-carrier-mediated 125I. Biodistribution and pharmacological studies of
      radioiodinated mTyr in mice and rats were then performed. 125I-L-mTyr showed
      greater accumulation in the brain and the pancreas. It accumulated in the brain
      stereospecifically in the in vivo studies and by the L-tyrosine competitive
      energy dependent transport system in the in vitro studies. It was resistant to
      deiodination, appeared to have no retention mechanism and was rapidly excreted.
      123I-L-mTyr has the potential of an amino acid transport marker, especially in
      the brain and the pancreas.

PMID- 10088165
TI  - Effects of scatter and attenuation correction on quantitative analysis of beta
      CIT brain SPET.
AB  - The aim of this study was to evaluate the effects of scatter correction (SC) and
      attenuation correction (AC) on the quantification of dopamine transporters using
      123I-beta-CIT brain SPET images. Quantitative analysis was carried out using
      static SPET images obtained 23 h after injection. We calculated V3" [(striatal
      occipital)/occipital ratio] values from images without correction, with AC, and
      with SC and AC. Two types of regions of interest (ROI) were placed on the
      striatum: a small square ROI and a larger ROI containing most of the striatum.
      After validating the correction method in a phantom experiment, a human study was
      carried out involving eight normal volunteers and 15 patients. The larger ROI
      yielded smaller V3" values. The effect of attenuation correction was modest,
      whereas that of scatter correction was marked. It was shown that beta-CIT SPET
      quantification was affected by the size of the ROI, photon scattering and
      attenuation, and that scatter and attenuation correction improved the accuracy of
      the quantification. Methodological standardization in image processing and the
      type of ROI should be considered when a multi-centre trial is planned.

PMID- 10088166
TI  - Cerebral blood flow in patients with normal pressure hydrocephalus.
AB  - Mean cerebral blood flow (CBF) of the whole brain was measured in 48 patients who
      underwent cerebrospinal fluid shunt surgery for normal pressure hydrocephalus
      (NPH) by performing first-pass radionuclide angiography using 99Tcm
      hexamethylpropylene amine oxime. Patients were divided according to outcome into
      an 'excellent' improvement group, a 'good' improvement group, a 'fair'
      improvement group and a 'poor' improvement group. Patients with excellent and
      good improvement had a preoperative mean CBF of 40.4 +/- 3.9 ml.100 g-1.min-1 and
      37.1 +/- 5.5 ml.100 g-1.min-1, respectively, both of which were significantly (P
      < 0.005) higher than that in 11 patients who showed fair improvement (30.8 +/-
      3.2 ml.100 g-1.min-1) and six patients who showed poor improvement (31.8 +/- 2.5
      ml.100 g-1.min-1). Patients with a clinical improvement after shunting had an
      increased postoperative mean CBF. We conclude that patients with a preoperative
      mean CBF of over 35 ml.100 g-1.min-1 can show favourable improvement after a
      shunting procedure, and that the preoperative mean CBF of 32 ml.100 g-1.min-1 can
      be considered the critical level for treatment.

PMID- 10088167
TI  - Comparison of the clearance of radiolabelled nose drops and nasal spray as
      mucosally delivered vaccine.
AB  - The distribution and nasal clearance of 99Tcm-labelled albumin (18.5 MBq), used
      as a mucosal vaccine surrogate for FluMist, was determined in three volunteers.
      The subjects were randomized in a cross-over clinical study design to receive
      either large-particle aerosal (nasal spray) followed by nose drops, or nose drops
      followed by the nasal spray, 1 week apart. Gamma scintigraphy was used to measure
      the distribution and clearance. The 'vaccine' delivered as drops was cleared from
      the nose into the oesophagus and upper stomach at very variable rates. In
      contrast, the nasal spray was uniformly distributed and cleared from the
      nasopharynx with a 50% mean clearance time of 50 min (range 40-60 min) and was
      not detected in the lungs.

PMID- 10088168
TI  - Scintigraphy of de Quervain's tenosynovitis.
AB  - The scintigraphic pattern of de Quervain's tenosynovitis has not previously been
      described. Similar three-phase bone scintigraphy patterns were found in four
      patients with this condition. The characteristic abnormalities consisted of an
      elongated area of increased uptake in the blood flow and blood pool phases in the
      anatomical course of the first dorsal compartment of the wrist, together with
      increased focal uptake of 99Tcm-MDP in the radial styloid on the delayed images.
      This pattern should be recognized and included in the differential diagnosis of
      increased uptake of 99Tcm-MDP in the radial compartment of the wrist.

PMID- 10088169
TI  - Dose rate measurements from radiopharmaceuticals: implications for nuclear
      medicine staff and for children with radioactive parents.
AB  - Following the introduction of a number of radiopharmaceuticals, we assessed the
      dose received by staff working in the nuclear medicine department and also by
      children who may be in close contact with a radioactive parent. We measured
      departure dose rates (microSv.h-1) at distances of 0.1, 0.5 and 1.0 m from the
      skin surface at the level of the thyroid, chest and bladder of patients
      undergoing the following nuclear medicine procedures: MUGA scans using 99Tcm
      labelled red blood cells, myocardial perfusion scans using 99Tcm-labelled
      radiopharmaceuticals, lymphoscintigraphy using colloidal 99Tcm (Re) sulphide,
      bone scans using 99Tcm-labelled oxidronate, 111In-octreotide scans, 111In
      labelled leukocyte studies and cardiac reinjection studies using 201Tl. The
      maximum dose rates at 0.1 m were those from MUGA studies (167.3 microSv.h-1) and
      myocardial perfusion studies (one-day protocol = 391.7 microSv.h-1, two-day
      protocol = 121.8 microSv.h-1). The implications of these dose rates on both
      technical and nursing staff are assessed. Also, the dose received by an infant in
      close contact with a parent following a nuclear medicine investigation was
      estimated.

PMID- 10088170
TI  - Reductions in finger doses for radiopharmaceutical dispensing afforded by a
      syringe shield and an automatic dose dispenser.
AB  - A gamma extremity monitoring system (GEMS) has been used to measure finger doses
      during radio-nuclide dispensing procedures. GEMS uses a small semi-conductor
      probe that can be attached to a finger from which a continuous read-out can be
      obtained that is related to dose rate. The pattern of dose accumulation can be
      analysed to allow doses received from individual operations within a procedure to
      be evaluated. GEMS has been used to compare the radiation dose reduction afforded
      by a syringe shield and an automatic dose dispenser. Dispensing procedures were
      simulated using 10% of the activity normally administered in order to avoid
      problems with detector saturation. Results show that the syringe shield and the
      automatic dose dispenser reduced finger doses by more than a factor of 10 for the
      procedures tested. The disadvantages of the automatic dispenser tested were a
      failure to transfer activity in 10% of cases and a longer time taken for the
      dispensing process. GEMS has the potential to facilitate greater optimization of
      finger doses through analysis of finger dose patterns.

PMID- 10088171
TI  - Assessment of abstracts submitted for the 1998 BNMS annual meeting: concordance
      or lottery?
AB  - The selection of abstracts for presentation at the Annual Meeting of the British
      Nuclear Medicine Society is an arduous task for the assessors. It is only to be
      expected that assessors' appreciation of an abstract will be biased by their
      interests and knowledge. This study assessed the concordance between the marks
      awarded by specialist and general assessors for the 173 abstracts submitted to
      the 1998 Spring BNMS meeting. The results showed considerable agreement among the
      markers for most comparisons. We conclude that the current combination of
      specialist assessors evaluating specific sections and three generalists assessing
      all abstracts appears to be working well.

PMID- 10088172
TI  - Reproducibility of 99Tcm-MAG3 clearance.

PMID- 10088173
TI  - Modulatory proteins and processes in alliance with immune cells, mediators, and
      extracellular proteins in renal interstitial fibrosis.
AB  - A synopsis of the many aspects and factors that contribute to renal tubulo
      interstitial fibrosis is presented. The role of fibrogenic cytokines and the
      conversion of fibroblasts to myofibroblasts are described. It is emphasized that
      oxygen radicals cause fibroblasts to generate collagen. The properties of those
      accessory modulatory proteins that affect the behavior of cells in the
      interstitium are considered and how matrix for ensuing fibrosis is laid down.
      Understanding the extracellular matrix proteins and these modulatory proteins is
      important because their behavior can now be modified by means of antisense
      oligonucleotides.

PMID- 10088174
TI  - Ischemic preconditioning attenuates functional, metabolic, and morphologic injury
      from ischemic acute renal failure in the rat.
AB  - Ischemic preconditioning has been shown to ameliorate injury due to subsequent
      ischemia in several organs. However, relatively little is known about
      preconditioning and the kidney. To address this, rats were randomized to control
      (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of
      ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min
      periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of
      bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower
      serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats
      compared with C. Histology was examined in the C and P2, 3 groups and
      demonstrated less severe injury in the P2, 3 group. To gain insight into the
      mechanism by which preconditioning ameliorated ischemic injury, we performed near
      IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2,
      3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin
      during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar
      during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These
      data suggest that ischemic preconditioning may ameliorate ischemic renal injury
      as assessed by functional, metabolic and morphological methods. The mechanism(s)
      by which this occurs requires additional study.

PMID- 10088175
TI  - Effect of allopurinol in the course of adriamycin induced nephropathy.
AB  - The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3
      mg/kg) has been studied by blocking superoxide synthesis through the
      administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI),
      allopurinol administration was started 3 days prior to nephropathy induction and
      continued until day 14. In Experiment II (EII) allopurinol administration was
      started 2 weeks after nephropathy induction and was maintained until the end of
      the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial
      lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In
      EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed
      from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39
      mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24
      h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were
      observed and TILI medians were not different in both nephrotic groups at week 2
      (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II
      presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23
      mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic
      groups, there was no statistical difference in the median of affected glomeruli
      (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus,
      allopurinol was associated with a transient reduction in proteinuria and it did
      not alter the progression of the nephropathy.

PMID- 10088176
TI  - Oxidative stress in chronic renal failure.
AB  - This study focuses on the oxidative stress in patients with severe chronic renal
      failure who are not undergoing dialysis treatment. The erythocyte levels,
      creatinine clearing and plasma- and cell activities of the following enzymes were
      determined: glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase
      (CAT), glutathione reductase (GR), and glutathione transferase (GT). The
      concentrations of non-enzyme molecules such as total glutathione in both oxidized
      and reduced forms, and malonyldialdehyde (MDA) were also measured. The obtained
      values were compared with those in healthy blood donors of comparable age and
      social status. The results indicate that chronic renal patients have lower
      glutathione levels and reduced activities of glutathione peroxidase and of
      glutathione reductase, while exhibiting elevated levels of malonyldialdehyde and
      activities of superoxide dismutase, glutathione transferase, and catalase.
      Finally, creatinine clearing was found to be correlated (p < 0.001) to total
      (oxidized and reduced) glutathione, Gpx and MDA. These observations may serve to
      establish a simple protocol for evaluation of renal function.

PMID- 10088177
TI  - Differentiation of acute renal failure and chronic renal failure by 2-dimensional
      analysis of urinary dipeptidase versus serum creatinine.
AB  - The differential diagnosis of acute renal failure (ARF) and chronic renal failure
      (CRF) may be possible by measuring urinary dipeptidase (Udpase) activity and
      serum creatinine (Scr) concentration. When the mass test of 246 individuals was
      examined on a 2-dimensional plot of Udpase (y-axis) versus Scr (x-axis) with the
      data obtained from healthy volunteers (n = 189), ARF (n = 19) and CRF (n = 38)
      patients, the characteristic distribution of each group was obvious. It is
      summarized by the mean values of healthy volunteers (1.44 +/- 0.39 mg/dL, 1.19
      (0.59 mU/mL), ARF (6.04 +/- 5.04 mg/dL, 0.12 +/- 0.08 mU/mL), and CRF patients
      (8.72 +/- 2.93 mg/dL, 0.81 +/- 0.44 mU/mL). The healthy volunteers are
      distributed along the y-axis and the ARF patients the x-axis, thus separating the
      two groups 90 degrees apart. The CRF patients are scattered away from both x-,
      and y-axis. This 2-dimensional approach is thought to be very useful for the
      differential diagnosis of ARF suggesting Udpase as a new member of the marker
      enzymes of renal disease.

PMID- 10088178
TI  - Analysis of factors influencing chronic renal failure progression.
AB  - One of the most important characteristics of chronic renal failure (CRF) is its
      progression to end stage renal disease. CRF progression depends of many factors
      indicated in numerous experimental and clinical studies. The present study was
      undertaken with the aim to examine the role of sex, etiology of CRF, renal
      function at the beginning of the study, hypertension and protein intake on CRF
      progression. Ninety-two patients (47 female and 45 male) aged between 17 and 70,
      with various underlying kidney diseases and various degrees of CRF were followed
      for 8 years. CRF progression was expressed as Creatinine clearance (CCr) and
      reciprocal values of serum Creatinine (SCr) against time. CRF progression was
      slower in women than in men, but not significantly. Patients with diabetic
      nephropathy (b = 0.00006) and glomerulonephritis (b = 0.00005) had faster
      progression of CRF than patients with nephrosclerosis (b = 0.00002),
      tubulointerstitial nephritis (b = 0.00003) and polycystic kidney disease (b =
      0.00003). The fastest progression of CRF was in patients with the lowest SCr
      values at the beginning of the study. Proper regulation of blood pressure was the
      most important factor in slowing down CRF progression, independently of kind of
      antihypertensive drugs. Neither angiotensin converting enzyme inhibitors (b = 
      0.00001) nor calcium channel blockers (b = -0.00002) showed better effects on CRF
      progression slowing down in comparison with other antihypertensive drugs (b = 
      0.00001). Low protein diet slowed down CRF progression, but not significantly. In
      conclusion, our retrospective study confirms that CRF progression depends on sex,
      underlying renal diseases and serum Creatinine levels at the beginning of the
      study. Good regulation of blood pressure and low protein diet can slow down CRF
      progression.

PMID- 10088179
TI  - Chloroquine influences renal function in rural Zimbabweans with acute transient
      fever.
AB  - To establish the effects of chloroquine on kidney function we monitored renal
      parameters in age and sex matched control subjects and patients who presented
      with acute transient fever. The patients were immediately treated with
      chloroquine diphosphate in the recommended dosage. Blood samples for creatinine,
      urea, Na+ and K+ determinations were collected before treatment (Day 0), on the
      3rd day of treatment (Day 3) and two days after the last dose of chloroquine (Day
      5). 24 h urine collections were collected for five consecutive days from the
      second day of treatment. Spot urine samples showed the absence of blood cells,
      bilirubin, glucose, protein and ketones. Examination of thick blood smears over
      three days did not reveal any forms of malaria parasites. Urinary tract infection
      in the patients was also excluded. Therefore, these patients were a suitable
      group to assess the effects of chloroquine on renal function. The blood pressure
      in females and males decreased significantly after two days of chloroquine
      treatment compared with Day 0. The plasma concentration of creatinine in females
      and females was increased by chloroquine 2 days after the last dose by comparison
      with the Day 0 (females, 66 +/- 2 mumol/L versus 83 +/- 2 mumol/L n = 20, p <
      0.01 and males, 78 +/- 6 mumol/L versus 81 +/- 9 mumol/L, n = 20, p < 0.01). This
      was paralleled by a reduction in urinary creatinine excretion during the same
      period (females 15 +/- 1 mg/kg body weight/24 h versus 12 +/- 1 mg/kg body
      weight/24 h and males 23 +/- 3 mg/kg/24 h versus 18 +/- 2 mg/kg/24 h, p < 0.01 in
      both instances). Urinary urea excretion in females was reduced from 290 +/- 6
      mumol/kg/24 h to 215 +/- 5 mumol/kg/24 h 2 days after treatment. The results of
      the study suggest that the effects of chloroquine in patients with acute
      transient fever include lowered urinary urea and creatinine excretion.

PMID- 10088180
TI  - Long-term effects of small doses of calcitriol in hemodialysis patients with
      moderate secondary hyperparathyroidism.
AB  - Prevention of secondary hyperparathyroidism (SHPTH) and treatment of the moderate
      cases by small p.os doses of Vitamin D has not been thoroughly investigated on
      the long term, while large doses of Vitamin D have been successful in the short
      term treatment of this entity. We administered calcitriol p.os 0.5-1.0 microgram,
      according to iPTH levels, after each dialysis session, in 19 patients (group A)
      for 36 months. They were ten men and nine women, 63 years old (43-81), with iPTH
      levels > 4N (419 +/- 185 pg/mL). Seven adenomas were found in five of them (group
      A1). Serum Ca, phosphate (P) and alkaline phosphatase (AP) were measured every 15
      30 days. Serum iPTH and aluminum as well as echogram or scanning of the
      parathyroid glands were checked every 6 months. Ten additional dialysis patients,
      seven men and three women, 54.5 years old (36-68), non-significantly different to
      group A in iPTH levels (290 +/- 225 pg/mL) with three adenomas in two of them
      (group B1) received no calcitriol and served as controls (group B). Calcitriol
      treatment significantly lowered serum iPTH levels in group A patients (from 419
      +/- 185 to 173 +/- 142 pg/mL, p < 0.0001, delta iPTH: -246 +/- 161 pg/mL); iPTH
      remained stable in group B patients (delta iPTH: +7.9 +/- 116 pg/mL) with an
      intergroup significant difference at P < 0.0001. All other parameters measured
      did not show any significant change. No significant correlation of iPTH to Ca, P
      or AP was found in A. Initial iPTH levels were higher in A1 and B1 patients and
      decreased by calcitriol in A1 group. Adenomas in A1 patients did not change in
      number and size in contrast to B1 where new adenomas appeared (5 patients, 10
      glands). Small doses of vitamin D lower high iPTH levels and prevent parathyroid
      gland hyperplasia. Existing hypertrophy is stabilized under calcitriol treatment
      both morphologically and biologically.

PMID- 10088181
TI  - Rehabilitating role of glutathione ester on cisplatin induced nephrotoxicity.
AB  - Cisplatin caused differential toxic effects on blood glucose and plasma urea,
      uric acid and creatinine levels. Cisplatin also showed an inhibitory effect on
      kidney marker enzymes like alkaline phosphatase, acid phosphatase, aspartate
      aminotransferase and alanine aminotransferase. However, administration of
      glutathione ester modulates the toxic side effect of cisplatin observed in kidney
      enzymes, and in blood parameters. It seems that glutathione ester plays an
      important role in protecting against the cisplatin induced nephrotoxicity by
      inhibiting the accumulation of platinum in kidneys.

PMID- 10088182
TI  - Ethylene dibromide poisoning with acute renal failure: first reported case with
      non-fatal outcome.
AB  - Ethylene-di-bromide is a popular fumigant. Delayed long-term effects of this
      chemical include carcinogenicity and genotoxicity in animals. Only a few cases of
      acute ethylene-di-bromide toxicity have been reported and all of them have
      resulted in a fatal outcome. We report the first case of ethylene-di-bromide
      poisoning presenting with acute renal failure and toxic hepatitis that was
      managed successfully.

PMID- 10088183
TI  - Religious reasons for discontinuation of immunosuppressive medications after
      renal transplant.
AB  - It is commonly believed that religion has no influence on medication compliance.
      We present a case in which belief in faith healing led to discontinuation of
      immunosuppressive medications after renal transplantation. Conflict occurs when
      patients believe they are healed but experience continued illness. Religious and
      spiritual beliefs should be assessed pre- and post-transplant, and efforts made
      to encourage medication compliance.

PMID- 10088184
TI  - Renal tubular acidosis, hypokalemic paralysis, rhabdomyolysis, and acute renal
      failure--a rare presentation of Chinese herbal nephropathy.
AB  - We encountered a 66-year-old Chinese man presented with hypokalemic paralysis,
      rhabdomyolysis and acute renal failure after administration of mixed Chinese
      herbs. Proximal renal tubular acidosis and selective glucosuria were the main
      tubular dysfunctions. The renal failure recovered smoothly and rapidly after
      resuscitation and the tubular function abnormalities regained spontaneously after
      medicine withdrawal. It should be recognized that renal tubular acidosis with
      hypokalemic paralysis, rhabdomyolysis and subsequent acute renal failure may
      develop after taking Chinese mixed herbal medicine.

PMID- 10088185
TI  - Treatment of acute renal failure with antioxidant vitamin E.

PMID- 10088186
TI  - [The Bimler method in the treatment of sagittal shift of the skeletal base in
      Class II division 1 malocclusion].
AB  - Inadequate sagittal development of the mandible (class II, division 1
      malocclusion), is one of the most frequent in dentofacial malformations. We
      present the Bimler "gebissformer", removable and functional appliance and its
      tridimensional action. The treatment can be started during the deciduous
      dentition or in mixed dentition. Therapeutic results, increase of SNB angle,
      maxillary expansion, and reduction of the deep bite are presented. While
      therapeutic failure is observed in 30% of the cases (by absence of tissular
      response or poor patient compliance), the stability of the results in 70% of the
      remaining cases and its total inocuity make this appliance an interesting method
      of treatment.

PMID- 10088187
TI  - [A comparison of standard radiographs and "scout-view" radiographs. The value for
      cephalometric analysis].
AB  - Is the scout-view as reliable as the standard lateral view for cephalometric
      analysis? Cephalometric data (Delaire analysis) were obtained in ten patients
      with CT-scan and standard x-ray for comparison. Qualitative results showed
      imprecisions for craniofacial contours and soft tissue ptosis. Quantitative
      results were analyzed statistically and revealed a significantly higher level of
      error with scout-view tracings. The scout-view does not appear to be as reliable
      and takes longer to acquire than the standard lateral x-ray: for the pediatric
      population, it could be a disadvantage.

PMID- 10088188
TI  - [Precision control of the position of the bone segments during surgical
      navigation].
AB  - The Surgical Segment Navigator (SSN) which has been developed together with Carl
      Zeiss at the department for craniomaxillofacial surgery at the University of
      Regensburg, is the first system for highly precise positioning of bone segments.
      Before clinical application, the precision of the SSN was evaluated by navigation
      of cadaver bone segments which is presented in this paper. The SSN tracks
      intraoperatively bone segments and displays the osteotomied segments on a monitor
      of the SSN-workstation. All movements are documented and saved within a computer
      file. Thus, the SSN makes the quality assurance of intraoperative positioning of
      bone segments possible.

PMID- 10088189
TI  - [Combination of successive free transplants and osseointegrated implants in the
      reconstruction of the upper jaw].
AB  - Various free flap transfers can be associated to reconstruct a defect after
      resections in the head and neck region. The use of these flaps can be synchronous
      (one-stage surgery) or metachronous (two-stage surgery) in order to correct or
      improve secondary residual deformities. A two-stage use of free flaps, first with
      an osteocutaneous scapular flap and second with a fascial radial forearm flap, is
      reported after total maxillectomy. The osteocutaneous scapular flap was used to
      restore function (swallowing, chewing, speech and cheek projection) and the
      radial forearm flap to improve esthetic facial morphology. Minor ancillary
      procedures were subsequently necessary to achieve the final result (brow lift,
      tarsal straightening and facial lift).

PMID- 10088190
TI  - [Osteoradionecrosis of the jaws. Apropos of 7 cases].
AB  - Jaw osteoradionecrosis (ORN) is one of the most serious complications of cervico
      facial cancer irradiation. Severity is related to major bone lysis and the
      difficult medical and surgical treatment. We report our experience in seven cases
      over a ten-year period. Mandibular localization was predominant (85%). The mean
      age of the patients was 36 years. The average delay to development of ORN was 5.5
      years. The treatment was medico-surgical, based on wide surgical exeresis (6/7),
      frequently via endobuccal surgical approach (4/7). Prevention remains the best
      treatment of ORN associated with an accurate management of all patients who need
      radiotherapy.

PMID- 10088191
TI  - Descending necrotizing mediastinitis caused by odontogenic infections.
AB  - Intrathoracic dissemination of an odontogenic infection is very infrequent. The
      resulting clinical manifestation, known as descending necrotizing mediastinitis,
      causes high mortality. Due to the absence of early clinical or radiological
      signs, diagnosis is usually made only when the process is completely established.
      Treatment is a combination of intravenous antibiotics and mediastinal drainage,
      via either a cervical or a transthoracic approach. We report the clinical and
      microbiological characteristics of 4 patients with descending necrotizing
      mediastinitis, and their clinical course over a period of 10 years.

PMID- 10088192
TI  - [Congenital stenosis of the piriform aperture: a cause of respiratory distress in
      newborn infants. Review of the literature, from 2 cases].
AB  - Congenital nasal pyriform aperture stenosis is a rare cause of neonatal airway
      obstruction. Computed tomography confirms the diagnosis and delineates the
      anomaly. This abnormality can be isolated or associated with abnormalities of the
      midface. The two options are surgical or medical treatment. The surgical
      treatment usually used is a surgical enlargement of the nasal pyriform aperture
      via a sublabial approach. We report 2 cases of congenital nasal stenosis treated
      successfully by an inter-maxillary disjunction followed by an expandable palatal
      plate. This simple and low morbidity technique allowed a durable transversal
      augmentation of the pyriform apertures.

PMID- 10088193
TI  - [Oral aphthae induced by nicorandil. Anatomopathologic aspects. Apropos of a
      case].
AB  - Major apthous stomatitis induced by nicorandil is exceptional, the mechanism is
      still unknown and the histological aspect of these lesions have not been
      previously reported. Our case reports a man who was treated by nicorandil for
      coronary artery disease. He was referred for major aphtous stomatitis; one
      element was biopsied. The histological aspect was an aspecific sialadenitis, with
      granulous reaction, and without vasculitis or eosinophilic infiltration. We
      conclude that aphtous stomatitis induced by nicorandil could to be explain by a
      toxic effect, rather than a toxicallergic or immunologic mechanism.

PMID- 10088194
TI  - [Cervical ganglioneuroma. Review, apropos of a case].
AB  - We describe a case of cervical ganglioneuroma, an uncommon benign tumor which
      develops slowly, predominantly in females and infants. Ganglioneuromas have a
      neuroectodermic origin and are localized along the sympathetic trunk. Most are
      unmasked fortuitously by palpation or by high serum catecholamine levels
      proportional to tumor size. After radiographic exploration and surgical excision,
      a pathologic study of the surgical specimen is required to identify this very
      differentiated tumor stemming from the neural crest.

PMID- 10088195
TI  - [Palpebral capillary hemangioma and amblyopia. Apropos of 2 cases].
AB  - Periorbital capillary hemangiomas of childhood can produce visual axis occlusion
      and anisometropia, resulting in amblyopia. We report our experience performing
      surgical resection of periorbital capillary hemangiomas. Partial resection of
      hemangiomas was performed in two infants under five months of age, and permitted
      clearing of the visual axis. This immediate effect is necessary to prevent
      amblyopia. Surgical resection should be considered a treatment option for
      managing periorbital capillary hemangiomas which threaten vision.

PMID- 10088196
TI  - A population-based study of plasma cyclic guanosine monophosphate: relations to
      age, atrial natriuretic factor and angiotensin-converting enzyme activity.
AB  - In order to study the relations between plasma cyclic guanosine monophosphate
      (cGMP) and anthropometric variables, plasma atrial natriuretic factor (ANP) and
      serum angiotensin-converting enzyme activity (ACE), a population study with
      random selection of 217 subjects (49% men) 18-69 years old was performed. Venous
      blood was drawn at 08.00 h and ambulatory blood pressure (ABP) recording was then
      performed. There was no gender-difference in cGMP levels (men 2.2 +/- 1.1 nmol L
      1, women 2.2 +/- 1.1 nmol L-1). A weak negative correlation was seen between cGMP
      and systolic ABP in both genders 20-44 years of age (r = -0.3, p = 0.05 for
      both), but this correlation did not persist in multivariate analysis with
      correction for ANP, age and ACE. In women, cGMP correlated positively with ANP (r
      = 0.27, p = 0.005) independently of ANP, ACE, ABP and age. ACE correlated
      negatively with cGMP in men (all; r = -0.22, p = 0.03, 45-69 years of age r = 
      0.49, p = 0.0002) and this correlation was independent of ANP, ACE, ABP and age.
      ACE catalyses the breakdown of bradykinin, which stimulates the release of NO. As
      the second messenger of NO is cGMP, the negative correlation between ACE and cGMP
      in men might be a reflection of reduced production of NO. Our results also
      suggest that there are gender differences in the stimuli for basal cGMP
      production.

PMID- 10088197
TI  - Evaluation of a new urinary amylase test strip in the diagnosis of acute
      pancreatitis.
AB  - We have developed a novel rapid test strip for detecting pancreatic amylase in
      urine and prospectively evaluated its accuracy in screening for acute
      pancreatitis (AP). The test strip is based on the immunochromatography principle
      and uses two monoclonal antibodies specific for pancreatic amylase. Urine samples
      were collected from 500 consecutive patients with acute abdominal disease (52
      with AP) and prospectively tested with the strip. The accuracy of the test strip
      was compared with that of two quantitative urine amylase determinations and a
      urinary dipstick test for amylase (Rapignost). Sensitivity of the test was 69%
      and specificity was 97% in differentiating patients with AP from those with acute
      abdominal extrapancreatic disease at admission. The negative predictive value was
      0.986. The test showed moderate agreement both with an assay measuring total
      amylase activity and with another measuring pancreatic amylase immunoreactivity.
      At similar high specificity (97%), quantitative determination of total amylase
      activity (cut-off 3960 U/L) and pancreatic amylase (cut-off 2180 micrograms/L)
      showed lower sensitivity (54% and 41%) than the test strip (69%). The test is
      specific and rapid to perform, and it rules out AP with high probability. It
      could therefore be useful in an emergency setting without laboratory facilities
      in the differential diagnosis of acute abdominal pain.

PMID- 10088198
TI  - Red blood cell rigidification during cyclosporin therapy: a possible early
      warning signal for adverse reactions.
AB  - In a previous retrospective study with kidney-transplant patients,
      immunosuppressive treatment with Cyclosporin A (CsA) was found to be associated
      with impaired red blood cell (RBC) deformability. The aim of the present study
      was to evaluate and substantiate a possible causal relationship between the use
      of CsA and its effect on RBC deformability in a prospective study on non
      transplant patients. Blood samples of 12 patients with psoriasis were taken
      before and after 2, 4, 8, 12 and 16 weeks of treatment with CsA (3-5 mg/day). Red
      cell deformability, expressed as Elongation Index (EI), was measured with the
      Laser-assisted Optical Rotational Cell Analyzer (LORCA), a new ektacytometric
      instrument. Mean values +/- SD for EI found after 16 weeks of treatment with
      cyclosporin (0.570 +/- 0.008) were significantly (p < 0.001) lower than the value
      before treatment (0.589 +/- 0.011). A dose-response relation could not be
      established within the small range of CsA doses used in this study. Irrespective
      of the dose, however, a significant correlation (r = -0.55; p = 0.0001) between
      duration of treatment and decrease in EI was demonstrated. In vitro incubation of
      blood with cyclosporin was not able to reproduce this effect, suggesting that a
      direct effect of the drug on RBCs is unlikely. Despite its use in relatively low
      doses, CsA causes a reduction in RBC deformability, an effect that increases
      during the course of treatment. It is suggested that this slow, but continuously
      increasing, RBC rigidification plays a role in the early pathogenesis of the
      adverse nephrotoxic complications frequently associated with this
      immunosuppressive regimen.

PMID- 10088199
TI  - Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long
      lasting contraction to endothelin-1 in the porcine coronary artery.
AB  - In the coronary circulation, endothelin-1 (ET-1) evokes spasms which are
      difficult to treat when the endothelial integrity is compromised. This study
      compares several classes of relaxing agents on already established contractions
      to ET-1 in an in vitro model using ring segments of the porcine left descending
      coronary artery (pLAD). All segments were precontracted with 10 nmol/L ET-1. The
      calcium channel blocker isradipine was 300 times more potent than verapamil, but
      was only a partial relaxant; the maximal relaxation obtained was 52 +/- 2% (n =
      6). Atrial natriuretic peptide (ANP) was an equally potent relaxant of the ET-1
      contraction; however, it too was an incomplete relaxant, maximal relaxation being
      < 60%. A 50% relaxation of the ET-1 contraction was obtained with 0.28 +/- 0.24
      mumol/L ANP, n = 4 (IC50). Comparison of cyclic nucleotide analogues revealed a
      30 times higher potency for 8-bromo-cyclic guanosine monophosphate (8-Br
      cGMP)(IC50 44 +/- 11 mumol/L, n = 6) than for 8-bromo-cyclic adenosine
      monophosphate (8-Bi-cAMP) (IC50 1600 mumol/L, n = 6). The cyclic nucleotide
      phosphodiesterase (PDE) inhibitor milrinone, a PDE 3-inhibitor with an IC50 2.4
      +/- 1.8 mumol/L, (n = 6) was 10 times more potent than rolipram (PDE 4
      inhibitor), zaprinast (PDE 5-inhibitor) and vinpocentine (PDE 1-inhibitor).
      Withdrawal of these analogues and inhibitors from segments continuously exposed
      to 10 nmol/l ET-1 revealed that vinpocentine and 8-Br-cGMP were irreversible
      relaxants, in contrast to milrinone and 8-Br-cAMP. In conclusion, this study has
      demonstrated that cGMP-enhancing agents, such as the naturally occurring ANP, the
      calcium channel blocker isradipine, and the synthetic inhibitor of PDE 3, were
      the most effective relaxants of ET-1 evoked contractions in pLAD in vitro.

PMID- 10088200
TI  - Monounsaturated trans fatty acids, elaidic acid and trans-vaccenic acid,
      metabolism and incorporation in phospholipid molecular species in hepatocytes.
AB  - The incorporation of [14C]elaidic acid (trans18:1(n-9)) in phosphatidylcholine
      and phosphatidylethanolamine molecular species in isolated rat liver cells has
      been studied, and the results compared with the incorporation, previously
      published (B. Woldseth et al. Biochim Biophys Acta 1993; 1167: 296-302), of
      [14C]palmitic acid (16:0) and [14C]stearic acid (18:0) and with that of
      [14C]oleic acid (cis18:1(n-9)). The pattern of incorporation in phospholipid
      molecular species is similar to that of [14C]stearic acid and different from that
      of [14C]palmitic acid. In phosphatidylcholine [14C]trans18:1-18:2 and
      [14C]trans18:1-20:4 were the most abundant species, and in
      phosphatidylethanolamine [14C]trans18:1-20:4 was the predominant species. With
      increasing concentration of [14C]elaidic acid increasing amounts of
      [14C]trans18:1-[14C]trans18:1 were found. The total incorporation in
      phospholipids was less than that of [14C]stearic acid, but more than that of
      [14C]palmitic acid. The distribution in percent of [14C]elaidic acid in
      phospholipid classes was 8.8% in phosphatidylinositol, 1.8% in
      phosphatidylserine, 59.1% in phosphatidylcholine and 30.3% in
      phosphatidylethanolamine with 0.1 mmol l-1 substrate concentration. More
      [14C]elaidic acid than [14C]palmitic acid or [14C]stearic acid was oxidized. The
      incorporation in phospholipids of [14C]elaidic acid was very different from that
      of [14C]oleic acid. The main species with [14C]oleic acid were 16:0-[14C]cis18:1
      in phosphatidylcholine, and [14C]cis18:1-20:4 in phosphatidylethanolamine. In
      some experiments [14C]18:2(n-6) was incubated together with unlabelled elaidic or
      unlabelled trans-vaccenic acid (trans18:1(n-7)). In these experiments, more
      trans18:1-18:2 was formed from elaidic acid than from trans-vaccenic acid,
      especially in phosphatidylethanolamine.

PMID- 10088201
TI  - One-tube multiplex RT-PCR of BCR-ABL transcripts in analysis of patients with
      chronic myeloid leukaemia and acute lymphoblastic leukaemia.
AB  - We describe a one-tube multiplex reverse transcription polymerase chain reaction
      (RT-PCR) assay for the detection of bcr-abl fusion mRNA in analysis of patients
      with chronic myeloid leukaemia and acute lymphoblastic leukaemia. The assay
      provides a quick and reliable method for the detection and analysis of chromosome
      translocations resulting in formation of the fusion proteins p210 (b3a2/b2a2) and
      p190 (e1a2). The method is based on the use of magnetic beads and sequence
      specific reverse transcription primers. By combining direct mRNA isolation,
      reverse transcription and first-stage PCR we have reduced the number of
      manipulations, maintained sensitivity, and minimized the risk of contamination. A
      nested primer strategy is used to secure sensitivity. We also introduce a
      competitive one-tube RT-PCR to be able to monitor the relative quantity of
      transcripts using in vitro transcribed RNA as competitor.

PMID- 10088202
TI  - Response of serum total renin to ramipril and metoprolol in hypertensive
      patients.
AB  - Renin-angiotensin system has long been thought to be a classic endocrine negative
      feedback system in the pathophysiology of hypertension. Furthermore, angiotensin
      II formation was believed to be regulated by renin secreted from the kidneys. In
      contrast to these considerations is the identification of local angiotensin II
      production in other tissues than pulmonary vasculature. Prorenin, the molecular
      precursor of renin, has been assumed to be involved in local angiotensin II
      production because of its renin-like activity. Prorenin has also been found to be
      secreted from extrarenal sources, although a major part of it is derived from the
      kidneys. Increased concentration of total renin in serum has been proposed to be
      useful in identifying patients with active proliferative retinopathy in insulin
      dependent diabetic patients. Renin-angiotensin system is strongly affected by
      angiotensin-converting enzyme (ACE) inhibitors and therefore the interfering
      effect of ACE inhibitor medication on total renin concentration should be known
      in order to interpret serum total renin concentrations. Nine hypertensive
      outpatients, all men, treated at the department of internal medicine in Turku
      University Central Hospital, received randomly 5 mg of ramipril or 95 mg of
      metoprolol once a day for 4 weeks. Ramipril significantly increased the mean
      value of total renin (191.9 ng/l vs 312.0 ng/l, p < 0.01), but the metoprolol
      induced increase in the concentration of serum total renin was insignificant. We
      conclude that the negative feedback mechanism in regulating renin and prorenin
      secretion was inhibited by ACE inhibitor ramipril but beta 1-selective
      adrenoceptor antagonist metoprolol did not significantly change total renin
      concentration in serum.

PMID- 10088203
TI  - A modified fast micro method in agarose for isotype, allotype, light chain and
      idiotype-specific analysis of antibody clonotypes to bacterial virulence
      antigens.
AB  - A modified fast micro method for spectrotypic/clonotypic analysis of human IgG1-4
      antibodies against bacterial virulence antigens of polysaccharide or protein
      nature is described. Serum samples of as small volumes as 0.5 microliter were
      isoelectrically focused in micro agarose gels made in plexiglass matrices and
      blotted using immunoaffinity-mediated capillary blotting onto nitrocellulose
      membranes previously coated with antigen. The bands of the antigen-specific
      antibodies were identified with respect to isotypes, light chain types, allotypes
      or idiotypes by incubating the nitrocellulose membranes with mouse monoclonal
      anti-human IgG subclass antisera and then with alkaline phosphatase-conjugated
      rabbit anti-mouse immunoglobulins. The method was applied for characterization of
      human monoclonals against tetanus toxoid (TT) and for the analysis of variable
      patterns of clonotypes in IgG subclass-deficient patients. The usefulness of the
      technique was also demonstrated by comparing the variable specificity and
      reactivity of different commercial monoclonals against human IgG subclasses. This
      method is fast, specific, sensitive, uses little material, is simple and
      reproducible.

PMID- 10088204
TI  - How should blood rheology be measured in macroglobulinaemia?
AB  - Blood and plasma viscosity were measured in 13 patients with monoclonal
      macroglobulinaemia. Blood viscosity was measured at natural hematocrit and after
      adjustment to 45%. Studies were performed at three different temperatures, +24
      degrees C, +32 degrees C and +37 degrees C. Plasma viscosity was measured in a
      rotational viscometer and in a capillary tube at the above-mentioned
      temperatures. Blood viscosity was to some extent related to the patients'
      symptoms, whereas a correlation between blood and plasma viscosity became less
      pronounced with decreasing shear rates, indicating that plasma viscosity is not a
      perfect indicator of blood viscosity in macroglobulinaemia. It was shown that red
      cell concentration, besides the concentration of monoclonal immunoglobulins (=
      paraproteins (PP)), is an important determinant of blood viscosity. The
      correlation between red cell concentration and viscosity became stronger with
      decreasing shear rate. Whole blood viscosity at low shear rates seems to be the
      best indicator of rheological symptoms in patients with macroglobulinaemia. It is
      concluded that blood rheology in patients with macroglobulinaemia is best studied
      at +32 degrees C to +37 degrees C in whole blood and at low shear rates.

PMID- 10088205
TI  - Lack of relationship between serum and gallbladder bile calcium in patients with
      gallstone disease.
AB  - BACKGROUND: Recent studies suggest that alternation in serum calcium influences
      the level of gallbladder bile ionized calcium (Ca2+). Theoretically, this could
      increase the risk of calcium precipitation in the gallbladder. METHODS: We
      therefore measured serum and gallbladder bile minerals in patients with
      gallstones (n = 27) and without (n = 10, controls). The serum samples were taken
      just prior to induction of anaesthesia and gallbladder bile was aspirated before
      any manipulation of the gallbladder. RESULTS: The active molality of Ca2+ in
      gallbladder bile was not statistically significant different between cases and
      controls (0.44 +/- 0.16 vs. 0.40 +/- 0.10 mmol/kg), whereas pH was significantly
      lower (6.94 +/- 0.31 vs. 7.36 +/- 0.28, p < 0.0001) and cholesterol higher (4.37
      +/- 2.70 vs. 1.79 +/- 1.33 mmol/l; p < 0.01) in gallbladder bile obtained from
      cases. Serum Ca2+ at actual pH, magnesium and phosphate were significantly higher
      among cases than in controls. Gallbladder bile active molality of Ca2+ was
      significantly correlated with bile total calcium in both groups (r = 0.72; p <
      0.001 and r = 0.91; p < 0.001, respectively). In controls only, we observed a
      positive relationship between serum Ca2+ at actual pH and the active molality of
      Ca2+ in bile (r = 0.61; p < 0.05). CONCLUSION: Our study demonstrates that Ca2+
      in gallbladder bile does not differ between cases and controls. The lack of
      correlation between serum and gallbladder bile constituents in cases compared to
      controls suggests that changes in calcium equilibration between bile and serum in
      patients with gallstone disease might be of importance for the formation of
      gallstones.

PMID- 10088206
TI  - An experimental study of cardiac natriuretic peptides as markers of development
      of congestive heart failure.
AB  - The use of cardiac peptide measurements as possible diagnostic tools in
      congestive heart failure has been extensively discussed in the recent literature.
      Therefore, the aim of this study was to establish a model of experimental chronic
      heart failure, and thereby perform a comparative study of secretion and
      circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N
      terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic
      peptide (BNP) during evolving heart failure. Chronic heart failure was induced in
      seven pigs by rapid left atrial pacing for three weeks. The effects of failure
      induction were documented 24 h after pacemaker deactivation. Hemodynamic indices
      of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right
      atrial pressure (RAP), were all considerably increased compared to sham operated
      controls. Likewise, plasma endothelin-L, noradrenaline, renin activity,
      aldosterone and angiotensin II were all markedly increased. Heart failure was
      accompanied by significant increases in both estimated cardiac secretory rate and
      plasma concentrations of all three cardiac peptides, significantly correlated to
      the PCWP. The directional changes during evolving heart failure were similar,
      although the percentage increase in plasma BNP was much larger than for ANP and N
      terminal proANP. In absolute molar terms, however, the BNP concentration changes
      were minor compared to those of the other two peptides. The larger percentage
      increase of BNP might indicate its superiority as a marker of heart failure
      development, provided a functional assay suitable for clinical use can be
      designed for a peptide circulating in this low concentration range.

PMID- 10088207
TI  - Markers of myocardial injury in blood following PTCA: a comparison of CKMB,
      cardiospecific troponin T and troponin I.
AB  - In 74 patients undergoing elective PTCA, CKMB, cTnT, cTnI-Access (cTnI-Acc) and
      cTnI-Abbott (cTnI-Abb) were measured in serum before and days 1 and 4 after the
      procedure. Two of the patients had pronounced biochemical evidence of AMI. In
      addition, a minor to moderate increase in CKMB, cTnT, cTnI-Acc and cTnI-Abb were
      found on day 1 in 13, 22, 18 and 25 patients, respectively. Excluding the two
      with AMI, cTnT was also increased on day 4 in 16 patients and cTnI-Abb in 15
      patients, whereas CKMB and cTnI-Acc levels were essentially normal in all. Thus,
      an unexpected discrepancy between the two methods for cTnI was revealed on day 4.
      In these 16 patients, there was no statistically significant relationship between
      the level of cTnT on day 4 and the levels of CKMB or cTnI-Acc on day 1. This is
      in contrast to a significant correlation to cTnT and cTnI-Abb on day 1. Based on
      these results, it is speculated that the marker levels on day 1 are due to
      reversible as well as irreversible damage, whereas cTnT and cTnI-Abb on day 4
      more selectively reflect the degree of myocardial necrosis. cTnT and TnI-Abb on
      day 4 are therefore proposed as valuable markers for further study of the
      clinical implications of myocardial damage following PTCA and related
      interventions.

PMID- 10088208
TI  - The human food safety evaluation of new animal drugs.
AB  - The pre-approval risk assessment process for new animal drugs is described in
      this article. The toxicological and residue chemistry data needed by the FDA for
      the human food safety evaluation of a new animal drug is also discussed.

PMID- 10088209
TI  - Monitoring adverse reactions to veterinary drugs. Pharmacovigilance.
AB  - The Food and Drug Administration Center for Veterinary Medicine (CVM) monitors
      reports of adverse drug experiences (ADE) for animal drug products, medicated
      feeds, and veterinary devices. The term most frequently applied to this
      monitoring activity is pharmacovigilance. An ADE is either an undesired effect or
      the lack of a desired effect. During 1997, the CVM received over 4,000 reports.
      Every report is evaluated by a veterinarian using an algorithm and entered into a
      computer database. In instances where public or animal health is judged to be at
      risk, the initial review leads to follow-up activity. The final result can be a
      product safety communication, change in labeling, or in rare circumstances,
      removal of the product from the market or even withdrawal of FDA approval to
      market the product. The purpose of this article is to provide a brief description
      of the pharmacovigilance program for animal drugs in food-producing animals, and
      answer some of the more commonly received questions about adverse experience
      reporting.

PMID- 10088210
TI  - Health implications of residues of veterinary drugs and chemicals in animal
      tissues.
AB  - The animal drug approval process in the United States is based upon the premise
      that the presence of drug residues in meat and poultry above tolerance is a
      public health hazard. Tolerances represent the maximum level of concentration of
      antimicrobials permitted in animal tissues at the time of slaughter. The
      tolerances are intended to ensure that residual drugs will have no harmful
      effects if ingested. The purpose of this article is to present existing evidence
      of the acute and chronic health consequences that may occur because of food of
      animal origin contaminated with illegal residues above the tolerance. The impact
      of food-borne drug residues on the gut microflora, residue detection limitations,
      and the responsibility of the veterinary practitioner in ensuring food safety is
      discussed.

PMID- 10088211
TI  - Federal surveillance of veterinary drugs and chemical residues (with recent
      data).
AB  - The National Residue Program is a dynamic risk-based program involving many
      Federal agencies, with the objective of preventing illegal drug residues and
      chemicals in the food supply. Surveillance is the systematic collection,
      analysis, and interpretation of residue data for public health action. This
      consists of assessing the cause(s) of the problem, recommending educational
      incentives, and intervention of prevention and control measures. The role of
      residue databases in formulating policy decisions and identifying risk factors
      for drug residues is discussed. A descriptive analysis, of 5 years (1992-1996)
      field investigative reports of drug residue occurrence in food animals is
      presented. The results showed that violative residues occurred predominately in
      culled dairy cows and bob veal calves.

PMID- 10088212
TI  - The national milk safety program and drug residues in milk.
AB  - There are a number of factors that must be considered in any attempt to control
      animal drug residues in milk and milk products. Dairy herds vary greatly in
      number of cows. Milk from individual cows and farms is pooled, diluting drug
      residues that may be present in the milk from a single treated cow. Management
      techniques, including the handling, administration, and record keeping of animal
      drugs, vary greatly from one dairy to another. It is important that both
      veterinarians and nonveterinarians adhere to adequate milk discard times for
      animal drugs used to treat dairy animals. Observance of appropriate safeguards at
      the farm level, such as record keeping and clearly identifying treated animals,
      is critical for controlling and preventing the presence of illegal animal drug
      residues. Within the framework of the Federal Food, Drug, and Cosmetic Act and
      the Public Health Service Act, the FDA is working with state and other regulatory
      agencies and industry to better ensure the absence of illegal animal drug
      residues in milk and milk products. Preventive measures concentrate on minimizing
      the need to administer animal drugs to lactating cows, and diverting milk
      containing drug residues from the human food supply. Monitoring programs
      concentrate on screening milk and tracing violations to the individual producer.
      Minimizing illegal drug residues in milk and milk products requires close
      cooperation between farmers, veterinarians, the dairy industry, the
      pharmaceutical industry, and regulators.

PMID- 10088213
TI  - The Food Animal Residue Avoidance Databank (FARAD). Past, present and future.
AB  - During the last one-and-one-half decades, FARAD has established an unparalleled
      compilation of residue and pharmacokinetic information for veterinary species. In
      order to fulfill its mission, FARAD has become as much a research project as an
      educational one. Pressing problems, such as disease-altered kinetics, minor
      species drug use, and industrial contaminants in livestock, require the new
      methods of analysis FARAD is developing. The data upon which this work is based
      can be greatly augmented by participation by other nations. In the United States,
      it was the cooperation of both academic and regulatory organizations that made
      the success of FARAD possible. Similar international cooperation can facilitate
      use of the FARAD model in other countries for the economic benefit of all
      participants, enhancement of food safety, and promotion of animal welfare.

PMID- 10088214
TI  - Regulatory approaches for controlling pesticide residues in food animals.
AB  - Pesticide use is vital to the production of an economical, high-quality food
      supply throughout the world. The regulatory system in the United States is
      designed to prevent the entry of unacceptable residues into the food supply. To
      address the complexities associated with pesticide use, the regulatory apparatus
      is composed of several federal and numerous state agencies. Based on monitoring
      results, it appears that most pesticides are being used in the appropriate manner
      and that thresholds for pesticides, deemed to be adequate to protect human
      health, are seldom exceeded. With our increasing knowledge of the public health
      and ecologic threats posed by pesticide residues, our approach to regulating
      pesticides will continue to evolve.

PMID- 10088215
TI  - PBBs, PCBs, and dioxins in food animals, their public health implications.
AB  - Polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), and dioxins
      are shown to have toxic potential in food animals and humans through laboratory
      research and investigation of accidental exposures. This article discusses the
      ball clay incident, as well as other examples of known accidental exposures to
      PBBs and PCBs. Background information regarding the mechanism of toxicity and
      effects in animals and humans is also included.

PMID- 10088216
TI  - Mycotoxicosis in food producing animals.
AB  - Mycotoxins are toxic secondary metabolites of fungi. Diseases caused by
      mycotoxins are collectively referred to as mycotoxicosis. Disease is usually
      initiated after ingestion of feeds containing toxic doses of mycotoxins. Signs
      and symptoms vary and depend on the animal, the organ system involved, and on the
      dose and type of mycotoxins ingested. The symptoms can range from acute death,
      immunosuppression to skin lesions or to signs of hepatotoxicity, nephrotoxicity,
      neurotoxicity, or genotoxicity. In addition to concerns over adverse effects of
      mycotoxins on food animals consuming mycotoxin-contaminated feeds, there is also
      a public health concern over the potential for human beings to consume animal
      derived food products such as meat, milk, or eggs, containing residues of those
      mycotoxins or their metabolites.

PMID- 10088217
TI  - Center for Veterinary Medicine's perspective on the beef hormone case.
AB  - Steroidal sex hormones and synthetic derivatives are used in the US to enhance
      growth in food-producing animals. The European Economic Community has banned use
      of these same substances, reportedly on the grounds of food safety. The US
      maintains that this ban was and is a disguised restriction on trade. The
      technical grounds for bringing this case and the impact of the findings of the
      World Trade Organization on the regulation of animal drugs in the US is
      discussed.

PMID- 10088218
TI  - International harmonization issues.
AB  - With the globalization of trade in many product sectors occurring at a rapid
      pace, interest in international harmonization issues relating to veterinary
      products continues to grow. Because of the potential impact on trade, there has
      been a focus for several years on harmonization of maximum residue limits (MRLs)
      or tolerances on a global basis. There has also been interest, especially on the
      part of pharmaceutical companies, to facilitate the approval of a veterinary
      product in multiple countries. This article discusses two major international
      initiatives that have been formed to address these harmonization areas of concern
      for veterinary products.

PMID- 10088219
TI  - Producer quality assurance programs.
AB  - Essentially all animal commodity organizations have established quality assurance
      programs designed to ensure food safety and quality. Most of these programs were
      originally implemented to address problems with veterinary drug residues. Many of
      the current programs have or plan to include food safety critical control points
      with specific guidelines on how to control or reduce pathogen load. The continued
      focus placed on food safety by today's consumer demands that American producers
      ensure that their commodities are wholesome, safe, and of high quality in order
      to remain competitive in the global marketplace. Veterinarians should recognize
      that it is important to encourage food animal producers to participate in quality
      assurance programs for their clients' economic health and for food safety and
      protection of public health. Commodities certified as being produced under good
      production practices or by producers certified as following a recognized and
      validated quality assurance program often bring a premium price. Also, some
      slaughter establishments are beginning to require producers to be certified as
      practicing under a recognized quality assurance program before animals are
      accepted for processing. This practice is being driven partially by the demands
      placed on slaughter establishments by the US Department of Agriculture's
      implementation of the Pathogen Reduction, Hazard Analysis and Critical Control
      Point Systems regulation. Regardless of why producer trade association quality
      assurance programs have come into existence, veterinarians should promote the
      programs as an excellent mechanism to help ensure everyone's goal of a safe,
      wholesome food supply.

PMID- 10088220
TI  - [Management of community-acquired lower respiratory infections. Definition,
      epidemiology, risk factors and prevention].

PMID- 10088221
TI  - [Management of community-acquired lower respiratory infections. Management in the
      hospital].

PMID- 10088222
TI  - [Biology of bronchial cancer. Molecular epidemiology].

PMID- 10088223
TI  - [Biology of bronchial cancer. Anomalies of the cellular cycle].

PMID- 10088224
TI  - [Bronchial cancer. Therapeutic modalities of the future. Angiogenesis and its
      applications].

PMID- 10088225
TI  - [Biology of bronchial cancer. Therapeutic modalities of the future. Apoptosis and
      gene therapy].

PMID- 10088226
TI  - [Particularities of smoking in adolescents].

PMID- 10088227
TI  - [Networks in oncology].

PMID- 10088228
TI  - [Program of medical information systems and resource allocation. How to
      optimize?].

PMID- 10088229
TI  - [Remodeling of the respiratory tract in asthma. Anatomo-pathology].

PMID- 10088230
TI  - [Remodeling of the respiratory tract in asthma. Biological factors and potential
      physiopathological implications in the apoptosis process].

PMID- 10088231
TI  - [Remodeling of the respiratory tract in asthma. Effects of treatment].

PMID- 10088232
TI  - [Results of a randomized multicenter study on nocturnal oxygen therapy in chronic
      obstructive lung disease not justifying conventional oxygen therapy].

PMID- 10088233
TI  - [Chronic obstructive lung disease in the agricultural milieu and in textile
      employees].

PMID- 10088234
TI  - [Chronic obstructive lung disease in the industrial milieu].

PMID- 10088235
TI  - [Medical-legal management in a suspected occupational chronic obstructive lung
      disease].

PMID- 10088236
TI  - [Medical-economic evaluation of bronchial cancer].

PMID- 10088237
TI  - [Bronchodilator nebulization in asthma and chronic obstructive lung disease.
      Practical modalities: choice of material, realization, maintenance].

PMID- 10088238
TI  - [Bronchodilator nebulization in bronchial obstructions].

PMID- 10088239
TI  - [Descriptive epidemiology: the numbers].

PMID- 10088240
TI  - [Analytic epidemiology: risk factors in France].

PMID- 10088241
TI  - [Epidemiology of precancerous lesions: from endoscopic detection to screening].

PMID- 10088242
TI  - [Difficult asthmas. Pitfalls and nosological limits].

PMID- 10088243
TI  - [Pleural pathology and nursing care].

PMID- 10088244
TI  - [Nursing care. Management of pain].

PMID- 10088245
TI  - [Computerized patient record: role of nursing care].

PMID- 10088246
TI  - [Virtual endoscopy: which indications?].

PMID- 10088247
TI  - [Quality of life measurement tools in respiratory pathology (excluding cancer)].

PMID- 10088248
TI  - [Role of angiographic scanning in the diagnostic strategy for pulmonary
      embolism].

PMID- 10088249
TI  - [Radon and bronchial cancer].

PMID- 10088250
TI  - [Transdermal administration: progress in the treatment of pain].

PMID- 10088251
TI  - [Systematic evaluation of hemostasis before a bronchoscopy--for].

PMID- 10088252
TI  - [Systematic evaluation of hemostasis before a bronchoscopy--against].

PMID- 10088253
TI  - [Prophylactic cerebral irradiation in localized small-cell carcinomas in complete
      remission--for].

PMID- 10088254
TI  - [Prophylactic cerebral irradiation in localized small-cell carcinomas in complete
      remission--against].

PMID- 10088255
TI  - [Early thoracoscopy in the diagnosis of serofibrinous, exudative pleurisies-
      for].

PMID- 10088256
TI  - [Early thoracoscopy in clear-exudate pleurisies--against].

PMID- 10088257
TI  - [Use of delayed-action beta-2 mimetics in the management of chronic obstructive
      bronchial diseases--for].

PMID- 10088258
TI  - [Use of delayed-action beta-2 mimetics in the management of chronic obstructive
      bronchial disease--against].

PMID- 10088259
TI  - [Diagnostic techniques for bronchial cancer. New scintigraphic techniques
      (immunoscintigraphy and positron-emission tomography)].

PMID- 10088260
TI  - [Role and limits of cytology in the diagnosis of bronchial cancer].

PMID- 10088261
TI  - [Imaging of normal and pathologic diaphragm].

PMID- 10088262
TI  - [Diagnostic and therapeutic management of a diaphragmatic paralysis].

PMID- 10088263
TI  - [Surgical treatment of chronic diaphragmatic paralysis and eventrations].

PMID- 10088264
TI  - [Functional sequelae from oncologic treatments in children].

PMID- 10088265
TI  - [Techniques and indications for bronchoscopy in the artificially ventilated
      patient].

PMID- 10088266
TI  - [Value of bronchoalveolar lavage in an artificially ventilated patient].

PMID- 10088267
TI  - [Systemic prolonged corticotherapy: prevention and treatment strategy for
      corticosteroid-induced osteoporosis].

PMID- 10088268
TI  - [Other complications and withdrawal modalities in systemic prolonged
      corticotherapy].

PMID- 10088269
TI  - [Role of expired nitric oxide measurement in respiratory function tests].

PMID- 10088270
TI  - [Possibilities opened by the negative expiratory pressure in respiratory function
      tests].

PMID- 10088271
TI  - [New techniques in the study of pulmonary circulation].

PMID- 10088272
TI  - [New anatomo-pathologic classification from W.H.O].

PMID- 10088273
TI  - [From dysplasia to cancer: cytologic, histopathologic and molecular aspects].

PMID- 10088274
TI  - [Should we improve the TMN 1997 classification?].

PMID- 10088275
TI  - [Practical management of non-invasive ventilation in acute respiratory
      insufficiency and chronic obstructive respiratory insufficiency].

PMID- 10088276
TI  - [Role and managmement of non-invasive ventilation in respiratory distress in the
      obese subject].

PMID- 10088277
TI  - [Physiopathology of coughing].

PMID- 10088278
TI  - [Little known causes of cough].

PMID- 10088279
TI  - [Which initial evaluation for non-small-cell bronchial cancers?].

PMID- 10088280
TI  - [Management of non-small-cell bronchial cancers. Combined therapy, radio
      chemotherapy].

PMID- 10088281
TI  - [Management of non-small-cell bronchial cancers. Which chemotherapy for a stage
      IV?].

PMID- 10088282
TI  - [Management of non-small-cell bronchial cancers. Preoperative treatment].

PMID- 10088283
TI  - [Management of non-small-cell bronchial cancers. Postoperative adjuvant
      treatments].

PMID- 10088284
TI  - [Management of non-small-cell bronchial cancers. Which postoperative follow-up,
      which complementary examinations, at what frequency?].

PMID- 10088285
TI  - [Cystic fibrosis. Passage from pediatric management to adult medicine
      management].

PMID- 10088286
TI  - [Cystic fibrosis. Current indications for nebulized treatments: antibiotics and
      DNase].

PMID- 10088287
TI  - [Cystic fibrosis. Non-invasive ventilation: indications and results].

PMID- 10088288
TI  - [Cystic fibrosis. Extra-respiratory manifestations].

PMID- 10088289
TI  - [Diagnostic kinesitherapy tools in pneumology].

PMID- 10088290
TI  - [Kinesitherapy and asthma: current trends].

PMID- 10088291
TI  - [Rehabilitation of severely hypoxemic patients with chronic obstructive lung
      disease].

PMID- 10088292
TI  - [Hygiene and disinfection best practices for home assisted respiratory care].

PMID- 10088293
TI  - [Kinesitherapy management of bronchiolitis].

PMID- 10088294
TI  - [Oxygen therapy in children].

PMID- 10088295
TI  - [Which initial evaluation for small-cell bronchial cancers?].

PMID- 10088296
TI  - [Limited forms of treatment for small-cell cancers].

PMID- 10088297
TI  - [Which chemotherapy for diffuse forms of small-cell cancers?].

PMID- 10088298
TI  - [Update on transthoracic biopsy].

PMID- 10088299
TI  - [Superior vena cava endoprostheses].

PMID- 10088300
TI  - [Functional, pediatric respiratory tests. Which tests to propose and at what
      age?].

PMID- 10088301
TI  - [Resistance measurement by the interruption technique of flow].

PMID- 10088302
TI  - [Measurement of resistance by the forced oscillation technique].

PMID- 10088303
TI  - [Follow-up of pleural benign pathologies].

PMID- 10088304
TI  - [Pertussis: a current disease. Epidemiology and physiopathology].

PMID- 10088305
TI  - [Pertussis: a current disease. New diagnostic techniques].

PMID- 10088306
TI  - [Which criteria of quality in oncologic thoracic surgery?].

PMID- 10088307
TI  - [Extended surgery of lung cancer].

PMID- 10088308
TI  - [Video-surgery of pulmonary cancer].

PMID- 10088309
TI  - [Relative importance of domestic pollution and atmospheric pollution on
      respiratory health].

PMID- 10088310
TI  - [Pollution and asthma].

PMID- 10088311
TI  - [Pollution and bronchial cancer].

PMID- 10088312
TI  - [Home management of chronic respiratory insufficiency. Non-invasive ventilation
      at home].

PMID- 10088313
TI  - [Home management of chronic respiratory insufficiency. Oxygen inhalation
      therapy].

PMID- 10088314
TI  - [Mesothelioma surgery].

PMID- 10088315
TI  - [Surgery for bronchial dilatation].

PMID- 10088316
TI  - [Indications and limits of pulmonary volume reduction surgery].

PMID- 10088317
TI  - [Information and disinformation. Repercussions on serious public health
      problems].

PMID- 10088318
TI  - [Accessibility of nicotine substitution products and prevention of cancers].

PMID- 10088319
TI  - [Health personnel stress facing cancer and cancer patients].

PMID- 10088320
TI  - [Palliative care: from an ethic of conviction to a beginning discussion].

PMID- 10088321
TI  - [Thinking about death inside a hospital institution].

PMID- 10088322
TI  - [The air that we breathe].

PMID- 10088323
TI  - [Pulmonary auscultation and kinesitherapy in pediatrics].

PMID- 10088324
TI  - [Campylobacter enteritis].

PMID- 10088325
TI  - [Legionellosis (Legionnaires' disease, Pontiac fever)].

PMID- 10088326
TI  - [Toxic shock syndrome (TSS)].

PMID- 10088327
TI  - [E.coli O157 infection].

PMID- 10088328
TI  - [Pseudomembranous colitis (Clostridium difficile infection)].

PMID- 10088329
TI  - [Helicobacter pylori].

PMID- 10088330
TI  - [Vibrio cholerae O139 (Bengal) infection].

PMID- 10088331
TI  - [Rotavirus infection].

PMID- 10088332
TI  - [Adult T-cell leukemia].

PMID- 10088333
TI  - [Acquired immunodeficiency syndrome (AIDS)].

PMID- 10088334
TI  - [HHV-6 infection, HHV-7 infection].

PMID- 10088335
TI  - [HHV8 infection (Kaposi's sarcoma)].

PMID- 10088336
TI  - [Hepatitis C virus infection].

PMID- 10088337
TI  - [Hepatitis D].

PMID- 10088338
TI  - [Hepatitis E].

PMID- 10088339
TI  - [Hepatitis G].

PMID- 10088340
TI  - [TTV hepatitis].

PMID- 10088341
TI  - [Borna disease virus infection].

PMID- 10088342
TI  - [Clinical features of the new influenza virus infection].

PMID- 10088343
TI  - [Lassa fever: its virological and clinical aspects].

PMID- 10088344
TI  - [Ebola hemorrhagic fever and Marburg virus disease: their virological and
      clinical aspects].

PMID- 10088345
TI  - [Hantavirus infection].

PMID- 10088346
TI  - [Crimean-Congo hemorrhagic fever].

PMID- 10088347
TI  - [Cryptosporidium, Cyclospora, Microsporidia].

PMID- 10088348
TI  - [Lyme disease].

PMID- 10088349
TI  - [Ehrlichiosis].

PMID- 10088350
TI  - [Cat scratch disease].

PMID- 10088351
TI  - [Streptococcal toxic shock-like syndrome].

PMID- 10088352
TI  - [Plague].

PMID- 10088353
TI  - [Diphtheria].

PMID- 10088354
TI  - [Tuberculosis].

PMID- 10088355
TI  - [Pertussis].

PMID- 10088356
TI  - [Salmonellosis].

PMID- 10088357
TI  - [Cholera].

PMID- 10088358
TI  - [Rabies].

PMID- 10088359
TI  - [Dengue fever: its virological and clinical aspects].

PMID- 10088360
TI  - [Yellow fever].

PMID- 10088361
TI  - [Malaria].

PMID- 10088362
TI  - [Schistosomiasis].

PMID- 10088363
TI  - [Leishmaniasis].

PMID- 10088364
TI  - [Toxoplasmosis].

PMID- 10088365
TI  - [Echinococcosis].

PMID- 10088366
TI  - [Penicillin resistant Streptococcus pneumoniae infection].

PMID- 10088367
TI  - [Methicillin resistant Staphylococcus aureus infection].

PMID- 10088368
TI  - [Infections of vancomycin resistant enterococci (VRE) and Staphylococcus aureus
      (VRSA)].

PMID- 10088369
TI  - [Extended-spectrum beta-lactamase producing gram negative rods infection].

PMID- 10088370
TI  - [Metallo-beta-lactamase producing gram negative rods infection].

PMID- 10088371
TI  - [Multidrug-resistant tuberculosis].

PMID- 10088372
TI  - [Multi-drug resistant mycobacterial infection].

PMID- 10088373
TI  - [Multi-drug resistant Pseudomonas aeruginosa infection].

PMID- 10088374
TI  - [Multidrug resistant mycosis].

PMID- 10088375
TI  - [Drug resistant malaria].

PMID- 10088376
TI  - [Subacute spongiform encephalopathy].

PMID- 10088377
TI  - [Creutzfeldt-Jakob disease].

PMID- 10088378
TI  - [Gerstmann-Straussler-Scheinker syndrome].

PMID- 10088379
TI  - [Kuru].

PMID- 10088380
TI  - [Fatal familial insomnia].

PMID- 10088381
TI  - [Iatrogenic prion disease].

PMID- 10088382
TI  - [Toxic shock-like syndrome].

PMID- 10088383
TI  - [Systemic inflammatory response syndrome (SIRS)].

PMID- 10088384
TI  - [Staphylococcal sepsis].

PMID- 10088385
TI  - [Septic shock].

PMID- 10088386
TI  - [Yersinia enterocolitica septicemia].

PMID- 10088387
TI  - [Melioidosis].

PMID- 10088388
TI  - [Sepsis by Escherichia coli].

PMID- 10088389
TI  - [Klebsiella sepsis].

PMID- 10088390
TI  - [Sepsis by Pseudomonas aeruginosa].

PMID- 10088391
TI  - [Aeromonas septicemia].

PMID- 10088392
TI  - [Whipple's disease].

PMID- 10088393
TI  - [Infectious encephalitis].

PMID- 10088394
TI  - [Postinfectious encephalomyelitis].

PMID- 10088395
TI  - [Meningococcal meningitis].

PMID- 10088396
TI  - [Pneumococcal meningitis].

PMID- 10088397
TI  - [Staphylococcus meningitis].

PMID- 10088398
TI  - [Listeria meningitis].

PMID- 10088399
TI  - [Haemophilus influenzae meningitis].

PMID- 10088400
TI  - [Campylobacter meningitis].

PMID- 10088401
TI  - [Brain abscess].

PMID- 10088402
TI  - [Cerebral venous (sinus) thrombosis].

PMID- 10088403
TI  - [General paresis].

PMID- 10088404
TI  - [Tabes dorsalis].

PMID- 10088405
TI  - [Purulent pericarditis].

PMID- 10088406
TI  - [Bacterial myocarditis].

PMID- 10088407
TI  - [Infective endocarditis].

PMID- 10088408
TI  - [Mycotic aneurysm and mycotic aortitis].

PMID- 10088409
TI  - [Pericardial abscess].

PMID- 10088410
TI  - [Pneumococcal pneumonia].

PMID- 10088411
TI  - [Staphylococcal pneumonia].

PMID- 10088412
TI  - [Streptococcal pneumonia].

PMID- 10088413
TI  - [Listeriosis].

PMID- 10088414
TI  - [Inhalation anthrax].

PMID- 10088415
TI  - [Bacillus cereus pneumonia].

PMID- 10088416
TI  - [Branhamella pneumonia].

PMID- 10088417
TI  - [Klebsiella pneumoniae pneumonia].

PMID- 10088418
TI  - [Pseudomonas aeruginosa pneumonia].

PMID- 10088419
TI  - [Escherichia coli pneumonia].

PMID- 10088420
TI  - [Haemophilus influenzae pneumonia].

PMID- 10088421
TI  - [Serratia marcescens pneumonia].

PMID- 10088422
TI  - [Pasteurella multocida pneumonia].

PMID- 10088423
TI  - [Francisella pneumonia].

PMID- 10088424
TI  - [Xanthomonas maltophilia pneumonia].

PMID- 10088425
TI  - [Anaerobic pneumonia].

PMID- 10088426
TI  - [Pulmonary actinomycosis, pulmonary nocardiosis].

PMID- 10088427
TI  - [Community-acquired pneumonia].

PMID- 10088428
TI  - [Hospital-acquired pneumonia].

PMID- 10088429
TI  - [Acute upper airway infection].

PMID- 10088430
TI  - [Acute tonsillitis].

PMID- 10088431
TI  - [Peritonsillar space infections--peritonsillar abscess].

PMID- 10088432
TI  - [Acute bronchitis].

PMID- 10088433
TI  - [Chronic bronchitis].

PMID- 10088434
TI  - [Diffuse panbronchiolitis (DPB)].

PMID- 10088435
TI  - [Bacterial pleurisy].

PMID- 10088436
TI  - [Lung abscess].

PMID- 10088437
TI  - [Cholangitis and cholecystitis].

PMID- 10088438
TI  - [Pericholecystic abscess].

PMID- 10088439
TI  - [Liver abscess].

PMID- 10088440
TI  - [Hepatic listeriosis].

PMID- 10088441
TI  - [Hepatic actinomycosis].

PMID- 10088442
TI  - [Methicillin-cephem-resistant Staphylococcus aureus enteritis].

PMID- 10088443
TI  - [Food-borne botulism].

PMID- 10088444
TI  - [Staphylococcal food poisoning].

PMID- 10088445
TI  - [Bacillus cereus food poisoning].

PMID- 10088446
TI  - [Staphylococcal enterocolitis].

PMID- 10088447
TI  - [Clostridium perfringens food poisoning].

PMID- 10088448
TI  - [Bacillary dysentery, ekiri].

PMID- 10088449
TI  - [Bacterial esophagitis].

PMID- 10088450
TI  - [Acute purulent gastritis].

PMID- 10088451
TI  - [Acute appendicitis].

PMID- 10088452
TI  - [Typhoid fever--paratyphoid fever].

PMID- 10088453
TI  - [Vibrio parahaemolyticus enteritis].

PMID- 10088454
TI  - [Yersinia enteritis].

PMID- 10088455
TI  - [Yersinia pseudotuberculosis infection].

PMID- 10088456
TI  - [Actinomycosis of the esophagus].

PMID- 10088457
TI  - [Actinomycosis of the intestine].

PMID- 10088458
TI  - [Acute pancreatitis].

PMID- 10088459
TI  - [Pancreatic abscess].

PMID- 10088460
TI  - [Acute-chronic pyelonephritis].

PMID- 10088461
TI  - [Emphysematous pyelonephritis].

PMID- 10088462
TI  - [Acute cystitis].

PMID- 10088463
TI  - [Chronic cystitis].

PMID- 10088464
TI  - [Urethritis].

PMID- 10088465
TI  - [Prostatitis syndrome].

PMID- 10088466
TI  - [Acute post-streptococcal glomerulonephritis].

PMID- 10088467
TI  - [HUS caused by enterohemorrhagic E. coli].

PMID- 10088468
TI  - [Tubulointerstitial nephritis induced by chronic bacterial infection].

PMID- 10088469
TI  - [Specific infections of the kidney].

PMID- 10088470
TI  - [Impetigo contagiosa (staphylococcal, streptococcal].

PMID- 10088471
TI  - [Staphylococcal scalded skin syndrome].

PMID- 10088472
TI  - [Impetigo bockhart].

PMID- 10088473
TI  - [Folliculitis].

PMID- 10088474
TI  - [Carbuncle].

PMID- 10088475
TI  - [Phlegmon (cellulitis)].

PMID- 10088476
TI  - [Ecthyma vulgare, ecthyma gangrenosum, chancriform pyoderma].

PMID- 10088477
TI  - [Abscess of the apocrine sweat glands].

PMID- 10088478
TI  - [Clostridial gas gangrene].

PMID- 10088479
TI  - [Non-clostridial gas gangrene].

PMID- 10088480
TI  - [Pyomyositis].

PMID- 10088482
TI  - [Acute superficial lymphangitis].

PMID- 10088481
TI  - [Clostridial myonecrosis].

PMID- 10088483
TI  - [Osteomyelitis].

PMID- 10088484
TI  - [Suppurative arthritis].

PMID- 10088485
TI  - [Anthrax].

PMID- 10088486
TI  - [Tetanus].

PMID- 10088487
TI  - [Brucellosis].

PMID- 10088488
TI  - [Cervical lymphadenitis].

PMID- 10088489
TI  - [Acute suppurative thyroiditis].

PMID- 10088490
TI  - [Pelvic peritonitis].

PMID- 10088491
TI  - [Intraabdominal abscess].

PMID- 10088492
TI  - [Periproctal abscess].

PMID- 10088493
TI  - [Bartonellosis].

PMID- 10088494
TI  - Characteristics of cartilage engineered from human pediatric auricular cartilage.
AB  - In the repair of cartilage defects, autologous tissue offers the advantage of
      lasting biocompatibility. The ability of bovine chondrocytes isolated from
      hyaline cartilage to generate tissue-engineered cartilage in a predetermined
      shape, such as a human ear, has been demonstrated; however, the potential of
      chondrocytes isolated from human elastic cartilage remains unknown. In this
      study, the authors examined the multiplication characteristics of human auricular
      chondrocytes and the ability of these cells to generate new elastic cartilage as
      a function of the length of time they are maintained in vitro. Human auricular
      cartilage, harvested from patients 5 to 17 years of age, was digested in
      collagenase, and the chondrocytes were isolated and cultured in vitro for up to
      12 weeks. Cells were trypsinized, counted, and passaged every 2 weeks.
      Chondrocyte-polymer (polyglycolic acid) constructs were created at each passage
      and then implanted into athymic mice for 8 weeks. The ability of the cells to
      multiply in vitro and their ability to generate new cartilage as a function of
      the time they had been maintained in vitro were studied. A total of 31
      experimental constructs from 12 patients were implanted and compared with a
      control group of constructs without chondrocytes. In parallel, a representative
      sample of cells was evaluated to determine the presence of collagen. The doubling
      rate of human auricular chondrocytes in vitro remained constant within the
      population studied. New tissue developed in 22 of 31 experimental implants. This
      tissue demonstrated the physical characteristics of auricular cartilage on gross
      inspection. Histologically, specimens exhibited dense cellularity and lacunae
      containing cells embedded in a basophilic matrix. The specimens resembled
      immature cartilage and were partially devoid of the synthetic material of which
      the construct had been composed. Analyses for collagen, proteoglycans, and
      elastin were consistent with elastic cartilage. No cartilage was detected in the
      control implants. Human auricular chondrocytes multiply well in vitro and possess
      the ability to form new cartilage when seeded onto a three-dimensional scaffold.
      These growth characteristics might some day enable chondrocytes isolated from a
      small auricular biopsy to be expanded in vitro to generate a large, custom
      shaped, autologous graft for clinical reconstruction of a cartilage defect, such
      as for congenital microtia.

PMID- 10088495
TI  - Reconstruction of a three-dimensional structure using cartilage regenerated from
      the perichondrium of rabbits.
AB  - Human tissues such as those found in the ear, nose, eyelid, lip, and larynx have
      complicated and delicate three-dimensional structures, which are difficult to
      reconstruct and restore to normal function following damage by tumor, congenital
      disease, or trauma. We devised a new reconstructive technique for the lost
      tissues by using cartilage regenerated from the perichondrium. In 12 ears of 12
      rabbits, the layer between the perichondrium and the cartilage was stripped off.
      The exposed cartilage was punched out in large amounts to resemble a flexible,
      honeycomb-like structure. Then, we sandwiched the rabbit ears with two
      thermoplastic plates, which maintained a structure of the anterior surface of the
      human ear for 8 weeks. Structural change was studied in all cases, and some parts
      of the remodeled tissue were studied pathologically. Out of 12 ears, 8 had a
      rigid structure with a shape like a human ear using regenerated cartilage from
      the perichondrium of rabbits, 2 were infected, and 2 had a decubitus ulcer on the
      conchal surface as a result of compression from the plate. This study suggests
      that the use of the cartilage regenerated from the perichondrium may lead to a
      successful treatment also in humans for a variety of three-dimensional structures
      that have been damaged.

PMID- 10088496
TI  - Primary and secondary orbit surgery: the transconjunctival approach.
AB  - The transconjunctival approach to the orbit is underutilized because of concern
      regarding inadequate exposure and higher postoperative rates of lower eyelid
      shortening and ectropion. All patients who had a transconjunctival incision
      performed for orbital surgery over the last 6 years (1990 to 1996) were studied.
      Patients who had a transconjunctival blepharoplasty were excluded. A total of 35
      patients, average age 32 years, had 45 transconjunctival incisions performed.
      Lateral canthotomy or cantholysis was not done. Operations fell into three
      categories: fracture plating alone, 10 (22 percent); split-calvarial bone graft
      placement with or without plating, 26 (58 percent); and orbital decompression, 9
      (20 percent). The overall incidence of ectropion was 6.7 percent (3 of 45). One
      patient (2 percent) had transient ectropion, and two patients (4 percent) had
      persistent ectropion, which required surgical correction. Ectropion occurred only
      in those lower eyelids that had a previous transcutaneous incision (3 of 18 = 17
      percent). None occurred in those eyelids that had no prior incision or only a
      previous transconjunctival incision. The transconjunctival approach without a
      lateral canthotomy provides safe access to the orbit in eyelids that have not had
      a previous transconjunctival incision.

PMID- 10088497
TI  - Surgical reconstruction of the contracted orbit.
AB  - Anophthalmic patients and patients afflicted with retinoblastoma incur severe
      deformity of the orbit. Treatment of the severely contracted orbit is very
      difficult, and patient satisfaction is often poor. Since 1988, we have performed
      temporalis muscle transfer and surgical expansion of the contracted bony orbit in
      26 patients. Satisfactory results were obtained. Gradual expansion of the orbit
      was performed in case of congenital anophthalmic patients. The treatment should
      be established in multiplicity, among many methods available for contracted eye
      sockets, according to the degree of orbital deformity and the amount of residual
      conjunctiva. In case of severe deformity, volume expansion surgery and temporalis
      muscle transfer are necessary. If augmentation is required in the periorbital
      region, rib bone onlay graft must be performed. We were able to shorten the
      operative time by modifying the three-wall orbital expansion technique of Tessier
      and Wolfe to a more simplified method. Our observations show that our procedures
      achieved symmetry in both eyes in all patients, and there have been no remarkable
      complications.

PMID- 10088498
TI  - Outcome of scalp donor sites in 450 consecutive pediatric burn patients.
AB  - The scalp is a useful and reliable donor site in pediatric burn patients that can
      be multiply harvested with minimal morbidity. Healing complications, however, may
      include alopecia and chronic folliculitis. To investigate scalp donor-site
      morbidity, a consecutive series of 2478 pediatric burn patients treated over a 10
      year period were reviewed. A total of 450 of these patients had scalp donor sites
      for wound closure. Percent of total body surface area burned was 46+/-23 percent
      (mean+/-standard deviation), and the mean number of sequential scalp donor-site
      harvests was 2.2+/-2 (range, 1 to 10) with mean intervals between harvesting of
      6+/-0.6 days. Ten patients (2.2 percent) had related complications. Eight
      patients developed scalp folliculitis, with Staphylococcus sp as the predominant
      organism (80 percent). Two patients were managed successfully with wound care
      alone; the other six patients required surgical debridement and split-thickness
      skin grafting to achieve wound healing. These eight patients developed varying
      degrees of alopecia. Two patients developed alopecia without previous
      folliculitis. Six patients required reconstructive surgery, which consisted of
      primary closure (3), staged excision (1), and tissue expansion (2). A number of
      variables were examined to determine any differences in the group that had
      complications compared with the group of patients that did not. No differences in
      age, sex, race, burn type, burn size, septic episodes, time to wound closure, or
      number of times the scalp was harvested were detected. Healed second-degree burns
      to the scalp that were subsequently taken as donor sites seemed to be a risk
      factor (p < 0.05) for folliculitis and alopecia. Our study confirms that scalp
      donor sites are reliable with low morbidity. Complications include alopecia and
      chronic folliculitis that can be avoided by meticulous technique and avoidance of
      previously burned areas.

PMID- 10088499
TI  - Prevention and treatment of wide scar and alopecia in the scalp: wedge excision
      and double relaxation suture.
AB  - The visible linear scar of the scalp is a cosmetically serious complication of a
      scalp incision in scalp surgery, forehead lift, and craniofacial surgery,
      especially on the temporal scalp. Its causes are cicatrical alopecia and scar
      widening. To solve this problem, we performed the wedge excision of the scalp and
      the double relaxation suture of the galea in 2 patients undergoing facial surgery
      through the coronal approach and in 15 patients with scalp alopecia ranging from
      0.5 to 3.0 cm in width. The wedge excision using the beveling incision at an
      angle of 30 degrees to the hair follicles preserves the deep hair follicles of
      the flap margins and allows the hair to grow into the scar, eventually preventing
      cicatricial alopecia and camouflaging the linear scar. The double relaxation
      suture of the trimmed galea with nonabsorbable suture with or without the
      relaxation incision minimizes skin tension for a long time, eventually preventing
      scar widening. This procedure was followed by the superficial skin suture for
      maintaining the skin sutures for a long time and avoiding the injury of the
      superficial hair follicles. In all patients, we observed an excellent cosmetic
      result of unnoticed scar line without complications during the follow-up period
      of 10 weeks to 6 months.

PMID- 10088500
TI  - The MCFONTZL classification system for soft-tissue injuries to the face.
AB  - A review of the literature and case records reflected a need for the development
      of a clinically applicable assessment scheme and classification system for soft
      tissue laceration injuries to the face. Herein, a systematic approach for
      assessing facial lacerations is proposed based on location, depth of penetration,
      branching, directionality, size, presence of soft-tissue defect, and translation
      of such injuries into the current procedural terminology (CPT) code. Moreover, a
      new classification system for facial laceration injuries is presented that may
      serve as the basis for simplification of current billing codes. Prospective
      clinical application of this classification system may lead to standardization of
      facial injury assessment and improvement in the incomplete and inconsistent
      patient record. This system will establish a reliable database that may identify
      factors in soft-tissue injuries that contribute to poor aesthetic results or
      secondary functional deformities. These data will lead to the modification of
      established treatment plans.

PMID- 10088501
TI  - Management of secondary soft-tissue deficits following microsurgical head and
      neck reconstruction by means of another free flap.
AB  - Secondary soft-tissue deficits may develop following a microsurgical
      reconstruction in the head and neck region because of inadequate planning or
      chronic effects of radiotherapy. Although most cases could be managed with
      alternative methods, free flaps might be necessary in difficult cases. Herein are
      described 11 cases of microsurgical head and neck reconstruction in which
      secondary soft-tissue deficits required transfer of another soft-tissue free
      flap. All patients had malignant tumors treated with surgical resection, and
      their defects were reconstructed with free flaps. Seven patients received either
      preoperative or postoperative adjunctive radiotherapy. These patients gradually
      developed signs and symptoms of soft-tissue deficiency in the reconstructed area,
      and a soft-tissue free flap transfer was required for treatment within an average
      of 21.5 months of their initial reconstruction. Five rectus abdominis, one rectus
      femoris, one latissimus dorsi, one tensor fasciae latae myocutaneous, one radial
      forearm, one medial arm, and one dorsalis pedis flap were used for this purpose.
      All flaps survived completely. The average follow-up time was 32 months.
      Significant improvement was achieved in all cases, and no further major surgical
      procedures were required. Secondary soft-tissue deficits that could not be
      predicted or prevented during the initial microsurgical reconstruction may be
      treated successfully by a subsequent free soft-tissue transfer in selected cases.

PMID- 10088502
TI  - Barium swallows after free jejunal transfer: should they be performed routinely?
AB  - Fistula formation after free jejunal transfer for pharyngoesophageal
      reconstruction is a serious complication with potentially critical consequences.
      Barium swallow is used postoperatively to check for anastomotic competence before
      feeding but has been unreliable as a predictor of leak at our institution. The
      objective of this study was to evaluate the role of routine postoperative barium
      swallow in 41 consecutive jejunal transfers. Thirty-nine patients who underwent
      41 consecutive free jejunal transfers had a routine barium swallow performed
      between postoperative days 12 and 17. Radiologic findings and clinical outcome
      were evaluated and correlated. All barium swallows were reviewed by a single
      experienced radiologist in a blinded fashion. One total and one partial flap
      failure necessitated a second free jejunal transfer. Pharyngocutaneous fistulae
      developed after nine free jejunal transfers, of which the barium swallow was
      normal in four (44 percent) and showed a leak in five (56 percent). In the 32
      free jejunal transfers with no clinical leaks, 6 (19 percent) had radiologic
      leakage of contrast. Thus, barium swallow was normal in 30 patients and showed
      leakage in 11 patients. Normal barium swallow correlated with uncomplicated
      clinical course in 26 of 30 cases. In the remaining four cases (13 percent),
      however, a delayed fistula developed, which was secondary to flap necrosis in one
      case (negative predictive value 87 percent). On the other hand, radiologic leaks
      corroborated clinical fistula in 5 of 11 cases (45 percent), whereas no fistula
      developed in 6 cases (positive predictive value 46 percent). Of the five patients
      with clinical fistulae, four had early leaks (within 1 week), and the barium
      swallow did not provide additional information. The fifth patient developed a
      delayed leak 2 weeks after the barium swallow. Review of these barium swallows at
      the time of this study reversed the initial report of leakage in three patients,
      improving the predictive value to 63 percent. These patients had an uncomplicated
      clinical course. The positive predictive value of clinical assessment alone was
      63 percent. We conclude that barium studies following free jejunal transfers can
      be difficult to interpret, but an experienced radiologist can improve their
      accuracy. A normal barium swallow, however, does not ensure an uneventful
      clinical course. Similarly, radiologic leaks do not imply a clinical complication
      of fistula. Clinical judgment should therefore be exercised in initiating oral
      intake after free jejunal transfer. Barium swallow should be used only as an
      adjunct to aid in patient management.

PMID- 10088503
TI  - Bakamjian island flap for patch esophagoplasty of the cervical esophagus.
AB  - Esophageal stricture may result from chemical injury, progressive ischemic
      fibrosis, constriction of a previous esophagocolonic anastomosis site, or
      vascular insufficiency of the transferred gut. The Bakamjian skin island flap was
      employed as a patch for esophagoplasty to relieve focal esophageal stricture in
      12 patients. One of these patients developed postoperative leakage, which
      necessitated a secondary revision. The others had a smooth postoperative course
      and were able to resume oral intake with ease. It is concluded that the Bakamjian
      skin island flap is a reliable and convenient method for repairing short defects
      of the cervical esophagus in one stage.

PMID- 10088504
TI  - The blood supply of the reverse temporalis muscle flap: anatomic study and
      clinical implications.
AB  - Although the reverse temporalis muscle flap has been used clinically, the exact
      vascular connection between the superficial and deep temporal vessels has not
      been clearly defined. The purpose of this study was to investigate the vascular
      territory of the reverse temporalis muscle supplied by the superficial temporal
      vessels. Six cadaver heads were studied using a colored lead oxide injection
      through the superficial temporal artery. The specimens were examined
      macroscopically and radiographically. The reverse temporalis muscle flap was then
      applied to a clinical case presenting with traumatic anterior skull base defect
      communicating with the nasal cavity. The cadaver specimens demonstrated that the
      superficial temporal artery formed an average 1.3 +/- 0.2 cm in width of dense
      vascular zone, which was located within 1.8 cm below the superior temporal line.
      The dense vascular network further perfused the anterior and posterior deep
      temporal arteries and the muscular branch of the middle temporal artery to supply
      the temporalis muscle. The mean perfused area of the temporalis muscle was 83
      percent, ranging from 79 to 89 percent, in five cadaver heads. One cadaver
      revealed only 55 percent of perfused area in the absence of the muscular branch
      of the middle temporal artery. The consistent area without perfusion was located
      in the distal third of the posterior portion of the reverse temporalis muscle. In
      clinical cases, the reverse temporalis muscle flap was used successfully to
      obliterate the anterior skull base defect without evidence of muscle flap
      necrosis. The exact blood supply to the distal third of the posterior portion of
      the reverse temporalis muscle flap needs to be investigated further in vivo.
      Particular attention was paid to the inclusion of the muscular branch of the
      middle temporal artery in this flap to augment the blood supply to the temporalis
      muscle.

PMID- 10088505
TI  - The sternalis muscle: a normal finding encountered during breast surgery.
AB  - We report a case of mastectomy and immediate reconstruction in which the
      sternalis muscle, a normal anatomic variant, was encountered. Most surgeons we
      surveyed are not familiar with this variant.

PMID- 10088506
TI  - Anterolateral thigh flap for abdominal wall reconstruction.
AB  - The free or pedicled anterolateral thigh flap was introduced for the
      reconstruction of large abdominal wall defects. This flap is superior to the
      tensor fasciae latae musculocutaneous flap in several respects. These include the
      wide, reliable skin territory (which can reach the level of the knee) and the
      long pedicle. Therefore, a pedicled anterolateral thigh flap with reliable blood
      circulation can easily be positioned above the umbilicus. In addition, the free
      anterolateral thigh flap has greater freedom of orientation and can be used to
      repair larger abdominal wall defects than can the tensor fasciae latae flap.
      Seven patients in whom abdominal wall defects had been reconstructed with
      pedicled or free anterolateral thigh flaps were reviewed. Their average age was
      47.1 years (range, 21 to 74 years), and the average follow-up period was 10.7
      months (range, 2 to 21 months). The size of the abdominal wall defects ranged
      from 12 x 12 cm to 18 x 24 cm, and the size of the transferred flap ranged from
      10 x 20 cm to 20 x 20 cm. Three flaps were pedicled and four were free, of which
      three incorporated the tensor fasciae latae flap. All flaps survived completely,
      and no postoperative abdominal hernias developed. Despite some variations in
      vascular anatomy and technical difficulties in elevating the anterolateral thigh
      flap, the authors conclude that the pedicled or free anterolateral thigh flap is
      superior to the tensor fasciae latae flap for reconstruction of large abdominal
      wall defects.

PMID- 10088507
TI  - The use of skin grafts in postburn contracture release: a 10-year review.
AB  - Postburn scarring and contracture affecting function remain the most frustrating
      late complications of burn injury. Various techniques are used to release
      contractures; the choice depends on their location and/or the availability of
      unaffected skin adjacent to the contracture or elsewhere. A retrospective review
      was carried out of the case notes of patients who had skin grafting for the
      release of postburn contracture at the Burns Unit, City Hospital, Nottingham
      between May of 1984 and August of 1994 to evaluate the experience over this
      period. Information was obtained about the burn injury, contracture site,
      interval between burn and release of contracture, indication, age at first
      release, intervals between releases, operative details (donor and graft sites),
      complications and nonoperative treatment, and follow-up to the end of the study
      period. A total of 129 patients underwent skin grafting for release of
      contractures as opposed to any other method of correction. Full-thickness skin
      grafts were used in 81 patients (63 percent) and split-thickness skin grafts in
      26 (20 percent). Twenty-two patients (17 percent) had both types used on
      different occasions. Flame burns (41 percent) were the most common causes,
      followed by scalds (38 percent). Two hundred thirty-nine sites of contracture
      were released, with the axilla (59) and the hand/wrist (59) being the most common
      sites involved, followed by the head/neck region (42). It was found that for the
      same site, release with split-thickness skin grafts was associated with more
      rereleases of the contracture than with full-thickness skin grafts. Also, the
      interval between the initial release and first rerelease was shorter than with
      full-thickness skin grafts (p < 0.048). It was also noted that children required
      more procedures during growth spurts, reflecting the differential effect of the
      growth of normal skin and contracture tissue. Patients reported more satisfaction
      with texture and color match with the full-thickness skin grafts. There was
      comparable donor-site and graft morbidity with both graft types. The use of skin
      grafts is simple, reliable, and safe. Whenever possible, the authors recommend
      the use of full-thickness skin grafts in preference to split-thickness skin
      grafts in postburn contracture release.

PMID- 10088508
TI  - Bipedicle strap flaps in reconstruction of longitudinal dorsal skin defects of
      the digits.
AB  - Dorsal skin defects in which the loss of integument is longitudinal in shape are
      not uncommon after injury by rotating machinery and by glass shearing along the
      length of the digit. This shape of defect is difficult to reconstruct with
      commonly used flaps but lends itself to reconstruction by the use of longitudinal
      bipedicle strap flaps moved across the dorsum of the finger from lateral to
      medial. A variant of this traditional technique was used in the reconstruction of
      28 dorsal digital defects. The incidence of these defects and the need for this
      reconstructive technique were analyzed by a review of 1077 patients with dorsal
      digital injuries treated in a 6-year period between 1989 and 1995. Approximately
      20 percent of all dorsal digital injuries requiring flap reconstruction were
      suitable for reconstruction with bipedicle strap flaps.

PMID- 10088509
TI  - Salvage after severe lower-extremity trauma: are the outcomes worth the means?
AB  - Advances in reconstructive surgery have allowed for impressive salvage after
      severe lower-extremity trauma but not without complications when compared with
      immediate below-knee amputation. Several amputation index scores have been
      developed to help predict successful salvage as defined by a viable rather than a
      functional extremity. The purpose of this study was to evaluate retrospectively
      the predictive value of the amputation index scores and to assess prospectively
      overall health status and specific dysfunction in successful limb salvage and
      primary and secondary amputation by administering standardized generic and
      specific outcomes questionnaires (Medical Outcomes Study 36-Item Short-Form
      Health Survey, Western Ontario and MacMaster Universities Osteoarthritis Index).
      A retrospective chart review identified 55 severe lower-extremity injuries
      (Gustilo Type IIIB and IIIC) over a 12-year period (1984 to 1996). Forty-six
      severe open tibial fractures in 45 patients underwent attempted salvage. All
      required soft-tissue coverage by either local or free flap or vascular repair for
      leg salvage. The attempted-salvage group was subdivided into successful salvage
      and secondary amputation. The other nine patients underwent a primary amputation.
      There were no statistically significant differences in terms of patient
      demographics or other injuries (Injury Severity Score) in the three groups. Forty
      eight of 54 patients with an average 5-year follow-up completed a validated
      generic and specific outcomes health questionnaire. In the attempted-salvage
      group, 89 percent of patients had a successful salvage and 11 percent came to a
      secondary amputation. The amputation index scores correctly predicted an
      amputation in 32 percent of patients. The magnitude of the amputation index
      scores did not correlate with the physical outcomes scores and were not found to
      add any significant value of information to the surgeon's decision making.
      Patients undergoing primary and secondary amputation had a worse physical
      outcomes score (28 versus 38) than successful salvage (p < 0.007). Even so, the
      SF-36 (physical component score) outcomes score for this group of injured
      extremities, regardless as to whether salvaged or amputated, was as low as or
      lower than that of many serious medical illnesses, suggesting that severe lower
      extremity trauma impairs health as much as or more than being seriously ill. The
      mental component score in this group was comparable to that of a healthy
      population (49 versus 50), which implies the disability is primarily physical
      rather than psychological. Ninety-two percent of patients preferred their
      salvaged leg to an amputation at any stage of their injury, and none would have
      preferred a primary amputation.

PMID- 10088510
TI  - Spinal cord stimulation improves survival in ischemic skin flaps: an experimental
      study of the possible mediation by calcitonin gene-related peptide.
AB  - Currently, spinal cord stimulation is used to treat ischemia and ischemic pain,
      with the best results observed in vasospastic cases. It was earlier demonstrated
      that spinal cord stimulation may attenuate experimentally induced vasospasm in an
      island flap in the rat. The present study was designed to investigate whether
      preemptive spinal cord stimulation could increase long-term flap survival and to
      explore the neurohumoral mediation of the effect. A total of 56 rats were
      implanted with chronic spinal cord stimulation systems. Three days later, a groin
      flap based on the superficial epigastric vessels was harvested, and the single
      feeding artery was occluded by a detachable microvascular clip. After 12 hours,
      the clip was removed. Flap survival was evaluated after 7 days. Immediately
      before flap surgery, two groups of animals received 30 minutes of stimulation
      using current clinical parameters and with stimulation amplitudes of 70 (n = 10)
      or 90 percent (n = 8) of that evoking muscular contractions. The outcomes in
      these groups were compared with those in two control groups (n = 20; n = 10). In
      one group, an additional calcitonin gene-receptor peptide (CGRP) antagonist was
      intravenously injected before stimulation (n = 8). In the control groups without
      stimulation, virtually all flaps necrotized. In treated groups, flap survival was
      60 percent at the lower intensity and almost 90 percent at the higher one. The
      administration of a CGRP antagonist before treatment reduced its efficacy to
      below 40 percent survival. The differences between the untreated and treated
      groups were significant. The decrease in survival after CGRP-receptor block was
      significant in one of two tests. Preemptive spinal cord stimulation increases
      survival of skin flaps with critical ischemia. The effects are dependent on the
      stimulation intensity and are possibly mediated by the release of CGRP in the
      periphery.

PMID- 10088511
TI  - Bone neogenesis in domes made of expanded polytetrafluoroethylene: efficacy of
      rhBMP-2 to enhance the amount of achievable bone in rats.
AB  - For bone reconstructive purposes, it would be a great advantage to be able to
      gain bone without grafting. In experimental studies, barrier membranes have been
      used to accomplish this, however, with limited efficacy. In this study, the
      effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the early
      onset of bone formation, as well as on the final amount of achievable bone, was
      investigated in an experimental osteo-neogenesis model. In 60 adult rats, dome
      shaped barrier membranes made of expanded polytetrafluoroethylene (Gore-Tex
      membrane), with an inside volume of approximately 60 mm3, were placed on the left
      parietal bone. The domes were pretreated according to four different
      alternatives: (1) filled with autogenous blood only (n = 15); (2) filled with 5
      microg of rhBMP-2 in an absorbable collagen sponge carrier (n = 15); (3) filled
      with 15 microg of rhBMP-2 in absorbable collagen sponge carrier (n = 15); or (4)
      filled with the absorbable collagen sponge carrier only (n = 15). The animals
      treated according to each alternative were then divided into three equal groups
      with five rats in each, and subsequently killed after 3, 6, or 12 weeks. The
      amount of bone formed within the domes was evaluated by light microscopy and
      computer-assisted image analysis. It was found that the amount of newly formed
      bone could be enhanced by approximately 100 percent by simultaneous implantation
      of rhBMP-2, irrespective of dose. The early onset of bone formation was, however,
      not affected by the rhBMP-2 supplementation. This finding was interpreted as
      being due to the delivery system used, because as long as the carrier was still
      present, no significant difference between the treatment groups was observed. The
      bone formed in domes with carrier implantation, with or without rhBMP-2,
      displayed more marrow spaces in comparison to controls. The combined treatment
      with barrier membranes and local delivery of rhBMP-2 may be a useful tool in
      reconstructive surgery, for instance replacing onlay grafting, especially when a
      more delicate anatomy is necessary, because membranes can be shaped in multiple
      ways.

PMID- 10088512
TI  - Fibrodysplasia ossificans progressiva and associated osteochondroma of the
      coronoid process in a child.
AB  - The article reports the occurrence of osteochondroma in a fibrodysplasia
      ossificans progressiva patient. A 5-year-old boy presented with limited mouth
      opening and firm swelling of the right zygomatic complex area. The boy had
      bilateral hallux valgus of the great toes and heterotopic endochondral
      ossification of facial and neck regions. Associated osteochondroma of the
      coronoid process and aggressive heterotopic ossification of masticatory and neck
      muscles were found in response to traumatic injuries. Natural and clinical
      histories of fibrodysplasia ossificans progressiva were reviewed. An early
      diagnosis and avoidance of factors that aggravate ossification are key factors in
      reducing the expected degree of physical disabilities of patients. An early
      recognition of congenital skeletal deformities, early detection of abnormal
      ossification, and awareness of the disease by the involved physicians are
      important factors in the early diagnosis of the disease and in reducing any
      unnecessary trauma. Bone scintigrams and CT scans are effective noninvasive tools
      for an early detection of ossification and for monitoring the progression of the
      disease. Further investigation of its pathogenesis at a molecular level is
      important to understand better the nature of the disease and to develop an
      effective treatment protocol.

PMID- 10088513
TI  - Functional reconstruction after a total maxillectomy using a fibula
      osteocutaneous flap with osseointegrated implants.
AB  - The fibula osteocutaneous flap with osseointegrated implants was used for
      reconstruction of a total maxillectomy defect. We have achieved satisfactory
      reconstruction of three-dimensional facial structure, orbit support, and a
      functional prosthesis. Our procedure restored the patient's masticatory function
      of the maxilla and enabled good speech and a natural facial appearance. A very
      high quality of function was obtained without any complications, but long-term
      follow-up is necessary for maintenance of the implants.

PMID- 10088514
TI  - Treatment of late ulceration in free muscle flaps to the foot.
AB  - One of the preferred methods for the repair of large defects of the foot has been
      the use of free muscle flaps covered with skin grafts. Although this method has
      served well, some patients will experience ulceration in the weight-bearing
      surface. Three cases are reported in which small ulcerations developed in the
      heel after reconstruction of traumatic defects with muscle free flaps. All three
      patients were treated with a neurovascular island flap from the side of the great
      toe. All three patients are active young males, and all three patients have
      subsequently maintained intact skin for an average of 6.8 years (range, 5.1 to
      9.1 years).

PMID- 10088515
TI  - Cleft lip scar camouflage using dermal micrografts.
AB  - The use of dermal micrografts to camouflage cleft lip scars is a simple and
      effective method. We have used dermal micrografts, some hairbearing, to
      camouflage hypopigmented scars in 10 patients. This method improves the color of
      the scar, corrects wound distortion and direction to a certain degree, and
      enables the resultant scar to blend into the adjacent tissue more naturally.
      Unlike with other methods of scar revision, additional tissue is not sacrificed
      and new incision lines are not created.

PMID- 10088516
TI  - A custom splint for zygomatic fractures.
AB  - In the past, various materials have been applied to the zygomatic region to serve
      as a protective splint during the healing phase. Traditionally, these have been
      bulky, cumbersome, and non-conforming. This technique involves the application of
      a precut thermoplastic splint that is site-specific, lightweight, adjustable, low
      profile and universal and adapts to the anatomy of each patient.

PMID- 10088517
TI  - Modified tendon stripper for obtaining palmaris longus tendon graft.
AB  - Tendon graft harvesting is a challenging part of hand surgery. It is not only a
      time-consuming procedure but also carries the potential complications associated
      with it. Various alternatives for this procedure are presented in the literature
      to overcome these difficulties. In this paper, we are presenting a series of
      cases in which a newly modified tendon stripper was used for tendon graft
      harvesting.

PMID- 10088518
TI  - The clinical outcome of abdominoplasty performed under conscious sedation:
      increased use of fentanyl correlated with longer stay in outpatient unit.
AB  - The objective of this study was to present data supporting the effectiveness of
      performing mini and full abdominoplasties under conscious sedation with local
      anesthesia. The authors performed 20 such operations between 1994 and 1996, using
      a combination of midazolam (Versed) and fentanyl instead of general anesthesia
      (without an anesthesiologist or nurse anesthetist present). At 5- to 10-minute
      intervals, the surgeon would order the injection of 1 cc (1 mg/ml) of midazolam
      and 1 cc (50 microg/ml) of fentanyl. The amount and the interval varied based on
      the patient's level of sedation. Blood pressure, oxygen saturation, and the
      patient's response to verbal and physical stimuli were used to assess the
      sedation level. Average operating time was 147.5 minutes, and mean length of stay
      in the outpatient recovery room was 235.5 minutes. The average amounts of
      midazolam and fentanyl used were 9.4 mg (6 to 12.5 mg) and 532 microg (300 to 800
      microg), respectively. The average age of patients in this group was 41.7 years
      (28 to 63 years). Nineteen patients were discharged the same day. There were no
      surgical complications and no complication related to the sedation (such as
      respiratory or cardiac compromise). The average follow-up of these patients was
      1.2 years (range, 3 to 21 months). Correlation coefficient rates and regression
      rates were calculated. The longer the procedure, the more midazolam was used
      intraoperatively (r = 0.5, p = 0.03). However, there was no correlation between
      the length of the procedure and the amount of fentanyl used. Rather, there was a
      positive correlation demonstrating that patients who received more fentanyl
      stayed longer in the outpatient recovery area after surgery (r = 0.6, p < 0.01).
      The age of the patients and the amount of midazolam did not correlate with how
      fast they went home from the outpatient area. In conclusion, full and mini
      abdominoplasties can be performed safely using conscious sedation without
      compromising patient care or surgical outcome. Second, the survey revealed that
      patient satisfaction with these procedures performed under conscious sedation was
      very high. Third, the increased use of fentanyl, not midazolam, resulted in a
      longer stay in the outpatient unit after surgery. Nausea is a known side effect
      of narcotic analgesics, and it correlated with a higher dose of fentanyl
      administration in the patients. The authors are now routinely administering a
      dose of either droperidol or odansetron (Zofran) preoperatively (both are
      antiemetics). Previously, the ratio of midazolam and fentanyl injection was 1:1
      every 5 to 10 minutes, but now it is 2: 1 to 4: 1 every 5 to 10 minutes (a
      smaller dose of fentanyl is administered). The conscious sedation technique
      should be an option for patients and plastic surgeons in academic and community
      hospital settings if they desire.

PMID- 10088519
TI  - Plasma concentrations of lidocaine and alpha1-acid glycoprotein during and after
      breast augmentation.
AB  - Plasma levels of lidocaine and the main binding proteins of lidocaine in plasma
      alpha1-acid glycoprotein (AAG) and albumin were measured in 10 otherwise healthy
      women during and after breast augmentation. A total dose of 825 to 1280 mg of
      0.2% and 0.5% lidocaine with epinephrine corresponding to 16.3 to 21.8 mg/kg
      (mean 18.2 mg/kg) was injected in the spatium between the pectoralis muscle and
      the mammary gland. The peak plasma concentrations of lidocaine varied between
      0.96 and 3.12 microg/ml (mean 1.49 microg/ml) and occurred between 4 and 12 hours
      (mean 7.3 hours) postoperatively. The plasma concentration of AAG varied between
      0.42 and 1.73 g/liter (mean 0.49 g/liter, normal range 0.54 to 1.17 g/liter).
      There was a significant correlation between the plasma concentration of AAG and
      lidocaine. The mean concentration of albumin was 37.2 g/liter, ranging from 33 to
      42 g/liter (normal range 35 to 50 g/liter). No patient showed signs of lidocaine
      toxicity. These data indicate that a dose of 20 mg/kg of lidocaine with
      epinephrine probably is safe in breast augmentation when the drug is
      administrated as described in this study. There are significant individual
      differences in the plasma concentration curves between patients, partly explained
      by different concentrations of AAG. Further studies with a larger number of
      patients are needed to establish definitive recommendations of safe maximal
      doses.

PMID- 10088520
TI  - Analysis of breast implant capsular tissue for crystalline silica and other
      refractile phases.
AB  - This study questions previous reports of the presence of micrometer-sized areas
      of crystalline silica in pathologic tissue sections that are based exclusively on
      polarized-light microscopy. By using optical principles, it can be argued that it
      is impossible to identify unambiguously or to detect the birefringence of
      crystalline silica in 5-microm-thin sections. To clarify whether silicone,
      amorphous silica, or crystalline silica occurs in micrometer-sized moieties in
      standard 5-microm-thick tissue sections, one needs to apply a structural means of
      analysis in addition to optical microscopy. This study recommends the use of the
      laser Raman spectroscopic technique, which is very well suited to clarify this
      highly controversial issue in future pathologic studies.

PMID- 10088521
TI  - Expanded polytetrafluoroethylene threads for lip augmentation induce foreign body
      granulomatous reaction.
AB  - Especially in cases of facial aesthetic surgery, the demands of the patients are
      high. The formation of a visible and painful nodule will cause not only
      discomfort but also dissatisfaction. When alloplastic materials are used for
      facial and lip augmentation, the possibility of migration, allergic reaction, and
      formation of a foreign body granuloma is always present. Although e-PTFE is the
      most bioinert alloplastic material available, the authors could show the
      formation of a foreign body granuloma. When using e-PTFE threads for facial
      augmentation, the surgeon should keep in mind and inform the patients that the
      threads can induce a foreign body granulomatous reaction.

PMID- 10088522
TI  - George H. Monks lecture. On politics and medicine.

PMID- 10088523
TI  - Subunit principles in midface fractures: the importance of sagittal buttresses,
      soft-tissue reductions, and sequencing treatment of segmental fractures.
AB  - The patterns of midface fractures were related to postoperative computed
      tomography scans and clinical results to assess the value of ordering fracture
      assembly in success of treatment methods. A total of 550 midface fractures were
      studied for their midface components and the presence of fractures in the
      adjacent frontal bone or mandible. Preoperative and postoperative computed
      tomography scans were analyzed to generate recommendations regarding exposure and
      postoperative stability related to fracture pattern and treatment sequence, both
      within the midface alone and when combined with frontal bone and mandibular
      fractures. Large segment (Le Fort I, II, and III) fractures were seen in 68
      patients (12 percent); more comminuted midface fracture combinations were seen in
      93 patients (17 percent). Midface and mandibular fractures were seen in 166
      patients (30 percent). Midface, mandible, and nasoethmoid fractures were seen in
      38 patients (7 percent). Frontal bone and midface fractures were seen in 131
      patients (24 percent). Split-palate fractures accompanied 8 percent of midface
      fractures. Frontal bone, midface, and mandibular fractures were seen in 54
      patients (10 percent). The midface, because of weak bone structure and comminuted
      fracture pattern, must therefore be considered a dependent, less stable
      structure. Its injuries more commonly occur with fractures of the frontal bone or
      mandible (two-thirds of cases) and, more often than not (>60 percent), are
      comminuted. Comminuted and pan-facial (multiple area) fractures deserve
      individualized consideration regarding the length of intermaxillary
      immobilization. Examples of common errors are described from this patient
      experience.

PMID- 10088524
TI  - Should improved mastectomy and reconstruction alter the primary management of
      breast cancer?

PMID- 10088525
TI  - The medical professional in the next millennium.

PMID- 10088526
TI  - New times, old words, new meanings.

PMID- 10088527
TI  - Footprints of the globe: a practical look at the mechanism of orbital blowout
      fractures, with a revisit to the work of Raymond Pfeiffer.
AB  - Multiple mechanisms of orbital blowout fractures have been proposed since the
      fracture was described at the beginning of this century. The original theory of
      direct globe-to-wall contact was abandoned long ago for the more contemporary
      hydraulic and bone conduction theories. Although the more widely accepted
      theories play an obvious role in fracture generation and its associated
      complications, it is our contention that direct globe-to-wall contact is an
      important and largely unrecognized mechanism in orbital blowout fracture
      production. By means of a critical review of the historical literature and an
      analysis of patient computed tomography scans, support is presented for the
      original theory first proposed by Raymond Pfeiffer in 1943.

PMID- 10088528
TI  - Prescriptive percutaneous facial nerve mapping.

PMID- 10088529
TI  - Risk of transmission of agents associated with Creutzfeldt-Jakob disease and
      bovine spongiform encephalopathy.

PMID- 10088531
TI  - Simplified fixation for endoscopic brow lifts: self-tapping, drill-free posts.

PMID- 10088530
TI  - The surgical correction of aging eyelids.

PMID- 10088532
TI  - Reassessment of the coronal incision and subgaleal dissection for foreheadplasty.

PMID- 10088533
TI  - Reconstruction of defects involving the upper one-third of the auricle.

PMID- 10088534
TI  - Securing the nostril retainer.

PMID- 10088535
TI  - 1:50,000 epinephrine.

PMID- 10088536
TI  - Explantation.

PMID- 10088537
TI  - Use of Archimedes' law for measuring the volume of the TRAM flap in immediate
      breast reconstruction.

PMID- 10088538
TI  - Easy pinning: a new approach to phalangeal fixation.

PMID- 10088539
TI  - Phlebolithosis.

PMID- 10088540
TI  - A new, lethal form of follicular lymphoma?

PMID- 10088541
TI  - Pulmonary dirofilariasis: a clinicopathologic study of 41 lesions in 39 patients.
AB  - Forty-one cases of pulmonary dirofilariasis in 39 patients are presented. The
      patients, all Americans, were between 8 and 80 years old (median, 58 years),
      including 23 men and 16 women. Twenty-two patients were asymptomatic (56%), and
      the pulmonary nodule was discovered on chest radiographs during a routine
      physical examination. Seventeen patients (44%) presented with respiratory
      symptoms or systemic complaints. Peripheral eosinophilia was noted in only 10% of
      the patients. Radiographically, most lesions were located in the right lung
      (76%), with a predilection for the lower lobe. In five patients multifocal
      nodules were seen. All patients underwent thoracotomy with excisional lung biopsy
      or lobectomy. Pathologically, all cases featured a histiocyte-rimmed necrotic
      nodule containing fragments of a partially degenerated Dirofilaria immitis. In
      addition, adjacent lung parenchyma showed morphological features suggestive of
      other pulmonary processes such as extrinsic allergic alveolitis and/or pulmonary
      vasculitis syndromes. Three of the five patients with multiple nodules had
      solitary dirofilarial nodules and adjacent non-small cell carcinomas. The cases
      presented herein highlight the variable morphological features seen in human
      pulmonary dirofilariasis and emphasize the need to consider this diagnosis in all
      cases of necrotizing granulomas of the lung.

PMID- 10088542
TI  - Interobserver reproducibility of the Lagios nuclear grading system for ductal
      carcinoma in situ.
AB  - Several studies have shown an association between high nuclear grade or necrosis
      of ductal carcinoma in situ (DCIS) lesions and the risk of local disease
      recurrence in patients with DCIS treated surgically with less than mastectomy.
      Although criteria for separating low from high nuclear grade lesions have been
      published, no information exists regarding interobserver reproducibility (IR). To
      assess IR in the classification of DCIS, six surgical pathologists from four
      institutions used the Lagios grading system to grade 125 DCIS lesions. Before
      meeting to evaluate the cases, a training set of 12 glass slides, including cases
      chosen to present conflicting cues for classification, was mailed to the
      participants with a written criteria summary. This was followed by a working
      session in which criteria were reviewed and agreed on. The pathologists then
      graded the lesions independently. The area of interest was marked on each slide
      before grading. After initial grading, the pathologists met again to resolve
      discrepant lesion classifications. A complete agreement among raters was achieved
      in 43 (35%) cases, with five of six raters agreeing in another 45 (36%) cases. In
      no case did two raters differ by more than one grade. The pairwise kappa
      agreement values ranged from fair to substantial (0.30 to 0.61). Generalized
      kappa value indicated moderate agreement (0.46, standard error = 0.02). Kappa
      statistics for the distinction between grades 1 and 2 and 2 and 3 were 0.29 and
      0.48, respectively, (standard error = 0.02). Only one of the six raters differed
      significantly in scoring. With adherence to specific criteria, IR in the
      classification of DCIS cases can be obtained in most cases. Although these
      pathologists made a few grading system modifications, further refinements are
      needed, especially if grading will influence future therapy.

PMID- 10088543
TI  - Clinical significance of follicular lymphoma with monocytoid B cells. Non
      Hodgkin's Lymphoma Classification Project.
AB  - Although follicular lymphoma (FL) is very common in the Western world, very
      little information is available regarding the frequency and significance of
      monocytoid B cells (MBC) in FL. We recently completed a clinicopathologic study
      of 1,378 cases of non-Hodgkin's lymphoma. In this study, a research data sheet
      was designed to conduct research on several types of lymphomas, one part of which
      was evaluating the presence of intrafollicular clear cells and extrafollicular
      MBC in 326 cases diagnosed as FL by one of the pathologists (B.N.N.). For each
      case diagnosed as FL, the presence of intrafollicular clear cells or
      extrafollicular MBC was scored as pure FL (no intrafollicular clear cells or
      extrafollicular MBC), FL with intrafollicular clear cells, FL with less than 5%
      MBC, and FL with greater than 5% MBC. Of 326 cases classified as FL, 252 (77%)
      had no intrafollicular clear cells or extrafollicular MBC and therefore were
      called pure FL. In 36 cases (11%), intrafollicular clear cells were seen, but no
      extrafollicular MBC. There were no clinical differences between such cases and
      the 252 cases of pure FL. In eight cases of FL (2%), MBC clusters were rare
      (<5%). In contrast, 30 cases of FL (9%) had a prominent (>5%) proliferation of
      extrafollicular MBC; these 30 cases had a significantly shorter failure-free
      survival (P = .001) and overall survival (P = .04) than the 252 cases of pure FL.
      The shorter survival of these 30 cases appeared to be independent of the
      international prognostic index (IPI), stage, and treatment. The FFS of this group
      remained shorter than that of cases with pure FL when the analysis was restricted
      to patients treated with Adriamycin-containing regimens and either a favorable (0
      to 3) IPI score (P = .001) or advanced stage (III/IV) disease (P = .015). In
      conclusion, FL with a prominent (>5%) MBC component constitutes a substantial
      proportion (9%) of FL and has distinctive morphology, and these patients have a
      significantly shorter survival than those with pure FL.

PMID- 10088544
TI  - Amoeba angeitic lesions of the central nervous system in Balamuthia mandrilaris
      amoebiasis.
AB  - Balamuthia mandrilaris amoebiasis is a fatal disease. It primarily affects the
      nasal pyramid or the skin, producing granulomatous amoebic lesions. The amoeba
      spread from the primary nasal lesion to the meninges where they infiltrate
      vessels. Thrombotic amoebic angitis produce infarcts of the central nervous
      system substance which then become infiltrated by amoeba. The primary cutaneous
      lesion can be present for weeks or even months. However, the appearance of
      neurological disease predicts a poor prognosis, in which death usually occurs
      within a few days or weeks.

PMID- 10088545
TI  - Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung
      carcinogenesis.
AB  - Data on human papilloma virus (HPV) involvement in preneoplastic and neoplastic
      lesions of the larynx and lung are limited and conflicting. The presence of HPV
      was investigated in a series of laryngeal specimens and non-small cell lung
      carcinomas (NSCLCs). The laryngeal samples (154) comprised 14 cases with
      hyperplasia without dysplasia, 49 with dysplasia, and 91 squamous cell carcinomas
      (SqCCs). The NSCLCs included 31 SqCCs, 32 adenocarcinomas, and 5 undifferentiated
      large cell carcinomas. Furthermore, we examined, for HPV DNA sequences, 14
      bronchial metaplastic squamous lesions located next to cancerous areas. We used a
      sensitive nested polymerase chain reaction assay (NPCR), dot blotting, and in
      situ hybridization. The findings were correlated with clinicopathologic features
      of the patients. In the laryngeal specimens, NPCR analysis showed HPV DNA in 20
      (13%) of the 154 specimens. Notably, 19 of 20 HPV-positive cases were carcinomas
      and only one was a mild dysplastic lesion. Typing of the carcinomas showed single
      HPV 6, 16, 18, and 33 infection in 1 (1.1%), 12 (13.2%), 2 (2.2%), and 1 (1.1%)
      samples, respectively, and HPV 6/33, 16/33, and 6/18 coinfection in three
      carcinomas. In situ hybridization findings were in agreement with PCR results,
      with the exception of two cases in which HPV 18 DNA was detected only by PCR. HPV
      was more frequently observed in heavy smokers than in patients with low daily
      cigarette consumption and nonsmokers (P = .03). There was no correlation between
      virus infection and gender, grade, and lymph node status of the carcinomas. None
      of the NSCLCs or adjacent metaplastic squamous epithelium contained HPV DNA
      sequences. The presented data suggest a contributory role of HPV in late stages
      of laryngeal carcinogenesis, because all premalignant lesions were negative but
      one. This study does not support a potential role of HPV in the development of
      NSCLCs.

PMID- 10088546
TI  - Detection of loss of heterozygosity on chromosome 9q22.3 in microdissected
      sporadic basal cell carcinoma.
AB  - Identification of loss of heterozygosity (LOH) at specific genetic loci in cancer
      cells suggests the presence of a tumor suppressor gene within the deleted region.
      A basal cell carcinoma (BCC) susceptibility gene, human homolog of drosophila
      patched (PTC), has been recently cloned and localized on chromosome 9q22.3.
      Mutation and deletion of this region has been reported in BCCs using frozen tumor
      tissue. The objective of this study was to test whether LOH of human PTC on
      chromosome 9q22 could be detected in archival sporadic BCCs. We studied 20
      randomly selected sporadic BCCs by microdissection and polymerase chain reaction
      using paraffin-embedded, formalin-fixed material on glass slides. In all cases,
      analysis was performed with the polymorphic markers D9S53, D9S15, D9S287, and
      D9S303. The LOH frequencies were 30%, 42%, 56%, and 75% with D9S15, D9S287,
      D9S53, and D9S303, respectively. LOH at 9q22 was identified in 12 of 20 cases
      (60%) with at least one marker. Seven cases showed LOH with two markers, two
      cases with three markers, and one case showed LOH with all four markers. The
      results indicate that BCC LOH can be frequently identified in paraffin-embedded
      BCC after routine processing.

PMID- 10088547
TI  - Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal
      metaplasia of the stomach.
AB  - The histological distinction between intestinal metaplasia involving the distal
      esophagus (Barrett's esophagus [BE]) and intestinal metaplasia of the stomach has
      important clinical implications and can be difficult even with the use of
      histochemical mucin stains. Cytokeratin (CK) 7 and 20 are cytoplasmic structural
      proteins that show restricted expression in normal and malignant epithelia of the
      gastrointestinal tract. The aim of this study was to determine the use of CK7 and
      20 expression in the histological distinction of BE from gastric intestinal
      metaplasia. CK7 and 20 immunostaining was performed on randomly selected surgical
      resection (n = 31) and biopsy specimens (n = 34) from patients with long-segment
      BE and gastric resection specimens (n = 11) and gastric cardia biopsy specimens
      (n = 13) in patients with histological evidence of intestinal metaplasia. A
      unique pattern of immunoreactivity designated the Barrett's CK7/20 pattern showed
      superficial CK20 staining and strong CK7 staining of both superficial and deep
      glands in 29 of 31 (94%) esophageal resection specimens and 34 of 34 (100%)
      esophageal biopsy specimens form patients with long-segment BE. A Barrett's
      CK7/20 pattern was not observed in gastric cardia biopsy specimens (n = 13) or
      gastric resection specimens (n = 11) in patients with histological evidence of
      intestinal metaplasia. The sensitivity, specificity, and positive predictive
      value of a Barrett's CK7/20 pattern for a diagnosis of long-segment BE was 97%,
      100%, and 100%, respectively. CK7 and 20 reactivity patterns can reliably
      identify the location of intestinal metaplasia in the esophagus and stomach using
      histological material from both routine endoscopic biopsy and surgical resection
      specimens.

PMID- 10088548
TI  - Chromosomal analysis of renal angiomyolipoma by comparative genomic
      hybridization: evidence for clonal origin.
AB  - Angiomyolipoma has long been considered a hamartomatous polyclonal proliferation.
      However, recent molecular analyses have indicated that these tumors may be clonal
      neoplasms rather than polyclonal proliferations. We investigated chromosomal
      imbalances in angiomyolipoma by comparative genomic hybridization. DNA was
      extracted from archival paraffin-embedded and frozen tissues of 12
      angiomyolipomas (10 usual variant, two epithelioid variant). The 10
      angiomyolipomas of the usual variant included bilateral tumors from one tuberous
      sclerosis patient. Fluorescence ratio distributions from tumor hybridizations
      were compared with those from control hybridizations to detect changes in DNA
      copy number with high sensitivity and specificity. We identified 20 chromosomal
      imbalances in seven sporadic angiomyolipomas, including both tumors of the
      epithelioid variant. The remaining five tumors, including the two angiomyolipomas
      from a tuberous sclerosis patient, were devoid of chromosomal imbalances. Seventy
      five percent of the imbalances were partial or whole chromosomal deletions
      involving disparate genomic regions, some of which have previously been
      associated with tumors of adipose tissue and smooth muscle tumors. Four
      angiomyolipomas of the usual variant showed 5q deletions with a common region of
      deletion spanning 5q33 to q34. In two tumors, deletion on 5q was the sole
      abnormality. One epithelioid angiomyolipoma showed 5q gain encompassing the same
      region in addition to other alterations. We concluded that (1) Chromosomal
      imbalances are common in renal angiomyolipomas; (2) Presence of clonal genomic
      alterations lends further support to the neoplastic pathogenesis of these tumors;
      (3) The 5q33-q34 region may contain a tumor suppressor gene significant in the
      histogenesis of some renal angiomyolipomas.

PMID- 10088549
TI  - Altered expression of gamma-glutamyl transpeptidase in human tumors.
AB  - Elevated levels of gamma-glutamyl transpeptidase (GGT) activity and intracellular
      glutathione in tumor cells have been correlated with resistance to several
      classes of chemotherapeutic drugs. In this study, the first comprehensive
      analysis of GGT expression in human malignant neoplasms, 451 tumors were
      immunostained with an antibody directed against a c-terminus peptide of the human
      GGT protein. Analysis of the immunostaining revealed that GGT was expressed in 22
      of 44 lung carcinomas and 16 of 22 ovarian surface epithelial carcinomas,
      although normal pulmonary and ovarian epithelium are GGT-negative. The tumor
      samples were obtained from patients before the start of therapy; therefore, GGT
      was not induced by radiation or chemotherapy. There was no GGT expression in
      mesotheliomas, Hodgkin's disease, non-Hodgkin's lymphomas, melanomas, basal cell
      carcinomas, and most soft tissue sarcomas, all of which are derived from GGT
      negative cells. Carcinomas arising from some GGT-positive epithelium retained
      their GGT-positive phenotype. These included renal cell carcinomas,
      hepatocellular and cholangiocarcinomas, and carcinomas of the prostate and
      thyroid whereas both pancreatic adenocarcinomas and infiltrating carcinomas of
      the breast showed a wide range of GGT expression. Further studies are underway to
      determine whether expression of GGT plays a role in the inherent resistance of
      some tumors to alkylating agents and other classes of chemotherapeutic drugs.

PMID- 10088550
TI  - Somatic mutation analysis of IgH variable regions reveals that tumor cells of
      most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell
      lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes.
AB  - The cell of origin of parafollicular (monocytoid) B cell lymphoma (PBCL), splenic
      marginal zone lymphoma (SMZL), and hairy cell leukemia (HCL) is controversial. To
      better understand the relationship between these low-grade B-cell neoplasms, we
      analyzed the nucleotide sequences of the rearranged immunoglobulin heavy (IgH)
      chain variable (V) region of the clonal population of cells in five cases of
      PBCL, four cases of SMZL, and seven cases of HCL to determine whether these
      neoplasms could be differentiated by the degree of somatic mutation in the IgH V
      gene or by the IgH V gene family usage. DNA was extracted from diagnostic
      material and clonality confirmed by PCR. The DNA was reamplified using V heavy
      chain family specific primers, and the amplicons were sequenced. Sequences were
      compared with germline IgH V gene sequences, and base changes were determined to
      be silent or to represent amino acid replacements by using three different
      methods. Four of five (80%) cases of PBCL, three of four (75%) cases of SMZL, and
      three of seven (43%) cases of HCL showed evidence of antigen selection,
      suggesting that these neoplasms involved clonal expansions of postgerminal center
      memory lymphocytes. Only SMZL showed a preferential usage of V(H)1 family genes.

PMID- 10088551
TI  - The immunohistochemical diagnosis of epithelial mesothelioma.
AB  - Although it is generally accepted that immunohistochemistry can assist in
      distinguishing between epithelial mesotheliomas and metastatic adenocarcinomas to
      the serosal membranes, a great deal of controversy exists regarding not only the
      practical value of some of the markers currently used, but also which should be
      included as part of the routine diagnostic panel. Until recently, these panels
      consisted primarily of antibodies that stained adenocarcinomas but not
      mesotheliomas. Over the last few years, however, markers that are commonly
      expressed in mesotheliomas but not in adenocarcinomas have been recognized. The
      focus of this review is on those markers for which there is an indication that
      they have a practical use in the diagnosis of mesothelioma. Special emphasis is
      placed on those which have been most recently recognized.

PMID- 10088552
TI  - Detection of EWS-FLI-1 fusion in Ewing's sarcoma/peripheral primitive
      neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed
      paraffin-embedded tissue.
AB  - The balanced translocation t(11;22)(q24;q12) is specific for the Ewing's
      sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the
      EWS/FLI-1 fusion transcript, which can be detected by reverse transcription
      polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in
      situ hybridization (FISH) to show the translocation; however, most of these have
      been performed on cell lines or touch preparations and short-term cultures of
      tumors. Moreover, the existing probes generally have shown only the break in the
      specific chromosomes rather than the translocation itself. We describe our
      findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1)
      and directly show the translocation as juxtaposed red-green signals on der(22) in
      nuclei extracted from formalin-fixed, paraffm-embedded tissues. After
      establishing the specificity of the probes (on metaphase spreads and interphase
      nuclei in two translocation-positive cell lines and normal peripheral blood
      lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar
      rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary
      myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion
      signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random
      overlapping signals were present in 2% and 4% of nuclei, whereas the remaining
      eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in
      10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe
      pair is a specific and sensitive method of detecting t(11;22) on routinely
      processed tissue and can be useful in the differential diagnosis of ES/PNETs from
      other small round blue cell tumors when only fixed tissue is available.

PMID- 10088553
TI  - Basement membrane patterns, gelatinase A and tissue inhibitor of
      metalloproteinase-2 expressions, and stromal fibrosis during the development of
      peripheral lung adenocarcinoma.
AB  - To clarify the process and mechanisms of the development and progression of
      peripheral lung adenocarcinoma, we investigated the relationships among the
      patterns of basement membrane (BM), stromal fibrosis, and the expressions of
      gelatinase A and tissue inhibitor of metalloproteinases-2 (TIMP-2) in 33 lesions
      of atypical alveolar cell hyperplasia (AAH) and 48 lesions of lung
      adenocarcinoma, including 24 lesions of bronchioloalveolar carcinoma (BAC). We
      found that the architecture of alveolar BM was intact in all 33 AAH lesions and
      11 nonsclerosing BAC lesions that formed no central scar, suggesting that these
      lesions are early-stage intraepithelial neoplasia. The preexistent BM of the lung
      was disrupted, and the BM components around the neoplastic glands were disrupted
      or absent in the area of the central scar of some sclerosing BAC lesions with
      collapse fibrosis alone (2 of 4) and in those of all of the adenocarcinoma
      lesions associated with desmoplastic stromal fibrosis (nine sclerosing BAC and 24
      non-BAC tumors). These results suggested that, in lung adenocarcinomas,
      destruction of the BM was correlated with the formation of a central scar,
      particularly with desmoplasia. It is likely that adenocarcinomas with a central
      scar are advanced and invasive cancers potentially having metastatic activity.
      The expression of gelatinase A and TIMP-2 was associated with central scar
      formation as well as with destruction of the BM components. Both the neoplastic
      and stromal cells expressed gelatinase A and TIMP-2 and probably play a role in
      tumor cell invasion.

PMID- 10088554
TI  - Osteonectin expression correlates with clinical outcome in thin cutaneous
      malignant melanomas.
AB  - Osteonectin, also termed BM40 or SPARC (secreted protein, acidic and rich in
      cysteine) is a multifunctional glycoprotein involved in tissue mineralization,
      cell-extracellular matrix interactions as well as angiogenesis. It has been
      suggested that osteonectin may play a key role in the process of tumoral invasion
      and metastasis in certain malignancies. In this study, we reviewed the clinical
      records and the histopathologic slides of 188 thin cutaneous malignant melanomas
      (< or = 0.75 mm). Among them, 12 cases underwent progression and were selected
      for the study. Osteonectin expression was investigated by immunohistochemistry in
      these 12 patients and 24 matched controls who did not undergo progression.
      Osteonectin staining was correlated with clinical outcome and other
      clinicopathologic parameters. Progression-free and disease-specific survival
      rates were calculated with the Kaplan-Meier method and their differences were
      evaluated by the log rank test. Overall, immunoreactivity for osteonectin was
      found in 23 (63.8%) cases. Eighteen cases (50%) displayed staining in 1% to 50%
      of neoplastic cells whereas five cases (13.8%) showed a diffuse positivity in
      more than 50% of the tumor cells. Osteonectin expression was significantly
      correlated with risk of progression (P = .01), incidence of distant metastases (P
      = .005) and survival (P = .03). There was a higher incidence of osteonectin
      positive tumors in cases that did experience regional lymph node metastases
      versus those cases that did not, but that difference did not reach statistical
      significance (P = .06). No significant correlation was found between osteonectin
      expression and other clinicopathologic features, including age, sex, site,
      histotype, Clark's level, presence of regression, presence of inflammatory
      response, and tumor growth phase. Our data showed that osteonectin expression is
      a predictor of clinical outcome in thin cutaneous melanomas.

PMID- 10088555
TI  - Atypical immature metaplasia (AIM) of the cervix: is it related to high-grade
      squamous intraepithelial lesion (HSIL)?
AB  - Atypical immature metaplasia (AIM) is a poorly characterized cervical lesion with
      uncertain biological and clinical significance. AIM shares some, but not all,
      morphological features of squamous intraepithelial lesions (SILs). SILs are
      characterized by human papillomavirus (HPV) positivity and increased cellular
      proliferation, but these features have not been fully evaluated in AIM. Genomic
      DNA was extracted from 27 microdissected cervical biopsy specimens diagnosed as
      AIM. HPV DNA was detected by polymerase chain reaction (PCR), using two different
      sets of L1 gene consensus primers. HPV types were identified by sequence analysis
      of PCR products and comparison with published HPV sequences. The cell
      proliferation index was assessed by immunohistochemical staining for Ki-67 (MIB
      1) antigen and expressed as the percentage of Ki-67-positive cells. Comparison
      groups included normal cervix (n = 10) and low-grade (LSILs, n = 19) and high
      grade squamous intraepithelial lesions (HSILs, n = 11). Intermediate- or high
      risk HPV DNA was detected in 67% (18 of 27) of AIM cases. Low-risk HPV DNA was
      not detected in any of the specimens. The Ki-67 index in AIM (mean, 33.0 +/-
      20.3; median, 29) was comparable to that of LSILs (mean, 21.4 +/- 4.6; median,
      21) and was significantly higher than that of normal cervix (mean, 11.0 +/- 2.1;
      median, 11) (P< .01) and lower than that of HSILs (mean, 60.4 +/- 13.2; median,
      60) (P < .01). Of the cases with available follow-up, HPV-positive AIMs were
      significantly more likely to have a concurrent or subsequent diagnosis of typical
      HSIL (12 of 15, 80%) than HPV-negative AIMs (one of six, 45%) (P = .014). The
      wide range of Ki-67 indices and variable HPV status in AIM suggest that AIM
      represents a heterogeneous group of lesions including bona fide HSILs (high-risk
      HPV-positive, high Ki-67 index), antecedents (precursors?) of HSILs (high-risk
      HPV-positive, low to moderate Ki-67 index), and benign reactive conditions (HPV
      negative, variable Ki-67 index). HPV testing may be useful in the assessment of
      atypical epithelial proliferations of the cervix for which a diagnosis of AIM is
      considered.

PMID- 10088556
TI  - Translocation (11;22)(q24;q12) in a small cell tumor of the thigh in a 2-year-old
      boy: immunohistology, cytogenetics, molecular genetics, and review of the
      literature.
AB  - A case of a 2-year-old boy with a palpable mass in the left thigh is presented.
      Incisional biopsy was performed and subsequent histopathological examination
      revealed an infiltrative tumor composed of relatively large cells. The tumor
      cells were immunoreactive for vimentin and keratin, but not for desmin or smooth
      muscle actin. Cytogenetic analysis showed a 46,XY,t(11;22)(q24;q12) karyotype.
      The translocation (11;22)(q24;q12) is said to be characteristic for the family of
      Ewing's sarcoma and related tumors. As a result of the t(11;22)(q24;q12) the EWS
      gene on chromosome 22q12 joins the 3' part of FLI-1 gene on chromosome 11q24,
      which encodes a member of the ets family of transcriptional regulators. Using
      reverse transcription polymerase chain reaction (RT-PCR) a corresponding EWS-FLI
      1 fusion product was detected. Additional immunohistological staining for
      p30/p32MIC2, which is suggestive, but not specific for Ewing's sarcoma, appeared
      to be weakly positive. In the current case a diagnosis of Ewing's sarcoma was
      considered unlikely, because of the location of the tumor and the
      immunohistological profile. Nevertheless it was decided to treat the patient
      according to a Ewing's sarcoma protocol based on the genotype of the tumor. The
      findings were compared with other extraosseous pediatric small cell tumors
      showing the t(11;22)(q24;q12) described in the literature.

PMID- 10088557
TI  - Leiomyoma of the uterus showing skeletal muscle differentiation: a case report.
AB  - A case of uterine leiomyoma with skeletal muscle differentiation is described.
      The patient is a 40-year-old woman who underwent abdominal hysterectomy and left
      salpingo-oophorectomy for fibroids. Evidence of skeletal muscle differentiation
      was evident at light and electron microscopy in one out of three "ordinary"
      leiomyomas. This was also shown by positive immunoreactions with antiskeletal
      muscle actin and myoglobin antisera. To our knowledge, this is the second case
      reported of the occurrence of skeletal muscle differentiation within a uterine
      leiomyoma and highlights the divergent differentiating potential of smooth muscle
      cells.

PMID- 10088558
TI  - Expression of androgen receptors in five mammary myofibroblastomas in both sexes.

PMID- 10088559
TI  - Intramural coronary artery dysplasia of the ventricular septum and sudden death.

PMID- 10088560
TI  - Expression of the 67-KD laminin-binding protein in human lymphomas.

PMID- 10088561
TI  - Functional outcome after laparoscopic or open Nissen fundoplication: a follow-up
      study.
AB  - OBJECTIVE: To compare the results of open and laparoscopic fundoplication.
      DESIGN: Nonrandomized controlled study with a 3-year follow-up. PATIENTS AND
      METHODS: Fifty-seven consecutive patients with erosive reflux esophagitis
      underwent laparoscopic (30 patients) or open (27 patients) fundoplication.
      INTERVENTIONS: Interview by an independent person. In addition, 52 patients (91%)
      underwent postoperative endoscopy, and 38 patients (67%) underwent esophageal 24
      hour pH recording. RESULTS: Temporary dysphagia was reported by 20 patients (67%)
      after laparoscopic and by 11 (41%) after open fundoplication (P = .05). There
      were no differences between groups concerning incidence of persistent dysphagia
      (20% vs 18%, respectively) and mild to no reflux symptoms (97% vs 100%,
      respectively). In addition, bloating (50% vs 63%, respectively) and increased
      flatus (77% vs 78%, respectively) were equally common. Visual analog scale scores
      for dysphagia, bloating, and increased flatus were 0.6, 2.4, and 4.3,
      respectively, in the laparoscopic and 0.6, 3.5, and 3.4, respectively, in the
      open groups. Normal belching ability was reported by 12 patients (40%) after
      laparoscopic and by 20 (74%) after open fundoplication (P = .01). Visick grade 1
      or 2 was reported by 21 patients (70%) after laparoscopic and by 24 (89%) after
      open fundoplication (P = .08). Defective fundic wrap was detected in 4 patients
      (13%) in the laparoscopic and in none in the open group. In addition, abnormal
      results of 24-hour pH recording were found in 4 patients (22%) after laparoscopic
      and in 2 (10.5%) after open fundoplication. CONCLUSION: From a functional point
      of view, both techniques were equally effective except concerning belching
      ability and temporary dysphagia.

PMID- 10088562
TI  - Association of increased immunostaining for inducible nitric oxide synthase and
      nitrotyrosine with fibroblast growth factor transformation in pancreatic cancer.
AB  - BACKGROUND: Despite recognition of the devastating malignant potential of
      pancreatic cancer, the exact pathophysiological events contributing to tumor
      growth, vascular invasiveness, and hepatic metastasis remain to be elucidated.
      METHODS: Twelve human pancreatic adenocarcinomas were evaluated using
      immunohistochemical and in situ hybridization techniques for the appearance of
      the angiogenic and neurogenic growth factors, acidic fibroblast (FGF-1) and basic
      fibroblast growth factor (FGF-2), and their high-affinity receptors. Since FGF
      biological processes appear to be regulated by oxidant stress, tumors were
      examined further for the immunoappearance of inducible nitric oxide synthase
      (iNOS) and nitrotyrosine. RESULTS: Compared with normal human pancreatic tissue,
      tumor specimens exhibited varying levels of enhanced staining for FGF ligands and
      receptors. The increased appearance of FGF-1 and FGF-2 proteins was accompanied
      by increased detection of messenger RNA encoding each growth factor. In addition,
      these pancreatic tumors demonstrated the overexpression of iNOS and
      immunostaining of nitrotyrosine compared with normal pancreatic tissue.
      CONCLUSIONS: The enhanced expression of FGF and FGF receptors suggests that these
      polypeptide mitogens may serve as important mediators of growth and of angiogenic
      and metastatic responses associated with pancreatic tumors, not seen in normal
      pancreatic tissue. Furthermore, we provide the first indication of increased
      expression of iNOS and protein tyrosine nitration, thereby predicting the
      potential involvement of oxidant stress during development and progression of
      pancreatic adenocarcinoma.

PMID- 10088563
TI  - Tikhoff-Linberg procedure for bone and soft tissue tumors of the shoulder girdle.
AB  - OBJECTIVE: To evaluate complications and the oncological and intermediate-term
      functional results in patients with bone and soft tissue tumors of the shoulder
      girdle who were managed with interscapulothoracic resection (Tikhoff-Linberg
      procedure). DESIGN: Case series of 19 consecutive patients during a 10-year
      period at a mean follow-up of 6.3 years (range, 1-11 years). SETTING: University
      hospital; referral center for musculoskeletal tumor surgery. PATIENTS: The
      initial diagnosis in this consecutive series of patients with shoulder girdle
      tumors requiring the Tikhoff-Linberg procedure was chondrosarcoma in 7 patients,
      Ewing sarcoma in 3 patients, malignant fibrous histiocytoma in 3 patients,
      solitary metastasis of thyroid carcinoma in 2 patients, osteosarcoma, synovial
      sarcoma, angiosarcoma, ancd neurofibrosarcoma in 1 patient each. According to the
      Musculoskeletal Tumor Society staging system, there were 6 in surgical stage IB,
      10 in stage IIB, and 3 in stage III. Nine tumors involved the proximal humerus, 8
      were located in the scapula or surrounding soft tissues, 1 in the lateral
      clavicle, and 1 in the acromioclavicular joint. INTERVENTIONS: For reconstruction
      of the proximal humerus after en bloc tumor resection an isoelastic cemented
      shoulder tumor prosthesis was inserted in every patient to restore arm length.
      MAIN OUTCOME MEASURES: Complications, and oncological and intermediate-term
      functional results. RESULTS: Twelve patients were alive with no evidence of
      disease. One of these patients died of nontumorous disease 2 years after surgery.
      One patient is alive with pulmonary metastases after 12 months. Six patients died
      of metastases at a mean (SD) interval of 18 months (range, 3-35 months)
      postoperatively. Two of these patients had additional local recurrence. A deep
      infection necessitated the explantation of the prosthesis in 1 patient. The mean
      functional score and SD according to the rating system of the Musculoskeletal
      Tumor Society was 72%+/-14% (range, 33%-87%) for the 12 surviving patients
      evaluated. Major complications (1 infection and 2 local recurrences) that may be
      attributed to the procedure occurred in 3 of the 19 patients. CONCLUSION: Despite
      an overall complication rate of 74% the Tikhoff-Linberg procedure proved to be a
      valuable surgical procedure for extended tumors of the shoulder girdle for
      functional and oncological outcome and is superior to forequarter amputation.

PMID- 10088564
TI  - Parathyroid autotransplantation during thyroidectomy: is frozen section
      necessary?
AB  - OBJECTIVE: To evaluate the accuracy of parathyroid gland identification and the
      need for routine frozen section examination before parathyroid
      autotransplantation during thyroidectomy. DESIGN: A prospective case series.
      SETTING: An endocrine surgical unit. PATIENTS: From January 1, 1995, to December
      31, 1997, parathyroid autotransplantation was attempted for devascularized or
      inadvertently removed glands in 152 (33.7%) of 450 patients during thyroidectomy.
      Before autotransplantation, a biopsy specimen of the transplanted tissue was sent
      for histological examination without frozen section confirmation. MAIN OUTCOME
      MEASURES: Positive identification of parathyroid tissue in microscopic
      examination. RESULTS: Of 179 attempted autotransplantations of parathyroid
      glands, parathyroid tissue was confirmed in 167 biopsy specimens (93.3%).
      Incorrect identification of parathyroid gland occurred in 12 instances. The
      tissue mistaken as parathyroid gland included fat in 6 cases, thyroid tissue in 4
      cases, lymph node in 1 case, and thymus in 1 case. Transplantation of at least 1
      parathyroid gland (range, 1-3) was confirmed in 144 patients. For patients with
      confirmed parathyroid autotransplantation at risk of hypoparathyroidism (n =
      112), postoperative transient hypocalcemia occurred in 22 (19.6%), while no
      patient developed any permanent hypocalcemia during a median follow-up of 6
      months. CONCLUSIONS: Devascularized or inadvertently removed parathyroid glands
      can be identified expeditiously without routine frozen section during thyroid
      surgery. Immediate autotransplantation should be performed and permanent
      hypoparathyroidism can be avoided with this measure.

PMID- 10088565
TI  - Association of preoperative biliary stenting with increased postoperative
      infectious complications in proximal cholangiocarcinoma.
AB  - BACKGROUND: The indications for preoperative biliary stenting in patients with
      obstructive jaundice are controversial. We evaluated the effect of preoperative
      biliary stenting on bacterobilia and infectious complications following surgical
      treatment of proximal cholangiocarcinoma. DESIGN: A retrospective review was
      performed of all patients undergoing surgical treatment of proximal
      cholangiocarcinoma. SETTING: A metropolitan cancer surgery service. PATIENTS AND
      METHODS: Seventy-one patients underwent palliative biliary bypass or curative
      resection of proximal cholangiocarcinoma from March 1, 1991, to April 1, 1997,
      and were entered into a prospective database. Forty-one patients underwent
      preoperative biliary intubation and stent placement. We analyzed patient,
      nutritional, laboratory, and operating room factors. Statistical evaluation was
      performed using Student t test and chi2 analysis. MAIN OUTCOME MEASURE: Data were
      recorded for a history of cholangitis, operative time, amount of blood loss,
      incidence of intraoperative bacterobilia, proportion of patients with
      postoperative infectious and noninfectious complications, and length of hospital
      stay. RESULTS: All patients (n = 14) with a history of preoperative cholangitis
      had been subjected to previous endoscopic retrograde cholangiopancreatography
      and/or percutaneous transhepatic biliary drainage. Groups were equivalent for
      risk for comorbidity, proportion undergoing curative vs palliative procedures,
      time spent in the operating room, and amount of blood loss. Patients with stents
      had a significantly lower bilirubin level (P = .005). Patients with stents had a
      significantly increased risk for bacterobilia (P = .001) and infectious
      complications (P = .03). Bacterobilia was present in 11 (100%) of 11 patients
      undergoing endoscopic stenting and in 15 (65%) of 23 patients undergoing
      percutaneous stenting. There was no increased risk for noninfectious
      complications, length of hospital stay, or mortality in patients with stents. In
      10 (59%) of 17 patients with postoperative infectious complications and positive
      findings of intraoperative bile culture, the organism was synonymous.
      CONCLUSIONS: Preoperative biliary stenting in proximal cholangiocarcinoma
      increases the incidence of contaminated bile and postoperative infectious
      complications. Endoscopic stents frequently do not relieve jaundice in high
      biliary obstruction and are rarely indicated, especially in light of their high
      contamination rate.

PMID- 10088566
TI  - Are expandable metallic stents better than conventional methods for treating
      difficult intrahepatic biliary strictures with recurrent hepatolithiasis?
AB  - BACKGROUND: Conventional methods for treating patients with recurrent
      hepatolithiasis associated with complicated intrahepatic biliary strictures
      include balloon dilatation of the intrahepatic biliary strictures, lithotripsy,
      and the clearance of difficult stones as completely as possible, with the
      placement of an external-internal stent for at least 6 months. After these
      modalities are used, symptomatic refractory strictures remain. Recently we used
      internal Gianturco-Rosch metallic Z stents to treat patients who had refractory
      strictures. OBJECTIVE: To compare therapeutic results and complications of an
      internal expandable metallic Z stent with those of repeated external-internal
      stent placement. STUDY DESIGN: Case-control study. SETTING: A referral center.
      PATIENTS: From January 1992 to December 1996, 18 patients with recurrent
      hepatolithiasis and complicated intrahepatic biliary strictures underwent
      percutaneous dilatation of stricture and transhepatic percutaneous
      cholangioscopic lithotomy for recurrent stones. After their stones were
      completely cleared, their biliary strictures failed to dilate satisfactorily. The
      patients were randomly enrolled into 2 groups: group A (7 patients), who received
      an expandable metallic Z stent, and group B (11 patients), who had repeated
      placement of external-internal stents. INTERVENTIONS: Percutaneous stricture
      dilatation, electrohydraulic lithotripsy, balloon dilatation, percutaneous
      transhepatic cholangioscopic lithotomy, and biliary stenting by a Silastic
      external-internal catheter or a modified Gianturco-Rosch expandable metallic Z
      stent (for an internal stent). MAIN OUTCOME MEASURES: The number of procedures,
      days in hospital, procedure-related complications, incidents of stone recurrence
      and recurrence of cholangitis, readmissions to the hospital, treatment sessions
      required, and mortality rate. Patients' limitations in ordinary activities were
      also compared. RESULTS: The follow-up period ranged from 28 to 60 (40.7+/-12.7
      [mean +/- SD]) months in group A and from 28 to 49 (36.0+/-7.2) months in group
      B. Fewer group A patients (3 [43%]) than group B patients (8 [73%]) tended to
      have recurrent cholangitis and to require readmission to the hospital, but this
      was not statistically significant (P = .33). When their cumulative probability of
      a first episode of cholangitis during follow-up was compared, however, it was
      significantly lower in patients treated with a metallic stent (P = .04). Compared
      with group B patients, group A patients had less frequent recurrence of stones
      (0% vs 64%; P = .01), fewer procedures for the clearance of biliary stones or
      sludge (1.7+/-2.2 vs 6.4+/-4.3; P = .03), and shorter hospital stays (8.0+/-11.5
      days vs 17.0+/-12.0 days; P = .07). No patients in group A experienced limitation
      in ordinary activities, whereas 7 patients in group B did (P<.02). CONCLUSIONS:
      Compared with the repeated placement of external-internal stents, the use of a
      metallic internal stent effectively decreases stone recurrence, simplifies
      further procedures, and is more convenient. Its use is suggested as an
      alternative choice in the treatment of recurrent hepatolithiasis with refractory
      intrahepatic biliary strictures.

PMID- 10088567
TI  - Insulin's anabolic effect is influenced by route of administration of nutrients.
AB  - OBJECTIVE: To determine if the anabolic effects of intravenous insulin on protein
      kinetics could be exploited in the enterally fed trauma victim. DESIGN:
      Randomized, crossover control protocol. SETTING: Level I trauma center. PATIENTS:
      Ten trauma patients with an Injury Severity Score higher than 20. Exclusion
      criteria included diabetes mellitus, pregnancy, steroid use, and aged younger
      than 18 years or older than 65 years. INTERVENTIONS: Within the first 24 hours of
      admission to the intensive care unit, each patient had a transpyloric feeding
      tube inserted radiographically. Enteral nutrition was provided with a protein
      supplement (Ensure, Ross Laboratories, Columbus, Ohio) and Promod, supplemented
      with protein powder to supply 1.5 g/kg per day of protein and 156.9 kJ/kg per
      day. Intravenous insulin was provided at 0.043 U/kg per hour beginning on the
      second or fourth day. MAIN OUTCOME MEASURES: Urinary nitrogen balance and 3
      methylhistidine excretion rates were measured at the end of the third and fifth
      days. Plasma glucose, insulin, and C-peptide levels were obtained at these same
      times. RESULTS: Urinary nitrogen balance was not significantly different with or
      without the administration of insulin (-4.58+/-50.1 mg/kg per day vs -9.38+/-50.9
      mg/kg per day, respectively). 3-Methylhistidine excretion rates did not change
      significantly with or without the administration of insulin (5.77+/-0.67
      micromol/kg per day vs 6.15+/-0.43 micromol/kg per day, respectively). Serum
      insulin levels did not differ significantly when exogenous infusions were added
      (57.8+/-17.9 microU/mL vs 82.1+/-44.9 microU/mL), but serum C-peptide levels did
      decrease significantly when exogenous insulin was added (5.11+/-3.2 microU/mL vs
      10.28+/-3.5 microU/mL; P = .04). Serum glucose levels decreased significantly
      when insulin was administered (5.8+/-0.4 mmol/L [104.6+/-7.2 mg/dL] vs 7.7+/-0.4
      mmol/L [138.1+/-7.4 mg/dL; P =.004). CONCLUSION: The anabolic effect of
      intravenous insulin on protein kinetics is not evident when nutrition is provided
      enterally in the trauma victim.

PMID- 10088568
TI  - Transition from open to laparoscopic fundoplication: the learning curve.
AB  - BACKGROUND: Two of us (B.C.S. and C.W.D.) began performing laparoscopic
      fundoplication in 1992. We have always designated the resident as the operating
      surgeon. OBJECTIVE: To determine the time necessary for both experienced surgeons
      and residents to become proficient in laparoscopic fundoplication. DESIGN: The
      medical records of 241 consecutive patients undergoing laparoscopic
      fundoplication were reviewed. This period started with the implementation of the
      procedure in January 1992 and ended in March 1998. For 3 consecutive years,
      residents were given a questionnaire regarding their confidence in performing
      laparoscopic fundoplication. RESULTS: Laparoscopic fundoplication was attempted
      in 241 patients and completed in 203 patients (84%). Comparing the first 25
      attempted laparoscopic fundoplications with the second 25, there were 14
      conversions (56%) vs 4 conversions (16%) (P<.01). Average operative times
      decreased from 236 to 199 minutes (P<.05), and the intraoperative complication
      rates were 5 (20%) and 1 (4%), respectively. Subsequently, the conversion rate
      stabilized at 2%. The operative time continued to decline to an average of 99
      minutes for the last 25 laparoscopies. Senior residents and recent graduates
      returning the questionnaire performed an average of 112 laparoscopic procedures,
      including 15.7 laparoscopic fundoplications. They felt comfortable with the
      procedure after performing an average of 10.6 operations. CONCLUSIONS: The
      learning curve is very steep for the first 25 laparoscopic fundoplications for
      experienced surgeons. However, improvements, as judged by decreases in operative
      time, conversion rate, and intraoperative complications, continue to occur after
      100 cases. Under supervision, residents can become comfortable with this
      procedure after about 10 to 15 procedures.

PMID- 10088569
TI  - Growth hormone attenuates tumor necrosis factor alpha in burned children.
AB  - BACKGROUND: Recombinant human growth hormone (rhGH) has been shown to favorably
      modulate the acute-phase response and may improve the clinical outcome.
      OBJECTIVE: To examine whether rhGH attenuates the elevated tumor necrosis factor
      alpha (TNF-alpha) levels that correlate with increased multiorgan failure and
      mortality in burned adults and children. DESIGN: Twenty children with burns of
      greater than 40% of the total body surface area were randomly divided into 2
      groups to receive placebo (n = 10) or rhGH, 0.2 mg/kg per day intramuscularly (n
      = 10). SETTING: Pediatric burn hospital. MAIN OUTCOME MEASURE: Serum TNF-alpha
      levels by enzyme-linked immunoassay at baseline (day 0) and at 21 and 42 days
      after injury. For statistical analysis, we used the Kruskal-Wallis and Friedman
      tests. RESULTS: No significant differences in age (mean +/- SD, 6.2+/-1.6 vs
      5.0+/-1.2 years) or percentage of total body surface area burn (mean +/- SD,
      65.1%+/-8.2% vs 57.1%+/-5.2%) could be shown between the groups given rhGH and
      placebo. Baseline TNF-alpha levels were elevated from reference values in both
      groups. Twenty-one and 42 days after rhGH administration, serum TNF-alpha levels
      were significantly decreased from those at baseline (P<.05). No significant
      decrease in TNF-alpha levels was observed in the placebo group (P = .5).
      CONCLUSIONS: Recombinant human growth hormone significantly lowers serum TNF
      alpha levels after burn injury. This is consistent with the beneficial effect
      that rhGH has on the acute-phase response.

PMID- 10088570
TI  - Enteral nutrition prevents bacterial translocation but does not improve survival
      during acute pancreatitis.
AB  - OBJECTIVE: To evaluate the effect of enteral nutrition (EN) in attenuating
      bacterial and/or endotoxin translocation, maintaining immune responsiveness, and
      improving outcome in early acute pancreatitis (AP) in Wistar male rats. DESIGN:
      Acute pancreatitis was induced in rats receiving total parenteral nutrition (TPN)
      (AP/TPN group) (n=34) and EN (AP/EN group) (n=35) by pressure injection of 1%
      deoxycholate into the biliopancreatic duct (0.6 mg/kg of body weight). Rats in
      the sham/TPN and sham/EN groups (n=10 each) underwent laparotomy without
      induction of AP. Catheters for TPN and EN were placed into the external jugular
      vein and jejunum, respectively. Rats were infused with Ringer lactate solution
      for 48 hours followed by TPN in the AP/TPN and sham/TPN groups, and EN in the
      AP/EN and sham/EN groups until day 7. The fluid volume and energy (calories)
      intake were similar in all groups. SETTING: Medical school research laboratory.
      MAIN OUTCOME MEASURES: Survival, blood endotoxin level, villus height, 5-bromo-2'
      deoxyuridine (BrdU) uptake in the jejunum and ileum, bacterial culture of
      mesenteric lymph nodes, and CD4/CD8 ratio of T cells in mesenteric lymph nodes,
      spleen, and peripheral blood. RESULTS: There was no difference in survival and
      pancreatic healing between the AP/TPN and AP/EN groups. Colony-forming units of
      the mesenteric lymph nodes and the endotoxin level were significantly lower in
      the AP/EN group than in the AP/TPN group (P<.05). Villus height and BrdU intake
      was significantly higher in the AP/EN group than in the AP/TPN group (P<.05). The
      CD4/CD8 ratio of T cells in spleen and peripheral blood was higher in the AP/EN
      group than in the AP/TPN group (P<.05), whereas there was no difference in
      mesenteric lymph nodes. CONCLUSIONS: Jejunal administration of EN is well
      tolerated in early AP, maintains immune responsiveness and gut integrity, and
      reduces bacterial and/or endotoxin translocation. However, compared with TPN, EN
      does not improve outcome. These results suggest that factors other than bacterial
      and/or endotoxin translocation may be responsible for mortality in this rat model
      of early AP. However, additional studies of both early bacterial and/or endotoxin
      translocation and late assessment of outcome are indicated.

PMID- 10088571
TI  - Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction.
AB  - OBJECTIVES: To examine whether the lung releases nitric oxide (NO) in response to
      thromboxane A2 and to examine the local release of NO as a protective
      compensatory mechanism by which the lung responds to the proinflammatory and
      vasoactive effects of thromboxane A2. DESIGN: The lungs of anesthetized Sprague
      Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an
      inhibitor of NO synthase (nitroglycerinenitro-L-arginine methyl ester [L-NAME])
      (10(-4) mol/L), an NO donor (sodium nitroprusside) (10(-8) mol/L), or perfusate
      alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy
      11alpha, 9alpha-epoxymethanoprostaglandin F2alpha(U-46619) (7.1 X 10(-8) mol/L)
      was added to the perfusate. Fifteen minutes later, the capillary filtration
      coefficient, pulmonary arterial pressure, and vascular resistance were measured.
      Pulmonary NO release was assessed by quantitating the release of cyclic guanosine
      monophosphate into the perfusate. RESULTS: The capillary filtration coefficient
      of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused
      with buffer alone (P<.05). The addition of sodium nitroprusside reduced the
      increase in capillary filtration coefficient associated with U-46619 by 50%
      (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused
      lung caused a 3.0+/-0.4 mm Hg increase in pulmonary artery pressure (P<.01) with
      a corresponding rise in total vascular resistance (P<.05). This effect was
      exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05).
      Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic
      guanosine monophosphate levels within the perfusate. CONCLUSION: These data are
      consistent with the hypothesis that NO release may be an important protective
      mechanism by which the lung responds to thromboxane A2.

PMID- 10088572
TI  - A refined approach to the repair of postcholecystectomy bile duct strictures.
AB  - OBJECTIVE: To assess the results of a refined approach to repair of
      postcholecystectomy bile duct strictures. DESIGN: An 11-year retrospective review
      of patients who had surgical repair of bile duct strictures developing late after
      cholecystectomy. SETTING: A major university teaching hospital in France.
      PATIENTS AND INTERVENTIONS: During an 11-year period from 1987 to 1997, 22
      patients (mean [+/-SD] age, 55+/-15 years) were operated on for bile duct
      strictures after cholecystectomy (11 after laparoscopic surgery and 11 after open
      surgery). Thirteen (59%) of the 22 patients had previous repair. Most patients
      had episodic cholangitis (14 patients [64%]) and biochemical evidence of
      cholestasis (20 patients [91%]). There were 5 Bismuth type 1 strictures; 4, type
      2; 7, type 3; 5, type 4; and 1, type 5. The average (+/-SD) time from initial
      surgery to repair was 6.3+/-9.6 years. Intraoperative cholangiography was used to
      plan the repair in 18 patients (82%). Fifteen patients (68%) were repaired with
      high Hepp-Couinaud hepaticojejunostomies. The last 4 patients had the hilum
      exteriorized by the posterior approach to improve access. RESULTS: There was 1
      intraoperative complication (bleeding) and 4 postoperative complications (biloma,
      fistula, and 2 cholangitis). There were no deaths; mean (+/-SD) length of stay
      was 12.8+/-5.8 days; and mean (+/-SD) follow-up was 4.8+/-3.3 years (range, 1
      10.7 years). Three patients were reoperated on, 1 with an obstructed Roux-en-Y
      limb and the 2 others for incisional hernias. Eighteen patients remain well, 3
      had sporadic recurrent cholangitis after surgery that resolved spontaneously, and
      1 patient remains unwell requiring antibiotics to control cholangitis.
      CONCLUSIONS: Hepp-Couinaud hepaticojejunostomy without stenting remains a
      reliable repair of postcholecystectomy strictures. Intraoperative cholangiography
      and exteriorizing the hilum by the posterior approach are useful adjuncts to this
      technique.

PMID- 10088573
TI  - Hyperthermic isolated limb perfusion with tumor necrosis factor alpha, interferon
      gamma, and melphalan for locally advanced nonmelanoma skin tumors of the
      extremities: a multicenter study.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis
      factor alpha (TNF-alpha), interferon gamma, and melphalan has proved to be useful
      in the treatment of recurrent malignant melanoma and of locally advanced soft
      tissue sarcomas of the extremities. OBJECTIVE: To determine whether this modality
      is also effective in the treatment of locally advanced nonmelanoma skin tumors of
      the extremities. PATIENTS AND METHODS: Fifteen patients with locally advanced
      primary, recurrent, or metastatic skin tumors of the extremities (12 with
      squamous cell carcinoma and 3 with Merkel cell carcinoma) underwent HILP with TNF
      alpha, interferon gamma, and melphalan. Six tumors were localized in the upper
      extremity (40%), and 9 in the lower extremity (60%). Treatment-related
      complications, limb salvage rate, local recurrence, and regional and distant
      metastases were scored during a median follow-up of 20 months. RESULTS: After
      HILP, 9 patients (60%) showed a complete response (with histopathological
      confirmation). Four patients (27%) showed a partial response (with
      histopathological confirmation in 1 patient), and 2 patients (13%) showed no
      change (with histopathological confirmation in 1 patient and with clinical
      evidence in 1 patient). Two patients (13%) showed treatment-related
      complications. The limb salvage was achieved in 12 patients (80%), and the local
      recurrences developed in 4 patients (27%). During follow-up, regional lymph node
      metastases were observed in 2 patients (13%) and distant metastases in 2 patients
      (13%). CONCLUSION: Based on our results, HILP with TNF-alpha, interferon gamma,
      and melphalan should be considered as a limb-saving treatment modality in
      patients with locally advanced nonmelanoma skin tumors of the extremities who
      would otherwise be candidates for ablative surgery.

PMID- 10088574
TI  - Minicholecystectomy: a safe, cost-effective day surgery procedure.
AB  - OBJECTIVE: To document effectiveness of minicholecystectomy as a safe, cost
      effective day surgery procedure with rapid return to work. DESIGN: Review of
      medical records. SETTING: Small community hospital. PATIENTS: A total of 1207
      patients who underwent minicholecystectomies from January 1, 1986, through
      December 31, 1997. INTERVENTION: Minicholecystectomy. MAIN OUTCOME MEASURES:
      Complications, length of hospital stay, cost, and time until return to work.
      RESULTS: Of the 1207 patients who underwent minicholecystectomy, 74% were
      admitted for day surgery, 88% of whom were discharged in less than 12 hours, 9.3%
      in 24 hours or less, and 1.7% in greater than 24 hours; 0.3% were readmitted
      within 2 weeks. The complication rate was 0.2%; 2 cases required laparotomy, with
      no common duct injuries. The cost of the procedure was S435; the average time it
      took working patients to return to work was 11.4 days. CONCLUSIONS:
      Minicholecystectomy is a safe, inexpensive day surgery method of cholecystectomy
      with minimal time off work after surgery.

PMID- 10088575
TI  - Recurrent pancreatitis in Gardner variant familial polyposis: etiology,
      diagnostic approach, and interventional results.
AB  - HYPOTHESIS: Pancreatitis arising from an obstructing ampullary neoplasm in
      patients with Gardner variant familial polyposis is an infrequently described
      clinical entity. We reviewed all patients with Gardner variant polyposis
      presenting with pancreatitis during a 12-year period in our institution, hoping
      to better define etiology and the appropriate diagnostic and interventional
      approach. METHODS: A retrospective record review (1986-1998) defined patient
      demographics, presenting features, initial and subsequent endoscopic retrograde
      cholangiopancreatography (ERCP) findings, subsequent treatments, and both
      immediate and long-term outcomes. Particular consideration was given to initial
      post-ERCP diagnosis and to endoscopic interventions undertaken at that time. We
      also looked at those patients who eventually required surgical intervention after
      long-term failure of medical and endoscopic therapy, the indications for surgery,
      final pathological characteristics, and follow-up results. RESULTS: Eight
      patients (6 women and 2 men), with a mean age of 42 years at initial
      presentation, were found. Each patient was known to have Gardner variant familial
      polyposis at the time of the initial bout of pancreatitis. All had undergone
      prior colectomy and 4 of 8 had undergone prior cholecystectomy. None were known
      to be taking medications or ingesting pancreatoxic substances. Five of 8 patients
      had obstructing focal or diffuse adenomatous disease involving the ampulla. Two
      of 8 patients had pancreatitis attributed to other causes (divisum, stones) and a
      single patient had no clear etiology. Three of 5 patients with ampullary
      adenomatous disease underwent pancreaticoduodenectomy for recurrent adenomatous
      encroachment and ampullary stenosis, despite repetitive snare resection and
      papillotomy. All of these patients had ampullary and other duodenal adenomas, and
      none had malignant disease. CONCLUSIONS: Patients presenting with pancreatitis in
      the setting of Gardner variant familial polyposis will frequently have an
      obstructing ampullary neoplasm, although additional etiologies should be sought.
      Initial endoscopic therapy affords transient relief but may not be definitive.
      The abnormal scarring and fibrosis (keloid formation, desmoid reaction) that
      characterize this disease likely play a large role in endoscopic or subsequent
      surgical failure. A significant number of these patients will go on to require
      surgical referral and intervention.

PMID- 10088576
TI  - Reoperation for severe pancreatitis: a 10-year experience in a tertiary care
      center.
AB  - OBJECTIVES: To analyze the specific problems encountered in treating patients
      previously operated on for necrotizing pancreatitis and to determine the benefit
      of such a complex and demanding procedure. DESIGN AND SETTING: Review of a case
      series in an academic tertiary care referral center. PATIENTS: Forty-four
      consecutive patients referred and reoperated on in 10 years. INTERVENTIONS:
      Reiterative laparotomy with complete debridement of all necrotic sites, followed
      by Mikulicz packing. Mikulicz packs were replaced by removable drains allowing
      both local prolonged lavage and open drainage of large solid necrotic debris.
      Enteral nutrition was performed through a feeding jejunostomy. Associated
      gastrointestinal tract lesions were simultaneously treated. MAIN OUTCOME
      MEASURES: Operative findings, bacteriological status of necrosis, in-hospital
      mortality, length of hospitalization, and surgical complications and their
      management. RESULTS: Necrosis was infected in 36 (82%) of the 44 cases and
      associated gastrointestinal tract lesions were found in 20 (45%) of these
      patients. Mortality was 23%, and was significantly (P = .03) related to the
      preoperative clinical status. Surgical complications occurred in 31 (70%) of the
      44 patients necessitating surgical treatment in 18 (41%) of these patients. Mean
      (+/- SD) stay in the intensive care unit was 66+/-8 days for survivors.
      CONCLUSION: This complex and demanding surgical procedure is worthwhile, yielding
      mortality rates comparable to those observed in de novo severe necrotizing
      pancreatitis.

PMID- 10088577
TI  - A medical student's meeting with two giants.

PMID- 10088578
TI  - Surgery in the Philippines.
AB  - The Philippines is an archipelago of about 7000 islands, with an area about the
      size of England, situated just above the equator in Southeast Asia. It has a
      population of 70 million. The Philippines has had extensive commercial and social
      contact with Asian neighbors, specifically the Chinese, even before the 377 years
      of Spanish colonization from 1521 to 1898 and the 48 years of American rule from
      1898 to 1946. More than 80% of Filipinos are Catholics; the rest are Muslims and
      Protestants of various denominations, including those who belong to Filipino
      church groups. Infectious diseases such as tuberculosis, amoebiasis, typhoid
      fever, and malaria are still prevalent, and arteriosclerosis, cancer, and stroke
      are common and on the rise.

PMID- 10088579
TI  - Management of acute mesenteric ischemia.
AB  - Acute mesenteric ischemia is a serious illness requiring prompt surgical
      attention. The clinical presentation, diagnostic strategy, and management of this
      disease are reviewed. Options for revascularization are briefly outlined.

PMID- 10088580
TI  - A Treatise on the malformation, injuries, and diseases of the rectum and anus:
      America's first textbook on colorectal surgery.

PMID- 10088581
TI  - Insertional activity.

PMID- 10088582
TI  - Clinical presentations, medical complications, and functional outcomes of
      individuals with gunshot wound-induced spinal cord injury.
AB  - Gunshot wounds are currently the second leading cause of spinal cord injury in
      the United States, and coexisting injuries or complications accompanying
      penetrating wounds often increase patient morbidity. A review of 217 traumatic
      spinal cord injury rehabilitation admissions to a tertiary care hospital during a
      5-yr period revealed 49 individuals (23%) with gunshot wound-induced spinal cord
      injury. A single bullet entry site was seen in 54%, whereas 17% had greater than
      3 sites of entry. Common (>25%) sites of bullet entry included the back, abdomen,
      neck, and chest. Common gunshot wound-related medical complications included pain
      (54%), infections (40%), pneumothorax (24%), nonspinal fractures (22%), colonic
      perforation (17%), cerebrospinal fluid leak (10%), and retroperitoneal hematoma
      (10%). When compared with nonviolence-related traumatic spinal cord injury (motor
      vehicle accidents and falls), patients with gunshot wound-induced spinal cord
      injury were significantly more frequently (P < 0.01) younger, non-Caucasian,
      unmarried, and unemployed. Injury characteristics revealed significantly (P <
      0.01) more paraplegia and complete spinal cord injury within the gunshot wound
      induced spinal cord injury group. Gunshot wound-induced spinal cord injury and
      nonviolent traumatic spinal cord injury groups had similar lengths of stay,
      Functional Independence Measure scores, and discharge to home rates. This article
      adds to the growing body of literature examining clinical, medical, and
      functional outcome characteristics of individuals with spinal cord injury
      secondary to violence-related cause.

PMID- 10088583
TI  - External stimuli in the form of vibratory massage after heart or lung
      transplantation.
AB  - Manual vibratory massage is part of the preventive physiotherapeutic activities
      performed in intensive care units. The vibratory massage can be performed
      manually or as electrovibratory massage. The manual massage is a fast rhythmical
      vibration performed by the arm and shoulder muscles of the masseur and
      transferred to the patient's thorax by the hand. The hand of the masseur has to
      achieve a tremor with a frequency of 8 to 11 tremors/s. The aim of the pilot
      study was to examine the influence of manual vibratory massage on the pulmonary
      function of postoperative patients who were receiving mechanical ventilation,
      with special interest being focused on pulmonary ventilation and perfusion and
      cerebral blood flow velocity. Manual vibratory massage was performed
      postoperatively in the intensive care unit on eight patients: three patients had
      undergone heart transplantation, three had undergone lung transplantation, and
      two had undergone coronary artery bypass grafting (mean age, 53.6+/-8 yr). With
      the aid of continuous monitoring, we examined the changes of the respiration
      parameters and the cerebral blood flow velocity (measured by transcranial Doppler
      sonography). The vibratory massage was performed with a frequency of 8 to 10
      vibrations/s for 15 min, 7.5 min on each side of the thorax, starting from the
      lower costal arch and progressing to the upper thoracic aperture. For 10 min
      before, during, and 10 min after the massage, the parameters of peripheral oxygen
      saturation, central venous pressure, mean arterial pressure, heart rate, lung
      resistance and compliance, tidal volume, respiration rate, and cerebral blood
      flow velocity were recorded at 2-min intervals. Moreover, before and after
      vibratory massage, arterial blood gases were determined. In four of the eight
      patients, it was possible to determine pulmonary arterial pressure, pulmonary
      capillary wedge pressure, as well as pulmonary vascular resistance. During the
      vibratory massage, we could prove a significant increase of the mean tidal volume
      by 30% (P = 0.008). The percutaneous oxygen saturation significantly increased
      also, from 92 to 93.6% (P = 0.002). Central venous pressure significantly
      decreased by 11% (P = 0.04), and pulmonary vessel resistance was reduced by 18.3%
      (P = 0.001). The pulmonary resistance decreased from 10.5 to 9.2 H2O/l/s (P <
      0.05) by the end of the observation period. Cerebral blood flow velocity showed
      no significant change. Vibratory massage seems to improve pulmonary mechanism and
      perfusion, thus, reducing ventilation perfusion mismatch and increasing oxygen
      saturation.

PMID- 10088584
TI  - Intravenous dipyridamole thallium imaging V combined arm-leg cycle stress testing
      of patients unable to exercise on the treadmill.
AB  - Rehabilitation patients who will undergo noncardiac surgery or strenuous
      rehabilitation programs often cannot exercise to greater than 85% of predicted
      maximal heart rate as required for valid treadmill testing. Because many patients
      have known or suspected coronary artery disease, greatly increasing their risk
      for a cardiac event, dipyridamole thallium scans are usually performed, despite a
      cost of approximately $1400, patient radiation exposure, and the need for a gamma
      camera. Instead, arm-leg cycle stress testing can be continued to an
      appropriately high heart rate, is done in the physician's office with an
      electrocardiograph machine and a blood pressure cuff, and costs $250. This study
      describes nine patients who had both dipyridamole thallium scans and arm-leg
      cycle ergometry. Four awaited peripheral vascular surgery, one needed bilateral
      knee replacements, one was an amputee, and three had claudication. Six had
      documented and three had suspected coronary disease. RESULTS: In eight of nine
      patients, the electrocardiograms during both dipyridamole thallium imaging and
      ergometry were in agreement as to the presence or absence of ischemia (kappa
      statistic, 0.7273; P = 0.0117). In seven of nine patients, thallium images and
      ergometry agreed (78% concurrence). To achieve 90% agreement between dipyridamole
      thallium scans and cycle results, however, 68 patients would have to be studied.
      CONCLUSION: In this preliminary study, arm-leg ergometry was feasible in all
      patients and seemed cost-effective and useful for detecting myocardial ischemia.
      Clinically, if the ergometry were inconclusive, dipyridamole thallium scans could
      be performed subsequently to obtain the needed information.

PMID- 10088585
TI  - Clinical trial of electrical acupuncture on hemiplegic stroke patients.
AB  - To assess the efficacy of electrical acupuncture in the rehabilitation of
      patients with hemiplegia in stroke, we randomized 128 patients within 2 wk of
      stroke onset to receive either comprehensive rehabilitation plus electrical
      acupuncture (n = 59) or comprehensive rehabilitation only (n = 59). Electrical
      acupuncture was administered by electrical stimulation of acupuncture points
      through adhesive surface electrodes five times per week. Neurological status
      (Brunnstrom's stage) and the Chinese version of the Functional Independence
      Measure were assessed before treatment and at discharge. Patients treated with
      electrical acupuncture had a shorter duration of hospital stay for rehabilitation
      and better neurological and functional outcomes than the control group had, with
      a significant difference in scores for self-care and locomotion (P = 0.02). This
      result did not postulate the previous study that acupuncture therapy for stroke
      patients should depend on needle manual and "de qi" response. We suggest that
      electrical acupuncture through adhesive surface electrodes in conjunction with
      current optimal rehabilitation programs is a convenient and effective therapy for
      stroke patients.

PMID- 10088586
TI  - Analysis of the clinical factors determining natural and maximal gait speeds in
      adults with a stroke.
AB  - The objective of this study was to identify the most important clinical variables
      determining gait speed in persons with stroke. Sixteen chronic stroke subjects
      (mean age, 47.9 (+/-15.6) yr; mean time post-stroke, 43.9 (+/-36.5) mo) able to
      walk independently without a brace participated in the study. The impairments in
      motor function, sensation of the paretic lower limb, and balance were evaluated
      with the Fugl-Meyer Assessment. A spasticity index was used to assess the muscle
      tone of the plantarflexors. The maximal strengths in plantarflexion and hip
      flexion were measured with a Biodex dynamometric system. Cinematography and foot
      contact data collected on the paretic side were used to determine the comfortable
      and maximal gait speeds. The level of association between gait speeds and the
      clinical variables were first examined with Pearson's correlation coefficients
      and, then, with multiple linear regression analyses using the stepwise method.
      Results revealed that the motor function of the lower limb, balance, and hip
      flexion strength were significantly related to comfortable and maximal gait
      speeds (0.5 < r < 0.88; P < 0.05). For the comfortable gait speed, the regression
      analysis selected only the hip flexor strength as a significant variable (R2 =
      0.69). For maximal gait speed, the variables retained were hip flexor strength,
      sensation at the lower limb, and plantarflexor strength (R2 = 0.85). The present
      results suggest that strength and sensation at the lower limb are important
      factors to consider in determining the gait capacity of chronic stroke subjects.

PMID- 10088587
TI  - Wheelchair propulsion: descriptive comparison of hemiplegic and two-hand patterns
      during selected activities.
AB  - Most manual wheelchair users with hemiplegia use both the unaffected arm and leg
      to propel their wheelchairs. The objective of this study was to compare the
      wheelchair propulsion of subjects using the hemiplegic pattern (one arm and one
      leg) with subjects using two hands. In a case-controlled study in a kinesiologic
      laboratory, nine wheelchair users who used the hemiplegic pattern were compared
      with nine matched controls who used the two-handed pattern. Participants were
      tested for propelling and stopping the wheelchair, forward and backward, on a
      level surface and on a 5 degree incline. Video recording was used to assess
      deviation from the midline, foot slippage, the number of propulsive cycles, and
      the propelling velocity. Also, on the 5 degree incline, we noted the need for
      support when unlocking the wheel locks, instances of grabbing the side rail, or
      rollback between propulsions. The participants using the hemiplegic pattern when
      propelling up the incline deviated more to the hemiparetic side (P < 0.05), used
      more propulsive cycles per unit of distance (P < 0.01), were slower (P < 0.001),
      and used the side rail more often (P < 0.05). When propelling forward on level
      ground, the participants using the hemiplegic pattern were slower (P < 0.005).
      When stopping after moving backward down the incline, they were more likely to
      deviate to the unaffected side (P < 0.01). In conclusion, wheelchair users who
      use the hemiplegic pattern experience more difficulties than those using two
      hands, some of which may be amenable to improvements in wheelchair prescription
      and training.

PMID- 10088588
TI  - Automobile driving performance of brain-injured patients with visual field
      defects.
AB  - The purpose of this study was to examine whether patients with visual field
      defects resulting from cerebral injury are handicapped in their driving ability,
      because visual field loss as assessed in standard perimetry is often the basis
      for withdrawal of a person's driving license. Driving performance was tested on a
      driving simulator to obtain standardized results and for safety reasons. The
      visual field was assessed both with standard automated perimetry and computer
      based, high-resolution, qualitative perimetry. We investigated nine patients with
      purely cerebral field defects (mostly homonymous binocular defects) who had no
      further neuropsychological or ophthalmological deficits. Their performance
      (driving speed, reaction time, and driving error rate) was compared with that of
      a control group of ten subjects. We found no differences in any of the tested
      parameters between the visually impaired subjects and the normal participants.
      This suggests that individuals with visual field defects, including those who
      suffer from homonymous hemianopia, may perform as adequately as normal
      individuals in realistic driving scenarios. The perimetrically assessed visual
      field may, thus, be of limited value for the prediction of driving safety, and we
      conclude that patients who have field defects should not summarily be denied a
      driving license.

PMID- 10088589
TI  - Are stroke patients discharged sooner if in-patient rehabilitation services are
      provided seven v six days per week?
AB  - A comparison was made of 113 consecutive patients who suffered a cerebrovascular
      accident and were hospitalized at a rehabilitation inpatient unit by dividing
      them into two groups: one group received the traditional 6-day/wk treatment
      regimen, and another group received treatment during the entire week (7 days/wk).
      When the patients were asked whether they had a preference (which did not affect
      their group assignment), 82% preferred a 6-day/wk program and 18% preferred a 7
      day/wk program. The length of inpatient stay for the 57 patients enrolled in the
      6-day/wk program was 20.14 days; for the 56 patients enrolled in the 7-day/wk
      program, the average length of stay was 20.11 days. This represents no
      significant difference. The functional recoveries were evaluated in areas that
      can affect length of stay, including dressing, bladder control, ambulation, and
      problem-solving. Both groups demonstrated significant gains in each domain when
      the intake and discharge ratings were compared. However, these gains were not
      significantly different when the 6- and 7-day/wk groups were compared. The
      results of the study contained herein, therefore, suggest that a 6-day/wk program
      for patients who have suffered a cardiovascular accident is just as effective as
      a 7-day/wk program.

PMID- 10088590
TI  - Relationship between stride length and walking rate in gait training for
      hemiparetic stroke patients.
AB  - Sixty-three male hemiparetic patients in the recovery stage were examined to
      investigate the relationship between stride length and walking rate during
      computer-assisted gait training during a period of 4 wk. The maximum walking
      speed for 10 m was significantly increased from 32.3 to 53.2 m/min on average,
      and the stride length and walking rate also increased. However, the ratio of
      stride length to walking rate did not change significantly in 4 wk, with the mean
      value being 0.0068 m/steps/min, approximately one-half that of healthy adults
      based on data from previous reports. The ratio of stride length to walking rate
      for hemiplegic gait was invariant during the 4 wk of computer-assisted gait
      training, which is also true at different speeds for healthy adults. These
      results indicate that the maximum walking speed was significantly improved, with
      an invariant relationship between stride length and walking rate, and suggest
      that the ratio could be used as an index for gait training.

PMID- 10088591
TI  - Sciatic neuropathy secondary to a uterine fibroid: a case report.
AB  - Lesions of the sciatic nerve outside the pelvis have been well described. Lesions
      within the pelvis, however, are far less common. We report the case of a 55-yr
      old woman with a history of chronic low back pain who presented with progressive
      right buttock and posterolateral right lower limb pain associated with right foot
      numbness and tingling. She denied any associated low back or left lower limb
      pain. The patient was initially treated for a probable right lumbosacral
      radiculopathy, without improvement. A subsequent magnetic resonance image of the
      lumbosacral spine revealed multilevel disc degeneration at L3-4 through L5-S1,
      without disc herniation or canal stenosis. A magnetic resonance image of the
      pelvis revealed a markedly enlarged uterus, with a large pedunculated myoma
      impinging on the right sciatic foramen. The patient underwent a subtotal
      abdominal hysterectomy, with resolution of her right lower limb pain. This case
      illustrates the importance of considering intrapelvic causes of sciatic
      neuropathy. To our knowledge, this is the first reported case of sciatic
      neuropathy secondary to a uterine fibroid.

PMID- 10088592
TI  - Total hip disarticulation prosthesis with suction socket: report of two cases.
AB  - A majority of hip disarticulations are performed in young people, with malignancy
      being the most common cause. The exoskeletal Canadian Hip Disarticulation
      prosthesis had been widely used as a standard total hip disarticulation
      prosthesis until recently when an endoskeletal modular version became the
      prosthesis of choice. However, the "basket-shaped" socket provided by the
      standard total hip disarticulation prostheses has been a source of discomfort and
      a reason for prosthetic rejection by many patients. This report concerns two
      patients with true lower limb disarticulation at the hip joint. Both of the
      patients failed to adapt to the standard total hip disarticulation prosthesis but
      successfully used a new total contact suction socket design. This new prosthesis
      provided improved suspension, better patient compliance, and enhanced prosthetic
      acceptance and mobility.

PMID- 10088593
TI  - Alternate four-point sweep-through gait--a technique for patients with combined
      neuromuscular and visual impairments: case reports.
AB  - This article reports on two patients with combined neuromuscular and visual
      impairments who used a modification of the classic alternate four-point crutch
      gait, which allowed them to simultaneously explore the upcoming environment for
      obstacles or change in terrain while maintaining sufficient support for their
      lower limbs. The technique should be useful for patients with diabetic
      neuropathy/retinopathy combinations, multiple sclerosis with optic neuritis, and
      neurosarcoidosis and in elderly patients with multiple disabilities.

PMID- 10088594
TI  - Failure to adhere to rehabilitation principles--painful lessons learned: a
      commentary.

PMID- 10088595
TI  - Case studies, single-subject research, and N of 1 randomized trials: comparisons
      and contrasts.
AB  - Case studies, single-subject research designs, and N of 1 randomized clinical
      trials are methods of scientific inquiry applied to an individual or small group
      of individuals. A case study is a form of descriptive research that seeks to
      identify explanatory patterns for phenomena and generates hypotheses for future
      research. Single-subject research designs provide a quasi-experimental approach
      to investigating causal relationships between independent and dependent
      variables. They are characterized by repeated measures of an observable and
      clinically relevant target behavior throughout at least one pretreatment
      (baseline) and intervention phase. The N of 1 clinical trial is similar to the
      single-subject research design through its use of repeated measures over time but
      also borrows principles from the conduct of large, randomized controlled trials.
      Typically, the N of 1 trial compares a therapeutic procedure with placebo or
      compares two treatments by administering the two conditions in a predetermined
      random order. Neither the subject nor the clinician is aware of the treatment
      condition in any given period of time. All three approaches are relatively easy
      to integrate into clinical practice and are useful for documenting individualized
      outcomes and providing evidence in support of rehabilitation interventions.

PMID- 10088596
TI  - The cell biology of leukocyte-mediated proteolysis.
AB  - Leukocyte-derived proteinases have the capacity to degrade every component of the
      extracellular matrix, and thereby play fundamental roles in physiological
      processes. However, if the activity of these proteinases is uncontrolled or
      dysregulated, they have the capacity to contribute to tissue injury that
      potentially affects every organ in the body. Although there is a substantial
      literature on structure and activity of these proteinases when they are free in
      solution, until recently there has been little information about the cell biology
      of proteinases and their inhibitors. Recent studies, however, have identified
      several mechanisms by which inflammatory cells can degrade extracellular proteins
      in a milieu that contains high-affinity proteinase inhibitors.

PMID- 10088597
TI  - The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor
      CD38.
AB  - Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of
      expression in leukocytes, although evidence is accumulating of its quite
      widespread expression in cells of nonvascular origin. CD38 is a member of a
      nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes
      whose substrate is NAD, a coenzyme ubiquitously distributed in nature.
      Functionally, CD38 is an eclectic molecule with the ability not only to catalyze
      but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan,
      and to other ligands. Interaction with CD38 on various leukocyte subpopulations
      has profound though diverse consequences on their life-span, but these effects
      seem to be independent of the enzymatic activity of the molecule. CD38 challenges
      our expectations of a surface molecule and we must sift through its many guises
      to unmask its true nature.

PMID- 10088598
TI  - Macrophages interact with enriched populations of distinct T lymphocyte subsets
      for the induction of severe destructive Lyme arthritis.
AB  - Severe destructive Lyme arthritis was detected in the hind paws of hamsters
      infused with enriched populations of either CD4+ or CD4- T lymphocytes along with
      macrophages exposed in vitro to formalin-inactivated Borrelia burgdorferi and
      then infected with the Lyme spirochete. Swelling was detected 4 days after
      infection, increased rapidly, peaked on day 8 of infection, and gradually
      decreased. Similarly, severe destructive arthritis was induced in hamsters
      infused with enriched populations of unfractionated T lymphocytes and macrophages
      exposed to spirochetes after infection with B. burgdorferi. Histopathological
      examination affirmed that hamsters infused with CD4+, CD4-, or unfractionated T
      lymphocytes and macrophages exposed to B. burgdorferi-induced arthritis. In
      addition, macrophages exposed in vitro to B. burgdorferi demonstrated both
      conventional and coiling phagocytosis, suggesting a mechanism by which CD4+ and
      CD4- T lymphocytes induce arthritis, respectively. These findings demonstrate
      that both CD4+ and CD4- subpopulations of T lymphocytes are capable of
      interacting with macrophages for the induction of severe destructive Lyme
      arthritis.

PMID- 10088599
TI  - Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes by
      hypoxia/reoxygenation.
AB  - Interleukin-8 (IL-8) is an important mediator of neutrophil (PMN) function and
      the type A IL-8 receptor (IL-8RA) mediates these pro-inflammatory signals.
      Hypoxia or hypoxia/reoxygenation (H/R) affects the production of IL-8, but no
      data is available regarding its effect on IL-8RA expression. The purpose of this
      study was to determine the effects of hypoxia and/or H/R on the expression of IL
      8RA in PMN. We demonstrated that IL-8RA mRNA levels were similar under normoxic
      and hypoxic conditions but H/R resulted in a significant reduction in mRNA
      expression between 30 and 60 min. IL-8RA protein also decreased with
      reoxygenation of whole blood, which was altered by the addition of specific
      antioxidants. Therefore, H/R appears to attenuate the effect of IL-8 by down
      regulating IL-8RA in PMN. These data show that changes in oxygen tension within
      the wound site not only affect the expression of inflammatory cytokines, but also
      control their actions by regulating their receptors.

PMID- 10088600
TI  - Leukocyte subsets and neutrophil function after short-term spaceflight.
AB  - Changes in leukocyte subpopulations and function after spaceflight have been
      observed but the mechanisms underlying these changes are not well defined. This
      study investigated the effects of short-term spaceflight (8-15 days) on
      circulating leukocyte subsets, stress hormones, immunoglobulin levels, and
      neutrophil function. At landing, a 1.5-fold increase in neutrophils was observed
      compared with preflight values; lymphocytes were slightly decreased, whereas the
      results were variable for monocytes. No significant changes were observed in
      plasma levels of immunoglobulins, cortisol, or adrenocorticotropic hormone. In
      contrast, urinary epinephrine, norepinephrine, and cortisol were significantly
      elevated at landing. Band neutrophils were observed in 9 of 16 astronauts.
      Neutrophil chemotactic assays showed a 10-fold decrease in the optimal dose
      response after landing. Neutrophil adhesion to endothelial cells was increased
      both before and after spaceflight. At landing, the expression of MAC-1 was
      significantly decreased while L-selectin was significantly increased. These
      functional alterations may be of clinical significance on long-duration space
      missions.

PMID- 10088601
TI  - T cell independence of bleomycin-induced pulmonary fibrosis.
AB  - The role of T cells and cytokines in bleomycin (BLM)-induced fibrosis was
      evaluated in susceptible and resistant strains of normal and SCID mice. Histology
      and hydroxyproline analysis showed that BLM induced pulmonary fibrosis in C57BL/6
      and (C57BL/6 x BALB/c)F1 mice, whereas BALB/c mice were resistant to the disease.
      To test whether lymphocytes were required for the induction of BLM-induced
      pulmonary fibrosis, SCID mice were injected intratracheally with BLM and
      evaluated for the development of pulmonary inflammation and fibrosis. Similar
      morphological changes and increases in hydroxyproline were observed in both
      C57BL/6 SCID and (C57BL/6 x CB.17)F1 SCID animals compared to those seen in wild
      type C57BL/6 and (C57BL/6 x BALB/c)F1 mice. In contrast, CB.17 SCID mice, which
      are genetically similar to BALB/c mice, were resistant to disease induction.
      Analysis of the cellular infiltrate in BLM-treated C57Bl/6 SCID mice confirmed a
      lack of T cells in the lungs of SCID mice and demonstrated a pronounced
      accumulation of eosinophils in areas of developing pulmonary fibrosis. NK cells
      were significantly elevated in untreated SCID mice and did not increase further
      after BLM treatment. Analysis of selected cytokines 1 day after initiation of BLM
      induced pulmonary fibrosis indicated that the levels of TNF-alpha and IFN-gamma
      appeared to segregate with fibrosis in both the SCID and wild-type mice. The data
      demonstrate that T cells are not required for the induction of fibrosis by BLM
      and suggest that responses by non-lymphoid cells may be sufficient for the
      induction of fibrosis.

PMID- 10088602
TI  - Activation of the granule pool of the NADPH oxidase accelerates apoptosis in
      human neutrophils.
AB  - Oxidative stress induces apoptosis in many types of cells, including human
      neutrophils. Our objective was to determine whether reactive oxygen species (ROS)
      produced by activated neutrophils are associated with accelerated apoptosis.
      Exposing neutrophils to ionomycin or phorbol myristate acetate (PMA) induced
      intracellular H2O2 production and rapid onset of apoptosis, measured as condensed
      chromatin, cellular shrinkage, and DNA fragmentation. Neutrophils activated with
      formyl-methionyl-leucyl-phenylalanine (fMLP) generated mainly extracellular H2O2
      and did not undergo apoptosis. Exogenously added H2O2, together with the catalase
      blocker sodium azide, induced apoptosis to the same extent and with similar
      kinetics as PMA and ionomycin. Adenosine inhibited ionomycin-induced
      intracellular H2O2 production and apoptosis. Neither PMA nor ionomycin caused
      apoptosis in dimethyl sulfoxide-differentiated HL-60 cells, which are incapable
      of intracellular H2O2 production, whereas H2O2 induced apoptosis more efficiently
      in these cells than in neutrophils. We propose that activated neutrophils use
      intracellularly formed H2O2 to commit suicide.

PMID- 10088603
TI  - Granulocyte-macrophage colony-stimulating factor modulates tapasin expression in
      human neutrophils.
AB  - Differential display-polymerase chain reaction (DD-PCR) was used to evaluate
      changes in mRNA expression of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) treated human neutrophils to better understand how this cytokine affects
      the functions of neutrophils at the molecular level. Although a variety of cDNA
      fragments were identified as modulated by GM-CSF with the use of DD-PCR, one
      fragment in particular, NGS-17 (neutrophil GM-CSF-stimulated fragment #17), was
      characterized. The NGS-17 fragment hybridized to a 3.8-kh mRNA that encodes for a
      protein of a predicted molecular mass of 47.6 kDa. After cloning and sequencing,
      this gene was found to code for the recently sequenced tapasin or TAP-A protein.
      Immunoprecipitation and immunoblotting studies using anti-tapasin antibodies
      showed that tapasin is expressed in neutrophils and is associated with the MHC
      class I-TAP complex. Moreover, tapasin expression was found to be induced by
      dimethyl sulfoxide and by retinoic acid in HL-60 cells. This is the first report
      on the expression of tapasin in human neutrophils. It provides novel information,
      at the molecular level, on how GM-CSF enhances the functions of these cells.

PMID- 10088604
TI  - Disparities in the respiratory burst between human and rat neutrophils.
AB  - The importance of reactive oxygen species (ROS) in neutrophil (PMN)-mediated
      injury to host tissues has been strongly implicated in a number of animal models.
      Peculiarities of the laboratory rat PMN, including an apparent paucity of
      superoxide release, prompted us to examine disparities in the respiratory burst
      between human and rat PMNs. Using isolated PMNs, we examined oxygen consumption,
      superoxide release, nitrate/nitrite release, and dihydrorhodamine (DHR) oxidation
      in response to an array of soluble stimuli. Our findings confirm that intact rat
      PMNs release little superoxide in comparison to human PMNs when primed and
      activated by soluble stimuli. For example, PMA-activated human PMNs released
      superoxide at 10.1 +/- 2.7 times the rate of rat PMNs (P < 0.01). However,
      measurements of oxygen consumption, cell-associated oxidant production (by DHR
      oxidation) and release of superoxide from electroporated cells suggests that rat
      PMNs generate oxidants at rates equivalent to human PMNs but preferentially
      release them in an intracellular compartment. Implications for the study of PMN
      mediated oxidant injury in animal models are discussed.

PMID- 10088605
TI  - Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and
      their precursors.
AB  - Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM;
      approximately 50% of BM cells), in peripheral blood (PB), and in inflammatory
      infiltrates of mice, but also in humans during myeloproliferative disorders. They
      are usually referred to as polymorphonuclear cells (PMN), but we demonstrate that
      they additionally encompass different types of mononuclear (MNC)-like ring cells.
      PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center
      and were sorted among the GR-1high fraction. The MNC-like ring cells belonged to
      the GR-1low fraction. Their nuclei were not segmented and the cytoplasmic center
      of their nuclei was small. They were heterogeneous with one subgroup containing
      monocytes/macrophages according to ultrastructure, immunophenotype (BM8, F4/80,
      CD13, ER-HR3), activity of unspecific esterase, and phagocytosis of Leishmania
      major. A second subgroup contained myeloic precursor cells as they proliferated
      (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of
      peroxidase activity compatible with myelocytes, promyelocytes, or promonocytes. A
      third subgroup of cells had large, sometimes lobulated nuclei, was lineage
      marker(negative/low) (GR-1, Mac-1, B220 etc.), CD38-, but c-kit+ and sca-1+, and
      thus belonged to a close progeny of murine hematopoietic stem cells. In PB, ring
      cells encompassed mainly PMN, but also monocytes and cells with characteristics
      of both the granulocytic and monocytic lineage. Thus, ring cells comprise mature
      and precursor forms of myeloic cells. Their analysis revealed that in mice a
      clear distinction between the granulocytic and monocytic lineage beyond the GM
      CFU stage is not always feasible.

PMID- 10088606
TI  - Lipopolysaccharide can block the potential of monocytes to differentiate into
      dendritic cells.
AB  - We examined whether priming monocytes (MO) with lipopolysaccharide (LPS)
      influenced their further differentiation into either macrophages (Mphi) or
      dendritic cells (DC). LPS-primed MO differentiated into Mphi when cultured
      further with Mphi colony-stimulating factor (M-CSF) but, if cultured then with
      granulocyte/Mphi (GM)-CSF and IL-4 (interleukin-4), only about 30% of the cells
      differentiated into CD1a+ CD14- DC and half became CD1a- CD14+ Mphi. Cytokines
      present during LPS priming could affect subsequent MO differentiation. Relative
      to priming with LPS alone, adding M-CSF to LPS did not modify differentiation of
      MO to Mphi in further culture with M-CSF, nor did it change the way of
      differentiation of MO into DC was altered if culture was later switched to GM
      CSF/IL-4. Using GM-CSF/IL-4 plus LPS upon priming did not modify differentiation
      of MO to Mphi in further culture with M-CSF, as compared to priming with GM
      CSF/IL-4 alone, but it counteracted the effect of LPS on the differentiation of
      MO to DC in further culture with GM-CSF/IL-4: about 75% of cells then became DC.
      Alternatively, despite activation by LPS, mature M-CSF-induced Mphi preserved the
      potential to differentiate into DC on subsequent culture with GM-CSF/IL-4. Thus,
      LPS, a bacterial product known to sustain maturation of MO/Mphi as well as of DC,
      may block the differentiation of MO into DC, except if signal triggering DC
      differentiation is delivered concomitantly, and modulate in this manner the
      induction of adaptive immune responses to infection.

PMID- 10088607
TI  - Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of
      Staphylococcus aureus via phospholipase D activation in human monocytes.
AB  - Among the phagocytic leukocytes, monocytes have the important role of clearing
      out parasitic microorganisms. They accomplish this through production of toxic
      metabolites of oxygen. Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), a peptide that
      stimulates phosphoinositide (PI) hydrolysis in human leukocytes, including
      monocytes, binds to a unique cell surface receptor and stimulates superoxide
      generation, killing of Staphylococcus aureus, and activation of phospholipase D
      (PLD) in human monocytes. Preincubation of the cells with a PI-specific
      phospholipase C (PLC) inhibitor (U-73122), protein kinase C inhibitor
      (GF109203X), or intracellular Ca2+ chelator (BAPTA/AM) before the peptide
      stimulus totally inhibits the peptide-induced PLD activation and superoxide
      generation. On the other hand, tyrosine kinase inhibitor genistein only partially
      inhibits the peptide-induced processes. The peptide-induced bacteria killing
      activity shares regulatory mechanisms for PLD activation with the superoxide
      generation, which is inhibited in the presence of 1-butanol. We suggest that the
      peptide stimulates PLD downstream of PLC activation and PLD activation in turn is
      essential for the peptide-induced immunological functions such as the superoxide
      generation and killing of bacteria by human monocytes.

PMID- 10088608
TI  - Regulation of early peritoneal neutrophil migration by macrophage inflammatory
      protein-2 and mast cells in experimental peritonitis.
AB  - Neutrophil (PMN) migration into the peritoneal cavity in response to fecal
      peritonitis is an important mechanism of host defense against bacterial invasion.
      We show that the murine C-X-C (PMN-specific) chemokine, macrophage inflammatory
      protein-2 (MIP-2), on intraperitoneal injection in mice, causes PMN migration
      into the peritoneum. MIP-2 mRNA and protein were expressed by peritoneal
      leukocytes after cecal ligation and puncture (CLP) in mice and neutralization of
      MIP-2 reduced peritoneal PMN migration. A prerequisite for neutrophil-endothelial
      adhesion and subsequent migration from the circulation is selectin-mediated
      rolling. Pretreatment of mice with an anti-P-selectin antibody before
      intraperitoneal injection of MIP-2 significantly reduced peritoneal PMN
      migration. However, there are no reports that a C-X-C chemokine can up-regulate
      endothelial selectins. We postulated that MIP-2, when injected intraperitoneally,
      interacts with a cell that is known to release factors that up-regulate
      endothelial selectins. A likely candidate is the mast cell, which contains
      histamine and tumor necrosis factor alpha (TNF-alpha), and both of these factors
      induce selectins. Intraperitoneally injected MIP-2 caused an early significant
      increase in peritoneal TNF-alpha, whereas histamine levels were unaffected. In a
      subsequent experiment, mast cell-deficient mice and their normal controls were
      then injected intraperitoneally with MIP-2 or underwent CLP. Significantly fewer
      PMNs migrated into the peritoneal cavity in the mast cell-deficient mice after
      MIP-2 injection or CLP. Thus, our findings indicate that mast cells and MIP-2 are
      necessary for PMN migration into the peritoneum in response to intra-abdominal
      infection, and that MIP-2 appears to facilitate this through an increase in TNF
      alpha release.

PMID- 10088609
TI  - Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF
      or GM-CSF.
AB  - Gene-targeted mice lacking the hemopoietic growth factors, granulocyte colony
      stimulating factor (G-CSF) or granulocyte-macrophage (GM)-CSF, show increased
      susceptibility to infection with the facultative intracellular bacterium,
      Listeria monocytogenes. The resident peritoneal cell populations from G-CSF(-/-)
      and GM-CSF(-/-) mice showed reduced production of the bactericidal molecule
      nitric oxide. Macrophage-mediated tumoricidal activity and phagocytosis of
      Listeria were reduced in G-CSF(-/-), but not in GM-CSF(-/-), mice. In G-CSF(-/-)
      mice, there was an unexpected expansion (from 18% in WT to 38%) of a population
      of cells with morphology intermediate between typical macrophages and typical
      lymphocytes. These cells had some of the features of poorly differentiated
      macrophages, being adherent to plastic but poorly phagocytic, nonspecific
      esterase positive but myeloperoxidase negative. They were largely negative for
      the macrophage marker F4/80 and for Thy1, B220, and Gr1. Their disproportionate
      presence, and the corresponding deficiency in typical macrophages, possibly
      accounts for some of the functional deficiencies observed in G-CSF(-/-) mice.

PMID- 10088610
TI  - LPS down-regulates the expression of chemokine receptor CCR2 in mice and
      abolishes macrophage infiltration in acute inflammation.
AB  - Interactions between chemokines and their specific receptors are important for
      leukocyte trafficking. The CC-chemokine monocyte chemoattractant protein-1 (MCP
      1) and its specific receptor CCR2 are essential in monocytic infiltration and
      have been associated with several inflammatory diseases. It has been reported
      that several endotoxin and proinflammatory cytokines inhibit CCR2 expression in
      vitro in human monocytes. We report here that lipopolysaccharides (LPS) down
      regulated CCR2 expression both in vitro and in vivo. Injection of LPS into mice
      dramatically reduced the expression of CCR2 on the surface of peripheral blood
      cells and completely blocked macrophage infiltration into the peritoneal cavity
      in response to thioglycollate elicitation. In addition, treatment of mice with
      LPS reduced their efficiency to clear Listeria monocytogenes infection. These
      results suggest that down-regulation of CCR2 and blockage of monocyte
      infiltration may contribute to the inhibition of macrophage function in vivo by a
      low dose of LPS.

PMID- 10088611
TI  - Transfection of human macrophages by lipoplexes via the combined use of
      transferrin and pH-sensitive peptides.
AB  - The crucial function of macrophages in a variety of biological processes and
      pathologies render these cells important targets for gene therapeutic
      interventions. Commonly used synthetic gene delivery vectors have not been
      successful in transfecting these non-dividing cells. A combination strategy
      involving cationic liposomes to condense and carry DNA, transferrin to facilitate
      cellular uptake, and the pH-sensitive peptide GALA to promote endosome
      destabilization, resulted in significant expression of a luciferase gene.
      Transfection of macrophages was dependent on the degree of differentiation of the
      cells. The quaternary complexes of cationic liposomes, DNA, transferrin, and GALA
      exhibited a net negative charge, which may obviate a limitation of cationic
      synthetic vectors in vivo. The lack of cytotoxicity and the expected lack of
      immunogenicity of these complexes may render them useful for gene delivery to
      macrophages in vivo.

PMID- 10088612
TI  - Dietary fat, calories, and prostate cancer risk.

PMID- 10088613
TI  - Dietary fat, serum estrogen levels, and breast cancer risk: a multifaceted story.

PMID- 10088614
TI  - Measure once or twice -- does it really matter?

PMID- 10088615
TI  - Beans and bran -- fiber data come under fire.

PMID- 10088616
TI  - Esophageal cancers: changing character, increasing incidence.

PMID- 10088617
TI  - Cancer strikes the comic pages.

PMID- 10088618
TI  - New standard of care for cervical cancer sets stage for next questions.

PMID- 10088619
TI  - Safe cigarette alternatives? Industry critics say 'not yet'.

PMID- 10088620
TI  - Epidemiologic evidence and human papillomavirus infection as a necessary cause of
      cervical cancer.

PMID- 10088621
TI  - Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial
      growth factor expression.
AB  - BACKGROUND: A sedentary lifestyle coupled with excessive energy intake is
      speculated to be a factor associated with increased incidence of prostate cancer.
      We have investigated the effects of energy intake on prostate tumor growth in
      experimental animals. METHODS: Two transplantable prostate tumor models, i.e.,
      the androgen-dependent Dunning R3327-H adenocarcinoma in rats and the androgen
      sensitive LNCaP human carcinoma in severe combined immunodeficient mice, were
      studied. R3327-H tumor growth and relevant tumor biomarkers (proliferation index,
      apoptosis [programmed cell death], microvessel density, and vascular endothelial
      growth factor [VEGF] expression) were compared in ad libitum fed control rats, ad
      libitum fed castrated rats, and groups restricted in energy intake by 20% or 40%.
      A second set of experiments involving both tumor models examined tumor growth in
      ad libitum fed rats or in animals whose energy intake was restricted by 30% using
      three different methods, i.e., total diet restriction, carbohydrate restriction,
      or lipid restriction. All P values are two-sided. RESULTS: R3327-H tumors were
      smaller in energy-restricted or castrated rats than in control rats (P<.001).
      Tumors from energy-restricted rats exhibited changes in tumor architecture
      characterized by increased stroma and more homogeneous and smaller glands. In
      castrated rats, the tumor proliferation index was reduced (P<.0001), whereas
      apoptosis was increased in both energy-restricted (P<.001) and castrated (P<.001)
      rats. Tumor microvessel density and VEGF expression were reduced by energy
      restriction and castration (P<.003 versus control). Restriction of energy intake
      by reduction of carbohydrate intake, lipid intake, or total diet produced a
      similar inhibition of growth of R3327-H or LNCaP tumors. These effects were
      associated with reduced circulating insulin-like growth factor-I. CONCLUSIONS:
      Our observations are consistent with the hypothesis that energy restriction
      reduces prostate tumor growth by inhibiting tumor angiogenesis. Furthermore,
      dietary fat concentration does not influence prostate tumor growth when energy
      intake is reduced.

PMID- 10088622
TI  - Measuring response in solid tumors: unidimensional versus bidimensional
      measurement.
AB  - BACKGROUND: Tumor shrinkage is a common end point used in screening new cytotoxic
      agents. The standard World Health Organization criterion for partial response is
      a 50% or more decrease in the sum of the products of two measurements (the
      maximum diameter of a tumor and the largest diameter perpendicular to this
      maximum diameter) of individual tumors. However, theoretically, the simple sum of
      the maximum diameters of individual tumors is more linearly related to cell kill
      than is the sum of the bidimensional products. It has been hypothesized that the
      calculation of bidimensional products is unnecessary, and a 30% decrease in the
      sum of maximum diameters of individual tumors (assuming spherical shape and
      equivalence to a 50% reduction in the sum of the bidimensional products) was
      proposed as a new criterion. We have applied the standard response and the new
      response criteria to the same data to determine whether the same number of
      responses in the same patients would result. METHODS: Data from 569 patients
      included in eight studies of a variety of cancers were reanalyzed. The two
      response criteria were separately applied, and the results were compared using
      the kappa statistic. The importance of confirmatory measurements and the
      frequency of nonspherical tumors were also examined. In addition, for a subset of
      128 patients, a unidimensional criterion for disease progression (30% increase in
      the sum of maximum diameters) was applied and compared with the standard
      definition of a 25% increase in the sum of the bidimensional products. RESULTS:
      Agreement between the unidimensional and bidimensional criteria was generally
      found to be good. The kappa statistic for concordance for overall response was
      0.95. CONCLUSION: We conclude that one dimensional measurement of tumor maximum
      diameter may be sufficient to assess change in solid tumors.

PMID- 10088623
TI  - Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast
      cancer.
AB  - BACKGROUND: There is compelling evidence that estrogens influence breast cancer
      risk. Since the mid-1980s, dietary fat intervention studies have been conducted
      to investigate the effect of fat intake on endogenous estrogen levels. To further
      our understanding of the possible relationship between dietary fat and breast
      cancer, we conducted a meta-analysis of dietary fat intervention studies that
      investigated serum estradiol levels, and we reviewed the nature of the evidence
      provided by prospective analytic studies of fat consumption and breast cancer
      risk. METHODS: A computerized search of the English language literature on
      estrogen/estradiol and dietary fat intervention studies published from January
      1966 through June 1998 was conducted using the MEDLINE database. Pooled estimates
      were derived from the change in estradiol levels associated with fat reduction
      from 13 studies. Analyses were conducted separately for premenopausal and
      postmenopausal women and in both groups combined. RESULTS AND CONCLUSIONS:
      Statistically significant reductions in serum estradiol levels of -7.4% (95%
      confidence interval [CI] = -11.7% to -2.9%) among premenopausal women and -23.0%
      (95% CI = -27.7% to -18.1%) among postmenopausal women were observed, with an
      overall -13.4% (95% CI = -16.6% to -10.1%) reduction observed. The greatest
      reductions occurred in two studies in which dietary fat was reduced to 10%-12% of
      calories compared with 18%-25% of calories in the other studies. A statistically
      significant reduction in estradiol levels of -6.6% (95% CI = -10.3% to -2.7%)
      remained after exclusion of these two studies. Review of prospective analytic
      epidemiologic studies that allowed for dietary measurement error suggests that
      the possibility that reducing fat consumption below 20% of calories will reduce
      breast cancer risk cannot be excluded. IMPLICATIONS: Dietary fat reduction can
      result in a lowering of serum estradiol levels and such dietary modification may
      still offer an approach to breast cancer prevention.

PMID- 10088624
TI  - Pancreatic cancer risk and nutrition-related methyl-group availability indicators
      in male smokers.
AB  - BACKGROUND: Few risk factors for pancreatic cancer have been identified, with age
      and cigarette smoking being the most consistent. The protective effect associated
      with consumption of fruits and vegetables-the major dietary sources of folate-is
      suggestive of a role for factors influencing cellular methylation reactions;
      however, to our knowledge, no study has investigated this relationship. Whether
      biochemical indicators of methyl-group availability are associated with exocrine
      pancreatic cancer risk was the focus of this investigation. METHODS: We conducted
      a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer
      Prevention Study cohort of 29133 male Finnish smokers aged 50-69 years. One
      hundred twenty-six subjects with incident exocrine pancreatic cancer were matched
      by date of baseline blood draw (+/-30 days), study center, age (+/-5 years),
      trial intervention group, and completion of dietary history to 247 control
      subjects, who were alive and free from cancer at the time the case subjects were
      diagnosed. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined
      by use of conditional logistic regression. Reported P values are two-tailed.
      RESULTS: Serum folate and pyridoxal-5'-phosphate (PLP) concentrations showed
      statistically significant inverse dose-response relationships with pancreatic
      cancer risk, with the highest serum tertiles having approximately half the risk
      of the lowest (folate: OR = 0.45; 95% CI = 0.24-0.82; P for trend = .009, and
      PLP: OR = 0.48; 95% CI = 0.26-0.88; P for trend = .02). An increased pancreatic
      cancer risk was also observed with greater exposure to cigarettes (e.g., pack
      years [number of packs smoked per day x number of years of smoking], highest
      versus lowest quartile: OR = 2.13; 95% CI = 1.13-3.99; P for trend = .04).
      CONCLUSIONS: These results support the hypothesis that maintaining adequate
      folate and pyridoxine status may reduce the risk of pancreatic cancer and confirm
      the risk previously associated with cigarette smoking.

PMID- 10088625
TI  - Prospective study of adult onset diabetes mellitus (type 2) and risk of
      colorectal cancer in women.
AB  - BACKGROUND: The remarkable similarity of lifestyle and environmental risk factors
      for type 2 (non-insulin-dependent) diabetes mellitus and colon cancer has led to
      the hypothesis that diabetes may increase the risk of this cancer. We
      prospectively examined the relationship between diabetes and risk of colorectal
      cancer in a cohort of 118403 women aged 30 through 55 years who were without
      previously diagnosed cancer at baseline in 1976. METHODS: The women, who were
      enrolled in the Nurses' Health Study, were assessed for history of diabetes at
      baseline and during follow-up by use of biennial questionnaires. Self-reported
      diabetes was validated by information obtained from a supplemental questionnaire
      on symptoms and treatment and was confirmed by medical record review in a sample
      of the participants. Incident cases of colorectal cancer were ascertained through
      medical record review. All reported P values are two-sided. RESULTS: During 18
      years of follow-up (201061 person-years), we documented 892 new cases of
      colorectal cancer. After adjustment for age, body mass index (weight in kg/height
      in m2), physical activity, and other covariates, relative risks (RRs) were 1.43
      (95% confidence interval [CI] = 1.10-1.87; P = .009) for colorectal cancer, 1.49
      (95% CI = 1.09-2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56-2.21; P =
      .76) for rectal cancer, 1.56 (95% CI = 1.07-2.28; P = .02) for advanced
      colorectal cancer, and 2.39 (95% CI = 1.46-3.92; P = .0005) for fatal colorectal
      cancer. CONCLUSION: Our data provide support for the hypothesis that diabetes is
      associated with an increased risk of colorectal cancer in women.

PMID- 10088626
TI  - Dietary carotenoids and vitamins A, C, and E and risk of breast cancer.
AB  - BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are
      limited. Furthermore, studies of vitamins A, C, and E in relation to breast
      cancer risk are inconclusive. We have conducted a large, prospective study to
      evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We
      examined, by use of multivariate analysis, associations between intakes of
      specific carotenoids, vitamins A, C, and E , consumption of fruits and
      vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years
      in 1980) who were participating in the Nurses' Health Study. Through 1994, we
      identified 2697 incident cases of invasive breast cancer (784 premenopausal and
      1913 postmenopausal). RESULTS: Intakes of beta-carotene from food and
      supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely
      associated with breast cancer risk in premenopausal women. Strong inverse
      associations were found for increasing quintiles of alpha-carotene, beta
      carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A
      among premenopausal women with a positive family history of breast cancer. An
      inverse association was also found for increasing quintiles of beta-carotene
      among premenopausal women who consumed 15 g or more of alcohol per day.
      Premenopausal women who consumed five or more servings per day of fruits and
      vegetables had modestly lower risk of breast cancer than those who had less than
      two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] =
      0.58-1.02); this association was stronger among premenopausal women who had a
      positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those
      who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04).
      CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids
      and vitamins may reduce premenopausal breast cancer risk.

PMID- 10088627
TI  - p53 and genetic susceptibility to cervical cancer.

PMID- 10088628
TI  - Re: Multicenter case-control study of exposure to environmental tobacco smoke and
      lung cancer in Europe.

PMID- 10088629
TI  - Re: Autofluorescence bronchoscopy in the detection of squamous metaplasia and
      dysplasia in current and former smokers.

PMID- 10088630
TI  - Re: Autofluorescence bronchoscopy in the detection of squamous metaplasia and
      dysplasia in current and former smokers.

PMID- 10088631
TI  - Re: Cancer chemoprevention: progress and promise.

PMID- 10088632
TI  - Re: Nonmelanomatous skin cancer following cervical, vaginal, and vulvar
      neoplasms: etiologic association.

PMID- 10088633
TI  - Molecular insights into mechanisms of iron transport.
AB  - The past 3 years have witnessed extraordinary progress in our understanding of
      mammalian iron transport and homeostasis. The first transmembrane iron
      transporter has been found. Mutations in this protein, in two animal models with
      iron-transport defects, have helped to define the roles of this protein in vivo.
      The gene defective in patients with hereditary hemochromatosis has been
      identified, and much has been learned about the structure and function of its
      gene product. Finally, our ability to make a molecular diagnosis of hereditary
      hemochromatosis has called attention to new iron-loading disorders, including
      African iron overload and juvenile hemochromatosis.

PMID- 10088634
TI  - Iron deficiency in pregnancy: effects on the newborn.
AB  - Iron deficiency during pregnancy affects a significant portion of women in
      countries with low economic wealth and is not uncommon in pregnant women in
      industrialized countries. Inadequate intake of iron related to diets poor in
      bioavailable iron is often responsible for iron deficiency before pregnancy, and
      metabolic adjustments (such as mobilization of iron stores and increased
      absorption) are insufficient to meet increasing needs during pregnancy. The
      effects of iron deficiency on the fetus are still controversial. Numerous
      measures, including the evaluation of erythrocyte ferritin, favor the hypothesis
      that the level of iron stores in newborns is related to maternal iron status and
      that the materno-fetal unit is dependent on exogenous iron, which is necessary to
      prevent iron deficiency in both mothers and infants. In industrialized countries,
      iron supplements should be prescribed for pregnant women in the third trimester,
      when the need for iron is prominent. In developing countries, supplementation
      should be initiated as soon as possible after conception because of the high
      prevalence of iron deficiency at the onset of pregnancy. The results of studies
      comparing intermittent with daily supplementation remain controversial.

PMID- 10088635
TI  - Thrombosis in heritable hemolytic disorders.
AB  - Thromboses are a serious complication in patients with sickle cell disease,
      paroxysmal nocturnal hemoglobinuria, beta-thalassemia major, or thalassemia
      intermedia. Despite prophylaxis, thrombotic events can continue and can result in
      severe physical or mental debilitation or death of the patient. The fact that
      thrombosis does not occur in all patients with hemolytic anemias suggests that
      multiple factors interact to cause the coagulation crisis. Genetic modifiers,
      associated diseases, nutritional status, infections, environment, and treatment
      modalities are variables implicated in thrombophilia. The complexity confounds
      attempts to identify single causative agents in humans with hemolytic anemias. In
      the past year, mutations in putative genetic modifiers of the coagulation
      response have been examined as risk factors in patients with a history of
      thromboses; red cell binding sites on endothelial cells have been identified; and
      mouse models of thrombogenesis that permit experimental manipulation of single
      factors on a defined genetic background have been described.

PMID- 10088636
TI  - Role of red blood cells in thrombosis.
AB  - Most biomedical textbooks teach that coagulation and thrombosis are primarily a
      function of endothelial cells, platelets, and soluble coagulation factors. Red
      blood cells, in contrast, are generally regarded as innocent bystanders,
      passively entrapped in a developing thrombus as they flow through the
      vasculature. This review summarizes evidence that demonstrates an active role for
      red cells in normal and pathologic hemostasis. We then evaluate the possible
      molecular mechanisms whereby a usually inert erythrocyte can actively contribute
      to the processes of clot formation.

PMID- 10088637
TI  - The molecular and cellular biology of Fanconi anemia.
AB  - Fanconi anemia is a rare autosomal recessive disease characterized by multiple
      congenital abnormalities, bone marrow failure, and cancer susceptibility. The
      mean age of onset of anemia is 8 years, and the mean survival is 16 years. Death
      usually results from complications of bone marrow failure. Considerable progress
      in Fanconi anemia research has resulted from the recent identification and
      cloning of three Fanconi anemia genes. The current review describes the structure
      and function of the Fanconi anemia genes and describes the role of the encoded
      Fanconi anemia proteins in a cellular pathway controlling chromosome stability.

PMID- 10088638
TI  - Pathogenesis and pathophysiology of anemia in HIV infection.
AB  - Anemia is common in human immunodeficiency virus infection, particularly in
      patients with acquired immunodeficiency syndrome. Anemia is multifactorial. HIV
      infection itself causes anemia, probably as a consequence of HIV infection of
      stromal cells rather than HIV infection of hematopoietic stem cells. Other common
      causes of anemia in AIDS are anemia of chronic disease consequent on
      opportunistic infections, bone marrow suppression by antiretroviral therapy, and
      hemolytic anemia induced by oxidant drugs. Thrombotic microangiopathy is a
      significant complication of HIV infection and may respond to plasmapheresis.

PMID- 10088639
TI  - Apoptosis and polycythemia vera.
AB  - Polycythemia vera is an acquired clonal myeloproliferative disorder characterized
      by increased numbers of erythroid cells, often with a concomitant rise in
      neutrophils and/or megakaryocytes. Normally, erythropoietin is essential for the
      survival and proliferation of erythroid progenitors; however in polycythemia vera
      the erythroid progenitor cells can survive and develop in the absence of
      erythropoietin. Members of the Bcl-2 family of apoptosis regulators have been
      shown to mediate the erythropoietin-dependent survival of erythroid cells. In
      this article, recent advances in understanding the mechanisms used by erythroid
      progenitors from patients with polycythemia vera to control apoptosis, are
      discussed.

PMID- 10088640
TI  - Molecular basis for polycythemia.
AB  - This overview concentrates on familial and congenital polycythemias in the
      context of other polycythemic disorders, with emphasis on those with established
      molecular lesions. Recent advances in the regulation of erythropoiesis, as they
      may relate to polycythemic states, are discussed as a background for those well
      defined polycythemic states wherein the molecular defect has not yet been
      elucidated. Primary familial congenital polycythemias and congenital and familial
      secondary polycythemias, including hemoglobin mutants, methemoglobinemias and
      congenital 2,3-bisphosphoglycerate deficiency, are discussed. The most common
      primary polycythemia, polycythemia vera, as well as the only likely endemic
      congenital secondary polycythemia, known as Chuvash polycythemia, are discussed.

PMID- 10088641
TI  - Hereditary dehydrated and overhydrated stomatocytosis: recent advances.
AB  - The hereditary stomatocytoses and allied disorders are genetic defects of the
      erythrocyte membrane that result in abnormal permeability to the univalent
      cations Na+ and K+. Although rare, these conditions reflect abnormalities in
      physiologic mechanisms that are of paramount interest. All cases (as defined
      here) show increased plasma membrane permeability to Na+ and K+ and, to a greater
      or lesser degree, stomatocytic morphology. Dehydrated hereditary stomatocytosis,
      the most common form of hereditary stomatocytosis, is more heterogeneous than
      previously thought and includes kindreds showing pseudohyperkalemia or perinatal
      edema, or both. The gene responsible for both dehydrated hereditary
      stomatocytosis and familial pseudohyperkalemia, a nonhemolytic variant that
      presents with high plasma K+ levels, has been mapped to 16q23-qter. The cause of
      overhydrated hereditary stomatocytosis remains elusive despite the manifest lack
      of the enigmatic protein stomatin in the erythrocyte membrane. In all cases where
      splenectomy has been performed, this procedure has conferred a marked risk for
      thrombosis in adult life. This finding stresses the importance of diagnostic
      distinction between these conditions and hereditary spherocytosis.

PMID- 10088642
TI  - Long-term hydroxyurea treatment in young sickle cell patients.
AB  - Hydroxyurea is the first drug that, under well-organized, large-scale trials in
      adults, has shown a beneficial effect on the clinical course of sickle cell
      disease. Several small-scale trials have been conducted in children, but they
      used different therapeutic schedules, and only one was a single-blind crossover
      trial. Still, children are clearly good responders to the treatment because a
      rapid clinical improvement was observed, with decreased frequencies of vaso
      occlusive crises, acute chest syndromes, and transfusion requirements. Despite
      large interindividual variations, virtually all the children studied increased
      their fetal hemoglobin, mean corpuscular volume, and total hemoglobin. Follow-up
      varied from 6 months to 59 months. More than in adults, the fetal hemoglobin
      increase was sustained, and few side effects were observed. Large-scale, placebo
      controlled studies seem no longer needed. Guidelines concerning patient
      selection, dosing schedules, and monitoring protocols as well as exhaustive
      registries for the detection of long-term side effects are necessary.

PMID- 10088643
TI  - Bibliography. Current world literature. Erythrocytes and their disorders.

PMID- 10088644
TI  - Reconstructing the history of human limb development: lessons from birth defects.
AB  - A major goal of biology has been to understand the developmental mechanisms
      behind evolutionary trends. This has led to a growing interest in studying the
      molecular basis of the evolution of developmental programs such as those
      mediating the diversification of tetrapod limbs. Over the last 10 y, it has
      become clear that the genes and general developmental programs used to build a
      limb are strongly conserved among widely disparate species. This finding suggests
      that altered regulation of the timing and locations of developmental events may
      be responsible for the morphologic variation observed among some species.
      However, genetic analyses of the regulatory regions of genes controlling
      vertebrate developmental programs are very limited. Characterization of the
      genetic basis of human birth defects of the limb provides an opportunity to
      dissect the developmental programs used to modify the architecture of the
      hominoid limb. This may allow us to assess the relative contributions of altered
      gene regulation to morphologic variation among species and reconstruct the
      evolutionary history of the hominid limb. Such insight is also important because
      morphologic differences in the hominid upper limb have been correlated with the
      use of tools, and tool making is often regarded as the milestone that marked the
      emergence of the genus Homo.

PMID- 10088645
TI  - Induction of anaphylaxis in mouse intestine by orally administered antigen and
      its prevention with soluble high affinity receptor for IgE.
AB  - Early symptoms of food allergy, including diarrhea, are caused by IgE-mediated
      anaphylactic reactions. To clarify the mechanisms of IgE-mediated anaphylactic
      reactions in the intestine induced by orally administered antigen, a mouse model
      was established by s.c. implantation of a murine hybridoma capable of producing
      monoclonal anti-trinitrophenyl IgE antibody. Morphologic and immunologic changes
      in the intestine, as well as the effect of the soluble high affinity IgE receptor
      alpha chain, were investigated after oral challenge with antigen in this mouse
      model. Diarrhea, a decrease in s.c. blood flow, an increase in vascular
      permeability, a substantial increase in serum histamine levels, and noticeable
      infiltration of mast cells and IgE-bearing cells into the lamina propria were
      observed around 30 min after antigen challenge. However, these changes were
      efficiently prevented by pretreatment of the mice with the soluble high affinity
      IgE receptor alpha chain. These findings suggested that oral administration of
      antigen actually induced anaphylactic shock in our mouse model. This reaction was
      most likely to be mediated by mast cell activation, in response to the IgE
      antigen complex, and a soluble form of the high-affinity IgE receptor efficiently
      prevented this IgE-mediated anaphylactic reaction by trapping free IgE.

PMID- 10088646
TI  - Altered immune function in human newborns after prenatal administration of
      betamethasone: enhanced natural killer cell activity and decreased T cell
      proliferation in cord blood.
AB  - During the course of human pregnancy, glucocorticoid (GC) treatment is given when
      preterm delivery is expected. This treatment is successful in stimulating the
      development of the fetal lung. However, in animal studies, a number of side
      effects of perinatal GC treatment have been described. The aim of the present
      study was to evaluate in humans the effects of antenatal GC treatment on
      development of the immune system. In addition, we examined the development of
      immune reactivity in infants born preterm and at term who did not receive GC
      treatment antenatally. We tested mitogen-induced T cell proliferation, natural
      killer cell activity, and lipopolysaccharide-induced IL-6 production in cord
      blood samples. We found that there is a significant effect of gestational age on
      the capacity of T cells to proliferate and of natural killer cells to kill K562
      tumor cells. The capacity to produce IL-6 does not change between gestational age
      26 and 41 wk. Moreover, our results show that antenatal treatment with GC does
      have immunomodulatory effects: T cell proliferation is decreased in infants born
      very preterm (gestational age 26-31 wk) as well as in infants born between 32 and
      36 wk of gestation. In contrast, the activity of natural killer cells is only
      increased in GC-treated infants born between 26 and 31 wk. We did not observe a
      significant effect of antenatal GC treatment on the capacity to produce IL-6.

PMID- 10088647
TI  - Hyperoxia and glucocorticoid modify retinal vessel growth and interleukin-1
      receptor antagonist in newborn rabbits.
AB  - Retinopathy of prematurity (ROP) is characterized by inhibition of the growth of
      the retinal vessels and subsequent neovascularization. Pharmacologic doses of
      glucocorticoids are known to decrease growth and to suppress inflammation. The
      aim of the present study was to investigate whether hyperoxia and/or
      glucocorticoid affect the growth of the retinal vessels and the expression of the
      anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra). The following
      treatments were given to newborn rabbits during the rapid growth of retinal
      vessels: 1) placebo and room air (n = 14); 2) dexamethasone (Dx) at 1 mg/kg/d
      during d 3 to 8 and room air (n = 14); 3) placebo and 100% oxygen (d 3 to 7) (n =
      14); 4) Dx and O2 (n = 16). On d 12, the eyes were studied for retinal vessel
      length and vascular surface area from India ink-perfused vessels. When indicated,
      retinas were harvested on d 7 and studied for the expression of IL-1ra mRNA using
      Northern blot analysis. Hyperoxia decreased the length and area of the retinal
      vessel complexes (p < 0.01) and induced neovascularization in three of eight
      animals (38%). Dx decreased the length and area (p < 0.01) and tended to increase
      the tortuosity of the retinal vessels. Dx did not potentiate the hyperoxia
      induced suppression of retinal vessel growth and prevented the hyperoxia-induced
      neovascularization (p = 0.04). Hyperoxia inhibited the expression of IL-1ra mRNA,
      whereas Dx ameliorated the hyperoxia-induced suppression of IL-1ra. According to
      present results, glucocorticoid decreases the retinal vessel growth and may
      decrease the hyperoxia-induced neovascularization. We propose that immature and
      damaged retinal vessels are affected by pharmacologic dosage of glucocorticoid.

PMID- 10088648
TI  - Possible protective role of growth hormone in hypoxia-ischemia in neonatal rats.
AB  - Perinatal asphyxia still constitutes a clinical hazard associated with
      considerable neurologic morbidity. Several growth factors, including insulin-like
      growth factor-I (IGF-I), have been reported to have a neuroprotective effect in
      experimental models of hypoxic ischemia (HI). In the present study, we have
      applied solution hybridization for quantification of the time course for mRNA
      expression of IGF-I, IGF-I receptor, and growth hormone (GH) receptor after HI in
      7-d-old rats. There was a significant increase in IGF-I mRNA in the damaged
      hemisphere 72 h (1.19 +/- 0.28 vs 0.48 +/- 0.02 amol/microg DNA, p < 0.05) and 14
      d (0.61 +/- 0.18 vs 0.19 +/- 0.05 amol/microg DNA, p < 0.05) after HI. In the
      contralateral hemisphere, both IGF-I and GH receptor mRNA had increased by 14 d
      after the insult (0.36 +/- 0.042 vs 0.13 +/- 0.011, p < 0.05, and 0.31 +/- 0.013
      vs 0.11 +/- 0.004 amol/microg DNA, p < 0.001, respectively). There were no
      changes in IGF-I receptor mRNA throughout the study period. We have also
      evaluated the neuroprotective effect of GH after HI in neonatal rats. GH
      administered s.c. after HI in daily doses of 50 and 100 mg/kg provided a moderate
      neuroprotection of 20%. These results suggest a role for the GH/IGF-I axis in the
      neurochemical process leading to HI brain injury.

PMID- 10088649
TI  - Correlation of flow probe determinations of common carotid artery blood flow and
      internal carotid artery blood flow with microsphere determinations of cerebral
      blood flow in piglets.
AB  - We investigated whether blood flow determined by a flow probe situated on one
      common carotid artery provided an accurate estimation of unilateral cerebral
      blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated
      piglets, blood flow determined by an ultrasonic flow probe placed on the right
      common carotid artery was correlated with CBF determined by microspheres under
      two experimental conditions: 1) before ligation of the right external carotid
      artery with both the right external and internal carotid circulations intact
      [common carotid artery blood flow (CCABF) condition], and 2) after ligation of
      the right external carotid artery (ipsilateral to the flow probe) with all
      residual right-sided carotid artery blood flow directed through the right
      internal carotid artery [internal carotid artery blood flow (ICABF) condition].
      The left carotid artery was not manipulated in any way in either protocol.
      Independent correlations of unilateral CCABF and ICABF with microsphere
      determined unilateral CBF were highly significant over a 5-fold range of CBF
      induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p <
      0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF
      was 1.68 +/- 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The
      slope of the correlation of unilateral ICABF versus unilateral CBF did not differ
      significantly from unity (1.06 +/- 0.15), and the y intercept did not differ
      significantly from zero [-1.3 +/- 5.2 (SEM) mL]. Consequently, unilateral ICABF
      determined by flow probe accurately reflected unilateral CBF determined by
      microspheres under these conditions. Flow probe assessments of CCABF and ICABF in
      piglets may provide information about dynamic aspects of vascular control in the
      cerebral circulation that has heretofore been unavailable.

PMID- 10088650
TI  - Insulin-like growth factor-I (IGF-I) ameliorates and IGF binding protein-1 (IGFBP
      1) exacerbates the effects of undernutrition on brain growth during early
      postnatal life: studies in IGF-I and IGFBP-1 transgenic mice.
AB  - Insulin-like growth factor-I (IGF-I) plays an important role in the stimulation
      of postnatal brain growth. In transgenic (Tg) mice, IGF-I overexpression
      stimulates postnatal brain growth, whereas decreased IGF-I availability caused by
      ectopic brain expression of IGF binding protein-1 [(IGFBP-1), an inhibitor of IGF
      I action] retards postnatal brain growth. Because undernutrition during early
      postnatal development profoundly retards growth and maturation of the brain in
      rodents, we sought to determine the influence of IGF-I on undernutrition-induced
      brain growth retardation. Caloric restriction was imposed on IGF-I Tg mice, IGFBP
      1 Tg mice, and their non-Tg littermates by separating half of each litter from
      their dams during the suckling period, postnatal d 1 to 21. Undernutrition
      reduced the brain growth of each group of mice, but the growth of undernourished
      IGF-I Tg mice was comparable to that of well-fed control mice (increased 4.13-
      and 4.22-fold, respectively) and greater than that of undernourished control mice
      (increased 3.45-fold), whereas undernourished IGFBP-1 Tg mice exhibited less
      growth (increased 3.15-fold) than undernourished control mice. When the effects
      of undernutrition were examined in specific brain regions of each group, the same
      pattern was observed, and IGF-I was found to be more effective in preserving the
      growth of the regions with the highest transgene expression (cerebral cortex,
      hippocampus, and diencephalon). Despite undernutrition, IGF-I transgene
      expression stimulated overgrowth of these regions as well as that of the
      posterior medial barrel subfield, a somatosensory area of the cerebral cortex in
      which IGF-I may be especially important in development. These data indicate that
      IGF-I can ameliorate the brain growth retardation caused by undernutrition
      imposed during development, although it is unclear whether IGF-I directly opposes
      the impact of undernutrition or acts independently of nutritional status.
      Nonetheless, these findings raise the possibility that the relatively high IGF-I
      expression during early postnatal life may be responsible for sparing the brain
      from the full impact of undernutrition during this time in development.

PMID- 10088651
TI  - Glycine antagonist and NO synthase inhibitor protect the developing mouse brain
      against neonatal excitotoxic lesions.
AB  - The prevention of cerebral palsy and neuroprotection of the immature brain
      continue to be health care priorities. The pathophysiology of perinatal brain
      lesions associated with cerebral palsy seems to be multifactorial and includes
      pre- and perinatal factors such as preconceptional events, hormone and growth
      factors deficiencies, maternal infections with production of cytokines, and
      hypoxic/ischemic perfusion failures. Excitotoxic cascade could represent a common
      pathway that leads to neural cell death and subsequent brain damage. Brain
      injuries induced by ibotenate, a glutamatergic analog, which are essentially
      mediated through the N-methyl-D-aspartate receptor, mimic some aspects of the
      white matter cysts and transcortical necrosis observed in human perinatal brain
      damage. The purpose of the present study was to assess the protective role of
      several pharmacological agents, administered in conjunction with ibotenate,
      against induced excitotoxic lesions. We injected ibotenate in the developing
      mouse brain 5 d postnatally, after the full settlement of neuronal layers. Co
      treatment with kynurenic acid, an antagonist of the facilitating glycine site of
      the N-methyl-D-aspartate receptor, or with N(G)-nitro-L-arginine, an inhibitor of
      nitric oxide synthesis, induced a dose-dependent neuroprotective effect.
      Conversely, zinc gluconate, a blocking agent of the channel linked to the N
      methyl-D-aspartate receptor, and a free radical scavenger (U74389F), were unable
      to protect the developing brain against excitotoxic attack. These data help to
      clarify some molecular mechanisms involved in excitotoxic lesions of the
      developing mouse brain and permit us to envision new strategies in the prevention
      of cerebral palsy.

PMID- 10088652
TI  - Peripheral oxygenation in hypotensive preterm babies.
AB  - Monitoring oxygenation in peripheral tissues of preterm babies may be useful in
      understanding the redistribution of blood flow during hypotension. Hemoglobin
      flow and venous saturation were measured in the forearm using near infrared
      spectroscopy with venous occlusion and were used to calculate fractional oxygen
      extraction, oxygen delivery, and oxygen consumption. Thirty ventilated preterm
      babies (median birth weight 976 g) were studied; 15 were hypotensive and 15
      normotensive. Treatment for hypotension was dopamine alone (median dose 5
      microg/kg/min) in eight cases, 4.5% human albumin solution (20 mL/kg) with
      dopamine in five cases, and only a blood transfusion (20 mL packed cells/kg) in
      two cases. There was a weak correlation between hemoglobin flow and mean arterial
      blood pressure (r = 0.40, p = 0.03). In hypotensive compared with normotensive
      babies, there was a significantly lower median hemoglobin flow (10.2 versus 20.2
      micromol/100 mL/min, p = 0.0006), forearm oxygen delivery (37.8 versus 75.2
      micromol/100 mL/min, p = 0.0008), and oxygen consumption (11.0 versus 23.9
      micromol/100 mL/min, p = 0.006), but the fractional oxygen extraction (0.327
      versus 0.306, p = 0.48) and the blood lactate concentration (1.22 versus 1.20
      mmol/L, p = 0.44) were similar. Following treatment of hypotension, oxygen
      delivery (p = 0.02) and oxygen consumption (p = 0.04) increased to 64.2 and 21.7
      micromol/100 mL/min, respectively, but fractional oxygen extraction (p = 0.81)
      and blood lactate concentration (p = 0.94) after treatment were unchanged. VO2
      was variable in the forearm of human infants. It reduced when DO2 was low, and
      there was no evidence of tissue injury or switch to anaerobic metabolism.
      Measurements of peripheral tissue oxygenation seem to be of some value in
      understanding the pathophysiologic changes that occur with hypotension.

PMID- 10088653
TI  - Gasping and other cardiorespiratory patterns during sudden infant deaths.
AB  - To gain information on the cardiorespiratory changes occurring immediately before
      sudden infant death (SID), recordings of heart rate and chest wall impedance were
      analyzed in nine infants who had died at a median age of 4.8 mo (range 1-6 mo)
      while attached to a memory monitor. Postmortem diagnoses were sudden infant death
      syndrome in seven infants and mild bronchopulmonary dysplasia in two infants.
      Primary cause of the monitor alarm was bradycardia in all but two infants. Heart
      rate fell to < or = 15 bpm 7.5 min (range 1.4-25.2 min) after the first alarm;
      there was no indication of heart block or ventricular tachycardia. Apnea (> 20 s)
      began 0.3 to 13.7 min (median 2.7 min) after this alarm in five infants and 7 to
      20 s before it in three infants; in the remaining infant, stimulation occurred
      before any apnea. Gasping was already present at the time of the first monitor
      alarm in three infants and occurred within 2.7 min after it in a further four
      infants. One infant only began to gasp 13 min after the first monitor alarm. The
      duration of gasping ranged from 3 s to 11 min in those five infants in whom it
      was not interrupted by resuscitation. The latter was given to three infants 4,
      21, and 228 s after the monitor alarm but had no effect on the ongoing decrease
      in heart rate. Since gasping only occurs if PaO2 is < 5-15 mm Hg, it is most
      likely that the seven infants who gasped at or shortly after the first monitor
      alarm were already severely hypoxemic at that time. This hypoxemia developed in
      the absence of prolonged central apnea. The role of other mechanisms potentially
      resulting in severe hypoxemia, such as upper airway obstruction or rebreathing,
      remains to be determined.

PMID- 10088654
TI  - Antioxidant and cytotoxic effects of bilirubin on neonatal erythrocytes.
AB  - Bilirubin, the breakdown product of heme from erythrocytes, accumulates in the
      neonate in the first days of life. In recent years, the antioxidant properties of
      bilirubin have been demonstrated in vitro and in vivo, yet it is clear that
      bilirubin can be toxic to cells. To study the range in which bilirubin exerts its
      beneficial effect, we used erythrocytes derived from cord blood and incubated
      them with 0-60 mg/dL bilirubin combined with 3 g/dL BSA (bilirubin/BSA) to mimic
      physiologic and pathologic conditions. Oxidative stress was induced by incubating
      the erythrocytes with a solution of 0.6 mM H2O2 and 0.15 M CuSO4 to generate
      hydroxyl radical mediated injury. The loss of fluorescence of cis-parinaric acid
      and the degree of protein oxidation of erythrocyte membranes were assessed.
      Additionally, we determined erythrocyte membrane integrity, glucose-6 phosphate
      dehydrogenase activity, and adenosine triphosphatase activity before and after
      incubation with bilirubin/BSA. Incubation with bilirubin/BSA at concentrations up
      to 60 mg/dL and a bilirubin/BSA molar ratio of two was associated with dose
      dependent protection of erythrocytes against lipid peroxidation. However,
      concentrations of bilirubin equal to or exceeding 30 mg/dL and a bilirubin:BSA
      ratio of one were associated with increased protein oxidation, decreased
      erythrocyte glucose-6 phosphate dehydrogenase and adenosine triphosphatase
      activity, and altered cell membrane integrity. We conclude that bilirubin, at
      physiologic concentrations, protects neonatal red blood cells against oxidative
      stress in the presence of physiologic concentrations of BSA but that bilirubin
      concentrations of 30 mg/dL or higher and a bilirubin:BSA ratio of greater than
      one are associated with significant cytotoxicity.

PMID- 10088655
TI  - Bone turnover in preterm infants.
AB  - Total parenteral nutrition is associated with osteopenia in preterm infants.
      Insufficient calcium and phosphate are likely causes: aluminum contamination is
      another possible contributing factor as this adversely affects bone formation and
      mineralization. The study was designed to evaluate changes in biochemical markers
      of bone turnover in 22 preterm infants receiving total parenteral nutrition in
      comparison with 19 term infants. We collected urine and serum samples from 22
      preterm infants, mean gestational age 29 wk, within 48 h and again at 3 wk of
      life. We also collected urine samples from 19 term infants, mean gestational age
      39 wk, during the first day of life. Bone resorption was assessed by the
      measurement of urinary pyridinium cross-links by HPLC and ELISA and the N
      telopeptide of type I collagen by ELISA. Bone formation was assessed in premature
      infants by the measurement of serum osteocalcin. The N-telopeptide of type I
      collagen was higher in the preterm infants compared with term at baseline (p <
      0.01). There was no difference between the pyridinium cross-links in the preterm
      and term infants. All the biochemical markers of bone turnover increased
      significantly in the preterm infants during the first 3 wk of life, e.g. N
      telopeptide was a 153% change from baseline (p < 0.001). Aluminum in the total
      parenteral nutrition solutions did not cause a decrease in bone formation at the
      level administered (3-6 microg, 0.1-0.2 micromol x kg(-1) x d(-1)).

PMID- 10088656
TI  - Timing of peak serum cortisol values in preterm infants in low-dose and the
      standard ACTH tests.
AB  - The low-dose ACTH test seems to reveal mild cases of adrenal insufficiency and is
      beginning to be preferred over the standard ACTH test in the evaluation of
      adrenal suppression both in infants and in adults. The concentration-time profile
      of plasma cortisol in infants after a low ACTH dose is obscure. In this crossover
      study, we compared timing of the peak values in the low-dose and the standard
      ACTH stimulation tests in preterm and full-term infants. We performed the
      standard ACTH tests (250 microg/1.73 m2) and the low-dose ACTH tests (1
      microg/1.73 m2) on 10 infants (26-40 wk gestational age) and measured serum
      cortisol concentration at 0, 30, 40, 60, and 120 min by RIA. Nine of the infants
      had received postnatal glucocorticoid treatment, and most of them had also been
      treated with dexamethasone antenatally. In the low-dose test, the peak values
      occurred at 30 or 40 min in 9/10 patients. In the standard-dose test, the peak
      values occurred at 60 or 120 min in 8/10 patients. These results are comparable
      with those from adults. According to this study, blood samples for the low-dose
      ACTH test in infants should be taken before dosing and between 30 and 40 min
      after dosing.

PMID- 10088657
TI  - Effects of changes in ambient temperature on the Hering-Breuer reflex of the
      conscious newborn rat.
AB  - We questioned to what extent changes in temperature could affect the newborn's
      ventilatory inhibition provoked by lung inflation, or Hering-Breuer (HB)
      inflation reflex. Conscious newborn rats (3-4 d old) were studied in a double
      chamber airflow plethysmograph at ambient temperatures of 32 degrees C (slightly
      below their thermoneutrality), 24 degrees C (cold), and 36 degrees C (warm). At
      these ambient temperatures, the corresponding body temperatures averaged 35.4,
      31.0, and 37 degrees C. The HB reflex was triggered by negative body surface
      pressures of 5 or 10 cm H2O, and quantified as the duration of the expiratory
      time during the maintained inflation, either in absolute values or in relation to
      the control expiratory time. In cold the HB reflex decreased to 80%, and in warm
      it increased to 150%, of the values measured at 32 degrees C. Oxygen consumption,
      measured by an open flow system, averaged 59, 47, and 29 mL x kg(-1) x min(-1)
      at, respectively, 24, 32, and 36 degrees C. In cold, the ventilatory response to
      hypoxia (10% O2) was almost absent, that to hypercapnia (5% CO2) was greater, and
      that to hypoxia and hypercapnia combined was less than in warm. We conclude that
      in newborn rats the strength of the vagal inhibition on breathing, evaluated in
      the form of the HB reflex, is sensitive to temperature, becoming stronger as
      temperature increases. One contributing factor is the temperature-induced change
      in metabolic rate, whereas the role of temperature-induced changes in ventilatory
      chemosensitivity is variable. The strong temperature-dependency of the neonatal
      HB reflex implies that in newborns exposed to a warm environment breathing is
      more susceptible to inhibitory inputs.

PMID- 10088658
TI  - Monthly measurements of insulin-like growth factor I (IGF-I) and IGF-binding
      protein-3 in healthy prepubertal children: characterization and relationship with
      growth: the 1-year growth study.
AB  - The usefulness of measurements of IGF-I or IGF-binding protein-3 (IGFBP-3) in the
      clinical management of growth disorders is dependent on the extent of physiologic
      variation in their concentrations. Our purpose was therefore to investigate the
      longitudinal intraindividual variation in serum concentration of IGF-I and IGFBP
      3 in healthy prepubertal children. Monthly serum samples and auxologic
      measurements were taken over a period of 1 y from 65 prepubertal children (38
      boys, 27 girls; mean age 9.1 y, range 7.8-10.8). Concentrations of IGF-I and
      IGFBP-3 were measured by RIA. The mean (+/-SD) serum concentration of IGF-I in
      the children was 165 +/- 42.0 microg/L, with a mean coefficient of variation (CV)
      of 13.9% around the annual mean serum concentration for each child. The
      corresponding mean concentration of IGFBP-3 was 3273 +/- 604.5 microg/L, and the
      mean CV for each child was 9.7%. These monthly longitudinal variations in IGF-I
      and IGFBP-3 were parallel to changes in longitudinal growth. Short-term changes
      (1 mo) in IGF-I were positively correlated with changes in weight (r(s) = 0.42, p
      < 0.0005) and body mass index (r(s) = 0.45, p < 0.0005), and negatively
      correlated with minor intercurrent illnesses (-0.32; p < 0.05). Seasonal
      fluctuations also occurred, with short term changes in IGF-I (1 mo) and IGFBP-3
      (3 mo), increasing with increasing outdoor temperatures (r(s) = 0.30, p < 0.05
      and r(s) = 0.39, p < 0.005, respectively). We conclude, that there are
      significant changes in both IGF-I and IGFBP-3 that occur in association with
      growth, and that IGF-I is more sensitive than IGFBP-3 to short-term changes in
      weight, body mass index, and intercurrent illnesses. Physiologic short-term
      changes must therefore be taken into consideration when using serum levels of IGF
      I or IGFBP-3 in the evaluation of the short or slowly growing child.

PMID- 10088659
TI  - Decrease in the expression of the 3beta-hydroxysteroid dehydrogenase gene in
      human adrenal tissue during prepuberty and early puberty: implications for the
      mechanism of adrenarche.
AB  - Adrenarche is the increase of adrenal androgen secretion, mainly
      dehydroepiandrosterone and dehydroepiandrosterone sulfate, that occurs during
      prepuberty in higher primates. This event takes place at about 6-8 y of age in
      humans. It had been postulated that adrenarche might reflect an increase in the
      17,20 lyase:17OH-ase activity ratio of microsomal cytochrome P450c17. However,
      studies to demonstrate this mechanism have been unsuccessful. Because it has been
      described that virilizing adrenocortical carcinomas have high
      dehydroepiandrosterone sulfate secretion and low 3beta-hydroxysteroid
      dehydrogenase (3betaHSD) activity, in this study we evaluated the possible
      existence of maturative changes of the level of 3betaHSD type II mRNA in 11
      normal prepubertal and early pubertal human adrenals. Adrenal glands from
      subjects aged 0.1 to 13 y were obtained from organ donors, patients undergoing
      resection of the kidney for renal neoplasms or necropsies with less than 6 h of
      postmortem time. The expression of 3betaHSD type II gene was studied by dot blot
      in all samples and by relative reverse transcriptase (RT)-PCR in nine samples.
      The size of the transcripts was evaluated by Northern blot. Hybridization was
      performed using labeled human 3betaHSD cDNA probes. The uniformity of loading was
      tested using labeled human beta actine cDNA. The relative intensities of
      hybridization signals were quantified by scanning densitometry. The expected
      bands after relative RT-PCR were eluted, and radioactivity was measured in a
      scintillation counter. For the analysis of the results, subjects were divided
      into two groups as a function of age: group 1, less than 8 y (n = 6; range 0.1
      2.48 y) and group 2, equal or older than 8 y (n = 5; range 8-13 y). 3BetaHSD type
      II mRNA expression, analyzed by dot blot and relative RT-PCR, was significantly
      higher (p < 0.05) in group 1 (median and range 4.99, 0.50-8.00 and 16.3, 13.5
      40.0 arbitrary units, respectively) than in group 2 (0.15, 0.12-0.75 and 5.66,
      3.18-13.0, respectively). In conclusion, we have shown a decrease of the
      expression 3betaHSD type II gene as a function of age in prepubertal and early
      pubertal normal human adrenal tissue. This maturative change might be involved in
      the mechanism of human adrenarche.

PMID- 10088660
TI  - Ventilatory response and arterial blood gases during exercise in children.
AB  - To investigate the difference in ventilatory response to exercise between
      children and young adults, we administered a treadmill progressive exercise test
      to seven boys (aged 8 to 11 y [group A]) and six male young adults (aged 14 to 21
      y [group B]), who had a history of Kawasaki disease without significant coronary
      arterial lesions, and analyzed their arterial blood gases. There was no
      significant difference in arterial PO2 or the end-tidal to arterial oxygen
      tension difference during exercise between groups A and B. The arterial PCO2
      (PaCO2) at the ventilatory anaerobic threshold and at peak exercise was
      significantly lower in group A than in group B (p < 0.05). The arterial to end
      tidal carbon dioxide tension difference at peak exercise was significantly
      greater in group B than in group A (p < 0.05), whereas there was no significant
      difference at rest or at the ventilatory anaerobic threshold level. The arterial
      to end-tidal carbon dioxide tension difference at peak exercise was correlated
      with tidal volume (p < 0.01) and carbon dioxide production (p < 0.05) at peak
      exercise in all subjects. Although improvement in the physiologic dead
      space/tidal volume ratio during exercise was smaller in group A than in group B,
      there was no significant difference in total alveolar ventilation during
      exercise. However, the total carbon dioxide production during exercise was
      significantly smaller in group A than in group B. These data suggest that PaCO2
      during exercise is better estimated by end-tidal carbon dioxide tension in
      children than in young adults, that there is a significant difference in change
      of the PaCO2 during exercise between children and young adults, and that the
      decrease in PaCO2 in children is related to the mismatch between well-maintained
      alveolar ventilation and immature metabolic development in the working muscles
      during moderate-to-severe exercise.

PMID- 10088661
TI  - Modified starch enhances absorption and accelerates recovery in experimental
      diarrhea in rats.
AB  - Rice gruels have been used as home remedies to treat dehydration associated with
      diarrheal illness in developing countries. These preparations have produced
      conflicting results, most likely due to the heterogeneity of starch used. We
      investigated whether the modified tapioca starch, Textra (TX), at 5.0 or 10.0 g/L
      added to a 90 mmol/L Na+-111 mmol glucose oral rehydration solution (ORS)
      enhanced water and electrolyte absorption in two models of diarrhea. To induce a
      secretory state (model A), the jejunum of juvenile rats was perfused with 10
      mmol/L theophylline (THEO) under anesthesia and then perfused with the solutions
      indicated above. To produce chronic osmotic-secretory diarrhea (model B), rats
      had a magnesium citrate-phenolphthalein solution as the sole fluid source for 1
      wk, and then were perfused as the THEO-treated rats. Water, electrolyte, and
      glucose absorption were measured during both perfusions. As an extension of the
      perfusion studies, we compared how fast rats recovered from chronic osmotic
      diarrhea by offering them either water, ORS, or ORS containing 5.0 g/L TX along
      with solid food. Recovery rate markers were measured after 24 h and included
      weight gain, food and fluid intake, and stool output. In model A, addition of 5.0
      g/L TX to ORS reversed Na+ secretion and improved net water as well as K+ and
      glucose absorption, compared with THEO-treated rats perfused with ORS without TX.
      In model B, addition of TX to ORS increased water, Na+, K+, and glucose
      absorption, compared with rats perfused without TX. Increasing TX from 5.0 to
      10.0 g/L had no additional benefit. In recovery experiments, animals with free
      access to ORS with TX had significantly greater weight gain and decreased stool
      output compared with animals recovering with water or ORS without TX. Our
      experiments suggest that TX may be a useful additive to standard ORS to promote
      fluid and electrolyte absorption and may provide additional energy without
      increasing ORS osmotic load.

PMID- 10088662
TI  - Comparison of acetylation phenotype with genotype coding for N-acetyltransferase
      (NAT2) in children.
AB  - The present study focused on evaluation of the extent to which genotype coding
      for N-acetyltransferase agrees with acetylation phenotype in children at various
      ages. In 82 Caucasian children aged from 1 mo to 17 y (57 boys and 25 girls) and
      including 37 infants, the acetylation phenotype was evaluated from the urinary
      metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to 1
      methylxanthine (1X) after oral administration of caffeine. At the same time, by
      use of PCR and restriction analysis of amplified fragments of the N
      acetyltransferase gene, four nucleotide transitions were identified: 481C-->T
      (KpnI), 590 G-->A (TaqI), 803 A-->G (DdeI), and 857 G-->A (BamHI). The wild-type
      allele was detected in 27 (33%) children, and the slow acetylation genotype was
      found in 55 (67%) children. The results of the study show that the metabolic
      ratio AFMU/1X could be calculated only in 72 children, because in 10 (14%)
      infants <20 wk of age, AFMU was not detected. Determination of the relation
      between the acetylation phenotype and genotype revealed that 18 children (23%)
      containing at least one wild-type allele had AFMU/1X <0.4 (slow acetylation
      activity) and 7 (8%) of genotypically slow acetylators presented high metabolic
      ratio (high acetylation activity). We concluded that the disagreement between the
      acetylation phenotype and genotype is more often found in the group of children
      characterized by low AFMU/1X and that in small children only N-acetyltransferase
      genotype studies enable the detection of genetic acetylation defect.

PMID- 10088663
TI  - Defective IL2 gene expression in newborn is accompanied with impaired tyrosine
      phosphorylation in T cells.
AB  - Here we confirmed that IL2 mRNA expression in CD3-stimulated T cells is defective
      at birth. Because protein-tyrosine phosphorylation is an important part of
      signaling through CD3 and plays a key role in IL2 transcription, we further
      investigated whether impaired IL2 response to CD3 in newborns would be
      accompanied with an alteration of tyrosine phosphorylation. In this purpose, CD3
      induced tyrosine phosphorylation was evaluated comparatively in newborn and adult
      cells by immunoblotting of total cellular extract with an antiphosphotyrosine
      antibody. Results show that, in both peripheral lymphocytes or purified CD4 T
      cells from both cord and adult, CD3 stimulation could induce small even
      significant tyrosine-phosphorylation. Tyrosine phosphorylation occurs as soon as
      2' following CD3 ligation and was still evident up to 15-20'. Yet, by using a
      highly sensitive method to analyze CD3-induced accumulation of phosphorylated
      substrates, which consisted in adding pervanadate, an inhibitor of phosphatases,
      during the last 2 min of CD3 stimulation, we showed that the intensity of
      tyrosine phosphorylation was clearly decreased in cord cells. From these results,
      it is tempting to speculate that suboptimal capacities of cord T cells to up
      regulate tyrosine phosphorylation might contribute to defective IL2 production in
      neonates.

PMID- 10088664
TI  - Ontogeny of vascular angiotensin II receptor subtype expression in ovine
      development.
AB  - Angiotensin II (ANG II) increases arterial pressure in fetal sheep and may
      modulate cardiovascular adaptation before and after birth. The type 1 angiotensin
      II receptor (AT1R) predominates in adult vascular smooth muscle (VSM) and
      mediates vasoconstriction. In contrast, AT2R predominate in fetal tissues and are
      not known to mediate contraction. Although sheep are commonly used to study
      cardiovascular development, the ontogeny and distribution of VSM ATR subtypes is
      unknown. We examined ATR binding characteristics and subtype expression across
      the umbilicoplacental vasculature and in aorta, carotid, and mesenteric arteries
      from fetal (n = 44; 126-145 d gestation) and postnatal (n = 65; 1-120 d from
      birth) sheep using plasma membranes from tunica media and tissue autoradiography.
      Binding density (Bmax) was similar throughout the umbilicoplacental vasculature
      (p = 0.5), but only external umbilical arteries and veins and primary placental
      arteries expressed AT1R, whereas subsequent placental branches and fetal
      placentomes expressed only AT2R. Systemic VSM Bmax and binding affinity did not
      change significantly during development (p > 0.1). Fetal systemic VSM, however,
      expressed only AT2R, and binding was insensitive to GTPgammaS. Transition to AT1R
      in systemic VSM began 2 wk postnatal and was completed by 3 mo. Before birth,
      umbilical cord vessels are the primary site of AT1R expression in fetal sheep,
      and AT2R seem to predominate in systemic VSM until 2-4 wk postnatal.

PMID- 10088665
TI  - In vivo evidence for a myogenic response in the fetal pulmonary circulation.
AB  - In vitro studies have suggested that pulmonary arteries can exhibit a myogenic
      response and that this myogenic response may be potent during the perinatal
      period. However, whether a myogenic response can be demonstrated to exist in vivo
      and the potential role of the myogenic response on the regulation of pulmonary
      blood flow during fetal life is unknown. We hypothesized that an acute increase
      in pulmonary artery pressure resulting from partial compression of the ductus
      arteriosus (DA) in the fetus may simultaneously activate two opposing responses:
      1) blood flow-induced vasodilation (owing to shear stress); and 2) pressure
      induced vasoconstriction (owing to the myogenic response). To test this
      hypothesis, we studied the hemodynamic response to partial DA compression with
      and without inhibition of shear stress-induced vasodilation by nitric oxide
      synthase blockade in chronically prepared late-gestation fetal lambs. Without
      inhibition of nitric oxide synthase, pulmonary vascular resistance progressively
      decreased by 39 +/- 5% during the DA compression period (p < 0.05). In contrast,
      DA compression after nitric oxide synthase inhibition caused left pulmonary
      artery blood flow to initially increase and then steadily decrease toward a
      plateau value, and caused pulmonary vascular resistance to progressively increase
      by 28 +/- 4% above baseline (p < 0.05). The plateau value of pulmonary vascular
      resistance was reached in less than 5 min after the onset of DA compression. Left
      pulmonary artery blood flow after 10 min of partial DA compression did not change
      with the rise in pulmonary artery pressure; plateau values of pulmonary vascular
      resistance increased linearly with the increase in pulmonary artery pressure.
      These results support the hypothesis that the perinatal lung circulation has a
      potent myogenic response, and that this response may be masked in vivo under
      physiologic conditions by nitric oxide synthase activity. We speculate that the
      myogenic response may become a predominant regulatory mechanism of pulmonary
      vascular resistance when endothelium-dependent vasoreactivity is impaired, such
      as in persistent pulmonary hypertension of the newborn.

PMID- 10088666
TI  - Effect of beta-adrenergic stimulation on oxygen metabolism in the fetal lamb.
AB  - Catecholamines, which are released into the circulation during stress, increase
      fetal metabolism. This effect appears to be related to beta-adrenoreceptor
      stimulation. We examined the effect of isoproterenol infusion on umbilical blood
      flow, oxygen delivery and consumption, and glucose and lactate uptake in late
      gestation fetal lambs. Isoproterenol increased umbilical blood flow, but oxygen
      delivery to the fetus did not increase. Umbilical venous oxygen content fell
      linearly with the increase in umbilical blood flow. It is proposed that oxygen
      delivery to the sheep fetus is at or near a maximum and that oxygen delivery
      cannot be raised by increasing umbilical blood flow because oxygen diffusion at
      the placental site is limited. Fetal oxygen consumption increased initially but
      returned to control levels with an increase in infusion rate. Blood glucose
      concentration increased during isoproterenol infusion; this was due to release of
      glucose and not because of increased placental uptake. Fetal blood pH values fell
      in association with elevated lactate levels. It is proposed that elevated glucose
      concentrations resulted in increased metabolism of glucose, and because oxygen
      delivery could not be enhanced, increased anaerobic glycolysis caused lactate
      concentration to rise.

PMID- 10088667
TI  - Mature hippocampal astrocytes exhibit functional metabotropic and ionotropic
      glutamate receptors in situ.
AB  - Astrocytes closely contact neurons where they respond to neuronally released
      glutamate in immature brain slices. In previous studies, neither metabotropic nor
      ionotropic glutamate receptor-mediated responses were detected by imaging Ca2+ in
      astrocytes from mature (P21-P42) animals, suggesting astrocyte glutamate
      receptors only contribute to hippocampus physiology during development. In
      contrast to Ca2+ imaging, published electrophysiological experiments suggest P30
      P35 astrocytes have alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors. For this study, we imaged astrocytes in P31-P38 hippocampal slices to
      determine if metabotropic and ionotropic glutamate receptor activation elevates
      intracellular calcium in mature astrocytes. Drugs were perfused while [Ca2+]i was
      monitored (confocal imaging) in cells loaded with Calcium Green 1-AM. Imaged
      cells were subsequently identified as astrocytes by GFAP/S-100 immunostaining.
      Astrocytic Ca2+ increased after glutamate application in the presence of a
      glutamate uptake inhibitor. An agonist at group I/II metabotropic glutamate
      receptors, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD),
      elicited Ca2+ increases as did group I agonist 3,5-dihydroxyphenylglycine (DHPG),
      suggesting that mature astrocytes respond to glutamate via metabotropic glutamate
      receptors. AMPA also elicited Ca2+ elevations that were inhibited by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) and occurred after treatment with omega
      conotoxin MVIIC to block neurotransmitter release. These results demonstrate that
      astrocytes in mature hippocampus have functional ionotropic and metabotropic
      glutamate receptors that regulate astrocytic calcium levels. Glutamatergic
      regulation of astrocytic [Ca2+]i may be involved in synapse modeling, long-term
      potentiation, excitotoxicity and other events dependent on glutamatergic
      transmission in adult hippocampus.

PMID- 10088669
TI  - Intracellular signals and cytoskeletal elements involved in oligodendrocyte
      progenitor migration.
AB  - We have examined the potential roles of intracellular Ca2+ regulation and of
      multiple cytoskeletal elements in control of the directed migration of cultured
      oligodendrocyte progenitor cells (OPs). OPs were found to migrate in response to
      platelet-derived growth factor (PDGF) or to a lesser extent to basic fibroblast
      growth factor (FGF) in a non-additive manner. This response was inhibited by
      chelation of intracellular Ca2+ by using BAPTA-AM. OP migration was not evoked by
      the neurotransmitter agonists phenylephrine or methacholine, which elevate OP
      Ca2+ levels. Inhibition of the MAP kinase pathway with PD 098059 did not affect
      OP migration to PDGF. Within growth cone-like leading edges of migratory OP
      processes, monomeric and filamentous actin were found to be colocalized with
      myosin and filamentous actin was prominent in filopodia extending beyond the
      leading edge. Tubulin was distributed throughout OP processes and cell bodies.
      Inhibition of actin or tubulin polymerization, by using cytochalasin B or
      nocodazole, respectively, altered OP morphology and markedly impaired migration.
      Inhibition of the myosin ATPase by BDM, which prevents force-generating
      actin/myosin interactions, greatly inhibited the chemotaxic response at
      concentrations that did not disrupt cell morphology. These results indicate that
      growth factors stimulate OP migration by activating pathways which include
      intracellular Ca2+ regulation, and characterize the distribution of multiple
      cytoskeletal elements involved in the generation of directed OP movement.

PMID- 10088668
TI  - Interleukin-4 and interleukin-10 regulate IL1-beta induced mouse primary
      astrocyte activation: a comparative study.
AB  - The pro-inflammatory cytokine interleukin-1beta (IL-1beta) is strongly expressed
      during brain injury and is able to induce severe cellular brain damage via the
      production of soluble factors. Different processes regulate IL-1 biological
      activities, like the production of anti-inflammatory cytokines such as
      interleukin-4 (IL-4) and interleukin-10 (IL-10). In this report, we describe the
      sequential effects of IL-4 and IL-10 on the production of interleukin-6 (IL-6)
      induced by IL-1beta in mouse primary astrocytes and compare these effects to
      those of the synthetic glucocorticoid agonist, dexamethasone. IL-6 secretion and
      IL-6 mRNA expression were determined by ELISA assay and a comparative RT-PCR
      method, respectively. Incubation of mouse astrocytes in primary culture
      simultaneously with IL-1beta (10 ng/ml) + IL-10 (10 ng/ml) or IL-1beta +
      dexamethasone (10(-6) M) markedly reduced IL-1beta induced IL-6 secretion and IL
      6 mRNA expression, respectively, whereas simultaneous addition of IL-4 (10 ng/ml)
      did not alter the induction of IL-6 by IL-1beta. In contrast, after 24 h of IL
      1beta treatment, the level of IL-6 was decreased below constitutive levels, and
      this change was reversed by addition of IL-4. IL-6 production in IL-1beta
      pretreated cells was also increased by addition of IL-4, whereas IL-10 and
      dexamethasone had no effects. The delayed time dependent effect of IL-4 might be
      partially explained by the induction of IL-4 receptor alpha-chain mRNA expression
      by IL-1beta. Therefore, we conclude that IL-10 and dexamethasone have rapid
      immunosuppressive effects on the astrocyte response to IL-1beta stimulation,
      whereas IL-4, which has a delayed action, acts as an immune inducer.

PMID- 10088670
TI  - Immunocytochemical characterization of reactive optic nerve astrocytes and
      meningeal cells.
AB  - Regeneration in the adult central nervous system (CNS) is thought to be hampered
      by the lesion-induced activation of astrocytes and meningeal cells and the
      consecutive formation of a glial scar. The substrate properties of reactive
      astrocytes differ significantly from their neonatal counterparts, which promote
      axon growth, but in spite of intensive studies the underlying molecular changes
      are still not fully understood. We have used two cell culture systems to compare
      the expression of certain surface molecules on neonatal astrocytes, reactive
      astrocytes and meningeal cells in vitro. Both, neonatal and reactive adult
      astrocytes exhibited a very similar expression of growth promoting molecules
      (NCAM, L1, laminin, fibronectin, DSD-1 proteoglycan) and potential inhibitors
      (tenascinC, chondroitin sulfate, and NG2-proteoglycan), whereas we could not
      detect the inhibitory keratan sulfate on either astrocyte population. In
      contrast, meningeal cells expressed considerable levels of keratan sulfate, but
      only minimal amounts of NCAM. In addition, the much higher expression of
      extracellular fibronectin around meningeal cells implies an excess formation of
      extracellular matrix (ECM). In coculture experiments, embryonic retinal ganglion
      cell (RGC) axons clearly avoided meningeal cells and instead preferred even
      reactive adult astrocytes. Our results suggest that the expression of inhibitory
      keratan sulfate proteoglycans together with a lack of NCAM and an excess
      production of ECM may be responsible for the non-permissiveness of meningeal
      cells. Compared to reactive astrocytes, meningeal cells are even worse a
      substrate for growing axons. None of the molecules investigated, however, seems
      to account for the different substrate properties of neonatal and reactive adult
      astrocytes.

PMID- 10088671
TI  - Immunogold evidence suggests that coupling of K+ siphoning and water transport in
      rat retinal Muller cells is mediated by a coenrichment of Kir4.1 and AQP4 in
      specific membrane domains.
AB  - Postembedding immunogold labeling was used to examine the subcellular
      distribution of the inwardly rectifying K+ channel Kir4.1 in rat retinal Muller
      cells and to compare this with the distribution of the water channel aquaporin-4
      (AQP4). The quantitative analysis suggested that both molecules are enriched in
      those plasma membrane domains that face the vitreous body and blood vessels. In
      addition, Kir4. 1, but not AQP4, was concentrated in the basal approximately 300
      400 nm of the Muller cell microvilli. These data indicate that AQP4 may mediate
      the water flux known to be associated with K+ siphoning in the retina. By its
      highly differentiated distribution of AQP4, the Muller cell may be able to direct
      the water flux to select extracellular compartments while protecting others (the
      subretinal space) from inappropriate volume changes. The identification of
      specialized membrane domains with high Kir4.1 expression provides a morphological
      correlate for the heterogeneous K+ conductance along the Muller cell surface.

PMID- 10088672
TI  - Laminin receptor alpha6beta4 integrin is highly expressed in ENU-induced glioma
      in rat.
AB  - Laminins and their receptors influence neoplastic growth and invasiveness. We
      recently reported the abnormal expression of a laminin receptor, alpha6beta4
      integrin, in human astrocytomas. To further investigate the role of alpha6beta4
      in gliomas, we produced an experimental model of glioma in rat by transplacental
      ethylnitrosourea (ENU) administration. This animal model allowed us to study the
      timing of alpha6beta4 expression during tumor development and the topography of
      expression in the tumor and the surrounding tissue. Immunohistochemistry, in situ
      hybridization, and immunoprecipitation studies demonstrated that alpha6beta4
      heterodimer forms in experimental gliomas, and confirmed that alpha6beta4 is
      expressed diffusely in neoplastic cells and reactive astrocytes, but not in
      normal glia surrounding the tumors. Interestingly, alpha6beta4 was expressed from
      the early phases of tumor development, and more highly expressed by cells in the
      proliferative centers of the tumors. Both neoplastic cells and reactive
      astrocytes also expressed the glial growth factor (neuregulin) receptors, Erb-B2
      and Erb-B3. Finally, alpha6beta4 expression was reduced in a subset of tumor
      blood vessels. Thus, this study suggests a potential role for alpha6beta4 in the
      pathogenesis of gliomas. Furthermore, this is the first description of altered
      integrin expression in experimental gliomas; transplacental ENU-induced gliomas
      in rat will provide a useful model to study the role of altered adhesion in the
      pathogenesis of human gliomas.

PMID- 10088673
TI  - Evidence for extracellular calcium-sensing receptor mediated opening of an
      outward K+ channel in a human astrocytoma cell line (U87).
AB  - An extracellular calcium (Ca2+o)-sensing receptor (CaR) plays crucial roles in
      maintaining systemic calcium homeostasis. The CaR is also expressed in other
      cells uninvolved in systemic mineral ion homeostasis, including keratinocytes,
      fibroblasts, and neurons. In brain the CaR is widely distributed, being
      particularly abundant in neurons in subfornical organ, cingulate cortex,
      hippocampus, and cerebellum. It is also present in fiber tracts in rat brain,
      presumably in oligodendroglia and in cultured rat oligodendrocytes, suggesting
      that the CaR modulates the function of nonneuronal cells within brain. In this
      report, we show functional CaR expression in a human astrocytoma cell line (U87).
      Reverse transcription-polymerase chain reaction (RT-PCR) amplified a product from
      U87 cell RNA exhibiting >98% homology with the human CaR. Northern blot revealed
      a 5.5 kb transcript, similar to the principal transcript in human parathyroid,
      and a smaller 2.4 kb transcript. U87 cells expressed CaR protein as assessed by
      immunocytochemistry and Western blot using an affinity-purified, anti-CaR
      antiserum. Patch clamp analysis in the cell-attached mode revealed that raising
      Ca2+o from 0.75 to 1.75 or 2.75 mM produced approximately threefold increases in
      the open state probability (Po) of an outward K+ channel with a conductance of
      approximately 88 pS. A specific "calcimimetic" CaR activator, R-467 (0.5 microM),
      activated this K+ channel similarly, while its less active stereoisomer, S-467,
      did not. Thus U87 astrocytoma cells express both CaR mRNA and protein, and the
      receptor activates an outward K+ channel previously suggested to be involved in
      membrane polarization and cellular excitability.

PMID- 10088674
TI  - Dissection of astrocyte-mediated cues in neuronal guidance and process extension.
AB  - Neurites are believed to be guided by astrocyte boundaries during development. We
      have previously shown that in vitro astrocyte boundaries can be generated by
      combining two different astrocyte cell lines, one which is inhibitory to neurite
      outgrowth (Neu7) with one that is permissive (A7). The extracellular matrix
      molecules tenascin-C, chondroitin sulfate proteoglycans (CSPG) and keratan
      sulfate proteoglycans (KSPG) were implicated in boundary formation. We have now
      further addressed the roles of these molecules using additional astrocyte cell
      lines that differ in their potential to permit neurite extension and in their
      expression of extracellular matrix molecules. T34-2 and 27A1 cells are permissive
      to neurite extension. T34-2 cells express high amounts of tenascin-C, but very
      low levels of proteoglycans, while 27A1 cells express CSPG and KSPG, but very
      little tenascin-C. T34-2 cells formed boundaries to neurites, and these
      boundaries are greatly reduced in the presence of blocking antitenascin-C
      antiserum. The addition of the antiserum did not affect neurite extension. 27A1
      cells also formed boundaries without affecting neurite extension. Chondroitinase
      ABC, but not keratanase, treatment reduced the boundary, suggesting that CSPG is
      a major boundary component. These results demonstrate that astrocyte tenascin-C
      and proteoglycans are distinct components of astrocyte boundaries. More
      importantly, these results suggest that growing neurites can be directed to their
      targets by astrocyte-derived guidance molecules independent of effects on process
      extension.

PMID- 10088675
TI  - Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white
      matter.
AB  - The NG2 antibody, which recognises an integral membrane chondroitin sulphate,
      labels a significant population of cells in adult CNS white matter tracts of the
      rat optic nerve and anterior medullary velum (AMV). Adult NG2+ cells are highly
      complex with multiple branching processes and we show by EM immunocytochemistry
      that they extend perinodal processes, which contact nodes of Ranvier. NG2+ cells
      do not react to conventional immunohistochemical markers for adult glia and so we
      reservedly term them NG2P cells. In vitro, NG2 labels oligodendrocyte-type-2
      astrocyte (O-2A) progenitors that can give rise to oligodendrocytes or type-2
      astrocytes, depending on the culture medium. Thus, it is possible that NG2P cells
      may be derived from the same stem cells as oligodendrocytes. Interestingly, NG2+
      cells identified previously in adult CNS displayed phenotypic characteristics of
      O-2Aadult progenitors and it is possible that, like them, NG2P cells might retain
      the capacity of generating oligodendrocytes in the adult CNS. This may be an
      important role of NG2P cells in demyelinating diseases such as multiple
      sclerosis. It is significant therefore that the perinodal processes of NG2P cells
      contact the only sites of exposed axolemma in myelinated axons, so that NG2P
      cells are ideally situated to detect and respond to changes in axonal function
      during demyelination. A further implication of our finding is that NG2P cells may
      perform functions at nodes of Ranvier previously attributed to perinodal
      astrocytes, including the clustering and maintenance of sodium channels in the
      axon membrane at nodes, during development and following demyelination.

PMID- 10088676
TI  - Immunocytochemical localization of NaCh6 in cultured spinal cord astrocytes.
AB  - The expression of the alpha-subunit of voltage-gated sodium channel 6 (NaCh6) was
      examined in cultures of astrocytes from E18 rat spinal cord by using an antibody
      specific for NaCh6. Stellate cells with processes and flat, pancake-like
      astrocytes are the two morphological types predominantly present in these
      cultures. The antibody to NaCh6 labeled clusters at the cell body and along the
      length of the processes in stellate, process-bearing cells. Weak staining was
      observed in the flat, pancake-like astrocytes. Together with previous studies
      (Black et al., Mol Brain Res 23:235-245, 1994, Glia 14:133-144, 1995) that show
      that stellate cells express NaChs II and III (but not NaCh I) and flat cells
      express NaCh II, these results support the conclusions that there are different
      patterns of sodium channel expression between flat and stellate astrocytes and
      that multiple channel isoforms are expressed within the same cell. This study
      also suggests that NaCh6 may contribute to the electrical properties found in
      stellate astrocytes.

PMID- 10088677
TI  - Bugs, drugs, and bones: a pediatric infectious disease specialist reflects on
      management of musculoskeletal infections.

PMID- 10088678
TI  - Pyomyositis in children and adolescents: report of 12 cases and review of the
      literature.
AB  - Pyomyositis initially was observed more commonly in the developing world but now
      is reported with increasing frequency in the United States. The presentation is
      nonspecific and the differential diagnoses are many. We found the clinical
      history, laboratory findings, and response to treatment similar to those observed
      in different areas of the world. Magnetic resonance imaging (MRI) with gadolinium
      injection, in addition to helping to make the diagnosis, may help differentiate
      between early and late stages that help guide treatment. Coexisting bone changes
      (58%) may represent either the sensitivity of MRI to reactive inflammatory
      changes or the presence of a coexisting osteomyelitis. All patients responded to
      antibiotics and drainage if abscesses were present. Although the optimal duration
      of antibiotic therapy remains unclear, a shorter course should be considered in
      patients with a good clinical response, even when MRI shows nonspecific bony
      abnormalities. Percutaneous drainage was successful in five cases and may
      represent an alternative to the traditional surgical approach.

PMID- 10088679
TI  - Tuberculous osteomyelitis in young children.
AB  - Twenty-three cases of tuberculous osteomyelitis in children were reviewed. Age at
      diagnosis ranged from 10 months to 11 years; 17 patients were younger than 3
      years. At clinical presentation, patients were generally afebrile with local
      swelling and painful limb disability. Delay in diagnosis was common, with an
      average of 4.3 months. Laboratory data showed mild increase in white cell counts
      and erythrocyte sedimentation rates. However, C-reactive protein levels were all
      within normal limits except one. Roentgenograms demonstrated osteolytic lesions
      over metaphyseal areas with surrounding soft-tissue swelling. All patients had
      received BCG vaccinations at infancy. None of the patients had pulmonary
      tuberculosis. No familial or environmental history could be attributed to these
      victims, nor was any immunodeficient disease noted. Bacille Calmette-Guerin (BCG)
      vaccination was suspected to be the cause of tuberculosis in these young
      children. All patients received surgical debridement and oral antituberculosis
      chemotherapy for 1 year. After an average follow-up period of 71.4 months, all
      children had complete bony healing and excellent clinical results.

PMID- 10088680
TI  - Atrial and venous thrombosis secondary to septic arthritis of the sacroiliac
      joint in a child with hereditary protein C deficiency.
AB  - Septic arthritis and osteomyelitis in children is seldom accompanied by calf vein
      thrombosis and rarely by atrial thrombosis. We report the case of an 11-year, 5
      month-old boy with septic arthritis and osteomyelitis of the sacroiliac region
      who developed deep venous thrombosis, in addition to life-threatening right
      atrial thrombosis. After an intensive hematologic investigation, a hereditary
      protein C deficiency was revealed. The association of venous thrombosis with
      septic arthritis or osteomyelitis should raise the possibility of the presence of
      protein C deficiency.

PMID- 10088681
TI  - Peripelvic abscesses: a diagnostic dilemma.
AB  - Acute hematogenous peripelvic infections are common in tropical climates.
      However, in more temperate regions, this is a rare and often overlooked
      diagnosis. Because of the subtle and subacute nature of the symptoms, the
      diagnosis is often delayed. We report our experience with nine children treated
      for a hematogenous peripelvic infection. The hospital and clinic charts were
      reviewed of nine consecutive patients with the diagnosis of a peripelvic abscess.
      Patients ranged in age from 2 to 13 years. Symptoms were present from 5 to 20
      days. The most consistent symptom was a hip-flexion pseudocontracture (eight
      patients). The initial diagnosis was correct in only three patients. Computed
      tomography (CT) scan was diagnostic in all nine patients, providing diagnosis and
      localization. Seven of the nine patients underwent irrigation and debridement
      followed by a variable course of intravenous (i.v.) and oral antibiotics. All
      seven had rapid resolution of their symptoms. Two patients were treated with i.v.
      antibiotics alone, one of whom had a recurrence of symptoms. All nine patients
      had microbiologic confirmation of the infecting organisms [seven at surgery, one
      from blood cultures, one from sacroiliac (SI) joint aspiration]. Eight of the
      nine were infected by Staphylococcus aureus and one by group A Streptococcus. All
      had complete resolution of their symptoms at follow-up. Although acute
      retrofascial abscesses are rare in temperate climates, they should be considered
      in the differential diagnosis in the child with lower abdominal or hip pain. CT
      scan was the most helpful diagnostic test in these patients. Surgical drainage
      resulted in the most consistent results in this small series of patients.

PMID- 10088682
TI  - Pretreatment bone scan in SCFE: a predictor of ischemia and avascular necrosis.
AB  - Sixty-two consecutive patients with 73 slipped capital femoral epiphyses (SCFEs)
      underwent pretreatment planar technetium bone scan to identify the presence of
      ischemia of the femoral head. The relationship of pretreatment ischemia and the
      development of avascular necrosis (AVN) was evaluated after a minimum follow-up
      of 12 months. All patients were treated with spica casting or pinning across the
      physis. No forceful manipulation was performed. None of the 63 stable SCFEs
      demonstrated ischemia by bone scan, and none developed AVN. Of the 10 unstable
      SCFEs, six demonstrated ischemia by bone scan, and five of the six developed AVN.
      None of the four unstable SCFEs without ischemia on bone scan developed AVN.
      Pretreatment bone scan is a sensitive predictor for development of AVN in
      unstable SCFEs and may provide a method for evaluating interventional treatments
      for AVN associated with SCFE.

PMID- 10088683
TI  - Finding patients after 40 years: a very long term follow-up study of the Colonna
      arthroplasty.
AB  - Between 1952 and 1965, surgeons at the Los Angeles Shriners Hospital managed 23
      hips with the Colonna two-stage capsular arthroplasty, a procedure originally
      described in 1936 with very stringent indications for the treatment of childhood
      hip dysplasia. By using chart review, credit traces, telephone listings software,
      and the Internet, we found 17 (90%) of 19 patients known to be alive 40 years
      after surgery. Only four of 16 patients questioned have not undergone total hip
      arthroplasty, and these patients were no better candidates for the Colonna
      arthroplasty than were the 12 patients who have required hip-replacement surgery.
      We do not support revival of this now obscure procedure. However, we do attest
      that the average clinical investigator currently has access to tools that allow
      reliable location of patients for very long term follow-up. This technology will
      improve the accuracy and statistical power of outcomes research.

PMID- 10088684
TI  - Avascular necrosis after treatment of DDH: the protective influence of the
      ossific nucleus.
AB  - We retrospectively reviewed the results of open or closed reduction for
      developmental dysplasia of the hip (DDH) in 49 children younger than 12 months
      old, who had 57 hip dislocations. Group A (18 hips) developed partial or complete
      avascular necrosis (AVN), and group B (39 hips) did not develop AVN. Thirty-eight
      hips were treated by closed reduction, and 17 had open reduction. One patient
      with bilateral hip dislocation initially had closed reductions followed by
      bilateral open reduction 3 months later. With the numbers available for study,
      there was no significant difference in the occurrence of AVN with respect to
      variables such as preliminary traction, closed versus open reduction, Pavlik
      harness use, and age at the time of operative intervention. However, the presence
      of the ossific nucleus before reduction, detected either by radiographs (p <
      0.001) or ultrasonography (p = 0.033) was statistically significant in predicting
      AVN. Only one (4%) of 25 hips with an ossific nucleus developed AVN, whereas 17
      (53%) of 32 hips without an ossific nucleus before reduction developed AVN. Our
      results suggest that the presence of the ossific nucleus before closed or open
      reduction for DDH may decrease the risk of AVN.

PMID- 10088685
TI  - Transient synovitis: lack of serologic evidence for acute parvovirus B-19 or
      human herpesvirus-6 infection.
AB  - We evaluated children with transient synovitis for serologic evidence of
      infection with parvovirus B-19 (PVB-19) and human herpesvirus-6 (HHV-6) by using
      a prospective patient series in an urban children's hospital emergency department
      (ED). There were 20 children enrolled, aged 15 months to 6 years, diagnosed with
      transient synovitis. Clinical data were collected, and acute PVB-19 and HHV-6
      immunoglobulin G (IgG) and IgM serologic titers were measured on all patients.
      Ten patients returned in 4-6 weeks for convalescent titers. The mean age was 4.1
      years. Prodromal symptoms within a week of presentation were noted in 50% of
      patients, most commonly fever (25%) and upper respiratory infection (20%). Mean
      sedimentation rate was 11 mm/h (range, 2-22 mm/h), and mean peripheral white
      blood count was 11,000/microl (range, 6-21,000/ microl). No patient had increased
      acute or convalescent IgM titers for either PVB-19 or HHV-6, and no patient who
      returned for follow-up had an increase in serum IgG titers for either virus. A
      majority of patients (80%) had increased acute HHV-6 IgG titers, reflecting prior
      immunity to this virus. In conclusion, there is no evidence in this series that
      acute infection with PVB- 19 or HHV-6 causes or precedes transient synovitis.

PMID- 10088686
TI  - Complications of blade plate removal.
AB  - The AO fixed-angle blade plate is commonly used to obtain fixation in proximal
      femoral osteotomies. This device provides stable fixation and obviates the need
      for postoperative immobilization. There are no reports in the literature on the
      rate and types of complications associated with blade-plate removal. We report
      our rate and type of perioperative and early postoperative complications
      associated with removal of fixed-angle blade plates in a pediatric population.
      With an overall complication rate of 5.3% and a major complication rate of 2.0%,
      our study showed that removal of the blade plate was a relatively safe procedure
      in those patients troubled by prominent/painful hardware or skin breakdown.

PMID- 10088687
TI  - Transiliac exposure of the sacrum: a new surgical approach.
AB  - Biopsy or surgical approach of the midsacrum is difficult from the anterior,
      posterior, or superior approaches. I describe a lateral approach removing a piece
      of posterior ilium and entering the midsacrum through the sacroiliac joint. The
      approach was successfully used in an 8-year 7-month-old girl for the removal of
      an osteoid osteoma. The patient was monitored for 9 years 6 months until
      skeletally mature (age 18 years 1 month). This approach is applicable for biopsy
      or removal of benign tumors in the midsacrum in adults. Some developmental
      asymmetry of the pelvis may develop if it is used in children.

PMID- 10088688
TI  - Back pain during orthotic treatment of idiopathic scoliosis.
AB  - The incidence and etiology of back pain during orthotic management of idiopathic
      scoliosis was determined for 303 patients treated from 1980 through 1990 for a
      minimum of 1 year. All patients denied back pain before orthotic prescription.
      Thirty-four (11%) patients reported back pain after institution of brace
      treatment. A family history of scoliosis (p = 0.014) and vigorous sports
      activities (p < 0.001) were correlated with pain. Seventeen of 34 patients with
      pain showed >10 degrees of curve progression during bracing, whereas 67 of 269
      patients without pain progressed (p = 0.002). Four patients with pain and 11
      without were eventually found to have an underlying pathology
      (spondylolysis/listhesis). No other underlying pathologies were found. Night pain
      or a left thoracic curve pattern were not correlated with a serious underlying
      etiology. Back pain occurring after institution of brace treatment for idiopathic
      scoliosis is often associated with curve progression and is poorly correlated
      with a serious underlying pathology.

PMID- 10088689
TI  - Ambulation in patients with myelomeningocele: a 12-year follow-up.
AB  - Factors determining change in ambulatory status were studied over a 12-year
      observation time in 60 ambulating patients with myelomeningocele. There were 26
      female and 34 male subjects with a median age of 22 years (range, 12-54). We used
      the method of Lindseth to define the neurologic level of the lesion and
      classified walking ability according to the criteria of Hoffer. The prevalence of
      spasticity and spine and lower-limb deformities was assessed. Orthopedic and
      neurosurgical interventions and other medical events were registered, as well as
      occurrence of pressure sores, musculoskeletal pain, and use of orthoses. There
      were 19 patients with downward transitions in ambulatory level during the follow
      up time. Factors explaining deterioration in these 19 patients included
      deterioration of the neurologic level of lesion, spasticity, knee and hip flexion
      contractures, low-back pain, lack of motivation, as well as those of major
      medical events like stroke, recurrent septicemia, lower limb edema, and invasive
      surgical interventions.

PMID- 10088690
TI  - Complications of osteotomies in severe cerebral palsy.
AB  - Seventy-nine consecutive children with cerebral palsy who underwent osteotomies
      about the hip for subluxation or dislocation were studied retrospectively to
      determine risk factors that would correlate with postoperative complications of
      death, fracture, or decubitus ulcer. Except for the three patients who died, all
      of the children had > or = 1 year of follow-up. Twenty (25%) patients had at
      least one complication. Three children died; one at 1 week, one at 2 weeks, and
      one at 5 months after surgery. Sixteen patients sustained 25 fractures. All were
      managed with cast or splint immobilization in the clinic. Five patients developed
      decubitus ulcers requiring > or = 2 weeks of local care, but none required skin
      grafts or flaps. Complications occurred in 13 (68%) of 19 children with
      gastrostomies or tracheostomies but in only seven (12%) of the remaining 60
      children. Only one (8%) of 13 ambulatory patients had a complication compared
      with 19 (29%) of 66 nonambulatory patients. In conclusion, ambulatory function
      correlates well with the risk of complications after osteotomies. A nonambulatory
      patient with a gastrostomy or tracheostomy is at even greater risk. Fortunately
      the fractures and ulcers observed in this series healed uneventfully with no
      operative intervention.

PMID- 10088691
TI  - Objective assessment of dyskinesia in children with cerebral palsy.
AB  - The clinical classification of children with cerebral palsy is limited by
      multiple factors. Distinguishing between spasticity and dyskinesia is critical,
      because the outcome after standard orthopaedic and neurosurgical interventions is
      less predictable in children with cerebral palsy who have a significant
      dyskinetic component. This study applied computer-based analysis of gait to
      assess objectively the presence of significant dyskinesia in children with
      cerebral palsy. Three-dimensional gait analysis was performed on 18 normal
      children, 17 children with principally spastic cerebral palsy, and 23 children
      with significantly dyskinetic cerebral palsy. Children were assigned to the
      spastic or dyskinetic groups prospectively, based on clinical analysis by an
      experienced physician and physical therapist. The children with dyskinesia were
      found to have a significantly wider, and more variable normalized dynamic base of
      support, a smaller step profile (step length divided by step width), and a
      greater and more variable maximal lateral acceleration than the spastic and
      normal groups (mixed model analysis of variance, p = 0.0001). A predictive model
      of dyskinesia, (developed by logistic regression analysis), using these gait
      parameters, exhibited excellent sensitivity, correctly classifying 20 (87%) of 23
      children as dyskinetic. This study shows that children with dyskinetic cerebral
      palsy have distinct gait parameters and that objective assessment of dyskinesia
      in children with cerebral palsy is possible with computer-based analysis of gait.

PMID- 10088692
TI  - Circumferential periosteal sleeve resection: results in limb-length discrepancy
      secondary to poliomyelitis.
AB  - We report the results of circumferential periosteal sleeve resection of lower
      limb bones for mild degrees of limb-length discrepancy (mean, 3.5 cm) secondary
      to postpolio residual paralysis in 23 patients. Results were expressed by
      calculating percentage of length discrepancy of the operated-on limb with respect
      to the normal limb and gain in length in centimeters of the operated-on limb over
      the normal limb. All patients had a uniform trend of gain in length with response
      in the femur lasting for approximately 1 year, whereas that in the tibia
      persisted >2 years. Circumferential periosteal sleeve resection is a safe and
      reliable method of longitudinal bone-growth stimulation, providing consistent
      results, especially for mild to moderate discrepancies.

PMID- 10088693
TI  - Femoral shaft fracture treatment in patients age 6 to 16 years.
AB  - Traction followed by spica casting, the one method used to treat femoral shaft
      fractures in children that was used in the past, has given way to a multiplicity
      of methods today. To evaluate the morbidity and costs of these various methods,
      85 fractures in 81 patients age six to 16 years were evaluated. Early spica
      casting gave excellent results with low complications and low costs. All surgical
      treatments cost approximately the same: 3 times the cost of early spica casting
      and equivalent to traction followed by spica casting. Intramedullary flexible
      rods resulted in quicker healing and return to full weight bearing than did
      external fixation, which had the highest complication rate. One case of avascular
      necrosis in an 11-year-old girl treated with a reamed intramedullary rod suggests
      that this method is best reserved for children at or near skeletal maturity.

PMID- 10088694
TI  - The treatment of pediatric femur fractures with early 90-90 spica casting.
AB  - Twenty-three consecutive children younger than 6 years with a closed femoral
      shaft fracture stemming from low-energy trauma were treated with an early spica
      cast. With the patient under general anesthesia, a fiberglass cast was applied in
      sections. A short-leg cast was applied first, and then the patient was placed on
      the spica table. The hip and knee were flexed to 90 degrees, and traction was
      applied to the injured limb via the short-leg cast while the cast was completed.
      The popliteal fossa was well padded, and a valgus mold was placed at the fracture
      site. The average number of days in the spica cast was 42 (range, 18-57 days).
      Average shortening of the fracture at the time of cast removal was 1.0 cm (range,
      0.1-2.1 cm). Final patient examinations were performed 18-24 months after the
      fracture. Overgrowth averaged 1.1 cm in the femur (range, 0.5-1.9 cm) and 0.4 cm
      (0-0.7 cm) in the tibia. Limb lengths in each patient were within 1 cm of the
      contralateral limb when measured by scanogram and by blocks. The success of early
      spica cast treatment in this series can be attributed to strict patient selection
      and meticulous cast application.

PMID- 10088695
TI  - Salter-Harris type III and IV epiphyseal fractures in the hand treated with
      tension-band wiring.
AB  - We present tension-band wiring in the treatment of Salter-Harris types III and IV
      avulsion fractures in the hand. By placing a small-gauge wire through the
      insertion of the ligament into the fracture fragment, accurate reduction and
      stability, allowing early mobilization, are achieved, avoiding many of the
      pitfalls and complications of other methods of internal fixation. The technique
      is simple and adheres to important physiological and biomechanical principles.

PMID- 10088696
TI  - Surgical treatment of pediatric scaphoid fracture nonunions.
AB  - Scaphoid fractures in the pediatric population are uncommon but can usually be
      successfully managed with standard immobilization techniques. However, nonunions
      of pediatric scaphoid wrist fractures have been reported. We present the
      treatment and outcome of 13 pediatric scaphoid fracture nonunions in 12 children
      treated over an 18-year period. The average time elapsed between time of fracture
      and time of surgery was 16.7 months. Four of the nonunions were treated by using
      the Matti-Russe procedure, and nine were treated with Herbert screw fixation and
      iliac crest bone grafting. The average time of follow-up was 6.9 years (range, 2
      19 years). All cases went on to clinical and radiographic union. There was no
      statistically significant difference in range of motion or strength between the
      operative and nonoperative wrist. Eleven of 12 patients demonstrated an excellent
      rating based on the Mayo Modified Wrist score. The length of time for
      postoperative immobilization in the Herbert screw group was significantly less
      than that in the Matti-Russe group. Currently our standard approach to the
      treatment of scaphoid fracture nonunions in the skeletally immature patient is
      the use of the Herbert screw and iliac crest bone graft.

PMID- 10088697
TI  - An analysis of an air-ambulance program for children.
AB  - Air-ambulance services are extremely expensive to operate and maintain. The value
      of their existence has been questioned in this era of rationalization and
      downsizing. We examined the cost, safety, flight crew composition, types of
      trauma, and effectiveness of our air-ambulance program at the Children's Hospital
      of Eastern Ontario (CHEO) over a 3-year period, 1994-1997. During this time, 392
      children were aeroevacuated to CHEO, 113 surgical (29%), 136 medical (35%), and
      143 neonates (36%). Of the surgical cases, 43% were transferred for orthopaedic
      trauma, the commonest being fractured femur, 23% for general surgical cases, most
      common being thoracoabdominal trauma, and 22% for neurosurgical reasons, most
      commonly basilar skull fractures. The average response time (time from which the
      call was received to the time when the helicopter reached the patient site) for
      all of the cases was 46 min. The average travel time (time from departure of
      patient site to arrival at CHEO) for these same cases was 25.59 min. The air
      ambulance program for children in the Ottawa-Carleton Eastern Ontario areas, was
      found to be safe, effective, and allowed earlier specialized medical care to be
      provided.

PMID- 10088698
TI  - Clinical examination and investigation of the cruciate ligaments in children with
      fibular hemimelia.
AB  - In this retrospective study of abnormalities of the cruciate ligaments in
      children with fibular hemimelia, 69 knees were clinically examined, of which 20
      were further investigated by means of arthroscopy or nuclear magnetic resonance
      imaging (NMRI) for objective evidence of ligament lesions. The study allowed the
      type and incidence of cruciate ligament abnormalities found in this condition to
      be determined. The anterior cruciate ligament was affected (aplasia or
      hypoplasia) in 95% of cases and the posterior cruciate ligament in 60%. Although
      these lesions only rarely have functional consequences in such patients,
      pretreatment assessment should nevertheless include an active search for their
      presence to avoid subluxation of the knee during femoral lengthening, should this
      be the chosen approach.

PMID- 10088699
TI  - Congenital dislocation of the knee.
AB  - Between February 1988 and June 1995, 24 congenital dislocations of the knee
      joints (17 patients) were reduced with closed methods including immediate
      reduction, serial casting, or traction in patients from 10 min to 26 days old. At
      an average follow-up of 4 years and 10 months, an excellent or good result was
      achieved if there were no associated anomalies. Fair or poor results were the
      result of delayed treatment or associated musculoskeletal anomalies including
      arthrogryposis multiplex congenita or Larsen's syndrome. Routine check of the hip
      dislocation is suggested. Diagnosis with manual testing was difficult, and other
      methods such as radiography or sonography were suggested in combination to detect
      hip dysplasia. The dislocated knee should be reduced before treating the hip
      dislocation. Concomitant treatment of the congenital dislocation of the knee and
      the hip with Pavlik harness provided satisfactory results. When late,
      progressive, genu valgus deformity occurred because of global instability of the
      knee and asymmetric physeal growth, reconstruction of the medial structures of
      the knee and prolonged bracing provided good results.

PMID- 10088700
TI  - Surgical treatment of congenital dislocation of the patella.
AB  - Eleven patients with 17 involved knees were surgically treated for congenital
      dislocation of the patella between 1978 and 1993. Ten patients with 13 involved
      knees followed up for a minimum of 2 years postoperatively composed the study
      group. Six patients had both involved knees operatively treated. In four
      patients, congenital dislocation of the patella was associated with a
      recognizable syndrome. All patients had fixed, painful lateral dislocation of the
      patella that could not be reduced. The average age at presentation was 7 years
      and 9 months (range, 2 months to 15 years). All patients underwent an extensive
      procedure including lateral release and advancement of the vastus medialis
      obliquus. Skeletally immature children underwent medial transfer of the entire
      patellar tendon. Skeletally mature patients underwent medial transfer of the
      tibial tubercle. Ten patients with 13 involved knees were followed up for > or =
      2 years. Mean follow-up was 5.1 years (range, 1-17.5). At last follow-up, all
      patients reported a marked increase in activity tolerance and relief of pain.
      Average extension lag improved from 15 degrees before to 2 degrees after surgery.
      One superficial wound infection occurred; no patient developed a deep infection.
      One peroneal neurapraxia occurred but resolved with observation. Redislocation of
      the patella occurred in the immediate postoperative period in one patient.
      Operative treatment of congenital dislocation of the patella can predictably
      improve knee function when all aspects of the complex pathologic anatomy are
      addressed.

PMID- 10088701
TI  - Depression of the medial tibial plateau in early-onset Blount disease: myth or
      reality?
AB  - Patients with severe early-onset Blount disease (Langenskiold III or greater)
      often have the radiographic appearance of depression of the medial tibial plateau
      and delayed ossification of the epiphysis, adjacent physis, and metaphysis.
      Schoenecker and other authors recommended elevation of the medial plateau of the
      tibia for correction of this deformity. The purpose of this study was to assess
      the nature of the medial proximal tibia in these severe cases. Eight girls and
      two boys (17 tibiae) with severe early-onset Blount disease had standing
      radiographs and magnetic resonance imaging (MRI) evaluation. Average patient age
      was 5.8 years (range, 3-8 years). Eleven knees in eight patients underwent
      arthrography at the time of surgical correction of deformity. No tibia had MRI or
      arthrographic evidence of medial tibial joint "depression." The "empty"
      radiographic space was occupied by cartilage-density material. A smooth dye
      contour without pooling parallel to the femoral condyles was noted
      arthrographically in all instances. These findings do not support the concept of
      routine joint elevation in the correction of severe deformity associated with
      early-onset Blount disease.

PMID- 10088702
TI  - Genu valgum deformity in Hurler syndrome after hematopoietic stem cell
      transplantation: correction by surgical intervention.
AB  - Hematopoietic stem cell transplantation has increased the survival of patients
      with Hurler syndrome. Genu valgum occurs frequently in untransplanted patients
      and has been noted in 52% of our patients after stable engraftment. No
      deformities spontaneously corrected. We describe the orthopaedic management of
      genu valgum in Hurler syndrome. Medial epiphyseal stapling predictably affects
      angular deformity in these patients. Recurrence of deformities either after
      staple dislodgement or surgical removal can occur, and repeated stapling may be
      required. Surgical epiphyseal stapling has a role in the management of genu
      valgum in successfully engrafted Hurler patients. We discuss the relationship of
      this skeletal deformity to other skeletal deformities and alternative therapies
      for genu valgum.

PMID- 10088703
TI  - Valgus knee stress in lumbosacral myelomeningocele: a gait-analysis evaluation.

PMID- 10088704
TI  - Oxytocin modulates the pulsatile secretion of prostaglandin F2alpha in initiated
      luteolysis in cattle.
AB  - Subluteolytic doses of prostaglandin F2alpha analogue (oestrophan) given i.m. and
      oxytocin (OT) antagonist (CAP) and noradrenaline (NA) infused into the abdominal
      aorta were used to test the importance of luteal OT in pulsatile secretion of
      prostaglandin F2alpha (PGF) during luteolysis in heifers (n = 17). In experiment
      1, heifers were pre-infused for 30 minutes with saline on either day 17 of the
      oestrous cycle (group 1; n = 4) or on day 18 of the oestrous cycle (group 2; n =
      3), and with CAP (8 mg per animal) on day 17 of the oestrous cycle (group 3; n =
      4). Next, heifers were injected with oestrophan (30 microg per animal). Injection
      of oestrophan in Group 3 increased OT concentrations (P < 0.001) to values
      similar to those observed during spontaneous luteolysis (50 to 70 pg ml(-1)).
      PGFM concentrations in this group also increased (P < 0.001), but were lower (P <
      0.05) than the values in groups 1 and 2, CAP given prior to oestrophan decreased
      both PGFM elevation (P < 0.06) and its area under the curve (P < 0.01), compared
      to the saline pretreated heifers. In experiment 2 NA (4 mg) was infused twice for
      30 minutes at five hour intervals to release OT on day 17 of the oestrous cycle
      (n = 6). However, during hormone analysis it appeared that three of six heifers
      had elevated PGFM concentrations (group 1) and three others did not (group 2). NA
      caused the correlated increase of progesterone and OT secretion (r = 0.68; P <
      0.05) in both groups but it only influenced PGF secretion in group 1 only (P <
      0.05). We postulate that OT can amplify and modulate the course of induced
      luteolysis as a regulator of the amplitude of pulsatile PGF secretion. PGF
      analogue stimulates secretion of endogenous PGF from the uterus in cattle and
      this may be an important component of the luteolytic response to exogenous PGF.

PMID- 10088705
TI  - Diurnal fluctuations in rectal temperature of the Red Sokoto goat during the
      harmattan season.
AB  - Experiments were performed on 11 adult Red Sokoto goats (RSG) with the aim of
      determining their diurnal temperature fluctuations during the harmattan season.
      The rectal temperatures (RT) of goats were recorded with a standard clinical
      thermometer every hour from 06:00 to 19:00 hours. The RT of goats rose gradually
      from its minimum value of 38.3+/-0.1 degrees C at 06:00 hours and attained its
      peak value of 39.2+/-0.1 degrees C at 18:00 hours (P < 0.001). Thus, the RT
      values rose concurrently with increase in ambient temperature. The overall mean
      RT obtained was 38.7+/-0.1 degrees C. The diurnal fluctuation in the RT of the
      goats was 1.9+/-0.1 degrees C. There was a highly significant correlation between
      time of day and RT values (r = 0.947, P < 0.001). The results indicate a diurnal
      rhythm in the RT of the RSG, which agree with the established pattern of
      fluctuations in the RT of other breeds of goats. The high diurnal range of 1.9+/
      0.1 degrees C confirms that the harmattan season is thermally stressful to the
      RSG.

PMID- 10088706
TI  - Neuroendocrine changes in Dachshunds with mitral valve prolapse examined under
      different study conditions.
AB  - Neuroendocrine changes associated with canine mitral valve prolapse (MVP) were
      studied in 159 Dachshunds older than two years. In study 1, 102 dogs were sampled
      without controlling diet or fasting period. In good accordance with human
      findings, the MVP severity correlated positively with plasma renin activity and
      tended to correlate negatively with plasma aldosterone. These findings were not
      attributable to any coexistent mitral regurgitation (MR). In study 2, in which
      diet and fasting period were controlled, 57 Dachshunds younger than seven years
      were sampled twice through an i.v. cannula: once after approximately 15 minutes
      in lateral recumbency and again after 10 minutes of walking. In both study 2
      settings, neither MVP nor MR correlated significantly with plasma levels of
      renin, aldosterone, angiotensin-converting enzyme, norepinephrine, epinephrine,
      or cortisol. We conclude that the increased renin release found in early canine
      mitral disease is not reproducible under all study conditions, and that it
      correlates with the severity of MVP and not of MR.

PMID- 10088707
TI  - Comparative investigation on the effect of T-2 mycotoxin on lipid peroxidation
      and antioxidant status in different poultry species.
AB  - The effect of low dose T-2 toxin was investigated in chicken, duck and goose. The
      purpose of the present study was to investigate the effect of T-2 toxin on the
      lipid peroxidation and on the activity of glutathione redox system (amount of
      reduced and oxidised glutathione and the activity of glutathione peroxidase) in
      blood and liver. The treatment lasted days and two samples were taken, first at
      the time of lowest feed intake and second when the intake was the same as the
      control. It was found, that lipid per oxidation as detected by the amount of
      malondialdehyde increased in all of the species and tissues but the changes
      varied by species. The most sensitive species was goose followed by duck and
      chicken, and the most sensitive tissue was the liver followed by blood plasma and
      red blood cells.

PMID- 10088708
TI  - Locomotor, cardiocirculatory and metabolic adaptations to training in Andalusian
      and Anglo-Arabian horses.
AB  - The effects of two training programmes in 20 Andalusian and 12 Anglo-Arabian
      horses were evaluated by an increasing intensity work test at velocities of 4, 5,
      6, 7 and 8 m sec(-1). Heart rate was monitored and blood samples were drawn at
      rest and after each velocity to analyse packed cell volume, haemoglobin
      concentration, plasma lactate and potassium levels. Furthermore, the programmes
      were video-taped and stride length, duration and frequency, stance (restraint and
      propulsion), swing phase durations and stride vertical component were measured.
      The training protocol of the Andalusian horses produced significant decreases in
      the cardiovascular, haematological and metabolic responses to exercise.
      Locomotory training adaptation consisted of an increased stride frequency and a
      reduced stride length and vertical stride component. The last variable was the
      limiting factor of stride length both before and after training in the Andalusian
      horses. A different training protocol for show-jumping competition in Anglo
      Arabian horses failed to show significant differences in the studied parameters
      to the work test, although an increase in stride length at velocities of over 6 m
      sec(-1) was observed. Stride vertical component did not have an effect on the
      physiological response to exercise, either before or after training.

PMID- 10088709
TI  - Use of lipopolysaccharide (LPS) as a positive control for the evaluation of
      immunopotentiating drug candidates in experimental avian colibacillosis models.
AB  - The aetiologic agent of avian colibacillosis is Escherichia coli. Colibacillosis
      is a disease that causes mortality and production performance problems in
      chickens which results in economic losses for the poultry industry. It will be
      increasingly important for scientists to identify novel solutions that can be
      implemented which will provide poultry producers with a tool to manage this
      economically important disease. The purpose of this investigation was to
      determine whether lipopolysaccharide (LPS) could be used as a positive control to
      evaluate novel chemistries for immunopotentiator activity in battery or floor-pen
      avian colibacillosis models in chickens. In the battery study, subcutaneous
      administration of LPS to one-day-old broiler cockerels caused a significant
      reduction (P < 0.003) in all parameters of colibacillosis evaluated, i.e. mean
      air sac lesion scores, per cent air sac lesions, E. coli re-isolation and per
      cent mortality. However, in the floor-pen study, subcutaneous administration to
      one-day-old broiler chicks resulted in a numerical, but not statistically
      significant reduction (P < 0.1) in mortality associated with colibacillosis.
      These data indicate that LPS can be used as a positive control to evaluate the
      efficacy of immunopotentiator drug candidates in avian colibacillosis models.

PMID- 10088710
TI  - Effects of hypoxia on endocrine and metabolic responses to anaesthesia in ponies.
AB  - Some metabolic and endocrine effects of hypoxaemia were studied during halothane
      anaesthesia in six ponies. Each was anaesthetised twice; on one occasion a 20
      minute period of hypoxaemia (arterial oxygen tension between 4.4 and 5.8 [mean
      5.3] kPa) was imposed during 120 minutes of anaesthesia. On the second occasion
      arterial oxygen tension was maintained above 17 kPa throughout. Routine
      cardiovascular monitoring was performed and blood samples were taken to measure
      haematocrit, cortisol, insulin, glucose and lactate. Anaesthesia was associated
      with hypotension in both groups (mean ABP < 70 mmHg) but pulse rate changed
      little from control. Hypercapnia (PaCO2 > 7.0 kPa) developed in the normoxic
      group and acidosis was more severe than in the hypoxic group. Haematocrit changed
      little but was higher in the hypoxic group after the hypoxic period (0.39[0.06]
      vs 0.32[0.06] litre litre(-1)). Plasma cortisol increased significantly during
      anaesthesia in both groups (maximum values: hypoxic group 418[96], normoxic group
      492[102] nmol litre(-1)) and there was no significant difference between them.
      Glucose concentration increased in the hypoxic group and was significantly higher
      than in the normoxic group during the hypoxic period (8.8[1.5] vs 6.4[1.5] mmol
      litre(-1)). Insulin decreased in both groups but this was significant only in the
      normoxic group (from 34[19] to a nadir of 12[9] iu ml(-1)) and the groups were
      not significantly different. Lacticacidaemia developed in both groups but was
      more severe in the hypoxic group (maximum values 2.3[0.6] and 1.3[0.5] mmol
      litre(-1)). It was concluded that 20 minutes of hypoxia during halothane
      anaesthesia in ponies did not markedly alter the stress response already induced
      by anaesthesia.

PMID- 10088711
TI  - Effects of acute asphyxia at birth on subsequent heat production capacity in
      newborn pigs.
AB  - The effect of acute asphyxia at birth on subsequent ability to produce heat was
      investigated in 30 newborn pigs. A model of experimentally induced asphyxia
      consisting of the prevention of breathing within the first four minutes of life
      was used. Blood was sampled from an umbilical artery catheter within the first 75
      minutes of life for blood gas, pH, glucose, lactate and catecholamine analysis.
      After the treatment and 24 hours later, heat production capacity, shivering
      intensity and rectal temperature were measured 10 degrees C below
      thermoneutrality. Effects on blood gas parameters were severe but transient
      whereas alterations in carbohydrate metabolism were maintained during the first
      75 minutes (P < 0.05). Acute asphyxia at birth induced only minor alterations of
      thermoregulatory abilities during the first day of life: rectal temperature was
      lower one hour after birth (P < 0.05) and the postnatal increase in heat
      production capacity was less pronounced than in controls. It is suggested that
      the lower viability usually reported for piglets suffering from asphyxia during
      delivery is most likely to result from reduced vigour and colostrum intake, as
      well as altered carbohydrate metabolism early after birth.

PMID- 10088712
TI  - In vitro complex formation and inhibition of hepatic cytochrome P450 activity by
      different macrolides and tiamulin in goats and cattle.
AB  - In humans, clinically relevant drug-drug interactions occur with some macrolide
      antibiotics via the formation of stable metabolic intermediate (MI) complexes
      with enzymes of the cytochrome P4503A (CYP3A) subfamily. The formation of such
      complexes can result in a decreased biotransformation rate of simultaneously
      administered drugs. In previous studies it was shown that the veterinary
      antibiotic tiamulin was also able to form a stable MI complex in pigs and rats.
      In the present study the relative CYP3A inhibiting potency and MI complex
      formation of a series of macrolide antibiotics and tiamulin were studied in
      microsomal fractions of goat and cattle and in a cell-line expressing bovine
      CYP3A. Tiamulin and triacetyloleandomycin (TAO) were found to be effective
      inhibitors of CYP450 activity in all systems tested. Erythromycin and tilmicosin
      were found to be relatively less effective inhibitors of CYP450 activity in
      microsomes, and their activity in the bovine CYP3A4 expressing cell line was
      relatively weak. Tylosin was shown to be a weak inhibitor in microsomes and not
      in the cell line, whereas spiramycin had no effect at all. MI-complex formation
      measured by spectral analysis was seen with TAO, tiamulin, erythromycin and
      tylosin, but not with tilmicosin and spiramycin. Although additional factors play
      a role in vivo, these results may explain potential drug-drug interactions and
      differences between related compounds in this respect.

PMID- 10088713
TI  - Persistence of ivermectin in plasma and faeces following administration of a
      sustained-release bolus to cattle.
AB  - Six calves (weight 210 to 230 kg) were dosed with an intra-ruminal slow-release
      bolus prepared to deliver ivermectin at a low daily dosage for 135 days.
      Ivermectin concentrations in jugular blood 160 days post-treatment were
      determined by high performance liquid chromatography (HPLC) using fluorescence
      detection. Ivermectin plasma concentrations increased gradually to achieve the
      steady-state concentration (20 ng ml(-1)) at approximately four days post
      treatment, which was maintained for 120 days. The ivermectin peak plasma
      concentration (28.5 ng ml(-1)) was attained at 15 days post-administration of the
      bolus. The faecal ivermectin concentration rose to a maximal concentration of 4.1
      microg g(-1) at four days post-treatment, dropping to a steady-state
      concentration of around 1.18 microg g(-1) which was maintained up to 120 days
      post-treatment. Ivermectin was detected in both plasma (0.05 ng ml(-1)) and
      faeces (2.67 ng g(-1)) up to 160 days. The high levels of ivermectin recovered in
      faeces indicate that a large proportion of the dose released by the bolus (80 to
      90 per cent) is excreted in faeces.

PMID- 10088714
TI  - Fast resolution of hypercortisolism in dogs with portosystemic encephalopathy
      after surgical shunt closure.
AB  - The aim of this study was to investigate whether hypercortisolism in dogs with
      congenital portosystemic shunts disappeared after surgical closure of the shunts
      concomitantly with recovery from hepatic encephalopathy. We examined 22 dogs
      before and four weeks after partial surgical closure of a single, large
      congenital portosystemic shunt (PSS). Parameters measured to characterise the
      basal activity of the pituitary-adrenal axis were the cortisol:creatinine (c/c)
      ratio in home-sampled urine and total and free cortisol in plasma. The binding
      characteristics of cortisol binding globulin (CBG) in pooled pre- and
      postoperative plasma were also determined. Ammonia and bile acid concentrations
      were measured in plasma to characterise the liver perfusion and function.
      Clinical symptoms relevant to liver function, cortisol excess, and hepatic
      encephalopathy were recorded semiquantitatively using a standardized
      questionnaire. The dogs had hypercortisolism before surgery, which had normalized
      four weeks later. The pre- and postoperative concentrations (means +/- SEM) were,
      respectively, 238+/-45 nM and 126+/-19 nM for total cortisol, 15.5+/-2.6 nM and
      8.4+/-1.3 nM for free cortisol in plasma, 13.4+/-4.3 x 10(-6) and 3.9+/-0.4 x 10(
      6) for c/c in urine. The pre- and postoperative Bmax values of CBG were 41 and
      79, and Kd values were 3.8 and 5.5. The concentrations of ammonia were 217+/-23
      microM and 32+/-3.1 microM, and of bile acids 1 10+/-33 and 11.1+/-2.0 microM,
      respectively. We conclude that there is a close relation between portosystemic
      encephalopathy and hypercortisolism in dogs with PSS and that both deviations
      resolve completely within four weeks of closure of the shunt.

PMID- 10088715
TI  - The presence of muramidase released protein and extracellular factor protein in
      various serotypes of Streptococcus suis isolated from diseased and healthy pigs
      in Spain.
AB  - A total of 142 strains from different serotypes of Streptococcus suis isolated in
      Spain from diseased pigs (88 strains) and healthy carrier pigs (54 strains) were
      studied for the presence of a muramidase released protein (MRP) and an
      extracellular factor (EF). The following five phenotypes: MRP+EF+, MRP+EF-, MRP
      EF+, MRP+EF* and MRP*EF- were detected. A high percentage of S. suis serotype 2
      strains isolated from diseased pigs (84 per cent) belonged to phenotype MRP+EF+,
      but this phenotype has also been noticed in other serotypes (serotypes 1, 1/2 and
      14). Both proteins were detected in S. suis serotype 2 strains (26%) isolated
      from healthy carrier pigs and one of both proteins in serotypes 1 and 14
      (phenotype MRP+EF*). The isolation of S. suis strains from healthy pigs which
      have shown both proteins may support the epidemiological significance of these
      carriers in the maintenance, transmission and distribution of virulent strains
      within and between swine farms.

PMID- 10088716
TI  - Determination of behavioural traits of pure-bred dogs using factor analysis and
      cluster analysis; a comparison of studies in the USA and UK.
AB  - The questionnaire survey of Hart and Hart (1985, Journal of the American
      Veterinary Medical Association 186, 1811-1815) ranked the 56 most popular breeds
      of dog in the USA on 13 behavioural traits and is compared here with results of a
      similar survey conducted on the 49 most popular breeds in the UK. Of the 36
      breeds in common between the studies, 24 were similar for the traits
      aggressivity, reactivity and ease of housetraining between the two countries.
      However, the characteristics of nine breeds (Airedale Terrier, Old English
      Sheepdog, Welsh Corgi, Irish Setter, Standard Poodle, Beagle, Samoyed, Boxer,
      Dalmatian) differed markedly between the two countries, and a further three
      (Chihuahua, Scottish Terrier, Standard Dachshund) showed smaller, but probably
      meaningful, shifts. These differences should be recognised when giving advice to
      prospective owners, and when treating unwanted behaviour in these breeds.

PMID- 10088717
TI  - Increased interleukin-6 activity in the serum of ponies acutely infected with
      equine infectious anaemia virus.
AB  - Seven ponies were infected with the virulent wild-type Wyoming strain of equine
      infectious anaemia virus (EIAV). Infection status was monitored by serum reverse
      transcriptase activity, rectal temperature, and complete blood count.
      Preinfection serum and serum obtained during the initial febrile episode
      following infection were assayed for interleukin 6 (IL-6) activity. Postinfection
      IL-6 activity was significantly increased as compared to preinfection values. The
      magnitude of increase in IL-6 was positively correlated with reverse
      transcriptase activity (an indirect measure of viraemia) but was not correlated
      with rectal temperature. IL-6 production in response to EIAV infection may play a
      role in pathogenesis of disease, especially the hyperglobulinaemia and apparent
      polyclonal B cell activation in these horses.

PMID- 10088718
TI  - New insights into the mechanisms of nuclear segmentation in human neutrophils.
AB  - During human neutrophil differentiation, large portions of the genome condense
      and associate with the nuclear envelope to form filament-like structures. As a
      result, the nucleus of the mature neutrophil typically consists of a linear array
      of three or four lobes joined by thin, DNA-containing filaments. Despite the
      medical significance of neutrophil nuclear morphology, little is known about the
      events regulating neutrophil nuclear differentiation and its pathological states.
      This work presents a new model of the mechanisms governing nuclear filament
      formation in human neutrophils. This model is based on recent chromosome mapping
      studies in human neutrophils and on studies of genetic and pathological
      conditions affecting neutrophil nuclear shape. According to this model, filament
      assembly is initiated by factors that interact with specific regions of the
      genome in a hierarchical and dose-dependent manner. In this regard, the
      strategies governing the molecular interactions responsible for filament
      formation appear to resemble those involved in transcriptional silencing, a
      phenomenon that also affects the properties of extended chromosomal regions.
      According to the silencing paradigm, bound filament control Factors must recruit
      additional Filament Foehn factors which spread along adjacent DNA to mediate
      filament formation. A better understanding of the factors that shape the
      neutrophil nucleus may lead to new clinical tools for the diagnosis and
      manipulation of abnormal neutrophil differentiation.

PMID- 10088719
TI  - Effect of 1,25(OH)2D3 on bone morphogenetic protein-3 mRNA expression.
AB  - Bone morphogenetic proteins (BMPs) are members to the transforming growth factor
      beta superfamily. They induce ectopic bone formation in rat and are pleiotropic
      initiators of inducible osteogenic precursor cells. A lot of reports have studied
      the presence of BMPs and their effects on bone marker expression in many
      different cell lines, however none describe the regulation of BMP3 by different
      factors and expression conditions. When a human bone marrow stromal cell (HBMSC)
      culture was treated simultaneously with 1,25(OH)2D3 (10(-8) M) and BMP3 (2.5
      ng/ml), the total osteocalcin content in the cell layer and in the culture medium
      was higher than when the culture was treated with either factor alone (162%). To
      elucidate this synergistic activity, Northern blot analysis was done to study the
      effect of 1,25(OH)2D3 on BMP3 mRNA expression. Several human cell lines (MNNG, U
      2OS, MG-63, KHOS, TE85, HOS) and HBMSC were treated by 1,25(OH)2D3 (10(-8) M for
      24 h). Purified mRNA from treated and untreated cells were denatured using
      glyoxal and dimethylsulfoxide, and were fractionated on a 1% agarose gel. After
      electrophoresis, RNA were blotted onto a nylon membrane and incubated with 32P
      labeled BMP3 and GAPDH riboprobes. Northern blot analysis revealed that, the BMP3
      mRNA level was increased in a few cell lines (MG-63, HBMSC, HOS) after the
      addition of 1,25(OH)2D3 when compared to the untreated cells (127%+/-1; 130.5%+/
      19.5; 207%+/-14). An higher stimulation was observed in HBMSC primary culture
      when compared to differentiated HBMSC. In view of these results, we now
      investigate the following hypothesis: does the BMP3 promoter exhibit the vitamin
      D receptor response like the osteocalcin gene?

PMID- 10088720
TI  - CD44 is not an adhesive receptor for osteopontin.
AB  - Osteopontin is a secreted glycoprotein with adhesive and migratory functions.
      Cellular interactions with osteopontin are mediated through integrin receptors
      which recognize the RGD domain. Recently, CD44, a non-integrin, multifunctional
      adhesion molecule was identified as an osteopontin receptor. CD44 is a ubiquitous
      surface molecule that exists as a number of different isoforms, generated by
      alternative splicing. To analyze which forms of CD44 mediate binding to
      osteopontin, we used the standard form of CD44 as CD44-human immunoglobulin
      fusion proteins and several splice variants in enzyme-linked immunosorbant
      assays. Multiple preparations of osteopontin were used including native
      osteopontin derived from smooth muscle cells, human urinary osteopontin, full
      length recombinant osteopontin, and two recombinant osteopontin fragments
      expected to be formed following thrombin cleavage. Our data show that although
      the CD44-hlg fusion proteins could interact with hyaluronic acid as expected,
      there was no interaction between CD44H, CD44E, CD44v3,v8-v10, or CD44v3 with
      osteopontin. These studies suggest that CD44-osteopontin interactions may not be
      common in vivo and may be limited to a specific CD44 isoform(s), and/or a
      particular modified form of osteopontin.

PMID- 10088721
TI  - In vivo and in vitro association of 14-3-3 epsilon isoform with calmodulin:
      implication for signal transduction and cell proliferation.
AB  - Using a yeast two-hybrid screen, human 14-3-3 epsilon protein was found to
      interact with human calmodulin. In vitro binding assay between human 14-3-3
      epsilon protein/peptide and calmodulin was demonstrated by native gel
      electrophoresis, and the interaction was shown to be calcium dependent. Our
      results, along with the association of the 14-3-3 epsilon protein with other
      signaling proteins, suggest that the 14-3-3 protein could provide a link between
      signal transduction and cell proliferation.

PMID- 10088722
TI  - Prostaglandin E2 stimulates the formation of mineralized bone nodules by a cAMP
      independent mechanism in the culture of adult rat calvarial osteoblasts.
AB  - The effects of prostaglandin E2 (PGE2) on the proliferation and differentiation
      of osteoblastic cells were studied in osteoblast-like cells isolated from adult
      rat calvaria. Treatment of the cells with PGE2 within the concentration range 10(
      8)-10(-5) M resulted in a dose-dependent increase in alkaline phosphatase (ALP)
      activity, [3H]proline incorporation into collagenase-digestible protein, and
      mineralized bone nodule (BN) formation, as well as a dose-dependent decrease in
      [3H]thymidine incorporation into the cells. PGE2 also caused a dose-dependent
      increase in the intracellular cyclic adenosine monophosphate (cAMP) content, with
      a maximal effective concentration of 10(-5) M; this effect of PGE2 was mimicked
      by forskolin, an adenylate cyclase activator. The treatment of adult calvarial
      cells with forskolin decreased BN formation, ALP activity, and collagen
      synthesis. These results suggested that cAMP does not have a stimulatory, but
      rather a suppressive, effect on the differentiation of adult rat calvarial cells.
      A time-course study of cAMP accumulation showed that both PGE2- and forskolin
      induced cAMP reached a maximum at 5 min after the treatment, but the former
      rapidly returned to the basal level by 40 min, while the latter declined slowly
      and was still at 70% of the maximal level at 60 min, suggesting that PGE2
      activates phosphodiesterase as well as adenylate cyclase. The presence of N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist,
      reduced the rate of degradation of cAMP formed after PGE2 treatment, suggesting
      the involvement of calmodulin in the activation of phosphodiesterase. However,
      PGE2 also caused the production of inositol 1,4,5-triphosphate (IP3) and an
      elevation of the intracellular Ca2+ concentration ([Ca2+]i), both of which peaked
      at 15 s and returned to the basal level within 1 min. Submaximal responses of the
      IP3 production and the [Ca2+]i elevation to PGE2 were obtained at 10(-5) M. W-7
      decreased both basal and PGE2-induced ALP activity, collagen synthesis and BN
      formation, indicating the involvement of Ca2+/calmodulin-dependent protein kinase
      in the PGE2-induced differentiation of calvarial cells. From these results, we
      concluded that PGE2 inhibits the proliferation and stimulates the differentiation
      of calvarial osteoblasts by elevating the [Ca2+]i through the activation of a
      phosphoinositide turnover, but not via an activation of adenylate cyclase. We
      also found that BN formation varies, depending on the time of PGE2 addition,
      suggesting that responsiveness of the cells to PGE2 may change during the culture
      period.

PMID- 10088723
TI  - Identification of epithelial and myeloid-specific DNA elements regulating MRP14
      gene transcription.
AB  - Macrophage migration inhibition factor-related protein 14 (MRP14) is a Ca2+
      binding protein of the S-100 family highly abundant in myelomonocytic and
      epithelial cells. The expression pattern is restricted to myeloid and epithelial
      cells and therefore the MRP14 gene is ideally suited to study the regulation of
      gene expression in these cells. We characterized the human MRP14 promoter by
      using the chloramphenicol acetyltransferase reporter assay system. The analysis
      was performed in epithelial (TR146) and myeloid (HL-60) cells, and we were
      successful in mapping positive and negative regulatory elements. The region -114/
      419 contains strong myeloid-specific regulatory elements, whereas the domain 
      600/-1000 enhances the MRP14 transcription in epithelial cells. The sequence 
      462/-600 accommodates a regulatory element that enhances the promoter activity in
      both myeloid and epithelial cells. Regions -114/-419 and -1000/-4500 reduce the
      expression of MRP14 only in epithelial cells, whereas the domains -419/-462 and 
      4500/-6500 contain down-regulating elements in both, epithelial and myeloid
      cells. The presented data demonstrate that transcription of the human MRP14 gene
      is regulated in a complex manner enabling the precise control of the MRP14 level
      in epithelial and myeloid cells.

PMID- 10088724
TI  - Regulatory domain of human heat shock transcription factor-2 is not regulated by
      hemin or heat shock.
AB  - Heat shock transcription factor 2 (HSF-2) activates transcription of heat shock
      proteins in response to hemin in the human erythroleukemia cell line, K562. To
      understand the regulation of HSF-2 activation, a series of deletion mutants of
      HSF-2 fused to the GAL-4 DNA binding domain were generated. We have found that
      human HSF-2 has a regulatory domain located in the carboxyl-terminal portion of
      the protein which represses the activity of its activation domain under normal
      physiological conditions. The repressive effects of this domain can be eliminated
      by its deletion in GAL4-HSF-2 fusion constructs. The regulatory domain of HSF-2
      can also repress a heterologous chimeric activator that contains a portion of the
      VP16 activation domain. The activation domain of HSF-2 is a segment of
      approximately 77 amino acids located proximal to the carboxyl-terminal
      hydrophobic heptad repeat (leucine zipper 4) of the molecule. Interestingly, the
      GAL4-HSF-2 fusion protein and the 77 amino acids activation domain are inactive
      and are not activated by pretreatment of cells with either hemin or elevated
      temperature. Our data suggest that regulation of HSF-2 differs from HSF-1 in that
      its regulatory domain is not responsive to hemin or heat directly.

PMID- 10088725
TI  - Peroxisome targeting of porcine 17beta-hydroxysteroid dehydrogenase type IV/D
      specific multifunctional protein 2 is mediated by its C-terminal tripeptide AKI.
AB  - The product of the porcine HSD17B4 gene is a peroxisomal 80 kDa polypeptide
      containing three functionally distinct domains. The N-terminal part reveals
      activities of 17beta-estradiol dehydrogenase type IV and D-specific 3-hydroxyacyl
      CoA dehydrogenase, the central part shows D-specific hydratase activity with
      straight and 2-methyl-branched 2-enoyl-CoAs. The C-terminal part is similar to
      sterol carrier protein 2. The 80 kDa polypeptide chain ends with the tripeptide
      AKI, which resembles the motif SKL, the first identified peroxisome targeting
      signal PTS1. So far AKI, although being similar to the consensus sequence PTS1,
      has neither been reported to be present in mammalian peroxisomal proteins, nor
      has it been shown to be functional. We investigated whether the HSD17B4 gene
      product is targeted to peroxisomes by this C-terminal motif. Recombinant human
      PTS1 binding protein Pex5p interacted with the bacterially expressed C-terminal
      domain of the HSD17B4 gene product. Binding was competitively blocked by a SKL
      containing peptide. Recombinant deletion mutants of the C-terminal domain lacking
      3, 6, and 14 amino acids and presenting KDY, MIL, and IML, respectively, at their
      C-termini did not interact with Pex5p. The wild-type protein and mutants were
      also transiently expressed in the HEK 293 cells. Immunofluorescence analysis with
      polyclonal antibodies against the C-terminal domain showed a typical punctate
      peroxisomal staining pattern upon wild-type transfection, whereas all mutant
      proteins localized in the cytoplasm. Therefore, AKI is a functional PTS1 signal
      in mammals and the peroxisome targeting of the HSD17B4 gene product is mediated
      by Pex5p.

PMID- 10088726
TI  - Characterization of caspase proteases in cytokine-dependent myeloid progenitor
      cells using enzyme affinity labeling.
AB  - Bone marrow-derived myeloid progenitor cells are dependent on the presence of
      cytokines such as interleukin-3 (IL-3) for their survival. The withdrawal of IL-3
      from IL-3-dependent myeloid progenitors results in death via an apoptotic
      program. Previous studies have shown that IL-3 withdrawal induces the activities
      of caspase proteases. However, the molecular identities of myeloid progenitor
      caspases have not been determined. In this study, we used an affinity labeling
      reagent (biotin-YVAD-acyloxymethyl ketone) that binds to processed active caspase
      subunits, to study caspase activation in 32D and FDCP-1 myeloid progenitor cells.
      After IL-3 withdrawal, we detected affinity labeling of caspase subunits of 20,
      17, and 16 kDa in both cell lines. Surprisingly, affinity labeling of the 20- and
      17-kDa proteins, but not the 16-kDa protein, was also detected in healthy cells
      maintained in the presence of IL-3. By contrast, in cytokine-independent cell
      lines, affinity labeling of caspase subunits was detected only after treatment
      with an apoptotic stimulus. Immunoblotting experiments showed that caspase-3
      constitutes at least a portion of the 20- and 17-kDa affinity-labeled proteins
      detected in the myeloid progenitor cell lines. Taken together, these data provide
      direct evidence of caspase activation in cytokine-dependent myeloid progenitors,
      and suggest that unique apoptotic pathways may exist in these cells.

PMID- 10088727
TI  - Inactivation of MED-1 elements in the TATA-less, initiator-less mouse thymidylate
      synthase promoter has no effect on promoter strength or the complex pattern of
      transcriptional start sites.
AB  - The mouse thymidylate synthase (TS) promoter is a member of a family of promoters
      that lack a TATA box as well as an initiator element and that initiate
      transcription at many sites over a broad initiation window. An element (MED-1)
      downstream of the initiation window of almost all promoters of this family has
      been proposed to be important for promoter activity, as well as for multiple
      start site utilization. Two consensus MED-1 elements are located downstream of
      the initiation window of the TS promoter. To determine the role of the MED-1
      elements in the TS promoter, one or both elements were inactivated by site
      directed mutagenesis and the effects on promoter function were determined. We
      found that inactivation of the MED-1 elements had no measurable effect on
      promoter strength, the boundaries of the initiation window, or the pattern of
      transcriptional start sites. Furthermore, inactivation of the elements did not
      affect the ability of the TS promoter to direct S phase-specific expression of
      the gene in growth-stimulated cells. We conclude that the MED-1 element does not
      play a significant role in TS promoter function and therefore is not an essential
      component of all TATA-less promoters with complex transcriptional initiation
      patterns.

PMID- 10088728
TI  - Differentiation and apoptosis of neuroblastoma cells: role of N-myc gene product.
AB  - To clarify the role and function of the N-myc product in cell differentiation and
      apoptosis, we used the antisense oligonucleotide technique to inhibit N-myc gene
      expression in neuroblastoma cells with different phenotypes: intermediate (I) and
      neuronal (N), or Schwann-glia (S), respectively. The results suggest that N-myc
      operates along different pathways. Inhibiting N-myc gene expression either
      results in suppression of cell proliferation or in induction of differentiation
      and/or apoptosis.

PMID- 10088729
TI  - 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25
      dihydroxyvitamin D3, is a potent suppressor of parathyroid hormone secretion.
AB  - 1Alpha,25(OH)2D3 is an important negative regulator of parathyroid hormone (PTH)
      gene transcription. In parathyroid cells, as in other target tissues,
      1alpha,25(OH)2D3 is degraded by side chain oxidation by the inducible 24
      hydroxylase. We have previously shown that one metabolite of this pathway,
      1alpha,23(S),25-(OH)3-24-oxo-D3, potently suppresses PTH synthesis and secretion
      in cultured bovine parathyroid cells (bPTC). Further examination of the
      metabolites of 1alpha,25(OH)2D3 in bPTC has revealed another compound that is
      less polar than 1alpha,25(OH)2D3. By HPLC analysis and mass spectrometry, this
      metabolite was identified as 1alpha,25(OH)2-3-epi-D3. The activity of this
      metabol ite on PTH gene transcription was assessed by the steady-state PTH
      secretion by bPTC after 72-h treatment with concentrations from 10(-11) M to 10(
      7) M. 1Alpha,25(OH)2-3-epi-D3 was found to be only slightly, but not
      significantly, less active than the native 1alpha,25(OH)2D3 in suppressing PTH
      secretion despite having 30 times lower affinity for the bPTC VDR. Both
      1alpha,25(OH)2D3 and 1alpha,25(OH)2-3-epi-D3 maximally suppressed PTH secretion
      by 50%. Along with 1alpha,25(OH)2-3-epi-D3, the activities of the other two A
      ring diastereomers were assessed. 1beta,25(OH)2D3 suppressed PTH only at 10(-7) M
      with a decrease of only 30%, in good agreement with its low VDR affinity.
      Surprisingly, 1beta,25(OH)2-3-epi-D3 stimulated PTH secretion by 30-50% at
      concentrations from 10(-11) M to 10(-8)M and fell to control (untreated) rates at
      10(-7) M. The mechanism for this increase in PTH secretion is under
      investigation. Metabolism studies performed in bPTC cells using high
      concentrations of 1alpha,25(OH)2D3 substrate showed that in some incubations, the
      concentration of 1alpha,25(OH)2-3-epi-D3 was even higher than that of the parent
      substrate 1alpha,25(OH)2D3. This finding indicates a slower rate of metabolism
      for this diastereomer. Thus, production and accumulation of 1alpha,25(OH)2-3-epi
      D3, as a major stable metabolite of 1alpha,25(OH)2D3 in parathyroid glands, may
      contribute to the prolonged suppressive effect of 1alpha,25(OH)2D3 on PTH gene
      transcription.

PMID- 10088730
TI  - Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and
      transforming growth factor beta1 in C2C12 myogenic cells coincides with
      suppression of the myogenic phenotype but is not sufficient for osteoblast
      differentiation.
AB  - The bone morphogenetic protein (BMP)-2 is a potent osteoinductive signal,
      inducing bone formation in vivo and osteoblast differentiation from non-osseous
      cells in vitro. The runt domain-related protein Cbfa1/PEBP2alphaA/AML-3 is a
      critical component of bone formation in vivo and transcriptional regulator of
      osteoblast differentiation. To investigate the relationship between the
      extracellular BMP-2 signal, Cbfa1, and osteogenesis, we examined expression of
      Cbfa1 and osteoblastic genes during the BMP-2 induced osteogenic
      transdifferentiation of the myoblastic cell line C2C12. BMP-2 treatment
      completely blocked myotube formation and transiently induced expression of Cbfa1
      and the bone-related homeodomain protein Msx-2 concomitant with loss of the
      myoblast phenotype. While induction of collagen type I and alkaline phosphatase
      (AP) expression coincided with Cbfa1 expression, Cbfa1 mRNA was strikingly
      downregulated at the onset of expression of osteopontin (OPN) and osteocalcin
      (OCN) genes, reflecting the mature osteoblast phenotype. TGF-beta1 treatment
      effectively suppressed myogenesis and induced Cbfa1 expression but was
      insufficient to support osteoblast differentiation reflected by the absence of
      ALP, OPN, and OCN. We addressed whether induction of Cbfa1 in response to BMP-2
      results in the transcriptional activation of the OC promoter which contains three
      enhancer Cbfa1 elements. Transfection studies show BMP-2 suppresses OC promoter
      activity in C2C12, but not in osteoblastic ROS 17/2.8 cells. Maximal suppression
      of OC promoter activity in response to BMP-2 requires sequences in the proximal
      promoter (up to nt -365) and may occur independent of the three Cbfa sites. Taken
      together, our results demonstrate a dissociation of Cbfa1 expression from
      development of the osteoblast phenotype. Our findings suggest that Cbfal may
      function transiently to divert a committed myoblast to a potentially osteogenic
      cell. However, other factors induced by BMP-2 appear to be necessary for complete
      expression of the osteoblast phenotype.

PMID- 10088731
TI  - Dual reporter systems in yeast and mammalian cells for assessing progesterone
      receptor modulators.
AB  - In the present study we describe the set-up of a new one-hybrid reporter gene
      assay in Saccharomyces cerevisiae composed of the human progesterone receptor
      fused to the DNA-binding domain of the yeast transcriptional activator Gal4. This
      assay allows the convenient estimation of receptor mediated progestogenic as well
      as antiprogestogenic actions of compounds. The induction of the beta
      galactosidase reporter gene expression correlated well with the progesterone
      receptor affinity and the concentration of the progestins tested. The results
      corresponded to those obtained from a reporter gene assay in the cancer cell line
      CV-1 and in vitro binding experiments using rabbit uterus cytosol. In both the
      yeast and CV-1 cells the activity of antiprogestins was detectable by inhibition
      of the progestin-induced reporter gene expression. Secondary reporter genes under
      the transcriptional control of receptor unrelated promoters have been introduced
      into yeast and mammalian test strains to distinguish between specific receptor
      mediated antihormone actions and nonspecific effects on cellular metabolism.

PMID- 10088732
TI  - Effects of estradiol on aldosterone secretion in ovariectomized rats.
AB  - The effects and action mechanisms of estradiol on aldosterone secretion in female
      rats were studied. Replacement of estradiol benzoate (EB) increased the levels of
      plasma estradiol and aldosterone in ovariectomized (Ovx) rats. The aldosterone
      release from zona glomerulosa (ZG) cells was higher in EB-treated rats than in
      oil-treated animals. EB treatment potentiated the responses of aldosterone
      release to adrenocorticotropic hormone (ACTH), forskolin (FSK), and 8
      bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Administration of EB in
      vivo did not alter cAMP production in response to ACTH or FSK. Although
      angiotensin II (Ang II) increased aldosterone secretion by rat ZG cells, the
      stimulatory effect of Ang II on the release of aldosterone was not altered by EB
      treatment. The conversions of [3H]-deoxycorticosterone to [3H]-corticosterone and
      [3H]-corticosterone to [3H]-aldosterone in EB-treated groups were greater than
      those in the oil-treated group. These results suggest that estradiol increases
      aldosterone secretion in part through the mechanisms involving the activation of
      the post-cAMP pathway, 11beta-hydroxylase and aldosterone synthase activity.

PMID- 10088733
TI  - Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to
      severe ocular inflammation after cataract surgery: a randomized, vehicle
      controlled clinical trial.
AB  - PURPOSE: To investigate the efficacy and safety of ketorolac tromethamine 0.5%
      ophthalmic solution (Acular; Allergan, Inc, Irvine, California) in the treatment
      of moderate to severe anterior segment inflammation developing after unilateral
      cataract surgery with intraocular lens implantation. METHODS: Only patients who
      exhibited moderate or greater levels of cells and flare 1 day after surgery were
      included in this multicenter, double-masked, randomly assigned, parallel-group
      study. Topical ketorolac or vehicle solution (Allergan, Inc) was administered to
      the treated eye four times daily, starting the day after surgery and continuing
      for 14 days. RESULTS: Ketorolac was significantly more effective than the vehicle
      solution in reducing anterior chamber cells (P < or = .030) and flare (P < or =
      .025), conjunctival erythema (P < or = .046), ciliary flush (P < or = .006),
      tearing (P < or = .012), photophobia (P < or = .014), and pain (P < or = .049).
      Half as many patients from the ketorolac group (14/51) were discontinued from the
      study for lack of efficacy, compared with the vehicle group (28/51; P = .005).
      There was no significant difference between ketorolac and the vehicle solution in
      changes in visual acuity, intraocular pressure, biomicroscopic or ophthalmoscopic
      variables, or adverse events. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic
      solution is safe and provides substantial anti-inflammatory activity in the
      treatment of moderate to severe anterior segment inflammation developing after
      cataract surgery and intraocular lens implantation.

PMID- 10088734
TI  - Effect of astigmatic keratotomy on spherical equivalent: results of the
      Astigmatism Reduction Clinical Trial.
AB  - PURPOSE: To determine the effect of astigmatic keratotomy on spherical
      equivalent, as measured by the coupling ratio and a new quantity, coupling
      constant. METHODS: In a prospective multicenter study, subjects underwent arcuate
      keratotomy at a 7-mm optical zone by means of the Lindstrom nomogram for
      correction of astigmatism. One hundred fifty-seven eyes of 95 patients who had a
      follow-up examination 1 month postoperatively were studied. Mean preoperative
      refractive cylinder +/- SEM was 2.82 +/- 1.17 diopters. Coupling ratio was
      defined as the ratio of the flattening of the incised meridian to the steepening
      of the opposite meridian. Coupling constant was defined as the ratio of the
      change in spherical equivalent to the magnitude of the vector change in
      astigmatism. Coupling ratio, coupling constant, and change in spherical
      equivalent were calculated on the basis of change in refraction and keratometry.
      RESULTS: On the basis of change in refraction, coupling ratio was 0.95 +/- 0.10
      (mean +/- SEM) and coupling constant was -0.01 +/- 0.03, consistent with a minor
      shift in the spherical equivalent of -0.03 +/- 0.07 diopter. On the basis of
      change in keratometry, coupling ratio was 0.84 +/- 0.05 and coupling constant was
      -0.04 +/- 0.02, consistent with minor postoperative keratometric steepening of 
      0.10 +/- 0.04 diopter. Coupling ratio based on change in refraction was not
      statistically different from the coupling ratio predicted by the Gauss' law for
      inelastic domes (P = .370). Incision length and number, amount of achieved
      cylinder correction, age, and sex had no statistically significant effect on
      coupling ratio, coupling constant, and change in spherical equivalent.
      CONCLUSIONS: Cornea behaved as an inelastic surface in response to arcuate
      keratotomy performed with the Astigmatism Reduction Clinical Trial study
      nomogram. On average, astigmatic keratotomy had a minimal effect on spherical
      equivalent refraction. There was variability, however, in coupling ratio,
      coupling constant, and change in spherical equivalent from eye to eye after
      astigmatic keratotomy. Caution is therefore advised when simultaneous correction
      of cylinder and spherical equivalent is planned.

PMID- 10088735
TI  - Retinal detachment in phakic eyes with anterior chamber intraocular lenses to
      correct severe myopia.
AB  - PURPOSE: To analyze the incidence and characteristics of retinal detachment in
      patients with severe myopia corrected by implantation of phakic anterior chamber
      intraocular lenses. METHODS: We studied retinal detachments in 166 consecutive
      eyes (98 patients) that underwent implantation of angle-supported phakic anterior
      chamber intraocular lenses (models ZB5M and ZB5MF; Domilens; Lyon, France) for
      the correction of severe myopia (follow-up +/- SD, 45.26 +/- 14.65 months; range,
      20 to 84 months). RESULTS: Retinal detachment occurred in eight eyes (4.8%); four
      eyes belonged to men and four to women. The time between implanting surgery and
      retinal detachment was 17.43 +/- 16.4 months (range, 1 to 44 months). In all
      cases, retinal detachment was spontaneous. In seven eyes, the retina was
      reattached successfully during the first retinal detachment surgery. Mean best
      corrected visual acuity after phakic anterior chamber intraocular lens
      implantation and before retinal detachment development was 20/50 (range, 20/100
      to 20/25). After retinal detachment repair, best-corrected visual acuity was
      20/73 (range, 20/2000 to 20/33). In these seven eyes, differences between best
      corrected visual acuity before and after reattachment were not statistically
      significant (P = .898, paired Student t test). In one eye, a proliferative
      vitreoretinopathy was observed, which required additional treatment by vitrectomy
      and explantation of the phakic anterior chamber intraocular lens. A refractive
      change was observed after retinal detachment repair, from -1.1 +/- 0.7 diopters
      (range, 0.00 to -2.50 diopters) before retinal detachment and -2.8 +/- 1.1
      diopters (range, -1.00 to -4.50 diopters) after retinal detachment surgery (P =
      .03, paired Student t test). CONCLUSIONS: The implantation of a phakic anterior
      chamber intraocular lens as a correcting procedure for severe myopia was followed
      by a 4.8% incidence of retinal detachment. Conventional scleral surgery was
      successful in most cases, without causing significant changes in the final best
      corrected visual acuity. A significant increase in the myopic spherical
      equivalent was observed after retinal detachment repair in these patients.

PMID- 10088736
TI  - Treatment of recurrent cytomegalovirus retinitis with the ganciclovir implant.
AB  - PURPOSE: To evaluate preoperative characteristics and outcome of the treatment of
      recurrent cytomegalovirus (CMV) retinitis with the ganciclovir implant. METHODS:
      Records of 54 patients with acquired immunodeficiency syndrome and active,
      previously treated CMV retinitis who received a ganciclovir implant in one (n =
      31) or both (n = 23) eyes were reviewed. Entry criteria included prior insertion
      and removal of an indwelling catheter or failure to respond to tolerated doses of
      ganciclovir and foscarnet. Preoperative factors that might correlate with outcome
      were analyzed, including demographic factors, duration of human immunodeficiency
      virus disease and CMV retinitis, indications for surgery, prior anti-CMV
      treatment, and extent of retinitis. RESULTS: Forty-six patients completed 1 month
      of follow-up and were analyzed for outcome. Thirty-one (67.4%) had inactive
      retinitis at 1 month vs 15 (32.6%) with active retinitis, and they received a
      mean of 23.5 +/- 22.9 weeks of preoperative ganciclovir vs 58.0 +/- 52.0 weeks in
      patients with active retinitis (P = .003). Involvement of more than 25% of
      retinal area by CMV retinitis was also correlated with activity at 1 month (P <
      .001). Patients who received implants because of lack of venous access had a
      median time to progression of 8.0 +/- 3.0 months vs 2.0 +/- 1.2 months for
      patients who had inadequate response or intolerance to intravenous medication (P
      = .073). Patients with 6 months or less vs more than 6 months of preoperative
      ganciclovir treatment had progression at a median time of 8.0 +/- 1.7 months vs
      2.0 +/- 0.3 months, respectively (P = .016). CONCLUSION: Longer duration of
      preoperative ganciclovir or larger area of CMV retinitis correlates with lower
      success of ganciclovir implant therapy for recurrent retinitis.

PMID- 10088737
TI  - Effect of potent antiretroviral therapy on recurrent cytomegalovirus retinitis
      treated with the ganciclovir implant.
AB  - PURPOSE: To determine the effect of highly active antiretroviral therapy on
      cytomegalovirus (CMV) retinitis treated with ganciclovir implants. METHODS: A
      retrospective cohort study was performed of 15 patients with recurrent CMV
      retinitis treated with the ganciclovir implant and highly active antiretroviral
      therapy (cases) and 38 patients with recurrent retinitis treated with ganciclovir
      implants before availability of improved antiretroviral therapy (controls).
      Progression was defined as occurrence of new lesions in the treated eye or
      advancement of the retinitis border by more than 750 microm. RESULTS: Cases and
      controls were statistically similar in age, ethnicity, and duration of acquired
      immunodeficiency syndrome (AIDS). Controls had received intravenous ganciclovir
      for 9.5 +/- 9.5 months vs 3.5 +/- 4.6 months in cases (P = .003). The mean (+/-
      SE) time to progression of retinitis after implantation of the device was 26.7 +/
      2.4 months (95% confidence interval, 22.1 to 31.3) in the cases receiving highly
      active antiretroviral therapy vs 6.2 +/- 0.9 months (95% confidence interval, 4.5
      to 7.9) in the controls (P = .001). Multivariate analysis, adjusted for
      preoperative variables, confirmed a significantly prolonged time to progression
      in patients receiving highly active antiretroviral therapy (P = .0003). The odds
      ratio for progression in the cases vs controls was 0.034 (95% confidence
      interval, 0.003 to 0.350). Cases had higher CD4+ T-lymphocyte counts (P = .004)
      and longer survival (P < .001) than controls. CONCLUSION: Highly active
      antiretroviral therapy is associated with improved outcomes in patients with AIDS
      and recurrent CMV retinitis treated with the ganciclovir implant.

PMID- 10088738
TI  - Visual and anatomic outcomes associated with posterior segment complications
      after ganciclovir implant procedures in patients with AIDS and cytomegalovirus
      retinitis.
AB  - PURPOSE: To determine anatomic and visual acuity outcomes of posterior segment
      complications after ganciclovir implant surgery. METHODS: We reviewed the medical
      records of 63 patients with acquired immunodeficiency syndrome who had active
      cytomegalovirus retinitis in 82 eyes and who underwent 110 consecutive
      ganciclovir implant procedures. Preoperative and postoperative visual acuity,
      type of postoperative complication, treatment, and lines of visual acuity change
      were determined. RESULTS: Thirty-eight eyes of 19 patients had bilateral
      ganciclovir implant procedures, and 25 eyes of 19 patients underwent two or more
      ganciclovir implant procedures. Thirteen (12%) of 110 ganciclovir implant
      procedures developed posterior segment complications: rhegmatogenous retinal
      detachment in six, vitreous hemorrhage in four, endophthalmitis in two, and
      cystoid macular edema with epiretinal membrane in one. Treatment included pars
      plana vitrectomy with silicone oil in two cases and without silicone oil in three
      cases, scleral buckling in one, intravitreal antibiotic injection in two, and
      laser photocoagulation in two. Overall, median visual acuity was 20/25
      preoperatively. Median follow-up was 6 months for all eyes and 7 months for eyes
      with complications. Postoperative median visual acuity was 20/25 for eyes without
      complications vs 20/40 at 1 month, 20/60 at 3 and 6 months, and 20/100 at 12
      months in eyes with complications (P < .001). More eyes with than without
      complications lost 2 or more lines of visual acuity (P < .001). CONCLUSION:
      Postoperative complications occurred in 12% of the ganciclovir implant procedures
      and were associated with decreased visual acuity despite treatment.

PMID- 10088739
TI  - Intraocular anti-Toxoplasma gondii IgA antibody production in patients with
      ocular toxoplasmosis.
AB  - PURPOSE: To investigate the immunoglobulin classes associated with the
      intraocular anti-Toxoplasma gondii antibody response during clinical ocular
      toxoplasmosis and to determine which immunoglobulin class is most helpful in the
      diagnosis of this disease. METHODS: Paired serum and intraocular fluid samples
      from 155 patients who had uveitis were tested for intraocular anti-T. gondii IgG,
      IgA, and IgM antibody production. The presence of T. gondii DNA was determined by
      polymerase chain reaction. Patients were divided into two groups, based on the
      initial clinical diagnosis; group 1 included 78 patients with presumed ocular
      toxoplasmosis, and group 2 included 77 patients with uveitis that was not
      clinically suspected to be ocular toxoplasmosis. Samples from 27 nonuveitis
      patients who underwent intraocular surgery were used as control subjects. The
      final diagnosis was based on the clinical course and interpretation of laboratory
      tests. RESULTS: A final diagnosis of ocular toxoplasmosis was made in 88 of 155
      patients (group 1, 68; group 2, 20). Among these patients, 65% had intraocular
      IgG production, 52% had intraocular IgA production, 37.5% had both IgG and IgA
      production, 27% had IgG production only, and 15% had IgA production only. Of the
      13 patients tested, only one had intraocular IgM production. Intraocular IgA
      could not be detected in patients who had final diagnoses other than ocular
      toxoplasmosis or in control subjects. A positive polymerase chain reaction
      combined with a test that was positive for intraocular IgG production had a
      sensitivity of 77%, which increased to 91% after the detection of intraocular IgA
      production was added. CONCLUSIONS: Immunoglobulin G is the major class involved
      in the humoral immune response against the T. gondii parasite, followed by IgA.
      The determination of IgA production is useful as an additional test in the
      diagnosis of ocular toxoplasmosis.

PMID- 10088740
TI  - Optical coherence tomography of idiopathic polypoidal choroidal vasculopathy.
AB  - PURPOSE: To document and study the cross-sectional structures of polypoidal
      elements using optical coherence tomography in eyes with idiopathic polypoidal
      choroidal vasculopathy. METHODS: Optical coherence tomography images of two eyes
      with idiopathic polypoidal choroidal vasculopathy were correlated with slit-lamp
      biomicroscopic findings, fundus photographs, fluorescein angiograms, and
      indocyanine green angiograms. RESULTS: Cross-sectional optical coherence
      tomographic images of retinochoroidal structures showed prominent anterior
      protrusion of the orange subretinal mass corresponding to the polypoidal
      structure in the indocyanine green angiogram. Hemorrhagic detachment of the
      retinal pigment epithelium was contiguous with the cone-shaped nodule beneath the
      retinal pigment epithelium in one eye, and an apparent discontinuity was observed
      in the highly reflective layer that delineates the polypoidal structure.
      CONCLUSIONS: Some of the polypoidal structures in eyes with idiopathic polypoidal
      choroidal vasculopathy are anteriorly protruding lesions in the inner choroid
      that may cause serosanguineous detachment of the retinal pigment epithelium
      through damage of the overlying Bruch membrane, retinal pigment epithelium, and
      the adhesion between them. Cross-sectional optical coherence tomographic images
      may increase understanding of the pathophysiology of idiopathic polypoidal
      choroidal vasculopathy.

PMID- 10088741
TI  - Macular hole surgery in conjunction with endolaser photocoagulation.
AB  - PURPOSE: To determine whether endolaser photocoagulation to the retinal pigment
      epithelium at the base of a macular hole increases the anatomic success rate of
      surgery. METHODS: In a prospective consecutive clinical trial, eight eyes of
      seven patients with idiopathic macular hole underwent vitrectomy with posterior
      cortical vitreous removal and peeling of visible epiretinal membrane when
      present. A single shot of argon endolaser photocoagulation was applied to the
      retinal pigment epithelium at the center of the macular hole with a duration of
      0.05 to 0.2 seconds and an intensity of 50 to 200 mW. After fluid-gas exchange
      was performed with 14% perfluoropropane gas, patients maintained face-down
      positioning for 2 weeks. RESULTS: One eye with stage 2 macular hole, six eyes
      with stage 3 macular hole, and one eye with stage 4 macular hole were included.
      All eight eyes had a closed macular hole (100% anatomic success rate) at final
      examination 6 to 12 months after surgery. Best-corrected visual acuity improved 3
      or more lines on the Early Treatment Diabetic Retinopathy Study visual acuity
      chart in all eyes. Four (50%) of the eight eyes had a final visual acuity of
      20/40 or better. CONCLUSIONS: Endolaser photocoagulation may be a useful adjunct
      to macular hole surgery but requires further investigation and long-term
      evaluation.

PMID- 10088742
TI  - Automated perimetry in amblyopia: a generalized depression.
AB  - PURPOSE: To quantitate the visual field abnormalities associated with amblyopia.
      METHODS: In a prospective study, 37 amblyopic patients (11 anisometropic, 13
      strabismic, 9 combination, 4 deprivation) performed automated perimetry in each
      eye using the Humphrey 30-2 program. Primary outcome measures were foveal
      threshold, mean deviation, and average threshold. RESULTS: When the probability
      plots were examined, 21 visual fields in amblyopic eyes were normal, 8 had
      central scotomas, and 7 had diffuse depressions. No focal defects other than mild
      central scotomas were seen. However, the foveal threshold of amblyopic eyes was
      decreased by an average of 7.2 +/- 8.0 dB (P < .0001) compared with fellow eyes;
      intereye differences in mean deviation (3.2 +/- 5.4 dB; P < .001) and average
      threshold (2.9 +/- 5.3 dB; P < .005) were also seen. This decrease in sensitivity
      for the amblyopic eye occurred for all types of amblyopia. The depression in
      threshold was greatest at the fovea but was detectable and significant at all
      eccentricities of the 30-degree field. The average threshold in the amblyopic eye
      was highly correlated with visual acuity (r = .839; P < .001). CONCLUSIONS:
      Although automated visual fields in amblyopic eyes typically appear normal, all
      four types of amblyopia are associated with a generalized depression of light
      sensitivity, which is proportionately greatest at the fovea and highly correlated
      with visual acuity loss. In general, amblyopia is not associated with any area of
      focal loss of threshold light sensitivity. If a focal defect is present in the
      visual field of the amblyopic eye, organic causes of visual loss should be
      suspected. The Humphrey visual field analyzer STATPAC program (Allergan-Humphrey,
      Inc, San Leandro, California) may artifactually transform small and generalized
      full-field depressions in a manner that makes them appear to be isolated central
      defects.

PMID- 10088743
TI  - Congenital insensitivity to pain with anhidrosis: ocular and systemic
      manifestations.
AB  - PURPOSE: To report the incidence and severity of the ophthalmologic
      manifestations in patients with congenital insensitivity to pain with anhidrosis.
      METHODS: Fifteen Bedouin children with congenital insensitivity to pain with
      anhidrosis underwent complete ocular examination, including refraction and
      assessment of corneal sensation, and a detailed neurologic examination, including
      measurement of median nerve motor and sensory conduction. Patients with corneal
      ulcers were treated appropriately. RESULTS: In the 15 children (eight girls and
      seven boys, with a mean age of 3.75 +/- 2.67 years; range, 9 months to 9 years),
      corneal sensation was absent in both eyes. Corneal opacities were present in 10
      children, five of whom had bilateral corneal opacities. Corneal ulcers were found
      in seven children, two of whom had bilateral ulcers, and in three children the
      ulcers recurred. The corneal ulcers were characterized by very poor healing. The
      surgical procedures included four lateral tarsorrhaphies, two corneal patch
      grafts, and one penetrating keratoplasty. All the patients had self-inflicted
      injuries varying from skin ulcers, burns, and bone fractures to autoamputations
      of fingertips and tongues. Many patients showed delayed healing and repair of
      bone and skin injuries. All patients had attacks of hyperpyrexia, moderate mental
      retardation, and hypotonicity with absent superficial sensation to light touch.
      Results of median nerve motor and sensory conduction studies were within normal
      limits. CONCLUSIONS: The patients with congenital insensitivity to pain and
      anhidrosis and absent corneal sensation showed a marked tendency to develop
      corneal ulcers that healed poorly. Congenital insensitivity to pain and
      anhidrosis, although rare, should be considered in the differential diagnosis of
      neurotrophic keratitis.

PMID- 10088744
TI  - Therapeutic decisions: informed choices in a changing clinical environment.

PMID- 10088745
TI  - Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in
      the era of potent antiretroviral therapy: recommendations of the International
      AIDS Society-USA panel.
AB  - PURPOSE: To describe the risks, benefits, and recommended use of the ganciclovir
      implant for the treatment of human immunodeficiency virus-related cytomegalovirus
      (CMV) retinitis in the era of potent antiretroviral therapy. METHODS: A panel of
      physicians with expertise in the use of the ganciclovir implant and in the
      management of CMV retinitis was convened by the International AIDS Society-USA.
      The panel reviewed and discussed available data, and developed recommendations
      for the use of the ganciclovir implant, the surgical technique, and related
      management issues. Recommendations were rated according to the strength and
      quality of the supporting evidence. RESULTS: The effect of potent antiretroviral
      therapy on the immunologic status of patients with human immunodeficiency virus
      disease has changed the manifestation and course of CMV retinitis in many
      patients. The clinical management of CMV retinitis and the role of the
      ganciclovir implant are thus changing. Factors in the decision to choose the
      ganciclovir implant include the patient's potential for immunologic improvement,
      location and severity of CMV retinitis, and the risks and costs associated with
      implantation and concomitant oral ganciclovir therapy. CONCLUSIONS: The
      ganciclovir implant is safe and effective for the treatment of CMV retinitis. The
      indications for its use should be modified to account for increased patient
      survival and the potential for CMV retinitis to be controlled by effective
      antiretroviral therapy. Optimal use of the ganciclovir implant and
      discontinuation of therapy in selected patients with improvement in immunity may
      result in better long-term visual outcomes.

PMID- 10088746
TI  - Posterior lamellar keratoplasty for a case of pseudophakic bullous keratopathy.
AB  - PURPOSE: To describe a new surgical technique for posterior corneal
      transplantation. METHODS: An elderly patient had painful, pseudophakic bullous
      keratopathy with low visual potential. Through a 9.0-mm scleral tunnel incision,
      a midstromal pocket was dissected across the cornea, and a posterior lamellar
      disk 7.0-mm in diameter, which consisted of posterior stroma, Descemet membrane,
      and endothelium, was excised. A similarly shaped donor posterior disk was
      implanted in the recipient opening without suture fixation, and the scleral
      incision was sutured. RESULTS: Throughout the postoperative period, the posterior
      corneal transplant remained clear and in position. Three months after surgery,
      the "suture-in" astigmatic error was 3.5 diopters. Pachymetry measured 0.44 mm.
      CONCLUSION: Posterior lamellar keratoplasty may be a new surgical approach with
      which to manage corneal endothelial disorders.

PMID- 10088747
TI  - Stability of vision during space flight in an astronaut with bilateral
      intraocular lenses.
AB  - PURPOSE: To report excellent and stable vision in an astronaut during space
      flight after bilateral cataract surgery with intraocular lenses. METHODS: A 60
      year-old physician mission specialist astronaut developed cataracts and underwent
      phacoemulsification with insertion of one-piece polymethylmethacrylate
      intraocular lenses that had 6-mm optics bilaterally. Several months later, he
      flew on a space shuttle mission. Ocular examinations were performed before and
      after the mission, and the patient was questioned about visual changes during
      flight. RESULTS: Ocular examinations demonstrated stable bilateral posterior
      chamber intraocular lenses. Our subject reported excellent vision during liftoff,
      18 days of microgravity, changes in cabin pressure, and reentry. CONCLUSION:
      Results suggest that intraocular lenses are safe, effective, and well tolerated
      during space flight.

PMID- 10088748
TI  - Complete occlusion of the anterior capsular opening after intact capsulorhexis:
      clinicopathologic correlation.
AB  - PURPOSE: To report histopathologic findings of capsule contraction syndrome with
      complete occlusion of the capsulorhexis opening. METHODS: Case report. In an 81
      year-old woman, a complete occlusion of the anterior capsulorhexis opening
      developed 2 months after phacoemulsification and intraocular lens implantation.
      We surgically removed the contracted anterior capsule and analyzed the membrane
      by standard light microscopy and actin immunohistology. RESULTS: Light
      microscopic analysis of the membrane showed fibrous tissue subcapsularly with
      metaplastic lens epithelial cells. The contracted capsulorhexis opening was
      filled completely with proliferated actin-positive lens epithelial cells.
      CONCLUSIONS: Complete occlusion of the capsulorhexis opening can be attributed to
      excessive shrinkage of the capsule, probably caused by actin filaments found in
      the residual lens epithelial cells together with weak zonular support, and to the
      occlusion of the remaining central defect by massive proliferation of metaplastic
      lens epithelial cells.

PMID- 10088749
TI  - Alcaligenes xylosoxidans endophthalmitis 8 months after cataract extraction.
AB  - PURPOSE: To report a case of Alcaligenes xylosoxidans endophthalmitis and to
      increase awareness of its potential as an intraocular pathogen. METHODS: An 80
      year-old woman in good general health developed A. xylosoxidans endophthalmitis 8
      months after an uncomplicated cataract extraction performed at another
      institution. Eventually, vitrectomy with removal of the intraocular lens and
      capsule was performed because of recurrent disease after intravitreal antibiotic
      injections. RESULTS: Microbiologic examination of the vitreous biopsies and
      capsule disclosed A. xylosoxidans, a motile, gram-negative rod resistant to many
      antibiotics. CONCLUSION: A. xylosoxidans should be considered as a cause of low
      grade endophthalmitis after cataract surgery.

PMID- 10088750
TI  - Recurrent anterior uveitis associated with streptococcal pharyngitis in a patient
      with a history of poststreptococcal syndrome.
AB  - PURPOSE: To provide additional evidence that anterior uveitis can be a
      manifestation of poststreptococcal syndrome. METHOD: A case report providing
      follow-up information on a previously described patient. RESULTS: An adolescent
      girl in whom anterior uveitis was the only manifestation of poststreptococcal
      syndrome subsequently developed recurrent anterior uveitis after another episode
      of streptococcal pharyngitis. CONCLUSION: Anterior uveitis can recur in a manner
      similar to other manifestations of poststreptococcal syndrome after reinfection
      with group A streptococci.

PMID- 10088751
TI  - Coxsackievirus B4 as a cause of adult chorioretinitis.
AB  - PURPOSE: To describe the clinical manifestation and course of chorioretinitis
      presumed to be secondary to coxsackievirus infection in an adult. METHOD: Case
      report documented by fundus photography and fluorescein angiography. RESULTS:
      Ophthalmoscopic examination of a symptomatic 34-year-old woman showed several
      cream-colored parafoveal spots at the level of the retinal pigment epithelium and
      similar, multiple confluent spots in the midperiphery of both eyes. Titers for
      coxsackievirus B4 demonstrated a fourfold rise between acute and convalescent
      sera. CONCLUSION: Coxsackievirus B4 is apparently a rare cause of chorioretinitis
      but nevertheless should be considered in the appropriate clinical setting.

PMID- 10088752
TI  - Potential complication associated with removal of ganciclovir implants.
AB  - PURPOSE: To describe the complication of separation of the medication pellet from
      the tab during the removal of a ganciclovir implant. METHOD: Case reports.
      RESULTS: Separation of the pellet from the tab upon removal of ganciclovir
      implants occurred at the time of reimplantation in two human immunodeficiency
      virus (HIV)-positive patients with cytomegalovirus (CMV) retinitis. CONCLUSIONS:
      Our cases show the possibility of pellet separation from the tab during the
      removal of a ganciclovir implant. Although pellet separation from its tab is
      rare, surgeons should be aware of this potential complication. Modifying
      recommended techniques to remove the ganciclovir implant may reduce the incidence
      of pellet-tab separation.

PMID- 10088753
TI  - Indocyanine green angiographic features in tuberculous chorioretinitis.
AB  - PURPOSE: To determine choroidal involvement in presumed tuberculous posterior
      uveitis by examining indocyanine green angiographic features. METHODS:
      Indocyanine green angiography was performed according to a standard uveitis
      angiographic protocol in eight consecutive patients (15 eyes) with presumed
      posterior tuberculous uveitis. RESULTS: In 100% of the 15 examined eyes,
      indocyanine green angiography disclosed choroidal lesions that were subclinical,
      not detected by fundus examination or fluorescein angiography, in six (40%) of 15
      eyes. Findings were classified into four main angiographic signs: (1) irregularly
      distributed, hypofluorescent areas in the early and intermediate phases of
      angiography that either became isofluorescent (type 1 hypofluorescence) or
      remained hypofluorescent (type 2 hypofluorescence) in the late phase; (2)
      numerous, small, focal, hyperfluorescent spots; (3) choroidal vessels that
      appeared fuzzy in the intermediate phase because of leakage, leading in the late
      phase to (4) diffuse choroidal hyperfluorescence. Type 1 hypofluorescent lesions,
      fuzzy choroidal vessels, and diffuse choroidal hyperfluorescence tended to
      regress after the initiation of antituberculous and corticosteroid treatment.
      Focal hyperfluorescence tended to be associated with longstanding disease.
      CONCLUSIONS: Indocyanine green angiography was useful in assessing and
      quantifying the as yet unknown extent of choroidal involvement in tuberculous
      posterior uveitis. Its characteristic appearance may be a valuable contribution
      to the diagnosis and monitoring of treatment response.

PMID- 10088754
TI  - Bilateral posterior ischemic optic neuropathy after spinal surgery.
AB  - PURPOSE: To report the association between bilateral posterior ischemic optic
      neuropathy and spinal surgery. METHOD: Case report. RESULTS: After prone-position
      spinal surgery of 8 hours' duration, a 68-year-old woman was completely blind in
      both eyes. Moderate periorbital edema and temporal conjunctival chemosis were
      present bilaterally. Ophthalmic examination disclosed normal-appearing optic
      nerve heads, except for bilateral nasal fullness related to bilateral optic nerve
      drusen, and no retinal edema. Immediate cerebral arteriography, magnetic
      resonance imaging, and electroretinography were normal. Visual-evoked response
      was not detectable, and 7 weeks later, severe bilateral optic nerve head pallor
      developed. CONCLUSIONS: Severe selective hypoperfusion of the retrobulbar optic
      nerves may occur after spinal surgery. Pressure to the periorbital region may be
      a contributing factor.

PMID- 10088755
TI  - Ocular malformations, moyamoya disease, and midline cranial defects: a distinct
      syndrome.
AB  - PURPOSE: To report a 10-year-old girl with developmental anomalies of both optic
      disks, a chorioretinal coloboma, sphenopharyngeal meningoencephalocele, and
      moyamoya disease. METHODS: A full ophthalmologic examination, cranial magnetic
      resonance imaging and magnetic resonance angiography, and cerebral angiography
      were performed. RESULTS: The patient had a morning glory disk anomaly and
      microphthalmos of the right eye and optic nerve hypoplasia and retinochoroidal
      coloboma in the left eye. She had a midfacial cleft and an episode of seizures
      and a stroke. Magnetic resonance imaging showed a sphenopharyngeal
      meningoencephalocele. Magnetic resonance angiography and cerebral angiography
      demonstrated a pattern consistent with moyamoya disease. CONCLUSIONS: This
      patient had a distinct syndrome of optic disk, retinochoroidal, and carotid
      circulation anomalies with midline cranial defects. The recognition and treatment
      of the vascular abnormalities and cranial defects may prevent complications such
      as strokes that may occur during or after general anesthesia.

PMID- 10088756
TI  - Exclusion of candidate genetic loci for Duane retraction syndrome.
AB  - PURPOSE: To report preliminary linkage analysis of a large Hispanic family
      showing autosomal dominant inheritance for Duane retraction syndrome. METHODS:
      Microsatellite analysis was used to examine genomic DNA isolated from members of
      a large family with autosomal dominant Duane retraction syndrome for linkage to
      candidate loci for Duane retraction syndrome. Chromosomes 4, 8, and 22 were
      chosen for study because previous reports had documented karyotypic abnormalities
      in unrelated patients with Duane retraction syndrome. RESULTS: No lod scores over
      0.5 were found for markers on chromosomes 4, 8, or 22. This analysis excludes
      these candidate sites. CONCLUSIONS: Studies do not support linkage between Duane
      retraction syndrome in this family and chromosomes 4, 8, and 22. Duane retraction
      syndrome may result from mutations in a heterogeneous group of genes.

PMID- 10088757
TI  - Sinus histiocytosis presenting as bilateral epibulbar masses.
AB  - PURPOSE: To report a case of sinus histiocytosis presenting as multiple,
      bilateral epibulbar masses. METHODS: We examined a 4-year-old child with a 2
      month history of gradually enlarging, salmon-colored epibulbar masses. Excisional
      biopsies and a systemic evaluation were performed. RESULTS: Systemic evaluation
      was normal; no lymphadenopathy was documented. Histopathologic evaluation
      disclosed features consistent with sinus histiocytosis. Flow cytometry and gene
      rearrangement studies confirmed the benign nature of the disease. No tumor
      recurrence was noted. CONCLUSION: Sinus histiocytosis may present as isolated
      epibulbar masses that may be treated with surgical excision.

PMID- 10088758
TI  - Ocular adnexal granulocytic sarcoma as the first sign of acute myelogenous
      leukemia relapse.
AB  - PURPOSE: To report a case of granulocytic sarcoma involving the eyelids and
      caruncles after bone marrow transplantation. METHODS: Case report. A 30-year-old
      man with acute myeloid leukemia in remission developed multiple friable eyelid
      and caruncular lesions in addition to two cutaneous lesions on the chest wall and
      right axilla approximately 3 months after a successful autologous bone marrow
      transplant. RESULT: Pathologic examination was consistent with granulocytic
      sarcoma. CONCLUSION: This condition should be considered in the differential
      diagnosis of cutaneous or eyelid masses in patients with a history of leukemia.

PMID- 10088759
TI  - Genetics and osteoarthritis: exposing the iceberg.

PMID- 10088760
TI  - Y2K, strategic alliances, and you.

PMID- 10088761
TI  - Provision of primary care by office-based rheumatologists: results from the
      National Ambulatory Medical Care Surveys, 1991-1995.
AB  - OBJECTIVE: To determine the extent to which office-based rheumatologists provide
      primary care to patients without rheumatic diseases or provide principal care to
      patients with rheumatoid arthritis (RA). METHODS: The National Ambulatory Medical
      Care Survey was used to determine national probability estimates of the nature
      and types of conditions treated by office-based rheumatologists in 1991-1995. At
      each of 1,074 patient visits, the rheumatologists recorded up to 3 diagnoses and
      3 patient-reported reasons for the visit, as well as information on the
      treatments provided at the visit. RESULTS: In only 9.8% of new consultations and
      11.9% of return visits was neither a rheumatic disease diagnosis nor a
      musculoskeletal complaint recorded, indicating that the rheumatologist was likely
      acting as a primary care provider at a minority of patient visits. Among
      continuing patients with RA, the patient's primary reason for the visit was
      something other than a musculoskeletal complaint in only 9.9% of visits, and any
      nonrheumatic complaint was recorded in 30.4% of visits, indicating that at only
      some visits was the rheumatologist acting as the principal caregiver. In
      addition, only 31.1% of visits included the provision of medication for a
      nonrheumatic condition. CONCLUSION: In 1991-1995, most visits to rheumatologists
      involved the provision of specialized or consultative care to patients with
      rheumatic diseases or musculoskeletal complaints, and few visits were made by
      patients without either indication. Provision of principal care by
      rheumatologists to patients with RA is not currently widespread.

PMID- 10088762
TI  - The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955-1985.
AB  - OBJECTIVE: To describe trends in the epidemiology of rheumatoid arthritis (RA)
      over a period of 30 years in a population-based cohort. METHODS: An inception
      cohort of Rochester, Minnesota residents who were > or =35 years of age and had
      RA (as defined by the 1987 American College of Rheumatology criteria for RA)
      first diagnosed between January 1, 1955 and January 1, 1985 was assembled and
      followed up until January 1, 1995. Incidence rates were age- and sex-adjusted to
      the 1970 US white population. Prevalence of RA in this cohort was estimated on
      January 1, 1985. A birth-cohort analysis was performed by calculating and
      comparing incidence rates in each of 16 birth cohorts. RESULTS: Of the 425
      Rochester residents who fulfilled the inclusion criteria, there were 113 men
      (26.6%) and 312 women (73.4%), with a mean age at diagnosis of 60.2 years. The
      mean followup time was 15.1 years. The overall age- and sex-adjusted annual
      incidence of RA among Rochester, Minnesota residents > or =35 years of age (1955
      1985) was 75.3 per 100,000 population (95% confidence interval 68.0-82.5). This
      incidence was approximately double in women compared with that in men and
      increased steadily with age, until age 85, after which the incidence of RA
      decreased. Secular trends in the incidence of RA over the entire study period
      were demonstrated. The overall prevalence of RA on January 1, 1985 was
      approximately 1%. The birth-cohort analysis showed peak incidence rates in the
      1880-1895 birth cohorts. CONCLUSION: The epidemiology of RA is dynamic. The
      findings in this study lend further support to the hypothesis of a host
      environment interaction in the pathogenesis of RA.

PMID- 10088763
TI  - Microscopic polyangiitis: clinical and laboratory findings in eighty-five
      patients.
AB  - OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings,
      and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in
      various clinical trials conducted by the French Vasculitis Study Group. METHODS:
      A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in
      the study. Seventy-one of them were included in prospective therapeutic trials.
      Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was
      based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/
      SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical
      symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement
      (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%),
      myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar
      hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine
      level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal
      insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis
      at the time of diagnosis, and long-term dialysis was necessary for 10 patients.
      Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients
      (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a
      cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and
      antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked
      immunosorbent assay. Of the 30 patients who underwent renal and celiac
      angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8
      died during or after the relapse. During followup, 28 of the 85 patients (32.9%)
      died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months.
      Deaths were less frequent when patients had been treated with steroids and
      immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15
      patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This
      study demonstrated that MPA is a multisystemic disease in which renal symptoms
      are frequent, but the disease is also associated with general symptoms,
      arthritis, mononeuritis multiplex, and other manifestations that are also seen in
      various vasculitides. The rarity of abnormal angiogram findings and the high
      frequency of pANCA are characteristic of MPA. In most cases, the outcome is
      comparable with those of other systemic vasculitides, but relapses are frequent.

PMID- 10088764
TI  - Filtration leukocytapheresis therapy in rheumatoid arthritis: a randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine the efficacy and safety of filtration leukocytapheresis
      (LCP) for the treatment of rheumatoid arthritis (RA). METHODS: Twenty-five
      patients with drug-resistant RA were randomly assigned to undergo filtration LCP
      and 7 to undergo sham apheresis (control group) in a randomized, double-blind,
      placebo-controlled study. Three apheresis procedures were performed, with 1-week
      intervals between procedures. The efficacy of filtration LCP was evaluated
      according to the American College of Rheumatology definition of improvement in
      RA. Medications for each patient were unchanged for at least 6 months prior to
      enrollment and throughout the study. RESULTS: Tender joint counts, swollen joint
      counts, patient assessment of pain and global severity, physician assessment of
      global severity, and Health Assessment Questionnaire Disability Index were
      significantly improved in the LCP group compared with the control group (P < 0.05
      for patient assessment of pain; P < 0.01 for all others). Seventy-nine percent of
      the patients in the LCP group exhibited significant overall improvement, while
      none of the patients in the control group were improved (P < 0.001). CONCLUSION:
      The results indicate that filtration LCP is an effective and well-tolerated
      treatment for patients with drug-resistant RA.

PMID- 10088765
TI  - Tumor necrosis factor a microsatellite polymorphism is associated with rheumatoid
      arthritis severity through an interaction with the HLA-DRB1 shared epitope.
AB  - OBJECTIVE: To determine whether tumor necrosis factor microsatellite a (TNFa)
      polymorphism is associated with severity of rheumatoid arthritis (RA), and to
      examine the evidence for interaction between TNFa and the HLA-DRB1 shared epitope
      (SE). METHODS: One hundred seventy-one community-based white female RA patients
      were genotyped for both TNFa and HLA-DRB1 alleles. We performed pairwise
      association analyses, stratified analyses, and multivariate logistic regressions
      to determine whether TNFa was associated with 4 measures of RA severity, and
      whether there was significant interaction between TNFa and the HLA-DRB1 SE.
      RESULTS: Simple pairwise analyses did not reveal significant association between
      TNFa polymorphism and RA severity. However, when the data were stratified by the
      presence versus absence of the SE, striking associations were observed between
      TNFa allele 11 (TNFa11) and RA severity. These analyses also demonstrated
      significant interaction between TNFa11 and the SE (P = 0.07-0.005), and this was
      confirmed in our multivariate regressions. Specifically, the most severe outcomes
      were observed among individuals who had inherited both TNFa11 and the SE (61-71%
      had severe RA based on 1 of the 4 outcomes). In contrast, individuals who had
      inherited TNFa11 in the absence of the SE had the best outcomes (8-21% with
      severe RA). The odds ratios comparing these 2 groups ranged from 8.8 to 22.7 for
      the 4 severity measures. The differential effect of TNFa11 according to the
      presence versus absence of the SE (and vice versa) illustrated their interaction
      with respect to RA severity. CONCLUSION: The data suggest that TNFa is associated
      with RA severity through an interaction with the HLA-DRB1 SE.

PMID- 10088766
TI  - Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine serum lipoprotein(a) (Lp[a]) concentrations and to
      analyze the apolipoprotein(a) (Apo[a]) phenotype in patients with rheumatoid
      arthritis (RA). METHODS: The subjects included 131 patients with RA and 200
      healthy control subjects. Serum Lp(a) concentrations were measured by enzyme
      linked immunosorbent assay, and the Apo(a) phenotype was determined by
      immunoblotting. HLA-DR typing was also done. RESULTS: The mean serum Lp(a) level
      was significantly higher (P < 0.001) in the RA patients (27.5 mg/dl) than in the
      controls (15.0 mg/dl). The S3 allele was found in 70.0% of the patients versus
      39.5% of the controls (P < 0.001). There was no significant difference in HLA-DR4
      positivity between patients with and without the S3 phenotype. CONCLUSION: The
      serum Lp(a) level was increased in patients with RA, possibly partly because of
      S3 phenotype predominance.

PMID- 10088767
TI  - Detection of human retrovirus 5 in patients with arthritis and systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine whether human retrovirus 5 (HRV-5) infection is associated
      with autoimmune rheumatic disease. METHODS: DNA from patients with various
      disorders including inflammatory diseases and from normal subjects was tested by
      nested polymerase chain reaction (PCR) for HRV-5 proviral DNA. Positive results
      were confirmed by DNA sequencing. RESULTS: HRV-5 proviral DNA was detected in 53%
      of synovial samples from arthritic joints, in 12% of blood samples from patients
      with rheumatoid arthritis (RA), and in 16% of blood samples from patients with
      systemic lupus erythematosus. In contrast, it was not detectable by PCR of
      affected tissues from patients with several other autoimmune diseases and was
      found in only 1 of >200 tissue specimens obtained at autopsy from non-RA
      patients. Sequence analysis of the amplified viral segment showed genetic
      variation between samples with maintenance of the open reading frame, typical of
      a replicating infectious retrovirus. CONCLUSION: This is the first report of the
      frequent detection of HRV-5 in any disease. We propose that the possible
      involvement of HRV-5 in autoimmune and rheumatic disease should be investigated
      further.

PMID- 10088768
TI  - A critical evaluation of enzyme immunoassays for detection of antinuclear
      autoantibodies of defined specificities. I. Precision, sensitivity, and
      specificity.
AB  - OBJECTIVE: To determine the performance characteristics of enzyme-based
      immunoassay (EIA) kits for the detection of antinuclear and other autoantibodies
      of defined specificities. METHODS: Nine manufacturers of EIA kits to detect
      antibodies of defined specificities participated in a study in which they
      received coded sera from the Centers for Disease Control and Prevention. These
      coded sera contained different dilutions of antibody of one specificity mixed
      with sera containing antibodies of other specificities. The manufacturers were
      asked to use their standard technology to determine antibody content and send the
      data to a committee of the International Union of Immunological Societies for
      analysis. The data were analyzed for sensitivity and specificity in the detection
      of anti-double-stranded DNA (anti-dsDNA), anti-single-stranded DNA, antihistone,
      anti-Sm, anti-U1 RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 (DNA topoisomerase
      I), anticentromere, and anti-Jo-1 antibodies. In addition, replicate samples were
      included in the coded sera to evaluate the precision of each EIA method. RESULTS:
      Lack of sensitivity and specificity was most evident in the anti-dsDNA and anti
      Sm kits, although 2 kits for anti-dsDNA achieved acceptable sensitivity and
      specificity. Generally, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, anticentromere,
      and anti-Jo-1 kits performed well. Many false-positive results were obtained with
      a multiple myeloma serum containing cryoprecipitates, but multiple myeloma sera
      without cryoprecipitates presented no problem in the EIA system. Precision, based
      on evaluation of replicate samples, varied from very good to poor. CONCLUSION: No
      single manufacturer was clearly superior to others in terms of their products'
      overall sensitivity, specificity, and precision. Areas that needed improvement
      were in kits for the detection of antibodies to dsDNA and to Sm antigen. Some EIA
      kits achieved good sensitivity and specificity. Individual manufacturers were
      informed of the performance of their respective kits so they could take measures
      to correct perceived deficiencies and thus improve the reliability of a group of
      important diagnostic assays used in the evaluation of systemic rheumatic
      diseases.

PMID- 10088769
TI  - Influence of ethnic background on clinical and serologic features in patients
      with systemic sclerosis and anti-DNA topoisomerase I antibody.
AB  - OBJECTIVE: To investigate the effect of ethnicity on clinical and serologic
      expression in patients with systemic sclerosis (SSc) and anti-DNA topoisomerase I
      (anti-topo I) antibody. METHODS: Clinical and serologic features, as well as HLA
      class II allele frequencies, were compared among 47 North American white, 15
      North American black, 43 Japanese, and 12 Choctaw Native American SSc patients
      with anti-topo I antibody. RESULTS: The frequency of progressive pulmonary
      interstitial fibrosis was lower, and cumulative survival rates were better in
      white compared with black and Japanese patients. Sera of white and black patients
      frequently recognized the portion adjacent to the carboxyl terminus of topo I,
      sera of Japanese patients preferentially recognized the portion adjacent to the
      amino terminus of topo I, and sera of Choctaw patients recognized both portions
      of topo I. Anti-RNA polymerase II and anti-SSA/Ro antibodies were present
      together with anti-topo I antibody more frequently in sera of Japanese patients
      than in sera of white patients. The HLA-DRB1 alleles associated with anti-topo I
      antibody differed; i.e., DRB1*1101-*1104 in whites and blacks, DRB1*1502 in
      Japanese, and DRB1*1602 in Choctaws. Multivariate analysis showed that ethnic
      background was an independent determinant affecting development of severe lung
      disease as well as survival. CONCLUSION: Clinical and serologic features in SSc
      patients were strongly influenced by ethnic background. The variability of
      disease expression in the 4 ethnic groups suggests that multiple factors linked
      to ethnicity, including genetic and environmental factors, modulate clinical
      manifestations, disease course, and autoantibody status in SSc.

PMID- 10088770
TI  - Effects of joint lavage and steroid injection in patients with osteoarthritis of
      the knee: results of a multicenter, randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of joint lavage and intraarticular steroid
      injection, alone and in combination, in the treatment of patients with
      symptomatic knee osteoarthritis (OA). METHODS: Ninety-eight patients with painful
      tibiofemoral OA were enrolled in a prospective, randomized, controlled, 2 x 2
      factorial-design trial of 6 months' duration. The 4 treatment groups consisted of
      1) intraarticular placebo (1.5 ml of 0.9% normal saline), 2) intraarticular
      corticosteroids (3.75 mg of cortivazol in 1.5 ml), 3) joint lavage and
      intraarticular placebo, and 4) joint lavage and intraarticular corticosteroid.
      Outcome measures evaluated at baseline, week 1, week 4, week 12, and week 24
      included severity of pain (100-mm visual analog scale [VAS]), global status (100
      mm VAS), and Lequesne's functional index. RESULTS: No interaction between steroid
      injection and joint lavage was demonstrated. Patients who had undergone joint
      lavage had significantly improved pain VAS scores at week 24 (P = 0.020). In
      contrast, corticosteroid injection had no long-term effect (P = 0.313);
      corticosteroid injection was associated with a decrease in pain only at week 1 (P
      = 0.003) and week 4 (P = 0.020). After week 4, Lequesne's functional index was
      not significantly improved regardless of the assigned treatment. CONCLUSION:
      Compared with placebo, both treatments significantly relieved pain but did not
      improve functional impairment. The effects of the 2 treatments were additive.
      Cortivazol provided short-term relief of pain (up to week 4). The effects of
      joint lavage persisted up to week 24.

PMID- 10088771
TI  - The associations of bone mineral density and bone turnover markers with
      osteoarthritis of the hand and knee in pre- and perimenopausal women.
AB  - OBJECTIVE: To determine whether Caucasian women ages 28-48 years with newly
      defined osteoarthritis (OA) would have greater bone mineral density (BMD) and
      less bone turnover over time than would women without OA. METHODS: Data were
      derived from the longitudinal Michigan Bone Health Study. Period prevalence and 3
      year incidence of OA were based on radiographs of the dominant hand and both
      knees, scored with the Kellgren/Lawrence (K/L) scale. OA scores were related to
      BMD, which was measured by dual-energy x-ray absorptiometry, and to serum
      osteocalcin levels, which were measured by radioimmunoassay. RESULTS: The period
      prevalence of OA (K/L grade > or =2 in the knees or the dominant hand) was 15.3%
      (92 of 601), with 8.7% for the knees and 6.7% for the hand. The 3-year incidence
      of knee OA was 1.9% (9 of 482) and of hand OA was 3.3% (16 of 482). Women with
      incident knee OA had greater average BMD (z-scores 0.3-0.8 higher for the 3 BMD
      sites) than women without knee OA (P < 0.04 at the femoral neck). Women with
      incident knee OA had less change in their average BMD z-scores over the 3-year
      study period. Average BMD z-scores for women with prevalent knee OA were greater
      (0.4-0.7 higher) than for women without knee OA (P < 0.002 at all sites). There
      was no difference in average BMD z-scores or their change in women with and
      without hand OA. Average serum osteocalcin levels were lower in incident cases of
      hand OA (>60%; P = 0.02) or knee OA (20%; P not significant). The average change
      in absolute serum osteocalcin levels was not as great in women with incident hand
      OA or knee OA as in women without OA (P < 0.02 and P < 0.05, respectively).
      CONCLUSION: Women with radiographically defined knee OA have greater BMD than do
      women without knee OA and are less likely to lose that higher level of BMD. There
      was less bone turnover among women with hand OA and/or knee OA. These findings
      suggest that bone-forming cells might show a differential response in OA of the
      hand and knee, and may suggest a different pathogenesis of hand OA and knee OA.

PMID- 10088772
TI  - Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID
      mouse model.
AB  - OBJECTIVE: To investigate the effects of retrovirus-based gene delivery of
      inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in
      the SCID mouse model of rheumatoid arthritis (RA). METHODS: The MFG vector was
      used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55,
      viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The
      effect on invasion of these cells into human articular cartilage and on
      perichondrocytic cartilage degradation was examined after 60 days of
      coimplantation into the SCID mouse. RESULTS: TNFalphaR p55 gene transfer showed
      only a limited effect on inhibition of RA synovial fibroblast invasiveness and
      cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into
      the coimplanted cartilage was strongly inhibited by both viral and murine IL-10.
      Perichondrocytic cartilage degradation was not affected by either form of IL-10.
      CONCLUSION: The data show that cytokines can be successfully inserted into the
      genome of human RA synovial fibroblasts using a retroviral vector delivery
      system, and that the SCID mouse model of human RA is a valuable tool for
      examining the effects of gene transfer. In addition, inhibition of more than one
      cytokine pathway may be required to inhibit both synovial- and chondrocyte
      mediated cartilage destruction in RA.

PMID- 10088773
TI  - Efficacy of sustained blood levels of interleukin-1 receptor antagonist in animal
      models of arthritis: comparison of efficacy in animal models with human clinical
      data.
AB  - OBJECTIVE: To determine the role of interleukin-1 receptor antagonist (IL-1Ra) in
      rat adjuvant arthritis and rat type II collagen-induced arthritis, and to compare
      the efficacy in rat models with that seen in human clinical trials of IL-1Ra.
      METHODS: Rats with developing adjuvant arthritis or established collagen-induced
      arthritis were treated with IL-1Ra by continuous infusion in order to determine
      and maintain efficacious blood levels of this IL-1 inhibitory protein in the rats
      for comparison with human clinical data. The effects of treatment in the rats
      were monitored by sequential caliper measurement of the ankle joints,
      determination of final paw weights, and histologic evaluation with particular
      emphasis on bone and cartilage lesions. The effects of IL-1Ra on joint swelling
      and radiographic bone damage in patients with rheumatoid arthritis (RA) in a 6
      month trial were compared with the findings in rats. RESULTS: Dramatic
      differences in the profile of IL-1Ra activity were seen between the 2 groups of
      rats. Modest antiinflammatory effects were observed in the adjuvant arthritis
      rats treated with IL-1Ra. However, marked inhibition of bone resorption occurred,
      even at doses with which antiinflammatory activity was not seen. In contrast, IL
      1Ra treatment of rats with established collagen-induced arthritis resulted in
      nearly complete suppression of all aspects of the disease when adequate blood
      levels of IL-1Ra were maintained. Treatment of RA patients with IL-1Ra (150 mg
      daily) resulted in modest inhibition of joint swelling and inhibition of
      radiographic progression of bone lesions. CONCLUSION: IL-1 appears to be of major
      importance in mediating the bone resorption that occurs in rat adjuvant
      arthritis, but is less important in the pathogenesis of periarticular
      inflammation in this disease. In contrast, IL-1 is of major importance in
      mediating all aspects of disease progression in rat collagen-induced arthritis.
      Similar to the response in adjuvant arthritic rats, RA patients treated with IL
      1Ra showed only modest antiinflammatory activity, but had evidence of inhibition
      of progression of bone resorption. However, a comparison of the plasma levels of
      IL-1Ra in humans and rats suggests that the optimal level of dosing for
      continuous saturation of IL-1 receptors may not have been achieved in humans,
      although this was achieved in the rat studies.

PMID- 10088774
TI  - Synovial fluid transforming growth factor beta inhibits dendritic cell-T
      lymphocyte interactions in patients with chronic arthritis.
AB  - OBJECTIVE: To examine whether rheumatoid synovial fluid (SF) inhibits dendritic
      cell (DC) expression of the CD80 and CD86 costimulator molecules and contributes
      to SF T lymphocyte hyporesponsiveness. METHODS: Cell-free rheumatoid SF was
      tested for its effect on DC-stimulated autologous/allogeneic mixed lymphocyte
      reactions and for its effect on DC surface antigen expression, as assessed by
      flow cytometry. Blocking monoclonal antibodies were used to identify the SF
      cytokines that inhibited DC-T lymphocyte interactions. RESULTS: Low
      concentrations of SF (2.5%) could inhibit DC-mediated autologous and allogeneic T
      lymphocyte proliferation. This inhibitory effect could be reversed by
      neutralizing transforming growth factor beta (TGFbeta) and interleukin-2 (IL-2),
      but not by IL-12, in the SF. Hyaluronic acid, IL-6, IL-10, and tumor necrosis
      factor alpha were not associated with SF inhibition. In vitro culture alone and
      crosslinking with the CD40 ligand up-regulated DC CD80/CD86 expression and
      costimulator function, and this was not affected by inclusion of SF. In the
      presence of SF, DC clustered with autologous T lymphocytes showed decreased CD80
      and CD86 expression, and variable CD80/CD86 decreases were observed on DC
      clustered with allogeneic T lymphocytes. CONCLUSIONS: TGFbeta in SF appears to
      suppress T lymphocyte function, which may affect both signaling to DC and the
      induction of DC costimulator function.

PMID- 10088775
TI  - Tumor necrosis factor alpha regulation of the FAS-mediated apoptosis-signaling
      pathway in synovial cells.
AB  - OBJECTIVE: Fas-mediated apoptosis is observed in synoviocytes of patients with
      rheumatoid arthritis (RA), but not in those of patients with osteoarthritis (OA).
      The present study was conducted to elucidate the mechanisms that initiate
      induction of Fas-mediated apoptosis in RA synoviocytes. METHODS: Cultured OA
      synoviocytes, which are insensitive to Fas-mediated apoptosis in spite of Fas
      antigen expression, were used in these experiments. Synovial cell proliferation
      and cytotoxicity studies were performed using MTS and lactate dehydrogenase
      release assays. Surface expression of Fas antigen was analyzed by flow cytometry.
      The expression and function of apoptosis-signaling molecules, such as caspase 8
      and caspase 3, were examined by immunoblot analysis. RESULTS: Tumor necrosis
      factor alpha (TNFalpha) induced proliferation of cultured OA synoviocytes. Fas
      ligation with anti-Fas monoclonal antibody (mAb) resulted in cytotoxic activity
      against cultured OA synoviocytes that had been pretreated with TNFalpha for 5
      days, but not those pretreated for 2 days. In contrast, anti-Fas mAb did not show
      a cytotoxic effect against untreated cultured OA synoviocytes. A gradual up
      regulation of caspase 8 and caspase 3, which played a role in the caspase cascade
      for Fas-mediated apoptosis, was observed in TNFalpha-treated cultured OA
      synoviocytes. In addition, Fas ligation to TNFalpha-treated cultured OA
      synoviocytes induced activation of caspase 8 and caspase 3, with subsequent
      cleavage of poly(ADP-ribose) polymerase (PARP), a substrate of activated caspase
      3. More importantly, Z-IETD-FMK, a caspase 8 inhibitor, and Ac-DEVD-CHO, a
      caspase 3 inhibitor, almost completely inhibited Fas-mediated apoptosis of
      TNFalpha-treated cultured OA synoviocytes, whereas Ac-YVAD-CHO, a caspase 1
      inhibitor, did not. CONCLUSION: Our results clearly demonstrate that TNFalpha
      stimulates synovial cells to proliferate as well as sensitizes the cells for Fas
      mediated apoptosis, at least in part by up-regulation and activation of caspase 8
      and caspase 3. These findings suggest that TNFalpha may be one of the factors
      providing sensitization of synovial cells to Fas-mediated apoptosis in RA.

PMID- 10088776
TI  - Immune responses to cartilage link protein and the G1 domain of proteoglycan
      aggrecan in patients with osteoarthritis.
AB  - OBJECTIVE: To determine whether patients with osteoarthritis (OA) express
      cellular immunity to cartilage link protein (LP) and the G1 globular domain of
      proteoglycan (PG) aggrecan, and whether immunity to the G1 domain is influenced
      by the removal of keratan sulfate (KS). METHODS: LP and the G1 globular domain of
      PG were isolated from human and/or bovine cartilage and used in proliferation
      assays with peripheral blood lymphocytes (PBL) from 42 patients with OA and 40
      healthy control subjects. RESULTS: Patients with OA expressed a higher prevalence
      of cellular immunity to human cartilage LP (42.4%) compared with the control
      group (13.3%). The prevalence of immune reactivity to bovine LP in patients with
      OA was lower (35.7%) compared with the immunity to human LP, but remained similar
      in the control group (13.8%). PBL from patients with OA exhibited low reactivity
      to the native G1 domain of bovine PG. However, removal of KS chains from the G1
      globular domain resulted in increased cellular immune responses to the G1 domain
      in OA patients (45.8%) compared with the control group (7.7%). CONCLUSION: These
      results indicate the presence of immunity to cartilage-derived LP and the G1
      globular domain of PG aggrecan in patients with OA and the inhibitory effect of
      KS chains on the G1 domain on the expression of this immunity in OA patients.
      This immune reactivity is commonly observed in patients with inflammatory joint
      disease and can experimentally induce arthritis. Thus, it may be involved in the
      pathogenesis of OA.

PMID- 10088777
TI  - Changes in joint cartilage aggrecan after knee injury and in osteoarthritis.
AB  - OBJECTIVE: To determine the concentrations of aggrecan fragments in synovial
      fluid from patients with knee joint injury, osteoarthritis (OA), or acute
      pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity
      with the 846 epitope, a putative marker of cartilage aggrecan synthesis. METHODS:
      Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were
      obtained in a cross-sectional study. Study groups were acute PPA/ pseudogout (n =
      60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n =
      129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by
      competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by
      enzyme-linked immunosorbent assay using a monoclonal antibody (1-F21). Cartilage
      oligomeric matrix protein (COMP), C-propeptide of type II collagen (CPII), bone
      sialoprotein, matrix metalloproteinases 1 and 3, and tissue inhibitor of
      metalloproteinases 1 were previously quantified by immunoassays. RESULTS:
      Reactivity of the 846 epitope was increased in all study groups compared with the
      reference group, and was highest in patients with primary OA. The median levels
      (in microg fetal aggrecan equivalents/ml) of the epitope were 0.28 (range 0.24
      0.47) in the reference group, 0.48 (range 0.26-1.32) in PPA/pseudogout, 0.61
      (range 0.12-2.87) in ACL rupture, 0.53 (range 0.22-3.02) in meniscus lesion, and
      0.68 (range 0.31-4.31) in primary OA. The 846 epitope reactivity per microg
      aggrecan fragments in the joint fluid was higher in late-stage OA than in early
      stage OA. Epitope 846 reactivity correlated positively with several markers of
      matrix turnover, particularly with COMP (r(s) = 0.421) and CPII (r(s) = 0.307).
      CONCLUSION: The observed differences in 846 epitope reactivity in synovial fluid,
      and its concentration in relation to aggrecan and other markers of matrix
      turnover, were consistent with marked ongoing changes in aggrecan turnover after
      joint injury and in the development of OA. OA is thus a disease characterized by
      dynamic changes in tissue macromolecule turnover, which is reflected by
      measurable changes in aggrecan epitopes in the synovial fluid.

PMID- 10088778
TI  - Diacerhein treatment reduces the severity of osteoarthritis in the canine
      cruciate-deficiency model of osteoarthritis.
AB  - OBJECTIVE: To determine if diacerhein protects against the early stages of joint
      damage in a canine model of osteoarthritis (OA). METHODS: OA was induced in 20
      adult mongrel dogs by transection of the anterior cruciate ligament of the left
      knee. Beginning the day after surgery, dogs in the active treatment group were
      dosed twice a day with capsules of diacerhein, providing a total daily dose of 40
      mg/kg, for 32 weeks. Dogs in the control group received placebo capsules on the
      same schedule. Pathology in the unstable knee was assessed arthroscopically 16
      weeks after surgery and by direct observation when the dogs were killed 32 weeks
      after surgery. The severity of gross joint pathology was recorded, and samples of
      the medial femoral condyle cartilage and the synovial tissue adjacent to the
      central portion of the medial meniscus were collected for histologic evaluation.
      Water content and uronic acid concentration of the articular cartilage from the
      femoral condyle were determined, and collagenolytic activity in extracts of
      cartilage pooled from the medial and lateral tibial plateaus was assayed against
      14C-labeled collagen fibers. RESULTS: Diacerhein treatment slowed the progression
      of OA, as measured by grading of gross changes in the unstable knee at
      arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the
      time the animals were killed, 32 weeks after surgery (P = 0.05). However, 32
      weeks after ACL transection, the mean proteoglycan concentration and water
      content of the OA cartilage and the level of collagenolytic activity in extracts
      of the cartilage were not significantly different in the diacerhein treatment
      group than in the placebo treatment group. CONCLUSION: Diacerhein treatment
      significantly reduced the severity of morphologic changes of OA compared with
      placebo. These findings support the view that diacerhein may be a disease
      modifying drug for OA.

PMID- 10088779
TI  - Transduction mechanisms of porcine chondrocyte inorganic pyrophosphate
      elaboration.
AB  - OBJECTIVE: To investigate cellular signaling mechanisms that influence
      chondrocyte production of inorganic pyrophosphate (PPi), which promotes calcium
      pyrophosphate dihydrate (CPPD) crystal deposition. METHODS: Articular chondrocyte
      and cartilage cultures were stimulated with protein kinase C (PKC) activator and
      adenyl cyclase activator. Generation of extracellular PPi was measured. RESULTS:
      Adenyl cyclase activation resulted in diminished pyrophosphate generation. PKC
      activation stimulated pyrophosphate elaboration. CONCLUSION: Two signaling
      pathways, cAMP and PKC, modulate generation of extracellular pyrophosphate by
      cartilage and chondrocytes. They are novel targets for potentially diminishing
      extracellular pyrophosphate elaboration that leads to CPPD crystal deposition.

PMID- 10088780
TI  - Vasculitis in the Palmerston North mouse model of lupus: phenotype and cytokine
      production profile of infiltrating cells.
AB  - OBJECTIVE: To define the phenotype of cells in the perivascular and vascular
      infiltrates of Palmerston North (PN) mice and the cytokines that those cells
      produce. METHODS: Immunohistologic analysis, flow cytometric analysis, and
      reverse transcriptase-polymerase chain reaction (RT-PCR) studies were performed
      on tissues and cells from female PN mice and age-matched and sex-matched DBA/2
      mice. RESULTS: With aging, PN mice developed a female-predominant, lupus-like
      disease, with a severe systemic mononuclear cell perivasculitis and vasculitis.
      The perivasculitis involved arteries and veins in kidney, liver, brain, and lung;
      the vasculitis predominantly involved veins and venules. The perivascular and
      vascular infiltrates in female PN mice were composed mainly of an unusual cell
      type that expressed phenotypic markers characteristic of both T cells (Thy1+,
      CD3+, CD4+, T cell receptor + [TCR+]) and B cells (B220+). In addition, the
      infiltrates contained a smaller number of conventional CD4+,B220- T cells and
      macrophages. Very few CD8+ T cells or surface Ig+ B cells were seen. Unlike the
      Thy1+,B220+ T cells present in MRL/lpr mice, most of which were CD4-,CD8- and
      TCRalpha/beta+, the majority of the Thy1+,B220+ T cells in the
      perivascular/vascular infiltrates of PN mice were CD4+ and expressed either
      TCRalpha/beta or TCRgamma/delta. By immunohistologic staining, the cells in the
      perivascular and vascular infiltrates in the kidneys of older PN mice were shown
      to produce interleukin-4 (IL-4), IL-6, and IL-10, but not IL-2, interferon-gamma,
      transforming growth factor beta, tumor necrosis factor alpha, or IL-1beta. By RT
      PCR, the kidneys of older PN mice were found to express high levels of IL-4, IL
      6, and IL-10 messenger RNA. CONCLUSION: The vascular and perivascular infiltrates
      in PN mice are composed predominantly of an unusual subpopulation of T cells that
      are Thy1+,B220+,CD4+,CD8-, express either TCRalpha/beta or TCRgamma/delta, and
      produce mainly type 2 cytokines. The exact role of these cells in the
      immunopathogenesis of lupus-like disease in PN mice remains to be elucidated.

PMID- 10088781
TI  - Interferon-beta1A-induced polyarthritis in a patient with the HLA-DRB1*0404
      allele.
AB  - Human interferon-alpha (IFNalpha) and IFNbeta are administered for treatment of
      several diseases, including viral infections, malignancies, and multiple
      sclerosis (MS). IFNalpha therapy has been associated with the production of
      autoantibodies and the development of a variety of autoimmune disorders,
      including polyarthritis. This report describes the development of seronegative,
      symmetric polyarthritis in a patient with relapsing-remitting MS, after 8 weeks
      of therapy with IFNbeta1a. HLA phenotyping analysis of the patient revealed the
      presence of HLA-DRB1*0404, an allele known to be associated with the development
      of rheumatoid arthritis. Therefore, IFNbeta1a may have induced arthritis in a
      patient who was genetically predisposed to develop arthritis on the basis of HLA
      determinants. The English-language literature regarding IFNalpha- and IFNbeta
      induced polyarthritis is reviewed, and possible mechanisms for IFNalpha- and
      IFNbeta-induced autoimmunity, including the contribution of HLA determinants and
      nitric oxide overproduction, are discussed.

PMID- 10088782
TI  - Watermelon stomach.

PMID- 10088783
TI  - Sacroiliitis, hyperostosis sternoclavicularis, and psoriasis palmoplantaris in
      monozygotic twins.

PMID- 10088784
TI  - Spinal epidural hematoma complicating active systemic lupus erythematosus.

PMID- 10088785
TI  - Diffuse infiltrative lymphocytosis syndrome in a patient with anti-52-kd Ro/SSA
      and human immunodeficiency virus type 1.

PMID- 10088786
TI  - Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis.

PMID- 10088787
TI  - Lack of endothelial cell apoptosis in the dermis of tight skin 1 and tight skin 2
      mice.

PMID- 10088788
TI  - We need simple guidelines for reporting rates of rheumatic diseases.

PMID- 10088789
TI  - Significantly increased frequency of baseline IgA anti-type II collagen
      positivity in the placebo group in a study of oral type II collagen treatment of
      rheumatoid arthritis: comment on the article by Barnett et al.

PMID- 10088790
TI  - The influence of sex on the frequency of erosive disease and extraarticular
      manifestations in rheumatoid arthritis: comment on the article by Weyand et al.

PMID- 10088791
TI  - Sex-associated factors and the presentation of rheumatoid arthritis: comment on
      the article by Weyand et al.

PMID- 10088792
TI  - Expression of matrix metalloproteinase 1 in rodents: comment on the article by
      Huebner et al.

PMID- 10088793
TI  - Interleukin-10 promoter polymorphism and lupus nephritis: comment on the article
      by Mok et al.

PMID- 10088794
TI  - The role of carrier protein in the sensitivity of enzyme-linked immunosorbent
      assay for antiribosomal P protein antibodies: further comment on the article by
      Yoshio et al.

PMID- 10088795
TI  - Pyrophosphate arthritis after intraarticular injection of hyaluronan: comment on
      the article by Luzar and Altawil.

PMID- 10088796
TI  - A new scoring system for the detailed description of the distribution and
      thrombotic burden in deep leg vein thrombosis.
AB  - The scoring system most commonly used to date to describe the thrombotic burden
      of deep vein thrombosis (DVT) excludes several deep vein segments and is thereby
      of limited use in research. The aim of this prospective, comparative study was to
      develop a new scoring and distribution system that would include all major deep
      veins of the leg and pelvis. In total, 247 consecutive patients were included, of
      whom 105 had a positive phlebography. The positive phlebographies were registered
      in the new system and the result was compared with that obtained by the Marder
      system. In 72% (76/105) of the patients the DVT distribution was not completely
      described and the thrombotic burden was significantly underestimated by the
      Marder system. Of these, 12% (13/105) were not scored at all, thus representing
      false-negative investigations. It was possible to score all DVTs and important
      vein segments of these patients with the new system. The scoring system
      previously used excludes several deep vein segments. A description of the
      important vein segments, where DVT is shown to originate and propagate, is
      mandatory in a scoring system designed for the purpose of research of DVT and
      later detected deep vein insufficiency. The new system meets this demand.

PMID- 10088797
TI  - A universally applicable clinical classification of lymphedema.
AB  - A simple classification of lymphedema is presented that is based solely on
      clinical observation. It is suggested that the universal use of such a
      classification would facilitate the collection of meaningful epidemiologic data
      and would make possible understandable comparisons of the effectiveness of
      various treatment modalities.

PMID- 10088798
TI  - Randomized reliability study evaluating constant-load and graded-exercise
      treadmill test for intermittent claudication.
AB  - The aim of this randomized study was to compare the reliability of the treadmill
      test at constant-load (C-test, 3 km/hr; fixed grade of 12%) recommended in
      Germany with that of the graded-exercise test (G-test, 3 km/hr; increase in grade
      of 3.5% every 3 minutes) propagated in the United States. In 50 patients with an
      absolute claudication distance (ACD) in the C-test of between 50 and 400 m, the
      two treadmill tests were carried out in randomized order on one and the same day,
      and repeated on 3 days within 1 week. For the initial claudication distance
      (ICD), the intraclass correlation was 0.88 in the C-test and 0.87 in the G-test.
      For the ACD the coefficients were identical at 0.91. The within-subject variation
      (CVwithin) in the C-test and G-test was 25% and 27% for the ICD and for the ACD
      24% and 21%, respectively. The between-subject variation was very similar with
      72% and 73% (ICD) and with 78% and 68% (ACD). However, in ACDs below 100 m and
      between 100 to 150 m, the C-test showed significantly smaller coefficients of
      variation than the G-test: 13% vs 81% and 14% vs 50%, respectively. In
      conclusion, the results showed that both C-test and G-test are equally well
      reproducible.

PMID- 10088800
TI  - QT dispersion and early arrhythmic risk during acute myocardial infarction.
AB  - It has been suggested that QT dispersion (maximal minus minimal QT interval
      calculated on a standard 12-lead electrocardiogram) could reflect regional
      variations of ventricular repolarization and could provide a substrate for
      reentry ventricular arrhythmias. The present study evaluates QT dispersion in
      patients with acute myocardial infarction, assessing its relation with early
      severe ventricular arrhythmias and some clinical features. Three hundred three
      patients with acute myocardial infarction and a control group of 297 healthy
      subjects were studied. QT and QTc dispersion were determined on the
      electrocardiogram taken after 12 hours and on days 3 and 10 after symptoms onset
      and on the electrocardiogram taken in the control group. The average values of QT
      and QTc dispersions (ms) were as follows: 70.5 +/- 42.5-87 +/- 45.6 (12th hour),
      66.7 +/- 37.6-76.8 +/- 43.6 (day 3), 68.8 +/- 42.7-76.8 +/- 42.8 (day 10), versus
      43 +/- 13.2-53.9 +/- 16.2 (control group). There were statistically significant
      differences between QT and QTc dispersion recorded in normal subjects and in each
      of the three electrocardiograms taken in patients with infarction. A greater QT
      dispersion was recorded in patients with anterior infarction (78.9 +/- 38.5 vs
      64.9 +/- 42.8 in inferior/lateral infarction). In the first 3 days QT dispersion
      was not different in patients treated and untreated with thrombolysis, whereas on
      day 10 it was greater in untreated patients (74.9 +/- 45.3 vs 60.5 +/- 37.2).
      Creatine kinase peak level did not influence QT dispersion. In the first 72 hours
      of infarction, 37 patients developed ventricular fibrillation or sustained
      ventricular tachycardia. Higher early values of QT and QTc dispersion were found
      in patients who developed severe ventricular arrhythmias (107.8 +/- 62 and 124.8
      +/- 67.5 ms) than in patients without serious arrhythmias (62.9 +/- 32.2 and 80.1
      +/- 37.9 ms). These data suggest that: (1) QT dispersion increased during acute
      myocardial infarction. (2) The values were higher in the early hours and fell
      late after infarction with thrombolysis. (3) Greater QT dispersion is associated
      with severe ventricular arrhythmias.

PMID- 10088799
TI  - Smoking is associated with dose-related increase of intima-media thickness and
      endothelial dysfunction.
AB  - Cigarette smoking is firmly established as a risk factor for atherosclerosis.
      However, the exact mechanism causing smoking-related damage to the arterial wall
      and its relation to the atherosclerotic process is not known. Also unknown is the
      time delay between the start of smoking and the sequence of functional and
      morphologic changes occurring in the arterial wall caused by smoking and their
      interrelationship. Therefore, the aim of this study was to evaluate the acute and
      chronic effects of smoking on endothelium-dependent (flow-mediated) dilation
      (FMD) of the peripheral arteries, the effects of dose and duration of chronic
      smoking on intima-media thickness (IMT) of the carotid arteries, and their
      interrelationship. The study encompassed two groups of smokers. In group A there
      were 40 subjects of both sexes, who smoked on average 17.6 +/- 6.5 cigarettes per
      day, for 5 to 15 years (mean 8.95 +/- 4.0 years), mean age 28.1 years. Group B
      consisted of 42 smokers of both sexes who smoked 21.15 +/- 8.2 cigarettes/day for
      more than 15 years (mean 21.15 +/- 3.4 years), mean age 39.5 years. The control
      group consisted of 40 healthy subjects without major risk factors of
      atherosclerosis, mean age 29.1 years. By means of high-resolution ultrasound the
      brachial artery diameter was measured at rest and during reactive hyperemia
      (after release of a forearm tourniquet) and the flow-mediated, endothelium
      dependent dilation was calculated. The IMT of the carotid arteries was determined
      in all subjects by use of B-mode ultrasonography. Resting blood flow in the
      brachial arteries was significantly less in the smokers' groups than in controls
      (78.8 +/- 31.9 vs 134.9 +/- 45.0 mL/min, p<0.0001). This decrease was much more
      evident in female than in male smokers. Female smokers also had significantly
      smaller brachial artery diameter at rest. In smokers the FMD of the brachial
      artery was reduced (11 +/- 4% vs 7 +/- 4%, p<0.004) and the mean IMT was
      significantly greater than in controls (0.68 +/- 0.13 vs 0.59 +/- 0.04 mm,
      p<0.001). Impairments of FMD and IMT increase were related to the duration and to
      the number of cigarettes smoked. In all subjects IMT was significantly correlated
      with total and LDL cholesterol, fibrinogen, lipoprotein(a) concentration, body
      mass index, and age of the subjects, but multivariate analysis showed that only
      total dose smoked and fibrinogen concentration were independently related to IMT.
      The results of this study show that smoking is associated with dose-related
      impairment of FMD and increased IMT of the carotid arteries. Impairment of FMD
      occurs in smokers very early and is the earliest detectable event, preceding
      morphologic changes of the vessel wall. Some harmful effects of smoking on the
      vessel wall are gender related.

PMID- 10088801
TI  - ST-T alternans and myocardial ischemia.
AB  - Previous studies using intracoronary electrocardiography have demonstrated that
      ST-T alternans can develop during standard balloon coronary angioplasty. Total
      occlusion with a large amount of myocardium in jeopardy is the postulated
      prerequisite. In this study, the authors used perfusion balloons instead of
      standard balloons, so coronary perfusion was maintained and ischemia was
      minimized. Fourteen patients with standard balloon technique and 11 patients with
      perfusion balloon technique were studied. The ST segment was less elevated during
      perfusion angioplasty (0.15 +/- 0.05 mV vs 1.04 +/- 0.19 mV, p<0.001). There were
      six (43%) patients with ST-T alternans with standard balloon technique compared
      with none in the perfusion balloon group (p<0.001). In this study, the authors
      found that there was less ischemia, less ST segment elevation, and lack of ST-T
      alternans on the intracoronary electrocardiogram during perfusion balloon
      angioplasty. These findings support the postulate that a large amount of ischemic
      myocardium is a prerequisite for ST-T alternans.

PMID- 10088802
TI  - Clinical, echocardiographic, and angiographic profile of patients with double
      chambered right ventricle: experience with 48 cases.
AB  - Forty-eight patients with double-chambered right ventricle (DCRV) were
      prospectively studied over a 3-year period. Clinical, echocardiographic,
      hemodynamic, and angiographic studies were done in all. Three patients were
      studied postoperatively also. Fifteen patients underwent surgery confirming the
      diagnosis. Echocardiography detected anomalous muscle bundles (AMBs) in 39/41
      patients in whom this study was carried out. Angiographically AMBs were best
      demonstrated in anteroposterior views in a systolic frame. Common associated
      anomalies found with DCRV were ventricular septal defects (69%), pulmonary valve
      stenosis (38%), and double-outlet right ventricle (10%).

PMID- 10088803
TI  - Limb-threatening lower extremity ischemia successfully treated with intra
      arterial infusion--case reports.
AB  - The authors present two patients with acute arterial vasospasm of the lower
      extremities causing marked ischemia. One patient had a history of Raynaud's
      disease, the second had been taking Cafergot for migraine headaches. Both
      patients's were given a test dose of intra-arterial tolazoline (50 mg). The
      patient with Raynaud's disease demonstrated marked improvement diffusely and was
      successfully treated with overnight infusion of papaverine. The second patient,
      taking Cafergot, demonstrated no angiographic response to tolazoline. It was
      speculated that the arteries of this patient were thrombosed. The patient was
      successfully treated with urokinase and remained free of pain at the 15-month
      follow-up.

PMID- 10088804
TI  - Primary venous aneurysms--case reports.
AB  - Venous aneurysms are rare lesions that may be the source of pulmonary emboli and
      can result in death. The authors have recently treated several patients who had
      venous aneurysms of the upper extremity, lower extremity, and jugular system.
      Venous aneurysms usually appear to have a safe natural history in these
      locations, although all of the reported patients required surgery after the
      development of symptoms owing to complaints of pain, and/or cosmetic appearance,
      and/or a diagnosis of thrombosis. These cases are presented, along with a review
      of venous aneurysms occurring at other sites and their causes.

PMID- 10088805
TI  - Myocardial infarction in patients with systemic lupus erythematosus with normal
      findings from coronary arteriography and without coronary vasculitis--case
      reports.
AB  - The authors present the cases of two young patients, a man and a woman, who
      presented with myocardial infarction, in the absence of ischemic heart disease or
      stenosis of the coronary arteries. The woman was known to have systemic lupus
      erythematosus (SLE) for the past 3 years (the immunoglobulin M [IgM]
      anticardiolipins antibodies were positive), without a history of coronary risk
      factors. Suddenly she presented with acute chest pain on rest that lasted 4 hours
      and culminated in anterior wall myocardial infarction. She was admitted to the
      coronary care unit, where no thrombolysis was given. She did not have
      echocardiographic evidence of Libman-Sacks endocarditis, but myocardial
      infarction was evident at the electrocardiogram (ECG). The young man had SLE (the
      IgM anticardiolipins were absent, but he was positive for lupus anticoagulant
      antibodies), he was hyperlipidemic, was a moderate smoker and moderately obese,
      and had no history of ischemic heart disease. He suddenly presented with an acute
      myocardial infarction documented by ECG, enzymes, and gammagraphy. In both
      patients, coronary angiography findings were normal and myocardial biopsy did not
      show evidence of arteritis. The relevance of these cases is the rare association
      of ischemic heart disease in SLE, with normal coronary arteries and without
      evidence of arteritis or verrucous endocarditis.

PMID- 10088806
TI  - Successful percutaneous balloon mitral valvuloplasty in a patient with left
      atrial thrombus--a case report.
AB  - Percutaneous balloon mitral valvuloplasty (PBMV) described by Inoue et al, is a
      safe FDA (Food and Drug Administration) approved procedure in patients with
      severe mitral stenosis. One of the contraindications of the procedure is presence
      of a left atrial thrombus; however, it has been reported that intense warfarin
      therapy may led to dissolution of the thrombus. The authors report a patient who
      was referred for PBMV and was found to have a left atrial thrombus. After intense
      warfarin therapy, successful PBMV was undertaken without complications.

PMID- 10088807
TI  - Single coronary artery with "high take-off" origin in a patient with rheumatic
      mitral stenosis--a case report.
AB  - In this case report, a patient with rheumatic mitral stenosis and R-1 subtype
      single coronary artery arising from the ascending aorta ("high take-off" origin)
      and coursing between the aorta and pulmonary artery is presented. The clinical
      significance and differential diagnosis are discussed. To the authors' knowledge,
      this is the first case reported in the literature with a single R-1 subtype
      coronary artery that shows "high take-off" origin.

PMID- 10088808
TI  - Deposits and proteoglycan changes in primary and recurrent granular dystrophy of
      the cornea.
AB  - OBJECTIVE: To investigate the origin and distribution of granular deposits in the
      corneas of 3 patients with granular dystrophy, 1 of whom had previously received
      a lamellar keratoplasty in which the granular dystrophy had recurred. METHOD:
      Corneal tissue from 2 patients with primary granular dystrophy (patients 1 and 2)
      and from a patient with recurrent granular dystrophy (patient 3) was examined.
      Corneal graft tissue was fixed in (1) 3% glutaraldehyde in sodium cacodylate
      buffer, (2) 2.5.% glutaraldehyde in sodium acetate buffer containing cuprolinic
      blue, and (3) 4% paraformaldehyde in phosphate-buffered saline. RESULTS: In
      patient 1 (aged 48 years), electron-dense granular structures were observed in
      epithelium, Bowman layer, and throughout the stroma. Bowman layer was absent in
      several places. Patient 2 (aged 78 years) showed similar features except with
      more deposits in the stroma. In patient 3 (aged 48 years), granular structures
      were heavily deposited in the epithelium; there were also some deposits in the
      posterior (host) stroma, some of which were associated with partially degenerated
      keratocytes. Bowman layer appeared normal. In all 3 patients, the intracellular
      or extracellular granular structures were surrounded by fine fibrillar material
      and abnormal proteoglycans. Electron-lucent spaces within the corneal stroma
      contained large quantities of abnormal proteoglycan filaments that were attached
      in part to collagen fibrils. CONCLUSIONS: Results from patient 3 support an
      epithelial origin for the deposits, presumably from keratoepithelin, aggregated
      with other proteins. The role of keratocytes is less clear, although the presence
      of deposits in the stroma of all 3 patients, some associated with keratocytes,
      suggests that these cells might produce granular material in addition to abnormal
      proteoglycans.

PMID- 10088809
TI  - Iridolenticular contact decreases following laser iridotomy for pigment
      dispersion syndrome.
AB  - OBJECTIVE: To evaluate changes in anterior segment anatomy after laser iridotomy
      for pigment dispersion syndrome. METHODS: Ultrasound biomicroscopy was performed
      on 7 eyes of 7 untreated patients with reverse pupillary block and pigment
      dispersion syndrome. A radially oriented image with the probe perpendicular to
      the eye in the superior meridian was obtained before and at least 1 week after
      laser iridotomy in each eye. We assessed changes in angle recess area and iris
      lens contact distance. RESULTS: Mean +/- SD patient age was 31.3 +/- 5.7 years
      and mean +/- SD refractive error was -5.0 +/- 3.9 diopters. Angle recess area
      (mean +/- SD, 0.78 +/- 0.28 vs 0.35 +/- 0.11 mm2; P=.001, paired t test) and iris
      lens contact distance (2.05 +/- 0.28 vs 0.79 +/- 0.13 mm; P<.001) decreased
      following iridotomy. Central anterior chamber depth did not change. CONCLUSION:
      Flattening of the iris following laser iridotomy for pigment dispersion syndrome
      causes a decrease in iris-lens contact and angle width while lens position
      remains constant.

PMID- 10088810
TI  - Basal linear deposit and large drusen are specific for early age-related
      maculopathy.
AB  - OBJECTIVE: To determine the distributions of basal laminar and basal linear
      deposits in Bruch membrane (BM) with respect to age and early age-related
      maculopathy (ARM). METHODS: The foveas of 41 human eyes (<60 years [n = 9]; > or
      =60 years [n = 32]), preserved no later than 3.5 hours post mortem, were examined
      using light and electron microscopy. Ten eyes met histopathologic criteria of the
      Alabama Age-related Macular Degeneration Grading System for early ARM. We
      calculated the specificity, sensitivity, and odds ratios for the association of
      basal laminar and basal linear deposits with early ARM. RESULTS: Both deposits
      occurred only in eyes older than 60 years. The highest specificities and
      sensitivities for early ARM were attained for eyes that had basal linear deposits
      or large (>125 microm) drusen, followed by eyes with any quantity of basal
      laminar deposits that also contained membranous debris. Eyes with ARM were 24
      times more likely than age-matched control eyes to have basal linear deposits or
      large drusen (P = .002). CONCLUSIONS: Basal linear deposits and large drusen with
      membranous contents constitute different morphologic forms of the same ARM
      associated lesion and may be significant for progression to late ARM.

PMID- 10088811
TI  - The importance of qualitative vitreous examination in patients with acute
      posterior vitreous detachment.
AB  - OBJECTIVE: To determine whether patients with acute posterior vitreous detachment
      with pigmented vitreous granules or hemorrhage have a higher likelihood of
      retinal tear compared with those with qualitatively normal vitreous examination
      findings. METHODS: A multicenter cross-sectional study was performed in 3
      peripheral ophthalmic clinics. Patients with acute posterior vitreous detachment
      were examined for the presence or absence of vitreous pigment granules, vitreous
      hemorrhage, and horseshoe retinal tear. RESULTS: Fifty-nine consecutive patients
      with acute posterior vitreous detachment met our eligibility criteria. Eight
      patients had a retinal tear, and thus its prevalence in our study was almost 14%.
      Thirteen patients (22%) had a high likelihood because they had evidence of either
      pigmented vitreous granules or hemorrhage. The prevalence of retinal tear in the
      setting of acute posterior detachment associated with vitreous hemorrhage alone,
      pigment alone, or vitreous hemorrhage and pigment was 54%. Patients with
      posterior vitreous detachment with pigmented vitreous granules or hemorrhage were
      significantly more likely to have a retinal tear (odds ratio, 52.0; 95%
      confidence interval, 5.4-497.0). Patients with a retinal tear were 7 times more
      likely to have pigmented vitreous granules or hemorrhage (LR + ve = 7.4, in which
      LR + ve indicates positive likelihood ratio; 95% confidence interval, 3.3-16.4).
      CONCLUSION: Patients with posterior vitreous detachment with vitreous pigment
      granules or hemorrhage are 52 times more likely to have a retinal tear compared
      with those who have normal findings on qualitative vitreous examination.

PMID- 10088812
TI  - Tonic ocular tilt reaction simulating a superior oblique palsy: diagnostic
      confusion with the 3-step test.
AB  - BACKGROUND: The tonic ocular tilt reaction (OTR) consists of vertical divergence
      of the eyes (skew deviation), bilateral conjugate ocular torsion, and paradoxical
      head tilt. The head and superior pole of both eyes are rotated toward the
      hypotropic eye. OBJECTIVE: To describe ocular motility and torsion findings in 5
      patients with OTRs that mimicked superior oblique palsies (SOPs). RESULTS: In 5
      patients, results of the 3-step test suggested an SOP (bilateral in 1 patient);
      however, no patient had the expected excyclotorsion of the hypertropic eye. Two
      patients had conjugate ocular torsion (intorsion of the hypertropic eye and
      extorsion of the hypotropic eye), and 2 patients had only intorsion of the
      hypertropic eye. All had other neurologic features consistent with more
      widespread brainstem disease. CONCLUSIONS: Vertical ocular deviations that 3-step
      to an SOP are not always caused by fourth nerve weakness. When a patient with an
      apparent fourth nerve palsy has ocular torsion that is inconsistent with an SOP,
      OTR should be suspected, especially if vestibular system or posterior fossa
      dysfunction coexists. The rules for the 3-step test for an SOP may be fulfilled
      by damaging the otolithic projections corresponding to projections of the
      contralateral anterior semicircular canal. Because results of the Bielschowsky
      head tilt test may be positive in patients with the OTR, the feature
      distinguishing OTR from an SOP is the direction of torsion. We advocate use of a
      fourth step-evaluation of ocular torsion-in addition to the standard 3 steps.

PMID- 10088813
TI  - Baseball hardness as a risk factor for eye injuries.
AB  - BACKGROUND: Baseball is the leading cause of sports-related eye injuries in young
      persons. It is known that softer baseballs reduce the potential for brain and
      cardiac injury, but it has been speculated that softer baseballs may increase eye
      injuries by intruding more into the orbit. It also has been claimed that softer
      baseballs would change the "feel" of the game. OBJECTIVES: To determine the
      orbital intrusion and eye injury potential of baseballs of varying hardness, and
      whether a player can feel the difference between these different baseballs. MAIN
      OUTCOME MEASURES: Orbital force and penetration of baseballs of various hardness
      into an artificial orbit. Ability of subjects of varying age and baseball
      experience to determine the hardness of baseballs. RESULTS: The peak orbital
      force and force onset rate from softer baseballs, at all impact velocities, were
      less than the force and force onset rate from baseballs that had hardness equal
      to, or greater than, major league baseballs. The softest (10% of major league
      hardness) baseballs intruded into the orbit significantly more than balls that
      were 15% of major league hardness or harder. Children younger than 14 years could
      not differentiate balls 15% of major league hardness or harder, and adults could
      not differentiate 20% of major league hardness or harder from each other or from
      major league balls. CONCLUSION: The potential for injury to the unprotected eye
      from soft baseballs is significant, but not greater than that from a major league
      baseball. Baseballs that are 15% to 20% of major league ball hardness are
      recommended for youth baseball because these balls feel like major league balls,
      reduce the potential for brain injury and commotio cordis, cause less pain on
      impact, and do not increase the potential for eye injury to the unprotected
      player. Eye injuries in youth baseball could be minimized by the use of
      protective eyewear that conforms to the standard specifications of the American
      Society of Testing and Materials (Philadelphia, Pa), standards F910 (for batters
      and baserunners) and F803 (for fielders).

PMID- 10088814
TI  - Pharmacological validation of a feline model of steroid-induced ocular
      hypertension.
AB  - OBJECTIVE: To validate pharmacologically the feline model of steroid-induced
      ocular hypertension. METHODS: Serial studies were conducted in domesticated adult
      female cats trained to accept topical ocular drug administration and
      pneumotonometry. To establish intraocular pressure (IOP) values for each study,
      measurements were performed at the same time of day for 6 consecutive days.
      Beginning on day 7, cats received either steroid or vehicle administered
      topically to both eyes three times a day for approximately 28 days. The IOP
      measurements were performed daily. RESULTS: After 5 to 7 days of treatment with
      0.1% dexamethasone or 1.0% prednisolone acetate, IOP began to increase, reaching
      peak values within 2 weeks. These values were sustained throughout dosing but
      declined rapidly to baseline upon cessation of treatment. Maximum IOPs for the
      dexamethasone- and prednisolone-treated groups averaged 4.5 +/- 0.3 mm Hg (n =
      12) greater than the mean IOP value obtained in vehicle-treated cats. Cats
      treated with 0.25% fluorometholone, 1.0% loteprednol etabonate, and 1.0%
      rimexolone exhibited increases of 0.6, 1.2, and 1.7 mm Hg, respectively. These
      values were significantly lower than those observed following treatment with
      dexamethasone or prednisolone. CONCLUSIONS: The ocular hypertensive effects of
      selected anti-inflammatory topical ocular steroids in this model are consistent
      with clinical findings. CLINICAL RELEVANCE: This feline model is a useful tool
      for assessing the potential IOP liability of novel anti-inflammatory steroids.

PMID- 10088815
TI  - Antineoplastic effect and toxicity of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 in
      athymic mice with Y-79 human retinoblastoma tumors.
AB  - OBJECTIVES: To evaluate the in vivo efficacy and toxicity of the 1,25-dihydroxy
      16-ene-23-yne-vitamin D3 (16,23-D3) analogue in athymic nude mice injected with Y
      79 human retinoblastoma cells and to compare the efficacy and toxicity of this
      compound with those of 1,25-dihydroxycholecalciferol (D3, calcitriol). METHODS:
      Thirty athymic nude mice (4-6 weeks old) were injected subcutaneously with 1 x
      10(7) Y-79 human retinoblastoma cells suspended in a 1:1 mixture of Iscove
      culture medium supplemented with 20% fetal bovine serum and basement membrane
      matrix suspension. Five days after tumor injection, the mice were randomized to 3
      groups of 10 mice each. The first group served as a control group and received
      intraperitoneal injections of 0.25 mL of mineral oil (vehicle) 5 times a week.
      The second group received intraperitoneal injections of 0.05 microg of calcitriol
      in 0.25 mL of mineral oil intraperitoneally 5 times a week. The third group
      received intraperitoneal injections of 0.5 microg of 16,23-D3 in 0.25 mL of
      mineral oil 5 times a week. Injections were continued for 5 weeks, during which
      tumor size and mouse weight were individually measured. Toxicity was assessed by
      clinical measures such as lethargy, weight loss, and death. The mice were then
      killed and the size, volume, and weight of each tumor were determined. Also, in
      representative animals in each group, kidneys were evaluated for calcification
      and serum calcium concentration was measured. RESULTS: All experimental and
      control animals developed tumors subcutaneously. The 16,23-D3-treated mice had
      significantly smaller average tumor size (1.55 cm3) than the control mice (3.45
      cm3) (P = .02), less gain in average body weight from the beginning of treatment
      (2.4 g vs 5.5 g) (P= .06), and a 40% mortality. The calcitriol-treated mice did
      not have significantly smaller average tumor size (1.26 cm3) than the 16,23-D3
      treated mice (P = .35), had significant body weight loss compared with the
      control animals (calcitriol-treated mice lost 4.03 g) (P =.001), and had a
      mortality of 90% by the completion of the experiment. Histologically, there was
      no difference in the degree of tumor necrosis and calcification between control
      and experimental mice. Serum calcium concentrations were equivalent between the
      control (2.15 mmol/L [8.6 mg/dL]) and experimental groups (calcitriol, 1.88
      mmol/L [7.5 mg/dL] [P = .97]; 16,23-D3, 2.15 mmol/L [8.6 mg/dL] [P = .42]). Mild
      bilateral renal tubular calcification occurred in 3 of 4 mice in the calcitriol
      treated group and in 2 of 4 mice in the 16,23-D3-treated group. CONCLUSIONS: The
      growth of subcutaneous Y-79 human retinoblastoma cells in athymic nude mice is
      significantly reduced by treatment with intraperitoneal injections of 16,23-D3.
      The antineoplastic effect of calcitriol is not statistically significantly
      different but is associated with significantly more toxicity. 1,25-Dihydroxy-16
      ene-23-yne-vitamin D3 may be a useful chemotherapeutic adjunct in the treatment
      of retinoblastoma.

PMID- 10088816
TI  - Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and
      correlation with germline mutation.
AB  - OBJECTIVES: To examine the epidemiologic and clinical characteristics of the
      ocular manifestations of von Hippel-Lindau (VHL) disease and to detect phenotype
      genotype relationships of disease severity. DESIGN: A cross-sectional clinical
      and molecular genetic study. PATIENTS AND METHODS: One hundred eighty-three
      affected VHL gene carriers from 81 unrelated pedigrees were interviewed and
      examined; clinical data were also obtained from 12 living and 39 deceased
      affected relatives. DNA extracted from venous blood was used to identify
      mutations in the VHL gene. RESULTS: The prevalence of ocular angiomatosis
      (hemangioblastomas) in von Hippel-Lindau disease was 67.8% (124/183), and the
      mean number of angiomas in gene carriers was 1.85 (range, 0-15). Neither
      prevalence nor angioma count increased with age. Severe vision loss in 1 or both
      eyes was associated with presentation at a young age. The cumulative probability
      of incurring vision loss by age 50 years was 35% in all gene carriers, 55% in
      those with angiomatosis, and significantly worse in those coming to us with
      symptoms. Angiomas were nonrandomly distributed in the fundus, occurring rarely
      at the posterior pole (1% of retinal tumors) and commonly on the optic disc (8%
      of eyes) and supratemporal retina. Complications of ocular angiomatosis included
      disc and retinal neovascularization; secondary angioma formation; retinal
      detachment, exudation, and membrane; and retinal and vitreous hemorrhage. Germ
      line VHL mutations were detected in 161 of 183 patients and 69 (85%) of 81
      pedigrees and included deletions (n= 16), missense (mutations causing amino acid
      substitutions; n = 24), nonsense (premature stop codons; n = 15), frameshift (n =
      13), and splice-site (n = 1) mutations. There was no association between the type
      or position of mutation and the severity of ocular angiomatosis. CONCLUSIONS: A
      systematic clinical description of a large cohort of VHL gene carriers further
      defines the ocular phenotype. There is no general influence of germline mutation
      on severity of ocular disease in VHL. CLINICAL RELEVANCE: The ophthalmic and
      molecular genetic description of patients with VHL disease.

PMID- 10088817
TI  - Racial difference in the incidence of retinal detachment in Singapore.
AB  - OBJECTIVE: To determine the incidence of retinal detachment (RD) operations in a
      multiracial Southeast Asian population. DESIGN: Population-based incidence study
      using a universal medical savings database in Singapore. METHODS: Information on
      all RD operations performed for rhegmatogenous RD (International Classification
      of Diseases, Ninth Revision, Clinical Modification code 361.0) between 1993 and
      1996 was retrieved and analyzed from a population-wide, government-administered
      medical savings database. Exudative, tractional, and unoperated-on rhegmatogenous
      RD are excluded. The 1990 Singapore population census was used to allow an
      estimation of age-, sex-, and race-specific annual incidence of RD. RESULTS:
      Between 1993 and 1996, 1126 RD operations were performed on Singapore residents.
      The average annual incidence of RD operations was 10.5 per 100,000 population
      (95% confidence interval [CI], 10.2-10.9). The annual incidence was highest for
      Chinese (age-adjusted incidence, 11.6 per 100,000), followed by Malays (7.0 per
      100,000), and lowest for Indians (3.9 per 100,000). The age-adjusted relative
      risk of RD operation for Chinese compared with Indians was 3.0 (95% CI, 2.9-3.1).
      Males were twice as likely as females to require RD surgery (age-adjusted
      relative risk, 2.0; 95% CI, 1.7-2.4). Chinese men 40 years and older had a 30.9
      times higher risk (95% CI, 9.9-96.1) than Indian females younger than 40 years.
      CONCLUSION: The incidence of RD is strongly associated with male sex and ethnic
      origin.

PMID- 10088818
TI  - Nonarteritic anterior ischemic optic neuropathy: enigma variations.

PMID- 10088819
TI  - Punctal occlusion.

PMID- 10088820
TI  - Oral acyclovir suppresses recurrent epithelial and stromal herpes simplex.

PMID- 10088821
TI  - Commentary on caring for the uninsured and underinsured.

PMID- 10088822
TI  - The fine structure of an iridectomy specimen from a patient with latanoprost
      induced eye color change.

PMID- 10088823
TI  - Pseudocapsulorrhexis in a patient with iridocorneal endothelial syndrome.
AB  - We describe a patient with Chandler's syndrome variant of the iridocorneal
      endothelial syndrome in whom ectopic Descemet's membrane was found
      intraoperatively on the anterior surface of the lens. Initially, the membrane was
      confused with the anterior lens capsule during extracapsular cataract extraction,
      leading to the performance of a pseudocapsulorrhexis. Electron microscopy
      disclosed that the epilenticular membrane was composed of multiple layers of
      abnormal basement membrane consistent with the iridocorneal endothelial syndrome.

PMID- 10088824
TI  - Photoreceptor rosettes in autosomal dominant retinitis pigmentosa with reduced
      penetrance.
AB  - We performed histopathologic and immunofluorescence studies of autopsy eyes from
      a 73-year-old woman with autosomal dominant retinitis pigmentosa from a family
      with reduced penetrance. Light microscopic examination showed extensive
      photoreceptor loss in most regions. In the temporal midperiphery of the retina,
      there were patches of remaining photoreceptors, some arranged in rosettes.
      Electron microscopic examination showed that these rosettes were composed mostly
      of rods, with a few cone-like inner segments. The malformed photoreceptor
      elements in the rosette lumens stained positively with anti-rhodopsin, but not
      with anti-red- and green-cone opsin or anti-blue-cone opsin. To our knowledge,
      this is the first report of photoreceptor rosettes containing rod photoreceptors
      in a case of retinitis pigmentosa. Future studies of additional patients will be
      needed to determine if the rod-abundant rosettes seen in our patient are a
      characteristic finding of autosomal dominant retinitis pigmentosa with reduced
      penetrance.

PMID- 10088825
TI  - Idiopathic juxtafoveolar retinal telangiectasis and pigment epithelial
      hyperplasia: an optical coherence tomographic study.

PMID- 10088826
TI  - Diffuse and circumscribed choroidal hemangiomas in a patient with Sturge-Weber
      syndrome.

PMID- 10088827
TI  - Surgically induced detachment of the anterior hyaloid membrane from the posterior
      lens capsule.
AB  - Vitreous hemorrhage adhering to the posterior lens capsule prevents adequate
      visualization of the vitreous cavity and fundus during vitreous surgery and
      during the dissection of fibrovascular membranes. This type of hemorrhage is
      difficult to remove by aspiration or resection using a vitreous cutter. We have
      developed a new technique designed to detach surgically the anterior vitreous for
      the removal of hemorrhage in patients with proliferative diabetic retinopathy. In
      this hydrodissection technique, the anterior vitreous is detached from the
      posterior lens capsule by a forced injection of infusion fluid into the anterior
      chamber. This technique separates the vitreous hemorrhage adhering to the
      posterior lens capsule and allows its removal.

PMID- 10088828
TI  - Retained intraocular metallic foreign body masquerading as a ciliary body
      melanoma with extrascleral extension.

PMID- 10088829
TI  - Canthaxanthine retinopathy.

PMID- 10088830
TI  - Orbital osteoid osteoma.

PMID- 10088831
TI  - Hyperopic automated lamellar keratoplasty.

PMID- 10088832
TI  - Hyperopic automated lamellar keratoplasty.

PMID- 10088833
TI  - Pressure or progression?

PMID- 10088834
TI  - Early and late acute respiratory distress syndrome: two distinct clinical
      entities.
AB  - BACKGROUND: Despite numerous advances in surgical critical care and ventilatory
      management, mortality rates for acute respiratory distress syndrome (ARDS) have
      remained relatively constant. Pressure-limited and non-pressure-limited
      ventilatory techniques have been advocated with disparate results. We
      hypothesized that there are two forms of ARDS, which may account for the
      conflicting clinical reports. METHODS: Patients with posttraumatic ARDS were
      identified and reviewed. ARDS was defined as PaO2/FiO2 ratio less than 200 with
      diffuse bilateral infiltrates on chest radiograph and no congestive heart
      failure. Patients were analyzed relative to injury mechanism, transfusions, fluid
      balance, presence of pneumonia (defined as > or =10(5) colony-forming units/mL in
      bronchoalveolar lavage effluent), and outcome. All were managed with a non
      pressure-limited strategy. RESULTS: During a 5.5-year period, 178 patients with
      posttraumatic ARDS were identified. Mean Injury Severity Score and age were 29
      and 40 years, respectively. Patients were stratified by time of ARDS diagnosis.
      Eighty-two patients (46%) had early ARDS (within 48 hours after admission), and
      96 patients (54%) had late ARDS (>48 hours between admission and diagnosis).
      There were no differences in Injury Severity Score, but the late group was
      significantly older. The early ARDS group was characterized by profound
      hemorrhagic shock and had significant differences from the late group in
      incidence of penetrating injury (30 vs. 10%; p<0.001), admission base deficit (
      7.7 vs. -4.2 mEq/L; p<0.001), 48-hour transfusions (19.7 vs. 9.4; p<0.0001),
      initial 5-day fluid balance (19.9 vs. 10.1 L; p<0.0001), and initial PaO2/FiO2
      (121 vs. 141; p<0.007). Pneumonia before ARDS was significantly associated with
      late ARDS (38 vs. 9%; p<0.001). ARDS-related mortality was primarily caused by
      hemorrhagic shock in the early group and progressive multiple organ failure in
      the late group. CONCLUSION: There are two distinct forms of posttraumatic ARDS.
      Early ARDS is characterized by hemorrhagic shock with capillary leak. Late ARDS
      frequently follows pneumonia and is associated with multiple system injury.
      Further studies should differentiate between these two distinct syndromes.

PMID- 10088835
TI  - Prospective randomized trial of thoracostomy removal algorithms.
AB  - INTRODUCTION: The preferred chest tube (CT) removal algorithm has not yet been
      established. The purpose of this study was to determine which technique, water
      seal or suction, allowed for shorter CT duration. In addition, the recurrent
      pneumothorax (PTX) rate, the need for CT reinsertion, and the total number of
      chest x-ray films (CXR) were determined. METHODS: Prospective randomized trial of
      205 trauma patients, older than 15 years of age, requiring tube thoracostomy for
      blunt and penetrating trauma. Patients requiring mechanical ventilation more than
      24 hours were excluded from the study. Informed consent was obtained from all
      patients. Chest tubes were randomized for removal when output was less than 150
      mL/24 hours, CXR revealed no significant PTX, and no air leak was present.
      Patients in the water seal group were disconnected from low wall suction and a
      CXR was obtained 6 to 8 hours later. Chest tubes in the no water seal group were
      disconnected from wall suction and pulled immediately. All tubes were removed by
      using standard protocol with patients at maximal inspiratory effort. A follow-up
      CXR was obtained after removal. RESULTS: Of the 205 patients, 93 patients (45 %)
      were randomized to the water seal group and 112 patients (54%) to the no water
      seal group. Four patients in the water seal group developed a PTX before CT
      removal and were considered treatment failures. After CT removal, repeat PTX was
      seen in 13 patients in the water seal group and in 9 patients in the no water
      seal group. However, seven patients in the no water seal group required CT
      reinsertion compared with one in the water seal group (p<0.05). Average number of
      CXR in the water seal group was 6.5 compared with 5.5 radiographs in the no water
      seal group. There was no difference in chest tube duration or hospital length of
      stay between groups for either all patients or only those patients with isolated
      chest injuries. Patients who required another CT had a hospital length of stay
      twice that of patients who did not. CONCLUSIONS: It is possible that patients in
      the no water seal group did not have sufficient time for a possible PTX to
      evolve, which resulted in a larger and more significant PTX requiring another CT.
      Although there was no difference in chest tube duration between the no water seal
      and water seal groups, a short trial of water seal appears to allow occult air
      leaks to become clinically apparent and reduces the need for another CT.

PMID- 10088836
TI  - Synergistic effect of hyperoxia and immunoglobulin A on mucosal barrier defense.
AB  - BACKGROUND: Hyperoxia has been reported to be protective against gut-derived
      sepsis. Although secretory immunoglobulin A (IgA) is primarily responsible for
      humoral defense of mucosal surfaces, a potential synergistic effect with
      hyperoxia is unknown. An asanguineous cell monolayer system was used to study
      these aspects in vitro. METHODS: MDCK cells were grown as polarized monolayers in
      a two-chamber culture system. Apical chambers were inoculated with 10(8)
      Escherichia coli M14 with or without polyclonal IgA and incubated in a 21 or 95%
      O2 environment. Basal medium was sampled at 90 and 180 minutes for bacterial
      translocation. In a second experiment, MDCK cells were lysed at 90 minutes and
      intracellular bacteria were quantitated. RESULTS: Bacterial translocation was
      decreased versus normoxia by the treatment groups IgA without hyperoxia or IgA
      with hyperoxia at 90 minutes. Bacterial internalization at 90 minutes was reduced
      to the greatest extent by the combined effects of hyperoxia and IgA.
      Translocation data at 180 minutes confirmed the additional protective effect of
      hyperoxia with IgA. CONCLUSION: Hyperoxia exerts a significant protective effect
      on barrier function independent of enhanced leukocyte function. Hyperoxia has an
      added effect to the mucosal defense provided by IgA.

PMID- 10088837
TI  - Computed tomographic angiography as a screening modality for blunt cervical
      arterial injuries: preliminary results.
AB  - BACKGROUND: The diagnosis of blunt cervical arterial injury (CAI) is made
      difficult by its infrequent occurrence and delayed presentation. Beginning in
      January of 1995, we used computed tomographic angiography (CTA) of the neck to
      screen for CAI. We hypothesized that CTA could be incorporated into the workup of
      patients sustaining blunt neck injury as a screening modality for CAI and that
      CTA would increase the early detection of CAI. METHODS: Retrospective review of
      all CAI for the years January of 1988 to June of 1997 at a Level I trauma center.
      CAI diagnosed before introduction of CTA (pre-CTA; January of 1988 to December of
      1994) were compared with those after (post-CTA; January of 1995 to June of 1997).
      RESULTS: The overall incidence of CAI for the entire time period was 0.11%. Motor
      vehicle crash (53%) was the most common mechanism, with focal neurologic deficit
      (23%) or seizures (17.6%) the most common presenting clinical symptoms. CTA added
      only a few additional minutes to the time required for the workup of patients
      sustaining blunt neck injury in whom CAI was suspected. The incidence of CAI
      increased from 0.06% pre-CTA to 0.19% post-CTA (p = 0.02; Fisher exact test). CTA
      was associated with a decrease in mean time to make the diagnosis of CAI (156
      hours pre-CTA vs. 5.9 hours post-CTA). In addition, CTA was associated with a
      decrease in the incidence of permanent neurologic sequelae from CAI (50% pre-CTA
      vs. 0% post-CTA; p = 0.07; Fisher exact test). CONCLUSION: We conclude that CTA
      does not significantly increase the time of the diagnostic workup of the patient
      with injuries caused by blunt trauma. The introduction of CTA at our institution
      was associated with an increase in the detection rate of CAI. Earlier detection
      of CAI may allow for more timely therapeutic intervention and potentially prevent
      permanent neurologic sequelae.

PMID- 10088838
TI  - Organ injuries associated with femoral fractures: implications for severity of
      injury in motor vehicle collisions.
AB  - OBJECTIVE: To determine if motor vehicle collisions (MVCs) resulting in femoral
      fractures were associated with a different injury severity and pattern of injury
      compared with crashes in which victims did not sustain femoral fractures.
      METHODS: Retrospective review of seriously injured motor vehicle occupants
      admitted to a regional trauma unit (Hamilton General Hospital) during a 69-month
      period (April 1991 to December 1996) for whom detailed crash details were known.
      RESULTS: Data for 733 motor vehicle occupants with Injury Severity Scores greater
      than 12 were available; 112 occupants (15.3%) sustained femoral fractures, and
      621 occupants (84.7%) did not sustain femoral fractures. Victims with femoral
      fractures had a significantly higher mean Injury Severity Score (29.4 compared
      with 25.3 for non-femoral fracture group; p<0.001). The femoral fracture group
      had a higher incidence of bowel (p<0.012) and hemopneumothorax (p<0.02) injuries
      as well as an increased incidence of upper and lower extremity (p<0.001) and
      pelvic (p<0.05) fractures. CONCLUSION: The presence of a femoral fracture is
      strongly associated with the pattern and severity of injuries sustained by
      occupants in MVCs. A high index of suspicion is warranted in identifying
      associated organ injuries in MVC victims with concomitant femoral fractures.

PMID- 10088839
TI  - Reamed intramedullary nailing of the femur: 551 cases.
AB  - BACKGROUND: The care of the patient with the fractured femur entails a multiple
      surgical team approach. Healing of the fracture and expediency in the operating
      room are both important. We sought to determine the results of the treatment of
      fractures of the femoral shaft with interlocking femoral nails inserted with
      closed techniques, and to compare the outcomes of fractures nailed by using a
      fracture table with those stabilized with the leg draped free on a radiolucent
      table. METHODS: Eight hundred eighty-two consecutive patients with fractures of
      the femoral shaft treated with a first-generation intramedullary nail at the
      authors' institution during the years 1986 to 1996 were identified. Five hundred
      fifty-one fractures in 515 patients met the inclusion criteria. RESULTS:
      Treatment with an intramedullary nail led to a union rate of 98.9%. There were
      six infections, all occurring in closed fractures. Thirty-eight percent of the
      fractures had hardware removed, most commonly because of pain. One nail and 13
      locking bolts broke. Four hundred eighteen fractures had adequate radiographs
      available to assess fracture alignment. No fracture healed with more than 10
      degrees of angulation in either plane. Forty-four fractures healed with more than
      5 degrees of angulation. A distal third fracture was found to be associated with
      an increased incidence of malalignment. There were no differences in outcomes
      between fractures stabilized with or without a fracture table. CONCLUSION: Reamed
      intramedullary nailing of femoral shaft fractures results in a low rate of
      nonunion, malunion, infection, and hardware failure. There is no difference in
      the outcomes of fractures treated with and without the use of a fracture table.
      This is particularly useful in the patient with multiple injuries for whom
      transfer to a fracture table may not be time effective.

PMID- 10088840
TI  - Spiral bundle nailing for subcapital humeral fractures: preliminary report of the
      method of Henning.
AB  - This is a preliminary report of 31 patients treated with Henning's spiral bundle
      nails for subcapital humeral fractures. Complications included motion restriction
      at the elbow joint (n = 4), elbow pain caused by pin migration (n = 2),
      misalignment attributable to incorrect reduction (n = 4), and redislocation
      attributable to improper technique (n = 1), humeral head perforation (n = 3),
      caudal subluxation of the humeral head (n = 3), and local infections at the
      insertion site (n = 1). Immobilization was 3 weeks on average. By using the
      scoring scheme of Constant and Murley, 11 patients showed a moderate result,
      whereas 19 patients had an excellent outcome.

PMID- 10088841
TI  - Biomechanical analysis of dynamic external fixation devices for the treatment of
      distal radial fractures.
AB  - BACKGROUND: Several dynamic external fixation devices have been introduced to
      permit early functional treatment of unstable distal radial fractures. METHODS:
      An intact cadaver wrist was spanned by a dynamic external fixator. Forces between
      the fixator and the radius were recorded during passive motion using a single,
      strain-gauged pin. A device with a double ball joint was compared with a new,
      experimental fixator with 3 degrees of freedom and its center of rotation
      coincident with that of the wrist. RESULTS: During flexion and extension, the pin
      load was approximately the same for both fixators. Radioulnar deviation resulted
      in high pin loads for the fixator with ball joints; the new device showed no
      considerable pin load. CONCLUSION: The new device has a high degree of kinematic
      compatibility with the natural wrist joint. When used for the treatment of distal
      radial fractures, it should provide favorable conditions for the maintenance of
      fracture reduction compared with a device with an offset ball joint.

PMID- 10088842
TI  - Estimation of defect volume in segmental defects of the tibia and femur.
AB  - BACKGROUND: With the advent of modern limb salvage techniques, segmental bone
      loss in the lower extremity has become more common. METHODS: To aid preoperative
      planning when dealing with segmental bone loss in the femur and tibia, we
      performed a cadaveric study to estimate the volume of autogenous or allograft
      material required to fill defects located in various areas of the bones. RESULTS:
      The greatest volume was generally required in metaphyseal defects, with an
      average of 12 cc/cm in the distal femur and proximal tibia, 11 cc/cm in the
      proximal femur, and 6 cc/cm in the distal tibia. Diaphyseal defects were found to
      have the least variability with regard to the volume of graft material required
      for different specimens. Femoral diaphyseal defects required 7 cc/cm and tibial
      diaphyseal defects required 5 cc/cm. A slightly larger volume of allograft
      material was needed to fill all defects compared with autograft. CONCLUSION: This
      method allows one to estimate the amount of graft required for a defect of the
      femur and the tibia.

PMID- 10088843
TI  - Hypertonic saline dextran attenuates leukocyte accumulation in the liver after
      hemorrhagic shock and resuscitation.
AB  - BACKGROUND: Hemorrhagic shock and resuscitation triggers a global
      ischemia/reperfusion phenomenon, in which activated leukocytes are considered
      strong contributors to the ensuing tissue damage. METHODS: The aim of the study
      was to investigate the effects of hypertonic saline dextran (HSD) on the early
      leukocyte/endothelial interactions (intravital fluorescence microscopy) in a rat
      model of hemorrhagic shock (1 hour at mean arterial pressure of 40 mm Hg). The
      resuscitation was performed with lactated Ringer's solution (RL, four times shed
      blood/20 minutes, n = 6), 6% dextran 60 (DEX, 100% shed blood/5 minutes, n = 8),
      and 7.2% NaCl/10% dextran 60 (HSD, 10% shed blood/2 minutes, n = 8). RESULTS:
      After 1 hour of resuscitation, shock-induced stasis/adherence of leukocytes was
      further enhanced with RL (sinusoids 17.6+/-6.9%; venules 33.9+/-8.5%), whereas
      DEX and HSD attenuated leukocyte stagnation in sinusoids (DEX -7.4+/-6,1%; HSD 
      14.7+/-2.9%, p<0.01 vs. RL) and leukocyte adherence in postsinusoidal venules
      (DEX -12.2+/-8.6%, p<0.05 vs. RL; HSD -27+/-7.4%, p<0.01 vs. RL). CONCLUSION: HSD
      reduced significantly the number of leukocytes accumulated in the liver after
      resuscitation of hemorrhagic shock, probably due to a combination of mechanisms
      of both components.

PMID- 10088844
TI  - Carboxyhemoglobin elevation in trauma victims.
AB  - BACKGROUND: Products of the hemeoxygenase enzyme include carboxyhemoglobin (COH)
      and bilirubin, which have protective effects in stressed states. Hemeoxygenase-1
      enzyme up-regulates in states of oxidative stress. We hypothesized that COH is
      elevated in septic trauma patients compared with nonseptic patients. METHODS: A
      prospective study was carried out at a Level I trauma center involving all
      patients admitted to the trauma intensive care unit. During a 3.5-month period,
      45 patients were enrolled, with 76 samples being drawn on admission and at later
      time points. The samples were classified as septic (Bone's criteria), stressed
      (based on expired gas analysis), or nonstressed nonseptic. Correlations with
      Acute Physiology and Chronic Health Evaluation III score, white blood cell count,
      temperature, partial pressure of oxygen, and percentage of inspired oxygen were
      evaluated. RESULTS: COH levels in samples drawn from patients presenting in shock
      (systolic blood pressure < or =90 mm Hg) were significantly higher than levels in
      samples from patients not in shock (systolic blood pressure >90 mm Hg) (3.27+/
      1.09 vs. 2.75+/-0.64; p = 0.013). Samples from septic patients with infection
      were associated with significantly higher Injury Severity Scores (34.1+/-11.2 vs.
      21.8+/-18.3; p< or =0.05) and a lower percentage of inspired oxygen (41.6+/-10.3
      vs. 61.0+/-26.3; p< or =0.05). CONCLUSION: COH was significantly elevated in
      samples drawn during stress, sepsis, and shock states. There was overlap between
      sepsis and stress COH sample values, limiting the clinical usefulness of the
      assays in predicting sepsis. Further studies focusing on hemeoxygenase-1
      expression and the role of its by-products in the outcomes of trauma patients are
      warranted.

PMID- 10088845
TI  - Pathogenesis of early cardiac myocyte damage after severe burns.
AB  - BACKGROUND: The importance of early cardiac myocyte damage during postburn trauma
      has been emphasized in recent years. However, its pathogenesis, prevention, and
      treatment have not been fully clarified. The aim of this study is to define its
      pathogenesis. METHODS: Rats with 30% third-degree burns were used. Cardiac
      biochemical markers reflecting cardiac myocyte damage including troponin T,
      cardiac myosin light chain 1, creatinine kinase and its cardiac-specific
      isoenzyme compound, as well as inflammatory mediators such as tumor necrosis
      factor, endothelin/nitric oxide ratio, malondialdehyde, and superoxide dismutase,
      were determined. RESULTS: Cardiac biochemical markers reflecting cardiac myocyte
      damage, including troponin T, cardiac myosin light chain 1, cardiac-specific
      isoenzyme compound, were all significantly elevated between 3 hours and 24 hours
      after burn. Changes in tumor necrosis factor, endothelin/nitric oxide ratio, and
      malondialdehyde were similar to those of cardiac biochemical markers. In
      contrast, levels of superoxide dismutase declined markedly after burn.
      CONCLUSION: The findings of this study showed that considerable amounts of
      myocardial constructive protein degradation and release due to destruction of
      cardiac myocytes occurred early after severe burns. The inflammatory mediators
      released after burn injury may be involved in the pathogenesis of myocardial
      destruction.

PMID- 10088846
TI  - Multicenter trial to evaluate the safety and potential efficacy of pooled human
      fibrin sealant for the treatment of burn wounds.
AB  - OBJECTIVE: The primary purpose of this multicenter study was to evaluate the
      safety and potential efficacy of a solvent/detergent-treated commercial fibrin
      sealant (human) for topical hemostasis in skin grafting. METHODS: The study
      involved a prospective evaluation of changes in viral titers in patients with
      burns less than 15% after treatment with fibrin sealant (human). Each patient
      served as his/her own control for an unblinded, randomized comparison of donor
      site hemostasis and healing. Preoperative serum was obtained to screen for viral
      titers. At autografting, the recipient site and one of two randomly chosen donor
      sites were treated with fibrin sealant (human). The use of other hemostatic
      agents, including epinephrine was prohibited. Each donor site was covered with
      gauze to collect blood for estimation of the relative amount of bleeding. The
      healing of the graft and donor sites was observed. Viral titers and wounds were
      checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS:
      Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein
      Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47
      patients, 34 completed the full year of observation. After treatment, there were
      no seroconversions to any of the aforementioned viruses. Bleeding at the
      recipient site appeared well controlled with fibrin sealant (human). Although
      investigators felt that fibrin sealant (human) improved donor site hemostasis,
      differences in hemoglobin measurements of blood-soaked dressings failed to reach
      significance. No differences were noted with regard to acceleration of donor site
      healing, graft take, or scar maturation at the two groups of donor sites.
      Anecdotally, the maturation of the recipient site appeared to be accelerated.
      CONCLUSION: Fibrin sealant (human) is safe for use during excision and grafting,
      and its topical hemostatic potential needs to be examined in patients with larger
      burns. Its role in scar maturation also needs to be investigated.

PMID- 10088847
TI  - Comparison of staples versus sutures in the repair of penetrating cardiac wounds.
AB  - BACKGROUND: Several literature reports advocate the use of skin staplers for
      repair of penetrating cardiac wounds during emergency thoracotomy. Our study goal
      was to objectively determine if stapling is a more efficient method of closure
      compared with suturing without compromising the strength of the repair. METHODS:
      This randomized, nonblinded study was conducted in a swine model. A total of four
      incisions, two per ventricle, were made in each animal. The 2-cm full-thickness
      incisions were repaired with either sutures or staples, and the time required to
      close each wound was recorded. After wound repair, the animals were killed. The
      four wounds were isolated by removing 4.0-cm strips of myocardium oriented
      perpendicular to the incision. Each strip was then placed on a tensile force
      testing machine, and the breaking strength of the sutures and staples was
      measured. RESULTS: The tensile force test showed that stapled and sutured wounds
      have equivalent mechanical strength. The mean time of closure for stapled wounds
      was substantially less than that for sutured wounds. CONCLUSION: In this swine
      model, stapling took significantly less time and had equal mechanical strength
      compared with suturing for repair of penetrating cardiac wounds. Stapling during
      emergent resuscitation may be preferable to suturing.

PMID- 10088848
TI  - Blunt versus penetrating subclavian artery injury: presentation, injury pattern,
      and outcome.
AB  - BACKGROUND: Subclavian artery (SCA) injuries are rare vascular injuries and may
      be difficult to manage. The majority of SCA injuries are secondary to penetrating
      trauma. The purpose of this report is to examine the injury patterns, diagnostic
      and therapeutic approaches, and outcome of patients with blunt and penetrating
      SCA injuries. METHODS: Retrospective review RESULTS: Fifty-six patients sustained
      SCA injuries (25 blunt, 31 penetrating). SCA injury location was evenly
      distributed between the proximal, middle, and distal SCA after penetrating
      trauma; proximal injuries were rare (2 of 25) with blunt mechanisms. A radial
      arterial pulse deficit was present in only 3 of 25 blunt injuries and 9 of 31
      penetrating injuries. Complications occurred more commonly in both groups of
      patients with initial systolic blood pressures less than 90 mm Hg. Survival was
      76% in blunt and 81% in penetrating groups; limb salvage was similar (92% in
      blunt and 97% in penetrating groups). Complete brachial plexus injuries were more
      common with blunt injuries. CONCLUSION: SCA injuries are rare vascular injuries
      with an associated high morbidity and mortality, regardless of mechanism. Blunt
      mechanisms result in more middle and distal injuries and more frequent complete
      brachial plexus injuries. Complications are related to the hemodynamic status of
      the patient upon presentation, and not to mechanism of injury.

PMID- 10088849
TI  - Association of head trauma with cervical spine injury, spinal cord injury, or
      both.
AB  - BACKGROUND: Links between cervical spine and/or spinal cord injuries and head
      trauma have not been reported in detail. METHODS: 188 patients with cervical
      spine and/or spinal cord injury were divided into two groups, i.e., with upper
      cervical and mid-lower cervical injury, and compared for head injury. RESULTS:
      Associated head trauma was investigated in 188 patients with cervical spine
      and/or spinal cord injuries; 35% had moderate or severe injuries. Brain damage
      was more frequently observed in patients with upper cervical injury than in those
      with mid to lower cervical injury. Those patients with upper cervical injury
      appeared to have an elevated risk of suffering skull base fractures, traumatic
      subarachnoid hemorrhage, and contusional hemotoma. CONCLUSIONS: Approximately one
      third of patients with cervical spine and/or spinal cord injuries had moderate or
      severe head injuries. Brain damage was more frequently associated with upper
      cervical injury. Those patients with upper cervical injury are at greater risk of
      suffering from skull base fractures and severe intracranial hematomas than those
      with mid to lower cervical injury.

PMID- 10088850
TI  - Low falls: an underappreciated mechanism of injury.
AB  - OBJECTIVE: This is a retrospective study designed to evaluate the pattern and
      severity of injuries that result from low falls, defined as falls from less than
      20 ft, subsequent mortality, and requirements of hospital resources. Our
      hypothesis is that many of these injuries, even without cardiopulmonary
      instability, are worthy of trauma center care. METHODS: The records of all
      patients entered into the hospital trauma registry at an urban Level I trauma
      center during the years 1991 through 1997 who suffered low falls and who either
      died after admission or were hospitalized for at least 3 days were reviewed.
      Patients suffering isolated hip fractures were excluded. One hundred seventy-six
      patients constituted the study population. This group accounts for about 2% of
      all admissions for falls at our institution. Patterns of injury were examined.
      Age, mechanism of injury, Injury Severity Score (ISS), and cardiopulmonary or
      neurologic instability on admission were documented. Mortality, length of
      intensive care unit and hospital stays, as well as billed hospital charges, were
      reviewed. RESULTS: The majority of patients (62%) were younger than 50 years.
      Sixty patients had ISS >15 and 116 patients had ISS >9. Sixty patients had
      multisystem injuries requiring specialty care. Head injuries were found in 81
      patients (35%), and vertebral fractures or spinal cord injuries were found in 49
      patients (22%), including 9 quadriplegics and 5 paraplegics. There were seven
      patients with intra-abdominal injuries (five spleen and two bowel injuries).
      There was one patient with a rupture of the thoracic aorta. Seventeen patients
      had deteriorating neurologic or pulmonary function on arrival, but the majority
      (90%) were stable. Of the 159 "stable" patients, 48 suffered head injuries, 7
      were quadriplegic, and 3 were paraplegic. All intra-abdominal injuries were in
      this group. Overall, 14 of 176 patients (8%) died. Seven deaths were in patients
      older than 60 years, and seven deaths were in younger patients (p = 0.04). The
      majority of deaths (9 of 14) were from head trauma. Care in the intensive care
      unit was required in 92 of 176 patients. Nine patients had billed charges
      exceeding $100,000. CONCLUSION: Low falls can cause significant injuries, most
      commonly to the head and spine. Based on mechanism of injury alone, patients
      injured in low falls might not be taken to trauma centers. We have found,
      however, that many of these patients sustain serious multisystem injuries, even
      though they are stable initially. Although these patients represent only a
      fraction of those who fall, our study would support adjustment of triage
      guidelines to recommend transport of such patients, particularly elderly
      patients, to trauma centers.

PMID- 10088851
TI  - Fatal injury: characteristics and prevention of deaths at the scene.
AB  - BACKGROUND: Almost half of all trauma deaths occur at the scene. It is important
      to determine if these deaths can be prevented. METHODS: Penetrating or blunt
      force trauma deaths were identified through the Office of the Medical Examiner
      during a 2-year period. Data were also obtained through review of these records.
      RESULTS: There were 312 deaths at the scene that received no medical care. Almost
      60% were firearm-related. About 80% of the victims were men, and 55% of these
      deaths occurred in people between 20 and 49 years old. Suicide accounted for
      nearly half of these deaths. Eighty percent of these injured people had
      Abbreviated Injury Scale scores of 5 or 6. CONCLUSION: Almost 60% of deaths at
      the scene occurred at the same time as injury and reflect severe injury to vital
      regions of the body. These findings suggest that primary prevention of the
      initial event causing injury may be more important than definitive prehospital
      emergency medical care to prevent these deaths.

PMID- 10088853
TI  - Focused Assessment with Sonography for Trauma (FAST): results from an
      international consensus conference.
AB  - OBJECTIVE: To assemble an international panel of experts to develop consensus
      recommendations on selected important issues on the use of ultrasonography (US)
      in trauma care. SETTING: R Adams Cowley Shock Trauma Center, University of
      Maryland Medical System, Baltimore, Md. The conference was held on December 4,
      1997. PARTICIPANTS: A committee of two co-directors and eight faculty members, in
      the disciplines of surgery and emergency medicine, representing four nations.
      Each faculty member had made significant contributions to the current
      understanding of US in trauma. RESULTS: Six broad topics felt to be controversial
      or to have wide variation in practice were discussed using the ad hoc process:
      (1) US nomenclature and technique; (2) US for organ-specific injury; (3) US
      scoring systems; (4) the meaning of positive and negative US studies; (5) US
      credentialing issues; and (6) future applications of US. Consensus
      recommendations were made when unanimous agreement was reached. Majority
      viewpoints and minority opinions are presented for unresolved issues. CONCLUSION:
      The consensus conference process fostered an international sharing of ideas.
      Continued communication is needed to advance the science and technology of US in
      trauma care.

PMID- 10088852
TI  - Gunshot wounds: bullet caliber is increasing.
AB  - BACKGROUND: The incidence of gunshot wounds has increased over the past two
      decades. In the past several years at our Level I trauma center in Newark NJ, we
      perceived that the size of ammunition involved in these wounds has been
      increasing as well. We sought to document this trend by using autopsy data as
      well as bullets received by surgical pathology. METHODS: Measurements of bullets
      stored in surgical pathology were taken from alternate years between 1981 and
      1993, then every year through 1997. A total of 745 bullets were studied in this
      16-year period. Bullets deformed beyond measurability and shotgun pellets were
      excluded from the study (approximately 20%). Linear regression of mean bullet
      caliber over time was performed, and analysis of variance was used to assess
      statistical significance of apparent differences. In addition, autopsy reports
      from the regional medical examiner's office were surveyed for description of
      bullet size. Bullet caliber, in these reports, is described as "small," "medium,"
      or "large." A total of 397 reports were studied from 1981 to 1997. Once again,
      shotgun wounds (<5%) were excluded. The percentage of large-caliber projectiles
      was plotted against time, and chi2 for trend was used to determine statistical
      significance. RESULTS: Results are tabulated as mean +/- standard error bullet
      caliber (millimeters) over time. Linear regression reveals r = 0.944, p<0.0001.
      Data obtained from autopsy reports are not tabulated here, but chi2 for trend
      reveals a statistically significant increase in the proportion of large caliber
      and decrease in proportion of small-caliber bullets (p<0.001). CONCLUSION: These
      data unveil an ominous trend toward the use of larger-caliber firearms in
      accidents, homicides, and suicides.

PMID- 10088854
TI  - Defining excess resource utilization and identifying associated factors for
      trauma victims.
AB  - BACKGROUND: Trauma system evaluation addresses aspects of the process, structure,
      and outcomes of trauma care. This approach may not identify all opportunities for
      trauma system improvement. Hospital length of stay (LOS) represents a meaningful
      measure of resource utilization and may help focus efforts to improve care. The
      purpose of this study is to estimate expected hospital LOS after trauma and
      determine the consequences of excessive LOS. METHODS: Patients admitted during a
      2-year period (January 1, 1993 to December 31, 1994) were retrospectively
      reviewed, and expected LOS was estimated. Excess LOS was defined as an observed
      LOS > or =100% of expected. Injuries, complications, and American College of
      Surgeons' Committee on Trauma audit filters were compared between the groups.
      RESULTS: Observed LOS exceeded expected by 100% or more for 568 of 5,226 patients
      (10.9%), and most survived (98.3%). Complications predicted excess LOS, whereas
      audit filters did not. Median costs for these 568 patients were $30,315 and
      totaled 30% of the expenditures for the entire cohort of 5,226 patients.
      CONCLUSION: Prolonged LOS represents an adverse outcome. Estimation of LOS and
      evaluation of outliers represents an important method for the evaluation of care
      within established trauma systems and centers.

PMID- 10088855
TI  - Trauma recurrence in the pediatric emergency population.
AB  - BACKGROUND: A link between ambulatory trauma and trauma recurrence may be
      hypothesized: (a) children who present for trauma may be those with
      characteristics that place them at particular risk; (b) children who frequently
      present for trauma may be those who present because of parental anxiety; and (c)
      children may learn from traumatic episodes and therefore decrease their trauma
      risk. METHODS: A retrospective chart review of billing data was conducted to
      determine the value of the emergency department trauma visit count as a predictor
      of future trauma visits and to validate one of the models described above.
      RESULTS: Records for 16,994 patients were obtained for the period January 1
      through December 31, 1997, and these patients were followed as a cohort through
      the first 6 months of 1998. There were 9,236 males and 7,757 females. Of these,
      5,413 patients had a trauma visit count in 1997 (TC97) of at least 1; 120
      patients had a TC97 of 3 or more. The relationship between TC97 and trauma visit
      count in 1998 was linear, present in both males and females and across all age
      categories, with odds ratios for the group with TC97 > or =3 ranging from 3.8 to
      6.4. Conversely, the risk of presentation with respiratory tract infection during
      the study period in 1998 was not increased with higher TC97 values. CONCLUSION:
      Our data support the theory that children who present with trauma tend to be
      those with extrinsic or intrinsic factors that increase trauma risk. We have
      demonstrated a direct relationship between emergency department visit counts for
      trauma with future trauma occurrence risk. This relationship is present at all
      ages and in both males and females. The emergency trauma visit count is an easily
      obtained measure that has merit as an index to identify higher-risk children for
      possible intervention strategies. Further work is needed.

PMID- 10088856
TI  - Financial aspects of providing trauma care at the extremes of life.
AB  - BACKGROUND: Children and the elderly are more likely to be underinsured compared
      with the general population of trauma patients. We performed financial analysis
      on all trauma patients admitted during an 18-month period to a Level I adult and
      pediatric trauma center to evaluate the financial impact of providing trauma care
      for children and the elderly. METHODS: Patients were categorized by age: PEDI<17
      years, GERI>64 years and MID = 17 to 64 years. Reimbursement ratio (RR =
      reimbursement/cost; RR>1 = profit, RR<1 = loss), length of stay (LOS), and Injury
      Severity Score (ISS) were calculated for each age group. RESULTS: RR for GERI (RR
      = 0.99) was significantly lower than for PEDI (RR = 1.15) and MID (RR = 1.16).
      There was no difference in ISS, but the LOS of GERI was greater than that of PEDI
      and MID (p<0.05). Cost per patient and LOS were less in PEDI versus MID and GERI
      (p<0.05). CONCLUSION: Trauma care reimbursement for the elderly is inadequate,
      whereas pediatric trauma care costs less to deliver and is profitable to the
      trauma center.

PMID- 10088857
TI  - Consolidation of trauma programs in the era of large health care delivery
      networks.
AB  - OBJECTIVE: To review the development of an integrated trauma program at two
      separate campuses brought about by the merger of two medical-affiliated
      hospitals, each with an integrated program and a common trauma administrator,
      medical director, and educational coordinator. Each campus has an associate
      trauma medical director for on-site administrative management, a nurse
      coordinator, and a registrar. The integration resulted in a reduction of 1.5 full
      time equivalents and "cost" savings by consolidated use of the helicopter,
      outreach, prevention, research, and educational programs. Regular "integration
      meetings," ad hoc committees, and video-linked conferences were used to institute
      common quality improvement programs, morbidity and mortality discussions,
      policies, and clinical management protocols. Reaccreditation by an outside
      agency, elimination of duplicated services, and maintenance of pre-merger
      clinical volume results. CONCLUSION: This integrated trauma program may serve as
      a model in this era of individual hospitals merging into large health care
      delivery networks.

PMID- 10088858
TI  - Eye injuries in patients with major trauma.
AB  - BACKGROUND: A study was performed to determine the type and frequency of ocular
      injuries in patients with major trauma. METHODS: All patients with ocular and
      adnexal injuries (n = 178) among 1,119 patients admitted with major trauma
      (Injury Severity Score >15) to the Royal Prince Alfred Hospital from July 1990 to
      December 1997 were analyzed. RESULTS: Sixteen percent of the major trauma cohort
      had ocular or orbital trauma. Fifty-five percent of patients with injuries
      involving the face had ocular or orbital injuries. A range of ocular injuries was
      seen. Analysis of the major trauma cohort showed that motor vehicle drivers,
      orbital and base of skull fractures, eyelid lacerations, and superficial eye
      injuries were strongly associated with vision-threatening injury. CONCLUSION:
      Patients with major trauma and facial injuries have a high risk of vision
      threatening injury. Patients with orbital fractures, base of skull fracture,
      eyelid lacerations, and superficial eye injuries should be assessed by an
      ophthalmologist as part of the early management of their trauma to determine
      whether an ocular injury is present.

PMID- 10088859
TI  - Bilateral traumatic hip dislocation in a child: a case report and review of the
      literature.

PMID- 10088860
TI  - Tracheobronchial avulsion and associated innominate artery injury in blunt
      trauma: case report and literature review.

PMID- 10088861
TI  - Traumatic hernia of the pericardium.

PMID- 10088862
TI  - Severe pulmonary contusion with traumatic ventricular septal defect rescued using
      percutaneous cardiopulmonary support.

PMID- 10088863
TI  - The tensor fascia lata free flap in staged abdominal wall reconstruction after
      traumatic evisceration.

PMID- 10088864
TI  - Management of proximal interphalangeal joint injuries.

PMID- 10088865
TI  - Intracardiac chest tube placement.

PMID- 10088866
TI  - Lower limb trauma caused by power-driven cultivators: report of 23 cases.

PMID- 10088867
TI  - Traumatic aortic and diaphragmatic rupture in a patient with situs inversus.

PMID- 10088868
TI  - Ruptured lumbar artery pseudoaneurysm: a diagnostic dilemma in retroperitoneal
      hemorrhage after abdominal trauma.

PMID- 10088869
TI  - Increased concentration of vascular endothelial growth factor (VEGF) in chronic
      subdural hematoma.

PMID- 10088870
TI  - Lentigo maligna melanoma and excisional biopsy techniques.

PMID- 10088871
TI  - Potentially fatal natural remedies.

PMID- 10088872
TI  - Does estrogen therapy have a role in cardiovascular prevention?

PMID- 10088873
TI  - Gastroesophageal reflux disease: diagnosis and management.
AB  - Gastroesophageal reflux disease (GERD) is a chronic, relapsing condition with
      associated morbidity and an adverse impact on quality of life. The disease is
      common, with an estimated lifetime prevalence of 25 to 35 percent in the U.S.
      population. GERD can usually be diagnosed based on the clinical presentation
      alone. In some patients, however, the diagnosis may require endoscopy and,
      rarely, ambulatory pH monitoring. Management includes lifestyle modifications and
      pharmacologic therapy; refractory disease requires surgery. The therapeutic goals
      are to control symptoms, heal esophagitis and maintain remission so that
      morbidity is decreased and quality of life is improved.

PMID- 10088874
TI  - When to consider radiation therapy for your patient.
AB  - Radiation therapy can be an effective treatment modality for both malignant and
      benign disease. While radiation can be given as primary treatment, it may also be
      used pre- or postoperatively, with or without other forms of therapy. Radiation
      therapy is often curative but is sometimes palliative. There are many methods of
      delivering radiation effectively. Often, patients tolerate irradiation well
      without significant complications, and organ function is preserved. To ensure
      that all patients with cancer have the opportunity to consider all treatment
      options, family physicians should be aware of the usefulness of radiation
      therapy.

PMID- 10088875
TI  - Congenital adrenal hyperplasia: not really a zebra.
AB  - Congenital adrenal hyperplasia was once considered a rare inherited disorder with
      severe manifestations. Mild congenital adrenal hyperplasia, however, is common,
      affecting one in 100 to 1,000 persons in the United States and frequently eluding
      diagnosis. Both classic and nonclassic forms of the disease are caused by
      deficiencies in the adrenal enzymes that are used to synthesize glucocorticoids.
      The net result is increased production from the adrenal gland of cortisol
      precursors and androgens. Even mild congenital adrenal hyperplasia can result in
      life-threatening sinus or pulmonary infections, orthostatic syncope, shortened
      stature and severe acne. Women with mild congenital adrenal hyperplasia often
      present with hirsutism, oligomenorrhea or infertility. Congenital adrenal
      hyperplasia is diagnosed by demonstration of excess cortisol precursors in the
      serum during an adrenal corticotropic hormone challenge. Diagnosis of congenital
      adrenal hyerplasia in fetuses that are at risk for congenital adrenal hyperplasia
      can be determined using human leukocyte antigen haplotype or by demonstration of
      excess cortisol precursors in amniotic fluid. Treatment includes carefully
      monitored hormone replacement therapy. Recognition of the problem and timely
      replacement therapy can reduce morbidity and enhance quality of life in patients
      that are affected by congenital adrenal hyperplasia.

PMID- 10088876
TI  - Primary nocturnal enuresis: current.
AB  - Primary nocturnal enuresis sometimes presents significant psychosocial problems
      for children and their parents. Causative factors may include maturational delay,
      genetic influence, difficulties in waking and decreased nighttime secretion of
      antidiuretic hormone. Anatomic abnormalities are usually not found, and
      psychologic causes are unlikely. Evaluation of enuresis usually requires no more
      than a complete history, a focused physical examination, and urine specific
      gravity and dipstick tests. Nonpharmacologic treatments include motivational
      therapy, behavioral conditioning and bladder-training exercises. Pharmacologic
      therapy includes imipramine, anticholinergic medication and desmopressin. These
      drugs have been used with varying degrees of success.

PMID- 10088877
TI  - Urinary tract infections in adults.
AB  - Urinary tract infections remain a significant cause of morbidity in all age
      groups. Recent studies have helped to better define the population groups at risk
      for these infections, as well as the most cost-effective management strategies.
      Initially, a urinary tract infection should be categorized as complicated or
      uncomplicated. Further categorization of the infection by clinical syndrome and
      by host (i.e., acute cystitis in young women, acute pyelonephritis, catheter
      related infection, infection in men, asymptomatic bacteriuria in the elderly)
      helps the physician determine the appropriate diagnostic and management
      strategies. Uncomplicated urinary tract infections are caused by a predictable
      group of susceptible organisms. These infections can be empirically treated
      without the need for urine cultures. The most effective therapy for an
      uncomplicated infection is a three-day course of trimethoprim-sulfamethoxazole.
      Complicated infections are diagnosed by quantitative urine cultures and require a
      more prolonged course of therapy. Asymptomatic bacteriuria rarely requires
      treatment and is not associated with increased morbidity in elderly patients.

PMID- 10088878
TI  - Herbal remedies: adverse effects and drug interactions.
AB  - A growing number of Americans are using herbal products for preventive and
      therapeutic purposes. The manufacturers of these products are not required to
      submit proof of safety and efficacy to the U.S. Food and Drug Administration
      before marketing. For this reason, the adverse effects and drug interactions
      associated with herbal remedies are largely unknown. Ginkgo biloba extract,
      advertised as improving cognitive functioning, has been reported to cause
      spontaneous bleeding, and it may interact with anticoagulants and antiplatelet
      agents. St. John's wort, promoted as a treatment for depression, may have
      monoamine oxidase-inhibiting effects or may cause increased levels of serotonin,
      dopamine and norepinephrine. Although St. John's wort probably does not interact
      with foods that contain tyramine, it should not be used with prescription
      antidepressants. Ephedrine-containing herbal products have been associated with
      adverse cardiovascular events, seizures and even death. Ginseng, widely used for
      its purported physical and mental effects, is generally well tolerated, but it
      has been implicated as a cause of decreased response to warfarin. Physicians must
      be alert for adverse effects and drug interactions associated with herbal
      remedies, and they should ask all patients about the use of these products.

PMID- 10088879
TI  - Hypertension treatment and the prevention of coronary heart disease in the
      elderly.
AB  - Both isolated systolic hypertension (>140 mm Hg/<90 mm Hg) and systolic/diastolic
      hypertension (>140 mm Hg/>90 mm Hg) are major risk factors for cardiovascular
      disease in the elderly. Specific antihypertensive drug therapy is available if
      lifestyle interventions fail to reduce blood pressure to a normal level.
      Diuretics and beta blockers both reduce the occurrence of adverse events related
      to cerebrovascular disease; however, diuretics are more effective in reducing
      events related to coronary heart disease. Treated patients are less likely to
      develop severe hypertension or congestive heart failure. In most instances, low
      dose diuretic therapy should be used as initial antihypertensive therapy in the
      elderly. A long-acting dihydropyridine calcium channel blocker may be used as
      alternative therapy in elderly patients with isolated systolic hypertension.
      Trials are being conducted to evaluate the long-term effects of angiotensin
      converting enzyme inhibitors and angiotensin-II receptor blockers in elderly
      patients with uncomplicated hypertension.

PMID- 10088880
TI  - Photo quiz. A palmar rash.

PMID- 10088881
TI  - Suspected abuse in an elderly patient.

PMID- 10088882
TI  - CDC issues new recommendations for the prevention and control of hepatitis C
      virus infection.

PMID- 10088883
TI  - Abacavir for treatment of HIV infection.

PMID- 10088884
TI  - Symposium on distortion and structural deterioration of endovascular grafts used
      to repair abdominal aortic aneurysms. Introduction.

PMID- 10088885
TI  - Shortening of endografts during deployment in endovascular AAA repair.
AB  - PURPOSE: To evaluate the incidence and extent of length changes during
      implantation of endovascular grafts in a prospective study of patients undergoing
      endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Data regarding the
      occurrence of intraoperative technical difficulties and device complications were
      recorded prospectively for the Vanguard or AneuRx self-expanding, bifurcated
      endovascular grafts in 64 patients (56 males; mean age 75 years). Graft length
      was measured in the sheath system before deployment and again immediately after
      deployment by fluoroscopic comparison to a graduated marking catheter. RESULTS:
      Graft shortening > or = 15 mm was documented in 22 (56%) of 39 Vanguard cases and
      11 (44%) of 25 AneuRx endografts. Additional extension grafts were required to
      correct endoleak caused by inadequate graft length in 9 (14%) patients, but no
      conversion to open repair was necessary. CONCLUSIONS: There appears to be a high
      incidence of intraprocedural graft shortening with 2 current designs of self
      expanding endoluminal grafts.

PMID- 10088886
TI  - Longitudinal aneurysm shrinkage following endovascular aortic aneurysm repair: a
      source of intermediate and late complications.
AB  - PURPOSE: To report the incidence of delayed complications following endovascular
      abdominal aortic aneurysm (AAA) repair and the relationship of these sequelae to
      morphological changes in the sac and endograft. METHODS: Twenty-six AAA patients
      treated with Vanguard endografts had completed > or = 1-year follow-up.
      Postoperative angiograms and spiral computed tomographic (CT) scans with 3
      dimensional reconstruction were compared to the 1-year images to determine
      morphological changes in the aneurysm sac and the endograft. These changes were
      then related to complications occurring between 1 and 12 months postoperatively
      in the study group. RESULTS: Comparison of angiograms uncovered endograft
      buckling in 18 (69%) patients and acutely angled or kinked endografts in 10
      (38%). Measurements from the CT scans found that undistorted endografts had a
      mean change in sac length of +6.6 mm. Mean sac length change in buckled
      endografts was -3.1 mm, while kinked endografts displayed a mean change of -6.2
      mm (p < 0.002, Student's t-test). Five (19%) patients, all with distorted
      endografts, demonstrated late (1 to 12 months) complications (4 endoleaks and 1
      graft limb thrombosis) owing to component separation, distal stent migration, and
      acute angulation. No movement in the proximal stent was observed. Elongation of
      the endograft (flow line measurement) was observed in one tube graft only.
      CONCLUSIONS: In this study, longitudinal shrinkage of the sac following
      endovascular aortic aneurysm repair led to buckling or kinking of the endograft
      within 1 year in 69% of patients. This appears to be an important source of
      delayed complications.

PMID- 10088887
TI  - Time-related alterations in shape, position, and structure of self-expanding,
      modular aortic stent-grafts: a 4-year single-center follow-up.
AB  - PURPOSE: To report the nature and ramifications of structural and positional
      changes over time in tube and modular bifurcated aortic stent-grafts. METHODS:
      Two hundred ninety-one patients received endovascular aortic grafts (primarily
      Stentor/Vanguard) between August 1994 and August 1998. Follow-up surveillance
      (clinical and laboratory examination, biplanar noncontrast radiography, and
      contrast-enhanced computed tomography) has been maintained on all patients for 4
      years. Changes in the configuration and position of endografts have been noted
      and their sequelae charted. RESULTS: Three types of endograft shape changes have
      been documented: mild -- slight distortions visible on plain radiographs (n = 90,
      31.0%), significant -- angulations reaching 60 degrees to 90 degrees (n = 65,
      22.3%), and severe -- angulations > or = 90 degrees (n = 10, 3.4%). Changes in
      position never gave rise to late migration at the proximal attachment site,
      whereas at the distal ends, the endograft easily retracted from the iliac
      arteries (n = 8). Structural alterations (rupture of the stent frame, sutures, or
      fabric, and total graft disintegration) were more common in the original Stentor
      model. Shape, position, and structural alterations were mutually dependent and
      led to secondary endoleaks (n = 26) and graft limb thrombosis (n = 37). Late
      surgical conversion was necessary in 3 (1.0%) patients. CONCLUSIONS: Tortuosity
      of the native vessels is a source of complication in long-term follow-up just as
      it is during implantation. Given the late appearance of complications in this
      patient cohort, it would seem that the durability of an endograft cannot be
      evaluated with < 3 years of follow-up.

PMID- 10088888
TI  - Percutaneous transluminal angioplasty of the subclavian arteries.
AB  - PURPOSE: To review the feasibility, risks, and long-term results of subclavian
      artery angioplasty with and without Palmaz stent placement. METHODS: Over a 9
      year period, 113 patients (67 males; mean age 63 +/- 13 years) underwent
      percutaneous balloon angioplasty of subclavian occlusive lesions for a variety of
      indications: vertebrobasilar insufficiency (n = 70), upper limb ischemia (n =
      50), coronary steal syndrome (n = 6), or anticipated coronary artery bypass
      grafting using the internal mammary artery in 12 asymptomatic patients. There
      were 94 (83%) stenoses and 19 (17%) occlusions with a mean percent stenosis of
      80.1% +/- 7.4% (range 70 to 100). Mean lesion length was 24 +/- 8 mm (range 10 to
      50). Beginning in 1989, stents were implanted for suboptimal dilation; in 1995,
      stenting became routine. RESULTS: Overall, 103 (91%) of 113 lesions were
      successfully treated; 10 (53%) occlusions could not be recanalized. Fifty-one
      stents were implanted in 46 patients. There were 3 (2.6%) procedural
      complications: a transient ischemic attack, one major (fatal) stroke, and an
      arterial thrombosis 24 hours after the procedure (treated medically) (0.9% major
      stroke and death rate). During a mean 4.3-year follow-up (range to 10), 16
      (15.5%) restenoses were treated with angioplasty (n = 4), stenting (n = 7), or
      surgery (n = 5). Primary and secondary patencies for all treated lesions (n =
      113) at 8 years were 75% and 81%, respectively; in patients without initial stent
      placement, the rates were 69% and 76%, while in those with stents, the rates rose
      slightly to 87% and 94% at 2.5 years (NS). Patency rates for all 103 recanalized
      lesions were 83% and 90% at 8 years (81% and 90% without stent and 87% and 94%
      with stent at 2.5 years, respectively [NS]). CONCLUSIONS: Balloon angioplasty
      with or without stenting is safe and effective for treating subclavian artery
      occlusive diseases with good long-term patency. Recanalization of occlusions is
      more difficult to achieve. Stents (implanted only for suboptimal dilation) do not
      seem to improve long-term patency.

PMID- 10088889
TI  - Stents in the treatment of renal artery stenosis: long-term follow-up.
AB  - PURPOSE: To evaluate the role of percutaneous stenting in the treatment of renal
      arterial lesions after failure of balloon angioplasty. METHODS: Two hundred ten
      patients (139 males; mean age 67.7 +/- 9.9 years, range 27 to 87) had 259 balloon
      expandable stents (165 Palmaz and 94 Renal Bridge stents) implanted in 244 renal
      artery stenoses (171 ostial and 73 nonostial lesions). The patients were
      suffering from intractable hypertension (n = 210) and/or renal dysfunction (n =
      48). The majority of the lesions (n = 234) were atheromatous in origin. Stents
      were implanted for suboptimal balloon dilation (n = 182, 75%), restenotic lesions
      (n = 27, 11%), or dissection (n = 9, 4%); 26 (11%) ostial lesions were stented
      primarily. Mean lesion length was 11.9 +/- 4.4 mm (range 5 to 30) and mean
      percent stenosis was 81.9% +/- 8.25% (range 70 to 100). RESULTS: Immediate
      technical success was 99% (241 of 244). Three (1.2%) major complications included
      one intraprocedural stent thrombosis, one arterial perforation manifesting as a
      perirenal hematoma 24 hours after the procedure, and one renal arterial rupture.
      Follow-up over a mean 25.4 +/- 22.8 months (range 1 to 96) in 185 eligible
      patients (209 arteries) found 24 cases of restenosis (11.4%). Primary and
      secondary patencies for all lesions at 60 months were 79% and 98%, respectively,
      with no significant differences between ostial and nonostial lesions or stent
      types. Hypertension was reversed in 35 (19%), improved in 112 (61%), and remained
      unchanged in 37 (20%). Renal function was improved in 29% (14 of 48), unchanged
      in 67% (32 of 48), and worse in 4% (2 of 48). CONCLUSIONS: Renal artery stenting
      is safe, effective, and may be an alternative to surgery, particularly in ostial
      lesions. Our experience shows reduction in the restenosis rate compared to
      conventional angioplasty. All ostial stenoses should be stented.

PMID- 10088890
TI  - Angioplasty of lower limb arterial stenoses under ultrasound guidance: single
      center experience.
AB  - PURPOSE: To examine the feasibility and utility of ultrasound-guided angioplasty
      for treating lower limb stenoses. METHODS: Duplex ultrasonography was employed to
      guide 55 balloon dilation procedures (27 iliac, 26 superficial femoral, 1
      profunda, and 1 vein graft) with the help of a special ultrasound catheter
      (EchoMark). Ultrasound was used to determine balloon size, monitor guidewire
      passage, direct the dilation, and judge procedural success. Angiography was
      performed prior to the procedure to confirm preprocedural ultrasound findings and
      afterward to compare with duplex visual and hemodynamic parameters of success
      (peak systolic velocity ratio < 2.0). RESULTS: The balloon size determined from
      duplex measurements correlated in all cases with sizes selected based on the
      angiographic image. Guidewire visualization was possible in 95% of the cases.
      Angioplasty using ultrasound alone was feasible in 84%; inability to obtain a
      satisfactory image owing to vessel tortuosity, calcification, and bowel gas
      accounted for the failures. Against the duplex success criterion, initial
      completion angiograms had an accuracy of 76%, sensitivity of 76%, and specificity
      of 100%. The additional time for ultrasound guidance averaged 42 +/- 12 minutes
      for all cases. CONCLUSIONS: Our results show that ultrasound guidance is feasible
      in routine clinical practice. In this series of well-selected cases of arterial
      stenoses, angioplasty was performed safely using ultrasound guidance alone in
      over 80% of the cases. Fluoroscopic monitoring is needed when ultrasound
      visualization is suboptimal.

PMID- 10088891
TI  - The role of carotid duplex ultrasound in evaluating plaque morphology: potential
      use in selecting patients for carotid stenting.
AB  - PURPOSE: To study the role of duplex ultrasonography in evaluating plaque
      morphology and its correlation to neurological symptoms and cerebral infarctions
      on computed tomographic scans. METHODS: The hospital records of 181 patients (107
      males; average age 66 years, range 41 to 89) with > 50% carotid stenosis (29
      bilateral lesions) who had undergone duplex ultrasonography, carotid
      arteriography, and cerebral computed tomography were studied retrospectively. Of
      210 duplex examinations, 139 were appropriate for morphological analysis of
      surface characteristics and echogenicity. RESULTS: Over half of the plaques
      examined had irregular surfaces (81, 58%) and displayed mixed (i.e.,
      heterogeneous) echogenic patterns (74, 53%). Irregular (68 of 81, 84%) and
      heterogeneous (65 of 74, 88%) plaques were associated with ipsilateral
      neurological symptoms (p < 0.0001). Similarly, 44 (54%) of 81 irregular plaques
      and 42 (57%) of 74 heterogeneous plaques were found in patients with cerebral
      infarctions in the carotid territory (p < 0.0001). CONCLUSIONS: Heterogeneous
      and/or irregular plaques were more often associated with both neurological
      symptoms and infarctions than smooth or homogeneous plaques. These findings may
      have implications in patient selection for endoluminal therapy.

PMID- 10088892
TI  - Duplex features of vein graft stenosis and the success of percutaneous
      transluminal angioplasty.
AB  - PURPOSE: To determine if criteria exist that are correlated to a successful
      outcome after balloon angioplasty for vein graft stenosis. METHODS: During a 5
      year period, duplex surveillance of 380 infrainguinal vein bypasses identified 76
      hemodynamically failing grafts (87 stenoses) requiring intervention. Percutaneous
      transluminal angioplasty (PTA) was selected over surgical repair based on 3
      criteria: time interval from primary grafting procedure, vein graft diameter, and
      stenosis length. The 28 (32%) stenoses (20 grafts) treated by PTA were used in a
      retrospective analysis to test if any variables favored a successful outcome.
      Patient and lesion characteristics, graft patency, and restenosis following PTA
      were correlated with duplex features of the stenosis recorded prior to,
      immediately after, and at 3- to 6-month intervals postprocedurally. RESULTS:
      Lesion characteristics that correlated with a successful outcome were vein size >
      or = 3.5 mm, lesion length < 2 cm, and appearance > 3 months after surgery.
      Conduit type, PTA site, patient demographics, and indication for bypass did not
      correlate with PTA durability. Nineteen lesions in 13 grafts met these criteria
      (group 1), while 9 stenoses in 7 grafts did not (group 2). Lesion severity based
      on duplex velocity measurements were similar in both groups before (p = 0.40) and
      after (p = 0.32) treatment. During the mean 21-month follow-up, group 1 grafts
      required less intervention (p = 0.035). At last follow-up, hemodynamic changes
      were durable in group 1 (p = 0.0068) but not in group 2 (p = 0.39). CONCLUSIONS:
      Selection of vein graft stenoses for treatment by PTA can be based on temporal
      and duplex data. PTA of short (< 2 cm) stenoses in good caliber veins (> or = 3.5
      mm) appearing > 3 months after bypass placement was durable with a late
      intervention rate of approximately 10%. Direct surgical repair or replacement is
      recommended for early (< 3 months) and/or long segment stenoses that develop in
      small caliber conduits.

PMID- 10088894
TI  - Re: Femoral artery exposure for endovascular aneurysm repair through oblique
      incisions.

PMID- 10088895
TI  - Introduction: what is where in the medial temporal lobe?

PMID- 10088896
TI  - Medial temporal lobe activations in fMRI and PET studies of episodic encoding and
      retrieval.
AB  - Early neuroimaging studies often failed to obtain evidence of medial temporal
      lobe (MTL) activation during episodic encoding or retrieval, but a growing number
      of studies using functional magnetic resonance imaging (fMRI) and positron
      emission tomography (PET) have provided such evidence. We review data from fMRI
      studies that converge on the conclusion that posterior MTL is associated with
      episodic encoding; too few fMRI studies of retrieval have reported MTL
      activations to allow firm conclusions about their exact locations. We then turn
      to a recent meta-analysis of PET studies (Lepage et al., Hippocampus 1998;8:313
      322) that appears to contradict the fMRI encoding data. Based on their analysis
      of the rostrocaudal distribution of activations reported during episodic encoding
      or retrieval, Lepage et al. (1998) concluded that anterior MTL is strongly
      associated with episodic encoding, whereas posterior MTL is strongly associated
      with episodic retrieval. After considering the evidence reviewed by Lepage et al.
      (1998) along with additional studies, we conclude that PET studies of encoding
      reveal both anterior and posterior MTL activations. These observations indicate
      that the contradiction between fMRI and PET studies of encoding was more apparent
      than real. However, PET studies have reported anterior MTL encoding activations
      more frequently than have fMRI studies. We consider possible sources of these
      differences.

PMID- 10088897
TI  - Encoding and retrieval in human medial temporal lobes: an empirical investigation
      using functional magnetic resonance imaging (fMRI).
AB  - The precise functional role of the hippocampus in human episodic memory is an
      unresolved question though it has recently been suggested that distinct medial
      temporal lobe (MTL) regions are involved in encoding and retrieval operations
      respectively. For example, a recent meta-analysis of positron emission tomography
      (PET) literature has suggested a rostral-caudal functional division in the medial
      temporal lobes (MTL), with rostral MTL mediating encoding and caudal MTL
      retrieval operations. However, a review of the combined PET and fMRI literature,
      reported in the present issue, while noting systematic discrepancies between PET
      and fMRI, reaches a conclusion that posterior MTL is involved in encoding. Here
      we present fMRI data, from a modified artificial grammar learning paradigm, that
      examines two questions concerning the functional role of the hippocampus, and
      related MTL structures in episodic memory. Firstly, we test a hypothesis that
      anterior hippocampus is activated during encoding and that this response is
      greater for novel items. Secondly, we test whether increasing familiarity with
      stimulus material is associated with a posterior MTL neural response. Our
      empirical findings support both hypotheses in that we demonstrate a left anterior
      hippocampal response sensitive to encoding demands and a posterior
      parahippocampal response sensitive to retrieval demands. Furthermore, we show
      that both anterior and posterior hippocampal responses are modulated to the
      degree to which stimuli can be assimilated into a meaningful rule-based
      framework.

PMID- 10088898
TI  - Level of sustained entorhinal activity at study correlates with subsequent cued
      recall performance: a functional magnetic resonance imaging study with high
      acquisition rate.
AB  - Functional magnetic resonance imaging (fMRI) with high acquisition rate was
      performed during the intentional memorizing of words to specify which medial
      temporal lobe structure is important in determining what words are subsequently
      remembered in a cued-recall test and to characterize the time course of
      activation in that structure. Functional images of six healthy young subjects
      were analyzed by two subject- and voxel-wise statistics: First, to identify brain
      areas transiently engaged in encoding of words, brain activity during memorizing
      visually presented words and watching a fixation cross was compared by a
      Kolmogorov-Smirnov statistic (KS-test). Second, to identify brain areas whose
      activity correlates with memory encoding success, a Kendall's correlation was
      calculated between signal intensity at study and performance in a subsequent cued
      recall test. Averaged signal intensities were plotted as a function of time to
      depict the time course of brain activity detected by both statistical tests. The
      level of slowly modulated, sustained activity in Brodmann area 28 (entorhinal
      cortex) did not respond transiently as study words appeared, but did correlate
      positively with subsequent test performance. More left than right activity in
      Brodmann area 45 (dorso-lateral prefrontal cortex) and bilateral activity in
      Brodmann area 44 (premotor cortex) exhibited transient hemodynamic responses that
      did not show any relation to subsequent memory performance. Thus, the study
      identified a novel pattern of slowly modulated brain activity in human entorhinal
      cortex that may represent a declarative memory encoding state whose level
      predicts whether experiences will be remembered or forgotten.

PMID- 10088899
TI  - Bridging the gap: integrating cellular and functional magnetic resonance imaging
      studies of the hippocampus.
AB  - The importance of the medial temporal lobe in memory has been studied extensively
      at the neuronal, neural ensemble, and systems level. In this report, we discuss
      recent systems level neuroimaging results in relation to neurophysiological
      studies of the hippocampus and related structures within the medial temporal
      lobe. By combining our knowledge across the cellular and systems levels we sought
      to gain theoretical insight and a better understanding of the function of the
      hippocampus and related medial temporal lobe structures. The integration of
      information from studies carried out at the cellular and neural ensemble level
      with studies at the systems level is difficult because of the vast differences in
      spatial and temporal resolution of the different research methodologies,
      differences in neuroanatomy across species, and differences in the types of
      behavioral and cognitive paradigms used in rat, nonhuman primate, and human
      studies. Despite these methodological and species-related differences, the
      neurophysiological studies offer insight into many of the questions raised by
      recent neuroimaging studies. For instance, there is physiological evidence that
      suggests that the hippocampal memory system is functionally heterogeneous, which
      may explain some of the discrepancies in the location and extent of activation
      reported by different imaging studies of the medial temporal lobe. In addition,
      we describe recent computational models of the hippocampus which may be useful
      for bridging the gap between neurophysiological and neuroimaging data.

PMID- 10088900
TI  - Differential modulation of a common memory retrieval network revealed by positron
      emission tomography.
AB  - Functional neuroimaging is uniquely placed to examine the dynamic nature of
      normal human memory, the distributed brain networks that support it, and how they
      are modulated. Memory has traditionally been classified into context-specific
      memories personally experienced ("episodic memory") and impersonal non-context
      specific memories ("semantic memory"). However, we suggest that another useful
      distinction is whether events are personally relevant or not. Typically the
      factors of personal relevance and temporal context are confounded, and it is as
      yet not clear the precise influence of either on how memories are stored or
      retrieved. Here we focus on the retrieval of real-world memories unconfounding
      personal relevance and temporal context during positron emission tomography (PET)
      scanning. Memories differed along two dimensions: They were personally relevant
      (or not) and had temporal specificity (or not). Recollection of each of the
      resultant four memory subtypes-autobiographical events, public events,
      autobiographical facts, and general knowledge-was associated with activation of a
      common network of brain regions. Within this system, however, enhanced activity
      was observed for retrieval of personally relevant, time-specific memories in left
      hippocampus, medial prefrontal cortex, and left temporal pole. Bilateral
      temporoparietal junctions were activated preferentially for personal memories,
      regardless of time specificity. Finally, left parahippocampal gyrus, left
      anterolateral temporal cortex, and posterior cingulate cortex were involved in
      memory retrieval irrespective of person or time. Our findings suggest that
      specializations in memory retrieval result from associations between subsets of
      regions within a common network. We believe that these findings throw new light
      on an old debate surrounding episodic and declarative theories of memory and the
      precise involvement of the hippocampus.

PMID- 10088901
TI  - Automatic activation of the medial temporal lobe during encoding: lateralized
      influences of meaning and novelty.
AB  - In contrast to early failures, recent functional brain imaging studies have shown
      that medial temporal lobe (MTL) structures are active during performance of a
      variety of tasks. These studies have revealed three properties of the MTL that
      are consistent with its critical role in establishing new declarative memories.
      First, the MTL is automatically engaged whenever an event is experienced, with
      the side of activation (left, right) dependent on the nature of the material
      presented (verbal, nonverbal). Second, the strength or amount of activity depends
      on how well the material is encoded. Deep encoding will produce more MTL activity
      than shallow encoding. Depth of encoding-related increases in activity are more
      commonly seen on the left, because deep encoding is nearly always synonymous with
      encoding for meaning, and, therefore, depends on left-lateralized language
      mechanisms. Third, the amount of MTL activity depends on novelty. Unfamiliar
      events and contexts will produce more MTL activity than familiar events and
      contexts. Novelty-related increases are more commonly seen on the right, perhaps
      reflecting the greater role of the right hemisphere in maintaining tonic
      attention and arousal. These findings suggest a hemispheric division of labor
      involving encoding for meaning (left) and novelty detection (right), both of
      which lead to better remembering.

PMID- 10088902
TI  - Positron emission tomography correlations in and beyond medial temporal lobes.
AB  - This article discusses the potential usefulness of brain/ behavior correlational
      analyses in functional neuroimaging studies of memory, and how such analyses can
      illuminate the role of medial temporal lobes (MTL) and the hippocampus in
      episodic and declarative memory processes such as encoding and retrieval.
      Reanalysis of the results of four previously reported positron emission
      tomography (PET) studies yielded evidence of both positive and negative between
      subjects correlations between recognition-memory accuracy and regional blood
      flow. The sites of these correlations were in MTL regions as well as in other
      cortical and subcortical areas, including frontal lobes (Brodmann areas 6, 9, 10,
      11, and 47), temporal lobes (BAs 21, 22, and 38), insula, fusiform gyrus, and
      cuneus/precuneus. These findings were discussed with respect to issues such as
      localization of the correlation sites, the distinction between brain sites
      revealed by brain/cognition correlational analyses ("how" sites) and those
      yielded by cognitive subtraction methods ("what" sites), the tendency of the
      "how" sites in MTL to occur in the left hemisphere, the tendency of other "how"
      sites to occur in one or the other hemisphere, rather than bilaterally, and the
      meaning and "reality" of both brain/behavior correlations and task-related
      activations. Because of the known incidence of false-positives, all neuroimaging
      data, including those involving the localization of "what" and "how" memory sites
      in MTL and other brain regions, need to be interpreted cautiously, and findings
      of individual studies should not be overinterpreted.

PMID- 10088903
TI  - Hippocampal system and declarative (relational) memory: summarizing the data from
      functional neuroimaging studies.
AB  - In the last several years there have been impressive strides in the ability to
      explore the nature of hippocampal system functioning in humans by employing
      functional neuroimaging methods, permitting such methods to be used in
      conjunction with neuropsychological methods to better understand the role of the
      hippocampal system in memory. In this paper, we review the literature on
      functional imaging studies of the hippocampal system, summarizing the data and
      testing these data against a number of theories or explanatory accounts of
      hippocampal function. We consider five alternative explanatory accounts of, or
      ideas about, hippocampal function- some from already existing work, for which the
      functional imaging data can provide a new test, and others that have emerged
      directly from the functional imaging work, and that have yet to be tested for
      their fit of data from neuropsychological methods. We conclude that the
      relational (declarative) memory account, in which it is proposed that the
      hippocampal system plays a critical role in binding together multiple inputs to
      permit representations of the relations among the constituent elements of scenes
      or events, can better accommodate the full range of imaging (and other existing)
      data than any other explanatory account of hippocampal function.

PMID- 10088904
TI  - First rotavirus vaccine licensed: is there really a need?
AB  - The first rotavirus vaccine was licensed in the United States on 31 August 1998
      for the prevention of severe rotavirus diarrhea in children. Despite this
      landmark in new vaccines, many pediatricians and public health professionals in
      Europe are uncertain of the need for this vaccine for the routine immunization of
      infants. In Europe, ample evidence suggests that rotavirus is the most common
      cause of hospitalizations for severe diarrhea among children, but proper studies
      documenting the disease burden of rotavirus or the cost-effectiveness of a
      rotavirus immunization program have only been conducted in the United Kingdom
      following epidemiologic models used in the United States. All children are
      infected with rotavirus during their first few years of life, 30-50% of diarrheal
      hospitalizations among children <5 years are due to this agent, and, by the age
      of 5 years, between 1 in 40 and 1 in 77 children in Europe and the United States
      may be hospitalized for rotavirus. The first vaccine is a live, oral preparation
      combining four different serotypes of rotavirus and administered in three doses
      with other childhood immunizations. The good efficacy against severe rotavirus
      diarrhea, the low risk of adverse side effects and the positive cost
      effectiveness equation have led the two major immunization advisory groups in the
      U.S. to recommend this vaccine for routine use in American infants. European
      physicians and policy-makers should re-examine the epidemiology and disease
      burden of rotavirus diarrhea now that an effective method of prevention is at
      hand.

PMID- 10088905
TI  - Rotavirus vaccine studies in Europe.
AB  - Following the discovery and recognition of rotavirus as an important human
      enteropathogen, work towards the development of rotavirus vaccines was begun in
      the USA and Europe. The first candidate rotavirus vaccine was launched by
      SmithKline-RIT, Belgium, and studied in clinical trials in Finland, Yugoslavia,
      Italy, Switzerland, Austria and the UK. Efficacy trials in Finland of RIT 4237
      strain live oral bovine rotavirus vaccine resulted in some fundamental findings
      about rotavirus immunity in humans: protection against disease rather than
      infection; better protection against severe than mild disease and heterotypic
      rather than homotypic protection. Another bovine rotavirus vaccine, strain WC-3,
      was studied briefly in France. Also studies of rhesus rotavirus vaccine were
      started early in Europe, and efficacy studies were carried out in Finland and
      Sweden. Recently, rhesus-human re-assortant tetravalent (RRV-TV) rotavirus
      vaccine was tested in a field trial in Finland this study was pivotal for the
      registration of the vaccine in the USA and European Union countries. Despite
      extensive experience with rotavirus vaccines in Europe, the need for such
      vaccines in many European countries still requires further assessment.

PMID- 10088906
TI  - Seasonality and diversity of Group A rotaviruses in Europe.
AB  - Group A rotaviruses are a major cause of severe gastroenteritis in children under
      4 y of age worldwide. Group A rotaviruses have been identified in many animal and
      bird species, they are antigenically complex, and multiple serotypes infect
      humans. Re-assortant rotavirus vaccines are now available which confer protection
      against severe illness due to rotavirus serotypes G1-4. Before vaccines are
      introduced it is necessary to establish the diversity of rotavirus in the target
      population to ensure efficacy and to establish a baseline for future surveillance
      strategies. The purpose of this review is to describe our current knowledge of
      the diversity of rotaviruses across Europe. Since multinational studies with
      standardized methodology have not been performed, this review is based on the
      available published studies. In Europe, more than 90% of Group A rotavirus
      strains that have been typed are of serotypes G1-4, with an average 8% of non-G1
      4 strains in published studies. The percentage of non-typeable strains may
      fluctuate from one year to another, and has been as high as 18% in one study in
      Great Britain, indicating the need for a more systematic study. Group A rotavirus
      infection typically occurs as a winter peak in the European countries studied.
      Comparison of seasonality data from national laboratory surveillance systems
      showed seasonal differences, with the annual rotavirus peak occurring first in
      Spain, usually in December, followed by France in February, and ending in
      Northern Europe in England and Wales in February or March, and the Netherlands
      and Finland in March.

PMID- 10088907
TI  - Incidence and estimates of the disease burden of rotavirus in Sweden.
AB  - Laboratory and hospitalization data from two children's hospitals with large
      primary catchment areas and national laboratory and hospitalization data for
      children under 4 y of age with acute diarrhoea were compiled to estimate the
      number of hospitalizations and the cost burden associated with rotavirus
      diarrhoea in Sweden. According to our estimates 1500-1700 rotavirus-associated
      hospitalizations occur annually in Sweden in children under 4 y of age (3.7
      hospitalizations/1000 children/y). This number represents 2.3% of admissions for
      all diagnoses in children of this age group. The cost of these hospitalizations
      is 13.5-15 million Swedish crowns (US$1.8-2 million). Serotyping by PCR for two
      years revealed that serotype 1 (G1) was the most common (49% and 58%,
      respectively) identified. Serotypes 2-4 were identified in the following
      proportions G2 (23% and 5%), G3 (21% and 0%) and G4 (7% and 16%). The national
      laboratory report data for 1993-96 show that as much as 7-13% of rotavirus
      infections occur in elderly people.

PMID- 10088908
TI  - Rotavirus gastroenteritis in Finland: burden of disease and epidemiological
      features.
AB  - The burden of disease attributable to childhood rotavirus infection in Finland
      was assessed from data on hospital admissions for acute gastroenteritis and from
      reported virological diagnoses of rotavirus from 1985 to 1995. The mean number of
      hospitalizations (3584 annually in children under 5 y of age) corresponded to
      approximately 5.6% of the birth cohort. Rotavirus was estimated to be responsible
      for 54% of cases; accordingly, 3% of all children in Finland are hospitalized for
      rotavirus diarrhoea. The monthly distribution of hospitalizations for acute
      diarrhoea showed a similar pattern as monthly diagnoses of rotavirus, with a long
      epidemic period starting as early as November or December and lasting until June
      or even July. The prevalent rotavirus G-type throughout the study period was G1,
      which was detected in over 60% of the cases; however, in the season 1988-89 G4
      was the prominent type. Improved case management has led to a shorter duration of
      hospital stay (3.3 d in 1985 vs. 2.3 d in 1995), but otherwise these was no
      significant trend for rotavirus gastroenteritis over the years. These findings
      underscore the need to control rotavirus gastroenteritis with a specific
      intervention, notably rotavirus vaccination.

PMID- 10088909
TI  - Epidemiology of rotavirus infections in The Netherlands.
AB  - This paper reviews published and unpublished data from epidemiological and
      virological studies of rotavirus in the Netherlands to identify gaps in our
      knowledge; it includes analysis of surveillance data for seasonality and age
      groups at risk. Rotavirus was found in approximately 5% of stool specimens from
      people consulting a physician for gastroenteritis. Of these cases, 38% were under
      5 y of age. A clear seasonality was observed, with a peak in rotavirus activity
      in winter and early spring. In one hospital-based study between 1976 and 1983,
      rotavirus was found in 30% of children under 3 y of age hospitalized for
      gastroenteritis. In addition, nosocomial infections have been documented.
      Analysis of monthly data from laboratory surveillance from 1981 to 1996 showed
      that between 6 and 16% of stool samples tested positive for rotavirus, again with
      a clear seasonal distribution. A total of 98% of rotavirus strains that were
      typed were G-type 1-4. We conclude that more recent data about hospitalization
      rates are needed for a well-founded cost-benefit analysis.

PMID- 10088910
TI  - An estimate of the proportion of diarrhoeal disease episodes seen by general
      practitioners attributable to rotavirus in children under 5 y of age in England
      and Wales.
AB  - Mean weekly incidence rates for a 4-week period of new episodes of infectious
      intestinal disease (IID) and laboratory reports of faecal isolations in children
      under 5 y of age presenting in general practice were used to estimate the
      incidence of IID due to rotavirus infection in England and Wales. Between January
      1992 and December 1996, a total of 92452 new episodes of IID were seen at
      sentinel general practices and reported to the Royal College of General
      Practitioners (RCGP) Research Unit in Birmingham, UK. Of these 32% (29592) were
      in children under 5 y of age. During the same period the Communicable Disease
      Surveillance Centre (CDSC) in London, UK received 159532 reports of faecal
      identifications in children under 5 y of age; 69219 (43%) of these were due to
      rotavirus. By modelling RCGP data and laboratory reports, the proportion of
      episodes attributable to rotavirus infection was estimated to be 29% (95% CI: 24%
      to 34%). By extrapolation of RCGP data it was estimated that rotavirus accounted
      for 762000 of new episodes of IID nationally in children under 5 y of age between
      January 1992 and December 1996. Implementation of a rotavirus vaccination
      programme could substantially reduce the incidence of childhood diarrhoea.

PMID- 10088911
TI  - Diarrhoea-related morbidity and rotavirus infection in France.
AB  - To assess the importance of diarrhoea in France and, specifically, rotavirus
      related diarrhoea among children, we reviewed data obtained from three
      complementary sources: (1) general practitioner (GP) sentinel surveillance; (2)
      hospital discharge data from paediatric hospitals; and (3) laboratory based
      surveillance. The GP sentinel network is based on 500 physicians who
      electronically notify new cases of eight illnesses, including diarrhoea, each
      week. It was estimated that about 3.3 million patients seek medical attention for
      diarrhoea from their GP each year, with a winter outbreak associated with an
      increased rate of isolation of rotavirus. A national system of hospital discharge
      diagnosis was used to estimate the burden of diarrhoeal morbidity in two
      paediatric wards in Tours, France. Between 1994 and 1996, 1164 patients under 15
      y of age (9.7% of all admissions) were admitted for diarrhoea, of whom 83% were
      reported as having viral gastroenteritis; 14.3% were dehydrated and 52% were
      under 1y old. Hospital admissions had a seasonal pattern similar to notifications
      from sentinel GP for children under 5 y old. A centralized laboratory
      surveillance network representing 17 of the 22 French regions describes a
      rotavirus outbreak each winter that is concomitant of outbreaks detected by the
      GP sentinel network and seen in hospitals. Most of the isolates (98%) identified
      through this surveillance system are among children under 5y of age. All the data
      reviewed in this study indicate that the epidemiology of rotavirus diarrhoea in
      France fits well with what has been reported in other developed countries.

PMID- 10088912
TI  - Occurrence and impact of community-acquired and nosocomial rotavirus infections-
      a hospital-based study over 10 y.
AB  - The need for a rotavirus vaccine in any particular country depends primarily on
      the number of hospitalized cases. Since only limited data are available for
      Germany, we undertook a retrospective hospital-based analysis in order to gather
      further information. From 1987 through 1996, a total of 3618 inpatients were
      hospitalized with a diagnosis of gastroenteritis (ICD 9). In 892 (25%) of them
      the causative organism was a rotavirus. During the same period, 1886 (out of
      8383; 22%) stool specimens tested in the hospital laboratory were obtained from
      rotavirus-positive inpatients. In 49.2% the infection was community-acquired, and
      in the remainder of nosocomial origin. Infants under 4 months of age (n = 709:
      38%) predominated among both the nosocomial and community-acquired infections.
      Premature neonates made up 26% of the nosocomial, but only 2% of the community
      acquired cases of diarrhoea. The winter peak (January) was most pronounced in the
      age group 4-12 months, but in those more than 1 y old the peak came a month
      later. The median hospitalization time for community-acquired cases was 4 d (mean
      5.9 d). The mortality was 0.1%. Rotavirus infection must therefore be regarded as
      a considerable burden, particularly with regard to infants and young children.
      Furthermore, the morbidity due to nosocomial infection with the rotavirus,
      analysed here in a long-term observational study, is unexpectedly high.

PMID- 10088913
TI  - Epidemiology and impact of rotavirus diarrhoea in Poland.
AB  - Hospital and laboratory data were analysed in three hospitals to estimate
      rotavirus disease burden in 1994-96. Community acquired gastroenteritis was
      diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of
      196 children had rotavirus nosocomial infections (39% of all rotavirus community
      acquired and nosocomial cases). Infants less than 24 months old and children less
      than 3 months old comprised 74% and 11.9% of admissions for rotavirus,
      respectively. Almost 94% of children with rotavirus infection had severe
      gastroenteritis (score > or =11). The annual rate of rotavirus associated
      hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60
      months and 5.2/1000 infants under 24 months of age. The mean hospital stay was
      9.5 d (+/-9.8 d). We estimated that 8918 children under 60 months of age were
      hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899
      inpatient days. We conclude that rotavirus is a leading aetiological agent of
      severe gastroenteritis in young children in Poland and that the burden of this
      infection is significant. Rotavirus vaccine could significantly decrease the
      hospitalization rate and the financial impact of rotavirus gastroenteritis in
      Poland.

PMID- 10088914
TI  - Burden of human rotavirus-associated hospitalizations in three geographic regions
      of Hungary.
AB  - Data on hospital admissions and laboratory reports were used to estimate the
      number of hospitalizations of children aged 14 y or less in three geographic
      regions of Hungary due to group A rotavirus infection. Between January 1993 and
      December 1996, 9182 hospitalizations for gastroenteritis occurred, of which 1946
      (21%) were associated with rotavirus infection. Most (90%) of the rotavirus
      detections were among children aged 4 y or less. By extrapolation, an estimated
      5000 rotavirus-related hospitalizations (8.4/1000 children aged 4 y or less/y)
      occurred in Hungary during the study period. Marked seasonality of rotavirus
      infections was observed, with a peak of incidence from December to February.
      Rotaviruses with "long" RNA electropherotypes predominated each year, but in
      1995/1996 20% of electropherotypes in the Budapest area were "short". Effective
      surveillance is required for all children hospitalized for diarrhoea as part of a
      rotavirus immunization program in Hungary.

PMID- 10088915
TI  - Rotavirus infection among children with diarrhoea in Italy.
AB  - Despite the absence of a nationwide surveillance system for rotavirus infection,
      relevant information concerning the epidemiology of this pathogen in Italy can be
      obtained from hospital-based studies carried out since the early 1980s on
      patients with acute diarrhoea. A review of more than 50 papers and congress
      proceedings published in both international and national literature indicates
      that rotavirus is the most important cause of diarrhoea in Italy among young
      children requiring hospitalization, with a prevalence ranging from approximately
      20% to 40% in different studies. Infection is predominant among children aged 6
      24 months, although cases are also common in younger children and in children 2-3
      y of age. Despite differences among studies in geographical area, years and age
      group under investigation, an increase in rotavirus cases is consistently
      reported in the winter months, with a peak in February through April. Although a
      few studies have been conducted in non-hospitalized patients, rotavirus infection
      is significantly less frequent among outpatients with enteritis than among
      inpatients. Most circulating rotavirus strains typed from 1981 to 1992 belong to
      serotype 1 and, to a lesser extent, 4. However, untypable rotavirus strains have
      been found in these years, with prevalences up to 27%, suggesting a possible
      spread of non-serotype 1 through 4 strains.

PMID- 10088916
TI  - Impact of rotavirus disease in Spain: an estimate of hospital admissions due to
      rotavirus.
AB  - The epidemiology of rotavirus infection in Spain was investigated using
      information from existing surveillance systems. Reports from laboratories and
      data on hospital admissions were used to estimate the number of hospital
      admissions due to rotavirus infection. Between January 1989 and December 1995
      there were 8265 reports of rotavirus identification in the Sistema de Informacion
      Microbiologica, a voluntary national laboratory surveillance system. Where age
      was reported, 89.2% were in children under 5 y old. This represents 21.8% of all
      pathogens identified in faecal specimens in children of this age group. Between
      January and December 1994 there were 5639 admissions coded as "infectious
      intestinal disease" and 8225 as "non-infective gastroenteritis" in children under
      5 y of age in the Conjunto Minimo Basico de Datos, an obligatory hospital
      admissions surveillance system which covers 83% of public hospitals. Using
      regression analysis of admission data and laboratory reports it was estimated
      that rotavirus infection accounted for 3519 (25.3%) of the hospital admissions.
      We estimate that 4239 admissions attributable to rotavirus occurred in children
      under 5 y of age in Spain in 1994, a rate of 2.5/1000 population in this age
      group. These estimates are lower than those published for other countries, where
      the burden of disease is considered high enough to warrant a national vaccination
      programme. A cost-effectiveness study with Spanish information is essential
      before embarking on a national vaccination programme.

PMID- 10088917
TI  - Mandibular reconstruction in children using the vascularized fibula.
AB  - In this study, the authors review their experience with vascularized fibula
      transfers for mandibular reconstruction in children. They outline the indications
      for such reconstruction, their method of contouring the fibula to accurately
      resemble the resected mandible, reconstruction of the temporomandibular joint,
      and the use of vascularized muscle for the management of associated soft-tissue
      deficiencies. Ten consecutive patients, 5 to 17 years of age and undergoing this
      procedure, were assessed from a medical, dental, radiographic, and photographic
      standpoint. The fibulae were elevated via a lateral approach, osteotomized, as
      required, and fixation was achieved with titanium miniplates and screws. All
      transfers survived, with viability confirmed by early postoperative bone
      scanning. Five patients had temporomandibular joint reconstruction, and five
      patients required simultaneous reconstruction of soft-tissue defects with
      associated vascularized muscle. The postoperative follow-up ranged from 3 to 30
      months The occlusion of the remaining dentition, mandibular symmetry and
      projection, adequacy of lining and skin cover, and maximal mouth opening were
      reassessed. Occlusion was class 1 in all patients, and free-flap stability and
      function were in the normal range. However, soft-tissue contour was a problem.
      All wounds healed primarily without donor-site complications and with minimal
      recipient-site complications.

PMID- 10088918
TI  - Mandibular reconstruction with the free vascularized fibular flap: utility of
      three-dimensional computerized tomography.
AB  - Oncologic management in the mandibular area leaves important osseous defects,
      that require reconstructive procedures with vascularized osseous tissues.
      Mandibular reconstructions with free vascularized fibular flaps have well-defined
      indications and some advantages over various other types of vascularized osseous
      grafts, because the fibular graft permits the reconstruction of large mandibular
      defects. This study demonstrates the usefulness of three-dimensional (3D)
      tomography as a tool to determine the size of the defect, and with
      angiotomography, to define the anatomic pattern of the vascular pedicle. Five
      patients with varying mandibular tumors and osseous defects were evaluated with
      3D tomography in the pre- and postoperative periods. Two patients were
      immediately reconstructed with vascularized fibular flaps. 3D preoperative
      tomography showed the dimensions of the tumor, the dimensions of the mandibular
      resection, and the graft vascular pattern. Three patients were secondarily
      reconstructed, two of them with partial mandibular defects, and one patient with
      total mandibular reconstruction. In the preoperative period, 3D tomography was
      used to determine the dimensions of the mandibular defect, as well as the area of
      the osteotomies. The technology permits an exact knowledge of the dimension of
      mandibular defects, allowing better planning of reconstructive procedures.

PMID- 10088919
TI  - Functional assessment of the shoulder following latissimus dorsi muscle donation
      in the handicapped.
AB  - The latissimus dorsi muscle, one of the largest muscles in the human body, has
      gained widespread popularity in microsurgical reconstruction. Because the
      latissimus serves to adduct and medially rotate the upper extremity, caution in
      its use has been advocated in handicapped and non-ambulatory patients, although a
      paucity of information exists in the literature. The purpose of this reported
      project was to determine whether the loss of the latissimus dorsi could be
      documented objectively or subjectively, either in the preoperative condition or
      post-harvesting in the handicapped patients. Two paraplegic patients were
      studied. Results indicate a lack of objective functional deficit; this includes
      both the nerve-blocked state and the postoperative condition. In addition, both
      patients failed to demonstrate the need to change any activities of daily living.
      This evidence suggests that, although careful decisions must be made on a case-by
      case basis, the use of the latissimus dorsi muscle is not necessarily
      contraindicated in this group of patients.

PMID- 10088920
TI  - Microsurgical repair of Stensen's duct using an interposition vein graft.
AB  - Facial wounds are frequently associated with bone fractures and multiple trauma;
      however, disruption of the parotid gland or Stensen's duct is rare and is often
      associated with facial nerve palsy. Lesions are often undiagnosed on first
      assessment of the multiple trauma patient. If microsurgical repair of Stensen's
      duct provides good functional results, ignoring such lesions often leads to later
      complications such as fistulae and sialocoeles. Although simple ligation of
      Stensen's duct has been reported to give satisfactory results, the authors prefer
      a more anatomic reconstruction of this structure whenever possible. A case of
      Stensen's duct microsurgical repair using a vein graft are reported.

PMID- 10088921
TI  - Free adipofascial flap for scalp reconstruction: case report.
AB  - The authors describe a case in which a large defect of the scalp was present
      after tumor excision. It was covered with a free adipofascial flap and a split
      thickness skin graft, with satisfactory results. Numerous similar cases of scalp
      defects reconstructed with other free flaps have been described. But since donor
      site morbidity is minimized with free adipofascial flaps, they should be used
      more often for reconstruction of scalp defects.

PMID- 10088922
TI  - Salvage and reconstruction of complex post-extirpative knee wounds: a successful
      surgical protocol.
AB  - Six patients with massive post-extirpative wounds of the knee, all of whom had
      received adjuvant therapy, underwent wound closure and limb salvage via free
      tissue transfer in all but one case. No instance of delayed wound healing
      requiring surgery occurred among the patients reconstructed by microsurgical
      tissue transfer. Five of the six patients are presently ambulating on the
      salvaged extremity. A protocol for management of these complex wounds is
      presented.

PMID- 10088923
TI  - Transfer of flexor carpi ulnaris branch of the ulnar nerve to the pronator teres
      nerve: histomorphometric analysis.
AB  - Partial median-nerve injury high in the upper extremity, resulting from brachial
      plexus neuritis or trauma, can affect the pronator teres muscle and result in the
      inability to pronate the forearm. A nerve transfer from an ulnar nerve-innervated
      branch to the flexor carpi ulnaris (FCU) muscle to the branch to the pronator
      teres (PT) is an attractive option in this clinical scenario. This study, a
      histomorphometric analysis of nine cadaver specimens harvested at the proposed
      FCU branch to PT branch transfer site, demonstrates sufficient similarities
      between the two branches in total number of nerve fibers (371.6 with SEM 35.1,
      and 361.9 with SEM 47.1; p = 0.87) and nerve cross-sectional area (122,181
      microm2 with SEM 14,546 microm2, and 142,492 microm2 with SEM 19,633 microm2; p =
      0.42), to predict a functional transfer result. In addition, clinical application
      of this transfer resulted in functional pronation strength of M4+.

PMID- 10088924
TI  - Staging arteriovenous fistula loops for lengthening of free-flap pedicles.
AB  - The authors investigated the optimal period of maturation following the creation
      of arteriovenous (AV) loops using polyterafluoroethylene (PTFE) in a white rat
      model, which were subsequently used to support free-tissue transfer The AV loops
      in Group 1 (n = 17) were allowed to mature for 3 days prior to creation of the
      flap, while those from Group 2 (n = 14) were allowed to mature for 5 days.
      Results were compared to those from a previous study in which the authors
      reported an 80 percent initial patency rate (n = 30) and a 67 percent viability
      rate, based on 12 patent loops after 7 days. In the present study, patency rates
      were 59 percent for the 3-day group and 79 percent for the 5-day group; viability
      rates were 50 and 64 percent, respectively. Considering both patent and nonpatent
      loops, the overall viability rates were 29 and 50 percent respectively.
      Maturation periods longer than 3 days for AV loops constructed from PTFE
      micrografts were determined to be preferable for subsequent free-tissue transfer.

PMID- 10088925
TI  - Experimental vascular graft using small-caliber fascia-wrapped fibrocollagenous
      tube: short-term evaluation.
AB  - This study was undertaken to evaluate the application of autogenous fascia as a
      framework for a fibrocollagen tube for small-caliber vascular prostheses in
      Japanese white rabbits (n = 15). The fascia, measuring 10 x 40 mm, was harvested
      from the dorsal fascia and was carefully wrapped around a silicone rod of 1.5 mm
      in diameter. Then, the fascia-wrapped silicone rod was implanted into a
      subcutaneous pocket on the medial thigh. Four weeks later, the fascia-wrapped
      silicone rod was removed from the subcutaneous pocket. The rod was removed from
      the material, and the fascia-wrapped fibrocollagen tube was treated to make it
      antithrombogenic. Subsequently, the 1.5 x 10-mm fascia-wrapped tube was prepared
      as an arterial conduit. Using microvascular techniques, the tube was interposed
      into the divided femoral artery. Eleven of 15 grafts maintained patency over the
      follow-up period and no aneurysmal formation was found at any graft site.
      Microscopically, there was an ingrowth of endothelium with fibroblast
      proliferation from each end of the recipient vessel at 2 weeks after
      interposition; however, no neointima was found to line the center of the conduit.
      At 5 weeks after interposition, the neointimal growth rate was 70 percent. There
      was an ingrowth of endothelium with fibroblast proliferation from each end onto
      the entire internal surface of the conduit at 8 weeks after interposition.
      Further study is required before any long-term conclusions can be drawn.

PMID- 10088926
TI  - Determination of hindlimb transplantation-induced vascular albumin leakage and
      leukocyte activation during the acute phase of rejection.
AB  - Following transplantation, the microvascular endothelium and endothelial cells
      play a critical role in allograft rejection, as well as response to surgical
      trauma. In this study, endothelial-cell damage was assessed through microvascular
      permeability, and the role of surgical trauma was evaluated during the acute
      phase of limb allograft rejection. Eighteen isograft and 18 allograft composite
      tissue transplantations were performed between 72 rats. At 24-hr, 72-hr, and 7
      days follow-up, microvascular permeability, leukocyte activation, functional
      capillary perfusion, red-blood-cell velocity, vessel diameter, and an endothelial
      edema index were measured. The permeability index (PI) was statistically
      significantly greater in the allografts at all follow-up points, compared with
      the isograft controls (p <0.001). The number of rolling leukocytes was
      significantly greater in the allografts at 24 and 72 hr; the number of sticking
      and transmigrating leukocytes was greater at all three follow-up points; and the
      number of rolling lymphocytes was greater at 7 days (p <0.05). These findings
      demonstrate the increased rejection phenomenon in allografts, and the increased
      susceptibility to ischemia and reperfusion injury, compared with isograft
      transplants. Increased leukocyte activation and acute destruction of endothelial
      cell barrier function were demonstrated during the acute rejection period
      following composite limb allotransplantation.

PMID- 10088927
TI  - Rat walking tracks do not reflect maximal muscle force capacity.
AB  - The relationship between walking-track measurements and maximum force generation
      in reinnervated rat hindlimb muscles was assessed. A rat model was designed to
      result in a broad range of recoveries of both muscle force and walking-track
      measurements after unilateral sciatic nerve injury and reconstruction. Three
      months following sciatic nerve injury, maximal force in the extensor digitorum
      longus (EDL) muscle ranged from 1325 to 3666 mN, and maximal specific forces
      ranged from 137.5 to 359.4 kNm(-2). In the same animals, functional intermediate
      toe spread factor (FIS) ranged from -0.03 to -0.78. Neither the correlation
      coefficient between EDL muscle maximal force and FIS (r = 0.4) nor that between
      EDL maximal specific force and FIS (r = -0.2) were statistically significant. The
      lack of correlation between muscle maximal force values and walking-track
      measurements suggests that these neuromuscular tests are assessing different
      factors.

PMID- 10088928
TI  - Allergic bronchopulmonary aspergillosis and cystic fibrosis.

PMID- 10088929
TI  - Increased antigen-specific Th-2 response in allergic bronchopulmonary
      aspergillosis (ABPA) in patients with cystic fibrosis.
AB  - The majority of patients with cystic fibrosis (CF) become colonized with
      Aspergillus fumigatus (A. fumigatus) in the lower respiratory tract, the
      prevalence being up to 60%. Between 1-11% of CF patients develop allergic
      bronchopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected
      patients suffering from cystic fibrosis or atopic asthma have suggested a
      pathogenic role for antigen-specific "Th2-like" T lymphocytes. The aim of this
      study was to evaluate the quantitative importance of such Th2 cells, using
      improved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in
      unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF patients
      with ABPA and from a control group without ABPA. Thus, 20 patients with CF,
      heavily colonized with A. fumigatus in the lower respiratory tract, were studied:
      10 patients with ABPA, and 10 without. Unseparated PBMC were stimulated in vitro
      by A. fumigatus antigen and by an unrelated antigen (tetanus toxoid) as a
      control. After 6 days of stimulation, IL-4 and IL-5 (markers for Th2 cell
      activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were
      quantified in the supernatants by enzyme-linked immunosorbent assay. PBMC from
      ABPA patients secreted significantly higher amounts of IL-4, i.e., 0.48 (0.15
      0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/mL, compared to
      secretions obtained in non-ABPA CF controls of 0.07 (0.04-0.16) ng/mL and 3.00
      (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN-gamma secretion was
      similar in the two groups, amounting to 21.5 (2.05-72.5) ng/mL in ABPA patients
      vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant
      differences were obtained in the cytokine secretion induced by tetanus toxoid
      stimulation between the two groups. We conclude that ABPA in CF patients is
      associated with an antigen-specific, Th2-like T-cell immune response, as
      indicated by excessive secretion of IL-4 and IL-5.

PMID- 10088930
TI  - Bone mineral content and body composition in children and young adults with
      cystic fibrosis.
AB  - With dual energy X-ray absorptiometry (DEXA), it is possible to quantitate
      important aspects of growth in children with cystic fibrosis (CF), supplementing
      the usual measures of height and weight. Of particular concern during growth is
      the accumulation of bone mineral, since osteoporosis and fractures are well
      recognized problems in end-stage disease. Various measures of growth and body
      composition were examined in 40 children and young adults (ages 5.7-20.3 years,
      mean 11.9 years) and compared to age-, gender-, and race-matched normal controls.
      The mean (+/- SE) weight Z-score of the 40 CF patients was -0.70 +/- 0.11, and
      the mean height Z-score was -0.66 +/- 0.15. Relative to their matched normal
      controls, the CF patients had a deficit in total body bone mineral averaging
      19.1% +/- 3.0%. The deficits in total body bone mineral correlated with pulmonary
      and nutritional measures of disease severity. Serum vitamin D levels, calcium
      intake, age, gender, use of steroids, and CF genotype were not found to be
      significant factors. In this group of children and young adults with CF, height
      and weight measures of growth were not dramatically reduced (mean Z-scores = 
      0.7), yet large deficits in total body bone mineral averaging nearly 20% were
      identified.

PMID- 10088931
TI  - Prediction of early-onset asthma in genetically at-risk children.
AB  - The W.T. Grant Foundation Asthma Risk Study was designed to prospectively examine
      children who were considered at a genetically increased risk for the development
      of asthma. The respective contributions of 11 potential risk factors, both
      environmental and biological, were assessed in order to determine their relative
      roles in affecting the early onset of asthma. This is a report of an inception
      cohort of children born to asthmatic mothers and followed for a 3-year period.
      All 150 families were recruited from the general community and living within 2 h
      of the National Jewish Center for Immunology and Respiratory Medicine (Denver,
      CO). Mothers in the index risk sample had been previously diagnosed with asthma
      and were recruited during their pregnancy through physician referrals and media
      solicitation. The index sample of 150 families was 92% Caucasian and
      predominantly middle class. The mean age of mothers was 29.3 years, and of
      fathers, 31.1 years. The main outcome was the determination of the early onset of
      asthma and its association with quantified risk factors. By age 3 years, 14 of
      the 150 children had developed asthma. Frequent illness, IgE levels at age 6
      months, parenting difficulties, and early eczema were significantly associated
      with the onset of asthma (P = 0.003, P = 0.006, P = 0.01, and P = 0.03,
      respectively). Only frequent illness, elevated serum IgE levels, and parenting
      difficulties entered a predictive model where they were independently related to
      the development of asthma.

PMID- 10088932
TI  - Calcium-PS-dependent protein kinase C and surfactant protein A in isolated fetal
      rabbit type II alveolar cells and surfactant-related material.
AB  - The fetal lung secretes significant quantities of surfactant during late
      gestation to prepare for initiation of respiration at birth. However, the
      mechanism by which this occurs has not been determined. Since Ca2+
      phosphatidylserine (PS)-dependent protein kinase C has been implicated in
      surfactant secretion in adult lung, the present study was done to determine
      whether this enzyme is also involved in the initiation of surfactant release from
      fetal type II cells. Type II cells isolated from gestational day-24 fetal rabbits
      were used. Cells were prelabelled with [32P] and [3H]choline and exposed to 4beta
      phorbol ester (10(-5) M) for 2 h. Secretion product and subcellular fractions
      were isolated by removing the culture medium, mixing with homogenate from adult
      rabbit lung, and subfractionating by centrifugation on a sucrose gradient.
      Samples of secretion product were also prepared for electron microscopy. Ca2+-PS
      dependent protein kinase C was also assayed in some samples, and an add-back
      technique was used to determine whether enzyme activity in the intracellularly
      stored surfactant fraction was due to contamination. The results showed that
      material released by fetal type II cells after exposure to phorbol ester
      coprecipitated with adult rabbit lung lamellar bodies and microsomes.
      Morphologically, a range of forms, including lamellar-body-like structures, was
      detected. The released material originated largely from the lamellar body
      compartment of the fetal type II cells and displayed immunoreactivity with
      antibody to surfactant protein A (SP-A) at 35 and 70 kDa apparent molecular mass.
      Assay of protein kinase C in fetal type II cells showed that exposure to
      conditioned medium, which induces differentiation, increased activity. Incubation
      with phorbol ester induced translocation of activity to the microsomal fraction.
      Add-back assays suggested that protein kinase C activation by treatment with
      phorbol ester induced translocation of enzyme activity to the lamellar body
      fraction; none was detected prior to treatment. These results support a role for
      Ca2+-PS-dependent protein kinase C in initiation of surfactant release by
      interaction with the developing lamellar body compartment in fetal type II cells.

PMID- 10088933
TI  - Changes in pulmonary function in preterm infants recovering from RDS following
      early treatment with ambroxol: results of a randomized trial.
AB  - Several studies have demonstrated that ambroxol stimulates surfactant synthesis
      and has antioxidative and antiinflammatory effects. We investigated the effect of
      ambroxol on lung function in newborns with respiratory distress syndrome (RDS)
      weighing <1,500 g. In all, 102 newborns were enrolled (52 received ambroxol and
      50 placebo). After extubation, lung function tests were performed weekly using a
      face mask for ventilatory measurements and a catheter tip pressure transducer
      (diameter 1.7 mm) for esophageal pressure measurements (Pes) The flow-through
      technique was used to eliminate apparatus dead space and to allow long-term
      measurements during quiet sleep. Percentile curves of pulmonary function
      parameters from healthy newborns were used for comparison. During the first 28
      days, 42 newborns were extubated in the ambroxol group and 36 in the placebo
      group. The ventilatory parameters of both treatment groups were in the normal
      range and there were no significant differences between the two groups at any
      time. After extubation, the ratio of tidal volume to maximal esophageal pressure
      changes (V(T)/P(es,max)) was below the 10th percentile in the ambroxol and
      placebo-treated groups. In the ambroxol group the 10th percentile was reached on
      day 10, whereas in the placebo group the 10th percentile was reached
      significantly later (P < 0.05) on day 23. Modeling of power expenditures was used
      to identify the optimal breathing pattern so that small differences in
      ventilatory parameters between the two groups could be analyzed. We conclude that
      early ambroxol treatment has only a modest effect on lung function in newborns
      with established RDS. The sensitivity of tidal breathing parameters is not
      sufficient to detect these small changes in lung mechanics, but small
      improvements could be demonstrated in lung mechanics 10 days after extubation in
      the ambroxol-treated group.

PMID- 10088934
TI  - Predischarge monitoring of preterm infants.
AB  - The objectives of this study were: 1) to perform documented event-monitoring
      (DEM) for apnea (A, > or = 20 s) and bradycardia (B, < 80 beats per min for > or
      = 5 s) in premature infants prior to discharge, and 2) to examine the accuracy of
      nursing documentation (ND) of A and B. Forty-four stable preterm infants, with
      mean weights and gestational ages at birth (+/- SD) of 1,543 (+/- 365) g, and 30
      (+/- 2) weeks, respectively, were studied using DEM for 9 (+/- 2) days prior to
      discharge. Differences in DEM and ND were analyzed by the z-test for proportions.
      There were 561 true events recorded by DEM: 56 were As and 505 were Bs. ND
      revealed 296 events, 190 As and 106 Bs. Of the 56 true As on DEM, only 21 (38%)
      were correctly reported by ND (P < 0.001, 95% confidence interval (CI) 0.44
      0.81). Of the 505 true Bs on DEM, 153 (30%) were correctly reported by ND (P <
      0.001, CI 0.63-0.76). When ND was compared with DEM, 174 (59%) of NDs were true
      events. Of the 106 As on ND, only 21 (20%) were true As on DEM (P < 0.001, CI
      0.58-1). Of the 190 Bs on ND, 153 (80%) were true Bs on DEM (P < 0.001, CI 0.13
      0.26). ND did not detect 6 of the 33 infants who had significant events on DEM,
      while 4 of the 11 who had events reported on ND did not have any on DEM. Thus, 10
      infants were misclassified by ND (P < 0.01, CI 0.1-0.36). These results indicate
      that, compared to DEM, ND not only identified significantly fewer true As and Bs,
      but also misclassified a significant number of infants. We conclude that DEM
      performed prior to discharge for preterm infants at risk for apnea and
      bradycardia provides more objective and accurate information than ND.

PMID- 10088935
TI  - Bronchial challenge with carbachol in 3-6-year-old children: body plethysmography
      assessments.
AB  - Several studies of airway responsiveness in young children (3-6 years old) have
      been reported, but few have attempted measurements of airway resistance by body
      plethysmography. Therefore, we decided to study nonspecific bronchial
      responsiveness following cumulative doses of inhaled carbachol in 44 children
      with clinical asthma (CA group), 44 children with chronic cough (CC group), 38
      children with wheezy bronchitis in the first 2 years of life (WB group), and 40
      controls. Specific airway resistance (sRaw) was measured in a body
      plethysmograph, and specific airway conductance (sGaw=1/sRaw) was calculated. Two
      parameters were used to assess individual bronchial responses: 1) PD100 (the dose
      of carbachol which induced a 100% increase in sRaw), and 2) bronchial reactivity
      (BR), i.e., the slope of the log-dose sGaw response to carbachol. Significant
      differences were observed in PD100 and BR between the control group and the three
      groups of young patients (P < 0.001). Moreover, PD100 of the CA group was
      significantly lower than in the CC group (83.1 +/- 7.8 microg vs. 108.0 +/- 10.2
      microg, respectively, P < 0.05), but was similar to the WB group PD100 (94.4 +/-
      8.5 microg). BR in the CA group was significantly higher than in both the CC and
      WB groups (0.127 +/- 0.009 cm H2O-L.sec(-1) x log microg(-1) vs. 0.073 +/- 0.006
      cm H2O(-1) x sec(-1) x log microg(-1) and 0.082 +/- 0.006 cm H2O(-1) x sec(-1) x
      log microg(-1), respectively, P < 0.001). Repeatability and coefficients of
      variation were always acceptable. Continuous SaO2 monitoring in some children of
      the CA group demonstrated the safety of the method, which is proposed as a
      technique in future studies.

PMID- 10088936
TI  - Improved pulmonary distribution of recombinant human Cu/Zn superoxide dismutase,
      using a modified ultrasonic nebulizer.
AB  - Prophylactic, intratracheal instillation of recombinant human Cu/Zn superoxide
      dismutase (rhSOD) has been shown to lessen lung injury produced by 48 h of
      hyperoxia and mechanical ventilation in neonatal piglets. However, instillation
      of small volumes of rhSOD intratracheally would not be expected to result in
      uniform pulmonary distribution. Aerosolization is a technique that may improve
      pulmonary distribution of drugs, but is limited by the poor efficiency of most
      nebulizers. A newly modified ultrasonic nebulizer was tested to assess pulmonary
      distribution of rhSOD compared to that achieved by intratracheal instillation.
      rhSOD was dual-labeled with technetium-99m (99mTc) and a fluorescent analog
      (permitting quantitative and qualitative assessments of pulmonary distribution),
      and administered to neonatal piglets by intratracheal instillation or by
      aerosolization. Intratracheal instillation of rhSOD to piglets when supine
      resulted in nonuniform distribution, with most of the drug being found in the
      right caudal lobe, and localized in airways. Placing animals in 30 degrees of
      Trendelenburg and administering half the dose in the left and half in the right
      lateral decubitus positions improved distribution, but alveolar deposition
      remained patchy. Aerosolization using a modified ultrasonic nebulizer uniformly
      delivered 45.8 +/- 3.8% of the rhSOD to the lungs that had been placed in the
      nebulizer. The rhSOD was still active and present in airways and alveoli in a
      homogeneous fashion. We conclude that intratracheal instillation of rhSOD in
      small volumes results in nonuniform pulmonary distribution, while aerosolization
      enhances rhSOD distribution and alveolar deposition. This has important
      implications for ongoing clinical trials of rhSOD for the prevention of acute and
      chronic lung injury in premature neonates.

PMID- 10088937
TI  - Fatal invasive aspergillosis in an adolescent with cystic fibrosis.
AB  - We report on a 13-year-old girl with cystic fibrosis (CF) who developed
      refractory airflow obstruction despite high-dose steroids. She developed invasive
      aspergillosis and died despite oral and intravenous antifungal therapy. We
      speculate that the increasing use of immunosuppressive strategies and aggressive
      antipseudomonal therapy in CF may lead to an increase in aspergillus lung
      disease, including invasive aspergillosis in the future.

PMID- 10088938
TI  - Metastatic pulmonary calcification with ossification in a child with acute
      lymphoblastic leukemia.

PMID- 10088939
TI  - Progression from bronchopneumonia to inflammatory pseudotumor in a seven-year-old
      girl.

PMID- 10088940
TI  - High frequency of hysterectomies and appendectomies in fibromyalgia compared with
      rheumatoid arthritis: a pilot study.
AB  - We investigated, in retrospect, if there were differences in the frequency and
      types of abdominal surgery between newly diagnosed female fibromyalgia (n = 80)
      and rheumatoid arthritis (n = 47) patients performed before the formal diagnosis.
      There was no difference in the total number of abdominal operations between both
      groups. In the rheumatoid arthritis group more cholecystectomies (p = 0.01) were
      performed, probably due to the older age of these patients (58.5 vs 48.5 years).
      However, in the fibromyalgia group there were more hysterectomies (p = 0.04) and
      appendectomies (p = 0.05) than in the rheumatoid arthritis group.

PMID- 10088941
TI  - Oxaceprol is as effective as diclofenac in the therapy of osteoarthritis of the
      knee and hip.
AB  - In this multicentre (five centres in Germany), randomised, double-blind,
      comparative study, 150 patients with painful degenerative joint disease according
      to EULAR criteria received either oxaceprol (200 mg three times daily) or
      diclofenac (25 mg three times daily) for 20 days. Joint function, the primary
      variable, assessed according to Lequesne's indices, improved equally in both
      treatment groups to a clinically relevant degree. Joint mobility improved by
      approximately 60% in both groups. By the end of therapy in both groups, the
      period of pain-free walking time had more than doubled and subjectively evaluated
      pain perception (VAS) was reduced by almost 50% without any significant
      differences between the treatments. The incidence of adverse drug reactions was
      similar in both groups but oxaceprol induced milder symptoms. Oxaceprol is as
      effective and better tolerated than diclofenac in the treatment of
      osteoarthritis.

PMID- 10088942
TI  - On the prediction of Young's modulus in calcaneal cancellous bone by ultrasonic
      bulk and bar velocity measurements.
AB  - This study evaluated two different approaches to the prediction of Young's
      modulus (E) from ultrasonic velocity and density measurements in 23 cubes of
      cancellous bone from human calcaneae. The first approach used clinically
      applicable measurements of bulk velocity and bone mineral density (BMD), whilst
      the second involved bar velocity and apparent density, which are strictly in
      vitro measurements. Bulk velocities were measured with an immersion technique
      with 1 MHz transducers using three different transit time markers (first arrival,
      thresholding, zero-crossing). Bar velocities were measured in the defatted
      specimens using a contact technique with 37 kHz transducers in air. Volumetric
      BMD was derived from dual-energy X-ray absorptiometry measurements, and apparent
      density was measured directly. Compressive mechanical testing was used to
      determine E. Bulk velocity, bar velocity and E all displayed significant
      anisotropy, being greatest in the proximo-distal (PD) axis and least in the medio
      lateral (ML) axis. Bulk velocity was dependent on the transit time marker used,
      with velocity differences of up to 20% observed between different markers. Bar
      velocities were significantly lower than bulk velocities in all directions. Both
      bulk and bar velocities correlated with E (r2 = 0.26-0.83, r = 0.36-0.81,
      respectively) with stronger relationships obtained when the data for the three
      axes were pooled. The predictive ability of bulk velocities determined using
      different markers was similar. In general, combining velocity and density
      measurements yielded improved correlations with E. Thus, strong correlations were
      observed between E and the product of BMD and bulk velocity2 (r2 = 0.58-0.89),
      and the product of apparent density and bar velocity2 (r2 = 0.58-0.89). These
      results demonstrate that clinically applicable measurements of bulk velocity and
      BMD are good predictors of the elastic modulus of calcaneal bone, and that bulk
      and bar velocity, both alone and when combined with density measurements, have a
      similar predictive ability for mechanical properties.

PMID- 10088943
TI  - Serum IL-6, TNFalpha, p55 srTNFalpha, p75srTNFalpha, srIL-2alpha levels and
      disease activity in systemic lupus erythematosus.
AB  - The aim of this study was to determine whether the levels of serum cytokines IL-6
      and TNFalpha and of the soluble receptors p55 srTNFalpha, p75 srTNFalpha and srIL
      2ac are valuable markers of disease activity in patients with systemic lupus
      erythematosus (SLE) compared with the established parameters of anti-dsDNA, C3,
      C4 and CH50. Forty patients with SLE, 19 ambulatory and 21 hospitalised, were
      included in this study. On the day of blood sampling a clinical examination was
      performed and SLEDAI and ECLAM disease activity scores were used to assess
      disease activity. Nineteen patients had inactive disease and 21 patients had
      active disease. Thirteen patients from the second group developed nephritis. In
      these patients the blood sampling and disease activity assessment were performed
      twice (at presentation and 6 months after treatment). Serum levels of cytokines
      and soluble receptors were measured by ELISA. Serum levels of cytokines and
      soluble receptors of patients with active disease were significantly higher than
      in patients with inactive disease (IL-6 p = 0.0004, TNFalpha p = 0.0015, srIL-2c
      p<0.0001, p55 srTNFalpha p<0.0001, p75 srTNFalpha p<0.0001). Serum soluble
      receptor levels of patients with inactive disease were higher than those of
      healthy controls (p55 srTNFalpha p<0.0001, p75 srTNFalpha p = 0.0002, srIL-2alpha
      p = 0.0012). No significant difference was found for TNFalpha and IL-6 (TNFalpha
      p=0.015, IL-6 p=0.019). Serum TNFalpha levels and especially srIL-2alpha, p55
      srTNFalpha( and p75 srTNFalpha levels correlated strongly with SLEDAI and ECLAM
      disease activity scores, anti-dsDNA, C3, C4 and CH50 (p<0.0001). Serum soluble
      receptor (srIL-2alphac, p55 srTNFa, p75 srTNFalpha) levels were higher in
      patients with nephritis before treatment and decreased significantly 6 months
      after treatment (p=0.005). The same trend was noticed with SLEDAI and ECLAM
      disease activity scores (p = 0.005) and anti-dsDNA (p = 0.008). In contrast, no
      significant differences were observed for C3 and C4 levels before and after
      treatment, which suggests that soluble receptors of cytokines are more sensitive
      markers of disease activity than C3 or C4 in predicting improvement. Serum levels
      of srIL-2alpha, p55 srTNFalpha and p75 srTNFalpha could provide useful
      information about disease activity in SLE patients, especially in cases where the
      other markers do not.

PMID- 10088944
TI  - Optimisation of HLA-B27 testing by association of flow cytometry and DNA typing.
AB  - HLA-B27 typing contributes to the diagnosis of ankylosing spondylitis. The
      classical technique of microlymphocytotoxicity is costly and can give false
      negative results. We have compared 304 samples using two relatively new methods -
      flow cytometry and PCR-SSP - and evaluated their respective uses in routine
      analysis. Flow cytometric HLA-B27 testing was performed using three monoclonal
      anti-B27 antibodies (HLA-ABC-m3, GS145.2 and FD705 clones). Cut-off values were
      established to differentiate HLA-B27-positive from HLA-B27-negative samples with
      ROC curves. Although flow cytometric analysis with a reliable monoclonal antibody
      (mAb) is valuable for HLA screening, none of the HLA-B27 flow cytometry protocols
      was sufficient on its own to ascertain the HLA phenotype in 100% of samples. Two
      false negatives were observed with the FD705 mAb and the use of two different
      monoclonal antibodies did not increase the accuracy of HLA-B27 typing. HLA-B27
      typing using molecular biology is a reliable but costly technique. Therefore we
      suggest that DNA typing could be used as a complementary technique and applied to
      samples whose HLA-B27 phenotype cannot be determined by flow cytometry. The
      association of flow cytometry and DNA typing is, in our experience, an economical
      and reliable approach.

PMID- 10088945
TI  - Circulating P- and L-selectin and T-lymphocyte activation and patients with
      autoimmune rheumatic diseases.
AB  - Circulating levels of P- and L-selectins and the degree of T-lymphocyte
      activation were assessed by enzyme-linked immunosorbent assays in 75 selected
      patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic
      lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood
      donors matched for age and gender. Mean levels of P-selectin were significantly
      higher than normal in RA (lower in patients with clinical remission) and SSc
      (higher in patients with early-onset diffuse disease), but not in SLE. In
      contrast, mean L-selectin levels were significantly higher than normal in SLE (no
      correlation to the degree of disease activity), but not in RA or SSc. Mean levels
      of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte
      activation, in patients with active RA, SSc and SLE were almost double the normal
      level; however, correlations between individual levels of circulating P- or L
      selectins and sIL-2R within groups revealed a strong positive correlation only
      between L-selectin and sIL-2R (r = 0.66, p<0.001), and only in patients with SLE.
      Given the different expression of P- and L-selectins, these findings indicate a
      distinct pattern of immune cell activation in chronic diseases that share an
      overactivation of T-lymphocytes. The possible clinical value of quantitation of
      circulating P-selectin in patients with RA and SSc on the one hand, and L
      selectin in patients with SLE on the other, should be investigated by prospective
      studies.

PMID- 10088946
TI  - The use of two different Health Assessment Questionnaires in Turkish rheumatoid
      arthritis population and assessment of the associations with disability.
AB  - The aim of this study was to compare and evaluate the Health Assessment
      Questionnaire (HAQ) and Arthritis Impact Measurement Scale (AIMS) in our patient
      population with rheumatoid arthritis (RA) and also to find some associations with
      clinical assessment of disability. One hundred and twenty-three consecutive adult
      patients with RA were included in the study. Pain, and global assessments by
      patients and physicians were recorded using a 10 cm visual analogue scale. Each
      patient completed the HAQ and AIMS questionnaires. Correlations among tender and
      swollen joint counts, erythrocyte sedimentation rate, pain, and AIMS anxiety and
      depression scores were all investigated. Pearson correlation was used to assess
      the possible correlations between each questionnaire and clinical variables. Pain
      and the AIMS subscales of mobility, dexterity, social activity and activities of
      daily living correlated with global assessments by patients and physicians, and
      tender joint counts. Depression correlated with pain and disability (HAQ). It was
      also of note that we observed high intercorrelation between the global
      assessments of physicians and patients. It was concluded that a measure of
      functional status, patient global assessment and pain score should be considered
      as important in the evaluation of RA patients. Measuring psychological well-being
      also provides further information. The HAQ, with the addition of the anxiety and
      depression sections of AIMS (CLINHAQ), provides the advantage of a global
      evaluation of these chronically ill patients.

PMID- 10088947
TI  - Endothelial tissue factor induction by T lymphocytes in systemic sclerosis.
AB  - We evaluated the ability of circulating T lymphocytes obtained from patients with
      systemic sclerosis (SSc) to induce the expression of tissue factor (TF) by human
      umbilical vein endothelial cells (HUVECs), and compared the results with those
      obtained from healthy controls. Nine patients with SSc and 10 sex- and age
      matched healthy subjects were studied. Peripheral T lymphocytes obtained from SSc
      patients induced TF activity from HUVECs in a dose-dependent manner. A
      significant induction of endothelial TF was observed when 2 x 10(6) lymphocytes
      per well (TF values, mean+/-SD: 0.34+0.21U/microg of cell protein vs 0.04+/-0.03;
      n = 9, p = 0.001) or 1 x 10(6) lymphocytes per well (0.13+/-0.06 vs 0.04+/-0.04;
      n = 8, p<0.001) were added to HUVEC cultures. Lower concentrations of T
      lymphocytes were ineffective. Similar results were obtained with control
      lymphocytes. There were no differences in endothelial TF induction between
      patients and controls at any lymphocyte concentration tested. Within the SSc
      group, there were no correlations between TF activity and clinical features or
      disease duration.

PMID- 10088948
TI  - Beta thalassaemia: a report of 20 children.
AB  - Beta-thalassaemias have a wide variety of musculoskeletal system manifestations.
      In this cross-sectional study, we aimed to investigate the frequency and features
      of musculoskeletal system problems in children with beta-thalassaemia. A total of
      20 beta thalassaemic patients with an average age of 13.8 years were enrolled in
      the study. In all patients studied, detailed history regarding musculoskeletal
      involvement was taken and locomotor examinations were performed. All patients
      underwent radiographic examination with standing anteroposterior and lateral X
      rays of the spine. Two physicians blinded for the diagnosis used Cobb technique
      for determining the degree of scoliosis. In 12 of 20 patients (60%) locomotor
      system involvement was found. Most frequent complaints were arthralgia and low
      back pain in 30% and 25% of patients respectively. Scoliosis was detected
      radiologically in 40% of patients with a lateral curve of at least 5 degrees
      Cobb.

PMID- 10088949
TI  - Vanishing pulmonary hypertension in mixed connective tissue disease.
AB  - A 29-year-old woman with mixed connective tissue disease presented with signs of
      progressive pulmonary hypertension. After admission to the hospital her condition
      worsened rapidly and she developed a cardiac arrest resistant to cardiopulmonary
      resuscitation. Therefore, emergency extracorporeal assist was performed. No
      pulmonary embolism was found. Right heart catheterisation showed severe pulmonary
      hypertension, which was treated with nitric oxide ventilation. She was weaned
      from the extracorporeal assist with high doses of inotropic agents. Because of
      suspicion of exacerbation of her underlying disease, which led to pulmonary
      hypertension, immunosuppressive treatment was started with high doses of
      corticosteroids and plasma exchange. This resulted in slow recovery over the next
      four weeks. Control echocardiography showed complete normalisation of cardiac
      function without signs of pulmonary hypertension. Two months after admission she
      was discharged from the hospital in good condition.

PMID- 10088950
TI  - Type I osteogenesis imperfecta: diagnostic difficulties.
AB  - A 65-year-old woman presented with vertebral fractures of the lumbar spine and a
      history of pathological fractures following minor trauma, which had occurred
      before the onset of menopause. Her past medical history was significant for
      intermittent low back pain since childhood, which was attributed to thoracolumbar
      scoliosis. A diagnosis of unclassifiable osteoporosis was made until invasive
      diagnostic procedures suggested a mild form of type I osteogenesis imperfecta
      (OI). In unclear or atypical perimenopausal osteoporosis and diagnosis of OI
      should be considered.

PMID- 10088951
TI  - Paraspinal abscess following facet joint injection.
AB  - Injection to the zygapophysial joint is a procedure which is performed frequently
      for diagnostic or therapeutic reasons in the management of back pain. It is
      generally considered to be free of significant complications. We report a patient
      who developed a paraspinal abscess following a lumbar facet joint injection.

PMID- 10088952
TI  - Gout and secondary amyloid.
AB  - A case of gout and secondary amyloid is described. This rare association is
      described and the literature is reviewed.

PMID- 10088953
TI  - Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus,
      secondary antiphospholipid syndrome and IgM monoclonal paraproteinaemia.
AB  - In this case report, a woman is described who developed systemic lupus
      erythematosus at the age of 36 years affecting the central nervous system and
      kidneys, showing the serological evidence of an acquired C1 inhibitor deficiency,
      but also developing an antiphospholipid syndrome and IgM lambda type
      paraproteinemia. During the 25 years follow-up she did not show any signs of
      angioedema. Although the immunological abnormalities are still constantly
      present, the disease has been quiescent since the past three years. The possible
      pathophysiology of clinical and laboratory features are discussed.

PMID- 10088954
TI  - A case of Buerger's disease associated with high levels of lipoprotein(a).

PMID- 10088955
TI  - Superior and inferior limb ischaemia in giant cell arteritis: angiography follow
      up.
AB  - Giant cell arteritis most often affects the superficial temporal artery. Arterial
      territories such as the facial, carotid, myometrial and upper and lower limb
      arteries may be affected. In this paper we describe the case of a 52-year-old
      patient with upper and lower limb ischaemia who presented with grade III
      ischaemia in the left lower limb. Giant cell arteritis was diagnosed as
      responsible for the symptoms. After treatment with corticoids, an angiographic
      improvement was evidence after 2-year period. The low number of reported cases,
      the diverse symptoms and varied course make diagnosis of GCA difficult.
      Therefore, GCA must be taken into consideration in the ischaemia of inferior and
      superior limbs whether isolated or simultaneous.

PMID- 10088956
TI  - Systemic adverse effect of antithyroid drugs.
AB  - Antithyroid drugs adverse effects are varied and rare. Autoimmune disorders
      (vasculitis, lupus erythematosus, polyarthritis...) are unusual and serious
      complications of antithyroid drugs. Since 1945, fewer than 100 cases of systemic
      manifestations related to antithyroid drugs have been reported in the literature,
      most frequently with propylthiouracil. The outcome is usually good after drug
      discontinuation, but some fatal cases have been reported. Because possible cross
      sensitivity with other antithyroid drugs, the appropriate treatment for
      hyperthyroidism relapse if a patient has had an antithyroid drug adverse
      reaction, should be 131I-Iodine or surgery. We report four new cases of systemic
      manifestations during propylthiouracil therapy.

PMID- 10088957
TI  - Adult onset of multifocal eosinophilic granuloma of bone: a long-term follow-up
      with evaluation of various treatment options and spontaneous healing.
AB  - We report a case of multifocal-monosystemic Langerhans cell histiocytosis (LCH),
      formerly usually referred to as eosinophilic granuloma (EG) of bone. The
      condition developed in a 36-year-old man. A notable infrequent thoracic spine
      location and two successive distinct costal lesions were observed. Both the first
      costal site and the vertebral location healed spontaneously; the second costal
      lesion underwent biopsy resection. The patient's disease course with an 8-year
      follow-up is discussed with reference to various treatment options, emphasising
      in selected cases a watchful conservative approach, in view of the widely
      documented potential for spontaneous healing.

PMID- 10088958
TI  - Polyarthritis as a complication of intravesical bacillus Calmette-Guerin
      immunotherapy for bladder cancer.
AB  - Bacillus Calmette-Guerin (BCG) is the most effective agent currently available
      for the treatment of superficial bladder cancer. However, this form of treatment
      is associated with some complications, including arthritis. In this report, we
      present a 69-year-old woman who developed inflammatory polyarthritis following
      BCG treatment for superficial bladder cancer. The arthritis resolved following
      treatment with a non-steroidal anti-inflammatory drug and chloroquinine.

PMID- 10088959
TI  - Successful treatment of rapidly progressive lupus nephritis associated with anti
      MPO antibodies by intravenous immunoglobulins.
AB  - We report a case of systemic lupus erythematosus (SLE) associated with crescentic
      glomerulonephritis and myeloperoxidase-specific anti-neutrophil cytoplasmic
      antibodies (MPO-ANCA). A 34-year-old Japanese female patient diagnosed with SLE
      developed rapidly progressive renal failure and nephrotic syndrome. Haemodialysis
      was required to restore renal function. Methylprednisolone pulse therapy followed
      by plasmapheresis did not suppress the progression of renal failure, so she was
      treated with high-dose intravenous immunoglobulin (IV-IG) therapy, which was well
      tolerated and effectively prevented renal failure. A renal biopsy showed diffuse
      proliferative lupus nephritis (WHO classification IVc) with predominant crescent
      formation and scant subendothelial immune deposits. These findings indicate that,
      in addition to lupus nephritis, which usually results from the deposition of
      circulating or locally formed immune complexes, MPO-ANCA may be involved in the
      pathogenesis of crescentic glomerulonephritis. Furthermore, we propose that IV-IG
      is an effective therapy for MPO-ANCA-related renal crisis in lupus nephritis.

PMID- 10088960
TI  - Unilateral distal extremity swelling with pitting oedema in giant cell arteritis.
AB  - We describe a case of an 82-year-old woman with giant cell arteritis, who
      developed unilateral pitting oedema of the dorsum of the right hand, foot and
      distal part of the right forearm as well as tenosynovitis of the right wrist
      extensors, mild synovitis of the right wrist, metacarpophalangeal and
      metatarsophalangeal joints, during relapse of giant cell arteritis. Increase of
      corticosteroids resolved the giant cell arteritis, pitting oedema and
      tenosynovitis.

PMID- 10088961
TI  - Myocarditis of mixed connective tissue disease: favourable outcome after
      intravenous pulsed cyclophosphamide.
AB  - A 30-year-old woman with mixed connective tissue disease was admitted with
      Wernicke's aphasia and progressive dyspnoea with chest pain. Multiple brain
      infarcts on a computed tomographic scan were compatible with a thromboembolic
      aetiology. Echocardiography showed marked hypokinesia of the posterior wall,
      biventricular dilatation and a decreased left-ventricle ejection fraction (40%).
      A diagnosis of myocarditis was made on myocardial biopsies disclosing
      interstitial lymphocytic infiltrates and myocardial fibre necrosis. A treatment
      with steroids and monthly pulsed cyclophosphamide was introduced. The heart
      function rapidly improved as assessed by a left-ventricle ejection fraction of
      55% and remained stable 17 months thereafter.

PMID- 10088962
TI  - Fatal polyarteritis nodosa with massive mesenteric necrosis in a child.
AB  - Polyarteritis nodosa (PAN) is a rare vasculitic syndrome in childhood. There are
      few reported cases of ischaemic necrosis of the intestine and even fewer
      survivors in adults. We report the case of a 10-year-old boy with PAN and an
      acute abdomen that required operative intervention. Evidence was found of
      mesenteric arteritis with large ischaemic segments resulting in infarction and
      perforation.

PMID- 10088963
TI  - Early intervention for children with cerebral visual impairment: preliminary
      results.
AB  - According to the ophthalmological literature, cerebral visual impairment (CVI) is
      defined as a temporary or permanent visual loss caused by a disturbance of the
      posterior visual pathways and/or occipital lobes. The study of CVI is still a new
      field, and diagnosis is frequently difficult and sometimes may not even be
      considered. Different studies have taken into account various aetiologies of CVI.
      Neurological problems are common findings in children with CVI and this
      population may also show ocular abnormalities. The present study reviews the
      clinical history of 76 patients who have been examined at the Robert Hollman
      Foundation, Cannero, Italy, over the past 3 years. Infants and children were
      studied from birth to 4 years of age from both a neurological and an
      ophthalmological point of view. Taking the development of the children into
      account, responses to visual stimulation were analysed in order to compare the
      behaviours exhibited by the sample with those described in literature.

PMID- 10088964
TI  - The relationship between the effect of setting a goal on standing broad jump
      performance and behaviour regulation ability in children with intellectual
      disability.
AB  - The objectives of the present study were to investigate the differences in
      standing broad jump performance between two task conditions (with and without
      goal) and to clarify the relation of verbal behaviour regulation to this
      difference in children with intellectual disability. The subjects were 30
      children with intellectual disability with an average age of 16.2 years. In the
      without-goal condition, subjects were instructed to jump as far as possible. In
      the with-goal condition, on the other hand, subjects were given a goal set 20 cm
      away from the distance of the first trial in the without-goal condition and
      instructed to jump for the goal. Verbal behaviour regulation ability was measured
      by three tasks on Garfield's motor impersistence test keeping eyes closed,
      protruding tongue with eyes open and keeping mouth open. The mean performance of
      the with-goal condition was 108 cm, while that of the without-goal condition was
      102 cm. The difference between these results was significant, thus indicating the
      effectiveness of setting a goal to improve jumping performance. Among three
      independent variables (chronological age, IQ and behaviour regulation score),
      only the behaviour regulation score was found to be significantly related to the
      condition difference. It was more effective to demonstrate the goal when the
      behaviour regulation abilities of the children were lower, but giving the
      children a goal was not effective for subjects with Down's syndrome. Children
      with Down's syndrome were considered to have a deficiency in the motor ability
      itself, not in the system for expressing the motor ability.

PMID- 10088965
TI  - Supporting individuals with intellectual disability and challenging behaviour in
      integrated work settings: an overview and a model for service provision.
AB  - An overview of supported employment and its historical context is examined, and
      supported employment for individuals with both intellectual disability and
      challenging behaviour is discussed. A proposed model for working with such
      individuals is briefly outlined. This model is based on previous work in the
      field, and is characterized by a multi-component approach which addresses the
      issues of both support and behavioural intervention.

PMID- 10088966
TI  - Economic impact of feeding a phenylalanine-restricted diet to adults with
      previously untreated phenylketonuria.
AB  - The aim of the present study was to estimate the direct healthcare cost of
      managing adults with previously untreated phenylketonuria (PKU) for one year
      before any dietary restrictions and for the first year after a phenylalanine-
      (PHE-) restricted diet was introduced. The resource use and corresponding costs
      were estimated from medical records and interviews with health care professionals
      experienced in caring for adults with previously untreated PKU. The mean annual
      cost of caring for a client being fed an unrestricted diet was estimated to be 83
      996 pound silver. In the first year after introducing a PHE-restricted diet, the
      mean annual cost was reduced by 20 647 pound silver to 63 348 pound silver as a
      result of a reduction in nursing time, hospitalizations, outpatient clinic visits
      and medications. However, the economic benefit of the diet depended on whether
      the clients were previously high or low users of nursing care. Nursing time was
      the key cost-driver, accounting for 79% of the cost of managing high users and
      31% of the management cost for low users. In contrast, the acquisition cost of a
      PHE-restricted diet accounted for up to 6% of the cost for managing high users
      and 15% of the management cost for low users. Sensitivity analyses showed that
      introducing a PHE-restricted diet reduces the annual cost of care, provided that
      annual nursing time was reduced by more than 8% or more than 5% of clients
      respond to the diet. The clients showed fewer negative behaviours when being fed
      a PHE-restricted diet, which may account for the observed reduction in nursing
      time needed to care for these clients. In conclusion, feeding a PHE-restricted
      diet to adults with previously untreated PKU leads to economic benefits to the
      UK's National Health Service and society in general.

PMID- 10088967
TI  - Characteristics of older adults with intellectual disabilities referred for
      crisis intervention.
AB  - The aim of the present study was to identify the age correlates of behavioural
      crises in adults with intellectual disability (ID) living in the community. The
      cohort consisted of 185 clients (IQ < 70), ranging in age from 20 to > 70 years,
      who were referred to a crisis intervention programme specializing in services to
      individuals with dual diagnosis over a 7-year period. A retrospective cross
      sectional analysis of historical and contemporaneous variables was completed.
      Referrals for crisis intervention were not related to the age of the client
      Aggression and non-compliant behaviour occurred with similar frequency in all age
      groups. Other behaviours, including withdrawal, self-injury, stereotypy and
      symptoms of psychiatric disorders, occurred less often in older clients. Severity
      of ID affected the pattern of behavioural crises that resulted in referral. The
      results suggest that people with ID residing in community settings still
      experience behavioural crises as they grow older. Confirmation of the trends
      reported in the present study might signal a need for accelerating the
      development of comprehensive age-span community mental health and behavioural
      supports.

PMID- 10088968
TI  - Diagnosis of fragile-X syndrome: the experiences of parents.
AB  - In order to assess some aspects of the quality of care for families seeking the
      cause of their child(ren)s intellectual disability, a postal questionnaire was
      sent to parents of children with fragile-X syndrome, who were members of the UK
      Fragile-X Society. Although the interval taken to get a diagnosis ('lagtime') has
      fallen over time, other aspects of care could still be improved. Most families
      feel that having a diagnosis is an advantage, but many still find the diagnostic
      process distressing and feel unsupported. Not all families are referred for
      genetic counselling, and even those who are do not always understand or retain
      the information given. Most families feel that having a diagnosis is a benefit
      rather than a disadvantage.

PMID- 10088969
TI  - The relationship between psychiatric and physical health in elderly people with
      intellectual disability.
AB  - Elderly people with intellectual disability have high rates of both psychiatric
      and physical disorders. In the elderly general population, these disorders are
      known to be associated. Whether such an association exists amongst elderly people
      with intellectual disability is unclear, but the resolution of this question is
      of clinical as well as academic importance. Psychiatric and physical assessments
      were completed on 134 people with intellectual disability aged 65 years and over
      (93.7% of the ascertained population living in Leicestershire, UK). The
      relationship between the two disorders was statistically examined. The number of
      physical disorders, age, level of intellectual disability and smoking status were
      retained in the logistic regression equation which predicted caseness for
      dementia in 79.9%. Similar statistical modelling for psychiatric disorders (other
      than dementia) retained the level of intellectual disability as the only
      explanatory variable in the equation. These results differ from the elderly
      general population, but are in keeping with the one previous intellectual
      disability study. In view of the poor use of general medical services by elderly
      people with intellectual disability, knowledge of such comorbidity should alert
      psychiatrists to the need for physical assessments in order to optimize health.

PMID- 10088970
TI  - Evaluation of a computer-aided system providing pictorial task instructions and
      prompts to people with severe intellectual disability.
AB  - The present study extended the evaluation of a computer-aided system providing
      pictorial instructions and prompts to promote task performance in people with
      severe intellectual disability. Four people were presented with two sets of
      tasks. The participants used the computer-aided system for one set and a card
      (control) system for the other. The results indicate that the computer-aided
      system was more effective than the card system with all participants. Three of
      the participants preferred the computer-aided system, while one favoured the card
      system.

PMID- 10088971
TI  - The early fluidic and optical physics of cytometry.
AB  - All forms of cytometry, depend on the basic laws of physics, including those of
      fluidics, optics, and electronics, most of which were established centuries ago.
      Flow cytometry depends critically on the fluidics presenting each individual cell
      with precision to the sensing volume. This is intersected by a high-intensity
      light source, and light scattering and fluorescence from suitably stained
      constituents in each cell are captured by the light-collecting optics and
      measured. The works and observations of Bernoulli and Euler in the 18th century,
      Reynolds in the 19th century, and Crosland-Taylor in the 20th century in the
      field of fluid dynamics laid the foundations for hydrodynamic focussing, which is
      the primary prerequisite for presenting individual cells to the sensing volume.
      In addition, electrostatic cell sorters must have the ability to generate stable
      droplet formation in the jet-stream issuing from the flow chamber nozzle. The
      origins here can be traced to work carried out in the early to mid-19th century
      by Savart, Magnus, and Thomson. Flow, image, and confocal cytometry are all
      dependent on the laws of optics, including those of reflection and refraction as
      well as numerous other optical principles. The observations and works of
      Socrates, Ptolemy, Snel, and Descartes between about BC 370 and 1637 were of
      seminal importance in developing the laws of reflection and refraction. In the
      mid-17th century Hooke illustrated the power of magnifying glasses and microscopy
      in his Micrographia and Newton was responsible for explaining colours in the
      spectrum. Huygens, toward the end of the 17th century, put forward the concept of
      point source light propagation contributing to a wave front. Finally, Thomas
      Young, early in the 19th century, established the wave form of light from
      interference patterns. Most people will be familiar with some of these
      discoveries and the investigators who carried out the work; some people will be
      familiar with all of these. However, very few people are likely to have had the
      opportunity and privilege to access the very early works and the original data
      and manuscripts, or translations thereof, which laid the foundations of physics
      that enabled our discipline to be established. It is always important for any
      discipline to remember its roots and to appreciate the seed from which those
      roots grew, for it is much easier to learn and fully understand when we have a
      knowledge of the source and the logical progressions that lead from one discovery
      to the next. This knowledge lends perspective to our current endeavours as the
      past, after all, created the present, which in turn contributes to the future. In
      this article, which was presented as an invited lecture at the 9th Canadian
      Consensus meeting on AIDS, I have attempted to trace the origins of the early
      work on the physics of fluidics and optics, which laid the foundations.

PMID- 10088972
TI  - Hyperdiploidy and apparent aneusomy in mesothelial cells from non-malignant
      effusions as detected by fluorescence in situ hybridization (FISH).
AB  - Interphase cytogenetics by fluorescence in situ hybridization (FISH) can be used
      to detect malignant cells characterized by chromosomal aneuploidy. However,
      apparent aneusomy in normal "control" tissues has to be considered when using
      FISH as diagnostic tool. In effusions as model tissue exposed to metastasis, the
      definition of cut-off levels for background aneusomy by FISH was aimed in this
      study. Using centromeric probes representing chromosomes 7, 8, 11, 12, 17 and 18,
      extensive chromosome copy number enumeration by single-color FISH analysis was
      performed in pleural and ascitic effusions derived from 15 patients with various,
      non-malignant diseases. In all effusions, cells with gain of hybridization
      signals for several or all chromosomes tested were found (in up to 1.94% of
      cells). A consistent finding was high grade hyperdiploidy (>4 centromeric
      signals). Mesothelial elements mainly contributed to hyperdiploidy in effusions,
      as demonstrated by a combined analysis of FISH and immunocytochemistry with
      staining for cytokeratin. Dual-color FISH analysis showed that hyperdiploidy was
      predominantly corresponding to polyploidization; however, there were always minor
      cell populations classified as aneuploid by dual-color FISH. In conclusion,
      stringent criteria have to be applied to distinguish malignancy-related
      aneuploidy from background aneusomy by FISH.

PMID- 10088973
TI  - Correlation of rhodamine 123 efflux by neoplastic plasma cells with clinical and
      biological characteristics of multiple myeloma.
AB  - Although a variable proportion of multiple myeloma patients can achieve response
      with conventional chemotherapy, residual tumor cells, which are refractory,
      finally reemerge leading to disease progression. The expression of the multidrug
      resistance protein (MDR1) has been one of the most extensively explored
      mechanisms of drug resistance and has been related to a poor response to
      chemotherapy in several human tumors. Nevertheless, a careful analysis of the
      literature on MDR1 expression in multiple myeloma (MM) shows the existence of
      disturbing discrepancies as regards both the incidence of MDR1 over-expression
      and its clinical value. A prerequisite for the assessment of MDR1 in tumor cells
      should be the identification of the neoplastic cells present in the sample. This
      is particularly important in MM, where the percentage of tumor cells in bone
      marrow (BM) is relatively low. In the present study we have analyzed the
      functional expression of MDR1 in BM plasma cells (PC), from a group of 40
      untreated MM patients. For that purpose, the rhodamine 123 efflux assay was used
      in combination with specific staining for plasma cells (CD38 strong+). The mean
      fluorescence channel (MFC) of rhodamine 123 in myelomatous PC from MM patients
      was 311 and 110 after incubating cells with this fluorochrome for 15 and 60 min,
      respectively. The median percentage of rhodamine 123 elimination by BM PC was of
      61% (range: 0.29 to 88%). Upon analyzing the relationship between the ability of
      myelomatous PC to eliminate rhodamine 123 and other clinical and biological
      disease characteristics we found that, within the group of patients displaying
      high MDR1 expression (>61% rhodamine efflux), there was a higher incidence of
      cases with bone disease (P = 0.014) and advanced clinical stages (P = 0.031),
      greater calcium (P = 0.007) and creatinine serum levels (P = 0.061), and lower
      levels of albumin in serum (P = 0.015). All these parameters are usually
      associated with a poor prognosis. When we analyzed the possible relationship
      between the ability of BM PC to eliminate rhodamine 123 and the presence of
      numerical chromosome abnormalities we observed that a low MDR1 expression was
      related to a higher incidence of trisomies of chromosomes 6 and 17, although
      these differences did not reach statistical significance (P = 0.06). In spite of
      these associations, from the prognostic point of view, MDR1 expression did not
      correlate with other relevant prognostic factors, response to treatment (P =
      0.38) or overall survival (P = 0.12).

PMID- 10088974
TI  - Rapid in vitro biocompatibility assay of endovascular stents by flow cytometry
      using platelet activation and platelet-leukocyte aggregation.
AB  - Clinical studies suggest that stent design and surface texture are responsible
      for differences in biocompatibility of metallic endovascular stents. A simple in
      vitro experimental setup was established to test stent-induced degree of platelet
      and leukocyte activation and platelet-leukocyte aggregation by flow cytometry.
      Heparin-coated tantalum stents and gold-coated and uncoated stainless steel
      stents were tested. Stents were implanted into silicone tubes and exposed to
      blood from healthy volunteers. Platelet and leukocyte activation and percentage
      of leukocyte-platelet aggregates were determined in a whole-blood assay by
      subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and
      fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric
      analysis. Blood taken directly after venous puncture or exposed to the silicone
      tube alone was used as negative controls. Positive control was in vitro
      stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of
      platelet activation and significant increase in monocyte- and neutrophil-platelet
      aggregation were observed in blood exposed to stents (P < 0.05). In addition,
      leukocyte activation was induced as measured by increased CD45 and CD14
      expression. Heparin coated stents continuously induced less platelet activation
      and leukocyte-platelet aggregation than uncoated stainless steel stents of the
      same length and shorter stents of the same structure. Stent surface coating and
      texture plays a role in platelet and leukocyte activation and leukocyte-platelet
      aggregation. Using this simple in vitro assay and whole blood and flow cytometry,
      it seems possible to differentiate stents by their potency to activate platelets
      and/or leukocytes. This assay could be applied for improving the biocompatibility
      of coronary stents.

PMID- 10088975
TI  - Analyte specific reagents: FDA final rule and implications for your clinical flow
      cytometry laboratory.
AB  - In summary, the FDA Final Rule on Analyte Specific Reagents has provided clarity
      and simplification for manufactures to develop and market products. The burden of
      establishing performance characteristics is now the responsibility of the
      clinical flow cytometry laboratory. The FDA now requires a disclaimer to be
      included in every lab report utilizing these products.

PMID- 10088976
TI  - Mean fluorescence intensity of dual stained cells.

PMID- 10088977
TI  - Chronic pelvic pain: the assessment as therapy.

PMID- 10088978
TI  - Differences in behavior profile between normotensive subjects and patients with
      white-coat and sustained hypertension.
AB  - It has been hypothesized that white-coat hypertensives (WCHs) have lower
      cardiovascular risk than sustained hypertensives (HTs), but higher emotional
      reactivity. We evaluated 92 HT patients (clinic and daytime BP>140/90 mmHg), 52
      WCHs (clinic BP>140190 and ambulatory daytime BP<134/ 85 mmHg), and 74
      normotensive subjects (NTs, clinic BP<140/90 and ambulatory daytime BP<134/85
      mmHg), aged between 24 and 72 years, and matched for educational level, age,
      gender, and weight for depression, psychopathology, well-being, and quality of
      life. HTs showed worse scores than WCHs and NTs on most of the psychological
      variables; no differences were found between WCHs and NTs except on physical
      mobility. Daytime BP variability was HTs>WCHs>NTs, whereas nighttime BP
      variability was HTs>WCHs=NTs. We conclude that HTs have worse psychological
      profiles than the other two groups. WCHs and NTs have similar psychological
      profiles, although WCHs have a higher daytime BP variability, which is not
      associated with higher emotional reactivity.

PMID- 10088979
TI  - Bone mineral density and depression: a community study in women.
AB  - In a community sample of 102 Portuguese white women we evaluated the relationship
      between osteoporosis and indexes of psychopathology and well-being. Depressive
      symptoms were assessed by the Beck Depression Inventory (BDI), psychopathology by
      the Hopkins Symptom Checklist-90 Revised (SCL-90-R), and quality of life using
      the Psychological General Well-Being Index. A questionnaire comprising social,
      demographic, clinical, and behavioral characteristics was also used. The sample
      prevalence of osteoporosis was 47.1%. Women with osteoporosis presented
      significantly higher scores on the total BDI (16+/-9 vs. 13+/-10, p=0.045) and
      lower scores in the hostility (0.8+/-0.6 vs. 1.2+/-0.7, p=0.012) and phobic
      anxiety (1.1+/-0.8 vs. 1.5+/-0.9, p=0.041) subscales of the SCL-90-R. No
      differences were found regarding mean general well-being scores (62+/-17 vs. 64+/
      19, p=0.665). This study showed that women with osteoporosis have significantly
      higher levels of depressive symptoms and a corresponding higher prevalence of
      depression, independent of other factors strongly associated with osteoporosis,
      such as age or body mass index.

PMID- 10088980
TI  - PTSD in ambulant RTA victims: a randomized controlled trial of debriefing.
AB  - This report examines initial distress levels, course of symptoms, incidence of
      posttraumatic stress disorder (PTSD), predictors of short-term outcome, and value
      of prophylactic counseling in a consecutive series of 40 ambulant trauma clinic
      attenders with minor road traffic accident (RTA) injuries. Subjects were randomly
      allocated to intervention and monitoring groups following assessment at a mean of
      7 days posttrauma and reassessed at 3 months using a variety of standard rating
      scales. Seventy-five percent reported significant levels of distress at 1 week
      posttrauma. By 3 months this had decreased sharply to 35%, and 22% were
      significantly impaired by clinical assessment. Incidence of PTSD over 3 months
      was estimated at 19% and point prevalence at 3 months posttrauma was 9%. High
      initial distress, increasing age, and high levels of perceived threat were
      significant independent predictors of morbidity, and no significant differences
      in outcome were found between intervention and monitoring groups at 3 months.

PMID- 10088981
TI  - Health anxiety and characteristics of self-initiated general practitioner
      consultations.
AB  - Health anxiety has been hypothesized to lead to a cycle of repeated medical
      consultations. We investigated the relationship of health anxiety to patients'
      frequency of general practitioner visits, and to their expectations about the
      index visit in 200 general practice attenders. Health anxiety scores declined
      modestly with age, and were similar in men and women. Frequency of visits rose
      from 2.6 per year in the lowest decile of health anxiety to 4.2 in the highest
      (p=0.033). Across the same range, the odds of seeking advice prior to visiting
      the doctor rose from 0.25 to 0.56 (p=0.034), and the odds of believing that a
      specialist referral would be needed rose from 0.22 to 0.48 (p =0.008). There was
      no association between health anxiety and previous referral for investigation of
      symptoms that had not resulted in a medical diagnosis, nor with attitudes to
      prescriptions, possibly because there was little variation in either. In this
      population, absolute levels of health anxiety were low. Nevertheless, within this
      "normal" range, there was an association between level of health anxiety and
      frequency of visiting, and with expectations for the index visit. The findings
      support the health anxiety model as predicting use of services by psychologically
      normal persons.

PMID- 10088982
TI  - Increased serum mitogenic activity for arterial smooth muscle cells associated
      with relaxation and low educational level in human subjects with high but not low
      hostility traits: implications for atherogenesis.
AB  - Proliferation of arterial smooth muscle cells (aSMC) is a key component of
      atherogenesis. A sample of 225 volunteers, aged 21-65 years, was exposed to
      "frustration," "harassment," or "relaxation," after completing the 50-item
      Hostility subscale of the Minnesota Multiphasic Personality Inventory (MMPI).
      Whole blood was measured before and after exposure for platelet-derived growth
      factor (PDGF), and sera were evaluated for total and HDL cholesterol
      concentrations and PDGF-independent mitogenic activity (SMA). Blood pressure and
      pulse rate were also evaluated. Analyses of SMA (i.e., serum independent of PDGF)
      revealed an increase in mitogenic effect for cultured human aSMC when hostility
      was treated as a dichotomous modifier. Among high-hostility subjects,
      surprisingly, those in the relaxed group and those with a lower educational level
      were found to have a significant mitogen response; no significant effects were
      observed for the low-hostility groups. The data suggest that endogenous stresses
      may occur in high-hostility individuals when "relaxed," to influence
      proliferation of arterial smooth muscle cells, as a contribution to
      atherogenesis. In individuals with lower educational levels and higher hostility
      scores, lifestyle changes may play a role.

PMID- 10088983
TI  - Relationship between physical and psychosocial dysfunction in Mexican patients
      with vertigo: a cross-cultural validation of the vertigo symptom scale.
AB  - The Vertigo Symptom Scale (VSS) was designed to assess and differentiate symptoms
      of: (a) balance disorder; and (b) somatic anxiety and autonomic arousal in
      patients complaining of dizziness and vertigo. Although it has been translated
      for use in countries other than the UK, where it was originally developed, its
      validity in different languages and cultures has not previously been evaluated.
      This study examined the structure, reliability, and discriminative power of a
      Spanish translation of the VSS administered to a Mexican sample of 172 dizzy
      patients and 40 healthy controls. Scores on the two subscales of the VSS not only
      discriminated between patients and controls, but were also sensitive to
      differences between patient groups classified on the basis of diagnosis, test
      results, and occupational disability. The pattern of intercorrelations between
      symptoms, anxiety, depression, and handicap in the Mexican sample was almost
      identical to that observed in the original UK sample.

PMID- 10088984
TI  - Prevalence of alexithymia and its association with sociodemographic variables in
      the general population of Finland.
AB  - The prevalence of alexithymia and its association with sociodemographic variables
      were studied in a sample of 1285 subjects representing the general population of
      Finland. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS
      20). Alexithymia was normally distributed in the population in both genders,
      confirming that it is a personality dimension. The prevalence of alexithymia was
      13%. Men were alexithymic almost twice (17%) as often as women (10%).
      Multivariate analysis showed that alexithymia was associated with male gender,
      advanced age, low educational level, and low socioeconomic status. As to the
      three factors of the TAS-20, men scored higher in factors 2 (difficulty in
      describing feelings) and 3 (externally oriented thinking). but there was no
      gender difference in factor 1 (difficulty in identifying feelings). Comparative
      population studies in other countries are needed to find out whether there are
      any differences in the prevalence of alexithymia between cultures.

PMID- 10088985
TI  - Socioeconomic status, social environment, depression and postdischarge adjustment
      of the cardiac patient.
AB  - In this study, we assess the adjustment achieved by patients following discharge
      from coronary care and the role of socioeconomic status (SES), social environment
      (SE), and depression in achieving that adjustment. Two hundred eighty-seven
      patients were enrolled. The SE into which the patients were to be discharged was
      rated significantly poorer for patients of lower SES, who also scored higher on
      depression. At 1, 6, and 12 months postdischarge, lower SES patients recorded
      significantly poorer levels of adjustment across a range of functioning.
      Predischarge depression, together with measures of SE and SES, determined 10% to
      28% of the variance in 12-month postdischarge adjustment. These data suggest the
      importance of identifying patients at greater risk for less than optimal outcome
      (those lower in SES and higher in depression), and the need to address the nature
      of the SE in which the patient has to effect his/her recovery.

PMID- 10088986
TI  - Effect of maternal diabetes on the fetal exocrine pancreas.
AB  - To test the hypothesis that fetal pancreatic exocrine and endocrine function are
      stimulated in parallel in the diabetic pregnancy, 68 mothers with gestational and
      pregestational diabetes who underwent amniocenteses after 34 weeks' for the
      evaluation of fetal lung maturity were enrolled. Amniotic fluid specimens were
      analyzed for C-peptide and trypsin content. Amniotic fluid specimens were
      obtained from 92 non-diabetic women undergoing amniocenteses for lung maturity,
      preterm labor, or premature rupture of membranes. Groups were compared using the
      Wilcoxon rank-sum test, Kruskal Wallis rank sum test, and Spearman's rank
      correlation test. C-peptide amniotic fluid concentrations were significantly
      greater in diabetics (median 0.6 ng/ml) than non-diabetics (median 0.4 ng/ml, P=
      0.0001), in pregestational (median 0.6 ng/ml) vs. gestational diabetics (median
      0.4 ng/ml, P = 0.006), and greater in proportion to severity of disease according
      to diabetic class (A1 = 0.4 ng/ml, A2 = 0.55 ng/ml, B = 0.6 ng/ml, C = 0.7 ng/ml,
      D = 0.85 ng/ml, P = 0.04). No significant differences were detected in amniotic
      fluid trypsin between the diabetic and non-diabetic or the gestational and non
      gestational diabetic groups. There was no correlation between C-peptide and
      trypsin within the diabetic groups. Stimulation of the exocrine and endocrine
      pancreas does not occur in parallel in the fetus of the diabetic mother. Although
      originating as a single organ, pancreatic exocrine and endocrine functions are
      distinct in both physiologic and pathologic conditions.

PMID- 10088987
TI  - Assessment of bone turnover in term and preterm newborns at birth: measurement of
      urinary collagen crosslink excretion.
AB  - We measured urinary excretion of collagen crosslinks, pyridinoline and
      deoxypyridinoline, in term and preterm newborns at birth and evaluated the
      developmental changes in bone turnover. Collagen crosslink excretion in newborns
      was more than 10 times higher than reported adult values and several times higher
      than those of older children. The values were significantly higher in preterm
      newborns than in term newborns. In addition, a significant and inverse
      correlation was found between urinary collagen crosslinks and gestational age in
      preterm newborns. Excretion of crosslinks during this period did not correlate
      with beta2-microglobulin, suggesting that the excretion was not directly
      influenced by renal function in newborns. We conclude that bone turnover assessed
      by measurement of collagen crosslink excretion is high at birth and that preterm
      newborns have higher bone turnover than term newborns.

PMID- 10088988
TI  - Outcomes of children of extremely low birthweight and gestational age in the
      1990's.
AB  - Advances in perinatal care have improved the chances for survival of extremely
      low birthweight (< 800 g) and gestational age (< 26 weeks) infants. A review of
      the world literature and our own experience reveals that at 23 weeks gestation
      survival ranges from 2% to 35%. At 24 weeks gestation the range is 17% to 58%,
      and at 25 weeks gestation 35% to 85%. Differences in population descriptors, in
      the initiation and withdrawal of treatment and the duration of survival
      considered may account for the wide variations in the reported ranges of
      survival. Major neonatal morbidity increases with decreasing gestational age and
      birthweight. The rates of severe cerebral ultrasound abnormality range at 23
      weeks gestation from 10% to 83%, at 24 weeks from 17% to 64% and at 25 weeks
      gestation from 10% to 22%. At 23 weeks gestation, chronic lung disease occurs in
      57% to 70% of survivors, at 24 weeks in 33% to 89%, and at 25 weeks gestation in
      16% to 71% of survivors. When compared to children born prior to the 1990's, the
      rates of neurodevelopmental disability have, in general, remained unchanged. Of
      30 survivors reported at 23 weeks gestation nine (30%) are severely disabled. At
      24 weeks gestation the rates of severe neurodevelopmental disability (including
      subnormal cognitive function, cerebral palsy, blindness and deafness) range from
      17% to 45%, and at 25 weeks gestation 12% to 35% are similarly affected. In
      Cleveland, Ohio, we compared the outcomes of 114 children with birthweight 500
      749 g born 1990-1992 to 112 infants born 1993-1995. Twenty month survival was
      similar (43% vs 38%). The use of antenatal and postnatal steroids increased (10%
      vs 54% and 43% vs 84%, respectively, P< 0.001), however the rates of chronic lung
      disease increased from 41% to 63% (P = 0.06). There was a significant increase in
      the rate of subnormal cognitive function at 20 months corrected age (20% vs 48%,
      P < 0.02) and a trend to an increase in the rate of cerebral palsy (10% vs 16%)
      and neurodevelopmental impairment. We conclude that, with current methods of
      care, the limits of viability have been reached. The continuing toll of major
      neonatal morbidity and neurodevelopmental handicap are of serious concern.

PMID- 10088989
TI  - Gestational age related changes in cardiac dynamics of the fetal baboon.
AB  - To provide insight into the maturation of neural mechanisms governing fetal heart
      rate and rate variability, seven chronically instrumented fetal baboons were
      monitored under steady state conditions between 120 and 165 days gestation (term
      175 d). Forty records of 24 h duration (5-7 records/fetus) were evaluated. For
      each fetus, heart rate decreased with gestational age (mean+/-SD, r = -0.530+/
      0.324, P <0.05). In contrast, there were increases with age in markers of various
      components of autonomic control of fetal R-wave to R-wave interval (RRi)
      variability as reflected in a positive correlation with age for all fetuses of SD
      RRi (r = 0.656+/-0.347, P < 0.01), root mean squared differences in RRi (r =
      0.686+/-0.223, P <0.05), and power at low frequency in the RRi spectrum (r =
      0.800+/-0.161 P < 0.01). In each of the seven fetuses, scatter plots of RRi as a
      function of the prior RRi (Poincare plots) had increased dispersion around the
      median with gestational age (0.605+/-0.371, P<0.05). Additional measures of
      variability evaluated changes in RRi from one interval to the next (deltaRRi).
      The incidence of sustained deltaRRi changes, either decelerations or
      accelerations, rose with gestation (r = 0.920+/-0.057, P < 0.001) while the
      incidence of no detected deltaRRi changes (<+/-1 ms) diminished (r = - 0.649+/
      0.364, P <0.05). Sequential decreases in fetal heart rate, increases in RRi
      variability and increases in changes in RRi and deltaRRi with age imply an
      overall maturation in autonomic cardio-regulatory control processes. Increases
      with gestation in measures of high frequency components of variability are
      compatible with enhanced parasympathetic modulation of fetal heart rate.

PMID- 10088990
TI  - Thrombopoietin (Tpo) in the fetus and neonate: Tpo concentrations in preterm and
      term neonates, and organ distribution of Tpo and its receptor (c-mpl) during
      human fetal development.
AB  - Little is known about thrombopoietin (Tpo) production in human fetuses and
      neonates. As a step toward determining whether Tpo is relevant to platelet
      production in the fetus and neonate, we hypothesized that: (1) like other
      cytokines, Tpo is present in the cord blood in higher concentrations than in
      adult plasma; (2) Tpo and its receptor (c-mpl) are expressed in fetuses at, and
      following, 5-6 weeks post-conception (when platelet production begins); and (3)
      the sites of Tpo and c-mpl production in the fetus are similar to those of
      adults. We quantified Tpo, by ELISA, in the plasma of 50 adults, as well as in
      the umbilical cord plasma of 50 preterm and term infants. We also characterized,
      by RT-PCR, the organ distribution of Tpo and c-mpl during fetal development (at 8
      and 16 weeks). Tpo concentrations were measurable (> or =41 pg/ml) in only two of
      the 50 adult samples (44 and 46 pg/ml), but in 24 of the 50 cord plasma samples
      (of the 24 samples, the median was 62 pg/ml; mean+/-SD, 80+/-39 pg/ml). Tpo
      levels did not correlate with either gestational age or platelet count at birth.
      Similarly to adults, in the fetal tissues, Tpo transcripts were found in all
      organs tested, but the most dense bands were from liver. C-mpl transcripts were
      also predominantly from liver. We conclude that: (1) Tpo is present in higher
      concentrations in cord plasma than in venous plasma of adults; (2) Tpo and c-mpl
      transcripts are detected in human fetuses as early as the onset of platelet
      appearance; and(3) Tpo and c-mpl have a similar organ distribution in fetuses and
      adults.

PMID- 10088991
TI  - Effects of discontinuing coffee intake on iron deficient Guatemalan toddlers'
      cognitive development and sleep.
AB  - Coffee is commonly given daily to toddlers in Guatemala. Possible negative
      effects of coffee ingestion on cognitive development and sleep patterns were
      assessed in 132 children 12-24 months of age who had received coffee for > 2
      months and were iron deficient on at least one indicator. Children were
      stratified by initial hemoglobin (A= anemic, Hgb < 10.5 g/dl; NA = 'non-anemic',
      Hgb > or = 10.5 g/dl) and were randomly assigned to an experimental group (S =
      substitute consisting of sugar and coloring), and a control group (C =
      continuation of coffee) (42 C-NA; 53 S-NA; 18 C-A; and 19 S-A). Anemic children
      were provided Fe supplements for 2-3 months. Compliance was assessed every 2
      weeks. After 5 months, testers masked to treatment group and anemia evaluated
      children with the Bayley Scales of Infant Development II in a central location.
      Scores were the Mental Development Index (MDI), the Psychomotor Development Index
      (PDI), and scales from the Behavior Rating Scale (BRS). The child's sleep in the
      previous 24 h was assessed with a set of standardized sleep questions to the care
      giver on the first visit and every 2 weeks thereafter. No significant effects of
      treatment on test scores or BRS ratings were found. In the 24 h period reported
      on at the final visit, children in the Substitute group slept more during the
      night and overall (night plus naps) than children in the Coffee group, a
      difference not found at the first visit. No differences were found in sleep
      difficulty or number of times waking at night. Women's reported coffee intake per
      day during pregnancy was associated with lower BRS ratings, even after
      controlling for SES and child age. The effects of postnatal coffee ingestion in
      Guatemala were seen for sleep duration, but not for cognitive development.
      Prenatal coffee ingestion was negatively associated with Behavior Rating Scales
      and should be investigated further.

PMID- 10088992
TI  - A meeting in honor of David Marr.

PMID- 10088993
TI  - The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal
      disorder.
AB  - Adrenoleukodystrophy (ALD) is caused by mutations in an ATP-binding-cassette
      transporter located in the peroxisomal membrane, which result in a fatal
      demyelinating disease in boys and a milder phenotype in men and some heterozygous
      women. There is no molecular signature to indicate a particular clinical course.
      The underlying molecular mechanisms of this disease have yet to be targeted
      clinically. Is the increase in very-long-chain fatty acids (VLCFA) the disease
      trigger? Why is there no phenotype in ALD null mice that show this increase? Do
      VLCFA destabilize human myelin, once formed, and lead to the inflammation seen in
      this genetic disease? Bone-marrow transplantation might save a child by providing
      normal brain macrophages and allowing myelin regeneration early in disease. The
      processes that underlie ALD challenge neuroscientists to elucidate peroxisomal
      transporter functions in the nervous system and to pursue the gene-transfer
      strategies leading to remyelination until a preventive therapy emerges.

PMID- 10088994
TI  - Ca2+-calmodulin and protein kinase Cs: a hypothetical synthesis of their
      conflicting convergences on shared substrate domains.
AB  - Evidence is accumulating that suggests that Ca2+-calmodulin (Ca2+-CaM) and the
      protein kinase Cs (PKCs) obstruct each other's actions because of the embedding
      of PKC phosphorylation sites in CaM or Ca2+-CaM-binding domains of a growing
      number of crucial substrates in neurons (and other cells). These substrates
      include the CaM storage proteins (neurogranin, neuromodulin), the membrane
      associated MARCKS (myristoylated alanine-rich C-kinase substrate) protein, the
      NMDA receptor RI subunit and the autoinhibitory domain of the plasma membrane
      Ca2+ pump. In this review, the emerging data are woven into a hypothetical
      picture of the conflicting, timing-dependent convergence of two major signalers
      on neuronal functions.

PMID- 10088995
TI  - Exploring the neurotransmitter labyrinth in nematodes.
AB  - Nematodes include both free-living species such as Caenorhabditis elegans and
      major parasites of humans, livestock and plants. The apparent simplicity and
      uniformity of their nervous system belies a rich diversity of putative signalling
      molecules, particularly neuropeptides. This new appreciation stems largely from
      the genome-sequencing project with C. elegans, which is due to be completed by
      the end of 1998. The project has provided additional insights into other aspects
      of nematode neurobiology, as have studies on the mechanism of action of
      anthelmintics. Here, progress on the identification, localization, synthesis and
      physiological actions of transmitters identified in nematodes is explored.

PMID- 10088996
TI  - Neuropeptide Y: emerging evidence for a functional role in seizure modulation.
AB  - The high concentration of the tyrosine-rich polypeptide, neuropeptide Y (NPY),
      and the increase in the number of its receptor subtypes that have been
      characterized in the brain, raise the question of a functional role for NPY in
      the CNS. In addition to its peripheral actions on cardiovascular regulation, much
      attention has, therefore, been devoted to the CNS effects of NPY because of its
      stimulatory properties on food intake, its role in anxiolysis and its putative
      involvement in memory retention. Emerging evidence points to an important role
      for NPY in the regulation of neuronal activity both under physiological
      conditions and during pathological hyperactivity such as that which occurs during
      seizures. This article reviews recent studies that have shown the changes induced
      by seizures in the level and distribution of NPY, its receptor subtypes and their
      respective mRNAs in rat forebrain. Biochemical and electrophysiological findings
      in experimental models and tissue from human epilepsy sufferers suggest that NPY
      mediated neurotransmission is altered by seizures. The pharmacological evidence
      and functional studies in NPY knockout mice highlight a crucial role for
      endogenous NPY, acting on different NPY receptors, in the control of seizures.

PMID- 10088997
TI  - The role of integrins in immune-mediated diseases of the nervous system.
AB  - Immune-mediated diseases of the CNS and PNS, such as multiple sclerosis and
      Guillain-Barre syndrome, respectively, constitute a major cause of transient and
      permanent neurological disability in the adult. The aetiology and pathogenesis of
      these disorders are only partially understood. On a cellular level, focal
      mononuclear-cell infiltration with demyelination and eventual axonal loss is a
      crucial pathogenetic event that leads to inflammation and subsequent dysfunction.
      Here, the evidence that integrins, a family of cell adhesion molecules, expressed
      on neural and immune cells might play a central role in immune cell recruitment
      to the CNS and PNS, and probably in tissue repair is reviewed. Distinct integrin
      expression patterns are observed in multiple sclerosis and Guillain-Barre
      syndrome. Therapeutic targeting of integrins has been very successful in the
      corresponding animal models and holds promise as a novel treatment strategy to
      combat human immune-mediated disorders of the nervous system.

PMID- 10088998
TI  - Is the Ras-MAPK signalling pathway necessary for long-term memory formation?
AB  - Genetic and pharmacological experiments have recently implicated several protein
      kinase cascades in LTP and memory formation. The small GTPases of the Ras
      subfamily are activated by multiple extracellular stimuli and, via a complex
      array of downstream effectors, they control a variety of cellular events that
      culminate in gene transcription. In the well-characterized Aplysia gill
      withdrawal reflex, activation of the Ras-dependent mitogen-activated protein
      kinase (MAPK) cascade is essential for the long-term, but not the short-term,
      facilitation process. In addition, in the rodent hippocampus, specific inhibition
      of the MAPK pathway significantly impairs the induction of LTP, which implicates
      this signalling cascade in hippocampal-dependent behaviour. Mice that lack the
      neuronal-specific Ras regulator, Ras-GRF (guanine-releasing factor), have
      severely impaired LTP in the amygdala and a corresponding deficit in long-term
      memory for aversive events. The results obtained from these different systems
      demonstrate the involvement of Ras-dependent signalling in neuronal plasticity
      and behaviour and raise a number of intriguing questions.

PMID- 10088999
TI  - Schizophrenia genetics: expansion of knowledge?

PMID- 10089000
TI  - Leptin and the hypothalamus: neuroendocrine regulation of food intake.

PMID- 10089001
TI  - NMDA receptors and nitric oxide synthase.

PMID- 10089002
TI  - What is the biological significance of an age-related increase in IL-1beta in
      hippocampus?

PMID- 10089003
TI  - The association of the short variant of the 5-HTTPLR polymorphism and the apoE
      epsilon4 allele does not increase the risk for late onset Alzheimer's disease.

PMID- 10089004
TI  - A bimodal model of the mechanism of action of lithium.
AB  - Investigations of the biochemical actions of lithium have identified many
      individual reactions that are affected, especially within cellular signaling
      systems, but the actions of lithium at different sites often appear opposing and
      difficult to integrate into a general mechanism of action. A bimodal mechanism of
      action of lithium is proposed which is in accord with many of the apparently
      contradictory results that have been published. This model describes the critical
      effect of lithium as that of a stabilizer of the magnitude of fluctuations of
      signaling processes. This is achieved by lithium balancing positive and negative
      regulators of signaling processes which results in lithium raising basal
      activities and diminishing maximal activities, thereby stabilizing signaling
      activities within an optimal range and preventing fluctuations either above or
      below this optimum. This model is shown to be applicable to many published
      results concerning the activation of AP-1 DNA binding and cyclic AMP production.
      Diverse sites of action of lithium are proposed to ultimately converge on the
      regulation of gene expression to contribute to mood stabilization.

PMID- 10089005
TI  - Brain choline acetyltransferase activity in chronic, human users of cocaine,
      methamphetamine, and heroin.
AB  - Cognitive impairment has been reported in some chronic users of psychostimulants,
      raising the possibility that long-term drug exposure might damage brain neuronal
      systems, including the cholinergic system, which are responsible for normal
      cognition. We measured the activity of choline acetyltransferase (ChAT), the
      marker enzyme for cholinergic neurones, in autopsied brain of chronic users of
      cocaine, methamphetamine, and, for comparison, heroin. As compared with the
      controls, mean ChAT levels were normal in all cortical and subcortical brain
      areas examined. However, the two of 12 methamphetamine users, who had the highest
      brain/blood drug levels at autopsy, had a severe (up to 94%) depletion of ChAT
      activity in cerebral cortex, striatum, and thalamus. Based on the subjects
      examined in the present study, our neurochemical data suggest that brain
      cholinergic neurone damage is unlikely to be a typical feature of chronic use of
      cocaine, methamphetamine, or heroin, but that exposure to very high doses of
      methamphetamine could impair, at least acutely, cognitive function requiring a
      normal nucleus basalis cholinergic neuronal system. Reduced brain ChAT might be
      explained in part by a hyperthermia-related mechanism as low ChAT levels have
      also been observed in brain of some patients with neuroleptic drug-associated
      hyperthermia. Studies of cognitive and brain cholinergic status in high dose
      users of MA are warranted.

PMID- 10089006
TI  - High seroprevalence of Borna virus infection in schizophrenic patients, family
      members and mental health workers in Taiwan.
AB  - Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be
      associated with severe psychiatric disorders. The association is mainly based on
      the findings that patients with schizophrenia and depression have a higher
      seroprevalence rate of BDV-specific antibodies than controls. In addition,
      psychiatric patients were also found to have a higher detection rate of BDV
      transcripts in their blood than controls. By using an improved Western blot
      analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan
      also have a higher seroprevalence of BDV-specific antibodies than controls (12.1%
      vs 2.9%, P< 0.001), providing support to the positive association between BDV and
      psychiatric disorders in our population. Because of the contagious nature of
      viral infection, we further examined patients' family members and mental health
      workers, who have close contact with patients. We found that both groups also
      have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%,
      respectively, than controls. This finding provides some evidence for a possible
      human-to-human transmission of Borna disease virus. Our finding needs further
      independent verification from other research groups and the clinical relevance of
      this preliminary observation deserves further study.

PMID- 10089007
TI  - Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in
      schizophrenia: a possible neurochemical basis for 'hypofrontality'.
AB  - An impairment of prefrontal cortical functioning in schizophrenia
      ('hypofrontality') has been suggested by clinical, neuroimaging, and postmortem
      brain tissue studies. We used Western immunoblot and Northern hybridization
      analyses of postmortem brain tissue obtained from 14 schizophrenic patients and
      12 control patients of similar ages to measure tissue levels of synaptophysin (a
      structural synaptic vesicle protein) and of SNAP-25 (a 25-kDa presynaptic
      protein), and their encoding mRNAs, in Brodmann's area 10 of prefrontal cortex.
      There were significant decreases in tissue levels of both of these proteins in
      prefrontal cortex of schizophrenic patients relative to controls. In contrast,
      tissue levels for the mRNAs encoding these proteins were not decreased in
      schizophrenic patients. Subsequent labeling of the same Western immunoblots
      showed no difference in tissue levels of glial fibrillary acidic protein (GFAP)
      in schizophrenic and control patients. Similarly, subsequent hybridization of the
      same Northern hybridization membranes showed no difference in tissue levels of
      GFAP mRNA or of 28S rRNA in schizophrenic and control patients. These alterations
      in tissue levels of synaptophysin and SNAP-25 are consistent with the idea that
      the clinically observed 'hypofrontality' of schizophrenia arises from
      abnormalities of synaptic number or structural integrity in prefrontal cortex.

PMID- 10089008
TI  - Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in
      the human prefrontal cortex patients with schizophrenia, bipolar disorder, and
      depression.
AB  - L1 and Thy-1 are members of the immunoglobulin (Ig) superfamily of cell adhesion
      molecules (CAMs) that are vital for normal neural development. Abnormalities in
      CAM expression could lead to the histological abnormalities that have previously
      been described in the frontal cortex of patients with schizophrenia. A postmortem
      immunohistochemical study of L1 and Thy-1 in the normal human prefrontal cortex
      revealed positive immunostaining of axons in all layers of the cortex.
      Quantifying the intensity of immunostaining in the prefrontal cortex of patients
      with schizophrenia, bipolar disorder and depression failed to reveal any
      significant differences when compared to that of normal controls.

PMID- 10089009
TI  - Polyglutamine-containing proteins in schizophrenia.
AB  - Genetic anticipation, manifested by increased severity and earlier age-at-onset
      of the disease over successive generations, is reported in schizophrenia. The
      molecular basis of anticipation in several neurodegenerative diseases is unstable
      coding CAG repeat expansions. Anticipation was reported in schizophrenia.
      Recently, studies suggested that enlarged CAG/CTG repeats are over represented in
      schizophrenic patients compared to normal controls. Together, these observations
      suggest that unstable CAG repeats may play a role in the etiology of
      schizophrenia. The purpose of this study is to test for the presence of
      polyglutamine-expanded tracts, encoded by CAG repeats, in total protein extracts
      derived from lymphoblastoid cell lines of schizophrenic patients. Proteins from
      schizophrenic patients (n = 59) and normal controls (n = 73) were separated by
      means of SDS-polyacrylamide gel electrophoresis, wet blotted onto nitrocellulose
      membrane and probed with a monoclonal antibody (mab 1C2) recognizing expanded
      polyglutamine arrays. Three abnormal bands corresponding to protein(s) of
      molecular weight of approximately 50 kDa were identified in two unrelated
      schizophrenic patients and in a sibling of one of these patients. None of the
      normal controls tested positive for this abnormal band. These results suggest
      that expanded polyglutamine-containing proteins, though rare, may play a role in
      the pathogenesis of schizophrenia.

PMID- 10089010
TI  - Detection of polyglutamine expansion in a new acidic protein: a candidate for
      childhood onset schizophrenia?
AB  - Polyglutamine expansion (PGE) encoded by a CAG repeat underlies eight inherited
      neurodegenerative diseases, among which is Huntington's disease. CAG expansion
      has also been reported in schizophrenia, suggesting a role for PGE. To
      investigate the potential role of PGE as a candidate for schizophrenia, we
      searched for PGE in nuclear families comprising a patient affected by childhood
      onset schizophrenia (COS, a rare and severe form of the disease) as a variation
      of the candidate gene approach for identifying susceptibility genes. We tested
      lymphoblastoid cell lines from COS patients (n = 32) by Western blot analysis
      with 1C2, a monoclonal antibody that specifically recognizes long polyglutamines.
      Eight of 11 unrelated black American COS patients showed a 60-kDa (approximately)
      band indicative of PGE. A strong 60-kDa band (suggestive of a large PGE) was
      detected in two of the eight positive patients. A weaker 60-kDa band (suggestive
      of a smaller and non pathogenic PGE) was detected in some unaffected parents or
      sibs of these two COS patients, and in six other black American COS patients. The
      strong and weak PGE signals were found to correspond to two different proteins.
      Unrelated black Americans unaffected by COS (n = 38) were negative for the strong
      60-kDa PGE signal. Healthy white Americans (n = 53) were negative for both the
      strong and weak 60-kDa PGE signals. Two-dimensional gel analysis suggested that
      the strong PGE signal corresponds to an acidic (pI 4 approximately) protein and
      resulted in a more precise estimation (52-57 kDa) of its relative mass. This
      protein appeared to be not represented in Genbank, as suggested by the exclusion
      of several candidate CAG repeats. Our data suggest that this acidic protein might
      be a candidate for COS.

PMID- 10089011
TI  - Mutation screening of the UBE3A/E6-AP gene in autistic disorder.
AB  - Previous reports of individuals with autistic disorder with maternal duplications
      of 15q11-q13, the Prader-Willi/Angelman syndrome region, suggest this area as a
      source of candidate genes in autistic disorder. Maternal truncation mutations in
      UBE3A, which encodes for E6-AP ubiquitin-protein ligase, have been shown to cause
      Angelman syndrome, which can also result from the absence of maternal chromosomal
      material from this region. Despite showing no evidence for imprinting in other
      tissues, this gene was recently discovered to be preferentially maternally
      expressed in human brain and expressed solely from the murine maternal chromosome
      in the hippocampus and cerebellar Purkinje cells, regions implicated in the
      neuropathology of autism. Based on this evidence, the coding region and a
      putative promoter region were sequenced in ten autistic subjects. Several
      polymorphisms were detected, but no evidence was found for a functional mutation.
      Evidence for likely altered regulation of UBE3A expression in maternal 15q11-q13
      duplications suggests further investigation of the regulatory regions of this
      gene in autistic disorder.

PMID- 10089012
TI  - Association between a marker in the UCP-2/UCP-3 gene cluster and genetic
      susceptibility to anorexia nervosa.
AB  - Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of
      the at risk population in the UK which equates to approximately 70000 sufferers.
      Data from a number of studies have demonstrated the heritability of this
      disorder, however it is only in the last few years that studies have begun to
      determine the involvement of particular candidate genes in this genetic
      predisposition. In the current study we have used classical case-control
      association analysis to determine whether two highly polymorphic microsatellite
      markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement
      of this region of the human genome in the predisposition to AN. Analysis of a
      cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female
      controls shows evidence of association with the marker D11S911 but not D11S916.
      Allele 13 of the marker D11S911 is significantly over represented in the anorexia
      nervosa population suggesting that a mutation in linkage disequilibrium with this
      locus may form part of the genetic component of AN. Further work is now required
      to try to reproduce these data in a second independent cohort and to further
      characterise this region of the human genome.

PMID- 10089013
TI  - Serum leptin and gonadotropin levels in patients with anorexia nervosa during
      weight gain.
AB  - Leptin plays an important role in reproductive function. In patients with acute
      anorexia nervosa, serum leptin levels have repeatedly been shown to be lower than
      in age-matched controls. We have previously hypothesized that the amenorrhea
      characteristic of anorexia nervosa is related to this low leptin secretion. In an
      attempt to address this hypothesis, serum levels of leptin and follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) of 16 female inpatients
      with anorexia nervosa or an eating disorder not otherwise specified (atypical
      anorexia nervosa) were measured on a biweekly basis during weight gain. We
      hypothesized that a serum leptin level of 1.85 microg L(-1) would be associated
      with gonadotropin levels at or above the minimal level observed during the
      menstrual cycle in healthy adult fertile females. Our results revealed that
      increments of LH levels generally tracked increments of leptin levels during the
      first weeks of treatment. Similarly, in those patients with low referral leptin
      levels, FSH initially also tracked leptin levels. In contrast, a relationship
      between gonadotropin levels and leptin secretion was no longer discernible after
      LH and FSH levels had peaked. Those patients with exceedingly low leptin levels
      upon admission revealed a slow increase of gonadotropin levels. Our hypothesis of
      a threshold leptin level of 1.85 microg L(-1) was supported for LH only.

PMID- 10089014
TI  - Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample
      of 57 German families.
AB  - Previously reported linkage of bipolar affective disorder to DNA markers on
      chromosome 18 was reexamined in a large sample of German bipolar families. Twenty
      three short tandem repeat markers were investigated in 57 families containing 103
      individuals with bipolar I disorder (BPI), 26 with bipolar II disorder (BPII),
      nine with schizoaffective disorder of the bipolar type (SA/BP), and 38
      individuals with recurrent unipolar depression (UPR). Evidence for linkage was
      tested with parametric and non-parametric methods under two definitions of the
      affected phenotype. Analysis of all 57 families revealed no robust evidence for
      linkage. Following previous reports we performed separate analyses after
      subdividing the families with respect to the sex of the transmitting parent.
      Fourteen families were classified as paternal and 12 families as maternal. In 31
      families the parental lineage of transmission of the disease could not be
      determined ('either' families). Evidence for linkage was obtained for chromosomal
      region 18p11.2 in the paternal families and for 18q22-23 in the 'either'
      families. The findings on 18p11.2 and 18q22-23 support prior evidence for
      susceptibility loci in these regions. The parent-of-origin effect on 18p11.2 is
      confirmed in our sample. The delineation of characteristics of 'either' families
      requires further study.

PMID- 10089015
TI  - Association of a polymorphism of the 5HT2A receptor gene promoter region with
      alcohol dependence.
AB  - Approximately 10% of Japanese alcoholics develop their disease despite having an
      inactive form of aldehyde dehydrogenase-2 (ALDH2), known as a genetic deterrent
      of heavy drinking due to adverse reactions after drinking. Such alcoholics are
      considered to be advantageous in genetic research because they should show
      reduced heterogeneity and possess genetic factors conferring susceptibility to
      alcohol dependence. Examination of the -1438 A/G polymorphism of the serotonin 2A
      (5HT2A) receptor gene in 225 Japanese alcoholics with inactive ALDH2 revealed the
      presence of significantly more of the G allele than was found in 361 control
      subjects. The frequency of the G allele in 282 alcoholics with active ALDH2 fell
      between the G allele frequencies of controls and subjects with inactive ALDH2.
      These data suggest that although the effect is relatively small, genetic
      variability in the 5HT2A receptor is involved in the development of alcohol
      dependence.

PMID- 10089016
TI  - Association between seasonal affective disorder and the 5-HT2A promoter
      polymorphism, -1438G/A.
AB  - Genes involved in serotonin metabolism are good candidates for the pathogenesis
      of seasonal affective disorder (SAD). A functional variant in the serotonin
      transporter promoter, 5-HTTLPR, has recently been shown to be associated with SAD
      and seasonality. The purpose of this study was to determine whether -1438G/A, a
      polymorphism in the 5-HT2A promoter, is associated with SAD and seasonality, and
      whether it has additive effects with 5-HTTLPR on seasonality. Sixty-seven
      individuals with SAD and 69 normal volunteers, all screened with the SCID and
      diagnosed according to DSM-III-R criteria, were genotyped for the -1 438G/A 5
      HT2A promoter polymorphism. All had been previously genotyped for 5-HTTLPR and
      had been assessed for seasonality by the Global Seasonality Scale. There was a
      significant increase in the frequency of the -1438A variant allele of the 5-HT2A
      promoter polymorphism in SAD patients (0.47) compared to matched controls (0.36)
      (P < 0.01). The difference in genotype distribution was also significant (P <
      0.05). We found no association between the -1438G/A polymorphism and seasonality
      scores, and there was no additive effect with 5-HTTLPR on seasonality. In
      conclusion, we have shown that the -1438G/A 5-HT2A promoter variant is associated
      with SAD but not with seasonality. We suggest that the association may instead be
      with the depressive symptoms of SAD. However, these results should be treated
      with caution until replicated because of the possibility of false-positive
      findings in case-control association studies.

PMID- 10089017
TI  - Neuroticism is not associated with the serotonin transporter (5-HTTLPR)
      polymorphism.
AB  - A deletion/insertion polymorphism in the transcriptional control region of the
      serotonin transporter gene (5-HTTLPR) was reported to be associated with
      dimensional measures of neuroticism, although subsequent replication attempts
      have failed. These replication attempts, however, have been dissimilar to the
      initial study in sample size, distribution of allelic frequency and/or assessment
      of neuroticism. The current study was conducted in a further attempt to replicate
      the initial finding using: (a) a sample that was more comparable to each of the
      individual samples in the initial report; and (b) identical psychometric
      methodology to assess neuroticism. Two hundred and twenty-five Caucasian adults
      were genotyped for the 5-HTTLPR polymorphism and completed the NEO Personality
      Inventory. Results did not replicate the association between the 5-HTTLPR
      polymorphism and neuroticism; individuals with the short form of this variant did
      not report higher NEO Neuroticism. Indeed, men with the short form reported lower
      Anxiety, a finding that is directionally opposite to the initial results. These
      findings, combined with other failures to replicate, indicate that the
      reproducibility of the association between the 5-HTTLPR polymorphism and
      neuroticism must be regarded as questionable. The contradictory findings suggest
      the need for a replication attempt in a large, normative sample that is
      stratified by ethnicity and sex.

PMID- 10089018
TI  - A novel allele in the promoter region of the human serotonin transporter gene.
AB  - The human serotonin transporter (hSERT) gene is a promising candidate for
      mediating the genetic susceptibility for various psychiatric conditions such as
      mood and obsessive-compulsive disorders. Two polymorphic sites in this gene
      attracted much interest: a VNTR of 17-bp repeats in intron two, and an
      insertion/deletion in the 5'-flanking promoter region (5-HTT gene-linked
      polymorphic region-5-HTTLPR) creating a short (S) and a long (L) allele. The 5
      HTTLPR polymorphism is situated in a GC-rich region composed of 20-23 bp
      repeating units. The S and L alleles have 14 and 16 repeat-elements respectively.
      Positive associations of the 5-HTTLPR polymorphism with mood disorders, anxiety
      related personality traits, autism and late-onset Alzheimer's disease have been
      published, although some non replications were also reported. Here we report a
      novel allele (termed LJ) in the 5-HTTLPR site. This allele is longer than the L
      allele by 43 bp, has 18 repeat units and contains two copies of the
      insertion/deletion sequence arranged in tandem. The LJ allele was found in
      individuals of Libyan and Tunisian Jewish origin but not in Moroccan or Ashkenazi
      Jews.

PMID- 10089019
TI  - Molecular pathogenesis of chronic myeloid leukemia: implications for new
      therapeutic strategies.
AB  - With an annual incidence of about ten in 1,000,000 people, chronic myeloid
      leukemia (CML) accounts for most cases of myeloproliferative disease and for 20%
      of all leukemias. While novel therapies such as treatment with interferon-alpha
      or bone marrow transplantation have successively improved the outcome of CML
      treatment, hope for future progress in the therapy of CML lies in an almost
      unique feature of this hematological malignancy. In contrast to many other forms
      or subforms of leukemias which display a great diversity in chromosomal
      alterations, most cases (>95%) of CML seem to be caused by an almost invariably
      found cytogenetic aberration, the so-called Philadelphia chromosome (Ph),
      resulting in the bcr-abl fusion gene. Its gene product, p210bcr-abl (Bcr-Abl), is
      believed to be essential for hematopoietic cell transformation and seems to exert
      its effects by interfering with cellular signal transduction pathways, normally
      involved in the control of cell death and proliferation. Several partially
      interacting pathways have been shown to be induced by Bcr-Abl. The role of most
      of them is still unclear and, as understanding their biological functions should
      lead to novel therapeutic strategies on a molecular basis, much effort is spent
      on identifying their precise roles in CML. This review focuses on our current
      understanding of Bcr-Abl-induced signal transduction and outlines its importance
      for the biological effects of Bcr-Abl.

PMID- 10089020
TI  - Prognostic impact of apoptosis and proliferation in idiopathic (primary)
      myelofibrosis.
AB  - A retrospective study of 120 patients with the clinically and histologically
      established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed
      to determine prognostic factors of predictive value, including parameters
      characterizing the dynamics of hematopoietic cell kinetics. In contrast to
      previous studies, our cohort comprised the full spectrum of the disease, from
      initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling
      (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic
      parameters of predictive value. Cell proliferation was evaluated by employing the
      monoclonal antibody PC10 directed against proliferating cell nuclear antigen
      (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed
      significant differences between early and advanced fibrosclerotic stages of
      disease. Decrease in proliferation indicated a significantly shorter survival,
      whereas a higher frequency of apoptotic cells was associated with a better
      prognosis. It may be speculated that a normal or enhanced proliferation rate
      expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is
      accompanied by a higher incidence of apoptosis reflects the regenerative
      (turnover) capacity of hematopoiesis. This may apply especially to early
      hypercellular stages without relevant myelofibrosis. In consideration of a
      recently published multivariate risk model, a simplified synthesis score for
      stratification of a patient's prognosis was constructed. Age, degree of anemia,
      leukocytes, and platelet count were regarded as the most important parameters. A
      substantial improvement of prognostic efficiency was further achieved by
      including PCNA index and frequency of apoptosis. Our results are in keeping with
      the assumption that generalization, indicated by myeloid metaplasia, has a
      prodigious impact on prognosis in IMF. Furthermore, in this context dynamic
      features such as proliferative activity and frequency of apoptosis exert an
      additional predictive value.

PMID- 10089021
TI  - Suppressed neutrophil function as a risk factor for severe infection after
      cytotoxic chemotherapy in patients with acute nonlymphocytic leukemia.
AB  - Severe infections are a major problem in patients suffering from acute
      nonlymphocytic leukemia (ANLL) undergoing myeloablative chemotherapy. Possible
      factors leading to infectious complications in these patients are suppressed
      immune defense mechanisms existing prior to therapy, including those involving
      the neutrophil granulocyte department. In this study we investigated whether
      neutrophil function as measured by oxidative burst and phagocytosis before the
      start of treatment correlates with the severity of infection after therapy. Forty
      four patients were included, 27 men and 17 women. Their median age was 46 years
      (range 20-70 years). According to the development of infectious complications the
      patients were assigned retrospectively to group 1 (no or only mild infections, n
      = 29) or to group 2 (severe infection or death due to infection, n = 15). The
      phagocytic activity was significantly reduced in group 2 as compared with group 1
      [113.7+/-13.7 (SEM) vs 170.0+/-19.2, mean channel fluorescence; p =0.04]. In
      contrast, the oxidative burst as measured by FMLP stimulation was pronounced but
      not significantly enhanced in group 2 (24.8+/-6.1 vs 14.5+/-3.4, mean channel
      fluorescence). In conclusion, patients with severe infections after chemotherapy
      might already have preactivated neutrophils with suppressed function prior to
      treatment. Thus, evaluating function parameters could help to estimate the
      individual risk of infection for a patient with ANLL.

PMID- 10089022
TI  - Leukocytoclastic vasculitis as a complication of granulocyte colony-stimulating
      factor (G-CSF) -- a case study.

PMID- 10089023
TI  - Severe aplastic anemia associated with human parvovirus B19 infection in a
      patient without underlying disease.
AB  - Human parvovirus B19 (B19 virus) infection is known to induce aplastic crisis in
      patients with hemolytic anemia. In healthy subjects, B19 infection may sometimes
      cause mild pancytopenia, but these changes are transient and recovery is
      spontaneous. We report the first case of aplastic anemia in a previously healthy
      boy without any underlying diseases, following asymptomatic infection with the
      B19 virus. Laboratory examination initially showed thrombocytopenia, mild
      leukopenia in the peripheral blood, and severe hypoplastic bone marrow. Since
      pancytopenia developed and worsened progressively, immunosuppressive therapy was
      given, resulting in a complete remission. Despite the lack of an infectious
      prodrome, serological and histological analysis revealed an underlying infection
      with the B19 virus. Thus, B19 virus infection must be considered one of the
      causes of aplastic anemia in patients without underlying hemolytic anemia and an
      apparent episode of the viral infection.

PMID- 10089024
TI  - Complete remission of refractory anemia following a single high dose of
      cyclophosphamide.
AB  - We describe a case of stable complete remission in a patient with refractory
      anemia complicated by severe autoimmune hemolytic anemia, achieved with a single
      high dose (4 g/m2) of cyclophosphamide (cyclo). Concomitantly, an effective
      mobilization of CD34-positive cells was induced. Other immunosuppressive
      approaches including high-dose methylprednisolone, high-dose immunoglobulin, and
      cyclosporine had been ineffective. This finding suggests that, in selected cases,
      an immunologic mechanism may mediate cytopenia in myelodysplastic syndromes
      (MDS). In addition, it demonstrates that successful mobilization of peripheral
      blood stem cells can be induced with high-dose cyclo in MDS.

PMID- 10089025
TI  - Spontaneous remission in myelodysplastic syndrome.
AB  - A 73-year-old man was admitted for investigation of pancytopenia. His physical
      examination was unremarkable and the bone marrow aspirate was compatible with
      myelodysplastic syndrome (RAEB). Cytogenetic analysis of the bone marrow revealed
      a trisomy 21. The patient received transfusions of packed red cells, and his
      condition remained stable for the next 7 months. He was then admitted with a
      chest infection and was treated with broad-spectrum antibiotics with satisfactory
      response. During his hospitalization there was a gradual increase in his complete
      blood count values, which persisted, resulting in a normal peripheral blood after
      3 months. A bone marrow aspirate performed at that time revealed normal findings
      with no karyotypic abnormalities, indicating a spontaneous remission. The patient
      remained stable for the next 6 months; then he recurred with 20% blasts in his
      bone marrow and reappearance of trisomy 21 in 42% of the metaphases examined.
      Several hematologic malignancies with spontaneous remissions have been described
      to date, but they have generally been short and recurrence is the rule, as in the
      case described. The role of endogenous cytokines in triggering these spontaneous
      remissions is under question, as the exact mechanism is unknown.

PMID- 10089026
TI  - Splenic rupture in a patient with acute myeloid leukemia undergoing peripheral
      blood stem cell transplantation.
AB  - Splenic rupture is a rare but well-recognized complication of hematological
      malignancies. Here, we present the case of a 22-year-old woman with the diagnosis
      of acute myeloid leukemia who was undergoing peripheral blood stem cell
      transplantation. On day + 10 she developed a hypovolemic shock due to rupture of
      her spleen and went to emergency laparotomy. This is the first report of splenic
      rupture during peripheral blood stem cell transplantation.

PMID- 10089027
TI  - Mandibular mass as the presenting manifestation of IgM myeloma in a 22-year-old
      man.
AB  - We report here the youngest known IgM myeloma patient to have presented with a
      mandibular mass. A 22-year-old Chinese man sought medical attention due to a mass
      over his right mandible that had been growing progressively for 6 months. A
      solitary osteolytic lesion in the right mandible was identified radiologically.
      Incisional biopsy revealed the presence of plasma cells of monoclonal origin, as
      evidenced by the exclusively positive staining of the kappa light chain. The
      diagnosis of multiple myeloma with mandibular involvement was confirmed by bone
      marrow examination. Further tests, including immunoglobulin electrophoresis and
      assay of the serum levels of kappa and lambda light chains, demonstrated that his
      myeloma was of the IgM, kappa subtype. The patient achieved a nonsustained
      partial response to six courses of melphalan and prednisolone therapy and
      palliative radiotherapy.

PMID- 10089028
TI  - Hodgkin's and Castleman's disease in a patient with systemic mastocytosis.
AB  - Systemic mastocytosis is a rare condition characterized clinically by the local
      consequences of vasoactive peptides released from infiltrating mast cells in the
      reticuloendothelial tissues. Mast cells originate from the pluripotent bone
      marrow stem cells; it is therefore not surprising that myeloproliferative and
      myelodysplastic disorders commonly coexist or terminate the clinical phase of
      mastocytosis. We report here, to our knowledge, the first case of Hodgkin's and
      Castleman's disease occurring in a patient with co-existent systemic
      mastocytosis, which remained unchanged after combination chemotherapy for
      Hodgkin's disease.

PMID- 10089029
TI  - Clonal expansion of gammadelta-T lymphocytes in an HTLV-I carrier, associated
      with chronic neutropenia and rheumatoid arthritis.
AB  - We report on an HTLV-I carrier showing clonal proliferation of gammadelta-T
      lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A
      75-year-old Japanese woman had a 20-year history of RA and was found to have
      neutropenia and lymphocytosis by routine examinations. Her white cell count was
      5,800/microl with 89% lymphocytes. The proliferating gammadelta-lymphocytes did
      not show the typical morphology of large granular lymphocytes (LGL) and were
      positive for CD3, TCRdelta1, and HLA-DR but negative for CD4, CD8, and deltaTCS1.
      Clonally rearranged TCRgamma-chain (Jgamma) and TCRbeta-chain (Cbeta1) genes were
      detected by Southern blot analysis. Clonality of these proliferating gammadelta-T
      cells was confirmed by CDR3 size analysis for the TCRdelta-chain. Anti-HTLV-I
      antibody was positive and the pX region of HTLV-I proviral DNA was detected by
      PCR analysis, but clonal integration of HTLV-I proviral DNA was not detected by
      Southern blotting analysis. The patient's clinical course has been stable, except
      for infrequent infectious episodes. The association of HTLV-I/II infection with T
      LGL leukemia has been reported by several groups, although most cases exhibit
      TCRalphabeta+ type T cells. Analysis of the junctional sequence of TCR on T-LGL
      leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell
      proliferation.

PMID- 10089031
TI  - Irreversible renal failure in a patient with chronic lymphocytic leukemia treated
      with fludarabine.

PMID- 10089030
TI  - Downbeat nystagmus caused by thiamine deficiency: an unusual presentation of CNS
      localization of large cell anaplastic CD 30-positive non-Hodgkin's lymphoma.
AB  - A 24-year-old woman with a large cell anaplastic CD 30-positive T-cell non
      Hodgkin's lymphoma (NHL) developed downbeat nystagmus, anisocoria, and
      oscillopsia. Prior to overt cerebral invasion by NHL, she had a thiamine
      deficiency with very low thiamine concentrations in the CSF, probably caused by
      protracted vomiting and increased vitamin B1 consumption by intrathecal tumor
      cells. We believe that her neurologic symptoms were caused -- at least partly --
      by thiamine deficiency, as she reacted well to thiamine supplementation at the
      beginning of treatment.

PMID- 10089032
TI  - Anatomy of the internal branch of the superior laryngeal nerve.
AB  - The purpose of this study was to determine the length and distribution of the
      branches of the internal branch of the superior laryngeal nerve (ibSLN) and
      describe the initial afferent pathway for the laryngeal cough reflex (LCR). On 25
      sides of 19 cadaver specimens, the ibSLN and its branches were dissected from the
      greater cornu of the hyoid to the mucosa of the larynx and laryngopharynx. The
      location of these terminal fibers were confirmed by direct observation and
      fiberoptic laryngoscopy. In 21 specimens, the ibSLN coursed 6.95+/-3.71 mm before
      piercing the thyrohyoid membrane and splitting into superior, middle, and
      inferior rami. Four specimens split proximal to the thyrohyoid membrane. The
      superior ramus distributed to the mucosa of the piriform recess. In this study
      the large, middle ramus was a new finding and distributed branches to the mucosa
      of the vestibule of the larynx, specifically the quadrangular membrane. The
      length of the ibSLN from the greater cornu to the end of the middle ramus at
      quadrangular membrane was 28.52+/-4.61 mm. The termination of these fibers were
      confirmed by observation and direct laryngoscopy. The middle ramus probably
      conveyed the afferent component of the laryngeal cough reflex. The inferior ramus
      did not distribute to the vestibular mucosa.

PMID- 10089033
TI  - Application of obstetric ultrasound to determine the most suitable parameters for
      the aging of formalin-fixed human fetuses using manual measurements.
AB  - The aim of this study was to find the most suitable manual measurements to
      estimate the age of preserved fetuses. A new technique was used to make
      successful ultrasonic measurements on 86 out of 100 preserved fetuses under
      conditions simulating the intrauterine environment. The ultrasonographic images
      of the preserved specimens were very similar to those of live fetuses. Ultrasonic
      measurements of standard parameters, and the ages derived from them, were
      computed directly by the ultrasound scanning machine. Manual measurements were
      made of the same parameters using established techniques and standard tables for
      estimating fetal age. The measurements and the ages obtained for each parameter
      by the two techniques were statistically compared using the limits of agreement
      (Bland and Altman, 1986). Of the manual measurements used in the estimation of
      fetal age, foot length was found to be the most suitable parameter for practical
      use. Biparietal diameter was equally good, but the head circumference was the
      most precise, especially when used in conjunction with the formulae developed for
      ultrasonic measurements. Crown-rump length was found to be unsuitable to age
      fetuses beyond the first trimester due to distortion of the spine caused by
      compression in storage.

PMID- 10089034
TI  - Anatomical bases of glottic widening surgery related to arytenoidectomy.
AB  - Derived from arytenoidectomy, different surgical techniques have been developed
      for widening the glottis in cases of bilateral vocal cord paralysis. Their
      anatomical bases were reinvestigated in plastinated serial sections of 25 adult
      human larynges. At the anterolateral surface of the arytenoid cartilage, blood
      vessels crossing the crista arcuata may cause bleeding complications. The
      arytenoid cartilage is related to three major histologic complexes which must be
      taken into account during surgery. The dense connective tissue complex consists
      of the cricoarytenoid ligament and the conus elasticus, which are connected
      ventrocaudally. The cricoarytenoid ligament and the vocal cord are separated by
      the cartilaginous inscription of the vocal process. The muscular complex consists
      of the transverse arytenoid muscle, which is the posterior wall of the glottis,
      and the thyroarytenoid muscle, which is intimately fixed to the conus elasticus
      near the arytenoid cartilage. The loose connective tissue complex is represented
      by the vestibular fold, containing adipose tissue, mucous glands, few collagenous
      fiber septa, and at its posterior end, a small cranial extension of the vocal
      cord. For glottic widening surgery, the arytenoid cartilage must be regarded as
      an integrated component of an extended fibro-cartilaginous framework supporting
      the laryngeal airway. Shrinking processes of the dense connective tissue elements
      may complicate surgical interventions. Iatrogenic lesions of the posterior
      glottis should be avoided to prevent the development of synechia or insufficient
      closure of the larynx during swallowing.

PMID- 10089035
TI  - Osteophytosis of the cervical spine in South African blacks and whites.
AB  - Cervical vertebral columns (214) of adult human skeletons belonging to South
      African blacks and whites were examined for the presence of osteophytes. It was
      found that the cervical vertebrae of the black samples were significantly less
      affected by degenerative changes than in the whites. This finding has specific
      clinical implications in that the distribution of osteophytosis in the blacks
      also follows a different pattern than in the whites; osteophytes appear to affect
      either the vertebral body or apophysial joint facets in the cervical vertebrae of
      the blacks. In the whites, in sharp contrast, both sites are often affected on
      the same vertebra, which in life may result in a pincer-like entrapment of the
      spinal nerve root and/or vertebral artery. Consideration is given to the possible
      physiological and/or functional causes of the differences in distribution and
      pattern of development of osteophytes in the cervical spines of the two
      population groups.

PMID- 10089036
TI  - Teaching and learning gross anatomy: dissection, prosection, or "both of the
      above?".

PMID- 10089037
TI  - Anatomy teaching for medical undergraduates: general practice as a guideline? The
      brain.
AB  - Basic science teaching, particularly the teaching of gross anatomy, is at present
      a highly controversial topic. How much and what kind of anatomy should be taught
      to medical undergraduates nowadays? In conducting the present study we based our
      proposals on the criterion of general medical relevance. Therefore, we sent an
      anatomical questionnaire to a sample of Swiss general practitioners. Here, we
      present the results derived from questions on the human brain, discussing them in
      connection with the other organs so far investigated. The results obtained
      suggest that a common body of anatomical knowledge appropriate for the field of
      general medical practice does in fact exist. We believe that this basic stock can
      serve as a guideline for decision makers involved in the development of
      curricula, which can be fitted into the time frame available for anatomy teaching
      today while still guaranteeing a sound level of competence required for general
      practice of medicine. We also hope that this approach may serve as a model for
      the teaching of other basic sciences.

PMID- 10089038
TI  - Human anatomical science and illustration: the origin of two inseparable
      disciplines.
AB  - From the early wall paintings of ancient Egyptians to the recent advent of
      computer graphics, medical illustrators have employed a variety of techniques and
      materials to enrich the art of medicine. Over the centuries, medical illustrators
      have captured the variety of physical findings observed in the clinical,
      surgical, or postmortem settings and transferred them to a permanent medium.
      Specifically, the study of human anatomy has enjoyed a historically popular
      courtship with medical artistry since 1543, when Andreas Vesalius published his
      now legendary work entitled De Humani Corporis Fabrica. However, the development
      and subsequent advancement of human anatomical illustration are indebted to
      individuals whose lifetimes span several centuries prior to Vesalius. The
      scientific achievements in anatomy manifest not only an advancement of knowledge,
      but also are a reflection of cultural, political, and religious beliefs. With
      respect to the development of human anatomic illustration, three elements were
      essential: the recognition of anatomy as a distinct branch of medical science,
      the acceptance of human dissection as a scientific method to advance
      understanding of anatomical structure, and the advancement in printing such that
      illustrations could be included alongside descriptive text. This brief study will
      examine these milestones while highlighting the origin of anatomical illustration
      in its historical context and its relationship to the development of human
      anatomy as a recognized medical science.

PMID- 10089039
TI  - The way ahead?

PMID- 10089040
TI  - Tomorrow's doctors: today's mistakes?
AB  - Tomorrow's Doctors, published by the General Medical Council of the UK in
      December 1993, has prompted far-reaching changes to medical education in Britain.
      We draw attention to some inconsistencies in the document and to those aspects of
      it that we maintain are undesirable. We question the emphasis in Tomorrow's
      Doctors on change in view of the unchanging nature of the structure and function
      of the human body. We doubt the wisdom of exhorting students to learn through
      curiosity and experiment, such methods being wasteful of time and resources when
      used in the context of accepted core material. We do not accept that the
      information overload is an automatic result of traditional methods of delivering
      education, and we are by no means convinced that the university model is the
      right one for medical education. In the face of experts being unable to agree on
      or to define scientific method, we wonder if consideration of this is appropriate
      in an undergraduate medical course, and we doubt that ethics and criticism are
      rightly placed in the undergraduate curriculum. The drawbacks of systems-based
      teaching are considered in the light of the disease process, and we draw
      attention to the lack of evidence for the document's condemnation of departmental
      structures and its uncritical espousal of integration. Finally, we consider some
      of the ways in which these changes have affected anatomy.

PMID- 10089041
TI  - Bilateral double axillary artery: embryological basis and clinical implications.
AB  - An unusual bilateral variation in the arterial pattern of the axilla was observed
      in an embalmed cadaver. Each axilla contained two axillary arteries of similar
      origins but different patterns of branching and fate. The first part of each
      axillary artery was a single vessel as is the norm. It gave off a supreme
      thoracic artery and then bifurcated into two medium-sized arteries hence referred
      to as regular and variant. The variant artery ran in an antero-medial course,
      partly covered by the one axillary vein. The regular artery gave off the
      thoracoacromial and two posterior branches from its second part, the anterior and
      posterior humeral circumflex arteries from its third part, and then continued as
      the brachial artery with all the usual branches except the profunda brachii on
      the right side. The variant gave off five arteries from the second part, a
      thoracoacromial artery, two separate long thoracic arteries each with a branch
      that ran along the intercostobrachial nerve to the arm, and two posterior
      branches. In the third part of the variant, the subscapular artery arose with its
      usual branches plus a common origin for two additional humeral circumflex
      arteries. The variant terminated as the profunda brachii artery to the right side
      while on the left side it terminated in muscular branches to the triceps. Hence,
      the arterial blood supply to the upper limb, and the axillary region in
      particular, was shared on both sides by two major arteries instead of one. These
      two arteries emanated from the first part of the axillary artery and may
      represent persisting branches of the capillary plexus of the developing limb
      buds. The findings have an embryological basis and clinical relevance considering
      the frequency of procedures in this region.

PMID- 10089042
TI  - Characteristics of the early phase of chronicity in acute hepatitis B infection.
AB  - The mechanism of development of chronicity after acute hepatitis B infection has
      not been elucidated fully. Following a single source outbreak of hepatitis B
      among 79 adult women, three patients (4%) became chronic carriers of hepatitis B
      virus (HBV). We compared features of the virus and antibody response of the
      latter three patients with those of 12 HBeAg-positive cases with resolving
      infection. The virus genotype was D, antigenic subtype ayw2. Base sequence
      analysis of S- and C-gene regions revealed no differences between the two groups.
      During the acute illness the three patients who developed chronicity had a
      remarkable transient reduction of HBsAg, HBeAg, and HBV DNA levels at 14-20 weeks
      after infection, the time of HBeAg seroconversion in the patients who cleared the
      infection. One HBeAg-specific monoclonal antibody (HBOT.95A) used as solid-phase
      antibody in a sandwich enzyme immunoassay detected an increased HBeAg signal in 2
      of the 3 patients that developed chronicity and in 1 of the 12 patients who
      recovered. The latter patient had an exceptional long period of HBsAg
      antigenemia. Standard HBeAg assays detected HBeAg in all cases. HBeAg and anti
      HBe-positive serum samples from the patients who recovered could inhibit the
      HBOT.95A response. The results suggest that chronic hepatitis B develops after an
      interruption of immune clearance. Differentiation of the antibody response to
      HBeAg may help to find patients with an increased risk for this interrupted
      immune clearance who might be candidates for an early intervention therapy.

PMID- 10089043
TI  - Detection of mutations in the enhancer 2/core promoter region of hepatitis B
      virus in patients with chronic hepatitis B virus infection: comparison with
      mutations in precore and core regions in relation to clinical status.
AB  - To investigate the meaning of the mutations in the enhancer 2/core promoter
      (Enh2/CP) region of hepatitis B virus (HBV) during the chronic HBV infection,
      mutations were examined in the Enh2/ CP region (carboxyl half of X region) and
      their correlation with mutations in the precore and core regions in relation to
      the presence of chronic liver disease. The entire nucleotide sequences of the
      Enh2/CP region were determined by direct sequencing of the amplified products
      derived from 30 cases with chronic HBV infection. The results were compared to
      the mutations in the precore and core regions. In the Enh2/CP region, 91
      generally scattered nucleotide substitutions were detected. There were 11
      substitutions in the 10 asymptomatic healthy carriers (mean, 1.1/case) and 80 in
      the 20 chronic liver disease patients (4.0/case). The most frequent substitutions
      from A to T at nucleotide 1764 and from G to A at nucleotide 1766 were seen in
      none of the 10 asymptomatic carriers and in 14 (70%) of the 20 chronic liver
      disease patients. Comparisons of mutations in the precore and core regions
      revealed that 14 of 16 patients with mutations in the core region had the
      mutations in the Enh2/CP region and/or a precore stop codon mutation. These data
      suggest that mutations in the Enh2/CP and precore regions may affect the
      expression of the core and HBeAg peptides and might be involved in the
      pathogenesis of chronic liver disease.

PMID- 10089044
TI  - Characterization of monoclonal antibodies against hepatitis C virus nonstructural
      protein 3: different antigenic determinants from human B cells.
AB  - The nonstructural (NS3) region protein of hepatitis C virus (HCV) possesses major
      B-cell epitopes that induce antibodies after infection. To elucidate further the
      characteristics of these B cells and their role in the immune regulation of HCV
      infection, T9 (portion of NS3 region, amino acids [a.a.] 1188-1493)-specific
      monoclonal antibodies were derived and mapped for B-cell antigenic determinants
      with recombinant proteins. A total of 10 T9-specific hybridomas were generated
      and tested for B-cell antigenic determinants. To analyze the B-cell antigenic
      determinants, eight recombinant proteins including NS3-e (a.a. 1175-1334), NS3-a'
      (a.a. 1175-1250), NS3-a (a.a. 1251-1334), NS3-b (a.a. 1323-1412), NS3-c (a.a.
      1407-1499), NS3-a/b (a.a. 1251-1412), NS3-bc (a.a. 1323-1499), and NS3-abc (a.a.
      1251-1499) encoded by NS3-region internal clones were expressed and tested for
      immunoblotting. The data suggested IgG hybridomas recognized NS3-a, NS3-a', or
      NS3-b protein by immunoblotting. By contrast, the NS3-e protein bears the major
      antigenic determinant recognized by human sera. Half of the hybridomas were found
      to react with protein NS3-a', which is not a major B-cell antigenic determinant
      in humans. These data suggested that conformational epitopes in vivo may be
      important for B-cell recognition.

PMID- 10089045
TI  - Ultracentrifugation and concentration of a large volume of serum for HCV RNA
      during treatment may predict sustained and relapse response in chronic HCV
      infection.
AB  - The ability to predict accurately a sustained response during therapy in patients
      with hepatitis C virus (HCV) infection is unavailable. The aim of this study was
      to differentiate, during therapy, patients who would relapse from those with a
      sustained response by ultracentrifugation for residual serum HCV RNA. Sixty-one
      specimens (from 32 patients) collected during interferon therapy were assessed by
      ultracentrifugation. All were negative using a quantitative polymerase chain
      reaction (PCR) (detection limit < or = 100 copies/ml). One-milliliter aliquots
      were ultracentrifuged at 23,000 x g (160 min), and then the nucleic acid pellet
      was extracted, precipitated, and resuspended. Qualitative PCR was carried out in
      quadruplicate using two separate 5'UTR primer sets (8 results/specimen). A
      specimen was positive if > or = 1 gels was positive compared to controls. At
      weeks 12 and 24, 9/9 (100%) sustained response patients were negative by
      ultracentrifugation. In the 23 relapse patients at week 12, 7/12 specimens were
      positive; at week 24, 7/14 were positive. Earlier time points could not
      differentiate the patients' eventual response to therapy. The predictive value of
      a positive ultracentrifugation test for relapse at week 12 or 24 was 100%. The
      predictive value of a negative test for sustained response was 62% and 50% at
      week 12 and 24, respectively. These preliminary results indicate that patients
      with an eventual sustained response will have no detectable serum HCV RNA by week
      12 or week 24. A positive result is 100% predictive of relapse.

PMID- 10089046
TI  - Identification of a novel variant of hepatitis E virus in Italy.
AB  - Hepatitis E infection is typically associated with areas in which hepatitis E
      virus (HEV) is endemic. Except for a few cases in Europe and in the United
      States, acute hepatitis E is usually associated with travel to endemic areas. We
      set out to determine the etiologic role of HEV in acute non-A-C hepatitis in
      Italy. The presence of HEV-RNA and antibody was determined in 218 patients
      diagnosed with acute viral non-A-C hepatitis. Acute hepatitis E infection was
      defined by the presence of HEV-RNA in sera and positivity for IgM anti-HEV and
      seroconversion to IgG anti-HEV. Acute hepatitis E was found in 10.1% of the
      patients with acute non-A-C, with 95.5% exhibiting a benign course. A more severe
      course was observed in a patient co-infected with HAV and HEV. Most cases were
      travelers to endemic areas, although 18.2% reported no travel. One patient was
      from a household with an infected patient. Sequence analyses of the polymerase
      chain reaction (PCR) product derived from a patient who never visited endemic
      areas, identified an isolate that is divergent significantly from all reported
      isolates of HEV (79.5-85.8% nucleotide identity). Evidence from this study
      suggests that HEV accounts for approximately 10% of acute non-A-C viral hepatitis
      in Italy, diagnosed generally in travelers returning from endemic areas. However,
      the identification of a new HEV variant in an individual who never indicated
      travel or contact with individuals associated with endemic areas, suggests that
      this virus may be native to Italy.

PMID- 10089047
TI  - Association of GB virus C (GBV-C)/hepatitis G virus (HGV) with haematological
      diseases of different malignant potential.
AB  - Among risk groups for GB virus C (GBV-C)/HGV infection, patients with
      haematological diseases are particularly exposed due to the combination of
      transfusional support and immunodeficiency status. To examine any association
      between GBV-C/HGV positivity and different malignancy potential of hematological
      diseases, we investigated two groups of patients, one with clonal stem cell
      disease with long latency period (myelodysplasia, myeloproliferative disease) and
      one with malignant haematological diseases (Hodgkin's lymphoma, non-Hodgkin's
      lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with
      the data from cytogenetic analysis at first diagnosis. The frequency of GBV-C/HGV
      infection in these patients was studied using reverse transcription-polymerase
      chain reaction (RT-PCR) and E2 antibody assay. Serum GBV-C RNA was found in 29/47
      (62%) patients. The prevalence of GBV-C RNA in the group of oncological cases
      (72%) was significantly higher (P= .02) than in the patients with clonal stem
      cell diseases (28%). Among the GBV-C negative cases, only 25% had malignant
      haematological diseases. The data from GBV-C/ HGV tested cases for which
      cytogenetic analysis was carried out indicated an association of GBV-C/HGV
      positivity with genomic destabilization in general. Of the cases with numerical
      and structural aberrations, 64% were GBV-C positive. A correlation could not be
      confirmed between GBV-C/HGV and liver enzyme levels, blood transfusions,
      chemotherapy treatment, or viral coinfection. These findings suggest a high risk
      of GBV-C/HGV infection in patients with haematological disorders especially in
      the group of malignant diseases. These observations may indicate that the
      persistence of GBV-C/HGV in these patients could be associated with
      susceptibility to genomic destabilisation.

PMID- 10089048
TI  - Influence of CD4+ lymphocyte counts on GB virus C/hepatitis G virus carriership
      in HIV-positive individuals.
AB  - The duration of the GB virus C or hepatitis G virus (GBV-C/HGV) carriership
      varies according to the patient group studied. The immune competence of the host
      may be important. GBV-C/ HGV was studied in human immunodeficiency virus (HIV)
      infected persons and an attempt was made to correlate the presence of viral RNA
      or E2 antibodies with CD4+ lymphocyte counts. Of 138 HIV-positive subjects, 30
      were GBV-C/HGV RNA-positive and 20 others were E2 antibody-positive, whereas in
      healthy GBV-C/HGV-infected persons, the proportion of E2 antibody carriers was
      much higher. On the other hand, a relationship was not found between CD4+
      lymphocyte counts and the presence of GBV-C/HGV RNA in the HIV-infected persons.
      This result does not necessarily imply that the CD4+ lymphocyte count does not
      affect viral clearance, but the results could be due to the trans-sectional
      nature of this study. A longitudinal assessment should clarify this point.

PMID- 10089049
TI  - Correlation of interferon treatment response with GBV-C/HGV genomic RNA and anti
      envelope 2 protein antibody.
AB  - The clinical significance of GB virus C/hepatitis G virus (GBV-C/HGV) co
      infection was studied retrospectively in 100 consecutive patients with hepatitis
      C virus (HCV) infection. All 100 patients had been treated with interferon-alpha
      (IFN-alpha). Co-infection with GBV-C/HGV and HCV was detected in 10 of the 100
      patients (10%) and anti-envelope 2 region (anti-E2) antibody was detected in 25
      patients. None of the patients with GBV-C/HGV RNA had anti-E2 antibody. Co
      infected patients were younger (P < .005) and their serum transaminase levels
      were lower than HCV-only infected patients (P< .01). In 7 of the 10 co-infected
      patients, HCV RNA was eradicated from serum after IFN-alpha treatment and normal
      alanine transaminase (ALT) levels continued in 6 of these 7 patients. In one
      patient who was negative for HCV RNA but positive for GBV-C/HGV RNA, the ALT
      level relapsed transiently. The rate of clearance of HCV and normalization of the
      ALT level was significantly higher in co-infected patients than in HCV-only
      infected patients (P < .05). GBV-C/HGV RNA disappeared from 6 of the 10 co
      infected patients (60%) upon cessation of IFN-alpha treatment. However,
      continuous clearance of GBV-C/HGV was observed in only two patients and anti-E2
      antibody could not be detected in the serum of these patients. These results
      indicate that co-infected patients tend to be younger and more sensitive to IFN
      alpha treatment. However, long-term clearance of GBV-C/HGV after IFN-alpha
      treatment may be difficult. Moreover, anti-E2 antibody may act to neutralize GBV
      C/ HGV.

PMID- 10089050
TI  - Amino acid substitutions in NS5A region of GB virus C and response to interferon
      therapy.
AB  - GB virus C (GBV-C) is related to hepatitis C virus (HCV) and has a similar
      genomic structure. Some predictors for the efficacy of interferon (IFN) therapy
      on HCV have been reported: genotype, viral load, IFN dose, and the amino acid
      substitutions in the NS5A region, designated as the interferon sensitivity
      determining region (ISDR). To evaluate the correlation between the amino acid
      substitutions in the GBV-C NS5A region and the response to IFN therapy, single
      strand conformation polymorphism (SSCP) analysis was performed in the 12
      concomitantly GBV-C-and HCV-infected patients who received IFN therapy at three
      time points: before, end-point, and after the IFN therapy. The region in the GBV
      C NS5A studied includes the amino acids that exhibit some homology to the ISDR
      and the various substitutions. By SSCP analysis, amplicons were separated into 1
      4 bands, which indicated the existence of heterogeneity in each host. However,
      the deduced amino acid sequences in these bands exhibited no characteristic
      differences among these strains irrespective of response to IFN therapy. Of the
      32 strains separated by SSCP, 7 strains were responders, and 25 were
      nonresponders. The mean amino acid substitution, compared with the consensus
      sequence of nonresponders, was 1.00+/-0.93 among responders, and 1.40+/-0.85
      among non-responders (P= NS). No correlation between the amino acid sequence in
      the GBV-C NS5A region and response to IFN therapy was found, indicating that the
      GBV-C NS5A region dose not act as the ISDR.

PMID- 10089051
TI  - High Epstein-Barr virus serum load and elevated titers of anti-ZEBRA antibodies
      in patients with EBV-harboring tumor cells of Hodgkin's disease.
AB  - Hodgkin's disease is commonly associated with EBV latent infection. The incidence
      of EBV reactivation (active infection or EBV infection with replicative cycle)
      was evaluated in a series of 30 patients with untreated Hodgkin's disease (except
      for one case with chronic lymphocytic leukemia) by quantitation of EBV DNA and
      titration of anti-ZEBRA antibodies in serum samples. DNA was detected in serum
      (>2.5 x 10(2) genomes/ml) in 15 of 30 patients and was more frequent in Hodgkin's
      disease with EBV-positive Reed-Sternberg cells (10/12) than in EBV-negative cases
      (5/18), (P< 0.01). Of interest was the demonstration that viremia correlated well
      with increased titers of anti-ZEBRA IgG and/or standard serological profiles of
      EBV reactivation (12/15), (P < 0.05). However the lack of EBV replicative cycle
      in Reed-Sternberg cells (negative for ZEBRA antigen and early antigen BHLF1)
      suggests that the viral replication occurs in a nonneoplastic cell compartment
      rather than in tumor cells. The measurement of EBV DNA loads and the titration of
      anti-ZEBRA antibodies shed new lights on the link between activation of EBV
      replication and Hodgkin's disease: these serological markers together with the
      determination of the EBV status of the tumor suggest that replication of the
      viral genome occurs with a decreased efficiency of the immune system, thus
      allowing progression of the tumor.

PMID- 10089052
TI  - Viral diarrhea in children in Beijing, China.
AB  - A study was undertaken from November 1994 to August 1996 to determine the role of
      viruses in children (< or =5 years of age) hospitalized at Beijing Children
      Hospital, Beijing China, for acute diarrhea. Stool samples from diarrheal
      patients were investigated by ELISA, electron microscopy, and RT-PCR for the
      presence of rotavirus, calicivirus, astrovirus, and adenovirus. Group A rotavirus
      was detected in 55.9% of all diarrheal patients and comprised 82.5% of all
      viruses detected. Group A rotavirus samples were further characterized for their
      G-type specificity by RT-PCR. Four major G types (1-4) were identified. G1 to G4
      accounted for 58.9%, 15.7%, 16.8%, and 6.3%, respectively, of the serotyped
      samples. Almost all rotavirus infections occurred in children less than 1 year of
      age, with a significant clustering during the winter months. Group C rotavirus
      was detected in one 18-month-old child. Astroviruses, caliciviruses, and
      adenoviruses were detected in 8.5%, 7.6%, and 2.5% of the hospitalized children,
      respectively. This, the first viral etiological study of childhood diarrhea in
      China, concludes that rotavirus G1-4 strains play an important role in severe
      diarrhea in Beijing children.

PMID- 10089053
TI  - Influence of the amino acid differences between the hemagglutinin HA1 domains of
      influenza virus H1N1 strains on their reaction with antibody.
AB  - For influenza H1N1 strains, including some of their escape variants, the
      association of amino acid differences located at their hemagglutinin HA1 domains
      with their antigenic relationship was examined. The antigenic relationship was
      recorded in terms of the ratios of hemagglutination inhibition (HI) titers, the
      concentration of antibody molecules recognized by the virus, and the equilibrium
      constant of epitope-paratope interaction determined with heterologous virus
      compared to that found with homologous virus. The HI titers of antisera were
      found to depend primarily on the concentration of antibody molecules recognized
      by the virus and much less on the equilibrium constants. The avidity of antibody
      in sera raised against historically later strains with earlier strains was higher
      than vice versa. In contrast to the results obtained with antisera, the same
      concentration of monoclonal antibody directed to the Sb site of A/Brazil virus
      was recognized by both heterologous and homologous viruses, and the differences
      in HI titers observed were due to avidity changes only. Some of the amino acid
      differences located at each of the antigenic sites were found to be associated
      with a reduction in the HI titers and in the concentration of antibody molecules
      recognized by heterologous virus, whereas other differences in addition decreased
      the avidity of epitope-paratope interaction. Further amino acid differences
      decreased the avidity only. The strains tested differed also in their amino acids
      located outside the antigenic sites. However, an influence of these differences
      on the reaction of virus with antibody could not be evidenced. For the strains
      tested, the antigenic hemagglutinin drift occurred by reduction of the
      concentration of antibody molecules recognized by the virus and by avidity
      changes, which, in turn, were caused by exchanges of some key residues located at
      the antigenic sites.

PMID- 10089054
TI  - Detection rates of TT virus among children who visited a general hospital in
      Japan.
AB  - Recently, genomic DNA of the novel TT virus (TTV) was isolated from patients
      suffering from posttransfusion hepatitis of unknown etiology. We examined sera
      from 197 children who visited the Department of Pediatrics at Toyohashi National
      Hospital. Sera were tested for TTV DNA by seminested polymerase chain reaction
      (PCR) using a set of primers synthesized according to the published TTV sequence.
      Ten children were found to be positive for TTV (5.1%). All positive PCR products
      were directly sequenced in both directions using a fluorescent dye terminator
      cycle sequencing system. The sequences were compared by a multiple sequence
      alignment and a phylogenetic tree was constructed. The phylogenetic tree showed
      that two of the TTV isolates found in the present experiment did not belong to
      any of the phylogenetic groups previously reported.

PMID- 10089055
TI  - Insulinoma/hypoglycemic syndrome: a statistical evaluation of 1085 reported cases
      of a Japanese series.
AB  - Over the past 25 years and more, very few statistically reliable evaluations
      dealing with clinicopathologic features of patients with insulinoma and/or
      hypoglycemic syndrome (HGS), including recently popularized diagnostic
      modalities, have been published. The aims of this study are threefold: first, to
      evaluate the clinicopathologic features of patients with insulinoma/HGS from
      various viewpoints; secondly, to update our knowledge about this subject which
      has been retained up to date, and thirdly to supply reliable information to
      investigators working in the specialized field of gut-pancreatic endocrinomas. We
      collected data from literature on a total of 1085 Japanese patients with
      insulinoma/HGS and undertook a statistical evaluation. The results are summarized
      as follows. 1) Association of HGS was recognized in 88.4% of the 1085 patients.
      2) Islet B-cell hyperplasia/nesidioblatosis was found in 4.1%; 2.6% in
      association with insulinoma and 1.6% without it. 3) Patients with small tumors of
      20 mm or less comprised 81.1%. 4) The overall rate of metastases was 6.6% (72
      patients) and that of malignancy 13.6% (148 patients). 5) Multisecretors
      immunohistochemically proved were found in 32.4% and multiplicity of tumor growth
      in 12.6%. 6) The 10-year survival rate after removal of lesions was 90.5%
      overall; 98.4% in patients with benign lesions and 75.7% in those with malignant
      tumors. It is expected that the results obtained in the present study will
      provide extensive and useful information for future investigation.

PMID- 10089056
TI  - Vipoma/diarrheogenic syndrome: a statistical evaluation of 241 reported cases.
AB  - Based on a statistically reliable number of cases reported in international
      literature, this study aimed to analyze the present status of
      vipoma/diarrheogenic syndrome (DGS). Another purpose was to supply investigators
      in the field of pancreatic endocrinology with precise and extensive information
      for the future analysis and evaluation of this subject and related problems. We
      obtained a total of 241 patients with vipoma/DGS from the international
      literature of 179 with intrapancreatic vipomas, 48 with extrapancreatic
      neurogenic tumors such as ganglioneuroblastomas, ganglioneuromas and
      neuroblastomas, and 14 with extrapancreatic vipomas of non-neurogenic nature.
      When data were considered adequate, a comparative study was attempted between the
      two groups. A statistically significant difference between the two groups with
      pancreatic vipomas and neurogenic tumors was found in the rate of the associated
      syndrome (84.4% versus 95.8%: averaging 86.3%), in tumors the size of which was
      over 20 mm (79.1% versus 100.0%), in the metastases (56.4% versus 29.2%) and rate
      of malignancy (64.8% versus 33.3%), and in the rate of resection of primary
      lesions (68.7% versus 87.5%). When compared to nodal metastasis, hepatic
      involvement was significantly more frequent in the pancreatic vipoma group (4.2%
      versus 20.8%). Recent trials of adjuvant chemotherapy with somatostatin analogues
      indicates an effective result of 78.4% exceeding 31.0% when treated with
      streptozotocin. The 5-year survival rate in 89 effective patients with pancreatic
      vipomas was 68.5%; 59.6% for 43 of the patients with metastases and 94.4% for 46
      of the patients without metastases.

PMID- 10089057
TI  - Nucleotide fractional incorporation: a simple metabolic feature potentially
      related to clinical outcome in colorectal cancer patients.
AB  - Among the different investigated biomarkers, cell proliferation has provided
      valuable information on the clinical outcome of patients with malignant tumors.
      In the present study, we analyzed the potential relevance of fractional
      incorporation (FI) of a nucleotide precursor (3H-thymidine, 3H-dT) into DNA of
      tumor cells, determined on the primary tumor, on long-term clinical outcome of a
      series of patients with colorectal cancer. Determination of 3H-dT FI was carried
      out on fresh tumor material obtained at surgery as part of the clinical
      management of the primary tumor in 28 patients with colorectal cancer. Analysis
      of the relation between the FI and clinico-pathological characteristics of the
      tumor showed a trend of an inverse relation between the biomarker and Dukes'
      stage and no relation with tumor site. At 6 year follow-up, alive patients had a
      statistically significant higher median FI value (2.4%; range: 1.1-6.5%) than
      dead patients (1%; range: 0.3-4.5%) (p=0.02). Owing to the simplicity of this
      inexpensive methodology, the preliminary results of our study would indicate the
      potential of FI, a metabolic-kinetic parameter, to give prognostic information in
      colorectal cancer patients.

PMID- 10089058
TI  - Leiomyosarcomatosis involving the duodenum and the subcutaneous tissue.
AB  - Soft tissue sarcomas include only 0.7% of all malignancies and leiomyosarcomas
      constitute about 10% of all sarcomas. Very rarely leiomyosarcoma may present as
      multifocal primaries. We report a 65-year-old patient with multiple subcutaneous
      nodules. During the investigation period the patient had hematemesis and melena.
      Upper gastro-intestinal endoscopy was performed and multiple polipoid lesions
      were discovered in the duodenum. The rest of gastrointestinal system was normal
      with barium graphies. Biopsies from the subcutaneous nodules and duodenal lesions
      showed leiomyosarcoma. Although we cannot rule out the possibility of metastases,
      we strongly consider a multicentric origin since no other metastasis is present
      and duodenal lesions are also multiple.

PMID- 10089059
TI  - Germinal cell tumors of the testis in cryptorchids.
AB  - The medical records of 876 patients with germinal cell tumor of the testis seen
      at our hospital between 1984 and 1996 were analyzed; 25 (2.85%) were reported to
      have tumors in undescended testis. Twenty-one patients had unilateral involvement
      and four had bilateral. Cryptorchidism was corrected ipsilaterally in 7 patients
      with intrascrotal testicular cancer between 6 and 13 years of age. The primary
      tumor was in the abdominal testis in 11 patients and in the inguinal canal in 7
      (28%) patients. Three patients had persistent Mullerian duct syndrome. One of the
      three patients with persistent Mullerian duct syndrome also had transverse
      testicular ectopia. Clinical staging showed 10 stage I, 8 stage IIC, 3 stage III
      and 4 stage IV. Tumor histologic types on orchidectomy showed seminoma in 20, non
      seminoma in 3 and mixed tumors in 2 patients. According to stage and histologic
      findings all patients were treated with radiotherapy or chemotherapy. Overall, 3
      and 5 years survival in seminoma patients was 100% while in non-seminoma and
      mixed tumor patients was 80% and 60%, respectively. Since orchidopexy offers only
      limited protection against future malignancy if performed after 2 years of age,
      the treatment of choice should be orchidectomy. Cryptorchid testes that descended
      spontaneously or by hormonal therapy should be followed lifelong by testicular
      ultrasound at least once a year for early detection of cancer. For bilaterally
      orchidectomised cases administration of androgens is mandatory to prevent sexual
      dysfunction and hot flushes.

PMID- 10089060
TI  - Serum concentrations of proinflammatory cytokines in advanced non small cell lung
      cancer patients.
AB  - To assess the relationship between serum concentrations of proinflammatory
      cytokines and prognosis of non small cell lung cancer (NSCLC), we evaluated the
      serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1
      beta) and interleukin-6 (IL-6) in 60 patients with untreated advanced NSCLC. Mean
      cytokines concentrations in patients were significantly higher than in the
      control population. Patients with metastatic disease had higher levels than those
      with undisseminated disease. Finally, in patients with tumor progression we
      observed an increase of cytokines serum levels. These results suggest that in
      NSCLC elevated serum levels of proinflammatory cytokines may have prognostic
      value being associated with a worse prognosis.

PMID- 10089061
TI  - Influence of alpha-tocopherol and ascorbic acid on pan masala induced genomic
      damage. An in vitro experiment.
AB  - Pan masala is a dry complex mixture of areca nut, catechu, lime, cardamon,
      unspecified flavouring agents etc., with (PMT) or without tobacco (pm). We have
      previously reported genotoxic potential of tobacco, areca nut and pan masala per
      se. An antigenotoxic effect of alpha-tocopherol (AT) and ascorbic acid (AA)
      against the PM/PMT induced genotoxic on Chinese hamster ovary (CHO) cells have
      been studied using chromosone aberration (CA) assay. AT and AA, per se, had no
      effect on CA frequency at the concentrations used in the present study. The short
      term treatment of AT with aqueous extracts of PM/PMT yielded lower frequencies of
      CA as compared to the cultures treated with aqueous extracts of PM/PMT alone.
      However, a statistically significant reduction in CA frequency was observed with
      continuous treatment only. AA had no statistically significant protective effect
      except for continuous treatment with 10 ug/ml AA against the aqueous extract of
      PMT. The results indicate the possible use of AT to reduce the risk of oral
      cancer among PM/PMT chewers.

PMID- 10089062
TI  - Prognostic significance of tumor DNA content in carcinoma of the hepatic duct
      confluence.
AB  - Carcinoma of hepatic duct confluence was characterized by Klatskin, as a small,
      relatively slow-growing and sharply localized tumor. Sixty consecutive patients
      with carcinoma of the hepatic duct confluence were surgically resected in our
      Department between January 1984 and December 1996. All histological section of
      each patient included in the study were reviewed. The nuclear content was
      measured. Twenty-nine patient (48%) had diploid tumors and 31 (51%) were found to
      have aneuploid tumors. Survival of patients with a diploid tumor was
      significantly longer than those with aneuploid tumors. Our results indicate that
      DNA ploidy is an important, prognostic factor of carcinoma of the hepatic duct
      confluence.

PMID- 10089063
TI  - Protective effect of curcumin, ellagic acid and bixin on radiation induced
      genotoxicity.
AB  - Induction of micronuclei and chromosomal aberrations produced by whole body
      exposure of r-radiation (1.5-3.0 Gy) in mice was found to be significantly
      inhibited by oral administration of natural antioxidants, curcumin (400 micro
      moles), ellagic acid (200 micro moles) and bixin (200 micro moles) per kilogram
      body weight. These antioxidants induced inhibition of micronucleated
      polychromatic and normochromatic erythrocytes, was comparable with alpha
      tocopherol (200 micro moles) administration. Curcumin and ellagic acid were also
      found to significantly reduce the number of bone marrow cells with chromosomal
      aberrations and chromosomal fragments as effectively as alpha-tocopherol.
      Moreover, administration of antioxidants inhibited the DNA strand breaks produced
      in rat lymphocytes upon radiation as seen from the DNA unwinding studies. These
      results indicated that antioxidant curcumin, ellagic acid and bixin provide
      protection against chromosome damage produced by radiation.

PMID- 10089064
TI  - Aclarubicin inhibits etoposide induced apoptosis through inhibition of RNA
      synthesis in P388 murine leukemic cells.
AB  - It has been reported that aclarubicin inhibits etoposide (VP-16) induced
      cytotoxicity in human lung cancer cell lines (1, 2). However, it still remains
      unclear how aclarubicin (ACR) inhibits etoposide-induced cytotoxicity. We report
      here that the combination of ACR and VP-16 showed antagonistic cytotoxic effect
      in P388 murine leukemic cells. DNA unwinding assay showed that 1000 ng/ml ACR
      significantly reduced VP-16 induced early DNA double strand(ds) breaks compared
      to that of VP-16 alone at a concentration of 10 microM. However, ACR did not
      inhibit VP-16 induced early DNA double strand breaks at a concentration of 100
      ng/ml, a clinically achievable concentration. Furthermore, DNA repair occurred
      within two hours after removing VP-16 even if ACR was co-cultured at
      concentrations of 100 and 1000 ng/ml. DNA agarose gel electrophoresis and
      detection of sub-G1 fraction by flowcytometer showed that 100 ng/ml of ACR
      inhibited VP-16 induced DNA ladder formation and formation of sub-G1 fraction.
      Radioactive precursor incorporation studies showed that VP-16 inhibited DNA
      synthesis rather than RNA synthesis. On the other hand, ACR selectively inhibited
      RNA synthesis at a concentration of 100 ng/ml. The VP-16 induced increment of
      [3H]-L-leucine uptake was canceled by addition of 100 ng/ml of ACR. These data
      suggest that ACR inhibited VP-16 induced apoptosis by the inhibition of RNA
      synthesis along with protein synthesis, but not early DNA double strand breaks
      and DNA repair at a concentration of 100 ng/ml in P388 murine leukemic cells.

PMID- 10089065
TI  - A complex translocation involving chromosomes 2, 9 and 22 in a patient with
      chronic myeloid leukemia.
AB  - A patient with a high leukocyte count, diagnosed with chronic myeloid leukemia
      was referred for cytogenetic study. Peripheral blood and bone marrow cells were
      cultured without mitogenic stimulation. All karyotypes represented rare, varient
      Philadelphia chromosome with-three way translocation, i.e. t (2; 9; 22) (p13;
      q34; q11).

PMID- 10089066
TI  - Interleukins, TNF-alpha and beta-2M in patients with B cell chronic lymphocytic
      leukemia.
AB  - In order to investigate the possible existence of a prognostic factor for B cell
      chronic lymphocytic leukemia (B-CLL), we determined the serum levels of TNF
      alpha, IL-1a, IL-1b, IL-2, sIL-2R, IL-6, IL-10 and beta-2M in 20 patients. We
      observed significant changes in sIL-2R and beta-2M levels, whereas in all stages
      of disease, TNF-alpha and other interleukins exhibited only mild changes. An
      excellent correlation between sIL-2R and beta-2M levels and disease activity wes
      reported. Patients with aggressive disease (Rai stages III and IV and Richter's
      syndrome) had increased levels. Patients who responded to therapy and with
      improved clinical status had decreased sIL-2R and beta-2M levels. However,
      patients with progressive disease and no response to therapy were associated with
      increased levels of sIL-2R and beta-2M. In conclusions, as serum levels of sIL-2R
      and beta-2M are increased in the aggressive stages of B-CLL, they may be used as
      reliable markers for monitoring B-CLL activity, showing response to treatment and
      early relapse and/or disease progression.

PMID- 10089067
TI  - Transient increase of plasma interleukin-6 after infusion of recombinant tumor
      necrosis factor alpha in advanced cancer patients.
AB  - Tumor Necrosis Factor alpha administered in the therapy of advanced cancer
      influences certain hormones and cytokines secretion. In turn, these also modulate
      the biological activity of Tumor Necrosis Factor alpha. It has been shown in
      several studies that the cytokine Interleukin -6 (IL)-6 is produced in response
      to various hormones and other cytokines eg. Tumor Necrosis Factor (TNF alpha). In
      our study we focused on the Interleukin-6 (IL-6) secretion in response to TNF
      alpha administration in 12 patients undergoing TNF alpha biotherapy due to
      advanced neoplastic disease. Plasma IL-6 was estimated prior and at various time
      points (2, 3, 5 a,d 12 hours) after TNF alpha intravenous infusion. IL-6 level
      was estimated with ELISA method. In conclusion, we suggest the stimulating
      influence of hrec TNF alpha administered as therapy for advanced cancer on IL-6
      secretion.

PMID- 10089068
TI  - Mucocutaneous paraneoplastic syndromes (MCPS). A clinical-pathologic review.
AB  - Mucocutaneous paraneoplastic syndromes (MCPS) are a common group of dermatoses
      exhibiting a variable morphologic and pathologic picture which can occur in
      association with solid tumors or hematologic malignancies. In this review the
      Authors report the most important clinical characteristics and commonly
      associated malignancies of these dermatoses. Their identification is important
      because their superficial appearance and precocious arising are useful in the
      early diagnosis of an otherwise asymptomatic visceral malignancy and because
      differential diagnosis between skin metastases and malignancy-associated
      dermatoses is very important for a careful staging and management of the
      neoplasm. At the same time, MCPS may also be suggestive of the specific type of
      cancer present. Finally, the presence of a MCPS often carries grave oncologic
      implications. Once, therefore, the diagnosis of these dermatoses has been
      established, either an appropriate evaluation for an asymptomatic neoplasm in a
      cancer-free individual or an investigation for the recurrence of malignancy in an
      oncologic patient should be initiated.

PMID- 10089069
TI  - Effect of pirarubicin for elderly patients with malignant lymphoma.
AB  - To determine the effect of a chemotherapy regimen containing pirarubicin, a
      multicenter clinical trial was performed in naive patients > or = 65 years with
      malignant lymphoma, between January 1990 and December 1992. The total number of
      patients was 37 (median age 74.2 years). One of three different types of
      chemotherapy regimens, which was administered every 3 to 5 weeks, was chosen for
      each patient at random. Regimen A (THP-COP) included pirarubicin (30 mg/m2; day
      1), cyclophosphamide (500 mg/m2; day 1), vincristine (1 mg/m2; day 1) and
      prednisolone (30 mg/m2; days 1-5), regimen B, modified "CHOP", included
      doxorubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1) vincristine (1
      mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5); regimen C (THP-COPE)
      included etoposide (80 mg/m2; day 1) in addition to regimen A. The complete
      response (CR) rate was 60.0%, 45.5% and 62.5% with regimen A, B and C. The
      partial response (PR) rate with regimen A was 20.0%, 18.2% with B and 25.0% with
      C. The 50% survival period with regimen A was more than 1,000 days, with C 643
      days but it was only 365 days with B. The adverse effects related to these
      treatments occurred more frequently in regimen B than A and C showing a
      statistically significant difference. We concluded that chemotherapy regimens
      containing pirarubicin are useful and safe for the elderly patients with
      malignant lymphoma.

PMID- 10089070
TI  - Impact of tumor stage, operative down-staging, tumor grade and
      radioresponsitivity of the tumor on survival in supratentorial astrocytomas.
AB  - This retrospective study analyzed specifically the predicting factors for
      radioresponse and survival in 74 supratentorial astrocytoma patients. As a result
      of this study, cytoreduction in terms of ODs to T1 or T0 stage level or pre-RT T1
      tumor stage along with radioresponse has a positive impact on long-term survival.
      It seems that radical radiotherapy should be the choice of treatment for the
      patients who had pre-RT T0 and T1 disease who were found more likely to respond
      to radiotherapy. This has not been reported previously and needs to be confirmed
      in larger trials.

PMID- 10089071
TI  - Epilepsy and gliomas: incidence and treatment in 119 patients.
AB  - One hundred and nineteen consecutive patients affected by supratentorial gliomas
      were studied in order to determine the incidence of seizure at diagnosis, the
      occurrence of subsequent seizures and the efficacy of anticonvulsant treatment.
      The overall incidence of seizures as presentation symptom was 52% (62 patients).
      Preoperative seizures were present in 83% of patients affected by low-grade
      astrocytoma, in 46% of patients affected by anaplastic astrocytoma and in 36% of
      patients affected by glioblastoma. Postoperative epilepsy refractory to
      anticonvulsant treatment significantly related to low-grade histology and
      presence of preoperative seizures occurred in 48% of patients. Adverse effects
      associated with anticonvulsants were observed in 33.8% of patients treated with
      phenobarbital, 14.3% in the group treated with carbamazepine and 12% of patients
      treated with vigabatrin. We conclude that anticonvulsant treatment in patients
      affected by gliomas is often ineffective and prophylactic treatment should be
      discontinued after 6 months in patients preoperative seizures free. In patients
      with high risk of seizures antiepileptic drugs with good efficacy and lower
      incidence of adverse effects than phenobarbital are indicated.

PMID- 10089072
TI  - Tumor characteristics involved in the metastatic behaviour as an improvement in
      primary cutaneous melanoma prognostics.
AB  - We report the results of a retrospective immunohistochemical study on routinely
      fixed, paraffin embedded tissues from 147 primary cutaneous melanomas belonging
      to the classes pT3 and pT4, the development of which has been followed for at
      least five years. The parameters Cathepsin B, Cathepsin D, Collagenase IV,
      Metallothionein and PCNA were selected from previous studies on small
      collectives. All parameters showed statistically significant differences between
      tumors of the metastatic and the nonmetastatic group. Particularly conspicuous
      was the expression of Cathepsin B, Cathepsin D and Collagenase IV at the dermal
      invading front of the tumors. Based on this data we present a procedure of
      combining these data with established clinical-histological parameters such as
      tumor thickness and ulceration to an integrated individual risk factor that
      improves the certainty of melanoma prognosis.

PMID- 10089073
TI  - Quantitative analysis of the cyclin expression in human esophageal cancer cell
      lines.
AB  - To study the altered mechanisms of cell cycle regulation in esophageal cancer,
      the expressions of cyclins involved in G1/S transition were analyzed in a series
      of 26 human esophageal cancer cell lines. To evaluate and compare the levels of
      cyclin expression, flow cytometric analysis was performed using human lymphocytes
      as control. Increased expressions of cyclin A, D1, D3 and E were found in 23.1%
      (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines,
      respectively. All cell lines studied expressed less cyclin D2 than lymphocytes
      and the majority of the cell lines expressed cyclin D3 at levels similar to those
      of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E.
      Expressions of cyclin D1 and E were significantly elevated as compared to those
      of cyclin A, D2 and D3. These results suggest that increased expressions of the
      positive cell cycle regulators cyclin D1 and E may play an important role in
      esophageal carcinogenesis.

PMID- 10089074
TI  - Germline mutations of the p53 gene in children with malignant solid tumors.
AB  - Although somatic mutations of p53 are the most common genetic changes observed to
      date, the frequency of germline p53 mutations is found to be very low in sporadic
      malignant tumors. It has been postulated that de novo germline p53 mutations may
      occur in a substantial population of patients in pediatric age group, who die of
      their disease and do not propagate the mutation. To determine the frequency and
      type of p53 germline mutations in pediatric patients, we screened 65 children who
      were consecutively admitted with primary malignant solid tumors.

PMID- 10089075
TI  - The expression of the proliferating antigen Ki67, PCNA and products of suppressor
      gene p53 in primary invasive ductal breast carcinoma.
AB  - The classification of histological malignancy by Bloom and Richardson used in
      ductal invasive breast cancer seems to be not sufficient. In the same group of
      patients with the same clinical status as well as pathological malignancy the
      prognosis can be different and unpredictable. The aim of the study was to examine
      a consecutive series of primary ductal invasive tumours to find out: a) the
      expression of some biological cellular parameters as proliferating antigens Ki67
      and PCNA and the products of the suppressor gene p53; b) the correlation between
      the levels of expression of those factors and classical prognostic factors, such
      as tumour diameter, status of axillary lymph nodes, status of steroids receptors,
      degree of histological differentiation. It seems that the estimation of
      proliferating antigens together with products of suppressor gene p53 might have
      greater prognostic value than the estimation of single factors.

PMID- 10089076
TI  - Poly(A)polymerase activity levels in breast tumour cytosols.
AB  - The enzyme poly(A) polymerase (PAP) catalyses the polyadenylation of mRNA and its
      activity levels vary within the cell cycle. The levels of activity of this enzyme
      were measured in the cytosol of breast tumours from 62 untreated patients and
      compared to clinical prognostic parameters as well as other biological markers.
      The enzyme levels measured ranged from 3 to 46 units/mg protein. A statistically
      significant association was observed between high PAP activity values and the TNM
      stage of the disease as well as node invasiveness. Furthermore, there was a
      positive correlation between PAP activity values and c-erbB-2 overexpression but
      not with its amplification. No significant correlation was observed with c-myc
      amplification or overexpression and cathepsin D levels. A direct relationship
      between steroid receptor content and PAP activity levels, which was more
      prominent in the case of the progesterone receptor, was observed. However, also
      on the basis of previous data PAP activity may prove to be indicative of
      aggressive disease. Furthermore, measurements of PAP activity may contribute to
      the definition of the biological profile of tumour cells.

PMID- 10089077
TI  - Mammary Paget's disease with acantholytic features and without any detectable
      breast tumor.
AB  - Paget's disease is usually associated with an underlying adenocarcinoma of the
      breast. The initial manifestation is an eczematous or psoriasiform lesion of the
      nipple, soon extending to the mammary areola and then to the surrounding skin.
      The histology of the lesions is characterized by the presence, within the
      epidermal layer, of the so-called Paget's cells, i.e. large cells with vesicular
      nucleus and clear cytoplasm. The authors report a recent case of Paget's disease
      of the breast in a 75-year-old woman, unusual both for clinical course and
      observed histology. As for the clinico-evolutive aspects, although in the case
      observed the initial skin lesions appeared 20 years before, the different
      diagnostic procedures repeatedly performed showed no evidence in this patient of
      an underlying adenocarcinoma. The histologic aspect, on the other hand, was
      peculiar since the typical characteristics of an acantholytic disease were
      evident. The presence of intraepidermal cleavages with lost, at times, of the
      normal contacts among the cells of the Malpighian layer has been described only
      once in Paget's disease. This fact caused some diagnostic difficulties: however,
      the typical finding of the Paget cells, their positivity to histochemical methods
      such as cytokeratin and acid phosphatase allowed the diagnosis. The authors, at
      last, evaluate the need of a surgical therapy in Paget's disease of the breast
      without an underlying adenocarcinoma.

PMID- 10089078
TI  - Tall cell variant of papillary thyroid cancer.
AB  - Papillary histologic type is the most common form of thyroid carcinoma amounting
      to 85% cases. This pathology presents a rather good prognosis, but a few years
      ago, new subtypes have been described. Some of these variants show a fairly good
      prognosis i.e follicular, macropapillary, encapsulated while others appear to
      have a decidedly worse one, columnar cells, diffused sclerosing, or even to be
      clearly malignant as in the case of the tall cell variant. The authors report a
      case treated by a combined surgical and radiometabolic therapy and evidence the
      main characteristics of this rare and underestimated neoplasia.

PMID- 10089079
TI  - Cell cycle synchronization of FRTL5 cells. A physiological model system.
AB  - We describe a "physiological" cell cycle synchronization model system. FRTL5
      cells, TSH-dependent for proliferation, were starved from TSH. The cell cycle
      phases and the expression of markers associated to different cycle phases were
      evaluated. TSH starvation blocks proliferation without provoking death and
      induces virtually all the cells to accumulate in G0/G1 phase. TSH readdition
      allows 30% of these cells to enter the S phase. DNA topoisomerase II 170-kDa
      isoform is not expressed in G0/G1 synchronized cells while it is expressed in
      logarithmic growing cells. The 180-kDa isoform is not expressed in G0/G1
      synchronized cells while it is expressed in 20% of logarithmic growing cells
      regardless of the cycle phase. c-myc mRNA is not expressed in G0/G1 synchronized
      cells while it is detectable upon TSH readdition. This system provides a tool for
      the analysis of events associated with the G0/G1 phase and the transition from
      G0/G1 to S phase.

PMID- 10089080
TI  - Neuroendocrine differentiation in follicle-cell thyroid carcinoma: correlation to
      prognostic factors in papillary carcinoma.
AB  - The presence of NE-differentiation in the follicle-cell thyroid carcinoma has
      been investigated by immunohistochemical detection of chromogranin A in the
      neoplastic cells. It has been found that NE-differentiation was present in a
      significant percentage in the papillary Ca alone (46.60%) whereas all Huerthle
      cell neoplasms and the large majority of follicular and undifferentiated
      carcinomas showed non reactivity for Chromogranin A. Moreover, we have correlated
      the presence of NE-differentiation to well known prognostic factors in papillary
      Ca. We found a statistically significant correlation between the neuroendocrine
      differentiation and some unfavourable factors such as old age of the patient,
      size of the tumor, invasion of thyroid capsule and lymphnode involvement. We
      suggested that NE-differentiation could be considered as an index of poor
      prognosis.

PMID- 10089081
TI  - How about trying even harder...?

PMID- 10089082
TI  - An interview with Professor P. Guex of the Service de Psychiatrie de Liaison in
      Lausanne. Interview by F. Stiefel.

PMID- 10089083
TI  - The development for the Japanese Society for Palliative Medicine.
AB  - The early days of the hospice movement in Japan are described and developments
      traced up to the present day.

PMID- 10089084
TI  - Assessment of the quality of life of patients with advanced and end-stage cancer
      or serious infections with a symptom-based or an impact-based instrument.
AB  - In 1992 a project was started in which home care technology was made available to
      patients with cancer or serious infections. Primary care providers were trained
      and supported to administer parenteral drugs and fluids in the home setting.
      Between 1992 and 1995 we applied the Rotterdam Symptom Checklist (RSCL) and the
      Sickness Impact Profile (SIP) as questionnaires for quality of life (QoL)
      assessment in a group of 112 hospitalized patients who were prepared to receive
      further treatment at home. Scores on the RSCL revealed a high level of
      symptomatology in both the physical and the psychological dimension. Factor
      analysis showed a five-factor rather than a two-factor structure. The SIP showed
      considerable restrictions in daily living, particularly in the physical
      dimension. Whereas the RSCL and the SIP correlated well in the psychological and
      physical dimensions in advanced cancer patients, this correlation disappeared in
      the group of endstage cancer patients. The data indicate that the health-related
      QoL of end-stage cancer patients cannot be reliably be assessed with a symptom
      based instrument alone; it needs to be supplemented by other instruments, such as
      the SIP.

PMID- 10089085
TI  - Current practices for management of oral mucositis in cancer patients.
AB  - Many anticancer therapies induce oral mucositis, diminishing the patient's
      quality of life. Especially in neutropenic patients, it can lead to life
      threatening systemic infection. Moreover, it can become a limiting factor in
      intensive treatment schedules. Many interventions are aimed at reducing trauma
      and the risk of secondary infection. The institution of good oral hygiene seems
      to play a crucial part and can be achieved manually or by means of antiseptic
      agents. More specific antimicrobial therapy may be indicated. In addition, local
      and/or systemic pain control may be required. The administration of hematological
      growth factors, cryoprotectants and other agents or measures that may be of help
      in the management of mucositis are discussed.

PMID- 10089086
TI  - Social interaction and support related to mood and locus of control in cervical
      and endometrial cancer patients and their spouses.
AB  - The purpose of the study was to investigate possible relationships between
      quantitative and qualitative social support measures and mood in cervical (n =
      30) and endometrial (n = 30) cancer patients and their spouses before and after
      treatment. Furthermore, the experience of locus of control was studied in light
      of mood and social support in women after treatment. The first interview with the
      patients was conducted on the day before the women started treatment, a second
      interview, 6 months later and a third one, 12-15 months after the initiation of
      treatment. The interviews with the spouses were conducted on the telephone before
      the initiation of their partners' treatment and 12-15 months later. Social
      support was assessed by the Interview Schedule for Social Interaction (ISSI), the
      Beck Depression Inventory (BDI) was used to measure the level of depressive
      symptomatology, and the locus of control orientation was assessed by the Locus of
      Control (LOC) scale. Women with cervical cancer reported BDI values that were
      significantly higher than in the endometrial group both before and after
      treatment. Women with cervical cancer also showed a significantly higher level on
      the BDI score on both occasions than did the corresponding group of spouses. The
      scores for ISSI were within normal limits in both groups of women. Furthermore,
      LOC was significantly correlated with adequacy of social interaction in women
      when controlled for social desirability, whereas LOC was unrelated to BDI. No
      significant correlations were found among the spouses concerning social network
      variables and dysphoric mood. The necessity of developing models for the
      psychological and behavioural risk assessment and for the elaboration of adequate
      treatment strategies is emphasized.

PMID- 10089087
TI  - The anti-emetic efficacy of tropisetron plus dexamethasone in patients treated
      with high-dose chemotherapy and stem cell transplantation.
AB  - Among the most distressing symptoms experienced by patients who have undergone
      high-dose chemotherapy and stem cell transplantation are nausea and vomiting. The
      chemotherapy regimens used in high-dose conditioning protocols are highly
      emetogenic. The 5HT3 receptor antagonists are very effective in the prevention
      and abolition of nausea and vomiting resulting from chemotherapeutic drugs. One
      of them, tropisetron, is a selective antagonist of serotonin 5HT3 receptors with
      proven efficacy against emesis. Dexamethasone is also known as an effective agent
      against nausea and vomiting. The addition of dexamethasone to a 5HT3 receptor
      antagonist is synergistic, as has been shown in many trials with highly
      emetogenic drugs. The aim of the present trial was to study the efficacy and
      safety profile of the combination of tropisetron and dexamethasone in controlling
      nausea and vomiting in patients receiving megatherapy prior to stem cell
      transplantation. We studied 31 patients. All of them were evaluable for response
      and toxicity. The majority of patients achieved complete or major protection
      against acute vomiting (71-83%), and 67-84% of the patients had no or mild
      nausea. The combination was tolerated well, and only a minority of patients
      reported side effects. Among them the most common were headache (in three
      patients) and constipation. No patient withdrew from the study because of
      toxicity. It has become evident from our data that the administration of 5 mg
      tropisetron daily in combination with 20 mg dexamethasone for 8 days can prevent
      the acute emesis otherwise experienced by patients receiving high-dose
      chemotherapy as conditioning in stem cell transplantation programmes.

PMID- 10089088
TI  - Nausea and vomiting induced by arterial chemo-embolization in patients with
      hepatocellular carcinoma and the antiemetic effect of ondansetron hydrochloride.
AB  - To determine the incidence of nausea and vomiting and the antiemetic effect of
      ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated
      with arterial chemo-embolization, we studied 59 patients with hepatocellular
      carcinoma who were treated with transcatheter arterial embolization (TAE) or
      lipiodolized transcatheter arterial infusion (L-TAI). We investigated the
      incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI
      was performed. All patients who experienced nausea and vomiting received OND
      administered prophylactically at the time of the next TAE or L-TAI to evaluate
      the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during
      the week following arterial chemo-embolization were 44.8% and 27.6%,
      respectively. There was a tendency for the incidence to be higher in patients
      treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those
      treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the
      patients stated that they ate "half or more than half" of the food provided on
      the day of arterial chemo-embolization. The rate improved as time went on. In 5
      patients who experienced nausea and vomiting at the time of arterial chemo
      embolization, nausea and vomiting were inhibited satisfactorily by OND. When
      arterial chemo-embolization was performed, antiemetic treatment for approximately
      3 days was necessary to improve patients' quality of life (QOL) to an acceptable
      level, and OND was found to be effective for the purpose in our 5 patients who
      had experienced nausea and/or vomiting at the previous treatment.

PMID- 10089089
TI  - Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as
      empiric therapy for fever in severely neutropenic patients.
AB  - The objective of this trial was to evaluate the potential advantages of the
      combination of piperacillin and tazobactam in the control of fever in neutropenic
      patients. In this single-center study, patients who experienced a total of 247
      febrile episodes were prospectively randomized to receive either our standard
      regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5
      mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g
      t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added
      in all cases of persistent fever in the ceftazidime arm, but only when there was
      microbiologically documented resistance in the piperacillin/tazobactam arm. All
      247 episodes were evaluable by "intent-to-treat" analysis. The two populations
      were well matched in terms of age, gender, underlying disease, chemotherapy
      received, oral decontamination, clinical and bacterial documentation, and
      severity and duration of neutropenia. Initial antibacterial therapy was
      successful (apyrexia at 72 h, without antibiotic change) more frequently (P =
      0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the
      one including ceftazidime (37.6%). Fewer (P = 0.02) major infectious events
      (infectious death or delay in treatment of underlying disease due to infection)
      were observed during piperacillin/ tazobactam treatment (2.6%) than with the
      ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition
      when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules
      adopted. This trial confirmed the efficacy of the piperacillin/tazobactam
      combination for empirical treatment of febrile neutropenic patients. This
      antibiotic combination permitted a dramatic decrease in empiric glycopeptide
      antibiotic administration in such patients.

PMID- 10089090
TI  - Mechanical ventilation in critically ill cancer patients: outcome and utilisation
      of resources.
AB  - Intensive care is increasingly being used in the management of cancer patients.
      It is important that a disproportionate share of special care resources is not
      expended on futile care of terminally ill patients. A requirement for mechanical
      ventilation has been stated to affect survival in cancer patients. The objectives
      of this study were to determine our hospital utilisation of ICU facilities and
      the prospects of a successful outcome in cancer patients with a need for
      ventilatory support. The Norwegian Radium Hospital is a 400-bed cancer hospital
      with a 12-bed combined postoperative and intensive care unit (PO/ICU). For each
      patient admitted to the PO/ICU, patient data including diagnosis, therapeutic
      interventions, use of resources and outcome are entered in a computerised
      database. We reviewed all 10,051 patients admitted during a 5-year period,
      focusing on the patients receiving ventilatory support. There were 347 patients
      who were treated with mechanical ventilation, 228 patients only for a short
      period postoperatively after extensive surgery. A further 119 patients (mean age
      68 years, mean SAPS 33.5) were treated with mechanical ventilation for more than
      24 h or died during treatment in the ICU; 65 patients (55%) were admitted after
      elective surgery, 24 (20%) after surgical emergencies and 30 (25%) after medical
      emergencies. Metastatic disease was present in 59% of them. These 119 patients
      comprised 1.18% of all patients admitted to the PO/ICU, but utilised 28% of all
      resources. They included 34 patients (29%) who died during the ICU stay, while 69
      patients (58%) were still alive after 6 months. The ICU mortality in different
      groups was: surgical patients 24%, gynaecological patients 9%, oncological
      patients 63%. The mortality in the age group >70 years was 15%. The role of ICU
      facilities, including mechanical ventilation, is important for optimal supportive
      care in cancer patients. Our results indicate that this treatment modality should
      not generally be restricted in critically ill cancer patients. The quality of
      life of the patients who survived should be of interest to those involved in
      further medical and ethical decisions concerning the level of care in the ICU.

PMID- 10089091
TI  - Microbiological safety of essential oils used in complementary therapies and the
      activity of these compounds against bacterial and fungal pathogens.
AB  - To determine the safety of plant essential oils we determined the sterility of
      eight of these products obtained from retail outlets. In addition, the ability of
      oils to support the growth of fungal and bacterial pathogens was examined. The
      antimicrobial activity of these products against seven bacterial species and
      Candida albicans was also investigated. All oils and their respective carriers
      were sterile. Methicillin-resistant Staphylococcus aureus and Pseudomonas
      aeruginosa were unable to survive in oils for longer than 6 h, whereas C.
      albicans was able to survive, but not multiply, in ylang ylang oil for at least
      48 h.

PMID- 10089092
TI  - Taguchi optimisation of ELISA procedures.
AB  - We propose a new method in the field of ELISA optimization using an experimental
      design called the Taguchi method. This can be used to compare the net effects of
      different conditions which can be both qualitative and quantitative in nature.
      The method reduces the effects of the interactions of the optimized variables
      making it possible to access the optimum conditions even in cases where there are
      large interactions between the variables of the assay. Furthermore, the proposed
      special assignment of factors makes it possible to calculate the biochemical
      parameters of the ELISA procedure carried out under optimum conditions. Thus, the
      calibration curve, the sensitivity of the optimum assay, the intra-assay and
      inter-assay variability can be estimated. The method is fast, accessing the
      results in one step, compared to the traditional, time-consuming 'one-step-at-a
      time' method. We exemplify the procedure with a method to optimize the detection
      of ScFv (single chain fragment of variable) phages by ELISA. All the necessary
      calculations can be carried out by a spreadsheet program without any special
      statistical knowledge.

PMID- 10089093
TI  - Immunoenzymatic detection of the new proliferation associated protein p100 by
      means of a cellular ELISA: specific detection of cells in cell cycle phases S, G2
      and M.
AB  - In vitro proliferation assays are widely used in biomedical research. We describe
      the immunoenzymatic (ELISA) detection of a recently described proliferation
      associated protein (p100) by means of a new monoclonal mouse IgG1 antibody (Ki
      S2). P100 is a 100 kDa nuclear protein that is specifically detected during the
      cell cycle phases S, G2 and M. Comparative studies on lectin-stimulated
      leukocytes using 3H-thymidine labelling and Ki-67 antibodies revealed a
      statistically significant positive correlation. Since p100 is absent in GO and G1
      cells, its detection permits the precise and specific measurement of actual cell
      cycle events under culture conditions.

PMID- 10089094
TI  - Production and characterization of polyclonal antibodies against cholecalciferol
      (vitamin D3).
AB  - Vitamin D is one of the essential vitamins in the human diet for normal growth
      and function. In Canada and the USA, fortified milk and milk products are the
      essential source of vitamin D. The adult recommended nutrient intake of vitamin D
      is 200 to 400 I.U. (corresponding to 5 to 10 microg) per day. Additional amounts
      of vitamin D do not confer benefits and may even be toxic. However, a deficiency
      of this vitamin leads to inadequate absorption of calcium and phosphorus and
      faulty mineralization of bones and teeth. Actual methods for measuring vitamin D
      in milk are limited in terms of sensitivity, rapidity and simplicity. The
      objective of this manuscript was to develop a new molecular strategy for the
      production, purification and characterization of polyclonal antibodies to vitamin
      D. Specific antibodies were raised in rabbits against vitamin D using cationized
      bovine serum albumin (cBSA) as a carrier protein. Anti-vitamin D antibodies were
      recovered from rabbit sera by sequential affinity chromatographies through
      Protein A/G Agarose, cBSA Sepharose and cOVA-vitamin D Sepharose columns.
      Although the yields of anti-vitamin D were relatively low, recovered antibodies
      showed high specificity and affinity to vitamin D. The purified antibody was used
      to develop a solid-phase enzyme immunoassay in order to determine the exact
      concentration of vitamin D in phosphate buffer. Using this immunoassay,
      approximately 35 ng of vitamin D can be detected within 3 h. The signal obtained
      was proportional to the amount of vitamin D in the sample analyzed. The strategy
      developed in this paper appears to be very promising in terms of sensitivity,
      rapidity and simplicity. It offers a great potential for automation and use on a
      routine basis for the quantification of vitamin D in fortified milk and other
      milk products.

PMID- 10089095
TI  - Continuous antibody production by phytohemagglutinin-L-aggregated hybridoma
      cells.
AB  - Phytohemagglutinin-L (PHA-L) induced aggregation of SP2 myeloma and antibody
      producing hybridoma cells. The aggregates were of diverse shapes, and major-axis
      length of the hybridoma aggregates was mostly 50-80 microm at 1 microg/ml PHA-L
      and 100-150 microm at 5 microg/ml. PHA-L did not suppress growth rate at these
      concentrations. The aggregated cells had almost the same antibody productivity as
      that of non-aggregated cells in a static culture. Essentially, identical results
      were obtained with soybean agglutinin (SBA). On the other hand, pokeweed mitogen
      (PWM) did not induce apparent aggregation at a concentration of 10 microg/ml.
      These results suggest that lectin binding to particular carbohydrate moiety on
      the cell surface is necessary for cell agglutination. Using PHA-L, a 200-ml
      suspension culture of aggregated hybridoma cells was successfully performed in a
      spinner flask over 10 days. The aggregates were mainly globular with a diameter
      of 50-100 microm at 1-2 microg/ml PHA-L. The aggregation greatly enhanced
      settlement of hybridoma cells by gravity, and medium exchanges were thereby
      easily performed in a short period. During a course of the semi-continuous
      culture, antibody concentrations of culture medium were maintained at
      approximately 10 microg/ml which was comparable to that of static culture of the
      aggregated hybridoma cells. Thus, the lectin aggregation is applicable to the
      separation of culture medium from anchorage-independent cells like hybridomas,
      and can be employed in a large-scale commercial production of biologically active
      proteins.

PMID- 10089096
TI  - Immunoadhesins of interleukin-6 and the IL-6/soluble IL-6R fusion protein hyper
      IL-6.
AB  - Signal transduction in response to interleukin-6 (IL-6) results from
      homodimerization of gp130. This dimerization occurs after binding of IL-6 to its
      surface receptor (IL-6R) and can also be triggered by the complex of soluble IL
      6R and IL-6. We fused IL-6 to the constant region of a human IgG1 heavy chain
      (Fc). IL-6Fc was expressed in COS-7 cells and purified via Protein A Sepharose.
      Using three different assays we found that the biological activity of this
      dimeric IL-6 protein is comparable with monomeric IL-6. Recently, we described
      the designer cytokine Hyper-IL-6 (H-IL-6) in which soluble IL-6R and IL-6 are
      connected via a flexible peptide linker. This molecule turned out to be 100-1000
      times more effective than unlinked IL-6 and soluble IL-6R. Hyper-IL-6 acts on
      cells only expressing gp130 and is a potent stimulator of in vitro expansion of
      early hematopoietic precursors. Here we show that a Fc fusion protein of H-IL-6
      (H-IL-6Fc) has the same biological activity on BAF/gp130 cells as H-IL-6.
      Furthermore, both H-IL-6 forms have a similar ability to induce the synthesis of
      acute phase proteins in human hepatoma cells HepG2 and in mice in vivo. The
      introduction of a thrombin cleavage site between H-IL-6 and the Fc portion of H
      IL-6Fc made it possible to specifically recover biologically active monomeric H
      IL-6 by limited proteolysis of the fusion protein. A more general use of
      cleavable immunoadhesins expressed in mammalian cells is discussed.

PMID- 10089097
TI  - Suitability of cell metabolic colorimetric assays for assessment of CD4+ T cell
      proliferation: comparison to 5-bromo-2-deoxyuridine (BrdU) ELISA.
AB  - The conventional tritiated thymidine (3H-TdR) incorporation assay is considered
      as the 'gold standard' for the assessment of cell growth. However, the 3H-TdR
      incorporation assay has several disadvantages which have prompted the development
      of nonradiolabelling proliferation assays such as 5-bromo-2-deoxyuridine (BrdU)
      ELISA, tetrazolium microplate assay and acid phosphatase assay. In studies, these
      three proliferation assays have shown equivalent sensitivity and reproducibility
      to the 3H-TdR incorporation assay. However the results may be affected by the
      cell type studied. In the present study, we have used these three proliferation
      assays for the assessment of rat lymph node CD4 + T lymphocyte growth in response
      to polyclonal antigen stimulation. The proliferation assays were compared on the
      basis of four criteria: sensitivity, reproducibility, stimulation index and
      insensitivity of the assay to the cell number. Our results indicated that the
      BrdU ELISA demonstrated the highest sensitivity, reproducibility and stimulation
      index but had a limited linear range for cellular growth. The tetrazolium
      microplate assay also had a relatively good sensitivity, reproducibility,
      stimulation index and a wider linear response range for cell growth in comparison
      to the BrdU ELISA. The acid phosphatase assay showed the lowest reproducibility
      and stimulation index. Because BrdU incorporation in DNA of proliferating cells
      has been reported to block cell division, we have investigated this possibility
      in sequential assays. Our results indicated that in our experimental conditions
      no evidence of an anti-mitogenic action of BrdU was observed. We also compared
      the performance of the MTS assay and BrdU ELISA in measuring substance P-induced
      CD4 + T cell proliferation. The results indicated that the MTS assay may reflect
      change in cell activation leading to an overestimate of cell growth. In
      conclusion, our results indicate that the BrdU ELISA is the most sensitive of the
      three proliferation assays used for the assessment of CD4 + T lymphocyte growth
      and is the preferred assay when small changes in cell growth are expected.

PMID- 10089098
TI  - A novel method of cell separation based on dual parameter immunomagnetic cell
      selection.
AB  - We describe a novel method of cell purification involving two stage
      immunomagnetic selection which permits isolation of cells based on a second cell
      surface marker without the need for removal of beads used in the first selection
      step. This approach takes advantage of the size differences between commercially
      available immunomagnetic beads and/or particles and their differing properties in
      terms of attraction to magnetic fields of various strengths. The first stage of
      separation involves positive selection of cells using the Miltenyi MiniMacs
      system, utilising 50 nm MicroBeads and a MiniMacs magnet. Cells obtained from
      this procedure--still rosetted with 50 nm MicroBeads--can then be subjected to
      further positive or negative selection using either streptavidin M280 or anti-rat
      M450 Dynabeads, without the need for prior bead removal, since the strength of
      the magnetic field of the Dynal separator is sufficient to attract the larger
      Dynabeads but not the MicroBeads. Here, we show that this system can be used to
      isolate a number of cell types including very rare target cell populations such
      as haemopoietic stem cells, using two different surface markers without
      perturbing subsequent functional capacity.

PMID- 10089099
TI  - Molecular analysis of the complementarity determining region 3 of the human T
      cell receptor beta chain. Establishment of a reference panel of CDR3 lengths from
      phytohaemagglutinin activated lymphocytes.
AB  - The T cell receptor (TCR) repertoire of a lymphocyte population may be
      characterized by the distribution of lengths of the hypervariable fragment known
      as the complementarity determining region 3 (CDR3). Immunological activity
      leading to clonal predominance will result in an over-representation of given
      CDR3 lengths and a distortion of the CDR3 length distribution. CDR3 length
      distribution may be studied by the in vitro amplification of TCRB cDNA followed
      by gel electrophoresis of the resulting product. We have established a simple,
      robust method for the evaluation of CDR3 length distribution in human lymphocyte
      samples. The CDR3 length distribution in phytohaemagglutinin (PHA) activated
      lymphocytes from a large number of healthy donors was established as a reference
      panel for each of 22 human TCR beta variable (BV) families. We propose that an
      abnormal CDR3 length distribution be defined as one in which one or more CDR3
      lengths exceed the upper confidence limit (5% significance, one-sided test) given
      by this PHA reference population. Using this criterion in titration experiments,
      we were able to identify a clone when it constituted 2% of the cells analyzed.
      Over-dilution of cellular material or cDNA may produce falsely abnormal CDR3
      length distributions. A nested technique using two separate amplification steps
      was found to yield results comparable in quality to the single amplification
      technique. When few cells are available, the nested method gives more material
      for CDR3 length analyses. However, it does not reduce the likelihood of a falsely
      abnormal distribution being recorded when the cellular material is too scarce.

PMID- 10089100
TI  - Influence of antibody valency in a displacement immunoassay for the quantitation
      of 2,4-dichlorophenoxyacetic acid.
AB  - The influence of antibody valency in a displacement immunoassay was investigated
      by comparing the whole antibody molecule with the corresponding Fab-fragment. The
      displacement immunoassay for the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)
      takes advantage of the cross-reactivity of monoclonal anti-2,4-D antibodies and
      the Fab-fragments toward immobilized 2-methyl-4-chlorophenoxyacetic acid (MCPA).
      Due to the low affinity of the antibodies toward MCPA (cross-reactivity of
      approximately 30%), the addition of 2,4-D resulted in a displacement of the
      antibodies or the fragments. The detection limits obtained with whole anti-2,4-D
      antibodies and Fab-fragments were 0.1 microg/l and 0.01 microg/l 2,4-D,
      respectively. The whole antibodies and the Fab-fragments show similarities, such
      as the cross-reactivity toward MCPA (26% and 33%), and some characteristics of
      the calibration curve, for example the large detection range and the sensitivity.
      In contrast to the bivalent antibodies, however, increasing the hapten/protein
      ratios of the immobilized MCPA-BSA conjugates did not affect the detection limit
      when using the Fab-fragments. Moreover, kinetic experiments reveal a faster
      displacement reaction with the Fab-fragments. A disadvantage of using the Fab
      fragments is the generation of lower absorbance values in the ELISA.

PMID- 10089101
TI  - A novel assay for detecting antibodies to cytochrome P4502D6, the molecular
      target of liver kidney microsomal antibody type 1.
AB  - Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of
      autoimmune hepatitis type 2, is also found in a proportion of patients with
      hepatitis C virus infection (HCV). It is detected conventionally by the
      subjective immunofluorescence technique. Our aim was to establish a simple and
      objective enzyme-linked immunosorbent assay (ELISA) that measures antibodies to
      cytochrome P4502D6 (CYP2D6), the target of LKM1. An indirect ELISA using
      eukaryotically expressed CYP2D6 was designed. Absorbance values obtained against
      a reference microsomal preparation were subtracted from those obtained against a
      microsomal preparation over-expressing CYP2D6, thus removing the non-CYP2D6
      specific reaction. Sera from 51 LKM1 positive patients (21 autoimmune hepatitis
      and 30 with HCV infection), 111 LKM1 negative patients with chronic liver disease
      (including 20 with HCV infection) and 43 healthy controls were tested. Of 51
      patients positive by immunofluorescence, 48 were also positive by ELISA while all
      the 154 LKM1 negative subjects were also negative by ELISA. There was a high
      degree of association between IFL and ELISA as demonstrated by a kappa
      reliability value of 0.96. The absorbance values by ELISA correlated with
      immunofluorescence LKM1 titres both in autoimmune hepatitis (r = 0.74, p < 0.001)
      and HCV infection (r = 0.67, p < 0.001). The simple, objective ELISA described
      has the potential to replace the standard immunofluorescence technique.

PMID- 10089102
TI  - An assay for the quantitative measurement of in vitro phagocytosis of early
      apoptotic thymocytes by murine resident peritoneal macrophages.
AB  - Research into the mechanisms by which apoptotic cells are phagocytosed has grown
      considerably over recent years, together with a growing appreciation of the
      importance of clearance of redundant cells for tissue homeostasis. However,
      studies addressing the efficacy of phagocytosis have been rare. The few studies
      reported to date were either attempts to determine apoptotic cell clearance from
      the circulation or were focused on clearance in inflammation. We now describe an
      in vitro assay which permits the quantitative measurement of phagocytosis of
      apoptotic cells by murine resident peritoneal macrophages. The apoptotic cells
      used in the assay were murine thymocytes incubated with dexamethasone for only 3
      h. Most apoptotic thymocytes were annexin V positive and propidium iodide
      negative and therefore still in the earlier stages of apoptosis. The assay was
      completed 7 h after the isolation of both macrophages and thymocytes, while
      macrophage culture time was only 4 h. Because of this short-term culture it is
      likely that the resident peritoneal macrophages largely maintained their in vivo
      phenotype. Using BALB/c macrophages and thymocytes, the maximal in vitro
      phagocytosis exceeded five thymocytes per macrophage in 1 h and two of these
      thymocytes were taken up within 10 min. Therefore, in vitro phagocytosis by
      resident peritoneal macrophages was rapid and of high capacity, as it is
      postulated to be in vivo. Under selected conditions, the mean uptake was 4.45+/
      0.70 (mean +/- SD, n = 31) thymocytes per macrophage in 1 h. The inter-assay
      coefficient of variation, also representing the biological variability, was found
      to be 15.7%. The average intra-assay coefficient of variation was 13.6%. This
      assay permits comparisons of phagocytic efficacy between different strains of
      mice in vitro. In addition, a method of preparation is described which allows
      long-term storage of experimental results. Finally, our data suggests that
      internalization, but not binding of apoptotic cells to short-term cultured
      resident peritoneal macrophages, is critically dependent on the presence of
      serum. This allows separate analysis of binding and internalization of apoptotic
      cells with the assay, without the necessity to use agents blocking
      internalization.

PMID- 10089103
TI  - Heat inactivation of fetal calf serum is not required for in vitro measurement of
      lymphocyte functions.
AB  - This study was undertaken to test whether fetal calf serum (FCS) must be heat
      inactivated before use in tissue culture. We tested various immune functions of
      lymphocytes growing in medium containing non-treated and heat-inactivated FCS.
      The data clearly show that heat inactivation of the serum is not mandatory. In
      some cases, the addition of untreated FCS resulted in elevated response levels,
      while maintaining immune function specificity.

PMID- 10089104
TI  - Efficient generation of transgenic BALB/c mice using BALB/c embryonic stem cells.
AB  - BALB/c is one of the most widely used and best characterized mouse strains in
      immunology. For various applications, it is necessary to generate BALB/c
      transgenic mice. However, using the conventional microinjection technique it is
      extremely inefficient to produce transgenic BALB/c mice since the one-cell stage
      BALB/c embryos are highly vulnerable to pronuclear DNA microinjection. To
      overcome this problem, we have investigated the generation of Egr-1 (early growth
      response gene) transgenic mice via the transfection of BALB/c embryonic stem
      cells. Transfectants carrying Egr-1 constructs comprising either the
      immunoglobulin heavy chain or the MHC class II promoter/enhancer system were
      injected into C57BL/6 host blastocysts resulting in chimeric mice. For both type
      of expression vectors, transgenic offspring of the germline chimeras expressed
      recombinant Egr-1 in lymphoid tissues containing B cells. This demonstrates the
      successful generation of Egr-1 transgenic BALB/c mice using transfected ES cell.

PMID- 10089105
TI  - Nomenclature of immunoglobulin A and other proteins of the mucosal immune system.
      IUIS/WHO subcommittee on IgA nomenclature.
AB  - The predominant immunoglobulin found in exocrine secretions of humans and most
      other mammals is secretory IgA, a polymeric form of IgA containing an additional
      glycoprotein chain designated "secretory component". In this article recommended
      abbreviations are proposed for the following forms of human IgA and other
      proteins of related interest: secretory IgA, secretory IgM, secretory component,
      polymeric immunoglobulin receptor, polymeric IgA, monomeric IgA, IgA subclass 1,
      IgA subclass 2, A2 allotype marker 1, and A2 allotype marker 2.

PMID- 10089106
TI  - Natural history of colorectal cancer.
AB  - Colorectal cancer arises from a precursor lesion, the adenomatous polyp, which
      forms in a field of epithelial cell hyperproliferation and crypt dysplasia.
      Progression from this precursor lesion to colorectal cancer is a multistep
      process, accompanied by alterations in several suppressor genes that result in
      abnormalities of cell regulation, and has a natural history of 10-15 years.
      Environmental factors and inherited susceptibility play major roles in this
      sequence of events. As a result of familial and genetic studies, we now have a
      better understanding of various high-risk groups and the application of screening
      methods to these individuals and to people at average risk. In the future,
      further identification of genetically predisposed individuals and colonoscopic
      screening of the general population may provide new opportunities for control of
      colorectal cancer through secondary prevention, and a better understanding of
      lifestyle factors and their modification will lead to improved strategies for
      primary prevention.

PMID- 10089107
TI  - Screening guidelines for colorectal cancer.
AB  - Evidence-based guidelines recommend that all asymptomatic, average-risk U.S.
      citizens >50 years of age be encouraged to undergo screening for colorectal
      cancer. Those at higher risk should be offered more intensive screening and
      follow-up surveillance. It is estimated that widespread adoption of these
      recommendations could reduce mortality from colorectal cancer by >50%. The only
      screening methods that have been evaluated directly are the fecal occult blood
      test and flexible sigmoidoscopy. Current guidelines now recommend annual
      screening for fecal occult blood plus flexible sigmoidoscopy every 5 years for
      asymptomatic, average-risk men and women >50 years of age. Indirect evidence
      supports the options of colonoscopy or barium enema x-ray screening for highly
      motivated individuals, but these methods have not yet been tested in prospective
      trials. In the future, gene-based screening tests may be developed, and computed
      tomography of the colon ("virtual colonoscopy") may prove effective and feasible.

PMID- 10089108
TI  - Diet and lifestyle in the prevention of colorectal cancer: an overview.
AB  - Numerous lifestyle factors have been implicated in colorectal carcinogenesis.
      These include diet, inadequate physical activity, obesity, alcohol consumption,
      and smoking. Epidemiologic studies, animal experiments, and randomized clinical
      trials have shown that dietary factors can influence all stages of colorectal
      carcinogenesis, from cell proliferation to transformation to cancer. Defining the
      precise role of diet and other lifestyle factors in colorectal carcinogenesis may
      require the elucidation of genetic susceptibility and genetic-environmental
      interactions. Despite the preoccupation with nutrition by the public and the
      media in the United States, trends in food consumption have not been favorable.
      The average U.S. diet is still too high in calories and fat and too low in fiber,
      cereals, fruits, and vegetables. Dietary modifications along with secondary
      prevention measures may have a major impact on reducing the mortality from
      colorectal cancer.

PMID- 10089109
TI  - Role of dietary fiber in colon cancer: an overview.
AB  - Studies have demonstrated a reduced risk of colon cancer when populations with
      diets high in total fat switched to a diet high in total fiber and certain whole
      grain foods. Case-control studies have shown convincingly the relationship
      between dietary fiber and colon cancer. Studies in animal models have
      demonstrated that the inhibitory effects of dietary fiber on the development of
      colonic neoplasms depend on the nature and source of the fiber; that wheat bran
      appears to inhibit colon tumor development more consistently than do other
      dietary sources of fiber, such as oat and corn bran; and that dietary
      administration of phytic acid, high levels of which are present in wheat bran,
      inhibits colon carcinogenesis. Human dietary intervention studies have also
      indicated that the modifying effect of dietary fiber on bacterial enzymes
      involved in the production of putative colon tumor promoters depends on the type
      of fiber consumed. Dietary wheat bran, but not oat or corn bran, significantly
      decreased the levels of several tumor promoters in the colon, independent of
      stool bulk.

PMID- 10089110
TI  - Nutritional regulation of gene expression.
AB  - Genes are regulated by complex arrays of response elements that influence the
      rate of transcription. Nutrients and hormones either act directly to influence
      these rates or act indirectly through specialized signaling pathways. Metabolites
      of vitamins A and D, fatty acids, some sterols, and zinc are among the nutrients
      that influence transcription directly. Components of dietary fiber may influence
      gene expression indirectly through changes in hormonal signaling, mechanical
      stimuli, and metabolites produced by the intestinal microflora. In addition,
      consumption of water-soluble fibers may lead to changes in gene expression
      mediated through indirect mechanisms that influence transcription rates. In the
      large intestine, short-chain fatty acids, including butyric acid, are produced by
      microflora. Butyric acid can indirectly influence gene expression. Some sources
      of fiber limit nutrient absorption, particularly of trace elements. This could
      have direct or indirect effects on gene expression. Identification of genes in
      colonic epithelial cells that are differentially regulated by dietary fiber will
      be an important step toward understanding the role of dietary factors in
      colorectal cancer progression.

PMID- 10089111
TI  - Potential protective mechanisms of wheat bran fiber.
AB  - Experimental studies using high-fiber supplements show that of all the fibers
      tested, wheat bran is the most effective in protecting against colon tumor
      development. The mechanisms behind this protective effect have not been
      elucidated completely, and the effect is most likely multifactorial. Some
      mechanisms, such as luminal dilution of potential carcinogens and accelerated
      transit through the colon, are well established. The fermentation of wheat fiber
      to short-chain fatty acids--especially butyric, which has been shown to inhibit
      tumor growth in vitro--is documented, but interpretation of the data from animal
      studies and clinical trials is subject to debate. Several potential mechanisms,
      such as effects of phytochemicals and phytates contained in wheat bran, have not
      yet been explored.

PMID- 10089112
TI  - Protective role of wheat bran fiber: preclinical data.
AB  - Although animal data relating to the effects of dietary fiber on experimentally
      induced colon tumors are not easily summarized, it appears that wheat bran fiber
      protects against colon cancer. In a recent direct comparison, an ad libitum diet
      containing wheat bran fiber led to a 40% lower incidence of colon tumors,
      compared with a cellulose-containing diet. In addition, the greater protective
      effect of wheat bran fiber as compared with the cellulose was shown in rats fed
      10% or 20% energy-restricted diets containing wheat bran or cellulose.

PMID- 10089113
TI  - Protective role of wheat bran fiber: data from marker trials.
AB  - The effects of wheat bran fiber on surrogate endpoint biomarkers for colon cancer
      risk have been studied in rats and humans. In both species, there is little
      evidence that wheat bran fiber significantly modifies epithelial cell
      proliferation. In rat studies, however, dietary supplementation with wheat bran
      fiber has decreased mucosal formation of aberrant crypt foci, an important marker
      currently used to estimate the efficacy of colon cancer chemoprevention agents.
      In humans, wheat bran fiber has been shown to consistently decrease fecal bile
      acid concentrations, mainly by reducing toxic secondary bile acids.

PMID- 10089114
TI  - Wheat bran fiber and development of adenomatous polyps: evidence from randomized,
      controlled clinical trials.
AB  - Mutations in oncogenes and tumor suppressor genes are thought to initiate and
      promote the pathway to colorectal cancer, leading to hyperproliferation, the
      development of adenomas, and progression to gross malignancy. Intervention at any
      of these steps can potentially prevent the development of cancer. Several
      randomized, controlled trials have investigated the effect of dietary
      interventions, including the addition of wheat bran fiber, on the development of
      adenomatous polyps. In a familial adenomatous polyposis trial, patients were
      treated with 4 g of ascorbic acid plus 400 mg of alpha-tocopherol per day alone
      or with a grain fiber supplement (22.5 g/day) over a 4-year period. On an actual
      intake basis, the combined intervention inhibited the development of rectal
      polyps. However, the Toronto Polyp Prevention Trial found no significant
      differences in polyp recurrence rates between patients who were counseled to
      follow a low-fat, high-fiber diet and patients consuming a typical Western diet
      with placebo fiber. A 9-month study of patients with resected colon adenomas
      found that dietary wheat bran fiber significantly reduced total, primary, and
      secondary fecal bile acid concentrations and excretion rates. Such bile acid
      levels are thought to be related to the risk of developing cancer. The Australian
      Polyp Prevention Project reported that the combination of fat reduction and a
      supplement of wheat bran reduced the incidence of large colorectal adenomas.
      These latter results suggest that intervention with a low-fat wheat bran
      supplemented diet inhibits the transition from smaller to larger adenomas, which
      may be a critical step in determining which adenomas progress to malignancy.

PMID- 10089115
TI  - Progress report: the Arizona phase III study of the effect of wheat bran fiber on
      recurrence of adenomatous colon polyps.
AB  - A double-blind, placebo-controlled Phase III cancer prevention trial in subjects
      with previous resection of adenomatous colon polyps is nearing completion. The
      study's primary objective is to evaluate the effects of daily dietary
      supplementation with large (13.5 g/day) versus small (2.0 g/day) doses of wheat
      bran fiber for 3 years. A summary of the study design and a progress report are
      presented.

PMID- 10089117
TI  - Foreword 

PMID- 10089116
TI  - Implementation of dietary modifications.
AB  - Recommendations for dietary fiber intake for adults fall within the range of 20
      35 g/day, or 10-13 g/1,000 kcal. However, popular U.S. foods are not high in
      dietary fiber, and common serving sizes of grains, fruits, and vegetables contain
      only 1-3 g of dietary fiber. In spite of the widespread dissemination of the
      recommendations for fiber consumption, however, the usual intake of dietary fiber
      in the United States remains lower than these recommended levels, averaging only
      14-15 g/day. It is generally recommended that constipation be treated with a
      concentrated source of insoluble fiber, and cholesterol can be lowered with
      soluble fiber, as suggested by claims made for oat bran and psyllium. Scientific
      evidence supports the role of wheat bran fiber in reducing the risk of colorectal
      cancer, yet this message needs to be delivered to the average consumer. Most
      surveys suggest that coarse, brown fiber is not well accepted, as consumers say
      such foods "taste bad." Implementation of guidelines for increased intake of
      wheat bran fiber will require public education on the importance of this
      recommendation. Further, consumers need to be convinced that wheat bran fiber can
      taste good by the development of a wide range of products high in wheat bran
      fiber that can be consumed throughout the day.

PMID- 10089118
TI  - Editor's preface: adolescents and religion: a view from the millenium 

PMID- 10089119
TI  - Psychology of religion and adolescents in the United States: past to present.
AB  - Many of the early founders of America were concerned with religious issues, and
      some of their concerns continue in contemporary science. Psychology of religion
      has a long history in American psychology, but one marred by neglect and
      misguided claims about the nature of science. Psychology of religion offers a
      chance for an expansion of behavioral science into realms of importance to many
      people. For example, both development during adolescence and the implications of
      gender differences may be illuminated by a consideration of the role of religion
      in human life. Particular topics discussed include conversion and religious
      mobility, religious experience, images of God, identity, and mental health and
      coping.

PMID- 10089120
TI  - Religious involvement and adolescent psychosocial development.
AB  - The purpose of this study was to determine if religious involvement was
      associated with psychosocial maturity of adolescents as understood in Erikson's
      psychosocial theory. Three forms of religious involvement (attendance at
      religious services, participation in a Bible study group, and youth group
      involvement) were examined in relation to ego strengths, ideological and ethnic
      forms of identity, general self-esteem, and school self-esteem. Questionnaires
      were completed by 62 African-American and 63 European-American students in the
      11th grade. All participants were from rural areas in West Virginia and of lower
      income status. Ego strengths of hope, will, purpose, fidelity, love, and care
      were associated with various forms of religious involvement. These associations
      were most apparent for European-Americans. Although ideological identity was not
      related to religious involvement, higher ethnic identity was associated with
      being African-American, especially for those more religiously involved. General
      self-esteem was not significant in the analyses, but school self-esteem was
      higher for each form of religious involvement.

PMID- 10089121
TI  - Effects of religiosity and racial socialization on subjective stigmatization in
      African-American adolescents.
AB  - The direct effects of religiosity and racial socialization on subjective
      stigmatization among 50 African-American adolescents were investigated. A stigma
      is a characteristic about which others hold negative attitudes and stereotypes.
      Subjective stigmatization measures the degree to which an individual internalizes
      such negative attitudes and stereotypes toward a social group of which he or she
      is a member. Participants who showed strong commitment to the church were more
      destigmatized than were participants who did not. Further, participants who
      received racial socialization messages stemming from a single "primary" category
      were more destigmatized than those who did not. Unexpectedly, the more racial
      socialization messages participants received, the more self-stigmatized they
      were. The importance of religiosity and racial socialization in the lives of
      African-American adolescents are discussed.

PMID- 10089122
TI  - Religion, community service, and identity in American youth.
AB  - The role of religion in identity development has, for many years, been a
      relatively neglected topic in psychology. To demonstrate the importance of
      religion to the formation of identity, this paper presents evidence connecting
      community service and religiousness in American youth. Data are reviewed that
      show (1) youth are heavily involved in volunteer service; (2) many youth view
      religion as important and those who do so are more likely to do service than
      youth who do not believe that religion is important in their lives; (3)
      involvement in church-sponsored service makes it more likely that youth will
      adopt the religious rationale in which service is couched; and (4) youth who do
      church-sponsored service are neither service "nerds" nor single-issue tunnel
      visioned adolescents. These data from nationally representative samples
      strengthen the case that the many contemporary youth who take religion seriously
      are vibrantly engaged in their schooling, in the betterment of communities, and
      the development of identities which presage healthy lives.

PMID- 10089123
TI  - Off-road religion? A narrative approach to fundamentalist and occult orientations
      of adolescents.
AB  - Results of qualitative biographical research on Christian fundamentalist converts
      and de-converts, and on occultist adolescents are presented and documented using
      case studies. Research focused on life themes and on biographical processes and
      transformations. Contrastive comparison of the cases resulted in typologies of
      Christian fundamentalist biographies and of "ways of dis-enchantment". These
      indicate that obligation to a tradition is no longer the model for religious
      socialization. Its competitors are biographical trajectories which can have the
      following characteristics: heresy is taken for granted, religious search is like
      an open life-style preference (accumulative heretic); ritual coping with life
      themes is predominant; and religious search follows the motive of sensation
      seeking. A typology of religious styles is applied as an interpretive framework
      for (a) explaining the formation of fundamentalist orientations and (b)
      understanding development and transformation in religious biographies.

PMID- 10089124
TI  - Some clinical applications of religious development in adolescence.
AB  - The use of religion in the lives of adolescents to repair problematic or
      disrupted attachments is discussed in the context of attachment theory and
      Kohut's self-psychology theory, with particular reference to the self-object. It
      is proposed that adolescents do not seek to break ties with parents or adults so
      much as to revise their relationships in a more adult direction. Two adolescent
      cases, one beginning treatment in childhood and the other in early adolescence,
      are presented and discussed in the context of attachment theory and self
      psychology.

PMID- 10089125
TI  - Prayer in the lives of late adolescents.
AB  - Prayer is a behavior that is performed by most people at least at some time, and
      yet social scientists appear to have neglected this topic. College students were
      interviewed, given the Objective Measure of Ego Identity Status, and asked to
      keep 7-day diaries about their prayer activities, whether spontaneous or formal.
      Correlational analyses revealed a relationship between identity status and
      frequency of praying, as well as between identity status and commitment to
      religion. A qualitative analysis of the diary data suggested that prayer may be a
      revealing approach to the psychosocial lives of late adolescents, including their
      central concerns, temporal orientation, and the social bounds of their definition
      of self.

PMID- 10089128
TI  - Reviewers 

PMID- 10089126
TI  - Religious development in adolescence 

PMID- 10089129
TI  - Rat interleukin 6: expression in recombinant Escherichia coli, purification and
      development of a novel ELISA.
AB  - Interleukin 6 (IL-6) is a cytokine involved in many aspects of the acute phase
      and immune responses. Cloning of rat IL-6 cDNA into the pET-21d expression
      plasmid under control of a bacteriophage T7 RNA polymerase promoter system
      allowed isopropylthio-galactopyranoside (IPTG)-inducible production of
      recombinant rat IL-6 in Escherichia coli. The cloning, expression and
      purification of rat IL-6 is described. In this expression system, rat IL-6 was
      produced in insoluble inclusion bodies. The protein was solubilized in 6 M
      guanidine hydrochloride and refolded in a glutathione redox system. Refolded rat
      IL-6 was purified to homogeneity using anion-exchange chromatography on SP
      Trisacryl. The purified recombinant rat IL-6 had a molecular mass of 21 756.38+/
      0.25 Da, which is within 0.01% of the predicted value, taking into account
      cleavage of the N-terminal methionine residue and the formation of two disulfide
      bridges. Recombinant rat IL-6 was 2-3-fold more bioactive than the human standard
      preparation in the B9 hybridoma bioassay. Purified rat IL-6 was used to raise
      polyclonal antibodies in sheep and these reagents were used to develop a novel
      rat IL-6 enzyme-linked immunosorbent assay (ELISA). The ELISA is sensitive to 10
      pg/ml and has been shown to detect IL-6 in plasma from rats injected with
      lipopolysaccharide (LPS).

PMID- 10089130
TI  - Phospholipase A2 inhibitors and leukotriene synthesis inhibitors block TNF
      induced NF-kappaB activation.
AB  - Tumour necrosis factor (TNF) is a key regulator of inflammation and immunity. The
      cellular effects exerted by TNF depend, apart from NF-kappaB-directed gene
      transcription, largely on its ability to activate phospholipase A2(PLA2),
      yielding the release of arachidonic acid (AA) and its metabolites. AA
      metabolites, especially the leukotrienes, act as second messengers in TNF
      receptor signalling, as different inhibitors of AA metabolism impair a variety of
      TNF-induced biochemical events. The role, however, of AA and its metabolites in
      TNF-induced NF-kappaB activation is still obscure. Here we report that 4
      bromophenacyl bromide (4-BPB; an inhibitor of PLA2), nordihydroguaretic acid
      (NDGA; a 5-lipoxygenase inhibitor), as well as MK-886 [an inhibitor of 5
      lipoxygenase-activating protein (FLAP)] interfere with TNF-induced NF-kappaB
      mediated transactivation. However, only 4-BPB inhibited the DNA-binding activity
      of NF-kappaB, whereas NDGA and MK-886 did not. Thus, different inhibitors
      interfere at different points in TNF-induced signalling leading to NF-kappaB
      dependent transcription. Artificial induction of AA metabolism induced neither
      DNA-binding activity of NF-kappaB nor NF-kappaB-dependent transactivation. It was
      concluded that although TNF-induced signalling to NF-kappaB-dependent
      transcription is sensitive to inhibitors of AA metabolism at multiple points
      during this signalling, AA release is essential but not sufficient for NF-kappaB
      activation.

PMID- 10089131
TI  - Gene expression during differentiation of human dendritic cells from cord blood
      cd34 stem cells.
AB  - Human cord blood CD34(+)stem cells were allowed to differentiate in the presence
      of cytokines stem cell factor (SCF), granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha) into functional
      CD1a+dendritic cells (DC). A maximum of 1.9 x 10(6) CD1a+ cells were separated
      from the cells generated from 1.2 x 10(6) CD34(+) stem cells from an individual
      donor. The percentage of CD1a+cells separated rose to a maximum of 27% at day 11
      and fell to 8% at 21 days. Reverse transcription-polymerase chain reaction
      analysis showed that interleukin 2 receptor, interleukin 3 receptor, interleukin
      6 receptor, interleukin 12 receptor (IL-12R) and signal transducer and activator
      of transcription (STAT) 3, STAT 4 mRNA was expressed in all CD1a+cell populations
      throughout and appears to be constitutive. Expression of IL-12RmRNA was
      unexpected in CD1a+DC normally considered to be of myeloid lineage. Expression of
      interleukin 12 (IL-12) p40 subunit mRNA was not detected. Intermittent expression
      of the IL-12p35 subunit and IL-4R mRNA suggested that gene expression is
      inducible, but not obviously correlated with progressive DC development.
      Expression of mRNA for a spectrum of cytokine receptors indicates that CD1a+DC
      have the potential to respond to a variety of maturational signals.

PMID- 10089132
TI  - The mitogen-activated protein kinase p38 is necesssary for interleukin 1beta
      induced monocyte chemoattractant protein 1 expression by human mesangial cells.
AB  - Mitogen-activated protein (MAP) kinases have been suggested as potential
      mediators for interleukin 1beta (IL-1beta)-induced gene activation. This study
      investigated the role of the MAP kinases p38 and ERK2 in IL-1beta-mediated
      expression of the chemokine MCP-1 by human mesangial cells. Phosphorylation of
      p38 kinase, which is necessary for activation, increased significantly after IL
      1beta treatment. p38 kinase immunoprecipitated from IL-1beta-treated cells
      phosphorylated target substrates to a greater extent than p38 kinase from
      controls. SB 203580, a selective p38 kinase inhibitor, was used to examine the
      role of p38 kinase in MCP-1 expression. SB 203580 decreased IL-1beta-induced MCP
      1 mRNA and protein levels, but did not affect MCP-1 mRNA stability. Because NF
      kappaB is necessary for MCP-1 gene expression, the effect of p38 kinase
      inhibition on IL-1beta induction of NF-kappaB was measured. SB 203580 (up to 25
      microM) had no effect on IL-1beta-induced NF-kappaB nuclear translocation or DNA
      binding activity. Our previous work showed that IL-1beta also activates the MAP
      kinase ERK2 in human mesangial cells. PD 098059, a selective inhibitor of the ERK
      activating kinase MEK1, had no effect on IL-1beta-induced MCP-1 mRNA or protein
      levels, or on IL-1beta activation of NF-kappaB. These data indicate that p38
      kinase is necessary for the induction of MCP-1 expression by IL-1beta, but is not
      involved at the level of cytoplasmic activation of NF-kappaB. In contrast, ERK2
      does not mediate IL-1beta induced MCP-1 gene expression.

PMID- 10089133
TI  - Modulation of cytokine release from mononuclear cells by prostacyclin, IL-4 and
      IL-13.
AB  - In a previous study, we reported that cicaprost, a stable prostacyclin analogue
      can inhibit the release of granulocyte-macrophage colony-stimulating factor (GM
      CSF) from activated human peripheral mononuclear blood cells (PBMCs). Since
      interleukin (IL-4) and IL-13 have been shown to inhibit the release of cytokines
      from PBMCs we tested the hypothesis that prostacyclin in combination with IL-4 or
      IL-13 can act synergistically to modulate the release of IL-10, generally
      associated with anti-inflammatory properties, and the pro-inflammatory cytokine
      tumour necrosis factor alpha (TNF-alpha). For this purpose, PBMCs were isolated
      over Ficoll, stimulated with lipopolysaccharide (LPS) and incubated in the
      presence of cicaprost, IL-4 or IL-13. There was a significant reduction in TNF
      alpha as well as IL-10 secretion from LPS-stimulated PBMCs following incubation
      with IL-4 or IL-13. In contrast, cicaprost reduced the secretion of TNF-alpha but
      led to a slight enhancement of IL-10 release from PBMCs. When LPS-activated PBMCs
      were incubated in the presence of cicaprost and IL-4 or IL-13 there was a
      selective, synergistic inhibition of the TNF-alpha release which was not observed
      for IL-10. Thus, our data suggest that prostacyclin can synergize with cytokines
      to selectively inhibit the release of pro-inflammatory cytokines from PBMCs.

PMID- 10089134
TI  - Inhibition of fibronectin-activated migration of microvascular endothelial cells
      by interleukin-1alpha, tumour necrosis factor alpha and interferon gamma.
AB  - The effect of interferon gamma (IFN) and the inflammatory cytokines tumour
      necrosis factor alpha (TNF) and interleukin 1alpha (IL-1) on micro- and
      macrovascular endothelial cell (EC) proliferation and migration was analysed.
      Whereas both micro- and macrovascular EC were growth-inhibited in response to the
      aforementioned cytokines, only microvascular EC were sensitive to TNF, IL-1 and
      IFN as inhibitors of fibronectin-activated cell migration. In addition, because
      microvascular EC play a crucial role in angiogenesis, and the formation of new
      capillaries depends upon the presence of angiogenic polypeptides, we evaluated
      the synthesis of fibroblast growth factor (FGF) type 1 and 2, Vascular
      Endothelial Growth Factor (VEGF) and Hepatocyte Growth Factor (HGF) in our
      system. Both micro- and macrovascular EC produce large amounts of FGF-2, which is
      mainly localized in the nucleus, and almost undetectable levels of FGF-1. In
      addition, the two cell types synthesize notable levels of VEGF and no HGF.
      Whether these findings are relevant to the different in vivo functions of EC
      residing different districts remains the focus of additional studies.

PMID- 10089135
TI  - Sendai virus induces various cytokines in human peripheral blood leukocytes:
      different susceptibility of cytokine molecules to low pH.
AB  - Virus infection of cell cultures induces the synthesis of various cytokines which
      can either inhibit or stimulate virus replication. The Sendai virus induces large
      quantities of biologically active interferon (IFN-alphan3) in human peripheral
      blood leukocytes (hPBL) in vitro, as well as many other cytokines. The
      supernatants of Sendai virus-infected hPBL contained biologically active IFN
      alphan3, significant amounts of immunogenic IFN-gamma, monokines (IL-1alpha, IL
      beta, TNF-alpha), lymphokines (IL-6, TNF-beta), growth factor (PDGF-AB) and small
      concentrations of IL-2 and GM-CSF. The analysis of the influence of the Sendai
      virus inactivation by lowering pH 2.0 on the cytokine concentrations showed that
      IL-1alpha, TNF-alpha, TNF-beta and IFN-gamma are susceptible to acid conditions,
      while IFN-alphan3, IL-1beta, IL-6 and IL-2 concentrations remained unchanged.

PMID- 10089136
TI  - Effects of TNF-alpha/colchicine combined treatment on Burkitt lymphoma cells:
      molecular and ultrastructural changes.
AB  - Tumour necrosis factor alpha (TNF-alpha) kills Daudi cells (Human Burkitt
      Lymphoma), inducing either necrosis or apoptosis without DNA fragmentation.
      Therefore, we were interested in studying the molecular and ultrastructural
      events occurring when the nucleus is more accessible and cells are blocked in
      mitosis, following colchicine treatment. In fact, as early as after 1 h treatment
      a typical ladder pattern was shown by means of DNA gel electrophoresis. In
      parallel the quantitative analysis of the different morphological patterns
      observed gave evidence of an increased percentage of primary necrosis after 6 h
      treatment, and a higher incidence of cells in late apoptosis as well as in
      secondary necrosis after 24 h treatment. Our findings show that Daudi cells
      respond to the combined treatment with an increased formation of micronuclei and
      nuclear alterations which follow a number of early mitochondrial changes and
      result in enhanced cell death. These data imply that TNF-alpha-induced apoptosis
      of Daudi cells can be triggered by mitochondrial changes and is somehow related
      to microtubule organization.

PMID- 10089137
TI  - HepG2 human hepatoma cells express multiple cytokine genes.
AB  - Although cytokines are known to be involved in the regulation of a variety of
      hepatocellular functions, hepatocytes themselves are generally considered only
      targets but not producers of these important mediators. In order to investigate
      whether cells of hepatocellular linages are a potential source of various
      regulatory cytokines we have estimated the multiple cytokine gene expression in
      the culture of well differentiated human HepG2 hepatoma cells using RT-PCR. Our
      findings demonstrate that HepG2 cells express mRNAs for interferon gamma (IFN
      gamma), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta
      (TGF-beta), macrophage colony-stimulating factor (M-CSF), oncostatin-M (OSM),
      intercellular adhesion molecule (ICAM-1), interleukin 4 (IL-4), IL-5, IL-7, IL
      10, IL-11, IL-12 and IL-6 receptor (IL-6R). At the same time the expression of IL
      1, IL-2, IL-3, IL-6, CD40 ligand and IL-2R genes was not detected. It was
      concluded that hepatocytes are potential producers of a variety of cytokines,
      some of them being able to regulate hepatocellular functions directly, while
      others are important regulators of leukocyte activity. Thus, on the one hand,
      hepatocytes may express autoregulatory cytokines and on the other hand, influence
      the functions of other liver cells like Kupffer, Ito or endothelial cells. Due to
      their large amount, liver parenchymal cells could be an important source of
      sytemically acting pro- and anti-inflammatory and other regulatory cytokines.

PMID- 10089138
TI  - Upregulation of endothelin 1 and its precursor by IL-1beta, TNF-alpha, and TGF
      beta in the PC3 human prostate cancer cell line.
AB  - Increasing evidence indicates that endothelin 1 (ET-1) is implicated in prostate
      tumour progression. However, data on ET-1 regulation in human prostate and
      prostate cancer cell lines are lacking. In this study, regulation of ET-1 and its
      precursor big ET-1, using PC3 cells, a human bone metastatic prostatic carcinoma
      cell line, was addressed. ET-1 and big ET-1 assays demonstrated greater secretion
      of both peptides in the presence of 10% fetal calf serum (FCS) as compared with
      0.5% FCS. Incubation of PC3 cells in the absence and presence of various
      cytokines and growth factors known to be implicated in prostate stroma-epithelium
      interactions, revealed that IL-6, FGF7/KGF and FGF2/bFGF had no effect on ET-1
      and big ET-1 secretion, whereas interleukin 1beta (IL-1beta), tumour necrosis
      factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta)
      stimulated their secretion in a concentration-dependent manner. Binding
      experiments indicated the presence of specific ET-1 receptors in PC3 cells: Kdapp
      = 1.1 x 0.2 x 10(-10)M, Bmax = 2660 +/- 390 sites/cell. Data analysis
      demonstrated the presence of only the ETA receptor subtype in PC3 cells. In
      conclusion, our results indicate that the implication of ET-1 in prostate cancer
      is likely to be mediated via paracrine/autocrine control of cell factors.

PMID- 10089139
TI  - High expression of macrophage migration inhibitory factor in the synovial tissues
      of rheumatoid joints.
AB  - Macrophage migration inhibitory factor (MIF) plays an important role in
      inflammation and immunity via autocrine/paracrine and endocrine routes. We
      examined the presence of MIF in the synovial fluids of rheumatoid arthritis (RA)
      patients. The content of MIF in the synovial fluid was quantitated by enzyme
      linked immunosorbent assay which revealed that the concentration of MIF for RA
      patients was 85. 7+/-35.2 ng/ml (mean+/-SD) (n=25). In comparison, the
      concentrations for osteoarthritis patients and normal volunteers were 19.5+/-5.3
      ng/ml (n=12) and 10.4+/-1.1 ng/ml (n=5), respectively. The expression of MIF mRNA
      and presence of MIF protein in the synovial tissues of RA were demonstrated by
      Northern blot and Western blot analyses, respectively. Immunohistochemical
      analysis revealed that positive staining was largely observed in the cytoplasm of
      infiltrating T lymphocytes, which might be the major source of MIF detected in
      the synovial fluids. The pathophysiological role of MIF in RA remains to be
      elucidated; however, the present results for the first time suggest the
      possibility that MIF is involved in the potentiation of inflammatory and
      immunological responses in rheumatoid joints.

PMID- 10089140
TI  - Reduction of tumour necrosis factor alpha expression and signalling in peripheral
      blood mononuclear cells from patients with thalassaemia or sickle cell anaemia
      upon treatment with desferrioxamine.
AB  - Recent evidence indicates that the rate of progression of the HIV-1 disease is
      significantly reduced in thalassaemia major patients upon treatment with high
      doses of desferrioxamine (DFX). The authors have previously demonstrated that in
      vitro exposure of mononuclear cells to DFX decreases the bioavailability of
      tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1
      replication. In this study, therefore, TNF-alpha bioavailability from mononuclear
      cells isolated from 10 patients with thalassaemia or sickle cell anaemia given
      DFX as compared to 10 untreated subjects has been evaluated. Evidence is
      presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05)
      by inhibiting its steady state (P<0.05) and by enhancing its inactivation through
      binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX
      treatment limits the in vivo activation of NF-kappaB, a transcription factor
      involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005).
      We conclude that TNF-alpha bioavailability and signalling are impaired in
      patients upon DFX treatment. This mechanism may contribute to delayed progression
      of the HIV-1 infection in vivo.

PMID- 10089141
TI  - Relation of ex vivo stimulated blood cytokine synthesis to post-traumatic sepsis.
AB  - The cytokine production in endotoxin stimulated blood of patients immediately
      after polytrauma with high risk for developing sepsis or multi organ failure was
      analysed. Forty patients sustaining traumatic injury with >/=317 pts according to
      the Injury Severity Score (ISS), 10 of whom developed severe sepsis (ACCP/SCCM
      conference 1992) were included in the study. Levels of interleukin 8 (IL-8), IL-6
      and tumour necrosis factor (TNF) were measured by ELISA in endotoxin-stimulated
      whole blood and IL-10 and IL-6 in serum. The allotype for the bi-allelic Nco I
      restriction length polymorphism in the TNF locus was determined for each
      patient.Two to four hours after polytrauma endotoxin-stimulated synthesis of TNF
      and IL-6 was found to be reduced in whole blood from patients compared to healthy
      donors, whereas no such differences were found for IL-8 synthesis. At this time,
      however, the patients who developed sepsis at a later stage (day 4-6) showed
      significantly (P<0.05) enhanced IL-8 synthesis in endotoxin stimulated whole
      blood in comparison to healthy donors. The IL-6 and TNF production of their blood
      was significantly enhanced compared to patients with uncomplicated recovery.
      Ninety per cent of the patients developing sepsis were of the TNFB2/TNFB2
      allotype, whereas this was the case for only 30% of the non-septic group.
      Assessment of endotoxin-stimulated cytokine synthesis may provide a prognostic
      indicator for patients at high risk for developing a sepsis syndrome.

PMID- 10089142
TI  - Detection and quantitative measurement of transforming growth factor-beta1 (TGF
      beta1) gene expression using a semi-nested competitive PCR assay.
AB  - A polymerase chain reaction (PCR) technique was optimized for detection and
      quantification of very low concentrations (down to a few molecules) of
      transforming growth factor beta1 (TGF-beta1) mRNA. The strategy involved a
      combination of a competitive PCR assay and a semi-nested PCR. In the present
      study, the semi-nested PCR technique was tested in several rat organs containing
      different concentrations of target mRNA. A control fragment for TGF-beta1 was
      used to correct for differences in amplification of various cDNA samples. TGF
      beta1 mRNA levels were also corrected according to the abundance of the
      "housekeeping" gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in the
      same samples. The differences of sensitivity among the standard (one-step) and
      semi-nested (two-step) competitive PCR assays for the detection of TGF-beta1 are
      discussed. In conclusion, the semi-nested PCR protocol provides greatly enhanced
      sensitivity over standard PCR analysis. It is a reproducible and very specific
      method for quantification of only a few molecules of TGF-beta1 mRNA in a
      background of non-target molecules.

PMID- 10089143
TI  - Population and quantitative genetics of regulatory networks.
AB  - I evolved boolean regulatory networks in a computer simulation. I varied
      mutation, recombination, the size of the network, and the number of connections
      per node. I measured the performance of networks and the heritability and
      epistasis of genetic effects. Networks of intermediate connectivity performed
      best. The distinction between metabolic and quantitative genetic additivity
      explained some of the variation in performance. Metabolic additivity describes
      the interaction between changes in a single network, whereas quantitative genetic
      additivity measures the consistency of phenotypic effect caused by gene
      substitution in randomly chosen members of the population. I analysed metabolic
      additivity by the distribution of epistatic effects of pairs of mutations in
      individual networks. I measured quantitative genetic additivity by heritability.
      Highly connected networks had greater metabolic additivity for perturbations to
      individual networks, but had lower additivity when measured by the average effect
      of a gene substitution (heritability). The lower heritability of highly connected
      nets appeared to reduce the effectiveness of recombination in searching
      evolutionary space.

PMID- 10089144
TI  - A mathematical model for outgrowth and spatial patterning of the vertebrate limb
      bud.
AB  - A new model for limb development which incorporates both outgrowth due to cell
      growth and division, and interactions between morphogens produced in the zone of
      polarizing activity (ZPA) and the apical epidermal ridge (AER) is developed and
      analysed. The numerically-computed spatio-temporal distributions of these
      morphogens demonstrate the importance of interaction between the organizing
      regions in establishing the morphogenetic terrain on which cells reside, and
      because growth is explicitly incorporated, it is found that the history of a
      cell's exposure to the morphogens depends heavily on where the cell originates in
      the early limb bud. Because the biochemical steps between morphogen(s) and gene
      activation have not been elucidated, there is no biologically-based mechanism for
      translating the spatio-temporal distributions of morphogens into patterns of gene
      expression, but several theoretically plausible functions that bridge the gap are
      suggested. For example it is shown that interpretation functions based on the
      history of a cell's exposure to the morphogens can qualitatively account for
      observed patterns of gene expression. The mathematical model and the associated
      computational algorithms are sufficiently flexible that other schemes for the
      interactions between morphogens, and their effect on the spatio-temporal pattern
      of growth and gene expression, can easily be tested. Thus an additional result of
      this work is a computational tool that can be used to explore the effects of
      various mutations and experimental interventions on the growth of the limb and
      the pattern of gene expression. In future work we will extend the model to a
      three-dimensional representation of the limb and will incorporate a more
      realistic description of the rheological properties of the tissue mass, which
      here is treated as a Newtonian fluid.

PMID- 10089145
TI  - Dynamic complexities in host-parasitoid interaction 
AB  - In the 1970s ecological research detected chaos and other forms of complex
      dynamics in simple population dynamics models, initiating a new research
      tradition in ecology. However, the investigations of complex population dynamics
      have mainly concentrated on single populations and not on higher dimensional
      ecological systems. Here we report a detailed study of the complicated dynamics
      occurring in a basic discrete-time model of host-parasitoid interaction. The
      complexities include (a) non-unique dynamics, meaning that several attractors
      coexist, (b) basins of attraction (defined as the set of the initial conditions
      leading to a certain type of an attractor) with fractal properties (pattern of
      self-similarity and fractal basin boundaries), (c) intermittency, (d)
      supertransients, (e) chaotic attractors, and (f) "transient chaos". Because of
      these complexities minor changes in parameter or initial values may strikingly
      change the dynamic behavior of the system. All the phenomena presented in this
      paper should be kept in mind when examining and interpreting the dynamics of
      ecological systems. Copyright 1999 Academic Press.

PMID- 10089146
TI  - Sperm competition. II-post-copulatory guarding 
AB  - A two round sperm competition model is analysed to determine which male strategy
      is advantageous for fertilization of a given set of eggs; guarding a particular
      female or searching for another copulation. A guarding male is one who would
      guard if he mates in the first round (which may not occur) whilst a non-guarding
      male decides on how much sperm to allocate if given the opportunity to inseminate
      a female in round one. Guarding behaviour is defined in terms of a probability of
      preventing a further insemination if challenged by a rival male. Sperm success
      with a single female obeys the "raffle principle". An evolutionarily stable
      strategy (ESS) approach is used to ascertain the best non-guarding ejaculation
      strategy. We show that for each fixed proportion of guarders in the population
      the strategies are ordered and that only a single guarding strategy need be
      considered. The model predicts that there will be evolution to either the
      guarding strategy or a single non-guarding strategy or a polymorphic combination
      of guarding and some (or all) of the non-guarding strategies. The conditions for
      coexistence to occur were shown to be rare in comparison to those necessary for a
      monomorphism. Copyright 1999 Academic Press.

PMID- 10089147
TI  - Learning foraging thresholds for lizards: an analysis of a simple learning
      algorithm 
AB  - This paper gives proof of convergence for a learning algorithm that describes how
      anoles (lizards found in the Caribbean) learn foraging threshold distance. An
      anole will pursue a prey if and only if it is within this threshold of the
      anole's perch. The learning algorithm was proposed by Roughgarden and his
      colleagues. They experimentally determined that this algorithm quickly converges
      to the foraging threshold that is predicted by optimal foraging theory. We
      provide analytic confirmation that the optimal foraging behavior as predicted by
      Roughgarden's model can be attained by a lizard that follows this simple and
      zoologically plausible rule of thumb. Copyright 1999 Academic Press.

PMID- 10089148
TI  - The application of mass and energy conservation laws in physiologically
      structured population models of heterotrophic organisms 
AB  - Rules for energy uptake, and subsequent utilization, form the basis of population
      dynamics and, therefore, explain the dynamics of the ecosystem structure in terms
      of changes in standing crops and size distributions of individuals. Mass fluxes
      are concomitant with energy flows and delineate functional aspects of ecosystems
      by defining the roles of individuals and populations. The assumption of
      homeostasis of body components, and an assumption about the general structure of
      energy budgets, imply that mass fluxes can be written as weighted sums of three
      organizing energy fluxes with the weight coefficients determined by the
      conservation law of mass. These energy fluxes are assimilation, maintenance and
      growth, and provide a theoretical underpinning of the widely applied empirical
      method of indirect calorimetry, which relates dissipating heat linearly to three
      mass fluxes: carbon dioxide production, oxygen consumption and N-waste
      production. A generic approach to the stoichiometry of population energetics from
      the perspective of the individual organism is proposed and illustrated for
      heterotrophic organisms. This approach indicates that mass transformations can be
      identified by accounting for maintenance requirements and overhead costs for the
      various metabolic processes at the population level. The theoretical background
      for coupling the dynamics of the structure of communities to nutrient cycles,
      including the water balance, as well as explicit expressions for the dissipating
      heat at the population level are obtained based on the conservation law of
      energy. Specifications of the general theory employ the Dynamic Energy Budget
      model for individuals. Copyright 1999 Academic Press.

PMID- 10089149
TI  - Reducing the number of microlocations in oligonucleotide microchip matrices by
      the application of degenerate oligonucleotides.
AB  - The application of degenerate oligonucleotides to DNA Sequencing by Hybridisation
      with Oligonucleotide Matrix (SHOM) is proposed. The use of degenerate
      oligonucleotides is regarded as an example of pooling methods that are suitable
      for various laboratory procedures requiring numerous samples to be assayed. As
      each DNA sequence coded by four letters (A, G, C, T) may be defined by two
      sequences: a sequence coded by W and S (W-weak-A or T, S-strong-G or C) and a
      sequence coded by R and Y (R-purine-A or G, Y-pirymidine-T or C), n4n -nucleotide
      sequences may be defined with the help of 2xn2sequences. In the place of the
      originally described microchip matrix composed of all possible unambiguous
      octanucleotides (4(8)=65 536) attached to the equal number of 65 536
      microlocations a matrix composed of 512 microlocations containing 256 2(8)
      degenerate octanucleotides is proposed. The matrix contains all 256 possible
      octanucleotides coded by W and S variations and all 256 possible octanucleotides
      coded by R and Y variations. The 512 256-degenerate octanucleotides allows to
      retrieve the same information as 65 536 unambiguous octanucleotides. A variant of
      the DNA sequence reconstruction method applicable to this system is presented.
      The use of degenerate oligonucleotides also gives the possibility to apply
      matrices composed of longer oligonucleotides without increasing the number of
      microlocations in matrices, which would enable increasing the length of
      unambiguously reconstructed sequence, e.g. a matrix comprising 131 072 16-mer
      oligonucleotides i.e. 65 536 65 536-fold degenerate oligonucleotide coded by W
      and S variations and 65 536 65 536-fold degenerate oligonucleotide coded by R and
      Y variations could replace one matrix comprising all possible unambiguous 16-mer
      oligonucleotides (ca. 4.3x10(9)).

PMID- 10089150
TI  - The non-monophyletic origin of the tRNA molecule.
AB  - The hypothesis that the tRNA molecule may have originated from the assembly of
      two similar RNA hairpin structures is utilised to understand the evolutionary
      period in which this molecule originated. Consistent with the exon theory of
      genes is the observation that the introns in tRNA genes are found almost
      exclusively in the anticodon loop and "stitched together" the two halves of the
      molecule, which originally may have been simply two hairpin structures and which
      can still be observed in the three-dimensional structure of tRNAs. This theory
      therefore considers these hairpin structures as minigenes on which complex
      protein synthesis may have been achieved. This in turn leads to the belief that
      the organisation of the genetic code may have been determined by use of the
      hairpin structures but not the complete tRNA molecule. In view of this, it can be
      conjectured that tRNA molecules might have been assembled only after the
      establishment of the main phyletic lines. If this is all true, then the origin of
      the tRNA molecule might have been non-monophyletic, i.e. a tRNA specific for a
      certain amino acid might have been assembled in different phyletic lines with a
      second and different hairpin structure. This leads to the belief that tRNAs
      specific for different amino acids but belonging to the same phyletic line might
      have been more similar to one another than to tRNAs specific for the same amino
      acid but belonging to different phyletic lines. This prediction seems to be
      supported by phylogenetic analysis making major use of the bootstrap technique
      performed on the tRNA sequences and by analysis already existing in the
      literature which supports the non-monophyletic origin of the tRNA molecule. The
      main conclusion of this paper is that if the tRNA molecule was assembled in the
      main phyletic lines this would imply a still rapidly evolving translation
      apparatus which, in turn, seems to imply that the last universal common ancestor
      was a progenote.

PMID- 10089151
TI  - About a three states molecular evolution model.
AB  - The Eigen model of molecular evolution has recently been reconsidered by taking
      into account the existence of non-reproducing sequences. New results obtained
      with this model are presented here: several time-scales characterize the
      population dynamics and the location of the error threshold, shifted towards
      larger values of the probability of mutation, depends on both the size of the
      population and time. Thus this model can be used to analyse extinction events.
      The distribution of individuals in sequence space beyond the threshold is also
      discussed.

PMID- 10089152
TI  - Protection and immune responses induced by attenuated Salmonella typhimurium UK-1
      strains.
AB  - We previously reported that Salmonella typhimurium SR-11 mutants with deletion
      mutations in the genes encoding adenylate cyclase (cya) and the cAMP receptor
      protein (crp) are avirulent and protective in mice. Salmonella typhimurium UK-1
      is highly virulent for chicks (oral LD50 of 3x10(3) CFU) and mice (oral LD50 of
      8.5x10(3) CFU) and is capable of lethal infections in pigs, calves and horses. We
      postulated that attenuated derivatives of this lethal strain would probably
      induce a higher level of protective immunity than achieved with attenuated
      derivatives of less virulent S. typhimurium strains such as SR11. To test this
      hypothesis, we have constructed S. typhimurium UK-1 Deltacya-12Deltacrp-11 mutant
      strain chi3985 and its virulence plasmid cured derivative chi4095 to investigate
      their avirulence and immunogenicity in mice. We found that the mutants are
      avirulent and able to induce protective immune responses in BALB/c mice. These
      mutant strains retained wild-type ability to colonize the gut associated lymphoid
      tissue but reach and persist in spleen and liver at a significantly lower level
      than the wild-type parent strain. Mice survived oral infection with >1x10(9) CFU
      of chi3985 (the equivalent to 10(5) 50% lethal doses of wild-type S. typhimurium
      UK-1) and were fully protected against challenge with 10(5)times the LD50 of the
      wild-type parent. Immunized mice developed a high level of serum IgG titre to
      Salmonella LPS and delayed-type hypersensitivity (DTH) response to S. typhimurium
      outer membrane proteins. Compared to the virulence plasmid-containing strain
      chi3985, the virulence plasmid cured DeltacyaDeltacrp mutant strain chi4095 was
      more attenuated and less protective, as some mice immunized with chi4095 died
      when challenged with the wild-type UK-1 strain. This work demonstrates that S.
      typhimurium UK-1 Deltacrp Deltacya mutant strain may be a potential live vaccine
      to induce protective immunity against Salmonella infection or to deliver foreign
      antigens to the immune system.

PMID- 10089153
TI  - Iron protoporphyrin IX-albumin complexing increases the capacity and avidity of
      its binding to the periodontopathogen Porphyromonas gingivalis.
AB  - Cells of Porphyromonas gingivalis strains W50 and WPH35 bound albumin and
      haemalbumin complexes (with 2:1 and 1:1 molar ratios of protein to iron
      protoporphyrin IX) in a concentration-dependent manner. The binding capacity for
      both haemalbumins was greater than for albumin. Scatchard analysis of binding to
      strain W50 revealed monophasic binding for albumin with an association constant
      (Ka) approximately 10(5)/M. Binding of the haemalbumin complexes was biphasic.
      The Kas of the lower-affinity binding phases were similar to that for albumin,
      whilst those for the higher-affinity binding were approximately 20-30-fold
      greater. It is concluded that both the capacity and avidity for albumin binding
      to P. gingivalis are increased following haemalbumin complex formation. This
      phenomenon would enable cells to discriminate between albumin and haem-bearing
      albumin molecules as a potential source of haem. Such binding behaviour may
      confer a nutritional and ecological advantage in the periodontal pocket or
      gingival sulcus under conditions of haem limitation.

PMID- 10089154
TI  - Identification of a fimbriae-associated haemagglutinin from Prevotella
      intermedia.
AB  - Prevotella intermedia, a putative periodontopathic microorganism, possesses
      various types of fimbriae (surface appendages). Some of these surface structures
      mediate the adherence of the organism to several mammalian erythrocytes,
      resulting in the agglutination of the erythrocytes. Prevotella intermedia
      fimbriae were solubilized and separated by preparative SDS gel electrophoresis
      followed by preparative isoelectric focusing to determine which fimbrial
      component(s) were responsible for the haemagglutinating activity exhibited by
      these bacteria. Heat treatment of isolated fractions which exhibited
      haemagglutinating activity revealed the presence of two types of
      haemagglutinating activity which were either heat sensitive or resistant.
      Analysis of isolated fractions, which exhibited haemagglutinating activity that
      were heat labile, by Tricine-sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis revealed the presence of a 3.8 kD peptide. The purified peptide
      had a pI of 4.8-5.0. Examination of fractions containing this peptide by electron
      microscopy showed the presence of fimbriae. Immunogold labelling showed that
      mouse antibodies raised against the 3.8 kD peptide bound specifically and
      extensively to P. intermedia fimbriae. It appears that this peptide is a fimbriae
      associated haemagglutinin and may represent a major constituent of the fimbriae.
      Further, fractions exhibiting haemagglutinating activity that were heat
      resistant, which were recovered at a pH of 3.5 in preparative isoelectric
      focusing of fimbrial samples, did not possess any detectable major protein bands
      as shown by analytical gel electrophoresis. However, silver stained gels for the
      detection of lipopolysaccharide (LPS) revealed the presence of LPS-like
      components in these fractions. In addition, LPS isolated from whole cells showed
      a similar electrophoretic pattern and exhibited the haemagglutinating activity
      that was heat resistant. The results of this study strongly suggest that P.
      intermedia possesses the machinery to agglutinate erythrocytes, which may be a
      contributing factor in its colonization in vivo.

PMID- 10089155
TI  - Peroxide-inducible catalase in Aeromonas salmonicida subsp. salmonicida protects
      against exogenous hydrogen peroxide and killing by activated rainbow trout,
      Oncorhynchus mykiss L., macrophages.
AB  - Aeromonas salmonicida subsp. salmonicida expresses a single cytoplasmically
      located catalase which was found to be inducible by exposure to 20 microM
      hydrogen peroxide in mid-exponential phase resulting in a 4 fold increase in
      activity. Subsequent exposure to 2 mM peroxide in late-exponential/early
      stationary phase resulted in further induction of catalase activity which
      increased to 20 fold higher levels than those found in uninduced cultures.
      Exponentially induced cultures were protected against subsequent exposure to 10
      mM peroxide which was lethal to non-induced cultures. Bacteria subjected to
      induction in mid-exponential and early-stationary phase were resistant to 100 mM
      peroxide, although viability was greatly reduced. Growth of the bacterium under
      iron-restricted conditions had no effect on the peroxide induction of catalase.
      As current evidence indicates, the latter is an iron-co-factored heme catalase,
      this result suggests that catalase induction has a high priority in the
      metabolism of iron. Furthermore, exposure to peroxide also induces expression of
      periplasmic MnSOD. A. salmonicida MT423 was resistant to normal rainbow trout
      macrophages, but was susceptible to killing by activated macrophages. However, if
      catalase was induced by prior exposure to 20 microM peroxide during mid
      exponential phase, A. salmonicida was resistant to killing by activated
      macrophages. The ability of A. salmonicida to upregulate periplasmic MnSOD and
      cytoplasmic catalase production under iron restricted conditions and low level
      peroxide (conditions expected to exist during the early stages of an infection)
      may be vital for its ability to withstand attack by phagocytic cells in vivo.

PMID- 10089156
TI  - Yersinia outer proteins (YOPS) E, K and N are antigenic but non-protective
      compared to V antigen, in a murine model of bubonic plague.
AB  - The pathogenic Yersiniae produce a range of virulence proteins, encoded by a 70
      kb plasmid, which are essential for infection, and also form part of a contact
      dependent virulence mechanism. One of these proteins, V antigen, has been shown
      to confer a high level of protection against parenteral infection with Y. pestis
      in murine models, and is considered to be a protective antigen. In this study,
      the protective efficacy of V antigen has been compared in the same model with
      that of other proteins (YopE, YopK and YopN), which are part of the contact
      dependent virulence mechanism. Mice immunised with two intraperitoneal doses of V
      antigen or each of the Yops, administered with either Alhydrogel or interleukin
      12, produced high antigen-specific serum IgG titres. As shown in previous
      studies, V+Alhydrogel was fully protective, and 5/5 mice survived a subcutaneous
      challenge with 90 or 9x10(3) LD50's of Y. pestis GB. In addition, these
      preliminary studies also showed that V+IL-12 was partially protective: 4/5 or 3/5
      mice survived a challenge with 90 or 9x10(3) LD50's, respectively. In contrast,
      none of the mice immunised with the Yops survived the challenges, and there was
      no significant delay in the mean time to death compared to mice receiving a
      control protein. These results show that using two different vaccine regimens,
      Yops E, K and N, failed to elicit protective immune responses in a murine model
      of plague, whereas under the same conditions, V antigen was fully or partially
      protective.

PMID- 10089157
TI  - Status of respiration and ATP content in arsenite resistant Leishmania mexicana
      amazonensis.
AB  - Cellular ATP and rate of respiration are important for the cell survival. We have
      analyzed both the parameters in wild type and arsenite resistant Leishmania
      mexicana amazonensis. There was no significant change observed in the rate of
      respiration and cellular ATP content between drug resistant cells (resistance to
      30 microM of sodium arsenite) and wild type cells. Further, we have tested the
      effect of higher concentrations (i.e. 100 microM and 500 microM) of sodium
      arsenite on the ATP content of the cells. An elevated level of ATP was observed
      only in wild type cells after short term exposure (2 h) to 100 microM of the
      drug, whereas, drug resistant cells initially resist with higher toxic dosage of
      drug (i.e. 500 microM) but failed to maintain the normal ATP level. In
      conclusion, respiration and ATP is not a prime event associated with drug
      resistance in Leishmania. Resistance to metals like arsenic and antimony in
      Leishmania is multifactorial events.

PMID- 10089158
TI  - Surface bound plasmin promotes migration of Streptococcus pneumoniae through
      reconstituted basement membranes.
AB  - Penetration of basement membrane is believed to be an essential step in the
      pathogenesis of bacterial meningitis. Consequently Streptococcus pneumoniae
      strains were tested for their ability to adhere to reconstituted basement
      membrane (Matrigel) and in a proceeding step penetrate this membrane by the use
      of surface activated plasmin. A majority of S. pneumoniae strains tested were
      found to adhere to reconstituted basement membrane as well as to the purified
      laminin component. Three out of seventeen strains also adhered to the collagen IV
      component. All the investigated strains also demonstrated a capacity to bind
      plasminogen with up to 42,000 plasminogen binding sites per bacterium as
      estimated by Scatchard analysis. Two strains selected for optimal adhesion and
      plasminogen binding were further tested for basement membrane penetration using a
      dual chamber model. Our data show that penetration was achieved within 3-4 h in
      the presence of plasminogen whereas without plasminogen no strain was able to
      penetrate during a 21 h incubation. The results suggest a potential role of
      surface associated plasminogen in bacterial penetration of basement membranes and
      extracellular matrix.

PMID- 10089159
TI  - Evidence of Pasteurella haemolytica linked immune complex disease in natural and
      experimental models.
AB  - The pathogenesis of bovine pneumonic pasteurellosis is not completely understood,
      and studies have not established that Pasteurella haemolytica A1 (Ph1) virulence
      is exclusively responsible for the development of acute pulmonary lesions. The
      purpose of this investigation was to determine if immune complex disease is
      involved in the pathogenesis of bovine pneumonic pasteurellosis. A retrospective
      immunohistologic study of lung tissue from natural cases of bovine pneumonic
      pasteurellosis (44) as performed, and immune complexes were observed in alveloar
      spaces and walls in 88% of these cases. To study this pathologic mechanism
      experimentally, groups of mice were immunized with purified Ph1 outer membranes
      (OMs) or sham immunized on days 0 and 14. Mice were challenged intratracheally on
      day 24 with either live Ph1 or Ph1 OMs, and pulmonary lesions were assessed 24 h
      after challenge. Placebo immunized mice developed focal infiltrates of
      neutrophils and macrophages centered around large caliber bronchi. Mice immunized
      with Ph1 OMs and challenged with live Ph1 or OMs developed severe
      bronchointerstitial pneumonia with diffuse neutrophilic infiltration, focal
      necrosis, hemorrhage and edema, that is histologically similar to bovine
      pneumonic pasteurellosis. Immunohistology revealed flocculent aggregates of IgG
      and complement positive material within alveolar spaces and walls from mice
      challenged with live Ph1, and fine granular deposits of IgG and complement
      positive material were observed lining the alveolar walls from mice challenged
      with Ph1 OMs. Immunized mice exhibited high serum IgG antibody titers to Ph1
      outer membrane proteins (OMPs). Results of this study suggest that immune complex
      disease plays a role in the pathogenesis of bovine pneumonic pasteurellosis.

PMID- 10089160
TI  - In vitro evidence of two-component system phosphorylation between the
      Mycobacterium tuberculosis TrcR/TrcS proteins.
AB  - Two-component regulatory proteins, histidine kinases and response regulators,
      function in bacteria as sensing and adaptive factors in response to a wide range
      of environmental stimuli. Conserved histidine and glycine regions of histidine
      kinase sensor proteins were used to design degenerate oligonucleotide primers for
      amplification of DNA fragments from Mycobacterium tuberculosis. Two adjacent
      genes, trcR and trcS, which encode a response regulator and a histidine kinase,
      respectively, have been identified. Full-length and truncated TrcR and TrcS
      proteins have been expressed in Escherichia coli. Difficulties in expressing
      recombinant full-length TrcS and a truncated N -terminal form of TrcS reveal that
      the transmembrane domains are toxic to E. coli. Overexpressed truncated C
      terminal transmitter domains of TrcS have been autophosphorylated in vitro and
      have transphosphorylated both the full-length recombinant TrcR protein and the N 
      terminal receiver/regulator domain of TrcR. In vitro autophosphorylation of TrcS
      requires the presence of Mn2+or Ca2+as a divalent cation cofactor and subsequent
      transphosphorylation of TrcR is evident in the presence of TrcS-phosphate and
      Ca2+. Transphosphorylation between these two proteins provides evidence that
      these M. tuberculosis genes encode functional two-component system regulatory
      proteins that are members of a signal transduction circuit.

PMID- 10089161
TI  - Cloning, expression and significance of MPT53 for identification of secreted
      proteins of Mycobacterium tuberculosis.
AB  - Based on our N -terminal amino acid sequence of MPT53 and a deduced DNA sequence,
      we searched for the corresponding gene in the Mycobacterium tuberculosis genomic
      sequence at the Sanger centre, localizing mpt53 close to mpt70 and mpt83. The
      gene was cloned and expressed, followed by purification of MPT53 to homogeneity
      from recombinant M. smegmatis culture fluid. In MPT53 there is 60 % identity with
      the active site of thioredoxin of M. tuberculosis (MPT46) with two cysteins in a
      CXXC motif, but MPT53 could not serve as an alternative substrate for thioredoxin
      reductase. Testing for IgM and IgG1 anti-MPT53 in cattle sera showed that MPT53
      is immunogenic following natural and experimental infection with M. bovis.
      Cloning of mpt53 represents cloning of the last of the 10 proteins originally
      defined as "secreted proteins" of M. tuberculosis and M. bovis based on
      determination of their "Localization index" (LI) (J Gen Microbiol 1991;137 : 875
      84). The need for a precise definition of the term "secreted protein" is
      discussed. So far we have observed full concordance between occurrence of an LI
      value indicating secretion of a protein and occurrence of a signal sequence in
      the corresponding gene. Signal sequence independent protein secretion in
      mycobacteria may occur for a limited number of proteins and remains to be
      established.

PMID- 10089162
TI  - Analysis of the Yersinia enterocolitica 0:8 V antigen for cross protectivity.
AB  - The plasmid encoded V antigen (Vag) of pathogenic Yersinia spp. is a major
      virulence factor as well as a protective immunogen. Recently, two main types of
      Vag, represented by either Yersinia enterocolitica 0:8 or Yersinia
      pseudotuberculosis, have been identified and it has been suggested, that
      antibodies generated against one type are unable to protect against Yersinia spp.
      carrying the other type. By using a recombinant Vag (rVagHis) of the Y.
      enterocolitica 0:8 type we show here, that actively immunized mice were
      completely protected against challenge with both, Y. enterocolitica 0:8 and Y.
      pseudotuberculosis serotype III. In addition, passive protection was possible
      with polyclonal rabbit anti-rVagHisIgG. However, while a single antibody dose
      (200 microgramg) was sufficient to protect against challenge with Y.
      enterocolitica 0:8, repetitive injections at intervals of 2 to 3 days were needed
      to protect against challenge with Y. pseudotuberculosis III. The apparent
      difference in protection correlated with a rapid disappearance of anti-rVagHisIgG
      from the circulation by days 3 to 4. The data therefore indicate, that expression
      of distinct types of Vag by Yersinia spp. does not necessarily exclude
      immunoprotection in mice immunized with the other type of Vag. It rather appears,
      that differences in immunoprotection between Yersinia species relate to the
      amount of cross-protective antibody. Finally, as revealed by the lack of
      complement-mediated killing and the lack of immunostaining of Yersiniae with anti
      rVagHisantibodies, evidence is provided to indicate that immunoprotection does
      not occur via opsonisation or complement lysis.

PMID- 10089163
TI  - A study of dipolar interactions and dynamic processes of water molecules in
      tendon by 1H and 2H homonuclear and heteronuclear multiple-quantum-filtered NMR
      spectroscopy.
AB  - The effect of proton exchange on the measurement of 1H-1H, 1H-2H, and 2H-2H
      residual dipolar interactions in water molecules in bovine Achilles tendons was
      investigated using double-quantum-filtered (DQF) NMR and new pulse sequences
      based on heteronuclear and homonuclear multiple-quantum filtering (MQF).
      Derivation of theoretical expressions for these techniques allowed evaluation of
      the 1H-1H and 1H-2H residual dipolar interactions and the proton exchange rate at
      a temperature of 24 degrees C and above, where no dipolar splitting is evident.
      The values obtained for these parameters at 24 degrees C were 300 and 50 Hz and
      3000 s-1, respectively. The results for the residual dipolar interactions were
      verified by repeating the above measurements at a temperature of 1.5 degrees C,
      where the spectra of the H2O molecules were well resolved, so that the 1H-1H
      dipolar interaction could be determined directly from the observed splitting.
      Analysis of the MQF experiments at 1.5 degrees C, where the proton exchange was
      in the intermediate regime for the 1H-2H dipolar interaction, confirmed the
      result obtained at 24 degrees C for this interaction. A strong dependence of the
      intensities of the MQF signals on the proton exchange rate, in the intermediate
      and the fast exchange regimes, was observed and theoretically interpreted. This
      leads to the conclusion that the MQF techniques are mostly useful for tissues
      where the residual dipolar interaction is not significantly smaller than the
      proton exchange rate. Dependence of the relaxation times and signal intensities
      of the MQF experiments on the orientation of the tendon with respect to the
      magnetic field was observed and analyzed. One of the results of the theoretical
      analysis is that, in the fast exchange regime, the signal decay rates in the MQF
      experiments as well as in the spin echo or CPMG pulse sequences (T2) depend on
      the orientation as the square of the second-rank Legendre polynomial.

PMID- 10089164
TI  - Isotope Effects on the 17O, 1H Coupling Constant and the 17O-{1H} Nuclear
      Overhauser Effect in Water.
AB  - The NMR spectra of solutions of 30% 17O-enriched H2O and D2O in nitromethane
      display the resonances of the three isotopomers H2O, HDO, and D2O. All 17O, 1H
      and 17O, 2H coupling constants and the primary and secondary isotope effects on
      J(17O, 1H) have been determined. The primary effect is -1.0 +/- 0.2 Hz and the
      secondary effect is -0.07 +/- 0.04 Hz. Using integrated intensities in the 17O
      NMR spectra, the equilibrium constant for the reaction H2O + D2O right harpoon
      over left harpoon 2HDO is found to be 3.68 +/- 0.2 at 343 K. From the relative
      integrated intensities of proton-coupled and -decoupled spectra the 17O-{1H} NOE
      is estimated for the first time, resulting in values of 0.908 and 0.945 for H2O
      and HDO, respectively. This means that dipole-dipole interactions contribute
      about 2.5% to the overall 17O relaxation rate in H2O dissolved in nitromethane.
      Copyright 1999 Academic Press.

PMID- 10089165
TI  - Time Correlations in Fluid Transport Obtained by Sequential Rephasing Gradient
      Pulses.
AB  - We present a basic experiment by which the evolution of the displacement
      probability density (propagator) of static or flowing fluid in N successive time
      intervals is obtained by single labeling, coupled with multiple rephasing events
      during the course of a pulsed field-gradient sequence. We term this type of
      sequence SERPENT: SEquential Rephasing by Pulsed field-gradients Encoding N Time
      intervals. Realizations of the SERPENT experiment for the case N = 2 which
      include spin echo, stimulated echo, and Carr-Purcell pulse sequences are
      suggested. They have in common a spatial spin-labeling of the initial
      magnetization by a gradient of area q0, followed by successive rephasing via
      gradients q1 and q2 at times t = Delta1 and t = Delta2, respectively, where q0 +
      q1 + q2 = 0. A two-dimensional Fourier transform with respect to q1 and q2 gives
      directly the joint probability density W2(R1, Delta1; R2, Delta2) for
      displacements R1 and R2 in times Delta1 and Delta2, respectively. q1 and q2 may
      be in arbitrary directions. Assuming R1 ||R2, the correlation coefficient
      rhoR1,R2 then reflects the time-history of the fluctuating velocities. The
      behavior of the cross moment <R1(Delta1). R2(Delta2)> can be obtained from either
      a full two-dimensional or a set of one-dimensional SERPENT measurements.
      Experimental results are presented for water flowing through a bed of packed
      glass beads. While Delta1 is appropriately chosen to sample the short-time
      velocity field within the system, increasing Delta2 clearly shows the loss of
      correlation when the average fluid element displacement exceeds the bead
      diameter. Copyright 1999 Academic Press.

PMID- 10089166
TI  - Magnetic Resonance Imaging of Gases: A Single-Point Ramped Imaging with T1
      Enhancement (SPRITE) Study.
AB  - A pure phase-encoding MRI technique, single-point ramped imaging with T1
      enhancement, SPRITE, is introduced for the purpose of gas phase imaging. The
      technique utilizes broadband RF pulses and stepped phase encode gradients to
      produce images, substantially free of artifacts, which are sensitive to the gas
      T1 and T&ast:2 relaxation times. Images may be acquired from gas phase species
      with transverse relaxation times substantially less than 1 ms. Methane gas
      images, 1H, were acquired in a phantom study. Sulfur hexafluoride, 19F, images
      were acquired from a gas-filled porous coral sample. High porosity regions of the
      coral are observed in both the MRI image and an X-ray image. Sensitivity and
      resolution effects due to signal modulation during the time-efficient acquisition
      are discussed. A method to increase the image sensitivity is discussed, and the
      predicted improvement is shown through 1D images of the methane gas phantom.
      Copyright 1999 Academic Press.

PMID- 10089167
TI  - Paramagnetic proton nuclear spin relaxation theory of low-symmetry complexes for
      electron spin quantum number S = 52.
AB  - A generalization of the modified Solomon-Bloembergen-Morgan (MSBM) equations has
      been derived in order to describe paramagnetic relaxation enhancement (PRE) of
      paramagnetic complexes characterized by both a transient (DeltaZFSt) and a static
      (DeltaZFSs) zero-field splitting (ZFS) interaction. The new theory includes the
      effects of static ZFS, hyperfine coupling, and angular dependence and is
      presented for the case of electron spin quantum number S = 52, for example,
      Mn(II) and Fe(III) complexes. The model gives the difference from MSBM theory in
      terms of a correction term delta which is given in closed analytical form. The
      theory may be important in analyzing the PRE of proton spin-lattice relaxation
      dispersion measurements (NMRD profiles) of low-symmetry aqua-metal complexes
      which are likely to be formed upon transition metal ions associated with charged
      molecular surfaces of biomacromolecules. The theory has been implemented with a
      computer program which calculates solvent water proton T1 NMRD profiles using
      both MSBM and the new theory.

PMID- 10089168
TI  - HCCCH experiment for through-bond correlation of thymine resonances in 13C
      labeled DNA oligonucleotides.
AB  - Application of heteronuclear magnetic resonance pulse methods to 13C, 15N-labeled
      nucleic acids is important for the accurate structure determination of larger RNA
      and DNA oligonucleotides and protein-nucleic acid complexes. These methods have
      been applied primarily to RNA, due to the availability of labeled samples. The
      two major differences between DNA and RNA are at the C2' of the ribose and
      deoxyribose and the additional methyl group on thymine versus uracil. We have
      enzymatically synthesized a 13C,15N-labeled 32 base DNA oligonucleotide that
      folds to form an intramolecular triplex. We present two- and three-dimensional
      versions of a new HCCCH-TOCSY experiment that provides intraresidue correlation
      between the thymine H6 and methyl resonances via the intervening carbons (H6-C6
      C5-Cme-Hme).

PMID- 10089169
TI  - Effect of exercise on the creatine resonances in 1H MR spectra of human skeletal
      muscle.
AB  - 1H MR spectra of human muscles were recorded before, during, and after fatiguing
      exercise. In contrast to expectations, it was found that the spectral
      contributions of creatine/phosphocreatine (Cr/PCr) were subject to change as a
      function of exercise. In particular, the dipolar-coupled methylene protons of
      Cr/PCr were found to be reduced in intensity in proportion to the co-registered
      PCr levels. Recovery after exercise and behavior under ischemic conditions
      provide further evidence to suggest that the contributions of the CH2 protons of
      Cr/PCr to 1H MR spectra of human muscle in vivo reflect PCr rather than Cr
      levels. Variation of experimental parameters showed that this effect is not due
      to a trivial change in relaxation times. At present it can only be speculated
      about why the Cr resonances have reduced NMR visibility. If temporary binding to
      macromolecules should be involved, the free Cr concentration-important for
      equilibrium calculations of the creatine kinase reaction-might be different from
      what was previously assumed.

PMID- 10089170
TI  - Spin Echo Analysis of Restricted Diffusion under Generalized Gradient Waveforms:
      Planar, Cylindrical, and Spherical Pores with Wall Relaxivity.
AB  - A simple matrix formalism presented by Callaghan [J. Magn. Reson. 129, 74-84
      (1997)], and based on the multiple propagator approach of Caprihan et al. [J.
      Magn. Reson. A 118, 94-102 (1996)], allows for the calculation of the echo
      attenuation, E(q), in spin echo diffusion experiments, for practically all
      gradient waveforms. We have extended the method to the treatment of restricted
      diffusion in parallel plate, cylindrical, and spherical geometries, including the
      effects of fluid-surface interactions. In particular, the q-space coherence
      curves are presented for the finite-width gradient pulse PGSE experiment and the
      results of the matrix calculations compare precisely with published computer
      simulations. It is shown that the use of long gradient pulses (delta
      approximately a2/D) create the illusion of smaller pores if a narrow pulse
      approximation is assumed, while ignoring the presence of significant wall
      relaxation can lead to both an underestimation of the pore dimensions and a
      misidentification of the pore geometry. Copyright 1999 Academic Press.

PMID- 10089171
TI  - A tunable reentrant resonator with transverse orientation of electric field for
      in vivo EPR spectroscopy.
AB  - There has been a need for development of microwave resonator designs optimized to
      provide high sensitivity and high stability for EPR spectroscopy and imaging
      measurements of in vivo systems. The design and construction of a novel reentrant
      resonator with transversely oriented electric field (TERR) and rectangular sample
      opening cross section for EPR spectroscopy and imaging of in vivo biological
      samples, such as the whole body of mice and rats, is described. This design with
      its transversely oriented capacitive element enables wide and simple setting of
      the center frequency by trimming the dimensions of the capacitive plate over the
      range 100-900 MHz with unloaded Q values of approximately 1100 at 750 MHz, while
      the mechanical adjustment mechanism allows smooth continuous frequency tuning in
      the range +/-50 MHz. This orientation of the capacitive element limits the
      electric field based loss of resonator Q observed with large lossy samples, and
      it facilitates the use of capacitive coupling. Both microwave performance data
      and EPR measurements of aqueous samples demonstrate high sensitivity and
      stability of the design, which make it well suited for in vivo applications.

PMID- 10089172
TI  - High-speed data acquisition system and receiver configurations for time-domain
      radiofrequency electron paramagnetic resonance spectroscopy and imaging.
AB  - Design strategies, system configuration, and operation of a dual-channel data
      acquisition system for a radiofrequency (RF) time-domain electron paramagnetic
      resonance (EPR) spectrometer/imager operating at 300 MHz are described. This
      system wasconfigured to incorporate high-speed analog-to-digital conversion (ADC)
      and summation capabilities with both internal and external triggering via GPIB
      interface. The sampling rate of the ADC is programmable up to a maximum of 1 GS/s
      when operating in a dual-channel mode or 2 GS/s when the EPR data are collected
      in a single-channel mode. By using high-speed flash ADCs, a pipelined 8-bit
      adder, and a 24-bit accumulator, a repetition rate of 230 kHz is realized to sum
      FIDs of 4096 points. The record length is programmable up to a maximum of 8K
      points and a large number of FIDs (2(24)) can be summed without overflow before
      the data can be transferred to a host computer via GPIB interface for further
      processing. The data acquisition system can operate in a two-channel (quadrature)
      receiver mode for the conventional mixing to baseband. For detection using the
      single-channel mode, the resonance signals around the center frequency of 300 MHz
      were mixed with a synchronized local oscillator of appropriate frequency leading
      to an intermediate frequency (IF) which is sampled at a rate of 2 GS/s.
      Comparison of quadrature-mode and an IF-mode operation for EPR detection is
      presented by studying the FID signal intensity across a bandwidth of 10 MHz and
      as a function of transmit RF power. Imaging of large-sized phantoms accommodated
      in appropriately sized resonators indicates that IF-mode operation can be used to
      obtain distortion-free images in resonators of size 50 mm diameter and 50 mm
      length.

PMID- 10089173
TI  - Spin concentration in a possible ESR dosimeter: An electron spin echo study on X
      irradiated ammonium tartrate.
AB  - Several single crystals and powder samples of ammonium tartrate, recently
      proposed as a possible ESR dosimeter, have been X-irradiated with different
      doses. The total radical concentration has been determined by quantitative cw
      ESR, by comparison with a standard. The samples have been studied by electron
      spin echo spectroscopy. The two-pulse echo decay has been obtained and simulated
      by a single exponential function for different values of the microwave power of
      the pulses and for different pulse lengths. The dependence of the phase memory
      time TM on the microwave power has been exploited to get information on the
      contribution of the instantaneous diffusion to spin dephasing. At room
      temperature in the range of radical concentrations of 10(18)-10(19) spins/cm3 the
      instantaneous diffusion is the dominant spin dephasing mechanism. The linear
      dependence of the instantaneous diffusion on the total concentration of the
      radicals is in agreement with the theory. From the latter result we conclude that
      the average radical-radical distance corresponds to a random distribution of the
      radicals in the matrix. A simple method of measuring the radical concentration by
      the ESE decays in powder samples of irradiated ammonium tartrate is described.

PMID- 10089174
TI  - A Pulsed Field Gradient Spin-Echo Method for Diffusion Measurements in the
      Presence of Internal Gradients.
AB  - Over the past decade several pulsed field gradient stimulated-echo methods have
      been presented for diffusion measurements in heterogeneous media. These methods
      have reduced or eliminated the coupling between the applied magnetic field
      gradient and a constant internal magnetic field gradient caused by susceptibility
      changes throughout the sample. For many research purposes the z-storage delay
      between the second and third pi/2 RF pulse has been included in order to increase
      the decay of the echo attenuation to an appropriate level and to increase the
      signal-to-noise ratio by avoiding T2 relaxation of the magnetization in parts of
      the pulse sequence. For these reasons a stimulated-echo method has been applied
      instead of a spin-echo method. When studying systems where it is necessary to
      keep the duration of the pulse sequence at a minimum, and one is not dependent on
      using z-storage time to increase the echo attenuation or to study diffusion as a
      function of observation time, a spin-echo method should be chosen. Here we
      propose a bipolar pulsed field gradient spin-echo method which is well suited to
      this purpose, and preliminary diffusion measurements are presented as
      illustration. Copyright 1999 Academic Press.

PMID- 10089175
TI  - Corrected equations for susceptibility-induced T2-shortening.
AB  - Local field gradients created by paramagnetic entities shorten water proton
      relaxation times, particularly T2. This "novel" relaxation mechanism, now known
      as susceptibility-induced relaxation, was described twenty years ago by Gueron,
      and later extended by others to superparamagnetic particles which have a much
      larger magnetization. Unfortunately, because of subtle but significant errors,
      those results are valid only in the strict zero-field limit. These errors are
      corrected in the present article, and new versions of the relaxation equations
      are presented. The correction is shown to be significant, not only for transverse
      and longitudinal relaxation in aqueous superparamagnetic colloids, where the
      "Gueron" effect is known to be important, but even in some cases for transverse
      paramagnetic relaxation.

PMID- 10089177
TI  - Measurement of Magnitude and Sign of Heteronuclear Coupling Constants in
      Transition Metal Complexes.
AB  - Sets of specifically tailored E.COSY-type correlation experiments and double
      quantum/zero-quantum (DQ/ZQ) experiments are presented which enable the
      determination of sign and size of small heteronuclear coupling constants across
      the metal center of transition metal complexes. For the octahedrally coordinated
      complexes, [Ru(TPM)(H)(CO)(PPh3)]+[BF4]- (1) and [Ir(TPM)(H)(CO)(CO2CH3)]+[BF4]-
      (2), 14 of 15 and 15 of 15 possible two-bond scalar coupling constants across the
      metal center were measured, respectively, using 15N and 15N/13C enriched samples
      (TPM = tris(1-pyrazolyl)methane)). The reduced coupling constants 2KX-M-Y = 4pi2
      2J/(hgammaXgammaY) were found to be positive when the coupled nuclei X and Y were
      trans with respect to the metal center, and negative when the coupled nuclei were
      in cis position. The validity of this sign rule was verified for JCC, JNN, JPN,
      JPC, JCN, JHP, JHC, and JHN couplings. Idiosyncracies associated with 2D NMR
      spectra for the sign determination of coupling constants with 15N which lead to
      corrections for the signs of JHN, JPN, and JCN couplings reported previously are
      discussed. Copyright 1999 Academic Press.

PMID- 10089176
TI  - Simplified multiplet pattern HSQC-TOCSY experiment for accurate determination of
      long-range heteronuclear coupling constants.
AB  - A new two-dimensional pulse sequence for accurately determining heteronuclear
      coupling constants is presented. It is derived from HSQC and HECADE techniques
      with B0 gradient coherence selection. The main feature of the proposed method is
      spectra with only one component of the IS doublet; i.e., the final result is
      equivalent to a selective broadband excitation of either Salpha or Sbeta spin
      states and a preservation of these states during the entire experiment. The
      effect is obtained by an appropriate combination of in- and antiphase coherences.
      It is demonstrated that heteronuclear single-bond as well as long-range coupling
      constants and their relative signs are readily evaluated. The proposed sequence
      is equally or less sensitive to a variation of heteronuclear one-bond couplings
      than previously published, closely related sequences. The new method is applied
      to a peptide sample for determination of 3JN, Hbeta.

PMID- 10089178
TI  - Artifacts introduced by zero order phase correction in proton NMR spectroscopy
      and a method of elimination by phase filtering.
AB  - In in-vivo applications of proton NMR spectroscopic imaging, an oscillatory
      "ringing" artifact has been observed in some of the spectra. The source of this
      artifact was found to be the presence of a harmonic "beating" effect in the
      amplitude of the water reference free induction decay (FID) which was used for
      zero order phase correction for B0 inhomogeneity and eddy current compensation.
      The source of the beats was found to be the presence of distinct populations of
      spins resonating at slightly different frequencies. When the common method of
      zero order phase correction was implemented using such an FID, the resulting
      phase-corrected, water-suppressed spectra displayed ringing. Examination of the
      unwrapped phase correction angle revealed unexpected jumps in phase at points in
      time corresponding to nodes in the amplitude of the FID. Low-pass filtering of
      the phase correction angle of the reference FID was found to smooth out these
      unanticipated phase jumps. When used as a reference for phase correction, the
      filtered phase information gave a phase-corrected, water-suppressed spectrum free
      from ringing.

PMID- 10089179
TI  - Sensitivity-enhanced sim-CT HMQC PFG-HBHA(CO)NH and PFG-CBCA(CO)NH triple
      resonance experiments.
AB  - Short transverse relaxation times of Calpha and Cbeta single-quantum coherences
      reduce the sensitivity of triple-resonance experiments involving transfers of
      Calpha/Cbeta or Halpha/Hbeta coherences. Multiple-quantum line-narrowing
      techniques improve the relaxation properties of 13C coherences, thereby
      increasing the sensitivity of the experiment. In the present work, we describe
      PFG-CBCA(CO)NH and PFG-HBHA(CO)NH experiments that utilize heteronuclear multiple
      quantum coherences in a simultaneous constant-time period to obtain completely
      decoupled spectra with improved sensitivity. Results indicate that approximately
      30% of cross peaks show an average enhancement of approximately 15% in the
      CBCA(CO)NH experiment. In the related HBHA(CO)NH experiment, approximately 97% of
      the cross peaks show an average enhancement of approximately 40%.

PMID- 10089180
TI  - NMR experiments for the study of photointermediates: application to the
      photoactive yellow protein.

PMID- 10089181
TI  - Separate quantification of doubly and singly 13C-labeled metabolites by HSQC
      filtered J spectroscopy.
AB  - NMR detection of multiply labeled compounds in biological samples is often used
      to follow metabolic pathways. Detection of protons bound to 13C atoms offers a
      more sensitive approach than direct 13C detection, but generally results in the
      loss of carbon-carbon coupling information. We have modified an HSQC sequence to
      refocus the carbon chemical shifts in order to obtain a proton-correlated 13C
      homonuclear J spectrum, which allows us to measure singly and doubly labeled
      compounds in the same spectrum.

PMID- 10089183
TI  - A comparison of three months of anticoagulation with extended anticoagulation for
      a first episode of idiopathic venous thromboembolism.
AB  - BACKGROUND: Patients who have a first episode of venous thromboembolism in the
      absence of known risk factors for thrombosis (idiopathic thrombosis) are often
      treated with anticoagulant therapy for three months. Such patients may benefit
      from longer treatment, however, because they appear to have an increased risk of
      recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind
      study, we randomly assigned patients who had completed 3 months of anticoagulant
      therapy for a first episode of idiopathic venous thromboembolism to continue
      receiving warfarin, with the dose adjusted to achieve an international normalized
      ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was
      to determine the effects of extended anticoagulant therapy on rates of recurrent
      symptomatic venous thromboembolism and bleeding. RESULTS: A prespecified interim
      analysis of efficacy led to the early termination of the trial after 162 patients
      had been enrolled and followed for an average of 10 months. Of 83 patients
      assigned to continue to receive placebo, 17 had a recurrent episode of venous
      thromboembolism (27.4 percent per patient-year), as compared with 1 of 79
      patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001).
      Warfarin resulted in a 95 percent reduction in the risk of recurrent venous
      thromboembolism (95 percent confidence interval, 63 to 99 percent). Three
      patients assigned to the warfarin group had nonfatal major bleeding (two had
      gastrointestinal bleeding and one genitourinary bleeding), as compared with none
      of those assigned to the placebo group (3.8 vs. 0 percent per patient-year,
      P=0.09). CONCLUSIONS: Patients with a first episode of idiopathic venous
      thromboembolism should be treated with anticoagulant agents for longer than three
      months.

PMID- 10089184
TI  - Extended lymph-node dissection for gastric cancer.
AB  - BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but
      it is unclear whether this operation should include an extended (D2) lymph-node
      dissection, as recommended by the Japanese medical community, or a limited (D1)
      dissection. We conducted a randomized trial in 80 Dutch hospitals in which we
      compared D1 with D2 lymph-node dissection for gastric cancer in terms of
      morbidity, postoperative mortality, long-term survival, and cumulative risk of
      relapse after surgery. METHODS: Between August 1989 and July 1993, a total of 996
      patients entered the study. Of these patients, 711 (380 in the D1 group and 331
      in the D2 group) underwent the randomly assigned treatment with curative intent,
      and 285 received palliative treatment. The procedures for quality control
      included instruction and supervision in the operating room and monitoring of the
      pathological results. RESULTS: Patients in the D2 group had a significantly
      higher rate of complications than did those in the D1 group (43 percent vs. 25
      percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P=
      0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year
      survival rates were similar in the two groups: 45 percent for the D1 group and 47
      percent for the D2 group (95 percent confidence interval for the difference, -9.6
      percent to +5.6 percent). The patients who had R0 resections (i.e., who had no
      microscopical evidence of remaining disease), excluding those who died
      postoperatively, had cumulative risks of relapse at five years of 43 percent with
      D1 dissection and 37 percent with D2 dissection (95 percent confidence interval
      for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS: Our results in
      Dutch patients do not support the routine use of D2 lymph-node dissection in
      patients with gastric cancer.

PMID- 10089185
TI  - Passive smoking and the risk of coronary heart disease--a meta-analysis of
      epidemiologic studies.
AB  - BACKGROUND: The effect of passive smoking on the risk of coronary heart disease
      is controversial. We conducted a meta-analysis of the risk of coronary heart
      disease associated with passive smoking among nonsmokers. METHODS: We searched
      the Medline and Dissertation Abstracts Online data bases and reviewed citations
      in relevant articles to identify 18 epidemiologic (10 cohort and 8 case-control)
      studies that met prestated inclusion criteria. Information on the designs of the
      studies, the characteristics of the study subjects, exposure and outcome
      measures, control for potential confounding factors, and risk estimates was
      abstracted independently by three investigators using a standardized protocol.
      RESULTS: Overall, nonsmokers exposed to environmental smoke had a relative risk
      of coronary heart disease of 1.25 (95 percent confidence interval, 1.17 to 1.32)
      as compared with nonsmokers not exposed to smoke. Passive smoking was
      consistently associated with an increased relative risk of coronary heart disease
      in cohort studies (relative risk, 1.21; 95 percent confidence interval, 1.14 to
      1.30), in case-control studies (relative risk, 1.51; 95 percent confidence
      interval, 1.26 to 1.81), in men (relative risk, 1.22; 95 percent confidence
      interval, 1.10 to 1.35), in women (relative risk, 1.24; 95 percent confidence
      interval, 1.15 to 1.34), and in those exposed to smoking at home (relative risk,
      1.17; 95 percent confidence interval, 1.11 to 1.24) or in the workplace (relative
      risk, 1.11; 95 percent confidence interval, 1.00 to 1.23). A significant dose
      response relation was identified, with respective relative risks of 1.23 and 1.31
      for nonsmokers who were exposed to the smoke of 1 to 19 cigarettes per day and
      those who were exposed to the smoke of 20 or more cigarettes per day, as compared
      with nonsmokers not exposed to smoke (P=0.006 for linear trend). CONCLUSIONS:
      Passive smoking is associated with a small increase in the risk of coronary heart
      disease. Given the high prevalence of cigarette smoking, the public health
      consequences of passive smoking with regard to coronary heart disease may be
      important.

PMID- 10089186
TI  - Images in clinical medicine. Gastric tumor discovered by chest radiography.

PMID- 10089188
TI  - Preoperative pulmonary evaluation.

PMID- 10089187
TI  - Views of managed care--a survey of students, residents, faculty, and deans at
      medical schools in the United States.
AB  - BACKGROUND AND METHODS: Views of managed care among academic physicians and
      medical students in the United States are not well known. In 1997, we conducted a
      telephone survey of a national sample of medical students (506 respondents),
      residents (494), faculty members (728), department chairs (186), directors of
      residency training in internal medicine and pediatrics (143), and deans (105) at
      U.S. medical schools to determine their experiences in and perspectives on
      managed care. The overall rate of response was 80.1 percent. RESULTS: Respondents
      rated their attitudes toward managed care on a 0-to-10 scale, with 0 defined as
      "as negative as possible" and 10 as "as positive as possible." The expressed
      attitudes toward managed care were negative, ranging from a low mean (+/-SD)
      score of 3.9+/-1.7 for residents to a high of 5.0+/-1.3 for deans. When asked
      about specific aspects of care, fee-for-service medicine was rated better than
      managed care in terms of access (by 80.2 percent of respondents), minimizing
      ethical conflicts (74.8 percent), and the quality of the doctor-patient
      relationship (70.6 percent). With respect to the continuity of care, 52.0 percent
      of respondents preferred fee-for-service medicine, and 29.3 percent preferred
      managed care. For care at the end of life, 49.1 percent preferred fee-for-service
      medicine, and 20.5 percent preferred managed care. With respect to care for
      patients with chronic illness, 41.8 percent preferred fee-for-service care, and
      30.8 percent preferred managed care. Faculty members, residency-training
      directors, and department chairs responded that managed care had reduced the time
      they had available for research (63.1 percent agreed) and teaching (58.9 percent)
      and had reduced their income (55.8 percent). Overall, 46.6 percent of faculty
      members, 26.7 percent of residency-training directors, and 42.7 percent of
      department chairs reported that the message they delivered to students about
      managed care was negative. CONCLUSIONS: Negative views of managed care are
      widespread among medical students, residents, faculty members, and medical school
      deans.

PMID- 10089189
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 9-1999. A 75-year-old woman with hydrocephalus and pleocytosis.

PMID- 10089190
TI  - Venous thrombosis as a chronic disease.

PMID- 10089191
TI  - Lymph-node dissection for gastric cancer.

PMID- 10089192
TI  - Passive smoking, coronary heart disease, and meta-analysis.

PMID- 10089194
TI  - A computer-driven approach to PCR-based differential screening, alternative to
      differential display.
AB  - MOTIVATION: Polymerase chain reaction (PCR)-based RNA fingerprinting is a
      powerful tool for the isolation of differentially expressed genes in studies of
      neoplasia, differentiation or development. Arbitrarily primed RNA fingerprinting
      is capable of targeting coding regions of genes, as opposed to differential
      display techniques, which target 3' non-coding cDNA. In order to be of general
      use and to permit a systematic survey of differential gene expression, RNA
      fingerprinting has to be standardized and a number of highly efficient and
      selective arbitrary primers must be identified. RESULTS: We have applied a
      rational approach to generate a representative panel of high-efficiency
      oligonucleotides for RNA fingerprinting studies, which display marked affinity
      for coding portions of known genes and, as shown by preliminary results, of novel
      ones. The choice of oligonucleotides was driven by computer simulations of RNA
      fingerprinting reverse transcriptase (RT)-PCR experiments, performed on two
      custom-generated, non-redundant nucleotide databases, each containing the
      complete collection of deposited human or murine cDNAs. The simulation approach
      and experimental protocol proposed here permit the efficient isolation of coding
      cDNA fragments from differentially expressed genes. AVAILABILITY: Freely
      available on request from the authors. CONTACT: fesce.riccardo@hsr.it

PMID- 10089195
TI  - Establishing a method of vector contamination identification in database
      sequences.
AB  - MOTIVATION: The nucleotide sequence databases are invaluable tools both for the
      private and the academic research communities, from the retrieval of sequences to
      homology searching. Several issues related to data quality, such as the existence
      of sequencing artifacts and errors, are facing the databases. We investigated a
      major source of these errors, i.e. the presence of vector-contaminated sequences.
      RESULTS: Using a panel of 180 vector polylinker sequences, we found 0.36% or 3029
      vector-matching sequences in GenBank Release 95-96, with an average vector
      matching length of 72 nucleotides. The number of vector-contaminated sequences
      has been growing with the database; however, the percent contamination has
      remained approximately constant at an average of 0.28% from 1982 to 1996.
      AVAILABILITY: Access to the database of vector polylinker sequences via sequence
      similarity searching is available at http://seqsim.ncgr.org/vector/ CONTACT:
      gas@molinfo.com

PMID- 10089196
TI  - A RAPID algorithm for sequence database comparisons: application to the
      identification of vector contamination in the EMBL databases.
AB  - MOTIVATION: Word-matching algorithms such as BLAST are routinely used for
      sequence comparison. These algorithms typically use areas of matching words to
      seed alignments which are then used to assess the degree of sequence similarity.
      In this paper, we show that by formally separating the word-matching and sequence
      alignment process, and using information about word frequencies to generate
      alignments and similarity scores, we can create a new sequence-comparison
      algorithm which is both fast and sensitive. The formal split between word
      searching and alignment allows users to select an appropriate alignment method
      without affecting the underlying similarity search. The algorithm has been used
      to develop software for identifying entries in DNA sequence databases which are
      contaminated with vector sequence. RESULTS: We present three algorithms, RAPID,
      PHAT and SPLAT, which together allow vector contaminations to be found and
      assessed extremely rapidly. RAPID is a word search algorithm which uses
      probabilities to modify the significance attached to different words; PHAT and
      SPLAT are alignment algorithms. An initial implementation has been shown to be
      approximately an order of magnitude faster than BLAST. The formal split between
      word searching and alignment not only offers considerable gains in performance,
      but also allows alignment generation to be viewed as a user interface problem,
      allowing the most useful output method to be selected without affecting the
      underlying similarity search. Receiver Operator Characteristic (ROC) analysis of
      an artificial test set allows the optimal score threshold for identifying vector
      contamination to be determined. ROC curves were also used to determine the
      optimum word size (nine) for finding vector contamination. An analysis of the
      entire expressed sequence tag (EST) subset of EMBL found a contamination rate of
      0.27%. A more detailed analysis of the 50 000 ESTs in est10.dat (an EST subset of
      EMBL) finds an error rate of 0.86%, principally due to two large-scale projects.
      AVAILABILITY: A Web page for the software exists at
      http://bioinf.man.ac.uk/rapid, or it can be downloaded from
      ftp://ftp.bioinf.man.ac.uk/RAPID CONTACT: crispin@cs.man.ac.uk

PMID- 10089197
TI  - Combining many multiple alignments in one improved alignment.
AB  - MOTIVATION: The fact that the multiple sequence alignment problem is of high
      complexity has led to many different heuristic algorithms attempting to find a
      solution in what would be considered a reasonable amount of computation time and
      space. Very few of these heuristics produce results that are guaranteed always to
      lie within a certain distance of an optimal solution (given a measure of quality,
      e.g. parsimony). Most practical heuristics cannot guarantee this, but
      nevertheless perform well for certain cases. An alignment, obtained with one of
      these heuristics and with a bad overall score, is not unusable though, it might
      contain important information on how substrings should be aligned. This paper
      presents a method that extracts qualitatively good sub-alignments from a set of
      multiple alignments and combines these into a new, often improved alignment. The
      algorithm is implemented as a variant of the traditional dynamic programming
      technique. RESULTS: An implementation of ComAlign (the algorithm that combines
      multiple alignments) has been run on several sets of artificially generated
      sequences and a set of 5S RNA sequences. To assess the quality of the alignments
      obtained, the results have been compared with the output of MSA 2.1 (Gupta et
      al., Proceedings of the Sixth Annual Symposium on Combinatorial Pattern Matching,
      1995; Kececioglu et al., http://www.techfak.uni-bielefeld.
      de/bcd/Lectures/kececioglu.html, 1995). In all cases, ComAlign was able to
      produce a solution with a score comparable to the solution obtained by MSA. The
      results also show that ComAlign actually does combine parts from different
      alignments and not just select the best of them. AVAILABILITY: The C source code
      (a Smalltalk version is being worked on) of ComAlign and the other programs that
      have been implemented in this context are free and available on WWW
      (http://www.daimi.au.dk/ ocaprani). CONTACT: klaus@bucka-lassen.dk;
      jotun@pop.bio.au.dk;ocaprani@daimi.au.dk

PMID- 10089198
TI  - FORESST: fold recognition from secondary structure predictions of proteins.
AB  - MOTIVATION: A method for recognizing the three-dimensional fold from the protein
      amino acid sequence based on a combination of hidden Markov models (HMMs) and
      secondary structure prediction was recently developed for proteins in the Mainly
      Alpha structural class. Here, this methodology is extended to Mainly-Beta and
      Alpha-Beta class proteins. Compared to other fold recognition methods based on
      HMMs, this approach is novel in that only secondary structure information is
      used. Each HMM is trained from known secondary structure sequences of proteins
      having a similar fold. Secondary structure prediction is performed for the amino
      acid sequence of a query protein. The predicted fold of a query protein is the
      fold described by the model fitting the predicted sequence the best. RESULTS:
      After model cross-validation, the success rate on 44 test proteins covering the
      three structural classes was found to be 59%. On seven fold predictions performed
      prior to the publication of experimental structure, the success rate was 71%. In
      conclusion, this approach manages to capture important information about the fold
      of a protein embedded in the length and arrangement of the predicted helices,
      strands and coils along the polypeptide chain. When a more extensive library of
      HMMs representing the universe of known structural families is available (work in
      progress), the program will allow rapid screening of genomic databases and
      sequence annotation when fold similarity is not detectable from the amino acid
      sequence. AVAILABILITY: FORESST web server at http://absalpha.dcrt.nih.gov:8008/
      for the library of HMMs of structural families used in this paper. FORESST web
      server at http://www.tigr.org/ for a more extensive library of HMMs (work in
      progress). CONTACT: valedf@tigr.org; munson@helix.nih.gov; garnier@helix.nih.gov

PMID- 10089199
TI  - The hydrophobic cores of proteins predicted by wavelet analysis.
AB  - MOTIVATION: In the process of protein construction, buried hydrophobic residues
      tend to assemble in a core of a protein. Methods used to predict these cores
      involve use or no use of sequential alignment. In the case of a close homology,
      prediction was more accurate if sequential alignment was used. If the homology
      was weak, predictions would be unreliable. A hydrophobicity plot involving the
      hydropathy index is useful for purposes of prediction, and smoothing is
      essential. However, the proposed methods are insufficient. We attempted to
      predict hydrophobic cores with a low frequency extracted from the hydrophobicity
      plot, using wavelet analysis. RESULTS: The cores were predicted at a rate of
      68.7%, by cross-validation. Using wavelet analysis, the cores of non-homologous
      proteins can be predicted with close to 70% accuracy, without sequential
      alignment. AVAILABILITY: The program used in this study is available from
      Intergalactic Reality (http://www.intergalact.com). CONTACT: hirakawa@grt.kyushu
      u.ac.jp, kuhara@grt.kyushu-u.ac.jp

PMID- 10089200
TI  - HICLAS: a taxonomic database system for displaying and comparing biological
      classification and phylogenetic trees.
AB  - MOTIVATION: Numerous database management systems have been developed for
      processing various taxonomic data bases on biological classification or
      phylogenetic information. In this paper, we present an integrated system to deal
      with interacting classifications and phylogenies concerning particular taxonomic
      groups. RESULTS: An information-theoretic view (taxon view) has been applied to
      capture taxonomic concepts as taxonomic data entities. A data model which is
      suitable for supporting semantically interacting dynamic views of hierarchic
      classifications and a query method for interacting classifications have been
      developed. The concept of taxonomic view and the data model can also be expanded
      to carry phylogenetic information in phylogenetic trees. We have designed a
      prototype taxonomic database system called HICLAS (HIerarchical CLAssification
      System) based on the concept of taxon view, and the data models and query methods
      have been designed and implemented. This system can be effectively used in the
      taxonomic revisionary process, especially when databases are being constructed by
      specialists in particular groups, and the system can be used to compare
      classifications and phylogenetic trees. AVAILABILITY: Freely available at the WWW
      URL: http://aims.cps.msu.edu/hiclas/ CONTACT: pramanik@cps.msu.edu;
      lotus@wipm.whcnc.ac.cn

PMID- 10089201
TI  - A proposal for a standard CORBA interface for genome maps.
AB  - MOTIVATION: The scientific community urgently needs to standardize the exchange
      of biological data. This is helped by the use of a common protocol and the
      definition of shared data structures. We have based our standardization work on
      CORBA, a technology that has become a standard in the past years and allows
      interoperability between distributed objects. RESULTS: We have defined an IDL
      specification for genome maps and present it to the scientific community. We have
      implemented CORBA servers based on this IDL to distribute RHdb and HuGeMap maps.
      The IDL will co-evolve with the needs of the mapping community. AVAILABILITY: The
      standard IDL for genome maps is available at http://
      corba.ebi.ac.uk/RHdb/EUCORBA/MapIDL.htm l. The IORs to browse maps from
      Infobiogen and EBI are at http://www.infobiogen.fr/services/Hugemap/IOR and
      http://corba.ebi.ac.uk/RHdb/EUCORBA/IOR CONTACT: manu@infobiogen.fr,
      tome@ebi.ac.uk

PMID- 10089202
TI  - An extensive list of genes that produce alternative transcripts in the mouse.
AB  - SUMMARY: A single gene can generate multiple transcribed gene products. An
      extensive list of alternatively transcribed mouse genes has been generated, and
      is publicly available from http://www.informatics.jax.org/report.html. CONTACT:
      mgi-help@informatics.jax.org

PMID- 10089203
TI  - TargetFinder: searching annotated sequence databases for target genes of
      transcription factors.
AB  - TargetFinder is a new software tool to search a database of annotated sequences
      for transcription factor binding sites located in context with other important
      transcription regulatory signals and regions, like the TATA element, the
      promoter, and so on, thereby greatly reducing the background usually associated
      with this kind of search. AVAILABILITY: The TargetFinder Web service is available
      at http://hercules.tigem.it/TargetFinder.html CONTACT: giovanni.lavorgna@hsr.it

PMID- 10089204
TI  - DnaSP version 3: an integrated program for molecular population genetics and
      molecular evolution analysis.
AB  - DnaSP is a Windows integrated software package for the analysis of the DNA
      polymorphism from nucleotide sequence data. DnaSP version 3 incorporates several
      methods for estimating the amount and pattern of DNA polymorphism and divergence,
      and for conducting neutrality tests. AVAILABILITY: For academic uses, DnaSP is
      available free of charge from: http://www.bio.ub.es/julio/DnaSP.html CONTACT:
      julio@porthos.bio.ub.es

PMID- 10089205
TI  - PredAcc: prediction of solvent accessibility.
AB  - PredAcc is a tool for predicting the solvent accessibility of protein residues
      from the sequence at different relative accessibility levels (0-55%). The
      prediction rate varies between 70. 7% (for 25% relative accessibility) and 85.7%
      (for 0% relative accessibility). Amino acids are predicted in four categories:
      almost certainly hidden and almost certainly exposed with a given a posteriori
      prediction error, probably hidden and probably exposed otherwise. AVAILABILITY:
      http://condor.urbb.jussieu.fr/PredAccCfg.html CONTACT: tuffery@urbb.jussieu.fr

PMID- 10089206
TI  - Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates,
      and bacteria.
AB  - On the basis of function and sequence similarities, the vertebrate
      fucosyltransferases can be classified into three groups: alpha-2-, alpha-3-, and
      alpha-6-fucosyltransferases. Thirty new putative fucosyltransferase genes from
      invertebrates and bacteria and six conserved peptide motifs have been identified
      in DNA and protein databanks. Two of these motifs are specific of alpha-3
      fucosyltransferases, one is specific of alpha-2-fucosyltransferases, another is
      specific of alpha-6-fucosyltransferases, and two are shared by both alpha-2- and
      alpha-6-fucosyltranserases. Based on these data, literature data, and the
      phylogenetic analysis of the conserved peptide motifs, a model for the evolution
      offucosyltransferase genes by successive duplications, followed by divergent
      evolution is proposed, with either two different ancestors, one for the alpha-2/6
      fucosyltransferases and one for the alpha-3-fucosyltransferases or a single
      common ancestor for the two families. The expected properties of such an
      hypothetical ancestor suggest that the plant or insect alpha-3
      fucosyltransferases using chitobiose as acceptor might be the present forms of
      this ancestor, since fucosyltransferases using chitobiose as acceptor are
      expected to be of earlier appearance in evolution than enzymes using N 
      acetyllactosamine. However, an example of convergent evolution of
      fucosyltransferase genes is suggested for the appearance of the Leaepitopes found
      in plants and primates.

PMID- 10089207
TI  - Characterization of mannooligosaccharide caps in mycobacterial lipoarabinomannan
      by capillary electrophoresis/electrospray mass spectrometry.
AB  - A new analytical approach based on capillary electrophoresis-electrospray mass
      spectrometry (CE/ESI-MS) has provided new insight into the characterization of
      mannooligosaccharide caps from lipoarabinomannans (LAMs), which are key molecules
      in the immunopathogenesis of tuberculosis. This analytical approach requires
      oligosaccharide labeling with the fluorophore 1-aminopyrene-3,6,8-trisulfonate
      (APTS) by reductive amination at the reducing termini. Optimization of the
      separation and ionization conditions, such as the choice of capillary
      electrophoresis (CE) electrolyte buffers, is presented and discussed. Anionic
      separation of the mono and oligosaccharide APTS derivatives was finally achieved
      with aqueous triethylammonium formate buffer. It was found that in contrast to
      the triethylammonium phosphate buffer, the triethylammonium formate buffer was
      appropriate for CE/ESI-MS coupling analysis of APTS-carbohydrate derivatives. In
      this case, negative ESI-mass spectra of APTS-carbohydrate adducts showed mainly
      (M-2H)2-pseudomolecular ions and some sequence fragment ions allowing their non
      ambiguous structural characterization at the picomolar level. This analytical
      approach was successfully applied to more complex mixtures of carbohydrates
      released by mild acid hydrolysis of the lipoarabinomannans from Mycobacterium
      bovis BCG. The APTS-mannooligosaccharide cap adducts were separated by CE and
      their structural characterization achieved by CE/ESI-MS analyses.
      Mannooligosaccharide caps were routinely analyzed by capillary electrophoresis
      laser induced fluorescence (CE-LIF) from 50 fmol of lipoarabinomannans with
      mannosyl capping (ManLAMs) but sensitivity was about 50 times lower using ESI-MS
      detection.

PMID- 10089208
TI  - A statistical analysis of N- and O-glycan linkage conformations from
      crystallographic data.
AB  - We have generated a database of 639 glycosidic linkage structures by an
      exhaustive survey of the available crystallographic data for isolated
      oligosaccharides, glycoproteins, and glycan-binding proteins. For isolated
      oligosaccharides there is relatively little crystallographic data available. A
      much larger number of glycoprotein and glycan-binding protein structures have now
      been solved in which two or more linked monosaccharides can be resolved. In the
      majority of these cases, only a few residues can be seen. Using the 639
      glycosidic linkage structures, we have identified one or more distinct conformers
      for all the linkages. The O5-C1-O-C(x)' torsion angles for all these distinct
      conformers appear to be determined chiefly by the exo-anomeric effect. The
      Manalpha1-6Man linkage appears to be less restrained than the others, showing a
      wide degree of dispersion outside the ranges of the defined conformers. The
      identification of distinct conformers for glyco-sidic linkages allows "average"
      glycan structures to be modeled and also allows the easy identification of
      distorted glycosidic linkages. Such an analysis shows that the interactions
      between IgG Fc and its own N-linked glycan result in severe distortion of the
      terminal Galbeta1-4GlcNAc linkage only, indicating the strong interactions that
      must be present between the Gal residue and the protein surface. The
      applicability of this crystallographic based analysis to glycan structures in
      solution is discussed. This database of linkagestructures should be a very useful
      reference tool in three-dimensional structure determinations.

PMID- 10089209
TI  - Enzymatic synthesis of natural and 13C enriched linear poly-N-acetyllactosamines
      as ligands for galectin-1.
AB  - As part of a study of protein-carbohydrate interactions, linear N-acetyl
      polyllactosamines [Galbeta1,4GlcNAcbeta1,3]nwere synthesized at the 10-100
      micromol scale using enzymatic methods. The methods described also provided
      specifically [1-13C]-galactose-labeled tetra- and hexasaccharides ([1-13C]
      Galbeta1,4GlcNAcbeta1,3Galbeta1,4Glc and Galbeta1, 4GlcNAcbeta1,3[1
      13C]Galbeta1,4GlcNAcbeta1,3Galbeta 1,4Glc) suitable for NMR studies. Two series
      of oligosaccharides were produced, with either glucose or N-acetlyglucosamine at
      the reducing end. In both cases, large amounts of starting primer were available
      from human milk oligosaccharides (trisaccharide primer GlcNAcbeta1,3Galbeta1,
      4Glc) or via transglycosylation from N-acetyllactosamine. Partially purified and
      immobilized glycosyltransferases, such as bovine milk beta1,4
      galactosyltransferase and human serum beta1,3 N- acetylglucosaminyltransferase,
      were used for the synthesis. All the oligo-saccharide products were characterized
      by1H and13C NMR spectroscopy and MALDI-TOF mass spectrometry. The target
      molecules were then used to study their interactions with recombinant galectin-1,
      and initial1H NMR spectroscopic results are presented to illustrate this
      approach. These results indicate that, for oligomers containing up to eight
      sugars, the principal interaction of the binding site of galectin-1 is with the
      terminal N-acetyllactosamine residues.

PMID- 10089210
TI  - N-Glycosylation of a mouse IgG expressed in transgenic tobacco plants.
AB  - Since plants are emerging as an important system for the expression of
      recombinant glycoproteins, especially those intended for therapeutic purposes, it
      is important to scrutinize to what extent glycans harbored by mammalian
      glycoproteins produced in transgenic plants differ from their natural
      counterpart. We report here the first detailed analysis of the glycosylation of a
      functional mammalian glycoprotein expressed in a transgenic plant. The structures
      of the N-linked glycans attached to the heavy chains of the monoclonal antibody
      Guy's 13 produced in transgenic tobacco plants (plantibody Guy's 13) were
      identified and compared to those found in the corresponding IgG1 of murine
      origin. Both N-glycosylation sites located on the heavy chain of the plantibody
      Guy's 13 are N-glycosylated as in mouse. However, the number of Guy's 13
      glycoforms is higher in the plant than in the mammalian expression system.
      Despite the high structural diversity of the plantibody N-glycans, glycosylation
      appears to be sufficient for the production of a soluble and biologically active
      IgG in the plant system. In addition to high-mannose-type N-glycans, 60% of the
      oligosaccharides N-linked to the plantibody have beta(1, 2)-xylose and alpha(1,
      3)-fucose residues linked to the core Man3GlcNAc2. These plant-specific
      oligosaccharide structures are not a limitation to the use of plantibody Guy's 13
      for topical immunotherapy. However, their immunogenicity may raise concerns for
      systemic applications of plantibodies in human.

PMID- 10089211
TI  - Molecular behavior of mutant Lewis enzymes in vivo.
AB  - The expression of type-1 Lewis antigens on erythrocytes and in digestive organs
      is determined by a Lewis type alpha(1,3/1, 4)-fucosyltransferase (Lewis enzyme)
      encoded by the Fuc-TIII gene ( FUT3 gene; Lewis gene). We have classified the
      Lewis alleles in the Japanese population into four types, the wild-type allele (
      Le ) and three mutated alleles, i.e., le1, which has missense mutations T59G and
      G508A, le2, which has T59G and T1067A, and le3, which has only T59G. Here we
      carried out an extensive study on the biological properties of the three mutant
      Lewis enzymes, the le1, le2, and le3 enzymes, using native tissues and obtained
      the following results. (1) In in vivo and in vitro experiments, the le1 and le2
      enzymes were found to be susceptible to protease digestion probably because the
      one missense mutation in the catalytic domains, i.e., Gly170 to Ser in the le1
      enzyme and Ile356 to Lys in the le2 enzyme, makes the three-dimensional
      structures of the enzymesunstable, while the le3 and wild-type Lewis enzymes
      wereresistant to protease digestion. (2) The le1 and le2 enzymes cannot
      synthesize type 1 Lewis antigens on either glycolipids or mucins. The le3 enzyme
      cannot synthesize Lewis-active glycolipids, which result in the Lewis antigen
      negative phenotype of erythrocytes, while it can synthesize Lewis antigens on
      mucins in normal and cancerous colon tissues. The missense mutation, Leu20 to
      Arg, in the transmembrane domain reduces retention of the le3 enzyme in the Golgi
      membrane resulting in an apparent reduction of enzyme activity as revealed by the
      lack of Lewis antigen synthesis. (3) The Lewis gene dosage actually has effects
      in vivo on the amount of the Lewis enzyme, its activity, and finally the amounts
      of Lewis carbohydrate antigens. This is the first article that clearly
      demonstrates the gene dosage effects on the amount of the glycosyltransferase
      protein, its activity, and the amounts of carbohydrate products in vivo.

PMID- 10089212
TI  - The tat protein of HIV-1 induces galectin-3 expression.
AB  - Animal lectins play important roles in a variety of biological processes via
      their recognition of glycoconjugates. Galectin-3 is a beta-galactoside-binding
      lectin whose expression is associated with various pathological processes
      including human T lymphotropic virus (HTLV)-I-infection of human T cell lines and
      human immunodeficiency virus (HIV) infection of T-lymphoblastic Molt-3 cell line.
      In the case of HIV-infected cells, it has been suggested that the increase in
      galectin-3 expression could be related to the expression of the viral regulatory
      gene tat. These results prompt us to perform more extensive analyses of the
      relationship between galectin-3 and HIV-1 Tat expressions. In this study, we
      found that Tat protein expression induces an upregulation of galectin-3 in
      several human cell lines. In co-transfection experiments, the 5'-regulatory
      sequences of the galectin-3 gene were significantly upregulated by expression
      vectors encoding the Tat protein. Analysis performed with 5'-regulatory deleted
      sequences suggested that galectin-3 induction by Tat is dependent on activation
      of the Sp-1 binding transcription factor.

PMID- 10089213
TI  - CFTR expression does not influence glycosylation of an epitope-tagged MUC1 mucin
      in colon carcinoma cell lines.
AB  - The cause of the mucus clearance problems associated with cystic fibrosis remains
      poorly understood though it has been suggested that mucin hypersecretion,
      dehydration of mucins, and biochemical abnormalities in the glycosylation of
      mucins may be responsible. Since the biochemical and biophysical properties of a
      mucin are dependent on O-glycosylation, our aim was to evaluate the O
      glycosylation of a single mucin gene product in matched pairs of cells that
      differed with respect to CFTR expression. An epitope-tagged MUC1 mucin cDNA
      (MUC1F) was used to detect variation in mucin glycosylation in stably transfected
      colon carcinoma cell lines HT29 and Caco2. The glycosylation of MUC1F mucin was
      evaluated in matched pairs of Caco2 cell lines that either express wild-type CFTR
      or have spontaneously lost CFTR expression. The general glycosylation pattern of
      MUC1F was evaluated by determining its reactivity with a series of monoclonal
      antibodies against known blood group and tumor-associated carbohydrate antigens.
      Metabolic labeling experiments were used to estimate the gross levels of
      glycosylation and sulfation of MUC1F mucin in these matched pairs of cell lines.
      Expression of CFTR in this experimental system did not affect the gross levels of
      glycosylation or sulfation of the MUC1F mucin nor the types of carbohydrates
      structures attached to the MUC1F protein.

PMID- 10089214
TI  - Differential expression of alpha2-6 sialylated polylactosamine structures by
      human B and T cells.
AB  - We found that human peripheral B and T cells differed in the surface expression
      of alpha2-6 sialylated type 2 chain glycans. In contrast to B cells, T cells
      expressed only sialoglycans with repeated N-acetyllactosamine (Galss1-4GlcNAc)
      disaccharides. This finding was based on the specificity of the monoclonal
      antibodies HB6, HB9 (CD24), HD66 (CDw76), FB21, and CRIS4 (CDw76) with the alpha2
      6 sialylated model gangliosides IV6NeuAcnLc4Cer (2-6 SPG), VI6NeuAcnLc6Cer (2-6
      SnHC), VIII6NeuAcnLc8Cer (2-6 SnOC), and X6NeuAcnLc10Cer (2-6 SnDC). We found
      that, in addition to their common requirement of an alpha2-6 bound terminal
      sialic acid for binding, the antibodies displayed preferences for the length of
      the carbohydrate backbones. Some of them bound mainly to 2-6 SPG with one N
      acetyllactosamine (LacNAc) unit (HB9, HD66); others preferentially to 2-6 SnHC
      and 2-6 SnOC, with two and three LacNAc units, respectively (HB6 and FB21); and
      one of them exclusively to very polar alpha2-6 sialylated type 2 chain antigens
      (CRIS4) such as to 2-6 SnOC and even more polar gangliosides with three and more
      LacNAc units. These specificities could be correlated with the cellular binding
      of the antibodies as follows: whereas all antibodies bound to human CD 19
      positive peripheral B cells, their reactivity with CD3 positive T cells was
      either nearly lacking (HD66, HB9), intermediate (about 65%: HB6, FB21) or
      strongly positive (CRIS4, 95%). Thus, the binding of the antibodies to 2-6
      sialylated glycans with multiple lactosamine units appeared to determine their
      binding to T-cells.

PMID- 10089215
TI  - Complete glycan structure of the S-layer glycoprotein of Aneurinibacillus
      thermoaerophilus GS4-97.
AB  - Isolate GS4-97 was purified from an extraction juice sample of an Austrian beet
      sugar factory and affiliated to the newly described species Aneurinibacillus
      thermoaerophilus. It is closely related to the type strain of this species,
      A.thermoaerophilus L420-91(T), and possesses a square surface layer (S-layer)
      array composed of identical glycoprotein monomers as its outermost cell envelope
      component. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the
      purified S-layer showed an apparent molecular mass of approximately 109,000.
      After thorough proteolytic degradation of this material by pronase E and
      purification of the reaction mixture by gel permeation, chromatofocusing, and
      reversed-phase chromatography, a homogeneous glycopeptide fraction was obtained
      which was subjected to one- and two-dimensional nuclear magnetic resonance
      spectroscopy. The combined chemical and spectroscopic evidence, together with N
      terminal sequencing, suggest the following structure of the O-glycosidically
      linked S-layer glycan chain of the glycopeptide: This is the first description of
      a beta-d-GalNAc-Thr linkage in glycoproteins.

PMID- 10089216
TI  - Differences between the trypanosomal and human GlcNAc-PI de-N-acetylases of
      glycosylphosphatidylinositol membrane anchor biosynthesis.
AB  - De-N-acetylation of N-acetylglucosaminyl-phosphatidylino-sitol (GlcNAc-PI) is the
      second step of glycosylphosphatidylino-sitol (GPI) membrane anchor biosynthesis
      in eukaryotes. This step is a prerequisite for the subsequent processing of
      glucosaminyl-phosphatidylinositol (GlcN-PI) that leads to mature GPI membrane
      anchor precursors, which are transferred to certain proteins in the endoplasmic
      reticulum. In this article, we used a direct de-N-acetylase assay, based on the
      release of [14C]acetate from synthetic GlcN[14C]Ac-PI and analogues thereof, and
      an indirect assay, based on the mannosylation of GlcNAc-PI analogues, to study
      the substrate specificities of the GlcNAc-PI de-N-acetylase activities of African
      trypanosomes and human (HeLa) cells. The HeLa enzyme was found to be more
      fastidious than the trypanosomal enzyme such that, unlike the trypanosomal
      enzyme, it was unable to act on a GlcNAc-PI analogue containing 2-O-octyl-d- myo 
      inositol or on the GlcNAc-PI diastereoisomer containing l- myo -inositol (GlcNAc
      P(l)I). These results suggest thatselective inhibition of the trypanosomal de-N
      acetylase may be possible and that this enzyme should be considered as a possible
      therapeutic target. The lack of strict stereospecificity of the trypanosomal de-N
      acetylase for the d- myo -inositol component was also seen for the trypanosomal
      GPI alpha-manno-syltransferases when GlcNAc-P(l)I was added to the trypanosome
      cell-free system, but not when GlcN-P(l)I was used. In an attempt to rationalize
      these data, we modeled the structure and dynamics of d-GlcNAcalpha1-6d- myo 
      inositol-1-HPO4-( sn )-3-glycerol and its diastereoisomer d-GlcNAcalpha1-6l- myo 
      inositol-1-HPO4-( sn )-3-glycerol. These studies indicate that the latter
      compound visits two energy minima, one of which resembles the low-energy
      conformer of former compound. Thus, it is conceivable that the trypanosomal de-N
      acetylase acts on GlcNAc-P(l)I when it occupies a GlcNAc-PI-likeconformation and
      that GlcN-P(l)I emerging from the de-N-acetylase may be channeled to the alpha
      mannosyltransferases in this conformation.

PMID- 10089217
TI  - Calcidiol and PTH levels in women attending an osteoporosis program.
AB  - We performed a retrospective study of 237 patients attending a specialty
      osteoporosis practice. Secondary causes for reduced bone mineral density (BMD)
      were evaluated in 196 postmenopausal women and 41 premenopausal women; mean age
      was 56 +/- 13.8 years (mean +/- SD). BMD was measured by dual-energy X-ray
      absorptiometry (DXA) (QDR 1000W/2000 Hologic). Levels of intact parathyroid
      hormone (iPTH), calcidiol [25(OH)D], thyroid-stimulating hormone, and 24-hour
      urinary calcium were measured, and serum and urine protein (SPEP and UPEP)
      electrophoresis were performed. Overall, 16% of our patients had 25(OH)D levels
      <15 ng/ml, the lowest acceptable vitamin D level without a concomitant rise in
      iPTH levels. Among the osteoporotic patients (T score <-2.5 SD), 17% had 25(OH)D
      levels <15 ng/ml and 7% <10 ng/ml. Among the osteopenic patients (-2.5 < T < -1.0
      SD), 11% had 25(OH)D levels <15 ng/ml. Seventeen percent of patients with Z score
      </=-1.0 SD (low range normal value) had 25(OH)D levels <15 ng/ml. Low 25(OH)D
      levels were inversely related to high iPTH values (r = 0.30, P < 0.0001).
      Hypercalciuria was present in 15% of our patients, elevations of PTH levels (>65
      pg/ml, upper normal limit of assay) were present in 11.5%, and hyperthyroidism in
      4%. A 25(OH)D level of <25 ng/ml in women (n = 86) with no known secondary causes
      of low BMD was associated with an iPTH level above 49 pg/ml. The measurement of
      25(OH)D levels is recommended in the evaluation of secondary causes for reduced
      BMD. Supplementation with vitamin D appears needed to keep 25(OH)D above 25
      ng/ml, the level required to prevent increments in iPTH levels.

PMID- 10089218
TI  - Influence of skeletal site of origin and donor age on osteoblastic cell growth
      and differentiation.
AB  - Bone loss with aging may be due, at least in part, to inadequate bone formation.
      Moreover, the process of bone aging is known to follow a different pattern
      throughout the skeleton. In this study, we examined the cell proliferation rate
      (area under the cell growth curve, AUC) and the secretion of C-terminal type I
      procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) in primary
      cultures of osteoblastic cells from human trabecular bone. Osteoblastic cells
      were obtained for 168 donors (100 women and 68 men). Ninety-eight bone samples
      were obtained from subjects undergoing knee arthroplastia, 52 aged 50-70 years
      (64 +/- 5) and 46 over age 70 (73 +/- 2). Another 70 bone samples were obtained
      from subjects undergoing hip arthroplastia; 51 were 50-70 years old (64 +/- 4)
      and 19 were over 70 (75 +/- 5). Osteoblastic cells from the older donors had a
      lower proliferation rate and OC secretion than those from younger subjects.
      However, ALP secretion was higher in the former subjects, whereas PICP secretion
      was unchanged. Osteoblastic cells from hip had a lower proliferation rate than
      those from knee. PICP secretion was also lower and ALP secretion was higher in
      the former cells. In age-matched cell cultures, osteoblastic cells from the knee
      had higher proliferation rate and PICP secretion than osteoblastic cells from the
      hip. However, ALP secretion was lower in knee osteoblastic cells than those from
      hip only in the younger group. With aging, ALP secretion was found to increase in
      knee osteoblactic cells, whereas OC secretion decreased in osteoblastic cell
      cultures from the hip. Our findings suggest that bone loss with aging may be
      accounted for, at least in part, by a decreased osteoblastic cell proliferation
      and an increased osteoblastic maturation. In addition, our data indicate that
      these changes with aging do not occur similarly at different skeletal sites.

PMID- 10089219
TI  - Transient dissociation of bone metabolism induced by high performance exercise: a
      study in elite marathon runners.
AB  - Bone metabolism parameters were studied in 18 elite marathon runners (11 men and
      7 women) who participated in the Marathon World Cup held at San Sebastian, Spain
      in 1993. Measurements were made before the race, immediately after the race, and
      24 hours after the race. The most interesting finding was increased alkaline
      phosphatase (P < 0. 0001) and decreased tartrate-resistant acid phosphatase (P =
      0.0035), which suggests that exercise produced uncoupling of the bone cell
      metabolism. Serum calcium corrected for proteins did not increase with exercise
      and at the end of the race there was a negative correlation between cortisol,
      which was significantly higher (P < 0. 0001), and corrected serum calcium (r =
      0.53, P = 0.026) that was not present at baseline. Running time showed a
      significant negative correlation with baseline serum cortisol (r = -0.67, P =
      0.0015) and a significant positive correlation with body mass index (r = 0.53, P
      = 0.0207). The increase in alkaline phosphatase persisted 24 hours after the
      race, which suggests that exercise produced an intense and sustained effect on
      osteogenic capacity.

PMID- 10089220
TI  - Maximum grip strength is not related to bone mineral density of the proximal
      femur in older adults.
AB  - In the past decade there have been numerous publications reporting a significant
      and direct relationship between handgrip strength and bone mineral density (BMD)
      of the proximal femur in older adults. The present report challenges the
      appropriateness of the methods, and thus the conclusions used in these studies.
      Specifically, these studies failed to control for the concomitant influence of
      body weight on both BMD and muscle strength. In the present study, maximum
      handgrip strength was measured using a conventional hand-held hydraulic
      dynamometer. Bone mineral density of the proximal femur was measured using dual
      energy X-ray absorptiometry (DXA). Using allometric scaling, the influence of
      body weight on the value of maximum handgrip strength was removed for the data of
      the women. A small, but significant relationship between BMD of the proximal
      femur and maximum handgrip strength was found that accounted for about 6% of the
      total variation. The relationship between BMD of the proximal femur and unscaled
      maximum handgrip strength was not significant for the men. The findings diminish
      the confidence in a protective effect of skeletal muscle on some nonadjacent
      skeletal structures and suggest that these relationships may benefit from being
      revisited. The results highlight the utility of allometric scaling in analyses in
      which the relationship between a physiological variable and a body dimension
      variable can be nonlinearly and simultaneously influenced by other body dimension
      variables that are not considered in the analysis and therefore are statistically
      uncontrolled.

PMID- 10089221
TI  - Bone density, vitamin D status, and disordered bone remodeling in end-stage
      chronic liver disease.
AB  - Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease
      (CLD). The aim of this study was to determine the relative contribution of
      increased resorption and decreased formation to hepatic osteodystrophy by
      measuring biochemical markers. Twenty-seven patients with advanced CLD (14
      female, 13 male) were enrolled. Bone mineral density (BMD), measured at the
      lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry
      (DXA); bone turnover was assessed using biochemical markers of bone formation and
      resorption. Based on WHO criteria, osteoporosis and osteopenia were present in
      41% and 18% of patients, respectively. All three markers of bone resorption (free
      deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly
      in patients with CLD. There was a less marked change in the markers of bone
      formation (osteocalcin, procollagen type 1 peptide, and bone alkaline
      phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the
      patients. Only two (7%) patients had biochemical changes consistent with
      osteomalacia. The results suggest that increased bone resorption is the
      predominant cause of hepatic osteodystrophy and therapeutic strategies should be
      designed to suppress bone resorption, especially in preparation for liver
      transplantation. Bone biomarkers may be useful alternatives to bone biopsy in
      evaluating hepatic osteodystrophy.

PMID- 10089222
TI  - High bilirubin levels interfere with serum tartrate-resistant acid phosphatase
      determination: relevance as a marker of bone resorption in jaundiced patients.
AB  - Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a
      biochemical marker of bone resorption. Recently, a lack of specificity of
      collagen-related markers for assessing bone turnover has been observed in
      patients with chronic liver disease. Thus, it could be of great interest to
      determine serum TRAcP activity in such patients. However, nonspecificity of the
      analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are
      analyzed. Therefore, we have studied the interference caused by bilirubin in the
      measurement of serum TRAcP activity using the Hillmann method. The interference
      was assessed in two pools of serum containing different bilirubin concentrations
      but with similar total AcP levels. Mixing proportional parts of the two pools, 10
      samples were also obtained. Serum activities of total AcP and TRAcP, and the
      concentration of bilirubin were measured in the 10 samples. Both the actual and
      the expected values obtained by theoretical calculations were compared. Serum
      bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the
      determination of serum TRAcP activity, whereas values of bilirubin higher than 10
      mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not
      interfere with the total AcP determination. This study clearly shows the
      interference of bilirubin in the determination of serum TRAcP. This finding
      should be considered when bone metabolism disorders are evaluated in jaundiced
      patients.

PMID- 10089223
TI  - Hormonal regulation of the osteoblastic phenotype expression in neonatal murine
      calvarial cells.
AB  - Osteoblastic cell cultures from fetal rat calvariae have provided a popular model
      for studying the effects of dexamethasone (DEX) and 1, 25 dihydroxyvitamin D3
      [1,25(OH)2D3] on gene expression but data from murine calvarial cells are scarce.
      Species-specific responses of rat and mouse osteoblastic cells to these hormones
      have been reported previously. In the present study, we investigated the effects
      of DEX and 1,25(OH)2D3 on expression of the osteoblastic phenotype by mouse
      calvarial cells. These murine osteoblast-like (MOB) cells expressed alkaline
      phosphatase (ALP) activity and osteocalcin and formed calcified nodules. Unlike
      the rat calvarial cells, ALP activities and nodule formation in MOB were
      inhibited by DEX. 1,25(OH)2D3 enhanced and DEX lowered the amount of osteocalcin
      synthesized by MOB. 1,25(OH)2D3 did not affect the number of nodules, but
      increased their sizes. Treating the cells for 2 days with only DEX at the
      beginning of the culture enhanced the effect of 1, 25(OH)2D3 on ALP. We found
      that in murine calvarial cells, DEX inhibits and 1,25(OH)2D3 enhances ALP
      activity, osteocalcin synthesis, and calcified nodule formation. This is in
      contrast to previous reports of rat calvarial cells where DEX is a positive and
      1,25(OH)2D3 can be a negative regulator of the osteoblastic phenotype. These
      results suggest that profound species-specific differences exist between mice and
      rats in the regulation of the osteoblastic phenotype.

PMID- 10089224
TI  - The role of chondrocytes in intramembranous and endochondral ossification during
      distraction osteogenesis in the rabbit.
AB  - We have used a rabbit leg-lengthening model for detailed studies of the histology
      of distraction osteogenesis. Some unusual features of the endochondral
      ossification that occurs during the rapid transition of cartilage to bone in the
      regenerate were observed. Histological staining techniques together with
      immunohistochemistry and nonradioactive in situ mRNA hybridization for cartilage
      and bone-related molecules have been used to document the presence of an
      overlapping cartilage-bone phenotype in cells of the cartilage-bone transitional
      region. In those particular areas, some chondrocytes appeared to be directly
      transformed into newly formed bone trabeculae which are surrounded by bone
      matrix. Acid phosphatases were found within the cartilage matrix in some of the
      cartilage/bone transitional regions and type I collagen mRNA and type II collagen
      protein were found together in some of the marginal hypertrophic chondrocytes.
      This study indicates an unusual role of chondrocytes in the process of
      ossification at a distraction rate of 1.3 mm/day in the rabbit. Further direct
      evidence is required to prove the hypothesis that the hypertrophic chondrocytes
      may transdifferentiate into bone cells in this model.

PMID- 10089225
TI  - Histomorphometric evaluation of the effects of ovariectomy on bone turnover in
      rat caudal vertebrae.
AB  - The purpose of this study was to learn whether caudal vertebrae can be used to
      evaluate the effects of ovariectomy (OVX) in rats. Seven-month-old female Wistar
      rats were divided into two groups: the OVX group and the untreated control group.
      All rats were killed at 8 weeks and their 4th lumbar (L4), 1st caudal (C1), 3rd
      caudal (C3), and 5th caudal (C5) vertebrae were processed undecalcified and
      sectioned with Villanueva bone stain for quantitative bone histomorphometry. Both
      length of vertebral bodies and the cancellous tissue area in C1 were similar in
      size to L4 but significantly bigger than C3 and C5. Within the groups, cancellous
      bone volume (BV/TV) and trabecular thickness in both groups gradually increased
      in caudal vertebrae in relation to the distal direction. Between the groups, OVX
      rats exhibited a significantly lower BV/TV relative to control rats at L4 and C1,
      however, no significant difference were seen at C3 and C5. Bone formation-related
      parameters such as osteoid and mineralizing surface, and eroded surface were
      higher in the OVX group than in the control group in caudal as well as in lumbar
      vertebrae. By quantitative analysis of bone marrow composition, yellow marrow
      volume in C3 and C5 was significantly higher than that in L4 and C1, in both
      groups. Our results suggest that C1 is similar to L4 in size, bone turnover, and
      bone marrow composition. However, further experiments are needed to evaluate the
      possibility that C1 vertebra could be used as an alternative site for
      histomorphometric evaluation of bone changes in OVX rats.

PMID- 10089226
TI  - The effect of estrogen deficiency on calcium balance in mature rats.
AB  - The role of estrogen in the regulation of calcium balance is still poorly
      understood. A calcium balance study was performed to examine the effects of
      estrogen status in relation to fecal calcium loss as a component of bone loss
      after oophorectomy (OOX) in the mature rat. The components of the classic calcium
      balance were compared with calcium balance estimates obtained from whole body
      bone density. Six month or older Sprague Dawley rats were allocated to either a
      sham-operated or OOX group and fed a 0.1% calcium diet. The bone mineral density
      (BMD) and bone mineral content (BMC) were measured at baseline, 6 weeks, and 9
      weeks. A calcium balance was done for 6 days before and 6 weeks post OOX. The
      fall in BMD from baseline to 9 weeks in the OOX group was significantly greater
      than in the sham-operated group. The calcium balance was more negative at
      baseline than at 6 weeks in both groups of animals because they had not adapted
      to the low calcium diet. However, the increase in calcium balance was
      significantly less in the OOX animals than in the sham-operated animals. The
      greater the rise in calcium balance from the baseline to the 6 weeks balance the
      less the fall in the calcium content of the whole body (Spearman correlation: r =
      0.604 P = 0.008). The fall in fecal calcium, but not urine calcium or calcium
      consumed, was negatively correlated with the change in whole body BMC (Spearman
      correlation: fecal calcium r = -0.763 P = 0.001). Thus, the primary effect of
      estrogen deficiency on calcium balance in the mature rat appears to be calcium
      flux in the bowel, rather than renal calcium handling.

PMID- 10089227
TI  - Metastable equilibrium solubility behavior of bone mineral.
AB  - Previous studies have shown that carbonated apatites with a range of carbonate
      contents and crystallinities exhibit the phenomenon of metastable equilibrium
      solubility (MES) distributions. The purpose of the present study was to
      investigate the solubility behavior of bone mineral using the concepts of MES and
      MES distributions and, together with crystallinity and chemical composition data,
      examine the similarity of bone mineral to carbonated apatite (CAP). Bone samples
      were harvested from 1-, 5-, and 8-month-old rats. The organic components of the
      bone samples were removed by hydrazine deproteination. Carbonated apatite was
      synthesized by the hydrolysis of dicalcium phosphate dihydrate (DCPD) in a NaHCO3
      containing media at 50 degrees C. The MES distributions of bone mineral and CAP
      were determined by equilibrating predetermined amounts of CAP or bone mineral in
      a series of 0.1 M acetate buffers containing calculated levels of calcium and
      phosphate and maintained at essentially constant pHs of 5.0, 5.3, 5.7, and 6.5.
      From the compositions of the equilibrating buffer solutions, ion activity
      products based upon the stoichiometries of octacalcium phosphate, hydroxyapatite,
      and carbonated apatite were calculated in an attempt to determine the function
      governing the dissolution of CAP and bone mineral. The results of this study
      demonstrated that the MES distribution phenomenon appeared to hold for bone
      mineral and that the changes in crystallinity of bone mineral with age correlated
      well with changes in the MES values. A CAP sample was prepared that was found to
      be an excellent synthetic prototype closely mimicking the physicochemical
      behavior of bone mineral from an 8-month-old rat. Another finding of this study
      was that the ion activity product function based upon the hydroxyapatite
      stoichiometry well described the MES results obtained with both CAP and bone
      mineral. The interpretation that a surface complex with hydroxyapatite
      stoichiometry governs the solubility behavior of bone mineral is, therefore,
      consistent with the experimental data. Other calcium phosphate stoichiometries
      for the surface complex showed systematic variations in the MES profiles when the
      pH of the equilibrating solution was varied.

PMID- 10089228
TI  - Improved bone biomechanical properties in rats after oral xylitol administration.
AB  - The effects of 5, 10, and 20% dietary xylitol supplementations on the
      biomechanical properties, histological architecture, and the contents of
      collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied.
      Tibiae were used for the three-point bending test, and femurs were used for the
      torsion and loading test of the femoral neck. The 10 and 20% oral xylitol
      administrations caused a significant increase of tibial stress, femoral shear
      stress, and stress of the femoral neck as compared with the controls. Parallel,
      but not significant, effects were also seen in the 5% xylitol supplementation
      group. No significant differences in strain or Young's modulus of the tibiae were
      detected between the groups. An increased shear modulus of elasticity in femurs
      was detected in the 20% supplementation group as compared with the controls. The
      histomorphometrical data for the secondary spongiosa of the proximal tibia
      revealed that trabecular bone volume was significantly greater in all dietary
      xylitol supplementation groups as compared with the controls. The bone volume
      increased along with increasing xylitol content. No significant differences
      between the groups were detected concerning the amount of collagen per dry weight
      of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in
      collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent
      selective changes in these structures of bone collagen. In conclusion, dietary
      xylitol supplementation in rats improves the biomechanical properties of bone and
      increases the trabecular bone volume dose dependently.

PMID- 10089229
TI  - The effect of fluoride treatment on bone mineral in rabbits.
AB  - Fluoride therapy has been used clinically for many years, but its use remains
      controversial and many basic questions remain unanswered. Accordingly, this study
      returns to an animal model to study the effects of high doses of fluoride on bone
      mineral in rabbits. Twelve rabbits, aged 3(1/2) months at the start of the study,
      received drinking water fluoridated at 100 ppm while their 12 control
      counterparts drank distilled water. All rabbits were sacrificed after 6 months.
      Fluoride was readily incorporated into femoral cortical bone (7473 +/- 966 ppm F
      versus 1228 +/- 57 ppm in controls; P < 0.00005). Fluoride therapy led to
      increased mineralization, as measured by density fractionation (P < 0.0005 for
      the distributions). The bone mineral itself was altered, with a significant
      increase in the width of crystals (66.2 +/- 2.0 A versus 61.2 +/- 0.9 A; P <
      0.01). The microhardness of both cortical and cancellous bone in the femoral head
      of fluoride-treated rabbits was greater than that in the controls (P < 0.05). The
      phosphate, calcium, and carbonate contents in the bone was the same in both
      groups. Finally, fluoride administration did not affect the architecture or
      connectivity of cancellous bone in the femoral head. Previously published data
      [1] indicated that the mechanical properties of bone were adversely affected;
      this suggests that the effect of high doses of fluoride on the strength and
      stiffness of bone may be mediated by its effect on bone mineral.

PMID- 10089230
TI  - Urinary 3H-tetracycline and pyridinium crosslinks differ in their response to
      calcium restriction in mature and aged rats.
AB  - The aim of this study was to evaluate bone resorption (BR) in rats by two
      methods: chronic 3H-tetracycline labeling (3HTC) and pyridinium crosslink
      excretion (PYDX), and compare the sensitivity of these markers in two age groups.
      Female Sprague-Dawley rats at 12-29 weeks of age ("mature", n = 12) and at 40-57
      weeks of age ("aged", n = 22) were examined. Skeletal incorporation of 3HTC in
      aged rats was 43 +/- 8% of that in mature animals (P < 0.01), indicating an age
      related decrease in bone turnover. BR was modulated over 9 weeks by calcium
      restriction (CR), measured by urinary excretion of both 3HTC and PYDX, and
      compared with age-matched, calcium-adequate controls. At baseline, urinary
      excretion of 3HTC was not significantly different between age groups, whereas
      urinary PYDX was 14-20% higher in mature compared with aged rats (P < 0.01). CR
      produced a 32-39% peak increase in BR (P < 0.01) compared with controls that did
      not differ significantly between marker or age group. Urinary 3HTC was elevated
      at weeks 1-3 (P < 0. 01) and reached maximal values at week 2 (32 +/- 17%).
      Urinary PYDX, however, was not elevated until week 2, reached maximal levels at
      week 3 (39 +/- 15%), and remained elevated until week 6 (P < 0.01). These data
      indicate that although both markers are elevated by CR, marker response differs
      with age, and variability exists for acute and chronic responses.

PMID- 10089231
TI  - Effect of anterior cruciate ligament injury of the knee on bone mineral density
      of the spine and affected lower extremity: a prospective one-year follow-Up
      study.
AB  - The objective of this 1-year prospective follow-up study was to assess, with dual
      energy X-ray absorptiometry (DXA), the effect of an anterior cruciate ligament
      (ACL) injury of the knee on areal bone mineral density (BMD) of the injured
      extremity and lumbar spine in two separate patient groups: 21 surgically treated
      patients (group A) and 12 conservatively treated patients (group B). Clinical and
      functional status of the patients and BMD of the spine (L2-L4), dominant distal
      radius, femoral neck, trochanter area of the femur, distal femur, patella,
      proximal tibia, and calcaneus of both lower extremities were determined at the
      time of the injury and after 4, 8, and 12 months. A surgically treated, complete
      ACL rupture (group A) resulted in considerable and statistically significant bone
      loss to the affected knee (distal femur 21%, patella 17%, proximal tibia 14%; P <
      0.001 in each), whereas the other sites were clearly less affected. Patients with
      a conservatively treated, complete or partial ACL injury (group B) had only a
      small but statistically significant bone loss at the patella (-3%; P = 0.005) and
      proximal tibia (-2%; P = 0.022) of the injured knee, and the other sites remained
      unchanged. The obvious differences between the groups A and B in the severity of
      the injury itself (complete or partial tear), its treatment (surgical or
      conservative), and subsequent rehabilitation (longer nonweight-bearing times in
      group A) explain these different BMD results, and the forthcoming years will show
      whether the considerable posttraumatic osteoporosis in the affected knee of group
      A patients will finally recover, and if so, to what extent.

PMID- 10089232
TI  - Regulatory function of Na-Ca exchange in the heart: milestones and outlook.

PMID- 10089233
TI  - Osmotic shrinkage activates nonselective cation (NSC) channels in various cell
      types.
AB  - Osmotic cell shrinkage activates a nonselective cation (NSC) channel in M-1 mouse
      cortical collecting duct cells (Volk, Fromter & Korbmacher, 1995, Proc. Natl.
      Acad. Sci. USA 92: 8478-8482). To see whether shrinkage-activated NSC channels
      are an ubiquitous phenomenon, we tested the effect of hypertonic extracellular
      solution on whole-cell currents of HT29 human colon carcinoma cells, BSC-1 renal
      epithelial cells, A10 vascular smooth muscle cells, and Neuro-2a neuroblastoma
      cells. Addition of 100 mm sucrose to an isotonic NaCl bath solution induced cell
      shrinkage of HT29 cells as evidenced by a decrease in cell diameter from 18 +/- 1
      microm to 12 +/- 1 microm (n = 13). Upon cell shrinkage whole-cell currents of
      HT29 cells increased within 8 +/- 1 min by about 30-fold (n = 13). Cell shrinkage
      and current activation were reversible upon return to isotonic solution.
      Replacement of bath Na+ by K+ or Li+ had almost no effect on the stimulated
      inward current. In contrast, replacement by N-methyl-d-glucamine (NMDG)
      completely abolished it and shifted the reversal potential from -4.5 +/- 0.7 mV
      to -57 +/- 4.1 mV (n = 10). Thus, the stimulated conductance is nonselective for
      alkali cations but highly selective for cations over anions with a cation-to
      anion permeability ratio of about 13. Flufenamic acid (100 microm) inhibited the
      stimulated current by 84 +/- 4.7% (n = 8). During the early phase of hypertonic
      stimulation single-channel transitions could be detected in whole-cell current
      recordings, and a gradual activation of 12 and more individual channels with a
      single-channel conductance of 17.6 +/- 0.9 pS (n = 4) could be resolved. In
      analogous experiments similar shrinkage-activated NSC channels were also observed
      in BSC-1 renal epithelial cells, A10 vascular smooth muscle cells, and Neuro-2a
      neuroblastoma cells. These findings indicate that shrinkage-activated NSC
      channels are an ubiquitous phenomenon and may play a role in volume regulation.

PMID- 10089234
TI  - A long-term blockade of L-type calcium currents upregulates the number of Ca2+
      channels in skeletal muscle.
AB  - The effects of a long-term blockade of L-type Ca2+ channels on membrane currents
      and on the number of dihydropyridine binding sites were investigated in skeletal
      muscle fibers. Ca2+ currents (ICa) and intramembrane charge movement were
      monitored using a voltage-clamp technique. The peak amplitude of ICa increased by
      more than 40% in fibers that were previously incubated for 24 hr in solutions
      containing the organic Ca2+ channel blocker nifedipine or in Ca2+-free
      conditions. A similar incubation period with Cd2+, an inorganic blocker, produced
      a moderate increase of 20% in peak ICa. The maximum mobilized charge (Qmax)
      increased by 50% in fibers preincubated in Ca2+-free solutions or in the presence
      of Cd2+. Microsomal preparations from frog skeletal muscle were isolated by
      differential centrifugation. Preincubation with Cd2+ prior to the isolation of
      the microsomal fraction doubled the number of 3H-PN200-110 binding sites and
      produced a similar increase in the values of the dissociation constant. The
      increase in the number of binding sites is consistent with the increase in the
      peak amplitude of ICa as well as with the increase in Qmax.

PMID- 10089235
TI  - Potassium uptake through the TOK1 K+ channel in the budding yeast.
AB  - The current through TOK1 (YKC1), the outward-rectifying K+ channel in
      Saccharomyces cerevisiae, was amplified by expressing TOK1 from a plasmid driven
      by a strong constitutive promoter. TOK1 so hyper-expressed could overcome the K+
      auxotrophy of a mutant missing the two K+ transporters, TRK1 and TRK2. This
      trk1Delta trk2Delta double mutant hyperexpressing the TOK1 transgene had a higher
      internal K+ content than one expressing the empty plasmid. We examined
      protoplasts of these TOK1-hyperexpressing cells under a patch clamp. Besides the
      expected K+ outward current activating at membrane potential (Vm) above the K+
      equilibrium potential (EK+), a small inward current was consistently observed
      when the Vm was slightly below EK+. The inward and the outward currents are
      similar in their activation rates, deactivation rates, ion specificities and Ba2+
      inhibition, indicating that they flow through the same channel. Thus, the yeast
      outwardly rectifying K+ channel can take up K+ into yeast cells, at least under
      certain conditions.

PMID- 10089236
TI  - Similarities in the effects of DIDS, DBDS and suramin on cardiac ryanodine
      receptor function.
AB  - The mechanisms involved in 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid
      (DIDS)- and 4,4'-dibenzamidostilbene-2, 2'-disulfonic acid (DBDS)- modification
      of sheep cardiac ryanodine receptor (RyR) channel function have been
      investigated. DIDS (50-500 microm) exerts at least three effects on single
      channel function. With Ca2+ as the permeant ion, DIDS increases both channel open
      probability (Po) and single channel conductance in a similar manner to the
      effects observed with suramin. Both effects occur immediately and are fully
      reversible. Similar effects were observed with DBDS (10 microm-2 mm), a compound
      with the 4,4'-NCS groups of DIDS replaced with NHCOC6H5. DIDS (500 microm) also
      caused irreversible modification to the fully open channel level in 74% of the
      channels. This effect was not observed with suramin or DBDS (10 microm-1 mm).
      Competition studies with DBDS and suramin coupled with the close similarities in
      the effects of DIDS, DBDS and suramin on gating and conduction suggest that these
      ligands may all bind to the same sites on RyR. The DIDS-induced irreversible
      modification to the fully open state may result from the binding of the
      isothiocyanate groups to positively charged amino acids at or near the suramin
      binding sites although it is possible that this modification is unrelated to its
      other effects on channel function.

PMID- 10089237
TI  - Electrogenic partial reactions of the SR-Ca-ATPase investigated by a fluorescence
      method.
AB  - A fluorescence method was adapted to investigate active ion transport in membrane
      preparations of the SR-Ca-ATPase. The styryl dye RH421 previously used to
      investigate the Na,K-ATPase was replaced by an analogue, 2BITC, to obtain
      optimized fluorescence changes upon substrate-induced partial reactions. Assuming
      changes of the local electric field to be the source of fluorescence changes that
      are produced by uptake/release or by movement of ions inside the protein, 2BITC
      allowed the determination of electrogenic partial reactions in the pump cycle. It
      was found that Ca2+ binding on the cytoplasmic and on the lumenal side of the
      pump is electrogenic while phosphorylation and conformational transition showed
      only minor electrogenicity. Ca2+ equilibrium titration experiments at pH 7.2 in
      the two major conformations of the protein indicated cooperative binding of two
      Ca2+ ions in state E1 with an apparent half-saturation concentration, KM of 600
      nm. In state P-E2 two KM values, 5 microm and 2.2 mM, were determined and are in
      fair agreement with published data. From Ca2+ titrations in buffers with various
      pH and from pH titrations in P-E2, it could be demonstrated that H+ binding is
      electrogenic and that Ca2+ and H+ compete for the same binding site(s).
      Tharpsigargin-induced inhibition of the Ca-ATPase led to a state with a specific
      fluorescence level comparable to that of state E1 with unoccupied ion sites,
      independent of the buffer composition.

PMID- 10089238
TI  - Determination of the individual electrical and transport properties of the
      plasmalemma and the tonoplast of the giant marine alga Ventricaria ventricosa by
      means of the integrated perfusion/charge-pulse technique: evidence for a
      multifolded tonoplast.
AB  - The charge-pulse relaxation spectrum of nonperfused and perfused (turgescent)
      cells of the giant marine alga Ventricaria ventricosa showed two main exponential
      decays with time constants of approximately 0.1 msec and 10 msec, respectively,
      when the cells were bathed in artificial sea water (pH 8). Variation of the
      external pH did not change the relaxation pattern (in contrast to other giant
      marine algae). Addition of nystatin (a membrane-impermeable and pore-forming
      antibiotic) to the vacuolar perfusion solution resulted in the disappearance of
      the slow exponential, whereas external nystatin decreased dramatically the time
      constant of the fast one. This indicated (by analogy to corresponding experiments
      with Valonia utricularis, J. Wang, I. Spiess, C. Ryser, U. Zimmermann, J.
      Membrane Biol. 157: 311-321, 1997) that the fast relaxation must be assigned to
      the RC-properties of the plasmalemma and the slow one to those of the tonoplast.
      Consistent with this, external variation of [K+]o or of [Cl-]o as well as
      external addition of K+- or Cl--channel/carrier inhibitors (TEA, Ba2+, DIDS)
      affected only the fast relaxation, but not the slow one. In contrast, addition of
      these inhibitors to the vacuolar perfusion solution had no measurable effect on
      the charge-pulse relaxation spectrum. The analysis of the data in terms of the
      "two membrane model" showed that K+- and (to a smaller extent) Cl--conducting
      elements dominated the plasmalemma conductance. The analysis of the charge-pulse
      relaxation spectra also yielded the following area-specific data for the
      capacitance and the conductance for the plasmalemma and tonoplast (by assuming
      that both membranes have a planar surface): (plasmalemma) Cp = 0.82 * 10(-2) F m
      2, Rp = 1.69 * 10(-2) Omega m2, Gp = 5.9 * 10(4) mS m-2, (tonoplast) Ct = 7. 1 *
      10(-2) F m-2, Rt = 14.9 * 10(-2) Omega m2 and Gt = 0.67 * 10(4) mS m-2. The
      electrical data for the tonoplast show that (in contrast to the literature) the
      area-specific membrane resistance of the tonoplast of these marine giant algal
      cells is apparently very high as reported already for V. utricularis. The
      exceptionally high value of the area-specific capacitance could be explained -
      among other interpretations - by assuming a 9-fold enlargement of the tonoplast
      surface. The hypothesis of a multifolded tonoplast was supported by transmission
      electronmicroscopy of cells fixed under maintenance of turgor pressure and of the
      electrical parameters of the membranes. This finding indicates that the tonoplast
      of this species exhibited a sponge-like appearance. Taking this result into
      account, it can be easily shown that the tonoplast exhibits a high-resistance
      (1.1 Omega m2). Vacuolar membrane potential measurements (performed in parallel
      with charge-pulse relaxation studies) showed that the potential difference across
      the plasmalemma was mainly controlled by the external K+-concentration which
      suggested that the resting membrane potential of the plasmalemma is largely a K+
      diffusion potential. After permeabilization of the tonoplast with nystatin the
      potential of the intact membrane barrier dropped from about slightly negative or
      positive (-5.1 to +18 mV, n = 13) to negative values (-15 up to -68 mV; n = 8).
      This indicated that the cytoplasm of V. ventricosa was apparently negatively
      charged relative to the external medium. Permeabilization of the plasmalemma by
      addition of external nystatin resulted generally in an increase in the potential
      to slightly more positive values (-0.8 to +4.3 mV; n = 5), indicating that the
      vacuole is positively charged relative to the cytoplasm. These findings
      apparently end the long-term debate about the electrical properties of V.
      ventricosa. The results presented here support the findings of Davis (Plant
      Physiol. 67: 825-831, 1981), but are contrary to the results of Lainson and Field
      (J. Membrane Biol. 29: 81-94, 1976).

PMID- 10089239
TI  - Mammalian amino acid transport system y+ revisited: specificity and cation
      dependence of the interaction with neutral amino acids.
AB  - A reevaluation of the specificity of system y+, the classical transporter for
      cationic amino acids is presented. System y+ has been defined as a transporter
      for cationic amino acids that binds neutral amino acids with lower affinity in
      the presence of Na+. The discovery of other transporters for cationic amino has
      suggested that some properties, originally attributed to system y+, may relate to
      other transport systems. Uncertainty concerns mainly, the affinity for neutral
      amino acids and the cation dependence of this interaction. Neutral amino acids
      (13 analogues tested) were found to bind to system y+ in human erythrocytes with
      very low affinity. Inhibition constants (Kiy, mm) ranged between 14.2 mm and >400
      mm, and the strength of interaction was similar in the presence of Na+, K+ or Li+
      (145 mm). In choline medium, no interaction was detected up to 20 mm of the
      neutral amino acid. Guanidinium ion (5 mm, osmolarity maintained with choline)
      potentiated neutral amino acid binding; the effect was most important in the case
      of l-norvaline which aligned with guanidinium ion is equivalent to arginine. This
      suggests cooperative interaction at the substrate site. The specificity of system
      y+ was shown to be clearly distinct from that of system y+L, a cationic amino
      acid transporter that accepts neutral amino acids with high affinity in the
      presence of Na+ and which influenced the classical definition of system y+.

PMID- 10089240
TI  - Epidemiology, etiology, and management of Kawasaki disease: state of the art.
AB  - Since its first description in Japan 30 years ago, Kawasaki disease has been
      reported worldwide. Although an infectious etiology is suspected based on the
      epidemiology and clinical features, a causative agent has not been identified.
      The majority of the morbidity and mortality associated with this condition is
      attributable to the development of coronary artery aneurysms. Treatment during
      the acute phase with intravenous immunoglobulin and acetylsalicylic acid results
      in significant reductions in coronary complications. The long-term management of
      patients with persistent coronary abnormalities is less well-defined. This
      article reviews the epidemiology, possible etiologies, and management of Kawasaki
      disease.

PMID- 10089241
TI  - Elevation of cardiac troponin I in the acute stage of Kawasaki disease.
AB  - The study was performed to investigate the level of serum cardiac troponin I
      (cTnI), a marker specific for myocardial damage, using a chemiluminescent
      immunoassay in the acute febrile stage of Kawasaki disease (KD). The study
      population consisted of 45 KD patients before intravenous gamma-globulin (IVGG)
      therapy and a control group of 20 patients without KD. Among KD patients the
      results from measurements of the level of cTnI were positive in 18 cases (40%)
      and the creatine kinase (CK)-MB was positive in 11 cases (24%), but in the
      control group both the cTnI and CK-MB results were negative. Seven KD patients
      (15.6%) showed increases in both cTnI and CK-MB that were significantly
      correlated with each other (p < 0.05); however, CK-MB is not heart-specific. A
      significant increase in the level of cTnI in the acute stage of KD suggests that
      acute myocarditis or myocardial cell injury begins in the early phase of the
      disease (p < 0.05). The serologic test for cTnI can thus be a useful method for
      the early diagnosis of acute myocarditis and may enable early treatment with IVGG
      to reduce the cardiovascular abnormalities in KD patients.

PMID- 10089242
TI  - Cardiorespiratory exercise tolerance in asymptomatic children with Ebstein's
      anomaly.
AB  - The aim of the study was to evaluate cardiorespiratory exercise tolerance in
      asymptomatic children with Ebstein's anomaly. Eleven children with a mean age of
      9.6 years were prospectively studied by spirometry, cardiopulmonary exercise
      testing (bicycle ergometer n = 8, treadmill test n = 3), and contrast
      echocardiography. A right-to-left atrial shunt was detected by contrast
      echocardiography in 7 children (group 1), whereas no shunt was found in 4 (group
      2). VO2 max was decreased [84.5 (SD = 16.8)] and was strongly correlated to
      oxygen saturation in group 1 (p < 0.0001). Oxygen saturation at peak uptake was
      significantly decreased compared to baseline [97.4 (SD = 2.0) vs 90% (SD = 9.5%),
      p = 0.02] and was significantly lower in group 1 than in group 2 [85.7 (2.2) vs
      98.2% (SD = 1.2%), p = 0. 03]. Oxygen desaturation was related to a right-to-left
      atrial shunt (p = 0.01). Decreased VO2 max was also correlated to the small size
      of the left ventricle (p = 0.05). We concluded that decreased exercise tolerance
      in children with asymptomatic Ebstein's anomaly is related to a right-to-left
      atrial shunt and to a small left ventricle. In case of poor exercise tolerance, a
      contrast echocardiography should be performed to detect an atrial septal defect.

PMID- 10089243
TI  - Spontaneous closure of atrial septal defects.
AB  - Atrial septal defects (ASDs) are found more frequently in the pediatric
      population than in adults, and improved diagnostic techniques with
      echocardiography (2DE) and Doppler facilitate diagnosis so that repair is
      possible at an optimal time. The purpose of our investigation was to study the
      size of ASDs at diagnosis, how size changes during follow-up, and to explore the
      relationship between size at diagnosis and need for surgery. We reviewed the
      medical records of all patients in Iceland with the diagnosis of ASD born between
      1984 and 1993. ASD was confirmed by 2DE in all patients and defects smaller than
      4 mm were excluded. ASD size was measured by 2DE from subxyphoid long and short
      axis views. There were 91 patients-29 males and 62 females. Four patients died
      from causes other than the heart defect and had not been operated upon. Seven
      patients with ASD primum and sinus venosus defects were excluded from analysis.
      There were 29 patients with a 4 mm defect, 17 patients with 5 or 6 mm defects, 8
      patients with 7 or 8 mm defects, and 26 patients had defects >8 mm. In the 4 mm
      group, in 26 patients (89%) the ASD closed spontaneously or decreased in size,
      and 1 patient had been operated upon. In the 5 or 6 mm group, 15 of 19 ASDs (79%)
      had closed spontaneously, and 2 patients (9.5%) had been operated upon. In the 7
      or 8 mm group, 1 of 6 ASDs (16.6%) had closed spontaneously and 3 had been closed
      surgically. In the >8 mm group, 1 of 24 ASDs had closed spontaneously and 20
      (91%) had been closed surgically. We conclude that defects smaller than 6 mm in
      diameter are very likely to close spontaneously although follow-up is necessary.
      Defects larger than 8 mm have a high probability requiring operative closure.

PMID- 10089244
TI  - The abnormal contralateral atrioventricular valve in mitral and tricuspid atresia
      in neonates: An echocardiographic study.
AB  - Abnormalities of the mitral valve (MV) or the tricuspid valve (TV) morphology
      and/or function in patients with functional single ventricle may result in early
      morbidity and death. The purpose of this study was to determine the incidence of
      contralateral atrioventricular valve (AVV) pathologies in mitral valve atresia
      (MA) and tricuspid valve atresia (TA). We retrospectively reviewed the
      echocardiographic data of 50 neonates with MV and 20 with TA. Appearance of the
      papillary muscles, chordae tendinae, and valve leaflets was assessed. AVV
      regurgitation was semiquantitated by color-flow Doppler and the AVV annulus
      diameter was measured and indexed to body surface area. MV abnormalities were
      found in 9 of 20 (45%) of patients with TA. The MV was myxomatous in 9 patients,
      the leaflets were redundant in 5 patients, and prolapsing occurred in 4 patients.
      Mild regurgitation was found in 2 patients. In 18 of 20 (90%) patients MV annulus
      size was larger than 95% of predicted normal values. TV abnormalities were found
      in 12 of 50 (24%) patients with MA. The TV was myxomatous in 4 patients,
      prolapsing in 2, and redundant in 3, and moderate TV regurgitation was found in 3
      patients. In 29 of 50 (58%) patients TV annulus size was larger than 95% of
      predicted normal values. Contralateral AVV abnormalities in tricuspid and mitral
      valve atresia are common and should be assessed carefully before surgical
      procedures.

PMID- 10089245
TI  - Increased arterial stiffness in children with a parental history of hypertension.
AB  - The vascular dynamics of children with a parental history of hypertension has not
      been defined. The purpose of the current study was to determine whether or not
      these children have different arterial stiffness compared to the offspring of
      normotensive parents. One hundred healthy, nonobese subjects (ages 10-21 years)
      were divided into two groups of 50. Group A included the offspring of
      hypertensive patients and group B the offspring of normotensive parents. The
      variables studied were body surface area, blood pressure, and systolic and
      diastolic diameters of the aortic and carotid arteries as well as maximum
      velocity flow of these vessels. Carotid and aortic stiffness were calculated.
      Children and adolescents with a parental history of hypertension had higher
      carotid stiffness and smaller carotid diameters. These differences continued to
      be significant when correcting for body surface area. A higher blood pressure and
      a greater body surface area were also found.

PMID- 10089246
TI  - Macro creatine kinase in Kawasaki disease.
AB  - This report describes a case of Kawasaki disease with macro creatine kinase (CK).
      A 13-month-old boy developed typical symptoms of Kawasaki disease and was treated
      with flurbiprofen, dipyridamole, and intravenous gamma-globulin. The serum level
      of CK increased during treatment from 371 U/L, at 4 days after the onset of
      Kawasaki disease, to 13,222 U/L 3 days later. Immunofixation electrophoresis
      identified macro CK as containing immunoglobulin A (kappa, lambda). The presence
      of macro CK may result from muscle tissue involvement in Kawasaki disease.

PMID- 10089247
TI  - Resolution of neonatal hypertrophic cardiomyopathy in an infant with an affected
      mother.
AB  - Hypertrophic cardiomyopathy (HCM) in infancy has been described in association
      with many medical disorders. The genetic location and mode of transmission of HCM
      in families also has been reported extensively. We present an infant with
      nonobstructive hypertrophic cardiomyopathy whose mother also had HCM. Regression
      of septal hypertrophy was documented in this patient by 1 year of age despite a
      positive family history.

PMID- 10089248
TI  - Congenital aneurysm of sinus of valsalva ruptured into right ventricle diagnosed
      by magnetic resonance imaging.
AB  - Rupture of a congenital aneurysm of the sinus of Valsalva is a rare congenital
      cardiac malformation. This case report describes a congenital aneurysm of the
      sinus of Valsalva which ruptured into the right ventricle in a 3-year-old girl.
      The exact route of the fistula through the cardiac walls and the localization of
      the rupture into the right ventricle was not completely defined by two
      dimensional and color Doppler echocardiography and could be determined only by
      magnetic resonance imaging (MRI).

PMID- 10089249
TI  - Stenting of the aorta for recurrent, long stenosis due to Takayasu's arteritis in
      a child.
AB  - Balloon angioplasty followed by stenting of the thoracic aorta is reported in a 5
      year-old girl with Takayasu's arteritis, who presented with severe hypertension
      and congestive heart failure. Her aortogram showed severe long segment stenosis
      of the descending thoracic aorta, which was successfully treated by balloon
      angioplasty on two occasions, but developed recurrences after 6 and 7 months of
      angioplasty. Balloon dilatation of the stenosed aorta, followed by sequential
      implantation of three 30-mm long Palmaz stents in tandem, bridging the full
      segment of the angioplastied aorta were performed successfully without any
      complications. The aortic diameter increased from 3.3 mm to 7.7 mm and the peak
      systolic pressure gradient decreased from 75 mmHg to 3 mmHg. There was no
      recurrence on clinical follow-up of 13 months.

PMID- 10089250
TI  - Doppler echocardiography with extended transesophageal atrial pacing: predicting
      the efficacy of permanent atrial pacing in the patient with a small left
      ventricle and sinus node dysfunction.
AB  - A 2100-g neonate underwent a two-ventricular surgical repair of a right ventricle
      dominant unbalanced atrioventricular septal defect associated with the heterotaxy
      syndrome and sinus node dysfunction. Postoperative congestive heart failure
      persisted despite bradycardia management by temporary ventricular pacing.
      Spectral Doppler echocardiographic analysis of pulmonary venous inflow and aortic
      outflow patterns demonstrated significant improvement with transesophageal atrial
      pacing. Extended transesophageal pacing was performed for two days, resulting in
      dramatic clinical improvement. This is the first report of extended
      transesophageal atrial pacing complementing Doppler echocardiography predicting
      an improved outcome with permanent atrial pacing.

PMID- 10089251
TI  - Transient left ventricular dysfunction in childhood sickle cell disease.
AB  - For unclear reasons, myocardial infarction is rare in childhood sickle cell
      disease, whereas lung, bone, and brain infarcts are more common. During
      vasoocclusive crisis and infection, acute myocardial ischemia and chronic volume
      overload from anemia may result in myocardial dysfunction. We report a child who
      had reversible cardiac dysfunction that mimicked myocardial infarction.

PMID- 10089252
TI  - Adverse hemodynamic effects observed with inhaled nitric oxide after surgical
      repair of total anomalous pulmonary venous return.
AB  - The following is a case report of a 1-month-old patient who developed adverse
      hemodynamic sequelae during the use of nitric oxide (NO) in the postoperative
      period for pulmonary hypertension after correction of total anomalous pulmonary
      venous return. At the time of diagnosis, the patient had evidence of systemic
      right ventricular pressures estimated by continuous-wave Doppler. He was sedated
      and paralyzed for hyperventilation in preparation for surgery and underwent
      pulmonary vein confluence to left atrial anastomosis. Postoperative pulmonary
      hypertension was managed by hyperventilation, sedation, and paralysis until a
      sudden onset of systemic-level pulmonary pressure required NO therapy.
      Satisfactory results were obtained in minutes, but a rebound pulmonary
      hypertension occurred with concomitant systemic hypertension and no radiographic
      changes. We suspected left atrial hypertension secondary to a sudden increase in
      pulmonary blood flow to an noncompliant left ventricle. Discontinuation of NO
      resulted in stabilization of the hemodynamic profile of the patient and he
      continued to be managed with paralysis, hyperventilation, and sedation. Based on
      this experience we suggest that NO should be used with caution in patients with
      obstructive lesions at the atrial level prior to surgery (mitral valve stenosis
      and cor triatriatum) or in patients with a poorly compliant left ventricle
      (cardiomyopathy and left ventricular dysfunction). These entities are unable to
      tolerate a sudden increase in pulmonary blood return thus creating paradoxical
      pulmonary hypertension.

PMID- 10089253
TI  - Enterococcus avium endocarditis in an infant with tetralogy of Fallot.
AB  - We report a case of infective endocarditis secondary to Enterococcus avium in a 1
      year-old infant with tetralogy of Fallot and a Blalock-Taussig shunt. To our
      knowledge, this is the first case of E. avium endocarditis to be reported.

PMID- 10089254
TI  - Pacemaker therapy in a pediatric patient with hypertrophic obstructive
      cardiomyopathy and rapid intrinsic atrioventricular conduction.
AB  - A 13-year-old boy with hypertrophic obstructive cardiomyopathy was treated with
      dual-chamber pacing after severe progression of left ventricular outflow tract
      obstruction and of clinical symptoms despite drug therapy. Rapid intrinsic
      atrioventricular conduction was overcome and complete preexcitation of the septum
      achieved by omitting atrial sensing and programming constant atrial pacing with a
      short atrioventricular delay of 70 msec. After 8 weeks of therapy, a reduction of
      the left ventricular outflow tract gradient from 125 to 16 mmHg and remodeling of
      the left ventricle were demonstrated.

PMID- 10089255
TI  - Complete atrioventricular septal defect and Ebstein's anomaly.
AB  - A case child with complete atrioventricular septal defect (AVSD) and Ebstein's
      anomaly underwent surgical treatment at 3 months of age. She died on the third
      postoperative day. Postmortem examination showed complete AVSD, downward
      displacement of the right atrioventricular valve, left ventricular outflow tract
      obstruction, and hypertensive pulmonary vascular disease. Association of complete
      AVSD and Ebstein's anomaly is a rare cardiac anomaly for which no attempt at
      surgical repair has previously been made. This report deals with our experience
      and also with the morphological features of this anomaly.

PMID- 10089257
TI  - From other journals 

PMID- 10089256
TI  - Further associations of congenital heart disease and genetic syndromes: report of
      a case of tetralogy of Fallot and Fabry's disease.

PMID- 10089258
TI  - Upcoming events in pediatric cardiology 

PMID- 10089259
TI  - Editorial 

PMID- 10089260
TI  - The effects of nutritional supplements on the treatment of depression, diabetes,
      and hypercholesterolemia in the renal patient.
AB  - The independent use of nutritional supplements has increased dramatically over
      the past several years. St. John's Wort for the treatment of depression, chromium
      for improvement of abnormal glucose and insulin regulation, and garlic for
      hypercholesterolemia, are among the more popular nutritional supplements being
      used by the population at large for their respective conditions. Depression,
      diabetes, and hypercholesterolemia are common to the renal patient. However, the
      efficacy of St. John's Wort, chromium, and garlic for these problems in the
      patient with impaired renal function is not known. This article reviews the
      pharmacology, efficacy, safety, and pharmokinetics of these three food
      supplements in the nonrenal patient. There are encouraging data suggesting
      successful treatment in the otherwise normal individual. However, clinical
      studies examining the safety of these three supplements for the treatment of
      depression, diabetes, and hypercholesterolemia in the patient with renal disease
      are lacking and preclude recommendation of their use.

PMID- 10089261
TI  - The effects of exercise during hemodialysis on physical performance and nutrition
      assessment.
AB  - OBJECTIVE: To assess the effects of participation in an intradialytic exercise
      program using commonly available measures of physical performance and parameters
      of nutrition assessment. SESIGN: Performance testing and nutrition assessment
      were completed on hemodialysis patients who participated in an in-center,
      intradialytic exercise program. Data were collected at initiation and after 3, 6,
      and 12 months of participation. One-tailed, paired t-test was used for
      statistical assessment. SETTING: Free-standing, outpatient dialysis center with
      an average of 130 patients on staff-assisted hemodialysis. PATIENTS: Data were
      collected on 16 patients who completed 3 months in the program, 6 patients who
      completed 6 months in the program, and 4 patients who completed 12 months in the
      program. INTERVENTION: Patients participated in a progressive, self-paced
      exercise program including cycling before or during hemodialysis, or walking on a
      treadmill before hemodialysis. In addition to this, patients also had the option
      of doing stretching and/or light weight exercises during hemodialysis. MAIN
      OUTCOME MEASURES: Performance tests included 60-second sit-stand, 28-ft slow and
      brisk walk, 60-second stair climb, and 60-second leg lifts. Nutrition assessment
      included changes in estimated dry weight, hemoglobin, hematocrit, serum glucose,
      calcium, phosphorus, albumin, Kt/V, normalized protein catabolic rate (nPCR),
      average monthly interdialytic weight gain, and monthly mean predialysis and
      postdialysis blood pressure. Glycohemoglobin was assessed in diabetic patients.
      Patients' charts were reviewed for episodes of intradialytic cramping and
      hypotension. RESULTS: All patients showed improvement in measures of physical
      performance at 3, 6, and 12 months. Mean phosphorus decreased from 1.94 +/- 0.45
      mmol (6.02 +/- 1.4 mg/dL) by 11% at 3 months (P = 0.05) and by 26% at 12 months
      (P < 0.02). Patients who exercised for 12 months experienced a mean 16% reduction
      in blood glucose. Mean glucose levels for 7 diabetic patients decreased from
      12.35 +/- 5.8 mmol/L (224.1 +/- 105) to 11. 66 +/- 1.9 mmol/L (211.7 +/- 34
      mg/dL); however, this was not statistically significant. Mean glycohemoglobin
      levels for diabetic patients did not change significantly. Increases were seen in
      Kt/V, estimated dry weight, and serum albumin; however, these were not
      statistically significant. Decreases were noted in mean predialysis and
      postdialysis blood pressures and average interdialytic weight gains at 3, 6, and
      12 months. CONCLUSION: A formal intradialytic exercise regimen can produce
      objective evidence of improvement in physical performance and some measures of
      nutritional well-being over 3 to 12 months. Further research is needed to
      determine if these changes are a result of exercise alone or increased compliance
      with the medical and dietary regimen.

PMID- 10089262
TI  - Visceral protein status and caloric intake in exercising versus nonexercising
      individuals with end-stage renal disease.
AB  - OBJECTIVE: To determine if differences exist in kilocalorie and protein intake
      and visceral protein levels for patients with End-Stage Renal Disease (ESRD)
      exercising during dialysis versus not exercising. DESIGN: Prospective study of 11
      patients with ESRD over a study period of 12 weeks. SETTING: Outpatient renal
      dialysis clinic. PATIENTS: Patients with ESRD undergoing hemodialysis (HD) three
      times weekly who met the following criteria were selected: aged 25 to 65 years,
      nondiabetic, no current physical activity, blood pressure of 160/95 mm Hg or less
      at the second hour of HD, no unstable angina pectoris. Eleven patients who met
      the criteria were randomized into two groups; five patients with exercise (E) and
      six patients without exercise (NE). INTERVENTIONS: From weeks 5 to 8, E patients
      began exercise during HD three times a week. Exercise gradually increased by 3
      minutes each dialysis day, maintaining 60% to 80% maximal heart rate (HR). By the
      end of week 8, all E patients reached 45 minutes of exercise, including 5 minutes
      each of warm-up and cooldown. Patients continued 45 minutes of exercise each
      dialysis day during HD at 60% to 80% maximal HR during weeks 9 through 12. NE
      patients remained sedentary throughout the study. MAIN OUTCOME MEASURE: Twenty
      four-hour dietary recalls were obtained weekly for the 12 weeks from all patients
      for kilocalorie and protein intake. Serum levels of prealbumin, transferrin, and
      predialysis and postdialysis albumin were obtained immediately before the study
      onset and at weeks 4, 8, and 12. Comments related to patients' feelings and
      exercise were recorded but not analyzed statistically. RESULTS: Analysis of
      covariance for repeated measures for kilocalories yielded no significance by
      group or over time. Mean intakes for E patients for weeks 9 through 12 were
      clinically greater than weeks 1 through 8 by approximately 200 kilocalories. The
      mean protein intake for E patients at weeks 9 through 12 (79 +/- 41 g) appeared
      clinically greater than NE patients at weeks 9 through 12 (58 +/- 11 g), although
      not statistically different. Adequacy of dialysis (Kt/V) and initial levels of
      each serum protein were covariates for analysis of variance. No statistical
      differences were found for prealbumin levels. Transferrin levels were within
      normal ranges but differed (P <.05) by group (E or NE) and time periods.
      Prealbumin and postalbumin concentrations ranged from slightly low to adequate
      levels and were different over time (P <. 05). CONCLUSION: Kilocalorie and
      protein intakes appeared to increase for E patients during the exercise program.
      No consistent increases of visceral proteins were found for E patients. A
      majority of E patients expressed feelings of improved health, better exercise
      tolerance, and improved appetite and viewed exercise as enjoyable.

PMID- 10089263
TI  - Disintegration performance of renal multivitamin supplements.
AB  - OBJECTIVE: Vitamins have traditionally been regulated as dietary supplements and
      have not been required to meet the same rigorous product quality performance
      standards as drug products. Impaired product performance, such as failure to
      disintegrate and/or dissolve in the gastrointestinal tract, could limit the
      absorption of vitamins. Furthermore, patients with renal disease have been
      reported to experience a wide range in gastrointestinal pH, which could influence
      a product's performance. The purpose of this study was to determine the effect of
      pH on the in vitro disintegration of renal multivitamin supplements. DESIGN:
      Products were studied using the United States Pharmacopeial Convention standard
      disintegration apparatus. Products were tested in simulated gastric fluid,
      neutral fluid, and intestinal fluid. Product failure was defined as two or more
      individual tablets or capsules failing to disintegrate completely within
      compendial limits. RESULTS: Of 11 products tested, 4 products failed the
      disintegration study test in all pH conditions. Sixty-four percent of the
      products showed statistically significant differences in disintegration time (DT)
      based on pH. As pH increased, time to disintegration increased. CONCLUSION: The
      DT of commercially available renal multivitamin supplements was highly variable.
      Poorest product performance was shown in simulated intestinal fluid. The pH
      significantly affected in vitro disintegration in greater than half the products
      tested. How this affects dissolution and in vivo performance has yet to be
      studied.

PMID- 10089264
TI  - Clinical indicators associated with poor oral intake of patients with chronic
      renal failure.
AB  - OBJECTIVE: The purpose of this study was twofold: (1) to determine the incidence
      of patients with chronic renal failure (CRF) who consume less than 75% of their
      estimated nutritional needs, and (2) to identify factors associated with an oral
      intake less than 75% of the estimated nutritional needs of patients with CRF.
      DESIGN: Prospective, descriptive, correlational study of data obtained from
      patients with a diagnosis of CRF. SETTING: BryanLGH Medical Center East Campus,
      Lincoln, NE. PATIENTS: Sixty-six patients included on this study met the
      following criteria: (1) a primary or secondary underlying diagnosis of CRF and
      (2) not receiving parenteral or enteral (tube feeding) nutritional support on
      admission. INTERVENTION: Admission data (age, sex, percentage of ideal body
      weight, weight loss/time, type of dialysis, gastrointestinal history, blood urea
      nitrogen and creatinine levels, and diet) were collected from the patients'
      medical records and 2-day kilocalorie (kcal)/protein counts were conducted on
      consecutive patients admitted to the hospital. The kcal/protein counts were
      initiated within 24 hours of admission and consisted of six meals and all snacks
      the patient received. MAIN OUTCOME MEASURE: Only 15% of the patients met 75% or
      greater of their estimated kcal needs, and 12% met 75% or greater of their
      estimated protein needs. The mean kcal/kg intake was 11 kcal/kg, with a range of
      0 to 27 kcal/kg, and the mean protein/kg intake was 0.42 g of protein/kg, with a
      range of 0 to 10 g of protein/kg. Of the variables studied for associations with
      decreased nutrient intake, only emesis mildly correlated with kcal intake.
      CONCLUSION: Less than one quarter of the patients on this study met 75% or
      greater of their kcal and protein needs. The average kcal and protein intakes
      found in this study were far less than current recommendations for hemodialysis,
      continuous ambulatory peritoneal dialysis, and predialysis patients. However, the
      results of this study could lead to earlier and more aggressive interventions in
      patients with CRF at risk for poor oral intake.

PMID- 10089265
TI  - The effects of moderate doses of megestrol acetate on nutritional status and body
      composition in a hemodialysis patient.
AB  - OBJECTIVE: To determine the safety and efficacy of moderate doses of megestrol
      acetate (>/=320 mg/day) in a patient on hemodialysis. DESIGN: Case study.
      SETTING: Chronic hemodialysis facility and body composition unit in New York
      City. MAIN OUTCOME MEASURES: Body weight, body composition, dietary energy and
      protein intake, appetite assessment, serum albumin, prealbumin, serum
      transferrin, and quality of life. RESULTS: The patient received megestrol acetate
      for 24 weeks and gained little body weight. However, his fat mass increased by
      7.5 kg (163%), and fat-free mass decreased by 6.8 kg (10.6%) from baseline
      measurements. The proportional content of total body water, extracellular water,
      intracellular water, body cell mass in fat-free mass, and average cell K+
      concentration were maintained within normal ranges. Serum albumin was maintained,
      serum transferrin increased, prealbumin decreased, dietary energy and protein
      intakes increased, and reported appetite improved. CONCLUSIONS: Moderate doses of
      megestrol acetate may be an effective therapeutic agent in reversing poor
      appetite, increasing dietary energy and protein intakes, and improving
      nutritional status in some patients receiving maintenance hemodialysis. However,
      these changes were at the expense of altering body composition components.
      Further research that includes measures of body composition, nutritional status,
      appetite assessment, and quality of life are needed to determine the safety and
      effectiveness of moderate or high doses of megestrol acetate in a large number of
      hemodialysis patients.

PMID- 10089266
TI  - Clinical outcome of calcitriol therapy and patient education program on
      hyperparathyroidism.
AB  - The treatment of patients with hyperparathyroidism provides a challenge for the
      dialysis team. Interventions with calcitriol therapy, phosphate binders,
      motivational efforts, and education on diet and renal osteodystrophy can help to
      control parathyroid hormone (PTH). Effects of intervention were studied on 54
      hemodialysis patients for 1 year, resulting in improved outcomes.

PMID- 10089268
TI  - Reflections and Changes.

PMID- 10089267
TI  - Your renal guide to the new food label.

PMID- 10089269
TI  - Outcomes and Genes.

PMID- 10089270
TI  - Diagnostic Detection and Direct Genotyping of Borrelia burgdor feri Regular by
      Polymerase Chain Reaction in Cerebrospinal Fluid in Lyme Neuroborreliosis.
AB  - Background: A DNA target imbalance in favor of the plasmid-borne outer surface
      protein A (OspA) versus chromosomal genes has been thought to explain the
      relatively high diagnostic sensitivity of an OspA-based polymerase chain reaction
      (PCR) on joint fluid from patients with Lyme arthritis. The aim of this study was
      to evaluate the diagnostic sensitivity of the OspA-based PCR on cerebrospinal
      fluid (CSF) samples from patients with Lyme neuroborreliosis and to perform DNA
      sequence analysis on the amplicon to determine the genospecies of Borrelia
      present in the CSF. Methods and Results: CSF from 150 consecutively diagnosed
      European patients with untreated active neuroborreliosis was investigated.
      Borrelia burgdorferi DNA was detected in 31 of 150 patients with Lyme
      neuroborreliosis (20.6%). Genotyping of the amplicons was possible in 13 of the
      CSF samples and revealed that 11 of the 13 patients had been infected with
      Borrelia garinii, 1 with Borrelia afzelii, and 1 specimen showed evidence of a
      mixture of B. garinii and B. afzelii sequences. Conclusions: The diagnostic
      sensitivity of the OspA-based PCR for detection of B. burgdorferi DNA in CSF was
      comparable to that found previously using PCR assays based on genomic targets.
      The predominance of B. garinii DNA (92%) found in CSF substantially supports the
      current hypothesis that B. garinii is the principal agent of Lyme
      neuroborreliosis in Europe. Mixed infections, comprising different genospecies of
      B. burgdorferi sensu lato, seem to be the exception.

PMID- 10089271
TI  - Can Different Thyroid Tumor Types Be Distinguished by Polymerase Chain Reaction
      Based K-ras Mutation Detection?
AB  - Background: Thyroid tumors have mutations of the ras oncogenes, although the
      prognostic and diagnostic significance of this remains unclear. Usually, thyroid
      follicular adenoma, follicular carcinoma, and papillary carcinoma are easy to
      differentiate histologically. Occasionally, follicular carcinoma may be difficult
      to separate from the follicular variant of papillary carcinoma, and a molecular
      test to help differentiate the two would be critical, as their behavior and
      clinical management differ. In earlier reports, K- ras mutations have been
      suggested as such a marker. Methods and Results: To study genetic differences
      between thyroid tumors, the authors examined 79 cases (58 papillary carcinomas,
      12 follicular carcinomas, and 9 adenomas) for the presence of a K-ras mutation in
      codon 12 by polymerase chain reaction and restriction endonuclease digestion.
      Only six papillary carcinomas (12%) showed a K-ras mutation; no mutations were
      detectable in the other thyroid tumors. Conclusion: K-ras mutation analysis does
      not help differentiate thyroid tumor types.

PMID- 10089272
TI  - Detection of Breast Cancer Cells in Blood Using Immunomagnetic Bead Selection and
      Reverse Transcription-Polymerase Chain Reaction.
AB  - Background: A sensitive and specific method for the detection of occult breast
      cancer cells may prove clinically useful. The purpose of this study was to
      investi gate cytokeratin-19 (CK-19) and gross cystic disease fluid protein
      (GCDFP) as potential reverse transcription-polymerase chain reaction (RT-PCR)
      targets for the detection of breast micrometastases. Through positive selection
      of breast epithelial cells by immunomagnetic bead separation, two RT-PCR assays
      were developed. Methods and Results: Positive selection of breast epithelial
      cells was performed using Ber-EP4 monoclonal antibody bound to magnetic beads.
      RNA was isolated and RT-PCR performed using CK-19 and GCDFP as targets. Detection
      sensitivity was five T47D cells spiked into 10 mL of normal blood for either
      target. In all, 100% (3 9/39) of normal bloods were negative for CK-19, whereas
      only 87% (34/39) were negative with GCDFP. In 15 patients with metastatic disease
      including 3 without treatment and 12 on either tamoxifen or chemotherapy, CK-19
      was positive in 67% (10/15) of patients and GCDFP yielded positives in 27% (4/15)
      of patients tested. Conclusions: The detection of CK-19 and GCDFP in bloods from
      patients with metastatic breast cancer may be beneficial in determining the
      course of therapy, as well as having potential prognostic and diagnostic
      applications. Although CK-19 appears to be the more sensitive and specific
      marker, further investigation with both targets is warranted.

PMID- 10089273
TI  - An Unexpected Product From Polymerase Chain Reaction-Mediated Site-Directed
      Mutagenesis Due to Misalignment of the Mismatched Primer.
AB  - Background: The I1307K (T3920 --> A) variant of the APC gene has been identified
      as a potential risk factor for colorectal cancer and is present in 6% of
      Ashkenazi Jews. Screening for this mutation may allow identification of people at
      elevated risk who would benefit from increased surveillance. Methods and Results:
      We designed an assay to detect the T3920 --> A allele using a primer mismatched
      at the 3 < 9 terminal nucleotide in the polymerase chain reaction (PCR) to
      generate a recognition site for the restriction enzyme Mse I. After optimization
      of the PCR for magnesium ion concentration and annealing temperature, the
      amplicon did not cut completely with the restriction enzyme in each of four
      tested DNAs. Sequence analysis of the PCR product that was resistant to digestion
      revealed that the T3920 --> A variant was not present. The artifact was caused by
      a single nucleotide loop-out in the genomic DNA template under the 3 < 9 region
      of the primer, which allowed the 3 < 9 terminal base of the primer to hybridize
      properly. As a result, the mismatched primer created a modified product different
      from that originally planned. At a magnesium ion concentration below the optimum
      for product yield, most of the product was digested by Mse I. Sequence analysis
      showed that, under these conditions, the intended product was produced.
      Conclusions: Mismatched primers can produce unintended products in a PCR due to
      looping out of a nucleotide in the template or the primer. The magnesium ion
      concentration can influence the sequence and amount of the product.

PMID- 10089274
TI  - Blastic Transformation in a Case of Hairy Cell Leukemia.
AB  - Background: Hairy cell leukemia (HCL) is a slowly progressive lymphoproliferative
      disorder that tends to afflict middle-aged adults, especially men. Blastic
      transformation of this form of leukemia is extremely rare. To date, a single case
      has been reported. Methods and Results: A case of HCL, evolving with blastic
      transformation after a 9- year clinical course, is reported. Routine histology,
      cytochemistry, flow cytometry immunophenotyping, and Southern blot analysis for B
      and T-cell gene rearrangements were used in the evaluation. Although morphology
      at the time of presentation was characteristic of HCL, the cells were initially
      tartrate-resistant acid phosphatase (TRAP) negative. During a clinical course
      over several years, the hairy cells became progressively TRAP positive. The
      morphology of the leukemic cells changed 9 years after initial diagnosis, with
      blastic transformation and retaining strong TRAP positivity. Immunophenotypic
      analysis showed evolution from a characteristic hairy cell leukemic phenotype to
      a phenotype indicative of marked immaturity. Genotypic analysis showed an
      evolving pattern of immunoglobulin gene rearrangements, paralleling the
      morphology and phenotypic evolution and ruling out a second B-cell malignancy.
      Conclusions: This case report of blastic transformation in a patient with HCL is
      only the second such case identified in the medical literature to date.

PMID- 10089275
TI  - Analysis of Four Common Salt-Wasting Mutations in CYP21 (Steroid 21-Hydroxylase)
      by Cleavase Fragment Length Polymorphism Analysis and Characterization of a
      Frequent Polymorphism in Intron 6.
AB  - Background: Congenital adrenal hyperplasia (CAH) owing to steroid 21-hydroxylase
      deficiency results from mutations in CYP21. The majority of patients with this
      disorder have salt-wasting because of mineralocorticoid deficiency, and most
      patients with salt-wasting have one of four common mutations: deletions of CYP21,
      or nondeletion mutations including a 3 < 9 premature splice mutation in intron 2;
      an 8-bp deletion in exon III; a cluster of mutations in exon VI; and R356W.
      Methods and Results: The authors analyzed these mutations using a new mutation
      detection methodology, cleavase fragment length polymorphism (CFLP) analysis. All
      of these mutations were detectable using CFLP. The intron 2 splice mutation, exon
      III 8-bp deletion, and R356W mutation all resulted in novel CFLP bands not seen
      in subjects without those mutations. The exon VI cluster of mutations resulted in
      elimination of a CFLP band, which was easily detected in a patient with that
      mutation and a gene deletion on the homologous chromosome. The authors also
      report the characterization of a restriction fragment length polymorphism in
      intron 6 involving the RsaI site around nucleotide 1419. In 48 chromosomes from
      the parental generation of the Centre d'Etude du Polymorphisme Humain families,
      the frequency of the polymorphism that destroys the RsaI site was found to be
      12.5%. Conclusions: CFLP is a potentially useful analytic method for analyzing
      frequent CYP21 mutations that cause salt-wasting CAH, although further
      development of the technique is required to clearly distinguish heterozygotes
      from homozygotes for mutations that generate novel CFLP bands and to identify
      heterozygotes for mutations that eliminate a CFLP band. The Rsa I polymorphism
      may be a useful marker for following the segregation of CYP21 alleles in genetic
      studies and is of use in showing gene deletions of CYP21 in informative families.
      The polymorphism may also be of use in genetic studies of the human major
      histocompatibility complex.

PMID- 10089276
TI  - Laboratory Medicine and the Advancing Technology Paradigm.

PMID- 10089277
TI  - On Common Ground.

PMID- 10089278
TI  - Detection and Identification of Base Alterations Within the Region of Factor V
      Leiden by Fluorescent Melting Curves.
AB  - Background: Factor V Leiden (G1691A) is a common cause of inherited thrombosis.
      In fluorescent melting curve analysis, the Leiden mutation is distinguished from
      the wild-type by a decrease in melting temperature (Tm) of a wild-type probe.
      Because Tm depends on the type and position of the mismatch, other base
      alterations, such as the recently described base alteration A1692C, should be
      distinguishable from the true Leiden mutation. Methods and Results: Of 2,100
      samples tested for the factor V Leiden mutation using a wild-type probe, 200
      heterozygous or homozygous mutant samples were further tested using a Leiden
      probe. The Tm of the A1692C base alteration was 1.5 degrees C greater than the
      Leiden mutation with the wild-type probe and 8 degrees C less with the Leiden
      probe. One sample was heterozygous for a new base alteration G1689A with a Tm 0.8
      degrees C greater than the Leiden mutation with the wild-type probe, and 10
      degrees C less with the Leiden probe. Tm estimates from fluorescence melting
      curve analysis have intra-assay standard deviations of approximately 0.1 degrees
      C. Conclusions: Fluorescence melting curve analysis can distinguish between
      sequence alterations with Tms differing by less than 1 degrees C. This is the
      first demonstration of a widely applicable technique that can significantly
      increase the specificity of hybridization techniques without the need for
      sequencing.

PMID- 10089279
TI  - A False-Positive Diagnosis for the Common MELAS (A3243G) Mutation Caused by a
      Novel Variant (A3426G) in the ND1 Gene of Mitochondria DNA.
AB  - Background: Several mutations in mitochondrial DNA (mtDNA) are associated with
      the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes (MELAS). The "common" MELAS mutation, A3243G in the tRNA
      leucine (UUR) gene, affects approximately 80% of cases and is associated with
      respiratory chain complex I deficiency. Methods and Results: The A3243G mutation
      creates an ApaI restriction endonuclease site and can be detected by polymerase
      chain reaction (PCR) amplification of a region of mtDNA containing nt 3243,
      followed by ApaI digestion and electrophoretic analysis of the resulting
      fragments. Analysis of mtDNA from a child with complex I deficiency indicated the
      presence of the mutation homoplasmically in heart, liver, and skeletal muscle.
      Sequencing revealed only normal tRNA leucine (UUR) sequence, and a novel variant
      at nt 3426 in the ND1 subunit of complex I, which creates an ApaI site. ApaI
      digestion results in fragments of similar size to those found in patients with
      the A3243G mutation. Conclusions: A novel variant at nt 3426 of mtDNA creates an
      ApaI site and can potentially cause a false-positive result for the presence of
      the A3243G mutation. Given the highly polymorphic nature of mtDNA, care must be
      exercised in choosing primers for restriction endonuclease-based diagnostic tests
      for point mutations, and confirmation of a mutation by an independent method is
      recommended.

PMID- 10089280
TI  - Direct Fluorescence Detection of Allele-Specific PCR Products Using Novel Energy
      Transfer Labeled Primers.
AB  - Background: Currently analysis of point mutations can be done by allele-specific
      polymerase chain reaction (PCR) followed by gel analysis or by gene-specific PCR
      followed by hybridization with an allele-specific probe. Both of these mutation
      detection methods require post-PCR laboratory time and run the risk of
      contaminating subsequent experiments with the PCR product liberated during the
      detection step. The author has combined the PCR amplification and detection steps
      into a single procedure suitable for closed-tube analysis. Methods and Results:
      Allele-specific PCR primers were designed as Sunrise energy-transfer primers and
      contained a 3' terminal mismatch to distinguish between normal and mutant DNA.
      Cloned normal (W64) and mutant (R64) templates of the beta3-adrenergic receptor
      gene were tested to verify amplification specificity and yield. A no-target
      negative control was also run with each reaction. After PCR, each reaction was
      tested for fluorescence yield by measuring fluorescence on a spectrofluorimeter
      or fluorescent microtitreplate reader. The cloned controls and 24 patient samples
      were tested for the W64R mutation by two methods. The direct fluorescence results
      with the Sunrise allele-specific PCR method gave comparable genotypes to those
      obtained with the PCR/ restriction digest/gel electrophoresis control method. No
      PCR artifacts were observed in the negative controls or in the PCR reactions run
      with the mismatched target. Conclusions: The results of this pilot study indicate
      good PCR product and fluorescence yield from allele-specific energy-transfer
      labeled primers, and the capability of distinguishing between normal and mutant
      alleles based on fluorescence alone, without the need for restriction digestion,
      gel electrophoresis, or hybridization with an allele-specific probe.

PMID- 10089281
TI  - Duplex PCR for Autosomal Dominant Spinocerebellar Ataxia Testing: A
      Nonradioactive Rapid Screening Method.
AB  - Background: Current DNA diagnostic testing for spinocerebellar ataxias (SCAs) 1,
      2, 3, and 6 involves four separate tests based on radioactively-labeled poly
      merase chain reaction (PCR). Although this approach allows accurate allele
      sizing, it also is time-consuming and requires manipulation with hazardous
      radioactive isotopes. Methods and Results: A rapid screening approach was
      developed based on a nonradioactive and duplexed PCR assay coupling SCA 1 and SCA
      3 together and SCA 2 and SCA 6 together. This was achieved by designing new
      primers that amplify all normal and mutant alleles in nonoverlapping size ranges.
      A series of negative and positive samples previously tested with the single
      radioactively labeled PCRs was tested using the new duplex PCRs; 100% concordancy
      was achieved. Conclusion: This novel approach of nonradioactive, duplex PCRs for
      autosomal dominant spinocerebellar ataxias is a rapid, reliable, and cost
      effective diagnostic screening approach that is suitable for laboratories with
      high sample load and/or laboratories seeking to reduce their use of
      radioisotopes.

PMID- 10089282
TI  - Novel pncA Mutations in Pyrazinamide-Resistant Isolates of Mycobacterium
      tuberculosis.
AB  - The gene coding for pyrazinamidase (PZase) activity, pncA, in Mycobacterium
      tuberculosis was recently cloned, and several mutations which correlate with in
      vitro resistance to pyrazinamide (PZA) have been identified. During the
      development of a clinical molecular assay for the detection of PZA resistance,
      two previously unreported mutations in isolates of PZA-resistant M. tuberculosis
      were identified. The assay that uses automated DNA sequencing is relatively rapid
      and allows the detection of any mutations present in the coding region of the
      pncA gene. The new mutations are both point mutations resulting in amino acid
      substitutions; 241T --> G results in F80V, and 511G --> C results in A171P. The
      identification of these mutations accentuates the utility of automated DNA
      sequencing in the clinical laboratory.

PMID- 10089283
TI  - Detection of Monoclonality in South African T-Cell Lymphoma Cases Using PCR
      Analysis of T-Cell Receptor-gamma Gene Rearrangements.
AB  - Background: The polymerase chain reaction (PCR) has become a useful method to
      determine monoclonality in T-cell lymphomas. The authors investigated a number of
      T-cell lymphoma cases to determine (1) the monoclonality detection rate in South
      African T-cell lymphoma cases and (2) whether variation in detection of
      monoclonality exists in T-cell lymphoma subtypes. Methods and Results: Thirty T
      cell lymphoma cases, including pleomorphic peripheral T-cell lymphomas, precursor
      T-lymphoblastic lymphomas, large-cell anaplastic lymphomas, and one cutaneous
      lymphoma, were assessed. DNA was purified from paraffin-embedded tissue and
      amplified with consensus oligonucleotide primers directed at the rearranged T
      cell receptor-gamma genes. Monoclonality was found in 73% of cases, similar to
      previous reports. Pleomorphic peripheral T-cell lymphomas (89%) were detected
      most successfully; lymphoblastic (73%) and large-cell anaplastic lymphomas (58%)
      had lower detection efficiencies. Conclusions: Some T-cell lymphoma subtypes are
      less successfully detected; additional primer sets should be used to improve
      detection.

PMID- 10089284
TI  - Identification of Mutations Causing 6-Pyruvoyl- Tetrahydrobiopterin Synthase
      Deficiency in Polish Patients With Variant Hyperphenylalaninemia.
AB  - Background: 6-Pyruvoyl-tetrahydrobiopterin synthase (PTPS) is required for
      biosynthesis of tetrahydrobiopterin, the cofactor of various enzymes including
      the hepatic phenylalanine hydroxylase. Mutations in the PTS gene result in a
      variant type of hyperphenylalaninemia, requiring cofactor replacement therapy for
      treatment. Methods and Results: Four Polish patients with PTPS deficiency were
      screened for mutations in the PTS gene. Three novel mutations E35G, N36K, and
      F100V were identified. In one patient, a known mutation D136V was identified in
      both PTS alleles. Conclusions: Mutation D136V present in both alleles was
      proposed to be connected with a mild form of PTPS deficiency. The other three
      mutations were found in heterozygous patients with a central type of PTPS
      deficiency. D136V mutation is a common mutation in the Polish population.

PMID- 10089285
TI  - Micro Diagnostics Meets Molecular Diagnostics At 30th Annual Oak Ridge
      Congerence.

PMID- 10089286
TI  - Characterization of potential NMDA and cholecystokinin antagonists I. acid-base
      properties of 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxylic acids at the
      molecular and submolecular levels.
AB  - The protonation macroconstants (log K) of 4(3H)-quinazolone (1) and two 2-methyl
      4-oxo-3H-alkyl-quinazoline-3-carboxylic acid derivatives (2,3) were determined by
      pH-potentiometry. The acid-base chemistry of compounds 2 and 3, where proton
      bindings take place in an overlapping fashion, was described in terms of
      protonation microconstants as well. Microspeciation was carried out by two means:
      UV-pH titration (selective, pH-dependent monitoring of the N1-binding site), and
      deductively (using a derivative compound as covalently fixed model of one of the
      protonation isomers). The microconstant values obtained by the two different
      methods are in agreement within 0.05 log K units. Microspeciation revealed
      remarkable differences between the two homologue compounds (2 and 3). The
      microconstant values show that insertion of a second methylene moiety into the
      aliphatic acid side-chain (1) increases the electron-density and most basicity
      parameters of both functional groups; (2) significantly modifies the extent of
      site-site interactions in the molecule; (3) opens new conformational preferences
      by N1 ring nitrogen-carboxylic group intramolecular hydrogen bond formation and
      (4) reverses the predominantly zwitterion-involved protonation pathway into a
      neutral form-involved pathway. These molecules exemplify that microconstant
      values allow the comparative prediction and quantitative evaluation of
      pharmacokinetic behaviour, and signify the fact that microspeciation is a
      powerful tool in the process of drug development.

PMID- 10089287
TI  - Characterization of potential NMDA and cholecystokinin antagonists. II.
      Lipophilicity studies on 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxylic acid
      derivatives.
AB  - The lipophilicity of 17 newly synthesized potential NMDA and cholecystokinin
      antagonist 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxylic acid derivatives has
      been investigated. The apparent partition coefficients of two amphoteric
      compounds of overlapping protonation (Q1 and Q2) were determined by shake-flask
      method and converted into true log P values using the protonation microconstants.
      The difference between their lipophilicity expressed with the true partition
      coefficients was less, than it could be expected from the 2D structures and was
      explained with conformational preferences and formation of intramolecular
      interactions. Out of the other 15 monoprotic quinazolone compounds the
      lipophilicity of ten molecules (Q8-Q17, experimental set) was determined by TLC
      method with the help of a calibration set consisting of 12 standard molecules,
      five quinazolones (Q3-Q7) and seven pyrido[1,2-a]pyrimidines (PP1-PP7). In order
      to justify the suitability of pyrido-pyrimidines as standards for the
      chromatographic log P determination of quinazolones, first Q3-Q7 were examined by
      TLC and HPLC using PP1-PP7 for calibration. Data showed good agreement of results
      obtained by shake-flask and two different chromatographic methods indicating the
      similar chromatographic behavior of the two bicyclic systems and the relevance of
      PP1-PP7 to extend the calibration set of quinazolones. The obtained log P values
      proved mostly the expected structure-activity relationships. Some findings,
      however, have revealed specific partition behavior of the compounds providing
      useful information in the estimation of their pharmacokinetics, and these are
      discussed in the paper.

PMID- 10089288
TI  - Dynamic dialysis for the drug release evaluation from doxorubicin-gelatin
      nanoparticle conjugates.
AB  - The drug release from doxorubicin (DXR)-gelatin nanoparticle conjugates was
      evaluated by means of a dynamic dialysis technique. The study was carried out in
      absence and in presence of a proteolytic enzyme (trypsin) able to degrade the
      carrier. In a preliminary study the apparent permeability constant (Kcv) of the
      drug through the dialysis bag was evaluated in several media. On the basis of
      this screening, a saline solution (NaCl 0.9%, w/v) resulted appropriate to carry
      out the dialysis study since, in this medium, the Kcv did not depend on the drug
      concentration in the donor solution. In absence of the enzyme only a little
      fraction (from 9 to 13%, w/w of the drug content) was released from
      nanoparticles. This fraction was considered as the evidence of the free drug
      fraction. After the addition of trypsin, the diffusion of a further drug fraction
      was observed. This fraction is probably due to a fraction of the DXR-peptide
      conjugates characterised by a molecular weight lower than membrane cut-off (3500
      Da).

PMID- 10089289
TI  - Enzymatic degradation of SLN-effect of surfactant and surfactant mixtures.
AB  - Solid lipid nanoparticles (SLN) show different degradation velocities by the
      lipolytic enzyme pancreatic lipase as a function of their composition (lipid
      matrix, stabilizing surfactant). In combination with pancreatic colipase a
      degradation assay has been developed for studying the degradation behavior. As a
      measure to follow the degradation the formed free fatty acids have been analyzed
      using an enzymatic test. In the studies SLN degradation showed dependencies in
      relation to the length of the fatty acid chains in the triglycerides and the
      surfactants used for SLN production. The longer the fatty acid chains in the
      glycerides, the slower the degradation. The influence of surfactants can be
      degradation accelerating (e.g. cholic acid sodium salt) or a hindering,
      degradation slowing down effect due to steric stabilization (e.g. Poloxamer 407).
      As a second steric stabilizer, Tween 80 has been used and the results showed a
      less pronounced effect on hindering the degradation process than for Poloxamer
      407. This result seems to be correlated to the number of ethyleneoxide chains in
      the molecule. The longer the ethyleneoxide chains are in the molecule, the more
      hindered is the anchoring of the lipase/colipase complex and consequently the
      degradation of the SLN. The result can be used to adjust degradation of SLN and
      consequently drug release in a controlled way.

PMID- 10089290
TI  - Comparison of the IV pharmacokinetics in sheep of miconazole-cyclodextrin
      solutions and a micellar solution.
AB  - The pharmacokinetics of miconazole were studied after intravenous administration
      to six sheep (4 mg/kg) of three aqueous solutions: a marketed micellar solution
      containing polyoxyl-35 castor oil (Daktarin IV(R)) was compared with two
      solutions both containing 50 mM lactic acid and a cyclodextrin derivative (100 mM
      HP-betaCD or 50 mM SBE7-betaCD). The aim of this work was to demonstrate that
      these cyclodextrin derivatives (CDs) have no effect on the pharmacokinetics of
      miconazole by comparison with the micellar solution. The plasma concentration
      time curves have shown that there is no significant difference between the three
      solutions.

PMID- 10089291
TI  - An in-vitro method for buccal adhesion studies: importance of instrument
      variables.
AB  - A method using a texture analyzer equipment and chicken pouch as the biological
      tissue was investigated for measuring the bioadhesive properties of polymers
      under simulated buccal conditions. The method was evaluated using two polymers,
      namely Carbopol 974P and Methocel K4M while the instrument variables studied
      included the contact force, contact time and speed of withdrawal of the probe
      from the tissue. The parameters measured were the work of adhesion and peak
      detachment force. Longer contact time and faster probe speed not only gave better
      reproducibility of results, but also better sensitivities for both parameters
      measured. On the other hand, a certain level of contact force was found essential
      for achieving good bioadhesion, above which there was no further contribution to
      the bioadhesion process. When the method was applied to determine the
      bioadhesiveness of several polymers, the values obtained for the work of adhesion
      and peak detachment force were quite consistent in the ranking of the polymers.
      The Carbopols were found to have the highest values, followed by gelatin, sodium
      carboxymethyl celluloses and hydroxypropylmethyl celluloses. On the other hand,
      Alginic acid, Eudragit RLPO and RSPO, and Chitosan appeared to have low
      bioadhesive values.

PMID- 10089292
TI  - The transport of polymeric microspheres across the ciliated epithelia of the
      bullfrog.
AB  - The influence of some hydrophilic polymers on the clearance of particles across
      the ciliated epithelium of the bullfrog palate has been examined. The polymers
      studied were Carbopol 907 cross-linked with maltose to provide microspheres of
      varying cross-link density, Carbopol 934P, hydroxypropylmethylcellulose, chitosan
      and poly(vinyl alcohol). Transport rates were determined relative to glass
      spheres. The polymers in dilute solution (0.1 and 0.5% w/v) resulted in a
      reduction in the transport rate of the glass spheres. For non-cross-linked
      microspheres, Carbopol 934P exhibited a lower transport rate than the more slowly
      hydrating chitosan. The cross-linked poly(acrylic acid) microspheres showed
      clearance rates which were dependent on the cross-link density. Incorporation of
      some preservatives (EDTA, methylhydroxybenzoate, chlorbutol and chlorocresol),
      known to reversibly retard clearance, into the cross-linked poly(acrylic acid)
      microspheres produced effects dependent on cross-link density: lightly cross
      linked microspheres were cleared more slowly than the preservative-free
      microspheres whilst for more heavily cross-linked particles the converse was
      observed.

PMID- 10089293
TI  - Protein binding of some nonsteroidal anti-inflammatory drugs studied by high
      performance liquid affinity chromatography.
AB  - The protein binding of indomethacin, sulindak and diclofenac sodium is studied in
      the presence of some competitors: phenylbutazon and diazepam. A high-performance
      liquid affinity chromatography based on chiral stationary phases with immobilized
      human serum albumin is used. The competition of the markers and the drugs for two
      major high- and low-affinity binding sites is investigated. Using a mathematical
      procedure proposed by the same authors in a previous work the affinity constants
      of the binding drugs and markers for both types of site are calculated. An
      analogous behaviour is established for the three drugs-they have nearly the same
      affinity for the primary binding sites marked by phenylbutazon and diazepam and
      only one type of low-affinity site (diazepam-binding sites) is involved in
      binding. That can be explained assuming an overlapping sites.

PMID- 10089294
TI  - Pharmacodynamics of insulin in polyethylene glycol-coated liposomes.
AB  - To reduce the injection frequency and toxicity of intravenously administered
      protein drugs, it is necessary to develop safe and sustained injectable delivery
      systems. In this study, to evaluate liposomes as safe and sustained injectable
      delivery systems of proteins, we chose insulin as a model protein drug and tested
      its incorporation efficiency and pharmacodynamics in various liposomes with and
      without polyethylene glycol (PEG)-derivatized phospholipid. The liposomes coated
      with PEG showed 3-fold higher efficiency of insulin incorporation than did the
      liposomes without PEG. Moreover, among the liposomes coated with PEG,
      dipalmitoylphosphocholine (DPPC) liposomes showed higher incorporation efficiency
      than did dimyristoylphosphocholine (DMPC) liposomes. For pharmacodynamic study,
      insulin (2 IU/kg) was administered in various formulations, such as insulin alone
      in phosphate-buffered saline and insulin in the DPPC liposomes with and without
      PEG, to streptozotocin-treated diabetic rats. The pharmacodynamics of insulin
      alone, however, could not be measured due to the immediate death of rats caused
      by hypoglycemic shock. In contrast, all the rats treated with liposomal insulin
      survived, probably by the sustained release of insulin from liposomes.
      Pharmacodynamics of liposomal insulin showed that PEG-coated liposomes induced
      the lowest level of blood glucose-the nadir-1 h later than did the liposomes
      without PEG. These results indicate that PEG-coated liposomes could be developed
      as a relatively safe and sustained injectable delivery system for insulin with
      improved incorporation efficiency. Moreover, it is suggested that the liposomes
      coated with PEG might have a potential as safe injectable delivery systems for
      other protein and peptide drugs.

PMID- 10089295
TI  - Characterisation of the glass transition of HPMC using modulated temperature
      differential scanning calorimetry.
AB  - The glass transitional behaviour of HPMC powder and film samples has been studied
      using modulated temperature differential scanning calorimetry (MTDSC) in order to
      explore the ability of the technique to detect transitions which involve small
      changes in heat capacity. HPMC E4M Prem samples were studied in both powder and
      film form using a TA Instruments MDSC 2920 using a range of pans, modulation
      amplitudes and underlying heating rates. Moisture contents were measured using a
      TA Instruments TGA 2950. Studies on HPMC powder demonstrated the greater clarity
      with which the glass transition, seen at approximately 162 degrees C, may be seen
      using MTDSC compared to conventional DSC. The practical difficulties associated
      with casting suitable HPMC films are discussed, with similar results for Tg being
      found for hermetically sealed pans and pin-holed pans. Increasing the modulation
      amplitude from 0.212 to 0.5 degrees C improved the signal to noise ratio and
      increased the magnitude of the measured Tg. Increasing the underlying heating
      rate from 2 to 5 degrees C/min also improved the signal. The study has outlined
      several features which need to be considered in association with the measurement
      of HPMC glass transitions using MTDSC; these include the method of sample
      preparation, the choice of pans, the modulation amplitude and the underlying
      heating rate.

PMID- 10089296
TI  - Microviscosity of hydroxypropylcellulose gels as a basis for prediction of drug
      diffusion rates.
AB  - This study investigated the influence of the rheological properties of
      hydroxypropylcellulose (HPC) gels on the in vitro release of theophylline
      included in the gel at 0.2 g/l. Experiments were performed with six HPC varieties
      (mean molecular weight between 5x105 and 1.2x106, nominal viscosity between 100
      and 4000 mPa.s) at concentrations of 0-2% (w/w). Theophylline diffusion
      coefficients at 37 degrees C ranged from 3.5x10-7 to 1.1x10-3 cm2/min, and were
      in all cases markedly higher than those predicted on the basis of gel
      macroviscosity as determined by capillary viscometry. In general, the
      theophylline diffusion coefficient declined exponentially with HPC concentration;
      in the case of the lowest-molecular-weight HPC, however, the diffusion
      coefficient remained constant to HPC concentrations of up to 0.8%, probably
      because of the high entanglement concentration of the HPC. Gel microviscosities
      as determined by dynamic light scattering (DLS) with latex microspheres (162 nm
      diameter) were considerably lower than the macroviscosities determined by
      capillary viscometry, and similar to microviscosities estimated on the basis of
      theophylline diffusion. Nevertheless, macroviscosity was correlated with
      microviscosity, suggesting that it is of value for approximate estimates of rates
      of diffusion of theophylline from HPC gels.

PMID- 10089297
TI  - Degradation of hydroxypropylcellulose by Rhizomucor: effects on release from
      theophylline-hydroxypropylcellulose tablets.
AB  - The stability of several varieties of hydroxypropylcellulose was monitored during
      3 years of storage (1) under the conditions recommended by manufacturers and
      official pharmacopoeias (simple storage in closed containers) and (2) at zero
      relative humidity. After 1 year, severe degradation of the varieties with lower
      initial pH and particle size stored at ambient relative humidity was shown by
      changes in their molecular weight and in the pH and apparent viscosity of 2%
      aqueous dispersions. Microbiological analyses showed the observed degradation to
      be attributable to the action of fungi of the genus Rhizomucor. The changes in
      apparent viscosity significantly affected the release of theophylline from direct
      compression tablets formulated with the degraded excipients.

PMID- 10089298
TI  - Exposure of hemodialysis patients to di-2-ethylhexyl phthalate.
AB  - The migration of di-2-ethylhexyl phthalate (DEHP) from dialyzers was studied in
      21 patients with chronic renal failure undergoing maintenance hemodialysis. The
      circulating concentrations of DEHP were measured by high performance liquid
      chromatography in blood of patients obtained from the inlet and the outlet of the
      dialyzer during a 4-h dialysis session. During treatment of renal failure using
      plasticized tubing, the plasma level of DEHP increased. On average, an estimated
      75.2 mg of DEHP was extracted from the dialyzer during a single dialysis session,
      with a range of 44.3-197. 1 mg. On the other hand, the total amount of DEHP
      retained by the patient during the dialysis session was evaluated by the
      difference between the AUCout and the AUCin and ranged from 3.6 to 59.6 mg. The
      rate of extraction of DEHP from the dialyzer was correlated (r=0.705, P<0.05)
      with serum lipid content (cholesterol and triglyceride).So, we confirmed that
      patients on hemodialysis are always regularly exposed to considerable amounts of
      DEHP. However, several metabolic effects have been reported in various animal
      species following treatment with DEHP, such as changes in lipid metabolism and in
      hepatic microsomal drug-metabolizing enzyme activities. DEHP is now a well-known
      hepatic peroxisomal proliferator in rodents and an inducer of many peroxisomal
      and non-peroxisomal enzymes. So, lipid metabolism modifications and hepatic
      changes observed in hemodialysis patients could be explained from chronic
      exposition to DEHP. In the coming years, it seems necessary to reconsider the use
      of DEHP as a plasticizer in medical devices. Highly unacceptable amounts of DEHP
      leached during the dialysis session could be easily avoided by careful selection
      of hemodialysis tubing.

PMID- 10089299
TI  - Gastrointestinal transit of pellets in rats: effect of size and density.
AB  - Gastrointestinal distribution kinetics of a large amount (0.5-1 g) of three types
      of non-disintegrating pellets which had the same size (S1, 710-1000 micrometers)
      but different densities (D1, 0.9 and D2, 1.5 g cm-3), or which had the same
      density (D1) but different diameters (S1 and S2, 1250-1600 micrometers) were
      examined in fed rats. The percentage of pellets remaining in the stomach, small
      gut, caecum and colon was measured at suitable intervals. Whatever the size of
      the pellets, the heavier the density, the longer the gastric emptying (2.1 h for
      D2-S1 instead of 1.3 h for D1-S1 and 0.7 h for D1-S2). The small gut transit time
      was not influenced by density but was slightly prolonged by size: 3.3 h for D1-S2
      instead of 2.6 h for D1-S1 and D2-S1. Conversely, the gastrocolonic transit time
      was widely influenced by density (13.5 h for D2-S1) and somewhat by size (8.2 h
      for D1-S2 and 4.5 h for D1-S1). This delays were proportional to caecal residence
      time in the large, sacculated and derivated caecum of rats. In order to use the
      rat as an experimental model for pharmaceutical pellets, those results should
      have implication for the design of dosage forms, particularly those for
      controlled or timed release or those for targeted release at specific positions
      in the gastrointestinal tract.

PMID- 10089300
TI  - Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase
      by molecular replacement.
AB  - Recombinant human glucose 6-phosphate dehydrogenase (G6PD) has been crystallized
      and its structure solved by molecular replacement. Crystals of the natural mutant
      R459L grow under similar conditions in space groups P212121 and C2221 with eight
      or four 515-residue molecules in the asymmetric unit, respectively. A non
      crystallographic 222 tetramer was found in the C2221 crystal form using a 4 A
      resolution data set and a dimer of the large beta + alpha domains of the
      Leuconostoc mesenteroides enzyme as a search model. This tetramer was the only
      successful search model for the P212121 crystal form using data to 3 A. Crystals
      of the deletion mutant DeltaG6PD grow in space group F222 with a monomer in the
      asymmetric unit; 2.5 A resolution data have been collected. Comparison of the
      packing of tetramers in the three space groups suggests that the N-terminal tail
      of the enzyme prevents crystallization with exact 222 molecular symmetry.

PMID- 10089302
TI  - Determination by MAD-DM of the structure of the DNA duplex d[ACGTACG(5-BrU)]2 at
      1.46 A and 100 K.
AB  - A four-wavelength MAD experiment on a new brominated octanucleotide is reported
      here. d[ACGTACG(5-BrU)], C77H81BrN30O32P7, Mr (DNA) = 2235, tetragonal, P43212
      (No. 96), a = 43.597, c = 26.268 A, V = 49927.5 A3, Z = 8, T = 100 K, R = 10.91%
      for 4312 reflections between 15.0 and 1.46 A resolution. The self-complementary
      brominated octanucleotide d[ACGTACG(5-BrU)]2 has been crystallized and data
      measured to 1.45 A at both 293 K and a second crystal flash frozen at 100 K. The
      latter data collection was carried out to the same resolution at the four
      wavelengths 0.9344, 0.9216, 0.9208 and 0.9003 A, around the Br K edge at 0.92 A
      and the structure determined from a map derived from a MAD data analysis using
      pseudo-MIR methodology, as implemented in the program MLPHARE. This is one of the
      first successful MAD phasing experiments carried out at Sincrotrone Elettra in
      Trieste, Italy. The structure was refined using the data measured at 0.9003 A,
      anisotropic temperature factors and the restrained least-squares refinement
      implemented in the program SHELX96, and the helical parameters are compared with
      those previously determined for the isomorphous d(ACGTACGT)2 analogue. The
      asymmetric unit consists of a single strand of octamer with 96 water molecules.
      No countercations were located. The A-DNA helix geometry obtained has been
      analysed using the CURVES program.

PMID- 10089303
TI  - Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A
      resolution.
AB  - The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at
      2.2 A resolution. The cell-cycle arrest agent rapamycin binds FK506-binding
      protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12
      rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is
      responsible for rapamycin's biological activity. The conformation of rapamycin in
      the ternary complex is very similar to that observed in the FKBP12-rapamycin
      binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9
      degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary
      complex. There are extensive rapamycin-protein interactions and relatively few
      interactions between the two protein partners FKBP12 and FRB, these interactions
      mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and
      alpha4 of FRB. The high-resolution refinement has revealed the crucial role of
      several buried waters in the formation of the ternary complex.

PMID- 10089304
TI  - Bound-solvent structures for microgravity-, ground control-, gel- and microbatch
      grown hen egg-white lysozyme crystals at 1.8 A resolution.
AB  - A number of methods can be used to improve the stability of the protein crystal
      growth environment, including growth in microgravity without an air-liquid phase
      boundary, growth in gels and growth under oil ('microbatch'). In this study, X
      ray data has been collected from and structures refined for crystals of hen egg
      white lysozyme (HEWL) grown using four different methods, liquid-liquid dialysis
      on Earth and in microgravity using the European Space Agency's (ESA) Advanced
      Protein Crystallization Facility (APCF) on board the NASA Space Shuttle Life and
      Microgravity Spacelab (LMS) mission (STS-78), crystallization in agarose gel
      using a tube liquid-gel diffusion method and crystallization in microbatch under
      oil. A comparison of the overall quality of the X-ray data, the protein
      structures and especially the bound-water structures has been carried out at 1.8
      A. The lysozyme protein structures corresponding to these four different
      crystallization methods remain similar. A small improvement in the bound-solvent
      structure is seen in lysozyme crystals grown in microgravity by liquid-liquid
      dialysis, which has a more stable fluid physics state in microgravity, and is
      consistent with a better formed protein crystal in microgravity.

PMID- 10089305
TI  - The structures of alpha 2u-globulin and its complex with a hyaline droplet
      inducer.
AB  - Alpha 2u-globulin (A2U) is the major urinary protein excreted by adult male rats.
      The structure of a monoclinic crystal form of A2U was reported in 1992 [Bocskei
      et al. (1992). Nature (London), 360, 186-188]. The structures of an orthorhombic
      crystal form of A2U at 2. 5 A resolution (refined to an R factor of 0.248; Rfree
      = 0.264) and of a complex between A2U and d-limonene 1,2-epoxide (DLO) at 2.9 A
      resolution (R factor = 0.248; Rfree = 0.260) are presented here. DLO is one of a
      diverse group of chemicals which cause a male rat-specific renal carcinogenesis
      called hyaline-droplet nephropathy. The rate-determining step in the development
      of this disorder is the binding of the toxin to A2U. Comparison of the cavities
      in A2U and in the corresponding mouse urinary protein (MUP) reveal that the
      former is tailor-made for small oval hydrophobic ligands such as DLO. The cavity
      in MUP is more shallow and elongated and cannot easily accommodate such ligands.

PMID- 10089306
TI  - Crystallographic analysis of the dsDNA bacteriophage HK97 mature empty capsid.
AB  - HK97 is a member of the Siphovirus family of dsDNA bacteriophages. It is similar
      in architecture to bacteriophage lambda, the type member of this family, with an
      icosahedral capsid of triangulation number T = 7. No high-resolution structural
      information is available for the dsDNA phages, and HK97 is the only dsDNA
      bacteriophage capsid to produce crystals which diffract X-rays. At 650 A in
      diameter, the large size of the particle and resultant large unit cell create
      crystallographic challenges. The empty Head II (mature) particles were expressed
      in Escherichia coli and assembled in vitro, but they have the same morphology as
      the mature HK97 capsid. Previously reported Head II crystals diffracting to 3.5 A
      resolution are examined here in detail. Although the cell dimensions suggest an
      orthorhombic lattice, further analysis demonstrated that the space group was
      monoclinic. This has been confirmed by the present study. Images were recorded on
      the F1 beamline at CHESS and they were processed and scaled, resulting in a data
      set with a cumulative completeness of 65% and a scaling R factor of 7.7% to 7 A.
      The cell dimensions after post-refinement were a = 580, b = 626, c = 788 A, beta
      = 90.0 degrees. From the particle dimensions determined by cryo-electron
      microscopy (cryo-EM), there were determined to be two particles per unit cell.
      Systematic absences of even reflections along the 0k0 lattice line indicate that
      the space group is P21. The rotation function was used to determine the
      orientation of the particles in the unit cell and to confirm the space group. An
      icosahedral twofold axis is approximately, but not exactly, aligned with the
      crystallographic screw (b) axis. An icosahedral twofold axis orthogonal to the
      one approximately parallel to the b axis, is rotated 18 degrees away from the a
      axis. The centers of the two particles must be positioned close to the minimum
      energy packing arrangement for spheres, which places one particle at ((1/4), 0,
      (1/4)) and the other particle at ((3/4), (1/2), (3/4)). The particle position and
      orientation were confirmed by calculating a Patterson function. The particles
      interact closely along icosahedral threefold axes, which occurs both along the
      crystallographic a axis and along the b axis. The particle dimensions derived
      from this packing arrangement agree well with those determined by cryo-EM and
      image reconstruction. The cryo-EM reconstruction will be used as a model to
      initiate phase determination; structure determination at 7 A is under way.

PMID- 10089307
TI  - The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards
      modulation of its selectivity and trimerization.
AB  - The 1.4 A resolution structure of recombinant mouse tumour-necrosis factor alpha
      (mTNF) at 100 K has been determined. The crystals are triclinic, space group P1,
      with unit-cell parameters a = 48.06, b = 48.18, c = 51.01 A, alpha = 114.8, beta
      = 103.6, gamma = 91.1 degrees. The structure was refined to a final
      crystallographic R value of 19.7% (Rfree = 23.3%), including 3477 protein atoms,
      one 2-propanol molecule, one Tris molecule and 240 water molecules. Throughout
      the crystal lattice, the trimers are differently packed compared with human TNF,
      which was crystallized in the tetragonal space group P41212 and refined to 2.6 A
      resolution. The structures of mTNF and human TNF are very similar, diverging
      mainly in regions that are either flexible and/or involved in crystal packing.
      Some loops in mTNF which contain residues important for receptor binding are
      better resolved than in human TNF, such as the surface-exposed loops 30-34 and
      144-147, which are also important for receptor specificity. Compared with human
      TNFs, the channel formed by the three monomers in mTNF is narrower. One 2
      propanol molecule trapped in the trimeric channel could be a lead compound for
      the design of TNF inhibitors.

PMID- 10089308
TI  - Determination of a protein structure by iodination: the structure of iodinated
      acetylxylan esterase.
AB  - Enzymatic and non-enzymatic iodination of the amino acid tyrosine is a well known
      phenomenon. The iodination technique has been widely used for labeling proteins.
      Using high-resolution X-ray crystallographic techniques, the chemical and three
      dimensional structures of iodotyrosines formed by non-enzymatic incorporation of
      I atoms into tyrosine residues of a crystalline protein are described.
      Acetylxylan esterase (AXE II; 207 amino-acid residues) from Penicillium
      purpurogenum has substrate specificities towards acetate esters of D-xylopyranose
      residues in xylan and belongs to a new class of alpha/beta hydrolases. The
      crystals of the enzyme are highly ordered, tightly packed and diffract to better
      than sub-angstrom resolution at 85 K. The iodination technique has been utilized
      to prepare an isomorphous derivative of the AXE II crystal. The structure of the
      enzyme determined at 1.10 A resolution exclusively by normal and anomalous
      scattering from I atoms, along with the structure of the iodinated complex at
      1.80 A resolution, demonstrate the formation of covalent bonds between I atoms
      and C atoms at ortho positions to the hydroxyl groups of two tyrosyl moieties,
      yielding iodotyrosines.

PMID- 10089309
TI  - Structures of thrombin retro-inhibited with SEL2711 and SEL2770 as they relate to
      factor Xa binding.
AB  - Most thrombin active-site inhibitors form a short antiparallel beta-strand with
      residues Ser214-Gly216. However, the Selectide Corp. inhibitors SEL2711 and
      SEL2770 bind to thrombin in a retro fashion, making a parallel beta-strand with
      Ser214-Gly216 similar to other retro-binding inhibitors. The crystallographic
      structures of thrombin-hirugen complexed with SEL2711 and SEL2770, which are
      isostructural with the binary thrombin-hirugen complex, have been determined and
      refined in the 9.0-2.1 A resolution range to final R values of 16.5 and 16.7%,
      respectively. The structures of the SEL2711 and SEL2770 complexes contain 131 and
      104 water molecules, respectively, both of which correspond to occupancies of
      greater than 0.5. The L-4-amidinophenylalanyl residues of SEL2711 and SEL2770 are
      fixed at the S1 specificity site, utilizing favorable ionic and hydrogen-bonding
      interactions between the N atoms of the amidino group and the side-chain O atoms
      of Asp189. The Glu192 residue of thrombin adopts an extended conformation, which
      allows the L-cyclohexylglycyl residue in the P2 retro-binding position of the
      inhibitors to occupy a similar site to the P3 aspartate in thrombin platelet
      receptor peptides bound to thrombin. The N-terminal acetyl group of both
      inhibitors is located in the S2 subsite, while the L-3-pyridyl-(3-methyl)-alanyl
      of SEL2711 and the L-(N,N-dimethyl)lysine of SEL2770 occupy the S3 D-Phe subsite
      of D-PheProArg chloromethyl ketone (PPACK) in the thrombin-PPACK complex. The two
      C-terminal residues of SEL2711 (leucine and proline) point into the solvent and
      have no electron density in the thrombin complex. Those of SEL2770 are also
      positioned into the solvent, but surprisingly produce weak electron density with
      high B values (<B> = 50 A2). Since the Selectide inhibitors are about 10(4) times
      more specific for factor Xa, modeling retro-binding to the latter suggests that
      the selectivity can be a consequence of interactions of the inhibitors in the S3
      S4 binding subsites of factor Xa.

PMID- 10089310
TI  - Structure of basic winged-bean lectin and a comparison with its saccharide-bound
      form.
AB  - The crystal structure of the saccharide-free form of the basic form of winged
      bean agglutinin (WBAI) has been solved by the molecular-replacement method and
      refined at 2.3 A resolution. The final R factor is 19.7% for all data in the
      resolution range 8.0-2.3 A. The asymmetric unit contains two half-dimers, each
      located on a crystallographic twofold axis. The structure of the saccharide-free
      form is compared with that of the complex of WBAI with methyl-alpha-D
      galactoside. The complex is composed of two dimers in the asymmetric unit. The
      intersubunit interactions in the dimer are nearly identical in the two
      structures. The binding site of the saccharide-free structure contains three
      ordered water molecules at positions similar to those of the hydroxyl groups of
      the carbohydrate which are hydrogen bonded to the protein. Superposition of the
      saccharide-binding sites of the two structures shows that the major changes
      involve expulsion of these ordered water molecules and a shift of about 0.6 A of
      the main-chain atoms of the variable loop.

PMID- 10089311
TI  - The high-resolution structure of DNA-binding protein HU from Bacillus
      stearothermophilus.
AB  - Protein HU is a ubiquitous prokaryotic protein which controls the architecture of
      genomic DNA. It binds DNA non-specifically and promotes the bending and
      supercoiling of the double helical structure. HU is involved in many DNA
      associated cellular processes, including replication, transcription and the
      packaging of DNA into chromosome-like structures. Originally determined at medium
      resolution, the crystal structure of HU has now been refined at 2.0 A resolution.
      The high-resolution structure shows that the dimeric molecule is essentially a
      compact platform for two flexible and basic arms which wrap around the DNA
      molecule. To maximize the protein's stability, non-secondary structural regions
      are reduced to a minimum, there is an extensive aromatic hydrophobic core and
      several salt bridges and hydrogen-bonded water molecules knit together crucial
      regions. Based on the original medium-resolution structure of HU, several
      proposals were made concerning the structural basis of HU's ability to bind, bend
      and supercoil DNA. Each of these proposals is fully supported by the high
      resolution structure. Most notably, the surfaces of the molecule which appear to
      mediate protein-DNA and protein-protein interactions have the ideal shapes and
      physicochemical properties to perform these functions.

PMID- 10089312
TI  - Influence of packing interactions on the average conformation of B-DNA in
      crystalline structures.
AB  - The molecular interactions in crystals of oligonucleotides in the B form have
      been analysed and in particular the end-to-end interactions. Phosphate-phosphate
      interactions in dodecamers are also reviewed. A strong influence of packing
      constraints on the average conformation of the double helix is found. There is a
      strong relationship between the space group, the end-to-end interactions and the
      average conformation of DNA. Dodecamers must have a B-form average conformation
      with 10 +/- 0.1 base pairs per turn in order to crystallize in the P212121 and
      related space groups usually found. Decamers show a wider range of conformational
      variation, with 9.7-10. 6 base pairs per turn, depending on the terminal sequence
      and the space group. The influence of the space group in decamers is quite
      striking and remains unexplained. Only small variations are allowed in each case.
      Thus, crystal packing is strongly related to the average DNA conformation in the
      crystals and deviations from the average are rather limited. The constraints
      imposed by the crystal lattice explain why the average twist of the DNA in
      solution (10.6 base pairs per turn) is seldom found in oligonucleotides
      crystallized in the B form.

PMID- 10089313
TI  - Ab initio structure determination of a small protein, rubredoxin, by direct
      methods.
AB  - The direct-methods program SAYTAN has been applied successfully to a known
      protein, rubredoxin, which contains 52 amino-acid residues including an FeS4
      unit, a sulfate ion and 102 solvent water molecules. Starting with initially
      random phases, useful sets can be obtained from multiple trials and selected by
      figures of merit at different resolutions. Phase extension followed by weighted
      Fourier recycling reveals a recognizable structure of rubredoxin. The model is
      refined against 1 A resolution data to an R factor of 14.5% using the program
      SHELXL93.

PMID- 10089314
TI  - Critical initial real-space refinement in the structure determination of arginine
      kinase.
AB  - Arginine kinase (AK), a homologue of creatine kinase, catalyses the reversible
      transfer of a phosphoryl group between a guanidino phosphate and ADP. The family
      of phosphagen kinases eluded structure determination for over 25 years until an
      inactive form creatine kinase (CK) structure was determined [Fritz-Wolf et al.
      (1996). Nature (London), 381, 341-345]. The structure determination of the active
      form transition-state complex was non-trivial, owing to the distant relatedness
      and domain reorientation of AK compared with CK. Phases from a molecular
      replacement solution of the large domain, supplemented by single isomorphous
      replacement and inter-crystal averaging, did not reveal interpretable electron
      density for the small domain. Reciprocal-space refinement of the initial model
      (Rfree = 0.54) by any of the commonly used methods, including post facto
      application of maximum-likelihood methods, led to overfitting without significant
      improvement of the partial initial model. By contrast, in the local real-space
      refinements which proved successful, the interdependence of atoms is limited to
      immediate neighbors, and atomic positions are not influenced by errors or
      omissions in remote parts of the structure. Modest improvement was possible
      without overfitting, and this was critical to the calculation of improved phases.
      Phases were refined and extended from 4.0 to 2.5 A resolution by Fourier
      inversion of omit maps, combination with isomorphous replacement phases and
      averaging between crystal forms, after several batches of real- and reciprocal
      space atomic refinement. The final structure refinement, against a 1.86 A cryo
      data set yielded a high-quality model with R = 0.196 and Rfree = 0.224.

PMID- 10089315
TI  - Combining direct methods with isomorphous replacement or anomalous scattering
      data. VIII. Phasing experimental SIR data with the replacing atoms in a
      centrosymmetric arrangement.
AB  - A multisolution direct method has been proposed to resolve the phase ambiguity
      intrinsic in single isomorphous replacement data of proteins with the replacing
      atoms in a centrosymmetric arrangement. The phase ambiguity of each reflection is
      in fact a 'sign ambiguity' of the phase difference between the phase of the
      native protein and that of the replacing atoms, i.e. +/- |Deltatheta| = theta -
      theta'. The P+ probability formula can be used to derive the signs. The
      multisolution phasing procedure is initiated using random starting values of P+.
      A cluster analysis is used instead of figures of merit to find the correct
      solution. The direct-method phases can be further improved by density
      modification techniques. The method was tested with the experimental SIR data at
      2 A resolution from a known protein aPP; satisfactory results were obtained.

PMID- 10089316
TI  - Automated MAD and MIR structure solution.
AB  - Obtaining an electron-density map from X-ray diffraction data can be difficult
      and time-consuming even after the data have been collected, largely because MIR
      and MAD structure determinations currently require many subjective evaluations of
      the qualities of trial heavy-atom partial structures before a correct heavy-atom
      solution is obtained. A set of criteria for evaluating the quality of heavy-atom
      partial solutions in macromolecular crystallography have been developed. These
      have allowed the conversion of the crystal structure-solution process into an
      optimization problem and have allowed its automation. The SOLVE software has been
      used to solve MAD data sets with as many as 52 selenium sites in the asymmetric
      unit. The automated structure-solution process developed is a major step towards
      the fully automated structure-determination, model-building and refinement
      procedure which is needed for genomic scale structure determinations.

PMID- 10089317
TI  - Crystallization and preliminary X-ray diffraction data of the complex of
      recombinant tick anticoagulant peptide (rTAP) and bovine factor Xa.
AB  - The complex of bovine factor Xa and recombinant tick anticoagulant peptide (rTAP)
      was crystallized in two different crystal forms using polyethylene glycol as a
      precipitant. Form I belongs to space group P42212 with unit-cell dimensions a = b
      = 133.1, c = 68.8 A. It contains one complex per asymmetric unit and diffracts to
      3.0 A resolution. Form II belongs to P41212 (or P43212) with dimensions a = b =
      126.5, c = 146.7 A; it contains two complexes per asymmetric unit and diffracts
      to 2.5 A. The crystals of both forms consist of factor Xa (MW = 45.3 kDa) and
      rTAP (MW = 6.7 kDa).

PMID- 10089318
TI  - Preliminary crystallographic studies on glutamine synthetase from Mycobacterium
      tuberculosis.
AB  - The etiologic agent of tuberculosis, Mycobacterium tuberculosis, has been shown
      to secrete the enzyme glutamine synthetase (TB-GS) which is apparently essential
      for infection. Four crystal forms of a recombinant TB-GS were grown. The one
      chosen for synchrotron X--ray data collection belongs to space group P212121 with
      unit-cell dimensions 208 x 258 x 274 A, yielding 2.4 A resolution data. A
      Matthews number of 2.89 A3 Da-1 is found, corresponding to 24 subunits of
      molecular mass 1300 kDa in the asymmetric unit. From earlier work, the structure
      of Salmonella typhimurium GS, which is 51% identical in sequence to TB-GS, is
      known to be dodecameric with 622 symmetry. Self-rotation calculations on the TB
      GS X-ray data reveal only one set of sixfold and twofold axes of symmetry. A
      Patterson map calculated from the native X-ray data confirms that there are two
      dodecamers in the asymmetric unit, having both their sixfold and twofold axes
      parallel to one another.

PMID- 10089319
TI  - Crystallization and preliminary X-ray analysis of alpha-D-glucuronidase from
      Bacillus stearothermophilus T-6.
AB  - alpha-D-Glucuronidases cleave the alpha-1,2-glycosidic bond of the 4-O-methyl
      alpha-D-glucuronic acid side chain in xylan. Of the xylan-debranching hydrolases,
      these enzymes are the least studied and characterized. The alpha-glucuronidase
      gene (aguA) from Bacillus stearothermophilus T-6 has been cloned, sequenced and
      overproduced in Escherichia coli. The gene encodes for a protein of 679 amino
      acids with a calculated molecular weight of 78480 and a pI of 5.42. alpha
      Glucuronidase T-6 shows high homology to the alpha-glucuronidases of Thermotoga
      maritima (60% identity) and of Tri-choderma reesei (44% identity). Based on the
      amino-acid sequence similarity, it is likely that these enzymes represent a new
      class of glycosyl hydrolases. Crystallographic studies of alpha-glucuronidase T-6
      were initiated to study the mechanism of catalysis, as well as to provide a
      structural basis for rational introduction of enhanced thermostability by site
      specific mutagenesis. In this report, the crystallization and preliminary
      crystallographic characterization of the native alpha-glucuronidase T-6 enzyme is
      described. Two crystal forms were found suitable for detailed crystal structure
      analysis. The T1 form was obtained by the vapour-diffusion method using PEG 4000
      as a precipitant and 2-propanol as an organic additive. The crystals belong to a
      primitive tetragonal crystal system (space group P41212 or P43212) with unit-cell
      dimensions a = b = 76.1 and c = 331.2 A. These crystals are mechanically strong,
      are stable in the X--ray beam and diffract X-rays to better than 2.4 A
      resolution. A full 3.0 A resolution diffraction data set (97.3% completeness,
      Rmerge 9.8%) has recently been collected on one crystal at room temperature using
      a rotating-anode X-ray source and an R-AXIS IIc imaging-plate detector. The M1
      form was obtained and characterized by similar techniques. The best
      crystallization occurred at a slightly lower pH and a lower concentration of 2
      propanol. The crystals belong to a primitive monoclinic crystal system (space
      group P21) with unit-cell dimensions a = 65.8, b = 127.4, c = 96.6 A and beta =
      97.9 degrees. These crystals are also quite strong and stable, and diffract to
      better than 2.8 A resolution. A full 2.8 A resolution diffraction data set (96.2%
      completeness, Rmerge 7.6%) has recently been collected on one crystal at room
      temperature using the same R-AXIS IIc setup. Both forms are currently being used
      to obtain crystallographic phasing via isomorphous heavy-atom derivatives and
      selenomethionine MAD experiments.

PMID- 10089320
TI  - Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo6AATCCGCG)
      containing 2'-deoxy-N6-methoxyadenosine: change in crystal packing with different
      humidity.
AB  - The DNA dodecamer of (CGCGmo6AATCCGCG) containing 2'-deoxy-N6-methoxyadenosine
      has been crystallized for X-ray analysis in order to investigate the effects of
      the modified adenosine on base pairing. It has been found that the crystal
      changes from one form to another during data collection in a manner similar to a
      phase transition. The two crystal structures show that this phenomenon, ascribed
      to differences in humidity, is correlated with a change in the contact angle
      between the two duplexes.

PMID- 10089321
TI  - Crystallization and preliminary x-ray analysis of a nitrate reductase from
      Desulfovibrio desulfuricans ATCC 27774.
AB  - Periplasmic nitrate reductase from the sulfate-reducing bacterium Desulfovibrio
      desulfuricans ATCC 27774 contains two molybdopterin guanine dinucleotide
      cofactors and one [4Fe-4S] cluster as prosthetic groups and catalyzes the
      conversion of nitrate to nitrite. Crystals of the oxidized form of this enzyme
      were obtained using PEG as precipitant and belong to space group P3121 or P3221,
      with unit-cell dimensions a = b = 106.3, c = 135.1 A. There is one monomer of 80
      kDa in the asymmetric unit, which corresponds to a Matthews ratio of 2.75 A3 Da
      1. Using cryo-cooling procedures and X-rays from a rotating-anode generator,
      diffraction was observed to beyond 3.0 A resolution.

PMID- 10089322
TI  - Crystallization and preliminary crystallographic analysis of the major horse
      allergen Equ c 1.
AB  - The secreted protein Equ c 1 is the major component responsible for the induction
      of specific IgE antibodies in patients sensitized to horse allergens. Equ c 1
      belongs to the lipocalin superfamily of hydrophobic ligand-binding proteins,
      which also includes other known allergens. Equilibrium sedimentation and gel
      filtration studies demonstrate that both the glycosylated form of Equ c 1
      purified from horse salivary glands and the non-glycosylated recombinant form
      expressed in bacteria exist predominantly as dimers in solution. As observed for
      other dimeric lipocalins, acidic pH and low protein concentration favour dimer
      dissociation. The recombinant form of Equ c 1 has been crystallized using
      ammonium sulfate as a precipitant. The crystals belong to the tetragonal space
      group P41212 with cell parameters a = b = 84.0, c = 56.1 A, and contain a single
      molecule in the asymmetric unit. A complete data set from native crystals was
      collected at the synchrotron source in Hamburg to 2.9 A resolution using a frozen
      crystal, and structure determination is in progress.

PMID- 10089323
TI  - Crystallization of the haptoglobin-hemoglobin complex.
AB  - Two orthorhombic forms of crystals of the haptoglobin-hemoglobin complex were
      obtained using polyethylene glycol as precipitant. These crystals did not
      diffract well enough for data collection and work on the complex is no longer
      continued. However, the description of the crystallization conditions may be
      useful in future endeavors to obtain suitable crystals.

PMID- 10089324
TI  - Crystallization and preliminary x-ray crystallographic analysis of the B800-820
      light-harvesting complex from Rhodopseudomonas acidophila strain 7050.
AB  - The B800-820 peripheral light-harvesting complex, an integral membrane protein
      from Rhodopseudomonas acidophila strain 7050, has been crystallized in a form
      suitable for X-ray diffraction analysis. The crystals belong to space group R32
      with hexagonal cell dimensions a = 117.20, c = 295.14 A (at 100 K). A complete
      2.8 A resolution data set has been collected and a structure solution obtained
      using molecular-replacement methods.

PMID- 10089325
TI  - Overproduction, purification, crystallization and preliminary x-ray diffraction
      studies of the human spliceosomal protein U5-15kD.
AB  - The gene coding for the human spliceosomal U5 snRNP-specific 15 kDa protein (U5
      15kD) was overexpressed in Escherichia coli, its product purified to homogeneity
      and crystallized. Well diffracting single crystals were obtained by the vapour
      diffusion method in hanging drops and subsequent macroseeding. The crystals
      belong to the orthorhombic space group P21212 with a = 62.3, b = 65.7, c = 37.1
      A. They diffract to at least 3.0 A and contain one molecule in the asymmetric
      unit. A selenomethionine derivative of the protein was prepared and crystallized
      for multiwavelength anomalous diffraction (MAD) data collection.

PMID- 10089326
TI  - Crystallization of the oxygen-evolving reaction centre of photosystem II in nine
      different detergent mixtures.
AB  - Oxygen-evolving photosystem II reaction centres (RCII) isolated from both spinach
      and pea have been crystallized. A single crystal form grew from RCII monomers in
      the presence of nine different three-component mixtures of non-ionic detergents
      and heptane-1,2, 3-triol. The crystals grew as hexagonal rods with dimensions of
      up to 1 x 0.3 x 0.3 mm. The crystals diffracted to a maximum resolution of 6.5 A
      and belong to a hexagonal space group with unit-cell parameters a = 495, b = 495,
      c = 115 A, alpha = beta = 90, gamma = 120 degrees. The growth of a single crystal
      form in the presence of such a large variety of detergents suggests a very
      limited range of crystal lattice formation sites in the RCII complex.

PMID- 10089327
TI  - Crystallization and preliminary x-ray diffraction analysis of the regulatory
      subunit of human protein kinase CK2.
AB  - Protein kinase CK2 is a tetramer composed of two alpha catalytic subunits and two
      beta regulatory subunits. A C-terminal truncated form of the beta subunit has
      been overproduced in Escherichia coli and purified to homogeneity. Two crystal
      forms of the truncated protein which diffract to at least 2 A resolution have
      been obtained. Form I belongs to the monoclinic space group P21, with unit-cell
      parameters a = 49.9, b = 92.9, c = 53.7 A, beta = 96.3 degrees, and yields plate
      like crystals. Form II belongs to the tetragonal space group P42212, with unit
      cell parameters a = 132.19, b = 132.19, c = 63.79 A, and produces rod-shaped
      crystals. Both crystal forms have a functional dimer in the crystal asymmetric
      unit.

PMID- 10089328
TI  - Crystallization and preliminary x-ray analysis of beta-amylase from Bacillus
      polymyxa.
AB  - A truncated beta-amylase (E.C. 3.2.1.2) from Bacillus polymyxa has been
      crystallized using the hanging-drop vapour-diffusion method at 277 K. The
      crystals belong to the orthorhombic space group P212121 with cell dimensions a =
      64.6, b = 141.9, c = 155.1 A and diffract to 2.5 A resolution. The asymmetric
      unit containing three protein molecules was derived from an electron-density map
      calculated at 4 A resolution using MIR phases. This gives a Vm value of 2.36 A3
      Da-1.

PMID- 10089329
TI  - Crystallization and preliminary crystallographic analysis of the hydroxyquinol
      1,2-dioxygenase from Nocardioides simplex 3E: a novel dioxygenase involved in the
      biodegradation of polychlorinated aromatic compounds.
AB  - Hydroxyquinol 1,2-dioxygenase (HQ1,2O) from Nocardioides simplex 3E, an enzyme
      involved in the aerobic biodegradation of a large class of chloroaromatic
      compounds such as 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5
      trichlorophenoxyacetate (2,4,5-T), has been crystallized. HQ1,2O, which
      specifically catalyzes the intradiol cleavage of hydroxyquinol (1,2,4
      trihydroxybenzene), an intermediate in the degradation of a variety of aromatic
      pollutants, to maleylacetate, has been recently purified to homogeneity. The
      enzyme is an homodimer composed of two identical subunits in a alpha 2-type
      quaternary structure, has a molecular weight of about 65 kDa and contains a
      catalytically essential Fe(III) ion. Crystals of HQ1,2O obtained using 2% PEG 400
      and 2 M ammonium sulfate at pH 7.5 as precipitants belong to the orthorhombic
      space group P212121, with unit-cell parameters a = 81.15 (6), b = 86.79 (7), c =
      114.93 (8). Assuming one dimer per asymmetric unit, the Vm value is 2.51 A3 Da-1.
      A complete native data set to 1.8 A resolution has been collected on a laboratory
      source. This is the first intradiol dioxygenase which specifically catalyzes the
      cleavage of hydroxyquinol to give diffraction-quality crystals.

PMID- 10089330
TI  - Crystallization and preliminary x-ray diffraction analysis of hydroxynitrile
      lyase from cassava (Manihot esculenta).
AB  - Hydroxynitrile lyase from M. esculenta (cassava) was crystallized in two
      different crystal forms by the hanging-drop vapour-diffusion method. Crystals of
      form I were obtained from a mixture of polyethylene glycol 8000 and 2-methyl-2,4
      pentanediol, and belong to the tetragonal space group P41212 or its enantiomorph
      P43212, with unit-cell parameters a = b = 105.9, c = 188.9 A and with two
      molecules in the asymmetric unit. These crystals diffract to 2.9 A with
      conventional X-ray sources and beyond 2.1 A resolution with synchrotron
      radiation. The crystals are relatively sensitive to radiation damage and
      conditions for flash-cooling the crystals have been established. A complete
      native data set has been collected up to 2.2 A resolution. Crystal form II has
      been obtained at pH 5.6 using lithium sulfate as a precipitant. The crystals
      apparently belong to the orthorhombic space group P21212, with unit-cell
      parameters a = 117.52, b = 127.09 and c = 78.08 A, have two molecules in the
      asymmetric unit and diffract to beyond 2.0 A resolution. A complete native data
      set has been collected to 2.2 A resolution.

PMID- 10089331
TI  - Crystallization and preliminary x-ray study of two crystal forms of Klebsiella
      oxytoca diol dehydratase-cyanocobalamin complex.
AB  - Two crystal forms of Klebsiella oxytoca diol dehydratase complexed with
      cyanocobalamin have been obtained and preliminary crystallographic experiments
      have been performed. The crystals belong to two different space groups, depending
      on the crystallization conditions. One crystal (form I) belongs to space group
      P212121 with unit-cell parameters a = 76.2, b = 122.3, c = 209. 6 A, and
      diffracts to 2.2 A resolution using an X-ray beam from a synchrotron radiation
      source. The other crystal (form II) belongs to space group P21 with unit-cell
      parameters a = 75.4, b = 132.7, c = 298.8 A, beta = 91.9 degrees, and diffracts
      to 3.0 A resolution. For the purpose of structure determination, a heavy-atom
      derivative search was carried out and some mercuric derivatives were found to be
      promising. Structure analysis by the multiple isomorphous replacement method is
      now under way.

PMID- 10089332
TI  - Crystallization, x-ray diffraction and preliminary structure analysis of
      Mycobacterium tuberculosis chaperonin 10.
AB  - The Mycobacterium tuberculosis chaperonin 10 (Mtcpn10) has been crystallized by
      the sitting-drop vapour-diffusion method. The crystals belong to the monoclinic
      space group P21, with unit-cell parameters a = 76.5, b = 87.9, c = 124.4 A, beta
      = 106.8 degrees. X-ray diffraction data were collected to 2.8 A. The self
      rotation function and the molecular-replacement solution show that the asymmetric
      unit contains a dimer of heptamers related by twofold non-crystallographic
      symmetry. The two heptamers interact through interleaving flexible loops in a
      similar fashion to M. leprae and Gp31 cpn10. In addition to its role in protein
      folding, Mtcpn10 has unique effects on the growth of host cells and is a major
      immunogen in tuberculosis infections. The structure determination will permit the
      analysis of the amino acids identified as important for the protein-folding and
      cell-signalling activity of Mtcpn10.

PMID- 10089333
TI  - Crystallization and preliminary x-ray diffraction studies of a novel bacterial
      esterase.
AB  - A novel bacterial esterase has been crystallized in two forms suitable for X-ray
      diffraction studies. Crystals have been obtained by vapour-phase diffusion at 290
      K using ammonium sulfate as precipitant. The first crystals grew in space group
      C2 with unit-cell parameters a = 134.7, b = 55.8, c = 110.3 A, beta = 125.1
      degrees. A monoclinic data set has been collected to 2.0 A resolution.
      Microseeding yielded a second crystal form which grew in space group P212121 with
      unit-cell parameters a = 57.1, b = 115.4, c = 130.4 A. Native data from these
      crystals have been collected to 1.6 A resolution. A molecular envelope has been
      determined using an uranyl acetate derivative for phase calculation.

PMID- 10089334
TI  - Expression, purification, crystallization and preliminary x-ray analysis of the
      kappa-carrageenase from Pseudoalteromonas carrageenovora.
AB  - A recombinant form of His-tagged kappa-carrageenase from Pseudoalteromonas
      carrageenovora has been expressed, purified and crystallized. Crystals have been
      obtained by the vapour-diffusion method using polyethylene glycol (Mr = 4000) as
      a precipitant. These crystals belong to the space group P212121, with unit-cell
      parameters a = 58.2, b = 62.8, c = 77.9 A, and diffract to 2.2 A resolution on a
      rotating-anode X-ray source.

PMID- 10089335
TI  - Crystallization and preliminary x-ray analysis of the catalytic subunit of the
      ATP-dependent arsenite pump encoded by the Escherichia coli plasmid R773.
AB  - The arsenical resistance (ars) operon of the Escherichia coli plasmid R773
      encodes a system for the active extrusion from cells of the toxic oxyanions
      arsenite (AsIIIO2-) and antimonite (SbIIIO2-) via an ATP-driven pump. The arsA
      and arsB genes of the operon encode the catalytic subunit (ATPase) and the
      membrane subunit of the pump, respectively. The arsC gene codes for a reductase
      that converts arsenate (AsVO43-) to arsenite, thus extending bacterial resistance
      to the pentavalent state of arsenic. Crystals diffracting beyond 2.0 A were
      obtained for the catalytic subunit of the pump (ArsA). These crystals belong to
      space group I222, with unit-cell parameters a approximately 73, b approximately
      76, c approximately 223 A. A single molecule of ArsA, composed of two homologous
      halves, occupies the asymmetric unit of the I222 crystals with a predicted
      solvent content of 46%. Self-rotation function analysis suggests, however, that
      ArsA adopts a molecular packing corresponding to point group 422. One possible
      explanation of this result is that the two homologous halves of ArsA are related
      by a twofold axis of local symmetry and that the two halves of a 'pseudo'
      tetramer are related by a crystallographic twofold axis.

PMID- 10089336
TI  - Purification, crystallization and preliminary x-ray crystallographic analysis of
      a phospholipase A2 from Daboia russelli pulchella.
AB  - Phospholipases are esterolytic enzymes which hydrolyze glycerophospholipids. The
      pharmacological efficiency of phospholipase A2 (PLA2) enzymes is reflected by
      their specificity towards a tissue or organ. The Russell's viper has been
      classified into two classes. Class 1 contains Viper russelli russelli, Viper
      russelli siamensis and Viper russelli formosensis, whereas class 2 contains
      Daboia russelli pulchella. The sequence identity between the PLA2s from these two
      classes is 47%. The novel PLA2 from Daboia russelli pulchella has been
      crystallized using the hanging-drop vapour-diffusion method with ammonium sulfate
      as precipitating agent. Crystals belong to the orthorhombic space group C2221
      with unit-cell parameters a = 77.01, b = 92.29, c = 76.90 A and two molecules in
      the asymmetric unit. These crystals diffract to about 2. 49 A resolution using a
      rotating-anode source.

PMID- 10089337
TI  - Crystallization and preliminary x-ray analysis of glutamate racemase from Aquifex
      pyrophilus, a hyperthermophilic bacterium.
AB  - Glutamate racemase catalyzes the reversible reaction of L-glutamate to D
      glutamate, an essential component of the bacterial cell wall. Glutamate racemase
      from Aquifex pyrophilus has been crystallized by the hanging-drop vapor-diffusion
      method using polyethylene glycol 6000 as a precipitant. The crystals belong to
      space group P6122 or P6522 with unit-cell parameters a = b = 72.1, c = 185.02 A.
      The asymmetric unit contains one molecule, corresponding to a Vm value of 2.35 A3
      Da-1. Complete data sets from a native and a mercury-derivative crystal have been
      collected at 2.0 and 2.3 A resolution, respectively, using a synchrotron
      radiation source.

PMID- 10089338
TI  - Crystallization and preliminary X-ray studies of beta-1, 4-galactanase from
      Aspergillus aculeatus.
AB  - Recombinant beta-1,4-galactanase from Aspergillus aculeatus has been crystallized
      and characterized by X-ray diffraction. Crystals were obtained in hanging drops
      by vapour-diffusion under the conditions 30% PEG 400, 0.2 M CaCl2 and 0.1 M Na
      HEPES buffered to pH 7.5. The crystals diffract to 2.3 A resolution and belong to
      one of the orthorhombic space groups I222 or I212121. The unit-cell dimensions
      are a = 60.42, b = 88.94 and c = 129.08 A. With one molecule in the asymmetric
      unit, the corresponding solvent content is approximately 48%.

PMID- 10089339
TI  - Crystallization and improvement of crystal quality for x-ray diffraction of
      maltooligosyl trehalose synthase by reductive methylation of lysine residues.
AB  - Maltooligosyl trehalose synthase, one of the two enzymes in the coupled trehalose
      biosynthesis system in Sulfolobus acidocaldarius, has been purified and
      crystallized. The chemical modification of this enzyme by reductive methylation
      of lysine residues significantly improved the crystal quality for X-ray
      diffraction experiments. The crystals of the modified enzyme belong to
      orthorhombic space group P212121, with unit-cell parameters a = 56.70, b = 140.1,
      c = 205.2 A measured at cryo-temperature, and are found to contain two enzyme
      molecules per asymmetric unit.

PMID- 10089340
TI  - Structures of orthorhombic lysozyme grown at basic pH and its low-humidity
      variant.
AB  - The structures of orthorhombic lysozyme grown at basic pH and its low-humidity
      variant have been solved and refined at 1.9 and 2.0 A resolution, respectively. A
      comparison of the native structure with those of crystals grown at acidic pH does
      not show any systematic pH-dependent difference in the molecular geometry. The
      conformations, mutual orientation and interactions of the catalytic residues
      Glu35 and Asp52 also remain unchanged. However, comparison between the native and
      low-humidity forms in the orthorhombic form show that the changes in molecular
      geometry which accompany the water-mediated transformation to the low-humidity
      form are more pronounced in the C-terminal residues than in the other regions of
      the molecule. During the transformation from the native to the low-humidity form,
      the locations of only about half the water molecules in the hydration shell
      remain unchanged, but the hydration shell as a whole moves along with the protein
      molecule.

PMID- 10089341
TI  - Further additions to MolScript version 1.4, including reading and contouring of
      electron-density maps.
AB  - MolScript is one of the most popular programs for the generation of publication
      quality figures and the recent re-working of the program should ensure its
      continued popularity. However, some functionality of particular interest to
      crystallographers is not part of the standard program. A modified MolScript
      version 1.4 has been described previously, with more flexible colouring schemes
      among its new features. This report describes further enhancements to MolScript
      version 1.4, including facilities for drawing rods for helices and ribbons for
      oligonucleotides and allowing several formats of electron-density maps to be read
      and contoured using either lines or smoothed triangulated surfaces.

PMID- 10089342
TI  - Software for handling macromolecular envelopes.
AB  - Macromolecular phase-refinement and phase-extension calculations using real-space
      electron-density averaging techniques require accurate envelopes (or masks) to
      define the boundaries of each domain or molecule whose density is to be averaged.
      An extensive set of tools, implemented in four computer programs (O, MAMA, COMA
      and MASKIT) are described which can be used to generate such envelopes (either
      from an atomic model or based on local density-correlation maps), to improve
      them, to remove overlap owing to crystallographic or non-crystallographic
      symmetry, to display them and to manipulate them in a variety of manners.

PMID- 10089343
TI  - Structures of ruthenium-modified Pseudomonas aeruginosa azurin and [Ru(2,2'
      bipyridine)2(imidazole)2]SO4 x 10H2O.
AB  - The crystal structure of Ru(2, 2'-bipyridine)2(imidazole)(His83)azurin (RuAz) has
      been determined to 2.3 A -resolution by X-ray crystallography. The spectroscopic
      and thermodynamic properties of both the native protein and [Ru(2, 2'
      bipyridine)2(imidazole)2]2+ are maintained in the modified protein. Dark-green
      RuAz crystals grown from PEG 4000, LiNO3, CuCl2 and Tris buffer are monoclinic,
      belong to the space group C2 and have cell parameters a = 100.6, b = 35.4, c =
      74.7 A and beta = 106. 5 degrees. In addition, [Ru(2,2'
      bipyridine)2(imidazole)2]SO4 x 10H2O was synthesized, crystallized and
      structurally characterized by X-ray crystallography. Red-brown crystals of this
      complex are monoclinic, space group P21/n, unit-cell parameters a = 13.230 (2), b
      = 18.197 (4), c = 16.126 (4) A, beta = 108.65 (2) degrees. Stereochemical
      parameters for the refinement of Ru(2, 2'-bipyridine)2(imidazole)(His83) were
      taken from the atomic coordinates of [Ru(2,2'-bipyridine)2(imidazole)2]2+. The
      structure of RuAz confirms that His83 is the only site of chemical modification
      and that the native azurin structure is not perturbed significantly by the
      ruthenium label.

PMID- 10089344
TI  - Solution of the structure of the cofactor-binding fragment of CysB: a struggle
      against non-isomorphism.
AB  - The elucidation of the structure of CysB(88-324) by multiple isomorphous
      replacement (MIR) techniques was seriously delayed by problems encountered at
      every stage of the analysis. There was extensive non-isomorphism both between
      different native crystals and between native and heavy-atom-soaked crystals. The
      heavy-atom substitution was invariably weak and different soaking experiments
      frequently led to substitution at common sites. These correlated heavy-atom
      binding sites resulted in an overestimation of the phase information. Missing low
      resolution reflections in the native data set, constituting only 2% of the total
      observations, reduced the power of density modification and phase refinement.
      Finally, the extensive dimer interface made it difficult to isolate a single
      molecule in the course of model building into the MIR maps. The power of maximum
      likelihood refinement (REFMAC) was exploited in solving the structure by means of
      iterative cycles of refinement of a partial model, initially comprising only 30%
      of the protein atoms in the final coordinate set. This technique, which uses
      experimental phases, can automatically discriminate the correct and incorrect
      parts of electron-density maps and give properly weighted combined phases which
      are better than the experimental or calculated ones. This allowed the model to be
      gradually extended by manual building into improved electron-density maps. A
      model generated in this way, containing just 50% of the protein atoms, proved
      good enough to find the transformations needed for multi-crystal averaging
      between different crystal forms. The averaging regime im-proved the phasing
      dramatically such that the complete model could be built. The problems, final
      solutions and some possible causes for the observed lack of isomorphism are
      discussed.

PMID- 10089345
TI  - Refinement and structural analysis of barnase at 1.5 A resolution.
AB  - The structure of Bacillus amyloliquefaciens ribonuclease (barnase), an
      extracellular 110-residue enzyme initially solved at 2.0 A resolution, has been
      refined at 1.5 A using synchrotron radiation and an imaging-plate scanner.
      Refinement with anisotropic atomic displacement parameters resulted in increased
      accuracy of the structure. The final model has a crystallographic R factor of
      11.5% and an Rfree of 17.4%. The three independent molecules in the asymmetric
      unit, referred to as A, B and C, allowed detailed analysis of this final model
      and meaningful comparison with structures of barnase complexed either with
      nucleotide inhibitors or with its natural intracellular inhibitor, barstar. The
      analysis of the overall solvent structure revealed a similar number of water
      molecules associated with each barnase molecule; among these were 16 equivalent
      buried solvent molecules, the locations of which are discussed in detail and
      classified on the basis of their structural role. The importance of the water
      molecules' contribution to the barnase-barstar interaction is also highlighted.
      The high accuracy of the present analysis revealed the presence of a Zn2+ ion
      mediating the contacts between pairs of symmetry-related A, B or C molecules;
      such an ion had previously only been identified for pairs of C molecules.

PMID- 10089346
TI  - Initiating a crystallographic study of UDP-galactopyranose mutase from
      Escherichia coli.
AB  - UDP-galactopyranose mutase, the enzyme responsible for the conversion of UDP
      galactopyranose to UDP-galactofuranose, has been crystallized in a form suitable
      for X-ray diffraction studies. UDP-galactofuranose is a key component of
      mycobacterial cell walls. Crystals of both the native protein and a
      selenomethionine variant have been grown by the vapour-diffusion method in
      hanging drops, and diffract to beyond 3.0 A using synchrotron radiation.
      Equilibration was against a solution of 20%(w/v) polyethylene glycol (4K),
      12%(v/v) 2--propanol, 0.1 M HEPES pH 7.6 at 293.5 K. Crystals grow as thin plates
      of dimensions 0.4 x 0.2 x approximately 0.02 mm. They are monoclinic [corrected],
      space group P21, with unit-cell dimensions a = 71. 12, b = 58.42, c = 96.38 A,
      beta = 96.38 degrees. 92% (native) and 94% (selenomethionine) complete data sets
      have been recorded to 2.9 A (Rmerge = 5.0%) and 3.0 A (Rmerge = 6.9%),
      respectively. The Matthews coefficient is 2.35 A3 Da-1 for a dimer in the
      asymmetric unit, the solvent content being 47%. Diffraction data have also been
      recorded on a putative platinum derivative to 3.5 A.

PMID- 10089347
TI  - Structure of recombinant human lactoferrin expressed in Aspergillus awamori.
AB  - Human lactoferrin (hLf) has considerable potential as a therapeutic agent.
      Overexpression of hLf in the fungus Aspergillus awamori has resulted in the
      availability of very large quantities of this protein. Here, the three
      dimensional structure of the recombinant hLf has been determined by X-ray
      crystallography at a resolution of 2.2 A. The final model, comprising 5339
      protein atoms (residues 1-691, 294 solvent molecules, two Fe3+and two CO32-
      ions), gives an R factor of 0.181 (free R = 0.274) after refinement against 32231
      reflections in the resolution range 10-2.2 A. Superposition of the recombinant
      hLf structure onto the native milk hLf structure shows a very high level of
      correspondence; the main-chain atoms for the entire polypeptide can be
      superimposed with an r.m.s. deviation of only 0.3 A and there are no significant
      differences in side-chain conformations or in the iron-binding sites. Dynamic
      properties, as measured by B-value distributions or iron-release kinetics, also
      agree closely. This shows that the structure of the protein is not affected by
      the mode of expression, the use of strain-improvement procedures or the changes
      in glycosylation due to the fungal system.

PMID- 10089348
TI  - Structure determination of rubredoxin from Desulfovibrio vulgaris Miyazaki F in
      two crystal forms.
AB  - The structures of two crystal forms (form I, P3221, a = b = 43.7, c = 50.7 A;
      form II, P21, a = 27.3, b = 44.9, c = 51.2 A and beta = 90. 6 degrees ) of the
      rubredoxin from Desulfovibrio vulgaris Miyazaki F have been solved by the
      molecular-replacement method. Form I has been refined at a resolution of 2.0 A to
      an R value of 20.8% and includes 32 water molecules. Form II includes 86 water
      molecules and has been refined at 1.9 A resolution to an R value of 17.5%. In
      form II, there are three molecules in the asymmetric unit with the molecules
      related by a non-crystallographic 32 symmetry axis. In both crystal forms, it was
      found that only a few residues effectively participate in the formation of
      intermolecular contacts along both the crystallographic (form I) and the non
      crystallographic (form II) 32 axes. The crystal structure of the form II crystal
      is compared with those of other rubredoxin molecules from anaerobic bacteria.
      From this comparison, a similarity in the core region, which is composed of
      aromatic residues and includes the active centre, has been revealed.

PMID- 10089349
TI  - The structure of plastocyanin from the cyanobacterium Phormidium laminosum.
AB  - The crystal structure of the 'blue' copper protein plastocyanin from the
      cyanobacterium Phormidium laminosum has been solved and refined using 2.8 A X-
      ray data. P. laminosum plastocyanin crystallizes in space group P43212 with unit
      cell dimensions a = 86.57, c = 91.47 A and with three protein molecules per
      asymmetric unit. The final residual R is 19.9%. The structure was solved using
      molecular replacement with a search model based on the crystal structure of a
      close homologue, Anabaena variabilis plastocyanin (66% sequence identity). The
      molecule of P. laminosum plastocyanin has 105 amino-acid residues. The single Cu
      atom is coordinated by the same residues - two histidines, a cysteine and a
      methionine - as in other plastocyanins. In the crystal structure, the three
      molecules of the asymmetric unit are related by a non-crystallographic threefold
      axis. A Zn atom lies between each pair of neighbouring molecules in this
      ensemble, being coordinated by a surface histidine residue of one molecule and by
      two aspartates of the other.

PMID- 10089350
TI  - Stabilization of the i-motif by intramolecular adenine-adenine-thymine base
      triple in the structure of d(ACCCT).
AB  - The crystal structure of d(ACCCT), solved by molecular replacement, shows a four
      stranded i-motif conformation, where two parallel duplexes intercalate with one
      another in opposite orientations. Each duplex is stabilized by hemi-protonated C
      C+ base pairing between parallel strands, and a string of water molecules bridge
      the cytosine N4 atoms to phosphate O atoms. This structure of d(ACCCT) shows
      examples of reversed Hoogsteen and Watson-Crick base pairing in both
      intermolecular and intramolecular manners to stabilize the tetraplex. Noticeably,
      the four-stranded complex is further stabilized at one end by a three-base
      hydrogen-bonding network, in which two adenines and a thymine form four hydrogen
      bonds via a reverse Hoogsteen and an asymmetric adenine-adenine base pairing. The
      structure of d(ACCCT) shows a similar local structure to that found in the d(TAA)
      part of the crystal structure of d(TAACCC) and provides further structural
      evidence that these base arrangements are essential for stabilizing these novel
      DNA super-secondary structures.

PMID- 10089351
TI  - The incorporation of a non-natural amino acid (aza-tryptophan) may help to
      crystallize a protein and to solve its crystal structure. Application to
      bacteriophage lambda lysozyme.
AB  - Until now, wild-type bacteriophage lambda lysozyme had been impossible to
      crystallize. This difficulty could be overcome by the replacement of the four
      tryptophan residues by aza-tryptophans. Analysis of the intermolecular and
      intramolecular contacts in this modification allows understanding of the
      differences in behaviour between the native and modified molecules. Furthermore,
      this mutation was very useful for the creation of new heavy-atom binding sites
      and for the solution of the non-crystallographic symmetry, which is extremely
      important for phase improvement. This procedure seems to be generally applicable,
      at least in the search for new possibilities for heavy-atom binding sites.

PMID- 10089352
TI  - Dimorphism of polyglycine I: structural models for crystal modifications.
AB  - Re-examination of the known data on crystalline forms of polyglycine reveals that
      the crystal modification 'polyglycine I' has two different three-dimensional
      structures depending on the molecular weight. Structural models for both low
      molecular weight (LMW) and high molecular weight (HMW) polyglycine I crystals are
      described. In the LMW crystal model, the molecules have an unusual extended
      conformation generated by alternation of two mirror-symmetrical residual
      conformations along the chain. The molecules are parallel and each chain forms
      interpeptide hydrogen bonds with four adjacent chains. The structural model for
      the HMW crystal represents a composition of twinning crystallites. The
      crystallites themselves consist of antiparallel enantiomorphous chains united by
      hydrogen bonds to form rippled sheets. Calculations of the diffraction patterns
      and packing energy show that these polyglycine I structures have a higher level
      of conformity with the experimental data than previously suggested models. New
      insight into the structure of the polyglycine associates opens up the possibility
      of designing improved silk-like and nylon materials.

PMID- 10089353
TI  - Structures of the catalytic site mutants D99A and H48Q and the calcium-loop
      mutant D49E of phospholipase A2.
AB  - Crystal structures of the active-site mutants D99A and H48Q and the calcium-loop
      mutant D49E of bovine phospholipase A2 have been determined at around 1.9 A
      resolution. The D99A mutant is isomorphous to the orthorhombic recombinant
      enzyme, space group P212121. The H48Q and the calcium-loop mutant D49E are
      isomorphous to the trigonal recombinant enzyme, space group P3121. The two active
      site mutants show no major structural perturbations. The structural water is
      absent in D99A and, therefore, the hydrogen-bonding scheme is changed. In H48Q,
      the catalytic water is present and hydrogen bonded to Gln48 N, but the second
      water found in native His48 is absent. In the calcium-loop mutant D49E, the two
      water molecules forming the pentagonal bipyramid around calcium are absent and
      only one O atom of the Glu49 carboxylate group is coordinated to calcium,
      resulting in only four ligands.

PMID- 10089354
TI  - Isomorphous replacement combined with anomalous dispersion in the linear
      equations: application to a crystal containing four nonapeptide conformers.
AB  - The investigation of the structure of the four conformers of the nonapeptide
      described here has an additional purpose: to illustrate a method for combining
      isomorphous replacement information with anomalous dispersion information within
      the linear equations that have found use in the analysis of multiple-wavelength
      anomalous dispersion data. In the present application, isomorphous replacement
      data were obtained from the replacement of naturally occurring S atoms in the
      nonapeptide with Se atoms. Only one wavelength was used for the analysis: Cu
      Kalpha radiation. Details of the analysis are presented, as well as the
      structural results obtained. It was found that the four independent molecules in
      the structure have similar, but not identical, conformations. The backbones fold
      into predominantly alpha-helices with one or two 310-type hydrogen bonds and have
      extended side chains. Three to four water molecules are associated with each of
      the four head-to-tail regions between the peptides. Optimal packing between
      hydrophobic surfaces may account for the existence of four molecules in an
      asymmetric unit.

PMID- 10089355
TI  - Envelope skeletonization as a means to determine monomer masks and non
      crystallographic symmetry relationships: application in the solution of the
      structure of fibrinogen fragment D.
AB  - An algorithm is described which utilizes the solvent mask generated by the
      solvent-flattening technique to calculate a monomer molecular envelope. In the
      case where non-crystallographic symmetry (NCS) is present in the crystal and self
      rotation angles are known from a self-rotation function, the resultant monomer
      envelopes can be used to search for the translation component of the NCS element
      by a three-dimensional search in real space. In the absence of self-rotation
      angles, the monomer envelope may be used to derive the NCS operators by
      reciprocal-space techniques. Thus, an automatic procedure for averaging directly
      from the solvent-flattening stage can be implemented. The procedure was
      instrumental in the structure solution of fibrinogen fragment D, which is
      presented as an example.

PMID- 10089356
TI  - Real-space molecular-dynamics structure refinement.
AB  - Real-space targets and molecular-dynamics search protocols have been combined to
      improve the convergence of macromolecular atomic refinement. This was
      accomplished by providing a local real-space target function for the molecular
      dynamics program X-PLOR. With poor isomorphous replacement experimental phases,
      molecular dynamics does not improve real-space refinement. However, with high
      quality anomalous diffraction phases convergence is improved at the start of
      refinement, and torsion-angle real-space molecular dynamics performs better than
      other available least-squares or maximum-likelihood methods in real or reciprocal
      space. It is shown that the improvements result from an optimization method that
      can escape local minima and from a reduction of overfitting through the implicit
      use of phases and through use of a local refinement in which errors in remote
      parts of the structure cannot be mutually compensating.

PMID- 10089357
TI  - PBR: a heavy-atom refinement and phasing procedure to reduce phase bias when
      heavy-atom derivatives contain common sites.
AB  - A procedure, called PBR (phase-bias reduction), has been developed to properly
      refine heavy-atom derivatives and to generate less biased heavy-atom phases when
      these derivatives contain common heavy-atom sites. Two independent events are
      obtained by splitting the refinement and phasing calculations into two stages,
      the first in which one of the derivatives having common sites is used together
      with the native amplitudes and the second in which both derivatives with common
      sites are used simultaneously, with one of them being used as the native data
      set. Improved centroid phases and the corresponding figures of merit are obtained
      by phase combination. This procedure has been used in the structure determination
      of the iron-cluster-containing protein -pyruvate-ferredoxin oxidoreductase. When
      the common heavy-atom sites are properly treated by the PBR procedure, the
      resulting calculated centroid phases are improved with respect to classical heavy
      atom refinement centroid phases where all derivatives are refined together. This
      leads to improved electron-density distributions, since anomalous difference
      Fourier maps calculated with the PBR-refined centroid phases and corresponding
      figures of merit show more clearly the positions of the iron sites.

PMID- 10089358
TI  - Reliability of atomic displacement parameters in protein crystal structures.
AB  - Mean standard errors in atomic displacement parameters (ADPs) resulting from
      protein crystal structure determinations are estimated by comparing the ADPs of
      protein-chain pairs of identical sequence within the same crystal or within
      different crystals displaying the same or different space groups. The estimated
      ADP standard errors increase nearly linearly as the resolution decreases - an
      unexpected result given the nonlinear dependence of the resolution on the amount
      of diffraction data. The estimated ADP standard errors are larger for side-chain
      and solvent-exposed atoms than for main-chain and buried atoms and, surprisingly,
      are also larger for residues in the helical secondary structure relative to other
      local backbone conformations. The results allow an estimate of the influence of
      crystallographic refinement restraints on ADP standard errors. Such corrections
      should be applied when comparing different protein structures.

PMID- 10089359
TI  - How many water molecules can be detected by protein crystallography?
AB  - The number of water molecules which are expected to be experimentally located by
      protein crystallography was determined by multiple regression analysis on a test
      set of 873 known protein crystal structures determined at room temperature and on
      another set of 33 structures determined at low temperature. The dependence of the
      number of water molecules included in the protein models as a function of a
      number of significant regressors, such as resolution, fraction of crystal volume
      occupied by the solvent, number of residues in the asymmetric unit, fraction of
      apolar protein surface or secondary structure, has been studied. The number of
      water molecules included in crystallographic models depends primarily on the
      resolution at which the structure has been solved, while the temperature of the
      data collection has only marginal influence. On average, at 2.0 A resolution one
      water molecule per residue is included in the model, while at 1.0 A resolution
      about 1.6-1.7 are crystallographically located. At 2.0 A resolution the well
      known rule-of-thumb of 'one water per protein residue' is confirmed, though the
      number of water molecules experimentally observed is strongly dependent on
      resolution. The results presented are useful in assessing the quality of a
      protein crystal structure, in selecting structural results to be compared and in
      evaluating the expected improvement on the solvent structure when increasing the
      crystallographic resolution.

PMID- 10089360
TI  - Rapid automated molecular replacement by evolutionary search.
AB  - A new procedure for molecular replacement is presented in which an efficient six
      dimensional search is carried out using an evolutionary optimization algorithm.
      In this procedure, a population of initially random molecular-replacement
      solutions is iteratively optimized with respect to the correlation coefficient
      between observed and calculated structure factors. The sensitivity and
      reliability of the method is enhanced by uniform sampling of the rotational
      search space and the use of continuously variable rotational and translational
      parameters. The process is several orders of magnitude faster than a systematic
      six-dimensional search, and comparisons show that it can identify solutions using
      significantly less accurate or less complete search models than is possible with
      two existing molecular-replacement methods. A program incorporating the method,
      EPMR, allows the rapid and highly automated solution of molecular-replacement
      problems involving single or multiple molecules in the asymmetric unit. EPMR has
      been used to solve a number of difficult molecular-replacement problems.

PMID- 10089361
TI  - Optimizing Shake-and-Bake for proteins.
AB  - Shake-and-Bake is a direct-methods procedure which has provided ab initio
      solutions for protein structures containing as many as 1000 independent non-H
      atoms. This algorithm extends the range of conventional direct methods by
      repetitively, unconditionally and automatically alternating reciprocal-space
      phase refinement with filtering in real space to impose constraints. The
      application of SnB to protein-sized molecules is significantly affected by the
      choice made for certain critical parameters, including the number of peaks used
      for density modification, the choice of phase-refinement method and the number of
      refinement cycles. The effects of parameter variation have been studied for six
      protein structures, all of which are solvable by Shake-and-Bake using data at 1.1
      A or higher resolution. Solvability in the resolution range 1.2-1.4 A appears to
      be enhanced by the presence of heavier atoms (S, Cl). Furthermore, it appears
      that in this range the ratio of refinement cycles and triplet phase invariants to
      atoms in the structure must be increased. Large structures lacking atoms of any
      element heavier than oxygen also require non-traditional parameter values.

PMID- 10089362
TI  - Discrimination of solvent from protein regions in native Fouriers as a means of
      evaluating heavy-atom solutions in the MIR and MAD methods.
AB  - An automated examination of the native Fourier is tested as a means of evaluation
      of a heavy-atom solution in MAD and MIR methods for macromolecular
      crystallography. It is found that the presence of distinct regions of high and
      low density variation in electron-density maps is a good indicator of the
      correctness of a heavy-atom solution in the MIR and MAD methods. The method can
      be used to evaluate heavy-atom solutions during MAD and MIR structure solutions
      and to determine the handedness of the structure if anomalous data have been
      measured.

PMID- 10089363
TI  - Conformational attractors on the Ramachandran map.
AB  - Frequency distributions of protein backbone dihedral angles phi and psi have been
      analyzed systematically for their apparent correlation with various
      crystallographic parameters, including the resolution at which the protein
      structures had been determined, the R factor and the free R factor, and the
      results have been displayed in novel differential Ramachandran maps. With
      improved sensitivity compared with conventionally derived heuristic Ramachandran
      maps, such differential maps automatically reveal conformational 'attractors' to
      which phi/psi distributions converge as the crystallographic resolution improves,
      as well as conformations tied specifically to low-resolution structures. In
      particular, backbone angular combinations associated with residues in alpha-
      helical conformation show a pronounced consolidation with substantially narrowed
      phi/psi distributions at higher (better) resolution. Convergence to distinct
      conformational attractors was also observed for all other secondary-structural
      types and random-coil conformations. Similar resolution-dependent phi/psi
      evolutions were obtained for different crystallographic refinement packages,
      documenting the absence of any significant artificial biases in the refinement
      programs investigated here. A comparison of differential Ramachandran maps
      derived for the R factor and the free R factor as independent parameters proved
      the better suitability of the free R factor for structure-quality assessment. The
      resolution-based differential Ramachandran map is available as a reference for
      comparison with actual protein structural data under WebMol, a Java-based
      structure viewing and analysis program (http://www. cmpharm.ucsf.edu/cgi
      bin/webmol.pl).

PMID- 10089364
TI  - Purification, crystallization and preliminary X-ray diffraction data from
      selenomethionine glycinamide ribonucleotide synthetase.
AB  - In this study, the overexpression, purification and crystallization of
      selenomethionine (SeMet) incorporated glycinamide ribonucleotide synthetase (GAR
      syn) from Escherichia coli are reported. The overexpression of SeMet GAR-syn was
      placed under the control of the isopropylthio-beta-galactoside (IPTG) inducible
      T7 RNA-polymerase system. The newly developed construct contained a removable
      histidine tag on the amino terminus of GAR-syn, which allowed rapid purification
      using metal-chelate chromatography techniques. The SeMet GAR-syn crystals were
      grown by hanging-drop vapor diffusion and belong to the space group P212121 with
      unit-cell parameters a = 56.2, b = 62.4 and c = 129.8 A and a single monomer in
      the asymmetric unit. The crystals diffract to 1.6 A resolution and have led to
      the determination of multiple-wavelength anomalous diffraction phases to 2.2 A
      resolution.

PMID- 10089365
TI  - X-ray analysis of crystals of rat phosphatidylinositol-transfer protein with
      bound phosphatidylcholine.
AB  - Phosphatidylinositol-transfer protein (PITP) is a soluble, ubiquitously
      expressed, highly conserved protein encoded by two genes in humans, rodents and
      other mammals. A cDNA encoding the alpha isoform of the rat gene was expressed to
      high levels in Escherichia coli, the protein purified and the homogeneous protein
      used for crystallization studies. Crystals of rat PITP-alpha were obtained by
      vapor-diffusion techniques using the sitting-drop method. Crystals grow within
      two weeks by vapor-diffusion techniques in the presence of polyethylene glycol
      4000. Both crystal forms pack in the monoclinic space group P21. Crystal form I
      has unit-cell parameters a = 44.75, b = 74.25, c = 48.32 A and beta = 114.14
      degrees. Unit-cell parameters for crystal form II are a = 47.86, b = 73.59, c =
      80.49 A and beta = 98.54 degrees. Crystal form I has a Vm of 2.295 A3 Da-1 and an
      estimated solvent content of 46.4% with one molecule per asymmetric unit, while
      crystal form II has a Vm of 2.196 A3 Da-1 and an estimated solvent content of
      44.0%, assuming two molecules per asymmetric unit.

PMID- 10089366
TI  - Crystallization and preliminary X-ray analysis of B-domain fragments of a
      Staphylococcus aureus collagen-binding protein.
AB  - Recombinant proteins of monomeric and dimeric B-domain repeats of a
      Staphylococcus aureus FDA 574 collagen-binding adhesin have been crystallized.
      The single repeat unit (B1) was crystallized in a body-centered orthorhombic
      lattice with a = 96.9, b = 101.3, c = 120. 8 A in either the I222 or I212121
      space group. These crystals diffracted to 2.5 A resolution and the calculated Vm
      values of 3.2 and 2.2 A3 Da-1 suggest the possibility of a dimer or a trimer in
      the asymmetric unit. The two-repeat fragment (B1B2) crystallized in the
      orthorhombic space group P212121 with cell dimensions a = 42.4, b = 79.4, c =
      130.4 A and diffracted to 2.3 A resolution. For this species, the calculated Vm
      value of 2.2 A3 Da-1 indicates the presence of a monomer in the asymmetric unit.

PMID- 10089367
TI  - Crystallization and preliminary X-ray diffraction of Trypanosoma cruzi dUTPase.
AB  - Crystals of Trypanosoma cruzi dUTPase have been grown. Two different morphologies
      are observed, depending on the molecular weight of the PEG used as precipitating
      agent in the mother liquor, both having a hexagonal unit cell with similar
      dimensions. Complete X-ray diffraction data have been collected to low resolution
      for one of the forms. The space group is P6322, with unit-cell dimensions a =
      134.15, c = 147.05 A. Peaks in the self-rotation function and the solvent content
      are consistent with two molecules of dUTPase per asymmetric unit.

PMID- 10089368
TI  - Purification and crystallization of a proteolytic fragment of Escherichia coli
      pyruvate formate-lyase.
AB  - Under anaerobic conditions, the reaction catalysed by pyruvate formate-lyase
      (PFL) is the first reaction after the production of pyruvate in the glycolytic
      pathway. Crystallization trials with Escherichia coli PFL were unsuccessful and
      therefore limited proteolysis was used to produce a stable crystallizable N-
      terminal protein fragment by trypsin cleavage. The molecular weight of this
      cleavage product was found to be 69.6 kDa by MALDI MS analysis, and the DNA
      sequence corresponding to this fragment was cloned. The recombinant protein
      fragment was crystallized by sitting-drop vapour diffusion using polyethylene
      glycol 1000 as precipitant. The crystals, which grew to 2 mm in length and 0.2 mm
      in cross section, belong to the hexagonal space group P61 or P65 with cell
      dimensions a = b = 140.4, c = 215.3 A and two molecules per asymmetric unit. X-
      ray diffraction data were collected from 20 to 3.2 A resolution from a single
      frozen crystal on a synchrotron-radiation beamline.

PMID- 10089369
TI  - Crystallization and preliminary X-ray crystallographic analysis of a vancomycin-N
      acetyl-D-Ala-D-Ala complex.
AB  - A vancomycin-N-acetyl-D-Ala-D-Ala complex has been crystallized by the sitting
      drop vapour-diffusion method using imidazole maleic buffer at pH 7.6. The novel
      crystals obtained belong to the space group P6322 with unit-cell parameters a = b
      = 73.43 (1), c = 277.17 (4) A, gamma = 120 degrees. The crystal density was
      determined as 1. 106 g cm-3 which gives a supercell of 24 molecules (12 dimers)
      per asymmetric unit for an acceptable Matthews number and an estimated solvent
      content of 42%. Data were collected at room temperature to 2. 8 A.

PMID- 10089370
TI  - Crystallization and preliminary X-ray analysis of human thioredoxin peroxidase-B
      from red blood cells.
AB  - Two different crystal forms of human thioredoxin peroxidase-B have been grown by
      vapour diffusion using polyethylene glycol 400 as a precipitant. Monoclinic P21
      crystals were grown from freshly purified protein, whilst orthorhombic P212121
      crystals were grown from purified protein that had been stored in ammonium
      sulfate, but otherwise under the same conditions. The diffraction from both
      crystal forms was observed to extend to beyond 2.0 A resolution using synchrotron
      radiation. Complete native data sets to 1.8 and 3. 7 A have been collected from
      the monoclinic and orthorhombic crystals, respectively.

PMID- 10089371
TI  - Crystallization and preliminary X-ray crystallographic analysis of the
      Pseudomonas aeruginosa cyclohexadienyl dehydratase.
AB  - The title protein has been crystallized in a new crystal form. The crystals
      belong to the cubic space group P4132 (or P4332) with unit-cell dimensions a = b
      = c = 126.1 A at 100 K and typically diffract beyond 1.6 A at the Cornell High
      Energy Synchotron Source (CHESS) A1 beamline.

PMID- 10089372
TI  - Two crystal forms of ModE, the molybdate-dependent transcriptional regulator from
      Escherichia coli.
AB  - The molybdenum-responsive ModE regulatory protein from Escherichia coli has been
      purified and used in crystallization trials. Two crystal forms have been
      observed. Form I is tetragonal, P41212 (or enantiomorph), with a = b = 72.3, c =
      246.2 A and diffracts to medium resolution. Form II is orthorhombic, P21212, with
      a = 82.8, b = 127.9, c = 64.0 A and diffraction has been observed beyond 2.8 A
      resolution. Structural analysis, in combination with ongoing biochemical
      characterization, will assist the elucidation of the structure-activity
      relationship in regulating the uptake of molybdate in bacteria.

PMID- 10089373
TI  - Crystallization and preliminary X-ray analysis of arabinanase A from Pseudomonas
      fluorescens subspecies cellulosa.
AB  - Crystals of 1,5-alpha-arabinanase A from Pseudomonas fluorescens subspecies
      cellulosa have been obtained by vapour diffusion. The crystals belong to the
      space group P6122 with unit-cell parameters a = b = 91.6, c = 179.4 A with one
      molecule in the asymmetric unit. The native crystals and, to a much greater
      extent, heavy-atom soaked crystals are sensitive to radiation which necessitates
      cryocooling. Suitable cryocooling conditions have been established, though a
      shrinkage of the unit cell is observed, with a = b = 88.8 and c = 176.9 A.

PMID- 10089374
TI  - Crystallization and preliminary X-ray diffraction studies of blasticidin S
      deaminase from Aspergillus terreus.
AB  - Blasticidin S deaminase from Aspergillus terreus was crystallized with
      polyethylene glycol 8000. Two types of crystals were grown under the same
      crystallization conditions. One type grew as thin plates, while the other had a
      rhombic shape. The rhombic shaped crystal was suitable for high-resolution
      crystal structure analysis. Precession photographs and diffraction data showed
      that the crystal belonged to orthorhombic space group P212121, with unit-cell
      dimensions a = 70.33, b = 146.56 and c = 56.48 A. The calculated Vm value was
      acceptable when a tetramer of the enzyme was contained in an asymmetric unit.
      Preliminary diffraction data were collected to a resolution of 2.0 A with good
      statistics.

PMID- 10089375
TI  - Crystallization of L-aspartate oxidase, the first enzyme in the bacterial de novo
      biosynthesis of NAD.
AB  - The flavoenzyme L-aspartate oxidase from Escherichia coli was crystallized using
      the hanging-drop vapour-diffusion technique with PEG 4000 as precipitant. The
      crystals belong to space group P3121 (or P3221) with unit-cell parameters a = b =
      84.9, c = 159.9 A. A solvent content of 42% corresponds to a monomer (60 kDa) in
      the asymmetric unit. A complete 2.8 A resolution data set was collected using a
      rotating-anode X-ray generator.

PMID- 10089376
TI  - Crystallization and preliminary X-ray crystallographic analysis of the unusual
      ferritin from Listeria innocua.
AB  - Single crystals of ferritin extracted from Listeria innocua have been obtained by
      the vapour-diffusion method using PEG 1000 as precipitant. The crystals are
      orthorhombic, space group P212121, with unit-cell dimensions a = 87.7, b = 137.5,
      c = 173.1 A. The crystals diffract to 2.9 A resolution on a rotating-anode X-ray
      source and to 2.35 A resolution on a synchrotron X-ray source. The asymmetric
      unit contains one molecule formed by 12 subunits, corresponding to a packing
      density of 2.41 A3 Da-1

PMID- 10089377
TI  - Crystallization of ClfA and ClfB fragments: the fibrinogen-binding surface
      proteins of Staphylococcus aureus.
AB  - Recombinant constructs encoding the fibrinogen-binding domains of ClfA and ClfB
      from Staphylococcus aureus have been crystallized. ClfA was crystallized in the
      orthorhombic space group P212121 with unit-cell parameters a = 39.58, b = 81.39
      and c = 112.65 A. A complete data set was recorded to 2.1 A resolution and had a
      Vm of 2. 3 A3 Da-1 with 46.5% solvent, suggesting one molecule per asymmetric
      unit. Co-crystals of ClfA with the 17 amino-acid C-terminal peptide of fibrinogen
      gamma-chain diffracted to 2.1 A resolution and had unit-cell parameters a =
      39.11, b = 81.39 and c = 109.51 A in the space group P212121. ClfB was
      crystallized in the tetragonal space group P41212 or P43212 with unit-cell
      parameters a = 96.31, b = 96. 31 and c = 84.13 A and diffracted to 2.45 A
      resolution. The estimated Vm of 2.6 A3 Da-1 with 53% solvent indicated one
      molecule in the asymmetric unit.

PMID- 10089378
TI  - Crystallization of hepatitis B virus core protein shells: determination of
      cryoprotectant conditions and preliminary X-ray characterization.
AB  - Hepatitis B virus causes liver cirrhosis and hepatocellular cancer and is a major
      cause of death, particularly in Asia and sub-Saharan Africa. The virus consists
      of an inner core or nucleocapsid, which encloses the viral nucleic acid, with an
      outer lipid envelope containing surface-antigen proteins. The core protein, when
      expressed in E. coli, assembles into spherical shells containing 180 or 240
      subunits, arranged with T = 3 or T = 4 icosahedral symmetry. The C-terminal
      region of the protein is involved in nucleic acid binding, and deletion of this
      region does not prevent capsid formation. C-terminally deleted hepatitis B core
      shells containing 240 subunits have been crystallized and data has been collected
      to 3. 6 A resolution from frozen crystals, using butanediol as a cryoprotectant.
      The crystals have C2 symmetry, with unit-cell parameters a = 538.0, b = 353.0, c
      = 369.6 A, beta = 132.3 degrees.

PMID- 10089379
TI  - Crystallization of importin alpha, the nuclear-import receptor.
AB  - Crystals of recombinant importin alpha, the nuclear-import receptor, have been
      obtained at two different pH conditions by vapour diffusion using sodium citrate
      as precipitant and dithiothreitol as an additive. At pH 4-5, the crystals have
      the symmetry of the trigonal space group P3121 or P3221 (a = b = 78.0, c = 255.8
      A, gamma = 120 degrees ); at pH 6-7, the crystals have the symmetry of the
      orthorhombic space group P212121 (a = 78.5, b = 89.7, c = 100.5 A). In both
      cases, there is probably one molecule of importin alpha in the asymmetric unit.
      At least one of the crystal forms diffracts to a resolution higher than 3 A using
      the laboratory X-ray source; the crystals are suitable for crystal structure
      determination.

PMID- 10089380
TI  - Crystallization and preliminary crystallographic analysis of winged bean acidic
      lectin.
AB  - The acidic lectin (WBAII) from the winged bean (Psophocarpus tetragonolobus)
      binds to the H-antigenic determinant on human erythrocytes and to the T-antigenic
      disaccharide Gal-beta1,3-GalNAc. Two crystal forms of WBAII were obtained in the
      presence of methyl-alpha-D-galactose. Form I belongs to space group R3 with unit
      cell dimensions a = b = 182.11, c = 44.99 A and has one dimer in the asymmetric
      unit. Form II belongs to space group C2 with unit-cell dimensions a = 135.36, b =
      127.25, c = 139.98 A, beta = 95. 9 degrees and has four dimers in the asymmetric
      unit. Intensity data were collected to 3.0 A and to 3.5 A from crystals of form I
      and II, respectively. The structures were solved by the molecular-replacement
      method using the coordinates of the basic form of winged bean lectin.

PMID- 10089381
TI  - Crystallization and preliminary X-ray study of chloroplast glyceraldehyde-3
      phosphate dehydrogenase.
AB  - Glyceraldehyde-3-phosphate dehydrogenase from spinach chloroplasts has been
      crystallized by vapour diffusion in the pH range 7-8.5 in (NH4)2SO4 and Tris-HCl
      buffer or potassium phosphate buffer at room temperature. Crystals of the A4
      isoform, grown at pH 8.5 in Tris-HCl buffer, diffract to 3.0 A (at 100 K) using
      synchrotron radiation. The crystals belong to the orthorhombic C222 space group,
      with unit-cell dimensions a = 145.9, b = 185.9 and c = 106.3 A, and probably
      contain one tetramer per asymmetric unit. Structure determination by molecular
      replacement is in progress.

PMID- 10089382
TI  - Preliminary X-ray analysis of a new crystal form of recombinant pig kidney DOPA
      decarboxylase.
AB  - DOPA decarboxylase is responsible for the synthesis of the key neurotransmitters
      dopamine and serotonin via decarboxylation of L-3, 4-dihydroxyphenylalanine (L
      DOPA) and L-5-hydroxytryptophan, respectively. The crystals of recombinant DOPA
      decarboxylase differ from those previously reported for the enzyme purified from
      pig kidney. They belong to space group P622 with unit-cell dimensions a = b =
      302.6, c = 178.1 A. Both the self-rotation function and the good diffraction
      quality of these crystals (2.5 A on a synchrotron source) suggest that there
      should be at least three protein dimers in the asymmetric unit. Diffraction data
      sets have been collected for the native enzyme and a heavy-atom derivative.

PMID- 10089383
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      recombinant murine Golgi mannosidase IA, a class I alpha-mannosidase involved in
      Asn-linked oligosaccharide maturation.
AB  - Golgi mannosidase IA is a class I alpha-mannosidase which catalyzes the
      conversion of Man9GlcNAc2 or Man8GlcNAc2 oligosaccharide substrates to
      Man5GlcNAc2 during the maturation of Asn-linked oligosaccharides. The enzyme is a
      type II membrane protein, and a recombinant form of mannosidase IA from mouse,
      lacking the transmembrane domain, has been expressed in Pichia pastoris, purified
      to homogeneity and crystallized by the hanging-drop vapor-diffusion method. The
      crystals grow as thin rods, with unit-cell dimensions a = 54.9, b = 135.01, c =
      69.9 A. The crystals exhibit the symmetry of space group P2221 and diffract to
      2.8 A resolution. The asymmetric unit contains one monomer ( approximately 53
      kDa) and has a solvent content of 59%.

PMID- 10089384
TI  - Plasminogen activator inhibitor 1 (PAI-1) in its active conformation:
      crystallization and preliminary X-ray diffraction data.
AB  - Because of its intrinsic lability, wild-type plasminogen activator inhibitor 1
      (PAI-1) cannot be crystallized in its active conformation. Therefore, a stable
      variant of PAI-1 was used to retain the active conformation during
      crystallization. Four different crystallization conditions were evaluated in
      detail and two major types of crystals were detected. Whereas solutions
      consisting of either (i) cacodylate and sodium acetate, (ii) lithium sulfate and
      polyethylene glycol 4K, or (iii) imidazole, sodium chloride and sodium potassium
      phosphate buffer revealed thin platelet crystals, a solution (iv) containing
      ammonium acetate, citrate and polyethylene glycol 4K appeared to enhance the
      formation of clustered brush-like crystals. Crystals grown under condition (iii)
      were found to be suitable for X-ray data collection and consequent structural
      investigation. Data collection was 79.8% complete with a maximum resolution of
      2.92 A. Importantly, PAI-1 retained its functional properties under all
      conditions.

PMID- 10089385
TI  - Crystal-growth kinetics of protein single crystals along capillary tubes in the
      gel-acupuncture technique.
AB  - In attempts to obtain protein crystals of a sufficient size for structural
      studies, lack of knowledge of the physicochemical properties of protein solutions
      and of their crystal-growth behaviour lead to a bottleneck for drug design as
      well as for X-ray crystallography. Most formal investigations on crystal-growth
      phenomena have been focused on equilibrium studies, where the protein is soluble,
      and on the kinetics of crystal growth, which is related to both nucleation and
      crystal-growth phenomena. The aim of this work is to measure the crystal-growth
      rate along a capillary tube used as a growing cell. These experiments were
      carried out using the gel-acupuncture technique [Garcia-Ruiz et al. (1993).
      Mater. Res. Bull. 28, 541-546; Garcia-Ruiz & Moreno (1994). Acta Cryst. D50, 484
      490; Garcia-Ruiz & Moreno (1997). J. Cryst. Growth, 178, 393-401]. Crystal-growth
      investigations took place using lysozyme and thaumatin I as standard proteins.
      The maximum average growth rate obtained in the lower part of the capillary tube
      was about 35 A s-1 and the minimum average growing rate in the upper part of the
      capillary tube was about 8 A s-1. The crystal-growth rate as a function of the
      supersaturation was experimentally estimated at a constant height along the
      capillary tube.

PMID- 10089386
TI  - Faster publication in acta crystallographica section D 

PMID- 10089387
TI  - Deposition and release of macromolecular structural data.

PMID- 10089388
TI  - Deposition of structure factors at the Protein Data Bank.

PMID- 10089389
TI  - Improving the diffraction quality of MTCP-1 crystals by post-crystallization
      soaking.
AB  - Significant improvement in the resolution and quality of the X-ray diffraction of
      crystals of MTCP-1 protein was observed on post-crystallization soaking. The MTCP
      1 crystals grown from 1.5 M ammonium sulfate diffracted to only 3.0 A resolution
      with some disorder in the diffraction. After post-crystallization soaking in a
      solution containing 2.0 M ammonium sulfate, the disorder was eliminated and
      diffraction extended to better than 2.0 A resolution. Both native and
      selenomethionine-enriched crystals demonstrated better diffraction after soaking
      for several months. This simple technique may be useful to improve the
      diffraction quality of protein crystals generally.

PMID- 10089390
TI  - The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution.
AB  - Carbamoyl phosphate synthetase catalyzes the formation of carbamoyl phosphate
      from one molecule of bicarbonate, two molecules of Mg2+ATP and one molecule of
      glutamine or ammonia depending upon the particular form of the enzyme under
      investigation. As isolated from Escherichia coli, the enzyme is an alpha,beta
      heterodimer consisting of a small subunit that hydrolyzes glutamine and a large
      subunit that catalyzes the two required phosphorylation events. Here the three
      dimensional structure of carbamoyl phosphate synthetase from E. coli refined to
      2.1 A resolution with an R factor of 17.9% is described. The small subunit is
      distinctly bilobal with a catalytic triad (Cys269, His353 and Glu355) situated
      between the two structural domains. As observed in those enzymes belonging to the
      alpha/beta-hydrolase family, the active-site nucleophile, Cys269, is perched at
      the top of a tight turn. The large subunit consists of four structural units: the
      carboxyphosphate synthetic component, the oligomerization domain, the carbamoyl
      phosphate synthetic component and the allosteric domain. Both the
      carboxyphosphate and carbamoyl phosphate synthetic components bind Mn2+ADP. In
      the carboxyphosphate synthetic component, the two observed Mn2+ ions are both
      octahedrally coordinated by oxygen-containing ligands and are bridged by the
      carboxylate side chain of Glu299. Glu215 plays a key allosteric role by
      coordinating to the physiologically important potassium ion and hydrogen bonding
      to the ribose hydroxyl groups of ADP. In the carbamoyl phosphate synthetic
      component, the single observed Mn2+ ion is also octahedrally coordinated by
      oxygen-containing ligands and Glu761 plays a similar role to that of Glu215. The
      carboxyphosphate and carbamoyl phosphate synthetic components, while
      topologically equivalent, are structurally different, as would be expected in
      light of their separate biochemical functions.

PMID- 10089391
TI  - Structure of the bifunctional inhibitor of trypsin and alpha-amylase from ragi
      seeds at 2.9 A resolution.
AB  - The crystal structure of a bifunctional inhibitor of alpha-amylase and trypsin
      from the seeds of ragi (Indian finger millet, Eleusine coracana Gaertneri) has
      been determined by an X-ray diffraction method. The inhibitor consists of 122
      amino acids with five disulfide bridges and belongs to the plant alpha
      amylase/trypsin-inhibitor family. This is the first crystal structure
      determination of a member of this family. The protein, purified from the seeds of
      ragi, has a molecular mass of 13300 Da with a pI of 10.3. Crystals were grown by
      a microdialysis method using ammonium sulfate as precipitant. The improved
      purification protocol and the modified crystallization conditions enabled
      reproducible growth of the crystals. The cell parameters are a = 41. 2, b = 47.4,
      c = 55.9 A. The intensity data were collected to 2.9 A resolution, and the
      crystal structure was determined using the molecular-replacement method. The
      structure was refined using the X-PLOR and CCP4 program packages to a
      conventional R factor of 21%. The structure contains four alpha-helices between
      residues 19-29, 37-51, 56-65 and 90-95, and two short antiparallel beta-strands
      between residues 67-70 and 73-75.

PMID- 10089392
TI  - Structure analysis of bovine heart cytochrome c oxidase at 2.8 A resolution.
AB  - The crystal structure of bovine heart cytochrome c oxidase has been determined at
      2.8 A resolution by the multiple isomorphous replacement (MIR) method with three
      heavy-atom derivatives. An asymmetric unit of the crystal has a molecular weight
      of 422 kDa. Eight heavy atoms as main sites of a CH3HgCl derivative were clearly
      located by solving the difference Patterson function. The electron density
      obtained by the MIR method was refined by density modification, consisting of
      solvent flattening, histogram matching and non-crystallographic symmetry
      averaging. The enzyme exhibits a dimeric structure in the crystal. Out of 3606
      amino-acid residues in 26 subunits in the dimer, 3560 residues were located in
      the electron-density map. The structure was refined by X-PLOR. The final R factor
      and the free R factor were 0.199 and 0.252 at 2.8 A resolution, respectively. One
      monomer in the dimeric structure with a stronger packing interaction has a lower
      averaged temperature factor than the other, by 16 A2. The region +/-12 A from the
      centre of the transmembrane part is almost 100% alpha-helix, despite the glycine
      residue content being as high as 7.1% in the transmembrane region. The residues
      around haem a of animals have evolved away from those of bacteria in contrast
      with the residues of the haem a3. The hierarchy of the structural organization of
      the enzyme complex has been proposed on the basis of intersubunit interactions.

PMID- 10089393
TI  - High-resolution refinement of orthorhombic bovine pancreatic phospholipase A2.
AB  - The X-ray structure of recombinant bovine pancreatic phospholipase A2 (PLA2),
      which specifically catalyzes the cleavage of the sn-2 acylester bond of
      phospholipids, has been refined at 1.5 A resolution. The crystal belongs to the
      space group P212121 with unit-cell parameters a = 47.12, b = 64.59 and c = 38.14
      A similar to the native enzyme reported previously by Dijkstra et al. [J. Mol.
      Biol. (1981), 147, 97-123]. The refinement converged to an R value of 18.4%
      (Rfree = 22.8%) for 16 374 reflections between 10.0 and 1.5 A resolution. The
      surface-loop residues (60-70) are ordered in the present orthorhombic recombinant
      enzyme, but disordered in the trigonal recombinant enzyme. The active-site
      residues, His48, Asp99, and the catalytic water superimpose well with the
      trigonal form. Besides the catalytic water which is hydrogen bonded to His48, it
      is often seen that there is a second water attached to the same N atom of His48
      and simultaneously hydrogen bonded to the O atom of Asp49. It is thought that the
      second water facilitates the tautomerism of His48 for enzyme catalysis. The
      catalytic water is also hydrogen bonded to the equatorial water coordinated to
      the calcium ion. In addition to the equatorial water, there is also an axial
      calcium water and the additional structural water. These five common water
      molecules are hydrogen bonded to the additional 16 water molecules in the present
      orthorhombic structure which may further enhance the structural integrity of the
      active site. Besides the protein and one calcium ion, a total of 134 water
      molecules were located in the present high-resolution refinement.

PMID- 10089394
TI  - Neutron Laue diffraction studies of coenzyme cob(II)alamin.
AB  - Using a recently designed neutron single-crystal diffractometer utilizing a
      narrow-band Laue concept (LADI), diffraction data were collected from a crystal
      of the coenzyme cob(II)alamin (B12r), crystallized from a mixture of D2O and
      perdeuterated acetone. The instrument was placed at the end of a cold neutron
      guide at the Institute Laue Langevin (ILL, Grenoble, France), and data collection
      with neutrons of 1.8-8.0 A wavelength to a crystallographic resolution of 1.43 A
      was complete after about 36 h. This compares favourably with a previous
      experiment utilizing the same crystal specimen, where more than four weeks were
      required to collect monochromatic diffraction data to about 1 A resolution. Using
      the Laue data, the structure was solved by molecular replacement with the known X
      ray crystal structure. Difference density maps revealed the atomic positions
      (including deuterium atoms) of seven ordered solvent water molecules and two
      (partially disordered) acetone molecules. These density maps were compared with
      corresponding maps computed with monochromatic neutron-diffraction data collected
      to 1. 0 A resolution using the same crystal specimen, as well as to maps derived
      from high-resolution (0.90 A) synchrotron X-ray data. In spite of the better
      definition of atomic positions in the two high-resolution maps, the 1.43 A LADI
      maps show considerable power for the determination of the location of hydrogen
      and deuterium positions.

PMID- 10089395
TI  - Structural studies on the binding of 4-methylumbelliferone glycosides of chitin
      to rainbow trout lysozyme.
AB  - Two complexes between rainbow trout lysozyme (RBTL) and 4-methylumbelliferyl
      chitobioside, 4MeU-(GlcNAc)2, and chitotrioside, 4MeU-(GlcNAc)3, were produced by
      co-crystallization and soaking, respectively, and the crystal structures were
      solved at 2.0 A resolution. The results show that 4-MeU-(GlcNAc)3 binds in
      subsites A-D and that 4-MeU-(GlcNAc)2 binds in subsites B-D in the active-site
      cleft of RBTL. This agrees well with earlier crystallographic studies on the
      binding of oligosaccharides of chitin to RBTL, which showed that (GlcNAc)3 binds
      to sites B-D in RBTL and not to A-C as seen in the human and turkey egg-white
      lysozymes. For both complexes the 4-MeU moiety in site D has diffuse electron
      density and is flexible, as it is only bound to water molecules and not to the
      protein. Since no electron density was observed in site E, the solved structures
      give views of nonproductive enzyme-substrate complexes.

PMID- 10089396
TI  - A MAD experiment performed at the white line of the iridium LIII absorption edge
      in lysozyme.
AB  - A multiple-wavelength anomalous diffraction (MAD) experiment was performed on an
      iridium derivative of hen egg-white lysozyme. Diffraction data were measured at
      five wavelengths on the X31 EMBL beamline on the DORIS III storage ring and at
      two further wavelengths on the X11 beamline. Four iridium-binding sites were
      located from the dispersive anomalous differences between two wavelengths at the
      rising and falling inflection points of the Ir LIII-edge white line using direct
      methods. All other attempts to determine the heavy-atom positions failed. The
      results demonstrate an experimental method whereby systematic error in MAD data
      due to sample absorption can be reduced where a white line is present in the
      absorption spectrum of a heavy atom.

PMID- 10089397
TI  - A low-resolution structure of rice dwarf virus determined by ab initio phasing.
AB  - Rice dwarf virus crystals belong to space group I222 with cell parameters a = 770
      (2), b = 795 (5), c = 814 (5) A and alpha = beta = gamma = 90 degrees. The unit
      cell of the crystal contains two viruses at the origin and body-centred
      positions. Using data synthesized from a rice dwarf virus model crystal in the
      space group I222, the possibility of ab initio phasing was thoroughly examined.
      The centric nature of the initial phases was unexpectedly broken by extensive
      iteration of the non-crystallographic symmetry averaging. The structure of rice
      dwarf virus was then solved with ab initio phasing up to 20 A resolution. The
      triangulation number determined by the present study is T = 13, which is
      different from the triangulation number, T = 9, previously determined by electron
      microscopy [Uyeda & Shikata (1982). Ann. Phytopathol. Soc. Jpn, 48, 295-300].

PMID- 10089398
TI  - Structures of the HIV-1 capsid protein dimerization domain at 2.6 A resolution.
AB  - The human immunodeficiency virus type I (HIV-1) capsid protein is initially
      synthesized as the central domain of the Gag polyprotein, and is subsequently
      proteolytically processed into a discrete 231-amino-acid protein that forms the
      distinctive conical core of the mature virus. The crystal structures of two
      proteins that span the C-terminal domain of the capsid are reported here: one
      encompassing residues 146-231 (CA146-231) and the other extending to include the
      14-residue p2 domain of Gag (CA146-p2). The isomorphous CA146-231 and CA146-p2
      structures were determined by molecular replacement and have been refined at 2.6
      A resolution to R factors of 22.3 and 20.7% (Rfree = 28.1 and 27.5%),
      respectively. The ordered domains comprise residues 148-219 for CA146-231 and 148
      218 for CA146-p2, and their refined structures are essentially identical. The
      proteins are composed of a 310 helix followed by an extended strand and four
      alpha-helices. A crystallographic twofold generates a dimer that is stabilized by
      parallel packing of an alpha-helix 2 across the dimer interface and by packing of
      the 310 helix into a groove created by alpha-helices 2 and 3 of the partner
      molecule. CA146-231 and CA146-p2 dimerize with the full affinity of the intact
      capsid protein, and their structures therefore reveal the essential dimer
      interface of the HIV-1 capsid.

PMID- 10089399
TI  - Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution.
AB  - The three-dimensional structure of the R form of rabbit liver fructose 1,6
      bisphosphatase (Fru-1,6-Pase; E.C. 3.1.3.11) has been determined by a combination
      of heavy-atom and molecular-replacement methods. A model, which includes 2394
      protein atoms and 86 water molecules, has been refined at 2.3 A resolution to a
      crystallographic R factor of 0.177. The root-mean-square deviations of bond
      distances and angles from standard geometry are 0.012 A and 1.7 degrees,
      respectively. This structural result, in conjunction with recently redetermined
      amino-acid sequence data, unequivocally establishes that the rabbit liver enzyme
      is not an aberrant bisphosphatase as once believed, but is indeed homologous to
      other Fru-1,6-Pases. The root-mean-square deviation of the Calpha atoms in the
      rabbit liver structure from the homologous atoms in the pig kidney structure
      complexed with the product, fructose 6-phosphate, is 0.7 A. Fru-1,6-Pases are
      homotetramers, and the rabbit liver protein crystallizes in space group I222 with
      one monomer in the asymmetric unit. The structure contains a single endogenous
      Mg2+ ion coordinated by Glu97, Asp118, Asp121 and Glu280 at the site designated
      metal site 1 in pig kidney Fru-1,6-Pase R-form complexes. In addition, two
      sulfate ions, which are found at the positions normally occupied by the 6
      phosphate group of the substrate, as well as the phosphate of the allosteric
      inhibitor AMP appear to provide stability. Met177, which has hydrophobic contacts
      with the adenine moiety of AMP in pig kidney T-form complexes, is replaced by
      glycine. Binding of a non-hydrolyzable substrate analog, beta-methyl-fructose 1,6
      bisphosphate, at the catalytic site is also examined.

PMID- 10089400
TI  - The decameric structure of bovine pancreatic trypsin inhibitor (BPTI)
      crystallized from thiocyanate at 2.7 A resolution.
AB  - The structure of a monoclinic form of bovine pancreatic trypsin inhibitor (BPTI)
      crystallized from a thiocyanate solution has been determined and refined at 2.7 A
      resolution. The space group is P21 with a = 71.56, b = 73.83, c = 64.47 A, beta =
      93.9 degrees and Z = 20. The ten independent molecules were located by a multi
      body molecular-replacement search as developed in the AMoRe program, starting
      from a single monomer model (PDB code: 6PTI). The molecular arrangement of the
      subunits is a decamer resulting from the combination of two orthogonal fivefold
      and twofold non-crystallographic axes. This builds a globular micelle-like
      particle which minimizes hydrophobic interactions with the solvent. The
      refinement was conducted with non-crystallographic symmetry constraints up to a
      final residual of R = 0.20 (Rfree= 0.26). The root-mean-square deviations from
      ideal geometry were 0.015 A and 1.6 degrees on bond distances and bond angles,
      respectively. Several sites for thiocyanate ions were analyzed.

PMID- 10089401
TI  - Refined structure of orthorhombic lysozyme crystallized at high temperature:
      correlation between morphology and intermolecular contacts.
AB  - The structure of orthorhombic hen egg-white lysozyme (HEWL) crystallized at 310 K
      has been refined at 1.7 A resolution. Large displacements of the side-chain atoms
      with respect to the tetragonal structure were observed in many places, in
      contrast to small displacements of the main-chain atoms. A chloride-ion binding
      site was observed at an interface of two molecules, but at a different position
      to the binding site in the tetragonal form. The analysis of intermolecular
      contacts in the crystal has shown the presence of three independent
      intermolecular contacts which are called macrobonds A, B and C. Arginine side
      chains are frequently involved in these macrobonds, suggesting that the high
      frequency of this residue in HEWL may be a possible reason for the multiple
      polymorphs of this protein. The crystal forms were determined using a light
      reflecting device on a four-circle diffractometer. Correlations between crystal
      forms and the three-dimensional macrobond networks were interpreted in terms of
      their components in various crystallographic planes, making use of approximate
      strengths of hydrogen-bond and van der Waals interatomic forces.

PMID- 10089402
TI  - Structure of a monoclonal 2E8 Fab antibody fragment specific for the low-density
      lipoprotein-receptor binding region of apolipoprotein E refined at 1.9 A.
AB  - The crystal structure of the Fab fragment of 2E8, the monoclonal IgG1,kappa
      antibody specific for the low-density lipoprotein (LDL) receptor-binding region
      of apolipoprotein E (apoE), has been solved by molecular replacement and refined
      at 1.9 A resolution (PDB entry 12E8). Two 2E8 Fab molecules in the asymmetric
      unit are related by noncrystallographic symmetry and are hydrogen bonded through
      a beta-sheet-like intermolecular contact between the heavy-chain complementarity
      determining regions 3 (CDRH3) of each molecule. The structure has been refined to
      an R value of 0.22 (Rfree = 0.27). The initially ill-defined heavy-chain constant
      domain (CH1) of 2E8 has been retraced with the aid of automatic refinement,
      confirming the beta-sheet tracing independently of any starting models. As a
      resolution better than 2 A is not common for Fab fragments, this model represents
      a well defined Fab structure and should prove useful in MR solution of other Fab
      fragments. Furthermore, in the absence of an LDL-receptor structure, the homology
      of the 2E8 CDRH2 to the ligand-binding domain of the LDL receptor has been
      exploited to model the apoE-LDL-receptor interaction.

PMID- 10089403
TI  - On the molecular-replacement problem in the presence of merohedral twinning:
      structure of the N-terminal half-molecule of human lactoferrin.
AB  - The structure of a hemihedrally twinned protein crystal with two molecules in the
      asymmetric unit was solved by molecular replacement. The protein, a site-specific
      mutant of the N-terminal half-molecule of human lactoferrin, is able to undergo
      an internal rigid-body domain motion. Therefore, determining the structure
      required the independent positioning of four protein domains. The molecular
      replacement solutions were obtained using a conventional real-space rotation
      function, and a translation function based on the linear correlation coefficient.
      Once the molecules were positioned, it was necessary to assign them to the
      appropriate twin domain. Several methods for doing this are described, one of
      which leads to a determination of the volume of each twin domain. In the appendix
      to the paper we discuss the interpretation of the self-rotation function in the
      presence of merohedral twinning.

PMID- 10089404
TI  - High-resolution structures of three new trypsin-squash-inhibitor complexes: a
      detailed comparison with other trypsins and their complexes.
AB  - An anionic trypsin from Atlantic salmon and bovine trypsin have been complexed
      with the squash-seed inhibitors, CMTI-I (Cucurbita maxima trypsin inhibitor I, P1
      Arg) and CPTI-II (Cucurbita pepo trypsin inhibitor II, P1 Lys). The crystal
      structures of three such complexes have been determined to 1.5-1.8 A resolution
      and refined to crystallographic R factors ranging from 17.6 to 19.3%. The two
      anionic salmon-trypsin complexes (ST-CPTI and ST-CMTI) and the bovine-trypsin
      complex (BT-CPTI) have been compared to other trypsin-inhibitor complexes by
      means of general structure and primary and secondary binding features. In all
      three new structures, the primary binding residue of the inhibitor binds to
      trypsin in the classical manner, but with small differences in the primary and
      secondary binding patterns. Lysine in CPTI-II binds deeper in the specificity
      pocket of bovine trypsin than lysine in other known lysine-bovine-trypsin
      complexes, and anionic salmon trypsin lacks some of the secondary binding
      interactions found in the complexes formed between squash inhibitors and bovine
      trypsin. The ST-CMTI complex was formed from the reactive-site-cleaved form of
      the inhibitor. However, well defined electron density was observed for the P1-P1'
      peptide bond, together with a hydrogen-bonding pattern virtually identical to
      those of all serine-protease-protein-inhibitor complexes, indicating a
      resynthesis of the scissile bond.

PMID- 10089405
TI  - Crystallogenesis studies on yeast aspartyl-tRNA synthetase: use of phase diagram
      to improve crystal quality.
AB  - Aspartyl-tRNA synthetase (AspRS) extracted from yeast is heterogeneous owing to
      proteolysis of its positively charged N-terminus; its crystals are of poor
      quality. To overcome this drawback, a rational strategy was developed to grow
      crystals of sufficient quality for structure determination. The strategy is based
      on improvement of the protein homogeneity and optimization of crystallization,
      taking advantage of predictions from crystal-growth theories. An active mutant
      lacking the first 70 residues was produced and initial crystallization conditions
      searched. The shape and habit of initial crystals were improved by establishing a
      phase diagram of protein versus crystallizing-agent concentrations. Growth of
      large well faceted crystals takes place at low supersaturations near the
      isochronic supersolubility curve. Further refinement led to reproducible growth
      of two crystalline forms of bipyramidal (I) or prismatic (II) habit. Both
      diffract X-rays better than crystals previously obtained with native AspRS.
      Complete data sets were collected at 3 A resolution for form I (space group
      P41212) and form II (space group P3221) and molecular-replacement solutions were
      found in both space groups.

PMID- 10089406
TI  - Multiwavelength anomalous solvent contrast (MASC): derivation of envelope
      structure-factor amplitudes and comparison with model values.
AB  - A previous article [Fourme et al. (1995). J. Synchrotron Rad. 2, 36-48] presented
      the theoretical foundations of MASC, a new contrast-variation method using
      multiwavelength anomalous scattering, and reported the first experimental
      results. New experiments have been conducted both at the ESRF (Grenoble, France)
      and at LURE-DCI (Orsay, France), using cryocooled crystals of three proteins of
      known structures and very different molecular weights. Amplitudes of {GammaT(h)},
      the 'normal' structure factors of the anomalously scattering part of the crystal
      including the solvent zone and the ordered anomalous scattering sites (if any),
      have been extracted from multiwavelength data. In the very low resolution range
      (d >/= 20 A), the agreement between experimental {GammaT(h)} and model values
      calculated from the bulk solvent is all the more satisfactory since the molecular
      weight of the protein is high. For spacings between 10 and 20 A, the agreement
      between experimental {GammaT(h)} and model values is also satisfactory if one
      takes into account ordered anomalous scatterer sites. Such sites have been found
      in the three cases.

PMID- 10089407
TI  - On the application of phase relationships to complex structures. XXXVI: some
      experiments with a small protein without heavy atoms.
AB  - The direct-methods program MULTAN88 has been applied to a known protein,
      ribonuclease (RNAP1), containing 808 non-H atoms, including five S atoms, plus 83
      ordered solvent water molecules. Phase sets with mean phase errors between 69 and
      75 degrees were selected by modified figures of merit for trials with the full
      data at 1.17 A resolution and also with restricted data at 1.25 and 1.5 A
      resolution. These figures of merit had previously only been applied to protein
      structures containing heavy atoms, and this is the first demonstration of their
      usefulness with no heavy atom present. An initial set of 1091 phases from a 1.17
      A trial was developed by an objective procedure to give the full structure with a
      residual of 0. 21, which agrees well with the published structure.

PMID- 10089408
TI  - On the correlation between the main-chain and side-chain atomic displacement
      parameters (B values) in high-resolution protein structures.
AB  - Correlation coefficients (CCs) between the mean atomic displacement parameters (B
      values) of the main-chain and the side-chain atoms in selected high-resolution
      protein structures are distributed over a broad range (0.5-1.0). The distribution
      of CCs is found to be related to the mean difference in B values of Calpha and
      Cbeta atoms. High CCs are also associated with the frequent occurrence of
      consecutive Calphaatoms with relatively high B values. The distribution of CCs
      and its relation to the mean difference between the B values of Calpha and Cbeta
      atoms shows dependence on the package used for refinement (X-PLOR, PROLSQ or
      TNT). These observations reflect the differences in the way B-value constraints
      are handled in these packages. Further differences are discernible in the
      distributions for proteins refined using the same package. It is likely that
      these differences are related to the different refinement protocols or weighting
      schemes followed by investigators. The resolution of these issues is important
      for evolving correct strategies for the refinement of the atomic displacement
      parameters in X-ray diffraction studies of proteins. Furthermore, it may be
      possible to develop refinement-validation tools by observing the features that
      are invariant in the distribution of atomic displacement parameters.

PMID- 10089409
TI  - Extending the limits of molecular replacement through combined simulated
      annealing and maximum-likelihood refinement.
AB  - Phases determined by the molecular-replacement method often suffer from model
      bias. In extreme cases, the refinement of the atomic model can stall at high free
      R values when the resulting electron-density maps provide little indication of
      how to correct the model, sometimes rendering even a correct solution unusable.
      Here, it is shown that several recent advances in refinement methodology allow
      productive refinement, even in cases where the molecular-replacement-phased
      electron-density maps do not allow manual rebuilding. In test calculations
      performed with a series of homologous models of penicillopepsin using either
      backbone atoms, or backbone atoms plus conserved core residues, model bias is
      reduced and refinement can proceed efficiently, even if the initial model is far
      from the correct one. These new methods combine cross-validation, torsion-angle
      dynamics simulated annealing and maximum-likelihood target functions. It is also
      shown that the free R value is an excellent indicator of model quality after
      refinement, potentially discriminating between correct and incorrect molecular
      replacement solutions. The use of phase information, even in the form of bimodal
      single-isomorphous-replacement phase distributions, greatly improves the radius
      of convergence of refinement and hence the quality of the electron-density maps,
      further extending the limits of molecular replacement.

PMID- 10089410
TI  - SFCHECK: a unified set of procedures for evaluating the quality of macromolecular
      structure-factor data and their agreement with the atomic model.
AB  - In this paper we present SFCHECK, a stand-alone software package that features a
      unified set of procedures for evaluating the structure-factor data obtained from
      X-ray diffraction experiments and for assessing the agreement of the atomic
      coordinates with these data. The evaluation is performed completely
      automatically, and produces a concise PostScript pictorial output similar to that
      of PROCHECK [Laskowski, MacArthur, Moss & Thornton (1993). J. Appl. Cryst. 26,
      283-291], greatly facilitating visual inspection of the results. The required
      inputs are the structure-factor amplitudes and the atomic coordinates. Having
      those, the program summarizes relevant information on the deposited structure
      factors and evaluates their quality using criteria such as data completeness,
      structure-factor uncertainty and the optical resolution computed from the
      Patterson origin peak. The dependence of various parameters on the nominal
      resolution (d spacing) is also given. To evaluate the global agreement of the
      atomic model with the experimental data, the program recomputes the R factor, the
      correlation coefficient between observed and calculated structure-factor
      amplitudes and Rfree (when appropriate). In addition, it gives several estimates
      of the average error in the atomic coordinates. The local agreement between the
      model and the electron-density map is evaluated on a per-residue basis,
      considering separately the macromolecule backbone and side-chain atoms, as well
      as solvent atoms and heterogroups. Among the criteria are the normalized average
      atomic displacement, the local density correlation coefficient and the polymer
      chain connectivity. The possibility of computing these criteria using the omit
      map procedure is also provided. The described software should be a valuable tool
      in monitoring the refinement procedure and in assessing structures deposited in
      databases.

PMID- 10089411
TI  - Difference density quality (DDQ): a method to assess the global and local
      correctness of macromolecular crystal structures.
AB  - Methods for the evaluation of the accuracy of crystal structures of proteins and
      nucleic acids are of general importance for structure-function studies as well as
      for biotechnological and biomedical research based upon three-dimensional
      structures of biomacromolecules. The structure-validation program DDQ (difference
      density quality) has been developed to complement existing validation procedures.
      The DDQ method is based on the information present in a difference electron
      density map calculated with the water molecules deliberately omitted from the
      structure-factor calculation. The quality of a crystal structure is reflected in
      this difference map by (i) the height of solvent peaks occurring at physical
      chemically reasonable positions with respect to protein and ligand atoms and (ii)
      the number and height of positive and negative 'shift' peaks next to protein
      atoms. The higher the solvent peaks and the lower the shift peaks, the better the
      structure is likely to be. Moreover, extraneous positive density due to an
      incomplete molecular model is also monitored, since this is another indicator of
      imperfections in the structure. Automated analysis of these types of features in
      difference electron densities is used to quantify the local as well as global
      accuracy of a structure. In the case of proteins, the DDQ structure-validation
      method is found to be very sensitive to small local errors, to omitted atoms and
      also to global errors in crystal structure determinations.

PMID- 10089412
TI  - Improved free R factors for cross-validation of macromolecular structure -
      importance for real-space refinement.
AB  - Improvements in free R cross-validation are based on changed scaling procedures
      and the use, in map calculation, of estimates of the validation amplitudes which
      are independent of the actual observed values. The deleterious effects of the
      omitted test data are mitigated by reduction of the test-set size, which is made
      possible by constraining test and working sets to share the same scaling
      coefficients, thereby reducing the degrees of freedom and the dependence of free
      R on data selection. Further improvements come with use of a modified free R
      factor, R freeTA. Instead of omitting the validation reflections from map
      calculation, their amplitudes are replaced by the average of resolution peers
      that is (nearly) independent of the actual cross-validation amplitudes. The
      improvements are relevant to model building, phase refinement by density
      modification and especially to real-space refinement. Although for real data at
      about 3 A resolution, free R factors of about 0.25 are affected little, the
      precision of the structure is improved by about 0.1 A. Tests with simulated data
      show that with good agreement between observed and calculated amplitudes (as in
      very high resolution studies or simulated refinement tests), free R factors can
      be improved by factors greater than two.

PMID- 10089413
TI  - Locating proper non-crystallographic symmetry in low-resolution electron-density
      maps with the program GETAX.
AB  - Non-crystallographic symmetry averaging for improving and extending an initial
      set of phases can be crucial at an early stage of a protein structure analysis. A
      method is described which detects the position of a proper rotation axis in a
      surprisingly poor electron-density map and is fast enough to run through a large
      number of axis orientations. It uses a simple multimer mask to define the
      searching unit, which is then shifted through the whole unit cell looking for the
      position with the highest correlation coefficient between the interrelated parts.
      Appropriate weighting and averaging enhances the signal-to-noise ratio. Examples
      of the application of this algorithm are given. The use of the local rotation
      axis for phasing is commented on. A search of the Protein Data Bank showed that
      27% of the unique crystal forms contain proper local n-fold axes, which could
      have been located with the presented method.

PMID- 10089414
TI  - On 'globbicity' of low-resolution protein structures.
AB  - Using Harker's [Harker (1953). Acta Cryst. 6, 731-736] idea of spherically
      averaged polyatomic groups or 'globs' as the units of structure suitable for
      analyzing low-resolution diffraction data from protein crystals, 'globbic'
      scattering factors have been calculated for main-chain peptide units and amino
      acid side-chain groups to 3 A resolution via Debye's [Debye (1915). Ann. Phys.
      (Leipzig), 46, 809-823] scattering formula. It is shown that the scattering
      factors are insensitive to intra-globbic conformational variation and can be
      approximated fairly well by a single-Gaussian formula, i.e. fg(s) = Zg exp(
      1.7Zgs2), where s = (sin theta)/lambda and Zg is the total electron count for the
      atoms of the glob. Phase errors due to the globbic approximation and their effect
      on electron-density maps at 3.5 A resolution have been assessed via calculations
      for the crambin structure; this analysis indicates that the globbic scattering
      factors will be useful in efforts to develop procedures for direct-methods
      phasing of diffraction data to approximately 3.5 A resolution from protein
      crystals.

PMID- 10089415
TI  - Estimating unobserved reflection intensities in Laue diffraction by the maximum
      entropy method.
AB  - In protein crystallography, the use of low-resolution reflections is important in
      defining the molecular mask and polypeptide backbone. However, in Laue data
      collection, the loss of low-resolution reflection data (>2dmin) can be as high as
      40-50%, even after the deconvolution of multiples. To estimate the reflection
      intensities that are not recorded in data collection, a new method is presented
      based on maximizing the entropy of the Patterson function subject to the
      constraints imposed by the intensities of the observed reflections. The method
      has been tested with Laue diffraction data from hen egg-white lysozyme. All
      unobserved reflections within 5 A resolution were estimated, and their inclusion
      in the electron-density-map calculation significantly improved the connectivity.
      This method could also be applied to improve the completeness of monochromatic
      data.

PMID- 10089416
TI  - Ab initio phasing using molecular envelope from solution X-ray scattering.
AB  - Solving the phase problem is the crucial and quite often the most difficult and
      time-consuming step in crystallographic structure determination. The traditional
      methods of isomorphous replacement (MIR or SIR) and molecular replacement require
      the availability of an isomorphous heavy-atom derivative or the structure of a
      homologous protein, respectively. Here, a method is presented which utilizes the
      low-resolution molecular shape determined from solution X-ray scattering data for
      the molecular search. The molecular shape of a protein is an important structural
      property and can be determined directly by the small-angle scattering technique.
      The idea of locating this molecular shape in the crystallographic unit cell has
      been tested with experimental diffraction data from nitrite reductase (NiR). The
      conventional Patterson search proved to be unsuccessful, as the intra-envelope
      vectors are uniformly distributed and do not match those of intra-molecular (atom
      to-atom) vectors. A direct real-space search for orientation and translation was
      then performed. A self-rotation function using 2.8 A crystallographic data
      yielded the polar angles of the non-crystallographic threefold axis. Knowledge of
      the orientation of this axis reduces the potential six-dimensional search to four
      (Eulerian angle gamma and three translational parameters). The direct four
      dimensional search within the unit cell produced a clear solution. The electron
      density map based on this solution agrees well with the known structure, and the
      phase error calculated from the map was 61 degrees within 20 A resolution. It is
      anticipated that the low-resolution envelope can be used as a starting model for
      phase extension by the maximum-entropy and density-modification method.

PMID- 10089417
TI  - Efficient anisotropic refinement of macromolecular structures using FFT.
AB  - This paper gives the equations for the use of fast Fourier transformations in
      individual atomic anisotropic refinement. Restraints on bonded atoms, on the
      sphericity of each atom and between non-crystallographic symmetry related atoms
      are described. These have been implemented in the program REFMAC and its
      performance with several examples is analysed. All the tests show that
      anisotropic refinement not only reduces the R value and Rfree but also improves
      the fit to geometric targets, indicating that this parameterization is valuable
      for improving models derived from experimental data. The computer time taken is
      comparable to that for isotropic refinements.

PMID- 10089418
TI  - Murine class I major histocompatibility complex H-2Dd: expression, refolding and
      crystallization.
AB  - A truncated soluble form of the murine class I major histocompatibility antigen
      complex H-2Dd was cloned using an Escherichia coli based system. It was
      expressed, refolded in vitro and crystallized in a complex with murine beta2
      microglobulin and the peptide RGPGRAFVTI from the V3-loop of the gp160 HIV-1
      protein. Crystals belonging to the space group P212121 with cell dimensions a =
      51.3, b = 92.5, c = 108.8 A were obtained using two different crystallization
      conditions. The crystals contain one complex per asymmetric unit and diffract to
      at least 2.4 A resolution.

PMID- 10089419
TI  - Crystallization of Escherichia coli RuvA complexed with a synthetic Holliday
      junction.
AB  - During homologous recombination in Escherichia coli the RuvA, B and C proteins
      interact specifically with the Holliday junction formed by the action of RecA to
      promote the strand-exchange reaction. RuvA, a homotetrameric protein of molecular
      weight 88 kDa, has been overexpressed in E. coli, purified and co-crystallized
      with a synthetic Holliday junction substrate made from four 18-base
      deoxyoligonucleotides. Crystals were grown using the hanging-drop vapour
      diffusion method with sodium acetate as the precipitant. The crystals diffract to
      a resolution of 6 A and belong to the monoclinic system, space group C2, with
      cell parameters a = 148, b = 148, c = 106 A and beta = 123 degrees. The X-ray
      analysis of these crystals should reveal the structure of the Holliday junction
      and its mode of binding to RuvA, providing new insights into the molecular
      mechanism of genetic recombination.

PMID- 10089420
TI  - Purification, crystallization and initial X-ray analysis of the C1 subunit of the
      astaxanthin protein, V600, of the chondrophore Velella velella.
AB  - The subunit C1 of the carotenoid-binding protein, V600, of the chondrophore
      Velella velella has been purified and crystallized. The crystals, which were
      grown by the vapour-diffusion method from ammonium sulfate as the major
      precipitant, diffract beyond 3 A and show little radiation damage over long
      periods (greater than 100 h) on a Cu Kalpha rotating-anode X-ray source. The
      space group of the crystals is P212121 with cell dimensions a = 42.0, b = 80.9, c
      = 110. 6 A.

PMID- 10089421
TI  - Crystallographic characterization of a novel protein SixA which exhibits phospho
      histidine phosphatase activity in the multistep His-Asp phosphorelay.
AB  - SixA has been isolated from Escherichia coli as the first protein to exhibit
      phospho-histidine phosphatase activity. Recent biochemical studies have shown
      that SixA is involved in the signal transduction of the His-Asp phosphorelay
      through the dephosphorylation of the histidine-containing phosphotransfer (HPt)
      domain of the anaerobic sensor kinase ArcB. Crystals of SixA were obtained using
      a hanging-drop vapour-diffusion method with polyethylene glycol and calcium ions.
      Preliminary X-ray crystallographic analysis revealed that the crystals belonged
      to space group P212121 with unit-cell dimensions a = 39.26, b = 48.62 and c =
      83.18 A, having one molecule in the crystallographic asymmetric unit. The
      intensity data were collected up to 1.5 A resolution using synchrotron radiation.

PMID- 10089422
TI  - Crystallization and preliminary X-ray analysis of human RCC1, the regulator of
      chromosome condensation.
AB  - RCC1, the regulator of chromosome condensation, is the guanine nucleotide
      exchange factor (GEF) of the GTP-binding protein Ran. Its GEF activity on Ran
      makes it a key element in nucleo-cytoplasmic transport and cell-cycle regulation.
      Crystals of human RCC1 suitable for X-ray analysis have been obtained using the
      seeding technique in hanging drops with sodium citrate as a precipitant. The
      crystals diffract to 1.7 A at 100 K and belong to the space group P1, with unit
      cell parameters a = 49.5, b = 84.3, c = 84.9 A, alpha = 113.0, beta = 103.9,gamma
      = 103.3 degrees. The Matthews parameter (Vm) and the self-rotation function are
      consistent with three molecules in the unit cell, which is confirmed by the
      averaged single isomorphous replacement (SIR) electron-density map.

PMID- 10089423
TI  - Crystallization and preliminary X-ray data for the human transthyretin-retinol
      binding protein (RBP) complex bound to an anti-RBP Fab.
AB  - A macromolecular complex of human transthyretin, human retinol-binding protein
      and an anti-retinol-binding-protein Fab was crystallized by vapour diffusion in
      sitting drops. Diffraction from these crystals at cryogenic temperatures was
      consistent with the space group C222, with cell parameters a = 159.34, b = 222.40
      and c = 121.27 A. Crystals diffracted to a resolution limit of 3.36 A using
      synchrotron radiation. Based on a 2:2:1 stoichiometry for the Fab-retinol-binding
      protein-transthyretin complex and the presence of one such complex per asymmetric
      unit, a reasonable Vm coefficient of 2.74 A3 Da-1 could be estimated.

PMID- 10089424
TI  - Oligonucleotides with 1,5-anhydrohexitol nucleoside building blocks:
      crystallization and preliminary X-ray studies of h(GTGTACAC).
AB  - Hexitol nucleic acids are oligonucleotides built up from natural nucleobases and
      a phosphorylated 1,5-anhydrohexitol backbone. The anhydrohexitol oligonucleotide
      h(GTGTACAC) was synthesized using phosphoramidite chemistry and standard
      protecting groups. Crystals of h(GTGTACAC) were obtained at either 279 or 289 K
      by the hanging-drop vapour-diffusion technique using a 24-matrix screen for
      nucleic acid fragments. The crystals diffract beyond 2.0 A resolution and belong
      to the hexagonal space group P6222 (or P6422) with unit-cell parameters a = 36.42
      and c = 63.33 A.

PMID- 10089425
TI  - Crystallization of the dimerization-initiation site of genomic HIV-1 RNA:
      preliminary crystallographic results.
AB  - The genomic RNA of all retroviruses is encapsidated in virions as a dimer of
      single-stranded chains held together near their 5'-end. For HIV-1, the initial
      site of dimerization has been shown to be a hairpin with a nine-residue loop
      containing a self-complementary sequence of six residues. This structure is
      proposed to promote dimerization by loop-loop interaction and formation of a so
      called 'kissing complex'. A 23-nucleotide RNA strand containing the loop enclosed
      by a seven base-pair stem has been synthesized. This oligomer was crystallized by
      the vapour-diffusion method at 310 K, pH 6.5, with methyl-pentanediol as the
      precipitant agent in the presence of MgCl2, KCl and spermine. Quasi-complete
      diffraction data were obtained at 2.7 A resolution with a conventional X-ray
      source and at 2.3 A resolution on a synchrotron beamline. The space group is
      P3121 or its enantiomorph P3221, with cell parameters a = b = 60. 1, c = 65.9 A
      at ambient temperature, or a = b = 59.0, c = 64.3 A in a nitrogen-gas stream.
      There are two oligomers per asymmetric unit as determined from absorbance
      measurements of a dissolved crystal whose volume was carefully determined. In
      some cases, either perfectly or partially twinned crystals were obtained. Perfect
      twinning is detected by an apparent hexagonal symmetry and yields unusable
      crystallographic data, whilst partial twinning yields usable data after adequate
      processing. Structure solution is under way by searching for heavy-atom
      derivatives and systematically substituting bromo- or iodo-uridines for uridines.

PMID- 10089426
TI  - Crystallization and preliminary X-ray analysis of the bacterial ATP-binding
      cassette (ABC) protein MalK.
AB  - The ATP-binding protein, MalK, of the bacterial ABC (ATP-binding-cassette)
      transport complex MalFGK2 provides the energy for the translocation of maltose
      and maltodextrins across the cytoplasmic membrane. The MalK protein from
      Salmonella typhimurium was overexpressed in Escherichia coli and crystallized by
      the hanging-drop method using (NH4)2SO4as a precipitant. The crystals belong to
      space group P6x22 (most probably x = 1 or 5) with cell dimensions a = 181.8 and c
      = 182.5 A, corresponding to three or four molecules per asymmetric unit. They
      diffract to a resolution of about 3 A on a synchrotron X-ray source and are
      suitable for structure determination.

PMID- 10089427
TI  - Cloning, expression and crystallization of pyrimidine nucleoside phosphorylase
      from Bacillus stearothermophilus.
AB  - Pyrimidine nucleoside phosphorylase (PYNP) from B. stearothermophilus has been
      cloned and purified for crystallization. Crystals of a potential protein
      inhibitor complex have been prepared by co-crystallization techniques using the
      substrate analog pseudouridine. These crystals provide good-quality diffraction
      images to 2.7 A and belong to space group P21. The asymmetric unit contains the
      dimer structure of PYNP with unit-cell parameters a = 53.9, b = 71.9, c = 123.3 A
      and beta = 96.9 degrees.

PMID- 10089428
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of the
      yeast phosphorelay protein YPD1.
AB  - YPD1 is a yeast osmoregulatory protein that functions in a phosphorelay signal
      transduction pathway. YPD1 has been expressed in Escherichia coli, purified to
      homogeneity and crystallized. The crystals were obtained by hanging-drop vapor
      diffusion using PEG 4000 as a precipitant. Preliminary X-ray diffraction analysis
      indicates that the crystals belong to tetragonal space group P43212 or P41212
      with unit-cell dimensions a = b = 52.71, c = 244.02 A. X-ray data to 2.7 and 3.0
      A have been collected from native crystals and a heavy-atom derivative,
      respectively. Positions for two Hg atoms have been located by analysis of
      difference Patterson maps.

PMID- 10089429
TI  - A thermostable xylose isomerase from Thermus caldophilus: biochemical
      characterization, crystallization and preliminary X-ray analysis.
AB  - A highly thermostable xylose isomerase from Thermus caldophilus has been
      expressed in Escherichia coli. The purified enzyme has an optimum temperature of
      363 K. It has been crystallized at room temperature using ammonium sulfate as a
      precipitant. The crystal belongs to the orthorhombic space group P212121, with
      unit-cell parameters a = 84.35, b = 123.60, c = 140.24 A. The presence of one
      molecule of tetrameric xylose isomerase in the asymmetric unit gives a crystal
      volume per protein mass (Vm) of 2.1 A3 Da-1 and a solvent content of 41% by
      volume. The crystals initially showed diffraction to 1.7 A Bragg spacing with
      synchrotron X-rays, and a set of native data extending to 2.3 A resolution has
      been collected.

PMID- 10089430
TI  - Crystallization and preliminary crystallographic analysis of an NADH oxidase that
      functions in peroxide reduction in Thermus aquaticus YT-1.
AB  - NADH oxidase from Thermus aquaticus is a thermostable flavoenzyme that is similar
      in amino-acid sequence and other properties to the flavoenzyme component of the
      NADH peroxidase systems from Salmonella typhimurium and Amphibacillus xylanus.
      The enzyme has been isolated from T. aquaticus and crystallized using the hanging
      drop method of vapour diffusion with sodium citrate as a precipitant at pH 8.5.
      The crystals belong to the hexagonal space group P622 with unit-cell dimensions a
      = b = 89.9, c = 491.6 A, and diffract to 2.5 A resolution.

PMID- 10089431
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      results from Campylobacter jejuni ferritin.
AB  - The prokaryotic ferritin gene of Campylobacter jejuni was overexpressed in
      Escherichia coli under control of the bacteriophage T7 promoter and the protein
      (Cj-FTN) purified. Preliminary crystallization experiments have been performed
      using the hanging-drop vapour-diffusion method with ammonium sulfate as the
      precipitant. Diffraction studies show the crystals belong to the I432 space group
      (a = 151.52 A). Structure solution by molecular replacement is in progress while
      crystal quality improvement is carried out.

PMID- 10089432
TI  - Crystallization and characterization of a fragment of pseudouridine synthase RluC
      from Escherichia coli.
AB  - RluC from E. coli is the enzyme responsible for catalyzing the isomerization of
      uridines 955, 2504 and 2580 in 23S rRNA to pseudouridine. Histidine-tagged RluC
      was cloned, overexpressed and purified by nickel-affinity chromatography. A
      proteolytically derived fragment of the enzyme consisting of residues 89-319 has
      been shown to retain catalytic activity. Crystals of this fragment, grown by
      precipitation with sodium acetate at pH 8.0, belong to space group P321, with
      unit-cell dimensions a = b = 97.1, c = 86.3 A and have two molecules in the
      crystallographic asymmetric unit. The flash-frozen crystals diffract X-rays to at
      least 2.3 A resolution and appear suitable for crystal structure determination.

PMID- 10089433
TI  - Crystallization and preliminary crystallographic studies of the anthranilate
      synthase partial complex from Salmonella typhimurium.
AB  - Anthranilate synthase catalyzes the first step in the biosynthesis of tryptophan
      from chorismate. The anthranilate synthase partial complex from Salmonella
      typhimurium has been crystallized in space group P21212 with unit-cell dimensions
      a = 116.7, b = 101.2 and c = 66.8 A.

PMID- 10089434
TI  - Crystallization and preliminary X-ray study of iso-2 azurin from the
      methylotrophic bacterium, Methylomonas J.
AB  - The obligate methylotroph Methylomonas J possesses two distinct azurins. The iso
      2 azurin, which functions as an electron acceptor for methylamine dehydrogenase,
      has been crystallized using two kinds of precipitants: PEG 4000 and ammonium
      sulfate. The crystals precipitated with PEG belong to the monoclinic system,
      space group P21, with unit-cell parameters a = 32.96, b = 33.67, c = 47.34 A and
      beta = 101.35 degrees. The crystals precipitated with ammonium sulfate belong to
      the orthorhombic system, space group C2221, with unit-cell parameters a = 31.52,
      b = 62.49 and c = 135.41 A. The crystals diffract to 1.6 and 1.9 A resolution,
      respectively, and were suitable for X-ray crystallographic studies. A Patterson
      search is being conducted using the recently reported structure of Alcaligenes
      xylosoxidans NCIMB 11015 as a starting model.

PMID- 10089435
TI  - Purification, crystallization and preliminary X-ray studies of two isoforms of
      Rubisco from Alcaligenes eutrophus.
AB  - Two different isoforms of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) from Alcaligenes eutrophus have been purified and crystallized. Both
      isoforms crystallize in space group P43212. Crystals of isoform I (unit-cell
      dimensions a = 112.0 and c = 402.7 A) diffract to 2.7 A, whereas isoform II (unit
      cell dimensions a = 111.8 and c = 400.0 A) presently diffract to 3.2 A, using
      synchrotron radiation in both cases.

PMID- 10089436
TI  - Use of streptococcal protein G in obtaining crystals of an antibody Fab fragment
      in complex with a meningococcal antigen.
AB  - Crystals have been obtained of an antibody Fab fragment grown in the presence of
      a single domain from streptococcal protein G and a ten amino-acid peptide
      corresponding to the P1.7 serosubtype antigen from the human pathogen Neisseria
      meningitidis. Crystal trials using the Fab fragment and peptide antigen alone
      were unsuccessful, but the inclusion of a protein G domain provided an additional
      variable that generated suitable crystals. Crystals are in space group P21 with
      unit-cell parameters a = 43.60, b = 63.42, c = 89.63 A, beta = 98.58 degrees and
      a data set has been collected to 2.9 A resolution using synchrotron radiation.
      The inclusion of protein G is likely to be of general utility for the
      crystallization of Fab-antigen complexes.

PMID- 10089437
TI  - Crystallization and preliminary X-ray diffraction studies of phospholipase D from
      Streptomyces antibioticus.
AB  - Phospholipase D (E.C. 3.1.4.4) from Streptomyces antibioticus has been
      crystallized in six crystal forms using the hanging-drop vapour-diffusion method.
      The type III and V crystals belong to monoclinic and hexagonal systems,
      respectively. All of the other crystal forms, types I, II, IV and VI, belong to
      orthorhombic space group P212121. Of these four types, the type VI crystals are
      suitable for X-ray structure determination. Crystal data for type VI crystals
      are: a = 50.1, b = 98.7, c = 107.6 A, V = 532100 A3, Z = 4 and Vm = 2.47 A3 Da-1.
      Type VI crystals diffract to at least 2.3 A resolution. A total of 11295
      independent reflections to 3 A resolution have been collected from a type VI
      crystal using a conventional X-ray source, and its structural analysis is
      currently being conducted using isomorphous replacement methods.

PMID- 10089438
TI  - Crystallization and preliminary crystallographic analysis of the endo
      polygalacturonase from Erwinia carotovora ssp. carotovora.
AB  - Crystals of endo-polygalacturonase from Erwinia carotovora ssp. carotovora have
      been grown from polyethylene glycol 6000 by the hanging-drop method.
      Polygalacturonase is important in the virulence of this plant pathogen. The
      protein crystallizes in space group C2 with unit-cell parameters a = 81.3, b =
      53.0, c = 103.1 A, beta = 112.6 degrees and with a single molecule in the
      asymmetric unit. The crystals diffract to 1.9 A.

PMID- 10089439
TI  - Preliminary crystallographic characterization of an in vitro evolved biotin
      binding RNA pseudoknot.
AB  - A biotin-binding RNA pseudoknot developed through in vitro selection has been
      crystallized using the hanging-drop vapor-phase diffusion method. The X-ray
      diffraction data indicate that the crystals belong to the space group P4222 with
      unit-cell parameters a = b = 55.2, c = 62.7 A and alpha = beta = gamma = 90
      degrees. The crystals are 120 x 80 x 40 microm and VM = 2.17 A3 Da-1. The
      crystals diffract to 2.8 A.

PMID- 10089440
TI  - Preliminary characterization of crystals of an in vitro evolved cyanocobalamin
      (vitamin B12) binding RNA.
AB  - A 35-nucleotide pseudoknot that binds vitamin B12 been isolated using systematic
      evolution of ligands by exponential enrichment (SELEX). Affinity chromatography
      was used to purify functional, properly folded molecules and the hanging-drop
      vapor-diffusion method was used to crystallize this aptamer. Two crystal forms
      have been obtained and the preliminary crystallographic characterization is
      reported here. Both crystal forms (space groups I222 or I212121 and C2221)
      diffract to 2.9 A and should prove sufficient for structure determination.

PMID- 10089441
TI  - Crystallization and preliminary crystallographic analysis of the pyruvate
      ferredoxin oxidoreductase from Desulfovibrio africanus.
AB  - For the first time, crystals of a pyruvate-ferredoxin oxidoreductase (PFOR)
      suitable for X-ray analysis have been obtained. This enzyme catalyzes, in
      anaerobic organisms, the crucial energy-yielding reaction of pyruvate
      decarboxylation to acetylCoA. Polyethylene glycol and divalent metal cations have
      been used to crystallize the PFOR from the sulfate-reducing bacterium
      Desulfovibrio africanus. Two different orthorhombic (P212121 ) crystal forms have
      been grown with unit-cell dimensions a = 86.1, b = 146.7, c = 212.5 A and a =
      84.8, b = 144.9, c = 203.0 A. Both crystals diffract to 2.3 A resolution using
      synchrotron radiation.

PMID- 10089442
TI  - Crystallization and preliminary X-ray analysis of Escherichia coli methionyl
      tRNAMet(f) formyltransferase complexed with formyl-methionyl-tRNAMet(f).
AB  - The structure of methionyl-tRNAfMet(f) formyltransferase from E. coli, a
      monomeric protein of 34 kDa, has previously been determined at 2.0 A resolution.
      In the present work, this enzyme was crystallized as a complex with its
      macromolecular product, the initiator formyl-methionyl-tRNAfMet(f) (25 kDa).
      Polyethylene glycol 5000 monomethylether was used as a precipitating agent. The
      crystals are orthorhombic and have unit-cell parameters a = 201.7, b = 68.1, c =
      86.4 A. They belong to space group P21212 and diffract to 2.8 A resolution. The
      structure is being solved with the help of a mercury derivative.

PMID- 10089443
TI  - Decamers observed in the crystals of bovine pancreatic trypsin inhibitor.
AB  - The structure of bovine pancreatic trypsin inhibitor (BPTI) has been solved at
      2.1 A resolution in a new crystal form (space group P6422 with unit-cell
      dimensions a = b = 95.0, c = 158.1 A). The asymmetric unit is a pentamer, but a
      decamer is created by application of crystallographic symmetry. The decamer of
      BPTI is only the fourth such assembly reported to date in the Protein Data Bank.

PMID- 10089444
TI  - Expression, purification and preliminary X-ray analysis of a fibrillarin homolog
      from Methanococcus jannaschii, a hyperthermophile.
AB  - Fibrillarin plays a central role in ribosome biogenesis as a ribosomal RNA
      processing protein. A Methanococcus jannaschii homolog of fibrillarin has been
      overexpressed, purified and crystallized. Crystals belong to the C2 space group
      with unit-cell parameters a = 121.4, b = 43.2, c = 55.3 A, beta = 96.9 degrees.
      Under flash-frozen conditions and using synchrotron radiation, the crystals
      diffract to 1.8 A resolution. For structural determination, a selenomethionine
      derivative of the protein has also been crystallized.

PMID- 10089445
TI  - A series of bioactivity-variant neurotoxins from scorpion Buthus martensii
      Karsch: purification, crystallization and crystallographic analysis.
AB  - Three bioactivity-variant neurotoxins, BmK M1, M4 and M8, have been purified from
      Chinese scorpion BmK venom. They possess distinct toxic activities against mice
      in vivo. These proteins also have different electrostatic properties. The
      relative toxicities for BmK M1, M4 and M8 are 13.3:2.5:1 which, surprisingly,
      correspond to their respective pI values ranging from basic to acidic 9.01, 7.53
      and 5.30, respectively. They have been crystallized in different crystal forms as
      orthorhombic, hexagonal and monoclinic, respectively. These crystals can diffract
      to 1.2 (BmK M1), 1.3 (BmK M4) and 1.8 A (BmK M8) resolution and have been used in
      data collection. These toxins produced by natural mutagenesis or gene divergence
      should represent functionally distinct states, thereby forming a valuable system
      for studying structure-function relationships. The unusual relatively acidic
      component that first appeared in this series also provides a new concept for a
      more comprehensive understanding of scorpion neurotoxins.

PMID- 10089446
TI  - Medium temperature, 310 K, provides single crystals of orotate
      phosphoribosyltransferase from Thermus thermophilus.
AB  - Crystallization of orotate phosphoribosyltransferase from a thermophilic
      organism, Thermus thermophilus, was achieved using the hanging-drop vapour
      diffusion method coupled with a macroseeding starter. Small needle-like
      microcrystals were grown in a fresh protein solution in the presence of 2-methyl
      2,4-pentanediol at 298 K or below. Although these normal temperature conditions
      caused stacking crystallization, an increase of temperature to 310 K permitted
      crystal growth. This was because of increased enzyme solubility at the higher
      temperature. The crystal was found to belong to the monoclinic space group
      P21with unit-cell parameters a = 44.4, b = 59.6, c = 67.8 A and beta = 98.3
      degrees.

PMID- 10089447
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of uracil phosphoribosyltransferase of Toxoplasma gondii.
AB  - Recombinant uracil phosphoribosyltransferase (UPRT) enzyme of Toxoplasma gondii
      was expressed in Escherichia coli and purified from the cell-free extract by a
      combination of chromatographic steps. The recombinant protein was enzymatically
      active when tested in an in vitro UPRT assay. The purified protein was
      crystallized using the hanging-drop vapor-diffusion technique with ammonium
      phosphate as precipitant. The crystallized protein also exhibited UPRT activity.
      Crystals diffract to 2.4 A resolution and belong to space group P3121 or P3221
      with unit-cell dimensions a = b = 119.9, c = 70.8 A and two molecules per
      asymmetric unit.

PMID- 10089448
TI  - Purification and crystallization of a novel membrane-anchored protein: the
      Schistosoma haematobium serpin.
AB  - A unique serine-protease inhibitor (serpin) of the blood fluke S. haematobium has
      been crystallized. It is an antitrypsin with an unusual residue (phenylalanine)
      at its reactive center. Unlike any known member of this gene family, it is a
      membrane-anchored protein on the surface of the parasite. The location of this
      serpin and immunological response to the protein indicate that it may play a
      important role in host-parasite interaction. The crystals belong to the trigonal
      space group P3221 or P3121 with unit-cell parameters a = b = 64.7, c = 186.7 A,
      alpha = 90.0, beta = 90.0, gamma = 120.0 degrees. There is one molecule per
      asymmetric unit and the crystals diffracted to 2.2 A.

PMID- 10089449
TI  - A general method for co-crystallization of concanavalin A with carbohydrates.
AB  - A small grid of conditions has been developed for co-crystallization of the plant
      lectin concanavalin A (conA) and polysaccharides. Crystals have been obtained of
      complexes of conA with alpha1-2 mannobiose, 1-methyl alpha1-2 mannobiose,
      fructose, a trisaccharide and a pentasaccharide. The crystals diffract to
      resolutions of 1. 75-2.7 A using a copper rotating-anode source. The crystals are
      grown in the presence of polyethylene glycol 6K [10-20%(w/v)] at around pH 6.0.
      Optimization for each particular carbohydrate requires small adjustments in the
      conditions; however, all complexes give some crystalline precipitate in this
      limited grid. The alpha1-2 mannobiose complex crystals diffract to 1.75 A with
      space group I222 and cell dimensions a = 91.7, b = 86.8, c = 66.6 A. One monomer
      is present in the asymmetric unit. The 1-methyl alpha1-2 mannobioside complex
      crystallizes in space group P212121, cell dimensions a = 119. 7, b = 119.7, c =
      68.9 A and diffract to 2.75 A. One tetramer is present in the asymmetric unit.
      Two crystal forms of the conA-fructose complex have been obtained. The first has
      space group P212121, cell dimensions a = 121.7, b = 119.9, c = 67.3 A with a
      tetramer in the asymmetric unit and diffracts to 2.6 A. The second crystallizes
      in space group C2221, cell dimensions a = 103.3, b = 117.9, c = 254.3 A with two
      dimers in the asymmetric unit and diffracts to 2.42 A. Structures and
      crystallization of the trisaccharide-conA and pentasaccharide-conA complexes have
      already been reported. In all complexes, the protein is found as a tetramer,
      although varying combinations of non-crystallographic and crystallographic
      symmetry are involved in generating the tetramer. The precise packing of the
      tetramer varies from crystal to crystal and it is likely that this variability
      facilitates crystallization.

PMID- 10089450
TI  - A plant-seed inhibitor of two classes of alpha-amylases: X-ray analysis of
      Tenebrio molitor larvae alpha-amylase in complex with the bean Phaseolus vulgaris
      inhibitor.
AB  - The alpha-amylase from Tenebrio molitor larvae (TMA) has been crystallized in
      complex with the alpha-amylase inhibitor (alpha-AI) from the bean Phaseolus
      vulgaris. A molecular-replacement solution of the structure was obtained using
      the refined pig pancreatic alpha-amylase (PPA) and alpha-AI atomic coordinates as
      starting models. The structural analysis showed that although TMA has the typical
      structure common to alpha-amylases, large deviations from the mammalian alpha
      amylase models occur in the loops. Despite these differences in the interacting
      loops, the bean inhibitor is still able to inhibit both the insect and mammalian
      alpha-amylase.

PMID- 10089451
TI  - International union of CrystallographyActa crystallographica section DNotes for
      AuthorsThese notes are also available from http://www. iucr.org/actad 

PMID- 10089452
TI  - Preliminary X-ray crystallographic analysis of the complex between the DNAase
      domain of colicin E9 and its cognate immunity protein.
AB  - We have crystallized and performed preliminary X-ray characterization of the
      complex between the DNAase domain of the E9 colicin and its cognate immunity
      protein Im9. The dissociation constant for this complex, Kd = 1 x 10(-16) M,
      reveals it to be one of the highest affinity protein-protein interactions known.
      Single crystals of the 1:1 complex were grown from microseeding experiments using
      PEG 4K as precipitant. The space group is P212121 with one molecule of complex in
      the asymmetric unit, and crystals contain approximately 43% solvent. These
      crystals are inherently non-isomorphous and so selenomethionine-derivatized
      protein has been prepared and crystals grown for MAD phasing experiments.

PMID- 10089453
TI  - Crystallization and preliminary X-ray analysis of the Rhodobacter capsulatus
      magnesium chelatase BchI subunit.
AB  - The Rhodobacter capsulatus BchI protein is one of three subunits of Mg chelatase,
      the enzyme which catalyzes the first committed step of chlorophyll and
      bacteriochlorophyll biosynthesis. The BchI protein was produced with an inducible
      T7 RNA polymerase expression system in Escherichia coli. The protein was purified
      from the soluble cell-extract fraction and crystallized from polyethylene glycol
      solution. The crystals diffract to a minimum Bragg spacing of 2.1 A. The space
      group is P63 with unit-cell dimensions a = b = 90.6, c = 84.1 A.

PMID- 10089454
TI  - Purification, crystallization and preliminary structural studies of dTDP-6-deoxy
      D-xylo-4-hexulose 3,5-epimerase (RmlC), the third enzyme of the dTDP-L-rhamnose
      synthesis pathway, from Salmonella enterica serovar typhimurium.
AB  - L-Rhamnose is an essential component of the cell wall of many pathogenic
      bacteria. Its precusor, dTDP-L-rhamnose, is synthesized from alpha-D-glucose-1
      phosphate and dTTP via a pathway requiring four distinct enzymes: RmlA, RmlB,
      RmlC and RmlD. RmlC was overexpressed in Escherichia coli. The recombinant
      protein was purified by a two-step protocol involving anion-exchange and
      hydrophobic chromatography. Dynamic light-scattering experiments indicated that
      the recombinant protein is monodisperse. Crystals were obtained using the sitting
      drop vapour-diffusion method with ammonium sulfate as precipitant. Diffraction
      data were collected on a frozen crystal to a resolution of 2.17 A. The crystal
      belongs to either space group P3121 or P3221, with unit-cell parameters a = b =
      71.56, c = 183.53 A and alpha = beta = 90, gamma = 120 degrees.

PMID- 10089455
TI  - Remarks about protein structure precision.
AB  - Full-matrix least squares is taken as the basis for an examination of protein
      structure precision. A two-atom protein model is used to compare the precisions
      of unrestrained and restrained refinements. In this model, restrained refinement
      determines a bond length which is the weighted mean of the unrestrained
      diffraction-only length and the geometric dictionary length. Data of 0.94 A
      resolution for the 237-residue protein concanavalin A are used in unrestrained
      and restrained full-matrix inversions to provide standard uncertainties sigma(r)
      for positions and sigma(l) for bond lengths. sigma(r) is as small as 0.01 A for
      atoms with low Debye B values but increases strongly with B. The results
      emphasize the distinction between unrestrained and restrained refinements and
      between sigma(r) and sigma(l). Other full-matrix inversions are reported. Such
      inversions require massive calculations. Several approximate methods are examined
      and compared critically. These include a Fourier map formula [Cruickshank (1949).
      Acta Cryst. 2, 65-82], Luzzati plots [Luzzati (1952). Acta Cryst. 5, 802-810] and
      a new diffraction-component precision index (DPI). The DPI estimate of sigma(r,
      Bavg) is given by a simple formula. It uses R or Rfree and is based on a very
      rough approximation to the least-squares method. Many examples show its
      usefulness as a precision comparator for high- and low-resolution structures. The
      effect of restraints as resolution varies is examined. More regular use of full
      matrix inversion is urged to establish positional precision and hence the
      precision of non-dictionary distances in both high- and low-resolution
      structures. Failing this, parameter blocks for representative residues and their
      neighbours should be inverted to gain a general idea of sigma(r) as a function of
      B. The whole discussion is subject to some caveats about the effects of
      disordered regions in the crystal.

PMID- 10089456
TI  - Structure of the side-by-side binding of distamycin to d(GTATATAC)2.
AB  - The 2.40 A resolution crystal structure of a side-by-side binding of distamycin A
      molecules to a DNA octamer d(GTATATAC)2 with an extended alternating TA sequence
      has been determined. The unit-cell parameters are a = 29.55, b = 42.18, c = 43.38
      A, beta = 96.56 degrees, space group P21, with two molecules in the asymmetric
      unit, in contrast to all previous side-by-side distamycin-DNA complexes which
      have only a single DNA strand and one drug molecule in the asymmetric unit. The
      structure was solved by the molecular-replacement method and refined to an R
      index of 21.0% using 3467 reflections [>/= 2sigma(F)]. The minor grooves of the
      DNA molecules bind two side-by-side antiparallel staggered distamycins spanning
      about five base pairs and virtually covering the entire length of the DNA. The
      octamer duplexes exhibit low-high alternations in the helical twist, sugar
      puckering and the C-O3' and O3'-P torsion angles, similar to the earlier side-by
      side complexes containing inosine bases. The molecules are stacked one over the
      other along the ac diagonal in an infinite pseudo-continuous helical column with
      no lateral interactions.

PMID- 10089457
TI  - Structure of dethiobiotin synthetase at 0.97 A resolution.
AB  - The crystal structure of the 224-residue protein dethiobiotin synthetase from
      Escherichia coli has been refined using X-ray diffraction data at 0.97 A
      resolution at 100 K. The model, consisting of 4143 protein atoms including 1859 H
      atoms and 436 solvent sites, was refined to a final R factor of 11.6% for all
      reflections, and has an estimated mean standard uncertainty for the atomic
      positions of 0.022 A, derived from inversion of the blocked matrix. The structure
      was refined with a full anisotropic model for the atomic displacement parameters
      using SHELX97. Stereochemical restraints were applied throughout the refinement.
      In the last cycles, the planarity of the peptide bonds was not restrained,
      resulting in a mean omega value of 179.6 degrees. Analysis of the most
      anisotropic regions of the protein shows that they form four clusters of
      residues. Alternate conformations for the side chains of 15 residues and for the
      main-chain atoms of six residues from three loops were included in the model. An
      analysis of C-HcO hydrogen bonds shows that such interactions occur rather
      frequently in DTBS; in total, 16 such hydrogen bonds were found. In the central
      beta-sheet, 13 C-HcO bonds between carbonyl O and Calpha H atoms were found.
      Other interactions of this type involve main-chain-side-chain and side-chain-side
      chain C-HcO bonds. The model includes 436 water sites, of which 233 molecules
      form the first hydration shell. Analysis of the protein-solvent interactions
      shows that about one third of the accessible surface of the enzyme is not covered
      by ordered solvent. No difference in propensity for ordered solvent close to
      hydrophilic or hydrophobic surface areas was found. The comparison of the 100 K
      structure with the structure of the enzyme determined at room temperature shows
      several regions with different conformation, including areas in the active site,
      suggesting that structural transitions can occur during flash freezing. This
      observation questions one of the basic assumptions in the analysis of enzymatic
      reaction mechanisms using cryocrystallography.

PMID- 10089458
TI  - Structure of the Rhizomucor miehei aspartic proteinase complexed with the
      inhibitor pepstatin A at 2.7 A resolution.
AB  - Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with pepstatin
      A grew in the orthorhombic space group P212121 and were isomorphous to native RMP
      crystals. The unit-cell dimensions are a = 41.52, b = 50.82, c = 172.71 A. There
      is one RMP-pepstatin A complex per asymmetric unit. The structure of the RMP
      pepstatin A complex has been refined to a crystallographic R value of 19.3% and
      an Rfree value of 28.0% at 2.7 A resolution. A pepstatin A molecule fits into the
      large substrate-binding cleft between the two domains of RMP in an extended
      conformation up to the alanine residue at the P2' position. The dipeptide
      analogue statine residue at the P3'-P4' position forms an inverse gamma-turn (P3'
      P1') with the statine residue at the P1-P1' position and its leucyl side chain
      binds back into the S1' subsite. The inhibitor interacts with the residues of the
      substrate-binding pocket by both hydrogen bonds and hydrophobic interactions. The
      hydroxyl group of the statine residue at the P1-P1' position forms hydrogen bonds
      with both catalytic aspartate residues (Asp38 and Asp237). This conformation
      mimics the expected transition state of the enzyme-substrate interaction. The
      binding of the inhibitor to the enzyme does not produce large distortions of the
      active site. No domain movement was observed compared with the native enzyme
      structure. However, the surface-flap region (residues 82-88) undergoes a
      conformational change, moving toward the inhibitor and becoming rigid owing to
      the formation of hydrogen bonds with the inhibitor. B-factor calculations of the
      two domains suggest that the C-terminal domain becomes more rigid in the complex
      than in the native structure.

PMID- 10089459
TI  - Determination of the structure of seleno-methionine-labelled hydroxymethylbilane
      synthase in its active form by multi-wavelength anomalous dispersion.
AB  - The enzyme hydroxymethylbilane synthase (HMBS, E.C. 4.3.1.8) catalyzes the
      conversion of porphobilinogen into hydroxymethylbilane, a key intermediate for
      the biosynthesis of heme, chlorophylls, vitamin B12 and related macrocycles. The
      enzyme is found in all organisms, except viruses. The crystal structure of the
      selenomethionine-labelled enzyme ([SeMet]HMBS) from Escherichia coli has been
      solved by the multi-wavelength anomalous dispersion (MAD) experimental method
      using the Daresbury SRS station 9.5. In addition, [SeMet]HMBS has been studied by
      MAD at the Grenoble ESRF MAD beamline BM14 (BL19) and this work is described
      especially with respect to the use of the ESRF CCD detector. The structure at
      ambient temperature has been refined, the R factor being 16.8% at 2. 4 A
      resolution. The dipyrromethane cofactor of the enzyme is preserved in its reduced
      form in the crystal and its geometrical shape is in full agreement with the
      crystal structures of authentic dipyrromethanes. Proximal to the reactive C atom
      of the reduced cofactor, spherical density is seen consistent with there being a
      water molecule ideally placed to take part in the final step of the enzyme
      reaction cycle. Intriguingly, the loop with residues 47-58 is not ordered in the
      structure of this form of the enzyme, which carries no substrate. Direct
      experimental study of the active enzyme is now feasible using time-resolved Laue
      diffraction and freeze-trapping, building on the structural work described here
      as the foundation.

PMID- 10089460
TI  - Mosaic spread characterization of microgravity-grown tetragonal lysozyme single
      crystals.
AB  - Mosaic spread values for crystals grown in microgravity were measured using
      synchrotron radiation. Full width at half maximum (FWHM) values for diffraction
      line profiles in the range 10-20" (arc seconds, 1" = 1 degrees /3600) were
      observed. These values are similar to those measured for crystals grown on earth
      using the gel-acupuncture method. The crystals analysed are composed of from two
      to five domains producing peaks having widths from 5 to 15". The distribution of
      these domains is neither homogeneous (with domains of lower quality concentrated
      in the centre of the crystal) nor isotropic (producing peaks whose width changes
      depending on the observation direction). Methodological aspects are also
      discussed, with special consideration of the effects of mosaic spread on the data
      collection procedures for high-resolution (low-intensity) reflections.

PMID- 10089461
TI  - In-situ measurement of rocking curves during lysozyme crystal growth.
AB  - The rocking curve of protein crystals contains a lot of useful information
      concerning crystal quality, most of which is lost owing to the superimposition of
      spurious features appearing in these fragile materials after growth, during
      handling and mounting. To minimize such data spoiling, an experimental setup to
      perform in situ X-ray diffraction experiments during crystal growth has been
      designed. The setup, which includes video observation to allow the correlation of
      crystal shape, size and growth rate with X-ray data, has been used to assess the
      mosaicity of tetragonal lysozyme crystals during crystal growth. The full width
      at half maximum (FWHM) of diffraction peaks collected from these crystals changes
      during the growth process as a (directly proportional) response to the growth
      rates and the different development of different domain blocks. These changes in
      the domain distribution and FWHM with time involve a 'zonation' of the crystals,
      which show very different rocking curves in different parts of their volume. The
      rocking curves recorded in situ from growing crystals are easier to understand
      than those from crystals that have suffered even minor handling.

PMID- 10089462
TI  - An accurate numerical model for calculating the equilibration rate of a hanging
      drop experiment.
AB  - A numerical model of the equilibration of a hanging-drop experiment has been
      developed and tested. To obtain accurate calculations with a given precipitant,
      the vapor pressure of water over water/precipitant solutions must be known for
      various concentrations of the precipitant. The calculations of the model are in
      excellent agreement with all available experimental data on hanging-drop
      equilibration when the necessary vapor pressures are known (ammonium sulfate and
      sodium chloride). By varying each of the relevant rate constants in the model,
      the rate-limiting step in the equilibration of a hanging drop is determined. This
      analysis clearly shows that the rate-limiting step is the diffusion of water
      vapor from the drop to the reservoir, which agrees with experimental findings.
      Since the diffusion of water vapor is the rate-limiting step, there is virtually
      no precipitant concentration gradient in the drop during equilibration. As a
      result, there is no gravity-induced convection owing to the equilibration. Thus,
      whereas gravity might have an effect during crystal growth, gravity does not
      affect the equilibration rate of a hanging-drop experiment to a significant
      extent, and the diffusion of water vapor will remain the rate-limiting step in
      the absence of gravity. Finally, the effects of several of the parameters, such
      as initial drop volume, drop-to-reservoir distance and temperature, are
      considered quantitatively. The equilibration rate was found to vary nearly
      linearly with drop volume. The equilibration rate decreases roughly by a factor
      of three as the temperature decreases from 293 to 276 K. This decrease in the
      equilibration rate is greater than would be expected when just considering the
      change in the diffusion coefficient of water vapor in air. This large dependence
      can, however, be attributed to the change in water-vapor pressure. Most
      surprisingly, a linear dependence on drop-to-reservoir distance is found, a
      result that agrees very well with experiment.

PMID- 10089463
TI  - Crystallization and X-ray diffraction data of a tRNASec acceptor-stem helix.
AB  - tRNASec is a UGA suppressor tRNA which co-translationally inserts selenocysteine
      into proteins. Its eight-base-pair tRNASec acceptor stem, which contains key
      recognition elements, was synthesized using solid-phase phosphoramidite RNA
      chemistry. High-resolution X-ray diffraction data were collected using
      synchrotron radiation under cryogenic cooling conditions. The crystals diffract
      to a maximal resolution of 1.8 A. X-ray diffraction data were processed to 2.4 A.
      tRNASec microhelix crystallizes in space group R32, with cell constants a =
      47.02, b = 47.02, c = 373.03 A, alpha = beta = 90, gamma = 120 degrees. The
      crystals contain three RNA molecules per asymmetric unit.

PMID- 10089464
TI  - Crystallization and preliminary X-ray diffraction studies of perchloric acid
      soluble protein (PSP) from rat liver.
AB  - Perchloric acid soluble protein purified from the cytosol fraction of rat liver
      has been crystallized in a form suitable for high-resolution X-ray diffraction
      studies. Octahedral crystals reaching 0.5 mm in cross-sectional diameter were
      produced by the hanging-drop method using polyethylene glycol (Mr = 8 kDa) as
      precipitant. These crystals diffract to 2.44 A on an in-house X-ray source and to
      1.8 A using a bending-magnet beamline at ESRF Grenoble. The crystals belong to
      the cubic space group P213 with a = 89.90 A and two molecules per asymmetric
      unit, as indicated from a Vm value of 2.12 A3 Da-1 and self-rotation function
      computation. Screening for heavy-atom derivatives identified a platinum compound
      and xenon that bind to the protein.

PMID- 10089465
TI  - Crystallization and preliminary X-ray analysis of human muscle creatine kinase.
AB  - Creatine kinase is a key enzyme in the energy homeostasis of cells and tissues
      with high and fluctuating energy demands. Human muscle MM creatine kinase is a
      dimeric protein with a molecular weight of approximately 43 kDa for each subunit.
      It has been crystallized by the hanging-drop vapor-diffusion method using 2
      methyl-2, 4-pentanediol as precipitant. The crystals belong to the
      enantiomorphous space group P6222 or P6422 with cell parameters of a = b = 89.11
      and c = 403.97 A. The asymmetric unit of the crystal contains two subunits. A
      data set at 3.3 A resolution has been collected using synchrotron radiation.

PMID- 10089466
TI  - Crystallization of the regulatory and effector domains of the key sporulation
      response regulator Spo0A.
AB  - The key response-regulator gene of sporulation, spo0A, has been cloned from
      Bacillus stearothermophilus and the encoded protein purified. The DNA-binding and
      phospho-acceptor domains of Spo0A have been prepared by tryptic digestion of the
      intact protein and subsequently crystallized in forms suitable for X-ray
      crystallographic studies. The DNA-binding domain has been crystallized in two
      forms, one of which diffracts X-rays to beyond 2. 5 A spacing. The crystals of
      the phospho-acceptor domain diffract X-rays beyond 2.0 A spacing using
      synchrotron radiation.

PMID- 10089467
TI  - Cloning, crystallization and preliminary X-ray analysis of a nucleotide-diphospho
      sugar transferase spsA from Bacillus subtilis.
AB  - Nucleotide-diphospho-sugar transferases represent, in terms of quantity, one of
      the most important groups of enzymes on Earth, yet little is known about their
      structure and mechanism. Such a transferase, the spsA gene product involved in
      the synthesis of the bacterial spore coat in Bacillus subtilis, has been cloned
      and over-expressed in an Escherichia coli expression system. Crystals have been
      grown, using PEG 8000 as a precipitant, in a form suitable for high-resolution X
      ray analysis. They belong to space group C2221, with unit-cell dimensions a =
      42.4, b = 142.0, c = 81.4 A and with one molecule of spsA in the asymmetric unit.
      The crystals diffract beyond 1.5 A using synchrotron radiation.

PMID- 10089468
TI  - Cloning, overexpression, crystallization and preliminary X-ray analysis of a
      family 1 beta--glucosidase from Streptomyces.
AB  - An intracellular beta-glucosidase (Bgl3) from Streptomyces sp. has been cloned
      and overexpressed in Escherichia coli. The introduction of a His tag at the N
      terminal end of the protein has allowed its purification to homogeneity by a
      single chromatographic step, with yields of 150-200 mg of pure protein per litre
      of E. coli culture. The enzyme (52.6 kDa) is a retaining glycosidase able to
      hydrolyze a wide range of disaccharides and oligosaccharides and to perform
      transglycosylation. Crystals of recombinant Bgl3 have been grown from an ammonium
      sulfate solution using the hanging-drop vapour-diffusion method at 293 K. The
      crystals belong to the orthorhombic space group I222 with unit-cell dimensions a
      = 101.6, b = 113.4 and c = 187.5 A at room temperature and contain two molecules
      per asymmetric unit. A full 1.69 A resolution diffraction data set (97.7%
      completeness) has been collected from frozen crystals in a solution containing
      30% sucrose, using synchrotron radiation.

PMID- 10089469
TI  - Crystallization and preliminary X-ray analysis of plastocyanin from
      cyanobacterium Synechococcus sp. PCC 7942.
AB  - A plastocyanin from the cyanobacterium Synechococcus sp. PCC 7942 has been
      crystallized in two different forms by hanging-drop vapour diffusion with
      ammonium sulfate as precipitant. Form I is hexagonal, space group P61 or P65,
      with unit-cell dimensions a = b = 34.62 and c = 107.22 A. Form II is tetragonal,
      space group P41 or P43, with unit-cell dimensions a = b = 43.05 and c = 56.94 A.
      Form I crystals diffract to 2.5 A using graphite-monochromated Cu Kalpha
      radiation from a Rigaku RU-300 rotating-anode generator operated at 40 kV and 100
      mA. Form II crystals diffract to 1.9 A using synchrotron radiation at beamline
      BL6A of the Photon Factory (KEK). Molecular-replacement calculations using the
      structure of plastocyanin from Ulva pertusa have been performed.

PMID- 10089470
TI  - Crystallization and preliminary X-ray diffraction studies of the
      lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6
      epimerase from Escherichia coli K-12.
AB  - ADP-L-glycero-D-mannoheptose 6-epimerase is a 240 kDa NAD-dependent nucleotide
      diphosphosugar epimerase from Escherichia coli K12 which catalyzes the
      interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose.
      ADP-L-glycero-D-mannoheptose is a required intermediate for lipopolysaccharide
      inner-core and outer-membrane biosynthesis in several genera of pathogenic and
      non-pathogenic Gram-negative bacteria. ADP-L-glycero-D-mannoheptose 6-epimerase
      was overexpressed in E. coli and purified to apparent homogeneity by
      chromatographic methods. Three crystal forms of the epimerase were obtained by a
      hanging-drop vapor-diffusion method. A native data set for crystal form III was
      collected in-house on a Rigaku R-AXIS-IIC image plate at 3.0 A resolution. The
      form III crystals belong to the monoclinic space group P21. The unit-cell
      parameters are a = 98.94, b = 110.53, c = 180.68 A and beta = 90.94 degrees. Our
      recent results show that these crystals diffract to 2.0 A resolution at the
      Cornell High Energy Synchrotron Source. The crystal probably contains six 40 kDa
      monomers per asymmetric unit, with a corresponding volume per protein mass (Vm)
      of 4.11 A3 Da-1 and a solvent fraction of 70%.

PMID- 10089471
TI  - Preliminary X-ray crystallographic analysis of a novel phytase from a Bacillus
      amyloliquefaciens strain.
AB  - A novel bacterial phytase from a Bacillus amyloliquefaciens strain was
      crystallized using the hanging-drop vapour-diffusion method. The amino-acid
      sequence of the enzyme does not show any homology to those of other known
      phytases or phosphatases, with the exception of a phytase from Bacillus subtilis.
      The enzyme exhibits a thermal stability which is strongly dependent on calcium
      ions. High-quality single crystals of the enzyme in the absence of calcium ions
      were obtained using a precipitant solution containing 20% 2-methyl-2, 4
      pentanediol and 0.1 M MES (pH 6.5). Native diffraction data to 2.0 A resolution
      were obtained from a flash-frozen crystal at 110 K using a rotating-anode X-ray
      source. The crystals belong to space group P212121 with unit-cell dimensions a =
      50.4, b = 64.1, c = 104. 2 A and contain one monomer per asymmetric unit.
      Structure determination using heavy-atom derivative crystals is in progress,
      along with an effort to crystallize the calcium ion bound form of the enzyme.

PMID- 10089472
TI  - Expression, crystallization and preliminary X-ray diffraction studies of N
      carbamyl-D-amino-acid amidohydrolase from Agrobacterium radiobacter.
AB  - The Agrobacterium radiobacter CCRC 14924 N-carbamyl-D-amino-acid amidohydrolase,
      the enzyme used for production of D-amino acids, was overexpressed in Escherichia
      coli JM109. The expressed protein was crystallized by vapour diffusion using
      lithium sulfate as precipitant. It crystallizes in space group P21 with unit-cell
      parameters a = 69.8, b = 67.9 and c = 137.8 A and beta = 96.4 degrees. There are
      four molecules per asymmetric unit. Crystals diffract to 2.8 A resolution using a
      rotating-anode source at cryogenic (113 K) temperatures.

PMID- 10089473
TI  - Crystallization and preliminary X-ray analysis of tryparedoxin I from Crithidia
      fasciculata.
AB  - The thioredoxin-related protein tryparedoxin I from Crithidia fasciculata has
      been crystallized using PEG 4000 as a precipitant. The enzyme forms long needle
      shaped crystals which diffract to at least 1.7 A. A native data set has been
      collected at the DESY synchrotron from a flash-frozen crystal at 90 K to 1.7 A
      resolution. The data set shows that the crystals belong to the orthorhombic space
      group P212121 and have unit-cell parameters a = 37.94, b = 51. 39, c = 71.46 A.
      Tryparedoxin I is involved in a trypanothione-dependent peroxide metabolic
      pathway specific for trypanosomatids and may therefore be a suitable candidate
      for the design of drugs for the specific treatment of a variety of important
      tropical diseases caused by these parasites.

PMID- 10089474
TI  - Crystallization and preliminary X-ray analysis of a new L-aminopeptidase-D
      amidase/D-esterase activated by a Gly-Ser peptide bond hydrolysis.
AB  - Ochrobactrum anthropi possesses an L-aminopeptidase (DmpA) also able to act as a
      D-amidase/D-esterase. DmpA (40 kDa) is activated by auto-catalyzed protein
      splicing liberating an alpha-amino group presumably used as a general base in the
      catalytic mechanism. Two crystal forms were obtained at 294 K in 13-16% PEG 2000
      mono-methylether at pH 9.0, adding either 0.2 M magnesium chloride or 1 M lithium
      chloride. Crystals of the first form belong to the space group C2221 and diffract
      to 3.0 A resolution, whereas crystals of the second form belong to the space
      group P21212 and diffract to 2.3 A resolution. Initial screening for heavy-atom
      derivatives on form II crystals, has led to a well substituted Hg derivative.

PMID- 10089475
TI  - Crystallization and preliminary X-ray diffraction studies of pyrrolidone carboxyl
      peptidase from the hyperthermophilic archaeon Thermococcus litoralis.
AB  - Pyrrolidone carboxyl peptidase from the hyperthermophilic archaeon Thermococcus
      litoralis has been crystallized in a form suitable for X-ray diffraction from
      ammonium sulfate or ammonium dihydrogen orthophosphate using the vapour-phase
      diffusion method. Crystals from both precipitants are of the orthorhombic space
      group P21212 with unit-cell dimensions a = 94.06, b = 149.06, c = 73.54 A. A
      complete data set to 2.8 A resolution has been collected from crystals grown from
      ammonium sulfate.

PMID- 10089476
TI  - Crystallization and preliminary X-ray diffraction studies of a DNA excision
      repair enzyme, UvrB, from Thermus thermophilus HB8.
AB  - A DNA excision repair enzyme, UvrB, from Thermus thermophilus HB8 was
      crystallized by the vapor-diffusion method using lithium sulfate as the
      precipitant and beta-octylglucoside as an additive. The crystals belong to the
      trigonal space group P3121 or P3221, with unit-cell dimensions of a = b = 136.0
      and c = 108.1 A. The crystal is most likely to contain one UvrB protein in an
      asymmetric unit with the Vm value of 3.8 A3 Da-1. The crystals diffracted X-rays
      beyond 2.9 A resolution. Although the crystals were sensitive to X-ray
      irradiation at room temperature, the frozen crystals at 100 K showed no apparent
      decay during the intensity measurement.

PMID- 10089477
TI  - A fully functional deletion staphylokinase derivative crystallizes in two non
      isomorphous monoclinic modifications.
AB  - Two non-isomorphous monoclinic types of diffraction-quality crystals of
      Delta10Sak, a fully functional staphylokinase derivative lacking the first ten
      amino acids, have been grown by the hanging-drop vapour-diffusion technique. Type
      I crystals grow from a solution containing Zn(OAc)2, Tris buffer pH 7.5 and PEG
      8000, while type II crystals can be obtained from a solution containing MgCl2,
      Tris buffer pH 8.5 and PEG 4000. Both crystal types were suitable for data
      collection (to 2.4 and 2.6 A resolution, respectively) and further structural
      investigation.

PMID- 10089478
TI  - Preliminary characterization by X-ray diffraction and Raman spectroscopy of a
      crystalline complex of Bacillus stearothermophilus initiation factor 2 C-domain
      and fMet-tRNAfMet.
AB  - Bacillus stearothermophilus translation initiation factor 2 (IF2) specifically
      binds initiator fMet-tRNAfMet and positions it into the ribosomal peptidyl site
      in the course of the initiation of protein biosynthesis. The isolated C-terminal
      domain of IF2 is capable of binding fMet-tRNAfMet, as shown by RNase A and
      hydrolysis protection experiments. In the presence of fMet-tRNAfMet, the IF2 C
      domain yielded orthorhombic crystals of space group I222 (I212121) diffracting to
      3.4 A resolution. The existence of equimolar amounts of tRNA and protein in the
      crystals was proven by Raman spectroscopy. The observed unit cell suggests the
      presence of two IF2 C- domain-fMet-tRNAfMet complexes per asymmetric unit of the
      crystal.

PMID- 10089479
TI  - Separation and crystallization of T = 3 and T = 4 icosahedral complexes of the
      hepatitis B virus core protein.
AB  - The icosahedral nucleocapsid of human hepatitis B virus is a homopolymer of the
      dimeric capsid protein also known as hepatitis B core antigen or HBcAg. Purified
      capsid protein obtained from an Escherichia coli expression system was
      reassembled into a mixture of T = 3 and T = 4 icosahedral particles consisting of
      90 and 120 dimers, respectively. The two types of capsid were separated on a
      preparative scale by centrifugation through a sucrose gradient. In addition to
      this heterogeneity, the capsid protein has three cysteines, one of which has a
      great propensity for forming disulfide bonds between the two subunits, forming a
      dimer. To eliminate heterogeneity arising from oxidation, alanines were
      substituted for the cysteines. T = 3 and T = 4 capsids crystallized under similar
      conditions. Crystals of T = 3 capsids diffracted to approximately 8 A resolution;
      crystals of T = 4 capsids diffracted to 4 A resolution.

PMID- 10089480
TI  - Production of crystals of human aldose reductase with very high resolution
      diffraction.
AB  - As the action of human aldose reductase (hAR) is thought to be linked to the
      pathogenesis of diabetic complications, much effort has been directed towards the
      analysis of the catalytic mechanism and the development of specific inhibitors.
      Here, the crystallization of recombinant hAR with its cofactor NADP+ at 277 K in
      the presence of the precipitating agent PEG 6000 is reported. The crystals
      diffract to high resolution (1.1 A) and belong to the P21 space group with unit
      cell parameters a = 49.97, b = 67.14, c = 48. 02 A, beta = 92.2 degrees with one
      molecule per asymmetric unit. Seleno-substituted hAR crystals were also produced
      and diffract to 1. 7 A on a conventional X-ray source.

PMID- 10089481
TI  - The globalization of crystallographic knowledge.
AB  - The rapid growth of the World Wide Web provides major new opportunities for
      distributed databases, especially in macromolecular science. A new generation of
      technology, based on structured documents (SD), is being developed which will
      integrate documents and data in a seamless manner. This offers experimentalists
      the chance to publish and archive high-quality data from any discipline. Data and
      documents from different disciplines can be combined and searched using
      technology such as eXtensible Markup Language (XML) and its associated support
      for hypermedia (XLL), metadata (RDF) and stylesheets (XSL). Opportunities in
      crystallography and related disciplines are described.

PMID- 10089482
TI  - Iditis: protein structure database.
AB  - The validation, enrichment and organization of the data stored in PDB files is
      essential for those data to be used accurately and efficiently for modelling,
      experimental design and the determination of molecular interactions. The Iditis
      protein structure database has been designed to allow the widest possible range
      of queries to be performed across all available protein structures. The Iditis
      database is the most comprehensive protein structure resource currently
      available, and contains over 500 fields of information describing all publicly
      deposited protein structures. A custom-written database engine and graphical user
      interface provide a natural and simple environment for the construction of
      searches for complex sequence- and structure-based motifs. Extensions and
      specialized interfaces allow the data generated by the database to used in
      conjunction with a wide range of applications.

PMID- 10089483
TI  - Protein Data Bank (PDB): database of three-dimensional structural information of
      biological macromolecules.
AB  - The Protein Data Bank (PDB) at Brookhaven National Laboratory, is a database
      containing experimentally determined three-dimensional structures of proteins,
      nucleic acids and other biological macromolecules, with approximately 8000
      entries. Data are easily submitted via PDB's WWW-based tool AutoDep, in either
      mmCIF or PDB format, and are most conveniently examined via PDB's WWW-based tool
      3DB Browser.

PMID- 10089484
TI  - Macromolecular structure databases: past progress and future challenges.
AB  - Databases containing macromolecular structure data provide a crystallographer
      with important tools for use in solving, refining and understanding the
      functional significance of their protein structures. Given this importance, this
      paper briefly summarizes past progress by outlining the features of the
      significant number of relevant databases developed to date. One recent database,
      PDB+, containing all current and obsolete structures deposited with the Protein
      Data Bank (PDB) is discussed in more detail. PDB+ has been used to analyze the
      self-consistency of the current (1 January 1998) corpus of over 7000 structures.
      A summary of those findings is presented (a full discussion will appear
      elsewhere) in the form of global and temporal trends within the data. These
      trends indicate that challenges exist if crystallographers are to provide the
      community with complete and consistent structural results in the future. It is
      argued that better information management practices are required to meet these
      challenges.

PMID- 10089485
TI  - The Nucleic Acid Database: A resource for nucleic acid science.
AB  - The Nucleic Acid Database (NDB) distributes information about nucleic acid
      containing structures. Here the information content of the database as well as
      the query capabilities are described. A summary of how the technology developed
      by this project has been used to develop other macromolecular databases is given.

PMID- 10089486
TI  - Deposition of macromolecular structures.
AB  - Macromolecular structures are being determined at an increasing rate, and are of
      interest to a wide diversity of researchers. Depositing a macromolecular
      structure with the Protein Data Bank makes it readily available to the community.
      Accuracy, consistency and machine-readability of the data are essential, as are
      clear indications of quality, and sufficient information to allow non
      experimentalists to interpret the data. Good-quality depositions are necessary to
      allow this to be achieved. The PDB's AutoDep system allows deposition and some
      preliminary automatic checking to take place at multiple sites, prior to full
      processing and release of the structure by the PDB. However, depositing a
      structure currently requires the manual entry of a large amount of information at
      the time of deposition. The data-harvesting approach will allow much more
      information to be deposited, without placing an additional burden on the
      depositor. Deposition-ready files will be generated automatically during the
      course of a structure-determination experiment. The additional information will
      allow improved validation procedures to be applied to the structures, and the
      data to be made more useful to the wider scientific community.

PMID- 10089487
TI  - The role of validation in macromolecular crystallography.
AB  - The importance of validation techniques in X-ray structure determination and
      their relation to refinement procedures are discussed, with particular reference
      to atomic resolution structures. The requirements of deposition and publication,
      and the role of validation tools in this are analysed. The need for a rigorously
      defined file format is emphasized.

PMID- 10089488
TI  - Databases in protein crystallography.
AB  - Applications of structural databases in the protein crystallographic structure
      determination process are reviewed, using mostly examples from work carried out
      by the authors. Four application areas are discussed: model building, model
      refinement, model validation and model analysis.

PMID- 10089489
TI  - New tools and resources for analysing protein structures and their interactions.
AB  - The determination of protein structures has furthered our understanding of how
      various proteins perform their functions. With the large number of structures
      currently available in the PDB, it is necessary to be able to easily study these
      proteins in detail. Here new software tools are presented which aim to facilitate
      this analysis; these include the PDBsum WWW site which provides a summary
      description of all PDB entries, the programs TOPS and NUCPLOT to plot schematic
      diagrams representing protein topology and DNA-binding interactions, SAS a WWW
      based sequence-analysis tool incorporating structural data, and WWW servers for
      the analysis of protein-protein interfaces and analyses of over 300 haem-binding
      proteins.

PMID- 10089490
TI  - Protein sequence alignment techniques.
AB  - The basic algorithms for alignment of two or more protein sequences are
      explained. Alternative methods for scoring substitutions and gaps (insertions and
      deletions) are described, as are global and local alignment methods. Multiple
      alignment techniques are explained, including methods for profile comparison. A
      summary is given of programs for the alignment and analysis of protein sequences,
      either from sequence alone, or from three-dimensional structure.

PMID- 10089491
TI  - SCOP, Structural Classification of Proteins database: applications to evaluation
      of the effectiveness of sequence alignment methods and statistics of protein
      structural data.
AB  - The Structural Classification of Proteins (SCOP) database provides a detailed and
      comprehensive description of the relationships of all known protein structures.
      The classification is on hierarchical levels: the first two levels, family and
      superfamily, describe near and far evolutionary relationships; the third, fold,
      describes geometrical relationships. The distinction between evolutionary
      relationships and those that arise from the physics and chemistry of proteins is
      a feature that is unique to this database, so far. The database can be used as a
      source of data to calibrate sequence search algorithms and for the generation of
      population statistics on protein structures. The database and its associated
      files are freely accessible from a number of WWW sites mirrored from URL
      http://scop. mrc-lmb.cam.ac.uk/scop/.

PMID- 10089492
TI  - Classifying a protein in the CATH database of domain structures.
AB  - The CATH database of protein domain structures classifies structures according to
      their (C)lass, (A)rchitecture, (T)opology or fold and (H)omologous family
      (http://www.biochem.ucl.ac.uk/bsm/cath). Although the protocol used is mostly
      automatic, manual inspection is used to check assignments at some critical
      stages, such as the detection of very distantly related homologues and anologues
      and the assignment of novel architectures. Described in this article is a
      recently established facility to search the database with the coordinates of a
      newly determined structure. The CATH server first locates domain boundaries and
      then uses automatic sequence and structure comparison methods to assign this new
      structure to one or more of the domain families within CATH. Diagnostic reports
      are generated, together with multiple structural alignments for close relatives.
      The Server can be accessed over the World Wide Web (WWW) and mirror sites are
      planned to improve access.

PMID- 10089493
TI  - Protein three-dimensional structural databases: domains, structurally aligned
      homologues and superfamilies.
AB  - This paper reports the availability of a database of protein structural domains
      (DDBASE), an alignment database of homologous proteins (HOMSTRAD) and a database
      of structurally aligned superfamilies (CAMPASS) on the World Wide Web (WWW).
      DDBASE contains information on the organization of structural domains and their
      boundaries; it includes only one representative domain from each of the
      homologous families. This database has been derived by identifying the presence
      of structural domains in proteins on the basis of inter-secondary structural
      distances using the program DIAL [Sowdhamini & Blundell (1995), Protein Sci. 4,
      506-520]. The alignment of proteins in superfamilies has been performed on the
      basis of the structural features and relationships of individual residues using
      the program COMPARER [Sali & Blundell (1990), J. Mol. Biol. 212, 403-428]. The
      alignment databases contain information on the conserved structural features in
      homologous proteins and those belonging to superfamilies. Available data include
      the sequence alignments in structure-annotated formats and the provision for
      viewing superposed structures of proteins using a graphical interface. Such
      information, which is freely accessible on the WWW, should be of value to
      crystallographers in the comparison of newly determined protein structures with
      previously identified protein domains or existing families.

PMID- 10089494
TI  - Databases for protein-ligand complexes.
AB  - Recent advances in experimental techniques have led to an enormous explosion of
      available data about protein-ligand complexes. To exploit the information that is
      hidden in these large data, collection tools for managing and accessing huge data
      collections are needed. This paper discusses databases for protein-ligand data
      which are accessible via the World Wide Web. A strong focus is placed on the
      ReLiBase database system which is a new three-dimensional database for storing
      and analysing structures of protein-ligand complexes currently deposited in the
      Brookhaven Protein Data Bank (PDB). ReLiBase contains efficient query tools for
      identifying and analysing ligands and protein-ligand complexes. Its application
      for structure-based drug design is illustrated.

PMID- 10089495
TI  - Directional preferences of intermolecular contacts to hydrophobic groups.
AB  - Analysis of data from the IsoStar library shows that many hydrophobic groups
      exhibit strikingly strong directional preferences in their intermolecular
      interactions. Specific directional interactions may occur because of the large
      quadrupole moments of many aromatic ring systems, the residual electropositive
      charge on most carbon-bound H atoms and the effects of polarization on soft
      hetero-ring atoms such as sulfur. In consequence, the binding of a hydrophobic
      group to a hydrophobic protein cavity is not simply a matter of matching
      complementary shapes. Directional preferences of nonbonded contacts to
      hydrophobic groups may need to be taken into account in parameterizing the next
      generation of protein-ligand docking programs.

PMID- 10089496
TI  - Metal complex geometries in small-molecule crystals.
AB  - The origins, scope and utility of compilations of metal-ligand and intraligand
      bond lengths based on the Cambridge Structural Database are discussed. The
      limitations on the apparent uncertainty of metal-ligand bond lengths derived from
      crystallographic data and recent evidence of metal-assisted hydrogen bonding
      involving ligands are reviewed in the light of the transferability of bond-length
      values from one crystal structure determination.

PMID- 10089497
TI  - HAD, a data bank of heavy-atom binding sites in protein crystals: a resource for
      use in multiple isomorphous replacement and anomalous scattering.
AB  - Information on the preparation and characterization of heavy-atom derivatives of
      protein crystals has been collected, either from the literature or directly from
      protein crystallographers, and assembled in the form of a heavy-atom data bank
      (HAD). The data bank contains coordinate data for the heavy-atom positions in a
      form that is compatible with the crystallographic data in the Brookhaven Protein
      Data Bank, together with a wealth of information on the crystallization
      conditions, the nature of the heavy-atom reagent and references to relevant
      publications. Some statistical information derived from the data bank, such as
      the most popular heavy-atom derivatives, is also included. The information can be
      directly accessed and should be useful to protein crystallographers seeking to
      improve their success in preparing heavy-atom derivatives for the methods of
      isomorphous replacement and anomalous dispersion. The World Wide Web address of
      HAD is http://www.icnet.uk/bmm/had.

PMID- 10089498
TI  - Structure of the E2 DNA-binding domain from human papillomavirus serotype 31 at
      2.4 A.
AB  - The papillomaviruses are a family of small double-stranded DNA viruses which
      exclusively infect epithelial cells and stimulate the proliferation of those
      cells. A key protein within the papillomavirus life-cycle is known as the E2
      (Early 2) protein and is responsible for regulating viral transcription from all
      viral promoters as well as for replication of the papillomavirus genome in tandem
      with another protein known as E1. The E2 protein itself consists of three
      functional domains: an N-terminal trans-activation domain, a proline-rich linker,
      and a C-terminal DNA-binding domain. The first crystal structure of the human
      papillomavirus, serotype 31 (HPV-31), E2 DNA-binding domain has been determined
      at 2.4 A resolution. The HPV DNA-binding domain monomer consists of two beta
      alpha-beta repeats of approximately equal length and is arranged as to have an
      anti-parallel beta-sheet flanked by the two alpha-helices. The monomers form the
      functional in vivo dimer by association of the beta-sheets of each monomer so as
      to form an eight-stranded anti-parallel beta-barrel at the center of the dimer,
      with the alpha-helices lining the outside of the barrel. The overall structure of
      HVP-31 E2 DNA-binding domain is similar to both the bovine papillomavirus E2
      binding domain and the Epstein-Barr nuclear antigen-1 DNA-binding domain.

PMID- 10089499
TI  - Biochemical and crystallographic characterization of homologous non-peptidic
      thrombin inhibitors having alternate binding modes.
AB  - The X-ray crystallographic structure of [N-(3-phenylpropionyl)-N-(phenethyl)]-Gly
      boroLys-OH (HPBK, Ki = 0. 42 nM, crystallographic R factor to 1.8 A resolution,
      19.6%) complexed with human alpha-thrombin shows that the boron adopts a
      tetrahedral geometry and is covalently bonded to the active serine, Ser195. The
      HPBK phenethyl aromatic ring forms an edge-to-face interaction with the indole
      side chain of Trp215. Four HPBK analogs containing either electron-withdrawing or
      electron-donating substitutents at the 3' position of the phenethyl ring were
      synthesized in an attempt to modulate ligand affinity by inductive stabilization
      of the edge-to-face interaction. Refined crystallographic structures of the
      trifluoromethyl (Ki = 0.37 nM, crystallographic R factor to 2.0 A resolution =
      18.7%), fluoro (Ki = 0.60; R factor to 2.3 A resolution = 18.4%), methoxy (Ki =
      0.91 nM, R factor to 2.2 A resolution = 19.8%) and methyl (Ki = 0.20 nM, R factor
      to 2.5 A resolution = 16.9%) HPBK analogs complexed with thrombin revealed two
      binding modes for the closely related compounds. A less than 1.5-fold variation
      in affinity was observed for analogs (trifluoromethyl-HPBK and fluoro-HPBK)
      binding with the edge-to-face interaction. The slight inductive modulation is
      consistent with the overall weak nature of the edge-to-face interaction. Owing to
      an unexpected rotation of the phenethyl aromatic ring, the 3' substituent of two
      analogs, methoxy-HPBK and methyl-HPBK, made direct contact with the Trp215 indole
      side chain. Increased affinity of the 3' methyl analog is attributed to favorable
      interactions between the methyl group and the Trp215 indole ring. Differences in
      inhibitor, thrombin and solvent structure are discussed in detail. These results
      demonstrate the subtle interplay of weak forces that determine the equilibrium
      binding orientation of inhibitor, solvent and protein.

PMID- 10089500
TI  - Polarized Raman spectroscopic studies of tetragonal lysozyme single crystals.
AB  - Polarized Raman spectra have been obtained for tetragonal lysozyme single
      crystals of different relative quality. The Raman band at 507 cm-1, which
      corresponds to the totally symmetric stretch vibration of the gauche-gauche
      gauche (ggg) disulfide bridges of the protein, has been shown to possess
      different polarization characteristics compared with the gauche-gauche-trans
      (ggt) disulfide bridge band at 528 cm-1. The relative intensities of the ggg and
      ggt bands in the polarized Raman spectra have been numerically estimated for a
      number of tetragonal lysozyme single crystals, the X-ray diffraction data of
      which are available from the Protein Data Bank. On the basis of comparison
      between the experimental and calculated polarization characteristics of the
      disulfide Raman lines, the following main conclusions have been drawn. The
      orientation of the protein molecules correlates with the average orientation of
      their ggg disulfide bridges. This in turn can be described by the rhoggg value
      which reflects the average orientation of the S-S bonds with respect to the Z
      crystallographic axis and can be determined from polarized Raman spectra.
      Crystals of better quality are characterized by a better alignment of the protein
      molecules with respect to the Z axis, a smaller perturbation of the protein
      molecules in the crystal lattice and a somewhat higher interlattice water
      content.

PMID- 10089501
TI  - The two-dimensional histogram as a constraint for protein phase improvement.
AB  - The joint distribution of electron density and its gradient in a protein electron
      density map was examined. This joint distribution was represented by a two
      dimensional histogram (2D histogram) of electron-density values and the modulus
      of the gradient. 16 structures representing distinct protein-fold families were
      selected to study the dependence of the 2D histogram on resolution, overall
      temperature factor, structural conformation and phase error. The similarity
      between the histograms for a pair of structures was measured by correlation
      coefficient, and the residual provided a measure of the difference. The 2D
      histogram was found to vary with resolution and overall temperature factor, but
      was found to be insensitive to structure conformation. The average correlation
      coefficient between pairs of 2D histograms at three different resolutions
      examined was 0.90 with a standard deviation of 0.04. The average residual for the
      same condition was 0.13 with a standard deviation of 0.03. The 2D histogram was
      also found to be sensitive to phase error. The average correlation coefficient
      and residual between 2D histograms with 10 degrees phase difference are 0.71 and
      0.18, respectively. The variation of the 2D histogram resulting from structure
      conformation changes was estimated to be equivalent to that of a 4 degrees phase
      error. This establishes the minimal phase error that a 2D histogram-matching
      method could achieve. The conservation of the 2D histogram with respect to
      structure conformation enables the prediction of the ideal 2D histogram for
      unknown structures. The sensitivity of the 2D histogram to phase error suggests
      that it could be used as a target for the density-modification method and also
      could be used as a figure of merit for phase selection in ab initio phasing.

PMID- 10089502
TI  - Structural parameters for proteins derived from the atomic resolution (1.09 A)
      structure of a designed variant of the ColE1 ROP protein.
AB  - The crystal structure of a designed variant of the ColE1 repressor of primer
      (ROP) protein has been refined with SHELXL93 to a resolution of 1.09 A. The final
      model with 510 non-H protein atoms, 576 H atoms in calculated positions and 114
      water molecules converged to a standard R factor of 10% using unrestrained
      blocked full-matrix refinement. For all non-H atoms six-parameter anisotropic
      thermal parameters have been refined. The majority of atomic vibrations have a
      preferred orientation which is approximately perpendicular to the bundle axis;
      analysis with the TLS method [Schomaker & Trueblood (1968). Acta Cryst. B24, 63
      77] showed a relatively good agreement between the individual atomic
      displacements and a rigid-body motion of the protein. Disordered residues with
      multiple conformations form clusters on the surface of the protein; six C
      terminal residues have been omitted from the refined model due to disorder. Part
      of the solvent structure forms pentagonal or hexagonal clusters which bridge
      neighbouring protein molecules. Some water molecules are also conserved in wild
      type ROP. The unrestrained blocked full-matrix least-squares refinement yielded
      reliable estimates of the standard deviations of the refined parameters.
      Comparison of these parameters with the stereochemical restraints used in various
      protein refinement programs showed statistically significant differences. These
      restraints should be adapted to the refinement of macromolecules by taking into
      account parameters determined from atomic resolution protein structures.

PMID- 10089503
TI  - Structure determination of echovirus 1.
AB  - The atomic structure of echovirus 1 (a member of the enterovirus genus of the
      picornavirus family) has been determined using cryo-crystallography and refined
      to 3.55 A resolution. Echovirus 1 crystallizes in space group P22121 with a =
      352.45, b = 472.15 and c = 483.20 A. The crystals contain one full virus particle
      in the asymmetric unit allowing for 60-fold noncrystallographic symmetry
      averaging. The diffraction pattern shows strong pseudo-B-centering with
      reflections with h + l = 2n + 1 being systematically weak or absent below about 6
      A resolution. The size of the unit cell and presence of pseudo-B-centering placed
      strong constraints on the allowed packing of the icosahedral particle in the
      crystal lattice. These constraints greatly facilitated the determination of the
      orientation and position of the virus by reducing the dimensionality of the
      search, but interactions between the crystallographic and noncrystallographic
      symmetries rendered the choice of space group ambiguous until very late in the
      structure determination. This structure determination provides a striking example
      of the power of packing analysis in molecular replacement and illustrates how
      subtle interactions between crystallographic and noncrystallographic symmetries
      can be resolved.

PMID- 10089504
TI  - Structure of d(TGCGCA)2 and a comparison to other DNA hexamers.
AB  - The X-ray crystal structure of d(TGCGCA)2 has been determined at 120 K to a
      resolution of 1.3 A. Hexamer duplexes, in the Z-DNA conformation, pack in an
      arrangement similar to the 'pure spermine form' [Egli et al. (1991).
      Biochemistry, 30, 11388-11402] but with significantly different cell dimensions.
      The phosphate backbone exists in two equally populated discrete conformations at
      one nucleotide step, around phosphate 11. The structure contains two ordered
      cobalt hexammine molecules which have roles in stabilization of both the Z-DNA
      conformation of the duplex and in crystal packing. A comparison of d(TGCGCA)2
      with other Z-DNA hexamer structures available in the Nucleic Acid Database
      illustrates the elusive nature of crystal packing. A review of the interactions
      with the metal cations Na+, Mg2+ and Co3+ reveals a relatively small proportion
      of phosphate binding and that close contacts between metal ions are common. A
      prediction of the water structure is compared with the observed pattern in the
      reported structure.

PMID- 10089505
TI  - Incorporation of prior phase information strengthens maximum-likelihood structure
      refinement.
AB  - The application of a maximum-likelihood analysis to the problem of structure
      refinement has led to striking improvements over the traditional least-squares
      methods. Since the method of maximum likelihood allows for a rational
      incorporation of other sources of information, we have derived a likelihood
      function that incorporates experimentally determined phase information. In a
      number of different test cases, this target function performs better than either
      a least-squares target or a maximum-likelihood function lacking prior phases.
      Furthermore, this target gives significantly better results compared with other
      functions incorporating phase information. When combined with a procedure to mask
      'unexplained' density, the phased likelihood target also makes it possible to
      refine very incomplete models.

PMID- 10089506
TI  - Structure determination of Nudaurelia capensis omega virus.
AB  - The structure of Nudaurelia capensis omega virus (NomegaV), a single-stranded RNA
      virus, was determined to 2.8 A resolution. Triclinic crystals (a = 413.6, b =
      410.2, c = 419.7 A, alpha = 59.13, beta = 58.9, gamma = 64.0 degrees ) diffracted
      X-rays beyond 2.7 A resolution. The unit cell contained one icosahedral virus
      particle, providing 60-fold non-crystallographic symmetry (n.c.s.) and structural
      redundancy. The particle orientation in the unit cell was determined by self
      rotation function analyses. Initial phases to 18 A resolution were derived from a
      hollow spherical model of 192 A outer radius and 139 A inner radius, filled with
      uniform electron density. Radii of the model were determined by maximizing the
      correlation of the model-based calculated data with the low-resolution X-ray
      diffraction and solution-scattering data. Phases were refined by 60-fold non
      crystallographic electron-density averaging and extended in small steps to a
      resolution of 5 A. The phases obtained represented a mixture of four different
      phase sets, each consistent with the icosahedral symmetry constraints. The
      resulting electron density was not interpretable. A difference Fourier map
      computed with the native and an isomorphous heavy-atom derivative data sets and
      phases refined by real-space averaging was interpretable only if data within the
      10 A resolution shell were used. Maps calculated with data significantly higher
      than 10 A resolution failed to display a constellation of heavy-atom sites
      consistent with the T = 4 icosahedral symmetry. Attempts to extend the phases
      beyond 10 A resolution, starting with either phases based on a model or single
      isomorphous replacement, were unsuccessful. Successful phase extension was
      achieved by computing the phases for the higher resolution reflections from a
      partial atomic model (poly gly) built into the averaged 10 A electron-density
      map. Phases from this model served as the starting point for n.c.s. phase
      refinement and extension to slightly higher resolution. The atomic model was
      improved at each extension interval and these phases were used for the subsequent
      phase calculation and extension. The entire polypeptide backbone corresponding to
      the NomegaV structure was built into the map at 4 A. The same procedure for phase
      refinement was used to extend the phases to 2.8 A in small increments of
      resolution. The overall molecular averaging R factor and correlation coefficient
      at 2.8 A resolution were 18.4% and 0.87, respectively.

PMID- 10089507
TI  - Transferability of multipole charge-density parameters: application to very high
      resolution oligopeptide and protein structures.
AB  - Crystallography at sub-atomic resolution permits the observation and measurement
      of the non-spherical character of the electron density (parameterized as
      multipoles) and of the atomic charges. This fine description of the electron
      density can be extended to structures of lower resolution by applying the notion
      of transferability of the charge and multipole parameters. A database of such
      parameters has been built from charge-density analysis of several peptide
      crystals. The aim of this study is to assess for which X-ray structures the
      application of transferability is physically meaningful. The charge-density
      multipole parameters have been transferred and the X-ray structure of a 310 helix
      octapeptide Ac-Aib2-L-Lys(Bz)-Aib2-L-Lys(Bz)-Aib2-NHMe refined subsequently, for
      which diffraction data have been collected to a resolution of 0.82 A at a
      cryogenic temperature of 100 K. The multipoles transfer resulted in a significant
      improvement of the crystallographic residual factors wR and wR free. The
      accumulation of electrons in the covalent bonds and oxygen lone pairs is clearly
      visible in the deformation electron-density maps at its expected value. The
      refinement of the charges for nine different atom types led to an additional
      improvement of the R factor and the refined charges are in good agreement with
      those of the AMBER molecular modelling dictionary. The use of scattering factors
      calculated from average results of charge-density work gives a negligible shift
      of the atomic coordinates in the octapeptide but induces a significant change in
      the temperature factors (DeltaB approximately 0.4 A2). Under the spherical atom
      approximation, the temperature factors are biased as they partly model the
      deformation electron density. The transfer of the multipoles thus improves the
      physical meaning of the thermal-displacement parameters. The contribution to the
      diffraction of the different components of the electron density has also been
      analyzed. This analysis indicates that the electron-density peaks are well
      defined in the dynamic deformation maps when the thermal motion of the atoms is
      moderate (B typically lower than 4 A2). In this case, a non-truncated Fourier
      synthesis of the deformation density requires that the diffraction data are
      available to a resolution better than 0.9 A.

PMID- 10089508
TI  - Structure of human apolactoferrin at 2.0 A resolution. Refinement and analysis of
      ligand-induced conformational change.
AB  - The three-dimensional structure of a form of human apolactoferrin, in which one
      lobe (the N-lobe) has an open conformation and the other lobe (the C-lobe) is
      closed, has been refined at 2.0 A resolution. The refinement, by restrained least
      squares methods, used synchrotron radiation X-ray diffraction data combined with
      a lower resolution diffractometer data set. The final refined model (5346 protein
      atoms from residues 1-691, two Cl- ions and 363 water molecules) gives a
      crystallographic R factor of 0.201 (Rfree = 0. 286) for all 51305 reflections in
      the resolution range 10.0-2.0 A. The conformational change in the N-lobe, which
      opens up the binding cleft, involves a 54 degrees rotation of the N2 domain
      relative to the N1 domain. This also results in a small reorientation of the two
      lobes relative to one another with a further approximately 730 A2 of surface area
      being buried as the N2 domain contacts the C-lobe and the inter-lobe helix. These
      new contacts also involve the C-terminal helix and provide a mechanism through
      which the conformational and iron-binding status of the N-lobe can be signalled
      to the C-lobe. Surface-area calculations indicate a fine balance between open and
      closed forms of lactoferrin, which both have essentially the same solvent
      accessible surface. Chloride ions are bound in the anion-binding sites of both
      lobes, emphasizing the functional significance of these sites. The closed
      configuration of the C-lobe, attributed in part to weak stabilization by crystal
      packing interactions, has important implications for lactoferrin dynamics. It
      shows that a stable closed structure, essentially identical to that of the iron
      bound form, can be formed in the absence of iron binding.

PMID- 10089509
TI  - Molecular replacement: the revival of the molecular Fourier transform method.
AB  - The molecular Fourier transform method, perhaps the first application of the
      molecular-replacement approach, used in the 1950s for the two-dimensional
      structure determination of small molecules, has been modernised for the efficient
      solution of complex structures. In the modern application of the molecular
      Fourier transform (MFT), the three-dimensional transform of the molecular model
      is calculated and fitting is achieved by rotating the weighted reciprocal lattice
      with respect to the calculated transform. The fit between the transform and the
      weighted reciprocal lattice is gauged by three different criteria corresponding
      to R factor, correlation coefficient and product function. Since the procedure
      involves the rotation of indices and is, therefore, independent of the number of
      atoms, it is much faster than other methods which employ the rotation of the
      molecular model. This feature enabled the renovation of the rotation-translation
      search method ULTIMA, which utilizes low-order data and packing considerations
      for the efficient solution of large structures.

PMID- 10089510
TI  - Plasticity, hydration and accessibility in ribonuclease A. The structure of a new
      crystal form and its low-humidity variant.
AB  - The structures of a new crystal form of ribonuclease A and its low-humidity
      variant, each containing two crystallographically independent molecules, have
      been determined and refined. A detailed comparison of these structures with those
      of the other known crystal forms of the enzyme, which have different packing
      arrangements and solvent composition, leads to a meaningful delineation of the
      rigid and flexible regions of the protein molecule and the nature of its
      plasticity. Many of the water molecules which are common to all the structures
      are involved in bridging different regions of the protein molecule, thus
      emphasizing the role of water in stabilizing the tertiary structure. The analysis
      of the structures shows that for a given N or O atom, the level of hydration
      increases with accessible surface area, but levels off at an area of about 10 A2.
      Generally, the hydration level tends to drop when the area increases beyond about
      20 A2. This drop correlates with an increase in the displacement parameter. The
      analysis also suggests that the van der Waals radii and probe radius normally
      used in accessible surface area calculations are not appropriate for dealing with
      all situations.

PMID- 10089511
TI  - Structure of the mutant E92K of [2Fe-2S] ferredoxin I from Spinacia oleracea at
      1.7 A resolution.
AB  - Ferredoxin I (Fd I) from Spinacia oleracea is composed of 97 amino-acid residues
      and a [2Fe-2S] cluster. The crystal structure of the E92K mutant of Fd I was
      solved by molecular replacement and refined to an R factor of 19.6% for 11755
      reflections at 1.7 A resolution. The overall structure and the active centre of
      spinach Fd is highly conserved with respect to ferredoxins of known structure.
      The E92K mutation appears to disturb a hydrogen-bond network which stabilizes the
      loop bearing the [2Fe-2S] cluster. This observation provides a rationale for the
      reduced electron-transfer efficiency displayed by the E92K mutant. Inspection of
      the crystal packing reveals that the side chain of Lys92 is engaged in an
      intermolecular interaction with Asp26 of a symmetry-related molecule. This
      feature may explain why only the mutant E92K and not wild-type Fd I could be
      successfully crystallized.

PMID- 10089512
TI  - Static Laue diffraction studies on acetylcholinesterase.
AB  - Acetylcholinesterase (AChE) is one of nature's fastest enzymes, despite the fact
      that its three-dimensional structure reveals its active site to be deeply
      sequestered within the molecule. This raises questions with respect to traffic of
      substrate to, and products from, the active site, which may be investigated by
      time-resolved crystallography. In order to address one aspect of the feasibility
      of performing time-resolved studies on AChE, a data set has been collected using
      the Laue technique on a trigonal crystal of Torpedo californica AChE soaked with
      the reversible inhibitor edrophonium, using a total X-ray exposure time of 24 ms.
      Electron-density maps obtained from the Laue data, which are of surprisingly good
      quality compared with similar maps from monochromatic data, show essentially the
      same features. They clearly reveal the bound ligand, as well as a structural
      change in the conformation of the active-site Ser200 induced upon binding.

PMID- 10089513
TI  - First experimental evidence for human dentine crystal formation involving
      conversion of octacalcium phosphate to hydroxyapatite.
AB  - Biological apatite-crystal formation is a complex process starting with
      heterogeneous nucleation of inorganic calcium phosphate on an organic
      extracellular matrix [Cuisinier et al. (1995), J. Cryst. Growth, 156, 443-453].
      Further stages of crystal growth are also controlled by the organic matrix and
      both nucleation and growth processes are under cellular control [Mann (1993),
      Nature (London), 367, 499-505]. The final mineral in calcified tissue is
      constituted by poorly crystalline hydroxyapatite (HA) with a low Ca:P ratio,
      containing foreign ions such as carbonate and fluoride. This study reports the
      first observation of octacalcium phosphate (OCP) [Brown (1962), Nature (London),
      196, 1048-1055] in a biological tissue; OCP was found in the central part and HA
      at the extremities of the same crystal of calcifying dentine. This observation is
      of key importance in understanding the first nucleation steps of biological
      mineralization. The presence of OCP in a forming human dentine crystal and the
      observation in the same tissue of nanometer-sized particles with a HA structure
      [Houlle et al. (1997), J. Dent. Res. 76, 895-904] clearly proves that two
      mechanisms, direct nucleation of non-stoichiometric HA crystals and nucleation of
      OCP, occur simultaneously in same area of mineralization. OCP is found to be a
      transient phase during the growth of biological crystals. In small crystals, OCP
      is completely transformed into HA by a hydrolysis reaction (Brown, 1962) and can
      only be detected in larger crystals because of its slow kinetics of
      transformation.

PMID- 10089514
TI  - Crystals of Thermus thermophilus tRNAAsp complexed with its cognate aspartyl-tRNA
      synthetase have a solvent content of 75%. Comparison with other aminoacylation
      systems.
AB  - Thermus thermophilus tRNAAsp, purified from a non-recombinant source, has been
      crystallized in a complex with its cognate dimeric (alpha2) aspartyl-tRNA
      synthetase. Crystals diffract to 2.9 A resolution and belong to space group P63
      with cell parameters a = b = 258, c = 90.9 A. The crystals contain one aspartyl
      tRNA synthetase dimer and two tRNA molecules in the asymmetric unit,
      corresponding to a Vm of 4.85 A3 Da-1 and 75% solvent content. When compared with
      those obtained for globular proteins these values are high, but fall within the
      range observed for other aminoacyl-tRNA synthetases, either free or complexed
      with their tRNAs. A comparative survey is presented here.

PMID- 10089515
TI  - Estimating lysozyme crystallization growth rates and solubility from isothermal
      microcalorimetry.
AB  - A microcalorimetric technique has been developed to measure crystal-growth
      kinetics and enthalpies of crystallization. The enthalpy of crystallization of
      hen egg-white lysozyme in 0.1 M acetate buffer at pH 4.6 was determined at 287 K
      using this technique. The enthalpies were directly measured to be -14.3 +/- 2.0
      and -14.6 +/- 1.3 kcal mol-1 (1 kcal mol-1 = 4.184 kJ mol-1) for 3 and 5% NaCl
      solutions, respectively, which is in good agreement with values estimated from
      previous solubility measurements. Non-linear regression of the transient heat
      flow allowed measurement of the crystal growth rate as a function of protein
      supersaturation as well as the solubility. The crystal growth rates determined by
      this method were found to agree with those in the literature under the same
      solution conditions.

PMID- 10089516
TI  - Crystallization and preliminary X-ray crystallographic analysis of archaeal O6
      methylguanine-DNA methyltransferase.
AB  - Crystals of archaeal O6-methylguanine-DNA methyltransferase (MGMT) from
      hyperthermophilic archaeon Pyrococcus kodakaraensis strain KOD1 have been grown
      at room temperature using polyethylene glycol as a precipitant. The diffraction
      pattern of the crystal extends to 2.0 A resolution at room temperature upon
      exposure to Cu Kalpha radiation. The crystal belongs to the space group P212121
      with unit-cell dimensions of a = 52.8, b = 86.6 and c = 39.9 A. The presence of
      one molecule per asymmetric unit gives a crystal volume per protein mass (Vm) of
      2.3 A3 Da-1 and a solvent content of 48% by volume. A full set of X-ray
      diffraction data was collected to 2.0 A Bragg spacings from the native crystal.

PMID- 10089517
TI  - Purification and preliminary X-ray crystallographic studies of recombinant 7,8
      diaminopelargonic acid synthase from Escherichia coli.
AB  - Recombinant 7,8-diaminopelargonic acid synthase from Escherichia coli, a
      pyridoxal-phosphate-dependent aminotransferase, has been crystallized in space
      groups P21 and C2. Both crystal forms were obtained at pH 7.3 with 21%
      polyethylene glycol and 10% 2-propanol as precipitants. The cell dimensions were
      a = 130, b = 57.5, c = 117 A, beta = 110 degrees for the C2 crystals, and a =
      58.4, b = 55.6, c = 121 A, beta = 96.9 degrees for the P21 crystals, which
      diffract to at least 2.6 and 2.0 A resolution, respectively.

PMID- 10089518
TI  - Crystallization of OmpC osmoporin from Escherichia coli.
AB  - OmpC porin, one of the major outer-membrane proteins of Gram-negative bacteria,
      participates in bacterial osmoregulation by counteracting OmpF porin. Although
      these two osmoporins from Escherichia coli share high sequence homology, their
      crystallization behavior was found to be very different. OmpC could be
      crystallized under a variety of conditions by either microdialysis or hanging
      drop methods using PEG 4000 as precipitant. The crystals belong to space group
      P21 with unit-cell constants a = 117.6, b = 110, c = 298.4 A, beta = 97 degrees.
      They diffract beyond 4 A with a rotating anode and show intense non-Bragg
      scattering.

PMID- 10089519
TI  - Crystallization and preliminary X-ray analysis of the unliganded recombinant
      catalytic subunit of cAMP-dependent protein kinase.
AB  - X-ray diffraction-quality crystals of the unliganded mouse recombinant catalytic
      subunit of cAMP-dependent protein kinase were grown by the hanging-drop vapour
      diffusion technique using 2-methyl-2,4-pentanediol as precipitant. The crystals
      belong to the monoclinic space group P21 with unit-cell parameters a = 48.9, b =
      147.4, c = 54.2 A, beta = 110.2 degrees. A data set to 3.0 A resolution with 92%
      completeness has been collected using synchrotron radiation. The unit cell
      contains four molecules of molecular weight 40 kDa with a corresponding volume
      solvent content of 45%.

PMID- 10089520
TI  - Crystallization and preliminary crystallographic study of tropinone reductase II
      from Datura stramonium.
AB  - Tropinone reductase II is an NADPH-dependent oxidoreductase involved in a plant
      alkaloid metabolism. The enzyme from Datura stramonium has been crystallized
      using 2-methyl-2,4-pentanediol as a precipitant and a macro-seeding technique.
      The crystal belongs to space group P42212, with cell dimensions a = b = 62.8 and
      c = 128.4 A. A data set to 2.6 A resolution has been collected at a cryogenic
      temperature.

PMID- 10089521
TI  - Crystallization of ovine placental lactogen in a 1:2 complex with the
      extracellular domain of the rat prolactin receptor.
AB  - Growth hormone and prolactin control somato-lactogenic biology. While high
      resolution crystal structures have been determined for receptor complexes of
      human growth hormone, no such information exists for prolactin. A stable 1:2
      complex was formed between ovine placental lactogen, a close prolactin homologue,
      and two copies of the extracellular portion of the rat prolactin receptor. Using
      synchrotron radiation, native data have been collected to 2.3 A. Crystals contain
      one complex per asymmetric unit. The crystal structure of this complex will shed
      light on the structural reasons for cross-reactivity and specificity among the
      endocrine hormones, placental lactogen, prolactin and growth hormone.

PMID- 10089522
TI  - Crystallization and preliminary X-ray analysis of a chitinase from the fungal
      pathogen Coccidioides immitis.
AB  - Chitinase is necessary for fungal growth and cell division and, therefore, is an
      ideal target for the design of inhibitors which may act as antifungal agents. A
      chitinase from the fungal pathogen Coccidioides immitis has been expressed as a
      fusion protein with gluathione-S-transferase (GST), which aids in purification.
      After cleavage from GST, chitinase was crystallized from 30% PEG 4000 in 0. 1 M
      sodium acetate pH 4.6. The crystals have a tetragonal crystal lattice and belong
      to space group P41212 or P43212 and diffract to 2. 2 A resolution. The unit-cell
      parameters are a = b = 91.2, c = 95.4 A; there is only one chitinase molecule in
      the asymmetric unit.

PMID- 10089523
TI  - Crystallization and preliminary X-ray analysis of porcine muscle prolyl
      oligopeptidase.
AB  - Prolyl oligopeptidase from pig muscle has been crystallized in complex with an
      inhibitor, using PEG 8000 and calcium acetate as precipitants. The crystals are
      orthorombic and the space group is P212121 with cell dimensions a = 111.8, b =
      101.8, c = 72.4 A. The asymmetric unit contains a single chain of prolyl
      oligopeptidase, corresponding to a specific volume of 2.55 A3 Da-1 and a solvent
      content of 52%. The observed diffraction pattern extends to 2.3 A resolution and
      the native crystals are well suited for structural analysis by X-ray diffraction
      methods.

PMID- 10089524
TI  - Crystallization and preliminary X-ray studies of the Rhizobium meliloti DctD two
      component receiver domain.
AB  - The Rhizobium meliloti DctD two-component receiver domain was expressed in
      Escherichia coli and purified to homogeneity. Crystals were obtained using the
      hanging-drop vapor-diffusion geometry with ammonium phosphate as the precipitant.
      The crystals diffract to 2.3 A and exhibit the symmetry of space group I222 or
      I212121. The unit-cell dimensions are a = 59.0, b = 58.6 and c = 169.8 A. The
      asymmetric unit contains a dimer and the crystals have a Vm of 2.16 A3 Da-1.

PMID- 10089525
TI  - Preliminary crystallographic studies of triosephosphate isomerase (TIM) from the
      hyperthermophilic Archaeon Pyrococcus woesei.
AB  - Recombinant triosephosphate isomerase (TIM) from a hyperthermophilic Archaeon,
      Pyrococcus woesei, has been crystallized. Three crystal forms have been obtained:
      monoclinic, orthorhombic and hexagonal. The monoclinic crystals belong to space
      group P21 with cell dimensions a = 79.1, b = 89.2, c = 145.4 A and beta = 92.8
      degrees, and diffract to at least 2.6 A. The orthorhombic crystals belong to
      space group P21212 with a = 89.4, b = 155.9, c = 79.5 A, and diffract to 2.9 A.
      Diffraction from the hexagonal form showed extensive disorder. The monoclinic
      form contains two tetramers in the asymmetric unit, which are in the same
      orientation but related by a pseudo-centering. The orthorhombic form contains one
      tetramer in the asymmetric unit which is in approximately the same orientation as
      in the monoclinic form. Knowledge of the structure of this hyperthermostable TIM,
      which is tetrameric in contrast to dimeric forms previously observed, will add to
      our understanding of protein thermostability.

PMID- 10089526
TI  - Crystallization and preliminary X-ray diffraction studies of 6-phosphogluconate
      dehydrogenase from Lactococcus lactis.
AB  - 6-Phosphogluconate dehydrogenase is one of the seven enzymes involved in the
      pentose phosphate pathway. Crystals of a mammalian and a protozoan enzyme have
      been obtained previously and structures determined. It is reported here that a
      bacterial 6-phosphogluconate dehydrogenase, from Lactococcus lactis, has been
      purified and used in crystallization trials. Large prisms suitable for a detailed
      structural analysis have been obtained and characterized as orthorhombic, space
      group F222, with a = 70.4, b = 105.7, c = 474.6 A. Diffraction has been observed
      to 2.2 A resolution using synchrotron radiation. Structural analysis, in
      combination with ongoing biochemical characterization, will assist the
      elucidation of the structure-activity relationships of this enzyme.

PMID- 10089527
TI  - Crystallization and preliminary X-ray diffraction studies of alpha-toxin from two
      different strains (NCTC8237 and CER89L43) of Clostridium perfringens.
AB  - The alpha-toxin of Clostridium perfringens is the major virulence determinant for
      gas gangrene in man. The gene encoding the alpha-toxin has been cloned into E.
      coli from two strains of the bacterium (NCTC8237 and CER89L43) and subsequently
      purified to homogeneity. The two strains of alpha-toxin differ by five amino
      acids, resulting in the toxin from NCTC8237 being sensitive to chymotrypsin
      digestion while that from CER89L43 is resistant. The alpha-toxin from each of
      these strains has been crystallized in two different forms by the hanging-drop
      vapour-diffusion method at 293 K. CER89L43 form I crystals belong to space group
      R32 and have two molecules in the crystallographic asymmetric unit and a unit
      cell with a = b = 151.4, c = 195.5 A, alpha = beta = 90, gamma = 120 degrees. The
      crystals diffracted to dmin = 1.90 A. The characteristics of the NCTC8237 form I
      crystals have already been reported. The form II crystals from both strains
      belong to space group C2221 with one molecule in the crystallographic asymmetric
      unit and, for strain CER89L43, have cell dimensions a = 61.05, b = 177.50, c =
      79.05 A, alpha = beta = gamma = 90 degrees, while for strain NCTC8237 the cell
      dimensions are a = 60.50, b = 175.70, c = 80.20 A, alpha = beta = gamma = 90
      degrees. The crystals diffracted to maximum resolutions of 1.85 and 2.1 A for the
      CER89L43 and the NCTC8237 strains, respectively.

PMID- 10089528
TI  - Crystallization and preliminary X-ray analysis of polyamine oxidase from Zea mays
      L.
AB  - Polyamine oxidase catalyses the oxidation of the secondary amino group of
      spermine, spermidine and their acetyl derivatives. The enzyme plays an important
      role in the regulation of polyamine intracellular concentration and is a member
      of the family of flavin-containing amine oxidases. Crystals of maize polyamine
      oxidase have been grown by the hanging-drop vapour-diffusion technique. The
      crystals are in hexagonal space group P6122 (or P6522) with cell dimensions a = b
      = 184.6, c = 280.9 A. A native data set has been collected to 2.7 A resolution at
      a synchrotron radiation source.

PMID- 10089529
TI  - Crystallization and preliminary X-ray diffraction study of lactonohydrolase from
      Fusarium oxysporum.
AB  - The lactonohydrolase from the fungus Fusarium oxysporum AKU 3702 was crystallized
      by the vapour-diffusion procedure in the presence of polyethylene glycol 4000 as
      a precipitant. The crystals belong to the monoclinic space group P21 with unit
      cell parameters a = 156, b = 100, c = 94.1 A, beta = 91.7 degrees. Assuming that
      there are two lactonohydrolase-dimer molecules in the asymmetric unit, the
      crystal volume per unit molecular mass, Vm, is calculated to be 2.94 A3 Da-1.

PMID- 10089530
TI  - Crystallization and preliminary crystallographic analysis of the archaeal intron
      encoded endonuclease I-DmoI.
AB  - Two forms of the archaeal intron-encoded site-specific endonuclease I-DmoI,
      namely I-DmoIc and I-DmoIl, have been purified and crystallized. Crystals of I
      DmoIc are rod-shaped and diffract to 3.0 A resolution, but further analysis was
      hampered by twinning. Crystals of I-DmoIl, which is a six-amino-acid C-terminal
      truncation of I-DmoIc, are plate shaped and belong to space group C2 with cell
      parameters a = 93.72, b = 37.03, c = 55.56 A, beta = 113.4 degrees, with one
      molecule per asymmetric unit (Vm = 2.01 A3 Da-1). The crystals diffract to at
      least 2.3 A resolution. A complete native data set has been measured and
      structure determination is on-going.

PMID- 10089531
TI  - Crystallization and preliminary X-ray diffraction studies of piratoxin II, a
      phospholipase A2 isolated from the venom of Bothrops pirajai.
AB  - The phospholipases A2 (PLA2, E.C. 3.1.1.4, phosphatide sn2 acylhydrolases) are
      the major components of the venom of several snakes. They are responsible for
      several important pharmacological effects observed in ophidian incidents. PLA2
      piratoxin II from Bothrops pirajai has been crystallized by the vapour-diffusion
      technique. X-ray diffraction data have been collected to 2.04 A resolution (90.2%
      complete, Rmerge = 0.070). The space group is P21 and the cell parameters are a =
      46.19, b = 60.36, c = 58.74 A and beta = 96.05 degrees. The structure has been
      solved by molecular replacement using the crystallographic structure of PLA2 from
      Bothrops asper (PDB code 1CLP) as a search model.

PMID- 10089532
TI  - Crystallization and preliminary diffraction data of neurotoxin Ts-gamma from the
      venom of the scorpion Tityus serrulatus.
AB  - Scorpion neurotoxin Ts-gamma was isolated from Tityus serrulatus venom and
      purified to apparent homogeneity by ion-exchange HPLC. Crystals of the toxin were
      grown using polyethylene glycol 6000 as precipitant and were found to belong to
      the monoclinic space group P21 with cell parameters a = 22.20, b = 36.90, c =
      31.57 A, beta = 100.85 degrees. The crystals diffract beyond 1.73 A resolution at
      a synchrotron beamline, being notably stable during X-ray exposure. The structure
      has been solved by molecular replacement using the very high resolution structure
      of Sahara scorpion Androctonus australis Hector (PDB code 1AHO) as a search
      model.

PMID- 10089533
TI  - Crystallization and preliminary X-ray studies of a recombinant calcium-binding
      protein from Entamoeba histolytica.
AB  - A calcium-binding protein (CaBP) of Entamoeba histolytica was purified from an E.
      coli recombinant clone carrying the CaBP gene in a pET-3c expression vector using
      anion-exchange and size-exclusion chromatography. Examination of the amino-acid
      sequence of the recombinant protein suggested that it has four independent EF
      hand motifs. The protein dissolved in cacodylate buffer was crystallized using
      the hanging-drop method with 2-methylpentane-2,4-diol (MPD) as the precipitant. X
      ray diffraction data have been collected on these crystals using a MAR Research
      imaging-plate detector system attached to a Rigaku RU200 rotating-anode X-ray
      generator. The crystals belong to the hexagonal space group P6122 with unit-cell
      dimensions of a = b = 96.21, c = 65.48 A. Preliminary molecular-replacement
      computations suggest that the structure of this protein is likely to be similar
      to that of calmodulin (CAM).

PMID- 10089534
TI  - Crystallization of two related lectins from the legume plant Dolichos biflorus.
AB  - The seed lectin DBL and the related stem and leaves lectin DB58 of the tropical
      legume Dolichos biflorus were crystallized, as well as complexes of DBL with
      adenine and with GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal. The different crystal forms
      of DBL diffract to about 2.8 A, while DB58 crystals diffract to 3.3 A.

PMID- 10089535
TI  - Crystallization and preliminary X-ray crystallographic studies on apolipoprotein
      H (beta2-glycoprotein-I) from human plasma.
AB  - Apolipoprotein-H (Apo-H, Mw approximately 50 kDa) is a carbohydrate-rich human
      plasma protein which exists in blood serum in the free form as well as
      distributed between several classes of lipoproteins. Single crystals of apo-H
      have been obtained and crystallographic data sets have been collected. The
      crystals belong to the orthorhombic space group C2221, with cell dimensions a =
      158. 47, b = 169.25, c = 113.28 A (at 100 K). The data indicate that the
      crystallographic asymmetric unit contains one tetramer of the protein.

PMID- 10089536
TI  - Bacillus subtilis regulatory protein GerE.
AB  - GerE is the latest-acting of a series of factors which regulate gene expression
      in the mother cell during sporulation in Bacillus. The gene encoding GerE has
      been cloned from B. subtilis and overexpressed in Escherichia coli. Purified GerE
      has been crystallized by the hanging-drop vapour-diffusion method using
      polyethylene glycol as a precipitant. The small plate-like crystals belong to the
      monoclinic space group C2 and diffract beyond 2.2 A resolution with a synchrotron
      radiation X-ray source.

PMID- 10089537
TI  - Production, crystallization and diffraction to atomic resolution of an antibody
      Fv specific for the blood-group A oligosaccharide antigen.
AB  - The histoblood-group ABO carbohydrate antigens are well known as important
      factors in blood transfusions, but they can also act as receptors for infectious
      agents and have been implicated in susceptibility to certain carcinomas. A single
      chain variable-domain antigen-binding fragment (scFv) gene based on the known
      sequence of an anti-blood-group-A monoclonal antibody (AC1001) has been
      synthesized and expressed in Escherichia coli. The purified scFv preparation
      existed primarily in the monomeric form but also contained large amounts of
      dimeric and higher oligomeric forms. The corresponding variable-domain antigen
      binding fragment (Fv) was generated by cleaving the VL-VH linker with subtilisin,
      and its activity was demonstrated by surface plasmon resonance with an
      immobilized bovine serum albumin-A-trisaccharide conjugate (KD = 290 microM).
      AC1001 Fv crystals grown in the presence of N-acetylgalactosamine diffracted to
      0.93 A resolution. This is the first reported example of a crystal of an antibody
      antigen-binding fragment diffracting to atomic resolution.

PMID- 10089538
TI  - Overexpression, purification, crystallization and preliminary X-ray diffraction
      analysis of the receiver domain of PhoB.
AB  - PhoB is the response regulator of the E. coli two-component signal transduction
      system for phosphate regulation. It is a transcription factor that activates more
      than 30 genes of the pho regulon. Crystals of the receiver domain of PhoB were
      obtained by applying the hanging-drop vapour-diffusion method. X-ray diffraction
      data have been collected using synchrotron radiation to 1.88 A resolution. The
      crystals belong to the orthorhombic space group P212121 with unit-cell constants
      a = 34.11, b = 60.42, c = 119.97 A. The Matthews parameter suggests that PhoB
      crystallizes with two molecules per asymmetric unit, suggesting that activating
      dimerization occurs in the crystal.

PMID- 10089539
TI  - Expression, purification and preliminary X-ray crystallographic analysis of PsaA,
      a putative metal-transporter protein of Streptococcus pneumoniae.
AB  - The putative metal-transporter protein PsaA of Streptococcus pneumoniae is of
      potential interest both as a vaccine and also as a drug target. The
      overexpression of the protein in E. coli, and its subsequent purification and
      crystallization are described. The crystals are rectangular rods and diffract to
      beyond 2.7 A resolution. The crystal space group is P212121 with unit-cell
      dimensions a = 59.9, b = 66.5 and c = 69.9 A.

PMID- 10089540
TI  - Crystallization and preliminary crystallographic analysis of glyceraldehyde 3
      phosphate dehydrogenase from Sacchromyces cerevisiae (baker's yeast).
AB  - Two related and not thoroughly resolved issues in biochemistry concern the role,
      if any, of enzyme surfaces in routine metabolism and the method by which
      metabolic intermediates move between enzyme active sites during multi-step
      degradation or synthesis. An important enzyme for which a detailed three
      dimensional structural analysis has been initiated is yeast glyceraldehyde 3
      phosphate dehydrogenase (yGAP-DH). This enzyme is active as a tetramer of total
      molecular weight of 145 kDa and requires nicotinamide adenine dinucleotide (NAD+)
      as cofactor. In this report, the crystallization and preliminary crystallographic
      characterization of several crystal forms of yGAP-DH are described. Of the five
      distinct crystal forms, the most suitable was found to contain the holo-enzyme,
      and the crystals were grown by the vapor-diffusion method using polyethylene
      glycol 6000 as precipitant, sodium acetate as buffer (pH 4.6), and NAD+ and
      dithiothreitol as additives. The crystals belong to the orthorhombic space group
      P21212, with cell dimensions of a = 87.33, b = 96.11 and c = 115.34 A. These
      crystals are mechanically strong, relatively stable in the X-ray beam and
      diffract X-rays (from a normal rotating-anode radiation source) to better than 2
      A resolution. A full 2.1 A resolution diffraction data set (98% completion) has
      been measured. The three-dimensional structures of related GAP-DH enzymes from
      several other sources have been determined and reported, and are available for a
      molecular replacement structure solution.

PMID- 10089542
TI  - Bioethics and public health.

PMID- 10089541
TI  - Expression, crystallization and preliminary X-ray analysis of the E2
      transactivation domain from papillomavirus type 16.
AB  - The N-terminal transactivation domain of the E2 protein from human papillomavirus
      type 16 has been crystallized by vapour diffusion. Crystals belong to the space
      group P3121 (or P3221) with unit-cell dimensions a = b = 54.3, c = 155.5 A. There
      is one molecule per asymmetric unit with a solvent content of 55%. Crystals
      diffract to at least 2.5 A resolution and complete X-ray data to 3.4 A have been
      collected on a conventional laboratory source. This 201 amino-acid domain of the
      E2 protein has been shown to interact functionally with both the HPV E1 protein
      and at least three cellular transcription factors, to fulfil its role in the
      control of viral transcription and replication. A knowledge of the structural
      basis of these multiple interactions should lead to a fuller understanding of the
      mechanism of action of this key regulator of the HPV life cycle.

PMID- 10089543
TI  - The principles of medical ethics and medical research.
AB  - In this paper I discuss the application of the principles of medical ethics and
      of medical research to the case of children and others whose consent to treatment
      and to research is problematic. Public health depends substantially on the
      possibility of ongoing research into all conditions which affect the health of
      the people. Constraints on this research are therefore a public health issue.
      Moreover and more importantly the possibility of predictive testing and indeed of
      screening for health-relevant conditions is an important public health tool, and
      limitations on the use of this tool are of great significance to public health
      medicine. Having considered the particular problems created by research and
      predictive testing on children for late-onset conditions I go on to discuss
      research on those whose consent is problematic more generally. I conclude with
      radical recommendations for the reform of The Declaration of Helsinki and of the
      International Ethics Guidelines for Biomedical Research Involving Human Subjects,
      prepared by the Council for International Organizations of Medical Sciences
      (CIOMS).

PMID- 10089544
TI  - Paradigm shift, metamorphosis of medical ethics, and the rise of bioethics.
AB  - Both the increasing incorporation of medical technology and new social demands
      (including those for health care) beginning in the 1960s have brought about
      significant changes in medical practice. This situation has in turn sparked a
      growth in the philosophical debate over problems pertaining to ethical practice.
      These issues no longer find answers in the Hippocratic ethical model. The authors
      believe that the crisis in Hippocratic ethics could be described as a period of
      paradigm shift in which a new set of values appears to be emerging. Beginning
      with the bioethics movement, the authors expound on the different ethical
      theories applied to medical practice and conclude that principlism is the most
      appropriate approach for solving the new moral dilemma imposed on clinical
      practice.

PMID- 10089545
TI  - On the concept of eugenics: preliminaries to a critical appraisal.
AB  - This paper's main issue is linked to what can be foreseen as the increasing
      capability of medical genetics to modify the genetic composition of the human
      species through direct interventions in the human genome for medical and non
      medical purposes, i.e., the "risk" of a resurgence of eugenics. In current
      discussions on the topic (briefly presented in the first section), the "phantom
      of eugenics" is raised several times, but there is a great deal of confusion on
      what counts as eugenics, partly because of broad conceptual disagreement over the
      notion itself. Furthermore, according to some scholars there is no hope of
      overcoming this unsatisfactory conceptual uncertainty. Partly challenging this
      opinion, the second and third sections of this paper attempt to identify some
      basic features which could be seen as intrinsically linked to the notion of
      eugenics, with the aim of reducing the range of conceptual disagreement as a
      preliminary step in bringing into focus what exactly is wrong with practicing
      eugenics. The subsequent sections deal with the substantive issue of whether or
      not to practice eugenics from the point of view of the interest of future
      generations in the human species' genetic composition. The main moral arguments
      for and against eugenics are examined from the point of view of our obligations
      towards future generations, and the conclusion is in favor of a cautious "open
      door" position.

PMID- 10089546
TI  - Bioethical language and its dialects and idiolects.
AB  - In their search for answers to the relevant theoretical questions on importing
      knowledge in practical ethics, the authors take an instrumental approach to
      metaphor. This figure of language allows one to compare language and linguistic
      variants to bioethics and knowledge. As defined by the dictionary, an 'idiom' is
      the official language of a nation, a 'dialect' is a regional variant of an idiom,
      and an 'idiolect' is an individual variant of a dialect. The bioethical idiom is
      thus seen as a linguistic set constituting a 'bioethical nation'. Since it is
      situated above particular dialects, it exercises more than a regulatory role over
      the discipline. In this article, in order to focus on the process of transmission
      of knowledge in bioethics, the authors chose Diego Gracia's work as a
      paradigmatic reference to the question on the transculturation of dialects and
      the relations in bioethics which are considered 'peripheral' or 'central'.
      Although this researcher found the key question pointing to the core of the
      problem of importing dialects, he is still searching for a proper answer to the
      cultural/bioethical context/contradiction.

PMID- 10089547
TI  - Sanitary justice in scarcity.
AB  - Justice in health care and the allocation of scarce medical resources must be
      analyzed differently in affluent as compared to economically weaker societies.
      The protective functions of the state must be extended to cover basic needs for
      those too poor to meet them on their own. Medical needs are a high priority,
      since poor health hampers the ability to secure other basic needs. The state may
      operate as either a health care provider or supervisor, guaranteeing that
      citizens be treated fairly by nongovernmental institutions. Two-tiered systems
      with a vigorous private heath care sector are compatible with the explicit right
      to health care, provided the private tier operates without directly or indirectly
      draining public funds.

PMID- 10089548
TI  - The Dolly case, the Polly drug, and the morality of human cloning.
AB  - The year 1996 witnessed the cloning of the lamb Dolly, based on the revolutionary
      somatic cell nuclear transfer (SCNT) technique, developed by researchers from the
      Roslin Institute in Edinburgh, Scotland. This fact marked a relevant
      biotechnoscientific innovation, with probable significant consequences in the
      field of public health, since in principle it allows for expanding possibilities
      for the reproductive autonomy of infertile couples and carriers of diseases of
      mitochondrial origin. This article expounds on 1) the experiment's technical data
      and the theoretical implications for the biological sciences; 2) the public's
      perception thereof and the main international documents aimed at the legal and
      moral regulation of the technique; and 3) the moral arguments for and against
      cloning, from the point of view of consequentialist moral theory. We conclude
      that in the current stage of the debate on the morality of cloning, in which
      there are no cogent deontological arguments either for or against, weighing the
      probability of risks and benefits is the only reasonable way of dealing with the
      issue in societies that consider themselves democratic, pluralistic, and
      tolerant.

PMID- 10089549
TI  - The morality of assisted reproduction and genetic manipulation.
AB  - The author analyzes the pros and cons of various forms of assisted reproduction,
      including the use of so-called 'genetic manipulation'. He shows how in ethics the
      only arguments with any chance of reaching a consensus (or at least an agreement)
      are those of the rational type, based on universally acceptable ethical
      principles or corroborated by empirical facts and real life experience (as the
      starting point for identifying problems requiring analysis). After an analysis in
      which he identifies the incoherence and inconsistency of arguments against
      assisted reproduction, the author defends the right of human beings to decide
      autonomously about the most healthy forms of procreation, including those
      involving genetic manipulation. His starting point is the moral principle by
      which it is morally preferable to intervene in natural processes (as opposed to
      not intervening) whenever this implies preventing and reducing disease and
      suffering.

PMID- 10089550
TI  - Apocalypse...now? Molecular epidemiology, predictive genetic tests, and social
      communication of genetic contents.
AB  - The author analyzes the underlying theoretical aspects in the construction of the
      molecular watershed of epidemiology and the concept of genetic risk, focusing on
      issues raised by contemporary reality: new technologies, globalization,
      proliferation of communications strategies, and the dilution of identity
      matrices. He discusses problems pertaining to the establishment of such new
      interdisciplinary fields as molecular epidemiology and molecular genetics.
      Finally, he analyzes the repercussions of the social communication of genetic
      content, especially as related to predictive genetic tests and cloning of
      animals, based on triumphal, deterministic metaphors sustaining beliefs relating
      to the existence and supremacy of concepts such as 'purity', 'essence', and
      'unification' of rational, integrated 'I's/egos'.

PMID- 10089551
TI  - Reflections on bioethics: consolidation of the principle of autonomy and legal
      aspects.
AB  - The author highlights the importance of emotions in all ethical reflections. He
      describes the most common positions of ethicists employing duties and rights as
      the basis for ethical thought. The author, goes to Freudian theory as viewed by
      the utilitarians, stating that the 'quest for pleasure' is not necessarily
      egocentric, especially for adults. For example, the feeling of solidarity emerges
      'from the inside out', making irrelevant all the emphasis laid on obedience to
      duty (from the outside in). The article questions the essence of Kantian theory,
      based exclusively on 'reason' with disregard for feelings, by establishing what
      he considers a 'positivist' view of rational thought. It emphasizes the principle
      of autonomy, which it seen as basically opposing the principles of beneficence
      and fairness. It is proposed that the latter should be seen as what he calls
      heteronomy (a concept different from that of the rational ethicists). In theory,
      autonomy is not assigned to anyone on the basis of an external assessment. Any
      intervention in individual autonomy must be made (by the intervenor) when it
      becomes imperative in the defense of social or cultural values. The article
      distinguishes between ethics and morals) and states that the sole acceptable
      ethical principle is that ethics (theoretically) has no principle.

PMID- 10089552
TI  - Ethics and animal experimentation: what is debated?
AB  - The purpose of this article is to raise some points for an understanding of the
      contemporary debate over the ethics of using animals in scientific experiments.
      We present the various positions from scientific and moral perspectives
      establishing different ways of viewing animals, as well as several concepts like
      'animal ethics', 'animal rights', and 'animal welfare'. The paper thus aims to
      analyze the importance and growth of this debate, while proposing to expand the
      academic approach to this theme in the field of health.

PMID- 10089553
TI  - Population, ethics, and equity.
AB  - Demography is impregnated, more or less explicitly, with ethical contents. This
      is apparent in the words used to support data, which change over time (e.g., the
      term "illegitimate child" is no longer used). Ethical principles must be analyzed
      because demography concerns both public policies and individual choice. There is
      a conflict in this area between the idea of the ethical state, dictating personal
      behaviors to citizens, and that of decisions based on freedom, supported by three
      shared values: human rights, pluralism, and equity. This paper examines how these
      could be reinterpreted in the context of choices regarding population.

PMID- 10089554
TI  - Exercise at menopause: a critical difference.
AB  - Even at menopause, fitness can reduce the risk of heart disease, osteoporosis,
      and diabetes, yet only 38% of women over age 19 exercise regularly. A sports
      medicine expert recommends that exercise be encouraged and prescribed, even for
      women with a variety of comorbidities.

PMID- 10089556
TI  - OB/GYN virtual consult--menorrhagia for 6 months in a 31-year-old.
AB  - What treatment options would you advise for a young woman with vaginal bleeding
      of 6 months' duration? Malcolm Griffiths, MD, in the Department of Obstetrics and
      Gynaecology, Luton & Dunstable Hospital, Luton, UK, moderates this case.

PMID- 10089557
TI  - Hormone alterations in breast cancer: examining the hypotheses.
AB  - Many of the epidemiologic risk factors for breast cancer offer clinicians little
      help in anticipating who is likely to be struck with the disease or how to
      prevent it. There are only a handful of clinically significant risk factors for
      breast cancer. These include being a woman, growing older, already having breast
      cancer in 1 breast, and having a first-degree relative (mother, sister, or
      daughter) who has been diagnosed with breast cancer. Most risk factors have a
      weak association with breast cancer, occur too infrequently, or are physiologic
      events not amenable to intervention. In recent years, the search for breast
      cancer causes has led to the identification of genetic markers that seem to
      predispose some women to breast cancer. For decades, however, researchers have
      been assessing and analyzing hormonal changes in the hope of finding a
      predictable breast cancer marker or cause that can easily be manipulated to
      prevent or more effectively treat the disease. Nearly a dozen hormonal hypotheses
      of breast cancer causes have been proposed -- among them estrogen excess, low
      luteal-phase progestational activity, adrenal androgen deficiency, ovarian
      androgen excess, melatonin deficiency, prolactin excess, and thyroid
      insufficiency. For most, the data are equivocal and inconclusive. The androgen
      deficiency hypotheses, however, may have some bearing on premenopausal breast
      cancer, and the ovarian dysfunction hypothesis may have some bearing on
      postmenopausal breast cancer.

PMID- 10089560
TI  - Correction: Renal Atrophy Associated with Long-Term Treatment with Indinavir.

PMID- 10089559
TI  - Virtual consult--pregnant woman with sickle-cell disease.
AB  - A young woman in her 20s with a lifelong history of sickle-cell disease presents
      with sickle-cell crisis while in active labor. After delivery of the neonate via
      cesarean section, her fever spikes to nearly 106 F (41.1 C) and stays there.
      Clinicians are invited to comment on this case in a discussion moderated by
      Joseph Pastorek, MD, FACOG.

PMID- 10089561
TI  - Correction: Inadequate Prescription-Drug Coverage for Medicare Enrollees -- A
      Call to Action.

PMID- 10089562
TI  - Effects of intrapancreatic neuronal activation on cholecystokinin-induced
      exocrine secretion of isolated perfused rat pancreas.
AB  - The role of intrapancreatic neurons in the action of cholecystokinin (CCK) on
      pancreatic exocrine secretion of the totally isolated, perfused rat pancreas was
      investigated. Intrapancreatic neurons were activated by applying electrical field
      stimulation (EFS) to the isolated pancreas for 45 min. When applying EFS,
      spontaneous pancreatic secretions of fluid and amylase increased until the second
      15-min period of EFS and then decreased during the third 15-min period. Atropine
      (2 microM) notably reduced the EFS-evoked pancreatic secretions of fluid and
      amylase. The CCK-induced (10 pM) pancreatic secretions of fluid and amylase
      elevated further in the first 15-min period of EFS and then gradually resumed to
      the levels observed during application of CCK alone in the third 15-min period of
      EFS. However, the CCK-induced pancreatic secretions remained elevated even in the
      third 15-min period of EFS when an action of endogenous somatostatin was
      inhibited by cyclo-(7-aminoheptanonyl-Phe-d-Trp-Lys-Thr[BZL]) (10 nM) or
      pertussis toxin (200 ng/ml). EFS further elevated spontaneous exocrine secretion
      by the cysteamine-treated (300 mg/kg) pancreas, but this was markedly reduced, to
      normal levels, by infusing somatostatin (100 pM). EFS increased the numbers of
      immunoreactive somatostatin cells in the Langerhans' islets. The results indicate
      that intrapancreatic neuronal activation influences CCK-induced pancreatic
      secretions in a dual-phase pattern in the rat: an increase during the early phase
      and a decrease during the late phase. Endogenous somatostatin released from the
      islets appears to inhibit the enhancing effect of neuronal activation on CCK
      induced pancreatic secretion. Of the intrapancreatic neurons, the cholinergic
      ones appear to predominate in EFS's effects on CCK-induced pancreatic secretion.

PMID- 10089563
TI  - Heterogeneity of Na+/K+-ATPase from rectal gland of Squalus acanthias is not due
      to alpha isoform diversity.
AB  - Purified Na+/K+-ATPase (EC 3.6.1.37) isolated from the rectal gland of Squalus
      acanthias was characterized in ouabain-binding studies and with respect to
      isoform(s) of the alpha peptide. To avoid enzyme inactivation [3H]ouabain
      equilibrium binding was carried out at 20 degrees C. The heterogeneity of Na+/K+
      ATPase isolated from shark rectal gland was similar in [3H]ouabain binding as
      previously seen in hydrolytic studies. The binding isotherms were compatible with
      the existence of a high-affinity (Kdis 0.69 nM) and a low-affinity (Kdis 42 nM)
      component of 1.46 and 0.79 nmol.(mg protein)-1, respectively. In Western blots
      the alpha peptide of the enzyme hybridized with an isoform-specific polyclonal
      antibody raised to an alpha3-specific region of the large intracellular domain of
      rat Na+/K+-ATPase, but not with the supposed alpha3-specific monoclonal antibody
      MA3-915 with its epitope near the N-terminus. Semi-quantitative analysis of the
      reaction of the alpha3-specific polyclonal antibody with the alpha peptide from
      the shark enzyme compared to the reaction with alpha peptide from rat brain
      enzyme indicated that this region is not exactly the same in the two species. The
      alpha peptide of shark enzyme was not recognized by alpha1- or alpha2-specific
      polyclonal antibodies, or by the alpha1-specific monoclonal antibodies 3B and F6.
      The large intracellular domain of Na+/K+-ATPase from shark rectal gland thus
      seems to be alpha3-like and no alpha isoform heterogeneity seems able to account
      for the heterogeneity seen in ouabain binding.

PMID- 10089564
TI  - L-type calcium channels unmasked by cell-permeant Ca2+ buffer at mouse motor
      nerve terminals.
AB  - The involvement of the different types of voltage-dependent calcium channels
      (VDCC) in both DM-BAPTA-AM-incubated and EGTA-AM-incubated mature mice levator
      auris neuromuscular junctions (NMJ) was studied. We evaluated the effects of
      omega-agatoxin IVA (omega-Aga IVA), nitrendipine and omega-conotoxin GVIA (omega
      CgTX) (P/Q-, L- and N-type VDCC blockers, respectively) on perineurial calcium
      currents (ICa) and nerve-evoked transmitter release. The application of omega-Aga
      IVA (100 nM) drastically reduced perineurial ICa (>90%) and nerve-evoked
      transmitter release (>90% of reduction in quantal content, m) at both DM-BAPTA-AM
      incubated and EGTA-AM-incubated NMJ. The L-type VDCC antagonist nitrendipine (10
      microM) caused a significant reduction (23+/-9%, n=5) of perineurial ICa at DM
      BAPTA-AM-incubated NMJ. In addition, after the block of P/Q-type VDCC with omega
      Aga IVA (100 nM), nitrendipine reduced (>90%, n=2) the remaining perineurial ICa.
      Such reduction was not observed at EGTA-AM-incubated NMJ, before or after the
      total block of P/Q-type VDCC. Moreover, nitrendipine did not significantly reduce
      the quantal content of DM-BAPTA-AM-incubated NMJ. Finally, the application of
      omega-CgTX (5 microM) did not significantly affect perineurial ICa or nerve
      evoked transmitter release at either DM-BAPTA-AM-incubated or EGTA-AM-incubated
      NMJ. These results show the existence of a nitrendipine-sensitive, L-type
      component of perineurial ICa in DM-BAPTA-AM-incubated NMJ of mature mice.

PMID- 10089565
TI  - Effects of the protein kinase A inhibitor H-89 on Ca2+ regulation in isolated
      ferret ventricular myocytes.
AB  - We investigated the effects of a protein kinase A (PKA) inhibitor, H-89 {N-[2-(p
      bromocinnamylamino)ethyl]-5-iso-quinolinesulphonamide}, on Ca2+ regulation in
      Fura-2-loaded ferret myocytes. H-89 (10 micromol/l) decreased the amplitude of
      the Fura-2 transient to 28. 2+/-4.3% (P<0.001) of control and prolonged its
      duration, characterized by a decrease in the rate of decline of Ca2+ to diastolic
      levels: t1/2 increased from 311+/-35 ms to 547+/-43 ms (P<0.001, n=7). Reduced
      Ca2+ uptake by the sarcoplasmic reticulum (SR) in the presence of H-89 was also
      indicated by a decrease in the SR Ca2+ content, as assessed with caffeine. The
      apparent slowing of the SR Ca2+-ATPase was not caused by changes in
      phosphorylation of phospholamban (PLB). However, Ca2+ uptake in microsomal
      vesicles prepared from canine hearts and fast-twitch rat skeletal muscle (which
      lacks PLB) was decreased by 34.1 and 46.8% (n=3), respectively, suggesting that H
      89 has a direct inhibitory effect on the SR Ca2+-ATPase. In electrophysiological
      experiments, 5.0 micromol/l H-89 decreased the L-type Ca2+ current (ICa) by 39.5%
      (n=6) and slowed the upstroke of the action potential and, in some cases, caused
      loss of excitability without changes in the resting membrane potential. In
      summary, data show that [Ca2+ ]i regulation, and hence contraction, is sustained
      by PKA-mediated phosphorylation, even in the absence of beta-agonists. However,
      the use of H-89 as a tool to study the role of this signalling pathway is limited
      by the non-specific effects of H-89 on the SR Ca2+-ATPase.

PMID- 10089566
TI  - Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up
      regulation in human monocytes by gp41 envelope protein of human immunodeficiency
      virus type 1.
AB  - Our previous results show that recombinant gp41 (aa565-647), the extracellular
      domain of HIV-1 transmembrane glycoprotein, stimulates interleukin-10 (IL-10)
      production in human monocytes. The signal cascade transducing this effect is not
      yet clear. In this study, we examined whether gp41-induced IL-10 up-regulation is
      mediated by the previously described synergistic activation of cAMP and NF-kappaB
      pathways. gp41 induced cAMP accumulation in monocytes in a time- and
      concentration-dependent manner and the adenylate cyclase inhibitor SQ 22536
      suppressed gp41-induced IL-10 production in monocytes. In contrast, gp41 failed
      to stimulate NF-kappaB binding activity in as much as no NF-kappaB bound to the
      main NF-kappaB-binding site 2 of the IL-10 promoter after addition of gp41. We
      also examined the involvement of other signal transduction pathways. Specific
      inhibitors of p70(S6)-kinase (rapamycin), and Gi protein (pertussis toxin),
      prevented induction of IL-10 production by gp41 in monocytes, while inhibitors of
      the phosphatidylinositol 3-kinase (PI 3-kinase) (wortmannin) and mitogen
      activated protein kinase (MAPK) pathway (PD 98059) did not. Thus HIV-1 gp41
      induced IL-10 up-regulation in monocytes may not involve NF-kappaB, MAPK, or PI 3
      kinase activation, but rather may operate through activation of adenylate cyclase
      and pertussis-toxin-sensitive Gi/Go protein to effect p70(S6)-kinase activation.

PMID- 10089567
TI  - The effects of interfering with GTP-binding proteins on the activation mechanism
      of calcium release-activated calcium current.
AB  - In electrically non-excitable cells, Ca2+ entry is mediated predominantly by the
      store-operated Ca2+ influx pathway, which is activated by emptying the
      intracellular Ca2+ stores. Just how the Ca2+ content of the stores is
      communicated to the activity of store-operated Ca2+ channels in the plasma
      membrane is unclear. It has been suggested that, in some cell types, the link is
      accomplished by either a small or a heterotrimeric GTP-binding protein, which is
      inhibited by guanosine 5'-O-(3-thiotriphosphate) (GTP[gamma-S]) and, in some
      cases, pertussis toxin. Using the whole-cell patch-clamp technique to directly
      measure the store-operated Ca2+ current ICRAC (Ca2+-release-activated Ca2+
      current) in RBL cells, we report that manipulations designed to interfere with
      GTP-binding protein activity (dialysis with GTP[gamma-S], exposure to pertussis
      toxin) routinely fail to affect the activation of ICRAC. However, these agents
      alter the activity of a K+ current in the same cells, demonstrating biological
      activity. Furthermore, activation of ICRAC does not seem to require the presence
      of a pre-existing diffusible messenger in the cytoplasm to any appreciable extent
      because the current reaches the same amplitude irrespective of the whole-cell
      dialysis time. We conclude that neither a mobile pre-existing molecule nor a GTP
      dependent step is necessary for the activation of ICRAC in RBL-1 cells.

PMID- 10089568
TI  - Activation of wild-type and deltaF508-CFTR by phosphodiesterase inhibitors
      through cAMP-dependent and -independent mechanisms.
AB  - The cAMP-dependent activation of the cystic fibrosis transmembrane conductance
      regulator (CFTR) and its modulation through inhibition of phosphodiesterases
      (PDE) were studied with the cell-attached patch-clamp technique in Calu-3 cells
      (expressing endogenous CFTR) and NIH3T3 cells [expressing either wild-type (Wt)
      CFTR or DeltaF508-CFTR]. In Calu-3 cells, CFTR current was augmented by
      increasing concentrations of 8-(4-chlorophenylthio)-adenosine 3', 5'-cyclic
      monophosphate (CPT-cAMP) and reached a saturating level at >/=60 microM. Varying
      the forskolin concentration also modulated CFTR activity; 10 microM was maximally
      effective since supplemental application of 200 microM CPT-cAMP had no additional
      effect. Activation of CFTR by increasing the cAMP concentration occurs through an
      increase of the NPo (product of the number of functional channels and the open
      probability) since the single-channel amplitude remains unchanged. In Calu-3 and
      NIH3T3-Wt cells, PDE inhibitors, milrinone (100 microM), 8-cyclopentyl-1, 3
      dipropylxanthine (CPX, 25 microM), and 3-isobutyl-1-methylxanthine (IBMX, 200
      microM), did not enhance CFTR current initially activated with 10 microM
      forskolin, but each potentiated CFTR activity elicited with a submaximal
      forskolin concentration (e.g., 100 nM) and prolonged the deactivation of CFTR
      channel current upon removal of forskolin. Millimolar IBMX increased the NPo of
      both Wt- and DeltaF508-CFTR even under maximal cAMP stimulation. Quantitatively,
      these effects of millimolar IBMX on NPo approximate those of genistein, which
      potentiates the cAMP-dependent CFTR activity via a mechanism that does not
      involve increases in cellular cAMP. Thus, depending on the concentration, PDE
      inhibitors may affect CFTR through different mechanisms.

PMID- 10089569
TI  - Mitochondrial function in human skeletal muscle is not impaired by high intensity
      exercise.
AB  - The hypothesis that high-intensity (HI) intermittent exercise impairs
      mitochondrial function was investigated with different microtechniques in human
      muscle samples. Ten male students performed three bouts of cycling at 130% of
      peak O2 consumption (V.O2,peak). Muscle biopsies were taken from the vastus
      lateralis muscle at rest, at fatigue and after 110 min recovery. Mitochondrial
      function was measured both in isolated mitochondria and in muscle fibre bundles
      made permeable with saponin (skinned fibres). In isolated mitochondria there was
      no change in maximal respiration, rate of adenosine 5'-triphosphate (ATP)
      production (measured with bioluminescence) and respiratory control index after
      exercise or after recovery. The ATP production per consumed oxygen (P/O ratio)
      also remained unchanged at fatigue but decreased by 4% (P<0.05) after recovery.
      In skinned fibres, maximal adenosine 5'-diphosphate (ADP)-stimulated respiration
      increased by 23% from rest to exhaustion (P<0.05) and remained elevated after
      recovery, whereas the respiratory rates in the absence of ADP and at 0.1 mM ADP
      (submaximal respiration) were unchanged. The ratio between respiration at 0.1 and
      1 mM ADP (ADP sensitivity index) decreased at fatigue (P<0.05) but after the
      recovery period was not significantly different from that at rest. It is
      concluded that mitochondrial oxidative potential is maintained or improved during
      exhaustive HI exercise. The finding that the sensitivity of mitochondrial
      respiration to ADP is reversibly decreased after strenuous exercise may indicate
      that the control of mitochondrial respiration is altered.

PMID- 10089570
TI  - Desensitization reduces amplitudes of quantal end-plate currents after a single
      preceding end-plate current in mouse muscle.
AB  - While in membrane patches nicotinic channels from end-plates desensitize with
      time constants of 10-100 ms and recover with time constants of 100-200 ms, doubts
      remain as to whether such rapid reactions are also found in intact neuromuscular
      junctions. Therefore, the desensitization effected by a single end-plate current
      (EPC) on monoquantal EPCs (qEPCs) was studied. Using a published reaction scheme
      for the adult end-plate receptor, the desensitizing effects of an EPC on a
      following one were simulated. Twenty milliseconds after an EPC, a subsequent qEPC
      was reduced to 90% of control, and to 70-80% if acetylcholine esterase (AChE) was
      blocked. EPCs were elicited and recorded through a macropatch electrode. Series
      of four EPCs (control qEPC, conditioning EPC, test qEPC 1 and 2) were repeated
      several thousand times and the amplitudes and decay time constants of the qEPCs
      were evaluated. A highly significant average depression of the qEPC to 96.4% of
      control was found 20 ms after the conditioning EPC; if the AChE was blocked the
      depression after 40 ms was to 76% of control. Under both conditions, the time
      constant of recovery from desensitization was below 100 ms. The time constant of
      decay of the qEPC, taudecay, tended to be slightly shortened during depression in
      the presence of AChE. If AChE was blocked, taudecay was lengthened to 130-140% of
      control after a preceding EPC, and this lengthening outlasted the depression of
      the EPC amplitude by a second. These changes in taudecay are not predicted by the
      channel reaction scheme, and possible additional modulatory effects are
      discussed.

PMID- 10089571
TI  - Direct effects of tolbutamide on mitochondrial function, intracellular Ca2+ and
      exocytosis in pancreatic beta-cells.
AB  - Using the whole-cell voltage-clamp method to measure ATP-sensitive K+(KATP)
      currents, changes in cell capacitance to measure secretion and microfluorimetry
      to monitor intracellular Ca2+ and mitochondrial function, we have investigated
      the direct effect of sulphonylureas on exocytosis in pancreatic beta-cells.
      Tolbutamide (100 microM) and 100 nM 4-beta-12-phorbolmyristate-13-acetate (PMA),
      which activates the protein kinase C (PKC) isoforms found in beta-cells,
      potentiated exocytosis in a non-additive manner. These effects were blocked by
      down-regulation of PKC. Our data support the idea that tolbutamide can potentiate
      secretion from beta-cells via a PKC-dependent pathway. Because PKC and
      sulphonylureas can modulate the activity of KATP channels, we explored whether
      the above effects are caused by inhibition of this channel. PMA increased whole
      cell KATP currents but did not affect their sensitivity to tolbutamide. Down
      regulation of PKC affected neither the magnitude nor the tolbutamide sensitivity
      of the KATP current. Both tolbutamide and the mitochondrial uncoupler FCCP (1
      microM) mobilized intracellular Ca2+ and prolonged Ca2+ transients elicited by
      cholinergic mobilization of intracellular Ca2+ stores. Tolbutamide (0.1-0.5 mM),
      like FCCP, depolarized the mitochondrial membrane potential and activated KATP
      currents. We suggest that sulphonylureas can directly potentiate exocytosis by
      impairing mitochondrial function and Ca2+ handling, which ultimately leads to
      activation of Ca2+-dependent enzymes such as PKC.

PMID- 10089572
TI  - Microelectrode measurements of the effects of basolateral adenosine in polarized
      human intestinal epithelial cells in culture.
AB  - Activation of the basolateral receptor for adenosine in HT-29cl.19A cells, by 100
      microM adenosine, increased the equivalent short-circuit current (DeltaIsc= 24+/
      2 microA/cm2), depolarized the intracellular potential (DeltaVa= 26+/-2 mV) and
      decreased the fractional apical membrane resistance (DeltafRa=-0.48). The changes
      in all parameters reached their peak values simultaneously. This suggests that
      the primary action of the adenosine-activated pathway is on only one membrane.
      Bumetanide inhibited the transepithelial response and repolarized the cell
      potential. After preincubation with 100 microM forskolin, application of 300
      microM adenosine caused a significant further change in Va, Isc, the
      transepithelial potential (Vt) and fRa. Together with the results from ion
      replacement studies, the observations indicate that adenosine activates channels
      other than the cystic fibrosis transmembrane conductance regulator (CFTR). The
      rank order of potencies of adenosine and adenosine analogues implies that the
      receptor is of the A2 subtype. Preincubation with 4-bromophenacyl bromide (4-BPB)
      inhibited the effect of an adenosine analogue by 50%, indicating that activation
      of phospholipase A2 may be involved in the adenosine-induced response.

PMID- 10089573
TI  - Direct inhibitory effect of nicardipine on basolateral K+ channels in human
      colonic crypts.
AB  - The most abundant basolateral K+ channels in human colonic crypt cells have a low
      conductance (23 pS), respond to increases in intracellular Ca2+ and cAMP, and
      have been implicated in intestinal electrogenic Cl- secretion. The effect of
      nicardipine on the activity of these K+ channels was examined by patch-clamp
      recording in the cell-attached and excised inside-out configurations from the
      basolateral membrane of single crypts isolated from biopsied samples of human
      distal colon. During cell-attached recordings, addition of 2 micromol/l
      nicardipine to crypts pretreated with 200 micromol/l dibutyryl cAMP decreased
      single-channel open probability by 87%, but in parallel studies nicardipine had
      no effect on the intracellular Ca2+ concentration. Using inside-out patches from
      crypts pretreated with dibutyryl cAMP (bathed in 1.2 mmol/l Ca2+), the addition
      of increasing concentrations of nicardipine (200 nmol/l, 2 micromol/l and 20
      micromol/l) decreased single-channel open probability in a concentration
      dependent manner (IC50 0.47 micromol/l). In additional experiments using stripped
      rat distal colonic mucosa mounted in conventional Ussing chambers, serosal
      addition of nicardipine at increasing concentrations (ranging from 200 nmol/l to
      20 micromol/l) produced a concentration-dependent inhibition of dibutyryl-cAMP
      stimulated electrogenic Cl- secretion (IC50 2 micromol/l). Taken together, these
      results indicate that nicardipine has a direct inhibitory action on 23-pS
      basolateral K+ channels in human intestinal crypt cells, which is likely to
      decrease cAMP-stimulated electrogenic Cl- secretion. These basolateral K+
      channels may provide a focal point for the development of new strategies in the
      treatment of secretory diarrhoeal diseases.

PMID- 10089574
TI  - Influence of substrate structure on substrate binding to the renal organic
      cation/H+ exchanger.
AB  - The carrier-mediated exchange of H+ for organic cations ("OC/H+ exchange") is the
      active step in OC secretion in renal proximal tubules. Although hydrophobicity is
      known to be an important criterion for binding of substrates to this transporter,
      the degree to which steric parameters of substrate structure influence binding to
      the exchanger is unclear. We examined this issue by measuring the inhibition of
      OC/H+ exchange produced by a group of quaternary ammonium compounds which share a
      common structural motif: an N1-pyridinium residue. Activity of the OC/H+
      exchanger was determined by measuring transport of [14C]tetraethylammonium (TEA)
      in brush-border membrane vesicles (BBMV) from rabbit renal cortex. Transport was
      measured in the presence of a pH gradient (pHin 6.0; pHout 7.5) to maximize
      TEA/H+ exchange. Apparent inhibitory constants (Ki values) for each test agent
      were measured. The test agents included 4-phenylpyridiniums and 3
      phenylpyridiniums, quinoliniums and acridiniums. The planar structure of these
      compounds permits a direct test of whether the presence of planar hydrophobic
      mass in different orientations relative to the pyridinium motif exerts a
      systematic effect on substrate binding to the OC/H+ exchanger. The hydrophobicity
      of each group of compounds was systematically varied by addition of different
      substituents at the quaternary nitrogen. Whereas decreases in Ki proved to be
      proportional to hydrophobicity, the position of the phenyl-ring substituent(s)
      had no effect on substrate interaction with the exchanger. The results led to the
      development of a preliminary quantitative structure-activity relationship (QSAR)
      correlating substrate hydrophobicity and substrate binding to the OC/H+
      exchanger. This QSAR was used to predict the binding of 1-methyl-4
      phenylpyridinium (MPP+), (+) and (-)nicotine, (+) and (-)ephedrine, quinine and
      quinidine to the OC/H+ exchanger. Molecular graphics representation of the 3D
      structures of the test agents was used to develop a working model of a
      hydrophobic, planar receptor surface on the OC/H+ exchanger against which
      substrates are suggested to interact during binding. Development of the QSAR and
      receptor surface model open the way to quantitative tests of the specific
      physical and structural determinants of substrate selectivity by the renal OC/H+
      exchanger.

PMID- 10089575
TI  - Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells
      susceptible to high urea concentrations.
AB  - Exposure of Madin-Darby canine kidney (MDCK) cells to elevated extracellular NaCl
      concentrations is associated with increased heat shock protein 72 (HSP72)
      expression and improved survival of these pretreated cells upon exposure to an
      additional 600 mM urea in the medium. To establish a causal relationship between
      HSP72 expression and cell protection against high urea concentrations, two
      approaches to inhibit NaCl-induced HSP72 synthesis prior to exposure to 600 mM
      urea were employed. First, the highly specific p38 kinase inhibitor SB203580 was
      added (100 microM) to the hypertonic medium (600 mosm/kg H2O by NaCl addition, 2
      days of exposure), which significantly reduced HSP72 mRNA abundance and HSP72
      content. Survival of these cells after a 24-h urea treatment (600 mM) was
      markedly curtailed compared with appropriate controls. Second, a pcDNA3-based
      construct, containing 322 bases of the HSP72 open reading frame in antisense
      orientation and the geneticine resistance gene, was transfected into MDCK cells.
      Clones with strong inhibition of HSP72 synthesis and others which express the
      protein at normal levels (comparable to nontransfected MDCK cells) after heat
      shock treatment or hypertonic stress were established. When these transformants
      were subjected to hypertonic stress for 2 days prior to exposure to an additional
      600 mM urea for 24 h, cell survival was significantly reduced in those clones in
      which HSP72 expression was strongly inhibited. These results provide further
      evidence for the protective function of HSP72 against high urea concentrations in
      renal epithelial cells.

PMID- 10089576
TI  - Distribution of oxygen tension on the surface of arterioles, capillaries and
      venules of brain cortex and in tissue in normoxia: an experimental study on rats.
AB  - The distribution of oxygen tension (PO2) was studied in normoxia on the surface
      of arterioles, capillaries and venules of rat brain cortex, both longitudinally
      and in tissue radially from the wall of microvessels. Along the arteriolar tree,
      PO2 decreased from 81.2+/-6. 2 mmHg (mean+/-SD) on 1 degrees A (first-order
      branch) arterioles to 61.5+/-12 mmHg on 5 degrees A arterioles. Transmural flux
      of oxygen from blood to tissue increased markedly at the level of minute 4
      degrees A-5 degrees A arterioles. At the arterial end of cortical capillaries,
      PO2 averaged 57.9+/-10.6 mmHg, n=19, (or, in terms of blood oxygen saturation
      SO2; 82+/-9%) and 258+/-19 microm downstream 40.9+/-11.5 mmHg, n=19, (SO2 59+/
      18%). The averaged PO2 drop on the capillaries studied was 17+/-9 mmHg, and the
      longitudinal PO2 gradient was accordingly 0.07+/-0.04 mmHg/ microm (SO2 0.1+/
      0.06%/ microm). The radial profiles of tissue PO2 recorded near arterioles,
      capillaries and venules clearly demonstrated that all these microvessels supply
      oxygen to brain tissue. The PO2 distribution on venules was characterized by
      pronounced heterogeneity.

PMID- 10089578
TI  - Microdissection-Based p53 Genotyping: Concepts for Molecular Testing.
AB  - p53 is the most commonly altered tumor-suppressor gene in humans, involved in the
      development and progression of many diverse forms of human cancer. Although much
      remains to be learned about the biology of this important growth regulatory gene,
      sufficient experience has been accumulated with respect to the occurrence and
      pattern of p53 mutational change to justify molecular diagnostic testing for
      specific objectives. The authors outline specific concepts for testing with
      particular emphasis for solid tumor molecular diagnostics. This article focuses
      on microdissection-based fixed tissue molecular analysis, introducing new
      considerations related to quality control appropriate for this type of
      methodology. Given the rapidly evolving nature of molecular genetics, the
      suggestions provided here should be viewed as flexible. Nevertheless, the
      concepts are intended to serve as a model for other oncogene/tumor suppressor
      gene assays to be developed with the overall purpose of establishing informative
      integrated histopathologic/genetic molecular diagnostic testing to complement
      standard microscopic analysis.

PMID- 10089577
TI  - The biological zero signal in laser Doppler fluximetry - origins and practical
      implications.
AB  - This study seeks to identify the origin of the signal, known as biological zero,
      that is obtained using laser Doppler fluximetry when flow is arrested. It makes
      specific recommendations on how this signal should be measured and handled when
      undertaking flow studies. The experiments undertaken using flow models, animal
      and human tissue, organ preparations and human subjects showed that, although
      there may be contributions to the no-flow laser Doppler signal from vasomotion,
      Brownian motion from within the vascular compartment and the effects of cuff
      compression, the predominant contribution is from Brownian motion arising from
      the interstitial compartment. The biological zero signal is additive to the flow
      signal providing conditions within the interstitium remain constant with changes
      in blood flow. It is thus concluded that the biological zero signal arises from
      Brownian motion of the macro molecules within the interstitium. This signal
      should be obtained following 3-5 min of cuff occlusion with inflation applied
      rapidly with the smallest cuff that is compatible with flow arrest. Biological
      zero should be measured under each experimental condition and subtracted from the
      flow signal.

PMID- 10089579
TI  - Traditional African medicine in dermatology: complementary medical practices from
      east Africa and "guboow".

PMID- 10089580
TI  - Traditional Arabic medicine in dermatology.

PMID- 10089581
TI  - Traditional Chinese medicine in dermatology.

PMID- 10089582
TI  - Traditional Korean medicine in dermatology.

PMID- 10089583
TI  - Traditional Iberian folk medicine in dermatology.

PMID- 10089584
TI  - Traditional Indian medicine in dermatology.

PMID- 10089585
TI  - Traditional Native American medicine in dermatology.

PMID- 10089586
TI  - The American system of medicine.

PMID- 10089587
TI  - Nutritional dermatology.

PMID- 10089588
TI  - Homeopathy in dermatology.

PMID- 10089589
TI  - Placebo therapy in dermatology.

PMID- 10089590
TI  - Reflex therapy in dermatology.

PMID- 10089591
TI  - Traditional approaches to wound healing.

PMID- 10089592
TI  - Complementary and alternative medicine and the NIH.

PMID- 10089593
TI  - Investigation into PCB biodegradation using uniformly 14C-labelled
      dichlorobiphenyl.
AB  - Biodegradation of polychlorinated biphenyls (PCBs) in soil is considered to be
      very complex due to various physico-chemical factors involved. Isotope labelling
      technique is the best to trace fate of the xenobiotic in the environment. In this
      work, the uniformly 14C-labelled PCB congener 11 (3,3'-chlorobiphenyl) was chosen
      as a low chlorinated coplanar biphenyl which was assumed to be readily degraded
      by microorganisms. Pleurotus ostreatus and two Pseudomonas species, representing
      white rot fungi and soil bacteria were used separately or in a consortium. The
      amount of liberated 14CO2 and radio-HPLC, HPLC, GC-MS, and radio-TLC analyses of
      extracts at the end of a two-month experiment showed that the mineralization of
      PCB 11 was < 0.4%, volatilization < 3.1%, and 30% of radioactivity was
      irreversibly bound to the soil matrix. The respective contents of all
      intermediate metabolites were 4.7 to 10.5 and 2.5 to 2.7% where Pseudomonas
      alcaligenes alone or in combination with P. putida was applied. 3-Chlorobenzoic
      acid was the major biodegradation product.

PMID- 10089595
TI  - A simple high-performance liquid chromatography assay for the major cisapride
      metabolite, norcisapride, in human urine.
AB  - A simple high-performance liquid chromatography assay using fluorescence
      detection for the major metabolite of the gastric prokinetic drug cisapride,
      norcisapride, is presented. Analysis is performed using an Alltech Platinum EPS
      C8 column with a mobile phase made up of methanol and 0.02M sodium dihygrogen
      phosphate (45:55, v/v) containing triethylamine (1 g/L). Complete resolution is
      achieved among norcisapride, the internal standard (metoclopramide), and
      endogenous urinary components. The assay is linear over the range 50-2000 ng/mL
      with a mean recovery of 71.2% across the analytical range following solvent
      extraction with toluene-isoamyl alcohol (95:5, v/v). Intraday coefficients of
      variation (precision) determined at 200 and 1000 ng/mL are 6.0 and 9.8%,
      respectively, and interday coefficients of variation are 8.8 and 6.6%,
      respectively. Intra- and interassay accuracy (as mean relative error) determined
      at the same concentrations is within 10% in all cases. An analysis of urine
      samples from a healthy volunteer following the administration of a single 10-mg
      oral dose of cisapride is shown.

PMID- 10089594
TI  - Decommissioning of a nuclear power plant: determination of site-specific sorption
      coefficients for Co-60 and Cs-137.
AB  - Assessment of radiological risks in strategies for decommissioning of nuclear
      installations have to consider not only technical concepts such as cutting and
      decontamination techniques but, even more important, requirements for input of
      reliable information on the hydrological situation and retardation capabilities
      of relevant radionuclides specific to the respective decommissioning operation.
      In this paper we describe appropriate methods for obtaining site-specific
      sorption data and present results achieved from a case study performed as a
      commercial contractual work preliminary to the planned decommissioning of a
      nuclear power plant. A detailed mineralogical study of the sediment used in our
      sorption experiment highlights the necessity of a thorough sample homogenization
      and characterization. Batch experiments using radiotracer techniques for the
      determination of site-specific sorption coefficients show significant retardation
      for Co-60 and Cs-137 after only 2 h of equilibration between the preconditioned
      groundwater and sediment. Sorption is more effective in the groundwater of a
      deeper aquifer containing a higher amount of colloidal clay (illite) particles <
      0.63 micron. The Co-60 radiotracer is more completely sorbed than the Cs-137
      radiotracer. Equilibration of radionuclide distribution is slow, particularly for
      Co-60. Presence of EDTA reduces sorption of Co-60 efficiently while Cs-137
      sorption remains unaffected.

PMID- 10089596
TI  - High-performance liquid chromatography column switching applied to the trace
      determination of herbicides in environmental and drinking water samples.
AB  - A selective and sensitive coupled-column high-performance liquid chromatographic
      method is developed for the simultaneous determination of 5 phenylurea herbicides
      (monuron, linuron, isoproturon, monolinuron, and diuron) in environmental and
      drinking water samples. Sample clean-up is performed automatically by means of a
      column switching technique. Using 2 octadecyl silica columns connected via two
      programmable 6-port valves and ultraviolet detection at 244 nm, the
      aforementioned compounds can be determined at the low concentration levels
      required for pesticide residue analysis in water samples. A mobile phase
      consisting of a mixture of methanol-water (55:45, v/v) is pumped at 1 mL/min. For
      the 5 phenylureas, high recoveries ranging from 94.9 to 101.6%, good
      reproducibility with relative standard deviations lower than 5%, and wide linear
      ranges up to 20 micrograms/L are observed with determination limits of 0.05
      microgram/L. The method is successfully applied to the screening of different
      environmental water samples such as surface, ground, rain, and drinking water.

PMID- 10089597
TI  - Simple and sensitive analysis of nereistoxin and its metabolites in human serum
      using headspace solid-phase microextraction and gas chromatography-mass
      spectrometry.
AB  - A simple method for the analysis of nereistoxin and its metabolites in human
      serum using headspace solid-phase microextraction (SPME) and gas chromatography
      mass spectrometry (GC-MS) is developed. A vial containing a serum sample, 5M
      sodium hydroxide, and benzylacetone (internal standard) is heated to 70 degrees
      C, and an SPME fiber is exposed for 30 min in the headspace of the vial. The
      compounds extracted by the fiber are desorbed by exposing the fiber in the
      injection port of the GC-MS. The calibration curves show linearity in the range
      of 0.05-5.0 micrograms/mL for nereistoxin and N-methyl-N-(2-methylthio-1
      methylthiomethyl)ethylamine, 0.01-5.0 micrograms/mL for S,S'-dimethyl
      dihydronereistoxin, and 0.5-10 micrograms/mL for 2-methylthio-1
      methylthiomethylethylamine in serum. No interferences are found, and the analysis
      time is 50 min for one sample. In addition, this proposed method is applied to a
      patient who attempted suicide by ingesting Padan 4R, a herbicide. Padan 4R
      contains 4% cartap hydrochloride, which is an analogue of nereistoxin.
      Nereistoxin and its metabolites are detected in the serum samples collected from
      the patient during hospitalization. The concentration ranges of nereistoxin in
      the serum are 0.09-2.69 micrograms/mL.

PMID- 10089598
TI  - Acoustics of children's speech: developmental changes of temporal and spectral
      parameters.
AB  - Changes in magnitude and variability of duration, fundamental frequency, formant
      frequencies, and spectral envelope of children's speech are investigated as a
      function of age and gender using data obtained from 436 children, ages 5 to 17
      years, and 56 adults. The results confirm that the reduction in magnitude and
      within-subject variability of both temporal and spectral acoustic parameters with
      age is a major trend associated with speech development in normal children.
      Between ages 9 and 12, both magnitude and variability of segmental durations
      decrease significantly and rapidly, converging to adult levels around age 12.
      Within-subject fundamental frequency and formant-frequency variability, however,
      may reach adult range about 2 or 3 years later. Differentiation of male and
      female fundamental frequency and formant frequency patterns begins at around age
      11, becoming fully established around age 15. During that time period, changes in
      vowel formant frequencies of male speakers is approximately linear with age,
      while such a linear trend is less obvious for female speakers. These results
      support the hypothesis of uniform axial growth of the vocal tract for male
      speakers. The study also shows evidence for an apparent overshoot in acoustic
      parameter values, somewhere between ages 13 and 15, before converging to the
      canonical levels for adults. For instance, teenagers around age 14 differ from
      adults in that, on average, they show shorter segmental durations and exhibit
      less within-subject variability in durations, fundamental frequency, and spectral
      envelope measures.

PMID- 10089599
TI  - Prediction of conductive hearing loss based on acoustic ear-canal response using
      a multivariate clinical decision theory.
AB  - This study evaluated the accuracy of acoustic response tests in predicting
      conductive hearing loss in 161 ears of subjects from the age of 2 to 10 yr, using
      as a "gold standard" the air-bone gap to classify ears as normal or impaired. The
      acoustic tests included tympanometric peak-compensated static admittance
      magnitude (SA) and tympanometric gradient at 226 Hz, and admittance-reflectance
      (YR) measurements from 0.5 to 8 kHz. The performance of individual, frequency
      specific, YR test variables as predictors was assessed. By applying logistic
      regression (LR) and discriminant analysis (DA) techniques to the multivariate YR
      response, two univariate functions were calculated as the linear combinations of
      YR variables across frequency that best separated normal and impaired ears. The
      tympanometric and YR tests were also combined in a multivariate manner to test
      whether predictive efficacy improved when 226-Hz tympanometry was added to the
      predictor set. Conductive hearing loss was predicted based on air-bone gap
      thresholds at 0.5 and 2 kHz, and on a maximum air-bone gap at any octave
      frequency from 0.5 to 4 kHz. Each air-bone gap threshold ranged from 5 to 30 dB
      in 5-dB steps. Areas under the relative operating characteristic curve for DA and
      LR were larger than for reflectance at 2 kHz, SA and Gr. For constant hit rates
      of 80% and 90%, both DA and LR scores had lower false-alarm rates than
      tympanometric tests-LR achieved a false-alarm rate of 6% for a sensitivity of
      90%. In general, LR outperformed DA as the multivariate technique of choice. In
      predicting an impairment at 0.5 kHz, the reflectance scores at 0.5 kHz were less
      accurate predictors than reflectance at 2 and 4 kHz. This supports the hypothesis
      that the 2-4-kHz range is a particularly sensitive indicator of middle-ear
      status, in agreement with the spectral composition of the output predictor from
      the multivariate analyses. When tympanometric and YR tests were combined, the
      resulting predictor performed slightly better or the same as the predictor
      calculated from the use of the YR test alone. The main conclusion is that these
      multivariate acoustic tests of the middle ear, which are analyzed using a
      clinical decision theory, are effective predictors of conductive hearing loss.

PMID- 10089600
TI  - Strategies used to detect auditory signals in small sets of random maskers.
AB  - Detection performance for a masked auditory signal of fixed frequency can be
      substantially degraded if there is uncertainty about the frequency content of the
      masker. A quasimolecular psychophysical approach was used to examine response
      strategies in masker-uncertainty conditions, and to investigate the influence of
      uncertainty when the number of different masker samples was limited to ten or
      fewer. The task of the four listeners was to detect a 1000-Hz signal that was
      presented simultaneously with one of ten ten-tone masker samples. The masker
      sample was either fixed throughout a block of two-interval forced-choice trials
      or was randomized across or within trials. The primary results showed that: (1)
      When the signal level was low and the masker sample differed between the two
      intervals of a trial, most listeners based their responses more on the presence
      of specific masker samples than on the signal. (2) The detrimental effect of
      masker uncertainty was clearly evident when only four maskers were randomly
      presented, and grew as the size of the masker set was increased from two to ten.
      (3) The slopes of psychometric functions measured with the same masker samples
      differed among the fixed and two random-masker conditions. (4) There were large
      differences in the influence of masker uncertainty across masker samples and
      listeners. These data demonstrate the great susceptibility of human listeners to
      the influence of masker uncertainty and the ability of quasimolecular
      investigations to reveal important aspects of behavior in uncertainty condition.

PMID- 10089601
TI  - The effects of signal duration on NoSo and NoS pi thresholds at 500 Hz and 4 kHz.
AB  - A two-interval, two-alternative temporal forced-choice procedure was used to
      measure NoSo and NoS pi masked thresholds with 500-Hz and 4-kHz tonal signals.
      The duration of the signal was either 10, 20, 40, or 320 ms. The maskers were 200
      Hz-wide bands of Gaussian noise centered at the frequency of the signal and
      presented continuously. Decreasing the duration of the 500-Hz tonal signal
      resulted in a modest increase (1.5 dB or so) in the masking-level difference
      (MLD) measured between NoSo and NoS pi conditions. In contrast, decreasing the
      duration of the 4-kHz tonal signal resulted in a substantial decrease (4.5 dB or
      so) in the MLD. Comparisons of the data with thresholds predicted from analyses
      based on "windows of temporal integration" provided quantitatively acceptable
      accounts of the data. The data obtained in the NoS pi condition at 4 kHz, which
      are novel and were of primary interest, were well-accounted for in a statistical
      sense. However, there were small, but systematic, discrepancies between the
      predictions and the data. Those discrepancies, although small in magnitude,
      suggest that binaural temporal integration at high frequencies, where the
      envelopes of the stimuli convey the information, may be inherently different from
      both monaural temporal integration and binaural temporal integration at low
      frequencies.

PMID- 10089602
TI  - A signal detection analysis of auditory-frequency discrimination in the rat.
AB  - The frequency-discrimination behavior of rats in a simple go/no-go task was
      analyzed using the theory of signal detection. Discrimination acuity was studied
      and the receiver operating characteristic (ROC) was generated in subjects by
      varying the reinforcement schedule and signal probability. The detectability
      indices d', A', and sensitivity index (SI) and response-bias indices B" and
      responsivity index (RI) were used to describe behavior. A' gave the most suitable
      psychometric functions while RI best described response-bias behavior. Weber
      ratios were 6.25% +/- 0.23% at 5 kHz in three subjects. The best method to obtain
      the ROC was to vary the probability with which subjects were reinforced. The ROC
      in two subjects demonstrated classical forms; in another subject, the function
      was asymmetric to the extent that detectability was not independent of response
      bias. Subjects altered their decision criterion in reporting a signal from trial
      to trial depending on previous trial events. On any given trial, subjects made a
      decision in one of several "decision states." Variables that influenced decision
      states included previous reinforcement and timeouts. The data indicate that
      timeouts may not be a useful feature in go/no-go tasks. The identification of
      multiple-decision states within a single behavioral session is a convenient
      method to generate the ROC without expressly manipulating experimental
      conditions.

PMID- 10089603
TI  - Importance of temporal-envelope cues in consonant recognition.
AB  - The role of different modulation frequencies in the speech envelope were studied
      by means of the manipulation of vowel-consonant-vowel (VCV) syllables. The
      envelope of the signal was extracted from the speech and the fine-structure was
      replaced by speech-shaped noise. The temporal envelopes in every critical band of
      the speech signal were notch filtered in order to assess the relative importance
      of different modulation frequency regions between 0 and 20 Hz. For this purpose
      notch filters around three center frequencies (8, 12, and 16 Hz) with three
      different notch widths (4-, 8-, and 12-Hz wide) were used. These stimuli were
      used in a consonant-recognition task in which ten normal-hearing subjects
      participated, and their results were analyzed in terms of recognition scores.
      More qualitative information was obtained with a multidimensional scaling method
      (INDSCAL) and sequential information analysis (SINFA). Consonant recognition is
      very robust for the removal of certain modulation frequency areas. Only when a
      wide notch around 8 Hz is applied does the speech signal become heavily degraded.
      As expected, the voicing information is lost, while there are different effects
      on plosiveness and nasality. Even the smallest filtering has a substantial effect
      on the transfer of the plosiveness feature, while on the other hand, filtering
      out only the low-modulation frequencies has a substantial effect on the transfer
      of nasality cues.

PMID- 10089604
TI  - Sound localization in noise in normal-hearing listeners.
AB  - The ability to localize a click train in the frontal-horizontal plane was
      measured in quiet and in the presence of a white-noise masker. The experiment
      tested the effects of signal frequency, signal-to-noise ratio (S/N), and masker
      location. Clicks were low-pass filtered at 11 kHz in the broadband condition, low
      pass filtered at 1.6 kHz in the low-pass condition, and bandpass filtered between
      1.6 and 11 kHz in the high-pass condition. The masker was presented at either 
      90, 0, or +90 deg azimuth. Six signal-to-noise ratios were used, ranging from -9
      to +18 dB. Results obtained with four normal-hearing listeners show that (1) for
      all masker locations and filtering conditions, localization accuracy remains
      unaffected by noise until 0-6 dB S/N and decreases at more adverse signal-to
      noise ratios, (2) for all filtering conditions and at low signal-to-noise ratios,
      the effect of noise is greater when noise is presented at +/- 90 deg azimuth than
      at 0 deg azimuth, (3) the effect of noise is similar for all filtering conditions
      when noise is presented at 0 deg azimuth, and (4) when noise is presented at +/-
      90 deg azimuth, the effect of noise is similar for the broadband and high-pass
      conditions, but greater for the low-pass condition. These results suggest that
      the low- and high-frequency cues used to localize sounds are equally affected
      when noise is presented at 0 deg azimuth. However, low-frequency cues are less
      resistant to noise than high-frequency cues when noise is presented at +/- 90 deg
      azimuth. When both low- and high-frequency cues are available, listeners base
      their decision on the cues providing the most accurate estimation of the
      direction of the sound source (high-frequency cues). Parallel measures of click
      detectability suggest that the poorer localization accuracy observed when noise
      is at +/- 90 deg azimuth may be caused by a reduction in the detectability of the
      signal at the ear ipsilateral to the noise.

PMID- 10089605
TI  - Nonsense-syllable recognition in noise using monaural and binaural listening
      strategies.
AB  - Using a binaurally equipped KEMAR manikin, syllables of the CUNY Nonsense
      Syllable Test were recorded in sound field at 0-degree azimuth against a
      background of cafeteria noise at 270-degrees azimuth, at several signal-to-noise
      (S/N) ratios. The combination of inputs recorded at each ear was delivered to ten
      normal-hearing (NH) and eight sensorineurally hearing impaired (HI) listeners
      through insert ear phones to produce five experimental listening conditions: (1)
      binaural head shadow (HS), in which ear presentation was analogous to the
      original stimulus recording, (2) binaural favorable (BF), in which the noise
      shadowed (right-ear) recording was presented to both ears, (3) monaural favorable
      (MF), in which the noise-shadowed recording was presented only to the right ear,
      (4) monoaural unfavorable (MU), in which the noise-unshadowed (left ear)
      recording was presented only to the left ear, and (5) simulated monoaural aided
      (SMA), in which the noise-shadowed recording was presented to the right ear and
      the noise-unshadowed recording--attenuated by 20 dB relative to the HS condition-
      was presented to the left ear. All main effects (subject type, listening
      condition, and S/N ratio) were statistically significant. Normal listeners showed
      3.3- and 3.2-dB advantages, respectively, due to head-shadow and binaural
      squelch, over hearing-impaired listeners. Some hearing-impaired listeners
      performed better under the SMA or BF conditions than under the HS condition.
      Potential digital signal processing strategies designed to optimize speech
      understanding under binaurally aided listening conditions are discussed.

PMID- 10089606
TI  - Level discrimination of single tones in a multitone complex by normal-hearing and
      hearing-impaired listeners.
AB  - A conditional-on-a-single-stimulus (COSS) analysis procedure [B. G. Berg, J.
      Acoust. Soc. Am. 86, 1743-1746 (1989)] was used to estimate how well normal
      hearing and hearing-impaired listeners selectively attend to individual spectral
      components of a broadband signal in a level discrimination task. On each trial,
      two multitone complexes consisting of six octave frequencies from 250 to 8000 Hz
      were presented to listeners. The levels of the individual tones were chosen
      independently and at random on each presentation. The target tone was selected,
      within a block of trials, as the 250-, 1000-, or 4000-Hz component. On each
      trial, listeners were asked to indicate which of the two complex sounds contained
      the higher level target. As a group, normal-hearing listeners exhibited greater
      selectivity than hearing-impaired listeners to the 250-Hz target, while hearing
      impaired listeners showed greater selectivity than normal-hearing listeners to
      the 4000-Hz target, which is in the region of their hearing loss. Both groups of
      listeners displayed large variability in their ability to selectively weight the
      1000-Hz target. Trial-by-trial analysis showed a decrease in weighting efficiency
      with increasing frequency for normal-hearing listeners, but a relatively constant
      weighting efficiency across frequency for hearing-impaired listeners.
      Interestingly, hearing-impaired listeners selectively weighted the 4000-Hz
      target, which was in the region of their hearing loss, more efficiently than did
      the normal-hearing listeners.

PMID- 10089607
TI  - Gap detection by early-deafened cochlear-implant subjects.
AB  - Two studies investigating gap-detection thresholds were conducted with cochlear
      implant subjects whose onset of profound hearing loss was very early in life. The
      Cochlear Limited multiple-electrode prosthesis was used. The first study
      investigated the effects of pulse rate (200, 500, and 1000 pulses/s) and stimulus
      duration (500 and 1000 ms) on gap thresholds in 15 subjects. Average gap
      thresholds were 1.8 to 32.1 ms. There was essentially no effect of pulse rate and
      for almost all subjects, no effect of stimulus duration. For two subjects,
      performance was poorer for the 1000-ms stimulus duration. The second study
      investigated the relationships between gap thresholds, subject variables, and
      speech-perception scores. Data from the first study were combined with those from
      previous studies [Busby et al., Audiology 31, 95-111 (1992); Tong et al., J.
      Acoust. Soc. Am. 84, 951-962 (1988)], providing data from 27 subjects. A
      significant negative correlation was found between age at onset of deafness and
      gap thresholds and most variability in gap thresholds was for the congenitally
      deaf subjects. Significant negative correlations were found between gap
      thresholds and word scores for open-set Bamford-Kowal-Bench (BKB) sentences in
      the auditory-visual condition and lipreading enhancement scores for the same
      test.

PMID- 10089608
TI  - Temporal mechanisms underlying recovery from forward masking in multielectrode
      implant listeners.
AB  - This paper describes a detailed study of recovery from forward masking in six
      users of the Nucleus-22 cochlear implant with a range of performance in speech
      recognition tests. Recovery from a 300-ms-long pulse train presented at 1000 pps
      was found to be fastest in the poorer performers. The shape of the recovery
      function was found to be most strongly influenced by masker duration, suggesting
      that temporal integration plays a prominent role in recovery from forward
      masking. The recovery functions are reasonably well described by a sum of two
      exponentially decaying processes. Their relative weights depend on the amount of
      temporal integration occurring during the masker, and show strong intersubject
      variability. Nonmonotonicities sometimes observed in the recovery functions may
      be accounted for by considering the influence of neural adaptation.

PMID- 10089609
TI  - Interarticulator programming in VCV sequences: lip and tongue movements.
AB  - This study examined the temporal phasing of tongue and lip movements in vowel
      consonant-vowel sequences where the consonant is a bilabial stop consonant /p, b/
      and the vowels one of /i, a, u/; only asymmetrical vowel contexts were included
      in the analysis. Four subjects participated. Articulatory movements were recorded
      using a magnetometer system. The onset of the tongue movement from the first to
      the second vowel almost always occurred before the oral closure. Most of the
      tongue movement trajectory from the first to the second vowel took place during
      the oral closure for the stop. For all subjects, the onset of the tongue movement
      occurred earlier with respect to the onset of the lip closing movement as the
      tongue movement trajectory increased. The influence of consonant voicing and
      vowel context on interarticulator timing and tongue movement kinematics varied
      across subjects. Overall, the results are compatible with the hypothesis that
      there is a temporal window before the oral closure for the stop during which the
      tongue movement can start. A very early onset of the tongue movement relative to
      the stop closure together with an extensive movement before the closure would
      most likely produce an extra vowel sound before the closure.

PMID- 10089610
TI  - Pitch accent in spoken-word recognition in Japanese.
AB  - Three experiments addressed the question of whether pitch-accent information may
      be exploited in the process of recognizing spoken words in Tokyo Japanese. In a
      two-choice classification task, listeners judged from which of two words,
      differing in accentual structure, isolated syllables had been extracted (e.g., ka
      from baka HL or gaka LH); most judgments were correct, and listeners' decisions
      were correlated with the fundamental frequency characteristics of the syllables.
      In a gating experiment, listeners heard initial fragments of words and guessed
      what the words were; their guesses overwhelmingly had the same initial accent
      structure as the gated word even when only the beginning CV of the stimulus
      (e.g., na- from nagasa HLL or nagashi LHH) was presented. In addition, listeners
      were more confident in guesses with the same initial accent structure as the
      stimulus than in guesses with different accent. In a lexical decision experiment,
      responses to spoken words (e.g., ame HL) were speeded by previous presentation of
      the same word (e.g., ame HL) but not by previous presentation of a word differing
      only in accent (e.g., ame LH). Together these findings provide strong evidence
      that accentual information constrains the activation and selection of candidates
      for spoken-word recognition.

PMID- 10089611
TI  - Recognition of spectrally degraded and frequency-shifted vowels in acoustic and
      electric hearing.
AB  - The present study measured the recognition of spectrally degraded and frequency
      shifted vowels in both acoustic and electric hearing. Vowel stimuli were passed
      through 4, 8, or 16 bandpass filters and the temporal envelopes from each filter
      band were extracted by half-wave rectification and low-pass filtering. The
      temporal envelopes were used to modulate noise bands which were shifted in
      frequency relative to the corresponding analysis filters. This manipulation not
      only degraded the spectral information by discarding within-band spectral detail,
      but also shifted the tonotopic representation of spectral envelope information.
      Results from five normal-hearing subjects showed that vowel recognition was
      sensitive to both spectral resolution and frequency shifting. The effect of a
      frequency shift did not interact with spectral resolution, suggesting that
      spectral resolution and spectral shifting are orthogonal in terms of
      intelligibility. High vowel recognition scores were observed for as few as four
      bands. Regardless of the number of bands, no significant performance drop was
      observed for tonotopic shifts equivalent to 3 mm along the basilar membrane, that
      is, for frequency shifts of 40%-60%. Similar results were obtained from five
      cochlear implant listeners, when electrode locations were fixed and the spectral
      location of the analysis filters was shifted. Changes in recognition performance
      in electrical and acoustic hearing were similar in terms of the relative location
      of electrodes rather than the absolute location of electrodes, indicating that
      cochlear implant users may at least partly accommodate to the new patterns of
      speech sounds after long-time exposure to their normal speech processor.

PMID- 10089612
TI  - Segmental and syllabic representations in the perception of speech by young
      infants.
AB  - In a series of four experiments, the ability of 3- to 4-month-old infants to form
      categorical representations to syllable-initial consonants in monosyllabic
      stimuli (experiments 1 and 2) and to initial and final syllables in bisyllabic
      stimuli (experiments 3 and 4, respectively) was investigated. Experiment 1
      yielded no evidence of categorical representations for the initial consonant.
      However, the results indicated that the four or six stimuli presented during the
      initial phase of familiarization had been remembered. The results of experiment
      2, which employed a less stringent familiarization criterion, replicated the
      findings of experiment 1, although there was some evidence for categorization for
      infants whose familiarization performance more closely matched the weaker
      criterion. In experiment 3, there was strong evidence for a categorical
      representation of the initial syllable of bisyllabic stimuli for infants
      experiencing six familiar stimuli. In experiment 4, there was less robust
      evidence of categorization of the final syllable of bisyllabic stimuli, but again
      only when six familiar stimuli were experienced. The results were discussed in
      terms of the earliest representation of speech being syllables that could be
      modified by the rhythmic nature of the infant's native language.

PMID- 10089613
TI  - Fractal dimensions of speech sounds: computation and application to automatic
      speech recognition.
AB  - The dynamics of airflow during speech production may often result in some small
      or large degree of turbulence. In this paper, the geometry of speech turbulence
      as reflected in the fragmentation of the time signal is quantified by using
      fractal models. An efficient algorithm for estimating the short-time fractal
      dimension of speech signals based on multiscale morphological filtering is
      described, and its potential for speech segmentation and phonetic classification
      discussed. Also reported are experimental results on using the short-time fractal
      dimension of speech signals at multiple scales as additional features in an
      automatic speech-recognition system using hidden Markov models, which provide a
      modest improvement in speech-recognition performance.

PMID- 10089614
TI  - Computer identification of musical instruments using pattern recognition with
      cepstral coefficients as features.
AB  - Cepstral coefficients based on a constant Q transform have been calculated for 28
      short (1-2 s) oboe sounds and 52 short saxophone sounds. These were used as
      features in a pattern analysis to determine for each of these sounds comprising
      the test set whether it belongs to the oboe or to the sax class. The training set
      consisted of longer sounds of 1 min or more for each of the instruments. A k
      means algorithm was used to calculate clusters for the training data, and
      Gaussian probability density functions were formed from the mean and variance of
      each of the clusters. Each member of the test set was then analyzed to determine
      the probability that it belonged to each of the two classes; and a Bayes decision
      rule was invoked to assign it to one of the classes. Results have been extremely
      good and are compared to a human perception experiment identifying a subset of
      these same sounds.

PMID- 10089615
TI  - Effects of subglottal pressure variation on professional baritone singers' voice
      sources.
AB  - Five professional operatic baritone singers' voice-source characteristics were
      analyzed by means of inverse filtering of the flow signal as captured by a flow
      mask. The subjects sang a long sustained diminuendo, from loudest to softest,
      three times on the vowels [a:] and [ae:] at fundamental frequencies representing
      25%, 50%, and 75% of their total pitch range as measured in semitones. During the
      diminuendos, they repeatedly inserted the consonant [p] so that associated
      subglottal pressures could be estimated from the oral pressure during the p
      occlusions. Pooling the three takes of each condition, ten subglottal pressures,
      equidistantly spaced between highest and lowest, were selected for analysis.
      Sound-pressure levels (SPL), peak-to-peak glottal airflow, maximum flow
      declination rate, closed quotient, glottal dc flow, and the level difference
      between the two lowest partials of the source spectrum (H1-H2) were determined.
      All parameters except the glottal dc flow showed a systematic variation with
      subglottal pressure or the fractional excess pressure over threshold. The results
      are given in terms of equations representing the average across subjects for the
      relation between subglottal pressure and each of the mentioned voice-source
      parameters.

PMID- 10089616
TI  - A microcosm of musical expression: II. Quantitative analysis of pianists'
      dynamics in the initial measures of Chopin's Etude in E major.
AB  - Patterns of expressive dynamics were measured in bars 1-5 of 115 commercially
      recorded performances of Chopin's Etude in E major, op. 10, No. 3. The grand
      average pattern (or dynamic profile) was representative of many performances and
      highly similar to the average dynamic profile of a group of advanced student
      performances, which suggests a widely shared central norm of expressive dynamics.
      The individual dynamic profiles were subjected to principal components analysis,
      which yielded Varimax-rotated components, each representing a different,
      nonstandard dynamic profile associated with a small subset of performances. Most
      performances had dynamic patterns resembling a mixture of several components, and
      no clustering of of performances into distinct groups was apparent. Some weak
      relationships of dynamic profiles with sociocultural variables were found, most
      notably a tendency of female pianists to exhibit a greater dynamic range in the
      melody. Within the melody, there were no significant relationships between
      expressive timing [Repp, J. Acoust. Soc. Am. 104, 1085-1100 (1998)] and
      expressive dynamics. These two important dimensions seemed to be controlled
      independently at this local level and thus offer the artist many degrees of
      freedom in giving a melody expressive shape.

PMID- 10089617
TI  - Shock wave-inertial microbubble interaction: methodology, physical
      characterization, and bioeffect study.
AB  - A method of generating in situ shock wave-inertial microbubble interaction by a
      modified electrohydraulic shock wave lithotripter is proposed and tested in
      vitro. An annular brass ellipsoidal reflector (thickness = 28 mm) that can be
      mounted on the aperture rim of a Dornier XL-1 lithotripter was designed and
      fabricated. This ring reflector shares the same foci with the XL-1 reflector, but
      is 15 mm short in major axis. Thus, a small portion of the spherical shock wave,
      generated by a spark discharge at the first focus (F1) of the reflector, is
      reflected and diffracted by the ring reflector, producing a weak shock wave
      approximately 8.5 microseconds in front of the lithotripter pulse. Based on the
      configuration of the ring reflector (different combinations of six identical
      segments), the peak negative pressure of the preceding weak shock wave at the
      second focus (F2) can be adjusted from -0.96 to -1.91 MPa, at an output voltage
      of 25 kV. The preceding shock wave induces inertial microbubbles, most of which
      expand to a maximum size of 100-200 microns, with a few expanding up to 400
      microns before being collapsed in situ by the ensuing lithotripter pulse.
      Physical characterizations utilizing polyvinylidene difluoride (PVDF) membrane
      hydrophone, high-speed shadowgraph imaging, and passive cavitation detection have
      shown strong secondary shock wave emission immediately following the propagating
      lithotripter shock front, and microjet formation along the wave propagation
      direction. Using the modified reflector, injury to mouse lymphoid cells is
      significantly increased at high exposure (up to 50% with shock number > 100).
      With optimal pulse combination, the maximum efficiency of shock wave-induced
      membrane permeabilization can be enhanced substantially (up to 91%), achieved at
      a low exposure of 50 shocks. These results suggest that shock wave-inertial
      microbubble interaction may be used selectively to either enhance the efficiency
      of shock wave-mediated macromolecule delivery at low exposure or tissue
      destruction at high exposure.

PMID- 10089618
TI  - Effects of deafening on the calls and warble song of adult budgerigars
      (Melopsittacus undulatus).
AB  - Budgerigars are small Australian parrots that learn new vocalizations throughout
      adulthood. Earlier work has shown that an external acoustic model and auditory
      feedback are necessary for the development of normal contact calls in this
      species. Here, the role of auditory feedback in the maintenance of species
      typical contact calls and warble song in adult budgerigars is documented.
      Deafened adult birds (five male, one female) vocalized less frequently and showed
      both suprasegmental and segmental changes in their contact calls and warble song.
      Contact calls of all adult-deafened budgerigars showed abnormalities in acoustic
      structure within days to a few weeks following surgery. Within 6 months of
      surgery, nearly all contact calls produced by deafened birds were strikingly
      abnormal, showing highly variable patterns of frequency modulation and duration.
      The warble song of deafened male budgerigars also differed significantly from
      that of normal budgerigars on several acoustic measures. These results show that
      auditory feedback is necessary for the maintenance of a normal, species-typical
      vocal repertoire in budgerigars.

PMID- 10089619
TI  - Modeling the role of nonhuman vocal membranes in phonation.
AB  - Although the mammalian larynx exhibits little structural variation compared to
      sound-producing organs in other taxa (birds or insects), there are some
      morphological features which could lead to significant differences in acoustic
      functioning, such as air sacs and vocal membranes. The vocal membrane (or "vocal
      lip") is a thin upward extension of the vocal fold that is present in many bat
      and primate species. The vocal membrane was modeled as an additional geometrical
      element in a two-mass model of the larynx. It was found that vocal membranes of
      an optimal angle and length can substantially lower the subglottal pressure at
      which phonation is supported, thus increasing vocal efficiency, and that this
      effect is most pronounced at high frequencies. The implications of this finding
      are discussed for animals such as bats and primates which are able to produce
      loud, high-pitched calls. Modeling efforts such as this provide guidance for
      future empirical investigations of vocal membrane structure and function, can
      provide insight into the mechanisms of animal communication, and could
      potentially lead to better understanding of human clinical disorders such as
      sulcus vocalis.

PMID- 10089620
TI  - Detection of modulation in spectral envelopes and linear-rippled noises by
      budgerigars (Melopsittacus undulatus).
AB  - Budgerigars were trained to discriminate complex sounds with two different types
      of spectral profiles from flat-spectrum, wideband noise. In one case, complex
      sounds with a sinusoidal ripple in (log) amplitude across (log) frequency
      bandwidth were generated by combining 201 logarithmically spaced tones covering
      the frequency region from 500 Hz to 10 kHz. A second type of rippled stimulus was
      generated by delaying broadband noise and adding it to the original noise in an
      iterative fashion. In each case, thresholds for modulation depth (i.e., peak-to
      valley in dB) were measured at several different ripple frequencies (i.e.,
      cycles/octave for logarithmic profiles) or different repetition pitches (i.e.,
      delay for ripple noises). Budgerigars were similar to humans in detecting ripple
      at low spatial frequencies, but were considerably more sensitive than humans in
      detecting ripples in log ripple spectra at high spatial frequencies. Budgerigars
      were also similar to humans in detecting linear ripple in broadband noise over a
      wide range of repetition pitches. Taken together, these data show that the avian
      auditory system is at least as good, if not better, than the human auditory
      system at detecting spectral ripples in noise despite gross anatomical
      differences in both the peripheral and central auditory nervous systems.

PMID- 10089621
TI  - Predicting the detectability of tones with unexpected durations.

PMID- 10089622
TI  - Comments on "broadband spectra of seismic survey air-gun emissions, with
      reference to dolphin auditory thresholds" [J. Acoust. Soc. Am. 103, 2177-2184
      (1998)].

PMID- 10089624
TI  - Comments on "Elephant hearing" [J. Acoust. Soc. Am. 104, 1122-1123 (1998)].

PMID- 10089625
TI  - [The multifocality problem in elective partial nephrectomy for renal-cell
      carcinoma].

PMID- 10089626
TI  - [Radical prostatectomy. The surgical complications].
AB  - Study of 165 patients with prostate adenocarcinoma who underwent radical
      prostatectomy using a retropubic approach. Mean PSA is 19 ng/ml, mean age 63
      years and median follow-up 26 months. 22 patients (13.2%) reported complications
      during the first month post-surgery, primarily urinary fistula of more than 5
      days long in 5 patients and rectal injury in 3.49 patients (29%) reported
      complications after the first month, mainly urinary incontinence in 26 cases and
      stenosis of the urethrovesical juncture in 15. The group with early complications
      showed no significant differences compared to those who had none, neither in PSA
      (p = 0.3) or a worse pathological stage (p = 0.1), and no evidence is shown in
      terms of biochemical progression or in disease free progression (p = 1). Patients
      with urethrovesical juncture stenosis have higher mean PSA (p = 0.01), greater
      biochemical progression (p = 0.006), worse Gleason (p = 0.03 = and worse
      progression free survival (p = 0.01). Patients with stress incontinence showed no
      differences compared to the other groups relative to the studied factors.

PMID- 10089627
TI  - [A reliability analysis of transrectal echographic estimation of prostatic
      volume].
AB  - OBJECTIVE: To establish the reliability of transrectal ultrasound to estimate
      prostatic volume. MATERIAL AND METHODS: Study of 27 patients diagnosed with
      prostate cancer who were managed with radical prostatectomy. Transrectal
      ultrasound assessment of prostatic volume was performed using the revolution
      ellipsoid equation V = (pi/6) x L x T x AP. The values obtained were compared to
      those from radical prostatectomy specimens calculated by the same method and with
      the weights of the specimens. RESULTS: Mean prostatic volume estimated through
      transrectal ultrasound was 38.77 cc vs. 38.46 cc in the pathoanatomical
      specimens. Mean difference between both was 0.31 cc (not significant). The
      coefficient of correlation that related both values was 0.80 and the coefficient
      of correlation between transrectal ultrasound volume and weight was 0.86.
      CONCLUSIONS: Prostatic transrectal ultrasound is an accurate tool to calculate
      total prostatic volume.

PMID- 10089628
TI  - [The Conn syndrome. The clinical and surgical aspects of 18 cases of adrenal
      adenoma].
AB  - OBJECTIVES: Presentation of a series of 18 patients who underwent surgery of
      aldosterone-producing adrenal adenoma (Conn's syndrome) over the last 10 years.
      Assessment of the most significant clinical and pathological aspects from a
      surgical point of view. METHODS: Retrospective study evaluating a broad range of
      features: clinical, analytical, hormonal, imaging, types of anaesthesia,
      approaches, technique used, intra and post-operative morbidity and mortality,
      evolution and pathoanatomical diagnosis. RESULTS: The most frequent clinical data
      of primary hyperaldosteronism were: 94.4% volume-dependent HBP, 50% headaches and
      dizziness, 27.8% epistasis and/or episodes of angor or acute myocardial
      infarction, and 22.2% heart failure. The biochemical study and hormonal testing
      evidenced: hypokalemia in 88.9%, metabolic alkalosis 66.7% and hypernatremia in
      61.1%. Mean aldosterone levels were 517.5 pg/mL, and urinary levels 85.9 mcg/day.
      Resting plasma renin activity (PRA) < 0.2 ng/mL/h in 77.8% cases and positive
      aldosterone stimulation test in 61.1%: captopril test positive. Imaging diagnosis
      was based in CAT which was conclusive in 88.9% and ultrasound which was
      diagnostic in 27.8% cases. The surgical approach was: lumbotomy (over the 11th or
      12th rib) in 14 patients and transpleurodiaphragmatic in all remaining patients.
      The intraoperative complications reported were placement of endothoracic tube due
      to iatrogenic pneumothorax in two occasions. Duration of the procedure (mean
      136.1 min) and post-operative hospitalization (mean 7.76 days), as well as post
      surgery follow-up for up to 96 months were also studied. At final time point
      there was 66.7 asymptomatic patients, 33.3% cases of HBP, and no deaths.
      CONCLUSIONS: Primary hyperaldosteronism due to adrenal adenoma is an uncommon
      reason for HBP, but in most cases can be cured with surgery. Biochemical and
      hormonal testing is determinant to research a diagnosis. Ultrasound and CAT are
      essential for imaging diagnosis, and occasionally NMR can be of help. Lumbotomy
      is considered the choice approach for these small tumours as it is a familial
      technique for urologists with a low complications rate.

PMID- 10089629
TI  - [The management of urinary candidiasis in cystectomized patients].
AB  - Presentation of eight cases of urinary candidiasis in patients who underwent
      radical cystectomy and were managed using by-pass of the urinary tract, oral
      antifungal therapy and solutions in the way of intermittent instillation through
      nephrostomy catheters.

PMID- 10089630
TI  - [The treatment of ureteral lithiasis with a pulsed dye laser].
AB  - PURPOSE: Pulsed dye laser lithotripsy has shown to be an effective and safe
      procedure for treatment of ureteral calculi. We report our experience. MATERIAL
      AND METHODS: A total of 1000 patients were treated with pulsed dye laser between
      January 1990 and February 1996. In 450 patients the procedure was performed under
      general or regional anaesthesia; the remaining 550 patients were treated with the
      aid of a mild sedation. RESULTS: In the mild sedation group a total of 417 out of
      550 patients (75.8%) had their calculi completely cleared (85.6% of effectiveness
      in women with pelvic lithiasis). Different facts caused the treatment to fail in
      the remaining patients: severe pain, vagal reaction and technical difficulties.
      In the anesthesia group the procedure was effective in 346 cases (76.9%). Laser
      failed to clear calculi in 104 patients in this group due to technical
      impossibility and persistence of ureteral fragments. Additional treatment options
      in order to achieve resolution of the calculi were: ESWL, both ESWL and laser,
      Dormia basket, Zeiss stent, three-prong grasping forceps, ureterolithotomy and
      nephrectomy. Morbidity was higher in the group treated under anesthesia, being
      haematuria the most frequent adverse effect. CONCLUSIONS: We believe that
      ureteroscopy and laser lithotripsy is an effective, safe and low morbidity
      procedure for the treatment of ureteral calculi in women with distal calculi. It
      is often suitable to perform it with mild sedation with the subsequent benefit
      for both the patient and health care system regarding to cost-effectiveness
      balance.

PMID- 10089631
TI  - [Treatment by a modified plication of the tunica albuginea in patients with
      congenital penile curvature].
AB  - OBJECTIVE: To evaluate the results obtained with management by modified plication
      of the tunica albuginea in patients with congenital penile incurvation. MATERIAL
      AND METHODS: Between January 1992 and December 1996, a modified plication
      technique of the tunica albuginea was used to correct congenital and acquired
      penile incurvations; the procedure was performed in 27 cases of patients with
      congenital penile incurvation and 17 patients with de la Peyronie's disease. Mean
      age was 22.8 years (range 15-40 years), single ventral incurvation being the most
      frequent (51.8%) type. A modified technique of tunica albuginea plication was
      used. RESULTS: Complete correction of the incurvation was achieved in all
      patients (100%), with a low rate of complications. CONCLUSIONS: Modified
      plication of the tunica albuginea is a simple and effective surgical technique to
      achieve correction of congenital penile incurvations.

PMID- 10089632
TI  - [Spontaneous retroperitoneal hematoma: our experience].
AB  - We report 15 cases of spontaneous retroperitoneal haematoma. The etiology and the
      diagnostic and therapeutic procedures were evaluated. The haematoma source was
      the adrenal gland in 4 patients and the causes were pheochromocytoma (1), adenoma
      (1), myelolipoma (1) and idiopathic (1). In 10 patients the source was the kidney
      and the causes were angiomyolipoma rupture (6), renal cell carcinoma (3) and
      ureteral calculi (1). In the remaining case, the haematoma was produced by
      fibrinolytic and anticoagulant therapy in a patient with acute myocardial
      infarction. The imaging diagnostic techniques employed were abdominal
      ultrasonography and CT scan, which allowed the diagnosis of haematoma and showed
      his size and extension in all the cases. With these two techniques, and with the
      retrograde pyelography in one patient, we obtained the etiologic diagnosis in 12
      of the 15 cases. Surgical treatment was performed in 12 patients (adrenalectomy
      in 2, simple nephrectomy in 3, radical nephrectomy in 5 and partial nephrectomy
      in 2).

PMID- 10089633
TI  - [Endoscopic anterior commissurotomy (EAC) versus TUR as the treatment for the
      neck obstruction syndrome. Our experience. The results].
AB  - OBJECTIVE: 30 patients were included over a 5-year period in a protocol divided
      into two uniform cohorts (age, surgical risk, prostatic volume, etc.). Both
      groups are compared based on morphological effectiveness, functionality, quality
      of life parameters, etc. Also a comparison on the efficacy of anterior
      commissurotomy vs. conventional TUR is carried out. METHOD: After 12 hours, a
      cohort of 15 patients had a Collins' loop section of the vesical neck anterior
      aspect, a technique described by Keitzer (1969). RESULTS: Results were optimal
      and superior to those obtained with TUR. We conclude this technique is effective,
      and emphasize the validity of the concepts described by Gil Vernet in 1956.

PMID- 10089634
TI  - [The use of desmopressin as an alternative in the treatment of nycturia in
      patients with benign prostatic hyperplasia (BPH)].
AB  - OBJECTIVE: Evaluating in patients with benign prostatic hyperplasia (BPH), the
      effects of a synthetic analog of vasopressin (Desmopressin) in the nycturia.
      METHODS: 20 patients with BPH, with a mean age of 68 years that they referred
      marked nycturia of 4 to 10 voiding episodes in the night, they were subject
      treatment with Desmopressin 20 mcg given intranasally before bedtime. RESULTS:
      The nycturia diminishes in the patient, the volume of evacuated urine diminishes
      but in the night that in the day. They were not observed side effects.
      CONCLUSIONS: The desmopressin is an alternative but in the aid to the patient
      with BPH that they presented a marked nycturia.

PMID- 10089635
TI  - [Bilharziasis and bladder cancer. A case report].
AB  - In our setting, the association between bilharziasis and bladder cancer is
      uncommon. However, the presence of recurrent haematuria in a patient from an
      endemic area of bilharziasis (east of Africa and Middle East), is highly
      suspicious of this disease. Lack of an adequate treatment by using anthelminthic
      drugs during the acute phase of disease, might lead to the onset of chronic
      bladder lesions and, on occasion, bladder cancer, of the epidermoid type in the
      majority of cases. Because of the high mortality and aggressivity of this type of
      cancer, an early diagnosis and appropriate treatment of acute lesions is
      mandatory. We report a 40-year-old black male from Senegal, presenting chronic
      bladder schistosomiasis and infiltrative epidermoid carcinoma of the bladder,
      diagnosed and treated in our department by palliative cystectomy.

PMID- 10089636
TI  - [Priapism secondary to a bilateral abscess of the corpora cavernosa].
AB  - Presentation of an exceptional case of priapism in an 82-year-old male, secondary
      to primary bilateral abscess corpus cavernosum. Diagnosis was reached through
      aspiration puncture and pus drainage, which also allowed the resolution of the
      condition. After a literature review, no similar case was found. This was a
      painful, long-lasting erection that resulted from corpus cavernosum repletion
      with purulent material instead of blood.

PMID- 10089637
TI  - [A fibrous pseudotumor of the tunica vaginalis testis. A report of a new case and
      a review of the literature].
AB  - Presentation of one case of benign fibrous pseudotumor of the tunica vaginalis
      testis in a 22-year-old male patient who underwent radical orchiectomy due to
      suspected testicular neoformation. Contribution of radiological findings with
      ultrasound and CAT, emphasizing the significance of considering this rare entity
      as part of the differential diagnosis of extratesticular intrascrotal masses.

PMID- 10089638
TI  - [An adrenal pseudocyst. A report of a new case].
AB  - We report the case of a female young woman with an incidental cystic lesion in
      the left adrenal gland while during a routine study by her gynecologist. The
      change of the aspect in the content of the lesion, its limit size and a not
      definitive study of punction went to the surgical act. This was made with
      preservation of both, adrenal and renal units. The pathological report was
      adrenal pseudocyst.

PMID- 10089639
TI  - [Wunderlich's syndrome in a patient on hemodialysis with acquired cystic kidney
      disease. A report of a new case].
AB  - We report a new case of Wunderlich's syndrome (spontaneous perirenal hematoma) in
      a patient with chronic renal failure undergoing hemodialysis secondary to
      acquired renal cystic disease. The literature relative to this condition is
      review.

PMID- 10089640
TI  - [A massive hernia of the bladder into the scrotum. A report of a case].
AB  - The hernia of the bladder in the scrotum is a highly uncommon observation. From
      the clinical standpoint the usual manifestation is a two-stroke voiding. The
      recommended urological examinations to reach a diagnosis are ultrasound,
      endovenous urography, retrograde urethrocystography and cystoscopy. Management
      includes the de-obstruction of the lower urinary tract, if present, resection of
      associated peritoneum, resection or reduction of the vesical hernia and
      repairment of inguinal path. The case contributed corresponds to a vesical hernia
      in a 72-year-old patient, with no obstructive cause, that was treated surgically
      by resection of the herniated bladder, with good morphological and functional
      results.

PMID- 10089641
TI  - [Transitional-cell carcinoma and renal-cell adenocarcinoma: an unusual case of
      their association in the same kidney].

PMID- 10089642
TI  - [Infection and diabetes].

PMID- 10089643
TI  - [Infectious pathology in diabetic patients cared for in an emergency department].
AB  - OBJECTIVE: We study the influence of diabetes in the incidence of infectious
      diseases attended in an emergency department (ED). PATIENTS AND METHODS: 2,500
      adult patients attended in the ED of a general hospital were examined. We value
      prospectively: clinical data, diagnosis in ED and rate of admissions, comparing
      two groups: Group A (175 diabetic patients), Group B (350 non diabetic control
      patients, with the same age and sex). We used the glycated Hb and the glucose
      levels to make a difference in A Group: patients with good control (A1 = Hb A1c <
      8), patients with poor control (A2 = HbA1c > 8), patients with low glucose levels
      (A3 = glucose < 200 mg/dl) and high glucose levels (A4 = glucose > 200 mg/dl).
      RESULTS: Infectious disease are more frequent in diabetic patients than no
      diabetic (Group A = 13.1% vs Group B = 3.2%), certain amount pneumonia and
      urinary tract infection. Also the infectious diseases are more frequent in
      diabetic patients with high glucose levels (Group A4) than diabetic patients with
      low glucose levels (Group A3), but there were no significant differences between
      A1 and A2 groups. CONCLUSIONS: The presence of diabetes was bound up with a
      higher frequency of infectious diseases, above all pneumonia and urinary tract
      infection, in an ED. The importance of metabolic control in relation with
      infectious diseases is not definite in our study.

PMID- 10089644
TI  - [The effect of human immunodeficiency virus infection on the consumption of
      hospital resources. A correlation with the degree of immunodeficiency].
AB  - BACKGROUND: To calculate the real cost of the Human Immunodeficiency Virus (HIV)
      infection in the use of hospital resources. PATIENTS AND METHODS: All the
      episodes of hospitalization of the years 1993, 1994 and 1995 of a general
      hospital have been analyzed. The patients have been classified according to the
      Patients Management Categories version 5.0 system. The patients with HIV
      infection were also classified according to the CD4+T-lymphocyte counts and the
      existence of AIDS. The derived cost of the stay and the consumption of diagnostic
      and complementary tests were calculated according to PMC Relative Intensity
      Score. RESULTS: In 293 hospitalizations the hospital cost of the HIV patients
      ascended to 145,372,650 ptas, what represents 40,230,000 ptas 100,000 person
      years. HIV patients presented mean of stay (12 vs 5 days, p < 0.001) and hospital
      cost (433,029 vs 218,646 ptas, p < 0.001), significantly higher than non-HIV
      patients. 79% of hospitalizations corresponded to patient with AIDS. As much the
      stay as the hospital cost vary significantly in function of the degree of
      immunologic deterioration (lymphocyte count and AIDS diagnostic). During the
      years of study a stabilization was observed in the cost and the hospital stay of
      these patients. CONCLUSIONS: HIV infection originates a high consumption of
      hospital resources, mainly in patient with advanced immunodeficiency. The
      hospital stay is very high to the general population. In the last years it seems
      to exist a tendency toward the stabilization in the use of hospital resources,
      possibly to expense of the non hospital cost.

PMID- 10089645
TI  - [Human immunodeficiency virus (HIV) infection. The effectiveness of different
      diagnostic sequences in suspected pulmonary infection].
AB  - BACKGROUND: Assessment of different diagnostic sequences, in patients VIH(+) with
      a suspected pulmonary infection. METHODS: A cross-sectional descriptive study of
      76 HIV(+) patients with suspected respiratory infection. It has been determined
      the validity and the pretest and post-test probability of the radiology (Rx) of
      thorax, 67Ga pulmonary scintigraphy and seric LDH levels, in order to design four
      different diagnostic algorithms. RESULTS: The diagnostic sequence Rx-LDH
      scintigraphy with normal results involved an infection probability of 58.0%.
      Pathological Rx with successively normal LDH and scintigraphy, implied a
      likelihood of 97.0%. The LDH elevation in sequence with scintigraphy and Rx rose
      to 96.1% if both were abnormal and diminished to 8.3% if normal. CONCLUSIONS: The
      LDH elevation associated with the sequence of normal Rx and scintigraphy suggests
      a low infection likelihood. On the contrary, associated with pathological Rx and
      scintigraphy in sequence, practically assures the pulmonary infection.

PMID- 10089646
TI  - [A pulmonary cellular immunity study in HIV patients].
AB  - BACKGROUND: Cellular immunity disorder, showed by a decreased blood level of
      lymphocytes T CD4, is the main indicator of progression in HIV infection. The
      diminished level of these lymphocytes and CD4/CD8 ratio in pulmonary samples
      obtained by bronchoalveolar lavage (BAL) is known, so as the enhanced level of
      lymphocytes T CD8, while the pulmonary diseases high incidence in these patients
      could be due to a local immunity disorder or systemic one remains unknown. The
      aim of this study is to compare systemic immunity disorders, studied in blood
      samples, with local immunity replay, showed by BAL samples, in patients with HIV
      infection. METHODS: 74 HIV patients were studied, all of them hospitalized due to
      acute respiratory disease, and undergone to fiberoptic bronchoscopy for
      diagnosing. Cellular and lymphocytic populations are compared and measured by
      flow cytometry in blood and BAL samples. RESULTS: Percentage of total lymphocytes
      and CD4+ population were decreased in BAL samples, above all in patients with CD4
      level minor than 25%. CONCLUSIONS: Cellular immunity disorder of patients with
      HIV infection is bigger in lung than in blood. It's possible to foresee the
      lymphocytes T CD4+ pulmonary depletion from their blood levels.

PMID- 10089647
TI  - [Drug prescription in internal medicine: an analysis of the influencing factors].
AB  - BACKGROUND: The amount and quality of drugs prescribed after hospitalization in
      Internal Medicine and the factors which influence them have been rarely evaluated
      in Spain. MATERIAL AND METHODS: We study prospectively drugs prescribed in
      patients hospitalized in Internal Medicine analyzing amount of drugs before
      admission (BAD), on discharge (DD), end drugs after temporal drugs were removed
      (ED), drugs prescribed as chronic treatment (CTD), symptomatic drugs (SD), acute
      use drugs (AUD) and low therapeutic utility drugs (LTUD). We also evaluated the
      sort of drugs and the factors implicated in increase or decrease of prescription
      volume. RESULTS: Two hundred and eighty-five patients were evaluated [164 males,
      121 females, mean age 68.08 (SD 15.27)]. They had mean BAD 3.42(SD 2.67)7 DD 3.92
      (SD 2.36) (p < 0.001) and ED 3.65 (SD 2.30) (No differences with BAD). The amount
      of drugs were higher in patients 65 years old and elder (p < 0.001). LTUD were
      decreased from 62(22%) patients on admission to 21 (7%) on discharge (p < 0.001).
      Compounded drugs were reduced from 36 (13%) patients to 17 (6%) (p < 0.05). Age
      older 65, length of stay greater 7 days, need for intravenous administration of
      drugs, comorbidities and complications during hospitalization all caused increase
      in prescription volume on discharge. Logistic-regression analysis showed that CTD
      and AUD were the main causes of increase of drugs while BAD and LTUD were
      protective. Drugs reduced in higher proportion were mucolytics (p < 0.005) drugs
      to treat plant-based hyperplasia benign of prostate (p < 0.05), brain
      vasodilators (p < 0.001) and peripheral vasodilators (p < 0.01). CONCLUSIONS:
      Hospitalization in Internal Medicine results in an increase of prescription
      volume though it is short-term. The higher number of drugs is accumulated in
      elderly. Factors implicated in increasing are length of stay, need for
      intravascular access, complications during inpatient, drugs to treat acute
      diseases and chronic use drugs. Low therapeutic utility drugs are used before
      admission in outpatients.

PMID- 10089648
TI  - [Splenic abscess: a case report and review of the literature].
AB  - A patients with multiple splenic abscesses of fungal origin ist presented. It is
      a unusual pathology that generally, only by postmortem ist diagnosed. The
      etiology, clinical features, diagnostic methods and therapeutic measures are
      discussed, and the necessity of early and accurate diagnostic and treatment. The
      prognosis of the splenic abscess is still associated with a high mortality.

PMID- 10089649
TI  - [Home mechanical ventilation as a treatment of the sequelae of tuberculosis
      surgery].
AB  - Nasal intermittent positive-pressure ventilation (NIPPV) has been showed useful
      for the treatment of chronic respiratory failure in patients with chest wall
      diseases due to sequelae of tuberculosis. We present a report of a patient with a
      thoracoplasty and a cavernostomy in situation of chronic respiratory failure.
      Nasal intermittent positive pressure ventilation improved diurnal hypoxaemia and
      hypercapnia.

PMID- 10089650
TI  - [An evaluation of new prevention programs for tuberculous infection. II. BCG
      vaccination].
AB  - Tuberculosis is an infectious disease produced by Mycobacterium tuberculosis in a
      98-99% of the cases and by Mycobacterium bovis in a 1-2%. Its early diagnosis is
      of a great importance because permits to reduce the transmission of the
      infection. Until now, the diagnostic techniques used to discover the
      dissemination of the disease are indirect. We have the PPD skin test and, among
      them, Mantoux is the most common. Correctly used it has a great diagnostic and
      epidemiological value, because it permits to evaluate those patients who can
      obtain a benefit with the chemoprophylaxis when the skin test is positive. We
      analyse the actual via of chemoprophylaxis, when and how it must be used. We
      study not only the drugs for the prophylaxis, but also the good and bad
      utilisation of the BCG vaccine, that it starts to have its indications in other
      countries.

PMID- 10089651
TI  - [Pharmacoeconomics studies in specialized care: the principles, methods and
      practical applications].

PMID- 10089652
TI  - [Hepatic granulomas, giant-cell arteritis and miliary tuberculosis].

PMID- 10089653
TI  - [Acute pancreatitis due to amphotericin B in an HIV-positive patient].

PMID- 10089654
TI  - [The superior vena cava syndrome as a manifestation of aortic dissection
      following aortic valve replacement].

PMID- 10089655
TI  - [Herpes zoster unleashed by rehabilitative therapy].

PMID- 10089656
TI  - [Severe anemia due to hyperthyroidism].

PMID- 10089657
TI  - [Leukocytoclastic vasculitis: a response to treatment with sulfone].

PMID- 10089658
TI  - [An association of multiple myeloma and megaloblastic anemia].

PMID- 10089659
TI  - [Coombs-negative autoimmune hemolytic anemia associated with a primary hepatic
      lymphoma].

PMID- 10089660
TI  - [An oral ulcer due to cytomegalovirus in a patient with the acquired
      immunodeficiency syndrome].

PMID- 10089661
TI  - [Severe colchicine poisoning].

PMID- 10089662
TI  - [Primary brain tumors with initial mental manifestations].

PMID- 10089663
TI  - [Pathological fracture of the ala of the ilium as the form of presentation of an
      adenocarcinoma of unknown origin].

PMID- 10089664
TI  - [Preoperative evaluation of gastric adenocarcinomas: comparison of CT results
      with surgical and patholgic results].
AB  - PURPOSE: The objective of our study was to reassess the value of CT scan in the
      preoperative evaluation of gastric adenocarcinoma, using surgical and pathologic
      findings as the reference standard. MATERIALS AND METHODS: Forty-five patients
      who had preoperative CT scan for gastric carcinoma were retrospectively included
      in the study. Images were analyzed by two readers working in consensus with
      respect to tumor detection, tumor location, depth of invasion, involvement of
      adjacent organs, lymph node involvement and presence of peritoneal
      carcinomatosis. RESULTS: Gastric tumor was visible in 91% of cases. Accurate
      tumor localization was obtained in 50% of cases. Depth of tumor penetration was
      correctly evaluated in 40% of the cases. Evaluation of regional and distant lymph
      node metastases was correct in 54% and 64% of cases, respectively. Peritoneal
      carcinomatosis was depicted in 17% of cases. CONCLUSION: CT scan allows detection
      of gastric adenocarcinoma in the majority of cases. However, this technique
      markedly underscores the extent of gastric adenocarcinoma. Therefore, CT scan
      should not be used to determine the preoperative staging of gastric
      adenocarcinoma.

PMID- 10089665
TI  - [Value of a single low-pressure drain in the postoperative care of bilateral
      thyroidectomies. Retrospective comparison with bilateral Redon drains].
AB  - Double "high vacuum drains" are usually recommended following bilateral
      thyroidectomy. A single "low vacuum drain" is an attractive alternative when the
      surgeon considers drainage is necessary. This retrospective study was designed to
      compare the postoperative outcome following the use of two types of drains. The
      clinical features, biochemical profile and histopathology were comparable between
      the two groups: group 1 (high vacuum, n = 77), and group 2 (low vacuum, n = 71).
      The percentage of total thyroidectomies was significantly higher in group 2 (51%
      versus 34%, p = 0.04) and this discrepancy was adjusted in the statistical
      analysis. There was no statistical difference in the outcome of group 1 versus
      group 2 in terms of wound infections (0% vs 0%), haematoma (0% versus 0.04%),
      duration and volume of drainage (2.1 versus 2.0 days, 118 versus 117 ml), and
      hospital stay (3.2 versus 3.2 days). A single "low vacuum drain" is therefore a
      safe and simple alternative to provide adequate post operative drainage following
      bilateral thyroidectomy.

PMID- 10089666
TI  - [Total hip arthroplasty. Risk factors and prevention of iatrogenic vascular
      complications].
AB  - Vascular injuries during orthopaedic hip surgery are rare. However, they must
      always be feared because they threaten life and limb. We present 11 vascular
      injuries observed over a 12-year period. Seven women and 4 men, treated by
      elective surgery, presented 14 vascular injuries (6 arterial, 5 venous and 3
      prosthetic vascular graft). Four injuries occurred during revision procedures.
      They were all operated as an emergency for ischaemic syndrome (6 cases) and/or
      haemorrhage (7 cases). Four patients (37%) died and 4 developed sequelae, various
      directly attributable to the vascular injury. In the light of these cases, we
      tried to determine the various mechanisms of the injury and the orthopedic and
      vascular risk factors. Preoperative detection and well defined therapeutic rules
      are very important for the prevention of these severe vascular accidents.

PMID- 10089667
TI  - [Nissen fundoplication done by remotely controlled robotic technique].
AB  - Two Nissen fundoplications were performed by a minimally invasive robotic
      technique on May 19, 1998. The Mona robot, was placed to the left of the patient.
      It held and activated surgical tools. The surgeon was placed some 3 meters from
      the patient and was seated at a console. He was not scrubbed. He commanded the 3
      robotic arms by manipulating two handles, while observing a 3 dimensional picture
      recreated by a binocular system. Manipulations of the handles were translated
      into digital information by a computer. This information was modified by the
      computer with downscaling of the amplitude of motion by a factor 1 to 3 or 1 to
      5. Physiologic tremor was eliminated. The computer delivered an impulse in
      command of the articulated robot arms via a 5 m long cable. Operating time was
      4.30 hours, and 1.30 hours respectively. Blood loss was estimated at 20 and 30
      ml. The two patients were discharged on the first postoperative day after a
      gastrograffin swallow had been performed in order to check the position of the
      wrap and its patency. Our experience with the Mona device may suggest that
      surgical robotics could have an increasingly important role in tomorrow's
      operating theatres. It should allow for more precise procedures, performed under
      better circumstances.

PMID- 10089668
TI  - [Gastric mucosa-associated lymphoid tissue lymphomas (MALT) and their treatment].

PMID- 10089669
TI  - [Anesthesia and postoperative recovery for parathyroid gland surgery].
AB  - Anesthesia for surgery of primary hyperparathyroidism (HPT) usually concerns
      asymptomatic elderly women with moderate hypercalcemia. Cardiovascular
      repercussions of the endocrine disorder are possible, but they are not frequent
      except for hypertension. Hyperparathyroid crisis is a life-threatening condition
      with severe hypercalcemia. Intravenous diphosphonates are very effective drugs to
      control hypercalcemia. The improvement is transient but allows curative
      parathyroidectomy to be performed with a minimal risk of cardiac arrhythmias.
      Anesthesia for surgery of secondary HPT concerns patients with chronic renal
      failure treated by hemodialysis. Cardiovascular disease is frequent and
      aggravated by the endocrine disorder. In patients with marked aortic stenosis or
      severe left ventricular dysfunction, parathyroidectomy should be performed by
      cervicotomy under local anesthesia. Hyperparathyroidism may persist after renal
      transplantation (tertiary HPT): in this case cardiovascular disease is minimal
      and the hypercalcemia is moderate. Parathyroidectomy is usually performed by
      cervicotomy under general anesthesia. Sternotomy is required in the case of an
      abnormal mediastinal location of a gland. An interaction between myorelaxants and
      hyperparathyroidism has been observed. Total blood calcium must be systematically
      assayed postoperatively because postoperative hypocalcemia is constant.
      Hypocalcemia is moderate in primary and tertiary HPT, due to transient functional
      hypoparathyroidism, with lowest observed the 2nd or 3rd postoperative day.
      Hypocalcemia should not be treated when asymptomatic because it resolutes on the
      4th or 5th postoperative day. Intravenous calcium infusion may be necessary for 1
      or 2 days, if serum calcium is below 1.9 mmol per liter with symptoms of tetany.
      Persistent hypocalcemia is due to an hungry bone syndrome or organic
      hypoparathyroidism that should be treated by oral vitamin D and calcium. In
      secondary HPT, hypocalcemia is early, marked and asymptomatic. Treatment must
      often be started on the 6th postoperative hour by intravenous calcium infusion,
      followed by oral vitamin D and calcium. The absence of postoperative hypocalcemia
      indicate incomplete removal of all abnormal parathyroid tissue. At the third
      postoperative day, a second cervicotomy may be performed to complete the neck
      exploration.

PMID- 10089670
TI  - [Partial wound closure in one layer with running sutures: how to tie off the
      suture without injuring the viscera or a finger?].

PMID- 10089671
TI  - [Cystic dystrophy of the duodenal wall in aberrant pancreas].
AB  - Cystic dystrophy of the duodenal wall developing in heterotopic pancreas is rare.
      Pancreaticoduodenectomy is usually advocated in cases of symptomatic cystic
      dystrophy without chronic pancreatitis but little is known about long-term
      results. We report a case of cystic dystrophy of the duodenum wall developing in
      heterotopic pancreas responsible for abdominal pain and duodenal obstruction
      associated with chronic pancreatitis. Pancreaticoduodenectomy allowed complete
      relief of symptoms. Chronic pancreatitis associated with cystic dystrophy may
      complicate the choice of appropriate therapy.

PMID- 10089672
TI  - [Obstructive icterus due to a solitary portal hepatic tuberculous
      lymphadenopathy].

PMID- 10089673
TI  - [False aneurysm of the brachiocephalic arterial trunk. Report of an operated
      cases].

PMID- 10089674
TI  - [Spontaneous rupture of the spleen during acute pancreatitis. A case report].

PMID- 10089675
TI  - [Mesenteric extragonadal metastasis of a nonseminomatous germinal tumor].

PMID- 10089676
TI  - [Recommendations of the British health minister for the treatment of colorectal
      cancers].

PMID- 10089677
TI  - Bone giant cell tumour in neuropathological practice. A fifty year overview.
AB  - We report a case of a 29-year-old female patient who suffered from visual
      disturbance, resulting from a lesion in the sphenoid bone which, histologically,
      proved to be a giant cell tumour. Reviewing our laboratory practice over a 50
      year period, only 7 cases of true giant cell tumour were found and they were in
      two major locations, i.e. the skull and vertebrae. These few cases led us to
      focus on the problem raised by the lack of histological patterns of malignancy.
      In agreement with Mazabraud's theory, it seems that a vertebral location is
      associated with a good prognosis and that gene mapping of chromosome 17 in
      relation to p53 mutations could be a valuable tool in the diagnosis of potential
      malignant behaviour.

PMID- 10089678
TI  - [Central neurocytoma. Immunohistochemical study: MIB1, p53 and bcl-2. Report of 5
      cases].
AB  - To further characterize central neurocytoma, a rare intraventricular tumour
      described in 1982, we analyzed six tumours by immunohistochemistry for MIB1, p53
      and bcl-2. bcl-2, an inhibitor of p53-mediated apoptosis is frequently expressed
      in gliomas, especially in tumors with wild-type p53. Its expression in peripheral
      neuroblastomas suggests a down-regulation during final terminal differentiation.
      Six tumors from five patients (one female/four males, age ranged from 18 to 63
      years) were examined. All patients were alive from 2 to 88 months after initial
      surgical resection. On histological sections, tumours demonstrated a typical
      pattern. Synaptophysin staining was seen in all cases. Proliferation index was
      low (< 4.5%). bcl-2 was never expressed. p53 expression varied but within low
      values (< 10% of cells). These latter antibodies were rarely analyzed until now
      in this usually benign neoplasm which represents a well differentiated variant of
      neuron derived tumors.

PMID- 10089679
TI  - [Papillary fibroelastoma of the heart. A review of 20 cases].
AB  - After a period during which cardiac papillary fibroelastomas were considered
      incidental autopsy findings cerebral and coronary arteries embolism proved their
      aggressiveness. Echocardiography is now able to identify them and surgical
      resection is rapidly required. Sea anemone like macroscopic pattern is
      characteristic with finely villous masses, each frond being at microscopical
      examination formed by a central fibroelastic core surrounded by a myxomatous
      layer overlied by endothelial cells. Histogenesis remains elusive and we tried to
      clarify it by immunohistochemical analysis of 8 of the 20 cases studied (10
      autopsies, 10 surgical resections). Morphological and immunohistochemical data
      show that endothelial cells play the most important part in abnormal formations.

PMID- 10089680
TI  - [Granular cell tumor. Epidemiology of 263 cases].
AB  - 263 cases of granular cell tumour had collected [thanks to the collaboration of
      pathologists Septentrional Association of North, Pas-de-Calais and Aisne
      departments (A.S.A.P.)]. We studied the age, sex, localisations and the
      particularity of these tumours. These results had compared to other large series
      of the literature. Our study showed a majority of men (68%), twenty to sixty year
      old. The preferential sites are skin (38.57%), oesophagus (19.64%) and tongue
      (10%). The granular cell tumour is multiple in fifteen cases and associated to
      neoplastic tumour in twelve cases. Only one case recurred after incomplete
      excision. There were none malignant tumour.

PMID- 10089681
TI  - [Granular cell tumor and congenital epulis. Histochemical and immunohistochemical
      of 58 cases].
AB  - 56 cases of granular cell tumour and 2 cases of granular cell congenital epulis
      have been studied morphologically, histochemically and immunohistochemically. The
      subject of this study is to evaluate the diagnosis interest of the PAS stain,
      determine the positivity of 4 antibodies (vimentin, NSE, PS100, NK1/C3) and
      confirm or not the neuroectodermic origin. The study showed that the microscopic
      findings are often sufficient. When the diagnosis is less evident, the PAS stain
      is not discriminant, but we can use the immunohistochemistry study: we confirmed
      the positivity of the 4 antibodies, but PS100 and NK1/C3 are the most constant.
      Only the 2 cases of granular cell congenital epulis always show negative
      immunoreactivity with S100 protein. About the histogenesis, our study confirm the
      neurogenic origin, but the hypothesis of a non neoplastic nature is raised.

PMID- 10089682
TI  - [Primary gastric MALT lymphoma in children. Report of 2 cases].
AB  - Primary gastric MALT non-Hodgkin's lymphoma is rare in immunocompetent children.
      To our knowledge, only two cases have been previously described. We report two
      cases of gastric MALT lymphoma associated with Helicobacter pylori. Clinico
      pathological features are similar to those observed in adults. The relationship
      between the microbial infection and non-Hodgkin's lymphoma development is
      discussed.

PMID- 10089683
TI  - [Biotin-rich pseudoherpetic intranuclear inclusions. A diagnostic pitfall].
AB  - Biotin-rich pseudoherpetic nuclear inclusions may be observed in endometrial
      epithelial cells during pregnancy, post-partum or in association with
      choriocarcinoma. They may be observed in tumor cells in a few papillary
      carcinomas of the thyroid gland in young women. These inclusions may be
      responsible for false diagnoses of herpesvirus infection at morphological and
      immunocytochemical examination. They may be responsible for false positives in
      immunocytochemistry and in situ hybridization.

PMID- 10089684
TI  - [Extramembranous glomerulonephritis: clinicopathologic finding in a group of 45
      Cameroonians].
AB  - Forty five Cameroonian patients in West Africa who were diagnosed as having
      membranous glomerulonephritis (MGN) were studied and followed up over a five year
      period. The mean age of these patients was 32.3 years with a female to male ratio
      of 5/4. Proteinuria (93.3%) and nephrotic syndrome (89%) were the two most
      important clinical manifestations at the time of diagnosis. Seventeen cases
      (37.8%) of the MGN were considered idiopathic while 62.2% were associated with
      known aetiological factors. Histologically, the majority of patients were at
      stage I (35.55%) or stage II (37.8%) of the World Health Organisation (WHO)
      classification. Except of the patients in stage I, most patients in stage II and
      all those in stages III and IV, showed associated important, tubular interstitial
      and vascular lesions. Immunofluorescence studies showed deposits to be mainly IgG
      (80%) and C3 (71.1%) while electron microscopy showed varied dense deposits in
      all cases. Seventeen patients with idiopathic MGN and 10 MGN patients whose only
      associates aetiological factor was a positive hepatis B antigen were followed up
      over 5 years. During this period, eight patients (29.6%) had a complete clinical
      remission, eleven patients (40.7%) improved their renal function and decreased
      their 24 hour proteinuria, while eight (29.6%) patients deteriorated into end
      stage renal failure and had to be commenced on dialysis; three of them died
      during this procedure.

PMID- 10089685
TI  - [Papillary fibroelastoma: a cardiac tumor rarely reported in children].
AB  - Papillary fibroelastoma is a seldom reported tumour. It usually occurs in adults
      and develops on the aortic and mitral valves. It is not different of giant Lambl
      excrescences and differential diagnostic can be difficult with the myxoma. Its
      systematic surgical ablation is justified by the important risk of embolic
      complications. It has rarely been reported in children. We report a case peculiar
      by fortuitous diagnostic, tricuspid site, large size and occurrence in a 3-year
      old child.

PMID- 10089686
TI  - [Peritoneal pseudomyxoma associated with an ovarian and appendicular mucinous
      tumor].
AB  - The authors report a case of pseudomyxoma peritonei associated with an
      appendicular and ovarian mucinous tumor. They emphasize the rarity of bilateral
      ovarian and appendicular involvement and they discuss the problem of the origin
      of the primary tumor and evaluation of the prognosis.

PMID- 10089687
TI  - New knowledge about acoustic neuromas.

PMID- 10089688
TI  - Keratinized epithelial folds in the external auditory canal.

PMID- 10089689
TI  - Unusual appearance of the maxillary sinus ostium on transnasal endoscopy.

PMID- 10089690
TI  - Recurrent invasive papilloma of the vocal fold.

PMID- 10089691
TI  - Temporal bone hemangioma as a cause of facial paralysis.

PMID- 10089692
TI  - Alternate binaural bithermal response.

PMID- 10089693
TI  - Management of neurofibromatosis type 2.
AB  - Neurofibromatosis type 2 (NF2), an as-yet incurable disease that predisposes
      patients to multiple intracranial and spinal tumors, requires a team approach to
      treatment, because of its multisystem nature. Included on the team should be
      neuro-otologists, neurosurgeons, ophthalmologists, geneticists, audiologists,
      speech therapists and other rehabilitative personnel, including counselors,
      psychologists and, occasionally, psychiatrists. The challenge is to arrive at a
      treatment strategy that preserves useful hearing and quality of life without
      increasing the risk of complications to the facial nerve or compromising
      neurologic status. Choosing the best treatment approach involves considering a
      complex set of competing factors that affect various aspects of the patient's
      outcome.

PMID- 10089694
TI  - Neurofibromatosis type 2: genetic and clinical features.
AB  - For decades, neurofibromatosis type 2 (NF2) was misclassified with the more
      common neurofibromatosis type 1 (NF1), until 1987 when it was found via genetic
      linkage analysis that the gene for NF1 was localized to chromosome 17 and the
      gene for NF2 was localized to chromosome 22. Large, population-based studies have
      shown that vestibular schwannomas (VS), the hallmark of NF2, do not occur at
      increased frequency in patients with NF1. Typical clinical features of NF2 are
      bilateral VS or a family history of NF2, plus either unilateral VS or any two of
      the following: meningioma, glioma, neurofibroma, schwannoma or posterior
      subcapsular lenticular opacities. Presymptomatic genetic tests are now possible
      in the majority of families, and it is hoped that somatic gene therapy will be
      developed for the treatment of this disease.

PMID- 10089695
TI  - Imaging in neurofibromatosis type 2: screening using magnetic resonance imaging.
AB  - NF2 is a distinct entity characterized by bilateral eighth-nerve schwannomas,
      other intracranial schwannomas and meningiomas, and multiple spinal canal
      schwannomas, meningiomas and gliomas. Screening of the entire neural axis is
      mandatory because of the incidence of asymptomatic lesions. MRI is the technique
      of choice, particularly employing contrast-enhanced, T1-weighted sequences in
      multiple image planes.

PMID- 10089696
TI  - Central electrical stimulation of the auditory pathway in neurofibromatosis type
      2.
AB  - The auditory brainstem implant (ABI) is a viable treatment option for patients
      with neurofibromatosis type 2 (NF2) whom either vestibular schwannomas or the
      surgery used to remove them has rendered totally deaf. This device stimulates the
      central auditory pathways in a manner similar to the cochlear implant in
      individuals with a total hearing loss. A multichannel model with transcutaneous
      signal transmission is in use experimentally in both the United States and
      Europe. Of 14 patients implanted with the ABI in a European pilot study, 13
      received auditory sensations at initial tuning. Surgical implantation of the ABI
      is generally, but not always, performed at the same time as tumor removal, with
      the preferred route being the transmastoid-translabyrinthine approach. After
      insertion, monitoring of the device is required to optimize the location of its
      electrode on the cochlear nucleus complex.

PMID- 10089697
TI  - Cranial polyneuropathies in multiple sclerosis: case report and literature
      review.
AB  - Although cranial neuropathies are common disorders in multiple sclerosis
      patients, multiple cranial nerve involvement is an unusual occurrence.
      Correlation of clinical symptoms with magnetic resonance imaging evidence of
      demyelinating central nervous system lesions can confirm the diagnosis. The
      authors report on the case of a 43-year-old woman who initially was thought to
      have suffered a brainstem infarct but, in fact, had developed multiple cranial
      nerve functional deficits. Treatment of multiple sclerosis remains primarily
      supportive in nature, with corticosteroids used for acute exacerbations and
      chronic progression.

PMID- 10089698
TI  - Giant lipoma of the larynx: a case report and literature review.
AB  - Fewer than 15% of lipomas occur in the head and neck. To date, fewer than 100
      cases of laryngeal lipoma have been reported in the literature. Typical clinical
      manifestations include dysphagia, dyspnea and hoarseness, as well as the presence
      of a smooth or pedunculated mass seen endoscopically and a low attenuation mass
      on computed tomography scan. Pathologic sections commonly reveal a tumor
      consisting of mature adipocytes, which is often encapsulated. Treatment of
      laryngeal lipoma varies from conservative total endoscopic removal to external
      surgical approaches. The following is a report of a single case of laryngeal
      lipoma, including pathologic and radiologic findings, as well as a review of the
      literature.

PMID- 10089699
TI  - [The effect of continuous clasps on the state of residual teeth].
AB  - 170 removable partial dentures connected with continuous clasps (Kennedy bar) of
      162 patients have been examined. In the case of 77 dentures the continuous clasps
      were tooth-supported, whereas in the other 93 cases tooth-supports has not been
      used. Authors examined the effect of dentures on the periodontal tissues, by
      measuring the frequency of occurrence of gingivitis, pocket formation, and
      increased tooth movability. Teeth, touching the tooth-supported clasps suffered
      from damage of the periodontal tissues in 20.1%. This value increased to 38.4% in
      the case of clasps without tooth-support.

PMID- 10089700
TI  - [Sinus elevation and its control by 3D computer tomography].
AB  - We have performed 3D CT examinations before and after 21 uni- and bilateral sinus
      elevations, immediately prior to loading of the implants and 1 year after the
      loading. Comparison of the results with those of panoramic and the customary CT
      examinations yielded the following useful information. Any possible difference
      between planning and performance may be controlled. The fate of biomaterial
      implanted in the maxillary sinus was followed. The 3D CT projections providing
      most information were established (from a superior position downwards; from
      lateral and posterior positions forwards). Possible errors can be discovered
      before the implant is loaded. The cases in which it is worthwhile to perform this
      costly examination were determined: surgical complications, documentation,
      extensive alveolar atrophy etc. The results of sinus elevation with different
      bone substitute materials can readily be compared (e.g. autogenous bone + HTR
      Bioplant on one side, and autogenous bone + Algipore on the other side).

PMID- 10089701
TI  - [Bacterial flora of odontogenic and non-odontogenic inflammations of the oro
      facial region].
AB  - Samples were collected from 34 patients after extraoral incision in case of
      infections of oro-facial region (29 odontogen and 5 non odontogen). The authors
      examined the prevalence, ration and susceptibility of the isolated bacteria to
      antibiotics. The 98-100% of the bacteria has found were sensitive to Clindamycin
      and Amoxicillin/Clavulan acid. These antibiotics could be the first choice to
      treat the above mentioned diseases.

PMID- 10089702
TI  - [Function of the central sterilization office at the Semmelweis Clinic of
      Conservative Dentistry and Prosthodontics].
AB  - In order to prevent cross-infection by blood borne and other pathogens central
      sterilization department has been constructed in the common building of the
      Depts. of Conservative Dentistry and Prosthodontics. Instrument sterilization is
      accomplished in six steps: (1) consolidation and transport of instruments, (2)
      cleaning, (3) packaging, (4) sterilization, (5) storage, (6) sterilizer
      monitoring. This process is performed by trained sterilization technicians to
      ensure that attending faculty, student dentists, clinical staff and patients are
      protected from cross-infection caused by contaminated dental instruments.

PMID- 10089703
TI  - [Treatment with omeprazole, clarithromycin and amoxicillin over 6 days in
      patients with Helicobacter pylori-infected duodenal ulcer].
AB  - OBJECTIVE: To investigate the eradication rate of Helicobacter pylori with
      omeprazole, amoxicillin and clarithromycin during 6 days in patients with
      duodenal ulcer. To compare the reliability of the analysis of the eradication
      with urea-13C breath test performed one month and 3 months after therapy. To
      evaluate the one-year reinfection rate. PATIENTS AND METHODS: Prospective study
      including 99 patients with duodenal ulcer (65 with acute disease and 34 in
      maintenance treatment) infected by Helicobacter pylori (urease rapid test and
      urea-13C breath test positive). Patients were treated with omeprazole 20 mg,
      clarithromycin 500 mg and amoxicillin 1 g, b.i.d., during 6 days. The infection
      status was investigated 1 and 3 months after treatment by urea-13C breath test.
      The one-year reinfection rate was investigated using the same test. RESULTS: Per
      protocol eradication rates were 76% (95%-CI: 66-84) one month and 73% (95%-CI: 63
      81) 3 months after treatment. In the intention to treat analysis, eradication
      rates were 74% (95%-CI: 64-82) and 70% (95%-CI: 60-79), respectively. Side
      effects were mild and uncommon. The rate of false negative urea-13C breath test
      results one month after therapy with respect to 3 months was 4.2% (95%-CI: 0.8
      11.7). One-year reinfection rate determined in 56 patient was absent.
      CONCLUSIONS: The eradication of Helicobacter pylori with triple therapy for 6
      days in patients with duodenal ulcer is not satisfactory. To investigate
      Helicobacter pylori infection with urea-13C breath test one month after treatment
      overestimates the results of the eradication. One-year reinfection rate is
      clinically irrelevant.

PMID- 10089704
TI  - [Percutaneous intrahepatic portosystemic shunt: its effects on hypersplenism].
AB  - The aim of this study was to verify the early effects that the transjugular
      intrahepatic portosystemic shunt (TIPS) produces on thrombocytopenia and its
      possible relationship to portal pressure and the size of the spleen. A TIPS was
      placed in 24 cirrhotic patients (11 women and 13 men) with a mean age of 57.6 +/-
      12.3 years. Prior to the test the platelets count, the size of the spleen and the
      portocaval gradient were determined. The same parameters were evaluated one day
      and one month afterwards. A significant increase was observed in then number of
      platelets following the placement of the prosthesis (87.6 +/- 55.2 vs 97 +/- 66.8
      x 10(9)/l) (p < 0.05) which was maintained in the monthly control without
      achieving statistical significance (99.5 +/- 60.8 x 10(9)/l). A significant
      decrease was also observed in the size of the spleen from 156.7 +/- 28.7 mm
      during the previous control to 144.5 +/- 19.9 mm in the monthly control (p <
      0.05). The portocaval gradient was significantly reduced following the procedure
      with the values being 23.25 +/- 3.86 mmHg prior to the TIPS, 10.29 +/- 3.84 mmHg
      in the immediate control and 10.37 +/- 4.81 mmHg at the one month control. A
      statistically significant correlation was observed between the size of the spleen
      and the number of platelets in both the previous control (r = 0.7264; p < 0.001)
      and in the monthly control (r = 0.5764; p < 0.05), between the size of the spleen
      and the portocaval gradient prior to the test (r = 0.5285; p < 0.05) and at one
      month (r = 0.7185; p < 0.01) and between the portocaval gradient and the number
      of platelets before the prosthesis (r = 0.5060; p < 0.05). TIPS may improve the
      thrombocytopenia in correlation with the decrease in portal pressure.

PMID- 10089705
TI  - [Anti-Sp100 and anti-Gp210 in the diagnosis of primary biliary cirrhosis in
      patients with autoimmune cholangitis].
AB  - We describe 2 women with features of autoimmune cholangitis. Serum biochemical
      studies showed cholestasis and increased immunoglobulin M with negative
      antimitochondrial antibodies. Markers of hepatitis B and C viruses were absent.
      Both had positive antinuclear antibodies. One had a speckled pattern (multiple
      nuclear dots) and the other a perinuclear pattern (pore nuclear). In the first
      case anti-Sp100 was positive by EIA and in the second anti-Gp210 was detected by
      immunoblot. Diagnosis of primary biliary cirrhosis was made and the patients were
      treated with UDCA. Current knowledge indicates that determination of anti-Sp100
      and anti-Gp210 substantially improves diagnosis of primary biliary cirrhosis as
      these ANA are highly specific for this disease. These autoantibodies may lead to
      the classification of different groups of patient included in autoimmune
      cholangitis. All patients with autoimmune cholangitis should be tested for anti
      Sp100 and anti-Gp210.

PMID- 10089706
TI  - [Hepatic inflammatory pseudotumor: apropos a case with a response to steroid
      treatment].
AB  - A new case of hepatic inflammatory pseudotumor (HIP) is reported. A 66-year-old
      woman presented with fever and toxic syndrome. Analysis demonstrated an elevation
      in erythrocyte sedimentation, CRP, leukocytosis and normocytic anemia. A lesion
      was observed on ultrasonography in the right hypoechoic hepatic lobe with echos
      within (mosaic pattern). The lesion was hypodense on CT scan and was
      hypervascularized on angiography. NMR was hypointense on T1 and hyperintense on
      T2. The patient underwent surgery with intraoperative biopsy being performed.
      Hepatectomy was not carried out given negativity of malignancy. Following surgery
      the patient remained asymptomatic and the analytical alterations normalized.
      After a asymptomatic 5-year period the clinical-analytical alterations reappeared
      following erysipelas. Fever showed partial response to non steroid
      antiinflammatory drugs and a satisfactory response to corticoids. Studies are
      required to evaluate the role of corticoid treatment in this disease.

PMID- 10089707
TI  - [Severe lower digestive hemorrhage in Crohn's disease].
AB  - Severe or massive lower gastrointestinal bleeding is an unusual complication of
      inflammatory bowel disease that has traditionally associated with ulcerative
      colitis, although it can also appear in 0.6-2% of the cases in Crohn's disease.
      Two cases of severe lower gastrointestinal bleeding in Crohn's disease, one of
      them with ileocolic and another with ileal involvement are presented. Surgical
      treatment is supported by potential severity, high frequency of the relapse and
      data indicate a good prognosis after intestinal resection. It can be performed
      immediately if the persist bleeding or elective, as the 2 cases that we present,
      in the patients that are stabilized.

PMID- 10089708
TI  - [The primary prevention of cholesterol biliary lithiasis: the present and
      future].

PMID- 10089709
TI  - [Ebrotidine-induced acute hepatitis].

PMID- 10089710
TI  - [5-Aminosalicylic acid-induced acute pancreatitis].

PMID- 10089711
TI  - [Local anesthetic infiltration with mepivacaine and bicarbonate prior to
      performing a liver biopsy].

PMID- 10089712
TI  - [Recurrent spontaneous bacterial peritonitis due to encapsulated microorganisms
      (Haemophilus influenzae and Streptococcus pneumoniae) in a patient with liver
      cirrhosis].

PMID- 10089713
TI  - [Spontaneous bacterial peritonitis due to Citrobacter freundii].

PMID- 10089714
TI  - Optimal control of blood pressure can reverse left ventricular hypertrophy in
      uremic hypertensive hemodialysis patients.
AB  - We investigated the effects of antihypertensive treatment on left ventricular
      hypertrophy (LVH) of long-term hemodialysis patients. In uremic patients, it is
      still controversial in antihypertensive effect to the regression of LVH. The left
      ventricular size and function of 39 uremic hypertensive long-term hemodialysis
      patients (27 men, 12 women, mean age 58.3) was evaluated with M-mode, 2
      dimensional and Doppler echocardiography before, and 12 months after, the start
      of combined antihypertensive therapy. This therapy included angiotensin II
      converting enzyme inhibitors, beta-blockers and calcium antagonists. Patients
      were classified as responders or nonresponders, depending upon whether their
      systolic blood pressure (SBP) decreased by more than 10 mmHg after
      antihypertensive treatment for 12 months. Before treatment, 36 (92%) patients had
      LVH and diastolic dysfunction and three (8%) had systolic dysfunction. At the end
      of 12 months, only 25 (64%) patients had LVH, 30 (77%) had diastolic dysfunction
      and 2 (5%) had systolic dysfunction. Left ventricular mass index (LVMI) also
      decreased from 203.63 +/- 70.47 g/m2 to 178.57 +/- 67.31 g/m2. LVMI correlated
      with systolic blood pressure (SBP) but did not correlate with diastolic blood
      pressure (DBP). There were 26 responders and 13 non-responders. Among responders,
      both the SBP (153.91 +/- 13.24 mmHg vs 134.43 +/- 14.21 mmHg, p < 0.01) and DBP
      (90.39 +/- 7.89 mmHg vs 79.98 +/- 7.35 mmHg, p < 0.01) decreased significantly
      after antihypertensive therapy. Responders also exhibited progressive regression
      of LVH (LVMI decreased significantly from 208.52 +/- 72.03 g/m2 to 168.52 +/-
      55.53 g/m2, p < 0.05). However, LVH regression was not found in nonresponders
      (LVMI showed 194.84 +/- 64.36 g/m2 vs 193.66 +/- 77.67 g/m2). We conclude that
      good control of blood pressure can reverse LVH in hypertensive hemodialysis
      patients.

PMID- 10089715
TI  - Intracranial meningioma with hemorrhage.
AB  - Intracranial meningioma with hemorrhage is not frequently reported. The available
      articles in the literature regarding intracranial meningioma with hemorrhage are
      reviewed to the best of our knowledge, and the sixty-one cases have so far been
      reported. The authors report three cases. In about half of the 64 cases including
      ours, the tumor was located at the convexity, and histologically classified as
      meningotheliomatous meningioma. The site of hemorrhage was mainly in the
      subarachnoid space. In most cases the onset of presenting signs and symptoms was
      acute. The mean age at the time of tumor hemorrhage was 51 years. There was no
      sex difference statistically. The importance of the diagnosis of associated
      hemorrhage and subsequent surgical intervention is emphasized.

PMID- 10089716
TI  - Subacute pituitary apoplexy-analysis of 17 cases.
AB  - We retrospectively study 17 cases (total cases 197), receiving surgery at
      Kaohsiung Medical College Hospital, which are proved to be subacute pituitary
      apoplexy via preoperative computerized tomograms, magnetic resonance imagings,
      operative findings and pathological proof. Fourteen patients had headache; 15
      cases were with visual disturbance including visual defect, blindness. One case
      was found incidentally to have a cerebral vascular attack. None of these cases
      received bromocriptine. Preoperative computerized tomograms (CT) aided the
      initial diagnosis and magnetic resonance imaging (MRI) is preferred for
      radiological investigation in displaying the metabolic products of hemorrhage
      within the pituitary tumors. Operative findings revealed xanthochromic fluid with
      liquid-like tumor debris or chocolate-like content. All these patients received
      hormone supplement when pituitary apoplexy was highly suspected.

PMID- 10089717
TI  - Stability of self-prepared fortified antibiotic eyedrops.
AB  - Self-prepared fortified antibiotic eye drops are essential for the severe ocular
      infection. The relation of potency decay and storage conditions including
      temperature, concentration and duration were studied by the changes of MIC. 1%
      and 10% amikin, 10% and 50% pipril, and 5% and 25% vancomycin were diluted from
      the prarenteral antibiotics with the 5% glucose and storage at 4, -18 and -80
      degrees C for 3, 7, 14 and 28 days. MICs of amikin against Pseudomonas
      aeruginosa, pipril and vancomycin against Staphylococcus aureus were determined
      by the agar diffusion method. Fluctuations of the MIC were noted during the
      observation period. Most of the significant changes of MIC were found during the
      first 7 days. When the potencies between time of zero and 28 days are compared,
      only 10% pipril and 25% vancomycin stored at -80 degrees C had significant
      change. Our conclusion is that all of the fortified antibiotic eye drops in this
      study can be stored in the house refrigerator or freezer for up to 28 days. High
      concentration may show a negative result of the preservation. Temperature does
      not influence the preservative effect within four weeks' observation.

PMID- 10089718
TI  - Effect of different anticoagulant, underfilling of blood sample and storage
      stability on selected hemogram.
AB  - We collected blood samples from 94 adult non-hematological outpatients and
      inpatients for complete blood count (CBC) without any flagging at Kaohsiung
      Medical College Hospital in order to investigate the effect of (1) different
      anticoagulants with Na2 EDTA vs K3 EDTA (2) the underfilling of blood collection
      volume (2 ml, 3. 5 ml vs standard 5 ml) (3) the difference in storage stability
      between 1 hour, 4 hours, 8 hours and 12 hours after venesection at room
      temperature on some selected hemogram parameters (WBC, RBC, hemoglobin,
      hematocrit, MCV, MCH, MCHC, platelet, percentage of neutrophil and lymphocyte).
      The automated hematology analyzer we used was SYSMEX NE-8000, (TOA, Japan). All
      the EDTA collection vacutainer tubes were supplied by Becton-Dickinson (New
      Jersey, U. S. A.) with the same lot number. Paired t- test was used for
      statistics. We found that values of hemoglobin, hematocrit, MCV and lymphocyte
      percentage collected in Na2 EDTA tubes were significantly higher than those
      collected in K3 EDTA (P < 0.05 for hemoglobin and lymphocyte percentage, and P
      all < 0.01 for others), while values of MCHC collected in Na2 EDTA were
      significantly lower than those collected in K3 EDTA (P < 0.05). For underfilling
      of blood sample, values of hematocrit and MCV with 2 ml blood volume were
      significantly lower than those with 5 ml blood volume (both P < 0.01), while
      values of MCHC with 2 ml blood volume were significantly higher than those with 5
      ml blood volume (P < 0.01). When the collection blood volume was increased to 3.5
      ml, there were no significant difference between values for 3.5 ml and 5ml blood
      volume (P all > 0.05). In the storage stability study, there was a significant
      sequential increase of hematocrit and MCV between 1 hour, 8 hours and 12 hours (P
      < 0.05 and < 0.01, respectively, for 8 hours, P all < 0.01 for 12 hours). There
      was also a significant sequential decrease of neutrophil percentage between 1
      hour and 4, 8, 12 hours' storage at room temperature (P all < 0.01).

PMID- 10089719
TI  - A path analysis of self-care of elderly women in a rural area of southern Taiwan.
AB  - For rural elderly women in Taiwan, in addition to poor economic situations and
      limited health resources, changing traditional roles and responsibilities and
      changing family structures further aggravate their conditions of health. Self
      care was considered as a strategy or a form of coping to enhance the health and
      quality of life of these women during their aging process. To design an effective
      health-promotion program for elderly women, therefore, understanding their self
      care model is important for health care professionals. The purpose was to use a
      path analysis to test a model of self-care in predicting the direct and indirect
      effects of selected key variables on self-care among rural elderly women. A non
      experimental, cross-sectional study was designed to test the proposed hypotheses
      and the paths in a causal model of self-care. Of the 200 elderly women invited to
      participate, 192 completed all interview questions. The proposed causal model was
      tested with a path analysis, using the LISREL 8 program. The resultant model
      showed that the chi square was 3.65 with four degrees of freedom. The p-value for
      the resultant model was 0.46, revealing that the model fit the data and it was,
      therefore, retained. In addition to the chi 2 test, other fit indices also
      indicate the model fit the data well. In the resultant model, 56.0% of the total
      variance in self-care was accounted for by age, socioeconomic status, perceived
      health status, and social support (p < 0.001); 16.4% of the total variance in
      social support was accounted for by age, socioeconomic status, and marital status
      (p < .001); and 7.3% of the total variance in perceived health status was
      accounted for by social support (p < .001). The implications of nursing practice
      and research were discussed based on the findings.

PMID- 10089720
TI  - Imaging features of simultaneous occurrence of renal and pancreatic foreign body
      granuloma due to chronically retained gauze: a case report.
AB  - Herein we are reporting a case of simultaneous occurrence of renal and pancreatic
      foreign body granuloma due to retained gauze. The different imaging features of
      the two lesions make correct preoperative diagnosis difficult. Foreign body
      granulomas due to retained surgical gauze or sponges should be considered in
      patients who have previous histories of operations and who also have a mass in
      the surgical bed. Simultaneous occurrence of foreign body granuloma away from
      primary surgical field is also possible.

PMID- 10089721
TI  - A mullerian duct remnant myoma misdiagnosed as ovarian cancer in a woman with
      vaginal agenesis--a case report.
AB  - Leiomyoma are very common in the normal uterus; however, they are rather rare in
      mullerian duct remnant. We report a case of mullerian duct remnant leiomyoma
      associated with vaginal agenesis. The mass had papillary growth with cystic-solid
      components by ultrasound. Ovarian cancer was suspected preoperatively. Finally, a
      fibroid with hyalinization and chondroid metaplasia was diagnosed
      histopathologically. To the best of our knowledge, this is the first case of
      mullerian duct remnant leiomyoma with degeneration, mimicking ovarian cancer by
      ultrasound. We provide the clinical details of this case and discuss a diagnostic
      pitfall.

PMID- 10089722
TI  - Red light suppresses N-acetylserotonin but does not elevate 5-HT and 5-HIAA of
      the rat pineal glands at night.
AB  - HPLC with EC detector was used to study the red light effect on the rhythmicity
      of catecholamines (NE, DOPAC and dopamine) and indoleamines (NAS, 5-HT, 5-HIAA)
      in the pineal glands and retinas of the Sprague-Dawley rat. We found the
      prominent nocturnal elevations of NAS in rat pineal glands and the suppression of
      the NAS but not the elevation of 5-HT and 5-HIAA after red light exposure at
      night. Our data show two findings: metabolic pathway of the indoleamines (5-HT, 5
      HIAA and NAS) after red light exposure at night may be different from those by
      white light. Second, the increased HIOMT activity that effects on 5-HT and 5-HIAA
      may also be involved in the indoleamine formation after red light exposure at
      night.

PMID- 10089723
TI  - [Diseases can have social reasons. Neuroendocrine reactions on stress interact
      with immune defense].

PMID- 10089724
TI  - [It is time for physicians to consider the mouth as part of the body].

PMID- 10089725
TI  - [Recruitment with possibility for continuing education--in the backpack!].

PMID- 10089726
TI  - [The reverse side of air bags].

PMID- 10089727
TI  - [Daring health reforms in Zambia].

PMID- 10089728
TI  - [Homocysteine in blood. Deficiency marker and risk marker].

PMID- 10089729
TI  - [Let us not use the anatomical atlas on CD-ROM!].

PMID- 10089730
TI  - [Salvaged femoral heads banked for re-use. Excellent bone replacement in revision
      of prosthetic surgery].
AB  - Morsellized and compacted femoral heads salvaged after hip arthroplasty
      constitute an excellent bone replacement material. Access to this material has
      substantially improved prognosis following replacement of loosened prostheses, a
      finding contrary to previous experience with uncompacted bone grafts and for
      which only hypothetical explanations are available. Although bank bone is a
      material without manifest value beyond its material properties, it is sometimes
      referred to as a transplant, a usage that has resulted in its occasional use
      under the misapprehension that it will promote bone repair, which may cause
      problems. Otherwise, bank bone is more or less innocuous and is not associated
      with a greater risk of viral infection transmission than is blood transfusion.
      The article provides a review of the biological effects to be expected of bank
      bone implants, how the risk of infection can be avoided, and which indications
      are appropriate.

PMID- 10089731
TI  - [New trends in immunodermatology and treatment of skin diseases].
AB  - Nowhere in the body are inflammatory reactions more apparent than in the skin.
      The inflammation may be beneficial, as in defence against tumours or infections,
      or inimical, as in allergy and psoriasis. The skin is a primary immunological
      organ which presents antigens to T cells, and produces many types of cytokines.
      The complex interplay between cells and mediators in immunologically induced skin
      diseases is beginning to be unveiled. Other new developments include improved
      immunosuppressive therapy and highly specific anti-inflammatory treatment that
      induces naturally occurring down-regulatory signals.

PMID- 10089732
TI  - [Somatic complications in anorexia and bulimia nervosa].
AB  - Although the pathogenesis and treatment of anorexia nervosa and bulimia nervosa
      have traditionally been discussed in psychological terms, these eating disorders
      are always accompanied by somatic symptoms, symptoms which may become very
      serious. Moreover, as the anorexic or bulimic patient seeking medical treatment
      does not as a rule reveal the self-inflicted nature of her symptoms to the
      doctor, it is vital that physicians recognize such symptoms as manifestations of
      eating disorders. The article consists in a review of somatic complications
      commonly accompanying anorexia and bulimia, and their relationship to different
      body systems.

PMID- 10089733
TI  - [Gastrointestinal peptides among new therapeutic agents used in type 2 diabetes].
AB  - The pharmacological arsenal available today for the treatment of type II diabetes
      is often insufficient to allow optimal control of the disease. Each agent
      corrects only one or a few of the multiple defects that characterise type II
      diabetes. Currently, new drugs are under development that target several of the
      clinical abnormalities. These agents include the gastrointestinal peptides,
      glucagon-like polypeptide-1 (GLP-1) and amylin, and their analogues. New rapid-
      and long-acting insulin analogues will also constitute interesting treatment
      alternatives.

PMID- 10089734
TI  - [Neuroendocrine disorders cause stress-related disease. "Civilization syndrome"
      is a growing health problem].
AB  - Although the relationship between stress and serious diseases, such as ischaemic
      heart disease, is well known, the underlying mechanisms have proved difficult to
      identify. With a new technique available today, the hypothalamic-pituitary
      adrenocortical axis can be shown to constitute a central physiological factor in
      the interplay between stress and disease. This technique opens up new diagnostic
      possibilities, and thus therapeutic and preventive options, in stress-related
      diseases which represent a growing health problem in modern society.

PMID- 10089735
TI  - [Growing genes cause neurological diseases].
AB  - A growing number of hereditary neurodegenerative disorders have been found to be
      caused by expansion of trinucleotide repeats. A smaller number of diseases such
      as fragile X syndrome, myotonic dystrophy, and Friedreich's ataxia, have been
      found to be due to expansions in non-coding DNA. In a large group of diseases,
      the expansion consists of CAG repeats in the coding region of the gene, producing
      an expanded polyglutamine sequence in the protein. Nine diseases have so far been
      identified as belonging to this group: Huntington's disease, spinobulbar muscular
      atrophy (SBMA), dentatorubral pallidoluysian atrophy (DRPLA), autosomal dominant
      "pure" spastic paraplegia (ADPSP), and five forms of spinocerebellar ataxia (SCA
      1,2,3,6 and 7). Except for SBMA, all of the CAG repeat disorders are
      characterised by autosomal dominant heredity and anticipation (i.e., earlier
      onset age and increasing severity in successive generations). The mutated protein
      causes disease via an as yet unidentified gain-of-function mechanism in specific
      subsets of neurones. Today, DNA analysis permits the diagnosis of a trinucleotide
      disease in individual cases.

PMID- 10089736
TI  - [Mirizzi syndrome. A rare cause of biliary tract obstruction].

PMID- 10089737
TI  - [Mammographic screening does not reduce breast cancer mortality].
AB  - The outcome of a Swedish mammographic screening programme has been studied by
      analysis of official health statistics for 1987-96. The study series comprised
      605,260 women (70 per cent of those aged 50-69 years at inclusion in the
      mammography programme), representing 4,908,176 woman-years, 1,932,353
      mammographies, and 6,713 deaths due to breast cancer. The observed number of
      deaths was 55 (0.8%) less than would have been expected had the screening not
      been performed (ns), whereas findings in the Two County Council study suggest
      that the reduction in mortality should have been 28 per cent (n = 739) for the
      group and period studied. Thus, the cost of saving a single life was estimated to
      have been SEK 18-25 million (approximately GBP 1.3(1.8 m. USD 2.36(3.17 m).

PMID- 10089738
TI  - [Functioning quality assurance system requires and active interest of all
      involved!].

PMID- 10089739
TI  - [Quality audit of health care centers stimulates quality assurance work. It has
      initiated improvements which have been partly accomplished].

PMID- 10089740
TI  - [Scrutiny and comparison of different quality control models].

PMID- 10089741
TI  - [Why does the administrative court of appeal change the appeals of HSAN?++.
      Analysis of 169 cases: milder judgement is common].

PMID- 10089742
TI  - [The Swedish tongs were picked up by an aircraft-messenger].

PMID- 10089743
TI  - [Complications are frequent after surgery for excessive hand sweating. Patient
      should be informed about the risks].

PMID- 10089744
TI  - [Age-related changes in Bruch's membrane in rats].
AB  - PURPOSE: We investigated rats were worth the experimental animal on the aging
      changes in Bruch's membrane. METHODS: We did an ultramicromorphological study on
      the aging changes in Bruch's membrane, in male Sprauge-Dawley rats at 1,6,12 and
      27 months after their birth. RESULTS: With the aging, the basement membranes on
      both sides of Bruch's membrane have become thick. At 6 months of age, the
      basement membranes of the endothelial cells of the choriocapillaris were found to
      be multilayered and cracked and pseudopodia of the endothelium were also observed
      toward the retinal pigment epithelium. At 12 months of age, we found vacuoles in
      the basal portion of the retinal pigment epithelium, as well as fibrillae and a
      part of the process of a cell in the outer collagenous zone correspond with the
      portion of the multilayered and cracked basement membranes of the endothelial
      cells of the choriocapillaris. At the age of 27 months, the basement membranes
      were thicker and a basal laminar deposit was seen. Prominent changes such as
      disappearance of the elastic fibers and increase of the collagenous fibers and
      fibrillae were also seen in some portions. CONCLUSIONS: Thus, the aging changes
      in Bruch's membrane of rats were remarkably reinforced in accordance with the
      age, it were appeared these rats were worth the experimental animal.

PMID- 10089745
TI  - [Changes in Bruch's membrane in experimental hypercholesteremia in rats].
AB  - PURPOSE: We investigated the effect of high cholesterol diet for the aging
      changes in Bruch's membrane of rats. METHODS: After feeding a 4% cholesterol diet
      for 15 weeks to three young rats 3 months old and four aged rats 23 months old,
      we observed the morphological changes of Bruch's membrane by electron microscopy,
      and made a comparison with rats fed an ordinary diet. RESULTS: In one young rat
      fed a high-cholesterol diet, the endothelial basement membrane of the
      choriocapillaris formed multiple folds separated from the plasma membrane of the
      endothelium and showed lamellar thickening and crack in some areas. The elastic
      fiber layer in Bruch's membrane disappeared partly and some new microfibrils
      appeared. In one aged rat fed a high-cholesterol diet, the endothelial basement
      membrane of the choriocapillaris showed more lamellar thickening with lumps in
      some parts. Compared with rats fed an ordinary diet, rats fed a high-cholesterol
      diet showed thickening of the basement membrane and the changes were more severe.
      CONCLUSIONS: Our data indicated that high-cholesterol diet might promote age
      related changes of Bruch's membrane.

PMID- 10089746
TI  - [Scanning electron microscopic studies of the basal surface of the corneal
      endothelium and the stromal and endothelial surfaces of Descemet's membrane in
      rats].
AB  - PURPOSE: The basal surface of the corneal endothelium and the stromal and
      endothelial surfaces of Descement's membrane in rats were studied by scanning
      electron microscopy. METHODS: We compared the fine structures of the two surfaces
      of Descemet's membrane both after sputter-coating with platinum and without
      sputter-coating. RESULTS: Fine structures were made clearly visible without metal
      coating by heating specimens to 300 degrees C during observation. On the basal
      surface of th endothelium, pinocytotic vesicles and invagination of the basal
      cell membrane were visible. After sputter-coating, Descemet's membrane appeared
      to be composed of granular substances. The size of the granules was larger on the
      stromal side than on the endothelial side. Descemet's membrane observed without
      sputter-coating was composed of fine fibrous structures, showing a felt-like
      appearance on both stromal and endothelial sides. The diameter of the fibers on
      the stromal surface was thicker than on the endothelial side. CONCLUSION: These
      results may indicate a characteristic difference between the collagen types
      existing on the two sides of Descemet's membrane.

PMID- 10089747
TI  - [Long-term healing of excimer laser ablated rabbit corneas].
AB  - PURPOSE: To evaluate histologically and immunohistochemically long-term changes
      in rabbit cornea following excimer laser ablation. MATERIALS AND METHODS: Excimer
      laser keratectomy was performed on 12 eyes of 6 rabbits. The corneas were
      subjected to histological and immunohistochemical studies 2 and 3 years after
      treatment. FINDINGS: In all specimens, epithelial basement membrane of the
      ablated central cornea showed undulating and spike-pattern invasion into the
      epithelial side. The collagen lamellae showed irregularities in the subepithelial
      stroma. Immunohistochemically, the subepithelial stroma showed positive reaction
      to anti-type III collagen antibody. Staining for anti-IV collagen antibody showed
      a linear pattern in the epithelial basement membrane and was positive in the
      subepithelial stroma of the ablated central cornea. These positive reactions to
      anti-type III and type IV collagen antibodies in the stroma showed the localized
      presence of scar tissue in the ablated stroma. Antibody to type VII collagen
      showed weak reaction in the basement membrane, suggesting incomplete regeneration
      of anchoring fibrils. CONCLUSION: The healing process was still incomplete 3
      years after excimer laser keratotomy in rabbits.

PMID- 10089748
TI  - [Short-term fluctuation of blue-on-yellow perimetry in normal eyes].
AB  - PURPOSE: To evaluate short term fluctuation (SF) of blue-on-yellow perimetry
      (B/Y) as compared with white-on-white perimetry (W/W) in normal eyes. SUBJECTS
      AND METHOD: One eye each of 25 healthy persons underwent B/Y and W/W perimetry
      repeated 5 times each. The test subjects had no previous experience of perimetry.
      An automated perimeter, Humphrey Field Analyzer, model 750, was used throughout.
      RESULTS: The SF at the first session of B/Y perimetry averaged 2.02 dB. This
      value was significantly different from those of the subsequent 4 sessions. Each
      of SF of B/Y perimetry at the first two sessions was significantly different from
      that of W/W perimetry at the first two sessions. The SF of B/Y perimetry showed
      wider fluctuations than those of W/W perimetry at each session. CONCLUSION: B/Y
      perimetry in normal eyes showed individual differences as well as fluctuations
      between the initial and consecutive sessions. This feature has to be considered
      in interpretation of the findings.

PMID- 10089749
TI  - [Treatment of paralytic esotropia by botulinum type A toxin].
AB  - PURPOSE: The purpose of the present paper is to evaluate the therapeutic effect
      of a single injection of 2.5 U of botulinum Type A Toxin for paralytic esotropia
      resulting from unilateral abducens palsy. MATERIAL: Patients were divided into 3
      groups: acute group of 7 patients 3 to 4 months after onset, chronic group of 6
      patients 5 to 11 months after onset, and a protracted group of 7 patients more
      than one year after onset. Patients less than 3 months after onset were excluded
      because of possible spontaneous recovery. RESULTS: The amount of ocular deviation
      averaged 39.2 delta before and 16.3 delta after treatment. Following treatment,
      good motility and alignment were obtained in 10 patients, including 5 cases in
      the acute group, 4 in the chronic group, and 1 in the protracted group. The
      reduction of deviation averaged 82%, 74%, and 34% in the acute, chronic, and
      protracted groups, respectively. The therapeutic effect was also related to the
      degree of contracture of the medial rectus muscle. Six cases that failed to
      respond to the current therapy underwent surgery for recession/advancement of the
      horizontal muscles. The surgical outcome was not related to the maximum reduction
      obtained by injection of botulinum toxin. CONCLUSION: We conclude that the
      injection should be administered at the end of 3 months after onset, if the
      deviation has not shown any improvement by then. It may be effective in chronic
      cases. Not much improvement can be expected if the condition has persisted for
      one year or longer.

PMID- 10089750
TI  - [Cataract surgery and intraocular lens implantation in patients with Behcet's
      disease].
AB  - PURPOSE: To evaluate the outcome of cataract surgery in patients with Behcet's
      disease. METHODS: The results of 27 eyes of 19 patients with Behcet's disease
      that had undergone cataract surgery with or without intraocular lens implantation
      from October 1993 to December 1996 were retrospectively analyzed. The
      postoperative follow-up period ranged from 13 to 50 months (average, 28 months).
      FINDINGS: Visual acuity improved postoperatively in 25 eyes, to 20/40 or better
      in 9 eyes. In 19 eyes, ocular attacks were seen within the preoperative 6 months
      in 2 eyes, and within the postoperative 6 months in 8 eyes. In 8 eyes, the first
      ocular attacks occurred within 2 months after the surgery. The frequency of
      ocular attacks increased after the surgery in 7 patients who received
      immunosuppressive a gents, with relatively short duration of the disease.
      CONCLUSION: These results suggest that the frequency of ocular attacks increases
      after cataract surgery in some patients who use immunosuppressive agents for
      controlling ocular attacks, even though they had no inflammatory history for a
      long period before the surgery.

PMID- 10089751
TI  - [Warfarin potassium for impending central retinal vein occlusion].
AB  - PURPOSE: We reviewed the records of 10 patients who had impending central retinal
      vein occlusion in order judge whether anticoagulant treatment with warfarin
      potassium (Warfarin) was indicated. PATIENTS: 6 men and 4 women, ranging in age
      from 25 to 83 (average 55) years were studied. RESULTS: Of 6 eyes, retinal
      hemorrhage disappeared completely within 6 months. Four patients whose visual
      acuity was 0.1 or less at one month needed photocoagulation. Four other patients
      whose late venous circulation time at fluorescein angiography improved within 30
      seconds had good visual prognosis, 3 eyes of 4 patients aged 65 or older were not
      successful in regaining their visual acuity. CONCLUSION: Warfarin was not
      effective for patients who had clearly lost their visual acuity and the elderly
      in this series. Late venous circulation time at fluorescein angiography was a
      useful index for this treatment.

PMID- 10089752
TI  - [Histopathological observations on bullous keratopathy after argon-laser
      iridotomy].
AB  - PURPOSE: To elucidate histopathological mechanism of bullous keratopathy after
      argon-laser iridotomy (ALI). CASE AND METHOD: The patient was a 60-year-old
      female who underwent penetrating keratoplasty because of bullous keratopathy
      after 2 years and 2 months of ALI. The corneal specimen was fixed with a mixture
      of 2.5% formalin and 1.0% glutaraldehyde, and examined under light and electron
      microscopes. FINDING AND CONCLUSION: Laser-damaged endothelium produced a large
      amount of basement membrane-like material beneath Descemet's membrane. At the
      next stage, the severely damaged endothelium lost its organellae and cell
      membranes, and fell off. The surrounding healthy endothelium migrated into the
      damaged area and produced a small amount of material like basement membrane which
      covered Descemet's membrane. After that, stromal swelling, decrease of
      keratocytes, breaking and disappearance of Bowman's membrane, epithelial edema,
      connective tissue accumulation beneath basal cells, and epithelial detachment
      occurred in the laser-damaged area.

PMID- 10089753
TI  - [A case of AIDS complicated by progressive outer retinal necrosis].
AB  - BACKGROUND: The retina may be involved in patients with acquired immunodeficiency
      syndrome (AIDS). Progressive outer retinal necrosis (PORN) is a liability. CASE:
      A 46-year-old female had repeated exacerbations of pulmonary tuberculosis since
      two years before. Herpes zoster developed in her right trigeminal nerve area two
      weeks before, leading to a diagnosis of AIDS. She was referred to us for
      ophthalmological evaluation. FINDINGS: Both eyes showed numerous yellowish white
      patches in the deeper retinal layers. The anterior chamber and the vitreous were
      almost intact. Herpes zoster virus was identified in the acqueous by the
      polymerase chain reaction (PCR) method. Systemic acyclovir or ganciclovir failed
      to prevent rapid extension of fundus lesions, resulting in whole-layer necrosis
      of the retina. Retinal detachment with multiple breaks developed in both eyes
      whthin eleven days after the patient was first seen by us. The clinical course
      was different from acute retinal necrosis and was characteristic of PORN.
      CONCLUSION: This case illustrates that PORN may develop in patients affected by
      AIDS.

PMID- 10089754
TI  - [A case of central retinal vein occlusion forming the epiretinal membrane].
AB  - BACKGROUND: We encountered a patient with central retinal vein occlusion (CRVO)
      forming an epiretinal membrane (ERM) in a wide area. Generally formation of ERM
      is rare in CRVO. PATIENT AND METHODS: The patient was a 72-years-old female with
      ischemic CRVO in the right eye, who had undergone insufficient pan-retinal
      photocoagulation. Since ERM was formed in a wide area 7 months after the
      occurrence of CRVO, the patient underwent vitrectomy. RESULTS: Although the
      patient was elderly, the posterior vitreum had not been detached, and ERM was
      observed in a wide area from the disk of the optic nerve over the vascular
      arcade. Since the ERM strongly adhered to the retina, incision of the membrane
      with vitreous scissors was required. The membrane tissue collected during the
      operation showed few vascular and cellular components, and consisted of ERM
      extracellular matrices such as collagen. CONCLUSIONS: In this patient, however,
      it was probable that not only barrier dysfunction of retinal vessel endothelial
      cells caused by elevated pressure in the retinal vein and rapid retinal ischemia
      but also the anatomical feature of the undetached posterior vitreum was involved
      in the formation of the ERM.

PMID- 10089755
TI  - Is a common grouping mechanism involved in the phenomena of illusory continuity
      and stream segregation?
AB  - Two auditory phenomena--stream segregation and illusory continuity through a wide
      band noise interruption--were studied to determine whether the same principles of
      perceptual organization applied to both. A cycle was formed of a repeating
      alternation of two short bursts of narrow-band noise (NBN), one centered at a
      high frequency (H) and the other at a low frequency (L), with shorter bursts of
      wide-band noise (WBN) inserted between successive NBNs (H WBN L WBN H WBN...). In
      some conditions, listeners could hear a single NBN moving up and down behind the
      WBN bursts, although there was no NBN present with the WBN. Listeners rated the
      strength of this illusory continuity. Center frequency separation, rate of
      onsets, and bandwidth of the NBNs were varied. Increases in values of all three
      variables decreased illusory continuity. Other listeners rated the stream
      segregation of the H and L bands when successive NBNs were separated either by
      WBN bursts (as above) or by silences. The same three acoustic variables were
      manipulated. Increases in all three variables decreased the perception of a
      single stream. The similar disruptive effects on illusory continuity and on the
      one-stream percept in the stream segregation task support the idea that both
      phenomena depend on a common preliminary process of linking together the parts of
      a sequence that have similar frequencies.

PMID- 10089756
TI  - Effects of talker, rate, and amplitude variation on recognition memory for spoken
      words.
AB  - This study investigated the encoding of the surface form of spoken words using a
      continuous recognition memory task. The purpose was to compare and contrast three
      sources of stimulus variability--talker, speaking rate, and overall amplitude--to
      determine the extent to which each source of variability is retained in episodic
      memory. In Experiment 1, listeners judged whether each word in a list of spoken
      words was "old" (had occurred previously in the list) or "new." Listeners were
      more accurate at recognizing a word as old if it was repeated by the same talker
      and at the same speaking rate; however, there was no recognition advantage for
      words repeated at the same overall amplitude. In Experiment 2, listeners were
      first asked to judge whether each word was old or new, as before, and then they
      had to explicitly judge whether it was repeated by the same talker, at the same
      rate, or at the same amplitude. On the first task, listeners again showed an
      advantage in recognition memory for words repeated by the same talker and at same
      speaking rate, but no advantage occurred for the amplitude condition. However, in
      all three conditions, listeners were able to explicitly detect whether an old
      word was repeated by the same talker, at the same rate, or at the same amplitude.
      These data suggest that although information about all three properties of spoken
      words is encoded and retained in memory, each source of stimulus variation
      differs in the extent to which it affects episodic memory for spoken words.

PMID- 10089757
TI  - Path completion after haptic exploration without vision: implications for haptic
      spatial representations.
AB  - Subjects haptically explored two legs of a triangular path and responded by
      returning to the origin. Seven conditions were tested, varying in (1) whether the
      path was imaginally displaced between the initial exploration and the response;
      (2) the nature of the displacement, if present--rotation or translation; (3)
      variability in the origin location across trials; and (4) instructions to
      complete a triangle versus remembering the origin location. Mean distance and
      angle responses were modeled by the encoding-error model (Fujita, Klatzky,
      Loomis, & Golledge, 1993), which attributes errors to misencoding of the path
      legs and angle. The model failed to predict the finding of systematic errors in
      response distance but not response angle, a dissociation that held when the path
      was undisplaced or imaginally translated. Rotation before responding produced
      errors more consistent with the model. The data suggest use of a body-centered
      representation to complete undisplaced or imaginally translated paths, but
      adoption of an object-centered representation after imagined rotation, as is more
      consistent with pathway completion using whole-body locomotion.

PMID- 10089758
TI  - Motion in depth: adequate and inadequate simulation.
AB  - We measured errors in estimating the absolute time to collision with a simulated
      approaching textured object. The texture elements were circular bright dots. When
      we matched the rate of angular expansion of the simulated object, the rate of
      expansion of the texture dots, and the rate of increase of dot separation, so as
      to accurately simulate an approaching object, errors were small underestimations
      that were independent of dot size (mean of 3.2%). When dot angular size was held
      constant during the simulated approach, errors were the same as when the
      simulation was accurate, provided that dot size was less than 2.2-4.4 min of arc.
      As dot size was progressively increased, errors changed to overestimations. For
      the largest dot size used (10.5 min of arc at time t = 0), time to collision was
      overestimated by up to 21%. A sufficiently large overestimation would mean that
      measures taken to avoid collision would be too late. We suggest that the
      relevance to everyday life of data on the perception of motion in depth and self
      motion collected using constant-sized dot displays might be questionable if dot
      size exceeds 2.2-4.4 min of arc.

PMID- 10089759
TI  - Visual perception of the relative phasing of human limb movements.
AB  - Studies of bimanual coordination have found that only two stable relative phases
      (0 degree and 180 degrees) are produced when a participant rhythmically moves two
      joints in different limbs at the same frequency. Increasing the frequency of
      oscillation causes an increase in relative phase variability in both of these
      phase modes. However, relative phasing at 180 degrees is more variable than
      relative phasing at 0 degree, and when the frequency of oscillation reaches a
      critical frequency, a transition to 0 degree occurs. These results have been
      replicated when 2 people have coordinated their respective limb movements using
      vision. This inspired us to investigate the visual perception of relative phase.
      In Experiment 1, recordings of human interlimb oscillations exhibiting different
      frequencies, mean relative phases, and different amounts of phase variability
      were used to generate computer displays of spheres oscillating either side to
      side in a frontoparallel plane or in depth. Participants judged the stability of
      relative phase. Judgments covaried with phase variability only when the mean
      phase was 0 degree or 180 degrees. Otherwise, judgments covaried with mean
      relative phase, even after extensive instruction and demonstration. In Experiment
      2, mean relative phase and phase variability were manipulated independently via
      simulations, and participants were trained to perceive phase variability in
      testing sessions in which mean phase was held constant. The results of Experiment
      1 were replicated. The HKB model was fitted to mean judgment standard deviations.

PMID- 10089760
TI  - Enhancing images of facial expressions.
AB  - Facial images can be enhanced by application of an algorithm--the caricature
      algorithm--that systematically manipulates their distinctiveness (Benson &
      Perrett, 1991c; Brennan, 1985). In this study, we first produced a composite
      facial image from natural images of the six facial expressions of fear, sadness,
      surprise, happiness, disgust, and anger shown on a number of different individual
      faces (Ekman & Friesen, 1975). We then caricatured the composite images with
      respect to a neutral (resting) expression. Experiment 1 showed that rated
      strength of the target expression was directly related to the degree of
      enhancement for all the expressions. Experiment 2, which used a free rating
      procedure, found that, although caricature enhanced the strength of the target
      expression (more extreme ratings), it did not necessarily enhance its purity,
      inasmuch as the attributes of nontarget expressions were also enhanced. Naming of
      prototypes, of original exemplar images, and of caricatures was explored in
      Experiment 3 and followed the pattern suggested by the free rating conditions of
      Experiment 2, with no overall naming advantage to caricatures under these
      conditions. Overall, the experiments suggested that computational methods of
      compositing and caricature can be usefully applied to facial images of
      expression. Their utility in enhancing the distinctiveness of the expression
      depends on the purity of expression in the source image.

PMID- 10089761
TI  - Correlational cuing as a function of target complexity and target-flanker
      similarity.
AB  - It is generally assumed that the correlational cuing effect (CE) between targets
      and correlated flankers is due to learning association between the flankers and
      their correlated responses. The present study challenges this view. Experiment 1
      shows that the CE for targets composed of color is eliminated as soon as the
      correlation is removed. Experiment 2 shows that the CE during training is not due
      to association of the flankers with responses. Experiment 3 shows that at least
      some of the CE during training with the correlation is due to repetition priming
      of the display. Experiment 4 replicates the results of Experiment 1 for
      orientation targets. In Experiments 5-7, more typical tasks with letter targets
      are examined, and it is demonstrated that preexperimental similarity between
      targets and correlated flankers is crucial. The CE for correlated but dissimilar
      target-flanker pairs, similar to that for color and orientation targets, is
      confined to on-line processes that occur during training. The CE is transferred,
      however, for correlated and similar target-flanker pairs. We propose that, at
      least for the simple stimulus to response mapping used in our study, the CE is
      not due to learning at all. Instead it is due to (1) on-line processes, such as
      repetition priming, that occur during training with the correlation and (2) a
      regular flanker effect (see, e.g., B. A. Eriksen & C. W. Eriksen, 1974) that
      occurs for similar target-flanker pairs.

PMID- 10089762
TI  - Intra- and cross-dimensional visual search for single-feature targets.
AB  - Cross-dimensional visual search for single-feature targets that differed from the
      distractors along two dimensions (color and orientation) was compared with
      intradimensional search for targets that differed from the distractors along a
      single dimension (either orientation or color). The design of the first three
      experiments differed from those of previous studies in that participants were
      required to respond differently to each of the targets. Experiments 1-3 were
      similar except that in Experiment 1, the distractors were homogeneous; in
      Experiment 2, two types of distractors were used in equal proportions; and in
      Experiment 3, two types of distractors were used but one of the distractors was a
      singleton. The findings, contrary to those of previous studies, revealed that
      cross-dimensional search is at least as efficient and for some targets even more
      efficient than intradimensional search. These results suggest that the details of
      stimulus-to-response mapping are essential in comparing intra- and cross
      dimensional tasks. Experiment 4 used a priming design and did not support an
      explanation based on grouping processes. We outline an explanation for all the
      findings based on a recent cross-dimensional response selection model by Cohen
      and Shoup (1997).

PMID- 10089763
TI  - Attentional localization prior to simple and directed manual responses.
AB  - The relationship between attention and the programming of motor responses was
      investigated, using a paradigm in which the onsets of targets for movements were
      preceded by peripheral attentional cues. Simple (button release) and reaching
      manual responses were compared under conditions in which the subjects either made
      saccades toward the target location or refrained from making eye movements. The
      timing of the movement onset was used as the dependent measure for both simple
      and reaching manual responses. Eye movement latencies were also measured. A
      follow-up experiment measured the effect of the same peripheral cuing procedure
      on purely visual processes, using signal detection measures of visual sensitivity
      and response bias. The results of the first experiment showed that reaction time
      (RT) increased with the distance between the cued and the target locations.
      Stronger distance effects were observed when goal-directed responses were
      required, which suggests enhanced attentional localization of target positions
      under these conditions. The requirement to generate an eye movement response was
      found to delay simple manual RTs. However, mean reaching RTs were unaffected by
      the eye movement condition. Distance gradients on eye movement latencies were
      relatively shallow, as compared with those on goal-directed manual responses. The
      second experiment showed that the peripheral cue had only a very small effect on
      visual detection sensitivity in the absence of directed motor responses. It is
      concluded that cue-target distance effects with peripheral cues are modulated by
      the motor-programming requirements of the task. The effect of the peripheral cue
      on eye movement latencies was qualitatively different from that observed on
      manual RTs, indicating the existence of separate neural representations
      underlying both response types. At the same time, the interactions between
      response modalities are consistent with a supramodal representation of
      attentional space, within which different motor programs may interact.

PMID- 10089764
TI  - Attentional selection of objects or features: evidence from a modified search
      task.
AB  - Three experiments examined the domain of visual selective attention (i.e.,
      feature-based selection vs. object-based selection). Experiment 1 extended the
      requirements of the visual search task by requiring a feature discrimination
      response to target elements presented for short durations (30-105 msec). Targets
      were embedded in 47 distractor elements and were defined by either a distinct
      color or a distinct orientation. Observers made a discrimination response to
      either the target's color or its orientation. When the target-defining feature
      and the feature to be discriminated were the same (matched conditions), accuracy
      was enhanced relative to when these features belonged to separate dimensions
      (mismatched conditions). In Experiment 2, similar results were found in a task in
      which the target-defining dimension varied from trial to trial and observers
      performed both color and orientation discriminations on every trial. The results
      from these two experiments are consistent with feature-based attentional
      selection, but not with object-based selection. Experiment 3 extended these
      findings by showing that the effect is rooted in the overlap between target and
      distractor values in the stimulus set. The results are discussed in the context
      of recent models of visual selective attention.

PMID- 10089765
TI  - Covert signs of expectancy in serial reaction time tasks revealed by event
      related potentials.
AB  - Choice reaction time is strongly determined by the sequence of preceding stimuli.
      With long response-stimulus intervals (RSIs), a cost-benefit pattern is observed,
      which has been related to expectancy, whereas with short RSIs a benefit-only
      pattern emerges, possibly because of automatic facilitation. In the present
      study, event-related potentials were recorded while subjects performed serial
      choice responses to visual and auditory stimuli at long and short RSIs. As
      expected, reaction times displayed cost-benefit and benefit-only patterns at long
      and short RSIs, respectively. In contrast, sequential effects in event-related
      potential amplitudes displayed a cost-benefit pattern, unaffected by the RSI. The
      results demonstrate that an expectancy-like mechanism is always active in serial
      tasks but appears to influence performance only when the RSI is long.

PMID- 10089766
TI  - On the dangers of averaging across observers when comparing decision bound models
      and generalized context models of categorization.
AB  - Averaging across observers is common in psychological research. Often, averaging
      reduces the measurement error and, thus, does not affect the inference drawn
      about the behavior of individuals. However, in other situations, averaging alters
      the structure of the data qualitatively, leading to an incorrect inference about
      the behavior of individuals. In this research, the influence of averaging across
      observers on the fits of decision bound models (Ashby, 1992a) and generalized
      context models (GCM; Nosofsky, 1986) was investigated through Monte Carlo
      simulation of a variety of categorization conditions, perceptual representations,
      and individual difference assumptions and in an experiment. The results suggest
      that (1) averaging has little effect when the GCM is the correct model, (2)
      averaging often improves the fit of the GCM and worsens the fit of the decision
      bound model when the decision bound model is the correct model, (3) the GCM is
      quite flexible and, under many conditions, can mimic the predictions of the
      decision bound model, whereas the decision bound model is generally unable to
      mimic the predictions of the GCM, (4) the validity of the decision bound model's
      perceptual representation assumption can have a large effect on the inference
      drawn about the form of the decision bound, and (5) the experiment supported the
      claim that averaging improves the fit of the GCM. These results underscore the
      importance of performing single-observer analysis if one is interested in
      understanding the categorization performance of individuals.

PMID- 10089767
TI  - Sequential effects in rudimentary auditory and visual tasks.
AB  - Three experiments examined sequential effects in choice reaction time tasks. On
      each trial, a right/left positional judgment was made to a either a pure tone or
      a luminance increment in a visual array of box elements. In the first two
      experiments, a preparatory signal was presented prior to each imperative signal
      to indicate the relevant stimulus modality. At a short stimulus onset asynchrony
      (SOA) between the preparatory and the imperative signal (i.e., 60 msec), subjects
      were quicker to repeat the same response than to change their response when
      presented with successive tones, although no such repetition effect occurred on
      the visual target trials. Subjects were impaired if the stimulus modality changed
      across successive trials regardless of the modality of the target. At a longer
      SOA (i.e., 500 msec), these sequential effects were abolished; subjects were
      assumed to be able to prepare for the relevant modality because of the
      presentation of the preparatory signal. When the preparatory signals were
      omitted, in a final experiment, the modality-switching costs were still evident,
      but now inhibition of return occurred on both the auditory and the visual target
      trials-subjects were now impaired in responding when the target reappeared at its
      immediately previous location. It seems, therefore, that the repetition effect
      and modality-switching effects do dissociate. The data revealed clear differences
      between orienting attention to a particular spatial locale and focusing attention
      to a particular sensory modality.

PMID- 10089768
TI  - [The treatment of diabetic nephropathy. The need for an early diagnosis].

PMID- 10089769
TI  - [The hepatitis C virus: after the track of the human immunodeficiency virus].

PMID- 10089770
TI  - [Renal failure secondary to diabetic nephropathy. A review of the characteristics
      of the diabetic patients who started dialysis in Catalonia in 1994].
AB  - The appearance of diabetic nephropathy and its progression towards renal failure
      can be prevented if an early treatment is instituted. However, diabetes is
      currently one of the main causes of entry into a dialysis program. Therefore, the
      diagnostic characteristics of renal disease in 105 patients who started dialysis
      in Catalonia in 1994 were reviewed; the presence of other changes associated with
      diabetes were assessed. The results showed that 81.7% of patients had proteinuria
      higher than 0.5 g/24 h, and 40.5% had plasma creatinine higher than 5 mg/dl at
      the first nephrological control. As a result, the period between diagnosis of
      nephropathy and the inclusion in the dialysis program was very short (3.7 years)
      and considerably shorter than that reflected in literature for other countries,
      whereas the incidence of other micro and macrovascular complications was similar.
      Remarkably, a high number of smokers and treatment with oral antidiabetic drugs
      (33%) at the end stage of renal failure was observed. These results suggest that
      follow-up of diabetics should be more exhaustive and serial tests be performed to
      detect nephropathy early. An appropriate control during renal failure stage can
      also postpone the disease progression and avoid the appearance of complications
      which at present have a high morbid-mortality and high cost.

PMID- 10089771
TI  - [Thoracic hydatidosis. Our experience in the last 15 years].
AB  - Hydatidosis in Spain has been a relevant public health problem which has been
      partly solved due to the implementation of different preventive programs. In this
      work the thoracic hydatidosis cases diagnosed at our hospital during the last 15
      years are reported. Forty patients with thoracic hydatidosis are analyzed. Most
      of them had pulmonary hydatidosis (32), 14 had liver and lung cysts, and in eight
      cases of thoracic hydatidosis there was no pulmonary involvement; eight patients
      had been operated previously because of hydatidosis. A discussion follows of the
      epidemiologic, clinical and radiologic characteristics, as well as laboratory
      data, endobronchial changes, diagnostic cost/effectiveness of bronchoscopy when
      performed, and results after surgery. To remark the high percentage of
      complicated hydatidosis and uncommon locations, seven cases of multiple
      hydatidosis (two of them with cardiac involvement), five cases had hepato
      thoracic communication, three with chest wall involvement, and one with exclusive
      cardiac involvement, as well as one case of calcified pulmonary hydatidosis. In
      most patients (37), treatment was surgery with a low number of complications at
      post-surgery (3). Three relapses were noted at follow-up.

PMID- 10089772
TI  - [Local control and the esthetic results in the conservative treatment of breast
      cancer. An analysis of 397 consecutive cases].
AB  - Conservative therapy has been the therapy of choice for patients with breast
      cancer in early stage. The results of 397 patients treated with conservative
      therapy and radiotherapy over the breast and lymph node areas (when necessary)
      are analyzed. The results obtained in the different risk groups and according to
      the irradiation mode of the tumoral bed are compared. The likelihood of remaining
      local disease free at 7 years was 94.9 (95% CI: 90.7-99.1). No significant
      differences were observed regarding the mode of overprinting the tumoral bed:
      external radiotherapy or brachytherapy, regarding control and aesthetic result;
      also, no differences were observed between the different risk groups. The
      existence of a subgroup of patients with contraindication for conservative
      therapy is currently not demonstrated.

PMID- 10089773
TI  - [Ketoconazole in the control of arterial hypertension in Cushing's syndrome].
AB  - OBJECTIVE: To determine the usefulness of ketoconazole for the control of
      arterial hypertension (AH) in Cushing syndrome (CS) as temporary treatment.
      PATIENTS AND METHODS: Fifteen cases of CS were collected (eleven cases of Cushing
      disease, two cases of ectopic secretion of ACTH, one case of adrenal adenoma, and
      one case of adrenal carcinoma). The clinical characteristics as well as
      laboratory data of patients with AH and the response to therapy were studied.
      RESULTS: Six patients (40%) had AH. A significant difference was observed of an
      older age, a higher frequency of association with diabetes mellitus and a higher
      24 hour free urine cortisol (FUC) for patients with AH compared with non
      hypertensive patients. Ketoconazole was efficient for controlling AH in five
      cases, and in all of them the return to normal levels of 24 hour FUC was
      achieved. A failure of AH control under treatment with ketoconazole occurred in
      the only case of adrenal carcinoma. There was no significant secondary adverse
      reaction to ketoconazole. CONCLUSIONS: Ketoconazole is an efficient drug for the
      control of AH in CS and is well tolerated. In our series, the return to normal
      levels of FUC was associated with control of AH.

PMID- 10089774
TI  - [Natural-valve endocarditis in patients wearing pacemakers].
AB  - The presence of infective endocarditis with appearance of vegetations over the
      tricuspid valve in patients with permanent pacemaker is an uncommon complication.
      We report here three patients with permanent cardiac pacemakers who developed a
      picture of infective endocarditis over the electrode with appearance of
      vegetations over the native valve. The microorganism recovered from blood
      cultures in the three patients was Staphylococcus. The presence of retained
      pacemaker leads and repetitive surgical procedures over the pacemaker pouch are
      two risk factors reported in literature also present in our patients. Infective
      endocarditis is an uncommon difficult-to-diagnose complication, with a poor
      prognosis and which requires the removal of the whole infected material, with
      implantation of an epidermal pacemaker. Some diagnostic and therapeutic issues
      are discussed.

PMID- 10089775
TI  - [Functional surgery in Parkinson disease: from the anatomic-functional
      organization and physiopathology of the basal ganglia to clinical practice].

PMID- 10089776
TI  - [Recurrent unilateral epistaxis].

PMID- 10089777
TI  - [Hemoptysis and a positive Mantoux in a 28-year-old man].

PMID- 10089778
TI  - [A patient with pancytopenia and a liver mass].

PMID- 10089779
TI  - [A febrile syndrome with bacteremia].

PMID- 10089780
TI  - [Tl-201 SPECT in the diagnosis of primary cerebral lymphoma].

PMID- 10089781
TI  - [An upper digestive hemorrhage due to a gastric heterotopic pancreas].

PMID- 10089782
TI  - [Amphotericin B associated with severe liver toxicity].

PMID- 10089783
TI  - [A case of intense cytolysis following the administration of a hepatitis B
      vaccine].

PMID- 10089784
TI  - [The Budd-Chiari syndrome coinciding with a hemolytic crisis in a patient with
      paroxysmal nocturnal hemoglobinuria].

PMID- 10089785
TI  - Editorial quality, diffusion and bibliometric indicators of the Revista Espaanola
      de Enfermedades Digestivas.
AB  - AIM: To evaluate the editorial quality, diffusion, relevance of the scientific
      content, and the publication practices of the specialised journal Revista
      Espanola de Enfermedades Digestivas. MATERIALS AND METHODS: We checked 136
      parameters based on ISO standards, the recommendations of scientific and
      editorial organisations, and studies of scientific editing and international
      publishing practices for biomedical journals. Diffusion was calculated using
      national and international databases, specialised libraries in Spain, and
      Internet sources. The analysis of the scientific content and publication
      practices was based on bibliometric indicators for the journal, authorship, and
      contributions. The sample for this study comprised six alternate issues of volume
      number 88 (1996), the last issue of this volume, and the first issue of volume 89
      (1997). The samples used for the bibliometric analysis varied depending on the
      characteristics of specific indicators and the availability of information.
      RESULTS: The overall mean value for compliance with standards was 46.1%, while
      the real mean was calculated at 72.21%. The editorial procedures at the journal
      are similar to those of analogous international journals. The Revista Espanola de
      Enfermedades Digestivas is included in international databases of biomedical
      journals, and in the interdisciplinary international database SCI. It was found
      to be present in 70% of the medical libraries of Spanish universities, and in 73%
      of the hospital libraries studied. Bibliometric indicators showed co-authorship
      to be 5.5%; the origin of the authors grouped by province and by type of
      institutional affiliations showed 27.8% of all authors to be from Madrid, and
      that more were affiliated with general hospitals than with university hospitals.
      The mean delay between initial receipt of a manuscript and its publication was
      300 days. Cocitation analysis gave the journal a central position amongst the 38
      Spanish biomedical journals considered representative of the field. The journal's
      impact factor for 1996 was 0.260. CONCLUSIONS: The Revista Espanola de
      Enfermedades Digestivas is a high-quality vehicle of research results, and has
      acceptable internal editorial procedures. The journal is widely distributed,
      though its visibility on the Internet should be improved. Co-authorship is
      similar to that seen in other medical journals. Steps should be taken to make
      this journal better known within Spain, and to reduce the delay between the
      initial receipt and the final publication of manuscripts. Its impact factor is
      increasing steadily.

PMID- 10089786
TI  - Incidence of inflammatory bowel disease in the 02 health area of Castellon (1992
      1996).
AB  - OBJECTIVES: To evaluate the incidence and distribution of inflammatory bowel
      disease (IBD) in the 02 health area of the province of Castellon. METHODS:
      Retrospective study of 133 cases of inflammatory bowel disease (in 72 males and
      61 females aged 13 to 86 years), diagnosed during the period from 1992 to 1996 in
      an eminently rural area with a population of 349,318 inhabitants. RESULTS: The
      incidence of IBD was 9.5 cases/100,000 inhabitants/year (6.8, 1.9 and 0.8
      cases/100,000 inhabitants/year for ulcerative colitis, Crohn's disease and
      indeterminate colitis respectively). Incidence was similar in males and females
      (sex ratio 1.18:1), and average age was 40.9 years (42.6, 35.8 and 38.6 for
      ulcerative colitis, Crohn's disease and indeterminate colitis respectively). The
      predominant clinical forms were rectosigmoiditis in ulcerative colitis,
      granulomatous colitis and terminal colitis in Crohn's disease and
      proctosigmoiditis in indeterminate colitis. CONCLUSION: The incidence and the
      forms of presentation of IBD in the 02 health area of the province of Castellon
      are similar to those reported in the rest of Spain, mainly in the urban
      population.

PMID- 10089787
TI  - Study of gastrointestinal polypeptides controlling gastric acid secretion in
      patients with primary antibody deficiency.
AB  - BACKGROUND: Gastric abnormalities are a common feature in patients with primary
      antibody deficiency. The most important problem is the high incidence of stomach
      cancer found in these patients. Chronic atrophic gastritis with pernicious anemia
      is also a common finding that predisposes to gastric adenocarcinoma. The aim of
      the present study was to identify factors predictive of high risk for developing
      gastric cancer in patients with primary antibody deficiency. PATIENTS AND
      METHODS: We studied gastric hormones (gastrin, somatostatin and gastrin-releasing
      peptide, GRP) in 47 patients (23 children and 24 adults) with primary antibody
      deficiency. In accordance with the World Health Organization (WHO)
      classification, patients were diagnosed as having X-linked agammaglobulinemia
      (Bruton disease) in 13 cases, common variable immunodeficiency in 28, and
      hypogammaglobulinemia with hyperIgM in 6. Gastric biopsy was performed in 22
      patients (16 children and 6 adults). Hormone determinations were carried out by
      radioimmunoassay. RESULTS: Baseline serum gastrin levels were normal or increased
      compared with controls, but the response to stimulation with a hyperproteic diet
      was delayed in 18 patients and lower than in controls in 7. In 4 adult patients,
      all with pernicious anemia, gastric biopsy revealed chronic atrophic gastritis
      involving the stomach corpus and antrum (type B gastritis). The absence of a
      normal response of gastrin secretion to stimulation with a hyperproteic diet may
      be explained by this finding. Serum somatostatin and GRP levels were higher than
      in controls. No correlations were found between these findings and patient age,
      type of immunodeficiency or duration of clinical manifestations.

PMID- 10089788
TI  - [Carcinoid syndrome: advances in diagnosis and treatment].
AB  - Carcinoid is the most common endocrine digestive tumor. The carcinoid syndrome
      resulting from the variety of amines and peptides produced by this tumor is
      usually apparent once there are metastases to the liver. Tumors with direct
      systemic venous drainage seldom produce a carcinoid syndrome without the presence
      of liver metastasis. This may occur because the hormone escapes the normal
      metabolic pathway (monoamine oxidase) in the liver. The most significant and
      important advance in diagnosis for tumor localization has been the introduction
      of scintigraphy using 111In-labeled octreotide. Current management of carcinoid
      syndrome should consider the spontaneous course of the disease and the severity
      of clinical symptoms, and includes different therapeutic options as hepatic
      resection, chemoembolization, medical treatment with the long-acting analogues of
      somatostatin and liver transplantation.

PMID- 10089789
TI  - [Gastrointestinal anisakiasis. Seven cases in three months].
AB  - Human anisakiasis or anisakidosis is an unusual parasitation. During the autumn
      of 1996 seven patients came to our Hospital for such a condition. Five of these
      patients had the parasites in the gastroduodenal area (1 in the gastric body, 3
      in the antrum and 1 in the duodenal bulb, this one with two parasites). Four out
      of the five patients consulted us for intense epigastric pain; only one developed
      a cutaneous rash. The fifth patient was diagnosed unexpectedly during an
      endoscopy appointment. Eosinophilia was detected in none. All the parasites were
      extracted endoscopically and identified as belonging to the Anisakis genera.
      Excepting for the patient with no complaint, the other four showed adhered larvas
      to mucosa. The two other patients were operated because of acute abdominal pain.
      At laparotomy an ileitis was seen and then resected. Under microscopic
      examination both ileon were found to be edematous and infiltrated by eosinophils.
      Anisakis larvae were observed in the submucosa of one of the removed intestines.
      The other patient was diagnosed after an immunologic study consisting of
      radioimmunoassay and Western Blot. Five of the seven patients (71%) acquired the
      parasites after consumption of anchovies with vinegar.

PMID- 10089790
TI  - [Massive lower digestive hemorrhage in Wegener's disease. Reply].

PMID- 10089791
TI  - [Ischemic cholecystitis caused by arterial chemoembolization of hepatocellular
      carcinoma].

PMID- 10089792
TI  - [Salmonella osteomyelitis in a patient with collagenous colitis].

PMID- 10089793
TI  - [Esophago-pleural fistula complicating variceal sclerotherapy].

PMID- 10089794
TI  - [Portosystemic encephalopathy in hereditary hemorrhagic telangiectasia].

PMID- 10089795
TI  - [Traissac voice prosthesis. Apropos of 9 years experiences].
AB  - BACKGROUND: Long term results are discussed. PATIENTS: A retrospective study of 9
      years (1/01/89, 1/01/98) concern 107 laryngectomized patients with 9 patients a
      part from this period, and 30% without prosthesis. Among 80 patients with
      prosthesis, 57% had received primary TEPs (tracheoesophageal puncture), 21%
      delayed primary TEPs and 22% secondary TEPs. Oesophageal voice is always learned
      with tracheoesophageal voice. RESULTS: We find a success rate (1 month) in 75% of
      cases, with a maximum follow up time of 8 years (the average is 3 years 1 month).
      We find a success rate with a long-term result in 66% of cases. Prosthesis
      removal exists in 30% of cases and oesophageal voice is successfull once out of 3
      in this cases. Mean lifetime Traissac's prosthesis is 18 months. After removal,
      non closed fistulas can exist in 40% of cases, and surgery is always successful.
      DISCUSSION: Material Traissac's prosthesis explains extended lifetime.
      CONCLUSION: Traissac's prosthesis gave us satisfaction during a use of 8 years.

PMID- 10089796
TI  - [Voice rehabilitation with a voice prosthesis. Study of 62 patients with 5 years
      follow-up].
AB  - From December 1987 to February 1998, 270 patients underwent a total laryngectomy
      with voice restoration by a voice prosthesis. The analysis is focused on the 62
      live patients with a 5 year follow-up. Tracheoesophageal speech had a success
      rate of 81% after 1 year and 73% after 5 years. The daily use of the voice
      prosthesis is only 68% after 1 year and 61% after 5 years. During the 5 year
      follow up (for all patients) 16 (26%) presented an enlarged fistula with leakage
      around the fistula and 17 (27%) needed a removal of the prosthesis. CONCLUSION:
      Tracheoesophageal speech with a voice prosthesis appears interesting for
      laryngectomized patients with: a high success rate, the quality and precocity of
      the voice obtained. However, it requires extensive care and the results
      deteriorate with time.

PMID- 10089797
TI  - In vitro and in vivo comparison of the low-resistance Groningen and the Provox
      tracheosophageal voice prostheses.
AB  - This study has been performed to evaluate and compare two frequently used
      indwelling tracheoesophageal voice prostheses, the low-resistance (LR) Groningen
      and the Provox voice prosthesis. The airflow resistance in vitro of the Provox
      prosthesis has been measured and compared to our reported results of the LR
      Groningen prosthesis. The in vivo study involved fifteen non-myotomized
      laryngectomees who randomly received one of the two prostheses. Measurements were
      performed of the intratracheal phonatory pressure and of voice parameters. The
      intelligibility of speech in noise was evaluated in eight patients. Patients
      preferences regarding the two prostheses were assessed. Aerodynamic measurements
      show the Provox voice prosthesis to have a lower airflow resistance. The median
      intratracheal phonatory pressure for phonation of 75 dB was significantly lower
      (2.1 kPa) in patients using the Provox voice prosthesis. Speech rate, maximal
      phonation time and maximal vocal intensity showed no significant difference. The
      intelligibility of speech in noise produced with the Provox was significantly
      better than the speech produced with the LR Groningen prosthesis. Subjectively,
      most patients preferred the Provox prosthesis because speech required less
      effort. Patients with a hypotonic pharyngoesophageal segment tended to prefer the
      LR Groningen prosthesis.

PMID- 10089798
TI  - [Comparative intensity-pressure study of patients with a voice prosthesis].
AB  - We have studied the qualities of the voice of the laryngectomized patients and
      theirs possibilities to modify the intensity depending to the pressure. During
      the measurement, it was necessary to explain to the patient how to use the
      material and it was an opportunity to help him in the way to product a voice
      prosthesis. Most of the patients produced a higher intensity with a higher
      pressure. However, some of them obtained high pressures without producing a
      voice. These patients modified the use of the prosthesis or could have an oedema
      for example. In conclusion, these measurements show that there is a relation
      between intensity and pressure but not absolutely in relation with a better voice
      quality.

PMID- 10089799
TI  - [Cholesteatoma in the child].
AB  - 126 children operated on between 1990 and 1996 for a cholesteatoma were followed
      up. In 41 children the posterior wall of the auditory meatus was removed, 85
      children were operated on with posterior tympanotomy via a combined approach
      route. Until now, the amount of cholesteatoma recidive is 16%.

PMID- 10089800
TI  - Facial reanimation after temporal bone fracture.
AB  - Fracture of the temporal bone is usually associated with skull injury and the
      patient is initially seen in the emergency room. As a result the diagnosis of
      facial paralysis may be delayed. The aim of this study is to emphasize the
      importance of early diagnosis and treatment of facial paralysis in such cases.
      Between 1990 and 1996, sixteen patients with facial paralysis due to temporal
      bone fracture were operated on within one month of trauma. The surgical technique
      was selected on the basis of the location of fallopian canal involvement and the
      patients hearing status. Six patients had grade VI, 7 had grade V and 3 had grade
      IV facial weakness preoperatively. Twelve patients had serviceable hearing. 9 of
      them underwent facial decompression through the transmastoid approach and 3 were
      operated on via the middle fossa approach. Four patients with unserviceable
      hearing had the operation through the translabyrinthine route. Postoperatively,
      15 out of sixteen patients gained normal facial function while one had grade III
      facial weakness. Severe grade and sudden onset facial paralysis after temporal
      bone fracture should be surgically corrected as early as possible. The site of
      involvement of the facial canal and patient's hearing status should be considered
      in deciding the type of surgery to be applied.

PMID- 10089801
TI  - Cochlear implant and traumatic lesions secondary to electrode insertion.
AB  - On the basis of data reported in the literature, the authors have attempted to
      define the relationship between the functional results of cochlear implants and
      possible traumatic damage caused by the insertion of electrodes and their support
      into the cochlear bony walls. These findings show that traumatic conditions
      result in functional damage only when they involve the body of Corti's ganglion
      cells or the central part of their axon, whereas functional results are not
      influenced by traumatic damage to the peripheral part of the axon. Traumatic
      damage sustained by other non-nervous structures and the inevitable fibrosis and
      subsequent bone metaplasia processes which occur when a foreign body penetrates a
      living organism also appear to be unimportant.

PMID- 10089802
TI  - Ectopic submandibular thyroid tissue.
AB  - We reported a case of a 66 year-old male patient with a mass located in the right
      submandibular region. Surgical excision of the mass was performed and histologic
      examination revealed that the tumor was ectopic thyroid tissue. Additionally,
      imaging studies confirmed that the thyroid gland was found in its normal location
      and the patient had normal thyroid function testing. In reviewing the literature,
      we found submandibular thyroid tissue to be a rare entity with only 4 cases
      described. We discussed embryologic development of the normal thyroid gland and
      some explanations as to the origins of several forms of ectopic thyroid tissue,
      including that found in the submandibular region.

PMID- 10089803
TI  - [Pathogenic hypothesis of a rare malformation of the stapes].
AB  - We report an exceptional stapedial malformation. The stapes presents here three
      legs. We propose a pathogenic hypothesis with a supernumerary branch of the
      stapedial artery.

PMID- 10089804
TI  - [Maxillary ameloblastoma. Illustration apropos of a clinical case].
AB  - The authors report a case of maxillary ameloblastoma presenting as nasal
      obstruction. An histopathologic description is done. The difference of clinical
      course between intra-osseous and extra-osseous (peripheral) ameloblastoma are
      recalled. The desmoplatic histologic type, recently described in medical
      literature, is exceptional. Surgery remains the adapted treatment in most cases.

PMID- 10089805
TI  - [Three-dimensional facial reconstruction of computerized tomography images by
      computer-aided design: example of an anthropologic study].
AB  - Thanks to the medical scanning techniques and the reliability of some
      applications programs in 3D reconstruction, we are now able to explain an
      observation methodology based on the example of an anthropology study on Egyptian
      mummies'heads through a non-destructive proceeding. We have managed to
      demonstrate the exploration of the cervicofacial anatomy in the three dimensions
      of space and the possibility of dissociating the different anatomical tissues.
      The authors would like to point out the various consequences such a methodology
      may engender in any field.

PMID- 10089806
TI  - ENT aspects of the mummification of the head in ancient Egypt: an imaging study.
AB  - This study of a mummified head from the British museum by high resolution
      computer tomography and 3D reconstruction illustrates, without mutilation of the
      specimen, some aspects of mummification of the head; namely the extraction of the
      brain through the nose and filling the cranium with linen like material, packing
      of the oral cavity and the presence of false eyes. These findings alone allow one
      to date the mummy to no sooner than the 20th dynasty, a time when this custom was
      at its peak. ENT aspects of the mummification of the head are discussed.

PMID- 10089807
TI  - [Geometric modeling and virtual endoscopy of the laryngo-tracheal lumen from
      computerized tomography images: initial applications to laryngo-tracheal
      pathology in the child].
AB  - Endoscopy is an essential stage in the management of laryngo-tracheal disorders
      in the infant, but remains a difficult procedure. CT scanning is used to confirm
      the abnormality and to estimate the degree to which the airway is compromised.
      The authors describe virtual endoscopy of the larynx and trachea based on a
      mathematical model, itself constructed from CT images. This work is based on a
      methodology developed at the Hopital de la Timone for modelling the aorta. By
      applying this methodology to the study of laryngo-tracheal disorders, it is
      possible to establish the relevant pre-treatment measurements (length, diameter,
      degree of narrowing). This preliminary study has been carried out in 8 cases, in
      parallel with their clinical treatment. It has allowed us to single out the 3
      typical examples which are presented in detail, and to show the advantages of
      this new approach: immediate and precise measurements, presentation which it is
      not possible to achieve with conventional techniques of 3-dimensional imaging,
      and demonstration of the degree of encroachment of the externe stenoses. When
      taken as part of the management of the patient, this technique complements the
      findings of real endoscopy, or replaces them, thus reducing the costs of hospital
      admission and the risks inherent in this procedure.

PMID- 10089808
TI  - [Abdominal lymphoma: lymph node and visceral involvemnet].

PMID- 10089809
TI  - [Lymphoma of the gastrointestinal tract].

PMID- 10089810
TI  - [Lymphoma of the urogenital system].

PMID- 10089811
TI  - [Lymphomas of the head and neck].

PMID- 10089812
TI  - [Thoracic lymphoma].

PMID- 10089813
TI  - [Bone lymphoma].

PMID- 10089814
TI  - [Central nervous system lymphoma].

PMID- 10089815
TI  - Structural equation models of sexual harassment: longitudinal explorations and
      cross-sectional generalizations.
AB  - Sexual harassment and its corresponding outcomes develop and change over time,
      yet research on this issue has been limited primarily to cross-sectional data. In
      this article, longitudinal models of harassment were proposed and empirically
      evaluated via structural equations modeling using data from 217 women who
      responded to a computerized questionnaire in 1994 and again in 1996. Results
      indicate that sexual harassment influences both proximal and distal work-related
      variables (e.g., job satisfaction, work withdrawal, job withdrawal) and
      psychological outcomes (e.g., life satisfaction, psychological well-being,
      distress). In addition, a replication of the L. F. Fitzgerald, F. Drasgow, C.L.
      Hulin, M.J. Gelfand, and V.J. Magley (1997) model of harassment was supported.
      This research was an initial attempt to develop integrated models of the dynamic
      effects of sexual harassment over time.

PMID- 10089816
TI  - Can self-reported encoding strategy and recognition skill be diagnostic of
      performance in eyewitness identifications?
AB  - The relationship between 3 witness factors and identification accuracy, as well
      as calibration and diagnosticity of confidence, was investigated. A total of 384
      participants in an eyewitness experiment rated their facial recognition skill,
      general memory skill, and self-reported encoding strategy on a questionnaire
      presented after the photo-confrontation. Participants who rated themselves to be
      good face recognizers showed a slightly higher overall accuracy with a more
      diagnostic confidence-accuracy relation. Participants who reported that they
      relied on a holistic encoding strategy were associated with more accurate
      identifications and a stronger confidence-accuracy relation than those who
      reported an analytic encoding strategy. Degree of self-reported general memory
      skill was not diagnostic of identification performance.

PMID- 10089817
TI  - Effects and timing of developmental peer appraisals in self-managing work groups.
AB  - This study used a repeated measures time-series design to examine the immediate
      and longer term impact of a structured, face-to-face developmental peer appraisal
      on 294 undergraduates in 44 self-managing work groups (SMWGs) and 217 MBA
      students in 36 SMWGs. Results revealed an immediate positive impact on
      perceptions of open communication, task motivation, social loafing, group
      viability, cohesion, and satisfaction. Also, the effects of the peer appraisal
      were not dependent on the perceived ratio of positive to negative feedback, and
      the enduring impact of the appraisal was influenced by its timing relative to
      task deadline. Overall, results emphasized that peer appraisals can have a
      positive effect on relationships and task focus, are influenced by temporal
      context, and have great potential for work teams.

PMID- 10089818
TI  - Photophysical studies on antimalarial drugs.
AB  - Most drugs used in the treatment of malaria produce phototoxic side effects in
      both the skin and the eye. Cutaneous and ocular effects that may be caused by
      light include changes in skin pigmentation, corneal opacity, cataract formation
      and other visual disturbances including irreversible retinal damage (retinopathy)
      leading to blindness. The mechanism for these reactions in humans is unknown. We
      irradiated a number of antimalarial drugs (amodiaquine, chloroquine,
      hydroxychloroquine, mefloquine, primaquine and quinacrine) with light (lambda >
      300 nm) and conducted electron paramagnetic resonance (EPR) and laser flash
      photolysis studies to determine the possible active intermediates produced. Each
      antimalarial drug produced at least one EPR adduct with the spin-trap 5,5
      dimethyl-1-pyrroline N-oxide in benzene: superoxide/hydroperoxyl adducts
      (chloroquine, mefloquine, quinacrine, amodiaquine and quinine), carbon-centered
      radical adducts (all but primaquine), or a nitrogen-centered radical adduct only
      (primaquine). In ethanol all drugs except primaquine produced some
      superoxide/hydroperoxyl adduct, with quinine, quinacrine, and hydroxychloroquine
      also producing the ethoxyl adduct. As detected with flash photolysis and steady
      state techniques, mefloquine, quinine, amodiquine and a photoproduct of
      quinacrine produced singlet oxygen ([symbol: see text]delta = 0.38; [symbol: see
      text]delta = 0.36; [symbol: see text]delta = 0.011; [symbol: see text]delta =
      0.013 in D2O, pD7), but only primaquine quenched singlet oxygen efficiently (2.6
      x 10(8) M-1 s-1 in D2O, pD7). Because malaria is a disease most prevalent in
      regions of high light intensity, protective measures (clothing, sunblock,
      sunglasses or eye wraps) should be recommended when administering antimalarial
      drugs.

PMID- 10089819
TI  - Photogenotoxicity of fluoroquinolones in Chinese hamster V79 cells: dependency on
      active topoisomerase II.
AB  - The Chinese hamster V79 lung cell in vitro micronucleus assay was adapted to
      detect and quantify phototoxicity and photogenotoxicity of fluoroquinolones.
      Using this assay, the quinolones were ranked in terms of decreasing
      phototoxicity: clinafloxacin >> lomefloxacin, sparfloxacin >> trovafloxacin,
      nalidixic acid, ofloxacin, ciprofloxacin > enoxacin, norfloxacin. This rank order
      agrees well with published studies utilizing various other phototoxicity models
      and establishes this approach as a fast and sensitive way to characterize the
      phototoxic potential of quinolones. Nearly complete inhibition of phototoxicity
      was observed if the cells were pretreated for as little as 1 min with 10-20 mM
      sodium azide prior to the addition of quinolone. An identical azide effect was
      seen in unirradiated quinolone- and etoposide-treated cells. These findings are
      consistent with a model in which sodium azide renders DNA topoisomerase II
      catalytically inactive. In this state, topoisomerase II cannot initiate DNA
      strand cleavage and the DNA/topoisomerase complex becomes insensitive to
      quinolones and other topoisomerase II inhibitors. The fact that azide reduces
      both UV-dependent and UV-independent toxicity and clastogenicity strongly
      suggests a common mechanism of toxicity dependent on the formation of
      topoisomerase-induced DNA double-strand breaks.

PMID- 10089820
TI  - Photophysics of melatonin in different environments.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring hormone with a
      structural resemblance to tryptophan. Its fluorescence is solvent dependent and
      strongly quenched in the presence of oxygen. Fluorescence quenching in aqueous
      and organic solutions have been studied in the presence of different quenchers. A
      1: 1 inclusion complex formation between melatonin and different cyclodextrins in
      aqueous solution has been observed. The effects of microheterogeneous media
      provided by cyclodextrins, micelles and reverse micelles on the fluorescence
      characteristics of melatonin have been investigated. The water-soluble inorganic
      quenchers like KBr and KI were unable to quench the fluorescence of melatonin
      dissolved in a microemulsion consisting of surfactant + cyclohexane + 1-propanol
      + water, whereas the organic quenchers like CCl4 and CHCl3 were able to quench
      the fluorescence with a rate constant (on the order of 10(8) dm3 mol-1 s-1) quite
      similar to that in neat organic solvents.

PMID- 10089821
TI  - Subcellular distributions and excited-state processes of hypericin in neurons.
AB  - The photodynamic drug, hypericin, is studied in fetal rat neurons using
      fluorescence microscopy. Hypericin has an extremely high affinity for the cell
      membrane and is found to a smaller extent in the nucleus. Fluorescent excitation
      of hypericin is shown to cause irreversible damage to the cell membranes of
      living neurons. Fixed cells were used to make ultrafast time-resolved
      measurements to avoid the deleterious effects of long-term exposure to intense
      light and room temperatures. To our knowledge, these are the first ultrafast time
      resolved measurements of the fluorescence lifetime of hypericin in a subcellular
      environment. Nonexponential fluorescence decay is observed in hypericin in the
      neurons. This nonexponential decay is discussed in terms of other examples where
      nonexponential decay is induced in hypericin upon its binding to biomolecules.
      The nonradiative processes giving rise to the nonexponential hypericin decay are
      attributed to excited-state electron transfer, excited-state proton transfer or
      both.

PMID- 10089822
TI  - Can cellular phototoxicity be accurately predicted on the basis of sensitizer
      photophysics?
AB  - The phototoxicity of three structurally related photosensitizers (PS),
      deuteroporphyrin IX (DP) and monobromo (Br-DP) and dibromo (Br2-DP) derivatives,
      was studied in murine L1210 leukemia cells. These compounds were chosen on the
      basis of heavy-atom-induced differences in triplet yield, phi T, and lifetime,
      tau T, and used as tools to test a model for phototoxicity based on photophysical
      parameters. All three porphyrins were found to localize preferentially in the
      plasma membrane of L1210 cells by confocal fluorescence microscopy. A poor
      correlation was observed between the measured photodynamic efficacies of these PS
      and a model using photophysical parameters determined by laser flash photolysis
      in homogeneous solution. However, an excellent correlation was obtained when the
      same parameters measured directly in the cells were used. The biological
      microenvironment of the porphyrins in cells induces significant changes in the
      photophysics of the PS. Reduction in fluorescence yield, phi F, and phi T
      observed for Br2-DP in cell suspensions arises from self association of the
      molecule due to increased hydrophobicity and high local concentrations. The
      photophysical model was also tested for its ability to handle variations in the
      oxygen dependence of cellular phototoxicity of these PS. The good correlation
      achieved between laser flash photolysis data determined in cells and the measured
      phototoxicity under air, 1.5% and 0.5% O2-saturated conditions, proves the
      intermediacy of singlet oxygen. This study gives further credence to the direct
      use of photophysical techniques to elucidate photochemical mechanisms in
      biological media while highlighting the potential pitfalls of using solution data
      to predict photosensitizing potential.

PMID- 10089823
TI  - Stratum corneum lipid abnormalities in UVB-irradiated skin.
AB  - Stratum corneum (SC) lipids are of particular importance in maintaining the
      permeability barrier function. Although many studies have demonstrated that UVB
      irradiation of mammalian skin reduces barrier function, the responsible
      alterations in SC lipid profiles are not known. In this study, we investigated
      both compositional and morphological alterations in SC lipids with the
      development of barrier abnormalities caused by daily UVB irradiation in hairless
      rat skin. The UVB irradiation of suberythemal doses (0.5 minimal erythema dose)
      significantly increased transepidermal water loss (TEWL) relative to
      nonirradiated control, indicating a diminished barrier function. Under these
      conditions, the total amounts of major SC lipid species (ceramides, cholesterol,
      free fatty acids) in UVB-irradiated SC did not differ from those in nonirradiated
      SC. However, electron microscopic observations revealed marked abnormalities in
      the intercellular domains of UVB-irradiated SC, where naturally occurring
      intercellular multilamellar structures were often absent and leaving the area
      with the appearance of an empty space. Moreover, in UVB-irradiated SC, individual
      corneocytes often showed small amounts of intercellular deposition product with
      abnormal lamellar structure, where lamellar body sphingomyelinase activity was
      present. These observations demonstrated a partial failure of lamellar body
      secretion in UVB-irradiated SC and suggested that a defect in the secretion of
      lamellar body-derived lipids and enzymes to SC intercellular space is, at least
      in part, responsible for the observed abnormal intercellular structure and
      barrier disruption.

PMID- 10089824
TI  - Photooxidized products of recombinant alpha A-crystallin and W9F mutant.
AB  - Human lenses contain many photosensitizers that absorb light at wavelengths above
      300 nm, most notably UVA light (320-400 nm). Kynurenine (Kyn) and 3
      hydroxykynurenine (HK), two of the best-known photosensitizers in the human lens,
      may play a significant role in photooxidation-related changes in lens proteins,
      such as conformational change and aggregation. In vitro irradiation experiments
      with proteins indicate that the Trp residue (with maximal absorption at 295 nm)
      is more susceptible to photooxidation by UVB light (280-320 nm) than by UVA
      light, but most UVB light below 300 nm is screened by the cornea and little
      reaches the lens, especially the nuclear region where nuclear color develops.
      Therefore, if photooxidation is an important contributor to nuclear color or
      nuclear cataract, it must arise from a photosensitized reaction. In the present
      study, we use recombinant alpha A- and its Trp-deficient mutant W9F as models to
      study the effects of UVA irradiation in the presence of HK or Kyn and of UVB (300
      nm) irradiation on alpha-crystallins. alpha A-crystallin showed a large decrease
      in Trp fluorescence and a large increase in non-Trp (blue) fluorescence after the
      HK-sensitized or 300 nm photooxidation. For the W9F mutant, a smaller decrease in
      protein fluorescence (lambda ex at 280 nm) and a smaller increase in blue
      fluorescence than for the wild-type alpha A-crystallin were observed. A decrease
      in the near-UV CD was also observed for both photooxidized alpha A and the W9F
      mutant. The effect of Kyn sensitization is smaller than that of HK sensitization.
      A study of chaperone-like activity indicated that only 300 nm photooxidized alpha
      A and the W9F mutant increased the ability to protect insulin from dithiothreitol
      induced aggregation. Thus, sensitized photooxidation can occur in amino acids
      other than Trp by UVA in the presence of HK or Kyn with effects similar to,
      albeit smaller than, those of direct UVB (300 nm) photooxidation.

PMID- 10089825
TI  - Detection of colonic malignant lesions by digital imaging of UV laser-induced
      autofluorescence.
AB  - The objective of our study was to investigate whether digital imaging of
      autofluorescence could be applied in the detection of colonic malignancies.
      Autofluorescence was excited with a 325 nm line from a He-Cd laser. Images were
      recorded in vitro in six spectral bands. The material for study was 50 resected
      specimens for which images of 64 areas were recorded. The main result is the
      observation that for a majority of malignant and premalignant lesions the
      intensity of autofluorescence was lower than for the corresponding normal mucosa
      in all of the spectral bands selected for imaging. The spectral bands centered
      around 440 nm and 475 nm seem to be most promising in terms of possible future
      clinical applications.

PMID- 10089826
TI  - Salt water bathing prior to UVB irradiation leads to a decrease of the minimal
      erythema dose and an increased erythema index without affecting skin
      pigmentation.
AB  - The combination of salt water baths and solar radiation is known as an effective
      treatment for patients with psoriasis and atopic dermatitis. To determine whether
      increased susceptibility to UVB radiation may contribute to this therapeutic
      effect we have studied the effect of bathing the skin in salt water prior to UVB
      irradiation. Twelve subjects were phototested on the volar aspects of their
      forearms with increasing doses of UVB radiation. One forearm was exposed to 5%
      salt water prior to irradiation. The minimal erythema dose (MED) was determined
      and the erythema index and skin pigmentation were assessed by photometric
      measurement. The combination of salt water bath and irradiation yielded a
      significant decrease of the MED when compared to UVB alone (median 90 mJ/cm2 vs
      130 mJ/cm2, P < 0.01). Analysis of variance showed a significant influence of
      salt water bath on erythema (P < 0.05) but not on skin pigmentation. Within the
      MED test area the erythema index of the salt water exposed forearms was elevated
      significantly (P < 0.05) while skin pigmentation was not affected. Thus, bathing
      the skin in salt water leads to a decreased threshold level for the elicitation
      of UVB-induced erythema and a selective increase of the erythemal response. This
      sensitization to the effects of shortwave UVB radiation may increase
      immunosuppressive effects of UVB radiation and may lead to an increased efficacy
      of UVB phototherapy. However, there is also an increased sunburn risk when salt
      water baths are followed by exposure to UV radiation.

PMID- 10089827
TI  - Receptor-mediated targeting of phthalocyanines to macrophages via covalent
      coupling to native or maleylated bovine serum albumin.
AB  - Targeted delivery of aluminum tetrasulfophthalocyanine (AlPcS4) to the scavenger
      receptor of macrophages, via coupling to maleylated bovine serum albumin (mal
      BSA), was explored as a means to improve photodynamic efficacy. The AlPcS4 was
      covalently coupled to BSA (9:1 molar ratio) via one or two sulfonamide-hexanoic
      amide spacer chains, followed by treatment with maleic anhydride to yield the mal
      BSA-phthalocyanine conjugates. The latter were tested for singlet oxygen
      production, receptor-mediated cell uptake and phototoxicity toward J774 cells of
      macrophage origin and nonphagocytic EMT-6 cells. Cell uptake of 125I-mal-BSA
      showed specific binding for J774 cells but not for EMT-6 cells. Competition
      studies of the conjugates with 125I-mal-BSA showed that coupling of AlPcS4 to BSA
      resulted in recognition of the conjugate by the scavenger receptor, whereas
      coupling to mal-BSA further enhanced its binding affinity. This suggests that
      affinity for the scavenger receptor is related to the overall negative charge of
      the protein. Phototoxicity of the conjugates toward J774 cells paralleled their
      relative affinity, with mal-BSA-AlPcS4 coupled via two spacer chains showing the
      highest activity. The conjugates were less phototoxic toward the EMT-6 cell line.
      The activities in both cell lines of all conjugated AlPcS4 preparations were,
      however, lower than that of the free disulfonated AlPcS2. Possible implications
      for the in vivo use of protein-photosensitizer conjugates to target selectively
      various macrophage-associated disorders is discussed.

PMID- 10089828
TI  - Inhibition of various steps in the replication cycle of vesicular stomatitis
      virus contributes to its photoinactivation by AlPcS4 or Pc4 and red light.
AB  - Vesicular stomatitis virus (VSV) was used as a model virus to study the processes
      involved in photoinactivation by aluminum phthalocyanine tetrasulfonate (AlPcS4)
      or silicon phthalocyanine HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc4) and red light.
      Previously a very rapid decrease in the intracellular viral RNA synthesis after
      photodynamic treatment was observed. This decrease was correlated to different
      steps in the replication cycle. Binding of VSV to host cells and internalization
      were only slightly impaired and could be visualized by electron microscopy. The
      capability of the virus to fuse with membranes in an acidic endosomal environment
      was studied using both pyrene-labeled liposomes and a hemolysis assay as a model.
      These tests indicate a rapid decrease of fusion capacity after AlPcS4 treatment,
      which correlated with the decrease in RNA synthesis. For Pc4 treatment no such
      correlation was found. The fusion process is the first step in the replication
      cycle, affected by AlPcS4 treatment, but also in vitro RNA polymerase activity
      was previously shown to be inhibited. Inactivation of VSV by Pc4 treatment is
      apparently caused by damage to a variety of viral components. Photodynamic
      treatment of virus suspensions with both sensitizers causes formation of 8-oxo
      7,8-dihydroguanosine in viral RNA as measured by HPLC with electrochemical
      detection. This damage might be partly responsible for inhibition of the in vitro
      viral RNA polymerase activity by photodynamic treatment.

PMID- 10089829
TI  - The high photoactivity of m-THPC in photodynamic therapy. Unusually strong
      retention of m-THPC by RIF-1 cells in culture.
AB  - 5,10,15,20-Tetra(m-hydroxyphenyl)chlorin (m-THPC, Foscan) is an extremely
      powerful photosensitizer showing up to 200 times the photodynamic activity of
      Photofrin in patients, in terms of drug/light dose. The influence of treatment
      conditions on the photodynamic efficacy of m-THPC has been compared to
      polyhematoporphyrin (PHP), a Photofrin equivalent, and a cationic pyridinium zinc
      (II) phthalocyanine (PPC), using the RIF-1 cell line. As predicted, the presence
      of serum during sensitizer incubation reduced the photodynamic efficacy of all
      three sensitizers. However, the presence of serum during the illumination period
      only had an inhibitory effect with PHP and PPC but not m-THPC. Quantification of
      the intracellular levels of sensitizer revealed that this was due to the efflux
      of PPC and PHP but not m-THPC into the medium, suggesting that m-THPC is tightly
      sequestered on entering the cell. This may partially explain the high efficacy of
      m-THPC in clinical photodynamic therapy and also highlights the importance not
      only of incubation conditions but also illumination conditions when in vitro
      comparisons are performed.

PMID- 10089830
TI  - Dependence of fibroblast autofluorescence properties on normal and transformed
      conditions. Role of the metabolic activity.
AB  - The dependence of autofluorescence properties on the metabolic and functional
      engagement and on the transformation condition was studied on single cells.
      Normal Galliera rat fibroblasts at low subculture passage (cell strain), at high
      subculture passage (stabilized cell line), and transformed cell line derived from
      a rat sarcoma were used as a cell model. The study was performed by
      microspectrofluorometric and fluorescence imaging technique. The autofluorescence
      properties of cells were studied by excitation at two wavelengths, namely 366 nm
      and 436 nm, that are known to favor the emission of different fluorophores.
      Spectral shape analysis indicated that under excitation at 366 nm
      autofluorescence is ascribable mainly to coenzyme molecules, particularly to
      reduced pyridine nucleotides, while under excitation at 436 nm, flavin and
      lipopigment emission is favored. The energetic metabolic engagement of the
      different cell lines was analyzed in terms both of parameters related to
      anaerobic-aerobic pathways (biochemical assay) and of mitochondrial features
      (supravital cytometry). The results showed that the cell strain and the
      stabilized and transformed cell lines can be distinguished from one another on
      the basis of both overall fluorescence intensity and the relative contributions
      of spectral components. These findings indicated a relationship between
      autofluorescence properties and energetic metabolism engagement of the cells
      that, in turn, is dependent on the proliferative activity and the transformed
      condition of the cells. In that it is a direct expression of the energetic
      metabolic engagement, autofluorescence can be assumed as an intrinsic parameter
      of the cell biological condition, suitable for diagnostic purposes.

PMID- 10089831
TI  - Protoporphyrin IX-sensitized photoinactivation of 5-aminolevulinate-treated
      leukemia cells: effects of exogenous iron.
AB  - Photodynamic therapy with 5-aminolevulinic acid (ALA) is based on metabolism of
      ALA to a photosensitizing agent, protoporphyrin IX (PpIX), in tumor cells.
      Photosensitivity of target cells may be influenced by mitochondrial iron levels
      because ferrochelatase-catalyzed insertion of Fe2+ into PpIX converts it to heme,
      a nonsensitizer. To investigate this prospect, we exposed L1210 cells
      (approximately 10(6)/mL in 1% serum-containing medium) to a lipophilic iron
      chelate, ferric-8-hydroxyquinoline (Fe[HQ]2, 0.5 microM), prior to treating with
      ALA (0.2 mM, 4 h) and irradiating with broadband visible light. When Fe(HQ)2 was
      added to cells immediately or 1 h before ALA, the initial rate of photokilling,
      as measured by thiazolyl blue (mitochondrial dehydrogenase) assay, was markedly
      less than that of non-iron controls. The HPLC analysis of cell extracts indicated
      that ALA-induced PpIX was at least 50% lower after this Fe(HQ)2 treatment,
      presumably explaining the drop in photolethality. By contrast, cells treated with
      ALA and light 20 h after being exposed to Fe(HQ)2 contained the same amount of
      PpIX as non-iron controls and were photoinactivated at nearly the same rate. The
      20 h delayed cells contained approximately 12 times more immunodetectable
      ferritin heavy subunit than controls or 1 h counterparts, which could account for
      the disappearance of iron's antisensitization effects in the former. Consistent
      with this idea, the short-term effects of Fe(HQ)2 on ALA-induced sensitization
      were found to be blunted significantly in ferritin-enriched cells. The Fe(HQ)2
      produced strikingly different results when cells were sensitized with exogenous
      PpIX, stimulating photokilling after short-term contact but inhibiting it after
      long-term contact while having no significant effect on the level of cell
      associated PpIX in either case. Thus, iron can have diverse effects on PpIX
      mediated photokilling, depending on contact time with cells and whether the
      porphyrin is metabolically derived or applied as such.

PMID- 10089832
TI  - Laser-induced fluorescence (LIF) recognition of the structural composition of
      porcine heart valves.
AB  - Reconstruction and replacement of heart valves with grafts fro pig tissue is a
      common procedure. However, bioprosthetic valves wear out in a shorter time span
      than mechanical valves. Bioprosthetic valve structure may contribute to
      degenerative changes that lead to valve failure. There is, at present, no method
      to examine the structure of a tissue valve prior to implant. Laser-induced
      fluorescence (LIF) of natural fluorophores is an elegant method developed for the
      detection of tumors, dermal lesions and atherosclerosis. We have studied LIF as a
      potential diagnostic technique for analysis of valvular tissue. Using excimer
      laser excitation, we examined natural fluorescence recorded from porcine aortic,
      mitral and pulmonary valves. All three valve outflow surface tissue layers are
      less fluorescent at 390-450 nm than the inflow layers. Immunohistochemical
      analysis of collagen I and elastin content in inflow and outflow surface layers
      of all three valves correlated well with LIF intensities and dI/d lambda values
      at selected wavelengths. In conclusion, the differences observed in emitted LIF
      from valve surface layers are found to correlate well with diversity in the
      structural protein content. The LIF spectroscopic measurements may provide an
      appropriate tool for examination of tissue valve structure prior to use for
      implantation.

PMID- 10089833
TI  - Navigation in the mega-trials waters: reflections on the Multicenter Automatic
      Defibrillator Implantation Trial and the Antiarrhythmics Versus Implantable
      Defibrillators Study.
AB  - Today, cardiology seems to be driven by mega-trials and meta-analyses. Guidelines
      published by scientific and professional cardiovascular societies, such as the
      American Heart Association, the American College of Cardiology, and the European
      Society of Cardiology, follow the rules of evidence-based medicine. Such evidence
      is not always sufficiently conclusive to practice clinically helpful medicine.
      Sometimes, relatively small trials, such as the Multicenter Automatic
      Defibrillator Implantation Trial and the Antiarrhythmics Versus Implantable
      Defibrillators study, may be taken as guides for current clinical decisions and
      as inspiration for future investigations. Large mega-trials with a great lack of
      homogeneity among the recruited patients are less important for clinically
      helpful medicine than studies enrolling well-defined, high-risk patients. It is
      probably important to acknowledge that the best possible treatment for many
      patients with ventricular tachyarrhythmias remains obscure. Among these
      situations are the following: (1) sustained ventricular tachycardia (VT) in
      patients without coronary artery disease; (2) sustained, nonsyncopal VT in
      patients with coronary artery disease and left ventricular dysfunction; (3) post
      myocardial infarction survivors with an ejection fraction < or = 35%,
      frequent/complex ventricular arrhythmias, depressed heart rate variability, and
      inducible sustained ventricular tachyarrhythmias during electrophysiologic study.
      Many studies are being conducted to add light where uncertainty exists, but
      probably only a few will contribute to the practice of clinically helpful
      medicine, although some will be used to produce meta-analysis to sustain evidence
      based medicine.

PMID- 10089834
TI  - Single-chamber versus dual-chamber implantable cardioverter defibrillators:
      indications and clinical results.
AB  - The clinical benefit of standard (single-chamber) implantable cardioverter
      defibrillator (ICD) therapy in elderly patients or in subjects with moderate or
      severe heart failure who had ventricular tachyarrhythmias has been debated. We
      studied the follow-up of 450 patients who underwent standard ICD implantation at
      our institution in relation to the functional status of heart failure (New York
      Heart Association Class) or patient's age. During a mean follow-up of 24 +/- 28
      months (range, < 1-114 months), 90 patients (23%) died: 9 patients (2%) from
      sudden arrhythmic death and 5 patients (1%) suddenly, but probably not from
      arrhythmic causes; 55 patients (14%) died from congestive heart failure and/or
      myocardial reinfarction and 21 patients (5%) from noncardiac causes. We could
      clearly demonstrate that ICD therapy was able to prevent sudden cardiac death,
      both in patients with severely depressed left ventricular function and in
      patients aged > or = 65 years. An important step forward in ICD technology was
      the introduction of dual-chamber pacing possibilities to improve left ventricular
      dysfunction and to allow a more individualized ICD therapy. At our institution,
      we have implanted a dual-chamber ICD in 15 patients. Preliminary results showed
      that heart failure improved in 5 patients (33%) and remained unchanged in 10
      patients (67%, p = not significant). There were no patients who had a lesser
      degree of heart failure after implant. Based on our experience so far, in
      addition to the hemodynamic benefits of dual-chamber ICDs, dual-chamber sensing
      and wave-form storage capabilities are very helpful and promising diagnostic
      tools for the detection and handling of inappropriate ICD therapies.

PMID- 10089835
TI  - What is the ideal rate-adaptive sensor for patients with implantable cardioverter
      defibrillators: lessons from cardiac pacing.
AB  - The development of implantable pacemakers in the clinical setting mirrors the
      implementation of advanced technical possibilities. In the United States, 83% of
      all pacemakers implanted in 1996 had rate response as a programmable option. A
      variety of sensors have been proposed and used for rate control. Among today's
      many concepts, accelerometer-controlled pacing is the most widely used rate
      adaptive principle. Although the use of a second sensor is currently of proven
      benefit for only a limited number of patients, the concept of closed-loop pacing-
      implementing a negative feedback between pacing rate and the control signal-
      merits further investigation. This is of special importance in defibrillator
      patients whose myocardial contractility is generally limited. These patients are
      most sensitive to pacing rates that are too high for a given metabolic situation.
      The integration of rate-adaptive pacing into defibrillators is a natural
      consequence of the technical evolution.

PMID- 10089836
TI  - Energy levels for defibrillation: what is of real clinical importance?
AB  - Today, transthoracic and intracardiac defibrillation offer a well-accepted and
      widely used form of therapy for patients with life-threatening ventricular
      arrhythmias. Despite the wide clinical use of defibrillators, the mechanisms by
      which an electrical shock halts fibrillation are still not completely understood.
      During a shock, different amounts of current flow through the different parts of
      the heart and the current distribution is highly uneven. This current
      distribution is affected by changes in the shock potential gradient through the
      heart, changes in fiber orientation, and changes in myocardial conductivity
      caused by connective tissue barriers. It would be ideal if the potential gradient
      distribution throughout the ventricles could be measured directly for each
      individual patient during defibrillator implantation and follow-up and the shock
      strength could be programmed based on this measurement, but so far this is not
      possible. A more feasible approach is to determine, by trial and error, the
      magnitude of the shock strength delivered through the defibrillation electrodes
      for successful defibrillation. There is no distinct threshold value above which
      all shocks succeed and below which all shocks fail to defibrillate. Rather,
      increasing shock strength increases the likelihood the shock will succeed.
      Therefore, instead of a distinct defibrillation threshold, a probability of
      success curve exists. However, increasing the shock strength above an optimal
      range can actually decrease the success rate for defibrillation. One possible
      explanation is that the high voltage gradients caused by such large shocks damage
      cells and result in postshock arrhythmias that may reinitiate fibrillation.
      Another problem that can affect the probability of defibrillation success for a
      particular programmed energy setting is that the shock strength required for
      defibrillation may increase over time due to (1) the growth of fibrotic tissue
      around the defibrillation electrode; (2) migration of the lead; (3) acute
      ischemia; or (4) other changes in the underlying cardiac disease (e.g., worsening
      of heart failure). Such possible increases in the defibrillation shock strength
      requirement should be compensated for before they occur by adding a margin of
      safety to the shock strength needed for effective defibrillation. When
      programming an implantable defibrillator, it is important to keep in mind that
      the defibrillation shock should be (1) strong enough to defibrillate at least 98%
      of the time with the first shock; (2) weak enough not to cause severe post-shock
      arrhythmias or reinitiation of fibrillation; but (3) strong enough to compensate
      for changes of defibrillation energy requirements over time. This usually can be
      accomplished by setting the defibrillator 7-10 J higher than the defibrillation
      threshold determined by a standard step-down protocol.

PMID- 10089837
TI  - Safety and efficacy of implantable defibrillator therapy with programmed shock
      energy at twice the augmented step-down defibrillation threshold: results of the
      prospective, randomized, multicenter Low-Energy Endotak Trial.
AB  - Whether the safety and efficacy of implantable cardioverter defibrillator (ICD)
      therapy can be assured with lower output devices is an important question. The
      purpose of this study was to evaluate whether programming the device output at
      twice the augmented defibrillation threshold was as safe and effective as using
      the maximum energy. Patients indicated for ICD therapy, but without slow
      monomorphic ventricular tachycardia (MVT), who achieved an augmented
      defibrillation threshold (DFT plus) < or = 15 joules (J) with a single
      endocardial lead system and a biphasic defibrillator were included in the study.
      Prior to ICD implantation, patients were randomized into 2 groups. The shock
      energies in test group patient were set as follows: first shock at twice DFT
      plus, the second to fifth shocks at maximum output (34 J). In control group
      patients, all shocks were programmed at 34 J. The study population consisted of
      166 consecutive patients (mean age 57.4 +/- 12.1 years, mean left ventricular
      ejection fraction 36.8 +/- 13.8%). Mean DFT plus was 9.6 +/- 3.2 J in test group
      patients and 10.1 +/- 3.5 J in control group patients (p = 0.36). During a mean
      follow-up of 24.2 +/- 9.6 months, 736 arrhythmia episodes were analyzed. The
      first shock efficacy was 98.3% in the test group patients versus 97.4% in the
      control group (p = 0.45). Total mortality was 6%, equally distributed in both
      study groups. The results of this study prove that the method of doubling the
      defibrillation energy at the DFT plus level provides an adequate safety margin in
      defibrillator therapy.

PMID- 10089838
TI  - Is inappropriate therapy a resolved issue with current implantable cardioverter
      defibrillators?
AB  - Patients with an implantable cardioverter defibrillator (ICD) can undergo
      inappropriate therapies if electrical activity not originating in the ventricle
      is wrongly recognized as ventricular by the device. Inappropriate therapy can be
      the result of detection of supraventricular tachycardias or over-sensing of other
      artifacts by the device. Enhanced detection criteria in third-generation ICD have
      been implemented to recognize fast supraventricular arrhythmias. Analysis of the
      use of these criteria in patients with an ICD has shown that arrhythmias detected
      in the ventricular tachycardia zone are frequently supraventricular (193
      supraventricular of 690 tachycardia episodes in 23 of 59 patients). Use of sudden
      onset was very effective in detecting sinus tachycardia (65 of 67 episodes) and
      stability was very useful in detecting atrial fibrillation (31 of 32 episodes).
      However sensitivity in detecting ventricular tachycardia was only 90% (451 of 497
      episodes). Application of the sustained, rate duration criteria allowed
      appropriate treatment of all ventricular tachycardia episodes, increasing
      sensitivity to 100%; however, specificity in appropriate nontreatment of
      supraventricular episodes decreased from 96% to 83%. Subsequent analysis of
      different algorithms showed that sudden onset > 9% and stability < 40 msec was
      the algorithm with the best specificity and sensitivity. Programming sudden onset
      and stability detection criteria with a sustained, rate duration safety net for
      triggering tachycardia therapy results in appropriate device management in most
      patients with supraventricular and relatively slow ventricular tachycardia.

PMID- 10089839
TI  - Algorithm for the prevention of ventricular tachycardia onset: the Prevent Study.
AB  - The Prevent Study is designed to investigate the effect of a rate-smoothing
      algorithm on the onset of ventricular tachycardia in patients with implanted
      cardioverter defibrillators (ICD) with dual-chamber pacing and sensing function.
      Included in the study are patients who require ICD therapy for recurrent
      ventricular tachycardia or aborted cardiac arrest. After giving informed consent
      to the study, the patients receive a Ventak AV ICD (CPI-Guidant, St. Paul, MN).
      The patients are randomized to start either with active or inactive rate
      smoothing algorithm. After 3 months, all patients cross over to the opposite
      group. Questionnaires are used to investigate quality-of-life issues. A total of
      240 patients will be enrolled in the study, with a minimum follow-up of 6 months.

PMID- 10089840
TI  - A preview of implantable cardioverter defibrillator systems in the next
      millennium: an integrative cardiac rhythm management approach.
AB  - The implantable cardioverter defibrillator (ICD), a primary therapeutic option
      for preventing sudden cardiac death, has rapidly evolved since being introduced
      clinically in 1980. Technologic advances in several key areas have enabled ICDs
      to provide more sophisticated rhythm management. Recent emphasis has been placed
      on dual-chamber ICDs possessing adaptive-rate pacing capabilities. Adoption of
      dual-chamber ICD systems has been rapid. The capabilities of future ICD systems
      will be governed by an integrative strategy that brings together sets of features
      specifically targeted at multifaceted rhythm disorders. The addition of atrial
      therapy will require more sophisticated rhythm discrimination algorithms. ICD
      technology will improve on several fronts including leads, integrated circuits,
      batteries, and capacitors. Additionally, state-of-the-art pacemaker technology
      will continue to be incorporated into ICDs. As these new ICD systems become
      increasingly sophisticated from an engineering viewpoint, tremendous emphasis
      will be placed on decreasing the complexity of programming, device interrogation,
      and patient monitoring during routine patient follow-up. Vast improvements in ICD
      programming systems may ultimately permit the 1-minute follow-up.

PMID- 10089841
TI  - Amiodarone and "primary" prevention of sudden death: critical review of a decade
      of clinical trials.
AB  - Several trials have evaluated the role of amiodarone in decreasing mortality in
      patients at high risk of developing sudden death. Current evidence does not
      support the prophylactic use of amiodarone in myocardial infarction (MI)
      survivors with a depressed left ventricular function and/or frequent or complex
      ventricular ectopy. Some postinfarction trials (e.g., the Spanish Study of Sudden
      Death [SSSD]) found mortality rates in controls much lower than the expected
      figures. Other postinfarction trials--the European Amiodarone Myocardial
      Infarction Arrhythmia Trial (EMIAT) and the Canadian Amiodarone Myocardial
      Infarction Arrhythmia Trial (CAMIAT)--despite observing a 2-year mortality rate
      of about 15% as expected, could not demonstrate a significant reduction in
      mortality. Amiodarone decreases the risk of sudden death in postinfarction
      patients by about 35%. In patients with a history of heart failure and left
      ventricular dysfunction, evidence is not sufficiently strong to use amiodarone
      for prevention of sudden death. The 2 major trials on such patients, Group for
      the Study of Survival in Heart Failure in Argentina (Grupo de Estudio de la
      Sobrevida en la Insuficiencia Cardiaca en Argentina or GESICA) and the Survival
      Trial of Antiarrhythmic Therapy in Congestive Heart Failure (STAT-CHF), arrived
      at conflicting results. Meta-analyses have been performed to overcome the small
      sample size of these trials, with the aim of assessing the benefit of amiodarone
      on total mortality. Differences among the recruited populations make it difficult
      to extract clinically applicable conclusions from these overviews. Even accepting
      that amiodarone might decrease total mortality by 10%, it is difficult to
      identify the patients for whom such a beneficial effect applies. A practical
      consequence of amiodarone trials is that this drug can be used rather safely in
      patients with left ventricular dysfunction of any etiology as, in contrast to
      some class I agents, it does not increase mortality. Therefore, amiodarone is the
      drug of choice when antiarrhythmic drug treatment is indicated in patients with
      left ventricular dysfunction.

PMID- 10089842
TI  - Beta blockers: evidence versus wishful thinking.
AB  - Catecholamines and ischemia play an important role in the induction of
      ventricular tachyarrhythmias. Beta blockers antagonize the effect of
      catecholamines and have anti-ischemic properties. Several controlled studies
      performed in the early 1980s in patients after myocardial infarction have shown
      that beta-blocker therapy clearly decreases sudden and nonsudden cardiac death.
      Despite the lack of recent randomized trials, data from uncontrolled studies
      suggest that the beneficial effect of beta blockers is still present in the
      thrombolytic era. Thus, it is incomprehensible that today in the United States
      and in most parts of Europe, < 40% of post-myocardial infarction patients are
      treated with beta blockers. Even in patients with documented sustained
      ventricular tachycardias (VTs) or ventricular fibrillation (VF), clinical studies
      indicate that beta blockers improve survival. Thus, even in the thrombolytic era,
      beta blockers should be used as a basic therapy in patients who are at risk of
      sudden cardiac death.

PMID- 10089843
TI  - Secondary prevention of sudden death: the Dutch Study, the Antiarrhythmics Versus
      Implantable Defibrillator Trial, the Cardiac Arrest Study Hamburg, and the
      Canadian Implantable Defibrillator Study.
AB  - Although indisputably effective in the prevention of sudden death, use of
      implantable cardioverter defibrillator (ICD) therapy may not necessarily affect
      all-cause mortality, as most patients at risk also present with severely
      depressed left ventricular dysfunction. Correction of the sudden death risk in
      these patients creates a new clinical condition in need of a careful assessment.
      Should all-cause mortality be affected by the expected reduction in sudden death
      rate associated with ICD therapy, issues of critical importance, such as the time
      extent of life prolongation and the associated quality of life, still remain to
      established. To investigate the potential benefit of ICD therapy compared with
      antiarrhythmic drug treatment, 4 prospective studies--the Dutch trial, the
      Antiarrhythmics Versus Implantable Defibrillators (AVID) study, the Cardiac
      Arrest Study Hamburg (CASH), and the Canadian Implantable Defibrillator Study
      (CIDS)--have been conducted in which patients with documented sustained
      ventricular arrhythmia were randomized to 1 of these 2 treatment strategies. The
      enrollment criteria differed in these 4 studies: (1) in the Dutch trial, they
      included cardiac arrest secondary to a ventricular arrhythmia, old (> 4 weeks)
      myocardial infarction, and inducible ventricular arrhythmia; (2) in AVID and
      CIDS, ventricular fibrillation or poorly tolerated ventricular tachycardia; and
      (3) in CASH, cardiac arrest secondary to a ventricular arrhythmia regardless of
      the underlying disease. With regard to the antiarrhythmic drugs, the Dutch trial
      tested class I and III agents, whereas AVID and CIDS compared ICD therapy with
      class III agents (mostly amiodarone). In CASH, 3 drug subgroups were
      investigated: propafenone, amiodarone, and metoprolol. All trials used all-cause
      mortality as the primary endpoint. Data from these trials provide support for ICD
      as a therapy superior to antiarrhythmic drugs in prolonging survival in patients
      meeting the entry criteria. This review briefly summarizes the methods, results,
      limitations, and clinical implications of these 4 studies.

PMID- 10089844
TI  - The implantable cardioverter defibrillator and primary prevention of sudden
      death: the Multicenter Automatic Defibrillator Implantation Trial and the
      Coronary Artery Bypass Graft (CABG)-Patch Trial.
AB  - The Multicenter Automatic Defibrillator Implantation Trial (MADIT) and the
      Coronary Artery Bypass Graft (CABG)-Patch study were the first 2 randomized
      trials investigating the usefulness of the implanted cardioverter defibrillator
      (ICD) for primary prevention of sudden death. Patients enrolled in MADIT and CABG
      Patch had never experienced a sustained ventricular tachycardia (VT) but were
      thought to be at high risk of sudden death. All patients had coronary artery
      disease and severely suppressed left ventricular ejection fraction. CABG-Patch
      patients received their ICD during CABG surgery. Most MADIT patients already had
      received CABG or percutaneous transluminal coronary angiography and had no
      indication for revascularization procedures at study entry. MADIT patients had
      nonsustained spontaneous VT and inducible, nonsuppressible VT; CABG-Patch
      patients had only an abnormal signal-averaged electrocardiogram as an indicator
      of their arrhythmic risk. CABG-Patch patients did not benefit from ICD
      implantation, presumably due to the influence of revascularization on ischemia
      and left ventricular function. In contrast, MADIT patients showed an improved
      survival by the ICD. MADIT patients had no need for revascularization and,
      presumably, their risk indicator for arrhythmic events was stronger than the one
      used in CABG-Patch. MADIT criteria have become a class I indication for ICD
      implantation and, in the absence of testing for suppressibility of induced VTs, a
      class IIb criterion for ICD implantation. Screening for MADIT patients is
      expensive, as only relatively few patients after myocardial infarction fulfill
      the criteria. Nevertheless, in comparison with amiodarone, treatment of MADIT
      patients with ICDs seems to be cost-effective, especially if ICDs are implanted
      transvenously and have the improved battery longevity of the current devices.

PMID- 10089845
TI  - Impact of the Multicenter Automatic Defibrillator Implantation Trial on
      implantable cardioverter defibrillator indication trends.
AB  - Since publication of the Multicenter Automatic Defibrillator Implantation Trial
      (MADIT) in 1996, indications for implantation of implantable cardioverter
      defibrillators (ICDs) have expanded. Initial criticisms of the study have been
      addressed, including the need to await the conclusion of several additional ICD
      clinical trials. These other trials have generally shown an improved survival
      with ICD therapy when compared with antiarrhythmic agents. As a result, ICD
      implantation volumes have increased worldwide. However, ICD usage has regional
      variation with 120 implants per million population in the United States, 45 per
      million in Germany, but only 7 and 8 per million in France and the United
      Kingdom, respectively. Although many factors affect implant decisions,
      reimbursement issues are particularly important. Other factors may explain the
      slower growth in Europe when compared with the United States including greater
      skepticism regarding MADIT, less industry-sponsored marketing, and lack of
      unified cardiology society support for the MADIT recommendations. Nevertheless,
      it is anticipated that > 50,000 ICDs have been implanted worldwide in 1998, with
      a growing percentage in the countries of Europe.

PMID- 10089846
TI  - Antiarrhythmic drugs or implantable cardioverter defibrillators in heart failure:
      the "poor heart".
AB  - Ventricular tachycardia and ventricular fibrillation account for a substantial
      proportion of all deaths in patients with heart failure. Of currently available
      therapies, amiodarone and the implantable cardioverter defibrillator (ICD) appear
      to have the greatest potential to decrease sudden death in heart failure. In this
      article, the presently available information on the relative role of
      antiarrhythmic drugs, with a focus on amiodarone and ICDs in heart failure, is
      reviewed.

PMID- 10089847
TI  - The problem of out-of-hospital cardiac-arrest prevalence of sudden death in
      Europe today.
AB  - In Europe, 40% of all deaths of individuals who are 25-74 years of age are caused
      by cardiovascular disease. Cardiac disease is the underlying cause in two-thirds
      of out-of-hospital sudden deaths. The 28-day case fatality rate for the combined
      population of out-of-hospital coronary artery disease deaths and hospitalized
      acute myocardial infarction patients is approximately 50% in 29 of the regions
      included in the World Health Organization (WHO) Monitoring Trends and
      Determinants in Cardiovascular Disease registry. Of 14,065 patients included in
      the Swedish Cardiac Arrest Registry, resuscitation procedures were started in
      10,966 patients. The remaining 3,099 were considered definitely dead; 70% were
      witnessed, cardiac arrests and 32.3% had been given bystander cardiopulmonary
      resuscitation (CPR). The incidence of ventricular tachycardia (VT)/ventricular
      fibrillation (VF) in all patients was 43%, in witnessed cases 54%, and in
      nonwitnessed cases, 31%. The initial incidence of VT/VF was calculated to be
      approximately 60% in the whole population and 80-85% in those with probable
      cardiac disease. Survival to 1 month was 5.0% in the total population, 9.5% for
      those with VT/VF on the first electrocardiogram compared with 1.6% for those not
      in VT/VF. Survival rate was also calculated in relation to delay time to first
      defibrillation. Survival was 50% when defibrillation was performed immediately
      and decreased gradually to 0% for those with a delay time of 20 minutes. The
      survival rate after bystander CPR was 2.6-fold higher than the rate for those
      where no treatment was given until the ambulance arrived.

PMID- 10089848
TI  - New primary prevention trials of sudden cardiac death in patients with left
      ventricular dysfunction: SCD-HEFT and MADIT-II.
AB  - Primary prevention of sudden arrhythmic death in patients with organic heart
      disease with poor left ventricular function and/or heart failure is currently a
      major challenge in cardiology. Amiodarone (with or without beta blockers) and the
      implantable cardioverter defibrillator (ICD) are considered the 2 major
      therapeutic tools to prevent sudden arrhythmic death in these patients. Two large
      trials have been launched to define the prophylactic benefit of the ICD or
      amiodarone on total mortality in patients that receive optimal heart failure and
      anti-ischemic treatment but remain at high risk of dying suddenly. The Sudden
      Cardiac Death in Heart Failure Trial (SCD-Heft) is designed to determine whether
      amiodarone or the ICD will decrease overall mortality in patients with coronary
      artery disease or nonischemic cardiomyopathy who are in heart failure New York
      Heart Association (NYHA) class II or III and have a left ventricular ejection
      fraction < 35%. The primary endpoint is total mortality; secondary objectives are
      comparison of arrhythmic and nonarrhythmic mortality and morbidity in the 3 arms
      as well as quality of life, cost-effectiveness, and incidence of episodes of
      ventricular tachyarrhythmias. The Multicenter Automatic Defibrillator
      Implantation Trial (MADIT) II is a follow-up study to the MADIT trial. It
      examines the prophylactic benefit in coronary artery disease patients with a left
      ventricular ejection fraction of < 30%, who have had at least 1 myocardial
      infarction but require no further risk stratification. MADIT II is a sequential
      design trial that compares ICD versus no ICD therapy. Programmed electrical
      stimulation to test inducibility of ventricular tachycardia is performed during
      ICD implantation, and various noninvasive risk markers are tested after
      randomization. Primary endpoint is total mortality, and secondary objectives are
      quality-of-life issues as well as cost-effectiveness ratio.

PMID- 10089849
TI  - Use of the prophylactic implantable cardioverter defibrillator for patients with
      normal hearts.
AB  - About 10-20% of patients dying suddenly and unexpectedly do not have structural
      heart disease. The major causes of sudden death in this population are acute
      ischemia, the syndrome of right bundle branch block, and ST-elevation from V1 to
      V3, the long QT-syndrome, and the Wolff-Parkinson-While syndrome. In some
      patients, none of these syndromes can be recognized and ventricular fibrillation
      is classified as idiopathic. There are good preventive and therapeutic methods
      against acute ischemia and there are also curative treatments for the Wolff
      Parkinson-White syndrome. Patients with idiopathic ventricular fibrillation
      cannot be recognized beforehand. However, there are electrocardiographic and
      genetic markers for the Brugada syndrome and the long QT syndrome. It is,
      therefore, justified to discuss the possible role of the prophylactic
      defibrillator to prevent sudden death in these 2 syndromes for which no effective
      treatment exists. Patients with Brugada syndrome have a high incidence of sudden
      death, and prophylactic defibrillators are indicated in patients with inducible
      arrhythmias at electrophysiologic study, irrespective of symptoms. On the
      contrary, the incidence of sudden death in the long QT syndrome is very low,
      making prophylactic defibrillator implantation not cost-effective.

PMID- 10089850
TI  - What risk should justify implantable cardioverter defibrillator therapy?
AB  - Implantable cardioverter defibrillators (ICDs) were developed to prevent sudden
      cardiac death in patients with ventricular tachycardia (VT) or ventricular
      fibrillation (VF). Their safety and efficacy have been proved in multiple
      retrospective and prospective studies. Many of the published trials were directed
      at secondary prevention for patients who had already had a sudden cardiac death
      or a sustained VT. For primary prevention, the information available is limited,
      as only 2 trials have yet been published. Ongoing trials will probably allow us
      to broaden the indications for prophylactic ICD implantation. Justification of
      the risk will have to be evaluated against complexity of the implant, the latter
      including not only cost but quality of life and morbidity associated with an ICD.
      However, our efforts still have to be directed to improve risk stratification and
      to decrease the complexity of the procedure.

PMID- 10089851
TI  - Which strategy is "best" after myocardial infarction? The Beta-blocker Strategy
      plus Implantable Cardioverter Defibrillator Trial: rationale and study design.
AB  - The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator (BEST-ICD)
      Trial is a multicenter prospective randomized trial that started in June 1998, in
      95 centers in Italy and Germany. The trial will test the hypothesis whether, in
      high-risk post myocardial infarction (MI) patients already treated with beta
      blockers, electrophysiologic study (EPS)-guided therapy (including the
      prophylactic implantation of implantable cardioverter defibrillator [ICD] in
      inducible patients) will improve survival compared with conventional therapy.
      Patients eligible for the study are survivors of recent MI (> or = 5 and < or =
      21 days), aged < or = 80 years, with left ventricular ejection fraction < or =
      35% and > or = 1 of the following additional risk factors: (1) ventricular
      premature beats > or = 10/hour; (2) decreased heart rate variability (standard
      deviation of unusual RR intervals < 70 msec); and (3) presence of ventricular
      late potentials. Furthermore, all enrolled patients must be able to tolerate at
      least 25 mg of metoprolol per day. These patients constitute about 9% of all
      patients with recent MI and are expected to have a 2-year all-cause mortality >
      25% of which 50% is anticipated to be from sudden death. The main criteria of
      exclusion from the study are (1) a history of sustained ventricular arrhythmia;
      (2) documentation of nonsustained ventricular tachycardia during the screening
      phase; and (3) the need for myocardial revascularization and contraindications or
      intolerance to beta-blocker therapy. Eligible patients will be randomized to 2
      different therapeutic strategies: conventional strategy or EPS/ICD strategy.
      Patients allocated to the EPS/ICD strategy will undergo further risk
      stratification, and electrophysiologically inducible patients (approximately 35%)
      will receive prophylactic ICDs, in addition to the conventional therapy, whereas
      noninducible patients will be only conventionally treated. The primary endpoint
      of the study will be death from all causes. By hypothesizing a 30% reduction in
      the 2-year mortality (from 20% to 14%) in the EPS/ICD group compared with
      conventionally treated patients, 1,200 patients will have to be included. A
      triangular, 2-sided sequential design with preset boundaries, for a 5%
      significance level and 90% power to detect a reduction in 2-year mortality from
      20% to 14%, will be used to permit early termination of the trial if the strategy
      is found to be efficacious, no difference, or inefficacious.

PMID- 10089852
TI  - Has the survival of the heart failure population changed? Lessons from trials.
AB  - Heart failure is a common and growing problem with a poor prognosis both in terms
      of morbidity and mortality. Furthermore, the natural history of heart failure can
      be modified dramatically by appropriate therapy. The purposes of this article are
      to (1) describe briefly the epidemiology and current therapy of heart failure;
      (2) examine potential differences between heart failure as studied in the
      clinical trials, compared with heart failure in the community; and (3) suggest a
      number of areas where improvements might be made or further research is required.

PMID- 10089853
TI  - Biventricular pacing in patients with congestive heart failure: two prospective
      randomized trials. The VIGOR CHF and VENTAK CHF Investigators.
AB  - Epidemiologic studies suggest that 20-30% of patients diagnosed with symptomatic
      congestive heart failure (CHF) have intraventricular conduction disorders
      characterized by a discoordinate contraction pattern and wide QRS. Biventricular
      pacing is an emerging therapy allowing simultaneous electrical stimulation of the
      right and left ventricles with the use of an implantable pacing system. The aim
      of this article is to describe 2 prospective randomized multicenter trials
      examining the effects of biventricular pacing on functional capacity, quality of
      life, and hemodynamic status in patients with dilated cardiomyopathy and
      intraventricular delay. The VIGOR CHF Trial is designed to assess functional and
      symptomatic improvement in heart failure patients with biventricular pacing and
      without a concomitant indication for conventional bradycardia pacemaker therapy.
      To assess for potential placebo effects, patients are randomized to receive
      either biventricular pacemaker therapy or no pacing therapy for the first 6
      weeks, after which both groups receive pacing therapy. The VENTAK CHF trial uses
      an implantable cardioverter defibrillator system (ICD) designed to provide
      chronic biventricular pacing therapy in addition to treating ventricular
      tachyarrhythmias. All patients receive conventional ICD and CHF therapy
      throughout the study and are randomized in a 2-period crossover design to receive
      either no pacing or biventricular pacing for 3-month intervals. Patient
      enrollment in both studies is ongoing, with a closed analysis. The unique designs
      of these trials provide the opportunity to study this therapy in high-risk
      patients who have been optimally treated for heart failure.

PMID- 10089854
TI  - Can right-sided atrioventricular sequential pacing provide benefit for selected
      patients with severe congestive heart failure?
AB  - This study reports on the methods and results of applying right-sided
      atrioventricular (AV) pacing in 26 patients with advanced cardiomyopathy. Ten of
      these patients had ischemic cardiomyopathy. Of the 16 patients with nonischemic
      cardiomyopathy, 10 were idiopathic and 6 were due to secondary causes. The
      patients had a mean age of 56 +/- 12 years and a left ventricular ejection
      fraction of 26 +/- 11%. Two transvenous stimulation electrodes were temporarily
      placed in the high right atrium and right ventricle, respectively. A Swan Ganz
      catheter was positioned into the pulmonary artery to determine cardiac output by
      the thermodilution method and to measure the pressure in the pulmonary artery and
      right atrium. In addition, aortic pressure was measured through a catheter sheath
      via the right femoral artery. Systemic and pulmonary vascular resistance were
      calculated. Stimulation was performed in VVI and DDD pacing modes using different
      AV intervals (40, 80, 125, 150, 175, 200, and 250 msec). No increase of cardiac
      output was observed for the overall study cohort (p = 0.51). At VVI pacing,
      stroke volume significantly decreased from 66 +/- 20 mL to 53 +/- 13 mL (p <
      0.01). We distinguished between responders who developed an increase of cardiac
      output of > 1 L/min (n = 12, 46%) and nonresponders (n = 14, 54%). Etiology of
      either ischemic or nonischemic cardiomyopathy for responders, as well as
      conduction disturbances (first-degree AV block, LBBB, RBBB), were equally
      distributed among both groups. Using an AV delay of 150 and 175 msec, responders
      to DDD pacing derived a significant increase in cardiac output. An AV delay of
      150 msec produced both a significant increase of stroke volume and decrease of
      systemic vascular resistance. In 46% of patients with dilated cardiomyopathy of
      either ischemic or nonischemic origin, right-sided AV-sequential pacing brought
      about an improvement of left ventricular function in terms of enhanced cardiac
      output. We suggest individual testing in all patients with severe left
      ventricular dysfunction to find responders.

PMID- 10089855
TI  - The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale,
      design, and endpoints of a prospective randomized multicenter study.
AB  - In conjunction with pharmacologic therapy, pacing has been proposed as a
      potential treatment to decrease symptoms in patients with moderate-to-severe
      congestive heart failure (CHF). Uncontrolled studies of pacing therapy for CHF
      dealing with different pacing sites, modes of pacing, and atrioventricular delays
      have reported mixed outcomes. The Pacing Therapies in Congestive Heart Failure
      (PATH-CHF) study is a single-blind, randomized, crossover, controlled trial
      designed to evaluate the effects of pacing on acute hemodynamic function and to
      assess chronic clinical benefit in patients with moderate-to-severe CHF. The
      effect of pacing on oxygen consumption at peak exercise and at anaerobic
      threshold during cardiopulmonary exercise tests, and on 6-minute walk distance,
      have been selected as primary endpoints of the study. Secondary endpoints of the
      trial were changes in New York Heart Association (NYHA) functional class, quality
      of-life as assessed by the Minnesota Living with Heart Failure questionnaire, and
      hospitalization frequency. Finally, changes in ejection fraction, cardiac output,
      and filling pattern were assessed by echocardiography. The trial was planned to
      include 53 patients from 7 centers in Europe over a period of 3 years. The study
      was divided into 2 parts: acute testing and chronic follow-up. The acute study,
      performed during the pacemaker implantation, involved extensive testing using a
      custom-designed computer (FLEXSTIM) and a unique burst pacing protocol (FLEXSTIM
      protocol) to determine the best ventricular pacing sites and the most appropriate
      atrioventricular delays. The chronic phase consisted of a crossover study
      designed to test in each patient the best univentricular pacing site and
      biventricular pacing as assessed by the acute hemodynamic study. The study
      started with the first implant in 1995 and has, to date, included 42 patients.
      The study is expected to be completed by the end of 1998. The results of a first
      interim analysis showed trends toward improvement in all primary and secondary
      endpoints during the pacing periods compared with no pacing.

PMID- 10089856
TI  - Transvenous biventricular pacing for heart failure: can the obstacles be
      overcome?
AB  - Despite increasing evidence of hemodynamic benefit and long-term improvement in
      clinical status of congestive heart failure (CHF) patients with left ventricular
      and biventricular pacing, the risks and technical limitations of placing a
      permanent left ventricular pacing lead have prevented widespread clinical
      adoption of this therapy. Results of this and other recent investigations suggest
      it is necessary to target specific sites on the left ventricle to maximize
      hemodynamic benefit. However, limitations and variations of coronary vein
      anatomy, as well as patient safety, lead dislodgement, pacing thresholds, lead
      handling, and ease-of-use issues, present technical challenges for current
      transvenous permanent pacing lead designs. However, a new transvenous lead system
      based on an over-the-wire design appears to solve many of these problems and has
      proved feasible in acute clinical studies.

PMID- 10089857
TI  - Potential benefit of biventricular pacing in patients with congestive heart
      failure and ventricular tachyarrhythmia.
AB  - Treatment of congestive heart failure (CHF) aims for symptomatic relief and
      reduction of mortality both from sudden death and pump failure. The implantable
      cardioverter defibrillator (ICD) is highly effective in the prevention of sudden
      death, but no mortality benefit in advanced CHF has yet been shown. Biventricular
      pacing may lead to functional improvement in selected patients with CHF. Thus, a
      biventricular pacemaker with defibrillation capabilities may be ideal for
      patients with advanced CHF. We retrospectively analyzed the data from 384
      patients (age 59 +/- 12 years, 322 male and 62 female) with regard to New York
      Heart Association (NYHA) CHF class, mean QRS duration, mean PR interval, presence
      of a QRS > 120 msec and incidence of atrial fibrillation at the time of ICD
      implantation. Based on eligibility criteria from studies in biventricular pacing,
      we analyzed how many patients may benefit from biventricular pacing. Patients
      with CHF were older (NYHA class III: 60.9 +/- 9.7, class II: 61.3 +/- 10 versus
      class I: 50.8 +/- 13.6 years, p < 0.001 each) and mean QRS duration was longer
      with advanced CHF (NYHA class III 127.8 +/- 30 msec; class II 119.4 +/- 27.7
      msec; class 0-1: 103.9 +/- 17.7 msec, p < 0.001, analysis of variance) as was the
      mean PR interval (NYHA class III 189.9 +/- 33.5 msec; class II 176.1 +/- 29.3
      msec; class 0-1 162.7 +/- 45.9 msec, p < 0.001, analysis of variance). The
      incidence of atrial fibrillation was higher in class III (25.5%) compared with
      class 0-1 (16.9%) and class II patients (14.1%, p = 0.043, chi-square test). A
      total of 28 patients (7.3%) fulfilled eligibility criteria for biventricular
      pacing if NYHA class III patients were considered candidates and 48 (12.5%) if
      patients with NYHA II CHF and ejection fraction < or = 30% were included. Thus,
      biventricular pacing may offer a promising therapeutic approach for a significant
      proportion of patients with CHF at risk for ventricular tachyarrhythmia.

PMID- 10089858
TI  - The implantable cardioverter defibrillator as a "bridge to transplant": a viable
      clinical strategy?
AB  - Heart transplantation is an accepted therapeutic option for patients with end
      stage heart disease. However, because the availability of heart donors fails to
      keep pace with the growing demand, increasing numbers of potential recipients are
      placed on the waiting list, resulting in longer waiting times. About 20% of
      patients die while awaiting heart transplantation. The majority die from
      progressive pump failure (46%), whereas about 30% of all deaths occur suddenly.
      Monitored terminal cardiac electrical activity in patients dying while awaiting
      transplantation reveals that bradyarrhythmias and/or electromechanical
      dissociation are involved in 68% of cases and ventricular tachyarrhythmias in 32%
      of cases. Patients with a history of aborted cardiac arrest are at highest risk
      for recurrent malignant arrhythmias. The implantable cardioverter defibrillator
      (ICD) is the most effective therapy for preventing sudden cardiac death from
      ventricular tachyarrhythmias. Pooled data from a total of 75 sudden death
      survivors listed for cardiac transplantation demonstrate that ICD therapy can be
      applied with low mortality, low morbidity, and high efficacy, with up to 94% of
      the patients receiving appropriate shocks during the waiting period. However,
      there is considerable concern that this early survival benefit conferred by the
      ICD may be nullified by the competing risk of death due to terminal pump failure,
      as the waiting list and waiting time to transplantation lengthens. In advanced
      heart failure, risk stratification for sudden tachyarrhythmic death is only of
      limited value. Therefore, although sudden tachyarrhythmic death appears to
      constitute only a minor fraction of total cardiac death in patients awaiting
      heart transplantation, prophylactic ICD implantation as on electronic bridge to
      transplant may be considered. To define conclusively the role of prophylactic ICD
      therapy in this setting, prospective randomized studies are needed.

PMID- 10089859
TI  - Combining nonpharmacologic therapies for advanced heart failure: the Munster
      experience with the assist device-defibrillator combination.
AB  - Implantable cardioverter defibrillators (ICDs) and ventricular assist devices
      (VADs) have been used as a bridge to cardiac transplantation. In selected
      patients, the combined implantation may be required. This study was motivated by
      a case of a 33-year-old female patient with giant cell myocarditis who died of
      ventricular tachyarrhythmias after having been placed on a VAD with which she had
      been treated on an out-of-hospital basis for a prolonged period of time. A
      subsequent retrospective analysis of our data showed that, of 73 patients who had
      to be bridged mechanically (54 Novacor, 12 TCI Heartmate, 4 Thoratec, 3 Medos) in
      our institution between 1993 and 1998, 10 patients had undergone defibrillator
      implantation either before (n = 8) or after (n = 2) implantation of a VAD. The
      cases are presented, and the feasibility of the combination therapy discussed.

PMID- 10089860
TI  - Evolving indications for permanent pacing.
AB  - Indications for permanent pacemakers have expanded in recent years. The American
      College of Cardiology (ACC) and American Heart Association (AHA) guidelines for
      implantation of cardiac pacemakers were recently updated and now include several
      of the newer indications. Greatest interest about newer applications of pacemaker
      therapy focuses on hypertrophic obstructive cardiomyopathy, dilated
      cardiomyopathy, and pacing for the prevention of atrial fibrillation. Pacing for
      neurocardiogenic syncope remains controversial despite emerging data. Pacing for
      long QT syndrome, pacing after cardiac transplantation, and pacing for
      hemodynamic improvement in the occasional patient with first-degree
      atrioventricular block and hemodynamic compromise also warrant attention.
      Available clinical data are discussed in the context of the recent ACC and AHA
      guidelines.

PMID- 10089861
TI  - Clinical significance of multiple sensor options: rate response optimization,
      sensor blending, and trending.
AB  - The gold standard for rate modulation is the sinus node. To improve the rate
      modulation provided by artificial sensors, new sensors have to be developed or 2
      different sensor systems can be combined within a single device. Association
      combination of a sensor with a rapid-response fast-rate increase sensor
      (activity) and a progressive, more specific sensor (QT ventilation) is generally
      used. Sensor combinations require adequate sensor blending for signal production
      and prioritization during rate modulation. However, in the new devices, some
      other aspects of rate modulation could be taken into consideration, particularly
      circadian rate variations to obtain lower rates at nighttime than during daytime,
      and automatic adaptation of the slope of rate increase during exercise, according
      to the patient's fitness, heart function, age, etc. Despite the need for
      automaticity, manual programming could continue to be useful to adapt rate
      modulation with data from sensor trending memories.

PMID- 10089862
TI  - Taking advantage of sophisticated pacemaker diagnostics.
AB  - The ever-increasing complexity of pacing systems, combined with functions that
      vary from one manufacturer to another, can pose challenges during analysis of
      device function. Standard pacemaker diagnostics are measured data, electrogram
      telemetry, maker annotations and event counters, albeit with their current
      limitations. New diagnostic features discussed include time-based diagnostics,
      histograms of sensed amplitudes, pacing thresholds, or impedance trending. Mode
      switching algorithms, combined with diagnostic features, facilitate the use of
      dual-chamber devices in patients with paroxysmal atrial tachyarrhythmias. The
      introduction of electrogram storage into pacemakers further improves diagnostic
      capabilities and allows a permanent validation and optimization of diagnostic and
      therapeutic algorithms. External diagnostic devices, which provide Holter
      recordings with continuous marker annotations and patient-triggered diagnostics,
      are additional features that will become increasingly important.

PMID- 10089863
TI  - How smart should pacemakers Be?
AB  - The concept of the "smart" pacemaker has been continuously changing during 40
      years of progress in technology. When we talk today about smart pacemakers, it
      means optimal treatment, diagnosis, and follow-up for patients fitting the
      current indications for pacemakers. So what is smart today becomes accepted as
      "state of the art" tomorrow. Originally, implantable pacemakers were developed to
      save lives from prolonged episodes of bradycardia and/or complete heart block.
      Now, in addition, they improve quality of life via numerous different functions
      acting under specific conditions, thanks to the introduction of microprocessors.
      The devices have become smaller, with the miniaturization of the electrical
      components, without compromising longevity. Nevertheless, there are still some
      unmatched objectives for these devices, for example, the optimization of cardiac
      output and the management of atrial arrhythmias in dual-chamber devices.
      Furthermore, indications continue to evolve, which in turn require new,
      additional functions. These functions are often very complex, necessitating
      computerized programming to simplify application. In addition, the follow-up of
      these devices is time-consuming, as appropriate system performance has to be
      regularly monitored. A great many of these functions could be automatically
      performed and documented, thus enabling physicians and paramedical staff to avoid
      losing time with routine control procedures. In addition, modern pacemakers offer
      extensive diagnostic functions to help diagnose patient symptoms and pacemaker
      system problems. Different types of data are available, and their presentation
      differs from one company to the other. This huge amount of data can only be
      managed with automatic diagnostic functions. Thus, the smart pacemaker of the
      near future should offer high flexibility to permit easy programming of available
      therapies and follow-up, and extensive, easily comprehensible diagnostic
      functions.

PMID- 10089864
TI  - Pacemaker leads: performance and progress.
AB  - Pacing leads remain the "weaker link" of the permanent pacing system. Lead
      failure has been an issue since the beginning of implantable pacemaker therapy.
      Modern electronics have brought about considerable progress in pacing technology,
      but lead design has been slower to evolve and problems persist. IS-1
      standardization must be considered a significant advance, but some issues
      regarding IS-1 standardization persist and have been the cause of some
      compatibility problems. With respect to lead insulation, silicone has proved to
      offer total reliability for > 30 years. In the search for better handling
      characteristics, polyurethane 80A was employed for bipolar leads, but it failed
      to demonstrate satisfactory insulating properties. New insulation materials, such
      as ethylene-fluoro-ethylene (ETFE), and coated wire technology look promising,
      having shown 99.32% survival at 5-year follow-up. Reliability is the main
      objective in lead design, but leads should provide low battery consumption as
      well. Low coil resistance, with high electrode impedance in steroid-eluting
      leads, is the standard at present. Low polarization is a desirable property for 2
      main reasons: (1) in conjunction with low-threshold leads, it decreases battery
      consumption; and (2) it allows capture detection and, therefore, safer pacing at
      low battery consumption. Lead tip design as well as pacing pulse configuration
      can influence polarization.

PMID- 10089865
TI  - Future of bradyarrhythmia therapy systems: automaticity.
AB  - Since the first fixed-rate ventricular pacemaker was introduced in the late
      1950s, pacing systems have evolved rapidly. Current developments focus on making
      devices more sophisticated and less complex--a challenging combination.
      Automaticity features such as beat-by-beat capture verification, sensitivity
      threshold adaptation, and algorithms to govern dynamically the maximum sensor
      rate have either recently been introduced or are likely to be introduced in the
      near future. Technologic advances are likely to allow meaningful improvements in
      current drain, battery performance, memory capacity, signal processing,
      telemetry, and programmer interface. Bradyarrhythmia therapy devices of the
      future promise to go beyond the pacemaker. Ultimately, pacing systems will become
      part of integrated cardiac rhythm management systems.

PMID- 10089866
TI  - Mode switching for atrial tachyarrhythmias.
AB  - Mode switching for atrial tachyarrhythmias is a concept that originated from use
      of DDI mode and was introduced in the early 1990s to prevent dual-chamber
      pacemakers from ventricular tracking of rapid atrial rates. This article
      describes the currently available systems and discusses the advantages and
      disadvantages of the technique. The results of a preliminary randomized
      controlled trial of 1 algorithm and plans for a second study are presented.

PMID- 10089867
TI  - Effect of pacing mode on morbidity and mortality: update of clinical pacing
      trials.
AB  - Retrospective studies have suggested that, in patients with sick sinus syndrome,
      it has been recognized that atrial, dual-chamber, or other so-called physiologic
      modes of pacing are associated with a lower incidence of atrial fibrillation,
      stroke, heart failure, and death than is single-chamber ventricular pacing.
      Retrospective data in patients with atrioventricular block are less robust, but
      still suggest lower mortality and morbidity with dual-chamber pacing compared
      with ventricular pacing alone. Overall, the reduction in risk of atrial
      fibrillation with dual-chamber compared with ventricular pacing has been
      calculated at 62%, and for death 36%. Retrospective studies are, of course,
      potentially subject to bias, and there may be a tendency to implant cheaper,
      simpler pacemakers in older, sicker patients, which could explain the apparent
      difference in outcome. Prospective studies are, therefore, required; results from
      3 such studies, in which pacing mode was randomly allocated, have been recently
      published. These, in general, support the apparent benefit of dual-chamber pacing
      in patients with sick sinus syndrome, but give equivocal results in patients with
      heart block. Other trials are in progress, and their results are awaited. Like
      all good trials, they will, in addition to providing some answers, generate
      further questions. They should provide the evidence on which cost-effective
      pacing policies may be based.

PMID- 10089868
TI  - Managing atrial tachyarrhythmias in patients with implantable cardioverter
      defibrillators.
AB  - The implantable cardioverter defibrillator (ICD) is accepted as the therapy of
      choice in preventing sudden cardiac death. Multiple studies, such as
      Antiarrhythmics Versus Implantable Defibrillators (AVID), the Canadian
      Implantable Defibrillator Study (CIDS), the Cardiac Arrest Study Hamburg (CASH),
      and the Multicenter Automatic Defibrillator Implantation Trial (MADIT), have
      shown a substantial benefit in survival rates for patients treated with ICDs
      compared with antiarrhythmic drug treatment. The detection of spontaneous
      ventricular tachycardias (VT) is based primarily on the programmed heart rate for
      intervention of the device. Supraventricular tachycardias (SVTs) cause
      unnecessary therapy delivery in about 10-20% of patients with ICDs. ICD therapy
      needs to be improved to become more specific for VT detection, by implementing
      algorithms that discriminate between VTs and SVTs. The enhanced detection
      criteria in currently available ICD devices are able to decrease the rate of
      unnecessary therapy to < 5% of patients. Atrial tachyarrhythmias can be managed
      with programmable features of the device, antiarrhythmic drug treatment, and in
      rare cases, ablation procedures. Dual-chamber ICDs, requiring an additional
      atrial lead, are indicated in specific situations of slow VT and concurrent,
      continuous SVTs at very similar heart rates. Using all these options, SVTs can be
      managed to achieve an acceptably low incidence of unnecessary therapy delivery in
      < 5% of ICD patients.

PMID- 10089869
TI  - The atrial defibrillator: a stand-alone device or part of a combined dual-chamber
      system?
AB  - Atrial fibrillation (AF) is an extremely common arrhythmia seen in clinical
      practice. Because of the limited efficacy of traditional therapeutic strategies
      to restore and maintain normal sinus rhythm, several nonpharmacologic options
      have evolved. The promising results achieved with internal atrial defibrillation
      have facilitated the development of an implantable atrial defibrilator.
      Preliminary results obtained from an initial study on a small number of highly
      selected patients with refractory AF suggest that atrial defibrillation can be
      performed effectively and safely with adequate patient tolerance by using a stand
      alone device. The extension of this therapy will depend on the results of well
      designed prospective studies comparing this new therapeutic option with
      traditional methods. Several acute studies have shown that internal conversion of
      AF is feasible at low energies with current endocardial transvenous lead
      configurations primarily designed for ventricular defibrillation, but long-term
      efficacy has, to date, only been demonstrated with atrial implantable
      defibrillator lead systems. As AF is a frequent arrhythmia in implantable
      cardioverter defibrillator (ICD) recipients, it would seem desirable to
      incorporate the capability for atrial defibrillation into an ICD. Clinical
      studies have shown that an atrial defibrillator, as part of a combined dual
      chamber ICD system, may not require a potentially complicated switching network
      for establishing different electrode configurations for atrial and ventricular
      tachyarrhythmia. The efficacy in atrial cardioversion of such a combined, less
      complex device seems to be as high as reported for a pure atrial defibrillator,
      but generally at somewhat higher energy requirements. The results of further
      investigations will show whether a dual-chamber cardioverter defibrillator would
      be of clinical relevance in patients with ventricular and supraventricular
      tachyarrhythmia.

PMID- 10089870
TI  - A new system for catheter ablation of atrial fibrillation.
AB  - Increased attention is now being focused on developing new technologies to cure
      atrial fibrillation using catheter ablation techniques. The performance of a MAZE
      type procedure using standard catheter ablation technologies is arduous and is
      associated with an unacceptable risk of complications. The Guidant Heart Rhythm
      Technologies Linear Ablation System was developed to create long transmural
      linear lesions. Unique features of this system include the availability of
      different preshaped multi-electrode steerable ablation catheters, the use of
      phased radiofrequency (RF) energy, and the control of RF output by varying the
      duty cycle. A prospective multicenter clinical trial to evaluate the safety and
      efficacy of a right atrial ablation procedure using this technology to treat
      atrial fibrillation is currently underway. To date, 15 patients have been
      enrolled and the procedure was acutely effective in 14 of 15 patients with no
      complications. Atrial fibrillation has recurred during short-term follow-up in 12
      of 15 patients, a not surprising result, because this initial phase of testing
      involved only right-sided ablation. The early results of the phase I clinical
      trial confirm the findings of others that successful ablation of chronic atrial
      fibrillation is likely to require a left atrial approach. This clinical trial, as
      well as others that are currently underway, will be invaluable in the continuing
      development of catheter ablation of atrial fibrillation and, ultimately, in
      determining if the routine use of this therapeutic tool can become a reality.

PMID- 10089871
TI  - Multisite or alternate site pacing for the prevention of atrial fibrillation.
AB  - The role of permanent pacing in preventing atrial fibrillation in patients at
      risk for this arrhythmia is a relatively new concept. Existing retrospective
      studies support the superiority of atrial-based pacing over ventricular
      stimulation with respect to lowering the incidence of atrial fibrillation.
      Constant rate overdrive pacing has been shown to reverse abnormalities in
      conduction or refractoriness that are dependent on bradycardia and suppress
      atrial ectopic complexes. Multisite (biatrial and dual right atrial) pacing is a
      promising concept. The antiarrhythmic mechanism is not well understood, but
      atrial resynchronization and reduction of site-dependent conduction delay of
      atrial premature complexes may be relevant. The cardiology community awaits
      additional data from prospective trials that are currently underway.

PMID- 10089872
TI  - Atrioventricular nodal ablation and pacemaker implantation in patients with
      atrial fibrillation.
AB  - In drug-resistant, poorly tolerated atrial fibrillation, atrioventricular (AV)
      junction catheter ablation can be proposed as the last-resort option.
      Technically, the procedure is easy to perform and relatively safe. Interruption
      of the AV conduction implies the insertion of a permanent pacemaker. In patients
      with chronic atrial fibrillation, a VVIR pacemaker is inserted. For those having
      severely symptomatic episodes of paroxysmal atrial fibrillation, DDDR mode
      switching devices are more appropriate. Results are remarkable. The treatment is
      highly effective in controlling symptoms and improving general well-being.
      Exercise capacity is also increased. Left ventricular ejection fraction may
      increase after ablation, an effect that is mainly apparent in patients with
      markedly depressed myocardial function. Consumption of healthcare resources has
      been shown to decrease significantly in the aftermath of AV junction ablation.
      However, sudden-death risk has been invoked as a limiting factor for the
      procedure. This may be due to AV-block-related ventricular tachyarrhythmias,
      occurring early after ablation, whereas the reasons for late sudden deaths are
      somewhat more obscure. It is unclear whether such events are procedure-related or
      rather secondary to the underlying heart disease. Thus, AV junction ablation for
      refractory atrial fibrillation remains the only nonpharmacologic, alternative
      therapy that is performed on a routine basis. Failure of newer therapeutic
      approaches should further reinforce the clinical impact of this procedure in the
      future.

PMID- 10089873
TI  - Flipping the switch to an active spliceosome.

PMID- 10089874
TI  - Waves of malarial var-iations.

PMID- 10089875
TI  - Cystic fibrosis and the salt controversy.

PMID- 10089876
TI  - Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and
      NF-AT.

PMID- 10089877
TI  - Solution structure of BID, an intracellular amplifier of apoptotic signaling.
AB  - We report the solution structure of BID, an intracellular cross-talk agent that
      can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after
      Caspase 8 cleavage. BID contains eight alpha helices where two central
      hydrophobic helices are surrounded by six amphipathic ones. The fold resembles
      poreforming bacterial toxins and shows similarity to BCL-XL although sequence
      homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we
      modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the
      known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of
      BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3
      domain-dependent and -independent modes of action in inducing mitochondrial
      damage.

PMID- 10089878
TI  - Solution structure of the proapoptotic molecule BID: a structural basis for
      apoptotic agonists and antagonists.
AB  - Members of the BCL2 family of proteins are key regulators of programmed cell
      death, acting either as apoptotic agonists or antagonists. Here we describe the
      solution structure of BID, presenting the structure of a proapoptotic BCL2 family
      member. An analysis of sequence/structure of BCL2 family members allows us to
      define a structural superfamily, which has implications for general mechanisms
      for regulating proapoptotic activity. It appears two criteria must be met for
      proapoptotic function within the BCL2 family: targeting of molecules to
      intracellular membranes, and exposure of the BH3 death domain. BID's activity is
      regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and
      significantly changing the surface charge and hydrophobicity, resulting in a
      change of cellular localization.

PMID- 10089879
TI  - A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly.
AB  - Proteins modified by multiubiquitin chains are the preferred substrates of the
      proteasome. Ubiquitination involves a ubiquitin-activating enzyme, E1, a
      ubiquitin-conjugating enzyme, E2, and often a substrate-specific ubiquitin
      protein ligase, E3. Here we show that efficient multiubiquitination needed for
      proteasomal targeting of a model substrate requires an additional conjugation
      factor, named E4. This protein, previously known as UFD2 in yeast, binds to the
      ubiquitin moieties of preformed conjugates and catalyzes ubiquitin chain assembly
      in conjunction with E1, E2, and E3. Intriguingly, E4 defines a novel protein
      family that includes two human members and the regulatory protein NOSA from
      Dictyostelium required for fruiting body development. In yeast, E4 activity is
      linked to cell survival under stress conditions, indicating that eukaryotes
      utilize E4-dependent proteolysis pathways for multiple cellular functions.

PMID- 10089880
TI  - Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of
      novel polyubiquitin chains for DNA repair.
AB  - Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin
      conjugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS2
      encoded UEV protein has been genetically implicated in error-free postreplicative
      DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific
      heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p
      dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13
      yeast strain is UV sensitive, and single, double, and triple mutants of the
      UBC13, MMS2, and ubiquitin (ubiK63R) genes display a comparable phenotype. These
      findings support a model in which an Mms2p/Ubc13p complex assembles novel
      polyubiquitin chains for signaling in DNA repair, and they suggest that UEV
      proteins may act to increase diversity and selectivity in ubiquitin conjugation.

PMID- 10089881
TI  - Sprouty, an intracellular inhibitor of Ras signaling.
AB  - Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF
      receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty-
      eyes have excess photoreceptors, cone cells, and pigment cells. Sprouty's
      function is, however, more widespread. We show that it also interacts genetically
      with the receptor tyrosine kinases Torso and Sevenless, and it was first
      discovered through its effect on FGF receptor signaling. In contrast to an
      earlier proposal that Sprouty is extracellular, we show by biochemical analysis
      that Sprouty is an intracellular protein, associated with the inner surface of
      the plasma membrane. Sprouty binds to two intracellular components of the Ras
      pathway, Drk and Gap1. Our results indicate that Sprouty is a widespread
      inhibitor of Ras pathway signal transduction.

PMID- 10089882
TI  - Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry.
AB  - Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors
      serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV
      1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors
      contains an N-terminal region that is acidic and tyrosine rich. Here, we show
      that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is
      posttranslationally modified by O-linked glycosylation and by sulfation of its N
      terminal tyrosines. Sulfated tyrosines contribute to the binding of CCR5 to MIP-1
      alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to
      enter cells expressing CCR5 and CD4. CXCR4, another important HIV-1 coreceptor,
      is also sulfated. Tyrosine sulfation may contribute to the natural function of
      many 7TMS receptors and may be a modification common to primate immunodeficiency
      virus coreceptors.

PMID- 10089883
TI  - EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin,
      influencing clathrin redistribution and EGF uptake.
AB  - Epidermal growth factor (EGF) binding to its receptor causes rapid
      phosphorylation of the clathrin heavy chain at tyrosine 1477, which lies in a
      domain controlling clathrin assembly. EGF-mediated clathrin phosphorylation is
      followed by clathrin redistribution to the cell periphery and is the product of
      downstream activation of SRC kinase by EGF receptor (EGFR) signaling. In cells
      lacking SRC kinase, or cells treated with a specific SRC family kinase inhibitor,
      EGF stimulation of clathrin phosphorylation and redistribution does not occur,
      and EGF endocytosis is delayed. These observations demonstrate a role for SRC
      kinase in modification and recruitment of clathrin during ligand-induced EGFR
      endocytosis and thereby define a novel effector mechanism for regulation of
      endocytosis by receptor signaling.

PMID- 10089884
TI  - The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo
      and provides a novel mechanism for pituitary Cushing's disease.
AB  - The neuroendocrine protein 7B2 has been implicated in activation of prohormone
      convertase 2 (PC2), an important neuroendocrine precursor processing
      endoprotease. To test this hypothesis, we created a null mutation in 7B2
      employing a novel transposon-facilitated technique and compared the phenotypes of
      7B2 and PC2 nulls. 7B2 null mice have no demonstrable PC2 activity, are deficient
      in processing islet hormones, and display hypoglycemia, hyperproinsulinemia, and
      hypoglucagonemia. In contrast to the PC2 null phenotype, these mice show markedly
      elevated circulating ACTH and corticosterone levels, with adrenocortical
      expansion. They die before 9 weeks of severe Cushing's syndrome arising from
      pituitary intermediate lobe ACTH hypersecretion. We conclude that 7B2 is indeed
      required for activation of PC2 in vivo but has additional important functions in
      regulating pituitary hormone secretion.

PMID- 10089885
TI  - Longevity, stress response, and cancer in aging telomerase-deficient mice.
AB  - Telomere maintenance is thought to play a role in signaling cellular senescence;
      however, a link with organismal aging processes has not been established. The
      telomerase null mouse provides an opportunity to understand the effects
      associated with critical telomere shortening at the organismal level. We studied
      a variety of physiological processes in an aging cohort of mTR-/- mice. Loss of
      telomere function did not elicit a full spectrum of classical pathophysiological
      symptoms of aging. However, age-dependent telomere shortening and accompanying
      genetic instability were associated with shortened life span as well as a reduced
      capacity to respond to stresses such as wound healing and hematopoietic ablation.
      In addition, we found an increased incidence of spontaneous malignancies. These
      findings demonstrate a critical role for telomere length in the overall fitness,
      reserve, and well being of the aging organism.

PMID- 10089886
TI  - Combinatorial receptor codes for odors.
AB  - The discriminatory capacity of the mammalian olfactory system is such that
      thousands of volatile chemicals are perceived as having distinct odors. Here we
      used a combination of calcium imaging and single-cell RT-PCR to identify odorant
      receptors (ORs) for odorants with related structures but varied odors. We found
      that one OR recognizes multiple odorants and that one odorant is recognized by
      multiple ORs, but that different odorants are recognized by different
      combinations of ORs. Thus, the olfactory system uses a combinatorial receptor
      coding scheme to encode odor identities. Our studies also indicate that slight
      alterations in an odorant, or a change in its concentration, can change its
      "code," potentially explaining how such changes can alter perceived odor quality.

PMID- 10089887
TI  - A spatial map of olfactory receptor expression in the Drosophila antenna.
AB  - Insects provide an attractive system for the study of olfactory sensory
      perception. We have identified a novel family of seven transmembrane domain
      proteins, encoded by 100 to 200 genes, that is likely to represent the family of
      Drosophila odorant receptors. Members of this gene family are expressed in
      topographically defined subpopulations of olfactory sensory neurons in either the
      antenna or the maxillary palp. Sensory neurons express different complements of
      receptor genes, such that individual neurons are functionally distinct. The
      isolation of candidate odorant receptor genes along with a genetic analysis of
      olfactory-driven behavior in insects may ultimately afford a system to understand
      the mechanistic link between odor recognition and behavior.

PMID- 10089888
TI  - Prospective identification, isolation by flow cytometry, and in vivo self-renewal
      of multipotent mammalian neural crest stem cells.
AB  - Multipotent and self-renewing neural stem cells have been isolated in culture,
      but equivalent cells have not yet been prospectively identified in neural tissue.
      Using cell surface markers and flow cytometry, we have isolated neural crest stem
      cells (NCSCs) from mammalian fetal peripheral nerve. These cells are
      phenotypically and functionally indistinguishable from NCSCs previously isolated
      by culturing embryonic neural tube explants. Moreover, in vivo BrdU labeling
      indicates that these stem cells self-renew in vivo. NCSCs freshly isolated from
      nerve tissue can be directly transplanted in vivo, where they generate both
      neurons and glia. These data indicate that neural stem cells persist in
      peripheral nerve into late gestation by undergoing self-renewal. Such persistence
      may explain the origins of some PNS tumors in humans.

PMID- 10089889
TI  - Current controversies in breast cancer management.

PMID- 10089890
TI  - In vitro treatment with retinoids decreases bcl-2 protein expression and enhances
      dexamethasone-induced cytotoxicity and apoptosis in multiple myeloma cells.
AB  - All-trans retinoic acid (ATRA) has been shown to inhibit in vitro growth of
      multiple myeloma (MM) cells, and this effect can be further potentiated by the
      addition of Dexamethasone (DEX). We here extended this study by testing the
      activity of 9-cis retinoic acid (9-cis RA) and 13-cis retinoic acid (13-cis RA),
      both alone and in combination with DEX, in two MM cell lines, U266 and RPMI 8226.
      Furthermore, we aimed at investigating the mechanisms involved in the
      interactions of retinoids and DEX in this setting. 9-cis RA appeared to be the
      most active agent in U266 cell line (IC50 = 1.2 mumol/l vs 10.5 and 9.8 mumol/l
      obtained with ATRA and 13-cis RA, respectively) while, in RPMI 8226 cell line, 9
      cis RA and 13-cis RA were almost equally cytotoxic (IC50 = 1 and 0.8 mumol/l) and
      ATRA was less effective. Co-incubation with DEX resulted in a synergistic
      cytotoxic activity in both the cell lines except for the combinations DEX + 9-cis
      RA in U266 cell line and DEX + 13-cis RA in RPMI 8226 cell line, where the effect
      was merely additive. A synergistic cytotoxic effect of retinoids and DEX was also
      observed on fresh MM cells obtained from 7 patients. Both retinoids and DEX are
      known to be inducers of apoptosis; we verified that the combined inhibitory
      activity of retinoids and DEX could be attributed to an increased induction of
      apoptosis. This effect may be mediated by a reduced intracellular expression of
      BCL-2 protein, which indeed observed after prolonged in vitro treatment with
      retinoids. It has been described recently that an enhanced expression of BCL-2
      protein can contribute to the occurrence of early chemoresistance; the
      downregulation of BCL-2 protein induced by retinoids could thus be exploited, by
      means of novel chemotherapy plus retinoids combinations, in order to improve the
      efficacy of conventional chemotherapy in MM.

PMID- 10089891
TI  - Bcr-abl protein detection in peripheral blood mononuclear cells for follow-up of
      chronic myelogenous leukaemia patients.
AB  - We have assessed the value of p210 protein detection in peripheral blood cells
      for follow-up of chronic myelogenous leukaemia (CML) patients. Quantification was
      achieved by comparing the relative intensities of the p210 bands with those of
      the normal abl protein (p145). Serial dilution of Ph-positive K562 cells with Ph
      negative HL60 or KG1 cells revealed a linear correlation between the p210/p145
      ratio and the number of Ph-positive cells (r = 0.998; p < 0.001) with a
      sensitivity of detecting less than 1% Ph-positive cells in 5 x 10(6) cells.
      Ninety-six consecutive patients were enrolled in the study and a total of 155
      Western blot analyses have been performed and compared to chromosomal analyses of
      bone marrow. Parallel RT-PCR analyses have been performed on 99 occasions. All
      patients with positive cytogenetic findings also probed positive for p210. In 23
      instances p210 was detectable despite negative chromosomal analysis. In 16
      samples these results were confirmed by RT-PCR. In patients with partial
      cytogenetic remission (n = 26) the results of the p210 assay correlated
      significantly with the percentage of Ph-positive metaphases (r = 0.69; p <
      0.001). In conclusion, monitoring of CML patients by quantification of the bcr
      abl protein is a feasible and sensitive alternative to chromosomal analysis of
      bone marrow.

PMID- 10089892
TI  - Circulating haemopoietic progenitor cells in primary and secondary myelofibrosis:
      relation to collagen and reticulin fibrosis.
AB  - The relationship between the extent of bone marrow reticulin and collagen
      fibrosis and the concentration of granulocytic (CFU-GM), erythroid (BFU-E) and
      megakaryocyte (CFU-Mk) progenitor cells in the peripheral blood of patients with
      primary agnogenic myeloid metaplasia (AMM) and secondary myelofibrosis (sMF) has
      not been definitively correlated. We studied 23 patients with established
      diagnosis of AMM and 12 patients with sMF for the extent of reticulin and
      collagen bone marrow fibrosis and for the spontaneous colony (sCFU-GM, sBFU-E and
      sCFU-Mk) formation. The control group consisted of 11 healthy volunteers.
      Trephine biopsy of the posterior iliac crest was performed in all individuals
      studied to determine the type and degree of reticulin and collagen fibrosis.
      Gomori's silver impregnation technique was used. sCFU-GM, sBFU-E and sCFU-Mk
      colony formation was related positively to spleen size, the white blood cell
      counts and the degree of collagen fibrosis in AMM (p < 0.01). Stimulated CFU-GM
      were also significantly correlated with the degree of bone marrow reticulin and
      collagen fibrosis. There was no correlation between the extent of peripheral
      blood progenitor concentration and the degree of bone marrow reticulin or
      collagen fibrosis in sMF and in control individuals. In conclusion, the extent of
      bone marrow fibrosis is significantly correlated with the peripheral blood
      progenitor colony formation in AMM but not in sMF.

PMID- 10089893
TI  - Molecular characterization of two mutations in platelet glycoprotein (GP) Ib
      alpha in two Finnish Bernard-Soulier syndrome families.
AB  - Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and
      macrothrombocytopenia which is caused by a defect in the platelet glycoprotein
      Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and
      thrombin. Here we report the molecular basis of the classical form of BSS in two
      unrelated Finnish patients, both with a life-long history of severe bleeding.
      Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha,
      GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of
      GP V (< 10%) was observed in propositus 1, but a residual amount was found in
      propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was
      compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point
      mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous
      for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either
      of the mutations also had low levels of GP Ib alpha (74-90%). Hence, Bernard
      Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are severely
      affected. Interestingly, both mutations have independently been found in three
      other families in previous reports, suggesting their ancient age or mutational
      'hot spot'.

PMID- 10089894
TI  - Selectivity of von Willebrand factor triplet bands towards heparin binding
      supports structural model.
AB  - Human plasma-derived von Willebrand factor (hp-vWF) and recombinant von
      Willebrand factor (r-vWF) have been fractionated by heparin affinity
      chromatography followed by multimer analysis using SDS-agarose gel
      electrophoresis. Because heparin binding sites are contained in each vWF subunit,
      high molecular weight multimers of r-vWF and hp-vWF, respectively, were eluted
      with higher salt concentration, in comparison to r-vWF and hp-vWF molecules with
      a low degree of multimerization. Heparin affinity chromatography did not affect
      the multimer composition of r-vWF. By contrast, faster migrating satellite bands
      and slower migrating satellite bands of hp-vWF exhibited reduced and increased
      heparin affinity, respectively, compared to the intermediate band of the same
      triplet. Because heparin binding sites are localised in the N-terminal domain of
      the hp-vWF subunit, this result confirms a structural model of hp-vWF (Fischer et
      al., Biochem. J. 1998;331:483-488) suggested recently, in which the slower
      migrating satellite bands have excess of one N-terminal fragment and the faster
      migrating satellite bands lack one N-terminal fragment, respectively, in
      comparison with the corresponding intermediate triplet band.

PMID- 10089895
TI  - A comparative study of CD34+ cells, CD34+ subsets, colony forming cells and
      cobblestone area forming cells in cord blood and bone marrow allografts.
AB  - Cord blood (CB) has become an alternative source of hematopoietic progenitor
      cells (HPCs) for allogeneic transplantation. We have developed a new efficient
      protocol for CB collection. Using this method an average of 17.7 x 10(8) [range
      (6.8-29.6) x 10(8), n = 13] total nucleated cells (TNCs) were harvested. Based on
      recent Eurocord data, which have shown safe engraftment using a threshold dose of
      0.37 x 10(8) CB TNCs/kg body weight (BW), we calculated that six out of thirteen
      CB grafts collected by this method were sufficient to engraft adults. The CB
      derived CD34+ population contained two-fold higher numbers of committed HPCs (CFU
      GM, BFU-E) and six-fold higher numbers of pluripotent HPCs [CD34+/CD38- cells, wk
      5 and wk 8 cobblestone area forming cells (CAFCs)] than the CD34+ population of
      BM. Extrapolation revealed that BM grafts providing the threshold dose for
      allogeneic transplantation of 2 x 10(8) TNCs/kg BW contained nearly 3 times more
      pluripotent HPCs than CB grafts providing the Eurocord threshold dose. The
      assessment of CD34+/CD38(-) cell numbers in CB grafts was highly reproducible and
      correlated well with the in vitro performance of pluripotent HPCs, i.e. numbers
      of CAFCs. We conclude that CB grafts providing high numbers of TNCs have the
      potential to engraft adults and that the enumeration of pluripotent HPCs by flow
      cytometry may be a useful tool to define the ultimate threshold dose for CB
      transplantation.

PMID- 10089896
TI  - Prognostic implications of cytogenetic aberrations in diffuse large B-cell
      lymphomas.
AB  - A single institution series of 81 consecutive, cytogenetically analyzed, diffuse
      large B-cell lymphomas (DLBL), the majority of which treated with anthracycline
      containing combination chemotherapy, were reviewed retrospectively to investigate
      whether the karyotypic pattern or certain abnormalities correlate with survival.
      Clonal chromosome changes were found in 79 of the 81 cases. The prognostic impact
      of the following aberrations, all suggested in previous studies to be associated
      with either shorter or longer survival, were tested: 1q21-23 breakpoints,
      +2/dup(2p), +3/dup(3p), +5, +6, 6q21-25 breakpoints, monosomy 7/der(7p)/i(7q),
      trisomy 7, 14q11-12 breakpoints, monosomy 17/der(17p)/i(17q), trisomy 18, > 4
      marker chromosomes, > 4 breakpoints, and > or = 10 abnormalities. Univariate
      analysis showed that a breakpoint at 1q21-23 or trisomy 6 was associated with a
      shorter survival. However, when adjusted for age, stage, performance status and
      lactate dehydrogenase level, none of the cytogenetic aberrations had an
      independent prognostic value. Thus, the present investigation provides no support
      for any of the above-mentioned abnormalities being of prognostic importance in
      DLBL.

PMID- 10089897
TI  - In vitro effects of insulin-like growth factor-1 (IGF-1) on proliferation and
      constitutive cytokine secretion by acute myelogenous leukemia blasts.
AB  - The effects of insulin-like growth factor 1 (IGF-1) on autonomous proliferation,
      cytokine-dependent proliferation and constitutive cytokine secretion by acute
      myelogenous leukemia (AML) blasts were investigated using serum-free in vitro
      conditions. IGF-1 enhanced AML blast proliferation independent of the presence of
      other exogenous cytokines only for 2 of 21 patients, but for 10 additional
      patients IGF-1 altered blast proliferation in the presence of certain exogenous
      cytokines or cytokine combinations. IGF-1 had minor effects on AML blast cytokine
      secretion only for a subset of the patients (decreased levels for 1 patient,
      increased levels for 7 patients). Our in vitro observations indicate that IGF-1
      can modulate AML blast proliferation and/or cytokine secretion for a subset of
      patients.

PMID- 10089898
TI  - Anaphylactic shock due to recombinant human interleukin-3.

PMID- 10089899
TI  - Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated
      in advanced stages of non-Hodgkin's lymphomas.
AB  - The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were
      measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for
      soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's
      disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients
      were not significantly different from the levels of healthy controls (n = 31).
      However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III + IV.
      Elevated serum levels of sVCAM-1 were associated with significantly poorer
      disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated
      poorly with other known prognostic variables (LDH, sTK and beta 2m) and with
      sICAM-1. None of the tested markers added prognostic information for disease-free
      survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM
      1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different
      histologies were examined and compared with the serum levels of the soluble
      adhesion molecules. No correlation was found between the adhesion molecule
      expression by vascular endothelium and the corresponding serum levels.

PMID- 10089900
TI  - Characterization of defective megakaryocytic development in patients with
      myelodysplastic syndromes.
AB  - Megakaryocytic differentiation of progenitor cells was investigated in nine
      patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia
      [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk
      MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB
      T]). Bone marrow-derived CD34+ cells were enriched to a purity of 87% +/- 2%
      (mean +/- SEM) and assayed in short-term suspension cultures in the presence of
      10 ng/mL of PEGylated recombinant human megakaryocyte (MK) growth and development
      factor (PEG-rHuMGDF) and in addition to 50 ng/mL stem cell factor and 10 ng/mL
      interleukin-3. Cells of the megakaryocytic lineage were identified by flow
      cytometric analysis of CD42b (GP1b) and mature MKs by morphologic criteria.
      Transcription of c-mpl receptor-specific mRNA in the CD34+ cells of these
      patients was investigated by full-length reverse transcriptase polymerase chain
      reaction of the p form of c-mpl as well as of the alternative splice product c
      mpl k. CD34+ cells from seven healthy bone marrow donors served as controls.
      Differentiation along the MK pathway was stimulated in five patients with RA. C
      mpl mRNA was expressed in the CD34+ cells in all cases. In three low-risk
      patients the capacity for in vitro MK growth was absent or minimal even though
      mRNA for c-mpl receptor was detected in the CD34+ cells of this group as well. In
      patients with high-risk MDS, PEG-rHuMGDF stimulated in vitro MK growth from CD34+
      cells in only one of five cases. As in the patients with low-risk MDS, c-mpl mRNA
      for both c-mpl p and c-mpl k splicing products was detected. These results
      indicate that the in vitro response to stimulation with c-mpl ligand
      discriminates between two groups of patients with low-risk MDS and that the
      observed defect in megakaryocytic development is unrelated to the level of c-mpl
      expression in both low-risk and high-risk MDS.

PMID- 10089901
TI  - Occurrence of periodic oscillations in the differential blood counts of
      congenital, idiopathic, and cyclical neutropenic patients before and during
      treatment with G-CSF.
AB  - Using techniques developed in astrophysics to deal with unequally sampled data
      sets, we have analyzed serial differential cell counts from 45 congenital,
      idiopathic, and cyclic neutropenic patients before and during treatment with
      recombinant human G-CSF (rhG-CSF). Our results show that the occurrence of
      significant cycling in the absolute neutrophil count (ANC) of neutropenics not
      classified as cyclical is much more prevalent than had been previously thought,
      and that not all the patients classified as cyclic show significant ANC
      periodicity. In these patients, cycling in more than one cell line may be
      involved. The range of periods encountered in these patients is much broader
      (between 11 and 52 days) than is usually associated with classical cyclical
      neutropenia, and there is no obvious connection between the range of periods and
      the patient's diagnostic category. Administration of rhG-CSF is able to induce
      significant cycling in neutropenic patients that were not cycling prior to
      treatment. In patients who had significant cycling before treatment, rhG-CSF may
      either decrease the period to between 11 and 14 days, or may obliterate any
      statistical evidence of cycling.

PMID- 10089902
TI  - T lymphocytes downregulate granulocyte-macrophage colony-stimulating factor
      secretion from stimulated monocytes by increasing the secretion of monocyte
      derived interleukin-10.
AB  - In previous studies we characterized the cytokine regulation of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating
      factor (G-CSF) secretion by endothelial cells and monocytes and found differences
      in secretion pattern within and between these cell systems. In this study, the
      regulatory effect of T lymphocytes on CSF secretion was examined. T lymphocytes
      had no effect on CSF secretion by endothelial cells. In contrast, the addition of
      T lymphocytes significantly and dose dependently downregulated GM-CSF, but not G
      CSF, secretion by monocytes. In one of our previous studies it was shown that
      interleukin-4 (IL-4) and interleukin-10 (IL-10) were the most potent inhibitory
      cytokines of CSF secretion by monocytes. Both these cytokines are produced by T
      lymphocytes. However, the downregulating effect on monocyte GM-CSF secretion was
      not due to increased secretion of T-lymphocyte-derived IL-4 or IL-10. Instead,
      the presence of T lymphocytes increased the secretion of monocyte-derived IL-10.
      It was shown earlier than IL-10 regulates CSF secretion by monocytes in an
      autocrine manner. Our data indicate that T lymphocytes might interfere with this
      autocrine regulation and thereby influence monocyte function in immune response
      and cell proliferation.

PMID- 10089903
TI  - Expansion of granulocyte colony-stimulating factor/chemotherapy-mobilized CD34+
      hematopoietic progenitors: role of granulocyte-macrophage colony-stimulating
      factor/erythropoietin hybrid protein (MEN11303) and interleukin-15.
AB  - Ex vivo stroma-free static liquid cultures of granulocyte colony-stimulating
      factor (G-CSF)/chemotherapy-mobilized CD34+ cells were established from patients
      with epithelial solid tumors. Different culture conditions were generated by
      adding G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), Flt3
      ligand (Flt3), megakaryocyte growth and development factor (Peg-rHuMGDF), GM
      CSF/erythropoietin (EPO) hybrid protein (MEN11303), and interleukin-15 (IL-15) to
      the basic stem cell factor (SCF) + interleukin-3 (IL-3) + EPO combination. This
      study showed that, among the nine different combinations tested in our 5%
      autologous plasma-containing cultures, only those containing IL
      3/SCF/Flt3/MEN11303 and IL-3/SCF/Flt3/MEN11303/IL-15 significantly expanded
      colony-forming unit granulocyte-macrophage (CFU-GM), burst-forming unit erythroid
      (BFU-E), long-term culture-initiating cells (LTC-IC), CD34+, and CD34+/CD38-
      cells after 14 days of culture. Particularly, the addition of IL-15 to IL
      3/SCF/Flt3/MEN11303 combination produced a significant increase of LTC-IC, with
      an average 26-fold amplification as compared to input cells, without any
      detrimental effect on CFU-GM and BFU-E expansion. This combination also produced
      a statistically significant 3.6-fold expansion of primitive CD34+/CD38- cells.
      Moreover, this study confirms the previously described erythropoietic effect of
      MEN11303, which, in our experience, was the only factor capable of expanding BFU
      E. Compared to equimolar concentrations of GM-CSF and EPO, MEN11303 hybrid
      protein showed a significantly higher capacity of expanding CFU-GM, BFU-E, LTC
      IC, CD34+, and CD34+/CD38- cells when these cytokines were tested in combination
      with IL-3/SCF/Flt3. These cultures indicated that Peg-rHuMGDF addition to IL
      3/SCF/EPO/Flt3 does not affect CFU-GM and BFU-E expansion but, unlike G-CSF or GM
      CSF, it does not decrease the ability of Flt3 to expand primitive LTC-IC. These
      studies indicate that, starting from G-CSF/chemotherapy-mobilized CD34+ cells,
      concomitant expansion of primitive LTC-IC, CFU-GM, BFU-E, CD34+, and CD34+/CD38-
      cells is feasible in simple stroma-free static liquid cultures, provided IL
      3/SCF/Flt3/MEN11303/IL-15 combination is used as expanding cocktail in the
      presence of 5% autologous plasma.

PMID- 10089904
TI  - Relationship between molecular mass and duration of activity of polyethylene
      glycol conjugated granulocyte colony-stimulating factor mutein.
AB  - Proteins conjugated with polyethylene glycol (PEG) have increased in vivo
      activity compared to native proteins. We examined the activity of a variety of
      PEG conjugates prepared with a recombinant mutein of granulocyte colony
      stimulating factor (nartograstim [NTG], KW-2228). The total PEG mass was varied
      by the number and size of the PEG molecules conjugated. In vitro activity,
      determined using a proliferation assay with G-NFS-60 cells, demonstrated an
      inverse relationship between PEG mass and concentration required for half-maximal
      proliferation. In vivo activity was examined by injecting compounds
      subcutaneously into normal mice and determining neutrophil counts at various
      times. Initial experiments in C57BL/6J mice indicated that neutrophil levels were
      significantly elevated 5 days after a single injection of 25 micrograms/mouse of
      each PEG-NTG preparation. More detailed experiments were performed with several
      of the preparations in C3H/HeJ mice lacking endotoxin receptors. The results
      demonstrated that the time after injection at which neutrophil numbers reached a
      maximum increased with increasing size of PEG. Similar results were obtained with
      purified preparations containing 1, 2, or 3 units of 20-kDa PEG per molecule of
      NTG, showing that increasing the extent of PEGylation also increases in vivo
      activity. Dose-response studies with the 20-kDa PEG-NTG demonstrated a plateau at
      doses > 2.7 micrograms/mouse at day 3. The plateau dose increased to 8.4
      micrograms/mouse at day 5, and no plateau was evident at the highest dose tested
      (50 micrograms/mL) at days 7 and 10. These results demonstrate that elevated
      neutrophil levels can be maintained for extended periods following single
      administration of high-molecular-weight PEG-NTG.

PMID- 10089905
TI  - Fas antigen (CD95) in pure erythroid cell line AS-E2 is induced by interferon
      gamma and tumor necrosis factor-alpha and potentiates apoptotic death.
AB  - We investigated the expression of Fas antigen (CD95) in the pure erythroid cell
      line AS-E2 in the presence and absence of interferon-gamma (IFN-gamma) and tumor
      necrosis factor-alpha (TNF-alpha). TNF-alpha induced apoptosis in AS-E2 cells,
      whereas IFN-gamma did not. In culture containing no IFN-gamma or TNF-alpha, AS-E2
      cells expressed little Fas antigen. However, IFN-gamma and IFN-gamma and TNF
      alpha both induced expression of Fas antigen and its mRNA within 24 hours after
      the stimulation. When anti-Fas monoclonal antibody (IgM) was added to AS-E2 cells
      after the induction of Fas expression, AS-E2 cells underwent apoptosis as shown
      by the induction of DNA fragmentation. This apoptotic change was inhibited by an
      inhibitor of caspase-3-like proteases (Ac-DEVD-CHO) and an inhibitor of CED-3/ICE
      family proteases (Z-Asp-CH2-DCB) but not by an inhibitor of caspase-1-like
      proteases (Ac-YVAD-CHO), suggesting a role for caspase-3-like proteases in Fas
      receptor signaling. Although AS-E2 cells expressed Fas ligand mRNA, treatment
      with ZB4, an antibody that inhibits Fas-mediated cell death, failed to suppress
      IFN-gamma- or TNF-alpha-mediated cytotoxicity. These findings suggest that the
      late erythroid progenitor cells are negatively regulated by IFN-gamma and TNF
      alpha, both of which are capable of inducing functional Fas expression.

PMID- 10089906
TI  - Effect of nitric oxide production and oxygen tension on progenitor preservation
      in ex vivo culture.
AB  - Many cell types are capable of expressing inducible nitric oxide synthase (iNOS)
      in response to cytokines or endotoxin. We detected iNOS mRNA by reverse
      transcriptase polymerase chain reaction in CD34+ human bone marrow cells after 48
      hour incubation with interferon-gamma (IFN-gamma)/tumor necrosis factor alpha
      (TNF-alpha) and IFN-gamma/lipopolysaccharide. Based on this finding, we examined
      the effect of nitric oxide (NO) on hematopoiesis and particularly on
      proliferation and survival of CD34+ marrow cells in in vitro culture. When CD34+
      cells were cultured in the presence of an NO donor, S-nitroso-N-acetyl-D,L
      penicillamine (SNAP), a dose-dependent inhibition of cell proliferation was
      observed. Addition of the selective iNOS inhibitor, L-N6-(1-iminoethyl)-lysine
      hydrochloride (L-NIL) at a dose of 500 microM increased the cell counts by 23%
      (range 0-89%). The expansion of total CD34+ cell number was 4-fold with a
      hematopoietic cytokine cocktail compared to 5.2-fold with the addition of L-NIL
      to this combination. At days 7 and 14 of culture, SNAP induced apoptosis in CD34+
      human bone marrow cells detected by an in situ terminal deoxynucleotidyl
      transferase assay. The apoptosis was partially inhibited with the addition of L
      NIL. SNAP also inhibited cell cycling, as evidenced by a 56% decrease in the
      number of cells in S phase after 5 days of culture in the presence of SNAP. To
      investigate if NO production was dependent on oxygen tension, J774A mouse
      macrophage cells were induced with lipopolysaccharide/IFN-gamma, and nitrite
      production measured by the Griess reaction. Nitrite production was persistently
      less in 5% compared to 21% oxygen. CD34+ marrow cells from normal donors were
      also grown under variable oxygen tension, and the cell proliferation in 5% oxygen
      was significantly greater at both 7 and 14 days of culture. CFU-GM colony growth
      also was increased in the low oxygen setting. The concentration of various
      cytokines was measured in CD34+ progenitor culture supernatants, including
      interleukin (IL)-1 alpha, IL-1 beta and TNF-alpha. SNAP increased IL-1 alpha
      production by CD34+ cells as well as from light-density bone marrow cells,
      whereas the effect on IL-1 beta and TNF-alpha production was not significant.
      Manipulation of oxygen tension and the inhibition of production of reactive
      oxygen and nitrogen intermediates may have potential to optimize cell expansion
      and progenitor preservation in ex vivo culture systems.

PMID- 10089907
TI  - Estrone potentiates myeloid cell differentiation: a role for 17 beta
      hydroxysteroid dehydrogenase in modulating hemopoiesis.
AB  - Hormones such as 1 alpha, 25-dihydroxy vitamin D3 (D3), all-trans retinoic acid,
      and 9-cis retinoic acid stimulate differentiation of myeloid progenitor cells via
      their interaction with specific hormone receptors. However, the sensitivity of
      cells to these agents is not merely governed by the expression of their receptors
      and the availability of ligand to bind them. Recent studies from our group
      suggested that the actions of D3 and retinoids on myelopoiesis also are
      influenced by endogenous mechanisms involving other steroid hormones. In this
      study we examined the influence of local estrogen metabolism on the
      differentiation of HL60 cells and normal primitive myeloid progenitor cells.
      Quantitative thin-layer chromatography (TLC) analyses showed that HL60 and normal
      cells are able to generate estrone (E1) from estradiol (E2). Neither cell
      population generated significant amounts of E2 from E1. Reverse transcriptase
      polymerase chain reaction and Northern analyses confirmed that normal and
      leukemic myeloid progenitor cells expressed mRNA for the type I and IV isoforms
      of 17 beta-hydroxysteroid dehydrogenase. Conversion of E2 to E1 was upregulated
      within 24 hours when HL60 cells were treated with either all-trans retinoic acid
      or D3 at doses that induce their differentiation toward neutrophils or monocytes,
      respectively. Similarly, D3-induced monocyte differentiation of normal myeloid
      progenitor cells was associated with increased capacity to generate E1 from E2.
      When HL60 cells or normal myeloid progenitor cells were exposed to exogenous E1
      they became more sensitive to the differentiation-inducing effects of D3. Data
      presented provide further evidence for the local modulation of myelopoiesis by
      intracrine mechanisms. In particular, our findings suggest that local metabolism
      of steroids by normal as well as leukemic myeloid cells influences their
      responsiveness to D3 and retinoids.

PMID- 10089908
TI  - Allogeneic cell-mediated immunotherapy for eradication of minimal residual
      disease: comparison of T-cell and IL-2 activated killer (LAK) cell-mediated
      adoptive immunotherapy in murine models.
AB  - In the course of allogeneic bone marrow transplantation (BMT), avoiding graft
      versus-host disease (GVHD) while retaining the antileukemic effects of the T
      cells remains a major challenge. T-cell depletion (TCD) reduces the incidence of
      GVHD but increases the relapse rate after allogeneic BMT. We attempted to develop
      a regimen that would retain or increase the graft-versus-leukemia effect induced
      by donor T cells while preventing GVHD. Immunosuppressed mice were given
      immunocompetent donor cells, i.e., fresh lymphocytes or lymphokine-activated
      killer (LAK) cells differing from the host in major (MHC) or minor (MiHC)
      histocompatibility antigens. Engraftment of donor cells was documented by
      polymerase chain reaction analysis. Administration of MHC- and MiHC-incompatible
      allogeneic LAK cells, especially in conjunction with recombinant interleukin-2
      (rIL-2), increased disease manifestations and mortality associated with GVHD. On
      the other hand, irradiated LAK cells or TCD-LAK cells prevented GVHD in both mice
      models studied. Phenotypic analysis of LAK cells demonstrated that CD8(+)
      equivalent (Lyt-2) T cells are of significance in aggravation of GVHD. The in
      vitro cytotoxic capacity of LAK cells against MHC-nonrestricted target cells was
      not reduced by either irradiation or TCD. These results provide the background
      for designing improved protocols for immunotherapy of residual disease after BMT.
      In addition, the data imply that antitumor effects may be retained by irradiated
      rIL-2-activated allogeneic cells without causing GVHD. Whereas unmodified
      allogeneic LAK cells can induce more effective graft-versus-leukemia effects at
      the cost of GVHD, irradiated allogeneic donor LAK cells might play some role in
      eradication of minimal residual disease following autologous or allogeneic BMT
      without causing GVHD.

PMID- 10089909
TI  - Synergistic effects of heat and ET-18-OCH3 on membrane expression of hsp70 and
      lysis of leukemic K562 cells.
AB  - We previously reported that cell surface expression of hsp70, the major stress
      inducible member of the 70-kDa heat shock protein family, is inducible by
      nonlethal heat as well as by treatment with the membrane-interactive compound
      alkyl-lysophospholipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18
      OCH3) selectively on human tumor cell lines. Plasma membrane expression of hsp70
      increases selectively the sensitivity of tumor cells to lysis and, therefore,
      might play an important role in the antitumor immune response. Here, we
      demonstrate that a combined treatment consisting of sublethal heat (41.8 degrees
      C) and a noncytotoxic concentration of ET-18-OCH3 (25 micrograms/mL) results in a
      synergistic increase in the amount of cell membrane-bound hsp70 on leukemic K562
      cells and on freshly isolated bone marrow of a chronic myelogeneous leukemia
      (CML) patient, but not on peripheral blood lymphocytes or CD34+ hematopoietic
      progenitor cells of healthy human individuals. Under these conditions the
      repopulating capacity of progenitor cells was not influenced. The increased hsp70
      membrane expression on leukemic K562 cells results in a significantly increased
      sensitivity to lysis mediated by natural killer cells. In contrast to leukemic
      cells, the lysis of peripheral blood lymphocytes and CD34+ progenitor cells that
      lack expression of hsp70 on their plasma membrane was not negatively influenced
      by this treatment. A nonspecific disruption of the plasma membrane could be
      excluded, because treatment with a nontoxic concentration of the detergent
      Tween20 did not have an influence on hsp70 cell surface expression or on the
      sensitivity to lysis. Our findings might have further clinical implications with
      respect to purging of bone marrow from patients suffering from leukemia at
      sublethal conditions to induce a tumor-selective immune response.

PMID- 10089910
TI  - Functional expression of CD80 and CD86 allows immunogenicity of malignant B cells
      from non-Hodgkin's lymphomas.
AB  - We analyzed the accessory function of malignant B cells from non-Hodgkin's
      lymphomas (NHLs). Among the 70 samples of malignant B cells included, four
      patterns of expression of the costimulatory molecules CD80 and CD86 were
      distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or
      both were expressed. To investigate the relevance of these molecules for tumor
      immunogenicity, mixed lymphocyte reactions (MLR) were performed with allogeneic
      responding T cells and malignant B cells from nine NHL patients. Regardless of
      the level of expression of CD80 and CD86, significant proliferation was induced
      in the responder cells. The addition of monoclonal antibodies directed against
      CD80 and CD86 at the beginning of MLR almost completely inhibited this
      proliferation. We show that, during MLR, a high level of expression of CD80 and
      CD86 was induced in NHL B cells. Thus, cooperation between responding and
      stimulator cells seems to occur during MLR, allowing induction of optimal
      accessory function of B cells. We investigated whether malignant B cells cultured
      with CD40-L-transfected L cells in the presence of IL-4 could augment their
      antigen-presenting cell (APC) functions. The culture of NHL B cells in this sytem
      induced strong upregulation of the expression of CD80 and CD86 as well as other
      molecules involved in accessory cell functions (HLA class I, CD54, and CD58). In
      half of the cases, this activation resulted in enhanced proliferation of allo-T
      cells as compared to the proliferation induced by nonactivated malignant B cells.
      Our results show that NHL B cells are able to express functional CD80 and CD86
      and to be fully competent APC. This suggests that the absence of an efficient T
      cell-mediated antitumor response in vivo is not related to a deficiency in the
      APC functions of malignant B cells.

PMID- 10089911
TI  - Endogenous catecholamine synthesis, metabolism storage, and uptake in human
      peripheral blood mononuclear cells.
AB  - Evidence has been obtained that peripheral blood mononuclear cells contain
      dopamine, norepinephrine, epinephrine, and their metabolites. Pharmacologic
      inhibition of tyrosine hydroxylase or monoamine oxidase profoundly affected
      intracellular catecholamines (CTs) and their metabolites, indicating that these
      cells are able to synthesize and breakdown CTs. The sensitivity of intracellular
      CTs to reserpine and the presence of CTs in the extracellular medium suggest that
      CTs are stored and released. Moreover, the increase of extracellular CTs in the
      presence of monoamine uptake blockers point to the presence of functional uptake
      mechanisms. Altogether, these results indicate the existence of a CT lifecycle in
      human mononuclear cells and warrant further studies to investigate the role of
      adrenergic autoregulatory mechanisms in modulation of the immune response and in
      the pathogenesis of diseases involving the immune system.

PMID- 10089912
TI  - Extended culture of multipotent hematopoietic progenitors without cytokine
      augmentation in a novel three-dimensional device.
AB  - The ability to culture multipotent hematopoietic progenitor cells for extended
      periods is of practical importance to both clinical and research efforts
      involving these cells. Conventional techniques for the extended culture of
      hematopoietic progenitor cells (HPCs) have proven largely ineffective in
      sustaining these cells and preserving their multipotency over protracted periods.
      To overcome barriers to extended HPC culture, numerous alternative approaches,
      including cytokine augmentation and co-culture with bone marrow stroma, have been
      explored to enhance HPC maintenance but have generally yielded mixed results. The
      present study examined the ability of a novel, three-dimensional, tantalum-coated
      porous biomaterial (TCPB) to support HPC maintenance and multipotency in long
      term cultures to which no exogenous cytokines have been added. As a follow-up to
      previously published short-term HPC cultures in TCPB, we examined the
      maintenance, phenotype and multipotency of HPCs cultured for up to 6 weeks in the
      TCPB matrix compared to control systems, including fibronectin-coated plastic,
      bone marrow stroma cocultures and other three-dimensional materials. These
      studies indicated that TCPB supports the maintenance of immature progenitors for
      up to 6 weeks in the absence of supplemented cytokines. Further, the results
      demonstrate that the TCPB matrix facilitates and enhances HPC maintenance and
      leads to a 1.5-fold expansion of HPC numbers following 1 week in culture and a
      6.7-fold increase in colony-forming ability following 6 weeks in culture in the
      absence of exogenous cytokines. Under the same conditions, control systems were
      less able to support progenitor viability and multipotency. These findings point
      to new approaches that may improve the in vitro preservation of progenitors and
      may have important implications in clinical areas such as progenitor expansion,
      bone marrow transplantation and gene therapy.

PMID- 10089913
TI  - Uncommon missense and splice mutations and resulting biochemical phenotypes in
      German patients with X-linked chronic granulomatous disease.
AB  - Chronic granulomatous disease is an inherited disease characterized by the
      inability of phagocytes to generate normal amounts of superoxide, leaving
      patients susceptible to opportunistic, life-threatening infections. In the
      majority of cases, cytochrome b558 is absent in the X-chromosomal form of CGD.
      However, the neutrophils from six of nine X-linked CGD patients, reported here,
      expressed normal or decreased amounts of this cytochrome and are referred to as
      "variant" forms. In three of these six variant patients, a roughly proportional
      decrease in cytochrome b558 expression and production of H2O2 were found. In two
      cases this phenotype could be well explained by special splice mutations, whereas
      in the third case it was caused by a missense mutation, predicting Ser 193-->Phe.
      In the other three variant patients, cytochrome b558 expression and H2O2
      production were clearly disproportionate as the generation of H2O2 was much more
      decreased than cytochrome expression. Missense mutations also were found in these
      cases. One of these mutations, predicting Leu 546-->Pro and affecting the
      putative nicotinamide adenine dinucleotide phosphate binding site, led to normal
      levels of cytochrome b558 expression and reduced H2O2 production. In the other
      two mutations, predicting Pro 339-->His and His 338-->Tyr, the putative flavin
      adenine dinucleotide binding site was affected. This could explain the
      corresponding uncommon phenotypes, characterized by zero or trace amounts of H2O2
      production and the expression of relatively high amounts of nonfunctional or low
      functional cytochrome b558, respectively. The only missense mutation found that
      prevented the expression of any cytochrome b558 was caused by a predicted His 222
      ->Arg exchange in one of the three classic cases. The two other classic
      phenotypes were caused by splice mutations.

PMID- 10089914
TI  - Interferon-gamma rescues TNF-alpha-induced apoptosis mediated by up-regulation of
      TNFR2 on EoL-1 cells.
AB  - Recent studies show that apoptosis is important for the resolution of chronic
      inflammation. Using a human myeloblastic leukemia cell line, EoL-1, we
      investigated the effect of interferon-gamma (IFN-gamma), which differentiates EoL
      1 into monocyte/macrophage-like cells on Fas antigen (Fas)- and tumor necrosis
      factor-alpha (TNF alpha)-induced apoptosis. Both TNF and anti-Fas monoclonal
      antibody (CH-11) induced apoptosis of EoL-1 cells. Pretreatment with IFN-gamma
      for 72 hours enhanced the CH-11-induced apoptosis with up-regulation of Fas.
      However, the treatment markedly inhibited the TNF-induced apoptosis. In flow
      cytometric analysis, EoL-1 expressed two types of tumor necrosis factor receptors
      (TNFR1 and TNFR2), and the expression of TNFR2 but not of TNFR1 was up-regulated
      significantly after the IFN-gamma treatment. The TNF-induced apoptosis was
      mimicked by a TNFR1 stimulating antibody (htr-9), and was reversed by a TNFR1
      blocking antibody (H398). Although the TNFR1-mediated cytotoxic signal was not
      affected by IFN-gamma pretreatment, blocking TNFR2 by a specific antagonistic
      antibody (utr-1) canceled the inhibitory effect of IFN-gamma. In conclusion, TNF
      induced apoptosis was mediated preferentially by TNFR1, and the anti-apoptotic
      effect of IFN-gamma was result from up-regulated TNFR2 in EoL-1 cell line. This
      cell line is a useful model to provide new insights into crosstalk among Fas/FasL
      , TNF-, and IFN-gamma-mediated signaling.

PMID- 10089915
TI  - Marrow sensitization to 5-fluorouracil using the ligands for Flt-3 and c-Kit.
AB  - In vivo administration of c-kit ligand (KL) expands early hemopoietic progenitors
      and stem cells and sensitizes clonogenic progenitors to 5-FU-mediated cell death.
      Studies were performed to determine whether the in vivo administration of Flk
      2/Flt-3 ligand (FL) is also capable of sensitizing progenitors to 5-FU. Mice were
      treated with FL (100 micrograms/kg every 12 hours for a total of 3 doses), KL (50
      micrograms/kg, same schedule) or both, either alone or in combination with 5-FU
      (a single 125 mg/kg injection 3 hours before the last dose of cytokine). Femurs
      and spleens were harvested 48 hours following the last dose of cytokine, and the
      total numbers of mononuclear cells and colony forming unit cells (CFU-C) per
      femur and spleen were determined. Statistically significant increases in the
      number of CFU-C per femur were observed in response to FL, KL and FL + KL. In the
      spleen, statistically significant increases in CFU-C were observed only with the
      FL + KL combination. 5-FU alone produced marked reductions in CFU-C both in the
      femur and in the spleen. In the femur, 5-FU-mediated reductions in CFU-C were
      enhanced 3- to 30-fold in the presence of concomitant KL, FL or KL + FL
      administration. Surprisingly, the combination of KL + FL was no more effective in
      sensitizing marrow CFU-C to 5-FU than was KL alone, suggesting that CFU-C that
      are capable of surviving the KL/5-FU combination cannot be driven into cell cycle
      by FL. The effects of concomitant cytokine/5-FU administration in the spleen
      contrasted sharply with those observed in the femur, as FL, KL and FL + KL all
      failed to enhance 5-FU-mediated reductions in CFU-C. The ability of FL + KL to
      stimulate CFU-C expansion in the spleen combined with the inability of this
      cytokine combination to augment 5-FU-mediated progenitor toxicity in the spleen
      supports the contention that cytokine-mobilized progenitors are not in cycle.
      FL's capacity to specifically sensitize marrow to the effects of cytotoxic drugs
      may have applications in bone marrow transplant conditioning regimens.

PMID- 10089916
TI  - Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in
      beta-thalassemia patients: kinetics of mobilization and composition of apheresis
      product.
AB  - beta-Thalassemias are often associated with bone marrow expansion and
      immunomodulation in terms of lymphocyte subsets and cytokine levels in the
      peripheral blood. The mobilization of peripheral blood stem cells (PBSC) by
      cytokines in such a background has not been reported. If achieved, the apheresis
      product could be used as a stem cell back-up for beta-thalassemia patients prior
      to bone marrow transplant. PBSC collection may also become a means for providing
      stem and progenitor cells for gene manipulation and therapy of this disorder. The
      aim of the study was to assess the administration of G-CSF in mobilizing stem and
      progenitor cells in these patients and to compare the kinetics of CD34+ cells and
      lymphocyte subsets with those of healthy PBSC donors. Results showed that the
      CD34+ cells were effectively mobilized by G-CSF (10-16 micrograms/day per kg) in
      20 thalassemia patients and 11 healthy donors. Although no significant difference
      was observed in levels of daily stem cell counts between the two groups of
      subjects, a 1 day delay in achieving peak levels of CD34+ cells was observed in
      the majority of thalassemia patients. The peak increase of CD34+ cells was 21.5
      +/- 6.1-fold and 30.8 +/- 7.6-fold of the basal steady-state levels in
      thalassemia patients and healthy donors, respectively. Similar to the situation
      of healthy donors, G-CSF stimulated essentially the CD34+ cells and the myeloid
      lineage (granulocytes, monocytes) in thalassemia patients and had a slight effect
      on lymphocyte subsets (T-helper, T-suppressor, NK, and B cells) and activation
      (CD25, HLA-DR, and CD45RO). Compositions of the apheresis products, including
      CD34+CD38-, CD34+CD33+ and CD34+HLA-DR- cells, were similar in the two groups of
      subjects. Correlation studies showed that the level of CD34+ cells in the PB is a
      good indicator of that in the apheresis product (r = 0.88, p < 0.001). The study
      has demonstrated that under close monitoring of CD34+ cell levels in PB, the
      mobilization by G-CSF and collection of PBSC in beta-thalassemia patients are
      feasible.

PMID- 10089917
TI  - Adhesion receptor expression by hematopoietic cell lines and murine progenitors:
      modulation by cytokines and cell cycle status.
AB  - Hematopoietic progenitor cells are incubated with cytokine combinations for in
      vitro expansion of stem cells and to enhance retrovirus-mediated gene transfer.
      Optimization of the engraftment of these treated cells would be critical to the
      success of stem cell transplantation or gene therapy. Previous studies
      demonstrated that a 48-hour incubation of donor BALB/c bone marrow with a mixture
      of four cytokines (IL-3, IL-6, IL-11, and SCF), resulted in expansion of
      primitive progenitor/stem cells but a loss of long-term engraftment in
      nonmyeloablated or myeloablated recipients. We have established the expression
      pattern for a number of adhesion receptors by normal hematopoietic progenitors
      and cell lines and the modulation in expression induced by cytokines or cell
      cycle progression to ascertain the molecular basis for such defective
      engraftment. Northern blot analysis demonstrated that the cytokine combination of
      IL-3, IL-6, IL-11, and SCF dramatically down-regulated alpha 4 integrin receptor
      expression in HL-60 cells. Synchronized FDC-P1 cells exhibited modulation of
      alpha 4 expression through cell cycle progression, both by quantitative RT-PCR
      and flow cytometry. Normal murine bone marrow lineage-depleted, Sca+ cells
      expressed a number of adhesion receptors, including alpha L, alpha 1, alpha 3,
      alpha 4, alpha 5, alpha 6, beta 1, L-selectin, CD44, and PECAM as assessed by
      flow cytometry, immunofluorescence, and RT-PCR. There was modulation of the
      expression of several of these receptors after incubation in the four cytokines
      for 24 and/or 48 hours: the proportion of cells expressing alpha L, alpha 5,
      alpha 6, and PECAM increased, whereas the proportion of cells expressing alpha 4
      and beta 1 decreased, after cytokine incubation. There was a demonstrable
      concomitant decline in adhesion of these cells to fibronectin after the cytokine
      incubation, a finding that correlates with the decrease in expression of alpha 4.
      These changes in adhesion receptor expression and function with cytokines and
      during cell cycle transit may be critical to stem cell homing and engraftment
      after transplantation, as multiple receptors could be involved in the process of
      rolling, attachment to endothelium, endothelial transmigration, and migration
      within the marrow space.

PMID- 10089918
TI  - Expression of homing-associated cell adhesion molecule (H-CAM/CD44) on human
      CD34+ hematopoietic progenitor cells.
AB  - We investigated the expression of CD44 molecule on CD34+ hematopoietic progenitor
      cells. Significantly lower expression of CD44 was observed on bone marrow (BM)
      CD34+ cells compared with circulating CD34+ cells in cord blood and peripheral
      blood. Using fluorescence-activated cell sorting, human CD34+ BM cells were
      fractionated into CD44+ and CD44- populations. Immunofluorescence analysis
      revealed that the majority of CD34+CD44- cells expressed B-lymphocyte-associated
      CD10 and CD19 antigens, whereas only a part of CD34+CD44+ cells were positive for
      CD19. Myeloid and erythroid progenitor cells were found predominantly in CD34+
      CD44+ cell fractions. In short-term suspension cultures, cell proliferation and
      G1-->S transition in the cell cycle were enhanced in CD34+CD44+ cells. In
      contrast, a large part of CD34+CD44- cells underwent apoptotic cell death.
      Although co-culture with BM stromal cells could partially prevent CD34+CD44-
      cells from undergoing apoptosis, significant increase of apoptotic cells was
      consistently observed. Furthermore, CD34+CD44- cells plated on BM stromal cells
      could differentiate into CD34-CD44-CD10-CD19+ cells. These findings suggest that
      CD34+CD44- cells expressing CD19 would represent unique B-lymphocyte-committed
      precursors in BM, which might undergo apoptotic cell death in the early steps of
      B-cell differentiation.

PMID- 10089919
TI  - Paclitaxel vs cyclophosphamide in peripheral blood stem cell mobilization:
      comparative studies in a murine model.
AB  - Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It
      also may play a role in mobilization of peripheral blood stem cells (PBSC), as an
      alternative to cyclophosphamide (Cy). We investigated the PBSC-mobilizing
      potential of paclitaxel compared to Cy in a murine model. C57B1/6 mice were
      primed with intraperitoneal injections of Cy (200 mg/kg) or paclitaxel (60 mg/kg)
      and were sacrificed 4, 6, 8, or 10 days later. Spleens were harvested and
      processed to obtain low-density mononuclear cells that were used as PBSC. The
      number of hematopoietic progenitors (CFU-C) on day 4 was significantly higher in
      the paclitaxel group when compared to mice receiving Cy (72.0 +/- 1.8 vs 9.8 +/-
      2.8, p < 0.001). By day 6, CFU-C became significantly higher in the Cy-treated
      group compared to the paclitaxel-treated group (195.6 +/- 31.9 vs 95.8 +/- 20.7,
      p < 0.05) and this trend was maintained. However, the total number of CFU-C
      recovered per spleen was greater in the paclitaxel-treated group (1.27 x 10(5) +/
      0.53 x 10(5) vs 1.06 x 10(5) +/- 0.36 x 10(5), NS). In contrast to paclitaxel,
      mobilization with Cy was associated with marked perturbation in the proportion of
      lymphoid cell subsets in the PBSC population along with functional impairment of
      lymphocytes. After 24 hours of in vitro IL-2 activation, the cytotoxic effector
      cell function of the Cy-mobilized PBSC population was lower than that of
      paclitaxel-mobilized cells when tested against three tumor cell lines (B16,
      melanoma; C1498, AML; and Yak-1, lymphoma). These results indicate that
      paclitaxel is an efficient mobilizer of PBSC, leading to early (day 4 to 6)
      mobilization of PBSC when compared to Cy (day 6 to 8). In addition, paclitaxel
      was associated with less perturbation of phenotypic and functional
      characteristics of cells contained within the mobilized PBSC population.

PMID- 10089920
TI  - Immune reconstitution following allogeneic peripheral blood progenitor cell
      transplantation: comparison of recipients of positive CD34+ selected grafts with
      recipients of unmanipulated grafts.
AB  - We compared the kinetic recovery of lymphocytes and their subsets in two groups
      of patients submitted to allogeneic peripheral blood progenitor cell
      transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by
      positive selection of CD34+ cells (group 1, n = 18) and those receiving
      unmanipulated leukaphereses (group 2, n = 15). Patients were conditioned with
      cyclophosphamide (120 mg/kg) and fractioned total body irradiation (13 Gy, group
      1; 12 Gy, group 2). The mean number (x 10(6)/kg) of CD34+ and CD3+ cells infused
      was 4.0 and 0.67, respectively, in group 1 patients, and 4.7 and 274,
      respectively, for group 2 patients. Graft-versus-host disease prophylaxis
      consisted of cyclosporin A + methylprednisolone for group 1 and cyclosporin A +
      methotrexate for group 2. Median follow-up was 7 months (range 2-8 months) for
      both groups. During the first 6 months post-transplant, CD4+ cell counts were
      lower in group 1 as compared with group 2 (p = 0.014, 0.010, 0.011, 0.0003, and
      0.052 at 0.5, 1, 2, 3, and 6 months, respectively), whereas there was no
      difference at 8 months. The number of CD4+CD45RA+ cells was very low throughout
      the study in both groups, being lower in group 1 than in group 2, especially
      during the first 3 months post-transplant (p = 0.007 and 0.0006 at 1 and 3
      months). Normal levels of CD8+ cells were reached by 1 month post-transplant in
      both groups. TCR gamma delta + cell counts were lower in group 1 than in group 2
      during the first 4 months post-transplant (p = 0.001, 0.004, and 0.04 at 1, 3,
      and 4 months). A normal number of natural killer cells (CD3-CD56+) was achieved 1
      month post-transplant in both groups. B lymphocytes (CD19+) showed low or
      undetectable counts throughout the first 4 months in both groups, achieving the
      normal range at 8 months. These results show that, during the first 6 months
      following allo-PBT with CD34+ selected grafts, the number of CD4+, CD4+CD45RA+,
      and TCR gamma delta + cells is significantly lower than after unmanipulated allo
      PBT; these differences disappeared at 8 months. In contrast, there are no
      differences between transplant groups in the recovery of CD8+, CD19+, and natural
      killer cells.

PMID- 10089921
TI  - Detection of cytomegalovirus proteins by flow cytometry in the blood of patients
      undergoing hematopoietic stem cell transplantation.
AB  - Cytomegalovirus (CMV) infection and associated diseases continue to be a major
      complication encountered by patients undergoing high-dose chemoradiotherapy and
      hematopoietic stem cell transplantation (HSCT). A number of studies revealed that
      identification of CMV in the blood of HSCT patients was a predictor of future CMV
      disease. The purpose of this study was to determine if CMV proteins detected by
      flow cytometry could be a rapid and more quantitative way to monitor CMV
      infections and CMV antigenemia in HSCT patients. Preliminary studies showed that
      CMV immediate early (IE), early (E), and late (L) tegument proteins were
      specifically identified in CMV-infected cell lines and not in uninfected cells.
      We evaluated CMV antigen detection by flow cytometry in blood samples collected
      before and after transplantation in 56 serially collected blood samples from 17
      HSCT patients and CMV protein expression was compared to CMV isolation. CMV IE
      and E proteins were not detected in any of the samples analyzed. However, CMV L
      protein detection by flow cytometry correlated with virus isolation in serially
      collected blood samples. Samples from 14 patients were evaluated by both
      techniques, at the same time intervals. There was a 100% correlation (8/8)
      between the lack of CMV antigen detection by flow cytometry and the failure to
      isolate infectious virus. Moreover, 5 of 6 patients who were positive for CMV L
      antigen by flow cytometry also were positive by virus isolation techniques. When
      flow cytometry and virus isolation did not detect CMV antigen on the same day,
      CMV positivity was first detected by flow cytometry. Then, 1-2 weeks later,
      positive virus isolation was documented. This study indicates that flow
      cytometric identification of CMV antigenemia correlates with isolation of CMV in
      HSCT patients and may be a predictive test for the rapid detection of CMV in the
      blood.

PMID- 10089922
TI  - Washing our hands of the matter.

PMID- 10089923
TI  - A man with a swollen leg and abnormal globulins.
AB  - A 72-year-old man presented with a two-week history of exertional dyspnea and
      nonclaudicatory pain and swelling in the right lower leg. Elevating the leg for
      short periods had not helped. The symptoms had begun soon after he took a
      nonsteroidal anti-inflammatory drug for right shoulder pain but persisted after
      he stopped taking the drug. His history included two-pillow orthopnea, but that
      had not worsened in the last year. He had not experienced chest discomfort.

PMID- 10089924
TI  - Acute dyspnea and tachycardia in a cigarette smoker.

PMID- 10089925
TI  - Case in point. Discoloration due to "chest pen".

PMID- 10089926
TI  - Carpal tunnel syndrome: is it work-related?
AB  - The reported incidence of work-related carpal tunnel syndrome has skyrocketed;
      however, many cases have an underlying systemic cause. A methodical investigation
      -including appropriate imaging studies and laboratory testing--can differentiate
      symptoms that are primarily occupational from those with associated medical
      illness or obesity.

PMID- 10089927
TI  - Thymic function, aging, and AIDS.
AB  - For the first time, physicians are challenged by clinical states in which the T
      cell pool is destroyed postnatally in large numbers of patients. One such state
      is AIDS; another is the immune damage of cancer chemotherapy. Accordingly, study
      of postnatal thymic function is now a matter of clinical urgency. Ongoing work
      may point toward new strategies for repairing a damaged T-cell repertoire.

PMID- 10089928
TI  - Recognizing the faces of hypothyroidism.
AB  - Physicians may not recognize hypothyroidism if they rely on the stereotypical
      picture of the disorder. The age of the patient, stage of the disease, and other
      illnesses or conditions such as pregnancy can change the clinical presentation.
      The signs and symptoms of hypothyroidism are remarkably diverse. Instead of a
      single picture, physicians need a mental gallery.

PMID- 10089929
TI  - Diagnosis and treatment of diastolic heart failure.
AB  - Up to 40% of patients with heart failure have isolated diastolic dysfunction.
      With proper management, the prognosis is generally more favorable than in
      systolic dysfunction. Distinguishing diastolic from systolic dysfunction is
      essential since the optimal therapy for one condition may aggravate the other.
      New echocardiographic methods enable accurate diagnoses.

PMID- 10089930
TI  - Office management of distal radial fractures.

PMID- 10089931
TI  - Anemia and renal failure after acute onset of diarrhea.

PMID- 10089932
TI  - Na+/Ca++ exchanger and myocardial ischemia/reperfusion.
AB  - Myocardial hypoxia and ischemia are characterized by the depletion of ATP and the
      development of intracellular acidosis, which alter cellular ionic homeostasis.
      Specifically, elevated cytosolic free Ca++ concentrations cause cellular injury
      during hypoxia/ischemia and lead to irreversible myocardial damage during
      reoxygenation/reperfusion. An increase in the intracellular Na+ concentration has
      been shown to correlate with Ca++ overload. Although inhibition of Na+/K+
      exchange because of decreased ATP production may be involved, it is more likely
      that intracellular acidosis drives Na+ into the cells via Na+/H+ exchange.
      Experimental evidence supports the notion that Na+/H+ exchange is primarily
      responsible for Na+ influx during hypoxia/ischemia. The accumulation of
      intracellular Na+ may then activate the Na+/Ca++ exchanger causing Ca++ overload.
      Therefore, the Na+/Ca++ exchanger plays a crucial role in cellular injury during
      hypoxia/ischemia and in cell death during reoxygenation/reperfusion. In the past
      few years, the Na+/Ca++ exchanger has been cloned and the structure/function
      relationship studied intensively. Agents which inhibit the Na+/Ca++ exchanger may
      have therapeutic potential for the treatment of ischemic heart disease. These
      advances will greatly accelerate the understanding of the cellular and molecular
      mechanisms underlying the role of the Na+/Ca++ exchanger in the development of
      myocardial damage during hypoxia/ischemia and reoxygenation/reperfusion.

PMID- 10089933
TI  - Sustained hemoconcentration in patients with chronic atrial fibrillation, a
      potential risk for stroke and thromboembolic complications. A retrospective
      study.
AB  - Hemoconcentration has been observed during paroxysms of atrial fibrillation and
      at the early stage of chronic atrial fibrillation. The present study was designed
      to determine how long the hemoconcentration continues after complete transition
      to atrial fibrillation from sinus rhythm by retrospective long-term observation
      of 9 patients with chronic atrial fibrillation and 18 age-gender matched control
      patients. Hematocrit levels significantly increased with transition to chronic
      atrial fibrillation from sinus rhythm (from 44.88 +/- 0.87% to 46.87 +/- 1.12%, p
      < 0.01) and remained high for at least another 4 years. They remained unchanged
      throughout the observation period in the control patients. There is a significant
      difference in the hematocrit level between patients with chronic atrial
      fibrillation and control patients (p < 0.001). The hemoconcentration may present
      a potential risk for stroke and thromboembolic complications.

PMID- 10089934
TI  - Relationship between flow dynamics in the left atrium and hemostatic
      abnormalities in patients with nonvalvular atrial fibrillation.
AB  - To investigate the relationship between left atrial (LA) flow dynamics and
      hemostatic markers in nonvalvular atrial fibrillation (AF), 45 patients with
      nonvalvular AF who had not received anticoagulants were evaluated by
      transesophageal echocardiography. We determined the LA appendage flow and the
      presence of LA spontaneous echo contrast (SEC) or thrombus. We measured plasma
      levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A, D-dimer,
      beta-thromboglobulin, and platelet factor 4 in peripheral blood as hemostatic
      markers. The patients were divided into a low-velocity group (n = 19; sum of peak
      emptying and filling LA appendage flow velocities < 40 cm/s) and a high-velocity
      group (n = 26; > or = 40 cm/s). The maximum LA diameter was significantly greater
      and the LA expansion fraction was significantly smaller in the low-velocity group
      than in the high-velocity group. LA SEC or thrombus was observed in 11 patients
      (58%) in the low-velocity group, but not in any patients in the high-velocity
      group (p < 0.001). The plasma levels of TAT, fibrinopeptide A, D-dimer, beta
      thromboglobulin, and platelet factor 4 were significantly higher in the low
      velocity group than in the high-velocity group. The plasma levels of TAT,
      fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 were significantly
      higher in 8 patients without LA SEC or thrombus in the low-velocity group than in
      26 patients in the high-velocity group. Patients with nonvalvular AF accompanied
      by an enlarged and dysfunctioning LA and a decreased LA appendage flow velocity
      had increased intravascular coagulation-fibrinolysis activity and platelet
      activation. These abnormalities may be closely related to the thrombogenetic
      state in patients with nonvalvular AF.

PMID- 10089935
TI  - Non-dipolarity of heart potentials estimated by magnetocardiography in normal
      subjects.
AB  - We studied non-dipolarity characteristics during ventricular excitation in normal
      adults and children by magnetocardiography (MCG) by recording magnetic field on
      the thorax. The source and currents of the electrical dipole from the onset up to
      60 ms of ventricular excitation were analyzed in 16 adults and 5 children. A
      single equivalent current dipole (ECD) was estimated by Sarvas' formula for the
      sphere model at 1 ms intervals. The non-dipole value (NDV) was calculated from
      the magnetic field strength at each recording point and theoretically estimated
      by ECD, representing an index for the non-dipolarity. At 32-34 ms from the
      beginning of QRS, the mean NDV was a minimum in all subjects suggesting at least
      a non-dipole component during this period. High NDV (over 5%) were present in
      most subjects in both the early and late phase compared to this period. Thirteen
      of 16 adults had a high NDV in the early phase (9.3 +/- 3.0%, mean +/- SD) and
      all 16 subjects had a high NDV in the late phase (21.5 +/- 10.5%). All 5 children
      had high NDV in both the early (10.5 +/- 5.4%) and late phases (16.8 +/- 7.9%). A
      single ECD estimation by MCG showed a relatively low non dipolar component and
      MCG could be applied to the clinical evaluation of cardiac excitation in both
      normal and pathological conditions.

PMID- 10089936
TI  - Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on
      chronic heart failure. Examination by 123I-MIBG imaging.
AB  - To examine the long-term effects of the angiotensin-converting enzyme (ACE)
      inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women,
      mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New
      York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a
      left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of
      enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure
      were old myocardial infarction (n = 7), hypertension (n = 2), and atrial
      fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG)
      imaging, radionuclide angiography, and treadmill exercise test were performed
      before and after the treatment. With enalapril treatment, (1) left ventricular
      ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/-
      14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to
      272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG
      increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed
      image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG
      decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of
      LVEF was significantly correlated with the improvement rates of the H/M ratio and
      washout rate after treatment with enalapril. Thus, the long-term effects of
      enalapril can be observed in the cardiac sympathetic nervous system, and 123I
      MIBG imaging appears to be useful for evaluating the therapeutic effects of
      enalapril on the cardiac sympathetic nervous system in patients with chronic
      heart failure.

PMID- 10089937
TI  - Localization of type IV collagen alpha chain in the myocardium of dilated and
      hypertrophic cardiomyopathy.
AB  - A total of 6 alpha chains [alpha 1 (IV) to alpha 6 (IV)] have been identified in
      type IV collagen. We examined the localization of these chains in the myocardium
      of patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy. The
      localization of alpha 1 (IV)-alpha 6 (IV) in biopsy specimens of 5 patients with
      DCM and 4 with HCM was examined using immunohistochemistry with monoclonal
      antibodies. Both alpha 1 (IV) and alpha 2 (IV) immunostaining formed thin
      homogeneous outlines around myocytes in control hearts. In the DCM specimens,
      alpha 1 (IV) and alpha 2 (IV) immunostaining formed thick and irregular patterns
      around myocytes. Staining for alpha 1(IV) and alpha 2 (IV) was also observed in
      some enlarged intercellular spaces. In 3 DCM hearts, moderate staining for alpha
      1 (IV) and alpha 2 (IV) was observed in small replacement fibrotic lesions. In
      large replacement fibrotic lesions, no alpha 1 (IV) or alpha 2 (IV) staining was
      observed. In the HCM specimens, alpha 1 (IV) and alpha 2 (IV) staining formed
      thick homogeneous patterns around myocytes. In the enlarged intercellular spaces,
      no alpha 1 (IV) or alpha 2 (IV) staining was observed. No labeling for alpha 3
      (IV)-alpha 6 (IV) was observed in any heart examined. In conclusion, the present
      results demonstrate that type IV collagen consisting of alpha 1 and alpha 2
      chains appears in the fibrotic lesions of DCM, indicating its contribution to the
      development of fibrotic changes in the myocardium of DCM patients. In contrast,
      type IV collagen was restricted to the myocyte membrane in the HCM hearts.
      Fibrotic processes in the intercellular spaces may differ between DCM and HCM
      hearts.

PMID- 10089938
TI  - Q wave and non-Q wave myocarditis with special reference to clinical
      significance.
AB  - This study was designed to evaluate the differences in clinical findings between
      patients with and without Q waves in acute myocarditis. Among a total of 24
      patients, eleven patients had Q waves and thirteen did not. Echocardiographic
      findings, in-hospital complications and follow-up results were compared between
      the two groups. In the acute stage, the Q wave group showed significantly higher
      creatine kinase (CK) values and a more impaired left ventricular ejection
      fraction than the non-Q wave group (40 +/- 11% vs 57 +/- 10%, p < 0.001).
      Transient left ventricular hypertrophy was also prominent in the Q wave group.
      The incidence of cardiogenic shock (55%) and conduction disturbances (64%) were
      higher in the Q wave group than in the non-Q wave group (0% and 15%,
      respectively). In-hospital mortality rate was 27% in the Q wave group and 8% in
      the non-Q wave group, respectively. Since rapid improvement occurred in survivors
      with Q waves, long-term prognosis was favorable for the two groups. In
      conclusion, Q waves might indicate a more severe course in early illness.

PMID- 10089939
TI  - Correlation between wave components of the second derivative of plethysmogram and
      arterial distensibility.
AB  - The ratio of two wave components (magnitude of b/a constituting the second
      derivative of the plethysmogram (SDPTG) was correlated with arterial
      distensibility. Eighty-two subjects (33-93 years old) were classified into three
      groups according to the thickness of the intima-media complex of the common
      carotid artery measured by B-mode ultrasonography. One group was non
      atherosclerotic (without pathologic thickening) (nAS) and the other two groups
      atherosclerotic (mild and severe thickening, or plaque formation) (AS-1 and AS
      2). Distensibility (D) of the common carotid artery was calculated from arterial
      dimensions and blood pressure: h/p = D, where h = (Ds-Dd)/Dd; Ds, Dd and p
      represent the inner diameter of the carotid artery at peak systole, at end
      diastole and brachial pulse pressure, respectively. The plethysmogram was
      recorded at the cuticle of the 2nd digit of the left hand, and the SDPTG was
      determined with a 10 msec time constant. D showed a significant negative
      correlation with age in all subjects and in the three separate groups. The
      correlation between age and magnitude of b/a was significantly negative in all
      subjects. This negative correlation was not observed in the nAS group, while it
      was significant in both AS-1 and AS-2. The correlation between magnitude of b/a
      and D was significantly positive in all subjects and in each group. Significant
      differences were found among the three groups for magnitude of b/a and D. These
      results suggest that a decrease in magnitude of b/a or in D was proportional to
      the thickness of the intima-media complex of the carotid artery, that is, the
      development of atherosclerosis. These results provide direct evidence that
      magnitude of b/a of the SDPTG is related to the distensibility of the peripheral
      artery, and suggest that magnitude of b/a is a useful non-invasive index of
      atherosclerosis and altered arterial distensibility.

PMID- 10089940
TI  - Familial hypercholesterolemia kindred in Utah with novel C54S mutations of the
      LDL receptor gene.
AB  - In the course of investigations of coronary artery disease in Utah, we identified
      a family whose proband showed elevated plasma levels of LDL cholesterol. To
      determine the genetic etiology of the lipoprotein abnormalities, we screened DNA
      samples for mutations in all 18 exons and the exon- intron boundaries of the low
      density lipoprotein (LDL) receptor gene. Novel point mutations were identified in
      the proband: a T-to-A transversion at nucleotide position 223, causing
      substitution of Ser for Cys at codon 54 in exon 3 of the receptor gene. This
      amino acid replacement would disrupt one of the disulfide bonds necessary for
      maintenance of the secondary structure of the repeat at the N-terminal of the
      receptor, prevent correct folding of the receptor, and result in defective
      intracellular transport of the receptor.

PMID- 10089941
TI  - Simultaneous evaluations of contractility and energy metabolism of stunned
      myocardium using 31P magnetic resonance spectroscopy.
AB  - A canine model of postischemic myocardial dysfunction (15 min ischemia, 60 min
      reperfusion) was used to evaluate the relationship between energy metabolism and
      myocardial contractile function by on-line measurements of ECG, left ventricular
      pressure, coronary blood flow and regional segment shortening (%SS) with the
      continuous acquisition of 31PMR spectra. Two groups emerged from these studies;
      the first (n = 7) in which regional myocardial %SS remained significantly
      depressed after 60 min of reperfusion (stunned) and the second (n = 5) in which
      regional %SS returned to control levels after 60 min of reperfusion (non
      stunned). Both groups exhibited rapid, similar decreases in %SS and parallel
      rapid decreases in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio with
      the onset of ischemia. The PCr/ATP ratio exceeded control levels in the stunned
      group immediately upon reperfusion and remained significantly above control after
      60 min of reperfusion. Measurements of tissue myocardial creatine kinase (CK)
      revealed a significant decrease in total tissue CK activity in stunned myocardium
      compared to control. A significant inverse relationship (r = -0.904, p < 0.003)
      was found between myocardial tissue CK specific activity and the PCr/ATP ratios.
      We postulate that the elevated PCr/ATP ratio caused by the impairment of energy
      transfer to the contractile apparatus constitutes a contractile dysfunction in
      the postischemic heart.

PMID- 10089942
TI  - Reduced injury and scar in acute myocardial infarctions treated with human growth
      hormone.
AB  - Repair processes of cells submitted to an injury may exhibit an indirect
      identifying feature of its activity, based on the amount of connective tissue
      that could be traced with special stains and morphometry. Hydroxyproline
      concentration in tissue is also an index with which the presence and amount of
      repair mechanisms can be assessed. They may be quantitated appropriately in
      correlation with the end products of collagen, which represent the amount of
      cicatricial tissue. In order to correlate the size of the scar in myocardial
      infarcts with the amount of connective tissue, a determination of hydroxyproline
      levels after 30 days of acute experimental infarctions was performed in 3 groups
      of rats: 10 received a single dose of 2I U of human growth hormone (HGH) per week
      for 4 weeks, in a bolus injection immediately after the infarction was surgically
      induced; 10 received the same dose as above in daily injections during a week.
      Finally, another group of 10 animals which did not receive an active treatment
      served as controls. All animals were sacrificed at the end of a month. A
      morphometric study with Van Gieson stain was performed. Hydroxyproline levels
      were determined. Hydroxyproline levels were considerably lower in hGH-treated
      rats (T) compared to control (C) rats: 3.30 ug/mg +/- 0.1 vs. 4.10 +/- 0.29 (p <
      0.05). Morphometry: T.: 5.23 +/- 2.45 vs. C.: 4.22 +/- 2.15 of the left
      ventricular wall. Three aneurysms were found in C group versus 1 in T. Human
      growth hormone administered to a group of rats with myocardial infarction showed
      obvious dose--effects consisting of a significant diminution of scar tissue in
      treated rats with a proportional fall in the hydroxyproline levels.

PMID- 10089943
TI  - Antiemetic therapy.

PMID- 10089944
TI  - Messenger RNA expression of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in human hepatocellular carcinoma.
AB  - BACKGROUND: The prognosis of patients with hepatocellular carcinoma is relatively
      poor because of the high rate of intrahepatic recurrences. We have previously
      demonstrated an association between enhanced secretion of active matrix
      metalloproteinases (MMPs; gelatinase A and matrilysin) and early recurrence in
      hepatocellular carcinoma. The aim of this study was to examine further the
      relationship between messenger RNA levels of metalloproteinases and their
      inhibitors and behavior of this carcinoma. METHODS: Messenger RNA expression of
      gelatinase A, gelatinase B, matrilysin and tissue inhibitor of metalloproteinases
      (TIMP)-1 and TIMP-2 were analyzed in 30 patients with hepatocellular carcinoma by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The
      results were contrasted with the clinicopathological data of the patients.
      RESULTS: Enhanced mRNA expression of gelatinase A, gelatinase B and matrilysin in
      tumor was observed in 20, 22 and 19 of 30 patients, respectively. Enhanced mRNA
      expression of gelatinase A or gelatinase B and of matrilysin showed trends toward
      presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P =
      0.064), respectively. Concomitant overexpression of gelatinase A and matrilysin
      was associated with portal invasion, intrahepatic metastasis and recurrence
      within the first postoperative year (P < 0.05). A modest increase of mRNA
      expression of TIMP-1 and TIMP-2 in tumor was observed in half of the patients,
      but did not correlate with any clinicopathological features. CONCLUSION: Our
      results suggest that semiquantitative RT-PCR analysis of MMPs may be helpful in
      disease management of patients with hepatocellular carcinoma.

PMID- 10089945
TI  - The location of positive nodes partly influences the prognostic value of the
      number of positive nodes in breast cancer patients.
AB  - BACKGROUND: The aim was to determine whether the number of positive lymph nodes
      or the location of lymph node metastasis (location number) would permit a more
      accurate prediction of prognoses. METHODS: We compared the survival rates of 3922
      patients with primary breast cancer in relation to the location number and the
      number of positive lymph nodes. Survival rates were calculated by the Kaplan
      Meier method and analyzed using the log rank test. RESULTS: Within the n1 alpha
      group, the presence of one or two positive nodes was associated with
      significantly better survival than the presence of three positive nodes. These
      groups should therefore be distinguished. Within the n1 beta group, there was no
      significant difference in survival between patients with four and those with
      seven or more positive nodes. Comparisons of n1 beta and n2 patients after
      subgrouping by the number of positive nodes (4-9 and 10 or more) revealed a
      significantly poorer prognosis in the n2 group. CONCLUSIONS: When the prognosis
      of breast cancer is considered from the viewpoint of lymph node metastasis, the
      location number as described in the General Rules is an excellent classification.
      However, we should be aware of possible differences in the prognosis depending on
      the number of positive nodes, as this is masked by the location number.

PMID- 10089946
TI  - The efficacy and limitations of repeated slide conferences for improving
      interobserver agreement when judging nuclear atypia of breast cancer. The Japan
      National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.
AB  - BACKGROUND: The pathology section of the Japan National Surgical Adjuvant Study
      of Breast Cancer protocol study was set up to establish histological criteria for
      assessing high-risk node-negative breast cancers and standardize the subjective
      criteria used by collaborating pathologists for nuclear grading of cancers.
      METHODS: In order to standardize the nuclear atypia criteria, five slide
      conferences were held. A total of 57 observers assigned nuclear atypia scores to
      119 breast carcinomas that were presented using a slide projector or a TV monitor
      and discussed their histological findings. The percentage interobserver
      agreements per tumor and per conference and kappa value per conference were
      estimated and compared among the conferences. The percentage intraobserver
      reproducibility per tumor between the last two conferences was compared with the
      percentage interobserver agreement for 20 tumors. The kappa value was also
      calculated for each of 27 observers to evaluate scoring reproducibility. RESULTS:
      The percentage interobserver agreement per conference was constant (75-78%)
      throughout the five meetings and the rate of tumors with > 80% agreement per
      tumor became higher in later conferences. The kappa value was 0.42, 0.25, 0.42,
      0.51 and 0.50 for the first, second, third, fourth and fifth conferences,
      respectively. The tumors with a lower percentage interobserver agreement also had
      a lower percentage intraobserver reproducibility and such scoring variations were
      attributed to the intermediate nature of the degree of tumor atypia. In 26 of 27
      observers, intraobserver agreement for 20 tumors was estimated from the kappa
      value to range from moderate to almost perfect. CONCLUSION: We concluded that the
      repeated slide conferences conducted by the pathology section were an effective
      means of standardizing the subjective histopathological criteria used to assess
      tumors. However, the achievement of a good scoring agreement would be difficult
      for tumors with an intermediate degree of atypia.

PMID- 10089947
TI  - Number and anatomical extent of lymph node metastases in gastric cancer: analysis
      using intra-lymph node injection of activated carbon particles (CH40).
AB  - BACKGROUND: The long-term survival of 200 patients with gastric cancer who
      underwent radical gastrectomy was analyzed with respect to the number and
      anatomical extent of lymph node metastasis. All of the patients received intra
      lymph node injection of fine activated carbon particle solution (CH40) during
      surgery. METHODS: The average number of resected lymph nodes increased in line
      with the anatomical level of lymph node dissection; 32.5 per patient in D1, 42.3
      in D2, 3 and 66.3 in D4. The percentage of blackened lymph nodes without
      metastasis (42.4%) was slightly higher than that of lymph nodes containing
      metastasis (37.2%), but the difference was not statistically significant. Of the
      200 patients, 61 (30.5%) had microscopic evidence of metastatic lymph node
      involvement. Twenty-two patients had between one and three metastatic lymph
      nodes, 19 had between four and nine and 20 patients had more than nine. The 5
      year survival rate was 93.1% in patients without lymph node metastasis, 71.9% in
      patients with 1-8 metastatic nodes, 36.1% in patients with 4-9 nodes and 19.2% in
      patients with > 9 nodes. RESULTS: The 5-year survival rate according to the
      anatomical extent of metastatic lymph nodes was 93.1% in n0, 63.1% in n1, 37.9%
      in n2, 27.8% in n3 and 0% in n4. The number of metastatic lymph nodes and also
      their anatomical extent were identified as independent prognostic factors for
      survival by multivariate analysis. CONCLUSION: The number and anatomical extent
      of metastatic lymph nodes have similar impacts on prognosis in gastric cancer.

PMID- 10089948
TI  - Adjuvant therapy with oral fluoropyrimidines as main chemotherapeutic agents
      after curative resection for colorectal cancer: individual patient data meta
      analysis of randomized trials.
AB  - BACKGROUND: Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being
      studied for adjuvant chemotherapy of curatively resected colorectal cancers. To
      evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual
      patient data (IPD) meta-analysis of randomized clinical trials was performed in
      Japan as an inter-trialist group study. METHODS: Data from the three clinical
      trials in which postoperative adjuvant therapy with o-FPs was compared with
      surgery alone in patients with colorectal cancer were sought. IPD from a total of
      4960 patients with follow-up periods of at least 5 years were analyzed. RESULTS:
      The results of the meta-analysis on an 'intention to treat' basis demonstrated a
      significant benefit of o-FPs in terms of the disease-free survival (DFS) of the
      total patients [risk ratio (RR) 0.830, 95% confidence interval (CI) 0.742-0.929,
      P = 0.001]. o-FPs were also demonstrated to be effective for survival in rectal
      cancer (RR 0.857, 95% CI 0.734-0.999, P = 0.049) and in Dukes'C colorectal cancer
      (RR 0.828, 95% CI 0.711-0.965, P = 0.016). CONCLUSION: The results suggest the
      advantage of long term o-FPs, possibly with the injection of mitomycin C, for
      prognosis for curatively resected colorectal cancer patients.

PMID- 10089949
TI  - Antiemetic efficacy of granisetron: a randomized crossover study in patients
      receiving cisplatin-containing intraarterial chemotherapy.
AB  - BACKGROUND: Cisplatin (CDDP) is one of the most active chemotherapeutic agents
      but is among the most emetogenic drugs. The emetic side-effects of CDDP
      containing intraarterial chemotherapy have not been evaluated in a prospective
      randomized trial and the efficacy of serotonin antagonists in preventing the
      emesis associated with this method of CDDP administration has not been assessed.
      METHODS: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks
      through intraarterial catheters placed in the bilateral internal iliac arteries.
      Patients were classified into two groups: granisetron treatment group (group G)
      and no treatment group (group NG) with the first course of chemotherapy, crossing
      over with the second course. The patients in group G received granisetron 40
      micrograms/kg by intravenous infusion. RESULTS: Although intraarterial CDDP
      administration produced less emesis than intravenous CDDP administration, at the
      same concentration, gastrointestinal toxicity is still the most unpleasant side
      effect for patients. Granisetron administration significantly reduced nausea and
      vomiting during the acute emetic phase (an evaluation of treatment as very
      effective and effective was made in 89% in group G and 33% in group NG (P <
      0.001). Complete control of emesis was achieved in 68 and 18% of patients in
      groups G and NG, respectively (P < 0.0001). CONCLUSION: A single prophylactic
      infusion of granisetron was effective in preventing the nausea and vomiting
      associated with intraarterial CDDP-containing therapy.

PMID- 10089950
TI  - Tropisetron (Navoban) in the control of nausea and vomiting induced by combined
      cancer chemotherapy in children.
AB  - BACKGROUND: We aimed to assess the potency and efficacy of tropisetron, a 5-HT3
      receptor antagonist, in the prevention of nausea and emesis observed in the
      pediatric patient population taking various chemotherapy protocols. METHODS:
      Tropisetron (Navoban) was given to 100 children (62 boys and 38 girls aged 6
      months to 15 years) with various malignancies. Patients received tropisetron
      during one or more courses of emetogenic chemotherapy for a total of 350 courses
      administered intravenously or intravenously and intrathecally. Tropisetron (0.2
      mg/kg/day, maximum: 5 mg/day) was administered as a single intravenous dose
      slowly, before the start of chemotherapy on day 1 and intravenously or by mouth
      on subsequent days (median treatment duration: 5 days). RESULTS: The patients
      receiving cytotoxic chemotherapy had a 70% complete response rate and a 24%
      partial response rate during the first 24 h period of the first course. We
      observed headache (five courses), diarrhea (three courses) and loss of appetite
      (one course) as side-effects (2.5%). CONCLUSION: Tropisetron is safe, effective,
      easy to use, has no serious side-effects and can be recommended for pediatric
      patients. The efficacy of tropisetron may be enhanced by the addition of
      corticosteroids in patients receiving highly emetogenic cancer chemotherapy.

PMID- 10089951
TI  - Epidemiological analysis of site relationships of synchronous and metachronous
      multiple primary cancers in the National Cancer Center, Japan, 1962-1996.
AB  - BACKGROUND: Multiple primary cancer (MPC) has been recognized as a problem
      commonly encountered in routine medical practice. A study of MPC is necessary not
      only to provide insights into the etiology of cancer, but also to provide
      information for effective medical care by clinical oncologists. METHODS: A cohort
      of 49,751 cancer patients who were admitted to the National Cancer Center
      Hospital between 1962 and 1996 was used to study the site relationship of MPC.
      Logistic and Poisson regression analyses using an internal reference group within
      the cohort were applied for the calculation of the prevalence odds ratio (POR)
      for site relationships of synchronous MPC and the incidence rate ratio (IRR) for
      those of metachronous MPC. RESULTS: Three site combinations with elevated risks
      for both synchronous and metachronous MPCs, eight with elevated risk for
      synchronous MPC, five with elevated risk for metachronous MPC and six with
      decreased risk for synchronous MPC were identified with statistical significance.
      Among them, the increased risk of metachronous stomach cancer following lymphoma
      and myeoloma (POR = 1.0 and 1.1, P > 0.05; IRR = 2.5, P < 0.05) and the inverse
      site-correlation of synchronous MPC between [trachea, bronchus and lung] and
      other sites of the upper aerodigestive tract [lip, oral cavity and pharynx] (POR
      = 0.5 and 0.3, P < 0.05) and esophagus (POR = 0.7 and 0.3, P < 0.05) have not
      been reported previously. CONCLUSIONS: Our results suggest that interventions for
      lymphoma and myeloma might affect the development of subsequent stomach cancer
      and additional etiological factors other than tobacco smoking are associated with
      the development of cancer in the upper aerodigestive tract.

PMID- 10089952
TI  - A case of advanced esophageal cancer showing a long-term complete response with
      chemotherapy with nedaplatin alone.
AB  - We describe a case of advanced esophageal cancer treated successfully by
      chemotherapy with nedaplatin alone. A 60-year-old male with type 2 advanced
      esophageal cancer, which was located in the upper part of the esophagus and had
      invaded adjacent organs, was treated with nedaplatin 150 mg/body (100 mg/m2)
      given intravenously every 4 weeks from January 6, 1991. He achieved a partial
      response (PR) and was discharged in March 1991. Subsequently, he received
      nedaplatin 75 mg/body in an out-patient setting almost every month until August
      1992. Toxicities were tolerable and included mild thrombocytopenia and
      nausea/vomiting. From serial evaluation in October 1993, the esophageal tumor was
      not observed. After 7 years since initial chemotherapy was administered, he still
      survives without the disease.

PMID- 10089954
TI  - Detection of lung cancer by helical CT scan: a new method of mass screening.

PMID- 10089953
TI  - A case of a malignant melanoma with late metastases 16 years after the initial
      surgery.
AB  - We report a case of a pulmonary metastasis 16 years after the initial surgery for
      a malignant melanoma. The patient was a 58-year-old Japanese man. In 1976, he had
      a pigmented skin lesion with a diameter of 8 mm on his right third finger. He
      received an amputation of the finger and a dissection of the right axillary.
      Histological examinations of the tumor revealed a feature of a malignant melanoma
      with infiltration of the papillary layers of the dermis, 1.5 mm in thickness. The
      histological subtype was considered to be an acral lentiginous melanoma with a
      mixed spindle-epithelioid cell pattern. There was no regional lymph node
      metastasis. In December 1992, when he was 74-years-old, a round tumor in the left
      lower lung was discovered by chest radiography. In February 1993, he received a
      left lower lobectomy of the lung. Histological examination revealed a feature of
      a malignant melanoma with predominantly epithelioid cells and this was considered
      to be a metastasis from the initial skin lesion. Five months after the lobectomy,
      he died from a hemorrhage of a metastatic brain tumor. This case indicated the
      importance of periodic, life-long follow-up in treating malignant melanomas.

PMID- 10089955
TI  - Effects of acute thyroxin depletion on hearing in humans.
AB  - OBJECTIVE: To study the physiologic effect of acute thyroid hormone depletion on
      hearing and the function of outer hair cells. DESIGN: Audiologic and otoacoustic
      emission testing of subjects undergoing total thyroidectomy before surgery and up
      to 6 weeks after surgery. Magnitude of thyroxin depletion monitored by serum
      thyroid-stimulating hormone levels. SETTING: Hearing research laboratory at a
      state university. SUBJECTS: Ten patients undergoing total thyroidectomy. MAIN
      OUTCOME MEASURES: Detection of hearing loss on audiogram and decrease or
      disappearance of otoacoustic emissions as a result of acute thyroxin depletion.
      RESULTS: No significant changes in the audiogram and otoacoustic emission
      configurations were detected, although thyroid-stimulating hormone levels became
      elevated after total thyroidectomy. CONCLUSION: Although thyroid hormone is
      thought to play a role in the physiology of hearing in humans, no deleterious
      effects on hearing can be identified up to 6 weeks after thyroxin depletion.

PMID- 10089956
TI  - Cochlear reimplantation.
AB  - OBJECTIVE: A small number of multichannel cochlear implant (CI) recipients
      require reimplantation. This study describes the causes of failure, surgical
      technique, and hearing outcomes in a consecutive series of 16 patients undergoing
      reimplantation of multichannel devices. We hypothesize that reimplantation is
      safe and that hearing results are at least as good as those measured following
      primary implantation. STUDY DESIGN: Retrospective analysis of consecutive
      clinical series. METHODS: Chart analysis of 191 consecutive CI operations
      performed at the University of Miami Ear Institute between 1990 and 1997 revealed
      16 patients who received a second multichannel device. All but one had a minimum
      follow-up of 1 year after reimplantation. Ten of these patients had initial
      implantation performed by us, and six were initially operated on elsewhere. Main
      outcomes of the initial procedure were compared with those of the reimplantation,
      including electrode insertion length, number of channels programmed, and
      audiometric results. In addition, cause of failure and relevant surgical findings
      at the second procedure are described. RESULTS: There were no surgical
      complications after reimplantation surgery. Device failure was the most frequent
      cause for reimplantation. Time between initial implantation and failure ranged
      from 0 to 46 months (mean, 22.4 mo; median, 23 mo). Common intraoperative
      findings include mastoid fibrosis, bone growth at the cochleostomy, and skin flap
      breakdown. Following reimplantation, mean length of insertion, number of channels
      actively programmed, and speech recognition scores were at least as good as
      findings before initial implant failure. CONCLUSION: CI reimplantation is safe
      and effective.

PMID- 10089957
TI  - Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle.
AB  - OBJECTIVE: The purpose of this study was to develop a technique to investigate
      the regeneration of utricular hair cells in the adult pigeon (Columba livia)
      following complete hair cell loss through administration of streptomycin. STUDY
      DESIGN: Experimental animal study. METHODS: Animals were divided into four
      groups. Group 1 received 10 to 15 days of systemic streptomycin injections.
      Animals in Groups 2 and 3 received a single direct placement of a 1-, 2-, 4-, or
      8-mg streptomycin dose into the perilymphatic space. Animals in Groups 1 and 2
      were analyzed within 1 week from injection to investigate hair cell destruction,
      whereas Group 3 was investigated at later dates to study hair cell recovery.
      Group 4 animals received a control injection of saline into the perilymphatic
      space. Damage and recovery were quantified by counting hair cells in isolated
      utricles using scanning electron microscopy. RESULTS: Although systemic
      injections failed to reliably achieve complete utricular hair cell destruction, a
      single direct placement of a 2-, 4-, or 8-mg streptomycin dose caused complete
      destruction within the first week. Incomplete hair cell loss was observed with
      the 1-mg dose. Over the long term, regeneration of the hair cells was seen with
      the 2-mg dose but not the 8-mg dose. Control injections of saline into the
      perilymphatic space caused no measurable hair cell loss. CONCLUSIONS: Direct
      placement of streptomycin into the perilymph is an effective, reliable method for
      complete destruction of utricular hair cells while preserving the regenerative
      potential of the neuroepithelium.

PMID- 10089958
TI  - Short-term objective and long-term subjective results of laser-assisted
      uvulopalatoplasty for obstructive sleep apnea.
AB  - OBJECTIVES: To determine the short-term and long-term effects of laser-assisted
      uvulopalatoplasty (LAUP) on symptoms and polysomnographic measures in patients
      with obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Prospective
      assessment of outcomes after LAUP in patients with OSAS. METHODS: Fifty-nine
      patients with OSAS underwent LAUP, and 36 completed postoperative sleep studies.
      Questionnaires ranking snoring and apneic symptoms were completed by the patient
      and bed partner before LAUP, 6 to 12 weeks after LAUP, and in the long term (> 2
      years). RESULTS: The apnea index decreased from 14.4 to 5.8 (P = .0012),
      respiratory disturbance index (RDI) decreased from 28.1 to 7.9 (P = .0046), and
      the mean lowest oxyhemoglobin saturation increased from 80.6% to 84.0% (P =
      .055). The RDI was reduced to 10 or less in 44.4% of patients. Subjective
      questionnaires showed statistically significant improvements in snoring, morning
      fatigue, morning headaches, daytime somnolence, and daytime psychometric
      measures. The symptomatic improvement persisted in the long term. CONCLUSIONS:
      LAUP is an effective method for the management of OSAS. We have demonstrated
      short-term improvement in polysomnographic measures and short-term and long-term
      improvement in subjective measures.

PMID- 10089959
TI  - Quantification of lymph nodes in selective neck dissection.
AB  - OBJECTIVES: Provide reference for surgeon and pathologist regarding expected
      yield from selective neck dissections. Quantify lymph nodes obtained from cadaver
      dissection based on current nodal classification and compare with clinical
      series. STUDY DESIGN: 1. Quantification of lymph nodes at levels I-V harvested
      from human cadavers and correlation with nodal grouping for supraomohyoid (I-III)
      and lateral (II-IV) neck dissections. 2. Retrospective review of operative
      specimens from clinical neck dissections for lymph node quantity. METHODS: 1.
      Twenty radical neck dissection specimens, harvested from 10 fresh human cadavers
      without evidence of head and neck cancer, were separated by nodal level for gross
      and microscopic examination by a pathologist. The quantity of nodes obtained per
      level for each specimen was tabulated. 2. Charts of patients treated with neck
      dissection for squamous cell carcinoma were reviewed and tabulated for type of
      dissection and number of lymph nodes reported. RESULTS: In the 20 cadaver neck
      dissections, the average number of lymph nodes removed for levels I-V was 24,
      with 13 for levels I-III and 19 for levels II-IV. In the clinical review, 98
      total neck dissections were included. In the six supraomohyoid dissections, an
      average of 20 lymph nodes (range, 14-26) were found, with an average of 30
      (range, 15-43) in the 11 lateral compartment specimens. In 81 radical or modified
      radical dissections, an average of 31 nodes (range, 19-63) was reported.
      CONCLUSIONS: The number of lymph nodes removed in selective neck dissection
      should be comparable to that of the corresponding levels in radical neck
      dissection, provided that strict adherence to surgical boundaries is maintained.
      Dissection of normal cadavers provides a reference for the surgeon and the
      pathologist but may under-represent lymph node quantity in the diseased state.

PMID- 10089960
TI  - Intranasal verrucous carcinoma: relationship to inverting papilloma and human
      papillomavirus.
AB  - OBJECTIVES: To establish the incidence, appearance, behavior, and appropriate
      treatment of intranasal verrucous carcinoma and determine its relationship to
      inverting papilloma and human papillomavirus (HPV). STUDY DESIGN: Retrospective
      review of all cases of intranasal verrucous carcinoma seen at the Mayo Clinic
      from 1960 through May 1996. METHODS: Retrospective chart review and data
      collection for age, sex, smoking history, location, association with inverting
      papilloma, treatment, recurrence, and follow-up. Polymerase chain reaction (PCR)
      testing for the presence of HPV DNA was performed on all specimens. RESULTS: Of
      the 13 patients identified, most presented with nasal obstruction (10) or a
      noticeable intranasal lesion (8). The maxillary sinus was the extranasal site
      most often involved. Five patients had verrucous cancer develop in an inverting
      papilloma, and one had squamous cell carcinoma with the verrucous component (a
      hybrid tumor). All but one patient underwent surgery as initial treatment; only
      one patient had preoperative radiation therapy. Surgical procedures ranged from
      local excision to a craniofacial resection. Follow-up ranged from 2 months to 32
      years (mean, 6.5 y). Four patients had a single recurrence and two tumors
      recurred a second time. No metastases developed and no one died from the tumor.
      In seven patients (10 specimens), DNA was successfully amplified for PCR testing,
      and no HPV DNA was detected. CONCLUSIONS: When verrucous tumors are discovered
      early, they can be treated effectively with wide local excision. In some cases, a
      more extensive procedure may be required. A possible role for HPV in the etiology
      of these tumors was not found.

PMID- 10089961
TI  - Nasal alar reconstruction: a critical analysis using melolabial island and
      paramedian forehead flaps.
AB  - OBJECTIVES: To qualitatively and quantitatively describe aesthetic and functional
      outcomes following Mohs ablative surgery involving the alar subunit, using a
      paramedian or subcutaneous melolabial island flap. STUDY DESIGN: Retrospective
      review. METHODS: A single surgeon's results in 38 consecutive patients were
      analyzed. Objective measures (alar rim thickness, donor scar width and length),
      subjective assessment (seven aesthetic parameters) by three academic
      otolaryngologists, and patient satisfaction questionnaires were evaluated.
      Student t test was used to ascertain statistically significant differences
      between reconstructive groups. RESULTS: Questionnaire results demonstrate a
      significant (P = .026) difference in donor site rating favoring melolabial group
      responses. Objective scar measurements and subjective ratings of textural quality
      and alar notching also favored melolabial reconstructions. CONCLUSIONS: More
      favorable aesthetic and functional outcomes are seen with single subunit
      cutaneous alar defects reconstructed with the melolabial island flap than with
      deep composite or extensive unilateral nasal defects reconstructed with the
      paramedian forehead flap.

PMID- 10089962
TI  - Olfactory secretion and sodium, potassium-adenosine triphosphatase: regulation by
      corticosteroids.
AB  - OBJECTIVES: To investigate the cellular distribution and relative intensity of
      the immunoreactivity associated with the expression of sodium, potassium
      adenosine triphosphatase (Na, K-ATPase) in cells of the olfactory mucosa. Second,
      changes in the activity of this enzyme in the olfactory mucosa are correlated
      with changes in the circulating corticosteroid aldosterone. METHODS: Combination
      of immunohistochemical and biochemical techniques were employed to examine the
      olfactory Na, K-ATPase. RESULTS: Within the olfactory epithelium, the Na, K
      ATPase immunoreactivity was greatest at the supranuclear region of sustentacular
      cells and/or dendrites of olfactory receptor neurons (ORNs). Cell bodies of ORNs
      demonstrated moderate immunoreactivity, whereas the duct cells of Bowman's gland
      exhibited moderate to intense immunoreactivity. Acinar cells of the Bowman's
      gland were the most intensely stained components of the lamina propria,
      exhibiting strong immunoreactivity at the basolateral plasma membrane domains of
      the acinar cells and less within the cytoplasm. Binding of ouabain, a specific
      inhibitor of Na, K-ATPase, was significantly elevated for aldosterone-injected
      versus sham-injected controls. CONCLUSION: These results suggest that olfactory
      Na, K-ATPase is regulated by the systemic corticosteroid aldosterone. The results
      are consistent with the hypothesis that corticosteroids regulate olfactory
      secretion.

PMID- 10089963
TI  - Limitations of adenovirus-mediated interleukin-2 gene therapy for oral cancer.
AB  - OBJECTIVE/HYPOTHESIS: Adenoviral interleukin-2 (AdV-IL-2) gene therapy has
      previously not proven effective in treating established murine oral cancer. We
      hypothesize that the intratumoral level of IL-2 expression is a major limiting
      factor in treatment outcome. METHODS: A microscopic disease and established oral
      cancer murine model was used to test this hypothesis. IL-2 gene transfer was
      performed with a recombinant adenovirus vector. RESULTS: Tumor cells were
      transduced in vitro with AdV-IL-2 and subsequently implanted into the floor of
      the mouth in C3H/HeJ mice. IL-2 expression in vitro ranged from 990 to 1,050
      pg/10(6) tumor cells. This microscopic disease treatment resulted in either
      complete tumor regression or a dramatic decrease in tumor progression. Cytolytic
      T-cell (CTL) assays demonstrated a predominance of CD8-specific, T-cell-mediated
      tumor killing. Reducing IL-2 expression by half with a mixture of 1:1 transduced
      to nontransduced tumor cells eliminated the antitumor effect and decreased the
      CTL response. These findings support the presence of a critical "threshold" of IL
      2 expression. Adenovirus repurification and amplification allowed isolation of a
      twofold-higher-titer AdV-IL-2 vector. Treatment of established tumors with the
      higher-titer AdV-IL-2 at a new maximal dose of 1.4 x 10(9) plaque-forming units
      (pfu) increased in vivo IL-2 expression to 1,127 pg/10(6) cells and generated a
      significant antitumor response. Complete regression of established tumors,
      however, could not be achieved, and we noted a decrease in IL-2 expression well
      below the threshold at 1 week after treatment. Upon repeat maximal AdV-IL-2
      injection in vivo, a greater antitumor effect and increased CTL response was
      seen, but also, 28% of the animals died of IL-2 toxicity. CONCLUSION: Although
      limited by expression and toxicity as a single-treatment strategy for established
      tumors, AdV-IL-2 gene therapy should be considered a potential component of
      combination therapy strategies.

PMID- 10089964
TI  - Physiologic and hypertonic saline solutions impair ciliary activity in vitro.
AB  - OBJECTIVE/HYPOTHESIS: Physiologic saline (NaCl 0.9%) is commonly used in treating
      acute and chronic rhinosinusitis. Moreover, physiologic saline is used as a
      control medium, vehicle, or solvent in studies on ciliary beat frequency (CBF).
      Hypertonic saline (NaCl 7% and 14.4%) has been applied in attempts to enhance
      mucociliary transport in patients with cystic fibrosis or asthma and in healthy
      subjects. Therefore the objective of this study is to document in vitro effects
      of saline solutions in different concentrations on CBF. STUDY DESIGN:
      Experimental, in vitro. METHODS: The effects on CBF of cryopreserved mucosa of
      the sphenoidal sinus was measured by a photoelectrical method. Initial
      frequencies, measured in Locke-Ringer's solution (LR), were compared with CBF
      after exposure to NaCl in concentrations of 0.9%, 7.0%, and 14.4% (w/v). RESULTS:
      NaCl 0.9% has a moderately negative effect on CBF. The 7% solution leads to a
      complete ciliostasis within 5 minutes, although this effect turns out to be
      reversible after rinsing with LR. A hypertonic solution of 14.4% has an
      irreversible ciliostatic effect. CONCLUSION: LR is an isotonic solution that has
      no effect on CBF. Therefore it is probable that this solution is more appropriate
      than saline for nasal irrigation and nebulization or antral lavage. Moreover, the
      results of this study suggest that mucolytic effects induced by hyperosmolarity
      should be attained preferably with hypertonic saline 7% in patients with cystic
      fibrosis or asthma. At this concentration, the ciliostatic effect is reversible,
      whereas irreversible changes are to be expected at higher concentrations.

PMID- 10089965
TI  - Bone density measurements of the paranasal sinuses on plastinated whole-organ
      sections: anatomic data to prevent complications in endoscopic sinus surgery.
AB  - OBJECTIVE/HYPOTHESIS: Although anatomic data regarding the gross anatomy of the
      paranasal sinuses are available, severe complications of endonasal sinus surgery
      (ESS) are frequently reported. To understand and to avoid these complications,
      density of bony walls of the paranasal sinuses were studied in this report.
      Special attention was given to the analysis of the bone density in regions where
      minor and major complications occur in ESS. METHODS: Thirty cadaver heads were
      embedded in epoxy resin. The plastic blocks were sectioned with a diamond-coated
      wire saw into 1.0-mm thick, parallel slices in axial, coronal, and sagittal
      planes for 10 specimens each. The slices were x-rayed and scanned with a
      computerized image analyzing system. For each specimen the bone density in 12
      regions of interest was measured. RESULTS: Besides the macroscopic examination of
      the plastinated specimens, a bone density analysis based on x-ray films is
      presented. Lowest bone density was found at the lateral wall of the sphenoid
      sinus (3.31 +/- 0.99 mm aluminum [Al]); highest density was measured at the roof
      of the sphenoid sinus (12.91 +/- 1.75 mm Al). Overall bone density in female
      specimens was 0.41 mm Al (mean) lower than in male specimens. CONCLUSIONS: This
      study is the first to use plastinated whole-organ serial sections and bone
      density images for the analysis of potential complications in ESS. The
      illustration of regions with minor and major bone density of the paranasal
      sinuses and the ethmoid floor as presented in this study may help the novice
      sinus surgeon to minimize the risks of ESS and to avoid severe complications.

PMID- 10089966
TI  - Inhibitory effect of erythromycin on interleukin-8 secretion from exudative cells
      in the nasal discharge of patients with chronic sinusitis.
AB  - OBJECTIVES: The mechanism of the efficacy of long-term low-dose macrolide therapy
      for chronic sinusitis is not fully understood. The authors studied the inhibitory
      effect of erythromycin on interleukin-8 (IL-8) secretion from exudative cells in
      the nasal discharge of patients with chronic sinusitis. STUDY DESIGN AND METHODS:
      Exudative cells in the nasal discharge were isolated from six patients with
      nonallergic chronic sinusitis. The cells, more than 90% of which were
      neutrophils, were incubated with or without erythromycin in the presence of 10
      micrograms/mL of lipopolysaccharide. The IL-8 concentrations in the culture
      supernatants were measured by enzyme-linked immunoassay. RESULTS: The amount of
      secreted IL-8 in the absence of erythromycin was 682 +/- 226 pg/10(6) cells/24 h.
      The IL-8 secretion was significantly reduced to 66 +/- 15% and 46 +/- 13% of the
      control in the presence of 10(-6) and 10(-5) M of erythromycin, respectively.
      CONCLUSION: Erythromycin may act as a biologic modulator that inhibits IL-8
      secretion from exudative cells and thereby blocks the vicious circle of
      neutrophil recruitment and IL-8 generation in the inflammatory site in chronic
      sinusitis.

PMID- 10089967
TI  - Body mass index less than 28 kg/m2 is a predictor of subjective improvement after
      laser-assisted uvulopalatoplasty for snoring.
AB  - OBJECTIVE/HYPOTHESIS: To investigate whether body mass index (BMI) can be used to
      predict subjective improvement of snoring after laser-assisted uvulopalatoplasty
      (LAUP). STUDY DESIGN: One hundred nineteen consecutive adult patients who had
      LAUP performed for socially disruptive snoring were contacted by mail 3 months
      after surgery and asked to complete a questionnaire with the following
      alternatives as to the effect of surgery on their snoring: no improvement (1);
      some improvement (2); moderate improvement (3); substantial improvement (4) and
      abolished snoring (5). Patients reporting to categories 3, 4, or 5 were referred
      to as responders and to categories 1 or 2 as nonresponders. Seventy patients
      (59%) completed the questionnaire. METHODS: A one-stage LAUP was performed with
      local anesthesia in an outpatient ear, nose, and throat clinic with a CO2 laser.
      Patients were divided into two categories with BMI above and below 28 kg/m2 at
      the time of surgery. RESULTS: BMI correlated significantly with subjective
      postoperative improvement. (R = 0.29; P < .02; Pearson's correlation test). Odds
      ratio (OR) for success by BMI less than 28 kg/m2 compared to patients with BMI
      greater than 28 kg/m2 was 4.8 (95% confidence interval [CI]: 1.48-15.53).
      CONCLUSIONS: BMI is a simple, yet important predictor of subjective reduction of
      snoring after LAUP and should be considered before performing such surgery.

PMID- 10089968
TI  - CO2 laser endoscopic posterior partial transverse cordotomy for bilateral
      paralysis of the vocal fold.
AB  - OBJECTIVE/HYPOTHESIS: A clinical evaluation of CO2 laser endoscopic posterior
      partial transverse cordotomy (EPPTC) in patients with severely compromised airway
      due to bilateral paralysis of the vocal fold. STUDY DESIGN: An inception cohort
      of 25 patients over a 10-year period. METHODS: The CO2 laser EPPTC was unilateral
      in 15 patients and bilateral in 10. Variables were tested for potential
      statistical relation to successful rehabilitation of the airway. RESULTS: The use
      of the CO2 laser never resulted in adverse side effects. Complications were not
      encountered. A one-step, successful restoration of the airway was achieved in 68%
      (17/25) of patients. In univariate analysis, the CO2 laser EPPTC was
      statistically more likely to be successful if bilateral EPPTC was performed (P =
      .018). None of the following variables--age, sex, cause of bilateral paralysis,
      prior treatment, laser parameters, and duration of postoperative antibiotherapy
      and oral steroids--was statistically related to a successful restoration of the
      airway. Revision CO2 laser EPPTC, performed in six patients, resulted in an
      overall 92% (23/25) rate for a successful restoration of the airway. The overall
      tracheotomy rate was 8% (2/25). CONCLUSION: The authors' data confirm the safety,
      ease of performance, and efficiency of the CO2 laser EPPTC in patients with
      bilateral vocal fold paralysis. This report also suggests that the completion of
      bilateral CO2 laser EPPTC statistically increases the likelihood of restoring the
      airway in a one-step surgical procedure.

PMID- 10089969
TI  - Effects of medialization laryngoplasty on airway resistance: a pilot study.
AB  - OBJECTIVE: To investigate the effects of medialization laryngoplasty on laryngeal
      airway resistance at various clinically relevant flow rates. STUDY DESIGN: This
      study was conducted using a total of 13 laboratory experiments. Two of the
      experiments were used to validate the cadaveric model employed. Eleven
      experiments were used to quantify airway resistance relative to increasing
      medialization laryngoplasty stent size. METHODS: With autopsy consent the authors
      obtained 13 consecutive and anatomically complete larynges for experimentation. A
      thyrotomy window measuring 8 x 6 mm was made on the left side of the thyroid
      cartilage. A #4 laryngeal mask was secured to the pharyngeal airway with sutures.
      Eleven experiments were conducted at the same flow rates using increasingly
      larger stents from 1 mm to 11 mm in size. Using the Bernoulli equation, the
      pressure measured at the proximal end of the laryngeal mask is representative of
      the pressure drop across the airway. The experimental model was validated in two
      experiments using flow rates between 5 and 50 L/min and stents measured at 5, 10,
      15, and 20 mm. RESULTS: Average results from the 11 experiments indicate that at
      increasing levels of medialization, from 0 to 11 mm, there is essentially the
      same pressure drop across the larynx at a given flow rate. CONCLUSION: At
      physiologic airflow rates in a cadaveric model, medialization laryngoplasty
      implants of 11 mm or less seem to have no obvious effect on airway resistance.

PMID- 10089970
TI  - Phonation threshold pressure measurements during phonation by airflow
      interruption.
AB  - OBJECTIVE/HYPOTHESIS: Most methods to measure phonation threshold pressure (PTP)
      are clinically impractical because they are invasive. This report concerns an
      airflow interruption system developed to allow noninvasive estimation of (PTP) at
      different levels of vocal intensity. An estimation of PTP was made for normal
      subjects with normal larynges and no voice complaints and for individuals who had
      dysphonia associated with vocal polyps to compare the estimated minimal pressure
      across the glottis that was required to sustain phonation in the two conditions.
      STUDY DESIGN: This was a methodological study designed to measure an
      unanticipated PTP from a subject. METHODS: Subjects sustained a constant tone and
      the airflow was directed into a section of pipe with an airtight mask over the
      mouth and nose. The airflow, intramask pressure, and intensity of the acoustic
      output were recorded. A PTP was predicted from a difference between an estimate
      of the subglottal pressure and the vocal tract pressure at the point that
      phonation ceased after interruption of airflow. Eleven control subjects and 13
      patients with vocal fold polyps were studied. In each population there were eight
      men and five women. The individuals in the group with vocal fold polyps averaged
      39 years of age, and the control subject group averaged 49 years of age. Normal
      subjects produced a steady vowel /a/ at 75, 80, and 85 dB. Patients with polyps
      were unable to sustain phonation at these levels but were able to produce
      phonation at 65, 70, and 75 dB. The validity of the system was tested using a
      laryngeal model and in a patient with a normal larynx and voice who had a
      tracheotomy (placed for sleep apnea syndrome) which allowed direct measurement of
      subglottal pressure. RESULTS: The measured mean PTP levels (with standard
      deviation [SD]) for the control subjects were 2.38 (1.273), 2.67 (1.879), and
      2.98 (2.23) cm H2O at 75, 80, and 85 dB, respectively. The measured mean PTP
      levels (with SD) for the patients with polyps were 4.79 (2.67), 5.85 (2.34), and
      7.37 (3.26) cm H2O at 75, 80, and 85 dB, respectively. The differences in mean
      PTP between groups at 75, 80, and 85 dB were significant at P = .013, P = .017,
      and P = .010, respectively. CONCLUSIONS: The estimations of PTP for patients with
      vocal fold polyps were significantly higher than for the control subjects at
      three phonation levels.

PMID- 10089971
TI  - A retrospective study of contact granuloma.
AB  - OBJECTIVES: This study evaluates the clinical features of contact granuloma and
      compares the results of voice therapy in operated versus unoperated cases. STUDY
      DESIGN: Retrospective review of 123 patients with contact granuloma. Thirty-six
      patients had undergone one or more surgeries before phoniatric consultation.
      After their final operation, 33 patients had recurrence. The three patients who
      were cured by operation were not studied further. The course of disease in the 33
      patients with recurrence was compared with that of 87 patients who did not have
      surgery. METHODS: The hospital records were reviewed concerning age, sex,
      symptoms, side of granuloma, and outcome of treatment. RESULTS: The predominant
      symptoms were vocal fatigue, vocal discomfort, the need for excessive throat
      clearing, and hoarseness. The recurrence rate after operation was 92%. Twelve
      months after voice therapy, 35% of the operated group and 51% of the unoperated
      group were cured. The patients who had surgery had almost twice as many sessions
      of voice therapy as the unoperated group, and their mean recovery time was 17
      months, compared with 8 months for the unoperated group. CONCLUSIONS: The
      recurrence rate after surgery was high. Surgery may prolong the recovery time.
      Subjective symptoms diminished during voice therapy, but we cannot confirm that
      it was beneficial for the healing process.

PMID- 10089972
TI  - Effect of pharyngeal stimulation on the motor function of the esophagus and its
      sphincters.
AB  - OBJECTIVE/HYPOTHESIS: Sensory impulses from the pharynx induce contraction of the
      upper esophageal sphincter (UES), relaxation of the lower esophageal sphincter
      (LES), and inhibition of peristalsis. To determine 1) the magnitude of UES
      contractile response to threshold volume of fluid that induces LES relaxation and
      2) the effect of rapid pharyngeal air stimulation on LES resting pressure and its
      concurrent influence on the UES and progression of esophageal peristalsis.
      METHODS: Eleven healthy volunteers (age, 31 +/- 2 y) were studied by concurrent
      UES, esophagealbody, and LES manometry. RESULTS: At a threshold volume of 0.3 +/-
      0.05 mL, injections of water into the pharynx directed posteriorly, resulted in
      complete LES relaxation. Duration of these relaxations averaged 19 +/- 1 seconds.
      In 10 of 11 subjects, these relaxations were accompanied by a simultaneous
      increase in UES resting tone that averaged 142% +/- 27% above preinjection
      values. Pharyngeal stimulation by rapid air injection resulted in complete LES
      relaxation in 8 of the 11 subjects (threshold volume, 14 +/- 6 mL). Five of 8
      developed a concurrent mild increase in resting UES pressure (17% +/- 6% above
      preinjection values) (P < .05). Pharyngeal water injection inhibited the
      progression of the peristaltic pressure wave at all tested sites and in all
      subjects, but pharyngeal air injection in only 2 of the 11 studied subjects.
      CONCLUSIONS: The inhibitory effect of pharyngeal water injection on LES resting
      pressure is accompanied by a substantial contractile effect on the UES. Although
      stimulation of the pharynx by rapid air injection may induce LES relaxation, its
      inhibitory effect on esophageal peristalsis and stimulatory effect on UES
      pressure are negligible compared with that of water injection.

PMID- 10089973
TI  - Fourth branchial arch sinus: clinical presentation, diagnostic workup, and
      surgical treatment.
AB  - OBJECTIVES/HYPOTHESIS: Abnormalities of the fourth branchial arch are much less
      common than those of the second arch and present in a different manner. The
      authors report their experience with five cases of fourth arch sinuses. METHODS:
      Retrospective chart review of patients at a tertiary care center. RESULTS: All
      patients presented in the first or second decade of life, and all but one had
      left-sided neck involvement. Four patients presented with recurrent low neck
      inflammatory episodes, and one with respiratory compromise. Diagnostic studies
      performed included ultrasound, computed tomography (CT) scan, barium swallow,
      magnetic resonance imaging, and fine-needle aspiration. Barium contrast studies
      and CT scan were the most useful in demonstrating a fourth arch sinus tract
      preoperatively. Surgical treatment with an emphasis on complete exposure of the
      recurrent laryngeal nerve and exposure of the lateral piriform sinus to
      facilitate complete sinus tract excision was successful in all patients.
      CONCLUSION: The clinical history of recurrent low neck inflammatory episodes in
      young patients, especially on the left side, should raise the suspicion of this
      entity. Investigation using barium swallow in combination with CT scanning is
      useful. Excision of the sinus tract taking care not to injure the recurrent
      laryngeal nerve is curative.

PMID- 10089974
TI  - Combined intratumor cisplatinum injection and Nd:YAG laser therapy.
AB  - OBJECTIVES/HYPOTHESIS: Interstitial laser therapy (ILT) has become useful for
      tumor palliation in patients with advanced head and neck cancer. Cisplatinum
      chemotherapy also is a frequent adjuvant treatment for recurrent tumors, but
      systemic toxicity limits application. Intratumor cisplatinum injection combined
      with ILT may improve therapy of these recurrent tumors with reduced toxicity.
      STUDY DESIGN: Prospective. Tumor transplants were injected with cisplatinum in a
      gel implant before ILT to evaluate treatment response and toxicity in a
      preclinical study. METHODS: UCLA-P3 human squamous cell carcinoma tumors were
      grown as subcutaneous transplants in nude mice and treated by intratumor
      injection of 2 mg/mL cisplatinum in a slow-release, collagen-based gel carrier 4
      hours before interstitial implantation of Nd:YAG laser fiberoptics to induce
      local tumor hyperthermia. Treatment efficacy and toxicity were followed for 12
      weeks after combined drug and laser therapy compared with ILT alone. RESULTS:
      Combined cisplatinum gel and ILT was a significant improvement (P < .01 by chi
      square test) and induced 57% complete responses without regrowth in 21
      transplanted tumors compared with only 24% in 21 tumors after ILT alone during 12
      week follow-up. Recurrences in both cases appeared to result from nonuniform
      laser energy delivery within tumors via the implanted fiberoptic tip.
      CONCLUSIONS: The results of this experimental combined cisplatinum and ILT study
      suggest it may be possible to improve treatment of advanced head and neck cancer
      by intratumor injection of gel implants containing the drug followed by
      interstitial Nd:YAG laser hyperthermia.

PMID- 10089975
TI  - Prognostic significance of p53 gene mutations in laryngeal cancer.
AB  - OBJECTIVE/HYPOTHESIS: We examined whether p53 gene mutations were predictive of
      clinical behavior in laryngeal cancer. STUDY DESIGN: Retrospective study of 45
      patients with laryngeal cancer from 1985 to 1997. METHODS: DNA was extracted from
      tumor tissue and subject to polymerase chain reaction single-strand
      conformational polymorphism (PCR-SSCP) as well as DNA sequencing. The clinical
      outcome was correlated to the presence or absence of a p53 mutation. RESULTS: The
      p53 gene was analyzed by direct DNA sequencing and was found to be mutated in 33%
      (15/45) of patients. The presence of a p53 mutation was associated with a
      significant improvement in overall survival (80% vs. 43%, P < .03) and a trend
      toward improved disease-free survival (87% vs. 60%, P = .08). When other
      prognostic factors were adjusted, multivariate analysis revealed a trend toward
      improvement in overall survival as well as disease-free survival. CONCLUSION:
      Depending on the location of a p53 mutation, the suppressive functions or
      clinical outcome may or may not be affected. Fifty-three percent of mutations
      were detected in nonconserved regions as opposed to 17% as reported in colon
      cancer. In colon cancer, mutations in conserved regions of the p53 gene predicted
      a poorer survival, whereas nonconserved gene mutations were not predictive. In
      our group of patients. p53 mutations predicted a better prognosis, which may be
      due to a large proportion of mutations that lie within nonconserved areas. The
      predictive power of p53 gene mutations may depend on functional loss and
      inactivation of highly conserved areas and must be tested in a prospective trial.

PMID- 10089976
TI  - Preoperative permanent balloon occlusion of internal carotid artery in patients
      with advanced head and neck squamous cell carcinoma.
AB  - OBJECTIVE/HYPOTHESIS: To determine the value of preoperative balloon occlusion in
      predicting the safety of carotid artery resection in advanced recurrent head and
      neck squamous cell carcinoma. STUDY DESIGN: Retrospective chart review of all
      cases undergoing planned carotid artery resection for recurrent disease at a
      major university hospital. METHODS: If the carotid artery was encased, a
      nonemergent carotid artery balloon test occlusion was performed for 30 minutes.
      If the patient tolerated this, he or she underwent permanent carotid artery
      occlusion. RESULTS: Twenty-three patients were prospectively evaluated for
      resection. Three underwent emergent carotid artery ligation. Twenty others
      underwent nonemergent carotid artery test occlusion. Of these, 5 patients failed
      preoperative carotid artery balloon occlusion and 15 patients successfully
      underwent permanent carotid balloon occlusion. Although eight of these patients
      died of recurrent disease in less than 1 year, seven patients survived more than
      1 year with two patients surviving more than 2 years. CONCLUSIONS: Preoperative
      carotid balloon occlusion predicted patients who could tolerate permanent
      occlusion. All patients eventually developed recurrent disease, but in 14 of the
      15 patients, no hemorrhages occurred.

PMID- 10089977
TI  - Upper neck (level II) dissection for N0 neck supraglottic carcinoma.
AB  - OBJECTIVES: Elective neck dissection for the N0 neck in head and neck surgery is
      still controversial. This prospective nonrandomized study of N0 supraglottic
      carcinoma was designed to find an appropriate method of neck management. STUDY
      DESIGN: Anatomical studies show that the first echelon of lymphatic drainage from
      the supraglottic larynx is toward the upper jugular nodes (level II). An upper
      neck dissection (UND) was applied and all the lymph nodes were sent for frozen
      section. If the subclinical metastasis was found, a modified neck dissection was
      performed. If the nodes harbored no foci of cancer, the patients were observed
      after surgery on the supraglottic lesions. METHODS: Patient records of 142
      patients with supraglottic laryngeal cancer (T1-4N0M0) were reviewed, with
      special attention paid to neck recurrences and survival rates. The cases were
      treated between 1976 and 1990 and all were observed for at least 5 years after
      the operation or until the time of death. RESULTS: The UND specimens of 142
      patients were negative for metastasis. The 5-year survival rate for this group
      after surgery was 80.8%, according to the life table analysis. Fifteen of the 142
      patients (10.6%) had neck recurrences during the period of observation within 5
      years. The recurrence rate of this series with limited dissection on the neck was
      comparable with those reported in the literature after neck dissection, either
      radical or modified. CONCLUSIONS: There is no need for a comprehensive neck
      dissection for N0 supraglottic laryngeal cancer. A selective neck dissection such
      as UND (level II) or a supraomohyoid neck dissection (sparing the submandibular
      region) of level II and III will serve the purpose of radical neck treatment for
      the supraglottic cancer.

PMID- 10089978
TI  - Evidence of mast cell activity in the middle ears of children with otitis media
      with effusion.
AB  - OBJECTIVES: This is the first study to report the presence of tryptase, a
      reflection of mast cell activity, in chronic middle ear effusion of patients
      whose atopic status was characterized. DESIGN AND METHODS: Mediator activity of
      mast cells and eosinophils was measured prospectively from effusion of 33
      randomly selected patients and 5 control subjects with chronic otitis media with
      effusion (OME). Atopy was determined by enzyme-linked immunosorbent assay. Middle
      ear biopsies from a second group of 8 OME patients and 4 controls were fixed in
      plastic and stained immunohistochemically for mast cells. RESULTS: Sixty-one
      percent of patients had extensive activation of mast cells in their middle ears.
      Among those with elevated tryptase in their effusion, 95.6% were atopic and 94.7%
      also had elevated levels of effusion eosinophilic cationic protein (ECP).
      Tryptase levels were elevated only in the effusion of atopic patients, as
      compared with 5 controls (P < .01). Mast cells were present in 6 of 8 OME ears
      and absent in all 4 normal ears. CONCLUSION: Mast cells and its mediator
      tryptase, both indicators of a Th2-driven immune response, are present in a
      majority of ears that have chronic effusion. These findings support the
      hypothesis that middle ear mucosa is capable of an allergic response and that the
      inflammation within the middle ear of most OME patients is allergic in nature.

PMID- 10089979
TI  - A technique of mastoidectomy and meatoplasty that minimizes factors associated
      with a discharging mastoid cavity.
AB  - OBJECTIVES: To present and assess a surgical technique designed to minimize the
      known causes of a discharging mastoid cavity. STUDY DESIGN: A temporal bone
      dissection to establish the anatomical relationships on which the surgical
      technique is based. A presentation of the proposed surgical technique and a
      prospective assessment of the technique in twenty consecutive mastoidectomies.
      METHODS: Five temporal bone dissections were performed to establish the
      relationship between the chorda tympani and the facial nerve when these
      structures are approached from above. The surgical technique is presented and the
      mastoid cavities of twenty consecutive patients assessed. The assessment included
      measurement of the facial ridge height, "kidney-shape" of the cavity, size of the
      cavity, size of the meatus, and state of the tympanic membrane. RESULTS: In the
      temporal bone dissections the vertical height between the chorda tympani and the
      facial nerve at 3/9 o'clock was a mean of 2.01 mm. Nineteen of the 20 consecutive
      mastoid cavities (95%) performed with the presented technique remained well
      healed and dry. The mean facial ridge height was 2.7 mm at 3/9 o'clock and 4.8 mm
      at 6 o'clock. The kidney-shaped measurement was 1.45 mm. The mean size of the
      cavities was 2.6 mm and 18 of the 20 patients (90%) had an intact tympanic
      membrane. The mean largest diameter of the meatus was 10.1 mm. CONCLUSIONS: The
      surgical technique presented produces a mastoid cavity with a low facial ridge
      and oval shape. These two factors have been previously identified as important in
      the outcome of mastoid surgery.

PMID- 10089980
TI  - Otogenic intracranial infections in adults.
AB  - OBJECTIVE: To assess the type and bacteriology of otologic diseases associated
      with bacterial meningitis in adults. METHOD: Retrospective review of 79 patients
      over an 18-year period. RESULTS: Acute otitis media was diagnosed in 32 patients,
      chronic otitis in 29 (16 with cholesteatoma), and cerebrospinal fluid leak in 18.
      Streptococcus pneumoniae was a common cause of meningitis-complicating acute
      otitis media (69%) or cerebrospinal fluid leak (50%), whereas other bacteria or
      negative cultures were found in the cerebrospinal fluid of patients with chronic
      otitis. Surgery was performed promptly in 26 patients; four patients died.
      CONCLUSIONS: Early diagnosis of otogenic bacterial meningitis is essential to
      allow appropriate antimicrobial treatment. Antimicrobials active on gram negative
      bacilli and anaerobes should be used in patients with chronic otitis. An
      emergency surgical procedure is required in patients whose neurologic or
      infectious status fails to improve under antimicrobial treatment.

PMID- 10089981
TI  - Fibro-osseous lesions of the external auditory canal.
AB  - OBJECTIVES: To differentiate a novel type of benign circumscribed bone lesion of
      the external auditory canal from those described previously, such as exostoses
      and osteomas. STUDY DESIGN: Information was obtained from computed tomography
      (CT) images, surgical findings, and pathologic study. METHODS: Five patients (26
      to 82 years old) who presented a hard, round, unilateral, skin-covered mass
      occluding the external auditory canal to varying degrees were studied. A CT study
      carried out before resection of the lesions by curettage disclosed the absence of
      a bony connection to the underlying structures. All the tissue specimens
      underwent pathologic study. RESULTS: CT and surgical findings demonstrated the
      absence of a connective pedicle. The pathologic findings showed lesions
      consisting of an osteoma-like bone formation with sparse osteoblastic areas;
      mature lamellar bone was observed in three cases, bone marrow containing adipose
      tissue and hematopoietic remnants in two, and a dense, collagenous stroma in
      another. They all showed irregular trabeculae, bordered by osteoid osteoblasts.
      In no case was there evidence of a relationship to the cartilaginous tissue or to
      the bony structures of the external auditory canal. CONCLUSIONS: The data
      obtained from the clinical, CT, surgical, and pathologic findings suggest the
      existence of a lesion unlike those previously known, possibly related to
      ossifying reactions in other parts of the organism.

PMID- 10089982
TI  - A clinical study on the magnetic stimulation of the facial nerve.
AB  - OBJECTIVES: A clinical study on the usefulness of magnetic stimulation of the
      facial nerve, with special attention paid to the selection of the coil shape and
      stimulation procedures. STUDY DESIGN: The subjects consisted of 55 patients with
      Bell's palsy, 1 patient with a cerebellopontine angle (CPA) tumor, 1 patient with
      multiple sclerosis (MS), and 30 normal subjects. Three types of coils were used
      in this study; a 90-mm large single coil, a 40-mm small single coil, and a 20-mm
      small double coil. METHODS: The compound muscle action potentials (CMAPs) and
      long latency response were evoked by transcranial magnetic stimulation (TMS) with
      a 90-mm large single coil. The 40-mm small single coil was used to test blink
      reflex by aiming it at the supraorbital nerve as the target site. The
      subcutaneous activation of the infra-auricular facial nerve was performed with
      the 20-mm double coil. RESULTS: The reproducible CMAP and long latency responses
      were obtained from normal subjects with TMS. However, responses were observed
      only in patients with relatively mild Bell's palsy. The magnetic stimulation
      evoked responses reflected the brainstem function in the patients with a CPA
      tumor and MS. CONCLUSION: Although magnetic stimulation remains inferior to
      conventional electric stimulation in some sense and requires further study, this
      method is potentially useful because it can stimulate the facial nerve
      continuously from the cortex to the periphery and can effectively evoke responses
      reflecting the brainstem function.

PMID- 10089983
TI  - Middle ear pathologic changes associated with chronic anaerobic sinusitis in
      rabbits.
AB  - OBJECTIVE/HYPOTHESIS: To study the histopathologic changes in association with
      the inflammatory/immune response present in the middle ears of a rabbit model of
      unilateral chronic anaerobic sinusitis. STUDY DESIGN: New Zealand white rabbits,
      two at each experimental time point. Normal rabbits and sham-operated animals
      served as controls. METHODS: Left maxillary sinusitis was induced by inoculating
      Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages,
      and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2,
      3, and 4 weeks following inoculation. Parameters analyzed include tissue for
      histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and
      lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN
      gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture.
      RESULTS: Despite closure of the ostium of the left sinus, mild to moderate
      dissemination of B fragilis into the right sinus and left and right ears were
      observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively).
      Histopathologic changes in the right sinus and middle ears were much less severe
      in contrast to the severe inflammatory changes in the left sinus. An immune
      response against B fragilis appeared to occur in the sinuses and ears bilaterally
      independent of bacterial dissemination, as evidenced by a rise of IgG Ab in
      lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated
      animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated
      rabbits, the magnitude of IgG Ab responses was equivalent in the right and left
      ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear
      positively correlated to each other (P < .01) and to the levels in the sinuses (P
      < .01 and P < .01). LDH levels were closely associated with bacterial growth and
      degree of tissue inflammation. CONCLUSION: This reproducible model of chronic
      sinusitis provides an opportunity to study the middle ear infection and
      inflammatory/immune responses occurring with sinusitis. Our results indicate
      bilateral middle ear mucosal immune responses to an elicited sinus infection,
      independent of B fragilis dissemination.

PMID- 10089984
TI  - Autologous transplantation of fascia into the vocal fold: a new phonosurgical
      technique for glottal incompetence.

PMID- 10089985
TI  - Endoscopic transseptal transsphenoidal hypophysectomy with three-dimensional
      intraoperative localization technology.

PMID- 10089986
TI  - Dr. William Worrall Mayo and the Minnesota Territory.

PMID- 10089987
TI  - Type 1 diabetes mellitus in early childhood: glycemic control and associated risk
      of hypoglycemic reactions.
AB  - OBJECTIVE: To assess the level of glycemic control and to determine whether more
      normal glycemic control, as measured by glycosylated hemoglobin, leads to
      frequent hypoglycemic episodes in young patients with type 1 diabetes mellitus.
      MATERIAL AND METHODS: We undertook a retrospective review of the medical records
      of 59 children with type 1 diabetes diagnosed at age 9 years or younger, who
      underwent follow-up at our institution for at least 2 years. For each follow-up,
      insulin requirements, levels of glycosylated hemoglobin, and frequency of
      hypoglycemic reactions were analyzed for three age-groups--0 to 2 years, 2 to 5
      years, and 5 to 9 years old. RESULTS: The mean glycosylated hemoglobin for the
      first 2 years after diagnosis of type 1 diabetes was higher in children 0 to 2
      years old in comparison with the other age-groups. This increased glycosylated
      hemoglobin occurred despite increased administration of insulin, expressed in
      units per kilogram daily, to these children (P < 0.05). Severe hypoglycemic
      reactions were more common in infants (55%) and children between 2 and 5 years
      old (45%) than in children from 5 to 9 years old (13%). In all age-groups, the
      mean glycosylated hemoglobin value closest to a hypoglycemic event and the mean
      glycosylated hemoglobin value for the 2-year study period were similar but were
      both less than 8% (the standard established by the Diabetes Control and
      Complications Trial). Most reactions had no clear cause in the youngest age
      group, whereas a specific reason could usually be determined in children 2 to 5
      years old. CONCLUSION: Tight glycemic control is achievable in young patients
      with type 1 diabetes mellitus. Such tight control, however, may lead to an
      increase in the frequency of severe hypoglycemic reactions in this patient
      population. Our data support the guideline that children younger than 5 years
      should have a higher goal for premeal plasma glucose levels.

PMID- 10089988
TI  - Survival of home parenteral nutrition-treated patients: 20 years of experience at
      the Mayo Clinic.
AB  - OBJECTIVE: To present the largest single institutional review of demographics,
      associated primary diseases, and survival of patients receiving home parenteral
      nutrition (HPN). MATERIAL AND METHODS: We conducted a retrospective review of
      medical records of all Mayo Clinic patients treated with HPN between 1975 and
      1995. The probability of survival was calculated by using Kaplan-Meier analysis.
      RESULTS: In the 225 study patients requiring HPN (median age, 51 years), the main
      underlying primary diseases were as follows: inflammatory bowel disease (IBD) (N
      = 50), nonterminal active cancer (N = 39), ischemic bowel (N = 35), radiation
      enteritis (N = 32), motility disorder (chronic pseudo-obstruction) (N = 26), and
      adhesive intestinal obstruction (N = 18). Other conditions included intestinal
      and pancreatic fistula, refractory sprue, dumping syndrome, and protein-losing
      enteropathy. The overall probability of 5-year survival during HPN was 60%. The
      probability of survival at 5 years based on the primary disease was 92% for IBD,
      60% for ischemic bowel, 54% for radiation enteritis, 48% for motility disorder,
      and 38% for cancer. The probability of 5-year survival stratified by age at
      initiation of HPN was as follows: younger than 40 years, 80%; 40 through 60
      years, 62%; and older than 60 years, 30%. Most deaths during therapy with HPN
      were attributable to the primary disease. Among the 20 patients who died of an
      HPN-related cause, 11 deaths were from catheter sepsis, 4 from liver failure, 2
      from venous thrombosis, and 2 from metabolic abnormalities. CONCLUSION: Survival
      of HPN-treated patients is best predicted on the basis of the primary disease and
      the age at initiation of HPN. Patients with IBD and age younger than 40 years
      have a better 5-year survival in comparison with other groups. Most deaths during
      treatment with HPN are a result of the primary disease; HPN-related deaths are
      uncommon.

PMID- 10089989
TI  - Clinical assessment and outcome in 70 patients with complaints of burning or sore
      mouth symptoms.
AB  - OBJECTIVE: To review a series of patients with a burning or sore mouth for
      elucidation of associated conditions and treatment outcome. MATERIAL AND METHODS:
      We retrospectively studied 70 consecutive patients with a burning or sore mouth
      who were encountered at a tertiary-care center between 1979 and 1992. Clinical
      and laboratory findings were summarized, and follow-up data were analyzed.
      RESULTS: The study cohort of 56 women and 14 men had a mean age of 59 years. They
      had had a burning or sore mouth for a mean duration of 2.5 years. Multiple
      etiologic factors for the burning or sore mouth were present in 37% of the study
      subjects. The most frequently associated conditions were psychiatric disease
      (30%), xerostomia (24%), geographic tongue (24%), nutritional deficiencies (21%),
      and allergic contact stomatitis (13%). With a treatment course tailored to the
      suspected causal factor, 72% of the patients who had follow-up reported
      improvement. CONCLUSION: With a directed investigation, one or more causes could
      be identified in most patients who had a burning or sore mouth. Successful
      management of these symptoms was possible in a majority of the patients.

PMID- 10089990
TI  - Grover's disease: clinicopathologic review of 72 cases.
AB  - OBJECTIVE: To report the clinicopathologic findings in patients with Grover's
      disease. MATERIAL AND METHODS: We reviewed the medical records and biopsy
      specimens from 72 patients with transient acantholytic dermatosis (Grover's
      disease) examined at Mayo Clinic Rochester. Hematoxylin-eosin-stained biopsy
      specimens (from all patients) were assessed. Immunohistochemistry stains BRST-2,
      CAM 5.2, and CD44 were used to stain eight specimens. Direct immunofluorescence
      reports were reviewed. Selected specimens were stained by indirect
      immunofluorescence to detect major basic protein. RESULTS: Of the 72 patients, 63
      (88%) were men, and the mean age was 48 years (range, 31 to 85). Lesions were
      distributed mainly on the trunk (in 71 patients) and proximal extremities (in
      25). Heat and sweating frequently were exacerbating factors. Fifteen patients
      (21%) were bedbound. Concurrent nondermatologic malignant disease was present in
      18 patients (25%). Two patients (3%) had acquired immunodeficiency syndrome.
      Follow-up in 28 patients (mean, 38 months; range, 3 months to 7 years) revealed
      that the disease had recurred in 13, persisted in 3, and resolved in 12. Review
      of the biopsy specimens showed that acantholysis was pemphigus vulgaris-like in
      40 patients (56%), Darier's disease-like in 16 (22%), spongiotic in 12 (17%),
      pemphigus foliaceus-like in 2 (3%), and Hailey-Hailey disease-like in 2 (3%). A
      perivascular lymphocytic infiltrate of varied intensity in 64 specimens (89%) was
      associated with eosinophils in 16 (22%). In nine biopsy specimens with dermal
      eosinophilia stained for major basic protein, varied dermal cellular and
      extracellular deposition of major basic protein was present. Results of direct
      immunofluorescence studies, performed in 17 cases, were negative or nonspecific.
      CD44 stained acantholytic areas in addition to sweat glands in two of eight
      specimens (25%). CONCLUSION: Further studies of the pathogenesis of Grover's
      disease are needed. The predisposing conditions, site of involvement, and
      relapsing nature of this disorder may implicate acrosyringeal dysfunction as the
      cause.

PMID- 10089991
TI  - Myocardial infarction complicating gastrointestinal hemorrhage.
AB  - OBJECTIVE: To determine the frequency of and risk factors for myocardial
      infarction (MI) in patients admitted to an intensive-care unit (ICU) with
      gastrointestinal (GI) hemorrhage and to ascertain the effects on mortality and
      lengths of stay. MATERIAL AND METHODS: Demographic, laboratory, and outcome data
      were determined for all patients admitted to a medical ICU with GI hemorrhage
      between April 1996 and January 1997. Serial creatine kinase with isoenzyme levels
      and electrocardiograms were interpreted blindly by a senior cardiologist.
      RESULTS: For 83 consecutive admissions to the ICU because of GI hemorrhage, the
      patients' mean (+/- standard error) age was 65.0 +/- 1.7 years and APACHE II
      (acute physiology and chronic health evaluation) score was 15.7 +/- 0.8. In
      hospital death occurred in 16 patients (19%). Patients who did not survive had a
      lower admission systolic blood pressure (99.2 +/- 4.5 versus 115.0 +/- 4.0 mm Hg;
      P = 0.01) than did those who survived. Eleven of 83 patients (13%) fulfilled both
      enzymatic and electrocardiographic criteria for MI. Ten patients (12%) had
      electrocardiographic evidence of myocardial ischemia but did not meet criteria
      for MI. Patients with MI were older (74.4 +/- 4.0 versus 61.7 +/- 2.0 years; P <
      0.05), had a higher acuity of illness (APACHE II score, 21.6 +/- 3.0 versus 14.6
      +/- 0.7; P < 0.05), and had more coronary risk factors (2.3 +/- 0.3 versus 1.4 +/
      0.1; P < 0.05) in comparison with those without MI or ischemia. Patients with MI
      also had longer ICU (8.6 +/- 2.4 versus 3.3 +/- 0.4 days; P < 0.05) and hospital
      (16.3 +/- 3.4 versus 9.1 +/- 0.8 days; P < 0.05) lengths of stay. Patients older
      than 65 years had a threefold increased risk (risk ratio, 4.0; 95% confidence
      interval, 0.9 to 17.4) and those with two or more risk factors for coronary
      artery disease had a ninefold increased risk of MI (risk ratio, 10.2; 95%
      confidence interval, 1.4 to 76.1) in comparison with those who were younger or
      who had fewer coronary risk factors, respectively. MI complicating GI hemorrhage
      did not significantly affect the risk of in-hospital mortality (risk ratio, 1.5;
      95% confidence interval, 0.5 to 4.4). CONCLUSION: MI occurs frequently in
      patients with GI hemorrhage admitted to an ICU. Age more than 65 years and two or
      more risk factors for coronary artery disease identify patients who are at
      greatest risk for occurrence of MI, which is associated with longer ICU and
      hospital stays.

PMID- 10089992
TI  - Hermann Muller--Nobel Prize for contributions to genetics.

PMID- 10089993
TI  - Electron beam computed tomographic coronary calcium scanning: a review and
      guidelines for use in asymptomatic persons.
AB  - Coronary artery disease is the No. 1 cause of death in the developed world.
      Effective means of treatment such as drug therapy to lower cholesterol levels are
      available, but clinical application to patients at highest risk remains
      imprecise. Electron beam computed tomography (EBCT) has been suggested as a means
      to diagnose subclinical coronary disease and facilitate risk stratification, but
      no current interpretive consensus exists in clinical practice. We critically
      reviewed current, pertinent literature regarding EBCT coronary calcium scanning
      from a clinical perspective and, in particular, studies that evaluated it as a
      measure of atherosclerotic coronary disease. Additionally, we reviewed studies
      that quantified the EBCT "calcium score" in relationship to coronary heart
      disease events. The available data suggest that the EBCT calcium score can help
      identify persons at higher than anticipated risk of future coronary events: the
      greater the EBCT coronary calcium score, the greater the extent of
      atherosclerotic plaque disease. Based on the literature review, we offer EBCT
      interpretation guidelines as they relate to drug therapy and risk reduction in
      asymptomatic persons with borderline cholesterol levels. Considerable evidence
      shows that coronary calcium is specific for atherosclerotic plaque and that it
      can be sensitively detected and accurately quantified by using EBCT. The coronary
      calcium score can help guide initiation of clinical prevention programs as part
      of a risk stratification and management scheme aimed at improving outcomes in
      patients determined to be at highest risk of coronary disease for their
      respective age and gender.

PMID- 10089994
TI  - Meningioma in four patients with human immunodeficiency virus infection.
AB  - We describe four patients infected with the human immunodeficiency virus (HIV)
      who had development of meningiomas. In contrast to those in the general
      population who have meningiomas, all our patients were young men; the mean age
      was 40 years (range, 32 to 50). Their risk behavior for HIV was homosexuality
      (three patients) and intravenous drug use (one patient). The CD4+ cell count in
      each of the three homosexual men was less than 50/microL and was 280/microL in
      the drug user. Imaging studies showed enhancing lesions in three of the patients.
      Although each of these meningiomas could have occurred in otherwise normal young
      to middle-aged men, we speculate that the meningiomas may have grown in these HIV
      infected hosts because of either loss of immune function or dysregulation of
      cytokines.